From 6121db4f6b15760d9bf8d50c203a0ba347661b94 Mon Sep 17 00:00:00 2001 From: Natalia Florekova Date: Sat, 21 Sep 2024 20:22:38 +0200 Subject: [PATCH 1/6] Added model 233 - breast cancer signalling pathways T47D complete --- .../README.md | 37 ++ .../metadata.json | 17 + .../model.aeon | 369 ++++++++++++++++++ .../model.bnet | 110 ++++++ .../model.sbml | 1 + models/summary.csv | 3 + report/.~lock.online_only_table_1.xlsx# | 1 + report/online_only_table_1.xlsx | Bin 56661 -> 58432 bytes .../citation.bib | 8 + .../metadata.json | 7 + .../notes.md | 11 + .../source.bnet | 110 ++++++ 12 files changed, 674 insertions(+) create mode 100644 models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/README.md create mode 100644 models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/metadata.json create mode 100644 models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.aeon create mode 100644 models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.bnet create mode 100644 models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.sbml create mode 100644 report/.~lock.online_only_table_1.xlsx# create mode 100644 sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/citation.bib create mode 100644 sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/metadata.json create mode 100644 sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/notes.md create mode 100644 sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/source.bnet diff --git a/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/README.md b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/README.md new file mode 100644 index 0000000..e00efe3 --- /dev/null +++ b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/README.md @@ -0,0 +1,37 @@ +# \[233\] BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE + + - Variables: 109 + - Inputs: 8 + - Regulations: 260 + - Publication: https://doi.org/10.1371/journal.pone.0298788 + - Source: https://github.com/Ktaoma/BoolSyn + - Keywords: source (?), curated (?), repaired (?), multi-valued (?) + + +### Modifications + +Removed regulations: +WNT1, WNT1 +PG, PG +NRG1, NRG1 +INS, INS +IGF1, IGF1 +ES, ES +EGF, EGF +DLL_i, DLL_i + + +### Model citation + +``` +@article{bbm-233, + author = {Taoma, Kittisak and Ruengjitchatchawalya, Marasri and Liangruksa, Monrudee and Laomettachit, Teeraphan}, + year = {2024}, + doi = {https://doi.org/10.1371/journal.pone.0298788}, + title = {Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy}, + publisher = {PLOS ONE} +} + + +``` + diff --git a/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/metadata.json b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/metadata.json new file mode 100644 index 0000000..d50915c --- /dev/null +++ b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/metadata.json @@ -0,0 +1,17 @@ +{ + "id": 233, + "name": "BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE", + "url-publication": "https://doi.org/10.1371/journal.pone.0298788", + "url-model": "https://github.com/Ktaoma/BoolSyn", + "keywords": [ + "source (?)", + "curated (?)", + "repaired (?)", + "multi-valued (?)" + ], + "variables": 109, + "inputs": 8, + "regulations": 260, + "notes": "### Modifications\n\nRemoved regulations:\nWNT1, WNT1\nPG, PG\nNRG1, NRG1\nINS, INS\nIGF1, IGF1\nES, ES\nEGF, EGF\nDLL_i, DLL_i\n", + "bib": "@article{bbm-233,\n\tauthor = {Taoma, Kittisak and Ruengjitchatchawalya, Marasri and Liangruksa, Monrudee and Laomettachit, Teeraphan},\n\tyear = {2024},\n\tdoi = {https://doi.org/10.1371/journal.pone.0298788},\n\ttitle = {Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy},\n\tpublisher = {PLOS ONE}\n}\n\n" +} \ No newline at end of file diff --git a/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.aeon b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.aeon new file mode 100644 index 0000000..d8edfc8 --- /dev/null +++ b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.aeon @@ -0,0 +1,369 @@ +v_GRB2 -? v_ABL1 +v_ABL1 -? v_ABL2 +v_EGF -? v_AKT_i +v_EGFR -? v_AKT_i +v_IGF1R -? v_AKT_i +v_IRS1 -? v_AKT_i +v_MTORC2_c -? v_AKT_i +v_PDPK1 -? v_AKT_i +v_PIP3 -? v_AKT_i +v_AXIN1 -? v_APC +v_DVL1 -? v_AXIN1 +v_GSK3B -? v_AXIN1 +v_AKT_i -? v_BAD +v_ERK_i -? v_BAD +v_PAK1 -? v_BAD +v_PIM -? v_BAD +v_BID -? v_BAK1 +v_BIM -? v_BAK1 +v_MCL1 -? v_BAK1 +v_P53 -? v_BAK1 +v_BID -? v_BAX +v_BIM -? v_BAX +v_MCL1 -? v_BAX +v_P53 -? v_BAX +v_BAD -? v_BCL2 +v_BIM -? v_BCL2 +v_CREB1 -? v_BCL2 +v_ERK_i -? v_BCL2 +v_BAD -? v_BCLXL +v_BIM -? v_BCLXL +v_CREB1 -? v_BCLXL +v_CASP8 -? v_BID +v_BCL2 -? v_BIM +v_BCLXL -? v_BIM +v_FOXO1 -? v_BIM +v_FOXO3 -? v_BIM +v_CASP8 -? v_CASP3 +v_CASP9 -? v_CASP3 +v_ERK_i -? v_CASP8 +v_FADD -? v_CASP8 +v_SRC -? v_CASP8 +v_AKT_i -? v_CASP9 +v_CASP3 -? v_CASP9 +v_CASP8 -? v_CASP9 +v_CYCS -? v_CASP9 +v_ERK_i -? v_CASP9 +v_CASP3 -? v_CDKN2A +v_MYC -? v_CDKN2A +v_SRC -? v_CDKN2A +v_ABL2 -? v_CEBPB +v_AKT_i -? v_CREB1 +v_SGK1 -? v_CREB1 +v_DC -? v_CTNNB1 +v_WNT1 -? v_CTNNB1 +v_CDKN2A -? v_CYCLIN_D_c +v_EIF4E -? v_CYCLIN_D_c +v_ERK_i -? v_CYCLIN_D_c +v_ESR1 -? v_CYCLIN_D_c +v_FOXO3 -? v_CYCLIN_D_c +v_GSK3B -? v_CYCLIN_D_c +v_IGF1 -? v_CYCLIN_D_c +v_KMT2D -? v_CYCLIN_D_c +v_MYC -? v_CYCLIN_D_c +v_NRG1 -? v_CYCLIN_D_c +v_P21 -? v_CYCLIN_D_c +v_TCF4 -? v_CYCLIN_D_c +v_TEAD1 -? v_CYCLIN_D_c +v_BAK1 -? v_CYCS +v_BAX -? v_CYCS +v_APC -? v_DC +v_GSK3B -? v_DC +v_FZD3 -? v_DVL1 +v_YAP1 -? v_DVL1 +v_PRB -? v_E2F1 +v_EGF -? v_EGFR +v_HER2 -? v_EGFR +v_HER3 -? v_EGFR +v_MEK_i -? v_EGFR +v_RELA -? v_EGFR +v_IVEBP1 -? v_EIF4E +v_MEK_i -? v_ERK_i +v_AKT_i -? v_ESR1 +v_ES -? v_ESR1 +v_FOXO3 -? v_ESR1 +v_KMT2D -? v_ESR1 +v_PGR -? v_ESR1 +v_FAS -? v_FADD +v_TRADD -? v_FADD +v_AKT_i -? v_FAS +v_FASLG -? v_FAS +v_P53 -? v_FAS +v_FASLG -? v_FASLG +v_FOXO3 -? v_FASLG +v_P53 -? v_FASLG +v_AKT_i -? v_FOXO1 +v_SGK1 -? v_FOXO1 +v_AKT_i -? v_FOXO3 +v_WNT1 -? v_FZD3 +v_STAT1 -? v_GATA3 +v_EGFR -? v_GRB2 +v_HER2 -? v_GRB2 +v_IRS1 -? v_GRB2 +v_SRC -? v_GRB2 +v_INSR -? v_GRB7 +v_PRKACA -? v_GRB7 +v_AKT_i -? v_GSK3B +v_ERK_i -? v_GSK3B +v_ESR1 -? v_HER2 +v_FOXO3 -? v_HER2 +v_HER3 -? v_HER2 +v_HER2 -? v_HER3 +v_NRG1 -? v_HER3 +v_NCID -? v_HES1 +v_NCID -? v_HEY1 +v_NF1 -? v_HRAS +v_PIP3 -? v_HRAS +v_SOS1 -? v_HRAS +v_ESR1 -? v_HSP90AA1 +v_PDPK1 -? v_HSP90AA1 +v_ESR1 -? v_IGF1R +v_FOXO3 -? v_IGF1R +v_IGF1 -? v_IGF1R +v_NOS3 -? v_IL1B +v_RELA -? v_IL1B +v_IL1B -? v_IL6 +v_IL6 -? v_IL6 +v_IL6 -? v_IL6R +v_STAT3 -? v_IL6R +v_STAT5 -? v_IL8 +v_FOXO3 -? v_INSR +v_INS -? v_INSR +v_IGF1R -? v_IRS1 +v_INSR -? v_IRS1 +v_S6K1 -? v_IRS1 +v_MTORC1_c -? v_IVEBP1 +v_ABL1 -? v_JAK2 +v_IL6R -? v_JAK2 +v_IL8 -? v_JAK2 +v_IRS1 -? v_JAK2 +v_ERK_i -? v_JUN +v_MAPK8 -? v_JUN +v_PPARG -? v_JUN +v_RELA -? v_JUN +v_AKT_i -? v_KMT2D +v_PAX7 -? v_KMT2D +v_EGFR -? v_KRT14 +v_PAK2 -? v_KRT14 +v_LCK -? v_LATS1 +v_NF2 -? v_LATS1 +v_AKT_i -? v_LCK +v_ERK_i -? v_LCK +v_RAC1 -? v_MAPK8 +v_RND1 -? v_MAPK8 +v_ERK_i -? v_MCL1 +v_GSK3B -? v_MCL1 +v_AKT_i -? v_MDM2 +v_P53 -? v_MDM2 +v_RAF1 -? v_MEK_i +v_IGF1 -? v_MTORC1_c +v_NRG1 -? v_MTORC1_c +v_PIM -? v_MTORC1_c +v_RHEB -? v_MTORC1_c +v_PIP3 -? v_MTORC2_c +v_S6K1 -? v_MTORC2_c +v_CTNNB1 -? v_MYC +v_EIF4E -? v_MYC +v_ERK_i -? v_MYC +v_ESR1 -? v_MYC +v_FOXO3 -? v_MYC +v_GSK3B -? v_MYC +v_IGF1 -? v_MYC +v_JAK2 -? v_MYC +v_KMT2D -? v_MYC +v_NRG1 -? v_MYC +v_PIM -? v_MYC +v_STAT3 -? v_MYC +v_HES1 -? v_MYOD1 +v_NF2 -? v_MYOD1 +v_HEY1 -? v_MYOG +v_MYOD1 -? v_MYOG +v_NOTCH1 -? v_NCID +v_SGK1 -? v_NEDD4L +v_TWIST1 -? v_NF1 +v_NEDD4L -? v_NF2 +v_NOTCH1 -? v_NFKB1 +v_AKT_i -? v_NOS3 +v_HSP90AA1 -? v_NOS3 +v_CTNNB1 -? v_NOTCH1 +v_DLL_i -? v_NOTCH1 +v_LCK -? v_NOTCH1 +v_AKT_i -? v_P21 +v_ERK_i -? v_P21 +v_MYC -? v_P21 +v_MDM2 -? v_P53 +v_PDPK1 -? v_PAK1 +v_RAC1 -? v_PAK1 +v_TCF4 -? v_PAK1 +v_RAC1 -? v_PAK2 +v_SRC -? v_PAK2 +v_MYOG -? v_PAX7 +v_IGF1R -? v_PDPK1 +v_PIP3 -? v_PDPK1 +v_ERK_i -? v_PGR +v_ESR1 -? v_PGR +v_PG -? v_PGR +v_EGFR -? v_PI3K_c +v_ESR1 -? v_PI3K_c +v_IGF1R -? v_PI3K_c +v_IRS1 -? v_PI3K_c +v_NFKB1 -? v_PIM +v_PI3K_c -? v_PIP3 +v_PTEN -? v_PIP3 +v_CEBPB -? v_PPARG +v_GATA3 -? v_PPARG +v_CYCLIN_D_c -? v_PRB +v_STK11 -? v_PRKAA2 +v_AKT_i -? v_PRKACA +v_WNT1 -? v_PRKACA +v_S6K1 -? v_PTEN +v_SRC -? v_PTEN +v_AKT_i -? v_RAC1 +v_DVL1 -? v_RAC1 +v_PI3K_c -? v_RAC1 +v_HRAS -? v_RAF1 +v_RAS_i -? v_RAF1 +v_PIP3 -? v_RAS_i +v_SOS1 -? v_RAS_i +v_NFKB1 -? v_RELA +v_PIM -? v_RELA +v_TSC2 -? v_RHEB +v_DVL1 -? v_RND1 +v_GRB7 -? v_RND1 +v_ERK_i -? v_S6K1 +v_MTORC1_c -? v_S6K1 +v_MTORC1_c -? v_SGK1 +v_MTORC2_c -? v_SGK1 +v_PDPK1 -? v_SGK1 +v_GRB2 -? v_SOS1 +v_PRKACA -? v_SRC +v_EGFR -? v_STAT1 +v_JAK2 -? v_STAT1 +v_SRC -? v_STAT1 +v_IL1B -? v_STAT3 +v_JAK2 -? v_STAT3 +v_MAPK8 -? v_STAT3 +v_SRC -? v_STAT3 +v_JAK2 -? v_STAT5 +v_ERK_i -? v_STK11 +v_FOXO3 -? v_STK11 +v_CTNNB1 -? v_TCF4 +v_JUN -? v_TCF4 +v_YAP1 -? v_TEAD1 +v_KRT14 -? v_TRADD +v_AKT_i -? v_TSC2 +v_ERK_i -? v_TSC2 +v_GSK3B -? v_TSC2 +v_PRKAA2 -? v_TSC2 +v_ERK_i -? v_TWIST1 +v_ABL1 -? v_YAP1 +v_LATS1 -? v_YAP1 +$v_ABL1: v_GRB2 +$v_ABL2: v_ABL1 +$v_AKT_i: (((v_MTORC2_c | v_PDPK1) & v_PIP3) & (v_IRS1 | (v_IGF1R | (v_EGFR & v_EGF)))) +$v_APC: v_AXIN1 +$v_AXIN1: (!v_DVL1 & v_GSK3B) +$v_BAD: !(v_PAK1 | (v_AKT_i | (v_ERK_i | v_PIM))) +$v_BAK1: (((v_BIM & v_P53) | v_BID) & !v_MCL1) +$v_BAX: (((v_BIM & v_P53) | v_BID) & !v_MCL1) +$v_BCL2: (!(v_BAD | v_BIM) & (v_CREB1 & v_ERK_i)) +$v_BCLXL: (!(v_BAD | v_BIM) & v_CREB1) +$v_BID: v_CASP8 +$v_BIM: (!(v_BCL2 | v_BCLXL) & (v_FOXO3 & v_FOXO1)) +$v_CASP3: (v_CASP9 & v_CASP8) +$v_CASP8: (v_FADD & !(v_ERK_i | v_SRC)) +$v_CASP9: (((v_CASP8 & v_CYCS) | v_CASP3) & !(v_AKT_i & v_ERK_i)) +$v_CDKN2A: (!(v_MYC | v_SRC) & v_CASP3) +$v_CEBPB: v_ABL2 +$v_CREB1: (v_AKT_i & v_SGK1) +$v_CTNNB1: (!v_DC & v_WNT1) +$v_CYCLIN_D_c: (((v_TCF4 | v_TEAD1) & !(v_GSK3B | (v_CDKN2A & v_P21))) | ((v_ESR1 & (v_KMT2D & v_FOXO3)) | ((v_MYC & v_EIF4E) | (v_MYC & (v_ERK_i & (v_IGF1 | v_NRG1)))))) +$v_CYCS: (v_BAK1 & v_BAX) +$v_DC: (v_APC & v_GSK3B) +$v_DVL1: (v_FZD3 & !v_YAP1) +$v_E2F1: !v_PRB +$v_EGFR: ((v_EGF & (v_RELA & (v_HER2 & v_HER3))) & !v_MEK_i) +$v_EIF4E: !v_IVEBP1 +$v_ERK_i: v_MEK_i +$v_ESR1: (v_ES | (v_AKT_i | (v_FOXO3 & (v_KMT2D & v_PGR)))) +$v_FADD: (v_TRADD & v_FAS) +$v_FAS: ((v_FASLG | v_P53) | !v_AKT_i) +$v_FASLG: (v_FASLG & (v_P53 & v_FOXO3)) +$v_FOXO1: !(v_SGK1 | v_AKT_i) +$v_FOXO3: !v_AKT_i +$v_FZD3: v_WNT1 +$v_GATA3: !v_STAT1 +$v_GRB2: ((v_IRS1 & v_SRC) & (v_EGFR & v_HER2)) +$v_GRB7: (v_INSR | !v_PRKACA) +$v_GSK3B: !(v_AKT_i | v_ERK_i) +$v_HER2: (v_HER3 | (v_FOXO3 & v_ESR1)) +$v_HER3: (v_NRG1 | v_HER2) +$v_HES1: v_NCID +$v_HEY1: v_NCID +$v_HRAS: ((v_SOS1 & v_PIP3) | !v_NF1) +$v_HSP90AA1: (!v_PDPK1 | v_ESR1) +$v_IGF1R: (v_IGF1 | (v_FOXO3 & v_ESR1)) +$v_IL1B: (v_NOS3 & v_RELA) +$v_IL6: (v_IL1B & v_IL6) +$v_IL6R: (v_IL6 | v_STAT3) +$v_IL8: v_STAT5 +$v_INSR: (v_INS & v_FOXO3) +$v_IRS1: (!v_S6K1 & (v_INSR & v_IGF1R)) +$v_IVEBP1: !v_MTORC1_c +$v_JAK2: ((v_IL6R & (v_ABL1 & v_IL8)) & v_IRS1) +$v_JUN: ((v_RELA & (v_MAPK8 & v_PPARG)) & v_ERK_i) +$v_KMT2D: (v_PAX7 | !v_AKT_i) +$v_KRT14: (v_PAK2 & v_EGFR) +$v_LATS1: (v_NF2 | v_LCK) +$v_LCK: (v_ERK_i | !v_AKT_i) +$v_MAPK8: (v_RAC1 & v_RND1) +$v_MCL1: (!v_GSK3B & v_ERK_i) +$v_MDM2: (v_P53 | v_AKT_i) +$v_MEK_i: v_RAF1 +$v_MTORC1_c: ((v_RHEB | v_PIM) | (v_NRG1 | v_IGF1)) +$v_MTORC2_c: (v_PIP3 | !v_S6K1) +$v_MYC: (((v_CTNNB1 | (v_PIM | v_ERK_i)) & !v_GSK3B) | ((v_STAT3 & v_JAK2) | ((v_ESR1 & (v_KMT2D & v_FOXO3)) | ((v_ERK_i & (v_IGF1 | v_NRG1)) | v_EIF4E)))) +$v_MYOD1: !(v_HES1 | v_NF2) +$v_MYOG: (!v_HEY1 | v_MYOD1) +$v_NCID: v_NOTCH1 +$v_NEDD4L: !v_SGK1 +$v_NF1: !v_TWIST1 +$v_NF2: v_NEDD4L +$v_NFKB1: v_NOTCH1 +$v_NOS3: (v_HSP90AA1 & v_AKT_i) +$v_NOTCH1: (v_DLL_i & (v_CTNNB1 & v_LCK)) +$v_P21: !(v_ERK_i | (v_AKT_i | v_MYC)) +$v_P53: !v_MDM2 +$v_PAK1: (v_TCF4 | (v_RAC1 | v_PDPK1)) +$v_PAK2: (v_RAC1 | v_SRC) +$v_PAX7: !v_MYOG +$v_PDPK1: (v_PIP3 | v_IGF1R) +$v_PGR: (v_PG | !(v_ESR1 & v_ERK_i)) +$v_PI3K_c: ((v_EGFR | v_ESR1) | (v_IRS1 & v_IGF1R)) +$v_PIM: v_NFKB1 +$v_PIP3: (v_PI3K_c | !v_PTEN) +$v_PPARG: (!v_GATA3 & v_CEBPB) +$v_PRB: !v_CYCLIN_D_c +$v_PRKAA2: v_STK11 +$v_PRKACA: (v_AKT_i & v_WNT1) +$v_PTEN: (v_S6K1 | !v_SRC) +$v_RAC1: ((v_PI3K_c & v_DVL1) & !v_AKT_i) +$v_RAF1: (v_HRAS | v_RAS_i) +$v_RAS_i: (v_SOS1 & v_PIP3) +$v_RELA: (v_NFKB1 | v_PIM) +$v_RHEB: !v_TSC2 +$v_RND1: (v_GRB7 | v_DVL1) +$v_S6K1: (v_MTORC1_c & v_ERK_i) +$v_SGK1: ((v_MTORC2_c & v_MTORC1_c) & v_PDPK1) +$v_SOS1: v_GRB2 +$v_SRC: v_PRKACA +$v_STAT1: (v_JAK2 & (v_SRC & v_EGFR)) +$v_STAT3: ((v_IL1B & v_MAPK8) | (v_JAK2 | v_SRC)) +$v_STAT5: v_JAK2 +$v_STK11: (!v_ERK_i & v_FOXO3) +$v_TCF4: (v_CTNNB1 & v_JUN) +$v_TEAD1: v_YAP1 +$v_TRADD: !v_KRT14 +$v_TSC2: (!(v_AKT_i & v_ERK_i) | (v_PRKAA2 | v_GSK3B)) +$v_TWIST1: v_ERK_i +$v_YAP1: (!v_LATS1 | v_ABL1) diff --git a/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.bnet b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.bnet new file mode 100644 index 0000000..121704f --- /dev/null +++ b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.bnet @@ -0,0 +1,110 @@ +targets,factors +v_ABL1, v_GRB2 +v_ABL2, v_ABL1 +v_AKT_i, (((v_MTORC2_c | v_PDPK1) & v_PIP3) & (v_IRS1 | (v_IGF1R | (v_EGFR & v_EGF)))) +v_APC, v_AXIN1 +v_AXIN1, (!v_DVL1 & v_GSK3B) +v_BAD, !(v_PAK1 | (v_AKT_i | (v_ERK_i | v_PIM))) +v_BAK1, (((v_BIM & v_P53) | v_BID) & !v_MCL1) +v_BAX, (((v_BIM & v_P53) | v_BID) & !v_MCL1) +v_BCL2, (!(v_BAD | v_BIM) & (v_CREB1 & v_ERK_i)) +v_BCLXL, (!(v_BAD | v_BIM) & v_CREB1) +v_BID, v_CASP8 +v_BIM, (!(v_BCL2 | v_BCLXL) & (v_FOXO3 & v_FOXO1)) +v_CASP3, (v_CASP9 & v_CASP8) +v_CASP8, (v_FADD & !(v_ERK_i | v_SRC)) +v_CASP9, (((v_CASP8 & v_CYCS) | v_CASP3) & !(v_AKT_i & v_ERK_i)) +v_CDKN2A, (!(v_MYC | v_SRC) & v_CASP3) +v_CEBPB, v_ABL2 +v_CREB1, (v_AKT_i & v_SGK1) +v_CTNNB1, (!v_DC & v_WNT1) +v_CYCLIN_D_c, (((v_TCF4 | v_TEAD1) & !(v_GSK3B | (v_CDKN2A & v_P21))) | ((v_ESR1 & (v_KMT2D & v_FOXO3)) | ((v_MYC & v_EIF4E) | (v_MYC & (v_ERK_i & (v_IGF1 | v_NRG1)))))) +v_CYCS, (v_BAK1 & v_BAX) +v_DC, (v_APC & v_GSK3B) +v_DVL1, (v_FZD3 & !v_YAP1) +v_E2F1, !v_PRB +v_EGFR, ((v_EGF & (v_RELA & (v_HER2 & v_HER3))) & !v_MEK_i) +v_EIF4E, !v_IVEBP1 +v_ERK_i, v_MEK_i +v_ESR1, (v_ES | (v_AKT_i | (v_FOXO3 & (v_KMT2D & v_PGR)))) +v_FADD, (v_TRADD & v_FAS) +v_FAS, ((v_FASLG | v_P53) | !v_AKT_i) +v_FASLG, (v_FASLG & (v_P53 & v_FOXO3)) +v_FOXO1, !(v_SGK1 | v_AKT_i) +v_FOXO3, !v_AKT_i +v_FZD3, v_WNT1 +v_GATA3, !v_STAT1 +v_GRB2, ((v_IRS1 & v_SRC) & (v_EGFR & v_HER2)) +v_GRB7, (v_INSR | !v_PRKACA) +v_GSK3B, !(v_AKT_i | v_ERK_i) +v_HER2, (v_HER3 | (v_FOXO3 & v_ESR1)) +v_HER3, (v_NRG1 | v_HER2) +v_HES1, v_NCID +v_HEY1, v_NCID +v_HRAS, ((v_SOS1 & v_PIP3) | !v_NF1) +v_HSP90AA1, (!v_PDPK1 | v_ESR1) +v_IGF1R, (v_IGF1 | (v_FOXO3 & v_ESR1)) +v_IL1B, (v_NOS3 & v_RELA) +v_IL6, (v_IL1B & v_IL6) +v_IL6R, (v_IL6 | v_STAT3) +v_IL8, v_STAT5 +v_INSR, (v_INS & v_FOXO3) +v_IRS1, (!v_S6K1 & (v_INSR & v_IGF1R)) +v_IVEBP1, !v_MTORC1_c +v_JAK2, ((v_IL6R & (v_ABL1 & v_IL8)) & v_IRS1) +v_JUN, ((v_RELA & (v_MAPK8 & v_PPARG)) & v_ERK_i) +v_KMT2D, (v_PAX7 | !v_AKT_i) +v_KRT14, (v_PAK2 & v_EGFR) +v_LATS1, (v_NF2 | v_LCK) +v_LCK, (v_ERK_i | !v_AKT_i) +v_MAPK8, (v_RAC1 & v_RND1) +v_MCL1, (!v_GSK3B & v_ERK_i) +v_MDM2, (v_P53 | v_AKT_i) +v_MEK_i, v_RAF1 +v_MTORC1_c, ((v_RHEB | v_PIM) | (v_NRG1 | v_IGF1)) +v_MTORC2_c, (v_PIP3 | !v_S6K1) +v_MYC, (((v_CTNNB1 | (v_PIM | v_ERK_i)) & !v_GSK3B) | ((v_STAT3 & v_JAK2) | ((v_ESR1 & (v_KMT2D & v_FOXO3)) | ((v_ERK_i & (v_IGF1 | v_NRG1)) | v_EIF4E)))) +v_MYOD1, !