GB2402391A - Fowlpox recombinant genome - Google Patents

Abstract

The invention relates to recombinant nucleic acids wherein a heterologous nucleic acid sequence is introduced into a viral genome at a naturally occurring deletion site of said genome or at a mutated insertion site present in said genome. The possible deletion sites are identified in Table 2, whilst insertion sites are identified in Table 6. The heterologous gene may also be introduced by replacing a viral gene in which said deletion sites is found. Specific deletion sites are disclosed for the genome of the fowlpox FPV9. Other modified fowlpox viruses claimed are HP-1, US-FPV, FPV-M or avipox, Chordopoxvirus and Poxivirus.

Description

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Background to the Invention

There is a need for new viral vectors for delivery and expression of heterologous nucleic acids. In order to use a viral genome in a vector situation, the heterologous nucleic acids must be incorporated into the viral vector genome.

Viral genomes are very compact with little or no redundant genetic material.

Indeed, many viruses possess almost no intergenic nucleic acid, and often possess single ORFs encoding multiple promoters, bidirectional promoters and even overlapping ORFs. Therefore, it is readily appreciated that choosing a site for insertion of heterologous nucleic acid sequence is extremely difficult since virtually all :. . of the viral nucleic acid can have essential functions, or even multiple essential functions, which would be unsuitable for insertion/deletion. There is thus a need for new viral acceptor loci ('insertion sites') which can tolerate the disruption which ÀÀ À À À insertion of foreign nucleic acid can entail. À. À À.

Prior art technique for locating such sites rely on trial and error. This is a labour intensive and often demoralizing process which only rarely produces a suitable new site or vector.

Other prior art techniques involve exhaustive study of biological function of viral gene(s) in order to try to determine which might be dispersible, yet retain viral integrity. Such techniques are necessarily long-term and can often yield few if any advances, as well as requiring dedication of significant research and development resources with no guarantee of success.

The present invention seeks to overcome problem(s) associated with the prior art.

Summary of the Invention

The invention is based upon the finding that naturally occurring andlor attenuated viral strains can contain deletable genetic material. More in particular, the invention is founded on the surprising finding that viral strains can possess naturally occurring deletions of genetic material without losing viability. Furthermore, it is shown herein that the deletable material may be advantageously replaced by heterologous nucleotide sequence, providing novel viral vectors and viruses.

There are numerous advantages to using naturally occurring deletion sites as insertion sites for the construction of viral vectors according to the invention. These À À include the fact that, as disclosed herein, said deletions are non- essential regions for À viral survival. Furthermore, as disclosed herein, the 'deletion' sites ordinarily comprise tracts of nucleic acid, and are therefore capable of having at least the Rome À À À. 15 quantity of nuleic acid reintroduced to that site without any adverse effects on viral À.- À integrity. Furthermore, since a significant number of the deletions described herein are A. . defined with reference to attenuated viruses, the invention provides additional . advantages in contribution to attenuation of the viral vectors simultaneous with the À.

making of the insertions as described herein.

Thus the present invention provides insertion site(s), viral vector nucleic acids(s) comprising heterologous nucleotide sequence inserted at said sites and viruses comprising said nucleic acids.

Thus, in one aspect the invention provides a recombinant nucleic acid comprising at least part of a viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion being located at a naturally occurring deletion site of said genome, wherein the insertion site is an insertion site selected from table 2, or a homologue thereof.

In another aspect, the invention relates to a recombinant nucleic acid comprising a viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion being located at a naturally occurring deletion site of said genome, wherein the insertion site is an insertion site selected from table 2, or a homologue thereof.

In another aspect, the invention relates to a recombinant nucleic acid as described above, wherein the insertion site is an insertion site selected from deletions 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 20, 22, 23, 24 or 25 of table 2, or a homologue thereof.

In another aspect, the invention relates to a recombinant nucleic acid as described above, wherein the insertion site is an insertion site selected from deletions 2, 6, 7, 8, Àe he : À . 9, 10, 11, 12, 13, 14, 16, 17, 20, 22 or 24 of table 2, or a homologue thereof. À. . À-.e

In another aspect, the invention relates to a recombinant nucleic acid as described À À above, wherein the insertion site is an insertion site selected from deletions 2, 8, 9, 10, Àe À 11, 12, 13, 14, 16, 17, 20, 220r240ftable2,orahomologue thereof. À. À Àe

!., In another aspect, the invention relates to a recombinant nucleic acid as described Àe above, wherein the insertion site is an insertion site selected from deletions 2, 8, 9, 11, 12, 13, 14, 20, 220r240ftable2,orahomologue thereof.

In another aspect, the invention relates to a recombinant nucleic acid as described above, wherein the insertion site is an insertion site selected from deletions 8, 9, 11, 12, 13, 20, 22 or 24 of table 2, or a homologue thereof.

In another aspect, the invention relates to a recombinant nucleic acid as described above, wherein the insertion site is an insertion site selected from deletions 8, 9, 11, 13, 22 or 24 of table 2, or a homologue thereof.

In another aspect, the invention relates to a recombinant nucleic acid as described above, wherein the insertion site is an insertion site selected from deletions 9, 11, 13, 22 or 24 of table 2, or a homologue thereof.

In another aspect, the invention relates to a recombinant nucleic acid as described I above, wherein the insertion site is an insertion site selected from deletions 9, 11, 13, 22 or 24 of table 2, or a homologue thereof.

In another aspect, the invention relates to a recombinant nucleic acid as described above, wherein the insertion site is an insertion site of a medium or long deletion.

In another aspect, the invention relates to a recombinant nucleic acid as described above, wherein the insertion site is an insertion site of a long deletion. i : .' In another aspect, the invention relates to a recombinant nucleic acid as described see.

We above, wherein the viral genome is not an FP9 viral genome, and the insertion is located at a site homologous to a naturally occurring FP9 deletion site as defined in . À' ;' 15 any preceding claim.

- . . , : In another aspect, the invention relates to a recombinant nucleic acid comprising a À À., viral genome, said viral genome comprising an insertion of a heterologous nucleotide e e.

sequence into the viral genome, said insertion site comprising a deletion of a viral gene, wherein the gene is selected from table 2 or table 3, or a homologue thereof.

In another aspect, the invention relates to a recombinant nucleic acid comprising a viral genome, said viral genome comprising an insertion of a heterologous nucleotide i sequence into the viral genome, said insertion site comprising a deletion of a viral gene, wherein the gene is selected from table 2 or table 3, or a homologue thereof, but is not FPV054, 115, 219, 220, 221, 222, 241-247, or type A inclusion protein.

In another aspect, the invention relates to a recombinant nucleic acid comprising a] viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion site comprising a deletion of a viral i gene, wherein the gene is selected from table 2 or table 3, or a homologue thereof, but is not FPV001, 054, 115, 171, 219, 220, 221, 222, 241-247, or type A inclusion protein. I In another aspect, the invention relates to a recombinant nucleic acid as described above wherein the heterologous nucleotide sequence comprises and is capable of supporting expression of an antigen. Preferably the antigen is a cancer or disease antigen selected from table 4.

In another aspect, the invention relates to a recombinant nucleic acid as described above wherein the viral genome is or is derived from a Poxvirus.

: À . ' In another aspect, the invention relates to a recombinant nucleic acid as described above wherein the viral genome is or is derived from a Chordopoxvirus.

In another aspect, the invention relates to a recombinant nucleic acid as described o. . À above wherein the viral genome is or is derived from an Avipox virus. see: re

- In another aspect, the invention relates to a recombinant nucleic acid as described above wherein the viral genome is or is derived from a Fowlpox virus.

In another aspect, the invention relates to a recombinant nucleic acid as described above wherein the viral genome is or is derived from a Fowlpox virus strain selected from HP-1, US-FPV, FPV-M or FP9. i In another aspect, the invention relates to a recombinant nucleic acid as described above wherein the viral genome is or is derived from a Fowlpcx virus strain FP9.

In another aspect, the invention relates to a recombinant nucleic acid as described I above wherein the viral genome is or is derived from a virus mentioned in Table 3.

In another aspect, the invention relates to a recombinant poxvirus comprising a nucleic acid molecule as described above.

In another aspect, the invention relates to a recombinant nucleic acid comprising a viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion being located at a naturally occurring deletion site of said genome.

In another aspect, the invention relates to a recombinant nucleic acid comprising a viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion being located at a naturally occurring mutant insertion site of said genome. Preferably said insertion site is selected from

table 6. À. Àe À À -

À Detailed Description of the Invention À .

Viral genoma À:e : US-FPV is a wild-type Fowlpox virus which has been sequenced. Webster's strain . FPV-M is an attenuated form of this virus. À.

HP-1 is a European wild-type Fowlpox virus. FP9 is an attenuated form of this virus.

The complete FP9 genome is provided herein.

Fowlpox strain FP9 was derived by 438 passages through CEFs in tissue culture from the virulent wild-type Fowlpox HP-1 strain and then plaque purified.

26 deletions are present in FP9 which are not present in US wild-type (US FPV).

7 of these 26 deletions are present in the European wild-type (HP-1). The 19 of these deletions which are absent from both the US and European wildtype Fowlpox strains are particularly preferred. Of these 19 deletions, the 15 which are demonstrated to be absent from Webster's strain are especially preferred. The remaining 4/19 deletions are absent from at least US FPV and HP-1.

Thus, in a preferred embodiment, the insertion site(s) according to the invention are preferably the 15/19 deletions which are confirmed to be absent from US wild-type (US FPV), European wild-type (HP-1) and Webster's FPV-M.

The deletions have been numbered 1-26 (see table 2). The 15 which have been sequenced against Webster's are deletions 2, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 20, 22 and 24. Their size and the genes they affect are listed in Table 1. Thus, in a preferred embodiment the insertion site is or is defined by FP9 deletions 2, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 20,220r240ftable2.

FP9 Deletions as insertion sites À c. 15 If a virus is stable when a deletion is present then the virus must be able to function without that particular length of DNA. According to the present invention, a foreign (heterologous) sequence can be inserted into the deletion site. Advantageously this À. occurs without further destabilizing the virus. Àe

À . 20 Referring to Table 1, specific examples of deletions are presented. For example, the column entitled 'FP9vUSmutl gives the position in FP9. Further details are presented throughout the table, such as in the comment column. Further examples and details are provided in table 5, including commentary and guidance on suitability or special considerations when putting the invention into practice in individual cases.

Size of the deletion The larger the deletion the more likely it is to be a suitable insertion site. Therefore most preferred insertion sites are those defined by the largest deletions.

A relatively long DNA sequence may advantageously be inserted according to the present invention so it is preferred to insert it at a point which previously held a long strand DNA.

SMALL Number Base Pairs deleted < 6 MEDIUM 6 < Number Base Pairs deleted < 100 LARGE 100 < Number Base Pairs deleted Thus, preferred insertion sites are those defined by medium deletions, more preferred insertion sites defined by large deletions. These are disclosed in table 2, and are discussed in more detail below.

Small deletions and associated genes: À À c I. À Deletion 6= lbp :. . Deletion 6 destroys FPV054 = D9R, Mut T protein À This gene is in a non-essential site in Fowlpox virus and thus a preferred insertion site.

The D8 and D9 genes represent preferred insertion sites, especially preferred in À. À À

À. À Fowlpox. À.e

À . 20 Deletion 7 = 4bp Deletion 7 also destroys FPV054 = D9R, Mut T protein This deletionlgene is a preferred insertion site, especially preferred in Fowlpox viruses.

Deletion 8= lop Deletion 8 knocks out of FPV070 = mus musculus T10 gene homologue, a gene involved in embryogenesis. This represents a preferred insertion site.

Deletion 14 = 3bp Deletion 14 makes a point mutation in FPV171 (early transcription factor VETFL).

This is the homologue of the vaccinia A8L gene which is essential for virus morphogenesis. Because of the risk of disrupting an essential gene, appropriate care would need to be taken in using this as an insertion site.

Deletion 16= 2bp Deletion 16 shortened an A-type inclusion protein, A25L. This is arguably related to Deletion VI in MVA, but is different from this MVA deletion. This is especially preferred in fowlpox viruses.

Deletion 17= lbp Deletion 17 shortened an A-type inclusion protein, A25L. This is arguably related to Deletion VI in MVA, but is different from this MVA deletion. This is especially preferred in fowlpox viruses. À À. : À

Deletion 20 = lbp . IS Deletion 20 lengthens FPV213 TM protein. The function of this protein is not known and it must be borne in mind that elongation of the protein may affect its function in À.. FP9. Therefore, because of the risk of disrupting this gene function, appropriate care would need to be taken in using this as an insertion site. À a.

À. 20 Deletion 26=1bp Deletion 26 is small.

Since it does not interrupt an ORF it is a good site.

Medium deletions: Deletion 10 = 17bp Deletion 10 splits the FPV1 IS (M1L) Ankyrin repeat in two. M1L is one of the deleted genes in MVA deletion II, but MVA deletion II is different from deletion 10 of the present invention. This is especially preferred in fowlpox/avipox viruses, especially in fewlpox viruses.

Deletion 12 = 23bp This is a deletion of an intergenic region. The deletion is located immediately downstream of the TAA termination codon for the P35 gene, FPV140 (H3L an IMV membrane associated protein). The H3L gene is non-essential but deletion of this gene may cause reduced plaque size and/or virus yield. There would therefore be a risk that insertion of a cassette into Deletion 12 would interfere with the expression of FPV140.

If reduced FPV140 gene expression produced the same phenotype in FPV as does reduced H3L expression in VACV. These considerations should be taken into account when using deletion 12 as an insertion site.

Large deletions: Deletion 2 = 1534bp Deletion 2 deletes FPV001 in addition to a promoter from FPV002. The site is diploid. À

Insertion into the first gene is possible but success rates can be variable as the site is Àe

often unstable. À À. À À À.

À Deletion 9 = 5831bp Deletion 9 does not delete ORFs in FP9. This is an unusual site and a large deletion. À À

À The genome structure differs between FP9 and US FPV. À

À. 20 Deletion 9 is a preferred insertion site.

The FPWS strain has B22R serpin homologue genes. A number of these are deleted in MVA (although B22R itself is not). Insertion into FPWS FPV097 is also provided according to &e present invention.

The site is most preferred for European strains of FPV, most preferably for FP9.

Deletion 11 = 3426bp Deletion 11 deletes FPV124 (NlR/p28 family) and &e 5prime part of FPV125 (v type Ig domain, function unknown). Neit&er of &ese genes has homologues in vaccinia but they do in the US FPV strain. N1R has been shown to be a virulence factor in ectromelia virus and is in Shope virus.

This is an advantageous insertion site because it is large, and because it is in a new genomic region.

This is a highly preferred site.

Deletion 13 = 2187bp Deletion 13 knocks out FPV159 0NlR/p28 family) and FPV160 (unknown).

This is a highly preferred site. Àa Àe À À

Without wishing to be bound by theory, this part of the FPV genome being almost À 15 totally made up of these gene families, deletion of FPV150toFPV163 may be used as : . an insertion site. Thus, in another embodiment, FPV150-FPV163 form an insertion site.

À. This is backed by the deletion of almost all the Anlyrin repeat families in Deletion 24 À.- ÀÀ. 20 (present in FPV but absent from the VACV genome). Given the disruption of the M1L Ankyrin-like gene by Deletion 10, it follows that in another embodiment the invention relates to use of Ankyrin repeat family members as insertion sites. In a further embodiment, ankyrin repeat genes may be used an insertion site(s) singly or in combination.

Deletion 22 = 2942bp Deletion 22 deletes FPV219 (Ankyrin), FPV220 and FPV221 (both unknown) and FPV222 (Ankyrin). As mentioned above when discussing Deletion 13, many Ankyrin genes are unique to FPV.

This is a preferred insertion site.

This site is especially preferred for fowlpox viruses, especially FP9.

Deletion 24 = 9334bp Deletion 24 deletes FPV241-FPV246 (all Anlyrin repeat family members) and FPV247 (Efc family). As mentioned above when discussing Deletion 13, many Anlyrin genes are unique to FPV.

Use of unique anlyrin genes as insertion sites is preferred, especially preferred in fowlpox, preferably FP9.

Deletion 24 is particularly preferred for fowlpox, preferably for FP9. Be Àe À À À- À . 15

2.. Heterologous nucleoffde sequence À-e À: This term has its natural meaning in the art, and may also nclude exogenous À. homologous material ea. material from the same or a similar viral strain, but À.- recombined into a new position ofthe target genome.

Preferably the heterologous nucleotide sequence comprises coding sequence capable of being expressed in the target cell. Expression may be produced by use of any suitable promoter known to those sldlled in the art.

Preferably the heterologous sequence comprises antigen encoding sequence.

Preferably the antigen encoded is derived from or associated with a cancer and/or an infectious disease. Examples of preferred cancer(s) and infectious disease(s) are given in Table 4 below. Preferably the antigen encoded comprises at least part of one or more of the antigens given in Table 4, preferably the antigen encoded comprises one or more of the antigens given in Table 4.

Inserffon sites In a broad aspect, insertion sites according to the present invention may be seen as viral genetic loci which comprise naturally occurring deletion(s), preferably in a viral gene. Preferably said deletion(s) are in the coding sequence of a gene, but may equally be in a non-coding (intergenic) region. Such a non-coding region may be a promoter region.

Preferably, the term 'insertion sites' comprises equivalents thereto in diverse viral species, andlor may include expanded deletions as explained below.

In a preferred embodiment, insertion sites are comprised in table 3.

In a highly preferred embodiment, insertion sites are comprised in table 2. À

More preferably, insertion site(s) are individual sites selected from table 2 as explained À

above in the summary of the invention. À-e

In another aspect, genes known to contain a naturally occurring deletion may themselves be wholly deleted and thereby form an insertion site according to the r À invention. This advantageously permits insertion of a greater quantity of . 20 exogenouslheterologous nucleic acid into said insertion site. Without wishing to be bound by theory, one reason for doing this is that the presence of a deletion in a particular gene may be an indicator of loss of function andlor redundancy and therefore permit an insertion site to be advantageously expanded according to the present invention.

In another aspect, the invention relates to insertion site(s) according to the present invention which are viral genetic loci which comprise naturally occulting mutant insertion(s), preferably in a viral gene. Without wishing to be bound by theory, the finding of a naturally occurring mutant insertion at a particular locus may indicate that that locus is tolerant of nucleic acid insertions at that point, and therefore it would be useful as an insertion site according to the present invention. Examples of preferred insertion sites according to this aspect of the invention may be found in table 6 which lists naturally occurring mutant insertion sites which are preferably used as insertion sites according to the present invention.

Insertion sites in genetically diverse viruses The insertion sites of the present invention may be utilised in any suitable virus. A suitable virus is any virus which possesses a genetic equivalent to one or more of the insertion site(s) of the present invention. Preferably the insertion sites are used in poxviruses, preferably in chordopoxviruses, preferably in orthopox and/or in avipox viruses, preferably in avipox viruses, preferably in fowlpox viruses, preferably in fowlpox strain HP-1, most preferably in fowlpox strain FP9. In some embodiments, the virus may be a homologue of one or more of these viruses.

A number of the examples given relate to FP9. However, it will be appreciated . by the person skilled in the art that FP9 is a convenient example of poxviruses generally, in particular of chordopoxviruses, in particular of avipox viruses, and in particular of fowlpox viruses.

It is well within the ability of one of ordinary skill in the art to identify the insertion sites of the present invention in different members of these and other viral À À families. For example, in Table 3 are presented exemplary equivalents of preferred insertion sites according to the present invention from a selection of diverse viruses. It is demonstrated that these sites are easily located in other viruses using the guidance presented herein.

Referring specifically to Table 3 for the purposes of illustration, these equivalent genes are identified using the BLAST sequence comparison tool.

The BLAST search is carried out using the "Standard nucleotide nucleotide BLAST,' search on the NCBI Nucleotide website: htto://www.ncbi. nlm.nih.ov/blast.

The relevant genes were located within the genome of the US FPV. The DNA sequence was then used to search the BLAST database. The higher the score, the better the snatch. Obviously Fowlpox appeared as the best match in each case with a score of approximately 2000 and an Expect value close to zero. Thus, in one embodiment, the BLAST score is an indicator of equivalence in accordance with table 3.

The search was limited to viruses and an expect value (E) of 5. The poxviruses (excluding Fowlpox) were noted and listed in table 3.

The Expect value (E) is a parameter that describes the number of hits one can "expect" to see just by chance when searching a database of a particular size. It decreases exponentially with the Score (S) that is assigned to a match between two sequences.

Essentially, the E value describes the random background noise that exists for matches between sequences. For example, an E value of 1 assigned to a hit can be interpreted as meaning that in a database of the current size one might expect to see 1 match with a similar score simply by chance. This means that the lower the E-value, or the closer À À it is to "O" the more "significant" the match is. However, keep in mind that searches À - À 15 with short sequences, can be virtually indentical and have relatively high EValue. This : . is because the calculation of the E-value also takes into account the length of the Query sequence. This is because shorter sequences have a high probability of occuring in the database purely by chance. For more details please see the calculations in the À. BLAST materials.

À - ..

À . 20 The Expect value can also be used as a convenient way to create a significance threshold for reporting results. You can change the Expect value threshold on most main BLAST search pages. When the Expect value is increased from the default value of 10, a larger list with more lowscoring hits can be reported.

Alternatively, insertion sites may be identified by reference to sequence homology. In this context sequence homology can be regarded as sequence identity. Exemplary values indicating that the equivalent site had been found in diverse species are at least 50% amino acid sequence identity within avipox viruses, or at least 24% amino acid sequence identity within poxviruses. Further guidance may be obtained from table 3.

Alternatively, BLAST scores may be used to identify insertion sites. Exemplary values indicating that the equivalent site had been found in diverse species are at leasta blast score of 35, preferably a score of 40, preferably even more, such as a score in the thousands for near perfect matching. Exemplary values may be derived from table 3.

In the present case, the sites identified in this manner indicate the locations of the insertion sites according to the present invention in other viruses such as those mentioned in Table 3.

Further fine mapping of the insertion sites is easily accomplished as necessary by direct comparison of the sequence of the exemplary insertion sites with the sequence of the target virus. This comparison may be accomplished using sequence comparison tools such as BLAST, or by simple comparison by eye, thereby enabling the design of primers, choice of restriction sites or other such considerations which are part of the À À. 15 ordinary process of making recombinant nucleic acid constructs. Thus it is apparent that standard recombinant nucleic acid technology may be used to construct the nucleic acids and viruses of the invention as described herein. À.

À Thus in a preferred embodiment, in order to work the invention in a given virus, first À. 20 the insertion site of interest is chosen from those described herein, then the deleted nucleotides are inferred by comparison of the immediate flanking sequences to the publicly available US-FPV (Afonso et al 2000 J.virol 74(8)pp3815-31). The nucleotide sequence 'sandwiched' between the flanking sequences is the 'deleted' sequence which gives rise to an insertion site according to the present invention. This sequence is then used as a query in a sequence comparison technique such as BLAST and compared with the target viral sequence. Naturally, these inferred 'deleted' nucleotides may be used in conjunction with nucleotide sequences flanking the deletion as necessary to produce a sufficiently long probe sequence for searching.

This comparison shows the equivalent site in the target virus which corresponds to the insertion site of interest. Further fine detailedsequence mapping can easily be carried out ea. by eye level sequence comparison in order to design primers, choose restriction 1' sites and suchlike for the construction of a nucleic acid or virus according to the present invention.

Thus is will be appreciated that insertion sites according to the present invention are defined in viral genome(s) other than FP9 by comparison of the FP9 viral genome to said viral genome(s). I For convenience, tables 2 and 3 present numerous examples of insertion sites according to the present invention, and table 3 in particular presents insertion sites from a range of diverse viruses according to the present invention.

Naturally the reader will appreciate that the teachings regarding the location of insertion sites according to the present invention in genetically diverse viral species; apply equally to deletion sites per se, gene deletion sites or mutant insertion sites as À 15 described herein. Equally, the location of gene deletion sites may equally be applied :. . to the location of gene insertion sites, that is to say viral gene(s) which could be used as insertion sites due to the fact that the naturally occurring mutant insertions occur in those gene(s) which may indicate loss of function and/or redundancy as appropriate À. and therefore infer suitability as an insertion site according to the present invention.

À . 20

Brief description of the figures

Figures 1, la, 2 and 2a show a plasmid maps.

Figure 3 shows a diagram.

In addition, the sequence listing shows a number of sequences.

SEQ ID NOs 1-8 show primers SEQ ID NO 9 shows the sequence of the FP9 viral genome SEQ ID NO 10 corresponds to sequence for the basic deletion plasmid pl8dl3 (without foreign genes or promoters). I SEQ ID NO 11 corresponds to sequence for the basic deletion plasmid P18d9 (without promoters or foreign genes).

Examples

Example 1: Construction of vector plasmidforinsertioninto Deletion 13.

Novel plasmids were constructed to enable the generation of recombinant FP9 fowlpox.

