Alarcon2004OxygenBasedCellCycleOdeSystem.cpp

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*/

#include "Alarcon2004OxygenBasedCellCycleOdeSystem.hpp"
#include "CellwiseOdeSystemInformation.hpp"

Alarcon2004OxygenBasedCellCycleOdeSystem::Alarcon2004OxygenBasedCellCycleOdeSystem(double oxygenConcentration,
                                                                                   bool isLabelled,
                                                                                   std::vector<double> stateVariables)
    : AbstractOdeSystem(6),
      mOxygenConcentration(oxygenConcentration),
      mIsLabelled(isLabelled)
{
    mpSystemInfo.reset(new CellwiseOdeSystemInformation<Alarcon2004OxygenBasedCellCycleOdeSystem>);

    Init(); // set up parameters

    // Parameter values are taken from the Alarcon et al. (2004) paper
    if (mIsLabelled) // labelled "cancer" cells
    {
        ma1 = 0.04;
        mc1 = 0.007;
        mxThreshold = 0.004;
        myThreshold = 0.05;
    }
    else // normal cells
    {
        ma1 = 0.05;
        mc1 = 0.1;
        mxThreshold = 0.004;
        myThreshold = 0.2;
    }

    // Cell-specific initial conditions
    SetDefaultInitialCondition(3, 0.5*mMstar);
    SetDefaultInitialCondition(5, oxygenConcentration);

    if (stateVariables != std::vector<double>())
    {
        SetStateVariables(stateVariables);
    }
}

Alarcon2004OxygenBasedCellCycleOdeSystem::~Alarcon2004OxygenBasedCellCycleOdeSystem()
{
    // Do nothing
}

void Alarcon2004OxygenBasedCellCycleOdeSystem::Init()
{
    // Parameter values are taken from the Alarcon et al. (2004) paper
    ma2 = 1.0;
    ma3 = 0.25;
    ma4 = 0.04;
    mb3 = 10.0;
    mb4 = 5.5;
    mc2 = 0.01;
    md1 = 0.01;
    md2 = 0.1;
    mJ3 = 0.04;
    mJ4 = 0.04;
    mEta = 0.01;
    mMstar = 10.0;
    mB = 0.01;
}

void Alarcon2004OxygenBasedCellCycleOdeSystem::EvaluateYDerivatives(double time, const std::vector<double>& rY, std::vector<double>& rDY)
{
    double x = rY[0];
    double y = rY[1];
    double z = rY[2];
    double mass = rY[3];
    double u = rY[4];
    double oxygen_concentration = rY[5];

    double dx = 0.0;
    double dy = 0.0;
    double dz = 0.0;
    double dmass = 0.0;
    double du = 0.0;

    /*
     % The variables are
     % 1. x = Cdh1-APC complexes
     % 2. y = cyclin-CDK
     % 3. z = p27
     % 4. m = mass
     % 5. u = RBNP
    */

    dx = ((1 + mb3*u)*(1-x))/(mJ3 + 1 - x) - (mb4*mass*x*y)/(mJ4 + x);
    dy = ma4 -(ma1 + ma2*x + ma3*z)*y;

    // Parameter values are taken from the Alarcon et al. (2004) paper
    if (mIsLabelled) // labelled "cancer" cells
    {
        dz = mc1 - mc2*oxygen_concentration*z/(mB + oxygen_concentration);
    }
    else // normal cells
    {
        dz = mc1*(1 - mass/mMstar) - mc2*oxygen_concentration*z/(mB + oxygen_concentration);
    }

    dmass = mEta*mass*(1 - mass/mMstar);
    du = md1 - (md2 + md1*y)*u;

    // Rescale time to be in hours
    rDY[0] = 60.0*dx;
    rDY[1] = 60.0*dy;
    rDY[2] = 60.0*dz;
    rDY[3] = 60.0*dmass;
    rDY[4] = 60.0*du;
    rDY[5] = 0.0; // do not change the oxygen concentration
}

bool Alarcon2004OxygenBasedCellCycleOdeSystem::CalculateStoppingEvent(double time, const std::vector<double>& rY)
{
    return (rY[0] < mxThreshold && rY[1] > myThreshold);
}

template<>
void CellwiseOdeSystemInformation<Alarcon2004OxygenBasedCellCycleOdeSystem>::Initialise()
{
    this->mVariableNames.push_back("Cdh1_APC_complexes");
    this->mVariableUnits.push_back("non_dim");
    this->mInitialConditions.push_back(0.9);

    this->mVariableNames.push_back("cyclin_CDK");
    this->mVariableUnits.push_back("non_dim");
    this->mInitialConditions.push_back(0.01);

    this->mVariableNames.push_back("p27");
    this->mVariableUnits.push_back("non_dim");
    this->mInitialConditions.push_back(0.0);

    this->mVariableNames.push_back("mass");
    this->mVariableUnits.push_back("non_dim");
    this->mInitialConditions.push_back(NAN); // will be filled in later

    this->mVariableNames.push_back("RBNP");
    this->mVariableUnits.push_back("non_dim");
    this->mInitialConditions.push_back(1.0);

    this->mVariableNames.push_back("O2");
    this->mVariableUnits.push_back("non_dim");
    this->mInitialConditions.push_back(NAN); // will be filled in later

    this->mInitialised = true;
}

void Alarcon2004OxygenBasedCellCycleOdeSystem::SetIsLabelled(bool isLabelled)
{
    mIsLabelled = isLabelled;
}

bool Alarcon2004OxygenBasedCellCycleOdeSystem::IsLabelled() const
{
    return mIsLabelled;
}

double Alarcon2004OxygenBasedCellCycleOdeSystem::GetOxygenConcentration() const
{
    return mOxygenConcentration;
}

// Serialization for Boost >= 1.36
#include "SerializationExportWrapperForCpp.hpp"
CHASTE_CLASS_EXPORT(Alarcon2004OxygenBasedCellCycleOdeSystem)