US20030211611A1

US20030211611A1 - Antisense modulation of estrogen receptor alpha expression

Info

Publication number: US20030211611A1
Application number: US10/448,753
Authority: US
Inventors: Kenneth Dobie; Mark Roach
Original assignee: Individual
Current assignee: Individual
Priority date: 2001-12-18
Filing date: 2003-05-30
Publication date: 2003-11-13
Also published as: US20030139360A1; AU2002366353A8; WO2003052072A3; US6617162B2; WO2003052072A2; AU2002366353A1

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of estrogen receptor alpha. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding estrogen receptor alpha. Methods of using these compounds for modulation of estrogen receptor alpha expression and for treatment of diseases associated with expression of estrogen receptor alpha are provided.

Description

INTRODUCTION

This application is a division of U.S. Ser. No. 10/027,983 filed Dec. 18, 2001.[0001]

FIELD OF THE INVENTION

The present invention provides compositions and methods for modulating the expression of estrogen receptor alpha. In particular, this invention relates to compounds, particularly oligonucleotides, specifically hybridizable with nucleic acids encoding estrogen receptor alpha. Such compounds have been shown to modulate the expression of estrogen receptor alpha.

BACKGROUND OF THE INVENTION

Steroid, thyroid and retinoid hormones produce a diverse array of physiologic effects through the regulation of gene expression. Upon entering the cell, these hormones bind to a unique group of intracellular nuclear receptors which have been characterized as ligand-dependent transcription factors. This complex then moves into the nucleus where the receptor and its cognate ligand interact with the transcription preinitiation complex affecting its stability and ultimately, the rate of transcription of the target genes. Members of the nuclear receptor family share several structural features including a central, highly conserved DNA-binding domain which targets the receptor to specific DNA sequences known as hormone response elements (Kliewer et al., Science, 1999, 284, 757-760).

Estrogens are steroid hormones that exert a wide range of effects throughout the body. They are required for normal female sexual maturation and promote growth and differentiation of the breast, uterus, fallopian tubes, vagina and ovaries. Male reproductive tissues such as testis and prostate are also estrogen target tissues. Furthermore, estrogens are important for bone maintenance and have a protective role in the cardiovascular system. In the brain, estrogens appear to modulate the regulation and reproduction of autonomic and reproductive neuroendocrine systems, mood and cognition (Osterlund and Hurd, Prog. Neurobiol., 2001, 64, 251-267).

Similar to the other steroid hormone receptors, the estrogen receptors consist of several structural domains that exhibit different functional features. Both the estrogen receptor alpha and estrogen receptor beta consist of five different domains, the N-terminal domain (called A/B), the DNA-binding domain (C), a short hinge region (E) and a short C-terminal domain (F) (Osterlund and Hurd, Prog. Neurobiol., 2001, 64, 251-267).

Estrogen receptor alpha (also known as estrogen receptor 1, ESR1, ESR-alpha and NR3A1) was first cloned and sequenced from the MCF-7 breast cancer cell line in 1985 (Green et al., J. Steroid Biochem., 1986, 24, 77-83; Greene et al., Science, 1986, 231, 1150-1154; Walter et al., Proc. Natl. Acad. Sci. U.S.A., 1985, 82, 7889-7893). Greene et al. noted significant homology of estrogen receptor alpha to the v-erbA oncogene product (Greene et al., Science, 1986, 231, 1150-1154).

Estrogen receptors constitute the only known members of the family of steroid receptors that have multiple subtypes. The involvement of mutations and splice variants of estrogen receptor alpha in breast cancer is well known in the art (Balleine et al., J. Clin. Endocrinol. Metab., 1999, 84, 1370-1377; Fuqua et al., J. Cell Biochem., 1993, 51, 135-139; Garcia et al., Mol. Endocrinol., 1988, 2, 785-791; McGuire et al., J. Steroid Biochem. Mol. Biol., 1992, 43, 243-247; McGuire et al., Mol. Endocrinol., 1991, 5, 1571-1577; Murphy et al., J. Clin. Endocrinol. Metab., 1996, 81, 1420-1427; Scott et al., J. Clin. Invest., 1991, 88, 700-706). Additionally, splice variants of estrogen receptor alpha have been identified in pituitary tumors (Chaidarun and Alexander, Mol. Endocrinol., 1998, 12, 1355-1366; Chaidarun et al., J. Clin. Endocrinol. Metab., 1997, 82, 1058-1065; Shupnik et al., J. Clin. Endocrinol. Metab., 1998, 83, 3965-3972) and in normal endometrial tissue (Daffada and Dowsett, J. Steroid Biochem. Mol. Biol., 1995, 55, 413-421). Ye et al. have identified a novel estrogen receptor alpha/fatty acid synthase fusion transcript in a variety of human cancers including prostate, breast, cervical and bladder cancer cell lines (Ye et al., Biochim. Biophys. Acta, 2000, 1493, 373-377).

The nucleic acid sequence of estrogen receptor alpha is disclosed in U.S. Pat. No. 6,235,872 (Bredesen and Rabizadeh, 2001).

Disclosed and claimed in PCT publications WO 01/00823 and WO 01/62969 are nucleic acid molecules encoding isoforms of human estrogen receptor alpha (Gannon et al., 2001; Kalush et al., 2001). Additionally disclosed and claimed in PCT publication WO 01/00823 are nucleic acid molecules hybridizing to said nucleic acid molecules encoding estrogen receptor alpha isoforms, under stringent conditions (Gannon et al., 2001).

The involvement of estrogen receptor alpha in cell proliferation indicates that its selective inhibition may prove to be a useful target for therapeutic intervention in a variety of cancers.

Because estrogens are thought to support breast cancer, estrogen antagonists have been developed which act through the estrogen receptor. Selective estrogen receptor modulators (SERMs) are small molecules which manifest variable agonist and antagonist properties when examined in the context of estrogen-dependent responses occurring in various tissues. Examples of SERMs include raloxifene and tamoxifen (Dutertre and Smith, J. Pharmacol. Exp. Ther., 2000, 295, 431-437).

Disclosed and claimed in PCT publications WO 00/74485 and WO 99/54459 are catalytic nucleic acids (known as ribozymes), capable of modulating the expression of estrogen receptor alpha (Roy et al., 2000; Thompson et al., 1999).

Double-stranded DNA fragments containing 5′ upstream sequences of the human estrogen receptor alpha gene have been used to modulate the transcriptional activity of estrogen receptor alpha (Penolazzi et al., Breast Cancer Res. Treat., 1998, 49, 227-235).

A series of studies have employed antisense estrogen receptor alpha RNA transfections to investigate effects of downregulation of estrogen receptor alpha expression in MCF-7 human breast cancer cells (Defazio et al., Cell Growth Differ., 1997, 8, 903-911; Jeng et al., Cancer Lett., 1994, 82, 123-128; Jiang and Jordan, J. Natl. Cancer Inst., 1992, 84, 580-591; Lazennec et al., Mol. Endocrinol., 1999, 13, 969-980; Madden et al., Eur. J. Cancer, 2000, 36, S34-S35; Williard et al., Gene, 1994, 149, 21-24). In two of the aforementioned investigations, paradoxical upregulation of estrogen receptor alpha was observed (Jeng et al., Cancer Lett., 1994, 82, 123-128; Jiang and Jordan, J. Natl. Cancer Inst., 1992, 84, 580-591).

Antisense oligodeoxynucleotides have also been used to decrease levels of estrogen receptor alpha in rat brain (Inamdar et al., J. Appl. Physiol., 2001, 91, 1886-1892; McCarthy et al., Endocrinology, 1993, 133, 433-439) and in a mouse colon cancer cell line (Xu and Thomas, Mol. Cell Endocrinol., 1994, 105, 197-201).

Antisense 18-mer oligonucleotides targeting positions-117 to −99, -3 to 15 (encompassing the start codon), 302 to 320, 495 to 512, 539 to 557, 1140 to 1157 and 4134 to 4151, of estrogen receptor alpha have been used to inhibit its expression in MCF-7 human breast cancer cells (Santagati et al., Mol. Endocrinol., 1997, 11, 938-949; Taylor et al., Antisense Nucleic Acid Drug Dev., 2001, 11, 219-231). In a separate investigation, also using MCF-7 breast cancer cells, a 15-mer methylphosphonate-phosphodiester antisense oligonucleotide was used to target the start codon of estrogen receptor alpha (Madden et al., Eur. J. Cancer, 2000, 36, S34-S35).

To date, investigative strategies aimed at modulating estrogen receptor alpha expression have involved the use of small molecule SERMs, ribozymes, double-stranded DNA decoys, antisense RNA transfections and antisense oligonucleotides. There remains a long felt need for additional agents capable of effectively inhibiting estrogen receptor alpha function.

Antisense technology is emerging as an effective means for reducing the expression of specific gene products and may therefore prove to be uniquely useful in a number of therapeutic, diagnostic, and research applications for the modulation of expression of estrogen receptor alpha.

The present invention provides compositions and methods for modulating expression of estrogen receptor alpha, including modulation of spliced variants of estrogen receptor alpha.

SUMMARY OF THE INVENTION

The present invention is directed to compounds, particularly antisense oligonucleotides, which are targeted to a nucleic acid encoding estrogen receptor alpha, and which modulate the expression of estrogen receptor alpha. Pharmaceutical and other compositions comprising the compounds of the invention are also provided. Further provided are methods of modulating the expression of estrogen receptor alpha in cells or tissues comprising contacting said cells or tissues with one or more of the antisense compounds or compositions of the invention. Further provided are methods of treating an animal, particularly a human, suspected of having or being prone to a disease or condition associated with expression of estrogen receptor alpha by administering a therapeutically or prophylactically effective amount of one or more of the antisense compounds or compositions of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention employs oligomeric compounds, particularly antisense oligonucleotides, for use in modulating the function of nucleic acid molecules encoding estrogen receptor alpha, ultimately modulating the amount of estrogen receptor alpha produced. This is accomplished by providing antisense compounds which specifically hybridize with one or more nucleic acids encoding estrogen receptor alpha. As used herein, the terms “target nucleic acid”! and “nucleic acid encoding estrogen receptor alpha” encompass DNA encoding estrogen receptor alpha, RNA (including pre-mRNA and mRNA) transcribed from such DNA, and also cDNA derived from such RNA. The specific hybridization of an oligomeric compound with its target nucleic acid interferes with the normal function of the nucleic acid. This modulation of function of a target nucleic acid by compounds which specifically hybridize to it is generally referred to as “antisense”. The functions of DNA to be interfered with include replication and transcription. The functions of RNA to be interfered with include all vital functions such as, for example, translocation of the RNA to the site of protein translation, translation of protein from the RNA, splicing of the RNA to yield one or more mRNA species, and catalytic activity which may be engaged in or facilitated by the RNA. The overall effect of such interference with target nucleic acid function is modulation of the expression of estrogen receptor alpha. In the context of the present invention, “modulation” means either an increase (stimulation) or a decrease (inhibition) in the expression of a gene. In the context of the present invention, inhibition is the preferred form of modulation of gene expression and mRNA is a preferred target.

It is preferred to target specific nucleic acids for antisense. “Targeting” an antisense compound to a particular nucleic acid, in the context of this invention, is a multistep process. The process usually begins with the identification of a nucleic acid sequence whose function is to be modulated. This may be, for example, a cellular gene (or mRNA transcribed from the gene) whose expression is associated with a particular disorder or disease state, or a nucleic acid molecule from an infectious agent. In the present invention, the target is a nucleic acid molecule encoding estrogen receptor alpha. The targeting process also includes determination of a site or sites within this gene for the antisense interaction to occur such that the desired effect, e.g., detection or modulation of expression of the protein, will result. Within the context of the present invention, a preferred intragenic site is the region encompassing the translation initiation or termination codon of the open reading frame (ORF) of the gene. Since, as is known in the art, the translation initiation codon is typically 5′-AUG (in transcribed mRNA molecules; 5′-ATG in the corresponding DNA molecule), the translation initiation codon is also referred to as the “AUG codon,” the “start codon” or the “AUG start codon”. A minority of genes have a translation initiation codon having the RNA sequence 5′-GUG, 5′-UUG or 5′-CUG, and 5 ¹-AUA, 5′-ACG and 5′-CUG have been shown to function in vivo. Thus, the terms “translation initiation codon” and “start codon” can encompass many codon sequences, even though the initiator amino acid in each instance is typically methionine (in eukaryotes) or formylmethionine (in prokaryotes). It is also known in the art that eukaryotic and prokaryotic genes may have two or more alternative start codons, any one of which may be preferentially utilized for translation initiation in a particular cell type or tissue, or under a particular set of conditions. In the context of the invention, “start codon” and “translation initiation codon” refer to the codon or codons that are used in vivo to initiate translation of an mRNA molecule transcribed from a gene encoding estrogen receptor alpha, regardless of the sequence(s) of such codons.

It is also known in the art that a translation termination codon (or “stop codon”) of a gene may have one of three sequences, i.e., 5′-UAA, 5′-UAG and 5′-UGA (the corresponding DNA sequences are 5′-TAA, 5′-TAG and 5′-TGA, respectively). The terms “start codon region” and “translation initiation codon region” refer to a portion of such an mRNA or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction (i.e., 51 or 3′) from a translation initiation codon. Similarly, the terms “stop codon region” and “translation termination codon region” refer to a portion of such an mRNA or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction (i.e., 5′ or 3′) from a translation termination codon.

The open reading frame (ORF) or “coding region,” which is known in the art to refer to the region between the translation initiation codon and the translation termination codon, is also a region which may be targeted effectively. Other target regions include the 5′ untranslated region (5′UTR), known in the art to refer to the portion of an mRNA in the 5′ direction from the translation initiation codon, and thus including nucleotides between the 5′ cap site and the translation initiation codon of an mRNA or corresponding nucleotides on the gene, and the 3′ untranslated region (3′UTR), known in the art to refer to the portion of an mRNA in the 3′ direction from the translation termination codon, and thus including nucleotides between the translation termination codon and 3′ end of an mRNA or corresponding nucleotides on the gene. The 5′ cap of an mRNA comprises an N7-methylated guanosine residue joined to the 5′-most residue of the mRNA via a 5′-5′ triphosphate linkage. The 5′ cap region of an mRNA is considered to include the 5′ cap structure itself as well as the first 50 nucleotides adjacent to the cap. The 5′ cap region may also be a preferred target region.

Although some eukaryotic mRNA transcripts are directly translated, many contain one or more regions, known as “introns,” which are excised from a transcript before it is translated. The remaining (and therefore translated) regions are known as “exons” and are spliced together to form a continuous mRNA sequence. mRNA splice sites, i.e., intron-exon junctions, may also be preferred target regions, and are particularly useful in situations where aberrant splicing is implicated in disease, or where an overproduction of a particular mRNA splice product is implicated in disease. Aberrant fusion junctions due to rearrangements or deletions are also preferred targets. mRNA transcripts produced via the process of splicing of two (or more) mRNAs from different gene sources are known as “fusion transcripts. It has also been found that introns can also be effective, and therefore preferred, target regions for antisense compounds targeted, for example, to DNA or pre-mRNA.

It is also known in the art that alternative RNA transcripts can be produced from the same genomic region of DNA. These alternative transcripts are generally known as “variants”. More specifically, “pre-mRNA variants” are transcripts produced from the same genomic DNA that differ from other transcripts produced from the same genomic DNA in either their start or stop position and contain both intronic and extronic regions.

Upon excision of one or more exon or intron regions or portions thereof during splicing, pre-mRNA variants produce smaller “mRNA variants”. Consequently, mRNA variants are processed pre-mRNA variants and each unique pre-mRNA variant must always produce a unique mRNA variant as a result of splicing. These mRNA variants are also known as “alternative splice variants”. If no splicing of the pre-mRNA variant occurs then the pre-mRNA variant is identical to the MRNA variant.

It is also known in the art that variants can be produced through the use of alternative signals to start or stop transcription and that pre-mRNAs and mRNAs can possess more that one start codon or stop codon. Variants that originate from a pre-mRNA or mRNA that use alternative start codons are known as “alternative start variants” of that pre-mRNA or mRNA. Those transcripts that use an alternative stop codon are known as “alternative stop variants” of that pre-mRNA or mRNA. One specific type of alternative stop variant is the “polyA variant” in which the multiple transcripts produced result from the alternative selection of one of the “polyA stop signals” by the transcription machinery, thereby producing transcripts that terminate at unique polyA sites.

Once one or more target sites have been identified, oligonucleotides are chosen which are sufficiently complementary to the target, i.e., hybridize sufficiently well and with sufficient specificity, to give the desired effect.

In the context of this invention, “hybridization” means hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleoside or nucleotide bases. For example, adenine and thymine are complementary nucleobases which pair through the formation of hydrogen bonds. “Complementary,” as used herein, refers to the capacity for precise pairing between two nucleotides. For example, if a nucleotide at a certain position of an oligonucleotide is capable of hydrogen bonding with a nucleotide at the same position of a DNA or RNA molecule, then the oligonucleotide and the DNA or RNA are considered to be complementary to each other at that position. The oligonucleotide and the DNA or RNA are complementary to each other when a sufficient number of corresponding positions in each molecule are occupied by nucleotides which can hydrogen bond with each other. Thus, “specifically hybridizable” and “complementary” are terms which are used to indicate a sufficient degree of complementarity or precise pairing such that stable and specific binding occurs between the oligonucleotide and the DNA or RNA target. It is understood in the art that the sequence of an antisense compound need not be 100% complementary to that of its target nucleic acid to be specifically hybridizable. An antisense compound is specifically hybridizable when binding of the compound to the target DNA or RNA molecule interferes with the normal function of the target DNA or RNA to cause a loss of utility, and there is a sufficient degree of complementarity to avoid non-specific binding of the antisense compound to non-target sequences under conditions in which specific binding is desired, i.e., under physiological conditions in the case of in vivo assays or therapeutic treatment, and in the case of in vitro assays, under conditions in which the assays are performed.

Antisense and other compounds of the invention which hybridize to the target and inhibit expression of the target are identified through experimentation, and the sequences of these compounds are hereinbelow identified as preferred embodiments of the invention. The target sites to which these preferred sequences are complementary are hereinbelow referred to as “active sites” and are therefore preferred sites for targeting. Therefore another embodiment of the invention encompasses compounds which hybridize to these active sites.

Antisense compounds are commonly used as research reagents and diagnostics. For example, antisense oligonucleotides, which are able to inhibit gene expression with exquisite specificity, are often used by those of ordinary skill to elucidate the function of particular genes. Antisense compounds are also used, for example, to distinguish between functions of various members of a biological pathway. Antisense modulation has, therefore, been harnessed for research use.

For use in kits and diagnostics, the antisense compounds of the present invention, either alone or in combination with other antisense compounds or therapeutics, can be used as tools in differential and/or combinatorial analyses to elucidate expression patterns of a portion or the entire complement of genes expressed within cells and tissues.

Expression patterns within cells or tissues treated with one or more antisense compounds are compared to control cells or tissues not treated with antisense compounds and the patterns produced are analyzed for differential levels of gene expression as they pertain, for example, to disease association, signaling pathway, cellular localization, expression level, size, structure or function of the genes examined. These analyses can be performed on stimulated or unstimulated cells and in the presence or absence of other compounds which affect expression patterns.

Examples of methods of gene expression analysis known in the art include DNA arrays or microarrays (Brazma and Vilo, FEBS Lett., 2000, 480, 17-24; Celis, et al., FEBS Lett., 2000, 480, 2-16), SAGE (serial analysis of gene expression)(Madden, et al., Drug Discov. Today, 2000, 5, 415-425), READS (restriction enzyme amplification of digested cDNAs) (Prashar and Weissman, Methods Enzymol., 1999, 303, 258-72), TOGA (total gene expression analysis) (Sutcliffe, et al., Proc. Natl. Acad. Sci. U.S.A., 2000, 97, 1976-81), protein arrays and proteomics (Celis, et al., FEBS Lett., 2000, 480, 2-16; Jungblut, et al., Electrophoresis, 1999, 20, 2100-10), expressed sequence tag (EST) sequencing (Celis, et al., FEBS Lett., 2000, 480, 2-16; Larsson, et al., J. Biotechnol., 2000, 80, 143-57), subtractive RNA fingerprinting (SuRF) (Fuchs, et al., Anal. Biochem., 2000, 286, 91-98; Larson, et al., Cytometry, 2000, 41, 203-208), subtractive cloning, differential display (DD) (Jurecic and Belmont, Curr. Opin. Microbiol., 2000, 3, 316-21), comparative genomic hybridization (Carulli, et al., J. Cell Biochem. Suppl., 1998, 31, 286-96), FISH (fluorescent in situ hybridization) techniques (Going and Gusterson, Eur. J. Cancer, 1999, 35, 1895-904) and mass spectrometry methods (reviewed in (To, Comb. Chem. High Throughput Screen, 2000, 3, 235-41).

The specificity and sensitivity of antisense is also harnessed by those of skill in the art for therapeutic uses. Antisense oligonucleotides have been employed as therapeutic moieties in the treatment of disease states in animals and man. Antisense oligonucleotide drugs, including ribozymes, have been safely and effectively administered to humans and numerous clinical trials are presently underway. It is thus established that oligonucleotides can be useful therapeutic modalities that can be configured to be useful in treatment regimes for treatment of cells, tissues and animals, especially humans.

In the context of this invention, the term “oligonucleotide” refers to an oligomer or polymer of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) or mimetics thereof. This term includes oligonucleotides composed of naturally-occurring nucleobases, sugars and covalent internucleoside (backbone) linkages as well as oligonucleotides having non-naturally-occurring portions which function similarly. Such modified or substituted oligonucleotides are often preferred over native forms because of desirable properties such as, for example, enhanced cellular uptake, enhanced affinity for nucleic acid target and increased stability in the presence of nucleases.

While antisense oligonucleotides are a preferred form of antisense compound, the present invention comprehends other oligomeric antisense compounds, including but not limited to oligonucleotide mimetics such as are described below. The antisense compounds in accordance with this invention preferably comprise from about 8 to about 50 nucleobases (i.e. from about 8 to about 50 linked nucleosides). Particularly preferred antisense compounds are antisense oligonucleotides, even more preferably those comprising from about 12 to about 30 nucleobases. Antisense compounds include ribozymes, external guide sequence (EGS) oligonucleotides (oligozymes), and other short catalytic RNAs or catalytic oligonucleotides which hybridize to the target nucleic acid and modulate its expression.

As is known in the art, a nucleoside is a base-sugar combination. The base portion of the nucleoside is normally a heterocyclic base. The two most common classes of such heterocyclic bases are the purines and the pyrimidines. Nucleotides are nucleosides that further include a phosphate group covalently linked to the sugar portion of the nucleoside. For those nucleosides that include a pentofuranosyl sugar, the phosphate group can be linked to either the 2′, 3′ or 5′ hydroxyl moiety of the sugar. In forming oligonucleotides, the phosphate groups covalently link adjacent nucleosides to one another to form a linear polymeric compound. In turn the respective ends of this linear polymeric structure can be further joined to form a circular structure, however, open linear structures are generally preferred. Within the oligonucleotide structure, the phosphate groups are commonly referred to as forming the internucleoside backbone of the oligonucleotide. The normal linkage or backbone of RNA and DNA is a 3′ to 5′ phosphodiester linkage.

Specific examples of preferred antisense compounds useful in this invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages. As defined in this specification, oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in the backbone. For the purposes of this specification, and as sometimes referenced in the art, modified oligonucleotides that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides.

Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotri-esters, methyl and other alkyl phosphonates including 3′-alkylene phosphonates, 5′-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3′-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, selenophosphates and borano-phosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those having inverted polarity wherein one or more internucleotide linkages is a 3′ to 3′, 5′ to 5′ or 2′ to 2′ linkage. Preferred oligonucleotides having inverted polarity comprise a single 3′ to 3′ linkage at the 3′-most internucleotide linkage i.e. a single inverted nucleoside residue which may be abasic (the nucleobase is missing or has a hydroxyl group in place thereof). Various salts, mixed salts and free acid forms are also included.

Representative United States patents that teach the preparation of the above phosphorus-containing linkages include, but are not limited to, U.S. Pat. Nos. 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; 5,194,599; 5,565,555; 5,527,899; 5,721,218; 5,672,697 and 5,625,050, certain of which are commonly owned with this application, and each of which is herein incorporated by reference.

Preferred modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; riboacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH ₂component parts.

Representative United States patents that teach the preparation of the above oligonucleosides include, but are not limited to, U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; 5,792,608; 5,646,269 and 5,677,439, certain of which are commonly owned with this application, and each of which is herein incorporated by reference.

In other preferred oligonucleotide mimetics, both the sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. One such oligomeric compound, an oligonucleotide mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar-backbone of an oligonucleotide is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone. Representative United States patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found in Nielsen et al., Science, 1991, 254, 1497-1500.

Most preferred embodiments of the invention are oligonucleotides with phosphorothioate backbones and oligonucleosides with heteroatom backbones, and in particular —CH ₂—NH—O—CH₂—, —CH₂—N(CH₃)—O—CH₂— [known as a methylene (methylimino) or MMI backbone], —CH₂—O—N(CH₃)—CH₂—, —CH₂—N(CH₃)—N(CH₃)—CH₂— and —O—N(CH₂)—CH₂—CH₂— [wherein the native phosphodiester backbone is represented as —O—P—O—CH₂—] of the above referenced U.S. Pat. No. 5,489,677, and the amide backbones of the above referenced U.S. Pat. No. 5,602,240. Also preferred are oligonucleotides having morpholino backbone structures of the above-referenced U.S. Pat. No. 5,034,506.

Modified oligonucleotides may also contain one or more substituted sugar moieties. Preferred oligonucleotides comprise one of the following at the 2′ position: OH; F; O—, S—, or N-alkyl; O—, S—, or N-alkenyl; O—, S— or N— alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C ₁to C₁₀alkyl or C₂to C₁₀alkenyl and alkynyl. Particularly preferred are O[(CH₂)_nO]_mCH₃, O(CH₂)_nOCH₃, O(CH₂)_nNH₂, O(CH₂)_nCH₃, O(CH₂)_nONH₂, and O(CH₂)_nON[(CH₂)_nCH₃)]₂, where n and m are from 1 to about 10. Other preferred oligonucleotides comprise one of the following at the 2′ position: C₁to C₁₀lower alkyl, substituted lower alkyl, alkenyl, alkynyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH₃, OCN, Cl, Br, CN, CF₃, OCF₃, SOCH₃, SO₂CH₃, ONO₂, NO₂, N₃, NH₂, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide, and other substituents having similar properties. A preferred modification includes 2′-methoxyethoxy (2′-O-CH₂CH₂OCH₃, also known as 2′-O-(2-methoxyethyl) or 2′-MOE) (Martin et al., Helv. Chim. Acta, 1995, 78, 486-504) i.e., an alkoxyalkoxy group. A further preferred modification includes 2′-dimethylaminooxyethoxy, i.e., a O(CH₂)₂ON(CH₃)₂group, also known as 2′-DMAOE, as described in examples hereinbelow, and 2′-dimethylaminoethoxyethoxy (also known in the art as 2′-O-dimethylaminoethoxyethyl or 2′-DMAEOE), i.e., 2′—O—CH₂—O—CH₂—N(CH₂)₂, also described in examples hereinbelow.

A further preferred modification includes Locked Nucleic Acids (LNAs) in which the 2′-hydroxyl group is linked to the 3′ or 4′ carbon atom of the sugar ring thereby forming a bicyclic sugar moiety. The linkage is preferably a methelyne (—CH ₂—)_ngroup bridging the 2′ oxygen atom and the 4′ carbon atom wherein n is 1 or 2. LNAs and preparation thereof are described in WO 98/39352 and WO 99/14226.

Other preferred modifications include 2′-methoxy (2′—O—CH ₃), 2′-aminopropoxy (2′-OCH₂CH₂CH₂NH₂), 2′-allyl (2′-CH₂-CH=CH₂), 2′-O-allyl (2′—O—CH₂—CH═CH₂) and 2′-fluoro (2′-F). The 2′-modification may be in the arabino (up) position or ribo (down) position. A preferred 2′-arabino modification is 2′-F. Similar modifications may also be made at other positions on the oligonucleotide, particularly the 3′ position of the sugar on the 3′ terminal nucleotide or in 2′-5′ linked oligonucleotides and the 5′ position of 5′ terminal nucleotide. Oligonucleotides may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar. Representative United States patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S. Pat. Nos. 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; 5,792,747; and 5,700,920, certain of which are commonly owned with the instant application, and each of which is herein incorporated by reference in its entirety.

Oligonucleotides may also include nucleobase (often referred to in the art simply as “base”) modifications or substitutions. As used herein, “unmodified” or “natural” nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl (—C≡C—CH ₃) uracil and cytosine and other alkynyl derivatives of pyrimidine bases, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 2-F-adenine, 2-amino-adenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine. Further modified nucleobases include tricyclic pyrimidines such as phenoxazine cytidine(1H-pyrimido[5,4-b][1,4]benzoxazin-2(3H)-one), phenothiazine cytidine (lH-pyrimido[5,4-b][1,4]benzothiazin-2(3H)-one), G-clamps such as a substituted phenoxazine cytidine (e.g. 9-(2-aminoethoxy)-H-pyrimido[5,4-b][1,4]benzoxazin-2(3H)-one), carbazole cytidine (2H-pyrimido[4,5-b]indol-2-one), pyridoindole cytidine (H-pyrido[3′,2′:4,5]pyrrolo[2,3-d]pyrimidin-2-one). Modified nucleobases may also include those in which the purine or pyrimidine base is replaced with other heterocycles, for example 7-deaza-adenine, 7-deazaguanosine, 2-aminopyridine and 2-pyridone. Further nucleobases include those disclosed in U.S. Pat. No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, pages 858-859, Kroschwitz, J. I., ed. John Wiley & Sons, 1990, those disclosed by Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613, and those disclosed by Sanghvi, Y.S., Chapter 15, Antisense Research and Applications, pages 289-302, Crooke, S. T. and Lebleu, B. ed., CRC Press, 1993. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds of the invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2° C. (Sanghvi, Y. S., Crooke, S. T. and Lebleu, B., eds., Antisense Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are presently preferred base substitutions, even more particularly when combined with 2′-O-methoxyethyl sugar modifications.

Representative United States patents that teach the preparation of certain of the above noted modified nucleobases as well as other modified nucleobases include, but are not limited to, the above noted U.S. Pat. No. 3,687,808, as well as U.S. Pat. Nos. 4,845,205; 5,130,302; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,121, 5,596,091; 5,614,617; 5,645,985; 5,830,653; 5,763,588; 6,005,096; and 5,681,941, certain of which are commonly owned with the instant application, and each of which is herein incorporated by reference, and U.S. Pat. No. 5,750,692, which is commonly owned with the instant application and also herein incorporated by reference.

Another modification of the oligonucleotides of the invention involves chemically linking to the oligonucleotide one or more moieties or conjugates which enhance the activity, cellular distribution or cellular uptake of the oligonucleotide. The compounds of the invention can include conjugate groups covalently bound to functional groups such as primary or secondary hydroxyl groups. Conjugate groups of the invention include intercalators, reporter molecules, polyamines, polyamides, polyethylene glycols, polyethers, groups that enhance the pharmacodynamic properties of oligomers, and groups that enhance the pharmacokinetic properties of oligomers. Typical conjugates groups include cholesterols, lipids, phospholipids, biotin, phenazine, folate, phenanthridine, anthraquinone, acridine, fluoresceins, rhodamines, coumarins, and dyes. Groups that enhance the pharmacodynamic properties, in the context of this invention, include groups that improve oligomer uptake, enhance oligomer resistance to degradation, and/or strengthen sequence-specific hybridization with RNA. Groups that enhance the pharmacokinetic properties, in the context of this invention, include groups that improve oligomer uptake, distribution, metabolism or excretion. Representative conjugate groups are disclosed in International Patent Application PCT/US92/09196, filed Oct. 23, 1992 the entire disclosure of which is incorporated herein by reference. Conjugate moieties include but are not limited to lipid moieties such as a cholesterol moiety (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 6553-6556), cholic acid (Manoharan et al., Bioorg. Med. Chem. Let., 1994, 4, 1053-1060), a thioether, e.g., hexyl-S-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Bioorg. Med. Chem. Let., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20, 533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al., EMBO J., 1991, 10, 1111-1118; Kabanov et al., FEBS Lett., 1990, 259, 327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethyl-ammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937. Oligonucleotides of the invention may also be conjugated to active drug substances, for example, aspirin, warfarin, phenylbutazone, ibuprofen, suprofen, fenbufen, ketoprofen, (S)-(+)-pranoprofen, carprofen, dansylsarcosine, 2,3,5-triiodobenzoic acid, flufenamic acid, folinic acid, a benzothiadiazide, chlorothiazide, a diazepine, indomethicin, a barbiturate, a cephalosporin, a sulfa drug, an antidiabetic, an antibacterial or an antibiotic. Oligonucleotide-drug conjugates and their preparation are described in U.S. patent application Ser. No. 09/334,130 (filed Jun. 15, 1999) which is incorporated herein by reference in its entirety.

Representative United States patents that teach the preparation of such oligonucleotide conjugates include, but are not limited to, U.S. Pat. Nos. 4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717, 5,580,731; 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045; 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263; 4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136; 5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723; 5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696; 5,599,923; 5,599,928 and 5,688,941, certain of which are commonly owned with the instant application, and each of which is herein incorporated by reference.

It is not necessary for all positions in a given compound to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an oligonucleotide. The present invention also includes antisense compounds which are chimeric compounds. “Chimeric” antisense compounds or “chimeras,” in the context of this invention, are antisense compounds, particularly oligonucleotides, which contain two or more chemically distinct regions, each made up of at least one monomer unit, i.e., a nucleotide in the case of an oligonucleotide compound. These oligonucleotides typically contain at least one region wherein the oligonucleotide is modified so as to confer upon the oligonucleotide increased resistance to nuclease degradation, increased cellular uptake, and/or increased binding affinity for the target nucleic acid. An additional region of the oligonucleotide may serve as a substrate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. By way of example, RNase H is a cellular endonuclease which cleaves the RNA strand of an RNA:DNA duplex. Activation of RNase H, therefore, results in cleavage of the RNA target, thereby greatly enhancing the efficiency of oligonucleotide inhibition of gene expression. Consequently, comparable results can often be obtained with shorter oligonucleotides when chimeric oligonucleotides are used, compared to phosphorothioate deoxyoligonucleotides hybridizing to the same target region. Cleavage of the RNA target can be routinely detected by gel electrophoresis and, if necessary, associated nucleic acid hybridization techniques known in the art.

Chimeric antisense compounds of the invention may be formed as composite structures of two or more oligonucleotides, modified oligonucleotides, oligonucleosides and/or oligonucleotide mimetics as described above. Such compounds have also been referred to in the art as hybrids or gapmers. Representative United States patents that teach the preparation of such hybrid structures include, but are not limited to, U.S. Pat. Nos. 5,013,830; 5,149,797; 5,220,007; 5,256,775; 5,366,878; 5,403,711; 5,491,133; 5,565,350; 5,623,065; 5,652,355; 5,652,356; and 5,700,922, certain of which are commonly owned with the instant application, and each of which is herein incorporated by reference in its entirety.

The antisense compounds used in accordance with this invention may be conveniently and routinely made through the well-known technique of solid phase synthesis. Equipment for such synthesis is sold by several vendors including, for example, Applied Biosystems (Foster City, Calif.). Any other means for such synthesis known in the art may additionally or alternatively be employed. It is well known to use similar techniques to prepare oligonucleotides such as the phosphorothioates and alkylated derivatives.

The antisense compounds of the invention are synthesized in vitro and do not include antisense compositions of biological origin, or genetic vector constructs designed to direct the in vivo synthesis of antisense molecules.

The compounds of the invention may also be admixed, encapsulated, conjugated or otherwise associated with other molecules, molecule structures or mixtures of compounds, as for example, liposomes, receptor targeted molecules, oral, rectal, topical or other formulations, for assisting in uptake, distribution and/or absorption. Representative United States patents that teach the preparation of such uptake, distribution and/or absorption assisting formulations include, but are not limited to, U.S. Pat. Nos. 5,108,921; 5,354,844; 5,416,016; 5,459,127; 5,521,291; 5,543,158; 5,547,932; 5,583,020; 5,591,721; 4,426,330; 4,534,899; 5,013,556; 5,108,921; 5,213,804; 5,227,170; 5,264,221; 5,356,633; 5,395,619; 5,416,016; 5,417,978; 5,462,854; 5,469,854; 5,512,295; 5,527,528; 5,534,259; 5,543,152; 5,556,948; 5,580,575; and 5,595,756, each of which is herein incorporated by reference.

The antisense compounds of the invention encompass any pharmaceutically acceptable salts, esters, or salts of such esters, or any other compound which, upon administration to an animal including a human, is capable of providing (directly or indirectly) the biologically active metabolite or residue thereof. Accordingly, for example, the disclosure is also drawn to prodrugs and pharmaceutically acceptable salts of the compounds of the invention, pharmaceutically acceptable salts of such prodrugs, and other bioequivalents.

The term “prodrug” indicates a therapeutic agent that is prepared in an inactive form that is converted to an active form (i.e., drug) within the body or cells thereof by the action of endogenous enzymes or other chemicals and/or conditions. In particular, prodrug versions of the oligonucleotides of the invention are prepared as SATE [(S-acetyl-2-thioethyl) phosphate] derivatives according to the methods disclosed in WO 93/24510 to Gosselin et al., published Dec. 9, 1993 or in WO 94/26764 and U.S. Pat. No. 5,770,713 to Imbach et al.

The term “pharmaceutically acceptable salts” refers to physiologically and pharmaceutically acceptable salts of the compounds of the invention: i.e., salts that retain the desired biological activity of the parent compound and do not impart undesired toxicological effects thereto.

Pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Examples of metals used as cations are sodium, potassium, magnesium, calcium, and the like. Examples of suitable amines are N,N′-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, dicyclohexylamine, ethylenediamine, N-methylglucamine, and procaine (see, for example, Berge et al., “pharmaceutical Salts,” J. of Pharma Sci., 1977, 66, 1-19). The base addition salts of said acidic compounds are prepared by contacting the free acid form with a sufficient amount of the desired base to produce the salt in the conventional manner. The free acid form may be regenerated by contacting the salt form with an acid and isolating the free acid in the conventional manner. The free acid forms differ from their respective salt forms somewhat in certain physical properties such as solubility in polar solvents, but otherwise the salts are equivalent to their respective free acid for purposes of the present invention. As used herein, a “pharmaceutical addition salt” includes a pharmaceutically acceptable salt of an acid form of one of the components of the compositions of the invention. These include organic or inorganic acid salts of the amines. Preferred acid salts are the hydrochlorides, acetates, salicylates, nitrates and phosphates. Other suitable pharmaceutically acceptable salts are well known to those skilled in the art and include basic salts of a variety of inorganic and organic acids, such as, for example, with inorganic acids, such as for example hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid; with organic carboxylic, sulfonic, sulfo or phospho acids or N-substituted sulfamic acids, for example acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, fumaric acid, malic acid, tartaric acid, lactic acid, oxalic acid, gluconic acid, glucaric acid, glucuronic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, salicylic acid, 4-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinic acid or isonicotinic acid; and with amino acids, such as the 20 alpha-amino acids involved in the synthesis of proteins in nature, for example glutamic acid or aspartic acid, and also with phenylacetic acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, ethane-1,2-disulfonic acid, benzenesulfonic acid, 4-methylbenzenesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid, 2- or 3-phosphoglycerate, glucose-6-phosphate, N-cyclohexylsulfamic acid (with the formation of cyclamates), or with other acid organic compounds, such as ascorbic acid. Pharmaceutically acceptable salts of compounds may also be prepared with a pharmaceutically acceptable cation. Suitable pharmaceutically acceptable cations are well known to those skilled in the art and include alkaline, alkaline earth, ammonium and quaternary ammonium cations: Carbonates or hydrogen carbonates are also possible.

For oligonucleotides, preferred examples of pharmaceutically acceptable salts include but are not limited to (a) salts formed with cations such as sodium, potassium, ammonium, magnesium, calcium, polyamines such as spermine and spermidine, etc.; (b) acid addition salts formed with inorganic acids, for example hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and the like; (c) salts formed with organic acids such as, for example, acetic acid, oxalic acid, tartaric acid, succinic acid, maleic acid, fumaric acid, gluconic acid, citric acid, malic acid, ascorbic acid, benzoic acid, tannic acid, palmitic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acid, polygalacturonic acid, and the like; and (d) salts formed from elemental anions such as chlorine, bromine, and iodine.

The antisense compounds of the present invention can be utilized for diagnostics, therapeutics, prophylaxis and as research reagents and kits. For therapeutics, an animal, preferably a human, suspected of having a disease or disorder which can be treated by modulating the expression of estrogen receptor alpha is treated by administering antisense compounds in accordance with this invention. The compounds of the invention can be utilized in pharmaceutical compositions by adding an effective amount of an antisense compound to a suitable pharmaceutically acceptable diluent or carrier. Use of the antisense compounds and methods of the invention may also be useful prophylactically, e.g., to prevent or delay infection, inflammation or tumor formation, for example.

The antisense compounds of the invention are useful for research and diagnostics, because these compounds hybridize to nucleic acids encoding estrogen receptor alpha, enabling sandwich and other assays to easily be constructed to exploit this fact. Hybridization of the antisense oligonucleotides of the invention with a nucleic acid encoding estrogen receptor alpha can be detected by means known in the art. Such means may include conjugation of an enzyme to the oligonucleotide, radiolabelling of the oligonucleotide or any other suitable detection means. Kits using such detection means for detecting the level of estrogen receptor alpha in a sample may also be prepared.

The present invention also includes pharmaceutical compositions and formulations which include the antisense compounds of the invention. The pharmaceutical compositions of the present invention may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration may be topical (including ophthalmic and to mucous membranes including vaginal and rectal delivery), pulmonary, e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. Oligonucleotides with at least one 2′-O-methoxyethyl modification are believed to be particularly useful for oral administration.

Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Coated condoms, gloves and the like may also be useful. Preferred topical formulations include those in which the oligonucleotides of the invention are in admixture with a topical delivery agent such as lipids, liposomes, fatty acids, fatty acid esters, steroids, chelating agents and surfactants. Preferred lipids and liposomes include neutral (e.g. dioleoylphosphatidyl DOPE ethanolamine, dimyristoylphosphatidyl choline DMPC, distearolyphosphatidyl choline) negative (e.g. dimyristoylphosphatidyl glycerol DMPG) and cationic (e.g. dioleoyltetramethylaminopropyl DOTAP and dioleoylphosphatidyl ethanolamine DOTMA). Oligonucleotides of the invention may be encapsulated within liposomes or may form complexes thereto, in particular to cationic liposomes. Alternatively, oligonucleotides may be complexed to lipids, in particular to cationic lipids. Preferred fatty acids and esters include but are not limited arachidonic acid, oleic acid, eicosanoic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a C _1-10alkyl ester (e.g. isopropylmyristate IPM), monoglyceride, diglyceride or pharmaceutically acceptable salt thereof. Topical formulations are described in detail in U.S. patent application Ser. No. 09/315,298 filed on May 20, 1999 which is incorporated herein by reference in its entirety.

Compositions and formulations for oral administration include powders or granules, microparticulates, nanoparticulates, suspensions or solutions in water or non-aqueous media, capsules, gel capsules, sachets, tablets or minitablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing aids or binders may be desirable. Preferred oral formulations are those in which oligonucleotides of the invention are administered in conjunction with one or more penetration enhancers surfactants and chelators. Preferred surfactants include fatty acids and/or esters or salts thereof, bile acids and/or salts thereof. Preferred bile acids/salts include chenodeoxycholic acid (CDCA) and ursodeoxychenodeoxycholic acid (UDCA), cholic acid, dehydrocholic acid, deoxycholic acid, glucholic acid, glycholic acid, glycodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, sodium tauro-24,25-dihydro-fusidate, sodium glycodihydrofusidate. Prefered fatty acids include arachidonic acid, undecanoic acid, oleic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a monoglyceride, a diglyceride or a pharmaceutically acceptable salt thereof (e.g. sodium). Also prefered are combinations of penetration enhancers, for example, fatty acids/salts in combination with bile acids/salts. A particularly preferred combination is the sodium salt of lauric acid, capric acid and UDCA. Further penetration enhancers include polyoxyethylene-9-lauryl ether, polyoxyethylene-20-cetyl ether. Oligonucleotides of the invention may be delivered orally in granular form including sprayed dried particles, or complexed to form micro or nanoparticles. Oligonucleotide complexing agents include poly-amino acids; polyimines; polyacrylates; polyalkylacrylates, polyoxethanes, polyalkylcyanoacrylates; cationized gelatins, albumins, starches, acrylates, polyethyleneglycols (PEG) and starches; polyalkylcyanoacrylates; DEAE-derivatized polyimines, pollulans, celluloses and starches. Particularly preferred complexing agents include chitosan, N-trimethylchitosan, poly-L-lysine, polyhistidine, polyornithine, polyspermines, protamine, polyvinylpyridine, polythiodiethylamino-methylethylene P(TDAE), polyaminostyrene (e.g. p-amino), poly(methylcyanoacrylate), poly(ethylcyanoacrylate), poly(butylcyanoacrylate), poly(isobutylcyanoacrylate), poly(isohexylcynaoacrylate), DEAE-methacrylate, DEAE-hexylacrylate, DEAE-acrylamide, DEAE-albumin and DEAE-dextran, polymethylacrylate, polyhexylacrylate, poly(D,L-lactic acid), poly(DL-lactic-co-glycolic acid (PLGA), alginate, and polyethyleneglycol (PEG). Oral formulations for oligonucleotides and their preparation are described in detail in U.S. application Ser. No. 08/886,829 (filed Jul. 1, 1997), Ser. No. 09/108,673 (filed Jul. 1, 1998), Ser. No. 09/256,515 (filed Feb. 23, 1999), Ser. No. 09/082,624 (filed May 21, 1998) and Ser. No. 09/315,298 (filed May 20, 1999) each of which is incorporated herein by reference in their entirety.

Compositions and formulations for parenteral, intrathecal or intraventricular administration may include sterile aqueous solutions which may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients.

Pharmaceutical compositions of the present invention include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated from a variety of components that include, but are not limited to, preformed liquids, self-emulsifying solids and self-emulsifying semisolids.

The pharmaceutical formulations of the present invention, which may conveniently be presented in unit dosage form, may be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product.

The compositions of the present invention may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, gel capsules, liquid syrups, soft gels, suppositories, and enemas. The compositions of the present invention may also be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions may further contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers.

In one embodiment of the present invention the pharmaceutical compositions may be formulated and used as foams. Pharmaceutical foams include formulations such as, but not limited to, emulsions, microemulsions, creams, jellies and liposomes. While basically similar in nature these formulations vary in the components and the consistency of the final product. The preparation of such compositions and formulations is generally known to those skilled in the pharmaceutical and formulation arts and may be applied to the formulation of the compositions of the present invention.

Emulsions

The compositions of the present invention may be prepared and formulated as emulsions. Emulsions are typically heterogenous systems of one liquid dispersed in another in the form of droplets usually exceeding 0.1 μm in diameter. (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199; Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., Volume 1, p. 245; Block in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 2, p. 335; Higuchi et al., in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 301). Emulsions are often biphasic systems comprising of two immiscible liquid phases intimately mixed and dispersed with each other. In general, emulsions may be either water-in-oil (w/o) or of the oil-in-water (o/w) variety. When an aqueous phase is finely divided into and dispersed as minute droplets into a bulk oily phase the resulting composition is called a water-in-oil (w/o) emulsion. Alternatively, when an oily phase is finely divided into and dispersed as minute droplets into a bulk aqueous phase the resulting composition is called an oil-in-water (o/w) emulsion. Emulsions may contain additional components in addition to the dispersed phases and the active drug which may be present as a solution in either the aqueous phase, oily phase or itself as a separate phase. Pharmaceutical excipients such as emulsifiers, stabilizers, dyes, and anti-oxidants may also be present in emulsions as needed. Pharmaceutical emulsions may also be multiple emulsions that are comprised of more than two phases such as, for example, in the case of oil-in-water-in-oil (o/w/o) and water-in-oil-in-water (w/o/w) emulsions. Such complex formulations often provide certain advantages that simple binary emulsions do not. Multiple emulsions in which individual oil droplets of an o/w emulsion enclose small water droplets constitute a w/o/w emulsion. Likewise a system of oil droplets enclosed in globules of water stabilized in an oily continuous provides an o/w/o emulsion.

Emulsions are characterized by little or no thermodynamic stability. Often, the dispersed or discontinuous phase of the emulsion is well dispersed into the external or continuous phase and maintained in this form through the means of emulsifiers or the viscosity of the formulation. Either of the phases of the emulsion may be a semisolid or a solid, as is the case of emulsion-style ointment bases and creams. Other means of stabilizing emulsions entail the use of emulsifiers that may be incorporated into either phase of the emulsion. Emulsifiers may broadly be classified into four categories: synthetic surfactants, naturally occurring emulsifiers, absorption bases, and finely dispersed solids (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).

Synthetic surfactants, also known as surface active agents, have found wide applicability in the formulation of emulsions and have been reviewed in the literature (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), Marcel Dekker, Inc., New York, N.Y., 1988, volume 1, p. 199). Surfactants are typically amphiphilic and comprise a hydrophilic and a hydrophobic portion. The ratio of the hydrophilic to the hydrophobic nature of the surfactant has been termed the hydrophile/lipophile balance (HLB) and is a valuable tool in categorizing and selecting surfactants in the preparation of formulations. Surfactants may be classified into different classes based on the nature of the hydrophilic group: nonionic, anionic, cationic and amphoteric (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285).

Naturally occurring emulsifiers used in emulsion formulations include lanolin, beeswax, phosphatides, lecithin and acacia. Absorption bases possess hydrophilic properties such that they can soak up water to form w/o emulsions yet retain their semisolid consistencies, such as anhydrous lanolin and hydrophilic petrolatum. Finely divided solids have also been used as good emulsifiers especially in combination with surfactants and in viscous preparations. These include polar inorganic solids, such as heavy metal hydroxides, nonswelling clays such as bentonite, attapulgite, hectorite, kaolin, montmorillonite, colloidal aluminum silicate and colloidal magnesium aluminum silicate, pigments and nonpolar solids such as carbon or glyceryl tristearate.

A large variety of non-emulsifying materials are also included in emulsion formulations and contribute to the properties of emulsions. These include fats, oils, waxes, fatty acids, fatty alcohols, fatty esters, humectants, hydrophilic colloids, preservatives and antioxidants (Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).

Hydrophilic colloids or hydrocolloids include naturally occurring gums and synthetic polymers such as polysaccharides (for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth), cellulose derivatives (for example, carboxymethylcellulose and carboxypropylcellulose), and synthetic polymers (for example, carbomers, cellulose ethers, and carboxyvinyl polymers). These disperse or swell in water to form colloidal solutions that stabilize emulsions by forming strong interfacial films around the dispersed-phase droplets and by increasing the viscosity of the external phase.

Since emulsions often contain a number of ingredients such as carbohydrates, proteins, sterols and phosphatides that may readily support the growth of microbes, these formulations often incorporate preservatives. Commonly used preservatives included in emulsion formulations include methyl paraben, propyl paraben, quaternary ammonium salts, benzalkonium chloride, esters of p-hydroxybenzoic acid, and boric acid. Antioxidants are also commonly added to emulsion formulations to prevent deterioration of the formulation. Antioxidants used may be free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabisulfite, and antioxidant synergists such as citric acid, tartaric acid, and lecithin.

The application of emulsion formulations via dermatological, oral and parenteral routes and methods for their manufacture have been reviewed in the literature (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Emulsion formulations for oral delivery have been very widely used because of reasons of ease of formulation, efficacy from an absorption and bioavailability standpoint. (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Mineral-oil base laxatives, oil-soluble vitamins and high fat nutritive preparations are among the materials that have commonly been administered orally as o/w emulsions.

In one embodiment of the present invention, the compositions of oligonucleotides and nucleic acids are formulated as microemulsions. A microemulsion may be defined as a system of water, oil and amphiphile which is a single optically isotropic and thermodynamically stable liquid solution (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Typically microemulsions are systems that are prepared by first dispersing an oil in an aqueous surfactant solution and then adding a sufficient amount of a fourth component, generally an intermediate chain-length alcohol to form a transparent system. Therefore, microemulsions have also been described as thermodynamically stable, isotropically clear dispersions of two immiscible liquids that are stabilized by interfacial films of surface-active molecules (Leung and Shah, in: Controlled Release of Drugs: Polymers and Aggregate Systems, Rosoff, M., Ed., 1989, VCH Publishers, New York, pages 185-215). Microemulsions commonly are prepared via a combination of three to five components that include oil, water, surfactant, cosurfactant and electrolyte. Whether the microemulsion is of the water-in-oil (w/o) or an oil-in-water (o/w) type is dependent on the properties of the oil and surfactant used and on the structure and geometric packing of the polar heads and hydrocarbon tails of the surfactant molecules (Schott, in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 271).

The phenomenological approach utilizing phase diagrams has been extensively studied and has yielded a comprehensive knowledge, to one skilled in the art, of how to formulate microemulsions (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335). Compared to conventional emulsions, microemulsions offer the advantage of solubilizing water-insoluble drugs in a formulation of thermodynamically stable droplets that are formed spontaneously.

Surfactants used in the preparation of microemulsions include, but are not limited to, ionic surfactants, non-ionic surfactants, Brij 96, polyoxyethylene oleyl ethers, polyglycerol fatty acid esters, tetraglycerol monolaurate (ML310), tetraglycerol monooleate (MO310), hexaglycerol monooleate (PO310), hexaglycerol pentaoleate (PO500), decaglycerol monocaprate (MCA750), decaglycerol monooleate (MO750), decaglycerol sequioleate (S0750), decaglycerol decaoleate (DAO750), alone or in combination with cosurfactants. The cosurfactant, usually a short-chain alcohol such as ethanol, 1-propanol, and 1-butanol, serves to increase the interfacial fluidity by penetrating into the surfactant film and consequently creating a disordered film because of the void space generated among surfactant molecules. Microemulsions may, however, be prepared without the use of cosurfactants and alcohol-free self-emulsifying microemulsion systems are known in the art. The aqueous phase may typically be, but is not limited to, water, an aqueous solution of the drug, glycerol, PEG300, PEG400, polyglycerols, propylene glycols, and derivatives of ethylene glycol. The oil phase may include, but is not limited to, materials such as Captex 300, Captex 355, Capmul MCM, fatty acid esters, medium chain (C8-C12) mono, di, and tri-glycerides, polyoxyethylated glyceryl fatty acid esters, fatty alcohols, polyglycolized glycerides, saturated polyglycolized C8-C10 glycerides, vegetable oils and silicone oil.

Microemulsions are particularly of interest from the standpoint of drug solubilization and the enhanced absorption of drugs. Lipid based microemulsions (both o/w and w/o) have been proposed to enhance the oral bioavailability of drugs, including peptides (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385-1390; Ritschel, Meth. Find. Exp. Clin. Pharmacol., 1993, 13, 205). Microemulsions afford advantages of improved drug solubilization, protection of drug from enzymatic hydrolysis, possible enhancement of drug absorption due to surfactant-induced alterations in membrane fluidity and permeability, ease of preparation, ease of oral administration over solid dosage forms, improved clinical potency, and decreased toxicity (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385; Ho et al., J. Pharm. Sci., 1996, 85, 138-143). Often microemulsions may form spontaneously when their components are brought together at ambient temperature. This may be particularly advantageous when formulating thermolabile drugs, peptides or oligonucleotides. Microemulsions have also been effective in the transdermal delivery of active components in both cosmetic and pharmaceutical applications. It is expected that the microemulsion compositions and formulations of the present invention will facilitate the increased systemic absorption of oligonucleotides and nucleic acids from the gastrointestinal tract, as well as improve the local cellular uptake of oligonucleotides and nucleic acids within the gastrointestinal tract, vagina, buccal cavity and other areas of administration.

Microemulsions of the present invention may also contain additional components and additives such as sorbitan monostearate (Grill 3), Labrasol, and penetration enhancers to improve the properties of the formulation and to enhance the absorption of the oligonucleotides and nucleic acids of the present invention. Penetration enhancers used in the microemulsions of the present invention may be classified as belonging to one of five broad categories—surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Each of these classes has been discussed above.

Liposomes

There are many organized surfactant structures besides microemulsions that have been studied and used for the formulation of drugs. These include monolayers, micelles, bilayers and vesicles. Vesicles, such as liposomes, have attracted great interest because of their specificity and the duration of action they offer from the standpoint of drug delivery. As used in the present invention, the term “liposome” means a vesicle composed of amphiphilic lipids arranged in a spherical bilayer or bilayers.

Liposomes are unilamellar or multilamellar vesicles which have a membrane formed from a lipophilic material and an aqueous interior. The aqueous portion contains the composition to be delivered. Cationic liposomes possess the advantage of being able to fuse to the cell wall. Non-cationic liposomes, although not able to fuse as efficiently with the cell wall, are taken up by macrophages in vivo.

In order to cross intact mammalian skin, lipid vesicles must pass through a series of fine pores, each with a diameter less than 50 nm, under the influence of a suitable transdermal gradient. Therefore, it is desirable to use a liposome which is highly deformable and able to pass through such fine pores.

Further advantages of liposomes include; liposomes obtained from natural phospholipids are biocompatible and biodegradable; liposomes can incorporate a wide range of water and lipid soluble drugs; liposomes can protect encapsulated drugs in their internal compartments from metabolism and degradation (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Important considerations in the preparation of liposome formulations are the lipid surface charge, vesicle size and the aqueous volume of the liposomes.

Liposomes are useful for the transfer and delivery of active ingredients to the site of action. Because the liposomal membrane is structurally similar to biological membranes, when liposomes are applied to a tissue, the liposomes start to merge with the cellular membranes. As the merging of the liposome and cell progresses, the liposomal contents are emptied into the cell where the active agent may act.

Liposomal formulations have been the focus of extensive investigation as the mode of delivery for many drugs. There is growing evidence that for topical administration, liposomes present several advantages over other formulations. Such advantages include reduced side-effects related to high systemic absorption of the administered drug, increased accumulation of the administered drug at the desired target, and the ability to administer a wide variety of drugs, both hydrophilic and hydrophobic, into the skin.

Several reports have detailed the ability of liposomes to deliver agents including high-molecular weight DNA into the skin. Compounds including analgesics, antibodies, hormones and high-molecular weight DNAs have been administered to the skin. The majority of applications resulted in the targeting of the upper epidermis.

Liposomes fall into two broad classes. Cationic liposomes are positively charged liposomes which interact with the negatively charged DNA molecules to form a stable complex. The positively charged DNA/liposome complex binds to the negatively charged cell surface and is internalized in an endosome. Due to the acidic pH within the endosome, the liposomes are ruptured, releasing their contents into the cell cytoplasm (Wang et al., Biochem. Biophys. Res. Commun., 1987, 147, 980-985).

Liposomes which are pH-sensitive or negatively-charged, entrap DNA rather than complex with it. Since both the DNA and the lipid are similarly charged, repulsion rather than complex formation occurs. Nevertheless, some DNA is entrapped within the aqueous interior of these liposomes. pH-sensitive liposomes have been used to deliver DNA encoding the thymidine kinase gene to cell monolayers in culture. Expression of the exogenous gene was detected in the target cells (Zhou et al., Journal of Controlled Release, 1992, 19, 269-274).

One major type of liposomal composition includes phospholipids other than naturally-derived phosphatidylcholine. Neutral liposome compositions, for example, can be formed from dimyristoyl phosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC). Anionic liposome compositions generally are formed from dimyristoyl phosphatidylglycerol, while anionic fusogenic liposomes are formed primarily from dioleoyl phosphatidylethanolamine (DOPE). Another type of liposomal composition is formed from phosphatidylcholine (PC) such as, for example, soybean PC, and egg PC. Another type is formed from mixtures of phospholipid and/or phosphatidylcholine and/or cholesterol.

Several studies have assessed the topical delivery of liposomal drug formulations to the skin. Application of liposomes containing interferon to guinea pig skin resulted in a reduction of skin herpes sores while delivery of interferon via other means (e.g. as a solution or as an emulsion) were ineffective (Weiner et al., Journal of Drug Targeting, 1992, 2, 405-410). Further, an additional study tested the efficacy of interferon administered as part of a liposomal formulation to the administration of interferon using an aqueous system, and concluded that the liposomal formulation was superior to aqueous administration (du Plessis et al., Antiviral Research, 1992, 18, 259-265).

Non-ionic liposomal systems have also been examined to determine their utility in the delivery of drugs to the skin, in particular systems comprising non-ionic surfactant and cholesterol. Non-ionic liposomal formulations comprising Novasome™ I (glyceryl dilaurate/cholesterol/polyoxyethylene-10-stearyl ether) and Novasome™ II (glyceryl distearate/cholesterol/polyoxyethylene-10-stearyl ether) were used to deliver cyclosporin-A into the dermis of mouse skin. Results indicated that such non-ionic liposomal systems were effective in facilitating the deposition of cyclosporin-A into different layers of the skin (Hu et al. S.T.P.Pharma. Sci., 1994, 4, 6, 466).

Liposomes also include “sterically stabilized” liposomes, a term which, as used herein, refers to liposomes comprising one or more specialized lipids that, when incorporated into liposomes, result in enhanced circulation lifetimes relative to liposomes lacking such specialized lipids. Examples of sterically stabilized liposomes are those in which part of the vesicle-forming lipid portion of the liposome (A) comprises one or more glycolipids, such as monosialoganglioside G _M1or (B) is derivatized with one or more hydrophilic polymers, such as a polyethylene glycol (PEG) moiety. While not wishing to be bound by any particular theory, it is thought in the art that, at least for sterically stabilized liposomes containing gangliosides, sphingomyelin, or PEG-derivatized lipids, the enhanced circulation half-life of these sterically stabilized liposomes derives from a reduced uptake into cells of the reticuloendothelial system (RES) (Allen et al., FEBS Letters, 1987, 223, 42; Wu et al., Cancer Research, 1993, 53, 3765).

Various liposomes comprising one or more glycolipids are known in the art. Papahadjopoulos et al. ( Ann. N.Y. Acad. Sci., 1987, 507, 64) reported the ability of monosialoganglioside G_M1, galactocerebroside sulfate and phosphatidylinositol to improve blood half-lives of liposomes. These findings were expounded upon by Gabizon et al. (Proc. Natl. Acad. Sci. U.S.A., 1988, 85, 6949). U.S. Pat. No. 4,837,028 and WO 88/04924, both to Allen et al., disclose liposomes comprising (1) sphingomyelin and (2) the ganglioside G_M1or a galactocerebroside sulfate ester. U.S. Pat. No. 5,543,152 (Webb et al.) discloses liposomes comprising sphingomyelin. Liposomes comprising 1,2-sn-dimyristoylphosphatidylcholine are disclosed in WO 97/13499 (Lim et al.).

Many liposomes comprising lipids derivatized with one or more hydrophilic polymers, and methods of preparation thereof, are known in the art. Sunamoto et al. ( Bull. Chem. Soc. Jpn., 1980, 53, 2778) described liposomes comprising a nonionic detergent, 2C₁₂15G, that contains a PEG moiety. Illum et al. (FEBS Lett., 1984, 167, 79) noted that hydrophilic coating of polystyrene particles with polymeric glycols results in significantly enhanced blood half-lives. Synthetic phospholipids modified by the attachment of carboxylic groups of polyalkylene glycols (e.g., PEG) are described by Sears (U.S. Pat. Nos. 4,426,330 and 4,534,899). Klibanov et al. (FEBS Lett., 1990, 268, 235) described experiments demonstrating that liposomes comprising phosphatidylethanolamine (PE) derivatized with PEG or PEG stearate have significant increases in blood circulation half-lives. Blume et al. (Biochimica et Biophysica Acta, 1990, 1029, 91) extended such observations to other PEG-derivatized phospholipids, e.g., DSPE-PEG, formed from the combination of distearoylphosphatidylethanolamine (DSPE) and PEG. Liposomes having covalently bound PEG moieties on their external surface are described in European Patent No. EP 0 445 131 B1 and WO 90/04384 to Fisher. Liposome compositions containing 1-20 mole percent of PE derivatized with PEG, and methods of use thereof, are described by Woodle et al. (U.S. Pat. Nos. 5,013,556 and 5,356,633) and Martin et al. (U.S. Pat. No. 5,213,804 and European Patent No. EP 0 496 813 B1). Liposomes comprising a number of other lipid-polymer conjugates are disclosed in WO 91/05545 and U.S. Pat. No. 5,225,212 (both to Martin et al.) and in WO 94/20073 (Zalipsky et al.) Liposomes comprising PEG-modified ceramide lipids are described in WO 96/10391 (Choi et al.). U.S. Pat. Nos. 5,540,935 (Miyazaki et al.) and 5,556,948 (Tagawa et al.) describe PEG-containing liposomes that can be further derivatized with functional moieties on their surfaces.

A limited number of liposomes comprising nucleic acids are known in the art. WO 96/40062 to Thierry et al. discloses methods for encapsulating high molecular weight nucleic acids in liposomes. U.S. Pat. No. 5,264,221 to Tagawa et al. discloses protein-bonded liposomes and asserts that the contents of such liposomes may include an antisense RNA. U.S. Pat. No. 5,665,710 to Rahman et al. describes certain methods of encapsulating oligodeoxynucleotides in liposomes. WO 97/04787 to Love et al. discloses liposomes comprising antisense oligonucleotides targeted to the raf gene.

Transfersomes are yet another type of liposomes, and are highly deformable lipid aggregates which are attractive candidates for drug delivery vehicles. Transfersomes may be described as lipid droplets which are so highly deformable that they are easily able to penetrate through pores which are smaller than the droplet. Transfersomes are adaptable to the environment in which they are used, e.g. they are self-optimizing (adaptive to the shape of pores in the skin), self-repairing, frequently reach their targets without fragmenting, and often self-loading. To make transfersomes it is possible to add surface edge-activators, usually surfactants, to a standard liposomal composition. Transfersomes have been used to deliver serum albumin to the skin. The transfersome-mediated delivery of serum albumin has been shown to be as effective as subcutaneous injection of a solution containing serum albumin.

Surfactants find wide application in formulations such as emulsions (including microemulsions) and liposomes. The most common way of classifying and ranking the properties of the many different types of surfactants, both natural and synthetic, is by the use of the hydrophile/lipophile balance (HLB). The nature of the hydrophilic group (also known as the “head”) provides the most useful means for categorizing the different surfactants used in formulations (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988, p. 285).

If the surfactant molecule is not ionized, it is classified as a nonionic surfactant. Nonionic surfactants find wide application in pharmaceutical and cosmetic products and are usable over a wide range of pH values. In general their HLB values range from 2 to about 18 depending on their structure. Nonionic surfactants include nonionic esters such as ethylene glycol esters, propylene glycol esters, glyceryl esters, polyglyceryl esters, sorbitan esters, sucrose esters, and ethoxylated esters. Nonionic alkanolamides and ethers such as fatty alcohol ethoxylates, propoxylated alcohols, and ethoxylated/propoxylated block polymers are also included in this class. The polyoxyethylene surfactants are the most popular members of the nonionic surfactant class.

If the surfactant molecule carries a negative charge when it is dissolved or dispersed in water, the surfactant is classified as anionic. Anionic surfactants include carboxylates such as soaps, acyl lactylates, acyl amides of amino acids, esters of sulfuric acid such as alkyl sulfates and ethoxylated alkyl sulfates, sulfonates such as alkyl benzene sulfonates, acyl isethionates, acyl taurates and sulfosuccinates, and phosphates. The most important members of the anionic surfactant class are the alkyl sulfates and the soaps.

If the surfactant molecule carries a positive charge when it is dissolved or dispersed in water, the surfactant is classified as cationic. Cationic surfactants include quaternary ammonium salts and ethoxylated amines. The quaternary ammonium salts are the most used members of this class.

If the surfactant molecule has the ability to carry either a positive or negative charge, the surfactant is classified as amphoteric. Amphoteric surfactants include acrylic acid derivatives, substituted alkylamides, N-alkylbetaines and phosphatides.

The use of surfactants in drug products, formulations and in emulsions has been reviewed (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988, p. 285).

Penetration Enhancers

In one embodiment, the present invention employs various penetration enhancers to effect the efficient delivery of nucleic acids, particularly oligonucleotides, to the skin of animals. Most drugs are present in solution in both ionized and nonionized forms. However, usually only lipid soluble or lipophilic drugs readily cross cell membranes. It has been discovered that even non-lipophilic drugs may cross cell membranes if the membrane to be crossed is treated with a penetration enhancer. In addition to aiding the diffusion of non-lipophilic drugs across cell membranes, penetration enhancers also enhance the permeability of lipophilic drugs.

Penetration enhancers may be classified as belonging to one of five broad categories, i.e., surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92). Each of the above mentioned classes of penetration enhancers are described below in greater detail.

Surfactants: In connection with the present invention, surfactants (or “surface-active agents”) are chemical entities which, when dissolved in an aqueous solution, reduce the surface tension of the solution or the interfacial tension between the aqueous solution and another liquid, with the result that absorption of oligonucleotides through the mucosa is enhanced. In addition to bile salts and fatty acids, these penetration enhancers include, for example, sodium lauryl sulfate, polyoxyethylene-9-lauryl ether and polyoxyethylene-20-cetyl ether) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92); and perfluorochemical emulsions, such as FC-43. Takahashi et al., J. Pharm. Pharmacol., 1988, 40, 252).

Fatty acids: Various fatty acids and their derivatives which act as penetration enhancers include, for example, oleic acid, lauric acid, capric acid (n-decanoic acid), myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein (1-monooleoyl-rac-glycerol), dilaurin, caprylic acid, arachidonic acid, glycerol 1-monocaprate, 1-dodecylazacycloheptan-2-one, acylcarnitines, acylcholines, C _1-10alkyl esters thereof (e.g., methyl, isopropyl and t-butyl), and mono- and di-glycerides thereof (i.e., oleate, laurate, caprate, myristate, palmitate, stearate, linoleate, etc.) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; El Hariri et al., J. Pharm. Pharmacol., 1992, 44, 651-654).

Bile salts: The physiological role of bile includes the facilitation of dispersion and absorption of lipids and fat-soluble vitamins (Brunton, Chapter 38 in: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Ed., Hardman et al. Eds., McGraw-Hill, New York, 1996, pp. 934-935). Various natural bile salts, and their synthetic derivatives, act as penetration enhancers. Thus the term “bile salts”, includes any of the naturally occurring components of bile as well as any of their synthetic derivatives. The bile salts of the invention include, for example, cholic acid (or its pharmaceutically acceptable sodium salt, sodium cholate), dehydrocholic acid (sodium dehydrocholate), deoxycholic acid (sodium deoxycholate), glucholic acid (sodium glucholate), glycholic acid (sodium glycocholate), glycodeoxycholic acid (sodium glycodeoxycholate), taurocholic acid (sodium taurocholate), taurodeoxycholic acid (sodium taurodeoxycholate), chenodeoxycholic acid (sodium chenodeoxycholate), ursodeoxycholic acid (UDCA), sodium tauro-24,25-dihydro-fusidate (STDHF), sodium glycodihydrofusidate and polyoxyethylene-9-lauryl ether (POE) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Swinyard, Chapter 39 In: Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, Pa., 1990, pages 782-783; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Yamamoto et al., J. Pharm. Exp. Ther., 1992, 263, 25; Yamashita et al., J. Pharm. Sci., 1990, 79, 579-583).

Chelating Agents: Chelating agents, as used in connection with the present invention, can be defined as compounds that remove metallic ions from solution by forming complexes therewith, with the result that absorption of oligonucleotides through the mucosa is enhanced. With regards to their use as penetration enhancers in the present invention, chelating agents have the added advantage of also serving as DNase inhibitors, as most characterized DNA nucleases require a divalent metal ion for catalysis and are thus inhibited by chelating agents (Jarrett, J. Chromatogr., 1993, 618, 315-339). Chelating agents of the invention include but are not limited to disodium ethylenediaminetetraacetate (EDTA), citric acid, salicylates (e.g., sodium salicylate, 5-methoxysalicylate and homovanilate), N-acyl derivatives of collagen, laureth-9 and N-amino acyl derivatives of beta-diketones (enamines)(Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Buur et al., J. Control Rel., 1990, 14, 43-51).

Non-chelating non-surfactants: As used herein, non-chelating non-surfactant penetration enhancing compounds can be defined as compounds that demonstrate insignificant activity as chelating agents or as surfactants but that nonetheless enhance absorption of oligonucleotides through the alimentary mucosa (Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33). This class of penetration enhancers include, for example, unsaturated cyclic ureas, 1-alkyl- and 1-alkenylazacyclo-alkanone derivatives (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92); and non-steroidal anti-inflammatory agents such as diclofenac sodium, indomethacin and phenylbutazone (Yamashita et al., J. Pharm. Pharmacol., 1987, 39, 621-626).

Agents that enhance uptake of oligonucleotides at the cellular level may also be added to the pharmaceutical and other compositions of the present invention. For example, cationic lipids, such as lipofectin (Junichi et al, U.S. Pat. No. 5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (Lollo et al., PCT Application WO 97/30731), are also known to enhance the cellular uptake of oligonucleotides.

Other agents may be utilized to enhance the penetration of the administered nucleic acids, including glycols such as ethylene glycol and propylene glycol, pyrrols such as 2-pyrrol, azones, and terpenes such as limonene and menthone.

Carriers

Certain compositions of the present invention also incorporate carrier compounds in the formulation. As used herein, “carrier compound” or “carrier” can refer to a nucleic acid, or analog thereof, which is inert (i.e., does not possess biological activity per se) but is recognized as a nucleic acid by in vivo processes that reduce the bioavailability of a nucleic acid having biological activity by, for example, degrading the biologically active nucleic acid or promoting its removal from circulation. The coadministration of a nucleic acid and a carrier compound, typically with an excess of the latter substance, can result in a substantial reduction of the amount of nucleic acid recovered in the liver, kidney or other extracirculatory reservoirs, presumably due to competition between the carrier compound and the nucleic acid for a common receptor. For example, the recovery of a partially phosphorothioate oligonucleotide in hepatic tissue can be reduced when it is coadministered with polyinosinic acid, dextran sulfate, polycytidic acid or 4-acetamido-4′isothiocyano-stilbene-2,2′-disulfonic acid (Miyao et al., Antisense Res. Dev., 1995, 5, 115-121; Takakura et al., Antisense & Nucl. Acid Drug Dev., 1996, 6, 177-183).

Excipients

In contrast to a carrier compound, a “pharmaceutical carrier” or “excipient” is a pharmaceutically acceptable solvent, suspending agent or any other pharmacologically inert vehicle for delivering one or more nucleic acids to an animal. The excipient may be liquid or solid and is selected, with the planned manner of administration in mind, so as to provide for the desired bulk, consistency, etc., when combined with a nucleic acid and the other components of a given pharmaceutical composition. Typical pharmaceutical carriers include, but are not limited to, binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose, etc.); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calcium hydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metallic stearates, hydrogenated vegetable oils, corn starch, polyethylene glycols, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, etc.); and wetting agents (e.g., sodium lauryl sulphate, etc.).

Pharmaceutically acceptable organic or inorganic excipient suitable for non-parenteral administration which do not deleteriously react with nucleic acids can also be used to formulate the compositions of the present invention. Suitable pharmaceutically acceptable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.

Formulations for topical administration of nucleic acids may include sterile and non-sterile aqueous solutions, non-aqueous solutions in common solvents such as alcohols, or solutions of the nucleic acids in liquid or solid oil bases. The solutions may also contain buffers, diluents and other suitable additives. Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration which do not deleteriously react with nucleic acids can be used.

Suitable pharmaceutically acceptable excipients include, but are not limited to, water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.

Other Components

The compositions of the present invention may additionally contain other adjunct components conventionally found in pharmaceutical compositions, at their art-established usage levels. Thus, for example, the compositions may contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms of the compositions of the present invention, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present invention. The formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and/or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation.

Aqueous suspensions may contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers.

Certain embodiments of the invention provide pharmaceutical compositions containing (a) one or more antisense compounds and (b) one or more other chemotherapeutic agents which function by a non-antisense mechanism. Examples of such chemotherapeutic agents include but are not limited to daunorubicin, daunomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, esorubicin, bleomycin, mafosfamide, ifosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, busulfan, mitomycin C, actinomycin D, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, procarbazine, hexamethylmelamine, pentamethylmelamine, mitoxantrone, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards, melphalan, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-azacytidine, hydroxyurea, deoxycoformycin, 4-hydroxyperoxycyclophosphoramide, 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (5-FUdR), methotrexate (MTX), colchicine, taxol, vincristine, vinblastine, etoposide (VP-16), trimetrexate, irinotecan, topotecan, gemcitabine, teniposide, cisplatin and diethylstilbestrol (DES). See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed. 1987, pp. 1206-1228, Berkow et al., eds., Rahway, N.J. When used with the compounds of the invention, such chemotherapeutic agents may be used individually (e.g., 5-FU and oligonucleotide), sequentially (e.g., 5-FU and oligonucleotide for a period of time followed by MTX and oligonucleotide), or in combination with one or more other such chemotherapeutic agents (e.g., 5-FU, MTX and oligonucleotide, or 5-FU, radiotherapy and oligonucleotide). Anti-inflammatory drugs, including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, may also be combined in compositions of the invention. See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 2499-2506 and 46-49, respectively). Other non-antisense chemotherapeutic agents are also within the scope of this invention. Two or more combined compounds may be used together or sequentially.

In another related embodiment, compositions of the invention may contain one or more antisense compounds, particularly oligonucleotides, targeted to a first nucleic acid and one or more additional antisense compounds targeted to a second nucleic acid target. Numerous examples of antisense compounds are known in the art. Two or more combined compounds may be used together or sequentially.

The formulation of therapeutic compositions and their subsequent administration is believed to be within the skill of those in the art. Dosing is dependent on severity and responsiveness of the disease state to be treated, with the course of treatment lasting from several days to several months, or until a cure is effected or a diminution of the disease state is achieved. Optimal dosing schedules can be calculated from measurements of drug accumulation in the body of the patient. Persons of ordinary skill can easily determine optimum dosages, dosing methodologies and repetition rates. Optimum dosages may vary depending on the relative potency of individual oligonucleotides, and can generally be estimated based on EC ₅₀s found to be effective in in vitro and in vivo animal models. In general, dosage is from 0.01 ug to 100 g per kg of body weight, and may be given once or more daily, weekly, monthly or yearly, or even once every 2 to 20 years. Persons of ordinary skill in the art can easily estimate repetition rates for dosing based on measured residence times and concentrations of the drug in bodily fluids or tissues. Following successful treatment, it may be desirable to have the patient undergo maintenance therapy to prevent the recurrence of the disease state, wherein the oligonucleotide is administered in maintenance doses, ranging from 0.01 ug to 100 g per kg of body weight, once or more daily, to once every 20 years.

While the present invention has been described with specificity in accordance with certain of its preferred embodiments, the following examples serve only to illustrate the invention and are not intended to limit the same.

EXAMPLES

Example 1

Nucleoside Phosphoramidites for Oligonucleotide Synthesis Deoxy and 2′-alkoxy Amidites [0136]
2′-Deoxy and 2′-methoxy beta-cyanoethyldiisopropyl phosphoramidites were purchased from commercial sources (e.g. Chemgenes, Needham MA or Glen Research, Inc. Sterling Va.). Other 2′-O-alkoxy substituted nucleoside amidites are prepared as described in U.S. Pat. No. 5,506,351, herein incorporated by reference. For oligonucleotides synthesized using 2′-alkoxy amidites, the standard cycle for unmodified oligonucleotides was utilized, except the wait step after pulse delivery of tetrazole and base was increased to 360 seconds. [0137]
Oligonucleotides containing 5-methyl-2′-deoxycytidine (5-Me-C) nucleotides were synthesized according to published methods [Sanghvi, et. al., [0138] Nucleic Acids Research, 1993, 21, 3197-3203] using commercially available phosphoramidites (Glen Research, Sterling Va. or ChemGenes, Needham Mass.).
2′-Fluoro Amidites [0139]
2′-Fluorodeoxyadenosine Amidites [0140]
2′-fluoro oligonucleotides were synthesized as described previously [Kawasaki, et. al., [0141] J. Med. Chem., 1993, 36, 831-841] and U.S. Pat. No. 5,670,633, herein incorporated by reference. Briefly, the protected nucleoside N6-benzoyl-2′-deoxy-2′-fluoroadenosine was synthesized utilizing commercially available 9-beta-D-arabinofuranosyladenine as starting material and by modifying literature procedures whereby the 2′-alpha-fluoro atom is introduced by a S_N2-displacement of a 2′-beta-trityl group. Thus N6-benzoyl-9beta-D-arabinofuranosyladenine was selectively protected in moderate yield as the 3′,5′-ditetrahydropyranyl (THP) intermediate. Deprotection of the THP and N6-benzoyl groups was accomplished using standard methodologies and standard methods were used to obtain the 5¹-dimethoxytrityl-(DMT) and 5′-DMT-3′-phosphoramidite intermediates.
2′-Fluorodeoxyguanosine [0142]
The synthesis of 2′-deoxy-2′-fluoroguanosine was accomplished using tetraisopropyldisiloxanyl (TPDS) protected 9-beta-D-arabinofuranosylguanine as starting material, and conversion to the intermediate diisobutyryl-arabinofuranosylguanosine. Deprotection of the TPDS group was followed by protection of the hydroxyl group with THP to give diisobutyryl di-THP protected arabinofuranosylguanine. Selective O-deacylation and triflation was followed by treatment of the crude product with fluoride, then deprotection of the THP groups. Standard methodologies were used to obtain the 5′-DMT- and 5′-DMT-3′-phosphoramidites. [0143]
2′-Fluorouridine [0144]
Synthesis of 2′-deoxy-2[0145] ¹-fluorouridine was accomplished by the modification of a literature procedure in which 2,2′-anhydro-1-beta-D-arabinofuranosyluracil was treated with 70% hydrogen fluoride-pyridine. Standard procedures were used to obtain the 5′-DMT and 5′-DMT-3′phosphoramidites.
2′-Fluorodeoxycytidine [0146]
2′-deoxy-2′-fluorocytidine was synthesized via amination of 2′-deoxy-2′-fluorouridine, followed by selective protection to give N4-benzoyl-2′-deoxy-2′-fluorocytidine. Standard procedures were used to obtain the 5′-DMT and 5′-DMT-3′phosphoramidites. [0147]
2′-O-(2-Methoxyethyl) Modified Amidites [0148]
2′-O-Methoxyethyl-substituted nucleoside amidites are prepared as follows, or alternatively, as per the methods of Martin, P., [0149] Helvetica Chimica Acta, 1995, 78, 486-504.
2,2′-Anhydro[1-(beta-D-arabinofuranosyl)-5-methyluridine][0150]
5-Methyluridine (ribosylthymine, commercially available through Yamasa, Choshi, Japan) (72.0 g, 0.279 M), diphenyl-carbonate (90.0 g, 0.420 M) and sodium bicarbonate (2.0 g, 0.024 M) were added to DMF (300 mL). The mixture was heated to reflux, with stirring, allowing the evolved carbon dioxide gas to be released in a controlled manner. After 1 hour, the slightly darkened solution was concentrated under reduced pressure. The resulting syrup was poured into diethylether (2.5 L), with stirring. The product formed a gum. The ether was decanted and the residue was dissolved in a minimum amount of methanol (ca. 400 mL). The solution was poured into fresh ether (2.5 L) to yield a stiff gum. The ether was decanted and the gum was dried in a vacuum oven (60° C. at 1 mm Hg for 24 h) to give a solid that was crushed to a light tan powder (57 g, 85% crude yield). The NMR spectrum was consistent with the structure, contaminated with phenol as its sodium salt (ca. 5%). The material was used as is for further reactions (or it can be purified further by column chromatography using a gradient of methanol in ethyl acetate (10-25%) to give a white solid, mp 222-4° C.). [0151]
2′-O-Methoxyethyl-5-methyluridine [0152]
2,2′-Anhydro-5-methyluridine (195 g, 0.81 M), tris(2-methoxyethyl)borate (231 g, 0.98 M) and 2-methoxyethanol (1.2 L) were added to a 2 L stainless steel pressure vessel and placed in a pre-heated oil bath at 1600C. After heating for 48 hours at 155-160° C., the vessel was opened and the solution evaporated to dryness and triturated with MeOH (200 mL). The residue was suspended in hot acetone (1 L). The insoluble salts were filtered, washed with acetone (150 mL) and the filtrate evaporated. The residue (280 g) was dissolved in CH[0153] ₃CN (600 mL) and evaporated. A silica gel column (3 kg) was packed in CH₂Cl₂/acetone/MeOH (20:5:3) containing 0.5% Et₃NH. The residue was dissolved in CH₂C1₂(250 mL) and adsorbed onto silica (150 g) prior to loading onto the column. The product was eluted with the packing solvent to give 160 g (63%) of product. Additional material was obtained by reworking impure fractions.
2′-O-Methoxyethyl-5′-O-dimethoxytrityl-5-methyluridine [0154]
2′-O-Methoxyethyl-5-methyluridine (160 g, 0.506 M) was co-evaporated with pyridine (250 mL) and the dried residue dissolved in pyridine (1.3 L). A first aliquot of dimethoxytrityl chloride (94.3 g, 0.278 M) was added and the mixture stirred at room temperature for one hour. A second aliquot of dimethoxytrityl chloride (94.3 g, 0.278 M) was added and the reaction stirred for an additional one hour. Methanol (170 mL) was then added to stop the reaction. HPLC showed the presence of approximately 70% product. The solvent was evaporated and triturated with CH[0155] ₃CN (200 mL) The residue was dissolved in CHCl₃(1.5 L) and extracted with 2×500 mL of saturated NaHCO₃and 2×500 mL of saturated NaCl. The organic phase was dried over Na₂SO₄, filtered and evaporated. 275 g of residue was obtained. The residue was purified on a 3.5 kg silica gel column, packed and eluted with EtOAc/hexane/acetone (5:5:1) containing 0.5% Et₃NH. The pure fractions were evaporated to give 164 g of product. Approximately 20 g additional was obtained from the impure fractions to give a total yield of 183 g (57%).
3′-O-Acetyl-2′-O-methoxyethyl-5′-O-dimethoxytrityl-5-methyluridine [0156]
2′-O-Methoxyethyl-5′-O-dimethoxytrityl-5-methyluridine (106 g, 0.167 M), DMF/pyridine (750 mL of a 3:1 mixture prepared from 562 mL of DMF and 188 mL of pyridine) and acetic anhydride (24.38 mL, 0.258 M) were combined and stirred at room temperature for 24 hours. The reaction was monitored by TLC by first quenching the TLC sample with the addition of MeOH. Upon completion of the reaction, as judged by TLC, MeOH (50 mL) was added and the mixture evaporated at 35° C. The residue was dissolved in CHCl[0157] ₃(800 mL) and extracted with 2×200 mL of saturated sodium bicarbonate and 2×200 mL of saturated NaCl. The water layers were back extracted with 200 mL of CHCl₃. The combined organics were dried with sodium sulfate and evaporated to give 122 g of residue (approx. 90% product). The residue was purified on a 3.5 kg silica gel column and eluted using EtOAc/hexane(4:1). Pure product fractions were evaporated to yield 96 g (84%). An additional 1.5 g was recovered from later fractions.
3∵-O-Acetyl-2′-O-methoxyethyl-5′-O-dimethoxytrityl-5-methyl-4-triazoleuridine [0158]
A first solution was prepared by dissolving 3′-O-acetyl-2′-O-methoxyethyl-5′-O-dimethoxytrityl-5-methyluridine (96 g, 0.144 M) in CH[0159] ₃CN (700 mL) and set aside. Triethylamine (189 mL, 1.44 M) was added to a solution of triazole (90 g, 1.3 M) in CH₃CN (1 L), cooled to −50C and stirred for 0.5 h using an overhead stirrer. POCl₃was added dropwise, over a 30 minute period, to the stirred solution maintained at O-10° C., and the resulting mixture stirred for an additional 2 hours. The first solution was added dropwise, over a 45 minute period, to the latter solution. The resulting reaction mixture was stored overnight in a cold room. Salts were filtered from the reaction mixture and the solution was evaporated. The residue was dissolved in EtOAc (1 L) and the insoluble solids were removed by filtration. The filtrate was washed with 1×300 mL of NaHCO₃and 2×300 mL of saturated NaCl, dried over sodium sulfate and evaporated. The residue was triturated with EtOAc to give the title compound.
2′-O-Methoxyethyl-5′-O-dimethoxytrityl-5-methylcytidine [0160]
A solution of 3′-O-acetyl-2′-O-methoxyethyl-5′-O-dimethoxytrityl-5-methyl-4-triazoleuridine (103 g, 0.141 M) in dioxane (500 mL) and NH[0161] ₄OH (30 mL) was stirred at room temperature for 2 hours. The dioxane solution was evaporated and the residue azeotroped with MeOH (2×200 mL). The residue was dissolved in MeOH (300 mL) and transferred to a 2 liter stainless steel pressure vessel. MeOH (400 mL) saturated with NH₃gas was added and the vessel heated to 100° C. for 2 hours (TLC showed complete conversion). The vessel contents were evaporated to dryness and the residue was dissolved in EtOAc (500 mL) and washed once with saturated NaCl (200 mL). The organics were dried over sodium sulfate and the solvent was evaporated to give 85 g (95%) of the title compound.
N4-Benzoyl-2′-O-methoxyethyl-5′-O-dimethoxytrityl-5-methylcytidine [0162]
2′-O-Methoxyethyl-5′-O-dimethoxytrityl-5-methylcytidine (85 g, 0.134 M) was dissolved in DMF (800 mL) and benzoic anhydride (37.2 g, 0.165 M) was added with stirring. After stirring for 3 hours, TLC showed the reaction to be approximately 95% complete. The solvent was evaporated and the residue azeotroped with MeOH (200 mL). The residue was dissolved in CHCl[0163] ₃(700 mL) and extracted with saturated NaHCO₃(2×300 mL) and saturated NaCl (2×300 mL), dried over MgSO₄and evaporated to give a residue (96 g). The residue was chromatographed on a 1.5 kg silica column using EtOAc/hexane (1:1) containing 0.5% Et₃NH as the eluting solvent. The pure product fractions were evaporated to give 90 g (90%) of the title compound.
N4-Benzoyl-2′-O-methoxyethyl-5′-O-dimethoxytrityl-5-methylcytidine-3′-amidite [0164]
N4-Benzoyl-2′-O-methoxyethyl-5′-O-dimethoxytrityl-5-methylcytidine (74 g, 0.10 M) was dissolved in CH[0165] ₂Cl₂(1 L) Tetrazole diisopropylamine (7.1 g) and 2-cyanoethoxy-tetra-(isopropyl)phosphite (40.5 mL, 0.123 M) were added with stirring, under a nitrogen atmosphere. The resulting mixture was stirred for 20 hours at room temperature (TLC showed the reaction to be 95% complete). The reaction mixture was extracted with saturated NaHCO₃(1×300 mL) and saturated NaCl (3×300 mL). The aqueous washes were back-extracted with CH₂Cl₂(300 mL), and the extracts were combined, dried over MgSO₄and concentrated. The residue obtained was chromatographed on a 1.5 kg silica column using EtOAc/hexane (3:1) as the eluting solvent. The pure fractions were combined to give 90.6 g (87%) of the title compound.
2[0166] ¹-O-(Aminooxyethyl) nucleoside amidites and 2′-O-(dimethylaminooxyethyl) Nucleoside Amidites
2′-(Dimethylaminooxyethoxy) Nucleoside Amidites [0167]
2′-(Dimethylaminooxyethoxy) nucleoside amidites [also known in the art as 2′-O-(dimethylaminooxyethyl) nucleoside amidites] are prepared as described in the following paragraphs. Adenosine, cytidine and guanosine nucleoside amidites are prepared similarly to the thymidine (5-methyluridine) except the exocyclic amines are protected with a benzoyl moiety in the case of adenosine and cytidine and with isobutyryl in the case of guanosine. [0168]
5′-O-tert-Butyldiphenylsilyl-O[0169] ²-2′-anhydro-5-methyluridine
O[0170] ²-2-anhydro-5-methyluridine (Pro. Bio. Sint., Varese, Italy, 100.0 g, 0.416 mmol), dimethylaminopyridine (0.66 g, 0.013 eq, 0.0054 mmol) were dissolved in dry pyridine (500 ml) at ambient temperature under an argon atmosphere and with mechanical stirring. tert-Butyldiphenylchlorosilane (125.8 g, 119.0 mL, 1.1 eq, 0.458 mmol) was added in one portion. The reaction was stirred for 16 h at ambient temperature. TLC (Rf 0.22, ethyl acetate) indicated a complete reaction. The solution was concentrated under reduced pressure to a thick oil. This was partitioned between dichloromethane (1 L) and saturated sodium bicarbonate (2×1 L) and brine (1 L). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to a thick oil. The oil was dissolved in a 1:1 mixture of ethyl acetate and ethyl ether (600 mL) and the solution was cooled to −10° C. The resulting crystalline product was collected by filtration, washed with ethyl ether (3×200 mL) and dried (40° C., 1 mm Hg, 24 h) to 149g (74.8%) of white solid. TLC and NMR were consistent with pure product.
5′-O-tert-Butyldiphenylsilyl-2′-O-(2-hydroxyethyl)-5-methyluridine [0171]
In a 2 L stainless steel, unstirred pressure reactor was added borane in tetrahydrofuran (1.0 M, 2.0 eq, 622 mL). In the fume hood and with manual stirring, ethylene glycol (350 mL, excess) was added cautiously at first until the evolution of hydrogen gas subsided. 5′-O-tert-Butyldiphenylsilyl-O[0172] ²-2′-anhydro-5-methyluridine (149 g, 0.311 mol) and sodium bicarbonate (0.074 g, 0.003 eq) were added with manual stirring. The reactor was sealed and heated in an oil bath until an internal temperature of 160° C. was reached and then maintained for 16 h (pressure <100 psig). The reaction vessel was cooled to ambient and opened. TLC (Rf 0.67 for desired product and Rf 0.82 for ara-T side product, ethyl acetate) indicated about 70% conversion to the product. In order to avoid additional side product formation, the reaction was stopped, concentrated under reduced pressure (10 to 1 mm Hg) in a warm water bath (40-100° C.) with the more extreme conditions used to remove the ethylene glycol. [Alternatively, once the low boiling solvent is gone, the remaining solution can be partitioned between ethyl acetate and water. The product will be in the organic phase.] The residue was purified by column chromatography (2 kg silica gel, ethyl acetate-hexanes gradient 1:1 to 4:1). The appropriate fractions were combined, stripped and dried to product as a white crisp foam (84g, 50%), contaminated starting material (17.4 g) and pure reusable starting material 20 g. The yield based on starting material less pure recovered starting material was 58%. TLC and NMR were consistent with 99% pure product.
2′-O-([2-phthalimidoxy)ethyl]-5′-t-butyldiphenylsilyl-5-methyluridine [0173]
5′-O-tert-Butyldiphenylsilyl-2′-O-(2-hydroxyethyl)-5-methyluridine (20g, 36.98 mmol) was mixed with triphenylphosphine (11.63g, 44.36 mmol) and N-hydroxyphthalimide (7.24g, 44.36 mmol). It was then dried over P[0174] ₂O₅under high vacuum for two days at 40° C. The reaction mixture was flushed with argon and dry THF (369.8 mL, Aldrich, sure seal bottle) was added to get a clear solution. Diethyl-azodicarboxylate (6.98 mL, 44.36 mmol) was added dropwise to the reaction mixture. The rate of addition is maintained such that resulting deep red coloration is just discharged before adding the next drop. After the addition was complete, the reaction was stirred for 4 hrs. By that time TLC showed the completion of the reaction (ethylacetate:hexane, 60:40). The solvent was evaporated in vacuum. Residue obtained was placed on a flash column and eluted with ethyl acetate:hexane (60:40), to get 2′-O-([2-phthalimidoxy)ethyl]-5′-t-butyldiphenylsilyl-5-methyluridine as white foam (21.819 g, 86%).
5′-O-tert-butyldiphenylsilyl-2′-O-[(2-formadoximinooxy)ethyl]-5-methyluridine [0175]
2′-O-([2-phthalimidoxy)ethyl]-5′-t-butyldiphenylsilyl-5-methyluridine (3.1g, 4.5 mmol) was dissolved in dry CH[0176] ₂Cl₂(4.5 mL) and methylhydrazine (300 mL, 4.64 mmol) was added dropwise at −100C to 0° C. After 1 h the mixture was filtered, the filtrate was washed with ice cold CH₂Cl₂and the combined organic phase was washed with water, brine and dried over anhydrous Na₂SO₄. The solution was concentrated to get 2′-O-(aminooxyethyl) thymidine, which was then dissolved in MeOH (67.5 mL). To this formaldehyde (20% aqueous solution, w/w, 1.1 eq.) was added and the resulting mixture was strirred for 1 h. Solvent was removed under vacuum; residue chromatographed to get 5′-O-tert-butyldiphenylsilyl-2′-O-[(2-formadoximinooxy) ethyl]-5-methyluridine as white foam (1.95 g, 78%)
5′-O-tert-Butyldiphenylsilyl-2′-O-[N,N-dimethylaminooxyethyl]-5-methyluridine [0177]
5′-O-tert-butyldiphenylsilyl-2′-O-[(2-formadoximinooxy)ethyl]-5-methyluridine (1.77g, 3. 12 mmol) was dissolved in a solution of 1M pyridinium p-toluenesulfonate (PPTS) in dry MeOH (30.6 mL). Sodium cyanoborohydride (0.39g, 6.13 mmol) was added to this solution at 10° C. under inert atmosphere. The reaction mixture was stirred for 10 minutes at 10° C. After that the reaction vessel was removed from the ice bath and stirred at room temperature for 2 h, the reaction monitored by TLC (5% MeOH in CH[0178] ₂Cl₂). Aqueous NaHCO₃solution (5%, 10 mL) was added and extracted with ethyl acetate (2×20 mL). Ethyl acetate phase was dried over anhydrous Na₂SO₄, evaporated to dryness. Residue was dissolved in a solution of 1M PPTS in MeOH (30.6 mL). Formaldehyde (20% w/w, 30 mL, 3.37 mmol) was added and the reaction mixture was stirred at room temperature for 10 minutes. Reaction mixture cooled to 10° C. in an ice bath, sodium cyanoborohydride (0.39g, 6.13 mmol) was added and reaction mixture stirred at 10° C. for 10 minutes. After 10 minutes, the reaction mixture was removed from the ice bath and stirred at room temperature for 2 hrs. To the reaction mixture 5% NaHCO₃(25 mL) solution was added and extracted with ethyl acetate (2×25 mL). Ethyl acetate layer was dried over anhydrous Na₂SO₄and evaporated to dryness. The residue obtained was purified by flash column chromatography and eluted with 5% MeOH in CH₂Cl₂to get 5′-O-tert-butyldiphenylsilyl-2′-O-[N,N-dimethylaminooxyethyl]-5-methyluridine as a white foam (14.6g, 80%).
2′-O-(dimethylaminooxyethyl)-5-methyluridine [0179]
Triethylamine trihydrofluoride (3.91 mL, 24.0 mmol) was dissolved in dry THF and triethylamine (1.67 mL, 12 mmol, dry, kept over KOH). This mixture of triethylamine-2HF was then added to 5′-O-tert-butyldiphenylsilyl-2′-O-[N,N-dimethylaminooxyethyl]-5-methyluridine (1.40g, 2.4 mmol) and stirred at room temperature for 24 hrs. Reaction was monitored by TLC (5% MeOH in CH[0180] ₂Cl₂). Solvent was removed under vacuum and the residue placed on a flash column and eluted with 10% MeOH in CH₂Cl₂to get 2′-0-(dimethylaminooxyethyl)-5-methyluridine (766 mg, 92.5%).
5′-O-DMT-2′-O-(dimethylaminooxyethyl)-5-methyluridine [0181]
2′-O-(dimethylaminooxyethyl)-5-methyluridine (750 mg, 2.17 mmol) was dried over P[0182] ₂O₅under high vacuum overnight at 40° C. It was then co-evaporated with anhydrous pyridine (20 mL). The residue obtained was dissolved in pyridine (11 mL) under argon atmosphere. 4-dimethylaminopyridine (26.5 mg, 2.60 mmol), 4,4′-dimethoxytrityl chloride (880 mg, 2.60 mmol) was added to the mixture and the reaction mixture was stirred at room temperature until all of the starting material disappeared. Pyridine was removed under vacuum and the residue chromatographed and eluted with 10% MeOH in CH₂C1₂(containing a few drops of pyridine) to get 5′-O-DMT-2′-O-(dimethylamino-oxyethyl)-5-methyluridine (1.13g, 80%).
5′-O-DMT-2′-O-(2-N,N-dimethylaminooxyethyl)-5-methyluridine-3′-[(2-cyanoethyl)-N,N-diisopropylphosphoramidite][0183]
5′-O-DMT-2′-O-(dimethylaminooxyethyl)-5-methyluridine (1.08g, 1.67 mmol) was co-evaporated with toluene (20 mL). To the residue N,N-diisopropylamine tetrazonide (0.29g, 1.67 mmol) was added and dried over P[0184] ₂O₅under high vacuum overnight at 40° C. Then the reaction mixture was dissolved in anhydrous acetonitrile (8.4 mL) and 2-cyanoethyl-N,N,N¹,N¹-tetraisopropylphosphoramidite (2.12 mL, 6.08 mmol) was added. The reaction mixture was stirred at ambient temperature for 4 hrs under inert atmosphere. The progress of the reaction was monitored by TLC (hexane:ethyl acetate 1:1). The solvent was evaporated, then the residue was dissolved in ethyl acetate (70 mL) and washed with 5% aqueous NaHCO₃(40 mL). Ethyl acetate layer was dried over anhydrous Na₂SO₄and concentrated. Residue obtained was chromatographed (ethyl acetate as eluent) to get 5¹-O-DMT-2′-O-(2-N,N-dimethylaminooxyethyl)-5-methyluridine-3′-[(2-cyanoethyl)-N,N-diisopropylphosphoramidite] as a foam (1.04g, 74.9%).
2′-(Aminooxyethoxy) Nucleoside Amidites [0185]
2′-(Aminooxyethoxy) nucleoside amidites [also known in the art as 2′-O-(aminooxyethyl) nucleoside amidites] are prepared as described in the following paragraphs. Adenosine, cytidine and thymidine nucleoside amidites are prepared similarly. [0186]
N2-isobutyryl-6-O-diphenylcarbamoyl-2′-O-(2-ethylacetyl)-5′-O-(4,4′-dimethoxytrityl)guanosine-3′-[(2-cyanoethyl)-N,N-diisopropylphosphoramidite][0187]
The 2′-O-aminooxyethyl guanosine analog may be obtained by selective 2′-O-alkylation of diaminopurine riboside. Multigram quantities of diaminopurine riboside may be purchased from Schering AG (Berlin) to provide 2′-O-(2-ethylacetyl) diaminopurine riboside along with a minor amount of the 3′-O-isomer. 2′-O-(2-ethylacetyl) diaminopurine riboside may be resolved and converted to 2′-O-(2-ethylacetyl)guanosine by treatment with adenosine deaminase. (McGee, D. P. C., Cook, P. D., Guinosso, C. J., WO 94/02501 A1 940203.) Standard protection procedures should afford 2′-O-(2-ethylacetyl)-5′-O-(4,4′-dimethoxytrityl)guanosine and 2-N-isobutyryl-6-O-diphenylcarbamoyl-2′-O-(2-ethylacetyl)-5′-O-(4,4′-dimethoxytrityl)guanosine which may be reduced to provide 2-N-isobutyryl-6-O-diphenylcarbamoyl-2′-O-(2-hydroxyethyl)-5′-O-(4,4′-dimethoxytrityl)guanosine. As before the hydroxyl group may be displaced by N-hydroxyphthalimide via a Mitsunobu reaction, and the protected nucleoside may phosphitylated as usual to yield 2-N-isobutyryl-6-O-diphenylcarbamoyl-2′-O-([2-phthalmidoxy] ethyl)-5′-O-(4,4′-dimethoxytrityl)guanosine-3′-[(2-cyanoethyl)-N,N-diisopropylphosphoramidite][0188]
2′-dimethylaminoethoxyethoxy (2′-DMAEOE) Nucleoside Amidites [0189]
2′-dimethylaminoethoxyethoxy nucleoside amidites (also known in the art as 2′-O-dimethylaminoethoxyethyl, i.e., 2′-O—CH[0190] ₂—O—CH₂—N(CH₂)₂, or 2′-DMAEOE nucleoside amidites) are prepared as follows. Other nucleoside amidites are prepared similarly.
2′-O-[2(2-N,N-dimethylaminoethoxy)ethyl]-5-methyl Uridine [0191]
2[2-(Dimethylamino)ethoxy]ethanol (Aldrich, 6.66 g, 50 mmol) is slowly added to a solution of borane in tetra-hydrofuran (1 M, 10 mL, 10 mmol) with stirring in a 100 mL bomb. Hydrogen gas evolves as the solid dissolves. O[0192] ²—, 2′-anhydro-5-methyluridine (1.2 g, 5 mmol), and sodium bicarbonate (2.5 mg) are added and the bomb is sealed, placed in an oil bath and heated to 155° C. for 26 hours. The bomb is cooled to room temperature and opened. The crude solution is concentrated and the residue partitioned between water (200 mL) and hexanes (200 mL). The excess phenol is extracted into the hexane layer. The aqueous layer is extracted with ethyl acetate (3×200 mL) and the combined organic layers are washed once with water, dried over anhydrous sodium sulfate and concentrated. The residue is columned on silica gel using methanol/methylene chloride 1:20 (which has 2% triethylamine) as the eluent. As the column fractions are concentrated a colorless solid forms which is collected to give the title compound as a white solid.
5′-O-dimethoxytrityl-2′-O-[2(2-N,N-dimethylaminoethoxy)-ethyl)]-5-methyl Uridine [0193]
To 0.5 g (1.3 mmol) of 2′-O-[2(2-N,N-dimethylamino-ethoxy)ethyl)]-5-methyl uridine in anhydrous pyridine (8 mL), triethylamine (0.36 mL) and dimethoxytrityl chloride (DMT-Cl, 0.87 g, 2 eq.) are added and stirred for 1 hour. The reaction mixture is poured into water (200 mL) and extracted with CH[0194] ₂Cl₂(2×200 mL). The combined CH₂Cl₂layers are washed with saturated NaHCO₃solution, followed by saturated NaCl solution and dried over anhydrous sodium sulfate. Evaporation of the solvent followed by silica gel chromatography using MeOH:CH₂Cl₂:Et₃N (20:1, v/v, with 1% triethylamine) gives the title compound.
5′-O-Dimethoxytrityl-2′-O-[2(2-N,N-dimethylaminoethoxy)-ethyl)]-5-methyl uridine-3′-O-(cyanoethyl-N,N-diisopropyl)phosphoramidite [0195]
Diisopropylaminotetrazolide (0.6 g) and 2-cyanoethoxy-N,N-diisopropyl phosphoramidite (1.1 mL, 2 eq.) are added to a solution of 5′-O-dimethoxytrityl-2′-O-[2(2-N,N-dimethylaminoethoxy)ethyl)]-5-methyluridine (2.17 9, 3 mmol) dissolved in CH[0196] ₂Cl₂(20 mL) under an atmosphere of argon. The reaction mixture is stirred overnight and the solvent evaporated. The resulting residue is purified by silica gel flash column chromatography with ethyl acetate as the eluent to give the title compound.

Example 2

Oligonucleotide Synthesis [0197]
Unsubstituted and substituted phosphodiester (P═O) oligonucleotides are synthesized on an automated DNA synthesizer (Applied Biosystems model 380B) using standard phosphoramidite chemistry with oxidation by iodine. [0198]
Phosphorothioates (P═S) are synthesized as for the phosphodiester oligonucleotides except the standard oxidation bottle was replaced by 0.2 M solution of 3H-1,2-benzodithiole-3-one 1,1-dioxide in acetonitrile for the stepwise thiation of the phosphite linkages. The thiation wait step was increased to 68 sec and was followed by the capping step. After cleavage from the CPG column and deblocking in concentrated ammonium hydroxide at 55° C. (18 h), the oligonucleotides were purified by precipitating twice with 2.5 volumes of ethanol from a 0.5 M NaCl solution. Phosphinate oligonucleotides are prepared as described in U.S. Pat. No. 5,508,270, herein incorporated by reference. [0199]
Alkyl phosphonate oligonucleotides are prepared as described in U.S. Pat. No. 4,469,863, herein incorporated by reference. [0200]
3′-Deoxy-3′-methylene phosphonate oligonucleotides are prepared as described in U.S. Pat. Nos. 5,610,289 or 5,625,050, herein incorporated by reference. [0201]
Phosphoramidite oligonucleotides are prepared as described in U.S. Pat. No. 5,256,775 or U.S. Pat. No. 5,366,878, herein incorporated by reference. [0202]
Alkylphosphonothioate oligonucleotides are prepared as described in published PCT applications PCT/US94/00902 and PCT/US93/06976 (published as WO 94/17093 and WO 94/02499, respectively), herein incorporated by reference. [0203]
3′-Deoxy-3′-amino phosphoramidate oligonucleotides are prepared as described in U.S. Pat. No. 5,476,925, herein incorporated by reference. [0204]
Phosphotriester oligonucleotides are prepared as described in U.S. Pat. No. 5,023,243, herein incorporated by reference. [0205]
Borano phosphate oligonucleotides are prepared as described in U.S. Pat. Nos. 5,130,302 and 5,177,198, both herein incorporated by reference. [0206]

Example 3

Oligonucleoside Synthesis [0207]
Methylenemethylimino linked oligonucleosides, also identified as MMI linked oligonucleosides, methylenedimethyl-hydrazo linked oligonucleosides, also identified as MDH linked oligonucleosides, and methylenecarbonylamino linked oligonucleosides, also identified as amide-3 linked oligonucleosides, and methyleneaminocarbonyl linked oligonucleosides, also identified as amide-4 linked oligonucleosides, as well as mixed backbone compounds having, for instance, alternating MMI and P═O or P═S linkages are prepared as described in U.S. Pat. Nos. 5,378,825, 5,386,023, 5,489,677, 5,602,240 and 5,610,289, all of which are herein incorporated by reference. [0208]
Formacetal and thioformacetal linked oligonucleosides are prepared as described in U.S. Pat. Nos. 5,264,562 and 5,264,564, herein incorporated by reference. [0209]
Ethylene oxide linked oligonucleosides are prepared as described in U.S. Pat. No. 5,223,618, herein incorporated by reference. [0210]

Example 4

PNA Synthesis [0211]
Peptide nucleic acids (PNAs) are prepared in accordance with any of the various procedures referred to in Peptide Nucleic Acids (PNA): Synthesis, Properties and Potential Applications, [0212] Bioorganic & Medicinal Chemistry, 1996, 4, 5-23. They may also be prepared in accordance with U.S. Pat. Nos. 5,539,082, 5,700,922, and 5,719,262, herein incorporated by reference.

