// Created by libAntimony v2.13.0
function effector_exhaustion_0(d1, E, R, f)
  d1*E*R*R*R*f;
end

effector_exhaustion_0 is "effector exhaustion"

function tumor_death_0(la, R)
  la*R/3;
end

tumor_death_0 is "tumor death"

function stimulation(r, R, E, k)
  r*R*R*R*E/(k + R*R*R);
end

stimulation is "stimulation"

function killing(c, E, R, f)
  c*E*R*f;
end

killing is "killing"

function tumor_growth_0(lm, B, R)
  lm*B*R/3;
end

tumor_growth_0 is "tumor growth"

function Constant_flux__irreversible(v)
  v;
end

Constant_flux__irreversible is "Constant flux (irreversible)"

function nutrience(lm, B, ld, R)
  lm*(1 - B)*ld/tanh(R/ld);
end

nutrience is "nutrience+"

function nutrience_0(lm, b, ld, R)
  lm*(1 - b)*ld*ld/R;
end

nutrience_0 is "nutrience-"


model *Reppas2015___tumor_control_via_alternating_immunostimulating_and_immunosuppressive_phases()

  // Compartments and Species:
  compartment tumor_microenvironment;
  species E in tumor_microenvironment, R in tumor_microenvironment, $f in tumor_microenvironment;
  species $E_0 in tumor_microenvironment;

  // Assignment Rules:
  f := R^(B - 1)/(R^(B - 1) + 1);
  E_0 := E/100000;

  // Reactions:
  tumor_growth:  => R; tumor_microenvironment*tumor_growth_0(lm, B, R);
  tumor_death: R => ; tumor_microenvironment*tumor_death_0(la, R);
  tumor_killing: R => ; tumor_microenvironment*killing(c, E_0, R, f);
  tumor_nutrient_supply:  => R; tumor_microenvironment*nutrience(lm, B, ld, R);
  effector_stimulation:  => E; tumor_microenvironment*stimulation(r, R, E, k);
  effector_exhaustion: E => ; tumor_microenvironment*effector_exhaustion_0(d1, E, R, f);
  effector_death: E => ; tumor_microenvironment*d0*E;
  effector_source:  => E; tumor_microenvironment*Constant_flux__irreversible(sigma);
  tumor_nutrient_missuply: R => ; tumor_microenvironment*nutrience_0(lm, B, ld, R);

  // Species initializations:
  E = 1000000;
  E has substance_per_volume;
  R = 2;
  R has substance_per_volume;
  f has substance_per_volume;
  E_0 has substance_per_volume;

  // Compartment initializations:
  tumor_microenvironment = 1;
  tumor_microenvironment has volume;

  // Variable initializations:
  B = 0.5;
  B has unit_0;
  lm = 1.34;
  lm has unit_1;
  la = 0.14;
  la has unit_1;
  ld = 0.3;
  ld has unit_0;
  c = 0.03;
  c has unit_1;
  k = 2.72;
  k has unit_0;
  d1 = 0.01;
  d1 has unit_1;
  d0 = 0.37;
  d0 has unit_1;
  sigma = 13000;
  sigma has unit_1;
  r = 0.57;
  r has unit_1;

  // Other declarations:
  const tumor_microenvironment, B, lm, la, ld, c, k, d1, d0, sigma, r;

  // Unit definitions:
  unit length = metre;
  unit area = metre^2;
  unit volume = 1e-3 litre;
  unit time_unit = time_unit;
  unit substance = 1e-3 mole;
  unit unit_0 = 1 / dimensionless^-0;
  unit unit_1 = 1 / 86400e-1 second;
  unit extent = substance;
  unit substance_per_volume = 1e-3 mole / 1e-3 litre;

