public Tube Dilut(Tube T,double ratio)
{
for (int s=0;s<T.TP.NumberOfStrains;s++)
{
double NewN = Utils.RandBinomial(T.LastN[s],ratio);
T.GrowDivision[T.LastT,s]-=T.LastN[s] - NewN;
}
T.LastT++;
return T;
}
private static void RunOneSimulation(object o)
{
try
{
SimulationParameters PS = (SimulationParameters)o;
int rep = PS.rep;
int mi = PS.mi;
int sid = PS.sid;
double MutationRate = MutationRates[mi];
TubeParameters TP = new TubeParameters(Nmax,new StrainParameters[]{
new StrainParameters("WT",1e4,0,LagTS,1000,LagTS,1000,21,3,new StrainMutationParameters[]{new StrainMutationParameters(1,MutationRate,0)}),
new StrainParameters("ResistanceMutant",0,0,LagTS,1000,0,0,21,3)
});
Tube tube = new Tube(TP,maxTime);
SimulateTube SimulateTube = new SimulateTube(PS.sid);
tube = SimulateTube.GrowToNmax(tube);
int s;
for(s=0;s<maxsycles;s++)
{
tube = SimulateTube.Kill(tube,240);
tube = SimulateTube.GrowToNmax(tube);
//arize of mutant
if(tube.LastN[1]>0)
{
Cycle2Mutant[mi,rep]=s;
}
//test 4 fixsasion or extiction.
if(((double)tube.LastN[1]/(tube.LastN[0]+tube.LastN[1])>0.7) || double.IsNaN((double)tube.LastN[1]/(tube.LastN[0]+tube.LastN[1])))
{
break;
}
}
if(double.IsNaN((double)tube.LastN[1]/(tube.LastN[0]+tube.LastN[1])))
{
Cycle2Fixsation[mi,rep] = 0;
}
else
{
if(((double)tube.LastN[1]/(tube.LastN[0]+tube.LastN[1])>0.7))
{
Cycle2Fixsation[mi,rep] = s;
}
}
if(DebugPrint)
{
PrintTube2File("Lag=" + LagTS.ToString() + "Repetition=" + rep.ToString() + "MutationRate=" + MutationRate.ToString("e") ,tube);
}
SimulateTube = null;
PrintMutFix2File( simResultsFilename, mi, rep);
}
finally
{
//Console.WriteLine(numerOfThreadsNotYetCompleted);
PrintPresentege(MutationRates.Length*Repetitions-numerOfThreadsNotYetCompleted ,MutationRates.Length*Repetitions);
if (Interlocked.Decrement(ref numerOfThreadsNotYetCompleted) == 0)
{
_doneEvent.Set();
}
}
}
private static void PrintTube2File(string Filename,Tube T)
{
Filename+= ".txt";
System.IO.StreamWriter SR = new StreamWriter(Filename, false);
double[,] N = T.NBacteria;
double[] t = T.Time;
for (int i=0; i<N.GetLength(0); i++)
{
SR.Write("{0}\t",t[i]);
for (int j=0; j<N.GetLength(1); j++)
{
SR.Write("{0}\t",N[i,j]);
}
SR.WriteLine();
}
SR.Close();
}
public Tube GrowToNmax(Tube T)
{
double[] N = new double[T.TP.NumberOfStrains];
double NTot = 0;
CommuteLagForGrow(T);
for (int s=0;s<T.TP.NumberOfStrains;s++)
{
N[s]=T.LastN[s];
}
int t=T.LastT;
do
{
for (int s=0;s<T.TP.NumberOfStrains;s++)
{
double[] Mutants = new double[T.TP.NumberOfStrains];
double SumMutants =0 ;
//zero all mutans
for (int ms=0;ms<T.TP.NumberOfStrains;ms++)
{Mutants[ms] = 0;}
//calculate number of division results a mutation.
for(int ms=0;ms<T.TP.Strains[s].StrainMutationParameters.Length;ms++)
{
Mutants[T.TP.Strains[s].StrainMutationParameters[ms].Tostrain] = Utils.RandBinomial(T.GrowDivision[t,s],T.TP.Strains[s].StrainMutationParameters[ms].MutationRatePerDivition);
SumMutants+= Mutants[T.TP.Strains[s].StrainMutationParameters[ms].Tostrain] ;
}
//normal divisions
for(int i=0;i<T.GrowDivision[t,s]-SumMutants;i++)
{
//add the next 2 divisions
int ind;
ind = GetDivisionTimeIndex(T.TP.Strains[s].DivLognormalParameters,T.dt);
T.GrowDivision[t+ind,s]++;
ind = GetDivisionTimeIndex(T.TP.Strains[s].DivLognormalParameters,T.dt);
T.GrowDivision[t+ind,s]++;
N[s]++;
}
//mutation creating divitions.