Example 5

Synthesis of Chimeric Oligonucleotides [0213]
Chimeric oligonucleotides, oligonucleosides or mixed oligonucleotides/oligonucleosides of the invention can be of several different types. These include a first type wherein the “gap” segment of linked nucleosides is positioned between 5′ and 3′ “wing” segments of linked nucleosides and a second “open end” type wherein the “gap” segment is located at either the 3′ or the 5′ terminus of the oligomeric compound. Oligonucleotides of the first type are also known in the art as “gapmers” or gapped oligonucleotides. Oligonucleotides of the second type are also known in the art as “hemimers” or “wingmers”. [0214]
[2′—O—Me]—[2′-deoxy]—[2′-O-Me] Chimeric Phosphorothioate Oligonucleotides [0215]
Chimeric oligonucleotides having 2′-O-alkyl phosphorothioate and 2′-deoxy phosphorothioate oligo-nucleotide segments are synthesized using an Applied Biosystems automated DNA synthesizer Model 380B, as above. oligonucleotides are synthesized using the automated synthesizer and 2′-deoxy-5′-dimethoxytrityl-3′-O-phosphor-amidite for the DNA portion and 5′-dimethoxytrityl-2′-O-methyl-3′-O-phosphoramidite for 51 and 3′ wings. The standard synthesis cycle is modified by increasing the wait step after the delivery of tetrazole and base to 600 s repeated four times for RNA and twice for 2′-O-methyl. The fully protected oligonucleotide is cleaved from the support and the phosphate group is deprotected in 3:1 ammonia/ethanol at room temperature overnight then lyophilized to dryness. Treatment in methanolic ammonia for 24 hrs at room temperature is then done to deprotect all bases and sample was again lyophilized to dryness. The pellet is resuspended in IM TBAF in THF for 24 hrs at room temperature to deprotect the 2′ positions. The reaction is then quenched with 1M TEAA and the sample is then reduced to ½ volume by rotovac before being desalted on a G25 size exclusion column. The oligo recovered is then analyzed spectrophotometrically for yield and for purity by capillary electrophoresis and by mass spectrometry. [0216]
[2′-O-(2-Methoxyethyl)]—[2′-deoxy]—[2′-O-(Methoxyethyl)] Chimeric Phosphorothioate Oligonucleotides [0217]
[2′-O-(2-methoxyethyl)]—[2′-deoxy]—[-2′-O-(methoxy-ethyl)] chimeric phosphorothioate oligonucleotides were prepared as per the procedure above for the 2′-O-methyl chimeric oligonucleotide, with the substitution of 2′-O-(methoxyethyl) amidites for the 2′-O-methyl amidites. [0218]
[2′-O-(2-Methoxyethyl)Phosphodiester]—[2′-deoxy Phosphorothioate]—[2′-O-(2-Methoxyethyl) Phosphodiester] Chimeric Oligonucleotides [0219]
[2′-O-(2-methoxyethyl phosphodiester]—[2′-deoxy phosphorothioate]—[2′-O-(methoxyethyl) phosphodiester] chimeric oligonucleotides are prepared as per the above procedure for the 2′-O-methyl chimeric oligonucleotide with the substitution of 2′-O-(methoxyethyl) amidites for the 2′-O-methyl amidites, oxidization with iodine to generate the phosphodiester internucleotide linkages within the wing portions of the chimeric structures and sulfurization utilizing 3,H-1,2 benzodithiole-3-one 1,1 dioxide (Beaucage Reagent) to generate the phosphorothioate internucleotide linkages for the center gap. [0220]
Other chimeric oligonucleotides, chimeric oligonucleo-sides and mixed chimeric oligonucleotides/oligonucleosides are synthesized according to U.S. Pat. No. 5,623,065, herein incorporated by reference. [0221]

Example 6

Oligonucleotide Isolation [0222]
After cleavage from the controlled pore glass column (Applied Biosystems) and deblocking in concentrated ammonium hydroxide at 55° C. for 18 hours, the oligonucleotides or oligonucleosides are purified by precipitation twice out of 0.5 M NaCl with 2.5 volumes ethanol. Synthesized oligonucleotides were analyzed by polyacrylamide gel electrophoresis on denaturing gels and judged to be at least 85% full length material. The relative amounts of phosphorothioate and phosphodiester linkages obtained in synthesis were periodically checked by [0223] ³¹P nuclear magnetic resonance spectroscopy, and for some studies oligonucleotides were purified by HPLC, as described by Chiang et al., J. Biol. Chem. 1991, 266, 18162-18171. Results obtained with HPLC-purified material were similar to those obtained with non-HPLC purified material.

Example 7

Oligonucleotide Synthesis—96 Well Plate Format [0224]
Oligonucleotides were synthesized via solid phase P(III) phosphoramidite chemistry on an automated synthesizer capable of assembling 96 sequences simultaneously in a standard 96 well format. Phosphodiester internucleotide linkages were afforded by oxidation with aqueous iodine. Phosphorothioate internucleotide linkages were generated by sulfurization utilizing 3,H-1,2 benzodithiole-3-one 1,1 dioxide (Beaucage Reagent) in anhydrous acetonitrile. Standard base-protected beta-cyanoethyldiisopropyl phosphoramidites were purchased from commercial vendors (e.g. PE-Applied Biosystems, Foster City, Calif., or Pharmacia, Piscataway, N.J.). Non-standard nucleosides are synthesized as per known literature or patented methods. They are utilized as base protected beta-cyanoethyldiisopropyl phosphoramidites. [0225]
Oligonucleotides were cleaved from support and deprotected with concentrated NH[0226] ₄OH at elevated temperature (55-60° C.) for 12-16 hours and the released product then dried in vacuo. The dried product was then re-suspended in sterile water to afford a master plate from which all analytical and test plate samples are then diluted utilizing robotic pipettors.

Example 8

Oligonucleotide Analysis—96 Well Plate Format [0227]
The concentration of oligonucleotide in each well was assessed by dilution of samples and UV absorption spectroscopy. The full-length integrity of the individual products was evaluated by capillary electrophoresis (CE) in either the 96 well format (Beckman P/ACE™ MDQ) or, for individually prepared samples, on a commercial CE apparatus (e.g., Beckman P/ACE™ 5000, ABI 270). Base and backbone composition was confirmed by mass analysis of the compounds utilizing electrospray-mass spectroscopy. All assay test plates were diluted from the master plate using single and multi-channel robotic pipettors. Plates were judged to be acceptable if at least 85% of the compounds on the plate were at least 85% full length. [0228]

Example 9

Cell Culture and Oligonucleotide Treatment [0229]
The effect of antisense compounds on target nucleic acid expression can be tested in any of a variety of cell types provided that the target nucleic acid is present at measurable levels. This can be routinely determined using, for example, PCR or Northern blot analysis. The following 5 cell types are provided for illustrative purposes, but other cell types can be routinely used, provided that the target is expressed in the cell type chosen. This can be readily determined by methods routine in the art, for example Northern blot analysis, Ribonuclease protection assays, or RT-PCR. [0230]
T-24 Cells: [0231]
The human transitional cell bladder carcinoma cell line T-24 was obtained from the American Type Culture Collection (ATCC) (Manassas, Va.). T-24 cells were routinely cultured in complete McCoy's SA basal media (Invitrogen Corporation, Carlsbad, Calif.) supplemented with 10% fetal calf serum ((Invitrogen Corporation, Carlsbad, Calif.), penicillin 100 units per mL, and streptomycin 100 micrograms per mL (Invitrogen Corporation, Carlsbad, Calif.). Cells were routinely passaged by trypsinization and dilution when they reached 90% confluence. Cells were seeded into 96-well plates (Falcon-Primaria #3872) at a density of 7000 cells/well for use in RT-PCR analysis. [0232]
For Northern blotting or other analysis, cells may be seeded onto 100 mm or other standard tissue culture plates and treated similarly, using appropriate volumes of medium and oligonucleotide. [0233]
A549 Cells: [0234]
The human lung carcinoma cell line A549 was obtained from the American Type Culture Collection (ATCC) (Manassas, Va.). A549 cells were routinely cultured in DMEM basal media (Invitrogen Corporation, Carlsbad, Calif.) supplemented with 10% fetal calf serum (Invitrogen Corporation, Carlsbad, Calif.), penicillin 100 units per mL, and streptomycin 100 micrograms per mL (Invitrogen Corporation, Carlsbad, Calif.). Cells were routinely passaged by trypsinization and dilution when they reached 90% confluence. [0235]
NHDF Cells: [0236]
Human neonatal dermal fibroblast (NHDF) were obtained from the Clonetics Corporation (Walkersville, Md.). NHDFs were routinely maintained in Fibroblast Growth Medium (Clonetics Corporation, Walkersville, Md.) supplemented as recommended by the supplier. Cells were maintained for up to 10 passages as recommended by the supplier. [0237]
HEK Cells: [0238]
Human embryonic keratinocytes (HEK) were obtained from the Clonetics Corporation (Walkersville, Md.). HEKs were routinely maintained in Keratinocyte Growth Medium (Clonetics Corporation, Walkersville, Md.) formulated as recommended by the supplier. Cells were routinely maintained for up to 10 passages as recommended by the supplier. [0239]
MCF7: [0240]
The human breast carcinoma cell line MCF-7 was obtained from the American Type Culture Collection (Manassas, Va.). MCF-7 cells were routinely cultured in DMEM low glucose (Gibco/Life Technologies, Gaithersburg, Md.) supplemented with 10% fetal calf serum (Gibco/Life Technologies, Gaithersburg, Md.). Cells were routinely passaged by trypsinization and dilution when they reached 90% confluence. Cells were seeded into 96-well plates (Falcon-Primaria #3872) at a density of 7000 cells/well for use in RT-PCR analysis. [0241]
For Northern blotting or other analyses, cells may be seeded onto 100 mm or other standard tissue culture plates and treated similarly, using appropriate volumes of medium and oligonucleotide. [0242]
Treatment with Antisense Compounds: [0243]
When cells reached 70% confluency, they were treated with oligonucleotide. For cells grown in 96-well plates, wells were washed once with 100 μL OPTI-MEM™-1 reduced-serum medium (Invitrogen Corporation, Carlsbad, Calif.) and then treated with 130 μL of OPTI-MEM™-1 containing 3.75 μμg/mL LIPOFECTIN™ (Invitrogen Corporation, Carlsbad, Calif.) and the desired concentration of oligonucleotide. After 4-7 hours of treatment, the medium was replaced with fresh medium. Cells were harvested 16-24 hours after oligonucleotide treatment. [0244]
The concentration of oligonucleotide used varies from cell line to cell line. To determine the optimal oligonucleotide concentration for a particular cell line, the cells are treated with a positive control oligonucleotide at a range of concentrations. For human cells the positive control oligonucleotide is ISIS 13920, TCCGTCATCGCTCCTCAGGG, SEQ ID NO: 1, a 2′-O-methoxyethyl gapmer (2′-O-methoxyethyls shown in bold) with a phosphorothioate backbone which is targeted to human H-ras. For mouse or rat cells the positive control oligonucleotide is ISIS 15770, ATGCATTCTGCCCCCAAGGA, SEQ ID NO: 2, a 2′-O-methoxyethyl gapmer (2′-O-methoxyethyls shown in bold) with a phosphorothioate backbone which is targeted to both mouse and rat c-raf. The concentration of positive control oligonucleotide that results in 80% inhibition of c-Ha-ras (for ISIS 13920) or c-raf (for ISIS 15770) mRNA is then utilized as the screening concentration for new oligonucleotides in subsequent experiments for that cell line. If 80% inhibition is not achieved, the lowest concentration of positive control oligonucleotide that results in 60% inhibition of H-ras or c-raf mRNA is then utilized as the oligonucleotide screening concentration in subsequent experiments for that cell line. If 60% inhibition is not achieved, that particular cell line is deemed as unsuitable for oligonucleotide transfection experiments. [0245]

Example 10

Analysis of Oligonucleotide Inhibition of Estrogen Receptor Alpha Expression [0246]
Antisense modulation of estrogen receptor alpha expression can be assayed in a variety of ways known in the art. For example, estrogen receptor alpha mRNA levels can be quantitated by, e.g., Northern blot analysis, competitive polymerase chain reaction (PCR), or real-time PCR (RT-PCR). Real-time quantitative PCR is presently preferred. RNA analysis can be performed on total cellular RNA or poly(A)+ mRNA. The preferred method of RNA analysis of the present invention is the use of total cellular RNA as described in other examples herein. Methods of RNA isolation are taught in, for example, Ausubel, F. M. et al., [0247] Current Protocols in Molecular Biology, Volume 1, pp. 4.1.1-4.2.9 and 4.5.1-4.5.3, John Wiley & Sons, Inc., 1993. Northern blot analysis is routine in the art and is taught in, for example, Ausubel, F. M. et al., Current Protocols in Molecular Biology, Volume 1, pp. 4.2.1-4.2.9, John Wiley & Sons, Inc., 1996. Real-time quantitative (PCR) can be conveniently accomplished using the commercially available ABI PRISMTM 7700 Sequence Detection System, available from PE-Applied Biosystems, Foster City, Calif. and used according to manufacturer's instructions.
Protein levels of estrogen receptor alpha can be quantitated in a variety of ways well known in the art, such as immunoprecipitation, Western blot analysis (immunoblotting), ELISA or fluorescence-activated cell sorting (FACS). Antibodies directed to estrogen receptor alpha can be identified and obtained from a variety of sources, such as the MSRS catalog of antibodies (Aerie Corporation, Birmingham, Mich.), or can be prepared via conventional antibody generation methods. Methods for preparation of polyclonal antisera are taught in, for example, Ausubel, F. M. et al., [0248] Current Protocols in Molecular Biology, Volume 2, pp. 11.12.1-11.12.9, John Wiley & Sons, Inc., 1997. Preparation of monoclonal antibodies is taught in, for example, Ausubel, F. M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.4.1-11.11.5, John Wiley & Sons, Inc., 1997.
Immunoprecipitation methods are standard in the art and can be found at, for example, Ausubel, F. M. et al., [0249] Current Protocols in Molecular Biology, Volume 2, pp. 10.16.1-10.16.11, John Wiley & Sons, Inc., 1998. Western blot (immunoblot) analysis is standard in the art and can be found at, for example, Ausubel, F. M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 10.8.1-10.8.21, John Wiley & Sons, Inc., 1997. Enzyme-linked immunosorbent assays (ELISA) are standard in the art and can be found at, for example, Ausubel, F. M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.2.1-11.2.22, John Wiley & Sons, Inc., 1991.

Example 11

Poly(A)+mRNA Isolation [0250]
Poly(A)+MRNA was isolated according to Miura et al., [0251] Clin. Chem., 1996, 42, 1758-1764. Other methods for poly(A)+mRNA isolation are taught in, for example, Ausubel, F. M. et al., Current Protocols in Molecular Biology, Volume 1, pp. 4.5.1-4.5.3, John Wiley & Sons, Inc., 1993. Briefly, for cells grown on 96-well plates, growth medium was removed from the cells and each well was washed with 200 1L cold PBS. 60 μL lysis buffer (10 mM Tris-HC1, pH 7.6, 1 mM EDTA, 0.5 M NaCl, 0.5% NP-40, 20 mM vanadyl-ribonucleoside complex) was added to each well, the plate was gently agitated and then incubated at room temperature for five minutes. 55 μL of lysate was transferred to Oligo d(T) coated 96-well plates (AGCT Inc., Irvine Calif.). Plates were incubated for 60 minutes at room temperature, washed 3 times with 200 μL of wash buffer (10 mM Tris-HCl pH 7.6, 1 mM EDTA, 0.3 M NaCl). After the final wash, the plate was blotted on paper towels to remove excess wash buffer and then air-dried for 5 minutes. 60 μL of elution buffer (5 mM Tris-HCl pH 7.6), preheated to 70° C. was added to each well, the plate was incubated on a 90° C. hot plate for 5 minutes, and the eluate was then transferred to a fresh 96-well plate.
Cells grown on 100 mm or other standard plates may be treated similarly, using appropriate volumes of all solutions. [0252]

Example 12

Total RNA Isolation [0253]
Total RNA was isolated using an RNEASY [0254] ₉₆™ kit and buffers purchased from Qiagen Inc. (Valencia, Calif.) following the manufacturer's recommended procedures. Briefly, for cells grown on 96-well plates, growth medium was removed from the cells and each well was washed with 200 μL cold PBS. 150 μL Buffer RLT was added to each well and the plate vigorously agitated for 20 seconds. 150 μL of 70% ethanol was then added to each well and the contents mixed by pipetting three times up and down. The samples were then transferred to the RNEASY 96™ well plate attached to a QIAVAC™ manifold fitted with a waste collection tray and attached to a vacuum source. Vacuum was applied for 1 minute. 500 μL of Buffer RW1 was added to each well of the RNEASY ₉₆TM plate and incubated for 15 minutes and the vacuum was again applied for 1 minute. An additional 500 μL of Buffer RW1 was added to each well of the RNEASY 96™ plate and the vacuum was applied for 2 minutes. 1 mL of Buffer RPE was then added to each well of the RNEASY ₉₆™ plate and the vacuum applied for a period of 90 seconds. The Buffer RPE wash was then repeated and the vacuum was applied for an additional 3 minutes. The plate was then removed from the QIAVAC™ manifold and blotted dry on paper towels. The plate was then re-attached to the QIAVAC™ manifold fitted with a collection tube rack containing 1.2 mL collection tubes. RNA was then eluted by pipetting 170 μL water into each well, incubating 1 minute, and then applying the vacuum for 3 minutes.
The repetitive pipetting and elution steps may be automated using a QIAGEN Bio-Robot 9604 (Qiagen, Inc., Valencia Calif.). Essentially, after lysing of the cells on the culture plate, the plate is transferred to the robot deck where the pipetting, DNase treatment and elution steps are carried out. [0255]

Example 13

Real-Time Quantitative PCR Analysis of Estrogen Receptor Alpha mRNA Levels [0256]
Quantitation of estrogen receptor alpha MRNA levels was determined by real-time quantitative PCR using the ABI PRISM™ 7700 Sequence Detection System (PE-Applied Biosystems, Foster City, Calif.) according to manufacturer's instructions. This is a closed-tube, non-gel-based, fluorescence detection system which allows high-throughput quantitation of polymerase chain reaction (PCR) products in real-time. As opposed to standard PCR, in which amplification products are quantitated after the PCR is completed, products in real-time quantitative PCR are quantitated as they accumulate. This is accomplished by including in the PCR reaction an oligonucleotide probe that anneals specifically between the forward and reverse PCR primers, and contains two fluorescent dyes. A reporter dye (e.g., FAM, obtained from either Operon Technologies Inc., Alameda, Calif. or Integrated DNA Technologies Inc., Coralville, Iowa) is attached to the 5′ end of the probe and a quencher dye (e.g., TAMPA, obtained from either Operon Technologies Inc., Alameda, Calif. or Integrated DNA Technologies Inc., Coralville, IA) is attached to the 3′ end of the probe. When the probe and dyes are intact, reporter dye emission is quenched by the proximity of the 3′ quencher dye. During amplification, annealing of the probe to the target sequence creates a substrate that can be cleaved by the 5′-exonuclease activity of Taq polymerase. During the extension phase of the PCR amplification cycle, cleavage of the probe by Taq polymerase releases the reporter dye from the remainder of the probe (and hence from the quencher moiety) and a sequence-specific fluorescent signal is generated. With each cycle, additional reporter dye molecules are cleaved from their respective probes, and the fluorescence intensity is monitored at regular intervals by laser optics built into the ABI PRISMT™ 7700 Sequence Detection System. In each assay, a series of parallel reactions containing serial dilutions of mRNA from untreated control samples generates a standard curve that is used to quantitate the percent inhibition after antisense oligonucleotide treatment of test samples. [0257]
Prior to quantitative PCR analysis, primer-probe sets specific to the target gene being measured are evaluated for their ability to be “multiplexed” with a GAPDH amplification reaction. In multiplexing, both the target gene and the internal standard gene GAPDH are amplified concurrently in a single sample. In this analysis, mRNA isolated from untreated cells is serially diluted. Each dilution is amplified in the presence of primer-probe sets specific for GAPDH only, target gene only (“single-plexing”), or both (multiplexing). Following PCR amplification, standard curves of GAPDH and target mRNA signal as a function of dilution are generated from both the single-plexed and multiplexed samples. If both the slope and correlation coefficient of the GAPDH and target signals generated from the multiplexed samples fall within 10′ of their corresponding values generated from the single-plexed samples, the primer-probe set specific for that target is deemed multiplexable. Other methods of PCR are also known in the art. [0258]
PCR reagents were obtained from Invitrogen, Carlsbad, Calif. RT-PCR reactions were carried out by adding 20 μL PCR cocktail (2.5× PCR buffer (—MgCl2), 6.6 mM MgCl2, 375 μM each of DATP, dCTP, dCTP and dGTP, 375 nM each of forward primer and reverse primer, 125 nM of probe, 4 Units RNAse inhibitor, 1.25 Units PLATINUM™ Taq, 5 Units MuLV reverse transcriptase, and 2.5× ROX dye) to 96 well plates containing 30 μL total RNA solution. The RT reaction was carried out by incubation for 30 minutes at 48° C. Following a 10 minute incubation at 95° C. to activate the PLATINUM™ Taq, 40 cycles of a two-step PCR protocol were carried out: 95° C. for 15 seconds (denaturation) followed by 60° C. for 1.5 minutes (annealing/extension). [0259]
Gene target quantities obtained by real time RT-PCR are normalized using either the expression level of GAPDH, a gene whose expression is constant, or by quantifying total RNA using RiboGreen™ (Molecular Probes, Inc. Eugene, Oreg.). GAPDH expression is quantified by real time RT-PCR, by being run simultaneously with the target, multiplexing, or separately. Total RNA is quantified using RiboGreen™ RNA quantification reagent from Molecular Probes. Methods of RNA quantification by RiboGreen™ are taught in Jones, L. J., et al, Analytical Biochemistry, 1998, 265, 368-374. [0260]
In this assay, 170 μL of RiboGreen™ working reagent (RiboGreen™ reagent diluted 1:350 in 10 mM Tris-HCl, 1 mM EDTA, pH 7.5) is pipetted into a 96-well plate containing 30 μL purified, cellular RNA. The plate is read in a CytoFluor 4000 (PE Applied Biosystems) with excitation at 480 nm and emission at 520 nm. [0261]
Probes and primers to human estrogen receptor alpha were designed to hybridize to a human estrogen receptor alpha sequence, using published sequence information (GenBank accession number NM[0262] _—000125.1, incorporated herein as SEQ ID NO:3). For human estrogen receptor alpha the PCR primers were:
forward primer: GTAGAGGGCATGGTGGAGATCTT (SEQ ID NO: 4) [0263]
reverse primer: CAAACTCCTCTCCCTGCAGATT (SEQ ID NO: 5) and the PCR probe was: FAM-TGCTGGCTACATCATCTCGGTTCCG-TAMRA (SEQ ID NO: 6) where FAM (PE-Applied Biosystems, Foster City, Calif.) is the fluorescent reporter dye) and TAMRA (PE-Applied Biosystems, Foster City, Calif.) is the quencher dye. For human GAPDH the PCR primers were: [0264]
forward primer: GAAGGTGAAGGTCGGAGTC(SEQ ID NO:7) [0265]
reverse primer: GAAGATGGTGATGGGATTTC (SEQ ID NO:8) and the PCR probe was: 5′ JOE-CAAGCTTCCCGTTCTCAGCC-TAMRA 3′ (SEQ ID NO: 9) where JOE (PE-Applied Biosystems, Foster City, Calif.) is the fluorescent reporter dye) and TAMPA (PE-Applied Biosystems, Foster City, Calif.) is the quencher dye. [0266]

Example 14

Northern Blot Analysis of Estrogen Receptor Alpha mRNA Levels [0267]
Eighteen hours after antisense treatment, cell monolayers were washed twice with cold PBS and lysed in 1 mL RNAZOL™ (TEL-TEST “B” Inc., Friendswood, Tex.). Total RNA was prepared following manufacturer's recommended protocols. Twenty micrograms of total RNA was fractionated by electrophoresis through 1.2% agarose gels containing 1.1% formaldehyde using a MOPS buffer system (AMRESCO, Inc. Solon, Ohio). RNA was transferred from the gel to HYBONDTM-N+nylon membranes (Amersham Pharmacia Biotech, Piscataway, N.J.) by overnight capillary transfer using a Northern/Southern Transfer buffer system (TEL-TEST “B” Inc., Friendswood, Tex.). RNA transfer was confirmed by UV visualization. Membranes were fixed by UV cross-linking using a STRATALINKERTM UV Crosslinker 2400 (Stratagene, Inc, La Jolla, Calif.) and then probed using QUICKHYB™ hybridization solution (Stratagene, La Jolla, Calif.) using manufacturer's recommendations for stringent conditions. [0268]
To detect human estrogen receptor alpha, a human estrogen receptor alpha specific probe was prepared by PCR using the forward primer GTAGAGGGCATGGTGGAGATCTT (SEQ ID NO: 4) and the reverse primer CAAACTCCTCTCCCTGCAGATT (SEQ ID NO: 5). To normalize for variations in loading and transfer efficiency membranes were stripped and probed for human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RNA (Clontech, Palo Alto, Calif.). [0269]
Hybridized membranes were visualized and quantitated using a PHOSPHORIMAGER™ and IMAGEQUANT™ Software V3.3 (Molecular Dynamics, Sunnyvale, Calif.). Data was normalized to GAPDH levels in untreated controls. [0270]

Example 15

Antisense Inhibition of Human Estrogen Receptor Alpha Expression by Chimeric Phosphorothioate Oligonucleotides Having 2′-MOE Wings and a Deoxy Gap [0271]

In accordance with the present invention, a series of oligonucleotides were designed to target different regions of the human estrogen receptor alpha RNA, using published sequences (GenBank accession number NM _—000125.1, representing the main mRNA of estrogen receptor alpha, incorporated herein as SEQ ID NO: 3; a concatenated sequence of exons 1A, 2, 1B, 1C, and 4-12 from GenBank accession number NT_—007587 (a sequence segment of chromosome 6), incorporated herein as SEQ ID NO: 10; residues 491001-883000 of GenBank accession number NT_—007587.3, representing a partial genomic sequence of estrogen receptor alpha, incorporated herein as SEQ ID NO: 11; GenBank accession number AF258449.1, representing the estrogen receptor alpha variant herein designated ESR-alpha-V, incorporated herein as SEQ ID NO: 12; GenBank accession number AF258451.1, representing the estrogen receptor alpha variant herein designated ESR-alpha-VI, incorporated herein as SEQ ID NO: 13; GenBank accession number AI630824.1, representing the estrogen receptor alpha variant herein designated ESR-alpha-VIII, incorporated herein as SEQ ID NO: 14; GenBank accession number M69297.1, representing the estrogen receptor alpha variant herein designated ESR-alpha-IX, incorporated herein as SEQ ID NO: 15; GenBank accession number U68067.1, representing the estrogen receptor alpha variant herein designated ESR-alpha-IV, incorporated herein as SEQ ID NO: 16; GenBank accession number U68068.1, representing the estrogen receptor alpha variant herein designated ESR-alpha-III, incorporated herein as SEQ ID NO: 17; and GenBank accession number X73067.1, representing the estrogen receptor alpha variant herein designated ESR-alpha-II, incorporated herein as SEQ ID NO: 18). The oligonucleotides are shown in Table 1. “Target site” indicates the first (5′-most) nucleotide number on the particular target sequence to which the oligonucleotide binds. All compounds in Table 1 are chimeric oligonucleotides (“gapmers”) 20 nucleotides in length, composed of a central “gap” region consisting of ten 2′-deoxynucleotides, which is flanked on both sides (5′ and 3′ directions) by five-nucleotide “wings”. The wings are composed of 2′-methoxyethyl (2′-MOE)nucleotides. The internucleoside (backbone) linkages are phosphorothioate (P=S) throughout the oligonucleotide. All cytidine residues are 5-methylcytidines. The compounds were analyzed for their effect on human estrogen receptor alpha mRNA levels by quantitative real-time PCR as described in other examples herein. Data are averages from two experiments. If present, “N.D.” indicates “no data”.

TABLE 1


Inhibition of human estrogen receptor alpha mRNA levels by
chimeric phosphorothioate oligonucleotides having 2′-MOE
wings and a deoxy gap

		TARGET
		SEQ ID	TARGET			SEQ ID
ISIS #	REGION	NO	SITE	SEQUENCE	% INHIB	NO

192243	Coding	3	802	gaatttggcctgtagaatgc	46	19
192244	Coding	3	993	cgttatgtccttgaatactt	55	20
192245	5′UTR	10	9	aaaggagcatggacctttcg	34	21
192246	5′UTR	10	196	tcagtgatggttcaaagttc	0	22
192247	5′UTR	10	760	tcatggtcatggtccgtggc	48	23
192248	5′UTR	10	818	agctcgttcccttggatctg	55	24
192249	5′UTR	10	823	gctccagctcgttcccttgg	58	25
192250	5′UTR	10	908	ttgtacacggcgggcttgct	56	26
192251	5′UTR	10	1080	tagcatcagcgggctcggag	71	27
192252	5′UTR	10	1139	tagggcacctgctggccgtg	75	28
192253	5′UTR	10	1148	tccaggtagtagggcacctg	67	29
192254	5′UTR	10	1153	cgttctccaggtagtagggc	57	30
192255	5′UTR	10	1158	gggctcgttctccaggtagt	78	31
192256	Exon:	10	1454	tctcagcttgccaagtaaca	49	32
	Exon
	Junction
192257	Exon:	10	1482	tgaatttggcgagtaacatc	0	33
	Exon
	Junction
192258	5′UTR	10	1571	tagcgagtctccttggcaga	64	34
192259	5′UTR	10	1576	cacagtagcgagtctccttg	62	35
192260	5′UTR	10	2149	cagtctgatggtagtttctt	39	36
192263	5′UTR	10	2160	ggttgcctgttcagtctgat	76	37
192264	5′UTR	10	2279	ttcacccacttgttgatggg	13	38
192265	Start	10	2293	gtctgttcatatccttcacc	71	39
	Codon
192266	Coding	10	2407	ctggtgtgagatggtatctc	63	40
192267	Coding	10	2435	cctgactttctaatgatcac	29	41
192268	Coding	10	2504	agtttacagtcccaccaaca	47	42
192269	Coding	10	2540	aggaatcgccacactgtctt	77	43
192270	Coding	10	2635	atgtgtctttatagcagcat	78	44
192271	3′UTR	10	3023	atgttggtgtgctgcaccca	53	45
192272	3′UTR	10	3073	agggtacatgtgcacaatgt	40	46
192273	3′UTR	10	3326	ttggcagctctcatgtctcc	66	47
192274	3′UTR	10	3331	aaaggttggcagctctcatg	56	48
192275	3′UTR	10	3338	cttggccaaaggttggcagc	49	49
192276	3′UTR	10	3413	aaggcactgaccatctggtc	72	50
192277	3′UTR	10	3418	ccaacaaggcactgaccatc	38	51
192278	3′UTR	10	3423	agcatccaacaaggcactga	43	52
192279	3′UTR	10	3518	agctccctgtctgccaggtt	75	53
192280	3′UTR	10	3523	gaaccagctccctgtctgcc	84	54
192281	Exon:	10	3560	tccacaaagcgcaccctctt	11	55
	Exon
	Junction
192282	3′UTR	10	3587	aggtggacctgatcatggag	41	56
192283	3′UTR	10	3632	cagacgagaccaatcatcag	27	57
192284	3′UTR	10	3680	agcaagttaggagcaaacag	14	58
192285	3′UTR	10	3685	ccaagagcaagttaggagca	31	59
192286	Exon:	10	3690	cctgtccaagagcaagttag	52	60
	Exon
	Junction
192287	Exon:	10	3803	gatttgaggcacacaaactc	19	61
	Exon
	Junction
192288	Exon:	10	3830	tacactccagaattaagcaa	0	62
	Exon
	Junction
192289	3′UTR	10	3835	atgtgtacactccagaatta	7	63
192290	3′UTR	10	3870	cttctcttccagagacttca	13	64
192291	3′UTR	10	3875	tggtccttctcttccagaga	28	65
192292	3′UTR	10	3896	ttgtccaggactcggtggat	22	66
192293	3′UTR	10	3905	tctgtgatcttgtccaggac	13	67
192294	3′UTR	10	3910	aagtgtctgtgatcttgtcc	28	68
192295	3′UTR	10	3915	gatcaaagtgtctgtgatct	0	69
192296	3′UTR	10	3920	aggtggatcaaagtgtctgt	0	70
192297	3′UTR	10	3925	ccatcaggtggatcaaagtg	33	71
192298	Exon:	10	4017	gcctttgttactcatgtgcc	14	72
	Exon
	Junction
192299	3′UTR	10	4249	ggagctctcagaccgtggca	26	73
192300	3′UTR	10	4778	ctttaaggtgtaccactttc	46	74
192301	3′UTR	10	5464	gaagaagagctggactaccc	23	75
192302	3′UTR	10	6143	caacaaaagaattatgttct	2	76
192303	3′UTR	10	7320	agcctctcataattgctgca	54	77
192304	3′UTR	10	8541	attctttatttgaacatcaa	31	78
192305	Coding	15	873	ttggaagttcttgaatactt	0	79
192306	Exon:	14	250	agcaccattctgtagaatgc	12	80
	Exon
	Junction
192307	3′UTR	13	412	acaaagcctgtccaagagca	35	81
192308	Stop	12	674	cgttatgtcctgtagaatgc	0	82
	Codon
192309	3′UTR	12	791	ccctggttccacctttcatc	11	83
192310	Exon:	16	181	gcgggccactttacttgtcg	20	84
	Exon
	Junction
192311	Exon:	17	75	ttcttcttcttgaagagaag	5	85
	Exon
	Junction
192312	Exon:	17	206	gcgggccacctcagtgatgg	0	86
	Exon
	Junction
192313	Exon:	18	105	ccacaaagccacctttcatc	0	87
	Exon
	Junction
192314	Exon:	18	244	ccctggttcctgtccaagag	59	88
	Exon
	Junction
192315	Exon 1A	11	1391	agtacctacttgaagagaag	12	89
192316	Intron	11	12000	aagtgctgagattacagatg	34	90
	1A
192317	Exon 1C	11	119091	cgcgggtacctgtagaatgc	44	91
192318	Exon:	11	151119	cactattaccttgaatactt	13	92
	Intron
	Junction
192319	Exon:	11	299238	gtcacttacctgtccaagag	22	93
	Intron
	Junction
192320	Intron	11	348568	tcaactcaccagaattaagc	0	94
	10
192321	Intron	11	348600	catttcatccagcattgagt	52	95
	10
192322	Intron:	11	386175	cctttgttactgtaggtggg	13	96
	Exon
	Junction

As shown in Table 1, SEQ ID NOs 19, 20, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 37, 39, 40, 42, 43, 44, 45, 46, 47, 48, 49, 50, 52, 53, 54, 56, 60, 74, 77, 88, 91 and 95 demonstrated at least 40% inhibition of human estrogen receptor alpha expression in this assay and are therefore preferred. The target sites to which these preferred sequences are complementary are herein referred to as “active sites” and are therefore preferred sites for targeting by compounds of the present invention. [0273]

Example 16

Western Blot Analysis of Estrogen Receptor Alpha Protein Levels [0274]
Western blot analysis (immunoblot analysis) is carried out using standard methods. Cells are harvested 16-20 h after oligonucleotide treatment, washed once with PBS, suspended in Laemmli buffer (100 ul/well), boiled for 5 minutes and loaded on a 16% SDS-PAGE gel. Gels are run for 1.5 hours at 150 V, and transferred to membrane for western blotting. Appropriate primary antibody directed to estrogen receptor alpha is used, with a radiolabelled or fluorescently labeled secondary antibody directed against the primary antibody species. Bands are visualized using a PHOSPHORIMAGER™ (Molecular Dynamics, Sunnyvale Calif.). [0275]

Example 17

Targeting of Individual Oligonucleotides to Specific Variants of Estrogen Receptor Alpha [0276]

It is advantageous to selectively inhibit the expression of one or more variants of estrogen receptor alpha. Consequently, in one embodiment of the present invention are oligonucleotides that selectively target, hybridize to, and specifically inhibit one or more, but fewer than all of the variants of estrogen receptor alpha. A summary of the target sites of the variants is shown in Table 2 and includes Genbank accession number NM _—00125.1, representing estrogen receptor alpha main mRNA (ESR-alpha), incorporated herein as SEQ ID NO: 3; Genbank accession number AF258449.1, representing ESR-alpha-V, incorporated herein as SEQ ID NO: 12; Genbank accession number AF258451.1, representing ESR-alpha-VI, incorporated herein as SEQ ID NO: 13; Genbank accession number AI630824.1, representing ESR-alpha-VIII, incorporated herein as SEQ ID NO: 14; Genbank accession number M69297.1, representing ESR-alpha-IX, incorporated herein as SEQ ID NO: 15; Genbank accession number U68067.1, representing ESR-alpha-IV, incorporated herein as SEQ ID NO: 16; Genbank accession number U68067.1, representing ESR-alpha-III, incorporated herein as SEQ ID NO: 17; Genbank accession number X73067.1, representing ESR-alpha-II, incorporated herein as SEQ ID NO: 18; Genbank accession number S80316.1, representing the estrogen receptor variant herein designated ESR-alpha-VII, incorporated herein as SEQ ID NO: 97; and Genbank accession number AF172068.1, representing the fusion transcript of estrogen receptor alpha with fatty acid synthase (ESR-alpha/FASN), incorporated herein as SEQ ID NO: 98.

TABLE 2


Targeting of individual oligonucleotides to specific variants
of estrogen receptor alpha and the fusion transcript of
estrogen receptor alpha with fatty acid synthase

	OLIGO SEQ	TARGET		VARIANT SEQ
ISIS #	ID NO.	SITE	VARIANT	ID NO.

192243	19	802	ESR-alpha	3
192243	19	682	ESR-alpha-IX	15
192244	20	993	ESR-alpha	3
192245	21	9	ESR-alpha-III	17
192246	22	196	ESR-alpha-III	17
192247	23	351	ESR-alpha	3
192247	23	277	ESR-alpha-III	17
192247	23	252	ESR-alpha-IV	16
192247	23	223	ESR-alpha-V	12
192247	23	223	ESR-alpha-VI	13
192247	23	231	ESR-alpha-IX	15
192248	24	409	ESR-alpha	3
192248	24	335	ESR-alpha-III	17
192248	24	310	ESR-alpha-IV	16
192248	24	281	ESR-alpha-V	12
192248	24	281	ESR-alpha-VI	13
192248	24	289	ESR-alpha-IX	15
192249	25	414	ESR-alpha	3
192249	25	286	ESR-alpha-V	12
192249	25	286	ESR-alpha-VI	13
192249	25	294	ESR-alpha-IX	15
192250	26	499	ESR-alpha	3
192250	26	371	ESR-alpha-V	12
192250	26	379	ESR-alpha-IX	15
192251	27	671	ESR-alpha	3
192251	27	543	ESR-alpha-V	12
192251	27	119	ESR-alpha-VIII	14
192251	27	551	ESR-alpha-IX	15
192252	28	730	ESR-alpha	3
192252	28	602	ESR-alpha-V	12
192252	28	178	ESR-alpha-VIII	14
192252	28	610	ESR-alpha-IX	15
192253	29	739	ESR-alpha	3
192253	29	611	ESR-alpha-V	12
192253	29	187	ESR-alpha-VIII	14
192253	29	619	ESR-alpha-IX	15
192254	30	744	ESR-alpha	3
192254	30	616	ESR-alpha-V	12
192254	30	192	ESR-alpha-VIII	14
192254	30	624	ESR-alpha-IX	15
192255	31	749	ESR-alpha	3
192255	31	621	ESR-alpha-V	12
192255	31	197	ESR-alpha-VIII	14
192255	31	629	ESR-alpha-IX	15
192256	32	493	ESR-alpha-VIII	14
192258	34	892	ESR-alpha	3
192258	34	772	ESR-alpha-IX	15
192259	35	897	ESR-alpha	3
192259	35	777	ESR-alpha-IX	15
192260	36	1346	ESR-alpha-IX	15
192263	37	1357	ESR-alpha-IX	15
192264	38	1476	ESR-alpha-IX	15
192265	39	1490	ESR-alpha-IX	15
192266	40	1604	ESR-alpha-IX	15
192267	41	1632	ESR-alpha-IX	15
192268	42	1701	ESR-alpha-IX	15
192269	43	1737	ESR-alpha-IX	15
192270	44	1832	ESR-alpha-IX	15
192271	45	2218	ESR-alpha-IX	15
192272	46	2268	ESR-alpha-IX	15
192273	47	1210	ESR-alpha	3
192274	48	1215	ESR-alpha	3
192275	49	1222	ESR-alpha	3
192276	50	1297	ESR-alpha	3
192276	50	367	ESR-alpha/FASN	98
192277	51	1302	ESR-alpha	3
192277	51	372	ESR-alpha/FASN	98
192278	52	1307	ESR-alpha	3
192278	52	377	ESR-alpha/FASN	98
192279	53	1402	ESR-alpha	3
192279	53	472	ESR-alpha/FASN	98
192280	54	1407	ESR-alpha	3
192280	54	477	ESR-alpha/FASN	98
192282	56	1474	ESR-alpha	3
192282	56	133	ESR-alpha-II	18
192282	56	442	ESR-alpha-VI	13
192282	56	544	ESR-alpha/FASN	98
192283	57	1519	ESR-alpha	3
192283	57	178	ESR-alpha-II	18
192283	57	348	ESR-alpha-VI	13
192283	57	487	ESR-alpha-VI	13
192283	57	589	ESR-alpha/FASN	98
192284	58	1567	ESR-alpha	3
192284	58	226	ESR-alpha-II	18
192284	58	396	ESR-alpha-VI	13
192284	58	535	ESR-alpha-VI	13
192284	58	637	ESR-alpha/FASN	98
192285	59	1572	ESR-alpha	3
192285	59	231	ESR-alpha-II	18
192285	59	401	ESR-alpha-VI	13
192285	59	540	ESR-alpha-VI	13
192285	59	642	ESR-alpha/FASN	98
192286	60	1577	ESR-alpha	3
192286	60	236	ESR-alpha-II	18
192286	60	406	ESR-alpha-VI	13
192286	60	545	ESR-alpha-VI	13
192286	60	647	ESR-alpha/FASN	98
192287	61	1690	ESR-alpha	3
192287	61	896	ESR-alpha-V	12
192287	61	658	ESR-alpha-VI	13
192287	61	760	ESR-alpha/FASN	98
192288	62	1717	ESR-alpha	3
192288	62	923	ESR-alpha-V	12
192288	62	685	ESR-alpha-VI	13
192288	62	787	ESR-alpha/FASN	98
192289	63	1722	ESR-alpha	3
192289	63	928	ESR-alpha-V	12
192289	63	690	ESR-alpha-VI	13
192289	63	792	ESR-alpha/FASN	98
192290	64	1757	ESR-alpha	3
192290	64	963	ESR-alpha-V	12
192290	64	725	ESR-alpha-VI	13
192290	64	827	ESR-alpha/FASN	98
192291	65	1762	ESR-alpha	3
192291	65	968	ESR-alpha-V	12
192291	65	730	ESR-alpha-VI	13
192291	65	832	ESR-alpha/FASN	98
192292	66	1783	ESR-alpha	3
192292	66	989	ESR-alpha-V	12
192292	66	751	ESR-alpha-VI	13
192292	66	853	ESR-alpha/FASN	98
192293	67	1792	ESR-alpha	3
192293	67	998	ESR-alpha-V	12
192293	67	760	ESR-alpha-VI	13
192293	67	862	ESR-alpha/FASN	98
192294	68	1797	ESR-alpha	3
192294	68	1003	ESR-alpha-V	12
192294	68	765	ESR-alpha-VI	13
192294	68	867	ESR-alpha/FASN	98
192295	69	1802	ESR-alpha	3
192295	69	1008	ESR-alpha-V	12
192295	69	770	ESR-alpha-VI	13
192295	69	872	ESR-alpha/FASN	98
192296	70	1807	ESR-alpha	3
192296	70	1013	ESR-alpha-V	12
192296	70	775	ESR-alpha-VI	13
192296	70	877	ESR-alpha/FASN	98
192297	71	1812	ESR-alpha	3
192297	71	1018	ESR-alpha-V	12
192297	71	780	ESR-alpha-VI	13
192297	71	882	ESR-alpha/FASN	98
192298	72	1904	ESR-alpha	3
192298	72	1110	ESR-alpha-V	12
192298	72	872	ESR-alpha-VI	13
192298	72	123	ESR-alpha-VII	97
192298	72	974	ESR-alpha/FASN	98
192300	74	2665	ESR-alpha	3
192302	76	4026	ESR-alpha	3
192303	77	5203	ESR-alpha	3
192304	78	6425	ESR-alpha	3
192305	79	873	ESR-alpha-IX	15
192306	80	250	ESR-alpha-VIII	14
192307	81	412	ESR-alpha-VI	13
192308	82	674	ESR-alpha-V	12
192309	83	791	ESR-alpha-V	12
192310	84	181	ESR-alpha-IV	16
192311	85	75	ESR-alpha-III	17
192312	86	206	ESR-alpha-III	17
192313	87	105	ESR-alpha-II	18
192314	88	1585	ESR-alpha	3
192314	88	244	ESR-alpha-II	18
192314	88	553	ESR-alpha-VI	13
192314	88	655	ESR-alpha/FASN	98