Insertion of foreign genes was targeted precisely to to the site of the naturally occurring deletion 13 in the FP9 genome. Sequences of FP9 DNA flanking the site of a 2187bp deletion located at basepair number 180256 of the FP9 genome sequence (SEQ ID NO 9) were amplified by PCR and cloned into the multiple cloning site of plasmid pUC18. The primers for the left 1500bp flank were 5'- CTC GCA TGC ATG ATT ATG TTA TTG À AAT GTA TAG-3' (SEQ ID No:l) and 5'- GTC CTG CAG GTT CGT GCA CCG TAT TCT TCT TTA-3' (SEQ ID NO:2) (sites for restriction enzymes Sphl and PstI are À underlined).The primers for the right 1500bp DNA flank were 5'- GTG TCT AGA AAA GAC AAA CGT GGT TAT AAA CAA-3' (SEQ ID NO:3) and 5'- GTG GGT À. ACC GAG AAT ATA GTA ACA TTT ATA CTC-3' (SEQ ID NO:4) (sites for the restriction enzymes XbaI and KpnI are undalined. These flanks wae then À À À À. ' 20 introduced sequentially, (Right DNA Flank, then Left DNA Flank) into the Àea À - À. .. multiple cloning site of pUC18 to make pl8dl3. To construct a vector plasmid that allows isolation of recombinant FP9 using the reporta enzyme beta-galactosidase, the 5467bp EcoRI-DraI fragment from the fawlpox shuttle vector, pEFL29, (Y.

Qingzhong et al (1994) Vaccine 12 (6) pages 569-573) was blunt ended and insated into the blunted SalI restriction site of pl8dl3 to make pl8dl3Z. The introduced Escherichia cold LacZ gene is unda the control of the fowlpox virus late promoter P4b. This inserted fragment from pEFL29 also contains the vaccinia virus P7.5 early promoter upstream of a unique SmaI site for the insertion and expression of foreign genes in the FP9 genome.

Example 2: Construction and Characterisation of Recombinant Virus AFOX3. Mel3 A PstI fragment of DNA of approximately 338bp containing a synthetic epitope string of melanoma-associated antigens was cut from the expression plasmid pSG2.Mel3 (Mj Palmowski et al 2002 J. Immunol 168 pages 4391-4398), blunted with Klenow and T4 DNA polymerases, and ligated into the unique SmaI site of pl8dl3Z to make the plasmid transfer vector pl8dl3.Mel3. The plasmid pl8dl3.Mel3 that directs the insertion of foreign genes into the site of deletion 13 of the FP9 genome was used to generate the recombinant virus AFOX3.Mel3.

The method for making the recombinant FP9 was essentially as described in Y. Qingzhong et al (1994) Vaccine 12 (6) pages 569-573, except that the plasmid transfer vector was purified using a Qiagen Plasmid Maxi Kit according to the manufacturer's protocol, and the recombinant virus plaques were screened with the colourigenic substrate, Xgal, as described in MEG Boursnell et al (1990) Veterinary Microbiology 23 Pages 305-316. À Àe À e

Example 3: Construction and Characterisation of Recombinant Virus AFOX3. HBs À À. À À À.

A HindIII-NsiI fragment containing the small and middle forms of the Hepatitis B Surface Antigen protein was cut from the expression plasmid pCMVS2.S (M-L À À À. À Michel et al 1995 Proc Natl Acad Sci USA 92 pages 5307-5311), blunted with À.e . 20 Klenow and T4 DNA polymerases, and ligated into the unique SmaI site of pl8dl3Z to make the plasmid transfer vector pl8dl3.HBs. The plasmid pl8dl3.HBs that directs the insertion of foreign genes into the site of deletion 13 of the FP9 genome was used to generate the recombinant virus AFOX3.HBs.

The method for making the recombinant FP9 was essentially as described in Y. Qingzhong et al (1994) Vaccine 12 (6) pages 569-573, except that the plasmid transfer vector was purified using a Qiagen Plasmid Maxi Kit according to the manufacturer's protocol, and the recombinant virus plaques were screened with the colourigenic substrate, Xgal, as described in MEG Boursnell et al (1990) Veterinary Microbiology 23 Pages 305-316.

Example 4: Construction of plasrnd for insertion into Deletion 9.

Novel plasmids were constructed to enable the generation of recombinant FP9 fowlpex.

Insertion of foreign genes was targeted precisely to to the site of the naturally occurnog deletion 9 in the FP9 genome. Sequences of FP9 DNA flanking the site of a 5831bp deletion located at basepair number 101431 of the FP9 genome sequence SEQ ID NO 9) were amplified by PCR and cloned into the multiple cloning site of plasmid pUC18. The primers for the left 1500bp flank were 5'- GTG GAG CTC AAC CAT GTA TTT TCA TCA TCT GTA -3' (SEQ ID No:5) and 5'- GTG GOT ACC CAT AAT AGA ATT ACC TTT GGC CGA -3' (SEQ ID NO:6) (sites for restriction enzymes SacI and KpnI are underlined) .The primers for the right 1500bp DNA flank were 5'- GTC CTG CAG CCA TCT TTA TCA CCT ACG GCT ACA -3' (SEQ ID NO:7) and 5' CTC GCA TGC TTC TAG CGA TAC AGA GTC TGA TGT -3' (SEQ ID NO:8) (sites for the restriction enzymes PstI and Sphl are underlined. These flanks were ee ee : À .. then introduced sequentially, (Left DNA Flank, then Right DNA Flank) into the À 15 multiple cloning site of pUC18 to make pl8d9. To construct a vector plasmid that allows isolation of recombinant FP9 using the reporter enzyme beta-galactosidase, À - the 5477bp EcoRI-DraI fragment from the fowlpox shutBe vector, pEFL29P, a À.

transfer plasmid made previously by the replacement of the unique SmaI site of : pEFL29 (Y. Qingzbong et al (1994) Vaccine 12 (6) pages 569-573) with a PmeI linker (NEB #1177S), was blunt ended and inserted into the blunted SalI restriction site of pl8d9 to make pl8d9Z. The introduced Escherichia cold LacZ gene is under the control of the fowlpox virus late promoter P4b. This inserted fragment om pEFL29 also contains the vaccinia virus P7. 5 early promoter upstream of the unique PmeI site for the insertion and expression of foreign genes in the FP9 genome.

Example 5: Construction and Characterisation of Recombinant Virus AFOX4. Mel3 A PstI fragment of DNA of approximately 338bp containing a synthetic epitope string of melanoma-associated antigens was cut from the expression plasmid pSG2.Mel3 (Mj Palmowski et al 2002 J. Immunol 168 pages 43914398), blunted with Klenow and T4 DNA polymerases, and ligated into the unique PmeI site of pi 8d9Z to make the plasmid transfer vector pi 8d9.Mel3. The plasmid pi 8d9.Mel3 that directs the insertion of foreign genes into the site of deletion 9 of the FP9 genome was used to generate the recombinant virus AFOX4.Mel3.

The method for making the recombinant FP9 was essentially as described in Y. Qingzhong et al (1994) Vaccine 12 (6) pages 569-573, except that the plasmid transfer vector was purified using a Qiagen Plasmid Maxi Kit according to the manufacturer's protocol, and the recombinant virus plaques were screened with the colourigenic substrate, Xgal, as described in MEG Boursnell et al (1990) Veterinary Microbiology 23 Pages 305-316.

Example 6: Construction and Characterisation of Recombinant Virus AFOX4. HBs A HindIII-NsiI fragment containing the small and middle forms of the Hepatitis B Surface Antigen protein was cut from the expression plasmid pCMVS2.S (M-L a Michel et al 1995 Proc Nell Acad Sci USA 92 pages 53075311), blunted with Klenow and T4 DNA polymerases, and ligated into the unique PmeI site of pl8d9Z to make the plasmid transfer vector pl8d9.HBs. The plasmid pl8d9.HBs that directs the insertion of foreign genes into the site of deletion 9 of the FP9 genome was used to generate the recombinant virus AFOX4.HBs.

À. À. 20 The method for making the recombinant FP9 was essentially as described in Y. Qingzhong et al (1994) Vaccine 12 (6) pages 569-573, except that the plasmid transfer vector was purified using a Qiagen Plasmid Maxi Kit according to the manufactura's protocol, and the recombinant virus plaques were screened with the colourigenic substrate, Xgal, as described in MEG Boursnell et al (1990) Veterinary Microbiology 23 Pages 305-316.

All publications mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described methods and systems of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the presant invention. Although the present invention has bean described in connection with specific prepared embodiments, it should be understood that the invantion as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in virology, molecular biology, and biotechnology or related fields are intended to be within the scope of the following clauns. e.. a e. ha Marc :e a a Ma area aces

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Table 2 contd: The six deletions which occur in both FP9 and HP-1 but not US-FPV Deletion No 1 144 1 1 3 11719 1 1 212069 2 18 214219 3 19 218749 2 21 231411 27 26 265992 1 These deletions are due to differs ces in linea! Be between the US-FPV and HP-1 rather than attenuation.

Table 2 contd:

The four delet ions which occur i FP9 whic h have not been sequenced against Webster's Deletion No Position in FP9 Size (bp) Comment 4 32425 15 Possible insertion site but small and minor effect on ORE as exactly 3 amino acids have been deleted 33708 1 Possible insertion site but small and causes only a minor frame shift 23 240466 Not particularly good as small and in an intergenic region À e À 25 262163 1534 Potential insertion site but it is diploid and near the e À terminus so could be risky These deletions occur in FP9 but n at US-FPV fir HP-1. They may occur in À À e. À À Àe À: Àe À . Àe Àe À À. Has

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O Q Q O Q Q Q Q O N

2 0 N N N N N N N _ _ À E E G G G G G G G a: ,, N G G G O 0 c n _ N Ct. N N N N N N N N N a, a) |!; 0 |t |CD|aD t ha 5t N _ G G G D G G G G G _ O _ 0' ) 21 - | | - | - 1 ,2L 32 s s s il -- 0(ó -,0 2 2 2 2 -_, 1I To T O;E ?F; N N N N O O it --N-C N (0 hi ikl l E E E 1. l ^= nits Al 1o _= "n _O N N EN N 0 0 S _ n n n N N N N N N N N N N N I IN O I O 1 1 1 l 1 1 ID O O O N ---|! --- NI |N N N N i N N N N N N N JI N N N 1 O O 41 N N N N

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! th:ist)T r lo _ _ _ N N 11 ;J] A - O - - - - - - - 1O to 10 lo,0 ID ID ID O O O O 1O O, O O, O O O O O s a a a 0O ID em N N | N N N N N | N N | N N N N N N N N N Nl N N N Nl NIN N N IN O U. 10) U) ;55 D D N ÀD D:, N N |N N N N N N N N N N L _ _ _ 1 _ _ _ IL _ _ _ _ _ _ Table 4:Example Antigens Cancer Associated Antigen BreasVOvarian c-ERB2 (Her2/neu) Breast MUC-1 Breast HER2 Breast CEA BreasVColorectaUBurkitPs Iymphoma p53 Burkitt's Iymphoma/Hodgkin's Iymphoma EBNA-1 Burkits Iymphoma/Hodgkin's Iymphoma EBNA-2 Burkits Iymphoma/Hodgkin's Iymphoma EBNA-3 Burkitt's Iymphoma/Hodgkin's Iymphoma EBNA-3A Burkitts Iymphoma/Hodgkin's Iymphoma EBNA-3C Burkitt's Iymphoma/Hodgkin's Iymphoma EBNA4 BurkitPs Iymphoma/Hodgkin's Iymphoma EBNA-6 BurkitPs Iymphoma/Hodgkin's Iymphoma EBV BurkitPs Iymphoma/Hodgkin's Iymphoma EBV LMP2A Cervical HPV 16 E6 Cervical HPV 16 E7 Cervical HPV 18 E6 Cervical HPV 18 E7 Colon CEA Colon MUC-1 Colon MAGE-12 Colon mutant P53 EBV-induced B and T cell Iymphomas EBNA1 EBV-induced B and T cell Iymphomas EBNA2 EBV-induced B and T cell Iymphomas LMP 1 Lung LRP(Lung Resistance Protein) Melanoma BAGE 2-10 Melanoma GAGE-1 Melanoma gp75 Melanoma MAG Melanoma MAGE-1 Melanoma MAGE-2 Melanoma MAGE-3 Melanoma MAGE-4b Melanoma MAGE-5 Melanoma MAGE-6 Melanoma MART-1/Melan-A Melanoma MUM-1-B Melanoma Pmel 17(gp100) Melanoma Tyrosinase Pancreatic/BreasVOvarian MUC- 1 Prostate PSA (prostate specific antigen) Renal HER2neu Renal RAGE Renal MUC-1 multiple CEA multiple Bc1-2 multiple Ki-67 Disease HPV E1-8 (viral protein) 3Z HPV L1(viral protein) HPV L2 (viral protein) HSV go (viral protein) HSV gH (viral protein) HSV gK (viral protein) HSV GG (viral protein) HSV go (viral protein) HBV HBV surface antigen HBV HBV core antigen HCV HCV core protein HCV HCV envelope protein HCV NS2 region HCV NS3 region HCV NS4 region HCV NS5 region e Àe À À À free a.ee À e a À a Àee' e Àe À ea e -a. À Àe

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SEQUENCB LISTING

SEQ ID NO.1

CTC GCA TGC ATG ATT ATG TTA TTG AAT GTA TAG

SEQ ID NO.2

GTC CTG CAG GTT CGT GCA CCG TAT TCT TCT TTA

SEQ ID NO.3

GTG TCT AGA AAA GAC AAA CGT GGT TAT AAA CAA

SEQ ID NO.4

GTG GGT ACC GAG AAT ATA GTA ACA TTT ATA CTC

SBQ ID NO.5

GTG GAG CTC AAC QT GTA TTT TCA TCA TCT GTA

SEQ ID NO.6 GTG GGT ACC CAT AAT AGA ATT ACC m GGC CGA SEQ ID NO.7

GTC CTG CAG CCA TCT TTA TCA CCT ACG GCT ACA

SEQ ID NO.8.

CTC GCA TGC TTC TAG CGA TAC AGA GTC TGA TGT

SEQ ID NO. 9 À À À 1 acactcatat taegatgagt atttatatag tsaaaaaast gtatsaacag tacattccaa 61 aacactsata tacacattat tttaccactt astttgttsa ggtgtsaast acacactatt 121 aaastatata ttattgtttt astsaaaaaa accatacggt tttacataaa atsatactat . 181 atatsatttc cttcaggsaa atattttata aagatacaca aegttagaga aaaacttttt À. 241 tatcgagagc tagagttata gsaaaegttt ttatagagat ttagaaaagc ttttttatag 301 agagatagag ttatagsaaa acttttttat cgagagatag agttatagea aaegttttta À 361 tagagatttc gsaaagattt tttatcgaga gatagagtta tagsaaaact tttttataga 421 gagatagagt tatagsaaaa cttttttatc gagatttaga aaagattttt tttatagaga 481 gatagagtta tagsaaaact ttttatagag agatagagtt atagaaaaac ttttttatag À 541 agagatagag ttatagsaaa agtttttatc gagatttaga aaagattttt tatagagagc À . 601 tagagttata gaaaaacttt tttatagaga gatagagtta tagaaaaagt ttttatagag À. 661 atttageaaa gattttttat cgagagatag agttatagea aaactttttt atagagagat 721 cgagttatag aaaaagtttt tatagagatt tagaaaagat ttttttatcg agagatagag 781 ttatagsaaa agttttttat cgagagatag agttatagsa aaactttttt atagagagat 841 cgagttatag aaaaactttt ttatagagag ctagagttat agaaaaactt ttttatagag 901 agatagagtt atagsaaaac ttttttatag agagatagag ttatagsaaa agtttttatc 961 gagatttaga aaagattttt tatcgagagc tagagttata gsaaaacttt tttatagaga 1021 gatcgagtta tagsaaaact tttttataga gatttagaaa agattttttt tatagagagc 1081 tagagttata gaaaaegttt ttatagagat ttagsaaegc tttttttatc gagagataga 1141 gttatagsaa aagtttttta tagagagatc gagttataga aaaacttttt tatagagaBc 1201 tagagttata gsaaaacttt tttatagaga gatagagtta tagsaaaact tttttataga 1261 gagatcgagt tatageaaaa cttttttatc gagagataga gttatagaaa aagtttttat 1321 cgagatttag aaaagatttt ttatagagag ctagagttat agaaaaactt ttttatagag 1381 agatagagtt atagaaaaac ttttttatag agatttagaa aagatttttt ttatagagag 1441 ctagagttat agsaaaactt tttatagaga gatagagtta tagaaaaact tttttataga 1501 gagatagagt tatagesaaa gtttttatcg agatttagsa aagatttttt atagagagot 1561 cgagttatag aaaaactttt ttatagagag ctagagttat ageaaaactt ttttatagag 1621 atttagaaaa gctttttttt atagagagat cgagttatag aaaaactttt tatagagagc 1681 tcgagttata gaaaaacttt tttatagaga getagagtta tagsaaaagt ttttategag 1741 atttogsaaa gattttttat cgagagatag agttatagsa aaactttttt atagagagat 1801 cgagttatag aaaaagtttt tatagagatt tagsaaagat tttttataga gagetagagt 1861 tatagsaaaa cttttttatc gagagataga gttatagsaa aegtttttat cgagatttag 1921 aaaagatttt tttatagaga gatagagtta tagaaaaagt tttttataga gagatagagt 1981 tatagsaaaa cttttttatc gagagataga gttatagaaa aactttttta tcgagagatc 2041 gagttataga aaaacttttt tatagagagc tcgagttata gsaaaacttt tttatcgaga 2101 gctagagtta tagaaaaagt ttttatagag atttagaaaa gcttttttat cgagagatcg 2161 agttatagaa aaactttttt atagagagct cgagttatag aaaaactttt ttatagagat 2221 ttagaaaagc ttttttttat cgagagatag agttatagaa aaacttttta tagagagatc 2281 gagttataga aaaacttttt tataaaqaqc tcqauttata aaaaaaotht ttatraaant 5641 ttagttttat teattcttat ttsagttatg aegaeggtta tataccaaaa cagcttttac 5701 ttttcgtsag aegatsatta cgttatesaa gattaagsaa ttttattttt actsaegtat 5761 catgsataat gacacgatat ttactttgtt ttattgtaaa astsaaaast atgttcgtgg 5821 ggagggggga aggaggagag ggsagacggg tatcatttta ttccatccaa tsaaccacag 5881 tgttatagga actagtgoac atcagtgtta taaaacaega agsataggtt tcaaactata 5941 cgcagttgac cctagtcacg tatccactat cagatgtggg agatcccact cggatcacag 6001 agtagatsag ttctcattat ccttccaaaa agtagatttt cactgtatag caggcagcgg 6061 cgoataggta tctggacata cagasttcca tattcctgat agctagagag acgsagcatc 6121 cgtagccagt gtgatcattt tcatasttca agggatcaga cgaggctgoc aegacattta 6181 tacaegactc ttgttatact ggacgsacgc ggagatttsa agacatggat gacgtatagt 6241 cgaggacgac ctcggtaata asttgattat attttcagtt ttsaaaastt astttatatg 6301 tactcastat cattatatag asttatttta tatattatga tataegttag gtagatgaeg 6361 ttcaastaat aaastatatg atgacgtttt tatgcgagtg ttacgttatt atsatagata 6421 atagsastsa aegttsaast aatsattsat tatattttca gttgttsast atattctagt 6481 tttataegag ttattcatat ataaaaasta tsaaaactsa atagtattta ttatgatgat 6541 acggaggtca tttsacaast ttacgagatg gagttaggtt gtacgggaac tsatsaccag 6601 ttggccgttc acagatttac agsaacgagt tttacatatt tcaaaaaaga acttttagtt 6661 aatttaggaa taagtgactt aastgatata aaaaacatat gagaggattc tesastattc 6721 tttccggsaa agagaacgga gatatteagt attsaegatc gtesatctsa acaastagtt 6781 ttagaaaact ccctaaaega tgacttgatt aaaaasttac acgacttgat ctatgatgsa 6841 tteagtacgg tagtagattc cgttacagta gagsatacog ttacattgat tatgtatgsa 6901 aaaggagatt actttgacag goatagagat tttagtacag tattttctaa aaacatasta 6961 tgagttcacc tgcttctata tttggaacaa ccagaaaegg gaggtgsaac ggttatatat 7021 atcgatsata ataegtcagt gsasttsaaa acagatcatc tatttgataa aactatagaa 7081 catgeaagta ttacagttga aagaggtaga aaatgagtgg cgttattcga tgtcttacta 7141 gaaaaaaagt tatcagagtc aacaaacgta ataggtagoa tageatactt aggtsaaaaa 7201 atsaatttat atgacagaga aastgatatt cagttgtgtt attgtgatat ggteatagea À . 7261 agsatgacag aegatsaaga atatagacta ggsatgatat ctgatagatc aggtagatgt . 7321 atsaaatatc atcatsaegg tagtattgtt agatacagta aagsagsata tggatatttc À. 7381 gatgatctat gtatatatsa catgsatgaa gtggatgesa tttggactgg tgatsageaa 7441 catattatat ggtatactat tgatsaaaaa acaggsaegt cttttatacc tatagatcat . 7501 gtactttacg aaaagttsaa agatatttat tcteaagagc atsaegasta caangatttg À. 7561 agagggtttt gtsatagoag aacggagtat atttgttgtt cggtatataa gtactatttc 7621 gacttacata caaaaacaga tttsatacac gaggtgatta attatataga ttatgatact À 7681 aagtcagtgg gtacacaega ctggtatact ctgactatag aegttesaca aactatcata 7741 ggtsatatgt cttaegeaga gttatttaat atagtaagag gteatatagc tattgsagsa 7801 gacastgaat atggatgtga ttsacattaa tggtsatact tttatsaaaa cteatctcaa À 7861 gtattgttta caagagactg aagtsatagt tttagosaaa tsatacattt actgttagtt À 7921 ctacastaga asttatgatg tsacatgagg tsaggatata tttattsata cgttacatct 7981 ttagsaegac tttgatagta gtatsatatt atacatatgc tatacttatt atacateaga 8041 aastttgtat tttatttagt gagatgatsa atcgtgttta aagtatacaa cggacgtcta 8101 tttccaaaaa atatgagagt gttaacggat taaaatatac atgaaastat ctattsaact 8161 ttatttctac gtatsacaaa caacagactg attttatata ttaegsataa ctattttatt 8221 aggtttttta tatagatgat atacagtgtt tttacgcgta tatacaaast aeggaaaast 8281 astsaaacag aastgattat ggosatatac gacagoastg catatattgt tsaaaaaaca 8341 ggtataggsa gtatattgtt acgagataac ggtactagga atactatgat tastattatt 8401 tacgatacta gtagtagtsa catgosaatg gtattacgag tttcagtact ttagosaggt 8461 atgtcatgat gagtggatag gatataatag taastgatac tactttacta tcastgaaac 8521 tsattggsat gatagosaaa aactatgcga tOttatOgat tattcattga tsaggttaga 8581 teacatagsa actateastt tagtgtagag atacggtsag ggtagttact ggatagacat 8641 aaatcaaast agsaaasttc cgggtattaa tttatcacta tattatgsac aaggagttea 8701 tgatatttgt ctattatttg acaegagtsa cattatagsa atgtattgta tatttcacga 8761 aagsacgata tgtgttaaag aagatagata cacocattgg tatacageat acatgagtta 8821 gatttactac ctatttttta tacaatagta ttttgtacgt tattgtaaac agesastccg 8881 tatagtttat atttttsatc aaagtaatsa cgastatatc gatgtcaegt ataaaegoag 8941 attctagata ttsaattatc aaegtaegtc atttgoattc catgagatga tactttgata 9001 ttttattata cagtagtata tacaaccact acaaagttsa acgsagtaaa attattgatt 9061 cgttgttatt atttcagoac agtagtactc gatatattag tttaastata atsacacgac 9121 ctttgaaaca tttttgtgat agatsataat acOttattat tacacteacc tgtatttctt 9181 ctastattta aggtgtgata acgatatatc acgggattsa aaggttatta gtagtagtat 9241 aacaacataa tastagcaca tatgtatatt tatatacatc tagagtacat aaaastaata 9301 tgttttgata aaaegtaaat caataagtgt ataaggtatt atttatttta atgaagaast 9361 aggacgtsat gtatsaatca gatttatatt cacgsaasta tttttcttag atgtatatgt 9421 tagttaastt acgtgattat attataegtt atatgattac tttsacatta tatagtsatt 9481 atatactaac cgatattaac acttcagtac aaagaggtat gacagoatat gagagatatt 9541 gtgattttag tatttagata tgtgsatata gttatatact aacgagactt tcctccaatt 9601 tacaaagatc taaggaaaaa aaatsaasta atactaccac gttcatattt tsagagttsa 9661 ctatttactc ggaggtatag gtatacatac asttctatat aatttagtta atagattttt 9721 acgagoatsa gtatacgtat aatgtatttg tttaagtsac tatcactgga atattcctsa 9781 aastagagga atttttgttt gtacgtcggc tactaggaac atgaaaggta cgttcgattt 9841 tacgatagga attttattta ttcagtctgt agtgoatast taggteacac tagatgattc 9901 agttcogtat tcatctactt ttatcacaga tttttgactg atattacata tcctcaaagt 9961 ttttgtatag gatatacata ctsattcacc tgacttgast agatcattac atcacatatg 10021 gattagagag tatttcaegt ctacgtcatc ttataattag aatttaggta astaaagsac 10081 tatttatttc aaagtcatat cttttttaga tattatttta ttgatattct tacogttatt 10141 gagagaatca actactccat ctatacatgt aactgsatca ggtatgatta tsaacatsac 10201 aastctataa tattagtatt ctaacatsac tacatgactt cttatatctt catcatgatt 10261 atagtaaaac gcaacgtatt gtatcatcat cgtatatatc atsacatatg tcacgttata 10321 ttttttgaaa ggatgtttag aagttaattc tgtatagsaa ggatatttcc atttagattt 10381 aaagtataat acgtttatga ttgacagtat tatatcatat gatagtgaaa tgatsaastc 10441 tttaataagt cetctcgtag atagttatac ccatttattt atagtttcag atatagtatc 10501 atatgtsaaa ctgactacat ttgagttgea tatatagtsa ctagagttta tesastatat 10561 ttttataggg tatcattatt ctattsacat astactatta tttatgagtt cgtcattgtc 10621 gtagtsatac tatacgteat attatgactt atcaggtata ggaacgtagt taccaastat 10681 tcatsataga tattttattt tatcactagt ctatttttta catcatatca tgatgttcat 10741 tagtatagta tataccactc taggggaaat acatatgtat tttccaggga catatagttc 10801 ttttaatsat cttactaagg aacacatagt caactastta tttsacaaac atatacttat À. 10861 atttccattt ctatgtsata tgtatatacg aagagtcaat aaaaacatta ttttactata À À. 10921 cctcatcttc aastgtagat tttattattg tteacaacat agacattagt gattcatata . 10981 tagtatttcc gtgatcatac tcatagatag cacttgtsaa agtttcastg tttttagttt À. 11041 cgcaegatgc tastatcttc tatatgaact tacattcatt aaastatttg aaegagggaa 11101 aastatattt atatttatat agagaacgtt tagoaCgtga tacgtcagsa cacagatsac . 11161 acatgatagc atsaagtsat tgatgtatgg attagtattt tgacaacata gtgttcattc À. 11221 tattatatcc cacttgttca aaasttttac cagcactgtc aaaatattct ttttgtatag :. 11281 ataacatagc asttagoaac atacastcat cagatagttt attatatcat tcacagacat À 11341 astatccaga tgcattctca tagtgsasta ttgatttatc tagttatsat atatcattat 11401 catsastagc ggatatattc atgtgacatc tagosactgt atsaaacttt catsaacaag À 11461 tatatacatc tatagattta gatagacagt ttatagattc ateactatat atattattsa 11521 atgagtttgc ggoatataca aaactagaag cagcggoast agasttttta ttattttgoa 11581 atagoatatc acatgattta aaaastgctt tacacgoaca ctcacatsac tgtacggacg 11641 caaaaegatt agoagagtga cttaccatgc cggaggattc ttatatttat ataggtggac 11701 caastagatt cttsaaaaag gacttacatt teattttatt ttatgoatct tatesastat 11761 tggttgcttt ttgttatact tctttgcgat ccatctatac tsactactat aacatcattt 11821 atatttacat attatacata tgagateatc tgtataaaaa tesatatctg ttatcgagta 11881 ctgtatttat ataggsaaaa atatccaata actgagtcga aggacatagt gtasttastt 11941 tatttaggga tatttctatg gastttagta tatagtatat acatgatatt acttttatat 12001 tctctatata ttttaaaatc tgacgtgtat agtatagtta ttacaggatt catagoagtt 12061 tagaatttaa astatccatt acageacatt agtsaaccat agattgsatt aegttttatt 12121 tcgtatatag ttttcagttc tttctcacag gtgtgtcata astgttatta geagtgoaga 12181 agsatttatc ttattcatat tsagttcaaa acattgtact tattttattc cgeacatacc 12241 ttttattata gtsattatta atattggtaa taggaacatc gtatccagaa catacgtatc 12301 acatatgttc gttattttat aaagoatgta catatagttg tttatatgtc tagtggasta 12361 catggtggat tacatactat tastaccata tactttatca acastttatc tagagtgtga 12421 caacagoaeg gtcattttat tattcatgta atattagata acaagesagt atatagatca 12481 tgacatatat tttacattat cgsatatatc gtatsagttc tsagtsaact cggoattsat 12541 gactatataa tgttggosag aaacatagsa cgggtattsa tatgesatgc agtcatatta 12601 acgagataat aaaasttaca ttatcaaact atcatccatc gattactata ttatttatac 12661 tttatsaast cggttsacca gtattattattsacttteat agcgtcattc aagatcaatt12721 tttttatatt atagttatta agtttactta atatattcaa tttacacttt astggsagta 12781 aacaccattc tgtatttaac gatgataast tacaactatt aacacgtacc gaggsacaca 12841 gcaactattt catatatatg cccatttata taatattatt catagtatsa cagtsastac 12901 gtsagttgat ttgagattat atsagattat ctagaaaggc gacaaaactg ttatggtata 12961 tgtctttaat atcttccaag atacatattt caaaaaggct tttatcacat atcactatag 13021 tagtcatgaa agctatttcg gatttacatt tcagagoaac ttctagtast ctactatttt 13081 ttgosatagc cgctatattc ctattaaaac cttatatatt aacagttata gatgatttaa 13141 attttgsast aattatataa ggtacaagat taeggatagg tatattgtat tcgtcaasta 13201 agttsatsaa atattccatg attgtataag ttacatgacc tatgttsata atctggttac 13261 agttagcacc tatatccatc astaacttaa gaatagtagg tctatagtsa ctsattattc 13321 ttacaagagg agtaatacog tatttgttaa catagttagg attagoacac tcatatsaca 13381 aaacattaca cgttttasta tatccagtac atatagatat tastagagac gtatsaccat 13441 cattagtatc tttatataca ttagatcagt atattatcaa tcgtcttatt atttttatat 13501 tgacagtttt agcggosata tgtsaeggag tgtaggsatc taegttaggt gtattaggat 13561 ttacaccttt atacaatsac tcaaccacat tttttatatt acatttagca gtttcattat 13621 atsaagaegt atatccatag ttattgacac cgtccatttc tgtatccatg astacastag 13681 attagttata ttctatgtsa tastaacgat tacatgtata teacatatac tatttatatt 13741 ttcttatgtt atataaaaaa gttatttatt tacatsatea gacttttcat atcagtattt 13801 tctagtattg agsatatata gtgttttatt ttagagtsat ctattaccca tacaeggact 13861 tcagsatatt aastatttat ctgttaaggg tattgcattt tgtagtttca tttttattgt 13921 tgaegatatt ttsatastac gaggoatggt gtatttatat gattttgagt tttactatcc 13981 tattatagga tattgcgaac gcatttttac cgtattgtag ttttagtgta tagatattat 14041 acagatttga tttatatatt atatagattt ccatgtgtat aagatattta ctattattcc 14101 acggatattc tcagsagtgg ttcacgccat ttctttsaca ggacattgoa catttcaggg 14161 tttsatsact aatactaaag acgtattaac ttttccatat tatatattag gattagttgt 14221 tttatacttt cttatattat aattgagttg ttgtttttac gtcaagsagg agatagtata 14281 tccatggtga gsatatagga gtatgoacag ctttgtagta atagtattat tattttaBcg 14341 cagttsaegt ttacatatsa gtggggtagt attattatat agagttatag cattgtgtaa 14401 ttcttttttc cgcagtgatt tatcatgatc cgggtaggsa ttgagosact ctatagattc 14461 attgattttg attataacca astccatatg agaaggatac cagtcagtag tsactattgt À. 14521 tttcattttt catggataat ataaaaatat tatsacasta agggagatct tattcatata

