CN109477089A - 新型基因重组牛痘病毒 - Google Patents

新型基因重组牛痘病毒 Download PDF

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CN109477089A
CN109477089A CN201780033837.8A CN201780033837A CN109477089A CN 109477089 A CN109477089 A CN 109477089A CN 201780033837 A CN201780033837 A CN 201780033837A CN 109477089 A CN109477089 A CN 109477089A
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cancer
vaccinia virus
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中尾慎典
川濑龙也
中村贵史
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Abstract

本发明提供对于癌症的预防或治疗有效的基因重组牛痘病毒。具体而言，本发明提供包含编码IL‑7的多核苷酸和编码IL‑12的多核苷酸这两种多核苷酸的牛痘病毒、含有包含编码IL‑7的多核苷酸的牛痘病毒和包含编码IL‑12的多核苷酸的牛痘病毒这两种牛痘病毒的组合试剂盒、以及上述两种牛痘病毒的组合使用。

Description

新型基因重组牛痘病毒
技术领域
本发明涉及新型基因重组牛痘病毒。
背景技术
近年来，已开发出将病毒用于癌症治疗的各种技术，作为癌症治疗中使用的病毒之一，有牛痘病毒。对于牛痘病毒，作为将治疗用基因送向癌细胞的载体、作为在癌细胞中增殖并破坏癌细胞的肿瘤溶解性病毒、或者作为表达癌抗原或免疫调节分子的癌疫苗，以癌症治疗为目的进行了研究(Expert Opinion on Biological Therapy,2011,Vol.11,p.595-608)。
据报道，按照通过编码白细胞介素-12(IL-12)或白细胞介素-21(IL-21)的外源基因的插入使N1L基因失活、并且通过LacZ报告基因和萤火虫荧光素酶基因的插入使胸苷激酶(TK)基因发生缺陷的方式进行操作而得到的牛痘病毒在荷瘤小鼠中带来肿瘤生长的抑制或存活率的改善(专利文献1)。
关于使作为病毒蛋白的牛痘病毒生长因子(VGF)和O1L的功能缺陷、在癌细胞内特异性增殖而破坏癌细胞的重组牛痘病毒，报道了要将其用于癌症治疗的技术。还说明了在该病毒中可以将标记基因、编码具有细胞毒性或免疫激活效果的产物的治疗用基因等外源基因导入到非牛痘病毒的生命周期所必须的基因中，在实施例中具体验证的是作为标记基因的荧光素酶-绿色荧光蛋白(GFP)融合基因或DsRed表达盒的导入。未验证治疗用基因的导入。也没有关于将多个治疗用基因组合的启示(专利文献2)。
另一方面，在使用重组蛋白的研究中，有如下报道：作为对单离的CD8+T细胞的作用，单独的人重组白细胞介素-7(IL-7)蛋白对CD8+T细胞不会诱发可检测水平的干扰素-γ(IFN-γ)产生，但人重组IL-7蛋白与人重组IL-12蛋白的组合协同地促进该IFN-γ产生(The Journal of Immunology,1995,Vol.154,p.5093-5102)。关于表达免疫刺激分子的肿瘤溶解性牛痘病毒，报道了有可能通过强免疫应答早期地清除病毒。还说明了强免疫应答对于牛痘病毒介导的癌症治疗法而言亦敌亦友(Molecular Therapy,2005,Vol.11,No.2,p.180-195)。
现有技术文献
专利文献
专利文献1：国际公开第2015/150809号
专利文献2：国际公开第2015/076422号
发明内容
发明所要解决的问题
本发明的课题在于提供用于治疗或预防癌症的基因重组牛痘病毒(特别是肿瘤溶解性的牛痘病毒)、药物组合物和组合试剂盒。
用于解决问题的方法
本发明人在牛痘病毒的制作中反复进行了大量的创见研究，结果，制作了包含编码IL-7的多核苷酸的牛痘病毒或包含编码IL-12的多核苷酸的牛痘病毒、以及包含编码IL-7的多核苷酸和编码IL-12的多核苷酸这两种多核苷酸的牛痘病毒(实施例2)，并发现1)包含编码IL-7的多核苷酸和编码IL-12的多核苷酸这两种多核苷酸的牛痘病毒、以及2)包含编码IL-7的多核苷酸的牛痘病毒与包含编码IL-12的多核苷酸的牛痘病毒这两种牛痘病毒的混合物对各种人癌细胞显示出细胞溶解作用(实施例3)，从而完成了本发明。
1)包含编码IL-7的多核苷酸和编码IL-12的多核苷酸这两种多核苷酸的牛痘病毒在荷瘤人源化小鼠模型中显示出肿瘤缩减作用(实施例6)，在同系荷瘤小鼠模型中显示出完全缓解(实施例7)，进而诱导获得性免疫而持续得到抗肿瘤效果(实施例8)。另外，2)包含编码IL-7的多核苷酸的牛痘病毒与包含编码IL-12的多核苷酸的牛痘病毒这两种牛痘病毒的混合物在同系荷瘤小鼠模型中显示出完全缓解(实施例7)，进而诱导获得性免疫而持续得到抗肿瘤效果(实施例8)。
即，本发明可以包含作为医学上或产业上有用的物质或方法的下述发明。
[1]一种牛痘病毒，其包含下述(1)和(2)：
(1)编码白细胞介素-7(IL-7)的多核苷酸；和
(2)编码白细胞介素-12(IL-12)的多核苷酸。
[2]一种药物组合物，其选自下述(1)或(2)：
(1)用于与含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物组合使用的、含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物；或者
(2)用于与含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物组合使用的、含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物。
[3]一种组合试剂盒，其含有下述(1)和(2)的牛痘病毒：
(1)包含编码IL-7的多核苷酸的牛痘病毒；和
(2)包含编码IL-12的多核苷酸的牛痘病毒。
[4]如[1]所述的牛痘病毒，其牛痘病毒生长因子(VGF)的功能发生了缺陷。
[5]如[1]所述的牛痘病毒，其O1L的功能发生了缺陷。
[6]如[1]所述的牛痘病毒，其VGF和O1L的功能发生了缺陷。
[7]如[1]所述的牛痘病毒，其缺失B5R胞外区的SCR(短共有重复序列，shortconsensus repeat)结构域。
[8]如[1]所述的牛痘病毒，其VGF和O1L的功能发生了缺陷，并且缺失B5R胞外区的SCR结构域。
[9]如[1]和[4]～[8]中任一项所述的牛痘病毒，其为LC16mO株。
[10]一种药物组合物，其包含[1]和[4]～[9]中任一项所述的牛痘病毒和药学上可接受的赋形剂。
[11]如[2]所述的药物组合物或[3]所述的试剂盒，其中，牛痘病毒的VGF的功能发生了缺陷。
[12]如[2]所述的药物组合物或[3]所述的试剂盒，其中，牛痘病毒的O1L的功能发生了缺陷。
[13]如[2]所述的药物组合物或[3]所述的试剂盒，其中，牛痘病毒的VGF和O1L的功能发生了缺陷。
[14]如[2]所述的药物组合物或[3]所述的试剂盒，其中，牛痘病毒缺失B5R胞外区的SCR结构域。
[15]如[2]所述的药物组合物或[3]所述的试剂盒，其中，牛痘病毒的VGF和O1L的功能发生了缺陷，并且缺失B5R胞外区的SCR结构域。
[16]如[2]和[11]～[15]中任一项所述的药物组合物或[3]和[11]～[15]中任一项所述的试剂盒，其中，牛痘病毒为LC16mO株。
[17]如[2]和[11]～[16]中任一项所述的药物组合物或[3]和[11]～[16]中任一项所述的试剂盒，其中，包含药学上可接受的赋形剂。
[18]如[10]～[17]中任一项所述的药物组合物或试剂盒，其用于癌症的预防或治疗。
[19]如[18]所述的药物组合物或试剂盒，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
[20]一种预防或治疗癌症的方法，其包括对需要癌症的预防或治疗的对象施用[1]和[4]～[9]中任一项所述的牛痘病毒的步骤。
[21]如[20]所述的方法，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
[22]如[1]和[4]～[9]中任一项所述的牛痘病毒，其用于在癌症的预防或治疗中使用。
[23]如[22]所述的牛痘病毒，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
[24][1]和[4]～[9]中任一项所述的牛痘病毒在制造癌症的预防或治疗用药物组合物中的应用。
[25]如[24]所述的应用，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
[26]一种预防或治疗癌症的方法，其包括：对需要癌症的预防或治疗的对象施用(1)包含编码IL-7的多核苷酸的牛痘病毒和(2)包含编码IL-12的多核苷酸的牛痘病毒的步骤。
[27]如[26]所述的方法，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
[28]一种牛痘病毒，其选自下述(1)或(2)：
(1)用于与含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物组合使用而在癌症的预防或治疗中使用的、包含编码IL-7的多核苷酸的牛痘病毒；或者
(2)用于与含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物组合使用而在癌症的预防或治疗中使用的、包含编码IL-12的多核苷酸的牛痘病毒。
[29]如[28]所述的牛痘病毒，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
[30]一种牛痘病毒的应用，其选自下述(1)或(2)：
(1)包含编码IL-7的多核苷酸的牛痘病毒在制造与含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物组合使用的癌症的预防或治疗用药物组合物中的应用；或者
(2)包含编码IL-12的多核苷酸的牛痘病毒在制造与含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物组合使用的癌症的预防或治疗用药物组合物中的应用。
[31]如[30]所述的应用，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
[32](1)包含编码IL-7的多核苷酸的牛痘病毒和(2)包含编码IL-12的多核苷酸的牛痘病毒在制造用于癌症的预防或治疗的组合试剂盒中的应用。
[33]如[32]所述的应用，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
发明效果
本发明的牛痘病毒、以及本发明的药物组合物和组合试剂盒中含有的牛痘病毒显示出肿瘤溶解作用，在癌细胞中使搭载于病毒中的多核苷酸所编码的IL-12多肽和IL-7多肽表达，带来完全缓解和获得性免疫，本发明的牛痘病毒、药物组合物和组合试剂盒能够用于癌症的预防或治疗。
附图说明
图1示出本发明中使用的转移载体质粒DNA的一例。图1上示出将以能够工作的方式与启动子连接的BFP基因并入到VGF基因内的例子。图1下示出将以能够工作的方式与启动子连接的BFP基因并入到O1L基因内的例子。
图2示出各种重组牛痘病毒(LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-LacZ和在该病毒载体制作的过程中构建的各种病毒)的基因组结构的示意图。
图3示出各种重组牛痘病毒(LC16mO ΔSCR VGF-SP-IL12/O1L-SP-LacZ、LC16mOΔSCR VGF-SP-IL7/O1L-SP-LacZ)的基因组结构的示意图。
图4示出重组牛痘病毒(LC16mO ΔSCR VGF-SP-IL12/O1L-SP-IL7)的基因组结构的示意图。
图5-1示出重组牛痘病毒(LC16mO ΔSCR VGF-SP-IL12/O1L-SP-IL7)的肿瘤溶解性。纵轴表示癌细胞存活率(％)。误差棒表示标准偏差。
图5-2示出重组牛痘病毒(LC16mO ΔSCR VGF-SP-IL12/O1L-SP-IL7)的肿瘤溶解性。纵轴表示癌细胞存活率(％)。误差棒表示标准偏差。图5-1和图5-2是除了所测定的细胞种类不同以外在相同的实验条件下得到的图。
图5-3示出两种重组牛痘病毒的混合物(LC16mO ΔSCR VGF-SP-IL12/O1L-SP-LacZ与LC16mO ΔSCR VGF-SP-IL7/O1L-SP-LacZ的混合物)的肿瘤溶解性。纵轴表示癌细胞存活率(％)。误差棒表示标准偏差。
图5-4示出两种重组牛痘病毒的混合物(LC16mO ΔSCR VGF-SP-IL12/O1L-SP-LacZ与LC16mO ΔSCR VGF-SP-IL7/O1L-SP-LacZ的混合物)的肿瘤溶解性。纵轴表示癌细胞存活率(％)。误差棒表示标准偏差。图5-3和图5-4是除了所测定的细胞种类不同以外在相同的实验条件下得到的图。
具体实施方式
以下，对本发明进行详细说明。
<本发明的牛痘病毒、用于组合使用的药物组合物和组合试剂盒>
本发明提供一种牛痘病毒，其包含下述(1)和(2)：
(1)编码IL-7的多核苷酸；和
(2)编码IL-12的多核苷酸。
(本说明书中，将该牛痘病毒也称为“本发明的牛痘病毒”)
另外，本发明提供一种药物组合物，其选自下述(1)或(2)：
(1)用于与含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物组合使用的、含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物；或者
(2)用于与含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物组合使用的、含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物。
(本说明书中，将该药物组合物也称为“本发明的用于组合使用的药物组合物”，将上述(1)或(2)所述的本发明的用于组合使用的药物组合物中分别含有的包含编码IL-7的多核苷酸的牛痘病毒或包含编码IL-12的多核苷酸的牛痘病毒也称为“用于组合使用的牛痘病毒”)
另外，本发明提供一种组合试剂盒，其含有下述(1)和(2)的牛痘病毒：
(1)包含编码IL-7的多核苷酸的牛痘病毒；和
(2)包含编码IL-12的多核苷酸的牛痘病毒。
(本说明书中，将该组合试剂盒也称为“本发明的组合试剂盒”，将本发明的组合试剂盒中含有的各牛痘病毒也称为“组合试剂盒用牛痘病毒”)
本发明的组合试剂盒是指为了施用(1)包含编码IL-7的多核苷酸的牛痘病毒和(2)包含编码IL-12的多核苷酸的牛痘病毒这两种牛痘病毒而使用的一种或多种药物组合物。在同时施用两种牛痘病毒的情况下，组合试剂盒可以将上述两种组合试剂盒用牛痘病毒一起含有在粉末剂这样的单一的药物组合物中、或者分别含有在多个药物组合物中。因此，本发明的组合试剂盒包含下述药物组合物，该药物组合物含有包含编码IL-7的多核苷酸的牛痘病毒和包含编码IL-12的多核苷酸的牛痘病毒这两种牛痘病毒。在不同时施用两种组合试剂盒用牛痘病毒的情况下，组合试剂盒在单独的药物组合物中分别含有上述两种组合试剂盒用牛痘病毒。例如，组合试剂盒在单一包装中的单独的药物组合物中、或者在单独的包装中的单独的药物组合物中含有上述两种组合试剂盒用牛痘病毒。本发明的组合试剂盒可以含有药学上可接受的赋形剂。
本发明的牛痘病毒、用于组合使用的牛痘病毒、以及组合试剂盒用牛痘病毒中使用的牛痘病毒是属于痘病毒科正痘病毒属的病毒。本发明中使用的牛痘病毒株没有限定，可以列举例如Lister株、纽约市卫生委员会(New York City Board of Health)(NYBH)株、Wyeth株、哥本哈根株、Western Reserve(WR)株、改良型牛痘病毒安卡拉(ModifiedVaccinia Ankara，MVA)株、EM63株、池田株、大连株、Tian Tan株等，Lister株、MVA株可由美国典型培养物保藏中心获得(分别为ATCC VR-1549和ATCC VR-1508)。此外，作为本发明中使用的牛痘病毒，也可以使用以这些株作为来源而建立的牛痘病毒株。例如，作为本发明中使用的牛痘病毒，也可以使用由Lister株建立的LC16株、LC16m8株和LC16mO株。LC16mO株是将Lister株作为亲本株进行低温传代、经由LC16株而制作出的株。LC16m8株是将LC16mO株进一步低温传代而制作出的株，该株在作为编码病毒膜蛋白的基因的B5R基因中确认到移码突变，该蛋白质不再表达和发挥功能，由此进行了减毒化(蛋白质核酸酶,2003,Vol.48,p.1693-1700)。作为Lister株、LC16m8株和LC16mO株的全基因组序列，例如分别已知有登录号AY678276.1、登录号AY678275.1和登录号AY678277.1。因此，可以由Lister株利用公知的同源重组或定点诱变法制作LC16m8株和LC16mO株。
在一个实施方式中，本发明中使用的牛痘病毒为LC16mO株。
作为本发明中使用的牛痘病毒，可以使用减毒化和/或肿瘤选择性牛痘病毒。在本说明书中，“减毒化”是指对正常细胞(例如非肿瘤细胞)的毒性(例如细胞溶解性)低。在本说明书中，“肿瘤选择性”是指与正常细胞(例如非肿瘤细胞)相比对肿瘤细胞的毒性(例如肿瘤溶解性)高。作为本发明中使用的牛痘病毒，可以使用施加了使特定蛋白的功能缺陷、或者抑制特定基因或蛋白的表达这样的基因改变的牛痘病毒(Expert Opinion onBiological Therapy,2011,Vol.11,p.595-608)。例如，为了提高牛痘病毒的肿瘤选择性，可以使用使TK的功能缺陷的牛痘病毒(Cancer Gene Therapy,1999,Vol.6,p.409-422)、使VGF的功能缺陷的牛痘病毒(Cancer Research,2001,Vol.61,p.8751-8757)、包含修饰TK基因和修饰血凝素(HA)基因以及修饰F3基因或中断的F3基因座的牛痘病毒(国际公开第2005/047458号)、使VGF和O1L的功能缺陷的牛痘病毒(国际公开第2015/076422号)、在B5R基因的3’非翻译区内插入有在癌细胞中表达降低的小分子RNA的靶序列的牛痘病毒(国际公开第2011/125469号)、使VGF和TK的功能缺陷的牛痘病毒(Cancer Research,2001,Vol.61,p.8751-8757)、使TK和HA以及F14.5L的功能缺陷的牛痘病毒(Cancer Research,2007,Vol.67,p.10038-10046)、使TK和B18R的功能缺陷的牛痘病毒(PLoS Medicine,2007,Vol.4,p.e353)、使TK和核糖核苷酸还原酶的功能缺陷的牛痘病毒(PLoS Pathogens,2010,Vol.6,p.e1000984)、使SPI-1和SPI-2的功能缺陷的牛痘病毒(Cancer Research,2005,Vol.65,p.9991-9998)、使SPI-1、SPI-2和TK的功能缺陷的牛痘病毒(Gene Therapy,2007,Vol.14,p.638-647)、或者在E3L和K3L区域具有突变的牛痘病毒(国际公开第2005/007824号)。另外，可以使用使O1L的功能缺陷的牛痘病毒(Journal of Virology,2012,Vol.86,p.2323-2336)。另外，期待在生物体内减弱因抗牛痘病毒抗体的中和效果所致的病毒的排除，可以使用使B5R的胞外区缺陷的牛痘病毒(Virology,2004,Vol.325,p.425-431)或者使A34R区域缺陷的牛痘病毒(Molecular Therapy,2013,Vol.21,p.1024-1033)。另外，期待由牛痘病毒产生的免疫细胞活化作用，可以使用使白细胞介素-1b(IL-1b)受体缺陷的牛痘病毒(国际公开第2005/030971号)。这些外源基因的插入或基因的缺失、突变可以利用例如公知的同源重组或定点诱变法来进行。另外，在本发明中，作为牛痘病毒，可以使用具有这些基因改变的组合的牛痘病毒。在本说明书中，“缺陷”是指由该术语特别限定的基因区域不具有功能，以包括缺失了由该术语特别限定的基因区域的含义使用。例如，“缺陷”可以是在由特别限定的基因区域构成的区域中发生了缺失，也可以是在包含特别限定的基因区域的周围的基因区域发生了缺失。
在一个实施方式中，本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒的VGF的功能发生了缺陷。在一个实施方式中，本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒的O1L的功能发生了缺陷。在一个实施方式中，本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒的VGF和O1L的功能发生了缺陷。可以基于国际公开第2015/076422号中记载的方法使牛痘病毒发生VGF和/或O1L的功能缺陷。
VGF是与表皮生长因子(EGF)具有高度的氨基酸序列同源性的蛋白质，与EGF同样地与表皮生长因子受体结合，引起Ras、Raf、丝裂原活化蛋白激酶(Mitogen-activatedprotein kinase、MAPK)/细胞外信号调节激酶(the extracellular signal-regulatedkinase、ERK)激酶(MAPK/ERK激酶、MEK)、以及与ERK相连的信号级联的活化，促进细胞分裂。
O1L维持ERK的活化，与VGF一同有助于细胞的分裂。
牛痘病毒的VGF和/或O1L的功能的缺陷是指，不表达编码VGF的基因和/或编码O1L的基因；或者即使表达，其表达蛋白质也不保持VGF和/或O1L的正常功能。为了使牛痘病毒的VGF和/或O1L的功能缺陷，使编码VGF的基因和/或编码O1L的基因全部或部分缺失即可。另外，也可以通过碱基的置换、缺失、插入或添加使基因发生突变，以使其无法表达正常的VGF和/或O1L。另外，也可以在编码VGF的基因和/或编码O1L的基因中插入外源基因。本发明中，在因基因的置换、缺失、插入或添加等突变而不表达正常的基因产物的情况下，称为基因缺陷。
关于本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒的VGF和/或O1L的功能是否发生了缺陷，可以使用公知的方法来判断。例如可以通过下述方法来判断：进行VGF和/或O1L的功能评价；利用使用抗VGF的抗体或抗O1L的抗体的免疫化学方法来确认VGF或O1L的存在；利用聚合酶链式反应(PCR)来确定编码VGF的基因或编码O1L的基因的存在。
B5R(登录号AAA48316.1)是存在于牛痘病毒的包膜上的I型膜蛋白，当病毒感染、传播到相邻的细胞或宿主体内的其他部位时，其发挥提高感染效率的作用。在B5R的胞外区存在4个称为SCR结构域的结构(Journal of Virology,1998,Vol.72,p.294-302)。在一个实施方式中，本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒缺失了B5R的胞外区的SCR结构域。
牛痘病毒的B5R胞外区的SCR结构域的缺失包括B5R胞外区的4个SCR结构域的一部分或全部的缺失，是指编码B5R胞外区内的4个SCR结构域的一部分或全部的基因区域不进行表达，或者所表达的B5R蛋白未保持胞外区的4个SCR结构域中的一部分或全部。在一个实施方式中，在本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒中，B5R的4个SCR结构域全部缺失。在一个实施方式中，在本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒中缺失的4个SCR结构域为上述登录号AAA48316.1的氨基酸序列中第22位的氨基酸至第237位的氨基酸所对应的区域。
关于本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒是否缺失B5R胞外区的SCR结构域，可以使用公知的方法来判断。例如可以通过下述方法来判断：利用使用针对SCR结构域的抗体的免疫化学方法来确认SCR结构域的存在；利用PCR来确定编码SCR结构域的基因的存在或大小。
在一个实施方式中，本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒为VGF和O1L的功能发生了缺陷、并且缺失B5R胞外区的SCR结构域的牛痘病毒。
在一个实施方式中，本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒为VGF和O1L的功能发生了缺陷、并且缺失B5R胞外区的SCR结构域的LC16mO株牛痘病毒。
在一个实施方式中，本发明的牛痘病毒为包含编码IL-7的多核苷酸和编码IL-12的多核苷酸、VGF和O1L的功能发生了缺陷的牛痘病毒。
在一个实施方式中，本发明的牛痘病毒为包含编码IL-7的多核苷酸和编码IL-12的多核苷酸、VGF和O1L的功能发生了缺陷的LC16mO株牛痘病毒。
在一个实施方式中，本发明的牛痘病毒为包含编码IL-7的多核苷酸和编码IL-12的多核苷酸、VGF和O1L的功能发生了缺陷、并且缺失B5R胞外区的SCR结构域的牛痘病毒。
在一个实施方式中，本发明的牛痘病毒为包含编码IL-7的多核苷酸和编码IL-12的多核苷酸、VGF和O1L的功能发生了缺陷、并且缺失B5R胞外区的SCR结构域的LC16mO株牛痘病毒。
在一个实施方式中，用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒为包含编码IL-7的多核苷酸、VGF和O1L的功能发生了缺陷的牛痘病毒，或者为包含编码IL-12的多核苷酸、VGF和O1L的功能发生了缺陷的牛痘病毒。
在一个实施方式中，用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒为包含编码IL-7的多核苷酸、VGF和O1L的功能发生了缺陷的LC16mO株牛痘病毒，或者为包含编码IL-12的多核苷酸、VGF和O1L的功能发生了缺陷的LC16mO株牛痘病毒。
在一个实施方式中，用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒为包含编码IL-7的多核苷酸、VGF和O1L的功能发生了缺陷、并且缺失B5R胞外区的SCR结构域的牛痘病毒，或者为包含IL-12的多核苷酸、VGF和O1L的功能发生了缺陷、并且缺失B5R胞外区的SCR结构域的牛痘病毒。
在一个实施方式中，用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒为包含编码IL-7的多核苷酸、VGF和O1L的功能发生了缺陷、并且缺失B5R胞外区的SCR结构域的LC16mO株牛痘病毒，或者为包含编码IL-12的多核苷酸、VGF和O1L的功能发生了缺陷、并且缺失B5R胞外区的SCR结构域的LC16mO株牛痘病毒。
IL-7是作为激动剂对IL-7受体发挥功能的分泌性蛋白质。据报道，IL-7有助于T细胞、B细胞等的存活、增殖和分化(Current Drug Targets,2006,Vol.7,p.1571-1582)。本发明中，IL-7包含天然存在的IL-7和具有其功能的变体。在一个实施方式中，IL-7为人IL-7。本发明中，人IL-7包含天然存在的人IL-7和具有其功能的变体。在一个实施方式中，人IL-7选自由下述(1)～(3)组成的组：
(1)包含登录号NP_000871.1所示的氨基酸序列、并且具有人IL-7的功能的多肽、
(2)由在登录号NP_000871.1所示的氨基酸序列中缺失、置换、插入和/或添加1～10个氨基酸而得到的氨基酸序列构成、并且具有人IL-7的功能的多肽、以及
(3)包含与登录号NP_000871.1所示的氨基酸序列的一致性为90％以上的氨基酸序列、并且具有人IL-7的功能的多肽。
在此，人IL-7的功能是指对人免疫细胞的各种存活、增殖和分化作用。
优选本发明中使用的人IL-7为由登录号NP_000871.1所示的氨基酸序列构成的多肽。
IL-12为IL-12亚基p40与IL-12亚基α的杂二聚体。据报道，IL-12具有活化并分化诱导T细胞和NK细胞的功能(Cancer Immunology Immunotherapy,2014,Vol.63,p.419-435)。本发明中，IL-12包含天然存在的IL-12和具有其功能的变体。在一个实施方式中，IL-12为人IL-12。本发明中，人IL-12包含天然存在的人IL-12和具有其功能的变体。在一个实施方式中，人IL-12选自由作为人IL-12亚基p40与人IL-12亚基α的组合的下述(1)～(3)组成的组：
(1)包含(1-a)登录号NP_002178.2所示的氨基酸序列的多肽、(1-b)由在登录号NP_002178.2所示的氨基酸序列中缺失、置换、插入和/或添加1～10个氨基酸而得到的氨基酸序列构成的多肽、或者(1-c)包含与登录号NP_002178.2所示的氨基酸序列的一致性为90％以上的氨基酸序列的多肽、以及
(2-a)包含登录号NP_000873.2所示的氨基酸序列的多肽、(2-b)由在登录号NP_000873.2所示的氨基酸序列中缺失、置换、插入和/或添加1～10个氨基酸而得到的氨基酸序列构成的多肽、或者(2-c)包含与登录号NP_000873.2所示的氨基酸序列的一致性为90％以上的氨基酸序列的多肽、
并且具有人IL-12的功能的多肽；
(2)包含(1-a)由登录号NP_002178.2所示的氨基酸序列构成的多肽、以及
(2-a)包含登录号NP_000873.2所示的氨基酸序列的多肽、(2-b)由在登录号NP_000873.2所示的氨基酸序列中缺失、置换、插入和/或添加1～10个氨基酸而得到的氨基酸序列构成的多肽、或者(2-c)包含与登录号NP_000873.2所示的氨基酸序列的一致性为90％以上的氨基酸序列的多肽、
并且具有人IL-12的功能的多肽；以及
(3)包含(1-a)包含登录号NP_002178.2所示的氨基酸序列的多肽、(1-b)由在登录号NP_002178.2所示的氨基酸序列中缺失、置换、插入和/或添加1～10个氨基酸而得到的氨基酸序列构成的多肽、或者(1-c)包含与登录号NP_002178.2所示的氨基酸序列的一致性为90％以上的氨基酸序列的多肽、以及
(2-a)由登录号NP_000873.2所示的氨基酸序列构成的多肽、
并且具有人IL-12的功能的多肽。
在此，人IL-12的功能是指T细胞、NK细胞的活化作用和/或分化诱导作用。IL-12亚基p40和IL-12亚基α可以通过直接结合而形成IL-12。另外，可以借助接头使IL-12亚基p40和IL-12亚基α结合。
优选本发明中使用的人IL-12为包含由登录号NP_002178.2所示的氨基酸序列构成的多肽和由登录号NP_000873.2所示的氨基酸序列构成的多肽的多肽。
本说明书中的“一致性”是指通过NEEDLE程序(Journal of Molecular Biology,1970,Vol.48,p.443-453)检索使用默认参数而得到的值Identity。上述参数如下所示。
Gap penalty(空位罚分)＝10
Extend penalty(延伸罚分)＝0.5
Matrix(矩阵)＝EBLOSUM62
本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒具有肿瘤溶解活性。作为评价被测病毒是否具有肿瘤溶解活性的方法，可以列举对病毒添加所致的癌细胞存活率降低进行评价的方法。作为评价中使用的癌细胞，可以列举例如恶性黑色素瘤细胞RPMI-7951(例如ATCC HTB-66)、肺腺癌细胞HCC4006(例如ATCC CRL-2871)、肺癌细胞A549(例如ATCC CCL-185)、小细胞肺癌细胞DMS 53(例如ATCC CRL-2062)、肺鳞癌细胞NCI-H226(例如ATCC CRL-5826)、肾癌细胞Caki-1(例如ATCC HTB-46)、膀胱癌细胞647-V(例如DSMZ ACC 414)、头颈癌细胞Detroit 562(例如ATCC CCL-138)、乳腺癌细胞JIMT-1(例如DSMZ ACC 589)、乳腺癌细胞MDA-MB-231(例如ATCC HTB-26)、食道癌细胞OE33(例如ECACC96070808)、胶质母细胞瘤U-87MG(例如ECACC 89081402)、神经母细胞瘤GOTO(例如JCRB JCRB0612)、骨髓瘤RPMI 8226(例如ATCC CCL-155)、卵巢癌细胞SK-OV-3(例如ATCCHTB-77)、卵巢癌细胞OVMANA(例如JCRB JCRB1045)、大肠癌细胞RKO(例如ATCC CRL-2577)、大肠癌细胞HCT 116(例如ATCC CCL-247)、胰腺癌细胞BxPC-3(例如ATCC CRL-1687)、前列腺癌细胞LNCaP clone FGC(例如ATCC CRL-1740)、肝癌细胞JHH-4(例如JCRB JCRB0435)、间皮瘤NCI-H28(例如ATCC CRL-5820)、宫颈癌细胞SiHa(例如ATCC HTB-35)和胃癌细胞Kato III(例如RIKEN BRC RCB2088)。作为具体的评价方法，可以使用例如后述实施例3中记载的方法。
本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒产生IL-7和/或IL-12多肽。使用本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒时，通过产生IL-7和IL-12多肽，抗肿瘤效果显著提高。IL-7和IL-12的产生可以使用该领域中公知的方法来确认。例如，可以通过下述方法确认：将导入有编码IL-7和IL-12各多肽的多核苷酸的牛痘病毒与癌细胞进行培养后，测定培养上清中的IL-7和IL-12浓度；细胞的免疫染色或细胞溶解物的蛋白免疫印迹分析或者测定细胞溶解物中的IL-7和IL-12的浓度。IL-7和IL-12的各浓度例如可以分别使用Human IL-7 ELISA试剂盒(RayBiotech公司)、Human IL-12 p70 DuoSet ELISA(R&D Systems公司)来测定。作为具体评价培养上清中或细胞溶解物中的各种多肽浓度的方法，可以使用后述实施例4中记载的方法。细胞的免疫染色或细胞溶解物的蛋白免疫印迹分析可以分别使用市售的抗IL-7抗体、抗IL-12抗体来进行。
分别编码IL-7和IL-12的多核苷酸可以基于公众可利用的序列信息，利用该领域中公知的多核苷酸合成方法进行合成。另外，若先取得各多核苷酸，也可以通过使用定点诱变法(Current Protocols in Molecular Biology edition,1987,John Wiley&SonsSection 8.1-8.5)等本领域技术人员公知的方法在规定的位点导入突变来制作具有各多肽的功能的变体。
分别编码IL-7和IL-12的多核苷酸可以利用公知的同源重组或定点诱变法导入到牛痘病毒中。例如，可以制作在要导入的位点的碱基序列中导入有该多核苷酸的质粒(也称为转移载体质粒DNA)，并导入到感染了牛痘病毒的细胞中。优选作为外源基因的分别编码IL-7和IL-12的多核苷酸的导入区域为非牛痘病毒的生命周期所必需的基因区域。例如，在某一方式中，关于IL-7和/或IL-12的导入区域，在VGF功能缺陷牛痘病毒中可以设定为该VGF基因的内部，在O1L功能缺陷牛痘病毒中可以设定为该O1L基因的内部，在具有VGF功能缺陷和O1L功能缺陷这两种缺陷的牛痘病毒中可以设定为该VGF基因和该O1L基因中的任一者或两者的内部。上述中，外源基因可以按照与VGF和O1L基因的转录方向同向或反向地进行转录的方式导入。
转移载体质粒DNA向细胞中的导入方法没有特别限定，可以使用例如磷酸钙法、电穿孔法等。
在导入作为外源基因的分别编码IL-7和IL-12的多核苷酸时，可以在外源基因的上游以能够工作的方式连接适当的启动子。由此，在本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒中，外源基因可与能够在肿瘤细胞中表达的启动子连接。作为这些启动子，可以列举例如PSFJ1-10、PSFJ2-16、p7.5K启动子、p11K启动子、T7.10启动子、CPX启动子、HF启动子、H6启动子和T7杂合启动子等。
在一个实施方式中，本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒不具有药剂选择标记基因。
本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒的表达和/或增殖可以通过使牛痘病毒感染宿主细胞、并对感染的宿主细胞进行培养来进行。牛痘病毒的表达和/或增殖可以利用该领域中公知的方法进行。作为为了使本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒进行表达或增殖而使用的宿主细胞，只要是表达本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒并能够增殖的宿主细胞，则没有特别限制。作为这样的宿主细胞，可以列举例如BS-C-1、A549、RK13、HTK-143、Hep-2、MDCK、Vero、HeLa、CV-1、COS、BHK-21和原代兔肾脏细胞等动物细胞，优选可以使用BS-C-1(ATCC CCL-26)、A549(ATCC CCL-185)、CV-1(ATCC CCL-70)或RK13(ATCCCCL-37)。宿主细胞的培养条件例如适当选择温度、培养基的pH和培养时间。
生产本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒的方法中，除了包括使本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒感染宿主细胞，对感染的宿主细胞进行培养，使其表达本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒的步骤以外，还可以进一步包括对本发明的牛痘病毒、用于组合使用的牛痘病毒或组合试剂盒用牛痘病毒进行回收、优选进行纯化的步骤。作为纯化方法，可以采用使用Benzonase核酸酶的DNA消化、蔗糖梯度离心分离法、碘克沙醇密度梯度离心分离法、超滤法和渗滤法等。
<本发明的药物组合物>
本发明的药物组合物包含含有本发明的牛痘病毒和药学上可接受的赋形剂的药物组合物。本发明的药物组合物还包含本发明的用于组合使用的药物组合物。在一个实施方式中，本发明的用于组合使用的药物组合物包含药学上可接受的赋形剂。
本发明的药物组合物可以使用该领域中通常使用的赋形剂即药剂用赋形剂或药剂用载体等利用通常使用的方法来制备。作为这些药物组合物的剂型的例子，可以列举例如注射剂和点滴用剂等非口服剂，可以通过静脉内施用、皮下施用或肿瘤内施用等来施用。制剂化时，可以在药学上可接受的范围内使用与这些剂型相应的赋形剂、载体或添加剂等。
有效施用量根据患者的症状的程度、年龄、所使用的制剂的剂型或病毒的效价等而有所不同，例如，以病毒单独的有效施用量计、以组合试剂盒中的两种病毒的总有效施用量计、或者以组合施用时两种病毒的总有效施用量计，可以使用约102～约1010噬菌斑形成单位(PFU)。作为组合试剂盒中的两种病毒施用量的比率，例如可以以约1:10～约10:1、约1:5～约5:1、约1:3～约3:1、约1:2～约2:1或约1:1来使用。
<癌症的预防或治疗用途>
本发明的药物组合物能够用作癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的预防或治疗剂。
本发明中包括包含本发明的牛痘病毒或用于组合使用的牛痘病毒的药物组合物，该药物组合物为癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的预防或治疗用药物组合物。
本发明中包括包含各组合试剂盒用牛痘病毒的组合试剂盒，该组合试剂盒为癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的预防或治疗用组合试剂盒。
另外，本发明中包括预防或治疗癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的方法，该方法包括对需要癌症的预防或治疗的对象(例如患者)施用本发明的牛痘病毒的步骤。
另外，本发明中包括预防或治疗癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的方法，该方法包括对需要癌症的预防或治疗的对象(例如患者)施用下述(1)和(2)的步骤。
(1)包含编码IL-7的多核苷酸的牛痘病毒；和
(2)包含编码IL-12的多核苷酸的牛痘病毒。
该两种牛痘病毒可以同时分别连续地、或隔开间隔施用于对象。
另外，本发明中包括用于在癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的预防或治疗中使用的本发明的牛痘病毒。
另外，本发明中包括用于在癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的预防或治疗中使用的、选自下述(1)或(2)中的牛痘病毒。
(1)用于与含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物组合使用而在癌症的预防或治疗中使用的、包含编码IL-7的多核苷酸的牛痘病毒；或者
(2)用于与含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物组合使用而在癌症的预防或治疗中使用的、包含编码IL-12的多核苷酸的牛痘病毒。
此外，本发明中包括本发明的牛痘病毒在制造癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的预防或治疗用的药物组合物中的应用。
此外，本发明中包括一种牛痘病毒在制造癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的预防或治疗用的药物组合物中的应用，该应用选自下述(1)或(2)：
(1)包含编码IL-7的多核苷酸的牛痘病毒在制造与含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物组合使用的癌症的预防或治疗用药物组合物中的应用；或者
(2)包含编码IL-12的多核苷酸的牛痘病毒在制造与含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物组合使用的癌症的预防或治疗用药物组合物中的应用。
此外，本发明中包括包含编码IL-7的多核苷酸的牛痘病毒和包含编码IL-12的多核苷酸的牛痘病毒在制造癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症的预防或治疗用的组合试剂盒中的应用。
在本说明书中，“预防用”的含义与“用于在预防中使用”相同，“治疗用”的含义与“用于在治疗中使用”相同。
本发明的药物组合物或组合试剂盒可以与对癌症、例如选自由恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌和胃癌等组成的组中的癌症显示出有效性的各种治疗剂组合使用。关于该组合使用，可以同时施用，或者分别地连续或间隔所期望的时间间隔来施用。在同时施用的情况下，本发明的药物组合物也可以为配合剂，也可以分别地制剂化。
本发明的牛痘病毒、本发明的药物组合物、本发明的组合试剂盒、本发明的预防或治疗癌症的方法、或者适用本发明的应用的癌症也包括向原发灶以外的脏器、例如淋巴结、肝脏等的转移性癌症等。
关于本发明进行了全面的记述，为了得到进一步理解，在此提供用于参考的特定实施例，但这些实施例的目的在于例示，并不对本发明进行限定。
实施例
关于使用市售的试剂盒或试剂等的部分，只要没有特别声明，则按照附带的操作规程进行实验。
(实施例1：转移载体质粒DNA的构建)
如下制作为了利用同源重组法制作重组牛痘病毒而使用的转移载体质粒DNA。
(1)pTN-VGF-P-DsRed转移载体质粒DNA的构建
基于国际公开第2015/076422号，制作pUC19-VGF载体。更具体而言，为了制作pUC19-VGF载体，使用LC16mO株的基因组DNA(登录号AY678277.1)作为模板，并使用Invitrogen公司的pUC19载体(产品编码：54357)。将所制作的pUC19-VGF载体用限制酶AccI切断后，将末端平滑化。在其切断位点插入包含p7.5k启动子和DsRed片段的DNA片段(序列号22)，由此构建转移载体质粒DNA。将所构建的质粒DNA称为pTN-VGF-P-DsRed。
(2)pTN-VGF-SP-IL12和pTN-VGF-SP-IL7转移载体质粒DNA的构建
以pTagBFP-N载体(FP172、Evrogen公司)的DNA作为模板，利用两个引物(序列号1和序列号2)对BFP基因区域进行扩增。将该PCR产物用限制酶SfiI和EcoRI切断，克隆至pTK-SP-LG载体(国际公开第2015/076422号。其中，使用LC16mO株的基因组DNA(登录号AY678277.1)作为模板，并使用Invitrogen公司的pUC19载体(产品编码：54357)。另外，pVNC110-Luc/IRES/EGFP质粒使用国际公开第2011/125469号中记载的pVNC110-Luc/IRES/EGFP。)的相同的限制酶位点，构建在合成牛痘病毒启动子(Journal of VirologicalMethods,1997,Vol.66,p.135-138)下连接有BFP的pTK-SP-BFP。接着，将pTK-SP-BFP用限制酶SphI和EcoRI切断，将末端平滑化。将这样得到的DNA片段克隆至将pUC19-VGF载体用限制酶AccI切断并将末端平滑化而得到的位点，由此构建pTN-VGF-SP-BFP(图1)。接着，将编码人IL-12的多核苷酸(包含人IL-12亚基p40、内部核糖体导入位点和人IL-12亚基α的多核苷酸；序列号7)和编码人IL-7的多核苷酸(序列号8)(各多核苷酸在5’侧包含限制酶位点accggtcgccacc(序列号16)，在3’侧包含限制酶位点gctagcgaattc(序列号17))用限制酶AgeI和NheI切断。将各多核苷酸片段克隆至pTN-VGF-SP-BFP的相同的限制酶位点，由此构建转移载体质粒DNA。将所构建的质粒DNA分别称为pTN-VGF-SP-IL12和pTN-VGF-SP-IL7。
(3)pTN-O1L-SP-BFP、pTN-O1L-SP-LacZ、pTN-O1L-SP-IL12和pTN-O1L-SP-IL7转移载体质粒DNA的构建
利用与上述(2)同样的方法，将pTK-SP-BFP用限制酶SphI和EcoRI切断并将末端平滑化，将所得到的DNA片段克隆至将pUC19-O1L载体(国际公开第2015/076422号。其中，与pUC19-VGF载体制作同样地，使用LC16mO株的基因组DNA(登录号AY678277.1)作为模板，并使用Invitrogen公司的pUC19载体(产品编码：54357)。O1L基因区域插入至pUC19载体的XbaI位点。)用限制酶XbaI切断并将末端平滑化而得到的位点，由此制作转移载体质粒DNA(图1)。将所制作的质粒DNA称为pTN-O1L-SP-BFP。接着，将包含针对人进行了密码子优化的大肠杆菌LacZ基因的多核苷酸(序列号9)、编码人IL-12的多核苷酸(序列号7)和编码人IL-7的多核苷酸(序列号8)用限制酶AgeI和NheI切断。将编码LacZ、IL-12或IL-7的各多核苷酸片段克隆至pTN-O1L-SP-BFP载体的相同的限制酶位点(AgeI位点和NheI位点)，由此构建转移载体质粒DNA。将所构建的质粒DNA分别称为pTN-O1L-SP-LacZ、pTN-O1L-SP-IL12和pTN-O1L-SP-IL7。
(4)pTN-DsRed(B5R-)和pTN-B5RΔ1-4转移载体质粒DNA的构建
以pB5R(国际公开第2011/125469号。其中，使用LC16mO株的基因组DNA(登录号AY678277.1)作为模板)的DNA作为模板，利用两个引物(序列号3和序列号4)对B4R基因区域进行扩增。另外，以pDsRed-Express-N1(Clontech公司)的DNA作为模板，利用两个引物(序列号5和序列号6)对DsRed基因区域进行扩增。将前者的PCR产物用限制酶NotI和FspI切断，将后者的PCR产物用限制酶FspI和MfeI切断。将这两种DNA片段克隆至用限制酶NotI和MfeI切断的pB5R中，由此制作转移载体质粒DNA。将所制作的质粒DNA称为pTN-DsRed(B5R-)。另一方面，将pB5R用限制酶NotI和NspI切断、或者用限制酶NspI和SacI切断。将这两种DNA片段克隆至用限制酶NotI和SacI切断的pB5R中，由此构建转移载体质粒DNA。将所制作的质粒DNA称为pTN-B5RΔ1-4。pTN-B5RΔ1-4编码缺失了4个SCR结构域的B5R蛋白。该氨基酸序列为序列号18所示的序列。
(实施例2：基因重组牛痘病毒的构建)
由牛痘病毒LC16mO株制作使VGF和O1L的功能缺陷的重组牛痘病毒(称为LC16mOVGF-SP-LucGFP/O1L-p7.5-DsRed)。对于该病毒，使用二代测序仪PacBio RSII(PacificBioscience公司)进行测序，由所得到的序列信息利用Sprai[BMC GENOMICS.2014 AUG 21；15:699.]软件进行病毒基因组的重构来确定碱基序列，结果其具有序列号21所表示的碱基序列。另外，在该碱基序列的两末端添加有环序列，两末端环序列为序列号19或20所表示的碱基序列。
(1)回收具有图2所示的病毒基因组的重组牛痘病毒。以下，对回收步骤进行具体说明。使LC16mO VGF-SP-LucGFP/O1L-p7.5-DsRed以MOI(感染复数，Multiplicity ofinfection)＝0.02～0.1感染在6孔培养皿中培养至80％融合的CV1细胞(ATCC CCL-70)或RK13细胞(ATCC CCL-37)，在室温下使细胞贴壁1小时。将实施例1(3)中构建的pTN-O1L-SP-BFP与FuGENE(注册商标)HD转染试剂(Roche)混合，按照手册添加至细胞中使细胞进行摄取，在5％CO2存在下在37℃下培养2～5天。将细胞冻融后，进行超声波处理，利用Opti-MEM(Invitrogen)稀释至通过下述操作能够取得单个的噬菌斑的程度。将所得到的稀释液100μL添加、接种至在6孔培养皿中达到亚融合的BS-C-1细胞(ATCC CCL-26)或RK13细胞中。添加含有0.8％甲基纤维素(和光纯药、136-02155)、5％胎牛血清、0.225％碳酸氢钠(和光纯药、195-16411)和GlutaMAX(TM)Supplement I(GIBCO、35050-061)的伊格尔MEM培养基(日水、05900)2mL，在5％CO2存在下在37℃下培养2～5天。除去培养基，以BFP表达为指标用枪头尖刮取噬菌斑，悬浮于Opti-MEM中。利用BS-C-1细胞或RK13细胞进一步重复3次以上该操作，进行噬菌斑纯化，回收病毒噬菌斑(本实施例中，以下将到此为止的步骤称为“回收”)。使所回收的噬菌斑悬浮于Opti-MEM中，施加超声波。使用高纯度病毒核酸试剂盒(Roche)，按照手册从上述超声波溶液200μL中提取基因组DNA，供于通过PCR进行的筛选。关于VGF，利用两个引物(序列号10和序列号11)进行PCR，关于O1L，利用两个引物(序列号12和序列号13)进行PCR，关于B5R，利用两个引物(序列号14和序列号15)进行PCR。在检测到规定大小的PCR产物的克隆中选择出通过直接测序确认到PCR产物的碱基序列正确的病毒克隆(称为LC16mOVGF-SP-LucGFP/O1L-SP-BFP；图2)，使其在A549细胞(ATCC CCL-185)或RK13细胞中增殖后，利用RK13细胞测定病毒效价。使用LC16mO VGF-SP-LucGFP/O1L-SP-BFP和实施例1(4)中制作的pTN-DsRed(B5R-)，代替BFP表达以DsRed表达作为指标，利用与上述同样的方法回收重组病毒。将所回收的病毒称为LC16mOΔ-DsRed VGF-SP-LucGFP/O1L-SP-BFP(图2)。
(2)回收缺失了B5R蛋白的4个SCR结构域的重组病毒。具体而言，使用实施例2(1)中制作的LC16mO Δ-DsRed VGF-SP-LucGFP/O1L-SP-BFP和实施例1(4)中构建的pTN-B5RΔ1-4，代替BFP表达以DsRed表达消失作为指标，利用与实施例2(1)同样的方法回收重组病毒。将所回收的病毒称为LC16mO ΔSCR VGF-SP-LucGFP/O1L-SP-BFP(图2)。另外，使用所制作的LC16mO ΔSCR VGF-SP-LucGFP/O1L-SP-BFP和实施例1(1)中构建的pTN-VGF-P-DsRed，代替BFP表达以DsRed表达作为指标，利用与实施例2(1)同样的方法回收重组病毒。将所回收的病毒称为LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-BFP(图2)。接着，使用所制作的LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-BFP和实施例1(3)中构建的pTN-O1L-SP-LacZ，代替BFP表达以BFP表达消失作为指标，利用与实施例2(1)同样的方法回收重组病毒。将所回收的病毒称为LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-LacZ(图2)。
(3)回收具有图3所示的病毒基因组的表达治疗基因和标记基因的SCR区域缺失重组牛痘病毒。具体而言，分别使用实施例2(2)中制作的LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-LacZ以及实施例1(2)中构建的转移载体质粒DNA(pTN-VGF-SP-IL12和pTN-VGF-SP-IL7)，代替BFP表达以DsRed表达消失作为指标，利用与实施例2(1)同样的方法回收各重组病毒。将所回收的各病毒称为LC16mO ΔSCR VGF-SP-IL12/O1L-SP-LacZ(以下称为“hIL12搭载牛痘病毒”)、LC16mO ΔSCR VGF-SP-IL7/O1L-SP-LacZ(以下称为“hIL7搭载牛痘病毒”)(图3)。为了进行纯化，使各重组病毒感染A549细胞或RK13细胞。在5％CO2存在下在37℃下培养2～5天后，回收感染细胞。将细胞冻融，进行超声波处理。使用OptiPrep(AxisShield公司)利用密度梯度离心分离法进行纯化。然后，利用RK13细胞测定各病毒的病毒效价。
(4)回收具有图4所示的病毒基因组的表达编码人IL-7的多核苷酸和编码人IL-12的多核苷酸的SCR结构域缺失重组牛痘病毒。
(4-1)具体而言，使用实施例2(2)中制作的LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-BFP和实施例1(2)中构建的转移载体质粒DNA pTN-VGF-SP-IL12，代替BFP表达以DsRed表达消失作为指标，利用与实施例2(1)同样的方法回收各重组病毒。将所回收的病毒称为LC16mO ΔSCR VGF-SP-IL12/O1L-SP-BFP。
(4-2)接着，使用实施例2(4-1)中制作的LC16mO ΔSCR VGF-SP-IL12/O1L-SP-BFP和实施例1(3)中构建的转移载体质粒DNA pTN-O1L-SP-IL7，代替BFP表达以BFP表达消失作为指标，利用与实施例2(1)同样的方法回收各重组病毒。将所回收的病毒称为LC16mO ΔSCR VGF-SP-IL12/O1L-SP-IL7(以下，在后述实施例中也称为“hIL12和hIL7搭载牛痘病毒”)(图4)。将各重组病毒用实施例2(3)的方法纯化后，利用RK13细胞测定各病毒的病毒效价。
(实施例3：基因重组牛痘病毒的肿瘤溶解性)
对于实施例2中制作的hIL12和hIL7搭载牛痘病毒，评价在各种人癌细胞中的溶解能力(细胞死亡能力)。另外，对于实施例2中制作的hIL12搭载牛痘病毒与hIL7搭载牛痘病毒这两种病毒的组合混合物，也同样地评价在各种人癌细胞中的溶解能力。
具体而言，首先，在96孔板(AGC Techno Class公司)中添加利用培养基(含有10％胎牛血清(GE Healthcare公司)和1％青链霉素(Life Technology公司)的下述记载的培养基)以达到1×104个/mL的方式悬浮的各细胞各100μL。培养一晚后，使用Opti-MEM(LifeTechnology公司)将1)hIL12和hIL7搭载牛痘病毒和2)将hIL12搭载牛痘病毒与hIL7搭载牛痘病毒以1:1的浓度组合而成的混合物(以下，称为“hIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物”)分别稀释至5×104PFU/mL、5×105PFU/mL和5×106PFU/mL。在各孔中分别添加20μL各病毒溶液，以MOI＝1.0、10、100的方式进行感染。作为对照，制作不添加细胞的孔、和添加Opti-MEM来代替病毒的孔(MOI＝0)。然后，在设定为CO2浓度5％、37℃的CO2温箱中培养5天。使用CellTiter-Glo发光法细胞活力检测试剂盒(Promega公司)测定5天后的细胞存活率。具体而言，按照上述检测试剂盒的操作规程，在各孔中分别添加100μL CellTiter-Glo试剂并静置30分钟后，将全部量移至96孔黑色酶标板(康宁公司)中，使用EnSpire(PerkinElmer公司)测定各孔的发光强度。在各孔中的细胞存活率的计算中，将未接种细胞的孔的值作为0％存活，将接种了细胞而未添加病毒的孔作为100％存活。
所评价的细胞为恶性黑色素瘤细胞RPMI-7951(ATCC HTB-66)、肺腺癌细胞HCC4006(ATCC CRL-2871)、肺癌细胞A549(ATCC CCL-185)、小细胞肺癌细胞DMS 53、肺鳞癌细胞NCI-H226(ATCC CRL-5826)、肾癌细胞Caki-1(ATCC HTB-46)、膀胱癌细胞647-V(DSMZACC 414)、头颈癌细胞Detroit 562(ATCC CCL-138)、乳腺癌细胞JIMT-1(DSMZ ACC 589)、乳腺癌细胞MDA-MB-231(ATCC HTB-26)、食道癌细胞OE33(ECACC 96070808)、胶质母细胞瘤U-87MG(ECACC 89081402)、神经母细胞瘤GOTO(JCRB JCRB0612)、骨髓瘤RPMI 8226(ATCCCCL-155)、卵巢癌细胞SK-OV-3(ATCC HTB-77)、卵巢癌细胞OVMANA(JCRB JCRB1045)、大肠癌细胞RKO(ATCC CRL-2577)、大肠癌细胞HCT 116、胰腺癌细胞BxPC-3(ATCC CRL-1687)、前列腺癌细胞LNCaP clone FGC(ATCC CRL-1740)、肝细胞癌JHH-4(JCRB JCRB0435)、间皮瘤NCI-H28(ATCC CRL-5820)、宫颈癌细胞SiHa(ATCC HTB-35)和胃癌细胞Kato III(RIKENBRC RCB2088)。
作为培养基，在RPMI-7951、HCC4006、DMS 53、NCI-H226、Caki-1、647-V、Detroit562、JIMT-1、OE33、U-87MG、GOTO、RPMI8226、SK-OV-3、OVMANA、RKO、HCT 116、BxPC-3、LNCaPclone FGC、JHH-4、NCI-H28和Kato III的情况下使用RPMI1640培养基(Sigma-Aldrich公司、R8758)，在A549和MDA-MB-231的情况下使用DMEM培养基(Sigma-Aldrich公司、D6429)，在SiHa的情况下使用EMEM培养基(ATCC 30-2003)。结果如图5-1～5-4所示。在此，由hIL12和hIL7搭载牛痘病毒产生的效果分为图5-1和5-2来记载，由hIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物产生的效果分为图5-3和5-4来记载。
其结果表明，hIL12和hIL7搭载牛痘病毒在进行试验的全部人癌细胞中具有使细胞死亡的能力(图5-1和5-2)。另外可知，关于hIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物，也在进行试验的全部人癌细胞中具有使细胞的能力(图5-3和5-4)。需要说明的是，在图5-1至图5-4中，每种细胞株从左起以MOI＝0、1、10、100的顺序显示出肿瘤溶解性。
(实施例4：由感染了基因重组牛痘病毒的癌细胞的蛋白质产生)
在使hIL12和hIL7搭载牛痘病毒感染癌细胞时，测定由癌细胞产生的人IL-7蛋白和人IL-12蛋白的浓度。此外，对于hIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物，也同样地在感染癌细胞时测定由癌细胞产生的人IL-7蛋白和人IL-12蛋白的浓度。
在人IL-7蛋白的测定中，具体而言，首先，将利用含有10％胎牛血清和1％青链霉素的RPMI1640培养基以达到1×104个/mL的方式悬浮的SK-OV-3卵巢癌细胞100μL接种到96孔板中。培养一晩后，利用Opti-MEM制备1)hIL12和hIL7搭载牛痘病毒、或2)hIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物，以MOI＝1.0的方式分别添加20μL使其感染细胞。然后，在设定为CO2浓度5％、37℃的CO2温箱中培养24小时，回收培养上清。使用表1中列出的ELISA试剂盒和EnSpire测定培养上清中含有的蛋白质浓度。
在人IL-12蛋白的测定中，将利用含有10％胎牛血清和1％青链霉素的RPMI1640培养基以达到1×105个/mL的方式悬浮的SK-OV-3卵巢癌细胞100μL接种到96孔板中。培养一晩后，利用Opti-MEM制备1)hIL12和hIL7搭载牛痘病毒、或2)hIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物，以MOI＝1.0的方式分别添加20μL使其感染细胞。然后，在设定为CO2浓度5％、37℃的CO2温箱中培养48小时，回收培养上清。使用表1中列出的ELISA试剂盒和EnSpire测定培养上清中含有的蛋白质浓度。
表1：实施例4中使用的ELISA试剂盒
[表1]
其结果表明，由添加了hIL12和hIL7搭载牛痘病毒的细胞、以及添加了hIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物的细胞可以产生人IL-12蛋白和人IL-7蛋白(表2-1和2-2)。
表2-1：培养上清中的人IL-12蛋白浓度
[表2-1]
表2-2：培养上清中的人IL-7蛋白浓度
[表2-2]
(实施例5：搭载编码小鼠IL-12的多核苷酸的转移载体质粒DNA的构建和搭载编码 小鼠IL-12的多核苷酸的基因重组牛痘病毒的构建)
(1)按照实施例1(2)记载的方法，构建转移载体质粒DNA pTN-VGF-SP-mIL12。在实施例1(2)记载的方法中，使用包含编码小鼠IL-12的多核苷酸(包含小鼠IL-12亚基p40、内部核糖体导入位点和小鼠IL-12亚基α的多核苷酸；序列号23)来代替编码人IL-12的多核苷酸(序列号7)，将该多核苷酸片段克隆至pTN-VGF-SP-BFP中。
(2)按照实施例1(3)记载的方法，构建转移载体质粒DNA pTN-O1L-SP-Luc2。在实施例1(3)记载的方法中，使用编码荧光素酶Luc2基因的多核苷酸(登录号DQ188840的第100位至第1752位)来代替包含大肠杆菌LacZ基因的多核苷酸(序列号9)，将该多核苷酸片段克隆至pTN-O1L-SP-BFP中。
(3)按照实施例2(2)的方法回收重组病毒。在实施例2(2)的方法中，使用LC16mOΔSCR VGF-p7.5-DsRed/O1L-SP-BFP和代替pTN-O1L-SP-LacZ的实施例5(2)中制作的pTN-O1L-SP-Luc2。将所回收的病毒称为LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-Luc2称为(以下将本病毒也称为“对照牛痘病毒”)。
(4)按照实施例2(3)的方法回收重组病毒。在实施例2(3)的方法中，使用代替LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-LacZ的实施例5(3)中制作的LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-Luc2和代替pTN-VGF-SP-IL12的实施例5(1)中制作的pTN-VGF-SP-mIL12。将所回收的病毒称为LC16mO ΔSCR VGF-SP-mIL12/O1L-SP-Luc2(以下也称为“mIL12搭载牛痘病毒”)。
(5)按照实施例2(4-1)的方法回收重组病毒。在实施例2(4-1)的方法中，使用LC16mO ΔSCR VGF-p7.5-DsRed/O1L-SP-BFP和代替pTN-VGF-SP-IL12的实施例5(1)中制作的pTN-VGF-SP-mIL12。将所回收的病毒称为LC16mO ΔSCR VGF-SP-mIL12/O1L-SP-BFP。
此外，按照实施例2(4-2)的方法回收重组病毒。在实施例2(4-2)的方法中，使用代替LC16mO ΔSCR VGF-SP-IL12/O1L-SP-BFP的上述中制作的LC16mO ΔSCR VGF-SP-mIL12/O1L-SP-BFP和pTN-O1L-SP-IL7。将所回收的病毒称为LC16mO ΔSCR VGF-SP-mIL12/O1L-SP-IL7(以下也称为“mIL12和hIL7搭载牛痘病毒”)。
(实施例6：荷瘤人源化小鼠中的基因重组牛痘病毒的抗肿瘤效果)
对于hIL12和hIL7搭载牛痘病毒，使用移植了人癌细胞的人源化小鼠(通过在重度免疫缺陷小鼠中移入人造血干细胞而将免疫系统置换为人免疫细胞的小鼠)，对在生物体内的抗肿瘤效果进行评价。
具体而言，首先，为了制作人源化小鼠，对于使用X射线照射装置以2.0戈瑞的强度进行了X射线照射的NOG小鼠(NOD/Shi-scidIL-2RγKO Jic、雌性、6周龄、日本CLEA株式会社)，从尾静脉注射移入3×104个人脐带血来源的造血干细胞(Lonza公司)。移入13周后，在小鼠的右背侧皮下注射移植以3×107个/mL悬浮在PBS中的人肺癌细胞NCI-H1373(ATCCCRL-5866)100μL。癌细胞移植后使用游标卡尺测定肿瘤径，按照各组的肿瘤体积(短径mm×短径mm×长径mm×0.52)的平均值为37mm3至47mm3的方式进行分组。在同一天向肿瘤内注射用PBS稀释至1.0×108PFU/mL的浓度的hIL12和hIL7搭载牛痘病毒20μL(表中记作“hIL12和hIL7搭载VV施用组”)。将在肿瘤内施用了PBS 20μL的组作为溶剂(PBS)施用组。对于各小鼠，每2～4天使用游标卡尺测定肿瘤径，基于上式算出肿瘤体积，利用下式算出每个个体在病毒施用后14天的肿瘤体积变化率(％)(n＝7～8)：
病毒施用后14天的肿瘤体积变化率(％)＝100(％)×病毒施用后14天的肿瘤体积(mm3)/病毒施用日的肿瘤体积(mm3)。
在病毒施用后14天的肿瘤体积变化率(％)的各组的平均值小于100、并且利用配对t检验对各组的病毒施用后14天的肿瘤体积与病毒施用日的肿瘤体积进行检验并确认到显著差异(将p值<0.05作为有显著差异)的情况下，判定为具有肿瘤缩减效果。
需要说明的是，在本实施例中，作为与hIL12和hIL7搭载牛痘病毒(2×106PFU/个体)相对比的比较病毒，以相同的注射量(20μL)和稀释溶液(PBS)使用对照牛痘病毒(2×106PFU/个体)、hIL12搭载牛痘病毒(2×106PFU/个体)或hIL7搭载牛痘病毒(2×106PFU/个体)(表中，分别记作“对照VV施用组”、“hIL12搭载VV施用组”、“hIL7搭载VV施用组”)。
其结果，在施用hIL12和hIL7搭载牛痘病毒的组中，显示出病毒施用后14天的肿瘤体积变化率的平均值小于100％。此外，利用配对t检验对病毒施用后14天的肿瘤体积与病毒施用日的肿瘤体积进行检验的结果确认到显著差异，由此判定为具有肿瘤缩减效果(表3)。因此表明，hIL12和hIL7搭载牛痘病毒的施用具有肿瘤缩减效果。另一方面，在施用hIL12搭载牛痘病毒或hIL7搭载牛痘病毒中的任意一者的组中，未确认到肿瘤缩减效果(表3)。
表3：hIL12和hIL7搭载牛痘病毒在荷瘤人源化小鼠中引起的肿瘤体积变化率(％)
[表3]
(实施例7：同系荷瘤小鼠模型中的基因重组牛痘病毒的完全缓解导入效果)
(1)关于mIL12和hIL7搭载牛痘病毒
关于mIL12和hIL7搭载牛痘病毒，使用皮下移植了同系小鼠癌细胞株的小鼠(同系荷瘤小鼠)，对生物体内的完全缓解导入效果进行评价。需要说明的是，已知人IL-12对小鼠的免疫细胞无反应，因此使用搭载有编码小鼠IL-12的多核苷酸来代替编码人IL-12的多核苷酸的基因重组牛痘病毒(在实施例5中制作)。
具体而言，首先，在C57BL/6J小鼠(雄性、5-7周龄、日本查尔斯河公司)的右腹侧皮下移植用PBS制备为4×106个/mL的小鼠肺癌细胞LL/2(LLC1)(ATCC CRL-1642)(以下称为LLC1)50μL。利用与实施例6同样的方法算出肿瘤体积，按照各组的肿瘤体积的平均值为50mm3至60mm3的方式进行分组。次日，对12只小鼠进行用PBS稀释为6.7×108PFU/mL的浓度的mIL12和hIL7搭载牛痘病毒30μL的肿瘤内注射(2×107PFU、表中记作“mIL12和hIL7搭载VV施用组”)。在初次施用的2天后和4天后也实施同样的病毒的肿瘤内注射。将代替病毒而进行PBS 30μL肿瘤内施用的组作为溶剂(PBS)施用组。
使用游标卡尺每周两次测定肿瘤径，算出肿瘤体积。将最终在病毒初次施用的27天后的观察时通过触诊确认不到肿瘤的情况定义为完全缓解，计测显示出完全缓解的个体的数量。关于在试验期间中组的平均肿瘤体积超过1700mm3的组，从动物伦理上的观点出发使其安乐死。需要说明的是，在本实施例中，作为与mIL12和hIL7搭载牛痘病毒(2×107PFU/次、施用3次)相对比的比较病毒，以相同的注射量(30μL/一次施用)和稀释溶液(PBS)使用对照牛痘病毒、mIL12搭载牛痘病毒或hIL7搭载牛痘病毒(分别为2×107PFU/次、施用3次)(表中，分别记作“对照VV施用组”、“mIL12搭载VV施用组”、“hIL7搭载VV施用组”)。
其结果，在施用mIL12和hIL7搭载牛痘病毒的组中，最终3例个体达到完全缓解。另一方面，在施用比较病毒的组中，未得到完全缓解的个体(表4-1)。因此表明，在同系荷瘤小鼠模型中，施用mIL12和hIL7搭载牛痘病毒时，与hIL7搭载牛痘病毒或mIL12搭载牛痘病毒相比具有更高的完全缓解导入效果。
表4-1：通过施用mIL12和hIL7搭载牛痘病毒而达到完全缓解的小鼠个体数
[表4-1]
(2)关于mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物
关于mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的1:1混合物(以下，记作“mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物”)，使用同系荷瘤小鼠对生物体内的完全缓解导入效果进行评价。
与(1)同样地实施。但是，移植以达到8×106个/mL的方式悬浮的小鼠肺癌细胞LLC1。此外，代替稀释为6.7×108PFU/mL的浓度的mIL12和hIL7搭载牛痘病毒30μL(2×107PFU)，使用mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物(在PBS中将各病毒稀释为6.7×108PFU/mL)30μL(各2×107PFU/次、施用3次)(表中，记作“mIL12搭载VV与hIL7搭载VV的混合物的施用组”)。小鼠的个体数使用7只。作为比较病毒，分别以30μL的注射量使用对照牛痘病毒(4×107PFU/次、施用3次)、mIL12搭载牛痘病毒与对照牛痘病毒的1:1混合物(各2×107PFU/次、施用3次)、或者hIL7搭载牛痘病毒与对照牛痘病毒的1:1混合物(各2×107PFU/次、施用3次)(表中，分别记作“对照VV施用组”、“mIL12搭载VV与对照VV的混合物的施用组”、“hIL7搭载VV与对照VV的混合物的施用组”)。
其结果，在施用mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物的组中，4例个体达到完全缓解。在施用mIL12搭载牛痘病毒与对照牛痘病毒的混合物的组中，仅一例完全缓解，在施用其他比较病毒的组中，无完全缓解例(表4-2)。因此表明，在同系荷瘤小鼠模型中，与包含hIL7搭载牛痘病毒或mIL12搭载牛痘病毒中的任意一者的混合物相比，mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物具有更高的完全缓解导入效果。
表4-2：通过施用mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物而达到完全缓解的小鼠个体数
[表4-2]
(实施例8：同系荷瘤小鼠模型中的基因重组牛痘病毒的获得性免疫效果(由获得 性免疫产生的肿瘤排斥效果))
(1)关于mIL12和hIL7搭载牛痘病毒：
对于进行了mIL12和hIL7搭载牛痘病毒处置的结果完全缓解的小鼠，进行相同癌细胞的再移植实验，评价由病毒引起的获得性免疫效果。
具体而言，首先，按照实施例7制作LLC1荷瘤小鼠，对其进行mIL12和hIL7搭载牛痘病毒的肿瘤内施用(但是，关于病毒的肿瘤内注射，除了在初次施用的2天后和4天后以外，在1天后、3天后也实施病毒的肿瘤内注射(总计5次)；表中称为“mIL12和hIL7搭载VV施用组”)。对于在病毒最终施用的23天后确认到完全缓解并在最终施用的51天后仍维持完全缓解状态的个体、以及与这些个体周龄相符的非病毒接种小鼠(对照组)，将用PBS悬浮至8×106个/mL的LLC1癌细胞50μL移植于皮下。按照实施例6算出肿瘤体积，计测最终在LLC1移植后第14天的观察时通过目视和触诊确认到肿瘤形成的个体的数量，求出肿瘤植活的小鼠的个体数/接种了癌细胞的小鼠的个体数的比例。在本实施例中，在对照组与病毒施用组中进行费舍尔精确检验，在有显著差异(小于5％)情况下评价为具有获得性免疫效果。
其结果，在对照组中，所有10例中在10例中全部形成了皮下肿瘤，而在mIL12和hIL7搭载病毒施用组中，所有10例中在6例中无论通过目视还是触诊均未确认到再移植的LLC1癌细胞的肿瘤形成(表5-1)(P<0.05、费舍尔精确检验)。因此，通过本实施例确认到由mIL12和hIL7搭载牛痘病毒的施用产生的获得性免疫效果。
表5-1：完全缓解小鼠中的癌细胞移植试验的结果
[表5-1]
(2)关于mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物：
对于进行mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物处置的结果完全缓解的小鼠，进行相同癌细胞的再移植实验，评价获得性免疫效果。
具体而言，与(1)同样地实施。但是，代替通过施用mIL12和hIL7搭载牛痘病毒而完全缓解的小鼠，使用按照实施例7(2)施用mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物(分组的1天后、3天后、5天后、总计3次)而完全缓解的小鼠(表中，称为“mIL12搭载VV与hIL7搭载VV的混合物的施用组”)。癌细胞的再移植在病毒最终施用后74天后(在最终施用的24天后判定完全缓解)进行。
其结果，在癌细胞再移植14天后，在对照组中，8例中全部形成了皮下肿瘤，而在mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物施用组中，10例中在8例中无论通过目视还是触诊均未确认到再移植的LLC1癌细胞的肿瘤形成(表5-2)(P<0.05、费舍尔精确检验)。
因此，通过本实施例确认到由mIL12搭载牛痘病毒与hIL7搭载牛痘病毒的混合物的施用产生的获得性免疫效果。
表5-2：完全缓解小鼠中的癌细胞移植试验的结果
[表5-2]
产业上的可利用性
本发明的牛痘病毒、药物组合物和组合试剂盒对各种癌症的预防或治疗有用。
序列表自由文本
序列表的数字标题<223>中记载了“人工序列(Artificial Sequence)”的说明。
序列号1～6和10～15所表示的核苷酸序列为引物。
序列号7、8和9所表示的碱基序列分别为包含人IL-12基因的多核苷酸、包含人IL-7基因的多核苷酸和包含大肠杆菌LacZ基因的多核苷酸。序列号7中，第14位～第1000位的碱基序列对应于IL-12的编码p40亚基的区域，第1606位～第2367位的碱基序列对应于IL-12的编码亚基α的区域。
序列号16和17所表示的核苷酸序列为与序列号7～9的各基因编码区域连接的限制酶位点。
序列号18所表示的氨基酸序列为缺失了4个SCR结构域的B5R蛋白。
序列号19、20所表示的碱基序列为LC16mO VGF-SP-LucGFP/O1L-p7.5-DsRed的两末端环序列的序列。
序列号21所表示的碱基序列为LC16mO VGF-SP-LucGFP/O1L-p7.5-DsRed的除两末端环序列以外的序列。
序列号22所表示的碱基序列为包含p7.5k启动子和DsRed片段的DNA片段。
序列号23所表示的碱基序列为包含小鼠IL-12基因的多核苷酸。
序列表
<110> 安斯泰来制药株式会社（Astellas Pharma Inc.）
国立大学法人鸟取大学（NATIONAL UNIVERSITY CORPORATION TOTTORI UNIVERSITY）
<120> 新型基因重组牛痘病毒（Novel genetically engineered vaccinia viruses）
<130> A17006A00
<150> JP 2016-107481
<151> 2016-05-30
<160> 23
<170> PatentIn version 3.5
<210> 1
<211> 37
<212> DNA
<213> Artificial Sequence
<220>
<223> pTagBFP-N vector forward primer
<400> 1
atggccggac cggccaccgg tcgccaccat gagcgag 37
<210> 2
<211> 41
<212> DNA
<213> Artificial Sequence
<220>
<223> pTagBFP-N vector reverse primer
<400> 2
tcgaattcgc tagcggccgc ttaattaagc ttgtgcccca g 41
<210> 3
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> B4R forward primer
<400> 3
cagtcacgac gttgtaaa 18
<210> 4
<211> 73
<212> DNA
<213> Artificial Sequence
<220>
<223> B4R reverse primer
<400> 4
catgcgcacc ttgaagcgca tgaactcctt gatgacgtcc tcggaggagg ccatttttat 60
ttatgagcgt taa 73
<210> 5
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> DsRed forward primer
<400> 5
gagttcatgc gcttcaaggt 20
<210> 6
<211> 99
<212> DNA
<213> Artificial Sequence
<220>
<223> DsRed reverse primer
<400> 6
ctcaattgat tctagctata agtctttaat cttttgatac ttgttcgtta ttaattatta 60
attattttaa cggatttata tctacaggaa caggtggtg 99
<210> 7
<211> 2379
<212> DNA
<213> Artificial Sequence
<220>
<223> polynucleotide comprising human IL-12
<400> 7
accggtcgcc accatgtgtc atcagcaact tgtcatcagc tggttttcac tcgtgtttct 60
tgccagccct ttggtagcga tttgggaact caagaaagac gtgtatgtcg ttgagctgga 120
ttggtatcct gatgcccctg gagagatggt ggtgctgacc tgtgatactc ccgaagagga 180
tgggataacc tggacccttg accagtcctc tgaagtcctg gggagtggca aaactctgac 240
gattcaggtg aaagagtttg gcgacgctgg ccagtacacc tgtcataagg gtggcgaagt 300
actgtctcat tcccttctgc tgctgcacaa gaaagaggac gggatttggt caacagacat 360
tctgaaagac cagaaggaac cgaagaacaa aacgttcctc cgctgtgagg cgaagaacta 420
ctcaggcaga ttcacatgct ggtggctgac tacaatcagc actgatctga cgttctccgt 480
caagagttct cgaggaagct ctgatccgca aggagtcaca tgcggtgcag ccactctgag 540
cgctgagagg gtgagaggag acaacaaaga gtacgagtat tccgtggagt gccaggaaga 600
ttccgcctgt ccagccgcag aagaaagctt gcctatcgag gtgatggttg atgctgttca 660
caaactcaag tacgagaatt acacctccag cttctttatc cgggacatca tcaaacccga 720
tccacccaag aatctgcagt tgaaacccct caagaactca cgtcaggttg aggtgtcttg 780
ggagtatccc gatacatggt caacaccaca cagttatttc agcctgacct tttgcgtcca 840
ggtgcaaggg aagagcaagc gcgaaaagaa agacagggtg ttcaccgaca agactagtgc 900
taccgtgatt tgccggaaga atgccagcat atctgttaga gcacaggaca ggtactactc 960
ctcctcttgg agtgaatggg catcagtacc atgcagctga tgcatctagg gcggccaatt 1020
ccgcccctct ccctcccccc cccctaacgt tactggccga agccgcttgg aataaggccg 1080
gtgtgcgttt gtctatatgt gattttccac catattgccg tcttttggca atgtgagggc 1140
ccggaaacct ggccctgtct tcttgacgag cattcctagg ggtctttccc ctctcgccaa 1200
aggaatgcaa ggtctgttga atgtcgtgaa ggaagcagtt cctctggaag cttcttgaag 1260
acaaacaacg tctgtagcga ccctttgcag gcagcggaac cccccacctg gcgacaggtg 1320
cctctgcggc caaaagccac gtgtataaga tacacctgca aaggcggcac aaccccagtg 1380
