1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/1916089.csml convertedTime:2009.07.01.11:22

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Gram-negative endotoxin: an extraordinary lipid with profound effects oneukaryotic signal transduction.
Authors Raetz CR, Ulevitch RJ, Wright SD, Sibley CH, Ding A, Nathan CF.
Affiliation Department of Biochemistry, Merck Sharp and Dohme Research Laboratories, Rahway,New Jersey 07065.
Abstract The lipid A domain of lipopolysaccharide (LPS) is a unique, glucosamine-basedphospholipid that makes up the outer monolayer of the outer membrane of mostgram-negative bacteria. Because of its profound pharmacological effects onanimal cells, especially those of the immune system, lipid A is also known asendotoxin. Despite decades of earlier work, the precise chemistry of endotoxinsand the biochemical pathways for their enzymatic synthesis have been elucidatedonly within the past 5 years. In this review, we summarize the essentials ofendotoxin biochemistry and also present recent experiments aimed at identifyingsurface receptors, signal-transducing elements, transcriptional factors, and keyintracellular targets involved in the response of animal cells to endotoxins.
PMID 1916089
Model Abstract

Entity

e1: e10: e11:LPS:LBP e12:CD18 e13:LPS:CD18 e14:Lipid A e15:acetylated LDL receptor e16:Lipid A:LDL receptor e17:TNF e18:TNF e19:IL-1beta e2: e20:CD14 e21:LPS:LBP:CD14 e22:anti CD14 e23:NF-kappaB:IkappaB e24:NF-kappaB{active} e25:IkappaB e26:OTF2 e27:kappa e28:NF-kappaB{active} e29:TGF-beta e3: e30:OTF2 e31:TNFR e32:TNFR e33:PMA e4: e5:LPS e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:LBP e60: e61: e62: e7: e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p2 p3 p4 p5 p6 p7 p8 p9
Model Detail
91.28601681191245, 52.72026303178758
781.8667776263562, 1102.7346334396848

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
98.8192487747475, 69.575051288743
757.8683358317668, 1035.55387260901

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
1056.5, 420.15797367105483
39.070988168638564, 47.842026328945174

LPS:LBP

--

e11

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
828.5, 142.0
39.0, 60.0

CD18

--

e12

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p2

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
836.5, 250.0
31.0, 60.0

LPS:CD18

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p2

p5

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
1158.0, 59.0
60.0, 34.0

Lipid A

--

e14

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p3

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
951.0, 51.0
65.89923023093071, 50.522743177046884

acetylated LDL receptor

--

e15

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p3

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
1171.5, 135.3482752874521
40.548908515247454, 49.65172471254791

Lipid A:LDL receptor

--

e16

cso30:c:Complex

cso30:i:CC_Extracellular

--

p3

--

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
466.0, 816.0
60.0, 32.0

TNF

--

e17

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p4 p8

p5

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
695.0, 753.6601931978264
51.63211913865969, 31.83980680217347

TNF

--

e18

cso30:c:Protein

cso30:i:CC_Cytosol

--

p5

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
350.0, 740.0
60.0, 32.0

IL-1beta

--

e19

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p6

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
91.28601681191245, 52.72026303178758
781.8667776263562, 1102.7346334396848

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
824.5, 498.0
39.0, 60.0

CD14

--

e20

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p7

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
818.5, 594.0
43.0, 60.0

LPS:LBP:CD14

--

e21

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
942.0, 554.076923076923
28.615384615384613, 42.92307692307692

anti CD14

--

e22

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p7

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
325.5, 398.0
36.441759706715544, 44.62256290618231

NF-kappaB:IkappaB

--

e23

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p9 p15

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
545.0, 402.82000000000005
46.239999999999995, 34.68000000000001

NF-kappaB{active}

--

e24

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
526.0, 305.5
60.0, 37.0

IkappaB

--

e25

cso30:c:Protein

cso30:i:CC_Cytosol

--

p9 p15

--

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
280.02768166089965, 854.9480968858131
61.97231833910035, 33.05190311418686

OTF2

--

e26

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
490.0, 896.0
60.0, 32.0

kappa

--

e27

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p11

--

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
389.0, 867.1799999999998
45.76, 34.32

NF-kappaB{active}

--

e28

cso30:c:Protein

cso30:i:CC_Nucleoplasm

--

p12

--

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
917.5, 970.0
37.0, 60.0

TGF-beta

--

e29

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p10 p13

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
106.92335236443954, 67.9094453105711
750.592106521302, 1072.3562688821185

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
179.0, 772.6877641376534
49.9657878848863, 30.81223586234655