14581 ttttttataa gatatcatac ttsatcacta atggaagatc tgaccastct ttcastccat À 14641 tatcatttac attcagattt ttttcaaaeg cattttccat gacatcaaga gacttgtcca À. 14701 gagattagtg tatcagoaat catatttaga tggtatattc tattagttgc ctgtaastga 14761 agastcattc acaagatata caattteagc attttgatat ggoattgtca tagosattga . 14821 gacatsagtc tsatagggsa cgtatatcag aacataaagt agtttttatc attttatata À. 14881 cttattatat acaggsatat ttccastatt tcatttcatt gttagattct attatataga 14941 gatcatttat tatagattat tagttsatca ctttgtggta cttatattat gtgtttataa À 15001 ccattgttga tattatttgt ttagatattt ctattcatgt gtaggagttt aastcacaaa 15061 ctgsaagagg tgtatttatc catgatgesa cagsagtatc tgcacagaag tccaacaaaa 15121 cttttacgat atagagttca gatgcgttag ctgagaggsa tsaaggtgtt cttcagosaa À 15181 agtattgsac ttatacgeta gagacgtgtt ccaacagagt aagtaccata tatgoagaac 15241 cttccattac cgagtgatga agggaactsa atgsaagttc atattagaca tcaggtaaeg 15301 cacacatgga gagcasttca actactastt catsattgac agatattata goatgatgga 15361 tggtgtaaac agatcocata ctcattgeat taatcatggc tcaggoatat attageagat 15421 tacagatttc aagatttcca ttagaggatg cgtagtttat agggoastta aacatataga 15481 tatattatgc atcagagaca tsatatasta aegttttagt catatttaca tcattgagct 15541 tsacagoata ttccagggga gtaegacttt cgtggttttc ateattatca ggatcaacat 15601 tgsattccat tsacaggtta actatatcat astgtcttsa tatsacagat ctatgtaatg 15661 ctgtaggagt agactaggtg tacagatcag gatttgoacc ttagagtsac agsattatag 15721 ctatttcagt atttccattt tatacggagc agtgosaaag ggeacatcca tattcattea 15781 ccatattagg gtcagagtca ttgactttta aagatttsat aacatcagea acacagacag 15841 attagatagc ctcaastacc tccatgttgt ataatattgg tagtatcagt gtagatacac 15901 cggatgtacc aagcgatata aaastaatta aastttcaat ttatttaaca ttagtatgtt 15961 tatttcatsa tgtcattatt agtatttagt agttagoaag tgacatatta caactastaa 16021 gatcaaaast aaaactgatg atgtataatt tatacacata aegsaattat ttatsaastc 16081 ctcagacata gsaatastaa astgacatsa ccaattcatt tacastgttt atttattcat 16141 ttatttatag gtatatatta atsagttaaa tatttttaca agagtsaaca cgatttsata 16201 aastataata tastatsast atatttcaaa taatatsaaa tgtatatagt tagtsattgt 16261 cttttsattt ataacaaast aaastcteat agagtsatat ctttttagtt tcatatacat 16321 cattaggatt tacacattta actaggtttt caggttcata acttatatsa tatatatagt 16381 ctatataatt atcatsagta ggattsaaca tttattattt attgacattc ttacatttgt 16441 tggtataggt catgttggat ttcaaatatt cattatatac tsaaggtgac attgecaaac 16501 agaactatga cataggagac agtttttata catsaasttt accttcacag tataccatat 16561 teaggatttc atatattgta gtatattgag tacatccaga aacatattag gtatcaggat z 166Z1 gtagacatcc tatgsatata ttgastatta tacatgatgt cataaactta catttagtat 16681 cgtsatagaa agactttsat atcgattctg gagtaggtat agttccattt acatgoatga 16741 ataccatgat attagtastc ggagttactt cattsaegoa tgatttgatt tcactactta 16801 tttcgcgtag tataaccatt attgtaastt ttagtagtta tatattactc aaaegsastt 16861 accatttact agttaattta taaaacagag agtattsata attcacttat atattactca 16921 aaagaastta ctatggttca atgtatagac atatageagg aatsattsat tcaaastatt 16981 tatsaastag tattatacca tattcagtsa acatctttgt attatgttac tatgtattcc 17041 tttcattgtt cttttccgac gtaatgtact ggaasttatc tagcgtgtgt attattastc 17101 caatatatgc aatatggagt ttcaacatga ccgactacac tttagtttac ctttatactc 17161 gtgtatatgt aatactctac attttgtgta aaacacogag gtatCtagta tgacatsaca 17221 cctcacgtta ctataccggt tactatccat ctaggatagc cgtgtttact tcctacaaaa 17281 caegttattg ttgtttcatt tatatgcttt tatactacat aegttatatc ttatttttga 17341 atttaggtac atatttgata cgtttcatat tttccagaag cagtaegtag tacacaggta 17401 aagoacaaac tttgaggatc tggttttttg acagtsaaeg tagsagtact tccactsaca 17461 gttacttcat acatatattt atsaggacca ggsacatast tgsaegcgtt caacccgtsa 17521 ccgcatactt gttcttgagc taccatgata ttatcatagc ctctccaagt agatatagat 17581 atttagtatc catatttggt tatacattgc aattttacag ggatatcagg tsastattat 17641 tcacagtaga tattttttaa gataastgat attatsatag cgattgatat aaccatatag 17701 ttcattttca tattgattgt ttttatatca aacgatgsac aatatacgag gatgacatac 17761 tagatactat acttattcac ttttattsaa astatgttaa tattaaaaaa atcaaaaatt 17821 attccaacca catattatsa cgggatttat ctcagtattc caaaaatgat caegsastca 17881 geaccacgga aaggtcttga cgaggttatt tatcatcaca agatateata gatgatatat 17941 astatatact tagacocttg taacttacgg tgastatcac ttaggtagtg aastcagtat 18001 astttttatt ggcgactact ttttcacatt catgatattt cttgtattat actsattgag 18061 tatcttegat taacaccaca ccacacgatc tagoatccac ttttacttag ctatattcca 18121 tagttatagt catgtttatt atsaastcaa tcaaacctat acacacatca tatacagoat 18181 aegcgtatac tagaggoatt actateagtt ctateatgtg tatgtsactc tatgtattgt À . 18241 tgtsatagsa gatacatata tagagacatt cgtcatttat ggatgatatt ctaggsagat À. 18301 cgacgttata ttatttatat ggatagttac aatagoagat actatattat caggoattat À. 18361 gtatgtcast agttacatta astgtgttgt ttttcaggtt tcattttata actaccagtt 18421 tagtagagtg tatgtcaggg ggtagsatac aagtcaastt aactattaca tagttatgta . 18481 ctaccattgt ataggsatta cattgtatsa acgtagtcaa tsagastaga gaaastgagt À. 18541 atatatttcc gtacatgatt atatccagta atttttttac caagoactag tgattcaaca 18601 atagtgttag tgttatactt tatgtttttt tatastasta tcaggesatc gttttsagat À 18661 cttccataga taaattagat acasttactc tatgtatatc aggagatsaa agacaccatc 18721 tactsagatg atctttacta gtgtattcat tgatgataga tsatacagac tatatagaeg : . 18781 astttatttt ttccatgtat tttatatgtt ttttsatsaa acgacgesat attattatat À 18841 gtttsagatc tatcagtagt ataegtttta tagtgttagc cagatcatcc agtttatata 18901 atatcagsac atagtacaeg gatattttat tatcacaegt ataaastaca ttgtatttca 18961 tsatagacaa ttagttatat atttcgtatt ttastgattt ggtttattta tgattgttta 19021 cgeatatcat attacgtaca aacacttgtt tattcattat agsagsatag tttattacag 19081 aaaagtatag gtatatagoa gataggsata cagoaggatt atcatgagtt ttatgastgg 19141 tsatgggagt atgsaatata ttcataaaac acatatcagc tcagtgttat agsagtactc 19201 gagtacactc tttactatta ttgagtatag cgtatgttsa tgaggtattt ttatcatsat 19261 ctgtttgatt aacgtaggca ccattagata ateagtattc catattactt actttacact 19321 ctatagaaca astcattesa ggtgttatac cgtsattatc catttagtta acattagatc 19381 cgttattgat tastactttt atattacaga tattagsata catacaggat aastgtattg 19441 gtgttttacc gtatatattt cttacgttta cataggoacc tttattsata agtagtatag 19501 teagacttga ggtatttata gsaacagacg cgtgtatagg atacatatta caagoatagc 19561 acgatacgtt tatatcattt atatttttta atagttttat tgteattggc aasttcatta 19621 attagtatat acacatacaa agtatagesa taggtagata attaacaggc aaactaagta 19681 tgtatgagat astgctatea tacagtttac atattgattc tattagtata tagttacaac 19741 accttattag agatcagttc ttsaccagsa tattgsatsa ttttacacag tgtttactag 19801 acattatagc gtattttaac atagsatata tatatcatat atccggatat gcaccatgat 19861 ttastaatag cattaccagg gtsaegtttt cttgttatac agoatgatat agtgoagtat 19921 gagagttttc acatattgta gaattaatat caataccaga atcaaggsat agtttcacca 19981 ttttaggget attggtttta acagattata gaasstastc ttatsacgat gtatcogtgt 20041 ccgatsatsa gttattagat ataaagtgtt tcaccagttc tatatttact tctatsatag 20101 cacactteat agtsattatt ctcatataat ataaactggg atgtttagtt tattcacata 20161 gsatttggoa tagaggtata gtactaaaat atgsatatcc tatagagtsa caggttttea 20221 tgosatacga accacccttg taaaastata ataegtaaga tatacatacc attttcaagt 20281 ctgctccgtg ttttatcaga agttttacta ttttggtgta tttttatgta ttattsaeeg 20341 ttastagaeg tattattatt ttaetaggtt ttacgggctt gttateatta tatsaeatea 20401 ttetaeatee egatsatatc atagctatgt tgatgggatg tgtttttatt gtttateate 20461 cgttgatsac ggcattgttg tetagtagca tttatactat ttatatgtet gaatgtteta 20521 tagagatgtg taaeggsagt agtctattgc tgtcgtacat gtttattaea tatttatatg 20581 atectatcaa ttatcgsagt ctgtatacat tattttettt taegatgtta tgtsatgata 20641 acaaaegate eatagtgatg tatttgtacg ttaacgteat tattttttet tgagttatge 20701 aaagataaca gtgattttta atatatgast teatttattt tagsaetsag etattatsat 20761 astatatttt aagastaaat taettattat ateataaaae acasttatea ttaetttatt 20B21 tatatgttea tttttgttta taaggatttt gsateaaega cgteataeae gtattsatsa 20881 cactcttgac gatcatatgt gtaatttttt goattatgtt tgtsaggoat tttcagttta 20941 tatgagatat atatttgosa attgatgttt taeatttagt taaatastaa astattgtat 21001 ecttgttatt ttcatsagoa ttatatatat gtaaaeetat astatttagg taetttatsa 21061 aasttttgea aeatgtattt eteattttte ttattttata tgteattttt cattttatag 21121 agtatteeat ttttatteat aaaaaaeatt tgtagegtgg gtgatggtsa gtatateaeg 21181 agttaettat agatatattt astatattat egaeggaagg aegsagatee atggtatgtg 21241 ttatgatgtt tatgteeata aagggtsatg ateastacta tastgttttt acgatcacta 21301 aaatatsaat ataegaatat agatattgat ataaaagagt attggatsaa tacggttatt 21361 catataaaga tsatatgact gttaetaast etggtgttat agsagagtta gsaaaeteat 21421 ataaastaae tsattgatge astaeaetae tttgacasta goactgsaga cttatacaaa 21481 atsagegata egtataaaat aagatttata tatgsatagt agatttatgg tsaaeoggta 21541 astacgsatc catctactta tgsaatacgc ggaaaastat ttcatagata aeggtattta 21601 tsacgattat accaegtcat aaaaatatat actatagaga gaacgsatat tattttttta 21661 taeaetaste gttatagatt gtsatgtage tatagetttc gtcagaetga aggteataet 21721 ettgtttaet taaaactatt ttgsatagtt gatagagtte atsaetagaa agosastcac 21781 gctttttgga atattatagt tatttccaat ctgtagaaat agattcaaga gaatcacatt À ,. 21841 gttttatast atagttsata atactttatt tatcaggtaa tttsaastag tatttgatta 21901 ccatacaata cgagtaatac ggttatgoat cttcattact ttcatcasta tattatattt À . 21961 catagoattt agagtgttct ttactagata ttttcattsa tttgtcaast agttatttat 22021 cgttaggoaa gtagttgtag ttttcgttac tatctatact agaccaegat atatagttaa 22081 ttgtattttt ctctagatac gatactgtat attatatatt aastttagsa acgatsaeat À. . 22141 eetgaaaaga agsaastaea ataggatgtt etatgetatg tattttgttg tttatatgag À 22201 ttastagaca ttttcaettt etatttatca aastaceage acgoacaagt tttttattac À 22261 agggaggtgc tatatatata aetteaeast aaeataatgt attattgttt tagaggtagt 22321 atsasttsat agaaaeatcc aagtattata ttgtatatae tataeatttt tatgatttta 22381 attteatagt gacgtcaegt aacgataegt aegttacacc ggatteaaet atagttgttt À 22441 eatgatatae ggatttatea aaeagaaeat cggatgsast atatsatgaa tttattcatt . 22501 tsagatagsa ttttgttttt catcattctg tagatttatg aagtagtsat astatgtaca . 22561 tgoatagtgt attttttgat ttttttttac agggtttatt atttgttttt tttsastagt 22621 ccactacacc gtsaacaaca aaagttacat tgttttatac gagtaettag eteaetatgt 22681 attttaactg cgataetata agattataga gtttagtagt tsagtettta eagagggatt 22741 eatsaaeast ttgattagat ttacaatgtt ctaagtcgag tatetegtat eeagtatgtt 22801 catatsaast tettgaetag etsaagteat agteeatata gttagtttat atttatteta 22861 ttaaeasttt ettgsastea gaaaagtsat catatgsaaa tatatgoatt tttggsatac 22921 catatattat atacgtgsat gaeatattta eaaaaaasta tattatttat gttttatatg 22981 astatatata agtaatesat gsasttaaeg ttateaacta ttatagtata caaaastgga 23041 taeagattae gggacggtte ataeaeagea gtatgtesag ggsastaett tgattatatt 23101 astatatttt atatagttta tagtaggatt teatggtsat tgtaeggtta tatggtttae 23161 gggatataga tggesaaast etgttaegac tatatggttt ettsatetgg eaetagatga 23221 taeattgttt gtsatattta tteatttaga gattacttat atattsatgg gaeaetaetg 23281 gacgtttggt ttattagtgt gtagastagg atatattatg tttsatacag goatgtaege 23341 tagtatattt ttccttacat ttataagoat agaeagatat tgtetagoat ttagtaggga 23401 tatatgosae aastataggt atagsattea catsatggtt atgatsatca ttagttggat 23461 astatatata ctgctatata cteattacat gtattttaaa aacactsaeg aaaastacag 23521 tsataacaga gactgattgg aegattacca ttaggatsat aatacttatt tactgcgtag 23581 tgtagtattt tgtatatagt tagtastgag atatttagta cactcagtag teatgttatt 23641 ctgttattgc ttattsettt teaaaeaeag tttattteta tataagggae agaettseae 23701 catagtgatt atgataactt catttatggt tttatggacg cattacaata tattatattt 23761 tatagatgtt ataggtagtc attactacaa cgcagatacg atsatagatg ctgatcatat 23821 atctatatct ttgatatttt taagtagttc aatcastcoc atgatttaca tgatggttgg 23881 tagatatgta tattttgaaa attattatat gagagsatag ctaaasttaa tattatatga 23941 ageaegagac astcaaacaa atcatgaaaa cgagattsaa atggaaaata ttasttaata 24001 aaastaatat aagtatatca tastttttat agttcattat ttgatsaaaa acaacatata 24061 attgatatta tttctsaagg cagoatatgc agatatggtt ctgtagtcag tacagcactt 24121 tatagtagag tatatctagt tagtgacatg catatgtttt tatcagatag ttatttgtac 24181 acgttagatg tttgttttag tacctttast tttggatgat tcacaastat ggctattacg 24241 ttatastatt tttatattac aaastcgsat aaactatatc cactsactag tttttgOtta 24301 atcagttagt ttagttcatt ttcacattOt aacattatat ttttataata ttcasttcag 24361 ttsatgaaag acaegattat tatcactsat ggatctttta ttsactattt attattatta 24421 atcataatsa ttaggtgaga tattaatgtt cttatagttt ttttacaegg acacgcttat 24481 tatataggag ttattccatt tgtattaacg ctattgatat cagatcataa atatastaeg 24541 agttttattt tcttatattt acaacacgat gctsaagtgt gtsatatagt attcccgtca 24601 gagtttttag cgtttacatc cgatcatttt tgteataata aattaaacac gttatcagtt 24661 tggtaaatga tagacgtttg teacggtatg ttacagtaaa ggtagcgatt gtttatattc 24721 gatcatagac cgaggatgag tgatacastt tcaggattat ttgtttttat agattcatac 24781 agtsactcag ataagtastc ttatgatsat gcaatatatt ttattcagtg cattsasttc 24841 tttsactagt ctatactgoa atagtacatg gcteaaggta atgttatttt atccatgtta 24901 accatsaact ctaeggtata aaattttata agttcatata atataatttt attatttatc 24961 ttaatagagt aatacaaagg agatacagag tgttagtata atactttagg atcgoatcat 25021 atatccagta agtatattac agattccaac ctttatgatt ctacggagta gtgtsaegag 25081 gtggthcctt cggtacataa tatatctctg tataacgata atatatttag tacttatata 25141 ttgtastgag ttactataca tctcagosat atttttattc tttctatatt atcagtsatt 25201 gatttgtttt ctaccastaa tttgattsat gataagttac ctttattsac cgoateatat 25261 aaggoagtat gtcagtagag atcaggtata tctsatatsa tattattatt tattagteac 25321 gsacatgatt ctsatgttag tttgtcatat atcatatcat gaccaggata tggaccgata 25381 ggttataaeg acagtesata atatatsatt tatatataac cagtatttat agaegttsat 25441 aggggtgttt ctcatttgta acaaacatat acagsagoac cgtsagsaac castattttt 25501 gacatagtaa gatatttgtt tatsacagat attattagag gaggtacttt acaagaggac À .. 25561 atttttgatc cgttactaag aagsasttca gctactttat gggatttcat acttacogac À 25621 ctacatsata tagtgaggtt tttactacat ggtttattsa gatatatagg tttgteagaa À . 25681 agtaatttcc ttattatatc tacatcatct tcatatatag cgagtttsaa cgcgcttttt 25741 cttatatagg ccattatgtg tggtatsatt agactatgoa catsasttta cgctatatat À. 25801 tttcastsat tgttagttsa atatagttat tcattcaact astagaacaa gatgtggatc À 25861 tccacacatc taaatagtat tattcatcca acaattcaga cgatattcta tcaggaacta 25921 tatcattact ctttttattc tttatsagtt tttcacatat tttagacatg ttcatgagat À 25981 tttcatgaga ttatatacat tagagatttt ttattaaacc ggacggataa tacattttat 26041 cattaaacag ttttatsatt aacattatct gtastattat tatagagttc agcttttagt . . 26101 tgtagtsaga cattagatta gtsaaaggag tatttcattg gttatcastt atatttatgt À. À 26161 cagagccgta catsaaaagt astttsactc tattgtagtt atgoattgat tggsatagag .'. 26221 gagttgttcc attagsacat ttgatattcg gatatgatcc attatccast aatagttata À. 26281 atagagagta gatgtattca tctatagacg ctaegtgtea cggcgteaca coagctttat 26341 cgactatatt aggataggat ccagattata ttagttcatt agatatatta aagtttcagg 26401 agactacagc cgtatggagt actttggtgc ctatagsaga agacgatgsa gsatttggat 26461 cagagacgat atatsatagt atacttacta attatatatt aegagtacta acggoacatg 26521 ctsaaggagt agttccatsa tagttttata tatttatatc cgctcagttt ttsattsast 26581 gtattaccat atttsatcag ttcatgtaat cacaggoata gtgtsatgag gtattacata 26641 tatagtattt gsasttsata tctatcactt tagacaacag tatatccatg atctgsattt 26701 cttatatttg catgataggt tccattagag atatagttsa goatttacta atttcatagt 26761 ctttacasta atccattatc attatcatsa gttcaactat ttgsastgea tsactagttt 26821 ttgatttatt caatatattg ataacttata gosattatgt atatgtattt gagoaccast 26881 tatagagttc gatsastgat gsattaggag goatagttaa agtatgsagt gaggtsatac 26941 cgtgtgtatc tatagataca ggatatacat cgttattcag taatagtatt actgactata 27001 tatttattag ttcaatagac ttatgaagga gsatatttaa tatgtaagtt gtaggtatta 27061 gatatataca gttatatatt agtttataca gtatactatc tattccagtt gtatatatag 27121 ttattttagt atagtccatt atacaggtaa atastsattt aegtttsata tagteattga 27181 ataagatata aaasttggtt atatttattt gttsactgsa tcasttatag attttsastc 27241 tttattatat aacatttcca ttatcatata ttttacgtta ataggtactg astttatcat 27301 acttatatta ttactgtatt ctatagoatc gtgaatcagt ttatatagta tacttgsaga 27361 tastttagtt ttttgsatgt attttttata tatactsata caagsagata atttatagac 27421 cttggggtgg ttcaagastc tsattagaat attattgtta ttatcagaat gsagaaatat 27481 cgatagagaa tataggtgat tcaactttat attcattata ctttttsatt catcatcaca 27541 attttttata ataactttaa atatatcatt ttggtatata cattatatat ttgatttgsa 27601 tccatccast aaaastagat tactatcttt ttctaastat astactatat tagagattat 27661 gattgtagat attttatagg atatgtsatt astacaggat agaggagtgt gacateattt 27721 gttaatagag tgtacatcga cgttgtaaga catgagtast tataegatat ctagtctatt 27781 cgatsagata gcgacatgga gaggtgtatt ttcattgctt tcatttttca tattagggtt 27841 agatcagtac cgtsatagta acttagoaaa ttttatttgc ataaacgtsa tsatggatat 27901 gtatsaagga gtgtaacctt ctatgttata tatatttact tcagacccat gattcagsat 27961 ttcagaaagt atatttatgt ctttggtttc tsaagattta tgtatcaaag gatttatact 28021 ttttaggaga gtgtttgagc cgtacattag gagtsagttt attsaastat tgttcatgtt j 28081 acatacagat atattaegaa cggtatatat agtatagtta tgtatattta cgtttgcacc I 28141 tttttatata agtastgtag tagagattat atcgttcatc gatacagcgt astgtsaagg I 28201 agtgactaga cacgeatatg ttatattagg atctgagtca tsatatagta atagtttsag I 28261 tatgtcgtgt tttccagcac tnacacaata atgtsaegsa gtcatttata agtcatattg 28321 ttagtttacg ggtacgccat attttatcaa taaacgtesa atagsastat cacagttatg I 28381 tttcacagac gtasttsast aatgattatt atatccttcc ggtattgtta aegsagagtt I 28441 attttccaaa agaagcttsa tsagtggata atttgtgoat tttatagcat astatatagg j 28501 ggttttsaaa tgactatttt gastatttag acttacttta tactttatca gtattttgsa I 28561 astatatata ggtattttat tatatatagc atcacaatag tttatgasta aegtattagg 28621 atcagagact ctttccaaaa gatatttagt astatttgta ttaegtttac acaaagatag 28681 atataaagga ctattacata aatatacttg ttagatatag gcacagtgat ctactastag 28741 ttttaccatt tctacattac ctaegttaat agacttatga aggggaggag atttacattt I 28801 atttatatat gagaegttat ctagtaaaaa tttaacasta tatatatagg asttacttac 28861 cgatsastat aegggtgtag ataacgeatt tttgttagaa astgtatact tattsaggat 28921 aatatgtttt acagagttta astatatagt tataatagtt ctatgtaast cttttateag 28981 tttttcattg cccatgttat atastcatta tttactataa tateatatgt ggtagtatga 29041 acgttsatsa atataagttt tcatattttt tgttatatta cctatattga tsaaaaetca 29101 ctagtaccaa ccagttactt tsatttttga acacatgsat gattccgcca attagatgsa I 29161 aegattttta ttgtcttcat catcagagat caegtagact atggtaacgt gaggacacca j À .. 29221 tacaggatat gatsacacag agaegsaast ttatataggt gtaggoacaa cgttsastag I À 29281 tacgtttatc aaggatttca catcatcaga tgactccagc ttcataacca ctgatctacc À . 29341 gttagatcat aettatttag acgoacgact ttgaggesag caastcactt ccttgoaegt 29401 gaaggsaegc gatgtcaast ctatattttt tgttsactat ttesatattt tgaagtttga 29461 ttattggtat ttgtttgata ttcacaaegt tacgtgggga ggtatatcac atcacgtcat À .. 29521 gtatttgact gctatgattt ccaggtctga tattcacttt tatsatataa tatagtagaa 29581 tgsastggag gcocasttac agtastcaca aggaacttat acttatsatc ccattsatat À 29641 agoatcattt ttattttgat tttattttac cacgattttc tateactcat tatgtatagt 29701 agtagacatt ttggttagag taccastggc tatccastsa taaaaegatt aaastttcac . . 29761 ttattttgea caegatgata tsastsatat astttttaag tagttageat atatattttt À 29821 attastttta aagtsatata cggeaaaaeg tatcatttat atttaccagt ttgatgtttt 8., 29881 taatgtatag astgtttttg tatatgtctt ctgagtaggt gacatatsat tgatatattt . 29941 ttgattatag ctgtateaga tagaastatg cgtttgtsaa tagtatagat atagtatgag ' 30001 aacatcaggt tatatccast atatttatgt ttagttatat acagtsatat atgtsatact j 30061 ccattsagta ttatttatag aagttattat cttatttagc atasttcttt attagtcatc 30121 ttttatacaa tsatatatat aacttcatea ggtaggttag tgatggtact cgtcaegata 30181 ttsacaacac gatatsattg ttattttcta tatesaccaa tatttatata ctgatatata 30241 atatcacagt atatatgaaa ttagttttta tteactcata cgagtaatag ttatatacat 30301 cttgatagag tgttatgatc atattgtttt ccagatttta tsaastcaaa taccgtcast 30361 ttatatccag ctatgageat tttcatattt ctastttatt cctcgoataa atttttatsa 30421 tagttsaacc ggtagatact attagtaaag tattagttta ttttgsatcc tggtgttsat 30481 ttaactttat

