ICD_ExtendDy.bnd

Node Tumor {
	rate_up = 0.0;
	rate_down = 0.0;
}

Node ChemoT {
    rate_up = 0.0;
    rate_down = $degChemo;
}

Node DyingTumor {
    rate_up = (Tumor & ChemoT) ? $effectChemo : 0.0 ;
    rate_down = 0.0 ;
}

Node DC {
	rate_up = 0.0;
	rate_down = 0.0;
}

Node cd4 {
	rate_up = 0.0;
	rate_down = 0.0;
}

Node cd8 {
	rate_up = 0.0;
	rate_down = 0.0;
}

Node aDC {
	logic = (DC &  P2X7R);
	rate_up = @logic ? $u_aDC : 0.0;
	rate_down = 0.0;
}
Node cd4_Act {
	logic = (( IL2_rec | IL4_rec | (CD28 & TCR_II)) & cd4);
	rate_up = @logic ? $u_cd4_Act : 0.0;
	rate_down = @logic ? 0.0 : 0.0; // no activation stop stop 
}

Node P2Y2R {
	logic = (DC);
	rate_up = @logic ? $u_P2Y2R : 0.0;
	rate_down = 0.0;
}

Node P2X7R {

	logic = (DC & P2Y2R);
	rate_up = @logic ? $u_P2X7R : 0.0;
	rate_down = 0.0;
}

Node FPR1 {

	logic = (aDC);
	rate_up = @logic ? $u_FPR1 : 0.0;
	rate_down = 0.0;
}

Node LRP1 {

	logic = (DC & FPR1);
	rate_up = @logic ? $u_LRP1 : 0.0;
	rate_down = 0.0;
}

Node TLR4 {
	logic = (aDC & LRP1 & FPR1);
	rate_up = @logic ? $u_TLR4 : 0.0;
	rate_down = 0.0;
}

Node IFN1_rec {
	logic = (Tumor); // keep Tumor instead of DyingTumor?
	rate_up = @logic ? $u_IFN1_rec : 0.0;
	rate_down = 0.0;
}

Node IL1B_rec {

	logic = (cd4);
	rate_up = @logic ? $u_IL1B_rec : 0.0;
	rate_down = @logic ? 0.0 : 0.0;
}

Node IL2_rec {

	logic = (cd8) | (cd4);
	rate_up = @logic ? $u_IL2_rec : 0.0;
	rate_down = @logic ? 0.0 : 0.0;
}

Node IL4_rec {

	logic = cd4 | Th2;
	rate_up = @logic ? $u_IL4_rec : 0.0;
	rate_down = @logic ? 0.0 : $d_IL4_rec;
}

Node IL6_rec {

	logic = cd4 | Th17;
	rate_up = @logic ? $u_IL6_rec : 0.0;
	rate_down = @logic ? 0.0 : $d_IL6_rec;
}

Node IL12_rec {

	logic = (cd4 & !cd8) | (Th1 & !cd8);
	rate_up = @logic ? $u_IL12_rec : 0.0;
	rate_down = @logic ? 0.0 : $d_IL12_rec;
}

Node IFNg_rec {

	logic = ((cd8 & !cd4)|(!cd8 & cd4));
	rate_up = @logic ? $u_IFNg_rec : 0.0;
	rate_down = @logic ? 0.0 : $d_IFNg_rec;
}

Node IL17_rec {

	logic = (cd4 | CTL);
	rate_up = @logic ? $u_IL17_rec : 0.0;
	rate_down = @logic ? 0.0 : $d_IL17_rec;
}

Node TGFb_rec {

	logic = (cd4);
	rate_up = @logic ? $u_TGFb_rec : 0.0;
	rate_down = @logic ? 0.0 : $d_TGFb_rec;
}

Node CXCR3 {

	logic = ((!cd4 & cd8) | (cd4 & !cd8)) | (CXCR3);
	rate_up = @logic ? $u_CXCR3 : 0.0;
	rate_down = 0.0;
}


Node CD28 {

	logic = (((!cd4 & cd8) | (cd4 & !cd8)) & CXCR3) | (CD28); 
	rate_up = @logic ? $u_CD28 : 0.0;
	rate_down = 0.0;
}

 

Node TCR_I {

	logic = (CD28 & cd8);
	rate_up = @logic ? $u_TCR_I : 0.0;
	rate_down = 0.0;
}

Node TCR_II {

	logic = (cd4 & CD28);
	rate_up = @logic ? $u_TCR_II : 0.0;
	rate_down = 0.0;
}


Node Th1 {

	logic = (cd4 & CD28 & TCR_II & IL12_rec) | Th1; //why Th1 ?
	rate_up = @logic ? $u_Th1 : 0.0;
	rate_down = 0.0;
}

Node Th2 {

	logic = (cd4 & CD28 & TCR_II & (IL4_rec | IL2_rec) & !(Th1 | Th17 | Treg)) | Th2; 
	rate_up = @logic ? $u_Th2 : 0.0;
	rate_down = 0.0;
}


Node Th17 {

	logic = (cd4 & CD28 & TCR_II) & (IL6_rec | IL1B_rec | TGFb_rec) & !(Th1 | Th2 | Treg) | Th17;
	rate_up = @logic ? $u_Th17 : 0.0;
	rate_down = 0.0;
}

// same mistake and same remark on Th17 self-sustaining

Node Treg {

	logic = (Treg) | ((cd4 & CD28 & TCR_II) & (TGFb_rec | IL2_rec) & !(Th1 | Th2 | Th17)); 
	rate_up = @logic ? $u_Treg : 0.0;
	rate_down = 0.0;
}

