/* There are a total of 21 entries in the algebraic variable array. There are a total of 20 entries in each of the rate and state variable arrays. There are a total of 50 entries in the constant variable array. */ /* * VOI is time in component environment (second). * ALGEBRAIC[5] is LRG in component beta_adrenergic_receptor_module (micromolar). * ALGEBRAIC[7] is RG in component beta_adrenergic_receptor_module (micromolar). * ALGEBRAIC[0] is LR in component beta_adrenergic_receptor_module (micromolar). * STATES[0] is beta1_AR in component beta_adrenergic_receptor_module (micromolar). * STATES[1] is Gs in component beta_adrenergic_receptor_module (micromolar). * STATES[2] is beta1_ARact in component beta_adrenergic_receptor_module (micromolar). * STATES[3] is beta1_AR_S464 in component beta_adrenergic_receptor_module (micromolar). * STATES[4] is beta1_AR_S301 in component beta_adrenergic_receptor_module (micromolar). * STATES[5] is L in component beta_adrenergic_receptor_module (micromolar). * CONSTANTS[0] is Ltotmax in component beta_adrenergic_receptor_module (micromolar). * CONSTANTS[1] is KL in component beta_adrenergic_receptor_module (micromolar). * CONSTANTS[2] is KR in component beta_adrenergic_receptor_module (micromolar). * CONSTANTS[3] is KC in component beta_adrenergic_receptor_module (micromolar). * CONSTANTS[4] is Gstot in component beta_adrenergic_receptor_module (micromolar). * CONSTANTS[5] is k_betaARK_plus in component beta_adrenergic_receptor_module (first_order_rate_constant). * CONSTANTS[6] is k_betaARK_minus in component beta_adrenergic_receptor_module (first_order_rate_constant). * CONSTANTS[7] is k_PKA_plus in component beta_adrenergic_receptor_module (second_order_rate_constant). * CONSTANTS[8] is k_PKA_minus in component beta_adrenergic_receptor_module (first_order_rate_constant). * STATES[6] is Gs_beta_gamma in component Gs_activation_module (micromolar). * ALGEBRAIC[9] is PKACI in component PKA_activation_module (micromolar). * STATES[7] is Gs_alpha_GTPtot in component Gs_activation_module (micromolar). * STATES[8] is Gs_alpha_GDP in component Gs_activation_module (micromolar). * CONSTANTS[9] is k_gact in component Gs_activation_module (first_order_rate_constant). * CONSTANTS[10] is k_hyd in component Gs_activation_module (first_order_rate_constant). * CONSTANTS[11] is k_reassoc in component Gs_activation_module (second_order_rate_constant). * STATES[9] is cAMPtot in component cyclic_AMP_metabolism_module (micromolar). * STATES[10] is AC in component cyclic_AMP_metabolism_module (micromolar). * STATES[11] is Gs_alpha_GTP in component cyclic_AMP_metabolism_module (micromolar). * ALGEBRAIC[2] is Gs_alpha_GTP_AC in component cyclic_AMP_metabolism_module (micromolar). * STATES[12] is PDE