Owen2011OxygenBasedCellCycleOdeSystem.cpp

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 */

#include "Owen2011OxygenBasedCellCycleOdeSystem.hpp"
#include "CellwiseOdeSystemInformation.hpp"
#include "CancerCellMutationState.hpp"
#include "QuiescentCancerCellMutationState.hpp"
#include "WildTypeCellMutationState.hpp"
#include "TipCellMutationState.hpp"
#include "StalkCellMutationState.hpp"
#include "Owen11Parameters.hpp"
#include "Secomb04Parameters.hpp"
#include "GenericParameters.hpp"
#include "BaseUnits.hpp"

Owen2011OxygenBasedCellCycleOdeSystem::Owen2011OxygenBasedCellCycleOdeSystem(units::quantity<unit::concentration> oxygenConcentration,
        boost::shared_ptr<AbstractCellMutationState> mutation_state,
        std::vector<double> stateVariables)
: AbstractOdeSystem(4),
  mOxygenConcentration(oxygenConcentration),
  pmMutationState(mutation_state),
  mReferenceTimeScale(BaseUnits::Instance()->GetReferenceTimeScale()),
  mReferenceConcentrationScale(BaseUnits::Instance()->GetReferenceConcentrationScale())
{
    mpSystemInfo.reset(new CellwiseOdeSystemInformation<Owen2011OxygenBasedCellCycleOdeSystem>);
    mpSystemInfo->SetDefaultInitialCondition(3, mOxygenConcentration/mReferenceConcentrationScale);

    mk7 = Owen11Parameters::mpP53ProductionRateConstant->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
    mk7dash = Owen11Parameters::mpP53MaxDegradationRate->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
    mCp53 = Owen11Parameters::mpOxygenTensionForHalfMaxP53Degradation->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
    mk8 = Owen11Parameters::mpCellVegfProductionRate->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
    mJ5 = Owen11Parameters::mpVegfEffectOnVegfProduction->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
    mk8dash = Owen11Parameters::mpMaxCellVegfProductionRate->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
    mCVEGF = Owen11Parameters::mpOxygenTensionForHalfMaxVegfDegradation->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");

    // Parameter values are taken from the Owen (2011) paper
    if (pmMutationState->IsType<CancerCellMutationState>() || pmMutationState->IsType<QuiescentCancerCellMutationState>()) // cancer cell
    {
        mCphi = Owen11Parameters::mpOxygenPartialPressureAtHalfMaxCycleRateCancer->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
        mTmin = Owen11Parameters::mpMinimumCellCyclePeriodCancer->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
        mk8doubledash = Owen11Parameters::mpP53EffectOnVegfProduction->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
    }
    else // all other cells
    {
        mCphi = Owen11Parameters::mpOxygenPartialPressureAtHalfMaxCycleRateNormal->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
        mTmin = Owen11Parameters::mpMinimumCellCyclePeriodNormal->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
        mk8doubledash = Owen11Parameters::mpP53EffectOnVegfProduction->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");
    }

    mReferenceSolubility =
            Secomb04Parameters::mpOxygenVolumetricSolubility->GetValue("Owen2011OxygenBasedCellCycleOdeSystem") *
            GenericParameters::mpGasConcentrationAtStp->GetValue("Owen2011OxygenBasedCellCycleOdeSystem");

    /*
     % The variables are
     % 0. phi = Cell-cycle phase
     % 1. p53 = p53 concentration
     % 2. VEGF = VEGF concentration
     % 3. O2 = Oxygen concentration
     */
    if (stateVariables != std::vector<double>())
    {
        SetStateVariables(stateVariables);
    }
}

Owen2011OxygenBasedCellCycleOdeSystem::~Owen2011OxygenBasedCellCycleOdeSystem()
{

}

bool Owen2011OxygenBasedCellCycleOdeSystem::CalculateStoppingEvent(double time, const std::vector<double>& rY)
{
    return (rY[0] > 1);
}

void Owen2011OxygenBasedCellCycleOdeSystem::EvaluateYDerivatives(double time,
                                                                 const std::vector<double>& rY,
                                                                 std::vector<double>& rDY)
{
    /*
     % The variables are
     % 0. phi = Cell-cycle phase
     % 1. p53 = p53 concentration
     % 2. VEGF = VEGF concentration
     % 3. O2 = Oxygen concentration
     */
    double p53 = rY[1];
    double VEGF = rY[2];
    mOxygenConcentration = rY[3]*mReferenceConcentrationScale;

    units::quantity<unit::rate> dphi = 0.0* (1.0/ unit::seconds);
    units::quantity<unit::rate> dp53 = 0.0* (1.0/ unit::seconds);
    units::quantity<unit::rate> dVEGF = 0.0* (1.0/ unit::seconds);
    if (pmMutationState->IsType<CancerCellMutationState>() || pmMutationState->IsType<WildTypeCellMutationState>())
    {
        dphi = mOxygenConcentration/(mTmin*(mCphi*mReferenceSolubility + mOxygenConcentration));
    }
    else
    {
        dphi = 0.0 * (1.0/ unit::seconds);
    }

    dp53 = mk7 - mk7dash*p53*mOxygenConcentration/(mCp53*mReferenceSolubility + mOxygenConcentration);
    dVEGF = mk8 + mk8doubledash*p53*VEGF/(mJ5 + VEGF) - mk8dash*VEGF*mOxygenConcentration/(mCVEGF*mReferenceSolubility + mOxygenConcentration);

    // Non-dimensionalise wrt to the reference time scale
    rDY[0] = dphi*mReferenceTimeScale;
    rDY[1] = dp53*mReferenceTimeScale;
    rDY[2] = dVEGF*mReferenceTimeScale;
    rDY[3] = 0.0;
}

boost::shared_ptr<AbstractCellMutationState> Owen2011OxygenBasedCellCycleOdeSystem::GetMutationState() const
{
    return pmMutationState;
}

units::quantity<unit::concentration> Owen2011OxygenBasedCellCycleOdeSystem::GetOxygenConcentration() const
{
    return mOxygenConcentration;
}

template<>
void CellwiseOdeSystemInformation<Owen2011OxygenBasedCellCycleOdeSystem>::Initialise()
{
    this->mVariableNames.push_back("Cell_cycle_phase");
    this->mVariableUnits.push_back("unitless");
    this->mInitialConditions.push_back(0.0);
    this->mVariableNames.push_back("p53");
    this->mVariableUnits.push_back("unitless");
    this->mInitialConditions.push_back(0.0);
    this->mVariableNames.push_back("VEGF");
    this->mVariableUnits.push_back("unitless");
    this->mInitialConditions.push_back(0.0);
    this->mVariableNames.push_back("Oxygen");
    this->mVariableUnits.push_back("moles m^-3");
    this->mInitialConditions.push_back(0.0);
    this->mInitialised = true;
}

void Owen2011OxygenBasedCellCycleOdeSystem::SetMutationState(boost::shared_ptr<AbstractCellMutationState> pMutationState)
{
    pmMutationState = pMutationState;
}

// Serialization for Boost >= 1.36
#include "SerializationExportWrapperForCpp.hpp"
CHASTE_CLASS_EXPORT(Owen2011OxygenBasedCellCycleOdeSystem)