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177.82 l 52.89 177.87 l 52.11 177.93 l 51.32 178.00 l 50.54 178.07 l 49.76 178.14 l 48.97 178.22 l 48.19 178.31 l 47.41 178.40 l 46.62 178.50 l 45.84 178.60 l 45.06 178.71 l 44.27 178.83 l 43.49 178.95 l 42.71 179.08 l 41.92 179.22 l 41.14 179.36 l 40.36 179.51 l 39.58 179.68 l 38.79 179.85 l 38.01 180.02 l 37.23 180.21 l 36.44 180.41 l 35.66 180.62 l 34.88 180.85 l 34.09 181.08 l 33.31 181.33 l 32.53 181.59 l 31.74 181.88 l 30.96 182.18 l 30.18 182.50 l 29.39 182.85 l 28.61 183.22 l 27.83 183.64 l 27.04 184.09 l 26.26 184.61 l 25.48 185.20 l 24.69 185.91 l 23.91 186.86 l 23.13 189.19 l h f 23.13 189.19 m 23.91 191.51 l 24.69 192.46 l 25.48 193.17 l 26.26 193.77 l 27.04 194.28 l 27.83 194.74 l 28.61 195.15 l 29.39 195.52 l 30.18 195.87 l 30.96 196.19 l 31.74 196.50 l 32.53 196.78 l 33.31 197.04 l 34.09 197.29 l 34.88 197.53 l 35.66 197.75 l 36.44 197.96 l 37.23 198.16 l 38.01 198.35 l 38.79 198.52 l 39.58 198.69 l 40.36 198.86 l 41.14 199.01 l 41.92 199.15 l 42.71 199.29 l 43.49 199.42 l 44.27 199.54 l 45.06 199.66 l 45.84 199.77 l 46.62 199.88 l 47.41 199.97 l 48.19 200.06 l 48.97 200.15 l 49.76 200.23 l 50.54 200.31 l 51.32 200.37 l 52.11 200.44 l 52.89 200.50 l 53.67 200.55 l 54.46 200.60 l 55.24 200.64 l 56.02 200.68 l 56.81 200.72 l 57.59 200.74 l 58.37 200.77 l 59.16 200.79 l 59.94 200.80 l 60.72 200.81 l 61.50 200.82 l 62.29 200.82 l 63.07 200.81 l 63.85 200.80 l 64.64 200.79 l 65.42 200.77 l 66.20 200.74 l 66.99 200.72 l 67.77 200.68 l 68.55 200.64 l 69.34 200.60 l 70.12 200.55 l 70.90 200.50 l 71.69 200.44 l 72.47 200.37 l 73.25 200.31 l 74.04 200.23 l 74.82 200.15 l 75.60 200.06 l 76.39 199.97 l 77.17 199.88 l 77.95 199.77 l 78.73 199.66 l 79.52 199.54 l 80.30 199.42 l 81.08 199.29 l 81.87 199.15 l 82.65 199.01 l 83.43 198.86 l 84.22 198.69 l 85.00 198.52 l 85.78 198.35 l 86.57 198.16 l 87.35 197.96 l 88.13 197.75 l 88.92 197.53 l 89.70 197.29 l 90.48 197.04 l 91.27 196.78 l 92.05 196.50 l 92.83 196.19 l 93.62 195.87 l 94.40 195.52 l 95.18 195.15 l 95.97 194.74 l 96.75 194.28 l 97.53 193.77 l 98.31 193.17 l 99.10 192.46 l 99.88 191.51 l 100.66 189.19 l 100.66 189.19 l 99.88 186.86 l 99.10 185.91 l 98.31 185.20 l 97.53 184.61 l 96.75 184.09 l 95.97 183.64 l 95.18 183.22 l 94.40 182.85 l 93.62 182.50 l 92.83 182.18 l 92.05 181.88 l 91.27 181.59 l 90.48 181.33 l 89.70 181.08 l 88.92 180.85 l 88.13 180.62 l 87.35 180.41 l 86.57 180.21 l 85.78 180.02 l 85.00 179.85 l 84.22 179.68 l 83.43 179.51 l 82.65 179.36 l 81.87 179.22 l 81.08 179.08 l 80.30 178.95 l 79.52 178.83 l 78.73 178.71 l 77.95 178.60 l 77.17 178.50 l 76.39 178.40 l 75.60 