for(int ms=0;ms<Mutants.Length;ms++)
{
for(int i=0;i<Mutants[ms];i++)
{
//add the next 2 divisions
int ind;
//normal cell
ind = GetDivisionTimeIndex(T.TP.Strains[s].DivLognormalParameters,T.dt);
T.GrowDivision[t+ind,s]++;
//Mutants cell
ind = GetDivisionTimeIndex(T.TP.Strains[s].DivLognormalParameters,T.dt);
T.GrowDivision[t+ind,ms]++;
N[ms]++;
}
}
}
t++;
NTot = 0;
for (int s=0;s<T.TP.NumberOfStrains;s++)
{
NTot += N[s];
}
}while (NTot<T.TP.Nmax && t<T.GrowDivision.GetLength(0));
T.LastT = t-1;
//zero future divitions
for(int tt = t; tt<T.GrowDivision.GetLength(0);tt++)
{
for (int s=0;s<T.TP.NumberOfStrains;s++)
{
T.GrowDivision[tt,s]=0;
}
}
return T;
}
private Tube CommuteLagForKill(Tube T)
{
return CommuteLag( T,-1);
}
private Tube CommuteLagForGrow(Tube T)
{
return CommuteLag( T, 1);
}
private Tube CommuteLag(Tube T,double GrowKill)
{
//Get LagTime for each bacteria strain
for(int s=0;s<T.TP.NumberOfStrains;s++)
{
//Calc Number of normal cels
double N0Persisters = Math.Round((double)T.LastN[s]*T.TP.Strains[s].PersistersLevel);
double N0Normal = T.LastN[s] - N0Persisters;
double mulagNormal;
double mulagPersisters;
if (GrowKill == 1)//grow
{
mulagNormal = 1.0/T.TP.Strains[s].LagMeanNormal;
mulagPersisters = 1.0/T.TP.Strains[s].LagMeanPersisters;
}
else//kill
{
mulagNormal = 1.0/T.TP.Strains[s].KillLagMeanNormal;
mulagPersisters = 1.0/T.TP.Strains[s].KillLagMeanPersisters;
}
if (mulagNormal!=double.PositiveInfinity)
{
//put normal first divition
for(int i=0;i<N0Normal;i++)
{
//Get the lag time
double LagTime = Utils.RandDecayExponantial(mulagNormal) ;
int GagEndInd = GetIndFromdouble(LagTime,T.dt);
//Get the divition (after the end of lag)
int Divind = GetDivisionTimeIndex(T.TP.Strains[s].DivLognormalParameters,T.dt);
T.GrowDivision[Divind+GagEndInd+T.LastT,s]+=GrowKill;
}
}
if (mulagPersisters!=double.PositiveInfinity)
{
//put Persisters first divition
for(int i=0;i<N0Persisters;i++)
{
//Get the lag time for persisters.
double LagTime = Utils.RandDecayExponantial(mulagPersisters);
int GagEndInd = GetIndFromdouble(LagTime,T.dt);
//Get the divition (after the end of lag)
int Divind = GetDivisionTimeIndex(T.TP.Strains[s].DivLognormalParameters,T.dt);
T.GrowDivision[Divind+GagEndInd+T.LastT,s]+=GrowKill;
}
}
}
return T;
}
public Tube Kill(Tube T,double KillTime)
{
//usin kill whan bacteria divides
CommuteLagForKill(T);
int KillTimeInIndexs = (int)Math.Round(KillTime/T.dt) ;
//zero future divitions
for(int tt = T.LastT + KillTimeInIndexs; tt<T.GrowDivision.GetLength(0);tt++)
{
for (int s=0;s<T.TP.NumberOfStrains;s++)
{
T.GrowDivision[tt,s]=0;
}
}
T.LastT += KillTimeInIndexs;
return T;
}
public Tube GrowToTime(Tube T,double Time)
{
int GrowTimeInIndexs = (int)Math.Round(Time/T.dt) ;
int EndGrowingIndex = GrowTimeInIndexs + T.LastT;
double[] N = new double[T.TP.NumberOfStrains];
double NTot = 0;
CommuteLagForGrow(T);
for (int s=0;s<T.TP.NumberOfStrains;s++)
{
N[s]=T.LastN[s];
}
int t=T.LastT;
do
{
NTot = 0;
for (int s=0;s<T.TP.NumberOfStrains;s++)
{
for(int i=0;i<T.GrowDivision[t,s];i++)
{
//add the next 2 divisions
int ind;
ind = GetDivisionTimeIndex(T.TP.Strains[s].DivLognormalParameters,T.dt);
T.GrowDivision[t+ind,s]++;
ind = GetDivisionTimeIndex(T.TP.Strains[s].DivLognormalParameters,T.dt);
T.GrowDivision[t+ind,s]++;
N[s]++;
}
NTot +=N[s];
}
t++;
}while (t<EndGrowingIndex);
T.LastT = t-1;
//zero future divitions
for(int tt = t; tt<T.GrowDivision.GetLength(0);tt++)
{
for (int s=0;s<T.TP.NumberOfStrains;s++)
{
T.GrowDivision[tt,s]=0;
}
}
return T;
}
