Doxorubicin addition test

using ProgressLogging
using OrdinaryDiffEq
using ModelingToolkit
using Plots
using DisplayAs: PNG
using ECMEDox
using ECMEDox: second, mM, Hz, μM, build_stim_callbacks
Plots.default(lw=1.5, size=(600, 600))
tend = 1000.0second
bcl = 1second
@named sys = build_model()
@unpack DOX = sys
sts = unknowns(sys)
u0 = build_u0(sys)
alg = KenCarp47()
@unpack iStim = sys
callback = build_stim_callbacks(iStim, tend; period=bcl)
opts = (; reltol=1e-6, abstol=1e-6, progress=true, callback=callback, saveat=1.0second)
prob = ODEProblem(sys, u0, tend)
ODEProblem with uType Vector{Float64} and tType Float64. In-place: true
Initialization status: FULLY_DETERMINED
Non-trivial mass matrix: false
timespan: (0.0, 1.0e6)
u0: 64-element Vector{Float64}:
      2.196435053752864
      0.0007273589705197244
      0.000981691808598968
    245.22202099807583
    281.0719264404058
    197.06621753790645
     34.41477140951692
     60.37913837798986
    229.2919970960533
     22.321405235243013
      ⋮
     23.148552252520883
      0.6928662120941113
      0.20648605639609985
   1295.5364065086924
   1299.7940884726063
      0.20381438659933854
 145551.11317854663
  10276.480036234318
    -85.29107641956527