178.31 l 74.82 178.22 l 74.04 178.14 l 73.25 178.07 l 72.47 178.00 l 71.69 177.93 l 70.90 177.87 l 70.12 177.82 l 69.34 177.77 l 68.55 177.73 l 67.77 177.69 l 66.99 177.66 l 66.20 177.63 l 65.42 177.60 l 64.64 177.58 l 63.85 177.57 l 63.07 177.56 l 62.29 177.56 l 61.50 177.56 l 60.72 177.56 l 59.94 177.57 l 59.16 177.58 l 58.37 177.60 l 57.59 177.63 l 56.81 177.66 l 56.02 177.69 l 55.24 177.73 l 54.46 177.77 l 53.67 177.82 l 52.89 177.87 l 52.11 177.93 l 51.32 178.00 l 50.54 178.07 l 49.76 178.14 l 48.97 178.22 l 48.19 178.31 l 47.41 178.40 l 46.62 178.50 l 45.84 178.60 l 45.06 178.71 l 44.27 178.83 l 43.49 178.95 l 42.71 179.08 l 41.92 179.22 l 41.14 179.36 l 40.36 179.51 l 39.58 179.68 l 38.79 179.85 l 38.01 180.02 l 37.23 180.21 l 36.44 180.41 l 35.66 180.62 l 34.88 180.85 l 34.09 181.08 l 33.31 181.33 l 32.53 181.59 l 31.74 181.88 l 30.96 182.18 l 30.18 182.50 l 29.39 182.85 l 28.61 183.22 l 27.83 183.64 l 27.04 184.09 l 26.26 184.61 l 25.48 185.20 l 24.69 185.91 l 23.91 186.86 l 23.13 189.19 l 23.13 189.19 l S BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 37.37 186.89 Tm [(tr) 10 (anscr) -15 (iption)] TJ ET 321.00 124.57 46.52 23.26 re S BT /F2 1 Tf 9.00 0.00 -0.00 9.00 323.37 132.97 Tm (RB/E2F-1) Tj ET 85.80 124.57 108.55 23.26 re S BT /F2 1 Tf 9.00 0.00 -0.00 9.00 89.57 132.97 Tm (CDK4/CYCLIN D1/PCNA) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 306.99 26.36 Tm (RB) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 253.34 26.36 Tm (E2F-1) Tj ET 1.000 0.000 0.000 rg 182.08 70.94 55.57 23.26 re B BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 185.85 79.36 Tm (modification) Tj ET 205.98 124.57 103.38 23.26 re S BT /F2 1 Tf 9.00 0.00 -0.00 9.00 209.92 132.97 Tm (CDK2/CYCLIN E/PCNA) Tj ET 1.000 0.000 0.000 rg 249.28 70.94 55.57 23.26 re B BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 253.05 79.36 Tm (modification) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 382.23 133.12 Tm (100127) Tj ET 1.000 0.000 0.000 rg 316.47 70.94 55.57 23.26 re B BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 320.25 79.36 Tm (modification) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 132.82 345.70 Tm (101176) Tj ET 1.000 1.000 0.000 rg 107.77 401.76 m 108.56 404.09 l 109.34 405.04 l 110.12 405.75 l 110.90 406.34 l 111.69 406.86 l 112.47 407.31 l 113.25 407.73 l 114.04 408.10 l 114.82 408.45 l 115.60 408.77 l 116.39 409.07 l 117.17 409.36 l 117.95 409.62 l 118.74 409.87 l 119.52 410.10 l 120.30 410.33 l 121.09 410.54 l 121.87 410.74 l 122.65 410.92 l 123.44 411.10 l 124.22 411.27 l 125.00 411.43 l 125.79 411.59 l 126.57 411.73 l 127.35 411.87 l 128.14 