(v_HES1 | v_NF2) +v_MYOG, (!v_HEY1 | v_MYOD1) +v_NCID, v_NOTCH1 +v_NEDD4L, !v_SGK1 +v_NF1, !v_TWIST1 +v_NF2, v_NEDD4L +v_NFKB1, v_NOTCH1 +v_NOS3, (v_HSP90AA1 & v_AKT_i) +v_NOTCH1, (v_DLL_i & (v_CTNNB1 & v_LCK)) +v_P21, !(v_ERK_i | (v_AKT_i | v_MYC)) +v_P53, !v_MDM2 +v_PAK1, (v_TCF4 | (v_RAC1 | v_PDPK1)) +v_PAK2, (v_RAC1 | v_SRC) +v_PAX7, !v_MYOG +v_PDPK1, (v_PIP3 | v_IGF1R) +v_PGR, (v_PG | !(v_ESR1 & v_ERK_i)) +v_PI3K_c, ((v_EGFR | v_ESR1) | (v_IRS1 & v_IGF1R)) +v_PIM, v_NFKB1 +v_PIP3, (v_PI3K_c | !v_PTEN) +v_PPARG, (!v_GATA3 & v_CEBPB) +v_PRB, !v_CYCLIN_D_c +v_PRKAA2, v_STK11 +v_PRKACA, (v_AKT_i & v_WNT1) +v_PTEN, (v_S6K1 | !v_SRC) +v_RAC1, ((v_PI3K_c & v_DVL1) & !v_AKT_i) +v_RAF1, (v_HRAS | v_RAS_i) +v_RAS_i, (v_SOS1 & v_PIP3) +v_RELA, (v_NFKB1 | v_PIM) +v_RHEB, !v_TSC2 +v_RND1, (v_GRB7 | v_DVL1) +v_S6K1, (v_MTORC1_c & v_ERK_i) +v_SGK1, ((v_MTORC2_c & v_MTORC1_c) & v_PDPK1) +v_SOS1, v_GRB2 +v_SRC, v_PRKACA +v_STAT1, (v_JAK2 & (v_SRC & v_EGFR)) +v_STAT3, ((v_IL1B & v_MAPK8) | (v_JAK2 | v_SRC)) +v_STAT5, v_JAK2 +v_STK11, (!v_ERK_i & v_FOXO3) +v_TCF4, (v_CTNNB1 & v_JUN) +v_TEAD1, v_YAP1 +v_TRADD, !v_KRT14 +v_TSC2, (!(v_AKT_i & v_ERK_i) | (v_PRKAA2 | v_GSK3B)) +v_TWIST1, v_ERK_i +v_YAP1, (!v_LATS1 | v_ABL1) diff --git a/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.sbml b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.sbml new file mode 100644 index 0000000..be5786a --- /dev/null +++ b/models/[id-233]__[var-109]__[in-8]__[BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE]/model.sbml @@ -0,0 +1 @@ +v_GRB21v_ABL11v_MTORC2_c1v_PDPK11v_PIP31v_IRS11v_IGF1R1v_EGFR1v_EGF1v_AXIN11v_DVL11v_GSK3B1v_PAK11v_AKT_i1v_ERK_i1v_PIM1v_BIM1v_P531v_BID1v_MCL11v_BIM1v_P531v_BID1v_MCL11v_BAD1v_BIM1v_CREB11v_ERK_i1v_BAD1v_BIM1v_CREB11v_CASP81v_BCL21v_BCLXL1v_FOXO31v_FOXO11v_CASP91v_CASP81v_FADD1v_ERK_i1v_SRC1v_CASP81v_CYCS1v_CASP31v_AKT_i1v_ERK_i1v_MYC1v_SRC1v_CASP31v_ABL21v_AKT_i1v_SGK11v_DC1v_WNT11v_TCF41v_TEAD11v_GSK3B1v_CDKN2A1v_P211v_ESR11v_KMT2D1v_FOXO31v_MYC1v_EIF4E1v_MYC1v_ERK_i1v_IGF11v_NRG11v_BAK11v_BAX1v_APC1v_GSK3B1v_FZD31v_YAP11v_PRB1v_EGF1v_RELA1v_HER21v_HER31v_MEK_i1v_IVEBP11v_MEK_i1v_ES1v_AKT_i1v_FOXO31v_KMT2D1v_PGR1v_TRADD1v_FAS1v_FASLG1v_P531v_AKT_i1v_FASLG1v_P531v_FOXO31v_SGK11v_AKT_i1v_AKT_i1v_WNT11v_STAT11v_IRS11v_SRC1v_EGFR1v_HER21v_INSR1v_PRKACA1v_AKT_i1v_ERK_i1v_HER31v_FOXO31v_ESR11v_NRG11v_HER21v_NCID1v_NCID1v_SOS11v_PIP31v_NF11v_PDPK11v_ESR11v_IGF11v_FOXO31v_ESR11v_NOS31v_RELA1v_IL1B1v_IL61v_IL61v_STAT31v_STAT51v_INS1v_FOXO31v_S6K11v_INSR1v_IGF1R1v_MTORC1_c1v_IL6R1v_ABL11v_IL81v_IRS11v_RELA1v_MAPK81v_PPARG1v_ERK_i1v_PAX71v_AKT_i1v_PAK21v_EGFR1v_NF21v_LCK1v_ERK_i1v_AKT_i1v_RAC11v_RND11v_GSK3B1v_ERK_i1v_P531v_AKT_i1v_RAF11v_RHEB1v_PIM1v_NRG11v_IGF11v_PIP31v_S6K11v_CTNNB11v_PIM1v_ERK_i1v_GSK3B1v_STAT31v_JAK21v_ESR11v_KMT2D1v_FOXO31v_ERK_i1v_IGF11v_NRG11v_EIF4E1v_HES11v_NF21v_HEY11v_MYOD11v_NOTCH11v_SGK11v_TWIST11v_NEDD4L1v_NOTCH11v_HSP90AA11v_AKT_i1v_DLL_i1v_CTNNB11v_LCK1v_ERK_i1v_AKT_i1v_MYC1v_MDM21v_TCF41v_RAC11v_PDPK11v_RAC11v_SRC1v_MYOG1v_PIP31v_IGF1R1v_PG1v_ESR11v_ERK_i1v_EGFR1v_ESR11v_IRS11v_IGF1R1v_NFKB11v_PI3K_c1v_PTEN1v_GATA31v_CEBPB1v_CYCLIN_D_c1v_STK111v_AKT_i1v_WNT11v_S6K11v_SRC1v_PI3K_c1v_DVL11v_AKT_i1v_HRAS1v_RAS_i1v_SOS11v_PIP31v_NFKB11v_PIM1v_TSC21v_GRB71v_DVL11v_MTORC1_c1v_ERK_i1v_MTORC2_c1v_MTORC1_c1v_PDPK11v_GRB21v_PRKACA1v_JAK21v_SRC1v_EGFR1v_IL1B1v_MAPK81v_JAK21v_SRC1v_JAK21v_ERK_i1v_FOXO31v_CTNNB11v_JUN1v_YAP11v_KRT141v_AKT_i1v_ERK_i1v_PRKAA21v_GSK3B1v_ERK_i1v_LATS11v_ABL11 \ No newline at end of file diff --git a/models/summary.csv b/models/summary.csv index 36c902f..7af4fa9 100644 --- a/models/summary.csv +++ b/models/summary.csv @@ -229,3 +229,6 @@ ID, name, variables, regulations 228, INTEGRATION-OF-SIGNALING-AND-KINETIC-MODELS, 47, 9, 107 229, CALCIUM-SIGNALING-STOMATAL-CLOSURE, 52, 4, 128 230, HEPATOCYTE-GROWTH-FACTOR, 50, 5, 76 +231, BREAST-CANCER-SIGNALLING-PATHWAYS, 110, 7, 268 +232, BREAST-CANCER-PATHWAYS-MCF7-COMPLETE, 109, 8, 275 +233, BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE, 109, 8, 260 diff --git a/report/.~lock.online_only_table_1.xlsx# b/report/.~lock.online_only_table_1.xlsx# new file mode 100644 index 0000000..fc36eaf --- /dev/null +++ b/report/.~lock.online_only_table_1.xlsx# @@ -0,0 +1 @@ +,natalie,natalie-IdeaPad-5-Pro-14ITL6,21.09.2024 20:21,file:///home/natalie/.config/libreoffice/4; \ No newline at end of file diff --git a/report/online_only_table_1.xlsx b/report/online_only_table_1.xlsx index 9cb26730db1669b9fe76bb5697242ac7efd0f882..d986e5c5eaba19b06cb978d55f39c75cf96ba1bc 100644 GIT binary patch literal 58432 zcmaI61yI~i@;(fK;1=9HxI=IW5Zv7%1a}QC!Gk*lcXyY?-Q8u80KwgD-zDGs-Cey^ z|D%cz%kE6~^wZr>_sou>3=}jb1RNY3M1I^SEr|d6K?J`xa5S-YVrF`KR>XD7_p%@b zpLvGS-F;gB43|>~kd*|GaS(S=+7dK`=Jf?!-hRPAM~bZNjdJkuef?Gdl(l65vQWwB zhpK6XzH6s4@-FHdeRXhW<{Z!U8Ti00p=>8g=NPRZeLc1%Jd*F}93zdeeXxE2Q&5DC12>aKsg($PqtDdgdT$I+ZyEYWG+L}vUy%b z+->N{Ccy~qKojql(T%eN6g(srNx2WnWP7JW*t1PhWG@M$2fuz{w6^Ry+JC!-8E-=m zWHEF0l%w#Lls(PDB4Rg?4%g0n9^J!Gl!1i{O65pB1%oj04gx~){|OT+c!ZlZv#Xt> z)i*mkD<(G^>qwQ=s1+78?=y`rJ|Vizm}rJ#P(KqrW^32IUE<&!9FB*Gv6o6oX6+85 zzi-E!sGo?E#JMpEI+^Yn`#4qR-$4%`RD8p}h1&BQab}tmG&MNoYKOmKa7=V6!RkAH zm$c3R98*{!RIWfJUf19>{rFAb$~!Gl(P4G*6HOTAiYnnShv&uujGL_tM0q~R`|hQx zX2o)`Un!vODKRoO&4Xi2zaH$qA3KuAHnf(b*jFNwZsr7+ZhF2uSkv;&W4}7xa$c6* zXeUtyJw%sT>6`06MHvoF`A4`5mwFrqzOAVh}B~+_RL(FaQDHaTP*rD9mZ5OLG9{=$&*yyb@7$$ z*h>fP3EhYjzUaeMOp)t&_BT$1eQmM`F^#?)`@Sxz?us@Af#O35`QUUrg&E{Jzo%O-qOo_5>&RZ3j%if0Hs_ zydQO`yhWgN{I-nhPik$y6>-McdZs3$Jo~^bAQg*mjE}Gc`e{_elj>akrF5A}TXH6rw=O-=+ zo$Tys$^rq*UERYv#8mnh;3tz3+-N;h9A_$e#?4^#pF-;NF~YhOQ)$HeTr+sR5P1>d zUFAzVmtz(tqonDx%DT?DDcWKkOab#_kn~+ntib^1!GWxVC)k+=9FYTP!)M`b&;$z6 z$xkG}u``ftJn|Q@30Ffhow6rX8N!(nU4VU~SjCpjtg*32KsYk(v{J8Ygk!?FDZcHP zAp{^;U0&-#FEFX0)uKp%$Lfkamg=UhYukKqLj^?*v-^M`U_OuKHVm861|88Lqt4&U zJ>Ov(5G1Rn(A&fD;6D>(te^jm*WBW)mZBg%K)%lEyQMoZ;wKK!#N-Ix>wV(6KM3H)x`)eU`>w zi+%Iy&>iMG|HJfMv_(R5<=K${dY;*4D^)aMq-k`h-_F;|=5dXBZw}wp^)_3Q*DUg9 z*f&e#O;aCa_V_;WKyLyM)?@KJyjxG+AC$ zY<;{R=Xn5Um~jjvL@m7PMx`LO=DbIPb?I~d^9O&V7Ew(}wi^?GW%5%|(`;qOnv1sO z+N*W8&J5c=qz&`zD5o!OhEUY`)bAEj)Krt9+54f$(2@@AjkWJsR@=|P+VuQq873Ki zRyBh8G=WiH$DsBfwfac z)WHeH*Uz@16-<4YTQ*}I)88M%6Ul@{p;G^t@->Iv3@#K~!xq>MpZe`y2@Y2{jT$mI zc9-iNCt5B4dlrAnhR_?w+LvaFdIfpy@h|qjnMg+QB1h7%B{8oU1(Fou53;)f?{(v`$&EHi)Sli+s<6)aa6XxV63NS2eFcnvP7vWy|G?b&`49y_`}jOm^?f8rFh zDTu7k|IGN+Gf65C8Ti~tubAJ(q+dEj(iuw>w>#Ibil)W@T+WQE&g>KwC_N5skdz2Z2RV`Y(WovzFqnueh01Jgw$Z98+(Lnh;CF#K5m^EcgstS2 zBg7g+CDO!l>w|>nysDpojO)ba7cK12<^+oL>uLvj^4b2@otuKeiVWnQSbuI9IqbEp zvMr1qH>RgV`S@yv4};lbznwPH#>yW!Z1(N|VTE%6ft!Qb6IJZ^?uSVOo0HT~LNK9% zcy4gg(v#xSF z3~sU8F<@E__|X+Ia$pZ$c{(iVEBgv!*(R9R!q^*`PR`l-Q}n{B>L=BijAx)F1*11) zn9Genez{%#Gmxhsk}QJHhMS=9?9xs;QxNh|Z)`p$C)@b&rtQA_QIxNRW5y75#^{6T zgXMe$*U4q;vg+)7Zl?9643Aw@E4^%KaVYdn*>zn+VpP0Y>(x__$PbJ_|b< zfR5rHo}gc%OrlaeqVn{wVjgQ~H(7q!y#qFkEts`9i_)uT37QRXGYCZQxbxw8q3wS@ zPNH?O^3g&;48lPmLlD-butC^IBy~e{v8KWlK@Gw|B11m6uu*@3F-O~+OynU$_#6P? zTR9f01j2iF?_?q$gD?frl|}F5uj&T_@v57GL5|J=XWyo%sAZIt6o{rQ9L%qT&+O+jC+G`|Ceeqm8R4~Z?QJXtfXmc z#zbWDpSDxoJ2tn03vS=3p;0i9M^4isH=q`IX-b;;ziOLn@Q-PQqPqlT>PWg5t z6)1I)>+Iiw#a!sQT;)re;a{W#9gvA6Ao9sPJI%-(^B^1KbO~q?HMPr~bB!jaymsCv zgK9+O!z^`aE^F(P|Pswh&5 ze>7Tf%}o@Gz~RLQlPIUCD^iL}VK7pPLtzlv^4n|ZMrJmN9NJ5^--0Q8E@@xVk=9j7 z?yoqv153=UY@?$IJU6}4jfRiZ9V#&caY&DsiTrT`=uof+q=d(U`!O^{yq!P0jo|A3 ztdIEw<(JAqE1~m}kr0as7Z0jG+NM9u^IkXvm^;zj|9WQ=UBg$<-u#6xta*wg(VS!* zS7&5Y8J$Q>uXxf?TDYM7QLkS(j6k%Y==VVNLGre}E>mcn2rQ#53gnA*C5DxS5COfg zP+0kthK(k5i8xYZE}e6rKyYh&hMqca^(PCUl&~n}roww<^6B2AAL$+>mn5_p7iKoEx#7UbW>e@`91l&7>Q>dT5dmSsf+0LICe`|yBf=Xzlk({0QBU;X zhzK;?6&rkGBLg(6JVr!|EQxrW!)|^9y^RkRWj2_-!L|+q?KXpiCQ^R}-7(j*g+AN9 z_`FaD44oA%wfT9b^X&kJU2l~}{{AhOf` zSIde2Ps{mFpZVV>BLAEq#mZUzJwbZG62I%0f;EcZZjTVIdbx)jP}-jAl$%_Hmfb!v3le~!jYV&;MLS=p zWVC>+o?f4Q`F_Wh*VOq^qkY@43;0%})d`4w+?HcDnB=_be;fs*N%2zd$yL$R-SF$! zE<6CzNZcK+R-ZcC7{h8|n<~Ryxlm17UP4GQ>q5K|v0lbG4SGQjZOaw4=pF0cAHq(U zCinV9Gn2~-NW*iP%4_={3%OR07k2>!YV5WiPdD40PirNO6-%0PCiq(`0wQ*3^ooCv;bfbl+v>I`p}4 zfZ)moGfv$h%-oH9hps6Zu_l`dJGo~h@Tj zR(u=H<@c7Mq;@?~HSZ;x1p|+=aSs*Sh4AIvXTSO(FVxpICeMvjJnxBJ2H$IJx1*3< z(GJnl+%eBxQT5x`$Bmc5=Re!evxg+N*kY)_#^egm2ivCQ_5<(rUXd}6T_zozn>eVO zn-Sz+o35|?)nX=s_g2Xy!~&xWx(3U&uZ_`h%HRUS_zmZofBpQAZ0ZQ0V>f$+Cw8^Ix15fbDYs`Ph7Se{|A8K`+ zJY`ezk)qu2Z_5%zyX0dBNfuL2yRne6em74DW_7P$nOCL>ru14rc0ICQ-Vk{`6g`A2 zL7IaK;l%5Uk|XCM@~tjfTgWo4ORx zX9({^y2I9Fh3H4&)bd5FM~kMyMn{ zhPSvL@~HS;DdC|Mfk)b4t}EJMI4&xfwPfawIjp19-${ri3aA)7sOar{8@sFdtOmuC9#I|g@oR1H5>`#P* z!_E8WTdWS}OAqyJEAJipNpN$G@ww|Zgv+hT#PI#Gt2zZj1qFD;uK)_Nngu4*rb=bz zq;!SV6C*E7INxP@bNmCS=Y>1oK~<1{4vL3}N7KB^aZy38}izyhDVd6Z4HENb(xQx zh#(6M-(*`27I9lb=xuN)VuMAKR;!DM8da(7NSki}6bS>a2L`@Z?J!X|HGBel>|i?n zWW7uT#FrqEIF5cwMP!Uo79{`j+lkTAMqJcaKl_}~FOA0c>I3S?0W2;S2%OtC1uXUh z41R|g39~kq>Z-ufZ&3=aUkF-Nye8|NK(|lh59K4Z#x=;DtD%WFKd* zA%JamtQpvZOv6mpnP1GtR{CSI6=~+f{b2?XyJuH(rFl=;pb?4vmjEV2bg5X`_c$ID zup-}+-Ai0@nR$jF<@4{{jUbAOFZx1C9WY@U5et+=gwTm2$p)ZLFigmXlX67$XW*i{ zpfxILrq_Sn$FJnj1qiq}{u1TqZ7C202=cX|$#M*XVgjPO;Gtk3QxFyVP0VC7R%xKG zdjW-8M3JlgdF z3HnO6PgU&#I#{WPOV7WjC7&lQB%91n#a{Je3i7>IK&8O17cP*nk|K2V>&IOFOjYZ= z9m0B%f)T<2!Ho;k)^xM;Xa3jK{(%dkhEP_*d3JX3(AZ_dMrMAVWKFnYlH| z{}|o_t*zU~A?*=gm0f4usb5l;wOKqyLB$h7YmukQwaYnAN;}QDOQiERRuQRA+gc5k zgAFJ4+Vb$Uz92z=XEsj>9(P6isT`58WCrPKeu(2A7V=FaZMbwui58pngL(vZQv9F1 zj`em5+boU4j5|7Ly?Y(1a;~K`5H+PHT=q#7$!H(D#~TFiobfc?Ulf0_{Mv7Ygr zkonMD`A7z(TvDuKTN7>BBnfwZ9m9B{K1b0?S6NLWR;@l-c8Vyw`r91u$+fy4%qu(vqc{4uA79mhh( zM-OagRaeR}T^1&i7{Qg>F?d%m@MpR5@d?|hS#3a=%}Gd;_eZ!@v^p_5`aRNWJXf;HGrO zuzs9Veyv6o=lqR){c=5u_c*UBo|ERLL_uz%v#Mlw*jZN{WJhdFf0m%4P)mP(Ax6X- zL?rY0ULV0@B)Rw9KUj7sIsG(NaP6sshNNrSBkS&HnfY82n2H3s@+eqFg{7TX^jlt05Gy7zdm zFZ*Hth7Rgrl$T^&itnPOGRM~2AvMC?mj zF4cCrgML9#avxmPd>w;9QkO$aR>qXU%;rej<&(UPE8i!teNr8aqx<;% zOUZ7akRAZvdGngr_`-u^k5ydV)~;!uKhT9zjRIC`22>P77Uy!8R80@D zZI@RjpwWKU?A!456pvke2lzh*Czmv@>;*cV242ET6=N|Q0d|x`?}^Sc{Rz3nexw;$ zUZLFO#9!rN0Wt9$hLgf?&R)Ka-bw5NUajlUYl+HpOkQ(^sAU4}a#)7$qIPWXKUV%4 z(}nmL_Hj)oH|Ky2yxrfqK$#CEaNc~Ej2)CSGKA7!;}1Edg=|?yxgdoCRgOZH((3O!=W|dcEx|%k|>Ftv&Ka$riNvjP$+#^ zj+xYr5u5JxUlqSxlMj#@lW41-w(-M}ke+?15=JMpptUcM-bB@%hr!W~9K#+Em7<*J zizjI3SS#Ed!(R58i@C&?pTKiJva5#6|G>~vOa%q3|)9(`EaqCoCqF0!r zzk$qY!0?ygrxG_V^pKCff+)MjoauZ6M!Z`@q=Jc|vkqei#zfi5Djc%9p+1HH*YMbm z;Rml6GX_x%24So(YQ2pX_rL%ST=dm|HU)ioYF@TT$U=+U6r;suBUi7TWuHK)buSEFCl`-haxYmIj9V`HIRQeYjb6sT=ykc!HTAq z5BHQ7o3ocvku_nVwz2RZ47ze`VKKswvIx~pVZ8vdnm*ICc^wbU`703!@>sJ5QJTEL59t zpTj3iW$l^3A1eN~LZQ;pPS43}9~9i?l4Rm}37yxs`&hyh2Y4Uf zMFmXd?~W!~8nVxUcP$L#b01)6g)B)49mh^;$ZRB2J#8F0Rv8XsEYzh?-E{{-xeqk` zK|5v3PF3(O1A8An-Ls~SI|=jNuR>5tNGLeEDDVar`!+o4W1MRhp)`@pkYW@W4F`qFOE1LYYWL5|<^m1d-r=@6ZXO=xwLkh}zL49X~-yWW+}$2K$- zQ*IX3Mqf!Owr&(rLh|15X*N*SP{Yf|TI#S_e^9DwDKb}_Wou_4{$y?l-8><}qCJ$i zfYoeJl;-<@OBeSl;Apxb*m_bQy^Or-f$VuJh{9)6S!Mlsw4-8WJQ8zfmeSecI12-N zax!oK7oDGRT6&unTH(aKb~4_wQh?xDP(8VbHcz?`>5a*Its}vBh{Y9e7mNv^to1;| zhpN*+>rZ@snm4|e)enM0i;~!pwVEO}Y@r#fwX7~uK3a)E?ynWhDM>+uFKSRzhcrTh zasbPS+mUq9S!jJo_|kks)Fk&Eil$9c15HR~%^}Hoe%tQO?c;tK#0%#ga(qR4j0+)2 zrOap})R>|~Z~b$(uC0%hjEks7)tJnhWn{+`Sg@|_Rp$IY+d2|Xi!wzYyfk9Xs8M>R z^2Qb7>f5gsBUIBOVKPrzk@5X#0?fb6#TH2A)AqS~w_FtZFCxUo$LF~D1&-pQwWsUg z*Duw147U0X=E++`C2rR7=7@8GmMD4&M^5X4eQ#?Ucw_LNIj z78b<+>oEwES3fMCh>C*N0zcWnbuOMAk0TEEoY@we>*5pw74nM{l>_bijjr-T3VWh*5?eLY~Q=t z_%0CIo_4n#ADi2uYts1V@;qyO>em3+3Q8^2FKXh-wFZjWI_=#ONxI&27Z>l7(wK!P zrBubR+&||Y4d9ppiDC-JR=Q<}!iF3yy@}!TExTF_`D>wQrnM1s4?lUzV5^+Q9_V4qHAHAbm*@{k=}G&Jsb_U|=s9IzIqZ#u4_*+gqMSX(~&>+bT_ zRpBQUlCuMU46y#$$RxznI?=OQKJS1Q{*I+Jpr-r&^DYOm-0($Lexn&$2AjQHdksB_ z>sdzrucRLq4O+x#VN@gdjXA9w>YX-JcK8dBAEIf6M4~PNPgpghXN$=(3@S9{=Qxyx zTu5*>9@*O9if&RR_xhJpPuY45aObrP{Rrn@RT;MVMDyP96N@SL_`Z&*ep*AE#0<;z z0)gJnxhBh(UJB76AkHoR*9qVU@Hv;UospuWoxKyYk)5N-+xN^i${Pv+ENDJ=Rixe_ z@7PrczJ{g>wDcM4aCFSy4wNdU-f}jAfbR%eo130|t^vS?N z{1WGs_!~=NV0;(ZVw^@~a5`aktd>JOeD4>dt$9uu20D8`)R`#w_;|)#!vx-%pj5yR zUp)?2WCf3hxr}A={ocnZj;Nw~n4LI^BE7HX1794&623)n@afz@Dk~Oe!$d|=DT(;D z!!^2Spk9xVm{pvcZHnDvuhigRYxOQB=PIq6;d4Ap15QgklN!~ zKzE1-VIf_&Jl}bTk-RxXsq*BTG9&~<*#A6uMEh@t7~0#v`6DAn&aUU}D&G^9T3>^d zPNTmfe!ayCyak`Lc@v$C?$DeUjg->E9bz`*p9kZo2I5s_Jq3>;l+A$JLg9~0iZJ4u zC1aJsStmLjU$lO%NeXI0A@hoSwz~Z+)b@Qd&p+m)KRoiv;J$hwbPen{lzgp}v|ali zYod>Y^#(m;m3joeETx*#9CRU^xc}HX)=#Fsd9qg=x(e=foW_&skHmS5=3M7+5pg;z zD?=gb7GHOB<$D_PCnu1l&wue765O0@y|e`~oD(wJe_EwsmtSA3Jv|&ew#}ANc>eLz zSbt1k{L@fd?hdgFxgE1<-6cE@?F5vsfV6D~m=wUkDY_l0K7nCL2ZQ(jzSoEG-@qAt zcXGC~`HS5|4MGnKX3*Ap5!~{sDs1dbeKRk-55z@(SNG{yllfwTrDuhH(epcW` zv>a{ugJladJuL(yG72@L-Ae(tRQK@aSK`3zT^I&{%c3sD`=7&*;S8i!JVlt61xpi~ z$jLlLOcY{v%9#$z98nWJDaYH8@w}?@O3OhQ59D4v4;P1@USv>=H_q;Xc4VG5c|K;V zIB#}sEkOK82Cw=8{QJM{(h;?@bvCheHc)l9H*wN?v#VWgTmfuX=amLSduqdGH!l0; z=Ae>PUtP(`s=AiY40a$0=pstV8xj~aJJWIZ(Mj%2+FRUEW0EtD{(irz>U;mypfzcdt$C0~@T$Ubn zq)5;)TgnBNM^9a_#USKJoU2R8arIiPgf(|S)nAEZgi>9KenMoI_XmByZ?jC(g#G6Q zflAB)z2}Orsu!Z4hkh{tn<#+D^`eI&UHm}~I^AR`N=GCmNXR>%sK}cC@Y_fqg?X6+ z+-5!e0E58X!Yf^t%~VE{A79NF6i=lgnCW$WYw|^ird)kg{El?msa_;5@i!YWs!;RH zcO&XHc<&cZ9gz55p#)R!pVI6LA)Dj0Hz$F?IE8maOMgx;Kb*6dMIze82mO}w+Kt+u zgC?)mcV^y@XI0Ef$KST<^&=@8PnxiDuk{kW((#IkeH3DSfPQn>s6QuzJva!}Vg8rH zaKY~U*9Fsm-Q)Ss4W734@i@xC#PXJ`q90#B)ir;9@Z}ENNxYB+u?MHrgfy9bF%5x1 zkduU>K~khld%2EJq$!i-+X&@uG+)`%Z%h(dr;AFGC@up$oW1_>eZB8B^Ywfht=i~( zI=IW?GH82vu4@wVzB*k!^L@PA@O`ZUSv`>?PYONVyetZNKi#07`FK1%O@c0N7bih~ zNM4&ZUS8IjK^I2`zz%QFa(tIU=j-cLXPYnRO2feC;fTxE{pt5&r_aUdpC%!Jmtog4 zpNEU1I|a}mX3*3M zy77E7*d){rlG{mc67qU^wRq@!-F?dPm9qpr*u(;xI=x=*iaIT|C(AwxzTQ%2U8fRz z2>F1xyR6saKUJWYldO#n&|+2===lZY zaaTl5`f`!%d%vDc0{SiV3Pe_YJJM>_5F0-fAEWdQ|q&U_z^B+kL2??POK2oh`3`1LuO1az{Fng!hf z9=GWGvh@=3k)P;vof#gqIveH-dQcz{oF>Vn+<1B3LPNFlz2EBHxW1a~c<2(yx*mMJ zntVN42atfC#}|e8z2#@qG(cuz zx1#qIe`pra=Qhjt^})iCJ#m}M?cK1l7c{1vnhU%f zXlz04#y1FhL05rXYo~6lPpLJ0(wAoIU$f3Sy+O%E3e_*)(nBgOLKJ>`u}xmw27JnV zb-w@R@fZN|aFp{GeB4>L3vTXsSzRT`d=2>Xy?r1v>U@>5V+{K|WJ3TMwD<>f7l7<@ z|Mg<@QA3&@e0d;rAlwfq$L^9J3D~(9MgGpyojU zqfa~@lfm^>h{As7UCi%6(Wnu!r-v-Zp@ZLK)VncqSN+cl+&jC!$(TpTK=2_}Kren^ z`3u&@v&w6j+||V|l2=%im5zsR_#k*#xhNZsQO;!M%yZCd0LnpjhRf7J_~`C~?B#0b z)J8{0rw`}`9Im5)PTyN+Tf3PY->1Rn1M@0*%x^@U(`V^CnK(Z>w`L8VdoKjjC49XF zk7s?Kk1!sagxVg~lYO76d!i$Dxx}BsrgtJjHgMPJ#nae{hxZ)^q{Xw?IV+8Z@c2Fr zq&vj0?ncB%$V}LGvOa1=@R&Wv;z!;qRw0OamFnmGjQ(U#8+osrmrE|Vhc& zRcj!KcNNdKx^ikQ)Os~)Jdk9H$?jur@Dl0kk?VDLz59AYy(I)H18tDBRuQihf`okT zc3mfbTk)}GO6dHqc{;pE6km1ji7czAaWSZ<`ZVB+y&kyf^tc*4ETVtw>VBmZx!Z!>5APvx7zw*2|8}S5#Yi@A!OS=b5$^-DZVkUYYoSP1ZDtf_h<3zv(@6s$%<$mM?n zbtPGF&<6=@(<}it{;Pe*Nujp!@V46_R2_)KQXfc$rNt=}v{%2Bg&rJ-MO3G@B+ME& z57(!*MA74I=iTk``nN=JuiLK_G|n>Fr&dop=FA$iG;deU0U9$zDVOHQ0+@dGngI_ILx3Q|#Md>>n{#U(YU*ZSqii&8XmW+-Oy zvJp@4$e2n|HE?n)F`cS+yl_%BvTXSLuiaP3S>80#bOzzRP(`5_3zxBRT5^T{(doxe zDyec?n_>L4?J>)O;G3bt#@YLly~_zIIg+E^`D<6{6^;$Gz(QzG#*27_2#ro?%dc%( z_|Z2q)G8vgn@+JfdL&p;#|-L`0qpA%%BBLCB4IK0#I%>jW-7X~OAG93m7M*n316!| z`Y8L|lydRQAs!9aT3akVIT3Lw4L6@#`7o)z}WE2xaW7dQ}utU z{j8X7R;p_g))%(+M6q^{v^{|D%^UQqvR2&&l{aC z#jDVAE7;{>P2iEjz(Hmq0I;j3t*jw{)!DUFX_JG$)!wGY(ya10nW}b;F^HGx-OG^} z*!<*}B1(*f(qStVTe*VYh$_GqtS3Z+$vw$LiVyIs{>Sj_@`A((fSM@ByywqgvA}1! zPL6VNk3b}SW)k}u3Rr4^0?}W)YJgz9z=$pY6=j8)vV73Hqh;^Ff5TqWGB3q3FB2ME z@rA-FG`RgsbVQDBV8~6vrHHmd&JcRJ;iqW|qowsgk#4C;TWWkj=D$_Hr*79F5>si< zH(yd7dcsN$77znZ{*F|gDIzjLT9nA8ZH>GdM$Fnyz~wmIXqmP69>609FjFaV|h2aULuIX4t%e)xxVLB1Q=0E|AzP1H@u00|7+E1 z#`W{z5lLdf{KE{4X%WJO5lJ{J)DDkcs@%1EdY_`&j=owgn;@~7(TL1=B8YiR7B(-O zvRNmV-QHmX>(u<)la_#oY%7O);-gHWK+LB4kvd8?v--9f!Qr~ho>(CUjYx`4xuzr& zm=1?eWCsF(F|f}XMv=fiV_saP>(-aCwoAmbc^OpGG#xUyl^JC-!p*-+z!m{6mDn3k zDbmD8G&7Dy7$!{AjUolT`?G8!Zk3GJI5Mwa+4PTgI`)-A6Y)_tQ6N%BJp=oWz%FXV z4DnEUj=ga}nc~iiybky?{qMkrT}kllU^#~hJyS4zY1=l^)r;stC0*|GqY>)vmLf@b zZ;Fy8R7L{8q2|sY!W)h0ez>OXf_Etxq^A?