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A Combination of screening and computational approaches for the identification of novel compounds that decrease mast cell degranulation

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Academic year: 2021

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(6) Supplementary Figure 1. Compounds reduced both T308 and S473 phosphorylation of Akt in unstimulated RBL-2H3 cells and there is no decrease in Akt phosphorylation in compounds that show no decrease in degranulation. A.. B.. Ě ƌ ƚĞ Ě ŶĞ ŝƚŽ Ğ ŝ ď ŝ ƚ Ɛ ŵ ƵůĂ ĞĨŽ 5Y2 7Y 9Y 5Y /ŶŚ Ɵ ƚ Ɛ ŵ ŝů 5 0 9 7 Ŭ hŶ ^Ɵ D J5 J6 J6 J7 ^LJ Ă Ƶů. -. +. - - - - - -. pAkt-T308 tAkt pAkt-S473 tAkt. C..

(7) Supplementary Table 1: Degranulation Assay Results and Safety Index Ranking compound J702Y J584E J555Y J521Y J676Y J597E J539C J589E J608E J647E J682Y J694Y J667Y J678Y J689Y J664Y J595E J475E J438Y J509Y J671Y J530Y J505Y J507Y J491C J532Y J607Y J541E J534E IBS-87 J655Y J656Y J500E J511Y J599E J546Y J623E J520Y J453E J660Y J573Y J670Y J553E J674Y. % control -1.8 0.3 1.0 1.4 1.4 1.4 1.9 2.0 2.0 2.1 2.7 2.9 3.1 3.1 3.4 3.4 4.0 4.0 4.2 4.3 4.7 4.7 4.9 4.9 4.9 5.0 5.0 5.2 5.3 5.4 5.5 5.5 5.9 6.2 6.3 7.0 7.0 7.1 7.2 7.2 7.5 7.8 7.9 8.2. % inhibition 101.8 99.7 99.0 98.6 98.6 98.6 98.1 98.0 98.0 97.9 97.3 97.1 96.9 96.9 96.6 96.6 96.0 96.0 95.8 95.7 95.3 95.3 95.1 95.1 95.1 95.0 95.0 94.8 94.7 94.6 94.5 94.5 94.1 93.8 93.7 93.0 93.0 92.9 92.8 92.8 92.5 92.2 92.1 91.8. at conc (µM) 25 25 25 10 25 25 10 25 25 25 25 25 25 25 25 25 10 25 15 25 25 10 25 25 25 25 25 25 10 25 25 25 25 25 25 10 25 25 25 25 25 25 25 25. J683Y. 8.6. 91.4. 25. J673Y J557E J680Y IBS-11 J590Y J663Y J620Y J626Y. 9.2 9.2 9.3 9.4 10.0 10.0 11.0 11.0. 90.8 90.8 90.7 90.6 90.0 90.0 89.0 89.0. 25 25 25 25 25 25 25 25.

(8) J524Y J693Y J699Y J550E J567E J575Y J614Y J637Y J528E J576E J549E J649Y J473C J545E J533Y J554Y J677Y Miltefosine J653Y J688Y J514E J686Y J606E J619Y J625E J714Y IBS-16 J661Y J588Y J629E J692Y J525E J448E J551E J566E J668Y J583E J601Y J627E J687Y J598E J697Y J585Y J538E J684Y J600E J622Y J444C J577E J479Y J645E J666Y J547E J578Y J610Y J644Y. 11.1 11.4 11.5 11.9 12.0 12.0 12.0 12.0 12.1 12.3 12.3 12.5 12.7 12.9 13.0 13.0 13.1 13.2 13.3 13.4 13.5 14.0 14.0 14.0 14.0 14.5 14.6 14.8 15.0 15.0 15.0 15.1 15.3 15.4 15.4 15.8 16.0 16.0 16.0 16.0 16.2 16.4 16.5 16.5 16.8 16.9 17.0 17.4 17.4 17.5 18.0 18.1 18.1 18.5 19.0 19.0. 88.9 88.6 88.5 88.1 88.0 88.0 88.0 88.0 87.9 87.7 87.7 87.5 87.3 87.1 87.0 87.0 86.9 86.8 86.7 86.6 86.5 86.0 86.0 86.0 86.0 85.5 85.4 85.2 85.0 85.0 85.0 84.9 84.7 84.6 84.6 84.2 84.0 84.0 84.0 84.0 83.8 83.6 83.5 83.5 83.2 83.1 83.0 82.6 82.6 82.5 82.0 81.9 81.9 81.5 81.0 81.0. 25 25 25 10 25 25 25 25 25 10 10 25 25 10 10 25 25 10 25 25 25 25 25 25 25 25 25 25 10 25 25 25 25 10 10 25 10 25 25 25 25 25 25 25 25 25 25 25 10 25 25 25 10 10 25 25.

(9) J669Y J651E J556Y J609E J616E J707Y J665Y J681Y IBS-68 J488Y J635E J720Y J429E J657E J632E IBS-63 J612C J703Y J558E J634E J522E J543Y J480Y J548Y J604E J569E J594E IBS-64 J675Y J621E J711Y J658E J477C J679Y J455Y J552E J709Y IBS-41 J484C IBS-15 J469Y IBS-105 J698Y J690C J615E J624E J672Y J712Y J628E J646E J706Y J718Y J633E J700E IBS-44 J705Y. 19.3 19.9 20.0 20.0 20.0 20.2 20.2 20.3 20.7 21.0 21.0 21.1 21.2 22.8 23.0 23.5 24.0 24.5 24.9 25.0 25.8 26.0 26.3 26.5 26.5 26.6 28.3 28.4 28.5 29.0 29.3 29.5 29.8 29.9 30.4 31.9 32.7 33.8 34.0 34.0 35.0 35.3 36.1 36.1 37.0 37.0 37.3 38.2 39.0 39.2 39.3 40.2 41.0 41.7 45.2 46.7. 80.7 80.1 80.0 80.0 80.0 79.8 79.8 79.7 79.3 79.0 79.0 78.9 78.8 77.2 77.0 76.5 76.0 75.5 75.1 75.0 74.2 74.0 73.7 73.5 73.5 73.4 71.7 71.6 71.5 71.0 70.7 70.5 70.2 70.1 69.6 68.1 67.3 66.2 66.0 66.0 65.0 64.7 63.9 63.9 63.0 63.0 62.7 61.8 61.0 60.8 60.7 59.8 59.0 58.3 54.8 53.3. 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 10 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25.

(10) IBS-65 J654Y J704Y IBS-23 IBS-83 J497Y J586E J462E J419E J562Y J431Y J485E IBS-101 J602E IBS-104 J715Y J640E J540C J641E J710Y J568E KA-4 J713Y IBS-42 J518Y J443E J460Y J708Y J648E IBS-66 J478C J636Y J652E J529E J603E J537E J685Y J592C J476S J719Y J650Y KA-5 J519Y KA-3 KA-2 J542E IBS-46 J696Y J531Y KA-52 J605Y J563Y IBS-17 J482C IBS-24 KA-10. 48.5 49.2 50.8 51.9 52.1 53.0 53.7 54.0 57.9 60.3 63.0 63.0 63.5 64.9 65.6 65.8 66.1 66.5 67.0 67.3 67.7 67.8 67.9 68.0 68.4 69.0 69.0 70.4 70.7 70.7 71.0 72.0 72.9 73.0 73.2 73.3 73.4 74.2 76.0 76.3 76.3 76.8 77.3 77.5 78.2 79.0 79.5 79.7 80.7 81.7 83.5 84.3 84.5 85.0 85.4 85.9. 51.5 50.8 49.2 48.1 47.9 47.0 46.3 46.0 42.1 39.7 37.0 37.0 36.5 35.1 34.4 34.2 33.9 33.5 33.0 32.7 32.3 32.2 32.1 32.0 31.6 31.0 31.0 29.6 29.3 29.3 29.0 28.0 27.1 27.0 26.8 26.7 26.6 25.8 24.0 23.7 23.7 23.2 22.7 22.5 21.8 21.0 20.5 20.3 19.3 18.3 16.5 15.7 15.5 15.0 14.6 14.1. 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25.

(11) J405S J565Y J461Y J506Y IBS-45 IBS-20 IBS-97 J593C J494E KA-7 J662C IBS-35 IBS-50 IBS-56 J570E IBS-79 KA-38 IBS-96 J643Y IBS-43 J596C J495Y KA-53 J572E J571E IBS-98 IBS-106 J510Y J428E J508Y KA-33 KA-6 KA-9 KA-32 KA-23 KA-31 KA-22 IBS-36 IBS-85 J580Y J454E J489Y IBS-30 J611Y J613C KA-12 J659Y IBS-58 J617E J503E J501E KA-50 KA-37 J439S KA-27 IBS-21. 85.9 86.0 87.0 87.0 87.1 87.1 87.6 87.8 88.6 89.4 89.5 89.5 89.5 89.7 90.0 90.1 90.2 90.2 90.7 90.7 90.9 90.9 90.9 91.0 91.1 91.1 91.5 91.7 91.9 92.5 92.6 92.7 93.0 93.2 93.5 93.5 93.7 94.0 94.4 94.4 95.0 95.0 95.1 95.1 95.2 95.4 95.5 95.9 96.0 96.0 96.3 96.9 96.9 96.9 97.0 97.8. 14.1 14.0 13.0 13.0 12.9 12.9 12.4 12.2 11.4 10.6 10.5 10.5 10.5 10.3 10.0 9.9 9.8 9.8 9.3 9.3 9.1 9.1 9.1 9.0 8.9 8.9 8.5 8.3 8.1 7.5 7.4 7.3 7.0 6.8 6.5 6.5 6.3 6.0 5.6 5.6 5.0 5.0 4.9 4.9 4.8 4.6 4.5 4.1 4.0 4.0 3.7 3.1 3.1 3.1 3.0 2.2. 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 100 100 25 25 25 25 25.

(12) IBS-2 J449E IBS-103 J582C J447C J430S J536Y J502E J564Y KA-30 J631Y J559S IBS-102 J486Y KA-36 J437Y J561Y IBS-49 IBS-100 KA-14 KA-25 J560S J639E KA-34 IBS-33 KA-29 J515Y IBS-47 J513E J591E KA-26 IBS-34 KA-28 KA-17 J459Y IBS-95 KA-13 J523E KA-24 KA-42 J483C IBS-107. 97.8 98.0 98.1 98.3 98.6 99.2 99.4 99.4 99.5 99.8 100.0 100.3 100.7 101.0 101.2 101.4 101.7 102.0 102.7 102.7 103.0 103.1 103.3 103.7 103.7 104.2 104.3 104.8 105.5 105.6 106.0 107.7 108.8 108.8 109.0 109.1 109.2 110.5 112.0 114.8 115.0 132.1. 2.2 2.0 1.9 1.7 1.4 0.8 0.6 0.6 0.5 0.2 0.0 -0.3 -0.7 -1.0 -1.2 -1.4 -1.7 -2.0 -2.7 -2.7 -3.0 -3.1 -3.3 -3.7 -3.7 -4.2 -4.3 -4.8 -5.5 -5.6 -6.0 -7.7 -8.8 -8.8 -9.0 -9.1 -9.2 -10.5 -12.0 -14.8 -15.0 -32.1. 25 25 25 25 25 25 25 100 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25.

(13) Safety Index Ranking.  . . . . . . . . . . . . . .   . . . . . . . . . . . . . . . . . . . . .  . . . . . . . .       .  .                                                                                                         .  