412.00 l 128.92 412.12 l 129.70 412.24 l 130.48 412.35 l 131.27 412.45 l 132.05 412.55 l 132.83 412.64 l 133.62 412.73 l 134.40 412.81 l 135.18 412.88 l 135.97 412.95 l 136.75 413.02 l 137.53 413.08 l 138.32 413.13 l 139.10 413.18 l 139.88 413.22 l 140.67 413.26 l 141.45 413.29 l 142.23 413.32 l 143.02 413.35 l 143.80 413.37 l 144.58 413.38 l 145.37 413.39 l 146.15 413.39 l 146.93 413.39 l 147.72 413.39 l 148.50 413.38 l 149.28 413.37 l 150.06 413.35 l 150.85 413.32 l 151.63 413.29 l 152.41 413.26 l 153.20 413.22 l 153.98 413.18 l 154.76 413.13 l 155.55 413.08 l 156.33 413.02 l 157.11 412.95 l 157.90 412.88 l 158.68 412.81 l 159.46 412.73 l 160.25 412.64 l 161.03 412.55 l 161.81 412.45 l 162.60 412.35 l 163.38 412.24 l 164.16 412.12 l 164.95 412.00 l 165.73 411.87 l 166.51 411.73 l 167.29 411.59 l 168.08 411.43 l 168.86 411.27 l 169.64 411.10 l 170.43 410.92 l 171.21 410.74 l 171.99 410.54 l 172.78 410.33 l 173.56 410.10 l 174.34 409.87 l 175.13 409.62 l 175.91 409.36 l 176.69 409.07 l 177.48 408.77 l 178.26 408.45 l 179.04 408.10 l 179.83 407.73 l 180.61 407.31 l 181.39 406.86 l 182.18 406.34 l 182.96 405.75 l 183.74 405.04 l 184.53 404.09 l 185.31 401.76 l 185.31 401.76 l 184.53 399.44 l 183.74 398.49 l 182.96 397.78 l 182.18 397.18 l 181.39 396.67 l 180.61 396.21 l 179.83 395.80 l 179.04 395.42 l 178.26 395.08 l 177.48 394.75 l 176.69 394.45 l 175.91 394.17 l 175.13 393.91 l 174.34 393.66 l 173.56 393.42 l 172.78 393.20 l 171.99 392.99 l 171.21 392.79 l 170.43 392.60 l 169.64 392.43 l 168.86 392.26 l 168.08 392.09 l 167.29 391.94 l 166.51 391.80 l 165.73 391.66 l 164.95 391.53 l 164.16 391.40 l 163.38 391.29 l 162.60 391.18 l 161.81 391.07 l 161.03 390.98 l 160.25 390.89 l 159.46 390.80 l 158.68 390.72 l 157.90 390.64 l 157.11 390.57 l 156.33 390.51 l 155.55 390.45 l 154.76 390.40 l 153.98 390.35 l 153.20 390.31 l 152.41 390.27 l 151.63 390.23 l 150.85 390.21 l 150.06 390.18 l 149.28 390.16 l 148.50 390.15 l 147.72 390.14 l 146.93 390.13 l 146.15 390.13 l 145.37 390.14 l 144.58 390.15 l 143.80 390.16 l 143.02 390.18 l 142.23 390.21 l 141.45 390.23 l 140.67 390.27 l 139.88 390.31 l 139.10 390.35 l 138.32 390.40 l 137.53 390.45 l 136.75 390.51 l 135.97 390.57 l 135.18 390.64 l 134.40 390.72 l 133.62 390.80 l 132.83 390.89 l 132.05 390.98 l 131.27 391.07 l 130.48 391.18 l 129.70 391.29 l 128.92 391.40 l 128.14 391.53 l 127.35 391.66 l 126.57 391.80 l 125.79 391.94 l 125.00 392.09 l 124.22 392.26 l 123.44 392.43 l 122.65 392.60 l 121.87 392.79 l 121.09 392.99 l 120.30 393.20 l 119.52 393.42 l 118.74 393.66 l 117.95 393.91 l 117.17 394.17 l 116.39 394.45 l 115.60 394.75 l 114.82 395.08 l 