ccacgttgtg agttggatag ttgtggaaag agtcaaatgg ctctcctcaa gcgtattcaa 1440
caaggggctg aaggatgccc agaaggtacc ccattgtatg ggatctgatc tggggcctcg 1500
gtgcacatgc tttacatgtg tttagtcgag gttaaaaaaa cgtctaggcc ccccgaacca 1560
cggggacgtg gttttccttt gaaaaacacg atgataagct tgccaatgtg gcctcctggt 1620
agtgcgtcac agccaccacc cagtcccgca gcagctactg gattgcatcc agctgctaga 1680
cctgtctctc tgcaatgtag gctgagcatg tgtccagcta ggagcttgct gcttgttgcc 1740
acgcttgtgc tcctggacca cctgtcattg gcacgcaatc tgcccgttgc cactcccgat 1800
ccaggcatgt ttccgtgcct ccatcactct cagaacctcc tgcgggcagt cagcaatatg 1860
ctgcagaaag cgaggcaaac actggagttt tacccgtgta ccagcgaaga gatagatcac 1920
gaggacatta ccaaggacaa gacgtcaaca gtggaagctt gtctgcctct ggagctcaca 1980
aagaatgagt cctgcctgaa tagccgtgaa accagtttca tcaccaatgg gtcttgcttg 2040
gctagtcgca aaacatcctt catgatggca ttgtgccttt cctccatcta tgaggatctc 2100
aagatgtatc aggtggagtt caaaaccatg aacgccaaac tgctgatgga tcccaaacga 2160
cagatctttc tcgatcagaa catgcttgcc gtaatcgacg aactgatgca agccctgaac 2220
ttcaacagcg aaactgtgcc tcagaagtct agccttgaag agcccgactt ctacaaaacc 2280
aagatcaagc tgtgcatact cctgcatgcc tttcggatta gagccgtgac tattgacaga 2340
gtcatgtcct acctgaacgc ctcatgagct agcgaattc 2379
<210> 8
<211> 559
<212> DNA
<213> Artificial Sequence
<220>
<223> polynucleotide comprising human IL-7
<400> 8
accggtcgcc accatgtttc atgtctcttt tcggtacatc tttggacttc cacccctgat 60
actggtgttg ctgcctgtag cctcatcaga ctgtgacatt gaaggcaaag acggcaaaca 120
gtatgagagc gttctcatgg tgagcatcga tcagctcctt gactccatga aggaaattgg 180
ctccaattgc ctcaataacg agttcaactt cttcaaacgt cacatttgcg atgccaacaa 240
agaggggatg ttcctgttta gagccgctcg aaagctcagg cagttcctga agatgaactc 300
tactggggat ttcgatctgc atctgctgaa agtgagtgaa gggactacga tactgctgaa 360
ttgtaccgga caagtcaaag gaagaaagcc cgcagctttg ggtgaagcgc aaccgacaaa 420
gagtctggag gagaataaga gcctgaaaga acagaagaag ctcaatgacc tttgctttct 480
gaaacgcctt ttgcaggaga tcaagacctg ttggaacaag atcctgatgg gtacaaagga 540
gcactgagct agcgaattc 559
<210> 9
<211> 3082
<212> DNA
<213> Artificial Sequence
<220>
<223> Codon optimized LacZ
<400> 9
accggtcgcc accatggacc cggtggtgct gcagaggcgg gattgggaga atcctggggt 60
gacgcagctg aatcggctgg ctgctcaccc accatttgca tcatggagaa attccgaaga 120
ggcccggacc gaccgcccct ctcagcagct cagaagtctt aatggagaat ggcgcttcgc 180
atggtttcct gctcccgagg ctgtaccgga aagttggctc gagtgcgatt tgcccgaggc 240
agataccgtc gtggttccct ccaactggca gatgcacggc tatgatgccc ctatctacac 300
caatgtcact taccctataa cagtgaaccc accctttgtg cctaccgaga atcccaccgg 360
atgctacagt ctgacattta acgtggacga gtcttggctg caggaaggcc agactagaat 420
catcttcgat ggtgtcaaca gcgcttttca tctgtggtgc aacgggcgtt gggtgggtta 480
cggccaagac agtaggctcc cttctgaatt cgatctctct gccttcctgc gggccggtga 540
gaatagactt gccgttatgg ttctgcgttg gagcgacggt tcctacctgg aggaccagga 600
tatgtggagg atgtctggca ttttccgaga tgtgagcctc cttcacaaac ctaccactca 660
aatctccgac tttcatgttg ccacaaggtt caacgacgac ttttcacgcg ctgttctgga 720
ggccgaggtc caaatgtgcg gcgaactgcg cgattatctg cgcgtgactg tgagcctttg 780
gcaaggagag acacaggtgg catcaggcac cgcacccttc ggcggagaaa tcatcgacga 840
acggggagga tatgctgata gggttactct taggctgaat gtagaaaacc ccaagctctg 900
gtctgcagaa atacctaacc tctatcgcgc agttgtggaa ctgcacacgg cagacgggac 960
cctgattgaa gccgaagcct gtgacgtcgg cttccgtgaa gtgcgcatcg agaatgggct 1020
gctccttctt aacggtaagc cactgttgat cagaggcgtg aataggcatg agcatcatcc 1080
gctccacgga caggtgatgg atgagcagac aatggttcag gacatactct tgatgaaaca 1140
gaacaacttc aatgccgtgc gctgtagcca ctaccctaat cacccactgt ggtataccct 1200
gtgtgacagg tacggcctgt atgtcgtgga tgaggcaaac attgaaactc atggcatggt 1260
gccaatgaat cggctgacag atgaccccag atggctgccc gccatgtcag agcgtgtgac 1320
caggatggta cagcgggaca gaaatcaccc cagtgtcata atctggtccc ttgggaacga 1380
atcagggcat ggtgcaaacc acgatgctct gtaccgctgg attaagagcg ttgaccctag 1440
tcggccagtg cagtatgaag gtggaggcgc cgataccact gcaactgaca ttatttgccc 1500
aatgtacgct cgggtcgacg aggatcaacc gttccctgcg gtcccaaagt ggagcattaa 1560
gaaatggctg tctttgcctg gagaaacacg cccgctgatt ctgtgcgaat atgcccacgc 1620
aatggggaac tccctgggcg ggtttgcaaa gtattggcag gcttttcgcc agtatccacg 1680
actgcaggga ggctttgtgt gggactgggt agatcagagc ctgatcaaat acgacgaaaa 1740
tggcaatcca tggtccgcct atggaggtga ctttggtgat acccctaatg acaggcagtt 1800
ttgcatgaac ggactcgtct ttgcagatcg aactccacat ccggccctga ctgaggccaa 1860
gcatcagcag caattcttcc agtttcggct gtctgggcag accattgagg tgacttccga 1920
gtacttgttt cgacacagcg acaatgagct gctgcactgg atggtggccc tcgatggcaa 1980
accactggcc tcaggagagg tgcccctgga tgtagcgccc caggggaaac agcttatcga 2040
gttgcccgaa ctgccccaac ccgagtctgc tgggcaactc tggcttaccg tgcgagtcgt 2100
tcagccaaat gccactgcct ggtccgaggc tggccacatt agcgcatggc agcagtggag 2160
actggctgag aacctcagcg ttacccttcc cgcagcctct cacgccatcc ctcacttgac 2220
cactagtgag atggacttct gtatcgagct gggcaacaaa cgctggcagt ttaacagaca 2280
gtcaggcttc ttgtcccaga tgtggattgg cgacaagaag cagctgttga cccctttgcg 2340
ggatcagttc acaagggcgc ctctggacaa tgacatcgga gtgagcgagg ctacacgaat 2400
agatccaaac gcgtgggtcg agaggtggaa ggcggctggg cactaccaag ctgaagcggc 2460
cctgttgcaa tgtaccgccg atacgctcgc cgatgccgtc ctcattacga cagcccacgc 2520
ttggcagcac cagggcaaaa cactgtttat ctcccgtaag acatacagaa tcgatggcag 2580
cggtcaaatg gccattacgg tagacgtgga agttgcgtca gatacacccc atcccgcgag 2640
gatcggactg aactgtcaat tggcccaagt cgcagagaga gtgaactggc tgggactcgg 2700
gcctcaggag aattatccag accggctcac agccgcttgc ttcgataggt gggaccttcc 2760
actctctgat atgtacaccc catacgtgtt cccctcagag aatggcctgc ggtgtgggac 2820
acgagaactg aactacggac cgcatcagtg gagaggggac ttccagttca acatcagccg 2880
gtatagtcag cagcagctga tggaaacgtc ccatagacat ctgctgcacg ctgaggaagg 2940
gacatggctg aacattgacg ggttccacat gggaataggt ggcgatgaca gctggtcccc 3000
tagcgtaagc gccgagtttc aactgagtgc tgggagatat cattaccaac tggtctggtg 3060
ccagaaatga gctagcgaat tc 3082
<210> 10
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> VGF forward primer
<400> 10
ggtaacgcta tcgaaacgac 20
<210> 11
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> VGF reverse primer
<400> 11
ttagttcgtc gagtgaacct 20
<210> 12
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> O1L forward primer
<400> 12
acagggatta agacggaaag 20
<210> 13
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> O1L reverse primer
<400> 13
gtcaacaagc atcttccaac 20
<210> 14
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> B5R forward primer-for PCR
<400> 14
cgtataatac gttggtctat 20
<210> 15
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> B5R reverse primer-for PCR
<400> 15
gatcgtgcca atagtagtta 20
<210> 16
<211> 13
<212> DNA
<213> Artificial Sequence
<220>
<223> 5' restriction enzyme site in SEQ ID NOS: 7 to 9
<400> 16
accggtcgcc acc 13
<210> 17
<211> 12
<212> DNA
<213> Artificial Sequence
<220>
<223> 3' restriction enzyme site in SEQ ID NOS: 7 to 9
<400> 17
gctagcgaat tc 12
<210> 18
<211> 101
<212> PRT
<213> Artificial Sequence
<220>
<223> 4 SCR domains deleted B5R protein
<400> 18
Met Lys Thr Ile Ser Val Val Thr Leu Leu Cys Val Leu Pro Ala Val
1 5 10 15
Val Tyr Ser Thr Cys Val Arg Ser Asn Glu Lys Phe Asp Pro Val Asp
20 25 30
Asp Gly Pro Asp Asp Glu Thr Asp Leu Ser Lys Leu Ser Lys Asp Val
35 40 45
Val Gln Tyr Glu Gln Glu Ile Glu Ser Leu Glu Ala Thr Tyr His Ile
50 55 60
Ile Ile Val Ala Leu Thr Ile Met Gly Val Ile Phe Leu Ile Ser Val
65 70 75 80
Ile Val Leu Val Cys Ser Cys Asp Lys Asn Asn Asp Gln Tyr Lys Phe
85 90 95
His Lys Leu Leu Pro
100
<210> 19
<211> 104
<212> DNA
<213> Artificial Sequence
<220>
<223> Partial genome sequence of Vaccinia virus
<400> 19
tagtaaaatt aaattaatta taaaattata tatataattt actaacttta gttagataaa 60
ttaataatat ataagtttta gtacattaat attatatttt aaat 104
<210> 20
<211> 104
<212> DNA
<213> Artificial Sequence
<220>
<223> Partial genome sequence of Vaccinia virus
<400> 20
atttaaaata taatattaat gtactaaaac ttatatatta ttaatttatc taactaaagt 60
tagtaaatta tatatataat tttataatta atttaatttt acta 104
<210> 21
<211> 202489
<212> DNA
<213> Artificial Sequence
<220>
<223> Partial genome sequence of modified vaccinia virus
<400> 21
attttattta gtgtctagaa aaaaatgtgt gacccatgac tgtaggaaac tctagagtgt 60
aagaaagatc gatcgcttta tagagaccat cagaaagagg tttaatattt ttgtgagacc 120
atcgaagaga gaaagagata aaactttttt acgactccat cagaaagagg tttaatattt 180
ttgtgagacc atcgaagaga gaaagagata aaactttttt acgactccat cagaaagagg 240
tttaatattt ttgtgagacc atcgaaggag aaagagataa aactttttta cgactccatc 300
agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta 360
cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa 420
aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag 480
aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca 540
tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt 600
tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt 660
ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc 720
agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta 780
cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa 840
aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag 900
aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca 960
tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt 1020
tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt 1080
ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc 1140
agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta 1200
cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa 1260
aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag 1320
aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca 1380
tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt 1440
tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt 1500
ttaatatttt tgtgagacca tcgaagagag aaagagaaag agatagttag tctagatatt 1560
tttcttagta caaaagtcaa tgttttaaaa tatatggaca agaatttgtc tgtataaaaa 1620
cttgtgtgaa attttgtacc aaagaaaaaa tgtgagcagt atcccctaca tggattttac 1680
tagatcattt atataccaaa aaatattata cgatctacgt tttattatat gattttaacg 1740
tgtaaattat aaacattatt ttatgatata caattgtctg gtaacctaga tgggcatagg 1800
ggatgttgat aagctcgacg agtatatgtt gttggacgtt attgtttaag aaatagttga 1860
tgcatcagaa agagaataaa aaatatttta gtgagaccat cgaagagaga aagagataaa 1920
acttttttac gactccatca gaaagaggtt taatattttt gtgagaccat cgaagagaga 1980
aagagaataa aaatatttta tgactccatt gaagagagaa agagaaaatg agaatgagaa 2040
taaaaatatt ttagtgacac catcagaaag aggtttaata tttttgtgag accatcgaag 2100
agagaaagag aataaaaata ttttatgact ccattgaaga gagaaagaga aaatgagaat 2160
gagaataaaa atattttagt gacaccatca gaaagaggtt taatattttt tatgagacca 2220
tcaaagagag aaagaaaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 2280
agagaaagag aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa 2340
agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 2400
taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 2460
tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 2520
tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 2580
acttttttta tgagaccatc aaagagagaa agagaataaa aatatttttg taaaactttt 2640
tttatgagac catcaaagag agaaagagaa taaaaatatt tttgtaaaac tttttttatg 2700
agaccatcaa agagagaaag agaataaaaa tatttttgta aaactttttt tatgagacca 2760
tcaaagagag aaagagaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 2820
agagaaagag aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa 2880
agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 2940
taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 3000
tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 3060
tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 3120
acttttttta tgagaccatc aaagagagaa agagaataaa aatatttttg taaaactttt 3180
tttatgagac catcaaagag agaaagagaa taaaaatatt tttgtaaaac tttttttatg 3240
agaccatcaa agagagaaag agaataaaaa tatttttgta aaactttttt tatgagacca 3300
tcaaagagag aaagagaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 3360
agagaaagag aataaaaata tttttgtaaa acttttttta tgataccatc aaagagagaa 3420
agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 3480
taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 3540
tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 3600
tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 3660
acttttttta tgagaccatc aaagagagaa agagaataaa aatatttttg taaaactttt 3720
tttatgagac catcaaagag agaaagagaa taaaaatatt tttgtaaaac tttttttatg 3780
agaccatcaa agagagaaag agaataaaaa tatttttgta aaactttttt tatgagacca 3840
tcaaagagag aaagagaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 3900
agagaaagag aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa 3960
agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 4020
taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 4080
tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 4140
tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 4200
acttttttta tgagaccatc aaagagagaa agagaataaa aatatttttg taaaactttt 4260
tttatgagac catcaaagag agaaagagaa taaaaatatt tttgtaaaac tttttttatg 4320
agaccatcaa agagagaaag agaataaaaa tatttttgta aaactttttt tatgagacca 4380
tcaaagagag aaagagaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 4440
agagaaagag aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa 4500
agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 4560
taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 4620
tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 4680
tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 4740
acttttttta tgagaccatc agaaagaggt ttaatatttt tgtgataccc tgaaaggaaa 4800
taggaatagg aataggaata ggaatagtgt cataatcgta tcacactatt gagacagaaa 4860
aagaagaagt cgcgagaggt aactttttgt gaatgtagtt aagaacattt ttgttttgca 4920
aaccggaata tagtgtccgg tacacttttt taattcgtgg tgtgcctgaa tcgttcgatt 4980
aaccctactc atccaatttc agatgaatag agttatcgat tcagacacac gctttgagtt 5040
ttgttgaatc gatgagtgaa gtatcatcgg ttgcaccttc agatgccgat ccgtcgacat 5100
acttgaatcc atccttgacc tcaagttcag atgattcctt gcacatgtct ccgatacgaa 5160
cgctaaactc tagattcttg acacattttg tatcgacgat cgttgaaccg atgatatctt 5220
cgtaactcac tttcttatga gagatgttag acccgagtac tggatgggtc ttgatgtcgc 5280
tgtctttctc ttcttcgcta catctgatgt cgatagacac ctcacagtct ttgatcatag 5340
caagagcttc ttcatgagtg atcgcgggag agtccttacc ttgtcctggg gacacgctgg 5400
acaatctagc attcactgtg tttccatcag cggattctga gatggattta atctgaggac 5460
atttggtgaa tccaaagttc attctcagac ctccaccgat gatggagtaa taagtggtag 5520
gaggatctac atcctcgact gatgtggaat catcttctga ttccacctcg ggatctggat 5580
ctgactcgga ctctgtaatt tccgttacgg attggcaaat cttatcattg gtcggtgttt 5640
ggtcttgctt tgtgactttg ataataacat cgattcccat atgatgtttg ttttcttctt 5700
ccgtacacga ggaggaggat gaggatgatt gctgaagact ggcaggcata gcagctgccg 5760
ccaggcacat gcatgccagt acgatatatt gtttcataat tgctattgat tgagtactgt 5820
tctttatgat tctacttcct taccgtgcaa taaattagaa tatattttct acttttacga 5880
gaaattaatt attgtattta ttatttatgg gtgaaaaact tactataaaa agtgggtggg 5940
tttggaatta gtgatcagtt tatgtatatc gcaactaccg ggcatatggc tatcgacatc 6000
gagaacatta cccacatgat aagagattgt atcagtttcg tagtcttgag tattggtatt 6060
actatatagt atatagatgt cgcccactag agttactgtc tccgaatgcg gcatgatagt 6120
atcattcttt gctttcgtta actgtttgga ggaagaatct ttgttattgc atttaatctc 6180
gaaattcaga gtgcacacct ttctcctgta aagaaacctg aagtcgctac cttattaagg 6240
acggagaagt atccatcacg aaagacggga tcgcagtctt tatgattcat agtaatagtt 6300
agttccgacg ttgagatgga ttcgctgaga ccggtagtgg tcgtccgagt acacgacgtg 6360
tcgttaactg gatacagatt aatttccaca tcgatatagt taaaggtatt actgggtacg 6420
ggttcgcatt tatctgcgga agagacggtg tgagaatatg ttccgagacc acacggagaa 6480
cagatgacgt ctccggatac tccgtatcct attccacatt ttgtttggga aacacatgcc 6540
ttgcatccgg atgatccttt gagaagacaa taatatccgg gagagcattc acagattcta 6600
ttgtgagtcg tgttacacga tcgcgtcttc cgttacaact tagacaagcg ggtaaatgat 6660
tattgcgaga tgtgaaggta cccgaaccac acggcgtaca ttgtgtgtta gtcttgctat 6720
cgcataatct ggaagcgtat gttcccggac acaaattatg gcgtttgtat tcgttgtctt 6780
tacactttcc atcggatggt gcatgcggtg ctatatctct tccgtttatt attatacatg 6840
agagaaacaa tatatacgag tataatacgg acttcatgat ttaataatgt agtaatcgtc 6900
gtcttgttcc tgtttcctac ttctccaatc atatagatat tttctttcta tcatggataa 6960
tatttgtaat ggttctttcc gtacaacata ctgtttagat gatattgcgc ataatttccg 7020
gaggcaaata cgatagtcta gattgaccga tggtagactc taatttattg agtgctttgt 7080
cgacgagttt acttttacgc tccatcgata gatggcactg ttctatgaga tcgtcgtaca 7140
tgggaaatga aatgtgactg tctgaatgta tggctttaag atagctgtga taccgtatac 7200
aggtcggtgt cggagattcg aatctcttta aggcgactta tgtcacgatg atggaatcta 7260
tcttatcgaa tgatatattt ttcataaata cacttttata gtcctcgttt aaacagaatt 7320
tactatgtag ttccgcgaat gactcgtccc ttaataggca gtaggctagt atctttttta 7380
cgtagtaatc gtcgtaggga gagacatctt gtagaacaac gatttaatca taggtagaga 7440
tactttcagt ctgtggtgga tgatgtcatt cacaacatcc gccttgtata tgatgtttct 7500
gttttcaaac accaagtcga ataccgtctt tagtcggaag gttgatgtcg tatccgatgt 7560
atgaggcaac attgttgtta caattttgaa aggcggtatt atagtattcg tctttctgaa 7620
tgtcgaacct atctaataga taccgtagta tattgagagt gtatccttga ttatgtttta 7680
tgaatagata aagtagatgt tgtccttctt ccttttgttc gtgccaattg agtaacatta 7740
tgagaatatg acctgttgca caatcgttcc atgatgggtg tacaatcaag attattacgt 7800
atcctcgaga taaaagagca tacaccacac gaggactatg tttggtatac tgttgaaggt 7860
aagtgtgtaa ccgcgttaat gtttgctcca taatctatta tcgcgtagat gaatcgcttc 7920
tcggctcgca tcttagtgtg acttgacttg taataattgc tttcgtagaa cgtggatatg 7980
tgtttacagt agtaatgaag agaagtgagt tcatcctcgt cggcgcaatt agggtcggat 8040
cctttgtaca gaacgtaata gtttaagctc ccattgaatt tatatctaag ataacacagc 8100
aatagatcgg atgatttact aaagtcatca atggtgtccg ttagtatatc aaagatcttg 8160
ttatcgattg atagtggtca tccttgctat caaagttacg catgccgtgg tgtaacaata 8220
tctttaatac agatggatta aatcgtgtat tcatcgtata gcaatgtaat ggagagttac 8280
ctcgtttatt cagatcgcag tgtttaataa ctagcttaaa cagatgagac gatgtattca 8340
catcaaagaa cgtgaaatac atatgacaga cattgttgac agaaacgtga ccttcattct 8400
taccgtcgtc cataaatacg ttaggtatgt accacatact gtcgcgaacg atgcgtacaa 8460
tctcgtccat ctcataatga tttacttttt cataattaaa gatgtgaaag aaaaacagaa 8520
caatatattt ttttagtaat gtttatgcga gacatataaa ataaactccg tgtttatgat 8580
gccggtaaat gtttttatca tcttggacgg aatcgatttt gtaatatgtc atggaaacaa 8640
atgaaacagg acattatcgc tccatgataa attatttaat ggagtaataa agtatctcca 8700
tgggtaattt cgaaatcaag ttatcgtctg tattaatgtt gtccactatg gagtcgatcc 8760
tctcattgtt ctttacagtt tctgtaatga tggacgttag ttcttttttg taccatttga 8820
tgtcggattc tttgcgtatc tcagtctgtg gcgtttgctt tgtttaaata atatatcaaa 8880
catggagacg cctgatatgt aggcattctt cattctatta atgtctgctc tatagcgctt 8940
tagttcctta tgacgaccgg cgatatcata ctttacttta gaaggaaaat catcatctat 9000
gattaaggcg tatctgatac aggcgaataa tggttcagga tatagatagc gtatatctct 9060
attaaatgcg tcaatcatag tctctagagt gggatggtag ctaagtaata aatcaactat 9120
cctcgttttg ttttctcttt ggtaactgct tttctggatg gccgtattga ttatcgagcg 9180
tgatgttgta acactcgctc catattccaa taaccgcttt gcaaattgta tattattgac 9240
atcgaccgcg taatatagta gagttatcga tcatatctat atcatccatg tacttgctta 9300
gtatatcaaa tacatctatt agtatggttt cataacagtg atacccgcaa ttattaaatc 9360
tcgataatat cagaccgtac atacatagac ggccattgtt cgatacgtga tttacagccg 9420
cgtgtccata ttttccacga taaaccttac gacgtttaca tcgacgagat tattattaac 9480
aaagtagtcg tgtagaggat agttgttgtc cgtcgtctta tccatggttg ctccgttatc 9540
caacatgcat tgaatgatag gtatacttac catatcgccg taatgtaagt agtttatcaa 9600
catggcttgt acatcctgtt gtctaaatct ctttagaatg ttatcgatga tgtagtggtt 9660
atattctctg gaatcgtacg aagtaatact acgcattacg tcgacaagag tatgacgtct 9720
ctcaataaga agattaacga tttccatgtc tacattatat ggggttactc taaatcgctt 9780
gtttagataa tacgcctcta atatagggct gacgtcgtat actctacacg tgtccacatc 9840
ctttattaat aataatttaa caatctctat atctatggtt gagcaagacc agtagtattg 9900
gatgggtaaa gatcctcctt cgtctctgcc atggatggaa acattgttat cgatcaaaca 9960
tttaattaca tccttggata gagattgaga ttctctatga gacgatatat agtaatgaag 10020
agagttctta cacatatcac tgtcgtacat acaggtacga aatacgtaac cggtgctgta 10080
acattctgat ttaagaagcc atagcaatac ttctggtctc ggattaggcg tcgttacgta 10140
tatatccacc aatccgagac cattgattgc ataattcgta ttcttggacg gacgtatccg 10200
tttatccaca attaggtatt ttagcagacg taagtcgata ttatccgaat acagatcgaa 10260
atcatttata ttcgacttga gttcgttaga ggaatttgaa tagctggata tcagtagatg 10320
cacaatctga gattttacgt atctatgctt actgtatact cctagcggag ttaatccttc 10380
gttgtttcta caaagtctct cgactccgcg agagagtaac agccgaacaa tcttaatgtc 10440
tgtatcgcat ttattggaga cgtaacaatg tagcgcattg tttcctcgtc tatctatatg 10500
ttttgataag ttgtgacacg tttcaatttc tagttttatt tttttgtacg tcacatcttc 10560
atccagtaga cgacatagaa tagtgcactc tctaccacaa taatccatag ctattctggt 10620
gctaattatt cctatttcac gaaaaatgat aaaggcaatc attcctcata agatgataaa 10680
aagtgtagtg agagagcatg aaggagattt agtatttagc agtgcggata tgatccaaga 10740
gggtgagata gtcgttctcg ttcagaatct ttcgcagcat aagtagtatg tcgatatact 10800
tatcgttgaa gactcttcca gagacgatag ctgattgagt acaaagtcca atgattgcac 10860
gaagttcttc ggcggttttc atggagtcat ttctgatgaa acatttaatg atctccacgc 10920
aattgtccca cggaagtgaa tccttcaact caccaccaaa gagctccgtt gcatcagttc 10980
tgaaagagat gagaagcctg tagagagacc ctgcgctttc tctatgggtc catctatgag 11040
aaacccacag gatgtattca gtcagacaat gtctgacgtc ggccacggta ttcagggagt 11100
ccttagtagc gtggcaatga cagggtctga actgggcaca aggaaaggcc attgtgaagg 11160
tagacgaagg ttaacctgat ggtagacctg tagccgtcta tgctaataga gggctttaat 11220
ttccattttt taatggggtt gtggatgagg aatgagagtg atatcatatt gagatacgta 11280
gttatgtaga ggtgtatttc ctatattatt tactttcggt ttcatatttt accaactctt 11340
taataaattt cttttcacga tgcatcttat taaatgacgt tttctcataa gtggacatat 11400
agatgcagaa gtaatgaaga aaagtattac ctctatcatc tacataatta gggtctgctc 11460
ctttttttaa caacttatac agtacgtagt agtagtttat cggttttaaa tcaagtctag 11520
aatatatagt ggattaatat atttttatat tcgctaaagc tatctatact atcagaaagc 11580
atatcattct caacttcatc atgagttaaa tatttgtgta atggaatgtg accatcactg 11640
tcatgacata ctcctttaat aggtttttta aaacagatga ttcaaatcct tcattcatta 11700
gataacagtg taacggagtc gtaccttcta ctagtttgtt tatatcacag cattctacaa 11760
acagtctaaa caatagagaa gacggacaga ctttaacgta taaatgacac atgttatcga 11820
tattcgttga tgaattatta ttaaacgtag ttatgataaa tgattctaac gacatttctc 11880
gctagagata aaatctagta tcgtatcata ctcgcatagc atagtttttc ataattaata 11940
caatatttaa aagacttatt cggaaagtat tttaatacat gtatcatcga tggagatcca 12000
tatgaggagt cacttgtagt tcttcagtag taataacagt gctatcatcg atagtataat 12060
tatatgttgt tgtaattgga gtaactgttg gtagttcttc cgtggaatca ataattatac 12120
taacagcaat agtataatta tataaatatg ttccgttgat atcacatatt ttaatgaact 12180
catttctaac accctcagct atatctgtcc aattaaatgt agccaacaat ctactacgtt 12240
ctctttgatt gactacttgt acggtagcga cgctacacta tctttattgt cttctacatg 12300
ctccaattga atgtcatgat acaacgcagt ttttcttatg catgtttcat aacaccacga 12360
acatgtcgca gtaagataat ttttgtaaat tcatgattgc cggtcataaa caagcccgtc 12420
aataattgtg gctatatatt cagtttatag agcaaaataa ttaagcacaa tagcgcttaa 12480
tctcaaaata tgttatgttt atttttttca tattaaacat actggttaaa atcctctaaa 12540
ggctgatctt catctataaa tcaagatcat aattacattt agacagtggt ttcatgttta 12600
taaaaatgtt ctttttgtgt gaataaggaa tatactaatc aataatcaac catcgacccc 12660
attacgatag tatgcaggca accccccatt agagaggtac gtgtaatcag tctctccagt 12720
tttagtattt ttataagtca ttgttacata aacggctttt aaacagtctc ctcgataata 12780
agccatatct ggaaatttat taaatactcg agtcatttta cgcacggtca aaaaagtaag 12840
taatgtcgac gacttcttac attctataga aacacctaga atactcattt tcttttggaa 12900
aatatcctca gactctgatt tgaacaatgc acgacctata gtaaaccgtg accaataagt 12960
tatattagtc aatggtatat ccaaaccatc aagtgtggat agtacgccga tagtccagtc 13020
tttggtatcg atagtgtagt tattgaactg agaagttacc gtatagtctt tttggtcatc 13080
tctaaacaag gaaactaata cctctacact attgaacgat ttatcttccg taatgggtgg 13140
aataacggga atataaagtg gactagcgat ggatgaagtc acgaatataa gacacgctat 13200
taatccgtat atcatcattt tgatattact tataataacg atttgtttaa tttttagttt 13260
atactattaa ttgtaaatga tattattatt ttttttaagt attatcagct ttagtttata 13320
ctattactat ttgtaatatt tagacataga taaacgtgat aaaagtctat ttgtttatat 13380
ttattgcgga tagcagtatt tccctataaa aagtatacgt cctgtgttgt ctttaatcat 13440
gtacatgaat ggatggttta tgtagacctt cgtacgatat accatcgaaa agttagtcat 13500
aaatactcct gtaacggccg atgcttctgt atactcctca ttaacatcta taaacgtcgt 13560
atgtagaaat ttttctacag tgatagtttc attacacatc ttgctaaaat ctgcataata 13620
tccgaatata ttagtaagtc ctaaattttc taaaatcggt accagattat acggttctgt 13680
catttccact ttaaactttg gcatatacaa gtctatactt ttagtagata acataccaca 13740
ccatttttta aatttttcat ctgttatatt tttttctatg ttatatatac cttctatgtc 13800
gtccggtagt ataattacca tactagagtt tccctcgtat ggaatatcga taatagagaa 13860
tcctccgaat aattcattaa tatgtacata ttgcaagtta ttctcggtac ccaccatcat 13920
atcaacgctg gtaactatat tcttagaaat ataaaacttg tctgtatatg taagatgttt 13980
agaaaatgga tatttccaca ttgctttaaa atggacggcg ctaacaactg tcatacgagt 14040
attaatggat agcggactag tcaataagga attaatttta ccatttgtca ttgtcttaac 14100
ccattcgttg attagttcct ttgtttggtt agcattatta aagtttacag tttgaaaatc 14160
gtcttttatt ttttgtagga aggaggcatg gaactcgata ctatcgctac cgtatatttt 14220
atttgcggta gctagtgtcg cacaatacgg aatatctacg tccatgtcat tattgtcatc 14280
gggtgtattc tcattcatat tctctatata ttttgatagt tgttcagctg tagaaccagc 14340
tgctccatga tttagaatag ataaagtaga taaaatagaa actggagaaa tcaaaacatt 14400
ttcatccgtg tgttttaaga ttagttcttt aaagatatcc atggtataga ccaaacaata 14460
acgataacga tatatatcat aaataaataa tgttaaattt tagtttatgt ttgtaccccg 14520
tattcatact taacaaattg gtattgcgta cacaatcaat catattacat accattaata 14580
atgcaagcat aaaaaatcgt tagtagatgt ttctaaatat aggttccgta agcaaagaat 14640
ataagaatga agcggtaatg ataaaatcaa ttgttatcta aaatgatcat actcatttat 14700
tttattctat tatattaaca catacatttt taacagcaac acattcaata ttgtattgtt 14760
atttttatat tatttacaca attaacaata tattattagt ttatattact gaattaataa 14820
tataaaattc ccaatcttgt cataaacaca cactgagaaa cagcataaac acaaaatcca 14880
tcaaaaatgt tgataaatta tctgatgttg ttgttcgctg ctatgataat cagatcattc 14940
gccgatagtg gtaacgctat cgaaacgaca ttgccagaaa ttacaaacgc tacaacagat 15000
attccagcta tcagattatg cggtccagag ggagatggat attgtttaca cggtgactgt 15060
atccacgcta gagatattga cggtatgtat tgtagatgct ctcatggtta tacaggcatt 15120
agatgtcagc atgtagtatt agtagaattc ttacttgtac agctcgtcca tgccgagagt 15180
gatcccggcg gcggtcacga actccagcag gaccatgtga tcgcgcttct cgttggggtc 15240
tttgctcagg gcggactggg tgctcaggta gtggttgtcg ggcagcagca cggggccgtc 15300
gccgatgggg gtgttctgct ggtagtggtc ggcgagctgc acgctgccgt cctcgatgtt 15360
gtggcggatc ttgaagttca ccttgatgcc gttcttctgc ttgtcggcca tgatatagac 15420
gttgtggctg ttgtagttgt actccagctt gtgccccagg atgttgccgt cctccttgaa 15480
gtcgatgccc ttcagctcga tgcggttcac cagggtgtcg ccctcgaact tcacctcggc 15540
gcgggtcttg tagttgccgt cgtccttgaa gaagatggtg cgctcctgga cgtagccttc 15600
gggcatggcg gacttgaaga agtcgtgctg cttcatgtgg tcggggtagc ggctgaagca 15660
ctgcacgccg taggtcaggg tggtcacgag ggtgggccag ggcacgggca gcttgccggt 15720
ggtgcagatg aacttcaggg tcagcttgcc gtaggtggca tcgccctcgc cctcgccgga 15780
cacgctgaac ttgtggccgt ttacgtcgcc gtccagctcg accaggatgg gcaccacccc 15840
ggtgaacagc tcctcgccct tgctcaccat ggtggctgcg gccgccacgg cgatcttgcc 15900
gcccttcttg gccttaatga gaatctcgcg gatcttgcgg gcgtccaact tgccggtcag 15960
tcctttaggc acctcgtcca cgaacacaac accaccgcgc agcttcttgg cggttgtaac 16020
ctggctggcc acatagtcca cgatctcctt ctcggtcatg gttttaccgt gttccagcac 16080
gacgactgcg gcgggcagct cgccggcatc gtcgtcgggc aggccggcga ccccggcgtc 16140
gaagatgttg gggtgttgca gcaggatgct ctccagttcg gctggggcta cctggtagcc 16200
cttgtatttg atcaggctct tcagccggtc cacgatgaag aagtgctcgt cctcgtccca 16260
gtaggcgatg tcgccgctgt gcagccagcc gtccttgtcg atgagagcgt ttgtagcctc 16320
ggggttgtta acgtagccgc tcatgatcat ggggccacgg acgcacagct cgccgcgctg 16380
gttcacaccc agtgtcttac cggtgtccaa gtccaccacc ttagcctcga agaagggcac 16440
caccttgcct actgcgccag gcttgtcgtc cccttcgggg gtgatcagaa tggcgctggt 16500
tgtttctgtc aggccgtagc cctggcggat gcctggtagg tggaagcgtt tggccacggc 16560
ctcacctacc tccttgctga gcggcgcccc gccgctggcg atctcgtgca agttgcttag 16620
gtcgtacttg tcgatgagag tgctcttagc gaagaagcta aatagtgtgg gcaccagcag 16680
ggcagattga atcttatagt cttgcaagct gcgcaagaat agctcctcct cgaagcggta 16740
catgagcacg acccgaaagc cgcagatcaa gtagcccagc gtggtgaaca tgccgaagcc 16800
gtggtgaaat ggcaccacgc tgaggatagc ggtgtcgggg atgatctggt tgccgaagat 16860
ggggtcgcgg gcatgactga atcggacaca agcggtgcgg tgcggtaggg ctacgccctt 16920
gggcaatccg gtactgccac tactgttcat gatcagggcg atggttttgt cccggtcgaa 16980
gctctcgggc acgaagtcgt actcgttgaa gccgggtggc aaatgggaag tcacgaaggt 17040
gtacatgctt tggaagccct ggtagtcggt cttgctatcc atgatgatga tcttttgtat 17100
gatcggtagc ttcttttgca cgttgaggat cttttgcagc cctttcttgc tcacgaatac 17160
gacggtgggc tggctgatgc ccatgctgtt cagcagctcg cgctcgttgt agatgtcgtt 17220
agctggggcc acagccacac cgatgaacag ggcacccaac acgggcatga agaactgcaa 17280
gctattctcg ctgcacacca cgatccgatg gtttgtattc agcccatagc gcttcatagc 17340
ttctgccagc cgaacgctca tctcgaagta ctcggcgtag gtaatgtcca cctcgatatg 17400
tgcgtcggta aaggcgatgg tgccgggcac cagggcgtag cgcttcatgg ctttgtgcag 17460
ctgctcgccg gcggtcccgt cttcgagtgg gtagaatggc gctgggccct tcttaatgtt 17520
tttggcatct tccatggccc cggccgtgca ataaattaga atagtttttc aatttttggt 17580
acctcgacct tatttatatg ccaaaaaaaa aaaaaaaaaa gctgatccaa tttcgacgag 17640
actatcaacg ttcagaaaac ccaaacacta caacgtcata tatcccatct cccggtatta 17700
tgcttgtatt agtaggcatt attattatta cgtgttgtct attatctgtt tataggttca 17760
ctcgacgaac taaactactt atacaagata tggttgtgcc ataattttta taaatttttt 17820
ttatgagtat ttttacaaaa atgtataaag tgtatgtctt atgtatattt ataaaaatgc 17880
taaatatgcg atgtatctat gttatttgta tttatctaaa caatacctct acctctagat 17940
attatacaaa aattttttat ttcagcatat taaagtaaaa tctagttacc ttgaaaatga 18000
atacagtggg tggttccgta tcaccagtaa gaacataata gtcgaataca gtatccgatt 18060
gagattttgc atacaatact agtctagaaa gaaatttgta atcattttct gtgacgggag 18120
tccatatatc tgtatcatcg tctagtttat cagtgtccca tgctatattc ctgttatcat 18180
cattagttaa tgaaaataac tctcgtgctt cagaaaagtc aaatattgta tccatacata 18240
catctccaaa actatcgctt atacgtttat ctttaacgat acctatacct agatggttat 18300
ttactaacag acattttcca gatctattga ctataactcc tatagtttcc acatcaacca 18360
agtaatgatc atctattgtt atataacaat aacataactc ttttccattt ttatcagtat 18420
gtatatctat atcaacgtcg tcgttgtagt gaatagtagt cattgatcta ttatatgaaa 18480
cggatatgtc tagaacggca attgttttac gtccagttaa cactttcttt gatttaaagt 18540
ctagagtctt tgcaaacata atatccttat ccgactttat atttcctgta gggtggtata 18600
attttatttt gcctccacat atcggtgttt ccaaatatat tactagacaa tattccatat 18660
agttattagt taagggtacc caattagaac acgtacgctt attatcatca tttggatcgt 18720
atttcataaa agttattgta ctatcgatgt caacacattc tacatttttt aatcgtctat 18780
atagtatttt tctgatattt tctataatat cagaattgtc ttccatcgga agttgtatac 18840
tatcggaatc agttacatgt ttaaataatt ctctgatgtc attccttata caatcaaatt 18900
cattattaaa cagtttaata gtctgtagac ctttatcgtc gtaaatatcc attgtcttat 18960
tagttacgct tatttttatg tgttttacat tgctttatta tattttataa gaatgattgt 19020
ttgacgaatc acgagaacta ttaagacaca ttattaggta tatattataa aaaagttttt 19080
gattacgatg ttataagagg aaagaggaca cattaacatc atacatcaat taactacatt 19140
cttataacat cgtaatcaaa agaattgcaa ttttgatgta taacaactgt caatgggtta 19200
tggaattgta tattacatat tatacggtat gttggtaacg acaaataccg gtcggtaatt 19260
gtctgccggt gtaatagaat tatatatata tctatctatt acaccggcct tgtatacata 19320
ataataagtt gtggtagtat gatctccata tttataattt aggactttgt attcagtatt 19380
tttggaatca taaaaaataa aaaaaagttt tactaattta aaatttaaaa agtatttaca 19440
tttttttcac tgtttagtcg cggatatgga attcgatcct gccaaaatca atacatcatc 19500
tatagatcat gtaacaatat tacaatacat agatgaacca aatgatataa gactaacagt 19560
atgcattatc cgaaatatta ataacattac atattatatc aatatcacaa aaataaatac 19620
acatttggct aatcaatttc gggcttggaa aaaacgtatc gccggaaggg actatataac 19680
taacttatct agagatacag gaatacaaca atcaaaactt actgaaacta tacgtaactg 19740
tcaaaaaaat agaaacatat atggtctata tatacactac aatttagtta ttaatgtggt 19800
tattgattgg ataaccgatg tgattgttca atcaatatta agagggttgg taaattggta 19860
catagctaat aatacctata cacccaataa tacaacaacc atttctgagt tggatatcat 19920
caaaatactg gataaatacg aggacgtgta tagagtaagt aaagaaaaag aatgtggaat 19980
ttgctatgaa gttgtttact caaaacgatt agaaaacgat agatactttg gtttattgga 20040
ttcgtgtaat catatatttt gcataacatg tatcaatata tggcataaaa cacgaagaga 20100
aaccggtgcg tcggataatt gtcctatatg tcgtacccgt tttagaaaca taacaatgag 20160
caagttctat aagctagtta actaataaat aaaaagttta atttgttgac gacgtatgtc 20220
gttatttttt ctcgtataaa agattaaatt caattcaatt cgttgtttct aatataatct 20280
gccgtattgg atggattctc aagacaattg catttagatt atattatcat gaataaaaat 20340
agtagcacac aactacttca gcaaatattc ttttttgaaa cgccatctat cgtagtgagg 20400
acacaagtga acctataatt atcaaattta ttagtatcag tcacatgaag gactttctgt 20460
agagtgacga ttccactatc tgtggtacga acggtttcat cttctttgat gccatcaccc 20520
agatgttcta taaacttggt atcctcgtcc gatttcatat cctttgccaa ccaatacata 20580
tagctaaact caggcatatg ttccacacat cctgaacaat gaaattctcc agaagatgtt 20640
acaatgtcta gatttggaca tttggtttca accgcgttaa catatgagtg aacacaccca 20700
tacatgaaag cgatgagaaa taggattctc atcttgccaa aatatcacta gaaaaaattt 20760
atttatcaat tttaaaggta taaaaaatac ttattgttgc tcgaatattt tgtatttgat 20820
ggtatacgga agattagaaa tgtaggtatt atcatcaact gattctatgg ttttatgtat 20880
tctatcatgt ttcactattg cgttggaaat aatatcatat gcttccacat atattttatt 20940
ttgttttaac tcataatact cacgtaattc tggattattg gcatatctat gaataatttt 21000
agctccatga tcagtaaata ttaatgagaa catagtatta ccacctacca ttattttttt 21060
catctcattc aattcttaat tgcaaagatc tatataatca ttatagcgtt gacttatgga 21120
ctctggaatc ttagacgatg tacagtcatc tataatcatg gcatatttaa tacattgttt 21180
tatagcatag tcgttatcta cgatgttaga tatttctctc aatgaatcaa tcacataatc 21240
taatgtaggt ttatgacata atagcatttt cagcagttca atgtttttag attcgttgat 21300
ggcaatggct atacatgtat atccgttatt tgatctaatg ttgacatctg aaccggattc 21360
tagcagtaaa gatactagag attgtttatt atatctaaca gccttgtgaa gaagtgtttc 21420
tcctcgtttg tcaatcatgt taatgtcttt aagataaggt aggcaaatgt ttatagtact 21480
aagaattggg caagcataag acatgtcaca aagacccttt ttgtatgtat aagtgtaaaa 21540
attataacat ccatagttgg atttacatag gtgtccaatc gggatctctc catcatcgag 21600
ataattgatg gcatctccct tcctttttta gtagatattt catcgtgtaa gaatcaatat 21660
taatatttct aaagtatccg tgtatagcct ctttatttac cacagttcca tattccacta 21720
gagggatatc gccgaatgtc atatactcaa ttagtatatg ttggaggaca tccgagttca 21780
ttgttttcaa tatcaaaaag atggtttcct tatcatttct ccatagtggt acaatactac 21840
acattatttc gtgcggcttt ccattttcca aaaacaattt gaccaaatct aaatctacat 21900
ctttattgta tctataatca ctatttagat aatcagccat aattcctcga gtgcaacatg 21960
ttagatcgtc tatatatgaa taagccgtgt tatctattcc tttcattaac aatttaacga 22020
tgtctatatc tatatgagat gacttaatat aatattgaag agctgtacaa tagtttttat 22080
ctataaaaga cggcttgatt ccgtgattaa ttagacattt aacaacttcc ggacgcacat 22140
atgctctcgt atccgacttt gaatacagat gagagatgat atacagatgc aatacggtac 22200
cgcaatttcg tagttgataa tcatcatacg cgtatcagta ctcgtcctca taaagaacac 22260
tgcagccatt ttctatgaac aaatcaataa ttttaggaac aggatcattg tcattacata 22320
attttctata actgaacgat ggttttcaca tttaacactc aagtcaaatc catgttctac 22380
caacaccttt atcaagtcaa cgtctacatt tttggatttc atatagctga atatattaaa 22440
gtcatttatg ttgctaaatc cagtggcttc tagtagagcc atcgctatat cctttaactt 22500
taacatgtct actatttgtg tattcttcta atggggtagc tgtctccaat ttttgcgtaa 22560
tggattagtg ccactgtcta gtagtagttt gacgacctcg acattattac aatgctcatt 22620
aaaaaggtat gcgtgtaaag cattattctt gaattggttc ctggtatcat taggatctct 22680
gtctctcaac atctgtttaa gttcatcgag agccacctcc tcattttcca aatagtcaaa 22740
cattttgact gaatgagcta ctgtgaactc tatacaccca cacaactaat gtcattaaat 22800
atcatgtcaa aaacttgtac aattattaat aaaaataatt tagtgtttaa attttaccag 22860
ttccagattt tacacctccg ttaatacctc cattaacccc actggacgat cctcctcccc 22920
acattccacc gccaccagat gtataagttt tagatccttt attactacca tcatgtccat 22980
ggataaagac actccacatg ccgccactac cccctttaga agacatatta ataagactta 23040
aggacaagtt taacaataaa attaatcacg agtaccctac taccaaccta cactattata 23100
tgattatagt ttctattttt acagtacctt gactaaagtc tctagtcaca agagcaatac 23160
taccaaccta cactattata tgattatagt ttctattttt ataggaacgc gtacgagaaa 23220
atcaaatgtc taatttctaa cggtagtgtt gataaacgat tatcgtcaat ggatacctcc 23280
tctatcatgt cgtctatttt cttactttgt tctattaact tattagcatt atatattatt 23340
tgattataaa acttatattg cttattagcc caatctgtaa atatcggatt attaacatat 23400
cgtttctttg taggtttatt taacatgtac atcactgtaa gcatgtccgt accatttatt 23460
ttaatttgac gcatatccgc aatttctttt tcgcagtcgg ttataaattc tatatatgat 23520
ggatacatgc tacatgtgta cttataatcg actaatatga agtacttgat acatattttc 23580
agtaacgatt tattattacc acctatgaat aagtacctgt gatcgtctag gtaatcaact 23640
gtttttttaa tacattcgat ggttggtaat ttactcagaa taatttccaa tatcttaata 23700
tataattctg ctatttctgg gatatattta tctgccagta taacacaaat agtaatacat 23760
gtaaacccat attttgttat tatattaatg tctgcgccat tatctattaa ccattctact 23820
aggctgacac tatgcgactc aatacaatga taaagtatac tacatccatg tttatctatt 23880
ttgtttatat cattaatata cggcttacaa agttttagta tcgataacac atccaactca 23940
cgcatagaga aggtagggaa taatggcata atatttatta ggttatcatc attgtcatta 24000
tctacaacta agtttccatt ttttaaaata tactcgacaa ctttaggatc tctattgcca 24060
aatttttgaa aatatttatt tatatgctta aatctatata atgtagctcc ttcatcaatc 24120
atacatttaa taacattgat gtatactgta tgataagata catattctaa caatagatct 24180
tgtatagaat ctgtatatct tttaagaatt gtggatatta ggatattatt acgtaaacta 24240
ttacacaatt ctaaaatata aaacgtatca cggtcgaata atagttgatc aactatataa 24300
ttatcgattt tgtgattttt cttcctaaac tgtttacgta aatagttaga tagaatattc 24360
attagttcat gaccactata gttactatcg aataacgcgt caaatatttc ccgtttaata 24420
tcgcatttgt caagataata atagagtgtg gtatgttcac gataagtata ataacgcatc 24480
tctttttcgt gtgaaattaa atagtttatt acgtccaaag atgtagcata accatcttgt 24540
gacctagtaa taatataata atagagaact gttttaccca ttctatcatc ataatcagtg 24600
gtgtagtcgt aatcgtaatc gtctaattca tcatcccaat tataatattc accagcacgt 24660
ctaatctgtt ctattttgat cttgtatcca tactgtatgt tgctacatgt aggtattcct 24720
ttatccaata atagtttaaa cacatctaca ttgggatttg atgttgtagc gtatttttct 24780
acaatattaa taccattttt gatactattt atttctatac ctttcgaaat tagtaatttc 24840
aataagtcta tatcgatgtt atcagaacat agatattcga atatatcaaa atcattgata 24900
tttttatagt cgactgacga caataacaaa atcacgacat cgtttttgat attattattt 24960
ttcttggtaa cgtatgcctt taatggagtt tcaccatcat actcatataa tggatttgca 25020
ccactttcta tcaatgattg tgcactgctg gcatcgatgt taaatgtttt acaactatca 25080
tagagtatct tatcgttaac catgattggt tgttgatgct atcgcatttt ttggtttctt 25140
tcatttcagt tatgtatgga tttagcacgt ttgggaagca tgagctcata tgatttcagt 25200
actgtagtgt cagtactatt agtttcgatc agatcaatgt ctagatctat agaatcaaaa 25260
cacgataggt cagaagataa tgaatatctg tacgcttctt gttgtactgt aacttctggt 25320
tttgttagat ggttgcatcg tgctttaacg tcaatggtac aaattttatc ctcgctttgt 25380
gtatcatatt cgtccctact ataaaattgt atattcagat tatcatgaga tgtgtatacg 25440
ctaacggtat caataaacgg agcacaccat ttagtcataa ccgtaatcca aaaattttta 25500
aagtatatct taacgaaaga agttgtgtca ttgtctacgg tgtatggtac tagatcctca 25560
taagtgtata tatctagagt aatgtttaat ttattaaatg gttgataata tggatcctca 25620
tgacaatttc cgaagatgga aataagacat aaacacgcaa taaatctaat tgcggacatg 25680
gttactcctt aaaaaaatac gaataatcac cttggctatt tagtaagtgt catttaacac 25740
tatactcata ttaatccatg gactcataat ctctatacgg gattaacgga tgttctatat 25800
acggggatga gtagttctct tctttaactt tatacttttt actaatcata tttagactga 25860
tgtatgggta atagtgtttg aagagctcgt tctcatcatc agaataaatc aatatctctg 25920
tttttttgtt atacagatgt attacagcct catatattac gtaatagaac gtgtcatcta 25980
ccttattaac tttcaccgca tagttgtttg caaatacggt taatcctttg acctcgtcga 26040
tttccgacca atctgggcgt ataatgaatc taaactttaa tttcttgtaa tcattcgaaa 26100
taatttttag tttgcatccg tagttatccc ctttatgtaa ctgtaaattt ctcaacgcga 26160
tatctccatt aataatgatg tcgaattcgt gctgtatacc catactgaat ggatgaacga 26220
ataccgacgg cgttaatagt aatttacttt ttcatcttta catattgggt actagtttta 26280
ctatcataag tttataaatt ccacaagcta ctatggaata agccaaccat cttagtataa 26340
cacacatgtc ttaaagttta ttaattaatt acatgttgtt ttatatatat cgctacgaat 26400
ttaaacagag aaatcagttt aggaaaaaaa attatctatc tacatcatca cgtctctgta 26460
ttctacgata gagtgctact ttaagatgcg acagatctgt gtcatcaaat atatactcca 26520
ttaaaatgat tattccggca gcgaacttga tattggatat atcacaacct ttgttaatat 26580
ctacgacaat agacagcagt cccatggttc cataaacagt gagtttatct ttctttgaag 26640
agatattttg tagagatctt ataaaactgt cgaatgacat cgcatttata tctttagcta 26700
aatcgtatat gttaccatcg taatatctaa ccgcgtctat cttaaacgtt tccatcgctt 26760
taaagacgtt tccgatagat ggtctcattt catcagtcat actgagccaa caaatataat 26820
cgtgtataac atctttgata gaatcagact ctaaagaaaa cgaatcggct ttattatacg 26880
cattcatgat aaacttaatg aaaaatgttt ttcgttgttt aagttggatg aatagtatgt 26940
cttaataatt gttattattt cattaattaa tatttagtaa cgagtacact ctataaaaac 27000
gagaatgaca taactagtta tcaaagtgtc taggacgcgt aattttcata tggtatagat 27060
cctgtaagca ttgtctgtat tctggagcta ttttctctat cgcattagtg agttcagaat 27120
atgttataaa tttaaatcga ataacgaaca taactttagt aaagtcgtct atattaactc 27180
ttttattttc tagccatcgt aataccatgt ttaagatagt atattctcta gttactacga 27240
tctcatcgtt gtctagaata tcacatactg aatctacatc caattttaga aattggtctg 27300
tgttacatat ctcttctata ttattgttga tgtattgtcg tagaaaacta ttacgtagac 27360
cattttcttt ataaaacgaa tatatagtac tccaattatc tttaccgata tatttgcaca 27420
cataatccat tctctcaatc actacatctt taagattttc gttgttaaga tatttggcta 27480
aactatataa ttctattaga tcatcaacag aatcagtata tatttttcta gatccaaaga 27540
cgaactcttt ggcgtcctct ataatattcc cagaaaagat attttcgtgt tttagtttat 27600
cgagatctga tctgttcata tacgccatga ttgtacggta cgttatgata accgcataaa 27660
ataaaaatcc attttcattt ttaaccaata ctattcataa ttgagattga tgtaatactt 27720
tgttactttg aacgtaaaaa cagtacacgg atccgtatct ccaacaagca cgtagtaatc 27780
aaatttggtg ttgttaaact tcgcaatatt catcaattta gatagaaact tatactcatc 27840
atctgtttta ggaatccatg tattattacc actttccaac ttatcattat cccaggctat 27900
gtttcgtcca tcatcgttgc gcagagtgaa taattctttt gtattcggta gttcaaatat 27960
atgatccatg catagatcag taaagctatt gtagatgtga tttttcctaa atctaatata 28020
aaactcgttt actagcaaac actttcctga tttatcgacc aagacacata tggtttctaa 28080
atctatcaag tggtggggat ccatagttat gacgcagtaa catatattat tacattcttg 28140
actgtcgcta atatctaaat atttattgtt atcgtattgg attctgcata tagatggctt 28200
gtatgtcaaa gatatagaac acataaccaa tttatagtcg cgctttacat tctcgaatct 28260
aaagttaaga gatttagaaa acattatatc ctcggatgat gttatcactg tttctggagt 28320
aggatatatt aaagtcttta cagatttcgt ccgattcaaa taaatcacta aataatatcc 28380
cacattatca tctgttagag tagtatcatt aaatctatta tattttatga aagatatatc 28440
actgctcacc tctatatttc gtacattttt aaactgtttg tataatatct ctctgataca 28500
atcagatata tctattgtgt cggtagacga taccgttaca tttgaattaa tggtgttcca 28560
ttttacaact tttaacaagt tgaccaattc atttctaata gtatcaaact ctccatgatt 28620
aaatatttta atagtatcca ttttatatca ctacggacac aaagtagctg acataaacca 28680
ttgtataatt tttatgtttt atgtttatta gcgtacacat tttggaagtt ccggcttcca 28740
tgtatttcct ggagagcaag tagatgatga ggaaccagat agtttatatc cgtacttgca 28800
cttaaagtct acattgtcgt tgtatgagta tgatctttta aacccgctag acaagtatcc 28860
gtttgatatt gtaggatgtg gacatttaac aatctgacac gtgggtggat cggaccattc 28920
tcctcctgaa cacaggacac tagagttacc aatcaacgaa tatccactat tgcaactata 28980
agttacaacg ctcccatcgg tataaaaatc ctcgtatccg ttatgtcttc cgttggatat 29040
agatggaggg gattggcatt taacagattc acaaataggt gcctcgggat tccataccat 29100
agatccagta gatcctaatt cacaatacga tttagattca ccgatcaaat gatatccgct 29160
attacaagag tacgttatac tagagccaaa gtctactcca ccaatatcaa gttggccatt 29220
atcgatatct cgaggcgatg ggcatctccg tttaatacat tgattaaaga gtgtccatcc 29280
agtacctgta catttagcat atataggtcc cattttttgc tttctgtatc caggtagaca 29340
tagatattct atagtgtctc ctatgttgta attagcatta gcatcagtct ccacactatt 29400
cttaaatttc atattaatgg gtcgtgacgg aatagtacag catgatagaa cgcatcctat 29460
tcccaacaat gtcaggaacg tcacgctctc caccttcata tttatttatc cgtaaaaatg 29520
ttatcctgga catcgtacaa ataataaaaa gcccatatat gttcgctatt gtagaaattg 29580
tttttcacag ttgctcaaaa acgatggcag tgacttatga gttacgttac actttggagt 29640
ctcatcttta gtaaacatat cataatattc gatattacga gttgacatat cgaacaaatt 29700
ccaagtattt gattttggat aatattcgta ttttgcatct gctataatta agatataatc 29760
accgcaagaa cacacgaaca tctttcctac atggttaaag tacatgtaca attctatcca 29820
tttgtcttcc ttaactatat atttgtatag ataattacga gtctcgtgag taattccagt 29880
aattacatag atgtcgccgt cgtactctac agcataaact atactatgat gtctaggcat 29940
gggagacttt tttatccaac gatttttagt gaaacattcc acatcgttta atactacata 30000
tttttcatac gtggtataaa ctccacccat tacatatata tcatcgttta cgaataccga 30060
cgcgcctgaa tatctaggag taattaagtt tggaagtctt atccatttcg aagtgccgtg 30120
tttcaaatat tctgccacac ccgttgaaat agaaaattct aatcctccta ttacatataa 30180
ctttccatcg ttaacacaag tactaacttc tgattttaac gacgacatat tagtaaccgt 30240
tttccatttt ttcgtttcaa gatctacccg cgatacggaa taaacatgtc tattgttaat 30300
catgccgcca ataatgtata gacaattatg taaaacattt gcattataga attgtctatc 30360
tgtattaccg actatcgtcc aatattctgt tctaggagag taatgggtta ttgtggatat 30420
ataatcagag tttttaatga ctactatatt atgttttata ccatttcgtg tcactggctt 30480
tgtagatttg gatatagtta atcccaacaa tgatatagca ttgcgcatag tattagtcat 30540
aaacttggga tgtaaaatgt tgatgatatc tacatcgttt ggatttttat gtatccactt 30600
taataatatc atagctgtaa catcctcatg atttacgtta acgtcttcgt gggataagat 30660
agttgtcagt tcatcctttg ataattttcc aaattctgga tcggatgtca ccgcagtaat 30720
attgttgatt atttctgaca tcgacgcatt atatagtttt ttaattccat atcttttaga 30780
aaagttaaac atccttatac aatttgtgaa attaatatta tgaatcatag tttttacaca 30840
tagatctact acaggcggaa catcaattat tacggcagca actagtatca tttctacatt 30900
gtttatggtg atgtttatct tcttccagcg catatagtct aatagcgatt caaacgcgtg 30960
atagtttata ccattcaata taatcgcttc atcctttaga tggtgatcct gaatgcgttt 31020
aaaaaaatta tacggagacg ccgtaataat ttccttattc acttgtataa tttccccatt 31080
gatagaaaat atcacgcttt ccattcttaa agtactataa gtaattatag tataatgtaa 31140
acgtttatat attcaatatt tttataaaaa tcattttgac attaattcct ttttaaattt 31200
ccgtctatca tctatagaaa cgtattctat gaatttataa aatgctttta cgtgtcctat 31260
cgtaggcgat agaaccgcta aaaagcctat cgaatttcta caaaagaatc tgttatatgg 31320
tatagggaga gtataaaaca ttaaatgtcc gtacttatta aagtattcag tagccaatcc 31380
taactctttc gaatacttat taatggctct tgttctgtac gaatctattt ttttgaacaa 31440
cggacctagt ggtatatctt gttctatgta tctaaaataa tgtctgacta gatccgttag 31500
tttaatatcc tcagtcatct tgtctagaat ggcaaatcta actgcgggtt taggctttag 31560
tttagtttct atatctacat ctatgtcttt atctaacacc aaaaatataa tagctaatat 31620
tttattacaa tcatccggat attcttctac gatctcacta actaatgttt ctttggttat 31680
actagtatag tcactatcgg acaaataaag aaaatcagat gatcgatgaa taatacattt 31740
aaattcatca tctgtaagat ttttgagatg tctcattaga atattattag ggttagtact 31800
cattatcatt aggcagctat tacttatttt attatttttc accatataga tcaatcatta 31860
gatcatcaaa atatgtttca atcatcctaa agagtatggt gaatgactct tcccatctaa 31920
tttctgaacg ttcaccaatg tctctagcca ctttggcact aatagcgatc attcgcttag 31980
cgtcttctat attattaact ggttgattca atctatctag caatggaccg tcggacagcg 32040
tcattctcat gttcttaatc aatgtacata catcgccgtc atctaccaat tcatccaaca 32100
acataagctt tttaaaatca tcattataat aggtttgatc gttgtcattt ctccaaagaa 32160
tatatctaat aagtagagtc ctcatgctta gtaatttaac tattttagtt aacaactatt 32220
ttttatgtta aatcaattag tacaccgcta tgtttaatac ttattcatat tttagttttt 32280
aggattgaga atcaatacaa aaattaatgc atcattaatt ttagaaatac ttagtttcca 32340
cgtagtcaat gaaacatttg aactcatcgt acaggacgtt ctcgtacagg acgtaactat 32400
aaaccggttt atatttgttc aagatagata caaatccgat aacttttttt acgaattcta 32460
cgggatccac tttaaaagtg tcataccggg ttctttttat ttttttaaac agatcaatgg 32520
tgtgatgttg attaggtctt ttacaaattt gatatagaat agcgtttaca tattctccat 32580
aatggtcaat cgccatttgt tcgtatgtca taaattcttt aattatatga cactgtgtat 32640
tatttagttc atccttgttc attgttagga atctatccaa aatggcaatt atactagaac 32700
tataggtgcg ttgtatacac atattgatgt gtctgtttat acaatccatg atatttggat 32760
ccatgctact accttcgggt aaaattgtag catcatatac catttctagt actttaggtt 32820
cattattatc cattgcagag gacgtcatga tcgaatcata aaaaaatata ttatttttat 32880
gttattttgt taaaaataat catcgaatac ttcgtaagat actccttcat gaacataatc 32940
agttacaaaa cgtttatatg aagtaaagta tctacgattt ttacaaaagt ccggatgcat 33000
aagtacaaag tacgcgataa acggaataat aatagattta tctagtctat ctttttctat 33060
agctttcata gttagataca tggtctcaga agtaggatta tgtaacatca gcttcgataa 33120
aatgactggg ttatttagtc ttacacattc gctcatacat gtatgaccgt taactacaga 33180
gtctacacta aaatgattga acaatagata gtctaccatt gtttcgtatt cagatagtac 33240
agcgtagtac atggcatctt cacaaattat atcattgtct aatagatatt tgacgcatct 33300
tatggatccc acttcaacag ccatcttaaa atcggtagaa tcatattgct ttcctttatc 33360
attaataatt tctagaacat catctctatc ataaaagata caaatattaa ctgtttgatc 33420
cgtaataaca ttgctagtcg atagcaattt gttaataaga tgcgctgggc tcaatgtctt 33480
aataagaagt gtaagaggac tatctccgaa tttgttttgt ttattaacat ccgttgatgg 33540
aagtaaaaga tctataatgt ctacattctt gactgtttta gagcatacaa tatggagagg 33600
tgtatttcca tcatgatctg gttttgaggg actaattcct agtttcatca tccatgagat 33660
tgtagaagct tttggattgt ctgacataag atgtctatga atatgatttt tgccaaattt 33720
atccactatc ctggcttcga atccgatgga cattattttt ttaaacactc tttctgaagg 33780
atctgtacac gccaacaacg gaccacatcc ttcttcatca accgagttgt taatcttggc 33840
tccatactgt accaataaat ttattctctc tatgacttca tcatctgttc ccgagagata 33900
atatagaggc gttttatgct gtttatcaca cgcgtttgga tctgcgccgt gcgtcagcag 33960
catcgcgact attctattat tattaatttt agaagctata tgcaatggat aatttccatc 34020
atcatccgtc tcatttggag agtatcctct atgaagaagt tcttcgacaa atcgttcatc 34080
tagtccttta attccacaat acgcatgtag aatgtgataa ttatttccag aaggttcgat 34140
agcttgtagc atattcctaa atacatctaa atttttacta ttatatttgg cataaagaga 34200
tagataatac tcggccgaca taatgttgtc cattgtagta taaaaattaa tatttctatt 34260
tctatttctg tatatttgca acaatttact ctctataaca aatatcataa cttagttctt 34320
ttatgtcaag aaggcactgg tttagttcat ctataaatgt cacgccataa ctaccacgca 34380
tgccatactc agaattatga taaagatatt tatccttggg gtgtaggtaa tggggattaa 34440
tctttgttgg atcagtctct aagttaacac atgtcacaca tgatccattt atagttatat 34500
cacacgatga tgatttatga attgattccg gaagatcgct atcgtatttt gtggttccac 34560
aattcatttc catacatgtt attgtcacac taatattatg atgaacttta tctagccgct 34620
gagtggtaaa caacagaaca gatagtttat tatctttacc aacaccctca gccgctgcca 34680
caaatctctg atccgtatcc atgatggtca tgtttatttc tagtccgtat ccagtcaaca 34740
ctatgttagc atttctgtcg atatagcttt cactcatatg acactcacca ataatagtag 34800
aattaatgtc gtaatttaca ccaatagtga gttcggcggc aaagtaccaa taccggtaat 34860
cttgtcgagg aggacatata gtattcttgt attctaccga atacccgaga gatgcgatac 34920
aaaagagtaa gactaatttg taaaccatct tactcaaaat atgtaacaat agtacgatgc 34980
aatgagtaag acaataggaa atctatctta tatacacata attattctat caattttacc 35040
aattagttag tgtaatgtta acaaaaatgt gggagaatct aattagtttt tctttacaca 35100
attgacgtac atgagtttga gttccttgtt tttgctaatt atttcatcca atttattatt 35160
cttgacgata tcgagatctt ttgtatagga gtcagacttg tattcaacat gcttttctat 35220
aatcatttta gctatttcgg catcatccaa tagtacattt tccagattag cagaatagat 35280
attaatgtcg tatttgaaca gagcctgtaa catctcaatg tctttattat ctatagccaa 35340
tttaatgtcc ggaatgaaga gaagggaatt attggtgttt gtcgacgtca tatagtcgag 35400
caagagaatc atcatatcca cgtgtccatt ttttatagtg atgtgaatac aactaaggag 35460
aatagccaga tcaaaagtag atggtatctc tgaaagaaag taggaaacaa tacttacatc 35520
attaagcatg acggcatgat aaaatgaagt tttccatcca gttttcccat agaacatcag 35580
tctccaattt ttcttaacaa acagttttac cgtttgcatg ttaccactat caaccgcata 35640
atacaatgca gtgtttccct tgtcatcaaa ttgtgaatca tccagtccac tgaatagcaa 35700
aatctttact attttagtat cttccaatgt ggctgcctga tgtaatggaa attcattctc 35760
tagaagattt ttcaatgctc cagcgttcaa caacgtacat actagacgca cgttattatc 35820
agctattgca taatacaagg cactatgacc gttgatatcc gccttaaatg catctttgct 35880
agagagaaag cttttcagct gcttagactt ccaagtatta attcgtgaca gatccatgtc 35940
tgaaacaaga cgctaattag tgtatatttt ttcatttttt ataattttgt catattgcac 36000
cagaattaat aatatctcta atagatctga ttagtagata catggctatc gcaaaacaac 36060
atatacacat ttaataaaaa taatatttat taagaaaatt cagatttcac gtacccatca 36120
atataaataa aataatgatt ccttacaccg tacccatatt aaggagattc caccttaccc 36180
ataaacaata taaatccagt aatatcatgt ctgatgatga acacaaatgg tgtattaaat 36240
tccagttttt caggagatga tctcgccgta gctaccataa tagtagatgc ctctgctaca 36300
gttccttgtt cgtcgacatc tatctttgca ttctgaaaca ttttataaat atataatggg 36360
tccctagtca tatgtttaaa cgacgcatta tctggattaa acatactagg agccatcatt 36420
tcggctatcg acttaatatc cctcttattt tcgatagaaa atttagggag tttaagattg 36480
tacactttat tccctaattg aaacgaccaa tagtctaatt ttgcagccgt gatagaatct 36540
gtgaaatggg tcatattatc acctattgcc aggtacatac taatattagc atccttatac 36600
ggaaggcgta ccatgtcata ttctttgtca tcgattgtga ttgtatttcc ttgcaattta 36660
gtaactacgt tcatcatggg aaccgttttc gtaccgtact tattagtaaa actagcattg 36720
cgtgttttag tgatatcaaa cggatattgc catatacctt taaaatatat agtattaatg 36780
attgcccata gagtattatt gtcgagcata ttagaatcta ctacattaga cataccggat 36840
ctacgttcta ctatagaatt aattttatta accgcatctc gtctaaagtt taatctatat 36900
aggccgaatc tatgatattg ttgataatac gacggtttaa tacacacagt attatctacg 36960
aaactttgat aagttagatc agtgtacgta tatttagatg ttttcagctt agctaatcct 37020
gatattaatt ctgtaaatgc tggacccaga tctctttttc tcaaatccat agtcttcaat 37080
aattctattc tagtattacc tgatgcaggc aatagcgaca taaacataga aaacgaataa 37140
ccaaacggtg agaagacaat attatcatct tgaatatttt tatacgctac tataccggca 37200
ttggtaaatc cttgtagacg ataggcggac gctgaacacg ctaacgatag tatcaataac 37260
gcaatcatga ttttatggta ttaataatta accttatttt tatgttcggt ataaaaaaat 37320
tattgatgtc tacacatcct tttgtaattg acatctatat atccttttgt ataatcaact 37380
ctaatcactt taacttttac agttttccct accagtttat ccctatattc aacatatcta 37440
tccatatgca tcttaacact ctctgccaag atagcttcag agtgaggata gtcaaaaaga 37500
taaatatata gagcataatc attctcgtat actctgccct ttattacatc acccgcattg 37560
ggcaacgaat aacaaaatgc aagcatcttg ttaacgggct cgtaaattgg gataaaaatt 37620
atgtttttat tgtcttatat ctattttatt caagagaata ttcaggaatt tctttttccg 37680
gttgtatctc atcgcagtat atatcatttg tacattgttt tatatttttt aatagtttac 37740
accttttagt aggactagta tcgtacaatt catagctgta ttttgaattc caatcacgca 37800
taaaaatatc ttccaattgt tgacgaagac ctaatccatc atccggtgta atattaatag 37860
atgctccaca tgtatccgta aagtaatttc ctgtccaatt tgaggtacct atataggccg 37920
ttttatcggt taccatatat ttggcatggt ttaccctaga atacggaatg ggaggatcag 37980
catctggtac aataaatagc tttacttcta tatttatgtt tttagatttt agcatagcga 38040
tagatcttaa aaagtttctc atgataaacg aagatcgttg ccagcaacta atcaatagct 38100
taacggatac ttgtctgtct atagcggatc ttcttaattc atcttctata taaggccaaa 38160
acaaaatttt acccgccttc gaataaataa tagggataaa gttcataaca gatacataaa 38220
cgaatttact cgcatttcta atacatgaca ataaagcggt taaatcattg gttctttcca 38280
tagtacatag ttgttgcggc gcagaagcaa taaatacaga gtgtggaacg ccgcttacgt 38340
taatactaag aggatgatct gtattataat acgacggata aaagtttttc caattatatg 38400
gtagattgtt aactccaaga taccagtata cctcaaaaat ttgagtgaga tccgctgcca 38460
agttcctatt attgaagatc gcaataccca attctttgac ctgagttagt gatctccaat 38520
ccatgttagc gcttcctaaa taaatatgtg tattatcaga tatccaaaat tttgtatgaa 38580
gaactcctcc taggatattt gtaatatcta tgtatcgtac ttcaactccg gccatttgta 38640
gtctttcaac atcctttaat ggtttgttag atttattgac ggctactcta actcgtactc 38700
ctcttttggg taattgtaca atctcgttta atattatcgt gccgaaattc gtacccactt 38760
catccgataa actccaataa aaagatgata tatctagtgt ttttgtggta ttggatagaa 38820
tttccctcca catgttaaat gtagacaaat atactttatc aaattgcata cctataggaa 38880
tagtctctgt aatcactgcg attgtattat ccggattcat tttatttgtt aaaaaataat 38940
cctatatcac ttcactctat taaaaatcca agtttctatt tctttcatga ctgatttttt 39000
aacttcatcc gtttccttat gaagatgatg tttggcacct tcataaattt ttatttctct 39060
attacaattt gcatgttgca tgaaataata tgcacctaaa acatcgctaa tcttattgtt 39120
tgttccctgg agtatgagag tcggggggtg ttaatcttgg aaattatttt tctaaccttg 39180
ttggtagcct tcaagacctg actagcaaat ccagccttaa ttttttcatg attgactaat 39240
gggtcgtatt ggtatttata aacttcatcc atatctctag atactgattc tggacatagc 39300
tttccgactg gcgcatttgg tgtgatggtt cccataagtt tggcagctag cagattcagt 39360
cttgaaacag catctgcatt aactagagga gacattagaa tcattgctgt aaacaagttt 39420
ggattatcgt aagaggctag ctcccatgga atgacccaat aagtagattt aatagttacc 39480
acgtgctgta ccaaagtcat caatcatcat tttttcacca ttacttcttc catgtccaat 39540
atgatcatgt gagaatacta aaattcctaa cgatgatatg ttttcagcta gttcgtcata 39600
acgtccagaa tgtttaccag ctccatgact tataaatact aatgccttag gatatgtaat 39660
aggtttccaa tatttacaat atatgtaatc attgtccaga ttgaacatac agtttgcact 39720
catgattcac gttatataac tatcaatatt aacagttcgt ttgatgatca tattattttt 39780
atgttttatt gataattgta aaaacataca attaaatcaa tatagaggaa ggagacggct 39840
actgtctttt gtgagatagt catggcgact aaattagatt atgaggatgc tgttttttac 39900
tttgtggatg atgataaaat atgtagtcgc gactccatca tcgatctaat agatgaatat 39960
attacgtgga gaaatcatgt tatagtgttt aacaaagata ttaccagttg tggaagactg 40020
tacaaggaat tgatgaagtt cgatgatgtc gctatacggt actatggtat tgataaaatt 40080
aatgagattg tcgaagctat gagcgaagga gaccactaca tcaattttac aaaagtccat 40140
gatcaggaaa gtttattcgc taccatagga atatgtgcta aaatcactga acattgggga 40200
tacaaaaaga tttcagaatc tagattccaa tcattgggaa acattacaga tctgatgacc 40260
gacgataata taaacatctt gatacttttt ctagaaaaaa aattgaattg atgatatagg 40320
ggtcttcata acgcataatt attacgttag cattctatat ccgtgttaaa aaaaattatc 40380
ctatcatgta tttgagagtt ttatatgtag caaacatgat agctgtgatg ccaataagct 40440
ttagatattc acgcgtgcta gtgttaggga tggtattatc tggtggtgaa atgtccgtta 40500
tataatctac aaaacaatca tcgcatatag tatgcgatag tagagtaaac atttttatag 40560
tttttactgg attcatacat cgtctaccca attcggttat aaatgaaatt gtcgccaatc 40620
ttacacccaa ccccttgtta tccattagta tagtattaac ttcgttattt atgtcataaa 40680
ctgtaaatga ttttgtagat gccatatcat acatgatatt catgtcccta ttataatcat 40740
tactaacttt atcacaatat atgttgataa tatctatata tgatctagtc tttgtgggca 40800
actgtctata caagtcgtct aaacgttgtt tactcatata gtatcgaaca gccatcatta 40860
catggtcccg tttcgttgat agataatcga gtatgttagt ggacttgtca aatctatata 40920
ccatattttc tggaagtgga tatacatagt cgtgatcaac attattgcta gcctcatctt 40980
ctatatcctg tactatacca ttatctatat catctacata atctacgata ttattacaca 41040
taaacatcga caacatacta ttgtttatta tctaagtcct gttgatccaa acccttgatc 41100
tcctctattt gtactatcta gagattgtac ttcttccagt tctggataat atatacgttg 41160
atagattagc tgagctattc tatctccagt atttacatta aacgtacatt ttccattatt 41220
aataagaatg actcctatgt ttcccctata atcttcgtct attacaccac ctcctatatc 41280
aatgcctttt agtgacagac cagacctagg agctattcta ccatagcaaa tcttaggcat 41340
ggacatacta atatctgtct taattaactg tctttctcct ggagggatag tataatcgta 41400
agcgctatac aaatcatatc cggcagcacc cggcgattgc ctagtaggag atttagctct 41460
gttagtttcc ttaacaaatc taactggtga gttaatattc atgttgaaca taaaactaat 41520
attttatttc aaaattattt accatcccat atattccatg aataagtgtg atgattgtac 41580
acttctatag tatctatata cgattcacga taaaatcctc ctatcaatag cagtttatta 41640
tccactatga tcaattctgg attatccctc ggataaatag gatcatctat cagagtccat 41700
gtattgctgg attcacaata aaattccgca tttctaccaa ccaagaataa ccttctaccg 41760
aacactaacg cgcatgattt ataatgagga taataagtgg atggtccaaa ctgccactga 41820
tcatgattgg gtagcaaata ttctgtagtt gtatcagttt cagaatgtcc tcccattacg 41880
tatataacat tgtttataga tgccactgct ggattacatc taggtttcag aagactcggc 41940
atattaaccc aagcagcatc cccgtggaac caacgctcaa cagatgtggg atttggtaga 42000
cctcctacta cgtataattt attgttagcg ggtatcccgc tagcatacag tctggggcta 42060
ttcatcggag gaattggaat ccaattgttt gatatataat ttacagctat agcattgtta 42120
tgtatttcat tgttcatcca tccaccgatg agatatacta cttctccaac atgagtactt 42180
gtacacatat ggaatatatc tataatttga tccatgttca taggatactc tatgaatgga 42240
tacttgtatg atttgcgtgg ttgtttatca caatgaaata ttttggtaca gtctagtatc 42300
cattttacat tatttatacc tctgggagaa agataatttg acctgattac atttttgata 42360
aggagtagca gatttcctaa tttatttctt cgcctcatat accacttaat gacaaaatca 42420
actacataat cctcatctgg aacatttagt tcatcgcttt ctagaataag tttcatagat 42480
agataatcaa aattgtctat gatgtcatct tccagttcca aaaagtgttt ggcaataaag 42540
tttttagtat gacataagag attggatagt ccgtattcta tacccatcat gtaacactcg 42600
acacaatatt cctttctaaa atctcgtaag ataaagttta tacaagtgta gatgataaat 42660
tctacagagg ttaatataga agcacgtaat aaattgacga cgttatgact atctatatat 42720
acctttccag tatatgagta aataactata gaagttaaac tgtgaatgtc aaggtctaga 42780
caaaccctcg taactggatc tttatttttc gtgtattttt gacgtaaatg tgtgcgaaag 42840
taaggagata actttttcaa tatcgtagaa ttgactatta tattgcctcc tatggcatca 42900
ataattgttt tgaatttctt agtcatagac aatgctaata tattcttaca gtacacagta 42960
ttgacaaata tcggcattta tgtttcttta aaagtcaaca tctagagaaa aatgattatc 43020
tttttgagac ataactccca ttttttggta ttcacccaca cgtttttcga aaaaattagt 43080
ttttccttcc aatgatatat tttccatgaa atcaaacgga ttggtaacat tataaatttt 43140
tttaaatccc aattcagaaa tcaatctatc cgcgacgaat tctatatatg ttttcatcat 43200
ttcacaattc attcctataa gtttaactgg aagagccgca gtaagaaatt cttgttcaat 43260
ggatactgca tctgttataa tagatctaac ggtttcttca ctcggtggat gcaataaatg 43320
tttaaacatc aaacatgcga aatcgcagtg cagaccctcg tctctactaa ttagttcgtt 43380
ggaaaacgtg agtccgggca ttaggccacg ctttttaagc caaaatatgg aagcgaatga 43440
tccggaaaag aagattcctt ctactgcagc aaaggcaata agtctctctc cataaccggc 43500
gctgtcatgt atccactttt gagcccaatc ggccttcttt tttacacaag gcatcgtttc 43560
tatggcatta aagagatagt ttttttcatt actatcttta acataagtat cgatcaaaag 43620
actatacatt tccgaatgaa tgttttcaat ggccatctga aatccgtaga aacatctagc 43680
ctcggtaatc tgtacttctg tacaaaatcg ttccgccaaa ttttcattca ctattccgtc 43740
actggctgca aaaaacgcca atacatgttt tataaaatat ttttcgtctg gtgttagttt 43800
attccaatca ttgatatctt tagatatatc tacttcttcc actgtccaaa atgatgcctc 43860
tgccttttta tacatgttcc agatgtcatg atattggatt gggaaaataa caaatctatt 43920
tggatttggt gcaaggatgg gttccataac taaattaaca ataacaataa attttttttc 43980
agttatctat atgcctgtac ttggatcttt tgtacatcga tatcgccgca atcactacaa 44040
taattacaag tattattgat agcattgtta ttagtactat cataattaaa ttatctacat 44100
tcatgggtgc tgaataatcg ttattatcat cattatcatt ttgtaattgt gacatcatac 44160
tagataaatc gtttgcgaga ttgttgtggg aagcgggcat ggaggatgca ttatcattat 44220
tatttaacgc cttccatttg gattcacaaa tgttacgcac attcaacatt ttatggaaac 44280
tataattttg tgaaaacaga taacaagaaa actcgtcatc gttcaaattt ttaacgatag 44340
taaaccgatt aaacgtcgag ctaatttcta acgctagcga ctctgttgga tatgggtttc 44400
cagatatata tcttttcagt tcccctacgt atctataatc atctgtagga aatggaagat 44460
atttccattt atctactgtt cctaatatca tatgtggtgg tgtagtagaa ccattaagcg 44520
cgaaagatgt tatttcgcat cgtattttaa cttcgcaata atttctggtt agataacgca 44580
ctctaccagt caagtcaatg atattagcct ttacagatat attcatagta gtcgtaacga 44640
tgactccatc ttttagatgc gatactcctt tgtatgtacc agaatcttcg tacctcaaac 44700
tcgatatatt taaacaagtt aatgagatat taacgcgttt tatgaatgat gatatataac 44760
cagaagtttt atcctcggtg gctagcgcta taaccttatc attataatac caactagtgt 44820
gattaatatg tgacacgtca gtgtgggtac aaatatgtac attatcgtct acgtcgtatt 44880
cgatacatcc gcatacagcc aacaaatata aaatgacaaa tactctaacg acgttcgtac 44940
ccatcttgat gcggtttaat aaatgttttg atttcaattt attgtaaaaa aagattcggt 45000
tttatactgt tcgatattct cattgcttat attttcatct atcatctcca cacagtcaaa 45060
tccgtggtta gcatgcacct catcaaccgg taaaagacta tcggactctt ctatcattat 45120
aactctagaa tatttaattt ggtcattatt aatcaagtca attatcttat ttttaacaaa 45180
cgtgagtatt ttactcattt tttataaaaa cttttagaaa tatacagact ctatcgtgtg 45240
tctatatctt ctttttatat ccaatgtatt tatgtctgat ttttcttcat ttatcatata 45300
taatggtcca aattctacac gtgcttcgga ttcatccaga tcattaaggt tcttataatt 45360
gtaacatcct tctcttccct cttctacatc ttccttctta ttcttattct tagcgtcaca 45420
gaatctacca cagcaggatc ccatgacgag cgtcatatta aactaatcca ttttcaatta 45480
taatatatga ttagtaatga ccattaaaat aaaaaatatt cttcataacc ggcaagaaag 45540
tgaaaagttc acattgaaac tatgtcagta gtatacatca tgaaatgaga tgaaatgaga 45600
tgaaatgatg atatatatac tctattttgg tggaggatta tatgatataa ttcgtggata 45660
atcattttta agacacattt ctttattcgt aaatcttttc acgttaaatg agtgtccata 45720
ttttgcaatt tcttcatatg atggcggtgt acgtggacga ggctgctcct gttcttgttg 45780
tagtcgccga ctgtcgtgtc tgcgtttaga tccctccatt atcgcgattg cgtagatgga 45840
gtactattat ataccttgta attaaatttt tttattaatt aaacgtataa aaacgttccg 45900
tatctgtatt taagagccag atttcgtcta atagaacaaa tagctacagt aaaaataact 45960
agaataattg ctacacccac tagaaaccac ggatcgtaat acggcaatcg gttttcgata 46020
ataggtggaa cgtatatttt atttaaggac ttaacaattg tctgtaaacc acaatttgct 46080
tccgcggatc ctgtattaac tatctgtaaa agcatatgtt gaccgggcgg agccgaacat 46140
tctccgatat ctaatttctg tatatctata atattattaa cctccgcata cgcattacag 46200
ttcttttcta gcttggatac cgcactaggt acatcgtcta gatctattcc tatttcctca 46260
gcgatagctc ttctatcctt ttccggaagc aatgaaatca cttcaataaa tgattcaacc 46320
atgagtgtga aactaagtcg agaattactc atgcatttgt tagttattcg gagcgcgcaa 46380
tttttaaact gtcctataac ctctcctata tgaatagcac aagtgacatt agtagggata 46440
gaatgttgag ctaatttttg taaataacta tctataaaaa gattatacaa agttttaaac 46500
tctttagttt ccgccattta tccagtctga gaaaatgtct ctcataataa atttttccaa 46560
gaaactaatt gggtgaagaa tggaaacctt taatctatat ttatcacagt ctgtcttggt 46620
acacatgatg aattcttcta atgccgtact aaattcgata tctttttcga tttctggata 46680
tgtttttaat aaagtatgaa caaagaaatg gaaatcgtaa taccagttat gttcaacttt 46740
gaaattgttt tttattttct tgttaatgat tccagccact tgggaaaagt caaagtcgtt 46800
taatgccgat ttaatacgtt cattaaaaac aaacttttta tcctttagat gaattattat 46860
tggttcattg gaatcaaaaa gtaagatatt atcgggttta agatctgcgt gtaaaaagtt 46920
gtcgcagcat ggtagttcgt aaattttaat gtataacaga gccatctgta aaaagataaa 46980
ctttatgtat tgtaccaaag atttaaatcc taatttgata gctagctcgg tatctacttt 47040
atctgccgaa tacagtgcta ggggaaaaat tataatgttt cctctttcat attcgtagtt 47100
agttctcttt tcatgttcga aaaagtgaaa catgcggtta aaatagttta taacattaat 47160
attactgtta ataactgccg gataaaagtg ggatagtaat ttcacgaatt tgatactgtc 47220
ctttctctcg ttaaacgcct ttaaaaaaac tttagaagaa tatctcaatg agagttcctg 47280
accatccata gtttgtatca ataatagcaa catatgaaga acccgtttat acagagtatg 47340
taaaaatgtt aatttatagt ttaatcccat ggcccacgca cacacgatta attttttttc 47400
atctcccttt agattgttgt atagaaattt gggtactgtg aactccgccg tagtttccat 47460
gggactatat aattttgtgg cctcgaatac aaattttact acatagttat ctatcttaaa 47520
gactatacca tatcctcctg tagatatgtg ataaaaatcg tcgtttatag gataaaatcg 47580
tttatccttt tgttggaaaa aggatgaatt aatgtaatca ttctcttcta tctttagtag 47640
tgtttcctta ttaaaattct taaaataatt taacaatcta actgacggag cccaattttg 47700
gtgtaaatct aattgggaca ttatattgtt aaaatacaaa cagtctccta atataacagt 47760
atctgataat ctatggggag acatccattg atattcaggg gatgaatcat tggcaacacc 47820
catttattgt acaaaaagcc ccaatttaca aacgaaagtc caggtttgat agagacaaac 47880
aattaactat tttgtctctg tttttaacac ctccacagtt tttaatttct ttagtaatga 47940
aattattcac aatatcagta tcttctttat ctaccagaga ttttactaac ttgataacct 48000
tggctgtctc attcaatagg gtagtaatat ttgtatgtgt gatattgata tctttttgaa 48060
ttgtttcttt tagaagtgat tctttgatgg tgccagcata cgaattacaa taatgcagaa 48120
actcggttaa catgcaggaa ttatagtaag ccaattccaa ttgttgcctg tgttgtatta 48180
gagtgtcaat atgagcaatg gtgtccttgc gtttctctga tagaatgcga gcagcgattt 48240
tggcgttatc atttgacgat atttctggaa tgacgaatcc tgtttctact aactttttgg 48300
taggacaaag tgaaacaatc aagaagatag cttctcctcc tatttgtgga agaaattgaa 48360
ctcctctaga tgatctactg acgatagtat ctccttgaca gatattggac cgaattacag 48420
aagtacctgg aatgtaaagc cctgaaaccc cctcattttt taagcagatt gttgccgtaa 48480
atcctgcact atgcccaaga tagagagctc ctttggtgaa tccatctcta tgtttcagtt 48540
taaccaagaa acagtcagct ggtctaaaat ttccatctct atctaataca gcatctaact 48600
tgatgtcagg aactatgacc ggtttaatgt tatatgtaac attgagtaaa tccttaagtt 48660
cataatcatc actgtcatca gttatgtacg atccaaacaa tgtttctacc ggcatagtgg 48720
atacgaagat gctatccatc agaatgtttc cctgattagt attttctata tagctattct 48780
tctttaaacg attttccaaa tcagtaacta tgttcatttt tttaggagta ggacgcctag 48840
ccagtatgga agaggatttt ctagatcctc tcttcaacat ctttgatctc gatggaatgc 48900
aaaaccccat agtgaaacaa ccaacgataa aaataatatt gtttttcact ttttataatt 48960
ttaccatctg actcatggat tcattaatat ctttataaga gctactaacg tataattctt 49020
tataactgaa ctgagatata tacaccggat ctatggtttc cataattgag taaatgaatg 49080
ctcggcaata actaatggca aatgtataga acaacgaaat tatactagag ttgttaaagt 49140
taatattttc tatgagctgt tccaataaat tatttgttgt aactgcgttc aagtcataaa 49200
tcatcttgat actatccagt aaaccgtttt taagttctgg aatattatca tcccattgta 49260
aagcccctaa ttcgactatc gaatatcctg ctctgatagc agtttcaata tcgacggacg 49320
tcaatactgt aataaaggtg gtagtattgt catcatcgtg ataaactact ggaatatggt 49380
cgttagtagg tacggtaact ttacacaacg cgatatataa ctttcctttt gtaccatttt 49440
taacgtagtt gggacgtcct gcagggtatt gttttgaaga aatgatatcg agaacagatt 49500
tgatacgata tttgttggat tcctgattat tcactataat ataatctaga cagatagatg 49560
attcgataaa tagagaaggt atatcgttgg taggataata catccccatt ccagtattct 49620
cggatactct attgatgaca ctagttaaga acatgtcttc tattctagaa aacgaaaaca 49680
tcctacatgg actcattaaa acttctaacg ctcctgattg tgtctcgaat gcctcgtaca 49740
aggatttcaa ggatgccata gattctttga ccaacgattt agaattgcgt ttagcatctg 49800
atttttttat taaatcgaat ggtcggctct ctggtttgct accccaatga taacaatagt 49860
cttgtaaaga taaaccgcaa gaaaatttat acgcatccat ccaaataacc ctagcaccat 49920
cggatgatat taatgtatta ttatagattt tccatccaca attattgggc cagtatactg 49980
ttagcaacgg tatatcgaat agattactca tgtaacctac tagaatgata gttcgtgtac 50040
tagtcataat atctttaatc caatctaaga aatttaaaat tagatttttt acactgttaa 50100
agttaacaaa agtattaccc ggatacgtgg atatcatata tggcattggt ccattatcag 50160
taatagctcc ataaactgat acggcgatgg tttttatatg tgtttgatct aacgaggaag 50220
aaattcgcgc ccacaattca tctctagata tgtatttaat atcaaacggt aacacatcaa 50280
tttcgggacg cgtatatgtt tctaaatttt taatccaaat ataatgatga cctatatgcc 50340
ctattatcat actgtcaact atagtacacc tagggaactt acgatacatc tgtttcctgt 50400
aatcgttaaa ttttacaaat ctataacatg ctaaaccttt tgacgacaac cattcattaa 50460
tttctgatat ggaatctgta ttctcaatac cgtatcgttc taaagctagt gctatatctc 50520
cctgttcgtg ggaacgcttt cgtataatat cgatcaacgg ataatctgaa gtttttggag 50580
aataatatga ctcatgatct atttcgtcca taaacaatct agacatagga attggaggcg 50640
atgatcttaa ttttgtgcaa tgagtcgtca atcctataac ttctaatctt gtaatattca 50700
tcatcgacat aatactatct atgttatcat cgtatattag tataccacgg ccttcttcat 50760
ttcgtgccaa aatgatatac agtcttaaat agttacgcaa tatctcaata gtttcataat 50820
tgttagctgt tttcatcaag atttgtaccc tgtttaacat gatggcgttc tataacgtct 50880
ctattttcta tttttaattt tttaaatttt taacgattta ctgtggctag atacccaatc 50940
tctctcaaat atttttttag cctcgcttac aagctgttta tctatactat taaaactgac 51000
gaatccgtga ttttggtaat gggttccgtc gaaatttgcc gaagtgatat gaacatattc 51060
gtcgtcgact atcaacaatt ttgtattatt ctgaatagtg aaaaccttca cagatagatc 51120
attttgaaca cacaacgcat ctagactttt ggcggttgcc atagaatata cgtcgttctt 51180
atcccaatta ccaactagaa gtctgatctt aactcctcta ttaatggctg cttctataat 51240
ggagttgtaa atgtcgggcc aatagtagct attaccgtcg acacgtgtag tgggaactat 51300
ggccaaatgt tcaatatcta tactagtctt agccgacttg agtttatcaa taactacatc 51360
ggtatctaga tctctagaat atcccaatag gtgttccgga gaatcagtaa agaacactcc 51420
acctatagga ttcttaatat gatacgcagt gctaactggc aaacaacaag ccgcagagca 51480
taaattcaac catgaatttt ttgcgctatt aaaggcttta aaagtatcaa atcttctacg 51540
aagatctgtg gccagcgggg gataatcaga atatacacct aacgttttaa tcgtatgtat 51600
agatcctcca gtaaatgacg cgtttcctac ataacatctt tcatcatctg acacccaaaa 51660
acaaccgagt agtagtccca cattattttt tttatctata ttaacggtta taaaatttat 51720
atccgggcag tgactttgta gctctcccag atttcttttc cctcgttcat ctagcaaaac 51780
tattatttta atcccttttt cagatgcctc ttttagttta tcaaaaataa gcgcgcccct 51840
agtcgtactc agaggattac aacaaaaaga tgctatgtat atatatttct tagctagagt 51900
gataatttcg ttaaaacatt caaatgttgt caaatgatcg gatctaaaat ccatattttc 51960
tggtagtgtt tctaccagcc tacattttgc tcccgcaggt accgatgcaa atggccacat 52020
ttagttaaca taaaaactta tacatcctgt tctatcaacg attctagaat atcatcggct 52080
atatcgctaa aattttcatc aaagtcgaca tcacaaccta actcagtcaa tatattaaga 52140
agttccatga tgtcatcttc gtctatttct atatccgtat ccattgtaga ttgttgaccg 52200
attatcgagt ttaaatcatt actaatactc aatccttcag aatacaatct gtgtttcatt 52260
gtaaatttat aggcggtgta tttaagttgg tagattttca attatgtatt aatatagcaa 52320
cagtagtttt tgctcctcct tgattctagc atcctcttca ttattttctt ctacgtacat 52380
aagcatgtcc aatacgttag acaacacacc gacgatggcg gccgccacag acacgaatat 52440
gactaaaccg atgaccattt aaaaacccct ctctagcttt cacttaaact gtatcgatca 52500
ttcttttagc acatgtataa tataaaaaca ttattctatt tcgaatttag gcttccaaaa 52560
atttttcatc cgtaaaccga taataatata tatagacttg ttaatagtcg gaataaatag 52620
attaatgctt aaactatcat catctccacg attagagata caatatttac attctttttg 52680
ctgtttcgaa actttatcaa tacacgttaa tacaaaccca ggaaggagat attgaaactg 52740
aggctgttga aaatgaaacg gtgaatacaa taattcagat aatgtaaaat catgattccg 52800
tattctgatg atattagaac tgctaatgga tgtcgatggt atgtatctag gagtatctat 52860
tttaacaaag catcgatttg ctaatataca attatcattt tgattaattg ttattttatt 52920
catattctta aaaggtttca tatttatcaa ttcttctaca ttaaaaattt ccatttttaa 52980
tttatgtagc cccgcaatac tcctcattac gtttcatttt ttgtctataa tatccatttt 53040
gttcatctcg gtacatagat tatccaattg agaagcgcat ttagtagttt tgtacatttt 53100
aagtttattg acgaatcgtc gaaaactagt tatagttaac attttattat ttgataccct 53160
gatattaata cccctgccgt tactattatt tataactgat gtaacccacg taacattaga 53220
attaattatc gatagtaatg catcaacgct tccaaaattg tctattataa actcaccgat 53280
aattttttta ttgcatgttt tcatattcat taggattatc aaatctttaa tcttattacg 53340
attgtatgcg ttgatattac aagacgtcat tctaaaagac ggaggatttc catcaaatgc 53400
cagacaatca cgtacaaagt acatggaaat aggttttgtt ctattgcgca tcatagattt 53460
atatagaaca cccgtagaaa tactaatttg ttttactcta taaaatacta atgcatctat 53520
ttcatcgttt tgtataacgt ctttccaagt gtcaaattcc aaattttttt cattgatagt 53580
accaaattct tctatctctt taactacttg catagatagg taattacagt gatgcctaca 53640
tgccgttttt tgaaactgaa tagatgcgtc tagaagcgat gctacgctag tcacaatcac 53700
cactttcata tttagaatat atatatgtaa aaatatagta gaatttcatt ttgttttttc 53760
tatgctataa atgaattctc attttgcatc tgctcatact ccgttttata ttaataccaa 53820
agaaggaaga tatctggttc taaaagccgt taaagtatgc gatgttagaa ctgtagaatg 53880
cgaaggaagt aaagcttcct gcgtactcaa agtagataaa ccctcatcgc ccgcgtgtga 53940
gagaagacct tcgtccccgt ccagatgcga gagaatgaat aaccctggaa aacaagttcc 54000
gtttatgagg acggacatgc tacaaaatat gttcgcggct aatcgcgata atgtagcttc 54060
tagacttttg tcctaaaata ctattatatc cttttcgata ttaataaatc cgtgtcgtcc 54120
aggtttttta tctctttcag tatgtgaata gataggtatt ttatctctat tcatcatcga 54180
atttaagaga tccgataaac attgtttgta ttctccagat gtcagcatct gatacaacaa 54240
tatatgtgca cataaacctc tggcacttat ttcatgtacc ttccccttat cactaaggag 54300
aatagtattt gagaaatatg tatacatgat attatcatga attagatata cagaatttgt 54360
aacactctcg aaatcacacg atgtgtcggc gttaagatct aatatatcac tcgataacac 54420
attttcatct agatacacta gacatttttt aaagctaaaa tagtctttag tagtgacagt 54480
aactatgcga ttattttcat cgatgataca tttcatcggc atattattac gcttaccatc 54540
aaagactata ccatgtgtat atctaacgta ttctagcatg gttgccatac gcgcattaaa 54600
cttttcagga tctttggata gatcttccaa tctatctatt tgagaaaaca tttttatcat 54660
gttcaatagt tgaaacgtcg gatccactat atagatatta tctataaaga ttttaggaac 54720
tacgttcatg gtatcctggc gaatattaaa actatcaatg atatgattat cgttttcatc 54780
ttttatcacc atatagtttc taagatatgg gattttactt aatataatat tatttcccgt 54840
gataaatttt attagaaagg ccaaatctat aagaaaagtc ctagaattag tctgaagaat 54900
atctatatcg ccgtatagta tatttggatt aattagatat agagaatatg atccgtaaca 54960
tatacaactt ttattatggc gtctaagata ttcttccatc aacttattaa catttttgac 55020
tagggaagat acattatgac gtcccattac ttttgccttg tctattactg cgacgttcat 55080
agaatttagc atatctcttg ccaattcttc cattgatgtt acattataag aaattttaga 55140
tgaaattaca tttggagctt taatagtaag aactcctaat atgtccgtgt atgtggtcac 55200
taatacagat tgtagttcta taatcgtaaa taatttacct atattatatg tttgagtctg 55260
tttagaaaag tagctaagta tacgatcttt tatttctgat gcagatgtat caacatcgga 55320
aaaaaatctt tttttattct tttttactaa agatacaaat atgtctttgt taaaaacagt 55380
