Debugging simulation failures

Objective: Demonstrate common simulation failures and give some hints for interpreting, debugging, and fixing them.

[1]:
%matplotlib inline
import os
from contextlib import suppress
from pathlib import Path

import matplotlib.pyplot as plt
import numpy as np
from amici import (
    SbmlImporter,
    import_model_module,
)
from amici.importers.petab.v1 import (
    import_petab_problem,
)
from amici.sim.sundials import (
    AMICI_SUCCESS,
    ExpData,
    SensitivityMethod,
    SensitivityOrder,
    SteadyStateSensitivityMode,
    run_simulation,
    simulation_status_to_str,
    unscale_parameter,
)
from amici.sim.sundials.petab.v1 import (
    EDATAS,
    RDATAS,
    simulate_petab,
)
from amici.sim.sundials.plotting import plot_jacobian, plot_state_trajectories
from petab.v1.sbml import get_sbml_model

try:
    import benchmark_models_petab
except ModuleNotFoundError:
    # install `benchmark_models_petab` if necessary
    %pip install -q -e "git+https://github.com/Benchmarking-Initiative/Benchmark-Models-PEtab.git@master#subdirectory=src/python&egg=benchmark_models_petab"
    try:
        import benchmark_models_petab
    except ModuleNotFoundError:
        print("** Please restart the kernel. **")

Overview

In the following, we will simulate models contained in the PEtab Benchmark Collection and the SBML test suite to demonstrate a number of simulation failures to analyze and fix them. We use the PEtab format, as it makes model import and simulation much easier, but everything illustrated here, also applies to plain SBML or PySB import.

Note that, due to numerical issues, the examples below may not be fully reproducible on every system.

If any simulation failures occur, they will be printed via Python logging. Additionally, they will be stored in ReturnData.messages.

Programmatically, simulation success can be checked via ReturnDataView.status. In case of a successful simulation, and only then, this value corresponds to amici.AMICI_SUCCESS. In case of a simulation error, all quantities in ReturnData/ReturnDataView will be reported up to the time of failure, the rest will be NaN. The likelihood and it’s gradient will always be NaN in case of failure.

AMICI_TOO_MUCH_WORK - mxstep steps taken before reaching tout

Let’s run a simulation:

[2]:
petab_problem = benchmark_models_petab.get_problem("Fujita_SciSignal2010")
amici_model = import_petab_problem(petab_problem, verbose=False, compile_=None)

np.random.seed(2991)
problem_parameters = dict(
    zip(
        petab_problem.x_free_ids,
        petab_problem.sample_parameter_startpoints(n_starts=1)[0],
    )
)
res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
)
print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)
assert [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]] == [
    "AMICI_SUCCESS",
    "AMICI_SUCCESS",
    "AMICI_SUCCESS",
    "AMICI_TOO_MUCH_WORK",
    "AMICI_NOT_RUN",
    "AMICI_NOT_RUN",
]
2026-06-29 07:08:16.310 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.311 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.313 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.313 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.314 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:16.315 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:16.316 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.317 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.318 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.319 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.320 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:16.320 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:16.321 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.322 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.323 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.323 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.324 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:16.326 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:16.326 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.327 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.327 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.328 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.328 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.329 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.329 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.330 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.330 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.331 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.331 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.332 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.332 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.334 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.334 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.335 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.335 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
2026-06-29 07:08:16.336 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
2026-06-29 07:08:16.444 - amici.sim.sundials._swig_wrappers - DEBUG - [condition_step_03_0][cvodes:CVode:TOO_MUCH_WORK] At t = 3031.8, mxstep steps taken before reaching tout.
2026-06-29 07:08:16.445 - amici.sim.sundials._swig_wrappers - ERROR - [condition_step_03_0][FORWARD_FAILURE] AMICI forward simulation failed at t = 3031.8: AMICI failed to integrate the forward problem
Status: ['AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_TOO_MUCH_WORK', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN']

What happened?

AMICI failed to integrate the forward problem. The problem occurred for only one simulation condition, condition_step_03_0. The issue occurred at \(t = 3031.8\), where the CVODES reached the maximum number of steps.

How to address?

The number of steps the solver has to take is closely related to the chosen error tolerance. More accurate results, more steps. Therefore, this problem can be solved in two ways:

  1. Increasing the maximum number of steps via Solver.set_max_steps. Note that this will increase the time required for simulation, and that simulation may still fail eventually. Sometimes it may be preferable to not increase this limit but rather fail fast. Also note that increasing the number of allowed steps increase RAM requirements (even if fewer steps are actually taken), so don’t set this to ridiculously large values in order to avoid this error.

  2. Reducing the number of steps CVODES has to take. This is determined by the required error tolerance. There are various solver error tolerances than can be adjusted. The most relevant ones are those controlled via Solver.set_relative_tolerance() and Solver.set_absolute_tolerance().

So, let’s fix that:

[3]:
# let's increase the allowed number of steps by 10x:
print("Increasing allowed number of steps ...")
amici_solver = amici_model.create_solver()
amici_solver.set_max_steps(10 * amici_solver.get_max_steps())

res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
    solver=amici_solver,
)

print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)
assert all(rdata.status == AMICI_SUCCESS for rdata in res[RDATAS])
print("Simulations finished successfully.")
print()


# let's relax the relative error tolerance by a factor of 50
print("Relaxing relative error tolerance ...")
amici_solver = amici_model.create_solver()
amici_solver.set_relative_tolerance(50 * amici_solver.get_relative_tolerance())

res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
    solver=amici_solver,
)
print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)
assert all(rdata.status == AMICI_SUCCESS for rdata in res[RDATAS])
print("Simulations finished successfully.")
2026-06-29 07:08:16.509 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.510 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.510 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.512 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.512 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:16.512 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:16.513 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.514 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.514 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.515 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.515 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:16.516 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:16.517 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.517 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.518 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.518 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.519 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:16.519 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:16.520 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.521 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.521 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.522 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.522 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.523 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.523 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.524 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.524 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.525 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.525 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.526 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.526 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.527 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.527 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.528 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.528 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
2026-06-29 07:08:16.529 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
Increasing allowed number of steps ...
2026-06-29 07:08:16.726 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.726 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.728 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.728 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.729 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:16.730 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:16.731 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.732 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.733 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.734 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.735 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:16.735 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:16.736 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.737 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.737 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.738 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.738 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:16.739 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:16.739 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.740 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.740 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.741 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.741 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.742 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.742 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.743 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.743 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.744 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.744 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.745 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:16.745 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:16.746 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:16.746 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:16.747 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:16.747 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
2026-06-29 07:08:16.748 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
Status: ['AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS']
Simulations finished successfully.

Relaxing relative error tolerance ...
Status: ['AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS']
Simulations finished successfully.

Internal t = [...] and h = [...] are such that t + h = t on the next step

Let’s run a simulation:

[4]:
petab_problem = benchmark_models_petab.get_problem("Crauste_CellSystems2017")
amici_model = import_petab_problem(petab_problem, verbose=False)