114.04 395.42 l 113.25 395.80 l 112.47 396.21 l 111.69 396.67 l 110.90 397.18 l 110.12 397.78 l 109.34 398.49 l 108.56 399.44 l 107.77 401.76 l h f 107.77 401.76 m 108.56 404.09 l 109.34 405.04 l 110.12 405.75 l 110.90 406.34 l 111.69 406.86 l 112.47 407.31 l 113.25 407.73 l 114.04 408.10 l 114.82 408.45 l 115.60 408.77 l 116.39 409.07 l 117.17 409.36 l 117.95 409.62 l 118.74 409.87 l 119.52 410.10 l 120.30 410.33 l 121.09 410.54 l 121.87 410.74 l 122.65 410.92 l 123.44 411.10 l 124.22 411.27 l 125.00 411.43 l 125.79 411.59 l 126.57 411.73 l 127.35 411.87 l 128.14 412.00 l 128.92 412.12 l 129.70 412.24 l 130.48 412.35 l 131.27 412.45 l 132.05 412.55 l 132.83 412.64 l 133.62 412.73 l 134.40 412.81 l 135.18 412.88 l 135.97 412.95 l 136.75 413.02 l 137.53 413.08 l 138.32 413.13 l 139.10 413.18 l 139.88 413.22 l 140.67 413.26 l 141.45 413.29 l 142.23 413.32 l 143.02 413.35 l 143.80 413.37 l 144.58 413.38 l 145.37 413.39 l 146.15 413.39 l 146.93 413.39 l 147.72 413.39 l 148.50 413.38 l 149.28 413.37 l 150.06 413.35 l 150.85 413.32 l 151.63 413.29 l 152.41 413.26 l 153.20 413.22 l 153.98 413.18 l 154.76 413.13 l 155.55 413.08 l 156.33 413.02 l 157.11 412.95 l 157.90 412.88 l 158.68 412.81 l 159.46 412.73 l 160.25 412.64 l 161.03 412.55 l 161.81 412.45 l 162.60 412.35 l 163.38 412.24 l 164.16 412.12 l 164.95 412.00 l 165.73 411.87 l 166.51 411.73 l 167.29 411.59 l 168.08 411.43 l 168.86 411.27 l 169.64 411.10 l 170.43 410.92 l 171.21 410.74 l 171.99 410.54 l 172.78 410.33 l 173.56 410.10 l 174.34 409.87 l 175.13 409.62 l 175.91 409.36 l 176.69 409.07 l 177.48 408.77 l 178.26 408.45 l 179.04 408.10 l 179.83 407.73 l 180.61 407.31 l 181.39 406.86 l 182.18 406.34 l 182.96 405.75 l 183.74 405.04 l 184.53 404.09 l 185.31 401.76 l 185.31 401.76 l 184.53 399.44 l 183.74 398.49 l 182.96 397.78 l 182.18 397.18 l 181.39 396.67 l 180.61 396.21 l 179.83 395.80 l 179.04 395.42 l 178.26 395.08 l 177.48 394.75 l 176.69 394.45 l 175.91 394.17 l 175.13 393.91 l 174.34 393.66 l 173.56 393.42 l 172.78 393.20 l 171.99 392.99 l 171.21 392.79 l 170.43 392.60 l 169.64 392.43 l 168.86 392.26 l 168.08 392.09 l 167.29 391.94 l 166.51 391.80 l 165.73 391.66 l 164.95 391.53 l 164.16 391.40 l 163.38 391.29 l 162.60 391.18 l 161.81 391.07 l 161.03 390.98 l 160.25 390.89 l 159.46 390.80 l 158.68 390.72 l 157.90 390.64 l 157.11 390.57 l 156.33 390.51 l 155.55 390.45 l 154.76 390.40 l 153.98 390.35 l 153.20 390.31 l 152.41 390.27 l 151.63 390.23 l 150.85 390.21 l 150.06 390.18 l 149.28 390.16 l 148.50 390.15 l 147.72 390.14 l 146.93 390.13 l 146.15 390.13 l 145.37 390.14 l 144.58 390.15 l 143.80 390.16 l 143.02 390.18 l 142.23 