tattttctga atatttctag cttgtaattt taacatatga tattcgttca cactaggtac 55440
tctgcctaaa taggtttcta taatctttaa tgtaatatta ggaagagtat tctgatcagg 55500
attcctattc attttgagga tttaaaactc tgattattgt ctaatatggt ctctacgcaa 55560
actttttcac agagcgatag agtttttgat aactcgtttt tcttaagaaa tataaaacta 55620
ctgtttccag agctcgctct atcttttatt ttatctaatt cgatacaaac tcctgatact 55680
ggttcagaaa gtaattcatt aattttcagt cctttataga agatatttaa tatagataat 55740
acaaaatctt cagtttttga tatcgatctg attgatccta gaactagata tattaataac 55800
gtgctcatta ggcagtttat ggcagcttga taattagata tagtatattc cagttcatat 55860
ttattagata ccgcattgcc cagattttga tattctatga attcctctga aaataaatcc 55920
aaaataacta gacattctat tttttgtgga ttagtgtact ctcttccctc tatcatgttc 55980
actactggtg tccacgatga taaatatcta gagggaatat aatatagtcc ataggatgcc 56040
aatctagcaa tgtcgaataa ctgtaatttt attcttcgct cttcattatg aattgattct 56100
tgaggtataa acctaacaca aattatatta ttagactttt cgtatgtaat gtctttcatg 56160
ttataagttt ttaatcctgg aatagaatct attttaatga ggcttttaaa cgcagagttc 56220
tccaacgagt caaagcataa tactctgttg tttttcttat atacgatgtt acgattttct 56280
tctttgaatg gaataggttt ttgaattagt ttataattac aacataatag ataaggaagt 56340
gtgcaaatag tacgcggaaa aaacataata gctcccctgt tttcatccat ggttttaagt 56400
aaatgatcac tggcttcttt agtcaatgga tattcgaaca ttaaccgttt catcatcatt 56460
ggacagaatc catatttctt aatgtaaaga gtgatcaaat cattgtgttt attgtaccat 56520
cttgttgtaa atgtgtattc ggttatcgga tctgctcctt tttctattaa agtatcgata 56580
tcgatctcgt ctaagaattc aactatatcg acatatttca tttgtataca cataaccatt 56640
actaacgtag aatgtatagg aagagatgta acgggaacag ggtttgttga ttcgcaaact 56700
attctaatac ataattcttc tgttaatacg tcttgcacgt aatctattat agatgccaag 56760
atatctatat aattattttg taagatgatg ttaactatgt gatctatata agtagtgtaa 56820
taattcatgt attttgatat atgttccaac tctgtctttg tgatgtctag tttcgtaata 56880
tctatagcat cctcaaaaaa tatattcgca tatattccca agtcttcagt tctatcttct 56940
aaaaaatctt caacgtatgg aatataataa tctattttac ctcttctgat atcattaatg 57000
atatagtttt tgacactatc ttctgtcaat tgattcttat tcactatatc taagaaacgg 57060
atagcgtccc taggacgaac tactgccatt aatatctcta ttatagcttc tggacataat 57120
tcatctatta taccagaatt aatgggaact attccgtatc tatctaacat agttttaaga 57180
aagtcagaat ctaagacttg atgttcatat attggttcat acatgaaatg atctctattg 57240
atgatagtga ctatttcatt ctctgaaaat tggtaactca ttctatatat gctttccttg 57300
ttgatgaagg atagaatata ctcaatagaa tttgtaccaa caaactgttc tcttatgaat 57360
cgtatatcat catctgaaat aatcatgtaa ggcatacatt taacaattag agacttgtct 57420
cctgttatca atatactatt cttgtgataa tttatgtgtg aggcaaattt gtccacgttc 57480
tttaattttg ttatagtaga tatcaaatcc aatggagcta cagttcttgg cttaaacaga 57540
tatagttttt ctggaacaaa ttctacaaca ttattataaa ggactttggg tagataagtg 57600
ggatgaaatc ctattttaat taatgcgata gccttgtcct cgtgcagata tccaaacgct 57660
tttgtgatag tatggcattc attgtctaga aacgctctac gaatatctgt gacagatatc 57720
atctttagag aatatactag tcgcgttaat agtactacaa tttgtatttt ttaatctatc 57780
tcaataaaaa aattaatatg tatgattcaa tgtataacta aactactaac tgttattgat 57840
aactagaatc agaatctaat gatgacgtaa ccaagaagtt tatctactgc caatttagct 57900
gcattatttt tagcatctcg tttagatttt ccatcggcct tatcgaatac tcttccgtcg 57960
atatctacac aggcataaaa tgtaggagag ttactaggcc caactgattc aatacgaaaa 58020
gaccaatctc tcttagttat ttggcagtac tcattaataa cggtgacagg gttagcatct 58080
ttccaatcaa taattttttt agccggaata acatcatcaa aagacttatg atcctctctc 58140
attgattttt cgcgggatac atcatctatt atggcgtcag ccataacatc agcatccggc 58200
ttatccgcct ccgttgtcat aaaccaacga ggaggaatat cgtcggagct gtacaccata 58260
gcactacgtt gaagatcgta cagagcttta ttaacttctc gcttctccat attaagttgt 58320
ctagttagtt gtgcagcagt agctccttcg attccaatgg ttttaatagc ctcacacaca 58380
atctctgcgt cagaacgctc gtcaatatag atcttagaca tttttagaga gaactaacac 58440
aaccagcaat aaaactgaac ctactttatc atttttttat tcatcatcct ctggtggttc 58500
gtcgttccta tcgaatgtgg atctgattaa cccgtcatct ataggtgatg ctggttctgg 58560
agattctgga ggagatggat tattatctgg aagaatctct gttatttcct tgttttcatg 58620
tatcgattgc gttgtaacat taagattgcg aaatgctcta aatttgggag gcttaaagtg 58680
ttgtttgcaa tctctacacg cgtgtctaac tagtggaggt tcgtcagctg ctctagtttg 58740
aatcatcatc ggtgtagtat tcctactttt acagttagga cacggtgtat tgtatttctc 58800
gtcgagaacg ttaaaataat cgttgtaact cacatccttt attttatcta tattgtattc 58860
tactcctttc ttaatgcatt ttataccgaa taagagatag cgaaggaatt ctttttcggt 58920
gccgctagta cccttaatca tatcacatag tgttttatat tccaaatttg tggcaataga 58980
cggtttattt ctatacgata gtttgtttct ggaatccttt gagtattcta taccaatatt 59040
attctttgat tcgaatttag tttcttcgat attagatttt gtattaccta tattcttgat 59100
gtagtacttt gatgattttt ccatggccca ttctattaag tcttccaagt tggcatcatc 59160
cacatattgt gatagtaatt ctcggatatc agtagcggct accgccattg atgtttgttc 59220
attggatgag taactactaa tgtatacatt ttccatttat aacacttatg tattaacttt 59280
gttcatttat attttttcat tattatgttg atattaacaa aagtgaatat atatatgtta 59340
ataattgtat tgtggttata cggctacaat tttataatga gtgaaagtca gtgtccgatg 59400
atcaatgacg atagctttac tctgaaaaga aagtatcaaa tcgatagtgc ggagtcaaca 59460
ataaaaatgg ataagaagag gataaagttt cagaatagag ccaaaatggt aaaagaaata 59520
aatcagacaa taagagcagc acaaactcat tacgagacat tgaaactagg atacataaaa 59580
tttaagagaa tgattatgac tactactcta gaagatatag caccatctat tccaaataat 59640
cagaaaactt ataaactatt ctcggacatt tcagccatcg gcaaagcatc acagaatccg 59700
agtaagatgg tatatgctct gctgctttac atgtttccca atttgtttgg agatgatcat 59760
agattcattc gttatagaat gcatccaatg agtaaaatca aacacaagat cttctctcct 59820
ttcaaactta atcttattag aatattagtg gaagaaagat tctataataa tgaatgcaga 59880
tctaataaat ggagaataat tggaacacaa gttgataaaa tgttgatagc tgaatctgat 59940
aaatatacaa tagatgcaag gtataaccta aaacccatgt atagaatcaa gggagaatct 60000
gaagaagata ccctctttat caaacagatg gtagaacaat gtgtgacatc ccaggaattg 60060
gtggaaaaag tgttgaagat actgtttaga gatttgttca agagtggaga atacaaagcg 60120
tacagatacg atgatgatgt agaaaatgga tttattggat tggatacact aaaattaaac 60180
attgttcatg atatagttga accatgtatg cctgttcgta ggccagtggc taagatactg 60240
tgtaaagaaa tggtaaataa atactttgag aatccgctac atattattgg taaaaatctt 60300
caagagtgca ttgactttgt tagtgaatag gcatttcatc tttctccaat actaattcaa 60360
attgttaaat taataatgga tagtataaat agttattagt tataagatag taaaaataat 60420
tattagaata agagtgtagt atcatagata actctcttct ataaaaatgg attttattcg 60480
tagaaagtat cttatataca cagtagaaaa taatatagat tttttaaagg atgatacatt 60540
aagtaaagta aacaatttta ccctcaatca tgtactagct ctcaagtatc tagttagcaa 60600
ttttcctcaa cacgttatta ctaaggatgt attagctaat accaattttt ttgttttcat 60660
acatatggta cgatgttgta aagtgtacga agcggtttta cgacacgcat ttgatgcacc 60720
cacgttgtac gttaaagcat tgactaagaa ttatttatcg tttagtaacg caatacaatc 60780
gtacaaggaa accgtgcata aactaacaca agatgaaaaa tttttagagg ttgccgaata 60840
catggacgaa ttaggagaac ttataggcgt aaattatgac ttagttctta atccattatt 60900
tcacggaggg gaacccatca aagatatgga aatcattttt ttaaaactgt ttaagaaaac 60960
agacttcaaa gttgttaaaa aattaagtgt tataagatta cttatttggg catacctaag 61020
caagaaagat acaggcatag agtttgcgga taatgataga caagatatat atactctatt 61080
tcaacaaact ggtagaatcg tccatagcaa tctaacagaa acgtttagag attatatctt 61140
tcccggagat aagactagct attgggtgtg gttaaacgaa agtatagcta atgatgcgga 61200
tatcgttctt aatagacccg ccattaccat gtatgataaa attcttagtt atatatactc 61260
tgagataaaa caaggacgcg ttaataaaaa catgcttaag ttagtttata tctttgagcc 61320
tgaaaaagat atcagagaac ttctgctaga aatcatatat gatattcctg gagatatcct 61380
atctattatt gatgcaaaaa acgacgattg gaaaaaatat tttattagtt tttataaagc 61440
taattttatt aacggtaata catttattag tgatagaacg tttaacgagg acttattcag 61500
agttgttgtt caaatagatc ccgaatattt cgataatgaa cgaattatgt ctttattctc 61560
tacgagtgct gcggacatta aacgatttga tgagttagat attaataaca gttatatatc 61620
taatataatt tatgaggtga acgatatcac attagataca atggatgata tgaagaagtg 61680
tcaaatcttt aacgaggata cgtcgtatta tgttaaggaa tacaatacat acctgttttt 61740
gcacgagtcg gatcccatgg tcatagagaa cggaatacta aagaaactgt catctataaa 61800
atccaagagt agacggctga acttgtttag caaaaacatt ttaaaatatt atttagacgg 61860
acaattggct cgtctaggtc ttgtgttaga tgattataaa ggagacttgt tagttaaaat 61920
gataaaccat cttaagtctg tggaggatgt atccgcattc gttcgatttt ctacagataa 61980
aaaccctagt attcttccat cgctaatcaa aactatttta gctagttata atatttccat 62040
catcgtctta tttcaaaggt ttttgagaga taatctatat catgtagaag aattcttgga 62100
taaaagcatc catctaacca agacggataa gaaatatata cttcaattga taagacacgg 62160
tagatcatag aacagaccaa atatattatt aataatttgt atatacatag atataattat 62220
cacacatttt tgataaatgg gaactgctgc aacaattcag actcccacca aattaatgaa 62280
taaagaaaat gcagaaatga ttttggaaaa aattgttgat catatagtta tgtatattag 62340
tgacgaatca agtgattcag aaaataatcc tgaatatatt gattttcgta acagatacga 62400
agactataga tctctcatta taaaaagtga tcacgagttt gtaaagctat gtaaaaatca 62460
tgcggagaaa agttctccag aaacgcaaca aatgattatc aaacacatat acgaacaata 62520
tcttattcca gtatctgaag tactattaaa acttataatg tccatgggtg acataattac 62580
atataacgga tgtaaagaca atgaatggat gctagaacaa ctctctaccc taaactttaa 62640
caatctccgc acatggaact catgtagcat aggcaatgta acgcgtctgt tttatacatt 62700
ttttagttat ctgatgaaag ataaactaaa tatataagta taatcccatt ctaatacttt 62760
aacctgatgt attagcatct tattagaata ttaacctaac taaaagacat aacataaaaa 62820
ctcattacat agttgataaa aagcggtagg atataaatat tatggctgcc accgttccgc 62880
gttttgacga cgtgtacaaa aatgcacaaa gaagaattct agatcaagaa acatttttta 62940
gtagaggtct aagtagaccg ttaatgaaaa acacatatct atttgataat tacgcgtatg 63000
gatggatacc agaaactgca atttggagta gtagatacgc aaacttagat gcaagtgact 63060
attatcccat ttcgttggga ttacttaaaa agtttgagtt tctcatgtct ctatataaag 63120
gtcctattcc agtatacgaa gaaaaagtaa atactgaatt catagccaat ggatcgttct 63180
ctggtagata cgtatcatat cttcgaaagt tttctgctct tccaacaaac gagtttatta 63240
gttttttgtt actgacctcc atccctatct ataatatctt gttctggttt aaaaatactc 63300
agtttgatat tactaaacac acattattca gatacgttta tacagataat gccaaacacc 63360
tggcgttggc taggtatatg catcaaacag gagactataa gcctttgttt agtcgtctca 63420
aagagaatta tatatttacc ggtcccgttc caataagtat caaagatata gatcacccta 63480
atcttagtag agcaagaagt ccatccgatt atgagacatt agctaatatt agtactatat 63540
tgtactttac caagtatgat ccggtattaa tgtttttatt gttttacgta cctgggtatt 63600
caattactac aaaaattact ccagccgtag aatatctaat ggataaactg aatctaacaa 63660
agagcgacgt acaactgttg taaattattt tatgcttcgt aaaatgtagg ttttgaacca 63720
aacattcttt caaagaatga gatgcataaa actttattat ccaatagatt gactatttcg 63780
gacgtcaatc gtttaaagta aacttcgtaa aatattcttt gatcactgcc gagtttaaaa 63840
cttctatcga taattgtttc atatgtttta atatttacaa gttttttggt ccatggtaca 63900
ttagccggac aaatatatgc aaaataatat cgttctccaa gttctatagt ttctggatta 63960
tttttattat attcagtaac caaatacata ttagggttat ctgcggattt ataatttgag 64020
tgatgcattc gactcaacat aaataattct agaggagacg atctactatc aaattcggat 64080
cgtaaatctg tttctaaaga acggagaata tctatacata cctgattaga attcatccgt 64140
ccttcagaca acatctcaga cagtctggtc ttgtatgtct taatcatatt cttatgaaac 64200
ttggaaacat ctcttctagt ttcactagta cctttattaa ttctctcagg tacagatttt 64260
gaattcgacg atgccgagta tttcatcgtt gtatatttct tcttcgattg cataatcaga 64320
ttcttatata ccgcctcaaa ctctatttta aaattattaa acaatactct attattaatc 64380
agtcgttcta actctttcgc tatttctata gacttatcga catcttgact gtctatctct 64440
gtaaacacgg agtcggtatc tccatacacg ctacgaaaac gaaatctgta atctataggc 64500
aacgatgttt tcacaatcgg attaatatct ctatcgtcca tataaaatgg attacttaat 64560
ggattggcaa accgtaacat accgttagat aactctgctc catttagtac cgattctaga 64620
tacaagatca ttctacgtcc tatggatgtg caactcttag ccgaagcgta tgagtataga 64680
gcactatttc taaatcccat cagaccatat actgagttgg ctactatctt gtacgtatat 64740
tgcatggaat cataaatggc cttttcagtt gaactggtag cctgttttaa catcttttta 64800
tatctggctc tctctgccaa aaatgttctt aatagtctag gaatggttcc ttctatcgat 64860
ctatcgaaaa ttgctatttc agagatgagg ttcggtagtc taggttcaca atgaaccgta 64920
atatatctag gaggtggata tttctgaagc aagagctgat tatttatttc ttcttccaat 64980
ctattggtac taacaacgac accgactaat gtttccggag atagatttcc aaagatacac 65040
acattaggat acagactgtt ataatcaaag attaatacat tattactaaa cattttttgt 65100
tttggagcaa ataccttacc gccttcataa ggaaactttt gttttgtttc tgatctaact 65160
aagatagttt tagtttccaa caatagcttt aacagtggac ccttgatgac tgtactcgct 65220
ctatattcga ataccatgga ttgaggaagc acatatgttg acgcacccgc gtctgttttt 65280
gtttctactc cataatactc ccacaaatac tgacacaaac aagcatcatg aatacagtat 65340
ctagccatat ctaaagctat gtttagatta taatccttat acatctgagc taaatcaacg 65400
tcatcctttc cgaaagataa tttatatgta tcattaggta aagtaggaca taatagtacg 65460
actttaaatc cattttccca aatatcttta cgaattactt tacatataat atcctcatca 65520
acagtcacat aattacctgt ggttaaaacc tttgcaaatg cagcggcttt gcctttcgcg 65580
tctgtagtat cgtcaccgat gaacgtcatt tctctaactc ctctatttaa tactttaccc 65640
atgcaactga acgcgttctt ggatatagaa tccaatttgt acgaatccaa tttttcaaat 65700
ttttgaatga atgaatatag atcgaaaaat atagttccat tattgttatt aacgtgaaac 65760
gtagtattgg ccatgccgcc tactccctta tgactagact gatttctctc ataaatacag 65820
agatgtacag cttccttttt gtccggagat ctaaagataa tcttctctcc tgttaataac 65880
tctagacgat tagtaatata tctcagatca aagttatgtc cgttaaaggt aacgacgtag 65940
tcgaacgtta gttccaacaa ttgtttagct attcgtaaca aaactatttc agaacataga 66000
actagttctc gttcgtaatc catttccatt agtgactgta tcctcaaaca tcctctatcg 66060
acggcttctt gtatttcctg ttccgttaac atctcttcat taatgagcgt aaacaataat 66120
cgtttaccac ttaaatcgat ataacagtaa cttgtatgcg agattgggtt aataaataca 66180
gaaggaaact tcttatcgaa gtgacactct atatctagaa ataagtacga tcttgggata 66240
tcgaatctag gtattttttt agcgaaacag ttacgtggat cgtcacaatg ataacatcca 66300
ttgttaatct ttgtcaaata ttgctcgtcc aacgagtaac atccgtctgg agatatcccg 66360
ttagaaatat aaaaccaact aatattgaga aattcatcca tggtggcatt ttgtatgctg 66420
cgtttctttg gctcttctat caaccacata tctgcgacgg agcattttct atctttaata 66480
tctagattat aacttattgt ctcgtcaatg tctatagttc tcatctttcc caacggcctc 66540
gcattaaatg gaggaggaga caatgactga tatatttcgt ccgtcactac gtaataaaag 66600
taatgaggaa atcgtataaa tacggtctcg ccatttcgac atctggattt cagatataaa 66660
aatctgtttt caccgtgact ttcaaaccaa ttaatgcacc gaacatccat ttatagaatt 66720
tagaaatata ttttcattta aatgaatccc aaacattggg gaagagccgt atggaccatt 66780
atttttatag tactttcgca agcgggttta gacggcaaca tagaagcgtg taaacgaaaa 66840
ctatatacta tagttagcac tcttccatgt cctgcatgta gacggcacgc gactattgct 66900
ataaaggaca ataatgtcat gtctagcgat gatctgaatt atatttatta ttttttcatc 66960
agattattta acaatttggc atctgatccc aaatacgcga tcgatgtgac aaaggttaac 67020
cctttataaa cttaacccat tataaaactt atgattagtc acaactgaaa taaccgcgtg 67080
attatttttt ggtataattc tacacggcat ggtttctgtg actatgaatt caacccccgt 67140
tacattagtg aaatctttaa caaacagcaa gggttcgtca aagacataaa actcattgtt 67200
tacaatcgaa atagaccccc tatcacactt aaaataaaaa atatccttat cctttaccac 67260
caaataaaat tctgattggt caatgtgaat gtattcactt aacagttcca caaatttatt 67320
tattaactcc gaggcacata catcgtcggt attttttatg gcaaacttta ctcttccagc 67380
atccgtttct aaaaaaatat taacgagttc catttatatc atccaatatt attgaaatga 67440
cgttgatgga cagatgatac aaataagaag gtacggtacc tttgtccacc atctcctcca 67500
attcatgctc tattttgtca ttaactttaa tgtatgaaaa cagtacgcca catgcttcca 67560
tgacagtgtg taacactttg gatacaaaat gtttgacatt agtataattg tccaagactg 67620
tcaatctata atagatagta gctataatat attctatgat ggtattgaag aagatgacaa 67680
ccttggcata ttgatcattt aacacagaca tggtatcaac agatagcttg aatgaaagag 67740
aatcagtaat tggaataagc gtcttctcga tagagtgtcc gtataccaac atgtctgata 67800
ttttgatgta ttccattaaa ttatttagtt ttttcttttt attctcgtta aacagcattt 67860
ctgtcaacgg accccaacat cgttgaccga ttaagttttg attgattttt ccgtgtaagg 67920
cgtatctagt cagatcgtat agcctatcca ataatccatc gtctgtgtgt agatcacatc 67980
gtacactttt taattctcta tagaagagcg acagacatct ggagcaatta cagacagcaa 68040
tttctttatt ctctacagat gtaagatact tgaagacatt cctatgatga tgcagaattt 68100
tggataacac ggtattgatg gtatctgtta ccataattcc tttgatggct gatagtgtca 68160
gagcacaaga tttccaatct ttgacaattt ttagcaccat tatctttgtt ttgatatcta 68220
tatcagacag catggtgcgt ctgacaacac agggattaag acggaaagat gaaatgattc 68280
tctcaacatc ttcaatggat accttgctat tttttctggc attatctata tgtgcgagaa 68340
tatcctctag cctgcaggtc aattcggtag ttgcgatata cataaactga tcactaattc 68400
caaacccacc cactttttat agtaagtttt tcacccataa ataataaata caataattaa 68460
tttctcgtaa aagtagaaaa tatattctaa tttattgcac ggtaaggaag tagtcgaaac 68520
gaattcgccc ttgcttgcaa gccaccatgg cctcctccga ggacgtcatc aaggagttca 68580
tgcgcttcaa ggtgcgcatg gagggctccg tgaacggcca cgagttcgag atcgagggcg 68640
agggcgaggg ccgcccctac gagggcaccc agaccgccaa gctgaaggtg accaagggcg 68700
gccccctgcc cttcgcctgg gacatcctgt ccccccagtt ccagtacggc tccaaggtgt 68760
acgtgaagca ccccgccgac atccccgact acaagaagct gtccttcccc gagggcttca 68820
agtgggagcg cgtgatgaac ttcgaggacg gcggcgtggt gaccgtgacc caggactcct 68880
ccctgcagga cggctccttc atctacaagg tgaagttcat cggcgtgaac ttcccctccg 68940
acggccccgt aatgcagaag aagactatgg gctgggaggc ctccaccgag cgcctgtacc 69000
cccgcgacgg cgtgctgaag ggcgagatcc acaaggccct gaagctgaag gacggcggcc 69060
actacctggt ggagttcaag tccatctaca tggccaagaa gcccgtgcag ctgcccggct 69120
actactacgt ggactccaag ctggacatca cctcccacaa cgaggactac accatcgtgg 69180
agcagtacga gcgcgccgag ggccgccacc acctgttcct gtaggcgcgc ctataagggc 69240
gaattcgcgg cctcgacgct agagaatcag tatccttttt gatgatagtg gatctcaatg 69300
acatgggacg tctaaacctt cttattctat caccagattg catggtgatt tgtcttcttt 69360
cttttatcat aatgtaatct ctaaattcat cggcaaattg tctatatcta aaatcataat 69420
atgagatgtt tacctctaca aatatctgtt cgtccaatgt tagagtattt acatcagttt 69480
tgtattccaa attaaacatg gcaacggatt taattttata ttcctctatt aagtcctcgt 69540
cgataataac agaatgtaga taatcattta atccatcgta catggttgga agatgcttgt 69600
tgacaaaatc tttaattgtc ttgatgaagg tgggactata tctaacatct tgattaataa 69660
aatttataac attgtccata ggatactttg taactagttt tatacacatc tcttcatcgg 69720
taagtttaga cagaatatcg tgaacaggtg gtatattata ttcatcagat atacgaagaa 69780
caatgtccaa atctatattg tttaatatat tatatagatg tagcgtagct cctacaggaa 69840
tatctttaac taagtcaatg atttcatcaa ccgttagatc tattttaaag ttaatcatat 69900
aggcattgat ttttaaaagg tatgtagcct tgactacatt ctcattaatt aaccattcca 69960
agtcactgtg tgtaagaaga ttatattcta tcataagctt gactacattt ggtcccgata 70020
ccattaaaga attcttatga tataaggaaa cagcttttag gtactcatct actctacaag 70080
aattttggag agccttaacg atatcagtga cgtttattat ttcaggagga aaaaacctaa 70140
cattgagaat gtcggagtta atagcttcca gatacagtga ttttggcaat agtccgtgta 70200
atccataatc cagtaacacg agctggtgct tgctagacac cttttcaatg tttaattttt 70260
ttgaaataag ctttgataaa gccttcctcg caaattccgg atacatgaac atgtcggcga 70320
catgattaag tattgttttt tcattatttt tatattttct caacaagttc tcaatacccc 70380
aatagatgat agaatatcac ccaatgcgtc catgttgtct atttccaaca ggtcgctata 70440
tccaccaata gaagtttttc caaaaaagat tctaggaaca gttctaccac cagtaatttg 70500
ttcaaaataa tcacgcaatt cattttcggg tttaaattct ttaatatcga caatttcata 70560
cgctcctctt ttgaaactaa acttatttag aatatccagt gcatttctac aaaaaggaca 70620
tgtatacttg acaaaaattg tcactttgtt attggccaac ctttgttgta caaattcctc 70680
ggccatttta atatttaagt gatataaaac tatctcgact tatttaactc tttagtcgag 70740
atatatggac gcagatagct atatgatagc caactacaga aggcaaacgc tataaaaaac 70800
ataattacaa cgagcatatt tataaatatt tttattcagc attacttgat atagtaatat 70860
taggcacagt caaacattca accactctcg atacattaac tctctcattt tctttaacaa 70920
attctgcaat atcttcgtaa aaagattctt gaaacttttt agaatatcta tcgactctag 70980
atgaaatagc gttcgtcaac atactatgtt ttgtatacat aaaggcgcct attttaacag 71040
tttctagtga caaaatgcta gcgatcctag gatcctttag aatcacatag attgacgatt 71100
cgtctctctt agtaactcta gtaaaataat catacaatct agtacgcgaa ataatattat 71160
ccttgacttg aggagatcta aacaatctag ttttgagaac atcgataagt tcatcgggaa 71220
tgacatacat actatcttta atagaactct tttcatccag ttgaatggat tcgtccttaa 71280
ccaactgatt aatgagatct tctattttat cattttccag atgatatgta tgtccattaa 71340
agttaaattg tgtagcgctt ctttttagtc tagcagccaa tactttaaca tcactaatat 71400
cgatatacaa aggagatgat ttatctatgg tattaagaat tcgtttttcg acatctgtca 71460
aaaccaattc ctttttgcct gtatcatcca gttttccatc ctttgtaaag aaattatttt 71520
ctactagact attaataaga ctgataagga ttcctccata attgcacaat ccaaactttt 71580
taacaaaact agactttaca agatctacag gaatgcgtac ttcaggtttt ttagcttgtg 71640
attttttctt ttgcggacat tttctagtaa ccaactcatc taccatttca ttgattttag 71700
cagtgaaata agctttcaat gcacgggcac tgatactatt gaaaacgagt tgatcttcaa 71760
attccgccat ttaagttcac caaacaactt ttaaatacaa atatatcaat agtagtagaa 71820
taagaactat aaaaaaaata ataattaacc aataccaacc ccaacaaccg gtattattag 71880
ttgatgtggt agttttctca tcacttagaa cagatttaac aatttctata aagtctgtca 71940
aatcatcttc cggagacccc ataaatacac caaatatagc ggcgtacaac ttatccattt 72000
atacattgaa tattggcttt tctttatcgc tatcttcatc atattcatca tcaatatcaa 72060
caagtcccag attacgagcc agatcttctt ctacattttc agtcattgat acacgttcac 72120
tatctccaga gagtccgata acgttagcca ccacttctct atcaatgatt agtttcttga 72180
gcgcgaatgt aatttttgtt tccgttccgg atctatagaa gacgataggt gtgataattg 72240
ccttggccaa ttgtctttct cttttactga gtgattctag ttcaccttct atagatctga 72300
gaatggatga ttctccagtc gaaacatatt ctaccatgga tccgtttaat ttgttgatga 72360
agatggattc atccttaaat gttttctctg taatagtttc caccgaaaga ctatgcaaag 72420
aatttggaat gcgttccttg tgcttaatgt ttccatagac ggcttctaga agttgataca 72480
acataggact agccgcggta acttttattt ttagaaagta tccatcgctt ctatcttgtt 72540
tagatttatt tttataaagt ttagtctctc cttccaacat aataaaagtg gaagtcattt 72600
gactagataa actatcagta agttttatag agatagacga acaattagcg tattgagaag 72660
catttagtgt aacgtattcg atacattttg cattagattt actaatcgat tttgcatact 72720
ctataacacc cgcacaagtc tgtagagaat cgctagatgc agtaggtctt ggtgaagttt 72780
caactctctt cttgattacc ttactcatga ttaaacctaa ataattgtac tttgtaatat 72840
aatgatatat attttcactt tatctcattt gagaataaaa atgtttttgt ttaaccactg 72900
catgatgtac agatttcgga atcgcaaacc accagtggtt ttattttatc cttgtccaat 72960
gtgaattgaa tgggagcgga tgcgggtttc gtacgtagat agtacattcc cgtttttaga 73020
ccgagactcc atccgtaaaa atgcatactc gttagtttgg aataactcgg atctgctata 73080
tggatattca tagattgact ttgatcgatg aaggctcccc tgtctgcagc catttttatg 73140
atcgtctttt gtggaatttc ccaaatagtt ttataaactc gcttaatatc ttctggaagg 73200
tttgtattct gaatggatcc accatctgcc ataatcctat tcttgatctc atcattccat 73260
aattttctct cggttaaaac tctaaggaga tgcggattaa ctacttgaaa ttctccagac 73320
aatactctcc gagtgtaaat attactggta tacggttcca ccgactcatt atttcccaaa 73380
atttgagcag ttgatgcagt cggcataggt gccaccaata aactatttct aagaccgtat 73440
gttctgattt tatcttttag aggttcccaa ttccaaagat ccgacggtac aacattccaa 73500
agatcatatt gtagaatacc gttactggcg tacgatccta catatgtatc gtatggtcct 73560
tccttctcag ctagttcaca actcgcctct aatgcaccgt aataaatggt ttcgaagatc 73620
ttcttattta gatcttgtgc ttccaggcta tcaaatggat aatttaagag aataaacgcg 73680
tccgctaatc cttgaacacc aataccgata ggtctatgtc tcttattaga gatttcagct 73740
tctggaatag gataataatt aatatctata attttattga gatttctgac aattactttg 73800
accacatcct tcagtttgag aaaatcaaat cgcccatcta ttacaaacat gttcaaggca 73860
acagatgcca gattacaaac ggctacctca ttagcatccg catattgtat tatctcagtg 73920
caaagattac tacacttgat agttcctaaa ttttgttgat tactcttttt gttacacgca 73980
tccttataaa gaatgaatgg agtaccagtt tcaatctgag attctataat cgctttccag 74040
acgactcgag cctttattat agatttgtat ctcctttctc tttcgtatag tgtatacaat 74100
cgttcgaact cgtctcccca aacattgtcc aatccaggac attcatccgg acacatcaac 74160
gaccactctc cgtcatcctt cactcgtttc ataaagagat caggaatcca aagagctata 74220
aatagatctc tggttctatg ttcctcgttt cctgtattct ttttaagatc gaggaacgcc 74280
ataatatcag aatgccacgg ttccaagtat atggccataa ctccaggccg tttgtttcct 74340
ccctgatcta tgtatctagc ggtgttatta taaactctca acattggaat aataccgttt 74400
gatataccat tggtaccgga gatatagctt ccactggcac gaatattact aattgataga 74460
cctattcccc ctgccatttt agagattaat gcgcatcgtt ttaacgtgtc atagataccc 74520
tctatgctat catcgatcat gttaagtaga aaacagctag acatttggtg acgactagtt 74580
cccgcattaa ataaggtagg agaagcgtgc gtaaaccatt tttcagaaag tagattgtac 74640
gtctcaatag ctgagtctat atcccattga tgaattccta ctgcgacacg cattaacatg 74700
tgctgaggtc tttcaacgat cttgttgttt attttcaaca agtaggattt ttccaaagtt 74760
ttaaaaccaa aatagttgta tgaaaagtct cgttcgtaaa taataaccga gttgagttta 74820
tccttatatt tgttaactat atccatggtg atacttgaaa taatcggaga atgtttccca 74880
tttttaggat taacatagtt gaataaatcc tccatcactt cactaaatag tttttttgtt 74940
tccttgtgta gatttgatac ggctattctg gcggctaaaa tggcataatc cggatgttgt 75000
gtagtacaag tggctgctat ttcggctgcc agagtgtcca attctaccgt tgttactcca 75060
ttatatattc cttgaataac cttcatagct attttaatag gatctatatg atccgtgttt 75120
aagccataac ataattttct aatacgagac gtgattttat caaacatgac attttccttg 75180
tatccatttc gtttaatgac aaacattttt gttggtgtaa taaaaaaatt atttaacttt 75240
tcattaatag ggatttgacg tacgtagcgt acaaaatgat cgttcctggt atatagataa 75300
agagtcctat atatttgaaa atcgttacgg ctcgattaaa ctttaatgat tgcatagtga 75360
atatatcatt aggatttaac tccttgacta tcatggcggc gccagaaatt accatcaaaa 75420
gcattaatac agttatgccg atcgcagtta gaacggttat agcatccacc atttatatct 75480
aaaaattaga tcaaagaata tgtgacaaag tcctagttgt atactgagaa ttgacgaaac 75540
aatgtttctt acatattttt ttcttattag taactgactt aatagtagga actggaaagc 75600
tagacttgat tattctataa gtatagatac ccttccaaat aatattctct ttgataaaag 75660
ttccagaaaa tgtagaattt tttaaaaagt tatcttttgc tattaccaag attgtgttta 75720
gacgcttatt attaatatga gtgatgaaat ccacaccgcc tctagatatc gcctttattt 75780
ccacattaga tggtaaatcc aatagtgaaa ctatcttttt aggaatgtat ggactcgcgt 75840
ttagaggagt gaacgtcttg ggcgtcggaa aggatgattc gtcaaacgaa taaacaattt 75900
cacaaatgga tgttaatgta ttagtaggaa atttcttgac gctattggaa ttgaagattc 75960
taatggatga tgttctacct atttcatccg ataacatgtt aatttccgac accaacggtt 76020
ttaatatttc gatgatatac ggtagtctct ctttcggact tatatagctt attccacaat 76080
acgagtcatt atatactcca aaaaacaaaa taactagtat aaaatctgta tcgaatggga 76140
aaaacgaaat tatcgacata ggtatagaat ccggaacatt gaacgtatta atacttaatt 76200
ctttttctgt ggtaagtacc gataggttat tgacattgta tggttttaaa tattctataa 76260
cttgagactt gatagatatt agtgatgaat tgaaaattat ttttatcacc acgtgtgttt 76320
caggatcatc gtcgacgcct gtcaaccaac cgaatggagt aaaataaata tcattaatat 76380
atgctctaga tattagtatt tttatcaatc ctttgattat catcttctcg taggcgaatg 76440
attccatgat caagagtgat ttgagaacat cctccggagt attaatgggc ttagtaaaca 76500
gtccatcgtt gcaataataa aagttatcca agttaaagga tattatgcat tcgtttaaag 76560
atatcacctc atctgacgga gacaattttt tggtaggttt tagagacttt gaagctactt 76620
gtttaacaaa gttattcatc gtcgtctact attctattta attttgtagt taatttatca 76680
catatcacat taattgactt tttggtccat ttttccatac gtttatattc ttttaatcct 76740
gcgttatccg tttccgttat attcagggat agatcttgca agttaaatag aatgctctta 76800
aataatgtca ttttcttatc cgctaaaaat ttaaagaatg tataaacctt tttcagagat 76860
ttgaaactct taggtggtgt cctagtacac aatatcataa acaaactaat aaacattcca 76920
cattcagatt ccaacagctg attaacttcc acattaatac agcctatttt cgctccaaat 76980
gtacattcga aaaatctgaa taaaacatcg atgtcacaat ttgtattatc caatacagaa 77040
tgtttgtgat tcgtgttaaa accatcggag aaggaataga aataaaaatt attatagtgg 77100
tggaattcag ttggaatatt gcctccggag tcataaaagg atactaaaca ttgtttttta 77160
tcataaatta cacatttcca atgagacaaa taacaaaatc caaacattac aaatctagag 77220
gtagaacttt taattttgtc tttaagtata tacgataaga tatgtttatt cataaacgcg 77280
tcaaattttt catgaatcgc taaggagttt aagaatctca tgtcaaattg tcctatataa 77340
tccacttcgg atccataagc aaactgagag actaagttct taatacttcg attgctcatc 77400
caggctcctc tctcaggctc tattttcatc ttgacgacct ttggattttc accagtatgt 77460
attcctttac gtgataaatc atcgattttc aaatccattt gtgagaagtc tatcgcctta 77520
gatacttttt cccgtagtcg aggtttaaaa aaatacgcta acggtatact agtaggtaac 77580
tcaaagacat catatataga atggtaacgc gtctttaact cgtcggttaa ctctttcttt 77640
tgatcgagtt cgtcgctact attgggtctg ctcaggtgcc ccgactctac tagttccaac 77700
atcataccga taggaataca agacactttg ccggcggttg tagatttatc atatttttcc 77760
actacatatc cgttacaatt tgttaaaaat ttagatacat ctatattgct acataatcca 77820
gctagtgaat atatatgaca taataaattg gtaaatccta gttctggtat tttactaatt 77880
actaaatctg tatatctttc catttatcat ggaaaagaat ttaccagata tcttcttttt 77940
tccaaactgc gttaatgtat tctcttacaa atattcacaa gatgaattca gtaatatgag 78000
taaaacggaa cgtgatagtt tctcattggc cgtgtttcca gttataaaac atagatggca 78060
taacgcacac gttgtaaaac ataaaggaat atacaaagtt agtacagaag cacgtggaaa 78120
aaaagtatct cctccatcac taggaaaacc cgcacacata aacctaaccg cgaagcaata 78180
tatatacagt gaacacacaa taagctttga atgttatagt tttctaaaat gtataacaaa 78240
tacagaaatc aattcgttcg atgagtatat attaagagga ctattagaag ctggtaatag 78300
tttacagata ttttccaatt ccgtaggtaa acgaacagat actataggtg tactagggaa 78360
taagtatcca tttagcaaaa ttccattggc ctcattaact cctaaagcac aacgagagat 78420
attttcagcg tggatttctc atagacctgt agttttaact ggaggaactg gagtgggtaa 78480
gacgtcacag gtacccaagt tattgctttg gtttaattat ttatttggtg gattctctac 78540
tctagataaa atcactgact ttcacgaaag accagtcatt ctatctcttc ctaggatagc 78600
tttagttaga ttgcatagca ataccatttt aaaatcattg ggatttaagg tactagatgg 78660
atctcctatt tctttacggt acggatctat accggaagaa ttaataaaca aacaaccaaa 78720
aaaatatgga attgtatttt ctacccataa gttatctcta acaaaactat ttagttatgg 78780
cactcttatt atagacgaag ttcatgagca tgatcaaata ggagatatta ttatagcagt 78840
agcgagaaag catcatacga aaatagattc tatgttttta atgactgcca cattagagga 78900
tgaccgagaa cggctaaaag tatttttacc taatcccgca tttatacata ttcctggaaa 78960
tacactgttt aaaattagcg aggtatttat tcataataag ataaatccat cttccagaat 79020
ggcatacata gaagaagaaa agagaaattt agttactgct atacagatgt atactcctcc 79080
tgatggatca tccggtatag tctttgtggc atccgttgca cagtgtcacg aatataaatc 79140
atatttagaa aaaagattac cgtatgatat gtatattatt catggtaagg tcttagatat 79200
agacgaaata ttagaaaaag tgtattcatc acctaatgta tcgataatta tttctactcc 79260
ttatttggaa tccagcgtta ctatacgcaa tgttacacac atttatgata tgggtagagt 79320
ttttgtcccc gctccttttg gaggatcgca acaatttatt tctaaatcta tgagagatca 79380
acgaaaagga agagtaggaa gagttaatcc tggtacatac gtctatttct atgatctgtc 79440
ttatatgaag tctatacagc gaatagattc agaatttcta cataattata tattgtacgc 79500
taataagttt aatctaacac tccccgaaga tttgtttata atccctacaa atttggatat 79560
tctatggcgt acaaaggaat atatagactc gttcgatatt agtacagaaa catggaataa 79620
attattatcc aattattata tgaagatgat agagtatgct aaactttatg tactaagtcc 79680
tattctcgct gaggagttgg ataactttga gaggacggga gaattaacta gtattgtacg 79740
agaagccatt ttatctctaa atttacgaat taagatttta aattttaaac ataaagatga 79800
tgatacgtat atacactttt gtaaaatatt attcggtgtc tataacggaa caaacgctac 79860
tatatattat catagacctc taacgggata tatgaatatg atttcagata ctatatttgt 79920
tcctgtagat aataactaaa aatcaaactc taatgaccac atcttttttt agagatgaaa 79980
aattttccac atctcctttt gtagacacga ctaaacattt tgcagaaaaa agtttattag 80040
tgtttagata atcgtatact tcatcagtgt agatagtaaa tgtgaacaga taaaaggtat 80100
tcttgctcaa tagattggta aattccatag aatatattaa tcctttcttc ttgagatccc 80160
acatcatttc aaccagagac gttttatcca atgatttacc tcgtactata ccacatacaa 80220
aactagattt tgcagtgacg tcgtacctgg tattcctacc aaacaaaatt ttacttttag 80280
ttcttttaga aaattctaag gtagaatctc tatttgccaa tatgtcatct atggaattac 80340
cactagcaaa aaatgataga aatatatatt gatacatcgc agctggtttt gatctactat 80400
actttaaaaa cgaatcagat tccataattg cctgtatatc atcagctgaa aaactatgtt 80460
ttacacgtat tccttcggca tttcttttta atgatatatc ttgtttagac aatgataaag 80520
ttatcatgtc catgagagac gcgtctccgt atcgtataaa tatttcatta gatgttagac 80580
gcttcattag gggtatactt ctataaggtt tcttaatcag tccatcattg gttgcgtcaa 80640
gaactactat cggatgttgt tgggtatctc tagtgttaca catggcctta ctaaagtttg 80700
ggtaaataac tatgatatct ctattaatta tagatgcata tatttcattt gtcaaggata 80760
ttagtatcga cttgctatcg tcattaatac gtgtaatgta atcatataaa tcatgcgata 80820
gccaaggaaa atttaaatag atgttcatca tataatcgtc gctataattc atattaatac 80880
gttgacattg actaatttgt aatatagcct cgccacgaag aaagctctcg tattcagttt 80940
catcgataaa ggataccgtt aaatataact ggttgccgat agtctcatag tctattaagt 81000
ggtaagtttc gtacaaatac agaatcccta aaatattatc taatgttgga ttaatcttta 81060
ccataactgt ataaaatgga gacggagtca taactatttt accgtttgta cttactggaa 81120
tagatgaagg aataatctcc ggacatgctg gtaaagaccc aaatgtctgt ttgaagaaat 81180
ccaatgttcc aggtcctaat ctcttaacaa aaattacgat attcgatccc gatatccttt 81240
gcattctatt taccagcata tcacgaacta tattaagatt atctatcatg tctattctcc 81300
caccgttata taaatcgcct ccgctaagaa acgttagtat atccatacaa tggaatactt 81360
catttctaaa atagtattcg ttttctaatt ctttaatgtg aaatcgtata ctagaaaggg 81420
aaaaattatc tttgagtttt ccgttagaaa agaaccacga aactaatgtt ctgattgcgt 81480
ccgattccgt tgctgaatta atggatttac accaaaaact catataactt ctagatgtag 81540
aagcattcgc taaaaaatta gtagaatcaa aggatataag tagatgttcc aacaagtgag 81600
caattcccaa gatttcatct atatcattct cgaatccgaa attagaaatt cccaagtaga 81660
tatccttttt catccgatcg ttgatgaaaa tacgaacttt attcggtaag acaatcattt 81720
actaaggagt aaaataggaa gtaatgttcg tatgtcgtta tcatcgtata aattaaaggt 81780
gtgtttttta ccattaagtg acattataat tttaccaata ttggaattat aatataggtg 81840
tatttgcgca ctcgcgacgg ttgatgcatc ggtaaatata gctgtatcta atgttctagt 81900
cggtatttca tcatttcgct gtctaataat agcgttttct ctatctgttt ccattacagc 81960
tgcctgaagt ttattggtcg gataatatgt aaaataataa gaaatacata cgaataacaa 82020
aaataaaata agatataata aagatgccat ttagagatct aattttgttc aacttgtcca 82080
aattcctact tacagaagat gaggaatcgt tggagatagt gtcttcctta tgtagaggat 82140
ttgaaatatc ttataatgac ttgataactt actttccaga taggaaatac cataaatata 82200
tttataaagt atttgaacat gtagatttat cggaggaatt aagtatggaa ttccatgata 82260
caactctgag agatttagtc tatcttagat tgtacaagta ttccaagtgt atacggccgt 82320
gttataaatt aggagataat ctaaaaggca tagttgttat aaaggacagg aatatttata 82380
ttagggaagc aaatgatgac ttgatagaat atctcctcaa ggaatacact cctcagattt 82440
atacatattc taatgagcgc gtccccataa ctggttcaaa attaattctt tgtggatttt 82500
ctcaagttac atttatggcg tatacaacgt cgcatataac aacaaataaa aaggtagatg 82560
ttctcgtttc caaaaaatgt atagatgaac tagtcgatcc aataaattat caaatacttc 82620
aaaatttatt tgataaagga agcggaacaa taaacaaaat actcaggaag atattttatt 82680
cggtaacagg tggccaaact ccataggtag ctttttctat ttcggatttt agaatttcca 82740
aattcaccag cgatttatcg gttttggtga aatccaagga tttattaatg tccacaaatg 82800
ccatttgttt tgtctgtgga ttgtatttga aaatggaaac gatgtagtta gatagatgcg 82860
ctgcgaagtt tcctattagg gttccgcgct tcacgtcacc cagcatactt gaatcaccat 82920
cctttaaaaa aatgataaga tatcaacatg gagtatatca tactcggatt ttaattcttc 82980
tactgactca ctgacatttt cacaaatact acaatacggt ttaccgaaaa taatcagtac 83040
gttcttcatt tatgggtatc aaaaacttaa aatcgttact gctggaaaat aaatcactga 83100
cgatattaga tgataattta tacaaagtat acaatggaat atttgtggat acaatgagta 83160
tttatatagc cgtcgccaat tgtgtcagaa acttagaaga gttaactacg gtattcataa 83220
aatacgtaaa cggatgggta aaaaagggag ggcatgtaac cctttttatc gatagaggaa 83280
gtataaaaat taaacaagac gttagagaca agagacgtaa atattctaaa ttaaccaagg 83340
acagaaaaat gctagaatta gaaaagtgta catccgaaat acaaaatgtt accggattta 83400
tggaagaaga aataaaggca gaaatgcaat taaaaatcga taaactcaca tttcaaatat 83460
atttatctga ttctgataac ataaaaatat cattgaatga gatactaaca catttcaaca 83520
ataatgagaa tgttacatta ttttattgtg atgaacgaga cgcagaattc gttatgtgtc 83580
tcgaggctaa aacacatttc tctaccacag gagaatggcc gttgataata agtaccgatc 83640
aggatactat gctatttgca tctgctgata atcatcctaa gatgataaaa aacttaactc 83700
aactgtttaa atttgttccc tcggcagagg ataactattt agcaaaatta acggcgttag 83760
tgaatggatg tgatttcttt cctggactct atggggcatc tataacaccc accaacttaa 83820
acaaaataca attgtttagt gattttacaa tcgataatat agtcactagt ttggcaatta 83880
aaaattatta tagaaagact aactctaccg tagacgtgcg taatattgtt acgtttataa 83940
acgattacgc taatttagac gatgtctact cgtatattcc tccttgtcaa tgcactgttc 84000
aagaatttat attttccgca ttagatgaaa aatggaatga atttaaatca tcttatttag 84060
agaccgttcc gttaccctgt caattaatgt acgcgttaga accacgtaag gagattgatg 84120
tttcagaagt taaaacttta tcatcttata tagatttcga aaatactaaa tcagatatcg 84180
atgttataaa atctatatcc tcgatcttcg gatattctaa cgaaaactgt aacacgatag 84240
tattcggcat ctataaggat aatttactac tgagtataaa tagttcattt tactttaacg 84300
atagtctgtt aataaccaat actaaaagtg ataatataat aaatataggt tactagatta 84360
aaaatggtgt tccaactcgt gtgctctacg tgcggcaaag atatttctca cgaacgatat 84420
aaattgatta tacgaaaaaa atcattaaag gatgtactcg tcagtgtaaa gaacgaatgt 84480
tgtaggttaa aattatctac acaaatagaa cctcaacgta acttaacagt gcaacctcta 84540
ttggatataa actaatatgg atccggttaa ttttatcaag acatatgcgc ctagaggttc 84600
tattattttt attaattata ccatgtcatt aacaagtcat ttgaatccat cgatagaaaa 84660
acatgtgggt atttattatg gtacgttatt atcggaacac ttggtagttg aatctaccta 84720
tagaaaagga gttcgaatag tcccattgga tagttttttt gaaggatatc ttagtgcaaa 84780
agtatacatg ttagagaata ttcaagttat gaaaatagca gctgatacgt cattaacttt 84840
attgggtatt ccgtatggat ttggtcatga tagaatgtat tgttttaaat tggtagctga 84900
ctgttataaa aatgccggta ttgatacatc gtctaaacga atattaggta aagatatttt 84960
tctgagccaa aacttcacag acgataatag atggataaag atatatgatt ctaataattt 85020
aacattttgg caaattgatt accttaaagg gtgagttaat atgcataact actcctccgt 85080
tgttttttcc ctcgttcttt ttcttaacgt tgtttgccat cactctcata atgtaaagat 85140
attctaaaat ggtaaacttt tgcatatcgg acgcagaaat tggtataaat gttgtaattg 85200
tattatttcc cgtcaatgga ctagtcacag ctccatcagt tttatatcct ttagagtatt 85260
tctcactcgt gtctagcatt ctagagcatt ccatgatctg tttatcgttg atattggccg 85320
gaaagataga ttttttattt tttattatat tactattggc aattgtagat ataacttctg 85380
gtaaatattt ttctaccttt tcaatctctt ctattttcaa gccggctata tattctgcta 85440
tattgttgct agtatcaata ccttttctgg ctaagaagtc atatgtggta ttcactatat 85500
cagttttaac tggtagttcc attagccttt ccacttctgc agaataatca gaaattggtt 85560
ctttaccaga aaatccagct actataatag gctcaccgat gatcattggc aaaatcctat 85620
attgtaccag attaatgaga gcatatttca tttccaataa ttctgctagt tcttgagaca 85680
ttgatttatt tgatgaatct agttggttct ctagatactc taccatttct gccgcataca 85740
ataacttgtt agataaaatc agggttatca aagtgtttag cgtggctaga atagtgggct 85800
tgcatgtatt aaagaatgcg gtagtatgag taaaccgttt taacgaatta tatagtctcc 85860
agaaatctgt ggcgttgcat acatgagccg aatgacatcg aagattgtcc aatattttta 85920
atagctgctc tttgtccatt atttctatat ttgactcgca acaattgtag ataccattaa 85980
tcaccgattc ctttttcgat gctggacaat agcacaattg tttagctttg gactctatgt 86040
attcagaatt aatagatata tctctcaata cagattgcac tatacatttt gaaactatgt 86100
caaaaattgt agaacgacgc tgttctgcag ccatttaact ttaaataatt tacaaaaatt 86160