OTF2

--

e30

cso30:c:Protein

cso30:i:CC_Cytosol

--

p13

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
828.5, 878.0
39.0, 60.0

TNFR

--

e31

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p14

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
699.5, 861.8734622144112
33.88224956063269, 52.12653778558875

TNFR

--

e32

cso30:c:Protein

cso30:i:CC_Cytosol

--

p14

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
346.0, 259.0
60.0, 34.0

PMA

--

e33

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p15

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
135.8524231366148, 94.49051429844219
692.7339649769516, 1019.1941309063757

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
1090.0, 327.0
60.0, 34.0

LPS

--

e5

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p1 p2

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
256.7888402378346, 688.665997593667
425.1939391714468, 374.55308565379767

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
302.71295284853073, 697.5423612091234
248.62364413376972, 363.01654297452257

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
262.33140555291857, 693.6651660880195
414.10880854127896, 364.5547486650926

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
263.1232005979306, 694.4342689333043
412.5252184512546, 363.01654297452257

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
256.7888402378346, 688.665997593667
425.1939391714468, 374.55308565379767

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
256.7888402378346, 688.665997593667
425.1939391714468, 374.55308565379767

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
263.1232005979306, 694.4342689333043
412.5252184512546, 363.01654297452257

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
567.1724978825405, 842.486566650668
26.56378108960103, 23.358038876040816

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
497.49453392148394, 950.1609649905688
75.22052927614048, 66.14284469451049

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
256.7888402378346, 688.665997593667
425.1939391714468, 374.55308565379767

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
914.0, 325.5
60.0, 37.0

LBP

--

e6

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
357.0046592989216, 855.1142939005888
13.465267296692984, 6.297471423783565

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
356.55501590934733, 836.333743888388
46.08844743135914, 80.5816622616534

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
375.8896816610401, 888.7445811317399
7.194294233187762, 6.988111632446902

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
101.55860585214205, 57.15775437145233
766.7677192963048, 1055.352134324922

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
104.29796292953665, 75.78369974738837
735.5694097490158, 1037.4374338957514

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
111.60291513592213, 94.40964512332445
732.2111319083912, 1023.831701908508

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
1017.0, 333.0
21.0, 21.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1

m6*m5*0.1

nodelay

--

true

0

false

PMID: 1916089, 2471708 The binding specificity of LBP for LPS is for the lipid A moiety. Accordingly, LBP binds to LPS isolated from rough and smooth forms of bacteria.

Go back
301.0, 792.0
23.0, 23.0

p10

p10

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c34 : 1
stoichiometry:c28 : 1

m21*0.1

nodelay

--

true

0

false

PMID: 1916089, 3399892 OTF-2 levels increase slowly after LPS treatment, and its augmentation represents an increase in the steady-state level of the mRNA that encodes it. PMID: 1916089 Transforming growth factor-fl specifically prevents the increase in steady-state levels of OTF-2 protein and mRNA normally observed after LPS treatment of 70Z/3 cells.

Go back
558.0, 846.0
27.0, 27.0

p11

p11

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c30 : 1
stoichiometry:c29 : 1

m21*0.1

nodelay

--

true

0

false

PMID: 1916089, 6322127 There is a 30- to 50-fold increase in kappa transcription.

Go back
525.0, 520.0
23.0, 23.0

p12

p12

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c33 : 1
stoichiometry:c32 : 1

m24*m21*0.1

nodelay

--

true

0

false

PMID: 1916089 Normal cells show huge increases in the level of nuclear NF-KB minutes after LPS treatment.

Go back
190.0, 858.0
27.0, 27.0

p13

p13

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c37 : 1
stoichiometry:c38 : 1
stoichiometry:c36 : 1

m26*m21*0.1

nodelay

--

true

0

false

PMID: 1916089 Transforming growth factor-fl specifically prevents the increase in steady-state levels of OTF-2 protein and mRNA normally observed after LPS treatment of 70Z/3 cells.

Go back
757.0, 893.0
21.0, 21.0

p14

p14

cso30:i:ME_Internalization

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c39 : 1
stoichiometry:c41 : 1
stoichiometry:c40 : 1

m31*m21*0.1

nodelay

--

true

0

false

PMID: 1916089 LPS may accelerate the internalization of TNF-R faster than TNF-R can be replaced.

Go back
424.0, 352.0
23.0, 23.0

p15

p15

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c42 : 1
stoichiometry:c45 : 1
stoichiometry:c43 : 1
stoichiometry:c44 : 1

m23*m33*0.1

nodelay

--

true

0

false

PMID: 1916089, 3096580 The activation of NF-xB from the cytoplasm can be mimicked by treatment of the cells with phorbol 12-myristate 13-acetate.

Go back
966.0, 162.0
20.0, 20.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1

m12*m5*0.1

nodelay

--

true

0

false

PMID: 1916089,3537192 CD18 molecules bind particulate LPS when presented on the surface of bacteria or LPS-coated erythrocytes.

