From 67f02ab5092839b04164e053cc7f6ccaba3c2fd7 Mon Sep 17 00:00:00 2001 From: blakeaw Date: Wed, 31 May 2023 13:15:06 -0500 Subject: [PATCH] PKRO example case: notebook and schematic. --- example-notebooks/1_simple-PKRO.ipynb | 344 ++++++++++++++++++ example-notebooks/1_simple-PKRO_schematic.png | Bin 0 -> 50300 bytes 2 files changed, 344 insertions(+) create mode 100644 example-notebooks/1_simple-PKRO.ipynb create mode 100644 example-notebooks/1_simple-PKRO_schematic.png diff --git a/example-notebooks/1_simple-PKRO.ipynb b/example-notebooks/1_simple-PKRO.ipynb new file mode 100644 index 0000000..45d229e --- /dev/null +++ b/example-notebooks/1_simple-PKRO.ipynb @@ -0,0 +1,344 @@ +{ + "cells": [ + { + "cell_type": "markdown", + "id": "527f3a85-4b1f-4d92-80e9-a1d6fe625d89", + "metadata": {}, + "source": [ + "# Simple PKRO model\n", + "\n", + "In this example, we'll use PySB with the `pysb-pkpd` add-on to build the simple semi-mechanistic pharmacokinetic receptor-occupancy (PKRO) model pictured below: " + ] + }, + { + "cell_type": "code", + "execution_count": 1, + "id": "02adb24a-3285-4cab-af25-5c69ab7036dd", + "metadata": {}, + "outputs": [ + { + "data": { + "image/png": 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bQEhks51GeB98G9gn6/7JwD6xwwGEmtSXCf9eJ2cfErgt+z53v9rCamTnsHiP2jnAuRTnHuB0wv+L/xXYbixweLv7rgb+r919RxFacB0XvzLeBvZ19xmFgnH398zsZ8CvCD1sIbz+q4B3aevLC+H310z48HBB1v3zgV8T+uu2txWwWnxcREQkdRZK7BZedr2SRf/YtTcduMDdT4/PGQ08VeSxamI9HxZWoto13j8FWD3XH2kzewHYABjm7h+a2evkbiRfyHh3v8PMrgS+VWC7R4Cv55kwkx3T7sBdWXet6+6v59l2I+A5QieA1ToZd0Uws/G0TdJa1d0nFdh2A0Kf2BbgEXd/2czWBvq4+ws5tl87bj+AkKjd5+6LTUyLrb5GACsR3m8vZtqA5di2D20JWxPwHvDf7A91HTGzJwkrq63l7lPbPbY84fL+a4SWX6MI7b4ed/e8yXAcCd6SOBoNPBC7Q+Ta9xvtfw9mNiq+rlrgYXd/xcxWJdQHv+juzXE7AzYkdKUYQig1eMbdP80T103AfsCIrA8VkiIz603WAiXRHEKJymft3zfxOUsDHV1tAGh190zZTOZ9uXTW407onvEl8EnmnJ/jeGsDK+d46H13fytrux1YdBCmEfgM+Njd5+XYbx2hV7O7+4P5XoSFVfk2Bma6+zNZ99ew+BWNfJ7K/D+zsPx0+9r4GYQ69E9ytPLLy8y2I/w/b3L3Rwpsl/l3bnb3h4vdv0g1MHfPTBp5kvDH/w1C+6QHCSObg4DNgUOBfQmJ2uqwSHI7GfhFoQO5+xULD9qW3L5E+ON+hrv/fLHgFk9uD2LxlkyjgO8SRrLOy3Ho+9z9/azk9lrgzvhYb2CteP9X4j42LNSSysz+QphxP5GQaJ/l7u1H2zLbKrk1248wSgrx3zHNeMrBzMYSLuFf7u7fTjuepJjZ9oQyjD+5+1FpxyNBLCX5IM/D84C/Az/O/r8Y/y0fLmL38929d9bzHiYkk7lMBn4HnBf7OGfHeBG5Jyee7+6nZG2X+RvUXguh3vwn7v581vaDCR9gW929V47nZbbbhVCW9Ky7b5Z1fx9Cr+xibOjuL8bn/Rr4QZ7tZhOuBv3I3WcW2qGZrUX4G5wxIt9VxTifYBLhymCxrQpFqkLmE/FfCIntv4G92436zCGcDP9uZlsQLrm2Nz07ee2E0wmrK51oZhe7++RCG7v7ze3vi7WW3wU+LTKGl9z9luw7zOxiwkjaGoQEPufSqWY2gNA0fxrhcvFjwCFm9vPshvyyiGIWcago7n5//BB0lJnd4e53px1TqZnZEEJpw2csXkoh3cMC2spL6gnn+N0IrfB2MrPR7t4+CZ5C24fRXJrz3P83IDPi2pcwKLEtYaBkDeDIdtv/mXD+PBTYOz7/JuDNPPv/A2EktBcwlDA4siuwrZnt6u6PF4i5q/5E/nkCEH5X7T0JPBq/rydcARlHKKHa1My2cfdCbQUzZX5fAsvGn/X/S6STauMo0zbALODgXJd1M9z9qXhZvlTeJ5y0TiD8Bz6+hPsumrtPNrNHCfWbhcoeDiC0VLre3R83szeAtYHtKG7UoxoV0y2hEh1DmKB1hZnt7u4vpR1QqZhZA+FD6SDgAHdXC7Duab67/zj7jjiyeQ/haty5hLZ42T7yRZeqLta17v6PdscaTxgY+ZaZnZ9dvhVHW5+3tg4pr7cfdGjn3OySptjt4xrCVbQ/AOt3IeaOfLeDRDSXh9z9Z9l3mNk6hCucmxL6R1+b64mxJOhQwiDAMYQPGRo8EemCGsJ/NggJW8GRU4BMbV4JnUVIrI+JNYBpyYwwtl/SNVvmU/UN7W6LmlRXpYrpllBx3H2Wu2/g7itVUmIL4O7z3X2suy/jYREM6SFiDXhmJHBcwsf6B6EWHkJiV8p9LwBOij+uF0sxuqVYVpC5elNoGe9tCZNnH3H3vxHKE1aJ94tIJ9QQ2g9Bx/0yCxlkZkcX+sr3xDjq81vCJZzTliCGLjOzgYSRDIjN/nNsM4wwQvsB4XIawI2ECRQHxFotWVzVlSWIdHOZSbMDY4eQJGVqTDs7Atohd/+MMMEMur5wSrkU83toP3hyY7v7RaRItcDy8fuCXQI6MJQO+oCa2R/zzZwl9CX9LuESzK/d/ZUliKVT4if+ywmv4Q4Pq1nlcijhw8CNmUtE7v6OmT1FmMW+N6EnqSyqWssSRLqrEfH20/YTvYC+VrhHs7v7c8UcJA4arE0YACj51Yt4pa933P/HOR4v9DrWLOIQG5tZvmW+AV7L1bEhRxxG24htzt9D7HyQWcQlU/N8A3AqYfDke8UcS0SCWkLxP4RZtF31BW2N83MqkNjioYftWYQR3DMJk7aS8hMzOzZ+v3T8csKJpNCM70Pj7Q3t7r+BkNwehpLbXKqyLEGkOzKzvrRNCr41xyZrAs8W2MV8QkLZ0XH6EFpL9gX+kW/Gf1fFll2Z3sqP+OILiNRQ+HUUI99AR8aGhMVQ8opx/h+h7dgk8v+N2ItQw36ru0+HhYMnTwNboMETkU6pBaYSRi2X5LLOVM9apKGLLgNOBPY2sy3d/ckl3F8xMonX7e5+aL6N4qSHEYRlYj+OPSEz7ickbbua2XKaXLMYlSWIpKPWzA6M3y9FqN88hDCD/z3Cwh7tTSeu3JdHvn6tPzCzzJLQQwkTvAYTlpJuv1hJV+xuZl8QJvSuSJj8uzlhvkauichO7uQ9YyihzKyQ2yh8zso1P2O/2M4LwlLg6xK6VLwD7FZgglr7koSM6wnJrQZPRDqhlnCSG0poKJ9EO5WiuHujmZ1KaC90NqE5fxLOdvfzAcxsfcLKa/ua2fcz9+eQSXxHED4M5HMwcGHJIq0MKksQSUcfYLH2icAdwDE5RjshLKJwUBeOtXWO+y4ETip01a4TLslx3zPAke7+co7HvNDryOpzW8ghXeiWMIK2so+MR4Bd8+0rttUbR/jb0r5t4M2Edm4aPBHphFpCb9stCF0Tfp9uOFxLaIS9vZklOpMXIK7SdDDhZP9rM3vX3f+evU1c8eZgwif4h3LsBsIn9M0In66V3C5KZQki6ZgP/DJ+P5dQPvaUF1glcAkcQmgxBvB1QkL2LcKS0outLtgF5xL6i88nJIHPlXNuRif8Fjgjfr8JYTXL7Qj1tO1HZTO+BtQRSjheDyW6i6lFgyciRasljJT+ENjazA7KtVBCNjPb2t3/k0Qw7t5iZj8jXA46i0VH/RLh7neb2fcJK+lcb2Y7Zi/HSGgUPoRQ1zUm1z5iHdtkYBMzW9fdX0s67h5EZQki6VhQgnKxYs1x92nx+9/F5WiPBe40sy3c/aMl3P8fEkrKS21e1u/hATM7hrBgxZ/M7AN3fyzHczIlCY0supTxwn0Skt9DUXIrUpQad38buCj+/Oc4krkYM1vRzP5IngbUJfR3wuWmjQj1Solz9wsJHRP6AneY2fCshzMnnhvJw93nArfHH/PW7lap7A8oSm5FqsPxhFHLFYF7YueEquPuVxNGnRuA281s7ezHY33uZsCHwDLuPrj9F2Fp+NmEFc6SWKxCpOJklt/9IbACoTThRjP7CaFc4VPCqOVGhFXM6oC3c+xnFTPraGbqZsXUXrm7x+M/yKKjfkn7HmGixS6E0YZtCJMS9iYsY1locgKE5PdQQjuzn7VbUWaFDn4/d7r7qV2OvHvL/Bu2lqj2TkS6uXgVbgJhTsP6wE1mtlcCiwD1BD8BVgUOAu6OE6YztbNfj7c3ep5VyNx9rpndTvj7MgH4adIBi/R0tRBWHYsjtncCpxDWBR/Zbtt3CDVDV+TYT29CfVFJuPtDZvYvIGcZQBLcvcnMDiK0f1kPuIWw3nlvQv/bQhPJIExO+AIYBmxP+HCQ0UDh30+uCRGVIpPcqt5WpPtbycwK9SxvdvfvFrMjd59pZvsQlp4dR7ik/l0AM9sIWIPQBxdgROzs8Ka7F2yvVUaXmFmh89aviim3iAM23yS0WdsIuM3MxhAGTTIdJm7qYDeFBk/6dPBv9qK7X9pRnCKVJDNym+lDez2h7nR5YC1C371pwHt5/hP/jyJbiLUbtTuAMAo8M8/mEEZMM6t+zSiw3b0xho5GBI4nTFbL28/X3afFk27muC2Ek05jvudkPbfZzFYn/E4zx3iJ4n4/hRqF93SZsgSVJIh0f8sAeVeUJEzoKiq5hYW9WvclrIB5rJm94+6/BY4gXC3L2C9+nU8HvWPL6FsdPH4pUFQtsbvPMbM9gacJV0GvBf5AaM/2urt3NOnuX4R5HZmVMh/Oeqyewv9md8RYRapGba4747KGn3X05HiJaVpH2+V43uwitmmkuKSyqZgYYl3s3FIdN89zZ7X7uaWY2CqcRm5FyusLwlWvzvyfe4nirpS1/5D6fcIkqLwJqbs/bmajCSVurXFhg0sISVd77VfK3Jfwd2pyEbFB6Hs7hlBSVshzcbv2AyzzKf6K4TtZ3/+R0PP8vXwbu/snZrYtYcQaYEo81mKrq+V4bnPsILQsbb+jyUXG+kUR24hUFFMZpCTJzH5OWBFplrsPSDseERERqWw5R24liCMMXyGMOCwbv5YGMklaA23LF0tu28TbejM7J9VIKlcjbaUwswlXC6YAXwKfA59W6UQekcWYWS3hvL4c4Zy+DOG83j9u0ocilhgWSdhcwpUECFcYphHO6V8SRuM/zTcJUTRyC4CZDaZtEt36wGrAcGBlQj2TSE/WTKgNnAS8C7xGuAz9krsXe7lXpEeJc0dGEs7t6xI6FgwnLIergR3p6RYAH9B2Xn+FMDn9pSImwFe8qktu44pjGwFbxa8tCSe7XL4gvHEmE0bCMl/zgDlxm+xRM1ncwYS6uZnAkSnHUomyrx70iV/LxK9lCVcdViGMVOUymTCb/Yn49WysOxfpMcysN7Ap4Zy+NWHVzeXybP4p4bz+BYuf1zPn8uxRM5Fyy7560I/Fz+vLET6oDcnz/I9oO6c/ATxfbVfvqiK5NbNVCa1oxgE70Xb5CcKki7eJI1mETz9vETpEdDgBTQozs7OBHwOT3X35tOOpVvGP/3BCL+eRwCjCVYp1CJ1LMhqBR4D7gHvcfWJ5IxUpjpmNoO28vh2LlhI0AROJI1nx9l1gkj68SaUws36E8/pahPN55ty+BouuEzCbsHbAvcC9PWS1vyVSscltPPEdBBxI6FubMYfQWDzzieap9l0OpHTM7NeEFmyfuPuKaccji4pLR29KGO3aCtgWyF5N6l3gZuBmd3++/BGKtDGzTQjn9AMJ5WMZ04HHaDuv/9fddUVNqpKZDSBcvchcod6aRecHvULo5X9zpQ5gVFRya2bLEVZ8OYxFF6F4DbiH8KnlMXfX5aYyMbPzgZOBD919WNrxSGFxss2WtI2IbZz18NuEXthXufuHKYQnVcjMhgHfJCxisHq82wntvO6NX09V22VXkWLFK3fbEs7puwEjsh5+CbgOuDZr5bwer8cnt2ZmhF5/RxEWfshMAHuVthGnivxk0hOY2QXAicD77j485XCkk8xsOG1XQDaNd7cQenr+kbB6n3oYS0nFD1l7E87rY2lbDOa/hPP6Le7evieuiBTBzNal7by+brx7AfAPwnn9Ae/hyWGPTW7NrIEwQnsSbf840wifQK5090pe0rbHMLOLCCsRvevuq3e0vXRfZrYmYQTtG0Cmfvo9wrKqfypmcRaRQsxsKcLKYCcQagkhTAC7mvAeeyf3M0WkK8xsA8L/uUMJLfEgDA7+Frihp17p7nHJrZn1JyRLJwBD491PAxcDt2qyQPdiZpcAxwJvuftaaccjSy52HNmTsAzrzvHu6YQlPs9XGxrpLDNbBjgF+A5tNd8PEFYyu1MlByLJMrM+wAHAccDm8e7PgN8BF7v7nHzP7Y56THIbJ74cRZh5vzxhGci7gQvd/YE0Y5P8zOwy4NvARHcf0dH20rPET/3HAocTZqvPJiQk57p7tS89LR2II7XHAj8hJLWZS6O/cfdn0oxNpFrFiZsnABMIXRe+BH4D/L6ndJGq6XiTdJlZjZkdSVjH+3eE/m43ACPcfS8ltt1eph2JVlKpQO7+ort47RxCAAAgAElEQVQfQ2hFczmh5v1HwDtmdrKZaREUWYyZ1ZvZKYQm9OcQ+nheBqzu7gcpsRVJj7v/z90PJ7QX+wswmPD/9C0zOyKu3tqtdesAzWx74FlCgfNQQuuKke5+qLu/mWpwUqxMcqtJRxXM3T90928DawNXEZaoPh942cz2SjU46VbMbDyhpu88Qs/xK4G13P1Yd/8o1eBEZCF3n+juEwir/N1GWAzoKuAZM9s21eA60C2TWzMbYmY3AA8TVhN7GtgqfqJ/LdXgpLMy7zElt1XA3Se5+7eADQk1k2sBd5jZXbGlk1QpMxtuZvcAtxOazN8HbODuR6nzgUj35e6vuPsBwDaEjiWbAI+a2XVmtmy60eXW7ZJbMzuM0Jd2AvAJYQbflu7+VKqBSVepLKEKxZPhGGA8oaRod+BVMzu+J1zSktIxs15mdiKhcfw44E1gT3cfp8EKkZ7D3Z8gLA7xDcJks0OB18zskDTjyqXb/JExs+XN7C7gWsL6yZcD67r7DT2931qVU1lCFXP3OwgLqvyaMOHsQuAxM1ut4BOlIpjZ6sDjwAWEeuyzCKO1d6UamIh0ibu3uvs1hIUgrgSWBa43szvNbGjhZ5dPt0huY03eS4TRnTeBHdz92+4+I93IpARUllDl3H2eu/+I0F7mOcJykM+b2dfTjUySZGbfBF4gjPQ8C2zm7v+ndo0iPZ+7T3f3o4CdCKtX7gG8aGZ7pBtZkGpya2YNZnYpcAcwhDBau7G7P5pmXFJSKksQANz9eUKicw5hItHVZnZTbAclFcLMBpjZLcCfCF0QziTMmXgx3chEpNTc/WHCHIsrCRP//2lmF6XdKSe15NbMViRMGPsOoYfaPnG0tkc1CpYOqSxBFnL3Jnf/CWFiwrvAV4FnzWy9dCOTUjCztYEnCc3gPwB2cvefuXtTupGJSFLcfU4cxd0PmEpYaOsJM1slrZhSSW7NbEcgM4rzFLChu/8jjVgkcSpLkMW4+5OEMoX7CB0VnjCzfdONSpaEmR1IKD9YF7iLcF7XVTiRKuHufyd0uMp0VHjazLZLI5ayJ7dmdgThD9oQ4Apge3f/uNxxSNmoLEFycvcpwG6EVQf7A7eZ2ampBiVdYmYnADcB/YBzgb21Qp1I9XH3D4FtgYsIZQoPmtkx5Y6jbMmtBWcRGgADfMvdj3H3BeWKQVKhsgTJy4NzCZez5gK/NLMrzKw25dCkCGZWZ2ZXEVaPnEtIan/s7vowK1Kl3H2+u58AZJLay8zsNDOzcsVQluTWzOqA6wnrh08HdnP3qwo/SyqEyhKkQ7EsaXvgU+AowqSEvulGJYWYWX/gbuAI4GNgW3e/M92oRKS7cPcrCF0UZgG/IEwiLsvAReLJrZk1ALcSFmV4H9jG3R9M+rjSbagsQYri7v8DtiQszToOuM/MBqYbleRiZoMI5WW7ENo4buHuL6QblYh0N+5+P2EC8YfA4cDNMS9MVKLJbRx5uQPYm9C/dlt3fzXJY0q3o7IEKVpchnVbwkTTbYCHuuvyjtXKzJYmJLZbESaQ7eTuH6UblYh0V+7+MuF8/hawL3BPvPKTmMSSWzPrA9wJjAVeJkwc+zCp40m3pbIE6ZQ4EWlX4DFgY+CBmFBJysxsMKGF4+bAI4TEdkqqQYlIt+fuHxBKz14FdgRuN7PeSR0vkeQ2Nu+9jfACXgB2dPfPkjiWdHsqS5BOc/eZhNKEh4ANgHu12EO6zGwAcC8wCngQ2N3dZ6UblYj0FO7+KbAD8CKwM3BrUos9lDy5jcXCfyG0+HkdGKtP9lVNZQnSJe4+FxgPPEEYKbxTk8zSYWb9CL1rNwMeB8bHfx8RkaK5+5eEK/oTCZPNrjezXoWf1XlJjNz+jtDW5x1gF3f/IoFjSM+hsgTpMnefDexOqO3cDvhrEidCyc/MagjdbrYhXInbWytJikhXufvnhMmo7wIHApeW+hglTW7N7IfAd4HJwBh3/6SU+5ceSWUJskTcfQYhwX0H2BP4TboRVZ0LgX0Ik4J30eIMIrKk4uJdY4EvgKPN7ORS7r9kyW1cevFs2hp5v1eqfUuPprIEWWLxCtDuwBTgRDP7XsohVQUzOwk4DvgS2EMlZiJSKu7+DqH0bB5wnpntV6p9lyS5NbORwJ/jj4e5+zOl2K9UBJUlSEm4+5uEEcRG4AIzG5NySBXNzHYCziP8vse7+9sphyQiFcbdnyT0vwW41szWL8V+lzi5jS16/kZYU/zn7v63JY5KKonKEqRk3P1x4GjC++p6M1sp5ZAqkpkNA24i/J6PdfcnUg5JRCqUu98KnE7II/9WisV7lii5jRMNrgPWAP5BKEsQyaayBCkpd78OuAJYDrglqVYy1Sr2nrwNGAJc4u5/7uApIiJL6leEjixrAteYmS3JzpZ05PYkQiuHt4Cvu7sv4f6k8qgsQZJwHPAfYAvgjJRjqTRnA5sSVokr6SQPEZFc3L0VOBR4m1CHe9yS7K/LyW2sizgDmA8cFGc0i7SnsgQpOXdvAg4GpgHfN7OdUw6pIsQ65hOA6cDX3H1ByiGJSJVw9+nAV4EFhAlmo7q6ry4lt/Gy1Y1Ab+D/3P2FrgYgFU9lCZKIuJz38YTz2DVmtkzKIfVoZrYscA1gwHfc/f2UQxKRKuPuzwGnAg3AjWbWpyv76erI7a+AkYS1xS/o4j6kOqgsQRLj7tcTPmivSFhARrruYuArwDXuflPawYhI1TqXsPT6esDPu7ID62yZrJltQqjFmgesF0dPRHIysw+AlYHfuvv3045HKo+ZDQJeIyRmu7n7vSmH1OOY2V7AHcDHwLruPjPlkESkipnZcOBlwgjuZu7+Ymee36mRWzOrJcxSrgV+osRWiqCyBElUrNM6Pv54uZn1TzOensbMBgCXxB+PU2IrImlz90nAL4A64OqYfxats2UJJwIbE2YpX9bJ50p1UlmCJC72SbwdGAb8MuVweppfEa6u3Ozut6cdjIhIdBHwDLAhcGxnnlh0WYKZLUdYW7wfsKG7v9rJIKUKmdnnhH6ZZ7n7/6Udj1QuM1sReIPwSX99d38r5ZC6PTMbAbxIKDNb290/SzkkEZGFzGxD4FlgJrCWu39ZzPM6M3J7BjAQuEyJrXSCyhKkLNz9Y+AcoB44P+VweorfEj4MnKHEVkS6m9iN60pgaeC0Yp9X1Mht7DX2HDCDkDlP6WKcUmXMbBowCDjN3U9NORypcLFtzGvAcGCMuz+QbkTdl5ntBtwNvEOYHDw/5ZBERBZjZkMIlQP9KbJyoNgC3V8RRuBOV2Ir7cUJKd8l90INmR51G5nZ0Vn3LwDmAB+5+5MJhyhVwt3nmdmPgZuAs8zsQa2cuLi4tGVmZbcfKbEVke7K3b8wszOB84DTgf07ek6HI7ex9dd/gU+BNdx9XglilQpjZjcDB3bhqWrdJCUVE7fnCJMQ9nb3f6YcUrdjZvsBtxF+T5vqA4CIdGdx8bC3gRWA0e7+30LbF1NzewZhxZrTldhKAT8ijMZ25o/kP5TYSqnFRO3U+OOZZtblZcYrUUz+fxF//LkSWxHp7ty9kTCnwihiYYeCI7dmtilh1HYSYSat1hmXvMzsXOCHRWzqhER4hLu/l2xUUo1iAvcMsCkavV2Eme0L/A14yt23TDseEZFimFkDofZ2GLCxuz+fb9uORjROibe/VmIrRTgD+JzctbfZDDhHia0kJY5GnhV/PKXQtlUo8/s4M9UoREQ6Ic4NyHTCKbjiad6RWzNbhVDfMBMY5u5zShmkVCYz+zaFF/hoBT4B1tF7SpIUyxFeBdYBtnD3p1MOKXVmthlhRPtNwpWTjj6Iioh0G2bWF/gAGECYB/ZBru0KjdweT+imcJmSEOmEPwKvkH/0tgY4Xu8pSVpM3C6KP56UZizdyA/i7W+V2IpIT+Puc4ErCP25v5dvu5wjt3FW2sfAUoRRWzX3lqKZ2c5Arv6iDjzo7mPKHJJUqfgp/0PCuWxld5+cckipMbPlCSMeMwm/C00QFpEex8xWIMwFmwmsmKuVYb6R2wOAwYTZ7EpspVPc/UHgHhbtnOBAMwU+aYmUWvyUfwPhU/7hKYeTtiMIv4drldiKSE/l7p8AdwHLAPvm2iZfcntkvP1jAnFJdfg+iy65a8Dv3H1iSvFI9cqcx46MXRSqTnzdR8Qf/5RmLCIiJXBlvD0y14OLlSWY2RqEyQbvA6urLku6yswuAY4ljNpOJizdPCvdqKQamdlTwGhgW3d/PO14ys3MdgD+DfzH3bdJORwRkSViZr2A94CVgNXcfVL247lGbg8ijLJdr8RWltCphJoYA05RYispujbefjXVKNKTed3XFtxKRKQHcPcWQsmZEfLWReQauX0RGAWMdPdXyhGkVC4zOwXYhzBippWQJBVmNoTQgu5LYKV4YqwKcYTjE8I8ihXc/YuUQxIRWWJmthFhCfH/ufum2Y/VtNtwbUJiO1GJrZTI74FvKbGVNMWE7lFgeWDblMMpt52A5QidSpTYikhFiCuUTQQ2iSW1C7UvS9gv3v61HIFJ5XP3+e7+RtpxiAA3x9ucs2sr2D7x9pZUoxARKb3b4u0i5/X2ye24eHtn4uGIiJTXXYTJjeM62rDCjCO87rvTDkREpMTuire7Zt+5sObWzAYQ6tGmA8trMpnkY2a/JrTfaAVmxLsbgUzvzFmEnrZL8vjd7p55TKQkzOxlYH3Cso3vpB1P0mKp2UTgeXffOO14RERKKc4pmExYqGfZzMT12qxtxhAafN+rxFbyiW+kw4Gl413LJHSobwJ/TmjfUr3uISS344BLUo6lHHaLt/ekGoWISALcvcXM/gV8DdgRuAMWTW53jLf3lzk26Vl2BobusF49fz0x5LcLmp25C8IVgDmNTnMLtDrMnBc+I81vgsam8PiseU5Lq9Pq4XsIj2Uef/vTFm56Yh7Anii5ldK7D/gBYZJVNSS3Oq+LSKW7j5Dc7kSO5HbrePtYmYOSnmUCwH6b9154R32tUV8bFn4a1Dd7016d3nljk/OPZxuZt8DHmllDrjWjRZbAU4SSmK072rCni6uSbQk0Af9NORwRkaRkFuZZeF6vATCzpYCRwCfu/n4KgUkPYGa9gX0a6ozdNurd4fZd0bvO2GadeoD+wPaJHESqlrvPAV4AhrZvHVOB1gKGEHpAzk07GBGRJLj728CnwIZm1h/auiWMJgyzPZFSbNIz7A0MHLdBAwP6WGIHGTuqIfPtHokdRKrZf+JtpY/ebhVvn0w1ChGR5D1JqEbYHNqS203i7VNpRCQ9xgSAfTdPZtQ2Y+wGDVjInfdK9EBSrZ6Ot5sU3Krny7y+pwtuJSLS8y1yXs8ktxvE25fKHo70CGa2NDBuYF9j55H1iR5r+UE1rL9yLcCqZrZuogeTapQ5z41MNYrkZc7rL6YahYhI8hY5r9dk/4CSW8nvAKBhr016L5w8lqQxbaUJeyZ+MKk2bwDzCUuNV6Q4mWx9Qu/ot1IOR0QkaS/H25Dcmlk9sDbwubtPTi0s6e4mAOw/OtmShIwxqruVhLh7M2Fhg8FmtkLa8SRkZWAQ8Jq7t6QdjIhIktz9Y2AqMMLMamuAVQmLN7yeamTSbcUEYNuhg2oYvWayJQkZGw6vY7kBNQBbm1lSC0VI9cqc79ZKNYrkZF6XzusiUi1eBxqAVWqA4fHO91ILR7q7CUCv/Uf3pldNh9uWRI3BziMbIHTxGFeeo0oVmRRvh6cYQ5KGx1ud10WkWkyKt8MzI7cA6m8r+cSFG/qU9aAqTZAEZZK+4WkGkaDh8VbndRGpFpnz+qo1wCrxh0npxCLdmZmtA2y05vK1jBxW2+H2pbTDevWZyWu7m1ldWQ8ulW5SvF210EY92PB4OynFGEREymlSvB1eA2QmVHyUTizSzR0CsP8W5ZlIlq1fg7HV2nUAA2lrSC9SCh/G20qdUPaVeKvzuohUi8x5fcUaYNn4w5cpBSPd21cBxm9W/uQWYJeRKk2QREyJt8sW3KrnGhJvdV4XkWqROa8vUwNkZqLrJCiLMLMtgDU3Wa2O1ZbrlUoMu26gfreSiKmA03b+qzTLAK3AtLQDEREpk0weu0z2yO2UPBtL9QoTycrU2zaXYcv2Yq0VaiH0rlsztUCkosRetzOo3JHbZYBp7t6adiAiImWy8IpcDdAfaHL3eSkGJN2MmdUCB9XUwPhN00tuAcaqa4IkYzrQp9ImK8aFeRoIybuISFVw99lACzCghnASnJ9uSNIN7QIM3X5EPUMGlKm5bR5jRi1cOELJrZTSgnhbUckt4ZwOOq+LSPVZANTXAPW0neRFMg4G2G90eXvb5rLZ6vUs3a8GYHszG5h2PFIxMslfQ8Gtep7Mp0Gd10Wk2sxHya3kYma9gfENdca4DdP/u9+rBnZavx7CCNuYlMORypE575VnTenyUXIrItVqAdBQA9QCzSkHI93L3sDA4UN6UV/edRvyGquuCVJ6lZrcZv7X6rwuItVmAVCXbjGldFcfGHz6xifN7HbWVN79vCXteGhs8sy3u5mZ3rciIiKSk5IEWYy7P+WwEfDv1z5qZsyvpvg//9eYSiwz5znHXTWDE/48E0Jf0r8B6TTdFRERkW5Pya3k5O6TCfWtp81udD/yDzM45bqZNDV7R08tmcdeX8D2v5zCLU82AnwOjHf377h7U9mCEBERkR5Fya3k5e4t7n4qsBcw7bpH57HnudP4cEqyZQrzm5wzbpvNQRdM45NpLQC3AOu6+z8TPbCIiIj0eEpupUPufjewAfDUC5OaGHvGVH/olWQmYr8wqYmdTp/K7++dgzszgWPc/SB31wp6IiIi0iElt1IUd/8Q2BY4d+rsVptw0TTOuG02LSVa3LO5FX5/7xz2PGeqv/1ZM8C/HNZz9ytKcwQRERGpBkpupWju3uzuPwb2A2b+/t45HHjBND6fsWQZ7lufNrPH2VM547bZNLcwHzgR2NXdPypB2CIiIlJFlNxKp7n7393ZHHj5PxMXMOaMKf7M252f4+UO1z06jzFnTPUXJjUBPO2wgbtf6O7lm7kmC1mwtJl1kw7HUqniYjEiIiWnP2DSJe7+hpmNBi7+bHrrN/c5byo/2bc/x+3aD7OOn//x1BaO//NMHp+4AKAFOBP4lbun31S3uo0B7gOw8A/pwPT42Hxgbvx+FmGRgK48/pS7P5LYK5Ce4i4zux+4wN3LuppaPHedQdv7tBWYER9uBObF75fk8S/cfVZyr0JE8lFyK13m7vOAb5nZI62tXH7GbbN7P/tOExcdMZCBffNnuHc828gp1830GXPdgFeBw939uXLFLQVNAPjKoBrqao2Z4d9o6fnNzrwFJRtM/zewU6l2Jj3WIOAc4BtmdqK731fGY38T2CXhY/wW+H7CxxCRHIwwsvKRu6+cdjDSc5nZRsCtwGqrLdeLK789iPVWXvSz05RZrZxy3Uzufn4+hPfd74Efuvv8sgcsizGzPsBnvetsqVfOH2JL9cn9AWV2o9Pc6uAwY25IeBc0O3Nj8jun0WluhdZWmDkv1GPPbwqrzJ3199lMnd3aBCzn7tNzHqBMzOwJYEtgWJwwWRHMbGXgA+BJd98q7XjyMbP/ARsTzgUG3Amc7O5vJXzceuDTul4M/tspg6mvDYvFQGhDmPkQN7vRaWmFVm/3Po6Pz2pspaUVWlrDtgDzFjiNTc5jry8AeNPd107ytYjIoszsQ2AljdxKSbj78zHBverdz1v23+2sqX7mwUvZYdv1AeDBV+Zz0tUzffKMVgMmAUe4+8PpRSw57AUM2HWDBvIltgD9exshF4FB/Tp3gKffXsAtTzbWAbsCf+1qoFIxMoktwJ7AODO7FPiFu8/I/7QlshsweOeRDWy+Rl0iB9j+1ClM/Lh5LTNby93fTOQgIpKXJpRJybj7TOBA4Mfzm73llOtmctI1Mznx6plMuHA6MbG9EhilxLZbmgCw7+bJzfMZM6oh8+0eiR1EerJa4HjgPTM7wcySWGp7AsB+Cb7Px7a9z/dM7CAikpfKEiQRZrY9cBOwfLxrMnCku9+ZXlSSj5ktDXw6sK81vHL+EOpri5gV2AWz5jkjTvqcphamEkoTOjWB0MyOBo7OumsBMCfP5tmTfHLZHlgOuBGY3e6xuYQJcLk05dg+I3sCXS6ZCUi5zCNMRsqlOT43n2lZ338FeBx4HjiAEGu+diaNsXa+7GJZwka0jdxmayUMvrwAnODuj5bomEsBk/v1tt6vnj/E+tQn8z5/5u0m9jp3KsBD7r5zIgcRkcWoLEES5e6PmNkoQuIwA/i2u3+ZcliS3wFAw16b9E4ssQVYqo8xes16Hp+4YDCwBfCfTu5iJWCTEoc1ocT76y42At7paCPL396kBZhZ4KnTCcl8LnMIHzxyyXTNWJPciS20XVXcAHjYzG4GflCC2uh9gT57bNRAUoktwCar1TG4fw1TZ7dua2aD0q4vF6k2Sm4lMe7+hZnt6u4lWsdMEjQBYP/RybceHTOqIdMCbk86n9y+BzyQ4/7eQJ88z+kFDMhx/wrxeYWStH5AfSdjrBS9gKULPF7osVLJZKBfBXY3sx2WsLNKKEkYne+tUhq9amDnkfWZ+vKxwM2JHlBEFqGyBJEqZ2YrAB8MHVTT6/lzh9Ar4Ur8SV+0MPqnXwK84u4jkz1afkvaLcHMGoC+eR6uAQYWePpA8s956As05HmsnpBw5wyJ0F5raUKLrXeBc7MeH0BIWHPpQ0j0c6kD+ud5DAonuUuRfxBliw72C23lCQ8DJ7r7ix1sn5eZDQE+WWapmtqXfjOE2oTf5//4byNHXzED4Dp3PzzZo4kIqCxBRNpMAHrtP7p34oktwPAhvVh9aC/emdyyvpmt6u7vJX/U0ost7Aq1sZtSrliyxVZg5wCT3f2KNGIoRgc1t5kuCp8CPyUkiEvaaPlrQO2+m/VOPLEF2HH9Bup6QVMLe5hZLy1QI1I+6pYgInH2eLKXarON3UBdE6SgRuA0YA13v7ZEy3HHkoTyrPo7INaXA5n6chEpEyW3IlXMzNYBNlpz+VpGDivfhZwxI5XcymI8ft0CjHD3U909X/eITjGz1YHRqwzpxcarJtPbNhe1vhNJh5Jbkep2CMD+W5RnNCtj9Fr1DAhLNO8Y2zNJdcrM+wB4FtjK3Q9y9/dLfJwJgO23eW/yN4covXEbqt+tSBqU3IpUt68CjN+svMltbQ3suF4DhIlT6gNa3T4HvgGMdvenEjrGVyHZBUpyydSXAyPNbNWyHlykiim5FalSZrYFsOYmq9Wx2nJJLARVWFZpgka1qlMTcBGwlrtfU6K62sXEZcHXGzmslrVXKP8capUmiJSfkluR6lXWCTbtjRlVn+nOsIcVWElAKtZu7n5CXLY7SWWfMJltrJJbkbJTcitShcysFjiopgbGb5pOcjuoXw2brlYHYYnmTVMJQlLj7tM63mrJmFkN8LUag302z9c6OFmqLxcpPyW3ItVpF2Do9iPqGTIgvdPALhrVkmRtD6y0xVr1rLB0+UtvQPXlImlQcitSncqyDGlHsi7Zqu5WknAwlGdZ6UJUXy5SXkpuRaqMmfUGxjfUWXarolSss2Itw5btBbCxma24JPsysxoz27g0kUlPZ2b1wH51vWCPjdJ9n2fVl+8VSyVEJEH6TyZSfcYDA8Zt2MCAPunP44qzyQ3Yvav7MLMdgf8BPyxRWNLz7Q4ss8uoBpbun+6fuqz68uWATVINRqQKKLkVqT4TIP1LtRm7LMElWzNb08xuBx4CNgRaSxia9GyxS0I3eZ+rvlykbJTcilQRMxsMjAPoW5/+qC3ANuvU0a/BAHaOJRMdMrOlzey3wKuEkeiMlgRClB7GzAYAe9bWwPbrpluSkKH6cpHyUXIrUl3mAX8B+OrvpnHpfXNJpnV+8V75sJmGOgPoB+xYaFszqzWzo4E3gZOA9l35ldwKwFCDOc2tcNAF0/hwSvpvixUH96J/b4NQX75C2vGIVDIltyJVxN3nufs3gKNaW5l/2q2zOOKy6cyYW/4Mt6kFzrl9NnueM5Wps1sB7gaez7e9me0CvABcDgzO3N1uM5UlCO7+lsNGwBMvTGpil9On+r9emp9aPE+8sYAdTpvC7EbHwnLDg1ILRqQKKLkVqULufqXDFsDb9zw/n51On8Lz7zWV7fhvftLMHmdP5YK75tDayjzgRGBPd/+s/bZmNsLM7gL+Bawb78537lJyKwC4+0eEPrfnTp/bymEXT+dnN82iqYyDuPObnDNum83+50/jozB6fKvD+u7+WvmiEKk+BjjwkbuvnHYwIlJesTbxSuDA+lrzXxzQ347auW9ix3OH6x+bx8/+OssbF7gBTwGHu/tbOWIbCpwOHEnpPog3EkozAJYilDXMICTF2Y919NxyPNbV5w4EfgK8C5xbpmMuyWMAM9w9sQ8mZjbe4BqHgVuuVc/lRw9k6MBkx3Ze+6iZ4/40g1c/asZgpsMP3P2KRA8qUuXM7ENgJSW3IlXOzAw4HvgNUHvAFr0579AB9G0o7YSzj6a0cPzVM/nPxAUAzcCZwK/cPedYmpmNBS4FViecp7rHDDhJWgswEzjE3e8p1U7NbE3gFmCDZZeq8cuOGmjbjagv1e4Xam6Fy+6fw7m3z/amFgx4APimu39Y8oOJyCKU3IrIIsxsG+CvwAprLF/LVd8ZyNortJ+v1TV3PNvIKdfN9Blz3QgdDg5z97z1tVkx1QHHAmcA/Ys41PPA/TnuryWM1GYbDwwFboyP50ue+wN1eR5rAPINdfcCBhSIdSD5R6T7AaXPvHqWvdz9zlLuMHbjuBA4uqYGTt6jH9/fqz81JfrY9P4XLXzvqhk8/XYTBo0OpwLnJTkqLSJtlNyKyGLMbFngBmBsvwbz3359gO2zWdf7hH45q5VTrpvJPc/Ph3Dp/2Lgh+7eqdk9cXb5OcChmbvybPp7dz++yH0+AWwJDOtJo2px5TuBbPMAACAASURBVK1+eR6uAdYBHick+ge0e3wAIenOpS8hWc+ljvwfLozCE6Qy5R+59AHyvcGudveJBfbbZWZ2uMEfHPqMGdXAxd8awKC+XS9TyJTb/Pyvs3xeKLd5hlBu80bJghaRDim5FZGcYpnCD4GzgJrDtuvD2QcvRV1t54a3Hnh5PiddM9M/n9FqwCTg6+7+6BLGtj3we2AkuUsVLnT3E4vcV49MbjtiZisDHwBPuvtWacfTXZnZusCtwIgVB/fiym8PZONV8w3Q5/f5jFZOvnYmsRtDM3A+8HN3L98MTRGB/2fvvuPkKsv+j3++m7LpCR0LvXeQ3jF06S0qJCAiYMUCCD6K8CAoiD9UkAelCCT0KkXpRXrvVYHQSyC9Zzd7/f64z5DJsrvZzc7MmZ35vl+veU125sw51+xuzl5zn+u+buYlt+6WYGbzieR0YEfBuDH3z2T30yfyzqedm2Y+dWZwzJgpHHTWJLLEdgywTncT2yy2fwNfAY4EJraxiS//WqdkHQs2Ba55f8Jc9vr9xDj/7hld2sdNT85i6xPHF9qMvQxsFhHHO7E1y5eTWzNrU0TcE7Ah8MizbzWx0ykT4u4XO64mePz1Jrb/zfgYc/9MSP0894yIgyNiWgnjas5mna9O6vRQnNA6ubVOi4ipETECOLKpOZp/deVUvn/BZGbM7rjv8+QZwfcvmMzhf5vMpOktAOcBG0fEUxUI28wWwMmtmbUr6xW6DXD6xOktOuisSZxy3TTmtkohC/089/r9BN7+ZK5Is9LXjIibyxjbJxFxOKlf7+PZw05urcsi4ryALYG3r3tsFjueMoHXPmhuc9t7X5rD1r/+NK57bBbA28D2EXFkRHRt2NfMysbJrZl1KBspPR7Yh2DK2bdNZ/8zJzJucsojn32rieEnT+Ds26YTwRTgyIgYERHjKxTfE6QE91Dgw0oc02pP9nu0EXD76x81s8tvJ8Q/npj12fMz5wS/unIq3/zzRD5O5TbXABtExL05hWxm7fCEMjPrNEmrk/6or730sIbYY8N++vu9MwojubcDh0XE+3nG2FmeUGZtkdQL+DXwK6DhsOED2GX9Ro4ePYV3Pp2LYFzA4RFxU86hmlkr7pZgZgtF0kDgXGAUgGBGwLHAuRHRcbFiFXFyax2RtIvg0oDFih6+gXRl4pO84jKz9rlbgpktlIiYHhEHkzoW3BewfkT8X09KbM0WJCJui9SZ41HSEs2HRMS+TmzNql9plh8ys7qTdSw4L+84zMolIt7JeisvHhEf5B2PmXWOk1szM7N2RMQcwImtWQ/isgQzMzMzqxlObs3MzMysZji5NTMzM7Oa4eTWzMzMzGqGk1szMzMzqxlObs3MzMysZji5NTMzM7Oa4eTWzMzMzGqGk1szMzMzqxlObs3MzMysZji5NTMzM7Oa4eTWzMzMzGqGk1szMzMzqxlObs3MzMysZji5NTMzM7Oa4eTWzMzMzGqGk1szMzMzqxlObs3MzMysZji5NTMzM7Oa4eTWzMzMzGqGk1szMzMzqxlObs3MzMysZjQAc4FeeQdiZlZhhfPe3FyjKL3C+/F53czqTS9gbgPQBPTJORgzs0przO5n5xpF6TVl9z6vm1m9aQRmNwBzmHeSNzOrF7Wa3M7J7n1eN7N60wjMKSS3fXMOxsys0grJ35wOt+p5Cu/H53UzqzefjdzOAPpK8iUsM6snA4Bm5l3GrxWzSHW3A/MOxMysUiT1BXoDMxuA8YCARXONysysQiQJWAwYHxGRdzyllL2ficDi2fs0M6sHi2f3nzYAn7Z60Mys1g0jfcL/dEEb9lCfkiaUDc47EDOzCvksue1NGrmFNIphVULSCcDJpPq56dnD05h3CXVidt+d52+NiHdLHrxZ9Suc78Z3uFXPVXxen5JnIGZmFfLZeb03MC77YumcgrG2HQgwbEBDX6Dv9DlBU3MsUuJj/Br4TYn3adYTLJXdj+twq57r4+x+aWBsnoGYmVVI4bz+SW/g7eyL5fOJxVqT9BVg9XWX7cOdJ3y+FHrSjBYAmpphxuxULjh9dtA0N4iAKTPTY7Obgplz5j3fPBci4N3xcznr1ukAu+Pk1urTCtn9W3kGUUbF5/VHcozDzKxSCuf1sb2Zd3JfLp9YrA0HAey7ab82nxw2oPurJl//+CzeGz93I0lLR8RH3d6hWc/y2Ukw1yjKx4MWZlZvls/uxzYw7+S+fJubWkVJagC+3iDYa+Py9WDfYZ2+kJZf/lrZDmJWvZbP7ms1uS28Lw9amFm9+GzQogF4Ewhg1fzisSLbAV/aYrW+fHGR8i0Nv8M6nyXOu5ftIGbVa5Xs/s1coyifN7J7n9fNrF6sTMpn3+odEZMlvQusKGlQREzLObh6dyDAfu2UJJTK1mv0pX9fMXNO7CSpX0TMKusBrUuybhlfpu2uF9OZtwrVQj0fEbW2KldXrUNa7OD1vAMpk9dIywqvm3cgZmblJmkw6Yrc2IiY1jt7/HlgWWAt4LGcYqt72eoa+/TpBV/boLzLwvfrI7Zeoy93PDd7ILAtcHtZD2idJulLwEmkspFyHWMqsEREzC7XMaqVpGVIfW6fjoi5ecdTDhHRLOlVYD1JX4yID/KOycysjNYhLUj2AqQm5mRf7J496eQ2P7sBi+64biPDBpYtr/nMTus2csdzswvHdXJbPb4JNOy1cT92/0ojzXNTtwtI3THmzE3/njw93c+ZG/N1zWjO0rVJ07OuGnPn76oxbvJcpsyMwaQPNXdU7F1Vj3Wy++dzjaL8XgDWI71fJ7dmVsvmO68Xkttns/uNgAsqHZF95kBov0tCqe24biMSRLAncFRFDmqdcSDAj3YZyDrL9l7Qtl02+t8zOfbSKZA+1NRjcrtRdl/rye2zwEjS+/WHVzOrZRtm98/DvMueD2X3W1Y8HANA0hBgt0H9xI7rlrckoWDpYQ2ss0wfgOUkrVWRg1qHJK0ObLDK0r3LktgC7LRe+lAD7FGWA1S/rbL7hzrcqud7OLv3ed3Mat3W2f3DkCW3EfE+8A6wlqRSr4JlnbMf0H/3r/SjXx9V7KA7rte38M96TXSqzUEA+21WvtH7pYc1sPYyvQFWkLRm2Q5UhST1AjYBZjLvilWtepo0aW7zrMWgmVnNkbQYsBrwZmF+QfEJ7yFSMe5mOcRmqc6yYiUJBTvNGyXeraIHtvZ8HWCvjcv7e1B0daDeWsGtAwwFHqv1jhHZZMEnSZPn6upDjJnVlS1I+WvhatV8ye392f32lYzIQNLSwPDFBzew5ep9F7h9Ka23XB+WHtYAaXRn8Yoe3OYjaTNglQ1X7MOKS5avxzHUdXJbOL/d3+FWtcPndTOrdYXz278LDxQnt4UJB7tULBwr+AbQa99N+9G7whcPJRi+diNAL/yzz1vFJhSuv3wflhzSALBFdkmnXuya3d+WaxSV4/O6mdW6wnn9swnSn6VSETGW1Ph7LUnLVjiwepeSmk0qW5JQsKNLE3KX1YKOaGiAvTYq/+9Bg2CHdevrQ42kgaTJZBOBx3MOp1IeBiYD20kakHcwZmalJGkF0kqML0bEO4XHW48TFkYzdsUqQtJKwEbLL9GL9Zfvk0sM263Zl8Y0iW1XSfkEYTsAS227Rl+WGFKZ4fuiJZjr5UPN9kAjcEetLt7QWkQ0A3cB/UhLe5uZ1ZKvZffztTts/Vf0pux+/7KHYwUjAe2/Wb9Ce6aKG9Aotli1D6SJNlstYHMrj6wkoX/FDrjdWn3p21sAX6uTDzWF89rNuUZReYX36/O6mdWawnntpuIHWye39wEfAl+VtGQFgrKsS8I+OZUkFLg0IT+S+gF7NfYRu6xfmR7HAAMbxRarffahZouKHTgHkhqBPUmtseotub0RmA3sky3xbWbW42WT8bcm5a0PFj83X3IbES3ADaQ6vH0rFWC9krQRsNr6y/dh5aXL07C/s4qSqnqbPV8N9gKG7rJeI0P6V3b4vqg0odZ/7ruSkvh/RcSUvIOppIiYRJpoMQzYMedwzMxK5QBSvnp1lr9+pq3ivquz+wPLHZXlO5Gs2JcW7cXqX+oNsJqkVfKOp85UdNnlYjuvVzfJ7Tey+2tyjSI/Pq+bWa1p97zeVnJ7P/AGsLWkNcoZVT3LVgwa0SDYs8wN+ztrp/rtfZqbbEXAnYcOEMPXrvwV42UX78VqX+wNsHqtfqjJWp3tTeoacNMCNq9VNwBTgH0lLZp3MGZm3ZEtVb858CZFizcUfC65jYgALs6+/HY5g6tzXwW+tPiQhor3tm1PHTf2z9MBQOOeG/UrTO6quDpYpe4QUpeESyNiRt7B5CEipgNXkromjMw5HDOz7jqCtCrZ+VneOp/20qqLgGbgEE9AKJu3gOfHTW5h+5PHx6P/zX8l0HFTPitZ2VrS0DxjqSO5lSQU7LDuZ//FazW5PSy7vzDXKPJ3fnZ/eK5RmJl1QzZBeBQpT72krW3aTG4j4n3gn8ASZLP5rbQi4g1gM+Dijye3aN8/TIxzbp/O5z9/lN+UmcGPL5rCYedOAgjSh5umykdSXyR9Edh66WENbLZKfp8hN16pL4sMbADYttY+1EjaAVgTeDIinsk7njxFxJPA08DakobnHY+Z2UI6EFgcuDkiPmxrg44uiP8puz9GyqsDa22LiJkRcShwSEsLs06+dhoHnzOJSTNaFvjaUnn89SZ2/M14rnx4JsA4YO+IOLJeL99W2EFAw36b9qchx/9hvRoo1Pv2ofZm0x+b3Z+ZaxTVo3BePzrXKMzMFkKWjxbOX+2e19tNbiPiPtISlWtTe3/wqkpEjI7UZ/T1O56bzfD/ncAzY8s7cDq7KTjlumns9fsJvPXJXIBrgbUiol4n3OQh95KEglqst5a0Dunc9R7p99tS3e27pNUI18o7GDOzLvoasBbwREQ82N5GC5rKVPiUf1yporK2RcSzwFeAa96fMJc9fz8xzr+7PIOnL7/XzC6/ncDZt00nginAkRFxQER8WpYD2udkMz3XX2Xp3qy9TL49jgG2X6eR3r2AtFpZr5zDKZXjSBMO/hgRLrMBsu/D2aTvy7EL2NzMrNr8PLs/o6ONFpTcXgO8DgyXtG0porL2RcTUiBgBHNnUHM2/unIqP7hwMjNml6YQt7kFzr5tOjudMj5efq8Z4K5Io7XnleQA1hUHAey1ceVWJOvIkP5ik5X6Qqqz3yTncLota2P4DeBT5k2ksuQ8YAJwkKRV8w7GzKwzJG0PbAO8Blzf0bYdJrcR0Qz8Jvvy1JJEZwsUEecFbAm8fe2js9jxlAm89kFzt/b59idz2eeMCZxy3TSa5zIbOB7YOSLeK0XM1mVrAFx4z8y4+8XZeccCwKar9Cn8sxa6JpxEWrnmjIiYmnMsVSUiJpNq1XoDv845HDOzzjoxu//fiJjb0YZqoz3Y/BukS5QvAqsDO0XEnSUJ0RZI0uLApcDOAxoVfzxkiPbu4oIPEXDpAzM54aqpMXNOiFRHfXBEvFaGkK2TshZ7ZwBHNQh+/LWBHLvnIHrl0PO4uQX+/M/pnPnPadE8FwEXRESPbRclaV3gGeATYKWsx6sVkTQIGAssAqwbES/nHJKZWbsk7Qr8C3iJdM7qcOb9ApPbbKdfJ01EeA7YcEEZs5VONjPw58BvgYZR2/Tnd98cTJ9ONPz/eHILP7tkCne9MBtSP7j/B5zg+sPqIWlvwcUBQ7dYrS9/O3woSw6tXIb79idz+dHfJ/PY600IZkUa8TxjQSeOaibpDtJEsp9GxJ8WtH29knQM6QPWvyKiFkbrzawGSepNGrBYG9g/Iq5b4Gs6mdyKtCzvVsAREeEatgqTNFxwRcCS6y3Xhwu+O5RlF29/3s9NT87i2EunxqTpLQJeJo3WPlWxgK3TsmVvrwXWXXxwQ/z18KHaeo3y9r2t1RF9SXsCN5KWEF8rIqqj5qMKZVcPXgRWAb4WEbfmHJKZ2edI+gHwF9Iyu1u1tSLZ517TmeQ22/mGpD+AnwKrZnVbVkGSvgxcDWy+yMCGOOc7Q7T92vNPSBo/tYVjL53CP5+eDWlBhvNJI1juW1vFJPUjzWL/Tq8G4qe7DdTRewwqS//bWh3Rz5K1F4BVgT0i4pacQ6p6kvYFrgNeJV3q69G/A2ZWWyQtAvwHWBTYNFuMZoE6ff0zG/W7DFiSeZPMrIKyyV/bAKdPnN6ig86axCnXTWNudgH5nhfn8NX/HR9ZYvs2MNwLMvQMETErq3M9pKWFWX+4eTqHlGFBj5uenMU2J46PLLF9GdgsIo6vkaTmWFJie4cT286JiOuB+0hzKn6SbzRmZp/zO9JqZBd1NrGFLozcAkhamvQHcSiwTUQ81NUorTQkjRBcGDBo6zX6ssxivbj8wZmFpy8kjdZ6lngPJGl9Uhu+lb+8WC8uOHIoG6zQZ0Ev69DkGcEvLp/CdY/Nghoc0c9aWj1H6t+6QUS8knNIPUbWc/lZoIU0evt6ziGZmSFpc+BBYCKwZkSM6/Rru5LcZgf7DukP46vA+q5py4+k1Ui1mmsDCMYFfCcibs43MusuSUNIH1L279tb8ev9B+nw7Qcs1L7ufWkOP75ocnw8uUWkEf1DI+LeEoabq2xOwF3AcOBXEeG2hV0k6SRSm537SFd8StNc28xsIUhqBJ4G1gQOiYjRXXr9QiS3xX9ITomIE7q0AyspSQOAvwIDge9GxCc5h2Qlkv1fO0rwh4De+2/WjzNGDmFAY+cKcWfOCU69fhoX3DOD7L/5NaTV6CYWHWNZ4OOe/CG1aLLBC6RuLrVQYlFRrf6QHOmFXcwsT5JOI60yeWdE7NTl1y/MB3RJK5EuY/UHtutofV8z6x5JWwFXAV9ceene/P17Q1ntix0v2fvkG0388O+TGTtuLoJPInU5+Uer/Q4GHgNmAvtExDvleg/lImlN4EnSggRbdKUmy+YnaVPSJcDZpA8JPbpzhpn1TJK2A+4GppEqBMZ2dR8L1VAzIt4AfkxaAejybDabmZVB9uFxfeCO1z9qZtffTogbn5jV5rZzmoNTrpvGHr+fwNhxcwH+FbBe68Q2sywwGPgK8FiWRPcY2WjjZaQP2Sc6se2eiHgMOIV0FejyrPuEmVnFSBoGXELKT3+wMIktLOTIbVEQ1wD7A1dHxNcXekdmtkALWtDj1feb+cGFk3nx3WYEUwOOWdDl5WwVvKtIZUbNpJrV08v7TkpD0p+Bo4B/A9t7cZnuy1ak/Ddp+e8zI+LonEMyszqR/Y27FtgXuCIiDlzofXUzuV2UVKe1HHB0RJy50DuzNklaKRspNwNA0vbZgh5LrL98H/56+FBueXoWp/9jWjSl5XMfIhXgd+r3Jlv95RRSfROk0dDDI2Jm+6/Kl6QDSXGOJ3VHeDfnkGqGpBWAp4BhwDci4uqcQzKzOiDp58DpwJvAV7qznkK3ktssmPVJq0b0AXaMiPu6tUP7jKQtgCuANWqlZZOVRjYR7Bpgk14NMLeFwvK5xwNnLcxsd0kHAecBA0hLHe4bEW+VMu5SkLQO8AipHGG3iLgt55BqjqQdgVtJ9dibRcRLOYdkZjVM0nDgdtIVxC0j4unu7K/bi9hHxLPAj0gTOq6UtHx392mfXR48h1QX6ebqNp9s8tfWwF+yRTyejPRJ988L28YpIi4jLbH9FrAB8ISk7UsTcWlkZRQ3kOpCf+3Etjwi4k7SaP4g4PrsKp2ZWclJWhG4kpRHHtndxBZKMHL72Y6kc4HvkhZ52DIiJpVkx3VK0neBc7MvpwMrR8RHOYZkVUrSlsBjEdFcov0tTjrRbE8V1eFmSxTfRaoH/QdpZNn9WMtEUgPp+7wHcD+wU09uGWdm1Sf74PwQaZXEv0TEj0qy3xImt71IIyo+EXZT9sP+L6nmrTC6fmFEfCe/qKyetFGHezmpDjeX8phsosEY4CBSPei2ETE9j1jqSdZH+15gE+BqUg2uP1CYWbdJ6gPcRprQfCuwZ6kGabpdllCQzVQeSVoCcxvgoizhta47FViU+X8+h0raMKd4rM5ERHNEHA8cCMzI7h/KJhvl4Y+kxPYtYHcntpWRfZjZB3gHGAGckW9EZlYLsvzwMlJi+wwwolSJLZQwuQWIiCnA7qQT4TeBv2UjLtZJkjYAjmjjqQbgDxUOx+pcRFxBKgMYS+q1+4SkHSoZg6TfkPpqjydNIHN5TgVFxAfAbsAE4OhsqV4zs4WS5YUXAAeQ/rbsHhHTSnmMkia3ABHxHqlW70PgMOBPpT5Grcp+4H+i/Z/LdpL2qmBIZoVJoxsDdwKLAbdJOq7jV5VGdpxfAZOBnSPi5Uoc1+YXES8CuwJTgBMlHZNzSGbWc50FfAt4H9gh+wBdUiVPbgEi4nXgq8DHwFGSzs0mJ1jHRpJKOtrTApyZrcxkVjERMZ6U3JxOOm+cJumKrCazLLLE9jRSWcSeEfFUuY5lCxYRj5N+B6YBZ0g6MeeQzKwHUfIn4IfAJ6S5WW+W5VjlnBuQ9cC9A1gCuIg0IcWrCLVB0mDgNWApFvyh42cR8cfyR2X2eZK+QbqkNJBUY7/Pwi6R2M7+BfyONJltGimxvbdU+7fuydrD3Uj6+Z8aEb/KOSQzq3LZJOW/A6OAcaTE9rlyHa+so6nZ5cxtSUPPhwJXeNSxXb8GvsCCfyYBnJS1a+o0SUtImpDd2qrpNeuUiLgS2IK0isx6pDrcHUux72ySwf+REtuJpIVhnNhWkYi4G9gJmAT8UtJZvjJnZu2R1J+06NAo4D1gm3ImtlDm5BYgIl4hXWofSyoevlPSYuU+bk8iaRXgKFLiusDNgSFAVy8J9gYWyW59uvhas/lExPOkOtw7SHW4t0o6rjsTSCUNJPVV/S7pk/3wiHi0FPFaaUXEw6S5FZ+SFvG5tpwlKmbWM0laArgb2Bt4A9g6Il4r93Er8mk7q6nYAniCtKrSY5JWq8Sxe4i/AH1JiWtnfU/SGl3Yvvhn3dKF15m1KSImAF+jqA6XdHVmYFf3JWlp4D5St5XCCfDZ0kVrpZatIrQpqZxqH+A+SUvlG5WZVQtJKwEPApsDj5MW+HqrEseu2KWkrH3PV0m1WisBD0vapVLHr1aSNgK+RLrEW7iNBd4u2mwW6RJg4TYZmAr8sguHKv5Zu+7ZSiIi5mb9cPcmzaT/Oun/9oqd3Uf2f+BRYCPgEWDziPhPOeK10ioauLifNJL/pKTN8o3KzPIm6WukAc1VSQt8fTUiPq7U8StaJ5U1Xt8POJO0SME/JZ1Qz71wI+LJiFg7IlYquq1IWoqu4JSIWKToNiy7H9mFQxUvqOGRWyupiLiJNIr3KrAuqQ535wW9TtL3SUsvLgeMJp0APylnrFZa2Qj+zqSG7F8mjeC6rt+sDklqyHph30xaZfX3wP6VXt2y4pMAspGeo0mLPMwETgZulrRkpWOpcqVORl2WYGUVEa+SEtwbSR9eb5V0WlsfXiUNkXQpcE720A8i4hAv2d0zRcSs7MP2j0nnmr9JujjrAmNmdSArS/oXaU7QdNKqY8dFRMVzjtxmuGYzrjcD/kNa/eZ5SbvmFU8VKnUyWpwsuyzByiJbpXAf4HjSBMnjgH9IGlLYRtIWwLOk5XTfB7aLiP/LIVwrsYg4i7Sc5ofAIcAzLlMwq32SdgeeJ13FeRXYNCKuzSueXNu3ZKvebEjqfbYUqUzhbEmD8oyrSpS6RtYjt1YRkZxOqsOdDOwJPC5pHUknA/8GViDVYa0XEY/kF62VWkQ8SGoRdxNpfsUDkk6S1DffyMys1CQNlvR/pP/vSwLnAxtlnbJyk3tvwoiYFhGHkWpxJ5BWrnhN0t75Rpa7cpYleOTWyi4ibiaVKbwCrEYarT0BaAJ+EhH7ZiufWY2JiE8iYi/S6O1s0mXKpzyKa1Y7skljLwDfIw1kfDMijsjmV+Uq9+S2ICKuJ01EuR74InCDpEslfSHfyHJTzrIEj9xapYwjtYIJ5v1OjwHOzi0iq5iIGA1sQGrztjbwULbow7BcAzOzhSbpi5KuAP5Jmgx8LbBmVm5aFaomuQWIiA8iYj/SZcx3STV5/80uafXLN7qKc1mC9VjZjNmDSbVXh5M+1V9P+t07ArhR0tAcQ7QKiYj/kupwDyGtOvcj4A1JP86W5DSzHkBSX0k/Jp3Xv0Gqrd8/Ig6IiA/zjW5+VZXcFmSXM9cB/kha3OBE4GVJB9bRMo8uS7AeSdIepIkFlwCLAxcAqxV9cJ1EWqzh8S4uRGI9VFaHPZo0ensRqUXQn4CnJe2Wa3Bm1qFssGIkqQHAn4BG4Axg9Yi4Ltfg2lG1iWJETI6InwFrkdYkXoHUR/EFSQfXQZLrsgTrUSTtIOkx0sSCtYDHSCvSHB4R4wAi4p+kOtyXSc29H5O0T14xW2VFxEcR8W3Sgg8PkAYxbpH0aPahyMyqhJI9gKdJ5WTLAXcBG0TEz7PuOFWp6hPEiPhvRIwgrWP+MLAmaUToGUmjJPXJNcDycVmCVb3sE/2+kh4G7gQ2AZ4D9o6IzSLi0davyVYf24xUpjAYuC7rh1v15yMrjWzp3m2BfUkTUjYFbpL0oKS9/btglp+s/OBg0hW4m0jdTx4kLbKzY0S8nGuAndBjTiARcU9EbAnsSlqjeF3SikZjJf1c0iK5Blh6LkuwqiVpkKTvAa8B15HWDn8JGEH6VH9jR6+PiKnA/szfD/cmTzSqH1mpwg3A+qT6vVeALUkt4l6V9F1JA/OM0ayeSFpU0nHAm6RBxLVJS6PvHBFbR8R9ecbXFT0muS2IiNsiYlNga+AWUmeF04EPJV2dXRqtheV8XZZgVUfShpL+BnwA/B+wMmn53BGknrXXRER0Zl9F/XD3INXh7kaqw12rPNFbNYqIloi4ivSHdE/SZc9VgHNJ5/XRknbIM0azWlZ0Xn8XOI2UV90F7BkRm0fEHbkGuBDUyb9DVUvSmqQlH79JusQJ8DpwJXB1RLyQV2zdIWll4L/ZwAdQlQAAIABJREFUl9+KiEu6ub+tSDVuALtGxG3d2Z/Vj+x38euk0bW1s4dnkUZs/xwRT5TgGKuQRuzWAqYCh1brRAUrP0mbAEeR+p8XOuU8z7zz+ht5xWZWCyStSxqU+AZpsRWAKcAVpPN6roswdFePT24LslXNRgDfIV0iLXiFVNt3K/BoRPSIS/KSViO12wA4OCLGdHN/25BWhgLYKSLu7M7+rHZl9Y5fIS2juG/274LnSN0PLouIiSU+7iDgYlJCE8Dvgf/JY11yqw5Zudko0nl9naKnniKd128Hnu7s1QKzepW13dsM2IV0jl296OmHSef1q6thAYZSqJnktlg20jQiu61X9NRE0lD7PaRLqS9V6x/OrEVSoWh7ZERc1s39fZX0vgF2iIi7u7M/qy2SVid9KBwO7ERaRrHgP8BVpBPfi2WOQ8DPgd+SSnNuBQ4qdSJtPU/RSNMIUtlCwcfAHcC9wMMR8VoO4ZlVlWyQYm1SHftwYAdSC76CZ4GrqdErITWZ3BaTtCqppm9nUp1u8WIQk4FHgGdII1IvAq9FRHOl42xN0tqkWcSQlrTr1sofkrYnJfYAwyPi3u7sz3omSb1Il6DWJZ34NgC2IPWjLWgmfZK/DfhXRDyXQ5y7klr/LUIqM9qn3Im19RyS1ge+RhqF2hwoXgziE+ad118glTO82VOu2pl1VdY1ajXSOX1d5p3XhxRtNgu4n3S14+ZscZWaVfPJbTFJA4DtSEnulsBGQP9Wm80B3gLGZvdvAR8B44tuc0gTYABmR8SMMsS6LinhBvh6RFzdzf3tSBrdANg2Iu7vzv6sOkjqz7wPbENIi54slt0WB5YAlif1iV4eWJH5P+ABNJEu8z5Mqsu+NyImlzn0BcquwNxAOmFPI9XhXptvVFZtspXuhpPO61uQymhat4icRZoBXnxeH8fnz+uFvp0zI2JWmUM3a1OWqzRmXw7j8+f1pZj/vL58tk2xmcATpKvUDwD/LkeuUq3qKrltTVJfUhua9Uj1XOuQ/pAu3tHrzHqwiaRyl8KI1gvAUxExM9eo2pHV4f4dOIB5dbi/9CictSf7wLchaQSrcIViLea/JGtWSz4lnctfzO6fA56JiKZco8pRXSe37ZE0hPk/FS3OvE9Mi5BGyHqRRgcGlSmMRuBL2b8/Brpb5D0AWDr79wekkQyrDTOA2aTkbxKp3OZT0mjUp8DbZFcjemLtalEd7qmk/3e3AQf2xPdi+ckmp62Q3ZYlnc8LtyGk5Fekc++AnMI0K5hGuqo2l3RFYQLzrjJ8yryrEGOzvuFWxMltlZK0MWmxCkirPXXYFL8T+9sduDn7crOIeKw7+zOrNEk7A5cDiwJvkOpwe2SrPzMzK58et4hDHSn1imJexMF6tIi4nTRR4inSpLiHJR2Qb1RmZlZtnNxWr3Iuv+vk1nqkiHgH2Iq09PYg4CpJf856OJqZmTm5rWLlXH7Xk3Gsx4qIWRFxCHAk6Xf5KOBOSUt2/EozM6sHTm6rV6nLEjxyazUlIs4jNSYfR2rx96SkjXINyszMcufktnqVsyzBI7dWEyLi36R+1U8AywAPSDok36jMzCxPTm6rVznLEjxyazUjIt4FtgEuJi1QcbGkv2Wr9piZWZ1xclu9XJZg85G0jKQnJR2bdyzVJqvDPZRUh9sEHAHc5TpcM7P64+S2erkswVprJK28tEzegVSrojrcj0mjuU9mPaPNzKxOOLmtXi5LMFsIEXE/qQ73cdIHgfslfSvXoMzMrGKc3FYvlyVYl0lqkNQ/7zg6Q1JjqfdXqLONiPeAbYG/k+pwL3IdrplZfXByW71cllBnJG0s6QZJ4yXNkfSapPMlrd+J1+4l6VFSvekMSe9LOqn14gaSfiHpGUmfSgpJE7I63u9LUqtt/5g910vSlpIulfRvScdlz58j6UVJk7N9fSzpQUn7thHftZJulPQFSZdImg5Ml/SypP3aeU+7SLpL0hRJMyW9IOn/SVqhaJs+ko6X9AYwC5gj6TlJ+2d1uIcxfx3u3ZKWWtD308zMei6v6lO9XJZQRyTtCVxDStCuB94B1gQOBvoDIzt47VHAn4DHgOOAGcDOwInAcsChRZvvSKrdvQn4kLTK1x7AOcAQ4LSibVci1fieAxwOzMluH2TP7wl8BFwJfAosCuwLXCtpRERcW7SvtUglAq9k214FLAZ8Dbhc0uoRMbaN9/QRcEV2vxnwU2AqcJKkBuDaLP6rgP8HDMy+Z1dLGhkRl0fEeZJezr6/W5PqcPeLiMfb+56amVkPFhG+VeEN2B+I7LZ+Cfb3g6L9fSHv9+fbfD+bIcAEUtK3cqvnVgUOy/69cvbzO6vo+ZVIo5LXAg2tXjua9EFmtaLHFmvj+MNIE7DeavX4TdnxXiElyw3Z4/062NcKpCsDd7Z6/BVgZvZ72KuN38tft3rPTcBLwBKt9rMpsG/278Oy136/1Tb9gTeBtwAVPf4l4NHsNbOAb+f9s/fNN9988630N5clVK9Sj9y6LKF67QMsApwZEa8XPxER/4mICzt47SjSFZgTIqL178llgEi1p4X9jS/8OysRWBf4Cmlk9MvtHGPDiLi9sP+ImFW8LyXLSNqAlJiOb2dfH0TEORFR/Pt3S3a/YtFjB2fv6cSI+KR4BxHxWERcn335beC9iPi/VtvMJI1+LwcsX/T4+9n34kLS6PWFWR1u37betKS+kn7Y5nfEzMyqlssSqpfLEurHutn9wlwmL9TjXiopWj03ILtfovBAVq96AqmkYLFOHmNOWw9myewvSaO6g1o9PamT+57YKlaY9/14YgGvXR+YK+nJNp4r1NUuAXxW7hARs4HvSHocOJtUh7umpAMi4qNW+zgL+JakyyJiImZm1iM4ua1excmouyXUtkJitzAJ1MDs/hrS5fa2PAggaVlSAj0YuCB7/A1SScJ5pCS1UyRtCtxHurx/NvBUtq9Ps8c7q63f7QV+P7J62/7ZMa/pYP/vtfVgpDrcl7LXbkWqw90/Ih7N9l+YiNZCqnc+ewHvw8zMqoST2+rlsoT6USgV+DIpSeyKT7P7SyO1v+rI4cDiwMiIuKz4CUlNXTzuz0gttraNVhOzJM0llUMsrMJ7WoZUd/s5EdEiaTzQFBGnL8xBIuIhSRsB15Emq92XlSG8AJybbSbg+zi5NTPrMVxzW71KnYy6LKF6PZDdj2jryfZqQjP3Z/cHt7eBpMLP/gvZ/TNtbNbVc8HSpJHiZ0uwr9YezO4PaOvJou/H/cDqkjZpZ7tebT1eLCI+ALYDzifV4Z4P3Mu85FzZMbzKmZlZD+HktnqVs8+tk9vqcicpSfyGpGMLyZukRSQdA/y5g9eOBt4mtcY6TtKA7LUNkjaTdAvzyg1ezO5/JKlftt3ykv4O7NrFmF8kJX4/KSSRktbNjrdyF/fV2hhSqcQxWf/ewv6/JOl3wDHZdqcDzcD1rbbrL2l/4IXOLNoQEbMj4gjSCG2Qyh2Kr2o1Ad/p5nsyM7MKcXJbvco5ocxlCVUk60KwL/Aa8HtgmqT3gE+AM0jJVXuvnU5KTN8g9aidKukdYDLwCLATqS8spLra54HvZttNJk222oR2Lv934FRSn9zTSYtGTAOeI9Xztp6Y1SURMZk04W0K8I8s1vdJ9bPHA9Oy7R4HDsyO+Q/SohDvkGp1r2He6HJnrdvO9n2AUZIGL9QbMjOzinLNbfXy8rt1JCLGSloP2AvYnDR6+A5wd0QUugaMI01yeqnVa1+RtA5pQYStSH1rPyEly/8stOyKiBmSNiMltxuSEuD7SW2ztgeWbRXWOaRWXZ/7fYmID7Jj/gBYLYvt9uzWVnnFibT9YXp29p7ebLX/xyWtQur3vCFplHhs9n5eK9ruWkl3AfsB6wF9gfeBp4G7IqK5jWN+jqRRpO9LexpJZRJ/78z+zMwsP4roysCGVYqk7wGF/p1fznp0dmd/J5ESDIDerXqNmtWtrGb3AVJi3J4W4OmIcO2tmVmV88ht9SpntwSP3JoBkgYBlzMvsW0m/f9oneg2ABtJWisiOizhWHRRDW1u6bd/EBui+CikQQ0ten1un4Zbpn8y/YPW20sSsHwULT9sZmYLz8lt9SpXWUKEh+vNAIiIaZJWJa1mtiqpxGI1YI3sthTztzU7jNQG7XMk9Ro0rO8voPHnKLL6XI1TsEQo1NA8d/aQRfudPbX/7BPj/ZiRvaYfqdRhCLB7Wd6kmVmdcXJbvUrdLaGwP4/amhXJJvSNzW63Fz+XdZ9YtejW5qpu+pIGDBrWeDMwHGI80XCqGrh9QN9ZT09v6ru8gj0j9KMIjhk4o982gwcP3mPatGktpHrnD2mn7ZmZmXWdk9vqVa6yBNfamnVSRMwgtWlrq58vkMoKBg5rvAoYDtwTTX0OnDZt2sdFm7wEvLTkkjp7ZlPjxSL2m8vsO0gT/64EfuGrKWZmpeNWYNWrXGUJHrk1K6HBQ/t9R7A7xMPTBs3evVVi+5lx42LatEmzRzTPaXls1vTm9fo29n46Io53YmtmVlpObquXyxLMqpykxlCcAszoFTo43o2ZC3jJj2bNaFqm/6Dek/v277XzoCUHLV2JOM3M6omT2+rlsgSzKjdwkb77A0sSjJ40adYb7W0nqa+ki4BDgc179dbpwACamg+sVKxmZvXCyW31clmCWZVTpGWLG3o1XNLuNtJipIlqg4EtIuKdZnpdBoRgn8pEamZWP5zcVi+XJZhVPW0WMH3KhJlPtvlsajP2MGnZ4xHZBDVmTJjxjtIKdOtmfW7NzKxEnNxWL5clmFW/JQUftLXMr6SdSMsbnxoRP85ajn0m4L/AkCFDWKRCsZqZ1QUnt9XLZQlm1W8AMKP1g5KOAC4hjdaObuuFCpoAWloGuSWjmVkJ+aRavUq9opjLEsxKbzyweOELSb2BPwLbAptHxFvtvbBFWkxEDBw4bXrZozQzqyO9JXX2ktjUwqU3Sf2Bfp14zYyImJ2d8Ad3Yvs5ETE9O0aX42pLVvO2DCnet4C3I2Ja0fMD+fw68gsyMyJmdfE1XVXqZNRlCWalFvEm0iaDBw9eYtq0ac3ANUATsFVETGnvZZJ6DxrWuEbA2x99FE5uzcxKqDcwoZPbbgE8kv37eODXnXjNd4G/AVsC93Vi+6uBr2f//hjo04nXbAM8UPyApEHAT7Ljf6nV9i2SHgcuBkaTLh3u14njFPsf4HddfE1XlToZdVmCWYkFDfeK2Kwpmg4GvgPcAfwsIjr8fztwaL/tIAY3EP+oRJxmZvWkuCzhWTpOpKa18djHwHsdvOaTVl/PBF7uYPs323jsOaDdkdnWcUlaDvgnsFZ2vGuAF0jv7YvADsBm2W3J7JhPtdpnI7B2dtzn2jjmhx3EUyqlTkZdlmBWapp71dxmfjFnRvPvgB9HxLmdepnih+leV5U1PjOzOlSc3H41IiZ18fWXRcTRXdj+PxGxURePsWNEtE6S25SVS9xISmwfIU3m+FzyLWkX4ExAEfHzNp5fEXgDmLIQ8ZaKyxLMqtz0SU2bSMzuN7BPY+9evZo685pBi/XbRbAX8MyUibNvLXOIZmZ1p9a6JXwfWA8YC+zaVmILEBG3ARsBt1Qwtq4qdTLqkVuzEpHUS9JpwLF9+/bes6F3w/RQ/HnwsP7DO3rdoEUb11VLXAo0S/pcezAzM+u+Wktuf5jdnxwRkzvaMCJmRMTTFYhpYZW6LME1t2YlIGkwcAOwAbDJrFlNdyjiUKAvin8NGdZ4nJZR/1av6TV4WL8jFXoQtBhw9JQJMx9oY/dmZtZNNdMKTNJKwPKkkc7r842mJFyWYFZlspKlm4EHgR9GRBPA1EmzrxmySGNT0HBhiNMGTet33OBF+t0LfEhosUHDGocDSxLMkvTtKRNnXpTj2zAzq2nFye1YSR31U905Ip5o9dhhkvZuZ/vDI+KeVo+tIemNdrb/e0Sc2sbj/1lAXLtFxCPAqtnXb3bUgqcHcVmCWfXZGTg7Iv7a+okpE2f/Y+ASAx9raJ77c+AQYF8AFIAmBi0X9VHDyRMnznyrkgGbmdWb4uR2Eh0nPm11LBia3doyoI3H+gIrtrP9Yu08PpmOE7xCXIW+uBM72LYnKVdZgkduzRbSgrohTP9k+ofATyUdPXRo4wotvRqWCs2dOG387P921I/bzMxKpzi53WAhuiWc2cVuCc9FxPpdPMbGneyWMDO7byup7onKVZbgkVuzMssmir2R3czMrIJqaULZuOx+GUm9OtyyZ3BZgpmZmVkX1VJy+zQwm1QmsUnOsZSCyxLMzMzMuqhmktuImAncnn15fGdeU+UjvC5LMDMzM+uimkluM6eSkrc9JR3T3kaSGiT9FDi2YpF1ncsSzMzMzLqoeELZtyTN6GDbGyPi43IH1IaDJU3t4PmbIuIjgIh4XNL/AKcBZ0jaGjgXeJbUVeELwHDgSGAN4MSyRt497nNrZmZm1kXFye0fF7DtC0Aeye0fFvD8K8BHhS8i4nRJH2Wv2zO7teUR4I6SRFgeXqHMzMzMrIt608n6VODton/fCcwAWi/q0J43s+OMW9CGRX5J58omxrZ+ICIukXQtsDewJfBFUo/dcaRR3Nsj4pUO9jkhi3dWF+ItNZclmJmZmXWRIjpa/MvyIukGUnL+UkSsXYL9PQxsDtwdETt0d39mZmZm1ajWJpTVklKP3LoswczMzGqek9vqVepk1GUJZmZmVvOc3FYvd0swMzMz6yInt9XLE8rMzMzMusjJbfVyKzAzMzOzLuq94E1M0mBgMWAJYFh2A+gDDCrTYZfJ7peQdEQJ9rdYYb8l2p9VjxnA7Ozfk7PbeOCTiJicW1RmZmY5cCuwjKRlgXWAtYEVgeWz23JAY26BmXVPE/AO8FZ2exN4GXgeGBs+AZiZWY2py+RW0uKknq9bZPfrMW80trUJpJXZxme3T0mjZIUlgZuAaWUI80hgBdIiFX8rwf6OARYnJTWXl2B/Vh0GMO/D10CgH2mUvnBbAliynddOJa08+BjwEPBwRHxY1mjNzMzKrC6SW0n9gG2AXYCdgTUAFW0yC3iJ9If+ReA/pFGutyNiSkWDzUh6kLS62n0R8dUS7O+/wMrAlRHxze7uz3oOSQNIH5SWB1YiXZ1YD1iLlBAXe4O0LPVtwD0RUY4PbmZmZmVTszW3koYAewIHADuQRrgK3gAezm4PAa9ERHPFg+yYuyVYSUTEDNKHt5eKH5fUAKxKunqxJelKxurA97LbHEn/Bq4GboiI8ZWM28zMbGHUVHIrqQ+wBzCKNErbL3tqKvAP0mjUbRHxdj4Rdkm5uiW4z60BEBEtwKvZ7SIASUuT/u/sAuxYdDtX0t3ApcB1ETEzl6DNzMwWoCaSW0mrAIcB3wKWyh6eTBpxuhq4MyLm5BPdQivXIg4eubV2RcRHwMXAxZJ6AdsBI4B9SSU9OwNnSboMOD8ins8pVDMzszb16D63kr4q6WbSyNNxpAlT/wT2AZaKiEMi4p89MLEFlyVYziJibkTcHRFHAl8AdgWuIdXp/hB4TtK9knaXpI72ZWZmVik9buQ2qxPcn5TMfiV7+APgPODCiHgvr9hKzGUJVjWymvTbgNskLQkcDHyXNLK7HfCqpDOAMRHRlFecZmZmPWrkVtIOwBPAVaTE9nlSy6yVIuJ/ayixBZclWJWKiHER8QfSZLQ9gbtIE9EuBP4r6QhJPe6Ds5mZ1YYekdxm5QdPAXeSktpHgV0iYr2IOC8iZuUbYVm4LMGqWkS0RMTNEbEjsBUpyV2O1Jf5RUl75RqgmZnVpapObiUtK2k0cA8pqX2BNLlli4i4Pdfgyq9cI7cuS7CSi4iHsiR3S+BuYDXgH5LukbRevtGZmVk9qcrkVlKjpJNJiymMAt4FDgLWi4hr6mTJ0HLV3Hrk1somIh6OiB1ILfn+A3wVeErSWZIG5xudmZnVg6pLbiVtBTwLnEAaZTwRWD0iLq+TpLbAZQnWY0XELaSV0H5G6jP9I1Kpwm65BmZmZjWvapJbSf0lnQ38mzQ55U5gnYg4OVthqd64LMF6tIhoiog/AmsC1wHLArdIukzSsHyjMzOzWlUVya2k9YEnSb0zJ5EWY9g5It7MM66ceeTWakJEfBgR+wN7A+8DB5J65G6Tb2RmZlaLck1ulRwNPEYa3SmM1l5SZyUIbXHNrdWUiLgRWIe0EMSywD2STs1WQjMzMyuJ3JJbSYNI/Wr/AARwPKm91wd5xVRlXJZgNSciJkbECFLXk6nA/5CS3KU6fqWZmVnn5JLcSlodeBw4ABgLbB4Rp0eERxXnKXUy6pFbqxoRcQ2wCam93zbAE5I2zjcqMzOrBRVPbrNVxh4F1gBuBTaKiGcqHUcPULJkNFuyWNmXHrm1qhAR/yUluBcDywAPSDow16DMzKzHq2hyK+kw4F/AUOC3wO4RMaGSMfQgpSxLKP4513sts1WRiJgVEYeSWob1Bi6VdFzOYZmZWQ9WseRW0m+AC7IvD42IX7oMoUOlLEso/jl75NaqTtYybF9gBnCapL96opmZmS2Msie3WUeEs4Bfkdp87RoRF5f7uDWglDWyxUmCP1BYVYqIm4DtgI+AI0mjuH1yDcrMzHqcsia32cjL+aTViSYAO0XE3eU8Zg0pV1mCk1urWhHxJLA58AbwDeAGSf3zjcrMzHqSsiW32SSmi4HDgA+ArSLiiXIdrwa5LMHqUkS8RRrBfQ3YjZTgNuYZk5mZ9RxlSW4lCfgrMBJ4F9gmIl4px7FqmMsSrG5FxHvAtsCLwM7AVS5RMDOzzijXyO3pwOHAOFIpwhtlOk4tc1mC1bWI+BjYHngV2Au4QlLvfKMyM7NqV/LkVtIvgWOBT4HtI+LVUh+jTrgswepeRIwDdiQt9rIfcE6+EZmZWbUraXIr6ZvAb4DppK4IL5Zy/3XGZQlmfFaisDPpA/MRkn6ac0hmZlbFSpbcStoauIiUPH0zm/VsC6HVimIuS7C6l61mthcwC/iDpH1yDsnMzKpUSZJbScsA1wGNwE8j4uZS7LeOlToZdVmC9XgR8TAwKvvyMkkb5BmPmZlVp24nt1mLnuuAJYBzI+LsbkdlpU5GXZZgNSEirgVOAvqTOigMzTciMzOrNqUYuf0LsDHwKOBauNIodTLqsgSrJacA1wOrAGOyMh4zMzMAutVWR9L+wHeAj4EDImJ2SaKyhUpGJW0IbFj0usnZv5cq2uwrkg4ApgLNRY9P9iIb1hNEREj6FrAmsAfwE+DMXIMyM7OqoYhYuBdKywHPAkOAnSPirlIGVs8kDQamZF8eFxG/7+TrVgReJtU+d9X3I+LchXidWS6ymttHsi83jYjn8ozHzMyqw0JdzitaWncYcKYT25JbqLKEiHgT+PNCHO9Z4LyFeJ1ZbiLiGeAE0oe5yyX1zzkkMzOrAgtbq/Yz0trvzwK/Klk0VtCdGtlTSCvDdfZ1Afw4ItxFwXqi/wfcTSpROCXnWMzMrAp0uSxB0krA86R63Q29UEPpSRoA/Dr78paIeLCLrz8S+GsnN780IkYteDOz6iTpy8BLwEBgc9eOm5nVty4lt5IE3E5aDvN/I+KkMsVl3SCpF2lUfS3mLQbRWgAzgFUj4oNKxWZWDpK+T1qa93lgo4hoyjkkMzPLSVfLEg4mJbYvA78rfThWClmJwY9pP7Ele+4kJ7ZWI/4KPAisi1sSmpnVtU6P3GYz+F8Dlga26eqlcqs8SbcAu7XxVABvAGu7fZvVCklrkq5YzCJdkfgo55CsxL797W8v0dzcvJ2key655JLxecdjZtWpKyO3vwC+AFzpxLbHOIbUy7b1JxgBRzmxtVoSES+TShMGA7/NOZzcjRo16pZRo0ZdknccpdTU1LRWRFw9d+7cVfKOxcyqV6eSW0nLky71zQSOL2M8VkIR8Srpcm3r8oQbIuLWHEIyK7eTgU+BQ7JFTerZl0kDEmZmdaWzK5SdBPQDTomId8oXjpXBScBI0mIbAmYDR+cZkFm5RMRESSeSRnBPBXbJOaQeYcSIEUP79OmzZFNT03tXX331zHa26dXY2LiCpCmjR48e196+JOnAAw9ctqWlpeWKK654t6PjHnroocPmzJmz6AcffPDOvffe29zWNoXYBg0a9H7X3pWZ1asF1txKWoU0gWwasEJETKpEYFY6kn7KvOVJT46IE/OMx6ycJPUBXgVWBLaNiPtzDikXo0aNehYYN2bMmJ3a2+aggw5apFevXudGxH6kwY6WiLhH0sFjxoz5sLDdyJEjD5T0B+aNBD8fEUMkXTtmzJhji465H+lcs2z20HhJ/zN69Ojzirb5JCL+2tDQsFREfAvoQ1qR8dtjxoy5rrDdUUcd1Thx4sQ/A9/OtmmW9FxEbBgRm1966aWPdusbZGY1qzNlCSeRTnq/d2LbY50DvA68A5yWcyxmZZW1ASss6OAPcu0YMWJEr4aGhlsiYh1JO8ydO3cJYDtJy0u6rLDdyJEjd5V0KfAQsE1LS8tGwPmSFgcGFG8HXA1c0tLSsnxELCPprxHx11GjRm1XdOhFJP0qIhaNiFEtLS17A28BF4wcOXJIYaOJEyeeA3xb0skNDQ1bRMQuEfFSGb8lZlYjOixLkLQa8A3gE+DsikRkJRcRcyQdA/SKiDYvOZrVmDGkSbDDJW0dEQ/kHVC16dOnz+7A5sAao0ePfi17+IGRI0f+Arjm0EMPXfqiiy76qKGh4aSIeGHllVf++oknnlhY+fCpUaNGHVu8P0mnAFePGTPm10UP/2rUqFF7At8E7it6/A/FI74HH3xwS0Tc1KtXr7WARw4++OAVgEMlnTJ69OjPVp4bNWrUXFJLSjOzdi2o5vYnpNHdP0XEtArEY2USETfmHYNZpUREs6TfAX8ndQ1xcttKQ0PDtqSFXA4dNWreIoWSlgRoaWlZ+dBDD50UERsBpxUltp8zYsSIoY2NjRsAn44aNar11aFGYOXiB1pib4ZjAAAgAElEQVRfBZT0dkTQ0tKyRPbQtqS/Pdcs3Lszs3rWblmCpCWAQ0gnv79VLCIzs9K4DPgQ2EPSGnkHU4UWJbUJXKTVrQk4T9JE0kTihoiY0NGO+vTpM4w0YbVfG/u7LyLu7Oj1hRXlWlpaCp1dFgHo3bv3xwv1zsysrnU0cvs9oD/wl4hws2wz61GycpyzST1vfwIcmXNI1eYToHH27Nk/uvrqq+e0t9GoUaOmSlqmox3169dvwpw5c1oi4v5LL730hBLE9iHArFmzFsviNDPrtDZHbiX1Bo4AWoA/VzSiOiRpRUkHSzogu+0saQdJwyVtmN3WyrZbUdLikhaRNDTv2M2q3N9IV58OkjRkQRvXk4aGhtuBPv369ftB6+dGjRr1hREj/j979x3mVJk9cPx7kikwDEWxK8KAWEFFEdvaEFQUaS4qCPZVd+3KoGtZxE6xoe7P7ip2VIoNBbtiAxVUsMAAKioivU1Lzu+P94YJQ6YxSW4mOZ/nmSeZe2/uPTNAOHnvec97cmPv28+BUwYMGLBDZP+gQYOOxhtdBXj00UdXA9MCgcAZZ511Vovoc4mInHbaaW3rEpuIzAbIysrqVWnXjnU5jzEmM1U1cns87k3kLVWdm8R4MtUVwCb/wdSGyIb1GYpxi2yAa6sTwn04Weltu0FVX61HjMY0OKq6TEReAM7ETWrKtBKrPQcPHhzrZ35r7NixLw0ePPglVR09aNCgvUVkKq4V2KEicmZOTs7uwK8icrWqvpeVlTV78ODBM4GdRCSfSoMj4XD4ykAg8G55efmMwYMH3y8iC4CdBg0aNBD4Fji3tkE/8cQTswYPHvyOqt48ePDgbXGdXg4F+mzer8EYk0mqSm7/4T0+nKxAMpXXk/PkrCBc0L0Ja4uV8rASVli93vUgLi5Tikvd89XFSjgMYVVWeftLypTiUhoBjVYXhwmFK0ZUopwCWHJrMtEjuOT2XDIruZ3j9SnfZKU2b6liSkpKTsnJyblYRM4A+uM+IP8E3LTlllsuAXjyySenDxw4sHMwGDxbVbcTkaklJSX35+bmfqeqG2pin3766c/PPPPMLuFw+HpVHaKqWwC/Ap8FAoFHoy7/JV7ZQZRiEZkRDAY3TDQLBAInh8PhB4CLcB/WJ6hqP697w9o4/H6MMWlqk0UcRGQHYCGwDGilqlXWYpn6E5Hjgde6dczl6Uta1Hh8bYXCsLo4zNpipcs1f1EeYimwraqG4nYRYxoIEfkO2BPYV1Vn+h1PQzdo0KCdRGQhMGjs2LHP+h2PMcZEizVy+3dv+zOW2CbFQIB+BzaK60mDAWiRF6BFHhy8aw4fziltietp+VFcL2RMw/AEMALXt9uS2zoYPHjwLkChiHwSDod/CQQCO3h9sxfn5OTY3SBjTMqJNaHsFO/x+WQGkolEJA/o3ThHOG7f3IRdp3vHDec+IWEXMSa1PYdre3WKRBWqm5qFw+EwcLSqPi4iU1X1UeAPVe3mTSQzxpiUslFZgtfuZSGuTqq1Vq5ZMHElIgOBp/t2acQD/0hc44MFS0IceM1fAN+paoeEXciYFCYinwFdgANUdbrf8aQ6EWkKHALsBewSDAa3yc7OblFWVkYoFLL/G4wx1YlMaF8OzAVmA9NUdXkyLl65LKEvrhH3C5bYJsUAgJPiXJJQWZutg+yyXRZz/yjfS0Taqeq8hF7QmNT0Ai65PQmw5DYGEdkKV7oxANgV+AT4BvgsFAotCYVC6wAbrTXG1CQfyAO2wr2XnAM8JiI/4+6kPaOqlSeWxk3l5PZ473FSoi5oHBHZEjimRZMAR+6Zk/DrHbNPDnP/KAf3Z3xvwi9oTOp5BRgN9AD+7XMsKUVE2gBDgX7ABO/5pzYB1RgTLyISwHVvGQTMEJE3gdtU9cd4X2tDza2INAYOx/VI/STeFzKbOAXI6XNALtlZiS8BtLpbk+m8N9B5wN5eV5iMJyKNROQG4GNcL9ldVfUCVf3YEltjTDypalhVv1DVS4H2uMm9b4vISBFpEs9rRU8oOxK33O6UyDrfJqG8LgmNazouLrq0z6F5XgDgSK+WzphMNBlXenWs34H4TUR2x60+1gbXIu12VV3lb1TGmEygqmtV9W6gI9AE+FJEOsXr/NHJ7dHe45vxOrmJTUR2Bg7dccsgXdplJ+WaWQE4aq8cgFygW1Iuakzqmew9ZvS/Aa+/9tvAzap6pqou8TsmY0zmUdUVqnohcDnwioicGo/zRie3h3qPH8TjxKZaAwE56cBGJLMpUfe9rTTBZLyPcLN4D63pwHTldWn5L3Ccqr7gdzzGGKOqrwNHADeKyL/qe74AbKi33Q9YCsS9sNdsIiELN9SkW8ccgu7jzIleYbcxGUVVVwBzgNYispPf8SSbiJwI3Aocparf+B2PMcZEeJ2cDgMuEZFB9TlXJMHpDOTgepBZC7AEEpE9gY677pDFHjvGWiAucVo0CdC5bTbANrg/c2My0cfeY0aN3opIR+AB4ARVne93PMYYU5mqLsZ1tLlVRA7Z3PNEJ7cAn9U3MFOjwQD9D0ruqG1E932sNMFkvEg3mIz5gOfNRH4OuFBVv/M7HmOMqYr34ft04CmvbWqdRZLbvb3Hr+MRmInNW/bzVBHo28Wf5PaYirrbnr4EYIz/ZnqPe1d7VHr5D/CBqk7wOxBjjKmJqr4HPAuM2JzXV05uZ8UhJlO1Q4E2Xdpl06pl0JcAdtshizZbBwE6ZWLNoTG4ZSDLcS1o0p7X8msgtnCFSSOCyIXjOuT7HYdJqJuBo0SkS11fGBCRILAHsAL4Nd6RmY0ktbdtVbq5BR2EihXpjMkYqlqCW+t8exHZ2u94kuBaYIQ3mc6YzXL1uHbN/Y4hYvirO+YNmVjwfF7OuteGj+uQ+CU+jS9UdT3urtOwur42ALTGLd4w2yaTJY6IZAEnBQPQc//cGo9PpG5WmmBMpO50V1+jSDARaQUcBTzqdyym4brkjfa5oWzeKZxQ8NLlEwpa+BnLVZN23mFNee57QH/g8NU56x/0Mx6TcM8D7b0JsbUWAAq850VxD8lEOxbYpmuHXLZq6m8XrkN3yya/kQB0E5E8X4Mxxh+RbgFt/AwiCU4HnvJGQIzZLLklodGI7odIvyyRr698peAgP+K4clKbTmHN+hThgMg2Qc8snFBwmR/xmMTzlgF/BDizLq/LouLNfUFcIzKVuZIEnyaSRcvJEo7YM4fXvixpjBvVec3vmIxJsgXeY0F1B6WBAUBcVvzZXCJyBHCd920JsM57vgYoAxRXFlef/T+p6uoE/QgZrXBi2xMRLoza1DoQlg8KJxZcP7r3gpFKcu74Dp1YcEqAwOO4O80bE7lj6Ph2c0f2nfdqMmIxSfc08JmIDKlthUF0crswUVFlOq8NT++8HNHj9s1N4ppkVevWMZfXviwB1xLMkluTaSIjt2mb3IrI9kBTVf3W51DOJvHLHY8Chib4Ghnn6lfb7Qz8DzdHI1o2yO2FEwsOuaK01Vl39v9lWaJiEESGTGg7DJH/xIgjYhmE7cNNmlLVRSKyBOgA1GrxmSxgR+/5L4kKzHAU0KQ8jE74opiBf/N3Qhm45FYEVOkpIhdavbXJMJH3u3TuGHIk8J6fAXirX/ZtlC289u8tCYXd28zaEqU8BKqwcl0YgNJyWF/q9q8pVsrDSjgMq9e7bSXlutH+UBjKQ8rrX5WAmz9gyW2clZexswQor2q/Qq9gTvaXhePbDBjVd8EnVR23uS4c1yG/MKftWBXtU+VBwkwtp/eofvNtgC69vYNbnrfWye1W3vMliYrI8BpQWFqut13+xKqsT38qY8RpTWmc488g7vI1Ya57bnXkZtJOuNF7W7HIZJLI+11LX6NIrL2o6Onrl15A02P3zaVDq8SsyHjYsKX8+Fv5HiKyi6rOTchFMtTovvM+Khy/S0cC4bHAMVUc1ppA4IPCCe1uyZ9ZdOOwYRqOx7WveLXVjnk52RMV9q/6KH29JDtrwJheP62KxzVNSpsF1LrWO0BFcrs0IeEY1BmNG8H97flp6+l+8zJ+/K3KD8QJ8953pRw5fCkTpxcjbvSqmy3FaTLQUlyt5lY1HdiA7Qr86HMMAwFOOjBxcw2iFqaxVRcTYFTfuX+O7j3/ONCrgVAVh2UhOmztvgVvDX29YLv6XrNwfJuDg6Hs6VSb2DIm/+sFJ47pYYlthvgB2K22BweoGLmw5DbBVPUjYF/grZ9+L+e4W5fpxC+Kk3Lt4jLluudWc+o9y/ljRRhgnMK+qvpOUgIwJoWoahmwmvQeud0K+NOvi4vIFsCxzfOEo/ZKXCvS7ntvOLe1NkwQRXVU7/kjJKxHA79VfRxHUyZfD5nUtvvmXmvIhHYDCATeBqpKkksEzhjVu+jSeI0SmwbhT+owGBEAmgHlqromYSGZDVR1CW7xhOFrS1TPe2glQ8auoqw8cSWvM4rK6Dp8KQ+/vQ6Uv4CTVPVkVU3YJABjGoAVQL7XgzodNcV1FPBLfyC3V+dG5GQlrgTrgHY5bNEkAHCEiKTMQgPpaGTf+e9rMHsf0NerOkZhW1HeKJzQ7oaTx0mtl+IURAontLtBRJ8hVkcE53fQI0b2LnqyrrGbBm817j2tVgJALq69ikkSVQ2p6g3AMQJLxn6wnp4jlvPL0qru+GyeshCMmrSGniOWMW9xCGCywj6q+nJcL2RMwxR530vXFY6yca2y/OKtyJjY9ofBAHR1i1RlA5s9YmhqZ3TPH/4a3XtBTxW9jKr/fgURHdY6p2DqVZN23qGmc144rkP+kAkF4xGteiUqYaaGOHhU7/mfbWbopmErxeWrtRLAvbGXJiwcUyVVfdsrlv/k6wVldL9pmb7zbXz+KH74rZwety5l9CtrUWU1cL6q9lDVKm8pGZNh0j259Y2I7AActl2LAAe1T/yvt7vV3SaVojq61/x7NCCHUv1k5CPDZH09ZEKbHlUdcOXEXVrl5az7AKF3Ned5MT9QcsjofkXWEcHUiiW3PlPVX4DDgRHL14Zl4Jjl3PzSGkKbWUkUVnj47XV0u2mZfvNzOcA0VfZT1YfiF7UxaSHyvmfJbfydBgROOrAxgSQ0hTm6Yy5Z7gb4CSK1vxVu6mf0ifO+CJZKJ2BclQcpW4sEXiuc2Pae8x/qnB29a+ikXQ4NEJ4OdKry1ciI/K/nnzKs56J1VRxjzCYCuFs5yZ+2bzZQ1XJVvRroB6y6d/Ja+t+1nD9X1i3D/WVpiJNGL+e651ZTVq6lwNXA4dYex5iYLLlNnKSUJEQ0ayx0aZcDsDXQJSkXNQDc3n/eylG9i05W5XyqLnEU4JKm2y77qPCVNgUAhRPanqMafgfYporXFKOcPqr3vKtt4pipq4D3aA38U4CqjlflAOCbj78vpfvNS/XzubUrmXvhk2KOGLZUp/1YCvCNwkGqOsJbl9kYs6nI+15KrBqYLkRkD2Df9ttnJay3bSyJKk0Qkf1EZP+or31EZHsRCdT86swxuk/RQwGRv4HOq+oYgS6EA18UTix4GuERqvxgKYsCIoeN6lP0VILCRUSaVPpz3d/7s27rrSpqGjD7x5liVPVH4EDg0T9WhKXPqGXcO3ltlat3L1kV5vT7VnDxYytZW6JhYATQWVW/Tl7UxhizwWkAf0/SqG1E930S1hJsGjA96utrXDusYhF5U0T+FufrNVgjes2bXpKTtR/CC9Uc1hJkYJV7lS8CUtZlRK950+Mf4Ub2ZOM/1+nADGAesFJE3hKRqsolUpqIPCsi00Xkc79j8YsltylIVder6rnAGeEwxTe/tIYz7l/BynUbZ7ivzCjm8GFL9c2ZJQBFwFGqerWqWg21MSbpRESAAQC9D0huctt+uyzabhME2EdEWifoMsujnmfjVu16T0TOS9D1GpwxPX5aNapX0SkCZwB1q5MVXsjPKjlyRK+fkz3xuRzXGjAiiOu8MVVEGuJCL3viJqtXtwhGWkvX/o5pQVWfFJFvgHFvzixpd+wtS3n0gha02irIjS+uZuwH6yOHPgRcab2KjTE+Oxho27ldNgXbJH9eV7e9c3lo6jpwvcT/LwGX2F5VS0SkLXA5cBEuEbpPRGao6gwAETkO15MzpKovi8g2wKHAz6o6Q0T6ea9bq1rRMzZq+xpVfSNqexZwEnAIrt/nh0AxFfWq41U1pebOjOxd9OSQia2nC8HngQ41HK4gI0f3Kvq3VnmfMqG+UNVDAESkC/A6boGXLYFjgacjB3rlKEcDf/OO+Qt4V1Xfr3xSEcnDJcntgRa4Ef93VPX7qGMEt3rp4bhFCpYCH3jHqXdMcyqWP14IfI+ra2/jfT828v+/iJwENI86fX/v+QJV/SLqmt28n2FL75rvq+q7leL/G7C99+2ruBKuzkCJqqZ0SzbB1Z39qqqt/A7GxOat9PMEcGJutmiLJiKLV4QRWKRwlqpO8TtGYxoaEZmGS8Z29rqWpBUR+Rror6o/JfGa9wIX3TqgKed0zUvWZTf4cE4pf79zOcDrqhqX2lsRKaaiv2YjVS2J2vc4cKb37dOqOsjbPgfYHTfBajjwH6ARcLOqXi8ia4E8oEhV20WdL7L9J1Xd1dvWDJhC9RPl8lV1bX1/1kS4cFyH/LycdfcDp8c+QtarMGh0r3lJ7b8uIgcAkdv2n0SSW2/fFFzyBzBYVZ/ytu8AjCf2n8VzwGmqbvKbiPQEHsNNcqysj6pOFJGtgZdxSWZlE4G/q2q5iHQEZnnbvwW2AHaMOvZ74BBVXS4iJcSuZf6fqp4lIi29cx8a45ipuEWeVnk/w6tU1LBfBlzr/TzPqmrVpSUJ4CX4c1S1xr7JYGUJDYKqLgd6A1eXlGlosVs+9xmFjpbYGmNSgTe62D8YgF6dk1uSEHHQrjk0aywAXZM0KSi6xWLXGPtzgVtxie3mGkFFMvW79/3NwJJ6nDNp7u//7ZpRvYvOECFmO8pgIHBmshPb6ojIYbh5L+DKFT72tgsuEe0CLAZOxn04jkx6OxUvgfeS0ZdwiaACz+A+4LzgnTPy9+F5XGK7DDcSexDwiLevN3B+jBB3B2YC/8ONGke2XeU9f8Q7H961H/K+IiPLj1GR2I4HLgQme993A+6t4ldzN7ET9ZRkZQkNhHd7YoSIfApso6pV9xU0xpjk6w5se+SeuWzdzJ9xk+wgHLlXLpOmFzfC3TqelOBL/hz1fBsRkcitZE858C9gjvd8ZV1O7vXsjYyQlRHV2lFEjqIBJRsoHwOb1CaHynW2D9FUdoCILMOVhDTztikwVFUji1T8jYqk97+4UU5wI/ODvOe9cEnnZVSMnl6vqrdELiQiBwLrRWR/XDkCuIQ0kmAOB87B3VnvBdxfKdbnVHWwd67o0edjgKtV9UKvnGBLXOqwIUEWkZ29cwLMxd3ZCYnII7jFOHYAThORy7xBtWi34BL9MlxpTEqz5LaBiVXXY4wxKWAgQN8u/ozaRnTrmMOk6cXgbqcmOrltGfV8aaXEFqBcVR+u5/kjydZPDblneVhRSd2me1m4W/3R/qmqD0Z9v1/U8+HeV2WRW+bRXRaeiT4gUqsqIudGbR7qfVV1vphU9QsRWQ80BmozibJj1PPPI61CVbVURL70rhfETUj7uNJr/09VF9XiGinBkltjjDH14k2c6dM4R+jRqdbLvydEt465BAMQCnOiiFwQI+GMp75Rzz/ZjNdn17B/FW4EUWpxbIMUCmgqpLzfAGcBF+O6PAAMEZHnVTXSRSE6X/oIiDXivDDGsVUtbBF9zKdU1NRG+726oL1Sicjvrza3S6JneVZuol9WxXENkiW3xhhj6qsXkH/sPrnkN/I3V2nZNECngmymzyvbHjeC9mW8r+GVCwwG/u1tUuCeOpyiBDdxbFsRaaaqq7ya5Y1+eapaLCK/4SYP7SIi3VR1qoi0wN12NvGxxuti8U9c+6wOwC7AEyLSx/uA9H3U8Yuib/fDhprztt6331MxSnoMrlQhctxOuFrs6PP9FeN8QVyXheocQkX9bnRyHFnRLSAiOVHtQX+IOmafqGsFqOhoocCPNVw35dmEMmOMMfU1EOCkJC/cUJVjKlYrOzHOp57m3b5dDDxORReF2yq3UapBZBWvHOAzEXnB29Y4xrGR29oCTBGRxbjJZHvUNXg/SQNYCVVV1+MmikU6T/Si4gPMFCDSeeQUEXlJRM4Qkb4icjVuJPdab/8DUae9T0RuEpHTROQG3Ietzrh2bt94x/QUkVdE5CzvfIW4ZPXmGGHuIyL/FJH/4Ca4RTwS9fzXqOejReRkL0n/AbcoCcC+InKn17bufioS6ddV9Y8qf0kNhCW3xhhjNpvXWujY7Czh4F2rWE01yRK1FC+u7rITFbW2i4BzVPXaql8S0x1UJHu7A/29c8Vab30YblZ9xDa4xCe6fV1K9biti6CkRFnCBqo6B9dBIOJGb8S8FJfsRkY/++FGZF8GbiNqlFVV3wEuBUqBJsB1uK4Kw/AmAXr1rn1wrb3Araz3mHe+kbi611g64ia0Daeiz/HjVHRtgKiRYlypxfO47gvgOjoUec8vB94ALvC+n02MSX8NkZUlGGOMqY+WAivKynWbvqOX8cgFLWiztb8le9u1CNA4R1hfqp1FZHtVrbZ2sQYXsnENYilu5PRX4JtIX9NKhuGa9odinVBVn/NGYHvhFnt4DzdCeybu/+WVUceuB071RvN2xSW1P1NR37k8uveuqbVfgau95xutiKaqT3hlAZFuFK297d+LyN64RPRQXLlIKW4k/yPc6G7kHGNEZCIugd0Ft0DD77g/68neMUXeEr/H4xZx2An3AWcxroY70kEh2ovABOAA7/vJqrrRcar6kogc5MW5DW6luNe9ffNEZB9ch4dDcR/UluBahT2jqsVRp/ofboQZXP13g2GLOBhjMpIt4hDXa22Pa2J/eLPGovee3VyO29efiWVTZpVw+ROrWLIqDC4B7J7MhSziTUR2w/UpfRtXupCPG+k92jvkGVU9zafwam3IpHanibcYwkaEfUb1Koo1mcp4Ki3i8FSkFVgmqesiDjZya4wxpl5U9XcR6Qpcv2q9Xn/m/Svk3KPzGNa/KdlJGsRdX6rc8vIaHnlnXWQB13HA+TH6dTY0ObhRvcNj7JtHxehjgxQOkVJlCSY9WHJrjDHpqZj6rYxVJ14N4Q0iMh0Y+/Db61p883MZD57Xgu1aJHZ6x/R5ZVz82EqK/gwh7hbreao6IaEXTZ6fgULcre0tcXNlfsWtUvW8qq7zMbZaE039CWUpbCXuwxpULNqQaRrjyitqxZJbY4xJT6tx9ZxJpaqvejV9L3z6U9mBXYcv1f+e21yO3Cv+k83KQnD3a2u487W1hF3l6xvqJnjVp8Y2pajqSmC033EkSqpNKEtFqvozrotDJmtKHVZGs24JxhiTnv6ghhWOEsX7z/gIYMzSNWEZMGY5oyatIRzHsbvvF5Vz3C1LGf3KWjTMalwJwvHplNgaYzbYiRoWtYhmya0xxqSnH4Dd/Lq4qpao6qXAYA2zbvQrazn5ruX8tTpWc4HaCys8/PY6ut+8TL/9pRzgY4VOqvpQPOI2iaFWlmDqZzc2XoSiWpbcGmNMevoa1yzeV6r6lLpVn777cE4p3W9aptPnxWrnWrOf/wrRb/RyrntuNWXlWoqbTHW4qs6r6bUmNaXI8rsm9e2PqzOvFUtujTEmPX0IHOb16/SVqn4PHAQ899vykPQauYx7J6+t6WVRr4exH6zniBuW6ic/lgLMUuiiqiOq6DNrUowE4lmUYjJQV6DWqwBacmuMMWnIm4g0m9gtpJJOVdeo6gDg/FCY0ptfWsNZ/13BqvXV5zxLVoU5/f4VDBm7inUlGgJGAAeoqvVGTQPBgLUCM9Xz+vwWq+rCGg/2WHJrjDHp6ykgpRq+e7WxhwDzX/+qhGNvWcqcRbFXj500vZjD/rNU35pZAm7J0CNV9WpvKVRjTGYYzMbLC9fIkltjjElfzwPHi8i2fgcSTVVn4JYPfaNocYjjblmmz3y0fsP+leuUix5byT8eXMnytWFwK3Ttraof+xOxqS/rc2s2h4g0xS0V/GRdXmd9bo0xJk2p6koReRy4ArjK73iiqepSEekJXFtcpsMuf2JV8KsFZXTrmEvhU6tYvCKMwK8KZ6rq237HaxIjXJ5lZQmmOhcCr6jqorq8yJJbY4xJb3cAM0XkEVX9ye9gonmTwW4SkWkCzz75/vqtn3x/wwjuWIWLvdph08Cpilp1rakLEdkeuAQ4sK6vtbIEY4xJY6r6FzAc+D8RScn3fFV9W6ET8BFu+dyTVPV0S2zTX9BagZmqjQHuVdVf6vrClHyjM8YYE1cPA2txfWFTknfb8ShgT1V92e94jDH+EZELgFa4O091ZmUJxhiT5lRVReQc4DMRmaOq4/2OKRZVLQf+8jsOE38SQNWmlJlaEJGjgGuAQze3M4qN3BrjKXxruybD3zvKPvBtBhFpKSJPi8hZfsdiYvPKE3oC94pId7/jMQYgJFaJayqIyIHAWKDf5pQjRFhyawxw/kOds1mf99LaFQtfv+SN9s38jqchEZHjgW+AgcBjIvKYiDT2OSwTg6rOAXoBj4rIqX7HYzKI8gcwtfJXUHWVr3GZlOH9X/ISMFBVp9frXIACv6pqq3gEZ0xDVDip4L+o/NP7dlYgFDxhRL+ffvU1qBQnIvnAaOA8QHp1bsSnP5Xy58owwCygv6r+6GeM1RGRacDBwM71GSFoiERkF+AVYDJwlS2KYIzxi7dE+PW4xRr6qOo39T2njdyajDdkYsF/ohJbgL3DwfCnQycU7OtbUClORA4CZgDnb5kf4PF/teDh85vz3rCWHLFnDsDeIswQkVP8jdTEoqpzcYsotARmiMhhPodkjMlAInIA8AmwN9A5HoktWHJrMtyQCW0HC3LDpnt0R0SeHD48NVsn+UVEskXkBlzLpl27dsjh3WEt5fhOuQC0bBrg2ZMNPhcAACAASURBVEu3YMiJTRDIB54TkQdFJMfHsE0MqrpGVU8HhgAPi8gk70OLMcYklIjsIyLP41ZRvE1V+6nq8ridHytLMBlq6PiCIzQgbwK5MXavCoc5/I6+RTOTHVeqEpG9cEsg7tc4R/Tafvlybtc8pIrpIB/OKeX8h1fq0tVhAaYDJ6vq/ORFXL1MLkuoTESygAHAUCCEW8f9DWC22hx3Y0wciMhuwLG4+Rlb4sranlDVkrhfC0tuTQYaMrH1nkLwI2CLGLvLVDhhdK+iKcmOKxWJiACXCIxUyOncLpv7zm5OwTbBGl+7aFmI8x5ayfR5ZQgsUxikqm8kPuqaWXIbm4h0Bk4FugHbAd8BPwBLgTU+hmaMaVjycKVPuwJ7AStwEwlfAKYl8oOzJbfGN5e80T63UZl2Htlr7sfJvO5Vk3beIaxZnwA7x9itKnrW6F7zn0hmTKlKRFoD/wOOzArCZcc34Yqe+QTrUKxRHobbx6/h3slrwb3fjASuVdVQAkKuNUtuayYiWwC74/5z2hpXatLI16CMMQ1BCe7D8BJgHu4u0NJkXdySW+ObwokFl4DcA0zVgFwz+sR5XyT6mldN2r1pWEvfxy31uQlFh43uPf/G2p5PRC4FhgErgTJgFVAM3K2qL8YhZN+ISH8RHlKlxe47ZnHf2c3puPPmtwF+46sSLnl8pa5arwK8DwxQ1d/jFnAdWXJrjDHpyZJb44vCt7Zrwvq8ubjbnhFTRbVwZJ/5XyfimiePk2CbnIKX1fX5jEGfGd17wSCldrdKROQq4PYYu0aoalyXOfV6kt4FrMMto1oKLAeuV9VP43ytbYAHgT4BgXO65vGfv+eTk1X/XuvzFoc494EVzP61HNwn+gGq+na9T7wZLLk1xpj0ZDPBjS9kfZOL2TixBeimIjMKJ7Z94crx7XaN9zVb5xSMqSqxVeTd/NImZ9UmsRXnLjZNbBUYEu/EFkBVnwPGAG2BjsD+uJrIySISt5ZlItJDYCbQp1XLIC8P2YKbT20al8QWoN22QSZfsyWDDmsM7jb3myJyg4h1pTDGGBMfNnJrku7qce2ah3K0CDdbsirlwLOhUOiGO/stLKrvNQsntr0WuDnWPkW/Cyl/u6vP/BU1ncdrafUEbsJNtBBwnqo+Vt9Ya7j+SKCw0ubfgL/VpxOBiDQDRuEWZKD/wY0YcVozmuQmbmXMFz4ppvCpVVpcqgK8CpyhqssSdsFKbOTWGGPSk42WmKQry5G9EGqaTJQFDA4Gg7MLJ7a9Z+jrBZVHeWttyKR2pwE3xd4ri4KhrONqmdjmARPYNLEtwbW5Smhi67kKeKTSth2AKSKyWb8jETkE+BI4b6tmAX3yohbcd3bzhCa2ACcf3Igp124p7bfPAugJfOWtK26MMcZsNhu5Nb5wNbeNLwK5itjtuCpbBzxCOHDLqL5z/6ztdYZManu4KG8Ru5ftalE9vDY1viLSAje6eGilXSuBE1X1w9rGVF/eUoXPAv0r7foGOKK2jbBFpBFwA24kONBzv1xGDW7GlvnJ/cy7pli54olVTJxejECpwlBVvSfR17WRW2OMSU+W3Bpfue4FJf8CuQZoVouXrAG5P1jKbbf3n7ey2nOPb7NHOBD4mKp62aInju49/82aLuiNiE4G9qm0azHQQ1W/qkXcceWVR0zCNcSO9inQTVXX1uIchwAf52YLd57ejL8f5F+HJ1V4+O11DH9xtZaHEOAZ4HxVTVhfVUtujTEmPVlya1LCkFd320pC5UNALwEa1+IlS0FH5QdL7x3Wc9G6yjuHvl6wnZbJp0DrWC9W0X+O7jX/gZouIiIFwFvALpV2lQKzgb9wo8olbNoObD2w2tu2wjtmHa73Xxmu20GZ9/26uq7SIiJNgXeAzpV2TQF6qmppda8//pL2ubOm/Pr72qVlW3x+XUua5yW2DKE2ps8ro/fIZZSHAdhdVX9I1LUsuTXGmPRkya1JKVe93H6ncDBUCJxP7FKCjQlLUL0jvzn3DDtyfjHA8Fd3zFsTyn0HiFm/KciNI3vPG1abeETkVeCEWv8A9RcrQV7lbVvJpglyKW4S2LaVzvMMMFhVw5EN5z/UObvZ9isOQ0OHicphCgcBTd57fBn/2Bb6HOB/b/6ZC8s45uZlADNUtXLSHleW3BpjTHqy5NakpCEvt20dyOIaVc7GTS6ryS+q3FyaG3wityT0PELvWAeJ6LOjei04rQ69bLcCPgD2qH30KeO/qnph5JsrxrVqHMzJXk6lDw1zP1tH8J2V/Pfc5kkPsLJhL6zmgSnrAK5U1TsTeS1Lbo0xJj1ZcmtS2pCJrfcUgsOBk3B/X2uynKomqKm+k1/WpMew/t9We7u+MhHZEfgIaFNp1xPAjbgyikbe4xZRzys/xtpX3bb6+gXYX1WXRDYUTiz4GOSQ6IPWrw7p0//8Vb67Y2uyfOyfElboNHQJf6wIh3EJ56JEXs+SW2OMSU+bv5amMUkwuvfC2UD/Kye16RTQwE3UXCJQVeeFb4NlgX51TWwBVHWRiHTHJbjRt//PAIpUtdbL9daWiGQBTalIepsB2UBz3Mhrnre/FXC5tz3a98Cx0YktgErgI1HdKLlt3DQogRZBps8r5aD2OfH+UWpt2g+l/LEiDPBeohNbY4wx6cv63JoG4Y5eC74a1buoZzigBwtUvVxr7GKD3zVEz5q6K1RHVefiOhNU7oc7XEQu39zzVnO9clVdrqq/qWqRqn6tql+o6lRVfU1Vx+Faf13EpontDOBwVf258nkDIWK2LNtpz0a8NbPOeX9cvfx5ceTps37GYYwxpmGz5NY0KHecOP/Tkb2LuoVVuolre7WxyoULypqwhE8Y3a9oYX2vraozgb64iV4bhSUiZ9b3/HUhIl1xSf5WlXa9D3StPGIbEcwp/xgIV96+056NeGtWnZo1xFVZufLalyXgJsi97FsgxhhjGjxLbk2DdEefeW+P7F10MEh3VL6s6rhQgBvv6LUgbn1oVfU94BTc8sARAjwkIknpqiAifYDXcGUJ0V7B9d1dVdVrbzth4XKB7ypvb9WxcdlPv5dT9GdNC8clxtRvSlmxNgzwejKX4DXGGJN+LLk1Ddqo3vOmju5T1Bnk6lj7gyp/xfuaqjoJOIuNR0CzgXEicli8rxfNGyEex6YTzsYC/VR1fU3nUDYtTWjaMpjddKsspvo0ejveShKMMcbEiSW3psFTVLOyyh+qYm9CWnip6lPApZU2NwZeEZFOibimiFwFPMamE0HHAGeoavmmr9qUqnwUa/uOe+T6Upqwplh5a1aJ4nr3vpr0AIwxxqQV65Zg0sJtJyxcXjix7R/AdpV27Zmoa6rqfSLyG7AD0MT7ygF6i8gsVY3LPX4REWAEUFg5BOBGVb2hLucLZ5V+EAxlb7J9546Ni995cG2jles0qauVvf5VCetLVYCXVXWT1eaMMcaYurDk1qQNReYImrTkFkBVkzH5qTUwF7gKV/4QaRH2hTeCXCd39vxl0ZCJbRdIpb69bTo1Li4P0ej92SX06py81crGf76hksJKEowxxtSbJbcmjehs4KhKG1sXvrVdk1HH/LHWj4jiQVUXAFWUXWwecXW3baK3Nds6q3mj/ABTZiUvuV26Osz7s0sBlgBTk3JRY4wxac1qbk3aCMCcWJultNFuSQ8mxakSq+5WdtyjUfmUWaWENmkWlhgTviiOXOv52tYMG2OMMdWx5NakDZHw7FjbtTyQ0NKEhiio4ZiLObTrkvfb8rVhZhSVJSUO65JgjDEm3qwswaSNEgKzN50mBSrUq2OCiDQC2npf+bilcJvg2nE1BtYCq3CLO6wBfscty/tbfa6bSCP7Lvx+yMSCP4FtorcXdGocBpgyq4Quu8T6bcbPr0tDTHdJ9ELgk4RezBhjTMaw5Nakjbt7FS0unNh2KdAyersgtU5uRaQdcJD3tS/QDth+c+IRkWJgPvAD8DkugftCVX2v/1VUh9JumqJ9orfnt8zaMTtXeHNmCdf2y09oDC99Voy65ZKfVtXYCycbY4wxdWTJrUkvwhyUv228UassSxCRZkAPoB9wJJVGMnErkc33voqApbiR2hJghXdMDm4ktxluNHdnoAA30ruH9xVJIstFZBZuhbHxqhq31dPqKqz6kQgbJbciZO+0Z6NffvhqfasFS0K02TqYsOu/bCUJxhhjEsCSW5NelDlQObml3SVvtM8d0+OnEthQZnAybhndo4Fc77hyYAZuhPVT3GjrAlXd7AJUEWkBdMSNBB/sPe7nfV0vIguA8cDjqvrN5l5ncwThw1jzxnY/PH/h/K/Wt5r6TQnnds1LyLVn/1rO94vKAWap6rcJuYgxxpiMZMmtSSter9vKm7Nyi7W9iKwHzgfOpqJ0YTluOdvxwJvxLhlQ1RW4tlsbJnCJyG64kdy+QBfgcuByEfkQ+C9uMYPSeMYRS16L1l+uWblwDa6OeIOCTo1zwdXdJiq5tYlkxhhjEsWSW5NmwrNh09W13n50yaNAZ1yHkDLgReAR4J36jMxuDlX9Abfi2AgR2RE4FbgAOMz7+kNEbgceUNWErYc77Mh3y4dObPuZutHrDfJaBHeTAMun/VC2xatfltCssft95mYLjbw5Zk1yheyg2948T0AgILLh2OqobihJUOC5eP5MxhhjjCW3Jq0owdnCpjfbGzcNdsF1MXgIeChVOhmo6iLgDhG5CzgG+BdwAnA3cIWI3Ag8kagesKryEaJHV9rcrPU+jSYv+Kr4uHP+b0XM19UkO0tokuMS3cY5kJPtnuc3ElRdpwRgmrdAhTHGGBM3ltyatHJn73m/DplYsAo3uWuD9gflfT3tueUHq2pxFS/1laqGgcnAZBHpCNwCnIgbXb5cRP6hqnFvlxWGD2M1uz741C2+X/DV73NwE+XAtTyLLFvWlIr3ji28xyAVv/PcsnLNW1GuAHkr1m2oaa7MShKMMcbEnSW3Jr0Ih/55d2nONm1yNtq8dZucrFRNbCvzJpb1EpGDgduBw4GPROQ+4FpVXROvawXy1n7K+rwyYKOmtjvu1uisIRPaLgJdX8tTleO6SVQpVK5ZKBIK8cOYUxeMABZtXtTGGGNM1QRX9/arqrbyOxhjNpeIZAOjgIuPu2TrQIeum/RoLc1v3rrJsCPfbVBLvIqI4CbAjQZa4BY8GKiq0+J1jSGT2n4tyj7xOl/NdNqo3vMPTd71YhORabgOFjur6i9+x2OMMSY+bPld0+CJyA7Au8ClwIq8poHnYxyWs27VwnbJjaz+1HkU2BPX0aE18K6IXBiP81/yRvtmAjvG41y1J7ZggzHGmIQJAGEsyTUNlIj8Ddeb9lBgOtCp3f5Nnop1bCis9VqG10+q+ruq9sNNOAO4T0SeFJHGm3vO4e8dlZVbGnoBZav4RFlrsdrr+iHyvpcq8RhjjImDSFuknJoONCbViEhPYAqwHTAWOFxVf0YCc6p4QZUrlTUUqvp/wCG48oTBwJveKmt1tmbFwruAY+MYXm2lyshtZKJbwtqtGWOMSb4soBRLbk0DIyKnAf/DfUC7RFXvjexrMnPu/DX7FqwDNlqBQJQGO3IbTVVniMiBuCV8DwOmikgPVV1a23MUTmh7DsJFVVxhuSrvBiQQUHST4uUq44Jm4romVEuE72t7zgSz5NYYY9JQJLltUtOBxqQKETkXeBB3O/lMVR0bvX/YMA0XTmz7A9Cp0isb/MhthKouFpGjgVdxyw2/JyJHq+qfNb12yKS23UV4oIrdC8tEDry7d9HieMaboiLJbcJXgzPGGJM8AWA9kCsiNY64GOM3ETkeeADXempA5cS2gm5amiC6+/Dhkjb15aq6EldW8CbQAXhNRKr9oHrVpLa7ifI8sdsArkHodXevjEhswfXuDWHJrTHGpJUAsBTXEmxLn2Mxploish/wPO7v7Tmq+mJVx6pIrLrbvDX7tW6dqPj8oKrrgD7ANNzyws9V9UH1inGttgyHeYWKhReihQnooFG9imYlLtqU0xJYpqqpUgNsjDEmDiLJLbg3emNSkoi0wt2CzweuUdWYHRE2HK/h76K+XYfKlwJPSyg7bUZuI7zFKfoA84CeuIUfNnL+Q52zg9lZ4xDaxz4HQ0edOH9iYiNNHd4kvBwq3v+MMcakiSzgL++5JbcmJYlIANcNYXvgYVXdJHmrLLs0+6PynPAJGgjNyf9y4cJhwzSt2z2p6hIROQE3gnuliLyrqq9H9jfbdvm9IF1jvhb53+g+8+5IVqwpIvJ+91e1RxljjGlwsoAl3vNt/QzEmGoMBY4AvgMuqc0Lbu3/0xLAJXcnJiyulKKqP4jI2cAE4H8i0lFVFxdOancF6PkxXyR8VJoduCCpgaaGbbxHS26NMSbNBICfvedpVYto0oNXZzscKAZO8W7Bmyqo6kTgMWBr4MGhkwqOQ3VkFYfPzy4J9hvT46dMbIVV4D0u8DMIY4wx8Reg4s3dkluTUkREgP/D1UZerarf1fAS41wGzGvZKrt3eTkvEbv37CrCgV7eCHcmauM9LvAxBmOMMQkQndy28S8MY2I6FegCfA3cW8OxxqOqq3fYo/F1fa/dlmBQ8mIcEkJk4Ki+c79NenCpo433ON/PIIwxxsRfFm6GNRB7FrUxfhCRHOAm79tC1fSeEBZPw8d1yBl4+3YXVLnIrXDZqF7zXktqUKlnF++xyNcojDHGxF3AW7LzD2BXEWnkd0DGeM4H2gGvqupUv4NpSNbkrHsE5YiYO4VHR/Uqui/JIaWijkAZ8KPfgRhjjImvSM/PWbhR3D18jMUYYEPrr4u9b6/3M5aGZsjEttcAg2PtE2VKfrPWmdgZYSMisi2uW8IPqmqrkxljTJqJJLffeI8d/QrEmCg9cGUy76vq134H01AUTmzTVypKOTaycnF5STA7dMqwI98tT3ZcKSjyPvdNtUcZY4xpkCLJ7UzvcT+/AjEmykXeo90+r6UrJ7XpBIGxVPyb3qBkXTj04vA/cm/v+XMHH0JLRZH3uUxaatgYYzJG5D/CT7zHQ/0KxBgAEdka6A78hluMwNRg6OsF2wU0MBFoEmN32Wcvrbxn+W9lAKclN7KUFXmfm+ZrFMYYYxIiAKCqc3GTyvYVkXx/QzIZ7gRcX9ZJqmq30GtBy+RGoFXMffCvz19acTsQAk70egdnLO/nPxg3mWy6z+EYY4xJgOhbmJ/gJpV19ikWY8AltwCZ3qqq1kpyghejPLXJDuXO0b2LHlHVJcDnwA5Ap2THl2J2xa3e9qWqrvM7GGOMMfEXndx+5D129SMQY0QkCzgGWA+843M4DcaYHj+VjO4z/3TQq4FIP+DJC8vmD4067FXv8QQyW+T97QNfozDGGJMw0cntm97jcX4EYgywG9AM+NxG1epGUR3Ve/4IhVOAGcFSOfWF/hqKOiTyYeEAH8JLJT28xzerPcoYY0yDJaoVyxiJyEJgJ2B7Vf3Tt6hMRhKRAcAzwBhVvdTveBqq4cMlMGzYxiu6iUgTYBXwi6q28SUwn3mr3i0FBGipqiU+h2SMMSYBKrcNmuxtO8aHWIyx/qNxUDmxBVDVtcB8YGcRaZH8qFLCYUA+8I4ltsYYk74qJ7eRSTwnJTsQY4A9vUdLbhPjG9yoZaauRBh5X7PJisYYk8YqJ7dvAiuBHiLS3Id4TGbb2nv8zdco0lfk97p1tUelIREJ4pLbcmC8z+EYY4xJoI2SW+9W3UQgFzjRl4hMJot8oFrlaxTpa6X3mIkfXI8CtsGVJNh8AmOMSWObLNUJvOA9DkhmIMbgki4FVvsdSJrK5OT2FO9xnK9RGGOMSbhYye1bwGLgWBHZKcnxmMyWD6xV3XRClImLyIeGpr5GkWTeqoun4Ponv+hzOMYYYxJsk+RWVcuAJ3BLoJ6V9IhMJisBGvkdRBpr7D2u9zWK5DsVl9C/qKor/A7GGGNMYsUauQV4CHd7+B/eRAxjkmElkCUieX4HkqYi5Qgrqz0q/ZzrPT7qaxTGGGOSImZyq6rzgPeBVkDPpEZkMlkk6WrmaxTpK5LcZszopYgcABwI/IgtuWuMMRmhqpFbgHu8xyuTEYgxwHLvcStfo0hfLb3HTBq5HeI93q3RyzEaY4xJW9UltxOBOcBhInJQkuIxme1H73HPao8ym2sv7/F7X6NIEhFpA/QDlgFP+hqMMcaYpKkyufVGOcZ43w6p6jhj4iiyMlnHao8ydSYiWcDuwDJVzZRFMq4EsoD7veWHjTHGZIDqRm7BdU34A+grIvskIR6T2SLJ7d6+RpGe2uM6UczyO5Bk8NoYngusBe7zORxjjDFJVG1yq6rrgRHecTckIyCT0b4FQsCBIlLTBy9TN5HSooxIboFrccn8vbYimTHGZJbaJBAPAIuA3iKyf4LjMRlMVVcD04Btgc4+h5NuenmPb/gaRRJ4tbZn4xatGO1rMMYYY5KuxuRWVYuBWwABRiU8IpPpXvMeT/A1ijQiIrnA0bhb9O/5G01S3Ark4DokLPU7GGOMMclV21u/DwPfAUeJSN8ExmPMq97jib5GkV664lbomup9WE1bInIwbkWyxdiorTHGZKRaJbeqWg5c5n072hsJMibuVPU7XKuqTlYGEzeRFbpe8jWKBPPqtO/G3WW6WlVX+RySMcYYH9R60o6qTsXV67UFChMWkTHwX+/xYl+jSAMisjOu3vYvYJzP4STaOUAXYDrW19YYYzKW1GXRHhHZFZjpfdtJVTOiGbxJLhFpCvwK5AI722z3zScitwL/Bm5V1Wv9jidRRGR7YDZu6eZDVPUzn0Myxhjjkzq1W1LVH4GbcC12HrN2TSYRvK4JT+KS28tqONxUQUS2AM7HtVd70OdwEu1eoAWu9ZcltsYYk8HqNHILICLZwBfAPsBFqnp/IgIzmU1EdsQtxxsAdlfVhT6H1OCIyF24DwcPq+p5fseTKCJyEvAi8DPQwftwZIwxJkPVObkF8Cb6fAKUA51VdXa8AzNGRG4BrgGeUtXBfsfTkIhIW9xt+jJgV1X93eeQEsL7EDQT2BI4XlUn+xySMcYYn21WWYGqzgCGA42B50WkUVyjMsa5HdfS6TQROdTvYBqYe3BlHSPSOLEN4JYIbwncZ4mtMcYY2Mzk1nM78AHQAbgtPuEYU8G7vfxvXGunJ72JZqYGIvIPoCcwF7jD53ASqRC3OMW3wFCfYzHGGJMiNqssYcOLRVoDXwFbAKeq6vPxCsyYCBF5AegPPK6qZ/sdTyrzyhG+xt1VOVxVP/E5pIQQka7Am7iyiwNV9RufQzLGGJMi6tXtwJvkcwpuNvajItIhLlEZs7F/AX8AZ4nIAL+DSVVeedCzuNXIbk3jxLYV8ByQBVxoia0xxpho9W7lpapTgBuBJsBLIrJlvaMyJoqq/gWcifsQ9ZjV324qqv60C26y503+RpQYItIY1xlha+ABVX3c55CMMcakmHj1qb0ZeAXYFXjZluc18aaqbwJDcD2WJ3oLipgKtwEnAwuAvt6S2WnFS+DHUpHAX+pvRMYYY1JRXJJbVQ0DA3H1t0cAT4iIxOPcxkSo6t3AGNzs+Ne829MZT0Qux02oWo5rh7XY55ASZSRwEjAfl8CX+hyPMcaYFBS3FcZUdQ1uhvYvuDpc66BgEuEK4GVgF+ADEWnnczy+EpHrgDuB9UA/VZ3jc0gJISKXAlcCy0jvBN4YY0w9xXX5XFX9DTgBWAFc5f3Ha0zcqGoId/v9SaAN8JGIdPQ1KJ+IyHBcbe1aoJeqvudvRIkhIucAdwHFuBHb730OyRhjTAqrVyuwKk8qciAwBTdre6iqjor7RUxGE5Eg8ABwLrAKOFNVx/sbVXKISD7wCO4OyQrcSGa6dkY4CdcZQYGTVPUVn0MyxhiT4uI6chuhqp8BvXG3SkeIyGWJuI7JXN4I7nm4xUSaAi+KyA3epKO05U2k+xSX2C4EjkzjxHYgrrWZAKdZYmuMMaY2EpYIqOq7QF/crcS7ROT6RF3LZCZ1/o1b4GEtMAx4XUR28jeyxBCRwcAXwF64OyOdVXWmv1Elhoich+uMEMCNyo/zOSRjjDENREJHubz2TccDq4EbRWSkdVEw8aaqLwEHAt8DxwLficgF6fJ3TUR2FpHXcXXGTYFbgR5e/9+0IyKFuJKTcuAUVX3K55CMMcY0IAmpud3kIiL745bKbIlrwH66qq5P+IVNRhGRPNyCIpcBQeAD4JKGOropIjm41dluxCW1PwH/UNX3fQ0sQbw66ruAi4F1uBrbyf5GZYwxpqFJSnILICJ7Aa8BrYEPgT6quiwpFzcZRUT2xU242h83EelF4DpV/dHXwGrJqxs+CddOrx1uBPO/wDWqutbP2BJFRJrg6mtPBJYAvdO1ltgYY0xiJS25BRCR7XArmXUG5uL6ctq68CbuRCQb+CdwDbAtLkF8ErhHVWf5GVtVvKVlT8UtyLC7t/k1XFKbkjHHg4gUAC8BnYAfcd0f5vkblTHGmIYqqcktbBiheQrog5sEdJ6qPpPUIEzG8P6+XQRcBWzhbZ4BPASMTYXyGBFpi+v8cA6wlbd5GnBtuvaujRCRHrj3gy2B94C/q+pSX4MyxhjToCU9uQXwJvpcAwzH1UbeBxSqanHSgzEZQURaAGcDFwDtvc3LgFeBCcCbqrouifHsivuA1xfogpvcWebFcn+61tVGiEgWcD1wHe5nvxO4SlXLfQ3MGGNMg+dLcrvh4iJHAs8D2wCzcb0sv/YtIJP2vHrW7riShR5AjrdrHfAubsR0GjDdW1I6XtdtBxwMHAQcBewZtftn4HHgIW+Vv7QmIq1xbb4OA9YA56rq8/5GZYwxJl34mtwCeD1Jn8T9h18M/BsYo6phXwMzaU9EmuNa1fXFJbr5UbtDuA9cPwHzgSJgAbAY9/d0PbDcO7YR0BhX9tAIaAW0BQq8xw64D3DRZgPjgfGqOiO+P1nqEpEzgDFAM1x5yGmq+oO/URljzw7H7gAAA8FJREFUjEknvie3sKFM4RJgBJALfIkbzfnK18BMxhCRRriJjgcBh3iP28fp9GXATOAT4DPgY1VdEKdzNwgi0gbXu/ZYXAeLe3GlSKU+hmWMMSYNpURyG+G1cHoU2A8oxS2tensqTPoxmUdEtsWNvEa+CnCju1vgRmojX+uAFbjR3HXAb7iR3iLcqO88VS1JdvypwOtacTGuV28TXDeEf6jqB74GZowxJm2lVHILGyaaXAjcjEskfgWuxc1sT61gjTFVEpFuuEUZOuBasd0B3GATR40xxiRSyiW3EV57pDuB3t6mD3G3MT/zLypjTE1EpAOuxOh4b9O7uJXivvUvKmOMMZki4HcAVVHVIlXtAxwNzMLNrP5URKaISGd/ozPGVCYiBSLyIPA1LrH9BThDVbtaYmuMMSZZUnbkNppXqnAWrifmzrgJKZOAkao6zc/YjMl0IrIPMAQYgOtb/Sdu5Pb+TK01NsYY458GkdxGiEgucC5uAYgdvM2f4Gr5JqhqyK/YjPn/9u7nReY4juP4842ldhXZVU6aJEVJbTlIe0FSKKXkIvIXkH/DQbmy161Njmyb3LA3ZduDFFbUyo7Wb6ndt8P7/W3GZMvBfr/znXk96tt3ms9MvW/zns+P76uf5BNOjgPXiOcGAzSB68BNd/9WVW0iItLfatXcFvKxTReAq8DefPstMA6Mu/t8VbWJ9DIz2wFcJKKCi6S3eeAGcNvdv1RVm4iICNS0uS3k7NFJ4ApwBDBgBXgATBCzuUvVVShSf2Y2BJwGzhN7aQdy6AkRyHBHsbkiItItat3ctst408vAJVpbFn4B08Bd4L67L1RTnUi9mNkwsd3gLNHQDuZQk4jOveXucxWVJyIisqqeaW4LefjsKHAOOANsyyEnUqKmgIfAjJZQRYKZDQIHiRjsE0Ra2/oc/koc4JwEpnRITEREulnPNbftMh3pGHCK+MHe1Ta8DMwCj4CnxOPG5tz9e9l1ipQpD2buI8IVRoFDeR9o+9g74o/gPWLVQymBIiJSCz3d3HYysz1Etv0YcJjW9oXCChGZ+oKITX2d13tgkViSbWp/oXQrM1sHDAMjed9OxAY38r47rw0dX/0APCbCUqbdfbakkkVERP6rvmpuO5lZg5i1OgDsJ2aydv7DV5eBz/n6B6A4UanKRmAoX2/mz9nX1SwQqxbP8j7j7s/XpjwREZFy9XVz+zdmtoWY4SquBq1ZsBFga14GbKJ10EakKj+JP1kAS8AnYpVhkZiRfUOsQLwCXrr7xwpqFBERKcVvjzqbEE2Bc1YAAAAASUVORK5CYII=", + "text/plain": [ + "" + ] + }, + "metadata": {}, + "output_type": "display_data" + } + ], + "source": [ + "from IPython.display import Image, display\n", + "display(Image(filename='1_simple-PKRO_schematic.png'))" + ] + }, + { + "cell_type": "markdown", + "id": "f393aa69-7c07-4ef6-b9de-b9e76f18fa28", + "metadata": {}, + "source": [ + "This model is a three-compartment model with a central compartment (circulation), effect compartment (tissue/organ where the drugs target is expressed), and peripheral compartment (all other tissue/organs). \n", + "\n", + "The drug can distribute reversibly between each compartment and undergoes linear clearance from the central compartment. \n", + "\n", + "The drug targets a receptor expressed in the effect compartment through reversible binding to the receptor (or receptor occupancy). " + ] + }, + { + "cell_type": "markdown", + "id": "a34a5798-6ee6-4ee6-9a1c-2b14ebfa4ffa", + "metadata": {}, + "source": [ + "\n", + "## Building the model\n", + "\n", + "To build the model we'll use a combination of standard PySB model components:" + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "id": "5bb80984-8109-4bfc-ac64-dd8a3aee1b3f", + "metadata": {}, + "outputs": [], + "source": [ + "from pysb import Model, Monomer, Parameter, Observable, Initial, Expression, ANY, WILD" + ] + }, + { + "cell_type": "markdown", + "id": "67fd338d-e71e-4304-b72d-e7843d9896ad", + "metadata": {}, + "source": [ + "As well as one of the standard PySB macros:" + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "id": "3378c68b-4a0b-479c-9120-28c9432e9f82", + "metadata": {}, + "outputs": [], + "source": [ + "from pysb.macros import bind" + ] + }, + { + "cell_type": "markdown", + "id": "744d59c5-aa63-4696-8849-1df744eca794", + "metadata": {}, + "source": [ + "And macros from the `pysb-pkpd` add-on:" + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "id": "e60a18c3-60db-40c6-a861-4f40f8b23e13", + "metadata": {}, + "outputs": [], + "source": [ + "import pysb.pkpd as pkpd" + ] + }, + { + "cell_type": "markdown", + "id": "90ad547d-4ef1-4b83-ac7e-cce7d4a5947c", + "metadata": {}, + "source": [ + "Now, we can construct the model. We won't worry too much about the accuracy of the model parameters since this is just an example case: " + ] + }, + { + "cell_type": "code", + "execution_count": 5, + "id": "0594d1db-4b3e-4f35-aecf-f67476b719ad", + "metadata": {}, + "outputs": [ + { + "data": { + "text/latex": [ + "$\\displaystyle D_{E}$" + ], + "text/plain": [ + "Observable('D_E', Drug(b=None) ** EFFECT)" + ] + }, + "execution_count": 5, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "## Build the model.\n", + "# Initialize the PySB model.\n", + "Model()\n", + "# Define the Drug with one binding site.\n", + "Monomer(\"Drug\", ['b'])\n", + "# Alias the free drug.\n", + "free_drug = Drug(b=None)\n", + "# Define the target receptor with one binding site.\n", + "Monomer('Receptor', ['b'])\n", + "# Three-compartment model:\n", + "# c1 - CENTRAL (circulation)\n", + "# c2 - PERIPHERAL (other organs/tissue)\n", + "# c3 - EFFECT (effect site/organ/tissue)\n", + "# Each compartment is assumed to be 1 L.\n", + "pkpd.three_compartments(c3_name='EFFECT')\n", + "# Add a single Bolus dose of the Drug.\n", + "pkpd.dose_bolus(free_drug, CENTRAL, 200.) # mg\n", + "# Initialize the receptor in the EFFECT compartment.