taaaatgagc atccgtataa aaatcgataa actgcgccaa attgtggcat atttttcaga 86220
gttcagtgaa gaagtgtcta taaatgtaga ctcgacggat gagttaatgt atatttttgc 86280
cgccttgggc ggatctgtaa acatttgggc cattatacct ctcagtgcat cagtgtttta 86340
ccgaggagcc gaaaacattg tgtttaatct tcctgtgtcc aaggtaaaat cgtgtttgtg 86400
tagttttcac aatgatgcca tcatagatat agaacctgat ctggaaaata atctagtaaa 86460
actttctagt tatcatgtag taagtgtcga ttgtaataag gaactgatgc ctattaggac 86520
agatactact atttgtctaa gtatagatca aaagaaatct tatgtgttta attttcacaa 86580
gtatgaagaa aaatgttgtg gtagaaccgt cattcattta gaatggttgt tgggctttat 86640
caagtgtatt agtcagcatc agcatctggc tattatgttt aaagatgaca atattattat 86700
gaagactcct ggtaatactg atgcattttc cagggaatat tctatgactg aatgttctca 86760
agaactacaa aagttttctt tcaaaatagc tatctcgtct ctcaacaaac tacgaggatt 86820
caaaaagaga gtcaatgttt ttgaaactag aatcgtaatg gataatgacg ataacatttt 86880
aggaatgttg ttttcggata gagttcaatc ctttaagatc aacatcttta tggcgttttt 86940
agattaatac tttcaatgag ataaatatgg gtggcagagt aagtgttgag ctccctaaac 87000
gggatccgcc tccgggagta cccactgatg agatgttatt aaacgtggat aaaatgcatg 87060
acgtgatagc tcccgctaag cttttagaat atgtgcatat aggaccacta gcaaaagata 87120
aagaggataa agtaaagaaa agatatccag agtttagatt agtcaacaca ggacccggtg 87180
gtctttcggc attgttaaga caatcgtata atggaaccgc acccaattgc tgtcgcactt 87240
ttaatcgtac tcattattgg aagaaggatg gaaagatatc agataagtat gaagagggtg 87300
cagtattaga atcgtgttgg ccagacgttc acgacactgg aaaatgcgat gttgatttat 87360
tcgactggtg tcagggggat acgttcgata gaaacatatg ccatcagtgg atcggttcag 87420
cctttaatag gagtaataga actgtagagg gtcaacaatc gttaataaat ctgtataata 87480
agatgcaaac attatgtagt aaagatgcta gtgtaccaat atgcgaatca tttttgcatt 87540
atttacgcgc acacaataca gaagatagca aagagatgat cgattatatt ctaagacaac 87600
agtctgcgga ctttaaacag aaatatatga gatgtagtta tcccactaga gataagttag 87660
aagagtcatt aaaatatgcg gaacctcgag aatgttggga tccagagtgt tcgaatgcca 87720
atgttaattt cttactaaca cgtaattata ataatttagg actttgcaat attgtacgat 87780
gtaataccag cgtgaacaac ttacagatgg ataaaacttc ctcattaaga ttgtcatgtg 87840
gattaagcaa tagtgataga ttttctactg ttcccgtcaa tagagcaaaa gtagttcaac 87900
ataatattaa acattcgttc gacctaaaat tgcatttgat cagtttatta tctctcttgg 87960
taatatggat actaattgta gctatttaaa tgggtgccgc ggcaagcata cagacgacgg 88020
tgaatacact cagcgaacgt atctcgtcta aattagaaca agaagcgaac gctagtgctc 88080
aaacaaaatg tgatatagaa atcggaaatt tttatatccg acaaaaccat ggatgtaacc 88140
tcactgttaa aaatatgtgc tctgcggacg cggatgctca gttggatgct gtgttatcag 88200
ccgctacaga aacatatagt ggattaacac cggaacaaaa agcatacgtg ccagctatgt 88260
ttactgctgc gttaaacatt cagacgagtg taaacactgt tgttagagat tttgaaaatt 88320
atgtgaaaca gacttgtaat tctagcgcgg tcgtcgataa caaattaaag atacaaaacg 88380
taatcataga tgaatgttac ggagccccag gatctccaac aaatttggaa tttattaata 88440
caggatctag caaaggaaat tgtgccatta aagcgttgat gcaattgacg actaaggcca 88500
ctactcaaat agcacctaga caagttgctg gtacaggagt tcagttttat atgattgtta 88560
tcggtgttat aatattggca gcgttgttta tgtactatgc caagcgtatg ttgttcacat 88620
ccaccaatga taaaatcaaa cttattttag ccaataagga aaacgtccat tggactactt 88680
acatggacac attctttaga acttctccga tggttattgc taccacggat atgcaaaact 88740
gaaaatatat tgataatatt ttaatagatt aacatggaag ttatcgctga tcgtctagac 88800
gatatagtga aacaaaatat agcggatgaa aaatttgtag attttgttat acacggtcta 88860
gagcatcaat gtcctgctat acttcgacca ttaattaggt tgtttattga tatactatta 88920
tttgttatag taatttatat ttttacggta cgtctagtaa gtagaaatta tcaaatgttg 88980
ttggtggcgc tagtcatcac attaactatt ttttattact ttatactata atagtactag 89040
actgacttct aacaaacatc tcacctgcca taaataaatg cttgatatta aagtcttcta 89100
tttctaacac tattccatct gtggaaaata atactctgac attatcgcta attgacacat 89160
cggtgagtga tatgcctata aagtaataat cttctttggg cacatatacc agtgtaccag 89220
gttctaacaa cctatttact ggtgctcctg tagcatactt tttctttacc ttgagaatat 89280
ccatcgtttg cttggtcaat agcgatatgt gattttttat caaccactcg aaaaagtaat 89340
tggagtgttc atatcctcta cgggctattg tctcatggcc gtgtatgaaa tttaagtaac 89400
acgactgtgg tagatttgtt ctatagagcc gattgccgca aatagataga actaccaata 89460
tgtctgtaca aatgttaaac attaattgat taacagaaaa aacaatgttc gttctgggaa 89520
tagaaaccag atcaaaacaa aattcgttag aatatatgcc acgtttatac atggaatata 89580
aaataactac agtttgaaaa ataacagtat catttaaaca tttaacttgc ggggttaatt 89640
tcacaacttt actgttttta aactgttcaa aatatagcat cgatccgtga gaaatacgtt 89700
tagccgcctt taatagagga aatcccaccg cctttctgga tctcaccaac gacgatagtt 89760
ctgaccagca actcatttct tcatcatcca cctgttttaa catataatag gcaggagata 89820
gatatccgtc attgcaatat tccttctcgt aggcacacaa tctaatattg ataaaatctc 89880
cattctcttc tctgcattta ttatcttgtt tcggtggctg attaggctgt agtcttggtt 89940
taggctttgg tatatcgttg ttgaatctat tttggtcatt aaatctttca tttcttcctg 90000
gtatattttt atcacctcgt ttggttggat ttttgtctat attatcgttt gtaacatcgg 90060
tacgggtatt catttatcac aaaaaaaact tctctaaatg agtctactgc tagaaaacct 90120
catcgaagaa gataccatat tttttgcagg aagtatatct gagtatgatg atttacaaat 90180
ggttattgcc ggcgcaaaat ccaaatttcc aagatctatg ctttctattt ttaatatagt 90240
acctagaacg atgtcaaaat atgagttgga gttgattcat aacgaaaata tcacaggagc 90300
aatgtttacc acaatgtata atataagaaa caatttgggt ctaggagatg ataaactaac 90360
tattgaagcc attgaaaact atttcttgga tcctaacaat gaagttatgc ctcttattat 90420
taataatacg gatatgactg ccgtcattcc taaaaaaagt ggtaggagaa agaataagaa 90480
catggttatc ttccgtcaag gatcatcacc tatcttgtgc attttcgaaa ctcgtaaaaa 90540
gattaatatt tataaagaaa atatggaatc cgcgtcgact gagtatacac ctatcggaga 90600
caacaaggct ttgatatcta aatatgcggg aattaatgtc ctgaatgtgt attctccttc 90660
cacatccata agattgaatg ccatttacgg attcaccaat aaaaataaac tagagaaact 90720
tagtactaat aaggaactag aatcgtatag ttctagccct cttcaagaac ccattaggtt 90780
aaatgatttt ctgggactat tggaatgtgt taaaaaaaat attcctctaa cagatattcc 90840
gacaaaggat tgattactat aaatggagaa tgttcctaat gtatacttta atcctgtgtt 90900
tatagagccc acgtttaaac attctttatt aagtgtttat aaacacagat taatagtttt 90960
atttgaagta ttcgttgtat tcattctaat atatgtattt tttagatctg aattaaatat 91020
gttcttcatg cctaaacgaa aaatacccga tcctattgat agattacgac gtgctaatct 91080
agcgtgtgaa gacgataaat taatgatcta tggattacca tggatgacaa ctcaaacatc 91140
tgcgttatca ataaatagta aaccgatagt gtataaagat tgtgcaaagc ttttgcgatc 91200
aataaatgga tcacaaccag tatctcttaa cgatgttctt cgcagatgat gattcatttt 91260
ttaagtattt ggctagtcaa gatgatgaat cttcattatc tgatatattg caaatcactc 91320
aatatctaga ctttctgtta ttattattga tccaatcaaa aaataaatta gaagccgtgg 91380
gtcattgtta tgaatctctt tcagaggaat acagacaatt gacaaaattc acagactctc 91440
aagattttaa aaaactgttt aacaaggtcc ctattgttac agatggaagg gtcaaactta 91500
ataaaggata tttgttcgac tttgtgatta gtttgatgcg attcaaaaaa gaatcctctc 91560
tagctaccac cgcaatagat cctattagat acatagatcc tcgtcgtgat atcgcatttt 91620
ctaacgtgat ggatatatta aagtcgaata aagtgaacaa taattaattc tttattgtca 91680
tcatgaacgg cggacatatt cagttgataa tcggccccat gttttcaggt aaaagtacag 91740
aattaattag acgagttaga cgttatcaaa tagctcaata taaatgcgtg actataaaat 91800
attctaacga taatagatac ggaacgggac tatggacgca tgataagaat aattttgaag 91860
cattggaagc aactaaacta tgcgatgtct tggaatcaat tacagatttc tccgtgatag 91920
gtatcgatga aggacagttc tttccagaca ttgttgaatt ctgtgagcgt atggcaaacg 91980
aaggaaaaat agttatagta gccgcactcg atgggacatt tcaacgtaaa ccgtttaata 92040
atattttgaa tcttattcca ttatctgaaa tggtggtaaa actaactgct gtgtgtatga 92100
aatgctttaa ggaggcttcc ttttctaaac gattgggtga ggaaaccgag atagaaataa 92160
taggaggtaa tgatatgtat caatcggtgt gtagaaagtg ttacatcgac tcataatatt 92220
atatttttta tctaaaaaac taaaaataaa cattgattaa attttaatat aatacttaaa 92280
aatggatgtt gtgtcgttag ataaaccgtt tatgtatttt gaggaaattg ataatgagtt 92340
agattacgaa ccagaaagtg caaatgaggt cgcaaaaaaa ctgccgtatc aaggacagtt 92400
aaaactatta ctaggagaat tattttttct tagtaagtta cagcgacacg gtatattaga 92460
tggtgccacc gtagtgtata taggatctgc tcccggtaca catatacgtt atttgagaga 92520
tcatttctat aatttaggag tgatcatcaa atggatgcta attgacggcc gccatcatga 92580
tcctatttta aatggattgc gtgatgtgac tctagtgact cggttcgttg atgaggaata 92640
tctacgatcc atcaaaaaac aactgcatcc ttctaagatt attttaattt ctgatgtaag 92700
atccaaacga ggaggaaatg aacctagtac ggcggattta ctaagtaatt acgctctaca 92760
aaatgtcatg attagtattt taaaccccgt ggcatctagt cttaaatgga gatgcccgtt 92820
tccagatcaa tggatcaagg acttttatat cccacacggt aataaaatgt tacaaccttt 92880
tgctccttca tattcagctg aaatgagatt attaagtatt tataccggtg agaacatgag 92940
actgactcga gttaccaaat tagacgctgt aaattatgaa aaaaagatgt actaccttaa 93000
taagatcgtc cgtaacaaag tagttgttaa ctttgattat cctaatcagg aatatgacta 93060
ttttcacatg tactttatgc tgaggaccgt gtactgcaat aaaacatttc ctactactaa 93120
agcaaaggta ctatttctac aacaatctat atttcgtttc ttaaatattc caacaacatc 93180
aactgaaaaa gttagtcatg aaccaataca acgtaaaata tctagcaaaa attctatgtc 93240
taaaaacaga aatagcaaga gatccgtacg cggtaataaa tagaaacgta ctactgagat 93300
atactaccga tatagagtat aatgatttag ttactttaat aaccgttaga cataaaattg 93360
attctatgaa aactgtgttt caggtattta acgaatcatc cataaattat actccggttg 93420
atgatgatta tggagaacca atcattataa catcgtatct tcaaaaaggt cataacaagt 93480
ttcctgtaaa ttttctatac atagatgtgg taatatctga cttatttcct agctttgtta 93540
gactagatac tacagaaact aatatagtta atagtgtact acaaacaggt gatggtaaaa 93600
agactcttcg tcttcccaaa atgttagaga cggaaatagt tgtcaagatt ctctatcgcc 93660
ctaatatacc attaaaaatt gttagatttt tccgcaataa catggtaact ggagtagaga 93720
tagccgatag atctgttatt tcagtcgctg attaatcaat tagtagagat gagataagaa 93780
cattataata atcaataata tatcttatat cttatatctt atatcttata tcttgtttag 93840
aaaaatgcta atattaaaat agctaacgct agtaatccaa tcggaagcca tttgatatct 93900
ataatagggt atctaatttc ctgatttaaa tagcggacag ctatattctc ggtagctact 93960
cgtttggaat cacaaacatt atttacatct aatttactat ctgtaatgga aacgtttccc 94020
aatgaaatgg tacaatccga tacattgcat tttgttatat ttttttttaa agaggctggt 94080
aacaacgcat cgcttcgttt acatggctcg taccaacaat aatagggtaa tcttgtatct 94140
attcctatcc gtactatgct tttatcagga taaatacatt tacatcgtat atcgtctttg 94200
ttagcatcac agaatgcata aatttgttcg tccgtcatga taaaaattta aagtgtaaat 94260
ataactatta tttttatagt tgtaataaaa agggaaattt gattgtatac tttcggttct 94320
ttaaaagaaa ctgacttgat aaaaatggct gtaatctcta aggttacgta tagtctatat 94380
gatcaaaaag agattaatgc tacagatatt attattagtc atgttaaaaa tgacgacgat 94440
atcggtaccg ttaaagatgg taaactaggt gctatggatg gggcattatg taagacttgt 94500
gggaaaacgg aattggaatg tttcggtcac tggggtaaag taagtattta taaaactcat 94560
atagttaagc ctgaatttat ttcagaaatt attcgtttac tgaatcatat atgtattcac 94620
tgcggattat tgcgttcacg agaaccgtat tccgacgata ttaacctaaa agagttatcg 94680
ggacacgctc ttaggagatt aaaggataaa atattatcca agaaaaagtc atgttggaac 94740
agcgaatgta tgcaaccgta tcaaaaaatt actttttcaa agaaaaaggt ttgtttcgtc 94800
aacaagttgg atgatattaa cgttcctaat tctctcatct atcaaaagtt aatttctatt 94860
catgaaaagt tttggccatt attagaaatt catcaatatc cagctaactt attttataca 94920
gactactttc ccatccctcc gttgattatt agaccggcta ttagtttttg gatagatagt 94980
atacccaaag aaaccaatga attaacttac ttattaggta tgatcgttaa gaattgtaac 95040
ttgaatgctg atgaacaggt tatccagaag gcggtaatag aatacgatga tattaaaatt 95100
atttctaata acactaccag tatcaattta tcatatatta catccggcaa aaataatatg 95160
attagaagtt atatcgtcgc ccggcgaaaa gatcagaccg ctagatctgt aattggtccc 95220
agtacatcta tcaccgttaa tgaggtagga atgcccgcat atattagaaa tacacttaca 95280
gaaaagatat ttgttaatgc ctttacagtg gataaagtta aacaactatt agcgtcaaac 95340
caagttaaat tttactttaa taaacgatta aaccaattaa caagaatacg ccaaggaaag 95400
tttattaaaa ataaaataca tttattgcct ggtgattggg tagaagtagc tgttcaagaa 95460
tatacaagta ttatttttgg aagacagccg tctctacata gatacaacgt catcgcttca 95520
tctatcagag ctaccgaagg agatactatc aaaatatctc ccggaattgc caactctcaa 95580
aatgctgatt tcgacgggga tgaggaatgg atgatattag aacaaaatcc taaagctgta 95640
attgaacaaa gtattcttat gtatccgacg acgttactca aacacgatat tcatggagcc 95700
cccgtttatg gatctattca agatgaaatc gtagcagcgt attcattgtt taggatacaa 95760
gatctttgtt tagatgaagt attgaacatc ttggggaaat atggaagaga gttcgatcct 95820
aaaggtaaat gtaaattcag cggtaaagat atctatactt acttgatagg tgaaaagatt 95880
aattatccgg gtctcttaaa ggatggtgaa attattgcaa acgacgtaga tagtaatttt 95940
gttgtggcta tgaggcatct gtcattggct ggactcttat ccgatcataa gtcgaacgtg 96000
gaaggtatca actttattat caagtcatct tatgttttta agagatatct atctatttac 96060
ggttttgggg tgacattcaa agatctgaga ccaaattcga cgttcactaa taaattggag 96120
gccatcaacg tagaaaaaat agaacttatc aaagaagcat acgccaaata tctcaacgat 96180
gtaagagacg ggaaaatagt tccattatct aaagctttag aggcggacta tgtggaatcc 96240
atgttatcca acttgacaaa tcttaatatc cgagagatag aagaacatat gagacaaacg 96300
ctgatagatg atccagataa taacctcctg aaaatggcca aagcgggtta taaagtaaat 96360
cctacagaac taatgtatat tctaggtacg tatggacaac aaaggattga tggtgaacca 96420
gcagagactc gagtattggg tagagtttta ccttactatc ttccagactc taaggatcca 96480
gaaggaagag gttacattct taattcttta acaaaaggat taacgggttc tcaatattac 96540
ttttcgatgc tggttgccag atctcaatct actgatatcg tctgtgaaac atcacgtacc 96600
ggaacactgg ctagaaaaat cattaaaaag atggaggata tggtggtcga cggatacgga 96660
caagtagtta taggtaatac gctcatcaag tacgccgcca attataccaa aattctaggc 96720
tcagtatgta aacctgtaga tcttatctat ccagatgagt ccatgacttg gtatttggaa 96780
attagtgctc tgtggaataa aataaaacag ggattcgttt actctcagaa acagaaactt 96840
gcaaagaaga cattggcgcc gtttaatttc ctagtattcg tcaaacccac cactgaggat 96900
aatgctatta aggttaagga tctgtacgat atgattcata acgtcattga tgatgtgaga 96960
gagaaatact tctttacggt atctaatata gattttatgg agtatatatt cttgacgcat 97020
cttaatcctt ctagaattag aattacaaaa gaaacggcta tcactatctt tgaaaagttc 97080
tatgaaaaac tcaattatac tctaggtggt ggaactccta ttggaattat ttctgcacag 97140
gtattgtctg agaagtttac acaacaagcc ctgtccagtt ttcacactac tgaaaaaagt 97200
ggtgccgtca aacaaaaact tggtttcaac gagtttaata acttgactaa tttgagtaag 97260
aataagaccg aaattatcac tctggtatcc gatgatatct ctaaacttca atctgttaag 97320
attaatttcg aatttgtatg tttgggagaa ttaaatccag acatcactct tcgaaaagaa 97380
acagataggt atgtagtaga tataatagtc aatagattat acatcaagag agcagaaatt 97440
accgaattag tcgtcgaata tatgattgaa cgatttatct cctttagcgt cattgtaaag 97500
gaatggggta tggaaacatt cattgaggat gaggataata ttagatttac tgtctatcta 97560
aatttcgttg aaccagagga attgaatctt agtaagttta tgatggttct tccgggtgcc 97620
gccaacaagg gcaagattag taaattcaag attcctatct ctgattatac gggttatgac 97680
gacttcaatc aaacaaaaaa gctcaataag atgactgtag aactcatgaa tctaaaagaa 97740
ttgggttctt tcgatttgga aaacgtcaac gtgtatcctg gagtatggaa tacatacgat 97800
atcttcggta tcgaggccgc tcgtgaatac ttgtgcgaag ccatgttaaa cacctatgga 97860
gaagggttcg attatctgta tcagccttgt gatcttctcg ctagtttact atgtgctagt 97920
tacgaaccag aatcagtgaa taaattcaag ttcggcgcag ctagtactct taagagagct 97980
acgttcggag acaataaagc attgttaaac gcggctcttc ataaaaagtc agaacctatt 98040
aacgataata gtagctgcca cttttttagc aaggtcccta atataggaac tggatattac 98100
aaatacttta tcgacttggg tcttctcatg agaatggaaa ggaaactatc tgataagata 98160
tcttctcaaa agatcaagga aatggaagaa acagaagact tttaattctt atcaataaca 98220
tatttttcta tgatctgtct tttaaacgat ggattttcca caaatgcgcc tctcaagtcc 98280
ctcatagaat gatacacgta taaaaaatat agcataggca atgactcctt atttttagac 98340
attagatatg ccaaaatcat agccccgctt ctatttactc ccgcagcaca atgaaccaac 98400
acgggctcgt ttcgttgatc acatttagat aaaaaggcgg ttacgtcgtc aaaatattta 98460
ctaatatcgg tagttgtatc atctaccaac ggtatatgaa taatattaat attagagtta 98520
ggtaatgtat atttatccat cgtcaaattt aaaacatatt tgaacttaac ttcagatgat 98580
ggtgcatcca tagcattttt ataatttccc aaatacacat tattggttac tcttgtcatt 98640
atagtgggag atttggcttt gtgcatatct ccagttgaac gtagtagtaa gtatttatac 98700
aaacttttct tatccattta taacgtacaa atggataaaa ctactttatc ggtaaacgcg 98760
tgtaatttag aatacgttag agaaaaggct atagtaggcg tacaagcagc caaaacatca 98820
acacttatat tctttgttat tatattggca attagtgcgc tattactctg gtttcagacg 98880
tctgataatc cagtctttaa tgaattaacg agatatatgc gaattaaaaa tacggttaac 98940
gattggaaat cattaacgga tagcaaaaca aaattagaaa gtgatagagg tagacttcta 99000
gccgctggta aggatgatat attcgacttc aaatgtgtgg atttcggcgc ctattttata 99060
gctatgcgat tggataagaa aacatatctg ccgcaagcta ttaggcgagg tactggagac 99120
gcgtggatgg ttaaaaaggc ggcaaaggtc gatccatctg ctcaacaatt ttgtcagtat 99180
ttgataaaac acaagtctaa taatgttatt acttgtggta atgagatgtt aaatgaatta 99240
ggttatagcg gttattttat gttaccgcat tggtgttccg attttagtaa tatggaatag 99300
tgttagataa atgcggtaac aaatgttcct gtaaggaacc ataacagttt agatttaacg 99360
ttaaagatga gcataaacat aataaacaaa attacaatca aacctataac attaatatca 99420
aacaatccaa aaaatgaaat cagtggagta gtaaacgcgt acataactcc tggataacgt 99480
ttagcagctg ccgttcctat tctagaccaa aaattcggtt tcatgttttc gaaacggtat 99540
tctgcaacaa gtcgaggatc gtgttctaca tatttggcgg cgttatccag tatctgccta 99600
ttgatcttca tttcgttttc gattctggct atttcaaaat aaaatcccga tgatagacct 99660
ccagacttta taatttcatc tacgatgttc agcgccgtag taactctaat aatataggct 99720
gataagctaa catcataccc tcctgtatat gtgaatatgg catgattttt gtccattaca 99780
agctcggttt taactttatt gcctgtaata atttctctca tctgtaggat atctattttt 99840
ttgtcatgca ttgccttcaa gacgggacga agaaacgtaa tatcctcaat aacgttatcg 99900
ttttctacaa taactacata ttctaccttt ttattttcta actcagtaaa aaaattagaa 99960
tcccataggg ctaaatgtct agcgatattt cttttcgttt cctctgtaca catagtgtta 100020
caaaaccctg aaaagaagtg agtatacttg tcatcatttc taatgtttcc tccagtccac 100080
tgtataaacg cataatcctt gtaatgatct ggatcatcct tgactaccac aacatttctt 100140
ttttctggca taacttcgtt gtcctttaca tcatcgaact tctgatcatt aatatgctca 100200
tgaacattag gaaatgtttc tgatggaggt ctatcaataa ctggcacaac aataacagga 100260
gttttcaccg ccgccattta gttattgaaa ttaatcatat acaactcttt aatacgagtt 100320
atattttcgt ctatccattg tttcacattg acatatttcg acaaaaagat ataaaatgcg 100380
tattccaatg cttctctgtt taatgaatta ctaaaatata caaacacgtc actgtctggc 100440
aataaatgat atcttagaat attgtaacaa tttattttgt attgcacatg ttcgtgatct 100500
atgagttctt cttcgaatgg cataggatct ccgaatctga aaacgtataa ataggagtta 100560
gaataataat atttgagagt attggtaata tataaactct ttagcggtat aattagtttt 100620
tttctctcaa tttctatttt tagatgtgat ggaaaaatga ctaattttgt agcattagta 100680
tcatgaactc taatcaaaat cttaatatct tcgtcacacg ttagctcttt gaagttttta 100740
agagatgcat cagttggttc tacagatgga gtaggtgcaa caattttttg ttctacacat 100800
gtatgtactg gagccattgt tttaactata atggtgcttg tatcgaaaaa ctttaatgca 100860
gatagcggaa gctcttcgcc gcgactttct acatcgtaat tgggttctaa cgccgatctc 100920
tgaatggata ctagttttct aagttctaat gtgattctct gaaaatgtaa atccaattcc 100980
tccggcatta tagatgtgta tacatcggta aataaaacta tagtatccaa cgatcccttc 101040
tcgcaaattc tagtcttaac caaaaaatcg tatataacca cggagatggc gtatttaaga 101100
gtggattctt ctaccgtttt gttcttggat gtcatatagg aaactataaa gtccgcacta 101160
ctgttaagaa tgattactaa cgcaactata tagtttaaat taagcatttt ggaaacataa 101220
aataactctg tagacgatac ttgactttcg aataagtttg cagacaaacg aagaaagaac 101280
agacctctct taatttcaga agaaaacttt ttttcgtatt cctgacgtct agagtttata 101340
tcaataagaa agttaagaat tagtcggtta atgttgtatt tcattaccca agtttgagat 101400
ttcataatat tatcaaaaga catgataata ttaaagataa agcgctgact atgaacgaaa 101460
tagctatatg gttcgctcaa gaatatagtc ttgttaaacg tggaaacgat aactgtattt 101520
ttaatcacgt cagcggcatc taaattaaat ataggtatat ttattccaca cactctacaa 101580
tatgccacac catcttcata ataaataaat tcgttagcaa aattattaat tttagtgaaa 101640
tagttagcgt caactttcat agcttccttc aatctaattt gatgctcaca cggtgcgaat 101700
tccactctaa catccctttt ccatgcctca ggttcatcga tctctataat atctagtttt 101760
ttgcgtttca caaacacagg ctcgtctctc gcgatgagat ctgtatagta actatgtaaa 101820
tgataactag atagaaagat gtagctatat agatgacgat cctttaagag aggtataata 101880
actttacccc aatcagatag actgttgtta tggtcttcgg aaaaagaatt tttataaatt 101940
tttccagtat tttccaaata tacgtactta acatctaaaa aatccttaat gataatagga 102000
atggataatc cgtctatttt ataaagaaat acatatcgca cattatactt ttttttggaa 102060
atgggaatac cgatgtgtct acataaatat gcaaagtcta aatatttttt agagaatctt 102120
agttggtcca aattcttttc caagtacggt aatagatttt tcatattgaa cggtatcttc 102180
ttaatctctg gttctagttc cgcattaaat gatgaaacta agtcactatt tttataacta 102240
acgattacat cacctctaac atcatcattt accagaatac tgatcttctt ttgtcgtaaa 102300
tacatgtcta atgtgttaaa aaaaagatca tacaagttat acgtcatttc atctgtggta 102360
ttcttgtcat tgaaggataa actcgtacta atctcttctt taacagcctg ttcaaattta 102420
tatcctatat acgaaaaaat agcaaccagt gtttgatcat ccgcgtcaat attctgttct 102480
atcgtagtgt ataacaatcg tatatcttct tctgtgatag tcgatacgtt ataaaggttg 102540
ataacgaaaa tatttttatt ttgtgaaata aagtcatcgt aggattttgg acttatattc 102600
gcgtctagta gatatgcttt tatttttgga atgatctcaa ttagaatagt ctctttagag 102660
tccatttaaa gttacaaaca actaggaaat tggtttatga tgtataattt ttttagtttt 102720
tatagattct ttattctata cttaaaaaat gaaaataaat acaaaggttc ttgagggttg 102780
tgttaaattg aaagcgagaa ataatcataa attatttcat tatcgcgata tccgttaagt 102840
ttgtatcgta atggcgtggt caattacgaa taaagcggat actagtagtt tcacaaagat 102900
ggctgaaatc agagctcatc taaaaaatag cgctgaaaat aaagataaaa acgaggatat 102960
tttcccggaa gatgtaataa ttccatctac taagcccaaa accaaacgag ccactactcc 103020
tcgtaaacca gcggctacta aaagatcaac caaaaaggag gaagtggaag aagaagtagt 103080
tatagaggaa tatcatcaaa caactgaaaa aaattctcca tctcctggag tcagcgacat 103140
tgtagaaagc gtggccgctg tagagctcga tgatagcgac ggggatgatg aacctatggt 103200
acaagttgaa gctggtaaag taaatcatag tgctagaagc gatctttctg acctaaaggt 103260
ggctaccgac aatatcgtta aagatcttaa gaaaattatt actagaatct ctgcagtatc 103320
gacggttcta gaggatgttc aagcagctgg tatctctaga caatttactt ctatgactaa 103380
agctattaca acactatctg atctagtcac cgagggaaaa tctaaagttg ttcgtaaaaa 103440
agttaaaact tgtaagaagt aaatgcgtgc acttttttat aaagatggta aactctttac 103500
cgataataat tttttaaatc ctgtatcaga cgataatcca gcgtatgagg ttttgcaaca 103560
tgttaaaatt cctactcatt taacagatgt agtagtatat gaacaaacgt gggaggaggc 103620
gttaactaga ttaatttttg tgggaagcga ttcaaaagga cgtagacaat acttttacgg 103680
aaaaatgcat gtacagaatc gcaacgctaa aagagatcgt atttttgtta gagtatataa 103740
cgttatgaaa cgaattaatt gttttataaa caaaaatata aagaaatcgt ccacagattc 103800
caattatcag ttggcggttt ttatgttaat ggaaactatg ttttttatta gatttggtaa 103860
aatgaaatat cttaaggaga atgaaacagt agggttatta acactaaaaa ataaacacat 103920
agaaataagt cccgatgaaa tagttatcaa gtttgtagga aaggacaaag tttcacatga 103980
atttgttgtt cataagtcta atagactata taaaccgcta ttgaaactga cggatgattc 104040
tagtcccgaa gaatttctgt tcaacaaact aagtgaacga aaggtatacg aatgtatcaa 104100
acagtttggt attagaatca aggatctccg aacgtatgga gtcaattata cgtttttata 104160
taatttttgg acaaatgtaa agtccatatc tcctcttccg tcaccaaaaa agttaatagc 104220
attaactatc aaacaaactg ctgaagttgt aggtcatact ccatcaattt caaaaagagc 104280
ttatatggca acgactattt tagaaatggt aaaggataaa aattttttag atgtagtatc 104340
taaaactacg ttcgatgaat tcctatctat agtcgtagat cacgttaaat catctacgga 104400
tggatgatat agatctttac acaaataatt acaagaccga taaatggaaa tggataagcg 104460
tatgaaatct ctcgcaatga cagctttctt cggagagcta aacacattag atattatggc 104520
attgataatg tctatattta aacgccatcc aaacaatacc attttttcag tggataagga 104580
tggtcagttt atgattgatt tcgaatacga taattataag gcttctcaat atttggatct 104640
gaccctcact ccgatatctg gagatgaatg caagactcac gcatcgagta tagccgaaca 104700
attggcgtgt gcggatatta ttaaagagga tattagcgaa tacatcaaaa ctactccccg 104760
tcttaaacga tttataaaaa aataccgcaa tagatcagat actcgcatca gtcgagatac 104820
agaaaagctt aaaatagctc tagctaaagg catagattac gaatatataa aagacgcttg 104880
ttaataagta aatgaaaaaa aactagtcgt ttataataaa acacgatatg gatgccaacg 104940
tagtatcatc ttctactatt gcgacgtata tagacgcttt agcgaagaat gcttcagaat 105000
tagaacagag gtctaccgca tacgaaataa ataatgaatt ggaactagta tttattaagc 105060
cgccattgat tactttgaca aatgtagtga atatctctac gattcaggaa tcgtttattc 105120
gatttaccgt tactaataag gaaggtgtta aaattagaac taagattcca ttatctaagg 105180
tacatggtct agatgtaaaa aatgtacagt tagtagatgc tatagataac atagtttggg 105240
aaaagaaatc attagtgacg gaaaatcgtc ttcacaaaga atgcttgttg agactatcga 105300
cagaggaacg tcatatattt ttggattaca agaaatatgg atcctctatc cgactagaat 105360
tagtcaatct tattcaagca aaaacaaaaa actttacgat agactttaag ctaaaatatt 105420
ttctaggatc cggtgcccag tctaaaagtt ctttattaca cgctattaat catccaaagt 105480
caaggcctaa tacatctctg gaaatagaat tcacacctag agacaatgaa acagttccat 105540
atgatgaact aataaaggaa ttgacgactc tatcacgtca tatatttatg gcttctccag 105600
agaatgtaat tctttctccg cctattaacg cgcctataaa aacctttatg ttgcctaaac 105660
aagatatagt aggtttggat ctggaaaatc tatatgccgt aactaagact gacggcattc 105720
ctataactat cagagttaca tcaaacgggt tgtattgtta ttttacacat cttgggtata 105780
ttattagata tccagttaag agaataatag attccgaagt agtagtcttt ggtgaggcag 105840
ttaaggataa gaactggacc gtatatctta ttaagctaat agagcctgtg aatgctatca 105900
gtgatagact agaagaaagt aagtatgttg aatctaaact agtggatatt tgtgatcgga 105960
tagtattcaa gtcaaagaaa tacgaaggtc cgtttactac aactagtgaa gtcgtcgata 106020
tgttatctac atatttacca aagcaaccag aaggtgttat tctgttctat tcaaagggac 106080
ctaaatctaa cattgatttt aaaattaaaa aggaaaatac tatagaccaa actgcaaatg 106140
tagtatttag gtacatgtcc agtgaaccaa ttatctttgg agaatcgtct atctttgtag 106200
agtataagaa atttagcaac gataaaggct ttcctaaaga atatggttct ggtaagattg 106260
tgttatataa cggcgttaat tatctaaata atatctattg tttggaatat attaatacac 106320
ataatgaagt gggtattaag tccgtggttg tacctattaa gtttatagca gaattcttag 106380
ttaatggaga aatacttaaa cctagaattg ataaaaccat gaaatatatt aactcagaag 106440
attattatgg aaatcaacat aatatcatag tcgaacattt aagagatcaa agcatcaaaa 106500
taggagatat ctttaacgag gataaactat cggatgtggg acatcaatac gccaataatg 106560
ataaatttag attaaatcca gaagttagtt attttacgaa taaacgaact agaggaccgt 106620
tgggaatttt atcaaactac gtcaagactc ttcttatttc tatgtattgt tccaaaacat 106680
ttttagacga ttccaacaaa cgaaaggtat tggcgattga ttttggaaac ggtgctgacc 106740
tggaaaaata cttttatgga gagattgcgt tattggtagc gacggatccg gatgctgatg 106800
ctatagctag aggaaatgaa agatacaaca aattaaactc tggaattaaa accaagtact 106860
acaaatttga ctacattcag gaaactattc gatccgatac atttgtctct agtgtcagag 106920
aagtattcta ttttggaaag tttaatatca tcgactggca gtttgctatc cattattctt 106980
ttcatccgag acattatgct accgtcatga ataacttatc cgaactaact gcttctggag 107040
gcaaggtatt aatcactacc atggacggag acaaattatc aaaattaaca gataaaaaga 107100
cttttataat tcataagaat ttacctagta gcgaaaacta tatgtctgta gaaaaaatag 107160
ctgatgatag aatagtggta tataatccat caacaatgtc tactccaatg actgaataca 107220
ttatcaaaaa gaacgatata gtcagagtgt ttaacgaata cggatttgtt cttgtagata 107280
acgttgattt cgctacaatt atagaacgaa gtaaaaagtt tattaatggc gcatctacaa 107340
tggaagatag accgtctaca aaaaactttt tcgaactaaa tagaggagcc attaaatgtg 107400
aaggtttaga tgtcgaagac ttacttagtt actatgttgt ttatgtcttt tctaagcggt 107460
aaataataat atggtatggg ttctgatatc cccgttctaa atgcattaaa taattccaat 107520
agagcgattt ttgttcctat aggaccttcc aactgtggat actctgtatt gttaatagat 107580
atattaatac ttttgtcggg taacagaggt tctacgtctt ctaaaaataa aagttttata 107640
acatctggcc tgttcataaa taaaaacttg gcgattctat atatactctt attatcaaat 107700
ctagccattg tcttatagat gtgagctact gtaggtgtac catttgattt tctttctaat 107760
actatatatt tctctcgaag aagttcttgc acatcatctg ggaataaaat actactgttg 107820
agtaaatcag ttattttttt tatatcgata ttgatggaca tttttatagt taaggataat 107880
aagtatccca aagtcgataa cgacgataac gaagtattta tacttttagg aaatcacaat 107940
gactttatca gattaaaatt aacaaaatta aaggagcatg tatttttttc tgaatatatt 108000
gtgactccag atacatatgg atctttatgc gtcgaattaa atgggtctag ttttcagcac 108060
ggtggtagat atatagaggt ggaggaattt atagatgctg gaagacaagt tagatggtgt 108120
tctacatcca atcatatatc taaagatata cccgaagata tgcacactga taaatttgtc 108180
atttatgata tatacacttt tgacgctttc aagaataaac gattggtatt cgtacaggtg 108240
cctccgtcgt taggagatga tagtcatttg actaatccgt tattgtcacc gtattatcgt 108300
aattcagtag ccagacaaat ggtcaatgat atgattttta atcaagattc atttttaaaa 108360
tatttattag aacatctgat tagaagccac tatagagttt ctaaacatat aacaatagtt 108420
agatacaagg ataccgaaga attaaatcta acgagaatat gttataatag agataagttt 108480
aaggcgtttg tattcgcttg gtttaacggc gtttcggaaa atgaaaaggt actagatacg 108540
tataaaaagg tatctaattt gatataatga attcagtgac tgtatcacac gcgccatata 108600
ctattactta tcacgatgat tgggaaccag taatgagtca attggtagag ttttataacg 108660
aagtagccag ttggctgcta cgagacgaga cgtcgcctat tcctgataag ttctttatac 108720
agttgaaaca accgcttaga aataaacgag tatgtgtgtg tggtatagat ccgtatccga 108780
aagatggaac tggtgtaccg ttcgaatcac caaattttac aaaaaaatca attaaggaga 108840
tagcttcatc tatatctaga ttaaccggag taattgatta taaaggttat aaccttaata 108900
taatagacgg ggttataccc tggaattatt acttaagttg taaattagga gaaacaaaaa 108960
gtcacgcgat ttactgggat aaaatttcta agttactgct gcagcatata actaaacacg 109020
ttagtgttct ttattgtttg ggtaaaacag atttctcgaa tatacgggcc aagttagaat 109080
ccccggtaac taccatagtc ggatatcatc cagcggctag agaccgccaa ttcgagaaag 109140
atagatcatt tgaaattatc aacgttttac tggaattaga caacaaggca cctataaatt 109200
gggctcaagg gtttatttat taatgcttta gtgaaatttt aacttgtgtt ctaaatggat 109260
gcggctatta gaggtaataa tgttatcttt gttcttaaga ctataggtgt cccgtcagcg 109320
tgcagacaaa atgaagatcc aagatttgta gaagcattta aatgcgacga gttagaaaga 109380
tatattgaga ataatccaga atgtacacta ttcgaaagtc ttagggatga ggaagcatac 109440
tctatagtca gaattttcat ggatgtagat ttagacgcgt gtctagacga aatagattat 109500
ttaacggcta ttcaagattt tattatcgag gtgtcaaact gtgtagctag attcgcgttt 109560
acagaatgcg gcgccattca tgaaaatgta ataaaatcca tgagatctaa tttttcattg 109620
actaagtcta caaatagaga taaaacaagt tttcatatta tctttttaga cacgtatacc 109680
actatggata cattgatagc tatgaaacga acactattag aattaagtag atcatctgaa 109740
aatccactaa ccagatcgat agacactgcc gtatatagga gaaaaacaac tcttcgggtt 109800
gtaggtacta ggaaaaatcc aaattgcgac actattcatg taatgcaacc accgcatgat 109860
aatatagaag attacctatt cacttacgtg gatatgaaca acaatagtta ttacttttct 109920
ctacaacgac gattggagga tttagttcct gataagttat gggaaccagg gtttatttca 109980
ttcgaagacg ctataaaaag agtttcaaaa atattcatta attctataat aaactttaat 110040
gatctcgatg aaaataattt tacaacggta ccactggtca tagattacgt aacaccttgt 110100
gcattatgta aaaaacgatc gcataaacat ccgcatcaac tatcgttgga aaatggtgct 110160
attagaattt acaaaactgg taatccacat agttgtaaag ttaaaattgt tccgttggat 110220
ggtaataaac tgtttaatat tgcacaaaga attttagaca ctaactctgt tttattaacc 110280
gaacgaggag accatatagt ttggattaat aattcatgga aatttaacag cgaagaaccc 110340
ttgataacaa aactaatttt gtcaataaga catcaactac ctaaggaata ttcaagcgaa 110400
ttactctgtc caagaaaacg aaagactgta gaagctaaca tacgagacat gttagtagat 110460
tcagtagaga ccgataccta tccggataaa cttccgttta aaaatggtgt attggacctg 110520
gtagacggaa tgttttactc tggagatgat gctaaaaaat atacgtgtac tgtatcaacc 110580
ggatttaaat ttgacgatac aaagttcgtc gaagacagtc cagaaatgga agagttaatg 110640
aatatcatta acgatatcca accattaacg gatgaaaata agaaaaatag agagctatat 110700
gaaaaaacat tatctagttg tttatgtggt gctaccaaag gatgtttaac attctttttt 110760
ggagaaactg caactggaaa gtcgacaacc aaacgtttgt taaagtctgc tatcggtgac 110820
ctgtttgttg agacgggtca aacaatttta acagatgtat tggataaagg acctaatcca 110880
tttatcgcta acatgcattt gaaaagatct gtattctgta gcgaactacc tgattttgcc 110940
tgtagtggat caaagaaaat tagatctgac aatattaaaa agttgacaga accttgtgtc 111000
attggaagac cgtgtttctc caataaaatt aataatagaa accatgcgac aatcattatc 111060
gatactaatt acaaacctgt ctttgatagg atagataacg cattaatgag aagaattgcc 111120
gtcgtgcgat tcagaacaca cttttctcaa ccttctggta gagaggctgc tgaaaataat 111180
gacgcgtacg ataaagtcaa actattagac gaggggttag atggtaaaat acaaaataat 111240
agatatagat ttgcatttct atacttgttg gtgaaatggt acagaaaata tcatgttcct 111300
attatgaaac tatatcctac accggaagag attcctgact ttgcattcta tctcaaaata 111360
ggtactctgt tagtatctag ctctgtaaag catattccat taatgacgga cctctccaaa 111420
aagggatata tattgtacga taatgtggtc actcttccgt tgactacttt ccaacagaaa 111480
atatccaagt attttaattc tagactattt ggacacgata tagagagctt catcaataga 111540
cataagaaat ttgccaatgt tagtgatgaa tatctgcaat atatattcat agaggatatt 111600
tcatctccgt aaatatatgc tcatatattt atagaagata tcacatatct aaatgaatac 111660
cggaatcata gatttatttg ataatcatgt tgatagtata ccaactatat tacctcatca 111720
gttagctact ctagattatc tagttagaac tatcatagat gagaacagaa gcgtgttatt 111780
gttccatatt atgggatcag gtaaaacaat aatcgctttg ttgttcgcct tggtagcttc 111840
cagatttaaa aaggtttaca ttctagtgcc gaacatcaac atcttaaaaa ttttcaatta 111900
taatatgggt gtagctatga acttgtttaa tgacgaattc atagctgaaa atatctttat 111960
tcattccaca acaagttttt attctcttaa ttataacgat aacgtcatta attataacgg 112020
attatctcgc tacaataact ctatttttat cgttgatgag gcacataata tctttgggaa 112080
taatactgga gaacttatga ccgtgataaa aaataaaaac aagattcctt ttttactatt 112140
gtctggatct cccattacta acacacctaa tactctgggt catattatag atttaatgtc 112200
cgaagagacg atagattttg gtgaaattat tagtcgtggt aagaaagtaa ttcagacact 112260
tcttaacgaa cgaggtgtga atgtacttaa ggatttgctt aaaggaagaa tatcatatta 112320
cgaaatgcct gataaagatc taccaacgat aagatatcac ggacgtaagt ttctagatac 112380
tagagtagta tattgtcaca tgtctaaact tcaagagaga gattatatga ttactagacg 112440
acagctatgt tatcatgaaa tgtttgataa aaatatgtat aacgtgtcaa tggcagtatt 112500
gggacaactt aatctgatga ataatttaga tactttattt caggaacagg ataaggaatt 112560
gtacccaaat ctgaaaataa ataatggcgt gttatacgga gaagaattgg taacgttaaa 112620
cattagttcc aaatttaagt actttattaa tcggatacag acactcaacg gaaaacattt 112680
tatatacttt tctaattcta catatggcgg attggtaatt aaatatatca tgctcagtaa 112740
tggatattct gaatataatg gttctcaggg aactaatcca catatgataa acggcaaacc 112800
aaaaacattt gctatcgtta ctagtaaaat gaaatcgtct ttagaggatc tattagatgt 112860
gtataattct cctgaaaacg atgatggtag tcaattgatg tttttgtttt cgtcaaacat 112920
tatgtccgaa tcctatactc tgaaagaggt aaggcatatt tggtttatga ctatcccaga 112980
tactttttct caatacaacc aaattcttgg acgatctatt agaaaattct cttacgccga 113040
tatttctgaa ccagttaatg tatatctttt agccgccgta tattccgatt tcaatgacga 113100
agtgacgtca ttaaacgatt acacacagga tgaattaatt aatgttttac catttgacat 113160
caaaaagctg ttatatctaa aatttaagac gaaagaaacg aatagaatat actctattct 113220
tcaagagatg tctgaaacgt attctcttcc accacatcca tcaattgtaa aagttttatt 113280
gggagaattg gtcagacaat ttttttataa taattctcgt attaagtata acgataccaa 113340
gttacttaaa atggttacat cagttataaa aaataaagaa gacgctagga attacataga 113400
tgatattgta aacggtcact tctttgtatc gaataaagta tttgataaat ctcttttata 113460
caaatacgaa aacgatatta ttacagtacc gtttagactt tcctacgaac catttgtttg 113520
gggagttaac tttcgtaaag aatataacgt ggtatcttct ccataaaact gatgagatat 113580
ataaagaaat aaatgtcgag ctttgttacc aatggatacc tttccgttac attggaacct 113640
catgagctga cgttagacat aaaaactaat attaggaatg ccgtatataa gacgtatctc 113700
catagagaaa ttagtggtaa aatggccaag aaaatagaaa ttcgtgaaga cgtggaatta 113760
cctctcggcg aaatagttaa taattctgta gttataaacg ttccgtgtgt aataacctac 113820
gcgtattatc acgttgggga tatagtcaga ggaacattaa acatcgaaga tgaatcaaat 113880
gtaactattc aatgtggaga tttaatctgt aaactaagta gagattcggg tactgtatca 113940
tttagcgatt caaagtactg cttttttcga aatggtaatg cgtatgacaa tggcagcgaa 114000
gtcactgccg ttctaatgga ggctcaacaa ggtatcgaat ctagttttgt ttttctcgcg 114060
aatatcgtcg actcataaga aagagaatag cggtaagtat aaacacgaat actatggcaa 114120
taattgcgaa tgttttattc tcttcgatat atttttgata atatgaaaaa catgtctctc 114180
tcaaatcgga caaccatctc ataaaatagt tatctcgcgc tggcgaggtg gttgctgctc 114240
gtataatctc cccagaataa tatacttgcg tgtcgtcgtt caatttatac ggatttctat 114300
agttctctgt tatataatgc ggttttctat catgattaga cgacgacaat agtgttctaa 114360
atttagatag ttgatcagaa tgaatgttta ttggcgttgg aaaaattatc catacagcgt 114420
ctgcagagtg gttgatagtt gttcctagat atgtaaaata atccaactta ctaggcagca 114480
aattgtctag ataaaatact gaatcaaacg gtgcagacgt attggcggat ctaatggaat 114540
ccaattgatt aactatcttt tgaaaatata catttttatg atccaatact tgtaagaata 114600
tagaaataat gataagtcca tcatcgtgtt tttttgcctc ttcataagaa ctatattttt 114660
tcttattcca atgaacaaga ttaatctctc cagagtattt gtacacatct atcaagtgat 114720
tggatccata atcgtcttcc tttccccaat atatatgtag tgatgataac acatattcat 114780
tggggagaaa ccctccactt atatatcctc ctttaaaatt aatccttact agttttccag 114840
tgttctggat agtggttggt ttcgactcat tataatgtat gtctaacggc ttcaatcgcg 114900
cgttagaaat tgctttttta gtttctatat taataggaga tagttgttgc ggcatagtaa 114960
aaatgaaatg ataactgttt aaaaatagct cttagtatgg gaattacaat ggatgaggaa 115020
gtgatatttg aaactcctag agaattaata tctattaaac gaataaaaga tattccaaga 115080
tcaaaagaca cgcatgtgtt tgctgcgtgt ataacaagtg acggatatcc gttaatagga 115140
gctagaagaa cttcattcgc gttccaggcg atattatctc aacaaaattc agattctatc 115200
tttagagtat ccactaaact attacggttt atgtactaca atgaactaag agaaatcttt 115260
agacggttga gaaaaggttc tatcaacaat atcgatcctc actttgaaga gttaatatta 115320
ttgggtggta aactagataa aaaggaatct attaaagatt gtttaagaag agaattaaaa 115380
gaggaaagtg atgaacgtat aacagtaaaa gaatttggaa atgtaattct aaaacttaca 115440
acacgggata aattatttaa taaagtatat ataagttatt gcatggcgtg ttttattaat 115500
caatcgttgg aggatttatc gcatactagt atttacaatg tagaaattag aaagattaaa 115560
tcattaaatg attgtattaa cgacgataaa tacgaatatc tgtcttatat ttataatatg 115620
ctagttaata gtaaatgaac ttttacagat ctagtataat tagtcagatt attaagtata 115680
atagacgact agctaagtct attatttgcg aggatgactc tcaaattatc acactcacgg 115740
cattcgttaa ccaatgccta tggtgtcata aacgagtatc cgtgtccgct attttattaa 115800
ctactgataa caaaatatta gtatgtaaca gacgagatag ttttctctat tctgaaataa 115860
ttagaactag aaacatgttt agaaagaaac gattatttct gaattattcc aattatttga 115920
acaaacagga aagaagtata ctatcgtcat ttttttctct agatccagct actactgata 115980
atgatagaat agacgctatt tatccgggtg gcatacccaa aaggggtgag aatgttccag 116040
agtgtttatc cagggaaatt aaagaagaag ttaatataga caattctttt gtattcatag 116100
acactcggtt ttttattcat ggcatcatag aagataccat tattaataaa ttttttgagg 116160
taatcttctt tgtcggaaga atatctctaa cgagtgatca aatcattgat acatttaaaa 116220
gtaatcatga aatcaaggat ctaatatttt tagatccgaa ttcaggtaat ggactccaat 116280
acgaaattgc aaaatatgct ctagatactg caaaacttaa atgttacggc catagaggat 116340
gttattacga atcattaaaa aaattaactg aggatgattg attagaaaat ataaattaat 116400
ttaccatcgt gtatttttat aacgggattg tccggcatat catgtagata gttaccgtct 116460
acatcgtata ctcgaccatc tacgccttta aatcctctat ttattgacat taatctatta 116520
gaattggaat accaaatatt agtaccctca attagtttat tggtaatatt ttttttagac 116580
gatagatcga tggctcttga aaccaaggtt ttccaaccgg actcattgtc gatcggtgag 116640
aagtcttttt cattagcatg aatccattct aatgatgtat gtttaaacac tctaaacaat 116700
