{"text_format":"2","workbook":"xls","n_sheets":2,"sheets":["Figure 5 Model I Network","Figure 7 Network"],"not_rendered":{"charts":0,"images":2,"macros":0,"external_links":0,"defined_names":0,"comments":0,"pivot_tables":0},"unopened":[],"bounds":{"document_bytes":16777216,"sheet_cells":100000,"run_cost":"one","rows_first":2000,"rows_last":500,"rows_between":2000,"halvings":0,"cell_chars":16384,"cell_head_chars":4096},"cells_cut":0,"cells_raw":0,"read":"whole","date_system":"1900","formulas":"cached_only"}

{"sheet":"Figure 5 Model I Network","index":0,"n_rows":52,"n_cols":13,"rows_kept":52,"cut":false,"hidden":false,"merged":[],"flags":["formulas_cached_only"]}
[null,"Supplementary File - Excel spreadsheet for Figure 5's Model I Network"]
[null,"Each row in a truth table represents a unique input condition.  The output for each row's input, is presented in the far right shaded column."]
[null,"The number of rows in a truth table is dependent on the number of regulating nodes (r)  each node has."]
[null,"In these examples, there are only 2 possible values for each node, so there are 2r rows  in a truth table "]
[]
[]
[null,"Logic Function:",{"$nulls":9},"FIGURE 5, MODEL I"]
[null,"MYCt+1 = GrowthFactort AND NOT  OverPopt AND NOT Hypoxiat"]
[null,"GrowthF","OverPop","Hypox","MYCt+1"]
[null,0,0,0,0]
[null,0,1,0,0]
[null,0,0,1,0]
[null,0,1,1,0]
[null,1,0,0,1]
[null,1,1,0,0]
[null,1,0,1,0]
[null,1,1,1,0]
[null,"Biological Meaning of Logic Function:"]
[null,"MYC is only ON (in 1/8 conditions) when Growth Factor is active "]
[null,"AND the negative proliferative signals (Overpopulation and Hypoxia) are absent."]
[]
[null,"Logic Function:",{"$nulls":8},"Logic Function:"]
[null,"P27t+1 = Hypoxiat  OR NOT MYCt ",{"$nulls":8},"Cyc-Cdkt+1 = NOT P27t AND NOT P53t"]
[null,"Hypox","MYC","P27t+1",{"$nulls":6},"P27","P53","Cyc-Cdkt+1"]
[null,0,0,1,{"$nulls":6},0,0,1]
[null,1,0,1,{"$nulls":6},1,0,0]
[null,0,1,0,{"$nulls":6},0,1,0]
[null,1,1,1,{"$nulls":6},1,1,0]
[null,"Biological Meaning of Logic Function:",{"$nulls":8},"Biological Meaning of Logic Function:"]
[null,"P27 is only OFF when MYC is present but Hypox (and SMAD) is not.",{"$nulls":8},"Cyc-Cdk is only activated when both P27 activation and P53 activation are absent."]
[null,"All other conditions, including the absence of both regulators turns P27 on",{"$nulls":8},"The activation of just one of the two inhibitors is enough to turn off Cyc-Cdk activation."]
[]
[null,"Logic Function:",{"$nulls":8},"Logic Function:"]
[null,"P53t+1 = DNA Damaget",{"$nulls":8},"Prolift+1 =Cyc-Cdkt"]
[null,"DNA Dam","P53t+1",{"$nulls":7},"Cyc-Cdk","Prolift+1"]
[null,0,0,{"$nulls":7},0,0]
[null,1,1,{"$nulls":7},1,1]
[null,"Biological Meaning of Logic Function:",{"$nulls":8},"Biological Meaning of Logic Function:"]
[null,"P53 is only activated in the model when DNA Damage is present.",{"$nulls":8},"Proliferation only occurs in this model when functional levels of Cyc-Cdk are present"]
[{"$nulls":10},"to regulate cell cycle progression."]
[null,"Logic Function:"]
[null,"Apopt+1 =P53t"]
[null,"P53","Apopt+1"]
[null,0,0]
[null,1,1]
[null,"Biological Meaning of Logic Function:"]
[null,"Apoptosis only occurs in this model when functional levels of P53 "]
[null,"are present to mediate  programmed cell death response."]
[]
[]
["Electronic Supplementary Material (ESI) for Integrative Biology"]
["This journal is © The Royal Society of Chemistry 2012"]

{"sheet":"Figure 7 Network","index":1,"n_rows":91,"n_cols":16,"rows_kept":91,"cut":false,"hidden":false,"merged":[],"flags":["formulas_cached_only"]}
[null,"Supplementary File - Excel spreadsheet for Figure 7's Network"]
[null,"Each row in a truth table represents a unique input condition.  The output for each row's input, is presented in the far right shaded column."]
[null,"The number of rows in a truth table is dependent on the number of regulating nodes (r)  each node has."]
[null,"In these examples, there are only 2 possible values for each node, so there are 2r rows  in a truth table "]
[]
[null,"Logic Function:"]
[null,"MYCt+1 = (AKTt OR RASt) AND NOT  OverPopt AND NOT Hypoxiat",{"$nulls":10},"FIGURE 7"]
[null,"AKT","RAS","OverPop","Hypox","MYCt+1"]
[null,0,0,0,0,0]
[null,0,0,1,0,0]
[null,0,0,0,1,0]
[null,0,0,1,1,0]
[null,0,1,0,0,1]
[null,0,1,1,0,0]
[null,0,1,0,1,0]
[null,0,1,1,1,0]
[null,1,0,0,0,1]
[null,1,0,1,0,0]
[null,1,0,0,1,0]
[null,1,0,1,1,0]
[null,1,1,0,0,1]
[null,1,1,1,0,0]
[null,1,1,0,1,0]
[null,1,1,1,1,0]
[null,"Biological Meaning of Logic Function:"]
[null,"MYC is only ON (in 2/16 conditions) when proliferative signaling through "]
[null,"RAS or AKT is present AND the negative proliferative signals (Overpopulation and Hypoxia) are absent."]