The collapse of MMP is between 290uM and 300uM of DOX

doxrange = 290μM:1μM:300μM
prob_func = (prob, i, repeat) -> begin
    prob.ps[DOX] = doxrange[i]
    prob
end
#2 (generic function with 1 method)
eprob = EnsembleProblem(prob; prob_func)
@time sim = solve(eprob, alg; trajectories=length(doxrange), opts...)
321.709365 seconds (129.35 M allocations: 13.742 GiB, 0.76% gc time, 5.14% compilation time)
EnsembleSolution Solution of length 11 with uType:
SciMLBase.ODESolution{Float64, 2, Vector{Vector{Float64}}, Nothing, Nothing, Vector{Float64}, Vector{Vector{Vector{Float64}}}, Nothing, SciMLBase.ODEProblem{Vector{Float64}, Tuple{Float64, Float64}, true, ModelingToolkit.MTKParameters{Vector{Float64}, Vector{Float64}, Tuple{}, Tuple{}, Tuple{}, Tuple{}}, SciMLBase.ODEFunction{true, SciMLBase.FullSpecialize, ModelingToolkit.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x234e52b3, 0xee1a17de, 0xbf459d9b, 0x7f20b256, 0x0d9ac8b1), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x72543ba4, 0x23d85303, 0x16090aba, 0x08bfb49f, 0x76f6c515), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkit.ObservedFunctionCache{ModelingToolkit.System}, Nothing, ModelingToolkit.System, SciMLBase.OverrideInitData{SciMLBase.NonlinearProblem{Nothing, true, ModelingToolkit.MTKParameters{Vector{Float64}, StaticArraysCore.SVector{0, Float64}, Tuple{}, Tuple{}, Tuple{}, Tuple{}}, SciMLBase.NonlinearFunction{true, SciMLBase.FullSpecialize, ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xdddcfdeb, 0x34ea441c, 0x9d13c31f, 0xe0898c04, 0x1139e68d), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x33f8209c, 0xca3f1431, 0x785cf31d, 0xa154e4b6, 0x8371f0fb), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkit.ObservedFunctionCache{ModelingToolkit.System}, Nothing, ModelingToolkit.System, Nothing, Nothing}, Base.Pairs{Symbol, Union{}, Nothing, @NamedTuple{}}, SciMLBase.StandardNonlinearProblem, Nothing, Nothing}, typeof(ModelingToolkit.update_initializeprob!), ComposedFunction{ComposedFunction{typeof(identity), typeof(ModelingToolkit.safe_float)}, SymbolicIndexingInterface.TimeIndependentObservedFunction{ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xd5689313, 0x9ab4b22c, 0xbcc06553, 0xd81b7676, 0x2d9abab2), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xae6a07ca, 0x86506090, 0xfdf9f188, 0x35b4f95d, 0xbe5c4722), Nothing}}}}, ModelingToolkit.var"#initprobpmap_split#977"{ModelingToolkit.var"#_getter#973"{Tuple{ComposedFunction{ModelingToolkit.PConstructorApplicator{typeof(identity)}, ModelingToolkit.ObservedWrapper{false, ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x29c443c0, 0xb7a00f5b, 0x57cfcb7a, 0x51b2c355, 0xfc48ecce), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xd3dd2c86, 0x5732d974, 0xa743de83, 0xb6f746d8, 0x53ca0d35), Nothing}}}}, ComposedFunction{ModelingToolkit.PConstructorApplicator{typeof(identity)}, ModelingToolkit.ObservedWrapper{false, ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x6e8ebc58, 0xba920411, 0xcd48896e, 0x4e48f455, 0xfeb38e3e), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x4a1bf9f5, 0xeb633633, 0x383968af, 0x364a6f25, 0x91ca6263), Nothing}}}}, Returns{Tuple{}}, Returns{Tuple{}}, Returns{Tuple{}}}}}, ModelingToolkit.InitializationMetadata{ModelingToolkit.ReconstructInitializeprob{ModelingToolkit.var"#_getter#973"{Tuple{ComposedFunction{ModelingToolkit.PConstructorApplicator{typeof(identity)}, ModelingToolkit.ObservedWrapper{true, ModelingToolkit.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x1424b757, 0x85fc99b9, 0x8fa6b3f1, 0x38e68903, 0xba15fd6f), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x150f27e6, 0x62d66c8b, 0x07b34db7, 0x977dcca4, 0x1773c4f5), Nothing}}}}, Returns{StaticArraysCore.SVector{0, Float64}}, Returns{Tuple{}}, Returns{Tuple{}}, Returns{Tuple{}}}}, ComposedFunction{typeof(identity), ModelingToolkit.ObservedWrapper{true, ModelingToolkit.