CN116744896A - 包含肽的组合的护肤组合物 - Google Patents
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- CN116744896A CN116744896A CN202280010735.5A CN202280010735A CN116744896A CN 116744896 A CN116744896 A CN 116744896A CN 202280010735 A CN202280010735 A CN 202280010735A CN 116744896 A CN116744896 A CN 116744896A
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Classifications
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
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Abstract
本发明提供了一种护肤组合物,其包含棕榈酰二肽‑7、乙酰基四肽‑11、其它任选的皮肤成分和皮肤病学可接受的载体的组合。该肽的组合协同地改善细胞ATP水平和/或上调过氧化物酶体增殖物激活受体α和/或甲基固醇单加氧酶1的表达以帮助提供改善的皮肤健康和外观。
Description
技术领域
本公开整体涉及用于改善细胞能量水平和更新细胞外基质的护肤组合物和方法。更具体地,本发明涉及一种协同地调节参与细胞能量产生和细胞外基质修复的某些基因的肽的组合。
背景技术
皮肤是抵抗环境侵害的第一道防线,否则会损害敏感的下层组织和器官,并且皮肤在人的身体外观中起关键作用。皮肤老化迹象(诸如皮肤上的皱纹和老年斑)是青春消失的一个不受欢迎的提醒。因此,在现今重视青春的社会中,处理皮肤老化迹象已成为急速发展的行业。
皮肤由多种不同的细胞组成,这些细胞以动态、复杂的关系一起发挥作用以维持皮肤的健康。然而,随着皮肤细胞老化或受损,它们可能会失去维持年轻、健康的皮肤所需的功能。皮肤细胞可能会受到多种内源性和外源性应激源(例如紫外线辐射、污染、吸烟)的损伤。在一些情况下,这些应激源可导致反应性氧物质(ROS)的产生,从而干扰正常的细胞过程。作为反应,细胞已进化出对抗ROS的防御能力,但细胞的防御能力可能会被应激源诱导的ROS的峰值所淹没,从而不仅导致细胞内稳态的急性改变,还导致细胞内稳态的慢性改变。当ROS随时间聚积时,它们在细胞水平上引起氧化应激,这最终可表现为可见的老化迹象(例如,细纹、皱纹、色素沉着过度斑、皮肤变薄)。
肽在护肤组合物中的用途通常是已知的。可商购获得的肽的种类和这些肽的护肤有益效果的范围可使它们成为用于护肤组合物的有吸引力的成分。例如,US 9,597,274描述了使用衍生自生长因子(诸如生长分化因子11)的肽来改善皮肤的健康和/或外观。又如,US 10,668,000描述了可含有多种不同肽的护肤组合物,这些肽在ECM蛋白的合成中是活性的并且通常改善皮肤外观。然而,肽可能是昂贵的,尤其是已知提供护肤有益效果的那些。因此,通常以相对低的量将肽添加到护肤组合物中,因此选择在低浓度下提供良好功效的肽可能是重要的。
因此,期望提供一种含肽护肤组合物,其可以改善人类皮肤,特别是表现出可见老化迹象的皮肤的健康和外观。具体地,期望提供一种含肽护肤组合物,其通过靶向参与这些生物化学通路组的特定基因来改善皮肤细胞中的细胞能量产生和/或ECM修复和更新过程。还期望提供一种在低浓度下提供期望功效的肽的组合。
发明内容
本文公开了一种护肤组合物,该护肤组合物包含:棕榈酰二肽-7(pal-KT)和乙酰基四肽-11(ac-PPYL)[SEQ ID NO:1]的组合;以及皮肤病学可接受的载体;还公开了一种处理皮肤状况的方法,该方法包括将本文的新型组合物施用于期望处理的目标皮肤部分。肽的组合可以改善细胞ATP水平和/或上调参与ECM修复和更新过程的某些基因,在一些情况下两者协同地进行。
具体实施方式
肽用于改善皮肤的健康和外观的用途通常是已知的。然而,现已令人惊讶地发现棕榈酰二肽-7(“pal-KT”)和乙酰基四肽-11(ac-PPYL)[SEQ ID NO:1]的组合可促进细胞能量产生和ECM修复和更新过程。具体地,选择pal-KT和ac-PPYL[SEQ ID NO:1]的组合可协同地调节已知参与细胞生物能学和ECM修复和更新的关键基因的表达。改善细胞能量产生和/或ECM修复和更新对于改善皮肤,特别是表现出可见老化迹象的皮肤的健康和/或外观是重要。
本文对“实施方案”或类似方法的引用意指与该实施方案结合描述的具体材料、特征、结构和/或特性被包括在至少一个实施方案、任选多个实施方案中,但这并不意味所有实施方案包括所描述的材料、特征、结构和/或特性。此外,材料、特征、结构、和/或特性可以任何合适的方式结合在不同的实施方案中,并且材料、特征、结构、和/或特性可以省略或替换所描述的。因此,除非另外说明或声明不相容性,否则尽管未在组合中明确地例示,本文所述的实施方案和方面可包括其它实施方案和/或方面的元件或组件或者可与其它实施方案和/或方面的元件或组件组合。
在所有实施方案中,除非另外特别说明,否则所有成分百分比均基于化妆品组合物的重量计。除非另外特别说明,否则所有比率均为重量比。有效数字的数表示既不表达对所示量的限制,也不表达对测量精确性的限制。所有数值应理解为被词“约”修饰,除非另外特别指明。除非另外指明,否则所有测量均被理解为是在大约25℃和环境条件下进行的,其中“环境条件”意指在约1个大气压和约50%相对湿度下的条件。所有数值范围都是包含性的并且能够组合以形成未明确公开的较窄范围。例如,所描绘的范围上限和下限是可互换的,以形成另外的范围。
本发明的组合物可包含本文所述的基本组分以及任选的成分,基本上由其组成或由其组成。如本文所用,“基本上由...组成”意指组合物或组分可仅包含如下附加成分,所述附加成分不在本质上改变受权利要求书保护的组合物或方法的基本特征和新颖特征。如说明书和所附权利要求书中所用,除非上下文另外清楚地指明,否则单数形式“一个”、“一种”和“该(所述)”旨在也包括复数形式。
序列表
列出SEQ ID NO:1的氨基酸或核苷酸序列以及SEQ ID NO:2和SEQ ID NO:3的核苷酸序列(它们是一级序列并且包括其保守修饰的变体)的序列表作为名称为“15965_seq_list_ST25”的ASCII文本文件与本申请同时提交。该ASCII文本文件创建于2021年1月19日并且大小为138KB。根据MPEP§605.08和37 CFR§1.52(e),该ASCII文本文件中的主题以引用方式并入本文。
定义
“约”通过指代等于加上或减去指定值的百分之二十(+/-20%)以下(例如,小于15%、10%或甚至小于5%)的范围来修饰特定值。
如参照组合物所用的“施用(Apply或application)”意指将本发明的组合物施用或铺展到人类皮肤表面,诸如表皮上。
“化妆品组合物”意指包含美容剂并且旨在用于非治疗性(即非医学)用途的组合物。化妆品组合物的示例包括有色化妆品(例如粉底、唇膏、遮瑕物和睫毛膏)、护肤组合物(例如保湿剂和防晒剂)、个人护理组合物(例如洗去型和免洗型沐浴剂和皂)、毛发护理组合物(例如洗发剂和调理剂)。
本文中“衍生物”意指给定化合物的酰胺、醚、酯、氨基、羧基、乙酰基和/或醇衍生物。
“有效量”是指足以在处理期的过程内显著诱导对角质组织的积极有益效果的化合物或组合物的量。积极有益效果可为健康、外观和/或感觉有益效果,其包括独立的或组合的本文所公开的有益效果。在一个具体示例中,蔗糖酯和脂肪醇的有效量是足以增加由于氧化应激而降低的细胞ATP水平的量。
“护肤”是指调节和/或改善皮肤状况(例如,皮肤健康、外观或质地/感觉)。改善皮肤状况的一些非限制性示例包括通过提供更光滑、更均匀的外观和/或感觉来改善皮肤外观和/或感觉;增加皮肤的一个或多个层的厚度;改善皮肤的弹性或回弹性;改善皮肤的紧致度;和减少皮肤的油性的、有光泽的、和/或无光泽的外观、改善皮肤的水合状态或保湿状态、改善细纹和/或皱纹的外观、改善皮肤剥落或脱屑、使皮肤丰满、改善皮肤屏障特性、改善肤色、减少发红或皮肤疹斑的外观、和/或改善皮肤的亮度、光彩、或半透明性。
“护肤活性物质”是指当施用于皮肤时,向皮肤或通常存在于其中的细胞类型提供即时和/或长久有益效果的化合物或化合物的组合。护肤活性物质可调节和/或改善皮肤或其相关细胞(例如,改善皮肤弹性、水合、皮肤屏障功能,和/或改善细胞代谢)。
“护肤组合物”意指包含护肤活性物质并且调节和/或改善皮肤状况的组合物。
“协同作用”及其变型形式意指由棕榈酰二肽-7(pal-KT)和乙酰基四肽-11[SEQID NO:1]的组合提供的细胞能量产生和/或ECM修复效果大于这些成分单独的预期加性效应。例如,当pal-KT和乙酰基四肽-11的组合[SEQ ID NO:2]使PPARA[SEQ ID NO:2]和/或MSMO1[SEQ ID NO:3]的上调增加超过这些成分各自的计算加性效应时,证明存在协同作用。
如本文所用,“处理期”是指将材料或组合物施用至目标皮肤表面的时间长度和/或频率。
“上调”及其变型形式意指基因表达的增加。相反,“下调”意指基因表达的减少。相对于特定基因,上调和下调可根据下文更详细描述的基因调节测定来确定。
皮肤护理组合物
本文的新型护肤组合物旨在局部施用于人类皮肤以改善细胞能量产生和/或ECM的健康。本发明的护肤组合物含有安全有效量的棕榈酰二肽-7(pal-KT)和乙酰基四肽-11(ac-PPYL)[SEQ ID NO:1]。有效量的这两种成分的组合已经被证实上调了PPARA[SEQ IDNO:2]和MSMO1[SEQ ID NO:3],因此该组合被认为参与细胞能量产生。参见,Lopez-Leon,S等人,“Sports genetics:the PPARA gene and athletes'high ability in endurancesports.Asystematic review and meta-analysis”,Biology of sport,第33,1卷(2016年):第3-6页。有效量的pal-KT和ac-PPYL[SEQ ID NO:1]还可以协同地上调MSMO1(SEQ IDNO:3),二者被认为参与胆固醇合成并参与皮肤屏障的修复和更新。参见He M.等人,“Therole of sterol-C4-methyl oxidase in epidermal biology”,Biochim BiophysActa.2014年3月;1841(3):331-5。
已经证实PPARA和MSMO1由于皮肤的真皮老化(即,真皮的时间性老化和/或光老化)而下调。然而,在一些情况下,pal-KT和ac-PPYL[SEQ ID NO:1]的组合协同地上调这些基因,并且甚至可以表现出1.2或更大(例如,1.3、1.4、1.5、1.6、1.7、1.8或1.9或更大)的因子的协同作用。本文的组合物可包含10:1至1:10(例如,5:1至1:10、5:1至1:5、1:1至1:5或1:1至1:10)的pal-KT与ac-PPYL[SEQ ID NO:1]的重量比。
本文的护肤组合物可为化妆品组合物、药物组合物或药用化妆品组合物,并且可以各种产品形式提供,包括但不限于溶液、悬浮液、乳液、霜膏、凝胶、调色剂、条棒、喷剂、气溶胶剂、软膏剂、清洁液体洗涤剂和固体棒、糊剂、泡沫、摩丝、剃刮膏、擦拭物、条、贴片、电动贴片、水凝胶、成膜产品、面部和皮肤面膜(带有和不带有不溶性片材)、化妆品诸如粉底、眼线和眼影等。在一些情况下,所述组合物形式可符合所选的具体皮肤病学可接受的载体。例如,组合物(和载体)可以乳液(例如,油包水、水包油或水包油包水)或含水分散体的形式提供。
本文的组合物可通过制备局部用护肤组合物的常规方法来制备。此类方法通常包括在一个或多个步骤中将各成分混合至相对均一的状态,可使用或不使用加热、冷却、施加真空等。优选地制备组合物以优化稳定性(物理稳定性、化学稳定性、光稳定性)和/或活性物质的递送。这种优化可以包括适当的pH(例如,小于7)、排除可以与活性剂络合并因此对稳定性或递送造成负面影响的物质(例如,排除污染性铁)、使用防止络合物形成的方法(例如,适当的分散剂或双隔室包装)、使用适当的光稳定性方法(例如,结合防晒剂、防晒霜,使用不透明包装)等。
维生素B3化合物
本文的组合物可任选地包含安全有效量的维生素B3化合物。在一些情况下,本发明的组合物可以含有基于组合物的重量或体积的按重量计0.01%至10%(例如0.1%至10%、0.5%至5%或甚至1%至%)的维生素B3化合物。
如本文所用,“维生素B3化合物”是指具有下式的化合物:
其中:R为CONH2(即烟酰胺)、COOH(即烟酸)或CH2OH(即烟醇);它们的衍生物;以及前述物质中的任一种的盐。
维生素B3化合物的示例性衍生物包括烟酸酯,该烟酸酯包括非血管舒张性烟酸酯(例如烟酸生育酚酯、烟酸十四烷酯)、烟酰胺核苷、烟基氨基酸、羧酸的烟醇酯、烟酸N-氧化物和烟酰胺N-氧化物。
二肽
本文的组合物包含安全有效量的棕榈酰化二肽,pal-KT(INCI:棕榈酰二肽-7)。在一些情况下,pal-KT可以0.0001%至3%(例如,0.001%至2%、0.01%至1%或0.1%至0.5%)存在于本发明的组合物中。Pal-KT以商品名得自Sederma(France)。
四肽
本文的组合物包含安全有效量的乙酰化四肽ac-PPYL[SEQ ID NO:2](INCI:乙酰基四肽-11)。在一些情况下,ac-PPYL可以0.0001%至3%(例如,0.001%至2%、0.01%至1%或0.1%至0.5%)存在于本发明的组合物中。Ac-PPYL以商品名SYNIORAGE得自BASFCare Creations(New Jersey)。
皮肤病学可接受的载体
本文的组合物包括皮肤病学可接受的载体(其可称为“载体”)。短语“皮肤病学可接受的载体”是指该载体适于局部施用于角质组织,具有良好的美学性质,与组合物中的活性物质相容,并且不引起任何不合理的安全或毒性问题。在一个实施方案中,载体以按组合物的重量计约50%至约99%、约60%至约98%、约70%至约98%、或约80%至约95%的含量存在。
载体可为多种形式。在一些情况下,组分(例如提取物、防晒活性物质、附加组分)的溶解度或分散度可决定载体的形式和特征。非限制性示例包括简单溶液(例如含水的或无水的)、分散体、乳液和固体形式(例如凝胶、条棒、可流动的固体或无定形材料)。在一些情况下,皮肤病学可接受的载体为乳液的形式,该乳液具有连续水相(例如水包油或水包油包水乳液)或连续油相(例如油包水或油包水包油乳液)。乳液的油相可包含硅油、非硅油(诸如烃油、酯、醚)以及它们的混合物。水相可包含水和水溶性成分(例如,水溶性保湿剂、调理剂、抗微生物剂、湿润剂和/或其它护肤活性物质)。在一些情况下,水相可包含不是水的组分,该组分包括但不限于水溶性保湿剂、调理剂、抗微生物剂、湿润剂和/或其它水溶性护肤活性物质。在一些情况中,组合物的非水组分包括湿润剂,诸如甘油和/或其它多元醇。
在一些情况下,本文的组合物为提供轻度且非油腻的知觉感觉的水包油(“O/W”)乳液的形式。本文的合适O/W乳液可包含按组合物的重量计大于50%的连续水相,并且剩余部分为分散的油相。水相可包含基于水相的重量计1%至99%的水,以及任何水溶性和/或与水混溶的成分。在这些情况下,分散的油相将通常以按组合物的重量计小于30%(例如,1%至20%、2%至15%、3%至12%、4%至10%、或甚至5%至8%)存在,以帮助避免油性组合物的一些不期望的感觉效果。油相可包括一种或多种挥发性油和/或非挥发性油(例如,植物油、有机硅油和/或烃油)。可适用于本发明组合物的油的一些非限制性示例公开于美国专利9,446,265和美国公布2015/0196464中。
载体可包含一种或多种皮肤病学可接受的稀释剂。如本文所用,“稀释剂”是指本文的护肤活性物质能够分散、溶解或以其它方式掺入其中的材料。亲水性稀释剂的一些非限制性示例包括水、有机亲水性稀释剂诸如低级一价醇(例如C1-C4)和低分子量二醇和多元醇,包括丙二醇、聚乙二醇(例如分子量200g/mol至600g/mol)、聚丙二醇(例如分子量425g/mol至2025g/mol)、甘油、丁二醇、1,2,4-丁三醇、山梨醇酯、1,2,6-己三醇、乙醇、异丙醇、山梨醇酯、丁二醇、醚丙醇、乙氧基化醚、丙氧基化醚以及它们的组合。
调理剂
本文的组合物可包含按重量计0.1%至50%的调理剂(例如,0.5%至30%、1%至20%、或甚至2%至15%)。添加调理剂可有助于为组合物提供期望的感觉特性(例如,施用时丝滑、润滑的感觉)。调理剂的一些非限制性示例包括烃油和蜡、硅氧烷、脂肪酸衍生物、胆固醇、胆固醇衍生物、甘油二酯、甘油三酯、植物油、植物油衍生物、乙酰甘油酯、烷基酯、烯基酯、羊毛脂、蜡酯、蜂蜡衍生物、甾醇和磷脂、它们的盐、异构体和衍生物、以及它们的组合。特别合适的调理剂示例包括挥发性或非挥发性硅氧烷流体,诸如聚二甲基硅氧烷共聚多元醇、二甲基聚硅氧烷、二乙基聚硅氧烷、混合的C1-30烷基聚硅氧烷、苯基聚二甲基硅氧烷、聚二甲基硅氧烷醇、聚二甲基硅氧烷、聚二甲基硅氧烷醇、硅氧烷交联聚合物、以及它们的组合。聚二甲基硅氧烷可为尤其合适的,因为一些消费者将由某些聚二甲基硅氧烷流体提供的感觉特性与良好的保湿相关联。可适用作调理剂的硅氧烷流体的其它示例描述于美国专利5,011,681中。
流变改性剂
本文的组合物可包含0.1%至5%的流变改性剂(例如增稠剂)以向组合物提供合适的流变学和皮肤感觉特性。增稠剂的一些非限制性示例包括交联的聚丙烯酸酯聚合物、聚丙烯酰胺聚合物、多糖、树胶、以及它们的混合物。在一个特别合适的示例中,组合物可包含超吸收聚合物增稠剂,诸如聚丙烯酸钠、淀粉接枝的聚丙烯酸钠、或这些物质的组合。超吸收聚合物增稠剂的一些非限制性示例描述于例如美国专利9,795,552中。
一些消费者发现使用硅氧烷流体作为调理剂的组合物具有不期望的油腻感或厚重感。因此,可能期望提供不含或基本上不含硅氧烷流体的组合物。还可能期望定制超吸收聚合物增稠剂以例如通过调节组合物中水的量、水:油比率(例如,12:1至1:1)、和/或水与增稠剂或油与增稠剂的比率来为组合物提供轻盈的透气感。
乳化剂
当皮肤病学可接受的载体为乳液形式时,可能希望包含乳化剂以提供稳定组合物(例如,不发生相分离)。当包含乳化剂时,乳化剂可以0.1%至10%(例如,1%至5%、或2%至4%)的量存在。乳化剂可为非离子型、阴离子型或阳离子型。可适用于本文的乳化剂的一些非限制性示例公开于美国专利号3,755,560;4,421,769和McCutcheon的“洗涤剂和乳化剂(Detergents and Emulsifiers)”,北美版第317-324页(1986年)中。
其它任选成分
本发明的组合物可任选地包含一种或多种常用于化妆品组合物中的附加成分(例如,着色剂、皮肤护理活性物质、抗炎剂、防晒剂、乳化剂、缓冲液、流变改性剂、这些的组合等),前提条件是该附加成分不会不利地改变由本发明组合物提供的皮肤健康或外观有益效果。当掺入组合物中时,附加成分应该适用于与人类皮肤组织接触,而没有不适当的毒性、不相容性、不稳定性、变应性应答等等。附加活性物质的一些非限制性示例包括维生素、矿物质、肽和肽衍生物、糖胺、防晒剂、控油剂、颗粒、类黄酮化合物、毛发生长调节剂、抗氧化剂和/或抗氧化剂前体、防腐剂、蛋白酶抑制剂、酪氨酸酶抑制剂、抗炎剂、保湿剂、剥落剂、亮肤剂、免晒美黑剂、润滑剂、抗痤疮活性物质、抗蜂窝炎活性物质、螯合剂、抗皱纹活性物质、抗萎缩活性物质、植物甾醇和/或植物激素、N-酰基氨基酸化合物、抗微生物剂和抗真菌剂。可以适用于本文的附加成分和/或护肤活性物质的其它非限制性示例描述于美国专利公布号2002/0022040、2003/0049212、2004/0175347、2006/0275237、2007/0196344、2008/0181956、2008/0206373、2010/00092408、2008/0206373、2010/0239510、2010/0189669、2010/0272667、2011/0262025、2011/0097286、US2012/0197016、2012/0128683、2012/0148515、2012/0156146和2013/0022557,以及美国专利号5,939,082、5,872,112、6,492,326、6,696,049、6,524,598、5,972,359和6,174,533中。
当在本文的组合物中包含任选成分时,可能期望选择不与组合物中的其它成分,尤其是对pH敏感的成分如烟酰胺、水杨酸盐和肽形成络合物或以其它方式不期望地相互作用的成分。当存在时,任选成分可以按组合物的重量计0.0001%至50%;0.001%至20%;或甚至0.01%至10%(例如,50%、40%、30%、20%、10%、5%、4%、3%、2%、1%、0.5%或0.1%)的量被包含。
使用方法
本发明的方法包括识别期望处理的目标皮肤部分,以及将包含有效量的维生素B3化合物、pal-KT、ac-PPYL[SEQ ID NO:1]以及任选地一种或多种附加护肤活性物质的组合物施用于目标皮肤部分。目标皮肤部分可在面部皮肤表面上(诸如前额、口周、颏、眶周、鼻部和/或面颊)或身体的另一部分(例如手、臂、腿、背、胸)。需要处理的人或目标皮肤部分可以是表现出皮肤老化迹象(例如,细纹、皱纹、色素沉着过度斑)的人或目标皮肤部分。在一些情况下,目标皮肤部分可能不表现出皮肤老化迹象,但是如果该皮肤部分是已知表现出可见老化迹象的皮肤部分(例如,暴露于阳光的皮肤),则使用者可能仍然希望处理该皮肤部分。以这种方式,本发明的方法和组合物可以预防性地用于帮助延迟可见的皮肤老化迹象。
可在处理期期间向目标皮肤部分,并且如果需要,向周围皮肤以每天至少一次、每天两次或以每天更频繁次数的方式施用组合物。当每天两次地施用时,第一次与第二次施用相隔至少1至12个小时。通常,组合物可在早上和/或晚上临睡觉前施用。本文的处理期理想地为对于pal-KT和ac-PPYL[SEQ ID NO:1]而言足以改善皮肤外观的时间。处理期可持续至少1周(例如,约2周、4周、8周或甚至12周)。在一些情况下,处理期将延长多个月(即3个月至12个月)。在一些情况下,组合物可在一周中的大多数时间(例如,每周至少4天、5天或6天)施用,在至少2周、4周、8周或12周的处理期期间至少每天一次或甚至每天两次。
施用组合物的步骤可通过局部施用来实现。关于组合物的施用,术语“局部的”、“局部”、“局部地”是指将组合物递送到目标区域(例如,皱纹或其部分)而使对不期望处理的皮肤表面的递送最小化。组合物可施用到并且轻轻揉进皮肤区域中。组合物或皮肤病学可接受的载体的形式应被选择成有利于局部施用。虽然本文的某些实施方案设想将组合物局部施用到某一区域,但应当理解,本文的组合物可更全面地或广泛地施用到一个或多个皮肤表面。在某些实施方案中,本文的组合物可以用作多步美容方案的一部分,其中本发明的组合物可以在一种或多种其它组合物之前和/或之后施用。
基因调节测定
该方法提供了测量化合物或材料调节靶基因诸如PPARA[SEQ ID NO:2]或MSMO1[SEQ ID NO:3]表达的能力的方式。
细胞:叔角质细胞(tKC)
BJ成纤维细胞
铺板:在处理前一天对细胞进行铺板。
对于叔角质细胞:针对12孔板(例如,I型胶原包被的板,Corning目录号356500),在2ml体积培养基/孔中100,000个细胞/孔;或对于24孔板,在1ml体积培养基/孔中50,000个细胞/孔。
对于BJ成纤维细胞:针对12孔板(例如,Corning目录号3512),在2ml体积培养基/孔中88,000个细胞/孔;或对于24孔板,在1ml体积培养基/孔中44,000个细胞/孔。
培养基:对于叔角质细胞:EpiLife(例如,Thermo Fisher Scientific目录号MEPI500CA+HKGS(例如,Thermo Fisher Scientific目录号S-001-5)。
对于BJ成纤维细胞:EMEM(例如,ATCC目录号30-2003)+10% FBS(例如,HyClone目录号SH30071.02)。
在培养基中进行处理并等分到剂量板中。当需要处理细胞时,将所有的细胞板同时从培养箱中取出。一次使用一个板,除去培养基并加入处理物,如下:
--从细胞板中滗出培养基。
--将倒置的板简单地在纸巾上吸干。
--将盖子放回到板上,并将板移入生物安全柜中。
--使用多通道移液管将处理物从剂量板转移至细胞板,一次一个柱。
一旦所有板都被处理,将它们移入37℃、5% CO2和90%湿度的培养箱中。在处理期结束前约15分钟至30分钟,经由显微镜观察来自每个处理的代表性孔的细胞,然后将板放回培养箱中。当处理时间结束时,将所有板从培养箱中取出。从每个板中滗出培养基,并将板在纸巾上吸干。将350μl Qiagen Buffer RLT添加到每个孔中以使细胞裂解,并将裂解物转移到2ml Eppendorf管中并于-20℃储存直至准备用于基因组学。
Wafergen方法:总RNA纯化和qPCR
将细胞裂解物在4℃解冻,然后使用Biomek FxP和RNAdvance组织分离试剂盒(Beckman Coulter,部件编号A32646)分离。使用Nandrop 8000(Nanodrop,ND-8000)定量所得的RNA。使用500ng总RNA和Applied Biosystems High Capacity cDNA与逆转录测试试剂盒(Applied Biosystems部件编号4368814)产生cDNA。使用Wafergen Nanodispenser将PrimeTime GeneExpression MasterMix(IDT,部件编号1055771)的cDNA、测定物和稀释液铺板到Wafergen MyDesign SmartChip(TakaraBio,部件编号640036)上。然后将玻片加载到SmartChip循环仪中并使用以下PCR条件进行qPCR:
保持阶段:50℃达2分钟(加热),然后95℃达10分钟。
PCR阶段(40个循环):95℃达15秒,然后60℃达1分钟。
以.txt文件格式导出数据用于分析。
过氧化氢应激的ATP测定
皮肤细胞(例如角质细胞和成纤维细胞)通过使用能量产生酶和还原当量(例如GSH)来对抗反应性氧物质,这导致细胞ATP水平的耗竭。较低的能量水平使得细胞易于降低适应和正常发挥功能的能力。因此,增加细胞ATP水平可帮助细胞对抗应激并维持用于正常稳态的足够能量。
过氧化氢是众所周知的ROS替代物。当用高水平(例如200μM至500μM)的过氧化氢处理皮肤细胞时,一小时内在未受应激的细胞中观察到细胞ATP水平降低约10%。细胞ATP水平可以用来自Promega的CELL TITER GLO牌测定试剂盒或等同物定量,其中发光信号与存在的ATP的量成比例。
方法概述:
使用来自储备的膨胀tKC进行该测定。将细胞在培养瓶中扩增5天,胰蛋白酶化,接种,然后在96孔板中生长。在96孔板中生长1天后,不处理也不应激第1柱细胞,用过氧化氢(培养基中300μM)处理第2柱至第12柱细胞,不用测试材料处理第2柱,而用测试材料的系列稀释液处理第3柱至第12柱达1小时(37℃,5% CO2培养箱)。
细胞制备:
1.将细胞以10,000个细胞/孔、100uL总体积/孔接种在合适的96孔板(例如,CORNING牌白色透明底板#3903或等同物)中。
2.将细胞在37℃、5% CO2、95%湿度下培养24小时直至处理日。例如,可在星期一接种细胞并在星期二测定。
处理:
1.从细胞板中吸出培养基。
2.向第1柱孔A1至H1中添加100uL培养基。
3.向第2柱至第12柱的所有孔中添加含有300μM过氧化氢的100μL培养基。
4.向第2柱(A2至H2)中添加载体对照,并向第3柱至第11柱中添加1uL处理的系列稀释液。
5.向第12柱的所有孔中添加1μl 40.9mM烟酰胺,使烟酰胺的最终水平为409μM(阳性对照)。
6.在37℃、5% CO2培养箱中放置1小时。
7.从所有孔中吸出培养基。
8.根据制造商说明书向每个孔中添加100uL CELL TITER GLO牌试剂。
9.在室温下温育5分钟至10分钟。
10.在合适的读板机上读取发光值。
发光检测:
使用来自BioTek的SYNERGY NEO牌读板机或等同物。
实施例
实施例1:制剂。
下表1提供了本发明的护肤组合物的实施例。通过用合适的搅拌器(例如,TekmarRW20DZM或等同物)共混A相组分并加热至70℃至80℃的温度,并且在搅拌的同时保持温度,来制备示例性组合物。单独地,用合适的搅拌器共混B相组分并加热至70℃至75℃,同时在混合期间保持温度。将相B添加到相A中,同时充分混合以形成水包油(O/W)乳液。然后使用合适的研磨机(例如,Tekmar T-25或等同物)将乳液研磨5分钟。当乳液处于60℃时,添加相C,同时继续混合。处于40℃时,将相D和相E的成分添加到乳液。然后将乳液研磨5分钟以提供均匀的组合物。
表1
实施例2:pal-KT和Ac-PPYL[SEQ ID NO:1]协同地上调PPARA[SEQ ID NO:2]和 MSMO1[SEQ ID NO:3]。
该实施例证明了pal-KT和ac-PPYL[SEQ ID NO:1]的组合能够协同地上调PPARA[SEQ ID NO:2]。如上文在基因调节测定中所述制备了测试组合物和对照组合物,并相应地进行了测试。该实施例中使用的pal-KT是来自Sederma(France)的PALESTRINA牌pal-KT,ac-PPYL是来自BASF Care Creations(New Jersey).的SYNIORAGE牌四肽。该测试的结果汇总于下表2中。P+A是指pal-KT(P)和ac-PPYL(A)[SEQ ID NO:1]的组合。
协同因子计算如下:
其中p值≤0.05的大于1.00的协同因子指示统计意义上显著的协同效应。优选的协同因子为1.3或更大。
表2
如表2中可见,并不是pal-KT和ac-PPYL[SEQ ID No:1]的所有组合都产生期望的协同效应。含有1ppm pal-KT(pal-KT与四肽的比率为1:13.5至100:1.35)的测试样品组合对于上调MSMO1[SEQ ID NO:3]没有表现出1.3或更大的协同因子。含有7.5ppm pal-KT的测试样品组合在约1:2的比率下仅表现出所期望的上调PPARA[SEQ ID NO:2]的协同作用,尽管其它组合表现出较低的协同地上调PPARA[SEQ ID NO:2]的能力。含有1ppm的测试样品中的仅一个测试样品能够协同地上调PPARA[SEQ ID NO:2],并且没有一个测试样品表现出1.3或更大的协同因子。因此,数据表明,肽的浓度和肽的比率对于上调PPARA[SEQ ID NO:2]和MSMO1[SEQ ID NO:3]都可能是重要的。
实施例3:pal-KT和ac-PPYL[SEQ ID NO:3]改善细胞生物能学。
该实施例证明了pal-KT和ac-PPYL[SEQ ID NO:3]能够对抗ROS诱导的ATP耗竭。暴露于过氧化氢(一种众所周知的反应性氧物质)的测试细胞通常将表现出降低的ATP水平。可以恢复由于暴露于ROS而耗竭的ATP水平的测试试剂是期望的。可协同地恢复ATP水平并表现出1.3或更大的协同因子的测试试剂是优选的。根据上述过氧化氢应激的ATP测定来测试肽。该测试的结果汇总于下表3中。其中p值≤0.05的大于1.00的协同因子指示统计意义上显著的协同效应。优选的协同因子为1.3或更大。
表3:ROS诱导的ATP恢复
如表3所示,并不是pal-KT和ac-PPYL[SEQ ID NO:1]的所有组合都能协同地恢复细胞内ROS耗竭的ATP水平。事实上,仅含有比率为约10:1至1:10的pal-KT和ac-PPYL的组合能够协同地增加ATP产生。在该实施例中,pal-KT与ac-PPYL[SEQ ID NO:1]的比率为约1:1的测试样品似乎表现出最高的协同因子。
实施例4:二肽特异性。
该实施例证明了选择特定二肽以提供PPARA[SEQ ID NO:2]和/或MSMO1[SEQ IDNO:3]的期望的协同上调的重要性。在该测试中,来自pal-KT的氨基酸重排以形成新的二肽pal-TK。如上文在基因调节测定中所述制备了测试组合物和对照组合物,并相应地进行了测试。该测试的结果汇总于下表4中。倍数变化因子计算如下。
需要大于1的倍数变化因子,优选1.3或更大的倍数变化因子。
令人惊奇的是,pal-KT能够比pal-TK显著更好地上调PPARA[SEQ ID NO:2]和MSMO1[SEQ ID NO:3],并且对于上调PPARA[SEQ ID NO:2]和MSMO1[SEQ ID NO:3]表现出大于1.3的倍数变化因子。
表4-pal-KT对pal-TK的特异性
令人惊讶地,如表4中可见,具有与pal-KT相同的氨基酸但以不同顺序排列的二肽不提供期望的协同效应。这些数据表明特定的肽序列对于提供期望的协同作用是重要的。
示例性组合
A.一种护肤组合物,包含:
a)棕榈酰二肽-7(pal-KT)和乙酰基四肽-11(ac-PPYL)[SEQID NO:1]的组合,其中该pal-KT和ac-PPYL[SEQ ID NO:1]的组合上调PPARA(SEQ ID NO:2)和MSMO1(SEQ ID NO:3)中的至少一者;以及
b)皮肤病学可接受的载体。
B.根据段落A所述的组合物,其中该pal-KT和ac-PPYL的组合[SEQ ID NO:1]协同地上调PPARA(SEQ ID NO:2)和MSMO1(SEQ ID NO:3)中的至少一者。
C.根据段落A或B所述的组合物,其中该pal-KT和ac-PPYL的组合[SEQ ID NO:1]表现出至少1.3的协同因子。
D.根据任一前述段落所述的组合物,其中该pal-KT以0.00005%至5%存在。
E.根据任一前述段落所述的组合物,其中该ac-PPYL[SEQ ID NO:1]以0.00005%至5%存在。
F.根据任一前述段落所述的组合物,其中该pal-KT和ac-PPYL[SEQ ID NO:1]以10:1至1:10的比率存在。
G.根据任一前述段落所述的组合物,还包含至少一种附加成分,该至少一种附加成分选自维生素、矿物质、肽、糖胺、防晒剂、控油剂、类黄酮化合物、抗氧化剂、蛋白酶抑制剂、酪氨酸酶抑制剂、抗炎剂、保湿剂、剥落剂、亮肤剂、抗痤疮剂、抗皱剂、植物甾醇、N-酰基氨基酸化合物、抗微生物剂、抗真菌剂、pH调节剂、增稠剂、防腐剂以及它们的组合。
H.根据段落G所述的组合物,其中该附加成分包括维生素B3化合物、维生素A化合物、维生素E化合物、糖类或植物提取物。
I.一种用化妆品处理皮肤的方法,包括:
a)识别期望处理的目标皮肤部分;以及
b)在处理期的过程内将根据任一前述段落所述的护肤组合物施用于目标皮肤部分,该护肤组合物包含棕榈酰二肽-7(pal-KT)和乙酰基四肽-11(ac-PPYL)[SEQ ID NO:1]的组合以及皮肤病学可接受的载体。
J.根据段落I所述的方法,其中该pal-KT和ac-PPYL的组合[SEQ ID NO:1]上调PPARA[SEQ ID NO:2]和MSMO1[SEQ ID NO:3]中的至少一者,优选该pal-KT和ac-PPYL的组合[SEQ ID NO:1]协同地上调PPARA[SEQ ID NO:2]和MSMO1[SEQ ID NO:3]中的至少一者。
K.根据段落I所述的方法,其中根据过氧化氢应激的ATP测定,该pal-KT和ac-PPYL的组合[SEQ ID NO:1]改善细胞ATP水平,优选协同地改善细胞ATP水平。
L.根据段落I所述的方法,其中该处理器为至少2周。
M.根据段落所述的方法,其中该方法改善可见的皮肤老化迹象。
N.一种协同地上调皮肤细胞内PPARA[SEQ ID NO:2]和MSMO1[SEQ ID NO:3]中的至少一者的方法,包括:使皮肤与有效量的pal-KT和ac-PPYL[SEQ ID NO:1]的组合接触,其中该有效量的pal-KT和ac-PPYL[SEQ ID NO:1]上调PPARA[SEQ ID NO:2]和MSMO1[SEQ IDNO:3]中的至少一者。
本文所公开的量纲和值不应理解为严格限于所引用的精确数值。相反,除非另外指明,否则每个此类量纲旨在表示所述值以及围绕该值功能上等同的范围。例如,公开为“40mm”的量纲旨在表示“约40mm”。
除非明确排除或以其它方式限制,本文中引用的每一篇文献,包括任何交叉引用或相关专利或专利申请以及本申请对其要求优先权或其有益效果的任何专利申请或专利,均据此全文以引用方式并入本文。对任何文献的引用不是对其作为与本发明的任何所公开或本文受权利要求书保护的现有技术的认可,或不是对其自身或与任何一个或多个参考文献的组合提出、建议或公开任何此类发明的认可。此外,当本发明中术语的任何含义或定义与以引用方式并入的文献中相同术语的任何含义或定义矛盾时,应当服从在本发明中赋予该术语的含义或定义。
虽然已示出和描述了本发明的具体实施方案,但是对于本领域技术人员来说显而易见的是,在不脱离本发明的实质和范围的情况下可作出各种其它变化和修改。因此,本文旨在于所附权利要求中涵盖属于本发明范围内的所有此类变化和修改。
序列表
<110> 宝洁公司
<120> 护肤组合物及其使用方法
<130> 15965
<160> 3
<170> PatentIn版本3.5
<210> 1
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述:乙酰基四肽-11(ac-PPYL)
<400> 1
Pro Pro Tyr Leu
1
<210> 2
<211> 93231
<212> DNA
<213> 智人(Homo sapiens)
<400> 2
gtggacgcgg cggccccgcg gcgggggcag cgggcggcgg gggcggaggc ggccgctagc 60
gccctgcccg gcgccgcctc cttcggcgtt cgccccacgg accggcaggc ggcggaccgc 120
ggcccaggtg cccgggggcg ggcgggcggg cgggcgggaa cgcgcgcggg ggtccgcggt 180
ccgggcttcc caggtcccgg gacccggagg gcggcggacg ggggaggggc aggggctggg 240
cggcgcatgc gcggggcccg gggtctcggg gtctccgggt cccggggacc cgggggcccg 300
gggtgcgcgg ctggggacct gagggcgagg agcgaggaca cacaccgagg actcttgcga 360
gggatctcgg ggcccagctc ggcctccctc ctagcgctgg gggcctgccc ggaacccgag 420
tccgcggctg tccctggggt ttggcgctgc gcggaggtcg ggtctgggga ccgcagcgac 480
tctgggtctt cgggttgtcc cctcggaggg agggcccacg ggcggggaca tcgggacttg 540
ccctttcctc ggcgcagcgg agctggggcg tcgccgactc agaaggtgct ttccgagacc 600
tccagggatc tccgaggcga ggaaacccgg gccccggaca gaccgaccct gggtgggtgc 660
gcccggcttc tgccgtcgga cggagacgcg cgtgtttgtt cctccagctg cgaccacctt 720
tgaggaacgg ttcccacttt gtgccccaac gcggcggggc gaccccggac aggctgcgct 780
gggccgggtg gcttctctgc ggaagccgcg ccacgtcgct cccggtcggg gccgctgagg 840
gtcgggcgcc caggtctttc cggagtcccg ggctgcgcgg cccgcgtggt gcgggtgaag 900
ctggaggggc gcggggtggt gccagtggaa gtcaggaggg tcggccctgc cccctcacgc 960
accccaaccg ggcacaactg cacgcctgtg cttttctgaa gtctttttta aaagttaaaa 1020
gagaggaagt gtgctccaag tgtcaggatt ctttccaaga aaaacccaca gttgtccaat 1080
ggcctgggct tcgtgggacc tccggggctg cacgcccacg tcagcctcag ccgacccctg 1140
ccaggaaacc agggaggccc ctcctctccc agcctccttg ggataagggt gccttgggga 1200
actgggtcag ggcaaggaca cgggattttc ctgggaagga ccctgcgaca cccgtgtcgt 1260
tgcggggcag ggtcagcatg actttcctct tccaaggtga agagttgggg ggcatccaga 1320
gaacaaccgt aatcacttcc tccttcacct tcttactgcc aggctgaagc tcagggccct 1380
gtctgctctg tggactcaac agtttgtggc aagacaagct cagaactgag aagctgtcac 1440
cacaggtaaa tagaaggttt aatttactgt ttccagatgg aaatatttaa gtgttttcag 1500
tgtttacttc tgttgcacta cagaccagca atctgggggt tattactttg tgatgcaagg 1560
ttagatacgt tttcagactg aaagtaaaat acatgtgcat ggattcattt tttttttttt 1620
tttttttttt tgagacggag tctcgctctg ccgcccaggc tggagtgcag tggcctaatc 1680
tcagatcaca gcaacctctg ccactggggt tcaagcgatt ctcttgcctc agcctcccga 1740
gtagctggga ttacaggcgc ctgccaccat gcccagctaa tttttgtagt tttagtagag 1800
gcggggtttc accatcttgg ccaggctgat cttgaactcc tgacctcatg atccacctgt 1860
tcctcccaaa gtgctgggat tacagacgtg agccaccgtg cctggcctag gattcacttt 1920
