rojjer 发表于 2016-1-5 17:18:57

最新综述:乙肝病毒生物学及新型抗病毒策略研究现状及...

乙型肝炎病毒(Hepatitis B Virus, HBV)是一种具有独特复制模式的嗜肝DNA病毒,可导致急、慢性乙型肝炎,并与肝硬化、肝细胞癌等肝脏疾病的发生相关。当前临床上治疗慢乙肝的药物主要包括核苷类药物及?干扰素两大类,其主要起到抑制HBV复制以减轻或延缓HBV慢性感染所导致的肝脏免疫病理损伤、降低相关肝脏疾病发生风险的作用,但无法根治HBV慢性感染,且存在需终身治疗、耐药性和副作用大等局限性。
data:image/png;base64,/9j/4AAQSkZJRgABAQEAYABgAAD/2wBDAAYEBAQFBAYFBQYJBgUGCQsIBgYICwwKCgsKCgwQDAwMDAwMEAwODxAPDgwTExQUExMcGxsbHCAgICAgICAgICD/2wBDAQcHBw0MDRgQEBgaFREVGiAgICAgICAgICAgICAgICAgICAgICAgICAgICAgICAgICAgICAgICAgICAgICAgICD/wAARCAFrAfQDAREAAhEBAxEB/8QAHAAAAQUBAQEAAAAAAAAAAAAAAAECAwQFBgcI/8QAVhAAAgEDAgQDBAcDBwgGCAYDAQIDAAQRBRIGEyExIkFRFDJhcQcVI0JSgZEzYqEWJENygpKxNFNUY6KywdFEdYOTs9IXJSY3VWRzwidlhJSj8LTD8f/EABoBAQEBAQEBAQAAAAAAAAAAAAABAgMEBQb/xAA0EQEAAgEDAgQEBAYCAwEAAAAAARECAxIhBDETQVFhFCIycQWRofBCUmKBscEV0SPh8YL/2gAMAwEAAhEDEQA/APqmgKAoCgKAoCgKAoCgKAoCgKAoEZ0X3iB86CrNqthFbTXHPjdIULvtYHoKNxp5XVK/DWsvrWh2mqPatZm6Xf7NIQzL1I6keuM1Im11cNmUx6NOq5mySxxIXkcIg7sxwP1NBjzcZ8LQyGNtThZx92M8w/7G6rSWhHHnDBbb7TIMeZgnA/XZilFrVpxZw1dycqDUoGl/zZcK36Ng0otrd6iigKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKAoCgKDjON+IHeFtI0tZZ71nVJDbnBXrlk+e2s5Pf0mhzuy4j3eX6rx1bTXjmW4u9Sj9mZZIYoZQ0M0RxHAzbcKz9dzY6Vm308NKo4iI5VxxlwmicmOLUI4YhIUd1bGIQHhTaUG7muSOvbFZuWtup7Nzh36UFsZJkhvlubODkbIJMJk3HidUX3iUY7OnnWoycNXpIz8ql6kuq32s6YraLLFa3ZZRce0DmGFSM9FUgFvTJxXR8bV0pwmkMXA2lSye0avLNrNz+K8bdED+5AuIl/u1bcqbtvZWdugS3gjhRfdWNQoH5CoqagqXuk6XfRmO9tIbhD92RFb/Ggxf5Iz6cTJw5qEth5+wzE3Fmfhsc7k/sMKtpR8HFb2l1HY8RW31ZczHbb3QO+zmb0WXpsY/hfH50ot0VRRQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFBS1XV7HSrZbm9flwNLHDzD0AaVtqlicADJ71BhyfSNw4t17OjtN9oYubHtZS2/l+DxZfLfhzVGrYcQ2F/NDFbli80HtOCPdTfs8XodwIx8Kgg4s1iXS9CuLmHBuD4IV9Wb0+IFLejptLfnET2eYcW3jaHokUUNk1zq/ER5cm55OZh/cVZY/dlzhviK88zc+0PqYfPl3+XBuaFYHh7RILIuZ7pjuuZc+Ka4YZd2Y+nqfKvnZ5znPs45zvytOJ9YkTnRxq0OOwiLKfkxIJ/JazsWsXLcdRe06Ims2cPs+r6IfaVaFVEjW7+Cblkr3x2yOhrv0+pzU+btpRU15S0+D9ct4H03W7ON0sNV+ynUO7pG6DDg5A3nz3AYzmvoYT5Ma+E54zjPfF6S3EFrzWiiguZmTvy4Hx+TEAV1fFQycQ3Ybw6Tc7P8AOSmGJf8AaegifiuNB4vZUbzR7yIH+G6gqPxhKxxE9gPnPJJ/uR0CHiHWmHgnsB/VS5k/4LRFG+1PWLuB7e5urWSCQbZIm066lUj4gmljDXVOKuHURLa+N3ou4mYyadclrJMd0y2XiHnk5FWxrWXF2rXfMaz1W3vEiIEhj0+5IBZdwyVdvI5qC+nE2uj3hA/ztryP/wC1hQW04qvEH84t4R8RJIn8GjoGycc2sf8ARK58ws8YP/8AJsoLNrxhYTrnkTA+i8uX/wANmoq3HxHpbAlmkix35sUif4rQOi4h0OQ4W/g3fhZ1U/o2DSi19HV1DIwZT2I6igdQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUCZAGTQQDULAllFzESmdwDrkbe+flRrZKhwxxCuvafJfJbPbRLPJDGJMZdY2wJOnYN3FSJtvW0pwmpa9VyFAUBQFAUBQFAUBQFAUBQJmoEzRVHVNMtNTgSC6GYkljn29MFom3KDnIIyOtBhXX0f6I1zJcmaSCGRzLPEOWE/aCXoSuUww+6RQS2P8ltDub66gut8mpTcx0UmbafwRqgJC7iWx6k0pLctxXxUmsS2lnBDc6eYLnxPdDkmQe7hU6nxZ6ZrFvrdHpVEzxPDn7aCLW/pK1e9aaGb6pi5Wnyxo0ZLN4fED7xg6rvFePqJrD7u17dKPd0V3Z3imbmT8zdbqIBgAKA684/3e/wAK82EMY5R+v/x1llZXqRMbuZZ9wXlMnbHw/wCfnXpnF4cso8uHP3i2s+rAB+ar8yGRPuhdmJB6HJP61483qxva4TQPbbbR9c0Z5X5eiXqxw38lxkICcRxJDjKJy28TetfUxntPq9fE5xP80dnp+g6hZ63HHzbW6jlCdZS8ohbaMZVgw7+XSuu58nX6fZPdotwtw4775dOgmf8AFKvMP+3mm6Xn2wuQ6ZpkIxDZwR/1Y0H/AArNlLA2qPCAPkMUUu40UbmqCG8t1u7WW2ld1jmUqzRsUcA/hYdRVSnmVrow+ifTNbubfUOdpuosr2BuYpJTDcgHwzGL7jjoG9a6ZZbnTpun3ZUjGi/SjqVuNXu+IrfSPbHW9FhtkIgzHyxFncOm1skfirhlqxD37tKPljGZrhVtNG4vh28vjaFn5sDFpIJtpNquxV37uoYe/wDirHxGLpO3+T9yuaHrvEHDXENlw1xNcx6pY3aPJp99HCZHuGkbc3MkdtqJD1J+FdscrctXRw1MZzxipjv+/d6HPoGgXXil0+1l8w3KT9QcUuXzdsFXQdLRdkUbQr5COSRAPyDAVdxtVJ+FLSXP87ucH7shSZf0kVqu5NqvDwgLVW9kmiQn0i5X68lkpuTaiGmcV22WSYynyWC5Yf7Nwrj/AGq1uSk0mqcS20XiWXf+KW2EqD5m3bd/s0sOtOMrhsCWCCUDpI0U3KK/9nOsbfxqjRHFWnKN1zHcWqHoJJIiU/vx8xP40Ghb6lp9wQILmOQnsqsM/p3oLNAUBQFAUBQFAUBQFAUBQFAUBQctxpxF7LZT6fY75dUlUKqwnxJvPTPnk+VSXs6TQ3Tc/S801HjKyF1b2uoapPNHHHPFPaRh3lgaNMjnYHvu42rXPc+ljpVHyxH3ZtrxXwFIkdtJ9YWo3DdI5zt3xcx2Y7Rkbxy8HzrN5Os+Ld8Njh76Soo5pPqy+D2sdsl49nPsiKNK21oyM9SmOu31rcZOOp0sZfVFTdW9Y0DiK01m1EkQMcuAzQtjcAezfI10fI1tGdOWtRxFAUBQFAUBQFAUBQFA3PpUFG91rS7JxHc3CrO/uQL45Wx+GNcsf0q0WydQ4wjglWGK2PNddyidtjflEm+U/wB2lFq81xxZeuFiV4Ld1/o1WAj/ALSbe36JThCycLX10Y2u5ofD7/MD3bH5cwrGPySm5aX4OG7GKIxyz3Fyvo0mwY9NsIjGKzZTD410W0tNGjurK0VUtJhNOiEISAPCxY9TtNSZe7oOMq7XDieL9Uj0jjDR+Jwz+w6lGLe43y9ApGHEcG3wCNvEzE9a82enuxmHt0sLwnDzhJq1xxhHx5bctLhtEhMUkbQgNBysfbF/MsfIV86JmHfSjR8Cb+t008N5c22yBWs7d23xxc5gAM5G6PBx8ga6zqPHExE88z9mfxFrFvwzol1q9w6yXJAit+yoZW/Zoo8l3eJj+dZwx35U3hjvnb5MDROH5rLh63N1bLcaxrk3MuyyCKblO27Ekis6uvM6ofSvp49/aHbxLynmoxjh7RCnKgih8o1Vf0GK0+JPMn1AUCUDTLEJBEZFEpGRHkbseu3vVDuvpRSZqDyTXZX4m+k+OxuC0WkaKBJdhhtVxnMaFlcpJHIw3ZIyMVM8qh9PSjZpX55NrVdUXUbguJcWsUohDkeFW7vJjsdo93y86+ZlMzK6ent+65b6Tpt1bG4tJHfPhW6VySencHsf0xTY55auUTU/k5XjjQV1fRLmxhBF7pub3TvDnxw4M6qp6bJEOcds136bUqad9LOpvynif9O/4H1ldV4asbjL7xEo+2aIzMuPDI6xdE39wte587Xw25S381HEZNAZNAu6qDcagbKkEwxKiyA/iAP+NVKURw9o6MXt4fZnPc27vF/BCBVtNqjc8LyvtxdJdoDnZfQpI39mWPlsKu5naha11u0eMRJcQxqejWc4nj/tQ3PXHwUiruSkkPE99A6208tvPc52iOcPYyv8FEm6Nj8mrQ1BxLbRRq+oQTWOe7yLuiH/AGke5cfE0GnbXdrdQrNbSpNC4yskbBlI+YoJaAoCgKAoCgKAoCgKChrmpfVuk3V6MF4UJjVuzP8AdHT1NHTSw35RDyrWtXTRuHH4ivbaS41XVvsLcFpNygjBAlTPLc5+zz8q8+U3NPrxjuy8OPphb4S0uXRdE5+pSNcarfMst9PJ45ncjEUWT1YquFr5+tqbp47Mak7suO0NET3cySMlqrKuQQEMg+ILDAOPPGa57JSohznF+m22r8PyzWlvHb61peL+xlVFJzF7+MjxDHTDDoa7aOrOOVT2l10/ly/pngvC/EUJtLLifTtzszLa6mhk3NzD13y7AF3OnUqvavo4TU0upp7r08vvD2eGVJYkljOY3AZT8DXV8KYPoCgKAoCgKAoCga7qilmOAoyfkKg5++4rCEJb25BfpFNdExK3oUjG6Vx8lq0lqPI4m1SDxM6buvMlzaw/lChMzD+s4qi9acJWcSrzpncjO5YsQIc+R2eIj5tU3LtalrY2Nmu21t44fLKKAf171m1pOTUUneoEoGTwxXEEkEyhopVKup9DRcZrl5Vxjos1jpl9pF4kl7YXTK1gzsyrvPhXmyRjdt3d086kw+xo5+JWUVEx3UdL4j43sEi0aXRY9XaykhshfQTFeaZE3IfEv3VHiPl515dTp8Z9jPTwn5rq+UkH0iajKy44TvismzYeYvXmyGFO4Hd1Nc/hPdJ0I/mhnvqFzxDr1rq99YXFjpOnLILO13Qzb50YpKLiJgfBLjlqfKvRp6W2HSMNuNRNzP74ehcLaLNc3v15exPbHaqWtmRsRAoxjl+i/drt2ePqNWo2R+brqPCTcKikzQQ3V5a2sYkupkgjztDSMFGT5ZPnQchdcN61c3F/PpkVnK9/Mbqx4gaQtLCDFsEaBQTkHopDbcHtmtMqcvC/GlxHc+zam1vIFTkWQujMyKJPt42kwPE4HRvu9qg7DhlbgaBZc66F/MseHu1OQ7DI97z9CaivOfo4gs7TWeJdAvLe3i1B7kXwFtv9nIHRoozIFLCIt18utc9aOH1OomZxxyi6ql/n6XDr0mkQSRNdh1uVtCfvqPHG/puXqtfOxmpb25Thvnt2t0N7xBYWNjuWxnTr4oVTbg/1vcx09a75akU8uGhOWXeGVb6hHbLea/fMGs9PhlPM7Kd3dUz5YAXPma56MXk654/wx3lX+hHTprXhy7uWihijv7qS4CiKSK4RmJLRTb8bgmRsI6Yr6cufX5Xl9oeiZFZeIuaA6UB0oExVBigMUB/w8qBk91BbwPPcOsUMSl5JGOFVR3JotD+aXtujER3NvIA8e4B1IPUEZqszCiOH7OJy9nJLZMc5WFzyzn1jbch/SruTazZtC1CGRpBFFcj7k9oxsboeucfZN/CtRkzRya7f20qA3ICkkNaaons8nT8E6ZQ/mK1aNdOJLZOmoQyWB6eOQboTn8MqZU0GrFLFLGJInEkbdVdTkH5EUDqAoCgKAoCgKDznjjil7u3n0z2G608w3IRNQuRy4WKddyEbtynyrO59PotDndxPHZyF1HFrn0k2tnJNDNaaNZrOoiLhmcAbYZhnY7Rud+QK8mtNYT7vVHy6cz6y6mWHUFwXl3uLWU24x/TY8R88kITivFpw5RMfq6DRLPU0tUF48LQCMez8kEeHpjOfPv2r07eHl1csb4tmapyBqkBDguJQnKH7ynmZ+a9TXl1IdtO9rg9Ein0x+KeHvt2ttPYXlrKJEW3t0mbmR4TG8sxY7j6V9DTm6l67uccvXj7vT+C+IfaLG2sfZpn5S8v2xQWgbHnvNeqJfM6rQqZn9PN1lV4xQFAUBQFAVA0tQJRVK00rT7SV5oYR7RISZJ28cpyc++2Tj4UspbzUU3NQJmgSoCiigKgo6zpkWqadJYyuUSTB3r3BU5HejppamzK4YEnAFsk3OsL2a2lKhJGJ3565LA9MMatvV8ZPaYiVU8EcTyLypNdJVSzBhu3Od2UV+uMfKpUN/F6f8hvAWkaVeWUmq3Now1AXE0MiTAqAYn29E7EeYNSJTqdfL6Yn5adsXo8JKAxQFQZHEehyauNOVJzbizvEundff2qjrhchhnx+Yqo5i6+jjU/rRPq+/wDZdHjXlmESzc143H2isQcDLktkYq2UI/o91a1uZjaXEXsBuZJo7JpbhFIdmZWdlO7dGWHTPXFLKP4W4C17RtXtrq51QT20EZQxIzgYKnMYjPh27jvz3zS1Zn0nafqmla5pvGGlrLcT2z7ZoV5kh5YHjjVR9nHGVyzsepNPZ9DpMoyxnCfM6y4Ct7zWv5V6Rq49hv29vtbZlDbZplwdzZyV69q+fn0/NvRP4hPh+Flj24dDDwtaqQZsTSY+0aRydx8yVJx/CseDLyT1EuU4/R9f1Wz4HsDJ7Lujn1m5t4+csef2Ecyhl+yJHir26OntddCdkTqT38npmmWEGnadbWEHSG1jEaDJboPixJ/Wur5+WVzazmoyMigOlAUUURj8TwalJb2EtjA1zJa3sNxJAjqjNGmdwBYgefaqKOo6ZxVfavDdLPHaWi29wsaoMyKZlXakoLFScg9Vqo5ez4Q4ztJnuLVWgvUEv85EkZ3hokVQCWJcgqcBgAKWNS61TWrzQrjhue0kuNeihi+tF6ODb3DMMqRgMwUeIeVR6+nwiJjLLiP9uk4UW+j0SCC8hMMlt9jEjdG5SdEJHl0o56+3dw1wTRxZXEeq6np1tby2NmbrmS7J8Aty0x72F696rtoaeOUzc1wp2/FNpNBaWmsW3Kur3cGtnUMiruwpkDe6HHbNG8+m77eYhfOgRQn/ANWzvYgnLQr9pA3TGDE+QB/VxV3PHtZclneaazTezvagEE3eleKPA6ky2beXrsBNbjJmYaNpxHdiNpZETULRepubHrIo/wBZbnxjHwz8qo2bLUbG+i5lpMsq+eO4+a9x+dBZoCgKAoMTiLi7RdEgf2i6iN7g+z2W7MsrY6KqLufr8qtJMuSPEGocc8F3V99STWFpG6vHHcugadYz9ptzjao9TUyh6uh1K1PRyvFmpyWUugcWw7zaRBbe7TfGkSA+F0VMCSSRx4s9sCvLlhcTD6mnhzlh5pOM7zi1Ne0j6nWdtOISaOS3GY+ZuyTP38HLNfMi4dukjR2Zb/qdTM19cWrjTJJ7O2frDtkVQeuSQrqWQE+QNdvEeKKifmqZVb67t9E0251nVJQwtIiWK9sn593kbGTXKI35VCx807Ycfw/pk31Nd8Q31tzdZ1ufaVZXimETY5ibtxR4cbdjV9TGPLyh6t3z7Y+nGP3/AHe4aDZNY6PZ2jDa0UYBQdgfT8q9D4WrnuymV+jmKAoCgKAoGk1A2ikqKQmoENAneoEoCqorISgKikoEJqqTNQHWgMCoDNAuDQQSXllE2yS5iRh1Ks6g/oTQUH4p4cW49mOowGfGeWrbjj8s1S1qDVLGcExy9F6eIFf03YzULMu9WsLWPmSyFlzj7NWkP6KCaFqf8q9G9bgf/ppv/LVSzbzVOHtSsZrO73y2lwuyaJ4ZgGX0PhBo1jlU3Hdwl1wF9GSagZvrH2KCe6ikjscyRRhVUq0C9RgSOdxq29fx2dF0/wCiDhd9TntTqFzPPYezG5RmcKwZmkODv/pUwh9MUtr/AJDKfR13CX0e8P8ADQEtnCJdQzKDqDD7Yxyvu5bHJyFGAPlUtx1uoy1O/b0dLUecZoCgM0BmgXNAvWgM0CjHn2oOS03QdTh4rlu5NRikk3tLPGCeb7NJkRxsO2Mj+FV7M+ownDbXl+5U9A1hLjj2+uRDMhvx7HynzhPZM+MjsN1Kb1tCtKPbn83dVHgc7rOhcR3WpSXFjqvs1q6Iqwnd4Cp8TDHQ5q29WlracY1ONyfrXDejSyzatcwT3NzsjEyQMd0gi93wdiarGPU5441HY/8AlvoCDN21xY+QFzbzR/x2kfxq7Xl3HpxvwexAGs2qk9g0gU/7WKbZXdCC71Lgi8ZbhtUs0nXJS6huUjlGf3lPX86sWzwxL7X+HYHE0+rWmoPH+zvLWZIL9Q3rs8EuB/8A8rcMrenfSTp4aKBLk62HAObWCQXagnvLAFxjyyv6VaLa9rxsmoRs2k6Xe3u1mRiUWAKy9Crc1lIP5Uos2/1fiqO2a6mjsNFs0AMk95K0zL/Zj2Ln0G6gwm0jijiRdq6peRWL+/fyqLVWT/UWseGOfxSt+VVHScMcCcNcOKW0+1zdv+2v5jzbiQ/vSN1/IdKkysQ3THHy+XtHLI27PLHpioryzjDQJtItr+GYT3mhXaZSJGCsjdfAJQMxrjpnzFYnF9jp9WNSu0ZwwNH4s1zQtNXSNQ0ltRNgkGy6tpc/Z3L7IIzuAJZT4f415dXp4yn0dM9LHKbiatam+k1YHIn4e1BQGkVmBRusMgik/uuwFcfg/dI6f+qFDWdTuuJdXsbeWzu9I0nS53N1zEimJu4uuJoS3iiUdPma76Wjtaww2xPaZn/Du+F9CfU76DU7m1aysLOPl2diBy4wAcqoT7yedenHGnl6jV2Y7I5mfN39bfMFAUBQFAVA0nNFNJoEqKSoGk0CVAUBRRUCUUlQBIoppJNAAGggur+xtP8AKZ0h9A7AH9O9QZ0vFNlhTawT3QYEiQLyovzeXaOvlVRlPxlOSmTawZfBiVnupMfh+zAAb9aFtY6rdH3VCg1Etz9xY6rc3FzI6Q4lY7WlnnkBHxiXaq/IGqlm2ugTQRbA1pH0xtitVIHyMhZqCxFpF+pbfqlw0Z7RKscar8tq1BatYI16LO0/M93e4f3e+3/jQPudPFxHy2MijPeNih/UUFX6gtl6iS5UevPk/wCJoEj0RDiSK8uyh7YmJX/CgkbTJwfBe3KeoLBv4EUGfEnJ41nUZHtunI5/rW8pX/B615M+Z1xo989xPKnIKynPR54ZT/WdGI/QVlpGs3E9tCQRdpy+u63njusj8KrKEY0LWRxZqMLx82SPDj9ndQSW7bvIb03J86LbZ0jiGO+hZpo1gZTtzHKs0bf1WXr+oottP2m3wDzVAPQZIHWoqXrQJmqCil60QZoMS1P/ALbal/1fa/8AiPWvJjzbvSstloDNAuM9qA8fxqiNrW3f9pBG/wDWRT/iKqUh+qdIP/Qbb/uY/wDlV3Sm2EyWdnH+zt4k/qxoP+FSykd7pdnfAc1SsyfsriI8uVP6rr1/KrEpMON1nVL631B7bS421jVIsB760+ze3x/ppH2ci/ujxfCukMSs6WI2vF1LiSZdYKNm2v4h/M7Y/hNt1ML/AL7Z+Yqo7uOSOVFkjYPGwyrqcgj4Go0dQFBW1GxivrGezlyI51KMR36/OjWGW2b9HLy/RvZIElsryaG8RNnNc7wx9SOmMfCpT2x189piKU2+j/iF1kgbXCYWYkSbTzMEe7j3e461nY6fG6ffbyi4N4Zsbu91GbVIGbULC6Nu2dyxuAoO4Ds4bOaQnUdVMREY9ph6CqqqhVGFHQAVt80tAUBQFAUDSaBpNRSVFJUDaAqBKKKlgoEqKSik3UENzc21rEZrmVIYl7ySEKP40FCHiKxmkIjjl5QHhmZNiufRQ2GPzxRLQajf3FxbvHCjr6cuQxuceW4dqiWwLbSNQAGGgsve/Ypzpuv+tlz1/KiLUXD1gGWS45l7MucS3MjSd+/h6IM/KgtI2n29xHYo0UNxIpaK3XCsyr3IXzxShZUIzEAgkdwDRT+X8KBdlAoUZoOL/khr7x2Vpzo4LaweT7eKR1kmimuBI69MbPs+nfvWgn8lOLlG03zXAHLBc3UqF4Exut8D3S2P2veggfg3jKZ9t1fi4twgUx86Qbgu1lUn1Ug9aB9xwxxNZ2ouoruaeWMye0WkMr/aQNjbEi9MHOeo60G/wda6pBw3aR6qrpfZlZ45HMjqrys0as56nahAqSE1QcnijQph05y3Vq/x3IHX+KVY7JPds7KypOWKBpj8qIiFtFHu2Rqu7q20YyfyoKuoWMtxGqxvGm05IljEit8PIj5igzIk13S8eyiaOIbsJbP7RDjvkwT+L+61BpWHGbyNsmhW4Ixu9nykyg+b28u1u/pRq27Yatpt/n2WcM6+/C3glXP4kbDCirlQQXsV7LblLO4FrPkYmaMSgDzG0kVYGJHw7xGmozaiuuL7TPEkL/zNNu2Mkjpu/erW6GdrftluEgjS4lE86j7SYLsDH12jOKjSUGoF70HnnGHGOtX2sycH8KSRDUZ0eG7uH5sU9kw6mbtgpt90jzqvbo6GMY78+3+Wbf6L9KkUhmueKLG3R3UspMgXPJ5GAPQ+/gferHi4uuM6U9sZMh0T6TrhWtrXiqykkSK1jVQZVf8Amp3BsHrmbtIfOrGriszpRzOM+f7/ALOn+j/ju84gkvrHVbdbXWLKRhcWsKScqIKduxpX6M7e9geVbebqOnjCpjnGXX3V3a2ltJdXUqwW8I3SyucKo+Jo8kue36zxMPsTNo+gP/Te5e3S/uecEZ9fePwrXZju39P0+w061S0sIEt7ZPdjQY/M+ZPxNZapXvdFhnm9qtnNlf8A+kxD3x+GVD4ZF+dWMkmGMr32kXXTZYvMSFjOfq6dj16HvbyH9DXSJZdFp2tQXcrW0im2v0G57STG7b+JCOjr8RQaNAUBQFAUBQFAUBQFAUDCayptFJUDSaAqBKKKgSgSooJxRVS+1GysoxJdzCJT0Ud2Y+iqOpqjndS4suM7IP5irjwcxebdv/8ATgGQvzeozbOWz1S8k55X2Yn/AKTd/wA4uuv4E/Zx0tFr2KysHW4fm3V8+ViaRi8rE9wvko9fSpMtY4WHkmEuyed2n87KyXOzPbc/r+lZd4xjyjj1krO8J6zXVrjrzZ1EsR+DY7UIxvyifsv2l0zv7PcKI7nG5dhzHIv44z/w8qsOeWHnHZa5S7g20bx2bHUfI1phWg0bS7a9kvYLVIrqbPNmXoWz3z5UtKJY6RDZ3Es8dxcSc7OYpZS6Ak5yoParZEFsLXVoDN7VfC9Vv8nDQrEyH0LIfEPyoEsH1zlTHU7WBJE/Y+yymQSf3wpU/OkkCz1NprWa4uLK4seR+0jnUFiAM5XYW3ClFnWesaXeWkl5BcD2aI4klkBiCn97eFxSltbhkhnQSQSJNGezxsGH6jNQP2MPKgTafSgxeJwYxpN2B1t9QiGfhLmM/wCNXFJbJXqaik20CbaBpSoE2UQwx0Rn6umkLb87VTCkC9pZiF6/ut3z8qQMC1vJDeLNolnd6jHGPsZLnbFEp/Ek8v2uPh1rVeqW1JdV41S3eS7utPsEA6cpGmcHyHMlKR/mRThblLp3tuoMIX4mvIbwjPszQW8Ln4r4WDD+qTS1aI4e1le3El/n95Lc/wD+upfsUX6t4uhyYNdjuPSO8tE2/wB6JkarcFSRLzjS2b+daba38fnLYzmNseZ5Uw/wanBcrXE2sfVHD95qOG3QxkqVjM2wn77RqQSq/ex5VHbSw3ZRDz7gBvq/Q7riXV5+Zquo9IUdmZo7UdYolLkthyd3wyBXn6jUfR1sd2UYY9oaaPbyXsg1C7EU/QSDOHd2G7ahPZFA6Be/nXiiJkm6+WOGjc6RDbjnBpTGoLld249B0Kk9VI8sGnOLljq24viKO40vinSeMIpZeXJL7FqUVvGJZHuMDlOqMVQPNGdhPlX0NDO4d8anGcP7x+/Z6jNo1jqt5balds1xDEoa2sHIMEcvm5UdGcduuceVd7fHnFs5zWVFVCiiEkjjkjaOVQ8bdGRhkEfEGg5+/wBBkt1RrRGubOA7o7INtmgP47SU9Rj8B6GukSxMJtM4l5UeNQk51qp2/WYG0IfwXSf0Lj17GqjpAQQCOoPY0UtAUBQFAUBQFAUBQRtWWjagaTQFQJRRUCUUlQMlmiijaSRgkaDLOxwoHxJorITiW1mZhAjFD0gnfwLKfMxqfEQPXFEtTv8A2i9XrKYX7JKgG5R57c5xmoyjsNLs7IEW8WGbrJK2Wkc+rO2WNAv1jaCG5lzlbZmVx0ydnvbR54qW6+FPHugln6XWoowZlCwWZ8hvAJP6n+FR0jHtj+ZllrWj29qI4n3SBI55kyDIUmfaJm9ckZI8hS4az0c5nn915N0r3B7djW3mZmoKVUxxRiM2kftVoy+qHxpt9CvSsy7afv58S1E2siuvuuAw+R61XKjsCqFoDFAuDRRg0DZIkkRkkVXR+jIwyCPiKIqy6Lpklg+ni3WKzkOWig+xGe+Ry9pBzVsowaNytMFhZXdxahTlLjfzpR1zjdLuyPnS0o8W+qx2UESXazXSMOdcTR++mevhTABxRWH9IvDuq65w69vpNzJbahFIkkWxtocA9Vb/ABB8jWsJqWc8bhu272VpbwWntCfYxpGN7gsdoxk57k1ztuMJWRtIyMEeoqoTbRCYopNtEYVzrV3eXT6foEa3M0JxeahJ/ktufw5H7ST91fzq16s2fZ8MWcVwL6+dtT1P/S7nxbPhFH7kY+QzSZKajKayqGSAOpVlDIehDDI/jRGNd8Ox8tlsyEjJLexy5aHd6pjxxH4oelAtjxHqunyi1vUabHRYJmHNYf8Ay8/RZv6rYai26uw1Kyv4uZayh8dHQ+F0Po6Hqp+dGlmoPPvprsGuuFo5ikKW9pKJZrqWVo3UduVCq++03uYNbxe3ocqz+69cQaJqfDkOowBYbO4tkkSVsDlBUAHXy24618/qIbwyyxzrzR6HeaNdbtSaFb6CXCzTQ/amGZBtYYHXac9GFTTyhrWxzj5e0/5WtX4kspHktbXMbCMMLl0IiA7YXPVmx2GKmrkxpaE95cv9IVxb2v0e3FrdqVu9anC2wIYsjdCZiEy32SLubFd+lh20edXjti9C4SsWseGNNtDFBEYoVAW0LGEjuGQthvF3616pfO1crymWvVYOqMloFogrQzNR0SK5lN3bN7NqG0rzcZSRT9yePtIvz6jyrVszDL07UrrSJmtXhbkxeKXT/fdFPea0b+khHmnvLWmXWW9xBcwpPBIssMgykinII+dFSUBQFAUBQFAUBQRN3rKmE1FFQJRRUCUUlBn6rrdrp+2LBnvZf2FnH77D8R/Co/EaDj573UtYuWwY7po2wB19htiPL1uJB+nyqIgOp6RpWqNazR3eoasFj5lysRkJMgLBExhV8Kk7V8qILnjOS1i5zac0kcxuUsQjjfI9qRlSCPDuB6UoRN9JuhxncRiIXa2pcsBhTGrPIR/q2kCle9KVtT8IaTN7S01vFLdSszQ3Lrlo93+OD1FY2Q9WPV5xVTNHexqtleWMSF2tnSZIz99cA/xwaJu5jL1NtuFtFkgWe3A3yxRRG5VRloY23Bfgeu1jTbDeXU53U+v6ug8z6mtvKzby9Vre+5agrEvISUdd00nh2D1wSM1mXbDDs0IYBFBFCO0aKn90YrTnM3KTbRkuKAxQLVBUQVQUBUCMyKpdztVRlmPYAUVjzTG5WOa4DmCfpZadH0aX9+Q+mOuOwFZeiIrt5d5Tx2V1tP2NnCPux8svj5tlc/lVpjfHuhSzuUm+yiFpdHxLJES1tLjusiH3c+tRvfFesfqv2lwLmHft5cikpNEe6OO4/wCVacssaPkdIo2kkYJGg3O57ADuTRhz97dXOu3Uul6ZK0WmwELqupx/ez1Ntbt+Ij33Hb51qOGe6lxNwxqEkdvb6DFHBa2tnMscWXVRMXTbs2Mv2m0HDNkZ71LFWzb6UReXIVLVrdRi3TUMhdoP2eHh8Rfb72emaKg+sePY57azDbr69SX7K6SJeUYlDGVeXnMRb7MbvhQZsdl9Iz8SS3SrcCEwwotxciIYYRybysanZ4ZGHcdRRGhHqXFcHEtnpV7clwZcKixx/bW2X3TSkDwt0XG3pUHXXVpBcRGGeMSxN3RhkVEULHS2sdRFzHKZI0H2SyZMi/uGTu6egftQdLb39vIviYRt5hjjv6ZqN2dqFkl7Zz2jsUEyFOYuN6Ej3lznDDyNGsZqbeQ8PWV5y9c+jfUGe1humk+prpg8kYlHjkhEjheb0wxx6ms62G6H1p1IicdaOa7un4Z4C17R7I2tzdJIJpedcezo0fYbVRT6HGTXg8CYTquux1ct1eToYOHY1lE0qEsnUSSEttHzbtWsdGXjnWcLpdnJxx9IB1Z2lj0XRvDpqFZY0lRWw1xDOp2lzIMMp+7X0MMdsPRnl4WnXnl3/wCnrtHzCVQDvQOohaoWiCqK1/p1vfwhJMpIh3QTp0kjfyZD/wD3NGZhgW82o6Nfcsxhmlyz20XhjuQOrTWy/cmH34vPuK6Wy6u0u7e7tkubd98Mgyrf/wB7GipqAoCgKAoCgKCBu5rDRKgSiioENAlFUdWvJIbZ0tnVbth9mXG4L8SKg423025vXke4aSK1lP25fpc3RHnIw9yP0QVGW7BBHFEkUSCOJBhI1GFA9ABQQX2gaTfh/a7fmc0ozsGZWzGML1UgjocUUy34V4fgklkiswGmzuyzNjcQx2AnCZKjO2qHx8L8PRy38yafEJNU3+3nH7XmDD5HYbsdcUtWiFgtbUD9nb26ADPXCKMD4npUWIVwUu5EurKTZcQHZKHUjKHrtYdD8VNHWq4ntJLmCC0YyxXq6fzicpJtMTN67Wxg+uKLjMz5Wz7651DnRtFqNvOgGHjhYoykkYbaiyl+mRg4rMu2GONdpadvbSTTJLLF7NawEm0tPPcf6R8dAevQVpwyyqPWZ7tGq4iqCiigKAoCgKgz9a1QabaxzkdHmSNjgthT1Y7R1JwOgqZTTrpae+a9mWeIbXV7k6faGTkTCPczxPEw8fjXxgZDKMVndbv4E6cbp7l1fVpNN1Ke65LzrFDLiONNx2QIrbBjtuZ8sfQUmaTS0t+NduY/Vo6Tqcl7NcBo3jRVikjSVNjqJB1Vh8x0rUS5amntX5ldoZFRtrlSFYdwcdDVcoUbQyjUPtF2tc2sckq+fNjOxifmCKjpl9P2kvEGmTapod9pkM/sz3sRg9oxu2B+jHHn0rcTy4yh4Z4a0/hzRodJsGke3h675WLMWPc/DPoKTNmMU0yKy0Qj1ohu30oG4ohpHSiGFagjZKIztU097u35ccgRh12uN0b/ALsi+ny6igg0biW4sZPYNTD8qIeIud8kA/Fu/pYP3+6+dGolc4s4H0TiiH2iZnTUVgMem6hHI/2BPiWRFUhe/wCtIl6NHqMtPt282B/6H48nbrt8od7YsObL7kaYuE97+mbxZ+7Vt3+N/pj9/wDSA/QpC9s8Mmu3rF4413cyUjesu6RiN/XmRfZ48u9W1+O5+mHRPecDfR5awWJB0nTb6Vmhc8ySASgDIJ8WwkdasRMvFq685TeXd01ne2l7bR3VnMs9vKN0cyHKsPgayysVAlUKp6UC0QtAtVBVEF/Y219bGC4XKZDKw6MjD3XRu6sPI1YlmXPQT3+i6i6upk5hMk6IPDcxj3riIeU6D9on3u4rbLrbe4guYEuIHEkMo3RyL1BBoqSgKAoCgKAoK7e8axLRDUBRRWQlFc3rvFPssskFoygWxHtt2/iVGPaGNfvyt6eVEtHEzygSurK7jLK/vDPkfjUROqUEoWinhaqngUDgBRTZoI54Xhk/ZyDDYOD+RqLE0qjRYhI1wlxOL1sbrvd4iFGFVl9wqPTFKdPF8qivRJa6c7XDS37JczMBGnhwip54U58THqaUk5+UcM3hDXBq8eqSC0jtTYahPYDl/fEBwHPxNbnGnKMpyb9ZUVQUBQFAUBQFAUEc0EUyhZV3BWDr8GU5BHyqNRNK2p2rSRvcwj+eJsZG75ETb9gHlu6ipMNaeXlPZWZ7VbpNSYB7G5AIlP8AQy42ZPorr0b41G+a2+cfq044ogzyxqMzEM7r13YGAc/KtOMyqT3nPi5WmyLNO55fNjIdYfVnx6DsPWpbpGNfUSz2zX1xdKS0aKtrE5+9yyS7f3jikGXERH91+tOQoCoEIoGkUU3pRDSMVENIqhhFREbJQUNQ02C8jAfKSxndBcJ0kjb1U/4jsaIz9L1i80Sc2l2hNp77JGMqB96a3Hfb5vF93uOlVYl2qSRyIskTB43G5HU5BB7EGstH1RlcTcM6TxLpLaXqsfMtjIkmB3yhz0+Y6VrGaZyxtjaVdz8KX1vw9qchfRbluXoOpv8AcPlZzn8QH7Nj73bvWp55SJp2PY1zbc1xxrOo6ZFpvsdwlr7VcNHPNIY1AURlh4pcqOoqwjPn49v7R5Q9nG9ss3ssN80hCFgI900xAwsX2ncVRXm+lMpeG2FvbiM9EunlZYQwZVYuSMhPH4TjrSkMl+lC9bOzTmjZVhlWNPtJXVpArjbjwhgcoT3HWqEh+k69E/LeCC5592IYeQzFVjflou04G9leTx+lEJYfSZqix/zy2hnmzkrGWXmdQpjthg72U9Wz2FUdXwvxBd6sLuO8tRaz2vIbwMWRluIhKuCQOq5wag09QsIb63MEuVIO+KVejxyL7rofUVYlJYOm6jc6Tey294AIcqbxVG1ELnC3UX+qkP7QfcatsuvzRRQFAUBQFBA3c1zlo2iioEqK53ibiAW4ksraXlSqoa+ux19njbsB6yv2UfnVSWLpWlgtFczw8pIutjaHryge8j+sr+Z8qyjcRKCQCingVVPAzQPFFOAopcUQtEALDqq72HVU7ZI8s/GivPvog1F7y24kzay26/XFzLmXp4pG/Z49Vx1rrqOen5vQa5ugoCgKAoCgKAoCgKgzNQ1kWc7psUiFFkfc+12DHGIl+8w9Kky7YaW79/5WLY6csM9xBIpt3Jebr4FOPFlfu58xRnLddT3UFjs3QMmm3KI4yiodgIP7oYYzUdLn1gllo88YkiTda2sgVZMsGnZV7KCoAQdfiaRC56sT7z+jYiijiiWKNQsaDaijsAK088zZ9VBQFAVAUDSKKbRDWWiGEUDCKIjZagp31lFdQmKTKkHdHKnR0byZT60Rf0eSO3iSzwFQe4R06nv07dTRqJatRS1RW1TS7DVtPm0+/j5tpcLtkTz+DKfJlPUGrdJMMThfVL+2vJOF9afmalZpzLC9P/TbMHCyf/UT3ZB+dayjzZxnyQfSXrGs6botq+kxs873I5xWPm/ZIpZlAw3jfso8z0zWYaU+KtV4klms20SC4NnNpkl3JGm2Jkk3Jt3K6PvKqTmLzqwKsfGeuXLXntGgx3NrZtGdvLdZTg7I3wQQd7EMPwrVRag4y4vl1Wey+p4IpUnjgMrLLtTGdxYj3g2MoR2oILHj7iKa7063+pU+1uGimlEUiIRuUYhY/eVW3Fj0OKI9E2ID0VfCfD0HSpClFVAaCjrWli+gDxBfbYATbs3und70T+qSDoRWolJhS4Y1XqNPlJ2+L2Td7ycv9pbOfxw+R81wa2zDpKiigKAoCgrt7xrDRKypKKztc1Gexsd1rHzbuVuXAG9xSe7yHyVB1NQcdpdn7bILl2MllFIZIWbvcz/euX+GeiCoy6FFoJVFFSAVVOC5oH0U4CinUQVQUEc1xDbpzJpFiX8THFRqImeyla3GjWolFviJZ5GnlIVtrSP7zZxjrTcvhSvRTQzJzIXWRPxKcijMxR9VBQFAuDQGKgMCgXFUGKAwKBjQxMyuyKzp1RiASPkfKotq9xpVlPJzZIvtPvMuV3AdcPj3h8DUprHUmFG41G8TjCw01WHslxYXVxKmOpkidAhz8AxrdcOV8teo0KKKIKAoCgKgKBpFFNohpFRDSKojIqIjdaCneQzSQOkEnJmI+zkxnB+I9PWiIuEtblLnSrvKyISsG85ZHXq0BJ97p4o281+VGodTRSigxeLdDudTsY7jTmEWuaY/tOlTHtzB3ib9yUeFq1jLOUKFzqMvEfDFlqWmTXdlcNNElxBbPskjbmhLiOTof2fX/GkxRE2zb3iTj2yubaOO09ojkuZEEfs8jH2dJjEpaUH39oEhY4oFk4o+kG0ngiexF2/MYERQOnNDQo6gE5VArsVJJ8qqnPxDxrLp3tcXijtzE8wNnLbsxZ/tEG852xD3jjrRFeLifjq69muYI3ntmI5IS2kgFz0V2zu6xhCSuT71ET2/E3H0vLkS0EtvGVaRmtZInl3SRo0YVjlOXvbxee2g9B86KDRCiqOd4lsBE/1ijtCjMntMif0cqdIbn5LnbJ6qa3izLc0m/e9tA8qcq5jYxXMOc7ZF94fLzHwoLtAUBQFBXb3j865y2SoI5pooYXmlYJFGC0jt0AA7k1Fc/dXHtj7+8LDwDyKn/nUQkUaqoVRtVRhQOwA8qInUUVIo86qngZqB9VTgKKWiCgWioLy6W1gMpXe2QkUY7u7HCqPmaTK443LPWKb2rYAlzqYAa4uZATFAG7Ig/wAB+ZrLrfHpj/la9hvNvXUp+Z33BYwn9zaen51aY3x6Qg9hvd7yII47xOsc8XhjmH4JY/L51Ka3x/b/AAv2k4ubdJlUru95D3Vh0Kn5GtQ55RUpsVWS1AuKAxQGKBaIKoSooxQGKDnbv/3iaT/1Vff+LFW/Jie7oMVhsmKoKAoCgKAoCoCiGkUaNPeiGEUQ0ioI2FEROtEYPENiRjUId3MhA9o5fv7FOVkT9+E+IeoyKQOo0HVRqWnrMxUzxnZcbPd34zuHwcHcKNtGgcO9BykZ+oOODFjbpfE+Xj/DHqMI8Q+HOj6/MV07x9mO0uuycVzaN3HHeqp56jr1z3ogHToO3pVC5PrUQVoLRAKoGRJEaORdyONrKexB6EUgcxpzto2rmBieSNkM5c+9C/S2mye5Q/ZP+VdGHX1FFAUBQV2941yls2iuU4y1RNwsO9vCoudQA+8M4hgHxkfv8BUSUel208Nrm5YvdSkyz+gdvur6KvYVEaCCipQKB9VUWoSSQ6ddTQ/tY4ZHj8/EFJH8aK41L3jw3mlQMXWC/Vn68gTjZCHbcwVo1Xceg71Rs67xLqemaj7JFbRPbxwQPLezlwqvM5TLbAfCu3LY9aJbnTxjxBLFeS211uvPaLiNbDkFkhgW33xzhtqsQHx397NUOn4z4wdbi0t7N/ri1MLTQLDuQrDDzbjYTgbZum0+WaFurvddmzpc9jazXEF5C9yIE2rI2Au2Px4AI3kn5Vzyl6NLTjKJua7K+m6re32vx29zbvaxxu0iW820yK3LAxlCV+9n86zE8uuppRjhcTbP+udegvLr2K09rLSRHl52A82dklbrnJAUL+7UuXXwsJiLmu/+HQ6Hc3VxBcm4GOXcyxx+fgGOmfPacjNdMXk1sYiYr0W763nmtGSB+XPlWjb4qwP6EdKsueE1PPY2zULdX6oNq84Nj4ugJ/jUhcu0fZcxVYKKDBi4ut5pLRILSaRb6K6mtZhjlslp3GfxP5Cqiy/EukRwWkzyMBexCeABGY7WwB28yTgD1rMy7YaWWUcIJeKYoxLMbSQ2UUnJNxkA8wpvAMZwwz2+dTc3HT+/KB+O9JXT2vOVINoizbthZOZKSOUQezKFJPwqb3T4PLdTUfXdIXk7blZTPgosX2jAEZywXJUAHqTWtzh4OXp2QHijRtm5HkkO1nVRG/VE++Onufvdqm5r4fNTl4zgtktWvbGaAXfKePaVk+ylz9oceSY8Qqb3SOkmbqYmk0HF2mzX9jZqrbr4OVkyu1NrFUz/APUKnbiruZy6XKImfT9/ohuh/wDiLpI//K77/wAWKusdnjnu3LS5S7txMgwpZlw2M+Btp/wrnjlcW1E2l2n1qqhnubaEgTSBC3bP+NScohLMuby1tQhuJVjEh2oW7E4z/gKmWcR3JmkiujKHVgVPUHPrWlO6eo6d+tA0yRg4LAdN35DuaWBHV1DIQysAwI9D2NAiyxs7IrAsmA4z2J6iloUOhYqCCy9x86KZLLCnvuo9OvpSwvwoI+lENYedBGwqIgYd6IxNH5mj8RC3RW9muBtUAeEwk9PhmCQ/3TVWHc1Gi0GLxnpV3qWhOtiu7UrSWO7sOuPtoW3AZ8twyK1jKZQ242Zo1Zl2MwBZPQ+YrIU1VOqoWoFqoKsBfKiBe9UOFBicU2UL2i3sgOy2DJdbe7W0vSUf2ejj4itwzkvcP3ktxY8q4Obu0bkTt+Ir7sg+DqQwoQ06AoCgrv3Pzrk2hnnht4JLiZtsMKGSRvRVGTRXn1oZtR1JZZhgMfrG7Vs53P0tYcH8CDcR61ll0aCgmUUVIKqnrRThRTxRC0QZ/j3ooyaKayIxUsoJQ5Q+h7ZFBU1CMxql3DGDJbPzXUDxMhG2THx29R8qkt4T5T5oUuEtJWuAeZpt19olwvXlFveBx9xu/wADUardx/FC619YQwGUzRiJRnwkH9AO9W3PZMyry3QnVJ93K0+AmS5kcFGJTtHtOCOvejcY1x5yn01JuS08wKy3LmUoe6qeir+SikM6neo8luqwVRQZVvw5Y29nDbxkhrNbiOxl84kufeA9ceWaqKerWNpbw6ZpFvae0T3Cey2u6Uw7Etxzd+9ckMCARjrmpMW6Y6k49mOuocI2rYvLK754blSRq7XMDXmwBo0bdh5trd8VNjc9TmkPEH0ew3D6pJbSR3iqUkikjO88ocnxR52kr+z3etNqePnVXwgbiXgAwWyR2l4sUJQCWKNo8GXd9jLJuG73DlSabD4jL8zG1TgKESlob3ZA7QSyRGVowSNy2hO4dCo3KmMU2NfFZ/uP1+7oeH9N4eurSK9s7eX7OQoFuyxljaDdFyyGJwFyenam1MtfOVq24V4ftYTBBZKke9JB1OVMRym09xtz2FNsGXUakzcypXf/ALxtJ/6rvv8AxYq6R2eae6zbcL6WsR9qtkmnZ3d5PF13MSPP0NeXHpsfOOUjThL/ACa0H/Qk/Vv+dX4fD0Xw4MvdDSSKGOz2W6wghPe3Lu65Ug5/I9KZaXpxROKjf8L3V5JFzblGii91SpyQST18s+KuWfTzl5szp2eeGAX8UicvcTsCnx+9jf17ru6fKtfDr4ZqcMye08yedZUPR0wfFjtupHT88nhk/kuQu1JU2bccpwShOBncM/DNPh08NY07QXs7tpzPvDRcsYyD2A+WBjpWtPR2zbWOFKg4Vk5u/novjVtsYZR4QBu7+/0rHwzPhrA4d27Nk3LYY5hUHxDrzAf61a8BfDQrwvKHd2nQlj+E9PUj0JrPw6eGWbhl2eN/ac7HJwd3ROm0DB7qBirPT+6zprmlaa9jDJG0gk3vuXHl+Z6mumnhtXGKWz2rq0jYURE4qCBsg7h0I7GojctpudCr+f3h8araWgdRSiiA1Q4dqoKiFFVC1YC0QL3qhwoBlVkKOMowwwPoe9UczobT6dq4speqdbMv3JMQ5ls7H96ElfmK25usqNCgKCs/c1yluGBxe++whsj+zvJVFw3kII/tJMn5LioSx9CzJaten3r5zOPPwHpGP7gFRGugoqUCgfVVJRTgKKdVZFRRVUUQUBUCQwRQqViQICS20dst3/WizNsyXT5pmPN0e0LsMGbeO35LurNO0Z1/FKaz0cRhfaXEgjYvFbrkRKxOd3iyXb4tVpnLU9Gl3quR3QUC4qhagq6lpGn6nAsN9CJURt8fUqyt2yrLgg4qitFwpw3FMs0dhEjoAExnA29iB23dO/eiHy8NaBLzeZYxMZ42ilYjqUeTmsM/GTxfOoI5eEuG5bP2KSwja1ypMRzg7AQN3Xr0J71QfyT4a53OGnxh+3nj57e2R60VowWsFuhSBAiszSMB+Jzlj+ZoH4qDm7z/AN4uk/8AVV9/4sVbjsxP1OirDZCKoSoCiG0U2qoqIKAooogohDRoyiGMKIY1BGwqIgPTr6URlcKz+w69c6dI/huNyw733ElPtE7+fLLD+zVWHZio0cKDL/lRoAvhY+1rzmblq2DyjL/mxJ7u/wCGaluvgZ1dNU1pyKvaqFoipqOr6fpsatdy7Wf9lEoLyP8A1UXLGpbWGnOXZJp+o2Oo2iXljMtxbPnEi9sjuD6EelXEywnGanutVXML3qhwoFqjmuJreRb1JE/p4uZCfS5szzYyT+8m5a1DEungmSaCOZPckUMvyIzRT6AoKze8a5S3DE1mTdciL7qL1H9asySqIo6ADA8gKIsKOlFSLVD1HWin+dFPFAUC1QUDXdURnY4RBuY+gFBmjijh0oJPrGHYSVDZ6ZHcfl51rw8vRnfCY65oqzPE17EJIgWkUt2AG4/w602Su6F2yubW8SOe2kWaBz4ZF6g9azMUW5b6Ob6+vLfiA3dxJccjWryGHmNu2Rq3hRfRR5CtZ/6ZwdcKw2dQLiqFAoHCoFxVBigWiCgTpQGKKSg5W+urQfSVpUZmQSLpt4hTcM7mkiKrj1I7VqOznP1OnIrDoSqEIqBKBDQNNAlUFAUBRRRBQMNRTH7UQw0QxqiIHFEc9rLexavaagCiHo2X/FA249fjEzVR33TuOx7fKo0ZcRc63liwp5iFcPnb1HnjrijWM05Ww4O1ixFgbe7s2awWZIY5IXaNBM+4csbsjZjGT1rO17M+pxyu4nn3a4g4w87zTz/2Ev8A561y4Xp+mRwh4vx/len/APcy/wDnpyXp+mReTxh/pen/APcy/wDnpyl6fpkz5+FtYu9Se/ubm0jmktZbSSW3jkV3WRcLnLEYQ9elTa6Rr4xjUX3tDdQ8X6Y2nfVltHc2WnQCO6tLfbCtw8uV3IrZ/ZdG6keddIebUyvKZV7QfSNDLYxXCmZNOmL30wdMXsU5GFToDmEE5zjsO9Vzdx96inCgWqMviaPOmC4BI9iljuOnmqnEi/mjEVqGZScNKYtLFqevskkkA/qox2f7OKSkNWiigrN7x+dcpdHBNfzzaxgbgtxeXRPX+jtwI1/JiMisstpO9BMtFSDtVVIlFOWin0QUBVBQFRXP3HD1/th9jngV09sVzMjMu28IPQL5rjzrrGcebnOBttwbHaWsns82/UF3ewzT7niiZoxHvMOdpbAqzq39k2NrQNPfT7C3tZNhlQkyOm7Dsxyznd1yxOTXPOblrGKct9F3+TcS/wDX17/vVrP/AEzp+f3duO1c3QooFAoHUQ6qoxRC4opaiCqDAoEIoExnpQc7ccEaZNxxbcWuM3dratbrHjpvPuy/NVyK1u4pnbzboCp9Kw2aVNA2gbQFENoptUFAUBUUUQUQ09qNG+VREdVDCKiIXHSiMLiiOE6ek0qBhBMpyfuh8xsR8w+KDqtCulu9FsblQVEkKdG7jAx1/Sq0v1FKKANUOA6UBRCkgAknCjqSewFVFe01LTb3d7Hdw3Wz3+TIkmPntJxSJaywnHvEwtVWAtUOFAtVEV/HzLC4j/HE4/hVRicJXqzXF4o6c6O2vAp/10Wxv9qKtSkOlqKKCsThyfQ1yl0efaY/Mvrbw9reaT/vJun+FZZb6UEy0VJVU9e1FPWinVUFQFUFAUBUDqocM5wG2t91u+D5GojhPon07iKzg4gGs7QZdVuHjVVxuYnxyf1W6YrpnLGnbva5tlo0eKqFFAtEOqBcVQtEFAlFFQcL9MeuXek8HsLKSWG7vZVt4pocDb95snyBA8q9PS4xOfPZ5uq1duLwuy4m4vh1Ceb6yuyZ5knlw/veErn0/LtXow0IicrrnsxrfiWGWOnEXePfhA+v8VS6QlmNSuzbRqqhOZ0+zkLnrnP51znpv/Ft43O8fienj1U5zGWz0r/Tpfo91ziG/wDpI0SXUL6e4gDyqUeTp40OAV7VOq0e041Ud06TrcduWGV7s+Y4fRBHiNeN3NNAlAhoGtQJVUUQVBwmoa9qs15KPrJbB7e8WCIxAvbiNgWMj5G6RvDtK9ADXOZfRw0cYjtdx/d0q8U8PBQG1GNm82wwyflit7oeT4fP0L/Kfh0jpqEX+1/ypcHgZ+hP5S8P/wCnxfx/5UtPAz9GVrXEqM9rBpl5FsuJlhuZUy06BzgGNCNp+JPaszLrp6Heco7fkoaTxOlglnFqt6Z/rG5eC3De9bqp2jnOdpbLYGcedXFjqoiMuIpJ/wCkHh97eKUOQJLw2PcdCP6Q/uEEGtU8zcuYY5UaKVdyHuD8Dmso2tMjjjsIUjG1AOg/Oq0uUVyN5rXGFpqN/Mtqs2lxXPs1uJBgAMqES/ZhpSgJO44+VaQaVxLrt3wlPf3Fu1vq6zHfbNES8MDzFUfZ9/EYyPWlBh4t16KZbW1sW1RfdS9kjkty5PaQoFKiNfdJHUnsMUGrwfr+razbXUmpaY2mSQTcuJGJO9cZz1wcg9DRGL9NQ1Y8AXX1cJDiWI3ohzv9m3faduuPX4Vx172TT6P4Vs8eN37l5b9HEyzcbaJ/JiN12n/1sV/Z+z48fM8vl8a+f0kZb36H8V2+Blv/ALfd79xBqkmlaPdahDZy6hJbpuS0gGZHPoBX134/Tw3TEXSLhQ6s/DthJrBP1nLEJLoMMFWc7tpH7oOKq623fO3s1hRzOqod36VUcvwtAI7yNvP2V4P+4uX/APPWpZh1VRoUFOfPLlx32vj9DXKW3mvDTSNqkG/ofqiEsv7xuJM9KiOrSoqZaCTyqtHjtQPWqp1GRRRQFAUBQKzoil3YKijLMewA8zUFJbi9u15sO20tCMrPKMyMPxBT0UfOo6bYjvzKMNFt2DWjzP8AOfZY/TG2o1/+U73d3ZgPd7ZrTzuohgoPxOnXw/EVbZjGMu3dodCAQcg9iKrB9Vko7UgcRxPxLqNteXVvDqBsp1u47ayiEQZDmIOXnkIbbH1z8ewqo0BxHqUGnXTvsk5GovZi/kUmIRBd29lj69G+z+dZyd9DTjOUT8aX6vgxwxgyBXLxXGIB5c3C9TL9zH51jc9Hwse/6c//ABROvcTSpIlhdu92xnW4SSHwWpFyEt/ujO5D1Hp1qXLr4OnHeOOPPvxylfinilmldLKVVsLqR9Rj2DpbRhFKJ5vklnUr1IFN0p8Pp+veOPuu399xY2s3sunDfplmIZVRsASIYt7oF27yzeuelam3LHDS2Ru+qbUbrjfXBayNDbRSvg+zyRxy4uT0zyAw6GHOW3d8Vmc5dcekwvmf8cff7ojJqt9b6Te6/E11pMthbyssCEP7WwzI0q9vlit425Z44xllGPeMp/JjXVlb2S6o2n2l9Bw3Nme8nj8cwkZSHEKHLjp1GOlWGo5q9u5Da6El/oGk2OhG8sy5hkngnjDKUU7gJHYZySASaq5ZVlM5VKzwxZWOme3QalpN5bXMNzJ7Ldv45Zi3VpQ34Sx8PwqJq81MTHZ0vDeq63b8I3epa9atbyWpne3t3IMpto/2ZcjPiejza+3d8vKC54z1C0upYryziWKOBbrmxuzDZzVjkXOMF135wO3n3q04rmtcRX2k6hMJYI5dOht/aiY9xuGBkEQRVOFyWb1oKkn0iaSL46elpcy34bb7NHyyegYtk7sDbsNKC2/0g6Pdzvb2lvczTgoI4QqKz7wWyAzDAABOTRbQW/0i6dcctoLG6kjnkeK2AVQ8hiZw7DLY2DlN3pRaO0+kiynMmLKZ/FKLeKLaZJEhJ3P4iqjwgnFC2xonFNjrM5S1hnSMx86C4lUKkqZAJTqT03edBsYHoP0FQNbkL72xfntH+NAwvafii/VKNRZm+1/FF/sUSpZGt6nc29zZ29lHF/PJOUb47XETEZA5Y6knHQ9qzMu2lpxNzPl5Mm1v7K4t7JeI0t55dYZrS0k2A5i7gT48KFiPLzq42z1GOMZVBTqfBTxrNyIsTzfVP7Md1+6R5J28XyquDY1Gc2tlNOACYELAHt4ayjU4cvHu9LSVlC4d0GPRWxmq1DVorLbiXT4re/lmYQ+wzSW+12AMjxIHIj9cg9qqMIfSfoz3gihhleLmJG9wfBjcEPusAenNq0tuo0rWLHVrMXljIZLckqGIKnI+B60Rc70AzIqlpCBGBlye2PPNEc3wPq/1jDqHMht7eaO6kES2yhN9tn7J29SfOkPR1OlONfZ01V5i1Q4VQoohw71Uc7oQxqIHlm9//wAkVqUh0lRRQVmGWI9cj9a5S6PPtLiMV/b9O9rJEf8As5un+9WWW8lBOO1FSCqp47UU9aKdVZFRYHbqegHcmikVkYblZWU9ipBHT5UQtAUFS8T2m9t7M9YcGeZfxbThFPw3dTUl0xmosyONdSne4nO+0icpbQfdYr0aR/Xr0Ap3WZ28R3X+VCV2GNSn4dox+lVztU5Q0+6iEX+Q3Tct4e6xyHsV9FbsRUdL3R7wk04ciS5sRnZAVeH4RS5IX+yQRSDPmp9WgK05FFAKiK7SBQHfAdvM47Z+VELFHFEmyJBGmSdqjAyTk/qagk3H1qoMmgMmgM0CZJNFcPqH0w8FWeo+wNPI8iXBtZ2VDtQhSS3Xuoxjp510y0sor+o0qz3V/DHKmv05cCG65HMnEfJEomMfTJbby8d9w71fAy37PMmY8LxPK6L/AOm3ggWL3TPMuOfy4tnVxB5jyAf7uaxjp5TjOXlDeeNZ44eeX+3V2OuQ3/D0GuW8E0sM8AuIbZVBmIPZQv4qxHJqY7Zr0Y9zxYt1bzW8/DWstDOjRyp7OOqsMH79b2uW5mG40bawHCmsB5OXz5RbrvlEZBAfxeZUbvWm03L1xxLbXBJuOFtWlLLsJa2X3Q27b7/bcM02m5UTUdFjujdR8HamtyzMxl9lGcvncff88mm33N3sia44eO//ANitR+027/5qM+D3fv8ATHwpt9zd7GXT6BcpaxvwhqqxWkpmiijtgq5O7ocP2y5OPWm03eyWS80KXfv4M1I8w7n/AJqoyR8nptL9luDiK2gcNBwtqsTAFQVtVHQ9SPe+FNq7vZFw99IQ1jiC70ZtFvrV7WQp7S8f2Q6ZxKfuN8OtWcKSM7l011p9jd7fardJ9nu7xnGa50645zHZB/J7RP8A4dD/AHalNeNn6mnh3Rf/AIdF/dpSePn6s3Vo9I0b2eaLSle4llEdu6rtRHboC8n3B8akuunuz43cMnT7TR9TY2+r6ZbwTSPJb2DxMyrMY23SNAD4kKsvvUxZ6jGImOb4SjReAXWEpDbbLlzaW+CdrTR9GCj/ADg2dW71p51PiHiRm069tDo2p4KmLmiAFT125B3djV2sW0uGOLJbfRYIzw/q8jZkJZbcEdXP79Xa1uS2X0l8/ik6E/D+pREqjCcxe4H/AM8uTsHxzV2cG/lsi24M+s7oqtq2oXc5trpSdzPccvcU2ns/L69PKstCWx4Mn1hUmit5NUyBsOd24AABvu5xH0B9KCzBPw1osAt7dobOJmdhEmcs4ba5wMkkMcGg04JoZ0DwyLIjAMGUg9D2P50QXEEVzbS28ozFMhSQfusMGkLjlU2yOG9A0HT98+lStPlRAXMnMACddoqu+vr55fVw3COtHmL51Q6qFFVDxRHNcNyK+oEeey5l/KS6YD/crUpDpqiigrH3/wA65S6PPuVLba1EpZcRXd3bkfuy/axD8hjNRlvJ3qCZe1FSDtVU9aB60aPojneIbHiWfUreTTJCtusTD9tyljmz+0kXDc1dvQL61UYVxw/xvc2r28gYwSW7RRwyX27Y5zvMx2fa83ptH3aBsnA+t3F97fAsejMglks7OCXfHFP7OIldwoVWEvUOAO3xqlLXDXCvEthfafqV5LEZoYksLi0RiVFokfvBvvNzstjFRXb1BVJCazEWPSeAqvzRsn+Bqebf8H2kaQdsElq37W1kZXHwJ3I3yIPekLq979V6q5qt7JmWztl6yPKJSPSOPqW/4VJbxjvJbZi+pXpHuRiKIH94As36bhRZ+mF0Gq5nUDgaoAcUQ7NFFQFEFFVdT1Sy0ywnv72YQWtuheSU+Q+HqfhVXHGcpqHzzecAa5LfRXU8xRNTuGkXUHSTlgtlg0pA8OVOK9eXU4TVx2eXDotfHdtzjnuqL9Hd1Jq0lukwNvbxANe8ubksSeiI23rjucVficd26uVnoNfwdm+KvsSy4JuNRBt9Ou1vkEtxFFy1kMfhwsp34wN7dgeprMa+nETFcS1qdF1W6Mss43Y1T3Pg2eKw0bTdBuMw39pbiPlv03bfwZ79K8s15dno25VeU3Pq6LJoyTJqITcaBuT60CZNUGTQGTQGTUCdFBAGATkgdOvrQJVGTNwzpMsryv7RvdizYuJQMn0AbArNO8a+UR5fkjPCuj//ADP/AO5m/wDNSj4jL2/KGdquncNaaITcLczSyyAWtrzpXMsoOVABbb39ak06aepqZdq9+GZbaRpmuTPIVutMvLKRltnjl3RLMX3ymJvdkPcMvlTGXPqMKqbu4P8A5A6FGE5N3PHFC4eyQS5EVz03upPvF9nVTWreZo8Sux07l79hmljUnODgNubH5LUHT6BBJb6JYxO+9xCpd/Ut4s/xqttBemSAAW6t8fnUHLT/AEeaZPq11qRuLiOW7lNw4hIQrIycvcjjxA7RjNatKRyfRtYsbcDUb2JIU2PJHJsuZOrHLXA8Zzu60sMufou0KXDJNMs2GEkzsZGky6vmTJ6nw9xjNLGnw7wfa6HeXFzBcyze0RRxFJMY+zGN3TzOKI2L+2e6sbi2SUwPMhRZl7pnzFWGsMqm+7m9L4TZNHvrSz1jIuQsaz22MRuh8TdCfE3nUevU6n5omce3q2tA0i502GZbi8a8aVwylugUBcYGSe9aefW1Iy7RTVo4lqh1VCTSCKF5D2RSx/IZojluCoXM89w/3ba2hx6M2+Zx+soreTMOtrLQoKre8fnXKXRwvFsJtNVuLlY2ZSINQXHQboG5UuPjsIJqMy1wRnp28qgmU0VIKqnr3oJPOinCgWiCq0KIKAqCC8tvaIgoflyxsJIJR91x2OPMeRHpSYbxypTeWGa5QXDHTtUXpHIPdceik+GRT+E9RWXSIqOPmxWdmtYwbm2A/wA6I2z/AHc7avLHyekq8MsUUkkent7dqEnSe7c5Rf67DwgL5ItRuYv6uI9P3/lpWlqlrbrErF2yWkkPdnb3mPzrUOWWVynzRk4GgWgXNUFAtAdaIKDO17RNO1zTJNN1CMS28hV+ozh0O5WHyIqS6aec4zcMy/4Y1bULJtOu9Yk9gbG7lAJNhT5P+VJbx1IibrlWtOFeIrO+mlh1wNZmJYLe1aEfZqDuY582Y+dGp1cZjtybLwFDzrG7tb+a0u7J2mbl4EU0jdN0ifDPTFDx+9xdrEHCs0vEFnr+qX0lzeWEbx20KeGEczoWZfNsHoarM6vy7YjiXQ9aOJDUQlUNNQGDVCUBg0C4NFIQaISimmoIbiN5IXjSRomYYEqY3L8RnpQieWNPw9LOES61W6niR1k5bCIAlDkdQue4rNO0a9dsYj82fqXCd7LJbSWWpNCbCSS6sldQwFxI+4hiOvLwSuB161qHLPPdNs3+Q2ppGsI1l9kU/t8bctc+1nG7Ply+59etLc2zrOkz6pLaxpGH2bzjdtIeQcssPlGz1B2oRVCovuqAq/IdBVbONBxWucMcU3lxcvb3v82lunlS13bfsmEQAz0/A3hrSNHhfTeK7K4WPUrhZNMjh2xQhtziXd3Ldyu3AAz0OaiOmFRS1UAqo4j6INA1fQ+Gb201W2NrcSalczpGxBzHI3hbpnvXPRxqOfV9P8V18NTUicZuNsO58q6vmHCqFHeiHDrVFLXZzDo904G5imxV9WfwgfqasJKvwzGnsMs6j/KJ3bPqE+yB/SOrKQ16iigrN7xrlLpDH4g0qK8ijncnNuJFK+Txyja6n/GpJLMtIo4II4EyUiUIhY5OFGBk1llbQ9KqpQaB9VUlFOBop1GRVUUBQFAUA6RypskUOv4WGR/GovZWOlaaAzezJuwSOnTPy7VKa8TL1Y2lz61JpLy5aPbbho9oC/aFD15e3r1ry6c5zjfs88ZZTytpqusxLcLJZPM8OF5gwIwQvV8e8wbv0rfiZ+i7pOXWdWeIGOyDEy8sXWCItue+z3+v6U8XL0N0on1/W43iRrBXL7SxUMB4gDtGfPr3qeNn6Jvki65q4kkdoty48KKj7UOB0OepIz1NTxcjdJp4i1xcP7Fu5oUiPaw29Oq59WP6VPGz9DfLT0i+vrq6ufaE5aKqbIgCNrEtuBJ7noO1dtPKZmbaxmWpXVsVUFRVe+mu47SVrKJJ7wL9jC7bFJ/ebrgVUTAttG7G7Hix2z54opKBKgpawk0li0cEPOkcgAA42/v9xnHpWNSJrhjJlxaPLsneFn5fJ5dsrNlydhBbfuIB3Vx8L09GdpkdvxJb3MmMyJzIlDZHjiVcbjn3T6+tIx1IkrJZvrKeaZ7q1iIkkh2pvYqBIWxkjPktbzxvmFmDbCHVYPsriNpNkLQJKjZB6+FznB7HFTCMo4ki1WLTNVSC25O9J4dzvu8IZuXgK3ibIJrEaeVR6ptlZsfruFwlwjGDkoi9jtlIA/PB7mt4b47+hFoBpl5JFHEkLwSZX2qeVyyuwzk7Q3UfpWfDmfYpWGkavsIlEp8MYJVg2WUvnw5GU6jzzXPwsk2ysPo+pSx3ExblT7fso1JJb7ILjduxjd8K6eFlz6/+l2yb9Waukc0CnIzzFdW2gjaBsXJJB75qeHl2NsnSpq8YVdNtnt4i2WWRg3pnoc4GM+dWd38MUc+SB7bX52QyZDpJ4H8tuQd2ARg4yPOpOOcpWTefvXqdUTGoiFuvSiJOH57S6kklglWXljHh+JIz/CjUN2ikqhwFAUQ6qgqwFFEFUOoFqhw7VUOFEc7xjcJy7a2OTgtdOF7/AGH7Pp8ZWXFahnJtaZZrZafb2q9oY1X8wOv8ajSzQFBWb3j865S6QaVDDaex6GoOKOpbNRS2MZWJ5JbYlveWePqqnHTDp1Woy1ENBMtFSA1VPU0U4UU+iFqoKKKAoCgKgdnocd8dKDnYdQ1C3toS7ubiV9j70kcjoT0U4GcjyryxnlEe7lciTW9ZicRcke1MRyrYgkvuznxZ8OMUnVyj7m+U9tqXEkimRoFwgHh2MOZlsY64xirGeoRlkii1PiSUo8kBHvARKrKGI2nqT28xUjPUN2S68+q3OmxlC6ztPGGO1ovD98eZwO2a3eU4+9rc0ppqnEdsscTQmRVVzK8gOcgt03dsKAME96x4mpCbskVzrur3Gk3fsyPNK6OlrNDGw6+Z88EeVZy1cpxmknOaS/WXELDliJ0SMxAvsO8js2fn3yKu/NblPBf8QSGOPlcsnpMWjP2WO3XPj3DzrUZ5rcr9zrFtY6fb3WotyWm5cYjAJYyydNiL3JzXpxuYbtymvcb8H8J65qcl/PcXWryRRu8CjOyHICQR5wo77z610nDLZu8l0ojPU2R9Uo7v6bOBreaCMSTSiWRo3kROke1Q25s9SpzgY86uWjlExH8y6dZRlMTxh3Oi+mjgV2lzNMkcfKxIU94zeQA6/Z/ezVjQynKcfOGMsojTjPyydFwvxPYcS6OuraekiWzSywqJcbiYW2E9M9D5VxiXbU09k1KXV7mXEen2xxeXuVVv83GP2kn5DoPjXLVy/hjvLhnPkuW9vDbQR28I2xRKFQfAV0xioqGog8nzP51Rm6zr9hpekTapIfaLaEoGFuVZvtHCDHXHdqortxnwqsMk51KLkwsElfxYBPby7dD4u1A284z4dtpVh9p5sjSNFhAcBlUucsRtxgd6UJ5eKeHYljZ7+IJLt2MMkYf3eoBxn40FSz454ZuY1k9rEKu6xR83IJZvVe6j4t0oNLT9Z0rUucLC5W4Nu2ybbnwn8wPTuKC5RTTUDSaIYaCNj1oiJzUGVrd21vYty2CTzHkxMTjaW7t/ZXLURqcG6ctrpCy7ChusOit7whUbYgf7PiPxNVpvUUAVQtRC1QtEFULRAO1UOFA7zqoUd6ofRHIvydX4q2Ab4rZgXfqPDanOPiDO3+zWmXXVGhQFBWf3jXKW4JUVyHF+mEXQuEOyG/2xSSeUV1H1t5fk3un8qJI0u+9stFlZdkykx3MXmkqdHU/nURoIaKlBoH1VPzming0U6qgoCgKAqAqgop2c4z3HaohNibxIVBdegYjqB86UKGnTy313Lfhz7EPsbRfJ8HxS/meg+FcsJ3Tu8vL/ALYjmbaWTXVsZNAucjaeoPcUAm1F2xjYo7KvQUKLuqgLgKWOcKCcDr29BUGXY3Ru7FNU1SyW0Nu0k9ukvikijA99vwuV7gdqspEW8Y460DVNb1e+4hhLXGlXbRxW06pI22Btu3IA91T1Jr0RrYbNsxLn8JrxrbscoiWLe8Bah7da2i3Md2sm+d72ESvAhAC+JwMZfsBXTLqMJmJr6WdLo+oxwz+aI3eXqbDwfcSTXFpaXcVy8VxHbvbw8xm5oXeGPTwqoOMmnxOEZbqm5Zy6DqfDjGco2xzD1f6PdNvtD4c+oruY2N7NcyzWj43IN2GbO/Hds5rx6tT9PD07dWYvOd0+zp9Jivl1C6fUIv55IBtuI/2PJXsiZ6jr1INefSibnd3c8fdFccWacLhrTTkfVr1Dh4bPxqh9JJf2afrXp2tbkJ03iTVTnVLsaZZEYOnWBzKw/wBbct1/JB+dW4OTbTgLhi04fl0G1t2isJ3Ek21zzGZXDgljnzFScrIijL/gDh++tUtpfaFijh9mxHJjdF4vC3T981LU9uBtHZFjaa7MUbboY+d4Yx1yiDHutu60sRz/AEe8NS7gqzQo80k7xxSEKTKQSuOuFyvQClgX6PuH0MhVrj7bpN9r78f+abp7nTtQa+n6RZWDu1uGBeNIjuOfDFnb/vGguGoptEMJoGE0EbHrURCx60RzyQHXdeSDdmyi3JtHflqft5c/vnES/nVIeg9MdOgHYVGiVpTqBaIWiCqFogHeqHUC1Q4VUOFEUtavZLPTpJIgDcNiO3U9uY/RfyHc1YSWdwfabLA3OPBNhbfOSTCnuuc+chJc/OrJDfqKKAoK79z865S2bUVXv7KC+sprScZimXa2O49CPiD1qjgxNcaZfyPdnDRlYNV9D5QXY/dYdG9PyrLLoVOKCdTRTxRTwcVQ+inA0U6iMqTiXTI9RfT3LC6S4httnTq0671Yfugd66eHNWzv5pVj4xs57cXFpaT3EXtBtWK8tdrjsTuYeFh1B9KvhSm9LJxfoixWkySGa3u5FiE6e6hZggL5x0y3lU8KTfBn8sNPMsqxQTzQwDfPcxhCiLzDHuwWDEZHkO1XwpN6T+Velma8gjEks9nPHbGNAMySSnC8vr2z0JNTw5XfCzb63ZS3UdlJvttQkUuLKYfaBVON3hyuDjoc1Jwnv5LGSpf6o1zImkbHs7i5YpK0nQcke8Y37MXHQedePPUv5e0yxllfDbjWOONIowFjjAVFHYAdhXpqnQ4UC5ohaAoEZgqlmICqMsT0AA7k0FAQXlxqkN6l4PqtIvsreL+lkfu8jeage6BVRY1GxttQsLixu05ltdRtFMnbKsMHtUbxymJuGOvDmpwad9V2epcnTli5EaFPEkeNuAfgKOviRM3McuPnsdU4Q1bT7HTLyWXTorZo0ilQEyySsMsT2Zlx6Vx1NWcZji7TV6qJ748y0tW4G1i+1WLF3yIJHjubm9gCo++I7ghXuckCtfPv/pXHqJie3y019S4TvdYe0XWNSaW1s51uORENnNKHIWQ/hz3FdFx1Yx+mO7R4kt7q804wQWUeoCRxz7eWdrZSo6+8obPX7tah5pZ9tf8AEdjAltb8KRxWydFitbyBUHyBVavHqnK1/KG9Ufb6BqKn/VCCb/dkqUtjhniT68tZp206704xOy4u49gdQejofPIpMURNs7Utf1CdrYezTafpk0ymK4BL3t0IzuMcVqillDY6sx92orV03VbmfUJYr2M2sl0DNp9g64mS2jwrSTYzt3uegNBYt9a0m4vpbCC6je8h3CSDPiBT3u/p50Fz06jr1HXv8qgQkAE7hgdScjoPWiq7XtoLcXLTotuwUiUsAviOF/U9qByyxyIHRgUIznPl60QhNBGxqIic0Rnar7Y9o8dn0lk8Jk7lE+8yj7zY90etBrcLaOunafvePl3NwFLr5oij7OPP7o7/ABzVapsUU4CqCohRVC1UFELQKKocKoWiHDvVQ6g4/WS+ta3Hpyg+zRFk3A/DFxL/AGQeUPix9K1DMuuRFRFRBhVGFHwFRo6gKAoK7+8fnXKWzaKSoMjWtES+kiuEIWeMNG+RlZYXHiib/EelBmW8SW8SQICEiGxVJyQB5dayytI1USqaKeDVVyXFnE2u6VqstvZIJIZrHbZgx7tt85blsx802qcj4VYFI8fa5Fbzg2Yk9mto5ZrnqrF5lbGxMbcKUz1oW7LRdTur+GR7jT59PMbbFFwYzzRj9onLZvCfjg1FF1w/pt17SZA4a6kSaVkbad8actdp8vDW4zmGZwZesQ8H8Mae2pXubGx3QRvyt2N6ArEdq/ew2CaZas+belo7prFj20nCj6VYT6Bcie51e5Qaa97Lt8cD/tCjYJVCvugeKtxnllz5Maml4c7Z7qGnXOkycVXOjR38+tXEJYalGn81kASTc/NXCxSortnoR09axGt5OmfS5RG