*oVjiS#&1RM4Zq|go5X+8<*L*bj}d_6 z9&$EQJBqvedz6v6;rHl*PlQO$5P@-Hl3H-vhI13@_a$($cDcDE8kXr|A&>{_nb26p zx}wxKl}0prBu>|k#3;xzFqTEs#1E)=K=$ce;RUGW)z7$FvkmC;PTI0zBFMYD#80ot zfwimAfPHBUPL`7js=NxIalJL$PDO^yD3#HdE=6MOu1S8!os2Vtf|Ol>T(HOw@V%Ab z`Q>IBcoljk|FL~lM@?L(eZ*YLWJtzbW|Yq8OOIk@-)NC1W>g!Fe$G%~m)O6CH}+PCBY85`w5u6Ag99&0ESLc&3H)qRe4e6h_iK|--5MemjgQ^6 z8N`R0m~{@kvK}c>%)jCV4E!r$z^J=4Sw>WPL{8TX#89Uc7)7!UBUJqUk?&K*8IAGhc?aILXSOb_hbe`vnh$0I1`sHx2WH|I~D@UcW zXLQ3IK|&lUh@&z%aRAlBh0(N9Dc{PAy)W#}3H2XAn!xy{o@L}3NDrFb7`8V>0w5%U&!#$W{x z#7?Maqgb;KAQ;8nh0uXhRf-1-A>B*^7aZw@ZfWSp4Sfo9_WCync`A*5aaiJm2%>_x zw^LZh&;|C!?uCjw@8c_sLRbw$_yE0%G?$Kph$TG}aaS?(hj6#I}EE5Hb_+1^NZpY`~_Jt6BJ;*L14XDfAu2d)zSZ>_l?ZIxt8_pmulb=(IcfGC4oU(bAQTFd4%Ae zT(h)Pqj5WKRKZ8$p0s7b1Ovr|n*k=be`hs72U*;py?cN8>ktt`QYP|%n7-;kq6B>Y z6=u|PMv>wU&eH-taBC$WE%pQ%ryP>q`jg&L~p+BM;>Xj2^sdK%Dz-PPas zsvbG5QN`-9fa?fKC@_n3h;1snmZl}Ws_5~%OQ7c6S!^cBM$Q_NDLf-iH z=4TrX=S_aVD45ur0RQDb-?GvDGFQCz%P7QUlj~!)os2`&cE=Ju+w^k#bMLZa#ULkQ z021%yDVUqm&AKo}4KLZb! z6hoE2wbEV)=qiDZSw;BPoWe0P_zta4rf-|oQXnJkUzO&~nGs$U`MsWlI1|IUbz-$Szr6f^3*naGQK9>)ZBalendKcu-GBEfTYA z)syDHAuIX-$65>0a*`M>@U8z-Zz^LQ1Wi$O1AlnL6)jay*4{peOu4tpp+G2r51=DS@ zdX?nRXUiGj90*vqprOmS&Xl^i)dpwcz0`YP8PEdhm}AG?6mQ9b!w!u*0UHunw~?Hq zcUr~>px+_F z?u{b)y6W8bGio%K>5a(8pYU6T2W&}>6=_(q^sJFwYW^EUECSJ+Z$^sxJB;Cxe*NH$ zgC%M}qgVn*)(fXykUyvE*BZY?@zWKL{JY~p4(l+2V^dM3?&QjK>m{py+_;Qe%0&Q` zhTQV;f~|Vld}m=5HQ@5pwxtu?9%Y=B+T%;Dz_<`Zu8rF*CgeXIJN6bfcQbJzyzXf{ zNrF3i6V^*fhh{Z9r1_&rznkDSYIi(MJC4ha)evC|MEk^LpOYq$SWY0!EkR^kakJG? z>}egzVl}O8H6n_b7&alet^e0LHgU^v2q_Rz+|P#CYB$YyTn~GTF%d3#vwC8IDm3T7 zVobtI@p&+m=b7#4vxUvmOx)m%5Q$C8Sbl5M2<@;4jc)vnjJwI2RCUD*He)6s1tQv> znVNWfRJkv$G;%l`MSt0-;-j>H?kj1fu9lHQduZ$OPNaU^CfqCKNDt@o- z3E7j;p>5tSV*V*I_9eJYq&7mjlgzhYFrw`~N@AWPii3n!5|F2CH-zl&Dh3B+r!5lk zyF2#yKWeYVeh3>Nb3NhWOB$`tAL+?OZ-#sDr) z{yG&r*C9{O?yd3pr#So#NqxJBa;_a2grv9m^7(J`!Lh8;ig+MU02$jg}PC2YKjBa{=Hu)h+hDx*+$HdM#k<2dx;LP(SiRUofxVzZT_w|>qOJd;kXRD z`j`$Ek7PTo*?UdUv(l{(s~G zj>6V?E7^I^$k6s+uTS%AwC%xby_<&0yom0xVq0Gk1%m=Yg5Q><(0I1eo&PXaxLHqY zTO0oWXGdmEDr|zw6V=gtOoB_L%MdAA#vQ9qm?+~#_Qr#4a?%ZCB&@(s9}ffpE8v{2 zEd$RlRoua#2PVPaegkiJm#RFPSZh{e&Wg3E3RYtbN>SrybcR;{fcf=0mi(?`>FwS4 z6)dt}lc${4SX|5N!QR6zUoY!8^CLw-t=OS@5sjwsYCquhL`!j8WtV`C1d@5#$Hi-QN5*Tqpy; zZ9D-&K_cMTHXa;FSQQvF{6Usu5b2%s!9Xg}vaAdEyx(Q@t7$phZ1 z!!9_D;`MC*(;{sDmwxHCx9Q9Eg0drs96NQb2(W1vC4}w-8~N7+mlpAQDsiV^@_37Z z4Mo+R0D@b`_P=~2-}D$MbK~>7$43;%*`%A`BPzIlVXyQE{ZMzVL?QJ=n=X9nTcei{ z1~p#k!eJ;BM1EqXvesY8jfqvW1}4Wz*_FTax~tyrP@?aktLZSr7o7b6wf80PP`2OS zQd(%UXD|D{M3#^wlMvZS_BGiRkxVJc-q@umvJ}$TMaI4ik`}UsGAe6Lp<&Ft*UV_q zQ}g`a_x*kTpZEX9=aXl+@9W&>I@h_r=X}q(uSbNwSL-GvPVxS6Lo}0P)P^OPblY&u zfchzgF}@TFy#StRr*eSI7E_68da#$BM$4PC)=j51SRQ*}9A|+00^4h!{;?hLda&%} z0E}jU7IU=?l~KZj-u@w!Mq;Ra`WC3=1hV@W$rn^d1XKymU90x+HHjZNQN;-tnz8NW znLqKZnq%qyk|$|mt~F%tS|H0yZ@mdx|MZE5klq>81j@xE7HOIKY{ zyHk7KSJ4|jK)bTU$P;5T;-DV$cw)LWWcpfQ*O<3nKdpb}M1%SV?vI0^kk}nTf;Wx% zVbd8ecuLay_}Ke{?=DXXsEGS2+ZK}C1jrD3nr>)~Sdr03lA-=}G~>%=bV}5bDBf~r zefh`Lm5x<{RAEz;e(GE1r3Yf38+$QV?S_9V&!`7Ae)7)SU1=zxAug(6k2Dq6ROLqO z;1Zv2m*oW3a6M-vUqM}A5x?o+*e(02j15bD9AU?R2p&Ddv4-*aOT_w6Mh3SIKXg%} ztsa?ImF3-K>|reKYCP61oD}gazt!BGQ(TjeTS8Kp-CyN01eU}sp$X@nt$)S1N4`hg z*fqTBRZ}>jbYgku%rm$z+`G~!|KxpU5oRV4bm`r8bs^(1u^l^@vsh{|&%})x!UIiE zzIx$|eZjNgJFA@%S#k>Ai2K5Azb9zbgTlt*FC!9YA{fm^#F?{9VWpoN)csu!Ck9Y& zIv*o)6H=4!T_xBQKE(};GE*GEn7UfPivuIN{S|hc8)z#XlzM`CI^pV zYG~gS8zfJ!Tq13tA$_x2wiiwi>1#cXy!dGkyg7TB{`^l97jMBy7u-SPF z$E#p~XKfKeD|3wn5|Ng<|y7S}fg}^)D?(j|hVL^~!&Ki*hGrl1Xz5xa+o#yta z(UV7W?4b@R59-uR;+7Dc4yWsIQgN|07(EpwC%B z$T;fWH?ggwVrH56NBCS+~@u%D6dT#vXlfYSl0 z$nUi@ubP*Lj+aYGDa#Rotfx{EaO(Uip?x#PAlKDN){Nrus7gtgSI0dXV%&4C%iRiu zwCQ>EC0CF)&NmSXx7}%V>5f?!QalEQWlcP+9Lpro+Y23x`>{z0v)+1DROLMwG-mB z#hun8@#QICw8U)q_IxKli87$YOw)JbD?dD8IX*Ge-Z7(IV;zu^Fr%Kv%H?R;om85B z2uApq6aq|OIi`{X5`(!Zzk&f__p%7)A0a`2@zmq-V{_Y4nCs61iw+;XJ9uGlCa-ZK z4T__P^{C}nvwgAEcWkuo4qo1y?X3Uo3f0Zxi*M=PrR|_O^MH!os&)(2WZ1;hMvvyk zHmFQZV9u5uCK7gOJA{-)2a*p5Opne-<=fGT6z5D)0zogeQLUSb>4cUjlL}*p_X(YN z6(pZc5LXj2Z3#Zm$g7&iRKJ~94}JH10@d+(PY5&HsbW63w={BRoM{RRiun;FgM~3V z-l}t255c6KiNotB`oP3h`Vl@5;4}p2W&!TqJV|BapojQq=Pv;>UQ@gDp1uOB>8O)f%tb3 z+dEAkr}`h@?GPMDX+(AkdhFK9pBfY7I`&dSNzO&L`(xgXZBgTpstlo#n^f#c@(V-G zy)s0T_6MAEsWy5k<8j|_UsvcAHV5-K(@Hi63-CQ`1QPqTO3%OKN)E(WwxDF{0WiV% z6Fa9%(ONf`983I|L`J?+>Ij!a|Z z7~ES98EPXV_NY6EowN*W)B40I+_6^vq#o*?|GGnoi_SfMNZS_W9$$Wo&v@Q026n<< z_G+(SLeGXJb^&AeBbdO*Y<0zc^B6|YlWzvgGc8^)cm}Q$aGr#5`3BNvaOL$9Cc))k z1Jvhou!}S83)6kQ=^o79BG+qd-%~Ld(4rp_m%%nI;J9MQ8TTJ6Y2BP11bzMxamxOH z8J&n65A{umzsI%et|NR$rG?q6O%!0>(isT7yVj79%fnH!U@a}A`zI@zJOk?jz+&EH zQTgyRaxNnIs=7AM+qPKKN)}pM*0S{)FR0&btIn0#U-9adpnBwBvaN*t;2qBGmZE~T zH-fpFdk7NN2{7af)VzNh0megwZ0$uYfCX(MwmuhBjH!!oy!6n8-Bl@3BaxXVVAr(g zM_bh$&l$c*mOUvYxH8FxmifaCGMYPh;?UsH%zD(an&*QzWWqd00jKBaEIW)Gx@LSF zmcd5jvMUvAgeRQVP|>HPXFE^cVe=@HJhse~t#@LVKkErP5kH<2br64@t5(mE5A5g% zbH6B{x0j2-MHQL8NXotw9jR!n^f=;^T70?=PF#XJ93JyP0B5#dz%Kt$$D{d!(bt|w z>8H0k<8t9+2bl68E~qEY=C)=*qRzIiPt0n)!hD8fsE$Q;exka0yC5{Ey01}YE;Si) z%65#e3T#A`jJxjflvKFw!`*34@dj@D$(tbpH+fUj&rIi@pGvZQS| z`1;l0lD^QfO*|{n)&oAI_YTXf`ciki|aep=QIBXxp0kioXA@J9sA0oi$Y8 z$WmnrGei1E3gQKV9)SXjaUjF~;*h~2LIQnxniBPi6~>JA_|ob8A5es-$Nc0SdM z3iVMdx=;E^6#(4}pYXx=$|0-ZTy!FN$3M2~?fEp8d%Ysg(w4>7u*CYv%H&Hk3w*=~ z`|oMbdc`uif#k9vw&%ibkxFKS$J3hB4g_C7%ES&{w0zq-Ic?5u<|vwL_s#5)RA;}L z-LcxNrDSe0+4!EFeIA?uU?(X(`e<8+W;l)L!d*gMv{i|hHx^BqK5czP!s8ka8djE6 zB7p9gK35DoH7U2Z;8|~oQ;k5y}Hg7vs zE<2wmlmyUn7kzK%8Z9xh!A<$h+s*^o1;Z^Rnp`{)?}59?WyG8+6|nniQSflA7k3~2 zRlK0FXsg+eY44#)i-s!z)GwKPdR>k!r7Vc&xo}iuenwIwa$6WA+lVu8v>Y6a&SyR9 z9#O^@ivkmD9$&#*g8A4BgQ7j{>YhtYcS69UTT3)~zC9Y4fHTCsWLUh|g%`7ZUJNEG z$HcIAWt+`HiZv>k*ukU^)djqXAeij>sf0t2`KLsa?Exlx{{ezp$7)Gw(!bH)YLU22 zewZv1y{_hyv=AHSBbZP8{^3@4B zA};m}LN|yDO^BAn4kZ1Z+FNXgQt-a=yq(%X5x~8j_j%6V{nUI`?d^%1PR(GTQm* zL^Vj;)j=HQ;os9IiTyHm%fi_P_jmQFN`xh(=()4cUpK|*Dktmhsf!#F>}5^hha4z+ zcv@e^PL)2>)44g=4LN0JL0tTmY-jP9c8-ix5!90K{LeB~m$tBl3-eaCG~JI&wvGqG zryiX?Q9>AAu*FyORZho&o*zMKlke1|oYdoIjjfacgb<-2`S@A-$YM04evTuA7a!#s z7GFin0)YjyxsgIdZ`4YR1L+zz|82z1X;Vbl2cV@a!TWs=U;B^{i`q7&K_@;dc$3zI z?R-`k%nvnlgJH<@X`?e#t^#hIw|B|3my)#Yr8~|QhkaO4f!ZCY5V=`OxoVw%(o`no zjhGVkmH|bNu!KIZ!;yL=&Mm?G&EteXNBlqpTOO6EuiS@KdJ1g=02iYA5^I{mg<`Ye zq?-(q&b@x!jv+eGo{+;vwMvBp9ga5%vZt|kPP~nwT5$wYn2(&xOSZgcYrpO>0dmKZ zU%$RKrN>tnc_Qa>#PDPN##V_h7SBPb4&UW=%rnz05DOpqK8K30%SS=NWYzdZla{B; zi2wrjk$Po&)b1N=Jaf*|jEx#j1W24>NBtvIlA=xX2kRqQ5iFxEsSes!h{z8Kdm+XI zGX~j5>v5hRb$6iFx;kpaGsmnH^;G0SWPY*Vv52cg%mm;``XDiKC3vopnPU+i#PytT z&uy@cmsiB4>6|` z@yWz;2WjL_#W&|EX%>Il=xca_&A%EXjEZ}a42FCAGpt*JL+uuWHCN|J(Q_gxmiO$( zlxYcWU>^@3NIVjC#R=FSyADo50f@O=hv`RWZ7cBX{X_>Ksh;eWYt_0{a}STlRbraw z?#2F!_M|85$ez&`xt^?*>0g2Q*gm;fFP#ewQ2GEdCnS1u{XdI%1ZFQScpDNQsgkeQwpZyRrakqT#_S={9|BxzR{C#42L&Y?+?#n}b_yuLjGmHh|7e@}%>Uz9Zs|VkP%eX1I0x8!)8`)AsnSX_Fi5RRw0*(e+Y0vH>?Cot+P?O6 zuRZgwk8MlHgVf`mm=hc_QYhD!Vf!=yfUQ(Ukt?|xktG+_6~*GI~2qPk!*KlVSL-N}FX%&kD7-wGjjdsIn|M`xA(Nv0dhN1UF&g>j>>WWP9U>t$75Yk4XIG?LYBD^CURwBAWFXFk z;QksfGSMK9PdYPHV1!!;;zOr;_t1A=>tcH>C?JZ*af!!CTU@g$Uy$Hgt=Fj*!7CU zupX@}$-Evv`FhIwWB&+<8yqzIi4+f{>Vyv~1aXt^%?UrrxMy{(PA~x4)7P{V4OBN} zdICDzaEzbdS5iq@So0w$tueZBB+2^~5R*R3wY zUQv(qaD-fzI2F>c^jLsNawv5R04nQ}29Wtsbr>G6{Z;jK(n3^`N{>YenNROoeiWb7 z#|(7E*6LhC4#D*TsH3}@BB-V#eC5xS?soPORxAC$ZXu>`00GIO%s zQ~TLg6_erh(Z|bnA;TYj`@Ej~7hBbZy^LohR_$0ojUQ`kE^yE80}l5&qgr$My6M7W z(}zMS^{`Xt0YizP8X`XT_W2a*N6ah!Lc$t}o>|aDIuB!m5cM|MB{09PI#q9v*J+2S z#)wGz_9UGfzP*HGLAlM90M@>u&Q=7LK?3W3c+k>bq3MXhy|!S*qAMOs3yE#Cyp?tR z=>}nT_eyE_g*rFK^L3-qlq;M#5}1I%iN7J8hZTR;1z43dczP;r)lF^WX^V62yjzw6 zPqS~_l@$b&a_YSc{B;o=(F2(Z@dGhaxh(AY$PA%9H<@(wp4FJxHQ;TIV<8+4ihC{X zMbD{3*4G_42%yS+tgAVg5~9dCXnMR>n+g;yNxYI&*I}DvmWyQK4;1aR{R8&$vl^;fSyn4g3OP$)$P+l^Vu-hN7xZOIvQXU)R_o_6jJvqTF$((f& zrWisrLHW^>uc$qB9YPvYS@y*aa=U2(v%aF#?EZt>hx+CZ*PV>t4w=a=2GQn-eR71p z<4D8_9uTbbE=x>Apf_(#Z`CK*kgmCh6l?gt(c^c`seBz-L0f$EGIjJ==f@C6j_#SBF^wRz&DGwBEV}%-?xU>4M(;&bPfXN1bgLbQ+RC zOM@v}{kCxlh|x~gu3*zHfULKk$auabT1?{^C6egA9AZ&nz=Dfz(p|N{^Xt9>PtT#H z3?)jQ$B5JVUu^4mB)=sZHa~n9pbc^6eR%}30`os1Bn(E%?32u_uPeU9oONaNDiTC# z)8qB82r(8gy(>S(*ycsP4s{`$F<(o9>)GEBKerJw`ZPjQw}C!WzfRCnG}oG8`(xAN zbtkEXzd`i3EmvqQ4xmP^8YGAd+zlo3W7HkFuErasg(afyuq04JEb)E&2oy7z7+vJ- zRH^KIzD1YXNS|eDM`Ph#l|w^>1*6S&I=}D`WQRG~j5<6}2G=l$3cc=Nw$ispK~@L! ze$>6H1Q#`@m~8gJdQ3KyklP%-kw(KAtS8?p!MdrC_GSWQwpya`-SXP`BbN zn|iC?rBZdAL|jZspoGj+SMVB-t5?o-0+)A!j4_8?Stt_%y9Sl00m{p9@G5?=Z5T*q zcLcEc!|XTULF=SNs3He_d;nxbZhl^@ufMxikoV+gV|i?+Jh&3*H&0}UV7C$iBnu7o z510>i%(trT&|Jr}unrVO%zLYY)xdV?*KzO|fn){4xMvp7o_@EcK8^Y{}I9*mLim9P{ zaGv~N(~>F%EEtlKzyvwq3(^z!BT5I9PqSUSbKBSyZ8CZv7Lbxu-iX8sTG^MJKJf*l zXLgeS_hwr_A$9y*)bsinD)o-Q;%h0B%u>aGN1a~=p$;oJ48?$|`tx%Ep!mq3BO>A9 z9+pr=yRc9A#2F%2CZ#BVG=FoVr%`~RnccG;lWik-L8C!laS;d0kOmzhFF~%pwZV-r zz6vHp7|%>np*dLm$F_&LyAB)9+NSN;B8L>`CzQW;gL3q7lu0Qh7JlOGh-%$oP^kCO zt{dHccBnp*n4_k^50Vm<73eoEB#f6v3WM>|NcK2WzX;W+!_u)ly1nMyD93oA>=Dl+ z>sD&9kg5owpX>2{QeB}8j;^Se@q{b~$q;9X=@sd4R@s{A^|0zNw}WH+Y!P7(b&rus zRGrR#Qs25PgfhXL_&DaeWagADorrYi*7hA?3Ab1<``rAbSdUnq?I$!vv?XtV4BeYl zT62^+pH6`7d_o+L(=kWRvhc@zb<>8DAa}RuvDd zm}=?{%Q)5D$iFfV+p4-B^B83*CH6)t^khMAq)N{n2KY7`YFv*s%>Bi@Vw{u`!Lnld zgvP>aWInOK!#2G!=SNW-G!{mPjfHJGU>W1(?tsPuo1XiI+pzbLtXkOl>wxW7>Ak+1 zeX2WZ-qLZUJHjl#(jBo+2PGFdV+l{R*kF}9pJy+l!?UodpFm^5 zUlqw#m%Fi2BxSoNT^Hqh!GPGcB2eDBMPN_Q%zO{9Co-#dh{20IT+-MQqBpto9;p<* zTOt?EGCiMtkyPfC%dAWqC>=5VsmC-;>M^}05T-ux-MHi9{p-)-TNfcbb7;{jKCn~F zhMfW9X(JU{2f814d~0pIytF&KEAmaD?D|fN!51DESj!F+1V+_^{T)FY#G0jiDT0ws zyhMb3P&{6vG8A@Us)1vr`Su`mB^r~MgU-EU%RMeed)1~ z%LOOPK$386D$}_;imEh*SiB;9sIO}}X1>zjh?+Z{4!L(>jLBci*1jw65pWw@`Jmqs&A|_2#qV$(rI}Jf}wTP^W zWX*!#2}=mt%x_#~`c}y3RL~edCxGc4%rYuO7DW2+tq!Yu&o4E7CZZjRU`}{*WPTXn zgk|F~NL1MemH>?qzH+Xo;3bR_pwA3s(D6mJi)<{0_Y9r)mI)PA=!+h80mc$pS%GSH z-1s|&Vj~)XAvd>0iDrC|fKXOcU?ZVAcC=|AmW?19$Dt1YcHZQD+xi{ zhgJ)@g5gZ`ZhMHs9cjJ|S2iDsA{#8NKei$#gMd20`ud!+TNdSKC4owH|$iuujO9XD@Xz90oxx@xxN9@3M@c$`{$A zD|lSQQB*2%Q3zp&oJ~e6W(OWzwdPFV7vBxGBF9e~b8+<&fnWTjdi07gva0`9sUrAy z)q#tp19h-OVVg?m`g2R;&hFg5rE-IVoegr+caKm(0ddxr<3rDKRL4sYC#*L zY!K8HPhNF`9BkUZs4h(sMqc&bDRo@-mo@H+A0`STyT)lNGbFpl#JK@se{xUa8WZOR z%tdyM|IJV$T3S>kV+VtIZjp%=GZVm7m=6k`UAy$ptnNxt&FnqXN9~4?Byf z`lf6wQ5ad(f2$O-d9`~2b%?^qx+hSFD2(hHljgQ*wd4J|#=u4-VPx0%-wcJaW0}ms z!i1pqNUmRis<4IfXFQHq*^7$N#_$-BSDh&5$iJxGx+09M>c3U0&vZ3<@)+QV!pN@i zk!;co$*wVRZa^5>eGF_w6h?lH|HV-GfuaV>@hVa%U2P2gYIDAyGp!{g1S8( zfvXaC4b1njdp`&JP7Mj)jS>KWpnu?JRzVo`EyH|ifcv}$WqKV=A0I^}l>T#04n}>? zRwsn;nCsr68W@n#2gmFF;1tAB-xIpIczmFS0@GbANEua;0zdNrFzS19NSNzgb{hR4 zz#?{|=zmT$!Km+vCinvjT>8;eLMnjbTt~0s9$?gW*iA#H?+|JUj!y^71sLFGVgyEg z%iaG=W<$ee<_v-w;)f+sa=)b9y>{!qu`EC;f{-4`Xtr$ZRq~EalCy1f)c6&k5jG@Y zWC8m3O1X-z<^flQNW#cE_O_K7l67q2+<-8$jty)?6h<}(|C^zV47=#nV-e-}-~uhCReKV*%jerr+w(#rTPcV45Z#D?kWPTLwy z{dYdU)=dRXeG=Crbc)xysmOn}cz?|>Ky!C^t(&^mP0b;7in;#Wu3GD+l3wvqA$5vL z-PA95db@IwacbIkxN9qsPTapS)=CCCvQ3S zSz#nZ@D3*)miT-#?+LtKU=O@aj9Fw&Coo~9e| z{zo!_r?2Kc7ab76PsY77%f+hOFbP}z04Z?)H;^hb!SxDs6(7d{P%*6ezQlz4C!T#Q zV0oZZ>{^H|)J=1`gJupf%MJVqgbZuGJAoy}DqX4T5K4j?i2A0L9YAAQC*xy<7 z7>zjKpB93&VsN~J&ia9e;QnuW^E?WA0j)%nfDr5e6a5B=#QXoNhB3N{Dng(ojB!m! zgem6fo^N*PUNEaz-1BYL0Gf%{naS*Nt9)!k0u)XLCjJT$j82s^h1k3VXeqjoT$mzW z$Gs%8$4x}=E-0&lKZmKmLqwCAI|x&bsNsBUD!DL4ybdiUZ*A3;z`&0EEI3Xf9)10}@IWLW$RRknum2d~9d} z{vjC`{wqX)Odmifkt(E24bwGap9Hw3(5hpMvWWvaP$1 z!c+}{#CZUJA`_;DNc`&0VQRPlTa^GUC*#6@g$R)80|+H@9xiea3OEswU;PMB*Fd`fFZ^??9$cc>N6UCo&L9yuQ{`B0?xR zTL1_xMUXfT;7?>AbgifK147B!0u)OCgqA0OSMi3)K`8P1T2G1eGAOzJT9erU0HJm$ zD4}OW211F~*Lq4s2qkL^o5Tg(0m3_UUWASlXgo1}`2LFR`vFnQuWtFVwfUl3lOFrA;7D8;8i@ppU8x%wVu+CFh$N5Akzo$>8B=u zSMfZ^g(>3owVo0&Op&!kli3UiQ|>5Y&xlNzTI(r&doLPFvelpZYhH;hAk#O+>>%(b zG7w6Kcyk`ujiEh0~1+0>hvEzv$b~A=^sb! z$n}(nE{q@?3;WZtueGC2|2Q*9uBSwVP;zIsz)`2qYe${djynC1I&igi)af5#id;{L zl<5>5y{@PKe zU;d{C)+EJ%}Kq$GM5-HOscV=ttsMD_y`hVA7 z0}#4))M+(@lIlNn^8 z=`!PKy!$ZIVnP)c!gkrj6^lGC{rZ+uf7&vB{+J^-7C-bx`!2rFbTMH8T{xIv1z!~D z!GYglRVaSkzdWFgz&uyMVLzwi%ZG88a>U8y(FN#2l?r}l2LeB>vOHi2#SP8kMg$VWG>PyYTH+xSVwShxCbb99ja0i9swia6uQ| z;U}%|Vb~@v9Oj)0ZoUip6_ttq*pd!idY6v>3dO$lAV~Q%fLLyTE@Pm}g$S$@{^RG~ zD=OgEm}!*@q2Nk7)C@NngHZaE9)w#?N8qq6!#JD@ba}K(1z&D8CV_u5iyIj3MJ$ojiI2(n2sdG zDe&8|3oS9#I6Rhzt177)8-s0yVo@H;EmpYcg>?Lv=`QG}Ir`@kcn<8_VeCv&FWwYC zlZ5xj56$Afbm6}YSOs;f;4ocyYz_j`>45{*TbfkCe&P!9!F(u`NLu(Tm(=@q(L_Z# zXc7BzuF$;;x-3_RX<900F2vtrh6W4;eeMDVPsc6h^h$Wt3@4>?BId{54#bt??;yse z3&j!hBcBH@FW{eCF7HLj;oouLP%#Ls+VUh6*DwpkO{ND0;Lw+P3m-2n&dEDWfW z4`ZiiaUZLO@yor2h$UUT6kV-mUnA-L;fe zp)-!3Qfql@c@^t8`BT+4CRc8=&vWzR)(XDMn~Iq;kH^+|o8-JgZ}54T^+_arOwE|l zN><<|^{8ZyfVjj}+1bG`56Rp^@@YKm@s1&PcIv1w$?|8m|{CJWnazK-|jvW)wTPx)4# z*^-h*)wjj!9UVf_xhS>s>Q*%J`Z*NcUNP0?2OmT_3qL%vKb8(hm@#t~o}|p-8>yIi z+W$GO;;>FcE9@TaKy}&aAnK&|r)VE5g>){-sj6;8cm`x&Ii~f{=zYSq55kQ>`6k?s zha2r5(~0ri$nXfX%QzgYt>}G zb>s9|y9+NAK3KmMHZQVQPc(c#Pw}L2qg^k5$WB(-oh5vF#=O)NVdzKQN8c6(aBnE$ z(>Fd8Zt)=swJD0%s@PZHXk}x2_~`A5`93-^kvseHviPj$F;%f5qeY)b_HLuODAHF% zXWq1bT1*E&p6PL*h`v3+T47zj0j1pF>!3E(hn+Cibju1lF_YqB(|*fL=C0=|!5{n- znNoxtx6U80^yV{hXEO0a?%Yop|8b%UvWa3xyZ)nLKcO%UwjVZD31HWBaW*8#A`P)~2L*1=wDsg8OT%l!PQiOTs^xr9ER@>jl<~C2_R)kX6Qb z(^i^+^Zw^y<}{V1fkO}NJJO5&%o=j~YsNa#?Tg6sE{kP~o$!_gQU93Fb*gx=Rh?{Yu_9hCJ2UQVRPzIj?)NM1<}47CcH*JaN@8 z(@_Q?d4;a*xIs$G#v@75%3F0#A28m^=cX#!C7mGHJFXvT8%D$DrOG=~)4GW>zL)i@ zxHyc)DI|iPFZ4J!v*RAW{_r>*>e)ST4Aq9)UwwvSKFO+QjO zbI~rB_Wg+1z$Q4acn1x84pXRU5tAc4v7C!$+rT}zy;ykF4M<vKSal9spkDm-l#!SR;yN*SR%7Dmq=Xhla`>@zrOa|6+4 zqd&HuP4jMSgN($3o11g=!>nw5%LVA`Sq4z-vb|`}z1E4N@KB78sS#!Jm0Rvgj%g}_ zhGQ}(`X?*4uwSsvSuYsCFJ`RyuqnN)ykhj-)~iEPs;~xUzQm(+8=do%+8%W^ys7`l zNO^p0_X)3j6#ns$hhM|uqv6t|)B$&RgR1#lCib9OoHErNOf!^8;fC?x#;*$(m=ubP zb;Im?T;m=^+ztL5&?yr8+2yQGB6I$DS1+SNu`y+g{c`Oz(~_!g2aC6F!Nm5$q{*fS z!>?z@_J67p+ZosTiEXp;&4}KJYMx-ahdl{SsIjckEYrt9Wyh$+3KYv95jZ4CwsZs{vqe2a|kS|&dg7*L-G*%H7Q z1aq;ePjh9z$CRB&+bz9UE%~X54a+?y{;9UtumGDwY0jKr?6Mh@%fC^9vgj-rdtHF_ zh~s8@^x@&wt>6Y%wtLL{V@6*gE+Jvi4Z>S_U)Eo#rWQC_D!HeyUSD5KyEPA;Xh;q2 zk7?U#;}Ut(Nv5qOBe3;QKL2k2W8oSq_jmf+@p|33=)6x)YW%Hvq>;X-#e{24erm2P zh1bnm?e?S2-lt8?f(NyG!#vQQ55>(WZ@Mb!J-x;KW=gh0-LmPt?!{!?gJ;sO?-zI? zb2{+zEoS~&BY$1bMce2Ay5@()qsN{!LMb!WHJ!?-8d(0M(Xl_-dk_7q!%JJl7V|dH zZ$J4)WnK5hz2YO*-k~;>UGOZ&u^UnDkC#gjrZ=}A{CYU7LicukkoP;)69_oudYS=b)C1d{{TH&nq?9PaB}sASQZJgg*s!+=BWA)A?Dc4HeR)B7v> z1%^jHV9&@+N*eK_^aTR);b{r}{Tn)AULp5{-l4boYC~ru^aEMgubrhjJgfP@tlB@P zWDeQTsJ@*t`@I=$673t~OZ%(B_dUT>QKs!J8!ZpAHC@*Rrxb2-FGmFAUh}UpRNE@D zd%v;$XU?6O)U7%R)ar-&TXXgOOWyEn1~=wW@)RR|UVcEO-XD-VDBYx-DnR_Dv zpLZOpm`(T_l`GCmN2*oA(kJQuoc=P>oP zW=1ar?^VWK3dYGbBQwf@#n^3*yPLt!CTU{2@7WYg@9!Vjm#l!k!~id@ZSC62Xv>te z)#ocxO=GK=q<4v@a@_jx(TPvj(t7y>jpa|coZS+|BS-W6rEb3I{$U53tguun;VDt+ zyM$kBz068m=Y1>INI)_gD{3V0Fl@ntf+Y4?^c}VXViG49OZJ^AeW$)9Is=xaAAeBL z+%(N{*0ZzaBK}kVm0DPg19w6tBJ8@djzI#yt;4#ucJ!Ak1C`elwn=DHFcgUTw^h6< zPYOldGMTP${D_h9DmfUE6>_WVbSK;LKB>~$)|d4Xeq6w4!0vc1FW;*EUY@bB{~a_(uX=hSaB7>1k-`ML<_uVGY17ibHbL-*rq zRcb$_zPI#VHvdu>k8DAf%)`pFPQS72jy>;?xVMr*9Al!B*X-@pnq|4I!0$D0jr28t z^_UJ3`b{*86(<^du8vJLsxh}Fcy`y-PwTx#e}eHdF^QR(HjCeRFL34q{jU4sn}*zt z{b&UF8KS!i_kAjKZbR5+`rJ34!tJUlW6dhI6Vxe5{wT0$k}T{JeyK3S#nz@fBg7$1 z*5>#bI98+T{LWznPKa%MJ69RzgWeLe+_J4ge&NE7n69eV+uE%{&vsR#;VRVu{;w{y zb&U;7T}8-FHrURUS#d26y=|DY44f|B;(^^LYgbhrNX@d#4qyYq<=-_dBTSVnPGgO60n6eDlxL8A``x-R0~8M|uXDT>akf_<`^c(H zqKsy$GN!?5IWGxA8~3$o@$GYJJ!^Sv8Rmj1r#qUyN(b>;C1NMEi;l~;Mc2x`rT|*? zp_l8ShhsxXcU2#UZ^Y=uVcXIQEcSB%W~tNjJy(EFrTIza0|SyOF;mmy z^GtZo7N@ApliQmR1T7xHlhAq3P{A8mtg*zUeVtbb-sz<64_Gn+?-F zk0_;}$U3=+;<(m2N(KrBip`rhQ{0W+XBKip=Ee*K1;rCe3JMzV-_>7M-VUxl65@pK zzYcWS#W%hY4Dwq~L9t`iD1mhp6z5ze{5-r*+j@AM7C-0a`s-jzmy3tkHc(K+@1daB zwra2o5C;bPobh*c@cG@)829a$xv42AZl_XE@T?kIyXpILeViQ}&iF`>)F=KRMUeH| ziRgaB1Uv(R_`qaXR|%A+BMKx*`FT3OmD82~YB?K>_;`u}*!SnJWAvmsIoo(U*c+Vj zKIQK8+o|b2n6}ji#tR3U(EcodVjn*Rg}sN}ac>V#9|=1TZ-?Jm=J>fu!zD26CJ?c6 z)$nG4pN89bdj4+oXb;83Brxg|_y_d;=?gFT(`dW1K4(1KekY(kSXR^%Jlc5UuL637 zC@9R;JlxMXxSz2y^!Ie|vG|>UpWSrVPtT{IxF+)J%Kli><62bUfduEJq38yNGaDuR G^uGW~1|3BV(B&E)=mGyKgLTItCEeD~YvP_m4hZ15;8T;D8aUxW*WS5Y{B#d<^ zg^)c4W5_zTu^apNUGE{B?