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(211)  $ % ' ( ) * + , $# $$.     .      .   ' !(   ' "!(    "' !(  "' "!(  "  "' !(  "' "!(  "    ' !(    ' "!(                                                        .      .   ' !(   ' "!(    "' !(  "' "!(  "  "' !(  "' "!(  "    ' !(    ' "!(                                                   

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(214) Supplementary Table 3: Endocytic Profiles (compounds with parameters in bold are endocytic hits). Ag1478_10 Dmso 0.1% Miltefosine IBS-100 IBS-101 IBS-102 IBS-103 IBS-104 IBS-105 IBS-106 IBS-107 IBS-11 IBS-15 IBS-16 IBS-17 IBS-2 IBS-20 IBS-21 IBS-23 IBS-24 IBS-30 IBS-33 IBS-34 IBS-35 IBS-36 IBS-41 IBS-42 IBS-43 IBS-44 IBS-45 IBS-46 IBS-47 IBS-49 IBS-50 IBS-56 IBS-58 IBS-63 IBS-64 IBS-65 IBS-66 IBS-68 IBS-79 IBS-83 IBS-85 IBS-87 IBS-95. EGF number EGF mode EGF mode of vesicle Area (volume Area (mean masked weighted) int. weighted) 2.277 4.573 7.175 -0.194 -0.423 -0.733 0.357 -0.299 -0.129 0.188 -0.138 0.298 0.698 -0.671 -0.200 0.391 -0.509 0.142 0.993 -0.133 0.129 0.830 0.110 0.426 0.548 0.436 1.068 0.660 0.439 1.020 0.225 -1.359 -0.440 -0.585 0.579 0.048 -1.239 0.140 -0.017 0.260 -0.478 -0.809 -1.360 2.574 3.290 0.013 -0.616 -0.225 0.567 -0.373 -0.135 -0.166 0.077 -0.077 0.613 -0.902 -0.509 0.251 -0.198 -0.905 0.121 0.439 -0.041 -0.517 -0.303 1.351 -1.141 -0.220 -0.847 -1.557 -0.198 0.246 -0.282 -0.434 -0.555 0.113 -0.227 -0.210 -1.329 0.626 0.384 -1.043 0.644 -0.065 -0.393 0.196 -0.229 -0.254 -0.706 -1.079 0.321 -0.955 -1.227 -1.753 0.956 2.230 -0.962 0.988 0.344 -2.331 1.410 0.890 -1.886 1.938 2.859 -0.681 -0.352 0.576 -0.851 -0.120 0.443 -0.567 -0.054 0.752 -0.549 -0.435 -0.767 -0.226 0.243 0.380 1.924 -0.488 0.215 -0.337 -0.346 -0.012 -0.967 0.505 0.891 0.439 -0.476 0.324 2.565 -1.718 -1.064 1.338 -1.367 -0.671.       . EGF mode Area 2.762 -0.509 -0.271 -0.037 -0.481 0.045 0.356 0.042 0.631 0.375 -0.473 0.000 0.040 -0.450 2.408 -0.153 -0.284 -0.107 -0.633 -0.388 0.025 0.399 -0.497 0.124 -0.429 -0.132 0.352 0.291 -0.536 -0.608 -0.942 0.949 0.609 0.895 1.570 0.110 0.298 -0.031 -0.228 0.127 -0.389 -0.311 0.333 -0.078 -1.086 -0.961. 

(215)  !. EGF mode Mean Intensity (volume weighted) -2.824 0.000 2.112 0.254 1.561 1.380 0.612 1.902 0.088 0.762 1.318 -0.296 -0.780 -0.177 -1.227 0.503 -0.102 0.070 0.396 -0.241 -0.224 0.866 -1.090 -0.434 -0.766 -0.343 -0.744 -0.767 -1.072 0.438 1.185 -1.324 -1.226 -1.385 -1.471 -0.205 -0.717 0.151 -0.029 0.199 2.229 1.712 -1.214 0.330 2.077 1.864. EGF mode Mean Intensity (mean int. weighted) -2.556 0.059 1.286 0.368 1.262 1.319 0.676 1.550 0.300 0.794 1.237 -0.257 -0.728 0.046 -1.015 0.720 0.289 0.154 0.383 -0.131 -0.058 0.883 -0.770 -0.256 -0.771 0.084 -0.621 -0.550 -0.932 0.597 1.655 -1.082 -1.023 -1.083 -1.319 0.045 -0.655 0.550 0.073 0.222 1.616 1.619 -0.810 0.670 1.947 1.660.

(216) IBS-96 IBS-97 IBS-98 J405S J419E J428E J429E J430E J431Y J437Y J438Y J439S J443E J444C J447C J448E J449E J453E J454E J455Y J459Y J460Y J461Y J462E J469Y J473C J475E J476S J477C J478C J479Y J480Y J482C J483C J484C J485E J486Y J488Y J489Y J491C J494E J495Y J497Y J500E J501E J502E J503E J505Y J506Y J507Y J508Y J509Y J510Y. 0.662 1.010 0.648 0.747 -0.818 0.707 0.115 0.436 0.169 1.017 1.181 0.467 -0.078 1.433 0.027 0.934 0.896 0.854 0.668 1.905 0.466 -0.204 -1.146 -0.266 -0.138 -1.246 0.679 -0.294 0.022 -0.326 -0.522 0.746 -0.357 -0.001 0.286 0.748 -0.010 0.267 -0.021 -1.269 0.019 -0.558 -0.706 -0.223 -0.294 -0.624 -0.543 0.345 -0.054 -0.825 -1.280 -0.496 -1.524. -0.128 -1.353 -0.176 0.346 2.881 -0.234 0.673 0.701 -0.182 -0.567 1.366 0.074 2.263 -1.194 1.113 -0.743 0.362 1.289 0.471 -1.242 -0.101 0.131 4.815 -0.155 0.708 2.305 -0.933 -0.252 -0.071 0.072 3.255 -0.437 0.552 0.351 -0.548 -1.577 0.078 -0.560 -0.220 0.387 -0.904 0.611 0.734 0.622 -0.046 -0.167 -0.992 2.125 0.534 2.394 1.785 1.917 2.460.       . -0.304 -0.686 0.716 0.609 1.868 -0.002 0.601 0.930 -0.075 -0.325 1.902 0.462 2.391 -0.706 1.335 -0.430 0.932 1.104 0.950 -0.724 -0.145 -0.254 4.659 -0.758 0.206 1.439 -0.733 -0.098 -0.347 -0.049 3.194 -0.368 0.012 -0.044 -0.816 -1.487 -0.108 -0.170 -0.090 0.180 -1.399 0.144 -0.046 -0.216 -0.214 0.195 -0.546 1.171 0.538 1.244 0.963 0.875 1.302. 

(217)  !. -0.559 -0.872 0.003 0.681 2.352 0.216 0.942 1.192 0.136 -0.779 1.023 0.330 2.734 -0.854 1.532 -0.593 1.172 1.068 0.944 -1.189 0.281 0.113 5.393 -0.524 0.254 2.221 -1.089 0.173 -0.342 0.254 2.986 -0.514 0.809 0.306 -0.880 -1.790 -0.047 -0.675 -0.059 0.926 -1.367 0.799 0.357 0.000 -0.103 0.273 -0.574 0.819 0.293 1.645 1.874 1.147 2.016. 1.358 2.296 0.636 0.736 -1.270 1.492 -0.834 0.186 0.584 1.603 -0.231 0.179 -0.242 1.294 0.646 0.407 1.194 -0.889 0.346 4.199 0.015 -0.787 -1.443 -0.646 -1.063 -1.162 0.845 -0.429 0.347 0.228 -1.103 0.380 -0.802 -0.542 0.016 1.509 0.241 0.923 -0.142 -0.326 0.304 -1.098 -1.033 -0.504 -0.281 0.141 0.831 -0.723 0.071 -1.174 -1.494 -0.910 -1.238. 1.265 1.827 0.785 0.585 -1.228 2.444 -0.425 0.573 0.695 2.084 -0.674 0.135 -0.195 1.612 0.847 0.393 1.669 -0.922 1.679 3.674 0.032 -0.602 -1.269 0.160 -0.928 -0.945 0.884 0.091 0.537 0.175 -1.123 0.515 -0.407 -0.390 0.042 2.050 0.323 0.530 -0.048 -0.398 0.318 -0.895 -0.894 -0.574 -0.239 0.230 1.280 -0.863 0.006 -1.208 -1.364 -1.018 -1.158.

(218) J511Y J513Y J514E J515Y J518Y J519Y J520Y J521Y J522E J523E J524Y J525E J528E J529E J530Y J531Y J532Y J533Y J534E J536Y J537E J538E J539C J540C J541E J542E J543Y J545Y J546Y J547E J548Y J549E J550E J551E J552E J553E J554Y J555Y J556Y J557E J558E J559S J560S J561Y J562Y J563Y J564Y J565Y J566E J567E J568E J569E J570E. -1.156 -1.354 -0.593 0.069 0.841 1.256 0.993 0.343 0.718 0.863 0.513 0.796 -0.736 0.291 0.878 0.213 -0.356 0.926 1.745 0.771 -0.618 -0.216 -0.494 -0.751 -0.986 0.182 -0.049 -0.647 -0.193 -0.372 -0.018 0.884 0.455 0.317 0.132 -0.550 -0.018 0.698 -0.279 -0.179 -0.550 -1.083 -0.595 -1.214 -0.466 -0.310 -1.217 -0.154 -1.323 -0.908 -0.645 -2.352 -1.185. 1.287 0.535 0.048 0.354 -0.283 -0.292 -0.375 2.406 0.446 -1.142 0.002 3.702 4.111 1.158 -0.340 0.791 2.008 -0.460 -0.494 -1.334 1.565 0.968 3.893 0.625 4.557 0.517 3.438 2.085 1.478 -0.392 -0.725 0.065 -0.410 1.110 0.229 0.718 -0.779 -0.424 1.349 0.397 -0.146 1.401 3.051 0.838 0.119 -0.552 0.544 -1.174 3.591 0.796 -0.655 6.377 2.253.       . 1.187 0.665 -0.104 0.827 0.198 0.272 0.008 0.947 -0.261 -1.097 -0.360 3.813 4.129 1.922 -0.074 0.370 1.872 -0.239 -0.328 -0.588 0.940 0.519 3.157 0.400 3.132 0.203 1.992 1.701 0.663 -0.515 -0.613 0.165 -0.632 0.401 0.133 0.375 -0.851 -0.839 1.101 -0.050 -1.081 0.968 2.843 -0.435 -0.024 -0.443 0.448 -0.880 2.969 -0.423 -0.796 6.525 1.915. 

