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itkBioCellBase.cxx
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itkBioCellBase.cxx
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/*=========================================================================
Program: Insight Segmentation & Registration Toolkit
Module: itkBioCellBase.cxx
Language: C++
Date: $Date$
Version: $Revision$
Copyright (c) 2002 Insight Consortium. All rights reserved.
See ITKCopyright.txt or http://www.itk.org/HTML/Copyright.htm for details.
This software is distributed WITHOUT ANY WARRANTY; without even
the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR
PURPOSE. See the above copyright notices for more information.
=========================================================================*/
#include "itkBioCellBase.h"
#include <new>
#include "vnl/vnl_math.h"
#include "vnl/vnl_sample.h"
namespace itk {
namespace bio {
CellBase::ColorType CellBase::DefaultColor;
double CellBase::DefaultRadius = 1.00; // microns
double CellBase::GrowthRadiusIncrement = 0.01; // microns
double CellBase::GrowthRadiusLimit = 2.00; // microns
unsigned long CellBase::MaximumGenerationLimit = 30L; // 30th generation
unsigned long CellBase::GrowthMaximumLatencyTime = 50;
unsigned long CellBase::DivisionMaximumLatencyTime = 50;
double CellBase::NutrientSelfRepairLevel = 0;
double CellBase::EnergySelfRepairLevel = 0;
double CellBase::DefaultEnergyIntake = 1;
double CellBase::DefaultNutrientsIntake = 1;
unsigned long CellBase::Counter = 0; // number of cells created
CellBase::GeneIdType CellBase::RedGene = "Red";
CellBase::GeneIdType CellBase::GreenGene = "Green";
CellBase::GeneIdType CellBase::BlueGene = "Blue";
CellBase::GeneIdType CellBase::Cdk2E = "Cdk2E";
CellBase::GeneIdType CellBase::Caspase = "Caspase";
CellBase::GeneIdType CellBase::Pressurin = "Pressurin";
double CellBase::ChemoAttractantLowThreshold = 200.0f;
double CellBase::ChemoAttractantHighThreshold = 255.0f;
CellBase::ColorType CellBase::WellNourishedColor;
CellBase::ColorType CellBase::HopefullColor;
CellBase::ColorType CellBase::StarvingColor;
/**
* Constructor Lonely Cell
*/
CellBase
::CellBase()
{
m_Genome = NULL;
m_GenomeCopy = NULL;
m_Radius = DefaultRadius;
m_Color = DefaultColor;
m_Pressure = 0.0f;
m_ParentIdentifier = 0; // Parent cell has to write here
// The first Cell is numbered as 1
Counter++;
m_SelfIdentifier = Counter;
m_Generation = 0;
m_CycleState = Gap1; // cells are created in Gap1 state
// Start with minimum reserves
m_NutrientsReserveLevel = NutrientSelfRepairLevel + DefaultNutrientsIntake;
m_EnergyReserveLevel = EnergySelfRepairLevel + DefaultEnergyIntake;
// delay before starting to grow after Mitosis
m_GrowthLatencyTime = static_cast<unsigned long>(
vnl_sample_uniform( 0UL, this->GetGrowthMaximumLatencyTime()) );
// add a random time before starting to grow
m_DivisionLatencyTime = static_cast<unsigned long>(
vnl_sample_uniform( 0, this->GetDivisionMaximumLatencyTime() ) );
m_ScheduleApoptosis = false;
m_ChemoAttractantLevel = 200.0f;
// too young to die...
m_MarkedForRemoval = false;
}
/**
* Destructor
*/
CellBase
::~CellBase()
{
if( m_Genome )
{
delete m_Genome;
m_Genome = NULL;
}
if( m_GenomeCopy )
{
delete m_GenomeCopy;
m_GenomeCopy = NULL;
}
}
/**
* DNA Replication
*/
void
CellBase
::DNAReplication(void)
{
m_GenomeCopy = new GenomeType;
m_GenomeCopy->Copy( *m_Genome );
}
/**
* Programmed Cell Death
* This is the cellular equivalent of suicide.