$3Sq`QyI7pWo;4aUMOc`;GT?U9a`|dOfde=Dwt{eFy87 zUAuN|5#}h@+p^)m1K`=oTI{;5iKC^BIp*8LNl_=1byO|Fruf7jhB205X5Ds6g99w* zS&_AxCz!t;wc&akSiv0M=253EY3aI^7geb=H(F(5hnxM~l*R4v;M-qzy0B%ABMvi< zqBDYzN#7&X)uBpPGa}W*(mOL=|f)Zrt>>zZhU>6 z%#e0j;nL#PQqOy*eYg2Yh6v>h3AS7~w@g)t0T@0p{_jhjH zvV~#$mMxclWJ*W0trfT!kMqbWctekB@d(4jep_dm+2p#SV zrh(mM0a>DcGW2HO;r(Mvc<%f$l&G1?3kr1osJ#L z;hY^yy<*1hbK@TzjcH2}fgQA2jmM)(9!n*GF-Y1z&!s`MQeH+$j&)KF64*Ws*|i+&t^DYPTn8sPu+rj8<3UvTDQ9 za>|ziw|4Q+D>SB&60E1bvD@71sVc1S%Gy8&&)L^Y11#g+j-GOgwB9lT*lY>7E@fd@ z3W(GVU!I*!67!hM4Kf^DUB<6Uh!DmvDCXTO6veN&7|$)10L(uLRV*>_YfQ( zi+QnJGsCw$QRzve7?9_RJzeyBJ!7!$b8~xVE%y~JF6@h8ZdIgBXxS((RK+OKdi{z# zm%4`>jh8!&m*&cfJc?U8s3Q-SXGUprtd2!Ic`+gL6Zu%r*}3IHUAcXW!%`h?(*tsG zOH<25vw<f@nsxXzD}VhJ_enfY zT|oi1UMIjZd@{Dr`O?Bfp}mx9RDM$d+VC_Dcbj^7ME;el(#=_lG;J|pHbF~iX88k$ zlE-*ihbM5O=j4)>s;AIggXbba%id!)w>61M8)IB5<1_XE#`KV#f{o8A*RlJm2q8T$ z=bWokFJTah)cLIAlzeqoRyO&netf8}zwcQg2O*W@T}8*-;=*2Z8SBUAS`Wru5Y6Xg zD>pM_F;>U45MJx#S`T|JDAxx+nTc9jY>?}l!&%0lBd8SA)dWAN- zP_+1Zeux9)!K8W7+?*UGYl*bTvfNlRTD3f`)V)j_^q6Utq%F@bkv->}0}UNpKJ1g4 z_DCL|t3iJ#MYJED#7e)6nb%Maoiui&VchL%NasXI>qCx4 z+Qjox4da>lLsirM#6rB`$UaLk^c&A5wv;JCw!=~w4qvdd8!O#c|71#-CLtEO&ymJf zX(UN0%38d&XWr+7f)e)#<->T!d^TZJyG*OXtPVco78O%?%(&I+!M>v%7vV0V1J$|0 zMT^BVy}~)eBSLyP?9J-b-ii@^uC@&H?geabI<12DMz6)&awDmjG7k^SSDuoM957{7 zUS1eV>DXeJR($s%T%h#Pj67;&LPD zg@{ClnnVX>?Qt1rJL|z-rirZ6N)PyCtt!b+C}+fY3|;1g--J(RS6e5S{|ScN5fi-t z{)o@^7{`V>T1#DF|FL%Kz-S))qM!@KFO-1eF%WW|%6t*gw{zJm!5oeyr{h~1+lOD3 z|Jgo#6YX)SM2Xw@Or4SRGbS=EG4(@6>iIgosh*Q>QVBsdac)vdaIdG(@ROz@tgemPV$3f| zj56zL8|cWlIE#xX%U9>9XD4VYmg1LAvNJb)9LSE-=)GNRM%0nSOW`gzHfsiN*tzXh zA1UpodeN&mlg8Tg3F*#Xn*8g#-_s5-g)3e^-%!!*Rq2q*NyI@Smwuag)o|`WM=rc7 z-@WlEP51ovl(_p~hogvN31#tfykR>#Cdfevae=+JtIfFd{VCU5>@2LsDi!D77#m~; zYEoNsb5Cc6JF2D#ilqJ-t#@8K<%0}-pl)p6AjA8~P$f0tAeN|9<|HFrR%3H}2r#xo zHZXQXfMnEg76xN}J8P63ZfIb%xJ$vn#fUWhG(`jzzSa0Az8y6&d^gIokG;vX%gq~7 zgInbrrCJ`PNb(pEdx6DziuS>9^zHGO+*ZfX6cL0d?b3opa7tyG00K48uxF8*DcW<& zyxg_muY`muZ?T~!T&@AJ59r=1848S6lxe{S$>3^^$tqE{OsFc+j#kx(NEu3lu`9B9 z)}c`m8nxTCUK_R=Av{s(C`=Zv%B&$S3njYH|G~quP7#V!YIWbu4pbU0GuNQiNCcH; zlY_hJbWwib7kSdnv)L6%VUlnuq@gv@C>4bPhC@X_h8wVGC`Za=J4(VAY%p0}>cT5i z^Ke(MUX(VU|JA8CqBX*Jn}$Z{kjufI)>ctS`EQC3hqA9k>8Mc}mDGDvBh-(eEpL!# zv^4#E5+{E1>8RyGz3^E%TGyBQowIE^ z*@?WNAWKH&!T#MhH3I#LhLnKs6smC_cV4K7>3Tv|mcM7ikL0ce0^H6sivY^oLdpki zRGuFwZ=01+UXnglM}P0AJU7yX5YAtHykB$9@S;yj*+2;8R?C!4(YxAK=1|1q8$Z9FXSZIB%Kh`QJA(FP0Y=|o{YjCwP1iRmE zQRTZ=TBO*jD&R_KYu7g#A$8d%lqfF@bXwfrOPCZ9XgiAJ{?$p=XyO)UW57=w2E*3( zD-#{fxs0kMbJoH&BmZ`00Ykaz_Q%^k@$xsHyN!6PBsHasu#!KOFK!~4<)IzHb^)GCw?H~cVN zyv01iP!dlRJCRedbRU;%wgSQqj(s7nQrSk9Hsh_4KJmE{Mq+zz6-PbKJ?adi)VP8a zC!YQ1koVSV$!u#EM_g{NHD=vI`Er;_e1xH9o6ZGHWnEid`+nM>&me5-*cDI1id=LN|JKN&&dq>(tW=3ps>q*aDXK&eMmxfyTEvWmU95reU z{D6r{z$?~{m5KL(l|U{f#-FajUdKj}qVjv&Nh0t(!+?>H_%Ub0;(3C-U_wyT zvc_r~ca;dPSu#5kWdm)PyRzW`ePV8JdzA=0+%TXo1gL3xol{tZm%<(x%-+yu>W9Jr zA<_SIj=Zi5Fd{)9wIDCK-gGjtq@@M!DWW-!t2HGOZK=J6l01ev?`!A^`JZ}iEtqE7_R6jq13U{1Re+g zvm~SFbj~7(K#lu;*)a<8d(+0}uLW^Xf3A786DzK7v{X{LZS|MgdqvTC7xIAsTu|12 z6X2i`jr4UQ;eCnHpZm1#gRPo-ygffwE-GHwie1`YFyWM1($Eu*Ohe#cqG;pyW)1I& z{GrmE#=rX@gKvEq=Lp>dH-3Dx(^NgZJ33dt@)UMx-w_h27#h9~Cox!%Q z&3`PNHNeY_uJh zTL6$6z(wD+hGD21pgKy1dS>UkSz_w0xj3~Nv1q1v`J%m~Ilp{9hTRaG^{Dlb42VcBT6Xw}xjVOez#Zlg@Gu#*rY z@H^rf8e23&VLsIkd0_8cC5yN2kfTUZ4UKp?1Y*E$ocXrtO!?)Nzsl@ShkIdlI=Vt z7+UR!3zpD8x-Oo;r}g#DtLA1@rBzGjTg%$vT7b=W8O)s^-T?JsWaM+&2x)jwJ;RS{ zvHz*S`ywNTmuYrZF1?HmiTflp3;?0h=KX2eHY=5)jN7onH?Osko*_v2Eseo9IJErv zc&gI+I4_R127By9|Fr;0dJD55!2K9=^Ohq_n=B=ElWVSHi88LN#hDSXkv+5mge7Hz?LcDH%(^gNWX^aa;!! zuiECujg6!^AVWuEum{KTb4A&C@NO14i-llTw|Bt$gGRlWU4g7DvPy!(B8#I%mN)_J zAF>{@BO}MLBczGJkMTX0&i0uF;a0Eetpw2W*F!1fawdb@X>tZ&GR~4>T~q17m=AnN zE%;bhF_T4cZn2_!!5K-)CpQL1!&Pfi;>nHT($l|aJt8la-Al?=U@DCJW1!zfg7D>a zRt5@Njl)Aupy8tbE zN%yyQc7@?qJq@ibO`%J_I7Bc zO%~2Oj;4s=#Z-36yOb>CB_i15n{lj$FORrQCrp+c>aP>7CP?fY%HpVLxsqqC80gNPX&XQiE+t4v+@zqo zL95g*2?Uv4Ysx3L<}5{xHx_XjyIZ=A=TqyTciF)Li9r+Ih>3zj`nBpkXRrs13Eat9 z+5T8CeK`I+n#{97({90XPvZwxJkYjvl#ZZD7O~7ejv$Oqd4PO3OByaA5sd(zTg)EyUPz{iA8bI`j1)AIFDK=dfyme zBMya&XHjvKMj{SCK|2n=3PT@TXYcgTs;Pq=DBwoCODhs@>WaW*0xvEcw zMdfjPmn)(n5%>Ua?J|n$NXd2=TZe*dfQ2lHJf!=mG=VTQ8=~!uXOhgPx96!KXITW5a zE&ErJ?Kt{vPs{b&SsY5`_q&`BEJ;o89SVLTj=vo^(HsCJ@bY9l9Y#MybxRb;A)HH&wI8{0`5 z=TtBAYuO(Nz4^cZd;eDE(?_-o@24}q1`E&sR5FoQs+oEp<-C`gg_Pv^37|-z;HAx)(w@3AO46y zLS4GEgkk1BEozr@4hH|HBf;tzLM+iq{wLro{;UG#;>NDvGxyzdLt~$P$=%~Sw6el9 zr!}EcQFae-BZpFt5}#-Nb9bk=95o-JC=vxkH$_F(>U_J6MLv_fQa=;hg?(F zy}lHCSPW2|%4to6RHtve1f+%v;6F%x14!Lvf++aOaIB)Lf+Jc}8nor#a5v)PRBuzwdsk z=yy?-hB8(uSw7c9u*ka*0UMR%Q6VmKqPCCbSpO`ClKX=?sGsJMuso&WXgbrb71!(9 zO*+k`QDgnWTv8~yMIw60{y2>9#&-Ap1-}pkXF~{y$Ky@I5$9hw)n!KG>LjbIWgp@! zZ(!+1BOn($`tKTV9ZhVx8h*pgrt6x{#SE+82}4)&6y0vN`P3C&yjWYIy`)ld`dSc- zY{^Bb{5Tx{!NT>%sy9th?Yh${!Z44S&!zRJxdxv3`eOXoUwB9gSfrAlH~w zzHGih`1ICZ9G`>|cTXoN0v%8{=Te{ z92syuH-9fx;Ez5S%v73|Yc^ytueEAb85Y$^b@zOyOo%X))XlzKY~T{9ZuK>v{v=hJ zPml~j5-(s;It7v+ANt>KnFYukc=$=5lcJCwQG&sW2lnA+#sG+I3qus$8fULfJ^`m( z@xfZl`Hhkxdc+GUD4o}mA20a_U-(pqYu%wBM7H*Abf{7@P;GeAs?sphN&&W9oek00 zIe)$IMVl=DghrJQ^CzKgej2oAg@@H?u@y|*;e0O@G?8SK-kN5jHe|u6x2na>jFqz@ z5Z>_v-Ae=hA;#mQNoTwKPvRpm+LqPhK{H{j80Joupn;3-VHbxi*)xAREiG8e9gRa{ z(_x9|Y@(`9xn$p3lRC*&wQqUK<})neq*Q%a1nV{C0hJ(1zWaW8rGXsf6`??Z{ZzD6Lgz-il=@OKqI6-}7{N86~5<+U9KzKWy%Z@PB{iozoAj z>Sr;}zRoS4JZn|ttLdBX;BTQXKt#}8c0J#!%R;jol-Whv0yVl5Yb@IJ`2?9gSix0IZ6TsKIC>%`mZz?O&U zPIQ#A5h6(=`DeperI;TJ1yOJy6DP(wZt!{@i(nOFz6*X;0!}a*Oy1(9=SIzgP-4|k zcaNK)Y6W$bz@&;|HAj(cIxe>t$0tt;BHJXEd+dcsN0`TgoRwRTTl9vstEG3P{d{QX zy5VimV1W>V9@fA$FQY5bQP@T(RT_Dl8pbL-GOx2lP@6SU526SxFc~~(d1g_9;3L1) z#IcwIXjYWH2p(2431mT%oPdpsV^?DRgKicAUr^V_LtbV=_+RrNeGcs(eMymsctcjtZECN~voX zTvkU1M9+7#K1DyJhQAwgdDY&|koiZ#ouWdd6OzYy_s1EU#LGW|%`#^mxOW;s%PlLW zBl33h3A;TRntbaUL@4BGeLj!?pBcc%+eO(RT>Y;*Dd?gR+nvu>ek~s zTeH}c&QX_cj((Cg=%5&C2)jwoEff+pk&rg!)47l5SS|c#l)Ld3@;rF$LtLKtr-M59 zEPqE4wXOIFCT!H6+D0pE-A^gUu6B?HyzkqjgfzIduq8Hw{j$JxIxq z5JfZ`Fo5Dn!Jz)`Os)KaV$Fq+B=e*!k|afF5!v~nyd#?=IU?ltdQ2@1K>XX@x`7rI&1q zdb2wEN-+gZ({cUtzvgMWj_CZAcG#**2QLAW3zWh#L>%oHbDZzh`GhkT3k$N(#1TV3 z>(1Vqm_cQy(vAP>b&M9$YT;_8J1Z*bnxoKlBDUyL^s8*8&#ey%ay&F6CcTpq<%N25 zJ{1~c1qM5)($&8Od&=Kfgy(og*-QT1h zO?z*<8!UVy8nR#Et2D@W=zL25n(x#J5yg#G$lnQUhS<1N!f#PP1NZQ`p*H1rX-r7x z_Bp{v2%i*!juF1J@FsmaB@a)#+(U`z zH0L`K=t(*5OcO7P+*W6IL{BHAMYQr53=7^Yd7crd1i2vjtp{-5fVVPXmtVm7hHjm| z5)T(b`zr~2{3}&AR4F?U+ztug;fwu&=cTcC52!bittAXrr;f7)R`<>9hQfya zc+FeO);)DRn-`%CtToo}wDV)P&Zp83kI-Hvi8&JI-l;l&z7p%@A(r&KX~tK>e3G93 z9gYj_1ob7S7KVgTw$QX(`+@M{1S>C%vZDMz?L!OIbFeV$Rx)B&W+79I*1|$sj-5JD zSTw3?lua>m(VhNC7rLT`QkAMfU=>9iHj+j1j7x)%pFNuRvt#m2fyv_1hQhuC|FV=J zAUD|No80ur_@1o5eD^3)xs|)v#XOZTyTwRFP48hj2FKenQ4X?VXlvbhQQj*_u-m>G zNtyVr`j*vfgC5-qhJ)&nKxUjAk@`Xha6)3jlHn#jXEy#w}cinYMtX&*8yHGCdO9rMiD#j1_m75Sw6 zme5UitdqTD5uBc4&?6lot=x;I2V09%ti0i6S}kC1VRsS%ml@_1-_0OcTixq@N2*s8 zL@Cu5{%vFW-G-~=SXb*M4R8&24b4N&?DOlB=tkf+!4a6;2j@GHtGgVnCWzn1Rn zwb?UZAp#v8vkE(0>`|SKS;Z;c=tR24*fchdN=wf+?`KI)ndja;ZR=(I(u%x2xEi5E z=y5H+zhrr96Lu#BgsyBHnWu+@CAn8Id25TN{<53$AP8(cw=VWv1=}~Bqtue!D3fyzYY zlr%QMBm-i}PRDTb!}3B%N=BrwL5DE%TX=VrDCrEimZY%A7fwAfGG535MoSwTj2s*6 zPXz|=Uyulzn${t?Usbwrcf$Idpheh7R-~_b2cjfp6&OJ8wg?anO3j4Pk){-kH=OJR zFMIO_z=FFEocs}$QZZ0)8haz+C^+yXdj!MDLTlR-AW2prfq=%#!kz3jo$L!brfv&e zCv-N-j31Cq9YRqWMAIA_M%?U+DpD}(RvU#LS0G_D8yO{BAS+NH>yb^*tO8lM!NrQ2 zk$doak_mUry($&9| zd)i^_9jklpEFFo~oHZUSXN*!*=QURYMNoparf^XOFgVvfY;`bu(1hQ^ufcrRchpoW zhG_p99x!`dU&YF$BsoazyroNTAv_=pT@`2dp7XB0%s2tR^%>4kF|sbL=#8?5qh;W?r*#Jat)j zVE)qFYo-XTTuP%LKTmzI*}>EywxH@~{Q95)NP}OLjacc11hDq_69bVa24*v3%aZpa zRO=^_WtWc&BeJg@K7y?t_EmL+ZAa2)2Ub7hHKflLP0E;CYh9QEs~H2U1$m>i<@2nD z$A^+#MK-#Z=WLzv#-W0ib&}WT&>=GpnA`PsnBfkKKg7G zviD9O!ou0zPX}OQ_)}S~CGq+EyRdH`0)SB^!-P-L0iAa>Z08y;{O24kEL{Q)QY-Ql2$fc7y;!2Tb~(ZQ)>1hPt> zcC19?Q~sOAx}t>)JO(1BG?7Nm83`Ib3_;Bl?_828pD zgMVyE)xw%2i9colOhpkaW1QrE?<%&^dO7Kv?Mn}BGDc43$InIV^QD=n%1{ssj4qmda~>OipSmlkMqv`b0ideSv8g{HBH^2AIo zfS4J`QF_iY62dNWgtfw+{oc%?g1HRa#0QVPBOy@FtN$jr8?@~+c+eB9xoy;2i@+E| zZ`}5~tNP9)yDYrEiITd1*}Oda;zMHqcNDgmwA1c6cw0JSfV-^&Mizc-K(@2N-dBqt zs7R8qnFBtjB%0PZ^eNxW=yA3u*zW$FfSv0Cl*68+>5;n9^Fsmn&F=`%0%?ZXxe2w= z0n2H~OD)Mr_vnsRAG}nN2!P9cX05^$X}bw~Ap}<14p9>Kw}yAf`#gcsC!mJK1(@F6 zX(GxA7iqgQVZTLm!G7^pv5_d#I{&erd|ze4Gri6g>vur#@eMBLkyq`a-t_lBRf0OO znr`p+iF+x<2OAVe>OVBlaNyPY88BJ*xa`78D{~d3{c3F;ay6;5FMi%VxdT)RYE;rh zLe>j}<)IymCY~Yp^p=Lw!t4mO;~-z>ktYX+R}2p_|C`|xM%_*7r;A^7-@gXtPc3m` zX)dokoUFAab@5gxN`6pR`<`!6wujD9{3ut1a9LTqJU^BgBr&wug+-T|b@9 zAypuB!+-xVxGp2o{)TH+{D)_5V6AyyRdYTFtSGBswHmeZc>pZ&U3JsGs#2X73pw`1 zXnUYIwzUt5Yn-j*+ZL*QNNGembW~UpVVu5FYC41^SJAR!^7y=AM4Fg&9 zIe)R872V}KuuFZd4e=PUVV9ElAz|JqcPQ-BK*fUUWchUPvAeXU_#vjiG!9;#hA_UQ z=WO|Vl?pj{qw4K~Vvb@-t?do54dKX>!0u;P>^{JDf3-+Z;ytWtr@hY-nC=H?-GlJL zuG%JkT8;LrGt%Rv##VGbLi23z0=}zyn$2-V@CMZd6BKE&j*-Mg{DK1Z4nc26J=G7ab?R;nT-r}h4cvC1^d4hG*T3B zqWFg2ZHja~SUcq_A*J)0K79sIQ_Q-bT}-O>7Kd}OTG_-(kdY^Fd%H~R)Ef+kMC3J) ze$zZpQ^-#f;cmHcU6tS9Ep!#$7Cq!6kh8Y;$9kPuib0elUc1R<)Ek6M?>&NDRO9Qf zu!LcAY|obje+v-dHB`^ia_OwtTO54Nt`g$HQeqZ)SaH0qU&`04T9>SA8+}T+~#d!gShFjqvFh(S6L#@)_nABi1-0l@_guu?O?>ywvS-H13 z^jh%*z56IlIxDZDxsd61Vpqb@JwkOK>$Nl!f^ccurIUTDjbAA}GJ58Hx#Ze7G3QM_ z?=24NuIYm6SamL}t?kv`p&(J!#BQe`iY?R+#&lo3O)mA7GoOTx5RkXYYn@}$ zOmP&Kx15yFNZZRCjEH8xiixXW$9VjJU)2+W2Zk%Svd<~E=W056I5hoR51{Z3PArS? z);7n7b1yez;!SJ(eH92@Wucd6krkGU7M#~Ida``}3iMSXbiK+=@2Y7LyGB33$VZNE z*nYY=hRa*2jNz;TaJ+073RjoteLjGPTgb1ZYc71sW?JVx`dKPo7H*dxGDD3RI@d1w3_!q}? zEBgYsw~jb*irK()^K6h+cr zqF#o7mPr_3!`QqI!%)Y8w<3@yH<)XxIFbusicnwM%P`EIn|!^xXmvsf3JZq&1DR>U zeQgplZs431K+d;#3tLxtU|uH-6Lf++s}lw|5~56S@p?zlJm~XNI(K5dszt!L2Q|5? z8nz0dYcye%5_eX^K(Mem+FWUqNwn7rW+L-9OoodUOk8MDOYch?r~~ba1m3jj8ytm0 za1>-@e9|(}(8@;Wb*|b~Ops|6%vYl9bDx^DRYiH^{$qjcZ1SE1#+rBg=OxZN(M4ZH zL&Qcj90F(vD-MqUXn5td%#9h%;`%GqeTfwbn0o|TnwGDGW7QJ`onu*jGkDWRgM*#l z^zoNK3j`cY3o3}yU3e3b*l^rANx{ta3b6Sou=%T1n=ky$<}<~S5neJQ1l)^Pa)(j&=tG*GN`<%D>) z_<4kva+yXLC}QH#YH8X7BIA$s_+Fd=9aG26mVhAB`jZv*ufpuKOI~EmK_|r6u#GK; zNjsgfk1_99q%clPJ*f5CdEdlYBL#bpMN%B^re`Zb#(B z(DJS25P9HT4}}ytU37jq+F9^xc|lKbrJ2^<;rZzoX>UI}I7jun^nzOIh`@4hIA$e8 zJRbrQSk!|9=IJ3dQgYt(jf68pd7qqn;fvsWxG1__H>73teBF`cFtC2OJA|s6u1~O% zk%k~wxx=|}4yp%bL0 zEVL6bA*kS&E|=Zc3D_hI;KlZGAG21jBnGzeg2UY=K+Z4;v>44omi$?da0lo3*)IRC z5-#u3_T)$Crzz=p5>rm?{y6!f-b=IRb7*sbFt8Q>5^OtbkVSSJWW}M z6K-vPfNLN?_X7mEM9oG+qO;=*Rtr?9W7WjRW$1u^H0%jV=^4|E@}tu6m>`}>uo@j!$Mj!{iK+JONFl-uC(R~ zV6)thwJQFFYiN>Vdrl!F?ZSg4Zo}lb-tfT%=KfSWQklFTRh0NB4O&5Nl5PsLtFt^! zhbMUcTZzX7Dic-f9Kv0a&f%8kwJCrvJs~Jkil@O<$Hd^fBqtYj0!j;8JPH}WoluqU z8K}Orc0`i&d?=`2Rsr14**DBJ~X?-;aloL5Lp zq~GsAw^jannlypvMGlkjiPU;l#Xly0YZvm}*L+Oz*NJmljYKA$b|F{^18c#=;SRw^ zXx7Lbt(Den^y7AP$1&>Kt(O4S?X0->zGm^~Lo2hNAJ%GI;_%vkto_bcM9Lz`))kb45A%cPI1IbMl#Z|zOZ zH0WRx9^<@`qu2B;j%VyU;-m&Hu{yHq^IsChE@1PIs%sn(C&42CXL}6lNzrBDJiY z&hhQ4@?uYDR&P`oV&G9^L4QhE+tv{?&r~Gp|J=?@)KTQh$1&U}gNq{LYPYepjp$ ztPf|h?5;8GjXvwJ-`DHOmE%k;W;MPtd8iz7|F`CQXNGtGP3w=*2s4Jb3&#XY-abN5 zUmrL}3~_A|a&5A$NvpkRaoIQZDay;?T&MoU;TGME3vNxbZ#$hd{H!|~5%;Y2Ijf-{ zaTmp_I3uh%BW3tkR>q?VSJ~fIMzaN79LhCEww(Tv5&Q0hV9um`-YP=ga^^c@M{eJu zd`?X;#C!Oyc?ox|Ewe?iOl&Xr77PB&VM4dy zF!?)uZ!>RM7Y}o$QYKax+I&mw-_z4gvoESNG|$S`D9K$~y*&c&rNTP_`W`qWha zQ%`iRDf6w!?UAP#q`~BW>5g}|nQv8af0bs~63!^1o*w+xzgF{@yx#+bZtgAXk=3`Q zOy->+<_`GfzgCu;yd~-L)_@-=@lS*^tpRduh?W2C!r9iion&yT-imy-UH-dpO1G`~ zRc_aYaQZ64;AF-;_M zhw_K@|Cw+ASpFXC|I39tm1~YT$zT_`UDk}b|NBr6cKvB1i1ytHz?=aw%=4YY{=p`- zx0(B&%EbOKC1k6&MxBB-|3Utj$;4_yoBtsHf&6wL{{eXX)BL9g01x?&=Ckc!^S|f+ z_bCSCuNB0cDf>~N{1fASj}!k5<6RulH~zd;fqVyKh0FKieP1nN$=tQVm@_|&z>X!9RoJBGO*U_1Foa0leapJD);|G>93GO_SJu=$UCE5k4aeEY-X z{wK!!2jBkKctNg`teAK2Wd69+cjxYR;$6)(f3%@%Fl9a<&9J9}`^2puh2D1ZowLuj z|Mb0YzZdV1uiPh&L7V>oqxM8@|H%y6{9l(SApg7A&s(?u$hScL15ahZ=07N9K>quu z7{KQL+PDA2cwx=o)$RX=@p_{DOSn(iG9L(*`J?AM@$^OxUf<9jg>6@<-Wq?3;o%R( z`y}&+PT!r!-}&|*#gk!p2z>jm+6p?X946nn{0!RsU&9KJ|AY|c-KQV<7RavxeEY+^ zeT;ec^7GciKlJT?ZM=Wz$$o4+P%^YnGF*(@&TqyX_I>F6L&*LN%WzZ<$Gg7gzID#F<^;q3?>cxO2)%SN6RO{@8&RZ)T7^Ai$1X-`0i;>cnPjH{3KNL8{r8ro=LB$Cj!G^0v9*L%h#v!CKb#pQMD=F zH#)y*z0KH*+f0p3U^%u4%bQhW_h!xA>{vEig3Xp-vnBYS;2H~n3Z2$!7IrR<{yP;y zu2Uf@phAV8Sg4;_sDKKY|D6iK*QwAFph993UJ8?5ctC}o{hbO0uTvpUz|{QYO={## zusw{fe`jh=8<<*0ALIWq@zA~ywf?V&?(4SGpH`XV%4H9r)|_U{7T=#{eSaXcrH|3| zDCFX>4aXhtfxEvQvCt&7nmOp+2ObA5=HGA=F{U1U;@drLQ56eS8S?%c;Bnw$#tj#s z1y2Mnu3ozgqbI%GA4A?B1|A14-f+pi6S!M@^}2U~C~sm+_x`4Mo7OAdjJ?g&*aVhM zSpNTa)mT=_8{sD4Sa&_|4@PyD40aU>VHF>bSN~}n$349=5sBM>1XsDW(+!&{8xHKhRWcJ@dwc-YWOW5 z;||DmWC$!G6gmSHI<=;}l&D^6&vZUs?bSbQUqAc1R+xEE<^{utQKKy^w6y54vgk1Z z`g$)e3Yos1c>P$`((Spx=L|K27b2zAGsBFYaIM*ETC*(BdL~!+*-q*?H(iJlSFB^{ zYdIoP&wh>UO7$vA5m-zYSbPAjcS118_dtrg)eB8dAmgO<6Lw3#^hpKR;*Lg0E!ywU zdSOr1lppFwOI#7~2QoTKs`+J>G|xpVbdC-}YI#0~*1K5o;NUcpXZJKE_nl_W}e;+nAr$xU>7qEUVV7(E+P1bNX0HCGAw3okv2|)gh zV7Yg_5)8Mn;8LIkBKjG*T#MJ?J8TVfuhm4qK|l*M|E|@%v7mfdD+4?LyeWgw0{kw; zr5mvu{Je^|%^3pLaA*O^Iu^-|)#Sul4JeCNFac$$H2Td0NV9d|{&T%5QHL3cjnD$H zDM+*RQgU&v0Hm91{ku%lF}-hgoNtU}`3~Rm*4VY$w#b#=v1hdcDw!|4W(@I-bt`=p zplwy6Z9lVKC#9(5s@Z*8==H6pWx0KLp5e`=!&Ynmf5c&%vAo_BZKnAq0&W%uI?vd| zn*X6cWOkkF%udO**kjr&O2LFf!Nh#S zG1y-4^XeJjVham31zI4#pHXfjv&&gycHMy48AA&+D{D2kY&a_Xp#1HCkH?ehwKNDV zAnHxZ#JU;#zu5Aq5dx=l(dmT=ey`z`=N2eM;y+sQ5?pa=vz51#dj4te}%>kH0a(M zZ({+UaJV(?wcWKC%md^4t=*0_#w8%{THHCv$UybF-w%!JpWfKDMk6(ys9ql$S(t|z z8S0>M{bL|MuU+j$jSVyUqzG^~voJr0#`VvW9R6#Kx^=d&FvGQ^-w1I34vp*dPG$cZ zA1%%h;7*Ia^@o=9U(mSjbbp}eDwFgw*ZQ{^Xe^(88|TplUCnJ-|DcHHwV8;{)sK^q zhdt2_OWQpb85Tb(eJ%6ca%}BGC(EU@f`j1B5BjjkqRc`^1Y&v1|5;mZ2HR#fZo<{- zC(ZsdaJ89Yn<=)LVw))z^gq}#ZDPGD!z2f_!ahwtWP&4XM!iDf$*GG;ZLvm)Cgh1HfwwT#6qnbb@)0H}cx& z>%2Bbq0?#F>#%Dvmf`DKl^)n^Dqg4;GzE$Ii) zxPi7ES)*+)0Br+b@ctNm>lbL;K-<*TXqy_KZFw%m4-`7VyayX;+mkig76h&%?WVn0 zT#LaxFs{?KBkQycd>3(GkWql@71R%n>%8{DI;E|d>_<31SkF1nBs%$Lb!>CX1p#_ z81K(`JsyU}gZ2;Sdz#;+Kd$>|q4HMXbGmn3g@r}{<&kUgORCp<*WwHG@u94WyRG%t z=1&%;;)h#U`kIR^%rcLbIebzu(Qz&Qs$g=2KC1A57qRP{GY_$$FMxSufI#3RcVVBEZ zY6a}&<~j&_cmu4@ZFnH{A+D#HIalD}O|1h30zfS=etvoFi$K{=0sas9RZfHT14JI` zsTkT?`?RsBWC`qPX8~$~@y3^vgF)A}m#L_*#2*Cfm$9n|$BW3|&W|w0x3c^+$_Uf~ zx0c%=xVvOLwx1 zJaTiFW8_=^z>+(rMls+Jq$mud|b%mZ&Mm&dz1xugy)k;;q};YA*|-Q8!Vo)88| z4JjV3p9<&Z86+8>lFtZltHOLewvB@MdSqJ}`JMg_&6>M@yCP$@@4s7#`MMAobY!bm z*ai8eCh~>LKVutoV*0$pZ+c+`;c=wo|@xmSF)&Wn~~b<@?{ve!#c$6{(bn z>e1Sc&b~~MY`2MTMM3YZ{CV7gtI?*Lf}_8qo1dCZeC1$>&eo;i#^d#}h%Wi5i9T9)gCgVrljP`2w8N_1E1y_+*Vl<1!Po%C0oS6@wm zUe(WXr8?BSB4uQ|>QSQcq>P(0!<1;sEy_!;_68EkuP%$7`#viqT)aOhFcq z{BF*4QIIeG^BL1a=So?@_mg|G;yjLW@Y}d!54tNCgOHrNtF^9NT z?`)<<(E{+BPRh9~CN#$@gj4<{N-@#xy;%&8zEI|E~S&w;yTV z-jytUAw}9tkNX9j``mHn`s2)T>tzMdPJNT1jP>PObzR^)kYoAb5gCd+UN;2<~Y=b7p74!PR*E;pbx%Q=>wsc^> zXaJt#1*dHkz?tDX7mp&V!#+bB=bgHO8CvY)Xk~tGMNz zCOtmp^3wC$U$NZT8uZ7i@n!Bm7o=hl=fxjYdu}(( zAkLdTeCnK>9^WT0aW5<{&YL?t^E{J+_<#@lJ&XGNBCK^U4jWu}uBMS$`+HEd#UWpQ zSlu}`Sl)B*L$1gtaDm+k{WS&QI_3v*vDuAD@>CnSG)xYtBeMUN55| zZT`4gzgWi4uKJg1{TG;!Th+fsWq4uO2O^I~W?Ud2?~MHRYGvHKfrcdS#$|*9r1INq3mj18ZiN0q+sMZN7dTjPGh>H!LZA8De`jJn=M-`op)}zq_KSm>y}-+ zc5M;nDA(Jv;lIP+*~wbW5p8RQu`n~U!-yH%nptDS=s%nkbwXK-LO(Ym5NKla&r3U( z_T9a^jk4X@d}KyMQeT|7_sy9GpBqe5sIwZGFxBTfF3*k8=BwE#AAQ5p%AU)ddgRj_ zfDIJ*kZXRUdXMMq_@wQ4*ERe=xbDKl9t~;N%h?%?1(ssQ(Mx24l(M{Q9V*2EDWZp3 znix(TsrGQ2PU52>#9oQGYdJQ)&gZbZ@c;Go6+m%r%hrRtI|O%kC&4YaySokUHW1w1 zB@o=*-Q9w_y95XX3%ul<|GsnX`QN=gRa0YoRefuB_wMOlHM7@>eO#)LR%Y zqt`fVE3DS7;2O7+WMNea9Fo_KkVjm>9cT-EKGy;MFY2jsUo(G1uCQ6 z|ILk)nnuunb1}0?JFC=aCXGTd6LjizM+!l|RDW9}28siCELWzm@Z^h}x#lGnp>TdS z%a;I~H`QMt<-5P7G6UaZD-dGmjqVlNe<1BgLG5v?k_>BJ~7L5wnnm+aSje%n?b~Qy%eU z{szv1lCTAXeI2$GQy_38QY9$%+HsBIPQb5|NbY(H=PC^o`wMKY2wQC%Q+2Zo_Z({} zq+C|S1p~TzsOh|Cz4hwrck{*4Tf0w|X|yOqw8jsKL89adKhjE8t)GolJ}JbU&`FSS zexL#ogxeau1;&aS3dV_e21ddIjCX8j4ix;~G^Vh6AlOCO$;88|h2QC-!5_79<$~YM zMDwCT3u+Bh1WS;Z3WItXVibo=e?9`kTA7)FpT!*L5MPQp*aBo&278f=NmO2X%QTwOuyqx%WpD3XLx z@7*6GXx~xY;;{G^q5xJNGa;Lw5`=^x?d^oz$l2k{K8Q|~E##~PqPB9lPsty*X99JY z+jaDEz8oc=u}eqb<+vZ%@(WTQ<3Azua92c4|*(`Ffs~vhSovXgq$r%4=pRXVrK{Ieqp@P!)