np.random.seed(1)
problem_parameters = dict(
    zip(
        petab_problem.x_free_ids,
        petab_problem.sample_parameter_startpoints(n_starts=1)[0],
    )
)
res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
)
print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)
assert [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]] == [
    "AMICI_TOO_MUCH_WORK"
]
2026-06-29 07:08:32.362 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'delta_EL': 'delta_EL', 'delta_LM': 'delta_LM', 'delta_NE': 'delta_NE', 'mu_EE': 'mu_EE', 'mu_LE': 'mu_LE', 'mu_LL': 'mu_LL', 'mu_N': 'mu_N', 'mu_P': 'mu_P', 'mu_PE': 'mu_PE', 'mu_PL': 'mu_PL', 'rho_E': 'rho_E', 'rho_P': 'rho_P', 'noiseParameter1_observable_EarlyEffector': 1540, 'noiseParameter1_observable_LateEffector': 2705, 'noiseParameter1_observable_Memory': 7909, 'noiseParameter1_observable_Naive': 64}, {}, {'delta_EL': 'log10', 'delta_LM': 'log10', 'delta_NE': 'log10', 'mu_EE': 'log10', 'mu_LE': 'log10', 'mu_LL': 'log10', 'mu_N': 'log10', 'mu_P': 'log10', 'mu_PE': 'log10', 'mu_PL': 'log10', 'rho_E': 'log10', 'rho_P': 'log10', 'noiseParameter1_observable_EarlyEffector': 'lin', 'noiseParameter1_observable_LateEffector': 'lin', 'noiseParameter1_observable_Memory': 'lin', 'noiseParameter1_observable_Naive': 'lin'})
2026-06-29 07:08:32.363 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:32.364 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {}
2026-06-29 07:08:32.365 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:32.365 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'delta_EL': 'delta_EL', 'delta_LM': 'delta_LM', 'delta_NE': 'delta_NE', 'mu_EE': 'mu_EE', 'mu_LE': 'mu_LE', 'mu_LL': 'mu_LL', 'mu_N': 'mu_N', 'mu_P': 'mu_P', 'mu_PE': 'mu_PE', 'mu_PL': 'mu_PL', 'rho_E': 'rho_E', 'rho_P': 'rho_P', 'noiseParameter1_observable_EarlyEffector': 1540, 'noiseParameter1_observable_LateEffector': 2705, 'noiseParameter1_observable_Memory': 7909, 'noiseParameter1_observable_Naive': 64}
2026-06-29 07:08:32.367 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'delta_EL': 'delta_EL', 'delta_LM': 'delta_LM', 'delta_NE': 'delta_NE', 'mu_EE': 'mu_EE', 'mu_LE': 'mu_LE', 'mu_LL': 'mu_LL', 'mu_N': 'mu_N', 'mu_P': 'mu_P', 'mu_PE': 'mu_PE', 'mu_PL': 'mu_PL', 'rho_E': 'rho_E', 'rho_P': 'rho_P', 'noiseParameter1_observable_EarlyEffector': 1540, 'noiseParameter1_observable_LateEffector': 2705, 'noiseParameter1_observable_Memory': 7909, 'noiseParameter1_observable_Naive': 64}
2026-06-29 07:08:32.393 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.394 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.395 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.396 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.397 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.398 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.399 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.400 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.400 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.401 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] Internal t = 0.330112 and h = 2.06577e-17 are such that t + h = t on the next step. The solver will continue anyway.
2026-06-29 07:08:32.401 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:WARNING] The above warning has been issued mxhnil times and will not be issued again for this problem.
2026-06-29 07:08:32.402 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:TOO_MUCH_WORK] At t = 0.330112, mxstep steps taken before reaching tout.
2026-06-29 07:08:32.402 - amici.sim.sundials._swig_wrappers - ERROR - [model1_data1][FORWARD_FAILURE] AMICI forward simulation failed at t = 0.330112: AMICI failed to integrate the forward problem
Status: ['AMICI_TOO_MUCH_WORK']

What happened?

The forward simulation failed because the AMICI solver exceeded the maximum number of steps. Unlike in the previous case of mxstep steps taken before reaching tout (see above), here we got several additional warnings that the current step size \(h\) is numerically zero.

How to address?

The warning Internal t = [...] and h = [...] are such that t + h = t on the next step tells us that the solver is not able to move forward. The solver may be able to recover from that, but not always.

Let’s look at the state trajectories to see what’s going on. Such a tiny step size is usually related to very fast dynamics. We repeat the simulation with additional timepoints before the point of failure:

[5]:
# Create a copy of this simulation condition
edata = ExpData(res[EDATAS][0])
edata.set_timepoints(np.linspace(0, 0.33011, 5000))
amici_solver = amici_model.create_solver()
rdata = run_simulation(amici_model, amici_solver, edata)

# Visualize state trajectories
plot_state_trajectories(rdata)
plt.yscale("log")
../_images/examples_example_errors_10_0.svg

We can see a steep increase for Pathogen just before the error occurs. Let’s zoom in:

[6]:
plt.plot(rdata.t, rdata.by_id("Pathogen"))
plt.xlabel("time")
plt.ylabel("Pathogen");
../_images/examples_example_errors_12_0.svg

The solver is unable to handle such a steep increase. There is not much we can do. Increasing the tolerances will let the solver proceed a bit further, but this is usually not enough. Most likely there is a problem in the model or in the choice of parameter values.

the error test failed repeatedly or with |h| = hmin

Let’s run a simulation:

[7]:
petab_problem = benchmark_models_petab.get_problem("Fujita_SciSignal2010")
amici_model = import_petab_problem(petab_problem, verbose=False)

np.random.seed(4920)
problem_parameters = dict(
    zip(
        petab_problem.x_free_ids,
        petab_problem.sample_parameter_startpoints(n_starts=1)[0],
    )
)
res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
)
print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)

assert [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]] == [
    "AMICI_SUCCESS",
    "AMICI_ERR_FAILURE",
    "AMICI_NOT_RUN",
    "AMICI_NOT_RUN",
    "AMICI_NOT_RUN",
    "AMICI_NOT_RUN",
]
2026-06-29 07:08:33.707 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:33.707 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:33.709 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:33.710 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:33.711 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:33.712 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:33.713 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:33.713 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:33.714 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:33.715 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:33.716 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:33.717 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:33.718 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:33.719 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:33.720 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:33.722 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:33.722 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:33.724 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:33.724 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:33.725 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:33.726 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:33.727 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:33.727 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:33.728 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:33.728 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:33.729 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:33.730 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:33.730 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:33.731 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:33.731 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:33.733 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:33.734 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:33.734 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:33.735 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:33.735 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
2026-06-29 07:08:33.735 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
2026-06-29 07:08:33.828 - amici.sim.sundials._swig_wrappers - DEBUG - [condition_step_00_3][cvodes:cvHandleFailure:ERR_FAILURE] At t = 429.232 and h = 7.75194e-05, the error test failed repeatedly or with |h| = hmin.
2026-06-29 07:08:33.829 - amici.sim.sundials._swig_wrappers - ERROR - [condition_step_00_3][FORWARD_FAILURE] AMICI forward simulation failed at t = 429.232: AMICI failed to integrate the forward problem
Status: ['AMICI_SUCCESS', 'AMICI_ERR_FAILURE', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN']

What happened?

AMICI failed to integrate the forward problem. The problem occurred for only one simulation condition, condition_step_00_3. The issue occurred at \(t = 429.232\), where the error test failed. This means, the solver is unable to take a step of non-zero size without violating the chosen error tolerances.

How to address?

The step size is computed based on the Jacobian. Inspecting ReturnData.J shows us that we have rather large values in the Jacobian:

[8]:
rdata = res[RDATAS][1]

# Show Jacobian as heatmap
plot_jacobian(rdata)

print(f"largest absolute Jacobian value: {np.max(np.abs(rdata.J)):.3g}")
largest absolute Jacobian value: 4.09e+05
../_images/examples_example_errors_18_1.svg

In this case, the default relative error tolerance may be too high and lead too large absolute errors.

Let’s retry simulation using stricter tolerances:

[9]:
# set stricter relative error tolerance
amici_solver = amici_model.create_solver()
amici_solver.set_relative_tolerance(amici_solver.get_relative_tolerance() / 10)