[0278]
1 98 1 20 DNA Artificial Sequence Antisense Oligonucleotide 1 tccgtcatcg ctcctcaggg 20 2 20 DNA Artificial Sequence Antisense Oligonucleotide 2 atgcattctg cccccaagga 20 3 6450 DNA Homo sapiens CDS (361)...(2148) 3 gagttgtgcc tggagtgatg tttaagccaa tgtcagggca aggcaacagt ccctggccgt 60 cctccagcac ctttgtaatg catatgagct cgggagacca gtacttaaag ttggaggccc 120 gggagcccag gagctggcgg agggcgttcg tcctgggagc tgcacttgct ccgtcgggtc 180 gccggcttca ccggaccgca ggctcccggg gcagggccgg ggccagagct cgcgtgtcgg 240 cgggacatgc gctgcgtcgc ctctaacctc gggctgtgct ctttttccag gtggcccgcc 300 ggtttctgag ccttctgccc tgcggggaca cggtctgcac cctgcccgcg gccacggacc 360 atg acc atg acc ctc cac acc aaa gca tct ggg atg gcc cta ctg cat 408 Met Thr Met Thr Leu His Thr Lys Ala Ser Gly Met Ala Leu Leu His 1 5 10 15 cag atc caa ggg aac gag ctg gag ccc ctg aac cgt ccg cag ctc aag 456 Gln Ile Gln Gly Asn Glu Leu Glu Pro Leu Asn Arg Pro Gln Leu Lys 20 25 30 atc ccc ctg gag cgg ccc ctg ggc gag gtg tac ctg gac agc agc aag 504 Ile Pro Leu Glu Arg Pro Leu Gly Glu Val Tyr Leu Asp Ser Ser Lys 35 40 45 ccc gcc gtg tac aac tac ccc gag ggc gcc gcc tac gag ttc aac gcc 552 Pro Ala Val Tyr Asn Tyr Pro Glu Gly Ala Ala Tyr Glu Phe Asn Ala 50 55 60 gcg gcc gcc gcc aac gcg cag gtc tac ggt cag acc ggc ctc ccc tac 600 Ala Ala Ala Ala Asn Ala Gln Val Tyr Gly Gln Thr Gly Leu Pro Tyr 65 70 75 80 ggc ccc ggg tct gag gct gcg gcg ttc ggc tcc aac ggc ctg ggg ggt 648 Gly Pro Gly Ser Glu Ala Ala Ala Phe Gly Ser Asn Gly Leu Gly Gly 85 90 95 ttc ccc cca ctc aac agc gtg tct ccg agc ccg ctg atg cta ctg cac 696 Phe Pro Pro Leu Asn Ser Val Ser Pro Ser Pro Leu Met Leu Leu His 100 105 110 ccg ccg ccg cag ctg tcg cct ttc ctg cag ccc cac ggc cag cag gtg 744 Pro Pro Pro Gln Leu Ser Pro Phe Leu Gln Pro His Gly Gln Gln Val 115 120 125 ccc tac tac ctg gag aac gag ccc agc ggc tac acg gtg cgc gag gcc 792 Pro Tyr Tyr Leu Glu Asn Glu Pro Ser Gly Tyr Thr Val Arg Glu Ala 130 135 140 ggc ccg ccg gca ttc tac agg cca aat tca gat aat cga cgc cag ggt 840 Gly Pro Pro Ala Phe Tyr Arg Pro Asn Ser Asp Asn Arg Arg Gln Gly 145 150 155 160 ggc aga gaa aga ttg gcc agt acc aat gac aag gga agt atg gct atg 888 Gly Arg Glu Arg Leu Ala Ser Thr Asn Asp Lys Gly Ser Met Ala Met 165 170 175 gaa tct gcc aag gag act cgc tac tgt gca gtg tgc aat gac tat gct 936 Glu Ser Ala Lys Glu Thr Arg Tyr Cys Ala Val Cys Asn Asp Tyr Ala 180 185 190 tca ggc tac cat tat gga gtc tgg tcc tgt gag ggc tgc aag gcc ttc 984 Ser Gly Tyr His Tyr Gly Val Trp Ser Cys Glu Gly Cys Lys Ala Phe 195 200 205 ttc aag aga agt att caa gga cat aac gac tat atg tgt cca gcc acc 1032 Phe Lys Arg Ser Ile Gln Gly His Asn Asp Tyr Met Cys Pro Ala Thr 210 215 220 aac cag tgc acc att gat aaa aac agg agg aag agc tgc cag gcc tgc 1080 Asn Gln Cys Thr Ile Asp Lys Asn Arg Arg Lys Ser Cys Gln Ala Cys 225 230 235 240 cgg ctc cgc aaa tgc tac gaa gtg gga atg atg aaa ggt ggg ata cga 1128 Arg Leu Arg Lys Cys Tyr Glu Val Gly Met Met Lys Gly Gly Ile Arg 245 250 255 aaa gac cga aga gga ggg aga atg ttg aaa cac aag cgc cag aga gat 1176 Lys Asp Arg Arg Gly Gly Arg Met Leu Lys His Lys Arg Gln Arg Asp 260 265 270 gat ggg gag ggc agg ggt gaa gtg ggg tct gct gga gac atg aga gct 1224 Asp Gly Glu Gly Arg Gly Glu Val Gly Ser Ala Gly Asp Met Arg Ala 275 280 285 gcc aac ctt tgg cca agc ccg ctc atg atc aaa cgc tct aag aag aac 1272 Ala Asn Leu Trp Pro Ser Pro Leu Met Ile Lys Arg Ser Lys Lys Asn 290 295 300 agc ctg gcc ttg tcc ctg acg gcc gac cag atg gtc agt gcc ttg ttg 1320 Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met Val Ser Ala Leu Leu 305 310 315 320 gat gct gag ccc ccc ata ctc tat tcc gag tat gat cct acc aga ccc 1368 Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr Asp Pro Thr Arg Pro 325 330 335 ttc agt gaa gct tcg atg atg ggc tta ctg acc aac ctg gca gac agg 1416 Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr Asn Leu Ala Asp Arg 340 345 350 gag ctg gtt cac atg atc aac tgg gcg aag agg gtg cca ggc ttt gtg 1464 Glu Leu Val His Met Ile Asn Trp Ala Lys Arg Val Pro Gly Phe Val 355 360 365 gat ttg acc ctc cat gat cag gtc cac ctt cta gaa tgt gcc tgg cta 1512 Asp Leu Thr Leu His Asp Gln Val His Leu Leu Glu Cys Ala Trp Leu 370 375 380 gag atc ctg atg att ggt ctc gtc tgg cgc tcc atg gag cac cca gtg 1560 Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser Met Glu His Pro Val 385 390 395 400 aag cta ctg ttt gct cct aac ttg ctc ttg gac agg aac cag gga aaa 1608 Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp Arg Asn Gln Gly Lys 405 410 415 tgt gta gag ggc atg gtg gag atc ttc gac atg ctg ctg gct aca tca 1656 Cys Val Glu Gly Met Val Glu Ile Phe Asp Met Leu Leu Ala Thr Ser 420 425 430 tct cgg ttc cgc atg atg aat ctg cag gga gag gag ttt gtg tgc ctc 1704 Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu Glu Phe Val Cys Leu 435 440 445 aaa tct att att ttg ctt aat tct gga gtg tac aca ttt ctg tcc agc 1752 Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr Thr Phe Leu Ser Ser 450 455 460 acc ctg aag tct ctg gaa gag aag gac cat atc cac cga gtc ctg gac 1800 Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile His Arg Val Leu Asp 465 470 475 480 aag atc aca gac act ttg atc cac ctg atg gcc aag gca ggc ctg acc 1848 Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala Lys Ala Gly Leu Thr 485 490 495 ctg cag cag cag cac cag cgg ctg gcc cag ctc ctc ctc atc ctc tcc 1896 Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu Leu Leu Ile Leu Ser 500 505 510 cac atc agg cac atg agt aac aaa ggc atg gag cat ctg tac agc atg 1944 His Ile Arg His Met Ser Asn Lys Gly Met Glu His Leu Tyr Ser Met 515 520 525 aag tgc aag aac gtg gtg ccc ctc tat gac ctg ctg ctg gag atg ctg 1992 Lys Cys Lys Asn Val Val Pro Leu Tyr Asp Leu Leu Leu Glu Met Leu 530 535 540 gac gcc cac cgc cta cat gcg ccc act agc cgt gga ggg gca tcc gtg 2040 Asp Ala His Arg Leu His Ala Pro Thr Ser Arg Gly Gly Ala Ser Val 545 550 555 560 gag gag acg gac caa agc cac ttg gcc act gcg ggc tct act tca tcg 2088 Glu Glu Thr Asp Gln Ser His Leu Ala Thr Ala Gly Ser Thr Ser Ser 565 570 575 cat tcc ttg caa aag tat tac atc acg ggg gag gca gag ggt ttc cct 2136 His Ser Leu Gln Lys Tyr Tyr Ile Thr Gly Glu Ala Glu Gly Phe Pro 580 585 590 gcc aca gtc tga gagctccctg gctcccacac ggttcagata atccctgctg 2188 Ala Thr Val 595 cattttaccc tcatcatgca ccactttagc caaattctgt ctcctgcata cactccggca 2248 tgcatccaac accaatggct ttctagatga gtggccattc atttgcttgc tcagttctta 2308 gtggcacatc ttctgtcttc tgttgggaac agccaaaggg attccaaggc taaatctttg 2368 taacagctct ctttccccct tgctatgtta ctaagcgtga ggattcccgt agctcttcac 2428 agctgaactc agtctatggg ttggggctca gataactctg tgcatttaag ctacttgtag 2488 agacccaggc ctggagagta gacattttgc ctctgataag cactttttaa atggctctaa 2548 gaataagcca cagcaaagaa tttaaagtgg ctcctttaat tggtgacttg gagaaagcta 2608 ggtcaagggt ttattatagc accctcttgt attcctatgg caatgcatcc ttttatgaaa 2668 gtggtacacc ttaaagcttt tatatgactg tagcagagta tctggtgatt gtcaattcac 2728 ttccccctat aggaatacaa ggggccacac agggaaggca gatcccctag ttggccaaga 2788 cttattttaa cttgatacac tgcagattca gagtgtcctg aagctctgcc tctggctttc 2848 cggtcatggg ttccagttaa ttcatgcctc ccatggacct atggagagca acaagttgat 2908 cttagttaag tctccctata tgagggataa gttcctgatt tttgttttta tttttgtgtt 2968 acaaaagaaa gccctccctc cctgaacttg cagtaaggtc agcttcagga cctgttccag 3028 tgggcactgt acttggatct tcccggcgtg tgtgtgcctt acacaggggt gaactgttca 3088 ctgtggtgat gcatgatgag ggtaaatggt agttgaaagg agcaggggcc ctggtgttgc 3148 atttagccct ggggcatgga gctgaacagt acttgtgcag gattgttgtg gctactagag 3208 aacaagaggg aaagtagggc agaaactgga tacagttctg agcacagcca gacttgctca 3268 ggtggccctg cacaggctgc agctacctag gaacattcct tgcagacccc gcattgcctt 3328 tgggggtgcc ctgggatccc tggggtagtc cagctcttat tcatttccca gcgtggccct 3388 ggttggaaga agcagctgtc aagttgtaga cagctgtgtt cctacaattg gcccagcacc 3448 ctggggcacg ggagaagggt ggggaccgtt gctgtcacta ctcaggctga ctggggcctg 3508 gtcagattac gtatgccctt ggtggtttag agataatcca aaatcagggt ttggtttggg 3568 gaagaaaatc ctcccccttc ctcccccgcc ccgttcccta ccgcctccac tcctgccagc 3628 tcatttcctt caatttcctt tgacctatag gctaaaaaag aaaggctcat tccagccaca 3688 gggcagcctt ccctgggcct ttgcttctct agcacaatta tgggttactt cctttttctt 3748 aacaaaaaag aatgtttgat ttcctctggg tgaccttatt gtctgtaatt gaaaccctat 3808 tgagaggtga tgtctgtgtt agccaatgac ccaggtagct gctcgggctt ctcttggtat 3868 gtcttgtttg gaaaagtgga tttcattcat ttctgattgt ccagttaagt gatcaccaaa 3928 ggactgagaa tctgggaggg caaaaaaaaa aaaaaaagtt tttatgtgca cttaaatttg 3988 gggacaattt tatgtatctg tgttaaggat atgcttaaga acataattct tttgttgctg 4048 tttgtttaag aagcacctta gtttgtttaa gaagcacctt atatagtata atatatattt 4108 ttttgaaatt acattgcttg tttatcagac aattgaatgt agtaattctg ttctggattt 4168 aatttgactg ggttaacatg caaaaaccaa ggaaaaatat ttagtttttt tttttttttt 4228 tgtatacttt tcaagctacc ttgtcatgta tacagtcatt tatgcctaaa gcctggtgat 4288 tattcattta aatgaagatc acatttcata tcaacttttg tatccacagt agacaaaata 4348 gcactaatcc agatgcctat tgttggatat tgaatgacag acaatcttat gtagcaaaga 4408 ttatgcctga aaaggaaaat tattcagggc agctaatttt gcttttacca aaatatcagt 4468 agtaatattt ttggacagta gctaatgggt cagtgggttc tttttaatgt ttatacttag 4528 attttctttt aaaaaaatta aaataaaaca aaaaaaattt ctaggactag acgatgtaat 4588 accagctaaa gccaaacaat tatacagtgg aaggttttac attattcatc caatgtgttt 4648 ctattcatgt taagatacta ctacatttga agtgggcaga gaacatcaga tgattgaaat 4708 gttcgcccag gggtctccag caactttgga aatctctttg tatttttact tgaagtgcca 4768 ctaatggaca gcagatattt tctggctgat gttggtattg ggtgtaggaa catgatttaa 4828 aaaaaaaact cttgcctctg ctttccccca ctctgaggca agttaaaatg taaaagatgt 4888 gatttatctg gggggctcag gtatggtggg gaagtggatt caggaatctg gggaatggca 4948 aatatattaa gaagagtatt gaaagtattt ggaggaaaat ggttaattct gggtgtgcac 5008 caaggttcag tagagtccac ttctgccctg gagaccacaa atcaactagc tccatttaca 5068 gccatttcta aaatggcagc ttcagttcta gagaagaaag aacaacatca gcagtaaagt 5128 ccatggaata gctagtggtc tgtgtttctt ttcgccattg cctagcttgc cgtaatgatt 5188 ctataatgcc atcatgcagc aattatgaga ggctaggtca tccaaagaga agaccctatc 5248 aatgtaggtt gcaaaatcta acccctaagg aagtgcagtc tttgatttga tttccctagt 5308 aaccttgcag atatgtttaa ccaagccata gcccatgcct tttgagggct gaacaaataa 5368 gggacttact gataatttac ttttgatcac attaaggtgt tctcaccttg aaatcttata 5428 cactgaaatg gccattgatt taggccactg gcttagagta ctccttcccc tgcatgacac 5488 tgattacaaa tactttccta ttcatacttt ccaattatga gatggactgt gggtactggg 5548 agtgatcact aacaccatag taatgtctaa tattcacagg cagatctgct tggggaagct 5608 agttatgtga aaggcaaata aagtcataca gtagctcaaa aggcaaccat aattctcttt 5668 ggtgcaagtc ttgggagcgt gatctagatt acactgcacc attcccaagt taatcccctg 5728 aaaacttact ctcaactgga gcaaatgaac tttggtccca aatatccatc ttttcagtag 5788 cgttaattat gctctgtttc caactgcatt tcctttccaa ttgaattaaa gtgtggcctc 5848 gtttttagtc atttaaaatt gttttctaag taattgctgc ctctattatg gcacttcaat 5908 tttgcactgt cttttgagat tcaagaaaaa tttctattca tttttttgca tccaattgtg 5968 cctgaacttt taaaatatgt aaatgctgcc atgttccaaa cccatcgtca gtgtgtgtgt 6028 ttagagctgt gcaccctaga aacaacatac ttgtcccatg agcaggtgcc tgagacacag 6088 acccctttgc attcacagag aggtcattgg ttatagagac ttgaattaat aagtgacatt 6148 atgccagttt ctgttctctc acaggtgata aacaatgctt tttgtgcact acatactctt 6208 cagtgtagag ctcttgtttt atgggaaaag gctcaaatgc caaattgtgt ttgatggatt 6268 aatatgccct tttgccgatg catactatta ctgatgtgac tcggttttgt cgcagctttg 6328 ctttgtttaa tgaaacacac ttgtaaacct cttttgcact ttgaaaaaga atccagcggg 6388 atgctcgagc acctgtaaac aattttctca acctatttga tgttcaaata aagaattaaa 6448 ct 6450 4 23 DNA Artificial Sequence PCR Primer 4 gtagagggca tggtggagat ctt 23 5 22 DNA Artificial Sequence PCR Primer 5 caaactcctc tccctgcaga tt 22 6 25 DNA Artificial Sequence PCR Probe 6 tgctggctac atcatctcgg ttccg 25 7 19 DNA Artificial Sequence PCR Primer 7 gaaggtgaag gtcggagtc 19 8 20 DNA Artificial Sequence PCR Primer 8 gaagatggtg atgggatttc 20 9 20 DNA Artificial Sequence PCR Probe 9 caagcttccc gttctcagcc 20 10 8566 DNA Homo sapiens 5′UTR (1)...(2302) exonexon junction (1491)...(1492) exon 4exon 5 10 aacaggctcg aaaggtccat gctcctttct cctgcccatt ctatagcata agaagacagt 60 ctctgagtga taatcttctc ttcaagaaga agaaaactag gaaggagtaa gcacaaagat 120 ctcttcacat tctccgggac tgcggtacca aatatcagca cagcacttct tgaaaaagga 180 tgtagatttt aatctgaact ttgaaccatc actgaggaca aacagagata tatcggagtc 240 tggcacgggg cacataaggc agcacattag agaaagccgg cccctggatc cgtctttcgc 300 gtttatttta agcccagtct tccctgggcc acctttagca gatcctcgtg cgcccccgcc 360 ccctggccgt gaaactcagc ctctatccag cagcgacgac aagtaaagag ttgtgcctgg 420 agtgatgttt aagccaatgt cagggcaagg caacagtccc tggccgtcct ccagcacctt 480 tgtaatgcat atgagctcgg gagaccagta cttaaagttg gaggcccggg agcccaggag 540 ctggcggagg gcgttcgtcc tgggactgca cttgctcccg tcgggtcgcc cggcttcacc 600 ggacccgcag gctcccgggg cagggccggg gccagagctc gcgtgtcggc gggacatgcg 660 ctgcgtcgcc tctaacctcg ggctgtgctc tttttccagg tggcccgccg gtttctgagc 720 cttctgccct gcggggacac ggtctgcacc ctgcccgcgg ccacggacca tgaccatgac 780 cctccacacc aaagcatctg ggatggccct actgcatcag atccaaggga acgagctgga 840 gcccctgaac cgtccgcagc tcaagatccc cctggagcgg cccctgggcg aggtgtacct 900 ggacagcagc aagcccgccg tgtacaacta ccccgagggc gccgcctacg agttcaacgc 960 cgcggccgcc gccaacgcgc aggtctacgg tcagaccggc ctcccctacg gccccgggtc 1020 tgaggctgcg gcgttcggct ccaacggcct ggggggtttc cccccactca acagcgtgtc 1080 tccgagcccg ctgatgctac tgcacccgcc gccgcagctg tcgcctttcc tgcagcccca 1140 cggccagcag gtgccctact acctggagaa cgagcccagc ggctacacgg tgcgcgaggc 1200 cggcccgccg gcattctaca gaatggtgct gtcatgtgga ctgtcctccc gagtgtccca 1260 ctggatgttc agagaattta tgtgaaggtc acgtcattta gcattgagat gctgtggtta 1320 ccttcttcca tttcttccat aatatgcagc cacatctatg tgtgaagaaa tgtaatagat 1380 aaaatttctc tggacgcata ataatgtgag aaagattgtc acatgtccca gcaaattgtt 1440 attaatataa atttgttact tggcaagctg agattttgca agatgttact cgccaaattc 1500 agataatcga cgccagggtg gcagagaaag attggccagt accaatgaca agggaagtat 1560 ggctatggaa tctgccaagg agactcgcta ctgtgcagtg tgcaatgact atgcttcagg 1620 ctaccattat ggagtctggt cctgtgaggg ctgcaaggcc ttcttcaaga gaagtattca 1680 agccagaact tccaacacta tgttgaatag gatggtactg gtaccaaaac agagatatag 1740 accaatggaa cagaacagag ccctcagaaa taataccaca catctacaac catctgatct 1800 ttgacaaacg tgacaaaaac aagaaatggg gaaaggattc cctatttaat aaatagtgct 1860 gggaaaactg gctagccata tgtagaaagc tgaaactgga tcacttcctt acaccttata 1920 caaaaattaa ttcaagatgg attaaagact taaatgttag aactaaaacc ataaaaaccc 1980 tagaagaaaa cctaggcaat accattcagg acataggcat gggcaaggac ttcatgtcta 2040 aaacaccaaa agcaatggca acaaaagcca aaattgacaa atgggatcta attaaactaa 2100 agagcttctg ttctttgctg gggtatctga agactgaaaa cacagcaaaa gaaactacca 2160 tcagactgaa caggcaacct acagaatggg agaaaatttt tgcaatctac tcatctgaca 2220 aagggctaat atccagaatc tacaaagaac tcaaacaaat ttacaagaaa aaaggaaccc 2280 catcaacaag tgggtgaagg atatgaacag acacttctca aaagaagaca tttatgcagc 2340 caacagacac atgaaaaaat gctcatcatc attggccatc agagaaatgc aaatcaaaac 2400 cacaatgaga taccatctca caccagttag aatggtgatc attagaaagt caggaaacga 2460 caggtgctgg agaggatgtg gagaaatagg aacactttta cactgttggt gggactgtaa 2520 actggttcaa ccattgtgga agacagtgtg gcgattcctc agggatctac aactagaaat 2580 accatttgac ccagccatcc cattactggg tatataccca aaggattata aatcatgctg 2640 ctataaagac acatgcacac gtatgtttat tgcggcacta ttcacaatag caaagacttg 2700 gaaccaacct aaatatccaa caacaatagg ctagattaag aaaatgtggc acatatacac 2760 catggaatac tatgcagcca taaaaaagga tgagttcata tactttgtag ggacatggat 2820 gaagctggaa accatcattc tcagcaaact attgcaagga caaaaaacca aacactgcat 2880 gttctcactc ataggtggga attgaacaat aagaacactt ggacacaggg tggggaacat 2940 tacacactgg ggcctgttgt ggggtggggg gaggggggag ggatagcatt aggagatata 3000 actaatgtaa atgatgagtt aatgggtgca gcacaccaac atggcacatg tatacatatg 3060 taacaaacct gcacattgtg cacatgtacc ctagaactta aagtataata aaaaatattt 3120 gacataacga ctatatgtgt ccagccacca accagtgcac cattgataaa aacaggagga 3180 agagctgcca ggcctgccgg ctccgtaaat gctacgaagt gggaatgatg aaaggtggat 3240 acgaaaagac cgaagaggag ggagaatgtt gaaacacaag cgccagagag atgatgggga 3300 gggcaggggt gaagtggggt ctgctggaga catgagagct gccaaccttt ggccaagccc 3360 gctcatgatc aaacgctcta agaagaacag cctggccttg tccctgacgg ccgaccagat 3420 ggtcagtgcc ttgttggatg ctgagccccc catactctat tccgagtatg atcctaccag 3480 acccttcagt gaagcttcga tgatgggctt actgaccaac ctggcagaca gggagctggt 3540 tcacatgatc aactgggcga agagggtgcg ctttgtggat ttgaccctcc atgatcaggt 3600 ccaccttcta gaatgtgcct ggctagagat cctgatgatt ggtctcgtct ggcgctccat 3660 ggagcaccca gggaagctac tgtttgctcc taacttgctc ttggacagga accagggaaa 3720 atgtgtagag ggcatggtgg agatcttcga catgctgctg gctacatcat ctcggttccg 3780 catgatgaat ctgcagggag aggagtttgt gtgcctcaaa tctattattt tgcttaattc 3840 tggagtgtac acatttctgt ccagcaccct gaagtctctg gaagagaagg accatatcca 3900 ccgagtcctg gacaagatca cagacacttt gatccacctg atggccaagg caggcctgac 3960 cctgcagcag cagcaccagc ggctggccca gctcctcctc atcctctccc acatcaggca 4020 catgagtaac aaaggcatgg agcatctgta cagcatgaag tgcaagaacg tggtgcccct 4080 ctatgacctg ctgctggaga tgctggacgc ccaccgccta catgcgccca ctagccgtgg 4140 aggggcatcc gtggaggaga cggaccaaag ccacttggcc actgcgggct ctacttcatc 4200 gcattccttg caaaagtatt acatcacggg ggaggcagag ggtttccctg ccacggtctg 4260 agagctccct ggctcccaca cggttcagat aatccctgct gcattttacc ctcatcatgc 4320 accactttag ccaaattctg tctcctgcat acactccggc atgcatccaa caccaatggc 4380 tttctagatg agtggccatt catttgcttg ctcagttctt agtggcacat cttctgtctt 4440 ctgttgggaa cagccaaagg gattccaagg ctaaatcttt gtaacagctc tctttccccc 4500 ttgctatgtt actaagcgtg aggattcccg tagctcttca cagctgaact cagtctatgg 4560 gttggggctc agataactct gtgcatttaa gctacttgta gagacccagg cctggagagt 4620 agacattttg cctctgataa gcacttttta aatggctcta agaataagcc acagcaaaga 4680 atttaaagtg gctcctttaa ttggtgactt ggagaaagct aggtcaaggg tttattatag 4740 caccctcttg tattcctatg gcaatgcatc cttttatgaa agtggtacac cttaaagctt 4800 ttatatgact gtagcagagt atctggtgat tgtcaattca ttccccctat aggaatacaa 4860 ggggcacaca gggaaggcag atcccctagt tggcaagact attttaactt gatacactgc 4920 agattcagat gtgctgaaag ctctgcctct ggctttccgg tcatgggttc cagttaattc 4980 atgcctccca tggacctatg gagagcagca agttgatctt agttaagtct ccctatatga 5040 gggataagtt cctgattttt gtttttattt ttgtgttaca aaagaaagcc ctccctccct 5100 gaacttgcag taaggtcagc ttcaggacct gttccagtgg gcactgtact tggatcttcc 5160 cggcgtgtgt gtgccttaca caggggtgaa ctgttcactg tggtgatgca tgatgagggt 5220 aaatggtagt tgaaaggagc aggggccctg gtgttgcatt tagccctggg gcatggagct 5280 gaacagtact tgtgcaggat tgttgtggct actagagaac aagagggaaa gtagggcaga 5340 aactggatac agttctgagg cacagccaga cttgctcagg gtggccctgc cacaggctgc 5400 agctacctag gaacattcct tgcagacccc gcattgccct ttgggggtgc cctgggatcc 5460 ctggggtagt ccagctcttc ttcatttccc agcgtggccc tggttggaag aagcagctgt 5520 cacagctgct gtagacagct gtgttcctac aattggccca gcaccctggg gcacgggaga 5580 agggtgggga ccgttgctgt cactactcag gctgactggg gcctggtcag attacgtatg 5640 cccttggtgg tttagagata atccaaaatc agggtttggt ttggggaaga aaatcctccc 5700 ccttcctccc ccgccccgtt ccctaccgcc tccactcctg ccagctcatt tccttcaatt 5760 tcctttgacc tataggctaa aaaagaaagg ctcattccag ccacagggca gccttccctg 5820 ggcctttgct tctctagcac aattatgggt tacttccttt ttcttaacaa aaaagaatgt 5880 ttgatttcct ctgggtgacc ttattgtctg taattgaaac cctattgaga ggtgatgtct 5940 gtgttagcca atgacccagg tgagctgctc gggcttctct tggtatgtct tgtttggaaa 6000 agtggatttc attcatttct gattgtccag ttaagtgatc accaaaggac tgagaatctg 6060 ggagggcaaa aaaaaaaaaa aagtttttat gtgcacttaa atttggggac aattttatgt 6120 atctgtgtta aggatatgtt taagaacata attcttttgt tgctgtttgt ttaagaagca 6180 ccttagtttg tttaagaagc accttatata gtataatata tatttttttg aaattacatt 6240 gcttgtttat cagacaattg aatgtagtaa ttctgttctg gatttaattt gactgggtta 6300 acatgcaaaa accaaggaaa aatatttagt tttttttttt ttttttgtat acttttcaag 6360 ctaccttgtc atgtatacag tcatttatgc ctaaagcctg gtgattattc atttaaatga 6420 agatcacatt tcatatcaac ttttgtatcc acagtagaca aaatagcact aatccagatg 6480 cctattgttg gatactgaat gacagacaat cttatgtagc aaagattatg cctgaaaagg 6540 aaaattattc agggcagcta attttgcttt taccaaaata tcagtagtaa tatttttgga 6600 cagtagctaa tgggtcagtg ggttcttttt aatgtttata cttagatttt cttttaaaaa 6660 aattaaaata aaacaaaaaa aaatttctag gactagacga tgtaatacca gctaaagcca 6720 aacaattata cagtggaagg ttttacatta ttcatccaat gtgtttctat tcatgttaag 6780 atactactac atttgaagtg ggcagagaac atcagatgat tgaaatgttc gcccaggggt 6840 ctccagcaac tttggaaatc tctttgtatt tttacttgaa gtgccactaa tggacagcag 6900 atattttctg gctgatgttg gtattgggtg taggaacatg atttaaaaaa aaactcttgc 6960 ctctgctttc ccccactctg aggcaagtta aaatgtaaaa gatgtgattt atctgggggg 7020 ctcaggtatg gtggggaagt ggattcagga atctggggaa tggcaaatat attaagaaga 7080 gtattgaaag tatttggagg aaaatggtta attctgggtg tgcaccaggg ttcagtagag 7140 tccacttctg ccctggagac cacaaatcaa ctagctccat ttacagccat ttctaaaatg 7200 gcagcttcag ttctagagaa gaaagaacaa catcagcagt aaagtccatg gaatagctag 7260 tggtctgtgt ttcttttcgc cattgcctag cttgccgtaa tgattctata atgccatcat 7320 gcagcaatta tgagaggcta ggtcatccaa agagaagacc ctatcaatgt aggttgcaaa 7380 atctaacccc taaggaagtg cagtctttga tttgatttcc ctagtaacct tgcagatatg 7440 tttaaccaag ccatagccca tgccttttga gggctgaaca aataagggac ttactgataa 7500 tttacttttg atcacattaa ggtgttctca ccttgaaatc ttatacactg aaatggccat 7560 tgatttaggc cactggctta gagtactcct tcccctgcat gacactgatt acaaatactt 7620 tcctattcat actttccaat tatgagatgg actgtgggta ctgggagtga tcactaacac 7680 catagtaatg tctaatattc acaggcagat ctgcttgggg aagctagtta tgtgaaaggc 7740 aaatagagtc atacagtagc tcaaaaggca accataattc tctttggtgc aggtcttggg 7800 agcgtgatct agattacact gcaccattcc caagttaatc ccctgaaaac ttactctcaa 7860 ctggagcaaa tgaactttgg tcccaaatat ccatcttttc agtagcgtta attatgctct 7920 gtttccaact gcatttcctt tccaattgaa ttaaagtgtg gcctcgtttt tagtcattta 7980 aaattgtttt ctaagtaatt gctgcctcta ttatggcact tcaattttgc actgtctttt 8040 gagattcaag aaaaatttct attctttttt ttgcatccaa ttgtgcctga acttttaaaa 8100 tatgtaaatg ctgccatgtt ccaaacccat cgtcagtgtg tgtgtttaga gctgtgcacc 8160 ctagaaacaa catattgtcc catgagcagg tgcctgagac acagacccct ttgcattcac 8220 agagaggtca ttggttatag agacttgaat taataagtga cattatgcca gtttctgttc 8280 tctcacaggt gataaacaat gctttttgtg cactacatac tcttcagtgt agagctcttg 8340 ttttatggga aaaggctcaa atgccaaatt gtgtttgatg gattaatatg cccttttgcc 8400 gatgcatact attactgatg tgactcggtt ttgtcgcagc tttgctttgt ttaatgaaac 8460 acacttgtaa acctcttttg cactttgaaa aagaatccag cgggatgctc gagcacctgt 8520 aaacaatttt ctcaacctat ttgatgttca aataaagaat taaact 8566 11 392000 DNA Homo sapiens unsure 137740 unknown 11 tcagagcatg ttattcaata atctaccttt caccagaaat cataataaac acaataaaaa 60 tgcttacaga acccccacaa tgcgttagta tacatgatta ttccttgtgt aagtgaatct 120 tgttgagatt ttatgttcag tcaattgcaa ttaaatactt tacatattaa ctaaaatgtg 180 tcctgctcta tgtattctgg agaagttact ctcagacaaa tttacatatt taaattattt 240 tatgggctaa ctgataagta tagagaagac tgaagacagt taagatcatt gatttcaaaa 300 tgttttaaag tgttgattat ttattttggt tttctttctt tcccatgcca gttttgagat 360 gcacctctta cttggcaggt gttcctctgt actgggtact gggacagaga gaaatacagt 420 agcaagaggg agatcctgcc tccgccccat tctaccattc tcactgccag aaagccagcc 480 ttttttcaag gcttgtagag aagaaaaaga gaaaatattt ttaaaaattc atttaaagta 540 cctactgcat aaaccacacc agacatgatg agatattaaa atgtcaatat tattaaaaat 600 ttttaatatg attttacagc ccctttgcta ctttaaaatg tttatcttag tgttaaacaa 660 acaatcaata acctcataaa cttaaaaatt gctgcaggaa ataccggaca gtttatggaa 720 ggatcatatg acagaaggaa gggctgaaga gtgtgagaag ctagacctct gcaggttacc 780 gaagtcaaga acctcattaa tcggtaacaa gaagtgcaga gcgggctttt gagtccatgc 840 ctgagtaaga aagtcccaaa aaacactcac agaagatatt tccttgcccc tgcttttagt 900 ttagctgtag ctaactttgg attaacaaaa tttatgtgct gaatgatgtt ttattttttt 960 ttccaactcc acatgcctgt ctagacttca agctttatta cgaataaaga gaaaatcggc 1020 tggatggcat aaaaaatatt tcaggcagat taacacatga tttacctctt cttgaacatc 1080 catcttaatg gaagtgctaa gaaagttaga ttcgggcctg gcttggcaaa agcaaggcca 1140 ccccctcctc tattttttca atgagatttt ccaatcctag tcaaatggtg gtgctagttc 1200 tttatttttg agttactgca tttcctaatt tcatggtcat aacagcctcc tgtctaccga 1260 ctcagaacgg attttaccaa aactgaaaat gcaggctcca tgctcagaag ctctttaaca 1320 ggctcgaaag gtccatgctc ctttctcctg cccattctat agcataagaa gacagtctct 1380 gagtgataat cttctcttca agtaggtact cctatttctt ctcaatttat tttttccttt 1440 ttgatataat gtgctactgt ttacaagcat attgtaactt cagagcttac ctctcatctt 1500 taaaaaatgt tcattttttt gtctttctgc tccaaggata ttttgcaaag ttactggcaa 1560 gtattcctgg gatgataaaa tgtgaaatct aaacttggta cagtggaaat tcacttctag 1620 aataatattt agctgaggca gagggcaatc cgactaccct tttcttagta cagcacacac 1680 aggctgcctg tctgttccag ataacataaa tgtattggat ctagcactag ctaggagaca 1740 ctgtattgtt gaactgtgtt agaattttat aagctcttaa ttggacaaat ctcagagtag 1800 catgaacaca ctacctgttt tctgaatctt tggagccata acttacgtga gtttgaacta 1860 agcgatgtga ataagccatt atttgtttcc taaaggcagt caagttttct gaaaagctac 1920 acatttagca gcaaaagaac gagcccctct gtcttgaaat gggcctctga ttttaagcaa 1980 gctcttttga gtcctggtgt cccattttct cagttccttt ttgcctcaca atggcacata 2040 cataatgact ccaccacata tagcagtggg ctactcgggt aatgatgtgg cagtcacaag 2100 acagggcaga atactttcat tttggttaga ggaatgccac atgtcttagg aaatgctcgc 2160 tgaactgtaa gtttcatact ttgtcaagaa gataaccagt attctctcaa acaagtccgt 2220 aggagccaac atgattaaaa gattttaaag caatttactc gatagaaggg ttgggcttaa 2280 tcaggacttg tgatcatggc aatggttcct gcttaaaggt gccagatttt taatgccttt 2340 atgtgccaga tctaataggc ttacagagca actccatgta tatgaggttg ctgggaaact 2400 catctggttt tgaatgtggt atatacatat tttaatattg agagtaaaca ggaagaccag 2460 gtagaagtat ttgaactgaa ttctgaaacg tacagagaac ttaaattgga tgagaatgtt 2520 tgagaaccat ggatggttca gggtccattt gtataccata aaatcccttc ctatttctca 2580 aaagcaaata ttttctttga ttttgttaat atcctgtgat gactgcccac taggccttgg 2640 aatgcatgca gataatgctg tagcagttgg ataaaatact ctagaatgtc agattttcaa 2700 ggaaattaca aataaaaaca atgtaggtaa aagatacgac atgtaggaaa aaagcaaaat 2760 tttccttaag aatacaagcg tcgtatttac gagtagaaga tttttcttgg acatttggag 2820 atacgtgttt cattttattg cttgtgacag tcaaggaaag gaataaagct cttgtgtctt 2880 aaacttgcag caagaacaaa gtccaactat ctttcgtttc tgataactct gtgtcttttt 2940 gttcaatatt gggtttagag ctagctacca tctaccttcc cttcaaacac tcactctaaa 3000 cctccacaca gtgtaagtat ttacatcagg catctgctaa acattttcac atggttatct 3060 gcaggtcttc tctgagtctg tctgcattca tttatcctag ttgctcagaa caatcgcttg 3120 ggctgacggc ctggtggttg agtttacttt gctttgaata gggaacagct gtgctccagg 3180 actgcagatt ggctattcgg aaaaaagggc aaggaagaga gtgacccagc tctgggtaga 3240 ccatccacac tgtaaaaaaa aaagtcatag catagtcttc atctatggca gtggagatat 3300 ggtcctgtcc atccacctct atcaggagag ggtctccatt gttaatctcc gagaaagagg 3360 cgccatctgt gaaacctcct gcatattgtc taatgaagtg ctattttgaa aggcgtgcac 3420 tgtacaggta agagtgatga tggtgtgcct gccttctggg caacatctca gtagacttcc 3480 tctgaatcat tcccactgga cccaacagca aaagcgtaca catcattgag ttttatcgtt 3540 ctatctaagg cgtataacat ttttctctct gaaagtctgt gattctttcg gagaatgaag 3600 gggcttaccc tatccatctg cccctaaaaa tattcgctgg aaagctgata cctctgctca 3660 ggttttccac agcagatcac tcttcagtaa gaattctgat attaagtagt ttaattcaga 3720 tccatggaaa atgactgagt accagccata gctcccacca ctctctagct gtgcaattta 3780 gaggcagatt atttaacctc atgccttgaa tttctcatct gcaaagtggg agtactaaca 3840 gtagctacca gatatattat atggaataaa tgacattaag ccactcatta aactccttgc 3900 agtttccaag cattagaaac tcagtatgag gaagttattt ctattctaag cctagcacag 3960 tgcctggtac tcaatacatg ttggttgaat cagtgaaata attcaaggtc agcaccaaag 4020 ctgctaggaa tttatgaaca tctgatcata actggaaact tgatctaaaa agcaaagggc 4080 agtcaatcca atcaactgag cgtaccatct gttgaaatgc tgctgcttct gtaatgagta 4140 taaagtgttg gaagagaaag tccaggaacc tccatcattc ttccatcatt cctctccttt 4200 gtgactatct ttgtgatgag aagggtaaca aaaaaatctt gctgagatga gcgtgtcaaa 4260 aacgtgttac aaatgcttca cattcccttt cacatcaaca gaagcatgtt gcttcattgt 4320 tgggcaatgt cttagtccat acacacatag agctctatgc tgattttttt ttgagatgga 4380 gtctcgctct ttcaccgagg ctggagtgca gtggtgcttt ctcagctcac tgcaacctcc 4440 gcctcccagg ttcaagcaat tctcctgcct cagcctccag agtagctggg attacaggca 4500 tgtgccacca tggccagcta attttcatat ttttagtaga gacggggttt taccatgttg 4560 gccaggctgg tctcaaactc ctgaccttaa gtgatccact cgccttggcc tcccaaactg 4620 ctgggattac agacgtcagc cagcataccc ggttgtatgc tgatgttcta attcaatgtg 4680 ataccaaaga cctgagatag tctctcccac tctggcccca taacatatgt ccacgaggtg 4740 gtaataataa caactatagt agcacctaag gttggggcag ctcttacttt gtgcgatgct 4800 ttttatagtg ttattacgtg tgattctcac agcaacccca ggtggtgaac aacgttatga 4860 ttcctgttgt acaaatgagg aaactaaggc tttgcaaagc taggtaacat gcccaatatt 4920 acacagcttc aaaagtgaca gccctaggac ttgaagataa actcatctaa ttccaaagct 4980 catgctttta gccattactt gagacagtat taacttttaa agtttgtaat caatatgaat 5040 ttggccttgg gaaagcaggt taagcatctg gggttgatgg gagataacat tacaccctct 5100 cttagcctca gcaacttcat ctgtaaaatg ggaataatta catccgagtc acagaagttt 5160 tgtggctctt catgaggatt aaataaagta atgcatgtaa aagagttttg tacaaagttc 5220 acttttataa aatgcaagtt gtggccggga ttggtggttc acgcctataa tcccagcact 5280 ttggggggct gaggtgggtg gatcacctga ggtcaagagt tcgtgaccag cctggccaac 5340 acggtgaaac ccgtctccac taaaaataca aaaattagcc aggagtggtg gcatgggcct 5400 gtaatctcag ctacttggga ggctgagact ggagaatcgc ttgaacccgc gaagtggagg 5460 ttgcagtgag ccgagattgt gccattgaac tcccacctgg gcaacagagt gaaactgcat 5520 ctaaaaaaag acaaaaaaaa aaaaagtaag ttgttatatg caatgcataa attattactt 5580 agttccatgt aaaatcttcc cactaagtga atgagggttc acctggctgt agtgctatga 5640 gatagatatg aggggcagat tggtttatgc ttctcaaaaa cagaaagtgt gccagggtgg 5700 aagtgtgggt ggggagtctc cgcctcccag ccatgtggca aagctggaat gtgagtacag 5760 cagcagtatg gatgcggttt tgaggggatg gtggtaatcc tcttctggcg gcacccctcc 5820 agtattgtgg gatgctctct gatttctttt gagaagacaa gtagctagga gcttccctag 5880 cctttctgtt gtaaaaacca tcaagatccc tgttgaatgc atacctggag cttggtttcc 5940 ctaagcacag actttaataa cttcatttgg atttagtctc ctatttaaag ctgccaccca 6000 ctctcaattt tttgggtttt cctactaaga atggatataa catgggcagt cttccagttc 6060 tcctttcttg ctgccttgaa gacaacacac aggccaatca caaggaggca gagacaggcc 6120 ccaacaagtt gacaatccta gagagcttag tgtgagtaga cttgctgagg ttcctgactt 6180 ttgctggaat aggagagtgc cactggcttt ttgacatttc tttttccaac tgtttccttg 6240 tcaaaatgac cagcagctca gctcccctaa acatacctcc tcccctagat tggttcagag 6300 gaagccatca aggtcctttt gcaaacggat gatctgcatt tttgagatcc ttctttcctc 6360 tgctgttcat agaaatggtc tcattggaat aattcctttt ggaacgttac taaggacacc 6420 aagaaatcaa caagaaaatt tgagtgtatc tgacagaaga aatttggctt ttgtactcta 6480 ataattattt attagaagca ataactggtc agaatttatt tgcttaaaac catgtaaaga 6540 aaggtgctta ataaagataa ttgcatcaca tatagtaatc cgttttagta tctttcacct 6600 taaaactatg tgacaaataa agacacaaat tgctctttct ttctaataag caattttgga 6660 aattccttat tgggaaattc caaattttac aaaatttaca aaatttaaaa ttttggaaat 6720 cgtacctgca tcaagttttc tgaaagaata tttaaggatt aaggttactt agaatccaat 6780 atatgcatag tttaatttaa ctcatattgt taaattcttt ttctaatttt atttaagaaa 6840 tgagtaatat tgacaagggc cttgctgtgg tttattatgg cttgtcctag agtctctatt 6900 cccagctaga ttaaaagtgc ctcagggctg ggcatggtgg ctcatgtctg taatcccaat 6960 attttgggag gctgaggcca gtgaatcagt tgaggccagg agtttgagac cagcctggcc 7020 aacatagtga aatgctatct ctactaaaaa tacaaaaaat tagccggaca tggtggtgca 7080 tgcctgtaat accagctact tgggaggctg aggcaggaga ttcgcttgaa cctgggaggc 7140 ggaggttgca gtgagctgag ataacaccac tgcactccag cctgggagac atagagagac 7200 tccatctcaa ataaataaat aaataaataa ataaataaat aaataaataa ataaataagt 7260 agtgcctcgg gtgcatagat ggggttgttc agttttctac cctgtgcctt gggaagtgcc 7320 tggtacacac tggtgtttgg cacataattg tagagtgaga ttgagcctgg catgttcctt 7380 gatccctaga caatctctat caggtgtgat cagtaaggca cataatatga tatgtgacta 7440 ttacagagta gcacactaca atatgtgcct aaagccataa catcaactaa tacaattcag 7500 cagagtagaa tgtgaagagt gcttgcagag tgctgagcac cacggtgagg aagtgtaaac 7560 agaagaaggt atttctgggt tggtgcagga tggttaggga tagctttggg taggaagcga 7620 ctcttgacca tgaccttaaa ggacaggtaa tgtttacatg ggaaaataca aggaaaagga 7680 ggtgcataat gaaaggcatg ggggaggtgg ttttgggaaa ccatcagtct gacagaaaca 7740 tagttaagaa aagtgcaagg tggtggtagg aggtaattta gaagtggaga gtcagatgtc 7800 ctattaagga gcttgaactt tatcttgtag gcattaaaga tgttggtgta ggattggaat 7860 gaaataaaga cttaacctta gaaaaatact gtgtggattg aagttttcag atgaagagtg 7920 ggtacatcaa ttcggaggtg agggaaatag ttcaagggag gtgtcacacc attaaaaaaa 7980 atcttttagg acttgttttt tgcaatcatg attgtttatg gttgtaaaga ttttgtttca 8040 gaaatgattg gtggagaaag aagtgtattg agaatcaaaa gatgggactg tgccactgat 8100 gtgcgcagtg agaagctgca agcttggtgc cccatcttcc taactgtaaa atgggcataa 8160 caactaccag acagccgtca aaacattata ctagtgatac aatgaagact aagtgatata 8220 attttgaaag gcagtatgcc ttatatgtgt aaaatgctgt ttacttggaa tatttttata 8280 gtaaaattat tttctttgga caagatatag atgcagaaga aaatgatcat atttctgtga 8340 gattaggatt cagaccattt gaatttttta tatttattaa ataggtactt tatgttgggt 8400 actgaataag tcttttattt ttaacacctc atttccctca caaaatggat ggcatctttg 8460 gactagggga aatgtgtggt ccctgcagct gtagtatttt atgattctat agcttttgcc 8520 tttagcaaac ttctcttaga atagtgattt aagggctggg tgtggtggct tacacctgta 8580 atcccagcac tttgggaggc tgaggcaggc agatcacctg aggtcaggca ttcgagacca 8640 gcctggccaa catggtgaaa ccccttcttt actaaaaata aaaaattagc cccgtgtggc 8700 agcatgcgcc tgtagtccca gctactaggg aggctgaggc aagagaatcg cttgaaccgg 8760 gaggtggagg ttgcagtgag ccaatattgt accactgcac tccagcctgg gcgacagaac 8820 atttaatgct ggtggctcac acctgtaatc ctagcacttt gggaggccga ggtgggtgaa 8880 ttgcttttgc tcaggagttt gagagcagtc tgggcaacat ggcgaaaccc catctctata 8940 aaaaatacaa aaattagcca ggtgtggtgg tgcacgcctg tagtcccagc tacttgagag 9000 gctgaggtga gaggatgact taagcccagg agatccaggc tgcagtgagc tgacatagcg 9060 ccactgcaca ctgcattcca gcctgggcaa cagagcaaga tcttgtctta aaaaaaaaaa 9120 aaagtgactt aagatactga cagtataaac acaaccaaac ccatgggcat ctgtgctggg 9180 aataaaagac agacatgttt tcattgcact gatttaggat tctgcttgga aaggaaaact 9240 gtgatctctc ctgcagttgc ctaaaatgct ttacagttat gggaatggaa aagctaaatt 9300 ctgtgatttg tgggtagagg gaaggaggac gagtgtcctt tctgatttcc tctttttcct 9360 tctcttccaa ggggaaataa aaggctagag caacaattta aaaagaaaag gcaaggagct 9420 actgggggta gagtcgggag ggaaaaaggc caaacccact aaataatttc acttcagtta 9480 cagtaaatct caaatgatga tgctacactc ctgagaatgt tccatggtgg aaatgcctgg 9540 gctttgaatt ttgagcagcg aagtaccagg agagggtgac atgataacat tcaacaggaa 9600 gaacactgct cttgtccgtt tgacggtcct attcctccgg atcactcaat cttcacaaat 9660 caagcatata gctccttcac atgtcatttg tgaagggaaa gactcctagg aaaatgtttt 9720 ctaggaaagg gaaaaaagca gaaagcaaag gtctcctgct tactacagca ttcgtgttgc 9780 ataagcagta ttaatgtagt ggagtattaa tcacttagaa cagttcacgt attattccta 9840 tctgggctct gcagggtcct ttcttcactt ctttctcgac atttggattc tgtccatttt 9900 actcctccct ctgcacttgg aatagaagtg aaatttgttg tgccaattct ctgcttgtta 9960 gaagccatgg taatgtttag taggggaaaa gatttgtact gctacataga aggaggtttt 10020 gggattattt aagactttac tttgttgatg ggattcctag aatctactat tactgggtat 10080 actagacaag tttgtagatt tacaaaagtg tggataacat gggttgcact tgatttcttt 10140 atccagctct ttggttctaa atttattgcc aattttattt atcaaaacta ttctcagcgg 10200 agtagtattt tctgtggaca caaggaaaca tctgtgagct taaaccttag aggcagatag 10260 ccagttagaa catttggcat atgaagctta gatagcagaa gagaaaaatt aaccaaggca 10320 accctcaaaa atattgagaa ggcaactaag aaaaatttct tatcactgac agactgcagt 10380 attgagttcg tgttaatgaa gaaatgtcag aatacataat gaatcaataa ggagtgtcat 10440 attatggcaa gtttcaatgt tggtgtcaat ctcgactgcc aggatttatg gtagattata 10500 taatggaatc ctgagttctg agagatcaaa ggaaaatgct ggctctttct tcatccattc 10560 tcttaggtca agcctatgca gcaagaagcc aagttgagaa ttgagcaatt atctgaagtg 10620 ggcagtggag acggccaaac cagataatat ataaccagaa agtcaccgtg gagggaaaat 10680 gtggactgaa aataggataa ggggtggagg tagaatgtca agccatttgg tcagtgtcca 10740 cagtccaaat ttactgaata acagccaatt ccttacttca tgtggttatt tagagcgaga 10800 ctagaggaca agtgaaaaaa aaaaaaaaga gttcattcct aaggttgttg catgtttgtg 10860 caaaatttct tcaaatctct gttattatct gttacatgtc taattctgag tacttccaga 10920 gattgcattt cattacttta gattagtggg ttgaagtggt ggaggaagcc catataatct 10980 gacttacatg gagaaaacaa gtcttttttt atagtttagt tgagtgttat atttaattag 11040 cctttttttc cctccataat gcatgcttat gaattttcca cttaaaattc tgaggctctg 11100 acctttatca tttcctcatg gagcaatttc tgtacctcct taactttagt agaacatagc 11160 aatgaaatat acaagtcccc tagaatagaa tttgtgtgaa tttggttttc taaaaacaca 11220 actaccaaag tctgaggacc agtgtggtat ttttttcttc tatttgatat ggaaaccata 11280 aactacttac tttgagcaga tgtttcccag tcctaaaata cagctatcag tccactggcc 11340 cctataaatc tgttggagtg cacctgctaa ttctgaagcc tccctaatac aatgttaaac 11400 tttccttttt tttttttttt tttttttgag aaaaaaattg taaattaggt tcactgttgc 11460 ttggaattag gaaaaaataa aaacacaggc atactaatat ttcagatgga aaaacaaagt 11520 taagaattca acaagttttt ttcccccact ctatcatgtc ttgcacattt aaagctgtta 11580 tacaacattt taaaaacaaa ccaaaaaaac ccagggcctt tttccaacag cttaggctga 11640 tgacccacag taaaaaagtg ccccatggga tattcttaaa gcaccccaag ggagtctatt 11700 gaaataactt aaagtaaaaa ttcagaagaa ttttacatgt aattaaaaat taagaacgtt 11760 gttttataag caatagggaa aagctgtatt aagttgcatt gctcaatttc tcacttgctc 11820 tgtgcagtga ctgctttttc aaccatgtaa caacgtctga atcttcgtgg taaaatcata 11880 cctatcacag ccacagcagg ttttgttctg ctgctgcaca tgtgatttga gatactgtgg 11940 gctgggagtt tttttttttt taatttctaa tggcaaaatg gatctataga aatggaagtc 12000 atctgtaatc tcagcacttt gagaggctga ggtgggtgga tcaccggagg tcaggaattg 12060 gagaccagcc cagccaacat ggtgaaaccc atctctacta aaaagataaa aaattagctg 12120 gcgggcgtgg tggtgtgcgc ctgtagtccc agctacttgg gaggctgagg cagaagaaat 12180 gcttgaaccc aggaggtgga ggttgcagtg agccgagacc gcaccgttgc actccaatct 12240 gggtggcaag agcgacacta catctcaaaa aaaaaaaaaa aaaaaaaaag aagaagaaga 12300 aatggaagtc atcccgtggg cctgagttgg tgtagtggat tatggcctgt gcgtgaatga 12360 agaaatactt gccaatggca tcagtggtaa ctagcttaag ccctactcag ctttgtaaaa 12420 taatgtaatc aaggaatttg atctgaacag gtaagccaaa cattgattct tcagtgccta 12480 ttgataagtg agactacttt tctttttaac agccttattt cacttaagtg gggagtcaaa 12540 ctagctttaa ttaaggaaat ctgtagaaat cacccacatc tccctttcct tctctgttaa 12600 aaaaacaaaa ggaagaagaa aactaggaag gagtaagcac aaagatctct tcacattctc 12660 cgggactgcg gtaccaaata tcagcacagc acttcttgaa aaaggatgta gattttaatc 12720 tgaactttga accatcactg aggtatgtgt gaacatacta gtttcctctt tctctctcct 12780 gactttgtcc gtgaattgat aagatctaat ttggtcatca gtttggagaa cgatttttca 12840 tttaatttct ttcattatca agtgtgtatt gtcaggggct tagcagtaca cctactatct 12900 gatgggcact ctacatgcgt tgcttaggtt gaaattaagg atacaatctg tgcactacca 12960 ccatttaaaa aaatccccaa gtctactgtg tgggtgaggt ttctttgcat agtatcagag 13020 aggttaacca atttatttac atactcaata gtccactcta agtagggaaa atccaagctt 13080 tttttttctt aagaaagagc ttttcattct tttttccctc agagctttac catagtttcc 13140 agcaagtgaa aacatttctt gatttgaatt tcacaacctc cttctcctct tgccagttgt 13200 atggtgctaa taggaagcaa aatgtgagtg tgcttttaat ttaaccctaa aataggggaa 13260 tatcttcaga atttagactt tacatattca gtgacctacc taaaaataga gacatagttc 13320 taaccttctc aatcattaag aaacatttct attgaattta attattcaaa acaacaggta 13380 gcagtttcac aagggaaaag acaagccatg ccacttgtat ttgtggtcac caagtaatta 13440 cattattttt tatttaaaat taagataaaa taacttactg actgtcaagt ccatttctca 13500 tttcctccat agaacatttt aaaactagtt cacaaacctc ttgaaaagtc atgcctctag 13560 aaagtgcaaa ttgtcaccat tgcctagaag ccaacttgag aggctgtgta tctatgcagc 13620 attttgcaaa tccagtagca ggcatgtgat ataaaagatt aaatgcaccc ctgatttgtg 13680 aatactatcc tagccttcaa aatgttcaaa agcacaggaa gtctgcactt ttaaaaatat 13740 aacctgccca aattgcaagg gaggggttgg gtgtaggacc taggtctgtc tgccaatcag 13800 cttgagatgc cagtggacga aacctgactt cactaaaaac cagactggca aatattactc 13860 agcgtggtaa tttcctaatt gtagaactgg cctgtttggt gaagtatttc aggaaaattt 13920 ttagctggac cttttctacc ctactgcata agaaatgaag gtttctaggc aaagacttta 13980 cttagtgact aaccaaaaat ggtaaataaa gtcaccactt ccaggcttag ctactgtcct 14040 caaaacagct gcaggactgg tcaggccagt cttctgaggc tggaggtgca tgtggaaccc 14100 ccagagcctt gtctgcaagg gcatggctga ctgcaggctg tttagaagca ccccgccccg 14160 tgaaactcct ctggcttagg aattttaaac agttctagtt ctaatctctc tgctcagagt 14220 ctgagcagct gtgaatgagc tctcctgtga atcacagaaa tgttaatggg tgagctgctc 14280 tagcttctta cttccaagtg gaaggcgcct gtagctcttt gccagcttga tgcagtgagt 14340 ttgattcctc ttttgggcag cagggagaga taatgaagga gggggaaaaa agattttaat 14400 atagaaacga gtcttccatc tggctgaggc tgaacaaagt agaagaacca gtgcaagtca 14460 ctgggggtat ggatctcata ccattttcag catatacctc cctttctctc tttttgattc 14520 tacacatgtc agtccctgag tagtcttgca ttgctttccc cactttgaag tcttagatcc 14580 aaaactttga ttccagaaag gtctaaggtg ctgttgctga gattttgaaa gagacctgag 14640 acaaactgtt gggattctag acgctattgc gcatctgcct gggtaactgt gtcacttagg 14700 ttgggtcacc agaataattc tcctccattt ttgctgcctt tccaatttat aaacaacaca 14760 gaacatcagt ggttctccca taatcaaata tatttggctc tattaatatt aaaatttgat 14820 cttgagtaga aagattctaa gggctaaaaa ataaaagatg taaaatgtat gttgataggt 14880 tagtgtagaa gccacccatg gggttgcccc cactcccact ctttcatatt ttttttaaga 14940 aacaacactc aagttacaaa gtcgattctt tttttgtttt gttttatttg agactgagtc 15000 tcactctgtc accacccagg ctggagtgca gtggtgcgat cttggctcac tgcaacctct 15060 gcctccccgg ttcaagcgat ttttcctgcc tcagcctccc aagtagctgg gattacaggt 15120 gcccgccacc acacccagct aatttttgta tttttagtag agatagagac agggtttcac 15180 tatgtttcac catgttgacc aggctggtct tgaactcctg acctcaggtg atccacccgc 15240 ctcagcctcc caaagtgttg ggattacagg cgtgagccaa cgcccctggc cacaaaagtc 15300 aattcttaac ttaaaacata aaagttccat ttcttttatg gtctacttag tcatgtctgg 15360 agtcagtgag ctcagtcaag tagtttgcag aatgacagtt gtgataccta ttcatttacc 15420 caccagatta ttttctgctc tccatggcac tttatagaaa acagtttatt cggtcattac 15480 aacagctcta ggagggggtt tcattaaacc cactttctag gaaagcgaac taaggcttag 15540 aaaaatcaag taatttgcta aagactaccc agctggcaat gatatgacag gacatgaact 15600 taggacaata actcaaggtc ttggtccctg taaatatggg tttccaggtt atgtatgcag 15660 gcagagggct tagatcctga agtttccttc agaaacttca ggatctaagc cctctatata 15720 ggagcagtat aaaaaggaag gatctcttcc catagggagc ttgtcatcca ttgaatgagg 15780 aactcagact tccactgtga aatgatattt gtatccccat tgtgtgcgag atatggggac 15840 tctgatcatc ataagagcac atttttcctg cctataaatg atacttaata gagctgacag 15900 attatatata tctggaacac ttttacctag cagaaagaca acaggctagg attagctgac 15960 taataatttt atttatcaag ctcaattccc atgctgactt ctcttcctct agtgaaaatg 16020 tgtcatcaga tttggtccca aactggagag gtgaaaggat cctttgacca gtataatagc 16080 catgccatca gttttgcttt cctaattaag ttttatatgg gttaatgatc tatatcatta 16140 ttttgggggt ttctaaacac atatgaacta aagatggaaa agatgatgga aaagatggaa 16200 agaagatgac tcagatgtac aaaggcttgc agagagaagg ataagccaaa aaattggtaa 16260 atcacacatg aataatcaag aactgactac aatataataa tatgtgtcca tttccactaa 16320 tgaataagct gccattatgt ctcttcattc tctatttagg acaaattact tctctgctgt 16380 atttccattc ttacaggtac ctatctgctg tgatttttcc cagttttgac tttatcttgt 16440 tgctttaatc ttgtctctaa gtaagctgca acccagtaaa tatattccag tattgtttat 16500 tgtaattcct gcctttatgt caggtggcaa gaggaaggga ctggttttat taatttatca 16560 gtctgggtgt gtgctaagag gatccttagt acatgctttg attatggtag attgagtcta 16620 aaagattcag ctggtttatt ccatttattt tggtctgtct acctaacaag gtcacacagt 16680 ggattatact agttttctat gtgtcatatt gttggcctga cacataatag caaataagag 16740 gtaccagaat tttctgtaca gtctgaagct gtgtgtgtac aacaaccagt gaaaaatctt 16800 agttatttgg acttttgggt tccatgatgc cagagaaagc cagacaccag cagctggaat 16860 cagctaagac ctaagaccct gcatgcacat atagatgttt acattttctt cctattgcga 16920 cattcagcca ttgctttggc gcctatttca ataatatatt gctgctcatc aaagtggaaa 16980 taatgttttg ttactagctg agtattgaaa agctcttcat agttttgtga ttttgactca 17040 gctccaacat gcaggaccca tttcttcaac tgactttggc aacaggagag attgactagt 17100 gggcttgaaa gtgatccact gctgtttctg tttaactttc ttcaatccta ctgggtcttg 17160 ggaagaagag gtagcgggca tccttgtttg cctcaaccag gaagcacaag gccatcccag 17220 ggcggggcag gagagaggtg ggagggaaga agcaggctcc acagggccat tgtttacctt 17280 gttggcgggt caggtcttct cagggtaggg ttcctgggat aagagcaaag cttattggtt 17340 ttccttgctg tgccacgaga gcacaccaga tcacccctgc agccttgctt gccttcccac 17400 agcctgccct tgcctagggt ttcagctgat atcctttcta ctcaggagga gaaaccacag 17460 aacacatgga ggaagtgttt ccagtgttaa gactttagac caaactatag aaatctgttc 17520 tacctggaaa cctgaagaaa taaatcatga ctgctattca gtagaagtaa aataaaaaaa 17580 cagctttact ggtttggaat cataggaagg ctttctgtat agcctctctg agagctgcct 17640 attggaagga tttgtcctca aaacgtgagg atttgtggtg ttccagggtt tatatgacac 17700 tggcaggata gtttgctaga gggctgtgct tcgaccttta tccaagggat gtaagccgtg 17760 tgtttaggtt agtgagcgtc tagcacaaag ctctaatgtt gaaggagcat tggaggcagg 17820 ctgtgcctct gaacatgtag aattgactag aaatgccaat gttcatttca aaatgaaatc 17880 attatctttc ttatgcttcc atttaaaaat gattattaca tttttgcata tggttgaatg 17940 catattaatt ttagcaagtt tagaaaagag ataagcataa agacatacat aaaaatcact 18000 tattctcatc agctatagat aatcactaac aatattttag gacattttct tttcatcttt 18060 ttcttagcaa tatgtatgtg tgtgggtata catatttaag tgtgtatata tgtaaattaa 18120 aaaacataaa atattcccac aatataatta ataaaaatct aagatacaac acaatttccg 18180 tttgtaatat gtagtgtata tatgtatata tacacattat atgtatatat aaaatacatg 18240 cataaaatag atacacaggt atatattttg caaattgaaa tgatgttgta tcttgtagat 18300 tttatttaac attagaattt atttacacta cttaggtgtt ttaacaagga ttgtggtcca 18360 ccatttattt ccttaagagt aattccaaaa agtggaaata gaatgtcaag gggcaaagtt 18420 ctttataaag tccttaagga gtattgccag atatattttt ttttacttcc ttttaaaaca 18480 tgattgtatt gtagaagttc tctttaaaaa ttccaagcaa aaatttttca aaatcccatc 18540 tagaaatcaa atcatgattt tatttggcta tgcctcttgt agtccttgtc tatgaactta 18600 ttctattatt aaatataata ggtaatttcc actaatttga cagatagaat tttatttttt 18660 acattttctc ttgttacagt gccatgcata tttctattat gttacagaga tcttgggggt 18720 cttttttcct ccctttttcc tttctctttt cttgttctgt accccttcac agaaaccaac 18780 aaatacaggt tgatgtgtat cctctactct tttctccatg ctcacacaac ccaatattta 18840 cacatgcact gatttttcag ggcaatggtc cttctttatc ataaattgtg ggataaggtt 18900 atatacataa tatatgtgtg tgtgtattac tctgaatctt ggttttgtca ctttgcaata 18960 tgtcttaaag attctgataa atcttataga tctatctcat tcttttcagt agttgcatgc 19020 agtataaatt tactataact tattcaagta atctgctttc agctgatact ctgttgtgaa 19080 cagttttcaa catataaaaa agtgctgtca ttacaaatat tcttagatat atattcttag 19140 taattggggg ttttattgtt atggtgtaag tcccaggagt agaattgctg gtttaaaagg 19200 tatgtgtatt tttacatttc tattggtttt ttcatattat tttctaaaaa tattatagca 19260 aatcacagtc ccactagtga tgttggagag tatcattttc ctcactagta ctcctatttc 19320 cctgctttct aatctttcct gatctaatga gtaagcattg ttaattttct tttcattttc 19380 ttgacttcta atgagcttaa gcatcttttc acattattgt tgttcctttg gattttctta 19440 tctgtcaatt accaatggat atccttgacc tatttctccc ttatatggtt gcttttctct 19500 tattaaaaat ttgtaaaagt tctttgacta ttacagattt taaaaactgg cagataaagt 19560 tgtatgattt attgtgtata atatgatatt ttgagatata catatatctt gatatatcaa 19620 tatcgagata tatatatcac acgttgtgga atggctaaat atagctaatt aacatgtgcg 19680 ttacctcatg aagttatcat ttttgtggtg agaacactta aaacctctca gcatttttca 19740 agaatataat atattgttat taactatagt caccatgttg tacagtggat ctcttgcact 19800 tacttttccg atttaactga agttttgcat cctttgacca atgtctttcc aaccctcacc 19860 tcccacccct ctgcccgaca ctgccccagc cccggtaacc accattctac tctctatgtc 19920 tatgagatca acctttttag actctacata taagtgagat cttttggtat ttgtctttct 19980 gtgcctggct tatttcactt aatataatgt gctccaggtt catccgtgtt gttgcaaatg 20040 acaatatttt tctctttttt taaggctgaa tggtattcca ctgtgaacat ataccatatt 20100 ttctttatcc attcatctgt tgatggatac ttagattgat tctacatctt ggctattatg 20160 aataatgctg taataaacat gggagtgcag atatggcttt gacatactga atacattcgc 20220 tttgggcata tacccagtag tgggactgct gagtcattcg gtaattgtat gattactgtt 20280 ttccatagtg gctgtactaa cataccttcc cactaacagt gtgcaagggt tctctttact 20340 ccgcatcctt gccaacactt ttaatctttt gtccttttca taatacccat tctaacaggt 20400 gtgagatgat atctctttgt ggttttaatt tccattttct gatgattata gtgatgctga 20460 gcattttttc tatagatttt ttttttttgg tcagtggatt gctaaatctt accccgtcaa 20520 taatttctcc tttgatttta cttttataat tttctgctac aaaattaaaa aataattgta 20580 tgaaataaaa tttttcttcc tatacgtatt ctgaatttcc tatcttactt caaagagtct 20640 tcccacctcc tattttctaa aattttcttc taaaaatttc tatgttttat tttattattt 20700 ttaatattta gtatttttta catctggaat ttttttatat aaaagtggaa ggctcaactg 20760 catctctttt tatataaaga acgaattgtt taaacatcac atgttaaata atcttttctc 20820 caataaatta aattatatta gcatcaattt aaagattttt tttctctaaa ccactaatct 20880 atttatttgt tgccaggcct gagacgtatt gctttgatta taatagctgt atagtctctt 20940 ttaacatttg gcaagtttga tgctccctac tcattaatat tatttataat gttagcctgg 21000 ttttcctttt tttttttcag tccaaatagg atttagtcag aagaaagata cgtggattac 21060 atttttaaaa tactgatcaa aatgaagatg ctccaaccgt ataaatggca gatgaaatag 21120 actttaaagt aaaaaatatt tatcacacaa tatatcagaa aaatataaca aacccgaacc 21180 aacaaacatc agcaacgtag ctccaaaata ttagcttgaa acatgaaatt gccaatagtt 21240 gaccactttt tgacctacaa aagcaacaat ttatataaag aaaaggtcaa taaaattatg 21300 gtaaattgaa ttttttttta ttattacact ttaagttctg tgatacatgt gcagaacgtg 21360 caggtttgtt acacaggtat acacatgcca tggtggtttg ctgcacccat caacccgtca 21420 tctacattaa gtatttctcc tattgctatc cctcccctag ccccccaccc tctgacaggc 21480 cccagtgtgt gatgttcccc tccctgtgtc cttaggttcc cacttatgag tgtggcgttt 21540 ggtttgatgt tcctgtgtta gtttgctgag aatgatgatt gccagcttca tccatgtccc 21600 tacaaaggac atgaactcat cctttttaat ggctgcatag tattccatgg tgtatatgtg 21660 ccacattttc ttaatccagt ctatcattga tgggcatttg ggttggttcc aagtctttgc 21720 tattgtgaat aatgctgcaa taaacataca tgtgcatgtg tctttatagt agaatgactt 21780 ataatccttt gggtatatac ccagtaatgg gattgctggg tcaaacggta tttctagttc 21840 tagatccttg agaaattgcc acactgtctt ccacaatggt tgaactaatt tacactccca 21900 ccaacagtgt aaaagcattc ttatttctcc acatcctccc cagcatctgt tgtttcctga 21960 cttttttttt ttttttgaga tggagtctca ctctgttgcc caggctggag tgcagtggtg 22020 caatcttggc tcactgcaag ctccacctcc cgggttcatg ccattctcct gcttcagcct 22080 cccaagtagc tgggactaca ggcgcccgcc atcatgccca gctaattttt tgtattttta 22140 gtagagacgg ggtttcactg tgttagccag gatggtctcg atcttctgac ctcgtgatcc 22200 acctgccttg gcctcccaaa gtgctaggat tacaggcgtg agccaccgca cctggcctgt 22260 ttccagactt tttaatgatc accattctaa ctggtgtgag atggtatctc attgtggttt 22320 tgatttgcat ttctctaatg accagtgatg atgagctttt tttcatatgt ttgttggccg 22380 cataaatgac ttcctttgag aagtgtctgt tcatatcctt cacccacttt ttgatggggt 22440 tgtttgtttt cttgtatatt tgtttaagtt cttgtagata ttagcccttt gtcagatgga 22500 gagattacga aatttttccc ccattctgta ggttgcctgt tcatgctgat gatagtttct 22560 tttgctatgc agaagctgtt tagtttaatt agatcccatt cgtcaatttt gccttttgtt 22620 gccattgctt ttggtgtttt agtcatgaag tctttgtcca tgcctgtgtc ctaaatggta 22680 ttgcgttggt tttcttctag ggtttttatg gtttcgggtc ttacatttaa gtttttaatc 22740 ttgagttaat ttttgtataa ggtgtaagga agggatccag tttcagtttt ctgcatatgg 22800 ctcgccagtt ttcccatcac catttattaa atagggaatc ctttccccat tgcttgtttt 22860 tgtcaggttt gccaaagatc agatggttgt agatgtgtgg cgttatttct gaggcctctg 22920 ttctgttcca ctggtttata tatctgtttt ggtaccagta ccatgctgtt ttggttaccg 22980 tagccttgta gtatagtttg aagttaggta gcatgatccc tccagctttc ttttagcata 23040 ggattttctt ggctatacgg gctttttttt ggttccatat gaaatttaaa gtagtttttt 23100 ctaattctat gaagaaagtc aatggtagcc tgatggggat agcattgaat ctattaatta 23160 cttttggcag tgtggccatt ttcatgatat tgattcttcc tatccaagag catcgaatgt 23220 ttttccattt ctttgtgtcc tctcgttttt ccttgagcag tggtttgtag ttctccttga 23280 agaggtcctt cacttccctt gtaagttgtc ttcctacatg ttttattctc tttgtagcaa 23340 ttgtgaatgg aagtgcactc atgatttggc tctctgtttg ttattactgt ataggaattc 23400 ttgtgatttt tgcacattga ttttgtatcc tgagactttg ctgaagttgc ttttcagatt 23460 aaggagattt tgggttgaga tgatggggtt ttctaaatat acaatcatgt catctgcaaa 23520 cagagacaat ttaacttcct ctcttcctat ttgaataccc tcaatttctt tcttttgcct 23580 gattgccctg gccagaactt ccaatactat gttgaatagg agtggtgaaa gaggatatcc 23640 ttgtctggtg ctggttttca aagggaattc ttccagcttt tgcccattca gtatagtatt 23700 agctgtgggc ttgtcatgaa tatctcttat tattttgagg tatgttccat caatgcctac 23760 tttgttgaga gtttttagca cgaaggggtg ttgaatttta ttgaaggcct ttttttcatc 23820 tattgagata atcatgtggt ttttgtcatt ggttctgttt atgtgatgga ttacatttac 23880 tgatttgtgt atgttgaacc agccttgcat cccagggatg aagctgactt gattgtggtg 23940 gacaagcttt ttgatgtgct gctgggttca gtttgccagt attttatcga ggatttttgc 24000 atcaatgttc atcagagata ttggcctgaa attttctttt tttgttgtgt ctctgccaag 24060 ttttggtatc aggatgatgc tggcctcata aaatgagtta gggaggagtc cctctttttc 24120 tattgtttgg aataatttca gaaggaatgg taccagctcc tctttgtacc tctggtagaa 24180 ttcggatgtg aatccatctt gtcctgggct ttttttggtt ggtaggctat taattcctgc 24240 ctcaatttca gaacttgtta ttggtctgtt cagggatttg acttcttcct ggtttagtct 24300 tgggagggcg tatgtgtcca ggaatttatc catttcttct ggattttcta gtttatttgc 24360 gcagaggtgt ttatagtatt ctctgatggt agtttgtatt tctgtgggat tgctggtgat 24420 attcccttta tcatatttta gtgtgtctat ttgatttttc tcttttcttc tttattagtc 24480 tggctagcag tctatctatt ttgttaatct tttcaaaaaa ccagctcctg tgttcattga 24540 tttttttttg aagtttattt tgtgtctctg tctccttcag ttctgctctg atcttagtta 24600 tttcttgtct tctgctagct tttgaatgtg tttgctcttg cttctctagt tcttttaatt 24660 gtgatgttag ggtgtcagtt tgagatcttt cctgctttct cttgtgggca tttagtgcta 24720 taaatttccc tctaaacact gctttagctg tgtcccagag attctggtat gttctgtctt 24780 tgttctcatt ggtttcaaag aacttattta tttctgcctt aattctgtca tttacacagt 24840 agtcattcag gagcaggtta ttcactttcc atgtagttgt gcagttttga gtgagtttct 24900 taatcctgag ttctaatttg attgcagtgt ggtctgagag actgttagga tttccattct 24960 tttgcatttg ctgaggagtg ttttacttct aattatgtgg tcaattttag aataagtgtg 25020 atgtggtgct aagaagaatg tatgttctct tggtttgggg tggagacttc tatagatgtc 25080 tattaggtct gcttggtcca gaggtgagtt caagtcctga atatccttgt taattttctg 25140 tctcattgat ctgtttaata ttgacagtgg ggtgttaaag tctcccgcta ttattgtgtg 25200 agaatctaag tctctttgta ggtctctaag aacttgcttt atgaatctgg gtgctgctgt 25260 attgggtgca tatatattta ggatagttag ctcttctcgt tgcattgata cctttaccat 25320 tatgtaatgc ccttctttgt cttttttgat ctttgttggt ttaaagtctg ttttatcaga 25380 gactaggact gcaacccctg cttttttttt gctctccatt tgcttggtaa atcttccgcc 25440 attcctttat tttgagccta tgtgtatctt tgcatgtgat atgggtctcc tgaatacagc 25500 acaccaatgg gtcttgactc tttatccagt ttgccagtct gtgtctttta actggggcat 25560 ttaacctgtt tacatttaag attaatattt ttatgtgtga atttgatcct gtcattatga 25620 tgctagctgg ttattttgcc cattagttga tgcagtttct cgtagtgttg atggtcttta 25680 caatttggta tgtttttgca gtggttggta ccagttttac ctttccatat ttagtgtttc 25740 ttttaggagc tcttgtaagg caggcctggt ggtgagaaaa tctctcagca tttgcttgtc 25800 tgtaaaggat cttatttctc tttcacttat gaagcttagt ttggctggat atgaaattct 25860 aggttaaaaa ttcttttctt taagaatgtt gaatattggc ccccactctc ttctggcttg 25920 caaggtttct gcagagtgat ccactgttag tctgatgggc ttccctttgt gggtaacacg 25980 acctttctct ctggctgcac ttaacatttt ttccttcatt tcaaccttgg tgaatctgac 26040 aattatgtgt cttggggttg ctcttctcga gagtatcttt gtgatgttct ctgtatttcc 26100 tgaatttgaa tgttggcctg tcttgctagg ttggggaagt tctcctggat aatatcctga 26160 aaagtgtttt ccaacttggt tccattcttt ctgtcacttt caggtacatc atcaaatata 26220 ggtttggtct tttcacatag tcccatattt cttggaggct ttgttcattc cttttcactc 26280 tttcttctct aatcttgtct tcatgcttta tttcaagttg atcttcaatc tctgatatcc 26340 tttcttttgc ttgattgatt cagctattga tacttgtgta tgcttcataa agttcttgtg 26400 ctgtgtttct cagctccatc aggtcattta tgttctgctc taaactggtt attgtagtta 26460 gcaattcctc tatccttttt tcaaggttct tagcttcctt gccttgggtt agaacatgct 26520 tcttcagctc agaggagttt gttattactc accttctgaa gccggcttct gtcaattcat 26580 caaactcatt ctccatccaa ttttgttccc ttgctggcaa ggagttgtga tcctttggag 26640 gagaagaggt gttttggttt ttggaattgt cagccttttt gtactggttt attctcatct 26700 tcatggattt atctaccttt ggtctttgat gttggtgacc tttggatggg gtttctgtgt 26760 ggatgtcctt tttgttgata ttaatgctat tcctttctgt ttgttagttt tccttctaac 26820 agtcaggccc ctctgctgca ggtctgctgg agtttgctgg aggtctactc caaaccctgt 26880 ttgtctgggt atggaggctg caaaacagca aagattgctg cctgttcctt cctctggaag 26940 ctttgtccca gaggggcacc caccagatgc cagccagagc tctcctgtat gaggtgtctg 27000 tcaacccctg ctgggaggtg tctcccagtc aggaggcaca ggagtctggg acccacttga 27060 gcaggtagtc tgtcccttag cagagctcaa atattgtgct gggggatccg tttctctctt 27120 cagagccagc aggcaggaat gtttaaatct gctgaagctg tgctcacagc cgccgcttcc 27180 cccaggtgct ctgtcccagg gagatgggag ttttatctat aagcccctga ctgggactgc 27240 tgcctttctt tcagtgatgc ccttcccaga gagcaggaat ctagagagac agtctggcta 27300 cagcagcttt gctgagctgc gatgtgcttc acccagtttg aacttcctgg tggctttgtt 27360 tacactgtga caggaaaact gcctactcaa gcctcagtaa tggcggatgc ccctcccccc 27420 accaagcttg agcatcccag gtcaagttct gactgctgtg ctggcagcga gaatttcaag 27480 ctcatggatc ttagcttgct gggctctgtg ggggtgggat ccactgagct agaacattgg 27540 ctccctggct tcagccccct tttctgggga gtgaatggtt ctgtctcgct ggcattccag 27600 gagccactag ggtatgaaaa acaaaaactc ctgtagctag ttcggtgtct gaccaaatgg 27660 ctgcccagtt tttgcttgaa acccagggcc ctggaggcat aggcacccaa gggagtctcc 27720 tggtctgcac ccaagggaat ctcctggtct gtgtgtttca aagaccatgg gaaaagtgta 27780 gtatctgggc aggagtgcac cgttccttag ggcacagtcc ctcagggctt cccttggcta 27840 ggggagggag ttccctgacc ccttgggatt cccaggtgag gcgatgcccc accctgcttt 27900 ggctcaccct ctgtgggctg cacccactgt ctaaccagtc ccaatgagat gagctgggta 27960 cctcagttgg aaatgcagaa atcacctgtc ttctgcgtta atctcactgg gagctgcaga 28020 ctggagctgt tcctatttgg ccatcttgcc ccttggtctg gttttcaacc ttcagtcttc 28080 catatttatt ttgaatgaat tttctgcagc tttattaaaa aagaatagaa acaagtaaga 28140 gcaaagcata gttggtttat ggttgtaata aacttatatg tatgtcctaa tgatttgaca 28200 gctttgtgat agtatcttgt aatccaagta catgatatat ttctacatta tttagatctt 28260 gtgttaggtt tttccataag attaattttc ttcatattgg ctttcttgct atgtttcttt 28320 ttagcataaa gctaatccag gaaaaggaat aaaactggaa ggaaaaaatg tcttaaacca 28380 ttaatattgg ctgaccccgg tggtagggtt atgaatgaaa catttttgct tcttccactt 28440 ttttatattt tccaaattgt ccatattaat catgtatgat ttttataata ataaattaat 28500 gaaatttaag aattagataa ttgattgaat tggataattg aattaataaa atttaagaat 28560 gagaatagga ataattgtgc tttgaaaagt catatacaca agagttttag atggaattca 28620 atactaaatt tatatgctat actaaatcag taattctcaa ggagcaaagg tgctggggag 28680 tgtggaggag ctctttgttg gtgttgcaca tacaatttaa gacaacattt tccttattcc 28740 tcaccatttt aaccatatca cctaaccagc ctctggtagc actcaataga catctgatga 28800 atgaatgaat aagtgaatga aaacattgtg acaaaatggt ataacatttt gtatttgaaa 28860 aatatatgaa aatctattct tttcaaatat aaaatgggaa aataaaattc aataaaaata 28920 tcttggttgg tgagaataca caaaagatat accttcttgt ctatgaatta gtaataagaa 28980 attgtcttga ggaagtcaac tacatctgga aggttctctc tggacaagga gcataagtga 29040 aaaacagtgc actaaattat aaccaagagt tgcaacttac cattttaatg cttcagcaca 29100 ggcacagaga ctaacattta ctaagcaaac aagaagtctt ggcaagttaa ttaaataatg 29160 aattattttt ggtgaccaag gagttgggct tctcatttta aaaccatgca tgagattttt 29220 ccctttctac ccattactaa aatatcgtat tagtgtgaaa aattatacca ggactgggag 29280 aaaaagaaat cacatctgtc cttgacaatg ggctgaatga agaggtgaag gagtggtttt 29340 actatctaag tgactgaaaa ataggttatg gtgccccagc aaatccttgt tgtttgctga 29400 caattagtga tgtctgttta aatcatgcag ttttattagg ccttaaaaat atcttttagt 29460 tagtttcaat ttcatcaagg gaaaaggaga gcagagtaga gtggaactct gctcagagtc 29520 cggttggaag ccttcaactt tgttctccct gttttcagat gagtgtctat ttgtggctct 29580 accttttctc tttcttctct taccatgaca ctcccctctt ctctcttatc ttagctgttc 29640 ttttcttctt ccgcatatta ggcagtggga gaaacaccct aaatcagttg gaggtgagga 29700 aagaagaaaa gcacccctat cttggtagtt cctcattctt cccttcgtca cgtccatgtc 29760 atcaggctct gccttcatct gcgatctgga tacaatccaa tttatagcat ccattcaacc 29820 aaaaaatatt gagctcttac tatgtcaaag tagtgttctg gatgctcggc tccatcagta 29880 aacaacctag actaacatct tgccgttgtt tacatctcgt ggtgtagagt ttacaccttg 29940 tggtctagaa tttacatctt gtggtggagg caggcagatg attaacaata aacttaagta 30000 ggtctagatg tcaaaaggtg gtaaatgcta caggaaagag caaaggtcga gccaggtaag 30060 gcagattggc tgtgtgggtg tggaggaagg gtgcaagagt actgtcaaga taagccttcc 30120 tgagaacatc tgaaccagga catgaaggac atgaggaagt gagacagtcg ctatccaggg 30180 aaggaatttc caggcagaag aaagagccag tgttacgcct taaggtggga gcatttctgc 30240 gagactggag aatcactgga gtccattgta cttggagccc agcaagggag aaaagattgg 30300 aggactcagg aggtgctggg gcaggtgaac tgctttttga ttggggagtt cagagggtaa 30360 tgctttggat aaatgtaact gaaaactttc tcagaagtgt tttcatacta tctctacaat 30420 tcattttcat gtgaaaactt aattggcgag cagattaata tggtgatctt cccttagatc 30480 actaggaaaa tcttgtttta tgaatttttc ttcccttttc attcactagc agagaaaaga 30540 gttgtaaagg agccgcagaa aattatagta ggtttctccc tactactgag ctactgagac 30600 tggaagatgc tcacgttagc aactgagtat atttatgtat ttccctttaa tgtttgaagg 30660 gtcaggaata tttgacttag gatactagtc tgtttagaaa catgattcaa ctagctacat 30720 gactaaacta gcagctgtca gagagaatgc aaggtcaaaa cttagtagtt gataataata 30780 aagaaagggc agagtgttat gaaatgttat gatctgggta atccattggc tcactttttt 30840 ttgtcagcct aaggttacaa gatgataaat taagttgcta atattctata tctaccattt 30900 acttttcctt tatcatgtgt ctggcaatat gctgagtgtt ctacctctag cattttattc 30960 aaactgtgca atctgcctgc tgaaacaagt atcattaact tcatttccta aggtgagaaa 31020 attgaggccc agagaggtta aataagttta ggatcatatg catagctggt aagtactata 31080 ctttaatatc cctttgcctt catgctttgc tctcactcca tgtttaaatg agcagagaga 31140 cttatcttta aacagatata tagcaagtag tattttccaa atgaattcca caagatgctc 31200 cattgcaaaa gttcaaataa gtttagaaaa atgctgcaaa ctttgtgctt cttaagagat 31260 ttacagtgca gattagcaca ttaaagcctt tgggaaattt gtattagaaa aacctttatt 31320 aacttattta ccccaatttt tccaagcttt ttgatcacga aactctttaa aaaacaacaa 31380 gtataattgc ttttatagta ttctttggga tacacttgga gaagtgttac atgaaaagat 31440 atgattggat aaatttaaat ataggaagaa ttatttaatc attttttgga ataaaacacc 31500 aattttaggt tgtctaacat acatttgagc caagacatga aggacatgag gacataattt 31560 acttttgtcc ttgtaaggac ataatgcact tttagtggtt tgcattgttt attttctttt 31620 gaatttcatg ttactttata aaggtaatta tttaatcaaa ccatttgtta agtgtcagac 31680 actatggtag gtgctggtaa tataaagaga atatgtaaac atcaacacaa catatctcct 31740 agtatgggct tacagtacag tgagagacac aaacaaataa tttgtaggat tgaaataagt 31800 cttacatttg ccacatcaat aaagcactat ggaaacaaag gcacaagaac ttaactttgt 31860 ccaatgaagt ctttcaggag gaggtgatat tggagctgaa ttttaaagga ttcatagatg 31920 tttatctgaa ggactaatgc aacatgttgg aggtgagtct tcaggaaaga ggcaacaaga 31980 accatttggg taacaagata ggacttggca agttagggga gtcgtaagtg gttcattacg 32040 gctagaatcc agggctctct ggagagattg ggagtacaca gatcactcaa gggtttggta 32100 tgaactgtca ggctactaag acagaaataa caaaaatcag atgtgggttt agaaagagca 32160 ttttggctgt aatacagaac atgatggata attgatggag cgagattcct ggggagatag 32220 aagaggatag ggccatgtaa gtacatctgc tggtatttta aaattagaaa aagaaatttt 32280 tggtagcaaa atcagaacag acccaccaac tctttgcaaa tcatgggact agaatgtttg 32340 gaaaggaaga tgctaacgat tttcattcat ttgtttatca tctatgttga gtgtcttctt 32400 gggcctaggc agcatgccca aagctgggag aataagatac tgtatgagat gctagaaaga 32460 tccccacctc tcctttccag aaattcagta tatcagacta attggtttac agttgtgacc 32520 atgggctttt ggcatagctg ttcaacaaga tttcattctt tttcaaaagc aattcattca 32580 tccaccaaat atttgttaaa caaatgtacg ttgcattgta gtgggtcctc agggagctgg 32640 atgtacatgc caaatatgtt tcattttatt tgaagcaagt ccacagacaa gtaaactagt 32700 caagtgatac caggcaaagt gatttgcttt ccaacagatg gtgacagatt aatttcctaa 32760 gagactgatc tgccccagag gcactgggaa agtcttgtta gggaggtaga ttatagtcag 32820 gaccttggaa aattgttggg aataattgag gtcaggaagg gtatacttag gtggatgggg 32880 acagcccctg aacgagggat cagtcctttt ggagtgagca cggaatattc aggtgcctgg 32940 gaggagtgaa ggcttgtgct tcagcactga ttgtgtgcac cgatggtgga acatacctgc 33000 ctgctcagaa gctttggctt ctctctgtag gtgagagaca gccattagaa gtccttgaac 33060 agggaagaaa cacggtgaaa gcaaggattt cattgagaag tccctcatgg aagaagaaga 33120 ttacattgga aagagcctgg cttagggagg gagcagtgac aatcagagaa aaaggcagat 33180 aggggcaaag atactggaag aagaggaaaa actgtccaaa gctttgtcct tgtgtgggaa 33240 agctggtgct gttggcgtga aagaggaagc aagaacatgt gcactgacac ggctgagagt 33300 ctccaaaacc attgtctttc cttaaaacag taatgatcac aagcagctta caactttgca 33360 tatagccact ggggcaaaat cctattaaaa gctaattcat tatctgagcc agtgcatgat 33420 aatgcgatgt aaaggcgtgt tgggaggcag atgatcagaa cttttaagca aactaaattt 33480 cataacattt attagaagcc tgtctctatt tccagaaaac gcctataaat gtggctgtaa 33540 tgtaggctac aggtcatcac actgaagtag aagcaatgta caatacctga aaggttagag 33600 aagttcaggg tctgggctta taaaaaactt cattattcat ttgaaagata ttgttttgta 33660 tcccccaatt gtggttttca atgtatataa aagcaggata tcatactttt tgatctatgg 33720 atttggaagg ggataatggt gtggtgggca ctgagcatat ggaattattt aattagagag 33780 atgcccttta gattactata aaatataacc agaatctcct gtttagactt ctaaaatcta 33840 cttctttgaa aacactacta aaatgaccac aaagacctgt cctcacaagt gggagctatt 33900 aatcaatagt gtgtacacat ggacatagag agcagaataa taaacactgg agactctgag 33960 gggtgggagg ggaagaggga ggtgagggat gagaaattac ttgatgggta caatctacac 34020 tattctggtg attgatttct ctctgtttcc tcttcagaaa ctgagaggaa atttagtttc 34080 ctcagtcacc actcctccaa actcctgcgt gggtgataca agacttgctg tcatcttgag 34140 gcagaagggg ttaggggatt tccccattga acctgatagc cttcatttca tttctgtctt 34200 ctcagggaaa catttacccc tctttactaa atggaagaag gtttgtaaac taggagggta 34260 tctatggatc tgattgctcc ttcaccactc tgctatatat ccatgtaaca aaacagcgct 34320 tgtggccgga tacagtggct cacacctgta atcccagcac tttgggaggc cgaggtggtc 34380 ggatcacctg aggtcaggag ttcgagacca gtctggccaa tacggtgaaa ccctgtctct 34440 actaaaaata caaaaattag ctgggcgtgg tggagcattc ctgtaatcct tagctactcg 34500 ggaggctgag gcaggagaat cgcttgaacc cgggaggccg aggttgcagt gagccgagat 34560 catgccactg cactccagcc tgggtgacag agcaagactc catcgtggga aaacaaacaa 34620 acaaaagaac agtgctggta ccccctaaat ctataaaatt ttctaaaaaa taaaatgaca 34680 ataaaggaat gaaaaaggca taggtacaag cagatgggat aggacactaa agcaagctgg 34740 agtaatactg gaattctaga aggtagaagg cttagcagag cagttcaggt ggaacccacg 34800 cctgtggggg caggggcatg agcagtgagc ccatctaact acgggacccc agataggctt 34860 gggatctaga agcgacagat gcctctaaag gctgggggta ggctgggact gaaagcagaa 34920 ttggtgtaaa gtctttaaaa ggagcaatta gatccacaaa taccttccta gtttctaatt 34980 attctaccgc ttaggagaga ggggtaaatg actccctgaa aacagagaaa tgaagtgaag 35040 gctatcatgt taaatgggga caacacctag cccctccttc ctcaagactg acaggaaagc 35100 tcctacaacc cacgaaggag tttggagggg tgttgtctga ggaaactaat aagtccaaga 35160 gaaagaacct tcagaaacgg acatttaaag gattaggtcc ccacccgatt accctagaga 35220 tacacataca gaaatgtgat tggacagtca aggatcaccg tatgatgctt ctaacctgaa 35280 caatagacac ctagtcacac acccaaacaa tcacacacac acatacacac acacacacac 35340 acacttactt cacttctgct ggaggaattt acaagatgaa gaacatcttg tatctctttt 35400 gggctactgt ttgtgaaagg aatggttgca tgtgctcttg gctaagccaa ctccatcctg 35460 aagacagatt tttgtgaggt gggggaaatt cgcccagcgt taatagtgtt agtggttgtc 35520 ctgggtccat cctggtctgt attcctgctt tttcattttc agatttaaat ccagagttat 35580 tacagatggt aacatctgat gccaatttat ggatcttttt cataattcac ctgctaggaa 35640 tctcaggtaa cctataaaat atgcttttat ttggtcattt taagagttac gtttctgaat 35700 ttcaggtatt ttatcctgta ttgtcagcac attaaattag ggaacacatt cattgacatt 35760 ctatgtattt tcctttgtat ttcaaagtca gagtcaagta tttaaaaaga taagatcttt 35820 cattttgtgt gtgatcccac ggaatacttt ctactgtaga tttattaaaa ttctcccacc 35880 tctggcctct gattaaggaa ttgcagagta ttctctatga caactcatta aacctattat 35940 tccccccagg gcggtttagt atatcactaa atatactttt agtgatattt gttgattgga 36000 gcatagcttt tgtgtttgcc aaacatcatt gatgtgtttt gaggtcatgt ggttgtgggg 36060 ggcagggggt ggttgtaaat gtaatagtgt ccctctagta ttgtaatact tcaaggacat 36120 agaatttatt ttttaaagtc ttaaatcttt ttgtttgttt ttctaggaaa tcttgagtct 36180 atgttctttg atttgagact atagagtttc ttggtaaagt ctccaattat tggttttctg 36240 agtaaattct tgagaattgg tgaggctccc aggattattg tttgtcatcc tgttctaatt 36300 aatagagaaa aagcatataa atcttagatg tcttagatct gggactattg catctacttg 36360 gcttgagcca aagtgtcatc taatttttat ccagtaattg tggcaacata ttgcttccaa 36420 aacaaatcac atttgtaaat gcatattgag cattttctac atgaagggca ttaccaggga 36480 gtgaaagaaa tataaggtct gaattttgtc ctctgggaga gaacattcta gtgggagaga 36540 tgagttgtga aaagttaaat aacaaatatt tatagatggt caatatagga acttgcaaat 36600 attattaaga ttaattacat gtgaaaaatt gttattgaat tcaaggcaaa agaagtgaac 36660 ttaaactgag ttgcacagga agaactcata aaaaggtgag cttgtgttgg atgagtggat 36720 ttgggcagat aaagaaagac aggagcaaaa ataaagaggt ggaaaaccac aggggtgttt 36780 gatgtatgca gggcacggaa atcagttgta tggtgggggg taccttcaac ttaaaacctc 36840 tgtaccagtt agggtgcttg agttgtaaga agccgaaacc aattctggct catttaggcg 36900 gagaaagaat ttacaatcca tgactaggat atatccctcc atctatttaa tccctgttta 36960 acttttcttt attttttata gtttgtatag ttttctatgc agaagacttg cacatctttc 37020 gttacatttg ttcataagta tttgacactt ttatgttatt attaaagatt ttcttttttt 37080 ttttttgaga cggagtctca ctctgtcgcc caggctggag tgcagtggcg caatctcggc 37140 tcactgcaag ctccgcctgc cgggttcaca ccattctcct gcctcagcct cccgagtagc 37200 tgggactaca ggcgcctgcc accacttccg gctaattttt gtgtgtgtgt ttttagtaga 37260 gacggggttt caccgtatta gccaggatgg tcttgatctc ctgatttcgt gatccaaccg 37320 cctcggcctc ccaaagtgct gggattacag gcgcaagcca cagcgcccgg tcaagagttt 37380 taaaaaaatt tcagtttcta actgttgaca ctacatagaa atacaataga tttttgcata 37440 ttgtccatgt atctgccaaa cttgctaatt taacttatta attataataa ttttatctat 37500 ggattctttt ggattttcca aatatacaac atgccatata tgagtagtga catttttatt 37560 tcttcttcct agctccgtaa ctttattcta ttttcttgac ctactgcatt gactaggatc 37620 cttcactaca atgggaagaa aaagtgatgg tgggcattct tttctcactc ctgatcgcag 37680 ggcagcattt aacttttcac cattatgaat gatgtttgct ctacagattt ctgtagaacc 37740 atttatcaga ttcaggtagt taatcctaac ttggctaaca gcaattaaaa aaatgaagta 37800 atataaaaat taagaaatta atatgctgct aatgatatgt tgttgagtaa cataaatata 37860 ccaatttttc tatatctact gagatgatca tatgaatatt gttctttatt tactatggtg 37920 aattgcattc attaattttc ttttcttttt ttttttgaga cagagtcttg ctctgtcacc 37980 caggctggag tgcagtggtg cagtctgagt tcactgtaac cttcacctcc tgggtccaag 38040 tgattctcct gcctcagtct cccgagtagc tgggattata ggtgtgcacc atcacgcccg 38100 gctaattttt atatttttag tagagatggg gtttccccat gttggccagg ctgatcttga 38160 actcctgacg tcaagtgatc tgcctgtctc ggcctcccaa agtgctggga ttacaggtgt 38220 gagccactat gcctggctgg attcattaat tttcaaatgc attttaaaat ttctgaacta 38280 aatccaactt gattataata tactatcttt ttttaaggga aaagtagatg aatcagactc 38340 agcaaaaata ggagccagaa tagcaactga tacggtttgt ctatattccc acccaaatct 38400 catcttgaat tgtaatctcc ataaccccca cttgtctagg gagagatctg gtgggaggtg 38460 atgggatcat ggtggcagtt tccctcttgc tgttctcgtg atagtgaatt ctcatgagat 38520 ctgatagttt tataagggcc tcttccccct tcgctactca ctctgtctct cacctgccac 38580 catgtaagac gtgccttggc tactcctttg ccatctgcca taattatctg agatctcccc 38640 agccatttgg aactgtgagt cagttaaacc tcttttcttt ataaattacc cagtctcagg 38700 cagttcttca tagcagcgtg aaaattaact aatacagcaa ccatggcagg ggaaggccaa 38760 gcaccttgac tgagtatatc caatgggaga ggagattttt ttctcacagc caaatcagga 38820 cactcacagc tttgtgttta aaagcttggg ctctggactc aggctgcctg gtttgaagtg 38880 ccagtcctcc ctcttatgtg gcaggggacc ttagctctga gtatccttct ctataaagga 38940 ggatgatgtt ctatttaccc aataagattc taaggattaa atgatacatt aaagtgcaca 39000 ggtcagatca ctctcagccc atagaagtaa ttataattcc agctattatt attgttattt 39060 gtgaatatga gaaagaagaa agttcactct gacatcctgt aaatggaaaa ttcaactgaa 39120 cattgaaaaa tgtttaaatc tgtctatcag aaagtttttc atcaaaagaa aacactgagt 39180 agtctagtgt tgtagcttga tccaaaacct tgaataattt tcaaactcat ttatgatatc 39240 tgaaatattc aatgacttat acctttgaat tttttggcag ctttgtggag gtatagctga 39300 catataagaa actgcagata ttcaaaatgt acagttttat aagttttgat gtatgtatac 39360 aaccattaaa ccactaccac aataacataa ggaacatacc tgccccccat ccacacattt 39420 gatgcgcctc cttttaaaat tctctttcct accctccacc cctcactgtt taccaaaaag 39480 aatgtctgat ggtgccctgg gcagtcccac tctgcctaga aaacaccata gaaaaagaca 39540 gcaaaagtgc tttctcactc tggagttcta cttgatttta atggacatag attagtgtga 39600 accacataaa ccagtactaa aatacaggat ttgatctaga aaaggtgatg ctaaaaatgc 39660 atgtagataa aacctaattt ttttcagaca ccaaaatgaa aaattattag tatgccatga 39720 cacatgaaca cttttatatt ccacaaccac tgtgctctcc ttttggtgtt catttgcaat 39780 ggatggaatg tttatgtccc ttccaaattt gtatgttgaa atgctaactc tcaagatgat 39840 ggtattagga ggagaggctg ttgagaggtg attaggccat gagggtggaa ccctcaagaa 39900 aaggattagt gccctcagca aagaggccta ggagagctag cttgctcttc ccagcattta 39960 gggacacagc aagagggtgc cgtctgtgaa ctagaaagca ggccctcacc agataccaaa 40020 tttgccaatg ccttggcctt ggacttccca gcctccagaa ccatgagaag taaatttctg 40080 ttgtttataa gccacctagt ctatagtgtg ttttgtttta gcaggctgaa tggactaagg 40140 cattatttat tgtgagttct attcaccatg gagcatatgt ggcctatgtg tccctggcac 40200 tgaggcagga actgagcaga gtacgcaggg gaattaataa tgcttggacc tatctttaaa 40260 acacctagag tttagtagga atcaactgga agtagtaggg taaaggaaag taggtgactt 40320 ttgttgagcc ctgccatgtg ctagagactg tgctaaagtg atttacccac attatcttat 40380 ttgaacctca tggcaagcct gtgtggtagg tcctattcct ctatttacag atggggaaac 40440 tgaagctcag agacattaag taatttgccc aaggttatag aattatcagc aacaaagctg 40500 aaagtggcaa agggctcttt ctagtcagga ggaattaaga gagcttgggt gcagtggctc 40560 acatctgtaa tcctagcatt ttgggaggcc aaggtgggag gatcagttga gcccaggagt 40620 ttgagatcag cctgggcaac atagtgagac ttcgtctgta cagaaaaaaa gaaaaaagaa 40680 aaaaagagct tgggatcgtg cctcctgtga ctcagcatca ccttagtctt ggtctgcctc 40740 cattctgaat tgtgccctaa agctagtcat tgcttccttc ttggtttctg ctacaagttt 40800 ctgcctctcc cactggccca tttccggggt tcctgttcct gttatgcaca tcaatcccta 40860 gatttctgag gtcccagagg gtgggcttct gcttagtccc tgtttgtctt cccagggcta 40920 ggcatcctgg tccttagccc tggcactggg gcttctctcc ctgctgcctt cgaccccccg 40980 gggctgacca tctgctgctc tatccctgca tcctgccagc tttcacatcc cctgtctcga 41040 gctctgcttg ccctttactc ttgaggggaa ctccctgcct ccacctgttg gactggtctg 41100 gtcccttcac tggtcctgcc ctttctgacc atcttctact ctggtctggc ctcccatttt 41160 ccagagctca tctgtctcca tgtgtgtcct gcttctcaga gggtcttgag ttccagcttt 41220 tccaggtctg gctggtgcca tggccaaaac ctgtcccacc tctcccattc gagttcctca 41280 ctagctcctt tttgacagtt ctttcttttt tggggtctag ctttggcctt gctgcatgaa 41340 tcattaacac ataaatatgt gtcttcacaa ttaattgttt ccatttggtg tttgctctag 41400 tcaaggagga tggagaggga gcaacatctt gtactgaatg tcttgacatc actaggaact 41460 agactgcttg tgcttcccgg gcatgctgag gtctcaagaa taaagagtat ccctgaagac 41520 attcttatca gtcttccctg gtgaaacatt catcctaatt tttcctttta gctttgagac 41580 cacttttgca tgatttttaa tatgtcatta aattaaatag atataatttt ctctgtctag 41640 ccaagctgct gttagaagaa tctttgcata caactaatca taaaaaagac attcttcttg 41700 cctctttgga aaggagcctg tgtcacctaa gagtgaggag tacactcatt cttttgtgcc 41760 ttgttcatct gctcagggga ttattgatta gcagatagaa tgtgggtgca ggctggacgc 41820 agtggccatg tctgtaatcc agcactttgg gaggccgaga tgggtggatt acttgaggtc 41880 aggagtttga gaccagcttg tccaacatat agtgaaaccc ccgtgtctac taaaaatata 41940 aaattagctg ggcgtggtgg tgcatgcctg tagtcccagc tacttgggaa gctgaggcag 42000 gagaatcgct tgaactccgg aggtggaggt tgcagtgagc tgagatcgcg ccactgtaca 42060 ccagcctagg tgacacagtg agactccatc tctcaagaaa aaaaaaaaag aaatgtgggg 42120 gcagataagt tttttggggg gtttgctttt aattctttgg aagaactggg cttggctggc 42180 tgggcaccta gagcaatgtg gacatgggca gctgcttgtc ccatggatgc cagggacaga 42240 gtcacaagag agacggttag aaatggtgcc aggttctcgc tgcctcgtgc caggtcagct 42300 cccaacaaag cctttgtaca agacacatat aaaccctcag agagtttatg ctaacccagt 42360 gtcttggcca tggcttactc atgatggaaa actgatcata ttttattctg gccacatgga 42420 ataatagaca tgtaatcact atgagatttg agttgcaggg tctttggttt ctaataacct 42480 ttataatttt ctccctcatc agggagacag aataaggtgt ttacattact actttcattt 42540 tgcaagaata agatcgaggt taaatctaca gttatgtctt gatagactgc agcagatttc 42600 tgcatcagta gaaagtgctg ttttcccact aatcagaaga agaaagtgct agccataatg 42660 atatgggtcc actgtgaagt agaagacaag aaacagagca ggacgtggaa ttgggagcaa 42720 tgagaaaagg tgcctagagt tgctcttggc accctgcacc ttagatcacc cttattaact 42780 gcctgctgtt tactctgaaa atctttctgt catttttgag agataaaatc tgaaaatgca 42840 gtttcttcaa gttagaaatg ataattttta taatagagtt taagaaagcc atgcttcttt 42900 tctcttctat gagaacattt ttatttcaat tataaaattg ccactataaa tagccagtca 42960 agttcatagg gcatgagtct catcaggcgg ataatttaca ttatataaaa aaagtatgag 43020 ttatttaact aaactaaaaa agcaaccagt atcttgtggt cacatactgt atgtgatccc 43080 ttttacttgc aaggtaaaaa gtggtttcat aaccttgcca atataattcc aaagaactaa 43140 ggacttagtg atcgttgcta attgaagtta ttctgtttat gagcaagcaa cactatttct 43200 ttgatgaaaa ccagaaagga tttacgtgtc ggtaaatagg gttcctttat gtttgtgtat 43260 gtgtgtgtgt ttgtgtgtgt gtgtgtgtgt gtgtgatttt atgaggtttg tctcattctt 43320 ctatgctagt gagtgttgat tagttggatt gccttttcag ttgacctatt gctttttaag 43380 agcatttttg gatatagtcc cttaacccag aattaacttc tatgataaaa acgctttttg 43440 ggttgtcaga gaggctaata ggggatatat gggcagggag ttttttacca gccgtcagat 43500 ctcatcttgc agactgtaac tactgtaacc atgccccatg aagggtagta caaatcatgc 43560 tattgaaatt gagagagatg gctgcctttt ggacaggaag agaactagaa gtttttgact 43620 ttgtgaatct aacctctgca gctgcatccc ccagggctgc tgtccacata ccctgtgctc 43680 cactccctct catgatttct ctcaccaccg tcattctttg tttctcttgt tcctttatcc 43740 tgaagctctc aacctatgaa cctgtgaaaa gcccagataa cagtaacaga ttacatttat 43800 ttatggaaca tttattatag atggtgtcat tttctaagta ctttaaccat attgattcct 43860 ttaatctttg caatcatgca gtgaaacagg tgattctcat actcccattt tacagttgag 43920 gaaactgagg cactgagggg tgaaatgact tgtctgggac cacacagtac gtagtcgagc 43980 tagtatttgg acccagactg tctaactcaa gagcccaagt tattggccac catactctat 44040 agcacctcta acccagatca aatatacaca gcaccatcac atagtgaaat taatcagtgt 44100 catgtccatt ccctctgctt aattgtatgt ttcttgtgat gaggaacata agccatctcc 44160 aatgcctggg gccacacata gcagatgccc tataactatc atcattgtca tcgtcattct 44220 tatcttcctc ttcctcctca tcataatcta ctacatataa ggcaaatttg tgggtcaggc 44280 acacttcaca taaattagat ttaattctca caacaatctt acgaaatttg tgttgtcccc 44340 agtttatagt tgaaaagacc ttgcatttag gaagtggtaa aatgggaatt tgcgaccctg 44400 ccatttggtt ccagaatcct tcctcctaac cactctatac catatgctta attaagaaaa 44460 aaagaaacaa ataggtgaga aaaaacaatg atgtgaagaa ttttgctgcc cccagtatta 44520 ggattttttt tcttcttctt gctagactct agagggccca gatcctgtgg agctgtctct 44580 ctgaagggaa gggtcaggct gttcaccctg attttcctgg agtcacagat aaacttctgc 44640 cctccaccgg atgcctctat cttacacaat tattttcctt tacaaatttg gttgatgaca 44700 tattcacttg ggataattgg gttgtccctc ctactttgaa actgtgagag agttcactca 44760 atttccaact gcgtatgaag ctcttgagtc agattttttt gcctgtaaca cctcagctca 44820 caccagtgca gaaatggaag ttttaattgg ctgtaggatt gaagggttgg tttggtgcat 44880 ggtggtattt taagaaaggc aaagttttat ttaaatgagg aatattctcc ctgggttttt 44940 tgagttagct actgggccat gcaacaggcc tggctgcttg tgagaaaatg agaagggtga 45000 tcaagtacaa gaagatgcag ccaaagaagt ggacacaatc cacgtcaagt tccatcttct 45060 ttgtggcagc catgattctg aaggtcactg aagggtattt ttccctgagc tgtttttgga 45120 gcctgtgcca ctggcttcaa atgctgggtc ttggccacct cagttgctat aaaatatggt 45180 tatgagtgct tccgcttccc agcatctagc tgacaaagcc ccacttgtgc cttgctcagc 45240 cccacttcat tgctcctgcc ctctctgggg agagggactc accacctggg tgacaaggtt 45300 agggcttctt gctgcacttt ttggcatctt gctgctccct gtataagggc aaagctaacc 45360 tttttttttt cttttcattg agacagtctc tctctgtcac ccaggctgga gtgcagtggt 45420 gcgatctagg ctcactgcag cctctgcctc ctgggttcaa gtgattctcc tgcctcagcc 45480 tcccgagtag ctgggattac aggcttgaac caccatgcca ggctaatttt tgtattttag 45540 tagagatggg gtttcatcat gttggccagg ctagtctgga actcctgacc tcaaggaatc 45600 tgcctgcctc ggccttccaa agtgctggca ttactggcat gaaacaccac cccacctcca 45660 accttcaaaa gatttaaaaa aatgtgaaaa ctgaaatgaa gactagatac taatgaaaca 45720 ttggactcat tatgactttg ttaagtcatt ttgattttat taaaatcaaa cattaataaa 45780 gcagactgtg aataaataaa ttatattctt tggccatttc ttcattagac aaggatgcta 45840 tctttcatgg ctgtgttatt gtggggatgg ctgatagctc atagaaccaa tctaacatcc 45900 acagattttt ttcatagttc tggactaggt ttcttagcat aatgcgttgt tgtggtcctc 45960 atggtctgtt gttctctctt gccaaccttg tttcatcagt cccctgttgt cctgcagatt 46020 tttgaagcat tggaatccta gcaacagatt tctcatttaa gtaggatggt cctgatcact 46080 agtctcccac agagagttgg taaaaagttt tgttcttctt atcacccaca gaacttccct 46140 gaaacatttt ttgttgtgct tgctcagaaa ccataagctt agtagaaaaa tgcaccttgc 46200 ttgtgaatac acaatcaggt gtccaaatga gatggtcccc tcctagaaga taatatttcg 46260 gaagtcttgc ctcagtggga ggtacttggt tgtttgtttt tgtttttttt ttcatttcaa 46320 tagctttagg ggtacaagtg gcttttggtt acatgcatga attgtatagt gctgaagtct 46380 gggattttag tttacccatc actcgagtag tgtactctgt acccagggtc cttggatttt 46440 atgggcttgt ttttgtttgc ttttatgtta agatatgaat aatatgatat gctttggctc 46500 tgtgtcccca ctcaagtctt atctcgaatt gtaatcccca taatctccac acgtcaaggg 46560 aggtacctgg tgggaggtga ttggatcatg gggggcaatt cccccatgct gttgtcataa 46620 tagtgagtga gttatcatga cgtctgatgt ttttataagt gtttgaccat tccaccttca 46680 cacgctgtca ctctcacctg ccgccatgta agacatgcct cttccccttc tgccataatt 46740 gtaagtttcc tgaggccacc ccagccatgt ggaactgttg agtcaattaa acctctttcc 46800 tttataaatt acccagtctc gggtatttct ttatagcagt gtgaaaacag actagcatat 46860 aatagaaggc tctttacctt tttaaacttg gaaggccaaa ttaatactgt cctttccatt 46920 ataagaatct tcagattaaa tattttctca ttcattgtcc ctcagatcat atacatttgc 46980 tttttaactc taagttacat gtaataaaca atgaaattgt attgtggatc ataaacttga 47040 gttttaaaaa gatttttctc ctaattttaa aagtaataaa aacaataaat acttactgta 47100 ttccaggtag tgtttttttt tttttttgag atggagtttc actctgtagc ccaagctgta 47160 gtgtggtggc gtgatcttgg ctcactgcaa cctccacttc ccggcctcaa gcaattctcc 47220 tgcctcagcc tccttggtag ctgggactac aggcacaagc caccaagcct ggctaattgt 47280 tttgtacttt agtctctact aaacagggtt tccccatgtt gcccagggtg gtctcgaact 47340 cctgagctca ggtgatccac ccaccttggc ctcctaaagt gctggtatta caggcgtgag 47400 ccaccgcgcc tggcccaggt agtgttctaa ggggcatgct tccattaatt catggaattc 47460 acaataaccc tttgttgcag taactattat tatccccact ttacagatag gaaagcggta 47520 cagtgactgg ggcagagaga ggctctgtga ctttgtgcaa gcagcaatgt aggcatttga 47580 atttcggcac gctggctcct gagtccattc tactaaaaat tgtgctgtat ttaatgcaga 47640 gaatttcaaa aacatgagat aaaaaataag agaagaatag catcaatttt cccatcattc 47700 aaaggtatct gttaaaagga aacatttaaa acttagctat atatactttc tgaatttgta 47760 tgtacatata aacttataaa aaatgaaaat gctaattgtt ttcacacgta ctgtttggta 47820 gcctcccttt ggtatgttcc cagaccaaaa attattattc ttccccatgc tttttttcag 47880 ctacataatg ttctatttta tggaagtaca tcatttccat aattgaattt cttattaaga 47940 catattattt gcaaatctgc aacaaatgtg catgttattt ttagacgtat gtttggttat 48000 ttctttacga tagagtccta gaatcaccgg ctgaggcaag ggagatgcac atttgaagcc 48060 tctttattca tcttgccaat tgtcctcaag aaacattgtt tcaagtccca ttaatgcaag 48120 caatgaacaa aagtttttat ttttctggat actggatgcc tctggcttat ttttctttct 48180 attctgtttc tttaatagac aaaacaaaag aaaaagtttc tcatatcaat gtgcattttt 48240 ttgcgatttg caaaaagttc aaaaattaac aaaatttatc tattccttga gtaaatgtat 48300 gtggttcaag atgtcaaaga aacaaagtat tgtgcagtgg aaaatgagtg caccttcagc 48360 acctgcctcc cagacatcca tcagtaaccc tctcaggagg cgaccactgt taccatttcc 48420 ttgactagcc ttcctagaat aattatgcat atacaagcaa agaagggtat aagggtacac 48480 acacaaataa gcatactaca tatattgttt ttgcccttgt gtttttcacc taacaatata 48540 ttttggaaat tattccatat taataatcaa ataatgatat tattattttt gatgcctacc 48600 tactattgca ttataaggga attataaggg aagggttgca aatattaaca tctgttaatt 48660 agctttggat atttcttctt ttgcaaatac ttgccagtgt tctttgagca gtcttagaat 48720 tgtggtttta atgttttgtt attgatgatg atttgtaagt ctttgctgtg aaataagatg 48780 accgaccatt ggtattaaat gatgtaaatt ttatttcaca tttcattgtt gtcttttcaa 48840 ttttgttttc tggtggtagg cttattttgt tgttgtttgt tttgttttgg tgtggctatg 48900 gaagtctttt tgggcaatca aatctatcaa tcattttgat ttgatttgtg aatgattttc 48960 ctggattttc ctggatgatc agaggctagt gttgtctctt tgtttactta gattcttttg 49020 acaagggctt tggctattgt gaatagtgct agtatgaaca tggatgtgca aatatctctt 49080 cgagaccctg ctttcaatta ttttgggtat atgtccagaa gtggaattgt tggatcatat 49140 ggtagttcta tttttaaatt tctcggaaac tgccatactc tttctcataa cagctgcacc 49200 atttcacaat cccaccaaca gtgcacaagg attccaattt ctccacaccc tcaccaatgc 49260 tcgctatttt ttgggtgtta tttttgacag tagcccatcc taataggcat gaggatcaat 49320 tgttctgaac ataacatttc tgtcagggtt tttaaaaagt ttccaaaatg acatccctcc 49380 agctccacat attctataag agcaatatca taaattagaa gctgtctatg aaaacttgta 49440 gttggaagat gtttgttttc tgtgggttag ttacatttca catatgcctc atttgtgaaa 49500 taatttctaa tgtgcatgag ctggaattca atgcctgtag tcaaagtagg cttaattttg 49560 aattggagtt gattaaaatg aaatgactaa ttagctttat attgacttgg gagttgtccc 49620 ctaaggaagg cattgggaca atgttgatac tctgattacc tctattccta cctctgttag 49680 cttaaaatat tagtactgca ttcagcaccc agcaagaatt tctagtatct gaaggcagca 49740 ggatacttgc agccattttc aaaccatgga atatggatga ttggtagaga cttctctatc 49800 ttgagtccct tctaatattt catgctttat cttattcata agaaggggct tcactaagta 49860 ggactgtctt gtcttgacca ctaggggatc aaggttaagt ttcttagtct tggtaattgt 49920 cagatttcta gtctttaaaa tagggataat gtcatggagt acctatgtca gagttgcaag 49980 gaccaaacga gctaaggcat gaaaagcatt tagcaaggtc cctggcaagt aagggctaaa 50040 taaacatggt gtttcttgat gttatgtctt gtaaccattg taataatctc agtcaatcag 50100 atttatatca gggtacaggt tcttttctgg ggaatttttc tagcaccagg tattttctgt 50160 ttatcttcta tgtggatggc ttttccttat ttcttctcat tgacaccaag ggattccaag 50220 tcccattctg attgtgtatt gtcaaagtga aaaacagctg tggccagcag agccatgact 50280 ataaccattt tcaaagtcct gtgtgtaaca aacctcaagg attgattttt cactaagcct 50340 ttctccttga ctgtcaaatg acaagcaagg gtatgcagat gataaccccg aacccctttg 50400 atcccatttc caaaatatgg ccatgccata gatgaaggca aattgtttta tttcatcttg 50460 ttggccccat tgtgtatgct ctaagttcat tttggacttc tgtctttact gatagcaatt 50520 tctatttctt tcagacagaa gccccttctt tcataccttt tagttgcatt tcttagcatt 50580 ctggccgcag tcttctacta catggtcctt atttgtcatc tcttcccttt cttcctctct 50640 ccatcccttt tttccattat tcatccagca atatttattg agaaccaacc atgtgagggg 50700 cagcacactg gacattgtct tggcttcctc tgtcactgca gatttaatgg atcactttag 50760 acttatgcct gtattattgc cagggttccc ctatgtatat tgaaacaaat agtctctggg 50820 gatctttcca ttttctgcca ctgatttttt ctttcttttc tttttttttg agatagagtc 50880 ttactagctc tgtcacccag cctggagtgc agtggtgcga cctctgctca ctgcaaccta 50940 tgcttcctgg gttcaagtga ttcttttgcc tcagcctcct gagtagctgg gattacagga 51000 gcgcaccacc atgcctggct aatttttttt tttttttttt ttttgtattt ttagtatata 51060 caggtttttc tcatggtggc caggctggtc tcaaactcct gacctcaagt gatctacctg 51120 cctcggcctc ccaaagtgct gggattacag gcgtgagcca ccacacctgg ccattttctg 51180 tctcttctga ttgggctgtg tatctgagct gtgtcctggg ccactgtgcc atcccacagc 51240 tgacaaaatg gctctcacct ccaggaaact cttacctcag cattttttcc tctgtcttga 51300 gcttttcttt tgttctctgg gaatagtcct cttactttct tggagcttct ttagttattt 51360 tttgatcaat tttttttaca cagttttttg taacggagca aaatattttc agaacttgtt 51420 tctggcatgt gtgtgtctgt ctcatctatc tgcctgtgtc tatgttaacc gttctttgaa 51480 tctgatgccc aatattctat ttgattctgt tgattctgaa aatttctttt tagtcattgg 51540 tttagcattt ctacctcttc tccttaaacc ctaggatttt ctttaaaaag tgttgggact 51600 gatgttctgt tcttcagatt ggcgaacatg gctcaaagac cactagtgtt taagcagcag 51660 cagcttttct atattctgct tgctgtgggc acttgtgatg tcccactgtg gctgccatca 51720 gcagagatgt ggatcctggt ggtggctgtg tctgcctcct ggccagccag cttcctttat 51780 agggaagaaa tgcttccgct tcttactggg gtgtgagagg cgggcccgtc agtcactgct 51840 gctccctagc actcatagca atgtccattt tctatccttt gtgccctgat gataatcttt 51900 ctggtatcat aactgtcttc tcctcccctt ccctgtctcc tcttcctgct ttttttcttc 51960 ttcctccttc tcctcctcac tccagtatca aggcttagct taaatgtgtt gcactataaa 52020 ggcctcatat tttaaaaata taattcattc agtcctcctc tatgcctaag cttatttctt 52080 tgttatggca cttttcattt catagtatag ctctctaccg aggagcgcat acgggataag 52140 ggcagagtat gagtattttt tgagcccaaa aaataatagt catttttatt ggtatagctt 52200 caagcatagt tcatttacat gatttatgtt ttaggaaatt tcaagtgcag aaaaattgcc 52260 cagcagttag agatgattgg gttatcaata tgctccctgt tttttggtgt attttttcca 52320 gctttattga ggtataactt acaaataaca ttgtatatgt ttaagatgta caacttgatt 52380 ttttcaaaat taattatttt tttgaagtaa attttattgt gtatacttaa ggtgtacaac 52440 atgacgtgat gagatatata tagataataa aatgattact acagtgaggc aaactaacgt 52500 atccatcatc tcacgttgtt atccaacact aaaatctacg catggagcaa aaatgcggaa 52560 tacagtacaa tatgattaac tatagttctc atgttgtaga ttaaatctct agacttgttc 52620 atcctatatc tgctacttta tagcctttga tctacatctt ctcattttct tcccttcccc 52680 caaccctccc cataaccact gtgttatgtt ctatttccgt atatttgact taataaaaga 52740 ttccatatat aaatgagatg atgcaatttt tttctgagtc tttgtttatt tcacttagca 52800 caataacctc caccaggctc atccatgttg tggcaaatgg caagatctca ttcgttttta 52860 aggctgaata atattccatt tgtccatttg tccatgaatt gtcacttagg ttgtttccat 52920 atcttggctg ctgtgaatag tgctgcaatg aacacggggg tgcagatatc tttacgaggt 52980 ggtgatttca ttcctttgga tatatattca gaagagggtt ttctggatca cagagtaatt 53040 ctattcttaa ttttttgaga aaatttcata ctgttttccg taatggctgc agcaatctac 53100 actgccacca acagggtaca gggttccctt ttctccacac gctcaccaac acttgctatt 53160 tcttgtcttt ttggtaatag aagggcaggg catcattaat attgtttccc ttacatgtgc 53220 tgaacaaaca cagcagagca gttaccagcg ctaactctgg aactggcttg ctcatgctca 53280 tctcttgtcc ctgccagttc ctaactgcgg aaacttgggc aagttgctta acctctctgt 53340 gccttccttt gttacttgga gctgataaaa ataatgctta gaacagttac tgccatataa 53400 aaagtgctat taagtgtttg ctattatgtg ttgaattcag cttaatagaa tcatcatcag 53460 gatcaccagc aatttattga gtgacagtgt gtgttttatt cattgatcgt cattacactt 53520 agaatagggt cggggatata gcaggcattc aatcaatatt tttgagggaa tgaattaatg 53580 aatgggctag atgttatata tacaaagaaa tatgtctaat ttctttcctt caggtctcac 53640 agatggttga gaatacaaga tggagataag acgaaaattg aatggtgctt aatatgaagc 53700 ccttcaaggc tgcctctttc agaatcattt aggaggctta ttaaaattgc agatttgcta 53760 gccaaactct cctcgatctc agttccatag atctggacgt cggtccaaaa ctctacagtg 53820 ccaagaaagc tccccagggg cttccggtga attcccaaga acagccagga ctgggatcgc 53880 aggccaggca gtaaatgata caggagatga gaggagggag agctctgggg gctgacactg 53940 ttgggaaggc ctggtgggag gggaggtacc tgcaagggca tgtagggctt gggcatgggg 54000 tggacttgat cgtgggggct tagactgcag tagagacatt ctggtcacat ttgcctgccc 54060 atgagctcct tccgtctcct gatgtgcctc agcaatttca tgtgcaaagt acacaagagc 54120 catttgttgg aaagtaccta aatcactcta tttactgagt gctttacttg cacttataaa 54180 tctaaaacaa attttcaagc aaataaacaa gtgtgtggat atggagcaga aataccactc 54240 atggcatcct gaacttggcc ctctgactca gtaattagta tcctaaaact gagttcaagc 54300 atcacatttt attttcaggt tttacatact tcatagaact tggtctctga tgttacagag 54360 atcacagtaa cagtttacct tatctccaga atttctaact tctcaatggt ggcatctctc 54420 attagaacag gtagtcacca aatagttcca cacaaagact ctcccaatgt gtcatttatt 54480 aaaacaaaca aacagatttg atatacaatt aatataccac aaaatcaccc atctaaaatg 54540 tacagtctgg tagtttttaa catattcaga attctgcagc tttcaccacg aattaatcgt 54600 agagtatttt catcacccca gagccacccc tccctacctt tagtcacttc ccatttcccc 54660 ggcccctgat aatcactcat ctgctttctg tctctgtgga gtactattct ggaaatttca 54720 tataaatgga atgatacaac atgtggcctt ttgtgactga cttcttttac ttagcatact 54780 gttttcgagg ttcatctata ttgcagcatg tgtcagcacc tcatttcttt ttgtgctgaa 54840 cactattcta ctatataaat atacttcatt ttctttatcc actcattagc ttgtacacaa 54900 ctggatttcc actttttggc tatgtgcaaa gtttctgtat gcatgcatgt tctcatttct 54960 cttgggtacc cacttaggac tggaattcct gggacatgtg ctaactgtat ttatctaact 55020 ttttgagaaa tcttcaaaat ggttcccaaa gcagctgcac tattttatat gcctaccagc 55080 aatgcatgag ggttcaattt ctccacatcc tcaccgacat ttgttattgt ctttgattat 55140 agccatccca gtgtgtgtga agtagtatct tgttatagtt ttgatttgca tttccctaat 55200 gataaatgac ataaagcatc ttttcaggca tattggccat ttgcatatct tccttgagaa 55260 aatgtatgtt caattttttt ccatttaaaa atttgatgat tttaaatttt attgttgagt 55320 tgtaaggatt cgttatatat tctggatagt agacccttat caaatatatg atttgtaaat 55380 attttctccc attttgtgaa tcttttcact ttcttgatag tgtccttgga tgcacaaaag 55440 tttttagttg tgttgaaaaa cagtttgtat atcttttcct ttggttactt gtgctttatg 55500 tgcatatcta agaaactgtt tctaatcctg ggtcaggaga cttacaactc tgttttcctc 55560 taagagtttt atagtttcag ctcttatatt taggtctgat tcatttagaa ttaatgactt 55620 gtatatggtg tgaggtagag gttcaaatct attcttctgc atgtggctat ccagttgtcc 55680 gagcactaaa tgtttagtcc attttcatcc ttccattttg tcttgtccag gctgttgaag 55740 tagcctcctc acagctctcc ctgctcttag ctcttctcca ccagagtcca tctcccacca 55800 tactaccagt tattcatctt atacacagat atgattatgt cctttcctta ataaaaaaac 55860 tttattcttt ccttagtttc tataaaatag ttcaaatatt caacataaaa ttccaggtcc 55920 tatctagcat gacctcaacc cacctcctaa ttttactgtg ttccttctcc ccacttgcta 55980 ccccatccca gccatccttg acttcttagc tggtctcttt ctggcctgag tgagacattt 56040 ggcctggata tatatgcatg gtatggcttt ggttgcttac tgtggcattg gtgcttatgg 56100 gatagccatt gactttaatt aatggggtgt tatcagcaca tttatcctat tgaaatgact 56160 agaggaaccc ataagaaacc acattttcag gactagtaat ctattttagc atcatttgga 56220 agacaacaaa ctttcatttt atgggtagac taacattcac aaattatgac atatatcata 56280 taatcataat cattaagtta tattttaaat aatcaaccat ccaccatccc aaactctaag 56340 actttgttgg taagttttgt atgtcacagg ttcatatttt tcacattctg acacctacat 56400 tcaaggcctc aaactttacc agagactttt tatcattgag gtaaaactag aagtcattaa 56460 tttaaaaaat tatattattt ttaattatgg taaaaacata aaatatacat tttaccatct 56520 tgatttttta aagcagttta ctagtgttaa gtatattcaa cagatctcca gagcttttca 56580 tcttgtaaaa ctgaaactgt aacccattta ccaacaactc cttccccatt tccttctcct 56640 cccaaggcct ggcaaccacc attattcttt ctgtttctgt gaattttact actttagata 56700 cctcatataa atggagtcat atggtattta gcacaaggtc ctcaaggttc atccatgttg 56760 cagcacatga cagggttttc ttccttttca gggctgaata atactccatt ttgtctctat 56820 atcacatttt tttgtttatc cattgatctg ttggtagaca tttgtgttgc ttccacttct 56880 tggctgttgt aaataatgct gctgtgaaca caggtgtgca aatctctttg aggactctgc 56940 tttcagttct ttgggatata tacacagaag tgtatatagg attaggattg caggatcaga 57000 tgataattat tgttttaatt tttcaactta tcttctcgaa tgagaacact aaattaaatt 57060 tgtggggttt gtgtcatttt agacatagct cacgaagaag atggtaactt taaattgtcc 57120 ctgcaacaat gatgatgggc ttcagtgatt gtcttaaatg agtcatcatt atttttgtgt 57180 tttataacca accctatgca tctgaacaca aaagtcaaac ctttttaata cctcaggtgt 57240 attttacacc aaaatacagg gaaaaggcat caatcaaagc tgcttaacag ctgatatgat 57300 agtgattaca tgtgatatgg tagttgagac tgaaatgcta tttgtaatac aaagattatc 57360 ttaactgagt ctgatttgag gtgaaaaaag gtactaatta gggtgacaat atgaatttga 57420 tttaacttta aagtattatg agagaaaaca tactatgtca caactctttt atataacgaa 57480 ctgggattta ggtatggagt gggtagaata gtggtcaaga gcagggattc tggagtcaag 57540 tgtttggcac caatcctggc tctggccatt gccagctgca tgagtgccac tgggcaagct 57600 tctcacagca ccagattttt catctgtaaa atacggttaa taatggattg tggtggcatt 57660 acatgaatta atatacgcaa catgccggaa tgacatctgg cagggaggaa aagccatata 57720 agattttgta attgattttc tagcacaagc tatccattct taggttgttg tatcttcctt 57780 gtgtcatccc acatatcaat attgtcatct gcaaaaaata tacacgtatg tctcttttaa 57840 ctaatgattt taaaatgtgg actaatcaat gatctaaaat cccccttcct tttagtcaat 57900 tagtagttca taaattgaag atgtgatgga tagaacattt cgtacccaga aagctcttag 57960 attgtgaatg ctgagggaac actgggagat tcagtgagtg cagcacaaat acaatctagg 58020 tgactggaat agtttctaat gaatgaatca ctgaataagc agatgggttg tggaaggcaa 58080 accatgagta aattttttct tttactacag aaatatttct gaaaggtaaa tacccaggtt 58140 tatgatgata gaccttcttt aaactcatgc tatttttctt tctgggtttt gttgtcaaca 58200 caatctcatc tgctctttgc aaccattacc tctcagaatg ggtatgaaga tcaggtgcaa 58260 ccatgtatgt gataatgctt ctaaaaacta ttttttttcc agttttattg aaatatattt 58320 tgcataaaaa tataaaatcc acccatttaa agtacaaagc tcagtggttt tcagtacatt 58380 cacagagttg tgcgatcatt gccacaatta attcctttct gtctccatgg aatctaattt 58440 tgaacatttt atataaatag aacaatacaa tatgcggtct tttgcgtctg gcttatttca 58500 tttagtatag tgttttcaag ggtcatttat attgcagcat gtatcagtac ttcattcttt 58560 ttattgccaa ataagacttc attgtatgga tatgtactac attttatttt ctcattcatg 58620 agttgatgaa catttgggtt tccacttttg gctattacaa ataaaattgc tatgaacgtt 58680 tgtgtgtgag tttttgtgtg gacacacatc tttaattctc ttgagtatat gcctaataga 58740 gaaatttctg agtcatatgg taaccctata tttagcactt ccaggaactg ccaaatggct 58800 gtacgatttt acattccaac cagcaatgtg tgagggctcc aatttcccta cactgtcatg 58860 tacacttgct attatctgtt ttgtcataat gggtatgaag tggtaaaact actgaaaaaa 58920 gtgacatatt catggagtaa aagtaaaatt gaaacatgca gaaagtattc ttcaggccca 58980 gacagccccc cagaattaca gttttttttc tagagtcctt gaaagttgtc tatgcacata 59040 tgacgtatcc ctagatatgt atttgcaaga acacatgtag gagtatacta ttttgtatca 59100 ttctttatca cttaataata tacctaagag caattgctat agaacaggtt gacctgcctc 59160 attcttttta ctcttagcag agtatttttt gtgacgatgt accttcgttc gttttaacag 59220 cttttctaat gaagggcatt ttggttggtt ttgctcttat aagtaatgcc atgcgcatcc 59280 acaagacata caattgttct tgagtacatt tgtgaagata ttcacaggaa aaaacaagtt 59340 atactgctat ataccaccat caacagggga tgagagtgcc tattagccca caatctttcc 59400 agcttaacac tgtgtgttat cagcctttcc catcttggcc aatgtggtag gtaaaaaata 59460 gttcagtaaa agttgatttg acctataagg ggcaaatcaa gtttatgtta taaagcttga 59520 agttcaacat tgaagttgaa ctccagataa tatggttaaa gctttcaaat ttctgagaaa 59580 tatgcaggca tagagattgt atctaaattt gccttaatac atagtatatc catttgctaa 59640 ttgaagaagg tgattggttc atttatttat tcaactggca tttattcagc atttatcgta 59700 tgctaggtga actttaagtg ctagagagaa ggatgaataa gaaacataca ttgcttacaa 59760 gtaatatata gtctaataag ggggacatat atatataaat caataagcat aatggacatg 59820 aaatagaggc aagtattata caataagctg tgtatattag gccataggct aagctactgt 59880 gaaaaaaaag gaccctcaaa tacttgggaa attgcttttg ggaaaagaca aaaaaaaaaa 59940 aaaaagcttg tggaaaaggg tgaaaagtgg acatgagagt aaggagagta agccattttt 60000 aaaataaaat tttattttaa cttcgattgt catatggtaa gtgtacatat tcatgggata 60060 aaaatgaaag gttttgacac atgtgtgcat tgtgtaatga tgaaatcaga gtaattagca 60120 aatccatcat ctcaaacatt tatcatttct ttgtggtaaa gcattcaaaa tcctctcttc 60180 tagttagttt gaaatatacg atgcattatt gttagccaca gtcaccctgc tgtgcaatgg 60240 aacaccagaa ctgattcctc tcacctaact gcaactttgt accagttgat caacctctcc 60300 ccatagccat ttcctcttaa gcaagaaaca tggaaattgt acacattact tctgaaaata 60360 cactggcaag ccacttctag ttgcagggta gacttggaaa atgaagtcta actgggtgac 60420 cctgtgcctc cacattattc tggaggaagg ggatcacgga gctagggtcc ccagtctggg 60480 aggctggtag agaggcagct cgctgtgcta ctctgatatt tttagctccg tgggggaaaa 60540 agaactgcta gacagagctc tgtcaacaca gatctgacaa tctcattcag aaacaagtta 60600 cagagacctc aagtgattaa taaacaagat tattctatag aacatcttat ggtgacataa 60660 tcaatatgat ttcaacactc agctaataaa tgctatgaaa tacaatttat gtaaggtgtt 60720 aattgacatg tcaggtttta aatacaaaag gaatgaggga gggagacatg aatatagatg 60780 ggtgttatca gagaatgaca cttagataca tttcatattg tgtcatgtaa actaatacct 60840 actttttggg atatttcttc atggtttagt ttttaatgta gattcaagag ttttatatat 60900 tcaaactctt catgaaaaaa attcagctct ggttatgtac atccacattt acaggaattg 60960 aatttttctt tttgtacact tgtgagtata ttttttccta tggcaaacgt tttccagaaa 61020 gcaaaagtta tttgtgttac tgtccctgat aatcgatgct gtgtaataaa tcgttctcag 61080 caatggcagt ttggacactg atggacagtt ggtgactggt aatttgtaca gtatgtttag 61140 tgggacggcg ggcaaggggg aaaagtggca tttggttcct cagtcccaga tttgggtcaa 61200 tgttctcata atactggtga gcaaggagcc taattcttta ggaattttaa aaggtttctt 61260 ttagtgaaga acatttccca ggtgtctaat gaaaaattat aaatgaccag gtataatttt 61320 gccaagcttt ccaacatagt tttcctttag ggtgagaaac aatcctttga ttttcttgaa 61380 gtagaagtct cttctcgaat gctaacagta aaacaagacc ttttcagaca gattttgtat 61440 tttgccatca aatgtgcaat ttttgaagat acgggacttg agaatcaggt aaacttcgtt 61500 ctgaaaacca ggcttaattt tatgactgtg attagaaagt tgaaaaaaaa atcacgttct 61560 cacaaatgaa aacaaaagtc agagttcaaa ctgtttatcc tgtttctgta agcttttgtt 61620 tcagaaggcc aaggattatt tgaggagaac ctggaaaatt aactcaaatg gaggaaaaaa 61680 atggcgttta tgcaaaatgc agcaaaagca gacagccttg gagaactgaa gcttaaatag 61740 cgtaagagtc tgagtactag tcttcagata cttaaaacag catttgatag acaagttaga 61800 tatttaagga aacatttaat cagcttggca tcagcattag tggcttcaat ttttggctga 61860 gcctgacttt gccatatgat cctagacaaa tttgcctaaa atgggtgata ttaacttctt 61920 tagggaaagg ctctgtactg ggattttttt gaggcctatg atttatgggg tcaagctata 61980 aaacaggagg aaacacatgc tcatttgtat aatttttaca tatatttggt ccataattgt 62040 acagctaggc aattcattta ttatctgttt gagagtaaaa gtttgattat tttaatgtta 62100 ctacttctgg ttttttctct tctcacatgt tcccagtgac tcctttctga taacccaact 62160 tatcatcata gaacgcatgt aatgctgaga ataagacaca gggtcttgga aaatgaatga 62220 cagcaatggt gctccgatgg cagttttgtc agactttgaa tggtttatga aatcactgtt 62280 gataaaagtg aacaccttct actgaaggga gaaatttagg ggggaaaaat cccaaataga 62340 aggagttaat atccaaacct ggagacttac ctggtaaggt tcacttaact ggtaaaatgt 62400 gatccaattt aaacaaagta tttttagttt tctcagaaca aacatcctac ataaacacaa 62460 aaaatgatat gagacataga tataacttgg ttcacaatat tttccaaaac tataatgtac 62520 cagccagttg gtacagcaca ccaggagaga agatcattat taatgtgcta atagcagcat 62580 tttattttga aacccactct gcatggttac agggctcaaa acaacatatt ctaacaggaa 62640 gatacattac cgaaatattt taatgagaat atttaatatg cattgagagg tccgcatttt 62700 cttgcagaga ccttgtaggt agctctttga gatttctgtc tctatgcatt taagtgaagg 62760 agttggttgg gtattttagt tggcaaattt tgcagacatg tagctttggt agtggagagg 62820 taatagtacc atgccctgcg tgctggcgag gaagccccac agcaacagtg gcttttagca 62880 gctaccagat ttgctaaaag cagccatgtc caattagcag taagtgccat gcacctgcag 62940 ttactaggaa ttgaacctct tttgaggctg aatcttaatg tagcctttta aaaaaatagc 63000 aaaaatctta ctcatactct gagataataa agaaaaatta gcaatggcaa aatggacgca 63060 ctctgaaatg tattcttaat aatgatttag aatatggggt aaatgtagag gcaatgacac 63120 atttaaactg cattattttt aaatactgtt ttatcagttt acttcctaat tttgaattca 63180 attttcatat ctatactgca actgcttttt tttttttttt ttagaaatct ataatattgc 63240 tgcaggctcc ctatgtatgt ttccataatt ttctgcaaag tgttttcacc agaataaaaa 63300 aaaattacag ttcaaaattg caaaactgta gaaaaaatat gctctttgac ttcttttcta 63360 tgtgtcaaat tcaccacaat ggaaaggact acactataga attaaaacgt tattttcaac 63420 agatagtact tattttaaca tgtgttcagc atttaaaaat atttaatatt cttttctaaa 63480 aatgcttaca ttcagaaact atttatgagg gttctgagca gtatgatgtt tctttctctg 63540 atttactgct ttttctcttt tagaggatat tgtaggagaa aaacatttgt taagcaattt 63600 ccagaactac taggttctaa taagaccaat aggctaataa ttcatttcat tgcaactgga 63660 gtgtgtactt ttcctttatt ctcagtcata attttttaaa agagccaaga acaccaaatc 63720 atcaaatcta atgttgaaca tgtagtaact tttatttgct gatcatactc tgagattcac 63780 cataacgaat aaatcataag tattaaaatt tcagcttttt aacataccca ctacactgct 63840 agcctggtaa cacagtcacc aactacacag cttcttcaac tgttgacgtg ctttaaagct 63900 aggattatgg tatcctgcca aaaagatcct acaaactgtc actattttgg tttgtcctgc 63960 cagccattga gaagtagaca atttctatat acacaaacca gtttggaaaa tttatgcaaa 64020 taggaagtta ttctcaaaat gggttatttg attgcatttt tttttttttt ttttgagaca 64080 aggtctgact ctcgcccagg ctggagtgca gtggcgtgat cttggctcac tgcaacctcc 64140 acctccgtgg ttcaagcgat tctcctgcct caatctcctg agtagctggg aatacaggtg 64200 catgccacca ctcctggcta atttttgtat ttttagtaga ggcaaggttt caccgtgttg 64260 actagggtgg tctcaaactc ctggcctcaa gtgatccacc cacgttggcc tcccaaagtg 64320 ctgggattac aggcataagc caccgtgccc agcctgattg tgttttaatg tattggctcc 64380 caaccagtag caacagtttg ggtgcacaga tattgccgta gtgtttctat tcaatgtgtc 64440 aaattattta ggtaaaagtt tggcttaact ttgttgacat ggaatttcta tatcctccag 64500 tttctggttt aactggttta tgtggaaatg aatggaaaca catggttaag ttccccagcc 64560 tccagcttct ctcttcctct tacctatatt tgtacttgcc cacttttcct cttgtgggcc 64620 tgttcctaga atccattatg ttctgtgggt gacatcagcc tgctactgcg ggaagaaata 64680 gaattttatg gtgcccaaga taaaatcgac tatgatgatg cagaatgaag acctggagag 64740 gagtcagaga ttgcagggga taaaaagaga gaaatcagag atgctcccac aaacagagaa 64800 aaccttcaga agcagcagga aggacagagt aaatggagaa caaaaactca agtcaaaata 64860 gtcaatggaa ataaacagtt ttgaattcca gttataattt ggaaaagaag caaacgttta 64920 ttttaaatta agaaaaaagt cgcttataat ttcctgaagt ttagaaaagt gaaaaatagt 64980 taaacctcct gttgttagct aagaagtgtc tattattata agtttgttgc tggagagaac 65040 ataaaaatct ctatctattg ctattttttt tttttttgca taagggatgg ataaaagagt 65100 gtttatttta tttagccttt ggcctgtaaa gtaagattta tgaaacaaag gacaatcgga 65160 aatgataaga attttttcct aatttctaat tatttagcta aaccttgatt gatttctctc 65220 aggctagtgc ccatattaca gcagcagtca gccttcattt atcttacctg ggaccactgc 65280 taaatccgat gtcacttttc agtttttata ttatgtgacc atttagccac atttcaccta 65340 cttgatcatt ccctccatct tgagacctcc ctcgacccgg cttccaacat actttgccct 65400 cctggttttt ctttctctgt tggctcactt tctcagtctc ctctgctggt tgctccattt 65460 ttccacaatc tctcaaaact ggtgctcctc agattaagtc cttggacttc tctccttaga 65520 ttgacatctg gagtcatggc ttcaaacacc acctatcact ccctttctcc ttgaactcta 65580 gacgtgtcca tccaactgct acgtgacatc tccactggga tttctaagaa ctttgccaaa 65640 cttaacatgt ctaaaaccaa attctgggct gggggtggtg gctcacgcct gtaatcccag 65700 cactttagga ggctgaggtg ggcagactac ttgagcccag gagttcgaga ccagtctggc 65760 caatagagaa aagctgtctc tacaaaaaat acaacactta gctggacgtg atggtgcatg 65820 cctgtagtcc cagttactgg ggaggctgag gcgggaggat tgcttgagcc tgagaagttg 65880 attctgcagt aagctatgat tacaccacta cattccagcc tgggtgacag agtgagaccc 65940 tgcctcaaaa aaaaaaaaca aaaaccaaaa ccaaaaccaa aaaaaaaaag caaagagcaa 66000 aacacaaaaa acatattcca aatctcccct ttaaacctcc tcttcttaca atgagtccta 66060 tcttgattta tggcagatcc ttccttccag ttctcaagcc aaacaccatg gggtcattct 66120 tgactcctct cttccatggg ctcatctaaa catcagagta tcctgttggc tatctggaat 66180 ttaaccactt cctatcactg ccattgctac ccacctgctc ttagttatca ccagagttcc 66240 ctggagtgtt ggagccgccg cagagctggt ttccctgctc ctgcctttcc tgcccatgct 66300 ctgtcctgcc agtcagctct gtcctttaaa aatggaaatc aggttacctc atgactcttt 66360 tctttctttt tcttttcttt ttttttttac agaatcttgc tctgtcatcc agcctggaga 66420 gcagtggcat gatctctact cactgcaact tccgcctccc agattcaagt gattctcctg 66480 tctcagcctc ttaagtagct gggattatag gtgccagcca ccatgcccag ctactttttg 66540 tatttttagt agcgaagggg tttcgccatg ttggccaggc tggtcttgaa ctcctgacct 66600 caggtgatct gcccgcttca gcctcccgaa gtgctgggat tacaggtgtg agccaccgcg 66660 cccagccatg actcttttca aaaactcccc atcttctcca cttccattca gtaacagtca 66720 gatctgcatg gccccctcct gaccttctga tgtcatgttc tttgctaccc cttgagtgca 66780 ttgaacatgc ctctgaccca gaacttttct