*/
void
CellBase
::Apoptosis(void)
{
if( m_Genome )
{
delete m_Genome;
m_Genome = NULL;
}
if( m_GenomeCopy )
{
delete m_GenomeCopy;
m_GenomeCopy = NULL;
}
}
/**
* Check point after division
* This check point will control
* the entrance in the growth stage.
* It returns true when conditions
* required for growth are satisfied.
*/
bool
CellBase
::CheckPointGrowth(void)
{
return true;
}
/**
* Check point before initiating DNA replication.
* This check point controls the entrance in the
* duplication of the genome by DNA synthesis, also
* known as the S phase of the Cell cycle.
* This method returns true when conditions required
* for DNA replication are satisfied.
*/
bool
CellBase
::CheckPointDNAReplication(void)
{
// radius & teleomerasa counting should be removed from here
// and be related to Cdk expression by using proteins like P53
// The radius should be estimated by a cytoskeleton-related protein.
const bool fatality = (m_Generation < MaximumGenerationLimit );
const bool radius = (m_Radius >= GrowthRadiusLimit);
bool isOkToReplicate = true;
const double cdk2E = m_Genome->GetExpressionLevel( Cdk2E );
if( cdk2E < 0.8 )
{
isOkToReplicate = false;
}
bool tooEarlyToReplicate = true;
if( m_DivisionLatencyTime )
{
m_DivisionLatencyTime--;
}
else
{
tooEarlyToReplicate = false;
}
bool goodCellMatrix = false;
if( !m_ScheduleApoptosis )
{
if( m_ChemoAttractantLevel > ChemoAttractantLowThreshold &&
m_ChemoAttractantLevel < ChemoAttractantHighThreshold )
{
goodCellMatrix = true;
}
}
return ( radius && fatality && isOkToReplicate &&
!tooEarlyToReplicate && goodCellMatrix);
}
/**
* Check point before dividing the cell in two daughter cells
* at this point DNA replication has already been performed
* as well as DNA proofreading and error corrections. This
* check point in principle shoult test if the resulting
* genomes satisfy the quality standards of a living cell.
*/
bool
CellBase
::CheckPointMitosis(void)
{
const bool DNAProofRead = ( m_GenomeCopy && m_Genome );
if( !DNAProofRead )
{
std::cerr << "PANIC: DNA failed ! " << std::endl;
}
return DNAProofRead;
}
/**
* Check point before apoptosis
* This check point will control
* the entrance in the apoptosis stage.
* It returns true when conditions
* required for apoptosis are satisfied.
* The cell will die in apoptosis.
*/
bool
CellBase
::CheckPointApoptosis(void)
{
bool executeApoptosis;
if( m_Genome->GetExpressionLevel( Caspase ) > 0.8 )
{
executeApoptosis = true;
}
else
{
executeApoptosis = false;
}
return executeApoptosis;
}
/**
* Initialize common variables
* All this should go away once we setup Gene Networks for controlling the cell.