(219)  !. 1.250 0.911 -0.217 1.338 0.028 0.234 -0.387 1.200 0.075 -1.155 -0.196 2.757 4.919 2.443 -0.086 0.764 1.896 -0.484 -0.707 -0.575 1.378 0.740 3.313 0.351 3.380 0.626 2.128 2.445 1.508 -0.472 -0.931 -0.098 -0.923 0.353 0.523 0.635 -0.767 -0.810 1.382 0.206 -0.937 1.578 3.709 0.508 0.256 -0.515 0.839 -0.991 3.006 -0.010 -0.571 6.243 2.304. -0.874 -0.602 0.776 -0.688 0.621 1.589 1.267 -1.263 -0.707 1.582 -1.000 -1.240 -1.103 -0.539 0.918 -0.756 -1.084 -0.097 0.618 2.106 -0.723 -0.345 -1.195 -0.538 -1.355 -0.131 -1.185 -1.137 -1.066 -0.336 0.907 0.115 -0.134 -0.814 -0.517 -0.522 -0.402 -0.081 -0.788 -0.049 -0.569 -1.176 -1.233 -0.727 -0.135 0.240 -0.471 0.936 -1.473 -1.180 -0.602 -1.722 -0.649. -0.934 -0.390 0.246 -0.215 0.688 1.772 1.022 -1.309 -0.740 1.985 -0.943 -1.458 -1.131 -0.022 0.810 -0.583 -1.027 0.051 0.375 2.387 -0.752 -0.530 -1.299 -0.206 -1.329 0.080 -1.222 -1.133 -0.954 0.079 0.692 0.219 -0.069 -0.926 -0.481 -0.497 -0.256 -0.169 -0.459 -0.166 -0.565 -1.028 -1.173 -0.630 -0.044 0.301 -0.472 0.872 -1.428 -1.080 -0.494 -1.709 -0.608.

(220) J571E J572E J573Y J575Y J576E J577E J578Y J580Y J582C J583E J584E J585Y J586E J588Y J589E J590Y J591E J592C J593C J594E J595E J596C J597E J598E J599E J600E J601Y J602E J603E J604E J605Y J606E J607Y J608E J609E J610Y J611Y J612Y J613C J614Y J615E J616E J617E J619Y J620Y J621E J622Y J623E J624E J625E J626Y J627E J628E. -1.605 -0.794 -0.300 -0.792 -0.465 -0.367 0.275 0.374 0.753 -0.516 1.664 0.516 -0.477 -1.167 1.207 0.319 -0.628 -0.517 0.154 1.127 -0.365 0.743 0.100 1.228 0.180 -0.935 -0.530 0.907 -0.323 -1.010 -0.007 -0.164 0.363 -0.344 -0.322 -1.122 -0.637 0.519 -0.435 -0.315 -0.647 -1.435 -0.533 -1.327 -1.597 -0.297 -0.604 0.316 -0.409 -0.282 -0.029 -1.038 -1.334. 2.519 2.023 -0.174 0.150 2.140 2.569 -0.828 0.543 -1.405 2.681 -1.129 -0.090 1.546 2.823 0.300 0.979 1.229 2.322 0.297 -0.092 2.744 -1.026 0.017 -0.845 -0.293 1.180 0.742 -1.915 0.836 0.900 -1.140 0.474 -0.767 -0.258 0.176 1.690 -0.091 -0.800 1.675 1.046 -0.471 1.100 -0.728 0.358 2.313 -1.493 0.697 -1.025 0.466 0.673 0.429 3.007 1.959.       . 1.952 1.588 -0.754 -0.507 1.540 2.491 -0.498 0.864 -1.141 2.535 -0.644 -0.087 1.910 2.780 0.368 0.594 0.461 1.985 -0.028 -0.109 2.325 -0.631 -0.884 -1.170 -0.258 0.304 -0.341 -1.310 0.073 0.257 -0.768 0.071 -0.918 -1.116 -0.140 0.015 -0.611 -1.290 1.072 0.744 -0.259 0.287 -0.774 -0.555 1.551 -1.496 -0.428 -1.031 0.530 0.620 -0.316 2.104 0.570. 

(221)   !. 2.302 1.664 -0.947 -0.226 1.901 2.063 -0.956 1.448 -1.563 2.627 -0.767 -0.149 2.242 3.221 -0.089 0.635 1.121 2.499 0.472 -0.496 2.323 -0.872 -0.415 -1.493 -0.043 0.665 -0.201 -2.083 0.499 0.374 -0.868 0.066 -1.024 -0.975 0.051 0.713 -0.532 -1.203 1.285 1.035 -0.459 0.974 -0.662 -0.156 2.148 -1.695 -0.471 -0.927 0.861 0.803 -0.294 2.879 1.300. -1.316 -0.474 -0.241 -0.793 -1.166 -0.582 1.688 -0.843 0.373 -0.869 2.773 0.180 -0.999 -1.548 1.098 -0.877 -0.618 -0.756 0.743 0.040 -0.859 5.502 -0.802 -0.007 -0.368 -1.276 -1.251 6.469 -0.949 -0.295 1.610 -0.616 0.799 -0.867 -0.287 -0.968 -0.143 -0.369 -0.450 -0.953 -0.130 -0.976 0.588 -0.976 -1.288 0.462 -0.946 2.886 0.437 -0.885 -0.798 -1.174 -0.978. -1.170 -0.598 -0.348 -0.732 -1.117 -0.768 1.395 -0.555 0.537 -0.190 2.711 0.012 -0.881 -1.504 0.541 -0.949 -0.384 -0.410 0.977 -0.114 -0.982 4.702 -0.671 -0.130 -0.154 -1.122 -1.227 5.569 -0.829 -0.517 1.995 -0.692 0.859 -0.720 0.269 -0.950 -0.287 -0.035 -0.314 -0.811 -0.088 -0.919 0.612 -0.954 -0.669 0.847 -1.018 2.608 0.569 -0.950 -0.864 -1.166 -1.021.

(222) J629E J631Y J632E J633E J634E J635E J636Y J637Y J639E J640E J641E J643Y J644Y J645E J646E J647E J648E J649Y J650Y J651E J652E J653Y J654Y J655Y J656Y J657E J658E J659Y J660Y J661Y J662C J663Y J664Y J665Y J666Y J667Y J668Y J669Y J670Y J671Y J672Y J673Y J674Y J675Y J676Y J677Y J678Y J679Y J680Y J681Y J682Y J683Y J684Y. -0.487 -0.809 -0.319 -1.146 -1.115 -0.113 0.592 -0.197 -0.085 1.969 0.835 0.206 1.008 2.771 0.403 1.192 0.483 0.101 0.807 0.073 1.201 0.250 -0.086 -0.055 0.364 -0.459 1.633 0.149 0.138 0.267 0.284 -0.100 -0.238 0.409 0.250 0.087 0.772 -1.003 0.061 0.333 -0.680 0.076 -0.483 -1.113 0.156 -0.696 -0.856 0.669 0.454 0.013 0.243 0.959 -1.246. 1.039 1.685 0.958 1.197 1.971 0.266 -0.488 2.255 -0.008 -1.542 -0.507 -0.390 -0.734 -0.378 -0.319 -0.020 0.269 0.663 -0.992 0.143 -1.822 -0.049 -1.082 0.820 0.766 0.595 -1.348 -0.988 1.534 0.359 -0.989 0.750 -0.543 -0.266 -0.955 0.657 -0.424 0.352 0.754 1.092 1.336 0.228 -0.726 -0.540 -0.081 0.575 -0.286 -1.305 -0.697 -1.242 -0.074 -0.870 1.095.       . 0.401 1.113 0.401 0.580 1.501 0.347 -0.216 0.290 0.218 -0.782 -0.766 -0.051 -0.221 0.393 -0.455 0.463 0.720 -0.018 -0.612 0.053 -1.028 -0.177 -0.686 0.091 0.267 0.196 -1.234 -1.186 0.895 0.646 -0.582 0.204 -0.694 -0.317 -1.280 0.355 -0.807 -0.249 0.231 0.156 1.429 0.440 -0.946 -0.970 -1.091 -0.195 -0.619 -1.005 -1.234 -1.086 -0.817 -0.901 0.692. 

(223) ! !. 0.412 1.458 1.060 1.277 1.660 0.909 0.043 0.652 0.010 -1.312 -0.569 0.044 -0.469 -0.297 -0.522 0.322 0.989 0.343 -0.652 0.167 -1.614 -0.354 -0.990 0.022 0.417 0.605 -1.683 -1.263 0.983 0.646 -0.638 0.630 -1.034 -0.670 -1.328 0.153 -0.969 0.364 0.310 0.162 1.820 0.206 -0.960 -0.961 -1.003 0.208 -0.746 -1.503 -1.215 -1.188 -0.706 -1.259 1.165. -0.772 -1.264 -0.721 -0.590 -1.060 -0.360 0.744 -1.299 0.695 4.633 0.053 0.680 2.842 1.185 1.734 1.623 -0.130 -1.097 0.744 -0.120 3.637 1.409 2.314 -0.964 -0.390 -1.114 3.852 0.001 -1.058 1.079 1.196 0.028 0.272 1.075 0.071 -0.598 -0.224 -1.274 -0.509 -0.931 -0.711 1.084 -0.128 -0.103 -0.738 -1.090 -0.509 1.226 -0.356 0.351 -0.786 0.374 -1.359. -0.738 -1.173 -0.630 -0.544 -1.010 -0.070 1.009 -1.331 1.012 4.342 0.478 1.522 3.141 0.663 1.926 1.923 0.337 -1.115 1.127 0.006 3.375 0.930 2.051 -0.984 -0.531 -0.827 3.068 0.449 -1.110 0.859 1.777 0.046 -0.030 1.018 0.082 -0.755 -0.217 -1.178 -0.415 -1.028 -0.656 0.641 -0.151 -0.255 -0.719 -0.982 -0.656 1.027 0.213 0.052 -0.741 0.108 -1.232.

(224) J685Y J686Y J687Y J688Y J689Y J690C J692Y J693Y J694Y J696Y J697Y J698Y J699Y J700E J702Y J703Y J704Y J705Y J706Y J707Y J708Y J709Y J710Y J711Y J712Y J713Y J714Y J715Y J718Y J719Y J720Y J775Y KA-10 KA-12 KA-13 KA-14 KA-17 KA-2 KA-22 KA-23 KA-24 KA-25 KA-26 KA-27 KA-28 KA-29 KA-3 KA-30 KA-31 KA-32 KA-33 KA-34 KA-36. -0.663 -1.877 -0.966 0.257 -1.262 -0.460 0.726 1.684 0.230 0.842 1.844 0.931 1.349 0.582 1.397 -1.314 1.042 -0.904 0.106 0.946 -0.741 0.862 0.318 -0.443 0.923 0.709 1.700 -0.184 0.608 0.746 1.435 0.339 0.393 0.330 0.228 -0.729 -0.932 -0.117 0.032 1.162 -0.132 -0.293 -0.044 -0.308 1.129 -0.456 0.130 -0.957 -1.634 -1.273 -0.912 -0.310 -0.555. 0.316 2.923 0.661 -0.592 1.361 -0.843 -0.032 -0.255 -0.884 -0.598 -1.454 -0.722 -1.316 -0.898 0.291 0.341 -0.073 0.480 -0.564 -0.919 -0.908 -0.551 -0.060 -0.104 -0.654 -0.520 -0.695 1.340 -1.150 -0.172 -0.824 -0.613 -1.075 -0.186 0.298 -0.754 0.165 -0.048 0.422 -0.545 -0.243 -0.436 -0.250 -0.324 -0.538 0.016 0.229 -0.674 0.532 0.200 -0.494 0.755 -0.272.       . 0.071 2.655 0.079 -0.921 1.008 -1.241 0.051 -0.322 -0.260 0.757 -0.662 -0.156 -1.067 -0.317 0.837 1.082 0.019 0.951 0.332 -0.870 -0.201 -0.409 -0.100 -0.475 -0.445 -0.545 -0.785 1.990 -1.150 -0.678 -0.507 0.015 -0.680 -0.644 0.586 -0.903 -0.042 0.065 0.230 0.102 -0.938 -0.435 0.115 -0.756 -0.140 0.066 0.391 -0.601 0.819 -0.464 -0.868 1.336 -0.251. 

