<DATAFILE>

[FILEINFO]
file='dips_mlx_cloexp_long.txt'
delimiter = tab
header = {time_h_, Avg_Radiance_p_s_cm_sr_, Max_Radiance, PMN_G_L_, Bact_inoc_theo, ExpSubTag, CFU_ml_lung, Cage, mouse, manipulation, Image_Number, ROI, Image_Layer, Total_Flux_p_s_, Stdev_Radiance, Min_Radiance, Death_event, Bact_inoc_real, Phage_dose_theo, Phage_dose_real, PFU_ml_lung, Monocytes_G_L_, ExpTag, Deathtime_Interval, Exp_Type, ID, doseAntiGR1, S_death, T_death1, T_death2, lCFUeq, Death, Neutro_atInf, Neutro_BefDep, Neutro_AtSacrifice, IDtemp, CFU_ml_BAL, PFU_ml_BAL, PMN_lung_cells_ml_, AM_cells_ml_, Cage_mouse, Phage_treated, CENS, lCFUeq_loq, YTYPE, Y, status, time_med, depleted, TIME, lPFU, doseClo, AMT, ADM, aGr1}

[CONTENT]
ID = {use=identifier}
CENS = {use=censored}
YTYPE = {use=observationtype}
Y = {use=observation, name={yAM_L, yB, yM_B, yN_B, yN_L, yP}, yname={'AM_L', 'B', 'M_B', 'N_B', 'N_L', 'P'}, type={continuous, continuous, continuous, continuous, continuous, continuous}}
AMT = {use=amount}
ADM = {use=administration}
TIME = {use=time}

<MODEL>

[INDIVIDUAL]
input = {AML0_pop, B_max_pop, CL50_pop, Emax_clo_pop, K_Dn_pop, K_NnB_pop, K_NnM_pop, LF_B_pop, MB0_pop, NB0_pop, NL0_pop, S_AML_pop, S_NL_pop, V_b_pop, V_l_pop, d_M_pop, eps_N_pop, ke_C_pop, kout_AM_pop, kout_MB_pop, kout_NB_pop, r_max_pop, omega_NB0, omega_eps_N, omega_NL0, omega_MB0, omega_CL50, omega_AML0, LF_P_pop, alpha_S_pop, burst_pop, decay_pop, ecl_pop, phi_pop, omega_phi, w_R_pop, psi_pop, I_k_AML_pop, K_Nm_pop, P_C_pop, omega_r_max, psi_n_pop, omega_LF_B, M_50_pop, gam_M_pop, iota_M_pop}

DEFINITION:
AML0 = {distribution=logNormal, typical=AML0_pop, sd=omega_AML0}
B_max = {distribution=logNormal, typical=B_max_pop, no-variability}
CL50 = {distribution=logNormal, typical=CL50_pop, sd=omega_CL50}
Emax_clo = {distribution=logNormal, typical=Emax_clo_pop, no-variability}
K_Dn = {distribution=logNormal, typical=K_Dn_pop, no-variability}
K_NnB = {distribution=logNormal, typical=K_NnB_pop, no-variability}
K_NnM = {distribution=logNormal, typical=K_NnM_pop, no-variability}
LF_B = {distribution=logNormal, typical=LF_B_pop, sd=omega_LF_B}
LF_P = {distribution=logNormal, typical=LF_P_pop, no-variability}
MB0 = {distribution=logNormal, typical=MB0_pop, sd=omega_MB0}
NB0 = {distribution=logNormal, typical=NB0_pop, sd=omega_NB0}
NL0 = {distribution=logNormal, typical=NL0_pop, sd=omega_NL0}
S_AML = {distribution=logNormal, typical=S_AML_pop, no-variability}
S_NL = {distribution=logNormal, typical=S_NL_pop, no-variability}
V_b = {distribution=logNormal, typical=V_b_pop, no-variability}
V_l = {distribution=logNormal, typical=V_l_pop, no-variability}
alpha_S = {distribution=logNormal, typical=alpha_S_pop, no-variability}
d_M = {distribution=logNormal, typical=d_M_pop, no-variability}
eps_N = {distribution=logNormal, typical=eps_N_pop, sd=omega_eps_N}
ke_C = {distribution=logNormal, typical=ke_C_pop, no-variability}
kout_AM = {distribution=logNormal, typical=kout_AM_pop, no-variability}
kout_MB = {distribution=logNormal, typical=kout_MB_pop, no-variability}
kout_NB = {distribution=logNormal, typical=kout_NB_pop, no-variability}
r_max = {distribution=logNormal, typical=r_max_pop, sd=omega_r_max}
burst = {distribution=logNormal, typical=burst_pop, no-variability}
decay = {distribution=logNormal, typical=decay_pop, no-variability}
ecl = {distribution=logNormal, typical=ecl_pop, no-variability}
phi = {distribution=logNormal, typical=phi_pop, sd=omega_phi}
w_R = {distribution=logNormal, typical=w_R_pop, no-variability}
psi = {distribution=logNormal, typical=psi_pop, no-variability}
I_k_AML = {distribution=logNormal, typical=I_k_AML_pop, no-variability}
K_Nm = {distribution=logNormal, typical=K_Nm_pop, no-variability}
P_C = {distribution=logNormal, typical=P_C_pop, no-variability}
psi_n = {distribution=logNormal, typical=psi_n_pop, no-variability}
M_50 = {distribution=logNormal, typical=M_50_pop, no-variability}
gam_M = {distribution=logNormal, typical=gam_M_pop, no-variability}
iota_M = {distribution=logNormal, typical=iota_M_pop, no-variability}