[]
[null,"Logic Function:",{"$nulls":4},"Logic Function:",{"$nulls":4},"Logic Function:"]
[null,"RASt+1 = GrowthFactort  ",{"$nulls":4},"FOXOt+1 = NOT AKTt  ",{"$nulls":4},"AKTt+1 = Growth Factort AND NOT PTENt"]
[null,"Growth F","RASt+1",null,null,null,"AKT","FOXOt+1",null,null,null,"Growth F","PTEN","AKTt+1"]
[null,0,0,null,null,null,0,1,null,null,null,0,0,0]
[null,1,1,null,null,null,1,0,null,null,null,1,0,1]
[null,"Biological Meaning of Logic Function:",{"$nulls":4},"Biological Meaning of Logic Function:",{"$nulls":4},0,1,0]
[null,"RAS can only be activated by Growth Factor ",{"$nulls":4},"FOXO is active in the model unles AKT",{"$nulls":4},1,1,0]
[null,"signaling in this model",{"$nulls":4},"is activated, which allows for direct inhibition",{"$nulls":4},"Biological Meaning of Logic Function:"]
[{"$nulls":11},"AKT is only activated by Growth Factor signaling but PTEN inhibition of AKT"]
[{"$nulls":11}," is stronger than Growth Factor activation."]
[]
[null,"Logic Function:",{"$nulls":9},"Logic Function:"]
[null,"P27t+1 = FOXOt OR Hypoxiat  OR NOT MYCt ",{"$nulls":9},"Cyc-Cdkt+1 = NOT P27t AND NOT P53t",null,null,null," "]
[null,"FOXO","Hypox","MYC","P27t+1",{"$nulls":6},"P27","P53","Cyc-Cdkt+1"]
[null,0,0,0,1,{"$nulls":6},0,0,1]
[null,0,1,0,1,{"$nulls":6},1,0,0]
[null,0,0,1,0,{"$nulls":6},0,1,0]
[null,0,1,1,1,{"$nulls":6},1,1,0]
[null,1,0,0,1,{"$nulls":6},"Biological Meaning of Logic Function:"]
[null,1,1,0,1,{"$nulls":6},"Cyc-Cdk is only activated when both P27 activation and P53 activation are absent."]
[null,1,0,1,1,{"$nulls":6},"The activation of just one of the two inhibitors is enough to turn off Cyc-Cdk activation."]
[null,1,1,1,1]
[null,"Biological Meaning of Logic Function:"]
[null,"P27 is only OFF when MYC is present but Hypox (via SMAD) and FOXO are not."]
[null,"All other conditions, including the absence of all three regulators, turn P27 on."]
[]
[]
[null,"Logic Function:",{"$nulls":9},"Logic Function:"]
[null,"P53t+1 = DNA Damaget AND NOT MDM2t",{"$nulls":9},"Prolift+1 =Cyc-Cdkt"]
[null,"DNA Dam","MDM2","P53t+1",{"$nulls":7},"Cyc-Cdk","Prolift+1"]
[null,0,0,0,{"$nulls":7},0,0]
[null,1,0,1,{"$nulls":7},1,1]
[null,0,1,0,{"$nulls":7},"Biological Meaning of Logic Function:"]
[null,1,1,0,{"$nulls":7},"Proliferation only occurs in this model when functional levels of Cyc-Cdk are present"]
[null,"Biological Meaning of Logic Function:",{"$nulls":9},"to regulate cell cycle progression."]
[null,"P53 is only activated in the model when DNA Damage is present "]
[null,"and MDM2 is not."]
[]
[null,"Logic Function:",{"$nulls":4},"Logic Function:",{"$nulls":4},"Logic Function:"]
[null,"BADt+1 = NOT AKTt",{"$nulls":4},"MDM2t+1 = P53t",{"$nulls":4},"Apopt+1 = BAXt"]
[null,"AKT","BADt+1",null,null,null,"P53","MDM2t+1",null,null,null,"BAX","Apopt+1"]
[null,0,1,null,null,null,0,0,null,null,null,0,0]
[null,1,0,null,null,null,1,1,null,null,null,1,1]
[null,"Biological Meaning of Logic Function:",{"$nulls":4},"Biological Meaning of Logic Function:",{"$nulls":4},"Biological Meaning of Logic Function:"]
[null,"BAD is active in the model unles AKT",{"$nulls":4},"MDM2 can only be activated by P53",{"$nulls":4},"Apoptosis only occurs in this model when functional levels of BAX"]
[null,"is activated, which is a direct inhibitor of BAD.",{"$nulls":4},"activation in this model.",{"$nulls":4},"are present."]
[]
[]
[null,"Logic Function:"]
[null,"BAXt+1 = P53t AND BADt"]
[null,"P53","BAD","P53t+1"]
[null,0,0,0]
[null,1,0,0]
[null,0,1,0]
[null,1,1,1]
[null,"Biological Meaning of Logic Function:"]
[null,"BAX is only activated in the model when P53 and BAD are present."]
[null,"The assumption is that P53 must bind to BAD to induce activation of BAX."]
[]
[]
[]
["Electronic Supplementary Material (ESI) for Integrative Biology"]
["This journal is © The Royal Society of Chemistry 2012"]