res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
    solver=amici_solver,
)
print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)
assert all(rdata.status == AMICI_SUCCESS for rdata in res[RDATAS])
print("Simulations finished successfully.")
2026-06-29 07:08:34.267 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:34.268 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:34.268 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.1, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:34.269 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:34.270 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:34.270 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.035}
2026-06-29 07:08:34.271 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:34.272 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:34.272 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 0.3, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:34.273 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:34.273 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:34.274 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.025}
2026-06-29 07:08:34.275 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:34.276 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:34.276 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 1.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:34.277 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:34.278 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:34.278 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.075}
2026-06-29 07:08:34.279 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:34.280 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:34.280 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 3.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:34.281 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:34.283 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:34.283 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.02, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:34.284 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:34.285 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:34.285 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 10.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:34.286 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:34.287 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:34.287 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.08}
2026-06-29 07:08:34.288 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0, 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}, {}, {'EGFR_turnover': 'log10', 'init_AKT': 'log10', 'init_EGFR': 'log10', 'init_S6': 'log10', 'reaction_1_k1': 'log10', 'reaction_1_k2': 'log10', 'reaction_2_k1': 'log10', 'reaction_2_k2': 'log10', 'reaction_3_k1': 'log10', 'reaction_4_k1': 'log10', 'reaction_5_k1': 'log10', 'reaction_5_k2': 'log10', 'reaction_6_k1': 'log10', 'reaction_7_k1': 'log10', 'reaction_8_k1': 'log10', 'reaction_9_k1': 'log10', 'EGF_0': 'lin', 'EGF_rate': 'lin', 'EGF_end': 'lin', 'observableParameter1_pAkt_tot': 'log10', 'observableParameter1_pEGFR_tot': 'log10', 'observableParameter1_pS6_tot': 'log10', 'noiseParameter1_pAkt_tot': 'lin', 'noiseParameter1_pEGFR_tot': 'lin', 'noiseParameter1_pS6_tot': 'lin'})
2026-06-29 07:08:34.288 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:08:34.289 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'EGF_0': 30.0, 'EGF_rate': 0.0, 'EGF_end': 3600.0}
2026-06-29 07:08:34.289 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:08:34.290 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
2026-06-29 07:08:34.290 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'EGFR_turnover': 'EGFR_turnover', 'init_AKT': 'init_AKT', 'init_EGFR': 'init_EGFR', 'init_S6': 'init_S6', 'reaction_1_k1': 'reaction_1_k1', 'reaction_1_k2': 'reaction_1_k2', 'reaction_2_k1': 'reaction_2_k1', 'reaction_2_k2': 'reaction_2_k2', 'reaction_3_k1': 'reaction_3_k1', 'reaction_4_k1': 'reaction_4_k1', 'reaction_5_k1': 'reaction_5_k1', 'reaction_5_k2': 'reaction_5_k2', 'reaction_6_k1': 'reaction_6_k1', 'reaction_7_k1': 'reaction_7_k1', 'reaction_8_k1': 'reaction_8_k1', 'reaction_9_k1': 'reaction_9_k1', 'observableParameter1_pAkt_tot': 'scaling_pAkt_tot', 'observableParameter1_pEGFR_tot': 'scaling_pEGFR_tot', 'observableParameter1_pS6_tot': 'scaling_pS6_tot', 'noiseParameter1_pAkt_tot': 0.01, 'noiseParameter1_pEGFR_tot': 0.01, 'noiseParameter1_pS6_tot': 0.07}
Status: ['AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS']
Simulations finished successfully.

Cvode routine CVode returned a root after reinitialization

Let’s run a simulation:

[ ]:

[10]:
# retrieve and import the SBML model
if "imported_00885" not in globals():
    sbml_reader, sbml_document, sbml_model = get_sbml_model(
        "https://raw.githubusercontent.com/sbmlteam/sbml-test-suite/7ab011efe471877987b5d6dcba8cc19a6ff71254/cases/semantic/00885/00885-sbml-l3v2.xml"
    )
    SbmlImporter(sbml_model).sbml2amici(
        model_name="sbml_00885", output_dir="amici_models/sbml_00885"
    )
    imported_00885 = True

amici_model = import_model_module(
    "sbml_00885", "amici_models/sbml_00885"
).get_model()

# run the simulation
amici_solver = amici_model.create_solver()
amici_solver.set_sensitivity_method(SensitivityMethod.forward)
amici_solver.set_sensitivity_order(SensitivityOrder.first)
amici_model.set_timepoints(np.linspace(0, 6, 51))
rdata = run_simulation(amici_model, amici_solver)
print("Status:", simulation_status_to_str(rdata.status))
assert simulation_status_to_str(rdata.status) == "AMICI_ERROR"
2026-06-29 07:08:51.569 - amici.sim.sundials._swig_wrappers - ERROR - [OTHER] AMICI simulation failed: CVODE routine CVode returned a root after reinitialization at t=2.107007. The initial step-size after the event or Heaviside function is too small. To fix this, adjust absolute or relative tolerances! failed with error code 2.
Status: AMICI_ERROR

What happened?

The simulation failed because the initial step-size after an event or Heaviside function was too small. The error occurred around t=2.1.

How to address?

The error message already suggests a fix for this situation, so let’s try decreasing the relative tolerance:

[11]:
amici_solver = amici_model.create_solver()
amici_solver.set_sensitivity_method(SensitivityMethod.forward)
amici_solver.set_sensitivity_order(SensitivityOrder.first)
amici_solver.set_relative_tolerance(1e-15)
amici_model.set_timepoints(np.linspace(0, 6, 51))
rdata = run_simulation(amici_model, amici_solver)
print("Status:", simulation_status_to_str(rdata.status))
assert simulation_status_to_str(rdata.status) == "AMICI_SUCCESS"
Status: AMICI_SUCCESS

Sometimes this problem can also be solved be increasing tolerances or by slightly changing the output timepoints.

AMICI encountered a NaN / Inf value for [...]

Let’s run a simulation:

[12]:
petab_problem = benchmark_models_petab.get_problem("Borghans_BiophysChem1997")
amici_model = import_petab_problem(petab_problem, verbose=False)

np.random.seed(18)
problem_parameters = dict(
    zip(
        petab_problem.x_free_ids,
        petab_problem.sample_parameter_startpoints(n_starts=1)[0],
    )
)
res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
)
print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)
assert [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]] == [
    "AMICI_FIRST_RHSFUNC_ERR"
]
2026-06-29 07:09:07.772 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'K2': 'K2', 'K_par': 'K_par', 'Ka': 'Ka', 'Kd': 'Kd', 'Kf': 'Kf', 'Kp': 'Kp', 'Ky': 'Ky', 'Kz': 'Kz', 'Vd': 'Vd', 'Vm2': 'Vm2', 'Vm3': 'Vm3', 'Vp': 'Vp', 'beta_par': 'beta_par', 'epsilon_par': 'epsilon_par', 'init_A_state': 'init_A_state', 'init_Y_state': 'init_Y_state', 'init_Z_state': 'init_Z_state', 'n_par': 'n_par', 'v0': 'v0', 'v1': 'v1', 'observableParameter1_Ca': 'offset', 'observableParameter2_Ca': 'scale', 'noiseParameter1_Ca': 'sigma'}, {}, {'K2': 'log10', 'K_par': 'log10', 'Ka': 'log10', 'Kd': 'log10', 'Kf': 'log10', 'Kp': 'log10', 'Ky': 'log10', 'Kz': 'log10', 'Vd': 'log10', 'Vm2': 'log10', 'Vm3': 'log10', 'Vp': 'log10', 'beta_par': 'log10', 'epsilon_par': 'log10', 'init_A_state': 'lin', 'init_Y_state': 'lin', 'init_Z_state': 'lin', 'n_par': 'log10', 'v0': 'log10', 'v1': 'log10', 'observableParameter1_Ca': 'log10', 'observableParameter2_Ca': 'log10', 'noiseParameter1_Ca': 'log10'})
2026-06-29 07:09:07.773 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:09:07.773 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {}
2026-06-29 07:09:07.774 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:09:07.775 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'K2': 'K2', 'K_par': 'K_par', 'Ka': 'Ka', 'Kd': 'Kd', 'Kf': 'Kf', 'Kp': 'Kp', 'Ky': 'Ky', 'Kz': 'Kz', 'Vd': 'Vd', 'Vm2': 'Vm2', 'Vm3': 'Vm3', 'Vp': 'Vp', 'beta_par': 'beta_par', 'epsilon_par': 'epsilon_par', 'init_A_state': 'init_A_state', 'init_Y_state': 'init_Y_state', 'init_Z_state': 'init_Z_state', 'n_par': 'n_par', 'v0': 'v0', 'v1': 'v1', 'observableParameter1_Ca': 'offset', 'observableParameter2_Ca': 'scale', 'noiseParameter1_Ca': 'sigma'}
2026-06-29 07:09:07.775 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'K2': 'K2', 'K_par': 'K_par', 'Ka': 'Ka', 'Kd': 'Kd', 'Kf': 'Kf', 'Kp': 'Kp', 'Ky': 'Ky', 'Kz': 'Kz', 'Vd': 'Vd', 'Vm2': 'Vm2', 'Vm3': 'Vm3', 'Vp': 'Vp', 'beta_par': 'beta_par', 'epsilon_par': 'epsilon_par', 'init_A_state': 'init_A_state', 'init_Y_state': 'init_Y_state', 'init_Z_state': 'init_Z_state', 'n_par': 'n_par', 'v0': 'v0', 'v1': 'v1', 'observableParameter1_Ca': 'offset', 'observableParameter2_Ca': 'scale', 'noiseParameter1_Ca': 'sigma'}
2026-06-29 07:09:07.940 - amici.sim.sundials._swig_wrappers - WARNING - [model1_data1][AMICI:NaN] AMICI encountered a NaN value for xdot[2] (A_state) at t=0.000000
2026-06-29 07:09:07.941 - amici.sim.sundials._swig_wrappers - WARNING - [model1_data1][AMICI:NaN] AMICI encountered a NaN value for w[6] (flux_v7_v_6) at t=0.000000
2026-06-29 07:09:07.942 - amici.sim.sundials._swig_wrappers - DEBUG - [model1_data1][cvodes:CVode:FIRST_RHSFUNC_ERR] The right-hand side routine failed at the first call.
2026-06-29 07:09:07.943 - amici.sim.sundials._swig_wrappers - ERROR - [model1_data1][FORWARD_FAILURE] AMICI forward simulation failed at t = 0: AMICI failed to integrate the forward problem
Status: ['AMICI_FIRST_RHSFUNC_ERR']

What happened?