(225) " !. 0.467 3.447 0.271 -1.154 1.530 -1.058 -0.303 -0.372 -0.653 0.213 -0.773 -0.360 -1.016 -0.474 0.095 0.305 -0.292 0.525 -0.027 -0.768 -0.298 -0.448 0.257 -0.331 -0.870 -0.758 -0.500 0.972 -0.970 -0.261 -0.459 -0.234 -0.636 -0.422 0.005 -0.526 -0.294 0.181 0.388 0.792 -0.386 -0.065 -0.061 -0.378 -0.468 -0.012 0.257 -0.453 0.333 -0.122 -0.206 0.789 -0.682. -1.204 -1.104 -0.976 0.291 -0.617 0.075 0.482 0.221 -0.151 0.728 1.545 1.289 0.841 2.726 -1.211 -0.596 2.672 -0.181 0.820 1.430 1.591 1.080 1.239 1.089 0.362 2.553 -0.278 -0.486 0.883 -0.111 1.104 2.920 1.318 1.195 -0.495 0.070 -0.529 0.643 -0.637 5.331 0.327 0.906 0.438 2.115 1.894 -0.208 -0.189 -0.061 -0.807 -0.619 -0.692 -0.529 0.262. -0.919 -0.854 -0.724 -0.098 -0.225 0.047 0.623 0.265 -0.058 1.136 1.653 1.363 1.177 2.485 -0.852 -0.272 2.245 -0.183 0.750 1.222 1.536 1.215 1.329 1.131 0.586 1.937 -0.064 -0.281 0.827 0.138 0.857 1.786 1.757 1.438 -0.388 0.094 -0.549 0.720 -0.429 4.465 0.412 0.674 0.572 1.989 2.065 0.074 -0.032 -0.065 -0.649 -0.340 -0.336 -0.383 0.477.

(226) KA-37 KA-38 KA-4 KA-42 KA-5 KA-50 KA-52 KA-53 KA-6 KA-7 KA-9. -0.729 -0.591 0.239 -1.279 -1.382 -0.004 -1.619 -0.797 0.011 -0.857 -0.528. -0.175 0.101 -0.462 0.655 0.945 -0.169 -0.301 -0.306 -0.940 0.373 0.279.       . 0.184 0.019 -0.797 0.725 1.355 -1.072 -0.422 -0.563 -0.949 0.297 0.536. 

(227) # !. -0.049 -0.175 -0.429 0.538 0.558 -0.058 0.185 -0.351 -0.664 -0.055 0.931. -0.148 -0.392 0.686 -0.952 -0.511 0.012 -0.729 0.406 0.381 -0.599 -0.484. 0.004 -0.314 0.674 -0.620 -0.270 0.138 -0.566 0.298 0.561 -0.436 -0.364.

(228) ). EGF mode Mean Intensity -1.692 0.258 1.211 0.160 0.658 0.862 0.243 0.573 -0.131 0.320 1.062 -0.617 -0.696 -0.010 -1.216 0.458 0.250 -0.090 0.374 -0.182 0.075 0.742 -0.680 -0.082 -0.295 -0.101 -0.611 -0.748 -0.774 0.273 1.935 -0.745 -1.054 -0.465 -1.124 0.118 -0.256 0.298 0.206 0.062 1.546 1.121 -0.622 -0.164 1.070 1.146. EGF mode Integral intensity (volume weighted) -0.761 -0.383 2.368 0.121 1.553 2.134 0.569 1.167 0.701 1.186 1.108 -0.183 -0.706 0.468 -0.767 0.468 0.054 -0.110 0.866 -0.273 -0.160 1.382 -0.594 -0.535 -0.770 0.051 -0.632 -0.849 -0.518 0.240 1.645 -1.026 -0.865 -0.924 -0.949 -0.226 -1.016 0.191 0.056 0.034 2.117 1.777 -0.670 0.584 2.111 1.837. EGF mode Integral intensity (mean int. weighted) -1.318 -0.322 1.323 0.250 2.093 2.626 1.426 1.393 1.171 1.399 1.159 0.098 -0.763 0.544 -0.881 0.654 0.099 0.075 1.124 -0.314 -0.007 2.165 -0.486 -0.433 -0.674 0.087 -0.683 -0.912 -0.522 0.588 2.280 -0.894 -0.919 -0.731 -0.700 -0.255 -0.907 0.432 0.342 0.126 3.001 2.288 -0.623 0.907 3.282 2.335.       . EGF mode Integral intensity -1.889 -0.148 2.214 0.684 0.771 1.843 1.082 1.223 0.388 1.029 0.988 -0.918 -0.582 -0.810 -0.300 0.973 0.185 0.045 0.211 -0.216 0.175 1.427 -1.351 0.078 -0.788 -0.903 -0.632 -0.652 -1.948 0.315 1.778 -0.590 -1.127 -0.095 -0.818 0.269 -0.291 0.338 0.280 0.278 1.751 1.864 -0.877 -0.061 0.218 1.014. EGF Dist. to nuc. (volume weigted | nuc. size normalized) 5.419 -0.674 -0.518 -0.019 0.747 -0.295 2.079 0.328 0.236 0.430 0.367 0.899 -0.096 -0.249 1.942 -0.635 1.152 1.941 0.770 -0.267 -0.437 -0.490 2.685 1.981 1.857 1.876 1.957 0.752 2.077 2.407 2.302 2.467 2.773 -0.063 0.640 1.614 1.030 1.580 1.401 -0.020 -0.701 -2.115 -0.064 -1.294 0.482 0.939. 

(229) $ !. EGF Dist. to nuc. (mean EGF Dist. to int. weighted nuc. (nuc. | nuc. size size normalized) normalized) 4.157 3.441 -0.657 -0.408 -0.310 0.058 0.177 1.258 0.804 1.213 -0.182 0.928 1.790 1.993 0.277 1.367 0.234 0.903 0.559 1.814 -0.166 1.103 1.101 0.891 0.175 -0.223 0.187 0.429 1.296 0.988 -0.320 0.171 0.918 1.797 1.818 2.000 0.961 1.562 -0.018 0.057 -0.072 0.393 -0.318 -0.489 2.995 3.308 2.620 1.272 1.991 3.279 1.919 2.546 1.994 2.223 1.048 0.618 1.910 2.700 2.556 3.846 2.106 3.536 1.908 1.122 1.935 0.951 -0.110 -0.906 0.603 0.393 1.356 1.408 0.764 0.885 1.335 1.626 1.612 2.034 -0.056 0.027 -0.319 0.440 -1.541 -0.927 -0.108 -0.694 -1.198 -0.058 0.718 2.502 0.793 1.764.

(230) 1.045 1.801 0.076 0.492 -1.623 0.991 -0.806 -0.091 0.558 1.221 -0.429 0.144 -0.391 1.572 0.272 0.412 0.740 -1.015 0.846 3.375 0.092 -0.693 -2.116 -0.463 -1.114 -1.476 0.926 -0.200 0.108 0.670 -1.423 0.445 -0.917 -0.597 -0.092 1.481 0.207 0.875 0.170 -0.668 0.907 -1.080 -1.024 -0.345 -0.372 -0.242 0.825 -0.722 0.340 -1.347 -1.840 -1.268 -1.690. 1.408 1.974 1.954 1.939 -0.525 3.006 0.383 1.226 1.520 2.487 0.295 1.161 0.416 1.991 2.575 0.813 2.661 -0.893 1.992 5.895 0.325 0.096 -0.395 0.324 -0.654 -0.384 1.677 1.122 1.570 0.807 -0.495 0.894 0.176 0.278 0.689 2.620 0.585 1.426 0.446 -0.236 0.101 -0.649 -0.610 -0.573 0.126 0.165 1.769 -0.787 0.524 -1.370 -1.415 -1.136 -1.064. 1.589 2.620 1.964 1.477 -0.632 3.102 0.355 1.004 1.365 2.116 -0.675 0.559 0.359 1.952 1.616 0.311 2.681 -0.849 1.816 4.075 0.505 -0.253 -0.373 0.235 -0.604 -0.448 1.058 1.037 0.814 0.519 -0.708 0.589 0.181 -0.064 0.275 1.938 0.478 0.664 0.111 -0.254 -0.055 -0.545 -0.563 -0.760 0.006 0.027 1.383 -1.188 0.167 -1.499 -1.283 -1.206 -0.950.       . 1.417 1.811 -0.055 1.887 -0.146 2.603 0.802 1.666 1.594 1.959 -0.559 0.806 1.283 1.946 2.296 0.569 3.226 -1.000 2.376 3.495 0.754 0.060 0.479 0.466 -0.402 0.055 1.221 1.227 0.835 1.207 0.112 0.515 0.569 0.127 0.385 1.459 0.850 0.945 0.462 0.334 0.387 -0.242 -0.579 -0.424 0.182 0.255 1.111 -1.189 0.846 -1.406 -1.511 -1.349 -0.899. 

(231) % !. -0.274 -0.121 -0.668 -1.018 -0.480 0.042 0.118 -0.702 0.863 -0.328 2.808 -0.124 -0.326 -0.210 -0.166 0.080 -0.520 0.453 0.389 0.586 0.207 0.459 -0.339 0.294 0.997 0.524 -0.720 0.190 -0.123 0.367 0.712 0.096 -0.230 1.107 0.293 0.638 1.198 0.678 1.448 0.246 1.644 0.388 0.568 2.365 0.310 1.214 1.652 3.316 0.618 2.336 0.197 2.364 0.560. -0.191 0.089 -0.700 -0.762 -0.476 -0.030 0.056 -0.663 0.731 0.093 2.845 0.273 -0.344 -0.047 -0.075 -0.015 -0.441 0.771 0.399 0.794 0.502 0.520 -0.526 0.293 0.974 0.675 -0.405 0.180 0.084 0.581 0.444 0.263 -0.024 1.038 0.560 0.785 1.402 0.953 1.364 0.395 1.538 0.152 0.537 2.147 0.252 1.272 1.750 3.027 0.476 2.147 0.286 2.852 0.855. 0.210 0.849 0.119 -0.859 -0.715 -0.445 -0.296 -0.658 0.713 0.400 1.737 -0.068 -0.605 -0.107 -0.565 0.039 -0.601 0.375 -0.117 0.971 0.336 0.267 -0.891 0.030 0.828 0.073 -0.258 -0.050 0.039 0.201 0.127 0.037 -0.489 0.561 0.545 0.800 1.348 0.883 1.252 0.261 1.183 -0.468 0.274 1.417 0.463 0.956 1.418 1.908 0.113 1.292 -0.210 2.176 0.463.