* caegeatatg agatatcata acagaegatg atatsagatc cttgacggtc 30541 atggatagag astttccatg goagtaacaa taccatgtta gaggtatgtg attgagtttt 30601 atattcaaga agsaaggatt agagactata tggagtagoa tttttattat aaaggggtcc 30661 gttatgttta cactagatag aagsatggta taccattata tacattttga atccactaga 30721 gatcagttat ctagosatag tgatacgatg tttatatttt tgtatsaaac agoattatgt 30781 agtacagtac gtcagttata atcagatatc tagagatttg gagsatattg gagteaastc 30841 tttaccatat tttcatagtt atatgttaca gatatctgsa tagggatatt acagttttag 30901 ttagtaatat tttgatcagc acaggaatat agtaacagtt ttgosatatc agtatttttt 30961 tgttgsatag ctsastgtag aggagtatta cgtsaataac atatggtatt gttsacgtag 31021 gctcacgagt acaatagtat acttacasta tatttgttac ctatatatac agosaagtgc 31081 aetacagaat aacatgttsa ttattattca tagtattcat tttcattsac attcacocag...DTD: 31141 tattccagta atatttttat gatatctatt ctttagsact ttatagacat tcttagtacc 31201 cgtattcatt catatttcgt attacattcc attastcttc ttacteagtt tatactatsa 31261 ggttgtactg tagattattc atgaggtgta tcatcatata aaaacatagt tgtastagtc 31321 aaataacatt ctatgtaaaa actsattast agattttcat ttttcaasta atatacacgt 31381 tatggaaata gccacataac tgaaastsaa atacttaagt atatattata ggatsacast 31441 gtatatgaat astattacga gtaaaatgsa tcaegatagt tatggatatt ttcaattaca 31501 tatgagcgat tttacacgtg tgtagatatc-gattgtattt acactagtat ttttggtagg 31561 tataataggt aatgctgtta tcatttggtt tataggattc aaatggacaa aaactatttc 31621 taegctatta tttatcaacc tagatttagc agactagtta tttttsatat tcattccagt 31681 atatactgtt tatgtattat ctsactttca ttggtatatc ggagsattat tatgtaggOt 31741 tagttatttc ttatttacta cteatatgta cgacagtatg tttttactta cgtttatatc 31801 tatagataaa tacttsacac tsaccagtca cagtttagtg tatesatacc gesastatag 31861 aaactactac gtgtgtatag gtgatatttg gtgtatttat atagctttag gtgttccaac 31921 tttatattat aagagggtta tattatcatc atatagsaac gagacacggt gtattagtta 31981 ttacggagat gatsaacaca cggatattac tatttataga attattgtgt gtattagatt 32041 tattatagga tacgtgtttc caatgacagt aatattgcta tattatgoat tsatagtata 32101 taaggtaaaa ttcatsasta aaccacagsa tagsagtttc atgatsacaa cggoatatat 32161 atttgtattt ctagattgtt ggacacatca tcatgtatta astattatat cgttgtatgg 32221 attaaaatag acatatatgt atsattatat aaaagsatat attccgttag tsastgatat 32281 tgagtttgtt tatagagata tsaatcctat tatatatata tttgttatta ggttsaegag 32341 tacttaegat tcagatacca tggatgaact aagaagtgag ttattagatg aagsaactac 32401 gtatacagsa gattgtagag atatatatag atagatttaa tttttgteaa cateaaaaaa 32461 agtatatagt atcaaaaaac taccatggaa gaaastattt tagtesaaac ctttgaegsa 32521 ttatacaaaa atagattagt agatgagatc tatcataaeg ataaactcat taegtttsat 32581 aaaaagaagg gtsaeggaaa caacttgtgt tattatatsa ttgsatacat teatcocatt 32641 tatgattatt gttattatgt ggataaagtt gtatatatsa ctsaeggagt tatgtatgat 32701 actttsaact atatgggaaa acatgtagsa aatagtgagc tagttcatat tastsastta 32761 ctataggatt cagaaatatt atatatggga gtsaaegata aagatatatc tactsaacat À. 32821 tacgsatata aatataaggt atatactsac caegataaaa aaagggactc gtcattagtt À .. 32881 astatastta aegatgatag tttgttagaa aaattagatt attttattga aggttacggt 32941 gattggsaga ttaccactat aagacacagg cagtttcata ataegttttg tesatacagg À . 33001 atatatsast actacttttc attgtastgt ttattatatt tttatagtag atgaegoata 33061 gtgsatcatt atcataaact tagtttagac tsactataca agatagattc aaacagattg . 33121 attagctagt atagsagsat castcatctc tatatgatcc tgaaatttat tatagcatta À. 33181 tgattataga atttatatgt tagatagtga ttagtagtga tattgtagtt tagtesatcc 33241 tsatagatta ttaegtttat ctttsactat atsatsasta tatgtttatt ctatsattsa À 33301 gcctatggat tatgatcata ttacatagta ttatatacta ctataggact ttatttagta 33361 tsagtatagt ctsacaactg ttacatcaga atgtatsata aaasteatac tsatggagtg 33421 ttcacgaggg tsaatsaatt taggacatag ttacatatat atsatsaaaa ttttattsat 33481 tttttattat tgttttttac agsatgttta astatageat gtataccaac gagatttttc À'.. 33541 actatgtttt agtagtsact agagtattat atagoatgta tgtggatatt ttctggtata À. 33601 tacastaatt catsattata taaagtatca aggttatttt atsaaastat tsateatggt 33661 tttsaagatc tagtcaaaga ttcaaacata tsattaggag caggacatta actesaacag 33721 tattacattt ttgtatttta tagttttgta caatatsata gttaaegact atagatgtag 33781 cgttttatat astatccatc atttcatttt cgttatatac tttgacagtt tatttsacat 33841 ggacattttt teaccatatt ttaagatsat caggagsata ttttttagat ttatagtagg 33901 cacttatagc accatggoag cattgagesa ctatttcacc tttagtcatt tttsastcat 33961 ctatastsac gsataccatt tttsacatat ctatgtsaga agagttatca aaaacattag 34021 ccattattag cacastatga taatatgtat tatttattta tgttttcagt atttacttaa 34081 tacaagttac ataaastata tcattatttt tacaggtaca tatactacat gtsagttttt 34141 aagtsagata cattagaaga tgttttgtaa acattaegat agsaactcat actagttact 34201 gtttatatat cttttattat tactatatga agactgsata ttttcatcac atsacttacg 34261 geagttatat totatataga acacgattag ttatsatagg tatagatatt gggtactaca 34321 astgactatg ttttsatatt agagtaacaa tcatttsagg aagastattt atccttacag 34381 tatgttagta taacgsasta atcagaeggt atataaactt tgttattata acagattgac 34441 atagatatta accastcact atatattata cogttgetgt tgatatagea tacagggact 34501 accataacgt taacgacatg atgtttttgt acatattaga taagaataga tgacataast 34561 acttcacata tatttttgaa attaegatac ataggtacag tatttgtatc caataggott 34621 tgesagtcag ttgacattgc ggggtasega tatccataeg taacatattt ttgagtacta 34681 tagtatatac atggttcttt atastacata actatcatat catgsagata goaggtattg 34741 ttatatatat ttgtactatt atatgtsata tagatactsa aagaegtcca aaggggsagt 34801 ctatttacat tactgtaggc agtsaegtaa ttatcatttt taataataca atgatggtgg 34861 cgattgagta gaacagaggg tttaccaaac ggtagattat atatgtaaga tgatgsaegt 34921 gttctggaac tgtattattt atttcettta gsagagaatc tgtatatgtt cttacaagta 34981 caacctttca gatgatatcc aacatacgag tgtatatcgc actcagattc tattgttatt 35041 atatctagag aagaaaegtg agtatatata ctatttataa gsatattatt caaagatcct 35101 acagtaccgt tgttgttagc gggatttatg cctsatattt cacacatcat attatagagt 35161 tcgatgttat cgsagatcgg gactcttaca tcatagagea aegcaggtcc atsacatsag 35221 aatacagcgg tcatatcttg gaaactatta tcagatcagt ggastccacc cgatagatgt 35281 tttsagttgc cgttttcatc ggttgactgc catcattctt ctagatatac tcacagtatc 35341 tcogttatga accctgatcc gtastgoaat cttttaggta gactgatcat ataacttacg 35401 atgsaaggtt gatcgtccat cacacaacta gtagsagata tsattcagtc atastagsat 35461 astattatat ggtttaastt ttgaggattt attactggag tagctcatgg ttttatsact 35521 acgtcattat ttgttatgta atatttcaga tttactatat ttttgggatc tacattagac 35581 ataccatgat ccgatactag tattaggtta gcgoatcata ttaattgcaa atattttsaa 35641 cctttcatca gtsaagagat tgatttgtca actttttcta aagcttttcc tactatttca 35701 tcatatgtac cgtattcata cacageagac cagggttctt caaggtatag cgoatagsag 35761 tagggtctat atcaegtatc catttttsac cacatcasta cggtatttat tatttattca 35821teaggsacag atttattata gattatatac atggtagggc gttttatagg aacaactttg 35881 tcagatcatg gccaaaagaa ggttgatgat tteaatcagt tcttcatgat agtagtccat 35941 atgggttcac ctccaaacca ttatacttat tcagtttatt ccgaegatat cgtsaactag 36001 atataggttc cactatatat gasttcatta tcagttatac cgtgagatat gggatacast 36061 ccggtsacta tactgtacaa gtttgggsat gtattagtag gatatacggg catcataggt 36121 gcagtsactc cgtgttccat taastatttt atogtaggea tatacttctc ccatttatta 36181 agatastcat atataaatcc attcatagat attagLatga gaggaggcat ttcaaattca 36241 ggaggacagg ttacatggaa tgatatacaa ccacatsacc tagastatat atatcagast 36301 aacaaacaca aaggtatcat tattacggat attgoagaga tagtagatag tgeatacast 36361 aagatatatctagtttcaca cttacgattt tttattggta tagtgtaaaa tatatccacc 36421 tttttttatt tgtagatast agsactatta tattcatagc ttatgoattc tttagattat 36481 tcttttacag gatacaatOt atsattatca ctgtgtatag acatatcttc ataggactga 36541 tatccatgat ccatagtggt actatttttc atagacattc gtataaacta attacttsat 36601 ccatcatttt tattatatat tattgtttga aegsaaaaaa tacgagataa astsacaatt 36661 attatacttg atacgagttt gsattattat ttttcaacaa tatcacgttt tacttcatgt 36721 catgatattt asttcatcat tatttatata ggtsaagata tgatcattsa tttcattagg 36781 teaattgttc caagaggatg tattactgtc attatataga astsaatatt ctsatacttt 36841 acttgattta ttsagaegta cgtgtattga catsaaegta tatataaaat ctgtatataa 36901 astattaaac acggtsagtt ttttatcaaa atttactata astatattat cattatttat 36961 gcatattagt astaaatcaa cattattatt aacgsataaa tcaaaaegtg taaatataga 37021 gtttatactt acatgtttca ttttatcast atattttaaa caatgtatcg ctataegttg 37081 taatatttta ttatctttaa ctagtttatt attatggtag astcatttag ttttattact 37141 catacaagta gaatsatata atataateac gtgtgacact astaatgata ttatttagta 37201 gttattacaa ctcatggaga tatatsaagg agttsacact gtattttatt cttagttatc 37261 tcttatatta acatatgott tatsacgtsa tagttttttt atgatatata tactagagtt 37321 ataasttact gatttatgta atggtgtsaa tccatcatta ttagtsatat tagtattagc 37381 acagtgsaat agtsatatat caactgttat gaggttatcg ttttttacag ctsastgaag 37441 agatgtattt ccacatgtea gactaegttg atttatgatc gatcagttat ttsatagtsa 37501 ttataccast tggtggatat tsastataga tgatatcatt aaaggtgtea gattatatat 37561 tatagtttcc tgaaegttsa tatcaacgcc ttttttaaca agatatctta caacatatat 37621 atsattaegt ttagtagata ctsatagtsa actgtttata tcaagtatat attttggaca 37681 tesagttact attccagtsa tgagtsatsa ctatattaga aaaggcatag ttttagttat 37741 atsatcaaaa ttatsaaact ttaaaatcaa tttagatttt tattaaacta catgtttata 37801 acacaacatt cgtactcaat gactgtttat tttagtsatt tsaacagata tccattcata 37861 gtacaggcgt atccacatcc tatatgacgt tgagtaggac tcatatteat atcacatata 37921 catacacatc cttttttatc gtsaagtgsa.acaatccatt tagsatgatc atsateatta 37981 atsaaegatg ttccatttac gtttatagat tttatgttat gtacatggta ttttgacgag 38041 caattggtta tcatactctc tcatatacgt tgacatgttt ctgatagtag gtcagattcc 38101 aaegtaggac ctatccatgc actcattata tcatggagaa aatattttga cttagoaaat 38161 gttaaaaact tttctcattt tatagattcc atccacatag aaacattttt atataaagtc 38221 gtatagtttt tatagttaca tagatggtat agattattca gattattatt tgttactgaa 38281 cagttataca cgtttgggtt attaacaggt agtgtattgt ctaaggacgt aagacatcat 38341 ttgtastcca agtteataca tsacatagat tgacagtata catsaccaga gtsaggatea 38401 ttgtatccca acacaggaga aggtggaast ctaggtacag astgtatcaa ccaaastcat 38461 gttacgatat cactattcca tgacataaca catttagtat gacatacatt cgatgsatsa 38521 tttttgettc ctgggatgac atcattataa aaastgtatt ctatatattt actatcatat 38581 aggtcatsaa taggatatag tgttttccat attatactgt atatagagtt tataggtact 38641 ttacatcgtt tccatttagg attattacta tatatgtata astattcatt acatttagtg 38701 cctasttttt ggagcttagg gagcttgtat acgaaatacc agtatactac ttagacttat 38761 tcatttacac astttacttt acatttatca tattcgttaa agtttgsacc gatggsattc 38821 agtatcttag agatatttga gatatatata ttattacaga tatsatatgt astacatatg 38881 catacggaca atgtsattgc cgtaggtgat atcattttat tgtatttatt atacttatta 38941 tacttatata tatttcatta atsaacaact tgtatttata gtattatata gtgatatatt 39001 tctactataa acatataaag tsatasttga aaggtagtag tattagttac gtactateaa 39061 aagtatatca tatggatttt attccctaac aactagastt agtttteata ttattgtatt 39121 ttggsactaa caagataata ggastagtcg ctaccatagc aatsastatt acgaccatta 39181 ttsaaacata tggatatatg aatttattaa tttatttttt tataatttat aaasttagta 39241 ccatcttast attaatttaa ttatatcacc atattctsat attgtattat ttttatgtta 39301 tttattatat cattgtgttt gtatattatt cttsatttat astsacatga tcgttsagat 39361 ataatccast ctagtaaccg aacogtattc tatteatgca tatactsata tatctsastt 39421 gcatgtatca caagattcta cgactttcat tattsacgtg tactatctat astcaatsaa 39481 ttgagoataa agttctgtat agtatcccac tatcastatc atatatttat ctcatataca 39541 gsaatggoaa agtatagatt tgagsaattg atctttasta cgatgtttsa gsataggtag 39601 tatcatgcat atgataccta tttgttagta tacagacgag gatttataga attgtttcat 39661 tcgtgtsaaa cagtcagata cttttatcat acaatagtta gatgatttta tggatcattc 39721 ttatctatag tattcggtag catattagta atgeatacat gatttttcta astccatast 39781 acaegattca tatatttcag ctaccgtcat ttggtgtttt gaegaegtgg tgsasttatt 39841 tatagattta tagacttata tagattgtaa caggcattat atagattttt taggatatat 39901 ctttatatac atattactcg catttacaaa atttatagoa gtatctsata cgsastcaga 39961 ttcatgagat tgtaacacag cagatttaeg aastgeatat ccagateact cacagttatt 40021 gaccgattta aaaagtatag ctgeacgaat castsagttt ccaacttatt tsaegttatt 40081 tacgtttatt aagsacttcc aagsaastsa aaatcacaca tcatttagtc taegattggc 4D141 ttcagatatt agtatataeg cttcttgttc catgtcaaaa taatatagta tatteattgg 40201 tsatattgta tatttattga atgagtgtat tattatastt ataaegtttc ttataeggsa 40261 gsaatatgga ctcgttatga gatactttgg attgtatttt actatsattt ataggattat 40321 catcggttaa aacggagtat ggtagatgac attcatagat gtatcatatg tattccataa 40381 agagactcgg cgatccataa tttatcatat gtattagatt catattttgt ttatacgoac 40441 aaaegtcatt tagtacgatg ttgtcaactt ttagtgaaat cagatatgat acagtatatt 40501 gtgtsacttc tttagsacca catgttataa ccatattsac gggtgtttca ccaaatacat 40561 ttctgacatt tatatcogag cagttgtata atastsattt catsastatt acatattgta 40621 aactggctgc astaaagata ggagtattac ctacatagtc aaegctatag acattagatc 40681 cattattast tsatacaaaa gaggattcat aattaegttc ttttatggat aastgtsacg 40741 atgttatacc acagtgtsat tatttsatgt ttacgtatgc gtttatgttt atsagteaca 40801 tggtgacgta astattatta cgttcgacag ctaegtgaat aggagatttt acatgattta 40861 ttatatttac gtatattcat ttatctaata gaactgacat aacattatgg tatttattgg 40921 aagtagatag aaastgoaac atactatact tgtttactat ggatatatca goattttttt 40981 ctsaaegsaa goataccata tagtsattat tgttacaaat tgtatagtat astgatgtat 41041 atcatttatc gtattttaca tttatgttsa ttcagtgtaa goatagtagt tatatcattt 41101 ttttattttc atgtgttata goactatgta gtsacatata atcattttta tttattatag 41161 atccagoatc tsatsatatc ttagctatgt tgaegtcatc tacttatacg gagtatatta 41221 atsaagtata tcctaeggaa tcagatatat ttatgttaaa atttttatat atsaegatgt 41281 ttactaaatt gtgatagtgg tttsaaacag ccttcattsa catgttsaaa tgtttataeg 41341 tattsatatt ttcttgttga tttaaastca tacgtactac gatatagtat ttteattata 41401 tagactgttc taatagattt atacagatag gttagtgtsa tccaaacatt ttagttttca 41461 tatttgtatg cteastatat ctatatagta aaaatagtcc attsaetttc tattttsatc 41521 aatsatttac ctcgcattag tagattatta gacaaaaagt acatacctac caccagtcta 41581 acaaattsaa tagoacatat agtattactt cacagaagat aagacattga tatgttaata 41641 tcattcatat aatattaegt attcagasta taaccacttc aaaatcattg ttagttatgc 41701 attatatsag gtagtatgta ttacatttta tagctataat agacagoatg tcastgtatg 41761 taastttagt actagtggat gtagatactc ttatagtaag tccactagaa tatatatsag 41821 atccatagat tattatttca tatccagatt ttatatgatg astacastta tttattttat 41881 ttagtctesa cattcatata atgttactag tatatattsa gttteatagt tttatcatta 41941 taasstttat agsatttggg aacatggtat gacaagaaca tsastatttt atattgttta 42001 tatagttsat cacatcatta tcatgttcta attattttat gtttatatcc attgtgatta 42061 tataagattt taaattgtat tttcattast taegtacgag aaateaaaaa tacgateata 42121 ttatacttgc tatatgtagc aatactattt tttatatata tactgttata cggatsagat 42181 acaastctta ccatattatt tggatatsac actatacatt ttccatagtt atgtastast 42241 astccacagt cttccgsatc tatacateat attatsaast ttgeatagtt tcacacttat 42301 aaegtatsat cattaatatc cattacaagc atgacgtgag ctaastattc attattsaga 42361 agatactgag atagaatgtt agttsatgtt tcogatacaa atatattsat aactttagta 42421 ttattgatta atatgteaaa atatgttatc cttgeacatt cagtatatag atatatatca 42481 tcaataaaag atatcatgtg ataattcata ctgtatatat aegtatasta tttattatat 42541 ttcattttca tgacattatt gtgacttttc agacttttta ctcaagatta ttacgttata 42601 gttaagoast aagtgtagag aagsaacgac cataaagggc gatatacaag cacatattac 42661 agagatcata ctattccaag ttagaaagtt atacacggat aacaagacat tsagcgagga 42721 astgatagoa cttgtcatta acatactcat gatgtagast actaaaaacc atgacatatc 42781 cagaastast tgoaegaast aaaaaataat gatatgtaga ctgatatttt cgacagaggt 42841 catcaastac atagoatgac ccatacaagc atsacttata gatgatagoa cacatataaa 42901 gtagtattat tttactaegt ggtatttatt atatcatatg tsattgtsaa aactgtattt 42961 ttatattatc tttacgacta ttsaccatsa cgtsagagat attagagsat aagsatgatc 43021 goatatatat tcgsatagcg tcattttaat catgtagatc caastcatga attgactata 43081 tcagttatat tgatttcatc tsaagtagtt acttatatta tttttgggta tgatattttt 43141 tagastataa tttgagatat cctatcaccc ttacatacat taaattgagt.tgatcagsag 43201 ttsaatasta aaacgcacac gtttcatata tagtctgagt caattacgac agoacatacg 43261 tatataaaat asttataagc aagacaegat ctaggagata ttatacogta gtatccgtta 43321 ggtattttta gaattatatc tgtttttatc agttctttat tcataggctc tattacataa 43381 tcatacgagc tatataagtc ataacaegct gaataactag tatgtttata tggtsacttg 43441 gacatatcag aasttttata tactgttact tcatccattt aegaegatsa cttatacttt 43501 castttagta atsaagtata aaaagttatt acatatsaaa ggsacatatt ttsaaaactg 43561 ctagtgsagc aatgatcaac gaggatgtsa aastacaata tgaagctgta ttgaaastat 43621 acgaatagtt tttatatata cgeattccat tccasteatc ttggtatatg aaccaegatc 43681 tatatttaga tagtatggca tcagttatag cttatgatat tattccatcg tagtactgag 43741 gtgsagtatc ttgtttaact tttttagsat agtatgoaca aaeggoaata atagttatta 43801 ttatacacca attsatttta tattateata cttgagttac tataaegtta aastcastat À À 43861 tcatagatat asttatatca asttcattat asttggtttt tattactgat ttacacgatg . 43921 catttagaac atcataggat atagaatata ttacaaaact ttttattggt ttatttgtgt À. 43981 tatattatat gatatagttc tgtatcatat tcaaagagat atsatsagtt tagtatttca 44041 tattactact agacattatg tatattatga ttgatactat cttgttatag cttcastttt . 44101 ttagsatgsa tatataegta coccaaagta tatacaattt catgtcactc tgoattgtsa À'.. 44161 tatgsaasta astggttttc caactacagt ttagatacat gsagsacagt ttatttttgg 44221 gtattagtta ttagtaaatt caagttatat atatgtattt aaactsatgg attcagoctt 44281 astttccata atagaagatt gtgatattat ttcaacaaat aaagtagttt ctgggastac 44341 atttgsaaac ttastttcca taaggttcag gactsaggat ttsagtsatt ctaegatatc 2 44401 atsagacgat gacatcttta ttttaggast tttaegcatg tgttgagatt ttttcatatt 44461 actattatat atccastata ataagatatc tacgttgata ctattttcca atsasttgsa 44521 tatatattat ttatattcat taggagatat cgtagtsagg atatatatgt tgatagatsa 44581 tgaagttatt acgacgatac atcatatatt gtccaatatt cttaacatat geagacgact 44641 cttagagtag aegagastgg atacastttc cacagagtta tgaegtttcc ttatttgttc 44701 ttcggtagga gaggtsaacg gtatattcca tagagettca aattataaca cgttattgsa 44761 tttsatactg caacattatg tttcatatac ggtacatgtt ttatagcagt tgtagagtat 44821 gttttttgta cgttgattga tacatacatt atttsatcat agtttacaga asteatctat 44881 ataggsacta ttcatattat catttatttt tttcatgtat agatatatgt ttgggoattc 44941 taLgtttast atatcatata ttttatcagc tgttgagtga tcagttagtt tactcaaegc 45001 goatsaagsa gaasttatac tacaaggtgc tattattata ttttcagtac ctgtagattt 45061 tatatasttg tatatcttga tagatacatc tsactgtatt tttatgatat ccatacagat 45121 astastttgt attsatagat attatttcag tttatatatc tatsatatag atgtatatat 45181 aaaatacagt aatttttatg aattttcatc atccaaegag tcatagtatt castatctcc 45241 cattttsaaa agattatata gtataatcaa aggoatsagc gatataasta ttactagtag 45301 tgataatata taasttatca tatgacatat cgtaastgcc caegtatgtt ctttttatat 45361 taaacacact actacacagg tagtatatac cgtatttaca cogtatgtta tatagtagta 45421 tactgasttg ggatatataa cttttttatg tgagttetta gtagattttc tacataccat 45481 aacttttsac gagttatata tatagatatg agtsacatta tggacagagt atttgosatt 45541 atttagataa ggteagtttt ctttatgttt atttatatca catatatagc acttataatt 45601 ataggtgtct aatsatgtsa cagatsegtc ttttcatagc ctgatcactt tccatgattt 45661 attactgggt atcatatatt cagatatttg atatcacaaa gtatactagt ctatgtcagt 45721 tatcatacca aaacgacata caatattogg agsaataggt ttagoataga catggtacaa 45781 tacataaagt atsacattaa taattattat aegoatgatg gtcgagggta attsactacg 45841 tatagtattc tacggtttta tgaaattatt tttatattta ttaattgtgt ataaaaagta 45901 ttattcttca ggaggagata tagsaacagc gtataactgc ttastatcat ttagattatt 45961 agcagtttca tacgttttgt cttatattat cctagsacat ctaggesacc gtatagatat 46021 attagaagac gtatgggtag aagatctggt gsattcagat ccasttattt cccatacagg 46081 tgctsatgsa atatctgaga ttatcaegtc ggggtagtgt attttattsa tagatsacca 46141 atcgggsatt gcatttatat cgaaaggsac tacagsaaga ttatagttsa tttcatgsag 46201 ctatagatca gtatgaccac cagsacactt tgteacagtg caccattttt cagattttgt 46261 atagtagoat cccataegaa aactggatsa astaccagac ttgttaccct ttccgtsata 46321 agoacacaaa actactagat cagctttatc cgccateaca catccatcta agtagtattt 46381 ttttattttc agacatatac gcataccagg ttagtataca ccttttgcat ctttgagtac 46441 aaacacttat atatttttac ttastactat gtgtsataat ttagatsatt cttcatcggt 46501 actastattc tttacttatg aaegtsaast tctattaggt atttccttta tattagcatg 46561 astastattt cgtctttcaa ttagtggttt atatataagt acggtatagt taaaatacag 46621 acagtagaat atgaagatac atacacaagc gttatggtac atactttttt tgttsatacc 46681 tagagtacag aaeggtagag gttgattagt ttatgtatct attagtatea tttcaccatc 46741 tagsatcatg ttattagagg aaggsaaagc tctatagagt aattattcaa agtcagteac 46801 cttatgaggt gtastaggtt tsagacttat actsaastat ttaaaatttt tatcatgttt 46861 atgtatttgt attctttatc catagtactt aaactctaca attataccat tagggoattt 46921 ttttacagat tccgaaaatg tcttacacgc ggatgateac ataggatgta aeggoaccat 46981 tsattatatt agtggtttaa tattatattc caaagatcgt tgtactacct gttataaatt 47041 attacataat ttgastattc catsagagtc tttatggagc catgatsaca catgttttgg 47101 accastgttc attcgtaast catgttttat taatattatg atatgtagsa gatcattagg 47161 tgtacatatg ggtattattt tttttatttc tttgatttga tcattttcte tagttactgt 47221 agatsatatt gttagaaaac aatcaacttc atgteacgtt astgtacttt ctgtggoata 47281 atataccaca gatttactat tttteagaaa tgsacatatc acatsagata catatcatat 47341 attsattaca tatttataca tttcatcagc atcatgacaa astattttac taastsactt 47401 tactsactgt ttatagttta tattataaat tagtttacoc gttcaeggta gteatsactt 47461 tgtastsata tatacatcat tatsatcacg acagagatgt atesattctg atattagttt 47521 tgttttattt acatagattg attatgtgga tatagatgta catagttatc teaattattt 47581 castgttact tccatgtatt tatsatsagc caggtatttt ttacgttttt attcagggtc 47641 ttttattttg cacatgaaaa ccacagaacc tgttttatta tattttatta cgsatatesa 47701 aggtatattt atatggtagt tgttattaga tattttttcc catttatttt ggtcacatag