tggacaaatt cttttgattt gctttgaatg atttcaaata ggtcttcgtc tacagtaggc 116760
ataccattag ataatctagc cattataaag tgcacgttta catatctacg ttctggagga 116820
gtaagaacgt gactattgag acgaatggct cttcctacta tctgacgaag agacgcctcg 116880
ttccatgtca tatctaaaat gaagatatca ttaattgaga aaaaactaat accctcgcct 116940
ccactagaag agaatacgca tgttttaatg cattctccgt tagtgtttga ttcttggtta 117000
aactcagcca ccgccttgat tctagtatct tttgttctag atgagaactc tatattagag 117060
ataccaaaga ctttgaaata tagtaataag atttctattc ctgactgatt aacaaatggt 117120
tcaaagacta gacatttacc atgggatgct aatattccca aacatacatc tataaatttg 117180
acgcttttct cttttaattc agtaaataga gagatatcag ccgcactagc atcccctttc 117240
aatagttctc cctttttaaa ggtatctaat gcggatttag aaaactctct atctcttaat 117300
gaatttttaa aatcattata tagtgttgct atctcttgcg cgtattcgcc cggatcacga 117360
ttttgtcttt caggaaagct atcgaacgta aacgtagtag ccatacgtct cagaattcta 117420
aatgatgata tacctgtttt tatttcagcg agtttagcct tttgataaat ttcttcttgc 117480
tttttcgaca tattaacgta tcgcattaat actgttttct tagcgaatga tgcagaccct 117540
tctacgtcat caaaaataga aaactcgtta ttaactatgt acgaacatag gcctcctagt 117600
ttggagacta attctttttc atcgactaga cgtttattct caaatagcga ttggtgttgt 117660
aaggatcctg gtcgtagtaa gttaaccaac atggtgaatt cttgcacact attgacgata 117720
ggtgtagccg ataaacaaat catcttatgg ttttttaacg caatggtctt agataaaaaa 117780
ttatatactg aacgagtagg acggatctta ccatcttctt tgattaatga tttagaaatg 117840
aagttatgac attcatcaat gatgacgcat attctactct tggcattaat agttttgata 117900
ttagtaaaaa atttatttct aaaattttga tcatcgtaat taataaaaat acaatccttc 117960
gttatctctg gagcgtatct gagtatagtg ttcatccaag gatcttctat caaagccttt 118020
ttcaccaata agataatagc ccaattcgta taaatatcct taagatgttt gagaatatat 118080
acagtagtca ttgttttacc gacacccgtt tcatggaaca ataaaagaga atgcatactg 118140
tctaatccta agaaaactct tgctacaaaa tgttgataat ccttgaggcg tactacgtcc 118200
gaccccatca tttcaacggg catattagta gttctgcgca atgcataatc gatataggcc 118260
gcgtgtgatt tactcattta tgagtgataa gtaataacta tgttttaaaa atcacagcag 118320
tagtttaact agtcttctct gatgtttgtt ttcgatactt tttgaatcag aagtcatact 118380
agaataaagc aacgagtgaa cgtaatagag agcttcgtat actctattcg aaaactctaa 118440
gaacttatta atgaattccg tatccactgg attgtttaaa atactaaatt gaacactgtt 118500
cacatccttc caagaagaag acttagtgac ggacttaaca tgagacataa ataaatccaa 118560
atttttttta caaacatcac tagccaccat aatggcgcta tctttcaacc agctatcgct 118620
tacgcatttt agcagtctaa catttttaaa gagactacaa tatattctca tagtatcgat 118680
tacacctcta ccgaatagag taggaagttt aataatacaa tatttttcgt ttacaaaatc 118740
aaataatggt cgaaacacgt cgaaggttaa catcttataa tcgctaatgt atagattgtt 118800
ttcagtgaga tgattattag atttaatagc atctcgttca cgtttgaaca gtttattgcg 118860
tgcgctgagg tcggcaacta cggcgtccgc tttagtactc ctcccataat actttacgct 118920
attaatcttt aaaatttcat agactttatc tagatcgctt tctggtaaca tgatatcatg 118980
tgtaaaaagt tttaacatgt cggtcggcat tctatttaga tcattaactc tagaaatctg 119040
aagaaagtaa ttagctccgt attccagact aggtaatggg cttttaccta gagacagatt 119100
aagttctggc aatgtttcat aaaatggaag aaggacatgc gttccctccc ggatattttt 119160
tacaatttca tccatttaca actctatagt ttgttttcat tattattagt tattatctcc 119220
cataatcttg gtaatactta ccccttgatc gtaagatacc ttatacaggt cattacatac 119280
aactaccaat tgtttttgta cataatagat tggatggttg acatccatgg tggaataaac 119340
tactcgaaca gatagtttat ctttccccct agatacatta gccgtaatag ttgtcggcct 119400
aaagaatatc tttggtgtaa agttaaaagt tagggttctt gttccattat tgctttttgt 119460
cagtagttca ttataaattc tcgagatggg tccgttctct gaatatagaa catcatttcc 119520
aaatctaact tctagtctag aaataatatc ggtcttattc ttaaaatcta ttcccttgat 119580
gaagggatcg ttaatgaaca aatccttggc ctttgattcg gctgatctat tatctccgtt 119640
atagacgtta cgttgactag tccaaagact tacaggaata gatgtatcga tgatgttgat 119700
actatgtgat atgtgagcaa agattgttct cttagtggca tcactatatg ttccagtaat 119760
ggcggaaaac tttttagaaa tgttatatat aaaagaattt tttcgtgttc caaacattag 119820
cagattagta tgaagataaa cactcatatt atcaggaaca ttatcaattt ttacatacac 119880
atcagcatct tgaatagaaa cgataccatc ttctggaacc tctacgatct cggcagactc 119940
cggataacca gtcggtggac catcgctaac aataactaga tcatccaaca atctactcac 120000
atatgcatct atataatctt tttcatcttg tgagtaccct ggatacgaaa taaatttatt 120060
atccgtattt ccataataag gtttagtata aacagagaga gatgttgccg catgaacttc 120120
agttacagtc gccgttggtt ggtttatttg acctattact ctcctaggtt tctctataaa 120180
cgatggttta atttgtacat tcttaaccat atatccaata aagctcaatt caggaacata 120240
aacaaattct ttgttgaacg tttcaaagtc gaacgaagag tcacgaataa cgatatcgga 120300
tactggattg aaggtcaccg ttacggtaat ttttgaatcg gatagtttaa gactgctgaa 120360
tgtatcttcc acatcaaacg gagttttaat ataaacgtat actgtagatg gttctttaat 120420
agtgtcatta ggagttaggc caatagaaat atcattaagt tcactagaat atccagagtg 120480
tttcaaagca attgtattat tgatacaatt attatataat tcttcgccct caatttccca 120540
aataacaccg ttacacgaag agatagatac gtgattaata catttatatc caacatatgg 120600
tacgtaaccg aatcttccca tacctttaac ttctggaagt tccaaactca gaaccaaatg 120660
attaagcgca gtaatatact gatccctaat ttcgaagcta gcgatagcct gattgtctgg 120720
accatcgttt gtcataactc cggatagaga aatatattgc ggcatatata aagttggaat 120780
ttgactatcg actgcgaaga cattagaccg tttaatagag tcatccccac cgatcaaaga 120840
attaatgata gtattattca ttttctattt aaaatggaaa aagcttacaa taaactccgt 120900
agagaaatat ctataatttg tgagttttcc ttaaagtaac agcttccgta aacgccgtct 120960
ttatctctta gtaagtttat tgtatttatg accttttcct tatcttcata gaatactaaa 121020
ggcaacaaag aaatttttgg ttcttctcta agagctacgt gagacttaac catagacgcc 121080
aacgaatccc tacatatttt agaacagaaa taccctactt caccaccctt gtatgtctca 121140
atactaatag gtctaaaaac caaatcttga ttacaaaacc aacacttatc aattacacta 121200
tttgtcttaa tagacacatc tgccatagat ttataatact ttggtagtat acaagcgagt 121260
gcttcttctt tagcgggctt aaagactgct ttaggtgctg aaataaccac atctggaagg 121320
cttactcgct tagccattta attacggaac tattttttta tacttctaat gagcaagtag 121380
aaaacctctc atctacaaaa acgtactcgt gtccataatc ctctaccata gtaacacgtt 121440
ttttagatct catatgtgct aaaaagtttt cccatactaa ttggttacta ttatttttcg 121500
tataattttt aacagtttga ggttttagat ttttagttac agaagtgata tcgaatattt 121560
tatccaaaaa gaatgaataa ttaattgtct tagaaggagt gttttcttgg caaaagaata 121620
ccaagtgctt aaatatttct actacttcat taatcttttc tgtactcaga ttcagtttct 121680
catcttttac ttgattgatt atttcaaaga ctaacttata atccttttta tttattctct 121740
cgttagcctt aagaaaacta gatacaaaat ttgcatctac atcatccgtg gatatttgat 121800
ttttttccat gatatccaag agttccgaga taatttctcc agaacattga tgagacaata 121860
atctccgcaa tacatttctc aaatgaataa gtttattaga cacgtggaag tttgactttt 121920
tttgtacctt tgtacatttt tgaaataccg actcgcaaaa aatacaatat tcatatcctt 121980
gttcagatac tataccgttg tgtctacaac cgctacataa tcgtagattc atgttaacac 122040
tctacgtatc tcgtcgtcca atattttata taaaaacatt ttatttctag acgttgccag 122100
aaaatcctgt aatattttta gttttttggg ctgtgaataa agtatcgccc taatatggtt 122160
accgtcctcc gccaatatag tagttaaatt atccgcacat gcagaagaac accgcttagg 122220
cggattcagt acaatgttat atttttcgta ccaactcatt taaatatcat aatctaaaat 122280
agttctgtaa tatgtctagc gctaatatat tgatcataat cctgtgcata aattaagata 122340
caacaatgtc tcgaaatcat cgacatggct tcttccatag ttagaagatc gtcgtcaaag 122400
ttagcaacgt gattcatcaa catttgctgt tttgaggcag caaatactga accgtcgcca 122460
ttcaaccatt cataaaaacc atcgtctgaa tccattgata atttcttgta ctggtttttg 122520
agagctcgca tcaatctagc atttctagct cccggattga aaacagaaag aggatcgtac 122580
atccagggtc cattttctgt aaatagaatc gtataatgtc ccttcaagaa gatatcagac 122640
gatccacaat caaagaattg gtctccgagt ttgtaacaga cagcggactt taacctatac 122700
atgataccgt ttagcataat ttctggtgat acgtcaatcg gagtatcatc tattagagat 122760
ctaaagccgg tgtaacattc tccaccaaac atattcttat tctgacgtcg ttctacataa 122820
aacatcattg ctccattaac gataacaggg gaatgaacag cactacccat cacattagtt 122880
cccaatggat caatgtgtgt aactccagaa catcttccat agcctatgtt aggaggagcg 122940
aacaccactc ttccactatt gccatcgaat gccatagaat aaatatcctt ggaattgata 123000
gaaatcggac tgtcggatgt tgtgatcatc ttcataggat taacaactat gtatggtgcc 123060
gcctgaagtt tcatatcgta actgatgccg tttataggtc tagccacaga aaccaacgta 123120
ggtctaaatc caactataga caaaatagaa gccaatatct gttcctcatc tgtcataact 123180
tgagagcatc cagtatgaat aatcttcatt agatggggat ctaccgcatc atcatcgtta 123240
caataaaaaa ttcccattct aatgttcata attgcttttc taatcatggt atgcatgttt 123300
gctctctgaa tctctgtgga aattagatct gatacacctg taatcactat cggattatcc 123360
tccgtaagac gattaaccaa caacatataa ttataagact ttacttttct aaattcataa 123420
agttgctgga ttaggctata ggtgtctcca tgtacatacg cgttctcgag cgcaggaagt 123480
ttaataccga atagtgccat cagaatagga tgaatatagt aattagtttc tggttttcta 123540
taaataaaag acaaatcttg tgaactagac atatcggtaa aatgcatgga ttggaatcgt 123600
gtagtcgaca gaagaatatg atgattagat ggagagtata ttttatctaa ctctttgagt 123660
tggtcaccga ttctaggact agctcgagaa tgaataagta ctaaaggatg agtacatttc 123720
acagaaacac tagcattgtt caatgtgctc tttacatggg taaggagttg aaatagctcg 123780
tttctatttg ttctgacaat atttagttta ttcataatgt taagcatatc ctgaatagta 123840
aagttagatg tgtcatactt gttagtagtt agatatttag caattgcatt cccatcattt 123900
ctcaatctcg tactccaatc atgcgtggat gctacttcgt cgatggaaac catacaatcc 123960
tttttggtag tctgttgagc ttgatcattt cctgcacgtt taggtttggt acgttgattt 124020
ctagcccctg cggatataaa gtcatcgtct acaatttggg acaatgaatt gcatacacta 124080
caagacaaag atttatcaga agtgtgaata tgatcttcat ctaccaaaga aagagtttga 124140
ttagtataac tagattttag tcctgcgtta gatgttaaaa aaacatcgct attgaccacg 124200
gcttccatta tttatattcg tagtttttac tcgaaagcgt gattttaata tccaatctta 124260
ttacttttgg aatcgttcaa aacctttgac taattgtaga atttgattta ttgccctacg 124320
cgtatactcc cttgcatcat atacgttcgt caccagatcg tttgtttcgg cctgaagttg 124380
gtgcatatct ctttcaacat tcgacatgag atccttaagg gccatatcgt ctagattttg 124440
ttgagatgct gctcctggat ttggattttg ttgtgctgtt gtacatactg taccaccagt 124500
aggtgtagga gtacatacag tggccacaat aggaggttga ggaggtgtaa ccgttggagt 124560
agtacaagaa atatttccat ccgattgttg tgtacatgta gttgttggta acgtctgaga 124620
aggttgggta gatggcggtg tcgtcgtctt ttgatcttta ttaaatttag agataatatc 124680
ctgaacagca ttgctcggcg tcaacgctgg aaggagtgaa ctcgccggcg catcagtatc 124740
ttcagacagc caatcaaaaa gattagacat atcagatgat gtattagttt gttgtcgtgg 124800
ttttggtgta ggagcagtac tactaggtag aagaatagga gccggtgtag ctgttggaac 124860
cggctgtgga gttatatgaa tagttggttg tagcggttgg ataggctgtc tgctggcggc 124920
catcatatta tctctagcta gttgttctcg caactgtctt tgataatacg actcttgaga 124980
ctttagtcct atttcaatcg cttcatcctt tttcgtatcc ggatcctttt cttcagaata 125040
atagattgac gactttggtg tagaggattc tgccagcctc tgtgagaact tgttaaagaa 125100
gtccatttaa ggctttaaaa ttgaattgcg attataagat taaatggcag acacagacga 125160
tattatcgac tatgaatccg atgatctcac cgaatacgag gatgatgaag aagaggaaga 125220
agatggagag tcactagaaa ctagtgatat agatcccaaa tcttcttata agattgtaga 125280
atcagcatcc actcatatag aagatgcgca ttccaatctt aaacatatag ggaatcatat 125340
atctgctctt aaacgacgct atactagacg tataagtcta tttgaaatag cgggtataat 125400
agcagaaagc tataacttgc ttcaacgagg aagattacct ctagtttcag aattttctga 125460
cgaaacgatg aagcaaaata tgctacatgt aattatacaa gagatagagg agggttcttg 125520
tcctatagtc atcgaaaaga acggagaatt gttgtcggta aacgattttg acaaagatgg 125580
tctaaaattc catctagact atattatcaa aatttggaaa cttcaaaaac gatattagaa 125640
tttatacgaa tatcgttctc taaatgtcac aatcaagtct cgcatgttca gcaatttatt 125700
gtcgtacttt atatcgtgtt cattaacgat atcttgcaaa atagtaatga ttctatcttc 125760
cttcgataga tattcttcag agattattgt cttatattct ttcttgttat ccgatatgaa 125820
tttgataaga ctttgaacat tattgatacc cgtctgttta attttttcta cagatatttt 125880
agttttggca gattctatcg tatctgtcaa tagacatcca acatcgacat tcgacgtcaa 125940
ttgtctataa atcagagtat aaattttaga aataacatta gcgaattgtt gtgcgttgat 126000
gtcgttattc tgaaacagta tgattttagg tagcattttc ttaacaaaga gaacgtattt 126060
attgttactc agttgaacag atgatatatc cagattacta acgcatctga ttccgtatac 126120
caaactttca gaagaaatgg tgtacaattg tttgtattca ttcaatgtct ctttttcaga 126180
aattagttta gagtcgaata ctgcaataat tttcaagaga tagttttcat cagataagat 126240
tttatttagt gtagatatga taaaactatt gttttgttgg agaacttgat acgccgcgtt 126300
ctctgtagtc gacgctctca aatgggaaac gatctccatt atttttttgg aatcggatac 126360
aatatcttcg gtatcttgac gcagtctagt atacatagag ttaagagaga ttagagtttg 126420
tacattaagc aacatgtctc taaatgtggc tacaaacttt tcctttttca catcatctag 126480
tttattatat accgatttca caacggcacc agatttaagg aaccagaatg aaaaactctg 126540
ataactacaa tatttcatca tagttacgat tttatcatct tctatagttg gtgtaatagc 126600
gcataccttt ttctccaaga ctggaaccaa cgtcataaaa atgtttaaat caaaatccat 126660
atcaacatct gatgcgctaa gaccagtctc gcgttcaaga ttatctttac taatggtgac 126720
gaactcatcg tatagaactc taagtttgtc cattatttat ttacagattt agttgtttaa 126780
tttatttgtg ctcttccaga gttgggatag tatttttcta acgtcggtat tatattatta 126840
ggatctacgt tcatatgtat cataatatta atcatccacg ttttgataaa tctatcttta 126900
gcttctgaaa taacgtattt aaacaaagga gaaaaatatt tagctacggc atcagacgca 126960
ataacatttt ttgtaaatgt aacgtattta gacgacagat cttcgttaaa aagttttcca 127020
tctatgtaga atccatcggt tgttaacacc attcccgcgt cagattgaat aggagtttga 127080
atagtttgtt ttggaaatag atccttcaat aacttatagt tgggtgggaa aaaatcgatt 127140
ttatcactag actctttctt ttttactatc attacctcat gaactatttc ttgaatgagt 127200
atatgtattt tctttcctat atcggacgcg ttcattggaa aatataccat gtcgttaact 127260
ataagaatat ttttatcctc gtttacaaac tgaataatat cagatgtagt tcgtaaacga 127320
actatatcat caccagcaca acatctaact atatgatatc cactagtttc ctttagtcgt 127380
ttattatctt gttccatatt agcagtcatt ccatcattta agaaggcgtc aaaaataata 127440
gggagaaatg acattttgga ttctgttaca actttaccaa aattaaggat atacggactt 127500
actatctttt tctcaacgtc aatttgatga acacacgatg aaaatgtact tcgatgagat 127560
tgatcatgta gaaaacaaca agggatacaa tatttccgca tatcatgaaa tatattaaga 127620
aatcccacct tattatattt ccccaaagga tccatgcatg taaacattat gccgttatca 127680
ttaataaaga cttctttctc atcggatctg taaaagttgt tactgatttt tttcattcca 127740
ggatctagat aattaataat gatgggtttt ctattcttat tctttgtatt ttggcatatc 127800
ctagaccagt aaacagtttc cactttggta aaatcagcag acttttgaac gctattaaac 127860
atggcattaa tggcaataac taaaaatgta aaatattttt ctatgttagg aatatggttt 127920
ttcactttaa tagatatatg gtttttggcc aaaatgatag atattttttt atccgaggat 127980
agtaaaatat tattagtcgc cgtctctata aaaatgaagc tagtctcgat atccaatttt 128040
attctagaat tgataggagt cgccaaatgt accttatacg ttatatctcc cttgatgcgt 128100
tccatttgtg tatctatatc ggacacaaga tctgtaaata gttttacgtt attaatcatc 128160
acggtatcgc cgtcgctaga taacgctaat gtaccatcca agtcccaaat ggagagattt 128220
aactgttcat cgtttagaat aaaatgatta ccggtcatat taataaagtg ttcatcgtat 128280
ctagataaca acgacttata attaatgtcc aagtcttgaa ctcgctgaat gatctttttt 128340
aacccagtta gttttagatt ggtacgaaat atattgttaa actttgattc tacagtaatg 128400
tccaaatcta gttgtggaaa tacttccatc aacattgttt caaacttgat aatattatta 128460
tctacatctt cgtacgatcc aaattccgga atagatgtat cgcacgctct ggccacccag 128520
ataaccaaaa agtcacacgc tccaggatat acattgtata aaaagctatc gttttttagt 128580
agggtttttt tctgcgtgta tacgaaggga ttaaaaatag tattatcaac gtaactatat 128640
tccaaattat tcttatgaga atagataata atatcgtcct taatatctaa caaatttcct 128700
aaatatccct ttaattgagt cattcgaagc gtcaatagaa tatgtctctt aactatttcc 128760
ggctgttgta tatttaaatg acttcgtaaa aaataatata tgggcgactt ctcatctatg 128820
taatcatatg gagtgagata tagggctcgt tctacctcct gccccttacc cacctgtaat 128880
accaattgcg gacttactat atatcgcata tttatatcgt ggggtaaagt gaaaatctac 128940
taccgatgat gtaagtctta caatgttcga accagtacca gatcttaatt tggaggcctc 129000
cgtagaacta ggggaggtaa atatagatca aacaacacct atgataaagg agaatagcgg 129060
ttttatatcc cgtagtagac gtctattcgc ccatagatct aaggatgatg agagaaaact 129120
agcactacga ttctttttac aaagacttta ttttttagat catagagaga ttcattattt 129180
gttcagatgc gttgacgctg taaaagacgt cactattacc aaaaaaaata acattatcgt 129240
ggcgccttat atagcacttt taactatcgc atcaaaagga tgcaaactta cagaaacaat 129300
gattgaagca ttctttccag aactatataa tgaacatagt aagaaattta aattcaactc 129360
tcaagtatcc atcatccaag aaaaactcgg ataccagttt ggaaactatc acgtttatga 129420
ttttgaaccg tattactcta cagtagctct ggctattcga gatgaacatt catctggcat 129480
ttttaatatc cgtcaagaga gttatctggt aagttcatta tctgaaataa catatagatt 129540
ttatctaatt aatctaaaat ctgatcttgt tcaatggagt gctagtacgg gcgctgtaat 129600
taatcaaatg gtaaatactg tattgattac agtgtatgaa aagttacaac tggtcataga 129660
aaatgattca caatttacat gttcattggc tgtggaatca aaacttccaa taaaattact 129720
taaagataga aatgaattat ttacaaaatt cattaacgag ttaaaaaaga ccagttcatt 129780
caagataagc aaacgcgata aggatacgct actaaaatat tttacttagg actggagtta 129840
gaatttatag acgactcatt tcgtttatca ttgttactat tattactatt actatcatta 129900
ttagtgttgg cattattagt attcttcttg tcatcttgtt cagaaatata cagcaatgct 129960
atacctaata ctaaatacat tatcatgctc gcaatggctc taacaacaac gaaccaaaat 130020
gaatttggtc gtagcttttg ttcacaaaaa tacataaaga aatgtctaca taaatctatg 130080
gcgccattgg ctacttgaaa tagcgccagt cctcctacag attttaatat agctgtataa 130140
catgacattt attcatcatc aaaagagaca gagtcaccat ctgtcatatt tagatttttt 130200
ttcatgtgtt caaagtatcc tctactcatt tcattataat agtttatcat acttagaatt 130260
ttaggacgga tcaatgagta agacttgact agatcgtcag tagtaatttg tgcatcgtct 130320
attctgcatc cgcttcgtcg aataatgtat agcatcgctt tgagattctc catagctatc 130380
aagtctttat acaatgacat ggaaatatct gtgaatactt tatacttctc caacatcgat 130440
gccttaacat catcgcctac tttagcattg aaaatacgtt ctattgtgta gatggatgta 130500
gcaagatttt taaacaacaa tgccatctta cacgatgatt gcctcaagtc tccaatcgtt 130560
tgtttagaac gattagctac agagtccaat gcttggctga ctagcatatt attatcttta 130620
gaaattgtat tcttcaatga ggcgtttatc atatctgtga tttcgttagt catattacag 130680
tctgactggg ttgtaatgtt atccaacata tcacctatgg atacggtaca cgtaccagca 130740
tttgtaataa tcctatctaa gatgttgtat ggcattgcgc agaaaatatc ttctcctgta 130800
atatctccac tctcgataaa tctactcaga ttattcttaa atgccttatt ctctggagaa 130860
aagatatcag tgtccatcat ttcattaata gtatacgcag aaaagatacc acgagtatca 130920
attctatcca agatacttat cggttccgag tcacagataa tggtttcctc tccttcggga 130980
gatcctgcat agaaatatct aggacaatag tttctatact gtctgtaact ctgataatct 131040
ctaaagtcac taactgatac catgaaattg agaagatcaa acgctgaagt aattaatttt 131100
tctgcctcgt ttttactaca actagttttc atcaatgtag tgacgatgta ttgtttagtt 131160
acttttggtc taatactgat gatagagata ttattgcttc ccataatgga tcttctagta 131220
gtcaccttaa agcccattga tgcgaatagc agatagataa agtcttggta tgactccttt 131280
ctaatatagt acggactacc tttgtcaccc aactttatac ccacataagc cataacaacc 131340
tctttaatag ccgtttcatg aggtttatca gccatgagcc tgagtagttg gaagaatctc 131400
atgaatcccg tctcagaaag tcctatatgc atgatagatt tatctttcct gggaaactct 131460
cgtatagtca tagatgaaat actcttcaaa gtttctgaaa taagattagt aacagtctta 131520
cctccgacta ctctaggtaa caaacaaact ctaataggtg ttttctctgc ggagataata 131580
tcagaaagga tagagcaata agtagtatta ttgtgattat aaagaccgaa tacataacag 131640
gtagaattta taaacatcat gtcctgaagg tttttagact tgtattcctc gtaatccata 131700
ccgtcccaaa acatggattt ggtaactttg atagccgtag atctttgttc cttcgccaac 131760
aggttaaaga aattaataaa gaatttgttg tttctattta tgtccacaaa ttgcacgttt 131820
ggaagcgcca cggttacatt cactgcagca ttttgaggat cgcgagtatg aagtacgatg 131880
ttattgttta ctggtatatc tggaaagaaa tctaccagtc taggaataag agattgatat 131940
cgcatagaaa tagtaaagtt tataatctca tcatcgaaga gcattttgtt accattgtaa 132000
taaatatcca ctctgtcata tgtataaatg aagtactgtt caaacatgat gagatgttta 132060
tatgttggca tagtagtgag atcgacgttt ggtaatggca atgtattaag attaactcca 132120
taatgtctag cagcatctgc gatgttataa gcgtcgtcaa agcggggtcg atcttgtatt 132180
gttatatatt gtctaacacc tataagatta tcaaaatctt gtctgcttaa tacaccgtta 132240
acaatttttg ccttgaattc ttttattggt gcattaataa catccttata gaggatgtta 132300
aacaaataag tgttatcaaa gttaagatct ggatatttct tttctgctag aacatccatt 132360
gagtcggagc catctggttt aatataacca ccgataaatc tagctctgta ttctgtatcc 132420
gtcaatctaa tattaagaag gtgttgagtg aaaggtggaa gatcgtaaaa gctgtgagta 132480
ttaatgatag gattagtttc cgaactaatg ttaattgggg tattaataat atctatattt 132540
ccagcgttaa gtgtaacatt aaacagtttt aattcacgtg acgtggtatc aattaaataa 132600
ttaatgccca atttggatat agcagcctga agctcatctt gtttagttac ggatcctaat 132660
gagttattaa gcaatatatc gaacggatga acgaaggttg ttttgagttt gtcgcatact 132720
ttgtaatcta gacatagatg cggaagaacg gtagaaacta tacgaaataa atattcagag 132780
tcctctaatt gatcaagagt aactattgac ttaataggca tcatttattt agtattaaat 132840
gacgaccgta ccagtgacgg atatacaaaa cgatttaatt acagagtttt cagaagataa 132900
ttatccatct aacaaaaatt atgaaataac tcttcgtcaa atgtctattc taactcacgt 132960
taacaacgtg gtagatagag aacataatgc cgccgtagtg tcatctccag aggaaatatc 133020
ctcacaactt aatgaagatc tatttccaga tgatgattca ccggccacta ttatcgaacg 133080
agtacaacct catactacta ttattgacga tactccacct cctacgtttc gtagagagtt 133140
attaatatcg gaacaacgtc aacaacgaga aaaaagattt aatattacag tatcgaaaaa 133200
tgctgaagca ataatggaat ctagatctat aataacttct atgccaacac aaacaccatc 133260
cttgggagta gtttatgata aagataaaag aattcagatg ttagaggatg aagtggttaa 133320
tcttagaaat caacgatcta atacaaaatc atctgataat ttagataatt ttaccaaaat 133380
actatttggt aagactccgt ataaatcaac agaagttaat aagcgtatag ccatcgttaa 133440
ttatgcaaat ttgaacgggt cccccttatc agtcgaggac ttggatgttt gttcggagga 133500
tgaaatagat agaatctata aaacgattaa acaatatcac gaaagtagaa aacgaaaaat 133560
tatcgtcact aacgtgatta ttattgtcat aaacattatc gagcaggcat tgctaaaact 133620
cggatttgaa gaaatcaaag gactgagtac cgatatcact tcagaaatta tcgatgtgga 133680
gatcggagat gactgcgatg ctgtagcatc aaaactagga atcggtaaca gtccggttct 133740
taatattgta ttgtttatac tcaagatatt cgttaaacga attaaaatta tttaatttaa 133800
tacattccca tatccagaca acaatcgtct ggattaatct gttcctgtcg tctcataccg 133860
gacgacatat taatcttttt attagtgggc atctttttag atggtttctt tttcccagca 133920
ttaactgatt cgatacctag aagatcgtga ttgatctctc cgaccattcc acgaacttct 133980
aattggccgt ctctgacggt accataaact attttaccag cattagtaac agcttggaca 134040
atctgaccat ccatcgcatt gtacgatgta gtagtaactg ttgttctacg tctaggagca 134100
ccagaagtat ttttggagcc cttggaggct gatgtagaag aagacgagga ttttgatttt 134160
ggtttacatg taatacattt tgaactcttt gattttgtat cacatgcgcc ggcagtcaca 134220
tctgtttgag aattaagatt attgttgcct cctttgacgg ctgcatctcc accgatttgc 134280
gctagtagat ttttaagctg tggtgtaatc ttattaactg tttcgatata atcatcgtaa 134340
ctgcttctaa cggctaaatt ttttttatcc gccatttaga agctaaaaat atttttattt 134400
atgcagaaga tttaactaga ttatacaatg aactaatatg atccttttcc agattattta 134460
caaacttggt attttttggt tctggaggag gcgaatttaa attcggactt ggattcggat 134520
tttgtaagtt cttgatctta ttatacatcg agtataggat ggcgacagta actgctacac 134580
aaataccgat caaaagaaga ataccaatca tttattgaca ataacttcac tattgatcaa 134640
gtatgcaata tatcatcttt tcactaaata agtagtaata atgattcaac aatgtcgaga 134700
tatatggacg ataataattt agttcatgga aatatcgcta tgattggtgt gaatgactcc 134760
gctaactctg tggggtgcgc agtgctttcc ccacatagaa taaattagca ttccgactgt 134820
gataataata ccaagtataa acgccataat actcaatact ttccatgtac gagtgggact 134880
agtagactta ctaaagtcaa taaaggcgaa gatacacgaa agaatcaaaa gaatgattcc 134940
agcgattagc acgccggaaa aataatttcc aatcataagc atcatgtcca tttaactaat 135000
aaaaatttta aatcgccgaa tgaacaaagt ggaatataaa ccatataaaa acaatagttt 135060
gtactgcaaa aataatatct atttttgttt tcgaagatat ggtaaaatta aatagtagta 135120
cacagcatgt tataactaac agcagcaacg gctcgtaatt acttatcatt tactagacga 135180
aaaggtggtg ggatattttc ttgctcaaat aatacgaata tatcacccat ccattttatg 135240
cgatgtttat atactctaat ctttaataga tctatagacg acgggtttac caacaatata 135300
gattttatcg attcatctaa tttaaaccct tccttaaacg tgaatgatct attatctggc 135360
ataacgatga ccctacctga tgaatcggac aatgtactgg gccatgtaga ataaattatc 135420
aacgaattat cgtctacgaa catttatatc atttgtttta attttaggac gcgaataaat 135480
ggatataaaa tagaaaataa cagatattac aaccagtgtt atggccgcgc ccaaccaggt 135540
aggcagtttt attttatctt ttactacagg ttctcctgga tgtacgtcac caacggcgga 135600
cgtagttcta gtacaattag acgtaagttc cgcttgggaa ttttttaacg ctaaagagtt 135660
aacgttaatc gtgcacccaa cgtatttaca tctagttctt tgaacatctt gattataata 135720
taaccatttt ctatctctag attcgtcagt gcactcatgt aaccaacata ccctaggtcc 135780
taaatattta tctccggaat tagattttgg ataattcgcg caccaacaat ttctatttcc 135840
tttatgatcg ttacaaaaga cgtataatgc cgtatcccca aaagtaaaat aatcaggacg 135900
aataattcta ataaactcag aacaatatct cgcatccata tgtttggagc aaatatcgga 135960
ataagtagac atagccggtt tccgttttgc acgtaaccat tctaaacaat tggggtttcc 136020
aggatcgttt ctacaaaatc cagtcatgaa atcatcacaa tgttctgtct tgtaattatt 136080
attaaatatt tttggacagt gtttggtatt tgtcttagaa caacattttg ccacgctatc 136140
actatcgccc aggagataat ccttttttat aaaatgacat cgttgcccgg atgctatata 136200
atcagtggcg tgttttaaat ccttaatata ttcaggagtt acctcgttct gataatagat 136260
taatgatcca ggacgaaatt tgaaagaact acatggttct ccatgaatta atacatattg 136320
tttagcaaat tcaggaacta taaaactact acaatgatct atcgacatac catctatcaa 136380
acaaaacttg ggtttaattt ctcccggaga tgtttcataa tagtacgtat aactttcttc 136440
tgcaaactta acagctctat tatattcagg ataattaaaa cctaattcca tatatttgtc 136500
tcgtatatct gctattcctg gtgctatttt gattctatta agagtaacag ctgcccccat 136560
tcttaataat cgtcagtatt taaactgtta aatgttggta tatcaacatc taccttattt 136620
cccgcagtat aaggtttgtt gcaggtatac tgttcaggaa tggttacatt tatacttctt 136680
ctatagtcct gtctttcgat gttcatcaca tatgcaaaga acagaataaa caaaataatg 136740
taagaaataa tattaaatat ctgtgaattc gtaaatacat tgattgccat aataattaca 136800
gcagctacaa tacacacaat agacattccc acagtgttgc cattacctcc acgatacatt 136860
tgagttacta agcaataggt aataactaag ctagtaagag gcaatagaaa agatgagata 136920
aatatcatca atatagagat tagaggaggg ctatatagag ccaagacgaa caaaatcaaa 136980
ccgagtaacg ttctaacatc attatttttg aagattccca aataatcatt cattcctcca 137040
taatcgtttt gcatcatacc tccatcttta ggcataaacg attgctgctg ttcctctgta 137100
aataaatctt tatcaagcac tccagcaccc gcagagaagt cgtcaagcat attgtaatat 137160
cttaaataac tcatttatat attaaaaaat gtcactatta aagatggagt ataatcttta 137220
tgccgaacta aaaaaaatga cttgtggtca acccctaagt ctttttaacg aagacgggga 137280
tttcgtagaa gttgaaccgg gatcatcctt taagtttctg atacctaagg gattttacgc 137340
ctctccttcc gtaaagacga gtctagtatt cgagacatta acaacgaccg ataataaaat 137400
cactagtatc aatccaacaa atgcgccaaa gttatatcct cttcaacgca aagtcgtatc 137460
tgaagtagtt tctaatatga ggaaaatgat cgaatcaaaa cgtcctctat acattactct 137520
tcacttggcg tgtggatttg gtaagactat taccacgtgt tatcttatgg ctacacacgg 137580
tagaaaaacc gtcatttgcg tacccaataa aatgttaata catcaatgga agacacaggt 137640
agaggcagtc ggattggaac ataagatatc catagatgga gtaagtagtc tattaaagga 137700
actaaagact caaagtccgg atgtattaat agtagtcagt agacatctga caaacgatgc 137760
cttttgtaaa tatatcaata agcattatga tttgttcatc ttggatgaat cacatacgta 137820
taatctgatg aacaatacag cagttacaag atttttagcg tattatcctc cgatgatgtg 137880
ttatttttta actgctacac ctagaccagc taacagaatt tattgtaaca gtattattaa 137940
tattgccaag ttatccgatc taaaaaaaac tatctatgcg gtagatagtt tttttgagcc 138000
atattccaca gacaatatta gacatatgat aaaacgatta gatggaccat ctaataaata 138060
tcatatatat actgagaagt tattatctgt agacgagcct agaaatcaac ttattcttga 138120
taccctggta gaagaattca agtcaggaac tattaatcgc attttagtta ttactaaact 138180
acgtgaacat atggtattat tctacaaacg attattagat cttttcggac cagaggttgt 138240
atttatagga gacgcccaaa atagacgtac tccagatatg gtcaaatcaa tcaaggaact 138300
aaatagattt atattcgtat ccaccttatt ttattccggt actggtttag atattcctag 138360
tttggattcg ttgttcattt gctcggcagt aatcaacaat atgcaaatag agcaattact 138420
agggagggta tgtcgagaaa cagaactatt agataggacg gtatatgtat ttcctaacac 138480
atccatcaaa gaaataaagt acatgatagg aaatttcatg caacgaatta ttagtctgtc 138540
tgtagataaa ctaggattta aacaaaaaag ttatcggaaa catcaagaat ccgatcccac 138600
ttttgtatgt acaacatcct ccagagaaga acgtgtatta aatagaatat ttaactcgca 138660
aaatcgttaa gaagtttaag cgacgatccg catgctgcac aggccagtgt attacccctc 138720
atagtattaa tataatccaa tgatactttt gtgatgtcgg aaatcttaac caatttagac 138780
tgacaggcag aacacgtcat gcaatcatca tcgtcatcga taactgtagt cttgggcttc 138840
tttttgcggc tcttcattcc ggaacgcaca ttggtgctat ccatttaggt agtaaaaaat 138900
aagtcagaat atgccctata acacgatcgt gcaaaacctg gtatatcgtc tctatcttta 138960
tcacaatata gtgtatcaac atctttatta ttattgacct cgtttatctt ggaacatgga 139020
atgggaacat ttttgttatc aacggccacc tttgccttaa ttccagatgt tgtaaaatta 139080
taactaaaca gtctatcatc gacacaaatg aaattcttgt ttagacgttt gtagtttacg 139140
tatgcggctc gttcgcgtct cattttttca gatattgcag gtactataat attaaaaata 139200
agaatgaaat aacataggat taaaaataaa gttatcatga cttctagcgc tgatttaact 139260
aacttaaaag aattacttag tctgtacaaa agtttgagat tttcagattc tgcggctata 139320
gaaaagtata attctttggt agaatgggga acatctactt actggaaaat aggcgtgcaa 139380
aaggtagcta atgtcgagac gtcaatatct gattattatg atgaggtaaa aaataaaccg 139440
tttaatattg atccgggcta ttacattttc ttaccggtat attttgggag cgtctttatt 139500
tattcgaagg gtaaaaatat ggtagaactt ggatctggaa actcttttca aataccagat 139560
gatatgcgaa gtgcgtgtaa caaagtatta gacagcgata acggaataga ctttctgaga 139620
tttgttttgt taaacaatag atggataatg gaagatgcta tatcaaaata tcagtctcca 139680
gttaatatat ttaaactagc tagtgagtac ggattaaaca tacccaaata tttagaaatt 139740
gaaatagagg aagacacatt atttgacgac gagttatact ctattataga acgctctttc 139800
gatgataaat ttccaaaaat atccatatcg tatattaagt tgggagaact tagacggcaa 139860
gttgtagact ttttcaaatt ctcattcatg tatattgagt ccatcaaggt agatcgtata 139920
ggagataata tttttattcc tagcgttata acaaaatcag gaaaaaagat attagtaaaa 139980
gatgtagacc atttaatacg atctaaggtt agagaacata catttgtaaa agtaaaaaag 140040
aaaaacacat tttccatttt atacgactat gatggaaacg gaacagaaac tagaggagaa 140100
gtaataaaac gaattataga cactatagga cgagactatt atgttaacgg aaagtatttc 140160
tctaaggttg gtagtgcagg cttaaagcaa ttgactaata aattagatat taatgagtgc 140220
gcaactgtcg atgagttagt tgatgagatt aataaatccg gaactgtaaa acgaaaaata 140280
aaaaaccaat cagcatttga tttaagcaga gaatgtttgg gatatccaga agcggatttt 140340
ataacgttag ttaataacat gcggttcaaa atagaaaatt gtaaggttgt aaatttcaat 140400
attgaaaata ctaattgttt aaataacccg agtattgaaa ctatatatgg aaactttaac 140460
cagttcgtct caatctttaa tgtcgtcacc gatgtcaaaa aaagattatt cgagtgaaat 140520
aatatgcgcc tttgatatag gtgcaaaaaa tcctgccaga actgttttag aagtcaagga 140580
taactccgtt agggtattgg atatatcaaa attagactgg agttctgatt gggaaaggcg 140640
catagctaaa gatttgtcac aatatgaata cactacagtt cttctagaac gtcagcctag 140700
aaggtcgccg tatgttaaat ttatctattt tattaaaggc tttttatatc atacatcggc 140760
tgccaaagtt atttgcgtct cgcctgtcat gtctggtaat tcatatagag atcgaaaaaa 140820
gagatcggtc gaagcatttc ttgattggat ggacacattc ggattgcgag actccgttcc 140880
ggatagacgc aaattagacg atgtagcgga tagtttcaat ttggctatga gatacgtatt 140940
agataaatgg aatactaatt atacacctta taataggtgt aaatctagaa attacataaa 141000
aaaaatgtaa taacgttagt aacgccatta tggataatct atttaccttt ctacatgaaa 141060
tagaagatag atatgccaga actattttta actttcatct aataagttgc gatgaaatag 141120
gagatatata tggtcttatg aaagaacgca tttcctcaga ggatatgttt gataatatag 141180
tgtataataa agatatacat cctgccatta agaaactagt gtattgcgac atccaactta 141240
ctaaacacat tattaatcag aatacgtatc cggtatttaa cgattcttca caagtgaaat 141300
gttgtcatta tttcgacata aactcagata atagcaatat tagctctcgt acagtagaga 141360
tatttgagag ggaaaagtca tctcttgtat catatattaa aactaccaat aagaagagaa 141420
aggtcaatta cggcgaaata aagaaaactg ttcatggagg cactaatgca aattactttt 141480
ccggtaaaaa gtctgacgag tatctgagta ctacagttag atccaacatt aatcaacctt 141540
ggatcaaaac catttctaag agaatgagag tagatatcat taatcactct atagtaacgc 141600
gtggaaaaag ctctatatta caaactatag aaattatttt tactaataga acatgtgtga 141660
aaatattcaa ggattctact atgcacatta ttctatccaa ggacaaggat gaaaaggggt 141720
gtatacacat gattgacaaa ttattctatg tctattataa tttatttctg ttgttcgaag 141780
atatcatcca aaacgagtac tttaaagaag tagctaatgt tgtaaaccac gtactcacgg 141840
ctacggcatt agatgagaaa ttattcctaa ttaagaaaat ggctgaacac gatgtttatg 141900
gagttagcaa tttcaaaata gggatgttta acctgacatt tattaagtcg ttggatcata 141960
ccgttttccc ctctctgtta gatgaggata gcaaaataaa gttttttaag gggaaaaagc 142020
tcaatattgt agcattacga tctctggagg attgtataaa ttacgtgact aaatccgaga 142080
atatgataga aatgatgaag gaaagatcga ctattttaaa tagcatagat atagaaacgg 142140
aatcggtaga tcgtctaaaa gaattgcttc taaaatgaaa aaaaacactg attcagaaat 142200
ggatcaacga ctcggatata agtttttggt gcctgatcct aaagccggag ttttttatag 142260
accgttacat ttccaatatg tatcgtattc taattttata ttgcatcgat tgcatgaaat 142320
cttgaccgtc aagcggccac tcttatcgtt taagaataat acagaacgaa ttatgataga 142380
aattagcaat gttaaagtga ctcctccaga ttactcacct ataatcgcga gtattaaagg 142440
taagagttat gacgcattag ccacgttcac tgtaaatatc tttaaagagg taatgaccaa 142500
agagggtata tccatcacta aaataagtag ttatgaggga aaagattctc atttgataaa 142560
aattccgcta ctaataggat acgggaataa aaatccactt gatacagcca agtatcttgt 142620
tcctaatgtc ataggtggag tctttatcaa taaacaatct gtcgaaaaag taggaattaa 142680
tctagtagaa aagattacaa catggccaaa atttagggtt gttaagccaa actcattcac 142740
tttctcgttt tcctccgtat cccctcctaa tgtattaccg acaagatatc gccattacaa 142800
gatatctctg gatatatcac aattggaagc gttgaatata tcatcgacaa agacatttat 142860
aacggtcaat attgttttgc tgtctcaata tttatctaga gtgagtctag aattcattag 142920
acgtagttta tcatacgata tgcctccaga agttgtctat ctagtaaacg cgataataga 142980
tagtgctaaa cgaattactg aatctattac tgactttaat attgatacat acattaatga 143040
cctggtggaa gctgaacaca ttaaacaaaa atctcagtta acgatcaacg agttcaaata 143100
tgaaatgctg cataactttt tacctcatat gaactataca cccgatcaac taaagggatt 143160
ttatatgata tctttactaa gaaagtttct ctactgtatc ttccacactt ctagatatcc 143220
agatagagat tcgatggttt gtcatcgcat cctaacgtac ggcaaatatt ttgagacgtt 143280
ggcacatgat gaattagaga attacatagg caacatccga aacgatatca tgaacaatca 143340
caagaacaga ggcacttacg cggtaaacat tcatgtacta acaactcccg gacttaatca 143400
tgcattttct agtctattga gtggaaagtt caaaaagtca gacggtagtt atcgaacaca 143460
tcctcactat tcatggatgc agaatatttc tattcctagg agtgttggat tttatccgga 143520
tcaagtaaag atttcaaaga tgttttctgt cagaaaatac catccaagtc aatatcttta 143580
cttttgttca tcagacgttc cggaaagagg tcctcaggta ggtttagtat ctcaattgtc 143640
tgtcttgagt tccattacaa atatactaac gtctgagtat ttggatttgg aaaagaaaat 143700
ttgtgagtat atcagatcat attataaaga tgatataagt tactttgaaa caggatttcc 143760
aatcactata gaaaatgctc tagtcgcatc tcttaatcca aatatgatat gtgattttgt 143820
aactgacttt agacgtagaa aacggatggg attcttcggt aacttggagg taggtattac 143880
tttagttagg gatcacatga atgaaattcg cattaatatt ggagcgggaa gattagtcag 143940
accattcttg gttgtggata acggagagct catgatggat gtgtgtccgg agttagaaag 144000
cagattagac gacatgacat tctctgacat tcagaaagag tttccgcatg tcatcgaaat 144060
ggtagatata gaacaattta cttttagtaa cgtatgtgaa tcggttcaaa aatttagaat 144120
gatgtcaaag gatgaaagaa agcaatacga tttatgtgac tttcctgccg aatttagaga 144180
tggatatgtg gcatcttcat tagtgggaat caatcacaat tctggaccca gagctattct 144240
tggatgtgct caagctaaac aagctatctc ttgtctgagt tcggatatac gaaataaaat 144300
agacaatgga attcatttga tgtatccaga gaggccaatc gtgattagta aggctttaga 144360
aacttcaaag attgcggcta attgcttcgg ccaacatgtt actatagcat taatgtcgta 144420
caaaggtatc aatcaagagg atggaattat cattaaaaaa caatttattc agagaggcgg 144480
tctcgatatt gttacagcca agaaacatca agtagaaatt ccgttggaaa actttaataa 144540
caaagaaaga gataggtcta acgcctattc aaaattagaa agtaatggat tagttagact 144600
gaatgctttc ttggaatccg gagacgctat ggcacgaaat atctcatcaa gaactcttga 144660
agatgatttt gctagagata atcagattag cttcgatgtt tccgagaaat ataccgatat 144720
gtacaaatct cgcgttgaac gagtacaagt agaacttact gacaaagtta aggtacgagt 144780
attaaccatg aaagaaagaa gacccattct aggagacaaa tttaccacta gaacgagtca 144840
aaagggaaca gtcgcgtatg tcgcggatga aacggaactt ccatacgacg aaaatggtat 144900
cacaccagat gtcattatta attctacatc catcttctct agaaaaacta tatctatgtt 144960
gatagaagtt attttaacag ccgcatattc tgctaagccg tacaacaata agggagaaaa 145020
ccgacctgtc tgttttccta gtagtaacga aacatccatc gatacatata tgcaattcgc 145080
taaacaatgt tatgagcatt caaatccgaa attgtccgat gaagaattat cggataaaat 145140
cttttgtgaa aagattctct atgatcctga aacggataag ccttatgcat ccaaagtatt 145200
ttttggacca atttattact tgcgtctgag gcatttaact caggacaagg caaccgttag 145260
atgtagaggt aaaaagacga agctcattag acaggcgaat gagggacgaa aacgtggagg 145320
aggtatcaag ttcggagaaa tggagagaga ctgtttaata gcgcatggtg cagccaatac 145380
tattacagaa gttttgaaag attcggaaga agattatcaa gatgtgtatg tttgtgaaaa 145440
ttgtggagac atagcagcac aaatcaaggg tattaataca tgtcttagat gttcaaaact 145500
taatctctct cctctcttaa caaaaattga taccacacac gtatctaaag tatttcttac 145560
tcaaatgaac gccagaggcg taaaagtcaa attagatttc gaacgaagac ctccttcgtt 145620
ttataaacca ttagataaag ttgatctcaa gccgtctttt ctggtgtaat attctagttt 145680
ggtagtagat acatatcaat atcatcaaat tcgagatccg aattataaaa tgggcgtgga 145740
ttgttaacta tagaatcgga cgtctgatat tcgaaaatct gtggagtttc aggttttggt 145800
ggaggtgtaa ctgctacttg ggatactgaa gtctgatatt cagaaagctg tggatgttct 145860
ggttcggcat ccaccgatgg tgttacacca ctactaattg gttcagtaac gtctgtggac 145920
gatggaggca ccacttctac agaacctgta gcctcagtca tcaacggagc tacttcaatg 145980
cgaggaaatg tataatttgg taatggtttc tcatgtggat ctgaagaaga ggtaagatat 146040
ctactagaaa gataccgatc acgttctagt tctcttttgt agaacttaac tttttctttc 146100
tccgcatcta gttgatattc caacctcttc acgttactac gttcagattc caattcacgt 146160
tcgcatgggt tacctccaca gtttttacga gcgatttcac gttcagcctt catgcgtctc 146220
tccctctctc tatcgagttt atcagagcag tctttctgaa ggcgatcgaa ctccataaat 146280
ttctccaacg ctttgattgt ttccatagat ttccgaagtt cagcttttag gactgtgatt 146340
ctttttcttt cgaattcaca gctggatgta caaccgtttc cattaccgcc atctctaagt 146400
ttcttttcta gatcggcaac atttcatccc catgcctttt acattcctcg agtctactgt 146460
cgtcgaaata tcgttccagc tccttttcga catcaataac tttagcacgt tgtctctcaa 146520
gctctctttt gtagttatct gattccctgg cacgtttaag atcttcatgc aattgagtca 146580
gctcttaact tcctctcttg cttcttcgtc atagtactta caatcactat gggatccatt 146640
gttaccacgt ctacactcgg cgagctcgcg tttaagagat tcaatttccc gtttgtattg 146700
gtccatgttt ccattgctac caccattaga tttacaggct gctagttgtc gttcgagatc 146760
agaaatacgg gttttcttgg aattgatttc gtcgatgtac ttggcatcga aacacttatt 146820
aagttctttt tccaattcta cgattttatt tctttcgcga gtcaattccc tcctgtagta 146880
actatctgtt ttgtcagatt cacgctctct acgtagactt tcttgcaagt tactaatttg 146940
ttccctagca cgtccgagtt tagttttata tgctgaatag agttctgatt catcctttga 147000