\n", + "Parameter('R_0', 0.1) # mg/L\n", + "Initial(Receptor(b=None)**EFFECT, R_0) \n", + "# Distribution/re-distribution:\n", + "# CENTRAL <-> PERIPHERAL\n", + "pkpd.distribute(free_drug, CENTRAL, PERIPHERAL, [0.01, 0.05]) # mg/minute\n", + "# CENTRAL <-> EFFECT\n", + "pkpd.distribute(free_drug, CENTRAL, EFFECT, [0.025, 0.011])\n", + "# Clearance of the drug from the CENTRAL compartment.\n", + "pkpd.clearance(free_drug, CENTRAL, 1e-1) # L/minute\n", + "# Binding of the Drug to the Receptor - i.e., recptor occupancy.\n", + "bind(free_drug**EFFECT, 'b', Receptor(b=None)**EFFECT, 'b', [3e-4, 1e-4])\n", + "# Define the model observables:\n", + "# Receptor-Drug complex and occupancy.\n", + "Observable('Rbound', Receptor(b=ANY)**EFFECT)\n", + "Observable('Rtotal', Receptor(b=WILD)**EFFECT)\n", + "Expression('RO', Rbound / Rtotal)\n", + "# Free drug in each compartment.\n", + "Observable('D_C', free_drug**CENTRAL)\n", + "Observable('D_P', free_drug**PERIPHERAL)\n", + "Observable('D_E', free_drug**EFFECT)" + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "id": "9edb8acf-3b9e-489f-9e8b-151d79cd243d", + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "" + ] + }, + "execution_count": 6, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "model" + ] + }, + { + "cell_type": "markdown", + "id": "bcddde04-027e-4185-b39d-2d9e739e79f8", + "metadata": {}, + "source": [ + "### Simulating the model" + ] + }, + { + "cell_type": "code", + "execution_count": 7, + "id": "f7f5c345-998c-4111-b5d6-aced60f6ed0a", + "metadata": {}, + "outputs": [], + "source": [ + "from pysb.simulator import ScipyOdeSimulator\n", + "import numpy as np\n", + "import matplotlib.pyplot as plt" + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "id": "213f8df3-860a-43f5-be66-92b3fccbe6a2", + "metadata": {}, + "outputs": [], + "source": [ + "tspan = np.arange(0, 60*48) # minutes" + ] + }, + { + "cell_type": "code", + "execution_count": 9, + "id": "eaf52a84-45b3-4521-9e21-64e960f872e3", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Simulating...\n" + ] + } + ], + "source": [ + "print(\"Simulating...\")\n", + "yfull = ScipyOdeSimulator(model).run(tspan=tspan).all" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "id": "705128bf-3116-4828-ace6-7285871b6e9b", + "metadata": {}, + "outputs": [], + "source": [ + "tspan_hr = tspan / 60" + ] + }, + { + "cell_type": "markdown", + "id": "51cb5422-44c5-4951-9649-aeda0cb06eb1", + "metadata": {}, + "source": [ + "#### PK data" + ] + }, + { + "cell_type": "code", + "execution_count": 11, + "id": "8075b78c-42b1-41a1-b6c9-21b08daa51ea", + "metadata": {}, + "outputs": [ + { + "data": { + "image/png": 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", + "text/plain": [ + "
" + ] + }, + "metadata": {}, + "output_type": "display_data" + } + ], + "source": [ + "plt.plot(tspan_hr, yfull['D_C'], label='CENTRAL')\n", + "plt.plot(tspan_hr , yfull['D_P'], label='PERIPHERAL')\n", + "plt.plot(tspan_hr , yfull['D_E'], label='EFFECT')\n", + "plt.ylabel(\"Concentration (mg/L)\")\n", + "plt.xlabel(\"Time (hr.)\")\n", + "plt.legend(loc='upper left')\n", + "plt.show()" + ] + }, + { + "cell_type": "markdown", + "id": "75f1899f-66ed-4929-8d41-24bf00dfc787", + "metadata": {}, + "source": [ + "#### Receptor occupancy (RO)" + ] + }, + { + "cell_type": "code", + "execution_count": 12, + "id": "3a25814e-69b7-4b24-bca8-7394f2cb8549", + "metadata": {}, + "outputs": [ + { + "data": { + "image/png": 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xQofrtKe8XmU1DSc9LzYi1D026MQWoeyUGIUzAB5AgLX71hLLli3T5MmTNWnSJGVmZrb6nt69e2v58uU+F4Mz19Bk129f3Spro10j+qbo4Z+ca3ZJ6GAsFovSE6KUnhClEf1SPV6rbWjS3pYxQidOoy+utKq+0a7t33lvxhoWYlF2SozHOCHnStaxSoiiewxAx8DCg0Fmwbs7teKTIqXERui96SOVHt+5lg1Ax9TY7FDJEe9p9HsO18naaD/peenxkce32Ug7vuUGs8cA+KrdW3hWrlypuLg4/fznP/c4vnr1almtVk2cONHnIuAfm/ZWasUnRZKkx38+mLADv4kIC1G/9Hj1S4/3OO5wGCqrafAcI9Sy5UZ5rc392LT3iMd5UeEhyjlxz7GWrzmp7EgPIDB8/pdl0aJFeu6557yOp6en68477yTwmMTWbNect3ZIkm69sLdG9c8wuSJ0BSEhFmUlRSsrKVqXnu25HEVNS/fYnvI67a1wjhHa09I91tDkUGFpjXs/txNlJUYpN+34KtOuliEGTQM4Ez4HnuLi4la3lsjOzlZJSYlfioLv/rR2r/YcrldqXKQe/HF/s8sBlBAVrvN6Jem8Xkkex5vtDn139Ji7JWjPCRuxVtY36mB1gw5WN2jD7gqP82IjQt1jg1xdZH3TY9UnJVZR4awpBODUfA486enp2r59u/r06eNx/KuvvlJKSoq/6oIPvjtq1TMf7ZYkPXLtuayjgg4tLDREfVJj1Sc1VlcM8HztaH2jszXIFYTKnTvTFx9xDprecaBaOw54Dpq2WKSe3ZxbbuSmOkOQq1WIHekBuPgceG6++Wbdc889io+P16WXXipJWrt2re69917dfPPNfi8QP2xxwb/V2OzQRbnJunZwx1vsEWirbrERyo9NVn52ssdx56Bpq1er0J7yOtU0NGv/kWPaf+SYPt512OO8+Kgwj8HSzllkseqdHKuIMKbSA12Jz4Hn0UcfVXFxsa644gqFhTlPdzgcmjBhgv7whz/4vUCcWmFpjd7aekCSNGvsAP5vFkHJOWjaOeX9RIZhqLK+sWWckHO80J7Dzu/3H7GqtqFZ2/ZXadv+Ko/zQkMs6p0co75pscfHC6U5p9OzESsQnE57Wvq///1vffXVV4qOjtagQYOUnZ3t79oCItimpU9a+bk+2nVY1wzurmdvHWp2OUCH0dBkV3Glq1XoeDfZ3sP1qjvFStPdYsKdY4VSY5WTFqvcltlk2SnsPwaYyfS9tDqbYAo8O76r1rXPbFBoiEX/mHmZclJjzS4J6PAMw1B5rc3ZGnRiq9Dh+lNuxBpikXp0i1ZuqnP6fN+0WPfU+syEKNYVAgKs3dfhsdvtevHFF/Xhhx+qvLxcDofD4/V//vOfPheB0/Pc2j2SpOuGZBF2gDayWCzKSIhSRisrTVsbm1VUUa+9h+tbvta5n9fajo8VWvtvz7FC0eGh6pMaq9zUWOWmxSon1dlVlpMayyQCoIPwOfDce++9evHFF3XNNdcoLy+PMSMmKaqo15qvSyVJv74s1+RqgOAQExGmgVmJGpiV6HHcMAxV1DUeD0AtIWhvRZ1KKq061mQ/6bpCqXERzgCUGtfSReYMRQycBtqXz4Hntdde01//+lddffXVgagHbfT8ur0yDGlU/3T1z+zcXXNAR2exWJQWH6m0+EhdmOu5/IZrV/qiirqWEHS8ZehQjU0VdY2qqGvUF/uOepwXYpF6Jcc4xwq1dI3ltrQMZSQwnR7wN58DT0REhPr16xeIWtBG1dYmvfnld5KkqZf1NbkaoGsLCw1RTqqzG2vU99b8rLM1a1+Fc7D097vK6hudg6qLK6366HvT6WMiQt3XdA2gdnWVxbMhK3BafA489913n5588kk988wz/B+ISd748jvZmh3qnxmv/+jTzexyAJxEXGSY8nokKq+HdxfZ4Vqb9nx/rFBFvUqOWGVttOubgzX65qB3F1lafOQJg6aPd5X1To5ReChdZMDJ+Bx4NmzYoI8++kjvvfeeBg4cqPBwz//bePPNN/1WHLwZhqFXPiuWJP3yomxCJ9AJWSwWpSdEKT0hSsP7enaRNdmdiywWtYwRKqqodwejw7U29+PzIs8NWV1rC+W2tAzlpMUqJ8W5ojWzyIDTCDxJSUn66U9/Goha0Aab9h7RnsP1io0I1fXn9zC7HAB+Fh4a4l4VWvLcBLimoUn73AOmj7cMFVXUy9pod3//fVHhIeqT4tx3zDWbzLm9Rwzbb6DL8DnwrFy5MhB1oI3+unm/JGnc+T0UF+nzHx+ATiwhKlyDeyZpcM8kj+OGYehQjU17W1aZ3nu4Xvsq67WvpYusocmhf5XV6l9ltV7XjIsMU5/UGPVJOTEIOb9PimHVaQQPfmN2ItbGZv39mzJJ0o35PU2uBkBHYbFYlJkYpcxE77WFXLvTF7UEIFcr0L7Ken139JjqbM36+kCNvj7gPV4oKSbcKwg5u8liGDyNTue0As/rr7+uv/71ryopKVFjY6PHa19++aVfCoO3gp2HZG20KzslRuf3SjK7HACdwIm70+scz9dszXbtP2JVUYVVRRV1KqqwukNRWU2DqqxN2mb13otMklLjIpWTGqOcE4JQTpqz2ywqnC040PH4HHieeuopzZkzRxMnTtTbb7+tSZMmac+ePfriiy80bdq0QNSIFn9r2SR03JAs+twBnLHIsFD1S49Xv/R4fX+8kLWxWcWV1uMtQie0DDnXFrKpos7mtb6QJHVPjPIMQi3f906OYbFFmMbnvbT69++vuXPn6pZbblF8fLy++uor5ebm6pFHHtGRI0f0zDPPBKpWv+ise2lV1tl0wR8+lN1h6MP7LmsZ0AgA7c81eNoZhFpahyqtKjpcp5qGk2/MGmKRenaLaQlCLV9bHj2SohXGtHqcQrvvpVVSUqIRI0ZIkqKjo1Vb6xwEd9ttt+miiy7q8IGns/pg5yHZHYbyeiQQdgCY6lSDp49amzxahE4cO2RttKvkiFUlR6xa971rhoda1Cs5xj2VPifV2T2WnRKjrKRohTKtHmfI58CTmZmpyspKZWdnKzs7W5s2bdKQIUNUVFSk09l4fenSpXr88cdVWlqqgQMHasmSJRo5cuRJ32+z2bRgwQL95S9/UVlZmXr27Kk5c+Zo8uTJPn92Z1Kw85Ak6ccDM02uBABaZ7FYlBwboeTYCOVney6K6lpssaiVILSv0qrGZodzuv1h72n1EaEh6pUc3RKAnIOms1Oc3WVZSVG0DKFNfA48o0aN0rvvvquhQ4dqypQpmjFjhl5//XVt3rxZN9xwg0/XWrVqlaZPn66lS5fq4osv1p/+9CeNHTtWO3fuVO/evVs956abbtKhQ4e0fPly9evXT+Xl5WpuPnkTajCotzVrw+4KSdIYAg+ATujExRa/vx+Zw2GotKbBucZQS+vQvpbxQvuPHFOj3aE9h50LMH5fWIizZSg7JcbdItSnpXWoZ7doVp+Gm89jeBwOhxwOh8LCnFnpr3/9qzZs2KB+/fpp6tSpioho+7oNF154oYYOHaply5a5jw0YMEDXX3+9Fi5c6PX+999/XzfffLP27t2r5ORkX8p264xjeN7bUarfvPKlslNi9PH9lzNgGUCXYXcYKq0+pn0VVu2rrFdxpbNFqLiyXsWVVtmaHSc9NzTEoh5J0e4w5AxCztahXsnRigxjNlln0u5jeEJCQhQScjwx33TTTbrpppt8/uDGxkZt2bJFDz30kMfxMWPGaOPGja2e884772jYsGF67LHH9PLLLys2NlbXXXedfv/73ys6OrrVc2w2m2w2m/t5TY33WhMdnas7a/SADMIOgC4lNMSint1i1LNbjC45y3ONIYfDUFlNQ0sQaglE7mBk1bGm42OG1n9b4XGuxSJlJUa7F108sXWod3IMU+uD0Gmtw3P06FEtX75chYWFslgsGjBggCZNmuRTq0tFRYXsdrsyMjynQmZkZKisrKzVc/bu3asNGzYoKipKb731lioqKnTXXXfpyJEjWrFiRavnLFy4UPPnz2/7D9fBNNsd+ueuckl0ZwHAiUJCLMpKilZWUrRG9PV8zTAMldfatK/ihDDU8nVfRb3qG+06UHVMB6qO6ZPdlV7X7p4Y1dIq5GwRcrUMZafEKCaCNXs7I5//1NauXatx48YpISFBw4YNk+Rcm2fBggV65513dNlll/l0ve+3WBiGcdJWDIfDIYvFoldeeUWJic7dhxcvXqwbb7xRzz77bKutPLNmzdLMmTPdz2tqatSrVy+fajTTjgPVqrI2KSEqTEN7J5ldDgB0ChaLRRkJUcpoZcyQYRiqqGv06B5zfS2qqFdtQ7NKqxtUWt2gT/d6h6GMhEiPEHRi6xBb/nRcPv/JTJs2TTfddJOWLVum0FBnk5/dbtddd92ladOm6euvv27TdVJTUxUaGurVmlNeXu7V6uPSvXt39ejRwx12JOeYH8Mw9N133+mss87yOicyMlKRkZFt/fE6nA0tzbAj+qYyEwEA/MBisSgtPlJp8ZEa1sezZ8I1td49XqiiJQi1BKIqa5MO1dh0qMZ7x3rJuQL18SAUo+zUWGW3DKpmbzJz+Rx49uzZozfeeMMddiQpNDRUM2fO1EsvvdTm60RERCg/P18FBQUeu68XFBRo3LhxrZ5z8cUXa/Xq1aqrq1NcnHMtmn//+98KCQlRz57BubfU+pbZWd/vuwYA+N+JU+uH9u7m9XqVtdGzi6xlNllxpVWV9cdXoN5c7L0CdUJUmLJTYtU7JcYdgnonO1uHMhOiFMJaQwHlc+AZOnSoCgsLdc45npuyFBYW6rzzzvPpWjNnztRtt92mYcOGafjw4Xr++edVUlKiqVOnSnJ2Rx04cMAdpG699Vb9/ve/16RJkzR//nxVVFTogQce0OTJk086aLkzq7c1a2uJ8z+akQQeADBdUkyEkmIiNKSV/QxrGppUckIYKqqod88mK6+1qaahWTsOVGvHgWqvcyPCQtSrW7QzELWEIVcgYkaZf/gceO655x7de++92r17ty666CJJ0qZNm/Tss89q0aJF2r59u/u9gwcPPuW1xo8fr8rKSi1YsEClpaXKy8vTmjVrlJ2dLUkqLS1VSUmJ+/1xcXEqKCjQb3/7Ww0bNkwpKSm66aab9Oijj/r6Y3QKnxVVqsluqFey8z8CAEDHlRAVrrweicrrkej12rGWVaaLK+tbvlpVfMSqkpZd6xubT77WkMUidU+IamkZamkhOuH7xGh2rm8Ln9fhOXFKeqsXtFjcA4/tdvsZFRcInWkdnvnvfqOVn+zTLRf01sIbBpldDgAgAJrtDpVWN7SEoHqVVHoGovrGU/8uTYoJV3ZyjHqnxLZ8dXWZxSo9PjJousrafR2eoqIinz8Ep+fTPc7ZARf3S/mBdwIAOquw0BD1So5Rr+QYXSLP4QuGYaiy3jluqOSIs3uspCUMFVdaVVFnU5W1SVXWan31nXdXWWRYiLuLzDVeyBWIenbrWrvX+xx4XN1NCKyahibtOuTcmPWCPqe3qjQAoHOzWCxKjYtUalyk1/5kklRna1bJCWHI2SrkbCk6WNUgW7ND35bX6dvyOq9zQyxS98Roj/FCzq/O5/FRwdVV5nPg+aGZWBMmTDjtYnDcl8VHZRhS7+QYpSdEmV0OAKADiosM07lZCTo3y7uLp8nu0IGjx9xdYycGopIjzpWoXYsvbtzjvd5QcmzE8QHUri6zlkCUFtf5usp8Djz33nuvx/OmpiZZrVZFREQoJiaGwOMnm/c5Z2cN6+Od6AEA+CHhoSHO/cNSYyWlebzm2r3e1TVWUll//PsjVh2pb3Q/tu2v8rq2q6usd0tX3IktQz27dcytOXwOPEePeq8t8O233+o3v/mNHnjgAb8UBWlzsXNBq2HZdGcBAPzrxN3r/6OVYRO1DU3u8OMaP+T6/mDVsVN2lUlSr+RorXvgRx1q/0e/rIF91llnadGiRfrlL3+pf/3rX/64ZJfWZHe4E/V/0MIDAGhn8aeYYt9kd+hg1TF3INp/QstQyRGr6mzNCg8J6VBhR/JT4JGcqy0fPHjQX5fr0r45WKOGJoeSYsLVNy3O7HIAAHALDw1p2UjVe30419YcR62NJlR2aj4HnnfeecfjuWEYKi0t1TPPPKOLL77Yb4V1ZZv3Obuz8nt363SDwgAAXdeJW3N0ND4Hnuuvv97jucViUVpamkaNGqUnnnjCX3V1aa5lx89rZelyAADgO58Dj8PhCEQdOMGOlsWj8np6950CAADfdZ0lFjuJ2oYm7a1w7qUyqJXBYgAAwHc+B54bb7xRixYt8jr++OOP6+c//7lfiurKvjlYI0nKSoxSalykydUAABAcfA48a9eu1TXXXON1/Mc//rHWrVvnl6K6Mld31iC6swAA8BufA09dXZ0iIrxHX4eHh6umpsYvRXVlrgHLdGcBAOA/PgeevLw8rVq1yuv4a6+9pnPPPdcvRXVl7sDTM8ncQgAACCI+z9J6+OGH9bOf/Ux79uzRqFGjJEkffvihXn31Va1evdrvBXYlNQ1NKmLAMgAAfudz4Lnuuuv0t7/9TX/4wx/0+uuvKzo6WoMHD9Y//vEPXXbZZYGoscv4V2mtJOeA5Y64aBMAAJ3VaW0tcc0117Q6cBlnZleZcwxU/+4JJlcCAEBw8XkMzxdffKHPPvvM6/hnn32mzZs3+6WormrXIWcLzzmZ8SZXAgBAcPE58EybNk379+/3On7gwAFNmzbNL0V1VbvKWgJPBoEHAAB/8jnw7Ny5U0OHDvU6fv7552vnzp1+KaorMgzjeOChhQcAAL/yOfBERkbq0KFDXsdLS0sVFnZaQ4IgqaymQTUNzQoNsSg3LdbscgAACCo+B57Ro0dr1qxZqq6udh+rqqrS7NmzNXr0aL8W15W4WndyU2MVGRZqcjUAAAQXn5tknnjiCV166aXKzs7W+eefL0natm2bMjIy9PLLL/u9wK7CFXjOpjsLAAC/8znw9OjRQ9u3b9crr7yir776StHR0Zo0aZJuueUWhYeHB6LGLsE1Q6s/A5YBAPC70xp0ExsbqzvvvNPftXRpu8vrJElnEXgAAPA7n8fwrF69WjfccIPy8vI0aNAg3XDDDXr99dcDUVuXYRiG9h52binRlwHLAAD4XZsDj8Ph0Pjx4zV+/Hjt3LlT/fr1U25urr755hvddNNNuvnmm2UYRiBrDVqHa22qszUrxCL1TokxuxwAAIJOm7u0lixZon/84x9655139JOf/MTjtXfeeUeTJk3Sk08+qenTp/u7xqC3t2XD0F7JMczQAgAgANrcwvPiiy/q8ccf9wo7knND0ccee0zLly/3a3Fdhas7KyeV7iwAAAKhzYHn22+/1ZVXXnnS16+88krt3r3bL0V1NXsPOwcs56bGmVwJAADBqc2BJzo6WlVVVSd9vaamRtHR0f6oqcspaunSYoVlAAACo82BZ/jw4Vq2bNlJX3/22Wc1fPhwvxTV1bjG8OTSpQUAQEC0edDynDlzdPnll6uyslL333+/+vfvL8MwVFhYqCeeeEJvv/22