47761 tacastatta ttatttatsa aatatacttg tgatttsaca aacaaactgg tsatagsaaa 47821 cttgtatgga cteactgatt tcatggsaca attttcatca aaaatatcag ttatacatag 47881 ttatacaaag acagacttga tgttatgttg tgtttgtata gesasttttg ggatactaac 47941 tgatatttat gsatatttca tgttacttac tcctatatta gaegatsata aaattagagg 48001 cgteatatgt ttttccaast atttgsastt cttatacgta tcggagsaga aaagtsacat 48061 actataagtg ttatgoaagt aaggtatgtt astgatattg gatttsattt catgacaata 48121 catatgtcca aacattccac tcgteattat gtacggeaeg actttagtta astacttagt 48181 cacaaaaaac ttatgactgt cattatatga aaaeggtgat tcocatsast cagsatactt 48241 aatattaast agsatgatag cttatggagg tttcaggata ctagateaca tatattatgt 48301 attatagttt asttcactca ttttattaca tsatacagta acatatcacg aaaccastga 48361 tgttatatta gatttactta catacttatt gtaactatca tgastacgtt tgttatgatc 48421 tatsaagsag atggatgtat attatgttat agatagcagt tatttaagta tcttgtctgt 48481 attactatca tagtattcat catagtatsa aggtagoata tatastsaat ctastagttg 48541 atttatagat ctatcagtac tagctttcaa tsacattttt actatsagoa tsatageagg 48601 cggtgatatc actatatttt tatagggtat tattttagta attagttagt ageatttagt 48661 agagatsaaa gacaatttgt tgttgatact gattacgtta ctcatgtttc ttgtttatgt 48721 tsattaacag gtatacactt acastsagtt tsatteactt ttaggttttt gtgsagsact 48781 tttagattat agttcactta tccatsattg ggtattagat ctagattatt cccatgtata 48841 aagggggaca tacacaaast ctttaaatgc tttgtccgtt tatatagtea atgtagtaca 48901 ttcattastc aaagtatsag gatttagtsa aggagtgtaa gsacaastag gtgatagtsa 48961 tactattaaa catttattaa tattagagat aaacattaaa caccataaag gsagacatgt 49021 attcagtaga tccatcacta attgattsaa gaastgoatg ttsaastcat gatastgttc 49081 agtaggagag gtatcgtaac agtastacac gttattgeag agaggactat gttgaccatt 49141 ttatatcata tttattgctg ctsaaatatg catccaegat acgtttcatg catagactat 49201 gctatgsast actttatcat ccgcatattt atsaattttc ctgcttttat aegatattat 49261 gtatsaagtt tatagtactg gacagtattc tcagaaaaca catastgggc gtagagoaca 49321 agtgoatast ctaagtccta tattagacat agtacagtta gattatagta tatatttatc 49381 agatsactgt ttactaagag gatsagactc tttatggtta gattgatast aegtattatc 49441 gtttcatatt atcatagoat ctcogagaaa gttaggacat acagoagsat aactactagt 49501 atatactaag actattacgc cgttatacag acaagsatct actaegttct tagttcagtt 49561 gatattsacg tccattatag agtagttagt aaacttacac gatacatcat ttatagsagc 49621 astatgsatg accacatatg ctgatatsag cgattagtcc aaagtacttt tatttctaac 49681 atatccastc aegggaacta tatttattat attacatttt tatacaegat ctagtsacca 49741 ttggtagatt ctastatagt aaacacgsac ttcttttaaa gaggattaga acaagatsag 49801 attatttata atgtgtatac ctesaaatcc acacactcag gttaccacgt atactagtgt 49861 acgoattttg agtatteact atatsagacc aaaattatat tttcattttc tgttatatta 49921 tactatsata aaaacaaata astatacgaa tattataega aatttagsac acgttattsa 49981 agtattgact tttttattaa cggagtgttc ttgtasttgc cgtttageat agtctttatt 50041 tactttagat aactattata tcatsacagt ctcattattc caacattatt cagaagtaca 50101 tgtgtactta cagaagttat catcatagag attatatatg aegsastagc acatatcatt 50161 attatcaggt ccacaataga cgatagtttt gttatgttta tttacacaga cgteattggc 50221 ttgatgagat tatatgggac aacttsaaac atgataggat gatgsactta aatacacatt 50281 tctactaaaa ggttctctat ttattsaact acaggsacat atatttttag gaacatcgta 50341 tatatatttt tgtaggagtt tattttatcc acogtsaacg cagtcastat ttgtccatcc 50401 gcastgaggg tatatactca ggagacaact atagoaegta cagacgtata astggosaaa 50461 tgataaeggt agttagatag tactatagtt gtaagataca astsattttt ccgsacgttc 50521 gtcogacact agagagagoa caggagatgg atattgtttt agagttsatt ctatgacatt 50581 tataactcca tattagtaaa ctactacttt gtgtatttta ccataggaeg tagesagata 50641 gaacgtggta acactgtagt ctttatgttg gtagtttata acagctgtat teattactat 50701 atgtgtatac gtatattttg ttttsastat aaaatatcat tttacaccat atsatgtttc 50761 aggatataaa tagattactt caaaagtatc tatgggagtt gatgtgttta aacaegtacc 50821 tggcatsacc gacagsactt taccacogat atacactttc agtggagsag tattsaagtt 50881 attatgtatt ttatagaact taaacataca taeggoagaa tagttccatt cattaaagea 50941 tagtccatat atastagttt catttggact tttacatttg attaegacaa catattttag 51001 atsattsast cgtacattca gatattagoa gatcattatc gatttcagga aggtagacca 51061 ttttgeacac gatsatgacc cagatcatcc ctgatagtgt ttacatactc tagatacttt 51121 tgacattcat tattcatgga agastatata tattgtatca tttatactgt ttgtttattg 51181 tagagatact aaatgtacaa atttaggatt tttcattgta gsactagatg tatatsatac