gcagatctct agcgatcgtt taagattcct gattctagtc tttagcctat ttacctcctc 147060
agaagatgtt ccgttaccgt tgcgtttaca ctcgttaagc tgtctatcaa gatccatgat 147120
tctatctcta aaacgttgca tctctctttc catatcagca ttgctttcat tattacgtct 147180
gcagtcactc aactgtcttt caatatctga gattctatct ctaagacgtc gcatctctct 147240
ctgtttcggc attggtttca ttattacgtc tacagtcgtt caactgtctt tcaagatctg 147300
atattctaga ttggagtctg ctaatctctg tagcattttc acggcattca ctcagttgtc 147360
tttcaagatc tgaaatttta gattggagtc tgctaatctc tgtaagattt cctcctccgc 147420
tctcgatgca gtcggtcaac ttattctcta gttctctaat acgcgaacgc agtgcatcaa 147480
cttcttgcgt gtcttcctgg ttgcgtgtac attcatcgag tctagattcg agatctctaa 147540
cgcgtcgtcg ttcttcctca agttctctgc gtactacaga aagcgtgtcc ttatcttgtt 147600
gatatttagc aatttctgat tctagagtac tgattttgct tacgtagtta ctaatagttg 147660
tcttggcctt atcaagatcc tccttgtatt tgtcgcattc cttgatatcc ctacgaagtc 147720
tggacagttc ccattcgaca ttacgacgtt tatcgatttc agctcggaga tcgtcatcgc 147780
gttgttttag ccacatacga ctgagttcaa gttctcgttg acaagatcca tctacttttc 147840
cattcctaat agtatccagt tccttttcta gttctgaacg catttcttgt tccctatcaa 147900
gcgattctct caattctcgg atagtcttct tatcaatttc taataaatct gaaccatcat 147960
ctgtcccatt ttgaatatcc ctgtgttctt tgatctcttt tgtaagtcgg tcgattcttt 148020
cggttttata aacagaatcc ctttccaaag tcctaatctt actgagttta tcactaagtt 148080
ctgcattcaa ttcggtgagt tttctcttgg cttcttccaa ctctgtttta aactctccac 148140
tattttcgca ttcttcctcg catttatcta accattcaat tagtttatta ataactagtt 148200
ggtaatcagc gattcctata gccgttcttg taattgtggg aacataatta ggatcttcta 148260
atggattgta tggcttgata gcatcatctt tatcattatt agggggatgg acaaccttaa 148320
ttggttggtc ctcatctcct ccagtagcgt gtggttcttc aataccagtg ttagtaatag 148380
gcttaggcaa atgcttgtcg tacgcgggca cttcctcatc catcaagtat ttataatcgg 148440
gttctacttc agaatattct tttctaagag acgcgacttc gggagttagt agaagaactc 148500
tgtttctgta tctatcaacg ctggaatcaa tactcaagtt aaggatagcg aatacctcat 148560
cgtcatcatc cgtatcctct gaaacgccat catatgacat ttcatgaagt ctaacgtatt 148620
gataaataga atcagattta gtattaaaca gatccttaac ctttttagta aacgcatatg 148680
tatattttag atctccagat ttcataatat gatcacatgc cttaaatgtc agtgcttcca 148740
tgatataatc tggaacacta atgggtgacg aaaaagatac agcaccatat gctacgttga 148800
taaataaatc tgaaccacta agtagataat gattaatgtt aaggaaaaga aaatattcag 148860
tgtataggta tgtcttggcg tcatatcttg tactaaacac gctaaacagt ttgttaatgt 148920
gatcaatttc caatagatta attagagcag cgggaatacc aacaaacata ttaccacatc 148980
cgtattttct atgaatatca catatcatgt taaaaaatct tgatagaaga gcgaatatct 149040
cgtctgactt aatgagtcgt agttcagcag caacataagt cataactgta aatagaacat 149100
actttcctgt agtgttgatt ctagactcca catcaacacc attattaaaa atagttttat 149160
atacatcttt aatctgctct ccgttaatcg tcgaacgttc tagtatacgg aaacactttg 149220
atttcttatc tgtagttaat gacttagtga tatcacgaag aatattacga attacatttc 149280
ttgtttttct tgagagacct gattcagaac tcaactcatc gttccatagt ttttctacct 149340
cagtggcgaa atctttggag tgcttggtac atttttcaat aaggttcgtg acctccattt 149400
attataaaaa atttattcaa aacttaacta caatcgggta attataagat cgtagatctc 149460
ccatgtggcg gaatactacc atctatcgca tgtggatgga cagtaggtaa tggccatggg 149520
aacagtaatg attgcatatt tatctttctt gctagtatta ctgcatattg tcccaatgtt 149580
tcgatgtgat gttctaacct atcaactgcc gctgtatcac aacaatagtg tccgatgaaa 149640
ttaagattat gatccaatgt gtttaatata tgattatcaa gtcttatacg atccgcgtct 149700
tttttgacag gatcaggttc ttctacagga agaagtttcg gcctcttatg atattcatgt 149760
ctgggaaacg gtggtctagg gtgaggctcc ggtatcggag tgggttttgg attataatca 149820
tcatcgtcta tgacatcatc atcatcttcg acttcgatat ttattttgct atcttgatga 149880
tgtcctgtat cagttgcatt ttcagcactc gactgaatat tagcgcattc attgtctatt 149940
attaccatat ttctaaaccc aaaatgtatg tgttgaacat cagtactatc gttgatgagt 150000
cttatagcat gaattcgctt atcgttatcg ggtttatctt ctgtcacctt agcaattcct 150060
tttttattaa actctacata atcatatcca tttctattgt ttgttctaat ataaacgagt 150120
atagcatcat tgctaaattt ttcaatagta tcgaaaacag aatatcctaa accatataat 150180
atatattcag gaacactcaa actaaatgtc caggattctc ctaaatacgt aaactttaat 150240
agtgcgaaat cattcaaaaa tctaccactt atagatagat agtacataaa tgcgtatagt 150300
agtctaccta tctctttatt atgaaaaccg gcattacgat catatatgtc gtgatatacc 150360
tgtgatccgt ttacgttaaa ccataaatac atgggtgatc ctataaacat gaatttattt 150420
ctaattctca gagctatagt taattgaccg tgtaatattt gcttacatgc atacttgata 150480
cgcttattaa taagattttt atcattgctc gttatctcag aatcgtatat ataaggagta 150540
ccattgtgat tcttaccaga tattatacaa aatactatat ataaaatata ttgacccacg 150600
ttagtaatca tataaatgtt taacgtttta aattttgtat ttaatgatcc attatcatac 150660
gctagcatgg tcttatgata ttcattcttt aaaatataat attgtgttag ccattgcatt 150720
ggggctccta atggagattt tttattctca tccattttag gataggcttt cataaagtcc 150780
ctaataactt cgtgaataat gtttctatgt tttctactga tgcatgtatt tgcttcgatt 150840
tttttatccc atgtttcatc tatcatagat ttaaacgcag taatgctcgc aacattaaca 150900
tcttgaaccg ttggtacaat tccgttccat aaatttataa tgttcgccat ttatataact 150960
cattttttga atatactttt aattaacaaa agagttaagt tactcatatg gacgccgtcc 151020
agtctgaaca tcaatctttt tagccagaga tatcatagcc gctcttagag tttcagcgtg 151080
attttccaac ctaaatagaa cttcatcgtt gcgtttacaa cacttttcta tttgttcaaa 151140
ctttgttgtt acattagtaa tctttttttc caaattagtt agccgttgtt tgagagtttc 151200
ctcattgtcg tctccatcgg ctttaacaat tgcttcgcgt ttagcctctg gctttttagc 151260
agcctttgta gaaaaaaatt cagttgctgg aattgcaaga tcgtcatctc cggggaaaag 151320
agttccgtcc atttaaagta cagattttag aaactgacac tctgcgttat ttatatttgg 151380
tacaacacat ggattataaa tatcgatgtt aataacatca gaaaatgtaa agtctataca 151440
ttgttgcatc gtgttaaatt ttctaatgga tctagtatta ttgggtccaa cttctgcctg 151500
aaatccaaat atggaagcgg atacaaaacc gtttcctgga taaaccacac atctccactt 151560
ttgctttaca tcagaaattg tgtcgttgac atcttgaact ctcctatcta atgccggtgt 151620
tccacctata gattttgaat attcgaatgc tgcatgagta gcattaaatt ccttaatatt 151680
gccataattt tcatatattg agtaaccctg gataaaaagt aaacacaccg cagccgtcgc 151740
taccacaata aaaaaaattg atagagagtt catttataat ctattagaag ctgacaaaat 151800
ttttttacac gcatcagaca atgctttaat aaatagttca acatctactt ttgtcatatc 151860
gaaccgatgg tatgattcta acctagaatt acatccgaaa aagttgacta tgttcatagt 151920
cattaagtca ttaacaaaca acattccaga ctctggatta taagacgata ctgtttcgtc 151980
acaattacct accttaatca tgtgattatg aatattggct attagagcac cttctaagaa 152040
atctataata tctttgaaac acgatttaaa atcaaaccac gaatatactt ctacgaagaa 152100
agttagttta cccataggag aaataactat aaatggagat ctaaatacaa aatccggatc 152160
tatgatagtt ttaacattat tatattctct attaaatacc tccacatcta aaaatgttaa 152220
ttttgaaact atgtcttcgt ttattaccgt acctgaacta aacgctataa gctctattgt 152280
ttgagaactc tttaaacgat attcttgaaa tacatgtaac aaagtttcct ttaactcggt 152340
cggtttatct accatagtta cagaatttgt atccttatct ataatataat aatcaaaatc 152400
gtataaagtt atataattat cgcgttcaga ttgggatctt ttcaaataga ctaaaaaccc 152460
catttctcta gtaagtatct tatgtatatg tttgtaaaat atcttcatgg tgggaatatg 152520
ctctaccgca gttagccatt cctcattgac agcggtagat gtattagaca aaactattcc 152580
aatgtttaac aagggccatt ttacgagatt attaaatcct tgtttgataa atgtagccaa 152640
tgagggttcg agttcaacga cgattgaatt ctcttcccgc ggatgctgca tgatgaacga 152700
cgggatgttg ttcgattgat ttggaattct ttttcgactt tttgtttata ttaaatattt 152760
taaaatttat agcggatagc aattcatgta ccacggataa tgtagacgcg tattgcgcat 152820
cgatatcttt attattagat aaatttatca ataaatgtga gaagtttgcc tcgttaaggt 152880
cttccattta aatattatat aaacatttgt gtttgtaact tattcgtctt ttatggaata 152940
gttttttact agtaaagctg caattacaca ctttgtccgt aaaacataaa tataaacacc 153000
agcttttatc aatcgttcca aaaagtcgac ggcggacatt tttaacatgg catctatttt 153060
aaatacactt aggtttttgg aaaaaacatc attttataat tgtaacgatt caataactaa 153120
agaaaagatt aagattaaac ataagggaat gtcatttgta ttttataagc caaagcattc 153180
taccgttgtt aaatacttgt ctggaggagg tatatatcat gatgatttgg ttgtattggg 153240
gaaggtaaca attaatgatc taaagatgat gctattttac atggatttat catatcatgg 153300
agtgacaagt agtggagcaa tttacaaatt gggatcgtct atcgatagac tttctctaaa 153360
taggactatt gttacaaaag ttaataataa ttataattat gatgatacat tttttgacga 153420
cgatgattga tcgctattgc acaattttgt ttttttactt tctaatatag cgtttagatt 153480
ctttttcatg tgcgaatatt gatttactaa aatatctatg tttaactttt gttctataac 153540
gtccttatcg gcggtatcgg tacatatacg taattcacct tcacaaaata cggagtcttc 153600
gataataata gccaatcgat tattggatct agctgtctgt atcatattca acatgtttaa 153660
tatatccttt cgtttcccct ttacaggcat cgatcgtagc atattttccg cgtctgatat 153720
ggaaatgtta aaactacaaa aatgcgtaat gttagcccgt cctaatattg gtacgtgtct 153780
ataagtttgg catagtagaa taatagacgt gtttaaatgc cttccgaagt ttaagaattc 153840
tattagagta ttgcattttg atagtttatc acctacatca tcaaaaataa gtaaaaagtg 153900
tgctgatttt ttatgatttt gtgcgacagc aatacatttt tctatgttac ttttagttcg 153960
tatcagatta tattctagag attcctgact actaacgaaa ttaatatgat ttggccaaat 154020
gtatccatca taatctgggt tataaacggg tgtaaacaag aatatatgtt tatatttttt 154080
aactagtgta gaaaacagag atagtaaata gatagttttt ccagatccag atcctcccgt 154140
taaaaccatt ctaaacggca tttttaataa attttctctt gaaaattgtt tttcttggaa 154200
acaattcata attatattta cagttactaa attaatttga taataaatca aaatatggaa 154260
aactaaggtt gttagtaggg aggagaacaa agaaggcaca tcgtgatata aataacattt 154320
attatcatga tgacaccaga aaacgacgaa gagcagacat ctgtgttctc cgctactgtt 154380
tacggagaca aaattcaggg aaagaataaa cgcaaacgcg tgattggtct atgtattaga 154440
atatctatgg ttatttcact actatctatg attaccatgt ccgcgtttct catagtgcgc 154500
ctaaatcaat gcatgtctgc taacgaggct gctattactg acgccgctgt tgccgttgct 154560
gctgcatcat ctactcatag aaaggttgcg tctagcacta cgcaatatga tcacaaagaa 154620
agctgtaatg gtttatatta ccagggttct tgttatatat tacattcaga ctaccagtta 154680
ttctcggatg ctaaagcaaa ttgcactgcg gaatcatcaa cactacccaa taaatccgat 154740
gtcttgacta cctggctcat tgattatgtt gaggatacat ggggatctga tggtaatcca 154800
attacaaaaa ctacatccaa ttatcaagat tctgatgtat cacaagaagt tagaaagtat 154860
ttttgtgtta aaacaatgaa ctaatattta tttttgtaca ttaataaatg aaatcgctta 154920
atagacaaac tgtaagtagg tttaagaagt tgtcggtgcc ggccgctata atgatgatac 154980
tctcaaccat tattagtggc ataggaacat ttctgcatta caaagaagaa ctgatgccta 155040
gtgcttgcgc caatggatgg atacaatacg ataaacattg ttatttagat actaacatta 155100
aaatgtctac agataatgcg gtttatcagt gtcgtaaatt acgagctaga ttgcctagac 155160
ctgatactag acatctgaga gtattgttta gtatttttta taaagattat tgggtaagtt 155220
taaaaaagac caataataaa tggttagata ttaataatga taaagatata gatattagta 155280
aattaacaaa ttttaaacaa ctaaacagta cgacggatgc tgaagcgtgt tatatataca 155340
agtctggaaa actggttaaa acagtatgta aaagtactca atctgtacta tgtgttaaaa 155400
aattctacaa gtgacaacaa aaaatgaatt aataataagt cgttaacgta cgccgccatg 155460
gacgccgcgt ttgttattac tccaatgggt gtgttgacta taacagatac attgtatgat 155520
gatctcgata tctcaatcat ggactttata ggaccataca ttataggtaa cataaaaact 155580
gtccaaatag atgtacggga tataaaatat tccgacatgc aaaaatgcta ctttagctat 155640
aagggtaaaa tagttcctca ggattctaat gatttggcta gattcaacat ttatagcatt 155700
tgtgccgcat acagatcaaa aaataccatc atcatagcat gcgactatga tatcatgtta 155760
gatatagaag ataaacatca gccattttat ctattcccat ctattgatgt ttttaacgct 155820
acaatcatag aagcgtataa cctgtataca gctggagatt atcatctaat catcaatcct 155880
tcagataatc tgaaaatgaa attgtcgttt aattcttcat tctgcatatc agacggcaat 155940
ggatggatca taattgatgg gaaatgcaat agtaattttt tatcataaaa gttgtaaagt 156000
aaataataaa acaataaata ttgaactagt agtacgtata ttgagcaatc agaaatgatg 156060
ctggtacctc ttatcacggt gaccgtagtt gcgggaacaa tattagtatg ttatatatta 156120
tatatttgta ggaaaaagat acgtactgtc tataatgaca ataaaattat catgacaaaa 156180
ttaaaaaaga taaagagttc taattccagc aaatctagta aatcaactga tagcgaatca 156240
gactgggagg atcactgtag tgctatggaa caaaacaatg acgtagataa tatttctagg 156300
aatgagatat tggacgatga tagcttcgct ggtagtttaa tatgggataa cgaatccaat 156360
gttatagcgc ctagcacaga acacatttac gatagtgttg ctggaagcac gctgctaata 156420
aataatgatc gtaatgaaca gactatttat cagaacacta cagtagtaat taatgaaacg 156480
gagactgtta aagtacttaa tgaagatacc aaacagaatc ctaactattc atccaatcct 156540
ttcgtaaatt ataataaaac cagtatttgt agcaagtcaa atccgtttat tacagaactt 156600
aacaataaat ttagtgagaa taatccgttt agacgagcac atagcgatga ttatcttaat 156660
aagcaagaac aagatcatga acacgatgat atagaatcat cggtcgtatc attggtgtga 156720
ttagtttcct ttttataaaa ttgaagtaat atttagtatt attgctgccg tcacgttgta 156780
caaatggaga tattccctgt attcggcatt tctaaaatta gcaattttat tgctaataat 156840
gactgtagat attatataga tacagaacat caaaaaatta tatctgatga gatcaataga 156900
cagatggatg aaacggtact tcttaccaac atcttaagcg tagaagttgt aaatgacaat 156960
gagatgtacc atcttattcc tcatagatta tcgacgatta tactctgtat tagttctgtc 157020
ggaggatgtg ttatctctat agataatgac atcaatgaca aaaatattct aacatttccc 157080
attgatcatg ctgtaatcat atccccactg agtaaatgtg tcgtagttag caagggtcct 157140
acaaccatat tggttgttaa agcggatata cctagcaaac gattggtaac atcgtttaca 157200
aacgacatac tatatgtaaa caatctgtca ctgattaatt atttgccgtt gtctgtattc 157260
attattagac gagtcaccga ctatttggat agacgcatat gcgatcagat atttgctaat 157320
aataagtggt attccattat aaccatcgac gataagcaat atcctattcc atcaaactgt 157380
ataggtatgt cctctgccaa gtacataaat tctagcatcg agcaagatac tttaatccat 157440
gtttgtaacc tcgagcatcc gttcgactca gtatacaaaa aaatgcagtc gtacaattct 157500
ctacctatca aggaacaaat attgtacggt agaattgata atataaatat gagcattagt 157560
atttctgtgg attaatagat ttctagtatg gggatcatta atcatctcta atctctaaat 157620
acctcataaa acgaaaaaaa agctattatc aaatactgta cggaatggat tcattctctt 157680
ctctttttat gaaactctgt tgtatatcta ctgataaaac tggaagcaaa aaatctgata 157740
aaaagaataa gaataagatc aaggattata tggaacacga ttattataaa ataacaatag 157800
ttcctggttc ctcttccacg tctactagct cgtggtatta tacacatgcc tagtaatagt 157860
ctctttgcgt tgacggaaag cagactagaa ataacaggct aaaatgttca gacaccataa 157920
tagttcccaa cccagataat aacagagttc catcaacaca ttcctttaaa ctcaatccca 157980
aacccaaaac cgttaaaatg tatccggcca attgatagta gataatgagg tgtacagcgc 158040
atgataattt acacagtaac caaaatgaaa atactttagt aattataaga aatatagatg 158100
gtaacgtcat catcaacaat ccgataatat gcctgagagt aaacattgat ggataaaaca 158160
aaaatgctcc gcataactct atcatggcaa taacacaacc aaacacttgt aaaattccta 158220
aattagtaga aaatacaacg gatatcgatg tataagtgat ctcgagaaat aataagaata 158280
aagtaatgcc cgtaaagata aacatcaaca ttgtttggta atcattaaac caattagtat 158340
gaagttgaac taatttcaca gtagatttta ttccagtgtt atcctcgcat gtataagtac 158400
ctggtaagat atctttatat tccataatca atgagacatc actatccgat aacgaatgaa 158460
gtctagcact agtatgccat ttacttaata ttgtcgtctt ggaagtttta ttataagtta 158520
aaatatcatg gttatccaat ttccatctaa tatactttgt cggattatct atagtacacg 158580
gaataatgat ggtatcatta catgctgtat actctatggt ctttgtagtt gttataacaa 158640
ccaacgtata gaggtatatc aacgatattc taactcttga cattttttat ttatttaaaa 158700
tgataccttt gttatttatt ttattctatt ttgctaacgg tattgaatgg cataagtttg 158760
aaacgagtga agaaataatt tctacttact tattagacga cgtattatac acgggtgtta 158820
atggggcggt atacacattt tcaaataata aactaaacaa aactggttta actaataata 158880
attatataac aacatctata aaagtagagg atgcggataa ggatacatta gtatgcggaa 158940
ccaataacgg aaatcccaaa tgttggaaaa tagacggttc agacgaccca aaacatagag 159000
gtagaggata cgctccttat caaaatagca aagtaacgat aatcagtcac aacggatgtg 159060
tactatctga cataaacata tcaaaagaag gaattaaacg atggagaaga tttgacggac 159120
catgtggtta tgatttatac acggcggata acgtaattcc aaaagatggt ttacgaggag 159180
cattcgtcga taaagacggt acttatgaca aagtttacat tcttttcact gatactatcg 159240
gctcaaagag aattgtcaaa attccgtata tagcacaaat gtgcctaaac gacgaaggtg 159300
gtccatcatc attgtctagt catagatggt cgacgtttct caaagtcgaa ttagaatgtg 159360
atatcgacgg aagaagttat agacaaatta ttcattctag aactataaaa acagataatg 159420
atacgatact atatgtattc ttcgatagtc cttattccaa gtccgcatta tgtacctatt 159480
ctatgaatac cattaaacaa tctttttcta cgtcaaaatt ggaaggatat acaaagcaat 159540
tgccgtctcc agctcctggt atatgtttac cagctggaaa agttgttcca cataccacgt 159600
ttgaagtcat agaaaaatat aatgtactag atgatattat aaagccttta tctaaccaac 159660
ctatcttcga aggaccgtct ggtgttaaat ggttcgatat aaaggagaag gaaaatgaac 159720
atcgggaata tagaatatac ttcataaaag aaaattctat atattcgttc gatacaaaat 159780
ctaaacaaac tcgtagctcg caagtcgatg cgcgactatt ttcagtaatg gtaacttcga 159840
aaccgttatt tatagcagat atagggatag gagtaggaat gccacaaatg aaaaaaatac 159900
ttaaaatgta atcttaatcg agtacaccac acgacaatga acaaacataa gacagattat 159960
gctggttatg cttgctgcgt aatatgcggt ctaattgtcg gaattatttt tacagcgaca 160020
ctattaaaag ttgtagaacg taaattagtt catacaccat caatagataa aacgataaaa 160080
gatgcatata ttagagaaga ttgtcctact gactggataa gctataataa taaatgtatc 160140
catttatcta ctgatcgaaa aacctgggag gaaggacgta atgcatgcaa agctctaaat 160200
ccaaattcgg atctaattaa gatagagact ccaaacgagt taagtttttt aagaagcatt 160260
agacgcggat attgggtagg agaatccgaa atattaaacc agacaacccc atataatttt 160320
atagctaaga atgccacgaa gaatggaact aaaaaacgga aatatatttg tagcacaacg 160380
aatactccca aactgcattc gtgttacact atataacaat tacactacat ttttatcata 160440
ccactacttc ggttagatgt tttagaaaaa aataaatatc gccgtaccgt tcttgttttt 160500
ataaaaataa caattaacaa ttatcaaatt ttttctttaa tattttacgt ggttgaccat 160560
tcttggtggt aaaataatct cttagtgttg gaatggaatg ctgtttaatg tttccacact 160620
catcgtatat tttgacgtat gcagtcacat cgtttacgca atagtcagac tgtagttcta 160680
tcatgcttcc tacatcagaa ggaggaacag ttttaaagtc tcttggtttt aatctattac 160740
cgttagtttt catgaaatcc tttgttttat ccacttcaca ttttaaataa atgtccacta 160800
tacattcttt tgttaatttt actagatcgt catgggtcat agaatttata ggttccgtag 160860
tccatggatc caaactagca aacttcgcgt atacggtatc gcgattagtg tatacaccaa 160920
ctgtatgaaa attaagaaaa cagtttaata gatcaacaga aatatttaat cctccgtttg 160980
atacagatgc gccatattta tggatttcgg attcacacgt tgtttgtctg aggtgttcgt 161040
ctagtgttgc ttctacgtaa acttcgattc ccatatattc tttattgtca gaatcgcata 161100
ccgatttatc atcatacact gtttgaaaac taaatggtat acacatcaaa ataacaaata 161160
ctaacgagta cattctgcaa tattgttatc gtaattggaa aaatagtgtt cgagtgagtt 161220
ggattatgtg agtattggat tgtatatttt attttatatt ttgtaataag aataaaatgc 161280
taatgtcaag tttattccaa tagatgtctt attaaaaaca tatataataa ataacaatgg 161340
ctgaatggca taaaattatc gaggatatct caaaaaataa taagttcgag gatgccgcca 161400
tcgttgatta caagactaca aagaatgttc tagctgctat tcctaacaga acatttgcca 161460
agattaatcc gggtgaaatt attcctctca tcactaatcg taatattcta aaacctctta 161520
ttggtcagaa atattgtatt gtatatacta actctctaat ggatgagaac acgtatgcta 161580
tggagttgct tactgggtac gcccctgtat ctccgatcgt tatagcgaga actcataccg 161640
cacttatatt tttgatgggt aagccaacaa catccagacg tgacgtgtat agaacgtgta 161700
gagatcacgc tacccgtgta cgtgcaactg gtaattaaaa taaaaagtaa tattcatatg 161760
tagtgtcaat tttaaatgat gatgatgaaa tgtataatat ccatattgac gatgtcaata 161820
atgccggtat tggcatacag ttcatcgatt tttagatttc attcagagga tgtggaatta 161880
tgttatgggc atttgtattt tgataggatc tataatgtag taaatataaa atataatccg 161940
catattccat atagatataa ttttattaat cgcacgttaa ccgtagatga actagacgat 162000
aatgtctttt ttacacatgg ttatttttta aaacacaaat atggttcact taatcctagt 162060
ttgattgtct cattatcagg aaacttaaaa tataatgata tacaatgctc agtaaatgta 162120
tcgtgtctca ttaaaaattt ggcaacgagt acatctacta tattaacatc taaacataag 162180
acttattctc tacatcggtc cacgtgtatt actataatag gatacgattc tattatatgg 162240
tataaagata taaatgacaa gtataatgac atctatgatt ttactgcaat atgtatgcta 162300
atagcgtcta cattgatagt gaccatatac gtgtttaaaa aaataaaaat gaactcttaa 162360
ttatgctatg ctattagaaa tggataaaat caaaattacg gttgattcaa aaattggtaa 162420
tgttgttacc atatcgtata acttggaaaa gataactatt gatgtcacac ctaaaaagaa 162480
aaaagaaaag gatgtattat tagcgcaatc agttgctgtc gaagaggcaa aagatgtcaa 162540
ggtagaagaa aaaaatatta tcgatattga agatgacgat gatatggatg tagaaagcgc 162600
gtaatactat ctataaaaat aagtatataa taaatacttt ttatttacgg tactcttgta 162660
gtggtgatac cctactcaat tattttttta aaaaaatact tattctgatt cttctaacca 162720
tttccgtgtt cgttcgaatg ccacatcgac gtcaaagata ggggagtagt tgaaatctag 162780
ttctgcattg ttggtacgca cctcaaatgt agtgttggat atcttcaacg tatagttgtt 162840
gagtagtgat ggttttctaa atagaattct cttcatatca ttcttgcacg cgtacatttt 162900
tagcatccat cttggaattc tagatccttg ttctattccc aatggtttca tcaataaaag 162960
attaaacata tcgtacgaac acgatggaga gtaatcgtag caaaagtaag catttccttt 163020
aatctcagat cccggatact ggatatattt tgcagccaac acgtgcatcc atgcaacatt 163080
tcctacatat acccggctat gcaccgcgtc atcatcgact gtacgataca taatgttacc 163140
gtgttgctta cattgctcgt aaaagacttt cgtcaatttg tctccttctc cgtaaattct 163200
agtgggtctt aggcaacaag tatacaattt tgctccattc atgattacgg aattattggc 163260
tttcataacc agttgctcgg ccatacgttt actttttgcg tatacatgtc ctggtgatat 163320
atcataaagg gtatgctcat ggccgatgaa tggatcaccg tgtttattgg gtcctattgc 163380
ttccatgcta ctagtataga tcaaatactt gattcctagg tccacacaag ctgccaaaat 163440
agtctgtgtt ccataatagt ttactttcat gatttcatta tcggtgtatt ttccaaatac 163500
atccactaga gcagccgtat gaataatcag atttacccca tctagcgctt ctctcacctt 163560
atcaaagtcg tttatatcac attgtatata gtttataacc ttaactttcg aggttattgg 163620
ttgtggatct tctacaatat ctatgactct gatttcttga acatcatctg cactaattaa 163680
cagttttact atatacctgc ctagaaatcc ggcaccacca gtaaccgcgt acacggccat 163740
tgctgccact cataatatca gactacttat tctattttac taaataatgg ctgtttgtat 163800
aatagaccac gataatatca gaggagttat ttactttgaa ccagtccatg gaaaagataa 163860
agttttagga tcagttattg gattaaaatc cggaacgtat agtttaataa ttcatcgtta 163920
cggagatatt agtcaaggat gtgattccat aggcagtcca gaaatattta tcggtaacat 163980
ctttgtaaac agatatggtg tagcatatgt ttatttagat acagatgtaa atatatctac 164040
aattattgga aaggcgttat ctatttcaaa aaatgatcag agattagcgt gtggagttat 164100
tggtatttct tacataaatg aaaagataat acattttctt acaattaacg agaatggcgt 164160
ttgatatatc agttaatgcg tctaaaacaa taaatgcatt agtttacttt tctactcagc 164220
aaaataaatt agtcatacgt aatgaagtta atgatacaca ctacactgtc gaatttgata 164280
gggacaaagt agttgacacg tttatttcat ataataaaca taatgacacc atagagataa 164340
gaggggtgct tccagaggaa actaatattg gttgcgcggt taatacgccg gttagtatga 164400
cttacttgta taataagtat agttttaaac tgattttagc agaatatata agacacagaa 164460
atactatatc cagcaatatt tattcggcat tgatgacact agatgatttg gctattaaac 164520
agtatggaga cattgatcta ttatttaatg agaaacttaa agtagactcc gattcgggac 164580
tatttgactt tgtcaacttt gtaaaggata tgatatgttg tgattctaga atagtagtag 164640
ctctatctag tctagtatct aaacattggg aattgacaaa taaaaagtat aggtgtatgg 164700
cattagccga acatatatct gatagtattc caatatctga gctatctaga ctacgataca 164760
atctatgtaa gtatctacgc gggcacactg agagcataga ggatgaattt gattattttg 164820
aagacgatga ttcgtctaca tgttctgccg taaccgacag ggaaacggat gtataatttt 164880
ttttatagcg tgaaggatat gataaaaaat ataattgttg tatttatccc attccaatca 164940
ccttatatga ttctgtaaca caataaagga gtctcataga tgtatagagg tcagatactg 165000
gtttgataaa ctgtttattc cacataagta tgtttgactt tatggttaga cccgcatact 165060
ttaacaaatc actgaaaatt ggagttaggt attgacctct cagaatcagt tgccgttctg 165120
gaacattaaa tgtatttttt atgatatact ccaacgcatt tatgtgggca tacaacaagt 165180
cattactaat ggagtattcc aagagtttta gttgtctagt atttaacaag agaagagatt 165240
tcaacagact gtttatgaac tcgaatgccg cctcattgtc gcttatattg atgatgtcga 165300
attctcccaa tatcatcacc gatgagtagc tcatcttgtt atcgggatcc aagttttcta 165360
aagatgtcat taaaccctcg atcatgaatg gatttatcat catcgttttt atgttggaca 165420
tgagcttagt ccgtttgtcc acatctatag acgacgattt ctgaattatt tcatatatcc 165480
ctctctttaa ctccaggaac ttgtcaggat ggtctacttt aatatgttct cgtctaagag 165540
atgaaaatct ttggatggtc gcatgtgact tttctctaaa ggatgacgtt gcccaagatc 165600
ctctcttaaa tgaatccatc ttatccttgg acaagatgga cagtctattt tccttagatg 165660
gtttaatatt tttgttaccc atgatctata aaggtagacc taatcgtctc ggatgaccta 165720
tatatttatt ttcagtttta ttatacgcat aaattgtaaa aaatatgtta ggtttacaaa 165780
aatgtctcgt ggggcattaa tcgtttttga aggattggac aaatctggaa aaacaacaca 165840
atgtatgaac atcatggaat caatactttc aaacacaata aaatacctta actttcctca 165900
gagatccact gtcactggaa agatgataga tgactatcta actcgtaaaa aaacctataa 165960
tgatcatata gttaatctat tattttgtgc aaatagatgg gagtttgcat cttttataca 166020
agaacaacta gaacagggaa ttactttaat agttgataga tacgcatttt ctggagtagc 166080
gtatgccgcc gctaaaggcg cgtcaatgac tctcagtaag agttatgaat ctggattgcc 166140
taaacccgac ttagttatat tcttggaatc tggtagcaaa gaaattaata gaaacgtcgg 166200
cgaggaaatt tatgaagatg ttacattcca acaaaaggta ttacaagaat ataaaaaaat 166260
gattgaagaa ggagatattc attggcaaat tatttcttct gaattcgagg aagatgtaaa 166320
gaaggagttg attaagaata tagttataga ggctatacac acggttactg gaccagtggg 166380
gcaactgtgg atgtaatagt gaaattacat tttttataaa tagatgttag tacagtgtta 166440
taaatggatg aagcatatta ctctggcaac ttggaatcag tactcggata cgtgtccgat 166500
atgcataccg aactcgcatc aatatctcaa ttagttattg ccaagataga aactatagat 166560
aatgatatat taaacaagga cattgtaaat tttatcatgt gtagatcaaa cttggataat 166620
ccatttatct ctttcctaga tactgtatat actattatag atcaagagaa ctatcagact 166680
gagttgatta attcattaga cgacaatgaa attatcgatt gtatagttaa taagtttatg 166740
agcttttata aggataacct agaaaatata gtagatgcta tcattactct aaaatatata 166800
atgaataatc cagattttaa aactacgtat gccgaagtac tcggttccag aatagccgat 166860
atagatatta aacaagtgat acgtaagaat atactacaat tgtctaatga tatccgcgaa 166920
cgatatttgt gaaaaatatt aaaaaaaaat acttttttta ttaaatgacg tcgcttcgcg 166980
aatttagaaa attatgctgt gatatatatc acgcatcagg atataaagaa aaatctaaat 167040
taattagaga ctttataaca gatagggatg ataaatattt gatcattaag ctattgcttc 167100
ccggattaga cgatagaatt tataacatga acgataaaca aattataaaa ttatatagta 167160
taatatttaa acaatctcag gaagatatgc tacaagattt aggatacgga tatataggag 167220
acactattag gactttcttc aaagagaaca cagaaatccg tccacgagat aaaagcattt 167280
taactttaga agaagtggat agtttcttaa ctacgttatc atccgtaact aaagaattgc 167340
atcaaataaa attattgact gatatcgcat ccgtttgtac atgtaatgat ttaaaatgtg 167400
tagtcatgct tattgataaa gatctaaaaa ttaaagcggg tcctcggtac gtacttaacg 167460
ctattagtcc tcatgcctat gatgtgttta gaaaatctaa taacttgaaa gagataatag 167520
aaaattcatc taaacaaaat ctagactcta tatctatttc tgttatgact ccaattaatc 167580
ccatgttagc ggaatcgtgt gattctgtca ataaagcgtt taaaaaattt ccatcaggaa 167640
tgtttgcgga agtcaaatac gatggtgaaa gagtacaagt tcataaaaat aataacgagt 167700
ttgccttctt tagtagaaac atgaaaccag tactctctca taaagtggat tatctcaaag 167760
aatacatacc gaaagcattt aaaaaagcta cgtctatcgt attggattct gaaattgttc 167820
ttgtagacga acataatgta ccgctaccgt ttggaagttt aggaatacac aaaaagaaag 167880
aatataaaaa ctctaacatg tgtttgttcg tgtttgactg tttgtacttt gatggattcg 167940
atatgacgga cattccattg tacgaacgaa gatcttttct caaagatgtt atggttgaaa 168000
tacccaatag aatagtattc tcagagttga cgaatattag taacgagtct cagttaactg 168060
acgtattgga tgatgcacta acgagaaaat tagaaggatt ggtcttaaaa gatattaatg 168120
gagtatacga accgggaaag agaagatggt taaaaataaa gcgagactat ttgaacgagg 168180
gttccatggc agattctgcc gatttagtag tactaggtgc ttactatggt aaaggagcaa 168240
agggtggtat catggcagtc tttctaatgg gttgttacga cgatgaatcc ggtaaatgga 168300
agacggttac caagtgttca ggacacgatg ataatacgtt aagggagttg caagaccaat 168360
taaagatgat taaaattaac aaggatccca aaaaaattcc agagtggtta gtagttaata 168420
aaatctatat tcccgatttt gtagtagagg atccgaaaca atctcagata tgggaaattt 168480
caggagcaga gtttacatct tccaagtccc ataccgcaaa tggaatatcc attagatttc 168540
ctagatttac taggataaga gaggataaaa cgtggaaaga atctactcat ctaaacgatt 168600
tagtaaactt gactaaatct taatagttac atacaaacta aaaattaaaa taacactatt 168660
tagttggtgg tcgccatgga tggtgttatt gtatactgtc taaacgcgct agtaaaacat 168720
ggcgaggaaa taaatcatat aaaaaatgat ttcatgatta aaccatgttg tgaaagagtt 168780
tgtgaaaaag tcaagaacgt tcacatcggc ggacaatcta aaaacaatac agtgattgca 168840
gatttgccat atctggataa tgctgtatcc gatgtatgca aatcgatata tatatagtat 168900
caagaatatc cagatttgct aatttgataa agatagatga cgatgacaag actcctactg 168960
gtgtatataa ttattttaaa cttaaagatg ccattcctgt tattatatct ataggaaagg 169020
ataaagatgt ctgtgaacta ttaatctcat cagacatatc gtgtgcatgc gtggagttaa 169080
attcatatca cgtagccatt cttcccatgg atgtttcctt ttttaccaaa ggaaatgcat 169140
cattgattat tctcctgttt gatttctcta tcgatgcggc acctctctta agaagtgtaa 169200
ccgataataa tgttattata tctagacacc agcgtctaca tgacgagctt ccgagttcca 169260
attggttcaa gttttacata agtataaagt ccgactattg ttctatatta tatatggttg 169320
ttgatggatc tgtgatgcat gcgatagctg ataatagaac tcacgcaatt attagcaaaa 169380
atatattaga caatactacg attaacgatg agtgtagatg ctgttatttt gaaccacaga 169440
ttaggattct tgatagagat gagatgctca atggatcatc gtgtgatatg aacagacatt 169500
gtattatgat gaatttacct gatgtaggcg aatttggatc tagtatgttg gggaaatatg 169560
aacctgacat gattaagatt gctctttcgg tggctggtaa tttaataaga aatcgagact 169620
acattcccgg gagacgagga tatagctact acgtttacgg tatagcctct agataatttt 169680
tttaagcacg aaataaaaaa cataatttta aaccaatcta tttcatacta ttttgtgtga 169740
tcaccatgga cataaagata gatattagta tttctggtga taaatttacg gtgactacta 169800
ggagggaaaa tgaagaaaga aaaaaatatc tacctctcca aaaagaaaaa actactgatg 169860
ttatcaaacc tgattatctt gagtacgatg acttgttaga tagagatgag atgtttacta 169920
ttctagagga atattttatg tacagaggtc tattaggcct cagaataaaa tatggacgac 169980
tctttaacga aattaaaaaa ttcgacaatg atgcggaaga acaattcggt actatagaag 170040
aactcaagca gaaacttaga ttaaattctg aagagggagc agataacttt atagattata 170100
taaaggtaca aaaacaggat atcgtcaaac ttactgtata cgattgcata tctatgatag 170160
gattgtgtgc atgcgtggta gatgtttgga gaaatgagaa actgttttct agatggaaat 170220
attgtttacg agcgattaaa ctgtttattg atgatcacat gcttgataag ataaaatcta 170280
tactgcagaa tagactagtg tatgtggaaa tgtcatagaa agttaatgag agcaaaaata 170340
tataaggttg tattccatat ttgttatttt tttctgtaat agttagaaaa atacattcga 170400
tggtctatct atcagattat tatgtgttat aaggtacttt ttctcataat aaactagagt 170460
atgagtaaga tagtgttttt caaaacatat aaatctaaaa ttgatggatg agatatacag 170520
ctattaattt cgaaaatata ttttaatctg ataactttaa acatggattt ttgatggtgg 170580
tttaacgttt taaaaaaaga ttttgttatt gtagtatatg ataatattaa aagatggata 170640
taaagaattt gctgactgta tgtactattt tttacattac tacattggct acggcagata 170700
tacctactcc gccaccaacg gggcatgtga cgagggagaa tatcttgata agaggcataa 170760
tcaatgttgt aatcggtgtc cacctggaga atttgccaag gtcagatgta gtggtagtga 170820
taacacaaaa tgtgaacgct gcccacctca tacatatacc gcaatcccca attactctaa 170880
tggatgtcat caatgtagaa aatgcccaac aggatcattt gataaggtaa agtgtaccgg 170940
aacacagaac agtaaatgtt cgtgtcttcc tggttggtat tgcgctactg attcttcaca 171000
gactgaagat tgtcgagatt gtataccaaa aaggagatgt ccatgcggat actttggtgg 171060
aatagatgaa caaggaaatc ctatttgtaa atcgtgttgt gttggtgaat attgcgacta 171120
cctacgtaat tatagacttg atccatttcc tccatgcaaa ctatctaaat gtaattaatt 171180
atgattttga tgataatgtt accatacatt atatcgctac ttggttagtg tattattcag 171240
tatgaagacc tattaataat tacttatctt ttgacgatct tgttataatt ataatataaa 171300
aacttatggc atagtaactt ataattgctg acgcgataaa ttcgtaataa tctgttttgt 171360
tcaaaggaat ctacaggcat aaaaataaaa atataattta taatatactc ttacagcgcg 171420
ccatcatgaa taacagcagt gaattgattg ctgttattaa tggatttaga aatagtggac 171480
gattttgtga tattagtata gttattaatg atgaaaggat aaacgctcat aaactcatcc 171540
tatctggagc ctccgaatat ttttccattc tgttttccaa taattttatc gattctaatg 171600
aatacgaagt taatctaagt catttagatt atcaaagtgt taacgatttg atcgattata 171660
tttatgggat acctttgagc ctaactaacg ataacgtgaa atatattctt tcaaccgctg 171720
attttttaca aattggatct gccattactg agtgcgaaaa atacatactt aaaaatcttt 171780
gttctagaaa ctgtatcgat ttctacatat acgctgataa atataataac aagaaaatag 171840
aatcagcgtc gtttaacaca atattacaaa atattttgag actcatcaac gatgaaaact 171900
ttaaatactt aacagaggaa tcaatgataa aaattttaag cgatgatatg ttaaatataa 171960
aaaatgagga tttcgcccca ctaattctca ttaaatggtt agagagtact caacaatcat 172020
gcaccgtcga gttacttaga tgcctcagaa tatcattgct ttccccacaa gttataaaat 172080
cactttatag tcatcgactg gttagttcaa tctacgaatg tataacattc ttaaacaata 172140
tagcattctt ggatgaatca tttcctagat accatagcat cgagttgata tctatcggta 172200
taagtaattc gcatgataag atttccataa actgctacaa tcataaaaaa aatacatggg 172260
aaatgatatc ttcacgtaga tataggtgta gtttcgcagt ggccgtcctg gataatatta 172320
tttatatgat gggtggatat gatcagtccc cgtatagaag ttcaaaggtt atagcgtaca 172380
atacatgtac aaattcttgg atatatgata taccagagct aaaatatcct cgttctaatt 172440
gtgggggact ggctgatgac gaatacattt attgtatagg cggcatacgc gatcaggatt 172500
catcgttgac atctagtatt gatagatgga agccatcaaa accatattgg cagaagtatg 172560
ctaaaatgcg cgaaccaaaa tgtgatatgg gggttgcgat gttaaacgga ttaatatatg 172620
tcatgggtgg aatcgttaaa ggtgacacgt gtaccgacgc actagagagt ttatcagaag 172680
atggatggat gaagcatcaa cgtcttccaa taaaaatgtc caatatgtcg acgattgttc 172740
atgatggcaa gatttatata tctggaggtt acaacaatag tagtgtagtt aatgtaatat 172800
cgaatctagt ccttagctat aattcgatat atgatgaatg gaccaaatta tcatcattaa 172860
acattcctag aattaatccc gctctatggt cagcgcataa taaattatat gtaggaggag 172920
gaatatctga tgatgttcga actaatacat ctgagacata cgacaaagaa aaagattgtt 172980
ggacattgga taatggtcac gtgttaccac gcaattatat aatgtataaa tgcgaaccga 173040
ttaaacataa atatccattg gaaaaaacac agtacacgaa tgattttcta aagtatttgg 173100
aaagttttat aggtagttga tagaacaaaa tacataattt tgtaaaaata aatcactttt 173160
tatactaata tgacacgatt accaatactt ttgttactaa tatcattagt atacgctaca 173220
ccttctcctc agacatctaa aaaaataggt gatgatgcaa ctctatcatg taatcgaaat 173280
aatacaaatg actacgttgt tatgagtgct tggtataagg agcccaattc cattattctt 173340
ttagctgcta aaagcgacgt cttgtatttt gataattata ccaaggataa aatatcttac 173400
gactctccat acgatgatct agttacaact atcacaatta aatcattgac tgctagagat 173460
gccggtactt atgtatgtgc attctttatg acatcgccta caaatgacac tgataaagta 173520
gattatgaag aatactccac agagttgatt gtaaatacag atagtgaatc gactatagac 173580
ataatactat ctggatctac acattcaccg gaaactagtt ctgagaaacc tgattatata 173640
gataattcta attgctcgtc ggtattcgaa atcgcgactc cggaaccaat tactgataat 173700
gtagaagatc atacagacac cgtcacatac actagtgata gcattaatac agtaagtgca 173760
tcatctggag aatccacaac agacgagact ccggaaccaa ttactgataa agaagaagat 173820
catacagtca cagacactgt ctcatacact acagtaagta catcatctgg aattgtcact 173880
actaaatcaa ccaccgatga tacgtacaat gataatgata cagtaccacc aactactgta 173940
ggcggtagta caacctctat tagcaattat aaaaccaagg actttgtaga aatatttggt 174000
attaccgcat taattatatt gtcggccgtg gcaatattct gtattacgta ttatatatgt 174060
aataaacgtt cacgtaaata caaaacagag aacaaagtct agatttttga cttacataaa 174120
tgtctgggat agtaaaatct atcatattga gcggaccatc tggtttagga aagacagcca 174180
tagccaaaag actatgggaa tatatttgga tttgtggtgt cccataccac tagatttcct 174240
cgtcctatgg aacgagaagg tgtcgattac cattacgtta acagagaggc catctggaag 174300
ggaatagccg ccggaaactt tctagaacat actgagtttt taggaaatat ttacggaact 174360
tctaaaactg ctgtgaatac agcggctatt aataatcgta tttgtgtgat ggatctaaac 174420
atcgatggcg ttagaagtct taaaaatacg tacctaatgc cttactcggt gtatataaga 174480
cctacctctc ttaaaatggt tgagaccaag cttcgtcgta gaaacactga agcggatgat 174540
gagattcatc gtcgtgtgat gttggcaaaa actgacatgg atgaggcagg tgaagccggt 174600
ctattcgaca ctattattat tgaagatgat gtgaatttag catatagtaa gttaattcag 174660
atactacagg accgtattag aatgtatttt aacactaatt agagacttaa gacttaaaac 174720
ttgataatta ataatataac tcgtttttat atgtgtctat ttcaacgtct aatgtattag 174780
ttaaatatta aaacttacca cgtaaaactt aaaatttaaa atgatatttc attgacagat 174840
agatcacaca ttatgaactt tcaaggactt gtgttaactg acaattgcaa aaatcaatgg 174900
gtcgttggac cattaatagg aaaaggtgga ttcggtagta tttatactac taatgacaat 174960
aattatgtag taaaaataga gcccaaagct aacggatcat tatttaccga acaggcattt 175020
tatactagag tacttaaacc atccgttatc gaagaatgga aaaaatctca caatataaag 175080
cacgtaggtc ttatcacgtg caaggcattt ggtctataca aatccattaa tgtggaatat 175140
cgattcttgg taattaatag attaggtgca gatctagatg cggtgatcag agccaataat 175200
aatagattac caaaaaggtc ggtgatgttg atcggaatcg aaatcttaaa taccatacaa 175260
tttatgcacg agcaaggata ttctcacgga gatattaaag cgagtaatat agtcttggat 175320
caaatagata agaataaatt atatctagtg gattacggat tggtttctaa attcatgtct 175380
aatggcgaac atgttccatt tataagaaat ccaaataaaa tggataacgg tactctagaa 175440
tttacaccta tagattcgca taaaggatac gttgtatcta gacgtggaga tctagaaaca 175500
cttggatatt gtatgattag atggttggga ggtatcttgc catggactaa gatatctgaa 175560
acaaagaatt gtgcattagt aagtgccaca aaacagaaat atgttaacaa tactgcgact 175620
ttgttaatga ccagtttgca atatgaacct agagaattgc tgcaatatat taccatggta 175680
aactctttga catattttga ggaacccaat tacgacaagt ttcggcacat attaatgcag 175740
ggtgtatatt attaagtgtg gtgtttggtc gatgtaaaat ttttgtcgat aaaaattaaa 175800
aaataactta atttattatt gatctcgtgt gtacaaccga aatcatggcg atgttttacg 175860
cacacgctct cggtgggtac gacgagaatc ttcatgcctt tcctggaata tcatcgactg 175920
ttgccaatga tgtcaggaaa tattctgttg tgttagttta taataacaag tatgacattg 175980
taaaagacaa atatatgtgg tgttacagtc aggtgaacaa gagatatatt ggagcactgc 176040
tgcctatgtt tgagtgcaat gaatatctac aaattggaga tccgatccat gatcaagaag 176100
gaaatcaaat ctctatcatc acatatcgcc acaaaaacta ctatgctcta agcggaatcg 176160
ggtacgagag tctagacttg tgtttggaag gagtagggat tcatcatcac gtacttgaaa 176220
caggaaacgc tgtatatgga aaagttcaac atgattattc tactatcaaa gagaaggcca 176280
aagaaatgag tacacttagt ccaggaccta tcatcgatta ccacgtctgg ataggagatt 176340
gtatctgtca agttactgct gtggacgtac atggaaagga aattatgaga atgagattca 176400
aaaagggtgc ggtgcttccg atcccaaatc tggtaaaagt taaacttggg gagaatgata 176460
cagaaaatct ttcttctact atatcggcgg caccatcgag gtaaccacct ctctggaaga 176520
cagcgtgaat aatgtactca tgaaacgttt ggaaactata cgccatatgt ggtctgtcgt 176580
atatgatcat tttgatattg tgaatggtaa agaatgctgt tatgtgcata cgcatttgtc 176640
taatcaaaat cctataccga gtactgtaaa aacaaatttg tacatgaaga ctatgggatc 176700
atgcattcaa atggattcca tggaatctct agagtatctt agcgaactga aggaatcagg 176760
tggatggagt cccagaccag aaatgcagga atttgaatat ccagatggag tggaagacac 176820
tgaatcaatt gagagattgg tagaggagtt cttcaataga tcagaacttc aggctggtga 176880
atcagtcaaa tttggtaatt ctattaattg ttaaacatac atctgtttca gctaagcaac 176940
taagaacacg tatacggcag cagcttcctt tatactctca tcttttacca acacaaaggg 177000
tggatatttg ttcattggag ttgataataa tacacacaaa gtatttggat tcacggtggg 177060
ttacgactac ctcagactga tagagaatga tatagaaaag catatcaaaa gactttgtgt 177120
tgtgtatttc tgtgagaaga aagaggacat caagtacgcg tgtcgattca tcaaggtata 177180
taaacctggg gatgagacta ccttgacata cgtgtgcgct atcaaagtgg aaagatgctg 177240
ttgtgctgtg tttgcagatt ggccagaatc atggtatatg gatactaatg gtatcaagaa 177300
gtattctcca gatgaatggg tgtcacatat aaaattttaa ttaatgtaat agagaacaaa 177360