#rerZCPBq-b_YszpwpfxK$115FVH^Cn?8%J_lmFfYGbH} z&y^b=RB351!EHHBlAf;4nwaNsZ%c1vI~&+&X;A1wLR4avb#xP6`iV0fH+kwvHhuv zH1p_-ZE;FEZ%o%*`0Aa>D)X zY?FrVTm8{?QjXTxS71wzxWGHbJ3i$0L?=V=`-us-3B)IGq~=m8Hg4agDusOt{1GJ) zn&o_{()ZAk5UJ_GgkUW%6;x18{eCRs=o7fN<{-^9%&d=NbTu(sHz{fNTvP#V`pmR+ z60q@hz(;I_&EkGp≪DWar{u2bkUtA(C}_&Ig9WZFB2aRW?qW7JP1I6CV_ z_vYU0>_p7O9gpb{^2$! zTNwp2*9pORr1Kwty>2DBvGrNjbP;p}&)1=OcH?&~33Kl=L1A!BhuQ zNV?L;37GHU4)wZz%W$PP%4nAb4H*8-LR)s6xJdP)y94D^%`=sUWtUm=mt(S$fmbK6 zmMRX((&z^{YglVI&FpDfQ{xRyQiQj!HiAyk@GUmCicD%XL#-X#c=cnmnwKdS)C-8T>4~A`&xL{jv-dA(^bptCsG#=(}Vp?F^ae(Zq{5DLv*~Ta*{!ln?u@fNMPSz^OfcV(^nxZ@8y&(y2~Vye<}HPOuPB ztlk1OA<3j*Bz&Is8b$;QxdS|C3;?H+XaL zQ%PCJEqLP|x_D6On8;(jS@R~xg;^(QPNV9A`Pu~bop85ZY7`Ylgu?okSsC9fW_P6Q z&%u&AGD(@cuF@%__Bb%I##v^OItJ~Xs$4?%ivu4OU$W{4_!fq%4?hkfHRo!#hRGGr z8)kV)h+pk**ze6`L=4W1L>VU6E>UVQ@S+~-6R~h>MB}RUtPl+ zz7rLqu#DAiLuKpflL&kx&OUHCK+LM<5t-E$YmxYi7E#LbV+<8f zmQkn2JWMC`#(J->@t-XB-m~AzQP1#te#f;>Knsb5)GyHUIA-m+bB^E0-0J|MigSg= z3Tv5ein2g|JId%C?Km_=+@5aiAiF`%cjTjCyE4b?Kb+N=)D5z z5Cb)|t%+MBtsA7sectT{I+}%MWd#dq(xl1CC@kg@y4)^zA5l;NE+YsT=SGOfXgdzZ z9==m#zg$(o%<&%>G1y5>)qRQtbYGl_-dbmBFk3Tp-cr^6)ZHdprF1-+w61OIAU)Hm zIZxgA*l==X$Q+*!p*cCk(2vsChZ{zuO?<+8_uwxewlTcX`9%D?EG-pjhme2=01z_( z|D`O&__Hi^u{5(YWB%j*k6Lt6V-2`Yg8DP?6=Juucd3)MU8ycpjaXalwCR++_PVfl z8Jx@NwF}qV&POKSoZQR+e2+bpoxLY+yu2F^3MD9#!@|bWKob=ed*5hmm-FS$`OOn7 zATBL9?J%lh2LtV!_3a6IwW$ajcoIJbeMd-m(jYu38Vx%(j;CIQ zmYqbri57d(PEzk`ZugL2Y(57`y8w@Q&}c*uMnqu(Q$hnODoYk^bZ8JN?e-zXO-jO? zXi^C1M)Y$sO3hBE-Yc3w*P1di5sRLv%p1w7Za%co0c!J7H@*f$pZ5{vhvHp=T`wPe z&?g~rR^2sc?AOimTIdpd|45Sg>h1Dl@ex+k%WrJ8Sve+o;J|i#v5~KVP zvro)_Sk;hwg{ui8J4k<$}l))t70ge zywh31yLx+154y9Hby^q(o%RE6w`375EsNXxIIizr*a#}1YH0)JKFtdHK0-8BcLVCa zrl~?>-h5*t!D4VcH6<9R?K+zW{X*C<>0)Sb z`$2`-W%gL3$4lIS`yl@3gH1={QpQ+CBVZs-EjquI92VNp44V&VOcf$A zjtAfQq?-oynT6Yk?HZPO0=yNVwQYom3KFuw!M z>`QV(VkgEZoKX&o^FS|V%MKB2#rE^<+njE6CXn?WCSc`{@aO6$e+99 zMtyCtW&;^jU$;}D>)^+WePZ1;4|N}tlGhF1oR?GHH1$7x=^9}~Kz184BVgLPYJTQk zUxL7uA4-0lv@m`qn7pLoaO^>Z^hX z7@Nk&EX0gRB0`2D+vw1Qv1G~6v~2W43u>__rsmC2%;{r}S&&0>k_)6$T_N=j-3h+w z35O;liek>6RX?U&^#@ddmaC4?yv@CVZ{#Cl9j^%lD4`T?cHAHP(*(vV$Lr1X_Pc>7 z&vH%p=YVWz07FfR-_MPB@sL`(_>qs)#1&f9;c0AdE$d9&k_6c}FD6>BnqZ07VY)QW zo6*AE!j{v@&6(c_QkBKP0u*qI=b`O%YHiSleH}VkZZ=3R7|S2`&=;``&0L6vp-6w? zJ@HiLA%D|2jc zptdONJT~6x^bZulHTGtg-XgGpH`XseYKgIZJWGD15Qhz92+N3~;DUS4Exo~GN*`UE z10^&0^f1aPl1}v@jQd`SEt(kcAb{R-63Ws=Ed(AHWG|XXY8jEwEu^w7zgHt7lw0JG z#_oTP zBqZ1E7ikngsT*>W>I==7k6vq-0IKQ?U!aJ)K!h|@Yxm_!L=*???(Ayr%lS1m{c$yp zGYJiZu!t94$W#=?Wg2g%Yeb;@J1SK7QVTSy1dYIevJ70CkVbF)(yPXNRSt~G8BB-t zrOyQX!%4|OCSwk#JQGURQkOWZnIM$~qy`Ck@USpM7pyc2tC5Dan7*J8#gn5Hb41Oo z__%O?4+*Tp3TCQBJOoq!5`_Fbay&thvzxaYe%}t?M!HyT4wT>R5WA&msQp@6u6}`>Qz!6Ck(EQm3}szLy8O0(4kV_1_^KYJ(SS1#B`PtQZcF6 zo>RenJww1d$A_s>Q8&%skvs*>3V^B$ZPPb{T0=PGz%VG`P^k)x)|B-3%v>`XbgNOK zAn2kx3`KyUL~;S2w4~8jxAmAPIP-=Ddf;ujFX0~sKWz01n|}8xTE>9-Lao2n55`i7 zY9`*N55RY$=|Q)=?~N$sEI8K%_N8snV!dncr7w-5i42Ka=d0`8GYD5`bn4pw=Awv9 zfy)ps4&=BCxQ_1caRSj%UP|@}5c-fELwyRSNpFLGC_q2lfOKTz^GieZ*QPH+UvZuT zv#LCjztYQf>%(ZsGK_oMg_ku91%tA%h^_S5%xSsz#T0Qdk_J9(4`u&6GUipHkcv=8 zT-**qli{3`9?Y*aAZ@13sKQMH0c=}yMRM!N)X@W2Y!JR%RN*|`m1WoQC@DWww|4|} zmqJJ@yCC5_D|;BjyP-({XIL+D_9^Quq1X~B2_dxk?)uXn=3_*;K{L3}46$Cd5oHM; zbqM8|M!G4sX|3b%L-{ya?NdSN(PDRP92che(R7K9RmWf~AjrL#ee4)k1Hn4cuya%z zi|dVfeDI>xR9Uzn?wq1V#ZZp#2KKIOQ}yY6MUIR-_yU@v(#9VMhr3fE%J}$<+EboF zRid|5e@G?8+@Yv%LHXLyC zcwLau6g1dE$RL+O;yk!d7${U2($SkGbk7QLp<-VEJQp!K|D(t834x zBsg@C_50I#q5)7Q5kjZ*{;G?MESgs`y|^4Ehjbrh48Z~_PZ@io-u$Jh6+$_*8XIm1 zvF>3goT+2=0auZ!F@rpap0WucL!dY$+(u*FMbL>TfWdhQ}NiKiIh_}X`GD00dCTrncj3|Hw;x zoIph?R2PESMej~J-7#`6;!yDlJ@&+cPEJE7u}IbVo_ntKYWxPyWzhG7?O}J3YD!%Q zYKL#G`T=gu9OQ^Uq7@Z?-kE!G!Z2#%ChKBf1Z*IDxVAs?Y>1@fmd*>S2U2E>5c{F| zz|V)QN&}a1e!?a+tBi@1lU<}A9yHSn-w5Woqr*G7GFxdu4z}72B2P$(piOSqP4*7AfV19!o?Q0%R5jeWbr|f7)qpp zLA*+z*cbLNlZ#1GdC2ayiljcl5h~YY0kz}JRJH@kCU4&Z8fZo{Kx{kpJ5e-2U%o0d zUTAnMbaPL(g=DNkz0NvHHrxla1J><_FKi&pVqb@ z2E?Kpi*MMfC1d3*@Ms3(oMYa6K%$71pQCd9VR8yB&%RI6YCx|cI#K2HG&az*b>rKl z?Fjn%s}vE0;A$R;eDrHI@fVbbnha3%89l50yy5o@EA_TV<+22yIk7FUiInap&Me9v zpR9e4nST_Xd0#TEs{GWZ1Ho>LiBX$hUkc5iG?l@j7x~nV#qRs+4jaZ+Wg(7wWwK;E z_{qd8undtq5K+gzasA~3jhihx{T9mM8fWfBZ;Lwb$7hQ8nt1GNpR4Xjf_wjV;5;gv zX`(*|l->dbhaj#egFRoOr=TadR%De_+E^|uTF^q7kamEU0RzM#;3g?e--9qP$e%g9XA2e5C6fF3#MOIn_mSiM_yfs{ z$}CH4m0Z4a5OM(+V`!L4`(?_;>9mGZ;Mx#o6G{N=MqG?!e^aIVdBl)WT2}!D!?Wo1 z=~1xI;)@7fIQ3qXW0`JujmZY06#&IX?wCC(qcJ8EVpYiw`Xu@P*K3w z`qpR;T(ofrM2ePzSpyzE*y01s;-uA211y(Xp8U-H5o~opyvdmu15eLbz>c)q3)LeOAPv6t%xn$SOR1=;^DuMy zoAND+L;kqZTFS-e1eZCZawOMxDJh_|o3FZ&pmGDw0}5BA-b_kF;-Up}q7OEsGQ)?B@ilb0KT1Z9iXh0_1`M1usZf`~uAt?Tw`b6#&k%Yu23MAp7pd zWmDs$WOQMeC+Q&nJ*X;~fMKCoHIb4tKnlt3P&M%o3H=auIrz3SH`vB7Zp^Sg(V4-m zO$P9_YFh&>)abaC+aSN8ms}o?TeMVS4F)$F`qR9M`nwso6p|qa(@73i(bAZoaj-i z0ZuH0a4P1?fc@|n3!CWa4+J`Rk)udIfEs5j0!<&$317v7YfFCslpy<(-$y610Ivp{ z9hSZ>GoQh6n?AUmYQcxUtM#tGrB3!%oBK8UHc83LEXVvY_TO+c?JHnH zYeWU>cE>6iV*O6lY51|eVFla`t>`wHZgY0h#x31ScM)9`N_AKsqdH?v0^a7tg0hSp z3GxU1%;URHGMz>=srF{FD!Qnsv5X*X z@R(1o*W*x^gH>I6`m4k(V9G9*-EcZUauZFDoK&U~RcB>2J0o4B>?-V;TRePye_zpD zZlVba61N+%Mrl7?I^E}<0V8`HFk{Y9g03Tiy3G_qj6}gRzLr zH8nMkBmVg6|GRILeMk*`j|KqTNd33I5z_zb8@YJen*Gr*I?%9FSYttbg?dIw=~gK& zG=`uQR!p%nScc)VGT0cfVt7I4Ws-Tk<6o0Au*B1fN5v?`TysAK} zS~po2IwE^deQTO=n`*n~#4Sf=V73rh=Z!Krknd`ugy&+?*r|7$J#MR^EWf16HWE71 zW~e4f`B(?Q5KBiUmo#0|bLhHocgfmoIv*v8wkj68gaw(LhB_Zmb0_bd`jxQ*f8xe) zjytFBv)fgs;Qr)l$f;W_-!NXS!`UG9ds_KH^-iK0f!BoU)?)Chnd<5{$r?8SXH=F? zKT_P{&c2yd`HFZ~eoE~QezJ^tzw3E^PdsV$y>{s{?f}B+uPgxZk1*y$jJAzpoS>) z5RzT#43~W7vYtZ{arva#1E%Xer+H0Yw-HAaTJOMGWQ7jb7OwfoyX8~&c2UL7XVnXH zU@O1OMhU06Q&2aY<X=D}BU#CAt?dt_UXf<-|ARgK~c|rH07i5sR)C9hicA7UHr;u*Zx*zHf;t zhD62*&_M$3Dv*9pnTI`YMo94(^1H~Hfr!KeE8F@~v3bAR$inoxuNdC;pTx{nju2Yd`)FELA25TmRY= zafKQFu$85{MCFg+S#mU{Yeg`qbIWYCl%#U2Pxske+kB`ZIQrplgD-D0mi0gJy{-dj z-FxXvBG4hdFl>)>psqqwpQ%yP8=Bith_Is4jC8i_^lO&}*jHRx5s~q#mCg4Y zW?Es<-fwY`B4ub6sY}?!w28OUjZ3B<;wc)KMs%vh-8X?d;*!5o^K-~qIN(fJ2`OmM zQCu@PeU@iT2sH5IDi7=z(znoL9F4O&e?+1VtM5|l)^FH63A&F)XZDb1ZMN?fV1T>D zn`7k{dxA)>AXfcQG&mATtlx1OO?EKG)DPuL_+_0#L3VS z>!cSSZ0Ww^Jpe&Tn~}PX#&8he+DOaHGnxhz5p3x}H~s|rAmP3*P(oyZ$L3`DwTN7B zJWayBCDA$w`jKh+$9gw`qHkKoEV$1X1jCEdZ^W5xKt&HS*WB45Vl0Dj3K@GAculHT z3c<~=A%?u3@&tbY&CWl-7_Vs$>g8OzIA6VJ>aA`4CFA+JZ=I%-XU*_pLZYC+dTpOV0RYi*s&aXOt zlx8Khv_`G3Kj11*BNG!R`x$}EVS^)*z! z#%zjo5<+Zvl=5uaJF-96eS|le-5=py!YRnF!?K(=1v%>NV$wIHhVOLz(qg*n57zC% z8WcHyF^&iMn{_a7Ou%1qLKtJKPf)+!gZUM%xW9P+cl#wSG<7m^|2ocva60i0RK6n z{wKiS%ckg#RtV{<-w;ne_L`^_PV${4X8< z%A5aO{P(2tJK6qa=u3Yr{tv15pE!Sy*xxDWFB4n-w}kZ1g@1Rtf9IZg<^K$CMHwjQ S-{|naZW+H)Vd3iUXa565V0&!< diff --git a/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/citation.bib b/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/citation.bib new file mode 100644 index 0000000..595a916 --- /dev/null +++ b/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/citation.bib @@ -0,0 +1,8 @@ +@article{bbm-233, + author = {Taoma, Kittisak and Ruengjitchatchawalya, Marasri and Liangruksa, Monrudee and Laomettachit, Teeraphan}, + year = {2024}, + doi = {https://doi.org/10.1371/journal.pone.0298788}, + title = {Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy}, + publisher = {PLOS ONE} +} + diff --git a/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/metadata.json b/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/metadata.json new file mode 100644 index 0000000..04aab91 --- /dev/null +++ b/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/metadata.json @@ -0,0 +1,7 @@ +{ + "id": 233, + "name": "BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE", + "url-publication": "https://doi.org/10.1371/journal.pone.0298788", + "url-model": "https://github.com/Ktaoma/BoolSyn", + "keywords": ["source (?)","curated (?)","repaired (?)", "multi-valued (?)"] +} diff --git a/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/notes.md b/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/notes.md new file mode 100644 index 0000000..ba2e26e --- /dev/null +++ b/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/notes.md @@ -0,0 +1,11 @@ +### Modifications + +Removed regulations: +WNT1, WNT1 +PG, PG +NRG1, NRG1 +INS, INS +IGF1, IGF1 +ES, ES +EGF, EGF +DLL_i, DLL_i diff --git a/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/source.bnet b/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/source.bnet new file mode 100644 index 0000000..57db0a2 --- /dev/null +++ b/sources/233_BREAST-CANCER-SIGNALLING-PATHWAYS-T47D-COMPLETE/source.bnet @@ -0,0 +1,110 @@ +IL6, IL1B & IL6 +IL6R, IL6 | STAT3 +JAK2, (IL6R & ABL1 & IL8) & IRS1 +STAT5, JAK2 +IL8, STAT5 +PIM, NFKB1 +STAT3, (IL1B & MAPK8) | JAK2 | SRC +STAT1, JAK2 & SRC & EGFR +GATA3, !STAT1 +PPARG, !GATA3 & CEBPB +FZD3, WNT1 +DVL1, FZD3 & !YAP1 +AXIN1, !DVL1 & GSK3B +APC, AXIN1 +DC, APC & GSK3B +CTNNB1, !DC & WNT1 +TCF4, CTNNB1 & JUN +PAK1, TCF4 | RAC1 | PDPK1 +NOTCH1, DLL_i & CTNNB1 & LCK +NFKB1, NOTCH1 +RELA, NFKB1 | PIM +JUN, (RELA & MAPK8 & PPARG) & ERK_i +NCID, NOTCH1 +HES1, NCID +HEY1, NCID +MYOD1, !(HES1 | NF2) +MYOG, !HEY1 | MYOD1 +PAX7, !MYOG +KMT2D, PAX7 | !AKT_i +IGF1R, IGF1 | (FOXO3 & ESR1) +HER3, NRG1 | HER2 +HER2, HER3 | (FOXO3 & ESR1) +PGR, PG | !(ESR1 & ERK_i) +ESR1, ES | AKT_i | (FOXO3 & (KMT2D & PGR)) +EGFR, (EGF & RELA & (HER2 & HER3)) & !MEK_i +GRB2, (IRS1 & SRC) & (EGFR & HER2) +SOS1, GRB2 +HRAS, (SOS1 & PIP3) | !NF1 +RAS_i, SOS1 & PIP3 +RAF1, (HRAS | RAS_i) +MEK_i, RAF1 +ERK_i, MEK_i +LCK, ERK_i | !AKT_i +TWIST1, ERK_i +NF1, !TWIST1 +PI3K_c, (EGFR | ESR1) | (IRS1 & IGF1R) +PTEN, S6K1 | !SRC +PIP3, PI3K_c | !PTEN +PDPK1, PIP3 | IGF1R +MTORC2_c, PIP3 | !S6K1 +AKT_i, ((MTORC2_c | PDPK1) & PIP3) & (IRS1 | (IGF1R | (EGFR & EGF))) +FOXO3, !AKT_i +FOXO1, !(SGK1 | AKT_i) +CREB1, AKT_i & SGK1 +GSK3B, !(AKT_i | ERK_i) +TSC2, !(AKT_i & ERK_i) | (PRKAA2 | GSK3B) +RHEB, !TSC2 +MTORC1_c, (RHEB | PIM) | (NRG1 | IGF1) +S6K1, MTORC1_c & ERK_i +IRS1, !S6K1 & (INSR & IGF1R) +SGK1, (MTORC2_c & MTORC1_c) & PDPK1 +NEDD4L, !SGK1 +NF2, NEDD4L +LATS1, NF2 | LCK +YAP1, !LATS1 | ABL1 +TEAD1, YAP1 +IVEBP1, !MTORC1_c +EIF4E, !IVEBP1 +MYC, (((CTNNB1 | PIM | ERK_i) & !GSK3B) | ((STAT3 & JAK2) | (ESR1 & KMT2D & FOXO3 ) | (ERK_i & (IGF1 | NRG1)) | EIF4E)) +P21, !(ERK_i | AKT_i | MYC) +CYCLIN_D_c, ((TCF4 | TEAD1) & !(GSK3B | (CDKN2A & P21))) | ((ESR1 & KMT2D & FOXO3) | (MYC & EIF4E) | (MYC & ERK_i & (IGF1 | NRG1))) +PRB, !CYCLIN_D_c +E2F1, !PRB +P53, !MDM2 +MDM2, P53 | AKT_i +MCL1, !GSK3B & ERK_i +BAD, !( PAK1 | AKT_i | ERK_i | PIM) +BCL2, !(BAD | BIM) & (CREB1 & ERK_i) +BCLXL, !(BAD | BIM) & CREB1 +BIM, !(BCL2 | BCLXL) & (FOXO3 & FOXO1) +BID, CASP8 +BAK1, ((BIM & P53) | BID) & !MCL1 +BAX, ((BIM & P53) | BID) & !MCL1 +CYCS, BAK1 & BAX +CASP9, ((CASP8 & CYCS) | CASP3) & !(AKT_i & ERK_i) +CASP3, CASP9 & CASP8 +HSP90AA1, !PDPK1 | ESR1 +NOS3, HSP90AA1 & AKT_i +IL1B, NOS3 & RELA +STK11, !ERK_i & FOXO3 +PRKAA2, STK11 +PAK2, RAC1 | SRC +KRT14, PAK2 & EGFR +TRADD, !KRT14 +FASLG, FASLG & P53 & FOXO3 +FAS, (FASLG | P53) | !AKT_i +FADD, TRADD & FAS +CASP8, FADD & !(ERK_i | SRC) +PRKACA, AKT_i & WNT1 +SRC, PRKACA +ABL1, GRB2 +ABL2, ABL1 +CEBPB, ABL2 +CDKN2A, !(MYC | SRC) & CASP3 +INSR, INS & FOXO3 +GRB7, INSR | !PRKACA +RND1, GRB7 | DVL1 +RAC1, (PI3K_c & DVL1) & !AKT_i +MAPK8, RAC1 & RND1 + From c07ce4843a58a4645359bdd1e696e44d1f311a76 Mon Sep 17 00:00:00 2001 From: Natalia Florekova Date: Tue, 17 Sep 2024 10:26:22 +0200 Subject: [PATCH 2/6] Added model 231 - breast cancer signaling pathways --- .gitignore | 4 +- bnet_to_aeon.py | 2 +- .../README.md | 37 ++ .../metadata.json | 17 + .../model.aeon | 378 ++++++++++++++++++ .../model.bnet | 111 +++++ .../model.sbml | 1 + .../citation.bib | 8 + .../metadata.json | 7 + .../notes.md | 11 + .../source.bnet | 111 +++++ 11 files changed, 685 insertions(+), 2 deletions(-) create mode 100644 models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/README.md create mode 100644 models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/metadata.json create mode 100644 models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.aeon create mode 100644 models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.bnet create mode 100644 models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.sbml create mode 100644 sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/citation.bib create mode 100644 sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/metadata.json create mode 100644 sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/notes.md create mode 100644 sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/source.bnet diff --git a/.gitignore b/.gitignore index 782cf30..ab6775e 100644 --- a/.gitignore +++ b/.gitignore @@ -6,4 +6,6 @@ __pycache__ # Default output of the bundle.py script bbm-edition -edition-* \ No newline at end of file +edition-* + +venv \ No newline at end of file diff --git a/bnet_to_aeon.py b/bnet_to_aeon.py index 1b0fea6..d27f728 100644 --- a/bnet_to_aeon.py +++ b/bnet_to_aeon.py @@ -2,4 +2,4 @@ import sys bn = BooleanNetwork.from_file(sys.argv[1]) -print(bn.to_aeon()) \ No newline at end of file +print(bn.to_aeon()) diff --git a/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/README.md b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/README.md new file mode 100644 index 0000000..354d8b4 --- /dev/null +++ b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/README.md @@ -0,0 +1,37 @@ +# \[231\] BREAST-CANCER-SIGNALLING-PATHWAYS + + - Variables: 110 + - Inputs: 7 + - Regulations: 268 + - Publication: https://doi.org/10.1371/journal.pone.0298788 + - Source: https://github.com/Ktaoma/BoolSyn + - Keywords: source (?), curated (?), repaired (?), multi-valued (?) + + +### Modifications + +Rows deleted from the model: + +DLL_i, DLL_i +IGF1, IGF1 +NRG1, NRG1 +PG, PG +ES, ES +EGF, EGF +INS, INS + + +### Model citation + +``` +@article{bbm-231, + author = {Taoma, Kittisak and Ruengjitchatchawalya, Marasri and Liangruksa, Monrudee and Laomettachit, Teeraphan}, + year = {2024}, + doi = {https://doi.org/10.1371/journal.pone.0298788}, + title = {Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy}, + publisher = {PLOS ONE} +} + + +``` + diff --git a/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/metadata.json b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/metadata.json new file mode 100644 index 0000000..c2f0b0a --- /dev/null +++ b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/metadata.json @@ -0,0 +1,17 @@ +{ + "id": 231, + "name": "BREAST-CANCER-SIGNALLING-PATHWAYS", + "url-publication": "https://doi.org/10.1371/journal.pone.0298788", + "url-model": "https://github.com/Ktaoma/BoolSyn", + "keywords": [ + "source (?)", + "curated (?)", + "repaired (?)", + "multi-valued (?)" + ], + "variables": 110, + "inputs": 7, + "regulations": 268, + "notes": "### Modifications\n\nRows deleted from the model:\n\nDLL_i, DLL_i\nIGF1, IGF1\nNRG1, NRG1\nPG, PG\nES, ES\nEGF, EGF\nINS, INS\n", + "bib": "@article{bbm-231,\n\tauthor = {Taoma, Kittisak and Ruengjitchatchawalya, Marasri and Liangruksa, Monrudee and Laomettachit, Teeraphan},\n\tyear = {2024},\n\tdoi = {https://doi.org/10.1371/journal.pone.0298788},\n\ttitle = {Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy},\n\tpublisher = {PLOS ONE}\n}\n\n" +} \ No newline at end of file diff --git a/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.aeon b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.aeon new file mode 100644 index 0000000..f8d3389 --- /dev/null +++ b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.aeon @@ -0,0 +1,378 @@ +v_GRB2 -? v_ABL1 +v_SRC -? v_ABL1 +v_ABL1 -? v_ABL2 +v_IGF1 -? v_AKT_i +v_IGF1R -? v_AKT_i +v_IRS1 -? v_AKT_i +v_MTORC2_c -? v_AKT_i +v_NRG1 -? v_AKT_i +v_PDPK1 -? v_AKT_i +v_PIP3 -? v_AKT_i +v_AXIN1 -? v_APC +v_DVL1 -? v_AXIN1 +v_GSK3B -? v_AXIN1 +v_AKT_i -? v_BAD +v_ERK_i -? v_BAD +v_PAK1 -? v_BAD +v_PIM -? v_BAD +v_BID -? v_BAK1 +v_BIM -? v_BAK1 +v_MCL1 -? v_BAK1 +v_P53 -? v_BAK1 +v_BID -? v_BAX +v_BIM -? v_BAX +v_MCL1 -? v_BAX +v_P53 -? v_BAX +v_BAD -? v_BCL2 +v_BIM -? v_BCL2 +v_CREB1 -? v_BCL2 +v_ERK_i -? v_BCL2 +v_BAD -? v_BCLXL +v_BIM -? v_BCLXL +v_CREB1 -? v_BCLXL +v_CASP8 -? v_BID +v_BCL2 -? v_BIM +v_BCLXL -? v_BIM +v_FOXO1 -? v_BIM +v_FOXO3 -? v_BIM +v_CASP9 -? v_CASP3 +v_ERK_i -? v_CASP8 +v_FADD -? v_CASP8 +v_NF1 -? v_CASP8 +v_SRC -? v_CASP8 +v_AKT_i -? v_CASP9 +v_BCLXL -? v_CASP9 +v_CASP3 -? v_CASP9 +v_CASP8 -? v_CASP9 +v_CYCS -? v_CASP9 +v_ERK_i -? v_CASP9 +v_PRKACA -? v_CASP9 +v_CASP3 -? v_CDKN2A +v_MYC -? v_CDKN2A +v_SRC -? v_CDKN2A +v_ABL2 -? v_CEBPB +v_CREB1 -? v_CEBPB +v_AKT_i -? v_CREB1 +v_PTEN -? v_CREB1 +v_DC -? v_CTNNB1 +v_SRC -? v_CTNNB1 +v_WNT1 -? v_CTNNB1 +v_YAP1 -? v_CTNNB1 +v_CDKN2A -? v_CYCLIN_D_c +v_ESR1 -? v_CYCLIN_D_c +v_GSK3B -? v_CYCLIN_D_c +v_MYC -? v_CYCLIN_D_c +v_P21 -? v_CYCLIN_D_c +v_TCF4 -? v_CYCLIN_D_c +v_TEAD1 -? v_CYCLIN_D_c +v_BAK1 -? v_CYCS +v_BAX -? v_CYCS +v_APC -? v_DC +v_GSK3B -? v_DC +v_FZD3 -? v_DVL1 +v_NF1 -? v_DVL1 +v_PRB -? v_E2F1 +v_EGF -? v_EGFR +v_HER2 -? v_EGFR +v_HER3 -? v_EGFR +v_MEK_i -? v_EGFR +v_IVEBP1 -? v_EIF4E +v_MEK_i -? v_ERK_i +v_AKT_i -? v_ESR1 +v_ES -? v_ESR1 +v_FOXO3 -? v_ESR1 +v_KMT2D -? v_ESR1 +v_PGR -? v_ESR1 +v_FAS -? v_FADD +v_TRADD -? v_FADD +v_AKT_i -? v_FAS +v_FASLG -? v_FAS +v_P53 -? v_FAS +v_FASLG -? v_FASLG +v_FOXO3 -? v_FASLG +v_P53 -? v_FASLG +v_AKT_i -? v_FOXO1 +v_SGK1 -? v_FOXO1 +v_AKT_i -? v_FOXO3 +v_CREB1 -? v_FZD3 +v_WNT1 -? v_FZD3 +v_STAT1 -? v_GATA3 +v_EGFR -? v_GRB2 +v_IRS1 -? v_GRB2 +v_LATS1 -? v_GRB2 +v_SRC -? v_GRB2 +v_INSR -? v_GRB7 +v_PRKACA -? v_GRB7 +v_AKT_i -? v_GSK3B +v_ERK_i -? v_GSK3B +v_EGF -? v_HER2 +v_HER3 -? v_HER2 +v_HER2 -? v_HER3 +v_NRG1 -? v_HER3 +v_CASP3 -? v_HES1 +v_NCID -? v_HES1 +v_NCID -? v_HEY1 +v_IGF1 -? v_HRAS +v_NF1 -? v_HRAS +v_PI3K_c -? v_HRAS +v_SOS1 -? v_HRAS +v_PDPK1 -? v_HSP90AA1 +v_ESR1 -? v_IGF1R +v_FOXO3 -? v_IGF1R +v_IGF1 -? v_IGF1R +v_INS -? v_IGF1R +v_SRC -? v_IGF1R +v_NOS3 -? v_IL1B +v_RELA -? v_IL1B +v_IL1B -? v_IL6 +v_IL6 -? v_IL6 +v_IL6 -? v_IL6R +v_STAT5 -? v_IL8 +v_FOXO3 -? v_INSR +v_INS -? v_INSR +v_IGF1R -? v_IRS1 +v_INSR -? v_IRS1 +v_S6K1 -? v_IRS1 +v_MTORC1_c -? v_IVEBP1 +v_ABL1 -? v_JAK2 +v_IL6R -? v_JAK2 +v_IL8 -? v_JAK2 +v_IRS1 -? v_JAK2 +v_ERK_i -? v_JUN +v_MAPK8 -? v_JUN +v_PPARG -? v_JUN +v_RELA -? v_JUN +v_AKT_i -? v_KMT2D +v_PAX7 -? v_KMT2D +v_EGFR -? v_KRT14 +v_PAK2 -? v_KRT14 +v_LCK -? v_LATS1 +v_NF2 -? v_LATS1 +v_AKT_i -? v_LCK +v_ERK_i -? v_LCK +v_RAC1 -? v_MAPK8 +v_RND1 -? v_MAPK8 +v_ERK_i -? v_MCL1 +v_GSK3B -? v_MCL1 +v_AKT_i -? v_MDM2 +v_P53 -? v_MDM2 +v_RAF1 -? v_MEK_i +v_IGF1 -? v_MTORC1_c +v_NRG1 -? v_MTORC1_c +v_RHEB -? v_MTORC1_c +v_PIP3 -? v_MTORC2_c +v_S6K1 -? v_MTORC2_c +v_CTNNB1 -? v_MYC +v_EIF4E -? v_MYC +v_ERK_i -? v_MYC +v_ESR1 -? v_MYC +v_GSK3B -? v_MYC +v_PIM -? v_MYC +v_STAT3 -? v_MYC +v_ABL1 -? v_MYOD1 +v_HES1 -? v_MYOD1 +v_HEY1 -? v_MYOG +v_MYOD1 -? v_MYOG +v_NOTCH1 -? v_NCID +v_PRKACA -? v_NEDD4L +v_S6K1 -? v_NEDD4L +v_SGK1 -? v_NEDD4L +v_P53 -? v_NF1 +v_TWIST1 -? v_NF1 +v_NEDD4L -? v_NF2 +v_NOTCH1 -? v_NFKB1 +v_AKT_i -? v_NOS3 +v_HSP90AA1 -? v_NOS3 +v_CTNNB1 -? v_NOTCH1 +v_DLL_i -? v_NOTCH1 +v_LCK -? v_NOTCH1 +v_MDM2 -? v_NOTCH1 +v_AKT_i -? v_P21 +v_ERK_i -? v_P21 +v_MYC -? v_P21 +v_MDM2 -? v_P53 +v_TCF4 -? v_PAK1 +v_RAC1 -? v_PAK2 +v_SRC -? v_PAK2 +v_HES1 -? v_PAX7 +v_HEY1 -? v_PAX7 +v_MYOG -? v_PAX7 +v_NOTCH1 -? v_PAX7 +v_IGF1R -? v_PDPK1 +v_PIP3 -? v_PDPK1 +v_ERK_i -? v_PGR +v_ESR1 -? v_PGR +v_PG -? v_PGR +v_EGFR -? v_PI3K_c +v_ESR1 -? v_PI3K_c +v_IGF1R -? v_PI3K_c +v_INSR -? v_PI3K_c +v_IRS1 -? v_PI3K_c +v_RAS_i -? v_PI3K_c +v_STAT5 -? v_PIM +v_PI3K_c -? v_PIP3 +v_PTEN -? v_PIP3 +v_CEBPB -? v_PPARG +v_GATA3 -? v_PPARG +v_CYCLIN_D_c -? v_PRB +v_PRKACA -? v_PRKAA2 +v_STK11 -? v_PRKAA2 +v_AKT_i -? v_PRKACA +v_WNT1 -? v_PRKACA +v_S6K1 -? v_PTEN +v_SRC -? v_PTEN +v_AKT_i -? v_RAC1 +v_DVL1 -? v_RAC1 +v_PI3K_c -? v_RAC1 +v_HRAS -? v_RAF1 +v_RAS_i -? v_RAF1 +v_IGF1 -? v_RAS_i +v_PI3K_c -? v_RAS_i +v_SOS1 -? v_RAS_i +v_NFKB1 -? v_RELA +v_PIM -? v_RELA +v_TSC2 -? v_RHEB +v_DVL1 -? v_RND1 +v_GRB7 -? v_RND1 +v_MTORC1_c -? v_S6K1 +v_MTORC1_c -? v_SGK1 +v_MTORC2_c -? v_SGK1 +v_PDPK1 -? v_SGK1 +v_GRB2 -? v_SOS1 +v_ABL1 -? v_SRC +v_PRKACA -? v_SRC +v_JAK2 -? v_STAT1 +v_SRC -? v_STAT1 +v_IL1B -? v_STAT3 +v_JAK2 -? v_STAT3 +v_MAPK8 -? v_STAT3 +v_SRC -? v_STAT3 +v_EGFR -? v_STAT5 +v_JAK2 -? v_STAT5 +v_SRC -? v_STAT5 +v_ERK_i -? v_STK11 +v_CTNNB1 -? v_TCF4 +v_JUN -? v_TCF4 +v_YAP1 -? v_TEAD1 +v_KRT14 -? v_TRADD +v_AKT_i -? v_TSC2 +v_ERK_i -? v_TSC2 +v_GSK3B -? v_TSC2 +v_PRKAA2 -? v_TSC2 +v_AKT_i -? v_TWIST1 +v_ERK_i -? v_TWIST1 +v_MAPK8 -? v_TWIST1 +v_PGR -? v_WNT1 +v_WNT1 -? v_WNT1 +v_ABL1 -? v_YAP1 +v_LATS1 -? v_YAP1 +$v_ABL1: (v_SRC | v_GRB2) +$v_ABL2: v_ABL1 +$v_AKT_i: ((((v_MTORC2_c & v_PDPK1) & v_PIP3) & (v_IRS1 | v_IGF1R)) | (v_NRG1 | v_IGF1)) +$v_APC: v_AXIN1 +$v_AXIN1: (!v_DVL1 & v_GSK3B) +$v_BAD: !(v_PAK1 | (v_AKT_i | (v_ERK_i | v_PIM))) +$v_BAK1: (((v_BIM | v_P53) | v_BID) & !v_MCL1) +$v_BAX: (((v_BIM | v_P53) | v_BID) & !v_MCL1) +$v_BCL2: (!(v_BAD | v_BIM) & (v_CREB1 | v_ERK_i)) +$v_BCLXL: (!(v_BAD | v_BIM) & v_CREB1) +$v_BID: v_CASP8 +$v_BIM: (!(v_BCL2 | v_BCLXL) & (v_FOXO3 | v_FOXO1)) +$v_CASP3: v_CASP9 +$v_CASP8: ((v_FADD | v_NF1) & !(v_ERK_i & v_SRC)) +$v_CASP9: (((v_CYCS | v_CASP8) | v_CASP3) & !((v_ERK_i | v_PRKACA) | (v_BCLXL | v_AKT_i))) +$v_CDKN2A: (!(v_MYC | v_SRC) & v_CASP3) +$v_CEBPB: (v_ABL2 | v_CREB1) +$v_CREB1: (v_AKT_i & !v_PTEN) +$v_CTNNB1: (!v_DC & (v_WNT1 | (v_SRC | v_YAP1))) +$v_CYCLIN_D_c: ((v_TCF4 | (v_TEAD1 | (v_ESR1 | v_MYC))) & !(v_GSK3B | (v_CDKN2A | v_P21))) +$v_CYCS: (v_BAK1 | v_BAX) +$v_DC: (v_APC & v_GSK3B) +$v_DVL1: (v_FZD3 | v_NF1) +$v_E2F1: !v_PRB +$v_EGFR: ((v_EGF | (v_HER2 & v_HER3)) & !v_MEK_i) +$v_EIF4E: !v_IVEBP1 +$v_ERK_i: v_MEK_i +$v_ESR1: (v_AKT_i | (v_FOXO3 | (v_ES | (v_PGR | v_KMT2D)))) +$v_FADD: (v_TRADD | v_FAS) +$v_FAS: ((v_FASLG | v_P53) & !v_AKT_i) +$v_FASLG: (v_FASLG | (v_P53 | v_FOXO3)) +$v_FOXO1: !(v_SGK1 | v_AKT_i) +$v_FOXO3: !v_AKT_i +$v_FZD3: (v_WNT1 | v_CREB1) +$v_GATA3: !v_STAT1 +$v_GRB2: (v_IRS1 | (v_LATS1 | (v_EGFR | v_SRC))) +$v_GRB7: (v_INSR & !v_PRKACA) +$v_GSK3B: !(v_AKT_i | v_ERK_i) +$v_HER2: (v_HER3 | v_EGF) +$v_HER3: (v_NRG1 | v_HER2) +$v_HES1: (v_NCID & !v_CASP3) +$v_HEY1: v_NCID +$v_HRAS: (((v_SOS1 | v_PI3K_c) & !v_NF1) | (v_PI3K_c | v_IGF1)) +$v_HSP90AA1: !v_PDPK1 +$v_IGF1R: ((v_IGF1 | (v_SRC | v_INS)) | (v_FOXO3 | v_ESR1)) +$v_IL1B: (v_NOS3 | v_RELA) +$v_IL6: (v_IL1B | v_IL6) +$v_IL6R: v_IL6 +$v_IL8: v_STAT5 +$v_INSR: (v_INS | v_FOXO3) +$v_IRS1: (!v_S6K1 & (v_INSR | v_IGF1R)) +$v_IVEBP1: !v_MTORC1_c +$v_JAK2: ((v_IL6R | (v_ABL1 | v_IL8)) | v_IRS1) +$v_JUN: ((v_RELA | v_MAPK8) & (v_ERK_i | v_PPARG)) +$v_KMT2D: (v_PAX7 & !v_AKT_i) +$v_KRT14: (v_PAK2 | v_EGFR) +$v_LATS1: (v_NF2 | v_LCK) +$v_LCK: (v_ERK_i & !v_AKT_i) +$v_MAPK8: (v_RAC1 | v_RND1) +$v_MCL1: (!v_GSK3B & v_ERK_i) +$v_MDM2: (v_P53 | v_AKT_i) +$v_MEK_i: v_RAF1 +$v_MTORC1_c: (v_RHEB | (v_NRG1 | v_IGF1)) +$v_MTORC2_c: (v_PIP3 & !v_S6K1) +$v_MYC: ((v_CTNNB1 | (v_PIM | (v_ERK_i | (v_STAT3 | (v_ESR1 | v_EIF4E))))) & !v_GSK3B) +$v_MYOD1: !(v_HES1 | v_ABL1) +$v_MYOG: (!v_HEY1 & v_MYOD1) +$v_NCID: v_NOTCH1 +$v_NEDD4L: !(v_S6K1 | (v_SGK1 | v_PRKACA)) +$v_NF1: (!v_TWIST1 & v_P53) +$v_NF2: v_NEDD4L +$v_NFKB1: v_NOTCH1 +$v_NOS3: (v_HSP90AA1 | v_AKT_i) +$v_NOTCH1: ((v_DLL_i | (v_CTNNB1 | v_LCK)) | v_MDM2) +$v_P21: !(v_ERK_i | (v_AKT_i | v_MYC)) +$v_P53: !v_MDM2 +$v_PAK1: v_TCF4 +$v_PAK2: (v_RAC1 | v_SRC) +$v_PAX7: (!(v_MYOG | (v_HEY1 | v_HES1)) & v_NOTCH1) +$v_PDPK1: (v_PIP3 | v_IGF1R) +$v_PGR: (v_PG & !(v_ERK_i | v_ESR1)) +$v_PI3K_c: ((v_EGFR | (v_INSR | (v_RAS_i | v_ESR1))) | (v_IRS1 | v_IGF1R)) +$v_PIM: v_STAT5 +$v_PIP3: (v_PI3K_c & !v_PTEN) +$v_PPARG: (!v_GATA3 & v_CEBPB) +$v_PRB: !v_CYCLIN_D_c +$v_PRKAA2: (v_STK11 | !v_PRKACA) +$v_PRKACA: (v_AKT_i | v_WNT1) +$v_PTEN: (v_S6K1 & !v_SRC) +$v_RAC1: ((v_PI3K_c | v_DVL1) & !v_AKT_i) +$v_RAF1: (v_HRAS | v_RAS_i) +$v_RAS_i: ((v_SOS1 | v_PI3K_c) | (v_PI3K_c | v_IGF1)) +$v_RELA: (v_NFKB1 | v_PIM) +$v_RHEB: !v_TSC2 +$v_RND1: (v_GRB7 | v_DVL1) +$v_S6K1: v_MTORC1_c +$v_SGK1: ((v_MTORC2_c | v_MTORC1_c) | v_PDPK1) +$v_SOS1: v_GRB2 +$v_SRC: (v_PRKACA | v_ABL1) +$v_STAT1: (v_JAK2 | v_SRC) +$v_STAT3: (v_IL1B | (v_SRC | (v_MAPK8 | v_JAK2))) +$v_STAT5: (v_JAK2 | (v_SRC | v_EGFR)) +$v_STK11: !v_ERK_i +$v_TCF4: (v_CTNNB1 | v_JUN) +$v_TEAD1: v_YAP1 +$v_TRADD: !v_KRT14 +$v_TSC2: (!(v_AKT_i | v_ERK_i) & (v_PRKAA2 | v_GSK3B)) +$v_TWIST1: (v_ERK_i | (v_AKT_i | v_MAPK8)) +$v_WNT1: (v_PGR | v_WNT1) +$v_YAP1: (!v_LATS1 & v_ABL1) diff --git a/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.bnet b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.bnet new file mode 100644 index 0000000..5989390 --- /dev/null +++ b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.bnet @@ -0,0 +1,111 @@ +targets,factors +v_ABL1, (v_SRC | v_GRB2) +v_ABL2, v_ABL1 +v_AKT_i, ((((v_MTORC2_c & v_PDPK1) & v_PIP3) & (v_IRS1 | v_IGF1R)) | (v_NRG1 | v_IGF1)) +v_APC, v_AXIN1 +v_AXIN1, (!v_DVL1 & v_GSK3B) +v_BAD, !(v_PAK1 | (v_AKT_i | (v_ERK_i | v_PIM))) +v_BAK1, (((v_BIM | v_P53) | v_BID) & !v_MCL1) +v_BAX, (((v_BIM | v_P53) | v_BID) & !v_MCL1) +v_BCL2, (!(v_BAD | v_BIM) & (v_CREB1 | v_ERK_i)) +v_BCLXL, (!(v_BAD | v_BIM) & v_CREB1) +v_BID, v_CASP8 +v_BIM, (!(v_BCL2 | v_BCLXL) & (v_FOXO3 | v_FOXO1)) +v_CASP3, v_CASP9 +v_CASP8, ((v_FADD | v_NF1) & !(v_ERK_i & v_SRC)) +v_CASP9, (((v_CYCS | v_CASP8) | v_CASP3) & !((v_ERK_i | v_PRKACA) | (v_BCLXL | v_AKT_i))) +v_CDKN2A, (!(v_MYC | v_SRC) & v_CASP3) +v_CEBPB, (v_ABL2 | v_CREB1) +v_CREB1, (v_AKT_i & !v_PTEN) +v_CTNNB1, (!v_DC & (v_WNT1 | (v_SRC | v_YAP1))) +v_CYCLIN_D_c, ((v_TCF4 | (v_TEAD1 | (v_ESR1 | v_MYC))) & !(v_GSK3B | (v_CDKN2A | v_P21))) +v_CYCS, (v_BAK1 | v_BAX) +v_DC, (v_APC & v_GSK3B) +v_DVL1, (v_FZD3 | v_NF1) +v_E2F1, !v_PRB +v_EGFR, ((v_EGF | (v_HER2 & v_HER3)) & !v_MEK_i) +v_EIF4E, !v_IVEBP1 +v_ERK_i, v_MEK_i +v_ESR1, (v_AKT_i | (v_FOXO3 | (v_ES | (v_PGR | v_KMT2D)))) +v_FADD, (v_TRADD | v_FAS) +v_FAS, ((v_FASLG | v_P53) & !v_AKT_i) +v_FASLG, (v_FASLG | (v_P53 | v_FOXO3)) +v_FOXO1, !(v_SGK1 | v_AKT_i) +v_FOXO3, !v_AKT_i +v_FZD3, (v_WNT1 | v_CREB1) +v_GATA3, !v_STAT1 +v_GRB2, (v_IRS1 | (v_LATS1 | (v_EGFR | v_SRC))) +v_GRB7, (v_INSR & !v_PRKACA) +v_GSK3B, !(v_AKT_i | v_ERK_i) +v_HER2, (v_HER3 | v_EGF) +v_HER3, (v_NRG1 | v_HER2) +v_HES1, (v_NCID & !v_CASP3) +v_HEY1, v_NCID +v_HRAS, (((v_SOS1 | v_PI3K_c) & !v_NF1) | (v_PI3K_c | v_IGF1)) +v_HSP90AA1, !v_PDPK1 +v_IGF1R, ((v_IGF1 | (v_SRC | v_INS)) | (v_FOXO3 | v_ESR1)) +v_IL1B, (v_NOS3 | v_RELA) +v_IL6, (v_IL1B | v_IL6) +v_IL6R, v_IL6 +v_IL8, v_STAT5 +v_INSR, (v_INS | v_FOXO3) +v_IRS1, (!v_S6K1 & (v_INSR | v_IGF1R)) +v_IVEBP1, !v_MTORC1_c +v_JAK2, ((v_IL6R | (v_ABL1 | v_IL8)) | v_IRS1) +v_JUN, ((v_RELA | v_MAPK8) & (v_ERK_i | v_PPARG)) +v_KMT2D, (v_PAX7 & !v_AKT_i) +v_KRT14, (v_PAK2 | v_EGFR) +v_LATS1, (v_NF2 | v_LCK) +v_LCK, (v_ERK_i & !v_AKT_i) +v_MAPK8, (v_RAC1 | v_RND1) +v_MCL1, (!v_GSK3B & v_ERK_i) +v_MDM2, (v_P53 | v_AKT_i) +v_MEK_i, v_RAF1 +v_MTORC1_c, (v_RHEB | (v_NRG1 | v_IGF1)) +v_MTORC2_c, (v_PIP3 & !v_S6K1) +v_MYC, ((v_CTNNB1 | (v_PIM | (v_ERK_i | (v_STAT3 | (v_ESR1 | v_EIF4E))))) & !v_GSK3B) +v_MYOD1, !(v_HES1 | v_ABL1) +v_MYOG, (!v_HEY1 & v_MYOD1) +v_NCID, v_NOTCH1 +v_NEDD4L, !(v_S6K1 | (v_SGK1 | v_PRKACA)) +v_NF1, (!v_TWIST1 & v_P53) +v_NF2, v_NEDD4L +v_NFKB1, v_NOTCH1 +v_NOS3, (v_HSP90AA1 | v_AKT_i) +v_NOTCH1, ((v_DLL_i | (v_CTNNB1 | v_LCK)) | v_MDM2) +v_P21, !(v_ERK_i | (v_AKT_i | v_MYC)) +v_P53, !v_MDM2 +v_PAK1, v_TCF4 +v_PAK2, (v_RAC1 | v_SRC) +v_PAX7, (!(v_MYOG | (v_HEY1 | v_HES1)) & v_NOTCH1) +v_PDPK1, (v_PIP3 | v_IGF1R) +v_PGR, (v_PG & !(v_ERK_i | v_ESR1)) +v_PI3K_c, ((v_EGFR | (v_INSR | (v_RAS_i | v_ESR1))) | (v_IRS1 | v_IGF1R)) +v_PIM, v_STAT5 +v_PIP3, (v_PI3K_c & !v_PTEN) +v_PPARG, (!v_GATA3 & v_CEBPB) +v_PRB, !v_CYCLIN_D_c +v_PRKAA2, (v_STK11 | !v_PRKACA) +v_PRKACA, (v_AKT_i | v_WNT1) +v_PTEN, (v_S6K1 & !v_SRC) +v_RAC1, ((v_PI3K_c | v_DVL1) & !v_AKT_i) +v_RAF1, (v_HRAS | v_RAS_i) +v_RAS_i, ((v_SOS1 | v_PI3K_c) | (v_PI3K_c | v_IGF1)) +v_RELA, (v_NFKB1 | v_PIM) +v_RHEB, !v_TSC2 +v_RND1, (v_GRB7 | v_DVL1) +v_S6K1, v_MTORC1_c +v_SGK1, ((v_MTORC2_c | v_MTORC1_c) | v_PDPK1) +v_SOS1, v_GRB2 +v_SRC, (v_PRKACA | v_ABL1) +v_STAT1, (v_JAK2 | v_SRC) +v_STAT3, (v_IL1B | (v_SRC | (v_MAPK8 | v_JAK2))) +v_STAT5, (v_JAK2 | (v_SRC | v_EGFR)) +v_STK11, !v_ERK_i +v_TCF4, (v_CTNNB1 | v_JUN) +v_TEAD1, v_YAP1 +v_TRADD, !v_KRT14 +v_TSC2, (!(v_AKT_i | v_ERK_i) & (v_PRKAA2 | v_GSK3B)) +v_TWIST1, (v_ERK_i | (v_AKT_i | v_MAPK8)) +v_WNT1, (v_PGR | v_WNT1) +v_YAP1, (!v_LATS1 & v_ABL1) diff --git a/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.sbml b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.sbml new file mode 100644 index 0000000..9e1840d --- /dev/null +++ b/models/[id-231]__[var-110]__[in-7]__[BREAST-CANCER-SIGNALLING-PATHWAYS]/model.sbml @@ -0,0 +1 @@ +v_SRC1v_GRB21v_ABL11v_MTORC2_c1v_PDPK11v_PIP31v_IRS11v_IGF1R1v_NRG11v_IGF11v_AXIN11v_DVL11v_GSK3B1v_PAK11v_AKT_i1v_ERK_i1v_PIM1v_BIM1v_P531v_BID1v_MCL11v_BIM1v_P531v_BID1v_MCL11v_BAD1v_BIM1v_CREB11v_ERK_i1v_BAD1v_BIM1v_CREB11v_CASP81v_BCL21v_BCLXL1v_FOXO31v_FOXO11v_CASP91v_FADD1v_NF11v_ERK_i1v_SRC1v_CYCS1v_CASP81v_CASP31v_ERK_i1v_PRKACA1v_BCLXL1v_AKT_i1v_MYC1v_SRC1v_CASP31v_ABL21v_CREB11v_AKT_i1v_PTEN1v_DC1v_WNT11v_SRC1v_YAP11v_TCF41v_TEAD11v_ESR11v_MYC1v_GSK3B1v_CDKN2A1v_P211v_BAK11v_BAX1v_APC1v_GSK3B1v_FZD31v_NF11v_PRB1v_EGF1v_HER21v_HER31v_MEK_i1v_IVEBP11v_MEK_i1v_AKT_i1v_FOXO31v_ES1v_PGR1v_KMT2D1v_TRADD1v_FAS1v_FASLG1v_P531v_AKT_i1v_FASLG1v_P531v_FOXO31v_SGK11v_AKT_i1v_AKT_i1v_WNT11v_CREB11v_STAT11v_IRS11v_LATS11v_EGFR1v_SRC1v_INSR1v_PRKACA1v_AKT_i1v_ERK_i1v_HER31v_EGF1v_NRG11v_HER21v_NCID1v_CASP31v_NCID1v_SOS11v_PI3K_c1v_NF11v_PI3K_c1v_IGF11v_PDPK11v_IGF11v_SRC1v_INS1v_FOXO31v_ESR11v_NOS31v_RELA1v_IL1B1v_IL61v_IL61v_STAT51v_INS1v_FOXO31v_S6K11v_INSR1v_IGF1R1v_MTORC1_c1v_IL6R1v_ABL11v_IL81v_IRS11v_RELA1v_MAPK81v_ERK_i1v_PPARG1v_PAX71v_AKT_i1v_PAK21v_EGFR1v_NF21v_LCK1v_ERK_i1v_AKT_i1v_RAC11v_RND11v_GSK3B1v_ERK_i1v_P531v_AKT_i1v_RAF11v_RHEB1v_NRG11v_IGF11v_PIP31v_S6K11v_CTNNB11v_PIM1v_ERK_i1v_STAT31v_ESR11v_EIF4E1v_GSK3B1v_HES11v_ABL11v_HEY11v_MYOD11v_NOTCH11v_S6K11v_SGK11v_PRKACA1v_TWIST11v_P531v_NEDD4L1v_NOTCH11v_HSP90AA11v_AKT_i1v_DLL_i1v_CTNNB11v_LCK1v_MDM21v_ERK_i1v_AKT_i1v_MYC1v_MDM21v_TCF41v_RAC11v_SRC1v_MYOG1v_HEY11v_HES11v_NOTCH11v_PIP31v_IGF1R1v_PG1v_ERK_i1v_ESR11v_EGFR1v_INSR1v_RAS_i1v_ESR11v_IRS11v_IGF1R1v_STAT51v_PI3K_c1v_PTEN1v_GATA31v_CEBPB1v_CYCLIN_D_c1v_STK111v_PRKACA1v_AKT_i1v_WNT11v_S6K11v_SRC1v_PI3K_c1v_DVL11v_AKT_i1v_HRAS1v_RAS_i1v_SOS11v_PI3K_c1v_PI3K_c1v_IGF11v_NFKB11v_PIM1v_TSC21v_GRB71v_DVL11v_MTORC1_c1v_MTORC2_c1v_MTORC1_c1v_PDPK11v_GRB21v_PRKACA1v_ABL11v_JAK21v_SRC1v_IL1B1v_SRC1v_MAPK81v_JAK21v_JAK21v_SRC1v_EGFR1v_ERK_i1v_CTNNB11v_JUN1v_YAP11v_KRT141v_AKT_i1v_ERK_i1v_PRKAA21v_GSK3B1v_ERK_i1v_AKT_i1v_MAPK81v_PGR1v_WNT11v_LATS11v_ABL11 \ No newline at end of file diff --git a/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/citation.bib b/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/citation.bib new file mode 100644 index 0000000..809c357 --- /dev/null +++ b/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/citation.bib @@ -0,0 +1,8 @@ +@article{bbm-231, + author = {Taoma, Kittisak and Ruengjitchatchawalya, Marasri and Liangruksa, Monrudee and Laomettachit, Teeraphan}, + year = {2024}, + doi = {https://doi.org/10.1371/journal.pone.0298788}, + title = {Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy}, + publisher = {PLOS ONE} +} + diff --git a/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/metadata.json b/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/metadata.json new file mode 100644 index 0000000..64f4414 --- /dev/null +++ b/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/metadata.json @@ -0,0 +1,7 @@ +{ + "id": 231, + "name": "BREAST-CANCER-SIGNALLING-PATHWAYS", + "url-publication": "https://doi.org/10.1371/journal.pone.0298788", + "url-model": "https://github.com/Ktaoma/BoolSyn", + "keywords": ["source (?)","curated (?)","repaired (?)", "multi-valued (?)"] +} diff --git a/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/notes.md b/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/notes.md new file mode 100644 index 0000000..d911734 --- /dev/null +++ b/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/notes.md @@ -0,0 +1,11 @@ +### Modifications + +Rows deleted from the source file: + +DLL_i, DLL_i +IGF1, IGF1 +NRG1, NRG1 +PG, PG +ES, ES +EGF, EGF +INS, INS diff --git a/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/source.bnet b/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/source.bnet new file mode 100644 index 0000000..3d1f0cc --- /dev/null +++ b/sources/231_BREAST-CANCER-SIGNALLING-PATHWAYS/source.bnet @@ -0,0 +1,111 @@ +IL6, IL1B|IL6 +IL6R, IL6 +JAK2, (IL6R|ABL1|IL8)|IRS1 +STAT5, JAK2|SRC|EGFR +IL8, STAT5 +PIM, STAT5 +STAT3, IL1B|SRC|MAPK8 |JAK2 +STAT1, JAK2|SRC +GATA3, !STAT1 +PPARG, !GATA3&CEBPB +WNT1, PGR|WNT1 +FZD3, WNT1|CREB1 +DVL1, FZD3|NF1 +AXIN1, !DVL1&GSK3B +APC, AXIN1 +DC, APC&GSK3B +CTNNB1, !DC&(WNT1|SRC|YAP1) +TCF4, CTNNB1|JUN +PAK1, TCF4 +NOTCH1, (DLL_i|CTNNB1|LCK)|MDM2 +NFKB1, NOTCH1 +RELA, NFKB1|PIM +JUN, (RELA|MAPK8)&(ERK_i|PPARG) +NCID, NOTCH1 +HES1, NCID&!CASP3 +HEY1, NCID +MYOD1, !