gaagttctga gttattgtgt gacttttgct aggaacttca ttgcttcgtg gcaggcatgt 1980
tttgtataat ttaaaacttg atgacattaa ctttgagaaa cgtgagtgct tactagaccc 2040
ttgggatgtc cacactgact ggtaccgagt agtgtactgt ctctgagctg ttttcatttt 2100
gatttgaata ttaagcagat ggcttcttga gatagacccg tgccagaaca tgccagggat 2160
aggctgaaga aacgggccag atgatacaaa tttgtgtggt caccatccat gagagaccag 2220
ggacactggg gctgatgatg acctctgcaa ctctgaagca aaagtaaact aattggcaag 2280
ttgggtgcgg tggctcactc ctgtaatccc agcactttgg aagctggggt gggcagatcg 2340
cttgaggcca ggagttcgag accagcctgg ccaacatggt gaaaccttgt ctctacaaaa 2400
aaatagaaat attgcctggg catggtggcg gacatctgta atcccagcta ctcaagaaac 2460
tgaggcagga gaatcgcttg agcctgggag gtgaaggttt tagtgaactg agattgtgcc 2520
actgcactgc agcctgggcg ccagggcgag actccgtctc aaaaataaat aaataaaata 2580
aaattaatta actaattgac attagaaaaa aatgtttttt ctttcttttc ccacatcctt 2640
tttttttttt tttttttttt tgtgacagag ttttgctctt gtcacccagg ctggagtgca 2700
gtggcatgat cttggctcac cgcaacgtcc acctcacgga ttcgaacaat actcctgcct 2760
cagcctcccg agtagctggg attacaggca ctcaccacca cacccggcta atttttgtat 2820
ttttagtaga ggtgggtttc accatgttgg ctgggctggt ctcaaactcc tgacctcagg 2880
tgaaccgcct gccttggcct cccaaagggc tgaggttaca ggtgcgagcc accgcgccgg 2940
gcccttttcc gacatcttaa acgtaaagta ggagacgtgt cataatcatc gaatactgca 3000
gtggttttca ttagctcctg tttgtcaaac ttatgaacag agttttaaaa attgtgtatc 3060
agccgggtgc ggtggctcac acctgtaatc tttgggaggc tgaggtgggc agatgacaag 3120
atcaggagtt tgagaccagc ctggccaata tggtgaaacc ctgtctctac taaaaataca 3180
aaaattagct gggcatggtg gcgggtgcct atggtcccag ctactcagga ggctgaagca 3240
ggagaatctc ttgaacccgg gaggtggagg ttgcagtgag ctgagatggc accacagcac 3300
cccagcctgg gtgacagagc aagactccgt ttccaaaaaa aaaaaattgt atatgagaga 3360
gacagaacta gacagagaag aaggagaaaa tgtgtcttct ttatacacta ttttgtaact 3420
tgctttatcg agtaggttat gaaaaatctt cctatgtgaa aaacatttct gcatcatttg 3480
aaatgtctat ataatatccc attgtgttta gatacaataa tatttagcca atctctttat 3540
gtgtatatat ttaatacagt cattctataa atattgactg agtagctgct gtgggctact 3600
gtccgcagtg ctgaacaaga caagcatgaa tccatgaaac tgattttcat accagaatat 3660
aaaaaagaaa cttaaagata atcctcatca tggtaaaaga tgaagaacct atttttgccg 3720
ggacatctta ctctttagta attggtggcc agtgttcttt ttcttgcatg ctgttttgga 3780
gagtctgttt tttaaataaa tatttaagta gcctgggcgc agtggctcac gcctatggtt 3840
tcagcacttt gtgaggccga aggggatgga ttgcttgagc ccagggcttc aagaccagcc 3900
tgggcaacct ggcgaaaccc tgcatctact aaaaatacaa aaattagcca ggtatagtgg 3960
cgtgtgcctg tggccccatc tacttgggag gctgaggtgg gaggatccct tgagcctgag 4020
aagtggaggt tgcagtgact gagatggcac cactacactc cagcctgggt gacagagtga 4080
gacctggtct caaaaaataa ataaatattt atgtaatcat ctttaagcag tgtttttaat 4140
tttatttatt tatttattta tttttgagac agggtctcac tgtgtcacct aggctagagc 4200
acagctgcat gatcacggcc tattgcagcc tcgacctccc tgggctcagg tgatcctccc 4260
acctcagcct cccaagcagc taggaccaca ggcacacgcc accaggcctg actcattttt 4320
gtattttttg cagagacggg gtcttgctat gttgttcaga cctgtctcaa actcctgggc 4380
tcaagccatc ctcctgcctc ggcctcccat agtgctggga ctaagccatg aaccactgca 4440
cccggcataa gtggtctttc tttaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4500
aaccacatta attaaaatat gtatttgctt attataaata tatttgaaac atgccaattt 4560
ttcttctctt tttttgctct attggtttct gtgtgtggat ggatatattt ttaatggcaa 4620
ataggatgag tgtctttact tccaagtagt cagtgttttt ctttaatgtt tgtactaatt 4680
ttgtcacatt gcagttagag gttgtggcct gtctaatttc tgcttttttg gaacttgaga 4740
gtctctgttt ttatttgttt ttggtagcct ggcatagagt ccatttttct tttcttttct 4800
ttttttgaga cggagtttag ctcttgttgc ccagactggc gtgcagtggc gcaatctcag 4860
ctcactgcaa cctccgcctc ctgggttcaa gcgattctcc tgcctcagtc tccccagtag 4920
ctgggattac aggtgcccac caccacacct ggctattttt tgtattttta gtagagacgg 4980
ggttttgcca tgttggccag gctggtctcg aactcctgat ctcaggtgat ccacccgcct 5040
cggcctccca aagtgctggg attacaggtg tgagccactg cgcccagctg tagatacttt 5100
ttaaaaaggt atagtttctg attatggggt agaaatgtgc tatgtctgtc atttcagcct 5160
tatgaattgc ccagaataag ctagatcacc tttaaggcca tgtggttagg gaaacttggg 5220
cacagaattt acattttcaa cttggtgata agatgggttt aaggtaagaa tcaaatagga 5280
gaaagcctta gctgttccag cggcccatgt ttaaaagaat gtgcttcttt ttccaagtat 5340
ttctgccgct tgcatgcact gagcttcttt ggaaaggagc accatgcagg catattttcc 5400
agacaggacc ggatttgctc gttactcaga ggtgtgtgca ttctttgctt ttaggatatt 5460
taattagcat cttttaatag tgatattacg gtgtcttaaa agtttatgca tttgaaaaga 5520
aaagaactta ctccttgcca ggtctcaacc tatcatggtt atctttgcag ctgagctgcg 5580
ttggttttga ggctcacata tggtaaaagt ggttggaaat ctggaaatat tgctgtgtat 5640
ctgcaaagca gcttgatata gtggaaaagg tattaggtca ttaatcatga gatttggatt 5700
ctagcccctt agctgctgcc tgccaggcct ggagaccttt gttctcttct ttaaactgct 5760
gctttctcat cagaaaatga agttcctctc cataccacct ctctgaaggg ctgtgaagct 5820
cgaagtggca gcttaaaaaa ctgcccatct caggaggtgt cttaagaagg aggacatacc 5880
gctggctcct gcctttctca cttagccagg tctgatacct gtgttgtttt cactgtggcc 5940
attttaggat ttttcaaagg ctttcagaaa gcaacatgct accgtacccc ttatacacca 6000
aaactggttt tcattttgga atataaaagt gagatttctc caccagtaca ataaagttgt 6060
tacaagtggt tcctatgtgt ttgtttttgt ttttgagaca gagtctcact ctgtcaccca 6120
ggctgcagtg cagtggcaca atcttggctc actgcaacct ccgcctcccg ggttcaagca 6180
attctcccac ctcagcctcc taagtagctg ggactacagg cacccgccac cacgcccagc 6240
taatttttgt atttttagta gagatggagt ttcaccatgt tggccaggct ggttttgaac 6300
ttctgacctc aggtgatcca cctgcttcag cctcccaaag tcttaggatt acaggcgtga 6360
gccaccacac ccggcctcct gtgtgttttg aaggtgattg tgacctcagg ttttggcagg 6420
gctatacctt gtgtttgctc ttactccaac tccatggcat acctggacca ggcctcttca 6480
tcttgaagag ggatctgctg aaatgcaggc ccagtgaatc tccccatgcc tggacacagt 6540
tccgtcaagc caggacccgg tgctgcctgc acccctgttt ctgttagtct gactgtcctc 6600
gctgagtcta actccttgag ggcagagagg atgtcttatt tatttctgcc ccgctagccg 6660
tgtaaactga gtaggtactt gtaaatgttc attgaataag tacctgatta atagaattta 6720
attcaagaag aatgtattga tgggcctgtg tggtcaccac agtactgaga tgtaggtggg 6780
agctggctga agggggaggc acctaaacag gagtgcagac agcggcacct acggatgatg 6840
gcccgctcca tcccaccgca gcgaaattgt cccagacctc tgcagcttcc cccacaccta 6900
gactgagaga gagctcttct tccttctgta gggagcaggt gtttcctcca gatgtccaat 6960
atgtacctcc cattacagcg gtgttaggaa ggtgagggct gccgctgaaa gggtcccctt 7020
cataatcatc actagatttg gggtatatta tggattaaat agaattttta taagatgacc 7080
tgaggatcta tttaaataaa atcctctttc tttctgcaag atcatggatt taaattcaac 7140
acaactgact tcatagggaa ggggtatggt gaaagggaag tgaggtgggc agcactgata 7200
tttaacaagg tgagggtcct tctcctgctc tgactgtcac attaaaatat tcccaggaga 7260
aattggagaa aactcagatg aaatatcgtc tgtgttccag gaggcaggac tcatcggaat 7320
gcttttattt tgctccattt taagagattt gcagataaag aggagtgaag atttctattc 7380
agatttactt gctttatatt ttaacttata gaccacaagc caactttcga aagagcatca 7440
ttttgaatag taagagttag gaaggcaaat acagaaggac taatggcttc caagattatg 7500
agcttcatag gaatggtttg agatgaggct atagtaaagc agaatattga agttccccca 7560
ccccctttca tttttcattt ttcattttta agagtgagcg aggccaggcg tggaggctca 7620
cacctgtaat cccagcactt tgggaggccg aggtgggcag atcacaaggt caggagtttg 7680
agaccagcct ggccatcatg gtgaaaccct gtctctacta aatgtacaaa aattagccag 7740
gcttggtatc aggtgcctgt aatcccagct actcaggagg ctgaggcagg aaaattgctt 7800
gaacccagga gtcggaggtt gcagtgagct gagatcgcac cactgcacat ctcagaaaaa 7860
aaaagagtga ggccccaagt ttttttgcat ttgtttgtaa ctgaatacgt ctgaagttat 7920
gtgataacca cgccaaggtg acaaattgcc aagtttcagt aaaagagacc cagttattta 7980
gaggttgaca cgtggatatg tccctttcta agaagttcgt ggtcagcttt acatgagtat 8040
ttaaatgcgt gtttataatt cagcaatatg gcttgtaaaa tacagattgc caatcaagtg 8100
acatgcaaat cttgatgatc tgaaacaagt tttcttctgt tatctatgga agaaatggta 8160
atagggatat ttaagtggga tgaatttttt gaagcatttt caggcagttt tccacatgga 8220
acaaaataac attgagtggg ctgctaacat gaggaacata ttgccctctg cctaggatta 8280
tgagtaaatt tgataaattc tagactgcag tctcatttta gctcatttta tgaggcagct 8340
tgacaactgg gatagtgtct cttttttttg tcgggggtgt tgaggctgga gtctcgctct 8400
gctgcccagg ctggagtgca ctggcgtgat ctcggctcac tgcaacctct gcctccgggg 8460
ttccagtggt tctcctacct cagcctcctg agaagctggg attgtaggca tgtgccacca 8520
cgcccggcta atttttgtat tttttagtgg agacgggctt tcaccatgtt ggccaggctg 8580
ggtctcaaac tcctgacctg aagtgatctg cccgcctcag ccaccctaag tactgggatt 8640
acaggcatga gccaccacac ctggcttctg ttctatctgt gcattgggga tgaaattaac 8700
acaaatgatg tttaaagaaa aaaatgctca gagaagttag aaatgtgctt taaattggaa 8760
tcatctctta gtatgtaaaa gttttttgta atagaaacaa gcagggcagt atttgacctg 8820
ttgacagtgt ccttggactt tacaatttgt gaagcagcgt attttgcttg agttgtacga 8880
ttgtcgtttt tttcccccca ctttgacaac tgttacagaa cctgtcacca gatacaggca 8940
agggaggttg ggcttcccat ctctgcacgg cttccctgtg attcacaagc aagcaatcag 9000
aagtgcacaa aagtttagaa cgcgattttc attctcttct ttccttagaa aaactcgctt 9060
tgttagcctt ttccagaaag gaaggcactc aattgttgta atactcaaat cataaaaaga 9120
agcctagtct agtctattca gcaaggtgtt ctgaaagagg gaatttttta agttcaatta 9180
tgcgaagatc ttgaaggtgg gactcaaagg agagggctat cctgggaaga aggctttgga 9240
aaatgagagg catgaagggg agagggtatt taaatgtgtt tgaagccaag gatccttgag 9300
agaaaaagct ggcactaaca gcgttcaaag aacttgcgtg acaagtgatg actaatgaca 9360
ctgagggtgg gttgtgggtg cctagtgaat tcctccgaag ccaagagaga ggtttccaga 9420
cccagggaag aaggtgtgta cacccagaag tagtgtaggg acagagattc cgatcacaag 9480
ctgtgactgg aagacgccga ccaccactgc agcagcctga aaaccacagt cttgaaccgc 9540
cagcgaaggg ctgggaagtg cggatccagg gctggtgcac tgaacccaga ggagcaggct 9600
cccattccca gctaagggtg gcagctggcg gggatctttc cagcagaaag ctgtaagtgg 9660
aagctttcaa ttcagagcag tagcaatgcc ttcaaagtcc caggcttcac gtgggaacag 9720
agaatgtgaa gagtatttag caggatgcca atataagaaa tctatattgg tgttcgtttg 9780
tttgtttttg agatggagtc tcgctctgtc acccaggccg gagtgcagtg gtgcgatctc 9840
agctcactgc aatctctgcc tcctgggttc aagcgattct cctgcctcag cctcctacat 9900
agctggtact acaggcacgc gccaccatgc ctggctaaat tgttgtattt ttagtagaga 9960
tggggtttca ccacgttggc caggctggtc tcaaactccc ggcctcatga tccgccctct 10020
gcagcctccc aaagtgctgg gattacaggc gtgagccacc gcacctggcc caatattgtt 10080
tgtttattta tttcttgaca ggatctcact ctgtcaccag gctggagtgc agtggtgtga 10140
tctcagctca ctgcaacctc cacctctctg gctcaagcaa tcctccctcc tcagcctcct 10200
gagcagctgg gactacaggt gcacaccacc acacccaact agattttgtg ttttttgtag 10260
agatggggtt tagccatgtt cagctagtct caaactcctg ggctcaagtg atctgtccgc 10320
cttggcctcc caaagtgttg ggattacagg tgtgattcat gatgtccagc ccagtatttt 10380
tctttcactc tggaaaccaa aaattattgg ctttttttcc tgttgcattc cctttactta 10440
gatgaatcta gcaaggttgg ctgttagtgt ctaggtcaga agtctaagtg aaagtgaata 10500
tttaaccaca ctcaagcaca gctgatgatc tttaatacta atagaggtat aagacttaaa 10560
agaaacaaga acccagaggg aaaatatggc catggactca gagaaaacca cggcagcttc 10620
catggactca taaaaagagc tcaaaaccta ggaagtggat ggagactctt tttggaatga 10680
atgaattcaa atgtgggctt tcttagtaga ttaaatcatt ttctagaagg aatttcagaa 10740
ggatgtgtgc ccaattatgg tatcaggtct gttgtagact cttcaaggag gaagcctctg 10800
aaagacaaga aggaacaatt aaaaattaga attcaggtga gtggatcacg aggtcaagag 10860
atcgagacca gcctggccaa catggtgaaa ccccgtctct actaaaaata caaaatttag 10920
ctgggcatgg tatggctgta gtcccagcta ctcgggaggc tgaggcagga gaatcacttg 10980
aacccgggag gcggaggctg cagtgaacca agattgtgcc actgcactcc agcctggcaa 11040
cagcgagact ccatctcaaa aataataagt aaataaataa ataaataaaa attagaactc 11100
agaaaaggaa ttaatttctt ctgagagaga aaaagatgag attctagcct aaggtgtaac 11160
acatccatcc accaggtatc atttttatac acgtgaagtt aaatcaccaa aggaccaggt 11220
gagcagatgt ggactttccg actgtgtgtg tgcgacttcc tcagagccct cagtggcgtt 11280
cccttttccg cgctagcgtt tggtccctgc gcttttctgg atgcccccac cccctctggc 11340
tccacgaggc cccctgtacg tcaccatcac ctttgtgagc ttgaaacctg tcacccaccc 11400
gccttccaga tgtcacctgg gccctcccgg aggccctcgc cctcagtgtg tctgattctg 11460
agctgtcctg cgttttcccc tcccctcacc ctggcgaccc ttttcggtct cagttgccag 11520
cctcctgcta gggctgggtg ggggacatca aaggcaggac aaggtgtagg gtcctcaccc 11580
accacttagc agctctcaga tgcagacaga tttttcagct ggcctgtggc tcagtttccc 11640
tcagctacaa gaggggtgca tgctagggtt tctctggatt gctgcacctg gcaggtagtg 11700
tgagcttggt aggtgcttcc ttgcttatca ttgcctctcc catcttaatg ttgtcccatc 11760
catccaatgt ttatgggatg agaggttgat aggagggcat ggccctgaca ttccagggac 11820
tgaccgacac gctgtctaca caaacccctt ctggttcttc tcgtgcactg ggcgtgccgg 11880
agacacactc ccttaccctc ataccccgcc gcacccctgt gacctctacc tttgagacct 11940
cagcttaaac tcactcttag ggaaggctcc ctgaaccacc tgctggggtt gtatgctgat 12000
gcaggtactt gtaacacctg gtgcttttcc tttcgtgcac tcaggcagtg tttattcaag 12060
tgatggcttg gtgacagtgg ctctccctga gaccccgtga ggccagagtc cttggctcat 12120
cactcatggt tgaacccgga gcctcttgct ggtaggtgct tcaggactgg ctctgggagc 12180
ctgtggctcc tgccgggtac ccaccggttg agatacctca agttttaaat gccacctcct 12240
tcctgaagcc ttccttgctg ctcccccaaa ctagaggcag gagttttgtc cttcagataa 12300
cctatggcat ttgagtcact ctgatttgat gaattctgcc ttcacttgag cagctattag 12360
gggcatatgt cagtcattca ttcctcagtt catgtattta ttcagcaaat atttactgag 12420
cacgtactgc gtgccaggca ctgtcctgct gtggaaaaca gcaggcatga ttccctgcca 12480
ctaccaacca ctgcatcgca taactggcag actcccagct tcaaggagag gcacggaggg 12540
aaactgagag cagcctgcag aggggaaaga gcggggacag agggtcacgg aggtcgcagg 12600
ggcgtgtgtg cagcacctgc cagtgaacgg aatgtgcggc tccagatgtc gttgtcttta 12660
aacttcggaa tttcctttca ctaaagaacc aagtccaggg ggaggaaaga gtgaatacaa 12720
attatccaag aaactcaaga gctcatttta gttctcctga ttatgatctt aaaggcatta 12780
agcgctcaag ttaaactcct tgtgacccac ataggttagc agaatttaaa tcctaggtga 12840
ttattaactc taatcataca tctaatgacc tatattgaag atacactgcc tgcttagttg 12900
tggcttcagc ctttgctccg tcactgatag ttctagcctg aaaagcaaat gagccctcat 12960
gctcacgatt tcaccacagt cacataagcg ggaagagcag gctcctggct gtggcgagct 13020
tgactccatt tggtttgata gaaatgagag gtagatgatt ccctagacaa atgcaggcct 13080
ttctcgaagc ccctttccca ggacgacgtg acatgagtgg tctgtgcctt ccagggcagc 13140
cacgtcatgc tttgcccagc cagggcggtg gggagggaga cagccacatc ctgcccgggg 13200
ctcctgggcc ccgctgcatc aagtgaaagc agggctggct ccctgatgtc cttggagaag 13260
tcgcccacac tgctttcccc catgggagtg acaaggatgt gtcccgccag ccttccacga 13320
cggacccccc actctctatt aattcccaag aaaccaggcc atggaggtgg gtttgagggt 13380
ttgtattggt gttttttaaa gtcaggttga ccgagtgcgg tggctcacgc ttgtaatccc 13440
agcactttgg gaggctgagg cgggcggatc acatgaggtc aggagttcaa gaccagcctg 13500
gccaacatgg tgaaaccttg tctctactaa aactacaaaa aaaattacct gggcgtggtg 13560
gtgggcgcct gtaatcccag ctactcagga ggctgaggca ggagaaaccc ttgaactagg 13620
gaggctgcag tgagccgaga tcgcgccact ccagcctggg tgacaagagt gagattctgc 13680
ctcaaaataa ataaagtcgg gtttattaag atataattta catacagtaa tttttttttt 13740
ttttgagaca gagtttcact cttgttgccc aggctggagt gcaatggcac gatctcagct 13800
cactgcaacc tccgcttcca gggttcaagc cattctactg cctcagcctc ctgagtagct 13860
gagattacag gtgtccacca ccatgccttg ctaatttttg tatttttagt agagacaggt 13920
tttcgctatg ttggccaagc tggtcttgaa ctcctgacct caggtgatcc gccagcctcg 13980
gcctcccaaa gtgctgggat tacaggcatg agccactgca cccggccagt acatgctttc 14040
ttgatttgtc tgtttcccac ctgtctcccc tccctagaat ggcagctcca tgacgacaga 14100
ggtgtttctc tgttttctcc atggctgcac cctcagctgc tagaaggtgg cccagcatag 14160
gaggtattta atgaagcctt cctctccact taaatctaca cccttgtgct tattaaaagg 14220
tgacagtttt ctgtttgaaa attttattag tgttttaatg agaaagttat tatttgggta 14280
atgcctgaat atgaggaaaa cattaagggt agaaatgtaa ttgttttcct atttcattca 14340
gtctatggat tttattgaag attacagaat tacttctttg tagctatgga agtaaaaaaa 14400
taataagacg agtagctatt tcaaaacgta gggctgataa atttgggatg gtttgagaac 14460
gttaagttgg ggaactccat ttcttttttt acatttttat ttattttcat ttgtttattt 14520
atttatttga gacagagttt cgctctgttg cccaggctag agtgcaatgc catgatctcg 14580
gctcactgca acctctgcct ccggggtata agtgattctc ccatatcagc ctcccgagga 14640
gctgggacta caggcgcctg ccaccacacc tggctaattt ttgtattttt agtagagatg 14700
ggatttggcc atgtcagcca ggctggcctc aaactcctga ccgcaggtga tccgcctgcc 14760
cttggcctcc caaagtgctg ggattacagg tgtgagccac cgcgcccagc cagggaactg 14820
catttctgac agtggctcag tagtttggaa gttaactggc aaaggtggac agaatcttta 14880
aacatatgtg gaggaattgg agagtttaca agatagtgaa gaactgccag gccatggtct 14940
ggagaagatg gaaacttgat gtttggggcc attgtgtccc tggggtgttg gccaatttat 15000
gaaagaagca gttaagagcc tgagtggcac ttttgagggg ctagaaggga agaccctggt 15060
aaacatccca aactttggat tgggacccaa aaaagctcca tcccaggagt acaggtgacc 15120
tggaaacgga tcagcgtaat cgaggactga agtccagttc tagctacgcc cagtccttga 15180
gactggatta aggtgatctc agattgcaag gacctcaaat gcctggcaga agcaagtgaa 15240
tatccttctg gaggaacaga gcctcatcct aggcctctaa ttatttttaa ggacaatttt 15300
tcaaatgcag gctttcctcc ctttgcacag ttcccttatg cataaatttc agtcagtggc 15360
cagctgcagt ggctcatgca tgtaatccca gcgctttggg aggccaaggc gggtgaattg 15420
cttgagtctg ggagttggag accggcctgg gcaacataga accccatctc tatttttaaa 15480
aataaaatat taattatcac tgcttagtta aattatagtg gtctcccaac aatacagatc 15540
agatcccagc tcccatggta tatacactgt gagtgctgta taaagtacaa gctctgccgc 15600
cagttctcca gcctacaaat cacagtatag ataacagatg tgcatgatga tcactggcca 15660
attgcgtcac ttctctcaaa gtcagtctgt gattggtccc tgagcatctg tcggtcagtt 15720
tcatgcacag actgcaaagc atatggtttt gtctactctt tgtctctcag tgataaaccc 15780
acatggcatt ttgtaaaagt ggatacatca ggccaggtgt ggtggctcat gcctgtaatc 15840
ccagcacttt gggaggctga ggcaggtgga tcatttgggg tcaggagttt gagaccagcc 15900
tggccaacat ggtgaaaccc catctctact aaaaatacaa aaattagctg gatgtggtgg 15960
caggcgcctg taatcccagt tactggggag gctgaggcag gagaattgct tgaacccagg 16020
aggcagagct tgcagtgagc cgagatcatg ccactgcact ctagcctggg tgacagagca 16080
agactaccat ctcaaaaaaa aaaaaacaaa aaacagtaat caagcatgaa aattatgaaa 16140
tgctcagaga taaaatgcgc gaggcctgta cactgtaatc tacaaaacac tgctgagaga 16200
aattttaaaa gacctaaata aatggcaagt tataacatgc tcttgaatca gaagactcag 16260
tatcttagga tggcgacttt tcccaaaatg atctacagat tcaaagcaat cggaatcaga 16320
cctcagcatg cctacttgta gaatttgata acctgattct aaagtttata tggaaatgca 16380
aggaacccag agttgctaaa ataactttga aaaagaacaa cacagttgaa ggacttagac 16440
tacatgattt caagaattat tataaagcta cagtaatcaa gacagtatgg tattgatatg 16500
aaaatagacc attagatgaa tggaacagaa tagcaagtcc agaaatagat ccacacatat 16560
atggtcaatt gattttcagc aaagtgccaa gtcatttaag tggggaaaag ataatctttt 16620
caacaaatga taccggaaca actggatagc catatgcaaa agaacctcaa ccttcagctc 16680
acagcactac aaactcataa ttattatcat tatattatac tattatgtaa taatagtata 16740
tatcatgtta catattatat tatgtaatat atattatatg atactgttat gtcatataat 16800
tattattgaa atgggtcata gatctaattg taagagttaa aaccatccag gtacagtggc 16860
tcatgcctgt catcttgcac tttgagaggc caaggcgggt ggatcacttg gccccaggag 16920
ttacaagacc atcctgggca acatagcgaa acaccgtctc tacaaaaaaa tgaaaaaatt 16980
agttgagcat gatgacactc acctgtagtc ccagctgcac agtagtctga ggtgggagga 17040
tcacctgagc ccagagaggt caaggttgca gtgagccatg attgcaccac tgcactccag 17100
actgggtgac agagagaccg tgtgttaaaa aaagagttaa aactataaaa ccttcagaag 17160
aaaacatatg agaaaattct agtgatttgg ggtttggcaa agattccttg aacatgattt 17220
aaaaagcatt aactaggcca ggtatgctgg cttacacctg tcattccaat gctttggggg 17280
accgaggtga gaggatagct tgaggccagg agtccgagag cagcctgggc aacataacaa 17340