The forward simulation failed because AMICI encountered a NaN value when simulating condition model1_data1. Then NaNs occurred in \(\dot x\) and \(w\) (model expressions, such as reaction fluxes or assignment rules). Furthermore, the failure occurred at the first call, so at \(t = t_0\) (here: \(t = 0\)).

How to address?

The NaN in \(\dot x\) is most likely a consequence of the one in \(w\). (A subset of) the dependency tree looks something like:

image1

Always look for the most basic (furthest up) model quantities. In cases where non-finite values occur in expressions further down, rerunning the simulation after calling Model.setAlwaysCheckFinite(True) may give some further hints on where the issue originates.

The NaN in \(w\) occurred for flux_v7_v_6 (see error log), i.e., when computing the reaction flux for reaction v7_v_6. As \(w\) only depends on \((t, p, k, x)\) and no non-finite values have been reported for those, the issue has to be in the respective flux equation.

Let’s look at that expression. This can either be done by inspecting the underlying SBML model (e.g., using COPASI), or by checking the generated model code:

[13]:
# model source code location
model_src_dir = Path(amici_model.module.__file__).parents[1]

# find the problematic expression in the model source code
!grep flux_v7_v_6 {model_src_dir}/w.cpp
    flux_v7_v_6 = std::pow(A_state, 2)*Vd*std::pow(Z_state, n_par)/((std::pow(A_state, 2) + std::pow(Kp, 2))*(std::pow(Kd, n_par) + std::pow(Z_state, n_par)));  // w[6]

What could go wrong? We can obtain NaN from any of these symbols being NaN, or through division by zero.

Let’s let’s check the denominator first:

\[(A\_state^2 + Kp^2)*(Kd^{n\_par} + Z\_state^{n\_par})\]

A_state and Z_state are state variables, Kd, K_p, and n_par are parameters.

As the error occurred at \(t = t_0\), let’s ensure the initial state is non-zero and finite:

[14]:
rdata = res[RDATAS][0]
edata = res[EDATAS][0]
# check initial states
x0 = dict(zip(amici_model.get_state_ids(), rdata.x0))
print(f"{x0=}")
x0={'Z_state': np.float64(0.6869701913398437), 'Y_state': np.float64(0.2977237418558598), 'A_state': np.float64(0.1116031306650328)}

The initial states are fine - the first multiplicand is non-zero, as \(x_0\) was non-zero.

So let’s check the parameter values occurring in the second multiplicand:

[15]:
# we have to account for the chosen parameter scale
from itertools import starmap

unscaled_parameter = dict(
    zip(
        amici_model.get_free_parameter_ids(),
        starmap(unscale_parameter, zip(edata.free_parameters, edata.pscale)),
    )
)
print(dict((p, unscaled_parameter[p]) for p in ("Kd", "Kp", "n_par")))
{'Kd': 0.028491925689008366, 'Kp': 1002.513636749445, 'n_par': 7816.430091706722}

Considering that n_par occurs as exponent, it’s magnitude looks pretty high. This term is very likely causing the problem - let’s check:

[16]:
print(
    f"{x0['Z_state']**unscaled_parameter['n_par'] + unscaled_parameter['Kd']**unscaled_parameter['n_par']=}"
)
x0['Z_state']**unscaled_parameter['n_par'] + unscaled_parameter['Kd']**unscaled_parameter['n_par']=np.float64(0.0)

Indeed, no way we can fix this for the given model. This was most likely an unrealistic parameter value, originating from a too high upper parameter bound for n_par. Therefore, if this error occurs during optimization, a first step could be adapting the respective parameter bounds. In other cases, this may be a result of unfortunate arrangement of model expressions, which can sometimes be solved by passing a suitable simplification function to the model import.

Steady state sensitivity computation failed due to unsuccessful factorization of RHS Jacobian

Let’s run a simulation:

[17]:
petab_problem = benchmark_models_petab.get_problem("Blasi_CellSystems2016")
with suppress(KeyError):
    del os.environ["AMICI_EXPERIMENTAL_SBML_NONCONST_CLS"]
amici_model = import_petab_problem(
    petab_problem,
    verbose=False,
    compile_=True,
    model_name="Blasi_CellSystems2016_1",
)

amici_solver = amici_model.create_solver()
amici_solver.set_sensitivity_method(SensitivityMethod.forward)
amici_solver.set_sensitivity_order(SensitivityOrder.first)
amici_model.set_steady_state_sensitivity_mode(
    SteadyStateSensitivityMode.newtonOnly
)

np.random.seed(2020)
problem_parameters = dict(
    zip(
        petab_problem.x_free_ids,
        petab_problem.sample_parameter_startpoints(n_starts=1)[0],
    )
)
res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
    solver=amici_solver,
)
print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)