*/
void
CellBase
::Initialize(void)
{
CellBase::SetGrowthMaximumLatencyTime( 100 );
CellBase::SetDivisionMaximumLatencyTime( 100 );
CellBase::GrowthRadiusIncrement = 0.01;
CellBase::GrowthRadiusLimit = 2.00;
SetMaximumGenerationLimit( 40 ); // it should use Teleomeres for implementing this
WellNourishedColor.Set( 0.0, 0.0, 1.0 );
HopefullColor.Set( 0.0, 1.0, 0.0 );
StarvingColor.Set( 1.0, 0.0, 0.0 );
SetDefaultColor( HopefullColor );
}
/**
* Mark this cell for removal
* The cellular aggregate with remove
* this cell from its list at the earliest occasion
*/
void
CellBase
::MarkForRemoval(void)
{
m_MarkedForRemoval = true;
}
/**
* Mark this cell for removal
* The cellular aggregate with remove
* this cell from its list at the earliest occasion
*/
bool
CellBase
::MarkedForRemoval(void) const
{
return m_MarkedForRemoval;
}
/**
* Cell Growth
* Growth is conditioned to the availability of
* nutrients and energy beyond the critical limit
* of self-repair
*
* Growth is limited by a constraint in the size
* of cell's radius
*/
void
CellBase
::Grow(void)
{
if( m_GrowthLatencyTime )
{
m_GrowthLatencyTime--;
return;
}
if ( m_NutrientsReserveLevel > NutrientSelfRepairLevel &&
m_EnergyReserveLevel > EnergySelfRepairLevel )
{
m_Radius += GrowthRadiusIncrement;
if( m_Radius > GrowthRadiusLimit )
{
m_Radius = GrowthRadiusLimit;
}
}
}
/**
* Set Growth Latency Time
*/
void
CellBase
::SetGrowthMaximumLatencyTime( unsigned long latency )
{
CellBase::GrowthMaximumLatencyTime = latency;
}
/**
* Get Growth Latency Time
*/
unsigned long
CellBase
::GetGrowthMaximumLatencyTime( void )
{
return CellBase::GrowthMaximumLatencyTime;
}
/**
* Return the ID of this cell
*/
CellBase::IdentifierType
CellBase
::GetSelfIdentifier(void) const
{
return m_SelfIdentifier;
}
/**
* Return the ID of the parent cell
*/
CellBase::IdentifierType
CellBase
::GetParentIdentifier(void) const
{
return m_ParentIdentifier;
}
/**
* Return the radius
*/
double
CellBase
::GetRadius(void) const
{
return m_Radius;
}
/**
* Return the Color
*/
CellBase::ColorType
CellBase
::GetColor(void) const
{
return m_Color;
}
/**
* Set the value of the limiting cell radius
* this is a static value used for the whole
* cellular aggregate
*/
void
CellBase
::SetGrowthRadiusLimit( double value )
{
GrowthRadiusLimit = value;
}
/**
* Set the amount of Energy that is needed for Self-repair.
* Cells that go below this level will degrade and enter
* termination stage.
*/
void
CellBase
::SetEnergySelfRepairLevel( double value )
{
EnergySelfRepairLevel = value;
}
/**
* Set the amount of Nutrients that are needed for Self-repair.
* Cells that go below this level will degrade and enter
* termination stage.
*/
void
CellBase
::SetNutrientSelfRepairLevel( double value )
{
NutrientSelfRepairLevel = value;
}
/**
* Set the value of the limit of cell generation.
* After this generation cells will stop dividing
* A mechanism similar to the inhibition of Telomerase
* that impose a limit to the maximum number of times
* that the genome can be replicated.
*/
void
CellBase
::SetMaximumGenerationLimit( unsigned long generationLimit )
{
MaximumGenerationLimit = generationLimit;
}
/**
* Get the value of the limiting cell radius
* this is a static value used for the whole
* cellular aggregate
*/
double
CellBase
::GetGrowthRadiusLimit( void )
{
return GrowthRadiusLimit;
}
/**
* Set the value of the increment in cellular
* radius at each time step
* this is a static value used for the whole
* cellular aggregate
*/
void
CellBase
::SetGrowthRadiusIncrement( double value )
{
GrowthRadiusIncrement = value;
}
/**
* Ingestion of nutrients
*/
void
CellBase
::NutrientsIntake(void)
{
m_NutrientsReserveLevel += DefaultNutrientsIntake;
}
/**
* Acquisition of energy
*/
void
CellBase
::EnergyIntake(void)
{
m_EnergyReserveLevel += DefaultEnergyIntake;
}
/**
* Compute the Gene Network
* This method update the level of expression of
* all the genes in the cell's genome.