taataaggtt gtaatatcat atagacaata actaacaatt aattagtaac tgttatctct 177420
tttttaacta accaactaac tatataccta ttaatacatc gtaattatag ttcttaacat 177480
ctattaatca ttaattcgct tctttaattt tttataaact aacattgtta attgaaaagg 177540
gataacatgt tacagaatat aaattatata tggatttttt taaaaaggaa atacttgact 177600
ggagtatata tttatctctt cattatatag cacgcgtgtt ttccaatttt tccacatccc 177660
atataataca ggattataat ctcgttcgaa catacgagaa agtggataaa acaatagttg 177720
attttttatc taggttgcca aatttattcc atattttaga atatggggaa aatattctac 177780
atatttattc tatggatgat gctaatacga atattataat tttttttcta gatagagtat 177840
taaatattaa taagaacggg tcatttatac acaatctcgg gttatcatca tccattaata 177900
taaaagaata tgtatatcaa ttagttaata atgatcatcc agataatagg ataagactaa 177960
tgcttgaaaa tggacgtaga acaagacatt ttttgtccta tatatcagat acagttaata 178020
tctatatatg tattttaata aatcatggat tttatataga tgccgaagac agttacggtt 178080
gtacattatt acatagatgt atatatcact ataagaaatc agaatcagaa tcatacaatg 178140
aattaattaa gatattgtta aataatggat ccgatgtaga taaaaaagat acgtacggaa 178200
acacaccttt tatcctatta tgtaaacacg atatcaacaa cgtggaattg tttgagatat 178260
gtttagagaa tgctaatata gactctgtag actttaatag atatacacct cttcattatg 178320
tctcatgtcg taataaatat gattttgtaa agttattaat ttctaaagga gcaaatgtta 178380
atgcgcgtaa tagattcgga actactccat tttattgtgg aattatacac ggtatctcgc 178440
ttataaaact atatttggaa tcagacacag agttagaaat agataatgaa catatagttc 178500
gtcatttaat aatttttgat gctgttgaat ctttagatta tctattatcc agaggagtta 178560
ttgatattaa ctatcgtact atatacaacg aaacatctat ttacgacgct gtcagttata 178620
atgcgtataa tacgttggtc tatctattaa acaaaaatgg tgattttgag acgattacta 178680
ctagtggatg tacatgtatt tcggaagcag tcgcaaacaa caacaaaata ataatggaag 178740
tactattgtc taaacgacca tctttgaaaa ttatgataca gtctatgata gcaattacta 178800
aacataaaca gcataatgca gatttattga aaatgtgtat aaaatatact gcgtgtatga 178860
ccgattatga tactcttata gatgtacagt cgctacagca atataaatgg tatattttaa 178920
gatgtttcga tgaaatagat atcatgaaga gatgttatat aaaaaataaa actgtattcc 178980
aattagtttt ttgtatcaaa gacattaata ctttaatgag atacggtaaa catccttctt 179040
tcgtgaagtg cactagtctc gacgtatacg gaagtcgtgt acgtaatatc atagcatcta 179100
ttagatatcg tcagagatta attagtctat tatccaagaa gctggatgcg ggagataaat 179160
ggtcgtgttt tcctaacgaa ataaaatata aaatattgga aaactttaac gataacgaac 179220
tatccacata tctaaaaatc ttataaacat tattaaaata taaaatctaa gtggataaaa 179280
tcacactaca tcattgtttc cttttagtgc tcgacagtgt atactatttt taacgctcat 179340
aaataaaaat gaaaacgatt tccgttgtta cgttgttatg cgtactacct gctgttgttt 179400
attcaacatg tactgtaccc actatgaata acgctaaatt aacgtctacc gaaacatcgt 179460
ttaatgataa acagaaagtt acatttacat gtgatcaggg atatcattct ttggatccaa 179520
atgctgtctg tgaaacagat aaatggaaat acgaaaatcc atgcaagaaa atgtgcacag 179580
tttctgatta tgtctctgaa ttatatgata agccattata cgaagtgaat tccaccatga 179640
cactaagttg caacggcgaa acaaaatatt ttcgttgcga agaaaaaaat ggaaatactt 179700
cttggaatga tactgttacg tgtcctaatg cggaatgtca acctcttcaa ttagaacacg 179760
gatcgtgtca accagttaaa gaaaaatact catttgggga atatatgact atcaactgtg 179820
atgttggata tgaggttatt ggtgcttcgt acataagttg tacagctaat tcttggaatg 179880
ttattccatc atgtcaacaa aaatgtgata tgccgtctct atctaacgga ttaatttccg 179940
gatctacatt ttctatcggt ggcgttatac atcttagttg taaaagtggt tttacactaa 180000
cggggtctcc atcatccaca tgtatcgacg gtaaatggaa tcccatactc ccaacatgtg 180060
tacgatctaa cgaaaaattt gatccagtgg atgatggtcc cgacgatgag acagatttga 180120
gcaaactctc gaaagacgtt gtacaatatg aacaagaaat agaatcgtta gaagcaactt 180180
atcatataat catagtggcg ttaacaatta tgggcgtcat atttttaatc tccgttatag 180240
tattagtttg ttcctgtgac aaaaataatg accaatataa gttccataaa ttgctaccgt 180300
aaatataaat ccgttaaaat aattaataat taataacgaa caagtatcaa aagattaaag 180360
acttatagct agaatcaatt gagatgtctt cttcagtgga tgttgatatc tacgatgccg 180420
ttagagcatt tttactcagg cactattata acaagagatt tattgtgtat ggaagaagta 180480
acgccatatt acataatata tacaggctat ttacaagatg cgccgttata ccgttcgatg 180540
atatagtacg tactatgcca aatgaatcac gtgttaaaca atgggtgatg gatacactta 180600
atggtataat gatgaatgaa cgcgatgttt ctgtaagcgt tggcaccgga atactattca 180660
tggaaatgtt tttcgattac aataaaaata gtatcaacaa tcaactaatg tatgatataa 180720
ttaatagcgt atctataatt ctagctaatg agagatatag aagcgctttt aacgacgatg 180780
gtatatacat ccgtagaaat atgattaaca agttgtacgg atacgcatct ctaactacta 180840
ttggcacgat cgctggaggt gtttgttatt atctgttgat gcatctagtt agtttgtata 180900
aataattatt tcaatatact agttaaaatt ttaagatttt aaatgtataa aaaactaata 180960
acgtttttat ttgtaatagg tgcattagca tcctattcga ataatgagta cactccgttt 181020
aataaactga gtgtaaaact ctatatagat ggagtagata atatagaaaa ttcatatact 181080
gatgataata atgaattggt gttaaatttt aaagagtaca caatttctat tattacagag 181140
tcatgcgacg tcggatttga ttccatagat ataaatgtta taaacgacta taaaattatt 181200
gatatgtata ccattgactc gtctactatt caacgcagag gtcacacgtg tagaatatct 181260
accaaattat catgccatta tgataagtac ccttatattc acaaatatga tggtgatgag 181320
cgacaatatt ctattactgc agagggaaaa tgctataaag gaataaaata tgaaataagt 181380
atgatcaacg atgatactct attgagaaaa catactctta aaattggatc tacttatata 181440
tttgatcgtc atggacatag taatacatat tattcaaaat atgattttta aaaatttaaa 181500
atatattatc acttcagtga cagtagtcaa ataacaaaca acaccatgag atatattata 181560
attctcgcag ttttgttcat taatagtata catgctaaaa taactagtta taagtttgaa 181620
tccgtcaatt ttgattccaa aattgaatgg actggggatg gtctatacaa tatatccctt 181680
aaaaattatg gcatcaagac gtggcaaaca atgtatacaa atgtaccaga aggaacatac 181740
gacatatccg catttccaaa gaatgatttc gtatctttct gggttaaatt tgaacaaggc 181800
gattataaag tggaagagta ttgtacggga ctatgcgtcg aagtaaaaat tggaccaccg 181860
actgtaacat tgactgaata cgacgaccat atcaatttgt acatcgagca tccgtatgct 181920
actagaggta gcaaaaagat tcctatttac aaacgcggtg acatgtgtga tatctacttg 181980
ttgtatacgg ctaacttcac attcggagat tctaaagaac cagtaccata tgatatcgat 182040
gactacgatt gcacgtctac aggttgcagc atagactttg tcacaacaga aaaagtgtgc 182100
gtgacagcac agggagccac agaagggttt ctcgaaaaaa ttactccatg gagttcgaaa 182160
gtatgtctga cacctaaaaa gagtgtatat acatgcgcaa ttagatccaa agaagatgtt 182220
cccaatttca aggacaaaat ggccagagtt atcaagagaa aatttaatac acagtctcaa 182280
tcttatttaa ctaaatttct cggtagcaca tcaaatgatg ttaccacttt tcttagcatg 182340
cttaacttga ctaaatattc ataactaatt tttattaatg atacaaaaac gaaataaaac 182400
tgcatattat acactggtta acgcccttat aggctctaac cattttcaag atgaggtccc 182460
tgattatagt ccttctgttc ccctctatca tctactccat gtctattaga caatgtgaga 182520
aaactgaaga ggaaacatgg ggattgaaaa tagggttgtg tataattgcc aaagatttct 182580
atcccgaaag aactgattgc agtgttcatc tcccaactgc aagtgaagga ttgataactg 182640
aaggcaatgg attcagggat atacgaaaca ccgataaatt ataaaaaaag caatgtgtcc 182700
gctgtttccg ttaataatac tatttttgta actggcggat tattcataaa taactctaat 182760
agcacgatcg tggttaacaa tatggaaaaa cttgacattt ataaagacaa acaatggtcg 182820
attatagaaa tgcctatggc tagggtatat cacggcatcg actcgacatt tggaatgtta 182880
tattttgccg gaggtctatc cgttaccgaa caatatggta atttagagaa aaacaacgag 182940
atatcttgtt acaatcctag aacgaataag tggtttgata tttcatatac tatttataag 183000
atatccatat catcattgtg taaactaaat aacgtcttct atgtatttag taaggacatt 183060
ggatatgtgg aaaagtatga tggtgcatgg aagttagtac atgatcgtct ccccgctata 183120
aaggcattat caacttctcc ttattgattg aaaatgaaaa tataaatagt ttttatgtat 183180
agcagtatta ccctatagtt ttattgctta ctactaacat ggatacagat gttacaaatg 183240
tagaagatat cataaatgaa atagatagag agaaagaaga aatactaaaa aatgtagaaa 183300
ttgaaaataa taaaaacatt aacaagaatc atccaagtgg atatattaga gaagcactcg 183360
ttattaatac cagtagtaat agtgattcca ttgataaaga agttatagaa tgtatctgtc 183420
acgatgtagg aatatagatc atatctacta atttttataa tcgatacaaa acataaaaaa 183480
caactcgtta ttacatagca ggcatggaat ccttcaagta ttgttttgat aacgatggca 183540
agaaatggat tatcggaaat actttatatt ctggtaattc aatactctat aaggtcagaa 183600
aaaatttcac tagttcgttc tacaattacg taatgaagat agatcacaaa tcacacaagc 183660
cattgttgtc tgaaatacga ttctatatat ctgtattgga tcctttgact atcgacaact 183720
ggacacggga acgtggtata aagtatttgg ctattccaga tctgtatgga attggagaaa 183780
ccgatgatta tatgttcttc gttataaaga attcgggaag agtattcgcc ccaaaggata 183840
ctgaatcagt cttcgaagca tgcgtcacta tgataaacac gttagagttt atacactctc 183900
gaggatttac ccatggaaaa atagaaccga ggaatatact gattagaaat aaacgtcttt 183960
cactaattga ctattctaga actaacaaac tatacaagag tggaaactca catatagatt 184020
acaacgagga catgataact tcaggaaata tcaattatat gtgtgtagac aatcatcttg 184080
gagcaacagt ttcaagacga ggagatttag aaatgttggg atattgcatg atagaatggt 184140
tcggtggcaa acttccatgg aaaaacgaaa gtagtataaa agtaataaaa caaaaaaaag 184200
aatataaaaa atttatagct actttctttg aggactgttt tcctgaagga aatgaacctc 184260
tggaattagt tagatatata gaattagtat acacgttaga ttattctcaa actcctaatt 184320
atgacagact acgtaaactg tttatacaag attgaaatta tattcttttt ttatagagtg 184380
tggtagtgtt acggatattt aatattagac tatctctatc gcgctacacg accaatatcg 184440
attactatgg atatcttcta tgaaaggaga gaatgtattc atttctccag cgtcaatctc 184500
gtcagtattg acaatactgt attatggagc taatggatcc actgctgaac agctatcgaa 184560
atatgtagaa aaggaggaga acacggataa ggttagcgct cagaatatct cattcaaatc 184620
catgaataaa gtatatgggc gatattctgc cgtgtttaaa gattcctttt tgagaaaaat 184680
tggcgataag tttcaaactg ttgacttcac tgattgtcgc actatagatg caatcaacaa 184740
gtgtgtagat atctttactg aggggaaaat caatccacta ttggatgaac cattgtctcc 184800
tagcaattag tgccgtatac tttaaagcaa aatggttgac gccattcgaa aaggaattta 184860
ccagtgatta tcccttttac gtatcaccaa cggaaatggt agacgtaagt atgatgtcta 184920
tgtacggcga gctatttaat cacgcatctg taaaagaatc attcggcaac ttttcaatca 184980
tagaactgcc atatgttgga gatactagta tgatggtcat tcttccagac aagattgatg 185040
gattagaatc catagaacaa aatctaacag atacaaattt taagaaatgg tgtgacttta 185100
tggatgctat gtttatagat gttcacattc ccaagtttaa ggtaacaggt tcgtataatc 185160
tggtggatac tctagtaaag tcaggactga cagaggtgtt cggttcaact ggagattata 185220
gcaatatgtg taattcagat gtgagtgtcg acgctatgat ccacaaaacg tatatagatg 185280
tcaatgaaga gtatacagaa gcagctgcag caacttctgt actagtggca gactgtgcat 185340
caacagttac aaatgagttc tgtgcagatc atccgttcat ctatgtgatt aggcatgttg 185400
atggaaaaat tcttttcgtt ggtagatatt gctctccgac aactaattgt taaccatttt 185460
ttttaaaaaa aatagaaaaa acatgtggta ttagtgcagg tcgttattct tccaattgca 185520
attggtaaga tgacggccaa ctttagtacc cacgtctttt caccacagca ctgtggatgt 185580
gacagactga ccagtattga tgacgtcaaa caatgtttga ctgaatatat ttattggtcg 185640
tcctatgcat accgcaacag gcaatgcgct ggacaattgt attccacact cctctctttt 185700
agagatgatg cggaattagt gttcatcgac attcgcgagc tggtaaaaaa tatgccgtgg 185760
gatgatgtca aagattgtac agaaatcatc cgttgttata taccggatga gcaaaaaacc 185820
atcagagaga tttcggccat catcggactt tgtgcatatg ctgctactta ctggggaggt 185880
gaagaccatc ccactagtaa cagtctgaac gcattgtttg tgatgcttga gatgctaaat 185940
tacgtggatt ataacatcat attccggcgt atgaattgat gagttgtaca tcttgacatt 186000
ttctttcttc tcttctccct ttcttctctt ctcccttcct ccctcttctc cctttcccag 186060
aaacaaactt ttttacccac tataaaataa aatgagtata ctacctatta tatttcttcc 186120
tatatttttt tattcttcat tcgttcagac ttttaacgcg cctgaatgta tcgacaaagg 186180
gcaatatttt gcatcattca tggagttaga aaacgagcca gtaatcttac catgtcctca 186240
aataaatacg ctatcatccg gatataatat attagatatt ttatgggaaa aacgaggagc 186300
ggataatgat agaattatac cgatagataa tggtagcaat atgctaattc tgaacccgac 186360
acaatcagac tctggtattt atatatgcat taccacgaac gaaacctact gtgacatgat 186420
gtcgttaaat ttgacaatcg tgtctgtctc agaatcaaat atagatctta tctcgtatcc 186480
acaaatagta aatgagagat ctactggcga aatggtatgt cccaatatta atgcatttat 186540
tgctagtaac gtaaacgcag atattatatg gagcggacat cgacgcctta gaaataagag 186600
acttaaacaa cggacacctg gaattattac catagaagat gttagaaaaa atgatgctgg 186660
ttattataca tgtgttttag aatatatata cggtggcaaa acatataacg taaccagaat 186720
tgtaaaatta gaggtacggg ataaaataat accttctact atgcaattac cagatggcat 186780
tgtaacttca ataggtagta atttgactat tgcatgcaga gtatcgttga gacctcccac 186840
aacggacacc gacgtctttt ggataagtaa tggtatgtat tacgaagaag atgatgggga 186900
cggaaacggt agaataagtg tagcaaataa aatctatatg accgataaga gacgtgttat 186960
tacatcccgg ttaaacatta atcctgtcaa ggaagaagat gctacaacgt ttacgtgtat 187020
ggcgtttact attcctagca tcagcaaaac agttactgtt agtataacgt gaatgtatgt 187080
tgttacattt ccatgtcaat tgagtttata agaattttta tacattatct tccaacaaac 187140
aattgacgaa cgtattgcta tgattaactc ccacgatact atgcatatta ttaatcatta 187200
acttgcagac tatacctagt gctattttga catactcatg ttcttgtgta attgcggtat 187260
ctatattatt aaagtacgta aatctagcta tagttttatt atttaatttt agataatata 187320
ccgtctcctt atttttaaaa attgccacat cctttattaa atcatgaatg ggaatttcta 187380
tgtcatcgtt agtatattgt gaacaacaag agcagatatc tataggaaag ggtggaatgc 187440
gatacattga tctatgtagt tttaaaacac acgcaaactt tgaagaattt atataaatca 187500
ttccatcgat acatccttct atgttgagat gtatatatcc aggaattcgt ttattaatat 187560
cgggaaatgt ataaactaaa acattgcccg aaagcggtgc ctctatctgc gttatatccg 187620
ttcttaactt acaaaatgta accaatacct ttgcatgact tgttttgttc ggcaacgtta 187680
gtttaaactt gacgaatgga ttaattacaa tagcatgatc cgcgcatcta ttaagttttt 187740
ttactttaac gcccttgtat gtttttacag agactttatc taaatttcta gtgcttgtat 187800
gtgttataaa tataacggga tatagaactg aatcacctac cttagatacc caattacatt 187860
ttatcagatc cagataataa acaaattttg tcgccctaac taattctata ttgttatata 187920
ttttacaatt ggttatgata tcatgtaata acttggagtc taacgcgcat cgtcgtacgt 187980
ttatacaatt gtgatttagt gtagtatatc tacacatgta tttttccgca ctatagtatt 188040
ctggactagt gataaaacta tcgttatatc tatcttcaat gaactcatcg agatattgct 188100
ctctgtcata ttcatacacc tgcataaact ttctagacat cttacaatcc gtgttatttt 188160
aggatcatat ttacatattt acgggtatat caaagatgtt agattagtta atgggaatcg 188220
tctataataa tgaatattaa acaattatat gaggactttt accacaaagc atcataaaaa 188280
tgagtcgtcg tctgatttat gttttaaata tcaaccgcga atcaactcat aaaatacaag 188340
agaatgaaat atatacatat tttagtcatt gcaatataga ccatacttct acagaacttg 188400
attttgtagt taaaaactat gatctaaaca gacgacaaca tgtaactggg tatactgcac 188460
tacactgcta tttgtataat aattacttta caaacgatgt actgaagata ttattaaatc 188520
atggagtgga tgtaacgatg aaaaccagta gcggacgtat gcctgtttat atattgctta 188580
ctagatgttg taatatttca catgatgtag tgatagatat gatagacaaa gataaaaacc 188640
acttattaca tagagactat tccaacctat tactagagta tataaaatct cgttacatgt 188700
tattgaagga agaggatatc gatgagaaca tagtatccac tttattagat aagggaatcg 188760
atcctaactt taaacaagac ggatatacag cgttacatta ttattatttg tgtctcgcac 188820
acgtttataa accaggtgag tgtagaaaac cgataacgat aaaaaaggcc aagcgaatta 188880
tttctttgtt tatacaacat ggagctaatc taaacgcgtt agataattgt ggtaatacac 188940
cattccattt gtatcttagt attgaaatgt gtaataatat tcatatgact aaaatgctgt 189000
tgacttttaa tccgaatttc gaaatatgta ataatcatgg attaacgcct atactatgtt 189060
atataacttc cgactacata caacacgata ttcttgttat gttaatacat cactatgaaa 189120
caaatgttgg agaaatgccg atagatgagc gtcgtatgat cgtattcgag tttatcaaaa 189180
catattctac acgtccggca gattcgataa cttatttgat gaataggttt aaaaatataa 189240
atatttatac ccgctatgaa ggaaagacat tattacacgt agcatgtgaa tataataata 189300
cacaagtaat agattatctt atacgtatca acggagatat aaatgcgtta accgacaata 189360
acaaacacgc tacacaactc attatagata acaaagaaaa ttccccatat accattaatt 189420
gtttactgta tatacttaga tatattgtag ataagaatgt gataagatcg ttggtggatc 189480
aacttccatc tctacctatc tttcgtcgct tatcatacta gtcatatcct aaatgttgat 189540
catattccac caaatgattg tgaaagagat tgagattaaa tcgtctaaca aacaattagt 189600
ttttatgaca ttaacatata ataaataaat taatcattat tgacttaacg atgacgaaag 189660
ttatcatcat cttaggattc ttgattatta atacaaattc attgtctatg aaatgtgaac 189720
aaggtgtctc atattataat tcacaagaat taaagtgttg taaactatgt aagccaggaa 189780
catattcaga tcatcgatgt gataaataca gcgataccat ttgtggacat tgtccgagtg 189840
acacattcac gtcaatatat aatcgttctc cttggtgtca tagttgtaga ggtccatgtg 189900
gtactaatcg agtagaggtc acaccttgta cacctaccac aaatagaatc tgtcattgtg 189960
actcgaatag ttattgtctc cttaaagctt ctgatggtaa ctgtgttaca tgtgctccta 190020
aaacaaaatg tggtcgtggg tatggaaaga aaggagaaga tgaaatgggt aataccattt 190080
gtaagaaatg tcggaagggt acttattcag atattgtatc tgactctgat caatgtaaac 190140
caatgacaag ataagactta ctcgcatcta ctggatagac ataaaatatc ctcctcgtaa 190200
taatgaaata taaatataca ctaattatta atatcaataa caatcgagta ttaatatata 190260
ggtcattttt aaatcccttt tgggttccgt cccaaacggc gtttcggtct gcgtcgccgc 190320
catggccatg ccgagcctct ccgcgtgctc ctccatcgag gacgacttca actatggcag 190380
ctcggtggcg tctgccagcg tgcacatacg aatggcattt ctaagaaaag tctacggtat 190440
cctttgtcta caatttcttt taacaacggc aacaactgca gtatttttat actttgactg 190500
catgcggaca tttatacaag ggagtcctgt tctaatattg gcatcaatgt tcggatctat 190560
aggcttgatt ttcgcattga ctttacacag acataaacat cccctgaatc tgtacctgct 190620
ttgtggattt acactgtcgg aatctctaac gctggcctct gttgttactt tctatgatgt 190680
gcatgtcgtt atgcaagctt tcatgctgac tactgcagcg tttcttgctc tgactacata 190740
tactctacaa tcaaagagag atttcagtaa acttggagca ggattgtttg ctgctttgtg 190800
gattttaatt ttgtcaggac tcttggggat atttgtgcaa aatgagacag tgaagctggt 190860
cctgtctgct tttggggccc ttgtattctg tggattcatt atctatgaca cgcactcact 190920
aatacataag ctctcgcctg aagagtatgt gttagcctct atcaatctct acttggatat 190980
catcaatctg ttcttgcatc tgttgcagct tttggaagta tctaataaga aataaagttt 191040
aaaatagaat taataaaaac atataggtca ttttttaaac atggattgga aaccaaggta 191100
gttagttaat acacacaaga tatatttttt tcacatcatc cacccatggg taacaccaag 191160
gttgttagtt aataatatac aagatatttt ttctcactct gatccatgta aaccaaggac 191220
gagataagac actctcattc ctcatccaca accccattaa aaaatggaaa ttaaagccct 191280
ctattagcat agacggctac aggtctacca tcaggttaac cttcgtctac cttcacaatg 191340
gcctttcctt gtgcccagtt cagaccctgt cattgccacg ctactaagga ctccctgaat 191400
accgtggccg acgtcagaca ttgtctgact gaatacatcc tgtgggtttc tcatagatgg 191460
acccatagag aaagcgcagg gtctctctac aggcttctca tctctttcag aactgatgca 191520
acggagctct ttggtggtga gttgaaggat tcacttccgt gggacaattg cgtggagatc 191580
attaaatgtt tcatcagaaa tgactccatg aaaaccgccg aagaacttcg tgcaatcatt 191640
ggactttgta ctcaatcagc tatcgtctct ggaagagtct tcaacgataa gtatatcgac 191700
atactactta tgctgcgaaa gattctgaac gagaacgact atctcaccct cttggatcat 191760
atccgcactg ctaaatacta aatctccttc atgctctctc actacacttt ttatcatctt 191820
atgaggaatg attgccttta tcatttttcg tgaaatagga ataattagca ccagaatagc 191880
tatggattat tgtggtagag agtgcactat tctatgtcgt ctactggatg aagatgtgac 191940
gtacaaaaaa ataaaactag aaattgaaac gtgtcacaac ttatcaaaac atatagatag 192000
acgaggaaac aatgcgctac attgttacgt ctccaataaa tgcgatacag acattaagat 192060
tgttcggctg ttactctctc gcggagtcga gagactttgt agaaacaacg aaggattaac 192120
tccgctagga gtatacagta agcatagata cgtaaaatct cagattgtgc atctactgat 192180
atccagctat tcaaattcct ctaacgaact caagtcgaat ataaatgatt tcgatctgta 192240
ttcggataat atcgacttac gtctgctaaa atacctaatt gtggataaac ggatacgtcc 192300
gtccaagaat acgaattatg caatcaatgg tctcggattg gtggatatat acgtaacgac 192360
gcctaatccg agaccagaag tattgctatg gcttcttaaa tcagaatgtt acagcaccgg 192420
ttacgtattt cgtacctgta tgtacgacag tgatatgtgt aagaactctc ttcattacta 192480
tatatcgtct catagagaat ctcaatctct atccaaggat gtaattaaat gtttgatcga 192540
taacaatgtt tccatccatg gcagagacga aggaggatct ttacccatcc aatactactg 192600
gtcttgctca accatagata tagagattgt taaattatta ttaataaagg atgtggacac 192660
gtgtagagta tacgacgtca gccctatatt agaggcgtat tatctaaaca agcgatttag 192720
agtaacccca tataatgtag acatggaaat cgttaatctt cttattgaga gacgtcatac 192780
tcttgtcgac gtaatgcgta gtattacttc gtacgattcc agagaatata accactacat 192840
catcgataac attctaaaga gatttagaca acaggatgta caagccatgt tgataaacta 192900
cttacattac ggcgatatgg taagtatacc tatcattcaa tgcatgttgg ataacggagc 192960
aaccatggat aagacgacgg acaacaacta tcctctacac gactactttg ttaataataa 193020
tctcgtcgat gtaaacgtcg taaggtttat cgtggaaaat atggacacgc ggctgtaaat 193080
cacgtatcga acaatggccg tctatgtatg tacggtctga tattatcgag atttaataat 193140
tgcgggtatc actgttatga aaccatacta atagatgtat ttgatatact aagcaagtac 193200
atggatgata tagatatgat cgataactct actatattac gcggtcgatg tcaataatat 193260
acaatttgca aagcggttat tggaatatgg agcgagtgtt acaacatcac gctcgataat 193320
caatacggcc atccagaaaa gcagttacca aagagaaaac aaaacgagga tagttgattt 193380
attacttagc taccatccca ctctagagac tatgattgac gcatttaata gagatatacg 193440
ctatctatat cctgaaccat tattcgcctg tatcagatac gccttaatca tagatgatga 193500
ttttccttct aaagtaaagt atgatatcgc cggtcgtcat aaggaactaa agcgctatag 193560
agcagacatt aatagaatga agaatgccta catatcaggc gtctccatgt ttgatatatt 193620
atttaaacaa agcaaacgcc acagactgag atacgcaaag aatccgacat caaatggtac 193680
aaaaaagaac taacgtccat cattacagaa actgtaaaga acaatgagag gatcgactcc 193740
atagtggaca acattaatac agacgataac ttgatttcga aattacccat ggagatactt 193800
tattactcca ttaaataatt tatcatggag cgataatgtc ctgtttcatt tgtttccatg 193860
acatattaca aaatcgattc cgtccaagat gataaaaaca tttaccggca tcataaacac 193920
ggagtttatt ttatatgtct cgcataaaca ttactaaaaa aatatattgt tctgtttttc 193980
tttcacatct ttaattatga aaaagtaaat cattatgaga tggacgagat tgtacgcatc 194040
gttcgcgaca gtatgtggta catacctaac gtatttatgg acgacggtaa gaatgaaggt 194100
cacgtttctg tcaacaatgt ctgtcatatg tatttcacgt tctttgatgt gaatacatcg 194160
tctcatctgt ttaagctagt tattaaacac tgcgatctga ataaacgagg taactctcca 194220
ttacattgct atacgatgaa tacacgattt aatccatctg tattaaagat attgttacac 194280
cacggcatgc gtaactttga tagcaaggat gaccactatc aatcgataac aagatctttg 194340
atatactaac ggacaccatt gatgacttta gtaaatcatc cgatctattg ctgtgttatc 194400
ttagatataa attcaatggg agcttaaact attacgttct gtacaaagga tccgacccta 194460
attgcgccga cgaggatgaa ctcacttctc ttcattacta ctgtaaacac atatccacgt 194520
tctacgaaag caattattac aagtcaagtc acactaagat gcgagccgag aagcgattca 194580
tctacgcgat aatagattat ggagcaaaca ttaacgcggt tacacactta ccttcaacag 194640
tataccaaac atagtcctcg tgtggtgtat gctcttttat ctcgaggata cgtaataatc 194700
ttgattgtac acccatcatg gaacgattgt gcaacaggtc atattctcat aatgttactc 194760
aattggcacg aacaaaagga agaaggacaa catctacttt atctattcat aaaacataat 194820
caaggataca ctctcaatat actacggtat ctattagata ggttcgacat tcagaaagac 194880
gaatactata ataccgcctt tcaaaattgt aacaacaatg ttgcctcata catcggatac 194940
gacatcaacc ttccgactaa agacggtatt cgacttggtg tttgaaaaca gaaacatcat 195000
atacaaggcg gatgttgtga atgacatcat ccaccacaga ctgaaagtat ctctacctat 195060
gattaaatcg ttgttctaca agatgtctct ccctacgacg attactacgt aaaaaagata 195120
ctagcctact gcctattaag ggacgagtca ttcgcggaac tacatagtaa attctgttta 195180
aacgaggact ataaaagtgt atttatgaaa aatatatcat tcgataagat agattccatc 195240
atcgtgacat aagtcgcctt aaagagattc gaatctccga caccgacctg tatacggtat 195300
cacagctatc ttaaagccat acattcagac agtcacattt catttcccat gtacgacgat 195360
ctcatagaac agtgccatct atcgatggag cgtaaaagta aactcgtcga caaagcactc 195420
aataaattag agtctaccat cggtcaatct agactatcgt atttgcctcc ggaaattatg 195480
cgcaatatca tctaaacagt atgttgtacg gaaagaacca ttacaaatat tatccatgat 195540
agaaagaaaa tatctatatg attggagaag taggaaacag gaacaagacg acgattacta 195600
cattattaaa tcatgaagtc cgtattatac tcgtatatat tgtttctctc atgtataata 195660
ataaacggaa gagatatagc accgcatgca ccatccgatg gaaagtgtaa agacaacgaa 195720
tacaaacgcc ataatttgtg tccgggaaca tacgcttcca gattatgcga tagcaagact 195780
aacacacaat gtacgccgtg tggttcgggt accttcacat ctcgcaataa tcatttaccc 195840
gcttgtctaa gttgtaacgg aagacgcgat cgtgtaacac gactcacaat agaatctgtg 195900
aatgctctcc cggatattat tgtcttctca aaggatcatc cggatgcaag gcatgtgttt 195960
cccaaacaaa atgtggaata ggatacggag tatccggaga cgtcatctgt tctccgtgtg 196020
gtctcggaac atattctcac accgtctctt ccgcagataa atgcgaaccc gtacccagta 196080
atacctttaa ctatatcgat gtggaaatta atctgtatcc agttaacgac acgtcgtgta 196140
ctcggacgac cactaccggt ctcagcgaat ccatctcaac gtcggaacta actattacta 196200
tgaatcataa agactgcgat cccgtctttc gtgatggata cttctccgtc cttaataagg 196260
tagcgacttc aggtttcttt acaggagaaa ggtgtgcact ctgaatttcg agattaaatg 196320
caataacaaa gattcttcct ccaaacagtt aacgaaagca aagaatgata ctatcatgcc 196380
gcattcggag acagtaactc tagtgggcga catctatata ctatatagta ataccaatac 196440
tcaagactac gaaactgata caatctctta tcatgtgggt aatgttctcg atgtcgatag 196500
ccatatgccc ggtagttgcg atatacataa actgatcact aattccaaac ccacccactt 196560
tttatagtaa gtttttcacc cataaataat aaatacaata attaatttct cgtaaaagta 196620
gaaaatatat tctaatttat tgcacggtaa ggaagtagaa tcataaagaa cagtactcaa 196680
tcaatagcaa ttatgaaaca atatatcgta ctggcatgca tgtgcctggc ggcagctgct 196740
atgcctgcca gtcttcagca atcatcctca tcctcctcct cgtgtacgga agaagaaaac 196800
aaacatcata tgggaatcga tgttattatc aaagtcacaa agcaagacca aacaccgacc 196860
aatgataaga tttgccaatc cgtaacggaa attacagagt ccgagtcaga tccagatccc 196920
gaggtggaat cagaagatga ttccacatca gtcgaggatg tagatcctcc taccacttat 196980
tactccatca tcggtggagg tctgagaatg aactttggat tcaccaaatg tcctcagatt 197040
aaatccatct cagaatccgc tgatggaaac acagtgaatg ctagattgtc cagcgtgtcc 197100
ccaggacaag gtaaggactc tcccgcgatc actcatgaag aagctcttgc tatgatcaaa 197160
gactgtgagg tgtctatcga catcagatgt agcgaagaag agaaagacag cgacatcaag 197220
acccatccag tactcgggtc taacatctct cataagaaag tgagttacga agatatcatc 197280
ggttcaacga tcgtcgatac aaaatgtgtc aagaatctag agtttagcgt tcgtatcgga 197340
gacatgtgca aggaatcatc tgaacttgag gtcaaggatg gattcaagta tgtcgacgga 197400
tcggcatctg aaggtgcaac cgatgatact tcactcatcg attcaacaaa actcaaagcg 197460
tgtgtctgaa tcgataactc tattcatctg aaattggatg agtagggtta atcgaacgat 197520
tcaggcacac cacgaattaa aaaagtgtac cggacactat attccggttt gcaaaacaaa 197580
aatgttctta actacattca caaaaagtta cctctcgcga cttcttcttt ttctgtctca 197640
atagtgtgat acgattatga cactattcct attcctattc ctattcctat ttcctttcag 197700
ggtatcacaa aaatattaaa cctctttctg atggtctcat aaaaaaagtt ttacaaaaat 197760
atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 197820
attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 197880
tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 197940
tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 198000
atggtctcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 198060
tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat ggtctcataa 198120
aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc ataaaaaaag 198180
ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa aaagttttac 198240
aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaaagtt ttacaaaaat 198300
atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 198360
attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 198420
tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 198480
tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 198540
atggtctcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 198600
tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat ggtctcataa 198660
aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc ataaaaaaag 198720
ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa aaagttttac 198780
aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaaagtt ttacaaaaat 198840
atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 198900
attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 198960
tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 199020
tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 199080
atggtatcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 199140
tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat ggtctcataa 199200
aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc ataaaaaaag 199260
ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa aaagttttac 199320
aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaaagtt ttacaaaaat 199380
atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 199440
attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 199500
tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 199560
tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 199620
atggtctcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 199680
tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat ggtctcataa 199740
aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc ataaaaaaag 199800
ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa aaagttttac 199860
aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaaagtt ttacaaaaat 199920
atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 199980
attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 200040
tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 200100
tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 200160
atggtctcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 200220
tcataaaaaa agttttacaa aaatattttt attttctttc tctctttgat ggtctcataa 200280
aaaatattaa acctctttct gatggtgtca ctaaaatatt tttattctca ttctcatttt 200340
ctctttctct cttcaatgga gtcataaaat atttttattc tctttctctc ttcgatggtc 200400
tcacaaaaat attaaacctc tttctgatgg tgtcactaaa atatttttat tctcattctc 200460
attttctctt tctctcttca atggagtcat aaaatatttt tattctcttt ctctcttcga 200520
tggtctcaca aaaatattaa acctctttct gatggagtcg taaaaaagtt ttatctcttt 200580
ctctcttcga tggtctcact aaaatatttt ttattctctt tctgatgcat caactatttc 200640
ttaaacaata acgtccaaca acatatactc gtcgagctta tcaacatccc ctatgcccat 200700
ctaggttacc agacaattgt atatcataaa ataatgttta taatttacac gttaaaatca 200760
tataataaaa cgtagatcgt ataatatttt ttggtatata aatgatctag taaaatccat 200820
gtaggggata ctgctcacat tttttctttg gtacaaaatt tcacacaagt ttttatacag 200880
acaaattctt gtccatatat tttaaaacat tgacttttgt actaagaaaa atatctagac 200940
taactatctc tttctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg 201000
atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa aaatattaaa 201060
cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa 201120
aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat 201180
ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc 201240
tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt 201300
tatctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt 201360
aaaaaagttt tatctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg 201420
atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa aaatattaaa 201480
cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa 201540
aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat 201600
ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc 201660
tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt 201720
tatctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt 201780
aaaaaagttt tatctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg 201840
atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa aaatattaaa 201900
cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa 201960
aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat 202020
ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc 202080
tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt 202140
tatctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt 202200
aaaaaagttt tatctctttc tccttcgatg gtctcacaaa aatattaaac ctctttctga 202260
tggagtcgta aaaaagtttt atctctttct ctcttcgatg gtctcacaaa aatattaaac 202320
ctctttctga tggagtcgta aaaaagtttt atctctttct ctcttcgatg gtctcacaaa 202380
aatattaaac ctctttctga tggtctctat aaagcgatcg atctttctta cactctagag 202440
tttcctacag tcatgggtca cacatttttt tctagacact aaataaaat 202489
<210> 22
<211> 908
<212> DNA
<213> Artificial Sequence
<220>
<223> polynucleotide comprising p7.5k promoter-DsReD
<400> 22
cctgcaggtc aattcggtag ttgcgatata cataaactga tcactaattc caaacccacc 60
cactttttat agtaagtttt tcacccataa ataataaata caataattaa tttctcgtaa 120
aagtagaaaa tatattctaa tttattgcac ggtaaggaag tagtcgaaac gaattcgccc 180
ttgcttgcaa gccaccatgg cctcctccga ggacgtcatc aaggagttca tgcgcttcaa 240
ggtgcgcatg gagggctccg tgaacggcca cgagttcgag atcgagggcg agggcgaggg 300
ccgcccctac gagggcaccc agaccgccaa gctgaaggtg accaagggcg gccccctgcc 360
cttcgcctgg gacatcctgt ccccccagtt ccagtacggc tccaaggtgt acgtgaagca 420
ccccgccgac atccccgact acaagaagct gtccttcccc gagggcttca agtgggagcg 480
cgtgatgaac ttcgaggacg gcggcgtggt gaccgtgacc caggactcct ccctgcagga 540
cggctccttc atctacaagg tgaagttcat cggcgtgaac ttcccctccg acggccccgt 600
aatgcagaag aagactatgg gctgggaggc ctccaccgag cgcctgtacc cccgcgacgg 660
cgtgctgaag ggcgagatcc acaaggccct gaagctgaag gacggcggcc actacctggt 720
ggagttcaag tccatctaca tggccaagaa gcccgtgcag ctgcccggct actactacgt 780
ggactccaag ctggacatca cctcccacaa cgaggactac accatcgtgg agcagtacga 840
gcgcgccgag ggccgccacc acctgttcct gtaggcgcgc ctataagggc gaattcgcgg 900
cctcgacg 908
<210> 23
<211> 2349
<212> DNA
<213> Artificial Sequence
<220>
<223> polynucleotide comprising mouse IL-12
<400> 23
accggtcgcc accatgtgcc ctcagaaact gaccatctca tggttcgcca ttgttctgtt 60
ggtcagtccc ctgatggcca tgtgggaact ggagaaagac gtctatgtgg tggaggtcga 120
ttggacccca gatgctcctg gagagactgt gaacctgacc tgtgatacac ctgaggagga 180
cgacattacg tggactagtg accagagaca tggggtgatt ggaagtggta agaccctgac 240
aatcacagtc aaagaattcc tggatgcagg gcagtatacg tgtcacaaag gcggcgaaac 300
gctctcccat tcccacttgc tccttcacaa gaaggagaat ggcatttggt ctacagagat 360
cctcaagaac tttaagaaca agacctttct gaagtgcgaa gcacccaact atagcggtag 420
gtttacttgc agttggctgg tacagcgaaa tatggacctc aaattcaaca tcaaaagctc 480
tagcagctct cccgattctc gtgccgtgac ctgtgggatg gcctctcttt ccgccgagaa 540
agtcaccctg gaccaaagag actacgagaa gtattcagtg agctgtcaag aagatgtgac 600
atgcccaaca gctgaggaaa cccttcccat cgaattggct ctggaagcta gacagcagaa 660
caagtacgaa aactactcca ctagcttctt catacgcgac atcatcaagc cagatcctcc 720
gaagaatctg cagatgaagc ccctgaagaa ctctcaggtc gaagttagct gggagtatcc 780
ggactcctgg tcaactccac actcctactt ttcactgaag ttcttcgtga ggatacagag 840
gaagaaggag aaaatgaaag agactgagga gggatgtaat cagaaaggag cctttctcgt 900
ggaaaagacc agtacagagg ttcaatgcaa aggcggcaat gtatgcgttc aagcgcagga 960
tcggtactac aatagcagct gttccaagtg ggcatgcgtg ccttgtcggg tacgctcatg 1020
atgcatctag ggcggccaat tccgcccctc tccctccccc ccccctaacg ttactggccg 1080
aagccgcttg gaataaggcc ggtgtgcgtt tgtctatatg tgattttcca ccatattgcc 1140
gtcttttggc aatgtgaggg cccggaaacc tggccctgtc ttcttgacga gcattcctag 1200
gggtctttcc cctctcgcca aaggaatgca aggtctgttg aatgtcgtga aggaagcagt 1260
tcctctggaa gcttcttgaa gacaaacaac gtctgtagcg accctttgca ggcagcggaa 1320
ccccccacct ggcgacaggt gcctctgcgg ccaaaagcca cgtgtataag atacacctgc 1380
aaaggcggca caaccccagt gccacgttgt gagttggata gttgtggaaa gagtcaaatg 1440
gctctcctca agcgtattca acaaggggct gaaggatgcc cagaaggtac cccattgtat 1500
gggatctgat ctggggcctc ggtgcacatg ctttacatgt gtttagtcga ggttaaaaaa 1560
acgtctaggc cccccgaacc acggggacgt ggttttcctt tgaaaaacac gatgataagc 1620
ttgccaatgg tgtcagtccc taccgcttct cctagtgcct catccagcag ctctcagtgt 1680
cgtagcagca tgtgccaatc acggtacctg ttgttccttg ctactctcgc tctgctcaac 1740
cacctgtctt tggcacgcgt gattccggtt tccggtcctg cgagatgcct gtcacagtcc 1800
cggaatctgc tgaaaaccac cgatgacatg gtcaagacag ccagagagaa gctgaagcac 1860
tacagttgca ctgcagagga tatagaccac gaagatatca cgcgagatca aaccagcaca 1920
ctgaaaacat gcttgccact cgagttgcat aagaacgagt cttgtcttgc cactagagaa 1980
acctctagca ccacaagggg cagttgtctc ccaccccaga aaacgtccct gatgatgaca 2040
ctgtgtcttg gaagcatcta tgaggacctg aagatgtacc agacagagtt tcaggccata 2100
aatgccgctc tgcagaacca caaccatcag cagattatcc tggacaaagg gatgcttgtc 2160
gccattgacg agctgatgca aagcctgaat cacaacggcg aaactctgcg acagaaacca 2220
cccgtaggag aagcagaccc ctatagggtg aagatgaagc tctgcatcct cctccatgca 2280
ttctccacta gggtggtgac catcaatcgc gttatggggt atctgagttc cgcttgagct 2340
agcgaattc 2349

Claims (33)

1.一种牛痘病毒，其包含下述(1)和(2)：
(1)编码白细胞介素-7(IL-7)的多核苷酸；和
(2)编码白细胞介素-12(IL-12)的多核苷酸。
2.一种药物组合物，其选自下述(1)或(2)：
(1)用于与含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物组合使用的、含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物；或者
(2)用于与含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物组合使用的、含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物。
3.一种组合试剂盒，其含有下述(1)和(2)的牛痘病毒：
(1)包含编码IL-7的多核苷酸的牛痘病毒；和
(2)包含编码IL-12的多核苷酸的牛痘病毒。
4.如权利要求1所述的牛痘病毒，其牛痘病毒生长因子(VGF)的功能发生了缺陷。
5.如权利要求1所述的牛痘病毒，其O1L的功能发生了缺陷。
6.如权利要求1所述的牛痘病毒，其VGF和O1L的功能发生了缺陷。
7.如权利要求1所述的牛痘病毒，其缺失B5R胞外区的SCR(短共有重复序列)结构域。
8.如权利要求1所述的牛痘病毒，其VGF和O1L的功能发生了缺陷，并且缺失B5R胞外区的SCR结构域。
9.如权利要求1和4～8中任一项所述的牛痘病毒，其为LC16mO株。
10.一种药物组合物，其包含权利要求1和4～9中任一项所述的牛痘病毒和药学上可接受的赋形剂。
11.如权利要求2所述的药物组合物或权利要求3所述的试剂盒，其中，牛痘病毒的VGF的功能发生了缺陷。
12.如权利要求2所述的药物组合物或权利要求3所述的试剂盒，其中，牛痘病毒的O1L的功能发生了缺陷。
13.如权利要求2所述的药物组合物或权利要求3所述的试剂盒，其中，牛痘病毒的VGF和O1L的功能发生了缺陷。
14.如权利要求2所述的药物组合物或权利要求3所述的试剂盒，其中，牛痘病毒缺失B5R胞外区的SCR结构域。
15.如权利要求2所述的药物组合物或权利要求3所述的试剂盒，其中，牛痘病毒的VGF和O1L的功能发生了缺陷，并且缺失B5R胞外区的SCR结构域。
16.如权利要求2和11～15中任一项所述的药物组合物或权利要求3和11～15中任一项所述的试剂盒，其中，牛痘病毒为LC16mO株。
17.如权利要求2和11～16中任一项所述的药物组合物或权利要求3和11～16中任一项所述的试剂盒，其中，包含药学上可接受的赋形剂。
18.如权利要求10～17中任一项所述的药物组合物或试剂盒，其用于癌症的预防或治疗。
19.如权利要求18所述的药物组合物或试剂盒，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
20.一种预防或治疗癌症的方法，其包括对需要癌症的预防或治疗的对象施用权利要求1和4～9中任一项所述的牛痘病毒的步骤。
21.如权利要求20所述的方法，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
22.如权利要求1和4～9中任一项所述的牛痘病毒，其用于在癌症的预防或治疗中使用。
23.如权利要求22所述的牛痘病毒，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
24.权利要求1和4～9中任一项所述的牛痘病毒在制造癌症的预防或治疗用药物组合物中的应用。
25.如权利要求24所述的应用，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
26.一种预防或治疗癌症的方法，其包括：对需要癌症的预防或治疗的对象施用(1)包含编码IL-7的多核苷酸的牛痘病毒和(2)包含编码IL-12的多核苷酸的牛痘病毒的步骤。
27.如权利要求26所述的方法，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
28.一种牛痘病毒，其选自下述(1)或(2)：
(1)用于与含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物组合使用而在癌症的预防或治疗中使用的、包含编码IL-7的多核苷酸的牛痘病毒；或者
(2)用于与含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物组合使用而在癌症的预防或治疗中使用的、包含编码IL-12的多核苷酸的牛痘病毒。
29.如权利要求28所述的牛痘病毒，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
30.一种牛痘病毒的应用，其选自下述(1)或(2)：
(1)包含编码IL-7的多核苷酸的牛痘病毒在制造与含有包含编码IL-12的多核苷酸的牛痘病毒的药物组合物组合使用的癌症的预防或治疗用药物组合物中的应用；或者
(2)包含编码IL-12的多核苷酸的牛痘病毒在制造与含有包含编码IL-7的多核苷酸的牛痘病毒的药物组合物组合使用的癌症的预防或治疗用药物组合物中的应用。
31.如权利要求30所述的应用，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
32.(1)包含编码IL-7的多核苷酸的牛痘病毒和(2)包含编码IL-12的多核苷酸的牛痘病毒在制造用于癌症的预防或治疗的组合试剂盒中的应用。
33.如权利要求32所述的应用，其中，癌症为恶性黑色素瘤、肺腺癌、肺癌、小细胞肺癌、肺鳞癌、肾癌、膀胱癌、头颈癌、乳腺癌、食道癌、胶质母细胞瘤、神经母细胞瘤、骨髓瘤、卵巢癌、大肠癌、胰腺癌、前列腺癌、肝细胞癌、间皮瘤、宫颈癌或胃癌。
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