(232) -0.923 -0.452 0.603 -0.341 0.615 1.414 1.069 -1.683 -0.675 1.681 -1.206 -2.050 -1.371 -0.294 0.521 -0.779 -1.453 0.057 1.258 1.755 -1.447 -0.365 -1.732 -0.599 -1.994 -0.402 -1.536 -1.468 -1.187 -0.212 0.666 0.265 -0.040 -0.923 -0.314 -0.705 -0.067 0.131 -0.856 0.137 -0.485 -1.207 -1.636 -1.117 -0.195 0.360 -0.795 0.407 -2.041 -1.243 -0.346 -2.651 -1.004. -1.103 -0.127 1.922 0.712 1.732 2.972 2.206 -1.321 -0.303 2.476 -1.071 -1.471 0.492 1.546 1.664 0.011 -0.967 0.836 0.790 3.065 -0.621 -0.063 -0.721 1.368 -0.200 0.807 -0.702 -0.530 -0.403 0.471 1.079 0.895 -0.221 -0.887 0.102 0.515 -0.397 -0.025 -0.451 0.463 -0.553 -0.808 -0.316 -0.534 0.051 0.177 -0.042 0.757 -1.423 -1.339 -0.457 -1.489 -0.360. -1.032 -0.081 0.087 0.776 1.271 2.221 1.162 -1.505 -0.482 2.213 -0.912 -1.569 -0.054 1.240 1.144 -0.078 -0.853 0.222 0.285 3.052 -0.508 -0.398 -0.927 0.343 -0.782 0.785 -1.120 -0.668 -0.581 0.233 0.641 0.483 -0.192 -1.063 0.061 0.097 -0.331 -0.321 -0.383 0.260 -0.580 -0.660 -0.496 -0.272 0.145 0.095 -0.217 0.642 -1.452 -1.134 -0.334 -1.511 -0.370.       . -1.052 0.419 -0.013 2.021 1.853 2.759 1.748 -1.956 -0.596 2.420 -1.580 -2.029 1.601 2.500 1.244 0.207 -0.907 0.130 0.416 3.130 -0.526 0.113 -0.822 0.645 -0.167 1.027 -0.740 -0.346 -0.457 0.052 0.423 0.468 -0.516 -1.251 0.422 0.231 -0.392 -0.337 -0.161 0.292 -0.830 -0.113 0.535 -0.108 0.302 0.575 0.289 0.278 -1.429 -1.245 -0.399 -0.864 0.367. 

(233)  !. 2.613 1.248 2.690 -0.463 0.281 0.251 0.032 1.192 -0.237 -0.287 0.986 2.216 -0.823 -0.514 0.543 -0.146 0.078 0.014 1.215 0.548 0.937 0.658 0.733 -0.635 -0.532 -0.521 1.217 0.356 0.535 1.156 0.422 0.719 1.052 1.905 1.118 0.382 1.378 0.818 0.548 1.229 1.337 0.128 -0.849 0.712 0.821 1.511 -0.188 1.089 1.401 0.378 0.479 0.844 -0.176. 2.459 1.695 2.631 -0.417 0.393 0.579 0.423 1.555 0.059 0.105 1.048 2.241 -0.767 -0.594 0.759 0.126 0.262 0.263 1.268 0.631 1.007 0.901 1.035 -0.618 -0.510 -0.374 1.517 0.322 0.763 1.352 0.778 0.719 0.986 1.937 0.775 0.710 1.607 0.961 0.662 1.185 1.308 0.260 -1.088 0.746 0.655 1.630 -0.092 1.011 1.187 0.367 0.580 0.847 -0.354. 1.993 1.233 2.562 -0.955 0.262 0.451 0.598 0.754 -0.266 -0.299 0.753 1.932 -1.481 -1.083 0.291 -0.643 -0.070 0.646 1.073 0.234 0.535 0.593 0.433 -0.677 -0.844 -0.320 0.606 0.115 0.499 1.153 0.613 0.249 1.195 1.525 0.688 0.290 1.473 0.970 0.274 0.654 1.072 -0.079 -1.334 0.260 0.695 0.993 -0.213 0.680 0.685 0.067 0.312 0.291 -0.643.

(234) -1.674 -0.748 0.001 -0.752 -1.379 -0.844 0.931 -0.783 0.821 -0.994 2.807 -0.039 -1.144 -2.358 0.793 -1.126 -0.845 -1.148 0.290 0.129 -0.934 3.185 -0.545 0.425 -0.039 -1.485 -1.489 4.355 -1.009 -0.973 1.497 -0.505 1.037 -0.754 -0.218 -1.425 -0.473 0.025 -0.469 -1.028 0.154 -0.973 0.718 -1.146 -1.564 1.011 -1.046 1.439 -0.502 -0.978 -0.814 -1.493 -1.312. -1.197 -0.204 -0.358 -1.037 -0.429 0.632 1.897 0.374 1.522 0.713 3.641 0.381 -0.355 -1.351 2.035 -0.639 0.374 0.646 1.232 0.386 -0.010 5.775 -0.366 -0.203 0.284 -1.063 -1.235 6.783 -0.201 0.314 1.828 -0.396 1.478 -0.853 0.430 -1.117 0.060 0.060 0.039 -0.319 0.116 -1.168 0.369 -1.360 -0.574 0.524 -1.382 2.452 0.332 -1.108 -0.859 -0.966 -1.063. -1.085 -0.392 -0.545 -0.775 -0.490 -0.153 1.657 0.577 0.948 0.597 3.341 0.313 -0.303 -1.162 0.828 -0.817 0.390 0.460 0.942 0.081 -0.666 5.310 -0.484 -0.223 0.231 -0.991 -1.254 4.087 -0.291 -0.537 1.588 -0.557 0.717 -0.727 0.250 -1.106 -0.168 0.018 -0.257 -0.577 0.121 -1.018 0.547 -1.043 -0.437 0.988 -1.321 2.111 0.432 -1.019 -0.935 -1.032 -0.926.       . -0.814 0.178 -0.551 -0.982 0.026 0.047 1.480 1.025 0.696 1.011 2.981 0.416 0.375 -1.545 1.080 -1.184 1.006 0.658 1.315 0.090 0.176 4.043 -0.369 -0.569 0.650 -1.053 -1.626 4.178 0.014 -0.768 1.714 -0.545 0.990 -0.957 0.295 -1.202 -0.178 0.002 0.227 -0.385 0.546 -0.779 0.766 -1.126 -0.101 0.444 -1.685 1.967 0.118 -1.131 -1.249 -0.571 -0.912. 

(235)  !. -0.251 0.570 0.675 1.156 -0.146 0.721 -1.457 -0.207 -0.613 -0.710 0.591 0.430 0.494 0.305 0.242 0.469 -0.806 0.143 0.021 0.748 0.492 0.327 0.433 0.001 -0.477 -0.420 -0.081 -0.831 -0.807 0.469 -0.645 0.638 0.565 -0.305 0.034 1.159 0.134 0.469 -0.335 0.290 -0.415 1.221 1.012 0.964 -0.257 1.657 1.658 0.067 0.123 1.775 1.513 0.489 -0.268. -0.013 0.783 0.903 1.196 0.203 0.884 -0.990 -0.267 -0.049 -0.423 0.603 0.684 0.557 0.689 0.314 0.681 -0.250 0.162 0.151 0.817 0.747 0.403 0.675 0.294 -0.504 -0.080 0.535 -0.393 -0.586 0.610 -0.491 0.842 0.526 -0.016 0.306 1.156 0.294 0.297 0.027 0.383 -0.426 1.441 1.028 0.935 -0.146 1.569 1.656 0.145 0.160 1.474 1.398 0.353 0.227. -0.509 0.476 0.514 0.822 -0.169 0.416 -0.875 -0.217 -0.195 -0.701 0.386 0.489 0.297 0.021 0.384 0.396 -0.658 -0.071 0.134 0.916 0.258 0.103 0.135 0.303 -0.945 -0.375 0.255 -0.370 -0.855 0.463 -0.314 0.421 0.224 -0.163 -0.044 0.557 0.070 0.029 -0.170 0.117 -0.614 0.785 1.035 0.385 -0.491 1.637 1.184 0.220 0.073 0.835 1.109 -0.150 -0.294.

(236) -0.852 -1.560 -0.847 -0.654 -1.212 -0.273 0.883 -1.800 0.449 4.020 0.507 0.790 1.704 1.497 0.647 1.184 0.046 -1.333 0.752 -0.207 3.281 0.167 1.563 -1.088 -0.437 -1.123 3.623 0.301 -1.360 -0.035 1.547 -0.446 0.269 0.774 0.242 -0.774 -0.085 -1.562 -0.489 -1.042 -0.997 0.996 0.123 -0.024 -0.549 -1.239 -0.628 1.085 0.117 0.594 -0.525 0.403 -1.725. -0.761 -1.179 -0.438 -0.355 -0.737 0.787 2.134 -1.501 1.803 4.281 0.910 2.047 4.103 1.753 1.981 3.069 1.053 -1.078 1.609 0.687 4.262 2.231 2.290 -1.209 0.644 -0.601 4.756 0.387 -1.081 1.304 2.260 0.377 0.008 1.122 0.091 -0.711 -0.078 -1.292 -0.276 -0.840 0.280 1.598 0.111 -0.695 -1.163 -1.181 -0.989 1.490 0.084 0.232 -0.769 0.904 -1.669. -0.881 -1.045 -0.353 -0.312 -0.801 0.559 1.346 -1.510 1.463 4.390 1.001 1.729 3.824 1.133 1.872 2.451 0.990 -0.936 1.658 0.560 3.967 1.062 1.485 -1.188 -0.108 -0.341 2.970 0.453 -1.101 1.233 2.285 0.458 -0.468 0.873 -0.149 -0.850 -0.300 -1.081 -0.409 -1.050 0.203 0.719 -0.020 -0.456 -1.155 -1.141 -0.899 1.015 -0.036 -0.207 -0.910 0.165 -1.310.       . -1.185 -0.996 0.082 0.361 -0.714 1.176 1.862 -1.970 1.456 3.927 1.361 1.706 3.252 1.061 1.026 2.097 1.695 -1.320 1.494 0.507 3.147 -0.018 1.516 -1.530 -0.223 -0.263 3.229 0.585 -1.198 0.691 2.114 0.467 -0.715 1.098 -0.540 -0.821 -0.475 -1.404 -0.222 -1.385 0.462 1.185 -0.075 -0.802 -1.630 -1.561 -1.460 0.896 -0.129 -0.408 -1.278 -0.166 -1.616. 

(237)  !. 0.626 0.581 -0.815 0.352 0.764 0.046 -0.704 0.924 -0.226 0.386 -0.292 0.322 0.209 1.879 -0.102 0.011 -0.358 0.493 0.562 0.838 0.541 1.110 0.960 1.106 0.618 0.174 -0.484 0.061 -0.051 0.510 1.489 -0.214 0.641 0.241 1.030 0.295 0.883 1.237 0.897 0.630 -0.068 1.234 0.973 1.608 3.032 1.638 2.186 1.117 1.695 1.697 1.539 0.715 0.726. 0.765 0.637 -0.578 0.184 0.807 0.164 -0.241 1.412 -0.103 0.479 -0.166 0.324 0.221 1.608 0.123 0.147 -0.349 0.581 0.696 1.046 0.802 1.256 1.343 1.307 0.902 0.377 -0.171 0.543 0.206 0.463 1.556 0.361 0.819 0.696 1.419 0.365 1.068 1.453 0.929 0.752 0.225 1.209 1.283 1.838 3.221 2.100 2.010 0.958 1.743 1.709 1.591 0.556 0.908. 0.602 0.282 -1.035 -0.210 0.279 -0.044 -0.587 0.518 -0.124 0.738 -0.508 0.613 0.491 1.875 0.104 0.195 -0.635 0.367 0.379 0.827 1.182 1.024 1.403 0.975 0.491 0.190 0.370 0.188 -0.109 0.481 1.237 0.083 0.729 0.258 1.014 0.223 0.734 0.978 0.598 0.492 -0.045 0.904 0.744 1.238 2.504 1.618 1.922 0.890 1.261 2.154 1.174 0.504 0.260.