gagtgggtct ttaccaaaaa aaaaaaataa aaagcctgtg ccaggcacag tggcacatgt 17400
ctgtagtcct agctactcac gaagctgagg caggaggatc acttgagccc aggagttgaa 17460
gcttgcagtg aattatgacc atgccactgc actccagcct gggccacaga gtaagactaa 17520
gactcagtct cttaaagaag aaagcgaccg ggcgcagtgg ctcacgcctg taatcccagc 17580
actttgggag gctgaagcag gtggatcaca agggcaggag atgaagacca tcctggctaa 17640
cacggtgaaa ccccatctct actaaaaata caaaaaatta gccggacgtg gtggtaggcg 17700
cctgtagtcc tagctactcg ggaggctgag gcaggagaat ggcgtgaacc tgggaggcgg 17760
agcttgcagt gagccaagat cgtaccactg cactccagcc tggacaacag agcgagactc 17820
catctcaaaa aaaaaaaaaa aaaaaaaaaa aaagaagaaa gcataaacta taaaagaaaa 17880
aattaataaa ttagtcatcc tcaaaattag aaacttttac tcatcagaaa acacttaata 17940
aaatgaaaag tcaagccata gacttagaga aaatatttac aaaacatata tctgacaaag 18000
gacttggata tggattatat aaagaactat tgtaattcaa taagatgtca aacaacccaa 18060
ttaaaaatgg gtgaaagatg aactaactct tcaacaatgg gcatgtcatt tgaatggatg 18120
gtaagcaagc acatgaaaag atgttcatgt gcctttccct cattagtcac tagggaaatg 18180
caagttcata gacatctctc ttcgtagaaa gatatcacta cacacccaca agagtggctg 18240
taattaagca gtctgaccaa gtatgcgtaa gaatgtggaa taagaactct catacactgc 18300
tgatgggaat gtaaaatgat agccactttg gaaaacattt tggcaaataa taccacttac 18360
attattatcg aaaatattgt atacctgaaa gaactcaaag tgaaaaagct atatactgtc 18420
tgcttccaag gctacacatt atgggaaagg caaaactatg aagacagtaa aaagatgcgc 18480
cagtggttgc caggggctca tggggaggga aagaggaatg aataggtgga acacagggca 18540
tgtttagggc agtgaaacta ttctgtatgg taccgtaacg atgaatacat gttattaggc 18600
atttgtcaat acccataaaa tgtacaacac aaagagtgaa aatgaaaact gtgggcttca 18660
gttagcaata atatgtcaac attggctcat cagtggcaac aaatgtacct caccaatgca 18720
agatgtttgt ttgttgtttg tttgttttgt gacggagggg gtgcagtggc gcaatctcgg 18780
ctcactgcaa gctccgcctc ccgggttcac gccaatctcc tgcttcagcc tccggagtag 18840
ctgggactac aggcgcccgc caccacgccc ggctaatttt ttgtattttt agtagagacg 18900
gggtttcacc atgctagcca ggatggtctt gatctcctgc tgtcgtgatc tgcccgcctc 18960
ggcctcccaa agtgctggga ttacaggcat gagccatcac gcccggccac caatgcaaga 19020
tgttaataac agggaaactg tggtgggagt gaggtggtat atgagacctc tctgtacttt 19080
ccactcaatt tttctgtaag cccaaaactt ctctaaataa gaaagtttat taattaaaag 19140
ttacttttat agtgtatcta tatctaggaa taaatctgaa aaagatatat aagatctcta 19200
ctcagaaaac tgattatgtt attaagagag cttaaatata gcccaaataa atagatggat 19260
atactatgtt catggaaggg acagctcagt attaggaagg tgtcagtcat cttaagaaaa 19320
gcctcatgtg tcacacaagg gatactgaca tctgacacca agcacatgta ggcatcctga 19380
ctacgtttac ttgaatgatg tggactttac agagctgact atagacagtt caaatggcct 19440
gaaaactgtt caatgcactc cctcccaggc tgtcatggga tgcacttcag gaactttact 19500
ttttaacaag aaaattcagt tttcctctta aacagctggc ttctgttcca ttagcattct 19560
tgtcacttta agttgcattc atctttgttt ttttttttta gaaaaacatt tgttctgcaa 19620
ccagtcttgt cctttaaata cttgtactgt atacaggctc tttttcatag gtccattact 19680
taaaatgatg taagtgtgtt tttggtggca ggggggtggg agttgtttgt tttgttttgt 19740
tgagacacgg tcttactctg tcacccaggc tggagtgcag tggtgtgatc ttggctcact 19800
cctggcctca agtgatccac ccacctcagc ctcctaagta gctgggacca caggtgtgta 19860
ccaccacacc cagctaattt tttttttttt tttttttttt ttttgtaggg acggggtttt 19920
gtcatatcac ccaggctggt ctcaaactcc tggactcaag ggatcagcct gtctcagcct 19980
cccaaagtgc tgggattaca ggtgtgagcc actgcaccgg tcctgatttg agtttttgta 20040
agacagggaa caatgttcag aatttagcac caatgtcaga ctcattctgt aaatttttat 20100
tgaacgtctg cctggtgtag gagaggaaga tgacagacaa gaattcttcc tccaagagtt 20160
acaggtcagt tgagcagaaa aggcatacat caatacccac aatgagagtt gtcgtgattc 20220
agaggaggga caaagtcctt cccctggagg gatcctgagc actttggaga ggaaaggcat 20280
ctgtactgcc ccccaaatgt gtagaatggg atgcattcct ggcagaaaga agtaggataa 20340
agtacagagg ccagggctgg gtgcagtggt tcacgcctgt aatcccagca ctttgggagg 20400
ccgagacagc agatcacctg aggtcaggag ttcgagacca gcctggtcaa catggcaaaa 20460
ccctctctct actaaaaata caaaaattag ccaggcacaa tggcaggtac ctgtaatccc 20520
agctacttgg gaggctgagg caggagaatt gcttgagccc aggaggcaga gatcgcagtg 20580
agccaagact gcgccactgc actccagcct gggcaacaga gcaagactct gtctcataaa 20640
aaaagaaaaa aaaaaagtac agagtccagg aagcctgggg tggggctggc agatgccgag 20700
tcatctattt tggccagagt tcaaggcttg ctaggggaca tgaagagaag attcgtgcat 20760
tctagttcaa actccaccag atatttgagc tccttctctg taccaggcat tgttctaaga 20820
tacgtaagtg aacaaaaccc atgacaccct cgtctatgag agctgatcct ctggcaggga 20880
cagacaggtc atgagtggag tgatggagca gctggcctgg tgacttagcc gccttcaggt 20940
acagtaggag gagcaagccc aggacaggtg agtgggtcaa gggtgccaga aggggtgagg 21000
gcaccaggaa gctggtccag tttggcttcc ctgaggtggt gaccaggacc tagcatctga 21060
ggaagggctg gaagcaggtg agagcaggtg gagcagacat caggatggga gcatcctgac 21120
agggagggca gcagggtggg ctcatgagag gaacagccag gaagtgtgac tcgagcagtg 21180
tcctggagag gaggaggagg agaaagaggt caggaggtcc caggggagag gcaggaccag 21240
tctcgtggag gtcggggccg ttgtgaggac tctggtttgt gttgtgtgtg aaaggccatg 21300
ggatggggac cagcgagggc ttcttagggg actggatatg ctctgatcta gctgctaaaa 21360
agcccccttg ggcagcttgc agggcccggg cagaagctat aggtggttct gaggtttgca 21420
gaggggcctg aaggggtggg gcccggccaa gcaaggtggc taagtgggaa aggctccacc 21480
gcgttgggtg taggaagacc ttgaccttag ctccagccca gccactgagc agccgtgtcg 21540
ccttgggtga tacctgtccc tggtcggttt ccctacctgt gaatctgggt acttggaagc 21600
catgctcgag aagagcccat ccccaggagg tgatcagggt tctccttcag gtgaggaacc 21660
tggcagccgt gtgtgagaac cttagaaaag ggagagggaa gaggctgtgg caggaagtga 21720
ggagggagtt agtgataccc tgggcaggat gccatgagct gggatggaaa ccacaggatg 21780
aatgcaagta attaaaaaaa aaaaaaaaaa aaaaacagca ttgggccggg cagtggctca 21840
cgcctgtaat cccagcattt tgggaggccg aggtaggtgg atcacctgaa gtcaggagtt 21900
ggagaccagc ctagccaaca tggtgaaact gaaaatgcaa aaattagcca ggcatggtgg 21960
cgtgtgacta tagttccagc tactcaggag gctgagacag gagaatcact tgaacctggg 22020
aggtggatgt tgctgtgagc tgagatcgtg ccactgcatt gcagcctcgg tgagagagca 22080
aggccccatc tcaaaaaaga aaaaaacaga ctttccgacc aaacgatcga caaaccagac 22140
tgtccaaaca gccataagcc gtaactttgt gcggaggtaa aagaccgagg tcacatcggg 22200
acctgttgga ttcaaggcat gttgacagct gtttccaggc ttcagataga gcctccagct 22260
ggcagggtgg ccacagggct tgttgagtag gaagcctcgt tgctttgaca ggttacttgg 22320
ccccatgagg gacaatccca tagtcagtta cccagaaacg tgactgtctc cttgaaatcc 22380
tcagcatggg gtcttatgaa taaaccctta ctagatttcc tgttctgtct tatttttatg 22440
cagagcttta ctttatagca gaaaattcca tttttaccct taaatggctt gcttctgctc 22500
ccttagtgtt cttgtcactt taagttgcat tcatctttgt ccctttagaa aaggatttgt 22560
cctgcaacca gctcttgcag aaggtacttg gtttattgtt aaccgatgtt tgctaaatgt 22620
ttgaattatg ttgagttgct taaagtcatg ctatcgggta gatgttgtgg ctgttctttt 22680
cactctctta tttggggatt tacaaaacag ttatgttttt agttttcttt tatttgttgt 22740
gttgaatagg aatgtagctc tgggaacctc tagttccaaa taagaaagcc ttggacacat 22800
ttccagttgg caagctggca aaatgaaggg cgtacaagtt gttagagagg ctgggagcct 22860
atttaagcac ccagcttcag gatgggacat gggatatacc tcgagttaga ggttcttatt 22920
aactgtggat tcttctatgc agatatctgt cacaatataa gttactataa gtcagtacta 22980
aggcagctgc tacattctgt ttgccaaggg gaagaagaaa gcttggaaat ggtattcctt 23040
aaaaatgtca gtatcataaa agacaaagaa aagctgcgga aatgtttcag attaaaagag 23100
agaagacaat aaaatgtaat acctgactct gaacagcatc cagtactgaa ggaggaaaaa 23160
tgctatcaag gacattattg ggtcaattaa caaaatttga atacgaatca tagattgaac 23220
tgtatctgtt aaattaacag aagcgaagtg ttctgtggtg tgtaggagca cactgccatt 23280
cttagcaaac gtgtagttta gtatttagga gaaagggcca tgaggcatgc aactcaccct 23340
caaatacaca cacacataca catatataca tacataccta taaagaaaga aattatgggc 23400
taggtgcagt ggctcatgcc tgtaatccca gcactttggg aggccgaggt gggtggattg 23460
tgaggtcagg agatcgagac cctctctact aaaatacaaa gaattagctg ggcgtggtgg 23520
tgcacgtctg tagtcccagc tactcgggag gctgaggcag gagaattgct tgaacccagg 23580
aggcagaggt tacagtgagc cgagattgca ccactgcact gcagcctggc aacagagcaa 23640
gactctgtct tgaaagaagg aagaaagaga gagagagaga gagagagaga gagggagaaa 23700
gaaagagaga gagaaagaaa gaaagaagga aggaaggaag gaaggaagga aattatgata 23760
aagcagatgg ttaagttggt aactaccagt gaatatgggt aaagttagga tgttctttac 23820
tctgttttgg gggtgcaact tttctataag tgaaagtact tccaaataaa aagttaaaag 23880
gcaagcaaat aaataaaaga gacagtttct atgttatata tcctagctat gtttaccatg 23940
tctggattct gaaagctgca gagcagaaaa cctgaagaac agatcacctg ttcttaaaat 24000
accactgttg gccagacata gtaactcact cctgtaatcc cagcactttg ggaagccgag 24060
gtgggaggat cacctgagct caggagtttg agaacagcct gggaaacata gtgagaccct 24120
gtctctacaa aaatttaaaa aattatccag gcatcatggt tcgtgcctgt agtcctagct 24180
actcaggagg ctgaggtagg aggattgctt gagcctggga gttcgaggct gcagtgaacc 24240
atgatcacac taaagcactc tagcctgggc aacagagcaa gaccctgtat caaaaaaaca 24300
atcaaacaaa aaatcactcc taattttcct cccttttagt acttttaaaa attaacttaa 24360
aacatttttt ggataattgt agtttttttt actttttttt ttttgagaca gagtctcatt 24420
ctgtcaccca ggctggagtg tactggtgca atctcaggtg actgcaacct ctgtctcctg 24480
gattcaagtg attctcctgc ctcagcctcc tgagtagctg ggttcatagg cgtgcaccac 24540
acctggctcg tttttatatt tttagtagag atggggtttc accttgttgg ccaggctggt 24600
ctcagattcc tgacttcaag tgatctgccc gccttggcct cacgtgcagt tttaggaaat 24660
aatacagaga tccccagcac tctttccagt tttccccaag ggtaacatct tgcaaagtga 24720
gaggacgata tcacagtcag gatactgaca ttgataccat caagatacat aatgtttcca 24780
tcaccaatca gtggtcatgg tgccttttat agccaaaccc acttctctcc taccttccca 24840
tccctttttt aattttgcca gtcattaatc tgttgcccat ttctgtcatt ttatgaatgt 24900
cacataggcc gggcgcggtg gctcacgcct gtaatcccag cactttggga ggccgaggca 24960
ggcggatcac gaggtcagga gatcgagacc atcctggcta acatggtgaa accccatctc 25020
tactaaaaaa tacaaaaaat tagccaagcg tggtggcggg cgcctgtagt cccagctact 25080
cgggaggctg aggcaggaga atggtgtgga cccgggagac ggagcttgta gtgagctgaa 25140
atcacaccac tgcactccag actgggtgac aaagcgagac tccatcttaa aaaaaaaaaa 25200
aaaagaatgt cacataatga atcatatggc atataaccgt ttgagactca gggtaattct 25260
catgagactc atccagcttg ttggtgcatc aacagtttat tcctttttat tgctgagtaa 25320
tttccatggt atggaggaac catggtttaa ctattcaccc attggaggac atctaggttg 25380
tttccagctt ggagttatta tgaataaagc tgctgtgaac atttgtgtac aggtttcttg 25440
gttttctggt ttgttttaaa cagttctagc caggcacggt ggctcacacc tgtaatccta 25500
acacttggaa ggctgaggta ggaggactgc ttgatcctag gaggcagagg ttgcaaggag 25560
ccgaaattgt gccactgtac tccagcctgg gcaacatagc aagaccctgt cattcatagg 25620
taggtggatg gatggatgga cggacggaca gatagatagg tagaaatgta aattacaggg 25680
ctacgctcag tggctcatgc ctgtaatctc agcactttgg gaggcgaagg cgggcggatc 25740
accagaggtc agcagtttga gaccagcctg gccaacatgg caaaacccca tctctactaa 25800
aaatacaaaa attagccaag catgctggca tgtgcctgca atcccagcta ctttggaggc 25860
tgaggcagga gaatcacttg aacccaggag gcggaggtta caatgagcca agatcatgcc 25920
actgcactcc agcctgggcc acagagtgag actccgtatc agtactttct ttttattgtt 25980
tttctgttat tatagtttaa gttcattgtt attagattat atactctgta tggcttcaat 26040
tcttttaaat ttgttgaggt ttgtttaatg gtcaaagaca tggtctgtct aggtgaatgt 26100
tccatgggct tttagggaaa aaagtatatt ctagtgttgt tgaatggtgt cttagtccat 26160
tcaagctgct ataacaaaat accgtaaact gggtgattta taaacaacag aaatttttct 26220
ctcacagttc tggaggctgg gaagttcaag atcaaagtgc cagcagattc agtgtcatgt 26280
gaggacgtgc ttcctgcttc atagataaga ggtacataca cgtttaggag catcgtgtct 26340
tcctggtgga tgaattctgt tatcattagg tgatcctttg agcactttta aaaagaatct 26400
gttggccggg cgcagtggct cacgcctgta atcccaggac tttggggggc caaggcgggc 26460
agatcacgag gttaggagat tgagaccatc ctggctaaca cagtgaaacc ctgtctctac 26520
tacaaataca aaaaaattag ccgggcatgg tggcaggcgc ctgtagtccc agctactcag 26580
gaggctgagg caggagaatg gcgtgaacac aggaggcaga gcttgcagtg agccaagatc 26640
acgccactgc actccagcct gggcaacaaa gtgagaccct gtctcaaaaa ataaaataaa 26700
ataaaataaa aataatctgt ttaatagcct actagtgttc ttcctttact attttattga 26760
gcattaatta atcccaacat tatgtctatg tcaggactga tgacaatatt tggtataaaa 26820
atttgatagt ctcagaggct gaggcaggag aatgcttgaa tccaggaggc agaggttgca 26880
gtgagctgag accgtgccac tgcactccag cctgggcaac agaacaagac tccatctcaa 26940
aaaaaaaaaa aaaaaaatcg atagtatcat atcctccagg attcaaagtg aacttcaaac 27000
agtcttatgt agtctaaatt ttggaatgca tcccagtatt gagttgcagc agggatttga 27060
gtttttgtga agagagagag gtatatcaga atcttgggca taaactaagg agccatgtca 27120
gaacctcagg tgtatgccaa tgagatagat cagaacctca ggcatgtacc cgatgagaca 27180
gatcagaacc tcaggcgtgt acccggtgag acaggtcaga acctcaagcg tgtacctgtt 27240
gagacaggtc agaacctcag gcgtgtagcc agtgagacag gtcagaacct caggtgtgta 27300
cccagtgaga cagatgagaa cctcaggtgt gtaaccagtg agatatatca gaatcttggg 27360
tatttaccca aagaggtata gcagagtctc aggtatatac tcaagaaggc atatcttgag 27420
gctttaagta tctagctaag gatttatatc aggatctcag gtttataccc agggaggtat 27480
agcagaattt ggggtataga tctaaggagg tctatcagtc tagagcatat agccaaggaa 27540
ctatatcaga acctcaggca cctacccaaa gaggcatttt aggactcgta aggagggggt 27600
agatttcaaa agtgtagtct aacagtttat ctactttgaa atttaaaaca atattaaagg 27660
aaaacatgaa atatttctat ctgtcagaag gtgacatgag ttttaaacaa ttaagaaata 27720
tactggctgt ggccttgtaa ccaaattatt atgcctatag aaattacaga ctccattttc 27780
caggatagaa taacagggac tgacttacct tctcatctga gataacaaaa cctccataca 27840
aatacatgaa acaatgttct tcaagatgct ggacatcagg cagtgaaggg cactgatggt 27900
tgtaagacaa ggtgagaggt gtggcttgag agagtttcca ggttgcagtg cagggagagg 27960
ggaaactgag gcagatcttg gcagacttcc tcagttgaca aaatagagct gagagtccag 28020
ggagaccatg gtgtatagat tatccaaagc aaagtatgag aggtgcaagc catatacaga 28080
gggactccag agatctacca aagtacttct tggtgcatcc atatgagcaa aactacttga 28140
ggccaggaaa agaaccatct gagaggatta gaaggaacag tgcccagtac ttgtgccagc 28200
caggaatggt gcctgatact cacgcagggc caggaacagt gcagggatgt gagtgtttgt 28260
taggagaggg aggtatatca gaatcttggg cataaagaca agaaaccata tcagaacatc 28320
aggtgtgtac caatgagata gatcagaatc tcgggtgtat acacagtgag atagatcaga 28380
atctcagatg tgtacacagt gaagcagatc agaatctcag atgtatacac agtgagatag 28440
attggaatct caggtatgta cccagtgagt ccaagagcat ggtgctggca tccggtgagg 28500
gccttcctgc tggatcgtga catgaagcaa ggcaaagagc ctgtcagctc agggctctct 28560
tcctcttctt ataaagtcac cagtcctatc atgggggccc caccctgatg atcttataat 28620
cctaattacc tcccaaaggc taccttcaaa tgctatcaac atatgaattt ggaaactaag 28680
tttccagcac atgaaatttg ggggatacat tcaaagtata gcaaatatta catcataacc 28740
agtaggattc atcccaggaa atgccaaatg gcttgataat caaaaattaa tgtaactcat 28800
cgtattaaca ggatgaaaaa gaaaaaccat gtgatcatct tagtagatgc agaaaagcag 28860
ttgattaaat cccacattca tttctaactt aaaaaaacaa ctggattttg acagaggtgc 28920
aaaggcaatt tggtagagaa aggacagtct tttcaataaa tggtgctggt gcaatggtta 28980
tccatatgcc caaaatgaac tttgacccat gcctcatgcc atacacaaaa attaactcaa 29040
aatagatcag agatctgaag gtaaaattta aaactataaa acttctagaa gaaaacacag 29100
gagaaaaatc tttgtgacct tggtctaggc aaagatttca tagatatgac accgagaaca 29160
caatctatga aagaaaaaaa tcaataaatt gaacttcatc aaaatgaaac ttttactgtt 29220
caaaagacag ttttaggaga atgaaaacac aagttacaca ttgggaagaa atattcgaaa 29280
agcatttgcc tgataaaggt attgtagctg gaagacagaa aaaattctca aaactcacct 29340
agaagaaaat aacccagttt taaaaatggg caagagatct gaacaaacac attgtcaaag 29400
aagatagatg aatagcaagt aagcatgtga aaaattctca atgttatcag tcatcagagc 29460
aatgcagatg aaacctacag tccccatgct aatgttctac aacttacaca gtggtggtat 29520
gataccacta catgcccatt tgaatggcca aaattagaaa ggttgaccat accaaacatt 29580
agccatgatg tgcaggaact agaactctca tctttgctga caggaaggta aaatgataca 29640
aacacattga aaaacaggtt ggcagttgct tttttttttt tttgagatgg agtcttgctc 29700
tcccaggctg gagtacagtg gcgcgatctc agctcactgc aacctctgcc tcccaatgaa 29760
ttagaaaaat aataataaag gtaacaatag cagtaataat aatagaaata atgatagttt 29820
ctttaataaa aatgctgttt aggcccagac tgaaaggctt taagtaacca ctcccccact 29880
gaagttagag ttaagaaaga atattaattt tccttgtgtg aaacattaat cttatctagc 29940
ctccatgtat tttgtaagtt ctgtaaattc ctgttttccc tgcacagctg caagttcaca 30000
aggcagataa gcttaagctg caaaacatgt ttttcttaag atgtaaggca tgtcacaaga 30060
atatcacaag atgataacgg cctttattct cacttctgta tgcctgcttc ctgcctcaca 30120
tatttcctgc ctcaagatgc gtaaaaggta cttgccttct ttgtttggtg ctctgacttt 30180
ctggatgcaa gtccactgag ccagtgtaca ccttaaataa atcctcctga accccatcaa 30240
tcgctccagt tctctgattt cccactacat tttctggggg ctcgtccggg attggagatg 30300
gcagattttc tgtctccctt gcctgtggaa ctggagcccg ggtcgaggga gacctgggac 30360
ctttggtgcc aatgggagga ctttagcccg gaaaggagat tggctctcct gcatcccggt 30420
gtccttccta gacagcacaa cggaacctat aaaggggttg caggacggtt ccagcagggg 30480
ctggggatgg tgagagtagc tcactgattc agatgacagg gttttgccat gttgcccaga 30540
cccagagggg ctggggacag tgagagtagc tcactgattc agatgaaact tacaccttag 30600
ccgatgcagg acacgagagt ggctcactaa gttggtcagg aaagaaactg aaaatgggaa 30660
gagtggcttc ctgccttgac taaggatcgg gaactgggag cggggaggtg tgtgaaagag 30720
atggttccgg gagggccgtg atgtggggag acacagatct cttagcacgg actgtgtgct 30780
ctgaggcgag tgtgtgattg accagaacca gggcatcaca tacagctgac aggagctgcc 30840
ccacagctgc agcaggctgt ggcaggaata aggtactctc ctagctaagc agcacctgaa 30900
acttccgtaa taggacccag tctggtcagt ctggaacgaa agtgagagtg agtgtgcatc 30960
acaaagggcg ggatgggagg aaaagcatcg aaacccactc ctctggggtg catgttaaag 31020
aattttaaga aaggttttgc tggagattat ggaattaagt tgtccccccc aaagattgag 31080
ggttctgtgt gaagtggaat ggccttcttt taatgtcggg tggccagccg agggtacaat 31140
aaatagggaa atgattggtc atatatttag ggtagtgact ggggttggag gacaccctgg 31200
gcatccagat cagttcccat acatcaattc ctggatgatc acagtctaga catgccccaa 31260
atggttacag ccttgtctgg caacttactg taagactcta gtgacctgag ccgaacctaa 31320
ggcagttaga gggccccctt caccagacac ctcaggtgga aagaaaaagc cacaggaaaa 31380
ttaggaaaga cctgttctac ttcactggga tcaagtgatt ctcctgcctc agcctcctga 31440
gtagctggga gtacgggtgt gcaccaccac gcctggctaa tttttttaaa ttttattttt 31500
agtagagacg gggttttgcc acattggcca ggctggtctt gaactcctga cctcagacag 31560
tctgcctgcc ttggcctccc aaagtgctgg gattacaggt gtgaaccacc atgcccagcc 31620
agcagtttct tataaagtta aaccaatgcc taccatgaga tctggcaatc ccactcctaa 31680
gtatttggcc aagaaaaaag aaagcatata ttccatacag agtctagtcc tgaatgtcta 31740
tagctgcttt atttataata gctcagactt ggaaaccatt cagatgccat taataggtga 31800
atatattctc aaactgtggt tatccataca atggagtatt actttgcaat caaaaggaat 31860
ggcctatgaa tacccataac aacatggatg aatgctgaaa taattgtgct gagtaaaaga 31920
agacaggaaa aataagtata atacatactg cttgattcta tttgtataaa actagaaagt 31980
acaaactaat ctgtaatgac aggaagcaga ccagtgacag tgggcatgga ggggcaagag 32040
ggagagatta gatgggcaca ggagagcttt gaggatgatg ggtctgcgta ctgtctcggc 32100
tatgatagtg gtttcacagg ttgatacata cggcaaaaaa taccaaattt gtacacttta 32160
aatatgtaca gattattgta tgccagttac atgtccataa agctttcttt tgttgttttg 32220
tttttatttt attttttgag acagagtctc gctccatcgt ccaggctgga gtgcaatggc 32280
accgtctcag agcactgtaa cctccgcctc ccgggttcaa gcgattctca tgcctcagcc 32340
tcccaagtag ctgagactac aggcatacgc caccatgccc agctaatttt tctattttta 32400
gtaaagacag ggtttcgcca tgattgccag gctggtcttg aactcctgac ctcaggtgat 32460
ccacccacct cggcctccca aagtgttggg attataggca tgagccacag caccgggccc 32520
ataaagctgt cttttaaatg aaaaaaagtt gtcttgaaat aagcattaga actgtggctt 32580
tggctctgaa atcctcatct gaggacccac actcgggtgc cccaatgtgg cggtgcttac 32640
agaaatgact ccatctgcta aatgagtaaa tgggtaattc tccactgaac acacactcgt 32700