6e0tjUJfo7sNDOtNebbG3k9mfULVy8nOaTeCzLklw4yCa1nnlj3Y0tHxJrHmVuwi4O5mi6suoOZb5d2mNczndcGTLb2VupbqfhSMsso47JlhGGVT3Wl4u4T1DiF+FzMJtVhLF7Z4zhTENxO8jHQVwmp4d8tDLbun6Wtp+q6bqSSSWF1HdJC5ikaJtwV17iumWMx3cYyiey3tf0rLQz60QZqhfzqDIkl03iGPUNMIlezt5FiuZlOxJHXxNEGHVgOz/AKVrsz3ayqiIqIAiKMKi9AAOwArLRfzoDNA0hCQSoJXquRnB+FUGTUEV3cez2stxtMnKUsEXqWPkB8zUyyqLSZZGn3N3pdtjVLd/tGMs15DmVNz9fEo8S47elefDKcI+aP7ucTXdtQTwXEYlgkWWM9nQ5H8K9ETE9nSz6qs7V9Q1G32+zpCkARpLm/u32QRAdAOniLE1UY2jie+try30+8J3vzbniAIcvcTEc1bUP2CxqFBHQfOg3dO0fT9OeV7ZGM0+OfcSu0sr7ewZ3ycD07UHOaxwNeaoksL3620Anurq1eAMswkuhjDt+FQSMDvSymHP9Hetc/6vSUSWU6faajJIzNb+Fw0UIJDbWL5NWymjd/RzcyaxPfRX6JaOnLj04huQVDKVWRQew21LEEn0aXLzbpNQR4liijSDa3LzFy9uV9AY+9LRJH9HUoli598kkcbl5G2tzJg23MMhzgxrt8IpY6XR9POm6Vb2Jk5vs4YB/gWJA6+gOKgsM1QU7++htIedKTgsERF6szscBVHmTRGrosMTxC8DBw+eWQcjocH+IosNOq0UCqHVEAqhaqCgU0QCqHCgWqh1UPxRGRxHqxsbMpE6rdTBhGzHoigeOU/BB+pwKsJKHhTSVs7P2lkdJ7kL4ZTl1iX3Fb945LN8TVmSG7UUUBQFBXb3j865y2SoG0UEUVz3FEMsVv7VEjGLqLx4v2kaEdJUHntPf4VKSYZelak7uLO7ZfbFXdHKnuXEXlLH/wDcPKoyXiHVbzTrGOa1VN0kyxyTSK8kcKEHMjpH42HTHSrAwrTiPjQzNF7NDKLhnktZGjmXYiSBeW/bO4HKdvjRTRxjxhIjezWdrMUUSNKYbhUySgMGCc74y5y3Y4q0FfjfiyMSg6bAZ4gycjlT+PaD/Og3VRFkY2HxUpT4+N+KZVjMVhGZJE/YtDcK3UH+cZ6rywwC7e/WhaG74643s4ftNMgldgWWVI5xGuySSPYwJyTIYwVx2z50Vm/TXrxu+DxYR2+H5ts18xPSKYjf7On43A6t6Cs5YTMcPR0urjp53lNQ8ai5ojtQXbcoHL7/AGfj/wBnr1r7PSTWnETw+P8AiWpjlrTOOVxLVifGs8QuL5svC/Lugx/nB3LuXd57utfP6fCY1rmOH1et6rTnpYxjKN3CtFIv8ltaiMxVpHtOTZ9ftGEhJYL57Vr0/iEbsYrmXi/B9fDDVvKaii6oW26ftuWuAtlb7OrHknb1j/d2sK79JxpxE8PN1+pjlrZTE3EytTuG4s1CWLUGx7K4W/3H7V+UMpu/ePSvnaWExrXMcW+vr9Vpz0eyMo3VDpvoa1fTtK128utQvfZLb2bakDZHOkZvCAvmw8q9vW84vjdJlG7u9Ql0K/unklt45bdbm/hlUTO522xi8YZA46b+4rxRnH6PdOLrbaHk28cOc8tQuRny+eTXF1SUFLUX1YT2cNjGuySTN5cye7HEvUgL3LP2HpQXAqr0UBR3wPjUC1QUBQFAUBQKKChNo1o0pnty1ncnvNB4c/1l91v0rlOlHeOJY2o/atWs+l7CLyD/AEq2GHA/fhP/ANtZ3ZY9+Y9Y/wCi5hLnSNXiQeC6SGRZREfuunulkPp8RXTHOMuyxNrxYnvWlJRSZoG0DSaIYTQMJoiNm6VBVvLuC2ge4nfZEnvN/gAPMnyFEY+nWN5r+pmSYGK3i6P/AKiM/wBGP9fIPeP3F6d6pDuooo4oliiURxRgKiDsAOwo2kAqhaiFxVC1UFAtEGKocKBaoUVUPAoiG8u4LO2kuZ22xRjLeZ+AA8yT0FUcvpdpNrerSX16oaCFvGhHQMhyluPURnxOfN/lWmXX1loUBQFAUFdveNYbJWQlFJUCEUVxnEHDqWameBSNNV+aBCPtbKU/00P+r6+Nf+FVmYJpmqSPKLS72rdEboZU/ZXEf44j/vL3HyrKNZZKCUOaKeHqqcrnyOaDO1jU7tJItL0wj62vBlHbqtvEPeuHH7vZR5mg4vjKx0C7s7bhi1mm9q0+fnTSBdzM8ituaRvNmJzXTT1Zwm11Oh8XD5uIcLxLwfqWh6Quo+w3t4u4LJHGgBXd2Pn0x8K6ZddlHk56f4Jo5zW6m9afR1wr9V290NWuy020taiJOYjONxDA47etajrMnCfwaLq3NafoVjqusXcUEd/Dpdj4Y7y5jSPmzA9ceWNvUCnxuT0ZfgOnjj9XMtx+E+B4LZrm/wBbuLCIIXRp1iG8j7i9fe9BT4zJx/4P0uWVLw5pYutNsNLi1PULvVE578uOMx2wfsJH7E+uKzPXZRNU6f8ABYVMzlVfq6PR/o61Gy1qxvkSeX2aeOWBZIwFZkPi3fhApn1WUxRh+G6OGW6J7PTtO4ittQ1CW0SJkZNxVmI8W04PTyrzvVlp1FtWjmq3N3DzjYR3Cx6jNE0kCkbiAOnMK+gPrVQmlaeNPsIrXnPcOmTJPKdzu7HLMfmfLypJELdAUBQFAUBQFACgXNEJmoKd5pVldOJXUx3K+5cxHZKP7Q7/AJ1jLTifuk42gLa3Z9cDU4B6YjuAP9x/4Vn58f6o/VOY901pqtjdttifEo96GQbJB81PWtY6kZNRlErROK2GFqBpNAxmoiNmqCpeX0FrA087bY1/M5PYAeZPkKIx7Oz1DXdQVm+wS2O7b7wts+Z+69yR2HZPnVHcWlnbWdsltbJshTsPie5J8yT3NVtOBQLUQuKoWqgoFohaoXFAtUKKqHAUQO6Ihd2CooyzHoAB3JNUchc3V1xBqUUVoxW2jO+Jx05af6S4Pdn7Qr/b9K0y6u0tYLS2jtoF2wxLtQfAVlpNQFAUBQFBXbua5tEooqBKKSoEIorlNZ4V273sIubaSNvlsFba0b/561b7h8yvaiTB1slxDEIbiQzTJ0aRgFY+hIHTNRlaV6DD1HTNbnvrmW2uNtrJNbOtvgeMRjxnfnK/KsTEvbp6uEYxcc1LJ0vR+LrG122u6ORuRzCSighExMMZbJP3X9e9SIl6dTW0cp59/wD06G6Wy0WzvbwmabUNSbYrZDXMsrjbDDH5AJ5eQ7mur5bkODtJuuCTcJfJLqVxcTbpL6f30LL0HM6qRmsY40+hrZ+NVcezrG420iSAKEkd5sxmE4A/fG7t0rbz/D5OJ0+LXDI17qmlLbWTT/zJhMZOZCn3fUZHrWIvzezKce0Ty6DSPpU4a1a/ntbOInSNPiAmlaPBSfdgIEP3VA71q3HPo88Yue8qvFi8M8QwpYDR0nkaVJd8i7TuY4Gzb5kdTSV0d+HNquuRcZ8IQomh6dJqLX0RtmuLQ5W1AxtbYfwjOPKjWnOnqfVNV+rqbLjfTlgWK5ExlhiXc/SQsAMFmIx1yOtV58tCXKa3d8WaxxXY/wAl9PFvbSKntuq7lLQDcfHt7Z2+R71Hp04wxwnfP9nomqah9W2HNEUl5PlIYYUHjlkboM+S57k9hWofOmU0VlbR3El4IVS9uFQXEo6sdg6Ln0FBYoCgKAoCgKAoCgKAoEzQJmoEzQVryys7sYuIhIR7r9mHyYdRWcsIy7szFqXI1e0/yeb22AdoLg4lHwWXz/tVz2549uY9/wDtmpg+DWLSSQQSbra6P9BMNpP9U+635VcdWO3aV3LTGuqo2eoKdxqFtFPFA7/bz/soh1YgdzgdlHqaI0INIFxGfashGHhA6N8wfI0WIaVpaW9pbpbW0Yihj6Kg/ifiT5mtNLAFQFELVC1UFAtEFURXl0lpZXF24Jjt43lYDuQiljj9KsRcpMucg+kTSprSS7W3lMMMEdzKoMZlCyorjEQO89JBXWdGbY8RffjHRVMXiZkmuFtlkGNviUNzCfwDeAT61PDld5dK4w07UdVbTokYSgzAHcjfsG2PuVSWTr23DrVy05iLSM2+SoBJOAOpJrm05HU9SuNZuUsrNA1s/iijfOJtpwZpfS3XyH9Ienat0zLo9L0yLT7blKxllY7p539+Rz3Y4/gPIVlpcoCgKAoCgKCA9zWJaNqApKioEqKSqEIqKqXtktxGxUDngfZsegz5A/ChTi+fqtndshjdpid0ulzMN/xe0l91189p/hRhrWOpWt4haB8lf2kbeF0Po6nqKgg1LU72K7hs7PkJLJFJO0t0SE2xkDYMY6nPfyFZmXo0sImLm+9cMscRadLrFtevBPcXBza6eqFDEHDbZ3j6g/Dc3cdqb3T4OfXs19F4g07X4LgRRPyoWCuk6+Fg3UEDtVxytjW0MtKrWryy0TlP7Xbw8u42wPuX3t52qvT1Napx3z6qmmRS2d57HaaglxpsPge0uussJB2hYpfPB6bW/WrSWtPaaTNBK9jFY+0uZGjlKJt5o6M746tgjrSmvEn1SaJp1npmnw20Uiys2Wecld0sh6uw/wCQ7CobraCSAjcjAg+YORRFefTdNuGVpraN2Q7l6ef5UajKYTRQ2lsCsUaQK7ZIQBMsf8TRJVtKTVlW4l1ORObNKTFbx9UhiHRV3d2JHUmrLML1QFUFAUBQFQFVSVAUCZoDNAmaIbuoGk0Dd1A0tREFzDb3MRiuI1lj/CwzWcsYnuks57S7tFLWVz9kvX2e5O5MfB/eWuWyY+mf7SzXox7njFCBEq+xEkob2Yb4SR0xb7f2zenYVqNT+biTc29E4Ud/51qO4JLhjCzbppcdVNxIvTHpGvQV1biHWAVWjqIKgWqFqoKBaIKo57ifjK30OWO2EBubqQbyudqqvqT16mvPrdRGH3YyzpZ0bWLHibRrgbGiDq1vdQ58S71wcH4g9DXXQ1oyi4WJ3QmseFtIstO+r4YzyNsSlmOXIhVVXxd+0YrvOczNm2Ff+QXC7G432YkW5aRyjncqPKQXaMH3DlR2rXi5M7IWrbQNF0to71ByXtUkD3DNgskh3vzW+8N3UZ7Vmc5laZGpajda1MtnbQlraTBjtm8POQ/01x95IB5L7z/KiOh0rSorCJuvMuZsNc3B6F2AwOnkoHRVHYVGl6gKAoCgKAoCggcdTWGiVAlFFKBUCUUlAhH61FVb/TrO/gMF5EJU7jyZT5MrDqp+IqjldW4cvrYi4XmXgh9y9gwL6NR+Ie7OvqO/wqM0oi8iuYUOpW0Wp2it0u4Y92xs4+1gPjQ+uKlLjnlj2mm3HZWCSmZLaJZSQxkCjOR2P5VF8TLtfCa2gtbdWW3iSEOdzhBjLepqk5zPdFq2nRanZC0lOI+bFI3xEbhsdMEZxWscqYmLYV1wIjO5tbs26l98QwX2eMv5k597HWusa7M4HS8DcwSxi5RUlffvEeJF6sdqkHorb/EPOrGseGdJwKhv/aUutsQ3bbcAhUBz0TBGO/Wp43B4bZ4c0p9I0xbJ5/aNrMwfGMA+Xxx6msamW6bbxioaUs0MMTzTOI4Y1LyO3QBR3JNYaZ8MFjrEmn6yDK0MKtJZwyAou5+gmKHru2+7mr2Tu1M1FGaKXdRBmijNUG6oE3UBmgTJogoE3UQm6gTNA0t0oGlqIYWqBhegiL0RjnR9b1W7aOdN0ER91wY7RT3GV9+4bH9mqU6fTeHrG0BZx7XcuNsk8wB8P4EX3UQegpLVD6ja1YyaTcG0z71q32luf7B6r/ZNcvCr6eP8MbfQHWpbQ7dXtjbL2F3HmS3/ADI8Sf2hU8Wvq49/I3V3akUkcqCSJ1kjbs6nI/UV2jlu1bUtTt9PSJ5gTzZBGAvfr3b5KO9ZzzjFmcqUn4ntknkiaFjh2iiKlWLupC4x3XJPQmsePFs7yXPEqWpCXFs0cwYiSIunTADdD2bIPTFMteu8E5pTxDAHuBysiA7Bh1Ls+4KBs7jJPnV8aPyNyY6rJG9ulxZyQmaXk5LIQGPbqD4s1rxPWDci/lLY+yT3KqxEMpi2dMtgZ3D4EA1nx4q/Q3sDWuHv5VONRsnW3uIvsJkc7kYDqCHXPbNcdTS8bmOJhiY3N3hLhsaFYvE8nOuJ23zOPd6dAB8q9Gho+HjTWONMQfR5rMXF767bcSXZhaJ1itrnE4hdyPcVvDtx+fxr02lNuOfVtJzLrOpw3VrjCIkBjnaTyCKrNu+QFRXjWufTnf2XE15o3E+nbI7GbEHJwyrk5WWeLJ5jKh6IDjNemNG4uHGdTnl7JwPfaFqWgw6po0ktxbXhLtd3Css0rZ6s+8KT8PL0rhlFS7YugrKigKAoCgKAoCghbuaw0aRQFQJRRSgVAlFJUBRTcEGgoXWiaZc3S3bRbLpf6aMlGb4Pj3h86FKl3p81ujypmWNBkhRl8fLzqM0wLXWrlgzGNbyEHrLaftEHpLA3jU49KI0rLU7K8GbaZZCPeTs4+anDCgth6KeHoHbqBc1VUBLc3l/eWdxZr9VRqqcyXqZpD1O1e3LA9fOqjRGO1RS5NAbqBd/woDcfSijcfSgN1EG6gTcaAzQNzQJuoELUDd1RDS9BHJMqIXchEX3nY4A+ZNEZU+vwEMbNDdhc7pQRHAv9aV8L+maCrDb6xrDnbulhz0WLdb2g6/emb7SX+yMVaKdnY2AghTmhXuQPtHUHbn90HJAo1S5j1qqWiFoDHTr1HmKIoDRLKO5W4td9o+7dIsJwj/Bk92ufhRdxwztT3em2N46tcwiUqrIu7sA/fHx+Nbywie6zDN1afhbQdN2anKlta3DYXdlpHfv4cZckYz8KzsxiPZmoJptvw1rdiLuwuDeQMzq8yyNvLEAMkmevYdjU8LGTbC/9R6fiRcPy5fej3nbn1A8iMdK14UG0HQbBgN3NbruYmRssfVvXGOlPCg2lXh/SV9yDYDHyiFJAK4x1+PXvTwcTbCzZafb2avyt2ZCGd3O4kgYHX5VvHCIIhaArYyNT4gjgMsFmFmuIf8okc7YIB+KZ/wD7R1q0lsmw0q/1KcXjSOiN72pSDbcSI33bVP8Ao8Z9feNaRzPEX0F6Prf0gWmuT7U0OC2UXNguQ088bHbuP4SPe8zXTHWrGmZ07l0ukahrMtjvjPJgtrXcixxoE3DftXb3x4R0Wvl6ernlF+xEyuW3EWpIbhbq0kkkt4o94jXwb9pYtu/C38K6Rr5ecLua2k6i19BJIVUbJDHlCWVsY8QJA6da7aee5qJXq6KKAoCgKAoImrLRKgbigTNQFAUUVAlAUUlQBFFNwaDP1DQtKv3Es8OLlfcuojy5l/trgn5HNCmHqHCN6xUq0WohMbTcfYXK4/DPH559RRmmU1zqdgQk0stq3U8jU496dewFzFlT+tEb0cjFQW6NjxAds/CoEXULQzNBz056Y3x7huGe3ShZbuI3Ns0Imkt9+PtYjh+hzgH49qCyHopd9Au+ijdVC7qBd1AbqBN1AbqBN1Am8VEJvoGl6CKa6hhGZZFiHq5A/wAaIpxa3YTzLFbu05brzI0YxgepfG2gupFcS9I0J/eoMqHhTVLxg94m3BbD37Cdh1+7bx/Yjp2yTVWm9bcLabG6y3O6+mTqjXHVF/qRDCD9Kq02cVFFEFAuKoWqgoDFAtEecfSjpOptqtjq8NrJd2Udu1vLyVMjwsX3btg67W7EivL1ellnHDnqY2sfRZo2qWb6rq14j2Vnf8lbe0mGxiYgd1wynqu7cFGfIVvpdOcMKkwioeg+We49a9LoWgcBVRBeX9nYxCS7lEak4Qd2Y+iqOrH4Cqjn77V7+8f2dUlt9/uafFj2yRT2aRvdt0Px61Yhlc03hpE5Ul8I25PW2sYhi3iP4sHrJJ++1LWm9UUUBigKAxQFAUBQFAUBQRmsqSikqBuKAqAoEooqUCgSgKKSgMCopCtA0jI2sMqfI9RQQSWNpJ70Yz6jpQpgahwneS84xXMF0kjeG3vYB4VP3BJHhsDyyKM0z5NB1W2ctFaXEQRfC1jch1Pp9jL/AAolKkup6np9qGursp5B9RtHi6nyZ4Mrn5Cg1rC/e4RmZoSRjrBJvH5+Y/OoJLq+NvGr8mWfLbSsK7yP3iMjpQRfXtqF3Mk6jz3QS9P4UFduMeGlmED6jGkx7RsHB/itWi1uPXdJfAS8iO73fFjP61Bc5lBmXvFPD9ixS7v4oXBwVO4nPp0BqlnRcR6ZOA1vI84bs0cUjD/dqBG1vxARWV3N1wSsJUD57yvSgswXUsgbmQtDjsHKkn9KCO9muliBtzg56nlPMcfBUoM6LTuIb1XLi+lVm8KNy7BAPhjdIV+fWqtL0PBl00rO3strlAvM2tdTf3pTt6eVCmvZ8L2ELI88k15KmMNM/gyPMRJtQfpVWmxtqKXFUFRC1QYoFogqgoFogoFxVEUt5aQK7zXEcSxY5pZgNu7tuz2zVpFee80O9ge1mureWG5ifenMXxRYwx79h61aHE8I6DfcG2tw2l3Z4m0iSVmniSTfc265OzleIq+F7r0PpWp5Yjhp8YfS3wfwvpMV7cT+0XN1HzLPTo+k8g/eVsGMepatYaU5GWcQdo30h2/EPD1vrOlhbWzl8M1zdn9nL96JI18Ujg9u1ScKmiMrWrDSdRu25+6W35g8eo3ODetnusUfuW6/lmoOhsNOs7GIx2ybd3WRz1dz6ux6sfnUaWqAoCgKAoCgKAoCgKAoCgaRUDcVFJRSYqBDQJigKgTFAUUVKBQJiiioEqgqAwKKTbQGDQGW+NBD7Nb9cRIM9/CBmgrXej6ddoqzRnwtuUozRnOMd1IoUrNwzY4AW4ukI7ETN/xzRKQfyUbmbhrF9t/zRaMr/FM0KP8A5M+IH2+VseTJGf8AhQpc+qLf8bUKUbjhYyuWTVry3BOdsXKH5dUNCkicMWwxzL28mI/FLj/dAoUX+SWisytLHNOy9RzJpT/AEChS9a6Vp9qCLe2SLd3wO/zoq0q47dPlQOx69aoKIKgKBcVQUQtUFAYoFogoFxVC0BigwJtH1ZtW1Uqls+napCqM7s3NR0iKDwbSpGT61u2WFrXC+oEyKzWlnYRW8SNeykr4hbtEyquMFTn1yK3GTMwaYtVsrDV/qWdbdL9FNtrt74OUVj2gBCoMuCPB08+tB8xQcN8acScU3GnC2uL/AF4yH21pc7lOffldvdXzGa9+6Ij2eWpmX0J9G3ATfR5uS7kGoahcrFJdv4hDBvYpiDwkD95mIzXy+o6qd1Vw7Yxtd8vEd37LdSvaLzYE5iwB8HZkjJJABHTuua4ePNTx2b3Lt7qV1HdLb2sSO4i9olMr7F2A4wDg9fnXTLObqFmWZNxXdRm4/mqkKcW53N4sSiM58PX3s+HNccuomPJNzQTVb4NbJJa5edZSShIGYxkKA4Vsn4118SeOFtc0+6a6sobhk5bSLkpnOD6ZrphlcWsLNaUUBQFAUBQFAUBQFQNxQNxRRUCYopMVAmKBKgKBMUBRRSgVAUCYoCooqhKgKAoCqDpQFAUBioCqCiiogoCqFoDFAUQtUFAUBigWiCgXFULQFAuKop3msabZuI55hzz7tunjlPyRctVpm2Zea7fbE/Z6Skh8PtX2l0w8tlvHnr8zViEtBa6ZfXkvtiwMkx8IvtT+0lC/6q2GEj6+uPjVRs22hWcVwbqcteXhGOfOd2Pgi+6gz6Cpa0uRWdrFNNPFCiTXBBnlVQGcqMDce5wOnWio59MsJ7hbiaBZJkwFcj0OR/GsTpxM2lEi0nTYhKI7ZFE/7UAdx6fKkaePp3KJPpOn3GOfAsu1i67+uCe/5fCk6eM9yjW0TSWMu60jPO/adO/XP+IqeFj6G2E0NjaQiMRRBRFkx/Dd3x861GEQtJo4o4kCRqFReyitRAdQFAUBQFAUBQFAUBQFQJigbRSVAlFJUCUBigbQLmoCgSgKKKUCpQKAoCgTFAYqKMVQYoDFAYqAxRBigKoWgKAqgoCgMUC0QUBVC4oFoFxQV7vUdPs8e1XCQlvdVj4j8l7mtUls+biCRrYz2doxiHUXN2fZYceuX8X+zVpNzO9pu9Rcpz570LnMNgvs9t1HZ7h/E4/qmqi5ZaBfFSXaPS0kwZIbEZlOPx3L+I/kB86WNay0jTrNt8EIEpGGmbxSH5u2WqKuUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAVA3FAbaBNppS2NhpRZOWalFk5bUoscs0osnKalFjlPU2ll5bUoscpqUWTlNSlscp6tFjlPSixynptLHKeptLHKem0scp6bSxynptLHKem0scp6bSxynptLHKem0scp6u0scp6UWOU9KLHKalFl5TVKSxymptLHKarRY5RpRZeWaUWOWaUWNhpRalevrIlEdjbQshGTcTSEAH02KpJ/WtUlqtzputvHLJJetK3eK0t8Wy/Iy+NqCrYcN3sRDx+z6cxYs7RKbmcg+Rnm8/kKqU0IuG9ME4uLhWvblRgS3LGXHn0U+EfkKllNQAAYHYUUtAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFAUBQFB//2Q==


目前已知,HBV感染在生物学上呈现有两大特征:第一,HBV感染细胞后会在细胞核中形成特殊的共价闭合环状DNA(cccDNA),为病毒转录复制的模板,可在宿主细胞中持续性稳定存在,在HBV慢性感染与停药后再发过程中扮演关键角色;第二,感染有HBV的肝细胞除分泌产生完整乙肝病毒颗粒外,还同时分泌大量病毒蛋白,包括乙肝表面抗原(HBsAg)和HBeAg,它们是HBV感染的标志,并具有免疫调节功能、引起免疫耐受或损伤,在形成和维持HBV持续感染中发挥重要作用。

当前临床治疗手段并不靶向或未有效靶向cccDNA,且仅在极小比例的病人中清除表面抗原、产生相应的特异性抗体。深入地揭示HBV感染复制机制,进而开发出新型抗病毒策略和方法,有助于改善临床治疗慢乙肝的效果并对最终治愈慢乙肝起到推动作用。

复旦大学医学分子病毒学教育部/卫计委重点实验室袁正宏教授领衔团队所撰写的文章"New insights into hepatitis B virus biology and implications for novel antiviral strategies" ( http://nsr.oxfordjournals.org/content/2/3/296.full)综述了针对HBV生物学领域关键科学问题的研究进展,并对新型抗HBV策略研究的现状和发展进行了深入的讨论和展望。

该文简要概述了目前人们在分子水平上对HBV入胞、HBV cccDNA的形成代谢及转录调控,HBV核心颗粒形成,HBV DNA逆转录和HBV病毒颗粒的成熟分泌等HBV生活周期中各关键步骤及相关参与因子的认识;此外,还归纳整理了目前HBV研究过程中所采用的各类体外和体内模型的适用范围及优缺点,阐述了HBV研究模型对于推进HBV生物学和治疗策略相关研究所具有的重要意义。基于此,文章进一步介绍了目前针对HBV cccDNA,HBsAg,HBV 核心蛋白(Core),HBV多聚酶蛋白(Pol)和HBV所编码RNAs等不同靶点的各类新型抗病毒策略,并分析了它们各自潜在的抗病毒效果和局限性。

文章最后提出,组合采用多种根据HBV生物学特点所设计出的针对HBV复制各关键环节的抗病毒策略,将可能有效提升综合抗病毒效应并为最终治愈乙肝提供希望。然而,如何联合各种抗病毒方法以使之最大程度发挥出协同效应仍有待进一步探索。(来源:科学网)
页: [1]
查看完整版本: 最新综述:乙肝病毒生物学及新型抗病毒策略研究现状及...