gtttgctatt tcctcaagtg catatcttgt 66840 tccttcattt tcttcaggtg attattaaaa tttcacttcc atgagtcctt ccctggcccc 66900 catatttaac actgcatctt cctccatctt ctttccctcc tccccatgta cattttactc 66960 ccttactaaa ttttttttcc tatctcactt tcttttcttt ttgagacaga gtattactct 67020 gtcacttagg ctggagcgca gtggcgcaat cttggctcac tgcaacctcc acctcctggg 67080 ttcaagcaat tctcctgcct cggcctcccg agtagctggg attagaggcg cgtgccacca 67140 tgcctggcta atttttgtat ttttagtaga gacagggttt catcacgttg gtcgggctgg 67200 tctccaactc ctgaccttgg cttcccaaag tgctggtatt actttctaac ctcctgtgta 67260 tgctacctat ttatttgtct gtctctctac actagaatat aagctctatg agggtagact 67320 tctttgtttt gtccaatgct ctatttccaa tatttataac cgtactggcc ggtaggtact 67380 gtcaattata gtttttgaat aaattgagag taacaaattc taactggtga aaataaatta 67440 aatgggccgg gcgtgatggc tcacgcctgt aatcccagca ctttgggagg ccgaggcggg 67500 cagatcactt gaggtcagga gttcaagacc agcctgggca acatggtgaa accccgtctc 67560 tattaaaaat acaaaaatta gctgggtgtg gtggtgcatg cctgtaatcc cagctactcg 67620 ggaggctgag gcacaagaat cgcttgaacc ctggaggcga aggttgcagt gagccggcat 67680 tgagccactg cactccagcc tgggcgacag agcgagactc tgtctcaaaa taaataaata 67740 aaataaaaat taaaaagaaa ataaatgatc tcacaggata tcatttcttg attggaggag 67800 gagagaaaaa tgtgtatgtg tgagggtaca gagagagttc ctttgcatta gtgagggttc 67860 acatcagaac tgtctaacct ccctactcag tgggtcctgt tacctctctc ctgaatccaa 67920 taatactctg gtgcacacct tttactggta ctgaggctat tttaacgttc cattaaaaaa 67980 aaaaagaaaa catttaaaat acaaaaacaa ggctgtacta ctttaactct gaccttagaa 68040 gactctcagt tttataactg tttagagaaa atgtggaaat gtttgctggc cccaatcttt 68100 ttattactca tctctataaa gaggctttta aggacatatt aaaaagtttc catctctctt 68160 gtctcttgcc tttcttctca tcttcctttc ttgtacccca aatggctgaa agcaagaccc 68220 tgagagtctg gaagaaatat attctggtca gagcagactg agctggagct ggcctagaac 68280 cttggatcct gacctcagaa ttgctgctca aattactgct ctctgaaaga gtgagctcat 68340 gcatgtttat tattactgtg aacaaattta gctgttgttt cacccaaaca ttgaagttct 68400 cgcttggacc cctttgcttg tttgtgcttt tgcaaatgtg ttttctcatg tgctactaga 68460 accaagatga aagcttcagt tctcagaaca ggtgccacga ccgaggagac aaaacaagag 68520 ctatagaggg gtgtggtgtg tgaaactgag aaagcaggta gtttttcaga aaaactgaga 68580 gccaggaatg acttcatcca tttcctgtaa taaggcaatg gtctgacctt gaggaaccta 68640 ttagagtgtg cttctaaaca gaggccattt cgaggctgaa tgtacgggag tatttacctt 68700 tgactgtttt ctgaagcaag gtattttata aactgtaaag tggcttatac aattttagga 68760 atggaaagtt ttgcaaagtc tccaaaatcc ctgggagttt tgaatgtgca ggccatatga 68820 attctttgta gtttcatggt cttgctgttc agcattcttt agagtcacct gcatggtaga 68880 agtttagtag gaatttgggt agttatgggc tggtttcttt gttttcccaa atagaggtag 68940 caaaatggat gctaagaagc aaattacttt tactatttta gatgcctctg gggacatcct 69000 gtcataatgc aacttaaaat atactcgtct cctcagttcc tttttatgta tttatttaat 69060 agtcttcaac caatttgttc ttcattagct gttctacaat acttcaagag aagtcatgat 69120 aatgatgcat ttaggatcag aaaaatatag catgtgtgag ttcctgggga ctttagagaa 69180 tatctagccc agtctttcat tttatagaag aggaaggcca gggatggtgg ctcatgcctg 69240 taatcccagc actttgggag gccaaagtgg gcggatcacc tgaggtcagg agttcgagac 69300 cagcctggcc aacatggtga aaccgcatct ctactaaaac tacaaaaatt aggcaggcct 69360 ggtggtgggt gcctgtaatc ccagctactc aggaggctga ggcaggagaa ttgcttgaac 69420 caggcagagg ttgcagtgag ccaatatcat gccactgcac tccagcctgg gcaacagagt 69480 gagactctgt ctcaaattaa aaaaaaaaaa aaaagaagaa ggagaggaag ctgggggtga 69540 ggacaggcag tgactcaccc agggtctcac actgatttgc tggcagagtt aagcatgaaa 69600 aggtgcctct cctagtctct ttccagtgtt cttgtcatca caatgagtta aaataaaaat 69660 tactagcaac ttgggagtaa taacaataaa cttctcaaaa tctactacat ggtctagaaa 69720 accaaacata aggccggacg cagtggctca cgcctgtaat cccagcactt tgggaggcca 69780 aggcaggcgg atcaggaggt caagagatca agacaatcct ggccaacatg gtgacactct 69840 gtctctacta aaaccacaga aattagctgg gtgtggtggt gcgtgcctgt agtcccagct 69900 actcaagagg ctgaggcagg agaattgctt gaacacggga ggcagaggtt gcagtgagcc 69960 gagatcatgc cactgcactc cagcatggcg actggactct gtctcaaaaa aaaaaaaaaa 70020 aaaaaagaaa accaaacata aaaccagaat attcctgtga gttccattac ataggacaat 70080 atggtcctgc tgatctatta aaattatgtt tataaattag aggctcttca ttgggagata 70140 tacttaatgc tagatgacga gttagtgggt gcagcgcacc agcatggcac atgtatacat 70200 atgtaactaa cctgcacatt gtgcacatgt accctaaaac ttaaagtata ataataataa 70260 taataaaaaa agaataacag gaaaaataat tagaggctct ttactgtatt taaggtgttc 70320 aaataattga agctagttta gtatctcctt agccttcccc agcatgccct gcagctttga 70380 cgctgcagaa caccagttgg tggctgatat ttagatgatg gaaatcttgg acacattttc 70440 atttttgata aaatgacatg gcactatggt tacattttac aaatattttt gcggatgtat 70500 atcaggtggc atacccaaga aggaacagac cttcctcagg ggtccttctt aggaaagtac 70560 agctttgctt ctctgatcat cagaattgga tccttcaggt attaggttgg tgcaaaagta 70620 actgcggttt ttgccattca aagtaatggc acctgaaagg gttggtaaaa ttcagaatat 70680 tataaaatca gtaaaagctt aatcaaattt gcctaaatct atcctacaga ttagtctatg 70740 catggtttat taaacaacct aactgaaaca cacatgcata tgtgtgagta agctgacatc 70800 agggatcacc ttatcatgga aaatctaggg aaggttggct caatcttcaa tttgtgaaga 70860 ccaattcccc taccacgtcc atatatacat attcccagga gacttgtttc ttcagggctc 70920 tctttggttc tcagctcttc ctttctgaat tagtgggtca ctttaacctc ccttgggtca 70980 cagtcgtgtt ccacactggg tgggtccaga ggtagaactc attgcctttc tttgaatccc 71040 acacaagacc acccaacaag gcattgtagt tggtggaaaa ctccattgaa gaaagggtct 71100 atattgcaac aaacaagcat ctagaaatag aatattaaat atccctcctc ttaaaaatcc 71160 attgtccaat tcagacttca gcataatgta atcttctgtc ttcttttctc tgtgtttcca 71220 tcttgagagc catcctatta tctgtgtcct ttctttgttg tcttaggaag aatattttgg 71280 cttatccttt gttttgttct ctccttcccg gacctattat ggtaaatgtg gaatttgcag 71340 ataggcttat ttgcgctccc cagcctgctc ccttaatgct ctctggtaag acacttcttt 71400 gagtcctccg aggcgagttg ctgcccccca gcacctgctc ttccccatcg caacccatga 71460 cagtaaacgc actgcacata cttatcccac agactgctgt gagaactaga tggaggctat 71520 gtgtgaagct gcaagctctt ggtaaagtgc tacagaaatt ggtagacact gttactatga 71580 taagatgttc agaaaataat ggatcgatta aagtttcact tatctattaa aagataaaaa 71640 actctatgat tgagaccttt ttggaatatt ggaaaatatt tttgtgtgct tattagcata 71700 ctgatatgtt tcagtacaca tttcatggat ttatggctaa ggatgttact ttcaagaagg 71760 taactataca tcgctctcta ctagcatgct gttctgttcc tgagaaatag tggctgggcg 71820 aagggtatgc aaacatttct taatatctca tccaatacca ttttcccact actaattatt 71880 caacacatgg aaatgtaggt caaagcatta aaaaaaaaaa ctagaacagc aataccttgg 71940 tggttggcag gtgtttattt aaaatattta cgttttagcc ttatttttta atacttcttt 72000 ttcatatata ttagatattt aactaaagaa aataataatc attctcatgg aatactttaa 72060 aatagtagaa acaatcatga atagaaatga agatttaggc ctatactacc ctaggctctg 72120 tcattcttat tcctaaccat ttgcatagga aatttagatt cacccacttc tctttcttag 72180 aataagattc acaggttttt gggcatattc ccattgcatg cctgactggg gaggtgttca 72240 aatccctgct tttctactcc tcagccctgt gaccctgagc aatttctgtg gcttggtttc 72300 ctcatctgta aaataggata ttaatagaac atatcccttt aacgttgcag tgatcacatt 72360 aattagttga tgcaaaacag tccatctaga acagtaagcc ctcaataaat gctagctatc 72420 attatcattt catagccagc cccaccatgg atgggtcatg tgacctgaag caaatttaaa 72480 ttctctggat ttcagttatc tctcattgaa ggaattaggc tccatcagtg gttctcaaac 72540 tcaagtgagt atcagaatca cagggagggt gtgttatgac actgaaggcc gggccccacc 72600 ctcagaattt cttattcagt agatccagga gggagtgcaa taatttgtat ttctaaaaag 72660 ctcccaagtg aagttgatgg ctgatctgga gacacacctt gaaattcttc tgcttactct 72720 aaacaaaacg tgctttttta tcttgagtgc acatcagaac cctctgggga ggttaaaagt 72780 cccagtgaaa tcacaacctc tgcagatggt aaccagatct tagtggcttt taaagttctc 72840 caggtgcttc cattgagcag ctaaggttga caacacttct aacaccgctt tcaggtgaaa 72900 aagaactatc attctaactt aaatgaagga gaaaatgaat tcatcattct gacaccgtta 72960 tctattcttt catgcatggg cttatcctat gagaaataaa catttactaa ggtgtatgca 73020 tgtttttaga acatccattg ggaagcatgt tgtacagctt gtagtaaaac agcatggtgc 73080 atgctgaaac tgttataggc tttgcaagtt attttttata aattagtttt gctggtgtgc 73140 tgtttgatta ttggagagtg gtgtgaacat gtttctatgc atcccagggg gttgctgtca 73200 cctttaaggg gcctctttaa atcccagctc tttcatttac aaattctatg accttggatg 73260 agtttcttca cttttctgtg ccacaagttc tcagtaaaat ggagataatt atagaactta 73320 cttcatagag ctttgagaat catacaggta aagttatttt acgtaattag cactcaaaag 73380 tgaccattaa taatctaacg ttttaaaata tattaatagg ccagatgcag tggctcacac 73440 ctgtaatttc agcactttgg gaggctgaag tgggtggatc acttgaggtc aggggttcaa 73500 agccagcctg gccaacatgg cgaaactccg tccctactaa aactgtaaaa attagctggg 73560 catagtggcg tgtgtctgta gtcccagcta ttcaggaggc tgaggcagga aaatcgcagt 73620 gagccgagat cacgccactg cactctagcc tgggtgacag agtgggactc catctcaaaa 73680 acaaacaaac aaacaaaaat taatagttta aatattttta atatatttca atatataaag 73740 atgtaatttt tattttaaat atattaaaat agataagttt aaaatacata aagtaaatat 73800 ataaaattaa tatgttaaaa tgtttactga aagtttacat ttttctctgt attgctaaga 73860 gcaatttatt gccttatatg ttgtgtaata tctagaaaac acacctatgt aatttccaaa 73920 ttataaccac cttggctcct ggacaagtag gactgtgtct gatttttttt tttgcatcct 73980 tgtcactacc tgccactctg agatcacttg ttgtctttcc atatataatc acctctaggt 74040 acacttcttt cattatttct acgcatcctc tccactttgc tgcattcttg tgtgcattct 74100 tttctcccac gttggaaaga aatatgcata ttgagcgatt ccaaccccca aaggcaaaaa 74160 ttactagcca gtgttgaaaa tgaaagcaag gaattttttg gttattgttg ctgtaacttt 74220 ttgatgtgcg tacatatgtg cgtctttttt ttccccctag gggtggaatg gggtggtgtt 74280 agtcagggat tactgacagg acggtgttgc ctactgtgtt ggagagacta agactgggga 74340 aagattctcc aaggctggga aatgcagacg tccagtcttg gaaaacagtt tgtcgttggt 74400 cgttatgtca gaagaggagt gtattcctgg aagaaggccc acaaaatata cccagagccc 74460 aggtgccttt ctaagacgaa tcaacattca ctcacaagtt cagctaatat atgacagaaa 74520 tacaagaatg aacaagactc ctgacttaag cttacagctg atgggaaact tgggaactgg 74580 acagagaatt aaaatacaac gtggttaggt acaacttacc tgcgccagag gagtgacgga 74640 aggccttgga cggggagtga tgcctggagg atgacagggc gacaggtaag ttagggggct 74700 gggaagggga agggcggccc tgtgggtaaa gggaaggagg ttaaagtcag cagggaaaca 74760 ggcagttccc tgttgctgga gcaaagcgcg ggggtgtggc tctcctgtct ctggctttgc 74820 tgtcaacagg cgagattggc aagtagggcg accaaccggc ctggtttgct cgggaccggg 74880 gtttcctgga aggtgggact ttcaatgcta aaactgggac agtcctgggc aaacaaatca 74940 gtacggttgg ccaccctatc tttgtgtggg catctgctaa ctgagtcatg ggcctgtctg 75000 gtttatttat ttattttttt tctgcctgag taacagaaga atgtgttaaa catatggagt 75060 atggaagaag aaggagaggg gagataggat ttttatgtta tagattggaa gaagacatcc 75120 ttgatgaagg agatgttttt actttggaga aggactgcct cagccgcgaa agaccaaggg 75180 gtggcaccac agggagaagt ctgcactgcg cttgtcagga cggccagtgg ggggctgctg 75240 agcgcaggga gtcagtcctc gcaatgaaga tatagtctcg gggagataat gctggaaatc 75300 gatggaagaa gtggaacagg acacaaattt agtggaattt ctttacaatg tgtgcttctt 75360 gtcaccagtt cgttaaccat gataaaaacg gttatgttgt tacattcatc aagatccaaa 75420 ttttctacca ttttaagatg tctatcagtc acaatgatga tcactgaaga ccgaacgaga 75480 tcatttcctc taaaaattat gttacattta tccataatgg catcagtgtc tgttacacgt 75540 ttgctttaat tttgaggtca aatacgacat ttgtaaatct agcacttcat gtgattctgt 75600 aagcactaaa cagctaaaca tatttacttc ttttttttga atcaattaga acagtgctgt 75660 acaatagaaa aatagaacag tgctgtacaa tggaaacagt gctgtacaac agaaatctgt 75720 cagccacacg tgtcgtttaa acttttctag taatcacatt aaaattgtaa aaagaagcca 75780 ataaaagtaa ttttaataat atattttgtt tgacataata tagctaaata tcaattttga 75840 catgttctaa atataacaat tattaatgaa aaatattaca ttcttttggc tttgtactaa 75900 acatttgaaa tgtggtgtac gtttttcact tatagcacac gcaattcaga tgctacattt 75960 ttattaggaa tatttaatct gtagatagat atcgtaaaat ttacatttga aaaaaataga 76020 ttcagacacc taagttgtta caagcatact taaaagtttt caatgactga attgagtatc 76080 agttttaaaa tttaaatcaa tgaaattaat taaaatgaaa tgaaaattta gaaactattc 76140 ctcagtcacg ctggctacat ttcaagtgct tcatagccac atgaaagctg tattggacag 76200 caaagaagta gaatatattt ggaataaaaa ttttaaagtg gacacattgt gttactctcg 76260 ttagccatgc tattgctatt ttttttccta tagctaatta aaaccttaag atccagtagg 76320 ttctccacct ttttttaaag cattagttcc atgtcgaccc tgtagatggc agcactttct 76380 tcctaaaact acatggagga gttgcctggg cttgtcactc agattctggc acttttcata 76440 gaaagagtct gaattatctg gaaaattctt tggtaacata ggtcagaatc ttttcagctc 76500 tattgttatt ctgcacagat ggctgttgct tatgaaaaca atctctcagc ctctagtcca 76560 ggatattact cattcctcag ttcaagaaac tctagggtga gaggagaaag gggttcaatt 76620 acagaactgt tatcaaaatg cgttggttta tgcacatccg tgttttggac atggtgattc 76680 caagagactc ttaataaaac ttttcaaagt agatgagaga cagtttttcc ctcacatgct 76740 gtggcaatat taatctatgt tttcatgttc cactggactt tgtaattgaa ttttaaggaa 76800 tgcatacagg gcttcatatt tatatataaa atatccatat ccagtgttga aagaaattaa 76860 caataaaata tgtacctgta taaaatttgt gatttttgaa gcacccctct cttcctcttc 76920 gcattgcatt tgtggtagga gaacatgaga caaggaacga ggtactaagg acaaagaagg 76980 agcgattcag aggtggattt cctgaagacc aacaacattt ttgcatagct cgtgaggact 77040 ctctgatact aaactccaat aaatgatggt ttggtgtttt gattgctttt gattgacatt 77100 taaaaattac aggagactga gataggagga ttgcttgagc ctgggaagcg gaggttgcag 77160 tgagccaaga ttgcaccact gcactccaac ctgggtgatc gagtgagacc ccatttcaaa 77220 acaaacaaaa aaataaaaaa taaaaaaaaa caaataaaaa tcacacgcct ctttttttca 77280 ctcaatctgt tttccaaata aaatatcaag attctatttg aattttaata atgattttgc 77340 tgagttttat agcttgaata ctatggcaag tataatgtct aaaatgctgt gattttgact 77400 taagaaaaaa tttacagttt tcttaatata ctctttagtt cttttaaact ctaatacatg 77460 aaatggattg ctaatgaggg taggaagggg gaaagactgg ggagaaaaat agctaacttt 77520 tctagcgata gatacatgtc agaagctgta gtaggttctt ttgcatgtgt ttacttacat 77580 taccttctgt aatctgcatt gcaatttttt catagacaag gaaacctaga cttagagaag 77640 tacaatacct gtcatctcgt aaatgacaga tatagttgag caaatctact gaaatggttt 77700 agcttcttat ctttccagac aacagataag gacttattct atatgaagac atctgagaaa 77760 tgaaaatatg gtttcaggtt catagaatct tttacaccac gtatttctgg ttctctttct 77820 tctattcaga tcattctttc atctgtttct tttgtcttct tttccaaaat gtagcaattg 77880 ccccaaattc agtacttgtc tctcttctta acaatcacat ccaatcccat ggcctcaacc 77940 atcttccctt gcatataatt tccacattta caactttatt ctcttgatta ctcaggataa 78000 gataattgct gaacaaataa cagcatatat ctcagcttaa gagagtaaaa gtttattttt 78060 ctctcatgca aattctattg cagatattcc ccacctcctt ccctaggttg tcctcaaaat 78120 gcagtgactc agggaactcc tctttctgtc ttaacctatt ttaggtctta gacccctttg 78180 gcagtctggt gaagccaata aatctcctct caggacagtt tctaaatgtg ataaaagaaa 78240 aaaaagatat agtgacagat ctaataatta aaattcaaag ttaatttcaa attagtgata 78300 ggtaaatata tttcaagatg tctgcactga atacagcgtg ataggtaata tatatgattt 78360 atcttggtga caaagacatt ggtattgcta acactattat agctgccatc tgtattcaca 78420 aagggagatg tcaaattcca gttaaaagaa agattttctt aacccaagtt cataggactt 78480 cctgaatggt acagatgcta aggtctagtg gctccacaac taccaaagcc ttcttagtgt 78540 tctctgctgg atcttatgca tccaattgac tgacaagcaa agaacctgca gaataatagg 78600 agacatttgt tgggtgggga gagcaaacct agaaggggca tatacccctt acaattatag 78660 ctctatgcgc tagaattagt tatatcattc ctcctagata tgaggggact aggcactgta 78720 cttcagctgt gtgtccagga aaaaggtaag gtatggggaa tgtggagcaa taattatttg 78780 aagcaagaat caccagtgga tgctaaaatt cgtgagggaa aacaggacca gaaacaggat 78840 atttttaaag tctccaagta cctccacata ggatacttat taattgcaaa gggaaaatag 78900 taactttaca gagaagaaga aatctggcag acactaccat atccaagtga tcaaaggtga 78960 catcagtagt gggacacatt aacatcatgt gcttctgata tgatacacaa aggagaaaca 79020 acctcattct tgtgatgttc ctgccaaaaa tccataacct gaaagaagca tcacaaaatc 79080 cccaattgag gggcattcca caaaatagct ggctagaact cttcaaaatt gtcaaggtca 79140 tgaacagttc cagaccaaag gaggctaaaa gagacaggat gcctcaatgc aagtataatc 79200 ctgaattggg tcttgggtca gaaaatgggc attagtaaga caattggcaa aatttgaata 79260 aggtcaatag atttgaaaat aatactgtac ctatgtgaat ttcctgactt tgatcaaagc 79320 actggggtta agttaaaaca taagatgttg tttttggaaa tacatgctgc tatatgcaac 79380 ttactctcaa acatctcaga aaaaaaaata gataagttca tagatagata gatgacagga 79440 taataaagca agtgtgataa aatgttagca tttggggaat gtaggtaaaa gtatatggga 79500 atattttgta ccattttctc aacctttcct ttaactcgta aattacttaa aagaaaagca 79560 ataaccctgg ctcttataaa actaaggaaa atggtccatc ctttcctgtg ccttgtgttt 79620 tcctgctggt caaagaacct ttggtaatga caatctgagt tggtcactga tattctagta 79680 aattcagaat ataacttcct gggctatgta gaaaaatata gctcttcata ttttaattca 79740 ttttcctgac agcacgtttc tgtgctttta tgtatggata ctgcctagta atgtgcacac 79800 cagtcctgca gatcctggaa cattttatta tcttgatatt gacttacgta tttaggtaga 79860 tctgaatagc agaattgtca gtcgtttcac caagacatta tcgggaaatc tggacttgga 79920 agtctacttc tgccaggcat ctctccacgc tggcttctgg gccacagaag aaaagatcta 79980 atcaaactca tttattaaca aaggcttata atattgaata gcagcttcca ggaatctaag 80040 aaaatgttca cttttatttc tgactaagga ggaactatta tagtcttttt ataccagtta 80100 gaagtgatga cttggtatta aacttattct aattctcaat agccctgatc tcgactctga 80160 ccacatgcgc gcacaccctc ccccaaccct gtaagtgtga ttatggcaag gggaaagtta 80220 aagtggagtg aatggtgagt cgtggaatga cagagagcat ttagcatttg taattgacag 80280 agttggtgat tgactgaatg gacactgaat atctaggcta aaagtaattg aatgtggatg 80340 gtgtagtgag atggagaaca ctagcaggaa gatagactgg gctacgcagg ggctagatca 80400 tgtgttcagt ctgggatata ctaagtttga ggtttctgta aaatgtccat gtgaagatgt 80460 ccaattggga gttggatatt tatttatgtt tccattccca tcaatcgata agcttcagag 80520 gaaataagag tgtaagattt ttttgaacaa caggaaagga agattgtagt aagatatgat 80580 ggcataatgg tatatggaag agttttaaat aaaagttagc caggcatggt ggcacgcgtc 80640 tgcagtcccg gctactcggg aaactgaggc aggagaatcg cttgaatccg ggaggtgaag 80700 gttgcagtga gccaagatcg caccactgca ttccggcctg ggcgacagag tgagactcca 80760 tctcaaaaaa aaaaaaaaag ggatgaagag ggatgaggag aactcaagtt atattagcct 80820 gaatggaata gatgagtgga gagatgggca tgataggtga gttaagaagg aaattctttg 80880 cctcagcaac caactcagat gctttgtgaa tctaaattat gtgttgacat tctagtagac 80940 ctagacctgg gataattcac ttcagcatta tgtaatctta atttttcatt tataaataag 81000 aaaatattat gcaatacttg ccatagtttt ctaaaagctg aactcagaat gttaatgaaa 81060 ttaaaatggg aaagctattt tgcttagaag atattttgtt ataaacattt cttaaatgaa 81120 gaggctctag aaatatttat tttatagaat ttaaaatata gccatcacta ataaaggcag 81180 gcataattcc aacgatttca taacacatca gttattaaat ctaattaata tataaatgta 81240 actaatatgt aatttaatat aaccctaatt caatgtttaa ccaactgaag ctggttaaac 81300 tatgaagaag aatcttcaaa ttgaccattt ctttccaagc ggtaaaggtg atacgggatt 81360 ttgtctatac atatagagca aaggagaatt aagccaagat ttagaatttt aggcaaaaag 81420 tgtttatagt atcattaagt ggttacatat gtaattttac tgttataaat atgactgagt 81480 caattttttt ttcaaagatt ttgtcacaat gggaggcaca aggagtttag acagatgaag 81540 actctttcta gaaatctacc taatctatca cattagacct ggagataatt ggtttgacaa 81600 tttcagttgt ttctcagcaa aaaaaataag aaactaaaag tgttcagatg gcagagaaaa 81660 aagtttgaag aggagagaaa gaagaacaaa aagaaaaagg aaacagtaga catataaaga 81720 aagcacctaa accagtgaga tgccccagct atgcaccagc agcatggtgg attacagtag 81780 agtttttcta cagaactatt gtaaatcact ggaaaatagt gtccaactta tttgcttaaa 81840 attttcagtt aatgtgctcc agcagcattc tgtagacaac gactctcact ctccccttat 81900 tatggaggca gagctgtttc tctttgtccc gttctctagc ctgtgatata ctttttattg 81960 ctcaagagct atagaattgt atccatgcct attgttgtcc tcctgatggg aattcatgta 82020 attgaaagcg tttatcctct cttagtagaa aaattgggca cttggaggca atgaaaatcc 82080 cccacctttg tccacggcac tggaaatact cttcagtctg ctttgttcta aagtttctac 82140 ttttcccagt ataacctgtt gaaaatttag tccttcatga gaaatacggc tggaatttct 82200 tgtggcaggc tggccgccgg tgttcatgta gttacacctt ttgttgctat ttcaccactg 82260 atcaaaaaat aaaattgtat tttttcaaaa gaaacatgga atgacatgaa gaaagtcctt 82320 aatatatcat ggagtgaaaa acagcaagtt gccatgcaaa tgtcaaatag atcctatatt 82380 tttaaataag caactgcata tgtatcattt aaatatatat gtttagatat ttgctaaatt 82440 atgaaccgca gttacccctg gggagtgagg ttaggaaaag taaagtgaga ttttcacttt 82500 ttacattata ctttttactt tacccacttc tgtattgttt gaatctttaa aatgaacaag 82560 tgttattttg taattaaaaa aaacaacaac tgacaaataa ctatggggag taagaaatta 82620 cttggaatgg aatatgttta aataattaat ttgttgatac actgcttgac tattattttc 82680 ttttgctaaa tcaaaactcc cctgcttttc tcaggaggtt gttttgaaaa gaagggtaaa 82740 tgtttctaat gaaatgaaca gctcaacctt cccacctcct gcctaaatgc ctcattttgg 82800 ttttgttact aacaaatgca acacgcaagg ctttatggta aagcaagcaa tgtgggtttc 82860 taacagggca gtacacaccc gtagttgctg ggaaaccact ttagtaatgg tggatttatt 82920 gaattggaac aggaatggag atttggaaca acaggaagtg aggtacctgt aggggtctca 82980 gttgtcctgg gcactgtgac atggcaccca aatgtcatgc aagagtggcc cttccaacat 83040 atgcaccaat ctgaatctct ccaaagtttc ttgattacac cataaaacaa tgaagagaac 83100 agcattgcca ataacttcag taataacttt tgcatcatat tacaaagggt ggtgggtggc 83160 actttgtgtg gtcatgggta tgtccaaaag aagggagtgg tggctagact cagttctcct 83220 ttagatttta aggcaaaatt tagcaaactc tatggcagat tcttcaacta tttgtcagac 83280 agacattgtc tacttttctg gggatttatg attgaggccc cttttgaggg gagctttgag 83340 tgcagtgagg ccagatagaa gggccaagaa ggatgggagc agctgcatgc tagtgagcaa 83400 ttcaaagttg gattgtgctg actggaaaat cccggttagc aaatcaacta tcacagactt 83460 catattcttt tcagatgtgc agcctttata acatatttgt aaatgctaaa ggactgctcc 83520 acagggaggt tacaaagaga aaagctctgg gtggttgtaa aatggacaaa ttgtaaagcc 83580 ttactagtag tcttaccatt cctctcagct cataaaaaag tcctcctctt catttgacta 83640 tgcctcaaat ctactgcttc ttggattatt aaacactctt ttcctccagg atcttaaaat 83700 ctctctgtta taagttgaat tgtgtccccc tcaaaaatga tatgttgagg tcttaaaccc 83760 cagtatccta gaatgtggcc ttatttggag gtggggtctt tacagggtta atggaattaa 83820 aacaaggcca ctagggttgg ccagtccttt ttataaggaa tccagtatga ctggtgtcct 83880 tattaaaagg gaaaatttgg acagagacac acacataggg agaaagacgt gatgatgaag 83940 gcagagtggg gggtgatgct tctataagcc aacgaacccc aaagattgcc agcaaacccc 84000 cagaagctac agagaagcat gcaacagatt ttctatcaca gccctcaaac agaaccaacc 84060 ctgccaatgc tttgattttg gacttttagc ccctggaact gtgagacaat acatttttga 84120 tgtttaagcc acccactttg cggtgctttg ttccagcaac cttgggaaat gattacactt 84180 tctcatctgt gatcacagtg aggccttgtc acaatcttca ctcattcctt ctatagaaag 84240 ctgaaagcct atggacaagg ataattgcct tggctgacgc atatgtttga aggcagctgc 84300 tggcaggcaa ccggagactt taccctggtc ctagtggaga ggaagtctat aggaggaggc 84360 agggagcctt cctggctggc aacccagtga ctcaggttgt tttcttactc caaggatctc 84420 tgtgcaagta ggaatcctga catcttctct ttttcacttg tttatgagac cctgcttgtt 84480 gtagagtaaa gagcagaact taagaatgga atctaatcac cttgaaagaa taatctctca 84540 tctcctctgg tggcaaagga ttgggatgtg gaggttatag ttggaaaatt gattcctagg 84600 tcaatgtctg tgggtgaatt tctctttgaa ttgttatcag caatgttatg gtgttcggtg 84660 gctttcaacg aaataaacac acctgacatc cttagtaaag agaaagcttt ctgaaataag 84720 agtgagggac agactgggac atgatgcttt gcatgaaata ggtgttcagt aagtatttgt 84780 agagttggaa gaagttagat taaacagggc tattgtatgg cacattgtca ttagggagtt 84840 agagagggct tctggaaagg tttggtcagt tttgacttac cttgcaataa atttggacta 84900 taataaccat ttcactagtt tgtaaaaggt actggcaacc aaagatgggg aatgccactc 84960 aatctcactt gttctacttt caaaagcttg ctttggtcac attgaaaggt tccatttggt 85020 gaagtatagc atatcacaga aaacaatgga gtttgggagt tcgggaacaa atggttgttt 85080 tgtgataatg aataactttg acatttcgtt tgaagttaag ttatgttgtt tgaacttttc 85140 tgtccctgaa caaggcatcg tatgccaaga acaggtaaca gtttctggat cactggggac 85200 tcattagtca tggatggtta gtggtactac attgtggtct tccttcaata ttgaaagctg 85260 taagaagctt gtgacaaatt cttaccttgg ccctcacaca gtactggtag ggctgggatg 85320 ttattgcttt tgtccaccaa cttccaactg tagaagtcta ggatgatcac agcagttaga 85380 gatgatccat ttagatagtc tatattaagg gaaagtatcc ttcatccatg gtgttgaaca 85440 ttcgtaggat taaaatgaaa gaagccaaaa cctttctaga tctttattgg tatatcaaca 85500 gaattagctg attaggtatg cagaaaaaac ttgggacttg aagacaccat taaataaata 85560 actgtacata accatacatt aaataactgt aacaccatta tataaataac taactataaa 85620 taaagagctc tacattcaaa ctgcttttca ctgcatttgt cagatttcac ttttaatata 85680 attttagttg acttatccct catcttacct taagaagata atgagttgag gtggatcttg 85740 agccagtgtt tagtccaata tagccctttg acttggggaa agatcaaact tcgaaattta 85800 tatgcatgac tcctctctgg gcaaggactg aagtggcagg agaggtgaaa gaaggaatca 85860 ggacaaaaag tagatgctaa aaggaaaaca gtctgtcccg tggagaggaa gtacccaaag 85920 aaacagaaga actccatgat ggagagtaat acaagttgaa tatcccttat ccaaaatgct 85980 tgcgaccaga ttgttttggc tttgggatta tttcagattt tggaatattt tcatacccgc 86040 tcagtatccc taatctgaaa atccaaaatc tgaaatgctt cagtgagcat ttcctttcag 86100 tgtcatcttg gccctcaaaa agttttggat tttggagcat tttgaatttt ggatttttgg 86160 attagggata ctcaacctgt actagcgtgt taaaacagtc ctggccaggc gcggtggctg 86220 acacctgtaa tcccagcact ttgggaagcc gaagcgggcg gatcacaaga tcagaagatc 86280 gagaccatcc tggctaacac ggtgaaaccc tgtctctact aaaaatacaa aaaaattagc 86340 tgtgccgtgg cgggcgcctg tagtcccagc tactcgggag gctgaggcag gagaatggcg 86400 tgaacccggg aggcggagct tgcagtgagc cgagatcgcg ccactgcact ccagcctggg 86460 tgacaaatcg agactccgtc tcaaaaaaaa aaaaaaaaat ccaaaaaacc caaaacagtc 86520 ctagaggcta cagcctagag cagtgggcaa agagaagcag aatctacaga agatattgtt 86580 caaggcctgc tatgctaggt ctcagatagc accagaactg ggcagggcaa gaaacgtcag 86640 gcccaggggt ctggtttaac cagaagaggt gctgaatttt aggatctgaa tagcaagggt 86700 tgtggtcagg aagtcagttt catgtaagaa tgaaggtgag cggatcttaa atccctgaaa 86760 ggaggcagag agaagaatat aggaaatggg tggataattt ttgttgcgag taaaaatgtt 86820 caggactttg gaggcaggaa gagcaggtaa agcaagttcg aggaaagagg ctgggtcaga 86880 ggggatctga aagcaggagt cagaaacatc cattggaggc ctggagaaca taaatgggag 86940 gtgaatagac tggggacata gtgcctgggt ggaaagaagc tggctcgagt ccgaaaccac 87000 aggctgaaat attaggaaaa agagacccag gaattcagtt cagaatagga gggatttgtg 87060 gggcaagacc agtggttctt ccagacattt tatcagagat aacaaagcag aggctgtctg 87120 ttctctgccc ttggtgtgag aagaaaagga ctgacaggag tgcttggcag ctcaagccag 87180 ttatggagct gtgggtgcta gtggctatta actaccaggg aattagctct gctgaatgag 87240 tcctcacgca gaggcaggga tagaacgttg cattcagaag actggccacg gaggccggct 87300 ggggtggctc acgcctgtaa tcccagcact ttgggagacc aaggcaggag gatcatctga 87360 ggtcaggagt tcgagatcag cctggtcaac atggtgaaac catgcctcta ctaaaaatac 87420 aaaaattagc caggcttggt ggcgggtgcc tgtaatccca actactttag aggatgagag 87480 aggagaatcg cttgaacccg ggaggcagag gttgcagaga gccgagatca cgccactgca 87540 ctccagcctg ggcaacaaag agtgaaactc cgtcttaaaa aaaaaaaaaa ggaaaagaaa 87600 agaaaagaag agtggccaca gattggcttg gctggagaag gcattttttt atagggagat 87660 atacgtgagt ttgacgggat gggctagcag gcggacattc aggttttatg ggataggcaa 87720 aaaggtacaa atggtatttg gggggatgtg aatggcatct gagaaaggtt gatccaggct 87780 tgtgtggaag ctggctctga gcataaaatg ccagagaaag gcttgtacaa ctctgaggtc 87840 ttttcttttc ttttcttttc tttttttttt tgagacagag tcttgctctt gtcgcccagc 87900 ctagagtgta gtagtgtgat ctcggctcac tgcaacctct gcctccctgg ttcaagcgat 87960 tctcctgcct caccctcctg attacctggg attacaggca cctgccacca agcctggcta 88020 attttttgta tttttagtag agacacggtt ttaccatgtt gcccagggtg gtcttgaatt 88080 cctgacctca agtgatctgc ccacctcagc ctcccaaagt gctgagatta caggtgtgag 88140 ccaccgcacc tggcctattt tctatttttt aaccagtccc aagtaagggt attggttagg 88200 gttgaggcaa tggaaatctg aaagaaaggg tgagttaggt atttcactgg acacatgtgg 88260 agaatgttgg tgatttaatg cagagggaat tgtggttaaa aaggttaatg taagaagggt 88320 catgtgggga ctggaaatca caatagagaa acagaggcca gaatgctgaa ctcataggaa 88380 gtgggtgacc atgggtgatt aaaatgtaca atagggctgg gtatagtggc tcatgcctgt 88440 aatcctagca ctttggggga ctgaggcagt tggatcacct gaggtcagga gttcgagacc 88500 agcgtggcca acatggggaa atcccaaccc tactaaaaat acaaaaatta gccgggcacg 88560 gtggtgcatg cctgtaaccc cagctacgtg ggaggctgag gcaggagaat cgcttgaacc 88620 caggaggcag agggtgcagt gagccgagac tgcgccactg cacttcagcc tggggaacaa 88680 gagcgaaact ctgtctcaaa aataaataaa taaataaata aaaataaaaa attaaaatgt 88740 acaatagagt gtgtaaaacc aggaaatcta catcttgaca cttaactacc caagacgcaa 88800 ttggttcctc gtctgatttt taaaagaagt ttccactttc ttcggaaaat cacgacagtc 88860 cttgttctca atttctttgt ttttaagaag agaaatgttg tatgatttca cttatataaa 88920 ctacctagaa taggcaaatt cacagggata gaaaggtgga atggaggtga ccaaaggtgg 88980 aaaggaagga ggattgttca atgggtacaa catttctgtt tgggatgatg aagaatttct 89040 ggagatggac aatggtgatg gctgcacaac actgggaatg tgcttaatgc cattacttaa 89100 aaatggctaa aaatcatgca ttttatgtta tgtatattta caactttttt tttttttttt 89160 gagacagtgt cttgctctgt catccaggct ggatggcggt ggcatgatct cggctcattg 89220 caacctccac ctcccaggtt ctagcaatgc tcctgcctca gcctccccag tagctgggat 89280 tacaggtgtg tgccaccatg cctggctaat ttttgtattt tgagtagaga tggggttttg 89340 ccatgttggc caggctggtc tcgaactcct aacctcaagt gatctgccca cctcagcctc 89400 ccaaagtgct gggattacag gtgtgagcca ccatacctgc catatttaca acttttaaat 89460 cataggaaag aaaccactaa tgctttgaca actgtgagat tttgaatctc aactgtgaga 89520 ttatggtttg tggaaatttc tttatgtgat taaaaaagat actttttttg ccaaaaaatt 89580 tgttttcgct gtcatgcaag ttctcctggg taagcacctt tggtcttgtt ttgtgcatag 89640 catacagagc agcaattgta tattgctaaa gaaagcctgt tttttttttc ttgttaattt 89700 atttaagttc cttgtagatt ctggatatta ccctttgtca gatggatgga ttacaaaatt 89760 tttctcccat tctgtaggtt gcctgttcac tctgatgata gtttcttttg ctgtgcagaa 89820 gctctttagt ttaattagat cccatttgtc aattttggct tttgttgcca ttgcttttgt 89880 gttttagtca tgaagtcttt gcctatgctt atgtcctgaa tggtattgcc taggttttct 89940 tctagggttt ttatggtttt aggtcttatg tttaaatctt taatctgtct tgagttaatt 90000 tttgtataag gtataaggaa ggggtccagt ttcagttttc tgcatatggc tagccagttt 90060 tcccaatacc atttattaaa cggggaatcc tttccccata aggatatgaa cagacacttt 90120 tcaaaagaag acatttatgc agccaacaaa catatgaaaa aaacctcatt atcactggtc 90180 attagagaaa tgaaaatcaa aaccacaatg agatactatc tcacactagt cagaatggtt 90240 gttattaaaa agtaaaaata taacaggtac tggtgaagtt gcagagaaat aggaacacat 90300 atactgttgg tgggagtgta aattatttca accattgtgg aagacagtgt ggcgattcct 90360 caaggatcta gaactagaaa tgctatttga cccagcaatc ccattactgg gtatataccc 90420 aaaggattat aaatcattct actataaaga cacatgcaca cgtatgttta ttgcagcact 90480 attcacaata gcaaagactt ggaaccaacc caaatgtcca tcaatgtttg accgaataaa 90540 gaaaatgtgg cgcgtgaacc cgggaggcgg agcttgcagt gagccgagat cccgccactg 90600 cactccaccc tgggcgacag agcgagactc cgtctcaaaa aaaaaaaaaa aaaaaaagga 90660 aatgtggcac atatacacca tggaatacta tgcagccata aaaaagaatg agtttatgtc 90720 ctttgcaggg acatggatga agctggaaac catcattctc agcaaactaa cacagaaaca 90780 gaaaaccaaa cactgcatgt tctcactcac aagtgggtga gttccataat gagtgggtga 90840 gttccacaag ttccacaagt ttcacaagtg ggtgagttcc acaagttcta taatgagaac 90900 atatttgcac agggagggga acatcacaca ccagggcctg tcggggggtt gggggtcaag 90960 gggaagaata gcattaggag aaatatctaa tgtagatgac gagttgatgg gtgcagcaaa 91020 ccaccatgac acatgtatac ctatgtaacg aacctgcaca ttctgcacat gtatcccaga 91080 acttaaggta taataaaaaa gaaaaagaaa aagaaaaaaa accctgcctt ttgctttggc 91140 agtcatcatt ccttccatct tctcatgttt tcttatttaa ctcagtagtt ctcaattgac 91200 agcacaaaag aattactcag gagagttcaa aaaacaccta tggctgactc ccccaagatt 91260 ctgatttcct tggtgtgggg tagcctgggc atgaatatta tttaaaaact cctctcatga 91320 ttctaaggtg gtagccagga ttgaaaaatg ctggactttc aagtttttgt tttctttctt 91380 ttcttccaaa aaggtgaagc cctgacttgg gaagaattca aatgcgagtt aggcttatgt 91440 ttgatgtcac tgattcctaa agatcagtcc attgattctc ctcattctca ggagagcatt 91500 tggtgtcaaa atcacagccc aaaactctta ccctagttca gcatctaact ctcttcagtc 91560 ctgaaactgt ttttgtcact ctgtccatat aatcacagtg ttgtagaaat ttccagctaa 91620 acattgtctc aaactttttg tacctagttt taaatcaaaa tgtagtacaa aattattaaa 91680 tacaacgggc tttaaaatat tgagattttg gtgatctttt ttgtagaatg caaatactaa 91740 tgaaactaat tttttctttt gctttcaaac tatacatttc ttctaaaact tctttcaaag 91800 tagaatttca taagtggaag aacccttgaa gattatttta atagaattcc ttaattttag 91860 agatgaggaa actgagactc aaatatatta attaatttat ctaagtgtct tagtccattt 91920 tgtgctgcta taagagagca tacttgagac tgggtaattt atattgaaca gaaatttatt 91980 ggctcacgat tctggaggtt ggaaagtctg atatcaaggt gctggcatct ggcaagggcc 92040 ttctggatgt gtctacatgg tggaaggcgg aagggccaag aggtaaaatg tggctgaatt 92100 tgtgcttcta ttatggcatg aatcccatcc atgaaggtgg aggcctcatg gcctaatcat 92160 ttctcacagg caccaccttt taatactgtt acaatggcaa ttacatttca acatgagctt 92220 tggaggagac aaaaattcaa accatagcac tgaagttata caactagtta agaagagaga 92280 acctgagact gaaaccctga tgttttgact cccaatccag aatgtttgat cccctacatc 92340 ccaccgcttc gctgtttcca ttcctttctc ctgttttcat ctattttcac taagagggca 92400 agatatttgc taactgctac acacccaaat tgtataccag gcaggtcaga atgactctaa 92460 cattttattt aatgaggcag aataaaatat cttcctacta aacagtgaca agtgtttgtt 92520 ttaaaaaaaa gtattgtgca caaaaaaaaa aactactttc agcataggct atattttaca 92580 aaataaattt acagtgggaa ccacagagct atttagagtg tctggtataa atgattttat 92640 tgttactctg cttttttgaa aaagaagtgt gtgaagcaga ggtaagtagt actgaggaaa 92700 taataactaa aatactaagg acgagatgca catgggaaaa gttcttcatt aactgtaacg 92760 tggtggagaa atgtatgttc tagacaggtc aatcatggaa ttagaaaaag ttgggatctt 92820 ggattgttga gttcaaatcc ttagttttaa aactgaagac ttcaaatttt gattgactac 92880 agatcaatca acaacctgtt ggagttggaa acttgaatct gattctccat ccttgtttgg 92940 gatatgaaaa aaaggaagac atttaagagt atttttttat ttatgaaact aatgtatcat 93000 catgtaaaaa tatgaaatag aaagtgttaa aaattataaa gaaacaagaa tgtgttttta 93060 taatctcatt ttcttacttt acgtaagatg gtaagtctat tttggaatta attgttttta 93120 agaatagtat tataattcaa tgttagataa agatttattt aaccctttcc cctttaacaa 93180 gtgtttgggt tttttaagtt tgcttccaag ttttcggtaa atgatgcttc aatggatatc 93240 tctgtttgtt atcttagtat gtatcttaga ttaattcctc aagataaata tttaaaggta 93300 tggtatatgt aatattcttg atacatactt ccatatttcc ctccagaaat gtgtgcacct 93360 atttaaatgt gtgtggaggt gcacatttta acattcctca ttattctggc tgccttctat 93420 aaatcaagct accctggtat tatggctctc ctccagaaat ctaatcattt aaacacatga 93480 agtgaatgtg tgaatggaca attaagtgct ggccaaatgt ggaaaaatgt taagtgtaaa 93540 tcaaaggcaa ctgaaacgtt aaatacacct tccattcctc cgccacatcc atgctctttc 93600 ccatactcca catctgctca ctaaaattgg aaataaactg taatgaacca gaaatgtctg 93660 acttactggt gtgtttaggt gagttttatt gaaacactga ctgaccccac cactctaata 93720 ccatcacctt aatgtttgta tcttagatta attcctcaag ataaatattt aaacgtatgg 93780 tatatgtaat attattgata catacttcca tagttccagc aaccacttgt catcctgtgt 93840 cccccaagga cactgcaatg actgtcacag tgacttgtgc tcggttgagg agcaagtggt 93900 ggctgaaatc cagccccagt cagctcccca aaccaaacca cttttacaca gtgtctatgt 93960 gtaaagttgg tttgctttgg ggagattgat ccccataagg gatcagcacc agccctgtgt 94020 ctatctcttc ttctcctggg gagatgttgg ctattttgct agctggagaa gggcacgcaa 94080 tttgttgtca ggagacaggt tcttaagttc cattggtaca tgcagggcaa gacaggcaga 94140 gggaatctgt cactgctaca ggcacttcat aagcccaggt atagacgata attgaaatgg 94200 attgatttca tagtagtcta atacagagtg gtgctacaat ctctgtatgt gcctatttag 94260 aaaataactt catatttaat tcttcacttt acataaaaga tatgtgtatt aaatacacct 94320 tttattttag aacagtttta gattttagat ttaaattggg aagacagtag agatttccta 94380 tctaacccac acccagctcc cgtattagta actaacatct tgcattagta tggtatatta 94440 caattaatga accaatactg ttattttatt attaacttaa ttcatgcttt attccagttc 94500 ccttagtttc tacccaatgt ccgttttcta ttccagtatc ccatccagaa taccacatta 94560 cattctgttg ccatgagttt ctcagatttt ccatgttttt gatgaccttg acagttttga 94620 ggaatactgg tcaagcgttt tgtagaatgt acctcaactg agatttgtct catgtttttc 94680 tcatgattaa cttggtatta caggtgtttt gagaggaaga ccacagaaat gaaatgccat 94740 tcttattaca tcatatcaag catatattct aacaatatga tttatgacaa ctaatgttga 94800 ccttggccaa ctggctgggg tagtatttgt ctagtttctc ctctgtaaag tccttcctta 94860 ccccctttcc acactgtact ctttgaagga agtcactctg cacagctcac aatgaaggag 94920 tggggagcta tgcttcccct ctttgagagt tgtgtatgta cacaaattat ttggaattct 94980 tctgcatggg agatttgtct attctcccct atttatttat ttattgaatt atttatatca 95040 gtatagcttc atggatattt attttagact ttgggctaaa aaacaatact actttatttt 95100 attgttcaaa ttgttccagc ttctagaagt tatattttta tagagaagat atgtttttaa 95160 atataaaaac actttaaaaa aatgaagtca acaggataaa atatttttaa attttcctta 95220 atgggtgttc tttgtaccat gtttccatca aataacattc tgattgaaat ctaaaaatta 95280 gtgtttgtat tttaagtgct aagatcagag aaaaagtcac aagtttccca gactgagtta 95340 ggcaacatgt gactcagagt tataaggaat acctttccca ttcctgcatt gcaaccagtg 95400 ttacagttac agaagtgact agtgtaactt cccctcctgg gttccagctg ccaggactta 95460 ctttagttct tttaacatat ccttcccacc aaagataagt tttttgaaca gtttccccat 95520 gagtgctccc cccaccccaa cttgtgcctt ttattcatgt ctttataata tttattggtt 95580 ggctggtgca attgcagagg ttggcaagtc tgaaatttgt agagcaggcc agcaggctgg 95640 aaactcaggc aggagttaat gctacattct agggacattt ttttcttctc tggaaacttc 95700 agtttttgct gacaagcttt tcaactgatt gggcaaggcc cacccatgtt atgaggggga 95760 actgtacaat cagttgtcat ttaagccaat cagtcaactg atggttggtg tcaaccatat 95820 cttcagaata ccttcactac aacatctaga ctcatgtttg attaaataac tgggtgccat 95880 aaccttggca agttgacacc tgaaattggc catcacagtg accaagacag aaagtgtaat 95940 gagcaggaaa gcaccccagt gacaggacag tgaaagatga gcctggagac ggggagtggg 96000 aggagtgctt tgacagaatg gtcaagagag atggcatctg ggtggagata tgaaaagatg 96060 taaaagaagg gaaggaacca gttctgccaa gaatttatac ttctacaatt tcccagatga 96120 tattgatgct gttgccctgg agcccatact ttgagaacca cagagtaagg gtatacctct 96180 gttattatcc aatgaatcct gagaaagccc attaatatct cagtgtgacc attttttctc 96240 aaaattccta cctcacatgc tctgaggggc tggcagcttt tctgggaagg taaaatctca 96300 agagggaggc tttgaatgat tccaggacaa agtgaagata acatactacc gcaggtaaag 96360 tctaggttta cttggaggtg gctcaaaaca caaatcctgt caattttaat gacacatgag 96420 gccatgactc tgggtcgtca ctctgggcaa gccattgaac ccattagaac ctcagttttc 96480 ccatctgtac aaaaagaggt gataatgggt aagcaatcct ggactgcatt gtggtagtgc 96540 catcaagcaa tgagatttgt caggaaggaa gtgtgattca agtacaggca ctttgttatc 96600 tgatgcctgt gtgttgagtg tgaaggaggg gttaattatt cctctattca tgtcctttct 96660 attctcaaaa tttcttatgt gggaggaaaa tcttggtgcg gtaaagatca cagccaccct 96720 ggggtcagac agaggactgt gtcaagcttg gtaagcgtca ccattcaggt gagtgggaaa 96780 gagactgaac cccattaaac cagatgacct ccaaggccct gcccgcccca acatctgagg 96840 gctgcctggc ttgtctgcac agggtgctca cagtactcct gactttgaca taattttaac 96900 attaaagtca caaggatgcc ctggatcaca actgctggag aagagatggt agtgggattt 96960 gtttcccagg agactttctg attctagtgg ggccaggacc aacctccaaa ataagaggtc 97020 tttgcaactg ctgcgagcct cctggcacct ctaccctcta gcgagaggct gcctctcctg 97080 ccccaccccg gtttcaagca cgctgcaggg caggaactca ctgtgctggc aaaggtgagc 97140 tggagacctg gcacggcata aagctttttt aactgaccct ttttaatttc atcttccctg 97200 gacttaatct agagagtcat tgatgaaaca aacatgccat tttctcccga tttcacgctt 97260 ttaaatgtca acaacaaaca aacgtttata tacacaaatg ttgctgaagg agacttttgg 97320 ctttagacaa gggtaaaaac tgaacctctt agtgtgactt tggttgattt tttaaaaaat 97380 ctgtaatttg acatataaag aattattaag actttttttt tttttctggt aggcattgaa 97440 tgtgtccttg aaaagaaaaa aaatatgctc agtttcaatc ttctgtctat gggtagctag 97500 ttatcccagc cttagttatt gaataaggag tcttttcacc attgcttatt ttattttact 97560 ttttgagatg gggtcttgct ctgtcaccca ggctggagtg cagtggcacg attttggctc 97620 actgcaacct ccgcctccca ggttcaagcg attcccctgc ctcagtctcc caagtagttt 97680 ggattacaca tgtgcaccac cacacctggc taatttttgt attttgatag agacagggtt 97740 tcaccaagtt ggccaggctg gtcgtgaact cctgacctca gttgatccac cccacttggc 97800 ctcccaaagt actgggatta caggcatgag ccaccgtgcc tggctgcatt gcttattttt 97860 gtcagctttg tcaaagatca gatagttgta ggtgtgtggt cttatttctg ggctctctat 97920 tctgttccat cagtctatgt gtctgtttgt gtatcagtgc catgttgttt tggttattgt 97980 agccctgtag tatggtttga agttggataa catgatgctt ccagctttgt tctttttgct 98040 tagattgtct tggctatttg ggatcttttt ttggttccat atgaatttta aaatagtttt 98100 tttctagttc tgtgaagtat gtcactggta gtttgatagg aatagcattg aatctataag 98160 ttgctttgag cagtatggcc cttttattga tattgattct tcctattcat gagcatggaa 98220 tgttttttcc atttgtttgt gtcatctctg atttatttga gcagggtttt gtagttcttc 98280 ttgtagagaa tttcacctcc cgggttagct gtattcctag gtgttttatt tcttttgtgg 98340 caattgtgaa tgggattgtg ttcctgattt ggctctttgc ttgactattt ttggtgtata 98400 ggaaggctaa gtgatttctg tatgttgatt ttgtgtcctg agagtttgct gaagttgttt 98460 atcagctgaa ggagcttttg ggccaacact atggggtttt ctaaatatag ggacatgtca 98520 tctgcaaata gggatagttt gactacctct ctttctattt ggatgtgcta tatttctttc 98580 tcttgcctga ttgctctggc caggacttct aatactatgt tgaataggag tggtgagaga 98640 gggcatcatt ttcttgtaac tggacccctt ccttacacca tatataaaaa ctaactcaag 98700 atggattaaa gacttaaatg aaaagcccaa aactctaaga accctggaag actactgagg 98760 caataccatc ttagacatag gaatgggcaa aaatttcatg atgaagatga caaaagcaat 98820 tgcaacaaaa gcagaaattg agaaatgaga tctaattata ctaaagagct tctatataac 98880 aaataaaact atcaacagag taaacagaca acctacagaa tgggagaaaa tttttgcaaa 98940 ctatgcgtct aaccaaggtc tactatccag catctataag gaacttaaat ttacaagaaa 99000 aaaacaacct cattaaaaag caggcaaagg gcatgaacag acacttttca acagaagaca 99060 tacatgtggc caacaagcat atgaaaaaag ctcagcatca ctgatcatta gagaaatgca 99120 aatcaaaacc acaatgagat accatctcac accaatcaga gtggttgtta ttaaaaagtc 99180 aaaatataat agatgctggt gaagttgcag agaaatggga acacttatat aatgttggtg 99240 ggagtgtaaa ttagttcaat cattgtgaaa aacagtatga tgattcctca aagacctaaa 99300 aatacaacta ccattcaacc tagcaattcc atgactgggt atatacccaa atggatataa 99360 attgttctat cataacgaca catacatgca tatgttcatt gcagcactat tcacaatagc 99420 aaagacatgg aatcaatcta aatgcccatt gatggtagac tggataaaga aaatgtggta 99480 catatacatg atagaatact atgcagccac caaaaagaat gagatcatgt ccttttcagg 99540 aacatggaag gagctggagg ccattatcct tagcaaacta atgcaggaac agaaaaccta 99600 atactgcatg ttctcacttg taagtgggag ctacatgatt agaattcatg gacacataga 99660 gaggaataac agacactggg gcctatcaga gggtggaggg tggaaggagg gagaggatca 99720 ggaaaaataa ctaatgggta ctaggcttaa tacctgggtg atgaaataat ctgtacaaca 99780 aacccccatg acacaagttt acctatgaaa caaacctgca cgtgtacccc tgaacttaaa 99840 ataaaagtta aaaaaaaacc ccaaaaggtg aagtgttggt gaggatgtgg agaaaaggga 99900 acccttatta cacaattagt gggaatgtaa attagtgcag ccattttgga aaatagccaa 99960 ggaaaatttt tttattgagt cagatgatgt taccttacag caatagcttc caaaggggat 100020 gtcctgaata gtagaacttc tctttacatt ttcaaacctc tttttacttt ctgattttga 100080 gtttcataat gaacatgtat caatacaata gcacactatg tattttataa atgaacaaat 100140 atgggaaaaa taagatatgt tcactttcct ggctgaccct agttagtcta aactatcagt 100200 tataggatcc atttgttcta aatattgaag gcattgttgg gggcagtggg gagggtgaat 100260 gatagacgca aattccttga aggaatagaa atgtgactac tatgctgaaa agcaggaccc 100320 atggagtata aatagagtat tcactgtgct tttacatttg tttccctgga ggaaacgtaa 100380 aacaaatctc aagactttct ggtcatttct aagtcataaa cggccactag tcactaattt 100440 atataaccag cccaatgtaa atatcaaacg tgtgagtttc atttcatctc acaactcctc 100500 ccctttccca gttctggccc catacaagcc cgctgcctgc agtgtaatgg aggaagatgg 100560 tttctttttc cttccctccc atttatttgt ctttgtgcat cttaaagcca gcctgaattt 100620 ctactcccta caaggttgaa gtgggtgggt caggaggtgg ggagagagct aaggaacgtt 100680 ggcgtgagtt gttgttgtgt ttgagtctgg aaggtgttgg gagctgcccc ccctcactca 100740 gggcctcatt tatgggctct tcggataacc cccatgctct agcactggga tcttgccctg 100800 tggatccctc catgcaggtg gcaccacacc ctctggctgg ttgtgatggg ccttctcagc 100860 tttgagaatt agcaacacac ttcctattga agtcatctgt ccctgtgggt agcccacttg 100920 ggctggatgc aaactgaacc tgcactgatt ctctcttgca tgtggcccac atgagctcca 100980 ttttcctccg caaactttgg gtgcacagcc ccacgacgac acagacagct tttcttgcgt 101040 gccaccaaag tggtgggcca gagttctctt atccttaaga ttttcaggtg tcaccacgtc 101100 caccaattct tggcagacat gaatcaatac ttccaagggt tttggtgaag cccttttccc 101160 tgggctgcag atgagggcag ccatgtcctg tctcttccac ctgttgtgga aggggttcat 101220 ggcaaacatc ttcgaacatc ctctaatttc ccaattcttg atcctttcgt atgcttgatg 101280 tgtgagagag aagagagaag agagaaacgc ttcttgctgc tttttttttt tttaatccca 101340 catggtgacc ttagacttta ctttggaatg tgccatttaa tatctgggga cctcagccca 101400 acacagggac taaatagctc tgttttaaca ttttgtttat atacacacat tcatttgacc 101460 aaatgaacat gttccagctt ttttaaccct tgcccagcaa atcacttaat tcagttaata 101520 aaaagactaa aataatgagg ccaaccttat tggccacgaa catctgttgg gtattcctaa 101580 attgatccct gagttaatct ccacctttaa ggagtttata attttatttg gcaaattgat 101640 gttataatga aattcctggg catgaaaaaa acctaactat gtaatgttgg atagtgtgag 101700 ttttcccaaa agtaccagta taagcaataa atgctataac tgatcatgaa ttgtttacag 101760 tgattgagta gaatcattgc atctggtcat gaatagaaag agcacctccc agacggctgg 101820 tctgctgcca ggtgtgcagt tttaggggtc tccacactca ttctattcac atcttttgac 101880 tttatcagct gtgtggtgga tctgtggtta caggctgatg tggtttggct gtgacctcgc 101940 tcaaatctca tcttgaattg tagctcccat aattcccacg tgtcatggga gggatccagt 102000 cggaggtaat tgaatcacgg gggcgggtct ctcccgtgct gttctcgtgg taatgaataa 102060 gtctcacgag atctgatggt tttataaatg ggagttctct ttcacgagct ctcttgcctg 102120 ccgccatgta agaagcgcct ttgctcttcc tttgtcttct gccatgattg tgaggccttc 102180 ccagccatgt ggaactgtga gtccattaaa cctctttcct ttataaatta cccagtcttg 102240 gatatgtctt tattagcagt gtgaaaatgg actaatacat gagccacatt gttacagagt 102300 ttctgaaggt cattaagaga agtccatgct gtgggctgag ctgggactca agaatctcaa 102360 aggagagcca gtgcaatcaa cacgaagggc ccatcttgaa ctcctaaggc agggcagagc 102420 tgggtcttat ggagacatgt ggctttcagg taatccagtg agcacctgtg ttttcctcct 102480 ataattcttg aggaatggat attgttctat atttcagata gtataataat aaatacctgg 102540 aaaatactgt atgaccccaa acaacaggta aaatgtcaaa aaaaaccttt tatctacaca 102600 aagttagaca acaaattcaa ataatcttat ccgtttattc attctcttcc aatacaatca 102660 tgtatcattt aatgatgggg atgagtttgg aggaaggtgt tgttaggaga ttttgtcatg 102720 gtgcaaacat catcaagtat acttatgcca acctcagtgg tatagcctac tacacatcta 102780 ggcttggata gtacagcctg ttgctcctag gctataaacc tgtacagcat gttactgtcc 102840 tgaatactgc ggcaactata aaataatggt aagtatttgt atatctaaac acacttcaac 102900 atagaaaagg cacagtgaaa atatggtata agagataaaa aatggtccac ctgtacaagg 102960 cacttgccag aatggagctt gcaggactgg aagttgctct gggagagtca gcgaatggct 103020 gatgagtgaa tgtgaaggcc tagggcatta ttgtatgcta ctgtaaactt tataaacact 103080 gtgcacttag gatacactaa atttattaaa aatttttctt tcttcaatca ataataagtg 103140 aacattagct tactgtattt ttttttttac tttataaact ttaatttttt tttagagata 103200 gggtcttgct ctgttggcca ggctggagtg cagtggcaca atcatagttc actacaacat 103260 tgaactccta ggcttaagca atcctcacac ctcagcctcc tgggtagctg gtactgcaga 103320 cgtacactac tgcacccagc taatttttaa attttttgta gcgactgggt tctgctatgt 103380 tgaccaggct ggtcttgaac tcctgactca agcaatcctc ctgcctcagc ctcccagcat 103440 gctgggatta taggtgtgag ctactgcact tggcctaaac tctaattttt aaaatcttct 103500 tgactgtttt ataataacac ttagtttgaa acacaaacac attgtacagc tgtacaaaaa 103560 tgttttcttt ctttacatcc ttattctata agcttttttc tgtttaagtt tttaaaaatg 103620 ttttagtctg agtgcggggg ctcacgcctg taatcctagc actttgggag gccgaggcgg 103680 gcagatcatg aggtcaggag atcgagacca tcctggctaa cacggtgaaa ccctgtctct 103740 actaaaaata caaaaaaatt agccgggcat ggtggtgtgc acctgcagtc ccagctactc 103800 gggcggctga ggcaggagaa tggcatgaac ccaggaggcg gagcttgcag tgagctgagt 103860 ttgcaccact gcactccagc ctgggcgaca gaacgagact ctatctcaaa aaaaaaaaaa 103920 aaagttttaa acctttttaa aaaatcaaag tcacagacac atgcattagc ctaggcctac 103980 ccagggtcag gatcatcaat gtcactgtct tccccttcca catcttgtcc cactggaaag 104040 tcctcaggga cagtaacacc cctggagctg tcatctcctc tgataataat atgggcttct 104100 ggaagacctc cagaaggacc tgcctcctgc ctaatgctgt tttacaggta atattttttt 104160 ctagtagaag gagtacacta aaataatgat aaaaactgta gtaaagtaaa tatataaatt 104220 agtcatatag tcatttatta tcataatcat tatgtactgt acataattgt attgccagac 104280 ttttatacaa ctggtggcac aataggtttg cttacaccag catcaccaca cacgtgagta 104340 atgtgttgtg ctgtgacatt aggacagcta caatgtcagg aggcaatagg aatttttcag 104400 ctccattata accttacaag accactgtca tatctgcagt acaaaacatc attatgtggt 104460 gcatgactat atttactgag caccaaatat gtgcccaggc agtgtgctag gggctggaag 104520 tgacctcgaa gtctagtaaa aaaaccacaa cagtaaaaca atatgtgtaa ttcaaagtga 104580 catatcctgt aatagctggt tgcctacctg ctccccagag agaaattaaa cctgcttgct 104640 taacttatta attttaaatt catgtacttg caatataaaa acatatttta aaacatatta 104700 ggagaatagg atgtcttctg tagtgatagg ctatttaatg ttctcttcac tgtgttctaa 104760 aaaaatcgtg atcgagtgta acaaaatggg gaagggaggg ttagcataaa ctctcctttg 104820 atgtctatgc tgtggatcag aaaactcatg aatatgttaa caactggatt ttctcctaat 104880 atgaaaacaa ctctttggct tcttttgcaa atgtgaaaag ttaaccataa atataagacc 104940 ttttctttcc actaaaacta gggcacaatc attgttttcc tcttattgga gtccaaatgg 105000 gtttccataa tcttcagatc tagtagttgt atttatcgat gacataaatg gaaagactaa 105060 aagataaagt taagaaaaat tcagtggttt atggcttcaa ctctactgat aattttgtat 105120 ataaagggat cctaaattag actgtacaca catttgccat ttgagttcca agcattttag 105180 caatagatca aaagatctta atgcctgata gttgaaagat tacttccaaa ttttttttat 105240 ttttgtgaaa gccaaagtcc ttttctcaac atgacagtca caattttgtc aacaatctac 105300 ccgttattta caaaggttta aaatctgata atagatattt acttggacta tacaatgtct 105360 cagtgggagc aatagatggt ttacaatggg tctgaaaatg ttgcaaatag tcaaaactgg 105420 cattgcaaca attcatttcc aaaaacacac tagactcgtg agtttttggt ttttaagttt 105480 atatagcttg cttctggtgt taacgttctc cacacctaag gtgccaacat gcatggctac 105540 tctttgtccc cagagaaaca ttgctaattt gtaccaaatt tcaatgatgt gtcaagcaaa 105600 ctgtcatttt ggaatgatag taagcacgcc ttcaacaaca gctctttatt tcgtccaaaa 105660 cctttgggcc acacaattct gacctttatc acactctcag tacctttcat tcattattag 105720 cttgtgcttc tggggccccg ggaattgtca actatggtca aaataatgga gcaaaatagc 105780 aagaagaact tgcgtttcct atatcattgc atttaatctt tgcaacaact ctttgaggtg 105840 gaaattgccc caattttata gattcagctt aaagaccttg atttgtccaa gatcacacaa 105900 ccactaggag gtataatgtt caaataaaaa tgtctgaaaa gagctgggtg tggtgggtca 105960 tgcctgtaat cccagcacgt tgggaggctg aggtgggggg atcacctgag gtcaggagtt 106020 tgaaaccagc ctgggcaaca tggcgaaacc ccgcctctac taaaaataca aaaattagct 106080 gggtgtggtg gtgcatacat gtaatcccag ctacttggga gactgaggca cgagaattga 106140 atgaaccctg tgaggcagag gttgcagtga gctgaaatcg caccactgca ctccagccca 106200 ggcggcagag tgagactcca tctcaaaaaa aaaaaaaaaa aaaaatctgg aaagatagat 106260 tacttggcct caatcatagt aaaaaagtgt cagttaaaac tgcatggaga gatactattt 106320 tgaaaagcat caaaaagttc gaagatccat catatttgta aggctatggg agtttaaatt 106380 gtacaggcgt tatgaaggca tttggttaca tctaccaaaa ttaacaccgc acatatttac 106440 tcatgtgcaa attgacttat gtacaaattt actaattgta gcattgttga taattgtaaa 106500 atattaggaa cacacctaat tgccattaat ggggaactgg taaaataaac tagaattcct 106560 ctgtgcatgg aatactatgc agtcatcaaa aatgacgaag atgtggccgg gtgcggtggc 106620 tcacgcctgt aatccagcac tttgggaggc cgaggtgggc ggatcatgag gtcaggagat 106680 caaaatcatc ctggctaaca cagtgaaacc ccatctcttc taaaaatacc aaaaaaaaaa 106740 aaccaaaaca caattagccg ggcatggtgg cgggtgcctg tagtcccagc tactcgggag 106800 gctgaggcag gagaatggcg tgaacccagg aggcggagct tgcagtgagc cgagattggg 106860 ccactgcacg ccagcctggg tgacagagtg agactccgtc tcaaaaaaaa aaaaaagaaa 106920 acagaacaaa acaaaaaatg aggaagatgt ttatttagtg aaatagaaag atatccaaga 106980 tatgttgcta ataaaaacaa aaaaaaacac atggcacaaa taaggtgcat gttactatct 107040 gggtctttta aaaaggggtg tggaagaatg tgtgtgtgtg ttttcttcaa tatgtgtaga 107100 atatctctgg aaggaaattt aaaaactggc gacctcagct gtctccagag agggaaaatt 107160 ggtgggttgc aggcagaggt gaaagatttt cccactatga ctttgaaaat atcttttcaa 107220 gtttaaagca ccaactgcat tatatatcaa gagtaaataa aatacaattt taaaatgaaa 107280 tggcatttgt aaaacacttg atagatgttc agttaacagc catcaggatt tattagtaat 107340 tgtggttttt gccattaaaa gtaattttaa aagtaatggt tttgccatta gttttaatga 107400 caaaaaccac aattagtttt gcaccaacca aataccttac gcttctggtg agggctcaga 107460 agagagatca taagtaaaga acactagaaa ggatgtttaa tattatttcc ctttttaaaa 107520 ctggtggttg tcaaagcagt ctgaaggaaa agtctccaga actggtgatc atgttcacat 107580 agcagtagtt tggagtcaac agaaatcatc ttcaccatca acctagctcc gaaagaggcc 107640 gagccaatct agttcccttg gccaaccacc ttcctcccaa cctatacgtt ggggtgatcc 107700 actacaaagc tctcaagagt atacacaatg ctactacagt cattgtgagt gagatctgaa 107760 gggagcatag gctaggactc atgagattat agttcagagt ttctactgta attcctttca 107820 gcaaagtgaa gagcatgtca ctggggttac aagtgttact ggctacttag ctagtgctag 107880 attacccaaa aaagtaaccg ggtctcatgg gcagaggtgg gaaagtctgt taagcacata 107940 gtgaaggatg aatctgggct gattggaaaa catttgtttg aatgaatgta gcatttattt 108000 ccaagaataa gcatgtccag actgattgag caagagttat atttagttca gtcgttctga 108060 tgtccatttt gagaaagcta aaccagcatg ccagaagggg tcaaagatca cattttgcat 108120 gaaagaaaag ccaatggaaa tgggactgtt agacttaaac ttttgggtat tttacactag 108180 gacttagaaa ggactttatt cctttttata ttttctgtct ctagcattgc aagtagcaac 108240 agagtgaatt tttggtattt ggaatactct ctcctcattt ttcctttggg aaaatcatta 108300 gcctatttga tttgactgct gttgaatatg ttccatgaca tccataagtc taccttcagg 108360 cattgcttgt gcttgtttat tacatatgat taattgctta cataagaaca atgatgatcc 108420 ctgcaggggg aggagggatg tgaagaacaa cttacttagg cattccaggg gctaacaagg 108480 gatggtttga tacagctcat tcttgttttg aatcttcatg cctcttgaga aagaaaggag 108540 cagaatatgc tttgcatggc gctatgtcct cccaggtcct atgttttctt ttttgtattt 108600 tatcagttct ctacgtaagg attttctcag tttaatataa tttccatttt taaaattcaa 108660 atacctacat atgaggtggg aaaggaaatt aatcagatgc attcctataa actgcagact 108720 taaattaaga ccttgagcaa actggcattt tgatgacttg aggattcagt gggtgggaca 108780 gttgtacatc ttgaactctg ggtacactgc cgaaagcgag gcctgagaag gctgtgttga 108840 ggaaggagtg tcagtgactg agcctgttgg aaagggaggc tgagagagat gaggacacat 108900 acgtaaggga gaacacattg gctggccagg tgtttttttt tctgctgtgg attttgatta 108960 gaattctggg tctcattaag tgacccatgt tgaatagaga ttggataggg ctggcttgga 109020 aagccctcag tgaagagatg aactcgacag catgataagg aagtagatgc aaattcagga 109080 caggaaatgg agaagggcag ggtgagaaaa gggaacaaat ttacaatttg tgccattagc 109140 catttattag aatttggtat aagaatttgt ggaattattg tttccttctg gatttatggt 109200 acaaaaacct actgacaagt gtcactaaaa gtgatgtctt tattcaatta tcaaccaaaa 109260 gttttacact aaattctttt gagtctttga atgtttatgt tatttccaat aatctttcca 109320 gttcttttaa aaggctgatt tttaggaagg ctagcacttt ttgatcacag aatagtttcc 109380 ccaatgagta tgatagcttc aatatctttc aaattagatt cttttggaaa ttgaactgtg 109440 tcaaatcaaa taaaacaagt agggtttttt gctgttattg ttgaaggtat tatatttgca 109500 agtttgtaca atttagcaga tataggaaag gtctaatttt tttctttagc tagaatgttc 109560 agttcaaatt atacagatat aagcatgaga cctaaatgaa ctctcttctg atgagtaatg 109620 aatggaaggt agattactca tttcttcatg ttcaaaaaac aaattatgtc tctgaacaca 109680 gttgtttcaa tgtttttaac ttatgttctc aagctcttcc catttcttta tcagtgattt 109740 gggaatgtga aggcagtctt gttgtagttt ccaaagattt aggcattttt gagactctaa 109800 gaatagttca ttaagccacc aattagtccc ttaattttat ttaagctgag caagcaaggc 109860 ccacactaaa agtcagaaga atgcggcatc tacccagaga ggctgagggt gggatagaaa 109920 gaaggaggca ctccaagttt ggagacacag attctattcc agttcctcaa gctgcatgac 109980 cttcagcaag tctcctgtgt tgttcaggac cccagtttct ttataagtgc aatgaagagt 110040 ttggactcaa caacttataa agaaacattc attctaattg tctattgtgt gaaaagaatg 110100 tgagttgttc tagaaaatat gaatctgctc cccaattgtc ctccaagctc tggttctaaa 110160 tttcagttat tatagttact tctttcgagg taaatcattg aggaagtcag ttaatgcaga 110220 gatgatgtct ggaaggagtt tacaagttca ttgttcaaat agtatttgtt gggggccaac 110280 tacaactaca catcagggat tgtgctcaca ttggactagt gtctttggaa aacagagtcc 110340 ttgtgtgccc tttttgaatt tacaggccaa cttggggaag cagagagaca aataggaaat 110400 ccaacagcat gataagtagt ataatgagaa tgtttaggga gatacgagca tttataggag 110460 tagcactcaa caggaaatca aggaaggctt cctggtggct atgatgtctc aagggagact 110520 tgaagcatga gtaggagtat gtcagatgaa aagggatggg aggaagattt caggtagggt 110580 aatttgcata cgtgaatatt tagacccaga gaaagtccag agggactgag gaacttaaaa 110640 gaaatccagt atgggaggag catagtacct gttggggagg gtggggactc ttgataaatg 110700 aggatagtaa ttcaagttct ttggctcttg agttactttt ggacaagttg agcttcaagt 110760 agctagtaca taggaggagc ttaataaata tttattgaat gaatgaacat gtaagtaaaa 110820 atgtctaata ggtacctggc aaagtggact tcctagtcag gaaagagagg ttggttggag 110880 atttctattt tgaaattttc aatgtatata tgaaagtaaa aacacaagga gtggttgtga 110940 tcatccagga gaaggtatgc agaggaggga agagggtcta ggggctgaat cctggggtac 111000 ccacacctga gaggagggag aggaagaggg gctctcagaa gagcctgagc aggaagggcc 111060 attgtaatag gactaaacac taagcccctg aagtcagctc tctgggggca gaggtttttg 111120 ttctgtttat tttgggatgc ctgctgttga ccagattatg ctcccctacc cacccaaatt 111180 cacatattga agccctaaca ctcaatgtga ctgtatctgg agatagggtc tttgggaggt 111240 aattatggtt aaatgatgtt ttaaggctgg gaccctactc tgataggact gtggccttat 111300 aaaaagagct ctctcttttt ctgtcctcct ccttctacct cctccaggac ccaccccaac 111360 cccacactga gaaaataaat cgctgttgtt taaatcaccc agtctatggt attttgttac 111420 agtagcctga gctgaccaaa acagttctcc gcacttagaa atggtcctgg taaatacagc 111480 taatcaatat ttttttgagt gaattgaatg aatgagtcat tcactggcat gcttataaat 111540 gcattactcc ctccacagtg tgattgtcat tgagcaggtt gggagaaggg aggagctctc 111600 gcaaacatgg aagtcctggg tgcttaggga gaatgggaag gtgccgtggt cacaaaatcg 111660 gaagaaagag ctgaaaggct gaaaggctga aaatgctaaa ctgctcaaat ctcctctgtc 111720 tttttttaaa aaaaatcatt tggctaggct ggctctgaaa ttggggatgg ttcttggttg 111780 attatgtggt gtgtgtgtgt gtgtgtgtgt gtgtgtgtaa aggcccttct taacattaga 111840 taggactatc tgaatctaag tgaatttagg cacaatctag atattgctct tcatagagaa 111900 ataatactct aagctggcaa tgaaattcct caagtaaaca acagataaag ggaaggagag 111960 ggacacagtg taacaataat tggaataatt ggaattcttg tatcactcat ggcacttaca 112020 gtgaaagtac tttctacatt gtcttctatt acatgcaaca taggtacatt atataaaaag 112080 atcctaaaat attgttaaaa gaaattttcc cagaaaatgt aagataaaag ttactaaatt 112140 ctattaagct tgcaagttaa atccaaatca ttcattgact cataatcaag aacagtcatg 112200 ctgcctgaca accaaaaaat tcaaactgtc ttcatcaagt cctgggtggg aagccaggaa 112260 atgggatctg agatcacagg ctttgtgaga gtcagggtct ttggcgtgat tcttggtcac 112320 aaatcatgca tttttttcct tggagagata gtgggaaaga aaaggctgtt taaaaacatg 112380 ttaaagaata ctgattccat ttgacttctt gttaatgtgt acccttgcag acttgggtaa 112440 aacttgatca tgttaaaagc cattgtactt aaagattcat gactagagtg ttaggacaat 112500 tctgtggcct tgggggtccc attgcagcaa gaagagtctg actgagaaga ggatagctcc 112560 gtcctttgat gcctagtaac ctgcatgccc agcactttgc tggctgggcc attggtagga 112620 aatgcggtac atgcacttca atctgtaaga gatcatggtc catagagatc atagatttat 112680 tttgccacct ggcccagatg gtgatagaag tcaggacaat ggttgcctag aggggttggg 112740 agtttattag aatgggacac aaagggaaat ttctggggtg atggaaatac tctatacttt 112800 cattgggatg attgttacat ggacatatcc atctgtcaaa ttcatcaaat ggtatgcttt 112860 agatacatgt atttcattgt atataaattt tgcctcaaga aacaaaaact caaggtcagg 112920 tgaaaaaagt ccaggagcta atcaaaaacc cttaaaataa gtgaccaaac tatttgtgaa 112980 aatgagcaga aacttaaagg gaaattcttt gttatttttc cacattagag gaaaattgat 113040 ggtatcagat aaatgctcaa aaataagctt ccaaacagag catttataat cagtacaata 113100 ataagtttga acacagacaa accttcatgt ctcagagtga aggaaccatt tctagtagta 113160 taagctatta cggagatagt tccacattta ttttctttca tgtttctttt ggaggaataa 113220 tgtttttgta aatgtaaaat gcttttaatg gagctagaga agaagctatg tttggtcata 113280 gtattatctg cttgcgaact aaaaattcag agctctcttg tgaatcatgc tgccaagaat 113340 tgcagactta agcctcaaga ttgtacgaat ttaaattttg actttatggc ctcagttggc 113400 atgaagatac aaagataatc ttctagcaaa aacagttttg aaagaccggg cgtgatggct 113460 catgcctata atcccagcac tttgggaggt tgaggcgggt ggatcacctg tggtcaggag 113520 ttcaggacca gcctggccaa catggtgaaa tcctgtctca actaaacata caaaaaaatt 113580 agctgggtgt ggtggcggac acctgtaatc ccagctactt agggaggctg aggcaggaga 113640 atcgcttgaa cccaggaggc agaggttgca gtgagccgag atcacaccag tgtactccag 113700 cctgggtgac aaaagtgaaa ctctgtctca aaaaaaaaaa aaaatggtag aatgtcacat 113760 ggaaagttaa cttttagaga tagtaatcca gacacctata atattacatt gtccttttaa 113820 gtatctatat caataaatta accaacattt gttgacttaa catggccagg gacagtgctg 113880 ggttctcata attcccaagt aattctagcc agaccttgtc ctcaaggagc ttatgagcag 113940 catgaggaga taaaaaacag ataaataact ctaattcagg aagaatttga taaatgcatg 114000 ataactacta ctagaattca gaggagagga aattttcttt gaatagagac taaaggaagg 114060 aataatgaat gtggtagcat ttgggctgga cctattacaa gaggcatgct ttcccctgac 114120 aagccaagaa agtggggatt taaggtagaa gaaaagaaaa gccttgagtt cttggagtat 114180 taaaattttg cttggctgaa gcataggtta cagtcggagg agatggacta ggaaggatcg 114240 ttatgggcag agaggaagcc ctgaactcat gggggaagct atgatttggg ttaaagacag 114300 agctgggtca tgtcaagatg gatcctgaag cagtaaaaaa aaatccaaga aagtaaacag 114360 gttgcagggt ttaggatgaa gtccgggagg aaagggcaga gtggtcctta ggaggccgtt 114420 aggacaggta aggtaatggg tctcaaaggg agtggccgaa atgcaatgga aaaagagaga 114480 ttgtaaagct agaaggctta ggaattgcct cttgattagg tgtggaaggc aagggaaaat 114540 cagccctcga agaagacagt gagattttaa tctgggtggc tggagagaca gtgatgctgg 114600 gcacagacac ggggaagttg agaggaacac catgtttgag aatggtgact catatttgaa 114660 caagcctgca atgcccagca gaccgctgga aaagtggggc tggagacaca ttcaacggag 114720 gagccagatc aatctttacc cttcttcacc tgagagagcc agtaagtcac ggctggaacg 114780 tgtgtgtcca gcaggagagg gtagggaggg aagccaagag agctgggagc ccgagtgaag 114840 tttttgccaa aggcagaaga ggaaagtcgg cgtagcacag tatactttcc cacccatgct 114900 caccaagccc agggacaagg ctcaccaaga tgagtttgga agagaatgct ggagagaaag 114960 tggttaagaa aactgccttt actgaacttc ttgggctaac tttgattgta agtctctgaa 115020 caatcaaagc ctgtgaggag acagctaacc ttcttattct tcctatgtca atagtgaaca 115080 attgcagatc ccctttcctt tccttctcct ttcccctgtt cctctctcct ccctccctga 115140 atactcttgc ttttttctgg gactggtcta gagcatgggt ggccattgtt gacctacagg 115200 aggcaccact gtcaccaaca aagggtaaca gtctttcttt tcaatattta tttatatcca 115260 gtatttattt tcaatactga ctatggagag agctctcctg tgctcaaaca ctgcaatact 115320 gggggtcttt caaagcacaa aaacatatat ttgcatgatg gcatcattaa catttttatg 115380 gctttctatt tcttttttgt actggtctca agagccactc ataaatctct cagtaactgc 115440 atagtgtccc agggccagag accggccact cctggcattg tgattagagt catttaatat 115500 ccaaggtggt gactaatgtc tggcaacaaa gcctccattg ggtgtcatgt gtcctgggac 115560 cctgagcgtg ggcactctag gagcacctca gtattgcgtg ttagtactat ggccgagaga 115620 atagttgaga aagtggtcaa gaggtggatc catgtgaacg ccactgggaa atgagagacc 115680 tcgttcccaa tcacggtcag tgcaactcga aagcctaaaa tcagtttaaa acaaaggtat 115740 ctacctttat cttatgttca tatcctaggc ttttaataat acgtattttt cacatgttta 115800 cagaaagcag tcaactgagc tattcatgga aaggtttgtg ggtttggtta acgaagtgga 115860 ggagtattac atttcagctg gaaacacatc cctagaatgc caaaacattt attccaaagt 115920 ctggtttcct ggtgcaatcg gaggcatggc aatgcctctg ttcagagact gggggctagg 115980 gccagtaagg catttgatcc acatgtatcc cagaaggctt ttattgttaa attatattct 116040 ttcggaaaaa ccacccatgt cctattttgt aaacttgata tccatacact tttgactggc 116100 attctatttt agccgtaaga ctatgattca cagcaagcct gtttttcctc ttgcttgggg 116160 tggcagcaga aagcataggg tactttccag cctccaaggg taggggcaaa ggggctgggg 116220 tttctcctcc ccagtacagc tttctctggc tgtgccacac tgctccctgt gagcagacag 116280 caagtctccc ctcactcccc actgccattc atccagcgct gtgcagtagc ccagctgcgt 116340 gtctgccggg aggggctgcc aagtgccctg cctactggct gcttcccgaa tccctgccat 116400 tccacgcaca aacacatcca cacactctct ctgcctagtt cacacactga gccactcgca 116460 catgcgagca cattccttcc ttccttctca ctctctcggc ccttgacttc tacaagccca 116520 tggaacattt ctggaaagac gttcttgatc cagcagggta ggcttgtttt gatttctctc 116580 tctgtagctt tagcattttg agaaagcaac ttacctttct ggctagtgtc tgtatcctag 116640 cagggagatg aggattgctg ttctccatgg gggtatgtgt gtgtctcctt tttctttcag 116700 gacttgtagg attctttgtg ccatttgcat ataatttggc aggttcacat tttttaagag 116760 ccctatgaag tgctttttgc atgtgtttta aaaaggcatt tgaaaattga aagtgtgatt 116820 tatggaaatt aaatcatctg taaaaaattg ctttggaaag taatgattgc tggccataaa 116880 gggaaatatc tgcgatgcac ctaatgtgtt tttaaccctt tatttgctga caatctatag 116940 tcattaatgc taaactcgat tttggcttca gctacatttg catattgtcc aacaatggtc 117000 tatttttgta agaattagat aaaatgtata cttgatataa aatagtcaaa aatgtaactc 117060 ttagtaacag taagcttggc atttagatag accatgaaca cttcgtcaga tactctgttg 117120 ggtgtttggg atagcaatta aaacaaagta ttgatagttg tatcagagtc tattaggctg 117180 cagcaaagga agtttattca aaagtataaa ctatccaaga ttatagacgc atgatatact 117240 tcacctattt tttgtctcct taatatgtat atatatatat atatatatat atatacacat 117300 atatgtgtgt gtgtatgtgc gtgtgcatgt ttaactttta attcagttaa aaactttttt 117360 ctatttgttt ttcatctgga tatttgattc tgcatatcct agcccaagtg aaccgagaag 117420 atcgagttgt aggactaaag gatagacatg cagaaatgca ttttaaaaat ctgttagctg 117480 gaccagaccg acaatgtaac ataattgcca aagctttggt tcgtgacctg aggttatgtt 117540 tggtatgaaa aggtcacatt ttatattcag ttttctgaag ttttggttgc ataaccaacc 117600 tgtggaaggc atgaacaccc atgtgcgccc taaccaaagg tttttctgaa tcatccttca 117660 catgagaatt cctaatggga ccaagtacag tactgtggtc caacataaac acacaagtca 117720 ggctgagaga atctcagaag gttgtggaag ggtctatcta ctttgggagc attttgcaga 117780 ggaagaaact gaggtcctgg caggttgcat tctcctgatg gcaaaatgca gctcttccta 117840 tatgtatacc ctgaatctcc gcccccttcc cctcagatgc cccctgtcag ttcccccagc 117900 tgctaaatat agctgtctgt ggctggctgc gtatgcaacc gcacacccca ttctatctgc 117960 cctatctcgg ttacagtgta gtcctcccca gggtcatcct atgtacacac tacgtatttc 118020 tagccaacga ggagggggaa tcaaacagaa agagagacaa acagagatat atcggagtct 118080 ggcacggggc acataaggca gcacattaga gaaagccggc ccctggatcc gtctttcgcg 118140 tttattttaa gcccagtctt ccctgggcca cctttagcag atcctcgtgc gcccccgccc 118200 cctggccgtg aaactcagcc tctatccagc agcgacgaca agtaaagtaa agttcaggga 118260 agctgctctt tgggatcgct ccaaatcgag ttgtgcctgg agtgatgttt aagccaatgt 118320 cagggcaagg caacagtccc tggccgtcct ccagcacctt tgtaatgcat atgagctcgg 118380 gagaccagta cttaaagttg gaggcccggg agcccaggag ctggcggagg gcgttcgtcc 118440 tgggactgca cttgctcccg tcgggtcgcc cggcttcacc ggacccgcag gctcccgggg 118500 cagggccggg gccagagctc gcgtgtcggc gggacatgcg ctgcgtcgcc tctaacctcg 118560 ggctgtgctc tttttccagg tggcccgccg gtttctgagc cttctgccct gcggggacac 118620 ggtctgcacc ctgcccgcgg ccacggacca tgaccatgac cctccacacc aaagcatctg 118680 ggatggccct actgcatcag atccaaggga acgagctgga gcccctgaac cgtccgcagc 118740 tcaagatccc cctggagcgg cccctgggcg aggtgtacct ggacagcagc aagcccgccg 118800 tgtacaacta ccccgagggc gccgcctacg agttcaacgc cgcggccgcc gccaacgcgc 118860 aggtctacgg tcagaccggc ctcccctacg gccccgggtc tgaggctgcg gcgttcggct 118920 ccaacggcct ggggggtttc cccccactca acagcgtgtc tccgagcccg ctgatgctac 118980 tgcacccgcc gccgcagctg tcgcctttcc tgcagcccca cggccagcag gtgccctact 119040 acctggagaa cgagcccagc ggctacacgg tgcgcgaggc cggcccgccg gcattctaca 119100 ggtacccgcg cccgcgccgc ccgtcggggt ggccgccgcg cccggcagga gggagggagg 119160 gagggaggga gaagggagag cctagggagc tgcgggagcc gcgggacgcg cgacccgagg 119220 gtgcgcgcag ggagcccggg gcgcgcggcc cagcccgggg gttctgcgtg cagcccgcgc 119280 tgcgttcaga gtcaagttct ctcgccgggc agctgaaaaa aacgtactct ccacccactt 119340 accgtccgtg cgagaggcag acccgaaagc ccgggcttcc taacaaaaca cacgttggaa 119400 aaccagacaa agcagcagtt atttgtgggg gaaaacacct ccaggcaaat aaacacgggg 119460 cgctttgagt cacttgggaa ggtctcgctc ttggcattta aagttggggg tgtttggagt 119520 tagcagagct cagcagagtt ttatttatcc ttttaatgtt tttgtttaat gtgctcccca 119580 aatttccttt catctagact atttgattgg aaatatgtca gctatgatga tgactttctg 119640 ggaagcgatt cctgtcaccc gctttcccct cctccccacc ccacgtcctg gggctttaga 119700 gagcgattgg gagttgaatg ggtctgattt cggagttagc tggctgagtc cgcgctggag 119760 cggattgctg gcatgtgact tctgacagcc ggaaatttgt aggtgtcccg cgagtttaaa 119820 acaagccata tggaagcaca agtgcttaaa aataatctcc tgccagccca gtgacaagcc 119880 tgtcccaccc ggggagaatg ccccggagtg gcgtgcgggt cagccagggt ctgcgcctcg 119940 cagccactgt ggaaggagcg cggccggtcc aggacacagg agaccacttt gtgacttcaa 120000 tggcgaaggt tgtgtgtcct cattttaatt tttttcccta caagaattgt tctttctccc 120060 tctcctctcc ctcccatttt ctcttgccca gtttctcctt ttgttttttg ttttttgttt 120120 tcctgatggg cctgcagagg gattaggtgg gcgcttctgg tgaacacctt cctaggtggc 120180 cacaggacag gtgtaccccg gactgggttt ggaagcttca gggcgccaca tggctgggtc 120240 ctgaattagg catttcccaa ctgtacactg gtatccggac tggtgtccct atatctttct 120300 gccttgtaag ccgtggacca gtttttgttc agtattctgt ttccagggat atttatagca 120360 gaaggaaggg gactaaagtg cagtttggcc ccagaggata ctgaagggca gattctgggg 120420 gtattcagtg tgcatcttca gccgccttgg agaaatttag agcatcccac agccacgcag 120480 atccaagctg tctttactca aaagacaaac aatgaacaaa acttttaaag gttggcatat 120540 ttcaaattaa ttttacttgt tttaatttag ggttaaaaca gagaaaaagg atttcttctg 120600 cccacctttt tttttttaaa tggaagaaca aagtacagcg attaagtcta attccacaca 120660 acatttaaaa ctgcttgatg tgaaggaagg cactggtatg atgtgaattc cataacctta 120720 tgatggactc cagaaaccat tttcttccct atttaatttt cagttctttt attgcaaatt 120780 aatgctgctg aatttcaatg ggcactaatg agactgctcc ttggtagatt atttactgcc 120840 ttgctaataa ttacaaagtg aacctggtca aatacagagg ggatcgcatc ttattcaaaa 120900 ttgttcatca tcccagtgat aagtggtatc agtgtaatat gccctatctt acactttctg 120960 cattacatga tattcaaaca ctcttagaat aataaaaaaa gagacaagga acttaaaaat 121020 taaaaaaaaa acttgcacaa atgggactct gtgtggaaat tcagttttag aatgattttt 121080 cctgtgtttt atttcccgga ttatctttcc tcttttgtta gaattctgcc tgttattatc 121140 cagcaaggaa aagaagcatc tatgcaagtt cttcatatgg acagatatta tttagtattt 121200 ttcccctctc agtttttctg cttaaatgac tctgggtata aaggaaagga ttgattgggc 121260 tcttttagga aactttaagt ttcttaagta gttctcaaaa gttttggggc tgaaagcagt 121320 gttttcaaac tgcttgtcat gacccagagg gtcatgaact cagtttagtg agtctagaat 121380 attttttaaa aggactaaaa tggaaaggaa tataatagaa aatatcagag tgcatggtat 121440 ttcgtaagga taagttttgt ttcctgaaaa tctgttttaa ttatatgtgc ttctgtgtgc 121500 tgattgtgat gtaaaatgta tttcttactg tggattgaat tcaaagaaaa aattagaaag 121560 ctaatggcct aaaatattat atgttcagta gaaaacaaaa aattcaggca agtggctggt 121620 tgtttttacc tatacaaatc aaaaggctat tttgattgtc ttcattttcc ccttataaat 121680 taggttggtg tctttagtca tttaggctaa gttttactat ctgattctta acttttctat 121740 tgtagaatgg tgctgtcatg tggactgtcc tcccgagtgt cccactggat gttcagagaa 121800 tttatgtgaa ggtcacgtca tttagcattg agatgctgtg gttaccttct tccatttctt 121860 ccataatatg cagccacatc tatgtgtgaa gaaatgtaat agataaaatt tctctggacg 121920 cataataatg tgagaaagat tgtcacatgt cccagcaaat tgttattaat ataaatttgt 121980 tacttggcaa gctgagattt tgcaagatgt tactcaaaat ttcacaatga aggaaacagg 122040 gagtcatctt atcctgggtt ccttttttag atttcaaaca acttaggaac tttgaataaa 122100 actaaagatg aagcttaact atatcaacta tcctttttaa agttctaatt aggaatttaa 122160 tgctgcatgc ttatttcagt tttattactc agtattctta aaagttagac gtctctcact 122220 tctccaaaaa acttggcaaa tgtataaatc ttttgcatca aaatcaatgc cctgctaatt 122280 tgtatcctgg ccatctgcat attttggaca actaattttt ccactggtga tcatttgaaa 122340 ctctttctca actttgaata gagactgatt tccaaagtga gatttaagtg actaagtttc 122400 aagtttccga tacatttttc cttttactta gataacattt cagccccctt cctttctgat 122460 cttacttttt tattaattta aattgttact gattacgtga cactttgtgc tggtctaaga 122520 atagtccaga gtcacatatt ccctggtgaa tgagcatatt ttcggatgaa aacggaatca 122580 catcttcaat ccccatttca ttttcacctc ctccatgtgg cttgtacctg tttggaagaa 122640 agctcctgaa ggataattgc cacttattct aatctttctc acactcattt aatttggatc 122700 cctggctaaa gttgttattt acttttgtga ttatacttag tctatgacat tcataatttg 122760 ggaaaattct caggtttgag aattttggcg gcttgggatt tcttttagtt tcttatagtt 122820 ttaaggatat gtaagacagg tgtaagaaac tgccaagggg aggaaccata gatatcagga 122880 aaaactagaa aagatgccag acttaccatt aatgaatgat gagacaatag taactttgtt 122940 aagtgagatt gtatatgtga aagtggtata gaaactaaac aaacattagg tgtttttatt 123000 attttactca catgttaata tttgttttgg tgctttcata ggctaaaaag ctgggaaata 123060 acagatttaa gtggtcagga attttgttat aaatatagaa tgatgattat atgaaatctt 123120 ttcctgtgaa agtcaaattt aagtaaaatc tttatcacca tctgcaacat ttgtctgcag 123180 cctggcttac caggttatca taaagaacat ttattttaca gatacattaa agaaagtcaa 123240 aaccctgatt atgtgtaaac aattttacat aaggaaatat atgaatttta attatatttt 123300 tctaaaatcc gtactcagca tgaaattaat acatcttaac ccctccctgt gacttcatta 123360 ttatttttaa tgtaacttta gaagaaccca gtagagagag cagcgtgcta agtgtgtttc 123420 tttcttttcc agacaacttt gaatggagag gagcaaatta gtcttttggt ttaattctgt 123480 ctcagtttgc ttatctaaag aaaggaaaac agagtggcta cacttgttta gaaccatatg 123540 catactccag agaaagatgc tctattaatc caaaaaatac agccacttga aaccagccaa 123600 agcgaaagtg taagggactt catggaaagg aggcagttca ccaaagttat tgaggggttt 123660 tatattttaa actccgccag tgaattgacg tgtaatgtca cttacaaaaa aaaaaaaagt 123720 atgtctgagc tgttcgctac ttcgtctcta aaatatactc atactgatct ctgaaatccc 123780 agaatttaag tgggctggag gttacgggaa gcacctttat aatatcctta atctcatgag 123840 ggaagaaacc ataattgctg aattctctgc cttggataat atcaggaggg actctgaaga 123900 aagttttgca gtaatcaaca atgttttaaa ttatgtgtat atttttagat cacctcaaaa 123960 aatataggaa gcacagaatg acaactattc tggtctcaac tgacacaatt ttatgtagtt 124020 taataaagta ataatttcaa gaaacgtggg caaataagaa agagtatgac tttcttacaa 124080 cccgcttgta agtgatgtgg tggtggtaat gatccatgat tttgatgatg acgatgatga 124140 tgaaaatgaa gtttttgtct cagtttgggt aggtggtatt tctggatgcc tcctatggac 124200 cctggagatg ttcatcctat acagaaatcc aatcctttaa atctacttgg ctcattgttt 124260 tagaattcta attccatagt ctgaaaattt taataatgat attaccaata atattagaaa 124320 cttattaagt acctataatt gctatacaaa aaatttaaaa gaacccaaaa ttccaagcaa 124380 gactgaaaat tttttgtctc tcctctgaac tatttagagg gacaaattag tttgttctta 124440 taatatctac tttaaataaa tgtgccatct ttaataagat agtagacttc tttgtttggt 124500 aatgttctat tttttggaga tcctatgagt tacacttggg aaaattataa aagttcactt 124560 aaagttaata aaatccatta agtaatgttc agaactagac atttccaaat gagcccttga 124620 aaagctcagg tgggttcttt ttgagagttc cccaaatgtt gtcaacccca ggaggaatgg 124680 aagacctctg cagttttgtt attcagattc tcatctcctt ctcagaagcc gtagaactgg 124740 ccgggcccta aggtccacgc tccttggttc cagttctgtc ttccatcctt cggtcccggg 124800 ctcattctgc ctgttcctaa acggtggcaa gttaggggcc ccagcagcca acttgtgctt 124860 acctggcact acttcctggg cagttttctt ggctccttga cttgttgggc ggcttgggat 124920 ttcttttatg gccctgaaag caaaagacaa tgttctcttt tagtttcctg caattaaatg 124980 atgttagaaa tagtcatctt cacattggcg tacttcctct ttcttctgta ggtcttttag 125040 aattttgagt ccattctcat attttcttgt ttcatttgct ttattttcta atacatagaa 125100 gtttaaactc cctttaaaga gtttttggcc tcttttaccc tattaagctt tcttttttct 125160 tttctgtttt agttgttcca tctgtgtatt ctcagatatt tttctttcac cttttctggt 125220 ttatttcttt attgacctgt ctcatctgtt attttaatga aatttggaac agggctaaac 125280 agagttccta cctcagccag tataagaata taccgtaata actcagagtg gtattaacta 125340 gattaaaagt ttcaaaaagt gatgtttttc ttgtctctga ggatagaaac ttcaacaaaa 125400 taaagaagaa attttcaatt agtagaattt ctttgaaagt ttgttcattc attcatttgg 125460 ctaccttatt ccaaattgag tcattcattg agggcttaga ctatataaag tgtggttttg 125520 ttttcccagc agttcatgca acagcattgc acctagcagc tgggaagtct tatagcatga 125580 ataggtgaga ttctaatacc agaatctcct gcatgtgtaa actaacagtg tagtcttgac 125640 tgttgtctcc cagtaaactt ggtttcagga gttttagatc catgtgaacg tgtacaaggc 125700 atttttgcta actgtaactt cccacttaat caacaaaaac aaaaacactc atttctgaac 125760 attcagtgca ttcatgatta atcttaatta caccacaaag gtatttttca atggtgattt 125820 tgcgggagtg gggtaacagt ttcgaaagca acattgtcag aaacatagtt gattttaaag 125880 gttctttctg gtgactttga cttctgcttt tttagaagac cttacacaga gttgtattta 125940 tttctcctgg aatatttcaa gcaattcaga gtgaaagggt atacattcca atttgcgtat 126000 gagataaaat ttagttacat tgagaagcta ttttctttag ttacagggaa aaaattgtag 126060 ggcttttgga agcctctttg atttctaata ggaggaatcc ctgagcactg gtccaaacag 126120 aaatcatctc ttcttcattg ctgtatttcc ctcaagctct tagcaaagtg catggcacgt 126180 gaaagcccgg agaagctgtt ggttgaaaga atggatggtg gtgggcagga agcatcaggg 126240 acatggtttg cttcagtcta ttggctggga gaaaggccat ttaggaaggg atccttagat 126300 gccactggaa gaatgtggga agtttgtgaa tctctctttc tcaggaacaa aagtagaaaa 126360 aggactccac acagcattcc aagtacagtc ggccctcatt attcatggat tctgtatttg 126420 caaattcgct gacttactga cgtttatttg taaccttcga gtcaacactc acggtgcttt 126480 ctcagtcctt tgcagacgtg tggaatggca aaaaaatttg agttatatga cgtatatgtt 126540 cccagctgag gctgagcaag gctcacttct ccttgcagcc ctcagactat aaacaagtgt 126600 ccctcttgct atctacttcg tgttatgatt tttgcatttt cataatccct gttgatgatt 126660 ttgctgttta aaatggcccc taagcatggt cctgaagtac tgtctaggga ttctaagaca 126720 aggctctgac gtgtcttaag agaaaatacg tgtttgataa gctttattca ggcatgagtt 126780 acaatgctgt tggccatgag ttcaatgatg gtgaatcaac aggatatatt aaatacagtg 126840 tttttgaaca gaaaaacata taaaacaagg ttatgtatta atgagttggc aaaaatgctg 126900 tgaccaaagg ctcccaggaa cctaccctat tttcccctca atgcaatggt tcagtatttg 126960 ctaattcagt gtttgaggtg actttataga acatgagtac catgaataat gagaatcgat 127020 tctgtataat agagtgatga aagcacaggt ctgggagcca gcagctatat ttctattctg 127080 gcgtgactcc tgtgtagttg tcatcactgg caaattgctt aactgtgtgc ctcagtttcc 127140 taatctgtaa aagctacatc gtttggatga tgtgaggatt aaacaaattc atagatgtct 127200 agggcttata acattcctgg cacataacaa gtcattattt tttattacta cttcggaagg 127260 gaattgagta ctataccctg aagaaggtga gtatgggaat tctctacggg tctggaatgt 127320 ccctatattt gtttattttg ccttcaagtg actaacttta ataccctatt gtgattagaa 127380 gttaaacttc tgcaaccaaa aggaagcagg aagctagtat ttcttgaagt gcttattaca 127440 tgccaggtac tgtgctacaa aaacaaaaca aaacaactgt aaaaaaaact tcaaatttgg 127500 ctgcgtgcag ctgctcatgc ctgtcatccc agcactttga ggaactgaag ggaggattgc 127560 ttgagtccag gagttccaga ccagcctggg caacacagtg agaccctgtc tctacaaaaa 127620 aacaaaaaca aaaacaaagg cactccaaat cagtaaaaat taatcaatca ataaaaagag 127680 tgaggggcat taagtattgt ggactgaagc aatcccagag agggaattaa ttgaagctga 127740 ggtaagcagc ttatggagaa gctatgatgt acagagggca aggaaggaat ttttctgtaa 127800 tttggaaaaa tgggaactgt gagaaagaag gagttggaag ctcatactta gggagcatct 127860 acaaggacgt ctttttcacg ttggttggaa tatccaaatc aaggattatt tcagaatcac 127920 ccagatgatt aaaaaactac tgagatccag gttgtatttc agcagttctg acaattgctc 127980 tgggtcgaag cttgaatcag tagttaagaa aaacaacaaa caaaacaaat tttggggctt 128040 ttctcactga tttacagtta aagctcattt actcttccta tgactttaga tggaggatat 128100 ttccaagtct tcaggatgga gacatggagg gaagtgagac tagtgatgtg cctcaaggtt 128160 ttgctgttgt tctaaccatg aggagcacta ttcaaaccca ggtctgctag atttccaagt 128220 cttcatttcc ttgggcctct tggatttcag aagcagaggg taaaaggagt gctggggaga 128280 aagatcacag tagctttcaa ttctactcct cagctttcca aaataagttt caagactggc 128340 cgttgcattt gatatggaat aaatacaaag aaggtagatt gaagggtatg aagatgcaga 128400 tttttgatac cagatatgaa gataacatta ggaagcaatc taaaacatgg acacaaacac 128460 acacctgtgc cagttagcct gtataattcg atttttgtta agtgtttaga taactgaagg 128520 taatttaagc cctcatatct tcccttcata gggttctttt tccctctggt tcatcagaga 128580 gttgccacca attcaggctg ttagtggtac acataacctc tagcattgtt gatacagcta 128640 taaaatccca aatatcagta caattgttga ttgcataaaa tttccagttg catggttgga 128700 aagtcctgta agtttgaatc cttaaaccag tcttaaatgt ggaggaggac tcaattaaag 128760 ctctcctcgt gtcctccctc tgacgtattt gcaaaatcct ttccacaaat agaatactgt 128820 ttttaatgct tccccagtcc aattttgcgt tgtagaagac gaatttatgg atgagggaag 128880 tggcattcag gcactccagc ttggtataga agcccatggt gtctggtcct cagtcctcaa 128940 gcccgctcat ttcctcatgt gaactcagaa taagcagctg aaagcaagtc ttcaaaatct 129000 cagagatatg tataaatgca agtgtttggg tgagaagtga acatgggtct cctctagtgc 129060 ccacactact tgactaacag gttttgggct ccacacaatg agggattatc aacccctgtc 129120 ccagggctct ctgggtcttg gttctttgtt tttgatgctc agcaattgtg atcagtgaaa 129180 ccaatgttgc ttttctatca agagtccaac ccttttctaa gaagggttgt gtttgatatt 129240 agggaatagc tagcaaagtt atcaagtaac ttgtagaaac attcttttgc aagagttctt 129300 atactgaatg actgtagttg acagcagtgc agtactggtc attttctagg acatcttaaa 129360 aacactgatg agaagtttcc tctcagatgt ctgtcatgtc attcttgcct ttctctacac 129420 agggtcagtt ttctcttatt gctgttagga gttcctcatt ggtttttcag cttttgggct 129480 ttcaaactct aattaatcat aagctactag agtgtactac ctaaagtgtg tatatacaca 129540 tatatacaca cacacacaca catatatata cctggtatac atatatatat ataatataca 129600 tatatcatat atactcccca acctgatctg gttcttcctc tgcataaaag acctcaggcc 129660 agtcagagaa aacatgtatg ttccatggtg tggcaatcaa gcccttgtat ttggttccaa 129720 tcagtctcct aactattact ccaagaagct cttgttgaaa gagccatgtt taaatggcat 129780 gttcctactt tcttcttcat agtgatcttc atctgtacca tgtacccttc tttcttcttg 129840 ttccatctct gttaggctga ttctacccag aagtcaaggt tcagctcaaa tgctatccct 129900 atcaggtgaa ttttccacct ggcatttgtt cggtgtgcat tgtgtgcata cagcaccttt 129960 tcccggtacc tttactgtaa tcaccagata attcctttca ttttagttgt aaatagagtt 130020 gtcttccccc tctatggaat agattttatt aatgtataga gcagcagtcc ccagcctctg 130080 gaccatggac tcgtactggt ttggggcctg ttaggaactg ggccgcacag caggaggtga 130140 gcagtgggca tgcaagtgat gcttcatctg tatttacagc tgctccccat cgcttgcatt 130200 atgcctgagc tccgcctcct gtcagatcag cggtagcatt agattttcat aggaatgcaa 130260 accctactgt gaactgtgta tgtgagggat ctgggttctt cttatgagaa tctaattcct 130320 gatgatctgt cattgtgtcc catcaccccc agatgggact gtctagttgc aggaaaacaa 130380 gttcagggct ctcactgaat ctacattatg gtgagttgca taattatttc attatatgtt 130440 acagtataat actaatagaa ataaagtgcg caataaatgt gatgcactgg aatcatccca 130500 aaaccatccc cagttccatc tgtggaaaaa ttgtcttcca tgaaaccggt catggaactg 130560 gtgccaaaaa tgttggggac cactcttata aggcatatta gagtaatttc atagatttcc 130620 taattcattt atcatattca ttcactcagc aagcattact ggatgttgat catgtactgg 130680 ctttggtggt aggtgcagag attgggaaca ttgtcatcaa ggagtttatg gttgagtgag 130740 ggagatgaca agtggataga caatgaaaaa acagtagaat aagaactgtg atagaaaaga 130800 gacagccagg agcattgagg agaggcactt aaccagatgg aggatcttgg tccattgata 130860 tggaggtcaa aatggtttaa tagagcaagt gaccctttca actgaatttt ttaagaatga 130920 ggatttagcc agacaaagaa gggcaggtga ggttgtgaag aggaactgag tggtactctt 130980 cagagctcca gcccagttcc ttggacagaa taaatgctta ctaacttata gagctgaata 131040 ttgaattaat aaaataaggg taaactgtta agaatcagag aaataactta aagaacactg 131100 atagctagtg ttttttgaac accatgtacc caggtgcctt gccgaaaacc ttaatgatca 131160 tcttgtttaa accttacatt tctcataaga ggctggtact attgttattc tcattttatg 131220 ggacgtagaa actaagactt ggagagggga agtgacttgc ccaaggtcat acaaccagta 131280 ctggagaatt agggattcta gatctagaat ttggactctg gagcttaagg ttttaaccca 131340 cgacattatg cagagaaatt gacaggattt ttctgttgct gatcaattta cttggcagtt 131400 agtttgttac ttccttgtct ttattttagt tgtgacaatg ctttcatctt agactgtgtc 131460 ccgaggctgc tgcttttatt tttatgggaa atggctattt ttatgatcct tgctaaaagc 131520 atgtttaaac aattttccat taagtagggg gatgtttttc cttctaatat cagaagccaa 131580 taaatgaaat tctacaaaga cttgctggta gcaaccttag gaatttcttt gcatgtgaaa 131640 cccatctgag aacttaaaat ctgggtaaaa ttgtagtgta atttggtgca atcgtctctt 131700 tgcacaaata acatcataaa atcatagtat tgtcatctag gaggggcctt agacatgatg 131760 gaatcctacc ttttatattt tccaggtgaa gaaatcaaag tctagaaagg tgaaggaact 131820 tcccccaaag tttcccagct ggtagagaca gaaccagggc taggtcctct attctgactc 131880 ctgaccacta cctcacacct aatagatgga ggcatgccca gttcctgttc accgagggca 131940 tcagaccatg ccatactcat tgctactgtt ccagcattta tagtagaagc tcaagcaagc 132000 aggatgacag aatacctaat tctggtcact acaacattat aatgatggct aaagtgaatg 132060 ccccagccat gcttgtctag acaggccatc tgtttaattg gtatatggtt cacgtgagaa 132120 tttttaacct ctgtttgtcg agtcggtgtt agttctctag tgatgaatta tttcctatac 132180 ttccatttag attatttact cttaatttaa taaccataca ttgtttactt tggtattgaa 132240 gattcccttg tttttcttct ttttttctgt ttccagggct taaaggttag gagtgacctt 132300 gccagacttc cctggagact tacactgtct cctttcagat ttctgaagca gttgggtgct 132360 atttttagtc cactatcacc aatgtgaaaa tggaacttgc attatttcat tatagatatt 132420 tcactttagt attgacagaa ttaaaaaaat aatttgatct gtgcttgatc tagcagccag 132480 gttacaatag acatttttag ttacctggtc cacatgttga aaaacatgtg tcttctctga 132540 gactaatgac taagcccgat gttggttata tactgtttac tattaaattt tccccttgta 132600 gtttaatatt gttccaggaa atgaaatgaa agtttaataa gaatggcaat tgatggaccc 132660 atatgtcgga agtataacta atgtccccgt tacatgtgtt aaagaaaggc atggctggtg 132720 ggttgtaact gtactacacc aagatgattt gacacaactt attctacaga gatatatatt 132780 tatcaggata gaatttataa ctaaacaaaa ctatagcatt ttttcacttt gatttttttt 132840 aaatgagtca aagaactgct agaattgtca gttaaaaaat tttaaaagga gatatgaaaa 132900 aatcttacaa ttcacaatgc tgtaaagaga taatgtaggg attaatatgt tcttgatatc 132960 aatattttat gacttttata catgtagaag caaaacaatt tgaggtaggt gaagttagta 133020 tggacttctt gagattgtcc ttcacatttc ttttcctttc ggtgaaaaat tgaaggccaa 133080 aatgtatttt cttctggttt tgaaaatact gtcaagatcc ttgcaacaaa atgagttcct 133140 ctaaggagct gaaaacaaag ctcactcccc tcgtgatact ctgagaggct ttgctcagca 133200 tcctgcattc tggtgattcc ttggagacag atgatgctaa acacaggaag attaggtcaa 133260 tggtaacttt ttctaagtca atatttcttc tccttgggag atgatcattt taaatcttcc 133320 cgaagtccag gctaaacctt tctaattgaa tctccatgaa ggagagctcc agcaggtgga 133380 gaggaagtga gaaagagaaa tgaaagctgc acgcctcatg acgctgtgcc agggagttct 133440 taaaggtgag ggagtttctt tttggtaacc taagctatgt gaatcagaag gttcattagc 133500 ttgtttcttt ttcttttttg taaactccta cataatttta gtaaacagga acagtaacct 133560 aatgtgatat cccactggcc caagacttag tgcatcttca aagttgctta attatgtccg 133620 aaacagactt ttgtctcttg atgagaaaag catggttaaa cgtgtgatga tttcctattg 133680 tcctgagctc agatctgtaa ttgtggccag attcatgcat ctctgctgcc ttctcttaga 133740 agaatcatat gtaggcttgt cagataaaac aggatgccca ggtaaactgg aatttcagtt 133800 aaataacaaa taacatttta gcatgtccca tgcaatatta tactaaaata ttatttgttg 133860 tttatctgaa attcaaattt aattgaatgt cctgtatttt tgttggttac atctggcagc 133920 cctagccatg ctgcctttct gcttaatggg cttaattttt tgaaggctgg aggttttctg 133980 ttatggtgcc cgtttccacc tgcttttcta ccaggaaagg aggcatgctg atgtagaatt 134040 tgcatcctta tttttgtcat tattattgat tataacagat gacataggtt tagattaaac 134100 ctacaatgac attgctgtca ttcagataat tgtaattatt gctaattgta aagaaggata 134160 attttttttg aaatgactat tatttgtttt ttgtttttgt ttttgttttt ctttttttct 134220 aattatactt taaattctag ggtacatgtg cacaatgtgc aggtttgtta catatgtata 134280 catgtgccat gttggtgtgc tgcacctatt aactcatcct ttacattagg tatatctcct 134340 aatgctatcc ctccccccta cccccacccc acgacaggtc ccggagtgtg atgttcccca 134400 ccctgtgtcc aactgttctc attgttcaat tcccacctat gagtgagaac atgcggtgtt 134460 tggttttttg tccttgggat agtttgctga gaatgatggt ttccagcttc atccatgtcc 134520 ctacaaagaa catgaactca tcctttttta tggctgcata gtattccatg gtgtatatgt 134580 gccacatttt cttaatccag tctatcattg atggatgttt gggttggttc caagtctttg 134640 ttattgtgta tagtgccaca ataaacatac atgtgcatgt gtctttatag cagcatgatt 134700 tataatcctt tgggtatata cccagtaatg ggatggctgg gtcaaatggt atttctagtt 134760 ctagatccct gaggaatcgc cacactgact tccacaatgg ttgaactagt ttacagtccc 134820 accaacagtg taaaagtgtt cctgtttctc cacatcctct ccagcacctg ttgtttcctg 134880 actttttaat gattgccatt ctaactggtg tgagatgata tctcattgtg gttttgattt 134940 gcatttctct gatggccagt gatgatgagc attttttcat gtgtctgttg gctgcataaa 135000 tgtcttcttt tcagaagtgt ctgttcatat ccttcgccca cttgttgatg gggttgttgt 135060 tttttttctt gtaaatttgt ttgagttctt tgtagattct ggatattagc cctttatcag 135120 atgagtagat tgcaaaaatt ttctcccatt ttgtaggttg cctgttcact ctgacggtag 135180 tttcttttgc tgtgcagaag ctctttcgtt taattagatc ccatttgtca attttggctt 135240 ttgttgccat tgcttttggt gctttggaca tgaagtcctt gcccatacct atgtcctgaa 135300 tggtattgcc tgggttttct tctagggttt ttatggtttt aggtctaaca tttaagaaga 135360 aggatactta aagtataagg gaaaatgtta caatgtatga agggaacatg aagaaataga 135420 atctggtaaa aaagagttct tgcttttggg aggccaaggc ctcctggcta acatgatgaa 135480 acctcatctc tactaaaaat acaaaaaatt agccgggcgt ggtggcacac gcctgcagtc 135540 ccagctgctt gggaggctga ggcaggagaa ccacttgaac ccaggaggtg taggttgcag 135600 tgagccaagc ttgcaccact gcactccagg ctgggcaaca gagcgagact ccatctcaaa 135660 aaaaaaaaga aaaaaaagag ttcttgcttt caaaactatg gattaggtaa cttttgtgaa 135720 tgagtaagat catgagtatt ataaaaatag cacctttctt ttttgtcttg gggaaattat 135780 cttatttttt aattggattt cagaaaagag tatttcagag aaataaatct ctgaaatgct 135840 ttttgaagtg tgaaagattt agaagacaaa agcaaacctc ctgtctagat aaacattaaa 135900 gagatctgcc ctcccctcct ctacctattc aggttgcaac actttggggg tggctgcctt 135960 ggtagagctt gatcgtgact ctggtggctt gggagatggc atgctgcaca agggattcat 136020 ggttacagcg ggcttgtggg actggggctc tccaatacgt ggttgggttt gtaaagaaat 136080 cagagctatg gtgtgaacaa aaggatatgc atgggagaca gtgagacaag gaaatgctcc 136140 agaaattatt ggaatatagg tcagataact aactgtactt gtgccatttt ctgggggaaa 136200 attctctgaa ggctttttgg gaaaagaatg gaagtgagaa ttctcaggtc ctcaaaatat 136260 ttccttttac tcagtcctaa cctgaggccg ttaaagaatt cccagagtca cgatggaagg 136320 catgtttggg agtaagagcc agagtgaggg ttagaaatgt gttgttggcc aggtatggtg 136380 gatcgcctgt aatcccagca ctttgggagg ccaaggcagg tggaccacct gaggtcagga 136440 gtttgagacc agcctggcca aaatggagaa acctcgtctc taccaaaaat acaaaaatta 136500 gccaagtgtg gtgacacgtg cctgtaatcg agctcttcgg gaggctgaga caggagaatc 136560 acttggaccc aggaggtgga ggttgcagtg agccaagatc atgccactgc actccagcct 136620 gggtggcaga gcaagactcc atctcaaaaa aaaaaaaaaa aaaaaagaaa gaaatgtgtt 136680 ttccagggtt ctgggtactt aggaatttgg ttgcttttgc aggtggaagt ggaggtgact 136740 aggtaacagc tgagtgattt tgccccagtt ggacatgagc caggttgagc agaaagccct 136800 gggatgcggg gaggggggtg gcggggaagg aattgaaagt tggttgtgtg gtttggcttt 136860 ggcttcatgg catgctcaca ccttgcttcg catagcatgc ttagactaca gcaggagcat 136920 caggaagtgg atttctgagc tcaatacaaa aagttataaa taccacctat aagggcaata 136980 aagatatata gttgattttc ttctttgcaa ggccaaatct tataggaaca taagagcgaa 137040 tgagttacag cctgggaatt tgagccttat attcagagat tttaggttgc ttctgattcc 137100 gctgtctaga caaaaccatg agaggatagt gtctagaaat gagaggaagc tcttccaatg 137160 cagaggctag aatgtgtcag cctgtgctgc gaggcctggg atagatgttt ctgaaaagta 137220 aaagggcagc tttcctactg gatacttgat cctcaggctc tagaaaactc tgctttatta 137280 actttgttga cttcctaggc accacatggg atccttgttc ttcctccttg taagcagtaa 137340 ttgaaatcag tttggcagcc tggtttacag tgaccatggt ggcttgtctc ccgtgctctt 137400 acctcactct gttgatgttg taaaacctcc agctaacttc atggggtggc tgacccacgt 137460 tgctcattta ttcattcaac acatattcat tgaccatcta ctctatgcca ggtattgtta 137520 tcagcactgg gaatagatca gtgaactatt gatctatttg tctaatggga caaattgaca 137580 aattgggaaa gattccatta cacaggtgac atttaagcaa agtcttgaat aagggaggga 137640 atagtaccat gagatatcct ggtgaaaagc aatttaggct gagggcacag cagggaagag 137700 gccctgatgt gggaacatcc ctggtgtctt gaggtacagn angcggcatg gctggcacgg 137760 agtaagaagt tggaggtgcc gggcatggtg actcacacct gtaatcccag cactttgggt 137820 ggctgaggca gatgggtcac ctgagcccag gagcttgaga ccagcctggg caacatggtg 137880 agaccccatc tctacaaaaa aatacaaaga aaattagcca gatgtggtag catgcatctg 137940 tagtcccaat tgcttgggag gctgagatgg gaggatcaaa ttacttggga ggctgagatg 138000 ggaggatcac ttgagtccag gaggtggagg ttgcagtgag ctgagatcat gtcagggtga 138060 cagagcgaga ccctgtctca aaaaaaaaaa aaaagaaaaa gaaaaaagaa aaaaaaagaa 138120 gnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 138180 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nacaatactc tgctcctctt 138240 actttttcct gaaatttgtc acattgacag caatgtgatc cctaatgaca cacagattcc 138300 caaataattt ttgtagtaaa aatttccatt tgcaattctg gacatgtgtg tgtgtggaat 138360 tttatgtgat gacatattgg tcctatcttt tgaataggat cataaatgaa atgacttatg 138420 gatcacattc aaaagcaggc cagggcaact gtgtaagcag gtgggttttc atatttggag 138480 ttctgtactt ttgtgttagt cagtgggtct aggactcttg tagtgtattt cccaagggcc 138540 aaagtcttct gccttgaggt gtcagctttc caaggcagag gctggatgct ttctcttcct 138600 tctgggctcc tttctcttag gcttccccct tctcttctcc tccatttgta tctgtccttt 138660 ttctcggtac tttccctggc tggtctcagc tagatgctca ctcaatgctg ttgaataaat 138720 gaatgaattt cgtagtaatt ctgcaggtaa atcaagttat tgtctcccaa tacggtgcta 138780 tgctttctga ggaaattaga ctggaagtca ggctttttaa aaaagaagat gtggtgtcaa 138840 attgcagctc tctctctctc tcgacttacc ttttttctat catccatatg ccttctttct 138900 tgtatctttg ggttcccaga cctcaccatt cattagcact tggaatggat tggtaagaat 138960 aaagaaagga gaggtggtga aactcagctt gggtcatctg gttacacatt agtaactgac 139020 aaaagataaa aagatacaga ctaaatgggt ttttagggaa ctttttccag tctattcttg 139080 tttcccatta gtgtgaaaaa tcaacacttg cttgtatttt ggggtgaaga catttttctt 139140 aagtgagtgg gaaagcctct tgacatttta ccgagagcct taaattttga atggtgaatg 139200 ctaatgttct ttgtgcataa agaatttcag aacttgtata tatgagcatt aatgatgcat 139260 cattttctat ttgtgagtta aactaggtat tatctgtaat catattttta ggaaacattc 139320 aaactttcat caagtcattc tcttatatga ctctcagctc cattaactct gttttcatgg 139380 aactcaacag agttcttaac gtttgcatta taaattaaat tagcatttcc cctcaaagaa 139440 gtattgctgt ccttacaata aataattgta gacaatttct tttcttttct tttttttttt 139500 tttgagacag gttctctctc tgtcacccat gctggagtgc agtggcacag tcacagctca 139560 ctgcagcctt gacctcctgg gctcaagcaa tcttcccacc tcaacctcct gagtagctag 139620 aattataggt gcacaccaga cctggctaat gtttaaattt tttgtagagt tggggtcttg 139680 ctatgttgcc caggctggtc tctaactctt gggctgaagc attcctccca ccgcagcctt 139740 ccagagcagt gagattacag gtgtgagcta ccatgcccag ctaattgcag gtgatttcta 139800 atgggattta gtatttctgg gtttaaggat gagatctgag gtaatgactt tgtttccaga 139860 tgtgaaataa tttgctcttg ggttgtgagc cctttgggtg ggctcccaag gatcctgctc 139920 tcttccagga gcccaggctc tggggtcaga ctgcctgggt ccttgactcc ctgttttctg 139980 attgtacaac tttggtgagt ggcctaattc ctctgtgcct tggctacctt ggttactatt 140040 tctaaaacaa ctggtgttgt agtagtactg cttagagtac tttcaagggt taaatgaatt 140100 aatccatgta aaacgcttaa aatagtgcct gccacaacca tcaatttagt gtgaaaatct 140160 gctcacctgc ttggccagcc cctttcactt tattaaacca agggtcgtgc tgggttttcc 140220 agaagtctaa gttgcggtct aatctttgtg cagaagctga aatagcagcc ataacgttct 140280 ccctagatga tttcgtggag cttctttgaa ctgtatctat ctccagtcat ttttgtggaa 140340 gaaattttct tctgtacttt ttagggatga gaattacctg ccttggttta ttaactaaaa 140400 gacaccatga ttacaaataa aattaaataa atattgtatc actaaataga taatatgaga 140460 tagatgtatt aagttttcag ataaacagta taaaagagct agagtaattt gtaaaaagtt 140520 gggaggacct attttgtcat gcaggaaaca atttttaact tgcctacccc agaacatagc 140580 taccacatgg ttagggtttg cccaaacctg gcccaggagt catttacctt gagctttcct 140640 aaaaaggagg atcaggattt tcctctccag actctatcat tttaggtaga gtccttcttg 140700 tcaattcttt ttaagaacat acatttactt ttgtggaaaa taaatagata caaaataaat 140760 acatacaaaa ttgcatagca attagaaata cccaggaggt atgttatggt cacagacaca 140820 aactgcctcc aacttctgtc catccatagt gatatttaaa gcagagagag gtacacaggt 140880 aaccacattt agatggactg ggatgttgcc acacatacaa gcattgataa ctggcttctc 140940 attacctgaa tacattcttc tgtcagagca acagactcag ctatgcttct ggcaaaattg 141000 ttcttaattc tctattgatt aatttattcg gtaagtattt attgggtatt ttctgtctga 141060 aaagtgcgat tccaggtgct ttatgtgtct ctgtgtgtgg gtgttatata aatacttata 141120 atactgtatc catactcttg aaaagcttag ttgggaaggc aaggcatgca ataaggaaca 141180 cagaatttta gtcattccac aaccatctgt tgaatggctg ctattgttag tatcgtggtg 141240 gaaactgaga agcaaagatg actataatag gatctctttt ctggagatgc acagtggaca 141300 cgtagttata tgatgatgat aaggactcca gaatagttct atacatgatg ctctggggcc 141360 acatgcagat tctgatgaga aacaattaac tctttttggc tgctacctga gaaggggtaa 141420 ttgtcactca ggaggttttt gccttttgac caacatagaa aggagtgtga gtgaaggcta 141480 gaggtgtact aacttggtca gggcagggtg acacataaaa ttaaccatca cagggaaggg 141540 tagggctgga gaggcagact gtggccaggt tacaatgcgc tgaggctaag gagactgtgt 141600 ttatcctgta ggccagtggg tcttactctg aagtcttttg ggtgggacat tcatggactt 141660 caagagacct gtgaatgccc taagattata agtaaaatct gtgagtctgt aactaaagct 141720 aaagctattt ttctggggcc caccatctaa agaagattct gaagccttag ggtagccgtg 141780 gaggagacat gaaggtccat tttgcatggt agaaccctgc ctggctcttg ctgcagtgtg 141840 ggaggacagg tttgcaatgt ggaggtgtgg caggcatgga tttgggagga ttggcagagg 141900 actcaccatg tccatacact cactgagatg gcaaatattt attaatcatc caactgtgta 141960 tcagacacta agaataagct gggaggccat ggcaagtgag gtcaccacag tccctgccac 142020 agtggaggtt atggtataca ggtaaggcag ggaagagcac tgcaaagggt ttgcccattg 142080 catcagtcat ttatttatgc acatgttgat tcaacaatta tttctatgcc aagctgtctt 142140 caaggtgctg gaggaaatga agcgtacatt tcactgggga agacagacaa taagtaaaca 142200 cattaaaatc tggcttggct tgatgttggg gaggggtgag tgccatagag aaaacaaacc 142260 atttatgcag ccaacaaaca tatgaaaaaa atctcatcat cactggccat tagagaaatg 142320 caaatcaaaa ccacaatgat ataccatctc acgccagtta gaatggtgat cattaaaaag 142380 tcaggaaaca acagatgctg gagaggatgt ggagaaatag gaacactttt acactgttgg 142440 tgggagtgta aattagttca gccattgtgg aagacagtgt gatgatccct caaggatcta 142500 gaaccagaaa taccatttgg cccagcaatc ccattactgg ctatatacct aaaggattat 142560 aaatcattct actagaaaga cacatgcaca cgtatgttta ttgcagcatt gttcacaata 142620 gcaaagactt ggaaccaacc caaatgccca tcaatgatag actggataaa gaaaatgtgg 142680 cacatataca ccatggaata ctatgcagac ataaaaaagg atgaagtaat gtcctttgca 142740 gggacatggg tgaagctgga aaccatcatt ctcagcaaac taacacagga acagaaaacc 142800 acacactgca tgttctcact ggtaagtgga aattgaacaa tgagaacaca tggacacagg 142860 gacgggaaca ttacacacct ggggtctatc agggggttgg gggctaaggg agtgatagca 142920 ttaggagaaa taccaaatgt agatgacggg ctgatgggtg cagcaaacca ccatggcacg 142980 tgtataccta tgtaacaaac ttgcacattc tgcacatgta tcccagaact taaagtataa 143040 ttaaaaaaaa aagaaaagaa aacaaaccag tgtaagagga tggaaagtaa taggctcgtt 143100 tagaatggtg tgagaaagcc aggcagggag aaggcgctga gacagggagg tcctggatgt 143160 gtttgtggaa gagctgtggc agcacctgga acttggggag caagggaagg agtgtgggca 143220 ggcaagggtg agggtgcagg gggtcatgct gggccttcca ggtcacggaa ggacttgagc 143280 tttactcttg ttgtggtgag aagctgctga gggcttggag ttaggggagt gaaaagatct 143340 ctactataat agggagagtt cgggatctgt aacttaaccc caggagccag caaagctccc 143400 tggaggaaat gcagtttaag ctgagaatgg gaggataaac aggtgttttt cagagaagag 143460 gaagggtgct ctaggcacag agaacaacat gctggaatgc ttctactaga tcataggggc 143520 aaaatgggag tgcaggagta ggagagggct ttctgggaaa gatacttatt ttaattttgc 143580 atgcattgag tttttgaggt ttctttggtt tgttcatgtg gaggtgcaga gtgggtattt 143640 agcacatagg tctgaagtcc aggggagggg tgtgggacag cagttggatg tggcagagat 143700 tccacaaaga gcaaatatca tctgagaatg gcagagggct gagggcagag cctgaggaac 143760 actggtgttt aggagcctgc tggagaaaga aaatactgca aagggaacgg aagtggagtg 143820 gttgccagac atagaagcta gtgtctaact agatgtcatg agatgtgggg aaggtgttac 143880 gtatctaaga atgcaaagtt gaacccctgt gaactgtaat acttaagata agtcgtataa 143940 attgtctgga actagagctt gattttccag gagagatgaa atgtgtgtag gtgacaggaa 144000 acaatgaata tgtgggcgag tgtagtgtga gcaatttctc agaggtgaat ttgacagcat 144060 tttgcttagg aagctacaaa gagaccaatg ctagttggtg caaggaattc aagaatttgg 144120 acttaagtct atataatgat gatttttttt ttttaacttg agtttcccgg tttatcactc 144180 ccagaatata ggcagaagtt tgagattttt atgtgtattt tctggaaaag atagtttcag 144240 tgttttttac attctcaaac aggtttatga tccaaagaaa aggcagtggt cacagataca 144300 tgaaacgaca aggtattcaa aggagaacgt tgtactttat gacagttctt tgggcagtgg 144360 cttgcaggat gagtttgagg aatgattgga ggcaggagag taattctagt aattcaaatg 144420 tggagtattg ttgatctctc agacacaaat ggaaaaacaa ggaattcaaa gaaagatagg 144480 cagagtgttt tgaagaaata attgatgaaa tttggtaatg agttagatgt aggagatata 144540 tttagcaaat atttattaag gactgtatta atctgttatc atgctgctaa taaagacata 144600 ccaagactgg gtaaattata aagaaaaaga gatttaatgg actcacagtg ccacgtggtt 144660 ggggaggcct cacaatcatg gcataaagca aaggaggaac aaagtcacgt cttacatggc 144720 aatagagtgt gtgcaaggga actgccattt ataaaaccat cagatttcat gagaaatatt 144780 cactatcatg agaacagcac agacaaaagc ctgccaccat gatttaatta cctcccactg 144840 agttccccca ggacacatgg aattatggaa gctacaattc aagataagat ttaggtgggg 144900 atacagccaa accatatcaa ggacctactg tatatggtta aaattgggag caaatgagac 144960 atgattcttg ccttcttgga gtttactgtt tactagggga acatacactt gtcaataatc 145020 acccaaatat aggattggaa attgtggtaa gtgccatgaa aaacaagtat agggaatttt 145080 gagtgtacat agctttgggg acttgatttg atgagggagc cttatgaagt tattgcacta 145140 gaactgaatt aaaccacatt tctaggaagt ggacatctat ttgttggttc tttaaattta 145200 gctttacaga aatatttcct ttaaaaacca aggcttctta aatttttaaa actgcttggc 145260 taatcagggg aataatgctt ttggatagct ggtatcgtta tttatggttg gaaaaacaac 145320 agtatttgat tacattgagc tttaaacttt tcctttgatt aatgaaaatt ttattggccc 145380 atagttttta ttatgctctg tttttacttg gtccaagaga ttctattctc tggacccaat 145440 atgaatacct tcagacatcc ctcttttttt tttttttttt cacccaggct ggagtgcact 145500 ggcaatntct aggctcactg caacctctgc ctcctgtgtt caagcaattc tctgcctcag 145560 cctcccgagt agctgggatt acaggcacct gccaccacac ctggcttatt tttgtatttt 145620 taccagagat ggggtttcac catctcggcc aggctggtct tgaactcctg acctcatgat 145680 tcacccacct tggtctccta aagtgctggg attacaggca tgagccacca cacccagccc 145740 agacatccct cttaattatg ttgaatatgt aatatcggtg atttcatttg aaaatattta 145800 gtagtcgaac tagatcaagg cagttaagct tcctatttcc atagatgcag tggtattgtg 145860 tcttttttat atgatctctc atgcttctgg acatcctttt ttctgctatt cttcattcct 145920 tagctacact tggtgcttcg tggttgtaat gcattgtcat agatgcgttc atttctcatt 145980 cgatcttcag ctctatttct ttccagagaa tctctacagg catctgttag gttgaaggac 146040 atctaatgtc ttaatgtgta gcttggtaaa ccagtcaact ttctatctga gtcttaagag 146100 aaagtgtcca agatgagaaa cggtacaggt ttggtgacaa ctcagtgaga aaaagaagaa 146160 ttttacaagg aaggaggtat cttagtaatt ttgctaaaga agtaggtaaa ccttcactta 146220 taataaaggg atagggctcg gttagggttt gtgaagtctc cccttaggaa agcaaaccct 146280 gaaatatttt gaatctttta aagaaggaaa ataagagtct tttaaataaa tttttaaaat 146340 ttattttata tattttttat agacaggctc tcactctgtc tcccaggctg gaatgcagtg 146400 gtgcaatcat agctcactgc agccttgaat gcctgggctc aagcggtcct tctgtcccag 146460 cctcctgagt agctgggact gcaggcatga gccaatgtgc ccagcaagag acattcattt 146520 tggtactgtg atggtacaga aaaacaaagg gcctttgagg ccgaaggagc agaagaagga 146580 tggacttaga catggtatag gcactttcta ctaaagagct gtgaagctaa aaatgccagg 146640 tctatgacag gtgcagtggg ccaaggccag gtagagagca gcaggaagag aggaggtggg 146700 gacctgtacc taggcccatc tgctgggact gatctagcca taggtactca gagaagccca 146760 gattggtgcc tgacccaccc ttatggccca gacatggaca cctcccagtc tgttccttcc 146820 tgctgcccat ggatgggctg tgttagtctg tattctgagg acacagctct ctgtctagag 146880 gaagttatgt tatcttgatc tgatggatac tcaacgtgaa cattatttca acgtgccaca 146940 gggtcttgga gcccagagga agaccgctct tgccttttag tttatattct ttgttttttt 147000 ttaaataaca ttttgacagt ctttatggag taagtctggg ccaaaatgat aattgacaat 147060 gttatttaca tggatttcta agttggctaa aaaagttcct ttatggttag tgaatatagc 147120 ccatgtagtt tccccgtctt ctttagatgc cttctatttc tatgcccaaa gtctgcagtt 147180 gattttcagt aagctggggg tcatcttaga gataaaatgt agatgaatgg cattttgctg 147240 acagcataca tctttgctat ttctgaggaa aatgggctct cgctattaaa tcttttgtca 147300 atatttataa aaatagtatt tacatattct atctatattg tggaaactat acatttattg 147360 attcagtcat ttgatatcaa tgttgttgag tccctattcc aagtgaggca ctatgctcta 147420 agcacatggc attttaaaga tgaataagac accaagaact ttgcagatag taatggaaat 147480 gagaattaat caattgaaga ttaatatagt aagtagcaga agagaaataa aaaaatcttc 147540 tagagagttc agaacaggga tgttgattca agtttatggg gattaggagt ggctggtaag 147600 ggaggcattc aggcaaaaga cataaaaatg cagtattccc ctcgcactca ttaggatggc 147660 tactatatta gaaaaagaag agagtaagtg ttggagagga tatagagcaa atagaaacct 147720 tgtgccttgt tcatgagaat gtaaaatggt gcagccactg tggaaaacac tggtgattcc 147780 tcaaaaaatc aaaatagaat tatcatatga tccagtaatt ctacttctgg gtatatatct 147840 aaaagaatta aaaatctggg tcttgaagaa atatttgtat actcatagtt atagcaacat 147900 tattcataat agccaaaaag tagaagcaat ccagatgtct atagatggat gaatgggtaa 147960 acaaagtctg tgtagtatat acagacaatg gcatattagt cacatcatgg accttcagga 148020 cattatccta agtgaaatat gctagacaca aaaagcaaaa gtagggtttc acttaatgag 148080 gtatctagaa ttgccacatt cacagagaac aaaagtagat tggtggctgc taggggatag 148140 gggaaggaga aaatggggaa ttattgttga atgggtatgg agtttcagtt ttgtgaaatg 148200 aaaatgttct gaagactggt tgcacgatga tgtgagtata tctaacatga ttgaattgat 148260 gaacacttaa gcgtggttac gatggtaaat tttgtgttat atatatctta ccacaattta 148320 aaaaatatag cattttatta tgtaggcgtg ggtgggaaga tacttgacac attggaactt 148380 ctggccatgc gtatactgtt cactcactta ttccttcatt cattcaacaa acatgtattg 148440 aatgcttgct atgtgctggg cactgagcta gatataacaa ttaataaggc ttataagaca 148500 ttgaatctat caatttcatg cttgctaaat atctactccc acctccaaag gcactaagct 148560 tctacagtta gatattcata gctgcttcct actgacttga atcatgcata ggatattagt 148620 aaacaagcaa taaaaagatt tgaggttgat gggggtgggt tcaacagcat ggtggtgaaa 148680 tggaaagaga tgggtaacag aatatgaact agaattgaaa actgtgagcc agtgctctct 148740 aatgaacatt aaaaaataaa gaattcctat ttgaggctgc caacctcaga actaagttat 148800 ttagaatgga cgaaattggc aaagtcagac gtactcaacc caaggagcca atattttgtg 148860 aatattatgg caaatgtagt ttgagaacca ctaccacaaa attgtgaacc ataataatga 148920 ctgagaaggc agggagaggt tatacaattt gggctaaaag gaaagacagg gcttgtgaag 148980 gggagcgcca gtgaaagtca gtgtggttcg ggtatttggg tggggactgg aagcaggaag 149040 cttgagcttc ctttgccaag agaccctgct ggaagggcta tcatcaattg actttagctc 149100 atcttaggat tttcattttt taaaaaatgt tcacaggaac cttcactcca tctatacttt 149160 caatgtctgc ctacctttct ttcttataca actttgaaca ctctctccat tcatttaaat 149220 atattatgga gtgccaacta catgccaggt actgtgctgg gctcttattc cacctttatt 149280 tgattgcaca tgcctgccaa gtcctgggcc aatataacat ctactcctat gtctggtctg 149340 gcgagagatg caaactcatc ttcctctact ttccttacct ccttccttcc agtcttcttc 149400 aagttgtctt cattgaggca atttctttta cctgtgtttt taatcccaac tcctctagtt 149460 tccttcttgg ctttattctt ttatcttcct ctttgtgctt tcaaacattc cctttctcct 149520 ggcccatgcc cttcagtcta cacgaggcct tctcaagtct cttcattcta aaaaattcat 149580 tttcttgggt cttatattct tcagctgcca ccctatctgt atcttttcct attctcctcc 149640 aagttctcaa aggaatgcct tccctcattt tcatctcctt acattccatc tgctgaattt 149700 tggcttgtgc ctgtacctgt ctaaggaaac tccttgctaa gagtctgctt tgtcaggtct 149760 gaattcactt aaccagtctt tgctttgttg gacttctctg ccccatttgc cattcttgat 149820 catcctctcc ataaaccttt ctacttaaag cattttactt ccttattttc ttggttttcc 149880 tagaatctcc ttactgttca ttttcagctt cctttctgtg ttcctcttct cttcctacat 149940 ttttttttag ctttctactt tcttaaagca ttttacttcc ttattttctt ggttttccta 150000 gaattttctt actgttcatt ttcagtttcc tttctgtgtt cctctgattg tctctctttc 150060 tacatttttt ttttctgtgt tcctctgatt ttcacgcagt ctggagttgt catgatcaat 150120 catagcctac tgcagcctcg acatcctagg ctcaagtgat tctcccacct cagccttaca 150180 agtagctagg actacagtca cacatcacca ttctcagcta atttttttaa gaagcatttt 150240 tatagagatg gagtcttgct atattgtgca ggctgggctc aaactacagg gcttaaacaa 150300 ttctcctgct ttggcctccc aaagtgctgg gattccaggc atgaaccacc atgctcagtc 150360 tctacatgtt cctaaagagg agttttgaat attgaagaac agtattttca aattacatta 150420 ttcaagttat aaaaactgat atccagggtt atgtggcaat gacgtaaaaa tttgaattgt 150480 tatttttttg acacatgttc tgtgttgtcc atcagttcat ctgagttcca aatgtcccag 150540 ctgttttatg ctttgtctct gtttcccaga gaccctgagt gtggtctaga gttgggatga 150600 gcattggtct ctaatggttc tgaaataatt gtatattcct gcaaaaacat taagtctatt 150660 agaaaccagc taatttcatt ttgtcatttt tataggtaac atattctggt gcaggtagta 150720 tgtttttaaa acaagtttgc aataaacaat ttcccctcaa ggttaatata ataggcaaca 150780 ccttttgctg caacagacgg caagaggtaa tgaaagatta gcttacatta tgattcatta 150840 tttcaaaatg tcaggataaa gtggatctgc tgcatctccc agagagtgca tgttttgctt 150900 ttctaatgtt aatggattta ctgttttttt ccccccaggc caaattcaga taatcgacgc 150960 cagggtggca gagaaagatt ggccagtacc aatgacaagg gaagtatggc tatggaatct 151020 gccaaggaga