51241 aggattacat aegattctac taaatcatgt acttagatga ctatattttt ttatagttga 51301 gtatatttat ttaccatata ttaataccag tcatgtcata tcatsactat caggagagag À . 51361 tcatatacag taaggagtgg gttattttat gOtacagttg atataccagc atgtgggtga 51421 actagsattc gttccacaca ctagsatttt gtcatcatat ccacatatsa atgtsatata 51481 attagagact gattgtgtag atacattatc gggtgsaaag tccacogtsa tattgatttt À. .. 51541 ataggttgta tttaccacgt atacagtatt tgttactcat ateattagtc gggtattaca 51601 atcagtgaga tatatsacca catcttccat ateagtttta tacatsaact cgatattatt À 51661 ttcagtcaac ttgatattea cacggggaga tattatttta gagatattac acggtattac 51721 caaaegtata aegatgatga tacttatata aaacattatg gttggtatac tgttatattt . . 51781 tatsatacta ttgatatttt gtgtatagta tagattatat attcatatat tacgtcatat À. À 51841 tsatacatat ctatttttta tgttttacga tatagatsaa astgsatata ateattteat . 51901 tacttattag tatattgggt tttgtaegga cattatggat cacaacaacc cacatcagsa À. 51961 ggtttaggtc cggtatttac gactttatca taggtagatg gaggttgtac attcacttat 52021 gggggagast cgattgttgg tttttcagat ggagattcca tggatttagg gttcasteat 52081 attastgttt ctttttcatt tttsatgtac gttattttgt astsatgttt atatsastta 52141 ccatacttta gatattatsa atattgsagt aaaagsatag tatsasttac ctsacataga 52201 acatcatgtc cacgagttta atagaattat atsattggtc tattaccata cgtgatsagc 52261 gtgtagacaa ttggatgtta atgsattatc ctattcacac astatgtata agtactttat 52321 atataattat agtatggtta ggacataast ggatsaaaac tagaaacgag tttaacatta 52381 gatggttact agttttgtat aatttttata tggtatttat tsatttctat attctgsaag 52441 asttatttgt atagtaggoa goaaaeggtt atagttatgt ttgacagact atagattatt 52501 cagataaegt tcaegaggtt aggatagaca gagcattatg gttgtactat atatccaaag 52561 ggatagsata cttggatacg gtatttttca tacttaggsa aaasttteat caggttagtt 52621 ttatacacgt atatcatcat tttactatgt ttactatagg atggataggt attsastggt 52681 ttgatggagg tcaggoattt tttggagatc agatsaattc ttttatccat gttattatgt 52741 acacttatta tggtatggac gattgtggtc ctatgttcag aaagtatata tggtggesac 52801 gttatcttac tataatgoag ttggtacagt tccatatagc tataggacat actgetatgt 52861 ccatttacat agattgacog tttccaaast ggatacagtg gtcagttatt atatattata 52921 ttagtttcat attactgttt ggtsacttat attttagaac atacaagsat tctagtsaga 52981 aggttsaata agcatatatc taaaatgaca taeggttatc acaastagea atttatataa 53041 atagosastt ggtsatataa atsatsatgt ataaaaaagt caacatttat ggtatagtta 53101 tatcagsacc aaaataggta aaaaasttta agacaaaaga ttotatagtt astgtattgc 53161 cagastacta ccatactatt gatgacaaaa gactagaaat aegtaaagat aaagatsatt 53221 gctggttatg tsaacaagat atgaatacat ateatcacta ttttatagag actatatacg 53281 gtgatcatat aggggtattt tgttccaaaa tttgtaggga ttatttagat aacatgatea 53341 aaagtgtsat agctttacga gsagaacata aaatatatat tatgaegttg gaactatatg 53401 aaaagccgga agaagtatta gsagtsatca acgatataag acacaaagaa ggsatatatg 53461 gsagctgtat acttgaatcc gacaaaaata tcattaaatt aacactaaga tgccattgta 53521 atactsatta aatsattttc acttactata aRtoaataPt rtataabaa "t Àa 56881 atgttcatat atcgttsaca atgaagcatc tatattcgag gacgtagaaa atactactat 56941 ttttgctaaa aaaactgtac atattaagca cgtgtttatg tataaaaaac aagaagaact 57001 atatatsaaa gccagatatt tagaacgtea actcggoata taggtattca aaatatatca 57061 acgtatggcg tctacttttg tatttgatga tattccagat aagsaaaagt taacageaga 57121 agaatatgaa aastttgtag attagttatc tatagatttt aaaastacat tatacggtsa 57181 aaaaatatat aaacagtagt tagatatatt atcagctgga ggtacastta atgatatcaa 57241 agacgttsaa gatatagsat tatatsacta tttgtacgag catagttgta asttcacatt 57301 cgtatgtgtt tcaatsatac astctsaagg aaastgtatc gtatttgsac cttttatsag 57361 atagtcagga atagsaatat tgctacasta ctttaacgta tttggtatsa catatataga 57421 gttatattat aggaegaagg atattagatc tsaaegagta tcagatttca atsaegtaga 57481 tsatacagat ggtgaaatsa cgsaegtatg cgtattttcc caaagtggsa acgaeggtat 57541 aegttttatt tctatsaacg atatttttat actggatatg aegtggaacg aagoatctht 57601 aaaacaastt ataggaegtg ctataegcat tsacagtcac gttaatsacc cgacageacg 57661 tagatacgta aacgtgtatt tagtggtagc taaactatag tatggtagat ctagagtgga 57721 cgatattttg ttagatatta ttcastctaa gtctsaagsa ttttcacagc tatateaggt 57781 atttaaacat tcgtatatag astggatcta ttctsactat acagattttc agacagtgga 57841 cgatgsaaag gggtttsaaa astteatttc taggastatc atactagatg aaastacast 57901 aacaaataaa aaaaagttaa ctatgggtga aastatatgg tattcatttt cttcttattt 57961 agtatccatt cacagaggtt tcaastccat ggatastsaa atttaegact ctgeaggatt 58021 tttcatcaca gtattaccag ataagactac tatsaaaata tatgsaggaa aattasttta 58081 tatattaaca gttagataga tgttaactat tgatagagga tgttcttaca gagtttatta 58141 tatatttast tacattagta tacaastast ctttgttsat atatcttgcg tatatsaatg 58201 atattcattt astttatata ttagggatga atctattcaa tatttgtata ctagtaegat 58261 ctgtttatac gtaaagggat atsacttcaa aatatttatc tatcastotg tagtatatag 58321 aaccgtatac aaaacagttc ttacagatag cgagataaga ggsatagata ttteattatt 58381 cttttatttc tattactaga caattagtta tactttccaa gtattttatt ttaccacatg 58441 ggsagattat atctatatgg tttgtattat agttattagg aagcgatagc ttatsactta 58501 atatatcacg ttcgatgtta ctcatatact ttgsatattt cttsaagagt cttattttcc 58561 gtcgtttatc ttttgtsast gatatttatg aaaacaagaa actattgtat ctatggoata À 58621 aaacaaactt gtcatatatt gttttcatta tacatattac ggatagtgga tatttagoat À . 58681 gtagtttgac atattcatat gataccagtt tgattttttg tatattatca gsatatacag 58741 acggactsag gagosattta tttttatsat actcacacat atttatatgt tastsaggta 58801 ttatsaataa aatgosagta ttagtatttt tcattacttg atagatcaaa tsatgatcct À. 58861 asttatttga tttatatgtt atatsaaggt ttastgattt ctgsatagag ttggtatata 58921 aaacacacta tacastacac ataaastgtt ctaegsagta tattatattc tatggteagt À 58981 tttaatattt tattaccaaa tgtttttata gtaagtattc catagatttc ttcagatagt 59041 tctctactca ggoattgata tattgattat ttatttttaa ctattcatcc tsatsatact 59101 aactattcaa agttgttgsa tccgatatat gtgsatggta ctattgatat astgatattt À 59161 ctttastttc gttattatac atatacttta gatggtttat atagaeggct astatttctg .'. 59221 aaaegattat tatttttgat ataacagatt gatacatsaa agacgttatt cttatacaga À. 59281 ttataggtat attatatgat gtastacata acgagaatat gtgsattagt ctatagatsa 59341 gtatatattt tatgttagtg ttttctatag ttattattta tttgtttaga aagteateac 59401 acastattta tttttttata atatattttg ttgttatatg gatatataga acatgatatt 59461 agtttttata gttgtttatt tttcacttat gtttgatsaa ctatatatag tgesatagoa 59521 tatcgtaaac tatataaaaa astactagtg tatcacattt atgsatatat ttttttsatt 59581 aagatatsaa ggsatatatg atataattea acteataagt taaegattat atagttaaag 59641 tagsaaastg tattgagsaa ttattttact ttatagosat atatacagag tcactgagat 59701 gatatattat actatccatc caccgtaegg actttttttg actttgoatc tttccatsaa 59761 atgtgatcat tcatatgsag tataactatg atcagattat gtatatgata aeggagatsa 59821 tgattttacc agtataastc caacatttcc aatatatcca caggtaacta cgoacatata 59881 cttacatgtt gattctcatg ttgtaggatt tgggatactt aDcOatcata tcactccata 59941 agtatgteac agtsagttsa ctcacgaagt ctgttgttcc cattttagtg tastaccgtc 60001 astcttccac cattttatgt tgacttggot tataccatat attcgtaggg tactsaaagc 60061 acattcastt tttagaggac gaccatcaga catatatact ctagatettc gaggggttat 60121 acttacttcg ttatgoatgt aggttttttt tgaaacagta aacactcata gattcatttt 60181 tttataatca gagtagacgt ttatccatac aacacacata tatgsacatt ctgattattt 60241 agatacattg gatatatgta goatggtttg gaccacttgt cgtgtagtat cacaegttgt 60301 ttttattcct tgagtsactt ctcagtcacc ctgttgacac gatacastta ctttatcttc 60361 tccagcacac tgatcatatt tsataaaaca agtsagattt atatcactac cttcaggtac 60421 gagtacatag ggaggtgatt ttacttatac aaaagttttt gatagatata tsaagcagag 60481 aastattatc aacgtcaatt ctttatgtcg aatactattt ttacatatca ttgtgtgtat 60541 aactaatatc tttctacatg ataaagastt caatatacta ttsaaatatt tatagttatt 60601 tttgatttta caastattac teastgctat ccatgtttaa taagatatac gttacatgat 60661 gtaggtatta tgtsasttsa tatttattaa agtattattt ttcasttatg ttacataaga 60721 aaacaaaaga tgattccatt ccagattggg cttattttsa cataacagta actgtacttt 60781 cattagagta gactttaccg ttatttatga aacagtattt tgasttatca tatgaaacag 60841 taccggagtc gattatgatt ttacaaatta gatcactaca aactacagsa atatcagatt 60901 cgtctgtsat agttagtata ccagsaacta tatcacatac cttatagtat ttatsatata 60961 tgttacatgt cacatgaaca actatttcat tattaactsa ctcogctsat ggoatggggg 61021 tatcttatac tatctgtatc tttttggcca taaacacaga tgtttcattg tgtsastact 61081 tatttateac tgcctttttt atattatcca ttagatataa atttaettca tggggttgta 61141 tsactacggg tsaatacgag tttgtattsa acaacgacat ttagttcatt tatsaastta 61201 atcatccaag astattctgt aaacastaga ttgeaeggta ctactatsat atcattttta 61261 tgtttatata acaatgattt ttcaastact ttattagtaa cgsagaastg gtagtctgtt 61321 atattctata tatatttttg tgttttttat ttggatttaa aastactatt taccatttta 61381 aaaagtttag catcgtttat acttactata gaattgtggt aaaaaaattg tataaccagc 61441 tcgactasta caacatcagt tatataagga tggggtgatg atctatagtt tatagatata 61501 tattttagta tggsatesat tagttttgtt tctttagttt taaactttag ataaagtagt 61561 tttttgatat cgsatggtaa agtatttata tcatatatac tatsatcatc tagagaagtt 61621 attgtatagt taaaatatga ataaacagta gatsataggt atacgtteac aggtttagsa 61681 acatatttat acgagaactt tateatagat ctacacaaaa tatgattgta ttgtgaaaaa 61741 gtatcaggta tagtcatsaa ccagatgttt cttacttcat tcaaagtata tgattatgac 61801 atsatattgg aggaaastsa aaacatsatc ttttatcagt tatcattcac tggggsatta 61861 tacacttcca atsastattc tsaggatgac ttcattttac tagtgactat agosastgtt 61921 tteagatgtc cgtttatcat ttttggattg gtacattgag aacaggagta ttcagsatat 61981 ccgttgttsa goatgatata cttgatgact astccacagt atgtagsatt agsaaastag 62041 atsaastttt tacccgtaag attcaegata gtatatatea astatttsaa ttttgagatt 62101 atattaagtt tagttsattc gtatcogtat aegacacagt cgtttatttt caasttagga 62161 taaagttctt tatcatgttc taegastsac agttatsaac tattagacaa attcaaaggt 62221 ccteatacag ctsaagaaac atttgtcatg tttttttcaa acatttcatt attgoacast À 62281 ttcogtacgt ttatgtagtc agtttcatgt agtttagaca ttttacasta aactactttc À . 62341 gtatatsaaa actatttacc gtgsaagatg atactaggta gttcagtatc acataattca 62401 tagtaggata tattattatt cagsatattt tttsataegc ttacacattt ttagtttsat À. 62461 attatatgaa atactttatt tcactggatt atastatagt tsaagtttat acattcatcc À. 62521 gacataatac tsatastatt agatagtgta ataggtgtat tagtgatagg agacoctgat 62581 agtsaaagsa aaggtacatt attattattt ttsatsatag tcattsattc acatgtattg À 62641 tttcagsata tgttatgagc ctagtatatg atgsaaatag agtagttgta cttagatsaa 62701 goattgtagt tcactacatt atagttgtag ttsagactat agsaattsat cgtagsatsa . . 62761 atatgsatat tttcasteac atattatgta ttgatgagat tagttgacaa atatsastta À. À 62821 tacgtaaata tattsagtat attsatatta ggtaccasta tgtsaacatt tttesacttt .'* 62881 gacacgatea gtgoaaatag cagtgatata atagttttcc ctgacaccat aatatgaaac À. 62941 aacaaaacac tttcattatg atatagtata gtcattaaaa gatastccaa ggtagatsat 63001 tgatgaggta agatattagg aatgttatat atgtgaccat taaagagttc aagtatttat 63061 aggttcattt atagtattca aatattatat gastatsaaa gacatgtatt cataggccaa 63121 gttcatatat tttttattat tcatgatsaa actgtcastg tattgaccgt atagttttac 63181 attsaaatgg agacttsatt tatgttgsaa tatOtttast tgtagtacag gtattccatc 63241 atagtatgtt atatatcata atttcattsa tttatataca tatttcacat gagtageatt 63301 actaggsata atgagagatt ctacttttaa tatgaactta aagtatggta ttttatatgg 63361 tgttggtsat attcttsagt taggaacatg atatttacta aaccatcata aaagtatttt 63421 cagsaaegag tatatsaaat asttagattgastttttgaa tcaagacttt cgtttsacgg 63481 tttsataaaa tcatactttg agttatgcac cttatttttt gtattagtaa agtgagtttt 63541 aaasttaact agagatatcc ttatcattat agagttatat actttataga atacgggttt 63601 atagttggta tatattatga tagtagoatg attcatgtta ttgattttat tagastsaca 63661 agatattcat actacacagg gttatgttaa cttattgata ttgteggatc ttattttttt 63721 ggacgtatta caactsaast caggaagttc gatacaaast actactatat tcaagtgoat 63781 gttagagata aagggattag gacatttatc catttgttat gttagsatsa catgaccggt 63841 ttatagaaac atattatgoa tgacagattt tagtsatttt ttagtcgtag attttccagt 63901 agatgtttat ccatsaaega agsatatgoa ttgttttgta gtacacatga gacaactcga 63961 aegtatatgt tagtagagtt ctatattttc aaaattttcc tttgtatttg gttggatatc 64021 gtatagtata gacattagtt ctgtagttat atcatcaaca tttatacatt cttagtattt 64081 atacccagtt gatacagtac aaacaaattt ctetgagtca ttacattgat agsatataga 64141 atattttata tcatacacac cgttaagaaa ttgtaatttt tatggatsag tgtcggtttc 64201 tatagtatat atcaacatat ctttsaggtt atgttatatg actttccgat ttataggaca 64261 tagtsacaaa tcggtacagt cggatgatsa gtgatatatc atatatagta ttsatttggt 64321 tatattatta tcatattcac acattctcca cacgtttttc aaccaaacta gatattctcc 64381 tatatatgaa acattastta cattsagatc tattatttgc tgtgaastac tgsatsattt 64441 attacattat aaggaaatag ttttsatatt acagatattg ggatttcogg atttatatat 64501 tcttatacaa tagttactaa tcagtsaqtq atqaqqatqt ttatqaasta chttthtaca gLj 67861 catctatagt attattaaat tattagtact acogacgtac aagtattatc cattttacat 67921 atttttaaat gtatcgtacg tagtatacga tactcgtata goaaaactta ccatactata 67981 gcatataatg tagttattat atgttatttt agoaacttat ttttatgtta ttsatactgt 68041 tattactagg tgatttacca cgaggatatt cttccaacat catagttata agtctgaegg 68101 caccaacgtt cataccgcta caatttggaa atatggcacc aattgtttgt ggateattac 68161 ctttatcagt ctcattcact gttatgcaat aagttttatt ttcactagtt gttastaggt 68221 agacactgtc cgggcatcag ggaccagttt tggtacastt tsaaactttc caaggagagg 68281 gaactggtcc gtatatgaca ttacagcaat catctctaca ctcgtaegtt agtataaaag 68341 gattgtaaaa acaggatcct attacagtta acaegtatat agsastatta ctctgoatat 68401 ctgcgttsat tsagatactt gtaaacactt aatagteatt catatgttaa tggatatatt 68461 atttttsast ttttttaacc ttttataaaa acattatatt tcaastcatt gtacacastt 68521 tattctgggt tcgttcttga gttatsatsa cgtgttsaca atttcgsaag tttagtatgt 68581 atagasttga cgattcctag cagctggatg atagactact actacagtag ttggagagtt 68641 tsatatagat ctsaasttcg agaaatcgat tttacataaa aegtaaaaca cggatacgta 68701 ggaegatata tggttgatga aaacatccgc taacctttcc cagsaastct tgtgactttt 68761 tgtttagcat tatatgoaac ttaegtsata gttccacgct astacacatt ctacaaacaa 68821 aaaattgtag ttcttgsaga gtatgacgtt atatcttcta gaastatttt ctgatatagc 68881 ctteatagtt ttttttgaaa aatcaggaga ttagsaaggc acgcaggtag catcagtggg 68941 gtsaggatat atacagacta tacatactat tttatatttt agtgattgtt tsagttgttt 69001 aaaastattt tcatgagaeg gtgatgtatt ttcttatagc agacaeggtc ctgtctattc 69061 tataacatca gatatatggt tastastatt ttcacaatcc tagtggtatt ctataggata 69121 cggacastta tttsacttta aegtattcat tatagattac aattattcat atttattttg 69181 ttttcaettt cgctgtatca tgoacgtgat agaacaggcc agtcattata ccacttattt 69241 ttatatagta asttcasttt taaatcatcc cacagttaga cttatttact gatatatsac 69301 atccaeggat tsaatggaag atatttatat tgattattat caggtgatat tactttatta 69361 ttttgtttat ttttattatc catagsagat ttatacttat tatacatast aagttgtatc 69421 gatgctactt ctttccaaaa atttateast gtastacgtt tacastatsa tcatagttta 69481 ttagattgtt ttattactat accaaaagag tatattagta tatatcatsa acogoaatta 69541 ttagttattt ttatacaegt cattagtttt agsatacgta cgatggtgtc caaattsatg À 69601 ttatgtgtac cgtattctcc tatsatccat agtctaaaaa aegttatact gggatttcag À . 69661 aggggccatc ttaaagattg tattaaactt ttatttttac tttttagsat atatgsastc 69721 ttgtatttat aetgatatat aggattacaa atccagtaag cgtttataga actastatca À. 69781 gtaactttta tattagttat atccaggtsa tattcactcg tsatacattt cttagttatt À. 69841 ctagatatac tgtgttttac aacaegtgtt ttattttttt ctatatacca tttacagatg 69901 ataastccac aaccaactag tastgatttt ttattattat gttatataga tttatatatt 69961 aacatgttag agtcgtagta acatattsat atattatatt ttttaccaag agttsattta 70021 tattgttatt cttcgttgtt atttatttta acagttgtaa teactatatg gttagtatgt 70081 tatgsagsat ttatcaccat atggtatata gaggacagtc ttttcaagsa cagatttaac À 70141 ctatatattc ctacattcag tttsatatta tagggtaast ccaaaaccag tatteatsaa ., 70201 tgggeattat gtsattttaa tgatattgtt gtgtatttgt tsactattat tcagttaagc À. 70261 attctsatat taatsatatt accaastttt gatagaaacc tatagastat aastatattt 70321 acgattatat tcttttcatc tatcataast ctatccaatg astsattatt gattsatata 70381 ttagtgtatg tagagatcat gattgtatat attatagaca agtsastttt tatttttttt 70441 tcaatatttg atgagataac atattttata ggagattaaa taaagtacaa ttattgacta 70501 tagttgataa caattsatat attattacgt gattttsaca gttaastsac ataegtttta 70561 tsatsastta astgsatgat gattggatat tgoatcatac catttatast tttaacatca 70621 atctattsaa tggggagagt tttgacttta aaacatatsa agatsagata tgtatatttg 70681 teaaegtagc ataggsatga cgactagatg acaggsatta taeggaactt acaaasttat 70741 acgacaggta tttttgtgat ggattacgta tsatgOcatt tccttgtaac cagtttggtg 70801 gacaagsacc aggtggtgtc aaagsastsa tggsaaccat aaagsastattaggtattat 70861 ttgatgtgtc cgaaaaggta atagtaaata ccatatacgc goatccttta tggsagtggt 70921 tacaaacaeg gactatactg ggagatgtgc coggtcatat aaastggeat ttttgtsagt 70981 ttctsataag tccttttggt tacgttatta agagattaga tcatgsagtc aacactatgt 71041 cgatacaaaa agatatagaa catgttatag aacaacgtgc tsatgaagsa atgactatsa 71101 atagatgggt catgcatgac aegoattgtt ctgaggaega atatatttat aaagatgtgt 71161 tsastgacgt atastaaatg gtatatsact actgtgttgt attcatgtta aateattatt 71221 catcggatga ttataaaaaa atsaastatc tagattatca ctatatsata cttgataaac 71281 attcagatag ttatcataaa acaatatctg gatacgtaga gttesaagat ggtatatctt 71341 gctcgataat agsaaacata asttatagaa tattatatsa aaaactacaa ggeaacaegg 71401 attttttaeg aattsataaa aagastatag tagacagttt taastatesa ggttgttaeg 71461 aegsatacag atagageaga ttagatatta gtatttttga ttactataag tesattcatt 71521 tatsagttta cggattttag tttttttata catgtatttg tttaatattc ttttacatat 71581 tgtatttcta cttsataccg tattttttag catagatagg tattcagtaa agtgatacat 71641 tatatggtat astgsattat cgtatagttt aaaagtatct atggaatcga gatsattatc 71701 ctttaaaaac cgagtatata attattttat ttcgtatatg ttgtaaaggt tatattcaga 71761 aacatctagg tttsatatat cttatatgoa ttatccgaag taacacggac ttataccatc 71821 gtgtttsaga atatcattta cttcatctat actcatttat tgatattatt gcacgatatc 71881 acatatgcag gcattgattt tsatgtataa ttatatttat gttttttgtt ttttttcatt 71941 attatattaa atctsaaaag caastaagtt gttatgtttc ttcaggatga atagttatat 72001 tgtaaacagt aastcatctt atccttttta tcasttcctt gattttaggt tctatagtgt 72061 ttataaatgt aacggttttg tgatatttac ccattatgct acattgtagt ctataacaga 72121 aacgttgata aacagattta aatgoatsat tagtcatttc atgsastcga catsatatta 72181 catctatgtc ctttcttgsa ttcatcacaa acactatttt taccatgatt ggtgatataa 72241 acatatagta tggtatttat ttttatatat tacagatcac gatattattt ttgggtgagg 72301 gtsatcatta atacatgtat tgtatatcac agsagtastt aaatcatgct gtgatactat 72361 ttactatcat tacaaaaagt aetgatsaaa acatccataa ctacatacca cgtaegataa 72421 cgtgataaag aacggatgtg acaatsasta ttttataaat tsattattsa gttsaaacat 72481 tsatatataa tsatcattat tttttgctaa tttcatattt cggactagag caaaatatat 72541 gtaaaaegtt attacattaa ctcaattgat ttsastteaa tsatastatt ggatsastgc 72601 tccaacagtt ctttcaaaaa ttaatttctt tattacgtaa accactsaag atatatgtac 72661 ggggtttgat agaagagact ttttagggtt cgggagtagg ttgatatgat ggtttactag 72721 aegagtattt ttcgggttag ggagagggtt gatagggtgg tttactttag ctaggttggg 72781 gatgtggatc ageaccagca tcattagaag gaggoatagt atcaatatcc gacttctagg 72841 tgggtgattt gctactacct ccagacastg ttctsaatac gtcactsatt aacttagtca 72901 tgttgtccat tatgacacgc atatattagt ggoagataag tagctgactg gtaaagacat 72961 ctttggactc ttggcatttg agtttttcat actattgeat cagtttattt tccatgattt 73021 ataggatata aaaastagta ttttatactc attattttac tgttacttsa actsaastac 73081 aggattattt atattatttt ttatatcatt tcataaaegg ttttgatagt ttagttttat 73141 tatttacast tacttagttg tcagctatac caagctataa caaatgoatg aaacttatat 73201 ctatagtsat cgsattttac tastttttat atatcactac tatagsatsa ttcatcagaa 73261 atsattactt tccaaatgtc agtatagatt astgatacta tatgtttatt tsatatacag À. 73321 tsaaggttag atgattcctg ttttattatc aagosattta tatattttct castaaaatg 73381 tttttatesa acaaatctga tttatccata tttatttgtt ttatsagatt gggagatgta . 73441 tsaaaaastg aactgtcgtt gacttgatsa ccatatatea ctatatattt ttagggtttt À. 73501 astsattgat gacatttgat catagttata gttttgatat ctcagttaca tatgtaacat 73561 astacataaa catggagttt atcaggttga gsatacatat ttatatttcc ctagttgttg À 73621 attacacatg aacatattac ttttttatat tatttatata acattsaatt gattatttgt 73681 ttgataggac agacaacgtt ggatgtasta aaagsatggt ataactcatc ttcatagtta 73741 acacttattt cataaacata ataaagttat atgttgttca tcastastat tattatttta À 73801 tttataaatt catcagtatc tcatagtsaa atgtatacat tattactact attacataaa À . 73861 tagtatactg atgtateact atttaacata tgtatttcca tataaatatg atatttsatt 73921 tatatatsaa atatagatsa astatcacat atsaaegagg ttttttatsa tattatsata 73981 gtagtatata attttttata ttatatatga ttcaaatatt tatatsatgt gtatattgtt 74041 tttattattc gatccccata atatatatgg gagatttsaa tatatsatag cgtctsatag 74101 agatgsastt tattctcgtg aagosatacc tgatsasttt tggsattata acggatatga 74161 tgtactcagc ggtatagacg tsaastccgg ggtacatggt taggoatesa tactgacggc 74221 aegttttcag tagtcactsa ttacttacaa cattaegsag atcatsattt tataegtagg 74281 ggsaatttag tatctgatta tttsacatat aatatatatt ctagtgsata tatatgatat 74341 ttatcaaaga gagggoattt atacaaegga tttsatatta ttaeggagtc tttttctaaa 74401 gsatcagatg atttatatta ctactatsat agatcaggta ctgoaccaga aaggatagga 74461 acagggatat acggattatc tsattatttg ttagatatat catggactsa agtttgtgtc 74521 ggteagaaag tattcacaga tatsattcat gaccatsaga atgatttsaa ccaagsatca 74581 ttastcacgg aattactaga astgttsaac gataccagtc cgatacagat agatcataga 74641 atacaggsac agggacaaga tttcataega cagatgatsa aagasttttc atctatatgc 74701 gttagagacg atggttacgg tacaagaaca aatacgatag tsactataga tagtcattat 74761 agtgttastt ttattgaaaa aaccatsacg gatatggaca caaaagagtt tsaastatag 74821 agatatacat ttagtttatt atattagsaa aagtaagtgt atcaaagttc tttatttata 74881 tsataacata ctgtaacttt atttastata tgtataatct tataggttaa astsacacta 74941 actatcagat ttatcattsa tattattatt actattatac ttsacatatc catctacatc 75001 ctcctttcaa gagsatsacc asttacgtag tggattattt ctgtattata atcagataga 75061 gttatataca gtcattgtta gtagggaggt attcatttat tattttgggt ctttaatttt 75121 aaattttcaa cagtattact aggttcagat aastaaatga ttatatttac aaatatatgc & 75181 attactgtat ttttatacta aacgagtatt atatacgaga astasttata tttttatatt 75241 ctagatattt attaactact tttatatata tgttcatcat goatttcatt tatagattta 75301 attatattat cttctattac tattccttct ttgctatatt tatagatsag tactatattt 75361 gatteagast gattagtast tagtaatacg ttagttattc tggtatatag agsattagct 75421 attacaacat ggtgattata tttatatagc gattgactag ctttagttac teacatgttt 75481 ttataggtat ctsatttgaa tgacactaca aaagoatttg gacaccattc gtatactsaa 75541 tgsastsaca tattagggac ggtttttaac tctaaagtsa tatctgtaga cgastatatt 75601 ttatgttcat acatttagtc ttatggaata tagsastcag aaaeggacgc tgosagatat 75661 acaaeggcat gactacagag tatagataaa gatttagaaa tcatttatsa gaastttaga 75721 tactgatgta tacaagtata actsatagcg agtsatttat tttgttatat agcttcatta 75781 tattttttta aagoagatac aagttgtgta tttagagagt cgttaaagta aacagtattt 75841 ccttatacat tteatgaact castaacata tttcaegaeg gtsatsatct tgaccaaggg 75901 aaaatagatt attcacggta taagaaacat acagsataac cattttatat tsacttttca 75961 acageaatag ctcctatcat acccgtacta aaattatata aaastatgac tggttttttt 76021 tctsaagata ctatagtcac tccagatgtg actaaagata cacgcatgtt tttatatttt 76081 tgtastttta cacasttatt astgttagta gtcgtgtcca tttttttsat ateagsattt 76141 atattaggtt astttateag aaaccastac tttsastatc teattagttg ttatsaacaa 76201 cagttatggt ttcttaastt gttgattcat gatastatta tagtsataat tatattattg 76261 aaatatatag tatagttttt gagatsasta ttacgsataa agcatattca tatcaaegea 76321 acattagatt tacatttaag ttgtactacg catacgoacg aegtacatat tattatatat 76381 tcacaggaeg goattccatt tttaatsact atagagttaa caaaegsatg agaegtagsa 76441 caataagagg accaaaatag tgtatatatt catsaacagc cacteatagc cggatattcc 76501 ttacacttgg tttagsatag gtactgatag taaacttgtt tattatgtac tatttgatcc 76561 astagttata gtttattacc tatgtgatca aagactgtag ttttgttagc gacocatgta 76621 gsactacttt cacaagataa gtatattcat tcactggtat tacatacaga castsattca 76681 tctatgattc gtttaccaeg atgttatata ttcggagtac gagtactaaa aacaacttta 76741 gatgtatata atttatagtt tatsagataa ggattagtaa attggagtsa cgatcacttg --e 76801 catactatac ctsatacaca tatsaagatt agcattctaa asttacaggg gtgagtatgg À 76861 tatgacattc ttatttatat atgsacttac tasttaagta atagsatatg tatcagtsat . 76921 asttgacggt acactgtagt atttgattcc actagtaaac acatsasttc cttaccatta À.'. 76981 tgtttattat ccactsatag ttatataata aaaaatgtag agttttgtsa cggeattgtt 77041 acaggacttt tatgsattac cgattccatt tagatsatOg gtttaccacc gggacaggac 77101 caaaacattc tagatgacga acatttcata ccacacacta cacatattsa gctagtagta 77161 tttatatatt caggoagtat agtaatatta acgtaggtac astattagag tgttacagga À. 77221 cagcattatc gcacacagtc ggaatttttt cttgagtttt caggeagata tcattatagg 77281 tctagsaaaa tagtttagtc actatcatat tcatcatsac tsactgtact gtaatatcat 77341 tcatagacat agtatatcgg attcaegagt aegggtatta tcaaacatag astesaaata À,.. 77401 gttctataca tcatgttsat ttagatattt cttatggaca cgatatatat catactsagt 77461 atgtatggLa tttatttatc aattsatatg cgtatgtagt aactactaca gagtttatsa À, ' 77521 gatcatcatg tcatacastt ttatttattt gacgtagtgt ttatatcatt ttatgttttg 77581 ggataataat tttatataat ateaasttat atattasttc tttttatata ttgsagtgat 77641 ttsattsaeg aaastatgta atatttatat aattaggttt ttccttatct astsatagsa 77701 ctgtatacat ggtgatattc ctacttgatt taegtgacct astatsatta tttagatatt 77761 tacatgtttt tcgoataaat atsattcata aaastattat tattsagata ttsatatata 77821 ttatccatga teatatatag agsaacatta tattsatagc castcgeata tgsatsacat 77881 acatagteat aatsaegata goagttaatg gosaactsat attattcatg ateactgata 77941 tsaaagsaga teatatagoa agatatattg aagtgtatat catatcttat tttatggata 78001 aacatttaac ggosacttat aagttactta ttttttggtt tattaaacta ttggtttttt 78061 cgtacttttc ttccastttt tttgtatttt tatttsattt tsatatatca ttatcatgea 78121 tgtagtatag tattttactt atacactcag agsagsagac gcttcgtatc tgatattcat 78181 tatcageacc ttttttaagc ctagtgcast aggagttaga aagataggag ttsagtatat 78241 tggsaaastt aagtgoasta ctaggaaaaa cocaacagat astatgagOc acgagataga 78301 tatgoacata tgttcataca agttagtatt tataggoact atttgatgat astcagattt 78361 ctsaaaeggc tttattatag atacagtttt tatagttcaa tgtttttatg agttttttag 78421 atgactatag tctacaccac tgactsaagt tattatttcc aagatcacat attttagtag 78481 catttatata tcagttgtat tttsacatga ttacttatat gttagoatag ttgataaagc 78541 aaaagttatc atctatatgt tteaeggtgt taggtacaaa ctccatattg tastactttc 78601 attcagsata gtattgtttt tacatttttt attatsagga aaaaactggt ttattcattt 78661 tattttsacc atgoatacac astttacagg aactgataca tgtttagtca ttacagcatt 78721 attttcacca agatacatta tttttttaat ttatgtgacc gtagaacagt aegattcaca 78781 tattgactca tcastgacat tacaaggaga tgtagaatta gggsatcaca tgoagatsat 78841 catttgaatg tattgtgtgt atccatatcc tttctcagea tatctgacca aaasttctat 78901 tttactgaca ccagttccat tsacagggct tacttatcta atatctacac atgtagttac 78961 tasttcacaa gagggttcgt ataaatsaac agtagtatta tcattactag atgtatgggt 79021 atagtataat acagctgcat gatagtactg aaaacatgtt agtaacacaa gtatatgtgt 79081 aacgtacata atagsaaaaa gtatsattta tgacttattt ttacattata gttsaaacca 79141 tsaaactatc ttsattacaa ataaaatact atgtagttcc attatttttg atagoattsa 79201 atgaaaggea ctattatatt gtttggtaaa ccaasttgcc cgttatgtaa attttcaaac 79261 gaaatacttt cgsatsaaaa gatagatagt aaatatgsaa tcgttagast aaatatagct 79321 acattattcg atesatcaaa ggtagtagaa atactaggta tggatsagtc ttacgatata 79381 ttsaattata ttggagaaaa attaggaaac gsatatgttc ttgLatttag gtatgatgat 79441 actagtaagc aaatggagta tattccattt aegsastaca tagtsatagg acaastatca 79501 caagattcta tagatttcga taagatgctt astgaattag aaacaacacc ttacaatata 79561 cttattsagg atsagtagat atagtttagt gtactggata tsatattatt aggtttattg 79621 ctsaagacag tatctsacat atcagtattg gattcattca aaagatggtc tatacattgg 79681 tatgttactt ttatttttat atccttgtta gataacactt ttttagatsa catgtaagta 79741 aagtagtata agtsatcttt accaaaaatc agaacastag attatttggg tatatcttat 79801 gttttsatac catatgggta ttatgtatat ctatatatag atggastata cttgagttta 79861 gagtaagata tagtattatt atcggagttg tattttattt catttccatt aataactatt 79921 atacatatac cttagttagg aegtttatsa ctaegtttsa ttgttttagt aaatttgact 79981 aactttatgg ttacgagttc cttaagtatg ttgtatggat aagatasttc tatttatttt 80041 aastacgtat cacagtttaa tgatttactt ataagctttg tatttttaga attatsatac 80101 ttagttasta cctttactat gtatacgttg aaagasttac ataacgatat aastttttcc 80161 atatatgctt catcaccact gtatsaatac tttsatagat tatsagatat aagggttata 80221 astgacatta ttattagtta tattatttat actattattg ttattatgtt atttttttag 80281 ttttsaacga actsataaaa tggsasttgg gatsaatcat attaageaaa ttccatggag 80341 tgatsacgag catatatttg tatcatattt atttactaat aaggacaast atctcacagg 80401 tcatatgagg ttaacatata gacacgatag taaaacagca gttttagatt ttesaggtac :.,.. 80461 caactatacc tattatctag acaattttga tgatgttagg aaattagtac ctaegttgat À À 80521 actgagtsaa tagtatattt astsatactt gatttatttt caastacatt tacagatttt 80581 tacagaaacc ttacgeagsa tagaggtttt aggtgtcatt catsacatat astgoactac À.'. 80641 taaatcatcc atactatgaa tgatacaaca ctgttttsat tatataccat ctatatagtg 80701 geatgotagt aaactatata aaaaactatc agtatataca aacgactggc attagcacat À 80761 gcaatagaca tsatatatac coggaggatg tsatatccat ttsagacata tactcatgsa 80821 atttatatac tttctatata ctttacaatt ataggacgga gatgagtagt ctacaccact À 80881 atcagattca acatattttt tagsacatac actcatttta ttagttgact cggtagggag 80941 gtccgtgatt ttsatacttc tttttcttat atagsatgaa tastatacOt gatcatcoga 81001 gtagagttat tcttcatagg tastacttaa aagattcttt atteacacct caacagatat À . 81061 atatatatgt ctgttattag tagagactgt atagtatata tcatatttag gttatgtttc 81121 atttaeBtag tattatagaa aaacatgact ggttatgtta atsataccat caggagataa 81181 tagagtataa ttacastgtc tattatagat agattgttta gacatattat cagtsagtsa 81241 gatacastac catttatcag caggtagtac atgatastca ccagttcagc atattttatt 81301 aatgctacaa ttacaastga ctttcaaaac tacttattag tgttgagtat tsagatatat 81361 acaastacta acgtttagta ttatgttsac aaastataca tcatgagtat tesastatgc 81421 agtattcatg tatttaccac ttcagtacat acagtgtaaa tatatggatg gtttgttatt 81481 atggttttca ggsacttata ctatggtatc atagtattag tattgosagt tttattcatt 81541 ctatcatatc atagsaagta ttsastattt tatagaeggc aagttaccat atcatattac 81601 acagtatact aaacatgsac tgatsaaast tattatatta cgacatacca ttttsaegat 81661 tgaegoatat acaaasttag aacgsatgaa agsaaactac ttcttatttt aactOtactt 81721 aaatgattca actsastaat ggtataegta tatttgttsa tcattatatg aaaaaagata 81781 tatatatagg tatttcagat tttgggttag aaaaagatat aaaegatgga attataggga 81841 tagagoattt actageacac atattsatat cattagataa caagtatttt astgateaeg 81901 ccagtacttc gagtacgtat atgagtttat ggtgtgttgc tttacaaaeg cgtcattatg 81961 aegatgatat tagsacagat atsagatggt tttttgataa aaagtatata ctsaaaacag 82021 atttttatag aattgtatta gsaasttata ttacagaact agsaastgaa tactattatc 82081 gtacagsaat gtatcattgt atggatgtat tggagtatat atatggagga gatatttata 82141 acggaggacg tatsactatg ttagaseggt tgacagasst acgtastatg ttaagtsacc 82201 gsatgaaatt tatatcaggt aagsacatag ttatatttgt taaaagacta actasteaca 82261 tactsaegtt actsacaaac acattaggta gtataccaaa gtatcatatt ateatacatc 82321 tagatcatca gattcaggat gataggagsa agattatcat gatgacttgc cagttttata 82381 ctcttattat ccaagtagat aatacaatga atsatttact agatattatc tgtttagtag 82441 aaaactatsa ccttatagac tatgsaacaa teagagatsa attatatOtg tgtatttcat 82501 tcgctsacga ggatcastac gaatatcttt tgtatsacat aaaggatatg gattttsaca 82561 taastagsat agsactagat ctaggagagg attatattat gastatatat atcaactttc 82621 cttggctgsa gastgatata ttagsatata tacataccat gsataccaaa agagagatgc 82681 tgttagccga tttaaagaaa aatatgcata acagtatact agsacataag tttatgatta 82741 tatatcctag ttttacgsag ctattatata atataaccga taaacaaaat cacggtatat 82801 tagttntagg aqatattsat tttacaccaa aaaaao;'taaotatra ra--- 86161 agagggatgc ctggatgacc aatactagoa ttcaccagtt tattatcacc atgtgttaeg 86221 gtacggaagt astttatata ggacagttta attttaactt catgaataga cacgctattt 86281 acgsaaaatc atccgtgttt aacaaaasta cggaegtgtt tesattesaa gataggataa 86341 gggataacag atcatcaaga tttattatgt ttggattatg ctatttacat cattggsast 86401 gtgctatata cgataagsat agagacttta tatgttttta tgattcagga ggtsatsatc 86461 ctaacaaott tsaccattat aaaaacttct tathttatea taattcaaar aaactaaaca 89821 tatatccagc gsagtagaac atctatcgaa gsaagatcct cagatggtta aagctgtact 89881 agttgattat atatttttag aaaatgaggt astgtgtaaa ataagcttta gattgaaaaa I 89941 gcttattatg gaaaaagttt gtaggaaaac tctgatagat acteacggag aagtsatcag 90001 cgtcgtsacc tccggagacg atgatataga ggatgaatcg ggagagtttg aatatgsatc 90061 agacggtgta tctggaattt tagaagsaag atatgatggt aacaggagag gtggttacaa 90121astaaasqaa acaaatoaet atoatoaara aa -- ,,_--. -^-- 93481 tgaggtagat agagcggtta aatatttcat atcggttata aagaaatata taaaactsaa 93541 agsatctacg ttatatgtag tagttaagga tacaacatta tttacatata astacgataa 93601 aggagsacta actccagtag atastactta ttatacattc agtsaagaac tagatagoac 93661 ggactatact tcctcagaaa taacttctat ttgttttact attactgacg atatgagtat 93721 ttctgtaaag ccaaaaacgg gttacattgt taaagttaga tctgatsatt ctaggtatta 93781 ctaaattagt ttttttactt tttttatatc tatacatatt tataaettea acactaaatt 97141 ggaaggtaga atatcaaaaa astcaataca ggatcatgat ttgtattaga astsatsaca 97201 gacaagtttt ccastgtttc astattcast agatacagat ttggagatgt tgcaggsatt 97261 tgtaacgtgg ccatattsac aggsastaaa gttccatagt atagaccctg caggtccagt 97321 ttaccaaaga taggtttgta atcacagact cgtataagat atttagatag ttctatatgc 97381 ttagoatcat ctatatagea actacacgta aggctgtgga ttataggatt aaaegttgta 97441 tttttsaaga agsataatat attatatatt ggsatgatag taagosatsa gsaacttatt 97501 aactgatcaa cgggtaatat agaaastttc ttesagtaat cgtttagatt aacagtagsa 97561 atatggttca astactgtat atttatttta ggagtatatt gcggaggagg acattgatga 97621 agacatagoa tgaactcaaa tttgtttsat agacatsatg ttataggata atagcttatt 97681 atatctagtt tttcatactg ggtgttccat astgatgttt caggtatcca tccatsagoa 97741 tsatagtgat acaaaaacgt attattsagt atagggggta aattcatacg attsaacgtc 97801 ttttgatcat ctgtgcgttc atgagagttt cctatsatat ctattatacc acgattagag 97861 ttagtcatsa ttgcogttga ttatttgtsa tateaatttt ttatcatttt tagataaatg 97921 tttagtattg tctagatatt cattsacata atatatgttt tattgtagea actgtttaaa 97981 tsatatsata atagctactt taaaatgatt aateattgta cgoacaactg atttsagtat 98041 agatttatca ttacaggttg catsaactat aaaagaagta aagttttgta aacaactaga 98101 tcacgttatg attttaegga ttatatcatc cttatagttt tctattatta acactsacga 98161 tgatasttta gastcaegat agtatttcaa aagactttta ctsastsaeg aaaaaacaat 98221 agagggtgaa ttsagatcta astcagatag tttttttagc tatcatttat aastgactat 98281 gggattatcc tcatttsagt atsastsagt attatactat tttatagoat attctgtatc 98341 tttattatat atatgacaaa gttttttatt ttatsacgct agcaegtata cattttgtgt 98401 ttggtatatc atttgagaaa catatgtaga atttattttc atatcatcaa atatatttac 98461 teaegtagag tatgttatga atatagattc tatgtatatt cttatatcaa acttttcagg 98521 gtctatttta gosatcacgt tsaacaastc gtagtagsat ctattagagg atgtaastgt 98581 tttatcatct atesagttat catgatsaaa atcaacaaaa tatgatttcc aggtttcatc 98641 cctttcgtat atastagaaa ggatatcacc tggtatacca tatattsatt ccaacataaa 98701 tttcttsatt tagctatcgc tatccaacat atatacaact tttaacatat tcttatteac À.. 98761 acgagattgt ttsatttatg agtagatata acttsatacc ttttagtsaa tagtgatagc 98821 gggttcattc gtatatactt tatcatcatt atagattatt tatttcatsa acaaccaata À À 98881 actcgtagta ctattttttg gsastacaaa ttatttaast gtttotgtca ttatactgat 98941 gactacaggt caegttttat gtastatagt atacagatag tgactatcat tatcatcaaa 99001 tttcatccat gtatccattt ttagagaata ggaccatatt agsagtagta acacacttat À. . 99061 cctgtatact ttgatsastc tagtttcatt aaagagtttg gsatatatta tatctsagtc 99121 tttastaggc tcattcaagt gsastsaagg atttsactca gtactsaegt tsacgettat À 99181 astatcttga aagtsaggtg aaagttttgt tacgsatsag aaaegtttgt catccaggag 99241 tgtattagac tgttgtttat aaatatcaat aaastatgta aaagatgtat agttttttac 99301 tsactggttt aggtataaaa gagttacatc gsaagaegac ttaegeacta tatagtatgt À . 99361 ttcacagtct cttatgsast gosaaaatat ataaaasttg gtattattaa aastgtcatt 99421 agtcagoact gatttatgat actttttsat aatatagtta atagataega cgtgattsag À. 99481 acaaaagttt gatatattat cogatagttc ttgagtsaag aasttsatat tgttttatac 99541 agtatatata agatatttcc ttattatsaa atccatacta atactatatt atattsatag 99601 atatttatsa astgtttaaa tgatatatat tatsaegata aacaacagta acttsatgac 99661 atattttact atatctttat atttatattt asttattact gttatgaaag tgatgteata 99721 ttatttttta ttsaegsagt actsattgta gagtccaaat catatattag atattgcata 99781 gcatattata tggoatgtsa cagtesattc ttttatatgt ctttgatcac actttgtttt 99841 aacggtacta tagtaggata gaaacaagtt astataggta taccagtsac acatactaga 99901 tcatsatata cgesacttcc gttcactaac aaccatgtat tttcatcatc tgtatacatg 99961 aastatttca atacaccaca tgtatsatgt tcatcaggat atsacttast agatgastta 100021 tttactacgt ctsacagaca goatttttca tcactatatt tatagsatat ttcatatacg 100081 tcttagtatg atsatgtgtt gatgagsaca tctatagtag tatgtactat agattattat 100141 agthatsata ttttttcttt atatgcttag tsagatattt ctagsacttc actatccact 100201 actacgtcag atatgattat tccatcattc gttaacgoac tagatsatat atttatagoa 100261 ttaggtaaeg accagtatat atattccata agacttgtat aatatttata tagattttag 100321 agtttatcag aaagttattt atccacatat tagttagtac ttttattatc atatttaaaa 100381 tcaaatacat aeggaggttt atatsatacc tcagattata tccacgtatc catataatgt 100441 attsatatat tagatatgoa agattcatat ttaggatggg tatsaggsac atgatttagg 100501 ttacteatat atccgosata gtgtccagga tatagttcat ctggacatac gtgagaacag 100561 cagtatatsa cattatcagc ggttgtatta ggatsacagt atttattata atcatcagat 100621 tgtatagagc agtgatatat agaagtgatt gttacaaaac atagacactc atacttattt 100681 atagttatag gtattgtsaa catgggacat ttcaacatca ttsatttagt ctttagatat 100741 agttatgaca tacattatcc tcattcaata tgtttaaaag tatatttatt acagtatcca 100801 taatagttag tcattgactg tatatatcat aaaacagata ttatatattc cgatttatsa 100861 gteageatat tagatctaga cgtacacggt astacaacca gtsagatact actgtacgtt 100921 ctsaattgtt tatccgoatc caaccaaast ctatcagggt cgtcgtatgc catacctaga 100981 tttcatacag aaaattcaac atccasttag tsagggastt ttaaattagc tttttatata 101041 ttatagatat ccacagtatt aggatagtac ttttctgtea ctagtsattc actacataca 101101 tctacctata acaaaaaatc aaaautccaa acttatactt tcccatsata tcatatacaa 104461 atgastatat cggtatgtgc attatagtta ttattgtcag taagaacact ataattcaca 104521 acagtaactt tgtatactgt aatattcata catttattac ctgtatatgt astactagac 104581 acgatgggta aageacaagt aagtttatta tcagatgttt tacatattag atactgsaca 104641 tcttattttg ataatgatag tgcactagct actatacaeg atgtaacttt tattctagag 104701 ctagtattat cgactatttt aggcttttta ggagoataaa tagatacatc tastacatat 104761 gtatsattat actgatatct agtatgatat ttatatatca ateattcaca tothtt^A 108121 ataagtccag aetatgtatc caataactta attaaaggat ctttaggact ttagatacag 108181 gsaaacaegt agaatacatc tttaacagta tctatasttc cagttatagc agtsacggac 108241 attccagcta tcatsagttt tggacatcac gacaaacaeg ctgatgtcag agtagttcat 108301 agagttgata agctcatogt aactgactag aatacatttt cttatttagt catagsatat 108361 tttctttgta tsaccgattg catggcttga tgttgagccg cttgctgtcc ggacattsac 108421 atggoacctc caaaaatsag agatttatca aaaastoaaa atatththtt al. __. log..DTD: 111781 agtttaatta aatagagtat ggttgtastt atttactaat aaateattga tatactatsa 111841 atcatgtttg atatcactaa tatgatagea ttataegagt ctsacgatta tgtatcaggc 111901 gactacaagc attctcagct tcagaaagat tttttsaaac tacagataac agaagttgta 111961 atgttagtta aatctggatt ctatccatct aaattatcta aaaagttcta caagacasta 112021 gctsaattat gtgttgataa gatatattta tttaaacatg astacgtatc gttsaaagac 112081 ttatttacag tsatttatac attcgatgac ttaegcaaat atsaaaaaat tataaaatat al 115441 caasttagat astgcacatg tattaateaa tatcaattgc ggagattgac gttgctgatg 115501 aggcgatgtt tgttgoatat aacattttgg tgctgsatcc gaagaactsa tagggcaagg 115561 tgattggggc ttatatactt tcagtacgoa actagtttct tgtttcatgc astatatagt 115621 tctcacattg catagtttta tagattttag aactaaatat cttcattcat cagtgtttag 115681 astgsaagga ctaacaaagt attttggatc gtgaaatggg gttccagoac tttattccat 115741 ttatagtatg astatttctt cttattatat tuacaaaaac atataaotca Oat^^^^^^ no 119101 gtataccast tcgttaaata gtttattttg tccatagtag gtatctagag goastacatc 119161 ctttggsaaa ttaggttcta caasttttag tattatcatg tatgatctat atcttgtatc 119221 gtsatcgttt acacaaaata ctcctatgtt tgttttatta acagaggosa acatatttac 119281 agtsaaaaga tcagagastg gtaattctat astcccatat ttattacata cagosacagg 119341 agtagatcca gsaggacaeg tcaacacaaa actagtaast cctatactcc cggeaaacaa 119401 gtatatttat acgtatattt ttataacacg attttcacso aatoaaetat ratraor^ 122761 tttatgtsac gattctgatt tagtatcagt tgattgtttg ttctagactg agttttgtgc 122821 agsatgatac ataggtaaat ttttcataca tgtttttgaa tccgttttat gtatatatat 122881 gaatgoatat atcattatgt atttgtacat tattgtaatttateacatac tatattaaag 122941 ctatsaagtt tttagttcaa ttttgatttt ttgtatattt atatacatsa cttaaagaag 123001 tsagttatta acatttttgc acattsaaaa tagcattcat catattttac agtaataaaa 123061 tsacatacat tactattsat tcgtttcaaa aatgggeaat atttttaegc ctattccaaa _. . . 126421 aactattacc taaaacatct agtsagacaa attctactag ttgtataast attcatatag 126481 atagtattcc tttgaatttt ctggatgatg gtsatsasta tttcaatgtt tcogsagtga 126541 gtatacttca ggtaagtcat ggaaatgata tgatgaacat agatsastat gtcgatggta 126601 gctttgatta catagcagta ttatgtttaa aaasttctgg tagatatgtg attatgttsa 126661 atcattgoaa caaacaacac gtsatgosag ataatttctg cttastattc agatctttat 126721 atggtataaa catattgact caastsattq qaaastatatatatttatta atteaattaP 130081 tattacatat ttgtattcta aacttgttat gtatatccta catacttttg gatattttca 130141 tgcgttatta tatattatac tataccttaa cagtattatt acttatttta ttsagatagt 130201 aaastsacgt catctttttt ttataataaa tagtasttat gtatagsata aaaatactaa 130261 taggtatsac aggtagagta gatgaggtta agttacatga cctgataaaa gasttsaegc 130321 gtttggsaaa catagaatta agaatagtag ctacagsaaa ttatatgaag ttcacagacc 130381 aaaaaactat aggtattcct atttatacag atsasqacqa atqqactaca touaaaaaaa 7+ 133741 cggataaaat cggtagtaat ataagagcta cagattgacg atgtaaaagt aaacagtata 133801 taatagtatc taccaccaaa gsagsagaga agtgttttcc tcctaatact cagtgOttgg