ttagcagcat aagcagcaag agttcaggta atcctcacat tgcaatttgt cattagttta 32760
aacttccagt ctttgtttta aaaacacatt agaataatac tacattttcc ctcatctcta 32820
aacttgactg aagactccaa gagagagtaa tattcatcaa gaggatcatc tactcaacac 32880
agataaactg ggaaagaaaa ataacttgtg agtaattcag aatctggatt atcaggtcag 32940
gctcaatggc tcacgccagt agtcccagca ctttgcgggg cccaggaggg cagatcactt 33000
gagttcagga gtttgagacc agcctgggca acatggcgaa accctgtcta tacaaaaaat 33060
agaaaaatta gccaggcatg gtggcatgtg cctgtagtcc cagttacccg ggaggctgag 33120
gtgggaggat cacttgagcc tgggaggtcg atattgcagt gagctgtaat tgcaccatgc 33180
actccagcct gggtgaaaga aggaaactct gtgtccaaaa caaaacaaaa caaaacaaaa 33240
aaagctaaat tatcaaatgt ctagatcgtt gatggttgga agtaaagttg agaaatgttc 33300
acactgggag atgacacaca gtaaaccaca cagagggttc taacgtggtt gttagaagca 33360
gaaactagag gcttgctgcc tgaggtcaaa ccccggtccc ggtggttctg tgccccagcg 33420
catgttgtgg tagcctctct gtacttcagt ttcctcatct gtaaagtaaa cataatgata 33480
atgcctgcct catggggttg ctgttaccag gaagtgagtt aatgcacatt aggttcttat 33540
ttatgacagt gcctggcata ggataagggc tcaaaaagtg ttagctggaa ctactatcat 33600
tatcaacatc tctaatttat tgcagggttg gatctgaaaa atggctgatg atgatttgat 33660
gatgacttca tttttataaa acaataatat tgcagtgcaa attaaacaca agcaacctgc 33720
aacacgccac tgcaagttgg atgtctagaa aaggtgccat gagttacctt ctaaaacatc 33780
ataagaaacc atgttcacca ataattacca taataggaga gaagtaccaa gtaccatggg 33840
gagacagagt ccagaatctc agagagagac acagttacct tttagttaca ctaatgggga 33900
aaacaggagc tttgctaccc ttgcacctga tggagggctt ctctgaatat agggctatgg 33960
ggtcagaagc cagtttcctc ccatatttag aaggtttcca actgttatct ttcacttccc 34020
atgttgctgt tggaaaatcc aaaagtattc tatttggcca ggcacagtgg ctcacacctg 34080
taatcccagc aatttgggag gccgagatta cctgaggtcg gaagttcaag accagcctgg 34140
ccaatatggc aaaacctctt ctctacaaaa aatacaaaaa ttagccaggc gtggtggcgc 34200
acgcctgtag taccagctat tcgggaggct gaggcacgag aattgcttta acctgggagg 34260
tggaggttgc agtgagctga gattgtgtca ctgcactcca gcctacgcga cagagcaaga 34320
ctccgtctca aaaaacaaaa aaagtattct gttggatcgt ttgtgtgcga cgtgtttttc 34380
cctctcagaa agctcgtagg gtcttctctt tgtctccagc atggtctgga atttcccagt 34440
gagtgaccat ctgtgtgtgt gtattcatcc attccatgga gtccctgctg ggcccttgca 34500
atctggaaat tcatgcccat catttctgag aagttatcct gaacgtactg gttggtggtt 34560
tcctgtgctc catgttcttg cttcctgctc ttcggagctc ctgttatttg gttgagtttt 34620
gtctcctgga ctggtcctct cttacttctc ttgcttctcc catgttccat ctgttttcac 34680
tctactttct gtgagatcag gccctttatc ttccaaccct tctattaggt ttgcaattga 34740
gtttgtaatt ccctagaaaa gttcttattc tctgaatatc ccttttgata gcatactctt 34800
cctttttcat gagtgcagtg tttctgcatg gctctcatca gaacatgcta gtgtctccca 34860
tttctcataa ctttctagag tgaggaccat ttgaacttgg agtgccctca ttttaaaact 34920
ctgtggttga ccttgttccc ctcttttgct gctgcttttc accagacttt gaagaagcag 34980
aagtacattc agaacttgtc tgctctggca aaagacaata ctgttggctt aatctaaaaa 35040
ttgaagaaga aagctcaagg agagaagttt aaaaatatac cacctctggc tgggcgcggt 35100
ggctcacatc tgtaattcca gcactttggg aggctgaggc aggtggatca cctgaggtca 35160
ggagttcaag accagcctgg ccaacatggt gaaaccccgt ctctactaaa aatacaaaaa 35220
ttagccaggt atggtggcag ccgcctgtaa ttccagctac tcgggaggct gaggcaggag 35280
aatcacttga acccaggagg cagaggttgt ggtgagccaa gatcacgcca ctacactaca 35340
gcctgggtga caaagtgaga ctccgtctcc aaaaaaaaaa aaaaaaaaaa aatatatata 35400
tatatatata tatatatata tatatatata tatatatata cacacacact aaccttcagc 35460
atataggact attgcagaag ggattatctt tctacttggt tggttcctct tggtcttgag 35520
caaattttga cttccctgag ttggccccta aaagttaaag ggaaagggcc ttttctcttt 35580
cctttaaaac caatatggca tatttgctga gaacttagat accacaggat tggcagtgta 35640
gacttacatt catagaccgg atgccatcag ccaaccttga gtaatttgca gcacactgca 35700
tcattttatt taagtaatgc gaagtccttg acatgtctca gacattgtct tggttacttg 35760
taaggtctca cataaatcta attttcctct ttctctgccc tttctggttc agctcagttt 35820
attcaagggt gtatttgtgc aacacacttg aataaggtgt ggtcccgcct ttgtagatgt 35880
tatagtttgg gaagaccagc cgggcagaga gaagagcatg attcaaggat gaaggcgtgg 35940
gctgggggcc gagggagcaa ggattcccag taacgaggga ggaaggagca gcaccatgtg 36000
cccattactc tatagacatc tcgaaccacc tggccatgta gctgtcatta acctaaattt 36060
acagttattg aaactgaggt tcagccaggc gtagtggctc acgcctgaac acaggaggcg 36120
gaggttgcag tgagccgaga tcacgccact gcactccagg ctaggtgaga gagcgagact 36180
ctgtctcaaa aaaaataaat aaataaaaga aaagaacaaa actgaggttc aaagaaatgt 36240
acagtgctcc cccccttatc caaagaggat acactccaag cccccacagt ggatacctga 36300
agcctcagat agtatcaagc cctatatatg ctatgttttt tccctgtata tgcataccta 36360
tgataaagtt tataaattag gcacagtagg agactaacaa caatgataat aaaatggaac 36420
aattataaca tacactgtaa caaaagggtc tcttcctctc tctctcagaa tatcttattg 36480
tactgtactg ggggtaacta aaaccaagga aagtgaaacc atggataagg gatatctact 36540
gtataaggtg gagttttcaa ggtcatagca ctgccttccc ctgaggttgg ccttgcagcc 36600
tctctaggca ctgctgctgc tgctaagaac ccctgtgagg tgaacactgt aagcatcatc 36660
attgcttctc agaagaggag acctggctta cagaggtcaa gcctcaggta ccttaaacac 36720
cattttaaaa ctgaactcat ggccaggtgc attggctcat gcctgtaatc ccttctctcc 36780
atgctcaaaa cctgccctcc ttgtctttat attccaaatt tcgtgggtgc cacctcctct 36840
gcccagtgac ttaagccaga gcatacattc atcctagact ctgtcccagg tccctggtcc 36900
aggcagctgc cagttgtcag gatcagctct ttatctcgca gtcctcctgc ctcttgtgtc 36960
attacccagg gctgtcacca tcttttcttg ggacagttac aacagccccg taaggagttg 37020
tgctgcttct agtcttgttc cctttgaatc tggattcctt cttgccatca agacaatcct 37080
gatacaaatc tgatcacgtc acacttccct tcaatagtct tccatggctc cttattgttt 37140
taggatgaaa tccaaactcc taaacatggg gattaacaat gtgccatgat tggcactgct 37200
ggcctctcct acctctgcag actcacctct tgccacttct cccttgaggt agatcaaaaa 37260
tggtcacaag ttctttgagg ctcttcccat caagaggtag agtttatttc cccacctctt 37320
ggatctggct tgccttgtga cttgctttga cccacagaac gtaacagaaa ggacactgcc 37380
taacttacaa atgaggtcta ccttaagagg ctttgcagat tccacattca acctcttgga 37440
atgctgccac catctgagaa gcctgaggtg gcctctgtga ggatgaaaga cttcatggtg 37500
agaaatacct agcgaacagc ctggcaccag ctaccaggca tgtgactgag gccatccagc 37560
catagctgag ccacaaaatg accacagcta tgtgaattat cccaggtcag accagtagaa 37620
gagccacctg gctgagctca gcccaatttg ctgacccata gaattgtgaa caaataaaat 37680
ggttgtagtt ataagccatt aagtttcaga gtttgttaca cggtaacatg taactgatac 37740
aactcttgga gccagttgtt cagccattct caaccactta ttcaatgatg ttttgggcca 37800
tatatgcaga tatgctgttc ccttttcctt gaaatggccc ttaccctcct ttctgttggg 37860
ttttcctatg gaatatccag tcagccttta ggattcatct tgggtgtccc ttcctgtatg 37920
taggctccct ggccctccag gattccccca gtaacagccc tcatcatgct gcctttgcaa 37980
ccatttgttt atttgtacct ctcacctgct agttgggcaa gttactcact tctctcaacc 38040
tctgcatttt tcttctttat aaatgggacc aataatacct accctgccct ggcgtggata 38100
gattaaagaa aaaaaataca tgcagctgcc attgagggcc tggcccacgt gtgatgttca 38160
ataatattat ttctccttgt tttccttccc gtgccagtgc cacacccccc tgtcccagtg 38220
cactggggct gtggatccct tcaaagctga gattgcctgt ctgtggtctc cagcgttaag 38280
cacagtcatt agctcaggtg cgtactcatg tgttccacga gttcaagcct cagccctgta 38340
aagtttgcct gccgtgtatc tgatatattt ctgctaaaac ccattaggcc tttcttgctc 38400
tgaaatgtca tcgttagttg tgtgtcactt cagttttgta actggccagg ccactgcgcc 38460
caggctgctt cctcgtcatc tggctgctaa atgcttcaac cttacctgcc ttgctatgcg 38520
tcccatcctg tatcaggtca gagctcttga gtggtgaata caaatttcat ttcagttgac 38580
ttttgattct tgtggcaggc ctctcggcct actctaattt gattgcaacg gacacaaaat 38640
gtgtccaaac ttgcagcttt tcttctctta ttttgatatc accatccaca aaggtaagat 38700
attttaaagc aataactaca aactttctga aaattatgaa gaagtgctgg gttttaaatg 38760
gaagtcatat agtgtgaact ttgtgtaaag tccgtaggga gttttcttgg aaatggctgg 38820
gaacattctt tttgcacctt tgaagataaa ggtaggtgga ggagctcaca gctcttgtgc 38880
catgttgggc ttgtcactct tgtttatgtg ccaaattctt ttgattacaa aattttaagt 38940
ttaatgcttt aggtattgtt gggcaagatc tagatgtatc tagttaaatg taggtgatat 39000
gcaaactatt tatgatgtat ttgatttaaa ttcattaaga tagagtgtct ttaccaccat 39060
tatagtctgg tccttttcct tctgttttaa atgtgtttcc attggcattt tctaaactga 39120
ctttgttagc gtgttaatca tttggcactg gtaatgatta atcttttctt tctttctatt 39180
ttttttcttt tttttttttg agacagagtc ttgctctgtc accaggctgg agtgcagtgg 39240
cgcagtctca gctcactgca acctccgcct cccaggttca agtgattctc ctgcctcagc 39300
ctcccaagta gctagggact acaggcacgt gccaccacgc ccagctaatt tttgtatttt 39360
taatagagat ggggtttcac catgttggcc aggatggtct cagcctcttg acctcgtgat 39420
ccgcccacct cggcctccca aagtgctggg attacaggca tgagcgactg cgcccagccg 39480
tgttcatcta tttctgtgaa ccgatgctag gtgaaggtac agagggcttt ctagcttctg 39540
ggtttgttta ttctgaaatg ttattttaaa tcttagccca acaaattgag cgaaaagact 39600
tctagatgtt aaatatgata ttcaaaaaat ataaagacaa ggtgataaat tagaattggt 39660
gggaaagaga aaaatctgtc ttctgatggt cacctgcccc agcaacacta ctcgtttgag 39720
aagacttcca tcctttaccc tcaaagtgtt ccatgaggtt ggatcagaca tcatttagca 39780
aagaaagatg taaatagatt tctgtagggt ggcattatta agcatattaa gtggttacaa 39840
tacagtaaat tagagggagt agtacagaag cataagcagt caaaaaagtg aaagtctaac 39900
gttcgtaatt attgttctgg aggcttttgt atcacatata agttccaggc tgggtatgat 39960
ggctcacacc agtaatccca acacttagag gccaagccgc gtggatcgct tgagcccagg 40020
agttcgagac caggctgggc aacatagtga aacctatctc tacaaaaata caaaaattag 40080
ctgggggtgg tggcagcgcc tgtagtccaa accacttggg agcctgaggt gagaggatca 40140
cctgggcccg ggagatcaag gctgcggtga gccatgatct tgccattgca ctccagcctg 40200
agtgacagag agagactctg tctcaaaaat aaaaaagttt tgagtgtgaa aattcaagct 40260
caattccatt tgttggttgt cttgagtgtc tgatcacata gaatataaag atgttttgat 40320
agttgggaca gtattcagct acctgctatt taatacatta tttcagaaaa tatttacaaa 40380
gggggctggg cacagtggct catgcctgta atcccagcac tttgggaggc cgaggtgggc 40440
ggattacctg aggtcaggtg ttcaaaacca gcctggccaa acatggtgaa accacatctc 40500
tactaaatat acaaaaaatt agccgggcgt ggtggtgtgt gcctgtagtc ccagctactc 40560
aggaggctga ggcacgagaa tcgcttgaac ccgggaggcg tggggttgca gtgagccgag 40620
attgcacaac tgcactccag cctgggtgac agagtgagac tgcatctata aaaacaacaa 40680
caaaaaagaa aatatttgca aaggaccttc tgggtccaag aacctcatgt ccaatacaag 40740
ggtgcacacg tgggtgagac acggcagctg ctctccagaa gcccacagtg gaggggtttc 40800
ccttcggtct ccttttattc caagcaagtg gcaaaactac tttactctta atacaaacca 40860
cttcctttta tcacaggacg cttcccaagc tctgcaactg ttgctcctga ggaagggagt 40920
ggaactgata atctgttcct ccctattgtg ttcagtatgg tttttttttt ttttttcctt 40980
ttgctggctt tgttttcctg tccctgtgat gattaaaatt cactctgcaa attagatcac 41040
ctttcccacg cagagtccct ttgacttctg ttctagatat ccattacatt tttgtagtct 41100
tcggacacac tgtgtgtgcc gctttgccct ctgggtgaca gcaggctgtg gctgcggcga 41160
cagagctgag gtgaattctc acagaccatc actgggttac tcctggagta agtaattccc 41220
aagagctcct tctgtgcaga tcgttagaaa tagatattga ggccaggcgc ggtggctcat 41280
gcctgtaatc ccagcacttt gggaggctga ggcgggcaga tcacgaggtc aagagatcaa 41340
gaccatcctg gccaacatgg tgaaaccttg tctctactaa aaatacaaaa gtagccgggc 41400
gtggtggcgc acgcccgtag tcccagctac tcaggaggct gaggcaggag aatcacttga 41460
acccgtgaaa cggaagttgc ggtgagccga gatcacgcca ctgtactcca gcctggtgac 41520
agagtgagac tccatctcaa aaaaaagaga aagaaagaaa tagacattga acacctgcta 41580
cacagcaggg attgtgctag aagtatggat gcaaagatta ggtgaatatg ttccctagcc 41640
tcacaaagca tacagtctag taggagagac agacacgtaa aaagtttcaa cagcacagat 41700
aatcagggct acaccagaat tgggcccaag atgctgcagg aatctatagg tgaatgggtt 41760
tcatgaagga agagcttctt ctcccattta taactcattt tagcctaatc ttccaaacag 41820
tcacgcatct aagagcaggt gatgcagaaa ataccctcgt gttagttatg aattaccgtt 41880
ggaatccttc cagtgtttgc acctgccctg tgctcgggta acataaaaca gtgatataat 41940
ttgatgtcta cttcctcttg tatttgtctg tttttaagtg ttctacaatt ttcatatact 42000
ctgtttcatc gttctcaaag gaatattttg attgataaat gtttagttag taagacctaa 42060
aaactgaatc tcagtagttt gagcttatga tatacaagat gcagctctaa catttaaatt 42120
ggaagggaaa tgtcaaaaag atacctgcac tcttgtttgt tgcaacactg tttacaatag 42180
ctaagatttg gaagcaacct aagtgtccat caccagacaa atagataaag gaaatgtgat 42240
atatatacac aatggagtac tattcagcca taaaaaagaa tgagatcctg tcatttacaa 42300
caacatgggt ggaactggag atcattatgt taagtgaaat aatccaggca cagaaagaca 42360
aacttcacat gttctcactt atttgtgggc tctaaaaatc aaatcacttg aactcagaga 42420
gattagaagg atggttacca gaggctggga agggtggtga ggggttgggg gcagtgaaga 42480
tggttaacag gtacaaaaaa ctagaaagaa tgaataagac ccactaggtt ttttgttgtt 42540
ttgttgttgt tgttgttttg agacagagtc tcactctgtc acccaggctg gagtgcagtg 42600
gcatgatctc ggctcactgc aacctccacc tcctgggttc aagcgatcct cctgcctcag 42660
cctcccaaat agctgggatt atgggcacgc gccaccacac ctggctaatg tttgtatttt 42720
tagtagggac cgggtttcac caggttgaac aggctggtct caaactcctg acctcaagtg 42780
atccactcgc cttggcctcc caaatgctca gattacaggc gtgagccacc gcacctggcc 42840
actgtttgat agcataatag ggcgactata gtcaataata acttaatggt atatttttaa 42900
ataacttaaa gagtataatt ggattgttgt aactgaaagg atcaatgctt gagggcacag 42960
ctaccccatt ccccatgacg tgtttagttc acattacatg cctatgtcaa agcatctcat 43020
gtaccccata aatatataca ctgagtatat accacaaata ttttaaataa tttttaaaat 43080
aaaaaaataa attgtaaggg aaagaaaatt atgaatttag aaatgtaaaa ggtctcaggt 43140
aaggaaggaa tgagaggatc atgcagaacc tcccatcatt gctgggactg gaacagaagc 43200
cctacctttt cccaacaccc tatccacctg tccctcacct ctcagctttt gtgagactct 43260
gtctgtgcta tgaaactgaa gatctaattc agtgctgttt gcattgtctt gcctcctgga 43320
ccagaggttg cagttgttga gaaaagggat ggttggttat gccttgatcc cccccagagc 43380
atttggggca taggacacgg gaactggcca gcctggttca ctcttctcga ttagctggac 43440
agcggcatgt catgtgggta ataggaaggg gtggggactt ccccgggata ttctgctcct 43500
gatcagaagc gccagtgatg tggggggagc cccagcacca gagcatgctg ggagggcgtg 43560
cagggtgggg caggtgcccg tttggcctct gctgtctatc tgggggatgc atccaaaggc 43620
aactgttcct tatctgctct tgttgggagc aaggaagggc caatttgttc aatgatccgt 43680
atacagccag tccctctggc cagagttcaa gacagtattg cctcactcta tatagagatt 43740
gtatcttggt tagctcttca ttcatagcaa gaccaatgtt tctgtaaatt aatcctggta 43800
ttgtttaaaa gcaactaaaa atgatgaaat tgtaaaactt tgaaactccc tgaatataac 43860
gacaagcaaa ctaacattgt tttattggtc gatgctcctg gccagaagag agaatattag 43920
cagggataaa aggcataggc cacatgcatt ttccacccca gtgctgagaa cacgatgggc 43980
gaaaaaggga ggtggccaca gcccatccat cacacagtct ctgcccatct acttgctttt 44040
tccttttttt tttttttttt ttttgtgaca gagtctcgct ttgtcaccca gactggaggg 44100
cagtggtgca atctcagctc attgcaactt ctacctccca ggttcaagcg attctcctgc 44160
ctcagcctcc cgagtagctg ggattacagg cacctgccac caagcccagc taatttgttt 44220
gtatttttag tagagacggg gtttcaccat gttggccagg ctggttttga actcctgacc 44280
ttaagtgatc agcccacctc agcctcccaa agtgctggga ttacaggtgc gagccaccac 44340
gcctggcccc agctacctgt tttctttctt tttttttttt ttttttcttt ttttgagaca 44400
aagtcttgct cttgtccccc aggctggagt gcaattgcat gatctcagct cactgcaacc 44460
tccacctcct gggttcaagc gattctcttg cctcagtctc ctgagtagct gggattacag 44520
gcgcctacca ccacgcccgg ctaatttttg tatttttagt agagacgggg tttcaccctg 44580
ttggccaggc tggtttcgaa ctcctgacct taagtgatct gcccgcctca gcctcccaaa 44640
gtgctgggat tacaggtgtg agccaccatg cccggcccca gctacttgct ttctattggg 44700
atgaacctca tggttaatac agttagttag tgactgcaac ttttgaactt tttgttcata 44760
gtgaaaaata ttttaagtaa tgcttacccc attatgtttc ttgtcatttg aaaaaaaatc 44820
tcccttcaga cagaatgcag aataaaatac tacagaaaat ctgtacagag tcccagcctg 44880
acttatgcta gtaggttaca gagaaagaaa gtcttctaaa ccctatgaaa ggttaacagt 44940
tctcttattt ttccctgtgt gctatttgat gatttccctg tgaactttga tgatttattg 45000
ccagaattcc aaacataata tgtgaatttc acaaaaatgg atgaaatgta tctatttttc 45060
attggtagaa gaagccaaaa catcccttcc tcaccgcact aaaagctgtt gtttacatga 45120
agcaaacctc aaatgtgaac atatttttac gcaaatgcat ttaatgggtg aatatttgct 45180
ttgggacggt attctttact ctatctggag agtctggcgt tccgtaatca ccatgtgatg 45240
acggctgccc tgacagtggc tggtagcagc acataccccc gagcctctcc gtggtgtgcg 45300
ccgtgggcac catgtgacca ttttcagaaa ggaagacagt tctggaagct aaaggtcacc 45360
tagtcagcct cgttgggtga ttgatgactc agctgggttc agggaggtgg acccgaggca 45420
gagcctctag aaggcagcgg tgggcagggc ggttcaggca ggtggcacct gggcaaaggt 45480
gcagacgtgg aatcctgaaa gcaattctca gcgctgctgc gtttccagga ggtagaagaa 45540
cagtgacaag tgcacagtcg ggtagggaca aatgtggaag ggctgggaac agtgtgttca 45600
ggagactggg cttcaatctg gaggtctcag gaagtggttt aggatgtttc agcgagagca 45660
tgatacagac taacccagga agaaccgctg ctttgtcact tataccccta tggaaatgcc 45720
gttcgctttg ctagttgaaa tagcctacca ttgtctggga ctcacccagt tagatttgtt 45780
tggactccac aaagtattct tgaccataca atcatggtcg aggaccccct acatgagctg 45840
ccttcatggc tacagggaga gcacaccaaa gtggatgtca cacccagcac acatgccacc 45900
ggcttggccc tgcgccccgc agcctgagcc acactggctg cctgttcctg gaatgtgcca 45960
acatgtttca gtcctggagc ctttgcactt ggtgttctct tcgctggaac attctccccc 46020
aagacattta cacagcttgc cccctcattc cctgaggtta tctcctgccc cctaatcagt 46080
gaggccttcc ctggcctcac cccggacact ccacacgtgc attcatttcg ttgttcacca 46140
tctgtgtccc agttacaagg gaggctccct gagagcaggg atctgatttt tgttagttgt 46200
tgttgttgct gttttgaggt ggagtcttgc tttgtcgccc aggctggtgt gcagtggtgc 46260
gacctcagct caccgcaacc tccgcctccc atgttcaagc ggttctcctg cctcaacctc 46320
ctgagtagct gggattacag gtgcctgcca ccatgcccag ctaatttttg tatttttagt 46380
agagacagag tttcatcatg ttggtcaagc tgccctccaa ctcctgacct cgtgatctgc 46440
ccacctgggc ctcccaaagt gctgggatta caggcatgag ccactgcacc cgaccctgtt 46500
ttttgtttgg ttttggtttt ggtttggttt tggttttttt ttgagacacg gtctcactct 46560
gtcgccccgg ctagagtgtg gtggcaccat ctcggctcac tgcaacctcc acctcccagg 46620
ttcaagtgat tctcctgcct cagcctcctg agtagctggg attacaggca catgccacca 46680
cacccagcta atttttgtat ttttagtaga gatggggttt tgccatgttg gccagtctgg 46740
tctcaaactc ctgacctcaa gtgatccgcc cgcctcggcc tcccaaagtg ctgggattac 46800
aggtgtgagc cactgtgccc ggcccaggga tctgtttttg tctccgctgt gtccccagca 46860
cctcaaacat attgtacgga gctgcgacag ctgcgcagtc agtgatgact gagagattcc 46920
tggccccgtg ggctatggct ccttcaacag tttgttgttt aaaggttctt cactttctca 46980
gcgtgctgat caagagacaa gcctggagga gaggctcagt ggtgctcctg tgtagatgat 47040
gaattcaggt gtatcttgga tggtaaatga cgttgcattt aaaaccaagc aagtggccag 47100
gcgcagtggc tcacacctgt gatcaaagca ctttagaagg ccgaggcggg cggatcacct 47160
gaagtcagga gtttgagacc agcctggcca gcatggtaaa aacccgtctc tactaataat 47220
acaaaaaaac tagctgggcg tggtggcggg cacctgtaat cccaaccact cagaaggctg 47280
aggcaggaga attgcttgaa cccgggaggt ggaggttgca gtgagctgag atcgcaccac 47340
tgtactccag cctgggcgac aagagcaaga ctctatctca aaaataaaaa aaattaaaaa 47400
ttaaaattta aaattaaaac aaacagccgg acgcagtggc tcactcctgt aatcgcagca 47460
ctttgcgagg ctgaggcgag cggaatacga gctcaggaga tcgagaccac cctggctaac 47520
acagtgaaac ccgtctctac taaaaaaaaa aaaatacaaa aaattagcca ggcgtggtgg 47580
caggcgcctg tagtcccagc tactcaggag actgaggcag gagaatggtg tgaacccggg 47640
aggcggagct tgcagtgagc cgagattgtg cccctgcact ccagcctggg caacagactg 47700
agactctgtc tcaaaaaaaa aaaaaaaaga ataaataaat aaataataaa aaataaaaac 47760
aaacaagtga acgttgttat acgtcagtct taccaattgt tcctctttcc tcccagtagc 47820
ttggagctcg gcggcacaac cagcaccatc tggtcgcgat ggtggacacg gaaagcccac 47880
tctgccccct ctccccactc gaggccggcg atctagagag cccgttatct gaagagttcc 47940
tgcaagaaat gggaaacatc caagagattt cgcaatccat cggcgaggat agttctggaa 48000
gctttggctt tacggaatac cagtatttag gaagctgtcc tggctcagat ggctcggtca 48060
