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32.77 181.39 l 32.01 181.62 l 31.25 181.87 l 30.49 182.13 l 29.73 182.41 l 28.97 182.72 l 28.21 183.04 l 27.45 183.40 l 26.69 183.79 l 25.93 184.21 l 25.17 184.70 l 24.41 185.25 l 23.65 185.92 l 22.89 186.81 l 22.13 189.00 l h f 22.13 189.00 m 22.89 191.18 l 23.65 192.07 l 24.41 192.74 l 25.17 193.30 l 25.93 193.78 l 26.69 194.21 l 27.45 194.60 l 28.21 194.95 l 28.97 195.28 l 29.73 195.58 l 30.49 195.86 l 31.25 196.13 l 32.01 196.38 l 32.77 196.61 l 33.53 196.83 l 34.29 197.04 l 35.05 197.24 l 35.81 197.42 l 36.57 197.60 l 37.33 197.77 l 38.09 197.93 l 38.85 198.08 l 39.61 198.22 l 40.37 198.36 l 41.13 198.49 l 41.89 198.61 l 42.65 198.73 l 43.41 198.84 l 44.17 198.94 l 44.93 199.04 l 45.69 199.13 l 46.45 199.21 l 47.21 199.30 l 47.97 199.37 l 48.73 199.44 l 49.49 199.51 l 50.25 199.57 l 51.01 199.62 l 51.77 199.67 l 52.53 199.72 l 53.29 199.76 l 54.05 199.79 l 54.81 199.83 l 55.57 199.85 l 56.33 199.87 l 57.09 199.89 l 57.85 199.91 l 58.61 199.91 l 59.37 199.92 l 60.13 199.92 l 60.89 199.91 l 61.65 199.91 l 62.41 199.89 l 63.17 199.87 l 63.93 199.85 l 64.69 199.83 l 65.45 199.79 l 66.21 199.76 l 66.97 199.72 l 67.73 199.67 l 68.49 199.62 l 69.25 199.57 l 70.01 199.51 l 70.77 199.44 l 71.53 199.37 l 72.29 199.30 l 73.05 199.21 l 73.81 199.13 l 74.57 199.04 l 75.33 198.94 l 76.09 198.84 l 76.85 198.73 l 77.61 198.61 l 78.37 198.49 l 79.13 198.36 l 79.89 198.22 l 80.65 198.08 l 81.41 197.93 l 82.17 197.77 l 82.93 197.60 l 83.69 197.42 l 84.45 197.24 l 85.21 197.04 l 85.97 196.83 l 86.73 196.61 l 87.49 196.38 l 88.25 196.13 l 89.01 195.86 l 89.77 195.58 l 90.53 195.28 l 91.29 194.95 l 92.05 194.60 l 92.81 194.21 l 93.57 193.78 l 94.33 193.30 l 95.09 192.74 l 95.85 192.07 l 96.61 191.18 l 97.37 189.00 l 97.37 189.00 l 96.61 186.81 l 95.85 185.92 l 95.09 185.25 l 94.33 184.70 l 93.57 184.21 l 92.81 183.79 l 92.05 183.40 l 91.29 183.04 l 90.53 182.72 l 89.77 182.41 l 89.01 182.13 l 88.25 181.87 l 87.49 181.62 l 86.73 181.39 l 85.97 181.17 l 85.21 180.96 l 84.45 180.76 l 83.69 180.57 l 82.93 180.39 l 82.17 180.23 l 81.41 180.07 l 80.65 179.92 l 79.89 179.77 l 79.13 179.64 l 78.37 179.51 l 77.61 179.38 l 76.85 179.27 l 76.09 179.16 l 75.33 179.06 l 74.57 178.96 l 73.81 178.87 l 73.05 178.78 l 72.29 178.70 l 71.53 178.62 l 70.77 178.55 l 70.01 178.49 l 69.25 178.43 l 68.49 178.37 l 67.73 178.32 l 66.97 178.28 l 66.21 178.24 l 65.45 178.20 l 64.69 178.17 l 63.93 178.14 l 63.17 178.12 l 62.41 178.10 l 61.65 178.09 l 60.89 178.08 l 60.13 178.08 l 59.37 178.08 l 58.61 178.08 l 57.85 178.09 l 57.09 178.10 l 56.33 178.12 l 55.57 178.14 l 54.81 178.17 l 