(HES1|ABL1) +MYOG, !HEY1&MYOD1 +PAX7, !(MYOG|HEY1|HES1)&NOTCH1 +KMT2D, PAX7&!AKT_i +IGF1R, (IGF1|SRC|INS)|(FOXO3|ESR1) +HER3, NRG1|HER2 +HER2, HER3|EGF +PGR, PG &!(ERK_i|ESR1) +ESR1, AKT_i|FOXO3|(ES|PGR|KMT2D) +EGFR, (EGF|(HER2&HER3))&!MEK_i +GRB2, IRS1|(LATS1|(EGFR|SRC)) +SOS1, GRB2 +HRAS, ((SOS1|PI3K_c)&!NF1)|(PI3K_c|IGF1) +RAS_i, (SOS1|PI3K_c)|(PI3K_c|IGF1) +RAF1, (HRAS|RAS_i) +MEK_i, RAF1 +ERK_i, MEK_i +LCK, ERK_i&!AKT_i +TWIST1, ERK_i|AKT_i|MAPK8 +NF1, !TWIST1&P53 +PI3K_c, (EGFR|INSR|RAS_i|ESR1)|(IRS1|IGF1R ) +PTEN, S6K1&!SRC +PIP3, PI3K_c&!PTEN +PDPK1, PIP3|IGF1R +MTORC2_c, PIP3&!S6K1 +AKT_i, (((MTORC2_c&PDPK1)&PIP3)&(IRS1|IGF1R))|(NRG1|IGF1) +FOXO3, !AKT_i +FOXO1, !(SGK1|AKT_i) +CREB1, AKT_i&!PTEN +GSK3B, !(AKT_i|ERK_i) +TSC2, !(AKT_i|ERK_i)&(PRKAA2|GSK3B) +RHEB, !TSC2 +MTORC1_c, RHEB|(NRG1|IGF1) +S6K1, MTORC1_c +IRS1, !S6K1&(INSR|IGF1R) +SGK1, (MTORC2_c|MTORC1_c)|PDPK1 +NEDD4L, !(S6K1|SGK1|PRKACA) +NF2, NEDD4L +LATS1, NF2|LCK +YAP1, !LATS1&ABL1 +TEAD1, YAP1 +IVEBP1, !MTORC1_c +EIF4E, !IVEBP1 +MYC, (CTNNB1|PIM|ERK_i|STAT3|ESR1|EIF4E)&!GSK3B +P21, !(ERK_i|AKT_i|MYC) +CYCLIN_D_c, ((TCF4|TEAD1|ESR1|MYC)&!(GSK3B|(CDKN2A|P21))) +PRB, !CYCLIN_D_c +E2F1, !PRB +P53, !MDM2 +MDM2, P53|AKT_i +MCL1, !GSK3B&ERK_i +BAD, !( PAK1|AKT_i|ERK_i|PIM) +BCL2, !(BAD|BIM)&(CREB1|ERK_i) +BCLXL, !(BAD|BIM)&CREB1 +BIM, !(BCL2|BCLXL)&(FOXO3|FOXO1) +BID, CASP8 +BAK1, ((BIM|P53)|BID)&!MCL1 +BAX, ((BIM|P53)|BID)&!MCL1 +CYCS, BAK1|BAX +CASP9, ((CYCS|CASP8)|CASP3)&!((ERK_i|PRKACA)|(BCLXL|AKT_i)) +CASP3, CASP9 +HSP90AA1, !PDPK1 +NOS3, HSP90AA1|AKT_i +IL1B, NOS3|RELA +STK11, !ERK_i +PRKAA2, STK11|!PRKACA +PAK2, RAC1|SRC +KRT14, PAK2|EGFR +TRADD, !KRT14 +FASLG, FASLG|P53|FOXO3 +FAS, (FASLG|P53)&!AKT_i +FADD, TRADD|FAS +CASP8, (FADD|NF1)&!(ERK_i&SRC) +PRKACA, AKT_i|WNT1 +SRC, PRKACA|ABL1 +ABL1, (SRC|GRB2) +ABL2, ABL1 +CEBPB, ABL2|CREB1 +CDKN2A, !(MYC|SRC)&CASP3 +INSR, INS|FOXO3 +GRB7, INSR&!PRKACA +RND1, GRB7|DVL1 +RAC1, (PI3K_c|DVL1)&!AKT_i +MAPK8, RAC1|RND1 + From d357360603441e59b2e78771ed63ecad40e1ac4f Mon Sep 17 00:00:00 2001 From: Samuel Pastva Date: Fri, 20 Sep 2024 14:13:45 +0200 Subject: [PATCH 3/6] New output mechanism in workflow. --- .github/workflows/integrity.yml | 11 +++++++---- 1 file changed, 7 insertions(+), 4 deletions(-) diff --git a/.github/workflows/integrity.yml b/.github/workflows/integrity.yml index a1f1e08..595426e 100644 --- a/.github/workflows/integrity.yml +++ b/.github/workflows/integrity.yml @@ -18,9 +18,12 @@ jobs: run: rm -rf models/* - name: Run a fresh model sync. run: python3 sync.py - - name: Check if there is any change - id: get_changes - run: echo "::set-output name=changed::$(git status --porcelain | wc -l)" + - name: Check for changes + id: check_changes + run: | + if [[ -n $(git status --porcelain) ]]; then + echo "changes=true" >> "$GITHUB_OUTPUT"; + fi - name: If there are changes, fail. - if: steps.get_changes.outputs.changed != 0 + if: steps.check_changes.outputs.changed != 0 run: exit 1 \ No newline at end of file From e12e1fa9dcabac4441f418c0b06b1f1e0a19697f Mon Sep 17 00:00:00 2001 From: Samuel Pastva Date: Fri, 20 Sep 2024 14:16:46 +0200 Subject: [PATCH 4/6] Update checkout package. --- .github/workflows/integrity.yml | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/.github/workflows/integrity.yml b/.github/workflows/integrity.yml index 595426e..8de1f5d 100644 --- a/.github/workflows/integrity.yml +++ b/.github/workflows/integrity.yml @@ -6,7 +6,7 @@ jobs: name: check runs-on: ubuntu-latest steps: - - uses: actions/checkout@v2 + - uses: actions/checkout@v4 - name: Install Python. uses: actions/setup-python@v4 with: From 07d5d8f9e59c0b90239855680b43e74911da458b Mon Sep 17 00:00:00 2001 From: Samuel Pastva Date: Fri, 20 Sep 2024 14:18:52 +0200 Subject: [PATCH 5/6] Update python package. --- .github/workflows/integrity.yml | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/.github/workflows/integrity.yml b/.github/workflows/integrity.yml index 8de1f5d..f6be364 100644 --- a/.github/workflows/integrity.yml +++ b/.github/workflows/integrity.yml @@ -8,7 +8,7 @@ jobs: steps: - uses: actions/checkout@v4 - name: Install Python. - uses: actions/setup-python@v4 + uses: actions/setup-python@v5 with: python-version: '3.10' cache: 'pip' From ba3b0cb87be9860b4d9c46852d13b820ad58e9f1 Mon Sep 17 00:00:00 2001 From: Natalia Florekova Date: Sat, 21 Sep 2024 19:29:58 +0200 Subject: [PATCH 6/6] Added model 232 - breast cancer signalling pathways MCF7 complete --- .../README.md | 37 ++ .../metadata.json | 17 + .../model.aeon | 384 ++++++++++++++++++ .../model.bnet | 110 +++++ .../model.sbml | 1 + report/.~lock.online_only_table_1.xlsx# | 1 - .../citation.bib | 8 + .../metadata.json | 7 + .../notes.md | 11 + .../source.bnet | 110 +++++ 10 files changed, 685 insertions(+), 1 deletion(-) create mode 100644 models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/README.md create mode 100644 models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/metadata.json create mode 100644 models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.aeon create mode 100644 models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.bnet create mode 100644 models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.sbml delete mode 100644 report/.~lock.online_only_table_1.xlsx# create mode 100644 sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/citation.bib create mode 100644 sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/metadata.json create mode 100644 sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/notes.md create mode 100644 sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/source.bnet diff --git a/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/README.md b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/README.md new file mode 100644 index 0000000..f3200aa --- /dev/null +++ b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/README.md @@ -0,0 +1,37 @@ +# \[232\] BREAST-CANCER-PATHWAYS-MCF7-COMPLETE + + - Variables: 109 + - Inputs: 8 + - Regulations: 275 + - Publication: https://doi.org/10.1371/journal.pone.0298788 + - Source: https://github.com/Ktaoma/BoolSyn + - Keywords: source (?), curated (?), repaired (?), multi-valued (?) + + +### Modifications + +Removed regulations: +WNT1, WNT1 +PG, PG +NRG1, NRG1 +DLL_i, DLL_i +EGF, EGF +ES, ES +IGF1, IGF1 +INS, INS + + +### Model citation + +``` +@article{bbm-232, + author = {Taoma, Kittisak and Ruengjitchatchawalya, Marasri and Liangruksa, Monrudee and Laomettachit, Teeraphan}, + year = {2024}, + doi = {https://doi.org/10.1371/journal.pone.0298788}, + title = {Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy}, + publisher = {PLOS ONE} +} + + +``` + diff --git a/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/metadata.json b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/metadata.json new file mode 100644 index 0000000..dfd8fb5 --- /dev/null +++ b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/metadata.json @@ -0,0 +1,17 @@ +{ + "id": 232, + "name": "BREAST-CANCER-PATHWAYS-MCF7-COMPLETE", + "url-publication": "https://doi.org/10.1371/journal.pone.0298788", + "url-model": "https://github.com/Ktaoma/BoolSyn", + "keywords": [ + "source (?)", + "curated (?)", + "repaired (?)", + "multi-valued (?)" + ], + "variables": 109, + "inputs": 8, + "regulations": 275, + "notes": "### Modifications\n\nRemoved regulations:\nWNT1, WNT1\nPG, PG\nNRG1, NRG1\nDLL_i, DLL_i\nEGF, EGF\nES, ES\nIGF1, IGF1\nINS, INS\n", + "bib": "@article{bbm-232,\n\tauthor = {Taoma, Kittisak and Ruengjitchatchawalya, Marasri and Liangruksa, Monrudee and Laomettachit, Teeraphan},\n\tyear = {2024},\n\tdoi = {https://doi.org/10.1371/journal.pone.0298788},\n\ttitle = {Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy},\n\tpublisher = {PLOS ONE}\n}\n\n" +} \ No newline at end of file diff --git a/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.aeon b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.aeon new file mode 100644 index 0000000..ebabe30 --- /dev/null +++ b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.aeon @@ -0,0 +1,384 @@ +v_GRB2 -? v_ABL1 +v_PRB -? v_ABL1 +v_SRC -? v_ABL1 +v_ABL1 -? v_ABL2 +v_IGF1 -? v_AKT_i +v_IGF1R -? v_AKT_i +v_IRS1 -? v_AKT_i +v_MTORC2_c -? v_AKT_i +v_NRG1 -? v_AKT_i +v_PDPK1 -? v_AKT_i +v_PIP3 -? v_AKT_i +v_AXIN1 -? v_APC +v_DVL1 -? v_AXIN1 +v_GSK3B -? v_AXIN1 +v_AKT_i -? v_BAD +v_ERK_i -? v_BAD +v_PAK1 -? v_BAD +v_PIM -? v_BAD +v_BID -? v_BAK1 +v_BIM -? v_BAK1 +v_MCL1 -? v_BAK1 +v_P53 -? v_BAK1 +v_BID -? v_BAX +v_BIM -? v_BAX +v_MCL1 -? v_BAX +v_P53 -? v_BAX +v_BAD -? v_BCL2 +v_BIM -? v_BCL2 +v_CREB1 -? v_BCL2 +v_ERK_i -? v_BCL2 +v_BAD -? v_BCLXL +v_BIM -? v_BCLXL +v_CREB1 -? v_BCLXL +v_CASP8 -? v_BID +v_BCL2 -? v_BIM +v_BCLXL -? v_BIM +v_FOXO1 -? v_BIM +v_FOXO3 -? v_BIM +v_CASP9 -? v_CASP3 +v_ERK_i -? v_CASP8 +v_FADD -? v_CASP8 +v_NF1 -? v_CASP8 +v_SRC -? v_CASP8 +v_AKT_i -? v_CASP9 +v_BCLXL -? v_CASP9 +v_CASP3 -? v_CASP9 +v_CASP8 -? v_CASP9 +v_CYCS -? v_CASP9 +v_ERK_i -? v_CASP9 +v_PRKACA -? v_CASP9 +v_CASP3 -? v_CDKN2A +v_MYC -? v_CDKN2A +v_SRC -? v_CDKN2A +v_ABL2 -? v_CEBPB +v_CREB1 -? v_CEBPB +v_AKT_i -? v_CREB1 +v_PTEN -? v_CREB1 +v_DC -? v_CTNNB1 +v_SRC -? v_CTNNB1 +v_WNT1 -? v_CTNNB1 +v_YAP1 -? v_CTNNB1 +v_CDKN2A -? v_CYCLIN_D_c +v_EIF4E -? v_CYCLIN_D_c +v_ESR1 -? v_CYCLIN_D_c +v_FOXO3 -? v_CYCLIN_D_c +v_GSK3B -? v_CYCLIN_D_c +v_IGF1 -? v_CYCLIN_D_c +v_KMT2D -? v_CYCLIN_D_c +v_MYC -? v_CYCLIN_D_c +v_NRG1 -? v_CYCLIN_D_c +v_P21 -? v_CYCLIN_D_c +v_TCF4 -? v_CYCLIN_D_c +v_TEAD1 -? v_CYCLIN_D_c +v_BAK1 -? v_CYCS +v_BAX -? v_CYCS +v_APC -? v_DC +v_GSK3B -? v_DC +v_FZD3 -? v_DVL1 +v_NF1 -? v_DVL1 +v_PRB -? v_E2F1 +v_EGF -? v_EGFR +v_HER2 -? v_EGFR +v_HER3 -? v_EGFR +v_MEK_i -? v_EGFR +v_IVEBP1 -? v_EIF4E +v_MEK_i -? v_ERK_i +v_AKT_i -? v_ESR1 +v_ES -? v_ESR1 +v_FOXO3 -? v_ESR1 +v_KMT2D -? v_ESR1 +v_PGR -? v_ESR1 +v_FAS -? v_FADD +v_TRADD -? v_FADD +v_AKT_i -? v_FAS +v_FASLG -? v_FAS +v_P53 -? v_FAS +v_FASLG -? v_FASLG +v_FOXO3 -? v_FASLG +v_P53 -? v_FASLG +v_AKT_i -? v_FOXO1 +v_SGK1 -? v_FOXO1 +v_AKT_i -? v_FOXO3 +v_CREB1 -? v_FZD3 +v_WNT1 -? v_FZD3 +v_STAT1 -? v_GATA3 +v_EGFR -? v_GRB2 +v_IRS1 -? v_GRB2 +v_LATS1 -? v_GRB2 +v_SRC -? v_GRB2 +v_INSR -? v_GRB7 +v_PRKACA -? v_GRB7 +v_AKT_i -? v_GSK3B +v_ERK_i -? v_GSK3B +v_EGF -? v_HER2 +v_HER3 -? v_HER2 +v_HER2 -? v_HER3 +v_NRG1 -? v_HER3 +v_NCID -? v_HES1 +v_NCID -? v_HEY1 +v_IGF1 -? v_HRAS +v_NF1 -? v_HRAS +v_PIP3 -? v_HRAS +v_SOS1 -? v_HRAS +v_PDPK1 -? v_HSP90AA1 +v_ESR1 -? v_IGF1R +v_FOXO3 -? v_IGF1R +v_IGF1 -? v_IGF1R +v_INS -? v_IGF1R +v_SRC -? v_IGF1R +v_NOS3 -? v_IL1B +v_RELA -? v_IL1B +v_IL1B -? v_IL6 +v_IL6 -? v_IL6 +v_IL6 -? v_IL6R +v_STAT5 -? v_IL8 +v_FOXO3 -? v_INSR +v_INS -? v_INSR +v_IGF1R -? v_IRS1 +v_INSR -? v_IRS1 +v_S6K1 -? v_IRS1 +v_MTORC1_c -? v_IVEBP1 +v_ABL1 -? v_JAK2 +v_IL6R -? v_JAK2 +v_IL8 -? v_JAK2 +v_IRS1 -? v_JAK2 +v_ERK_i -? v_JUN +v_MAPK8 -? v_JUN +v_PPARG -? v_JUN +v_RELA -? v_JUN +v_AKT_i -? v_KMT2D +v_PAX7 -? v_KMT2D +v_EGFR -? v_KRT14 +v_PAK2 -? v_KRT14 +v_LCK -? v_LATS1 +v_NF2 -? v_LATS1 +v_AKT_i -? v_LCK +v_ERK_i -? v_LCK +v_RAC1 -? v_MAPK8 +v_RND1 -? v_MAPK8 +v_ERK_i -? v_MCL1 +v_GSK3B -? v_MCL1 +v_AKT_i -? v_MDM2 +v_P53 -? v_MDM2 +v_RAF1 -? v_MEK_i +v_IGF1 -? v_MTORC1_c +v_NRG1 -? v_MTORC1_c +v_PIM -? v_MTORC1_c +v_RHEB -? v_MTORC1_c +v_PIP3 -? v_MTORC2_c +v_S6K1 -? v_MTORC2_c +v_CTNNB1 -? v_MYC +v_EIF4E -? v_MYC +v_ERK_i -? v_MYC +v_ESR1 -? v_MYC +v_FOXO3 -? v_MYC +v_GSK3B -? v_MYC +v_IGF1 -? v_MYC +v_KMT2D -? v_MYC +v_NRG1 -? v_MYC +v_PIM -? v_MYC +v_STAT3 -? v_MYC +v_ABL1 -? v_MYOD1 +v_HES1 -? v_MYOD1 +v_HEY1 -? v_MYOG +v_MYOD1 -? v_MYOG +v_NOTCH1 -? v_NCID +v_PRKACA -? v_NEDD4L +v_SGK1 -? v_NEDD4L +v_P53 -? v_NF1 +v_TWIST1 -? v_NF1 +v_NEDD4L -? v_NF2 +v_NOTCH1 -? v_NFKB1 +v_AKT_i -? v_NOS3 +v_HSP90AA1 -? v_NOS3 +v_CTNNB1 -? v_NOTCH1 +v_DLL_i -? v_NOTCH1 +v_LCK -? v_NOTCH1 +v_MDM2 -? v_NOTCH1 +v_AKT_i -? v_P21 +v_ERK_i -? v_P21 +v_MYC -? v_P21 +v_MDM2 -? v_P53 +v_TCF4 -? v_PAK1 +v_RAC1 -? v_PAK2 +v_SRC -? v_PAK2 +v_HES1 -? v_PAX7 +v_HEY1 -? v_PAX7 +v_MYOG -? v_PAX7 +v_NOTCH1 -? v_PAX7 +v_IGF1R -? v_PDPK1 +v_PIP3 -? v_PDPK1 +v_ERK_i -? v_PGR +v_ESR1 -? v_PGR +v_PG -? v_PGR +v_EGFR -? v_PI3K_c +v_ESR1 -? v_PI3K_c +v_IGF1R -? v_PI3K_c +v_INSR -? v_PI3K_c +v_IRS1 -? v_PI3K_c +v_RAS_i -? v_PI3K_c +v_STAT5 -? v_PIM +v_PI3K_c -? v_PIP3 +v_PTEN -? v_PIP3 +v_CEBPB -? v_PPARG +v_GATA3 -? v_PPARG +v_CYCLIN_D_c -? v_PRB +v_PRKACA -? v_PRKAA2 +v_STK11 -? v_PRKAA2 +v_AKT_i -? v_PRKACA +v_WNT1 -? v_PRKACA +v_S6K1 -? v_PTEN +v_SRC -? v_PTEN +v_AKT_i -? v_RAC1 +v_DVL1 -? v_RAC1 +v_PI3K_c -? v_RAC1 +v_HRAS -? v_RAF1 +v_RAS_i -? v_RAF1 +v_IGF1 -? v_RAS_i +v_PIP3 -? v_RAS_i +v_SOS1 -? v_RAS_i +v_NFKB1 -? v_RELA +v_PIM -? v_RELA +v_TSC2 -? v_RHEB +v_DVL1 -? v_RND1 +v_GRB7 -? v_RND1 +v_MTORC1_c -? v_S6K1 +v_MTORC1_c -? v_SGK1 +v_MTORC2_c -? v_SGK1 +v_PDPK1 -? v_SGK1 +v_GRB2 -? v_SOS1 +v_ABL1 -? v_SRC +v_PRKACA -? v_SRC +v_JAK2 -? v_STAT1 +v_SRC -? v_STAT1 +v_IL1B -? v_STAT3 +v_JAK2 -? v_STAT3 +v_MAPK8 -? v_STAT3 +v_SRC -? v_STAT3 +v_EGFR -? v_STAT5 +v_JAK2 -? v_STAT5 +v_SRC -? v_STAT5 +v_ERK_i -? v_STK11 +v_CTNNB1 -? v_TCF4 +v_JUN -? v_TCF4 +v_YAP1 -? v_TEAD1 +v_KRT14 -? v_TRADD +v_AKT_i -? v_TSC2 +v_ERK_i -? v_TSC2 +v_GSK3B -? v_TSC2 +v_PRKAA2 -? v_TSC2 +v_AKT_i -? v_TWIST1 +v_ERK_i -? v_TWIST1 +v_MAPK8 -? v_TWIST1 +v_ABL1 -? v_YAP1 +v_LATS1 -? v_YAP1 +$v_ABL1: ((v_SRC & v_GRB2) & !v_PRB) +$v_ABL2: v_ABL1 +$v_AKT_i: ((((v_MTORC2_c & v_PDPK1) & v_PIP3) & (v_IRS1 & v_IGF1R)) | (v_NRG1 | v_IGF1)) +$v_APC: v_AXIN1 +$v_AXIN1: (!v_DVL1 & v_GSK3B) +$v_BAD: !