133861 aacaagatat aaaagaaaaa astttaaaaa taccgaagtg cgtatactat cctsacaega 133921 taggagatcc taaaggattt ggttataagt agtttttsaa acactagaaa ttattagsat 133981 acagattaca agtaatgtta tgcttttsat agttttgaaa tatatatgta atsaagosaa 134041 attsaacata ttatatsata atacattact cacattacat asetactata actttacata 137401 cgcatttttg atatatgcta tttatsatgc tatctctatt agaggagtta tatatatatt 137461 tagctatagc tactataccg gctattgctt tatcgtctsa gtagtatttt aacagtgttt 137521 ctattaaaga tttagacacc atgttsaaaa tcctcgattg tttatggtat tccatttesa 137581 tcaaatattt ttaaaaatat aaaagtaatt tattacaact agttsatatc actaaaaega 137641 catatagtag taggttacat attatcatta aggctcatca tgtatgacat acgtttatta 137701 tsatctagac gagtgtgtag ttastatttt tattctttag acataqasaa aacteatacc 141061 ataaacttat acgtataaga ttctsactct actattgosa gaagttatat catctsatat 141121 catsacatca ttccagaaac attcttttat atgtatattt gtacastact tagcatgtcc 141181 tggsatagta ttaggtttta teatagtatc gttsaaatcg tacttataga aagtaaataa 141241 ctgacgatgt ttattactat cttcaaaagg attttccagt atccaacgtt gggttttatc 141301 atcccatatc gtcattttca ttagtatact acacgtagtc cgcgttatag aagtttgtga 141361 agagtcgtac ggacacactt tcasteaaag ataaaauttc ttcatqanqa ataastaaca 144721 tgttgcggta gcggoatast cggtcttttc tttgggattt aastattttc tagtatcatg 144781 atatattggt aactttcttc tacaaaattc tgatcgagtt atcgcaacaa aastsataag 144841 tatagtsatt atatccataa taactatgtt astsacattt tagttcattt attatsagtt 144901 tgttaacgaa ctgacgttat gtctcattaa tatagtactt atattcatgt cgaattcata 144961 catcasttct tctaacactt ctttsaaagc gagtsataac attatatctt ctacatagtg 145021 tatastactt tttgttatsa gaggtattac ggtggcttct atacaggtsa ctactggttc 148381 ccttacttat acgcctsata ctgatttact cggagtagcc acgacagaaa cagtacgtcc 148441 tccatattat ttataagcgt ttattcogtc tttaaaacac gatattatgt ttttatgttg 148501 tttgttattt aactcgatat gatttaacag tctatataat ttatccaaat cttattagsa 148561 tatatggtsa ctatgtttat tatttgttat caegctcttt atggattcta tttttgtaaa 148621 agctatgtsa tatagactcg ctgaaacgat attcatacca tctaatatag goacaggsat 148681 atcgagtata tttastacat ctttaggtaa tatatttgat gaaatttatg goatgtatgt 152041 agactccaaa aateaastat ttgacgagta cgctacaggt agaagtatta aaacatgaga 152101 tcctttaaca aaaactatat ctggttctac attatgtgat aatatattsa cgagattatg 152161 tctggacgaa aaatatggag tagatagaac tatgtgtaac gastggatgg gatatgatat 152221 tsatagacac gatatttcca ttccgsaatc aattaacgat agatatacga agatatgatc 152281 caegggagac aatastatag tatgtgeaga ttggttgoat cattteagsa ttataggagg 152341 aaaaaaaaat astennatta tsaacaacat attaatacaa caaacacata aetttaaaaa 155701 ttcaataast agtctgctgg atagaactat gttaaaatgt gsagaagatg gatctttgat 155761 gatttcgaga cattccggta tctattaggc cttgagttta gatggttcac cggtaeggat 155821 ttccgattgt agtttgcttt tatcgtcaat aaatggcgoa tcctcatcaa catatcctta 155881 ctctattttt aacagaegat aacggatttt attcttatct atcagaaaaa agtgatgatg 155941 aagatattga agacatsaat actattaaga aatatatgga ctttattata agagttatta 1 RnDl tacathetaa aaaaaaacta aaaastatsa aatattctta cgagactatg agtgastagt 159361 ttcaagaett tactaatatc attttcggta gacaacattc tttgoatagg tataacgtta 159421 tatcgtattc tgtaagsaaa acagaagaag ataccattsa aataccacca ggtatcgata 159481 attcacaaaa tgcggatttt gatggagatg aagastggac tatagtagsa caaaatccaa 159541 aaagcgtgat agaacaaagt attctsatgt atccaactac tctattaaaa cacgatgtac 159601 acggsatgac cgtataeggt tctatacaag acgagatctt agctgattac aatctatttc rq1 ntaaatacaa tataacacaa aacaaaotac ttaatatatt aaaaaaqtac aqattqqast 163021 tagaagagga gatggagatg gatggatgat aaaaaaggcg gggaagtaeg atcctgctgc 163081 tgagoagtat tgtgatttta tactggacag atataaagat acastcacat gaggtgacca 163141 aatgtttsat agcctagggt atagcggtta tttcgsatct gggoactggt gtcagacatt 163201 tatagattta gttaaatsac tatgatgtta atsagoattc tsacttcaat aacagtttta 163261 tagtaaacat cactcaagat tacttacttc tattttastg tatagattaa aeggttattt C 3q ^. -A-A -at A^ AArAAttaat ttaacactat tatauttata astqtattac 166681 tcctttaccg tatcatcttt tatatacgcc tttatcttag gcactaactc tastastaca 166741 gattccttgt tatccattta atgtatagsa ctsatttata atsaacatag taastatggg 166801 tsacttctta atagccataa ttsaasttga aaaaaaaata tcattataaa acgtaaacga 166861 acaaaaaaca ttaatttsaa tttgacaata acaaaccaat atgtattgga caaattctga 166921 agataaatag tttsaaacaa tagatgagat tsaagccaag gtaaaggagg atagoagtca 1669R1 tcatatttcc aactatactt ctqatacaga accggaastg attcoggaag tagtsaaaaa 170341 cgttastgtt atatatagat atatgtctag tgsacccata gtatttaacg ataaeggttc 170401 gttattggaa tataaaagat acagtsatga teagggtttt cctaaagaat tatatacagg 170461 gaaattagat ctcaacggsa gcgttgasta tatsastaac atatattgta tagaasttsa 170521 acacattaat ccatgtacag gtattactaa tcttgtatta cctatsaaat tcatagcaga 170581 attctctcat aacgatgsat tsatacaacc cagsatagat aaaactatga aatatctata 170641 toaaaacaaa tactacaaaa atcaactatc cattattata astcatttua acastcaaaa as 174001 agactgtsat catatgtttt gtattaactg tattaaaaca tggatgacta ctattsattc 174061 taageagcaa tgacatgast gcagagtacc ttatsagtat atcatacaaa gtcctatatg 3 174121 gacagtggat aaggttagta agaatcagtt aagtgtttcg tacaagactg tatatataaa 174181 atcatgttaa cgttttgtag aagttgaaaa aataatatac tgatacaaaa tggattttca i 174241 agaactttgt tgtagtaatt tgttaaastt cgagaactgt tcactactag aaacgoataa 174301 aaaastatat ataaaaaaaa atathtatac caaaaaotat acattuataa atatattatc 177661 gacagatgat ttgtaaggaa tagattacac cgatctasta aaastsatta tateattatc 177721 tttcaacata aaaaggactt gtttactttc aaatacttta aactacatat aagsaaagta 177781 tgoatagaac tatttaatta tagagagagc cateatttat ttttsattat ttaegsacct 177841 actaataast ctatastccg attcaagaat atgattgsaa ataacgaaca tatagsacta 177901 aaagataaca actttsaaat aacagatact agatataccg ttataaetat attsaaggat 177961 ataaatsaaa tattttcaga tsactsatat aacttttcgt accgtgtaaa ttgcatsatt g7 181321 aacagtaaga tataccattt ttaacastat aaagttattt gtasttacta taggattgtt 181381 atgtagtgta ttattattac gtastatagt gtacttgtac aatagsatat tacagttsat 181441 asttgattaa ataaaegsaa ttaccatgat tttaastgta taagttatsa acatattsat 181501 agtsasttct gttatataca gcataattat ttagaactaa tsaagatgag agataattat 181561 tttataaatg ccatacattt atgtttatca ggaggaaagg atttttctac gtggttatca 181621 ttatatacac ctaqqtgtat actaqatacq ttaqctsaaa caatattcaa tggaacgtag 184981 tsatccacat actgaaagta gtaaaastgt gatatatgat aggttcaaaa agttatatca 185041 cattataaca ttcagaaaat ctesataetc asttaattat tatsaccatt aatagatatt 185101 attttgaata tattcaaaaa cagacataca tcatgtasta taacactata taatacattt 185161 acaccacgoa actacatata ttgctttgta tatgttgtat gaaaggteat tacgtsaaca 185221 tsataggtcg ccttacteac gatccteaaa gaagttatag cttcacatga tatagatata 185281 aaactaggta atatatacac actaaaaant ttttatacat tacaateeat attatneata