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x949bdd90, 0xaee9a3b6, 0x251c9a2f, 0x9c60f2b7, 0xd605c55d), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x8fc4dc42, 0xab19a0c7, 0x7dc77568, 0x6a4f78c4, 0xf2705f06), Nothing}}}}}, ModelingToolkit.GetUpdatedU0{SymbolicIndexingInterface.MultipleGetters{SymbolicIndexingInterface.ContinuousTimeseries, Vector{SymbolicUtils.BasicSymbolic{Real}}}, SymbolicIndexingInterface.MultipleParametersGetter{SymbolicIndexingInterface.IndexerNotTimeseries, Vector{SymbolicIndexingInterface.GetParameterIndex{ModelingToolkit.ParameterIndex{SciMLStructures.Initials, Int64}}}, Nothing}}, ModelingToolkit.SetInitialUnknowns{SymbolicIndexingInterface.MultipleSetters{Vector{SymbolicIndexingInterface.ParameterHookWrapper{SymbolicIndexingInterface.SetParameterIndex{ModelingToolkit.ParameterIndex{SciMLStructures.Initials, Int64}}, SymbolicUtils.BasicSymbolic{Real}}}}}}, Val{true}}, Nothing}, Base.Pairs{Symbol, Union{}, Nothing, @NamedTuple{}}, SciMLBase.StandardODEProblem}, OrdinaryDiffEqSDIRK.KenCarp47{0, ADTypes.AutoForwardDiff{nothing, ForwardDiff.Tag{DiffEqBase.OrdinaryDiffEqTag, Float64}}, Nothing, OrdinaryDiffEqNonlinearSolve.NLNewton{Rational{Int64}, Rational{Int64}, Rational{Int64}, Nothing}, typeof(OrdinaryDiffEqCore.DEFAULT_PRECS), Val{:forward}(), true, nothing}, OrdinaryDiffEqCore.InterpolationData{SciMLBase.ODEFunction{true, SciMLBase.FullSpecialize, ModelingToolkit.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x234e52b3, 0xee1a17de, 0xbf459d9b, 0x7f20b256, 0x0d9ac8b1), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x72543ba4, 0x23d85303, 0x16090aba, 0x08bfb49f, 0x76f6c515), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkit.ObservedFunctionCache{ModelingToolkit.System}, Nothing, ModelingToolkit.System, SciMLBase.OverrideInitData{SciMLBase.NonlinearProblem{Nothing, true, ModelingToolkit.MTKParameters{Vector{Float64}, StaticArraysCore.SVector{0, Float64}, Tuple{}, Tuple{}, Tuple{}, Tuple{}}, SciMLBase.NonlinearFunction{true, SciMLBase.FullSpecialize, ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xdddcfdeb, 0x34ea441c, 0x9d13c31f, 0xe0898c04, 0x1139e68d), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x33f8209c, 0xca3f1431, 0x785cf31d, 0xa154e4b6, 0x8371f0fb), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkit.ObservedFunctionCache{ModelingToolkit.System}, Nothing, ModelingToolkit.System, Nothing, Nothing}, Base.Pairs{Symbol, Union{}, Nothing, @NamedTuple{}}, SciMLBase.StandardNonlinearProblem, Nothing, Nothing}, typeof(ModelingToolkit.update_initializeprob!), ComposedFunction{ComposedFunction{typeof(identity), typeof(ModelingToolkit.safe_float)}, SymbolicIndexingInterface.TimeIndependentObservedFunction{ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xd5689313, 0x9ab4b22c, 0xbcc06553, 0xd81b7676, 0x2d9abab2), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xae6a07ca, 0x86506090, 0xfdf9f188, 0x35b4f95d, 0xbe5c4722), Nothing}}}}, ModelingToolkit.var"#initprobpmap_split#977"{ModelingToolkit.var"#_getter#973"{Tuple{ComposedFunction{ModelingToolkit.PConstructorApplicator{typeof(identity)}, ModelingToolkit.ObservedWrapper{false, ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x29c443c0, 0xb7a00f5b, 0x57cfcb7a, 0x51b2c355, 0xfc48ecce), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xd3dd2c86, 0x5732d974, 0xa743de83, 0xb6f746d8, 0x53ca0d35), Nothing}}}}, ComposedFunction{ModelingToolkit.PConstructorApplicator{typeof(identity)}, ModelingToolkit.ObservedWrapper{false, ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x6e8ebc58, 0xba920411, 0xcd48896e, 0x4e48f455, 0xfeb38e3e), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x4a1bf9f5, 0xeb633633, 0x383968af, 0x364a6f25, 0x91ca6263), Nothing}}}}, Returns{Tuple{}}, Returns{Tuple{}}, Returns{Tuple{}}}}}, ModelingToolkit.InitializationMetadata{ModelingToolkit.ReconstructInitializeprob{ModelingToolkit.var"#_getter#973"{Tuple{ComposedFunction{ModelingToolkit.PConstructorApplicator{typeof(identity)}, ModelingToolkit.ObservedWrapper{true, ModelingToolkit.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x1424b757, 0x85fc99b9, 0x8fa6b3f1, 0x38e68903, 0xba15fd6f), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x150f27e6, 0x62d66c8b, 0x07b34db7, 0x977dcca4, 0x1773c4f5), Nothing}}}}, Returns{StaticArraysCore.SVector{0, Float64}}, Returns{Tuple{}}, Returns{Tuple{}}, Returns{Tuple{}}}}, ComposedFunction{typeof(identity), ModelingToolkit.ObservedWrapper{true, ModelingToolkit.