54.05 178.20 l 53.29 178.24 l 52.53 178.28 l 51.77 178.32 l 51.01 178.37 l 50.25 178.43 l 49.49 178.49 l 48.73 178.55 l 47.97 178.62 l 47.21 178.70 l 46.45 178.78 l 45.69 178.87 l 44.93 178.96 l 44.17 179.06 l 43.41 179.16 l 42.65 179.27 l 41.89 179.38 l 41.13 179.51 l 40.37 179.64 l 39.61 179.77 l 38.85 179.92 l 38.09 180.07 l 37.33 180.23 l 36.57 180.39 l 35.81 180.57 l 35.05 180.76 l 34.29 180.96 l 33.53 181.17 l 32.77 181.39 l 32.01 181.62 l 31.25 181.87 l 30.49 182.13 l 29.73 182.41 l 28.97 182.72 l 28.21 183.04 l 27.45 183.40 l 26.69 183.79 l 25.93 184.21 l 25.17 184.70 l 24.41 185.25 l 23.65 185.92 l 22.89 186.81 l 22.13 189.00 l 22.13 189.00 l S BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 35.22 186.70 Tm [(tr) 10 (anscr) -15 (iption)] TJ ET 315.82 125.28 48.54 21.84 re S BT /F2 1 Tf 9.00 0.00 -0.00 9.00 319.21 132.97 Tm (RB/E2F-1) Tj ET 85.23 125.28 106.80 21.84 re S BT /F2 1 Tf 9.00 0.00 -0.00 9.00 88.13 132.97 Tm (CDK4/CYCLIN D1/PCNA) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 299.86 26.18 Tm (RB) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 248.43 26.18 Tm (E2F-1) Tj ET 1.000 0.000 0.000 rg 178.68 71.89 55.83 21.84 re B BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 182.59 79.60 Tm (modification) Tj ET 202.95 125.28 101.94 21.84 re S BT /F2 1 Tf 9.00 0.00 -0.00 9.00 206.17 132.97 Tm (CDK2/CYCLIN E/PCNA) Tj ET 1.000 0.000 0.000 rg 245.43 71.89 55.83 21.84 re B BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 249.33 79.60 Tm (modification) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 380.30 133.13 Tm (100127) Tj ET 1.000 0.000 0.000 rg 312.18 71.89 55.83 21.84 re B BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 316.08 79.60 Tm (modification) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 129.08 345.51 Tm (101176) Tj ET 1.000 1.000 0.000 rg 105.26 401.98 m 106.02 404.17 l 106.78 405.06 l 107.54 405.73 l 108.30 406.29 l 109.06 406.77 l 109.82 407.20 l 110.58 407.58 l 111.34 407.94 l 112.10 408.26 l 112.86 408.57 l 113.62 408.85 l 114.38 409.11 l 115.14 409.36 l 115.90 409.60 l 116.66 409.82 l 117.42 410.02 l 118.18 410.22 l 118.94 410.41 l 119.70 410.59 l 120.46 410.75 l 121.22 410.91 l 121.98 411.07 l 122.74 411.21 l 123.50 411.35 l 124.26 411.47 l 125.02 411.60 l 125.78 411.71 l 126.54 411.82 l 127.30 411.93 l 128.06 412.02 l 128.82 412.11 l 129.58 412.20 l 130.34 412.28 l 131.10 412.36 l 131.86 412.43 l 132.62 412.49 l 133.38 412.55 l 134.14 412.61 l 134.90 412.66 l 135.66 412.70 l 136.42 412.74 l 137.18 412.78 l 137.94 412.81 l 138.70 412.84 l 139.46 412.86 l 140.22 412.88 l 140.98 412.89 l 141.74 412.90 l 142.50 412.91 