# hard to reproduce on GHA
if os.getenv("GITHUB_ACTIONS") is None:
    assert [
        simulation_status_to_str(rdata.status) for rdata in res[RDATAS]
    ] == ["AMICI_ERROR"]
2026-06-29 07:09:25.422 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'d': np.float64(0.0), 'a_k8': 'a_k8', 'a_k5_k5k12': 'a_k5_k5k12', 'a_k12_k5k12': 'a_k12_k5k12', 'a_k16_k12k16': 'a_k16_k12k16', 'a_k5k12_k5k8k12': 'a_k5k12_k5k8k12', 'a_k12k16_k8k12k16': 'a_k12k16_k8k12k16', 'a_k8k12k16_4ac': 'a_k8k12k16_4ac', 'a_basal': 'a_basal', 'noiseParameter1_observable_0ac': 'sigma', 'noiseParameter1_observable_4ac': 'sigma', 'noiseParameter1_observable_k12': 'sigma', 'noiseParameter1_observable_k12k16': 'sigma', 'noiseParameter1_observable_k16': 'sigma', 'noiseParameter1_observable_k5': 'sigma', 'noiseParameter1_observable_k5k12': 'sigma', 'noiseParameter1_observable_k5k12k16': 'sigma', 'noiseParameter1_observable_k5k16': nan, 'noiseParameter1_observable_k5k8': 'sigma', 'noiseParameter1_observable_k5k8k12': 'sigma', 'noiseParameter1_observable_k5k8k16': 'sigma', 'noiseParameter1_observable_k8': 'sigma', 'noiseParameter1_observable_k8k12': 'sigma', 'noiseParameter1_observable_k8k12k16': 'sigma', 'noiseParameter1_observable_k8k16': 'sigma'}, {}, {'d': 'log10', 'a_k8': 'log10', 'a_k5_k5k12': 'log10', 'a_k12_k5k12': 'log10', 'a_k16_k12k16': 'log10', 'a_k5k12_k5k8k12': 'log10', 'a_k12k16_k8k12k16': 'log10', 'a_k8k12k16_4ac': 'log10', 'a_basal': 'log10', 'noiseParameter1_observable_0ac': 'log10', 'noiseParameter1_observable_4ac': 'log10', 'noiseParameter1_observable_k12': 'log10', 'noiseParameter1_observable_k12k16': 'log10', 'noiseParameter1_observable_k16': 'log10', 'noiseParameter1_observable_k5': 'log10', 'noiseParameter1_observable_k5k12': 'log10', 'noiseParameter1_observable_k5k12k16': 'log10', 'noiseParameter1_observable_k5k16': 'lin', 'noiseParameter1_observable_k5k8': 'log10', 'noiseParameter1_observable_k5k8k12': 'log10', 'noiseParameter1_observable_k5k8k16': 'log10', 'noiseParameter1_observable_k8': 'log10', 'noiseParameter1_observable_k8k12': 'log10', 'noiseParameter1_observable_k8k12k16': 'log10', 'noiseParameter1_observable_k8k16': 'log10'})
2026-06-29 07:09:25.424 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:09:25.424 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'d': np.float64(0.0)}
2026-06-29 07:09:25.425 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:09:25.426 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'a_k8': 'a_k8', 'a_k5_k5k12': 'a_k5_k5k12', 'a_k12_k5k12': 'a_k12_k5k12', 'a_k16_k12k16': 'a_k16_k12k16', 'a_k5k12_k5k8k12': 'a_k5k12_k5k8k12', 'a_k12k16_k8k12k16': 'a_k12k16_k8k12k16', 'a_k8k12k16_4ac': 'a_k8k12k16_4ac', 'a_basal': 'a_basal', 'noiseParameter1_observable_0ac': 'sigma', 'noiseParameter1_observable_4ac': 'sigma', 'noiseParameter1_observable_k12': 'sigma', 'noiseParameter1_observable_k12k16': 'sigma', 'noiseParameter1_observable_k16': 'sigma', 'noiseParameter1_observable_k5': 'sigma', 'noiseParameter1_observable_k5k12': 'sigma', 'noiseParameter1_observable_k5k12k16': 'sigma', 'noiseParameter1_observable_k5k16': nan, 'noiseParameter1_observable_k5k8': 'sigma', 'noiseParameter1_observable_k5k8k12': 'sigma', 'noiseParameter1_observable_k5k8k16': 'sigma', 'noiseParameter1_observable_k8': 'sigma', 'noiseParameter1_observable_k8k12': 'sigma', 'noiseParameter1_observable_k8k12k16': 'sigma', 'noiseParameter1_observable_k8k16': 'sigma'}
2026-06-29 07:09:25.427 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'a_k8': 'a_k8', 'a_k5_k5k12': 'a_k5_k5k12', 'a_k12_k5k12': 'a_k12_k5k12', 'a_k16_k12k16': 'a_k16_k12k16', 'a_k5k12_k5k8k12': 'a_k5k12_k5k8k12', 'a_k12k16_k8k12k16': 'a_k12k16_k8k12k16', 'a_k8k12k16_4ac': 'a_k8k12k16_4ac', 'a_basal': 'a_basal', 'noiseParameter1_observable_0ac': 'sigma', 'noiseParameter1_observable_4ac': 'sigma', 'noiseParameter1_observable_k12': 'sigma', 'noiseParameter1_observable_k12k16': 'sigma', 'noiseParameter1_observable_k16': 'sigma', 'noiseParameter1_observable_k5': 'sigma', 'noiseParameter1_observable_k5k12': 'sigma', 'noiseParameter1_observable_k5k12k16': 'sigma', 'noiseParameter1_observable_k5k16': nan, 'noiseParameter1_observable_k5k8': 'sigma', 'noiseParameter1_observable_k5k8k12': 'sigma', 'noiseParameter1_observable_k5k8k16': 'sigma', 'noiseParameter1_observable_k8': 'sigma', 'noiseParameter1_observable_k8k12': 'sigma', 'noiseParameter1_observable_k8k12k16': 'sigma', 'noiseParameter1_observable_k8k16': 'sigma'}
2026-06-29 07:09:25.450 - amici.sim.sundials._swig_wrappers - ERROR - [control][OTHER] AMICI simulation failed: Steady state sensitivity computation failed due to unsuccessful factorization of RHS Jacobian
Status: ['AMICI_ERROR']

What happened?

AMICI failed to compute steady-state sensitivities, because it was not able to factorize the Jacobian.

How to address?

This is most likely a result of a singular Jacobian. Let’s check the condition number:

[18]:
rdata = res[RDATAS][0]
np.linalg.cond(rdata.J)
[18]:
np.float64(1.7144291755459935e+18)

Indeed, the condition number shows that the Jacobian is numerically singular. If this happens consistently, it is usually due to conserved quantities in the model.

There are two ways we can address that:

  1. Use numerical integration to compute sensitivities, for which a singular Jacobian is not an issue. This is, usually, slower, though.

  2. Remove any conserved quantities.

Let’s try both approaches:

[19]:
# use numerical integration
amici_model.set_steady_state_sensitivity_mode(
    SteadyStateSensitivityMode.integrationOnly
)

res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
    solver=amici_solver,
)
print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)
assert all(rdata.status == AMICI_SUCCESS for rdata in res[RDATAS])
2026-06-29 07:09:25.508 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'d': np.float64(0.0), 'a_k8': 'a_k8', 'a_k5_k5k12': 'a_k5_k5k12', 'a_k12_k5k12': 'a_k12_k5k12', 'a_k16_k12k16': 'a_k16_k12k16', 'a_k5k12_k5k8k12': 'a_k5k12_k5k8k12', 'a_k12k16_k8k12k16': 'a_k12k16_k8k12k16', 'a_k8k12k16_4ac': 'a_k8k12k16_4ac', 'a_basal': 'a_basal', 'noiseParameter1_observable_0ac': 'sigma', 'noiseParameter1_observable_4ac': 'sigma', 'noiseParameter1_observable_k12': 'sigma', 'noiseParameter1_observable_k12k16': 'sigma', 'noiseParameter1_observable_k16': 'sigma', 'noiseParameter1_observable_k5': 'sigma', 'noiseParameter1_observable_k5k12': 'sigma', 'noiseParameter1_observable_k5k12k16': 'sigma', 'noiseParameter1_observable_k5k16': nan, 'noiseParameter1_observable_k5k8': 'sigma', 'noiseParameter1_observable_k5k8k12': 'sigma', 'noiseParameter1_observable_k5k8k16': 'sigma', 'noiseParameter1_observable_k8': 'sigma', 'noiseParameter1_observable_k8k12': 'sigma', 'noiseParameter1_observable_k8k12k16': 'sigma', 'noiseParameter1_observable_k8k16': 'sigma'}, {}, {'d': 'log10', 'a_k8': 'log10', 'a_k5_k5k12': 'log10', 'a_k12_k5k12': 'log10', 'a_k16_k12k16': 'log10', 'a_k5k12_k5k8k12': 'log10', 'a_k12k16_k8k12k16': 'log10', 'a_k8k12k16_4ac': 'log10', 'a_basal': 'log10', 'noiseParameter1_observable_0ac': 'log10', 'noiseParameter1_observable_4ac': 'log10', 'noiseParameter1_observable_k12': 'log10', 'noiseParameter1_observable_k12k16': 'log10', 'noiseParameter1_observable_k16': 'log10', 'noiseParameter1_observable_k5': 'log10', 'noiseParameter1_observable_k5k12': 'log10', 'noiseParameter1_observable_k5k12k16': 'log10', 'noiseParameter1_observable_k5k16': 'lin', 'noiseParameter1_observable_k5k8': 'log10', 'noiseParameter1_observable_k5k8k12': 'log10', 'noiseParameter1_observable_k5k8k16': 'log10', 'noiseParameter1_observable_k8': 'log10', 'noiseParameter1_observable_k8k12': 'log10', 'noiseParameter1_observable_k8k12k16': 'log10', 'noiseParameter1_observable_k8k16': 'log10'})
2026-06-29 07:09:25.508 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:09:25.510 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'d': np.float64(0.0)}
2026-06-29 07:09:25.510 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:09:25.511 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'a_k8': 'a_k8', 'a_k5_k5k12': 'a_k5_k5k12', 'a_k12_k5k12': 'a_k12_k5k12', 'a_k16_k12k16': 'a_k16_k12k16', 'a_k5k12_k5k8k12': 'a_k5k12_k5k8k12', 'a_k12k16_k8k12k16': 'a_k12k16_k8k12k16', 'a_k8k12k16_4ac': 'a_k8k12k16_4ac', 'a_basal': 'a_basal', 'noiseParameter1_observable_0ac': 'sigma', 'noiseParameter1_observable_4ac': 'sigma', 'noiseParameter1_observable_k12': 'sigma', 'noiseParameter1_observable_k12k16': 'sigma', 'noiseParameter1_observable_k16': 'sigma', 'noiseParameter1_observable_k5': 'sigma', 'noiseParameter1_observable_k5k12': 'sigma', 'noiseParameter1_observable_k5k12k16': 'sigma', 'noiseParameter1_observable_k5k16': nan, 'noiseParameter1_observable_k5k8': 'sigma', 'noiseParameter1_observable_k5k8k12': 'sigma', 'noiseParameter1_observable_k5k8k16': 'sigma', 'noiseParameter1_observable_k8': 'sigma', 'noiseParameter1_observable_k8k12': 'sigma', 'noiseParameter1_observable_k8k12k16': 'sigma', 'noiseParameter1_observable_k8k16': 'sigma'}
2026-06-29 07:09:25.512 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'a_k8': 'a_k8', 'a_k5_k5k12': 'a_k5_k5k12', 'a_k12_k5k12': 'a_k12_k5k12', 'a_k16_k12k16': 'a_k16_k12k16', 'a_k5k12_k5k8k12': 'a_k5k12_k5k8k12', 'a_k12k16_k8k12k16': 'a_k12k16_k8k12k16', 'a_k8k12k16_4ac': 'a_k8k12k16_4ac', 'a_basal': 'a_basal', 'noiseParameter1_observable_0ac': 'sigma', 'noiseParameter1_observable_4ac': 'sigma', 'noiseParameter1_observable_k12': 'sigma', 'noiseParameter1_observable_k12k16': 'sigma', 'noiseParameter1_observable_k16': 'sigma', 'noiseParameter1_observable_k5': 'sigma', 'noiseParameter1_observable_k5k12': 'sigma', 'noiseParameter1_observable_k5k12k16': 'sigma', 'noiseParameter1_observable_k5k16': nan, 'noiseParameter1_observable_k5k8': 'sigma', 'noiseParameter1_observable_k5k8k12': 'sigma', 'noiseParameter1_observable_k5k8k16': 'sigma', 'noiseParameter1_observable_k8': 'sigma', 'noiseParameter1_observable_k8k12': 'sigma', 'noiseParameter1_observable_k8k12k16': 'sigma', 'noiseParameter1_observable_k8k16': 'sigma'}
Status: ['AMICI_SUCCESS']
[20]:
# Remove conserved quantities - this requires re-importing the model