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x949bdd90, 0xaee9a3b6, 0x251c9a2f, 0x9c60f2b7, 0xd605c55d), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x8fc4dc42, 0xab19a0c7, 0x7dc77568, 0x6a4f78c4, 0xf2705f06), Nothing}}}}}, ModelingToolkit.GetUpdatedU0{SymbolicIndexingInterface.MultipleGetters{SymbolicIndexingInterface.ContinuousTimeseries, Vector{SymbolicUtils.BasicSymbolic{Real}}}, SymbolicIndexingInterface.MultipleParametersGetter{SymbolicIndexingInterface.IndexerNotTimeseries, Vector{SymbolicIndexingInterface.GetParameterIndex{ModelingToolkit.ParameterIndex{SciMLStructures.Initials, Int64}}}, Nothing}}, ModelingToolkit.SetInitialUnknowns{SymbolicIndexingInterface.MultipleSetters{Vector{SymbolicIndexingInterface.ParameterHookWrapper{SymbolicIndexingInterface.SetParameterIndex{ModelingToolkit.ParameterIndex{SciMLStructures.Initials, Int64}}, SymbolicUtils.BasicSymbolic{Real}}}}}}, Val{true}}, Nothing}, Vector{Vector{Float64}}, Vector{Float64}, Vector{Vector{Vector{Float64}}}, Nothing, cacheType, Nothing}, SciMLBase.DEStats, Nothing, Nothing, Nothing, Nothing} where cacheType<:(OrdinaryDiffEqSDIRK.KenCarp47Cache{Vector{Float64}, Vector{Float64}, Vector{Float64}, N, OrdinaryDiffEqSDIRK.KenCarp47Tableau{Float64, Float64}, Nothing} where N<:(OrdinaryDiffEqNonlinearSolve.NLSolver{OrdinaryDiffEqNonlinearSolve.NLNewton{Rational{Int64}, Rational{Int64}, Rational{Int64}, Nothing}, true, Vector{Float64}, Float64, Nothing, Float64, OrdinaryDiffEqNonlinearSolve.NLNewtonCache{Vector{Float64}, Float64, Float64, Vector{Float64}, Matrix{Float64}, Matrix{Float64}, SciMLBase.UJacobianWrapper{true, SciMLBase.ODEFunction{true, SciMLBase.FullSpecialize, ModelingToolkit.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x234e52b3, 0xee1a17de, 0xbf459d9b, 0x7f20b256, 0x0d9ac8b1), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x72543ba4, 0x23d85303, 0x16090aba, 0x08bfb49f, 0x76f6c515), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkit.ObservedFunctionCache{ModelingToolkit.System}, Nothing, ModelingToolkit.System, SciMLBase.OverrideInitData{SciMLBase.NonlinearProblem{Nothing, true, ModelingToolkit.MTKParameters{Vector{Float64}, StaticArraysCore.SVector{0, Float64}, Tuple{}, Tuple{}, Tuple{}, Tuple{}}, SciMLBase.NonlinearFunction{true, SciMLBase.FullSpecialize, ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xdddcfdeb, 0x34ea441c, 0x9d13c31f, 0xe0898c04, 0x1139e68d), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x33f8209c, 0xca3f1431, 0x785cf31d, 0xa154e4b6, 0x8371f0fb), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkit.ObservedFunctionCache{ModelingToolkit.System}, Nothing, ModelingToolkit.System, Nothing, Nothing}, Base.Pairs{Symbol, Union{}, Nothing, @NamedTuple{}}, SciMLBase.StandardNonlinearProblem, Nothing, Nothing}, typeof(ModelingToolkit.update_initializeprob!), ComposedFunction{ComposedFunction{typeof(identity), typeof(ModelingToolkit.safe_float)}, SymbolicIndexingInterface.TimeIndependentObservedFunction{ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xd5689313, 0x9ab4b22c, 0xbcc06553, 0xd81b7676, 0x2d9abab2), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xae6a07ca, 0x86506090, 0xfdf9f188, 0x35b4f95d, 0xbe5c4722), Nothing}}}}, ModelingToolkit.var"#initprobpmap_split#977"{ModelingToolkit.var"#_getter#973"{Tuple{ComposedFunction{ModelingToolkit.PConstructorApplicator{typeof(identity)}, ModelingToolkit.ObservedWrapper{false, ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x29c443c0, 0xb7a00f5b, 0x57cfcb7a, 0x51b2c355, 0xfc48ecce), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0xd3dd2c86, 0x5732d974, 0xa743de83, 0xb6f746d8, 0x53ca0d35), Nothing}}}}, ComposedFunction{ModelingToolkit.PConstructorApplicator{typeof(identity)}, ModelingToolkit.ObservedWrapper{false, ModelingToolkit.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x6e8ebc58, 0xba920411, 0xcd48896e, 0x4e48f455, 0xfeb38e3e), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x4a1bf9f5, 0xeb633633, 0x383968af, 0x364a6f25, 0x91ca6263), Nothing}}}}, Returns{Tuple{}}, Returns{Tuple{}}, Returns{Tuple{}}}}}, ModelingToolkit.InitializationMetadata{ModelingToolkit.ReconstructInitializeprob{ModelingToolkit.var"#_getter#973"{Tuple{ComposedFunction{ModelingToolkit.PConstructorApplicator{typeof(identity)}, ModelingToolkit.ObservedWrapper{true, ModelingToolkit.