(238) -1.135 -0.608 -1.216 -0.023 -0.671 0.179 0.386 0.419 -0.370 1.042 0.733 0.388 1.020 1.769 -0.804 -0.622 1.959 -0.491 0.450 0.710 0.956 0.755 0.879 0.749 0.649 1.907 0.266 -0.541 0.855 -0.006 0.912 1.268 1.312 1.222 -0.337 0.081 -0.527 0.161 -0.422 1.149 0.091 0.565 0.300 1.551 1.312 0.156 -0.183 0.422 -0.289 0.039 -0.483 -0.766 0.652. -0.913 -0.713 -0.978 0.087 0.028 -0.087 1.657 -0.147 1.328 0.836 1.459 1.692 0.525 2.495 -0.381 -0.220 3.655 -0.153 1.753 3.357 1.623 0.805 0.913 0.941 0.807 2.406 -0.164 -0.292 1.157 -0.145 0.794 3.072 1.412 1.292 -0.292 -0.199 -0.344 0.652 -0.458 5.138 0.065 1.051 0.640 2.826 2.888 0.326 -0.156 -0.569 -0.621 -0.523 -0.374 -0.278 0.641. -0.656 -0.639 -0.857 -0.290 0.046 -0.022 1.630 0.047 1.362 1.273 2.001 2.357 0.973 3.466 -0.303 -0.104 3.747 -0.173 1.437 4.550 2.206 0.990 1.448 1.441 0.586 2.513 0.013 -0.151 1.395 0.126 0.908 1.732 1.942 1.546 -0.259 -0.265 -0.244 1.300 -0.391 6.477 0.423 1.134 0.932 4.051 3.583 0.158 -0.197 -0.510 -0.707 -0.417 -0.205 -0.084 0.635.       . -0.539 1.588 -1.437 -0.982 0.224 -0.117 0.188 0.070 -1.657 1.620 0.001 0.527 0.140 2.125 -1.966 -0.556 2.693 0.159 0.465 0.440 1.783 1.000 1.892 1.381 0.387 1.979 -0.303 0.167 0.571 -0.064 0.657 2.293 1.869 1.616 -0.351 0.133 -0.986 0.834 -0.432 3.806 0.459 0.926 0.425 2.369 1.709 0.040 0.098 -0.032 -0.364 -0.491 -0.882 -0.605 0.185. 

(239)  !. 0.832 -0.594 -0.588 1.100 1.413 0.663 -1.534 -0.268 2.196 0.457 -0.309 -0.352 1.204 -0.136 0.900 -0.419 -0.047 0.177 0.872 4.994 -0.205 0.775 -0.422 -0.101 -0.409 -0.226 0.705 1.119 -0.647 3.634 0.433 -0.935 -0.136 -0.934 -0.276 1.519 -1.405 0.128 0.770 2.459 0.222 -0.002 1.613 -1.476 -1.264 -0.895 0.312 2.635 0.973 5.973 0.793 1.380 1.236. 0.909 -0.505 -0.026 1.542 1.589 0.899 -1.011 -0.318 1.967 0.669 0.032 -0.491 1.114 -0.046 0.943 -0.613 0.132 0.202 0.508 4.898 -0.139 0.901 -0.344 0.079 -0.208 -0.120 0.679 1.017 -0.345 3.168 0.440 -0.579 -0.019 -0.395 -0.178 1.553 -1.209 0.304 0.641 2.043 0.193 -0.004 1.514 -1.165 -0.913 -0.558 0.577 2.817 0.735 5.250 0.725 1.014 1.190. 0.514 -1.084 -0.469 1.297 0.947 0.568 -0.501 0.766 2.334 0.665 1.423 0.578 2.589 1.557 1.998 -0.512 0.765 0.986 1.590 7.602 1.750 2.013 0.212 0.073 0.498 0.006 1.113 0.823 0.812 3.287 1.490 0.058 0.912 -0.195 -0.016 1.188 -0.751 0.681 0.606 1.796 0.142 1.080 1.759 -1.354 -0.358 -0.203 0.754 3.344 0.422 4.353 1.350 1.455 2.209.

(240) -0.112 0.002 0.200 -0.484 -0.421 0.120 -0.350 0.465 0.653 -0.754 -0.655. -0.126 -0.392 0.313 -0.709 -0.086 -0.278 -0.734 0.140 0.208 -0.452 -0.410. -0.056 -0.343 0.414 -0.925 0.254 0.111 -0.772 0.466 0.186 -0.235 -0.280.       . 0.130 0.127 0.515 -0.404 -0.091 0.029 -0.426 0.248 -0.114 -0.671 -0.384. 

(241)   !. 0.281 -0.448 -0.320 1.818 -0.644 1.193 4.046 0.918 -0.850 -0.044 0.072. 0.340 0.031 -0.101 1.811 -0.431 1.017 2.530 0.957 -0.739 0.039 0.098. 1.305 0.735 0.515 1.854 -0.518 1.299 1.830 1.581 -0.450 0.369 1.428.

(242) TF Number TF mode TF mode of Vesicles Area (volume Area (mean (masked) weighted) int. weighted) 0.708 1.157 1.098 0.488 -1.365 -0.936 0.204 -1.259 -1.215 0.191 -0.164 0.319 0.894 1.523 0.874 -0.479 -0.137 1.563 1.363 -1.526 -0.389 -0.086 -1.612 -0.601 -0.410 -1.486 -0.365 -0.338 0.410 0.873 -0.125 -1.352 0.689 -0.993 -2.068 -1.899 -1.197 -0.512 0.769 -1.036 -1.634 -0.244 -1.679 -0.782 -1.205 -0.115 -2.328 -0.879 0.354 -2.808 -1.188 0.029 -1.253 -2.035 -1.004 -0.417 0.839 0.687 -2.540 -2.254 0.717 -0.839 -0.706 -1.009 1.688 3.476 -1.580 0.298 0.919 -1.514 4.451 4.458 -0.778 0.804 1.106 -0.990 -1.249 1.602 -1.745 -0.534 -0.588 -0.343 -0.534 -1.295 -4.425 1.264 -0.380 -0.230 -0.304 -0.313 -0.678 0.863 0.161 -2.132 0.870 2.585 -0.347 -0.348 -1.701 -1.637 0.580 0.979 -1.281 0.944 -0.111 -0.655 1.064 2.288 -0.284 -1.207 -2.983 -0.632 1.898 2.477 -0.488 0.717 1.560 0.211 -1.535 -0.219 0.266 0.235 0.803 -1.803 0.821 1.442 -2.753 -1.716 0.514 0.140 -1.913 0.272 1.144 -3.159 -1.310 1.019 -1.268 0.245.       . TF mode Area 0.812 -1.132 -1.469 0.371 0.930 0.447 -0.841 -0.325 -0.628 1.031 -0.012 -0.733 0.849 -0.366 0.427 -0.960 -1.302 -1.457 0.170 -1.551 -0.709 2.492 1.458 3.960 1.744 1.357 0.258 -0.712 1.502 0.448 0.397 1.405 -0.855 -0.132 0.175 0.519 -1.424 2.717 2.010 -0.921 0.909 2.040 0.978 -0.818 -0.885 -0.330. TF mode Mean intensity (volume weighted) -0.108 -0.004 0.662 0.132 1.675 1.922 1.381 2.889 4.073 2.931 1.618 0.586 -0.041 1.982 -0.527 0.916 1.383 1.507 4.485 0.308 -0.140 1.089 -0.537 -0.111 0.005 -0.868 0.043 -0.253 1.570 0.453 0.725 0.060 -0.343 -1.074 -1.421 -0.323 0.556 -0.499 -0.005 0.741 6.225 1.617 1.862 1.800 3.265 1.281. 

(243) ! !. TF mode Mean intensity (mean int. weighted) -0.402 0.000 0.736 0.201 1.827 1.821 1.160 3.306 4.083 3.082 1.776 0.964 0.254 2.180 -0.417 0.923 1.714 1.839 5.314 0.661 -0.189 1.313 -0.403 -0.295 0.370 -0.886 0.488 -0.228 2.124 0.586 0.547 0.006 -0.583 -0.997 -1.403 -0.713 1.016 -0.352 -0.087 0.804 5.924 1.802 2.214 2.096 3.544 1.506. TF mode Mean intensity 1.917 0.000 0.501 0.108 1.132 0.898 1.505 0.835 0.201 0.792 1.903 -0.022 -0.728 0.300 -1.563 0.180 0.794 -0.227 0.896 -0.016 -0.028 0.972 -1.256 -0.215 -1.151 -0.612 -0.978 -0.671 -1.963 0.015 0.661 -1.279 -1.235 -1.040 -1.291 0.405 -0.308 -0.062 -0.225 -0.138 0.778 1.424 0.059 -0.023 0.983 1.150.

(244) 0.113 0.618 -0.389 1.317 -0.632 1.389 0.164 0.824 0.626 0.948 -1.597 0.875 -0.184 1.864 0.319 0.942 1.299 -0.216 0.175 1.237 0.920 0.082 -1.714 0.122 -0.529 -1.438 0.425 -0.012 0.183 -0.081 -1.467 0.371 0.079 0.153 0.671 1.009 -0.133 -0.733 0.201 -1.096 -0.026 0.189 -0.332 -0.803 0.283 -0.886 -0.856 -1.782 -0.069 -1.977 -1.095 -2.810 -1.571. 1.064 -0.624 1.873 0.153 -0.478 -0.411 -1.037 -0.453 -0.500 0.234 7.205 0.222 -0.298 -1.326 -0.028 -1.406 -0.205 -1.203 -0.013 0.489 -0.580 -0.659 -2.679 -0.645 -0.605 -1.532 -2.059 0.123 -0.948 0.514 2.072 0.288 -1.153 -0.950 0.392 -0.263 0.128 2.153 1.381 1.257 -0.353 -0.348 0.027 0.389 0.315 3.159 1.740 2.846 2.098 1.773 -0.825 1.180 -0.484. -1.007 1.250 1.697 0.801 -0.599 -0.364 -0.908 -0.532 -0.502 0.212 6.441 0.728 -0.180 -0.597 0.409 -1.554 -0.176 -1.240 0.513 0.507 -0.868 -1.054 -2.687 -1.154 -1.115 -1.733 -1.901 -0.189 -1.442 0.393 1.527 -0.039 -1.121 -1.787 0.116 -0.848 0.050 1.617 0.851 0.528 -1.542 -1.020 -1.196 -0.995 -0.134 2.896 1.211 1.278 1.389 -0.777 -1.783 -0.490 -0.709.       . -0.450 0.747 1.280 0.322 -0.185 -1.145 -0.766 -0.537 -1.296 -0.118 6.067 -0.146 0.433 -1.473 0.097 -2.119 -0.580 -0.306 0.392 -0.147 -1.326 -0.809 -0.793 -1.348 -0.097 -0.513 -2.301 -0.436 -1.378 0.289 2.252 -0.184 -0.747 -1.217 -0.036 -1.645 0.166 0.387 1.210 1.822 -1.672 -1.023 -0.679 0.250 -0.169 4.197 1.992 2.792 1.340 1.123 -0.062 0.734 1.191. 