l 143.26 412.91 l 144.02 412.90 l 144.78 412.89 l 145.54 412.88 l 146.30 412.86 l 147.06 412.84 l 147.82 412.81 l 148.58 412.78 l 149.34 412.74 l 150.10 412.70 l 150.86 412.66 l 151.62 412.61 l 152.38 412.55 l 153.14 412.49 l 153.90 412.43 l 154.66 412.36 l 155.42 412.28 l 156.18 412.20 l 156.94 412.11 l 157.70 412.02 l 158.46 411.93 l 159.22 411.82 l 159.98 411.71 l 160.74 411.60 l 161.50 411.47 l 162.26 411.35 l 163.02 411.21 l 163.78 411.07 l 164.54 410.91 l 165.30 410.75 l 166.06 410.59 l 166.82 410.41 l 167.58 410.22 l 168.34 410.02 l 169.10 409.82 l 169.86 409.60 l 170.62 409.36 l 171.38 409.11 l 172.14 408.85 l 172.90 408.57 l 173.66 408.26 l 174.42 407.94 l 175.18 407.58 l 175.94 407.20 l 176.70 406.77 l 177.46 406.29 l 178.22 405.73 l 178.98 405.06 l 179.74 404.17 l 180.50 401.98 l 180.50 401.98 l 179.74 399.80 l 178.98 398.91 l 178.22 398.24 l 177.46 397.68 l 176.70 397.20 l 175.94 396.77 l 175.18 396.38 l 174.42 396.03 l 173.66 395.70 l 172.90 395.40 l 172.14 395.12 l 171.38 394.85 l 170.62 394.61 l 169.86 394.37 l 169.10 394.15 l 168.34 393.94 l 167.58 393.75 l 166.82 393.56 l 166.06 393.38 l 165.30 393.21 l 164.54 393.05 l 163.78 392.90 l 163.02 392.76 l 162.26 392.62 l 161.50 392.49 l 160.74 392.37 l 159.98 392.25 l 159.22 392.15 l 158.46 392.04 l 157.70 391.94 l 156.94 391.85 l 156.18 391.77 l 155.42 391.69 l 154.66 391.61 l 153.90 391.54 l 153.14 391.48 l 152.38 391.42 l 151.62 391.36 l 150.86 391.31 l 150.10 391.26 l 149.34 391.22 l 148.58 391.19 l 147.82 391.16 l 147.06 391.13 l 146.30 391.11 l 145.54 391.09 l 144.78 391.08 l 144.02 391.07 l 143.26 391.06 l 142.50 391.06 l 141.74 391.07 l 140.98 391.08 l 140.22 391.09 l 139.46 391.11 l 138.70 391.13 l 137.94 391.16 l 137.18 391.19 l 136.42 391.22 l 135.66 391.26 l 134.90 391.31 l 134.14 391.36 l 133.38 391.42 l 132.62 391.48 l 131.86 391.54 l 131.10 391.61 l 130.34 391.69 l 129.58 391.77 l 128.82 391.85 l 128.06 391.94 l 127.30 392.04 l 126.54 392.15 l 125.78 392.25 l 125.02 392.37 l 124.26 392.49 l 123.50 392.62 l 122.74 392.76 l 121.98 392.90 l 121.22 393.05 l 120.46 393.21 l 119.70 393.38 l 118.94 393.56 l 118.18 393.75 l 117.42 393.94 l 116.66 394.15 l 115.90 394.37 l 115.14 394.61 l 114.38 394.85 l 113.62 395.12 l 112.86 395.40 l 112.10 395.70 l 111.34 396.03 l 110.58 396.38 l 109.82 396.77 l 109.06 397.20 l 108.30 397.68 l 107.54 398.24 l 106.78 398.91 l 106.02 399.80 l 105.26 401.98 l h f 105.26 401.98 m 106.02 404.17 l 106.78 405.06 l 107.54 405.73 l 108.30 406.29 l 109.06 406.77 l 109.82 407.20 l 110.58 407.58 l 111.34 407.94 l 112.10 408.26 l 112.86 408.57 l 113.62 408.85 l 114.38 409.11 l 115.14 409.36 l 115.90 