tcacgggtaa gtgtgccgtt tcctagaaag ttttatttag aaatgtttct tcctccaaga 48120
aaactgttct ctcttttttt tttttttttt tttgagacgg agtctcgctc tgtcgcccag 48180
gctggagtgc aatggctcga tctcggctca ctgcaggctc cacctcctgg gttcacacca 48240
ttctcctgcc tcagcctccc gagtagctgg gactacaggt gcccgccacc acgcccagct 48300
aatttttgta tttttaatag agacggggtt tcactgtgtt agccaggatg gtctccatct 48360
cctgacctca tgatctgccc gcctcggcct cctaaagtgc tgggattata ggcgtgagcc 48420
accgcgcccg gccgaaaact gttctcttta gctggaaaag aagtcacact tttttgcaaa 48480
gaaagcttca gacgtggtaa agcatgacct ccagtgcccc tgggccctgg aaggcgcgtg 48540
tcacggctca cggtgccccc tcttgtgaaa gccatgcaca catcaaacag tgcttgagat 48600
tcagtcacgg ggaacagcta aagtacacag accctaaccc cagcaagccc gcggggggca 48660
gctagacatt tttaagagga gacgtgtgca agggtctgca tagaggtact gttggtaaga 48720
gggaaggatg ggaaacaagc tgtacatgcg tcaaagggaa acagataaat tgggatgcat 48780
ttatacagtg gtatatactt catagcaatt taaaagaaca gactaggcta ggcgcggtgg 48840
ctcacgccta taatcccagc actttggaag gccgaggcaa gtggatcact tgaggtcagg 48900
agcttgagac cagcctgacc aacatggtga ggccccatct atacaaaaaa aatttaaaat 48960
taaaaaaaat tagccaggca tggtggtgca tgcatgtggt cctagctact caggatgctg 49020
agggaggagg accacttgag cccaggagct cgaggctgcc atgagctatg actgccactg 49080
cactccagcc tgggtgacag tgagaccctg tctttaaaaa aaaatttttt taagcaacat 49140
tgaatgaaaa taaacaagct taatgaatat ttttatgatc caattaatgt aaaatctttt 49200
attttttatt ttttgagaca gagttttgct cttgttgccc aggctggagt gcagtggtat 49260
gatctcagcc cactacaacg tccatcttcc gagctcaagc agttctcctg cctcagcctc 49320
cctagtagct aggattacag gcacccgtca ccatgccggg ctaatttttg tatttttagt 49380
agagatgggg tttcaccgtg ttggccaggc tggtctcaaa ctcctgacgt caggtggtcc 49440
gcctgcctca gcctcccaaa gtgcagggat cacaggcatg agccactgca cccggcccaa 49500
ttaaaatctt taacactaaa caatctagta catcactggt ggaaacagac atacacctat 49560
tgcaaagggc atctcagctt taaggactca gtcacctcct gagcaagatg gagggagaac 49620
tggggagggg tcccatgggg actgtaattc tctctaggtt gtatattttt aaaagacttc 49680
agcagtgtga taaacctggg tggtgtgtac atgggtatta cagtcatgtt gcttaatgac 49740
agggacaggt tgtgagaaat gcatccttag gtgatttcat cattgtgtga aagtcataga 49800
gtacacttaa acccagatgg tagagcctgc tgcacaccga ggctctgcgg tgcagcctgt 49860
tgctccaagg cacgcacctg tacagcgtgt tactgtactg aacggcgtag gcccctgtga 49920
cacaatggta agtatttgtg cgtctaaaca taccaaaaca tatagtagaa aaggttacag 49980
caaaaataca gtattatcat cttatgggac catgatacca cagttgaact tatggtctat 50040
tgttgaccaa aatgtcactg tgcagtgtgt gactatacag aaataagctc agagaaatta 50100
agtaacttgg ctgggcgcag tggctcacgc ctgtaatccc aacactttgg gaggctgagg 50160
caggcggatc acccgaggtc aggagttcaa gaccagtctg gccaacatgg caaaacccca 50220
tctctactaa agaatacaaa acattagctg ggagtggtgg caggtgcctg taatcccagc 50280
tactctactc aggaggctga ggcagggaga attgcttgaa cccaggaggc agaggttgca 50340
gtgagcagag atcatgccac tgtactctag cttgggcgac agggtgagac tccatctcaa 50400
aaaaaagttg gggcgtggtg gctcatgcct gtaatcccag cactttggga ggctgaggcg 50460
ggcggatcac ttgaggtcag gagttaaaga ccagcctggt caacatggtg aaaccccatc 50520
tctactgaaa atacaaaaat tagccaagca tggtggtaca cacctgtaat gcctgggcaa 50580
cagagcaaga ttccgtctca aaaaaaaaaa aaaaaaaagt aagtaacctg ccacggttca 50640
tacagccaga aagacacaga gccgggcctg gaccccgcct ctcagcttgc tctagagggc 50700
tattctctgc atgctggcat gatcgcgcct tgtaaaaggt ggcagtgttc tcagcttagt 50760
caatcaggaa ttgcaagagg caagtgagcc cctgaggact ctggggggcc tttgtgaccg 50820
agcagctttg ggagtgaccc tgacagacct ttacaggtgg tgcaagtttt gactcccttt 50880
ctcctggcgc gttaagcaga ggataagcgc tgtggaagga gtgaaggtgt agggagatca 50940
tggcccccag agcagtgggg aaggggacag ggaggctgga ggagagcaag gaaaaggctc 51000
cgtgtcaggt ggcgccttga gtggcctggg taggttgtct tgcagtgaac ccgggttaat 51060
ggccttgaca atgaccgcat tgtttcctga gcactgcagg ctgcccacac acctcacacc 51120
tcggcttgcc taagcccaga gcagccttgt gaggtcgttg ttatgtttat ttaaggaagg 51180
aggaaaggag gcaggtccca ggacatcctg acgtgctgga gatcaccagc ccagaaccca 51240
gctcttaacc ccacaatgtg ggacctttct tcacccatca cagacacacc ccatgctggt 51300
tcaccgtttt cctataatga ctatttgtgc tatttattag aaaaatcttt tccttatgga 51360
tttgaaaaga tttatcttgc ttttgttttt cttttttgcc tttctttttt aaggcaggca 51420
ggctcccgca gccccacccc cagggtgaaa aatatagttc attgtctagt aaaagagttc 51480
agagatacac ttttttcttt gggtaagata tactctagag cttgttctga aatatggaat 51540
ttgtgtgagc tgcgggagtg ggtgggtgtg tggctctagc tctggaaagt tctttcctgg 51600
cagtggccag gagggctgcc cagccccctc ctgcctcctc tggcagctta aacacaggac 51660
cccttattct gtgctctctc ctgacccctg gtcctcatgc aggagggaac cctgctcttc 51720
tagggtcctt ttctaaaagt agtgtctttt aggtcattgt caagaactat aatctaaaat 51780
gtatttttaa ctcatctgga aattctgaca gaggtaaggc ttgagaattt cctgcatact 51840
agccttgtgg tctatataat ccattaaaag ccacatttaa cccaattcca cagactgaac 51900
tgtgcttccc atctaaataa attaaaagca ggccgggcac ggtggtcacg tgtgtaatcc 51960
cagcactttg ggaggtcgag gcgggtggat cacctgaggt caggagttcg agaccaacct 52020
ggccaacatg gtggaacctc atctctacta aaaataaaaa aaattagctg ggcgtggagg 52080
cgtgcacctc ttaagcttaa ggacatattt cttatgatcc aattaatgta aaatatttta 52140
ttttttattt attttttgag acagagtttc actcttgctg cccaggctgg agtgcagtgg 52200
tgcgatcttg gcctgtaatc ccggctactc aggaggctga ggcaggacag tcgcttgaat 52260
ccaggaggcg gaggttgcag tgagccaaga tcacaccact gcactccagc ctgggcaaca 52320
gagtgagact ctgtctttaa ataaataaat aaataaatag cgagggttca gggcaggaga 52380
aaaagggttc caaatttgtt ctgaaccaat tccaaggaac tttatggcac aaagaaaaaa 52440
aaggggaact tacaaaaagt gaccacactg aagcgtcctg gtcacccatc cctggttttg 52500
accaccagcc tttaaagtgg caagcgggtg ataacccatt tcttatttcc ccctcagcat 52560
ttcctcactg ttattcatac atgtggtcat ttgtactcat ctcacaattg ttaaaacctc 52620
tttcctccct tccaggtttt actgaactgt tactgcgaag tctgagagat gaggtcattt 52680
aagattattt cttatttgta aattagatcg ttcatatttg tacctaatct gatcttttgg 52740
gtaatattcc tagttatgta gactggtctc tcagaagagc cggatattaa atgcagtact 52800
ttaaacttta cacccaggag accggatggg tgaggctggt tcactcggcc aaagtaccat 52860
tttatctctg ctttttcttc ccggctttat tgccataatt gacatacaat aaactgcatg 52920
tatttaaagt gtacaatctg ttgggtgtac acacacacgc atctgtgaaa ccatcatcac 52980
actcaaaata gtgatgtaga aattttgctc cttagttcga ctaaatctgg gttcttgtgt 53040
catgaccagg aaaaattagg cacgtggaca cgttgaaggg tgaggagagc agtattgggc 53100
gaaaaggaaa aaagaaaaaa actctcagca aagctagagg ggatcctgcc aatgagttcc 53160
cagctcacag actgattagc aggccaccac acatgagctg gaggccaggc tcctcccgct 53220
gcgcaaggtg agaacttccc gtggctccac cccattctcc caatgcccag gtgggtcccc 53280
gtcccttgcg ggcctgtcca gacaagggaa ccctgggcag gttccctcat ctacacaaaa 53340
gcacctgagg taaacacttg tggggcaggt tgcagattct ctggggacgc cccccttctc 53400
tgcctcctgc atctatcagt agtgcctctg tctgtcaccc ctaaagttta cttgtgctgt 53460
ttctaattcc tctttcccca gccccgtgcc tccctgcctc cctcccccag taaaccatga 53520
atccactttc tatcattcta ggttgcttta tatttcctag aattttatat aaatggaatc 53580
atacagcacg tactctttct aggctggctt ctttcactct gcagaatggc tgtgagactc 53640
atctgcattg cagcaagcat caatagttca ttcttcatcc atcatgtgga catagcacag 53700
tttgctgatt cacgcacctg ttgatgagca tttaggttgt ttctagctta tggctattac 53760
aaataaagct gctatgaaca ttcacgtaca agtctctgta caaccctctg ctttcatttc 53820
ttttgaataa atacctagga gtatgacggc tggaacagat ggcaggtgtt tgtgtaactt 53880
tttaagaaac tgccaaaatc ttttccagca tttcagaaaa atcttagaaa atgctatact 53940
atgttatatt cccactggca gtatatgggg gagttccagt tcctccatac cctcatcaac 54000
atgaggcatg atcagtcttt ttaattttaa ccatgtcagt aggtgtgtga tggtctctca 54060
ctgtggtgat ttttatttgc acttccctgg tgattttgag catcttttcg tatgcttatt 54120
tgccatatat cttctttggt gatatttctg ttcaaagcct ttgctcattt tttaattgag 54180
ttgcttttct actattcact attgaacact atttatatat tttgaataca aatactttat 54240
cagacatgtg atctacaaat attttcccca gtgtgtggtt tgtctttctt ttctttctac 54300
tgatagtatc ttaaaaaaaa aaaagaaaaa agattgtttt gtttgttttg ttttgttttt 54360
gagatagggt ctcaatctat tgcccaggct agagtgcagt ggtgcgatca tggcttactg 54420
cagccttgac ctcttgggct caggaaaccc tccgacctca gcctcccaag tagctgggac 54480
cacaggtgtg taccaccatg cttggctaat tttttttttt tagatacaga gactcgttat 54540
gttgccaggg gtggtcttga actcctggac tcaagcgacc ctcccacttc ggcctcccaa 54600
agtgctggga ttacaggtgt gagccatcat gcccgaccag ttcttaattt tgatgaagtc 54660
caatttatca atgtcctttt tttatggata cttcatttat ttatttattt gagagagggt 54720
ctcaccctga gcccaggctg gagttcagtg gcatgatctc agctcactgc agcctcaacc 54780
tcccaggccc aggtaatcct cctacttcag cctcccaagt agctgagact acaggtacct 54840
gccaccatgc ccgggtaagt tttttgtatt tatttgtaga gacggggttt cgccatgttg 54900
cccaggttgg tctcaaactc ctgggctcaa gtgatctgcc catctcagcc tcccaaagtg 54960
ttgggattac aggcgtgagc caccatgccc agccatatat atatatatat atatatatat 55020
atatatatat tttttttttt tttttttttt tttttttttg agacagagtc tcactctgtt 55080
gcccaggctg gagtgcagtg gtgcaatctt agctcactgc aacctccttc tctgaggttc 55140
aagtaattct catgcctcag cctctttagt agctgggatt acaggcatgt gctaccaggc 55200
ccggctaatt accagcctta tatttttgaa ctctgtttaa aacatttagg tgcataaaca 55260
ttcaggcttg ttatattctg ttgatgaact gaacctttta ttattatgaa attgctgttg 55320
taatccgtgg taaaattatt tgttctgaac actactttgt ctgttattga tgtagccact 55380
gcagctttct tttgattggt gttaacatgg tatatctttt cccattcttt ttcttttaac 55440
tggtttgtgt ctttatacta tggtttgatt taaatctatt atctcacaat ttgttctctt 55500
tggtacatct ttgttttgtt cccttttcct ctttttatgc cttctgttga attaattgag 55560
tcttttttgt tttgtttcat ttaattttgt tttttgagac ggagtctctc tctgtctcca 55620
ggctggagtg caatggcgct atctcggctc actgcaacct ctgcctcctg ggttcaagca 55680
attctcctgc ctcatcctcc tgagtagcta ggatcagagg catgcaccac cacgcccggc 55740
taatttgtgt gtgtgtgtgt gtgtgtattt ttactagaga cgggtttcac tatgttggtc 55800
aggctggtct caaactcgtg accttgtgat ctgcctgcct tggcctccca aaatgctggg 55860
attataggcg tgagccaccg cacccagcct aattgagtca tttttaagat tccactttat 55920
ctcctttgtt ggcttattat ttataacacc ttctggtgtt attttagtag ttgctttagg 55980
gtttatagtg tatctctcta atgtctccca gtctaccttc cagtggtatc attctatctt 56040
acagatatta taagaacttt atgacagtat actttcattt ttcccttcat gcatttgtgg 56100
taatgtttca cataatttta tttatttacc tacattataa atattacaat atgttattgt 56160
tttacataga cagccggtta tctttttaag atagtagtaa gaaaaatttt ttacatttac 56220
ccacataatt accttttcta gtgctatata cctttgtata aatccagatt tccatctgct 56280
atcattttcc ttctgcctga aagacttcct gtgatattat ctataatatg gctctactgg 56340
taacgaatta ctagcttttg tatgtctgaa aaagtcttca tataaccttc attctagaaa 56400
gtatgtgatt caaagggccg ggcacagtgg ttcacgcctg taatccgagc actttgggag 56460
gccgaggcgg gtggatcacc tgaggtcagg agttcaagac cagcctgacc aataaggtga 56520
aaccctgtct ttactaaaaa tacaaaaatt agctgggcat ggtggctcat gcctatagtc 56580
cctgctactt gggaggctga gacaggagaa ttgcttgaac ccaggaggca gaggttgcag 56640
tgagccaaga tcacgccact gcacaccagc ctgggtgaca gagcaagact ccatccccct 56700
gcaaaaaaaa agaaaaagaa aaagaaaaaa gtatgtgatt ctacattggc aatttttttt 56760
tttttttttt ttttgagaca gagtctcgct ctatcaccca ggctggaggg cggtggtgcc 56820
atcttggctc actgcacgct ccgcctccca ggttcacacc attctcctgc cccagcctcc 56880
caagtagctg agattacagg cacccaccac cacacccggc taattttttt gtatttttta 56940
gtagagatgg ggtttcacca tgttagccag gatggtctca atctcctgac ctcatgatcc 57000
gcccacctcg gcctcccaaa gtgctgggat tacaggcatg agccaccgag cctggccact 57060
ttttttcttt aaatgctttt aagatgttcc tactatcttc ttgtttttaa ttaattaatt 57120
tattattatt attattatta ttattattat tatttttttt tttttttttt tttttagaga 57180
cagggtcttg cgctgatgcc gaggctggag tgtgctagtg ccatcgtagc tcactgcagt 57240
ctcaaacacc tggtctcaag caatcgtcct gcctcagcct cctgaggaac taggactaga 57300
ggtatatact accatgccca gccaatttta aaaatttttt gtagaggtgg agactcgcta 57360
tgttgaccag gctcctctcg aactcctggc ctcaagcaat cctcctacct ctgcctcccg 57420
aagtgttggg attacaggga ttacaagtgt gagccactgt gccagtcccc actgtcttct 57480
ggcttgcatc gtttctaaaa gaaacttggt gtcatcctta tttttgtttc tctacatgtt 57540
atatgtcctc tttatctggt tgctttaact ttatttatta attttagttt aatttttaat 57600
tgacaaataa taattgtatt tttatggggc acaatgtgat gttttggtct atgtttacat 57660
tgtggaatgt gtaaatcaag ctagtgaaca tatccaccac ctcacacact taccattttt 57720
tgtgtgtggt gagaacatgt aaaggctgct ccttgaggcc aggcccaatc ccagcacttt 57780
gggaggccga ggcgagtgga tcacttgagg tcaggagttc aagactagcc tggccaacat 57840
ggtgaaaccc cgtccctact aaaaacacaa aaatcagcca ggcgcggtgg tacacgccta 57900
tagtcctagc tacttgggag gctgaggcag gagaatcact tgaacccaag aggcagaggc 57960
tgcagtgagc caagatcatg ctactgcact ccagcctggg caacagagca agactccatc 58020
tcaaaaaaaa aaaaaaaaag tctattcctt gagcaatttt gaaatacaca atacatcatt 58080
gttaattatg gtcaccatag tgggtagtag atcactaaat cttattcttc ctgtctaact 58140
aaaacttttt tccttttgac caacatctcc ccattccctc cctcaacctc agcccctgat 58200
aaccaccatt ccactctcta ctgctatgag tttgaccttt ttagatttca catatgagat 58260
cacatggtat ttgtctttct gtgcctggct tcttttactt agcataatac cttccagatt 58320
tacccatgtt gttgcaaatg gaatttcctt cttttttaag gctgaatagt attcgtgtgt 58380
gtgtgtgtgt gcgtgtgtgt gtgtgtgtgt atcacatttt ctttatctct tcgttcatta 58440
atgatcattt aggatgattc cacatcaggc tactgtgtat agtgctgcag taaacatgga 58500
agtgtagaca tctcttcagc atactgcttc caatctcttt ggatataaac ccagaagtgg 58560
gattgctgga tcatatgtag tgctattttt gtttttttga ggaacctcca tacttatttt 58620
gcataatgct attctaattc acaatactac caacagtgga catgggttct tttttctcta 58680
catgcttgcc aaccacttgt tatcttttat ctttttatat atctggctgc ttctaaattt 58740
ttttctttct taccaattct gaaccatttg atggtttctt cctttatgct ccttgtgctt 58800
gaggttcatt gagcatctgg gatcagtgca cttattgttt tcatcaaatt cagaagatta 58860
ggccattatt tcttcaaact tttttgtcgt tctctgtcta cctttgagag ctccaattat 58920
acatacatta ggccacttga agttgtcatt acagttcact aatgctaagt tcttttttta 58980
agtcttgttt ctgtgtttca ttttggacac tttctattgc tacatcttca aatttactaa 59040
ttttttcttc tgcaatatct aatctgctcc taatcctatc cagtgtattt tccatattag 59100
atattgtagt tttcataact agaagcatga tttggttctg ttttcaccca tgtatctata 59160
taacatgtcc agtctttcac tcagcttctt aaacatttag aatatggtca gaataacttt 59220
ttttgctgtt ttgttttaga gacagggtct cactttgtta ctcaggctgg agcgcagtgg 59280
catgatcaca gctcactgca gccccaacct cctcgtctca aggaatcctc ccacctcagc 59340
ctcctatgta gctgggacca caggtacaca ccaccacacc tggctaattt ttaaattttt 59400
tgaagagacg ggtctcactt tgttgcccag actggtctca aactcctggg ttcaaacaat 59460
cctccagcct tggcctccca acgtgttggg attacaggca tgagccactg tacccagccc 59520
agaataactt tttaaaaatg tcttgaggcc gaggttggga aataatctga ggtcgggagt 59580
tcgagaccag cctgaccaac atggagaaac cccgtctcta caaaaaatac aaaattagcc 59640
aggcacagtg gcacatgcct gtaatcccag ctacttggga ggctgaggca ggagaattgc 59700
ttgaacccgg gaggcagagg ttgtggtgag ccgagatcac accattggac tccagcctgg 59760
gcaacaagag cgaaactcca tctcaaaaaa aaaaaaaaaa aaaactctta gccacaattt 59820
ctatcatctg tgtcacttct gagtcccttt ctattcagtt atttttctcc ttgtcatggg 59880
tcatattttt ctgattcttc atgtgtcctg taattttctt ttcttttttt ttttggagat 59940
ggagtcttac tctctcaccc aggctgtagt gcgatggcac aatcttggct cactgcaacc 60000
tccacctcct gggttcaagt gattctcctg cctcagcctc ccaggtagct gggattacag 60060
gtgctcacca ccatgcccag ataatttttt gtatttttag cagagacggg gtttcaccat 60120
gatggccaag ctggttttga actcttgacc tcaagtgatc cgcccacctc ggcctcccaa 60180
agtgctagga ttacaggcat gagccaccgt gcctggccag ttgttctcat tggatgtcat 60240
atgttgggaa ctttattggg tgatggatat ttttgatttc ctataaatat tcttgaactt 60300
tgttctggga tgcaattaag ttacttggaa aatctttgat cctttcaggt cctgtttctc 60360
agcttcatta gatgggacta tcacagtgtt tgttttagag ataactttgc cccactgctg 60420
aggcaaaacc actttgagct tcacctgatg ccccatgact tcagtgatct tccactgtgg 60480
gaggcgagag caggactata tccagctcca tgtgggcccc aggcagcgtt cactatcatc 60540
atttcaggtt gctactgaag tatccctttt tcaggctctc agctggcaga gcaaatacat 60600
atatgtatac atactaacct atgtctatac aggaatctat cggtatttct gtctgtggcc 60660
atctgtagct gtatgaagcc aaacatgagt gtgtgctgat gtctccagcc ctcatctgtt 60720
accagatgga tcgttctagc ctcctccact tgcctacctg tcaattcacc attccttgag 60780
ttcatggttc attttcagta tacctgcaca gtggtatcag aactgttaac ccacaccctg 60840
tgggaaaaaa actccatcag ctagagcaca gtgtttacag ccagatcctt ttgcctttag 60900
tcttacagat tccaatcatt ccaaattatt cggtgcagcg cctttccgca cctgcaccca 60960
ctttttcccc tgagattgtt tcctacattc gtagcacagt tagattgttt tgttacattc 61020
tgcatttcac cctgggatcc tccaacctcc taagttattt ttgttttatt tgcacacatt 61080
aggttcaatc tgaactataa agttctgtgg gttttcacaa atgcgtagtg tcatgtatcc 61140
accactacat tttccttctc tctctttctt gctttctcgc cttcttgtct tgctctgtca 61200
cccaggctgg agtgcagtgg cacaatctcg gctcactaca acctccgtct cctgggttca 61260
agccattctg ctgcctcagc ttcccgagta gctgggacta caggcacgca ccaccacccc 61320
tggctaactt tttgtatttt tacaaaatac aaaagacgat gtttcactat gtgggccagg 61380
ctggtctcga actcctgacc ttgtgatcca cctacctcgg cctcccaaag tgttgggatt 61440
acaggcgtga gccaccacac ccggtctctc tccttccttt cctttcctct cctttccttt 61500
tctttctttc tctttccctc tcctctcttc tcctctcctc tcctttgatg gaggtctcac 61560
tgtgacaccc aggctggagt acagtggcag cataatctca gctcactgta gcctcagcct 61620
cccagggctc aggtgatcct cccacctcag cctcccaagt agctgggatt acaggtgcac 61680
accgctgagc ccagcaaatt tttgtatttt ttgtaaagat agggtttcac catgttgccc 61740
aggctggtct caaactcctg agctcaagtt atctgccagc ctcggcctcc caaagtgctg 61800
ggatgacagg catgagctac cgtgcccaga ccactgttag attttcatat gaatagtttc 61860
accacatcaa aaaaccccat gcttcaccta ttcaaccctg cctctcccac ccccagccag 61920
ctcagaaatg gttcttttta ccattgctat aattttgcct tttccagaac gccatgaatt 61980
tgaaatcata tagtatgtag ccttttcaga ctgacttctt tcatagcaat atgcatttaa 62040
gagtcatcca tgtctttcca tggcttgata tctcatttct ttttacactg aatgagttcc 62100
cactgtctgt ttgtaccaca gtttgtatat ctattcacct atctaagggc atcttggttg 62160
cttccaattt ttggcaatta ataaagctgg ccatgcacag tggctcacac ctgtaatccc 62220
agcattttgg gaggccaagg cgggcagatc acttgaggtc aggagtttga gaccagcctg 62280
gccaacatgg tgaaacgctg tctctactaa aaatacaaaa attagccggg cgtggtaatg 62340
ggcacctgta atcccagcta cttggaaggc tgaggcagga gaatcacttg aacctggagg 62400
cagaggttgc agtgagctga gatcgtgcca ctccactcca gcctgggtga cagagtgaga 62460
ctctgtccca aaaagaaaaa gaataaactg ctgtatacat gtgtaggttt tgtgtggaca 62520
gaagttttca aatcagttgg acaaatacct aagagtgtga ttccatcata cagtaaaact 62580
gctttgcttt gtcagaaact gccagaatgt cctccaaggg ggctgtctca tgttgcattc 62640
ccaccagcaa tgaatggggg ttcctgttgc tccacatcct caccagattt gatgatgtca 62700
gttttgtgga ttttagtcat cctagtaggt gtgtggtgac accacattgt tgttctcatt 62760
ctcagtgccc cgatgacata tcatgctgag cattgtttca tatgcttact tgccatctgt 62820
atatcgtcct tgctgaagtg actgttcaga tgttcagatc ttttgcccat tttctttctt 62880
tttttttttt tttttccttt tgatacggag tcttgctctg tcgccaggct ggagtgcagt 62940
ggcacaatct cagctcacta caacctttgc ctcccgggtc caagcgattc ccctgcctca 63000
gcctcccaag tagctgggac tacaggcacg caccaccatg gcaagctaac tttttctttt 63060
ttttttcttt tctttttttt ttgagatgaa gtctcgctct gtcacccagg ctggagtgca 63120
ttggtgcgat cttggctcac tgcaagctcc gcctcctggg ttcacgccat tctcctgcct 63180
cagcctcccg agtagctggg actacaggcg cccccaccac gcccggctaa tttttttgtg 63240
tttttagtag agacggagtt tcaccgtgtt agccaggatg gtcttgatgt cctgacctcg 63300
tgatccgctt gctccggcct cccaaagtgc tgggattaca ggcgtgagcc accacgccta 63360
gcccccattt ttcaattgag ttgtttgttt taagacctct ttgtatatta ccacatgtgt 63420