Go back
1066.0, 66.0
19.0, 19.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1

m15*m14*0.1

nodelay

--

true

0

false

PMID: 1916089, 1852209 The acetylated LDL (scavenger) receptors, recently cloned, are capable of binding lipid A.

Go back
481.0, 746.0
25.0, 25.0

p4

p4

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c10 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 1916089, 1698311 Moreover, antibodies against CD18 do not prevent synthesis of TNF by normal monocytes in response to LPS. PMID: 1916089 In studies with primary cultures of rabbit peritoneal exudate macrophages (PEM) or with vitamin D3-differentiated THP-1 cells, it was found that LBP-LPS complexes were as much as 1000-fold more active than LPS alone in induction of monokines such as TNF or IL 1beta.

Go back
743.0, 819.0
26.0, 26.0

p5

p5

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c13 : 1
stoichiometry:c12 : 1

m17*m13*0.1

nodelay

--

true

0

false

PMID: 1916089, 1698311 Moreover, antibodies against CD18 do not prevent synthesis of TNF by normal monocytes in response to LPS.

Go back
449.0, 706.0
25.0, 25.0

p6

p6

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c15 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 1916089 In studies with primary cultures of rabbit peritoneal exudate macrophages (PEM) or with vitamin D3-differentiated THP-1 cells, it was found that LBP-LPS complexes were as much as 1000-fold more active than LPS alone in induction of monokines such as TNF or IL 1beta.

Go back
929.0, 461.0
21.0, 21.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c18 : 1
stoichiometry:c20 : 1
stoichiometry:c19 : 1

m20*m11*0.1

nodelay

--

true

0

false

PMID: 1916089 When CDI4 was purified from detergent lysates of macrophages by absorption onto surfaces coated with this antibody, the CD14-coated surfaces retained the ability to bind LPS-LBP complexes, indicating that purified CD14 is sufficient for binding of LPS-LBP complexes. PMID: 1916089, 1698311 Surface-bound antibodies against CDI4, but not antibodies against other antigens, down-modulated the binding of erythrocytes coated with LPS-LBP complexes to macrophages.

Go back
552.0, 764.0
23.0, 23.0

p8

p8

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c21 : 1

m21*0.1

nodelay

--

true

0

false

PMID: 1916089 The ligated CD14 may then directly trigger the synthesis of TNF.

Go back
432.0, 408.5
23.5, 23.5

p9

p9

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c26 : 1
stoichiometry:c25 : 1
stoichiometry:c24 : 1

m23*m21*0.1

nodelay

--

true

0

false

PMID: 1916089, 3129195 The NF-xB is found in almost all cells as an inactive complex, held in the cytoplasm by an inhibitor, IxB. After treatment of the cells with LPS, NF-xB activation is extremely rapid.

Go back
974.0, 344.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
494.0, 771.0

c10

c10

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
526.0, 832.0

c11

c11

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
733.9025708613195, 791.9835478570981

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
759.3779159787705, 310.0

c13

c13

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
513.0367856105216, 455.0

c14

c14

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
417.2636750760036, 725.0

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
481.3016857531581, 453.0

c16

c16

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
864.0, 483.0375726986492

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
957.8360815016773, 448.0

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
864.368316725511, 482.0

c19

c19

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1046.0, 344.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
941.6041015949661, 485.9541195306869

c20

c20

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
521.2140459897561, 786.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
582.0121529180356, 636.0

c22

c22

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
362.0, 420.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
456.0, 420.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
456.0, 348.21273531622023

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
463.11179645141283, 429.6636527173945

c26

c26

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
331.57091292046397, 631.0

c27

c27

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
312.1999375292816, 815.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
541.6568542494924, 873.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1033.0, 354.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
591.0046899112375, 643.0

c30

c30

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
542.1605234491949, 438.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
420.6759454254083, 543.0

c32

c32

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
555.6571451445357, 537.316922147055

c33

c33

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
327.8153970029568, 808.2011435009308

c34

c34

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
224.99899237986878, 871.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
204.0, 812.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
220.93981131548037, 874.6912935689074

c37

c37

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
224.45231414908994, 632.0

c38

c38

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
785.9861949854, 904.4697761756117

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
868.0, 172.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
740.68, 895.24

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
772.9784181205587, 654.0

c41

c41

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
362.0, 375.1804964634343

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
447.0, 369.0

c43

c43

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
447.0, 336.500946763044

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
388.0, 293.0

c45

c45

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
989.1504854207755, 188.12147857387245

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
874.0130055125634, 181.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1017.0, 76.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1093.0, 76.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1085.0, 82.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back