Pvroo0DWGpQamx0qOWKVJOWm0aUFAEAgtDnwjBgxQqtWrdKdd96pN954w+O1bt266dVXX9XFF1/s9wKD3f6jVtkdhmIiQpWREGl2OQAABCWfVlr+6U9/qquuukp///vf9e2330qSzj77bI0ZM0YxMawfczqKTpihZbFYTK4GAIDg5PPWEjExMfrpT38aiFq6JFd3VjYLDgIAEDA+by0B/3IFnl7dCDwAAAQKgcdk3x1tCTzJBB4AAAKFwGMydwsPgQcAgIDxKfA0Nzfrz3/+s8rKygJVT5diGIb2HzkmSerVjUUbAQAIFJ8CT1hYmH7zm9/IZrMFqp4upbK+Ucea7LJYpB4EHgAAAsbnLq0LL7xQ27ZtC0ApXY+rOyszIYpd0gEACCCfp6Xfddddmjlzpvbv36/8/HzFxnpuhzB48GC/FRfs9jNDCwCAduFz4Bk/frwk6Z577nEfs1gsMgxDFotFdrvdf9UFuf0MWAYAoF34HHiKiooCUUeX5B6wnMz4HQAAAsnnwJOdnR2IOrok1xie3rTwAAAQUD4HHknas2ePlixZosLCQlksFg0YMED33nuv+vbt6+/6gtp3VXRpAQDQHnyepfX3v/9d5557rj7//HMNHjxYeXl5+uyzzzRw4EAVFBQEosag5HAYKqtukCRlJdGlBQBAIPncwvPQQw9pxowZWrRokdfxBx98UKNHj/ZbccGsos6mJruhEIuUER9pdjkAAAQ1n1t4CgsLNWXKFK/jkydP1s6dO/1SVFdQ2tK6kx4fpbBQdvgAACCQfP5Nm5aW1urCg9u2bVN6ero/auoSSqudM7QyE6NMrgQAgODnc5fWr371K915553au3evRowYIYvFog0bNuiPf/yj7rvvvkDUGJQOVrnG7xB4AAAINJ8Dz8MPP6z4+Hg98cQTmjVrliQpKytL8+bN81iMEKfmauHpnsiAZQAAAs3nwGOxWDRjxgzNmDFDtbW1kqT4+Hi/FxbsXGN4utOlBQBAwPk8hmfUqFGqqqqS5Aw6rrBTU1OjUaNG+bW4YFbKlHQAANqNz4Hn448/VmNjo9fxhoYGrV+/3i9FdQWlVQxaBgCgvbS5S2v79u3u73fu3KmysjL3c7vdrvfff189evTwb3VByu4wdKjWJknKYgwPAAAB1+bAc95558lischisbTadRUdHa2nn37ar8UFq8O1NtkdhsJCLEpj0UEAAAKuzYGnqKhIhmEoNzdXn3/+udLS0tyvRUREKD09XaGhoQEpMtgcbJmhlZEQpdAQi8nVAAAQ/NoceFy7pDscjoAV01WUVjFDCwCA9nRau6Xv2rVLTz/9tHu39P79++vuu+9W//79/V1fUGKVZQAA2pfPs7Ref/115eXlacuWLRoyZIgGDx6sL7/8UoMGDdLq1asDUWPQOdwyYDkjgcADAEB78Dnw/O53v9OsWbP06aefavHixVq8eLE2btyo2bNn68EHH/S5gKVLlyonJ0dRUVHKz89v89T2Tz75RGFhYTrvvPN8/kyzlbcEnnQGLAMA0C58DjxlZWWaMGGC1/Ff/vKXHlPV22LVqlWaPn265syZo61bt2rkyJEaO3asSkpKTnledXW1JkyYoCuuuMKnz+soXC08zNACAKB9+Bx4Lr/88lZbYTZs2KCRI0f6dK3FixdrypQpuuOOOzRgwAAtWbJEvXr10rJly0553q9//WvdeuutGj58uE+f11GU1zoHLafH06UFAEB78HnQ8nXXXacHH3xQW7Zs0UUXXSRJ2rRpk1avXq358+frnXfe8XjvyTQ2NmrLli166KGHPI6PGTNGGzduPOl5K1eu1J49e/SXv/xFjz766A/Wa7PZZLPZ3M9ramp+8JxAc3dpJdDCAwBAe/A58Nx1112SnGNvli5d2uprknOTUbvdftLrVFRUyG63KyMjw+N4RkbGSbvGvv32Wz300ENav369wsLaVvrChQs1f/78Nr23Pdia7aqyNkmS0uIIPAAAtAefu7QcDkebHqcKOyeyWDwX3jMMw+uY5Ny+4tZbb9X8+fN19tlnt7neWbNmqbq62v3Yv39/m88NhIo65z5kEaEhSooJN7UWAAC6itNah8eloaFBUVGnNw4lNTVVoaGhXq055eXlXq0+klRbW6vNmzdr69atuvvuuyU5w5dhGAoLC9MHH3zQ6pYXkZGRiozsOC0p5TXO8Ttp8ZGtBjsAAOB/Prfw2O12/f73v1ePHj0UFxenvXv3SpIefvhhLV++vM3XiYiIUH5+vgoKCjyOFxQUaMSIEV7vT0hI0I4dO7Rt2zb3Y+rUqTrnnHO0bds2XXjhhb7+KKZwjd9JZYYWAADtxufA85//+Z968cUX9dhjjykiIsJ9fNCgQXrhhRd8utbMmTP1wgsvaMWKFSosLNSMGTNUUlKiqVOnSnJ2R7mmwIeEhCgvL8/jkZ6erqioKOXl5Sk2NtbXH8UUh1mDBwCAdudzl9ZLL72k559/XldccYU7mEjS4MGD9a9//cuna40fP16VlZVasGCBSktLlZeXpzVr1rj37SotLf3BNXk6GxYdBACg/fkceA4cOKB+/fp5HXc4HGpqavK5gLvuustjdteJXnzxxVOeO2/ePM2bN8/nzzTT4drjY3gAAED78LlLa+DAga0uPLh69Wqdf/75fikqmB3v0mLRQQAA2ovPLTxz587VbbfdpgMHDsjhcOjNN9/Url279NJLL+l///d/A1FjUKFLCwCA9udzC8+1116rVatWac2aNbJYLHrkkUdUWFiod999V6NHjw5EjUGlvIZ9tAAAaG+ntQ7PVVddpauuusrftQQ9h8NQRR3bSgAA0N58buH54osv9Nlnn3kd/+yzz7R582a/FBWsahqa1OwwJEnJsRE/8G4AAOAvPgeeadOmtbo9w4EDBzRt2jS/FBWsKuud20rER4UpMizU5GoAAOg6fA48O3fu1NChQ72On3/++dq5c6dfigpWlS37aKXQugMAQLvyOfBERkbq0KFDXsdLS0vbvIN5V3Wk3jl+h+4sAADal8+BZ/To0e4dyF2qqqo0e/ZsZmn9AFeXVnIsA5YBAGhPPjfJPPHEE7r00kuVnZ3tXmhw27ZtysjI0Msvv+z3AoPJEbq0AAAwhc+Bp0ePHtq+fbteeeUVffXVV4qOjtakSZN0yy23KDw8PBA1Bg13C08cgQcAgPZ0WoNuYmNjdeedd/q7lqDnCjy08AAA0L58HsMjSS+//LIuueQSZWVlqbi4WJL03//933r77bf9WlywcQ1aTqGFBwCAduVz4Fm2bJlmzpypsWPH6ujRo7Lb7ZKkbt26acmSJf6uL6i4pqUzaBkAgPblc+B5+umn9f/+3//TnDlzPKahDxs2TDt27PBrccHmCF1aAACYwufAU1RU5J6ddaLIyEjV19f7pahgZBiGO/CwDg8AAO3L58CTk5Ojbdu2eR1/7733dO655/qjpqBUc6yZfbQAADCJz7O0HnjgAU2bNk0NDQ0yDEOff/65Xn31VS1cuFAvvPBCIGoMCpUtA5bjIsMUFc4+WgAAtCefA8+kSZPU3Nys3/3ud7Jarbr11lvVo0cPPfnkk7r55psDUWNQoDsLAADznNY6PL/61a/0q1/9ShUVFXI4HEpPT5fk3DG9R48efi0wWFQSeAAAMM1prcPjkpqaqvT0dJWVlem3v/2t+vXr56+6gg4ztAAAME+bA09VVZV+8YtfKC0tTVlZWXrqqafkcDj0yCOPKDc3V5s2bdKKFSsCWWunRpcWAADmaXOX1uzZs7Vu3TpNnDhR77//vmbMmKH3339fDQ0Neu+993TZZZcFss5Oz73oIKssAwDQ7toceP7v//5PK1eu1JVXXqm77rpL/fr109lnn83qym1UZW0JPDEEHgAA2lubu7QOHjzoXmcnNzdXUVFRuuOOOwJWWLCpOtYkSUqKYUd5AADaW5sDj8PhUHj48V/WoaGhio2NDUhRwcjVwpMYTQsPAADtrc1dWoZh6Pbbb1dkpHPjy4aGBk2dOtUr9Lz55pv+rTBI0MIDAIB52hx4Jk6c6PH8l7/8pd+LCWbVVgIPAABmaXPgWblyZSDrCGqGYbhbeLoxaBkAgHZ3RgsPom3qbM2yt2wcmhhNCw8AAO2NwNMOqlq6s6LCQ9g4FAAAExB42oEr8CQxQwsAAFMQeNpB1THnlHQGLAMAYA4CTztwtfAwfgcAAHMQeNoBa/AAAGAuAk87qG5ZZZkxPAAAmIPA0w6qWHQQAABTEXjagatLK5HAAwCAKQg87cDVwsMqywAAmIPA0w6qXdPSmaUFAIApCDztwD0tnS4tAABMQeBpB+5p6czSAgDAFASeADMMQ1VWVloGAMBMBJ4Aszba1WR37pRO4AEAwBwEngBzdWdFhIYomp3SAQAwBYEnwGpaAk9CdJgsFovJ1QAA0DUReAKsztYsSYqPojsLAACzEHgCrK7BGXjiIsNMrgQAgK6LwBNgNQ3OLi0CDwAA5iHwBNjxLi0CDwAAZiHwBJi7S4vAAwCAaQg8AVbbEnji6dICAMA0BJ4AY5YWAADmI/AEWC1dWgAAmI7AE2B1NmZpAQBgNgJPgLnH8NDCAwCAaQg8Aca0dAAAzEfgCbDjKy0zaBkAALMQeAKshi4tAABMR+AJMAYtAwBgPgJPADXZHWpockiihQcAADMReALINX5HooUHAAAzEXgCyDVDKzo8VGGh3GoAAMxi+m/hpUuXKicnR1FRUcrPz9f69etP+t4333xTo0ePVlpamhISEjR8+HD9/e9/b8dqfcMqywAAdAymBp5Vq1Zp+vTpmjNnjrZu3aqRI0dq7NixKikpafX969at0+jRo7VmzRpt2bJFP/rRj3Tttddq69at7Vx529Q2OAcsM34HAABzWQzDMMz68AsvvFBDhw7VsmXL3McGDBig66+/XgsXLmzTNQYOHKjx48frkUceadP7a2pqlJiYqOrqaiUkJJxW3W31YeEhTfnzZg3pmai3774koJ8FAEAwO9Pf36a18DQ2NmrLli0aM2aMx/ExY8Zo48aNbbqGw+FQbW2tkpOTT/oem82mmpoaj0d7cY3hoUsLAABzmRZ4KioqZLfblZGR4XE8IyNDZWVlbbrGE088ofr6et10000nfc/ChQuVmJjofvTq1euM6vaFe9FBVlkGAMBUpg9atlgsHs8Nw/A61ppXX31V8+bN06pVq5Senn7S982aNUvV1dXux/79+8+45raqY9AyAAAdgmm/iVNTUxUaGurVmlNeXu7V6vN9q1at0pQpU7R69WpdeeWVp3xvZGSkIiMjz7je08EqywAAdAymtfBEREQoPz9fBQUFHscLCgo0YsSIk5736quv6vbbb9f//M//6Jprrgl0mWfENS09gRYeAABMZepv4pkzZ+q2227TsGHDNHz4cD3//PMqKSnR1KlTJTm7ow4cOKCXXnpJkjPsTJgwQU8++aQuuugid+tQdHS0EhMTTfs5ToYuLQAAOgZTfxOPHz9elZWVWrBggUpLS5WXl6c1a9YoOztbklRaWuqxJs+f/vQnNTc3a9q0aZo2bZr7+MSJE/Xiiy+2d/k/qNY1S4tBywAAmMrUdXjM0J7r8Nz8/KfatPeInrrlfF03JCugnwUAQDDrtOvwdAWudXhYaRkAAHMReAKozr0OD4EHAAAzEXgCiM1DAQDoGAg8AVTr7tJi0DIAAGYi8ASIrdmuxmaHJBYeBADAbASeAHGN35EIPAAAmI3AEyCuGVqxEaEKDfnhvcEAAEDgEHgChAHLAAB0HASeAHEHHrqzAAAwHYEnQOqYoQUAQIdB4AmQOluTJFZZBgCgIyDwBAhdWgAAdBwEngBxBR5aeAAAMB+BJ0BcY3jiIhnDAwCA2Qg8AVLb4BzDw7R0AADMR+AJENdKywkEHgAATEfgCZDjXVoEHgAAzEbgCZAaVloGAKDDIPAESF0DCw8CANBREHgChC4tAAA6DgJPgLhmabEODwAA5iPwBIBhGCfspUXgAQDAbASeALA1O9RkNyTRpQUAQEdA4AkA17YSFosUG0HgAQDAbASeAHAPWI4IU0iIxeRqAAAAgScA6liDBwCADoXAEwC1tpZ9tBi/AwBAh0DgCYDaBmZoAQDQkRB4AuB4lxarLAMA0BEQeALAvQYPXVoAAHQIBJ4AYJVlAAA6FgJPANSyjxYAAB0KgScAmJYOAEDHQuAJgOOztBi0DABAR0DgCQAGLQMA0LEQeAKALi0AADoWAk8A1DBLCwCADoXAEwB1zNICAKBDIfAEgHsMDy08AAB0CAQePzMMg1laAAB0MAQeP2tocsjuMCTRpQUAQEdB4PGzWptzwHKIRYqJCDW5GgAAIBF4/M7VnRUXGSaLxWJyNQAAQCLw+F0d43cAAOhwCDx+xpR0AAA6HgKPn9Wy6CAAAB0OgcfPatlWAgCADofA42c1LYEngTE8AAB0GAQeP6s5RpcWAAAdDYHHz1xdWgnRtPAAANBREHj8zLVTOl1aAAB0HAQeP3N1aSVE06UFAEBHQeDxsxr3tHRaeAAA6CgIPH5Wc8w1S4sWHgAAOgoCj5+5Ng9l0DIAAB0HgcfPjrfwEHgAAOgoCDx+5HAY7q0l6NICAKDjIPD4UX1jsxyG83u6tAAA6DgIPH7k2lYiIjREkWHcWgAAOgp+K/tRlbVRkrN1x2KxmFwNAABwIfD4UWWdM/CkxkWYXAkAADgRgcePKupskqTUuEiTKwEAACci8PiRq4UnhRYeAAA6FNMDz9KlS5WTk6OoqCjl5+dr/fr1p3z/2rVrlZ+fr6ioKOXm5uq5555rp0p/GC08AAB0TKYGnlWrVmn69OmaM2eOtm7dqpEjR2rs2LEqKSlp9f1FRUW6+uqrNXLkSG3dulWzZ8/WPffcozfeeKOdK29dea0z8NDCAwBAx2Jq4Fm8eLGmTJmiO+64QwMGDNCSJUvUq1cvLVu2rNX3P/fcc+rdu7eWLFmiAQMG6I477tDkyZP1X//1X+1ceet2l9dJknJTY02uBAAAnMi05YAbGxu1ZcsWPfTQQx7Hx4wZo40bN7Z6zqeffqoxY8Z4HLvqqqu0fPlyNTU1KTzce7E/m80mm83mfl5dXS1JqqmpOdMfwcOew3XaUVQqhyH1iPX/9QEA6Mpcv1cNwzit800LPBUVFbLb7crIyPA4npGRobKyslbPKSsra/X9zc3NqqioUPfu3b3OWbhwoebPn+91vFevXmdQ/akNXhKwSwMA0KXV1tYqMTHR5/NM3/Dp+wv0GYZxykX7Wnt/a8ddZs2apZkzZ7qfOxwOHTlyRCkpKX5fHLCmpka9evXS/v37lZCQ4Ndr4+S47+bgvpuD+24O7rs5Trzv8fHxqq2tVVZW1mldy7TAk5qaqtDQUK/WnPLycq9WHJfMzMxW3x8WFqaUlJRWz4mMjFRkpOesqaSkpNMvvA0SEhL4D8IE3HdzcN/NwX0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" + ] + }, + "metadata": {}, + "output_type": "display_data" + } + ], + "source": [ + "plt.plot(tspan_hr, yfull['RO'], label='Occupancy')\n", + "plt.ylabel(\"Receptor Occupancy\")\n", + "plt.xlabel(\"Time (hr.)\")\n", + "plt.ylim((0,1))\n", + "#plt.legend(loc='upper left')\n", + "plt.show()" + ] + } + ], + "metadata": { + "kernelspec": { + "display_name": "Python 3 (ipykernel)", + "language": "python", + "name": "python3" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.11.3" + } + }, + "nbformat": 4, + "nbformat_minor": 5 +} diff --git a/example-notebooks/1_simple-PKRO_schematic.png b/example-notebooks/1_simple-PKRO_schematic.png new file mode 100644 index 0000000000000000000000000000000000000000..e56b5767e7e779c07859b86451cdd765fe8c0db5 GIT binary patch literal 50300 zcmZsDcQ~8j_jiaDdlaqNnzcu2)oRtAEv>y(XzfukifGfKR*fR1bkJ69v16oK6hTYv zgs4?3s1g<9eSE*a-+R4(ynp0!dE`0g+-KeAKKJKHzG-R1!pO%60)bdejPJiHKYU>|N11Ph0IgnEPEaJc-vK)*0A zk6>^4pirLzk`^BbbP;5tfBkl3;RXR-=vNg%7cE{IE4)dxMEq^+%iX0cL`i5);c!EN%R_`$|2o{N zV+TpNS24r>67XRyvet?c+^7VK+wdgXyGOVA=_snj=`#7!wWVYX)4fE@;A2ho6t3&* z>r3Abn5Hrw_JlpaURQa_^4kXe_Ysc|=}2GaVgt3EM6DMG2S=H+X<#Y32XrICu`_`` zUAX=mIBZ$dLXMRcy8ILgzmA5&uOGx&z8l3eR#qy8xypcc3trbsY3X2o{38zVR2`C? z5!$yxWkf_oUX?7`UiG8K#=VPC*uU0E2WCcGKW=T@r5zk{D=zFUG@R?kMPp*T@#Gd!(YbaS!ms-E z*7V)f3oVKvv!b<+lai8*4Xi_DUWF)PPc%$9P4DI1VzK}BifsD#8t|TVNDkig7S3N$ zG2&(?Uxa;=&JQmZLHjRsUe8RPO|Wf6QoKx z1=-!E^1Q)Py48R+Yme6R_X>HdZZzLC|F zYHg+nSYlN`yvh1Gs*)+y+3$&?VTJuH?PjA}Q_<`LI>jMeR=|&oX9~FvC}dF)0dBgy z^-=B`pt$vhbt*d0OpZ3_jK_Ze7gNhDzB=amWb1=X&- z{R4kZ#St!Q_RWq{vt=}AgtgCfQBu(!5atjPTy0*twFYa9xSw#Q=Zx2jwxP;sNB2`# zm6{a^7Qw*cl8P#bv;{k$j7I=Nodv|wnfrL>nUVwE=Ke=_vf@oy!=FKv(kq#=GZN)v z-kci&gZ?+Ccg`r1OBZc)pIxcDi@VGB2O!=3NFMf-tB8teQyxYasxt zcSyzP()%;x_lA51Q#JiQ%^ltKlCCvJjrFT36bxkq=0mRxYFcNc$k)`Ja)-GfM7~>nR zQLVYpdray?G{dRWlCu+i2B$2p_~FZk~l317L>ButtGk z(VDQ++2u}34`{|Od!z{xv;RsW9dn;YMLR4I_&A ze+smOxy3~ht$)67XNSjShs_FxH7}lM)HhNGs|A-};#(JE&P2Qa28hK$-2Rp3A&>9B zRo0q+a>|8;b9}CuUp4Us{@m_uum{AFu^CV>%12eFHRYO$%5l59I*f_9I3@)dMHu zj>0=nexCbbKL1$3>0tH_G;*y{f_YibOpUXY<+j696WCs3|gH4z#zRw$8$O8rjH!O-Ml$H&fcKc%1{3 z)DPr1P7l~S2;tn*Zj8=F*<#Ag=v&Ev50wG|oveiRMyw;IeE&HEww3~mHvwdUJkr`x zkpoyV$yn{(qAj2Sed(uJPQW)f%Fdex0@*;n#Pjl5YT?LycB>!)Wc?4f!R*ek9R%-` z+KfE=b10B2<8xUsc zxk;ePe-d*tkSLdcAO-AOU+*po%Uq=J5Gsyvho<8kA6df)DEWRU^fyYuzXVmV~ zp2dj;vKp1I6!6^;O z{j#6)Od^5Pr;NH3RXTw{d# zDWW-Gjkze5#pxb`FzpGo01W0QA(#yq>1>}Hc_wY9h~~y^xDsQDA;bV8%SE4&yRby6 zVvquL2DR|ZDKM7*N)fG?nhErRDNqGbWq_(d**O1U%eGmI zgh2#9J~ldG(^eHdlfahHi)b3$aE0Od%(CFNl|rgvstbCNWSl~&5#0<(2bR{1v(h7-^blcUc_#|d3(dMY@|As{n^ zd!46iU6*C@!X#5O;(2{_wiiVbBFq;tu#*ocaq7h(+dJc!?i}%l8PC;Ut&u)>6XF}r zwsRcb1E|2Fuvgp%Dt`Q+3~q=Lm5E}+pOL4Rurj1L^YOSXHS})69W)7ZKA+jYpka7r za3jiHB$)crJn0)N*2lnHM3Y;6l;E_m-pYQUP}7NGfs;*OsyWY(Iv6(=NftXT@Pa94 z;$1zF=o=g%4=(3M__G~N5#nF$eSZau;Q8Kk9EK+hZpZ^Un*SHcEl1=m-&c)%0~DEG zhkT4^!3I5>oP%K*7dtlM@8E|IB6%Vo!7B569iA|S z{3&i=dqK(B3T27!M(4@gkp=j=l-ALhIDW1}PP)9N%O~_5%YEBDpst&pAjO%;%BerP z=|xd-rw-0VZ7z^b>DGQN=Yg75rnZhm79J}ePIC(dtuF+;nOM69Ej`sevLF^CLlY|z z?|w~)L1#V_=7x6)aqD{m8NgPM^WrSa0gUX?|1Q;dW>P3(v#frn*UWS5sC4ebQza3S zzf>PHaG~WT%vEPNzc~j6MUd&ArHU30L$b$OMWCLVQnPU*q!a%Es#ssLW7xNcuYcQ^ zgGeOo+%LQLtmJcggF8~l!{7V4$xX$)Va$Lr#ehtgWoz!xwT?A~H5$8=qsGAC=>Uq@ z8;h}tUyF7AF;w7$`0f?*{W(4y;RA-^jpT7g@%>nVWcRTK*i}6j9I*TIb#_(~8*LC+ z&>jzF1@S>%aa{}#3hpXt-e>Kbe*fJ3SBLS3#|M~WQw$~do?9G|B+PO3*0mG1i>L{T zNl`D5x&M=CEAs;(dA&1!IRAL)3>L>KUf;=wYJYjt{AnO{NgF6i)kQo{v27RhcQ#TM8Mi0E^x9=_2r&n*H0w-Mx^6tOsmWrQ`F(9gtv z!5J1z-Gt7ZYv!KhYn~)@riQdr9dS?oz{Lf@%JZi#LNyqrf7r z9cc?#9uP=B184RS6Sxh1rWD_wsHuLe!omW%VJ^zNpG@OA^i@toB

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