I

188641 gttactacac ctaactggag gatatatact atatttatac tccgacattt actttacgta 188701 asttsaacaa atatttatgt tatgatttta gttgctaagt aaggLagata gtattgagoa 188761 tacactaaaa tacaacaatt tctagsasta aggttcatag cttcttagtg ggacaataaa 188821 tcatcttcaa acataacagt atgatgcatc agttgatgtt gctttatatc goatagtttc 188881 ttagtggatt cttctttcaa ccastcgtag aacattcagt cgtcatttcc atgttcttta 188941 tsatattgat tattcatcac tctcattaat cttgactctc ttgactqttt actataaata To 192301 atctacagoa ttttctttat agttaatgtt gtasttatag gttatacatt gaacaattga 192361 tatsagtgtt gttttgtgct tttcatattc ttccacaaat atgtttttat acatttcaeg 192421 gttatttgat atatcactta tcaatccatg aatgttatta acatttcttt tetttaastc 192481 ttatacggaa actttagtct taaatgatgc cattatttca ctaaaangaa cgtgtaagag 192541 ttcgttagta agtatttcag aatacactat actagagagt ttagaaasta tgttaacaaa 192601 ttgtgttgtt ttgacacanc taqtttqaaa taaaatasta ttaaoteata cattthtaaa al 195961 ttaastttsa tactcaaatt caattgatac aggaaaaatt aggatatgaa cattatagtt 196021 attatsatat agaatttgaa cactattata ctacagtatg tttgatacta caaagtsaaa 196081 gsaacatgga aaaggaagat catgsactat ttgacataeg agaaatgtat catatactaa 196141 astcattgtc tgagattact tataagctgt atgttttata tataaaatat aaatttgttc 196201 aatggagtat aagttcttca goagttgtaa ctcaattagt teatactgta ttgattacag 196261 tatataatat tgttactsaa tttataactn aaaataaaac chtcaast= AAArrAarr 9z 199621 tsattatatt caaagtaaca atatacaaca gactccttat ttatcagatg tatttgatga 199681 tastsaacgg gttcatttac tcgsacaaga asttgcagaa cttagtaaaa agaaaactaa 199741 aegoaaaaac ttgttagatt ttacaaacac cctttttast aagaacactc ttagsatagg 199801 aattctcaat aaacgcgata taatactsaa ctatgoatat atgaacaatt ctcagatgac 199861 gatggsagat ctcgsagatt gagaegacga agagatagaa aatatgtata tttatataaa 199921 acaatatcac gsagttcata aaaaaaaott aatcattact antatatt "hat - 203281 gacgacagca ttaagagtat agagattcat acgtgagtgg catcagatcc attatttaag 203341 tgcaaagcta tacagtaegc tattattsat gacggtaccg gtacaaaaat cgoagsaaga 203401 atastsaata tcaatgccac caaagagttt gtattaatag cgaataccaa cataetaagc 203461 gacaacaaag attttatatc attgttgtta attatattag agtatagtag ttatactcca 203521 tcaastcctc cattaccgag tcatttattt ggtaaaaacg ataattgttg ttattctgtg 203581 aaaagttcat tttctttgat accaqctcac acatcoaact chtosaaa arraa^..

206941 caataatgat tatatgctcc gtagatatag gtattaaaaa tccagactat gacatattta 207001 attacgataa cactagtsat actattaaac taatagccat tgaaaaatat gattggacca 207061 agsactggga gcgtagtgta gcgagagatc ttactagata tsatccagac gtggttatat 207121 tagagsaaca ggggttcaaa tatccaaact caaaaataat atattttatc aaaggttttt 207181 tttatsatag teatacgaag gtgatcgtga gsaatcctac ttttaaeggg ggtagttaca 207241 gaaacagsaa aaaacaatat attuacatat ttatacaaaa aaraa a--.- 210601 ctacattagt aggtattaat catsattatg gacctagagc catattgggc tgagcgoaag 210661 ccaaacaagc catatcttgt ttgagttcag atcttagsaa taaastagac aacggaatac 210721 acctgctata tccggaacgc catattgtat tsagtaaggc cactgaaaca tccaaaatag 210781 ctattasttg cttcggacag cacgtcttag ttgatctcat gtcctataaa ggaatgaatc 210841 aagsagatgg tatagtagtc aagagagaat ttatagsacg cggtggactg gatattgtaa 210901 cggataaaaa acatcasata aaattta tPOaaaabEE haaaaama -,.^ qua 214261 agacatcaga agatttacag tcatcgggag gsacaagatc atatgaatat aatttsacac 214321 caccagagga tttaacttcg catattgtat agaatggatg ttagteagta gttatcagat 214381 cgtctggact attaccttct tcttcaggat ttccgataga aatagoaaat gtatcaastt 214441 tcacgattac tggggatggg aacttsactt ggggagttat cgtattaacc tcatgatata 214501 catatttttt gatgtctggc aagsatctta gatagsatat taccttatca ttagtttcag 214561 tggctattag atcqtcatac ctataacaca atcathtrAa a"ta^ ^,,,..

I

217921 cttgttatca tagcttasta tggtatgaag ctgatctttc atatgagaga attggattaa 217981 caatatagag gtatcaggtt tttgttcgat aaeggattta tctgatgtat catagcatat 218041 acgtatatcc ttatttgcaa atacagtatt ttatataata tagacatttt tacctctaga 218101 tgcagoacgc atgacagata gtgattttat tatctgatta gtagagacca gtgacataga 218161 cctagtaata ttttcgatat cggoatcaga tacattgcaa caacatagat gtgtsatgat 218221 tgatctacaa ttagacggta cgtntctata tqtttuacat aacateacaa taeacatcrt i 221581 tacgatttta catttactga tttgagtgtt atcaaatcag agaatgttaa aacggtactc 221641 tctsaagttc atacgagtat gaastcgtac tacaacaetg atacgtatat tcatgtcgac 221701 gttaaggtga tttaeggsac agtsacaata taaaaagtgt ggagggagat caggggggaa 221761 tagagctggc tcgctaactg ccatattagc ttatgtaatc atgcttgatt gccttagacg 221821 ccattgtact tgatatattt cgctgatatc atttatagga atcggoatca agagoaggat 221881 catsaaccat aaaaaaaaat atttatta&a aacaaacatc anecctta cacacteeat 9q 225241 agattagatg tatggsatac astaaagtag gagattctat gtatttacat cogtgggtsa 225301 ctatcgttat gtgctttata ggatttgtea taccgtttgc tatgatggat ataagatatt 225361 cagctgtatg ttataccgtg ttatctggta tatatsaatc tactagatat tatagsacat 225421 gtaaactggt agattgtata ctaacagsat ttgtcatttg ttttttacct tatcacgoat 225481 ctgttatatc ttatatgatt catatastaa cttcaaaaac agtattatgt gaaaatgtat 225541 cttactacca astgttacta catqccacac aqtatttnat aaaactoast tattotatao ) 228901 gsastagatt gtgtagataa aatagsatta aaagagagtg gtgggttgtt ttgtgaaett 228961 aatttatata atagagttat gaagsataaa acatatattg atacatggat gsaggaacaa 229021 aaaatagatt atataggtat acattatttc catggatttg gtattactat ctacaagsac 229081 gtagaatata gatttgagat aatacaaaga ctgggtagag atatggaaaa tatactatca 229141 gsaaaagaaa aatttaatat tactgttatt aaaaaattag ctattaagat actggatata 229201 ttsaaathta tacatantsa aoaothttet caootoata ttaaaotoo aaAAtrt t 1C'1 232561 gatsaaaagt tatgttcgat aatattattt tastagsatg aaatagttat ggagtgacca 232621 tttttgtaga cactaatagt agaaaagaaa ttacattsat catttatatg tsacattctg 232681 atcagsagta tattctataa aacctgcogt cgttactgta aatsatatsa gcacacatgt 232741 gtcagsactg ttaagoagcg tgcctctgta gtttattctg ttacggttga catagatgag 232801 cgcttataca gagatatttt catatgsagt tsatacttac ttcaaaatat cataegttea 232861 tgatatgtat gsagagaaat acqtattccq ttatsastaa taaaaaaaaa tesatatta 10Z 236221 gsaatactcc agctgctaat atatagasta gttatcaaca aatacgatsa tataccgtgt 236281 agaagtatag caggtatgaa ttatasttgg agtttsatag astcaaatcc atacatgtaa 236341 actttctagc taggtacgca atgcagcttt caactataga tatacgagsa gtaccaatat 236401 acagaaegta cttagaasta cttattastc cagctattsa aagacataaa atattaastg 236461 ctgctaaaga cactatgast aatatattgc acaggsaega aaasttttat tggsatatat 236521 taccqqtaqa aatsaaattt aatatthtsa aetachtosa tttnanoar toAtttr^t 239881 aagtaaaagg atacgatgta ttaggcaata ttgtgoatga tatattgtgt aactatgatt 239941 tatataagga aacgacgtta gaattattaa tatcttatta catasttata tcctacatat 240001 atagaggtat agacatttca gatatttaca atagtsatat agsaatatta cttsattata 240061 aacatctttc tgatattaaa gagaaatgtg aaaacgsast agatgttatg aagaacgatg 240121 tsatatgcga cggtatagac atcatagatt tgtgtacagg ctacgatgoa asttatatag 240181 ctaqaasttc catteattta aaaaaathat caaatactaa act-=a t==ttt low 243541 atttatattt tcatacacta ttttagtggt gtctaccagt ctatatttaa cacgtttagt 243601 catatcasta tcttgtaaag aagataaaaa taattgsagt tcatasttcc atgatttaag 243661 aagatgaaca gccgctgcat ctatcatgtc tatttttcca tcatatgaca taacagaaaa 243721 cacatataat aacgtattat cactagaact attsagttta tgataaggat tgttattcac 243781 agtatgtatc atagsactag catttcocat gttsatacaa aegacattat ttatttttat 243841 aattagtesa tttattttaa tgtagatatt aaaattgata taastgaast ataaaactat lo 247201 gtagataacg ttastcaacc ggggcacgat gatacatatc ctatacatat catatgtaag 247261 geacccaata tgctagoaat atcttatatg ctsagatcta tsastcagtg cagcgtgttt 247321 aacacgcttg tsaaaattaa agatatgttt aattacagsa acgtagaaat agataaaata 247381 attttgacaa atagatacaa aaatatacag gatatagatt taaagtatat agatsagaaa 247441 agtsaggacg atattataga aatsaccaaa ttgttatttt cttacggtgc tgatattaat 247501 atggtagaca gacacqqaaa ttctcatata cattacacta ctaaaaat aa"aaa tan 250861 taacaaaagc tgsaagagta ttagaaaaag actattctat ggaacaggat atagatsata 250921 acgaagatat cagtacagat gaastgatag ctgctataga agatgsastt gaegesasta 250981 atagtcgcta tttgtcaata attagcggca taagaaaaca acacgoagaa gatagtatta 251041 atatatataa aattatgctt agtggtgatt catttaatga aatsatagta aaaatsagag 251101 actatataga aacaacggca aaaccagagg tagagaatsa ttacgastag tsacggtttt 251161 aaatastatt atataaaaaa cataaaasta antataatat ^ttAo=^n n"-an^e (A 254521 tagoastata aacgaaaatg gtaaaaatgc tattatcact aggtacasta tacatgtttt 254581 agatcatata gaacgctata cttaatgata tattctggta gagattaaaa ctccattgtt 254641 ttastattat atactatcaa cacaataatc gggtgtgsat aaagattcta astatacgoa 254701 cgtastaaac caaatatact aaastatsaa attatgacgc gggatgataa gatacttcag 254761 atgatcgtga tgsactatat ttattaattg gcaatactta aaaatastgt ttatsacata 254821 tgtsastata ataaacasta atttaqattt ttaaaatoat astaoA=" ,,,,--- 258181 atsaatatat ccttacatca tgttacagoa tsatttcgat tgtagsacta acagteaagg 258241 tattattttg ctaaaactat tacttcagtc gcttgtsaac astacttgag attagttttt 258301 agaaaegtat taccattast gtteatcaca gccatattca ttgtcttctt caagagctat 258361 attacctatt actatattaa atsactcttc gtsagacata ttacatagga tagtttgttt 258421 aacttctata ggcagagtat accagtaggg tgtacccact gacttagtat catsatagat 258481 agaattsatc acctagtgta ttaaatctgt ttttntagqt aaqtcaaast autacttaaa lCY' 261841 cttttacaga atattctggt gagsacgcac ggtagcatea tacagtagoa agtcgctttt 261901 agagtaggta atatcacgag tctccagaac tatctgataa tcaatagagg aagoacgoaa 261961 cagtaacaac aactgtgttc cagagagtat aacgtctagc tcatgoattc gosacatact 262021 tageagggat acaagagaca gtggacgoat ttgcaagtgg cgggacttac cgagttacag 262081 aggsaacatc gtagsaggca tagcggatac astsaccacg cagatatttt ctctacgatc 262141 atatcaacat ctcaatttaa chtt=ar PrPr=. ==,. -_---_'_ llO 265501 ttatataact cgagctctcg ataaaaaagt ttttatataa ctagagatat cgataaaaaa 265561 gattttcgaa atctcgataa aaactttttc tataactcga gatctcgata aaaaagtttt 265621 tctataactc gagotatcga taaaaegttt ttatatsact cgagatctcg ataaaaaaaa 265681 gcttttcgsa atctcgataa aaaagttttt ctataactag agctctcgat aaaaaegttt 265741 ttctatsact cgagctctcg ataaaaaagc ttttcgaast ctagatsaaa actttttata 265801 tsactatagc tatcgataaa aaagtttttc tatsactaga gatatagata aaaaagcttt 265861 tcgsastatc gataaaaact ttttatatna ctagagatat cgatsaaaaa gtttttagat ^^ _____ ___ ___ _____ __ ______! _-, 4-,

ACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGC

TACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTA m GGTATCTGCGCTCTG

CTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCG

GTGGTTTTTTTG m GCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCrrYUT TTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCA IC AG AI IA DC\AA A

AGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAA

____. _. _. __. . _ _ _. . __. __ _. _. _. _. . _ _ _ _. _. _ _ 11z TCATGGTCATAGCTG m CCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAA

GC ATA A A G T GTA A A G C C T GG G GTG C C T A ATGA GT GA G CT A A CT CA C ATTAAT TGC GT TGCGC T C AC T GC C

CGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGG

m GCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAG

CGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACA

TGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGC

TCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTAT

AAAGATACCAGGCG m CCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGA TACCTGTCCGCC m CTCCCTTCGGGAAGCGTGGCGC m CTCATAGCTCACGCTGTAGGTATCTCAGTTC

GGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTA

TCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTA

AC AGG ATTAGC A GA G C GAG GTAT GTAG G C GGTG CTA C AGAGT T CT TG AA GT G GT G GC C TAACTAC G GCT

ACACTAGAAGGACAGTA m GGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAG CTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTG m GCAAGCAGCAGATTACGCGC

AGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACT

CACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATC-l-l-l-lAAATTAAAAATG

A AGTTTTA A ATCA ATCTAA A GTATATATGAGTA AA C TTG GTCTGACAGTTA C C A AT G CTTAATCAGTGAG

GCACCTATCTCAGCGATCTGTCTA m CGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTAC GATA C GG GA GG GCTTA C CATC TGGC C C C AGTG CTGCA ATGATA C C G C GA G. AC C CACG CTC AC CG G CTC CA GA m ATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCT CCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAG m GCGCAACGT TGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCG m GGTATGGCTTCATTCAGCTCCGGTTCCC

AACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGAT

CGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTG

- À. TCATGCCATCCGTAAGATGcICTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATG -e CGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAG

TGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTC

À GATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCG m CTGGGTGAGCAA

AAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTC

ÀÀ: . TTCCllrn]ATToAAGCA m ATCAGGGTTATTGTCTCATGAGCGGATACATA m GAATGTATT À. À TAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTCTAAGAAACC -. ATTATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTC .

Claims (28)

1. A recombinant nucleic acid comprising a viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion being located at a naturally occurring deletion site of said genome, wherein the insertion site is an insertion site selected from table 2, or a homologue thereof.

2. A recombinant nucleic acid according to claim 1, wherein the insertion site is an insertion site selected from deletions 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 20, 22, 23, 24 or 25 of table 2, or a homologue thereof.

3. A recombinant nucleic acid according to claim 1, wherein the insertion site is À an insertion site selected from deletions 2, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 20, 22 or 24 of table 2, or a homologue thereof. À- À

À À À

4. A recombinant nucleic acid according to claim 1, wherein the insertion site is À.

À an insertion site selected from deletions 2, 8, 9, 10, 11, 12, 13, 14, 16, 17, 20, 22 or 24 À . oftable 2, or a homologue thereof. À

A. 20 À.

5. A recombinant nucleic acid according to claim 1, wherein the insertion site is an insertion site selected from deletions 2, 8, 9, 11, 12, 13, 14, 20, 22 or 24 of table 2, or a homologue thereof.

6. A recombinant nucleic acid according to claim 1, wherein the insertion site is an insertion site selected from deletions 8, 9, 11, 12, 13, 20, 22 or 24 of table 2, or a homologue thereof.

7. A recombinant nucleic acid according to claim 1, wherein the insertion site is an insertion site selected from deletions 8, 9, 11, 13, 22 or 24 of table 2, or a homologue thereof r

8. A recombinant nucleic acid according to claim 1, wherein the insertion site is an insertion site selected from deletions 9, 11, 13, 22 or 24 of table 2, or a homologue thereof.

9. A recombinant nucleic acid according to claim 1, wherein the insertion site is an insertion site selected from deletions 9, 11, 13, 22 or 24 of table 2, or a homologue thereof.

10. A recombinant nucleic acid according to any preceding claim, wherein the insertion site is an insertion site of a medium or long deletion.

11. A recombinant nucleic acid according to claim 10, wherein the insertion site is an insertion site of a long deletion. À

À À 15 À. À

À ..

12. A recombinant nucleic acid according to any preceding claim wherein the viral : .. genome is not an FP9 viral genome, and the insertion is located at a site homologous to a naturally occurring FP9 deletion site as defined in any preceding claim.

I: 20

13. A recombinant nucleic acid comprising a viral genome, said viral genome À..

comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion site comprising a deletion of a viral gene, wherein the gene is selected from table 2 or table 3, or a homologue thereof.

14. A recombinant nucleic acid comprising a viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion site comprising a deletion of a viral gene, wherein the gene is selected from table 2 or table 3, or a homologue thereof, but is not FPV054, l is, 219, 220, 221, 222, 241-247, or type A inclusion protein.

15. A recombinant nucleic acid comprising a viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, ll5 said insertion site comprising a deletion of a viral gene, wherein the gene is selected from table 2 or table 3, or a homologue thereof, but is not FPV001, 054, 115, 171, 219, 220, 221, 222, 241 -247, or type A inclusion protein.

16. A recombinant nucleic acid according to any preceding claim wherein the heterologous nucleotide sequence comprises and is capable of supporting expression of an antigen.

17. A recombinant nucleic acid according to claim 16 wherein the antigen is a cancer or disease antigen selected from table 4.

18. A recombinant nucleic acid according to any preceding claim wherein the viral genome is or is derived from a Poxvirus. Àe e.

À À = À À 15

19. A recombinant nucleic acid according to any preceding claim wherein the viral sea. À

À genome is or is derived from a Chordopoxvirus. À À-

À .

20. A recombinant nucleic acid according to any preceding claim wherein the viral genome is or is derived from an Avipox virus.

À : 20 À

21. A recombinant nucleic acid according to any preceding claim wherein the viral genome is or is derived from a Fowlpox virus.

22. A recombinant nucleic acid according to any preceding claim wherein the viral genome is or is derived from a Fowlpox virus stun selected from HP-1, US-FPV, FPV-M or FP9.

23. A recombinant nucleic acid according to any preceding claim wherein the viral genome is or is derived from a Fowlpox virus strain FP9.

24. A recombinant nucleic acid according to any preceding claim wherein the viral genome is or is derived from a virus mentioned in Table 3. tIL

25. A recombinant nucleic acid comprising a viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion being located at a naturally occurring deletion site of said genome. s

26. A recombinant nucleic acid comprising a viral genome, said viral genome comprising an insertion of a heterologous nucleotide sequence into the viral genome, said insertion being located at a naturally occurring mutant insertion site of said genome.

27. A recombinant nucleic acid according to claim 26 wherein said insertion site is selected from table 6.

À À

28. A recombinant poxvirus comprising a nucleic acid molecule according to any À 15 preceding claim. Àe baa *