// same mistake and same remark on Treg self-sustaining

Node CALR_o {

	logic = (DyingTumor);
	rate_up = @logic ? $u_CALR_o : 0.0;
	rate_down = @logic ? 0.0 : $d_CALR_o;
}

Node ATP_o {

	logic = (DyingTumor);
	rate_up = @logic ? $u_ATP_o : 0.0;
	rate_down = @logic ? 0.0 : $d_ATP_o;
}

Node ANXA1_o {

	logic = (DyingTumor);
	rate_up = @logic ? $u_ANXA1_o : 0.0;
	rate_down = @logic ? 0.0 : $d_ANXA1_o;
}

Node HMGB1_o {

	logic = (DyingTumor & ANXA1_o);
	rate_up = @logic ? $u_HMGB1_o : 0.0;
	rate_down = @logic ? 0.0 : $d_HMGB1_o;
}

Node CXCL10_o {

	logic = (Tumor & IFN1_rec);
	rate_up = @logic ? $u_CXCL10_o : 0.0;
	rate_down = @logic ? 0.0 : $d_CXCL10_o;
}

Node CD80_o {

	logic = (aDC & TLR4 & LRP1);
	rate_up = @logic ? $u_CD80_o : 0.0;
	rate_down = @logic ? 0.0 : $d_CD80_o;
}

Node MHC_I_o {

	logic = (aDC & TLR4 & LRP1);
	rate_up = @logic ? $u_MHC_I_o : 0.0;
	rate_down = @logic ? 0.0 : $d_MHC_I_o;
}

Node MHC_II_o {

	logic = (aDC & TLR4 & LRP1);
	rate_up = @logic ? $u_MHC_II_o : 0.0;
	rate_down = @logic ? 0.0 : $d_MHC_II_o;
}

Node IL1B_o {
	
	logic = (aDC & TLR4 & LRP1);
	rate_up = @logic ? $u_IL1B_o : 0.0;
	rate_down = @logic ? 0.0 : $d_IL1B_o;
}

Node IL2_o {

	logic = ((cd4 & CD28 & TCR_II) & cd4_Act) | (Th1 & cd4_Act) | (DC & TLR4 & (TCR_II | TCR_I)) | (Th2 & cd4_Act);
	rate_up = @logic ? $u_IL2_o : 0.0;
	rate_down = @logic ? 0.0 : $d_IL2_o;
}

Node IL4_o {

	logic = (Th2 & cd4_Act) | ((cd4 & CD28 & TCR_II) & cd4_Act) | (preCTL & cd4_Act);
	rate_up = @logic ? $u_IL4_o : 0.0;
	rate_down = @logic ? 0.0 : $d_IL4_o;
}

Node IL6_o {

	logic = (aDC & TLR4 & TCR_II);
	rate_up = @logic ? $u_IL6_o : 0.0;
	rate_down = @logic ? 0.0 : $d_IL6_o;
}

Node IL12_o {

	logic = (aDC & TLR4);
	rate_up = @logic ? $u_IL12_o : 0.0;
	rate_down = @logic ? 0.0 : $d_IL12_o;
}

Node IL17_o {

	logic = (IL1B_rec & Th17 & cd4_Act);
	rate_up = @logic ? $u_IL17_o : 0.0;
	rate_down = @logic ? 0.0 : $d_IL17_o;
}

Node IFNg_o {

	logic = (IL12_rec & CTL) | (IFNg_rec & Th1 & cd4_Act) | (IL12_rec & CTL) | ((cd4 & CD28 & TCR_II) & IL12_rec & cd4_Act ) | (IL12_rec & Th1 & cd4_Act);
	rate_up = @logic ? $u_IFNg_o : 0.0;
	rate_down = @logic ? 0.0 : $d_IFNg_o;
}



Node TGFb_o {

	logic = (cd4 & cd4_Act) | (Treg & cd4_Act) | Tumor;
	rate_up = @logic ? $u_TGFb_o : 0.0;
	rate_down = @logic ? 0.0 : $d_TGFb_o;
}

Node Perforin_o {

	logic = CTL;
	rate_up = @logic ? $u_Perforin_o : 0.0;
	rate_down = (-log(1-$pop_Tumor))/$PerforinRecycled;
}


Node preCTL {

	logic = (IL2_rec & cd8 & TCR_I);
	rate_up = @logic ? $u_preCTL : 0.0;
	rate_down = 0.0;
}

Node CTL {

	logic = (!IL2_rec & IFNg_rec & preCTL) | (IL2_rec & preCTL);
	rate_up = @logic ? $u_CTL : 0.0;
	rate_down = 0 ;
}

Node IFN1_o {

	logic = (Tumor & TLR4) | (DC & TLR4);
	rate_up = @logic ? $u_IFN1_o : 0.0;
	rate_down = @logic ? 0.0 : $d_IFN1_o;
}

Node Division {


	rate_up = (Tumor? $growth_tumor : 0.0) + ((CTL & !(Perforin_o)) ? $clonal_exp_rate : 0.0);
	rate_down = 0.0;
}

Node Death {
	
	rate_up = (Tumor ? ((-log(1-$rate_perforin)*$aggressivity)+$ChemoEffect) : 0.0) + (Perforin_o ? $PerforinDeath : 0.0); //no death of CTL ?
	rate_down = 0.0;
}