ctcgctactg tgcagtgtgc aatgactatg cttcaggcta ccattatgga 151080 gtctggtcct gtgagggctg caaggccttc ttcaagagaa gtattcaagg taatagtgtg 151140 ttgaaaacga cttctatttt tgatcctatg agcagatcct aagagccaaa gcgactgagg 151200 aaggaagaca tagaatcagc catttgtaca aaacatgaat ccctagtagg tccactagta 151260 tctttggtag aaacatggag aagagacagg atctcaggag aaggagttga cacatggcag 151320 ggcagctgag gctgagtaat tccgcttcct tcctttggca agactcaatc agtcttgagc 151380 aactctacag aagaattcca ctagctggat ctctgaggaa aaaagaaatg ttgtctgtgc 151440 cctgactggg gaatgccaga tggacattca tgtttggtag gcaactttgc ctatatgatc 151500 tggtatatgc tgttaattgt ccatgcataa ttatctctct actcaggcct tgtccaggca 151560 aatattctgt tttgttctag tttagcttgt tctccccttt ctctcttcca tctctttctt 151620 gtctcaatgg atgacaggat attttgctat gagctgactc agtggttggt gtcttgtaat 151680 ggggagatat catctttatc aaacagttat taagtatcta cctgtagcat ttcattttcc 151740 cgcctgcctc cattgttttc ttgtctatag tttgccaatt atagctaata tacggagagc 151800 tatactttat ttctactcca gaaatgtctc tattattgca ttataatagg ataccctggg 151860 gaaacactaa tcatttttac tacctaaaat acctatgctg aatatccttt atctgatagg 151920 aacagagggg tatcctctag agtcgcacct atgcaagctt gcactcnnnn nnnnnnnnnn 151980 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 152040 nnnnnnnnnn nnnnnnnnnn nnnnnnaaaa gctcctagaa ctgattaatg aattcagcag 152100 agtttcagga tacaaaatta atgtacacaa atcagtagct ctgctataca ccaacagcag 152160 caaccaaggt gagaatcaaa tcaagaactc actccttttc acaatagttg caaaaaaaaa 152220 aaaaaaccaa aaaaaacaaa aactaaccaa gaaggtgaag gacctctaca aagaaaacta 152280 caaaacacct ctcaaagaaa taaatcatag atgacacaaa caaatggaaa cacatctcat 152340 gctcatggat gagtagaatc aatattgtga aaatgatcat actgccaaaa gcaatctaca 152400 acttcaatgc aattcccatc aaaataccac catcattctt cacagaacta gaaaaaaaat 152460 cctaaaatta atatggaacc aaaaaagagc ccacatagcc aaagtaagac taagcaaaaa 152520 gaacaaatct ggaggcatca cattacctga tttcaaacta tactataagg ccatagtcac 152580 cgaaacagca tggtactggt ataaaaatag gcatgtagac caaaggaaca gagtagagaa 152640 ccgagaaata aacccaaata cttacagcca actgctcttt gccaaagcca acaaaaacat 152700 aaagtgggga aaggacaccc tattcaacaa atggtactgg gataattgcc aaaccacatg 152760 taggagaatg caactggatc ttcatctctc actttacaca aaaatcaact caagatggat 152820 caaggactta aatctaagac ctggaaccat aaaattctag aagttaacgt cagaaaaacc 152880 cttctagaca tgggcttagg caaggatttt atgaccaaaa acccaaaagc aaatgcaaca 152940 aaaacaaaga taaataagtg ggacttagtt aaactaaaga gcttttgcac aaaaggagca 153000 gcagcagagt aaacaaacaa cccacagaga aggagacata atctatacat ctaacaaagg 153060 attaagatcc agaatctaca aggaactcaa acaaattagc aagaaaaaaa acaaacaatc 153120 ccatcaaaaa gtgggctaag gacatgaata gacagttctc aaaagaagat acaaagtggc 153180 caacaaacat atgaaaaaat actcaacatc accaaagatc agggaaatgc aactcaaaac 153240 cacaatgcaa taccacctta ctcccacaag aatggccatt ttcaaaaaat caaaaaataa 153300 tagacgttgg tgtggatgta gtgaaaagcg aacatttcta tactgctggt gggaatgtaa 153360 actagtacaa ctactatgga aaacaatgtg gagccacctt cttgcttgat ccctcactcc 153420 taaatctctc tcctctaatc tatgagaaca ccaggatagg ttcaaaatta agaaagtcac 153480 ttctctgctt aagatccttt atggttccca tatccctcag ggatctcaaa ctcctggttt 153540 gacagataaa gacttctatg ttggtactgc agcccagcct cagctccagc agcctcctta 153600 agcacagatc acatggtcaa atgagcacta aaatctggct ggtccaaaat aagatgtaag 153660 tgtgaaacac ttggaggatt tggaagtctt agtgaaggaa aaaaacatac ataatgtatc 153720 aataattttt aaatgttgat tctgtattga aatactattt ggggtatatt agttaaataa 153780 aatatatcac aaaacttaaa aaagtaataa tgattagtct tgtaaagcaa gcgtttaaaa 153840 atataatcac ctaaaatata aaaaatataa attttatata taaaatataa aaaatataat 153900 cacctaaata taattctgta tgttcctcac caatttttat ttgctgaatc aagcataaac 153960 taaaccatgt attatctcca ggcatgacca gaacatttct tttctttttt tgagatggag 154020 tctagctctg ttacccaggc tggagtgcaa tggtgccatc ttaactcact gtaacctcca 154080 cctcctgggt tcaagcaatt tccctgcctc agcctcctga gtagctggga ttacaggcgc 154140 tccccgccat gcctggctaa tttttttttg agacagagtc ttgctctgtc gcccagtctg 154200 gagtgcagtg gcacgantct tggctcactg caagctccgc ctcccaggtt cacgccattc 154260 tcctgcctca gtatcccgag tagctgcgac tacaggcgcc gccaccatgc ccggctaatt 154320 tttttatatt tttagtagag acggggtttc accatgttag ccaggctgct ctggaacttc 154380 tgatctcaag tgatccaccc agctcggcct cccaaagtgc tgggattaca ggcgtgagcc 154440 atcatgccca gccaatgaga acatttcttt ataaacaact ccctctgctc ttcatcatag 154500 gatgtctctt aaggctgaca tatatttctg taatttccaa aaagactggc ctcaagtgtg 154560 ttggtttata cctactggat aagttttcaa gcagacataa ccagactagc ctatgcgata 154620 tttaatcagg aactttccaa aattcattat cttttttggc ctcttccttt ctctttccac 154680 aaggcagaaa ctagaaagtc tcaccagctc ttgggattcc agtcttagtc atgattatta 154740 catctctaac agaaaaaaaa aaaaaaaaaa gcttagttat cttttcagag tcctgcctca 154800 acaaacttga tttttgaatt ttttctttta tgttgctggt gatttatagc aatatatggc 154860 catcttctca tttcactatc atgaaagcat caaactcatt tttgtgactc tccattcaga 154920 agagattcac tttccacaat gactagtgaa gacaataact ctgcccattc ctaccggttt 154980 ttacagttgc ccgcagttgt tctaaattga gcttgaaatg taaatatgat agctgcggca 155040 gttgctccca acccccaata tacacttgta tatactacct ttagctttgg attctaacca 155100 ttccattgtt aatctgaact tagatcataa aacataaaat ttaagatttg aaacatactt 155160 cagctggcat ttttcagaag taaaaactga gtgaagaaaa agtatgtgat ctgcccaagg 155220 ttcctaggta gtaggtaaag agtcaagttt aattgcacgc ttggccctta gctgggactc 155280 ctatttgaca aaatgatgtt tttatatacc agaatgggca ttttaaaaca aaatcagact 155340 ttcaaaaata gaattatcta aaaacaatta aaaccttggc tgaaagataa aaatgcccct 155400 tttaaattat attaaatatt aaataatatt aggtaattaa atcttaagta ggtcttttta 155460 aagtatctgt gacaccgtct atataaattt attttggtac ttctgctgtg caactaagcc 155520 aacatatgat tgatgttttt gttgaagagg agtaatatcc tgtgcccacc gtaacatttc 155580 ctaagtcaca gttttggttt atgggatatt aatatcttac tcatgcatat gtctatctct 155640 catgacactt tatgttacta acaggtcagc caggcagacg cataacaatg aaaggagcat 155700 taaaccatgg gtcaggagac ttggtttcct gtctgagcag ttaacttagc ttagtgattt 155760 ggaccagaac aatccaactg aaaaacaaaa aggtgcacta gatgatcttt aagttctttt 155820 cagctctaaa aactacccat tagcctgatc acaaccactg aaacaaacaa aaaaaagcat 155880 atggaaattc ctggggactt acagaatttt aaagtagcaa ttcattcata taattactgc 155940 cccaaagttc tgcattttat aggttctatc tacggaaaaa gtccttacat catatcaaga 156000 atcatttatt tttgcaaaag aaaattgtac aaacaagata aaccctttct gaaatttttg 156060 cctggccttg agtcactgcc agcatttctt gtaacattca aggtaaggtg agacgtggtc 156120 attcctgaaa aggtacataa agatacctca gttttcttct gataggaatc aaaattatct 156180 ctaaataagc aatcaaataa attgagtatt aaaaaattaa tcaaagttat gttataaaca 156240 gttgaacata gcctggtata actataagat cttttatgta agccttatgg taatcacaaa 156300 gcaaaatcct gtagcaaata tacaaaaggc aaaaagtaag aattcaaagg ataccactat 156360 agaaaatcgc ctaatcacaa aggaagacag caagatagga agaaagagat acagtgagta 156420 aatggattta aaaaaacaag accctgttat atgatgtcta gaagagattc aatgcatggt 156480 taagaaaaca cagagaatga aggcgaaggg accaaaaaag gcattctatg aaaatagaag 156540 ccaaaagaaa gcagagacag ctatatttat atcaaataaa ataggcttta agtcacaaac 156600 tataaaataa gacaaagaag gccattaaat aatgacaaga gggtcaattc attaagagga 156660 tataacaggt gaacatacat atgcacccaa cattggagta cctaaatgaa tgaaacaaat 156720 attaattgat atgaaaggga agatagactg taatacaata atattgggga actcagtacc 156780 ccacttttag caatggacag attattcgga cagaaaatca ataatgaaag ttcaaactta 156840 aactatactt tagcacagat ggacttaaca gatacataca gaatatttca tccaacagca 156900 acagaacaca cattcttctc aaatacacat ggaacattat ccactgaatg ttagataaaa 156960 cagtatagat catggcctgg cacggtggct cactcctgta atcccagcac tttgggaggc 157020 taaggtgggc agatcatttg aagtcaggag tttgagagca gcctgaccca aatggtgaaa 157080 ccccatctct actaaaaaat acaaaaagtt agccaggcat ggcggtgtgc tcctgtattc 157140 ccagctgctc gggaggctga ggtatgagaa tagcttgaac ccaggaggcg gaggttgcag 157200 tcaaccaaga ttgagccagt gcactccagc ctgggcaaca cagtgagact ctgtctcaaa 157260 aaaaaaaaaa gaaaaaaaac agtatagttc atatgttagg acacaaaata agtcttaata 157320 aatttaagaa cattgacacc atatcaagta ttttttccaa ccataaataa tatgaaacta 157380 taaatcaaca agaataattt tggaaaattc acaaatactt gaaaataaaa caacatactc 157440 agaaccaacc agtgggtcaa agaagaaata aaaagaaaag ttgaaaaata tcttgaaaca 157500 aatgaaaatg gacacacaac ataccaaaat ttgtgggatg cagcaagagt attttcaaga 157560 gggaagttta tagcaataaa tgtcttcatc aaagaagaag atctcaaaca atctaatgtt 157620 ataccacaaa taactagaaa aataaaaata aactaagccc caagttagta gaaggaagaa 157680 aataataaag atcggaggaa aaataaataa aattgagact aaaaacacaa aacaaaagat 157740 cagtgaaact acgaatttgt ttttaaaaag ataaacaaaa ttgattaacc tttaactaga 157800 ctaagaaaaa aagtgagaag acacaaataa actgaatcag aaataaaaga ggagacatta 157860 caactgatag cacagaaatg caaaaaatta taagagtact atgatgaatt acacaccaac 157920 aacttggata acttggaata aatggataaa gtcttagaca cataaaccta gcaagtctga 157980 atcatgaaga aatagaaagt ctgaccagac caatagctag aaagaagact gaatcagcaa 158040 taaaaagtcc tctatggaag aaaagcccag gacctaatgg gctttattgc tgaactctac 158100 caaatattta aagaactaat accaatcctc aaactcttcc caaaaattga agaggaggga 158160 atacttccaa actcatttta caaggccagc attactgtga tactaaagcc agacaagggt 158220 attacaagaa aattaaatgt catgccaata tccctgatga atatagatgc aaaaatccac 158280 aacaaaatac tagcaaaatt gattgtcatg acatgaaaaa gaatcattca ccatgatcga 158340 gtgggatttg cccagggatg caacgatggt tcaacatatg caaatctata actatggtac 158400 acacattaac agaatgaagg acaaaaacca tacaatcatc tcaatagagg aaaaaatgca 158460 tttgacaaaa ttcaaaatcc tttcatatca aaaactctca acaaattaaa tatagaaaga 158520 gtgtacctca acacaataaa ggccatatat gacaagccta cagctaacat catactcaat 158580 ggtgaaaatt tgaaaagtct tcccctaaga tcaataacaa gacaaggatg cccactctca 158640 ccacttctat tcaacatagt actgagagtt cctgccagag caattatgca agaaaaaaaa 158700 taaaggcatg caaattgaaa aagaagaagt taaattgccc gtgtttgctg atgacatgat 158760 cttacacata gatcatgtaa gtatagactc cacacaaaaa actattagaa ctaataaaca 158820 aattcagtaa agtttcagaa gagaaaatca acatacagaa atcagtagtg tttctataca 158880 ctaacagcaa actatccaaa aaaagaaatc aagaagaaat ttcatttata atagctataa 158940 aaataaaaca aaatatttgg gaataaattt aaccaaggaa gtgaaagaat tgtatgctaa 159000 aagctataga catcaataaa agaaactgaa gaagacacaa ataaatggaa agatatacca 159060 tacatagact ggaagaatta atattgttaa aaatatccat atgacacaaa tcaatctaca 159120 gattcaatgc aatgcctatc aaaattgcaa tgacattttt tacaaaagtg gaaaaacaat 159180 ccaaaaattt gtatggaacc acaaaaaaac cctgaatagc caaaacaatc tggagctaga 159240 agaacaaagc tagaggcata acactacctg actcaaaata tactataaag ctatagtaat 159300 taaaacagca tgtattgacc aatggaacag aatagagaac ccagaaataa attcattcat 159360 ttagagccaa ttaatttttg acaaagctgc taaaagcaca caatggagaa aggacagttt 159420 ctttgataaa tgtttctaga gaaactggat atctacacac cgaacaatga aattggacac 159480 ttatctcatg ccgtatacaa aaatcaactc aacctggatt aaagacttaa atgttagacc 159540 tgaaactgta aaaactacta ggaaaaaaaa aaccagctta agaacatggt ccttataggg 159600 attgttgtgc tgcctacact catgcttcct ccagctgaac tgacagtcac agaggctgac 159660 ctgccttcat ccctaatagg taatggaggg ccttgatttt catacctaga ggatgaagga 159720 gttagattag atcagtggct tgcaaactgt gttccttgga gccctagggt tctaagaagg 159780 tttctcatga acatcataat gaataaagag agggtatgcc aaatcaactt ttatctgttt 159840 catagatgac gatctgcttc tgcttgtgga aaccagagct tgattgatat aaaatactgt 159900 caaacattgg attcattagt ctttaaggtc catatgtgat tcacttactt gattcagtat 159960 atttgtttgc aaataaaaaa ttataatatg gggagttttt aataaatatc tattatatga 160020 attaataaaa taatagtttc aatatcataa atatatagat tagattactg cttaaaacaa 160080 ccagtctctc tttggtaaag agcagctagc ttttctttaa catttttctt aaattcaatc 160140 ctaaatagga gcaccccaac ctaccttttg aggaaacttg gattcacatg cagctacaat 160200 cttcacaatt attcgggcat cgaaaaaagt aattcacatc tacattttta atttattaat 160260 ttgattctac catcatgaac attaataatt ggttgtatac tttttttttt ttttttgaga 160320 tggagtctca ttccgtcacc caggctggag tgcagtggtg tgattttggc ctactgcaac 160380 ctccgtctcc tgagttcaag caattctcct gcctcaggct cccaaatagc tgggattaca 160440 ggtgggcaca actacaccca gctaattttt gtatccttag tagagacgag gttataccat 160500 gttggtcagg ctggtctcaa actcctgatc tcaggtgatc cacccgcctc ggcctcccaa 160560 aatgctggga ttacaggtgt gagccaccat ggccagccgg ttgtttactt ttgataaagg 160620 atagccaatg taggattaaa gaggattcca atcgcagtcc ccaggttggg agtttatcca 160680 tcaataaagc aaattacgat aactcatagt gataaatatt aaacccaagc aacaggaaaa 160740 tattttattt tccagtgttt cattgggctt ctgaatcatt ctggacacat gtatatttcc 160800 ctgtctatat tagtagtatg ttattttctc actttaaaat tatcccgtta atttttggat 160860 ttatttgtta ttttggaata tttctaaaaa ttatactgca acatttgtta ttaaaataaa 160920 taaagactag ttgacaatta ctactttatc tcaaatttct tcttaatgtg ttataaggaa 160980 acataaccag aatagtcagt ccaagagtcc tgcacatcaa ttgatttcta tgtgccaatt 161040 tcctcactgc acaatgaaaa ccttgcctca aacacgcctc tgaatctatg gtaagaaaaa 161100 acctttcaca aattcgtgta aatctctggc atcataaaat gataaataac acatctcact 161160 tgtcattcag ctatattcag catatgagat cagaaaagaa aaaaaagctt aggtgtttaa 161220 gccaagtttt tattctccac aaagaaatta gaaatttata tcttgtagaa gtgatgaaat 161280 tgccattctc tttctttcag ctgaaaaaaa aaacccagca gtgctcgtat atgatgaaat 161340 ttttaactaa gatagtaatt atttttaaga caaaaaagat atgtaatagc taacacttgt 161400 gtggcacttt agatttatat tttcccatgt tacgatttgt catcttcatg acaaactcat 161460 taagtaaaat ttatttattt gtttatttat atatttattt ttgagacaga gtctcactct 161520 gttgcccagg ctggaatgca gtggtgcaat ctcggctcac tgcaacctgt gcctactggg 161580 ttcaagtgat tctcctgcct cctcctcctg agtagctggg attacaggct tctgccatca 161640 cacctggcta attttgtaga gacgaggttt caccttgttg gccaggctgg tcttgaactc 161700 ctgacctcag gtgatccgcc cacctcagcc tcccaaagtg ctgggattac aggcgtaagc 161760 caccgtgctt ggacaataaa atttatttat ctccatttca tatttgaaat tagtgaagct 161820 cataaaagtg actttaacaa ggttgttcag caagtttgag gaggagccag catttgaaca 161880 catttatctt tggaagagtt cctctttcta ccaaactcag caaaaaggcc acattcttga 161940 gtaataatat atgtcttgga tgtcaggtgt ctgagtaata ctctgagttg gactaaacct 162000 gggagtggtt gtttaaagct ctagactccc attctgatca ttcaatattt gagccatctt 162060 gcaacccagt ctccacttgc cgttgagatt tttatttgcc gcttcccatg caaatgttct 162120 ctttatactg tgaggacatt gagggaaggg actacaatct tattcatatt tgctttattc 162180 ccaagggttt gcatataaga agccctacac aaataactat ttaaatgaat tgaatcaatt 162240 cattaattag tgcaaaaaaa tacttcttga acacctacct tgtgacttgt ttcatgcaag 162300 atcggtaaac aagacacaga gaccccccac ccccgcgcca tcatggagtt tatggaccat 162360 atgtaaagac agacattgaa tgactaataa taatggtgat aagagctaag agaagagctg 162420 tttgccatta aagctagaac atgaattttc cagcaccttg attttgaact tcgagcctca 162480 ggaactgtca ggtaactgtg taggccttcc tgaagaagag acatgtaatc tacaacctaa 162540 agttcaagag gaaggagaca aatgaagagg aaaaagcaat gcagagaaac cagcacatgt 162600 actaggatag aaaagcacat tcccgaaagt gcaattcaaa tcctgcatct tatagaacta 162660 ccatgattca gaaccaaatc taataatgat gctgggattt tcagaggcag taagtattat 162720 aacagattaa aattgttagt tcatggagac aaatcatgca ctcttttgga tctttacaat 162780 agatcttcag tgaatttttt cagccttgct atgaaaatag ggagtaggtc tgtggttctc 162840 ttttaactga aactaaactt tttatttcat aggtagagtt tcaatatcct agttggtaac 162900 cagcctggtt aagaaagtgg attgttgtga accctaatgg ttgaaaacat gttgtaaaga 162960 tttattcagt cacagctggc ctttgccatg tgactgcaca ttttatagtt agttatcatt 163020 gtacttccag ttgtaaatta aggctttatt caatgggatt tttcaaggag ttgttataga 163080 gggtatcctg tggccatgtg tggtattcca tgttgtagaa aatacaataa attatattga 163140 tttatggcaa gtactttata catatcatta aaataagatg ttctcacggg ctataatttt 163200 atgaatttaa agcttcattt aaaacttatg tacatataaa aactgccaga aagatacatg 163260 ttttccttac atgtaaagaa atactgaaca atcactgagt aacccctatg ggatattgcc 163320 acatactgaa ttgtgtaccc ttaaaactca tatgttgaaa tcttaccccc tgggcctcag 163380 aatgtgactg tatttggaaa ttgtacctta agtgaggtga ttaagattca atgaggtcct 163440 gtgtgtgggg ccctaatccg atatgactgg tgtcttcgta agaagaagaa gaagctgtgg 163500 atgccccgag aaaaggccat gtggggacac agagagaagg cagccatctt caagccaagg 163560 agagaggcct cgggaaaaat caaacctgcc aacaccttag tctcagactt cagcctccag 163620 agctatgagg caattgactt ccgttactta agccacccag tctatggtat tttgggaggg 163680 cagcctgtta tgaactgtgt ccccacaaaa cttgtatgtt gaagccctag cccctggtat 163740 gactatattt ggaaataggg cctttttggc ggtaactaag gttaaatgag gtcataaggg 163800 tggactccta atccaacagg gcttgtgaga agagaaagag ataccaagag tgctcggacg 163860 cagaggaaag gccatgtgag gacacaggca gaagacggct agccacaagc ctagaagaga 163920 ggcctcacag gccgggcatg gtcgtcacgc ctataatccc agcactttag gaagccgagg 163980 tgggcggatc acctgaggtc aagagttcaa gaccagcctg gccaacatag agtgaannnn 164040 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 164100 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnntttt cagaccggga aggccggcaa 164160 agaagccgct taacttcccc aaaggggcgt cagggcagag gcgctcccca catctcagac 164220 gatgggcggc agggcagaga cgctcctcac ttctctagat gggatggcgg ccgggaagag 164280 gcgctccatc acttcgctag atgggatggc ggctgggcag agacactcct cactttccag 164340 acctgggcag ccaggcagag gggctcctca catcccagac gatggcggcc aggcagagac 164400 gctcctcact tcccagacgg ggtggccccg ggcagaggct gcaatctcgg cactttggga 164460 ggccaaggca ggctgctggg aggtggaggt tgtagcgagc tgagatcacg ccactgcact 164520 ccagcctggg caccattgag cactgagtgc ggttttgttc attttttaaa ttcttttttc 164580 tttgtctttg ttggattgag ttaatttgaa aaccttgtct ttgagctctg aagttctttc 164640 ttatgcttgt tttattctat tgctgagact ttcaagaaca ttttgcattt ctctaagtgt 164700 gtccttcatt tcctgaagtt gtgattgttt tttatttata ctaactattt cactgaagat 164760 ttctcccctc atttcttgta tcattttttt gacttcctta aattggactt cacctttctc 164820 tggtgcctcc ttaattagct taacaatcga ccttctgaat tctttttcag gtgactcagg 164880 gatttcttct tggcttggat ccattgctgg tgagctagtg tgattttttg aggggtatta 164940 aagaaccttg ttttgtcgta ttactgggat tgtttttctg gttccttctc atttggtagg 165000 ctatgtctga gggaagtact agggctcaag gctgctgttc agattctttt gtcccacagg 165060 ttgttttctt gatgtagtac tctccccctt ttcttagaga tgtggcttcc tgggaaccga 165120 cctgtagtga ctgttatttc tcttctggat ctagccattc agcagggcta ccaggctcca 165180 ggctagtact gggggctgtc tgctcagagt cctgtgctat gggctgtttt caggtctcac 165240 agcgttggat tccagcacct gctctgatag aggtggcagg ggagtgaaat ggactctgca 165300 ggggtcctta gcttttgttg tttaatgcac tatttttgtg ctggttggcc tcctgccagg 165360 aggtggcact ttcaagacag cgtcagctgt ggtagtatag ggaggatcag gcagtggcca 165420 gggccttaga actcccaaga gtatatgacc tttgccttca gctaccagga tggataggga 165480 atgaccatca ggtggggcaa ggctaggact gtctgagctc agactctcct cgggtgagtc 165540 ttgctgaggc tgtgctgtgg ggcagggggg tgaggttccc aggtcaatgg agttatgttc 165600 ccagaggatt atggctgcct ctgctgcgtc atgcaggctg tcaggaatgt gggggaaagc 165660 cggcagttac aggcctcacc cagctccctt gcaaccccca aaaccggtct cactcctgtg 165720 ccctaccaac agcatcaagt ttgtttgcag gcagcggatg agcaaggcta agaacttgcc 165780 gcagctacca gcctcccagc aaagaatgta agtagggctt tcatgcctcc cttcctgttg 165840 aatctgtaca ccaaattcac tccctccccc aagttctggc caggtgactt catgtttggt 165900 tggaattgtt acaaagttca gctggaggtt tccttctcgc tgtggtcttt tcccagttcc 165960 tctggccacc ctccccaagg acccctgtga gacaaggtag aaatggctta ttaggggacc 166020 cagagagccc acagggcttt tccccttgct ttctctaccc tttatttcac tcagctgtct 166080 aattaaatca gctccaggta agttcatatc cttctcccat gatctggagc tgcagattcc 166140 ccagtgaggg tgtgtgttcg ggggtgggct atcccccttt cctactttca cagcttgggc 166200 actcacagta tttggggtgt ctcctgggtc ctgtaggagc aaactgcttc cttcacaggg 166260 tctgtggatt ctcttggctt tcctggtata ttcctgtagt agttctggag cagaagttta 166320 tggtgtgagt ttccacacac tgctctgttc atccaagtga gagctgcaat ctagtcctgc 166380 ctcctttcca ccattttttg gccttgacgt attacattta ttttatgttt gaagttttgg 166440 cagttttatt ttgaaaattt tacataacaa atgccaagcc aaatccaaac ttcttggcct 166500 aaatcattta cagataacct ttactgagca tttactacat gaaggtgttg ttgacacagg 166560 ggatttaaga tgtgatcact gaccacaaca tccaggcaac ctaaaagtga aaagaggtca 166620 ttcacaaaaa ataggaccaa acttcctcca ttcctcaagg gacctaggac tggagttggc 166680 ctaaaaattc ctgctgtatc acctcaccca ccagttttga tcttgctctc agggatcaag 166740 gaagctcaag gtttctggcc cttttggctc atgttcttgg aggtatattc tattgtcaag 166800 ttaaagtcgt acccatccta gatctgtttc tctctctttg tggttccagt ctcatagaaa 166860 acataactat gtgaaaacac caactacccc ataaagctat tctgagactc aaagacatga 166920 actctatttt gataatcaca aattgatgta tagatgtcag atatcattca tgtattatgt 166980 agcattgtgg tttaagtctt agctgttgga atcagactac ttgcattcaa attttagctc 167040 tgttgatagg tgtgtaacct tgaacaagat acgtaacctc ttcagacctt tgtctctttg 167100 tttgtcaaat aacgacaata ataatactaa cttagtaagt atgtataagg aggcatgtaa 167160 agcttctatt gtatttggct tatggtgagc ccttcatata aattggttac aatgggtaat 167220 gaaaagtacg ttcaattttt cccacaagga tttaatctaa tctctaaata aaatgccagt 167280 tttagtatac tgtcatcatt ataaggaaac tataattctt aagtaattaa ttactttggt 167340 tccctttgga taattagtga tacataaaat gcagtacctt gccctgagga acctacaagt 167400 tagcctccct ctaatcctgg cattcaaagt cctccacctt ccgaattaca cctgtttttt 167460 caggcattgt ctcccacttt cctagcaagc ctttggctcc aggaaactgt tctgttcatt 167520 gacgacagaa tgtattttgt cccgtatgcc tcccttcaat ctgaagttca tttttagtaa 167580 ttttttttat tagtagtgac tttccccatt tactaatgcc tttctcttta gctcatttag 167640 aattccctgg aagtcatcat gttttccttc tgaattgcta tcatattctg tctctgtgtc 167700 taatcagaaa gttaggtgag ctgctgtctc agctcctgtg ttaatccagg tactgagctc 167760 tttgtaccct gccagcttga gggcaacttg gatgcgctgg tgtgtagtga tttgcaactg 167820 tgagagagcc gtttccatca acaagtgaca gcttttggtt ctaaacactg cttgacctca 167880 ttctggtttg aacatatact ttggcctctg ccctctacct cacctccagt tctgatcttg 167940 ggcatgccac agaaccccat ctacactagg ctttcatttt ggacttctaa gtcctttact 168000 tgaccactta ttttctttaa ttgctagact taatcatcca tgcatatgac agccactcag 168060 ctctgacccc aatacttcat tgaggctcat gccagtctga cctctcacag ggaagagcac 168120 cctgccggtg acccctggcc cttggattat gctgtcccac cagtgcccag ctggctgctt 168180 ggcactgcat gtgatgtatc tttgtttatt gatcgcttaa ttgaatggga tataggatta 168240 tattccatgt tccagatcaa gttgagccaa gctgacaact tagtattaaa aaaatatatt 168300 tatctcctat ctgtccaatt aaaattttaa tttctagagg tagagacagt cacattgcta 168360 tttaattcct agcacagcag tatttttgtc aatatttgtt attagtggtg agtttaaatt 168420 ataaaggaaa aaagagaagt ggtgatttat gtcagcgctt ggctaaacta ttcccttgat 168480 ataagtctat tattcaggtc acataagcat gactgaagta atatcacaac cataatatca 168540 taattatctc tcttgctgtc tctgtcactt tctcactttt gtttgtgcat agtgcataga 168600 cctgtagaaa atttattagt aatctgaagc ataaaaccaa atattacaac tatcataaca 168660 aataaataaa actgtgcact cctttaggga gtagtaaagc catttctaaa attaagtcaa 168720 agtaagattc ccttattatt gagatatttt agtggtatac actatcataa gtaagatgaa 168780 taattttgtt agcagctgac actgctatat agatatttat cttgggaagt tctcagtgta 168840 acatctttac tgtgtttttc tctttagatt atacttttat gtttattatt ttgtttcgtg 168900 ggggattcaa aaatatgcat tttatgccat acttggggat tccctataaa ttattagttg 168960 taatatgaca gttccatcat gaattttcca ggtattcttt tatgcaagca gataatagct 169020 cattttggtt tttaacacat tcatgcatat tctttctctc tcaataaata tggttttaat 169080 ttattaaatg aaagatttaa aaatgtgcta agcattttaa taataatcga ttttggatta 169140 acttgttatg tttactctag ggctgtagtt caccatttat tcagttaagt ccttccccaa 169200 attcaatatt gaacatgtgg aattgattcg tttcacgtgg atgtatcatt tactcccaag 169260 atgttggttt ttggcattta gtactggtaa tgggccagga aagtgctcat ctatatttgt 169320 tgttattcac tgattgcatc ttgcccttgc acccactgag acgatgggaa agtagcaaca 169380 atactaggtg atttctttga tttaaaccca attaaaagaa ttagagagtt gtctgataca 169440 aggccaaaga actaagaaca gaaacaaaag caaaacaaca aacagcagca caaactccag 169500 tgagataaat ttttaaaaca ttgggaatat ttaaaaaata aaaacactcc aatgaaccac 169560 ccaggtttta ttaaagagta gagaactcaa acagcagaag gcagagctgg tggaggaaac 169620 tcagcaactg ctcagaaatg aaacaaccta ggaaggaggt gcgagtgacc tgaaactcct 169680 tttaaaaaca gaaaggacaa aaagaggtat gggctgacaa aaggaaagtg gtagattact 169740 gatgtattgc attatgctta gaatgtctca gaatgcgaga ggcagtaaac acaccagaag 169800 aggatacaat atccggacca tgtgcaactg caaataaatg tttgggttaa aacttggttg 169860 attctaaatt acatgaagag ctgatgataa ttgaggcaga actgatagac ctaacaatag 169920 aaaaaaatcg atttaaattc agagaagagg tcatttaaga aagtataatg aagccactta 169980 ataaaaggaa atattcctct aactaaagtt tgagatttag ggcataatcc tcaaagacag 170040 gctaatataa tctatttttt gattaaaaaa aggaactttt ggtttaaagt aagatgttca 170100 gctgctctta gagtttattt ctccatattt gggcatataa gaatttaagg aaaaatatag 170160 aaatataaga aagatttcat gagaatcaca agcatagttt ataggcaaga tagccttttc 170220 tgtttgaaag cgaaaaatac tatttcaaca tgtaaaaacc taagtcagtt ttcactggca 170280 tgtcccacaa tcatgcctga aataatggtt gaagacagat gtgagacatt tcaagggcaa 170340 tagattaata catgaaaccc acttatgcct agcgttccat tattggaacg ctaagcatgt 170400 gggagttatt tatatcctat tgctcaaggt catctccaag gtctgagttt tcactcatgc 170460 aaaaattcaa aaaattgcaa cctcggcgta aatgggttaa caaaaagtta atgctggaca 170520 gtaaaataaa ctactaaatt agacacacca tattttttaa attataagag attaagaact 170580 atgagatatt taaaaagcca cccacagaag tagtaggaca ggtagagaag gataaattct 170640 aacaatcaac tgtatctcca ccccaccttg taaatgacaa attagtttac ttagtcaatt 170700 caggaaatta aacgtataca ttttgtgtta aaacagaaga ctttttttaa aaaagtgtgt 170760 tagttaaggt taattttgac ctagttaaga aaaagcagtt tagagtcttg aaatggaaat 170820 gagaaataca taattaccct taaaaataag ttgatagtga attttatcta ggattcttaa 170880 gacattttta atatttaatg aaaatgaact acacaattat taaaaaatag ttgcctgggt 170940 ttagaaaaat gatcccttaa taagacatat acaacagcct gaatttttat ttccaaatac 171000 tatagcaaca aaataccggc aagaaaaatg cacagaaaca ttggatagtc tcttcttact 171060 aatcttttac agatatttat atattctgaa ttctaacttt taatttattt tatgtattat 171120 aaatgtcatc tagtatgcag cttgactttg ctttatggta tcatctgttt cacagaaaat 171180 tttaagttgt ggaatttatc gtattttttc tttatagttt gtgctttaag acctgtctaa 171240 taaatctttc cttccctgga cgctataaag ttatttgtct atattctgtt aaaaggaata 171300 aaactttgct ttttttcaca ttttgttact tatttcacct gaaagagaat tttgtttatt 171360 atgtgaggta ggaatataac ttaatttttt tccattgaat aaccaaattg tcccagagca 171420 attaagcaat acattctttc cctgttgatc tgtgaagcta cctccattag gcatgaagtt 171480 gtcctgttga agagaatctg attctgagct ctcttcacta tttctttatt tgtctatgtc 171540 tacactaaaa gcaatttaat ttctgtgtct ttataattac tttgacttta taatccttga 171600 aagggacttt gttcttcttc aaaattgttt tggctattta tggctacttt tgctttcaaa 171660 tgagttttta aatcaaactt taatgagatt gcattaaact tataaattaa tctgaggagg 171720 attgacatct tcatgatatt tagtcttcct acccattaac attatataac tctccattta 171780 ttttaggtct ttttgaatga cttctaataa agtttttcaa ttttctccaa aatatcttac 171840 atattaaaat ttactcatag ctgtctcatc ttactgatat tttaaagaca tatcttttta 171900 aaaattatat tattaaattg tttcaggtat gtcttttttt ttgaagtttt acaaatttgg 171960 gattatactg cctcttcatt caacattttc ccatgctgtt ggggatcctt caagtcaaaa 172020 ttattagagg agctgcatta atattccagc atggacatac tataatttat ttaattattt 172080 cccgaattgt atgtttttgt ttctaacttc acagttttca acatgactgg gaacagcttt 172140 tcttgctaaa tccttgcacg ccacagtaat tatctcactg ggccaaaaga taggtacttt 172200 ttcatgactt tcgccatata ttgtcaaaat ggaaccaatg gtgatttgtt cagaaatcat 172260 ggtacatcat ataaaaagat tactctgcaa gcatcacaaa ctgtgatata tagaaatgtg 172320 tttattgaca tgaaatagat catgaagaaa gtgattacaa atggtattta agcattttaa 172380 gttatatagg cttatactga gcaataacaa agagggtgaa taaatgaatg aatatgtgat 172440 tctggaaggg tatgtaacaa aaggttaaca atggttagcc ctgggtaagg ggattatgta 172500 tgacttttat ttccttcttt ttttcttcct ttccccttat gtttttaaca atgtacatga 172560 atcgtttatg aataaaataa aaaactttga tattcttata taggtttagt aggataacat 172620 ttctccttca tttctttcat ttttagaaat ctttcttcac ggaaattctt ttttttaaat 172680 gtttatttct gtctttgagg agtgagattg actggctatc ttttaatacc tgtgtgtatt 172740 atcattattg tatcttgctg ataaatttca caacagttaa ttattttatt ccccatttca 172800 tacttagctc tattttaggc aagttcacaa atatcattga atgagttcat tcaatgtcat 172860 catgatgata ttgaaatgtc aatagcagat gacttgtttc tggggtgtta atatgcctgt 172920 tggttacatt tgtgtttttt ggtgatggaa ggcagccact gaggcaaaca gcaagaatac 172980 agctaagcct ctaactgcat actcttctca ctcgttgctt aaaactgaag cgtggataat 173040 tggtgtgcat tccctaaaaa gttatgtcat gatgcagtag agaaataagt taactttcct 173100 atccctgtat caaagtttct tttgaaggta actgagacag cgccaaataa ggagcagagt 173160 ttctgtgaat catgaaatct ttctaaacaa ttgagaaaaa aaaaactgtt ctgaaacaaa 173220 aacttgtgcc ctatcctttt atttgaatgt gttttcttaa ggccacaact ggcagagatt 173280 tgatgatttt atgtttaaag caattttttt tttttttcat agcaaggagt cccactgcca 173340 tcaggttttg tttttggaga gattctgtaa ctgacatagg gtaacttact ctgatggctt 173400 gctccacatt cactacaagt acatactgtt ctgaaaaatc tcaaagttga aatattttta 173460 tttgggcaac ttctgcaatc aaggtaattc actctatctt tggagaataa aatggaaaag 173520 ggcaacccaa tctctgtgac cttaaacttc cactgaaact tagagacggt tagcttagct 173580 ggtgagagcg tgctgctaat aacaccaagg tcgtggtttc tatcccatta cagggcagtc 173640 aagctcaagg gaaaaaccct gttctttggc acagcttcca tggcctgcta gccgtttaca 173700 gcgaggcaaa agagtagaga tgttttagtg aactaggcca tgacttgggg agtctccacc 173760 ttgaatctgg ttgtgggacc aaggaagaga atctgctgag gctgggtaga gagactctag 173820 agcaccttag gccacaggac agcagaggat gagaataaca gaactggctt cagaaagtag 173880 gtgtcagtcc aaggcactgt attcaataca tgtagcaaag aatgagcttc tgacaccagg 173940 aaagtcttca gatggcagtg actgcataaa ccggtgtcag gatgtctgac tataaaggat 174000 gggacacctt ccatcaggtg agagctctgg aggtggagtc tgttcctgga agaagcatgg 174060 gtaaatgtca tcaaaggttc cctcagccac cactgggttc agggctgagg tgcacctagg 174120 aaggcttggg cagaagcatg acccctggaa cttggccaac tgagccatca gagagtggtg 174180 caggtgagga gtggtagatg tgtagtgaac cactcagctg tctgcccagg ccttgggtgt 174240 ggaagtagag tcttctgtgt ctttgggcag actgaattat aagcttcacc agatcgccaa 174300 gctaggaatg ttgacatacc tggcttgggg tcagggaggg actgaactgt aggtgggggg 174360 ccccaacaaa tctaatcata agaatctatg agcgtggaga cagaaggacc aaagaaggga 174420 tgctgtaacc aattatcatt attgaaaaac taggcagaga ttacattcaa ttggcagtac 174480 cacccttttt atctctgaca tagttccaga aggatatact atgtatctag tgtgacactg 174540 tctgatagaa ttgtctgaaa tgatggaagt gttctgtggc tacccatttt gatagccact 174600 agccacaggt ggctattgag cacttgatat gttgttggtg tgactgagga actaaannnn 174660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 174720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnncttg agcacttgat atgttgttgg 174780 tgtgactgag gaataaattt ttaattcaat ttaaattaaa tttaatttaa atttaagtag 174840 caacatgtgg ctggtggtta ctggattgaa ccgaacagat ctagatacta gagtaagtgg 174900 tagcagcaaa tcctatattg gaacaatgta aattaacaat tataaatata tgagcaggcc 174960 aaagcccaaa tgggcctgta ctcttagttt tgctatatat tcaaccataa ctagcactca 175020 ttttttaaac ttataaaatg caaactcatt tggttgtgat gatgaatgct caggtaattg 175080 ttgagtttca acacagtgac agccaggaac tcattttgga gacttggatt gtgccacagt 175140 ttgtccctct ataaaatgat gatgaaaatt ttatcagtat ctgtctcaag ctgtagttaa 175200 tgggccaatt tctaaatatt cctgtcaaat tgtatagcca ttgttttcaa agtagttttg 175260 aaagtaggcc attggtaaag caatctatta aagtgcagga agaaagtaat agaatctctt 175320 actttttaaa gtctcattat gaaaattata tttcagtttg tatgccttcg atgtacataa 175380 tatattaata cacaaatata ttaatgcagc ggtccccaaa ctttttctca ccagggactg 175440 gtttcctgga cgacagtatt tccatggatt gcagcgggga tggtttcagg atgaaactga 175500 cccacctcag atcatcaggc attattaggt tctcataagg agcacacagc cttgagcagg 175560 tgcagttcac atatagggtt tgcgcaccta tgagaatcta atgctgccgc tgatctgaca 175620 ggaaatgggg ctcaggcagt aatgctcgct cactgctcac ctcctgctgt gtggcccagt 175680 tcctaacagg ccatgaactg gtaccagtct gtggcctggg ggctggggag tcctgcatta 175740 atgtaattaa atatgtacat ttcttgagag tgtttgttca aatatttttt cctaatagag 175800 acgtataact tagaaagtat ggaaccctct ggtcagtagc atattttatc aaaaaggcta 175860 tccgtcgtgc taaccaatgt gattaaatgt tcattttagt ctcagatatt ttgataacat 175920 aataataggg aagttatggt tattgcatgg cttttcttta ctgtattttc aataactata 175980 ttaatgggtt cagttgttac tagttttata attctgtttt attctcaatg agtcttcctg 176040 tttctcccca cgtctttcct atggttcatt tccctgcatc tttacagctc cctggaacat 176100 tctctcaaat caatcagagg cttcaaaact gggcagtctc attttgtaac ctgctctgac 176160 tcgcctctgg gaggcctccc tccccactca cagctgcctt cctgcatgat gtaaaatgaa 176220 tacagtgcca gaaagactga tccttggaac ctcttcctta cttagtttct ttatagttct 176280 gattttagaa atgaccattt tacttccagt gcccttcccc acaccagtta gctgagactc 176340 tatgcaggaa gttcccagtg atcagaactg ttcccatagc tcccaggtga ttctgacatg 176400 cacccggcat tgagcaccat ggacatggct gctgtttgtt atcctcgagc tcgcaaagca 176460 gtgtcggata ttgcttgatt gttgcacatt aatctactgc acggtccggt aggtagccac 176520 tagccacatg tggccattta gatgtaaatg aatttaaatt aaatagtatt ataagttcaa 176580 cacctcagtt gcactctctg tattcaagtg ctcagtagct acaagtggtt ggtggctacc 176640 attttgggca gtgctactat acaacatttc tatcaccaca gagagtgctg atgaataata 176700 gtactaacaa ctggaaacat tgaaatggag aggtgaagga gagaaggcag aatataagag 176760 aaacttcaaa gcattcagcg tgtctgatag gcgctgtatc ttacattatg tttggagcat 176820 agtttttgaa tttcttaatt ttcaaattcg gttgaaacag attttggtca attgaagtga 176880 aggactatgc ctgctttaat ttgcgtagct tacctttgtt tcacgtgtct cccttattac 176940 agtgtttgta gcagcatcta actcaatccc taacttcttt ttggtgcagg gaccatttaa 177000 aaacaatttg atcatagagg ttatctcctt tgcaatccat attgttttat ggaacaggtg 177060 aacagctggt gacaatagcc tcaaggtttc taatcccacc aaaggaaaat atggtgtcag 177120 taattacctt gtactatgat atttgtgaaa tccaagagag ggctagatct caggctctaa 177180 taatacatcc gtataaacat ctcagtaggg caccacggaa gagtcttagg atatcaggaa 177240 caataagagc gggagaatat cgaccttaat attctttaca cttattaaaa agtgaaaaga 177300 cagccataaa gcagaatgag ttcctgtcct ttgcagggac atggatgaag ccagaagcca 177360 tcattctcag caaactaaca caggaacaga aaaccaaaca cctcatgttc gcactcataa 177420 gtgggagttg aacaatgaga acacatggac acagggagtg gagcatcaca caacggggcc 177480 tgtcgggagt tgggggacta ggggagggag agcattagga caaataccta atgcatgtgg 177540 ggcttaaaac ctagatgacg ggttgatagg tgtagcaaac caccatggca catgtatacc 177600 tatgtaacaa acctgcacgt tctgcacata tatcccagaa ctaaaagtaa aataaatgaa 177660 aaagaaataa aaaataataa aataaaataa aataaatgaa aagtagccat tttaccagtt 177720 gagtatttac tgacttttgg tgaaaatcac tttctaagat tactagaaac cttatgaccc 177780 tcggcctcta ctcccaccac gtgcggattt tcacctccac ctactttgtc acgtcacatg 177840 cccttctgct ctttaggaca cttgtattgg gttcctcccc cacacgtaaa cagaacacac 177900 aggtctgtga atggacctca ttatgctcat ttgtctttgc caagaactat tgaaaatgat 177960 cacaaatgac tatgtaatta taattaagat tttgtacatg catacacttt atttttaaca 178020 agtttgtcct gttaaatgtc accccatttt gaatagtaac attcactggt gcaaggaaga 178080 attattaaaa tgacaattta actgatatcc ttgacaggta agccagttat tgtatttcat 178140 aattgtgatt attacaatac ctatgaagat taattaggac aatttattct ataggacttg 178200 gttatcaaaa tgatcttttt tcccatttta gtccatacat cttcagtttt aatttccttc 178260 ttccaaagaa ctctgagtct tgcccagtgt gatacttcag attttgtaaa aatataatga 178320 agaagaataa catgtatcag atcttttttt taatgtactg ggctaaaaat tataagcacc 178380 atcaaattac tagaaaattc ttttaacact ctgcttctta gttaaaaaat gattcctttt 178440 tgtgataatc ttataatttt caaagtatca ttttagaaat tttaaaaaat tattcttgtt 178500 ttcattcagt ccatttcatc agaacttaga ttttttcttc cctctacagt atgtggtctt 178560 gatgtgcttt ctccttgcaa aataaaatct ttagtttcag gatctctgtg ttctattcct 178620 tcaatttaaa atcataggaa aaataactat catttcctta tgtctgtctc caattccccc 178680 atcattttct gtgagccaat tttcttcttt ttcttctgtc tactgtaagg aactttttac 178740 tctgctctat tctctgcaat tcagggctca caatttcttt gacttctcag attatccttt 178800 gtacttgtgt ctactttttc attaaaaaaa aaaaggcttc ggtcttattt tgactttatc 178860 atctttatat tgccatattt aaaacccatc tgcttattga ttgaaccaaa cttttcatct 178920 tacttcatca tactgaatgt ataacttctg aatgacttaa aaatcatcac ataatgtgag 178980 agaattttct atcatattca ggtgactgca ttgtaagcaa tgaagttgaa gaaaaatagc 179040 ttataatgga tataatacca agaaataata agaatgagaa tctgcgtata tcatatactg 179100 ggttaacaag ctcacaaggc aaatcaccat tttattagat atttaacaaa tcatactagt 179160 actggaggaa gtatagcaga aaaaaggagt atggacattg ggattagctg ccttgctaat 179220 cttttgtcag tccctagtga catgcttttg ggttgagtca ttgttacctc cctgagctgt 179280 ttgtttataa aatgggggta aatatctcag atgtttcagt gttgtgacat ataaagcgtc 179340 ctccatagta cataataccg taagcactcc ataaggtaat tcttgtcctt ttaaaaagta 179400 tacacttttg agttcaggac acgtacactg taacctagtt gtaaccattt taataaaaga 179460 aggttttgat catttttgat aaatgtacta catgaatagt taacttgcct ttcacttcct 179520 ataccaacgg aaattttggt aacaaattta aagaaagcat taggttgaat atcccatctg 179580 attaaatgtc aactaaatat tgtttctggc ttttaaaata tttctaattc agttataaaa 179640 caggtctatt actcaggagg ctgaggcagg aaaattgctt gaaccaggga gtcggaggtt 179700 gcagtgagcc gagatcatgc cattgcactc cagcctggcg acagagtgag attccgtctc 179760 aaaaaaaaaa aaggtgaaat gaaaaacaaa aaagaggggt gaaatttctc tgcattctcc 179820 ctttctgctg ttgggaaagc cctttcatta ccaagaatgc atggaattct gcttattaat 179880 ttctccatct atgtgtctct gtgaaaaata ctaattattt acaattttgt aagctatgaa 179940 taaggtctat gttttctctg aaattatagc aacaggagca tttccccctt atttgggccg 180000 caatcttttc attctgattc ttaccataac ttctgacttc tgactttatc atgtcttctg 180060 atttctacta aacatgaaca gaatgaatga cttctagaaa tggatacagg tgtaatacat 180120 ataaggccag ggaaccactt aattatcttt acaaagtact aggacttcag aaaaatcaaa 180180 tgatgaaatg gagctagctt tagtatgttc tacttatcat tggactatta atcatgtctg 180240 tctgatgagt tacctaggac ttcaactgtt tttatagatt taaagaaaat attataaatg 180300 tatcttacct ggatttaaga ctggacagct gattttggat ttttttctgc taccctgttg 180360 ttgatatcac tgacatcagc ctttgcattt tgactggagg ctcctttctc tctttctctc 180420 tctctctctc tctctctata ggacaccagt agttatgtca ggttgctaag tattttccca 180480 ctgaaggaca aatattctgg agcagtatat atttagcatt tgacatttga taaacaagct 180540 tgtttgagat attttcaata caatttcagc tttggcaatt gtaagcaaag gatccagttg 180600 gtaattggtg aaatgaacag atgtggacac gctgcctgca tcgagatgca ttaatttttc 180660 tgaaaagtgg ataagatctt gtgagaatga ataatggaat tcaaatcaga tggggtgaga 180720 tatttgatat tcaggaacaa atcacagtat aatagatctg ctactttgtt tggttttaat 180780 ggggagttgc taatgctgaa atatagtcag agaaaaggaa cgtggaattt ctatagagga 180840 gagcctggct ctggggtaat actactgtcc ttggtggaat gttgtctttt ctgaagacat 180900 tggttcaatt caatacatga aacattcatc gattattatt tagaaaagct aatctactga 180960 caagacacag agttaagtag tgaaaataca gagacctaga cacagttctt attaagaaat 181020 tttttaattt aggtggcata tttcagagag aaattctctg cttggggcaa taggtacctc 181080 ctttggaata agcatggtga gaaagaattg cttctggcag attagtgaga agagtgagat 181140 attttctttc gatgacctct ctattaaaat ttgagtggta aaactttgtg atgattcagg 181200 ctcttcataa ttcttaattt tatcatcctc taataccagg acttgcccag atcaatattt 181260 taggaaacag tcatgcttgc taaacccagg gatttctatt aaccactaga taagacataa 181320 gtttgtcatg caacaagtat ttattgagtc cataatttgc ccagcactgg gctttggtac 181380 tctgggcctt gatactctag gttgtgtcag agatgtctaa tatatttaag gtgacagagt 181440 tcacaaatga gactttatga aaatgaatat ccctttttaa gtctcgagaa atatgatgtg 181500 cacccgcttg aggctttatt aaatctccag cgagcatgaa cttgtttgtg acccaattgt 181560 agaattgttg tatgatgact atcccactgg caggcacttc ttgtccaaga gaatgtaatt 181620 ggatgttggt gactcaagca atcctgggaa gactcctcca tgaccaaatt aaagacaaca 181680 ggggcttggt ttgtactcag ctctacacca atcagcatga gacaaagaag agatccatgg 181740 caaagtgggg agactactgt ttattttaca agctagagaa ggaaaactgc agttcctgag 181800 ttgcaaaact gctaagaaat gggagaacac agaactttac aggctgaacc ttggtgtctt 181860 agttattcct cttggctaca gaatgccaac cagtaggaga ttcatcactg agatattaca 181920 gggaaatgaa gccaggcaag aaaaatatgt attccctttc ttctcagccc ataaattttg 181980 ttattaataa atcagactct tatagaacag cttgccacgg ctgtctctag aaatgttttt 182040 attagcagaa tttttattaa aataaaatac acagtagttt taagagtgaa cattatagtt 182100 ttaggtcata aggggtgtca tggagaacac atgtggatgc tacttgccag ttacttgatc 182160 taggccttga ctcttggttt tctgttgctc ggataagtta gcatgatttg acatgcagtt 182220 aaaggtgtgg taacctgtga ttgatttccc attcttgatg ctccctgcct ggacttctcg 182280 gaaaatttca aaacaattca ttcttctatg agggctgcct ccttggttgc ttcggctaaa 182340 cagtgttgag caacaagttg ggaaaggaac gttgcagtaa cttttaaaaa ttaagttaga 182400 aacaaatgtc atcaaagtaa atgataattt gccaatatga ttgagcaaaa agatgaagat 182460 gcacgctccc tacgtatttg ctttgcagaa gaattaattt gaaaaataat aacatatttt 182520 aaaatgaatt gtaaatataa acacatgcta attgcagagg ggaatccctg tgattattca 182580 gcagtttgtg tttgtcaagt gcttttcagt cagtccattc cagctcagca gggcagaggc 182640 ttgggctgtt gtaaacttgt gggcagatac ccagtgatgg ggcagacatg agcaggtagg 182700 gctgacagca tgtgaattga gttttcttca gtcatgctgt tgcagctgct cccttccctc 182760 attgctgagt ttgccacagc aggtaggaac ctaactctgg agcctgggat gaaggagaac 182820 ccacattggg cttgaggaac aagatctgcc accctggtag gccctggtta aatctcatgc 182880 aagtgtagca atgagagagg gtatgattga gttctaattt aggaggaaag gggataatgt 182940 gccctttgca cccccaggag aaatcattgc tcatctgtgc ctaagtagac ttatcaaggg 183000 cagttggttc acaatggtgt atcaccccaa aggactatag tgttatgaga acttgccagt 183060 gtatttgaat ttgggtgctg gcagatgaca tcatgaggta ttatggttac ccataaatat 183120 gctagtttat tgagaaggtg gtagacatgc tagtggatga gagggaagga cagaagcagt 183180 tagtaaacag catctgcaac aattcagtta actggtggtt gtcacagtag catggtggaa 183240 aagttggcaa ttaataactt ctaagaaaac tgaactaatg aaccaatcct gcgtgtgcta 183300 tgtgtataac ctccttctca ctattaacag atttgttcca aacttatata agacaatgaa 183360 aataaagctt ggcaatatag ggaagggatg gagggataaa gctgtaaatc acgtcacagg 183420 caaattaaga tataccactg gatcaaggga tttaatgcag aaagactgat cctaacttat 183480 ttcttttatt tagcaataag atttgttact tacattgatt atttaaaatg agttgcatta 183540 ttagaaagga ctattttgaa gacaactata ataaaatgtc agtaactgat agtagccaag 183600 atattttaaa tatatcaaag ttgtgtcatt aatattaatg tgtcccttaa tatgaagtcc 183660 tgcccaggct tatttatgta ttcaacagac acatacctgt tgaagtgtaa cagatattct 183720 ggacacaagc aatggtaaac aagacagatg cagtccctgc tttcatgcaa tttgcaattg 183780 aatggtcttt gacattttat tgtgattgtt ttagttattt aattggagaa ggttttaatt 183840 taaatttgtg ttatattcag tgttaaggaa caaaaatgta atgtgcatct ctgagactca 183900 gtaacacttc tggttttcct ttttcattta aagaaaaatt tagtgcccaa gataagctag 183960 aatttttgga atcaagtaat tgatgacctg ggagccaatt ttattacaat agtgttttta 184020 gtggtcttag aacttttcag agcgtggtag ctctgaaaat aacactgtaa taaattcaca 184080 catacatcta tcatccaata aatgttaatt gaggcccact acagcattgt gttagattct 184140 gaggttacaa attgttgacc ccatgtcgaa catgttgacc ccatcaatgt aatcagtttg 184200 acattacaca gtcatttaaa cattaaagtg tcagcggata ttttagttgt aattttgata 184260 agtgctctga aggagaaaac agtgggtgtt gtgaaaagca gtatttggtt gattgattat 184320 tatagaggat ctgagaaaac ttacttgagg aaggaacatt tggctgaact caaagagatg 184380 agtaggagtt aagtaagcaa ggaagaaaag aagacacatg aaggaggaag aatgttctag 184440 aaacacacac acacaggtat atgtatatgt acatgtatat gtatatgcat atgtcttcct 184500 tagaaacata taaacagctg caacatgatt gaacttattt acccaattac caaagcttat 184560 tttgcaccat gaaggtggag ataaaggctt tttaagcagc aaggatagaa tctttgtagt 184620 ttttatttat aggctggttc ttctgacaac tttaattttt catctttacc aacttcatgg 184680 tcttcagtac atacaatgca atcattatta taaaattata ttttgactca aactctaagg 184740 taggatgatt cagctgtgcg ccatcaacat agcagcatga atggtagaga ctagtcattc 184800 caaacagtga aggggcaacg taaaactaat tttaatatta tatgaaagta cttcttgccc 184860 ttgactgctt tttttttttt ttgaagaaag caaactttaa aaatttattt tagatttaca 184920 gaattattgc aaggatagta agagagttct catatatgcc tcacccagtt tcctctatta 184980 tcgacatctt acattatatg gtacatctat cataactaat gaaccaatat tgtttcatta 185040 ttagtaacta aatctatact ttattcagat tttctaagtt ttcctctaat gttctttttc 185100 tgtcccagga ccccatcagg atatggtatg tatagttgtc atgtcttccc aggctcgcca 185160 tggttgtgac agtttctgag actttcattg tttttgatac cccaggtagt ttaggcattt 185220 tgtagaatgc ctcccagtct gaatttgtct gatgttttcc tcatggtttg actggcttta 185280 atgtgttttg gggaggaaga ccacagaggt taagtgtgat tgtcatcaca tcgtatcaag 185340 ggtacatgcc atcaatatga cttatcactg ttgatattaa ccttgatcat ctggcttgag 185400 atagtatttg tcaggtttct gtattataca gttactcttc tccctgtcca tacagtactt 185460 tttggaagaa gccattttgt gcagctcatt ttttttttaa ttttaatttt aagttctggg 185520 gtacatgtgc agcatgtgca tgtttgttac atagttaaac gtgtgccatg gtggtttgct 185580 gcacccgtca gctcatcacc taggcattaa agccaacatg cattagttgt ttttcctaat 185640 gctctccctc ccccaacccc aatctgacag gtcccagtgt gtgttgttcc cctccctgtg 185700 tccatgtgtt ctcattgttc agctcccact tctaagtgag aacatgtggt gtttgggtct 185760 ctgttcctgc attagtttgc tgaggataat ggcttccagc tccatccatg tctctgcaaa 185820 ggatttgata tccttccttt ttatggctgc atagtattcc atggggttta tgtaccacat 185880 tttctttatc cagtctatca ctgataggca tttggtttga ttccatgcct ttactattgt 185940 gaatagtgct gcagtgaaca tatgcataca tgtatctttg taatagagtg atttatattt 186000 cactgggtat atacccagta atgggattgc caggttgaat ggtatttcta gttctagatc 186060 tttgaggaat tgctacacca tcttcctcaa tggttgaact aattaattta cattccgacc 186120 aacagtgtaa aagtgttcct atttctttgg cacctcgcca gcatctgttt gttcttgggc 186180 ttttaatgat caccattctg actggtgtga gatggtatct catnnnnnnn nnnnnnnnnn 186240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 186300 nnnnnnnnnn nnnnnnnnnn nnngaattca tcaccagctg acttgccctg cagaatatgt 186360 taaaagatgt tcttcaagca agaggaaggt gatataagtc agaaacttgg atctacataa 186420 agcatggaag ataatcagag aatgcatgaa ttaaggtaaa ataaaaggaa atttatttta 186480 cacaggattc taaattcttt ctaaattctt aattgacgta aacaataact gcctgtttaa 186540 aatcataata gcagcaatgt ataggtgatt atagtatata ggtaagtgaa atgaaataaa 186600 tgacagctat gtcacaaggg acagtaagga ggaattgaga atactatgtt ataatatccc 186660 tatatttcat gtaaaaagga atagtgttat ttgaaggtgt atttagaata cttaaaaatg 186720 tatactgtga actttagcgg caccactaca aaaattcttt aaagaagtat agttaagccg 186780 ggtgcggtgg ctcactcctg taaacccagc actttgggag gcagaggccg gtggatcacc 186840 tgaggtcagg agtttaagac cccagcctga ccaacatgga gaaactccgt ctctactaaa 186900 aatacaaaat tagccgggca tggtggcaca tgcctgtaat tccagctatt cgggagactg 186960 aggcaggaga atcgcttgaa cccaggaggc agaggttgcg gtaagccaag atcgcaccat 187020 tgcactcccg cctgggcaac aagaggaaaa ctctgtctca aaaaaaaaaa aaagaagtat 187080 agttaatact ctaagagaaa agataaaatg gtatgacata cattgctcaa ataaaactac 187140 gaaagaccaa aaagaagcgt ttggcaacaa atatgaaata gttaataaac acaggtttat 187200 ttttattcaa atatatcaac acttgcttta aatataaatt gtttaaatat accagttaaa 187260 agatggaaat tgtcagattg aattttaaga aagaccaaac tatatgttgt ctacaaaaag 187320 ccccacttat tgatttattt attttgattc tcctgcctca gccccctgag tagctggctg 187380 cctccacacc cagctaattt atttttactt tttaattttt atttatttat tttttatttt 187440 actttaaatt ctggatacat gtgcagaatg tgcagttttg ttccataagt atacatgtgc 187500 catggtggtt tgctgcacct attaacctgt catctaggtt ttaagcccag catgcaaaat 187560 actttatttg gtatttatcc tagtaataat gcccacttta aatgtaataa ctctgatatg 187620 ttaaaagtaa aggaatggag aaagatacac catgctaaca ttcacaaaaa taaagctgga 187680 gtggctatat taatttcatg caaagcagac taccaaagaa ggaaaagtac caaggataaa 187740 gatgatgata aaggggtcag ttgttcaaga tgatacaaca atcataaata tgtgtatata 187800 tgtgtatacc taacaaaagt gaatcaaaac acatgaagca aaatgattga aactaaaagg 187860 ggaaatagac aagcccaaac cattattata cttagaaacc tcaccattcc gctgtcagta 187920 attgctagtg caagcaggca gaaaattaat acagatatag ttgacctaaa cggtatgatg 187980 aatcaacatg gtctaattaa tatttataga atactccatc aaaccacaac ttaatacaca 188040 ttcttctcaa gttctgatgg aatacgcacc aagatagacc acattctggg tcacaaaaca 188100 cccttaacaa atttaaaaga acagaaagtg tacaaagtag gctctcacac caaattggaa 188160 ataaattaga aatcaacaga aagatagctg gaaaatatcg aaatatttag agattgaaca 188220 acacactttt aaagaacgta tgagtcaaag aaaaagcctc aaaataaatg gtaaactatt 188280 ttgagctaaa tgaagataaa aatagaacat caaaatttgt gggatgcagg aaaagcagtg 188340 cttagagaaa aattcatagc attaagtaaa tatattagat aagaaaaata tataatatca 188400 ataaccaacc taagccacca cctaaggaaa ctagagaaga aaaaaactag ataagcttaa 188460 agcaagcaga agagaaagaa taatatagac agttcccaac ttaagatggt ttgatttatt 188520 attttttttg acttcacaat ggtgcaaaag taatatgcat gcattcagta gaaactgtat 188580 tttgaatttt caatttagat cttctgtgct agcaatatat ggaacaatac tctcacttaa 188640 tgctgggcag cagcagcaag ccgcagctct cagtcagcta tgtgatcatc ggggtaaacc 188700 atcaatactc tatagtgtgt tttgttgcca gatcattttg ctcaactgta ggctaatgta 188760 tgtgttctga gcacatttaa gggaggttag gctaagcgat aatgtttggt aggttagatg 188820 cattacataa gtcaaaagac ttatgatatt ttcaaattac agtggatgta ctgggacaca 188880 accccatcat aagtcaagga gcatctgaaa ttagagcaga tgccaataaa attgaaaaca 188940 gaaacatgat aaagaaactc agtgaaacaa aaactggtta ttttaaaaga gcaataaaat 189000 tgataaactt ctattcaggc taattaagaa aaagaagccg ggcacggtgg ctcacgcctg 189060 taatcctagc actttgggag gccgaggcag gcagagcact tgaggccagg agttcaagac 189120 caacctggcc agcatggtaa aacttcatct ctactaaaaa tacaaaaaaa aaaattagcc 189180 aagtgtattg gagcatgcct gtaataccag ctactcggga ggctgacaca tgagaatcac 189240 ttgaacccaa gaggcagagg ttgcagtgag cagagatcac accattgcac tccagcctgg 189300 gtggcagagt tagactctgg caaaaaaaaa agagagacag aaaacataaa ttaccaatat 189360 cataaatgaa agagaagtca ccacgactgg tctcttggag attaaaagga taataaagga 189420 atattatgaa caactctatg ctcacgaatt tgataatttg gatgaaatgg accaattcct 189480 tgaaatacac aaactaccaa aactcacaca tggagaaata aatagcctaa atatctctat 189540 atatattaaa tatattgatt caataactaa ttaccttcta aagaaatcat ctggctcagg 189600 tggtggcaag attacttcta acaaatcttc aagaaagaaa ttgtgccaat tctctacaat 189660 ctgtgttagt aaacaggcag agaaaacaca tcctaactca ttctgagtct agaattatcc 189720 taatacccaa atcagataaa gatattataa gaaagtaaaa ctagagacca atatctctcc 189780 tgagcactgg cacaaaatct caacaaaatg ttagcaagac agaacaaacg atgcataaaa 189840 taaattatac atcatgaaca aatgggattt attccatgtc tgatggcaaa ttcaacattt 189900 gaaaataaat caatataatc tgccacatta acagtgaaaa cgggaaaagt catatgatca 189960 tattaattga cacaggaaaa ctatttgaca aaattcaaca gctatttatg attaaaaact 190020 cagcaaattc agaatagaca gaaatttcct caatttcata taggaaattt aaaaaaacaa 190080 tagctaacat tattcttaat gacaaaaaac taaccacttt cccctgaaga tgaggataat 190140 tctaagatat cttatctcat tcctcctatt atacattatg ctagaaatac cagcaagtgc 190200 aataaggcaa aaaaagaaat aaaagatata tagattggga aggaagaaat aaaacatctt 190260 tattcacaga tggcatgatt atctatgcag aaaattccaa tgaatcaaca acaacaacaa 190320 aatctcccct ggaactaata agtaatgatg ccacggttaa aggatctaat gtcaatatac 190380 aaaagtcaat ttctttccta catatcatca tgaataacag gaattcaaag tttagaaaat 190440 accatttata atagtacatt caatactaag atataaatta acaaagtatg tacaaggcct 190500 atatgtaaaa atctataaaa caatgaaaaa tgaaagaaga tcttaaaatg atgaagagat 190560 aatagagatt gaaagttcaa tattattaca tgttcatatt attcaatatt gataaaatgt 190620 caattcttcc caacttaatt aacagattca gagtaatcta aatccaaatc ccaataatct 190680 attttgtaga tattgacaat tgattccaac atgtttaaag aagggcaaaa gacctagaat 190740 agcctttaat actgaagaag aacaaaattc tgaagaaggt ggagcacttg cactatttca 190800 tttcaagact taccataaag gctacagtaa taaaggcagt atggtactgg ttaaagtata 190860 aacagatgga ctagtgaaac agagtaagaa gtccagaaat agatccacac aaataaggtc 190920 aactgatctt tgacaaagaa gagccaatta aatgagaaaa aggtcatctt ttcagaaaat 190980 attgcgctga ttacccttaa gatatatata aaaagaaaat gttgctgaag caactggaca 191040 ttgatgtgga aaaagaaaaa cttatacaca aaccttacac cttaaacaaa acttaaggtg 191100 aatcattgat ctaaacatat aatgcaaaat tataaaacta cttcttgaag aaaacagaaa 191160 aaattctata tgatattgaa tttggtagta agtttttata tacaacacca atagcacaat 191220 atggaagaaa aaaattaata aattgggctt cattaaaatt taaatttcta ctttgaaaaa 191280 aacaattaag agagtgaaaa gataagccac aaactgggag aaattatttg tgaaacacat 191340 ggctgataaa agacttgtaa tcaaaatata caaaaaaact cctcaaactc aacaaaaaga 191400 aaacaaaaac ccaattttat gtatgtacgt atgtatgtat gtatgtattt tgagatggag 191460 tttcattctt gttgcccaga ctggagtgca atggttcagt ctcagctgac tgcaacctcc 191520 acctcctggg ttccagtgat tctcctgcct cagcctccca agtagctggg attacaagtg 191580 cccgacacca tgtccgacta atttttgtat ttttagtaga gacagggttt caccatgttg 191640 gccagaatgg tctcgaactc ctgacctcag gtgatctgcc tgcctcagct tcccaaagtg 191700 ctgggattac aggcgtgagc cactgcgccc agcccaaaac cccactttta aaatgggcaa 191760 aagatctgat gtacacctca ttgaaaaata catacagttg gcaacaaatg aaaaaatgct 191820 acatatcact aatcattaga gaaatgtaaa ttaaagccat gatgagatat catctcacac 191880 cagtcagaat ggctattatt aaatactaaa aaaacaaaca aacaaacaaa aaaaaccaga 191940 tgctggggag gttatggaga aaagggaaga cttatacact gctggtggga gtgtaaatta 192000 gttcacccat tgtggaaagc agtgtggaaa tccctcaaag acctaaaagg agaattacca 192060 ttcaacccag caatcccatt cctgggtata tgcccagtgg aatataaatt gttctaccat 192120 aaagacacat gcacatgtag gttcattgca acaccattca caatagcaaa aacatggaat 192180 caacctaaat gcccatcaat ggtatgcagg gtttaaaaaa aaacaatgta gtacatagac 192240 accgtggaat actattcagc cattaaaata aaaagaaaga aaaaaaacac gagagcatgt 192300 cctgtacagg aacaaggatg gagctggagg acattatcct tagcaaacta atgcaggagt 192360 ggaaaaccaa atactgcatg ttctcacttt taagtgagag ataaataatg agaaccaatg 192420 ggcataaaga ggggaacaag agacactggg gcctacgtga gggaacagag tgggagtggg 192480 gagaggatca ggaaaaagaa ctatcaagaa ctatgcttag tacctgggtg acgagatgat 192540 ctgtacacca aacccctgtg acacaaattt gcctgtatta acaaatgtac atatgtaccc 192600 caaatctaaa ataaaagtta caaaataaaa taaaaataaa aattaattaa aaaaaataca 192660 gttggcaaaa aaagtatgtg aaaatatcct caatattttt tgtcattaag aaattgcagg 192720 ccggacgccg tggcttatgt ctgtaatccc agcactttgg gaggccaggg cgggtggatc 192780 acaaggtcag gagttcaaga ccagcctggc caatatggtg aaaccccatc tctactaaaa 192840 atacaacaat tagccgggta tggtggcagg cgcctgtaat cccaggtact tgggagcttg 192900 aggcagagaa ttgcttgaac ccaggaggca gaggttgcaa tgagcgaaga tcgtgccact 192960 gcactccagc ctgggcgaca gagcgagact ccatctcaaa aaagaaaaag aaattgcaaa 193020 ttaaaacaat caaacactac tacacatcta ttacaatagt taaaatccaa aacactgaca 193080 aaaatcaaat gctgacaagg atgtcgagca tcaagaactc tcattcattg ctggtgggaa 193140 tgcaaaatgg tacagctatt ttggaagata ggttggcaat ttcttatgaa gctaaacaca 193200 ttattaccac aatgatgcag aaattgaatt cctagatatt tacccaacta atttgaaaat 193260 acacatgcac acaaaaacct gcacaaaaat gtttagagca gtttcattca taattgccat 193320 gaatttagaa gcaatcaaga gattcttcac cagtgagtgg ataaataaaa gtattattca 193380 gtgattaaaa agaaatgagc tatcagacca tgaaaatata tagatgaaac ttacatgaat 193440 attgctaagt gaaagtagcc agtctgaaaa agctacatat tgtatgattt caattatatg 193500 atattctaga agagacaaaa gaaagatatt aaacagacca ggggttgtca ggagttcaag 193560 gtgggaagga ggggttgaat tagagaaaca caggatattt tatagagtag agaaactatt 193620 ctatgctaca gcgatagaaa ctattctatt ccataggaac tatattacta taatggtgat 193680 acaatacatt aaatacttgt caaaatccat aaagctttac agaacaaaga atagaccaca 193740 atgtatccaa acttaaaaag ttaatttagg atgtcagggg aaactgggat ggaatgcaca 193800 atattacaaa agaatttaaa tgtatgacaa atacatgaag caaactcact aatggactta 193860 ggaaaataag gcgctaacct aagtgactcg gaaaatgagt aagtggaatc tgttagaata 193920 aaggcaaagg aactgtatat aaacactata ctctagttga taaagttgtt tcgtacatga 193980 gtacagatta acaattctga aacttccata gaagtatagt ggaattaaat aattaagtaa 194040 ataaatagca gatggtagga gccaggtttc tcactattgg tataggaagt gacagataag 194100 taagaggaga aggctagaat gttccatgct gttgcaggtt agaattggag acatcagtag 194160 gtactcaggt ttagcctaag atagatacag atggttacaa atagaaatat ttttatatgt 194220 gtgtagatat ataggttggt acacacacat atatctcttt gcactatcag cttagaggat 194280 ctagaagtaa caacacacaa taacaacaag tacaccaaca gcccatatct tggttttcat 194340 tgaaggaaat tattgctcct tggagaagtg gctgatcata gaactggggc aaaaaataca 194400 gaagataagt ctgaactatc ttgtagtgac agaaagtaag aaaaggcttt taaaaaaccc 194460 tacaatgata tgtaagaagc caaagagata caggagccaa ctgaaaaatc tccaaatggc 194520 caaagctgga acaagatgag ctacaaaata aaatagtatt ggactgtacc caaagcataa 194580 atattcatgg gttctagatg gctgatacta attgttgact aaataaatta atggaggaga 194640 atagacactt ccaaataatt tatagagcta ctccaccctt aaagaggtag agcatatctt 194700 ctcactcctt aaatatgagc tccacttaag tctttaatcc atcttgaatt aatttttgta 194760 taaggtgtaa ggaaggggtc cagtttcaat tttctgtatg tggctagcca gttctcccag 194820 caccatttat taaataggca atcctttccc cattgcttgt tttggtcatg tttctcgaag 194880 gtcaaatcgt tgtagatgtg tggtcttatt tctgagttct ctactctgtt ccattagtct 194940 atgtgtctgc atctgtacca gtaccacgct gtattggtta tggaagtact gtagcatagc 195000 ttgaagtctc gcacacgcaa atccatgcaa tcaagataca ggcacaggcc aagcattcca 195060 tcccaacacg agccgccgca cttgcgagac gcagctataa tggccgctgg ggatcagggt 195120 acgcgcatag atctacgggt acaggcacaa tggccaacat gcgcactcag gctggacaac 195180 gcgtagacca ggggggaatt cggattggct tgcccggcgg gcggacaatg ccttgtgatg 195240 gnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 195300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn ncacagaata cctaaagtca 195360 agccggcttg gtgggctggg tggtgacgaa gttcagtcct tcagttcaca aattagtcca 195420 tgactgacta cctggagaac tctgagcaag ctacctgaca tttctagatc tctctttcct 195480 cctcgctaat ctagaggaaa tcatggaacc caccacatcc aacgattcta agaattgaat 195540 gtgagaatgc aggttaggag tttaccatag ttccccggat atagaaaaca ctcaaaagat 195600 gttcgttgtt gttaccgtta ttttatgatg aaccctcttt cttttctctc ttgttgattg 195660 actctctctc cctcaaatgc tccttactca ttggctttga tcacatgcga gactgtccca 195720 taaaagagtc tcccttgccc cacatgctct ctaacttcca tcttctatct tatcccttgt 195780 tcccagctga actcagaaac gtctgcacat gaaatctcct tttcttcacc tctcttgcat 195840 tgctcaaccc acaccaatct gttttccacc ttagttaccc caaaaaagca acttccctag 195900 gattaccaat gaatcgcgtt gccaaatttt acaggtattt ttcagtccac atcctacata 195960 acctatctga agcagcttac aatgttgata cctcccttcc cgctgtgaga caggcttttt 196020 cccttggctt ccataatccc aaacacccca gttccttctg cctctcaggc tgcagcctcc 196080 cggtattgtt tacagattca atttcctcca tccaacatta agccagaggt gctcagggct 196140 caatcctagg tcttcttctt ctcttactac tccatattct cccacaagac aatctagtgc 196200 atgtccatgg cttccatcat caccaaatgc agatcactca gaatgtacgc tcccaacaca 196260 accctcttct ctgagctcct ggtacatatg tccagctgcc cacaggaagt ttctgctcta 196320 agatttagaa gtcacctcca tccctttatc cctcaaaata aatctggttt atagggagca 196380 gaatattaaa attcacaaac taataaatat tggcatgttt ttataaagtc tgtctgcata 196440 agtctaaatt cttacatatc ttggggaaat gtcctgaatt tagactaagg aagttatgta 196500 tactattgta aaacatggtt ctcattctcc caccccaaaa ctgaatatat atttcacacc 196560 ctagttcaga ttctctgctt aagtctctat ttttttccat ttactaaggg caagatgcaa 196620 catgcagtga aatgttttaa ctacagagct ctttgttctt tattcaactt aagggtcagg 196680 cccaattaga agagggtgga gtgaggactt gacaagaaat gctggcctca taaaacttgg 196740 ctttccatct ttaaatatac attataaaag tcactgtata cacgggcttc agatcaaatt 196800 aacatttgca ctcttctatt gcataacaga aaccagcaaa ctagtcagca gagttataaa 196860 cctgtaactt cagtaaaaga ccacacacgg attcagatat ccagacacag ttattatttt 196920 tagaattgtc cttattaata gggtcaaact gaagaagtaa tagaaccaga aacaaaactt 196980 atctgtgcag atgctaactg caagcaaaaa gtgtattctt ctgataccct aaagaaactt 197040 tcagtgttta gtctcctgtg gtatttatgc agtatatgct gatatatttc agcttttaac 197100 aaaaaatgag tatatggcca ggtgtggcag ctcatgccta taattccagt acttcaggaa 197160 gctgaggtgg gaggatagtt tgagaccagg agttttagac cagcctgggc aacataacaa 197220 tatcttgtct ctacaaaaaa aaaaaattaa atattagcct ggcatgatgg cacatgcctg 197280 taatcctagc tactcgggag gctgagacag gagaatcgct tgagcccagg aggtcaaggc 197340 tgcagtgagc tgtgatagca ccactgcact ccagcatgga caacagagcg agaccctatc 197400 tctaaaaaaa aaagaataaa ataaaaaatt aattagtata cattaagttt cagaagaaaa 197460 tagtcaataa ccattcaaac caaatattac tttgactcac tttctcccca gagccagtta 197520 ctttgtaagc cagaagaaga caggagaact gaattgggtc agagaccagt tggctgagtc 197580 tcatgtttgc actggccatc cactgtagat atgtatcttt gtagaaccaa gtgaaattcc 197640 tgaactaaca tgtttaatga ataaaaggta ctagattttt acaattgaat tcgtctctta 197700 acaaaaatgg aaatagatgt acaacagaat catgttcata cggcaaacct tttgtgacaa 197760 agctagaatt gataaactga caaaaagaaa agtttaataa atacatattt gatatatgca 197820 attaaaacaa attcttatta accaaacact attaacaact atttctaagt cttcagctca 197880 cgtcagaaga agaaaaacaa caaagtagtt ttttttcctt aatgagtgta acttggtcaa 197940 tatgtgttat taaagcaatt gatttaagtt gcattaagat agcatcggga gatataccta 198000 atgctagatg acgagttagt gggtgcagct caccagcatg gcacatgtat acatatgtaa 198060 ctaacctgca caatgtgcac atgtacccta aaacttaaag tataataaaa aaaaaagaag 198120 aaattctttt taaattttat tatctggtct tctcaagata atgcttgaga aaatcttact 198180 gaagtagagt tgattttcta aaaaacaact cacaccagtt gtcttagtga aacatagcag 198240 tgtgtgtgtg tgtgtttttt tttaactgaa aagacaggac tcgatgtatg tgaccagact 198300 ggcccgaaaa gtccttctgt gcaggcccgg atgaaccaag cccataggcg caaagccacg 198360 atgtgatgtt caggtgaagg tttggaaaaa taatccgcac tattttcttg cccatcaaaa 198420 gataaaaata aaaagcctct ggaggaatct aaggtttgac tggcaggaag tggaggggac 198480 aggaggtgaa tgagatggaa ccagaaagac aggaagcggg gagagaaaac gcctctcagt 198540 aggaatcacc gggcccaccc cagcccctgc agcaacagaa ggacccacat tcagcttttc 198600 cccaagcttc ccttgttctt tttccttctc ttctgatttt ccctcctttg gtagcagctg 198660 gtttggcttt gttgtcatta cacagaaagt ctgcatttgt tagttgtgaa aataaataat 198720 ggcccgtaca tatgcagaga ttcaaaagga atataaagac aggccaagca gttgcctgag 198780 agaaagccaa tataatattg caggtctctc cttttgtcac ctcttttccg tcagtatttt 198840 ctggtggtca cttcagatca aatctctttc ctgagtttcc tgaatgtcca cctgcccctg 198900 tccatcaaga cttgactctc tcacactcgt caagatggat gtgccccaga cagaactgac 198960 gactgtcttc tttcctcgcc agtctgttcc tattcacttc ccagctgaac caagaaatgt 199020 ctgcacgtga agcctgaaac atgggcatta ttctagattc aatctccttc ctcacttgac 199080 cctccctccc cacctcccac cacaggcaca cagatcaaaa caaatatttt ctaattattt 199140 ttcaaagcga aaccaatttt gcgctgggca ccaccatacc ttctccagcc cagatcatta 199200 ccacagccca ccgcaggacc ctttgcctcc agccttcccc cgccaatcct tccccacagg 199260 tggccacagt gatttttcct aaaatcatac gccatcaggc cactatcctg cctcaatgtc 199320 ctgaggctcc tccaagctct aaaaatgaca tctaaatgca atgccttcac agtttgcaaa 199380 gctcttatgt ttttccttgc cttctctccc cgctctaact cccatccaag ctctgatcat 199440 gtctttctgt tgacacatgc catgcttctc acccccagga cttggcacat gctcttcttc 199500 ttcatggaaa cacacttttt ctcctcttgg cccaactgac tcctactcat cttctaagtg 199560 tgccagtcaa gatgtcagtt cctctgtgaa atcttatctg cccttccagc catgcttagt 199620 ttgtgtctca tcataggact tactatgttg ggttttaact gcttgtctca atgcccagat 199680 cagtttaggc atggcaaggg atgggccata tctgtctcat ttatggctat tgatcctgag 199740 cccagcgcat tctcacacac atagtggagc tcaacaagta tccaatatct gaacaatact 199800 gagatgctaa agctcccctc acccccaact tcatttgtgg agcgcaggcc tcctgagggg 199860 gatgactggg gttctataaa ggaagtaatg agtgggaagg tgaggaccct gaacaatatg 199920 atggccattc tacctcagga ccccaaaact caaatccaca agaacaaggc ttggttctaa 199980 gcaggggcag tctgctcttc agcactgggt gaggccagac atgaacataa agcagatgtt 200040 catagatgaa gagggccagg aagggatcca tgaagccacg cattgctcat gaattatcct 200100 cactactctt tccgttttga ggccttgcct ctttcctaat atgactgtat ttcatgattg 200160 ccccaaagaa aaatcaacat attcaaatta ttccaaagct tgttttatat agaaatgttt 200220 ttctgaatta aaatgccatt ttcccctgct ataatacgtt ggttatggag acattttaat 200280 atggttcatt ttactaataa tgatttgttt tcatagtgtg ttttaacttt ttaaaatttc 200340 tattccaaga ttttactaaa ctctacaaga ttagcagttt ccttgaatca tctccccatt 200400 caccaccatc accaggaaac actttagctt taaataaaat aggtctatgg tattattttc 200460 ctagaaataa aaatccttat aaatgaagta ttaacaaggc tgaagaaaag gcatatcttg 200520 atcaaagggt ttcttacata taaactacat aaactgtcat gtaactgact gattttatga 200580 gaagctgaag ttcagagtac tcgtctcctg gcttaacagt tgaatattaa gatactacaa 200640 atatttgctt ccatcatagc ctacaaattt gaagatcaat ttgtcccaat aatgcaattc 200700 tgtgccataa gtatgtggtg tagttatttt tcctttatca taacttccta actttatgga 200760 gtcagaaatc gtacttgaat ggttctttcc tgctatttcc atcttgaatt ggcacatttc 200820 aaagtgctcc acaaactaca acacatctag ggatttaatt tgtgactaga aaacttcaaa 200880 atatatcaca tctattcttg ctttataatt ttttaaataa atgcattccc taaagagata 200940 tacagtactc tgaaaaaaaa ttaaagtcaa ggagactttc ataaggttag attaaaaggc 201000 aagttatgta aaccgggaaa aggtgtcgtc ccattaagga ataaacactt agcattcctt 201060 atcaacatat acaaacattt agctaactgt tcatatttta aggctcagaa ataaaaatga 201120 attctaaaag aaaaatgaat tctccaatgt ttaagcactc acacatcaaa taagagccaa 201180 ttttagctaa tcctgcgaaa aagcctcatt ggaggagtcc gacaaaataa tattttattt 201240 tcgaagtcct attttttata cccgattgac ccataaatgt agctaacata tataaagctt 201300 ggctaccttt acagtctcct tattaaaggc actcatcgaa tatttacata aaattaacta 201360 tggtttatca cattttgaag catccaggaa ctataaataa tttaagttga caagtaagat 201420 gtcaaaatct gacttccttt ctacttctaa gcatcagtat gttttcatag agtgttaaat 201480 acagctttaa atctgatgtg aaatcacaag tttctataca tatttggcca aaggaaaacc 201540 tatgacattt tagttttatc agtgaaagac tatattatcc tttaggtgtt aaggtacaga 201600 caacatagtt ttgagctgta acatttggga aaatagtaag aatctgcacg tgaattttca 201660 aagcactgtt atataaacca gcaactgccc aggcctgagt agacgcttcc aagagccgtt 201720 cctgctctgg cttgttcatt tcacacttgt gctcacttcc tatctggggg taattccata 201780 agcttgtcta gccaaatatt ctctctacca aggaaaccga gtcttctagg tactgaacat 201840 cacatgccag gaagtgtgtt atacattgat tgtttcattt aaccccctag gaactttatg 201900 aggaaggaat tatattaatc ctattataca gatgcaaaat tataattgaa gtttaaaagc 201960 ctgatttaag ccacacagca agcaagtggc agatgggttt tgaaccaagg tctcctttca 202020 ttccagaagc tgaactctta tgcattctaa caacctccat atatggaaag cccagcttct 202080 ccaaagggca agctcttcat tcaagaatgg tatctacttt ccagattgca atcatgcaag 202140 gaatctctgc aactgtctga ccaccaagtg ttccgcttct taggaagctc atgtatagga 202200 aagaaaaagt gaggaattaa cacagccaac ccaatgttac tgtcttctat ttaacatatc 202260 tacgagacaa atacttacta agaccacacc aaaattaagt tatttgggca atactttgac 202320 ttatatgaca aggatgaaat gcacagtcca actccccagc cacaacggta caagggaaca 202380 gaagtcttgt cctgccttac actctgagaa agatattgac tttctgcagt acctagtgtc 202440 tgtatctacc ccagcccttg actcctgagt gatgctttgt cttggtagga ccacccacat 202500 tatctactgt aaccaaagca aagagggagt atgggaatag cagcatagaa ttagaaaaca 202560 ggttcaaaca atgatatcat tggaactcac taaaagcaaa aagaaaagga agactggcaa 202620 agaatttgtt atagaaagaa gaattcaaaa tgtttttaca caaaagtggg aatgtatgat 202680 tgtcataaaa catgaaggat tangagtatt cacagttatg ccaaggaaaa aaaatcatac 202740 caaaacatct actaatcatc tttgagtagc nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 202800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 202860 nnnnnnnnnn tgtcagggag tggggggcta gggaagggat agcattagaa gaaataccta 202920 atttagatga caggttgatg ggtgcagcaa accaccatgg cacgtgtata cctacgtaac 202980 taacctgcac atgtatcccc aaacgtaaag tataataagc aaaaaaaaag aaataactac 203040 tagtctactt tcttagctta aataacaatt tctcctaaca aataaaaata aatgaatgaa 203100 taaaaccttt acaggatggt tgtttaatag aacaaataca atctatgcat aagaagaaat 203160 gttctatatt tatttgcatg gtaaatttaa ctcaaactag cgtagatgat ctggagcatt 203220 tcatagttct tatggttggg cacagcttct tcgttatttg ctgctttggc cctgcactca 203280 gacaaagaac tgtgtgaata ttagacattc agtaaacaaa agcaggagtg gttttaaggt 203340 ctacaccacc tgggcaccca cacagctcaa gtcgcaatgg tcatactgcg ctggcaggag 203400 agttatctca gataggatgc gccccacatc agaaagcaga gttctcattt ctcaagggtg 203460 tttggcttct caagctgcat tccatccaca tcccattcta gctgatgaga aaagagagcc 203520 cggaaaaatc tagcatctcc gtttcctccc ctctccagag ctagcctcag gaaagaaaac 203580 aatccagctg tgtggcctaa acatgctact taacatccac aggccacacc caggtcctca 203640 tcggtgaaag gaaagagatg tatctgttgt tcgttagtgc ccattcagtt ctaaacttca 203700 attattctct tttctcactc acctgaggtc tatgtctcct tgtcgtctgg cttcttgatg 203760 tcccagattg gtgatctttt tactgctttc aaagagttta cctaaatgtt gtagcagctg 203820 cactaaattg caggaatatg ggcctgttta gggaatgtta gctgtttgag tcccaagctc 203880 catgcgatcc tgggtgaagc ccgggttacc cttctgggat tcttgatatg tccgttgatg 203940 actgctatac aacccaatga aacaatatat gcaaaccctt tgtcaactgc aaaactttgt 204000 gccaataaaa ggtattatta ctccatacta tggactaata tacagccatt aaaaatgaat 204060 gagtgagacc aatatgtact tatatggaaa gatctccaat acacattatt cgatgagaaa 204120 agctaggcac agaataatgt gtagagcata aggtaatgta tgttaacaaa atatctatgt 204180 gtggggtgtg tgtgtgtgta catatgtaat tttcagaaga aattgttaat agtgtttacc 204240 tattgagaaa gggactgtag attttttaaa tattttttat tatactttaa gttctagggt 204300 acatgtgcac aatgtgcagg tttgttacat atgtatacat gtgccatgtt ggtgtgctgc 204360 acccattaac tcatcattta cattagttat atctcctaat gctatccctc ccccctcccc 204420 ccaccccaca acaggcccca gtgtgtaatg ttccccaccc tgtgtccaag tgttcttatt 204480 gttcaattcc cacctatgag tgagaacatg cagtgtttgg ttttttgtcc ttgcaatagt 204540 ttgctgagaa tgatggtttc cagcttcatc catgtcccta caaagtatat gaactcatcc 204600 ttttttatgg ctgcatagta ttccatggtg tatatgtgcc acattttctt aatctagcct 204660 attgttgttg gatatttagg ttggttccaa gtctttgcta ttgtgaatag tgccgcaata 204720 aacatacgtg tgcatgtgtc tttatagcag catgatttat aatcctttgg gtatataccc 204780 agtaatggga tggctgggtc aaatggtatt tctagttgta gatccctgag gaatcgccac 204840 actgtcttcc acaatggttg aaccagttta cagtcccacc aacagtgtaa aagtgttcct 204900 atttctccac atcctctcca gcacctgtcg tttcctgact ttctaatgat caccattcta 204960 actggtgtga gatggtatct cattgtggtt ttgatttgca tttctctgat ggccaatgat 205020 gatgagcatt ttttcatgtg tctgttggct gcataaatgt cttcttttga gaagtgtctg 205080 ttcatatcct tcacccactt gttgatgggg ttcctttttt cttgtaaatt tgtttgagtt 205140 ctttgtagat tctggatatt agccctttgt cagatgagta gattgcaaaa attttctccc 205200 attctgtagg ttgcctgttc agtctgatgg tagtttcttt tgctgtgttt tcagtcttca 205260 gataccccag caaagaacag aagctcttta gtttaattag atcccatttg tcaattttgg 205320 cttttgttgc cattgctttt ggtgttttag acatgaagtc cttgcccatg cctatgtcct 205380 gaatggtatt gcctaggttt tcttctaggg tttttatggt tttagttcta acatttaagt 205440 ctttaatcca tcttgaatta atttttgtat aaggtgtaag gaagtgatcc agtttcagct 205500 ttctacatat ggctagccag ttttcccagc actatttatt aaatagggaa tcctttcccc 205560 atttcttgtt tttgtcacgt ttgtcaaaga tcagatggtt gtagatgtgt ggtattattt 205620 ctgagggctc tgttctgttc cattggtcta tatctctgtt ttggtaccag taccatccta 205680 ttcaacatag tgttggaagt tctggacagg gcaattaggc aggagaaaga aataaagagt 205740 attcaattag caaaagagga agtcaaattg tccctgtttg cagatgacat gattgtatat 205800 ctagaaaact ccatcgtctc agcccaaaat ctccttaagc tgataagcaa cttcagcaaa 205860 gtctcaggat acaaaatcaa tgtgcaaaaa tcataagcat tctatacacc aataacagac 205920 aaacagagag ccaaatcatg agtgaagtcc cattcacaat tgcttcaatg agaataaaat 205980 acctaggaat ccaccttaca agggatgtga aggacctctt caaggagaac cacaaaacca 206040 ctgctcaatg aaataaaaga ggacacagac aaatggaaga acattccacg ctcatggata 206100 ggaagaatca atatcgtgaa aatggccata ctgcccaagg taatttatag attcaatgcc 206160 atccccatca agctaccaat gactttcttc acagaattgg aaaaaactac tttcaagttc 206220 atatggaacc aaaaaagagc ctgcannnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 206280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 206340 nnnnncattt atttatttat ttagagacgc cgtctctcnt ctcgttgccc acggttggag 206400 tgcagtggtg cgatcttggc tcattgcaac ctctgcctcc caggttcaag cgattctcct 206460 gcctcagcct ccagagtagc tgggaccaca ggcatgggcc accacaccca actaattttt 206520 gtatttttgg tggagacggg gtttcactgt gttgggcaca ctagtctcta actcctgacc 206580 tcaagtggtc ctcctgcctt ggcctcccaa agtgctggga ttacaggcgt gagccactgt 206640 gcctggctcg ttttaaaata atttaaaagt atattttgcc accactatta accagttaag 206700 ccatgatggt atattataat caccatggag atggtttttc tctttatttt attttgtttg 206760 ttttctgatt gctagcatgc tgattactct tcctattcta caagtgcctg caggcacgcc 206820 ccatttttgc tctcttcact tcatttttca tttctccctg tttcactctt catagcacat 206880 ttgtactctg tccacaccta gagacctccc tgttgaagtt cttcacattc tcttccctag 206940 agagggttaa cttgttgagc tcagagactt aaacttaaaa taaaatgtaa cagatatgta 207000 ttgaatgact attttatttt agctctagga gaaatgcaaa gatatatcat ccatagaccc 207060 tgaaatccag ctaagggttc tgcttataca caaggtgaaa ggttgtgata atgcacatta 207120 aacaatagaa gagttaaatt cagcactata agtgatgcct caaagcagca taatgggaaa 207180 aaggggtatt tcagaaaaaa atggtatgag ttcagaggca agagaaaaca gaatgctcta 207240 gattaaactc aaagacttta tggaggaggt ggtgtttcaa tagatacctt tccacagaac 207300 catgaagaga gttctactta attgtaagtg gcctgtgatt tgtcgttagt cattgcatgc 207360 tcaattctgc atgtgtgata actgtgtatt tttatggcaa aatcgcaatt acttttgcac 207420 caacctaata gaatagtgtg ggtttaaaaa aactatttgt aatatattcg aacatatttc 207480 ttatatatat gtttcaccat cattagcagt aaatctattt tgcatccaga gattgaataa 207540 tattttgttt ctaggatgtg agtgatgtac tattttaact tacttttgaa gtttgacatg 207600 ggagtgatat taataaaatc taaagatgct cctaaagagg agcaatagat aatgtaggta 207660 tagataatgt agctattatg gaggtaagtg tatttgatac tttttattat gatatgaagg 207720 gaaacaacta gtcccaagct acaatttatt aaggtaggct tagcttatac gccataattt 207780 ttatgtttgc aactttcttg attttcttcc tctggcttta cttctatggg atatttatga 207840 aaggatgttt ttaaaaatgg ctagagactt ttgcttctaa gagttgacat aaacttttcc 207900 acaacatgaa caattagtag atgatacact tagatacact cttgaatttt taaaattgtg 207960 gcagtaaaac tgatctcaga gaaggaagaa aatgctttgg ccagctttta tcaattatat 208020 acaacgtgtt tggaagattc agttcctctc gccttctttc tccctatata atactttttc 208080 ttaaggttgg tactattgat gcacttggtg taaacacatg agataatagc aaaatatgaa 208140 tctaggtccc agaaatgggc ttctttcact ctgccacctg ttctgactgc atttctcctg 208200 actttctgta aatcccgggg aggagctgga agagcaaggt gtgtgctagc ataactttgg 208260 ggatgaagta cccttctttt tttctgattt tgttcccaca tctccttact ggaccaagta 208320 agggcatcag tgtcaaactt cctgattgaa gatacatttt tgccctacca tgaagggctc 208380 tgggtaacat ttattgctta taaaatgctt ttttggtggc tactttgttt ctgaatataa 208440 ggcaagataa aaagtttgat tcaagagttt cttgtaaaca ctttgtgtgt gcgtgtgtat 208500 tcatatatgg ctgcacacgt acataagtcc atacataagt acagtccacc ctccatgttt 208560 gtgggttcaa catccatgga ttcaaccgac tgcaaatcaa aactatttgg aaaaaaatgg 208620 atggtagtgt ctgtgctgaa cacatacaga gattttcctt gtcattattc cctaagcaat 208680 ataacaactg tttacagaga atgtacattg tattaggtat tataaataat ctagagatgt 208740 tttaagctat atgggatgat gtgcgtaggt tatatgcaaa tattatgtca ttttatataa 208800 gggacttaaa catctataga ttttggtgtc tgaggagtct tcgaacaaat cccccacaga 208860 tcctgagggg ccactgtata tatatatctt cataaacaca cccacacaca caaacacacc 208920 cacccaccca cacacacaca cacaccaatg tgtatatact tttttttctt ttttttaatt 208980 cgagaccaag tctcgctctg tcgcccaagc tggagtgcag tggcgcaaac ttgcctcatt 209040 gcaacctctg cctcccgggt tcaagtgatt ctcctgcttc agcctcccta gtagctggga 209100 ttacaggcgc ctgccaccat gcctggctaa tttttgtagt tttagtagag gcagggtttc 209160 accatgttgg ccatgctagt ctcgaactcc tgacctcaag tgatttgcct gcctcggtct 209220 cccaaagtgc tgggattaca gatgtgagct accacaccca gttgcaatgg gtatagactt 209280 ttgaaatgtg tactacaaaa tattaacagt gactatctct gaatgatagg attatggata 209340 aattttgttc tttttgcata tctgtatttt tatttttcca cagtaaacat cttttacttc 209400 tgtaataaaa acttcattaa aaaatccatg ctgcaattga ttaattatat actaactttt 209460 ttttactctt ccctcagtac agaaagatta ttctgtattt accaaatctt tacactttat 209520 ttgcaaatca ttttgactgt ctgtttgcaa gaggtcaaat ttgcactcaa gttcagcttt 209580 cgttcattat ccatgagccc aagagaaatt gtgtcaggtg gacatcaggt agctgaggcc 209640 aatacaatat tattcctttg ggttgttgag aaatcatagc agaggaaagc ctgtgttgat 209700 aatagagtac caccaggaat ctaggtcttt acagctgctg gcctgaccag caagggtaaa 209760 atatttcagt cacgcagcca gtgattatta accctagctc tatattccag agaggaagag 209820 ctagcctttt tgggttgtga tctgtcactg attgcagttg cacatatact agccatgagg 209880 tctacacaca tgtgaagagc atgctacaca catagactag atacactgac tcatcagcct 209940 ggaaacagtg cctgaccctc actttgattg tttgaatgtg tcctgaccca ttaccctgcc 210000 tttggatccg ttcctgtttt tttttttttt tttaaagcat tttatctgtg aattaaaata 210060 gtactttcca ttgcttcatt tttttttccc tgaggagttt agctttgttt aattagaaac 210120 aagacaacaa tcattactgg tctggtgcaa tcttgtttag gactcctctt ttgcttagaa 210180 ctatacctgg attagggatc actgtgattt agagtgtgca gtatgaggtt atttaaatac 210240 ttaatagtat atttgaaatg aaaagagtag aaattaaaga ctgaatcatt taccaagaaa 210300 taacagagga gaccaattta cttctgtaag atttagtaga ggctgttccc ttctttataa 210360 ttggctttgt ttcagttacc agttaagtgg ggtgaactgt tattaaaagg ctatgggtaa 210420 ggttacagta gcattcttct aagaaaaact acaggagtag tcactgtgca gctatctgct 210480 ttgtacctgc caatatggca gtagatatgg aagggtcaga aaaacaggac ttcatgttca 210540 ataacttttc ctttttcctt tctttccctt atttttttca tgtcttgtat gcaagatagc 210600 atgcctattc tttaccttca atgtattttt gaatttttaa tccagatcat attttatcac 210660 aatttgtaac atgtagctaa taaaaatggt tattacatga gaacttgctt tacaaattat 210720 agatcaaatt tttatacaaa ttattatgtc accatagaaa aatagttacg atttatctgt 210780 ttagtcttag aaaaattatt tcacatatta gttaaggctt ttagttttga gtgagcaaaa 210840 tccaattcaa actagctttg ggtagaggtg ggggtaaaag agaggaatgg atttcaatgg 210900 aaggtttact tgcgtgtctt ggctaactgc aaacatggca gggtgcaacc agaccttagt 210960 gatcacagac ccagggactc agaccctgtg aggaccttag ccttaccgcc actcttctcc 211020 atgtgtcagt tcgcgttctc tgtctgcaag tatgcatttt ccctaaggtg ggaagcagag 211080 ttggcaacag ctgccagggt tgacttcctg tggcattctt gcagttagca aatattagag 211140 aaggactctg cttggcccag ctttgggaca cacctctgga ccaactagct gttctcagga 211200 ggcagtaaca tgtacagcag gtgatccctg gggctcgccc tgtgaaatca ttgtgagcca 211260 atcactacct ccctccctga tgctgatgtc tactatgttt gatgtctctg aacttccatt 211320 tcctcaattg tgaatggcac cctggttcct accttgctgg atagnnnnnn nnnnnnnnnn 211380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 211440 nnnnnnnnnn nnnnnnnnnn nnnntccttt tttatggctg catagtattc catggtgtat 211500 atgtgccaca ttttctttat ccagtctatc attgatgggc atttgggttg gtttcaagtc 211560 tttgctattg tgaatagtgc tgcagtaaac atacgtgtgc gtgtgttttt agaatagaat 211620 gatttataat cctttgggta tatacccagt aatggcatgg ctgggtcaaa tactagaagg 211680 ctacagtaac caaaacagca tggtactggt accaaaacag atatctagac cactggaaca 211740 gatcagaggc ctcagaaata atgctacaca tgtacaaccc tctgatcttt gataaacctg 211800 acaaaacaag caatggggaa aggattccct atttaataaa tggtgttggg aaaactgact 211860 agccatatgc agaaaactga aactggaccc cttccttaca ccttataaga aaattaactc 211920 aagatggatt aaagacttaa atgtaagacc taaaaccata aaaaccctag aagaaaacct 211980 aggcaataca attcaggaca taggcatggg caaagagttc atgactaaaa taccaaaagc 212040 aatggcaaca aaagctataa ttgacaaatg ggatctaatt aaactaaaga acaactgcac 212100 agcagaaaga aactatcatc agagtgaaca ggcaacctac agaatgggag aaaatttttg 212160 caatctatcc atctaacaaa gggctaatat ccagaatgta gaaggaactt caacaaattt 212220 acacacacac acacacacac acacacacaa acaaccccat caaaaagtgg gtgaaggata 212280 tgaacagaca gttctcaaaa gaagacattt acactgccaa caacataaat atgctgccaa 212340 caagcatatg aaaaaaagct catcatcact ggtcaagaga aatgcaaatc aaaaccacaa 212400 tgacatacta tctcacacca gttagaatgg caatcattaa gaagtcagga aacaacagat 212460 gctagagagg atgtggggaa ataggaacgt ttttacactg ttggtgggag tgtaaattag 212520 ttcaaccatt gtggaagaca gtgtggcgat tcctcaagga cctacaatta gtagttattt 212580 ctaggtctga cgggctgtct tttagtttgt tttcttattc tgaggtggac ttaaaccaat 212640 tttaaaaaca gggatgactg aattcgtgtg ttaatcttgt actacaggaa ccctttgaca 212700 ttgattcaga agcacccaag tgtttgttca ttaatccttt tttatttttg catattattt 212760 atttttcaac ttttatttta aaaatcaggg gtacatatgc aggtttgtta caaaggtata 212820 ttgagtgatg ctgaggtctg gcatatggat gaatctgtca ctcaggtaat gagcatagta 212880 cccaatgata gttttttgta cccaatgata gttttttgtt ttctttgttt ttttttgttt 212940 gtttgttttt tgagatggag tctcgctctg tcacccaggc tagagtgcaa tggcttgatc 213000 tcggctcaat gcaacctccg cctcccagat tccagcaatt ctcctgcctc agcctcccaa 213060 gtagctggga ctacaggcgt acaccaccat gcccggctaa tttttgtatt tttagtagag 213120 atggggtttt accatattgg ccaggctggt tttgaactcc tgacctcagg tgatctgccc 213180 acctcggcct cccaaagtgg tgggattaca ggcgtcagcc actgtgcctg gccccaatag 213240 atagtttttc agtccttgcc cctgttcctc cttcccactt ctagttatca ccagtgtcta 213300 ttgtttctgt ctttatgttc atgtgtacca aatatttagc tcccacttat aagtgagaac 213360 acatggtatt tggttttctg tttctatgtt agtttgctta gatagacctc cagctgcatc 213420 cacgttgctg caaatgacac gatttcattc ttttttatgg ctgtgtagta ttccgtggtg 213480 tagatatacc atatattctt tatctaggat aactgatggg caattgggtt gattccatgt 213540 ctttgctatt ttgagtagtg ttctgatgac catatgggtg catgtgtctt ttcaatagaa 213600 caatttattt tcattactct tatcaggata cctgggagga acttctccta cgaagttaat 213660 ttggggggac tcctgaagat gagtgaaacc ccttattaag cacttagagg gtcgaaagtg 213720 tacaagggaa cgttcaggtg tgacagcttg agagacatgc atattccacc cccacaccag 213780 agcttagtga accgtctttt ctattttctc ccaaagcacc aaaatggccc agaaattgga 213840 agatggaaaa tggacttatt tatgagtctg ggaaggcagg gcagtaagca cagtcctgtt 213900 cagggttctg agttttaccc tcttgctctg attgcgagat cattttcctc ttccttgctt 213960 cttcagctta ggacaagaac agtttggaaa ttgtttctac tactttggac accatagttt 214020 agatttcaaa tgagtacaag tgggaggaaa gcttggataa ttctctggaa ataatcgaac 214080 agagtgaagg agaggggtct acaggtgagc tgaatgctgc atggcattga agtaatcaca 214140 ccagtcgtca caattctctc ctctttgatg gttatctgtt gtcccagaag gaacaatttc 214200 agaaagtcct tttctggact gtagaatagc acttgcttat ttgatgagcc ctgagaagca 214260 ttactgaaag cggttcattg tccctgaggt attacaatga gatggtggtc actgatttca 214320 ttatgttttc ctttattgca gctgttggtt tgatcctttg ccaggtgctt aaaacaattg 214380 tggttttgca gatggtaagt tagaggttgg acaaaaaaag ggatcatgtc actgccctgg 214440 ccaaaatttc aacagactgg ggtctagtga gggcaaatag atagaggctt tcctcttcac 214500 tttgtgttat ttagaaaaag aaactttcca ggacaaattt ctttcctaga attccttttt 214560 taaaaatttt ttttctttga aaatttactt agatgcaaat aatatatttt tcttcctttt 214620 aaataataaa agtaagatgt ctcttggagg tggtggttgt cactgacaag attaactaga 214680 actgactagc tgtaaaaata taatttggga tgcattatta aggcatgcca tttttatttg 214740 catgccattg tgtacagatg tggttgtgaa atagttcaaa tcatggcaca ttgaatgtcc 214800 tcactggatt tttaggaatg tgttcactga gacagccaaa tcctatttca ttttctttgg 214860 ctcattgcat tggctgtaaa ttggagatat tcactttaat atgtgagtca aaatttattt 214920 ccaaacataa tactgcagtt gttctgtcac agaatataaa tttcttattt atttccttaa 214980 tacgttgctt tctacttttt ctttttttct ttattttatt ctggagtatg tggaaaggtt 215040 ttccagaaag atttgcatat gccataatct actgatgaat actttttttg ggttactctt 215100 tcatattttg ggagatataa ctatggaagt gttaggaatc atgggttctg gaaatagttt 215160 tattactgct tctgaaatgc cctcccaatg ataccatata gtaattccat cagggaataa 215220 tatttttatt atagtttaaa atataactta atatttaggt gctcttgttc agtcatcgtc 215280 aagttctttt tatttcacca accctaccat ggcactcctg aaagacttgt gaatgcgaca 215340 gacctggatt taatcatggc tttgccatct gctagccaag agaacttgaa caagtgagtc 215400 aacttcttgg agtctcattt tctgcttctg taacatggga actagggtaa tctaactcat 215460 tgcttgtgat gattagatga ggcaaaatgc tgagttcacc tannnnnnnn nnnnnnnnnn 215520 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 215580 nnnnnnnnnn nnnnnnnnnn nnataaccgc taggacccga gaaccggcaa ggagaattat 215640 actgcgagat tagcctatta aaatgcaatt ccacttggtt tcagaaacct tcttgtgtat 215700 catagtgtga agtcacttat cttaggcttt taaaatggga taaatattga gtccaaagtt 215760 ctggaagaag cctagaaaga aggcagagtt attaactttt agatataggg aggaacctta 215820 aaattattca gttcttcatt cattcactta ttcattgact agctttacta acaaagccct 215880 atgcaagacc ctggaaatgc aatgatagaa aaacctggtc cctaccctca cagaacttgt 215940 gaggtaaagg gggatacaga ctgataaacc agcaattaga tgatggtgtc aagatagagg 216000 tgaaggcagt gtcttatagg atccaaactc cactcagtcc tggtggtggt tgagtctggc 216060 tatcagaggt ttcctgatta aatctggagg gtgagtcaag ggagcatggt gaagaaggag 216120 ggaatgcatg tttagccatg tgaatgagtc catgagtgaa gaccaggagg aaaggcagag 216180 cgcggggaat tctatgcgta atatttaaca aaattaatgt actgttaaac aaagacattt 216240 ctgggccatg gatttaatcc tagactgtgt aaaaaccaag taattgattt cctttatact 216300 ttaaaagcat ttccatgtat ttgatttgtt tgtgtgtata aaagggaaat accacaacaa 216360 gtttaagggt ttctagttct gctttctcat catagtcttg ataacttgga actaaaaagt 216420 ttttgctgaa attgtctgtg actctttata aatcacactg cccctcaaac acatttaagg 216480 atggtgaagg gtctgacacg taggtgggaa gttctgaaga tgccgcagct ctccctgttt 216540 tccttgttac ttaagaagag agctagaaat gagtgtacat cagattattc tcatgttcta 216600 agtgttttgg ttgaagaggt aaagtgtttg gcttgaaagc atacaaattt tcatccacta 216660 cttagtgtac aaacttgatt acttaagaga ttgagtaatg gcctccagtg aaacgcattc 216720 tttttaaaaa gcaaagtgaa ggatgctatt taagtcagaa ggggcaaaat tggatatttt 216780 atgagtttat taatcattgc aggcatagaa gtagtgttcc ttaagatgtg ttttagacag 216840 agtccctggg atgagttata taagcagatc tggttgtagc ttcagcagcc agatactacc 216900 tttgagtatt acttcaagga aaaaggactc cactgagctc actgcttctc tttcattatt 216960 atttcagaag gttgtgtggc gtagaggggg ctcaggccta cctatacacc actagctatg 217020 ttgccatttt atattatttc tataaggtgc caacagaagc tgctcatcag atcagacaga 217080 catagcccag gcaagtattg atttacagat gatctttggc caggaagaca tggtatcagg 217140 gtagagtctg gttatgggtc aatgcagtgg ggaccttagg tcctacaggt ataactgaga 217200 gcctgatcca ccaggcctta gaaagcttca gggtgagaca gtccagcacc ctggatagct 217260 cctttaacag ctgtggccgg taagcaggca cttatttgct aaagaactca agcccattta 217320 gctggcttca tctgctttgt agagctctgt taaaaagagt tcctatttct ccacatcctc 217380 tccagcacct gttgtttcct gactttttaa tgattgccat tctaactggt gtgagatgat 217440 atctcatagt ggttttgatt tgcatttctc tgatggccag tgatgatgag catttcttca 217500 tgtgtttttt ggctgcataa atgtcttctt ttgagaagtg tctgttcatg tccttcgccc 217560 actttttgat ggggttgttt gtttttttct tgtaaatttg tttgagttca ttgtagattc 217620 tggatattag ccctttgtca gatgagtagg ttgcgaaaat tttctcccat gttgtaggtt 217680 gcctgttcac tctgatggta gtttcttttg ctgtgcagaa gctctttagt ttaattagat 217740 cccatttgtc aattttggct tttgttgcca ttgcttttgg tgttttggac atgaagtcct 217800 tgcccacgcc tatgtcctga atggtaattc ctaggttttc ttctagggtt tttatggttt 217860 tagttggtgg gactgtaaac tagttcaacc attgtggaag tcagtgtggc gattcctcag 217920 ggatctagaa ctagaaatac catttgaccc agctatccca ttactgggta tatacccaaa 217980 ggactataaa tcatgctgct ataaagacac atgcacatgt atgtttattg cggcactatt 218040 cacaatagca aagacttgga accaacccaa atgtccaaca atgatagact ggattaagaa 218100 aatgtggcac atatacacca tggaannnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 218160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 218220 nnnnnctcag taaactatcg caagaacaaa aaaccaaaca ccgcatattc tcactcatag 218280 gtgggaattg aacaatgaga tcacttggac acaggaaggg gaatatcaca ctctggggac 218340 tgtggtgggg tcgggggagg ggggagggat agcattggga gatataccta atgctagatg 218400 acgagttagt gggtgcagcg cacagcatgg cacatgtata catatgtaac taacctgcac 218460 aatgtcacat gtacactaaa acttagagta taataaaaaa aaaaaattta aaaaaaaaaa 218520 gagatcttag ttcttttggg cttggggact cactcttgtt cacttaaagt ggattggttc 218580 ttacatttat tttcatagtt gtgtctggtc accttctggc ttgatgtatg cccctatgtc 218640 tggaaaaggt tagagaatgg ggtagaagtg gaggctgccc gcccatcatg taactgtttt 218700 atcttttcag agatacaatt gggatcctaa ctctttggtc tccgtatttc cacacttgct 218760 cttatacgat tcagtttcca tgcaacagca ggagagatat tttagatata ttaatcaggt 218820 cctatggtct tgagtttaca gctctcagtg taaatcttac tctcaagaga aaaattttcc 218880 ttctgcagct gaaaacattc gacatattct ctctcctatt ccttctcccc cattcactgt 218940 actccaggca caccagcttt tatttttatt tattttttgc tattcccccc aacacgccaa 219000 catgttcctt cctcaggatc tcagcacatg tggttccctt tttccctttg cttgaaatac 219060 ccagatcttt acttggctgg tttcttgtca ttcagattct gcccaaagtc actttctcag 219120 aagtagtgtt acccttccac gagtaatact actcttactt ctctttacag ctctcaaatt 219180 cttatgaagt tttcctattt attcatttgt ttgattattg tctgtctgca tcaggtaccg 219240 tgcaaacttg gatgtaaact cagtgatagc tgatttctgt tcagcattgt ttgttgctat 219300 agctccagtg cttttagtca tgttgggcac gtccctacta aatagtagaa tatggcgaag 219360 ggtcagagtc atgatagata gccggatgtg gtggctcatg cctataatcc cagcactttg 219420 gtaggctgag atgggcagat cacgaggtca ggagttcaag accagcctga ccaacatggt 219480 gaaaccctgt ctctactaaa aatacaaaaa ttagccagtt gtgatggcat gtgcctgtaa 219540 tcccagctac tcaggagact gaggcaggat aattgcttga actcgggagg tggaggttgc 219600 agtgagctga gatcgcgaca ctgcactcca gcctgggcga cagagtgaga cttcatctca 219660 aaaaaaaaaa aataataatg atagataaaa actgctagag gctctctgag aaggaagaaa 219720 tgtcactggg ttaggttggt aagagaagtg ttaatgcaag tggtacattt gatataagca 219780 tgcaaataaa tggtagtttg gaggaaaatt ccagaaatgt gaaacagtat tgagaaattg 219840 agtaagccag ctttgagaga acacacggct tattgtcctc tccttctgtt ttgctcctca 219900 gctctctaaa gtgggcattc tctagggtcc tgtcttcaat ctcagcttct ttttcttctt 219960 catccttctc tttccaccta gtttcctagg gaattatata tatatatgtc tggtacaggc 220020 tgaattgtgt ctcccagaaa gatatgttga agtcctaatg ctcagtgcct cagaatgtga 220080 ccttatttgg aaataatgtc attccaggtg taattagtta aggtgaagtt atactgtggt 220140 gtaacccaca gtatacttcc agtatatact tcagtatatg ggcccttaat ctaatgtgac 220200 tgatatcttt agaataagaa gaaaatttgg acacaaacac agagaagaga atgtcatatg 220260 ataacagaga gagagagaga gaagagagag agagaggaga gagacacgag gagagagagg 220320 gaggagagag agagagagaa ggagaaagaa agagaggagn nnnnnnnnnn nnnnnnnnnn 220380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 220440 nnnnnnnnnn nnnnnnnnna aggattatgc aagctctggg tccgaaaagg aggctatgaa 220500 ctgccacagt ataaataatc tgcaaaaaaa aaaaaaaaaa cacctgcttg gttcttgttt 220560 ggacatcata aaaatgctta tatttgtttc tgcagtttac tatttgtaca gcttaatgtg 220620 ctggtagcag gatgttcttt ctgaattgta agctcccaga gagctgcatt tggccctgta 220680 ggactaattt atcattttcc tgtttagaag ggctttgcac atacactttt tataataaga 220740 gtgtttctta caaggtttgg taagattcag ggaatgctta tattattatg aaaatcaaga 220800 ggaaggtttt agagttattt ctccattatt aataatgtgc aaccttcaag aagtattcag 220860 accattcttt tcatcaagtt tctttaaaat taattgagga aattaattca aatccccacc 220920 cctggaatat ccgcagagag ctgattctgt ttctgtggct gctggataat tccatctgga 220980 catccagcta tcatctcaaa tgcagcatgt ctagaattga acttatccta ccccctgatg 221040 actggccttc ctcttggtga ccaagtcatt catttctcag ttcattcagt ctatgtctga 221100 acctctttaa ctcttttatc tcctggataa cccatattta attaccttca agcaatgtat 221160 atcctttcat tataatatcc tttattctat tccccttctt tccatttcac aaataccaaa 221220 aagtacagat ttttagtaca tctaagctag ttgaatatca gccaaattgg tcttcacgct 221280 ttgattcttt cccttctctg gtccctccta tatacctctg ccagattaat ctgcattaaa 221340 gactctttca tcagccgggt gcggggctca cgcctgtaat cccagcactt tgggaggcca 221400 aggcgggtag atcacctgag gtcaggagtt caagaccagc ctggccaaca tggtgaaacc 221460 ccgtctctac taaaaatata aaaactagcc aggcatggtg gtggacgcct gtaatcctag 221520 ctactcggga ggctgaggca ggagaattgc ttgaacccag gagacggagg ttgttgtgag 221580 ctgacacaat gccactgcac tgcagcctca gtgacagagt gagactctgt ctcaaaaaaa 221640 aaaaaaaact ccttcatcat acctctccca tgttgaaaaa gtataatgtt tttgtgttgc 221700 taaagcccac aaactgatcc taatttccat ttattctttt atttatttat tgagtgactc 221760 tgagaatatt gggccctcac ctttaaggac tttacagtca gtatgggaca gaacatgggc 221820 aatcaaatat atgcaataca atggaataaa ctaatatcga ggtcccagga gagagagaat 221880 ttctgcatta tcttcagggg cttaacaaca gtcacttttg attagggttc gaagaatttt 221940 tacaggtaaa tctggaaaga aattcccagc aaagaaatgg aatcatcata tttgtagaag 222000 aacaaggaat tcactgtgtc tggagtgcct atttcacaag taaaaatggt gactttaaaa 222060 tgactagaaa gataggctag aacaagattg tggcagtcct tgaactcttg tttaaggacc 222120 attccatggg ctatggaggt cattaaagga tcttgtactg cgtattgaca tgatcagtga 222180 tttgctttat gaccactaat agagtggcaa tgtgcagaat gtctcgcaac aagaaaaaag 222240 acataagcaa acggcttaga tgaaggagaa ggcaaatgga aacaataaat tattgcaagc 222300 atcctggtga aaggtaatgc agctaactca gcaatggtaa gtggatgaaa atgcatttaa 222360 ggagatagac tcaatagagc tatgcaacag ctctggaaac gtcagagcca gaggctgcaa 222420 taagaaacaa tggaaataac taactcccca gtttgaagta cggatgccgg agggagtggc 222480 aagggaactg tcacacacag caggcagaag gaggggctgg tggcagaggg aaacacaggg 222540 gagtcactga gaaaatcagg ctggggcagg agctaggagc aagatttggg agatattggt 222600 gcagctgtaa cactttaggc cccaaatatt atgttattat attagtttcc taggcaccca 222660 gcaatctttg gtgttcttgc tttgtagatg tttctcttct gtctcctctc tttcttnnnn 222720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 222780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnactg agaaaatgat gttattataa 222840 actggtttga gggtattgtg gtttagatgc tgtccttaca aatttgagct ctgttggttt 222900 ggagatttaa tatctaataa taatagttaa tgtgtaatga atacttgccc tgctccaggc 222960 tctatgttac gtgtcctgaa tgcatcatct catttaatcc tccataaaat ttgaagcagt 223020 cagcattgta attaatctca cttttcagat gaggaaacca aggtatgtaa gaaacaaaac 223080 cagtgttgaa tctgactagt acgactgcaa agcctgactc ttaaccattg tgttctgttg 223140 ccttctccaa gggaaaggag tgcttccaga aaggccattg gaagtgagga gtgtcacctg 223200 ataatagctg gctcctcatc ccactaggtt aacaggcaac agatgggggc cacagagttg 223260 gctggagtta gtcctggttg ccaagggtaa atggggctgt taccatgcaa tggatagaaa 223320 ctaggatgct cctgtgtgtc tccttatatc ctaccaggtg tagcatgaag gttaaggaca 223380 attccgtcct cttatttgga gaggagacca aggccctgta ggactaaagg tttgggtgag 223440 ctgaaagcca agggcaattg gcccagcttg gggaggagag ttacaaatac atttgtgact 223500 atcagaccag aaacagactg cggtgtatcc tgcggtttgg gtacctgctg cttgttcttt 223560 gctggggtat ctgaagactg aaaacacagc tcacacttag cctttttcct attctgtgtg 223620 aaagaactgt agtagttttc tcttgcttaa caaggttcta gtggtgaagt ttattgctta 223680 gtctgtgagt tgtagggaaa taaccacagg atgggatggt agcagaacga gaaaagaaaa 223740 gaagattgta gatgccaggc tggtgtcggc ttgaaatttt taaagtatac agttcttctt 223800 tatggattat taaaaaaaaa cagcaaatga atacacaaga ttaaatgtta agcagtacaa 223860 cattgtacat gatgaaaggt taaagtcttt ctctggtctc attcaaaaat ctacagtctc 223920 ttgtagtata gtttgaagtc aggtagcgtg gtcctccagc tttgttcttt tggcttagga 223980 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 224040 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn ttctgtgctg catgtgagta 224100 ccgacttaaa ttatatttta agaagggcta ctttgaaact ctctctctga aaactctatt 224160 tctaaaagct ctaccctcac aacaattttg gcaagcagtc ttggtaaaac caaaccaaac 224220 caaaccaaaa ccaaaaaacc ttatctgctg agaaaatata accacataaa atatggtgct 224280 acaaaatata gactgtgtga actgaaggtg acttgcccaa aggactcctg aagcaattgg 224340 ctgctgtaga aattaagtcc acgggaggtt ttttgttctg tttttttttt tttttttttg 224400 agatggattc tcactctgtt gcctaggctg gagtgcagtg gcgcaatctc ggctcactgc 224460 aacctccgcc tcccgggttc aagcgattct cctgcctcag cttcctgagt agctgggatt 224520 acaggtgtac accaccatac ccaggttttt tttgtatttt tagtagagac ggggtttcac 224580 catgttggtc aggctggtct tgaactcctg acgtcgtgat ccacctgcct cggcctccca 224640 aagttctggg attacaggca tgagccaccg tgcccggccc atgagaggtt ttgtttgcac 224700 ttcaagaagg acagaaaaag gcaggcaggc tgggagcaac atagtaaggc tgaggaagtg 224760 ataggaaaac agcctccaaa aggtttccct gtagattctg actggctaag tttcctgaaa 224820 taatattaat tctgtcctct tgcttttaat aggacataac gactatatgt gtccagccac 224880 caaccagtgc accattgata aaaacaggag gaagagctgc caggcctgcc ggctccgtaa 224940 atgctacgaa gtgggaatga tgaaaggtgg taggtacatc tctcccaggg gcccttgggg 225000 gatggccctg gccaccgccc agtgctggct ctacccattg gaataacacc atgggaattt 225060 tgtgtttttt tcttttaatt gttttttttc tattcttatt tttctttgca acaaaagtat 225120 tttcataatc cattttattt taaaaaggtg gaagtgtctg gaactggaaa ttctaacatg 225180 gcattttgtg ttttggattt tcaatgtaaa taattatatt ttaaatcaaa ggtgtgtggg 225240 aggcggtgat ggaaggaaac gaagagtgct tagtaaatta ttctagaaat atttttcagt 225300 tactgtttat gttgcaaatg ctagaaaatg atatctgagg ataaactttc cctaaattga 225360 gacttgtaaa tgtgaaagct gagtagctaa tttatagcct tccagtctgt tatcatccct 225420 taaggaatgt gaatttcaat caaaaggcag ttttctcctt tagaacctga gtgaaccagc 225480 cactttctta acctcagtgt ctagcatggt gctggcatag ttgattactg agcactacac 225540 taacaagtgt cagagcatgc atggtttgtg actgtgggtt tgtgtttttg tggtctttgt 225600 ggctgtgtgt gtgtgtggtt ttctgtcttc tcatgtatcc gatcttccag ttttgtcata 225660 caggaatctg gaaactgaat cccagttctg ggaatattag gagccccata aatgtggttg 225720 cctgattgac ctcattgtat tcttgggagt ctcatcttga ggaacattgc ttctagtctt 225780 ggatagcctt cagtgtagtg gaagagaaca agtagaaaat gtgtaattaa aataaagtca 225840 tgaggctgag gtgggcagat catctgaggt caggagttcg agaccagctt ggccaacaag 225900 gtgaaaccct gtctctattg aaaatacaaa aattagctgg gtatggtggc gagtgcagta 225960 ggcccagcta cttgggaggt ggaggcagga gaatcacttg aacctggcag gtggaggggg 226020 cagtgaactg agatggcgcc actgcactcc agcctgggtg atagagtgag actctgtctc 226080 aataaataaa taaataaata aataaataaa taaataaata aataaataaa gtaacggatt 226140 catttagtgt ttcagaagga tactgaaggg agggaagggc tgatgatggt gctacctgct 226200 gattgtaata gggaaaagcc cgtttctttt ctgaaggagg tgaagcttgg ggtgatttaa 226260 ggagaacaaa atttcaatga aaaggaatag tgattttgca aatagtgggc agctaacctt 226320 taaatcattc ttactgggac gcaggaggaa ggagaggaaa gaccaagaat ggagattatg 226380 atgaagacaa gcttgattgt taacaagctt acagtgacag gtttcatagt cccggggtca 226440 taaatacgcc agacaggttg aggtttggaa tgcagcattt ggaataaatt ctcctggtga 226500 agagatgcaa tgttgaattt acgcattctg tgagctgtga ctatgactat acatcttgaa 226560 catctgaaaa agcagcttta attcaaaggg taattaattc caagaattta acagctacat 226620 tcagaaaatg acacttgagt catatggatt aaatatttaa ggaattcatc tttctttgta 226680 ctgttggaga attagtcagg cttaattaaa cttacaaaat gcgtcttaag gtaacttggt 226740 aagtgacagg aatataacag ctgcataaga aaagctttat ttgaaacagt ggagtcgagg 226800 tttaatattc ttctttggcg attatatgta ggttaagcac aggctcttcc atacattctc 226860 cttgaaagct gaaataatca agtcatgaat atgtccaaaa caatttttaa aatgtgaggg 226920 gtacccatgc attgacccca tttcataaaa ccgattctgt tttttttttt gtaattaata 226980 tccagatacg gtctggctgc atgaatataa attacgcatt ctcattttta atctaacaaa 227040 aattcatata tgcaaagaca taataaaagt ctccccactg ttttctccta ggaatctaga 227100 taatttgact gtacacaaca gactgtggat ggctccatac acacttgcac atgtatattg 227160 atgactgtaa aatatatatc tgtattagtt ttctagggct gccataatga aataccacag 227220 gctgggtggc ttaaacaacg gaaattaatt ttctcccaat tctggaagct ggacatgcat 227280 aatcaaagtg ctggaatatt tggtttctag tgagccctcc cttttttttt tttgagagat 227340 ggagtcttgc tctgttggcc aggatgggag tgcagtggca ctatctcagc tcactgaaac 227400 cttcacctcc caggttcagg cgattctcct gcttcaactt cccaagtagc tgggactaca 227460 ggtgtgtgcc accataccca gctaatnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 227520 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 227580 nnnnnnttga tctgtgacct tacccccaac cctgtgctct ctgaaacatg tggtgtatcc 227640 actcagggtt gaatggatta agggcggtgc aagatgtgct ttgttaaaca gatgcttgaa 227700 ggcagcatgc tcgttaagag tcatcaccac tccctaatct caagtaccca gggacacaaa 227760 aactgcagaa ggccgcaggg tcctctgcct aggaaaacca gagacctttg tgcacttgtt 227820 tatctgctga ccttccctcc actattgtcc tgtgatcctg ccaaatcccc ctctgcgaga 227880 aacacccaag aatgatcaat taaaaaaaaa aaagaaaaga aaaaaaaaaa aaaatgaaca 227940 aaacctccaa gaagtttggg acagaattaa acaaccaaac ctaagaataa ttggtgttcc 228000 tgagaaagaa gagaaatcta aaagtttgga aaacatatct ggggggataa ttgaggaaaa 228060 cttccttagc cttattagag acctagacat ccaaatacaa gaagctcaaa taacacctga 228120 aaaattcatc acaaaaagat cattgcctag gcacattgtc ataaggttat ctaaagttaa 228180 gataagaaaa ataatcttaa gagctgtgag gcaaaagcac caggtaacct ataaaggaaa 228240 acccatcaag ttaacagatt tctcagcaga aaccctataa actagaaggg attggggccc 228300 tatcttcagc ttctttaaag aaaacaatta gcagccaaga attttgtatc cagcaaaact 228360 aagcttctta aatgaaggac agatacagtc tttttcagat aaaaacaacg ctaagagaat 228420 tcgccactac caagccagca ctacatgact acacgaactg ctaaaaggag ctccaaatct 228480 tgaaacaaat gctggaaaca catcaaaaca gaacctcctt aatgtgtaaa tctcattgga 228540 ggtataaaac aaaaatacta ctaaaaaaaa tccaaggtat acaggcaaca aatggcatga 228600 tgaacagaat agtacctcac atctcaatac taacattgaa tttaaatagc ctaaatgctc 228660 cacttaaaag atacagaatt gcagaatgga taagcaatca ccaaccaagt atctgctgcc 228720 ttcaagaaac tcacctaaca cataaggact cacataaact taaggtaagg gtgtggaaaa 228780 agacattcca tgcaaatgga caccaaaagc aagtaggagt agctattctt atatcagaca 228840 aaacaaactt taaaacaaca gcagttaaaa aagacaaaga agagcattat ataatgataa 228900 aaggccttgt ccaaaaggaa aataccataa tcctaaatat atatgcacct aacactggaa 228960 ctcccaaatg tatagaacaa ttactactac acctaagtaa tgagacagac agcaatacaa 229020 taatagtggg ggacttcaat actccactga caatactaga caggtcatca agacagaaag 229080 tcaacaaaga aacaatggat ttaaattgta ccctggaaca aatggactta acagatcttt 229140 acataacatt ctacccaaca accacagaat atacattcta ttcatcagcg tatgcaactt 229200 tctctaggat agaccatatg atatgccaca aacaagtgtc aaaaaaacta agaaaattaa 229260 aactatgtca actactctct cagtccacag tggaataaaa ctggaaatcg actccaaaag 229320 gaaccttcca aaacatgcaa atacatggaa gtgaaataac ctgctcctga atgatcattg 229380 ggtcaacaat gaaatcaaga tgaaaatttt aaaattcttc gaattgaaca ataatagtga 229440 cacaaccatc caaacctctg ggatacagca aaagcaatgc gaagaggaaa gttcacagcc 229500 ttaaatgcct actcaaaaac tctgaaagag cacaaataga caatctaagg tcacaaatca 229560 aggaactaca gaaataaaaa caaacgaaac ccaaagccag cagaagaaag aaaataccaa 229620 gatcagagca gagctaaagg aaattgaaaa aaaaatacaa aagataaatg aaacaaaaag 229680 aagctggtta tttgaaaaga taaatgaaat tgatagacca ttagcaagat taaccaagaa 229740 aagaagagag aaggtccaaa taagctcaat tagaaacaaa caggagatat tacaaccaac 229800 cccacagaaa tacaaaagat cattcaaggc tactatgaac acctttacac acataaacta 229860 gaaaacctag aagagatagg taaattcctg gaaagataca aacctcctag cttaagtcag 229920 gaagaattag aaatcctgaa caggccaata acaagcagca agattgaaat ggtaatttaa 229980 aaattaccaa caacacaaaa agtccaggac cagatgaatt cacagctgaa ttctaccaga 230040 cactcaaaga agaattggta ccaatcctat tgacactatt ccacaagatg aagaaatgag 230100 gaatcctccc gtaaatcatt cgatgaagcc agtatcaccc ttgaccaaaa ccaagannnn 230160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 230220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnctta acctacaggt gctctgtaaa 230280 gaatcattgg cacattactc ttgttggctc tatcccattc cctatagata tctttctgct 230340 ctgagactaa gcagagaaaa taatttaaca tttaattatt gtgcttctaa atccactttt 230400 acctcttctt tctttacttt tctctttatt atttttaatt atttcaaaaa taaaattgta 230460 tatatttaag gtgtacaaga tgttttgata tacatataca taatgaaatg attactgcag 230520 tcaagctaat taacatcaat ctcctcacct agttatcatt tttggggggc atggagtgag 230580 agcacctgaa atctctctta gcaaatttcc agtgtataat acagtattgt taaacatagt 230640 catcatgttg tacattagat ttctagactt gttcatgcta cataactgca actttgtacc 230700 ctttgaccaa tacctctcta ttttctccac tattccatgc ctgaaattgt gggatatagg 230760 tatatagtgt gtgtgatata tatagaggga gtgatatatg tatatataat tgtgtgatat 230820 atatgtgtgt atatacaaac acacagacat acacacatgt acatatgtat atacatgcac 230880 acatacacaa tgggatatta ttcagctttc aaaaaggaca tcctgccatt tgcaacaaca 230940 tggatgaacc tggatgacat tatgttaagt gaaacaagct ggacacaaaa agaaacatgc 231000 accttacttc ttagacacaa atttctttct catagccagc acctgaaaat agggccaagt 231060 attttgcatg atttacaatt gactgtataa atgtagcata gccagttata tgatgtgtta 231120 ccatttctgc tataaaatca aaagaagaga tcagaacatt taaaaacttc cctgtggatt 231180 tctacctctt acctaagctt tgttcttgtt tttttaaacc tcatgaacac gaagctttag 231240 atagcggagg tcatgtatcc ttgggctcaa atatacagtt tcttagcaat ctttgattgc 231300 tacattgccc ttttttgtgt ttttaactgg ccttccctga cttaaaatat actttaaaaa 231360 ataacaaagg tggtatttag tttgcacagt atggaattaa aggtaaacaa ctttaaatta 231420 aatttggttg gatgtataaa ttattaaaat atcctttctc tcatggctgg gtaagtctgc 231480 attttccatt cagcctgcta tgtctctttc catgagaaca ctcccgaaga atggggccct 231540 gcttccaaac aagccaagca ttttgtagta aattttaaaa agctaaattt cataataacc 231600 tttataattg ctacctgaaa atggagtttg gaatggcacc aaattattaa tcagtagaag 231660 gagaatagat tgcaaaaagg taattatatc aaattgaatg cttcttgaaa tatattctgt 231720 taaataaaat acagttcctc ttccctgttc tcatttgtaa gcaatgagga caattcaggt 231780 agcatgaatc aggaatcaga gtacttttct gttccgcaga ttggcttaat cattttgggc 231840 tcacttcaaa ctgtagatga gcattgtcct ttaacctgcc gggcagcaga ggtgaccacg 231900 ttcactgcaa agcccagaag tgagttgttc atctgggtta gggtctcagg aagaggcatg 231960 ttatgacttc cccacattcc tggacagttt agactgtaat tcttggttgt ttaaaaaggt 232020 gtttgaatgt attttgttca gaggcttgag taaatggctc ttattcttac actttttttt 232080 ttgcctgctt tttccagcat tagaatagtt tcagccctga caattagcct tatgctgact 232140 ggagtggatt ttttgcgtag gaccaagtgt tttgcatgat ttacaatgga ctgcataaat 232200 gtagcctaac aagttatatg atgtgaagaa aattacttaa gggtaaaaat ggattgttta 232260 ctgagaaaat gatgttatta taaactggtt tgagggtann nnnnnnnnnn nnnnnnnnnn 232320 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 232380 nnnnnnnnnn nnnnnnnntg atgtttcatt tgataaatat ttccgtctac acttccaaag 232440 gatgatgact atttttaaaa gtccaactat aataccatta tattttaaaa gttaaaacac 232500 tatgtcttta aatatcaaga gtttgtattg attcgcactt tgaaggtcga gctgatgaaa 232560 tttcctgagg ggttggatgt gacatgagag aggagtcaag tattgcatgg taattaaaaa 232620 cctttgcagc atagtccatt taccgaaaga ctatatgtat gcacttcaaa gcaggtttta 232680 aagattaaca tcaagcatct ggcttcatga gttttaactt cttttcataa atgttataca 232740 atgtcatcat ctctccagct agagaaaatg ctattattct tattttcaaa tgaggaaaat 232800 gacgcagaat tatttacata ttatgtaact tggtcccaag tcccttagat actggtttag 232860 aaaatcctag taaactggaa gtgacttatc caaaattaaa atttattttg ctctattgtc 232920 ttttgttgcc tatgggaact ttgtgcaggt aactaggcac atgtcaggac tgatttactg 232980 acctctcaag gtatctttaa ttattttggg ggatatcacg gaatgagttc tacacaattc 233040 atttgaatcg aattgaactt aagaaaattc aaatgatgca ttggctgcct cctatttatt 233100 acatgctgct cataggcata acagcatagt ctaacaagta taaaacctgt gtaactgtag 233160 ctttcagtgc agtgtgatga gggctgagaa gatagtggta caaagaagag aggtagcaga 233220 gtgaagctga gtcaatatga tgaagatttc tctagacttg aaagggctag aaaaggttat 233280 tcttggcagg aaaaaaacat gagccaaggc ataaggataa gcacaggcat ggcagatttg 233340 ggaatgtcat gtaatttgtt gctgggctgc aaagtacatg gaaggggagt gaaggaacag 233400 aaggagatga atctggaggg agaggttaaa gtgttccaga gagcaatatg taggtgttac 233460 tctaagtcaa agaggtcgta atagcatgtc cagactccaa aactctaaac aagtcataga 233520 attgctgcct tggtagggca tatcacacac atcaacccaa tcctctgtca ccatgacatc 233580 catataactg caactctata catttcccag cctatgttcc cagagtctcc agatgacatt 233640 gtctgcaaac tgcactgcag aaggctctgc tatgtcttct taaaagtaag caagactgtt 233700 ttcctttgtt acatgagcag caaaaggata gggtgctctt tgacctcact tactgtaggg 233760 tggataggaa agtcaaggaa gagtaaccca gaagatttag ttttaacttt cgcatcaaag 233820 aggtccctta gcatctgctc agagatgtca caatttctgg tgtgtgatta tgtttaagaa 233880 ttcggccttg ccactgttga agttgttctg tggaaaaaga acctctctta attttacatg 233940 atgcccaact tctcttttat tccagaatca ctcatatgct gttggactct ttccagccat 234000 gtgtgctaac ctaggcaatg tcataataga tgaattatgt ttactttgtc tttgatatct 234060 cagctctttt atcttctatt caagttccca cctccatcat tactgatagt gttcgttgaa 234120 caaagaatat gtcagatata cagaagtgtt tctccccttt tctctgtctc tcttttcctt 234180 cctttccttt agtttccttt ctctgtctgt tttctgatgc ctcattttag aaaagtgatt 234240 ttttttgtgg gaaaatcatt ttagcattag aaacgcaatg gctatcactg acagcttcct 234300 ctgatgaaac ggccatttgt catcattaca cggtcatggg agtgctaaga agacttaaat 234360 gcagggctac caccccttcc caattcatct tttatccatt ttatttctct aaggaaaggg 234420 tttgaaaaat cgctttgccc tcttggatgc agtgaagaaa ttctagctgg ctacagatgt 234480 tattgttggt cggaggcaag ggataaaatc atggtcacac cattgtagcg ccagatgnnn 234540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 234600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnngtg tggggcattt ttctctcttc 234660 ttattcttta ccttttcagc ttaagtgaag gttagtataa acactaagaa tatttctgat 234720 ggagttttca tgtgattcct tctacaaaaa cccagattta agtaacttgt tgaaaaccag 234780 agtccgctaa gttaataaac actgattgaa gaagtgattc tcatggactt tctgtgatag 