attgaaaata ttttctccca gtctgtggct tgtctttaat tttcttagca atgtcttttg 63480
cagagcagaa ggtttcatta gctttcatag attccaactt atattttctc tttcatggat 63540
tgtgcatttg gtgttgccca cacagatttt tatactgtat tctggtgcca tttactgagt 63600
taacaattgc ggaagaactg gaagaaagga agcaaacaaa acgagttctg cgtggcactg 63660
tcagtgcggg ggcatgggga gtcctgcagg gtgaggtatg ggcggtatgg caaggcgcgg 63720
gcccatagat gtgcaggtct ggagatgtgt gcagcggaga tgtgcgggcc cgagatgtgc 63780
gggtccgatg tgtgggtccg gagatgtgcg cgtacccaga ggtgcagatc ggaaatgtgg 63840
gggtccggag gaaatgtgcg gatcaggaga agtgccagtc ccgagatgtg cggatcggag 63900
atgtggaggg ctaggagatg cgtgggtccg gagatgcgca gatcaggaga tgggcgaatc 63960
ggagatgcgc gggtccggaa atgtgcagag cggagatgtg tggatcagga gatgttgggg 64020
ggtcaggaga tgcgggggtc cagagatgtg ggggtccgga gatgtgcggg tctggagatg 64080
tgcagagcag agcaaagatg agctgatcgg agatgcccag gtccggggat ccacgggtcc 64140
ggagacgcgc gggtccggag atgcgtgggt ccagagatgt gcgggtccaa agatgtgcaa 64200
atctgaagat gtgtggatgg gagatgtgca ggtccggaga tgcgcggggc ggagatgtgt 64260
ggatcggaga tgctcagatc gaagatgtgg gaatgaggag atgtgcgggg cgggatgtgt 64320
ggatgggaga cgcgcgggcc cggagatatg cggggcggag atgtgcgggt ccagggatgt 64380
gtgatctgag gtgtgtgggt ccggagctcg gggtcagctc agcagcagtg agagcgagca 64440
tgctggcttt gggagcacag cacaatggca gctgtaggag tgcaagaggg tgtgacccag 64500
aggcagggcc cggccccgca tgggtgttct gaggtttatg cctcagcact agaagcctcg 64560
tatgcgaaat cacatcctca tagacccggt tcagacacag gatagtgatg cctggactat 64620
tcatccgtct ctcctctttt tccccagaca cgctttcacc agcttcgagc ccctcctcgg 64680
tgacttatcc tgtggtcccc ggcagcgtgg acgagtctcc cagtggagca ttgaacatcg 64740
aatgtagaat ctgcggggac aaggcctcag gctatcatta cggagtccac gcgtgtgaag 64800
gctgcaaggt agaggggagc tggaacaggg cctggtggcc gccaccatca actacttatg 64860
gtcactttta tagcaaatgg cagtcattac tgagagattg cagaaagtcc cggataagaa 64920
actgacttca ggccaggcgc ggtatctcat gcctataatt ccagcacttt gggagaccga 64980
gatgggtgga tcacctgaga tcaggagttc gataccagcc tggccaacat gatgaaaccc 65040
tgtctctact aaaaatacca aaaaaaatta gccaggcgtg gtggtgggcg cctgtaagcc 65100
cagctactcg agaggcaaag acaggagaat tgcttgaacc caggagccag aggttgcagt 65160
gagccaagat tgcgccactg cactccagcc tgggcaacaa gagtgagact ccatcttaaa 65220
aaaaaagaaa gaaaaaaaga aaaagaaaaa gaaactgacc tcagtgatag attagcctct 65280
ctttatagca cagaacccct gagagcgtaa gccctgttgt gaactgcgta tttgaggaat 65340
ctagcttgta cgccccttat gagaatctaa tacttgatgt tccaaggtgg aacactttca 65400
tcctgaaact atccctcccc acccccatct gtggaaaaat tgtcttccat gaaaccggtc 65460
cctggtggca aaaaggttgg ggattgctgc tttagagagt ctaggacaaa tggttcctct 65520
gtgctttgta aatacttaga gaagtgcatt ctttaaaaga aaataagtca cattggaccg 65580
ggtgcagtgg ctcacgccta taatctcagc actttgggag gccgaggcgg ctggatcacc 65640
tgaggtcagg agttcaagac cagcctggcc aacatggtga aaccctgtct ctactaaaaa 65700
tacaaaaatt agccaggtgt ggtggtgggt gcctgtaatc ccagctactt gggaggctga 65760
agcaggagaa ttgcttgaac tcaggaggcg gaggttgcag tgagctgaga tcgagccatt 65820
tcactccagc ctaggcgaca agagtaaaac ttcatctcaa aaaaaaaaaa aagagagaaa 65880
agaaaataag ccacattaag aacatcactt cattcgaata caagacagag agctgttacc 65940
gttgatctct ggagcctccc tgaaggccag gtggggcagg tgttctcatg ctcctgccag 66000
ggaaattggc catcagagac acagagtatc ttgcttaggg tcccacagcc cccagcagca 66060
gggactggaa ccagagactg gctgctcctg ctccccagca gttccttcct gcacatcagg 66120
ggcttctcca cctgattcaa gcgacaggaa ccccctgtgc atcttcatcc tcctgctggc 66180
tcagcctgcc ctaaacagat gtgacctggg ccaggagtgc atgaaggcag gccctgttgt 66240
cctgcatgct gccagctgga ctggtggccc ttccgtgttt gtcagcgtgg tgatgaggag 66300
agctcctgta gcagcgtccc tttagggttg cacagacgtg ctcaagtctg gcgccttatg 66360
tacgtgatat gtgggagatc atcatctgaa tgtttggttt gaatcagaaa tcccttctca 66420
cggtgcacgc tgcaggtgtt cactaacttg gaaaatgcca ccgcctttct ggcacaatgt 66480
accatcttgg aacaccagca ttctgccctg agccaggcct ggcctcagag gcctgggcca 66540
cagggagaac ctcacagcca ggacactgtg gcactctgct gtctagaagc ctgtctcccc 66600
acccttccca ttctaacccc atgcgttcct cagcctcccc actgtgcaag cctaggtaag 66660
gacattatga agacgtcagc ctgcctctca cattcccctg cacactgctg tccctctccc 66720
gcgggccaag cagacccact gtggcaaaaa tatagaagaa tgacttaaaa gcaaagagaa 66780
aaaagaaccc aaagcaaaaa tgaactcctt cgcatgtttt ctaaccatat acctttgaaa 66840
aagctcctta taaagtggcc ttttccttag ggccatgatt aattattcat ttagttttgt 66900
tttttatgga ctatttagta acattgtttc ttgctgggta gagtttaaga tgcttttaca 66960
aagcaagaaa attgtttaca aacagctggc ttccttttat tataattttt gtctttgagg 67020
gagttaatat actcttacaa aaattcttag aaagtcttta gtcacaaata tggaaatgtc 67080
acaatgctgg ggatagttac attcatatac attgtaacaa ggctgagtaa ctctttggaa 67140
aactataatt gtgttttccc aagtcagatg agggcatttt gaaatgactt cgaatgctgc 67200
ctcattttat tgtttttcac attaaatgta acgacattta aagttctgta tttgtcctaa 67260
tcattccaga cttcttagaa gaactatttc tttctttttt tttttttttt tttttttttt 67320
tttgagatgg agtctcactc tgtcgcgcag gctggagtgc agtggcacaa tctcagctca 67380
ctgcaacctc cgcctcctgg gttcaagtga ttgtcctacc tcagcctcct gagtagctgg 67440
gactacagac ttacatcacc atgcccggct aatttttgta tttttagtag agacagggtt 67500
gcaccatgtt ggctaggctg gtctcgaact cctgacctca ggtgatccac ccgcctcagc 67560
ctcctaaagt gctgggatta caggcatgat caccatgcct ggcctggaat aacttttctc 67620
taaattttgt tcatttaaaa agaaacaata aatgagcaac aaaaaaggtg agtaaagcaa 67680
gtgcgctggt ttctcagtgg cccaggtctt taaatccact gtgtattacc ctcacagggc 67740
ttctttcggc gaacgattcg actcaagctg gtgtatgaca agtgcgaccg cagctgcaag 67800
atccagaaaa agaacagaaa caaatgccag tattgtcgat ttcacaagtg cctttctgtc 67860
gggatgtcac acaacggtag gtaaggtggc cctgcacatt ttcccagttc gttcctcagt 67920
tccccttcct tgctccaagg gaacagatca agctatggat gaatgtgctt caacatttca 67980
cacccaagtc attttgtaat cagagtggcc taagaaaata aaagtcgccc aggcgcggtg 68040
gttcacgcct gtaatcccag cactttggga ggctgaggtg ggtggatcac ctcaggtcag 68100
gagtttgaga ccagcctggc caatatggtg aaaccccgtc tctactaaga atgcaaaaat 68160
tagctgggtg tggtggcaca tgcctgtagt cccagctact cgggaggctg aggcagaaga 68220
atcgcttgaa cccgggaggc ggaggttgca gtgagctgag attgcgccac tgcactccag 68280
cctgggcgac agagggagat tccgtctcac aaaaaaaaaa aaaagaaaaa gaaagaaaga 68340
aagaaaataa aagtctccca ggtgcggtgg ttcacacctg taatcccagc actttggagg 68400
ccgaggcggg tggatcactt gaggtcagga gtttgagacc agcctggcga acatggcaaa 68460
accccgtctc taataaaaat acaaaaatta gctgggcatg gtagtgcaca cctgtaatcc 68520
cagctacttg ggaggatgag acaggagaat agcttgaacc cgggaggcgg aggttgcagt 68580
gagctgagat cgcaccactg cactccagcc tgggcgacag agtgcgactc cgtctcaaaa 68640
aaaaagaaaa aaaaagaaaa agtctcaaat agctgagatt cagtggtgca ttggactcgc 68700
tgttagaaac ttcagtggta agactttgat acagaatcga aaaaccaagt ggaaggcacc 68760
aaaatgacag aatgttcacc tcgtccatag gaagggtgta ccacctcaaa catctcacca 68820
cgttatgaat ttccttctag ccaatcattt aatagtttca gaacatgcta attgtgatgt 68880
gaatgtaagt cgttcataag agttgcatgt ctaccttctg gaaaaagaag cagttattat 68940
ataaactcat cccgaagccc cgttcacctc cttcactcaa aggttgatga tgcacctgat 69000
agtggtgtgc accctactaa tgagacgaac gatggtgtca ccttcagcct gcacctgtta 69060
acgatggtgt caccttcagc ctgcacctgt ttaaacatct acagtgtatg gagtttgagt 69120
ttttcatctc tccatagtgg aaagccgaat agtaatgaag gatgggtctg aactgcctgt 69180
gaattttcat tcctggttta aagtcctggg ggagcccctc gtccagccct gtccgcgcag 69240
tcatgacctc actgctcatg cctgtgtttc cccctccaaa ccctagcgat tcgttttgga 69300
cgaatgccaa gatctgagaa agcaaaactg aaagcagaaa ttcttacctg tgaacatgac 69360
atagaagatt ctgaaactgc agatctcaaa tctctggcca agagaatcta cgaggcctac 69420
ttgaagaact tcaacatgaa caaggtcaaa gcccgggtca tcctctcagg aaaggccagt 69480
aacaatccag taggtgtttg cggctgttct gggttctctt ggcaacatgg aaccagtgtc 69540
gtagaggacg attaaggaca catgtgttga atgttgagaa aattatattt atcccacagt 69600
taagcaaagg acagcgaaga tggaaacagt tcattctgag actctgagct gtagcttaac 69660
aacaactcct ttcttcttgc ttggagccac ctcaaagctc ttagcaacta agttattata 69720
ctggctatgt aattaataca cttaaaaaaa accttaatag cttaccaagt actaagatga 69780
tttcttagga gcattttttc ttaaatagag ataggttctt gctctgttgc ccaggctgga 69840
atgcagtggt gcaatcatag ttcactgcag ccttgaactc ctgggctcaa gcaatcctcc 69900
tgcctcagcc tcccaaggag ctgggactac aggtgtgcac caccacacct ggctatgttt 69960
gatgttgttg ttgttttgtt ttgtttttgt tttttggtag agatgagatg tttcccaggc 70020
tggtctcaaa ctcctggcct caagtgatct tcccacctcg gcctcccaaa gcactggcat 70080
tacaggtgtg agtcatggca cccagcatta actggattta aaaaaaaaaa aactgaccag 70140
gcaagatggg tcatgcctgt aatcctggca ctctggggag gccaaggtgg gcagattgct 70200
tgagtccagg agtttgatac cagcctggcc aacatggaga aaccccaact ctactaaaga 70260
tacaaaaatt agctgagcag ggtggcacac acctgtaatt ccagctactt gggtggctta 70320
ggcatgagaa ttgcttcaac ccgggaggca gaggttacag caagctgaga tcatgccact 70380
gcactccagc ctgggtgaca gatcgagacc ctatctcaaa aaaaaaatag aataataaaa 70440
taaatcccta ctttgaggtg tattagtctg ctataaagaa atccctgaga cctggtaatt 70500
tataaagaaa agaggtttaa ttggctcgtg gcccacaagg ctgtacagga agcttctgct 70560
tctggggagg cctcagggaa tttgactcat agcagaaggt gaagtgggag taggcgtctt 70620
gcatggcagg agcaaaaaca agagacacac acttttcacc catcagatct tgtgagaacg 70680
ctatcactag agtagcacca agaggatggt gctaaaccat tcatgaagga tcacccccat 70740
gatccagtcc ctcccgccag gcctcacctc caccactggg gattacagtt caccatgaga 70800
tttgggtggg gacacagagc caaaccatat cataaggcta gaaaaggaaa ccacttactt 70860
cccactcaaa atgtgctctt ggtcctttct cctaaaacta ctccctccct ctcagacaaa 70920
catgcctaca ttctttttcc gccttcagtg aaaagacagt gacatcttgg ggcttagaaa 70980
gggccacttg taagccaggc gtggtggctc acgcctgtca tcccagcact ttgggaggcc 71040
aagacaggcg gatcacgagg tcaggagatc aagaccatcc tggctaacat ggtgaaacac 71100
catctccact aaaaatacaa aaaattagcc gggcgtggtg gcgggcgcct gtagtctcag 71160
ctacttggga agctgaggca ggagaatggc gtgaacccag gaggcagagc ttgcagtgag 71220
ccgagatcgt gccactgcac ttccagcctg ggcgacaaag ccagctgtgt ctgggcgcgg 71280
tggctcatgt ctgtaatccc agcactttgg gaggctgagg tgggtggatc acttgaggtc 71340
aggagtttga gaccaccctg gccaacatgg tgaaacccca tctctattaa aaatacaaaa 71400
aattagctgg gcatggtagc ggttgcctgt aatcccagct acttgggagg ctgaggcagg 71460
agaattgctt gaacctggga gctggaggtt gcagtgagct gagatcgcac cactgcactc 71520
cagcttgggc aacagagtga gactctgtct caaaaaaaaa aagaaaggaa aagaaaggac 71580
cacttgttat agaaagcctg tcttttaagg tagctctgga ccttttcaga ggcagccaaa 71640
ttgcccctca tggttcgtcc cccacatccc cgcctgcctg gcctaagtcc tccttccccc 71700
tccccaacag ttaaataagt ctttgtctcc attacaaaac aaatctcaga gctaccttca 71760
aagaagagcc agccctcagt tggtgaatga agatactttg acattttcct atgagcatgg 71820
tgaaacaggt ttaatttgta ttaaatagct tgaagcaatc cttattggga attacaaggt 71880
ggaattttag tcacaggaaa ataaagcatt tcacaagcta cttactttca tgaacaaacc 71940
aaacctcttc tttactgagt cctttaattc ttcagtgaat tctccaatta aataggccga 72000
gacattttag aagtttccag cagacaccca cactaggcag ctccagaggc ttgtcccaat 72060
tagaactttc ctggattacg agagtgaaag aaaaggtaac ttttagcttc gagtctctat 72120
cctggatatg attagtacag cccaaaattg ggatggctaa aacttttgtt tgccagctta 72180
tatttctccc ttggatttca gaattgaaag caggctgggc acagtggctc acactgtaat 72240
cccagcactt tgggaggctg aggcgggagg atcacttgag gcaatccaag agtttgagac 72300
caggcaacac aaggagacct cgtctctaca aaaaatgatt ttttaaaaaa ctagctgggc 72360
atggtggcat gtgcctgtgg tcccaggtac ttgggaagct gagatgggag gatggcttga 72420
gcccaggagt tcaaaaccaa cctgggcaac atggcaagac cacatctcta caaaaaataa 72480
aaacattatc caggcatggt ggcacatgcc tatagtcccc gcgacttggg aggttgagga 72540
ggatgccttg aggccaggag ttcaaggctg cagcgagcca cgatcgcgcc actgcactcc 72600
agcctaggcg acaaagcgag actctctaaa aaaaattcga agcagagtta agttgtcttt 72660
cttcctaaca acctgccccc accatggggt gcgaatggga ctcctggagt cctcctgcac 72720
ctccccttgg agaccaccaa gctctaggaa ccccatcacc ctcagctgag ggtcacatgc 72780
agcaactagc aggcgggaat ctgtttgcat tttggcctta aagaaataaa taataggcca 72840
ggcgcggtgg ctcatgcctg taatcccagc actttgggag gctgaggcag gtggatcacc 72900
tgaggtcagg agttggagac cagcctgacc aatatggtga aaccccgtct ctactaaaaa 72960
tacaaaaatt agctaggcat ggtcgtgggc acctgtaatc ccaactaccc aggaggctga 73020
ggcaggagaa ttgcttgaac ctggaaggca gaggttgcag tgagccgaga tcacaccact 73080
gcactccagc ctgggtgaca gagcgagact ccatctcaaa aaaaaaaaaa aaagagggcc 73140
aggcgtggtt gctcatgctt atgcctgtaa tcccagcact gtgggaggca gaggagggcg 73200
gattacctga gctcaggagt tcgagaccag cctgggcaac atggtaaaac cccatctcta 73260
ctaaaataca aaaaattagc cgggcatggc agtgtgcgcc tgtagtccca tctattcggg 73320
aggctgaggc aggagaatgg cgtgaacctg ggaggtggag gttgcaggga gccgagatca 73380
caccggtgca ctccagcctg ggtgacagag tgagactcca tctcaaaaaa aaaaaaaaag 73440
aaagaaatga tagatgaata gtttaggatt ggggttcaca atttggtttt ctgtagaaaa 73500
agagaaccgg gcactcttcc gagagtcaga tgccctcttc cacccacacc cacaaagcca 73560
gagcaccgca ggtaccagtt ttcaaggcaa cctccaacca tcatgtgact ctttgtgttt 73620
gatcacactg tttgctccaa gccagggttg cgtcccaccc catgtccttg tctgcgcacg 73680
ggacgctgga ggcacggccc cctcctccct gcctagcctg ctgacgggct ttccagagct 73740
ggctccttca ggtgcaggat accctctctg cttagtctgg gaaaaggccc cgttggcagg 73800
atgcccacca ccaggccaca ctgcctgaat ctattggcag agctctggtt ttgtggccaa 73860
ggtgggtagt ggaagaccat agcctgtgtc ccttacacat ctcagaaagc aaccccatct 73920
gtgggcaaga aatctgttag ggagaccaag cagcggcctg gaaacacctt gatctctgcc 73980
cagtggccca catgcggtcg ccgtttcatc agtttccagc ctgggtgacc tcacagcccc 74040
agccacgccc cacagagcct caggaaggca cactgacctc agggccggcg gctgacttca 74100
tttctgtttg gggatgagag gcggcacagt aaactgtcca ggccagtaaa ctaatggatt 74160
catacgaacc gtaatgaacg tgggctgtgt gctggggaag gcaggctcgc ctcctccctg 74220
caggggctgc tggggtgaaa gcaaccctga aatgttcaaa gccttgatgg ggaagcacgg 74280
gggatggata gattttaatt tcaaagcagc cctctggttt gctataagcg ggggactgaa 74340
tttctctttg cagtggccaa tgcctttctt ctgtcaagat cagctcgtgg ccttcagatc 74400
agatgacgca aagccccatg gctgagctgg aacaggctag aatgctgggg gggggcctga 74460
aaccggtggg ggagttgtgg gaggcctaga atcagccagg aggcttgggt cggggttgga 74520
accggccagg gtgcacggag gaggctgtgg gggcaggggg aggccgctgc atggagccgc 74580
atagatgcca ttgcttgagg aaaggtgggc tttagctgag ggaaggagtg aggggtggat 74640
ggagaatgtc tgtgtccatc tggacactgg gactgtttga gcccctgaga tttcagaacc 74700
gtgggccaga aaatggtcag ggcccttggt gatggggaag ggcgcctctg gggaactcac 74760
tgccccttga tttgagggta acagggatgg aagcagagtc agggggctga gggaggcaat 74820
aaaaatgggt gcttttcaac agtgtctaaa aacataagat gttgacctgt caggggttga 74880
gaatgtcgtc agaagacttt ggaggaagca acagaaaatg agactgaggg gcttgggcag 74940
agtcagtgcc ttctgtgtga tgcacgctca tgcacaaatg cacgcacata cccacactca 75000
cacatccgtg cacacacggg tacacacaca tacacgtgca cccacatgca tgctcacaca 75060
catgcaccca cagtcacaca tccatgcatg catgtgtaca caaacacacc cacacataca 75120
catgcaccca cacgtgtaca cagatgcacc tccaccccca tacatgcaca tggacacaca 75180
catgcaccca cacgcacaca agcatccatg ctcacatggg tacacactca cacatccatg 75240
catgcacgtg taaacacaca cacccccaca catacacgtg cacccacaca tgcacacaga 75300
cgcacctcca cccccacaca cgcacacaca cacatgcacc cacacatgga tacacgcaca 75360
ctcacacatg tacccacacc tgtgtgtaca cacacacatg catgctcaca cacatgcacc 75420
caggcacaca caaatccaca ttcacccata cagtcacaca catgcataca cacacataca 75480
aacacatgca ttcacacaga tgcatacaca cacacactta caaactacac atgtgcttat 75540
acatgctcac atgcatgtat atgcacacac ataccctcac cttatgcaca catgtaccca 75600
cacacgtacc cacacatata caagcatgca cacatatata tatatacaca tgctcacacg 75660
catacccaca ctcacatgtg tgcacatatg ctcacacaca cgtgcacaca catgctcaca 75720
cacacactta ctgttgctca ggcttagctg ctttgggctt aagaagcaaa ctgcaccttc 75780
caaaaaatga gtgtggtgtt cagttaaaca accaaataat tctttagcac tgaatatgtg 75840
gactttagaa attcaaacta taaggtgata ataacgttgt cctgctactt tttaatctaa 75900
caaacatatc agaactgaca ctcagttcaa atgaagaaag taggaattgg gcgtgccgtg 75960
ttattttttc aaagattctc ctattgctcc aaattgttgg ggattatctt aaagtctttg 76020
aatagcttca gttatggaag attttaccct ctgagaatag aactgaattt tagacaaacc 76080
atgagtccat tgtagctaga ctggcatgca agttgggatt aaacagagta aaacgtcttg 76140
tttaaaaaaa taagaaaggc cggcttgggc aacatagtga gacctcctct atgaaaagtt 76200
agctgggcat ggtggtgtgc gcctgtggtt ccagccgctc aggaggccga ggcaggagga 76260
tggaggtcaa gactgcagtg gactgtggtt gcgccactgt actccagcct gggtgacaca 76320
gcaagacccc gtctcaaaaa aagaaaacag aaaaaagaaa aaaaaagttg agcaaggaga 76380
ctaatttgtg acatgcagct gaacatggtt tttaagacca gttttgaaag aggaattcca 76440
acattattct taacatttca gaagcctggg cataagggtg acctccaggg tgccgtgtta 76500
taacaggact gctcctttca acagctatga ccttatacca tgtcttgggg tgttgcctgc 76560
cgtgtgacag tccaatatta tacctactac ttaagttttc tttagattaa aaaatgtgct 76620
tcatatttta tgccatttct acaaatgtat agtaaaacat aaccaagaga gcttattaaa 76680
taatttcatc caaagcagtt ctaccagtgc ttcacattta ttttttattt atttatttat 76740
ttttgagact gagtctcact ctcttgccca ggctggagtg cagtggcgca atctcagctc 76800
actgcaacct ccccctcctg ggttcaagcg attctcctgc ctcagcctcc taagtagctg 76860
ggattacagg tgccagccac cacacccgac taatttttgt atttttagta gacacgggct 76920
tttgccatgt tggccgggct ggtctcgaaa tcctgacctc aggtcatcca cctaccttgg 76980
cctcccaaag tgctggcatt gcgggcatga gctactgcgc ctggtccaca tttaattttt 77040
tgcaaaaaga tgacagctgc taacagagat gaattctcat gagtgatatc attgagcttc 77100
gtaggccaca tgagtgtgtg ccgggaccag tgtggcagca agcggggcgt tctgctctcg 77160
gcatggagtg attggggaaa atctaggcag cttcctgcct cacgctgttt aaaaccttta 77220
taatgtgctt tatttcattt atttgaaatg actgcctgtc gtgtcagata tattcatagt 77280
caagcttgag tataaaaggc atattccaaa gttaaatata agctgctgca tagatttttt 77340
tgtaaaatga tctcaccaag aatgtttatc cataaagttt agcgaatttg caagtgtgtt 77400
tttcaacagc atttctcttt agctttaata aacattggtt tcttcatggt accactcatt 77460
ttgaattcag tggtctccag ttctccctgc taaatgaggc ccactttcta aaaccaaagt 77520
gataatttta taaaaatgaa atgagatatt tgttaccaca gaagtcctca tttacgagag 77580
tacatcccca tagaactagt ccacggtgag cctcaggggc atgcaagctg tttaacgatg 77640
cccccagcct agaaaggccc aggcttgggt gttcatgctc cgctgttgcc ttcttgaaat 77700
tcataatcat ctttgaacaa ggggtcccgc agtgtgtggt ggctcacgcc tgtaatccca 77760
acactctggg aggctgaagc gggtggatca cctgaggtcg ggagtttgag accagcctga 77820
ccaacatggt gaaaccccat ctctactaaa aatacagaaa ttaaccaggc gtggttggtg 77880
ggtgcctgta atcccagcta ctcaggaggc tgaggcagga gaatcactca aacctgggag 77940
gtggaggttg cagtgagtcg agatcacgcc actgcactcc agcctgggca acagagcgag 78000
actccgtctc aaaaaagaaa aaccaagggg tcccacattt gcatttttgc tctgggtcct 78060
gtaaattacg tagccaggcc tgcatttgtc ctgggagatg ctctaccaaa aaacaataaa 78120
taacaccaag cattctgtaa tcaaacactg taggaacccc tgcttatcct agcctcattc 78180
tcattctgga agactgcaca tttatcatgt taaagactca gctagggagg cccaacttca 78240
ttcaactcag tgtttcttat ttttttaaaa cagaactcat tttttaaaaa aattattggc 78300
tgggcgtggt ggctcacgcc tgtaatccca gcactttggg aggctgaggt gggcggatca 78360
cgaggtcagg agatcgagac catcctggct aacacggtga aaccccgtct ctactaaaaa 78420
tacaaaaaaa aatgagctgg gcatggtggc gggcgcctgt agtcccagct actggggagg 78480
ctgaggcagg agaatggcat gaacccggga ggcggagctt gctgtgagcc aagatcacgc 78540
cactgcactc cagcctgggc aacagagcga gactccatct caaaaaaaaa aaaaaattat 78600
ttaacacctt tatttctgct gaatgtactt tagaaagatt gagtgatttg aataaagtga 78660
cggtggccta agagtctatt ttctggaatt gagggaatac tgccatcgat ccttgaaaaa 78720