* see: http://www.ingeneue.org for details
*/
void
CellBase
::ComputeGeneNetwork(void)
{
// Default level of pigments
m_Genome->SetExpressionLevel( CellBase::RedGene, 1.0 );
m_Genome->SetExpressionLevel( CellBase::GreenGene, 1.0 );
m_Genome->SetExpressionLevel( CellBase::BlueGene, 1.0 );
// Color the cell acording to pressure.
// This is done by generating pigments under
// the influence of presure.
const double pressurinLevel = m_Genome->GetExpressionLevel( Pressurin );
const double red = GenomeType::Sigmoide( 5.0, 1.0, pressurinLevel );
m_Genome->SetExpressionLevel( RedGene, red );
m_Genome->SetExpressionLevel( BlueGene, 1.0-red );
m_Genome->SetExpressionLevel( GreenGene, 0.0 );
// Color the Cell acording to the substrate.
// This is done by generating pigments.
// This color overrides the selection of the Presure...
if( m_ChemoAttractantLevel > ChemoAttractantHighThreshold )
{
m_Genome->SetExpressionLevel( RedGene, WellNourishedColor.GetRed() );
m_Genome->SetExpressionLevel( GreenGene, WellNourishedColor.GetGreen() );
m_Genome->SetExpressionLevel( BlueGene, WellNourishedColor.GetBlue() );
}
else if( m_ChemoAttractantLevel > ChemoAttractantLowThreshold )
{
m_Genome->SetExpressionLevel( RedGene, HopefullColor.GetRed() );
m_Genome->SetExpressionLevel( GreenGene, HopefullColor.GetGreen() );
m_Genome->SetExpressionLevel( BlueGene, HopefullColor.GetBlue() );
}
else
{
m_Genome->SetExpressionLevel( RedGene, StarvingColor.GetRed() );
m_Genome->SetExpressionLevel( GreenGene, StarvingColor.GetGreen() );
m_Genome->SetExpressionLevel( BlueGene, StarvingColor.GetBlue() );
}
// Prevent cells from replicating if they are in a high pressure zone
const double cdk2E = GenomeType::Sigmoide( 2.0, -0.5, pressurinLevel );
m_Genome->SetExpressionLevel( Cdk2E, cdk2E );
// If the pressure is really high, then commit suicide
const double caspase = GenomeType::Sigmoide( 3.0, 90.0, pressurinLevel );
m_Genome->SetExpressionLevel( Caspase, caspase );
}
/**
* Secrete synthetized products resulting from
* the gene network update
*/
void
CellBase
::SecreteProducts(void)
{
m_Color.SetRed( m_Genome->GetExpressionLevel( RedGene ) );
m_Color.SetGreen( m_Genome->GetExpressionLevel( GreenGene ) );
m_Color.SetBlue( m_Genome->GetExpressionLevel( BlueGene ) );
}
/**
* Set default Color
*/
void
CellBase
::SetDefaultColor( const ColorType & color )
{
DefaultColor = color;
}
/**
* Reset the counter
*/
void
CellBase
::ResetCounter( void )
{
Counter = 0;
}
/**
* Set Division Latency Time
*/
void
CellBase
::SetDivisionMaximumLatencyTime( unsigned long latency )
{
CellBase::DivisionMaximumLatencyTime = latency;
}
/**
* Get Division Latency Time
*/
unsigned long
CellBase
::GetDivisionMaximumLatencyTime( void )
{
return CellBase::DivisionMaximumLatencyTime;
}
/**
* Set ChemoAttractantLowThreshold
*/
void
CellBase
::SetChemoAttractantLowThreshold( double lowvalue )
{
CellBase::ChemoAttractantLowThreshold = lowvalue;
}
/**
* Set ChemoAttractantHighThreshold
*/
void
CellBase
::SetChemoAttractantHighThreshold( double highvalue )
{
CellBase::ChemoAttractantHighThreshold = highvalue;
}
} // end namespace bio
} // end namespace itk