# this is enabled by the `AMICI_EXPERIMENTAL_SBML_NONCONST_CLS` environment variable
os.environ["AMICI_EXPERIMENTAL_SBML_NONCONST_CLS"] = "1"
amici_model = import_petab_problem(
    petab_problem,
    verbose=False,
    # we need a different model name if we import the model again
    # we cannot load a model with the same name as an already loaded model
    model_name="Blasi_CellSystems2016_2",
    compile_=True,
)
del os.environ["AMICI_EXPERIMENTAL_SBML_NONCONST_CLS"]

amici_solver = amici_model.create_solver()
amici_solver.set_sensitivity_method(SensitivityMethod.forward)
amici_solver.set_sensitivity_order(SensitivityOrder.first)

res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
    solver=amici_solver,
)
print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)
assert all(rdata.status == AMICI_SUCCESS for rdata in res[RDATAS])
2026-06-29 07:09:45.242 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({}, {'d': np.float64(0.0), 'a_k8': 'a_k8', 'a_k5_k5k12': 'a_k5_k5k12', 'a_k12_k5k12': 'a_k12_k5k12', 'a_k16_k12k16': 'a_k16_k12k16', 'a_k5k12_k5k8k12': 'a_k5k12_k5k8k12', 'a_k12k16_k8k12k16': 'a_k12k16_k8k12k16', 'a_k8k12k16_4ac': 'a_k8k12k16_4ac', 'a_basal': 'a_basal', 'noiseParameter1_observable_0ac': 'sigma', 'noiseParameter1_observable_4ac': 'sigma', 'noiseParameter1_observable_k12': 'sigma', 'noiseParameter1_observable_k12k16': 'sigma', 'noiseParameter1_observable_k16': 'sigma', 'noiseParameter1_observable_k5': 'sigma', 'noiseParameter1_observable_k5k12': 'sigma', 'noiseParameter1_observable_k5k12k16': 'sigma', 'noiseParameter1_observable_k5k16': nan, 'noiseParameter1_observable_k5k8': 'sigma', 'noiseParameter1_observable_k5k8k12': 'sigma', 'noiseParameter1_observable_k5k8k16': 'sigma', 'noiseParameter1_observable_k8': 'sigma', 'noiseParameter1_observable_k8k12': 'sigma', 'noiseParameter1_observable_k8k12k16': 'sigma', 'noiseParameter1_observable_k8k16': 'sigma'}, {}, {'d': 'log10', 'a_k8': 'log10', 'a_k5_k5k12': 'log10', 'a_k12_k5k12': 'log10', 'a_k16_k12k16': 'log10', 'a_k5k12_k5k8k12': 'log10', 'a_k12k16_k8k12k16': 'log10', 'a_k8k12k16_4ac': 'log10', 'a_basal': 'log10', 'noiseParameter1_observable_0ac': 'log10', 'noiseParameter1_observable_4ac': 'log10', 'noiseParameter1_observable_k12': 'log10', 'noiseParameter1_observable_k12k16': 'log10', 'noiseParameter1_observable_k16': 'log10', 'noiseParameter1_observable_k5': 'log10', 'noiseParameter1_observable_k5k12': 'log10', 'noiseParameter1_observable_k5k12k16': 'log10', 'noiseParameter1_observable_k5k16': 'lin', 'noiseParameter1_observable_k5k8': 'log10', 'noiseParameter1_observable_k5k8k12': 'log10', 'noiseParameter1_observable_k5k8k16': 'log10', 'noiseParameter1_observable_k8': 'log10', 'noiseParameter1_observable_k8k12': 'log10', 'noiseParameter1_observable_k8k12k16': 'log10', 'noiseParameter1_observable_k8k16': 'log10'})
2026-06-29 07:09:45.243 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {}
2026-06-29 07:09:45.244 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'d': np.float64(0.0)}
2026-06-29 07:09:45.245 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {}
2026-06-29 07:09:45.246 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'a_k8': 'a_k8', 'a_k5_k5k12': 'a_k5_k5k12', 'a_k12_k5k12': 'a_k12_k5k12', 'a_k16_k12k16': 'a_k16_k12k16', 'a_k5k12_k5k8k12': 'a_k5k12_k5k8k12', 'a_k12k16_k8k12k16': 'a_k12k16_k8k12k16', 'a_k8k12k16_4ac': 'a_k8k12k16_4ac', 'a_basal': 'a_basal', 'noiseParameter1_observable_0ac': 'sigma', 'noiseParameter1_observable_4ac': 'sigma', 'noiseParameter1_observable_k12': 'sigma', 'noiseParameter1_observable_k12k16': 'sigma', 'noiseParameter1_observable_k16': 'sigma', 'noiseParameter1_observable_k5': 'sigma', 'noiseParameter1_observable_k5k12': 'sigma', 'noiseParameter1_observable_k5k12k16': 'sigma', 'noiseParameter1_observable_k5k16': nan, 'noiseParameter1_observable_k5k8': 'sigma', 'noiseParameter1_observable_k5k8k12': 'sigma', 'noiseParameter1_observable_k5k8k16': 'sigma', 'noiseParameter1_observable_k8': 'sigma', 'noiseParameter1_observable_k8k12': 'sigma', 'noiseParameter1_observable_k8k12k16': 'sigma', 'noiseParameter1_observable_k8k16': 'sigma'}
2026-06-29 07:09:45.247 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'a_k8': 'a_k8', 'a_k5_k5k12': 'a_k5_k5k12', 'a_k12_k5k12': 'a_k12_k5k12', 'a_k16_k12k16': 'a_k16_k12k16', 'a_k5k12_k5k8k12': 'a_k5k12_k5k8k12', 'a_k12k16_k8k12k16': 'a_k12k16_k8k12k16', 'a_k8k12k16_4ac': 'a_k8k12k16_4ac', 'a_basal': 'a_basal', 'noiseParameter1_observable_0ac': 'sigma', 'noiseParameter1_observable_4ac': 'sigma', 'noiseParameter1_observable_k12': 'sigma', 'noiseParameter1_observable_k12k16': 'sigma', 'noiseParameter1_observable_k16': 'sigma', 'noiseParameter1_observable_k5': 'sigma', 'noiseParameter1_observable_k5k12': 'sigma', 'noiseParameter1_observable_k5k12k16': 'sigma', 'noiseParameter1_observable_k5k16': nan, 'noiseParameter1_observable_k5k8': 'sigma', 'noiseParameter1_observable_k5k8k12': 'sigma', 'noiseParameter1_observable_k5k8k16': 'sigma', 'noiseParameter1_observable_k8': 'sigma', 'noiseParameter1_observable_k8k12': 'sigma', 'noiseParameter1_observable_k8k12k16': 'sigma', 'noiseParameter1_observable_k8k16': 'sigma'}
Status: ['AMICI_SUCCESS']