in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[12] is ACtot in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[13] is ATP in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[14] is PDEtot in component cyclic_AMP_metabolism_module (micromolar). * ALGEBRAIC[1] is PDEinhib in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[15] is IBMXtot in component cyclic_AMP_metabolism_module (micromolar). * STATES[13] is IBMX in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[16] is fsktot in component cyclic_AMP_metabolism_module (micromolar). * STATES[14] is fsk in component cyclic_AMP_metabolism_module (micromolar). * ALGEBRAIC[6] is fsk_AC in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[17] is kAC_basal in component cyclic_AMP_metabolism_module (first_order_rate_constant). * CONSTANTS[18] is kAC_fsk in component cyclic_AMP_metabolism_module (first_order_rate_constant). * CONSTANTS[19] is k_PDE in component cyclic_AMP_metabolism_module (first_order_rate_constant). * CONSTANTS[20] is kAC_Gs_alpha in component cyclic_AMP_metabolism_module (first_order_rate_constant). * CONSTANTS[21] is Km_basal in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[22] is Km_PDE in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[23] is Km_fsk in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[24] is K_fsk in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[25] is Km_Gs_alpha_GTP in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[26] is K_Gs_alpha in component cyclic_AMP_metabolism_module (micromolar). * CONSTANTS[27] is K_IBMX in component cyclic_AMP_metabolism_module (micromolar). * ALGEBRAIC[10] is cAMP in component PKA_activation_module (micromolar). * ALGEBRAIC[11] is PKACII in component PKA_activation_module (micromolar). * ALGEBRAIC[12] is PKAtemp in component PKA_activation_module (micromolar). * ALGEBRAIC[13] is ARCI in component PKA_activation_module (micromolar). * ALGEBRAIC[14] is A2RCI in component PKA_activation_module (micromolar). * ALGEBRAIC[15] is A2RI in component PKA_activation_module (micromolar). * ALGEBRAIC[16] is A2RCII in component PKA_activation_module (micromolar). * ALGEBRAIC[17] is A2RII in component PKA_activation_module (micromolar). * ALGEBRAIC[18] is ARCII in component PKA_activation_module (micromolar). * CONSTANTS[28] is Ki_pki in component PKA_activation_module (micromolar). * CONSTANTS[29] is PKAItot in component PKA_activation_module (micromolar). * CONSTANTS[30] is PKAIItot in component PKA_activation_module (micromolar). * CONSTANTS[31] is PKItot in component PKA_activation_module (micromolar). * CONSTANTS[32] is KA in component PKA_activation_module (micromolar). * CONSTANTS[33] is KB in component PKA_activation_module (micromolar). * CONSTANTS[34] is KD in component PKA_activation_module (micromolar). * CONSTANTS[35] is KPKI in component PKA_activation_module (micromolar). * ALGEBRAIC[19] is PKI in component PKA_activation_module (micromolar). * ALGEBRAIC[3] is fracPLBp in component phospholamban_regulation_module (dimensionless). * ALGEBRAIC[20] is fracPLB in component phospholamban_regulation_module (dimensionless). * CONSTANTS[36] is fracPLBo in component phospholamban_regulation_module (dimensionless). * STATES[15] is PLBp in component phospholamban_regulation_module (micromolar). * ALGEBRAIC[8] is PLB in component phospholamban_regulation_module (micromolar). * STATES[16] is Inhib1ptot in component phospholamban_regulation_module (micromolar). * STATES[17] is Inhib1 in component phospholamban_regulation_module (micromolar). * STATES[18] is Inhib1p in component phospholamban_regulation_module (micromolar). * ALGEBRAIC[4] is PP1_Inhib1p in component phospholamban_regulation_module (micromolar). * STATES[19] is PP1 in component phospholamban_regulation_module (micromolar). * CONSTANTS[37] is PP1tot in component phospholamban_regulation_module (micromolar). * CONSTANTS[38] is PLBtot in component phospholamban_regulation_module (micromolar). * CONSTANTS[39] is Inhib1tot in component phospholamban_regulation_module (micromolar). * CONSTANTS[40] is epsilon in component phospholamban_regulation_module (dimensionless). * CONSTANTS[41] is kPKA_PLB in component phospholamban_regulation_module (first_order_rate_constant). * CONSTANTS[42] is KmPKA_PLB in component phospholamban_regulation_module (micromolar). * CONSTANTS[43] is kPKA_Inhib1 in component phospholamban_regulation_module (first_order_rate_constant). * CONSTANTS[44] is kPP1_PLB in component phospholamban_regulation_module (first_order_rate_constant). * CONSTANTS[45] is KmPP1_PLB in component phospholamban_regulation_module (micromolar). * CONSTANTS[46] is KmPKA_Inhib1 in component phospholamban_regulation_module (micromolar). * CONSTANTS[47] is VmaxPP2A_Inhib1 in component phospholamban_regulation_module (flux). * CONSTANTS[48] is KmPP2A_Inhib1 in component phospholamban_regulation_module (micromolar). * CONSTANTS[49] is KInhib1 in component phospholamban_regulation_module (micromolar). * RATES[5] is d/dt L in component beta_adrenergic_receptor_module (micromolar). * RATES[1] is d/dt Gs in component beta_adrenergic_receptor_module (micromolar). * RATES[0] is d/dt beta1_AR in component beta_adrenergic_receptor_module (micromolar). * RATES[2] is d/dt beta1_ARact in component beta_adrenergic_receptor_module (micromolar). * RATES[3] is d/dt beta1_AR_S464 in component beta_adrenergic_receptor_module (micromolar). * RATES[4] is d/dt beta1_AR_S301 in component beta_adrenergic_receptor_module (micromolar). * RATES[7] is d/dt Gs_alpha_GTPtot in component Gs_activation_module (micromolar). * RATES[6] is d/dt Gs_beta_gamma in component Gs_activation_module (micromolar). * RATES[8] is d/dt Gs_alpha_GDP in component Gs_activation_module (micromolar). * RATES[11] is d/dt Gs_alpha_GTP in component cyclic_AMP_metabolism_module (micromolar). * RATES[14] is d/dt fsk in component cyclic_AMP_metabolism_module (micromolar). * RATES[10] is d/dt AC in component cyclic_AMP_metabolism_module (micromolar). * RATES[12] is d/dt PDE in component cyclic_AMP_metabolism_module (micromolar). * RATES[13] is d/dt IBMX in component cyclic_AMP_metabolism_module (micromolar). * RATES[9] is d/dt cAMPtot in component cyclic_AMP_metabolism_module (micromolar). * RATES[19] is d/dt PP1 in component phospholamban_regulation_module (micromolar). * RATES[18] is d/dt Inhib1p in component phospholamban_regulation_module (micromolar). * RATES[15] is d/dt PLBp in component phospholamban_regulation_module (micromolar). * RATES[16] is d/dt Inhib1ptot in component phospholamban_regulation_module (micromolar). * RATES[17] is d/dt Inhib1 in component phospholamban_regulation_module (micromolar). */ void initConsts(double* CONSTANTS, double* RATES, double *STATES) { STATES[0] = 0.0001; STATES[1] = 3.182; STATES[2] = 0.01205; STATES[3] = 0; STATES[4] = 1.154e-3; STATES[5] = 0.988; CONSTANTS[0] = 1; CONSTANTS[1] = 0.285; CONSTANTS[2] = 0.062; CONSTANTS[3] = 33; CONSTANTS[4] = 3.83; CONSTANTS[5] = 1.1e-3; CONSTANTS[6] = 2.2e-3; CONSTANTS[7] = 3.6e-3; CONSTANTS[8] = 2.2e-3; STATES[6] = 0.02569; STATES[7] = 0.02505; STATES[8] = 6.44e-4; CONSTANTS[9] = 16; CONSTANTS[10] = 0.8; CONSTANTS[11] = 1.21e3; STATES[9] = 0.8453; STATES[10] = 0.04706295; STATES[11] = 0.02241295; STATES[12] = 0.0389; CONSTANTS[12] = 49.7e-3; CONSTANTS[13] = 5e3; CONSTANTS[14] = 38.9e-3; CONSTANTS[15] = 0; STATES[13] = 0; CONSTANTS[16] = 0; STATES[14] = 0; CONSTANTS[17] = 0.2; CONSTANTS[18] = 7.3; CONSTANTS[19] = 5; CONSTANTS[20] = 8.5; CONSTANTS[21] = 1.03e3; CONSTANTS[22] = 1.3; CONSTANTS[23] = 860; CONSTANTS[24] = 44; CONSTANTS[25] = 0.4; CONSTANTS[26] = 0.4; CONSTANTS[27] = 30; CONSTANTS[28] = 0.2e-3; CONSTANTS[29] = 0.59; CONSTANTS[30] = 0.025; CONSTANTS[31] = 0.18; CONSTANTS[32] = 9.14e-3; CONSTANTS[33] = 1.64e-3; CONSTANTS[34] = 4.375e-3; CONSTANTS[35] = 2e-4; CONSTANTS[36] = 0.9613; STATES[15] = 4.105; STATES[16] = 0.0526; STATES[17] = 0.2474; STATES[18] = 6.27339e-5; STATES[19] = 0.8374627; CONSTANTS[37] = 0.89; CONSTANTS[38] = 106; CONSTANTS[39] = 0.3; CONSTANTS[40] = 10; CONSTANTS[41] = 54; CONSTANTS[42] = 21; CONSTANTS[43] = 60; CONSTANTS[44] = 8.5; CONSTANTS[45] = 7; CONSTANTS[46] = 1; CONSTANTS[47] = 14; CONSTANTS[48] = 1; CONSTANTS[49] = 1e-3; } void computeRates(double