234840 ctctttcctg ccctgatatg agatgaaagc tgggggatgg tatatagtat ttatttttcc 234900 ttccgttgcc agtgggactt tttttttttt tttaaaagct gttcatatct taatcgagta 234960 gcatgtgagg tcaacatggt ctattttaaa agcattttct tcgacacatt gcttttaaca 235020 tcttttagaa ctctgctgtg agacacatgg acttttttgt tggtattttt atacaattaa 235080 tgatattctc aatagtaatc tttgtgtgtg tatatatata gaaataaatt ctaaatgtaa 235140 gttaatatat ttattatttt tctaaacata tataaatata tatatgcaca caggctattt 235200 aattttatta gatgatgcta ttttaattca gaaaaaaatg acatttatat tttgatttag 235260 gttagtataa gcccttagag gtgttttgac aactctctta atttgtggtt ttactgttta 235320 tttgatttta tataatctaa aataccattg tttttaccaa gcatttaatt tggcagtgaa 235380 agagcgtctg acagaggtat ggttagtaga taggtctaac tgcacaactg gatggattga 235440 gctgagactg tttcctcatc agtaaaaatg atttgaagca gtggttggca aagtttttct 235500 gtaaagggcc agataataat attttaggct ttacaagggc catgcagtct ctgttgcagc 235560 taccgaactg gattatagcc tgtaaggtga cctgtaaaca catggaagtg attatgtgct 235620 aataaaactt tatttatcag aataggtaac agatcagccc tggcccgtgg ccgatccctg 235680 atttaatgtt tatttatctg atctaaatac ctttatttat ggaagggaat aggggatttt 235740 taaatctaaa gttttgatta ttcacatttt actgagaact tactctatac ctgattagat 235800 gttccgagag aaataaaaaa aaagtgtaag acataatcca taataccaca aaatttaaaa 235860 tgtatttagg aaatttattt gaggaagtaa atgtacttgt tctcatgata caatcagaaa 235920 gtaagtcagt attgataaag tgttacctgt atgagaaaga taaggaaaac aatagagaga 235980 tgtaagaaat gaaaatacca gttataaatt aaaattatta agattgaaag tggaaatgat 236040 cttcctccga gaaacaatgg caatattctc acaaattttt tacatcattt ttgttcagca 236100 tttaagataa aattatataa attcccataa catttagtat tgtctctaag cattaagaac 236160 agaaaaaaca gaaggaaaat atatttctaa aaatcaacga atacagtgtg agatgtttca 236220 ttggtatggc attatctcaa gttcaaacat tttgaaaaat gtctgcttac tctttgatag 236280 ttaaaaacaa gtatctcagc tggcgtggtg gctcaggcct gtaaccccag cagtttggga 236340 ggctgaggcg agtggatcac aaggtcagga gatcgagacc atcctggcca acatggtgaa 236400 accccatctc tactaaaaat atgaaaatta gctgagcgtg gtggtgcaca cctgtagtcc 236460 cagctacttg ggaggctgag gcaggataat tgcttgaacc tgggaggcag aggttgcagt 236520 gagctgagat catgccactg ccgtccagcc tnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 236580 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 236640 nnnnnnnnnn nggctcatgc ctataatcca gcactttggg aggctgagga ggcagatcat 236700 gaggtcaaga gattgagacc atcctggcca acatgatgaa accccgtctc tactaaaaat 236760 acaaaaatta gctaggcatg cgtggtgtgc acctgtagtc ccagctactc aggaggtgga 236820 ggcaggagaa tggcttgaac tcgagaggtg gaggttgtag tgagccgaga ttgcaccact 236880 gcactccagc ctggcgacag agtgagactc gtctcaaaaa aaaaaaaaaa aaaaaaaaaa 236940 aaaagagaaa gaaagaaaga aggaaaaaga aagaaagaga aagaaaggcg ggcattaact 237000 tcaggtattg gtaaatttgc taggtgtttg gctactgttt ctcatcagag aaatagaaag 237060 acacaccatg aaagtcaagg cctgaaaacc tcattccatg taagaatgac atccccagtg 237120 ttaagtgctt gttagtggtt aatgcgatcc tgtgaaactt agatgtgttt gtgcacacat 237180 gcacgcatat atttgaagaa ctcagaagag ttaaatcaca gcctttcaac ctgtgaaatg 237240 acagtagttc ttcttttttc ctctcccttt ggctaagtca tctttatctt ggagataatt 237300 aagacaaaaa tgcctctgac aaataaaatc agtatagaac ccctatttct tggcagcttt 237360 tgtggacaca gctgaagctt tcagaggtct tgaaaaacca tggcaacaaa tgcctttgaa 237420 gggtaagcaa aggttccaaa tgtttttaat cgctggtgtt ttttctgcta ccacttcaag 237480 catttttctt cattttttgt tcatctgatc aaaattaaat ttccaatttc cctactaagt 237540 ggttctgtcc tggtcatgcc attgactatt tccattaaag tagtagagtt tgtgcccaca 237600 tatggttgtt aagctcatca acaattccat tagaaagctt tgtttatcag tggcaataat 237660 ttcccataaa aattatagat aggttttaat gggcacattt tcaaaaggca tcaactcgtc 237720 ctcaaaatta tgtgctgaca ctgttcttac aaccatggtt cgtggcctaa ttccaccaaa 237780 tttctctctt tttcatagag aactgttgtc agtagcttta tatcctttta aagagaatgg 237840 tctgtatctc tgatactcat tcagagaaat gagtatttta gacgtaggtt gctaatttta 237900 agctatatac tacactatgt cagcactata taggttatct tgtaacctgc ttgcctggct 237960 atttggctga aaaataacaa catgtaagga aaatctattt cataagtcta acatttactt 238020 tgtaaaactt gttctggcta ctctgttaat tttccactta cgtgtgggtt agagagcaga 238080 tttgattttt ttttaagcga aagatatggc ttacctgaga aaagaacata gtggggaaag 238140 cactcctatt attttcctca tatttccatt ttcctttagc ggaaataaaa agacatttca 238200 gtttttcagt tgctaagaaa tgaaggaacc aaagacaaaa caacttaatt attaaattac 238260 aatttatttc tgtaataagc actcgttctc tctgttttcc tggggaaaga gtatgtggac 238320 tttcaatttt atccaaataa gcatcatctt tctctgatta gtgtggcagt ttcaaaatca 238380 tgtattagga agtacagagt gaatgagtag agaatttcta aattagcacc caaggttggg 238440 tggctagatt atgtttataa atatgaactt ttgtattaag tgcaatgatt taaaagaatg 238500 cctgcatcac tttagggcat ttcattaagt gctgtgcaca atatttttcc ttatacatca 238560 taaaagataa attatagttc ataaaatagt atcaattcct acttattttg tgcttttgac 238620 acctcagagc tactaataag ggctttcgtc cccaaatgac atccatttat ccatctagag 238680 acgcgcttcc ctctgttgcc tcggtctgaa gtcccgtggt gcgatctcgg gctagagcca 238740 gctcagcctg ccccgcccgc ggcccgctgc cgccgctccc cgcccgacnn nnnnnnnnnn 238800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 238860 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 238920 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 238980 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239040 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239100 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239340 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239400 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239460 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239520 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239580 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239640 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239700 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239760 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239820 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239880 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 239940 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240000 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240060 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240180 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240420 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240840 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240900 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 240960 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241020 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241080 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241140 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241200 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241260 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241320 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241440 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241500 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241560 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241620 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241680 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241740 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241860 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241920 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 241980 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242040 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242100 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242340 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242400 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242460 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242520 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242580 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242640 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242700 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242760 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242820 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242880 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 242940 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243000 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243060 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243180 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243420 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243840 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243900 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 243960 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244020 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244080 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244140 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244200 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244260 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244320 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244440 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244500 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244560 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244620 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244680 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244740 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244860 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244920 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 244980 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245040 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245100 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245340 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245400 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245460 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245520 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245580 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245640 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245700 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245760 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245820 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245880 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 245940 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246000 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246060 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246180 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246420 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246840 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246900 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 246960 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247020 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247080 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247140 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247200 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247260 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247320 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247440 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247500 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247560 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247620 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247680 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247740 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247860 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247920 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 247980 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248040 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248100 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248340 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248400 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248460 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248520 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248580 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248640 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248700 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 248760 nnnnnnnnnn nnnnnnnnnn nnnnnnnnga tcagctgtat caaatgctgc tattgggtca 248820 agtagggtga gaattgataa ttttccatct tgtcaagagc agccgtgata gagggagggg 248880 gtggagatat acttggaatg agttcatgaa aaaatgggag ggaagggatt agaagcagca 248940 agtataagca gctctttcaa aggagggaga tggggaatgg ctactgggat gccatcacat 249000 agataggaag gtggaaccct gtgcactgga ggagggagtg tcctcacaga ggaggacagg 249060 caggaaggta gagtgggctg ctttgggcac atgtggttct gtggatgttc tcttttgaca 249120 gcttcagttc ttcagggaat tgggagcaag ttcatcagct gagagtgaac atggggcaga 249180 cagtgtgaga ggtcaaagcg gcaagagtag ttgtgccaca gtcttttagg agagagggaa 249240 agtaaatgga atggggaagg aaagtaaata gcatggctgc tgagctgcgt tacaagccca 249300 cccggtgttg ggttgtgagg tgtagttgtg ggctcttctt cagtcggatt gtcagcatgg 249360 gcggctggca gagagttgaa tctgacaggg cagcagttct ggaaaatgag tatgatgagt 249420 caagaaaggg accaggaagt ggaaactgtg tgtgaggcag tgatgctgat gaatgactgt 249480 ggaaaacaat ggaggtgagg agggagtgga tgttgagtgg ctaggggaca gtgaaaaggg 249540 agtaggatcc actagcttgc tgcttgtctc ttataattag gatcaagagc ttctgccgtc 249600 ttctaggcat tctgctgctt caagggagtc tctgagattg ggttctgcat ggatgtattg 249660 aaacatgcac ctaggtgtgt ttggagtcct gccagagacc tgctttctct ttattcttat 249720 cctgaggccc tttaggaggc tcagatggaa taatttttat ggtttcttaa aacccaagtg 249780 ggttacctaa gccatcatag ttctgccccc tgttccctga gaggaccacg ggagcaccct 249840 gaaatgggtt ttccactctg ccatccccca cttgcctgct tgggtgttga cctcagccat 249900 ctacacatat cccggatgta gtgttgggcc cctggttgat gtcattcctt ttcaaatggg 249960 atcttttact acagcaatcc agcaacaaac taaatagcga tagagttttc tttcccttac 250020 aaaccacaac cacaaccaag ggaaaaacca aaccaaacca accaaacaaa caaaacaaaa 250080 gtatgtggct tcttaccaca gccccctatc tcgcccaagc cttgtggctc tttgatctct 250140 ggtgttctga aattgcgtaa tcatgtgctt gctctttttc attcattgtg ctgggcacac 250200 acttaatgga ccctttcaag ttggttttct tttatggggt aagggtaggc aggactattt 250260 tttaagattt cttccacttt gtcttccaat tgttctaatg agttttttaa aattgtgcct 250320 gtcctgtttt taaattccaa gagatattct ttgtcctcta aatgtttctt ataaatatat 250380 ataaaatgaa taatataagc atatagtttt gcatagattt gagttcgctg ttacagtgtc 250440 cttttatttc tctgaggata ttcattatag gttttttaaa aaacactttt tctggtcccc 250500 aaattatctc ttctctctag acttcctcca ttcatgcctt ccttcccccc tccctccctt 250560 cctttgctct tgctcttgat tttggaggct tgtcataaat atttgaccat ccattcattt 250620 tttaaccata acgaactaaa aatgttaatt ggagccctgt gtgttccttg agcagaatgt 250680 ttggattaat gagcttccgt gcaatgtttt ctctggaatg gattaatttc tccagatcta 250740 taatttttca atctctttcc agggggtaaa agcctggttg tctgtttcat gaaagtaaaa 250800 atgtgggtaa gagtgatccc agcattcaga atgcagactt agtagctgct tgttttcagt 250860 cctgggactt cacccaccct caccacagtt ggtatcccaa agtgtgaaac tccttagatt 250920 atctttctca agaaaatgaa actcagatat tcgtgtcctt tggccatttt tgattagctt 250980 atttgttttc ttccttttga attgtttgaa ttccttatgt attttgaata ttaacccctt 251040 attagattta tggtttgcaa atattttccc ccactctgtg ggttatcttt tcactttgtc 251100 aattgtttac tttgctgtgc ggaaagcttt ttagtttcat gctatcaaac taattttgct 251160 tttgttgcct gtgcattcaa ggttgtatcc aaagaactca ttgcccagat caatgtcatg 251220 gagcatttct cctatgtttt cttctggtat ttatatagtt tcagtgcttt tctttaaatt 251280 ttaatccatt ttgaatggat ttttaatagg gcataagtgt cacttccatt tttttatatg 251340 tggatatcca gttttcccaa caccatttat taaagaggct gtcctttccc tattgtgtat 251400 tcttggcact tttgttgtaa ataagttgat cttacttgtg cgggtttatt tctgggcctt 251460 ctaatctgtt ccattaattc atgtgtctgt ttttatgcca gtatcacact gctttgatta 251520 caatagcttt ataatatatc ttgaaatcag agagtttgat gcctctagct ttgttctttt 251580 tgctcaagat tgttttggtt aattggggtc ttttgtggtt ccatacagat ttaaagatta 251640 ttttttctat ttctgtgaaa aatggcattg gaaatttgat aggaagtgca ttgaatctgc 251700 agatcacttt ggatagcata gatttttttt aacaataata atttttccac tccatgaaga 251760 ggtatacttt tttcatttat ttttgttttc ttctatttct tttatctgtg ttctgtagtt 251820 tttagtattc aggtgtttca cctccttggt tgaatttacc ccaagtattt tgctgttgtt 251880 gctattgtaa atggaattgt tttcttaatt tcctttttgg ataattcttt attattatat 251940 agaaaagcta tggatttttg catgtttatt ttgtatgctt caactttact gcatttgttt 252000 atcaggtttt aacagttttt tgataaaagt tttggtgttt tctgtatata tgatgatgtc 252060 atcagcaaac agagacaatt tcatttccct attttctttc tttttttttt tttgagatgg 252120 agtctcactc tgtcacccag gttggagtgc agtggtgcga tctccactca ctgcaagctc 252180 tgcctcctgg gttcacacca ttctcctacc tcagcctccc gtgtagctgg ggctacaggt 252240 gcccgccacc acgcccagct aatttttttg tatttttagt acagacggag tttcactgtg 252300 ttagccagga tggtctcgat ctcctgacct cgtgatccac ccgcctcagc cttccaaagt 252360 gctgggatta caggcatgag ccaccgcgcc cggcccctat tttcttaatc acgcgatata 252420 tacaggcttg ttgaaaaaca tgaaaatgat aaagaagttt atgtattaag aggcaaaagc 252480 tatgatgttc aactcctcta aaaccacttc ttagtaggtg aacattgtta aacagttttg 252540 tgaatctgct tccagatttt ttctaggcat gttcatacac atatacacac ataatttatt 252600 tttacccagt tgcgatcatg tatcatctga tccaaaactc gctatttttc agttaatatg 252660 cagtgactgt ctttccaaac catagtatat atatatatct ctaagaattt ttcaaatctg 252720 ctatagtttt taaacatatt tattgttaca tacatatgtg tataagttac ttatttgctt 252780 atttctttga atatctttgt ctagctttgg aatcacataa ataatgagta caaatggtaa 252840 agaaatttca tgtggaagga tatatagaaa aagtacaagt ctctcttctc atccactcta 252900 tctcattacc taaaaggtta tccttagagc tttatataat acatccctga agtttagatc 252960 attttattgc ctcccaattg ttgagagtaa ggaatttagt acatatacct ttcctttcac 253020 tttcctaccc tctacctact taatgagttc gattatagtt tttcagttca cccactgtta 253080 aataatatac ctatatttat aatataccta tataatatac ctataataaa cctatatttt 253140 tgacttatca actttggaca tatctattgg tgacttgtga tgagagatga aataatttgt 253200 acatttaccc ttcttttcca ttcttttccc ctacccattc tccccttttt ggctaaatga 253260 ttgcttttag gttgataagg tttataatag ctactgttct gtggttataa aatttgtttc 253320 atattttatg tgaaatttga ttatacaact agcattcaaa acattattat gtaaatatta 253380 gttactgtaa tcacacagtg acgctcaagg aggtatttac taagcataca gatcattcct 253440 tctggatcca actcagcagt tgctttgctg tgccttacct catctttcgt ggattccttt 253500 tcttttgatt gcaatatatc cttgagtaat ttttcagaat cgatatgtac tgtctgaact 253560 ctcttatacc caaaaaattt gctttcacat ttgctaatag tttgacagag tatcaaattc 253620 tgctttcaaa ttctttcccc ttcatggctt tgaagatact gccccactat atattctaaa 253680 atccattgct gctaatgaga aattctggtg tcactctgac tcttatttct ttcatatcac 253740 ttggcatttt cttccgagaa aatattactt atcttcagaa tgatgaacct tctctatcat 253800 gtctctaggt gttagggctt ctttcattta atcctgtagg tcctcaatag gctttttaat 253860 taaagtctca ttttattcgg gctctgtgaa attttttgtt atgttttggc ttctttttct 253920 cttttgttgt ctctcttttc tccttgaatg tctttctgat agatatagca ttcccattat 253980 ctatcatgtc tttcagatta tcctacattt ttctctttgt tttctttttc taccatgttt 254040 agaattctct tacacgtaag acatcactta ctagatcttc agtcatatcc tttttattat 254100 tcagtctgtg catttttaat tttcaatttt ggcaaccaca tttttaattt ctaagaatct 254160 attttgctaa tagtactttt gtcctgaaac tttttatatc ctgcaatatt tagaaagagc 254220 acacccttat ccacagctga ttaggagtac actctgaatg cagggcacga tgggcgaaca 254280 ttttgttact ggcctcctca agcctcaatg cccagaagtt attgcctcca tcagaaaccc 254340 ttcttttgtt ctatccctca cttccaaatg aagttccagc ttaatttttg ctgtcactgt 254400 agtgggacaa gcaaatccct atttcacgtg atcattgctc aaacctctat tgacaatcct 254460 gctttgcatt cccttattta gagtgggatg gaaaataaag gctatgaagg gggaagaatc 254520 tgatcccacc attctccttt ttcattgcag ttttctcctt ttttatggat gcaataagct 254580 gttgcaatct ctcaggatgg aaaagaacat tttaaaacta ctctactgcc agaatgatct 254640 ctttttttta attatactgt aagttctggg atacatgtgc agaacatgca ggtttgttac 254700 ataggtatat acgtgccatg gtggtttgct gcacccacca acccatcatt tacattaggt 254760 atttctccta aatgctatcc ttcgcctagc ccctcacccc ttgacaggtc ccagtgtgtg 254820 atgtttccct ccctgtgtcc atgtgttctc attattcaac tcccccttat gagtgagaac 254880 atgtggtgtt tggttttctc ttcctgagtt agtttgctga gaatgatggt ttccaacttc 254940 atccatgtcc ctgcaaagga catgagctca tcctttttta tagctgcata gtattccatt 255000 gtgtatatgt gccacatttt ctttatccag tctgtcattg atgggcattt gggttggttc 255060 caagtctttg ctattgtgaa tagtgccaca ataaacatac gtgttcatgt gtctttatag 255120 tagaatgatt tataatcctt tgggtatata cccagtaatg ggattgctgg gtcaaatggt 255180 atttctggtt ctagatcctt gaagaatcac cacgctgtct tccacaatgg ttgactaatt 255240 tacactccca ccaacagtgt aaaggcattc ctatttctcc acatcctctc cagcatctgt 255300 tgtttcctga ctttttaatg attgccattc taactggcat aagatggtat gtcgttctgg 255360 ttttgatttg catttctcta atgatcaggg atgatcagct ttttttcata tgtttgttgg 255420 cctcacaaat gtcttctttt gagaagtgtc tgttcatatc cttcgcccac tttttgatgg 255480 ggttgttttt ttttcttgta aatttgttta agtaccaaaa acagatacat agactgatgg 255540 aacagaacag aggcctcaga aataacacca cacacctaca accatctgat ctttgacaaa 255600 ccggacaaaa acaagaaatg gggaaaggat tccctattta ataaatggtg ttgggaaaac 255660 tgactagcca tatgcagaaa actgaaactg gaccccttcc ttacacctta cacaaaaatt 255720 aactcaagat ggattaaaga cttaaatgta agacctaaaa ccataaaaac cctagaagaa 255780 aacctaggca gtacaattca ggacacaggc atgggcaaat acttcatgac taaaatacca 255840 aaaagcaatg gcaacaaaag tcaaaattga caaatgggat ctaattaaac taaagagctt 255900 ttgcacagca aaagaaacca tcatcagggt gaacaggcaa cctacagaat gggagaaaat 255960 ttttgcaatc tatccgtctg acaaatggct aatatccaga atgatctcta ttttattttt 256020 tatgacatat taatcatgtt tgttctcttg tgtcctctct ttctttctct cgattttcca 256080 gtggtccatg gtggtctatt tgtagggttc atatttacaa atgggagtca aggtgactcc 256140 actacagtta tgtgaaaaag tttccctgcc atgcctctcc ctacactggg cgagctgatc 256200 tggttccggg tcagtggatg gagcatttcc tctcgcaggc acaccttcag gctggtggga 256260 gcaacttggg ccatggactg gaaccatgtc aatggagaag acttcctctg tgccaggtcc 256320 tggtcagagc tgccgtcttg atttatttgt atccctcttt ccgtctgtgg taaagatctg 256380 gaggttctta agctctctct ggcctcaaaa cccacagcag gaaatttcct cactcagatc 256440 acccacattt ttagcaagca gagcttcagt tttgagtgga gggcaggagt attgggcagt 256500 agggaaggac acagttctct acgccgttct gaatgcagtg cattaataaa ctctcttcac 256560 agttgctcca gggtgctttg cattggtgaa cttctggctt ccaggaagaa cctggttacc 256620 tctgatgtgt tgggttgttg ttccatctac tctaaattct gtgccaatcc atcccatctg 256680 tttcctacca ttggtttatt tttaaaaaat attttatatt tatgtagatt tatgaacttg 256740 attattatac catcattaga gtttgggtcc agagtcaaac ttctataaac ctgtaatcaa 256800 aaattggcct ttattttcat gtagaaggaa gtagcagacc aaaatggagt tctatattcc 256860 atttttctaa atgagccatt gagatgtaga gcaagcaagt gcccttttga gggaatgtgt 256920 gtgtgtgtgt gcacacatgc aagggcattt tcccatgtct cccatccttt aattattcca 256980 gtagacagtg ggccagcagc aggtggtggc ataacttctc catttgcagt gctgtggctg 257040 tggtgggatc tgaacaggag gcaaccttgg caacagtagg aatagaatgt ggagtcagca 257100 ggaagcgctt ttccctccca cttacctgtc ttcttgtagc agacagcagt gcgggcagct 257160 tcggctgact tgcttagcct gtttccattg tgagcataaa caccttagac gttttttcat 257220 ttcaggacac tggagcttga tgaaattaaa ctacactcat tgtctcaggc aaatctccta 257280 atcctattct gtgcttttgt tgttgttgtt gttgttgtta gtggtgtgtt tctctctcca 257340 cttcgctttc cttttaaaac acaacaaatt ttttttttta attttaaatg aacttattca 257400 ttgcctccct atgtgtcccc tcctttctag tgatattgcc gctgttcatt cccagctgtt 257460 cttgattctt gtacaagact ctttgctggg cttctgcctt ctagacgctt caccttcccg 257520 ttatttcttc cctctgcccc cggaaaggcc cttaccatgg ctctgatgat gatgacagct 257580 gacccttttc caaggtggaa tccacgtttg attctctgat cttgtactgg cttagcacag 257640 tgctcggcat tcagtaaata aggttaagga aggccagtga tatagagtag tagaaaacag 257700 cagttaatga aggcttgctt tctgtcacag gttcctctcc tccaggactg cagcatctct 257760 gtctttctgt cgtagcatac aagacagcat ctctgtcttt ctattgcaac ttccaggtga 257820 gaagccctcc cacaagcata tacaaatttt atggaaacag acaaaaattt gtagggaagc 257880 aaatcccttc aaggttgagt ctttctggtc ttctagaagg taagcttggt gatggggcag 257940 tcacagccct agtgcttatg gaacttggcc ctttggggac agatctcagt taactaaaga 258000 aatgctatgg cacagagtac cttgaatctc ctctaattta tgctgtacag ggaattattc 258060 acactttatt gttaataaca cattacatgg gggaacacca gacagctgac caggactcct 258120 gtgcttgaaa gcttctgctc ttcagcaggg cagccagcct cttctcggtt tagcacagag 258180 cttttattct cctcgctctc tctaaactcc tgttcaagac agtttccaat tctgttgaat 258240 tcactcattt acctcatctg tgcctttccc cacctcattc tctccccttc agagtgccca 258300 tttctgtgtt tcaaatccca caaggccaag cttagatgct attatgtcta tgacattctc 258360 cacctctatc ccaataaaaa cctttgattt catcttgctg tttgtatctt tactctgtta 258420 tatttcaccc ataccagagt tgtttgtgga catgcctgat ttccttcagg ctgtaggcat 258480 atttgattca tttttgtact ccatgagtgc ctaacatagc atcttataca ccatagataa 258540 ttaatagatg cctcttggct gcatttgtat taaattttta ccatgtactt gtcctagcta 258600 gcagagactt ggggggaaat aatgatgact gatttttact tatttattta ttttttattc 258660 ccacaggttt ttgaggaaca ggtgatgttt ggttacatga ataagttctt tagtggtgat 258720 ttctgagatt ttggtgcatc catcacacga gcggtgtaca ctgtatctag tttgtaattt 258780 ttttatccct cactcctttc cctccctttc tcccgagtcc ccaaagtcca ttgtatcatt 258840 cttatgcctt tacataccca tagcttagct cccacttatg agtgagaata tatgatgtat 258900 ggtttttcat tcccgagtta cttcactttg aatagtggtc tccaattcca tccagaaccc 258960 tcaaaaccat gcaaaaccgt ggaaacaaaa tagcctgctc ctgaatgatc attaagtcaa 259020 caatgaaatc aagagagaaa tttaaaaatt ctttgagctg aatgataata gcgatacaac 259080 ttaccaaaac ctctgggata cagcaaaagc agtgtcaaga ggaaagttca tagcattaaa 259140 tacctacatc aaaaagtctg aaagagcaca aataggcaat ctaaggtcac acctcagaga 259200 actagggaaa caagaacaaa tcaaacccaa acccagcaga aggaaagaaa taacgaagat 259260 cagagcagaa ctaaatgaaa ttgaaacaaa caacaacaat aaaaaagata aatgaaacaa 259320 aaggctgttt ttttgaaaag ataaataaaa tggatataac actagtgaga ttaaccagga 259380 agagagagga tccaaataag ctcaattaga aacgaaacag gagctattat aatcaatacc 259440 acagaaatac aaaagatatt ggaagctact atgaacatct ttacacacat aaactagaaa 259500 acttaaagga gatggataaa ttcctggaaa tatacaaccc tcctaggtta agccagaaag 259560 aattagaaac tctaaacaga ccaatagcaa gcagcgagat tgaaatgata ataaaaaaaa 259620 ttgccaacaa aaaaagtcca ggaccacaca gattcacagc taaattgtat cagacattca 259680 aagaaaaatt gataccaatc ctactgaaac tattccacaa gacagagaaa gagggaatcc 259740 tccctaaatc attttatgaa gccagtatca ccctaatacc aaaaccagga aaggacataa 259800 caaaaaagaa aactacagcc caatatccct gataaatata gatgcaaaaa tccttaacaa 259860 aatactagct aagtgaatcc aacagcatat cagaaagata atcaactatg atcaggtggg 259920 tttcatacca gggatgcagg gatggtttaa cattcacaag tcaataaatg tgatacacca 259980 catgaataga attaaaaaca aaaatcacat gagcatctca atagatgcag aaaaagcatt 260040 tgacaaaacc tagcatccaa ttatgacaat ttttaaatat ggggaatggt cttcatggaa 260100 aagtagatgt taatggcacc tgtattaggg ttctctagag ggacagaact aataggatag 260160 atgtatatat aaaggggagt ttattaagaa gtattgactc acacgatcac aaggttgggt 260220 tccgcaatag gccgtctgca agctgaagag caaggaagcc agtccaagtc ccaaaacctc 260280 aaaagcaggg aagccaaaag tgcagccttc agtctgtggt tgaaggtata agagtcccaa 260340 agctgaagaa cttcacgtca gaaattcgag ggcaggaagc atccagcatg ggagaaagat 260400 gtaggccaga agactaaacc agtctagtct ttccatgttc ttctgcctgc ttttattctg 260460 gccatgctgg cagctgatta gatggtgccc acccagattg agggcgggtc tgcctttccc 260520 agctcactga ctcaaatgtt aatctccttt ggcaacatcc tcacagatac acccaggagc 260580 aatactttgc atccttcaat ccaatcaagt tgacattaca tattaatcat cacagcaacc 260640 aaaagattat ctcatttaat ccttacaata gctctgtgta gtgggtatat attttccttt 260700 tgctgaagag gaagtaggct tagaggggtt gagtaatttg cccagaatac ctaggtagta 260760 gaagatagta gagccattat attctgtctg cattcaagag tgtgctgctt tatttgttcc 260820 tgaattgcac acaagctaaa gaatacaact ggatgttcag tctactccta ttttgataac 260880 ttggctaact ttactgcaga gtctgcagag gtgaccaatt ttactctggg agataccagg 260940 gaatccgcca tgtaattcct caggctgagt gttttggaaa cacaaagctg tcactgctat 261000 taagtgatgt tttttcctga gagtctacta tgctcccagt accagcctcc gcaggccctc 261060 tgtctacccc ttttctgtcc tgatgtgttc tagcaggcac tgagaaagtc attgtagaag 261120 ttaccatgac tttccaaatg cttccagaag cagaacacaa tttcacagga gggccaataa 261180 gtatgaatgc caccttgata gaaagtgaag ttttgcgtcc tgttgaacac tcagtaaatg 261240 cttcctgaat agatgcagga ttggcaaaac atagctcccc agctttcata attcagactc 261300 agaggccctt cgtgctcctg ttattcttgt tacttcatgt caggtaccta aaagggttgt 261360 ttttcagttt tcgtcattga tttaaagcag aggttagtaa actttttctg taaaggccag 261420 gtagttagta ttttagcctt tgtgagtatt tggtctcaca aaagcagcca tagatgatat 261480 gtaaatgaat gtgcatggct gtgttctgat aaaactttat ttaaaaatga ggggtcatct 261540 gggctgtggt ttttcaaccc ctgatttaaa acaaaaacaa aatgtgctat gcctgttaga 261600 tgctactaca tttgattctg tgttttccat atttttctaa aatgtactga acaggaaatg 261660 aacaaactga tgacacaatg atctaattta atcattgaga taagagtggc gccaactctt 261720 attgagtatt tgttatgtgt caggcacttg gctaagcact ttacatgttt tctatgattt 261780 ataaagcaaa tattgttatt atcttcattt tttgctgagg gaaggaataa agtcacagcc 261840 agcttacaga ggctgccgga ggtcacacat caccagtaca ctgaaacacg tggtctgatt 261900 acaggatcca tgatctcctg tacagatcat agtgatattg acctgagagg aaagagccta 261960 ggacttacaa tcagaaatct gggttcacat ttcaactccg ttccatgcca aattacatta 262020 aaactgggcc tcagctttcc cacctgtgaa agaggaataa tactaggact tgccctccca 262080 accttagaga ttgctgtgag gataaaagcc tatatgaatg tgctttataa actataaaca 262140 ccatacaaat gtttgttata agtctgccat ttgaatacat cttagtcttt ttttcctatg 262200 tgaaataaaa cattttaaga caagcaatga aattcttgaa actataacag gtttttaagg 262260 gtgttgatcc ccaaagccgt cttcactatt ttgctccctc tctgactcgc tctgtctctg 262320 cctagcagcg ctagtctttt ctacgtgttt gatctgttgt tcctgtgttt aggcccatcc 262380 ctactacaca gcggaagtca gctatttttt ctctttcctt tgctctgctg agcaagatta 262440 aactcttttc acctggactt ttcctagatt actcaggctg ggtggaaatg gggtagctgt 262500 gaggctggga tgttactgta caattcaaat ttatgatctg aacttaacta gatcttgctg 262560 aagattgacc tggctagcac agttttgagg cacctatctt tcagtccctt ctgtcctctt 262620 ggcctggcca ctggccacat gttagtagct tacttctaag gatggaatgc catgcatctc 262680 ctacaaggtt gtctctatgc ttcacacaaa gtaaaagaat ggaggcaact ttgaatgctg 262740 ctcattttca ctcaggcaat ccctttacaa tattgtgctt agtaaactcc ccccactctt 262800 tttttccctt agcttgtttt ttttttctaa taaaagtcta tatcaatttg atgtattagt 262860 tagggttctc tggagaaaca gaaccagtag gatcaattga ttggtcaatc aatcaatcaa 262920 gacaaaaaga gattcatctg gaaggagttg attcatgcca ttgcggtcat tggctagtct 262980 gaaatctgta aggcaggctg gctgactgga agctcaggcg ggatttctct gctgcagtct 263040 caaggcagaa ttccgtcctc ttggggaaac ctcagtcttt gctcttaaag ctttcaattg 263100 attggatgag gcctacacac attatggaga ataatctgtt ttacttaaag tctactgatt 263160 gtaaacatta attatattta aaaagtactt tcacagcaac atttagacta gtgtttgacc 263220 aacaactggg caccacggtc aagccaagtt ggcatataga attagccagc aaacttggta 263280 ttcacaatct gtcattatag tcttatctat aaacctaagg tttagagaaa cgctggtcat 263340 tctgaacaat tccctgtgaa tgcagagatc aaggagcctc cccttaactg ggtaggcagt 263400 gtgaaatacc tgcagtgtac ttgaccttac tgttcaccca ctggcagctg ttcctacagc 263460 ttggcttcag atatataata ttacattggc taacttcaaa gagcattgtt ttccaaggat 263520 agagatggtg atggtgtata ttacttttac cagccccaga cctgtaagag gttctcatct 263580 cttttgttta agattttgtt gttttttttt aatgctcaat aaaagaagct ttattctttc 263640 attaaaaaac aaatctcaga agaacaggga agaagagggt agcctatgaa agtgtgattg 263700 ttatttgata ccatcgtgac ttagcttgtt ttcacctaag actctgagat tctattctgt 263760 ttatgtgaga tttgggctga gttcaactac tatccatatt aactgaatca taaaacaatt 263820 aatccatcat ctggttacat tttggtgggg agggagcatt taacacaaca ctaagccaca 263880 tatttcacta tttttttttt ttgcagcaaa ttgacttaac tgcttgcttt cacaccatgc 263940 ctataaaacc tttttggttt tagaggttct atgtgtctgg aaagtacagt gaagtatctc 264000 atcagaatag tattaatatt tcttatgaca tttcatatgt cctgatatgg gttaatggag 264060 aaatatcata agagtagtaa ttctcttgct gttattattt gtcctattta gacaaacaga 264120 acatagaatt aataagaatt caaaaacttt aatcactgat agagattaaa tgatgtttat 264180 attagtcatc atcacctaat atcttaaata tttaaccttt tatgcagtgt ttgcctctct 264240 acttgggtat gcccttaaca gtaaaaagtg ttgataatgc tctccctttt ggcactcaca 264300 gaattgctat acatatatat gtataaaata tatgtaaata taaaaataca tagttaaaaa 264360 aataaatcta ccactaaata tagtaaggga gttttaaact gaggtttttg aagtctttaa 264420 gaatttattt agagacttct tttgttggaa gtatggtggc tagatgccat gaaaaaccca 264480 ctgaaaacaa gtgtaagtgc taggtaatat gttgaaacat atcttttgaa atgtattact 264540 gagctggcaa gaaagtatgc cattgtagag agtgaaaata agtgaaggca gaatcctggg 264600 aggtaagcca gcctgaagat attgatgaca ctggatggcc ttaagtttcc attttgactg 264660 gcatgtaatc cagccaaaga ttcccacaga aatccgaggt tccaaatggt aaatccgtgg 264720 tgacattggg gtgaccgaga aatgaactct gtgcagaaag gaatggtaac aacacttgtc 264780 tcgtacaact ttggctctgg gtaggggaaa ggaaaacagc ttcctagaga aatgttaacc 264840 acaagctagc cctcatgaga gatttcagct aggatggatg ctatctgtgt agtgcaaaaa 264900 aaaaaaaaaa aaatccatag ccagattttg tgctttaatg tggacctagg tcaatagtga 264960 ctgcaaagcc agaagcagtg gctcacccct gtaatcccag cactttggga ggccgaagga 265020 ggtggatcgc ttgaggtcag gagttcgaga ccagcctggc caacatggtg aaaccctata 265080 tctactaaaa atacaaaaat gagcctagag tggtggtggg tgcctgtatt cccagctact 265140 tgggaggctg aggcacaaga attgcttgaa cccaggaggc ggaggttgca gtgagccaaa 265200 atcgcaccac tgcattctag cctgggcaac agagtgagac accatctcaa aaataataat 265260 aataaaaaaa agtgactgca ggggactggg aagaggaaac acaaatcttt actggggaat 265320 ggaatttcaa gtgtatgcac caacccttag aaatcacaaa acatctgacc cttctgaaaa 265380 taaccaccat gagtgagaca gcaggaaaaa aaaaaagaaa aaaaaaaaaa aaacaaggaa 265440 agagagggac aatagaatca gactcatacc tacaaaactt aaaaattaaa taaaatgaat 265500 cagactcaga ggcttcagag tttgatttaa atacattata caaaagttct gtgtgaaata 265560 tgtttaagat gtagaagggt gcttgaaatg cacaaagtca acagctgaaa aattgaccaa 265620 gcagatatga aaataaaatc caatagaggg catctggaaa taaaaaagta taataattat 265680 agtgaaaaaa gttattagat gggttaatta gtagaatgga tatagcagaa gaaagattta 265740 gtcaactgaa aaatatatcc aaagaatagg tccagaatta agcttaggga gataaagaga 265800 tggtcaatac gaacattagg agacatggag aacagtgtac gaaggtgtaa taaattctaa 265860 ctggagttaa agaggagata gtaaagagga agaaaaaaca caaaactcaa aaaatgtagt 265920 ggctgagaat cttccagaag tattgaaaga caccaatcca cagattcaga aacctacaat 265980 ttgcaagaaa aagtaaaaag aatttcacac caagatccat cttcatggac tggcagagca 266040 taagagatga agagcttatc ttgaaaatgc agccagagag aaaaggtcta tcgcagttaa 266100 aggaagaggc aagcagatga ctgagttctc aatgccaact gaaaatgaga agccagtggc 266160 acaccttcaa tatgttggga gaatataatt ttcaacttaa aatagtgtac attgtaaaat 266220 tacatttcaa aaaaagaggg tagtataatg acattatcaa ataaaaacca tcccttataa 266280 caaatatcac taaagaaact gttggaggat gtagtttagg tttctagaaa ggatgtctga 266340 tatgcaagaa agaatggtaa gtcaaatatt gagaaatatg tgaggaaata gaaacaagaa 266400 taactaatga atcaatgata ctgtctaatt tgaaggttaa atgattaggt agaactaaaa 266460 tatgaaacaa taatagtatg taagtcggga ggaggaggat gaagcttgaa gtgctctatg 266520 catcttgcat ctctggtgtc tttcttgtgt ccaaactttt tcttctttca aggacaccag 266580 ttagactaga ttagggtcca cctaatgacc tcattttaac ttatttgcct ctttaaaggt 266640 tctatctcca aatacggtcc cattttgagg cactaggggt tagggtttca acgtataaat 266700 tttgggggga cacattccag ccgatagcaa ttataaatac aacttttata gtaaaagccc 266760 atcttctaga acaggtagag aacaaggtta cttatttttt ttaagaacaa aattggttta 266820 aattatccta aaatgatttt aggagaaaat ggacattaaa tatacaacat ttcctccttt 266880 attattttat tgatgacttg atatgttttt taaaactcag taaaataaat gattagtctc 266940 ataatcataa gagagttatg cccttatttt aatgccataa aactgtgact tctgaagaaa 267000 tacaatcata taaaatcata ttttaattta cttttgagaa tgtacagtaa ctcaggaagg 267060 cagagtgtgg aacctgcttt aatgaataga taagaatgac tagcaattaa aaattaatta 267120 tctataattc ttctgaagtt cttgaaaata atctcttcta acctgggtaa atattcctcc 267180 ttttcagaaa tgtttgcaat gttgcttttt tttaaattaa tctctttttc ttagataatg 267240 gaacataaat cttaggcaca tttgctttgt aaataccaaa ttgcacacag attaaaattt 267300 aatgagcttt tactgctgta atctcaacaa gcagagtctt tgctgttggt ttttcaataa 267360 gaaatacttt attttgttat acagtggtca ttaagaacct taaagataat caggacagat 267420 tttccaaatt gcataatgct attgcctagc tatttgcatg tatttttttt aaatgacaag 267480 acatttcgtt aaatatttac ttgcctgacg ttgaaagatt tagacaaaca atgtacttct 267540 agttgtcact ttttcaaaaa gattcttagg gaaaagttag ccgttttgtt ggttggtaag 267600 tgatgggttt tcttggaacg tgttgcttgc taattttacc agagaagaaa ataaattcaa 267660 atggtaagct acattccaat ttgtattctt cttctaaagt cctccctgtt tgcattctcg 267720 gattttgaca ctcctacaca ccagttaaag cacttgttag agtgtccaaa aaattgttgc 267780 aattaatttc ccagtctctt ctctctttga tgtgtcacta taatgctttg agtaattttc 267840 agtgtctggc atctgttcaa ggacaatttc tggattttag gagggggaga agcaataaag 267900 gaaacaacat atgttttttc ctaaatagga ggcatttttt gtttgtttgt ttgaacaaaa 267960 atcaaaaact ttcttttcta tataggtgac aaaaagatac acgactcatt ggttgttaac 268020 taccattgca ttcttttctc tttggagtag cccttaagga ccagattaga ccagccatct 268080 gcatcatgta gcatgtctgg gttacctttc ccaaaagaag ttcagataga tgaactttgc 268140 aaaccagagc catctgaagt ttgttttttc tttttgagac agagtctcat tctgttgccc 268200 aggctggagt gctgtggtgc aatctcagct caatgcaacc tccgcctccc gggttcaagc 268260 gattctcctg cctcaacctc ccaagcagct gggactacag gcacgtgcca ccacgtccag 268320 ctaatttttg tatttttagt agagacaggg tttcagcata ttggccaggc tggtctcaaa 268380 ctcctgacct tgtggtccac ccgttttggc ctctcaaagt gctgggatta taggcataag 268440 ccaccacgcc cagtccatct gaagttttaa aatggctgca ggtatcttag taggagacta 268500 attttatttt ccaatgatta gaaaaaaatg accagaccaa gaactctagg gttatgtttc 268560 atctcatatc ctgtgcagga tgttctgaga agtttctatt tgtatctgtg gagtggttct 268620 agtcttgttc atcttgcatt ttaaggtttg gaggtatttt atcttgcctt gcttctttac 268680 caccttgctt taatttcccc ctatattgcc atttctaaag taatgactca ttttcaaggg 268740 tgggtctgaa aggaaagaaa taataaaacc agagatctgg agaagtttct cgttcatggt 268800 cttattcact ttttaataag agcatctaga acagtgagtg gtgccccagc agatatctgg 268860 aaatttttgt ggaattgaat tgaatttgtt cttagagtaa atgacaataa agaaaatagt 268920 attatggaaa ctttcgaccc aagggaaata tcaaggctaa agttgctata ttatttttct 268980 tctgatggat gctgagtttt tctccttaaa aaacaaatcc acatttaaac ataaggcatt 269040 gtttgatggc ctatcacatt cagtagaatg gatttgagaa atacgtgtag gatgcctatt 269100 aaaaactctg ttttgaaatt aaacctaaga ctataagatt gtctgtttaa aaaaattatt 269160 gctgctgtaa tttgagcaaa tctgaactat attgaacttt agaaattcaa atgtatgcaa 269220 tcttgtaata taacttactc catcggtaga catagttctt tgtcccacct ggcttccagc 269280 agtttgtctg tctgtcatta ggctaaactc ttcatgttcc taaacatgtt ttcctcaaaa 269340 ggggacatat ttcttgggtc agatgtaaac atcaagctaa ggagttctgc tgtgcgtcta 269400 gacaaataag gttcattttc atcctctaca tagtgttaaa cttgaattta agatcacaca 269460 gattccttta cacgttacca atgtaatgat atagacaatc tcactttatt cattcactct 269520 gtttaattca ttcaataaaa acgtatacat tggctgccta ctgtgtgcca gttggtgaag 269580 atataaagat gattaaggca agggtctgtg ctgacatgcc taatgggcag gctgacacac 269640 ctaaacgcca gggaaaaaga gggatgagac ctgggcctct gaagccctgg ccacctggct 269700 cgaagctcac tttaatgtgc ttctgggtgt attccatgac tttttaaagg cgcttatgtt 269760 tcctttctgg taaagcatgt ttaacatgca aaatgcttat ttcattgagt agcttttaaa 269820 aagtgttcat agaatgtcta gaacagtgct tgtctaatag aagtataatt caggtcacgt 269880 aggtaatatt aaattttcta gtagccacat taaaaagtaa aaagcaacag gcaaagttaa 269940 tatttttttt tttcctgaga tggagtcttg ctttgtcacc caggctggaa tgcagtggtg 270000 tgatctcggc tcactgcaag ctccgcctcc cgggttcaag ccagtctcct gcctcagcct 270060 cctgagtagc tgggactata ggcgcccgcc accacacctg gctaattttt tgtattttta 270120 gtagagacgg ggtttcaccg tgttatccag gatggtcgtt aattttaata atatattcat 270180 taattttaat aatatattca tttagtccta tataaaaaaa ttagcatttc aacatgtaat 270240 caatagaata tattattagt caactatttt gcattctttg ttttgtacca tctttgaatt 270300 tcaatttgta ttttatactt acagtgcatc tcaattttaa tgctaaatgt catcggagat 270360 attcgatctc tgtttagctt taatatattt ttgggttgaa aaagtaaatt cacataacca 270420 agttcttcca aatatacttg aaagtgtttc tgataactga gttatcaact taaaaatgta 270480 agttaatgac aataaatgaa agaaaaattc tgttccttag ctgcactgac cacattttag 270540 tgttcaatag tcgcaggtgg ccagtggcta tcatattgga tagtacagct ttagaatgac 270600 agttcagtgc aacaagtgct ataatagact catgaactgg aagctccggg aagttaagaa 270660 tgggatcaat gaagtgggtc ttgaaaaacc aataaaaatt caccacgtag agaggaggag 270720 ggcgactact ccaattcaat cttttgaaag catgtgaagg agcaacagta gacttcttta 270780 attatttaat agtaatttat tgaacatgaa ttatgggagg tgcatggtgt gggtgctggt 270840 gagacatagt tcctgagctc aagtagcttg gtgtctaaat attcatgggc ccatttttca 270900 gaaaggatgg atatatgtgt gatcctgggt gtgccaaatg ctgtggcttc ctgaagctta 270960 gatttccagc ttgtcacctt caaggttacc ttgtgaatag gacttttttg agctgtaagt 271020 aaatttactt tgcctattta tttccaatgg aaaaaaagct tttttaaaaa ataaatctca 271080 tcttattgcc tatgattggc caagacaaca tggcccatac agaaggtttt tgatggcttc 271140 tgaggtctgt tatcatttgc ttattggcat ttcagctgtc aaccagggtt ctgtcaaatt 271200 ccattcctgc ctttagctct tttacttgaa tacctggggc aatggcagaa gtggttgcta 271260 tttgtcacct ttccaggatg ttagtcgtgt ccttgagaca aatagaaaat ttaaagtcag 271320 atgacttgat tcctctgcca gttaagaccc ttagagagtc ctcagaatgt tgcttatttt 271380 taaatttcaa gtccctggta aggatcaagt aaactcccca atttgcagat ttctatccag 271440 ttgactatgg attttgcctg ttgctttgtt tccaccaact ctccctgaag atgaggcgca 271500 cagacagaca actcacaggc aagaacagcc tggtccatct tgaaagattc tcaagactat 271560 tctccacaag ataattgtct acttttaaaa atattcagta aagggaattt ttgctgttat 271620 ccttggttgt gtttttagta tctcatcatc cttctagttg taggaggctt ttcctaacat 271680 ctaacccata tgtctgttgt ctcatcaggt gtttctatta aggctacttc cccatcaatc 271740 ttaatttttt ttttaatctt ctgagatgta taggttaagt tgaaatcaga gactttcata 271800 aaatggtaag atggccattt aaacgcaact atgaggaaat aatgtaagca ggattccatt 271860 ggagaaccaa acactagcaa caactaactt ggtaatcaat gttgggactt gaagttaggc 271920 taaaatcaat agtaatggca ctcgtatgta caaatgcaga actttttaca cacaatgatt 271980 tttccctctg ttattataca ctagctgtgt ctgagtagac agtccagctc cactacctgc 272040 agtccaccct gggctgtgta atctgagcac tgatgggctg ttatttgtac gtattacttc 272100 tatgacactg ttttttcatc tgtgttagaa atgtctttct ttcttgaata agctgcttca 272160 atttcttata gacagattct gcttttatga cccttgtttc tacaaagtaa tctctactca 272220 tgctgaaatc tcagacaatt ttaacaaata tttagagtac ttaatttttc tttgaattct 272280 aaatattatc cttctttagt tcaccatagt tggatatttt gagataactg tggaggaaac 272340 agcactgatc ctggggccat gaaacctgat ttcaagatct agtcccttct ttaattttgc 272400 acaactaatt taatcacatt catccttaat ttcatcatca ttaaaatagc agagaataat 272460 tcccgtttca tggagttgat atgcaatgaa atagcatatc aatgtatgta tgaatgtccc 272520 ccaacataga gtactacaca aatgaaacgt gtcactcagc ataacgttat gtgctccttc 272580 ctgcaactgg attgcactcc agtgggattt catgctggtg agatggctgt gctgctggac 272640 ttcatgggac accaatcttt gaaaataagc ctgatctggc tgggcgtggt ggcttatgcc 272700 tgtaatccca gcactgtggg aggctgagac gggcggatca cctgaagtca ggagtttgag 272760 accagcctgg ccaacatggt gaaatcctat ctctactaaa aatacaaaaa aattagctgg 272820 gcatggtggc atgtgcctgt aatcccagct acttgggagg ctgaggcagg agaatcactt 272880 gaacccagga gatgaagact gtagtgagcc gagattgcgc cactgcactc tagctggggc 272940 aacagagtga gactctgtct caaaaaaaaa aaaaaaaaaa aaaaaaacac aaacaaaaaa 273000 aaaaaagaaa aagaaaataa acctgatcta tagatgaggc cagtggatct tgtgaagagt 273060 tgaaaggtca ggtatcagtc ttataccatg tcggatgggg caatcgtcat aactttttaa 273120 aaaattattt atttattttg agacagtgtc tcacgctgtc ccccaggctg gagtgcagtg 273180 gcatgttttc ggctcactgc aacctccgcc tcctgcgttc aagcgattct catgcctcgg 273240 cctccctagt aactggatta caggtgtgtg ccaccatccc tggctaattt tttgtatttt 273300 tagtatagac agggtttcac cacgttggcc caggctggtc tcgaactcct gacctcaggt 273360 gatccacctg cctcagcctc ccaaagtgct gggattacag gtgtgagcca ccgtgcctgc 273420 cccaattgtt acagcttttt aagtggatta tatgcctgct tcaggcatta gacataataa 273480 gttaatctgt tgataagttt cttcatttct taattttcag ttgtgttttg atgtgtgtgg 273540 tctgggtgag cggctcagtg ctgctgctgt ggagaaggcg tgatatggaa gggatgtgac 273600 tgtccttctt catcttcata acggggccag gactggggtg aggtgtgtga gatgaatgaa 273660 gcactggttt tgatacaaaa tttaagaaaa atcaaattca agaggtaata ttttaatacg 273720 atatttgtaa aaaatcaaaa ttagtgcaaa aatttgtgat gagcaaaatg ttagataaag 273780 gcattgttgc ttttcttttt ctgtgtattg taacacacca tcacttagtg gagaaacagc 273840 tctcactttc ctcctcccca gatacaacca tttatgttga attaaacttc tagttctcct 273900 atacctgtga gcatccccca ggccccttgg tatggagaaa gcagtttatt tgtcttagta 273960 agattataaa agtggcaata aaatgtgaat gtaatgaaca aaatgcacat tttgtggacc 274020 aacttgttgt tttagatcta tttttgaaaa ctcattaggt atgtgcatga ggcaaaataa 274080 ttcaagtgca gttggatatt aaatgaaaaa gtgtcaggtc cccttttctg ccatattctc 274140 ttctgtgtct tcattagtgg aaaccatttt gaccagttct tataattcta atgatttgct 274200 gatggctcta attcttggtt tatcaacttc aagcagaatg tcttgacatc ttggtatgaa 274260 agttaaagaa tatgaatcat ttgttctctc ccttctcctt tcctctttct ctgcctctca 274320 gtttttgttg tatgctcacg gagtatgtgt gtgagcatgt gtgtgtgtgt gtgtgcacgc 274380 gagcacgtgt gtgtgtgtgc gcgcccatgg gtccattttt gcatggcagg ctttgtttta 274440 gaaagattgg ttacaacagc tgccccacca atctcctcta cagggaagga ttcctactct 274500 gagaccttgg tcttttccag gcagatcact tacatttcct cacagattat ttctcatcct 274560 gcagcctggg tccaaatggg ctttgctgtg aacagtgact ctcaggcttc tggtctctgc 274620 tgtgcttgag tgtcgttgag atgctccatc tcctcctact gcacccaccc agcaatcatc 274680 tctctttcag gaattcacca aagtcttttt taaaattatt cttttgtttt gagacagagt 274740 cttgctctgt tgcccaggct ggagtacagt ggcgcaatct ccgctcgctg caacctctgc 274800 ctcctgggtt caagtgattc tcctgcctca gcctcctgac tggcagggac tacaggcatg 274860 tgtcaccaca cccagctaat ttttgtattt ttagtagaga tggtgtttca ccatattggc 274920 caggctggtc tcaaactcct gacctcaggt gatctgccgg ggtccatttt acgtggcaga 274980 ctttatttta gaaagatagg ttacgacagt tgctccaccc atcccccctg cagggaagga 275040 gtcctactct gagaccttgg tcttttccag gcagatcact tacctttcct cacagattat 275100 ttctcatcct gcagcctggg tccaaagtgc tgggattaca agcgtaagcc accacatccg 275160 gctcaccaaa gtctttgggt ggttgatgtc atatgcctcc agttgatagc acttttaaga 275220 atttttcctt tttgtatgct gttattattt ttagaaggct tttggattat tattgttaaa 275280 gagtatgcca tgtctatctt ttaactttta agcatctatt gctttgttac ttgtacttta 275340 tatatatgta tatccttccc ccaataagac aaagagtgca aataatcacc tcccttgcct 275400 gttgtttggg tttaattcag gagtcagtgg aattaaaagc ctaaactcag tatagtttta 275460 aagcagcagt ccccaaccct tttggcacca gggactggct ttgtggaaga cagtttttcc 275520 atggaccagt gtgggggctg gaaggtgatt ccaggatgat tcaggtacat tacattaatt 275580 gtgcacttta tttctattat tattacattg caatacataa ggaagtaatt atacaactta 275640 ccataacata gaatcaatgg gagccttgag cttcttttcc tgcaactaga cggtcccatc 275700 tgggggtgat gggagacagt gacagattat caggcattag attatcataa ggagtgcaca 275760 acctagatcc cttgtgtgca cagttcacag taggattcgt gctcctatga gaatctaatg 275820 ctgccactga tctgacagga ggtggagctc aggcagtaat gcgagcaatg ggagtggctg 275880 taaatacaga tgaagcttca cttgcacgtt cactgctcac ctcctgttgg gcggcccagt 275940 tcctaaccag ggttggggac ccctgcttta aagaatatgt ttgtggattc atagagggaa 276000 acaacacaca ctggggcctt tcggagggtg gagggtggga ggaggcagat gatcagaaaa 276060 aatattaata actaatgtgt actaggctta atatctgggt gttgaaataa tctatacaac 276120 aaacccccat gacacaagtt tacctatgtg agaaacctgc acgtgtactc cagagcttaa 276180 aataaatgtt aaaaaattcc ctccaaaaag gatatatttg catcggagtt atatttgtat 276240 atgagtatat atttgtatat ataaatatac ttgtatatga aaaaaatatc ttttttcttt 276300 cattttattt tccaaacatt aaagtcgggc acattggtta ggaatttcac caatactttt 276360 tacaaaactg aggacttgga tgataaaggc actttttaaa agattacaca ctggcatggg 276420 gaataatacc tttataaaga tgatctatgt gttcctgaat atcccgatgc atctcctagc 276480 tggatcttcc gctccacaaa aattcataag atgagattct tgaattagaa tgcatgcctt 276540 aatgtattaa gtctatgtag agagagttat ttagtccatg taaattaagt gggaatattt 276600 ttatttgatt actgttttat ctggatcttg cccacttaag gccttcaaaa atgaaattta 276660 aggcctgtta agcagaccca acatcaacag catattctct ctctcttgta agtattgtct 276720 agttgataaa aaatttcaaa aacatgtctt aatcaaaaac aagatgatcc agcacaggtt 276780 taataaatgt tttgtgaata tggcacattc gtgtctcatt actacagttt tcctatgctg 276840 tctttctcaa taattccccc caaaattgta gtgtttacat tatggcattt atagttacct 276900 ctgaacctaa aaaattaact tcaaaagtat ttaaaaaaat cattatattt aaaaccattt 276960 catgtttaaa tggtttgtac agggcaatga aaggaaatgt agtaataaac acagaatcag 277020 atttggtcac taatattttt ctgcagttga aatatatgta gactggctta gggtctaaat 277080 agcattgaat cctgttacct tccatctata atcaattaat gtattatgac attgttgtcc 277140 tcagatcact gggatctcat ggtaagtaag taaagggatt attctgtgca ttttcccaat 277200 atctatatta gttttaatat acctttatgt taatgtatga cactgacact tagtaattgg 277260 attaacttcc tatcagaatt tgtttttcac tcatactttg tatacatgtc ttaagggtag 277320 ggtagatgta catttttttc tgtgttagcc tatctgtttc tgtgacacta catgctttct 277380 gtcctccaat ttgtgtttct ttccgtgtac aaatatgcat catctaccat ctacatctac 277440 aaaacatgta ggcttccaat gttttcatgt aaatacattt catgagtcct cagtagagtg 277500 ttagatgagt ggttaattag taatgttaat aaatgtaaat tacaataaaa acatttataa 277560 tgttaataaa tataagttta ttgaacttaa ataatttaaa catcttctga aatgtagtag 277620 aaattatgat tagccataac tagtacagta ttttttgctt gtttaatttt tttggtgata 277680 ttccatttgt ggaatgagtg tgtgtgtgtg tgtgcagtac agacagaaag gagagaaaca 277740 tatctgcatg ttatgttaga aagagtagtg ttagctaccc taccaaattt acatactggc 277800 tgaacacagt atgtaaaaaa ttattttttt agtccattgc tggtgttcct tgttgttggg 277860 tgactctatt ccacatggtg atgcagggaa ccaatctcct tccttctgtg gctgtgtaat 277920 cccttgcaac cttgaagtcc tctgcatcta actttaggat gaggaaagtg aaggtggagg 277980 atatagccct cttgactgcc ttgacctgga cctggaacat ctcttttgct cccattccat 278040 ggggaagaac tagtgacatg gtggcccata gctgcagagg ggaggctgag aaatgcagcc 278100 tctggataag aagcctactc ccagtggtta ctgtacattg tgggagggaa gcttgaattc 278160 tgatggacag tgagaaccat tctccacaca ataacgaaat gacgtcttct caaccttggc 278220 aatgtagcat cctgtgactt aagtatgtaa ataattatca gtacaggtca gtgaaaaatt 278280 aggtcacctt tcccttccac ttttaattct atagtttaat ttgcctatct gctacatatt 278340 atatatatgg gaatagataa gattatctat aaacatgtat aaatttgttt cctacactaa 278400 aaagaaaaat gacaaagaag aattaagtta gttgcccaaa tccacacaat accaccagga 278460 gaaagtctag gaaccatacc ttctaaatcc aggtctacac ttctttagtg cactaaattt 278520 tttcctaata tagctctgag gagactggtg tttaagagga gaatgttaag ccaaaagccc 278580 atttcacttg gctctgtaca gacagtaagt taatttccag gatgtataac tcctgatttt 278640 ctgtgatgac agagaaaata ctgacctgat ttgggtaact ctgaggtttg gagatcttga 278700 atagcctcat gttcctgaac ttctttacca tacatgaatt acttcttagg aagaaacatt 278760 tattctgtag aatttggttt cgcattttat ttttattttc ttagacactg gtagttggaa 278820 attcaggaag aatttgacta caaaaaacat ttattaaaaa gagtttctaa tctcacctgc 278880 taagtgctac aaggaaaaaa aaaaatacat tttgagccct caaggggctc caaatacggt 278940 tgaaggaaaa ttagacccag aatagtatat gattaggaac aaaacgatgg cagagaaatg 279000 agagtttaga gaaaggagag ataatcctga gttaccttag gaagagaaaa tttcacagag 279060 aaaacggccc ccacactgat ttggggaaga tgattcagac ttgtctcaat ggcatgagga 279120 gcaggggcca gatgggaaag gacatcgtgg tggaaatgac acgatgagca gaagcttaga 279180 agtacttctg cttcacgtct gtgattctgc ctctcccctt gtttctgcag tgctaagttg 279240 agtgtagttc cccacacaaa ccctgagctt tcttcccctc caggctgctc catcagtcag 279300 acaggagtgc cttctcaggg gatcctcttc ctcatcttat cgggccactc atctcgtcgc 279360 agacattccc atactcctgg ttgacttgct cttccctctt tttaactgac atgagcaggc 279420 atcacctctt ccaggaaact tccctgacac caggctgagt ctctctggtg tcggggaagg 279480 cttctgtatt actgcatctg ccattttgat ttaaggtttt ctgctcattc caactcaaca 279540 gtgagctctt tgagggcaga aattgtgtct tattcatttt tcttgttatg ccctaaaaat 279600 gtattgtgat aatatataag taacgtacaa tttaccattt tcacctcttg aagtgtatag 279660 ctcagtggcg ttaagtgcat tcacactgtt gtgcaaccat tatcaccatt catctccaga 279720 actttctcat catcccaggc aaactctgta tccattacac aatagctctc catttcctcc 279780 tgccctcagc ctcaggaaac ctcccatcta ctttctcttt ctacgcgttt aactactcat 279840 atagatggaa tcatccaaca tttttccttt tgtgcctggc ttatttcact tgacataatg 279900 ttttcaaggt tcttttatgt tttcttatgc gtttttatat ctctctatct ttgatagcac 279960 ccaatacata gaagacaatg aatgtttttg tgagtgaaaa cataagacca gaaagaaata 280020 ggatgtcata ttctagggac actcaagaca ctttcttgag gacagaggca ctgtagcttg 280080 gaatttggaa gatgaggttg gcaaggtggg tggggaaagg atggaaaagt gatacgtttc 280140 ttgaagcatg tggatttgct tccataagca gtggtggacc agtgggcacc cttatctatt 280200 aaaagaatga ttttttttgt gactcgtgta gagcactgtc ttagttacct accccagtgg 280260 tagataagag aagcggatta aaaagagatc tgaacctgag gaaatggaga ctaccaagtt 280320 ttttgtaaat atgtctgtta taacatatat tatctagtac ttgcgatgcc tgtgccaaag 280380 catgcttttt ggtttagtta agcctactta gctcgctaat ttcagtaatt ttggcttgaa 280440 ttgcaaaaag ttgatggggg agatggggga gtctctgaca tccttccccc actcacaggt 280500 ttgaaaaata aaattatgaa gagcaaaagg atctttttct gtggtaaatt gtacttcatg 280560 acaataaacg agttgtggtt ttagtggtta atttataaat taggccatct ggttcttctg 280620 taatctaaag atttttatat atatgtaaaa tacaaagttg tcctgggcaa ctgccaatct 280680 ataaaggaga aaacatcttg aactctgtgg agataataaa accatattca gctgccaaag 280740 tgctgctgac atactgtcca atgagacacc caacgccttt gcattacagc cagcaaggtg 280800 tggagctaga tgtattgatc tatttaataa tattagcttc tcttctctgg gtcggacttg 280860 gcccagagca agtgaacagg acctatctat ctccttctca aaagtcacag ctttcttacc 280920 aaattgtaca actcaagcca caaagaaaac aagtcaagga aaggaccaga ggagcacgag 280980 ggcacatgcc ttgttcccag accctgggac cagctccagc tctggctcct tgcagatccc 281040 gctcttctca agttctctgg ctttgatcct agttttctgc cctactattc ctgacatgta 281100 cagcacttag caattcataa cttgctttat taaccaatat ctcaacagaa cttttaaaca 281160 acctgggagg aagcagagtg ggtgttactg tcctcattgc acagataatg aaactgaggt 281220 tcagaaaggt tgagtgtctt gcccaaggcc acacggcttc ttagtggaga agccaggatc 281280 tgcaccaatg tcttccattg gacacactgc cacttaatat ggtacttagt ttttctttct 281340 agatgaagca gtatgaggaa ttctaccatg gatatctctc tctatttttt taaactgcaa 281400 aataatgata atgataataa tgaatacttc tagaatacag tctctatgcc aggcactata 281460 tgctttatat gtactaactt gcttaattct cctaacaacc ctagaaggta gttactaata 281520 ttatcactat ttttaaatgg ggaaactgag ttacagagat ggtaaataag ttgcccaagg 281580 tcacagaggc agccagatta gtgacaaaag tttgagagta ctcagtttga attttacatg 281640 ttccgtggat atggtttatg ccaaatacct tctcctttct agacctcagt ttcctcatgt 281700 atcaaacaag tggactgcac tatacaactc tgaggtccct tctagcctga agattagagt 281760 cttttatgcc cacatgatat ggaaaacatt aatgctggct ctttaagact ggaaccttgt 281820 catttaaaaa aataagctct actaaatttg cagtaaactg tccaaatacg atctctggtc 281880 tctgatttgt atctctcaca gagcatgata caatgctaga cacatatata ctcattaaaa 281940 acttgctgaa ttaaattgta aaacattcct ccagatagac cgtaagggtg agctgatgcc 282000 ctaatatgct cctcagctgc tgacttagga cccgtgggtg acaaaccctg tccttgttgt 282060 tccatctgtg acagtgggca gtgtccaaaa tgagtctctt catcaaaagt gagtccagga 282120 aactggatca gagtaagtaa ggagtcttcc ttgcttcttt ttctctaaaa tacaatacag 282180 tgcattctag caaactacca gcatgcctat aaatctcatt ttaaaaatat caggaaatag 282240 atgctcattg ataaagaggg taagaatgag caagggagag agtcaagcct gtacatttgt 282300 gcttagggta ttttcatttg agaaattatc attggaaaga tcaatttcca aggcaggcgt 282360 tttgtcttga cttaataaac taatctttat caataataat taaataatgt cattttccca 282420 gatacaaagg ggaaaccata atgcctttca tatgccttct catatcttca gtgtttctca 282480 aacccagctg tggggtcttt ttagggaaga tacaaggagg gtgagaccat gtggagcaca 282540 cactcagcag ccactgtgaa gtcatgggtc ccttgctacc tttggaagct gacaatctgc 282600 atgaaaagca gcccctagga acatgggtag tggcccggga tccaaaactc ctgaatccat 282660 aaaagggctt ttgacttctt gttccaggac aagtgacatc tgacatgctt gcctgcttgt 282720 ttgcctttct tccttctcct atccgtcttt ccatccatct gtccatcagt ctatctgtcc 282780 atccagtcat ccatccatcc ttccatccat tcgtctattc atccatccgt ccttccatcc 282840 atccatccaa gatttattga gcacttacat gacaggaagt atgagacaca aaagaaaatt 282900 ctacacaatt ctcctaggga catgaactaa tggttagcaa aaatatatgg gaagtcctgc 282960 ttcaagtaaa attatgactt aagatataca tcagatattt gaaaaagata tttttaagtt 283020 caacattgaa attctaacta cattgtgtcc ttaatttcta ttttctagtt agactttttt 283080 gaagatacaa atcatttgaa ttatcattat tattgttact tgattttatt tattccacat 283140 gaatggtaag aattttaaag gaaggtgggt gccctaaaaa tacatttatg ccaactggat 283200 tgaatcacct tgaatcacaa tgagtacaac aactgctaat gagctaacac ttaatgagta 283260 atgaccaggc accagacact gttctagcac tttatactta ctgatttctt tactcttcat 283320 gataacccta tgaggaaagt gcttttttgt taagctccat tttcagctga agaagctgag 283380 gcctggagaa gttacatagc tttctcatgg tgtctccact atgaagtagc tgagctgaga 283440 tctcacccaa ggccctgctg ggttcaggcc acactcttaa gtactcacag ctgcatcaca 283500 ctgaatatca tctccctgca ctgccatttc atttgagcag ggctttgcct gtcaagaaca 283560 ttcatatctt ttgataaaca gtgcattttt tccctgatag tctgtatggg acagcctcct 283620 tgtttgcatc tgaaggacag ggacttcagg acctcctgct gtggtcacca aggaatcaca 283680 ttcaaacttc tcagcaaggt gttatggtcc ttctcagttt gcctacgatc cattgaggca 283740 aaggtttcct tctctcaata caccctctgc tttagccagg gggacctccc actgtcctct 283800 ctatgtgttc tatttgttcc tgactgttag tacccgcttg tgtggtttcc atgatccttc 283860 ttctgcctgg aatgaggctc ctcttgagtc ctgagagctt catttctgtc tgtcttttgg 283920 gctgtgccaa agcccctctg ccttcgtgga ctccccactg attcattacc aattttcctc 283980 tcctctgggc tcttcttaga ttgcaaatgg tgcctctgga ttgggtacca agacttgcag 284040 tgccttattt tgataccact aatatgagac catgttatat gcctcttgag atatcattcc 284100 ctttctagca atagacagtg ataagcatgc gtatagaggg taaacgtagg actttgaggt 284160 tcatccatct caatagacaa aagtaaaagt atgctaattt caatccttca cacagtaaat 284220 tgaatgtaat aggtcttcag taactatttg aggaatgaaa ttgttattga tatattgatt 284280 taactgagca aatccataag tgccacgctt ggagtaaagt acagggaatc tcattttttg 284340 ggtaatttca aacaagtagg agaccatcca ctatctatta aggacaaagg agatttgagt 284400 gacaaacatg ttccagacca tccaatggtg ttattctact acttcatccc agctagtaaa 284460 atggggcaat aagaaccaaa aagcaggtac tgtccctatg taagtagact tcctagtcct 284520 ggccaaaaca aaaacaaaaa aaaaacaaag caacacaaaa caaaaacaat gtgtgaagag 284580 catcttaccg ttcattgctt tggatgattt gtgcaaatct agttaatggg ggtggatctg 284640 atcagtcttt gtaggaagtc agtattggca tatgtctggc ttctgaattt tctaaaaata 284700 taattattta tttttaaatc cattcaatca acactgaatt tactaatcaa ctactaaata 284760 agtaaaagat cctatagtag atccttcaag aaatggaaat tgagacatta ggtcactata 284820 aaccccaacc cttgtaatct ttttgtggca accttaggaa acttggaatg ctttttacac 284880 tctgataaag gtttaattgt aatcatagcc ccagtgttgc aaaatgagtc agaagataca 284940 aagtatctca taggataata ttatagctgt aggtacttca aatggacaag tataacacat 285000 tatgactgct aatatggatg cattgggagg aaaataagcc ctaagaagca atatgcagaa 285060 aagctatgat tgctggagac agatagatcc aagaacctag gtaatttttc agcaaactgt 285120 ggttccactt tcgcctcttt cttgacattg actgtgtttt taacagggaa aaagttatct 285180 gaaatttttg atagagttca aactttaaat cgtgttcact ttgctaaaac tccactggat 285240 ggagtggcag aagagaaaaa acacagaaat aaaagaaaag cagtaatgga gaatggaaaa 285300 tctttaaaga tgctaccatc ctgaaaagat tcgaaagcaa gcccaggaaa gccacgggga 285360 gggaaagagc gcttagaggt gtccccaaag ctttcagaag tgatgaggga aaccccagct 285420 cttcttgtta cttcttggca ttttgttcct ctatacgtta gcttttggtt aatctttcat 285480 gttacttatt atctctgttt taaaatttca cattaactca ttggtttcat atcccactta 285540 acaaattaga tattttcctt gggcttatta agaaaattat ttgctctcat atgttatggc 285600 tttagatttt ctgtgtagct aggactgttc ttaaattttt atctttacct ttgttatttc 285660 tctgaagcat ccccattggg gtggcagtgg ggggtattaa atggttatgt aaaatttaca 285720 tgtaattgtg caatttacac atagcctcaa atataatgag gcctagtcta gctgcccata 285780 ccaagaggat attatagttg ccaataaaat cagtattatt tctttttttt ttctgttctt 285840 ttttagcttc ttgcaaacat tcactcagaa tcctttttga atatcagttt tgtgaaaagc 285900 accgtgctgg gttctttggg aaaagccaag atgagggcaa atgcatcctc cttcctagtg 285960 agtctagcac acagatgact caggaagtca tgcactggag gaggagtatc ttctagaact 286020 ggggaaaggt taaggaaggg atcagaaacc tttttcactc aaccaattac attttcctga 286080 aagcatgtta ttaatcgtac atgatcttgc agaccccaga tagagactat atcactatat 286140 caattgtttt cttgaacaac tggagttaat tctcatatgt ttggttaccc ttcaagtatt 286200 tatgtttagg atctgttttc ttcctcttaa cttacattcc aaagtttagg tatccttccc 286260 ctccatttgc tgtccaaaac agcatccttt catgtagcta catgccattg gaatgatttg 286320 gtttttgcca tggattccta gtcctaaatt tggactttta ttggtatcta agatgtcatg 286380 gacagaaccc acagatgttg tacaaaaagg gctgagtgga cagtccaaca gagttacatc 286440 atctgttcca aacacccttg taatggttgt atcagcgtca atgtctgagt tgctgtcctg 286500 gttctcctgg ccagtcctca gctggccatg cctgttcagg caccagagaa agcttcatac 286560 ctcaggcaaa tctttacaag ggatttgaaa ggcaagaaac atgtattttg gaggttttac 286620 ctgtttattt catgtatagc ttcatattaa cagattttgc tatcacttaa aagtaaataa 286680 aatgattttg atttctcaaa atcatcttat aatttattaa tctattttaa ggcttgcatt 286740 tacatttaat cttcaaatct tgatgcattt tcacagagtt tctttagtta gttaaggata 286800 ttaatgactt cctttaatag ttgatgaagt gagtcatcat cgacagtgag tcactaaggc 286860 caactcttgt acctgctctt aaatagcagt tgttttacta gatttgtact gaaacctttt 286920 taaaaatctg tttgtcttat atataacaag catttccagt agttaataat actttcttag 286980 ctcttcaatc attttatgag agcattacaa gaaaagcagg agatggggaa agagatatct 287040 tgtttgccat gtaggatgca tgaaattctt acttagtctg ttgtgttttg gattcgagag 287100 aaaatatgta atgaatcaaa atgtttccta cagtcctctg aaaagatgta atgagacagt 287160 cttccagcag cctttgatca tctgggaagt cattgacttt gatccttatc ctatcagggg 287220 ctcttaccct ggggtccata aatacccagg catttttaag aagtggattt cagtataact 287280 tgtttcattt tgtgattttt aaaaatattt tgttttatgc acttaaaacc ttaatctgag 287340 aagtcatctg tagactatac cagatttcca aatggaataa aaatatttaa gaactctctt 287400 atgtgtgtgt ttcaacctat aaattttata tgtgtagctc atggttaggt ggtaagtaga 287460 gaatttgcta tctgtgtaat atttggtact ttttataatg aaaaaggaag taatacaatg 287520 ataggtacca tttatttgtt gaccacccat attttccagg gaatgtgata gatacttttt 287580 atatattctt tctagttttc accataacat gctgcaggga tagtgttacc attctcattt 287640 tgcagatgaa gaaattgaaa cccagaacaa ttcgttcatt cattcaaaaa atatccatag 287700 agcatacact aagagaaggc actctgctag gcaccagaaa ttgaataatt gaccccaaat 287760 cacctaactc ataagtggca aagctggacc taacaaagcc cattatccct tctatcacac 287820 attccatcct cataatatca tattctacat agaaaaactt aacagtcctg ttgagacact 287880 tggaactcta agaaggtagt caacagatac ttttctcttt atataaatat gatatctaat 287940 tagcttttcc tggaaaggag tgattctgcc tttttttaat tctagcattc cctgagcaaa 288000 ttagagccca ggtaatgatt tcctgagata agtcaattct cttctaggac aatctctagt 288060 cttgtcatca tgagatggaa taacaacggt ctatgtcatt tcagtgacgg cacctgcatg 288120 tccttgtatc taagaaaaga cacctccttc tctgccttgc taaatatttg taaactttgc 288180 tttaattggt atatgtgcca ctgttttgta tgtgggaggg gtttatggtt ttgttttgtt 288240 ttttggtctt ttttagtaac cccaatccaa actattctca tttgtaacct aaaatactta 288300 gaacaagagg ctttgcaatc ttgaagaccg aatacatttt tactactaaa tgtaaggcag 288360 atttgagcca cccattttgt agtgcttgat tatggcaacc cgaggaaact aatacggtta 288420 ctctttatct ttattaggaa atactgctgt agttcctgtt gtaatcctta gggagccaac 288480 attgttgatg agacctagta ccaagccaga ggccatgttg aactagcaag atatgggata 288540 gtttttactt tcaaagtaat tagcatctag agtctagaga gtttctctta cagggtggcc 288600 tggtgtctta gtctattttc tgttcctata atagaatacc tgagactggg taatgtacaa 288660 attataaaga tttgtttgac tcacaatcct agaggctggg aggttcaaga tcagacagcc 288720 acatctggcc atcctttaat gagggcctca tgctgtgtca taacacagca gagaattgga 288780 aggagaaatg ggcacatgca aagagaaaga aaggggacga aaggggctaa ctcactttgt 288840 aactatgaga ctaatccatt ccctggagaa ctaatttatt ctcatgagaa agacatgaat 288900 acatcttaac atcctaatca cttcttaaag gcctcaactc tgtacactgc tacattgtaa 288960 caggcaatta aatttcagca tgagttttgg tggggacaaa ctacatccca actgtagtac 289020 ctagctaccc actttatttt tagagtggct atttaatgac ctggcaagat ctactgtgct 289080 tgtaaaagaa tccaccatgg gttaaagaaa aatagtttct ggcttccagt ctccttttgg 289140 cctctctcta gaatggcata tacaagttca gtggttactg acttcaaagg tggggtggaa 289200 gacactgaaa tgaatttttc tcctttcttt ggttggttgc tctctctctt tgttgctgaa 289260 atttgtgtag gataatggaa tgaatatggg agatagggaa ctatagaaag actggaggga 289320 agggagaagt cttttctgaa ttaacccccc atgtgcttgt gagacccttg gaccccaaag 289380 ggctcctgac tggctgggcc cactccttct gtatatggag ccatagggct tttctctggc 289440 ttcccagttg aagcattgtc atatgctttg atgctcagca tttctggcaa ttttaccttg 289500 taaaactccc gtttcgacat tctgaactta agtagaaaat gggaatataa gcctcttgtt 289560 ttttgctctt aatccattcc agaactataa gtccctgggt tcttggcaac aacaggtgtt 289620 cctctagatt ttaaatcaag tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtggaat 289680 atctcactaa aacgacagtg ttgtcatcaa ttttggcttc atggagggtc ttgagctggg 289740 tggagatggg aggaagctat ccttgtccat gcggtttgga gacttgctct aaaaaagaga 289800 ccgtctactt ccctcgtagt ttttgttttg aagacatttg tagtgtttac caggagcata 289860 cagttatctg gaaaatgcag actgatgaca atagtatttg aaatgctcgt agatctgctt 289920 ctaggttgat ggaaagaatg tatgttccaa ggtacaagtg cttgttgact tttcggatgc 289980 agccagtctg tgctctttgt caggtaactc ggaatcactc cacagtagct gtccttcctg 290040 tccatttgac aagcacttaa aagggcagtc ttaagtactt tacttcatag tttattaatt 290100 ttttcccttc tttagtttgc aatctactct cagaaactga aaaataattt cttttacctt 290160 tttccccttt ctcatttaag ctgaaattga tttctttctg agcgtgtaag gaaaaaaata 290220 aaaagaagct gtggttaata caattgcctt tgctgaacaa aaataaaaga ctagtttacc 290280 ttcaagctgt gctgtatcag agtaaggatc tgttctgtca ctcccaggag attttgataa 290340 gagagagtac aaaatttcat aatatctaca tagcataatt gtagcaaata taagaagtat 290400 tataattgtt tatttgggga tgagggtggg gatgggtttt tttgtgtgtg tttggaaaat 290460 tgggaagcta gaagatactc ttaaatccat cagcttcttc agaactcttc tcaaatgctt 290520 attgtcatga caaccatctc ttcataaacc aaggctctga gtgtaataca gatggggctg 290580 gtaacaaggt aggattgcca tctgctttgt tttctctaag ggacattatt tttttgtgat 290640 ccccaagtct catcctcaaa tctgaaagtc ttgacttatt tttctttctg gagtcagata 290700 gagctgtgag attaattctt ttctcctgac aaactacttc ctcacctgtc atcaaacaac 290760 ttacttgtta aatggaggga aaaaagggta attatgtgtg tgtgtgtgtg tgtgtgtgtg 290820 tgtgtgaaaa caaatataca tattttaatg atttatttat ctgtctactt tgcaaagtct 290880 cctatgaggt acctagtaat tcaataatac agtcaagtgt gagatccaga aacaagtagg 290940 agtgaggcaa tcattttccc atgaaacaag taaaattatt actgcttttg aacattttaa 291000 cacctgtgct tcctgatggt ggggctgcat gaagtttgta agtagtgtca tcattctctt 291060 attaggtaac aaataggagc ataattattt aggagaggaa aaccttttct tgttaccaaa 291120 tttggtgaga aatttgccaa agaaatgaat gcttacagga gggatacagc ttaatatctt 291180 catactcccc tttgtcaaag atacaagtga cattttctca tatcaacttc ctacaaaaag 291240 tgaggccata catttttaaa aagaatatac ccagtatttt aaaagtttgt atatatcgtg 291300 atcagaatta agatatatcc agcttttgaa aaaatataca tatttagcca ttaaaaggta 291360 tgtggtaaac taaactgatg aataaaggtt atgggaaata tttcataaaa tttatattta 291420 aagtaaagaa caatttctct ctttgtatta tagttatttt acataagcta caatctataa 291480 ttctaaacct taatttcttg aagggcttta taagcctcat ttttctttct aaatagagaa 291540 gttcatacac tgcttttatg tcctatatgt tgatgtgtaa aaataatcaa atactagtgg 291600 gtgagtagaa tgtaactaca atatggtaca cacacagaca cacaggatga ctaaactgtg 291660 cacatgagct gatgtccaga gcagggaaaa gctgctaaag aatgtttgaa gtagagtcag 291720 aatgcagttt tgtggttaag accaataatt tttcaaagga gcattataag gagtgtggtt 291780 acttgggttg gagttgaaaa ccaagcaaca gttgggcaga cttgaaacca gttttgtctt 291840 taggtttctt ttcttaatga ttggtctaca atgagttagc cactcatcgt atttaaggtc 291900 ttggtaaagg agagactttc tttgccatgt agtttatacc tcatgtatgc attacagtag 291960 agagctccag gaaatactgc aggccttcta ctggttttta tcctctattt agataaaaat 292020 gaggaagaag tagaattatc ataaacaatc ctgttggctt ttagttgaga tatactacag 292080 aaacatcacc tttgaatctg tatatgtaaa aaaaaaaaat ctcagagtaa gatataagtt 292140 ctgttgcatt gttctgaagg aatgggtaat gtcagaaatg tcttcattac attacataaa 292200 gtaatacaca gtgctgttat cagattgcat agtcaaagtt ggcaagtttg catatttaca 292260 tagatatcat gaccttcatc attcatactt ctttcaagaa atggtcatct taatatgggg 292320 tatttatttg aggcatacac catttatttt aagaagcagt acctttgttt attgtaaaac 292380 ttctggacta aattcttcaa ttttttctca aatgaattca gttttttgtt ttttttctta 292440 ccactggttt ttactgcata gcgtttgcct gaagaacacc actttgtttc ccaaggcaag 292500 tagtcactac aaggcgagtt ttgttctgtc tatcccaagg caaatagaca gcagcaaaca 292560 tagtgtggag ggctgctggg ttcagtagaa aaccatcaac tatttctaat tgggggtgta 292620 tgaagacagc tgcattctgg acatgctaaa catcttgaaa tgcttggagt gtaataaaac 292680 cccaaacgtg ctttcttttc tcatttcttt gcacatgtat tttaggcaaa atataatcca 292740 catgctgttg ttccctctcc ttttaaatca tgaaaaatgt tgtttttata gggctatttg 292800 aggtccagga tgccttttta tcctttttat taggttattt ttatatataa atgaaaagaa 292860 aaacataaac agaaaataca acatgacatc atgaatgagg gcaagcacaa actgcccaat 292920 ttaagtttga agttataaac ctaaaatatt ttaaaacaaa acatttctct tggtgttttg 292980 caaaagtaat gctttcttct attgggcaga aattgcagcc tgttgggatg aaggagagaa 293040 tagaactaat atttattgag tagctaccat ggctttctgg gacatctgct aaccccttaa 293100 tttttacagt aaccctaagt ggtaggccag tccatctgca ttttacagac aggaaatgct 293160 ttcagagata ttaattagat ggctgtagac cacagaagaa ttgaaagtca ggtcttcttg 293220 acttttcagc tcatgacttc attacttctg ccctcctcat tctgttggga gatgggtggg 293280 agtgtgccct ccagataatc agaaagtccc atgttgggat gtgatttgga aatagctagt 293340 cctcaggcct gtggacgaag gctattgtag cctcaagaaa gaaagagtca gcttgatatt 293400 ggcaaggtgg ttatttagtg tggcagctgc ataagagcat tggataggtg gtatgatatg 293460 ggatgggggt cagggtgaga gctgctcaca cctccttatt atggcagggc aaaaccagaa 293520 tagtcacagt gatggtgatg tagggtaggt tcaagagaaa gctcatgttc ttctagcatt 293580 gagactcaca atatttcaaa acaagtgatt atttattcca ttactattta ttttggtgat 293640 ggatgttgca tttattttat tttctaacag tagtacatat ttggtaagag ttgtttgtga 293700 cattctttat ttaaatggat taaacccatt ttcttaattt ttttaagtgt ttgtcctgtt 293760 atcgaagata tcttaaagtg ttacagaatg ggaatcatag ctttaatgag tctgcatata 293820 agagagtcca aacatttttt ttttggagag aaggaaggtc atttcaactg tactatagga 293880 acgatagggc ccatgatcca tggtatggca ataagttact attttttgga gaataaatcg 293940 caaaatatgg gacgtgaaga ctgcttggta tttacacagg agtctagttc ttctgatact 294000 atatattcta taagctttct cccagaaatc caaagtttta tttagcttgt agccatcatt 294060 gtgccacaat cttccttcca tgatttattt ttttcccata ctgtactctt gcactgagtc 294120 tttggcattg aaagggaaag agatgaatta ttcaactctt cttctattga gtgaaaagcc 294180 aatacagaaa aaaaaatgca acaggcaatt tcatgactga cattttggag aacattgggg 294240 tcatcatatg actgagaaaa tgattatctc ttttgaaggt caggaaacca atattttttt 294300 ttccagtgaa tctactgagg gaaccaacca cctagctttt tgtaaatagc actcctcagg 294360 gaaatgttgc ttttttcttt tgcagtgttt ctgctttgaa tcttcataga ctgtatccca 294420 tggaagcagg aatataatta ctgtagtgct tacttttttt catgtctcta ctgaagagcc 294480 accctgattt atcttttact ccaaggtagt gtggaacttt acaaggattt agattatatt 294540 agtcattttg cttggagatc tctgcacact tttcaacatc atttctaaga gccttgccac 294600 actcagtaaa agagggtgag gcttcaagaa tctctgtgta ccaacgcaaa ttaggcaatt 294660 tgtaagaagt ccctagtaga gcagagtgga gagagggctc aggatctcgt gaggcctggg 294720 gcagggaggt ggacatgcta tgagctcctt tcacagtcaa cacaaagtta acacatcttg 294780 gaggaaaaac cgttactgta taatggaagg cagaaggcag ggatgtctgt gcttggtgat 294840 gaagctataa gtagtgagct gatttatgat ggaggggtga attgtgccat gaaagagact 294900 cccctcaatt ttattagcca gattactgcc catatgcggg gtgaggagtg agcattttaa 294960 ggcatttctc tctgttttca atatatcatc tctggattca ctattactgg gacttgtgaa 295020 tatagactag ggattaaaac ctgagtttgc ttttaaaaaa ctttatttta ttaaatgaga 295080 tttctgagca actgatttca cttagtctta tcaaactatt cttactactt tttcgatatg 295140 cattctgtcc ctcctgtgtg aaggccacag gcccatggcc cccatgtcat tgagatggag 295200 gtcctcaagt gatggcggga tgaatcacct ctcacttgcc acctgcgaga atgtctatca 295260 ctgatacctc tccttatgtc ccgtagcagc tgctaagctc ccacgttatt attggtgaca 295320 ctttctagtg ttcaggagag aacaggattt actttttgaa tgcctctaaa ttattatagc 295380 aggttcattt ggaattgcat atcagaacat tcttcctgtt tatcaggaaa ataaaccaag 295440 gtcttgaaac ttgatgtcta tccatagttg gcccaatata attttgcatg tggtttatta 295500 cattattttt ctccattggc tatgaactga aggcatctca tggatattta ttccacgctg 295560 aaaaggtagt tagatgctgt gtggtaaagt cgagaccagt atattggaag aaaagagaca 295620 ctccatctaa taatctttca tagtcttcac attcattgag aaggttactt gataaccttt 295680 cctgcacact ctctcccaac cctgacccag gaacttgcag agcacactgt gcaacagatc 295740 taataaccct tgtctgcagg caatatgcac agctgggaaa gataattaaa tagactcttt 295800 ttgagaggtc tacaacattt caacggaagg atcgagcaat ccggctggcc tccgactgaa 295860 aactattacc aacagacata cttcagacag attccatgat caccatcctt atgtggcaca 295920 agtgcttatg gggagcttct ttggcttcca aaaggccact aaaactgtca gacctaaata 295980 atactggaac tgtaaagtgg gaattaaaaa ttataattcc atttaacatg taacgttctc 296040 atcagaaagg ggcctttggt tttccatatt gatcggttac atggtcagct gcaattgtaa 296100 ctcatgagac acacccagat atcatcctgc gtgattcttt ttgaggttta tttagggtgt 296160 tagataatcc gaggtaggtt tcatcatggg tggcaatatt acatatagca aatgtcatga 296220 gaagagagac aaagcctccc ttttgaatgt taacatttat gcaataagtt taatgtaccg 296280 tgtaagttta cattactatt atgagactta acctaaaaaa ttggggtgaa atcttaaaga 296340 attatgaaat taagaaatga aaccagaggg ctttcgtttt aagtactgat cacttaaacc 296400 aaaaccagtt tggcttatcc tatgagatcg tgggtattga gaaagaggaa catttgctgc 296460 tgcatccgga gatgtttcct tgagagcaag actagttcct tttgacccag tacatcctac 296520 aggtaaatca ctgcatgctg tagagatacc tgttccctcc cttcccccac cccctgggga 296580 tctgaaacca aatcattgct ttttcatctt ttacttatcc ttataaacaa agccacccac 296640 tttctcattt ttcctgatgc caagtccttc tttacatgag tggaatccac tcttttcaat 296700 ggaaagacac ctgctctgag acaggctaca ctgtcatgag ccttggcatg gctgagtgat 296760 gtagtggaag gtgcaataaa tttaaacttt aaaaatgcaa aatttgatgg aatcatgcat 296820 cttgtgccta cagtgagtat atggtctagc aggatttaca gatacatgca tgattaattt 296880 gaatacagta tagcaaaatg atctgttaaa aaacacatga aaagatgtgc aaccttatta 296940 gtcattagga aaatgcacat aaaaccaccg ttcctgtgtg atacctctgt acgtctatta 297000 gaatgtataa aatttaaaaa gactgaacat agcaagcact ggtgaggttg tagaccaact 297060 ggtgctttca tgttttgctg gtgagaatgt aaacattaca actactttga aaacagtttg 297120 acagtttctt aaaaagctaa aacatccacc tggcatgcta tatacagata tcctactctt 297180 acgtatttaa ccaagagaaa taaaagcata tatccattca aaaacttgta aataaattgc 297240 tcctagcagc tttatttgta atagccaaaa actagaaaca acccaaatgt ccaatgaaag 297300 gatacatcgt atttatttat aggacatatc catgcaatgg aataccactt aggaatagaa 297360 agaatcaact gttcatcata catacaacca catggctaag tcttaaaaat aattatgctt 297420 agttaagaag tcagacaaaa aggtaagaga ctgttaggag ctgaattagc gggttaacag 297480 tggcaatgaa aaaggagaaa attatagcta cctcaagata gaattgatga gctttgatta 297540 tgaaatgatg gtaagagaga gggccataga ctctgaggtc tgtctctagc tttggtttcc 297600 ctatgtggat cattatctat ttggatataa gaattatctg aaagatgata cttaagcatg 297660 taagaaatga taagctacct gtttaatgat gagcttttgt tacctccaag aaccccaaga 297720 agaaacatcc tgtaagcaga ccattcatac ttgattgtta aaggaaaaca aaattccatt 297780 ttgtcttttt catcaacaca agtatagctg gctaataaaa gtgtaatatt catgagagaa 297840 aaagaaaaga acacgcacac acatacactc aacaggattc ctagagtcat tcccatggat 297900 aagagggaag gaaaggttga gggcaaagag agaagggaag gaaacagact atgatgggat 297960 atcttagggc aaaagaatag ggggctgatt tggaaggcag caaacttcat ggatacttga 298020 tttatttaat gtccctgtca ctctggcgta tcttaatgtg tgtggtgtgt gatttattta 298080 gtcacttgat ccaaattctc taattaagtg gagctcagaa gatatagtgt ccattgtggt 298140 caagggcaca ggttttggct tcaacagaca aataagctct ctgagcatct gtcttctcat 298200 ctgtacaatg ggaatatcag ttcctacctc ttcaggttgt tgtattcata aataaattgt 298260 gtacaagaaa cattaggatt gcttcttacc cgtagtaagg gctcaacaaa ccttctcctc 298320 cttctcctcc tccttctcct tcttcttctt cctcctcctc ctcttcttct tccttttgct 298380 tttctccttc cttcttcctt cctttcttcc tacctccttc tcattattgt tattaggtaa 298440 ccacaatatt atcagtaatg attggagaaa gctttaatct cctagttcac cattagaaaa 298500 caagaacaca ttttggtggt tattacccga agtaatcata atgtcacctt tttttccatc 298560 tgactcatta tcccaagtga tttatttata tatggagttt tctgagtctt tcttttacat 298620 attacaaaaa aagagtgtga tttagggacg aagcaaagaa ataaaaattt agtgactttc 298680 attctgcctg tgccccaatt cctattgggc ataaggcaag taatttaaat ttcttagcac 298740 cttagcatct tctactcaaa cagaaatgag gaacagtcac aggttactat tatagctgtc 298800 taagtagaag gcacacaagt tttcacactg agtataacac tttatagaaa gctaagtgtg 298860 ttgctcaagt tggtacattt ctgtagatgt gacactatgg cactaagaaa cttaatgcca 298920 cattgaaatt cattgagata gctagacttt aaaaataatt acttgacttc actataaagt 298980 atgttcgtat tgcatttact ccatctagta gaaaatagac cttgtcagtt caaatccctg 299040 ttgcattaat ttcaccagta atgagtcttt ttcatttgag tcagcagggt ttttcttgct 299100 tgttttcagg ctttgtggat ttgaccctcc atgatcaggt ccaccttcta gaatgtgcct 299160 ggctagagat cctgatgatt ggtctcgtct ggcgctccat ggagcaccca gggaagctac 299220 tgtttgctcc taacttgctc ttggacaggt aagtgacctg gctgtagctt aggagtagca 299280 tgttctttac gatcatagtt cattcatgaa actattttat tcatctctcg gtgaagcttc 299340 agagaacttt attaggtatg tttacttaac aaaagagtgc attgggggtg atgaagccta 299400 gtcaaattca cagaaagcta aggataactt tctgctagac attacctcag aagaattcta 299460 ttatttctaa tacacacaca cacacacaca cacacacaca ctcacactct ctctctctct 299520 ctctctgtca ttatgaatgg taattttcta actccatctt caacttgtat catataaaaa 299580 ttataataac ctctctttaa ttaaaatctg ttgttgcttc ttgtacatcc ataccacaat 299640 agcctattca ttttcttctc caattttccc atccgtaaaa tgaagaaatt tgaccagagt 299700 tctgaaggtc acattcaggt cgacaaattc attttcatgt tcaaatatgt taccttcttt 299760 aacataccat tctggggttg ccttggaatg tgggtcccat tgtttttttt ttttcagtca 299820 ttgcttagag tcatagaatt tagatattac tcaatagcag ctgccactga tagagtctcc 299880 accctgcacc agctgtgatg ctaaacactt tacatatatt atctcattta atcatcaccg 299940 gactcctagg aggcaggaat gtcatcatcc atgttttacc agaaaggaaa ctaaatctca 300000 gagacatcct gctacttgca aaaagaggaa agctcactaa atggtggagc cagagttcaa 300060 attcaagatc tttctggctc cggtatgctc tgttacctcc tgtgctgggc acatggtctt 300120 cccactctca tgttcagtga tgcctccttt ggtctgctgc catagcattc tgttttccag 300180 gtaaatcttg tctttgtggg ctacataaca ttttggatga gaaagaacca ttttgttgtt 300240 tcttgcaatc ctattttgcc tccgtgccaa gcagtctaag gctgccaggc tgcccacagt 300300 gcatctctgc atggtacttt acttcagagc atttcactat ctttctacac ctgccaagtg 300360 cctggagcag agttgcagca aaatttattt aagtactgga gaattgtaca aggtgttggt 300420 tattgttttg tcattttgtg ttaacacagc ttttgaaaaa cagtggtgat acagtttaag 300480 aagcatattt tgctgtctgt ggaatatatt ttgatatcac agtttcacaa aattatcaag 300540 aatggccact agtcttgttc cttagaactg tactcacaat gtattctgtc agccttatag 300600 aggatgtctt taccgtgttc tttcctttcc attccttgtt tcctttccat tttttcctat 300660 ctcatttctc ctctcttttc ctttgctttc ctctttcttt ctttctcctg tcctcttaat 300720 ttttttgtct tatagcagtg tggttttgta accaagtgat atcaagtttg caaatgaaaa 300780 tcttagacca cacgtaacat ttccctgcct actgcctgga gtgtctacca tgtttaggtt 300840 tttggacatt cataactcat ttgctccttg atttccatcc tcatctgtat ctatcttctt 300900 ttttaaaatt taattcaatt tttataatgt tgacacaatt atgcagattc atagggtaca 300960 cagtgatgtt ttgatacata taatgtgtgg tgatcttatc tatcttcttg agtacacact 301020 tgcttgagga cagtcatcaa ataattgcat tttgaatatg tgaaggtttt tgacattact 301080 gcacccaaaa aactcatatt gccagtgagg tgatatggcc taggatttta tcagctacag 301140 ccttctcttt cctttctgta cactccagtg gtggctaatt ttctttcctc tctcacagaa 301200 gtatgaatga ctaaaagttc tcatctctat tcattcctac tttctaaaac ttcagatcgg 301260 aaatttgaat tacctctaga ccaggatttg tcagtctctt tactattgac attttgggtc 301320 agatcattct ttcattcttt cttggttgag gggttgatat tgtttggtgt gtcctcatcc 301380 aaatctcaaa ttatagctcc catagttccc atgtgtcatg ggagggaccc ggtgggaggt 301440 aactgaaaca taagcaaagg tctttccctt gctcctctca tgacagtgaa tttctcatga 301500 tatctaatgg ttttataaag gggagttccc ctgcacacgc tctctctctt ccccgttgcc 301560 atgaaagatg tgactttgct ccttcttccc catgattgtg aggcttcccc agtcacaagg 301620 aactgtgagt ccattaaacc tttttctttg taaattaccc agtctcaggt aggtctttat 301680 tagcagcttg agaacagact aatacaaggg gctgtcttgt gcattttagg atgtttaaca 301740 gcatccctgg actccaccag ctagctgcca gtagcaacct ccacttcctc cagttacgat 301800 aactaacaat gtctccggac atttctacct atcttctgtt gtgtcagggg gtgggggagg 301860 taaaattgcc tctggttgag aatcaccact ctatgctttc ccaactcaat gttctataag 301920 ctcctcagac acactgtact ctaaactgca cactcacttt atcttctgca acaagtctat 301980 tccttttctt ttctgtcttg gtgacatcaa cactcaccta gacactaaag ctagaagctt 302040 taagttaccc atggattcta ccttctccct caccaaatta tccagttaac tatcaagtca 302100 tctatgaact gcttctgaat ccagacctcc cctctatccc cattcctctg catggcacag 302160 gtcctggttg tctctgctgc agattccttg cttctgcacc actgactcac tttcttggtc 302220 ctgctactct ttctttcagt ccatctccca tactgctgct ggagaaggct ttctaaggca 302280 cagctgtgat catgatgctt cctgactcac ctttcagtgg ctctctcaat tcttaacatg 302340 gagaaacccc atctctacta aaaatacaaa gttagccggg catggtggct catgcctgta 302400 atcccagcta cccgagaggc tgaggcagga gaatcgcttg aacatgggag gcagacgttg 302460 cagtgagcca aaattgtgcc attgcactcc agcctggatg aaattccgtc tcaaaaaaag 302520 aaaagaaaat actgtgtaga cttcttatct taataatcat gaatcactat tacaagtgtc 302580 tcaaacgcaa atttctgaag agtcacaggt gacccagtga gcccttgtcc aggctaaaaa 302640 cacctggtgg ctgaattctg aacttcacac attcgaattt ctcttccatt gcttctgaga 302700 gaccctccac cattacggtt ccttatcaga gtcatatcta cctataaggc tcatttcagg 302760 tgccgtcttt ttataaaatc ttccttcaaa ctttctcctc ttcagccttt atatatacaa 302820 aaggcttttc tttcttttcc ttttctaagt ttccattgta gttggtttgc ttttctcttt 302880 attattctca ttccaccata ttagttatga ttggatgtct tcttaccttc cctactagct 302940 cataaacttc ttgtggtcaa aaaccagatc ttgttcgtct tgtgtgatct ccagtttacg 303000 aagtcttcca tgatacccaa caaatatttg ttaattgcac tggccaaggt cacccaggtg 303060 gcttgtggcc aaatcagaag aatctacatc ttctgatagt catggcagct gttattccca 303120 tccaactcac ttcctgtgca ttgctactca tcaattcccc acttattctt ttaaaaacat 303180 tgcataaata catatctatg tgttttggaa agattttctt aatctataag cgcatttggc 303240 gtgtgcttat atgtctgctt atatgccaaa tttgaaattc caaatttcgc catttggaat 303300 ttcaaatggg gaaaagcaaa gactcttatc tttcccataa tcaaacccct tatgaagtaa 303360 aatccttaag gtctctctac aggttaaaaa taattaggtg atatgatttg gctgtgttcc 303420 cacccaaatt tcacctttaa ttgtaataat ccccaggtgt caagggtggg gccaggtgga 303480 gataattgaa tcatgtgggt tgttttcccc atactgttag tgtggtagtg aataagtttc 303540 atgagatctg atgattttat aaatgggagt ccccctgcac aagctctctt gcctgctgcc 303600 atgtaagatg tgactttgct cctccttgcc ttccgccatg attatgaggc ctcctcagcc 303660 atgtggaact ctgagtcaat taaacctctt tcttttatat attacccagt ctcaagtatg 303720 tctttattag cagcatgaga acaaactaat acattaggta tatgttaatg atgaggaatg 303780 tgtataaata catatacatt tatatttaaa tattaatatt tacaaataac atgatattaa 303840 aaatatggtc tataattttt taaattatct acctttctaa tcattaacat gcactaaata 303900 ttattaaatt tcaatattat ttaattacca tcttggtgtt tgaggataac tgcttttgat 303960 ggcattgata gatgcattaa cagtgaaaca ttgtgaccaa cagcccatct gagattttat 304020 acttgtagaa gatggcttct gagtgacagc tgagaagact gtttatgtct ttgccctaca 304080 ggttcctaac ccctttaata aaatagagct ctctgatgca gatgacacat gggccttctt 304140 tttgctcttg tcccatcaca ttgtacatag taaacatttt tagcaacaaa tagtagatac 304200 ttataacttt aaaagctaag tggttgacag ctgagaggca gatgatggta atttcatcat 304260 ttttctcata tctcaggcat tgtgacacta cctctgcaag gtcaactgtc tccataggct 304320 gttttcattt gcgtagaaat aggggggaaa gatagcttga agtcatcagg agccctgcaa 304380 cccatggatt accaatgttg ctaactggag cctggatttc atcttcaatt gattgtaatg 304440 atgtcttgtt ctctcaaatc tttgcaaatc taggcattta taagactatc ctgtaggtcc 304500 cttacaagac catgaggatg ctagaactta ccctagtctt ttcttgtaat tgcttaaatg 304560 ttagtattgg caaatggggt ttggtgatta taagagtaaa aaaacctgct gccatcccac 304620 atttgtgagc agaggataca tttcctatct tgtgtccatt taaaaagaat gattgcttga 304680 ttggcttcct gatgacaacc catgatatac tgattctgtt agtttataac tttcctagta 304740 gtcatatgct tataggccaa ttttatcctt gccatgctta gcctagtcac aatttccagt 304800 tcttctctgt atcctgcagc agtgagttcc aaacacttaa tgctgtcatc tcttcctgtg 304860 aaaaccaaga aataaaggtt attataaggt ataaataaag aacccagtga tttctcttgg 304920 ggtgtgtgtg tccatgtgtg tgtatatttt acaagaggaa agttaaagat actaagaatg 304980 cctgtgaaag taatcaggaa atggagaaaa cttgttttcc attctagcac ctaatccttt 305040 ggtgtgtttt ggcactagaa aacacaaaat atgtcctctg tgtctactag gaatgcctct 305100 cttcatttag tcctgcttga gtgctcatga tggaaaaata tagactgaaa acaggagcaa 305160 aagtgttcat cctactcatt ccttgtgggg tctctttgct ttcaaagaga tgttagagat 305220 gttagtaaat ggtgttagaa gaaacaatgt aaattgcctg tttagtaaga tgatccagtt 305280 tctaaggaac tgttttactg gcgccttcca tgctaacaaa ttctgagaaa tatttgcgga 305340 tttctcagtg aagccaaagc actctctttt gactcctatt tactctcaga gaaaaaaact 305400 attcatccat ttgaaaagca gggaccaatt caacaagcag aatattccct ctactaagcc 305460 tttggccaga gagttgttgc tctagttctt tccatcactc ctgcatcagg aggctctgcc 305520 tgcaggaaat agtattggac aacagaaagt tcttttactt gtaggcataa aataggtata 305580 aattctcctc cttaagagaa aaacaggttg ctgcaccaga aagaacattt gcctcttcta 305640 ctaaatagca gactgttttc caatgataaa ctcattttaa atagaaaaaa aaaagtcatt 305700 ctctacaaac aagaacattt tcattttagg ttgtttattg taaatatttc agaaaaaaaa 305760 tatgcaaaaa aaaaaatgcc caaaaatcaa tgcttccagt aacatattta ttagctatct 305820 ttttccccat gtaaaacttc aggtaaattc tttgcagatt ttttacttgg aagaatgata 305880 aaaaaaaaaa aaaaagttct gaaatgagtt gaattcatcc acgtgtgttt ttgattcaca 305940 tgaagagtag gacctccctt tatattccct cttcaaattc tcccctctga aaaatgggtg 306000 gtacactcaa aggaggaccg cacacattgt agtagctggg gtgttggggg tggaaggagc 306060 aggttttggg ggtgggagga gcggtgagtg atcctttcag caaagtcagt cctgggcagg 306120 agacggcttc aggaatactg tcagctttac tggattccac catcgctttc caggactgtt 306180 taggccctgg gcccttgaag ggtttgcgtg cctcttgtct ccattcatac ctcaagaact 306240 ttgttcatgt taattttttt tcactctatc atatggaatt gagtaaaaaa agaaaaaaaa 306300 aaggaagcca acacttactt aactgcttta atgtatagga ctctgttctg ggttgtcttc 306360 taaagtacat ttcattcaat gtgtgagaat acagatagga aagagttttg ctagtttcta 306420 ttttgactgt ggatccattg attctttctg gttctcagcc cttaattgct cagctgcaga 306480 taccacttga ctgactctta aaagtctttg gtttattgcc caattctggg aatatgaaac 306540 tgtaagctgt ttaggagaaa aactgagacc aaaagaaagg agaagtgagc caaactgcca 306600 ttatgattgc cacttcttat tgaagataaa tcaaaatatc catttgacta gaaatcaatt 306660 gaattatgca ctttaaatgg gccaattcaa tgatacctga actatatctc aaaaaaggtg 306720 ttaaacacag gcacacacgt acacacacat attggaattc caggaaaagt cactttgatc 306780 aacaagatta tcagtcgtca aagtgcttgg aagggttcta ttggaataaa gctaaaaaaa 306840 atcaaagtaa aatttctcct taaaaacaaa agcaattaag cagcactgta ttataaaata 306900 tgctaagctg caagtcaaaa ttcttaagag acttaagcct gtaagcagta aggatccact 306960 caatgtaaag ttactccaga gggaaaggcg tgagcccaac caaagtatta atgctgtgta 307020 ggaggttaat ttgactcttc ttaacatttt tacacaccac attatgtttt attcaccatt 307080 tattattaac tgaatttatt aaagtataat caaaataata tttttgagag tttaaaaata 307140 ttctcataat atttaagtta catatactat gcagggaccg tcaagtaatt ccactctgac 307200 atctgtattt attaccgcca cctgtccatg atggtattag aaagatcctc atttgtttta 307260 atggatgcct ctaaaatcca gttttaagag ggggttggcc actttcaagt ttgtgttagt 307320 taggattcag tttaacccag ctcaacaggt atttactaag taccagcata tccatagggc 307380 gctgtatgat actggaggac acacagaaaa gagatgtgta agaggcactc ctgccctcaa 307440 ggagtttact attgagtggt agtgtaatat gaataaacaa atgaatctgc tcaaaagcag 307500 ggcattctaa gcaggccctc accagcctct catcattcgc atctagtgta tcttcctcca 307560 tcactttcta aacgctatgg attctgagtg aaaaccaatc gctggtttat gcatgtatgc 307620 atatatgaat tcattcttga cattgccatg cagagtattt agtataacta gacttattat 307680 ccatttatcc tgcctagaag catactgtaa tatatataac tctaaaagca agatcattcc 307740 ttatgttggt tcttttgagc tggcaggggg aaagcagagt atgttggcag gggtctatca 307800 aggtagatga gcccagtttg tacatctttg aaatattacc aatgccaatg tgttagtact 307860 gcttggatct cttctatgac aacagttctt attttttcct tttttttgtt tgtttgtttt 307920 ttgagacagg atcttgctct gtcacctaga caggagcgca gtggtgtgat ctcggctcac 307980 ttcaatttcc gcctcctggg ttcaagcaat tcttgtgcct cagcctacag agtagttggg 308040 attacacgca tgcgccatca tgcctggcta atttttgcat ttttagtaga gatggggttt 308100 tgccacgttg gccaggctgg tctggaactc ctggcctcaa gtgatctacc cgccttggcc 308160 tcccaaattg ctgggattac aggtgtgagc caccacacct ggcccatcag ttcttaattt 308220 gatgaatgga tagaggtttg gcttcaaata aatggagtta gtctgtcaat atctgtttct 308280 tttaaaattt gcaattgttt ttatttttag tgtcatgcta tgtgccctta atgatctaga 308340 attaagttct aatctctacc ctggtataat tgatttctcc ctgtggactc ctaatataag 308400 aagaaagatg aagtttttct tttaatgctt ttagagatct tcattaagtc atttaatatt 308460 cttatttgct atttcccagt gtgatggtta agactgagtg tcaacttgat tggattgaag 308520 gatacaaagt attaatcctg ggtgtgtctg tgagggtgtt accaaaggag attaatattt 308580 gagtcagtgg gctgtggaag gcacacccac ccttaatctg gtgggcacga tctagtcagc 308640 tgccagcgaa tataaggcag gcagaaaaac gtgaaagggg aaactggcct agcctcccag 308700 cctacatctt tctaccatgc tgaatgcttc ctgcccttga gcattggact ccaaaatatt 308760 cagttttggg actcggactg gctctccttg ctgctcagct tgcagacagt ctattgtggg 308820 accttccgat catgtaagtt aatgcttaat aaactcccct ttatatatat cctattagtt 308880 ctgtccctct agagaaccct gactaataca cccagtgtgt tcttttatca aatagaaagg 308940 agatatagaa aacacactgt ccatgtcttt gattgttaca ccacagcaga gaatcaattt 309000 cttaacctgc ttacttattt accattctcc aatggtgcca attctgagat ccatcatgac 309060 tttatcatta gaaaagggga tgtaacaaac atgatgagat gttacgggaa tactgcttac 309120 tgcatgatat ggtttggctg tgtcctcacc caaatctcat cctgaatttt agcctcccat 309180 acttcccacg tgttgtggga gggacccggt gggaggtaat tgactcatgg gggtggtttc 309240 tcccatactc ttctcctggt agtgaataag tctcacaaga tctgatggtt ttataagggg 309300 ttttcccttt cacttggctc tcattctctc ttgcctgctg ccatgcaaga catccctttg 309360 ctcctccttc atcttctgcc atgattgtga ggcctcccca gccatgtgga actgtaagtc 309420 ctttaaacct cttttcttta taaattgccc agtctcatgt atgtctttat cagcagcatg 309480 aaaacggact aatacactgc atgctcagta tactcaggca ctctggaaac taggtttcta 309540 cttcggaccc ctgagagaaa agggttatgt atctccaagt gtggtcatga caagcatcac 309600 tactgtgtgc agttgggcct gtggattgag ccaccttagc ctctgaggaa agcagaacct 309660 gagagcatgc ttaattcaga gtgtgtgtga cttggagtgt ggaaaggaag atttccagat 309720 ttgcggtatt ggcgactgaa aggatggcaa tgctattgat ggagattagg aagacaggag 309780 agaggtagat gttgagcaac tccgaggagt ttttcctcat acatgttggg tttaaagtgc 309840 agggaagata tcctgaaggt tattccaggc agaaatttgg agctcagaag agacatcaga 309900 gctgaagata aaaaatttga gagccatctc cgtagctaaa agtgtggaac gaatgtgatg 309960 actagacaag ataatagaga aaaggtatcc aaaggcctga ggtcaagacc tcttaaaagg 310020 ctgacttttc agggttttag gtagaaaaag agtcccagcc tggggttaag gcagtttttt 310080 gagaagtaga ggtacaaagt tccttgttcc aaaggaaggg tgtctttcaa aagaaaaagg 310140 atgggccggg tgcagtggct tacgcatgta atctcagcac tttgggaggc cgaggctggc 310200 agatcacctg aggttgggag ttcgagacca acctgaccaa catggagaaa ccctgtctct 310260 actaaaaata aaaattaaaa attagccggg cttggtggtg catgcctgta atcccagcta 310320 ctcaggaggc tgaggcagga gaatcacttg aacctgggag gcagaggttg cagtgagcca 310380 agttctcacc attgcactcc agcctgggca acaagagtga aactctgtct caaaaaaaaa 310440 aaaaagagag aaaaagaaaa aggatggtga attgggccaa ataccagaga gatggacagg 310500 agtaagaaga aaaagactaa agatttgttc atcaggagct cattgtttct aaagggagca 310560 tttttagtaa agaggaagga ggaataaaat gcagtataat atgttaaatc taagtataat 310620 ttataaaaga gaaaatgggg gtggaatatt acaaaaaagg aactataaac cagctctttg 310680 aggtatttgt cagtgaggaa aacagtgggg ctctagttct tgatagcaac agcatcaaag 310740 ggaacttttt aaactaaaat attatgaatt tttcaaactg aaataatgag agaataatac 310800 aaagaaatct catctgccca taatccaaat tcagtagtta ttaaaatttt gccccattgc 310860 ttaatccatt aatctcattt cattttgtcc tttttctttg tttatttttg gctaaaacat 310920 tttaaagaca aatcctaaat atcatacatc agtaggcatt tacaaaaaaa tttcttgata 310980 atcacaatgc cattctcata ccaaataaac ttataataat tctgtgatat catctaaaaa 311040 acagttcttt tctacatcaa aaatgtctgt ttatagttga tttattcaat ttagagtcca 311100 aacaagttcc atatattaga cattaggtca ttaatgtctg tctatttgaa tttataacaa 311160 tttccactta atttattttc tccagcttct gtggagacta ggtaagttgt tttgtagctg 311220 tctggatata tctgattgct tccttgcagt gtcatttaac ttgttcctct atcctcagtg 311280 tttctgcaca tggaagttag cctcatagca ggggttggca tactttagcc tgcttaccaa 311340 atacgactcc cttacatttt tgtaaataaa atgttactgg aacactgtca catatgttgg 311400 ggtcatagaa agagtttccg tgtccccaag ttataattgc attcacttat attttcttct 311460 agtaattttt acccttacat gttaggggtc aatttggaat ttctcttcat atacagtatg 311520 caataaagaa tggcttttat atttttccaa atgtatattc agttgtctca acaccattta 311580 ttaaaaagtc agtatttctc aagtgatttg agatctaccc ttaattacac agtaaatttc 311640 tctgtagtct tgtctttttc taatatgtta attctgtacc aagatttgtt catctgttaa 311700 tggatcaata tcacatagct ttgtttatag aaggtgcaca ttgttttaat tctggccatg 311760 ctatcccacc aaatattgcc ctttgatttt tcagagtttt actgtggatt cttccttgtt 311820 tctttttcta tgtgaccttt agaattaact tgtttaattc tataagtaaa tttattgata 311880 attttattga aattatgtaa aatataaatt ggcttaggaa gtactgatat ctccatgaca 311940 ttaagtcttc atatctaaga ccaaggggtg ccttttcatt tgttaaatat tctttgtgtc 312000 tttcagaagt gttttcaagt atccttatgt gtattttgca caaattttta tatttgtgcc 312060 tattggatgc cacgtgcagg gttaaaaaat attataccta ttttatatag atatatatgt 312120 atataaaaat atatattata tatagttata atacataaat atattttaat atattatata 312180 atatatacat gtattgtatt tatatatgta tttatatgtg tatctataaa tatacatatg 312240 tatgtatcta taaatataca tatatgtgta catatacaca tatatacaca ttatatgtat 312300 gtttatacac atataaatac atatataaat atactagaaa gtccatgggg tttcctagta 312360 tacaatcata ttgtctgcaa atagagattg ttataccttt tcctttctat tccaaagtgt 312420 ctaaaagatt ttttcttagc tagtggcatt ggatgacacc tataatgtct tctaaaaata 312480 gtagcagtca taggcaccat ttccttattc ttgaatattc attcatgtta caaagtttat 312540 aggaatttct gaattattaa gtacttttaa taggaatgaa ggttattgtc attattgcat 312600 caaaattcat aagaaagttt ggtgtcaaat ttgtgctttg tgtgtagtct tcatcacgct 312660 tttttttttt tttttaacca gtgttaaaca tccattacaa aaatagtttg gaagtttttc 312720 tttttttttt tcctatgtcc tggaaggtgt aagtagaatt ggaattattt gatctttaag 312780 atgtaaaata ttggtagaat tctacctttg aaagcacctg gacatggtga cttcttaata 312840 ggtgagctct ctggaaactt tatttcttct gtagtaattg gtctccttag actttctatt 312900 ccttctggag tcagatattg tatatcaaat cttctgttaa agttatccat ttcttcttgg 312960 tattccaatt tttcacattg agttggacaa atgatttctg atgatgttta aaaaatttct 313020 ctggtttgat ggttactttg accgtataat ttattttgtg tatttatgct tcttttagaa 313080 acttaggtca gctagtggtt cctctatttt gttgattttt ttcctcaaag aactagctta 313140 agtttatttt attagttcta ctagttttct gctttctaac tcattaagtt atgcctttag 313200 ctttattaaa tccttcattc tgctatcagt taatgtttta gttcattttc tagctttttg 313260 agttgatact taatttattt tcatttcatg atataggtaa ctgatgctca gaattttctc 313320 aaagcatcag ttttcgctgg gccccataga ttctaatata tcttactttc attattatta 313380 tttcctaaaa attcagcaat ttcatgtttt attttgtctc tcattcaaga gttgtttaat 313440 agacagttta atttccaggt tggatgggca ttttgttttg ttttttgttt tactgtttat 313500 aaatactttt ggccttggga tcagagaata ctgcttgtat tacaattatt actgaatatt 313560 tttgtggtct aatataattt cagctttcaa aaatgttcca tgtatacttg aaatgaaggt 313620 ttatttaccc ttataaagat agaaggtaaa atattagcta tgcccatgtc tatttatctt 313680 cttataattt ttgcttaatg aaaactaatg atccattatc tgctgcataa gtatttatgt 313740 ttgctttctc tttattatgc cttatggctt ttgtgttaaa aagctattga tttatttaat 313800 attttggaag gattgaattt taccctatct aatatcaaga tcatgactct tgattccttt 313860 ttgttttcac ttgtttaata tatctttctt ctatctttat tttaaacaca agaagagctt 313920 tgctttcagt ttctatttta catagtctac aatcggattt tacttattag tcaatctgag 313980 aatactttta atagatgagt tacacaaata catatttatt gataccaaca cagtttaatt 314040 caagatctgt tctattattt tatatttatt atatattaaa ttgtcttctt tatttactat 314100 ttattgattt attgaattta ttttgctttc aggtattttg tatttttgtt ctggttgtta 314160 gatttatgca tacttagtca actcttcctt tataaagcat tcattttcta ctatgagcag 314220 tagtaaaatt agctagtaac ttaattcctg agcactctcc agtcctagtc actagtaata 314280 acgcagtgtt aaactttgta atattaatta tacttaagcc tctattactt ggtttgtcaa 314340 aatcaaatga tatcaattta cttccagcac atacctatga ggtaattgta agctaataat 314400 aacttccatg gctattcttt tctctttttt tttttttgag gtggagtttc gctcttgttg 314460 cccaggttgg agtgcaatgg cacgatctcg gctcactgca acttctgcct cccgggttcc 314520 agcgattctc ctgcctcagc ctcccaagta cctgggatta caggcatcag ccaccccacc 314580 tggctaattt tgtattttta gtagagacag ggtttcccca tgttggccag gctggtcacg 314640 aattcctgac ctcaagtgat ccaccccatc agtctcccac agtgctggga ttacaggtgt 314700 aagccaccgc acccagcctc tcatcttatt tttattactt atatttttct acattattag 314760 aagttataat acttatatgc acatttcttt agccccaacc ccattttttg atattagctc 314820 tattattaag atatttaatg tccaccttca gattatatgc tgatgattct ctaatcgttt 314880 ttggttgtct ggagcttttt tactgtttat tttcaggaag agctcatgat aactcttttt 314940 tctttggttt aaaaatgttt ataattattt ttctctggac tttatgctga gaaatttggc 315000 tgcatacaaa atctctggct tacatttttt ctcaagtatt tttaagtgat tgcttcatta 315060 ttttgtagta taaaatgttg ctcacaagaa gctggatgcc agtctgattt tctttccctc 315120 attagtgatt tggacttttt gtctgaatgt tgaattttta aatataaaca taaattgcaa 315180 tacttttatt aagatatgtc tctgcattga acattttagg tccgttttcc taggtacata 315240 gaatgtcttt tgaatatgta gactcaaatc agacttcttg attctcttga tttatagttt 315300 taaatatttg tttgggggcg ggtgcggtgg ctcatgcctg taatcccagc actttgggag 315360 gccgaggcgg gtagatcata aggttagcag attgagacca tcctggataa catggtgaaa 315420 ccccgtctct actaaaaata caaaaaatat agccaggtgt ggtggcaggc acctgtagtc 315480 ccagctactc gggaggctga ggcaggagaa tggcctgaat ccgggaggca gagcttgcag 315540 tgagccaaga tcacgccatt gcactccagc cttggcgaca gagtgagact ttgtctcaaa 315600 aaaaaataaa tagggggcgg ttccaagatg gcagaatagg aacagctcca gtctgcagct 315660 cccagcatga gtgatgcaga agacaaatga tttttgcatt tccaaatgag gtaccaggtt 315720 catctcactg gggactattg gacagtgggt gcaggacagt gggtgcagcg caccaagcat 315780 gagccgaagc agagcgaggc atcgcctcac ctgggaagtg caaggggtca gggaattccc 315840 tttcctagcc aaggaaaggg gtgacagacg gcacctggaa aatcgggtca ctcccaccct 315900 aatactgggc ttttccgatg gtcttagcaa acggcacacc aggagattat atcctgtgcc 315960 tggctcagag ggtcctacac ccacagagcc tcgctcattg ctagcacagc agtctgagat 316020 caaactgcaa ggtgcaagcg aggctagggg acgggcgcct gccattgctg aggcttgagt 316080 aggtaaacaa agtggctggg aagctggaac tgggtggagc ccaccgcagc tcaaggaggc 316140 ctgcctgtct ctgtagactc cacctctggg ggcagggcat agccaaacag aaggcagcag 316200 aaacctctgc agactgaaat gtccctgtct gacagctttg aagacagtag tggttctccc 316260 agcatgcagc ttgagatctg agaacgggca gactgcctcc tcaagtgggt ccctgacccc 316320 cgagtagcct aactgggcac accccagtag gggcagactg acacctcaca tggccgggta 316380 ctcctctgag acaaaacctc cagaggaacg atcaggcagc aacatttgct gttcaccaat 316440 atccgctgtt ctgcagcctc cgctgctgat acccaggcaa acagggtctg gagtggacct 316500 ccagcaaact ctgacagacc tgcagctgag ggtcctgact gttagaagga aaactaacaa 316560 acagaaagga catccacacc aaaatcccat ctgtacgtca ccatcatcaa agaccaaagg 316620 tagataaatc cacaaagatg gggaaaaaac agagtagaaa aacagaaagt tctaaaaatc 316680 agagcacctc tcctcctcca aaggaacgca gctcctcacc agcaacggaa caaagctgga 316740 tggagaatga ctttgactaa ttgagaaaag aaggcttcag acgatgaaaa ttttctgaac 316800 taaaggagga agttcgaacc cacggcaaag aagttaaaaa ccttgaaaaa agattagacg 316860 aatggctacc tagaataacc aatgcacaga agtccttaaa ggacctgatg gagctgacaa 316920 ccaaggcaca agaactatgt gacgaatgca caagcttcag tagctgattc aatcaactgg 316980 aagaaaggtt atcagtgatg gaagatcaaa tgaatgaaat gaagtgagaa gagaagttta 317040 gagaaagaag aataaaaaga aatgaacaaa gcctccaaga aatatgggac tatgtgaaaa 317100 gaccaaatct acgtctgatt ggtgtacctg aaagtgatgg ggagaatgga accaagttgg 317160 aaaacactct gcaggatatt atccaggaga acttccccaa tctagcaagg caggccaaca 317220 ttcacattca ggaaatacag agaacaccac aaagatactc cttgagaaga gcaactccaa 317280 gacacataat tgacagattc accaaagttg aaatgaagga aaaaatgtta agggcagcca 317340 gagagaaaga ttgggttacc cacaaaggga agcccatcag actaacagcg gatctcttgg 317400 cagaaactct acaagccaga agagagtggg ggccgatatt acacattctt aaagaaaaga 317460 attttcaacc cagaatctca tatccagcca aactaagctt cataagtgaa ggagaaataa 317520 aatactttac agacaagcaa atgctgagag attttgtcac caccaggcct gccctacaag 317580 agctcctgaa ggaagcacta aacacggaaa ggaacaacta gtaccagcca ctgcaaaaac 317640 atgcaaattg gaaagaccat cgaggctagg aagaaactgc aactaacaag caaaataagc 317700 agctaacatc ataatgacag gatcaaattc acacataaca atattaacct taaatgtaaa 317760 tgggctaaat gcttcaatta aaagacacag actggcaaat tggataaaga gtcaagaccc 317820 atcagcgtgc tgtattcagg aaacccatct cacgtgcaga gacacacata ggctcaaaat 317880 aaagggatgg aggaaaatct accaagcaaa tggaaaacaa aaaaaggcag gggttgcaat 317940 cctagtctct gttaaaacag actttaaacc aacaaagatc aaaagagaca aagaaggcca 318000 ttacataata gtaaagggat caattcaaca agaagagcta actatcctaa atatatatgc 318060 acccaataca ggagcaccca gattcataaa gcaagtcctt agtgacctac aaagagactt 318120 agactcccac acaataataa tgggagactt taacatccca ctgtcaacat tagacagatc 318180 aacgagacag aaaattaaca aggatatcca ggaactgaac tcagctctgc accaagcaga 318240 cctaatagac atctacagaa ctctccaccc caaatcaaca gattatacat tcttctcagc 318300 accacgccgg acttaatcca aaattgacca catagttgga agtaaaacac tcctcagcaa 318360 atgtaaaaga acagaaatta taacaaacta tctctcagac cacagtgcaa tcaaactaga 318420 actcaggatt aagaaactca ctcaaaaccg ctcaactaca tggaaactga acaacctgct 318480 cctgaatgac tactgggtac ataacgaaat gaaggcagaa ataaagatgt tctttgaaac 318540 caatgagaac aaagacacaa cataccagaa tctctgggac acattcaaag cagtgtgtag 318600 agggaacttt atagcactaa atgcccgcaa gagaaagcag gaaagatcta aaattgacac 318660 cctaacatca caattaaaag aactagagaa gcaagagcaa acacgttcaa aagctagcag 318720 aagacaagaa ataactaaga tcagagcaga actgaaggag atagagacac aaaaaaccct 318780 tcaaaaaatc aatgaatcta ggagctggtt ttttgaaaag atcaataaaa ctgatagact 318840 gctagcatga ctaataaaga agaaaagaga gaagaatcaa atagatgcaa taaaaaatga 318900 taaaggggat atcaccactg atcccacaga aatacaaact accatcagag aatactataa 318960 acacctctac acaaataaac tagaacatct agaagaaatg gataaattcc tcgacacata 319020 caccctccca agactaaacc aggaagaagc tgaatctctg aatagaccaa taataggctc 319080 tgaagttgag gcaataatta atagcttacc aatcaaaaaa aagtccagga ccagacggat 319140 tcacagctga attctaccag aggtacaagg aggagctggt accattcctt cggaaactat 319200 tccaatcaat agaaaaagag ggaatcctcc ctaactcatt ttatgaggcc agcatcatcc 319260 tgataccaaa gcctggcaga gacacaacaa aaaaagagaa ttttagacca atatccctga 319320 tgaacatcga tgcaaaaatc ctgagtaaaa tactggcaaa ccgaatccag cagcacatca 319380 aaaagcttat ccaccatggt caagtgggct tcatccctgg gatgcaaggc tggttcaaca 319440 tatgcaagtc aataaacata atccagcata taaacagaac caatgacaaa aaccacatga 319500 ttatctcaat agatgcagaa aaggcctttg acaaaattca acaacccttc atgctaaaaa 319560 ctctcaataa attaggtatt gatgggacct atctcaaaat aataagagct atctatgaca 319620 aacccacagc caatatcata ctgaatggac aaaacctggg agcattccct ttgaaaactg 319680 gcacaagaca gggatgccct ctctcaccac tcctattcaa catagtgttg gaagttctgg 319740 ttagggcaat caggcaggag aaggaaataa agggtattca attaggaaaa gaggaagtca 319800 aattgtccct gtttgcagat gacatgattg catatctaga aaactccatc gtctcagcgc 319860 aaaatctcct taagctgata agcagcttca gcaaagtctc aggatacaaa atcaatgtgc 319920 aaaaatcaca ggcattctta tacaccaata acagacaaac agagagccaa atcatgagtg 319980 aacttccatt cacaattgct tcaaaggaat aaaataccta agaatccaac ttacaaggga 320040 tgtgaaggac ctcttcaagg agaactacaa accactgctc aacaaaataa aagaagatac 320100 aaacaaatgc aagaacattc catgcttatg ggtaggaaga atcaatatca tgaaaatggc 320160 catactgccc aaggtaattt atagattcaa tgctatcccc atcaagctac caatgacttt 320220 cttcacagaa ttggaaaaaa ctactttaaa gttcatatgg aaccaaaaaa gagcccgcat 320280 tgccaagtca atcataagcc aaaagaacaa agctggaggc atcatgctac ctgacttcaa 320340 actatactac aaggccacag taacgaaaac agcatggtac tggtaccaaa acagagatat 320400 agaccaatgg aacagaacag agccctcaga aataatgcca tgtatctaca actgtctgat 320460 ctttgacaaa cctgagaaaa acaagaaatg gggaaaggat tccctattta ataaatggtg 320520 ctgggaaaac tggctagcca tatgtagaaa gctgaaactg gatcccttcc ttacacctta 320580 tacaaaaatt aattcaagat ggattaaaga cttaaatgtt agatcaaaaa ccataaaaac 320640 cctagaagaa aacctaggca ataccattca ggacataggc atgggcaagg acttcatgtc 320700 taaaacacca aaagcaatgg caacaaaagc caaaattgac aaatgggatc taattaaact 320760 aaagagcttc tgcacagcaa aagagaaact accatcagag tgaacaggca acctacagaa 320820 tgggagaaaa tctttgcaat ctactcattt gacaaagggc taatatccag aatctacaaa 320880 gaactcaaac aaatttacaa gaaaaaaaca aacaacacca tcaacaaatg ggcgaaggat 320940 atgaacagac acttctcaaa agaagacatt tatgcagcca acagacacat gaaaaaatgc 321000 tcatcatcac tggccatcag agaaatgcaa atcaaaacca caatgagata ccatctcaca 321060 ccagttagaa tggtgattat taagaagtca gggaaaaaca ggtgctggag aggatgtgga 321120 gaaataggaa gacttttaca ctgttggtgg gactgtaaac tagttcaacc attgtggaat 321180 tcagtgtggc gattcctcag ggatctagaa ctagaaatac catttgaccc agccatccca 321240 ttactgggta tatacccaaa ggattataaa tcatgctgct ataaagacac atgcacacgt 321300 atgtttattg cagcactatt cacaatagca aagacttgga accaacccaa atgtccaaca 321360 atgatctgga ttaagaaaat gtggcacata tataccatgg aatactatgc agccataaaa 321420 aaggatgagt tcatgtcctt tgtaaggaca tggatgaaac tggaaaccat cattgtgagc 321480 gaactatcac aaggacaaaa aaccaaacac cacatgttct cactcatagg tgggagttga 321540 acaatgagaa cacgtggaca caggaagggg aacatcacac accggggcct tttgtgtggt 321600 tggggagggg ggagggatgc attaggagat acacctaatg taaatgacga gttaatgggt 321660 gcagcacacc aacatggcac atgtatgcat atgtaacaaa cctgcccatt gtgcacatgt 321720 accctaaaac ttaaagtaca ataaaaataa ataaataaat aaataaataa atactagttt 321780 ggctgcattg ctttgatttt cttctttagg ggcctgttca tacatacaaa ggataccatt 321840 tacctgtctt ctatatgact ttctcttaaa tcctttcatt cttttgtttt aatttttatc 321900 ttcacatcct ttatttctgt cactgtgctg tccatagagt ttgtctgctg tgtgtcctta 321960 taattaagtc tatgttctga atgtttttcc ttttttagaa attcagttct aaagtgttta 322020 atttctcgta tttttttttc tgttgcctca ccatatcatt tctgagtttt ctgtttctga 322080 aatgtgcaac taactctttc caagcattga ccagattctt cagtcttttt aattcattct 322140 gaaataactg ggctacagtt tcatctgctt tgtggacaga agtgccacaa agagccgaat 322200 tgtcagtgca gacccacatg aatcatagat cttaacgagg tttttactaa cgactagcaa 322260 aggatacaag ctaaaaatgg gtacaagcaa acacagcatc attcatcact gtaaagactc 322320 tgaactatca catggaactt caaaaggatt cttcttcttt gctgcaatgt gttttgattt 322380 ttggagtgat agatgtttgc taactacgca cgtgacaaaa atttgcttag aggaagccat 322440 gttagttttg atgctactca actttgtatt ttgttagtca tgagatagaa agcctgtgag 322500 attacatgcc cttcttttag cagctgcatc ccataaaatt aaaaattcca gtttttttta 322560 aaccatgaac aatttagtca gacttaatat atcctattta aaacattctt agataagaac 322620 ttcctttgtt attttgctaa tatacaatcc caccaaatgt ctacaagaag ggctagttaa 322680 tcaatatacc aaagatcaaa tctatttata