(245) " !. 1.228 1.246 1.830 1.237 -1.019 0.926 -0.883 0.273 0.594 1.291 0.158 1.670 -0.853 1.573 0.403 0.693 1.034 -1.258 0.433 1.835 0.312 -0.676 -2.581 -0.574 -1.408 -1.900 0.753 -0.121 -0.450 0.189 -1.363 0.171 -1.089 -0.879 0.335 0.877 -0.258 0.594 -0.474 -1.192 0.499 -0.960 -0.635 -1.326 0.177 -0.927 -0.101 -2.053 0.180 -2.401 -2.363 -2.524 -1.956. 1.299 1.269 1.794 1.448 -1.246 0.913 -0.918 0.155 0.582 1.315 -0.415 1.746 -0.800 1.912 0.443 0.645 0.978 -1.373 0.519 2.062 0.375 -0.730 -2.705 -0.614 -1.572 -1.997 0.857 -0.236 -0.499 0.226 -1.528 0.124 -1.132 -0.961 0.351 0.924 -0.314 -0.092 -0.561 -1.290 0.591 -1.004 -0.897 -1.363 0.132 -0.944 -0.007 -2.248 0.119 -2.655 -2.489 -2.694 -2.060. 1.195 1.697 0.744 1.362 -1.482 1.054 -1.070 0.096 0.792 1.140 -1.385 1.570 -0.969 2.105 0.155 0.722 1.030 -1.729 0.288 2.245 0.466 -0.909 -3.035 -0.812 -1.693 -2.274 0.701 -0.263 -0.512 0.307 -1.826 0.094 -1.273 -0.948 0.451 1.344 -0.355 -0.470 -0.411 -1.341 0.609 -0.989 -0.948 -1.451 0.028 -1.047 -0.122 -2.640 0.353 -3.001 -2.693 -3.144 -2.278.

(246) -2.285 -1.502 -2.222 0.669 1.041 1.140 0.841 -0.876 0.645 1.393 0.426 -1.315 -0.768 0.235 0.518 0.418 -1.471 0.136 -0.215 1.214 -0.375 -1.083 -1.367 -0.187 -1.467 -0.057 -2.773 -0.893 -0.597 -0.508 -0.605 0.690 -0.349 -0.765 0.058 -0.622 -0.596 -0.264 -0.296 -1.183 -1.434 -1.105 -0.212 -1.768 -0.167 -0.501 -0.673 -0.460 -1.520 -1.258 -0.131 -4.968 -0.718. 4.850 1.447 1.878 0.111 0.172 0.580 -0.291 -1.179 -1.057 -1.333 -1.013 5.146 0.215 -0.693 -1.331 -0.606 -1.600 -0.211 -1.217 -0.697 -1.181 1.261 -1.173 -1.177 -1.450 -0.462 -1.472 -1.346 -1.241 -1.471 0.555 -1.095 -2.462 -0.676 -1.094 -0.266 -0.640 -0.195 -0.627 1.105 -0.210 0.207 -1.341 -1.383 -0.200 1.779 0.900 -0.344 -0.183 -1.161 1.486 -4.763 -0.204. 4.695 1.216 1.071 0.068 -0.102 0.753 -0.555 -1.647 -1.138 -1.515 -1.075 2.793 -0.210 -0.496 -1.360 -0.711 -2.184 -0.130 -1.418 -0.345 -0.975 0.591 -1.828 -1.419 -1.744 -1.086 -3.176 -1.728 -1.832 -1.779 1.027 -1.321 -3.442 -1.515 -1.508 -0.726 -1.322 -1.192 -1.116 0.695 -0.897 -0.484 -1.679 -1.909 -0.619 0.976 0.436 -0.003 -1.186 -1.856 0.848 -5.572 -0.883.       . 7.574 3.108 3.513 -0.086 -0.801 0.592 -0.469 -0.166 -0.735 -2.177 -0.513 1.661 0.900 -0.019 -1.007 -0.574 -0.585 -0.162 -0.560 -1.029 -0.581 0.804 -0.110 -1.059 0.161 -0.738 -1.670 -0.341 -0.824 -1.261 0.634 -1.838 -3.113 -0.147 -1.584 -0.573 -0.474 -0.347 -0.405 2.183 0.301 1.158 -0.754 -0.417 0.398 1.561 1.979 0.107 1.008 -0.340 1.387 -2.100 0.358. 

(247) # !. -1.764 -1.410 -1.753 -0.158 1.329 1.403 0.787 -2.141 -0.022 1.280 -0.319 0.688 -1.330 -0.280 0.024 -0.283 -1.820 0.236 -0.741 1.106 -0.757 -0.437 -1.885 -0.966 -2.305 -0.891 -2.143 -1.868 -1.801 -1.265 0.720 0.383 -1.124 -1.281 -0.688 -0.744 -1.032 -1.013 -1.257 -0.826 -1.495 -2.050 -1.912 -2.163 -1.315 -0.791 -1.119 0.767 -2.068 -2.044 -1.053 -3.570 -1.647. -1.975 -1.472 -1.819 -0.327 1.375 1.337 0.503 -2.159 0.295 1.226 -0.255 -1.231 -1.461 -0.409 0.160 -0.353 -1.942 0.272 -0.710 1.051 -0.712 -0.685 -1.947 -1.019 -2.377 -1.028 -2.557 -1.934 -1.915 -1.332 0.606 0.300 -1.249 -1.220 -0.754 -0.853 -1.094 -0.964 -1.359 -0.930 -1.528 -2.219 -2.073 -2.232 -1.357 -0.899 -1.174 0.473 -2.138 -2.085 -1.205 -3.746 -1.728. -2.283 -1.695 -2.093 -0.488 1.590 1.327 0.416 -2.430 0.056 1.514 -0.410 -2.039 -1.643 -0.468 -0.146 -0.516 -2.319 0.048 -0.913 1.147 -0.967 -1.037 -2.169 -1.129 -2.701 -1.226 -3.118 -2.157 -2.097 -1.496 0.507 0.259 -1.459 -1.420 -0.766 -0.958 -1.258 -1.027 -1.409 -1.157 -1.600 -2.473 -2.196 -2.497 -1.378 -1.114 -1.147 0.442 -2.408 -2.199 -1.264 -4.461 -1.812.

(248) -2.078 -0.671 -1.136 -1.379 -0.859 -0.891 -0.239 0.729 0.873 -1.022 1.575 -0.450 -0.072 -2.114 0.876 -0.686 -0.570 -0.608 0.025 0.188 -1.123 0.965 0.251 -0.152 0.352 -1.436 -1.186 1.385 0.218 -1.603 0.438 -0.766 0.552 -0.466 0.073 -1.436 -0.118 0.539 -0.432 -1.365 -0.419 -2.009 -0.414 -1.268 -1.735 -0.517 -2.107 0.511 -0.563 -0.718 -0.093 -1.623 -1.855. -1.395 -0.138 -0.145 0.460 -1.619 0.055 0.035 -0.513 -0.372 -1.594 -0.911 -0.303 -0.861 -1.382 -0.749 -0.840 -1.159 -1.456 -0.886 -1.753 -0.084 -0.103 -1.391 -1.380 0.056 -0.791 -1.718 0.115 -1.160 -0.871 -0.819 0.029 0.277 -1.047 -0.981 -0.582 -1.388 -1.027 0.136 0.612 1.321 1.583 1.168 0.264 -0.573 -0.949 4.090 0.469 0.583 2.101 -1.221 2.246 -1.834. -1.967 -0.369 -0.811 -0.105 -1.821 -0.170 0.358 -0.201 -0.735 -1.604 -0.921 -0.634 -0.626 -1.834 -1.119 -1.373 -0.556 -1.292 -0.872 -2.054 -0.164 0.112 -1.534 -1.831 -0.571 -1.094 -1.763 -0.742 -1.793 -1.305 -1.274 0.012 -0.550 -1.721 -1.318 -1.241 -1.807 -1.543 -0.124 0.311 0.772 1.399 0.494 -0.320 -1.047 -1.253 2.530 -0.086 0.206 1.650 -1.695 0.769 -1.859.       . 0.118 0.899 0.212 1.621 -0.246 0.672 0.147 -0.306 -1.107 0.326 -1.527 0.437 0.250 0.633 -1.653 -0.226 0.016 -0.399 -0.484 -1.566 1.324 -0.455 -1.472 -1.199 -1.333 0.188 -0.883 -1.728 -1.490 -0.144 -1.117 1.121 -0.786 -1.277 -1.033 0.153 -1.263 -1.913 0.829 2.069 1.473 4.264 1.122 1.034 0.541 -1.075 3.120 -0.062 1.787 3.287 -1.595 4.104 -0.590. 

(249) $ !. -2.537 -1.590 -0.944 -1.497 -1.399 -1.264 0.981 -0.141 0.842 -1.817 2.435 -0.791 -1.080 -2.578 0.800 -1.327 -1.235 -1.410 -0.781 -0.788 -1.507 1.067 0.000 -0.232 0.821 -2.067 -1.666 3.483 -0.986 -1.339 -0.177 -0.766 0.762 -0.688 -0.371 -2.047 -1.004 0.023 -1.390 -1.762 -0.196 -1.918 -0.907 -1.682 -1.941 -0.920 -1.104 0.738 -1.252 -0.820 -0.714 -2.053 -1.851. -2.603 -1.577 -0.898 -1.539 -1.364 -1.343 0.897 -0.311 0.844 -1.834 2.644 -0.923 -1.204 -2.726 0.809 -1.473 -1.333 -1.529 -0.788 -0.760 -1.554 1.318 0.099 -0.363 0.968 -2.161 -1.683 3.582 -1.027 -1.382 -0.151 -0.736 0.834 -0.630 -0.292 -2.133 -1.023 0.005 -1.553 -1.891 -0.216 -1.979 -0.910 -1.839 -2.056 -0.955 -1.750 0.961 -1.343 -1.125 -0.767 -2.140 -1.906. -2.946 -1.707 -0.914 -1.654 -1.594 -1.521 0.739 -0.413 0.988 -2.067 2.590 -1.264 -1.375 -3.084 0.875 -1.761 -1.553 -1.746 -0.870 -0.913 -1.649 1.403 0.098 -0.381 0.979 -2.426 -1.913 3.881 -1.128 -1.540 0.012 -0.877 0.871 -0.808 -0.382 -2.348 -1.113 0.128 -1.642 -2.187 -0.460 -2.236 -0.805 -1.861 -2.315 -1.020 -2.281 0.948 -1.545 -1.369 -0.733 -2.374 -2.045.

(250) -1.575 -0.854 0.200 -1.008 -1.565 0.493 0.863 -1.292 0.506 1.706 1.248 0.424 0.989 1.288 -0.165 0.805 0.926 -0.191 1.008 -0.313 1.106 -1.029 -0.460 -0.463 -0.051 0.006 1.331 0.188 -0.028 0.143 0.688 -0.625 -0.875 -0.017 0.432 -1.145 0.302 -0.955 -0.558 -0.488 -0.709 -0.252 -1.221 -1.692 -1.032 -1.212 -1.954 0.657 -0.023 -0.921 -0.325 0.465 -1.356. -0.345 -0.420 -0.991 -0.055 0.353 -0.742 0.201 -0.640 -1.120 -0.617 -1.271 -0.055 -0.557 -0.421 -0.422 -0.518 -0.650 -1.544 -0.325 -1.604 -0.430 0.039 0.198 -1.273 -1.549 -1.698 -1.646 -0.371 -1.720 0.133 0.385 -1.123 0.067 0.463 -1.320 2.154 -1.031 -1.239 0.663 -0.541 0.301 1.209 1.092 2.180 1.071 -0.223 -0.165 -0.317 0.038 0.196 -0.620 -0.759 1.030. -1.295 -1.488 -1.380 -0.976 0.068 -0.653 0.737 -1.233 -1.146 -0.289 -1.366 -0.066 0.062 -0.650 -0.488 -0.312 -0.729 -2.005 0.044 -1.566 0.300 0.409 0.403 -1.703 -1.981 -2.220 -1.863 -1.253 -2.133 -0.262 0.375 -1.295 -0.133 -0.132 -1.832 0.886 -1.324 -1.822 -0.014 -0.963 -0.572 0.610 0.838 1.639 -0.107 -1.083 -1.371 -0.272 -0.420 -0.065 -0.968 -1.408 0.188.       . 0.884 -0.629 -0.995 -0.042 2.194 -0.825 0.063 0.984 -1.295 -1.352 -1.551 -0.407 -0.323 -1.089 -0.281 -0.556 -0.848 -1.721 -0.565 -1.181 -0.701 1.027 -0.232 -0.516 -1.603 -1.433 -2.671 -1.236 -1.496 0.318 0.022 -0.662 0.667 -0.075 -1.797 -0.033 -0.947 -0.935 1.393 0.058 0.329 1.211 2.668 3.413 1.580 0.951 0.732 -1.031 1.153 0.815 -0.758 -1.134 2.716. 