tatttattta gttcctccta gaggccgggc acagtggctc acgcatgtaa tcctggcctg 78780
cactttggaa ggctgaggtg gacagattgc ctgagctcag gagttcaaga ccagcctggg 78840
taacaaggtg aaacccgtct ctactaaaat acaaaaaatt agctgggcgt ggtgatgtgt 78900
gcttgtaatc ccagctactc gggaggctga ggcaggagaa ttgcttgaac tcaggaggcg 78960
gaggcagagg ttgcaatgag ctgggattgc accactgcac tccagcctgg gcaacagagc 79020
aagactctgt ctcaaaaaaa aaaaaaaatt atctagcccc tcctagaaat gttaattcct 79080
taaatctgag cttcagcttt ctgtgaagca gaattatctc caaactttaa caaacaatgg 79140
tcagaactgt ttttaaggtc ttggagagag atcattttca gtctttatta atcggacttg 79200
agattattta gaaacttggc tctgaatatt gtattcagaa tgttttcact catttgtgag 79260
taatttttta aatatcccct ttcctcagat gcagaatcag ggctttttgt ccagcattat 79320
gttgcaagtc ctggttctgt tgaaacattc cataccatct gtgtgatggt tatcggcacc 79380
tccaccggtg ccctgaagac agttttgtgc tgtgagtcca gaaacaggaa acacttcagg 79440
ctgtgtgtca gaagcattgt cagtggttgt gttttgccca ctggcagggg gcattcttta 79500
aatcctggga tgcttctgcg ctttgggctc cactgttcca gcagtgatta gaaataacgc 79560
tgtaggccgg gcgcggtggc tcacccctgt aatcccagca ctttgggagg ctgaggtggg 79620
cagattacct gaggtcagga gtgcgacacc agcctgacca acatggtgta accccgtctc 79680
tactaaaaat acaaaattag ctgggcgtgg tggcgcatgc ctgtaatccc agctactcag 79740
aaggctgagg cgggagaatc gcttgaacct gggaggccga ggttgcagtg agccgagatt 79800
gtgccattgc actccagcct gggcaacaag agcaaaactc tgtctcaaaa aaaaaagaaa 79860
taacacctta gcccactgca ttattgacct gtgtctgcat gagctgtgga ccacattata 79920
atcagagaga tctctcagat gttgtcactt tcctgctcta cccgcagatg taaatttcag 79980
ccaacagcag tgtttgtgct cattttcccc ggctctccca cacatgtaat cccttctgag 80040
catgttggct tcaaataata tggccagcca cctcttccac cacgagatct tcaggaaatg 80100
gcaggccact gggtttacat gcagatggca tgggagcaca caaggcacgg ctgtggggag 80160
ttggcacttg ctccagaata tggagcaccg agtgaaggtt tcagtttcct gcactgagag 80220
aaacaagggc attccgaggc ttttccactt tatccctaaa gagtttcaca acgcttgttt 80280
gccgatttct acatagatgc cacctttctg agttgtatgt atttacatgc caaatgtatt 80340
cattgagcag cgttaaataa tggtgttcac ccctaaagtg catatactgg taaaattaag 80400
aatgatcgta attaagcctc ttgcaatagt cattagttca gagaatattt aagaatatta 80460
aaggtgcttt gctaatgtcc tcgttagttt tgttttgaca aaatcagtac ttcagtttct 80520
tgtttctttt ttttttgaga cggagtctta ctctcgctct gtcgcccaga ctggagactg 80580
gagtgcagtg gcacgatctt ggctcactgc aacgtccacc tcccaggttc aagcgattct 80640
cctgcctcag cctcccgagt agctggggtt acaggcacac actatgcctg gctaattttt 80700
tttttttttt tgagacggag tctcgctctg tcacccaggc tggagtgcag tggcgcaatg 80760
tcggctcact gcaagctctg cctcctgggt tcacgccatt ctcctgcctc agcctcccga 80820
gtagctggga ctacaggcgc ccgccaccac acccagctaa tttttttgta tttttagtag 80880
agacggggtt tcaccatgct ggccaggctg gtctcgaact cttgacctca ggtaaaccac 80940
ccacctcagc ctcccaaagt tctgggatta caggcgtgag ccaccatgcc cagcccagta 81000
cttcagtttc ttagcgatga aatccaccca atgtcaggcg atgactatta ttattttact 81060
gatttatact gtttgttctc tattaatgtc ttattttccc caaccgattt tgaagttgag 81120
taaggactat gttccgcggg tatcttgagt cctctgaggc actgagcttg gtgatttgga 81180
cgcaggagct gctcattagt gagctgatag ctgggagcat agcgcatccc acatcacctg 81240
acttaccttg gtgtcctcct ttgtagcctt ttgtcataca tgatatggag acactgtgta 81300
tggctgagaa gacgctggtg gccaagctgg tggccaatgg catccagaac aaggaggcgg 81360
aggtccgcat ctttcactgc tgccagtgca cgtcagtgga gaccgtcacg gagctcacgg 81420
aattcgccaa ggccatccca ggcttcgcaa acttggacct gaacgatcaa gtgacattgc 81480
taaaatacgg agtttatgag gccatattcg ccatgctgtc ttctgtgatg aacaaagacg 81540
ggatgctggt agcgtatgga aatgggttta taactcgtga attcctaaaa agcctaagga 81600
aaccgttctg tgatatcatg gaacccaagt ttgattttgc catgaagttc aatgcactgg 81660
aactggatga cagtgatatc tccctttttg tggctgctat catttgctgt ggaggtgagt 81720
ggttgattta atctgctggt atcatgtcac tgacaggctc ctgtcttgaa aaatttgaca 81780
atgggaaatc cagtaccagc ctgagctgtt ccagtggagg ggacactcac atggtgggaa 81840
gacgtctgac ccccagtcac tgctgagaat tcagtgggaa ttataacaat attgtataat 81900
attatagtat atattgttat tatctataaa tacatattta atattatgta aatgtatgac 81960
attttaatca taatattagc caggtgtggg ggtgcacacc tttagtccca gctacttact 82020
cagtagactg aggcaaaagg atctcttgag cccaggagtt caggttgcaa tgagttatga 82080
atgcaccact gcactctagc ctgggcaaca gaacaagacc tatttcttta aaaaaaaatt 82140
atatattttg cacaaatata tatatagaga aaaagaggtc ggacatgggc ctgtaatccc 82200
agccctttgg gaggctgagg tgggtggatc acttgagccc aggaggttga gaccagcctg 82260
ggcaacatgg caagaccccg tctctacaaa aaaaaaaata gaaaaaatta gtcaagtatg 82320
gtggcatgta cctgtagtcc cagctacttg agaggctgag gtgggaggat cacttaagcc 82380
caggagacaa aggttgcagt gagccaaggt cacgccacca cactccagcc tgggcgacga 82440
agaatgaccc tgtctcaaaa aaaaaaaaaa aaaaaattat acacacacac acacacacac 82500
atttcgttta tattatatct aatattataa acagatataa tttatatatt atgatattcc 82560
tgtatatatt atataatgat gttgtattca tattatagac aatattgtat gaagtgctat 82620
acagatgtca gtatagttgc tgtcacagtt ggttatgttg atgaaaagta tatttcctaa 82680
tgcaaaatat aatatcagtc agcagccaag tggcagtgac tgcaaggttt gctttgcccg 82740
aggaagcaga tcccagggaa ggccgatctg gtcctctctg tggaagctgg ctctgcagcc 82800
tccacatttt tggctcggtg tcacgttcct ttaaatagcc ccatctcagg tctaggaagg 82860
tcatccacct actgcaaact cggctgacct tacccagggt tggtggagac agatggggtc 82920
tcccacactg cctgcagcca tactgcgcct gggggattga ctcactgtca gcatggagct 82980
gactcagccc taccagccgt gcccgttact gtgtggctgg gcacaagtca gatgaaggaa 83040
gtccttgcgc tctggcataa agtgtacaaa gacaaagcag ttatgcataa tttgtccttt 83100
agtatggtca ggatgtagca ttgtgggtaa aatgcagttg cagaactatt tatatgtagc 83160
atgatcacag ttttataaag gaaattataa tcctatatca atcctatgta tatagaaaaa 83220
tgtccagtga gatatatgtt aaacctatta tggtgggatt aaaattatga ggggggattt 83280
ctatttttca aaagattcct cctttttttt ttttttgaga cagagtctcc gtctgtcacc 83340
ctggctggag tgcagtggca cgatctcagg tcactgcaac ttccgcctcc tgggttcaag 83400
tgattcgcct gcctcagcct cctgagtagc tgagattaca ggaacatgcc agcacacctg 83460
gctaattttt gtatttttag taaagatggg gtttcaccat attggccagg ctggtctcaa 83520
actcctgacc ccgggtgacc cacccacctc ggcctcccaa agtgctggga ttacaggcat 83580
gagccactgc acccggcaat aattcctctc tttagagact taatagttat agccccagcc 83640
actctggagg ccgaggcagg aggattgctt gagcctagga gttccagtcc agcctaagca 83700
acagagcaag accccatcac taaaacaata caaaaacaag aattttagaa ataaaaactt 83760
aataattaca tttacaacca aaaacaatga agatgtttaa atcctcatca ctagcaaccc 83820
tgttaagaat catagtaatg actgggtctg taagggagca ccgcctgctg aacatggctc 83880
agggcagtat tttctggacc aagaatcagg tctcatgctt tgagactgtc ccaggatgtc 83940
tagtgccagc taccccaggc aggtcatctg gtgtgaatgt tgactcttcc tgcaccaagt 84000
ctcagacctg ccccaccctc ctccccactc tgggtctcct gatcttggct cactgcaatc 84060
tccgtctccc aggttcaagc gattctccca cctcagcctc ccgagtatct gggattacag 84120
gcgtgagcca ccgtgcctgg cctacaaaac ctagttctaa cacaatcact ccttaaatat 84180
ggtggaacac ttgaagcttg atatctagtt tggattcaaa agcttcattt cccatattat 84240
gcaaaactgg tggttgtgat ctccagaatg tactgttcct cctactagct ctaatttttc 84300
tccctgacag gtggtcatca ggtaaatcac aagtgaaaag gccgcaccat aaggtgtact 84360
tagggcacta ttgccgccta gtagtatgaa tatttaggaa agagtactgg tcctgtctgt 84420
ccctacttca cctattgact ttggaaaaac ctatgtctat cttccagtca agttgacaat 84480
atctaaaggc agctcagttt ttttctaaga aaggccacat aaaataggca tgtttggttc 84540
ctgaaactga taagcagttc ttgggtgatt atcacactca aacctctctc tcttctttcg 84600
agactagatc gtcctggcct tctaaacgta ggacacattg aaaaaatgca ggagggtatt 84660
gtacatgtgc tcagactcca cctgcagagc aaccacccgg acgatatctt tctcttccca 84720
aaacttcttc aaaaaatggc agacctccgg cagctggtga cggagcatgc gcagctggtg 84780
cagatcatca agaagacgga gtcggatgct gcgctgcacc cgctactgca ggagatctac 84840
agggacatgt actgagttcc ttcagatcag ccacaccttt tccaggagtt ctgaagctga 84900
cagcactaca aaggagacgg gggagcagca cgattttgca caaatatcca ccactttaac 84960
cttagagctt ggacagtctg agctgtaggt aaccggcata ttattccata tctttgtttt 85020
aaccagtact tctaagagca tagaactcaa atgctggggg taggtggcta atctcaggac 85080
tgggaagatt acggcgaatt atgctcaatg gtctgatttt aactcacccg atgttaatca 85140
atgcacattg ctttagatca cattcgtgat ttaccattta attaactggt aacctcaaaa 85200
ttcgtggcct gtcttcccat tcaccccgct tttgactatt gtgctccttt ataattctga 85260
aaactaatca gcacttttta acaatgttta taatcctata agtctagatg tatccaaagg 85320
tgaagtatgt aaaaagcagc aaaatattta tttcaaagac ttcacttctg tttcctgaat 85380
ctaaagaaag acaacatgct gctttttaat cataggatgg agaattttaa agaactgttt 85440
gggccaggca cagtcgctca tacttgtaat cccagcactt tgggaggccg aggcgggtgg 85500
atcacaaggt cagcagatcg agaccatcct ggccaacatg gtgaaaccct gtctctacta 85560
aaaatacaaa aattagccgg gtgtggtggc acatgcctgt aatcccagct actcgggaag 85620
ctgaggcagg agaattgctt gaaccaggga gttggaggtt gcagtgagct aagactgcac 85680
cactgcactc cagcctggtg acagaacgag actctgtctt aaaaacaaac aaacaaaaaa 85740
aaaatctgtt agataagcta tcaaaatgca gctgttgttt tgtttttggc tcactgtttt 85800
cgtggttgta actaatatgt ggaaaggccc atttccaggt ttgcgtagaa gagcccagaa 85860
aacagagtct caagaccccc gctctggact gtcataagct agcacccgtg gtaagcggga 85920
cgagacaagc tcccgaagcc cgccagcttc ctgctccact cagctccgtc cagtcaacct 85980
gaacccaccc agtccagctg tctgtgggaa tggtggtgtt cttagggaca gactgacacc 86040
ttacttgtca gtgttcctcc gggccccatt tggcagctcc cgtatctttt gttatgttgc 86100
ttttaaagat atgatgtttt attgttttaa ctcttggtga cagtagatgc tctctggagc 86160
gcagacgagg cacatgtgtc ttcatagcct gggctgggtg ggagccagtc accctgcgga 86220
tcgagagagg gggtagagtc ttcttcaaat ggcagtttta cttcaaatgg cagatttcac 86280
aagagttggt tattttttac aatggtttag gttgttaagt ctcctttgta tgtaaggtag 86340
ttttttcaac atctaaaatt tttgttttag ccttcaaaac caacttacca acctcagtcc 86400
agctgggaag gcagcgttga ttatggtagt ttgtcaagaa tatatggacc tggaaacact 86460
ttctctctct gtccacctgg tagataaatt gtcctgttga gaatttttag atctggactg 86520
gaactgccag gaccaccgcc tccagggagt cgctgggcac ctggaggtat cgtcgatgcc 86580
tctcccccat ctttagaaaa tttggctctt ctgaggtcat tattatttta agaatgatta 86640
ggattgataa gggtcccatg accagcatta tgaaaatgcg agagtgggaa ggacacagtg 86700
tgagacttcc actagaaaaa agtgaaagtt agggttagga catccttttt taaaaattac 86760
aaatttagtc cgttttggtt tttgtaatca ggctaggcac agtggctcac acatggaatc 86820
ccagcacttt gggaggccga ggtgggagga tcacttgagc ccaggagttc gagaccagcc 86880
taggcaacat agcaagaccc tgtctgtaca caaaatttaa aaattagttc atcggggtgg 86940
cacacatcag tagtcccagc tactctgcag gctgaggtgg gaggattgct tgaacccagg 87000
aggtcgaggc tgcagtgagc tgtgatctca ccactgcatt ccagcctggg tgacagagtt 87060
agattccacc ctctcccacc ccggcaaaaa aaaaaaaaaa agatgcaatc aaaggggctg 87120
ttggccagca atggcagcag cagcggcggg cagtctgccc aagtgtctta ggaaccaaaa 87180
gcaaataaaa gtgtttccat atatgccacc agccaagtgg ccatcctaat tcagaaagaa 87240
gctagccttt gagtgtctgt catggtgcat ccgtttcagt attatttcct aaaatgagaa 87300
gcccctgtgt caacaagatc caggggctgg agcccaatgc caagcctgtg ttgtccccag 87360
cgaccctgca gctgctcgct ctgatgtacc ctgtgccatt caaggagatg tggtccagga 87420
aagtgagcct catggttttc agagaagtca ttgttctgtt tacattttca taaaacctgt 87480
ttaaaatagc tccccgtctc aggctttcag cagtaacagt gagctgactg gcaagttcga 87540
tgttagctcc cgggacactc agcagcgatg gtgagcattt tggtttcctt aaggcccagc 87600
aagacttcca gggacatctc tggtgaagcc agaatggaga cacccgtgac ctcaggctga 87660
aagtcactcg acattggtct cttgtgttga tagggaagga aatcaggcat tcctatttct 87720
ttaaataaca aaaccactaa ttgccactca atgctggaat attttgggtc acctaatcat 87780
agatttctca gggcatcaat actcaaatat aggctgatta tgccccagtt caaatgggaa 87840
ctattaacag agtgcatttc ttgcttgctg ggtttcaaca gacatcagcc aaaagaacaa 87900
aagagatgtc aggacagatt ccaggagtgt cggagcacat gtgtggcacc cgctccctct 87960
ggcagcgaat gtaggaagtc gccaaattta cccactcttc aacaagtcat tgtttaaaca 88020
cggtttttca ttttctcaac ttttaatagc aaaaagtgcc aaagtcctca gagacctaac 88080
agccttggtc taccgtgctg accagggtga aggcacggcg agggactcct cccagacgtg 88140
cctcttgtgt gccagctggc tgtggctcgg gagcagacgc aggcctctcc attgtccagg 88200
ggagcctggc ggcgcatccc tcctctccca cctcctggca cttccagctg ggtgtcccac 88260
atgttggatt ccgtccccac cacacttcca gagaccggag aactgtgcag ggcctaaggc 88320
cgtttggatg aattgtcaaa acaagatgct tccagttaca gcggcaggag cgggactggg 88380
agcacgggct gacggctgct ggtgcctttc ttcccacctc gcttgcctgt ttccgcttga 88440
cccttcctcc agctccgatg agaagagtat aaagcatctt cctaacgggt gtgtttgcta 88500
tacgaacata atggacgtga agtggggcag aaacccagaa ctcagcattc aaggatgccc 88560
aggagagctg tccctgtttt aaagagctgt gttttgtttt gtttcgcatt tagagagcag 88620
acaaggcacc cttctgctgc gctgatacgt ttcttacact gggccatttt agacccccag 88680
ggaaacagcc ttcctggagc gttgtctgga ggttccaggg acagggcagc ctcccagagc 88740
cgagcaagag ctcaaggtac aaatgagaga tttgctatac cgtgagaagt caacaactta 88800
gccaccactt ccccgcaatg gaccatgtaa caaatacctc agcaggccct gcaaaaggcc 88860
atgctagagc tgaggcgcac agcctgtggc ctctgtagtt agggcaggtg ggatggagac 88920
tccttgagtg cacacacctg agcctgccca cacacagggg agcagcatct cgtatgacgt 88980
ctggaaggaa cttcggttgt gtaaagggag ccttgaagat acgtgcaaaa ggtgctaccc 89040
caatttggtg aaactgacat tgggcacgtc ttgggcttag gagaagcggc cgatggtccc 89100
ggcctgcagt gacaaacccc cctccccgca ccgcccccag caccccctct cctcttcacc 89160
tcttcctgct ggccacgagg aagccacttc ctcagagaga ccctaccaga tgcggatgga 89220
aacagatgca ccaaagcaag ccctgatgaa accgcgactt cctaaggtct gtctcctctg 89280
aacttgcacc tgggcctctc tgtgtttggt tccaagcact tcccacctca aactcccatt 89340
ttcaaaccac tgtatctctg cgcacatctg ctacttacca gccgcataca tgatggaggg 89400
ttttttggtc ctgatccagt ggccacacct gtctttgaaa tgtctcactg aactccagtt 89460
ttaaaataga ttcattgctt caacacagca agcccaatgc acccagctaa gactggcttg 89520
accgacagcc tggcctttgg tggggggctt cctggggcct ggggaaagct ggccaccttc 89580
aacagctggt acctcttcaa cagtgtggcc tttcaaaatg cagatgccac caggagaaca 89640
tgcccacagc tcaccaccta tggatgccat ggctctgggc agctttcaaa gcaggttcct 89700
gtggtctcct cagctgtttg agggggtaac agcaaatcag cctccatttt aaaatgaaaa 89760
caccagcctc cagatgtagg gcctgctggg tgttgctagc cgctggtccc caggcacggt 89820
gcactttctc cacctcctgc agcctccctg ttgtttctag actcttgcac ctggtgagtg 89880
caaggatagg tgacccaggg gcctgcagcc ttgtcctcag ctcccatctc ctggactgcc 89940
agcctcaccc tctgcagtta gcatggttgg cctgatgcag ggatcccgag ggattacttt 90000
ttagaccttc tttcacattc agaaaagtag tatagattca ggagaggcaa gaaaattatg 90060
ctgtccatag aagtcaccca tgaagactga tgccaccacc tgaaggctca tgattgttaa 90120
aaatgtccac gggaacctct cgtccacagg aggtttgtct caacacttcc catttttacg 90180
gcattggcat tgccaagcat ggggaagtat ctgctcttct catgttaaaa gtggcccagc 90240
ttttcttaac tcagtccaag ctgacttgtt tagctgcact ggaatttctt accaaccaaa 90300
tatttgcatc gagcaaaggg ggctgtgtgc acctccctaa tggcagcgat gatggctgct 90360
gtcattcaag cccatcttca gacgtcacag tctggaagtg aaatgtccac aaacatctgt 90420
ggcagaaaag gctatacgga ccacccagtt gtgctgcagc tttacagagc aaggaagggt 90480
tgtggcaaat aaatgattaa cctgcctcga ctgtgctgag ggcaacaaag gccatctcac 90540
caaaggatta ttcgatgcca ttaaatcatc ccgtgacctt cctgcttccg agtccatggc 90600
ctttgcccag ggcatgtact cccctgagag gccttctgcc tagaaagatc tatgactggg 90660
ttccaaagtt gaggcctagg tttttgctgg gatttagata ttttcaggca ccattttgac 90720
agcattcagg aaaacggtta ttgaccccat agactagggt aagaataaag gcaataaatt 90780
tggtctgact cagaatatag gagatccata tatttctctg gaaaccacag tgtacactaa 90840
aatgtgaaat tgaaggtttt gttaaaaaga aaaagataat gagcttcatg ctttgtttaa 90900
ttacataatg atttccatta cgctatttct gtgaaatgca gcaggttctt aaacgttatt 90960
tcagtggcat gggctggaag cttatcacaa aaagccatgt gtgtggcctt atcagaacag 91020
aaagagacag gctggtgccc aaggctgctg cctgctccac cttttgccag ctctggacat 91080
ctgaggacgt cccggcagat ctggaatggg gccctcaact gaccatttgc ttctcagaat 91140
ttcagtttga gacatgagag gtataatcag ttacttttct ccccccagag aaaccctttt 91200
gtgaggggag aggagctatg gtatgtggtt cagctgaaac acatacaact gcatcctttt 91260
ggagtccttt gccaacaaaa acagaccaac agaccagatg gtgtccatgt tcaatatcat 91320
gtcttgatgg acgcagctga tgacctcaaa tacttgagtg gtctcatggc tgttagatgg 91380
attatttgaa aaaaaaaaaa aaaaaagaga gaaaaaataa ttgattttta catcagagat 91440
agcaaactaa gacctgggga ggggggtcag cttttatttt attttatttt ttttaagttt 91500
gctagttggg tcaaatgtga ggaggaggga gtctacctgc cacctcttct cttgcccctc 91560
ttctgcccac acatccagca tccaaaatcc attcatttaa tgaattgata aagtgccgtg 91620
caaactggtg cacaaacagg cccccagtcc acgcagcctg gctcctagga aaagtggtga 91680
ccgggcgtgg gggggcatgc cgcagccctg ggacacagtc gggcaccttc cccggacccc 91740
caggccttgg ctgtgcctca agtcagagag ggtcagcctt caggccccgg agacgagtga 91800
ctggccgatc atttcacaat aaaatcactc acttttggca acttcacttt ttttaaggca 91860
cagtcagttc cttttctcat gtacctcaca aaagatgaag accatgtagt actctttttg 91920
gtaaagttac agtgttcatg ttaaatatca cttttttcta cattgtgtgg taaaaagaac 91980
tacgttaata gctatatctt aaatactgtg atttgacttt ttgaaaaata tcctaataca 92040
aatattttac taacttacaa tcactcattt aataagaaac atttggattc ttttgaaatc 92100
agtgttaatt gactcatatt cttaaaagcc tggctcttga ccctattgga aacacaaagg 92160
aagctgaaat caaacatcta aaatacactg cgtacacgtg tgcgtgcaca cacacacaca 92220
cacacacaca cacacagctc ttcatttctc ctgagccatg cagaatttac tttcaatgtg 92280
gaaatctgtt ccctttacca cactgtatat gcacagagca caagagaggc tatctctagt 92340
cacttccacc agcgaggcct tagactccgt attagaggcc accgatttca tacaacagtg 92400
tttcgctaaa gacccttcac tattcttgtt tagtaaatag ctgtctgctc ttcagggaac 92460
tgttacctat gggttattac caaagaacgc tggcaattgg aaatgtcctg atggaaattc 92520
tttgcacgtg ccggttctct ggcatcctcc aggtggccca acccaaagca gaaagcagaa 92580
accacagacc ccgtgagtct ccccatacct tgtttccaat aacttggcaa aacttcttgg 92640
tgcatattgg ttacaccctc tgggattcat aatgccatta ggctaaaacc ctaagagaga 92700
gggttgacag aaacacacgc gagaatgagg cagatcccag agcaaggact gggcccagac 92760
tctccacatg tgctctacta gtgagtgcct tatactctca gtattttggg gcttacagct 92820
tcttatttgt gctaaaaagg tgcagttcca aagtaggaac tgccacacag gccccagcat 92880
cctctctcca acttcatacc tctctcctgg tggggggagc gggcatccag gacctccgga 92940
atcaaggatg tgcagagaag agcgaaagta atttttctag tcacatgaac tgattggttc 93000
caggcaatta gaaaatggct ataaaataac cttaatttta aaaaaaaatc ttgggtcttc 93060
gttttcctat taggagactg aactgaccac atgtattgat ttatatcctg aatatatggg 93120
aacttctgtg tttgggatgt cctactgtaa gactgatgaa tgtacagagt taatttcagg 93180
gtacagtttt gccttaatgg ttttaaaaaa taaactattt tttaaaattt t 93231
<210> 3
<211> 15496
<212> DNA
<213> 智人(Homo sapiens)
<400> 3
ggctccaccc ccaagccagg cgaggcaggt tccgaggttg gaacacctgg cgagtcctcg 60
gtgtcggtgg ccggcagtca tctcgcggcc gttcaggtga gggggttgga ggagtggctc 120
atgagcgagg aagggggagc aggcgggctc ccacccggtg ctccgtgaga tcgaggggag 180
cgggttctgg gtgcggatgc acgcgctggg cgggacgctg gcagtggtac ccgagacggg 240
gcggaaggag actggagtga aggtgggcct aggctaaggt acgtgctaga aaggatgaaa 300
acggagtgaa attcttaagt gatggaacta ggctagggca tgtttcttgc cctttaaaat 360
gtgttgtctt cgggagacag gacgtagaag atagttgcag cacagggtga taggctggcg 420
aaagttatac aaaagcagga accactagaa ggaggtaaga tgtagtgtgc tttgggagta 480
gtggggttgg gaagggcgtc cgagaggagg ttactgaagg atgactagga gttgaatggg 540
aggacatcac ctgtaaggga acgatatttc cgtgggcaga gaggaatgaa gcagtagcaa 600
ccatgagtga tcagatactg caaaaatgtg aagtgtagga tggcgagaat gtaagaaatg 660
aagagtgaag aagtctggaa gggcctcgtg tgcatcaatc acagcggggc ttgatcttta 720
tgcttagggc aagcactccc ttgaactttg agtgttttaa ggaggttatc tctgatgttt 780
aaatttatat agatcgtggc attgcatctt agaaataagg tttaggaagg gcaagcttgg 840