tgaaccacaa atacaaaaca taattataca 322740 tatataattt tatataattt aatttataat tatatacatt ttatagcagc aatcaaaact 322800 atcatgtatt ttgggatgaa tttaataaag aaatagcagg agctctgtag aaacaagtat 322860 gaacttctat tggaagacag taatatcata aaacattaaa aagaaagcta taccatgttt 322920 atggttagga agattcacta ttgaaaatac atcaattctt gacaaatcgg tctataaatt 322980 cagtgcgtgt ccaatcaata tatttagctc atttaaaatg tatatggaaa aggctaagta 323040 ccaaagataa tcaaatgctc ttggaagatg aaaattaaag ttgagagatg gggtaaaaaa 323100 ctataattca gttctaaagt cataaagcta taataattaa tacagtatgg cattggcata 323160 gaaataagca cattgactaa ataaatagaa aatacagttc agaaaccaaa ctctacattt 323220 atgaaaaact gacctatatc agaacgagca ttgagactac aggagaacag aggaactagt 323280 aagttaatgg tcctgacaca attgatatct acatagaaaa aaaaacttaa tccttcttta 323340 ctctatgtaa aaacaataat tccagatgaa tgtaggactt aatggagagc caaaactaaa 323400 acttttatag gaaaacatag aaaaatacct atctcagggt cgggaattag gtcttcaaca 323460 tggcaccaaa agtactaacc ataaaagaaa cattaataaa gtcaaccttt ttaaaatcaa 323520 caactttaat taaaaaacca gggccaggca cggtggctca cgcctgtaat cccaggaggc 323580 caaggcaggc agatcacgag gtcaggagat cgagaccagc ctggccaaca tggcaaaacc 323640 tcgtctctac taaaaatata aaaattagct gggcgtggtg gcgggtgcct gtagtcccag 323700 ctacttggga ggctgaggca ggagaatggt gtgaacctgg gaggcggagc ttgcagtgag 323760 ctgaaatcgt gccactgcac tccagcctgg gcaacagtgc gagactccat ctcaaaaaac 323820 aaaaacaaaa acaaaatcaa aacaaaaaac aaaacacagg ttgctggaaa aatggttact 323880 tatttttatt atgctttata aaatatacag ttatattatc aaacttcttt tgtaagaatc 323940 aaatattatg ctgagaatat ggcaagaaaa aagaaaacaa cctccaccac tcataatggc 324000 attcccttta cccaccatca actaagtcag gaacctgcgt cactttcaag ttttctgaaa 324060 tgtggactga aaatacttgt ggagggccct cacagatgca tttagaaatg gtatgttctg 324120 gaaaatggaa ctgaaatgtt ttagcgagag tcatgggccc aaaccttgaa atagaggttg 324180 gtggagtttt ctatagtatg taattacaac acaataagac tcaaaagcat ttcaataaag 324240 tgtggatgga agacaagata ctgcttcaag ggcttcatta gctttctgca gactggagct 324300 ctccaaggca tggggaggaa ccctgtttac ctttggttca gaatcagttt taaccatcat 324360 tgagggctag gtcagagtgc agcattaagt ccttgggaat acactgggtg gggaaagaaa 324420 agagagcaat gtttttctaa aagcccagaa atgggcttac tgtgtttacc agttgtttcc 324480 aggataatgt attgcagtgc caattgctga tgagatggta ggattatact tcagtccctg 324540 ctttacattt atttcttaaa gaagcttctg gtaaattaga gcaatagcat cggcttagtt 324600 tagtgttgtt ctgttggact aaggatatca gttctatccg tatggtcggg cctaaagcct 324660 gggaaatatt taatgaaggg agagaggggg agagagtgag catgcaaaag agagagagaa 324720 aaacaaataa caaaacaaaa accaagacat ttccctttat agtaagaatg atgaggaaaa 324780 catgtttagc catacaagat atcaagataa tctcttattt ctttcttgaa aatgcaagta 324840 caaatgcctg caaagataaa atatcctctg gatggagtgg aaaggttcac caggcctctg 324900 aaatcacgtg aatgatgttg cgctttgctg ttaatgaagc tcggtgcatt tttcatttca 324960 gtttctacta agcatttatg agctattacc cttcccttcc ctaaactgcg ttgtttttta 325020 aaaagcctta gaggcattcc ttctagaaaa taaaggtaag tgttaagtgg tgataatttg 325080 gtaataggtg tcatgcttgt ggttcataat gtgttaccct acacattttc tcaattatcc 325140 ctagaacagc tttttgagga tatgaagtta gaccttacaa agcacatctt tctgctggaa 325200 aaatgaggtt tatagtggtt aagtttagtt gcttatgatc acaaggctag agagtggccg 325260 gaatcaagac tcttcaccct gatttcagtg ctttttcact ccaccattaa tatttattgt 325320 tgataaataa tatcaacact ttcctaggtg tattagggtc atctagaggg acaagactaa 325380 taggatagat gtatatatga aaaggagttt attaaggagt attgactcac accatcacaa 325440 ggtgacgtcc cacaataggc catctgcaag ctgaggggca aggaagccag tctgagtccc 325500 aaaacctcaa aaatagggaa gctgacagtg cagccttcag tctgtggcca aaggcccaag 325560 agcccctggc aaaccactag tgtaggtcca agagtccaaa agctaaagga ttggagtcca 325620 atgtttgagg gcaggaagca tccgtcatgg gagaaagatg gaagccagaa gacagccagt 325680 ctagtccttc cacgttcctc tgcctgcttt tatcctagcc acgctggcat gatgatgaca 325740 tggtgcccgc ccagattgag gatgggtctc catcttccag ttcactgaca caaatgttaa 325800 tcttctttgg taataccctc acagacacac ccaaggacag cactttgcat ccttcaatac 325860 aatcaagttg gcactcaata ataaccatca caagtccaca ccttgtcaac ttgatcccac 325920 atacatctcc ttaaatcata catgatctcc aaatacagac aataatgtca taattacact 325980 gaacataata caactatcgt tcatacaacc agaaatgcac caattcccaa accaaatgtt 326040 attacataaa gttaacaaca cttaaatgct gatatgaagt caataaatac tttttttttt 326100 taaaagatgg agtcttgctt tgttgcccag gctggaatgc agtggtgcga tattggctca 326160 ctgcaacctc cgcctcctgg gttcaagcaa ttctctgcct cagcctcccg agtagctggg 326220 attacaggca cccaccgcca cacctggcta atttttgtat ttttagtaaa gacggggttt 326280 tgccatcctg gccaggctgg tcttgaactc ctgacctcgt gatccaccca cctcggcctc 326340 ccaaagtggt ggatcccaaa gtgatccacc caccttgacc tcccaggttg taagccacta 326400 aatcttatgt cacatgatac aggaaaaaga aaggaagtaa aatgaagata ttgtcttagt 326460 acaagtgtat acaggcagaa agatgttctt aacaaaataa ggaggaaata ctcatgacaa 326520 ttacagtaac ctggttgctg caactcatca catggtcgta gctgttattg atgactacct 326580 tcttctacaa cccattctgt tttccctttg cctctagcaa gtacctcagc aggtcatggt 326640 tctttacctg gtggagtgtc ccaaaccttc attcctgaag ggtctgggcc atttgtagtc 326700 ctgcctggat cgagttgttg tcatttttta ttgaccttaa tcacagggct tggtaatact 326760 aagagacacc ctaaggaatt tcctgtattc cacacatgtt cttccttacc ttcattatgg 326820 agtagtagac tgagttcatc ttgataggct aagtcagtca ccccagccaa cactaactcc 326880 tttcttagcc tgttgactta gaggtaggag gagcccgaga ttgcaatctt aatttccagt 326940 ttaatgaaat cattattgtg tctcctggtg gcaacattca tcgccctgga actgagactt 327000 ctaggccagc agaacgtaat gctgtggaac aagaagcaca aattttacta gcgggtctct 327060 aggggtgatg gtgagtggtg ccacttccat ttccacccct tgattcctgg acccatgaat 327120 cctggctatg ggagaaacag taccaaatac tggacactga tccggagcat acacagcctt 327180 ctggaaaact ttgccccagc cctgcaaagt attgtcgcct agttggcatt gtaattgtga 327240 cttcaaaagg ccattccacc gttctatcaa tccggctgct tcaggatgat ggggaacagg 327300 gtaagaccag tgaattccat gagcatgagc ccactgctgc acttctttag ccataaagtg 327360 agtgccttgt tcagaggcaa tgctgtgtgt aatgccatga cagtgggtaa agcattccat 327420 aagtccatgg atggtagtct tggcagaagc attgcctgca ggataggcaa acccatatct 327480 agagtaagtg cccattccag tgaagacaaa ccactgttct ttctgtgatg gaagaggttc 327540 agtataatca acctgccacc aagtagctgg ctgatcaccc cgaggaatgg tgccatatcg 327600 cggcctcagt gtttgtctct gctgctggca aattgggcac tcagttgtgg ctgtagccag 327660 gtcagccttg gtacgtggaa gtccatgttg ctgagcccgt gcgtaacctc catccctgcc 327720 accacagcca ctttgttcat gggcctattg ggcgatgaca atggtggctg gggaaagagg 327780 ctgagtggta tccacagaac gagtcatcca atccacttga ttattaaaat cctcctctgc 327840 tgaggtcatc ttttggtgag cactcacatg agatacaaat atcttcacag tttttgacca 327900 ctcagagagg tccatccatc cacatacctc ttccccaaat ttcattgtca tcagttttcc 327960 aatcatgctt ctttcaagtc cctgaccatc cagccaaacc attggctacc tcccatgaat 328020 cagtatataa tcacacatct tgccatttct ccttctaagc aaagtgcaca gccaggggca 328080 ctgctcaaag ttctgtgcat tgggaagatt tcccttcact gctgcccttc agggatgtcc 328140 tagaaagggg ctgtagtgct gcagctgtcc acttttgggt ggtgactgca tcatgcagag 328200 ccatctgtaa accaggccct tgtcttctct tcctctgtca gcttatcata gggaactccc 328260 catgaggcca tcagtgcagg ctgggggaga gaaggcaggg tggcaggagt ggggaccatg 328320 ggcatttgag ctacttcctc atgtaaagta cttgttccct caggacttgc ttgagcctga 328380 tcatgtatat accacttcca tttgatgatg gaatgctgct gtgcacaacc cactttatgg 328440 ctagatgggt caaaaagcat ctagttcatg ataggcaatt taggtagctt ggtgatttga 328500 tgacctgtag tcaaacatac agtttctacc aaagcacagt aacaggccaa gagttgtctc 328560 tcacaaggag agtagttatc tgcaggagat gcagggcctt gctccaaatt cctagaggcc 328620 tcccctgtga ttgacctata ggggcctgcc aagggctcca aacaacatcc ctatctgcca 328680 ttgacacttc aagcaccatt ggatctgcca ggtcatatgg cccaagtggc agagcagctt 328740 gccaagcatt ctggacctgt tgcagagcct tctcttctgg atcccactca aaactggaag 328800 cctttcaggt cacttgataa atgggctgga gtaacacacc caaatgagga atgtgttgcc 328860 tccaaaatcc aaataggcct gctaggcatt gtgcctcttt cttagttgta ggaggggcca 328920 aaggcagcaa cttatccttc atcttagaag gaatatcttg acagacccca caccactgga 328980 cccctagaag ttttactgag gtagaagttc cctaaatttt agtcaatttt atttcccaac 329040 ctctggcaca caagtgtctc accaataaat ccagtatgtt tgctacttct tgctcattgg 329100 atccaatcag cataatgtca tgaatataat ggaccagtgt gatatcttgt ggaagagaaa 329160 aactatcaag atctctccaa caagattatg acacaaagct ggagaatcga tatacccctg 329220 aggtaggaca gtaaaggtat attgctggcc ttgccagctg aaggcaaatt gcttctgctg 329280 ggccttatgg acaggaatgg agaaaaagcc atttgccaaa tcaatggttg cataccaggt 329340 accaggagat gtgttaattt gctcaagtaa tgaacccata tctggtccag cagctgcaat 329400 tggagtcacc gcttagttaa gcttacaata atccactgtc attttacaag atccatctgt 329460 cttctgcaca ggccaaacag gaaagttgaa cggggatgtg gtgggaatcg ccacccctgc 329520 atctttgaag tccttgatgg tggcactaac ttcctccagg gatgcaatgt tgtgtttgat 329580 ttactatttt tctaggtaga ggcagctgta atggcttcca tttggccttt cccaccataa 329640 tagccctcac cctaccagtc agggagccaa tgtgggggtt ctgccagctg ctaaatatgt 329700 ctatgccaat tatgcattct ggcactaggg aaatgaccac aggatgagtc tgggacccac 329760 cagccccact gtaagttgga cctgagctaa aattccatta attaactgat ctccaaaagc 329820 ccctacttta actggaggac cacgtgatgt tttgggtccc ctggaatcaa cgtcagctca 329880 gagccagtgt ccagttgtcc ctgaaatgtc tgattatttc cctttcccca gtgcacagtt 329940 accctggtaa aaggccagag gtctcctggg ggaaggatgg gagaaagagt cactgcataa 330000 attgtcagca atgtagtggg gtccttcctc aaggggaccc agcctcccct tcattcaagg 330060 ggttctgggt ctataaactg gttcaagtct gcaaattgat tgaggggccg tgattctttg 330120 tataattttt aatttaaatt agtcttttgt ctacttgacc tggaagtttt ctgcttatat 330180 aaattaagca agaatgcagt aggcctcttg tcaatttcac tttttaggaa cactgagatt 330240 aagtagccaa tgccagagct ctacacaagt cagactattc tgattgttgc cttgcctccg 330300 ctgaccttta cggtaattgc acccaccttg ccttgatgct tgagtgccac cacttggccc 330360 atgccacctc aggatccaat tattaccatt gtatttaaat tttgtagttg aatgactgtg 330420 gttcccacta taatatctag catgcagaga agagcaatca cagagctctt caaggatgca 330480 ggtgctgccc tcacaaatct atttcacaat gtgctggtca aaggtatatc ttctgtactc 330540 tcccagctgg gatgagtagg actaaagtga cgaattcact ccaccatccc agtctccata 330600 agcctttgga tcccttcctc tacattaaac caagggagat caggcatttc cagctcactc 330660 acagtgggcc accttttgat ctatatttca gctaaccaag caaataaact attagaacct 330720 tttttaactc tccaagctgc aacattaaat gcagaattcc tgcttagtgg gcccaaatca 330780 atcaattcag cctgatccaa ctttatgttc cttctaccat tagcccacac ccttaatatc 330840 cattcccatg cctgttctcc agatttctgc ttatataaat tagaaaactc aagcagttct 330900 tttggagtgt agcgcacctc cttgtgggtc acattctgaa cctcatctct aaggggcctg 330960 ccgggacttt agtctagttc tataactata agcaaacagg ggtattgagg gtgggtcctt 331020 aggagaatca acatcgtctt tcctggcaac tgcctcaagg gaggtcatcg ctgatgcctt 331080 aggcagtgca gggttaaact cctcagacaa aggtgaaaag cctgatggca gcgcaggtgg 331140 aggaggggat gttgcctccc ctctgttgcc tgtttcctct ggtaaaaaag attcatcaga 331200 atttagaagc tcagtgcccc cagccttatc agggtcctcc cgcatggccc cattccaagt 331260 tgcagggtac cattcttttt caatcaatgc tgtcacttta acagtaaaca cctggcaagg 331320 ctgtgcacgt acctttcgtt gcaggtcagc cactcacatg ataagagctt gtgtctgatt 331380 ttccgcaatt tcagctcttt ctctacagga gataagactc gaacccaggg caatcttaga 331440 agatttgagg ctcagaatgt ggttctggag ctgggagata gaatccctga gttcatcatt 331500 tttttgtttt catcactttg attagtgaac ttaggagcaa ccaactagct tcattatatt 331560 ccttggttct ccacatatgg ttaaaggtat taggtataaa gtcactaaac tccttgcctc 331620 tcatgagcag tgaatcagga gtatcagatg catttatttt gcataactct ctacacagtt 331680 cacagcaagg actatcagtg ttctccacac tattagaagt agagtcccta gcattttggc 331740 gtctaatcat atttagcagc caactccaga aaccccaaaa ccatctaaag aaatccatcc 331800 gtaaaattct gttcctctag aaccactcct ggtaccaaaa tctgtattag tcaggattcg 331860 ctagagggac aggactcaca ggtgagatgt atatataaaa ggcagtttat taaggagaat 331920 tgactcacac aatcacaagg tgaagtccca caatagtctg caagctgagg agcaaggaag 331980 ccagtccaag tcccaaaacc tcaaaactag ggaagccgac agtgcggcct tcagtctctg 332040 gctgacagcc tgagggcccc tggcaaacca ctggtgtagg tctaagagtt caaaagctga 332100 agaacttgta gtccaatgtt cgaggccagg aagcatccag cacaggagaa agatggaagc 332160 cggaagactt agccagtcta gtccttccat gttcctctgc ctgtttttgt cctagccatg 332220 ctggcagctg attagatggt gcccacccag attgaggatg ggtctctatc ttccagtcca 332280 ctgactcaaa tgttaatctc ctttgacaac accctcacag actcactcag gaacaatact 332340 ttgcatcctt caattcaatc acattgacac tcagtattaa ccatcaccct aggctttagg 332400 gatataggga aaaacatgac tcattgctgt tatctgagag tacataatct attggaagaa 332460 aggaaaacag ttacatgtaa ggcttatatc agtataaatt agataactgc caagtgagag 332520 aggtagaggt agcaagtgct gtctgtgggt gcatgttaac tcagtcttaa tcttggaaga 332580 agtggcagtg tggaatggta catggagaag cagaagggac aattactgtg agcagatgaa 332640 tggctcacta caggggcatg ggaagaagat gcaagagcag tggaatcttt aattgacgaa 332700 cctggtacca agctgccaag tcttagtctc aggactggca ccgtgcactt ggccattgaa 332760 aagactttgg aacctgtgga gtgaagagtt gtaggaattt tcaaagcctc agtgtaggaa 332820 caatgtgaga atcaaccagg gcatggtact ccacactgtg ttcagatcca ctggtgttag 332880 gggagtccca gagaggcctc ttagagggtt gaggaggatg ggatcaggca tagcagagac 332940 tagggacacg aggctctgcg gccagactgc aggtctgcta ccaactacag tgtgattttg 333000 cctagtcaca taatctctgt gggcctcagt tttttgtttt ttgttttttt ctattacaac 333060 agtacctttc tcgtggagtt gtagtgatta gatatctagt accaagacta tgcttgttag 333120 cactgagtaa gaactcaatg aaggttagct ttcattggta ctatattact attgttagtg 333180 ttggtggtgg agctgaatcg cctaacctat gaggttggtg ctgaaatgaa gaaaagaata 333240 acagtgtttt aagaagtttg gtcactagaa gtggagctta gtaattaaag aaaaagagtg 333300 aacactttta ccttcttgtg gaagttagta agtctacaaa atgttaattc tgcatttgaa 333360 tgatcatttg ggagactctt attgtcctat ttgcactgaa aaagtcactg aatcattatt 333420 ttagaactgg aataacacct gagatctagg ccagcacttt gcaagttgtg ctctatggga 333480 cttttcatgg aagtggctga ggagttgcct tgaaggaagg cagagggagt gggtcttggg 333540 acacccttcc agttataaaa caggacgttg attctgtttt gtagttgcag catcacatat 333600 aatttcattt attaagagga tcccacttct aaaaataagt tgaaaaccag tgatttaatc 333660 cagcctctct gtttgcatat gaggaaatgg aattccggaa aggttaggtg atttgtccaa 333720 ggttgcagac tagactattt attaatagag tagggtcagg aacaaaagcc tgctccttgc 333780 tggtccagcg cctgttacta gttacataat gaatgctacc tattgctgca cagtgccaaa 333840 tcattgcact tttcagattt tactctaatc aaaagaaaaa aattaaagtg cacttccaaa 333900 tcagtactta tatgcaagag cttcaagaaa caaactagta tttaacttgg tggttacata 333960 ttgactgtat tttcattgag tgaggttaga agagattgag aagcgtgaaa tgaagttaca 334020 aagtagaaac tatatggtga actcaaggca aagattgtcc atagtaaaag aagacaaaat 334080 aagaatgaaa gagacaaaag aattgccaat gagttgtaat cttaaaagaa agatatattt 334140 aataaaatag gattgattgt tttgaatgtg ggctgagaag tcctgccatc ttccattgac 334200 tctgctcaca ggccttgttt gtgaactggc ttccatggat agcattactc tcctgacagc 334260 tgcagctcca aattcagcat gaaaaggctg gcaattctaa gaggaaggga gggtttaggc 334320 cacttttaat tctactttgt cattgcaagt ttcttgcatt gtttggcatt tgttggtctt 334380 ccttactgga tttcaaaact agaacacttt ttcctagcct tggaaccaac cacgaaaata 334440 accacctctt accctcatga agaacacttt aagtttttct cttttaaaaa tgaagtctgg 334500 aatatctcca aacatcttgt cactcacgcc ttcatttaaa tgtcaccctc tcaaccacaa 334560 ggaaactaaa attgccccct acttgctact ccctgtttta ttttctagta gaacatacta 334620 cagttggaga tcatctcatc catgtctttt attcttgtct cttatttgcc tctgcttgac 334680 tgtaagctca tggaaagtaa gggaccttca ccaactagca aagtgcttag gacctagtaa 334740 gaacctggtc aattctaact gagtgaatga ctgaattcct gtgagaagtc aacatgaaaa 334800 ttcctaggtc attagtttag ttattggaac tccaacactg tattggaaaa gtgtcatgga 334860 aaggatagtt agtggattaa ggttttttat aagaggaaga gggaaagaaa ggcattgtct 334920 ttacttcagg catttcaatg gccatgatgg agcctaaata ttgtatgttg cattttgttt 334980 tggttttgtg tgcacaagag ctttgccagt ggaatgaacg ggttaagaaa tgtgagtttt 335040 cttttcgtcc tgctatagag acttaaggaa ttgccctgtg tgagttcctt gagggcagag 335100 aaaaatacaa atccatgaat acctgaaagc cctgatttgg cccctaagca atctatgcat 335160 gtaacaacat tgcatttgta ccctgtacat ttataaacat tttaagaaaa gtataagaga 335220 aacacaaatt ttggttactc ctctctgaaa actgctctga tgtcgcttgg ccgggggaat 335280 taagacctct tcctgtggcc tgtggccact atgtgctccc ggctctccag gctcatccag 335340 ggccactgtg cctggggtca cagggttcca ggatgtcaac cttctttcag cttctctgac 335400 tcctcaagca tttttttttt tttttttttt tttttttggt ttccaagacc caaacgcatg 335460 tctctcttct tggcacactc ttcccaactt ttttcctggc taattgctag ttatttagtt 335520 tgagattaaa tgtcactccc tcggcctggc gcggtggctc acgcctgtaa tcccagcact 335580 ttcggacgcc gaggcaggtg gaccacgagg tcaagagatc gagaccatcc tggccaacat 335640 ggtgaaaccc cgtctctatt aaaaatacaa aaaaatttag ccaggcgtgg tggcatgtgc 335700 ctgaagtccc agttactcgg gaggctgagg caggggaatt gcttgaggag gatattgcag 335760 tgagctggat cgcacctctg cactccagcc tggagacaaa gtgtgacacc atctcaaaaa 335820 aaaaaaaaaa aaaaaaagtc actcactcac agagggcttc tcagatactc ccctgccccc 335880 tcatttaagt tgcaccgctt gttgtattct cttataagcc ccattctttt tcttcttggc 335940 attgatcaaa ttaacagctt tattttattt tagcattgtg agtgtatatg tgtgtttaat 336000 gtctgcttcc tgactaaact gtaccctgca ggaaggcaaa actgtgtctg tgttgctcat 336060 tgttaaacct tcagcactga actcagtgcc tcgaacatag gagattccaa ctcaatattt 336120 actgcgtgaa ggaatgaatg aatctttatg tccctcgtgc ctaacataaa gtctgccata 336180 tacaatggac taaaaaatag tattcagcta aaactgagtt acggagaaga tgaagtatta 336240 attgtatttt ttacagagaa acaatggtca gtgtatcaaa aatagagacc ctgctctcag 336300 atatataaca tagaactctc ttcattcatt tgccttcatt ttagttaaca gaatctgttc 336360 atctaagtag agcagagaaa aacttcataa ttgctgtgtc tgtgttattc caaaacattt 336420 aaacaaaagg tgaataactg aggtattctt ccctgtggta catacttgat gtgggcattt 336480 taaaagattg atcaaatctc ctttcagctg gatatttgag taggcacaac cattacagaa 336540 ttttcctcta gggacttact ttagctctta aactatgtaa actgaacaag caaactcaag 336600 tggatcatta tctatagaag tatagaattc catctccctt tggcaaacca ttcaaaccca 336660 gaagtgtgtt ttacacattc tgacagaagc atctgtaata accaactcta acctcctttc 336720 ttaccacttt agcacccaaa agtataagaa aagaggacat gttaaggctt gttctattta 336780 ttagaaaata tataaagagt tcttggctta agaactcttc tggctatcag ctccctgatg 336840 tgaaaaaagt aaatagcaag gggtagcatg gagtcttact cccgtgtgac agacagctta 336900 agaaagacaa ttggacatca tgtgactaca tgattcaagc taaagtccag acacatcttt 336960 tccataggcc aattgaacat tttctctgta atttccacaa taaccatttg caccagcatg 337020 aatggagagg gtctgagttc ttctgggtga gtaaagggtg tgtcagttat ctgtcctctg 337080 tcaccaggat ttagaggcag gctcatagtg actcttgtaa agttgaggtt cgcctgtgga 337140 ggctgcaaaa aagagggagg aagagagagt gaggttcctc ttggctctgt gccagggatg 337200 tgattagagg accctgggag ggccttcatc ctacgagggg ttggaagtgg aaatggatgt 337260 gtgtggatga cctggtaacg tgtcacagcc ccttccaccc catagtagtc agggatttaa 337320 tgcctcaaca aggcaggtct ctgaaggaga ctgacttttc tctctctctc tgaatgatac 337380 tgcctgagag aaatactcac ttcctgcttt gttttcaaca agtatggact tccttacaca 337440 aaaagaatct tttttgcttt tgtcccccca tttcactgga aatctatcca ctgggcacca 337500 ctgttggtcg gcttcctttc atagattcct ttatgtttca aattttaaaa agacaataat 337560 agcaacaaag tgaaatatgg atttaagcta ggaaaagcag agaactgaaa cttttttcct 337620 gcaatcatac ttcccagctt cttcagcaag atctgcttgg ctgggaacat gccttctgag 337680 aactttacat ttctaaactg ctgctaaatt gctccatgca tttattcctc aaactctcag 337740 ggaagatagc actggctttc agtctcatac caaccattct taaggtaatg gaccaaaagt 337800 catttccact tgaaatataa tccttctaaa tgaatcatgc aacatggttt ttacctccat 337860 tttttcagaa taactctaag atgatgatcc tctggccata ttttaaaaat ttctcttatt 337920 tgttttaatt ttcttccatt ttttctttaa ttttgtatcc agacactgcc ttctctaaga 337980 ggaatgacat ttttgcgggt tatcatgata tatttttagc ccatttgcct tgacccatag 338040 cttacaacag ttaaagaaca ctaacatata aacatagagt tttgcccaag gccattagct 338100 ttgcatgtta acaagtgggc agaaggaagg ctgggcatga gagagacatg ctgtccttct 338160 ggtgagatca tcaatcccat tcttgtaacc ttcagatcat tgcatttgtt cagaatcgtc 338220 tgcagaggaa aacatctcaa agttgggagg ttgttgaaga gtcagaaaca aatgggtcct 338280 gggtaatttt tcaaaacagg ctttttgtca attgtcagtc agctgtttaa tattgtcaat 338340 tgtcactcag ctgtttaata ttgtgctttg ttataaggat aggcactgtg gtctcagcgt 338400 tcttaagctt ttacatttcc gttatttggt tttacttctg cattagtaga gtagatgtag 338460 agtagatgcc acctctagga actctaccag cagcagcatc ttagactaga agctccctct 338520 ctaggactat aatctctgta gcctccactt ctcccacccc ttatttcttc tgagcctact 338580 tggtctttga tacttactat aatactttct attctcttat cataaacagt tttctgattt 338640 cattttcctc tggtttcata ctaagcccca taatcagtca ctgcaagatt accttctaga 338700 atttctgtgc cctcaagttt tctccatatc tagagagtca gtcatctgcc ttgagccaca 338760 tccactgtct actttcttca cttccatccc caggctgccc agcactgatg aaaacaaaac 338820 aaaaacaaac aagcaaacaa aaacaaaaac aaaaaactga ctaggatctc aatctggttt 338880 gcaaatccat gcttctcttt cttgacttct ttagacatca acagaattga cgcctcctct 338940 tgacctggga cacccctcct ccttggtgct ttcttctacc tccccctgct tctctgtatg 339000 tcttttgcag gctcatcttt ctcttaggct gtcttccccc atctctcctc tccctctgtg 339060 cactcaggca gtctcccttg tcaaccccca aaactgcttc tccagacccc agtgtttctc 339120 tgagctccag gtccacaatt ctctaaggtc catgtggatg tccctcacca tttcaaactt 339180 ctcttccaca gggagtccct ggttttcact accatagcat attaaaatac catgcatttc 339240 ccttcatacc actaattaca actttgtttc ttttttttaa attttatgtt ttaaaaatta 339300 tcttctgccc acatatattg taagctcctt ttgagaaaga cacattgctg tcctggtcat 339360 tactatattc ttatcaacta gcaggggccg tggtcggggc ttgtgttagt ccattttgtg 339420 ctgctataaa ggaatacctg atgccaggta atttataaag aaaataggtt ttatttggct 339480 gagggttttg caaactgtac aagaagcatg gcgccagcat ctacttctgg tgaggcctga 339540 agcagctttt actcatggtg gaaggcaaag agagagcagg cgtttcacac agcaaaggag 339600 agagcaagag agatgccagg ctccttaaac gacctgctct cccataaact gaaagagcaa 339660 gaactcactc attacggtag gatggcacca aaacagttgt gagggatcca ccccgaacac 339720 ctcccaccat gccccacctc caacactggg atcaaatttc aatgtgagat ttggagggaa 339780 cacacatcta ccctttatca gtgctcaata agctcgctga atgtagaaca gtgatataag 339840 gcaggggtgg gccaagtata ggcgacagga caaatttggc ctgctactgc ttttgtaaat 339900 aaagttttat ttatttacaa aataaataaa taaatacagt cataatcatt ggttacattt 339960 tgttcaaagc tgcttttgca ttaaaacatc agagttgagt agctgccaca gagactgtaa 340020 tggccccaca aagcctaaaa tagttacccc gtggtctttt acagaaaaag tctgatataa 340080 aggacagtct cacagcacag aggaaaagca tataacccaa aggaggaaag agtagagcat 340140 agtggactgc agagaagttt ccctggaccc aatctgtgcc ttgaaagatg agaaggacac 340200 ctccaaaggc aggatggggg tgaggtgggg tgggcggtgg tgatccaagc agacagcacg 340260 ggcaagtgtt ctggaaaact tgcctttgtt cacaagtatc ctgcagtata aattgcaagg 340320 tgggcagtaa gaaatggact tgaagagatt gaacaagggc cagaaaccca aggacattgc 340380 taaggagttt gtgccttagc ccatccaggg ccctagcagc cttgactgat gcttctgagg 340440 tcctggaggc tccaggctca ggctaccttc ccatattctc tgaaaataat atcacatttg 340500 tttagtaaaa aaattgttta ctaaaaaatt aacctctcag aatttctgca ttcacattta 340560 tttcttctca tatcctcgag ttagaaaaag gtatttctct cctgtgatga tattgattct 340620 gcactcatct attttcatta ctgtctcctt ccctccctcc ctcagtccct cccttagtct 340680 atctcactct accatctttt cctttggacc ttctgacatt caacatcttg gtcgctccta 340740 tccagccaca cctctgacca ttcaaccatt tgtcctcttg attggttcca ccttgtccta 340800 tcacgctgga tatgctgttg ctcccaaatt gcctccctct gccagtttct tgccccttcc 340860 tccttctgtc tctccctctc tctttcaatc tttctctccc tcagtctctc tttctctttc 340920 cctctctctc aatctttctc ttcctcagtc tctctcccat tctctttctc tttctctcaa 340980 tctctctctt cctctctctc ttatcctctc tttctctcaa tccctctctc cctctttctc 341040 tctctcaatc tgtttctctg ttaatctctc tttctctctc cttctttctg tctctgtctc 341100 tgtctgcctc tctctctctc tctctcttcc ctagtgagct cacttgcttt cccagtttca 341160 gtgatttcta ttcagatatc tccaaaattt gtatttccgg atattttatg ctttcatgga 341220 ggccgtgtaa attggtataa cctttttgga aggcgttttg gcaatactta gtaaaaggtt 341280 aaatgtttac accccttgat tctgctattg tatgtgtaag gattttttcc tgcatacttt 341340 tgtaagtgta gaaaatatat gtataggaat aattgcacat tgtttgttgt agctgaaaat 341400 tacaaataat ataaatgcct ataatcagag cagttaaata catatgaaca cagtgaaata 341460 ccaggcactc atttaaaaga tgaggtatat tttaacaagc ctatttgaaa agatacccaa 341520 tcttagcaag tgaaaaaaaa actcatcaaa ttgatatatt tagcgctgtc cctctctcaa 341580 gtttcagacc cacattttca attttctgtt gtcatcttga cttagtctcg tgaaatttta 341640 aactaatcat ttttaaggga agatattttc ttcccttaaa gatgaaattc agacaaacct 341700 ctgaatttcc ctctttctgc taatttcttg ctttctttta tcatctttcc atccatccta 341760 acatacagtt ccagaggagt ctttaaatcc ttccttattg cctaacaccg aggatcattt 341820 gctgaaatct tgttgatttt tccctcagat caacaaagga ttttcagaat agccctgatt 341880 tctctttatc accacggtgc tgtctcacgt cttctctccc cctcctccta cctgccgtct 341940 cttccagact cgtctctctc ccccaatctc ctttgcgcac tgatgccaaa ttagtcacaa 342000 caaaagtgtt tacgtgatcg tgtcacccac tggtaagctc ttaatggtct tcccttacac 342060 attatctccc atttcatctc aggagccttt tattaaccac tcttcacagt ctgactcagc 342120 cctctttgcc agtttctctc tttacaaata gcaaagtcta tgagctagat tactcaatat 342180 tccctgaata ggtcttctct tctcccacct cttggccttt ccagtaccat tcaatcttcc 342240 tggaaattcc tgaaatttct ttcctcctca ctcagtcaat gttttgagac ccacatcaaa 342300 tgctacatac tatttgttcc tttactgatc atgccagttg gaaatgattc gaatctgtaa 342360 agcagggtgc tatggaatga catttcttat agccctttgg tcatttggga gcaatgtcta 342420 acataatatc ctccaggtcc atccatgttg ttgcaagcga caggatttcc ttcttgttaa 342480 agggtgagta gcattccatt gtacatatat tccatatttt attttttttt gctcatctgt 342540 tgatggtcac ccaggttgat tccatatctt ggctattgtg aataatgcta cagtgaactt 342600 gggagtgcag atatctcttc aacatattga tttcatctcc tttggatata tacccagtag 342660 tgggattatt ggatcaaatg gtaattatat ttctaatttt gggcagggtc ctctgtagta 342720 gctccataat ggttgtagta atttacatat ccaaccaagc acgccagggt tcacttttcc 342780 tcatgtcctc gccgacaagc ctgatattct tatttgcctc ttagcgcttc agcctttccc 342840 tcgtgactta acggtgactc ccttgagact acttgaaata ataagtttgg atggcaagga 342900 aatacccttc tgctgtcacc ctttgccata agactgagtt actttgtaaa caaagaagat 342960 ttacttggtc ttccatgccc aagacccttt tacttttcat cgcttaatat ttcatggcca 343020 aaaactgttg gttcttccaa tcttgtaagg ccatttatct ttgatcttgc tccattccct 343080 tccatttttg cttgagaatc attcagttct tgcctgatct cacgtctttc tcgcaacacc 343140 ttactaatga ctgccagagt gtccactaca cactatcggt ctcatttgac cacttcccca 343200 ggcatgtagc ctacctgcca agttctttca cagcagatat tttgcagtgt tgtaagaggg 343260 ctccctagct tgctatgttt tcttactacc tggcattagg aagtaaacat ttttcatggc 343320 agtattcact tctagtacca atttcttttt taatctacat gggctaactg ctgtatcaaa 343380 cagccatcaa atcccaatgt taattgcaac ttacagtacg ttgtgatgtt tctgtctgta 343440 tactcattca gacacacaga gtttaagtaa tttgttcaag atcacaaagt tagtaaatgg 343500 tggcatcaag atttgaaccc aggcagctgg actcaagagt ctaaacaact ttcattttaa 343560 aattttcatc tttcaagata tatcacttac aatttccatc ttcatcactt tcttccatac 343620 ttcagagctg catatgtaaa cctcttgatc atataaatat ttatggagtc tcagcatttt 343680 gagcacatgc tgagagattt tgtagcattg aagataaaga agctctttca atacatctaa 343740 tcttgccact attgattttg aacagcatct taatttgtta cctttttaaa accatattgt 343800 acttttcttc aggacagcta aattaaatgt cttatgttga tcccctgggt tttctcagtt 343860 tccatttatc agtttccttt tatataaaga gatgctaatg ggtaacctta cattttgtaa 343920 ggcatatttt tgaagatata caagtgaagg tttgatctgt acaccctcgt tagagctctt 343980 tattttacat gtggaggaag agatgcctta gggcttctga aaaacaggct tttattttta 344040 tagaggagaa acttccagaa catgccatga gcaaatgctc tgtcaagtct ggttctttcc 344100 cccattactt aagtgcaaat ggaccacatt tgaagaagat aagtagcaga acaaggctcc 344160 ccacaagggg attttgaggt gctctgaaaa ccagactgac ataatccatg gaggagttca 344220 tcactgcagg ctgtcacgtc tcacagtggg agtcataggc tggtctgctt gataaactac 344280 tcctgatcta tgactggagc tgtgtgcttc ctttaaaaat aaatcttgtt tttccatgcc 344340 ccacgtgctt ctcagcctca ggagcacctc atggatttag actaatcttg tcttttacag 344400 tcatgttact tccagattcc taggaatcac cccatttctg atgccgttga tccatccata 344460 cccactgaaa ttgagctaaa tgctctagtc tgatttgccc cttgaagtta gtatagaata 344520 ttttggctag actttgaaaa tgaagccctg accacaatgc ataatgacct cagtagacac 344580 tgaagagttc ctttgcatca ggcaagtgac aagtatctat ctcatcttca aagtccacat 344640 agatatgtgc cagattgtag gttgacaaat cactttttca ctagctcacg tggcaagcct 344700 tttcaccttg taataatgct agtgagagac ccataggtac cacataattg gccagtcatt 344760 gagattcaag caacatttgg ataatttagc aaaactatca tcagaatcat caaagtacat 344820 aatttttatt tattatgcaa atagtggatt cactaaagtg cttagaccaa ttaagttgct 344880 cccattgaaa aacagggtga ttttattctt aagaatatat caggataaac ttcttgtagc 344940 ctctaaacag tactgcttag aaaagtgcag cttcactgca ttgcatatcc ccccagaagc 345000 cctcaaagtt cagatgtaca ccacaaaaac atgaagcaca tgtgtttgca tggaaggtag 345060 gctctggggt cttcctatca taatatgtct atgattaata gtcaacatat gccccctcca 345120 cattccctaa aggaacatac acatgcatac acacacacac acacacacac acacacacac 345180 acgtgagaac tgaattgaga gtttggggta tacaccatcc ctgagggcac agtctacagc 345240 tcctaatgtg tgctgtagag caagcattat attgttgaca ggtaataatt cctggttagg 345300 aataacagga taccagtgag aagaggctga gaaaaataca ctcttgctgg aagagtcaag 345360 aacgagctct tcgtgggaaa ctatgggaga cgattgaaaa aggacaagaa gaaaggagaa 345420 ttgttaagtc tccactttct cagtttctga actgaacttt tgctcacagc aggtgaacac 345480 aggctccctc ccacactgag acttcctccc ctgccggtgt gcagtctgtt aagtaaacag 345540 agacgttata ctgagaaagg aacatttctc tattttggct atgagttgtt atttttaaag 345600 attcatcctc caaacatttt cccctatcct tgtttatttt ttcactagaa agaagatgaa 345660 ctgcttaaaa aaaaaattca actccatgac aagaaaaacc cacttctagt atgttctccc 345720 cactcaatgc caatggagcc tttggtgtga gcactctgcc agccacacat tgggcagcat 345780 acctcttgaa attcctgctg tgcttctata gagcttccat gcatccagat tttcaaagtc 345840 aaagcaaaat gcgcatggca gtttttttct gactccttca agttaaaagg ccaacctctc 345900 ccttgacata tccatgtatt tatcagtata tctataggta atacttaaag gtgatcctta 345960 ctgtgtgcca cactccattc taagcacttt acataaaaaa cctcatttca ctttatttgg 346020 gaataggatg acaatttctt caatattgag atgggttgaa tctggggaga ctgatgttag 346080 atgcaaaaag ctttctttct agaacttttc ctgtgtcttg cacctggctt tctccctgtc 346140 ttgttcccat tctagatctc tttactgaca gtgcccatgg ctttcttctt ggtactctag 346200 tgttgagcat aagaactagt atgtaatagg ctctcagtaa atcttgttga atgaattaaa 346260 gtagagcaag aattaaagac agagaagaag atcttcttgt tggagttctt tcttttggtt 346320 gataagcaat gtgatttgac gtaacaatct tgagtcctaa tcccctcatt tggaaaatgg 346380 aaataataat gctaatctta gaggtcactt ctaagaagta tatgaatata tcagaagtaa 346440 tcaacatttt taagtcaaag aaaagaacgt ctgtgaaaaa gaaaactaat gagctagttg 346500 aaaaaatatt aattggatct ttttctcata ccttacgcca aaataaatcc ccaaaaatgg 346560 ttgcacaaca ttgtgaatat actgaaatcc attgaatcac actctttaaa tgggcaaatg 346620 ttatgttatg tgattatctt tcaataaaat tgttataaaa atgaataaac cccagaagat 346680 caaaaattta aacataaaag catggaagta tactagaagg aaatataaga taattttata 346740 tgttatgttg tatatattta tatgtaaaat ttttttattt atttttcttt gcttttaaaa 346800 gcaagacata atgttctaga ggaataaatg aaacgttcga taaatttaat tctctattaa 346860 atgttttgca gaagaaaata ccaggaacaa catcagaaga aaaaacaaaa aaccataaga 346920 aaaacaatta aaaatacata tgacaaatgg cttattacta taatatttaa agaactctta 346980 aaaatctatg tgaaaatgac aaataacaga aaaatacgtg caaaggacaa gagcaggcag 347040 tttagagaaa gcctatacca atatattctc ttatcaacag tctattgtac aagctatttg 347100 aaagcaatgt ttgaactatc aaaatttaaa atacataagc ccttttatct agcaattcta 347160 cttccaagaa tttattctat agctatctgt acacatatcc aaagacataa acataaggat 347220 agtcattgaa tgaaatgttt ttaacaacaa aatacttgaa agcaaagaaa tgtcacccaa 347280 gaaagaagtg attgaagaaa gtttagcatt cagttcagtg aagacatatt gagctgtcaa 347340 aaaaagttga tggagaactc caaggtctat taactaaaaa caaaacaagg tgctaaacaa 347400 tatgtttagt gttcatattt taattgttta tatatttcac aaatatatat ttgtgcatgc 347460 agaaaatatt ttaacttctt tctaaccccg tcaaacacat catgccaaaa ttcaacttgt 347520 gataaagaaa aaaataaatg aattcctttc gtgtgtagta tctcatttaa attcttcaac 347580 aacccaataa aaaagataca gacacatgtt tttaagtact acatgttatg cacctttggt 347640 ttgcttattt aatagttgca actactaatg ttaaattctt gatgccaagg ttaaaagcct 347700 gaacttctaa aaatatcaag atctgacatt tttctgtttt cacagattaa tctgccatct 347760 cctgacctcc aacacactgc tctatgttct ttcatgctgc tcctcctccc atgtttagga 347820 ccctcttcca aggaggcatt cacatctctg cttgatgaaa ccctacatta tcttaaagcg 347880 tccactcgaa tgccacctac ttatatacca tctcctgcaa taccaatggg ctcagcccaa 347940 ccatagccca tagttattgt agttgttctt gtacttcaaa agcactacaa aacacaacca 348000 tcaggacttg ttacattatt tgaaggctat gagcatcttc agccgaggcc ctgtttttat 348060 tcccagaact accacattgt ttagaatata gtagcagatc aatatacgtg tattagataa 348120 atcgtttacc cagatcttga tcattttcaa ttacccatag gttgaagaac tccatattta 348180 acatggcaga cttgaggact gaactaccta cctcttctaa gaagttgaaa tgagaatgtt 348240 ttattgatgg gaaattattt ttttgttttg ccttctagaa ttcaaatgaa tgttcatatt 348300 ccatgaagac aatggctgat agttttttgt taaagattta gaaccagtgg atttttatga 348360 atgtgaaccc tttcatgtct tgtggaagat tttctgtttt ttaatctttt tatttattta 348420 tttatttttg ctatgttttc ataggaacca gggaaaatgt gtagagggca tggtggagat 348480 cttcgacatg ctgctggcta catcatctcg gttccgcatg atgaatctgc agggagagga 348540 gtttgtgtgc ctcaaatcta ttattttgct taattctggt gagttgataa cacaagataa 348600 ctcaatgctg gatgaaatgt ttatttgtag ttttcaacca gatacgatct acccactcca 348660 aaggcataat gtcataaata gaaagaaact actgacacac gttttaaaat aacctaccaa 348720 cattgcagat tccttataaa ggtagaacca tgctagccaa atagacacat gaaaaattgt 348780 aatttggcat tgaatcaaat ggcctttgag ctaaaatttt tgtatgcttt cacagatagg 348840 atgtttttat tcaaatggta catgtatata gacatatgtt agttgatagt tatattatgt 348900 ctgaaaataa gtagaccaag taattctgtt aagaaattgt gaccaattcc aggctccaga 348960 tagtaaagaa agagggttat ttgagacaga ccatgtttct ggtcaaaact gactagctaa 349020 aaatatagtt ggcttagaga tagaaaaacc tgtttctaaa acagaagaat gtggaatgca 349080 ataaattgtc cagctgaaag aacattttcc atttgctcta tgaagtctga ttctactgcc 349140 ccttcgtatt tatttgtttg agaaagctta gctaagagca acatctgttt tttgtttttg 349200 tttttgtttt tgttttgttt ttgttttcaa tgtagtgagg ctggctgttg tataaagagt 349260 tactctatgt caccaagatg gaaactatgg ttcagcctga attagtgccc tgactcctcc 349320 tagcctcttg gtatttggat ctaagctcta gctctacagc ctctgggacc taaagctcac 349380 attgggtatc agcggtacag cagctcccct taagctccac ctttccccct ggctctaacc 349440 ccactttgtg cctcatccct cattctcaca tagaaatcat agctatttcg aatctctggg 349500 cctgacttag tttcttatgc cattagacat agtctcaaat tcctcaatag ctgaattgca 349560 gcttgtattg atcacataca tagagaatcc gcacttcctt ctctttccac gtgtttttgt 349620 ctctttctga tgagtgctga tcccttcccg cttcccctaa caatttttta cttttcttcc 349680 ccaccactgc taggaacctg tgttgcttaa tggaatcagc ccttccttct cttttcttgt 349740 gtttttgtct ctttctgatg aatgccaatc ccttcccacc tcccatgaca attttccact 349800 tctcttcccc accaccacta gtaacctgtg ttgcctaatg gttatcacag taatcattct 349860 cacttatcaa ctaataaatg gaaatctgta ctattacact aggcaaggac tgaattacag 349920 aatgaagtcc catgataaat gatgtgatcc acactaagga agtgattacc actccattca 349980 ggtttctgtt tccactcacg tgcattgtgc ttttcatttc agtcgtttgt cctgtacatt 350040 gtagggtcca gatcccacaa tggctcttta ttggatgaga gttctgggag cagtgccact 350100 cagctacatg gtgccaggtc ctgaacctgt gccttcttcg gtggagggct ggcacgtgct 350160 gacagctttc atgtgggcaa tctgggaact tcagagaagg caggcctatt aagtgttaag 350220 actccccacc ccgaactttt actgagaaaa agtaccccag acaggaagta aaattagcca 350280 gagttgtatg atccacacag tggatgctct gatctcagta ataaaaaata tttcctccag 350340 atccatatag acttttcctg cattattgtt ttgtttctgt tcctatggca gagtgagttt 350400 ttaaaactat tatgcaagaa atatcaggat ttttgccacc aaaaagttgg attcatagac 350460 ccagggtttt tacaacccag ggggaaaaaa ctttcagccc tcacaagaaa gtattttatt 350520 aaagactggc acccaaacct caagactata tttctcactg caggatttgg cccctgtctg 350580 cctccttctc agactagtta aactttcata ctccatcctt gttccttcgc ttctttctta 350640 ggatcttctg tgcacttctt tcttaggatc ttcttggcac ttctttgctc ttgaagggca 350700 gaaacgctat tgtagaaatt caaggcactg tatgctgaca tagtttatag ttgtcttttt 350760 catgagataa cacagcggct ggcagctcct cttttctatc aaggacagta ctgctggctc 350820 aggagagcag taagcaaaca gaagctgtct ctcaaccctg tacaaagcga aaccactctt 350880 ttccctacaa aagtgagctg tgccccagaa aagcggatct gctgctgagc agggctcctc 350940 atgtctccta ttgttcctga aaaacagcat caaagagggc aagactgaca cacaatgttg 351000 tagcattagg agcctttttc agaataaaaa agcaatcagt catatgaagc atgtggtcat 351060 accacaatca acaatttttc tccacaactg gagatatgga tttttctaaa agtccaactg 351120 attcatggcc ctgatacggg gcagctctac ctctcatgag accaatgacc aagtgactct 351180 gactccagga atctctgaca gaagccaagc tggaaacggc tcaggaaacc tgagctagaa 351240 gatgcctttc tgacacctgg gaaacaaaac ctcagtgtat ggaggaaccc aaggttttgt 351300 gttgagcccc agtcgccaag gtctgaggag gctgggttta tattggcccc gattttgtgg 351360 ccgaggcaca aggggaattg aaaggttgtt gtgaggacct gctcggaatg tctttctgga 351420 agtttggaga gggtctctca aatgccaaaa tttccatggg aagccatttt cacagctgct 351480 tgggagtggg agatattcgt catcatttct gccccattta gaataattta ttactttgct 351540 tgcaaaaacc cggaatcatc cataggacac acgttgtttg tttttccact ccacaccaaa 351600 ggacagaggc attcctggtt aatccaagat gccaacttca agacattctg agaactagct 351660 ggacagagct gaagtgtagg gcaaatcaga acagaagtga tgggcccagg gcaaaagccc 351720 gtgaagcagc agctgcggag gaaggatggg agctggagct gcaaaggggg ccatggtgga 351780 gactctgggc ctgcccacag tatcccctct gcccaatggg aattcagttt tcctgcatat 351840 cattcaatta tttctcattt ttctaggcct agctcacctt attcgggaag ttttgcgact 351900 accccagtcc ataatgaatt tcctctctag actatttcaa ttcttacagt cactaccaca 351960 cagtctagga tttggttagt tggttgattt cattcattta ttcaataatt caatgtttat 352020 tgagttccta ctatggactt tgtgccaggt atacaaaact gaatgttact gttgtgtggg 352080 gtttttttct ttgcattttt aaagttaacc tggatttttc tctcactctt tatgcatgta 352140 tttcctaatc tccctataaa ctatttgtat ttttttggat tcctcacagt ctatttagcc 352200 tgtggactgt caacagatgt tacatcattc agtcatttaa tagatgctta tttgctagac 352260 atggccagga ggacctggaa agtcctcatt tttcccatct gttcttacca ttctgaaatg 352320 tatcatgctc ttcagtgctc cacagatcta gatgatatca aattattaaa tggaaaaagc 352380 aagacccatc tccttgggtt attgtggata agggggaaat tgtgtaggaa gtgtctattg 352440 cagttcatgg accattgtag gcccttagtc aacaacagct atcatcatca ctgatgagaa 352500 tctctggctt aaacggagta ggttcatgcc ttttttcagt gtaatgaagt gttttagttt 352560 aaaggccttt agcaaggctt acaataaaaa aaagtgggga ctccagggta acaccaacaa 352620 tagagacgac catggctgtt atcctgagac tattaattat gccacgtaat tagatttaga 352680 gaaaacttag agcaacattt atcttgtgga taataattga ttgtgattgg gacttaccgt 352740 tgagagaccc tgatgaaaac tctatggtga attgctgtgg agtcacatgg gttcatgcat 352800 cattcatcag tgggccctgg ttttagcctc ataacccctg agaatccacc tctatcagaa 352860 aaccaccctt tcagtgaaag ttcctcaagg ctcagaaaaa ttcatatgtc aaagctttat 352920 atgtaaaaac ctatactctc taataaatgt ttggtttggc cttcacattc aatttaataa 352980 ttatttctac ctcttttcta aaccgctctt aaccacagtt ctatatattt aattctgaag 353040 agcctcatgc acctccctcc ctggtaactt tatctacttc tctccctgga gaaccagcca 353100 gaccatgatt ccagccctct gtcctctctt caaccgtagg tcctcttttt ctctcctgac 353160 tcctcaaacc ttctccagtt acccggatgc cttctgtgtg ctgctggctt ctgcatcact 353220 gttcacaggg ccacttgttc ccctggaaat gtcttatgct cttgaaatgc tatagccttg 353280 ttcacctgtt catccaaaac tgatcctcag acaacatttc tctttcaatt ggtggaataa 353340 taaagaggaa tatgggtcaa aattcataga catttaaata cccaaggtgc aaagttaaga 353400 gaaaacaaga taggagaaag aattatggca acatctctaa aatgtgtact ttagtgttta 353460 gcaaaaaagg gactatggaa tgtcaaacag gaacatatat gttaaacata aacatgaagc 353520 agtgccagct gctgtctgcc atatagtcat gctttgttaa tgtggcacat cttgccatga 353580 tggtgccctc atgaaacgaa ggatgctgaa gcagatgcca ttctgtttgc tttgatcaga 353640 agccactctc tggtcaagga agtatttgtt tcatgcttaa ttataacaag ttctcatcac 353700 aaagattatt ttctttctcc agatctggat tgtttgcact cactttatat tattagacaa 353760 ttactcagat tgtttatgtt tttatgttta gaaataagac agtgattcag agagtccctg 353820 tatttagatg aaagaacatt ttttaaacat attgactgta aacactgaaa atcattaatt 353880 ctcaacagtt gaaggtttct gacaggaacg gcccttggaa attgtaaatg ggcacattgt 353940 caggtatgcc cattgttgtc acattggaga agattggatt ctgttctctc tggagtcctt 354000 tgtaatgcca agcttcctct ccagggagct ggcttattgt cattattttg agataaatgg 354060 cacttcatag tattaagtgg ttcattgtct cttctctggc tgactgtatt ctgtaggcag 354120 ccactcaact ttggagcctt tctctgctac caacttttgg tgttgcctta agcaagcctc 354180 atggctcctg ttagtttcct gacaacatgg tatagcatgg actttgtcat cagagaggac 354240 tgaattcagg agaagcaact ctgccacttc cttggcggaa gggggatgac tgatgtcctt 354300 tgataagctg cttccctgag cctaataaaa aaatagaaat aatgatactt aaactcatgg 354360 aattgttgtg acaattgaaa gaatgaccag ttagtaaagc atcttgcacc atgactagca 354420 cacagtagat gcacatgagt gttactaagc tttagttatg ccctccaaat acaaagcctt 354480 agttttgtca ctatgaaaga aattactctg ttcttcttag caggtaataa ataaatccct 354540 gcctggaaat tctgcaggag aatttcaccc ctgcgctttc aggttaaaag attgcattcc 354600 catgatgaag atgttctgtg aatagaatca tctcaagtcc caaatggtgt ggatttgctc 354660 ctgcatcttg ttgcagagat tctcttggag cttctgagaa ctggggaaac caacaaaatg 354720 cctgtagcct ggggaaaatg tagggagttt tagcatgaat ttgtgggagg tgagaaaagg 354780 cagcaggtgt cgaaagacgg gaaatccttg cactgttcta gatgttagga gccattttcc 354840 attcacattc agcacctcag gaggagaagc tgcctatcac tttgtgtcct caagagaacc 354900 aacaaaggag aatgccatct cccagatact caatttgatt accattttat cctaccttct 354960 ctagggtcca gacattatgt aaattggcat taagtttgaa taatgtatgg acccagttta 355020 aaaggaaaaa atgctttggg aggctgaggc aggtgcattg cctgaggtca ggagttccag 355080 aacagcctgg ccaacacagt gaaaccccat ctctactaaa aatacaaaaa gttagctggg 355140 cacggtggcg ggcacctgta atcccagcta ctcaggaggc taatgcagga gaatcacttg 355200 aacctgggag gcagaggttg cagtgagcca agatcgtgcc attgcactcc agcctgggtg 355260 atgagagcaa aactccatct caaaaaattt ttaaaacaaa aggaaaaaat gctcccctga 355320 ttcccgcagt gctgacttaa aatgttctta gtatgccaat gttgcttaaa tatgaatgac 355380 tgtagcttct acttaaattg gcaaccgcac caaatataaa ctgcaaatgt ttatagctct 355440 tatggaagta taaaagcaaa acaaattctt aaattaaata caaactaaga gggaaactga 355500 taataacaat gttttgtgta attaagttgc tgtttgcaac atgcctgggg cagactcctg 355560 gcctctttgc atctgacatg agaggctacc aaggatgtgg ccacaactgg gctctcccag 355620 cacttgcttg cgctcagaac tgtgccaaaa cctttgctcg cccagtgttc tgcaacgtcc 355680 atcatttgga tttggcagga acacatcatt tatgcatttt gtttgcttct gtatttagtt 355740 gagatactta aaatataact gctagattct aaggcattca taagcatctg tgaaaaatgt 355800 gttacttagg aaacagttca gggttccatg gattatctag attggtgagt cttaagactg 355860 accacacaat tcatctgggg gtgtggagga ggggagcttt gagaaaaatc tctgtatgag 355920 cacccacacc cagagattcc tatgcaatta tcccagagtg gtgccttaat atcaacattt 355980 gtttaaaacc atcccccaag actaaaattt gtgaccggga tttagaacca ttgacttaat 356040 tgatgcagaa cactctgata ttaatgtctt catgtctttt ggaatgtcat taagacaaaa 356100 gcataaaatt ttaaaattct taaagacaat ttaaagacct atgagaatcc atctttaatt 356160 ctcaggagcg tgtggaacct agtttgaaaa ctactggcat cgacaattga atttccacta 356220 aaataaaata gctctctagt atattacaaa actacccatt ctgcaaactg caggggagct 356280 actgataatg cttggaactg tgccaggcac tgcctgcata aaaatgagta aggtccactt 356340 cctccatgga ctgggttggg taggaggcaa agataattaa ccaattattt taatattatg 356400 agttcagggt tgtaatgaaa gtaagtattg agtgctgcag agacccagca aaggagtcct 356460 tagctgagaa ctgatccttt gctgagtgac gaggacatta ttgaaccgcc aggcttgatg 356520 gcatgttgca tggtaacaga ccagtacacc aaacagcagg agctgtagca gagaaagagt 356580 ttaataattg tgtggcagcc aaataaggag acagaaggaa accttaaatc cacctcttga 356640 aaaagtctgg gactaggctt tttaagagaa ttctggcaag aaggaggctg aggagctggg 356700 ggtaactgat tggttaggac ataggagagg agacaataag gatatagaaa ctccattctt 356760 gcactgggtc agttcctcgg agggggtcct cactctggct ggcagcagtg aacccattgg 356820 aatgcaggat ctgaaaaata tctcaaaatg gcaaacttga ggggtttttt ttagcatcaa 356880 agatgttatc tatagaagtt aggacattgt gacaggggct acgtgacttt gaagtgttaa 356940 gtggctgtca gaaagtgagc tattgcagcg gtccccaacc tttttggtac cagggaccag 357000 cttcatgaaa gaaaattttt ccacagatgg ggtggtgtag ggtggggtgg gggatagctt 357060 cgggatgaaa ctgatccacc tcagatcatc aggcattagt tagattctca tgaggggcac 357120 acagcccaga tccctcacat gggcagttca cagtagggtt cacagcccta tgaggttcta 357180 atgccactgc tgatctgaca ggtggcagag ctcaggcagt aatgcttcct tgcccaccac 357240 tcacctcttg ctgtgtggct cagttcctga cagattacgg actggtacca gtttgcaacc 357300 caggcagctg gggacctctg ggctgtaggg taggctggtt aatgcttagc tgtgtttcta 357360 ttcaaagctt atgcttttgt ttaaaaccta gtaatttggt tttgttaatt ttatgaagat 357420 gatttcaagg atgagtagga ttagctggag tcagaaggac acaagggaat ttctggcaac 357480 aacattaaac taccagtgaa tgtctcatca agtcactgga cctctaattc taagcagtac 357540 tgtcaacctt ataggttatg atgtataaga tagtgttgtg atgtataaga tagtgcaaaa 357600 acctaagtta atatcaccat ttctgtagta ctctctattt caaaggaaaa aatcttcagc 357660 agtctaatat cctaccaaaa ttttgaagtc aagacctccc tacactaatc aaagaactag 357720 aggtgcaatc aggccatata tttggaaagg ccataggtgc cctccctctg tccttgttcc 357780 cagcatacta aactatagtc taaaagactt taaaacttga actgaagaaa accttaagga 357840 aacaacaaca aaattccatt tatttcctga gcccaaaagt agaataattg ttttttaatg 357900 aatttttctt tccctgtaag acatactatg aattgttcaa tgggtattca aagcatatgt 357960 aatagaatat gtatgctttc ctgaaaaatt gaaatggaac atcaaactgt tctgtaaagt 358020 tttgagtcta gaccaaactc acagcactta gccagaatat gtacatctgc atctgccact 358080 catggcccca tcgctccctc caactgcttc tcttgggctg aaggatggaa aagcaaactc 358140 cctgcgttga gttccatctt gccctgcatg gcctccccca tggggtcatt gagctcccca 358200 ccagcttcca cctcttccag cactttccgc cagagggccc gtggctgctt ttgcagactg 358260 aaattgattg tggttgattc agctccattt cctctgagtt tttactttag atgtgctttt 358320 taggttgcat ttttcttctg gcatataaga aagacagcaa tattccatgg aacagagtga 358380 tgtctgtggc tttgtcaacc gttgtttgtt agcttgatca ccatttattg agtgtttact 358440 actttccagg cattgtgcta agtggtagaa atacaaagtt gcctttactt gattcatctg 358500 taaaatagag agagtagtag ttcctacagt gtggtttatg tgaggcatag ggactgctcc 358560 ctgaaaccta gggacaactc cctagcagcg acccagtgct catatcaata gtggtaacaa 358620 ttaggaaggc agctcctacc tcaaagacct catgatctga tggtaaagac agatataaca 358680 agaaaattat tctttttaaa tataaaattg tgatataaaa atagttttca ctaaattgga 358740 tttttatgaa atttacagaa acaaaataat aaattaagga aatataaaac cacctgacat 358800 tagccaacca tgttgatgtt ctgattatgt tactgcaaag gagtgtaggg ttaagaacga 358860 gggactttga ttccaagatc aaatcccttt ctgctatttc ttagctgtct gactttgggc 358920 aagttgctta aaccctttgt gcttctgtgt gcttgcccat gagatggaga ttataatagc 358980 gtctacctca tagggctatt tttaatacaa gttagctctt agaacaatac ctacttaaac 359040 taacaatttg tattaggtac tgttttattc tccatccgta ctgtgtatgc atatattcat 359100 atttatattt acatattcta attaggatta tatacatgta ctttctttaa aaataagatt 359160 ttaaataact atataatcag tcatgatgat acaacatgat ttattcaaca aatctgatgc 359220 tgttaaacac gtaagtgatt tctctttcag gattataaat aacatttgtt ttgcattttt 359280 ttcatacatc ttttgctcac ttttcattgt tactttgtat atgttgctag aaattgattt 359340 gctggtgaaa agggtataaa catttttaag gctcttgcta catattgcct gctcttcata 359400 catattgcct actgccccag gaaactatca attacacttt taccaagagt gtatgaaagc 359460 attcacatga atgtaacctt atcatgcaat gcgggccatg agacagagga gagttatgga 359520 gggtagacgg cttccccgct gctcagccac tgccctctcc tctaaaagag ccacagtcag 359580 gaatttctac atagatccta ttataaacat ctccttttga aacaaattat cttctctcag 359640 agcattttct tcattttagt atctatatag gtccttgtta tgttcatttt aagttttgtg 359700 acctgcactg acacaatgct gatgaactgc ttattccagg cagtctgagt tctcaaagca 359760 tttgcatttt atgtcttatc ctctgttttg ggctctttgc cactgatttt tttttaagtg 359820 atattttaag aaagaggagg gttgatttgt tgtgagtgta tctctcttta aaaacttttc 359880 tagggaagga caacctcttc caaagacttt gtttgctttg tgtgattggc atgtccttcc 359940 ctggtcagta atgagcttga aggaagctac tggacacggg actgaacatg gggttttgct 360000 atcactctag ctgtgccttt ctctagtgat caaggagatg ttggttcaga aagtgccctg 360060 tctaatccca ctaaggcccg aaggaccaag tgctgtctac tctccagatt ctctgcaaca 360120 gaaagcagat gcttaggctt catggtccag gttggaacag gtagttagct ctgaggacag 360180 ttatgcatga atgtcaggag gggactggca ggggaacatt tatttattct ttaaaattgg 360240 aatcaacagt tatggatgaa acccagaatg caaaattcac tttcatcttg acacgcaaca 360300 catctgtcct ttctccttga atagcaagta ttaatcattg agttagacaa tgtaaccttc 360360 acattcagtg aaagccaaac actcagcacc ttctagaaaa atcttagtgc catgctttct 360420 tagcatattg caagtcctct gaggatgatg tgttgttcag ctttgaagct gatcttttgt 360480 acttgcttat gtagctcagg ctagtgataa catgccagag gcatttccaa ctaagaaaat 360540 tattcacaga agctttaatt acaaatttgt tagccccact tcctgctaaa atggccagcc 360600 ttgaagagtt tcggaaatgt gagcagcctt aaggatgata gaaatattat gaaatagtaa 360660 taagtaatac ccatacagca aactcctttt tctttggagt atccgttcat cagccagatt 360720 tccctctcaa cagtccaggt gttgacgaag atcatgaaat aataggaatg aaagggactt 360780 cgattttgta tttttaatag cattttcctc caccaaatta cgaaagtaat gcatgaccaa 360840 ggcagagaac ttggaaaata cagaaaagcc accaagcaaa ataatctccc aagaaatcat 360900 aatttcacca cacaaaagta accattgtca acattttggt gaaaatcctt aattaaagag 360960 actcttaaaa gatgccagtt cgctgccact tcttcctttc tccacaccat cctgcaccct 361020 gttttgaaat gcagaattgt ttctaaatca ttccaggaaa attattagtt ttctcaaata 361080 tctctggagg cgagtctgtt ggcagtcatt tctagtttct cacaaacctt gaagttagga 361140 aattatttgt gtagcttttg agcactgggc cagaagtgag ggatgtttgg gttctagttc 361200 cagctctacc acttatttac caactggccg acctcaggca agtccaggct agcggccccg 361260 cctcaagccc ctccagatgc agcatctgca accccacttc cttcacttcc tttcgcctca 361320 gtttcccaac aatttcctag taattgtact gaatcattgt ttttcatttt ttacattaaa 361380 atttatttat tttattttat ttttaaagac tttatttttt agaacagatt tagatttgca 361440 gcaaaactga gtggcaagta cagaaagttc ccatatattc cctgcccccg cacatacaca 361500 gtctccctca ctatcagcat ccccaaccag agaggtacat tggttacagc tgatgaatct 361560 acatcgacac gtcattatca cccaaagtgc atagtttgca ttggcgttgg gcattttagg 361620 gcttttgaca catgtatgca ctattgtaat atacagaata atttcactgc cctaaaaatc 361680 ctctgtgctc ctcctattca ttcctccctc caccccattc ctggcaacta ctgatctttt 361740 tactgtctcc acagttttgc cttctccaga atgtcatata cttggaatca taaggtttgt 361800 agccttttca gattggcttc tttcactcag tgatatgcat ttaaggttct tccatgtctt 361860 tttatggctt gatagctcat ttctttttat cattgaatac tactactcca ttgtctggat 361920 tatacacact ttatttatac attcacctac tgaaggatgt gttggttgca tccaagtttt 361980 ggcaattatg aatgaagttg ctgtaaacac ccatgtgcag gtaattgtgt tgatatgcat 362040 ttttaatgct tttggataaa cactcaggag cacaattgct ggattgtata gtatgtttag 362100 ttttgaagga aactgccaaa ccatcttccc aagtggctgt accattttcc atttccacca 362160 acaatgagtg agagttcctg ttgctccaca tcctcatcag catttggtgt tgtcaatgtt 362220 ctggattttg gccattctaa caggtgtatt gtggtatctc attttgtttt aattcgcatt 362280 ttttggataa tatcacatgg agcatctttt aataagctta tttgccatct gtgtgtcttc 362340 tgtggtgagg tgtctgttaa actctttggt ccattttttt aatcaggttg tttgcgttct 362400 tatcgttgag ttttaaaagc tctttgtata ttttggataa cagtcattta gcaggtatgt 362460 cttttgcaaa tattttctcc cagtctgtgg cttgtcttct cattctctgg agatcagtgg 362520 tttttacact ttcttctgct gaagccaagt attgtggaag aagccatggg gtcaccagag 362580 gataggtgca cagggtagtg agggaaagtt ggagtgaatg ggcttggtgc ccccaccccg 362640 caacatttct cttgctttaa tcagagaagt ttgacttcat ccagattgca tatgaggact 362700 ttacatgagg ttcacctttt tatttgtttt aaaaggggtt tttactctca aaatgtttta 362760 aagaccactg aactagatga tcatcttaag gcccttttaa gatttatgat tctggaattc 362820 tgtggctcta tttttccaat gtaatataac cttcctctcg ttaaggaaaa atgagataaa 362880 cctgttataa acactcatgt gacatttttt caatacagtt ttcatccacg tagtgctcac 362940 ttagaatgat agaaacaata cacctaaaga atatgcacca ttcacttgcc cactcatctc 363000 tcaaagagag gaactttcaa cactagttat ctttttaaaa ataatcagag agaattctca 363060 gccacttcaa ttctagccca ggaaaaagag ggaaaataca tttgaaggtt tctggctcat 363120 gtgatacatt tgcaaaccag aaccaagatg atatgactct catttattag tgactattgc 363180 aaagctttgc aggctattaa gcaggctgtt caatttaggg tgatatggac atgtgcatat 363240 tggccaatta tatatgctca gatcgtatgt catttttttt ctgcatttta gtctaagtgt 363300 cagataggtg tttcatgatg ttttataaac acttctgttc acattaacat tgttcattga 363360 tttggcaagg aatgaagggg tgtcattttc atgattttat ttgtatatta tgtattccac 363420 agaggatttg aaatgcctta ccaaatttta tgtaatgtaa aggggtaaac caatatttga 363480 cacatcatta taaattgagg ataatctgaa gaaaataata aatccaggag acagattatc 363540 acactgatat ggtttggctc tgtgtcccca cccaaatttc atcttgaatt ttactcacat 363600 aatttccatg tgttgtggga gggacccagt gggagatcat ttgaatcata ggagtggttt 363660 cctccatgct gttctcattg tagtgaataa gtctcatgag atctgatggt tttatcaggg 363720 gtttccactt ttatatcttc ctcatttttt ctcttgccac caccatgtaa gaagtgcctt 363780 tcgcctccca ccatgattct gaattctgaa ccctccccag ccatgtggaa ctgtaaatcc 363840 aattaaacct ctttttcttc ccagtcttgg gtatgtcttt atcagcagca cgaaaatgga 363900 ctaatacagt aaattggtac aaggagtggg gtgttgctga aaagatagcc gaaaatgtgg 363960 aagcaatctt ggaactggat atcagggaga ggttggagca gtttggaggg ctcaaaaaag 364020 acaggaaaat gtgggaaagt ttgaaacttc ctagagactt gttgaatggc cttgacaaga 364080 atactgatag tgatatgaac aataaagtcc aggctgaggt ggtctcagat ggggatgaag 364140 aaactgttgg gaagtggagc aaaggtgact cttgttatat cttagcaaag agactggtgg 364200 cattttaccc ctgctgtaga gatttgtgga atttgaactt gagagaaatg atttggggta 364260 cctggtaaaa gaaatttcta agcagcaaaa cattcaaaag gtgacttggg tgttgttaaa 364320 accattctgt tttaaaagag aaacagcata aaagttcaga aaatttgcag cctgatgatg 364380 cagtaggaaa gaaaaaccca tttttttgag gagaaattca agctggctgc agaaatttgc 364440 ataagtaaca aggagccaaa tgttaatccc caagacaatg gggaaaatgt ctccagagca 364500 tgtcataggt cttcatggca gcccctccca tcacagaccc ggaagcctag gaggaaaaaa 364560 acagttttgt gggccagtcc cagggtcccc atgctgtgtg cagcctagga acttggtgcc 364620 ctgcatctca gctgctccag ctattgctaa aaggggctga ggtaccacgg tttcagaggt 364680 tgcaagcccc aaaccttggc agctttcatg tggtgttgag cctgtgtgta cacagaagtt 364740 aagaattgag gtttgggaac ctccacttat atttcagaag atacgtggaa atgcctggat 364800 acccaggcaa acatttgctg cagaggtggg gccctcatgg agggcctctg ctagggcaat 364860 gaggaaggga aatgtggggt tggaaccccc acacagagtc cccactgggg cactgcctag 364920 tggagctgta agaggaggac cactgtcctc cagaccgcag aatagtagat ccactgacag 364980 cttgcaccat gtgcctggaa aagccacaga cactcaacgc cagcctgtga aagcagtcag 365040 ggttggaggt ggtggtggct ataccctata aagccacagg ggcagagctg cccaagacta 365100 tgggaaccta cctcttgcat cagcatgacc tggatgtgag acattcagtc aaaggagata 365160 ttttgaagct ttagaatttg actgccctgg tggattttag acttgtgtgg gccctgtaac 365220 ccctttgttt tggccaattt ctcccatttg gagctgctgt atttacccaa tgcctaaacc 365280 cgcattgtat ctaagaagta actagcttga ttttgatttt acaggctcat aggcaaaagg 365340 gacttgcctt gtctcagatg agactttgga ctgtggactt ttggttaatt ctgaaatgag 365400 ttaagacttt gggggactgt tgggaaggca tgattgcttt tgaaatgtga ggacatgaga 365460 tttggagagg ccaggggtgg aatgttatgg tttggctctg tgtccccacc caaatctcat 365520 cttgaattat actcccataa ttccaaagtg ttgtgagagg gacctggtgg gaaacaattt 365580 gaatcatgag gccagtttcc cctatactgt tcttgtggta gtgagtaagt ctcacgagat 365640 ctcatggttt tatcagggtt tccgcttttg catcttcctc attttctctt gctgctgcca 365700 tgtaagaagt gcctttcaca agcataagga agaagtatac ttgctggagc agcaggctgt 365760 ccttcttctg acgatatgga ctgcaagtgc ctatgtttac tttgaccaag acggcctttc 365820 ttttcacaga aagccagggt tcaccccttg aatttcataa gacctctctt tgcagtgggt 365880 tagatactct tttatatttt tatactctgt caggaaaaca tttttttttc catttaaaaa 365940 tcagtctttt ggttgcttcc aagatggctg aataggaaca gctctggtct gtagctccca 366000 gcgagatcga agcagaaggc aggtgatttc tgcatttcca actgaggcac ctggttcatc 366060 tcactgggac tggttggaca gtgggtgcag cccacggagg gtgagccgaa ctggggcagg 366120 gtgtcacctc acccacaaag tgcaaggggt caagggattt ccctttccta gccaagggaa 366180 gctgtgacag actgtagctg gagaaacagt acactcctga caaaatactg cacttttccc 366240 cacagtcttg acaactggaa gaccaggaga taccctccct tgcctggctc agtgggtcac 366300 acgcccatgg agacttgctc actgctagcg cagcagtctg agatcaacct gcaatgctgc 366360 tgcttgatgc ggggaggggc gtctgccatt gatgaagctt gagtagctca cagcgtaaac 366420 aaagcagcag ggaagcttga actgggcaga gcccacctca gctcagcaag gcctactgcc 366480 tctctagatt ccacctctgg gggcagcaca tagcagaaca aaaggcagca gacagcttcc 366540 gcagacttaa acatccctgt ctgacacctc tgaagagggc agtggttctc tcagcacagt 366600 gttcaagctc caagaaccaa gagaccgcca cctcaagcag gtccctgacc cccatgtagc 366660 ctgactggga gacacctccc agtaggggcc gacagacact tcaaacaggc aggtgccctc 366720 tgggacgaag cttccagagg aaggatcagg cagcaatatt tgttgttctg cagcctccgc 366780 tggtgatacc caggcaaaca gggtctgggg tggacctcca gcaaactcca acaggcctgc 366840 agctgagggg cctgacggtt agaaggaaaa ctaacaaaca gaaaggaata gcatcaacat 366900 caacaaaaag gacatccaca ccaaaacccc atctgtaggt catcaacatc aaagaccaaa 366960 ggtagataaa accacaaaga tggggagaaa ccagagcaga aaagtggaaa attccaaaaa 367020 ccagagcgcc tcttctgctc caaaggattg cagctcctca ccagcaaggg aacaaaacag 367080 gatggagaat gagtttgatg agttgacaga agtaggcttc agaaggtcgg taataacaaa 367140 cttctccaag ctaaaggaac atgttctaac ccatcgcaag gaggctaaaa accttgaaaa 367200 aaggttagat gaatggctaa ctagaataaa cagtgtagag aagaacttaa atgacctgat 367260 ggagctgaaa accacagcat gagaacttcg tgatgtatgc acaagcttcg atagctgatt 367320 tgatcaagtg gaagaaagga tatcagtgat tgaagatcaa attaatgaaa taaagtgaga 367380 agacaagatg agagaaaaga agagtgaaaa gaaacgaaca aagcctccaa gaaatatggg 367440 actatgtgaa acaaacaaat atatgtttca ttggtgtact gggaagtgat ggggagaatg 367500 gaaccaagtt agaaaacact cttcaggata ttatccagga caacttcccc aacctagcaa 367560 ggcaggccaa cattcaaatt caggaaatac agagaacact acaaagatac tcctcaagaa 367620 gagcaacccc aagacacata attttcagat ttaaaaagta tgaaatgaag gaaaaaatgt 367680 taagggcagc cagagagaaa agtcgggtta cccacaaagg gaagcccatc agactaatgg 367740 gatctctcag cagaaaccct acaagccaga agagagtggg ggccaatatt caacattctt 367800 aaaaattctt aaaaaaagaa gaattttcaa cccagaatct catatccagc caaactaagc 367860 ttcataagtg aaggagaaat aaaatccttt acagacaagc aaatgctgag agattttgtc 367920 accaccaggc ctgccttaga agagctcctg aaggaagcac taaacatgga aaggaacaaa 367980 cagtaccagc cactgcaaaa acattccaaa ttgtaaagac catcgacgct atgaagaaac 368040 tgcatcaatt aacgggcaaa ataaccagct aacatcagaa tgacaggatc aaattcaaac 368100 ataacaatat taaccttaaa tgtaaatggg ctaaatgctc caattaaaag acacagactg 368160 gcaaattgga taaagagtca agactgtgct gtattcagga gacccatctc acgtgcaaaa 368220 atgcacatag gctcaaaata aagggtcgaa ggaaaatcta ctgagcaaat ggaaagaaaa 368280 aaaaaagcag gggttgcaat cccagtctct gataaaacag aatttaaacc aacaaagatc 368340 aaaagagaca aagacagcca caacaagaag agctaactac cctaaatata tatgcaccca 368400 gtacaggagc acccagattc ataaagcaag tccttagaga cctacgaaga gacatagact 368460 cccacacaat aataatggga gactgggaga caccccacag tcaatattaa acagatcaac 368520 aagacagaag gttaacaagg atatccagga cttgaactca gctctagacc aagtggaccc 368580 aatagacatc tacagaactc tccaccccta atcaacagaa tatacattct tctcagcacc 368640 acattgcact tattttaaaa ttgaccacat aattggaagt aaaacactcc tcagcaaatg 368700 taaaagaaca gaagtcacaa caaactgtct ctcagaccac agtgcaatca aattagaact 368760 caggattaag aaactgactc aaatccacac agctacgtgg aaactgaaca acctgctcct 368820 gaatgactac tgggtaaata acaaaatgaa ggcagaaata aagatgttct ttgaaaccaa 368880 tgagaacaag gacacaatgt accagaattt ctgggacaca tttaaagcag tgtgtagagg 368940 gaaatttata gcactaaatg cccacgagag aaagcaggaa agatctaaaa tcgacaccct 369000 aacatcacaa ttgaaagaac tagagaagca agagcaaaca aattcaaaag caagcagaag 369060 gcaagaaata actgagatca gagcagaact gaaggagaca gagacacaaa aagccgttca 369120 aaaaatcaat gaatccagga gctggttttt tgaaaagatc aacaaaattg atagaccact 369180 agcaagacta ataaagaaga aaagagagaa gaatcgaata gatgcaataa aaaatgataa 369240 agggatatca ccaccgatcc cacagaaata caaactacca tcagagaata ctataaactc 369300 ctctacgcaa ataaactgga aaatctagaa gaaatggata aattcctgga cacatacacc 369360 ctcccaagac tcaaccagga agaagttgaa tctctgaaga caccaataac aggtactgaa 369420 ccaaggtttg gaccaaccaa aaatgtccag gaccagatgg attcacagtt gaattctacc 369480 agaggtacaa agaggagctg gtaccattcc ttcagaaact attccaatca atagaaaaag 369540 agggactcct ccctaactca ttttatgagg ccagcatcat cctggtacca aaacctggca 369600 gagacacaac aaaaaaagag aattttaggc taatatccct gatgaacatc gatgtgaaaa 369660 tcctcaataa aatactggca aaccaaatcc agcagcacat caaaaagcct atccaccaaa 369720 accaagtcag cttcattcct gggatgcaag actggttcaa catacgcaaa taaataaatg 369780 taatccatca cataaacaga accaatgaca aaaaccacat gattatctca atagatgcag 369840 aaaaggcctt tgacaaaatt caacagcctt tcttgctaaa aactctaaat aaattaggta 369900 ttgatggaac gtacctcaaa ataataagag ctatttatga caaacccaca gccaatatca 369960 tactgaatgg gcaaaacctg gaagcattcc ttttgaaaac cagcacaaga taagaatgcc 370020 ctctctcacc actcctattc aacatagtgt tggaagttct ggctagggca atcaggcaag 370080 agaaagaaat aaagggtatt cagttaggaa aagaggaagt caaattgtct ctgtttgcag 370140 atgacacgat tgtatattta gaaaacccca ttgtctcagc ccaaaatctc cttaagctga 370200 taagcaactt cagcaaagtc tcaggataca aaatcaatgt gcaaaaatca caggcattcc 370260 tgtacaccaa taatagacaa acagagagcc aaatcatgag tgaactccca ttcagaatta 370320 ctacaaagag aataaaatac ctaggaatcc aacttacaag ggatgtgaag gacctcttca 370380 aggagaacta caaaccactg ctcaacgaaa taaaagagga cacaaacaaa tggaagaaca 370440 ttccatgctc gtggatagga ataatcaata tcacgaaaat ggtcatactg cccaaggtaa 370500 tttatagatt cagtgctatc cccatcaagc taccattgac tttcttcaca gacttggaaa 370560 aaaactactt taaagctcac atggaaccaa aaaagagcct gcatagccaa gacaatccta 370620 agcaaaaaga acaaagctgg aggcatcacg ctacctgact tcaaaccata ctacaaggct 370680 acagtaacta aaacagcatg gtactggtac caaaatagat atatagacta atggaacaga 370740 acagaggcct cagaaatgac accacacatc tgcaaccatc tgatctttga caaacctgac 370800 aaaaacaaga aatggggaaa ggattcccta tttaataaat ggtgctagga aaactggcta 370860 gccatatgta gaaagctgaa actggatccc ttccttacac tgtatacaaa aattcgctca 370920 agaaggatta aagacttaaa tgtaagacct aacacctaga agaaaaccta cacaatacca 370980 ttcaggacat aggcatgggc aaagacttta tgactaaaac accaaaagca atggcatcaa 371040 aagccaaaat agacaaattg gatctaatta aactaaagag cttctgcaca gcaaaggaaa 371100 ctatcatcag agtgaacagg caacctacag agtgggagaa aatttttgca atccacccat 371160 ctgacaaagg gctaatatct ttgtagaatc tgcaaagaac ttaaacaaat ttacaagaaa 371220 aaaacaaacc catcaaaaaa gttggcaaag gatatgaaca cctttacact gttggtggga 371280 gtgtaaatta gttcaaccat tgtggaagac agtgtggtga ttcctcaagg atctagaact 371340 agaaatacca tttgacccag tgatctcatt agtgggtata tacccaaagg attataaatc 371400 atgctactat aaagacacat gcacacatat gtttattgca gcactattca caataccaaa 371460 gacttggaac caacccaaat gtccatcaac gatagactgg ataaagaaaa tgtggcacat 371520 atacaccatg gaatactatg cagccataaa aaaggatgag ttcctgtcct ttgcagggac 371580 gtggatgaag ctggaaacca tcattctaag caaactatca tgaggacata aaaccaaaca 371640 ctgcatattc tcactcatag gtgggagttg aacaatgaga acacatggac acagcacaag 371700 gaacatcaca caccggggcc tgtcaggggt tggggggctg ggggagggat agcattagga 371760 gaaataccta atgtaaatga tgagttgatg ggtgcagcaa accaacatgg cacatgtata 371820 cctatgtaac aaacctgcac gttgtgcacc tgtaccctag aacttaaagt ataataaaaa 371880 aaaaagaaag aaaagaaaag aaaaaaagaa gtggctttta cctcccacca cgattctaag 371940 gcctctcagc catgtggaac tgtaagtcca gttaaacctc tttttcttcc cagtctcgag 372000 tatgtcttta tcagcagcgt gaaaatgaac tcatacacac acacagaagt atatctttac 372060 agttcccagg atggactgca agtttggctc taaatttcct ttgcctggcc aaaacaaaaa 372120 gaacacattt tattataagg ttcacaggct tttaattgaa aaaaaaaaaa aaacagttat 372180 tcaacatgaa aactcttttt cagacaaagt tctacaaagt ctatttctca caagtaggac 372240 tttggcaagg attgtgcaac tgacaattca aagtcattta ttccgtggtg agaaaccgga 372300 gtacagatct ttaccagtta ggggatgatc catgtgtttt gataatcacc ttggtggtga 372360 tcagactaaa ggtctcctat gaaaaccatt aacttcacac tatagctgat aggatgcact 372420 gaagccctta ccgctgactg catggatgag agctaggcca gagcattggc aggcagagtt 372480 tataacatgg ggcaggaagc attgaaattc tattccacct cttggtgtat caggtcagga 372540 gtcaaatctc ctatcttcct cttctggatc gctttcctcc tgaagtgtct ggcatagatg 372600 tctaggtata gcttggcatg gtggtgtgtg cctatagacc cagctacttg agaggctgag 372660 gtgggaggat tgcttgagcg caggagtttg aggctgcagt gagccatgac cacaccactg 372720 tactccaccc tgggtgacag agcaagaccc tgtctctctt tctaaaaaaa caaaacaaaa 372780 caaaacaaaa caaaaagaaa aaaagatgtc caagtgtgtt ctggttactg ctgctgactg 372840 ctaaatttaa cagctagaaa aaaaaagttt ggactctatg gatcataaat ttggataaga 372900 cacagaggga atggcttgtc tcatgttcac aatgtctaaa gtcttaaatg gggagagtcg 372960 tcaaccaggg gtaatttgag agttatgggc tggaaccacc ttgaggcatc tttattcata 373020 ggctagcaat tgatgttggc tgttggctgg gacgtcagct ggagctgtca actgggagac 373080 ctgtctgata tcccagcata ggacactaga cctctcacaa agtggcgagg gctccagaag 373140 caagtgtccc agctgacaaa aaaaaaaagt ttcatagcct tctacgacat gcacttagaa 373200 gtggtaatgt gtcacttcca gccctttctg ttgattacaa gtgagtcatg agtccactca 373260 gtttcaaggg agagggccca gatcccatat ctccatggga agagtgccaa gaacaccttg 373320 tagaaaagct tgtggatagg agatattggt gtggtcatcc ttggaaaaca caatcttcca 373380 cagtgtgcaa gagaggcttc ctgctctgca ttgtggctta attattgttg aaataccagg 373440 caagaaaagg taggatccag ggaaacaaat gtatccagga tgttttggtc tgccttttct 373500 aggaaaaaag gaaaccctca aagcctctga gactaggtca ccccagtggg actagaagtt 373560 ccacgtggaa ccttctgcaa actcctctgc aatagatgga ctgtgcattt tccaaatgtg 373620 tctttacatc atctcctttc tgaccttggg aagatagtaa ctgactgtgg agtaggaaat 373680 ccagaaccct gattgtttta aaatatatta cagatacaag taatgaaaag aaggctccta 373740 aggaaaatat agatccgtaa tggctttgtc ccaaaagcta ttaggctata atattttatt 373800 acaaaggcta tatttattac aaaatgtatt taaataaata cttaatattt atttaaataa 373860 ataatattta ttttattatt aataattaat atttaaataa atataatatt tcttacaaaa 373920 attaaaaact gggactttat atttaaaggt gagacattaa attcttttta aaaagtgcac 373980 atgtaagatt tttttctcaa gtcaactgaa ccagttcatc agtttcacta tgaatgtgtt 374040 gatgcaccaa gtatttactt tctagaacat ctagtagacg tcactaaaaa attataccaa 374100 gttgaaaaat gtcactgaat cagaggcatg tggttggtta tgtagtcatc tgtgccagct 374160 gggaatatag caataccaaa tgaacagcac tgccatgttc ccttgctggg ttccagcaaa 374220 aacactcatc ttcactgtcg tctctctttg agacctctta gagaggactt tgatgagtgt 374280 atggtcttat acacactagt ctaacaatac acatttgctc aaggattggg ttacgagcag 374340 gctcttcacc tttcaggtga acaattacac atcaggagaa ggatggaagt ttcctatcta 374400 tgaacaaata tttcccaaag caataatctc tttattcaac tcacgtaatg agaagtcagt 374460 tcctctgtgc cataaagcaa tctctttgaa gtcttcagta atgttgaggg ttttaatgtt 374520 gagggcttta tcaaactaaa cattcaagtg tcttaggctt tccccttagt tctttgagca 374580 aattggttgc tatgaagtat gttagtgttc cgaatgaatg gatagcatga tgggggatgt 374640 ctaggtggtt ccagaattta gattgtggtt tccataacaa agtgtggcag tattggcatt 374700 agggaagaga aatgacttct aaataacttc tcaaagttta ctaaagcctt aagaatgtag 374760 gaaatggcca caaaaggagg tatacaaaac attcctctgt ctttattcct ctttatacaa 374820 acgtattcac tttcccatca gcaagtcata aaatacttct catcttgcat tacagtagga 374880 cacctactat aacaataggc tacaaaatgt ataatggctc aaacacctag cagtttattt 374940 cttatttact taacaatgct gggtccacga acatgttgat atcataaccc tcttttatgt 375000 ggtcactcag ggactcaggc tgttgagggc tctgtcatca tgaatgggtg gcttccaagg 375060 tcatcctaag agttatctcc attctaacca gtccagccag aaaggcagaa caggcttgga 375120 ggagcaaaga tatccatgga tagatcatcc tcttaaagtc attgtagcat tgtgataggg 375180 ctcttttcac aaaacaagga tacaatccat gttttcaaga ttttacattt tagtagccac 375240 aatacaaaga agctaagata gtcttgtgat ttgtcatcat ggctgttaat ggagagtgtt 375300 ttaaaagcac tgatatcagg gctccaccct cagcttccaa tcatcaggtt tggatggaac 375360 ctgacagctg catcttgtaa aactccacgg gagattctga gagacagcca agtttgagat 375420 tcacaaacct taagagaaaa aatctccttg aattgccata acaaactacc agtctaataa 375480 aacatacata ttcctttgac tactcttaaa tgaaacaaat aggtaataat ttacctgtac 375540 atataattaa aaatgtaatg tattttataa ccatcatata aaggagaaat tatattaaac 375600 tatattaaaa taaaatgata tatatttcaa tgcagatgcc caagcttgac taaagtagga 375660 aacataataa agtaataaaa tgcttatatg tacttataat gaatgtttgg ctatgagaag 375720 atgatcagag gctttttgtc caagaagtac aggcatatga aaaagtagag caagagatgg 375780 acaccagact gagaaaacta aaaactaacc aacctatttg tgtatgataa aaggagagaa 375840 aaaaaattga ttagtaaaaa tatgctaccg tgtggtctga atgtttgtcc cttccaaaac 375900 tcatgttgaa atttaatccc ccatgtggca gtattgagaa gtgggacctt taagaggtga 375960 ttggttcaag aagattctgc gctcatgagt ggttgaaacc attcacggaa taacgggtta 376020 atggatcaat gagttatccc aggagtggga ctggtagctt tataagagaa ggaagagaga 376080 cctgcgctag cacactcagc ctccttgcca tgtgagccat ctcgggaccc cgcagagtcc 376140 ccagcagaaa gaaggccctc acccaatgtg tccccttgac ctaggatttc tcaacctcca 376200 taactgtagg aaatgaattc cttttctttg taaattatcc agtttcaggt attctgttat 376260 aaacaacaga aaatgggcta aaacacacgc caagaaaatt gaaagactgt ggaagtgaaa 376320 gaagaataaa aaatgaagta attttgcaaa tgagtctggc tttattataa gtgtattgtc 376380 aaagtgattc cctttgttat aagatgaaaa agagccaaaa tggatagaaa catttatcct 376440 atcttaatat cccactacat tcaaggcaaa tattcagtca gtctctagaa cttaacaagg 376500 ccttggagat gatatccttt ggatgagcaa tggagaagac aagatggatt ggaaaaagaa 376560 acaaacaaac aaaaaaacat gtaagaggct atcaggaaaa ctctggagac gatgtcaatg 376620 taaaacagat acaaacctca aaataatttt aatatgtaca ttgcacaaaa atggacttct 376680 tatcatgtta caaatttatt ttaaaacata taggaggcaa caacaatatt tcattgatgt 376740 gtactatttt ataattgttg gctctaattt tatttagtag agtcttacat ctcctctcta 376800 catatttaca tccggttgta ttgtttttgt agtacctgtt caactgcact gaaatcattt 376860 caattaaatg catggttgaa aagctgacat aatacattca attgccaaat tgcataaagt 376920 gaataagcta tttaataatt tggagaaaat atattccatt taaacttcct tctctataac 376980 cagttcatac actggacctt ttgggcacag ccatgtgaaa gcttttcaaa acttttcact 377040 actttttttt gagacggagt ctcactctgt cacccaggct agagtgcagt ggtgcgatct 377100 cggctcactg caacctccac ctcccaggtc caagtgattc tcctgcctca gcctcccgag 377160 tagctgggat tacaggcacc tgacaccaca cctgactaat ttttgtaatt ttagtagaga 377220 caggatttca ccatgttggc caggatggtc ttgaactcct catctcaagt gttccgcctg 377280 ccttggcctc ccaaagtggt gggttacagg catgagtcat tgcacccagc cactatagat 377340 ttttatttgt agtagattta gttcagtagg gcatttgaga ggcataggaa ctggaacaaa 377400 tccttcattg tttgggactg ccttgcacat tgtaggacat ccagtacagt cccttccacg 377460 aagtggcagc agcagcctcg ggctgtccaa acaccctgtt agggacagtg ccactcccgg 377520 aaccacagaa gaaccacaat cataggagaa gcatacaaca aacatggtgt tcatcggacg 377580 gtcagcttca gtggcacttt tgagcaagca cactatttgg ttgtagaatg agtccctggc 377640 agggcacccg aaaggctgat gtgtgactca tccctagtac ctctgagaat gctgaaatct 377700 cctccttctc caagctgagt ggcagctttc tggtccagac tacttaaatt gtgacttgag 377760 gaattttctt cactttttcc tttgagtcat tctgtttttg atcaagatgc gatagaatga 377820 aggattcttt cagggtctgc tgtcacatcc ttcctttggg aacagataga aaatctggcc 377880 tggcttgaag agtttgtcct caaacatctg gtaagccata ggcatcagca tctcttactt 377940 ctccagagac atttagatgt gtcccccatc tccatggagg cccatggcaa ggggacccct 378000 agttgtacta gagcttcctt ctgggcacag ccacactgca caggcactgc agtgtacagc 378060 acagctcctc cagcttccgg aagactccat tatctagaaa agtgctgaga aatggagaag 378120 ggggttcctc tggggtggag atggaaagag gaaaaggaag ggagaatgtc caagcaaaat 378180 gagagaaggt gagggacagc agaattgaga gtgagggaga gggagagagc aagagactgg 378240 gttgagatgt cttgtacatg ggggtgtcct cgtggcttca ctcccctttc gtttgtacca 378300 ctccgtttcc ccagactctt cctaaatatc cccttattgg ctacaagatc cagattgcct 378360 agaagctcag atttgctgac agcacctcaa gactggttaa tgacatatag attttttctt 378420 gtttccatct ttgggatttg gagcaatctc cagagttgca aaagcctacc ttgttgcaat 378480 aatatttttg agggtccaca ctgtctgctc acttgctcta tgctgctggg cacagtggtg 378540 tggccatcca gggtgggaga gaccacctgg gatatggaaa ttaccagcag ccctgttttg 378600 ctcttgcagt ggttgccaaa gcacacgaag cattctggga atctgaattt ctgttgtttc 378660 tcccaaatgg cccctgaagg gcaacaggca gcacacatgg accacatttt gccagaaaag 378720 tccagaaaga agatggctgc tgttgtcaac tattggcatt tcaacaggac ctatttttat 378780 ttctcagtat atttgcacaa ctaggaagca tctgctgaca aggatgagat gataagctgt 378840 attgatgcca aaacaggact agaaaaacag gcttgttctg caaatggcct gcatcctgag 378900 agtccgtgtt aagaacattc tctctctgca ggcaatatct gctcttaaaa cattaacact 378960 tgaaaggaag taaggcttgg aatccttagc atagttatgc acacactagg ttctcagtaa 379020 gtgcatgctg gatgaaggaa cccacacgca ccttaaggag gatggaacat tggcagccca 379080 agaaaaaagt cactccccag aggccgagtg ccatgtcttt gacctccatt ggcaaggtca 379140 tggtgaaatg ctgtctcttg gggtcgctga ggtcccagca cggtgtgcct tcacaccgtg 379200 caaacaataa gaagagaaga gaggcacaca tgtcaccttt ccaggcaggg acatccaagc 379260 tgtttgagtc tccattctgt gatttccttg aacaagaaag ggattattgg tgaatgaggc 379320 cagcatcctg ggtgggaaca aaaaaggaaa ttggtagaaa gtacatcatc caagttggtc 379380 taactcagcc ctgtggcttg ggcgggttcc taggatatcc agccggaggc agaggctcta 379440 ggggatgtga ggctgcactg ggtatgatga cacagaggac tgtgagaggc agagaaaagg 379500 ggagaagagc tgaggccctc ctagccctaa cctcccagct cacaccctct gctatctgcc 379560 acctccaggc caacaccacg gccatgggag gtttgcccat ttttctgata gacacattct 379620 ttctctacca acagcccaca tggaacataa gtgaagtaat tcagcagttt ccttcttaat 379680 ctgctgtctc tctgctgctt actcattctg tgctgtttgc tttagatcaa ggtgccccag 379740 ggtaccaaaa gctacattat cctattcaac tgcatggaaa ccaagatccc gaccattctg 379800 gtttgttgtt attgttacgt tagttttaaa ccttagccat tttccattct gggcagttac 379860 aactctgttt actatgagtt cctctgtgta gatgtttctc ccatacccga cctacaaact 379920 gctacgtgag cagtaacttg tcaccatgtt atccgcataa agtcagggat tgataaactt 379980 gggagccttt agctcttgaa ggtgctgatg aggaagggga gaggggagga gaaggaattt 380040 gtttgtgaga tggtcagtgg gctgaatagt ggtatgacca aaaagtgtta ctataaatac 380100 acataatctg gaaaacaaaa atactgtcat ctcctccctg caaggcgctg tgattaggca 380160 ggatggagct tattgctgca gtgttagaaa atgcatcctt gtagtcccaa aaaagcctgt 380220 tccatcctgc ccatctcttg ttctcaatac ttcttacttc acggtcactc attttcttcc 380280 tgtccttggg ttgaggtctc aacttcttgt aatagaattt tttcagttat aagcgacaga 380340 aatccaactc acactatctt aagcaaaaag gggattcact gatacgtgtg ttaggaagga 380400 tatatgaaag ctcaaaggtc aagtgaaaaa aatgtaagaa cgaagacctt ggtggggtgt 380460 ggtggctcac gcctatcatc ccagcatttt gggaggccga ggcaggtggg tcacaaggtc 380520 aggagttcaa gaccagcctg cccaagatgg cgaaacccca tctctactaa aaacacaaaa 380580 attagccggg tgtggtggca ggctcgtgta ttcccagcta cttgggaggc tgaggcagag 380640 aactgtttaa acctgggagg cagaggttgc agtgagttga gatgtgccac tgcactccag 380700 cctgggcggc agagtgagac tctgtctcaa aaaaaaaaca aaaaaaaaaa actaagacct 380760 tgtgactact acctactacc tggatctctc tctctctctc tctctctttc tctctctctc 380820 tctcaccccc ccacactatc acctctcctt gttgtcagta gtttcctttc tgcagacagg 380880 agttccatgt gctgggaaga gggccattca gagcctcgta ttctcatcct ctcagtttag 380940 caatgcgaga agaaaaaact tttgtctcac aacctcatat acaatctcag aaataggctc 381000 ttattttctg gcttgaggct gtccagaggc accaggcact gtgatggtct cactttctgt 381060 cctggatcta tctgtggggc ccagacagca ggatctattt cagaaaatag gcgagagagg 381120 aaaaacttat gtggccgtaa aaaacagcgg ttttcaagtg gcctatcccc atccacatca 381180 taaacttttc tgctgaggct taaaagtgct tagacttcaa acttgatcta aaacagaaat 381240 cctacctgga aaaatcacct tccagtcact tagccaatcg ctcatcactc tctgtctctg 381300 aatctcacca cgagtttcac acgtctcccg agagagcgtc tcctttatca ttaccacatg 381360 tggagtcagc agattgggtt tcatctaagc tctgcctacc tactatccga gttccctagc 381420 aggttagtga ctttctctgc ctttttgttt cttgatgtga aaaggaacaa cagtggctgc 381480 tcacagggtt gtcagttaca tggtcaatta cattacatgg acaattcatg atggtgtcag 381540 acctgtctga gaaaaggtgg cccatgttac catgacaggc cccaaggcta acagcccctt 381600 tctgggtcat ggctcataca aaggagccct ccttggtttg ctggtgctct gagacttgca 381660 aatgcattag gaattttaca ctgtaacccg gttttaaatg ggtccagagc atccccattg 381720 ctagactact gtgctgagga agggcactgg ctcattgtta catcccatga acactctggg 381780 tctcctagac ctcatcctct ttgagcttct ctctctcact ctctctctgc gcattcagga 381840 gtgtacacat ttctgtccag caccctgaag tctctggaag agaaggacca tatccaccga 381900 gtcctggaca agatcacaga cactttgatc cacctgatgg ccaaggcagg cctgaccctg 381960 cagcagcagc accagcggct ggcccagctc ctcctcatcc tctcccacat caggcacatg 382020 aggtgaggca tctgtgggct tcctacagga gagacataaa gaaaacatgc ccccaaacct 382080 atgtgacagc tggccgggaa ggactggtgc ctgcatatgg agagtgcact tgtgacagtt 382140 cctggcatag aataagcata aatgctatag gaggacagaa gagagaggtt ttaaatctgc 382200 gagggtcaca gggcaagtgt cagagaaggc atagaggaag cgatacttac gcttggttta 382260 aagcatgtgc tttggggcag tggtttagag attgggtgca gtgtgcaaat aggaggaggg 382320 ggccaatcaa gagaagtcag tgaatgtaca catcccctga agacactggg tacatctgtt 382380 atggtccctg tgtacactcg gatattctaa atgagagacc ctggggccag atgcctcacg 382440 gagagtcaat gttgactcct tcatacctgt tgaacccctt cttgtcaccc ccattgccat 382500 taccctagtc taagccacca tcattttctg ttggacttct gtgccagtca ctggatgtgt 382560 atccctgcct gtaatctaga tcctttctag atcattctcc atgatgtgtc cagagtgatc 382620 attctagaac caaatctgat gtcatcctcc tgcttaaaac ccttaagttc tcattgcttt 382680 tagataaaat ataaaccctt tcactttgtt tttattactc cttatgattc agcccttact 382740 tagcttacaa ggacttcctc atgtctgagc tctagccata atagctgact gttggatgag 382800 tcatcggggg gaggttcttc ttcaggctgc agattggcgg tcagccctcc tgacctcagc 382860 tgggctcact cacacatctg ggaggcagct gcctgaggcc agggtgactc tgctctatgc 382920 ctcatgtctc ctatcctcct tgtacccaca tgttagctgg gacatgttct catcgcaatg 382980 gcagaggcat gagaaagtga tcctgtttgg gcaagtgcat tttactcttt tctttcactc 383040 atgtccactg acatttcatt ggccaagcaa gcatgtgggg tgtccagagt caaagaggga 383100 catgttgccg gggtcatgac tatttctgag caataatcta acctatcata gctcagatct 383160 cactccttgc aggaagcatc tcctaatcct taagacctag ttggaactta cactctgttc 383220 ttccctatgg ttactgccca ttttactatt tttctgccca tttagactga caactctgtg 383280 agccatcatt gcaatatggc ttgcttaccc aatatcacct agcatgatgt agagcacata 383340 gtaaatactc aacaaatgtt ttctgtaaga gctaaggaag gacatcagca gacaaaatag 383400 agtctttcta tgccaaaagg tgaaagtggt ctcatttcca ttccattgtc ctgtaatttg 383460 gctagccaaa agcttagtgg ataccattcc cataagtaga cctcatctgc agggaagaga 383520 tggggagact gctgggttat ttattgcaga ctccagcagg accacaacaa tgattcaaag 383580 tgatgacact agaaggacag gtgccaatgg gtgatgaagc cacaatgacg atgtcaagtg 383640 gtatcactaa aaggacaggt actcatgggt gatgaagcct acatgacctt gggcttacac 383700 caggacccta ggaatgaaag agattccttc tcttagtggc tatgagggaa ggcctatgat 383760 gtcttaagga ggttggattc gatcattttt aagggacctt caaatcctta gaccgtgatt 383820 caaatggtaa gaagtttgct ccattaaact cccaggcacc accctttccg gagacaacct 383880 ttaaaaatta ttagctcctg ggaaaataga tgtatctcat tttctttgta tccctcacag 383940 tgccatatgt gaagacttac atatggtata tgcccccaac attactactg agtgagtgaa 384000 caaagaaatg agggaatgaa tggatgaaca aatggctcat ggcaggcttt tccctgccct 384060 gtgaattcgg cttctacttg gtaagaaggt gattgcaatc tctgttctca gggttcccca 384120 aggattcctg tgtaacagat gaaggaatca cgtctgtcag gtagagtagg tgactgcatt 384180 cagagtatac atttccagtc tcccctgtct ttttcttttg atgagtatta tagagaggga 384240 agccatgagt ggattagatg ccaaaatccc tggctgagag aataacctta ccctggagga 384300 aaacatatta gctttgactc tgagctggga atttcggtga tgttgtagat tcaatgcatt 384360 gcagttgggt gtttttattt gttgaaagga attgctgaat tttcaaatcc attaactgct 384420 tgtcagcatt agcaagccta attagttaat actaagtaaa tttgcactaa atatacaacc 384480 ctggctgatt ttactggcca cgtctggcag agggcagcag cagggagaaa gctctgtaga 384540 gtttctgttg gaatcgtgtg aaaagctgga gaggttgctt ctctttctct ctctctctct 384600 ttctctctct ctctctgaca cacacacaca catacacaca cacacaattg taataataat 384660 aatattttgg ttcctcacta agccaatcta aatcgcagaa gtctattttg ttaagtaagc 384720 ttggccccag ccatatgttg ctactcagag aatttaatat cagatttcat ctgactgtaa 384780 acgtgaatca tcaggttgca caaggaacac agtggcagat ccagggggca tttaactttt 384840 atagcatttt aaatgaaaaa aaaaaaaagt aacacttaaa caagtaattt agatcatgct 384900 gtaggccctg aatagctttg atgttgtgtt ttcatggcaa gtctccaact tgagctgaat 384960 tttcccctac taaaaatgca aatttttcta agaccttctc ttggtcctgc tactcatgat 385020 acatatttct tttaaaagaa atttcaaact agataatagt tgttctcctc cccacccccg 385080 ccaccagtag tgtggtgggg cagcagagtt gtggctagtg gaggagagca gaggaggaga 385140 gtagggaaag gagaatgcca tttgcctaca tttccctctg cccatttccc gctgcccatt 385200 tccccccttg ttttcctgaa cgtgaactga gctctgggca ctgttttagg cctagcaggg 385260 gacaggataa agcctgcttc tctaggaatt cgcactgagg gtgtgagtgt gtgcacgtgt 385320 gtgtttggag gcgggagaat aaacacaaat aaataaaaag gagaatttca ggcagtgata 385380 agagtgctga gaaaaacaga acggtgtgaa agaggaaggc tgagcctgca gaggcttgag 385440 gctgctgcca ctgggtagcg gtaggccttt ccgaggaggc ggcatttgaa gaccggagga 385500 aggttcatcc cagcaagtag gaacagcaag tgtaggtccc ctaagtcttg ggggagctta 385560 gttcctttaa gggcagcaca aaaatcagtg tggctccgga gagcacatta ggggagagag 385620 gcaggaagag cttggagaca tggatggaag ctggaccagt tgggccttgt tgaacatgga 385680 aaggcattta gatcgtattc tgagttaaat gggaagtgac gtgagagatt taacaatgga 385740 gcgtcttgaa ctgctttact catttaaaat acccactcct gcttggctga atatctcatg 385800 ttgtcttttt agaagctttg gcgatcctat ttgaatgcat ttaggtccta ttggagggga 385860 ataggatctc atttgaggcc acggaggtcc atggaagtca cctgcatagc aaataccctg 385920 aaagtggctg cagggagagt gtgagggtgg gaccgccctg gtaggaggtg gaaaatgaaa 385980 aacacacggc catgagttcc agattagggc ttctgaaagc cctcagcttt cccagctccc 386040 atcctaaagt gggtctttaa acaggaagaa agaaagattg ctaagtgtct ttggagttcc 386100 tcttccttcc ccttctaggg atttcagcac tcctggggct cgggttggct ctaaagtagt 386160 cctttctgtg tcttcccacc tacagtaaca aaggcatgga gcatctgtac agcatgaagt 386220 gcaagaacgt ggtgcccctc tatgacctgc tgctggagat gctggacgcc caccgcctac 386280 atgcgcccac tagccgtgga ggggcatccg tggaggagac ggaccaaagc cacttggcca 386340 ctgcgggctc tacttcatcg cattccttgc aaaagtatta catcacgggg gaggcagagg 386400 gtttccctgc cacggtctga gagctccctg gctcccacac ggttcagata atccctgctg 386460 cattttaccc tcatcatgca ccactttagc caaattctgt ctcctgcata cactccggca 386520 tgcatccaac accaatggct ttctagatga gtggccattc atttgcttgc tcagttctta 386580 gtggcacatc ttctgtcttc tgttgggaac agccaaaggg attccaaggc taaatctttg 386640 taacagctct ctttccccct tgctatgtta ctaagcgtga ggattcccgt agctcttcac 386700 agctgaactc agtctatggg ttggggctca gataactctg tgcatttaag ctacttgtag 386760 agacccaggc ctggagagta gacattttgc ctctgataag cactttttaa atggctctaa 386820 gaataagcca cagcaaagaa tttaaagtgg ctcctttaat tggtgacttg gagaaagcta 386880 ggtcaagggt ttattatagc accctcttgt attcctatgg caatgcatcc ttttatgaaa 386940 gtggtacacc ttaaagcttt tatatgactg tagcagagta tctggtgatt gtcaattcat 387000 tccccctata ggaatacaag gggcacacag ggaaggcaga tcccctagtt ggcaagacta 387060 ttttaacttg atacactgca gattcagatg tgctgaaagc tctgcctctg gctttccggt 387120 catgggttcc agttaattca tgcctcccat ggacctatgg agagcagcaa gttgatctta 387180 gttaagtctc cctatatgag ggataagttc ctgatttttg tttttatttt tgtgttacaa 387240 aagaaagccc tccctccctg aacttgcagt aaggtcagct tcaggacctg ttccagtggg 387300 cactgtactt ggatcttccc ggcgtgtgtg tgccttacac aggggtgaac tgttcactgt 387360 ggtgatgcat gatgagggta aatggtagtt gaaaggagca ggggccctgg tgttgcattt 387420 agccctgggg catggagctg aacagtactt gtgcaggatt gttgtggcta ctagagaaca 387480 agagggaaag tagggcagaa actggataca gttctgaggc acagccagac ttgctcaggg 387540 tggccctgcc acaggctgca gctacctagg aacattcctt gcagaccccg cattgccctt 387600 tgggggtgcc ctgggatccc tggggtagtc cagctcttct tcatttccca gcgtggccct 387660 ggttggaaga agcagctgtc acagctgctg tagacagctg tgttcctaca attggcccag 387720 caccctgggg cacgggagaa gggtggggac cgttgctgtc actactcagg ctgactgggg 387780 cctggtcaga ttacgtatgc ccttggtggt ttagagataa tccaaaatca gggtttggtt 387840 tggggaagaa aatcctcccc cttcctcccc cgccccgttc cctaccgcct ccactcctgc 387900 cagctcattt ccttcaattt cctttgacct ataggctaaa aaagaaaggc tcattccagc 387960 cacagggcag ccttccctgg gcctttgctt ctctagcaca attatgggtt acttcctttt 388020 tcttaacaaa aaagaatgtt tgatttcctc tgggtgacct tattgtctgt aattgaaacc 388080 ctattgagag gtgatgtctg tgttagccaa tgacccaggt gagctgctcg ggcttctctt 388140 ggtatgtctt gtttggaaaa gtggatttca ttcatttctg attgtccagt taagtgatca 388200 ccaaaggact gagaatctgg gagggcaaaa aaaaaaaaaa agtttttatg tgcacttaaa 388260 tttggggaca attttatgta tctgtgttaa ggatatgttt aagaacataa ttcttttgtt 388320 gctgtttgtt taagaagcac cttagtttgt ttaagaagca ccttatatag tataatatat 388380 atttttttga aattacattg cttgtttatc agacaattga atgtagtaat tctgttctgg 388440 atttaatttg actgggttaa catgcaaaaa ccaaggaaaa atatttagtt tttttttttt 388500 tttttgtata cttttcaagc taccttgtca tgtatacagt catttatgcc taaagcctgg 388560 tgattattca tttaaatgaa gatcacattt catatcaact tttgtatcca cagtagacaa 388620 aatagcacta atccagatgc ctattgttgg atactgaatg acagacaatc ttatgtagca 388680 aagattatgc ctgaaaagga aaattattca gggcagctaa ttttgctttt accaaaatat 388740 cagtagtaat atttttggac agtagctaat gggtcagtgg gttcttttta atgtttatac 388800 ttagattttc ttttaaaaaa attaaaataa aacaaaaaaa aatttctagg actagacgat 388860 gtaataccag ctaaagccaa acaattatac agtggaaggt tttacattat tcatccaatg 388920 tgtttctatt catgttaaga tactactaca tttgaagtgg gcagagaaca tcagatgatt 388980 gaaatgttcg cccaggggtc tccagcaact ttggaaatct ctttgtattt ttacttgaag 389040 tgccactaat ggacagcaga tattttctgg ctgatgttgg tattgggtgt aggaacatga 389100 tttaaaaaaa aactcttgcc tctgctttcc cccactctga ggcaagttaa aatgtaaaag 389160 atgtgattta tctggggggc tcaggtatgg tggggaagtg gattcaggaa tctggggaat 389220 ggcaaatata ttaagaagag tattgaaagt atttggagga aaatggttaa ttctgggtgt 389280 gcaccagggt tcagtagagt ccacttctgc cctggagacc acaaatcaac tagctccatt 389340 tacagccatt tctaaaatgg cagcttcagt tctagagaag aaagaacaac atcagcagta 389400 aagtccatgg aatagctagt ggtctgtgtt tcttttcgcc attgcctagc ttgccgtaat 389460 gattctataa tgccatcatg cagcaattat gagaggctag gtcatccaaa gagaagaccc 389520 tatcaatgta ggttgcaaaa tctaacccct aaggaagtgc agtctttgat ttgatttccc 389580 tagtaacctt gcagatatgt ttaaccaagc catagcccat gccttttgag ggctgaacaa 389640 ataagggact tactgataat ttacttttga tcacattaag gtgttctcac cttgaaatct 389700 tatacactga aatggccatt gatttaggcc actggcttag agtactcctt cccctgcatg 389760 acactgatta caaatacttt cctattcata ctttccaatt atgagatgga ctgtgggtac 389820 tgggagtgat cactaacacc atagtaatgt ctaatattca caggcagatc tgcttgggga 389880 agctagttat gtgaaaggca aatagagtca tacagtagct caaaaggcaa ccataattct 389940 ctttggtgca ggtcttggga gcgtgatcta gattacactg caccattccc aagttaatcc 390000 cctgaaaact tactctcaac tggagcaaat gaactttggt cccaaatatc catcttttca 390060 gtagcgttaa ttatgctctg tttccaactg catttccttt ccaattgaat taaagtgtgg 390120 cctcgttttt agtcatttaa aattgttttc taagtaattg ctgcctctat tatggcactt 390180 caattttgca ctgtcttttg agattcaaga aaaatttcta ttcttttttt tgcatccaat 390240 tgtgcctgaa cttttaaaat atgtaaatgc tgccatgttc caaacccatc gtcagtgtgt 390300 gtgtttagag ctgtgcaccc tagaaacaac atattgtccc atgagcaggt gcctgagaca 390360 cagacccctt tgcattcaca gagaggtcat tggttataga gacttgaatt aataagtgac 390420 attatgccag tttctgttct ctcacaggtg ataaacaatg ctttttgtgc actacatact 390480 cttcagtgta gagctcttgt tttatgggaa aaggctcaaa tgccaaattg tgtttgatgg 390540 attaatatgc ccttttgccg atgcatacta ttactgatgt gactcggttt tgtcgcagct 390600 ttgctttgtt taatgaaaca cacttgtaaa cctcttttgc actttgaaaa agaatccagc 390660 gggatgctcg agcacctgta aacaattttc tcaacctatt tgatgttcaa ataaagaatt 390720 aaactaaaga caacgagttt gttttttgta agctccactt cttgctagca gttcaccact 390780 gatcctctaa aatcaaagtg gttaaacgat ctgtcacaca cagtgagtct gaatgctaaa 390840 gcctctcctc acctcactcc ctctgcccaa cacccccagg tgtatcagga agtgtgtgga 390900 cactgtggtc aggcagaact ggcctcaatt cttggcttca ccacttacaa attttatgat 390960 cattggcagt tgatttttca gagtttcggc ttccttatca acaatatgat gataagtaat 391020 aacacctaat tcacacgatg gtggtgagga ctaactgagg tgctcattaa acatagttgc 391080 tgttttttaa tgcctggccc aaatccttcc ctgtgaggga gaagaaggat gcttgagagt 391140 ggttatttat gaatgaatga gtgaatggaa gaatgagtga tctgaaatga tataattagc 391200 ttaaaaacct ctccctcatt ctgaaggtaa agcaggaaca attggtccac ccccacccca 391260 ggtttccatt tcaggactcc cttccctttt tggagctacc tgcgtgcttc ctttacccat 391320 tttctcagat ttaactgatg aattgggagg gggtgggtat aggacttact gagatgcaac 391380 ataatattca cacaggctct gcagctagat tactgtttga atcttcattc tacctttttt 391440 tttttttttt tttttgcatc accttgggca agttgagttc cctgggcctc agtttcttga 391500 cttgtaaaga gagatgacag tgcatctgcc tggaagggtt cttttatgaa gaccacatgg 391560 ttcgctcatg gagagtatgg aaggaccgtg gctgacactg cttctccctc tccagagtct 391620 tccgaaactg cacgttggac tcatttcttt attaggatgg gttgagggtc ttctcattgt 391680 ttgagtcaca tggatttcag gaaactaatt cattttcttg tccaagcatt cccttggcaa 391740 gttcttcaat ccctgttttc aatggtttcc tcatttctaa aatagaaaca agaatagcac 391800 ttaccctata gcagtactgt gaagattaca agactggaca tgtgaagtgc ccaggatagt 391860 accacacata gtcagcactc aatccacatt agctattttt atcacaatta ttgttgccct 391920 gtctgagcat ctacatttaa tagaatgatg gatatgttta gatttacatt tttcacgtta 391980 ttatcgtttt gtacatgcct 392000 12 1366 DNA Homo sapiens CDS (233)...(691) 12 aggagctggc ggagggcgtt cgtcctggga gctgcacttg ctccgtcggg tcgccggctt 60 caccggaccg caggctcccg gggcagggcc ggggccagag ctcgcgtgtc ggcgggacat 120 gcgctgcgtc gcctctaacc tcgggctgtg ctctttttcc aggtggcccg ccggtttctg 180 agccttctgc cctgcgggga cacggtctgc accctgcccg cggccacgga ccatgaccat 240 gaccctccac accaaagcat ctgggatggc cctactgcat cagatccaag ggaacgagct 300 ggagcccctg aaccgtccgc agctcaagat ccccctggag cggcccctgg gcgaggtgta 360 cctggacagc agcaagcccg ccgtgtacaa ctaccccgag ggcgccgcct acgagttcaa 420 cgccgcggcc gccgccaacg cgcaggtcta cggtcagacc ggcctcccct acggccccgg 480 gtctgaggct gcggcgttcg gctccaacgg cctggggggt ttccccccac tcaacagcgt 540 gtctccgagc ccgctgatgc tactgcaccc gccgccgcag ctgtcgcctt tcctgcagcc 600 ccacggccag caggtgccct actacctgga gaacgagccc agcggctaca cggtgcgcga 660 ggccggcccg ccggcattct acaggacata acgactatat gtgtccagcc accaaccagt 720 gcaccattga taaaaacagg aggaagagct gccaggcctg ccggctccgc aaatgctacg 780 aagtgggaat gatgaaaggt ggaaccaggg aaaatgtgta gagggcatgg tggagatctt 840 cgacatgctg ctggctacat catctcggtt ccgcatgatg aatctgcagg gagaggagtt 900 tgtgtgcctc aaatctatta ttttgcttaa ttctggagtg tacacatttc tgtccagcac 960 cctgaagtct ctggaagaga aggaccatat ccaccgagtc ctggacaaga tcacagacac 1020 tttgatccac ctgatggcca aggcaggcct gaccctgcag cagcagcacc agcggctggc 1080 ccagctcctc ctcatcctct cccacatcag gcacatgagt aacaaaggca tggagcatct 1140 gtacagcatg aagtgcaaga acgtggtgcc cctctatgac ctgctgctgg agatgctgga 1200 cgcccaccgc ctacatgcgc ccactagccg tggaggggca tccgtggagg agacggacca 1260 aagccacttg gccactgcgg gctctacttc atcgcattcc ttgcaaaagt attacatcac 1320 gggggaggca gagggtttcc ctgccacagt ctgagagctc cctggc 1366 13 1128 DNA Homo sapiens CDS (233)...(409) 13 aggagctggc ggagggcgtt cgtcctggga gctgcacttg ctccgtcggg tcgccggctt 60 caccggaccg caggctcccg gggcagggcc ggggccagag ctcgcgtgtc ggcgggacat 120 gcgctgcgtc gcctctaacc tcgggctgtg ctctttttcc aggtggcccg ccggtttctg 180 agccttctgc cctgcgggga cacggtctgc accctgcccg cggccacgga ccatgaccat 240 gaccctccac accaaagcat ctgggatggc cctactgcat cagatccaag ggaacgagct 300 ggagcccctg aaccgtccac cttctagaat gtgcctggct agagatcctg atgattggtc 360 tcgtctggcg ctccatggag cacccagtga agctactgtt tgctcctaac ttgctcttgg 420 acaggctttg tggatttgac cctccatgat caggtccacc ttctagaatg tgcctggcta 480 gagatcctga tgattggtct cgtctggcgc tccatggagc acccagtgaa gctactgttt 540 gctcctaact tgctcttgga caggaaccag ggaaaatgtg tagagggcat ggtggagatc 600 ttcgacatgc tgctggctac atcatctcgg ttccgcatga tgaatctgca gggagaggag 660 tttgtgtgcc tcaaatctat tattttgctt aattctggag tgtacacatt tctgtccagc 720 accctgaagt ctctggaaga gaaggaccat atccaccgag tcctggacaa gatcacagac 780 actttgatcc acctgatggc caaggcaggc ctgaccctgc agcagcagca ccagcggctg 840 gcccagctcc tcctcatcct ctcccacatc aggcacatga gtaacaaagg catggagcat 900 ctgtacagca tgaagtgcaa gaacgtggtg cccctctatg acctgctgct ggagatgctg 960 gacgcccacc gcctacatgc gcccactagc cgtggagggg catccgtgga ggagacggac 1020 caaagccact tggccactgc gggctctact tcatcgcatt ccttgcaaaa gtattacatc 1080 acgggggagg cagagggttt ccctgccaca gtctgagagc tccctggc 1128 14 530 DNA Homo sapiens exonexon junction (260)...(261) exon 1Cexon 4 14 gcggccgccg ccaacgcgca ggtctacggt ctgacctgcc tcccctacgg ccccgggtct 60 gaggctgcgg cgttcggctc caacggcctg gggggtttcc ccccactcaa cagcgtgtct 120 ccgagcccgc tgatgctact gcacccgccg ccgcagctgt cgcctttcct gcagccccac 180 ggccagcagg tgccctacta cctggagaac gagcccagcg gctacacggt gcgcgaggcc 240 ggcccgccgg cattctacag aatggtgctg tcatgtggac tgtcctcccg agtgtcccac 300 tggatgttca gagaatttat gtgaaggtca cgtcatttag cattgagatg ctgtggttac 360 cttcttccat ttcttccata atatgcagcc acatctatgt gtgaagaaat gtaatagata 420 aaatttctct ggacgcataa taatgtgaga aagattgtca catgtcccag caaattgtta 480 ttaatataaa tttgttactt ggcaagctga gattttgcaa gatgttactc 530 15 2315 DNA Homo sapiens CDS (241)...(903) exonexon junction (883)...(884) exon 5exon 6 15 gagcccagga gctggcggag ggcgttcgtc ctgggactgc acttgctccc gtcgggtcgc 60 ccggcttcac cggacccgca ggctcccggg gcagggccgg ggccagagct cgcgtgtcgg 120 cgggacatgc gctgcgtcgc ctctaacctc gggctgtgct ctttttccag gtggcccgcc 180 ggtttctgag ccttctgccc tgcggggaca cggtctgcac cctgcccgcg gccacggacc 240 atg acc atg acc ctc cac acc aaa gca tcc ggg atg gcc cta ctg cat 288 Met Thr Met Thr Leu His Thr Lys Ala Ser Gly Met Ala Leu Leu His 1 5 10 15 cag atc caa ggg aac gag ctg gag ccc ctg aac cgt ccg cag ctc aag 336 Gln Ile Gln Gly Asn Glu Leu Glu Pro Leu Asn Arg Pro Gln Leu Lys 20 25 30 atc ccc ctg gag cgg ccc ctg ggc gag gtg tac ctg gac agc agc aag 384 Ile Pro Leu Glu Arg Pro Leu Gly Glu Val Tyr Leu Asp Ser Ser Lys 35 40 45 ccc gcc gtg tac aac tac ccc gag ggc gcc gcc tac gag ttc aac gcc 432 Pro Ala Val Tyr Asn Tyr Pro Glu Gly Ala Ala Tyr Glu Phe Asn Ala 50 55 60 gcg gcc gcc gcc aac gcg cag gtc tac ggt cag acc ggc ctc ccc tac 480 Ala Ala Ala Ala Asn Ala Gln Val Tyr Gly Gln Thr Gly Leu Pro Tyr 65 70 75 80 ggc ccc ggg tct gag gct gcg gcg ttc ggc tcc aac ggc ctg ggg ggt 528 Gly Pro Gly Ser Glu Ala Ala Ala Phe Gly Ser Asn Gly Leu Gly Gly 85 90 95 ttc ccc cca ctc aac agc gtg tct ccg agc ccg ctg atg cta ctg cac 576 Phe Pro Pro Leu Asn Ser Val Ser Pro Ser Pro Leu Met Leu Leu His 100 105 110 ccg ccg ccg cag ctg tcg cct ttc ctg cag ccc cac ggc cag cag gtg 624 Pro Pro Pro Gln Leu Ser Pro Phe Leu Gln Pro His Gly Gln Gln Val 115 120 125 ccc tac tac ctg gag aac gag ccc agc ggc tac acg gtg cgc gag gcc 672 Pro Tyr Tyr Leu Glu Asn Glu Pro Ser Gly Tyr Thr Val Arg Glu Ala 130 135 140 ggc ccg ccg gca ttc tac agg cca aat tca gat aat cga cgc cag ggt 720 Gly Pro Pro Ala Phe Tyr Arg Pro Asn Ser Asp Asn Arg Arg Gln Gly 145 150 155 160 ggc aga gaa aga ttg gcc agt acc aat gac aag gga agt atg gct atg 768 Gly Arg Glu Arg Leu Ala Ser Thr Asn Asp Lys Gly Ser Met Ala Met 165 170 175 gaa tct gcc aag gag act cgc tac tgt gca gtg tgc aat gac tat gct 816 Glu Ser Ala Lys Glu Thr Arg Tyr Cys Ala Val Cys Asn Asp Tyr Ala 180 185 190 tca ggc tac cat tat gga gtc tgg tcc tgt gag ggc tgc aag gcc ttc 864 Ser Gly Tyr His Tyr Gly Val Trp Ser Cys Glu Gly Cys Lys Ala Phe 195 200 205 ttc aag aga agt att caa gaa ctt cca aca cta tgt tga ataggatggt 913 Phe Lys Arg Ser Ile Gln Glu Leu Pro Thr Leu Cys 210 215 220 actggtacca aaacagagat atagaccaat ggaacagaac agagccctca gaaataatac 973 cacacatcta caaccatctg atctttgaca aacgtgacaa aaacaagaaa tggggaaagg 1033 attccctatt taataaatag tgctgggaaa actggctagc catatgtaga aagctgaaac 1093 tggatcactt ccttacacct tatacaaaaa ttaattcaag atggattaaa gacttaaatg 1153 ttagaactaa aaccataaaa accctagaag aaaacctagg caataccatt caggacatag 1213 gcatgggcaa ggacttcatg tctaaaacac caaaagcaat ggcaacaaaa gccaaaattg 1273 acaaatggga tctaattaaa ctaaagagct tctgttcttt gctggggtat ctgaagactg 1333 aaaacacagc aaaagaaact accatcagac tgaacaggca acctacagaa tgggagaaaa 1393 tttttgcaat ctactcatct gacaaagggc taatatccag aatctacaaa gaactcaaac 1453 aaatttacaa gaaaaaagga accccatcaa caagtgggtg aaggatatga acagacactt 1513 ctcaaaagaa gacatttatg cagccaacag acacatgaaa aaatgctcat catcattggc 1573 catcagagaa atgcaaatca aaaccacaat gagataccat ctcacaccag ttagaatggt 1633 gatcattaga aagtcaggaa acgacaggtg ctggagagga tgtggagaaa taggaacact 1693 tttacactgt tggtgggact gtaaactggt tcaaccattg tggaagacag tgtggcgatt 1753 cctcagggat ctacaactag aaataccatt tgacccagcc atcccattac tgggtatata 1813 cccaaaggat tataaatcat gctgctataa agacacatgc acacgtatgt ttattgcggc 1873 actattcaca atagcaaaga cttggaacca acctaaatat ccaacaacaa taggctagat 1933 taagaaaatg tggcacatat acaccatgga atactatgca gccataaaaa aggatgagtt 1993 catatacttg tagggacatg gatgaagctg gaaaccatca ttctcagcaa actattgcaa 2053 ggacaaaaaa ccaaacatgc atgttctcac tcataggtgg gaattgaaca ataagaacac 2113 ttggacacag ggtggggaac attacacact ggggcctgtt gtggggtggg gggagggggg 2173 agggatagca ttaggagata taactaatgt aaatgatgag ttaatgggtg cagcacacca 2233 acatggcaca tgtatacata tgtaacaaac ctgcacattg tgcacatgta ccctagaact 2293 taaagtataa taaaaaatat tt 2315 16 330 DNA Homo sapiens CDS (262)...(330) exonexon junction (191)...(192) exon 1Bexon 3 16 gacaaacaga gatatatcgg agtctggcac ggggcacata aggcagcaca ttagagaaag 60 ccggcccctg gatccgtctt tcgcgtttat tttaagccca gtcttccctg ggccaccttt 120 agcagatcct cgtgcgcccc cgccccctgg ccgtgaaact cagcctctat ccagcagcga 180 cgacaagtaa agtggcccgc cggtttctga gccttctgcc ctgcggggac acggtctgca 240 ccctgcccgc ggccacggac c atg acc atg acc ctc cac acc aaa gca tct 291 Met Thr Met Thr Leu His Thr Lys Ala Ser 1 5 10 ggg atg gcc cta ctg cat cag atc caa ggg aac gag ctg 330 Gly Met Ala Leu Leu His Gln Ile Gln Gly Asn Glu Leu 15 20 17 355 DNA Homo sapiens CDS (287)...(355) exonexon junction (85)...(86) exon 1Aexon 2 17 aacaggctcg aaaggtccat gctcctttct cctgcccatt ctatagcata agaagacagt 60 ctctgagtga taatcttctc ttcaagaaga agaaaactag gaaggagtaa gcacaaagat 120 ctcttcacat tctccgggac tgcggtacca aatatcagca cagcacttct tgaaaaagga 180 tgtagatttt aatctgaact ttgaaccatc actgaggtgg cccgccggtt tctgagcctt 240 ctgccctgcg gggacacggt ctgcaccctg cccgcggcca cggacc atg acc atg 295 Met Thr Met 1 acc ctc cac acc aaa gca tct ggg atg gcc cta ctg cat cag atc caa 343 Thr Leu His Thr Lys Ala Ser Gly Met Ala Leu Leu His Gln Ile Gln 5 10 15 ggg aac gag ctg 355 Gly Asn Glu Leu 20 18 323 DNA Homo sapiens exonexon junction (115)...(116) exon 7exon 9 18 cataacgact atatgtgtcc agccaccaac cagtgcacca ttgataaaaa caggaggaag 60 agctgccagg cctgccggct ccgcaaatgc tacgaagtgg gaatgatgaa aggtggcttt 120 gtggatttga ccctccatga tcaggtccac cttctagaat gtgcctggct agagatcctg 180 atgattggtc tcgtctggcg ctccatggag cacccaggga agctactgtt tgctcctaac 240 ttgctcttgg acaggaacca gggaaaatgt gtagagggca tggtggagat cttcgacatg 300 ctgctggcta catcatctcg gtt 323 19 20 DNA Artificial Sequence Antisense Oligonucleotide 19 gaatttggcc tgtagaatgc 20 20 20 DNA Artificial Sequence Antisense Oligonucleotide 20 cgttatgtcc ttgaatactt 20 21 20 DNA Artificial Sequence Antisense Oligonucleotide 21 aaaggagcat ggacctttcg 20 22 20 DNA Artificial Sequence Antisense Oligonucleotide 22 tcagtgatgg ttcaaagttc 20 23 20 DNA Artificial Sequence Antisense Oligonucleotide 23 tcatggtcat ggtccgtggc 20 24 20 DNA Artificial Sequence Antisense Oligonucleotide 24 agctcgttcc cttggatctg 20 25 20 DNA Artificial Sequence Antisense Oligonucleotide 25 gctccagctc gttcccttgg 20 26 20 DNA Artificial Sequence Antisense Oligonucleotide 26 ttgtacacgg cgggcttgct 20 27 20 DNA Artificial Sequence Antisense Oligonucleotide 27 tagcatcagc gggctcggag 20 28 20 DNA Artificial Sequence Antisense Oligonucleotide 28 tagggcacct gctggccgtg 20 29 20 DNA Artificial Sequence Antisense Oligonucleotide 29 tccaggtagt agggcacctg 20 30 20 DNA Artificial Sequence Antisense Oligonucleotide 30 cgttctccag gtagtagggc 20 31 20 DNA Artificial Sequence Antisense Oligonucleotide 31 gggctcgttc tccaggtagt 20 32 20 DNA Artificial Sequence Antisense Oligonucleotide 32 tctcagcttg ccaagtaaca 20 33 20 DNA Artificial Sequence Antisense Oligonucleotide 33 tgaatttggc gagtaacatc 20 34 20 DNA Artificial Sequence Antisense Oligonucleotide 34 tagcgagtct ccttggcaga 20 35 20 DNA Artificial Sequence Antisense Oligonucleotide 35 cacagtagcg agtctccttg 20 36 20 DNA Artificial Sequence Antisense Oligonucleotide 36 cagtctgatg gtagtttctt 20 37 20 DNA Artificial Sequence Antisense Oligonucleotide 37 ggttgcctgt tcagtctgat 20 38 20 DNA Artificial Sequence Antisense Oligonucleotide 38 ttcacccact tgttgatggg 20 39 20 DNA Artificial Sequence Antisense Oligonucleotide 39 gtctgttcat atccttcacc 20 40 20 DNA Artificial Sequence Antisense Oligonucleotide 40 ctggtgtgag atggtatctc 20 41 20 DNA Artificial Sequence Antisense Oligonucleotide 41 cctgactttc taatgatcac 20 42 20 DNA Artificial Sequence Antisense Oligonucleotide 42 agtttacagt cccaccaaca 20 43 20 DNA Artificial Sequence Antisense Oligonucleotide 43 aggaatcgcc acactgtctt 20 44 20 DNA Artificial Sequence Antisense Oligonucleotide 44 atgtgtcttt atagcagcat 20 45 20 DNA Artificial Sequence Antisense Oligonucleotide 45 atgttggtgt gctgcaccca 20 46 20 DNA Artificial Sequence Antisense Oligonucleotide 46 agggtacatg tgcacaatgt 20 47 20 DNA Artificial Sequence Antisense Oligonucleotide 47 ttggcagctc tcatgtctcc 20 48 20 DNA Artificial Sequence Antisense Oligonucleotide 48 aaaggttggc agctctcatg 20 49 20 DNA Artificial Sequence Antisense Oligonucleotide 49 cttggccaaa ggttggcagc 20 50 20 DNA Artificial Sequence Antisense Oligonucleotide 50 aaggcactga ccatctggtc 20 51 20 DNA Artificial Sequence Antisense Oligonucleotide 51 ccaacaaggc actgaccatc 20 52 20 DNA Artificial Sequence Antisense Oligonucleotide 52 agcatccaac aaggcactga 20 53 20 DNA Artificial Sequence Antisense Oligonucleotide 53 agctccctgt ctgccaggtt 20 54 20 DNA Artificial Sequence Antisense Oligonucleotide 54 gaaccagctc cctgtctgcc 20 55 20 DNA Artificial Sequence Antisense Oligonucleotide 55 tccacaaagc gcaccctctt 20 56 20 DNA Artificial Sequence Antisense Oligonucleotide 56 aggtggacct gatcatggag 20 57 20 DNA Artificial Sequence Antisense Oligonucleotide 57 cagacgagac caatcatcag 20 58 20 DNA Artificial Sequence Antisense Oligonucleotide 58 agcaagttag gagcaaacag 20 59 20 DNA Artificial Sequence Antisense Oligonucleotide 59 ccaagagcaa gttaggagca 20 60 20 DNA Artificial Sequence Antisense Oligonucleotide 60 cctgtccaag agcaagttag 20 61 20 DNA Artificial Sequence Antisense Oligonucleotide 61 gatttgaggc acacaaactc 20 62 20 DNA Artificial Sequence Antisense Oligonucleotide 62 tacactccag aattaagcaa 20 63 20 DNA Artificial Sequence Antisense Oligonucleotide 63 atgtgtacac tccagaatta 20 64 20 DNA Artificial Sequence Antisense Oligonucleotide 64 cttctcttcc agagacttca 20 65 20 DNA Artificial Sequence Antisense Oligonucleotide 65 tggtccttct cttccagaga 20 66 20 DNA Artificial Sequence Antisense Oligonucleotide 66 ttgtccagga ctcggtggat 20 67 20 DNA Artificial Sequence Antisense Oligonucleotide 67 tctgtgatct tgtccaggac 20 68 20 DNA Artificial Sequence Antisense Oligonucleotide 68 aagtgtctgt gatcttgtcc 20 69 20 DNA Artificial Sequence Antisense Oligonucleotide 69 gatcaaagtg tctgtgatct 20 70 20 DNA Artificial Sequence Antisense Oligonucleotide 70 aggtggatca aagtgtctgt 20 71 20 DNA Artificial Sequence Antisense Oligonucleotide 71 ccatcaggtg gatcaaagtg 20 72 20 DNA Artificial Sequence Antisense Oligonucleotide 72 gcctttgtta ctcatgtgcc 20 73 20 DNA Artificial Sequence Antisense Oligonucleotide 73 ggagctctca gaccgtggca 20 74 20 DNA Artificial Sequence Antisense Oligonucleotide 74 ctttaaggtg taccactttc 20 75 20 DNA Artificial Sequence Antisense Oligonucleotide 75 gaagaagagc tggactaccc 20 76 20 DNA Artificial Sequence Antisense Oligonucleotide 76 caacaaaaga attatgttct 20 77 20 DNA Artificial Sequence Antisense Oligonucleotide 77 agcctctcat aattgctgca 20 78 20 DNA Artificial Sequence Antisense Oligonucleotide 78 attctttatt tgaacatcaa 20 79 20 DNA Artificial Sequence Antisense Oligonucleotide 79 ttggaagttc ttgaatactt 20 80 20 DNA Artificial Sequence Antisense Oligonucleotide 80 agcaccattc tgtagaatgc 20 81 20 DNA Artificial Sequence Antisense Oligonucleotide 81 acaaagcctg tccaagagca 20 82 20 DNA Artificial Sequence Antisense Oligonucleotide 82 cgttatgtcc tgtagaatgc 20 83 20 DNA Artificial Sequence Antisense Oligonucleotide 83 ccctggttcc acctttcatc 20 84 20 DNA Artificial Sequence Antisense Oligonucleotide 84 gcgggccact ttacttgtcg 20 85 20 DNA Artificial Sequence Antisense Oligonucleotide 85 ttcttcttct tgaagagaag 20 86 20 DNA Artificial Sequence Antisense Oligonucleotide 86 gcgggccacc tcagtgatgg 20 87 20 DNA Artificial Sequence Antisense Oligonucleotide 87 ccacaaagcc acctttcatc 20 88 20 DNA Artificial Sequence Antisense Oligonucleotide 88 ccctggttcc tgtccaagag 20 89 20 DNA Artificial Sequence Antisense Oligonucleotide 89 agtacctact tgaagagaag 20 90 20 DNA Artificial Sequence Antisense Oligonucleotide 90 aagtgctgag attacagatg 20 91 20 DNA Artificial Sequence Antisense Oligonucleotide 91 cgcgggtacc tgtagaatgc 20 92 20 DNA Artificial Sequence Antisense Oligonucleotide 92 cactattacc ttgaatactt 20 93 20 DNA Artificial Sequence Antisense Oligonucleotide 93 gtcacttacc tgtccaagag 20 94 20 DNA Artificial Sequence Antisense Oligonucleotide 94 tcaactcacc agaattaagc 20 95 20 DNA Artificial Sequence Antisense Oligonucleotide 95 catttcatcc agcattgagt 20 96 20 DNA Artificial Sequence Antisense Oligonucleotide 96 cctttgttac tgtaggtggg 20 97 144 DNA Homo sapiens 97 aaacacaagc gccagagaga tgatggggag ggcaggcctg accctgatgg ccaaggcagg 60 cctgaccctg cagcagcagc accagcggct ggcccagctc ctcctcatcc tctcccacat 120 caggcacatg agtaacaaag gcat 144 98 1218 DNA Homo sapiens 98 agcctggcac gcacgtcctc cgccgagtac aatgtcaaca acctggtgag ccctgtgctg 60 ttccaggagg ccctgtggca cgtgcctgag cacgcggtgg tgctggagat cgcgccccac 120 gccctgctgc aggctgtcct gaagcgtggc ctgaagccga gctgcaccat catccccctg 180 atgaagaagg atcacaggga caacctggag ttcttcctgg ccggcatccg gaggctgcac 240 ctctcaggca tcgacgccaa ccccaatgcc ttgttcccac ctgtggagtt cccagctccc 300 cgaggaactc ccctcatctc cccactcatc aagtgggacc acagcctggc cttgtccctg 360 acggccgacc agatggtcag tgccttgttg gatgctgagc cccccatact ctattccgag 420 tatgatccta ccagaccctt cagtgaagct tcgatgatgg gcttactgac caacctggca 480 gacagggagc tggttcacat gatcaactgg gcgaagaggg tgccaggctt tgtggatttg 540 accctccatg atcaggtcca ccttctagaa tgtgcctggc tagagatcct gatgattggt 600 ctcgtctggc gctccatgga gcacccaggg aagctactgt ttgctcctaa cttgctcttg 660 gacaggaacc agggaaaatg tgtagagggc atggtggaga tcttcgacat gctgctggct 720 acatcatctc ggttccgcat gatgaatctg cagggagagg agtttgtgtg cctcaaatct 780 attattttgc ttaattctgg agtgtacaca tttctgtcca gcaccctgaa gtctctggaa 840 gagaaggacc atatccaccg agtcctggac aagatcacag acactttgat ccacctgatg 900 gccaaggcag gcctgaccct gcagcagcag caccagcggc tggcccagct cctcctcatc 960 ctctcccaca tcaggcacat gagtaacaaa ggcatggagc atctgtacag catgaagtgc 1020 aagaacgtgg tgcccctcta tgacctgctg ctggagatgc tggacgccca ccgcctacat 1080 gcgcccacta gccgtggagg ggcatccgtg gaggagacgg accaaagcca cttggccact 1140 gcgggctcta cttcatcgca ttccttgcaa aagtattaca tcacggggga ggcagagggt 1200 ttccctgcca cagtctga 1218