409.60 l 116.66 409.82 l 117.42 410.02 l 118.18 410.22 l 118.94 410.41 l 119.70 410.59 l 120.46 410.75 l 121.22 410.91 l 121.98 411.07 l 122.74 411.21 l 123.50 411.35 l 124.26 411.47 l 125.02 411.60 l 125.78 411.71 l 126.54 411.82 l 127.30 411.93 l 128.06 412.02 l 128.82 412.11 l 129.58 412.20 l 130.34 412.28 l 131.10 412.36 l 131.86 412.43 l 132.62 412.49 l 133.38 412.55 l 134.14 412.61 l 134.90 412.66 l 135.66 412.70 l 136.42 412.74 l 137.18 412.78 l 137.94 412.81 l 138.70 412.84 l 139.46 412.86 l 140.22 412.88 l 140.98 412.89 l 141.74 412.90 l 142.50 412.91 l 143.26 412.91 l 144.02 412.90 l 144.78 412.89 l 145.54 412.88 l 146.30 412.86 l 147.06 412.84 l 147.82 412.81 l 148.58 412.78 l 149.34 412.74 l 150.10 412.70 l 150.86 412.66 l 151.62 412.61 l 152.38 412.55 l 153.14 412.49 l 153.90 412.43 l 154.66 412.36 l 155.42 412.28 l 156.18 412.20 l 156.94 412.11 l 157.70 412.02 l 158.46 411.93 l 159.22 411.82 l 159.98 411.71 l 160.74 411.60 l 161.50 411.47 l 162.26 411.35 l 163.02 411.21 l 163.78 411.07 l 164.54 410.91 l 165.30 410.75 l 166.06 410.59 l 166.82 410.41 l 167.58 410.22 l 168.34 410.02 l 169.10 409.82 l 169.86 409.60 l 170.62 409.36 l 171.38 409.11 l 172.14 408.85 l 172.90 408.57 l 173.66 408.26 l 174.42 407.94 l 175.18 407.58 l 175.94 407.20 l 176.70 406.77 l 177.46 406.29 l 178.22 405.73 l 178.98 405.06 l 179.74 404.17 l 180.50 401.98 l 180.50 401.98 l 179.74 399.80 l 178.98 398.91 l 178.22 398.24 l 177.46 397.68 l 176.70 397.20 l 175.94 396.77 l 175.18 396.38 l 174.42 396.03 l 173.66 395.70 l 172.90 395.40 l 172.14 395.12 l 171.38 394.85 l 170.62 394.61 l 169.86 394.37 l 169.10 394.15 l 168.34 393.94 l 167.58 393.75 l 166.82 393.56 l 166.06 393.38 l 165.30 393.21 l 164.54 393.05 l 163.78 392.90 l 163.02 392.76 l 162.26 392.62 l 161.50 392.49 l 160.74 392.37 l 159.98 392.25 l 159.22 392.15 l 158.46 392.04 l 157.70 391.94 l 156.94 391.85 l 156.18 391.77 l 155.42 391.69 l 154.66 391.61 l 153.90 391.54 l 153.14 391.48 l 152.38 391.42 l 151.62 391.36 l 150.86 391.31 l 150.10 391.26 l 149.34 391.22 l 148.58 391.19 l 147.82 391.16 l 147.06 391.13 l 146.30 391.11 l 145.54 391.09 l 144.78 391.08 l 144.02 391.07 l 143.26 391.06 l 142.50 391.06 l 141.74 391.07 l 140.98 391.08 l 140.22 391.09 l 139.46 391.11 l 138.70 391.13 l 137.94 391.16 l 137.18 391.19 l 136.42 391.22 l 135.66 391.26 l 134.90 391.31 l 134.14 391.36 l 133.38 391.42 l 132.62 391.48 l 131.86 391.54 l 131.10 391.61 l 130.34 391.69 l 129.58 391.77 l 128.82 391.85 l 128.06 391.94 l 127.30 392.04 l 126.54 392.15 l 125.78 392.25 l 125.02 392.37 l 124.26 392.49 l 123.50 392.62 l 122.74 392.76 l 121.98 392.90 l 121.22 393.05 l 120.46 