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x1424b757, 0x85fc99b9, 0x8fa6b3f1, 0x38e68903, 0xba15fd6f), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x150f27e6, 0x62d66c8b, 0x07b34db7, 0x977dcca4, 0x1773c4f5), Nothing}}}}, Returns{StaticArraysCore.SVector{0, Float64}}, Returns{Tuple{}}, Returns{Tuple{}}, Returns{Tuple{}}}}, ComposedFunction{typeof(identity), ModelingToolkit.ObservedWrapper{true, ModelingToolkit.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x949bdd90, 0xaee9a3b6, 0x251c9a2f, 0x9c60f2b7, 0xd605c55d), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkit.var"#_RGF_ModTag", ModelingToolkit.var"#_RGF_ModTag", (0x8fc4dc42, 0xab19a0c7, 0x7dc77568, 0x6a4f78c4, 0xf2705f06), Nothing}}}}}, ModelingToolkit.GetUpdatedU0{SymbolicIndexingInterface.MultipleGetters{SymbolicIndexingInterface.ContinuousTimeseries, Vector{SymbolicUtils.BasicSymbolic{Real}}}, SymbolicIndexingInterface.MultipleParametersGetter{SymbolicIndexingInterface.IndexerNotTimeseries, Vector{SymbolicIndexingInterface.GetParameterIndex{ModelingToolkit.ParameterIndex{SciMLStructures.Initials, Int64}}}, Nothing}}, ModelingToolkit.SetInitialUnknowns{SymbolicIndexingInterface.MultipleSetters{Vector{SymbolicIndexingInterface.ParameterHookWrapper{SymbolicIndexingInterface.SetParameterIndex{ModelingToolkit.ParameterIndex{SciMLStructures.Initials, Int64}}, SymbolicUtils.BasicSymbolic{Real}}}}}}, Val{true}}, Nothing}, Float64, ModelingToolkit.MTKParameters{Vector{Float64}, Vector{Float64}, Tuple{}, Tuple{}, Tuple{}, Tuple{}}}, jcType, LinearSolve.LinearCache{Matrix{Float64}, Vector{Float64}, Vector{Float64}, SciMLBase.NullParameters, LinearSolve.DefaultLinearSolver, LinearSolve.DefaultLinearSolverInit{LinearAlgebra.LU{Float64, Matrix{Float64}, Vector{Int64}}, LinearAlgebra.QRCompactWY{Float64, Matrix{Float64}, Matrix{Float64}}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Tuple{LinearAlgebra.LU{Float64, Matrix{Float64}, Vector{Int64}}, Vector{Int64}}, Tuple{LinearAlgebra.LU{Float64, Matrix{Float64}, Vector{Int64}}, Vector{Int64}}, Nothing, Nothing, Nothing, LinearAlgebra.SVD{Float64, Float64, Matrix{Float64}, Vector{Float64}}, LinearAlgebra.Cholesky{Float64, Matrix{Float64}}, LinearAlgebra.Cholesky{Float64, Matrix{Float64}}, Tuple{LinearAlgebra.LU{Float64, Matrix{Float64}, Vector{Int32}}, Base.RefValue{Int32}}, Tuple{LinearAlgebra.LU{Float64, Matrix{Float64}, Vector{Int64}}, Base.RefValue{Int64}}, LinearAlgebra.QRPivoted{Float64, Matrix{Float64}, Vector{Float64}, Vector{Int64}}, Nothing, Nothing, Nothing, Nothing, Nothing}, LinearSolve.InvPreconditioner{LinearAlgebra.Diagonal{Float64, Vector{Float64}}}, LinearAlgebra.Diagonal{Float64, Vector{Float64}}, Float64, LinearSolve.LinearVerbosity{SciMLLogging.Silent, SciMLLogging.Silent, SciMLLogging.Silent, SciMLLogging.Silent, SciMLLogging.CustomLevel, SciMLLogging.Silent, SciMLLogging.InfoLevel, SciMLLogging.Silent, SciMLLogging.WarnLevel, SciMLLogging.WarnLevel, SciMLLogging.Silent, SciMLLogging.Silent, SciMLLogging.Silent, SciMLLogging.WarnLevel, SciMLLogging.WarnLevel, SciMLLogging.WarnLevel}, Bool, LinearSolve.LinearSolveAdjoint{Missing}}}, Float64} where jcType<:Tuple{DifferentiationInterfaceForwardDiffExt.ForwardDiffTwoArgJacobianPrep{Nothing, C, Tuple{}} where C<:(ForwardDiff.JacobianConfig{ForwardDiff.Tag{DiffEqBase.OrdinaryDiffEqTag, Float64}, Float64, _A, <:Tuple{Array{ForwardDiff.Dual{ForwardDiff.Tag{DiffEqBase.OrdinaryDiffEqTag, Float64}, Float64, _A}, 1} where _A, Array{ForwardDiff.Dual{ForwardDiff.Tag{DiffEqBase.OrdinaryDiffEqTag, Float64}, Float64, _A}, 1} where _A}} where _A), DifferentiationInterfaceForwardDiffExt.ForwardDiffTwoArgJacobianPrep{Nothing, C, Tuple{}} where C<:(ForwardDiff.JacobianConfig{ForwardDiff.Tag{DiffEqBase.OrdinaryDiffEqTag, Float64}, Float64, _A, <:Tuple{Array{ForwardDiff.Dual{ForwardDiff.Tag{DiffEqBase.OrdinaryDiffEqTag, Float64}, Float64, _A}, 1} where _A, Array{ForwardDiff.Dual{ForwardDiff.Tag{DiffEqBase.OrdinaryDiffEqTag, Float64}, Float64, _A}, 1} where _A}} where _A)}))