(251) % !. -2.117 -1.916 -0.989 -1.340 -1.853 0.316 1.302 -2.100 0.145 1.796 1.116 0.625 0.976 1.538 0.467 1.700 0.366 -0.956 1.173 -0.582 3.337 -0.687 1.149 -1.259 -0.662 -1.373 2.879 -0.225 -1.494 -0.242 1.394 -1.214 -0.758 0.977 -0.359 -0.656 -0.283 -1.853 -0.989 -1.553 -1.757 0.084 -0.986 -1.272 -1.325 -2.104 -2.382 1.204 -1.015 -0.812 -0.909 0.434 -2.079. -2.140 -2.033 -1.069 -1.538 -1.906 0.222 1.311 -2.168 0.230 1.835 1.289 0.673 1.194 1.871 0.457 2.206 0.265 -0.970 1.262 -0.609 3.692 -0.708 1.146 -1.308 -0.682 -1.501 3.086 -0.302 -1.566 -0.250 1.704 -1.250 -0.765 0.886 -0.396 -1.392 -0.286 -1.986 -1.071 -1.497 -2.062 0.254 -0.989 -1.223 -1.311 -2.218 -2.420 1.279 -1.094 -0.812 -1.024 0.393 -2.119. -2.403 -2.319 -1.064 -1.723 -2.120 0.230 1.172 -2.368 0.350 2.126 1.440 0.709 1.092 1.922 0.360 1.806 0.234 -1.097 1.226 -0.965 3.667 -0.967 1.251 -1.342 -0.713 -1.591 3.534 -0.279 -1.727 -0.191 1.778 -1.314 -0.743 0.780 -0.389 -1.821 -0.440 -2.126 -1.143 -1.719 -2.233 0.156 -1.098 -1.407 -1.374 -2.432 -2.668 1.345 -1.026 -0.777 -1.111 0.546 -2.337.

(252) -0.210 -1.355 -0.798 -0.345 -1.560 -0.925 -1.293 0.549 -2.234 -0.279 0.961 -0.223 -0.133 -1.294 -0.608 -2.751 1.587 -2.041 -0.904 0.264 -1.379 -0.663 0.149 -1.782 0.277 0.415 0.810 -0.171 0.261 0.629 1.348 0.128 0.044 -0.109 0.233 -0.792 -1.687 0.104 0.005 -0.730 1.262 0.703 0.121 -0.781 1.014 -0.845 0.236 -1.251 -2.127 -1.096 -0.161 -0.013 -0.679. -0.966 -1.561 -1.463 -0.702 0.842 0.459 0.184 -0.379 -2.261 -0.403 -2.174 -1.709 -1.830 -1.358 0.347 -1.221 -2.134 -0.488 -1.212 -3.656 -1.819 -1.967 -1.161 -0.773 -1.180 0.133 -3.374 -0.881 -3.550 -2.796 -1.472 -1.123 -0.923 -0.517 -0.385 1.588 -1.813 -1.399 -0.586 -0.874 -2.427 -1.613 -0.180 1.590 0.425 -0.187 -0.261 0.867 1.653 -2.635 -2.225 -1.266 -0.970. -1.590 -1.962 -1.819 -1.137 -0.116 0.329 1.822 -2.545 -3.521 -0.282 -1.487 -0.854 -1.866 0.668 0.010 -1.368 -1.524 -0.710 -0.550 -1.334 -1.906 -1.455 -0.271 -0.012 -1.835 0.626 -3.655 -1.402 -3.974 -2.852 -1.355 -1.132 0.753 -0.480 -0.947 0.552 -1.241 1.194 -0.491 -2.168 -1.556 -0.924 0.313 1.046 0.466 -0.218 -0.291 1.264 1.159 -1.752 -2.685 -0.902 -0.620.       . -1.382 -0.217 -0.372 -0.919 1.344 1.190 2.130 -1.324 -0.615 -0.238 -2.172 -0.605 -1.331 0.787 1.484 -0.439 -1.221 0.315 -0.241 -1.538 -0.945 -0.920 -0.360 -0.595 -1.454 -0.359 -2.455 -0.966 -2.622 -1.830 -1.060 -1.372 0.210 -0.092 -0.130 0.434 0.181 0.807 -0.433 -0.972 -1.733 -1.351 -0.578 0.838 0.328 0.269 -0.414 1.143 1.252 -1.608 -1.328 -0.234 -0.585. 

(253)  !. -1.170 -2.478 -1.681 -0.559 -1.637 -0.942 2.054 1.719 1.833 0.687 1.893 3.171 1.685 3.345 1.111 1.061 1.612 0.969 1.814 0.615 1.327 2.880 2.472 2.138 0.855 1.033 1.011 0.099 -0.588 0.331 -0.876 -0.035 1.159 -0.765 -0.313 1.164 -0.086 1.008 -0.219 -0.791 1.591 0.159 1.746 2.628 2.709 -0.629 1.131 -0.815 0.357 0.169 0.741 -0.392 -0.382. -1.323 -2.575 -1.717 -0.594 -1.756 -0.975 2.661 2.050 3.134 1.048 1.867 3.399 1.860 3.979 1.700 1.706 1.828 1.360 2.202 1.025 1.640 3.322 2.259 2.507 1.154 0.665 1.373 0.134 -0.276 0.625 -0.739 0.729 1.288 -0.604 -0.741 0.979 0.202 1.056 0.004 -0.809 1.354 0.129 1.759 2.730 2.652 -0.516 1.202 -0.909 0.450 0.403 0.700 -0.472 -0.545. -1.459 -2.854 -1.862 -0.514 -1.992 -0.960 0.122 0.111 -0.796 1.294 0.752 0.316 0.544 1.054 -0.987 -0.947 2.250 -0.803 0.357 0.687 1.071 1.086 1.046 0.272 1.173 1.436 0.584 -0.637 1.182 -0.207 1.363 0.229 0.998 0.807 -0.091 0.381 -0.779 1.159 -0.117 -0.928 0.906 0.956 0.360 0.930 1.400 -0.162 0.330 -0.265 -0.700 -0.715 -0.455 -0.303 0.242.

(254) -0.892 -0.693 0.622 -1.943 -2.010 0.359 -1.948 -0.916 -1.818 -0.456 -1.000. 0.825 -0.948 -1.070 1.085 -1.464 -0.763 2.034 2.605 -2.255 -1.780 -2.407. 0.147 -0.206 -0.855 -0.216 -2.009 -0.630 1.112 2.384 -2.333 -1.176 -1.546.       . 0.235 0.623 -1.441 0.992 -0.088 -1.026 1.234 1.322 -1.807 -0.507 -0.371. 

(255)  !. 0.414 1.418 1.420 -1.292 0.103 -0.280 0.733 -0.678 1.465 0.613 -0.116. 0.432 1.488 1.426 -1.443 0.180 -0.241 0.725 -0.915 1.670 0.831 0.103. -0.156 -0.428 0.701 -1.492 -1.033 -0.185 -0.287 0.077 -0.302 -0.440 -0.580.

(256) TF mode Integral intensity (volume weighted) 1.782 0.476 0.823 0.426 0.564 0.966 1.062 0.912 1.339 1.919 0.983 -1.192 -0.511 0.550 -1.125 0.250 0.714 0.989 2.920 -0.310 -0.458 0.866 -1.375 -0.312 -1.029 -0.994 -0.885 -0.017 2.465 -0.382 -0.220 -0.632 -0.797 -0.197 -1.093 0.153 -0.329 -0.851 -0.392 1.018 2.948 1.459 -0.178 1.146 0.708 0.239. TF mode Integral intensity (mean int. weighted) 1.460 0.248 0.638 0.366 1.022 1.155 1.204 1.912 1.706 2.158 1.437 -0.759 -0.804 1.965 -1.150 0.518 1.055 0.870 4.640 -0.053 -0.611 0.860 -1.365 -0.116 -1.394 -0.970 -1.131 -0.590 3.092 0.194 -0.229 -0.779 -1.085 -0.663 -1.420 -0.044 -0.336 -0.971 -0.501 1.256 3.643 2.245 0.152 1.071 1.495 0.964. TF mode Integral intensity 2.096 -0.283 0.363 -0.091 1.188 0.892 1.168 0.776 0.132 0.913 1.818 -0.130 -0.752 0.347 -1.645 -0.160 0.471 -0.488 0.956 -0.330 -0.308 1.202 -1.262 0.082 -1.133 -0.609 -1.104 -0.867 -1.875 -0.005 0.525 -1.320 -1.542 -1.182 -1.467 0.216 -0.442 0.111 -0.198 -0.440 0.951 1.738 0.214 -0.255 0.777 0.994.       . TF Dist. to TF Dist. to nuc. (volume nuc. (mean TF Dist. to weighted | int. weighted nuc. (nuc. nuc. size | nuc. size size TF/EGF conormalized) normalized) normalized) localization 1.506 1.232 0.418 -3.661 -0.499 -0.519 -0.467 0.642 -0.057 -0.191 0.306 2.164 0.350 0.608 1.875 0.732 1.027 0.951 1.267 1.311 0.186 0.137 -0.027 -0.100 1.732 1.963 2.318 -0.112 0.357 0.244 0.878 1.026 -0.377 -0.026 0.389 2.986 0.500 0.850 2.715 2.846 0.306 0.571 1.637 -0.388 -0.039 0.213 0.557 1.278 0.299 0.560 0.588 -0.876 -0.604 -0.595 0.213 2.834 0.699 0.863 0.924 -1.968 -0.708 -0.679 -0.136 -0.699 1.383 1.424 1.851 0.803 1.357 1.622 2.274 0.367 0.675 0.875 1.375 0.442 -0.585 -0.660 -0.301 -0.548 0.123 0.099 0.670 -0.026 -0.525 -0.507 -0.425 0.880 2.167 2.513 2.808 -1.584 1.502 1.555 1.578 -1.917 1.150 1.391 4.025 -0.943 0.884 0.887 2.146 -0.256 0.604 0.511 2.415 -1.139 0.710 0.596 0.348 -1.712 -0.827 -0.294 1.474 1.807 1.958 1.896 3.508 -1.065 2.063 2.077 4.029 1.090 1.478 1.450 0.757 -1.020 1.444 1.698 1.586 -2.066 0.001 -0.167 -1.106 -1.720 0.341 0.514 -0.242 -2.527 0.953 0.874 1.796 -0.611 0.593 0.741 0.431 -0.476 0.802 0.960 1.461 -0.277 1.194 1.479 2.821 -1.671 0.265 0.048 -0.546 -1.248 -0.927 -0.574 0.680 5.218 -1.106 -1.216 -0.390 0.927 -0.974 -1.077 -1.291 -0.281 -1.044 -0.996 -0.155 1.129 0.417 0.530 2.582 3.291 0.575 0.570 1.805 1.359. 

(257)  !.

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