(v_PAK1 | (v_AKT_i | (v_ERK_i | v_PIM))) +$v_BAK1: (((v_BIM | v_P53) | v_BID) & !v_MCL1) +$v_BAX: (((v_BIM | v_P53) | v_BID) & !v_MCL1) +$v_BCL2: (!(v_BAD & v_BIM) | (v_CREB1 | v_ERK_i)) +$v_BCLXL: (!(v_BAD | v_BIM) & v_CREB1) +$v_BID: v_CASP8 +$v_BIM: (!(v_BCL2 & v_BCLXL) | (v_FOXO3 | v_FOXO1)) +$v_CASP3: v_CASP9 +$v_CASP8: ((v_FADD & v_NF1) & !(v_ERK_i & v_SRC)) +$v_CASP9: (((v_CYCS & v_CASP8) | v_CASP3) & !((v_ERK_i & v_PRKACA) | (v_BCLXL & v_AKT_i))) +$v_CDKN2A: (!(v_MYC | v_SRC) & v_CASP3) +$v_CEBPB: (v_ABL2 | v_CREB1) +$v_CREB1: (v_AKT_i & !v_PTEN) +$v_CTNNB1: (!v_DC & (v_WNT1 & (v_SRC & v_YAP1))) +$v_CYCLIN_D_c: (((v_TCF4 | v_TEAD1) & !(v_GSK3B | (v_CDKN2A & v_P21))) | ((v_ESR1 & (v_KMT2D & (v_FOXO3 & v_MYC))) | (v_EIF4E & (v_IGF1 | v_NRG1)))) +$v_CYCS: (v_BAK1 & v_BAX) +$v_DC: (v_APC & v_GSK3B) +$v_DVL1: (v_FZD3 & v_NF1) +$v_E2F1: !v_PRB +$v_EGFR: ((v_EGF & (v_HER2 & v_HER3)) & !v_MEK_i) +$v_EIF4E: !v_IVEBP1 +$v_ERK_i: v_MEK_i +$v_ESR1: (v_AKT_i | ((v_FOXO3 & v_KMT2D) | (v_ES & v_PGR))) +$v_FADD: (v_TRADD | v_FAS) +$v_FAS: ((v_FASLG & v_P53) & !v_AKT_i) +$v_FASLG: (v_FASLG | (v_P53 | v_FOXO3)) +$v_FOXO1: !(v_SGK1 | v_AKT_i) +$v_FOXO3: !v_AKT_i +$v_FZD3: (v_WNT1 | v_CREB1) +$v_GATA3: !v_STAT1 +$v_GRB2: (v_IRS1 | (v_LATS1 & (v_EGFR & v_SRC))) +$v_GRB7: (v_INSR & !v_PRKACA) +$v_GSK3B: !(v_AKT_i & v_ERK_i) +$v_HER2: (v_HER3 | v_EGF) +$v_HER3: (v_NRG1 | v_HER2) +$v_HES1: v_NCID +$v_HEY1: v_NCID +$v_HRAS: (((v_SOS1 | v_PIP3) & !v_NF1) | (v_PIP3 & v_IGF1)) +$v_HSP90AA1: !v_PDPK1 +$v_IGF1R: ((v_IGF1 | (v_SRC | v_INS)) | (v_FOXO3 & v_ESR1)) +$v_IL1B: (v_NOS3 & v_RELA) +$v_IL6: (v_IL1B & v_IL6) +$v_IL6R: v_IL6 +$v_IL8: v_STAT5 +$v_INSR: (v_INS | v_FOXO3) +$v_IRS1: (!v_S6K1 & (v_INSR | v_IGF1R)) +$v_IVEBP1: !v_MTORC1_c +$v_JAK2: ((v_IL6R | (v_ABL1 | v_IL8)) | v_IRS1) +$v_JUN: ((v_RELA | v_MAPK8) & (v_ERK_i & v_PPARG)) +$v_KMT2D: (v_PAX7 | !v_AKT_i) +$v_KRT14: (v_PAK2 & v_EGFR) +$v_LATS1: (v_NF2 | v_LCK) +$v_LCK: (v_ERK_i & !v_AKT_i) +$v_MAPK8: (v_RAC1 & v_RND1) +$v_MCL1: (!v_GSK3B | v_ERK_i) +$v_MDM2: (v_P53 | v_AKT_i) +$v_MEK_i: v_RAF1 +$v_MTORC1_c: ((v_PIM | v_RHEB) | (v_NRG1 | v_IGF1)) +$v_MTORC2_c: (v_PIP3 & !v_S6K1) +$v_MYC: (((v_CTNNB1 | (v_PIM | (v_ERK_i | v_STAT3))) & !v_GSK3B) | ((v_ESR1 & (v_KMT2D & v_FOXO3)) | (v_EIF4E & (v_IGF1 | v_NRG1)))) +$v_MYOD1: !(v_HES1 | v_ABL1) +$v_MYOG: (!v_HEY1 & v_MYOD1) +$v_NCID: v_NOTCH1 +$v_NEDD4L: !(v_SGK1 | v_PRKACA) +$v_NF1: (!v_TWIST1 & v_P53) +$v_NF2: v_NEDD4L +$v_NFKB1: v_NOTCH1 +$v_NOS3: (v_HSP90AA1 & v_AKT_i) +$v_NOTCH1: ((v_DLL_i & (v_CTNNB1 & v_LCK)) | v_MDM2) +$v_P21: !(v_ERK_i & (v_AKT_i & v_MYC)) +$v_P53: !v_MDM2 +$v_PAK1: v_TCF4 +$v_PAK2: (v_RAC1 & v_SRC) +$v_PAX7: (!(v_MYOG | (v_HEY1 | v_HES1)) & v_NOTCH1) +$v_PDPK1: (v_PIP3 | v_IGF1R) +$v_PGR: (v_PG & !(v_ERK_i & v_ESR1)) +$v_PI3K_c: ((v_EGFR & (v_INSR & (v_RAS_i & v_ESR1))) | (v_IRS1 & v_IGF1R)) +$v_PIM: v_STAT5 +$v_PIP3: (v_PI3K_c & !v_PTEN) +$v_PPARG: (!v_GATA3 & v_CEBPB) +$v_PRB: !v_CYCLIN_D_c +$v_PRKAA2: (v_STK11 | !v_PRKACA) +$v_PRKACA: (v_AKT_i | v_WNT1) +$v_PTEN: (v_S6K1 & !v_SRC) +$v_RAC1: ((v_PI3K_c | v_DVL1) & !v_AKT_i) +$v_RAF1: (v_HRAS | v_RAS_i) +$v_RAS_i: ((v_SOS1 & v_PIP3) | (v_PIP3 & v_IGF1)) +$v_RELA: (v_NFKB1 & v_PIM) +$v_RHEB: !v_TSC2 +$v_RND1: (v_GRB7 | v_DVL1) +$v_S6K1: v_MTORC1_c +$v_SGK1: ((v_MTORC2_c & v_MTORC1_c) & v_PDPK1) +$v_SOS1: v_GRB2 +$v_SRC: (v_PRKACA & v_ABL1) +$v_STAT1: (v_JAK2 | v_SRC) +$v_STAT3: (v_IL1B & (v_SRC & (v_MAPK8 & v_JAK2))) +$v_STAT5: (v_JAK2 & (v_SRC & v_EGFR)) +$v_STK11: !v_ERK_i +$v_TCF4: (v_CTNNB1 & v_JUN) +$v_TEAD1: v_YAP1 +$v_TRADD: !v_KRT14 +$v_TSC2: (!(v_AKT_i & v_ERK_i) | (v_PRKAA2 | v_GSK3B)) +$v_TWIST1: (v_ERK_i & (v_AKT_i & v_MAPK8)) +$v_YAP1: (!v_LATS1 & v_ABL1) diff --git a/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.bnet b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.bnet new file mode 100644 index 0000000..27e0d01 --- /dev/null +++ b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.bnet @@ -0,0 +1,110 @@ +targets,factors +v_ABL1, ((v_SRC & v_GRB2) & !v_PRB) +v_ABL2, v_ABL1 +v_AKT_i, ((((v_MTORC2_c & v_PDPK1) & v_PIP3) & (v_IRS1 & v_IGF1R)) | (v_NRG1 | v_IGF1)) +v_APC, v_AXIN1 +v_AXIN1, (!v_DVL1 & v_GSK3B) +v_BAD, !(v_PAK1 | (v_AKT_i | (v_ERK_i | v_PIM))) +v_BAK1, (((v_BIM | v_P53) | v_BID) & !v_MCL1) +v_BAX, (((v_BIM | v_P53) | v_BID) & !v_MCL1) +v_BCL2, (!(v_BAD & v_BIM) | (v_CREB1 | v_ERK_i)) +v_BCLXL, (!(v_BAD | v_BIM) & v_CREB1) +v_BID, v_CASP8 +v_BIM, (!(v_BCL2 & v_BCLXL) | (v_FOXO3 | v_FOXO1)) +v_CASP3, v_CASP9 +v_CASP8, ((v_FADD & v_NF1) & !(v_ERK_i & v_SRC)) +v_CASP9, (((v_CYCS & v_CASP8) | v_CASP3) & !((v_ERK_i & v_PRKACA) | (v_BCLXL & v_AKT_i))) +v_CDKN2A, (!(v_MYC | v_SRC) & v_CASP3) +v_CEBPB, (v_ABL2 | v_CREB1) +v_CREB1, (v_AKT_i & !v_PTEN) +v_CTNNB1, (!v_DC & (v_WNT1 & (v_SRC & v_YAP1))) +v_CYCLIN_D_c, (((v_TCF4 | v_TEAD1) & !(v_GSK3B | (v_CDKN2A & v_P21))) | ((v_ESR1 & (v_KMT2D & (v_FOXO3 & v_MYC))) | (v_EIF4E & (v_IGF1 | v_NRG1)))) +v_CYCS, (v_BAK1 & v_BAX) +v_DC, (v_APC & v_GSK3B) +v_DVL1, (v_FZD3 & v_NF1) +v_E2F1, !v_PRB +v_EGFR, ((v_EGF & (v_HER2 & v_HER3)) & !v_MEK_i) +v_EIF4E, !v_IVEBP1 +v_ERK_i, v_MEK_i +v_ESR1, (v_AKT_i | ((v_FOXO3 & v_KMT2D) | (v_ES & v_PGR))) +v_FADD, (v_TRADD | v_FAS) +v_FAS, ((v_FASLG & v_P53) & !v_AKT_i) +v_FASLG, (v_FASLG | (v_P53 | v_FOXO3)) +v_FOXO1, !(v_SGK1 | v_AKT_i) +v_FOXO3, !v_AKT_i +v_FZD3, (v_WNT1 | v_CREB1) +v_GATA3, !v_STAT1 +v_GRB2, (v_IRS1 | (v_LATS1 & (v_EGFR & v_SRC))) +v_GRB7, (v_INSR & !v_PRKACA) +v_GSK3B, !(v_AKT_i & v_ERK_i) +v_HER2, (v_HER3 | v_EGF) +v_HER3, (v_NRG1 | v_HER2) +v_HES1, v_NCID +v_HEY1, v_NCID +v_HRAS, (((v_SOS1 | v_PIP3) & !v_NF1) | (v_PIP3 & v_IGF1)) +v_HSP90AA1, !v_PDPK1 +v_IGF1R, ((v_IGF1 | (v_SRC | v_INS)) | (v_FOXO3 & v_ESR1)) +v_IL1B, (v_NOS3 & v_RELA) +v_IL6, (v_IL1B & v_IL6) +v_IL6R, v_IL6 +v_IL8, v_STAT5 +v_INSR, (v_INS | v_FOXO3) +v_IRS1, (!v_S6K1 & (v_INSR | v_IGF1R)) +v_IVEBP1, !v_MTORC1_c +v_JAK2, ((v_IL6R | (v_ABL1 | v_IL8)) | v_IRS1) +v_JUN, ((v_RELA | v_MAPK8) & (v_ERK_i & v_PPARG)) +v_KMT2D, (v_PAX7 | !v_AKT_i) +v_KRT14, (v_PAK2 & v_EGFR) +v_LATS1, (v_NF2 | v_LCK) +v_LCK, (v_ERK_i & !v_AKT_i) +v_MAPK8, (v_RAC1 & v_RND1) +v_MCL1, (!v_GSK3B | v_ERK_i) +v_MDM2, (v_P53 | v_AKT_i) +v_MEK_i, v_RAF1 +v_MTORC1_c, ((v_PIM | v_RHEB) | (v_NRG1 | v_IGF1)) +v_MTORC2_c, (v_PIP3 & !v_S6K1) +v_MYC, (((v_CTNNB1 | (v_PIM | (v_ERK_i | v_STAT3))) & !v_GSK3B) | ((v_ESR1 & (v_KMT2D & v_FOXO3)) | (v_EIF4E & (v_IGF1 | v_NRG1)))) +v_MYOD1, !(v_HES1 | v_ABL1) +v_MYOG, (!v_HEY1 & v_MYOD1) +v_NCID, v_NOTCH1 +v_NEDD4L, !(v_SGK1 | v_PRKACA) +v_NF1, (!v_TWIST1 & v_P53) +v_NF2, v_NEDD4L +v_NFKB1, v_NOTCH1 +v_NOS3, (v_HSP90AA1 & v_AKT_i) +v_NOTCH1, ((v_DLL_i & (v_CTNNB1 & v_LCK)) | v_MDM2) +v_P21, !(v_ERK_i & (v_AKT_i & v_MYC)) +v_P53, !v_MDM2 +v_PAK1, v_TCF4 +v_PAK2, (v_RAC1 & v_SRC) +v_PAX7, (!(v_MYOG | (v_HEY1 | v_HES1)) & v_NOTCH1) +v_PDPK1, (v_PIP3 | v_IGF1R) +v_PGR, (v_PG & !(v_ERK_i & v_ESR1)) +v_PI3K_c, ((v_EGFR & (v_INSR & (v_RAS_i & v_ESR1))) | (v_IRS1 & v_IGF1R)) +v_PIM, v_STAT5 +v_PIP3, (v_PI3K_c & !v_PTEN) +v_PPARG, (!v_GATA3 & v_CEBPB) +v_PRB, !v_CYCLIN_D_c +v_PRKAA2, (v_STK11 | !v_PRKACA) +v_PRKACA, (v_AKT_i | v_WNT1) +v_PTEN, (v_S6K1 & !v_SRC) +v_RAC1, ((v_PI3K_c | v_DVL1) & !v_AKT_i) +v_RAF1, (v_HRAS | v_RAS_i) +v_RAS_i, ((v_SOS1 & v_PIP3) | (v_PIP3 & v_IGF1)) +v_RELA, (v_NFKB1 & v_PIM) +v_RHEB, !v_TSC2 +v_RND1, (v_GRB7 | v_DVL1) +v_S6K1, v_MTORC1_c +v_SGK1, ((v_MTORC2_c & v_MTORC1_c) & v_PDPK1) +v_SOS1, v_GRB2 +v_SRC, (v_PRKACA & v_ABL1) +v_STAT1, (v_JAK2 | v_SRC) +v_STAT3, (v_IL1B & (v_SRC & (v_MAPK8 & v_JAK2))) +v_STAT5, (v_JAK2 & (v_SRC & v_EGFR)) +v_STK11, !v_ERK_i +v_TCF4, (v_CTNNB1 & v_JUN) +v_TEAD1, v_YAP1 +v_TRADD, !v_KRT14 +v_TSC2, (!(v_AKT_i & v_ERK_i) | (v_PRKAA2 | v_GSK3B)) +v_TWIST1, (v_ERK_i & (v_AKT_i & v_MAPK8)) +v_YAP1, (!v_LATS1 & v_ABL1) diff --git a/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.sbml b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.sbml new file mode 100644 index 0000000..7015c75 --- /dev/null +++ b/models/[id-232]__[var-109]__[in-8]__[BREAST-CANCER-PATHWAYS-MCF7-COMPLETE]/model.sbml @@ -0,0 +1 @@ +v_SRC1v_GRB21v_PRB1v_ABL11v_MTORC2_c1v_PDPK11v_PIP31v_IRS11v_IGF1R1v_NRG11v_IGF11v_AXIN11v_DVL11v_GSK3B1v_PAK11v_AKT_i1v_ERK_i1v_PIM1v_BIM1v_P531v_BID1v_MCL11v_BIM1v_P531v_BID1v_MCL11v_BAD1v_BIM1v_CREB11v_ERK_i1v_BAD1v_BIM1v_CREB11v_CASP81v_BCL21v_BCLXL1v_FOXO31v_FOXO11v_CASP91v_FADD1v_NF11v_ERK_i1v_SRC1v_CYCS1v_CASP81v_CASP31v_ERK_i1v_PRKACA1v_BCLXL1v_AKT_i1v_MYC1v_SRC1v_CASP31v_ABL21v_CREB11v_AKT_i1v_PTEN1v_DC1v_WNT11v_SRC1v_YAP11v_TCF41v_TEAD11v_GSK3B1v_CDKN2A1v_P211v_ESR11v_KMT2D1v_FOXO31v_MYC1v_EIF4E1v_IGF11v_NRG11v_BAK11v_BAX1v_APC1v_GSK3B1v_FZD31v_NF11v_PRB1v_EGF1v_HER21v_HER31v_MEK_i1v_IVEBP11v_MEK_i1v_AKT_i1v_FOXO31v_KMT2D1v_ES1v_PGR1v_TRADD1v_FAS1v_FASLG1v_P531v_AKT_i1v_FASLG1v_P531v_FOXO31v_SGK11v_AKT_i1v_AKT_i1v_WNT11v_CREB11v_STAT11v_IRS11v_LATS11v_EGFR1v_SRC1v_INSR1v_PRKACA1v_AKT_i1v_ERK_i1v_HER31v_EGF1v_NRG11v_HER21v_NCID1v_NCID1v_SOS11v_PIP31v_NF11v_PIP31v_IGF11v_PDPK11v_IGF11v_SRC1v_INS1v_FOXO31v_ESR11v_NOS31v_RELA1v_IL1B1v_IL61v_IL61v_STAT51v_INS1v_FOXO31v_S6K11v_INSR1v_IGF1R1v_MTORC1_c1v_IL6R1v_ABL11v_IL81v_IRS11v_RELA1v_MAPK81v_ERK_i1v_PPARG1v_PAX71v_AKT_i1v_PAK21v_EGFR1v_NF21v_LCK1v_ERK_i1v_AKT_i1v_RAC11v_RND11v_GSK3B1v_ERK_i1v_P531v_AKT_i1v_RAF11v_PIM1v_RHEB1v_NRG11v_IGF11v_PIP31v_S6K11v_CTNNB11v_PIM1v_ERK_i1v_STAT31v_GSK3B1v_ESR11v_KMT2D1v_FOXO31v_EIF4E1v_IGF11v_NRG11v_HES11v_ABL11v_HEY11v_MYOD11v_NOTCH11v_SGK11v_PRKACA1v_TWIST11v_P531v_NEDD4L1v_NOTCH11v_HSP90AA11v_AKT_i1v_DLL_i1v_CTNNB11v_LCK1v_MDM21v_ERK_i1v_AKT_i1v_MYC1v_MDM21v_TCF41v_RAC11v_SRC1v_MYOG1v_HEY11v_HES11v_NOTCH11v_PIP31v_IGF1R1v_PG1v_ERK_i1v_ESR11v_EGFR1v_INSR1v_RAS_i1v_ESR11v_IRS11v_IGF1R1v_STAT51v_PI3K_c1v_PTEN1v_GATA31v_CEBPB1v_CYCLIN_D_c1v_STK111v_PRKACA1v_AKT_i1v_WNT11v_S6K11v_SRC1v_PI3K_c1v_DVL11v_AKT_i1v_HRAS1v_RAS_i1v_SOS11v_PIP31v_PIP31v_IGF11v_NFKB11v_PIM1v_TSC21v_GRB71v_DVL11v_MTORC1_c1v_MTORC2_c1v_MTORC1_c1v_PDPK11v_GRB21v_PRKACA1v_ABL11v_JAK21v_SRC1v_IL1B1v_SRC1v_MAPK81v_JAK21v_JAK21v_SRC1v_EGFR1v_ERK_i1v_CTNNB11v_JUN1v_YAP11v_KRT141v_AKT_i1v_ERK_i1v_PRKAA21v_GSK3B1v_ERK_i1v_AKT_i1v_MAPK81v_LATS11v_ABL11 \ No newline at end of file diff --git a/report/.~lock.online_only_table_1.xlsx# b/report/.~lock.online_only_table_1.xlsx# deleted file mode 100644 index fc36eaf..0000000 --- a/report/.~lock.online_only_table_1.xlsx# +++ /dev/null @@ -1 +0,0 @@ -,natalie,natalie-IdeaPad-5-Pro-14ITL6,21.09.2024 20:21,file:///home/natalie/.config/libreoffice/4; \ No newline at end of file diff --git a/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/citation.bib b/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/citation.bib new file mode 100644 index 0000000..e728dfa --- /dev/null +++ b/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/citation.bib @@ -0,0 +1,8 @@ +@article{bbm-232, + author = {Taoma, Kittisak and Ruengjitchatchawalya, Marasri and Liangruksa, Monrudee and Laomettachit, Teeraphan}, + year = {2024}, + doi = {https://doi.org/10.1371/journal.pone.0298788}, + title = {Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy}, + publisher = {PLOS ONE} +} + diff --git a/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/metadata.json b/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/metadata.json new file mode 100644 index 0000000..73a1729 --- /dev/null +++ b/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/metadata.json @@ -0,0 +1,7 @@ +{ + "id": 232, + "name": "BREAST-CANCER-PATHWAYS-MCF7-COMPLETE", + "url-publication": "https://doi.org/10.1371/journal.pone.0298788", + "url-model": "https://github.com/Ktaoma/BoolSyn", + "keywords": ["source (?)","curated (?)","repaired (?)", "multi-valued (?)"] +} diff --git a/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/notes.md b/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/notes.md new file mode 100644 index 0000000..370048f --- /dev/null +++ b/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/notes.md @@ -0,0 +1,11 @@ +### Modifications + +Removed regulations: +WNT1, WNT1 +PG, PG +NRG1, NRG1 +DLL_i, DLL_i +EGF, EGF +ES, ES +IGF1, IGF1 +INS, INS diff --git a/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/source.bnet b/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/source.bnet new file mode 100644 index 0000000..83c1c01 --- /dev/null +++ b/sources/232_BREAST-CANCER-PATHWAYS-MCF7-COMPLETE/source.bnet @@ -0,0 +1,110 @@ +IL6, IL1B & IL6 +IL6R, IL6 +JAK2, (IL6R | ABL1 | IL8) | IRS1 +STAT5, JAK2 & SRC & EGFR +IL8, STAT5 +PIM, STAT5 +STAT3, IL1B & SRC & MAPK8 & JAK2 +STAT1, JAK2 | SRC +GATA3, !STAT1 +PPARG, !GATA3 & CEBPB +FZD3, WNT1 | CREB1 +DVL1, FZD3 & NF1 +AXIN1, !DVL1 & GSK3B +APC, AXIN1 +DC, APC & GSK3B +CTNNB1, !DC & (WNT1 & SRC & YAP1) +TCF4, CTNNB1 & JUN +PAK1, TCF4 +NOTCH1, (DLL_i & CTNNB1 & LCK) | MDM2 +NFKB1, NOTCH1 +RELA, NFKB1 & PIM +JUN, (RELA | MAPK8) & (ERK_i & PPARG) +NCID, NOTCH1 +HES1, NCID +HEY1, NCID +MYOD1, !(HES1 | ABL1) +MYOG, !HEY1 & MYOD1 +PAX7, !(MYOG | HEY1 | HES1) & NOTCH1 +KMT2D, PAX7 | !AKT_i +IGF1R, (IGF1 | SRC | INS) | (FOXO3 & ESR1) +HER3, NRG1 | HER2 +HER2, HER3 | EGF +PGR, PG & !(ERK_i & ESR1) +ESR1, AKT_i | (FOXO3 & KMT2D) | (ES & PGR) +EGFR, (EGF & (HER2 & HER3)) & !MEK_i +GRB2, IRS1 | (LATS1 & (EGFR & SRC)) +SOS1, GRB2 +HRAS, ((SOS1 | PIP3) & !NF1) | (PIP3 & IGF1) +RAS_i, (SOS1 & PIP3) | (PIP3 & IGF1) +RAF1, (HRAS | RAS_i) +MEK_i, RAF1 +ERK_i, MEK_i +LCK, ERK_i & !AKT_i +TWIST1, ERK_i & AKT_i & MAPK8 +NF1, !TWIST1 & P53 +PI3K_c, (EGFR & INSR & RAS_i & ESR1) | (IRS1 & IGF1R ) +PTEN, S6K1 & !SRC +PIP3, PI3K_c & !PTEN +PDPK1, PIP3 | IGF1R +MTORC2_c, PIP3 & !S6K1 +AKT_i, (((MTORC2_c & PDPK1) & PIP3) & (IRS1 & IGF1R)) | (NRG1 | IGF1) +FOXO3, !AKT_i +FOXO1, !(SGK1 | AKT_i) +CREB1, AKT_i & !PTEN +GSK3B, !(AKT_i & ERK_i) +TSC2, !(AKT_i & ERK_i) | (PRKAA2 | GSK3B) +RHEB, !TSC2 +MTORC1_c, (PIM | RHEB) | (NRG1 | IGF1) +S6K1, MTORC1_c +IRS1, !S6K1 & (INSR | IGF1R) +SGK1, (MTORC2_c & MTORC1_c) & PDPK1 +NEDD4L, !(SGK1 | PRKACA) +NF2, NEDD4L +LATS1, NF2 | LCK +YAP1, !LATS1 & ABL1 +TEAD1, YAP1 +IVEBP1, !MTORC1_c +EIF4E, !IVEBP1 +MYC, (((CTNNB1 | PIM | ERK_i | STAT3) & !GSK3B) | ((ESR1 & KMT2D & FOXO3 ) | (EIF4E & (IGF1 | NRG1)))) +P21, !(ERK_i & AKT_i & MYC) +CYCLIN_D_c, ((TCF4 | TEAD1) & !(GSK3B | (CDKN2A & P21))) | ((ESR1 & KMT2D & FOXO3 & MYC ) | (EIF4E & (IGF1 | NRG1))) +PRB, !CYCLIN_D_c +E2F1, !PRB +P53, !MDM2 +MDM2, P53 | AKT_i +MCL1, !GSK3B | ERK_i +BAD, !( PAK1 | AKT_i | ERK_i | PIM) +BCL2, !(BAD & BIM) | (CREB1 | ERK_i) +BCLXL, !(BAD | BIM) & CREB1 +BIM, !(BCL2 & BCLXL) | (FOXO3 | FOXO1) +BID, CASP8 +BAK1, ((BIM | P53) | BID) & !MCL1 +BAX, ((BIM | P53) | BID) & !MCL1 +CYCS, BAK1 & BAX +CASP9, ((CYCS & CASP8) | CASP3) & !((ERK_i & PRKACA) | (BCLXL & AKT_i)) +CASP3, CASP9 +HSP90AA1, !PDPK1 +NOS3, HSP90AA1 & AKT_i +IL1B, NOS3 & RELA +STK11, !ERK_i +PRKAA2, STK11 | !PRKACA +PAK2, RAC1 & SRC +KRT14, PAK2 & EGFR +TRADD, !KRT14 +FASLG, FASLG | P53 | FOXO3 +FAS, (FASLG & P53) & !AKT_i +FADD, TRADD | FAS +CASP8, (FADD & NF1) & !(ERK_i & SRC) +PRKACA, AKT_i | WNT1 +SRC, PRKACA & ABL1 +ABL1, (SRC & GRB2) & !PRB +ABL2, ABL1 +CEBPB, ABL2 | CREB1 +CDKN2A, !(MYC | SRC) & CASP3 +INSR, INS | FOXO3 +GRB7, INSR & !PRKACA +RND1, GRB7 | DVL1 +RAC1, (PI3K_c | DVL1) & !AKT_i +MAPK8, RAC1 & RND1 +