Time series

fig = plot(title="MMP")
for (i, dox) in enumerate(doxrange)
    plot!(fig, sim[i], idxs=(sys.t/1000, sys.dpsi), lab="DOX = $(dox) μM")
end
plot!(fig, ylabel="mV", xlabel="Time (s)") |> PNG

fig = plot(title="ATP")
for (i, dox) in enumerate(doxrange)
    plot!(fig, sim[i], idxs=(sys.t/1000, sys.atp_i), lab="DOX = $(dox) μM")
end
plot!(fig, ylabel="Conc. (μM)", xlabel="Time (s)", legend=:bottomright, ylim=(0, 8mM)) |> PNG

fig = plot(title="Cytosolic superoxide")
for (i, dox) in enumerate(doxrange)
    plot!(fig, sim[i], idxs=(sys.t/1000, sys.sox_i), lab="DOX = $(dox) μM")
end
plot!(fig, ylabel="Conc. (μM)", xlabel="Time (s)", legend=:right) |> PNG

fig = plot(title="Mitochondrial superoxide")
for (i, dox) in enumerate(doxrange)
    plot!(fig, sim[i], idxs=(sys.t/1000, sys.sox_m), lab="DOX = $(dox) μM")
end
plot!(fig, ylabel="Conc. (μM)", xlabel="Time (s)", legend=:topright) |> PNG

fig = plot(title="Superoxide production")
for (i, dox) in enumerate(doxrange)
    plot!(fig, sim[i], idxs=(sys.t/1000, sys.vROS), lab="DOX = $(dox) μM")
end
plot!(fig, ylabel="Rate (μM/ms)", xlabel="Time (s)", legend=:right) |> PNG

fig = plot(title="O2 shunt")
for (i, dox) in enumerate(doxrange)
    plot!(fig, sim[i], idxs=(sys.t/1000, 100*sys.vROS / (sys.vO2 + sys.vROS)), lab="DOX = $(dox) μM")
end
plot!(fig, ylabel="Percentage (%)", xlabel="Time (s)", legend=:right) |> PNG

Q cycle

@unpack Q_n, SQn, QH2_n, QH2_p, Q_p, fes_ox, fes_rd, cytc_ox, cytc_rd = sys
plot(sim[end], idxs=[Q_n + Q_p, SQn, QH2_n+QH2_p], title="Q cycle ", legend=:right) |> PNG

plot(sim[end], idxs=[fes_ox, fes_rd, cytc_ox, cytc_rd], title="Q cycle (downstream)", legend=:right) |> PNG

@unpack cit, isoc, oaa, akg, scoa, suc, fum, mal, nadh_m = sys
plot(sim[end], idxs=[cit, isoc, oaa, akg, scoa, suc, fum, mal, nadh_m], title="TCA cycle ", legend=:right) |> PNG

This notebook was generated using Literate.jl.

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