Steady state computation failed

Let’s run a simulation:

[21]:
petab_problem = benchmark_models_petab.get_problem("Brannmark_JBC2010")
amici_model = import_petab_problem(
    petab_problem,
    verbose=False,
)

amici_solver = amici_model.create_solver()


np.random.seed(1851)
problem_parameters = dict(
    zip(
        petab_problem.x_free_ids,
        petab_problem.sample_parameter_startpoints(n_starts=1)[0],
    )
)
res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
    solver=amici_solver,
)

print(
    "Status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)

# hard to reproduce on GHA
if os.getenv("GITHUB_ACTIONS") is None:
    assert [
        simulation_status_to_str(rdata.status) for rdata in res[RDATAS]
    ] == [
        "AMICI_ERROR",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
    ]
2026-06-29 07:10:03.124 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.125 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.125 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.126 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.127 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.128 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.128 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.129 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.129 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.130 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.130 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.131 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.132 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.132 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.133 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.133 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.134 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.134 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.135 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.135 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.137 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.137 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.138 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.138 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.139 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.139 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.140 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.140 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.141 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.141 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.142 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.143 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.143 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.144 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.144 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.145 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.145 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.146 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.146 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.147 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.147 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.148 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.148 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'})
2026-06-29 07:10:03.149 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.150 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8}
2026-06-29 07:10:03.150 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.151 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.151 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.218 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][cvodes:cvHandleFailure:ERR_FAILURE] At t = 736.713 and h = 0.000145837, the error test failed repeatedly or with |h| = hmin.
2026-06-29 07:10:03.219 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][OTHER] AMICI equilibration failed at t=736.713.
2026-06-29 07:10:03.220 - amici.sim.sundials._swig_wrappers - ERROR - [Dose_0+Dose_0][OTHER] AMICI simulation failed: Steady state computation failed. Simulation to steady state failed.
Status: ['AMICI_ERROR', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN']

What happened?

All given experimental conditions require pre-equilibration, i.e., finding a steady state. AMICI first tries to find a steady state using the Newton solver, if that fails, it tries simulating until steady state, if that also fails, it tries the Newton solver from the end of the simulation. In this case, all three failed. Neither Newton’s method nor simulation yielded a steady state satisfying the required tolerances.

This can also be seen in ReturnDataView.preeq_status (the three statuses corresponds to Newton #1, Simulation, Newton #2):

[22]:
rdata = res[RDATAS][0]
rdata.preeq_status
[22]:
[<SteadyStateStatus.not_run: 0>,
 <SteadyStateStatus.failed: -1>,
 <SteadyStateStatus.not_run: 0>]

How to address?

There are several ways to address that:

  1. Stricter integration tolerances (preferred if affordable - higher accuracy, but generally slower)

  2. Looser steady-state tolerances (lower accuracy, generally faster)

  3. Increase the number of allowed steps for Newton’s method

Let’s try all of them:

[23]:
# Reduce relative tolerance for integration
amici_solver = amici_model.create_solver()
amici_solver.set_relative_tolerance(
    1 / 100 * amici_solver.get_relative_tolerance(),
)

res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
    solver=amici_solver,
)
print(
    "status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)

rdata = res[RDATAS][0]
print(f"preeq_status={rdata.preeq_status}")
print(f"{rdata.preeq_numsteps=}")

# hard to reproduce on GHA
if os.getenv("GITHUB_ACTIONS") is None:
    assert all(rdata.status == AMICI_SUCCESS for rdata in res[RDATAS])
2026-06-29 07:10:03.352 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.353 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.354 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.355 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.356 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.356 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.357 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.358 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.359 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.359 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.359 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.360 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.361 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.361 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.362 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.362 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.363 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.363 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.364 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.365 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.365 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.365 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.366 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.366 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.367 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.368 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.368 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.369 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.369 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.370 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.370 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.371 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.373 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.373 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.374 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.374 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.375 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.376 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.376 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.376 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.377 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.377 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.378 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'})
2026-06-29 07:10:03.379 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.379 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8}
2026-06-29 07:10:03.380 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.380 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.381 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
status: ['AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS']
preeq_status=[<SteadyStateStatus.not_run: 0>, <SteadyStateStatus.success: 1>, <SteadyStateStatus.not_run: 0>]
rdata.preeq_numsteps=array([   0, 3150,    0])
[24]:
# Increase relative steady state tolerance
for log10_relaxation_factor in range(1, 10):
    print(f"Relaxing tolerances by factor {10**log10_relaxation_factor}")
    amici_solver = amici_model.create_solver()
    amici_solver.set_relative_tolerance_steady_state(
        amici_solver.get_relative_tolerance_steady_state()
        * 10**log10_relaxation_factor
    )

    res = simulate_petab(
        petab_problem=petab_problem,
        amici_model=amici_model,
        problem_parameters=problem_parameters,
        scaled_parameters=True,
        solver=amici_solver,
    )
    if all(rdata.status == AMICI_SUCCESS for rdata in res[RDATAS]):
        print(
            f"-> Succeeded with relative steady state tolerance {amici_solver.get_relative_tolerance_steady_state()}\n"
        )
        break
    else:
        print("-> Failed.\n")

print(
    "status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)

rdata = res[RDATAS][0]
print(f"preeq_status={rdata.preeq_status}")
print(f"{rdata.preeq_numsteps=}")
assert all(rdata.status == AMICI_SUCCESS for rdata in res[RDATAS])
2026-06-29 07:10:03.587 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.588 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.588 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.589 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.589 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.590 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.591 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.591 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.592 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.592 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.593 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.593 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.594 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.594 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.595 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.595 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.596 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.596 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.597 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.598 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.598 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.599 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.599 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.600 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.600 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.601 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.601 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.602 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.602 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.603 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.603 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.605 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.605 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.606 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.606 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.607 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.607 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.608 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.609 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.609 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.609 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.610 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.611 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'})
2026-06-29 07:10:03.611 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.612 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8}
2026-06-29 07:10:03.612 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.613 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.613 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.681 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][cvodes:cvHandleFailure:ERR_FAILURE] At t = 736.713 and h = 0.000145837, the error test failed repeatedly or with |h| = hmin.
2026-06-29 07:10:03.682 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][OTHER] AMICI equilibration failed at t=736.713.
2026-06-29 07:10:03.682 - amici.sim.sundials._swig_wrappers - ERROR - [Dose_0+Dose_0][OTHER] AMICI simulation failed: Steady state computation failed. Simulation to steady state failed.
Relaxing tolerances by factor 10
-> Failed.