Claims

What is claimed is:

1. A compound 8 to 50 nucleobases in length targeted to a nucleic acid molecule encoding estrogen receptor alpha, wherein said compound specifically hybridizes with said nucleic acid molecule encoding estrogen receptor alpha and inhibits the expression of estrogen receptor alpha.

2. The compound of claim 1 which is an antisense oligonucleotide.

3. The compound of claim 2 wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO: 19, 20, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 37, 39, 40, 42, 43, 44, 45, 46, 47, 48, 49, 50, 52, 53, 54, 56, 60, 74, 77, 88, 91 or 95.

4. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

5. The compound of claim 4 wherein the modified internucleoside linkage is a phosphorothioate linkage.

6. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

7. The compound of claim 6 wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.

8. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

9. The compound of claim 8 wherein the modified nucleobase is a 5-methylcytosine.

10. The compound of claim 2 wherein the antisense oligonucleotide is a chimeric oligonucleotide.

11. A compound 8 to 50 nucleobases in length which specifically hybridizes with at least an 8-nucleobase portion of an active site on a nucleic acid molecule encoding estrogen receptor alpha.

12. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

13. The composition of claim 12 further comprising a colloidal dispersion system.

14. The composition of claim 12 wherein the compound is an antisense oligonucleotide.

15. A method of inhibiting the expression of estrogen receptor alpha in cells or tissues comprising contacting said cells or tissues with the compound of claim 1 so that expression of estrogen receptor alpha is inhibited.

16. A method of treating an animal having a disease or condition associated with estrogen receptor alpha comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of claim 1 so that expression of estrogen receptor alpha is inhibited.

17. The method of claim 16 wherein the disease or condition is a hyperproliferative disease.

18. The compound of claim 1 targeted to a nucleic acid molecule encoding an estrogen receptor alpha/fatty acid synthase fusion transcript, wherein said compound specifically hybridizes with and differentially inhibits the expression of said fusion transcript relative to variants of estrogen receptor alpha.

19. The compound of claim 1 targeted to a nucleic acid molecule encoding estrogen receptor alpha, wherein said compound specifically hybridizes with and differentially inhibits the expression of one of the variants of estrogen receptor alpha relative to the remaining variants of estrogen receptor alpha.

20. The compound of claim 19 targeted to a nucleic acid molecule encoding estrogen receptor alpha, wherein said compound hybridizes with and specifically inhibits the expression of a variant of estrogen receptor alpha, wherein said variant is selected from the group consisting of ESR-alpha, ESR-alpha-II, ESR-alpha-III, ESR-alpha-IV, ESR-alpha-V, ESR-alpha-VI, ESR-alpha-VII, ESR-alpha-VIII and ESR-alpha-IX.