  // Display Names:
  time_unit is "time";
  unit_0 is "1";
  unit_1 is "1/d";
  tumor_microenvironment is "tumor microenvironment";
  E_0 is "E'";
  tumor_growth is "tumor growth";
  tumor_death is "tumor death";
  tumor_killing is "tumor killing";
  tumor_nutrient_supply is "tumor nutrient supply";
  effector_stimulation is "effector stimulation";
  effector_exhaustion is "effector exhaustion";
  effector_death is "effector death";
  effector_source is "effector source";
  tumor_nutrient_missuply is "tumor nutrient missuply";

  // CV terms:
  tumor_microenvironment hypernym "http://identifiers.org/ncit/C94498"
  E hypernym "http://identifiers.org/ncit/C28241"
  R hypernym "http://identifiers.org/cl/CL:0001064"
  f hypernym "http://identifiers.org/ncit/C54025"
  E_0 hypernym "http://identifiers.org/ncit/C28241"
  lm hypernym "http://identifiers.org/sbo/SBO:0000610"
  la hypernym "http://identifiers.org/ncit/C53346"
  ld hypernym "http://identifiers.org/sbo/SBO:0000466"
  c hypernym "http://identifiers.org/ncit/C53346"
  k hypernym "http://identifiers.org/sbo/SBO:0000193"
  d1 hypernym "http://identifiers.org/ncit/C53346"
  d0 hypernym "http://identifiers.org/ncit/C53346"
  sigma hypernym "http://identifiers.org/sbo/SBO:0000610"
  r hypernym "http://identifiers.org/sbo/SBO:0000610"
  tumor_growth hypernym "http://identifiers.org/go/GO:0008283"
  tumor_growth hypernym "http://identifiers.org/sbo/SBO:0000393"
  tumor_death hypernym "http://identifiers.org/sbo/SBO:0000179"
  tumor_death hypernym "http://identifiers.org/go/GO:0008219"
  tumor_killing hypernym "http://identifiers.org/sbo/SBO:0000179"
  tumor_killing hypernym "http://identifiers.org/go/GO:0001909"
  tumor_nutrient_supply hypernym "http://identifiers.org/go/GO:0008283"
  tumor_nutrient_supply hypernym "http://identifiers.org/sbo/SBO:0000393"
  effector_stimulation hypernym "http://identifiers.org/sbo/SBO:0000393"
  effector_stimulation hypernym "http://identifiers.org/go/GO:0070661"
  effector_exhaustion hypernym "http://identifiers.org/go/GO:0008219"
  effector_exhaustion hypernym "http://identifiers.org/sbo/SBO:0000179"
  effector_death hypernym "http://identifiers.org/go/GO:0008219"
  effector_death hypernym "http://identifiers.org/sbo/SBO:0000179"
  effector_source hypernym "http://identifiers.org/sbo/SBO:0000393"
  effector_source hypernym "http://identifiers.org/go/GO:0070661"
  tumor_nutrient_missuply hypernym "http://identifiers.org/sbo/SBO:0000179"
  tumor_nutrient_missuply hypernym "http://identifiers.org/go/GO:0008219"
end

Reppas2015___tumor_control_via_alternating_immunostimulating_and_immunosuppressive_phases is "Reppas2015 - tumor control via alternating immunostimulating and immunosuppressive phases"

Reppas2015___tumor_control_via_alternating_immunostimulating_and_immunosuppressive_phases description "http://identifiers.org/pubmed/26305801"
Reppas2015___tumor_control_via_alternating_immunostimulating_and_immunosuppressive_phases model_entity_is "http://identifiers.org/biomodels.db/MODEL1907110002",
                                                                                                          "http://identifiers.org/biomodels.db/BIOMD0000000749"
Reppas2015___tumor_control_via_alternating_immunostimulating_and_immunosuppressive_phases hypernym "http://identifiers.org/go/GO:0002418"
Reppas2015___tumor_control_via_alternating_immunostimulating_and_immunosuppressive_phases property "http://identifiers.org/mamo/MAMO_0000046"
Reppas2015___tumor_control_via_alternating_immunostimulating_and_immunosuppressive_phases taxon "http://identifiers.org/taxonomy/9606"