Relaxing tolerances by factor 100
2026-06-29 07:10:03.784 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.785 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.786 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.787 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.788 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.788 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.789 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.790 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.791 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.792 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.792 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.793 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.793 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.794 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.794 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.795 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.796 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.796 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.797 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.798 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.800 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.800 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.801 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.802 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.802 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.803 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.804 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.805 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.805 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.806 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.806 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.807 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.808 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.808 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.809 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.809 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.810 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.810 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.811 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.811 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.812 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.813 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.813 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'})
2026-06-29 07:10:03.815 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.815 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8}
2026-06-29 07:10:03.815 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.816 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.816 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:03.881 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][cvodes:cvHandleFailure:ERR_FAILURE] At t = 736.713 and h = 0.000145837, the error test failed repeatedly or with |h| = hmin.
2026-06-29 07:10:03.882 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][OTHER] AMICI equilibration failed at t=736.713.
2026-06-29 07:10:03.882 - amici.sim.sundials._swig_wrappers - ERROR - [Dose_0+Dose_0][OTHER] AMICI simulation failed: Steady state computation failed. Simulation to steady state failed.
2026-06-29 07:10:03.978 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.979 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.979 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.981 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.981 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.982 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.982 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.983 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.984 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.984 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.985 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.985 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.986 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.988 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.989 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.989 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.990 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.990 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.991 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.992 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.993 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.993 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.994 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.995 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.995 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:03.996 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.997 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:03.997 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.998 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.998 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:03.999 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.000 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.000 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.001 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.001 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.002 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.002 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.005 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.005 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.006 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.007 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.007 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.008 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'})
2026-06-29 07:10:04.009 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.009 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8}
2026-06-29 07:10:04.010 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:04.010 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:04.011 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:04.079 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][cvodes:cvHandleFailure:ERR_FAILURE] At t = 736.713 and h = 0.000145837, the error test failed repeatedly or with |h| = hmin.
2026-06-29 07:10:04.080 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][OTHER] AMICI equilibration failed at t=736.713.
2026-06-29 07:10:04.081 - amici.sim.sundials._swig_wrappers - ERROR - [Dose_0+Dose_0][OTHER] AMICI simulation failed: Steady state computation failed. Simulation to steady state failed.
-> Failed.

Relaxing tolerances by factor 1000
-> Failed.

Relaxing tolerances by factor 10000
2026-06-29 07:10:04.189 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.190 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.191 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.191 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.192 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.193 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.194 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.194 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.195 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.195 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.196 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.196 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.197 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.197 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.198 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.198 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.199 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.199 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.200 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.201 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.201 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.202 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.202 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.203 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.204 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.204 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.205 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.205 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.206 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.206 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.207 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.209 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.209 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.210 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.210 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.211 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.212 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.212 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.213 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.213 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.214 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.214 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.215 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'})
2026-06-29 07:10:04.216 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.216 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8}
2026-06-29 07:10:04.217 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:04.217 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:04.218 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
-> Succeeded with relative steady state tolerance 0.01

status: ['AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS', 'AMICI_SUCCESS']
preeq_status=[<SteadyStateStatus.not_run: 0>, <SteadyStateStatus.success: 1>, <SteadyStateStatus.not_run: 0>]
rdata.preeq_numsteps=array([  0, 577,   0])

That fixed the error, and took only a quarter of the number steps as the previous run, but at the cost of much lower accuracy.

[25]:
# Let's try increasing the number of Newton steps
# (this is 0 by default, so the Newton solver wasn't used before,
#  as can be seen from the 0 in `rdata.preeq_numsteps[0]`)
amici_solver = amici_model.create_solver()
amici_solver.set_newton_max_steps(10**4)

res = simulate_petab(
    petab_problem=petab_problem,
    amici_model=amici_model,
    problem_parameters=problem_parameters,
    scaled_parameters=True,
    solver=amici_solver,
)
print(
    "status:",
    [simulation_status_to_str(rdata.status) for rdata in res[RDATAS]],
)

rdata = res[RDATAS][0]
print(f"preeq_status={rdata.preeq_status}")
print(f"{rdata.preeq_numsteps=}")
# hard to reproduce on GHA
if os.getenv("GITHUB_ACTIONS") is None:
    assert [
        simulation_status_to_str(rdata.status) for rdata in res[RDATAS]
    ] == [
        "AMICI_ERROR",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
        "AMICI_NOT_RUN",
    ]
2026-06-29 07:10:04.407 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.408 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.408 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.409 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.410 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.411 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.411 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.412 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.413 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.01, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.413 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.414 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.414 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.415 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.416 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.416 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.1, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.417 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.417 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.418 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.418 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.419 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.420 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.3, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.420 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.421 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.421 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.422 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.423 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.423 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 10.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.423 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.424 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.425 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.425 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'log10', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'log10', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.426 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.426 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 100.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.427 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.427 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.428 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': 'k_IRP_1Step', 'observableParameter1_IRS1_P': 'k_IRSiP_1Step', 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': 'sigmaY1TimR', 'noiseParameter1_IRS1_P': 'sigmaY2TimR', 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.429 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'lin', 'observableParameter1_IRS1_P_DosR': 'log10', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'lin', 'noiseParameter1_IRS1_P_DosR': 'log10'})
2026-06-29 07:10:04.429 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.430 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 1.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.430 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.431 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.431 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': nan, 'observableParameter1_IRS1_P_DosR': 'k_IRSiP_DosR', 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': nan, 'noiseParameter1_IRS1_P_DosR': 'sigmaYDosR'}
2026-06-29 07:10:04.432 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - PEtab mapping: ({'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8, 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'}, {'k1a': 'log10', 'k1aBasic': 'log10', 'k1b': 'log10', 'k1c': 'log10', 'k1d': 'log10', 'k1e': 'log10', 'k1f': 'log10', 'k1g': 'log10', 'k1r': 'log10', 'k21': 'log10', 'k22': 'log10', 'k3': 'log10', 'k_IRSiP_DosR': 'log10', 'km2': 'log10', 'km3': 'log10', 'insulin_time_1': 'lin', 'insulin_time_2': 'lin', 'insulin_dose_1': 'lin', 'insulin_dose_2': 'lin', 'observableParameter1_IR1_P': 'lin', 'observableParameter1_IRS1_P': 'log10', 'observableParameter1_IRS1_P_DosR': 'lin', 'noiseParameter1_IR1_P': 'lin', 'noiseParameter1_IRS1_P': 'log10', 'noiseParameter1_IRS1_P_DosR': 'lin'})
2026-06-29 07:10:04.433 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters pre-equilibration: {'insulin_time_1': 0.0, 'insulin_time_2': 0.0, 'insulin_dose_1': 0.0, 'insulin_dose_2': 0.0}
2026-06-29 07:10:04.433 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Fixed parameters simulation: {'insulin_time_1': 0.0, 'insulin_time_2': 4.0, 'insulin_dose_1': 1.2, 'insulin_dose_2': 8.8}
2026-06-29 07:10:04.434 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters pre-equilibration: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:04.434 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Variable parameters simulation: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:04.435 - amici.sim.sundials.petab.v1._parameter_mapping - DEBUG - Merged: {'k1a': 'k1a', 'k1aBasic': 'k1aBasic', 'k1b': 'k1b', 'k1c': 'k1c', 'k1d': 'k1d', 'k1e': 'k1e', 'k1f': 'k1f', 'k1g': 'k1g', 'k1r': 'k1r', 'k21': 'k21', 'k22': 'k22', 'k3': 'k3', 'k_IRSiP_DosR': 'k_IRSiP_DosR', 'km2': 'km2', 'km3': 'km3', 'observableParameter1_IR1_P': nan, 'observableParameter1_IRS1_P': 'k_IRSiP_2Step', 'observableParameter1_IRS1_P_DosR': nan, 'noiseParameter1_IR1_P': nan, 'noiseParameter1_IRS1_P': 'sigmaY2Step', 'noiseParameter1_IRS1_P_DosR': nan}
2026-06-29 07:10:04.507 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][cvodes:cvHandleFailure:ERR_FAILURE] At t = 736.713 and h = 0.000145837, the error test failed repeatedly or with |h| = hmin.
2026-06-29 07:10:04.508 - amici.sim.sundials._swig_wrappers - DEBUG - [Dose_0+Dose_0][OTHER] AMICI equilibration failed at t=736.713.
2026-06-29 07:10:04.508 - amici.sim.sundials._swig_wrappers - ERROR - [Dose_0+Dose_0][OTHER] AMICI simulation failed: Steady state computation failed. Simulation to steady state failed.
status: ['AMICI_ERROR', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN', 'AMICI_NOT_RUN']
preeq_status=[<SteadyStateStatus.not_run: 0>, <SteadyStateStatus.failed: -1>, <SteadyStateStatus.not_run: 0>]
rdata.preeq_numsteps=array([   0, 1105,    0])

Increasing the maximum number of Newton steps doesn’t seem to help here. The Jacobian was numerically singular and its factorization failed. This can be a result of conserved quantities in the model. Section Steady state sensitivity computation failed due to unsuccessful factorization of RHS Jacobian shows how to address that.