[LONGITUDINAL]
input = {bAM_L, aB, bM_B, bN_B, bN_L, aP}

file = 'BPNM_clo_tr_sat_rmax_newvir_noAMkill_adsinhnonlin.txt'

DEFINITION:
yAM_L = {distribution=normal, prediction=AML_BAL, errorModel=proportional(bAM_L)}
yB = {distribution=normal, prediction=log_B, errorModel=constant(aB)}
yM_B = {distribution=normal, prediction=MB, errorModel=proportional(bM_B)}
yN_B = {distribution=normal, prediction=NB, errorModel=proportional(bN_B)}
yN_L = {distribution=normal, prediction=N_BAL, errorModel=proportional(bN_L)}
yP = {distribution=normal, prediction=log_P, errorModel=constant(aP)}

<FIT>
data = {yAM_L, yB, yM_B, yN_B, yN_L, yP}
model = {yAM_L, yB, yM_B, yN_B, yN_L, yP}

<PARAMETER>
AML0_pop = {value=4000000, method=FIXED}
B_max_pop = {value=10000000000, method=FIXED}
CL50_pop = {value=0.16, method=FIXED}
Emax_clo_pop = {value=400, method=FIXED}
I_k_AML_pop = {value=0.5, method=FIXED}
K_Dn_pop = {value=5400000, method=FIXED}
K_Nm_pop = {value=100000, method=FIXED}
K_NnB_pop = {value=1400000, method=FIXED}
K_NnM_pop = {value=1000000, method=FIXED}
LF_B_pop = {value=30, method=MLE}
LF_P_pop = {value=1.54, method=FIXED}
MB0_pop = {value=400000, method=FIXED}
M_50_pop = {value=2400000, method=FIXED}
NB0_pop = {value=1500000, method=MLE}
NL0_pop = {value=81500, method=FIXED}
P_C_pop = {value=7500000, method=FIXED}
S_AML_pop = {value=0.003, method=FIXED}
S_NL_pop = {value=0.0042, method=FIXED}
V_b_pop = {value=0.0012, method=FIXED}
V_l_pop = {value=0.001, method=FIXED}
aB = {value=1, method=MLE}
aP = {value=1, method=MLE}
alpha_S_pop = {value=0.75, method=FIXED}
bAM_L = {value=0.3, method=MLE}
bM_B = {value=0.3, method=MLE}
bN_B = {value=0.3, method=MLE}
bN_L = {value=0.3, method=MLE}
burst_pop = {value=100, method=FIXED}
cAM_L = {value=1, method=FIXED}
cM_B = {value=1, method=FIXED}
cN_B = {value=1, method=FIXED}
cN_L = {value=1, method=FIXED}
d_M_pop = {value=0.6, method=FIXED}
decay_pop = {value=0.023, method=FIXED}
ecl_pop = {value=6, method=FIXED}
eps_N_pop = {value=0.00000045, method=MLE}
gam_M_pop = {value=5, method=FIXED}
iota_M_pop = {value=0.3, method=FIXED}
ke_C_pop = {value=0.14, method=FIXED}
kout_AM_pop = {value=0.001, method=FIXED}
kout_MB_pop = {value=0.04, method=FIXED}
kout_NB_pop = {value=0.115, method=FIXED}
omega_AML0 = {value=1.11, method=FIXED}
omega_CL50 = {value=0.43, method=FIXED}
omega_LF_B = {value=1, method=MLE}
omega_MB0 = {value=0.5600000000000001, method=FIXED}
omega_NB0 = {value=1, method=MLE}
omega_NL0 = {value=0.66, method=FIXED}
omega_eps_N = {value=1, method=MLE}
omega_phi = {value=1, method=MLE}
omega_r_max = {value=0.6, method=FIXED}
phi_pop = {value=0.00000005, method=MLE}
psi_n_pop = {value=0.000003, method=FIXED}
psi_pop = {value=0.0000000115, method=FIXED}
r_max_pop = {value=0.485, method=FIXED}
w_R_pop = {value=1, method=FIXED}

<MONOLIX>

[TASKS]
populationParameters()
individualParameters(method = {conditionalMean, conditionalMode })
fim(method = StochasticApproximation)
logLikelihood(method = ImportanceSampling)
plotResult(method = {indfits, parameterdistribution, covariancemodeldiagnosis, covariatemodeldiagnosis, obspred, vpc, residualsscatter, residualsdistribution, randomeffects, saemresults })

[SETTINGS]
GLOBAL:
exportpath = 'BPNM_noAMkill_adsinhnonlin_iM30_gam5'
nbchains = 3
autochains = no

POPULATION:
smoothingiterations = 500
exploratoryiterations = 1000
simulatedannealingiterations = 1000

INDIVIDUAL:
enablemaxiterations = yes

FIM:
maxiterations = 500