VOI, double* CONSTANTS, double* RATES, double* STATES, double* ALGEBRAIC) { RATES[8] = CONSTANTS[10]*STATES[7] - CONSTANTS[11]*STATES[8]*STATES[6]; ALGEBRAIC[2] = ( STATES[11]*STATES[10])/CONSTANTS[26]; RATES[11] = STATES[7] - (ALGEBRAIC[2]+STATES[11]); RATES[10] = CONSTANTS[12] - (ALGEBRAIC[2]+STATES[10]); ALGEBRAIC[1] = ( STATES[12]*STATES[13])/CONSTANTS[27]; RATES[12] = CONSTANTS[14] - (ALGEBRAIC[1]+STATES[12]); RATES[13] = CONSTANTS[15] - (ALGEBRAIC[1]+STATES[13]); ALGEBRAIC[4] = ( STATES[19]*STATES[18])/CONSTANTS[49]; RATES[19] = CONSTANTS[37] - (ALGEBRAIC[4]+STATES[19]); RATES[18] = STATES[16] - (ALGEBRAIC[4]+STATES[18]); ALGEBRAIC[5] = ( STATES[5]*STATES[0]*STATES[1])/( CONSTANTS[1]*CONSTANTS[2]); ALGEBRAIC[0] = ( STATES[5]*STATES[0])/CONSTANTS[1]; RATES[5] = CONSTANTS[0] - (ALGEBRAIC[0]+ALGEBRAIC[5]+STATES[5]); RATES[3] = CONSTANTS[5]*(ALGEBRAIC[0]+ALGEBRAIC[5]) - CONSTANTS[6]*STATES[3]; ALGEBRAIC[6] = ( STATES[14]*STATES[10])/CONSTANTS[24]; RATES[14] = CONSTANTS[16] - (ALGEBRAIC[6]+STATES[14]); RATES[9] = (( CONSTANTS[17]*STATES[10]*CONSTANTS[13])/(CONSTANTS[21]+CONSTANTS[13])+( CONSTANTS[20]*ALGEBRAIC[2]*CONSTANTS[13])/(CONSTANTS[25]+CONSTANTS[13])+( CONSTANTS[18]*ALGEBRAIC[6]*CONSTANTS[13])/(CONSTANTS[23]+CONSTANTS[13])) - ( CONSTANTS[19]*STATES[12]*STATES[9])/(CONSTANTS[22]+STATES[9]); ALGEBRAIC[7] = ( STATES[0]*STATES[1])/CONSTANTS[3]; RATES[1] = CONSTANTS[4] - (ALGEBRAIC[7]+ALGEBRAIC[5]+STATES[1]); RATES[0] = STATES[2] - (ALGEBRAIC[0]+ALGEBRAIC[5]+ALGEBRAIC[7]+STATES[0]); RATES[7] = CONSTANTS[9]*(ALGEBRAIC[7]+ALGEBRAIC[5]) - CONSTANTS[10]*STATES[7]; RATES[6] = CONSTANTS[9]*(ALGEBRAIC[7]+ALGEBRAIC[5]) - CONSTANTS[11]*STATES[8]*STATES[6]; rootfind_0(VOI, CONSTANTS, RATES, STATES, ALGEBRAIC, pret); RATES[2] = ( CONSTANTS[6]*STATES[3] - CONSTANTS[5]*(ALGEBRAIC[0]+ALGEBRAIC[5]))+( CONSTANTS[8]*STATES[4] - CONSTANTS[7]*ALGEBRAIC[9]*STATES[2]); RATES[4] = CONSTANTS[7]*ALGEBRAIC[9]*STATES[2] - CONSTANTS[8]*STATES[4]; ALGEBRAIC[8] = CONSTANTS[38] - STATES[15]; RATES[15] = ( CONSTANTS[41]*ALGEBRAIC[9]*ALGEBRAIC[8])/(CONSTANTS[42]+ALGEBRAIC[8]) - ( CONSTANTS[44]*STATES[19]*STATES[15])/(CONSTANTS[45]+STATES[15]); RATES[16] = ( CONSTANTS[43]*ALGEBRAIC[9]*STATES[16])/(CONSTANTS[46]+STATES[16]) - ( CONSTANTS[47]*STATES[17])/(CONSTANTS[48]+STATES[17]); RATES[17] = ( CONSTANTS[47]*STATES[17])/(CONSTANTS[48]+STATES[17]) - ( CONSTANTS[43]*ALGEBRAIC[9]*STATES[16])/(CONSTANTS[46]+STATES[16]); } void computeVariables(double VOI, double* CONSTANTS, double* RATES, double* STATES, double* ALGEBRAIC) { ALGEBRAIC[2] = ( STATES[11]*STATES[10])/CONSTANTS[26]; ALGEBRAIC[1] = ( STATES[12]*STATES[13])/CONSTANTS[27]; ALGEBRAIC[4] = ( STATES[19]*STATES[18])/CONSTANTS[49]; ALGEBRAIC[5] = ( STATES[5]*STATES[0]*STATES[1])/( CONSTANTS[1]*CONSTANTS[2]); ALGEBRAIC[0] = ( STATES[5]*STATES[0])/CONSTANTS[1]; ALGEBRAIC[6] = ( STATES[14]*STATES[10])/CONSTANTS[24]; ALGEBRAIC[7] = ( STATES[0]*STATES[1])/CONSTANTS[3]; ALGEBRAIC[8] = CONSTANTS[38] - STATES[15]; ALGEBRAIC[3] = STATES[15]/CONSTANTS[38]; ALGEBRAIC[20] = ALGEBRAIC[8]/CONSTANTS[38]; } void