390.21 l 141.45 390.23 l 140.67 390.27 l 139.88 390.31 l 139.10 390.35 l 138.32 390.40 l 137.53 390.45 l 136.75 390.51 l 135.97 390.57 l 135.18 390.64 l 134.40 390.72 l 133.62 390.80 l 132.83 390.89 l 132.05 390.98 l 131.27 391.07 l 130.48 391.18 l 129.70 391.29 l 128.92 391.40 l 128.14 391.53 l 127.35 391.66 l 126.57 391.80 l 125.79 391.94 l 125.00 392.09 l 124.22 392.26 l 123.44 392.43 l 122.65 392.60 l 121.87 392.79 l 121.09 392.99 l 120.30 393.20 l 119.52 393.42 l 118.74 393.66 l 117.95 393.91 l 117.17 394.17 l 116.39 394.45 l 115.60 394.75 l 114.82 395.08 l 114.04 395.42 l 113.25 395.80 l 112.47 396.21 l 111.69 396.67 l 110.90 397.18 l 110.12 397.78 l 109.34 398.49 l 108.56 399.44 l 107.77 401.76 l 107.77 401.76 l S BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 122.01 399.46 Tm [(tr) 10 (anscr) -15 (iption)] TJ ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 175.47 239.09 Tm (101473) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 225.13 238.94 Tm (CYCLIN D1) Tj ET BT /F2 1 Tf 9.00 0.00 -0.00 9.00 79.84 239.09 Tm (100515) Tj ET 1.000 0.000 0.000 rg 114.88 177.55 55.57 23.26 re B BT 0.000 0.000 0.000 rg /F2 1 Tf 9.00 0.00 -0.00 9.00 118.66 185.98 Tm (modification) Tj ET 0.000 1.000 0.000 RG 107.13 337.15 m 108.31 334.96 l 109.52 332.67 l 110.77 330.30 l 112.05 327.86 l 113.34 325.36 l 114.66 322.82 l 116.00 320.26 l 117.34 317.69 l 118.69 315.13 l 120.05 312.60 l S 118.69 315.13 m 120.05 312.60 l S 113.76 316.51 m 120.05 312.60 l 120.29 320.00 l S 95.50 337.15 m 94.49 334.54 l 93.42 331.76 l 92.31 328.84 l 91.16 325.81 l 90.00 322.69 l 88.84 319.52 l 87.70 316.31 l 86.58 313.10 l 85.52 309.92 l 84.51 306.78 l S 84.51 306.78 m 82.37 300.27 l 80.56 294.57 l 79.02 289.48 l 77.69 284.78 l 76.52 280.29 l 75.44 275.80 l 74.40 271.11 l 73.35 266.01 l 72.21 260.31 l 70.94 253.80 l S 70.94 253.80 m 69.99 248.92 l 69.09 244.00 l 68.23 239.07 l 67.42 234.17 l 66.66 229.33 l 65.96 224.58 l 65.33 219.97 l 64.76 215.53 l 64.26 211.28 l 63.83 207.28 l S 64.26 211.28 m 63.83 207.28 l S 60.83 214.04 m 63.83 207.28 l 68.19 213.26 l S 142.66 230.54 m 142.66 228.53 l 142.66 226.38 l 142.66 224.13 l 142.66 221.79 l 142.66 219.39 l 142.66 216.95 l 142.66 214.50 l 142.66 212.05 l 142.66 209.64 l 142.66 207.28 l S 142.66 209.64 m 142.66 207.28 l S 138.96 213.69 m 142.66 207.28 l 146.37 213.69 l S 0.000 0.000 0.000 RG 132.33 283.52 m 132.75 281.51 l 133.24 279.37 l 133.78 277.11 l 134.37 274.78 l 134.99 272.38 l 135.63 269.94 l 136.27 267.48 l 136.92 265.04 l 137.54 262.62 l 138.14 260.26 l S 137.54 262.62 m 138.14 260.26 l S 132.98 265.57 m 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