aggcagggca agtccagaaa atgaaggagc tggtgaaatc cgtgttaaag tgccaaagga 900
cagagactgg ctgacagcta aacttcaagg tttctgagaa tccacaaata actaaattta 960
tctagtcaac ctgttccaga acaggcttcc agtcatttag gttgcccaag aatgagtaaa 1020
ggaaaaggaa attcaatttt ccaagacctt gtttcccctc tcctctttaa ttccttgttc 1080
ggttagcaac agtatatcca ttccctcgct cctttgtgaa aagtaaattc ctgaatgtta 1140
actaaaccaa gtgtttctaa attgggtaag agtttgaaga cttaaggcag cagaatggga 1200
gagacttaaa acgttatgtc tgagaattag gcattaaagg aggcctagta tttgggcggg 1260
ggttgtgagg agcacatact gaacctttgg acctgttgag tgagttcatg tgcctctgaa 1320
ctctctgact ggatatgacc agtaaacttg gataattaga tcctggagtt taggggagag 1380
ggctagagat agagatgatg gatgtcagca tatttttaaa acagaaaata gttaagatca 1440
cccaagacaa tctggaatcg ttagaaggga gtaaggaagg cattattggg aaactttcca 1500
gcttcaattc tcatattttt tctaatctcc tggttgagtc tttggagttg ctgttctctc 1560
tatgcaaaac ccctcccttg accctctctc cctcactcta ttttttaatt tgtcacctcc 1620
ttctcctgtt ctaggtctca gtttagatag cacctttctc tagaagttca tagcactgtg 1680
tattcccccc tttattgttc ttatcacata atttttgatg gtttggacac tagttgttat 1740
tcctcactaa attttatgtt ttatgaactc aggggtaagg gcaccagcta gcacaatgaa 1800
tgcacaatac ttgtcagagt gaatgcattt aagttccaag aaccaaggaa aggcggtatt 1860
tcaagaagag aagtatcaaa tcttccagat tagtcaaata aactccaaaa aaaaaaaaaa 1920
aggtttattg gatttggcag ctggagatcc atagcgattt tttttttttt tttttttttt 1980
ttttgagacg gagtctcact ctgtcgccca ggctggaatg cagtgtcgtg atctctgctc 2040
gctgcaacct cagcctcccg ggttcaagca attctcctgc ctcagcctcc ccagtaggtg 2100
gaattacagg catacgccac cacacccggc taattttttt gtattttttt ggtggagatg 2160
tttcaccata ttggccagac tggtctggaa ctcctgacct tgtgatccgc ccacctcagc 2220
ctcccaaagt gctgggatta ccagcgtaag ccaccacacc cagcctcctt agtgatttta 2280
gtaagagtaa gttcagtgca gtgatgacaa tagaatgcag attgcagttg ctagaatata 2340
aacaggaaat aagaagataa agacaactcg tggaatacct tttcatagag cttaggtaaa 2400
ctgtaggaat tattctcctt gtactctaat acttattatg ggttttattt ataattatag 2460
tgtaatataa tggatgagtg catgggcttc cccacttagc atttgttaag cattaactta 2520
acattaagca ttagactttg ggcaagttgc ttaatctttc taaacctcag ttattttatc 2580
tataaaatgg tgataaaata atacctacct cacgaaggtg tggtaaggat taaagtgaaa 2640
atgtagagag caggtagcat gctttgaaca cagttcttgg cacagaaagt gcccaataat 2700
tgttagtttc ttgtagctat tacatgccag gtcctgtgct aactaagcgc tttatatgca 2760
ttgtctcttg gactcattgg aagacctact gttttaattt ttgctgctga taaaactgca 2820
tcacagagag gttacctaat ttgcccaagg tcacaggaca ggactagtaa gtggtcttgg 2880
ttcattattg tcaaatttac taatcacctt gagaaaaatt aagattggat ggttgcctta 2940
ttttacaact tagaagatga ttgaagacat tttggtgcag gtggggagcc agattgcaag 3000
tagctcagtg agttgtgtgg gtgagttaag caaccttttt tattcttttt ttttgagacg 3060
gagttttgct gttggtgccc aggctagagt gcagtcacag cttactgaaa cctccacctc 3120
ctcatttcaa gcgattcacc tgaactcctg accttaggtg atctgcccgc atcagcctcc 3180
ccaaggtgct gggattacag gcgtgagcca ccatgcccag ctgagttaag caatctttat 3240
gtagagctct cctttgagaa agaagttggt tggttcaaag aaagataaat gggacagtgg 3300
cttggaagag gtaatggagg ctaggaaggt gtttatcaac aaaggaagat gtaggctggg 3360
cgcagtggct cacacctata atccccacac tttgggaggc tgagatggga ggattacttg 3420
agcctaggag tttaagacca gtctgggcaa catagggtga cccctgtctc cacaaaaaat 3480
taaaaaaatt agccaggcgt ggtggcatgt gcctgtggtc ccagctacga ggggctgagg 3540
tgggaggatt gcttgagcct gggaggtcga ggctgcaatg agccataatt gtgccactgc 3600
actccagctt gggtgacaga gtgagaccct gtctcaaaaa aaaagaaaaa aaaaaagaaa 3660
agacgtgaat gtgtttttag acctgaagga atggattcca tgaagggaga aggatgaaag 3720
atgggaaagg ataagtgatg gacaagttct tgaggtaaga taagaacaca ggaagactag 3780
tcagtcttag aggaaagaat gaatgagcaa agaaatttta aggcctgtaa tgacacagga 3840
tggaacacta tagtcactgt ggtgtaagtc atttgagatg agtaggacag aaggaggacg 3900
gcctgaagtg aattcagatg cctggaggag ttggctaggt tctcaatatt ccttctgtag 3960
aatgggataa aaggtcagtt tgagaagtgt tggggaaggg gacttttaaa gcactattta 4020
gaatgcttct gaggctttaa aatactcatt tttaaaatgg tccaaaaaat tcataaatta 4080
gaagcagcag tggtgaacat ttttaggaaa gtgacccttg agaagtttat tttttggtta 4140
gtgacctatt gagcttattt attaggtaag tagaacatgc tcatttaaaa agtttaaatt 4200
gtgcaaaaga catatgtcag attttttttt ctgtcttcca taacactatt tcctaccccg 4260
ccgcgctctg tcttccgtaa cactctcccc taccccgtcg ccactctgtc ttccataaca 4320
ctgtccccta ctccaccaca ctgtctccta ccccgccgag ctgtcttcca taacactctc 4380
ccctaccccg ccacgctgtc ttcattaaca ctatctcctg ccctgccaca caactctgtt 4440
ttcctagaag tcaccagtgt gaatttttcc ctttatccat atgtacattt tttgtttctg 4500
tgtgtctgtg tatatacata tgcataaaag tgcatagata aaatacatat ccttttcaaa 4560
aaatcttaag tggggctctt gctatgcata ctgttctgta acttgttact tggattaaca 4620
ctgtatctta gacatctttc tatgtagagc gtatagatct tccctgttct tttaaatggc 4680
tgtataattg tctatggaag gacttaattt atttaaccca taccttgttg atggcttatt 4740
tgtgttttgc ttttattttt tcctctttgt ttttgctgct acaagcaatg cttccttcca 4800
tcttagcgga tctgtctttg tacccttgaa tgagaaagtt gctggatcaa aggatgtatt 4860
cattttgaat taggtgttgc taatttttcc tccaatgata cactgatgta tcccccctgc 4920
ccacagtgtg tggtcatgcc tgttctctca ccctcttacc agtactggac attaataagc 4980
ttttaaagat ttgctactca ggctaaaagt gtctctttgt tttagggtgc atttcctcat 5040
ttaatgaagt gaagattctt ccttgtttag tgaccatttg cctttatttt tctgtgaact 5100
gcttgtgaat ggcatttgtc gttcttctgt tgtcttttta gtcttttttc taaagcacac 5160
tttgtagccc tttgttgtaa aatgttggaa atatttttcc cagtttgtca tttaatcttt 5220
gactttgtct ttctattccc cagtaggagg tacttaattt ttatatactc atatttggca 5280
ggctttttct ttataggttc ttttggcttt aagtgatact tttaaaccca gctattgctc 5340
atttaaatta gaaccttttc catgagaacc acactgacga tttctttaaa tatagcttga 5400
aaaaattttt cccctattgt tcttttagct attgttcttg aaaataatgt gttttttaaa 5460
ggaatatcta caaatagaaa tggtgatgat atccagcaaa tgttttaaaa tggtgtaaaa 5520
ccatttgtac tcctttagta attttttggt aaaaaattta tactccttta gtaattatca 5580
tttttaaaat gatcagagga tgcatttttt aactgtttta ttttttgaaa gctcattgtt 5640
taacttatta tatatgtatt catttctaca gaattataag gctgtctgca gagatttgaa 5700
aaatggcaac aaatgaaagt gtcagcatct ttagttcagc atccttggct gtggaatatg 5760
tagattcact tttacctgag aatcctctgc aagaaccatt taaaaatgct tggaactata 5820
tgttgaataa ttatacaaag ttccagattg caacatgggg atcccttata gttcatgaag 5880
ccctttattt cttattctgt ttacctggat ttttatttca atttatacct tatatgaaaa 5940
aatacaaaat tcaaaaggtg agtataaggg actagaaata gaatattatc attaatgttg 6000
ctgaatattt taaaagtaca tagggctttg ttttgtgagg ctaaagcagt gatatccaat 6060
agaaatatga agccacgtat gtaattttaa attttctagt agaatacata gaaaaggtaa 6120
aaagaaataa ggaaattaat ttcataatgt gtatcattta gctcaataaa tgtaaactat 6180
cgctgggtgc agggtccatg cctgtaattc cagcactttg ggaggccaag gcaggaggat 6240
tgcttgaggc caggagttca agaccatcct gggaaacata gcaagaccct gtctctacaa 6300
aaaagataca aaaataccca ggcatggtga tgtaagtcct agctacttat gaggctgaag 6360
cagaaagatt gcagcactat actctagcat aggcgacaga gtgagacctt gtctcaaaaa 6420
aaataagaaa taaatgtaaa ttattatttc aatcagtaat caaattctaa aaaatactta 6480
atgagatatt taataagtct ttgcaattcc gtgtgtattt tacattaatt ttagtctatc 6540
tcaatttaga ctagccatgt ttaaagtgtt tggaagccac atgttactag ttgctcctga 6600
attgagcaac acagtcctag gtcattattg ataacatttc aagaatactt tgttaaattg 6660
ggctttaagt agatgtgatg gttatctaac ttaagtttat gaattttaat gtttaagcta 6720
gctggaaagg aaaggtgtgg tgatttgcgc atattttgca gttcacccca actctatgtt 6780
ccagtaaatc taagggactg ttaatacact acgaccttga tcagggctat tcaagttttt 6840
tttccctaaa tatatggtag gtagttctgc agcattcgta tcatcccaaa taaggaggtg 6900
atgctcctcg tttctggata tttgcttcat tgcactaaat gttgagaggt cgctatgtac 6960
atgacaaggt gaaatctcat atgtagcctg tgagcttgac gtgagaattt ggagtagctt 7020
attagaaaga tgaattattt gttagaattt gtaagctgat gatagtttct agtgtttgct 7080
gtttactttt cataaaaagt cattccaaac taaaactcag gggcacacag tcttggtaga 7140
aagtagacca ttgagagtat tcatctatgg aaagtaattt acattcactt agtacaattg 7200
gccctccata tccatgggtt gttgtatcca tggatccaac caactgcaga tcagaaatat 7260
tcaggggaaa aaaattgtgt ctacactgaa catgtacagt cttttttttc cttgtcatta 7320
ttcaaaatga caactattta tagagcattt gcattttatt aagtattata agtgctgtag 7380
agatgattta aagtatacga gaggattcgt gtaggttatg tcaaatacta tgtcatttta 7440
tatcaggcac ttgagcatct tcagatcttg gtatttgcag aaagtcccag aaccaatcct 7500
caaaagatac caaaggacaa ctgtatatat tttggatggc agtctgtaca cattctctgt 7560
tatcattctg ttagtttcac agcctctccc agagtctcac tttaagcagg tattaatatt 7620
agtcctctct ggggataatg caggggtcag atgactgtgg actccaggcc aaaggagaaa 7680
agagcaaagg gtaaaggcga aggaaataaa aaataggagg gccaaaggag agtactctgt 7740
gaccctcaat taaggtcaca gaagctccaa agtgcttttt aggaaagcag ctgctttgaa 7800
aggcagaatt aagtttggac gtctaagttc taatgcacct ttagggtgat tgtggctgcc 7860
gtgtttcacc cagtgattta tttatagggc ttattcattg taattcattg tatggctggc 7920
caggcaaaag catccttttt ctccttcact gcagtttgta actgactcac tggttagaag 7980
tagtaacctt tgcagagaga caaaggactt tctcaggcaa gggtatatga gcagctttaa 8040
aatataatgt ggcaaaggaa agaataagct gtagtctagt tggtcagagc tagttgttta 8100
tgaacagatt gtaaggctgg ataatttgac ttcaagtctg tactcagcaa gtctttatgt 8160
ttcataacca ttaaagtcca tgctttgagc atttttgata aaaaatgtga ttttaaacca 8220
ggactagttt tcacaagtta aaggagtttt aaaagaaacc aaaatattgg tacaaattaa 8280
ttacaggttt atgcatttcg aaggcagata ccctgattaa cattgagggt atcaattgtt 8340
taagataaaa tatttgagaa ttatatttaa catatgcaat aaatgttttt attcttaaaa 8400
ttgtcgaaaa gaatagaaga agttggtggt ggtgatgaaa tagtactaaa gactttctgc 8460
tttcaaacag aacagacaac tggagagcta atgcacatcc ttgctagtta ggcgaaaatt 8520
tcacaggaat gaaaaagtaa agcagacttt gcaggatcta tttctttaaa aaaaaaaaaa 8580
acatacatct tagtaattct ccaaaaattt tcctcaaaga taaatgtact aaaaatatta 8640
tttctgaagt ttgtggccct tgtaaaggta ttcctttata ttaagtacag ttatgcataa 8700
agaaagtaaa atatggtaaa ctttcatatt gcactaggta tgaatttgta ttgctaactg 8760
tctttgtaac taatttatgt atactgtaaa tggtatagca tgtgatttta ttatagttga 8820
ttaactttgt aatttctgta actgcatcga tatcccagtc tacctggaaa attaagtcta 8880
ttaaccatag ttgctgtagg agacagtact attgccaact gaagcctgaa tccttcattt 8940
attttgtccc caattacaga gtggaggttt agaggagtgg ggttagataa tgctcagatt 9000
agaaatacaa aggcagctgt cagatcctcc cattttattg ttgaagaaac tgagttgtaa 9060
acatcacaag agctagttaa ctggtgagta gcagccctgg tattagagca caagtctctg 9120
gattgattct tagttcagtg cttttcctat ttttgtcagg aagataaccc ttaaagaatt 9180
tcaagaacag agctggatct ggagacctag attttagtta gtccaacttc tgctaataac 9240
tgcgtgtgtg accctgccca agctggttga cctctttggg cttctgctga tgcgcagtag 9300
ttcccgtact ttggatatcg tggttcaatt aaaagagttt tgttggcgga tacctgaatt 9360
tttcagcagt gacatttaaa acaaagcaat aactgatatt tattgtcacc atcgttttgt 9420
taagcccaaa gcactttttt aagtgcagtc ctataaattg aatacattta gttagtgttt 9480
gttttgtttt gctttgtttt ttataatgac ttgctaagca aatgggtatc ctgatgaggt 9540
cttaacgaac atcccatgtt gatctaactt ttctcatttt gacttgaatc tgtgaactcc 9600
ataatcagga catatctgtg tacttctcaa ctcagagagt ttataattct gtcattggat 9660
ttgaacaaaa gtgcatttat ttgttggaat gaataccact gagtgcctgg aagcatcgac 9720
ttactgtgta aaaggcttcc aatgcttcgt atacaacttc ttcaattgtg gacacccaac 9780
agtaatctta gcatattata tttcttcttc tctgaaactt ctggtaaaag aagtgaagtg 9840
aatgatctgt ggcagcaaag actggagaat tattcattcc atagtgtttc ttagtttgtt 9900
tgagatcatc atggctaggc gcatctgtta acagtttctt cacctgaagt agtgatagta 9960
gttgtcaaga atttagaagg caaagattcc tgagtcttag ttatataaag ttaacataac 10020
tgacgtagaa ttaaggtcca acataaacag agaacaaatt aggtcaagtt aaactctgat 10080
agcagagact aatattagat attgtgattt ttcttcgtag gataagccag agacatggga 10140
aaaccaatgg aagtgtttca aagttcttct ctttaatcac ttctgtatcc agctgccttt 10200
gatttgtgga acctattatt ttacagagta tttcaatatt ccttatgatt gggaaagaat 10260
gccaagatgg tacgtagata aaaatttggc ttttacaccc aattgtggct tattcagtta 10320
agttatactt aatgtttacc cgttttctta attttagtta atgtttgttc taaactttgg 10380
aagtaaataa atagtagaaa agtaaaccac agtaaaatct taaaatgttt ccatttttac 10440
atcttttaaa tattttattg gaaggtgagc ttctagtatc agaagtttcc ataacgtctt 10500
ttgtatgttt atatacatgt ataagtgctt atgttgacaa aaatatatta cattttaatt 10560
ttaaaatgaa tgaaatatat gagaatcatt tatgaggttt atagaaattg tgtttacatg 10620
aacaaaaata tgtatgtgta tatatatata tatatatata tacacacata tatatataca 10680
cacacatata tatactcatg cgtcacttaa cggatatctc ttgagaaaag tgtcatgagg 10740
caagttgtgt gaacattgta atgaaatgaa attggtctaa tgggcagtct ctttaacctt 10800
atatcaagtt atgtagctgt atctggtggt tttgagaatt tatttatgaa tatatccaat 10860
taggtcaacc tggtaagtgg gtgggtggtt ttatgtaatg tctcaagcag tgatcccaac 10920
taaaagtctg gatagtttaa gtaaaaatta tttcttacac attacaacat ttttatctta 10980
aaggtatttt cttttggcaa gatgctttgg ttgtgcagtc attgaagata cttggcacta 11040
ttttctgcat agactcttac accacaaaag aatatacaag tatattcata aagttcatca 11100
tgagtttcag gtatgtgaga gttatattta attctttctg ttagaggcaa aatgtctatt 11160
ttaattgcct gagcattttt ctaaaattgt tggtgacgtt tttattttct tttcctttgg 11220
catgattatt aagaacaata cacacacata caaacaagcc atttctacac attgttttca 11280
ttatttaaat ttcatggtaa attgagatct gaaagaaaaa tattatatga aagttcggac 11340
ttccatcctt gtggacagtg ctacactggc acagctagat cctcacattg ctaactccca 11400
caaaaacagt aacttctatg agcactgctt tttttttttt tttttttttt tttgagatag 11460
agttttgctc ttgttgccca ggctggactg caatggcatg atctcagctc actgcaacct 11520
tcacctcctg ggttcaagca attctcctgc ctcagccttt caggtagctg ggattacagg 11580
catgcgtcac cacgcgtggc taattttgta tttttagtag agacaggatt tcactatgtt 11640
ggtcaggctg gtctcgaact cctgacctca ggtgatccac ccgccttgga ctcgcaaagt 11700
gctgggatta caggcgtgag ccaccatgcc cggccaatta gaattgcttt gatgtagctt 11760
tgtcaactgg ttatgtgagt atgttttgca ttgaccgtga ttacatggtg tgccaaatca 11820
agcctctctt tattagaaga acaaatataa atacttaagt caaaattaga gttcaagtca 11880
attatttaat gcctttatct taaaccatca aagacagcaa gattttatat ccctagactt 11940
ttgatgtgga gtaaggtatt tttattgaga attgctagta ttatttataa gtgtatgact 12000
agataaatca tcactacata tagaatcaat ataactttgt aaaactttat gcataaatag 12060
gatatatata ttagtgaagt ctccagtgaa gcagaatcat tggggtatat atatgcagag 12120
agagatttat tttaaggaat cagctcatgc aagtgtgcgg ctgtcaagtc tgaaatctgt 12180
aaagcaggct acagactaga aatccaggta agaattgttg cagccttggg tccaaattcc 12240
atggagcagc aagttggaaa ctcaggcagg gtttcagtgt tgcagtctcg agaatccttc 12300
ttcaggaaac ctcagccttt tatcctgaag gccttcaaat gattggatga agcccaccct 12360
cattatgaag ggtaatcacc tttactcagt ctactgattt aaatgttaac aacatctaaa 12420
aaataccttc acaacaacat ctagactggt atttaatcaa acagttggat atcatagcct 12480
agccaagttg acacataaaa ttgaccatca caatagctaa gaaattaaga atttcttatc 12540
tgtttgtctt aggctccatt tggaatggaa gctgaatatg cacatccttt ggagactcta 12600
attcttggaa ctggattttt cattggaatc gtgcttttgt gtgatcatgt aattcttctt 12660
tgggcatggg tgaccattcg tttattagaa actattgatg tccataggtg agtattaatt 12720
tctgttcagg tataaagcat aatgaaatat atttattttc atggccataa gattatcata 12780
tttctaagga gactaatagg agaagttaat cttcttaatg ttatattaag aaaacataac 12840
tgttggataa aagtttaaat aatagatgtt tttacattct agcctatgct gttataattt 12900
ttatagtgat aatgtgttat tagggcaagt atatattcag gaccagcaat ttccttatcc 12960
ttctgtaata aacctaaact taactcatat ttgaaaaaaa tatcaaagca ttcagccttc 13020
cttgaataag actttctaat ctctactgtt cagcactgat aaaggcactt gcaagatgaa 13080
actactactt gtaacacata catatttcaa atgcatcctt tctgttgatt ggaagacatt 13140
ttgtggtaaa ttatttatat tgaatgcctt cttaaatgct tatcctaatt gttcattatt 13200
ttttaattat atgttcattg cattttgact tgggacatac ttctgtactc atgaatgcag 13260
aatatcaaat tctaagaatt atttttaaag tgctaaagta gcaaaattaa tgcttctagt 13320
cctaggcaga gaatattctt ctgtagaaaa attgtaattg acatttcttt cttttttttt 13380
tctatccatt gtttctttct gccttccttc ctctaagctc ctcaaaggaa gagagggtta 13440
gagtgattca aataagtata actggatgtc tgattgtaga tatgtagttg gaaataaagg 13500
agcatacttt aaatgggact cttttttgaa gccatttgtc ttctgccaac tatagaaaag 13560
tacactggta ttttgattaa ttgtggtaca tttgattcca acttgtcatt gcctaaaaaa 13620
gtaaatgaag ttgctataca gggattcatg ggcctgccct ttttaatact tgatactaat 13680
tttatgtgac ttttcctaaa aaacatattt agtattttgg gctttattta caactgttat 13740
acatgatggt gagaaagctt cctctaaaac ataaaagaaa attaattctt aaaaatctgt 13800
gtctaaagat tcattactat aatccgtctc ttccatcatt catatatttt atcataaaat 13860
aaatgatttt cttagttttt ttaaggattt tttttcttag agtggtttct agaatataca 13920
ccattttctg tgtttgctgt ttgtgaacac ttagaaataa agtggtctag gcaaagtggc 13980
atgttatcta aattggttaa tgtgaacaca tgattattaa taaaaacaac aatcatttga 14040
gatgtattta ttccttaata atctttatca tttttgtttc agtggttatg atattcctct 14100
caacccttta aatctgatcc ctttctatgc tggttctcgg catcatgatt tccaccacat 14160
gaacttcatt ggaaactatg cttcaacatt tacatggtgg gatcgaattt ttggaacaga 14220
ctctcagtat aatgcctata atgaaaagag gaagaagttt gagaaaaaga ctgaataaat 14280
atctcacgta aaccttcctg aaagataaac gttttcctga attcagaaac tagtagctaa 14340
cattgcttct ggagagcaga aataagcatg tcttctggct actaagtgat aaaaagaaca 14400
ttaacaacct ttaattacct tcctagtggg aactttttct actttaccta caagttctat 14460
atatgtagaa atgaataaat atatatttaa gtacagtttt catgaggaag ttttaaaaga 14520
ccatgttcct aagcttccaa gaaggttttg gatactagaa gtattaatct atggcttttc 14580
tcccagtaaa accataggcc tgaagttcac attgggtctt taaatctttt agatatatac 14640
tggtcatttc agaaaattct tcatagtggt attggcctta tatttaactt tttttttatt 14700
ttttttttga gacaaagcca cactctgtct ccttggctgg agtgtggtgg cacagtctca 14760
gctcactgca acctctgcct cccagttcaa gcaattcttc tgcctcagcc tcccaagtag 14820
ctgggattac aggcacccgc caccacgccc agctaatttt tgtatttttg tagagatggg 14880
gtttcacgat gttggccagg ctggtctcaa acttctgacc tcaagtgatc tgcccacctt 14940
ggcctcccaa agtgctggga ttacaggtgt aagccactgc gcccggcctt tttaacttta 15000
aacatgtttt agaattcacc taaagatcaa aatatcatgg attgaacctc atcaattgat 15060
agcagtgagt gactgaagct tccaaatcaa gaaaagccgg caccaagaac ttccattcta 15120
atctagagct gaccagtttg agctgattct ctctttgaag agtccttctt gattgcagtg 15180
cagtactggc atttctgaat ggatgtaagt ggagtatttt agtctaaagg cttttcaaat 15240
tacttgaatt tttttaaaaa ttgaggagct ttatttctat ttacccttcc atttttgtat 15300
atcaaatttc cattgtcatt aaaaactgta tcttgaaact ttgtgaactg acttgctgta 15360
tttgcacttt gagctcttga aataaatgtg atttttgtgt gattatctgg tttccagttt 15420
taaacattaa ctgtcacctt ttattcttaa acttgaaagt acagaaatca ttaaattatt 15480
aagttgtaca ataaaa 15496
Claims (11)
1.一种化妆用护肤组合物,包含:
a)棕榈酰二肽-7(pal-KT)和乙酰基四肽-11(ac-PPYL)[SEQ ID NO:1]的组合;以及
b)皮肤病学可接受的载体。
2.根据权利要求1所述的组合物,其中所述pal-KT以0.00005%至5%存在。
3.根据权利要求1或2所述的组合物,其中所述ac-PPYL[SEQ ID NO:1]以0.00005%至5%存在。
4.根据任一前述权利要求所述的组合物,其中所述pal-KT和ac-PPYL[SEQ ID NO:1]以10:1至1:10的比率存在。
5.根据任一前述权利要求所述的组合物,还包含至少一种附加成分,所述至少一种附加成分选自维生素、矿物质、肽、糖胺、防晒剂、控油剂、类黄酮化合物、抗氧化剂、蛋白酶抑制剂、酪氨酸酶抑制剂、抗炎剂、保湿剂、剥落剂、亮肤剂、抗痤疮剂、抗皱剂、植物甾醇、N-酰基氨基酸化合物、抗微生物剂、抗真菌剂、pH调节剂、增稠剂、防腐剂以及它们的组合。
6.根据权利要求5所述的组合物,其中所述附加成分包括维生素B3化合物、维生素A化合物、维生素E化合物、糖类或植物提取物。
7.根据权利要求5所述的组合物,还包含0.1%至5%的流变改性剂。
8.根据权利要求7所述的组合物,其中所述组合物是水与油的重量比为12:1至1:1的水包油,并且所述流变改性剂包含超吸收聚合物增稠剂。
9.一种处理皮肤的非治疗性方法,包括:
a)识别期望处理的目标皮肤部分;以及
b)在处理期的过程内向所述目标皮肤部分施用根据任一前述权利要求所述的护肤组合物。
10.根据权利要求7所述的方法,其中所述处理期为至少2周,优选4周。
11.根据权利要求7或8所述的方法,其中所述方法改善可见的皮肤老化迹象。
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PCT/US2022/070278 WO2022159968A1 (en) | 2021-01-22 | 2022-01-21 | Skin care composition comprising a combination of peptides |
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