393.21 l 119.70 393.38 l 118.94 393.56 l 118.18 393.75 l 117.42 393.94 l 116.66 394.15 l 115.90 394.37 l 115.14 394.61 l 114.38 394.85 l 113.62 395.12 l 112.86 395.40 l 112.10 395.70 l 111.34 396.03 l 110.58 396.38 l 109.82 396.77 l 109.06 397.20 l 108.30 397.68 l 107.54 398.24 l 106.78 398.91 l 106.02 399.80 l 105.26 401.98 l 105.26 401.98 l S BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 118.35 399.68 Tm [(tr) 10 (anscr) -15 (iption)] TJ ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 177.63 239.32 Tm (101473) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 227.39 239.16 Tm (CYCLIN D1) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 75.68 239.32 Tm (100515) Tj ET 1.000 0.000 0.000 rg 113.75 178.08 55.83 21.84 re B BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 117.66 185.79 Tm (modification) Tj ET 0.000 1.000 0.000 RG 102.83 337.66 m 104.12 335.39 l 105.44 332.97 l 106.79 330.42 l 108.14 327.78 l 109.51 325.07 l 110.87 322.33 l 112.23 319.58 l 113.57 316.85 l 114.89 314.17 l 116.18 311.57 l S 114.89 314.17 m 116.18 311.57 l S 110.39 315.42 m 116.18 311.57 l 116.62 318.51 l S 93.12 337.66 m 92.01 335.01 l 90.88 332.17 l 89.72 329.17 l 88.54 326.03 l 87.36 322.80 l 86.18 319.49 l 85.00 316.14 l 83.84 312.77 l 82.70 309.42 l 81.59 306.11 l S 81.59 306.11 m 79.19 299.52 l 77.04 293.80 l 75.11 288.74 l 73.38 284.12 l 71.81 279.71 l 70.37 275.31 l 69.02 270.68 l 67.73 265.62 l 66.47 259.91 l 65.21 253.32 l S 65.21 253.32 m 64.19 248.52 l 63.30 243.62 l 62.54 238.66 l 61.89 233.69 l 61.34 228.74 l 60.89 223.87 l 60.51 219.12 l 60.20 214.52 l 59.95 210.13 l 59.75 205.99 l S 59.95 210.13 m 59.75 205.99 l S 56.57 212.17 m 59.75 205.99 l 63.52 211.83 l S 141.67 231.47 m 141.67 229.22 l 141.67 226.84 l 141.67 224.36 l 141.67 221.80 l 141.67 219.19 l 141.67 216.53 l 141.67 213.86 l 141.67 211.20 l 141.67 208.57 l 141.67 205.99 l S 141.67 208.57 m 141.67 205.99 l S 138.19 212.01 m 141.67 205.99 l 145.14 212.01 l S 0.000 0.000 0.000 RG 128.32 284.26 m 129.06 282.01 l 129.84 279.64 l 130.63 277.17 l 131.44 274.63 l 132.26 272.05 l 133.08 269.45 l 133.89 266.86 l 134.69 264.30 l 135.46 261.80 l 136.21 259.39 l S 135.46 261.80 m 136.21 259.39 l S 131.11 264.12 m 136.21 259.39 l 137.75 266.16 l S 1.000 0.000 0.000 RG 62.78 391.06 m 64.67 388.63 l 66.69 386.07 l 68.80 383.42 l 71.00 380.70 l 73.25 377.94 l 75.54 375.16 l 77.85 372.38 l 80.14 369.64 l 82.41 366.96 l 84.63 364.36 l S 82.41 366.96 m 84.63 364.36 l S 78.07 366.69 m 84.63 364.36 l 83.36 371.20 l S 0.000 0.000 0.000 RG 54.29 391.06 m 54.12 388.81 l 53.99 386.43 l 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