objfunc_0(double *p, double *hx, int m, int n, void *adata) { struct rootfind_info* rfi = (struct rootfind_info*)adata; #define VOI rfi->aVOI #define CONSTANTS rfi->aCONSTANTS #define RATES rfi->aRATES #define STATES rfi->aSTATES #define ALGEBRAIC rfi->aALGEBRAIC #define pret rfi->aPRET ALGEBRAIC[9] = p[0]; ALGEBRAIC[10] = p[1]; ALGEBRAIC[11] = p[2]; ALGEBRAIC[12] = p[3]; ALGEBRAIC[13] = p[4]; ALGEBRAIC[14] = p[5]; ALGEBRAIC[15] = p[6]; ALGEBRAIC[16] = p[7]; ALGEBRAIC[17] = p[8]; ALGEBRAIC[18] = p[9]; ALGEBRAIC[19] = p[10]; hx[0] = ALGEBRAIC[19] - ( CONSTANTS[31]*CONSTANTS[28])/(CONSTANTS[28]+ALGEBRAIC[9]+ALGEBRAIC[11]); hx[1] = ALGEBRAIC[14] - (ALGEBRAIC[9]/CONSTANTS[34])*ALGEBRAIC[9]*(1.00000+ALGEBRAIC[19]/CONSTANTS[28]); hx[2] = ALGEBRAIC[15] - ALGEBRAIC[9]*(1.00000+ALGEBRAIC[19]/CONSTANTS[28]); hx[3] = ALGEBRAIC[16] - (ALGEBRAIC[11]/CONSTANTS[34])*ALGEBRAIC[11]*(1.00000+ALGEBRAIC[19]/CONSTANTS[28]); hx[4] = ALGEBRAIC[17] - ALGEBRAIC[11]*(1.00000+ALGEBRAIC[19]/CONSTANTS[28]); hx[5] = ALGEBRAIC[13] - (CONSTANTS[32]/ALGEBRAIC[10])*ALGEBRAIC[14]; hx[6] = ALGEBRAIC[18] - (CONSTANTS[32]/ALGEBRAIC[10])*ALGEBRAIC[16]; hx[7] = ALGEBRAIC[10] - ((STATES[9] - (ALGEBRAIC[13]+ 2.00000*ALGEBRAIC[14]+ 2.00000*ALGEBRAIC[15])) - (ALGEBRAIC[18]+ 2.00000*ALGEBRAIC[16]+ 2.00000*ALGEBRAIC[17])); hx[8] = ALGEBRAIC[12] - (( CONSTANTS[32]*CONSTANTS[33])/CONSTANTS[34]+( CONSTANTS[32]*ALGEBRAIC[10])/CONSTANTS[34]+( ALGEBRAIC[10]*ALGEBRAIC[10])/CONSTANTS[34]); hx[9] = ALGEBRAIC[9] - ( 2.00000*CONSTANTS[29]*ALGEBRAIC[10]*ALGEBRAIC[10] - ALGEBRAIC[9]*(1.00000+ALGEBRAIC[19]/CONSTANTS[28])*( ALGEBRAIC[12]*ALGEBRAIC[9]+ ALGEBRAIC[10]*ALGEBRAIC[10])); hx[10] = ALGEBRAIC[11] - ( 2.00000*CONSTANTS[30]*ALGEBRAIC[10]*ALGEBRAIC[10] - ALGEBRAIC[11]*(1.00000+ALGEBRAIC[19]/CONSTANTS[28])*( ALGEBRAIC[12]*ALGEBRAIC[11]+ ALGEBRAIC[10]*ALGEBRAIC[10])); #undef VOI #undef CONSTANTS #undef RATES #undef STATES #undef ALGEBRAIC #undef pret } void rootfind_0(double VOI, double* CONSTANTS, double* RATES, double* STATES, double* ALGEBRAIC, int* pret) { static double p[11] = {0.1,0.1,0.1,0.1,0.1,0.1,0.1,0.1,0.1,0.1,0.1}; double bp[11], work[LM_DIF_WORKSZ(11, 11)]; struct rootfind_info rfi; rfi.aVOI = VOI; rfi.aCONSTANTS = CONSTANTS; rfi.aRATES = RATES; rfi.aSTATES = STATES; rfi.aALGEBRAIC = ALGEBRAIC; rfi.aPRET = pret; do_levmar(objfunc_0, p, bp, work, pret, 11, &rfi); ALGEBRAIC[9] = p[0]; ALGEBRAIC[10] = p[1]; ALGEBRAIC[11] = p[2]; ALGEBRAIC[12] = p[3]; ALGEBRAIC[13] = p[4]; ALGEBRAIC[14] = p[5]; ALGEBRAIC[15] = p[6]; ALGEBRAIC[16] = p[7]; ALGEBRAIC[17] = p[8]; ALGEBRAIC[18] = p[9]; ALGEBRAIC[19] = p[10]; }