1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/10807517.csml convertedTime:2009.07.01.10:38

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Pathophysiological roles of interleukin-18 in inflammatory liver diseases.
Authors Tsutsui H, Matsui K, Okamura H, Nakanishi K.
Affiliation Department of Immunology and Medical Zoology, Hyogo College of Medicine,Nishinomiya, Japan.
Abstract Innate immune response to microbes sometimes determines the nature of thefollowing specific immune response. Kupffer cells, a potent constituent ofinnate immunity, play a key role in developing the type 1 immune response byinterleukin (IL)-12 production. Furthermore, Kupffer cells have the potential toinduce liver injury by production of IL-18. Propionibacterium acnes-primedlipopolysaccharide (LPS)-challenged liver injury is the prototype ofIL-18-induced tissue injury, in which IL-18 acts on natural killer cells toincrease Fas ligand (FasL) that causes liver injury by induction ofFas-dependent hepatocyte apoptosis. LPS induces IL-18 secretion from Kupffercells in a caspase-1-dependent manner. Indeed, caspase-1-deficient mice areresistant to P. acnes and LPS-induced liver injury. However, administration ofsoluble FasL induces acute liver injury in P. acnes-primed caspase-1-deficientmice but does not do so in IL-18-deficient mice, indicating that IL-18 releasein a caspase-1-independent fashion is essential for this liver injury.Therefore, a positive feedback loop between FasL and IL-18 plays an importantrole in the pathogenesis of endotoxin-induced liver injury.
PMID 10807517
Model Abstract

Entity

e1:NFkappaB e10:IFN-gamma e11:caspase-4 e12:IL-18{inactive} e13:caspase-3{active} e14:caspase-1 e15:caspase-1{active} e16:nitrosyl e17:caspase-1{nitrosylated} e18:FADD e19:FasL e2:JNK{activated} e20:FasL:Fas e21:Fas e22:caspase-8 e23:caspase-8{active} e24:FADD:caspase-8 e25:IL-18R e26:IL-18:IL-18R e27:MyD88 e28:IL-18BP:IL-18 e29:IL-18BP e3:FasL e30:IL-18:IL-18R:MyD88 e31:IRAK e32:MyD88:IRAK e33:IL-1R e34:IL-1 e35:IL-1:IL-1R e36:IL-1:IL-1R:MyD88 e37:MYD88:IRAK{p} e38:TRAF6 e39:IRAK:TRAF6 e4:NFkappB_nucleus e40: e41: e42: e43: e44: e45: e46: e47: e48:IL-12R e49:STAT4 e5:proIL-18 e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:IL-18 e60: e61: e62: e63:STAT4{activated} e64:IL-12 p40 e65:AP-1 e66:AP-1{activated} e67:TNF-alpha e68:TLR4 e69:LPS:TLR4s e7:NFkappaB{activated} e70:IL-18 e71:IL-18 e72:FADD:FasL:Fas e73:caspase-11 e74:IL-12 e75:IL-12:IL-12R e76:TLR2 e77:LPS:TLR2 e78:caspase-3 e8:JNK e9:LPS

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p5 p6 p7 p8 p9
Model Detail
907.125, 568.5
27.75, 45.0

NFkappaB

--

e1

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p18

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false false false

--

Go back
458.5, 899.0
45.0, 24.0

IFN-gamma

--

e10

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false false false

--

Go back
486.25, 529.5
19.5, 45.0

caspase-4

--

e11

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p12

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
480.72076876635134, 595.5778074059165
53.621453008653646, 33.066562688669755

IL-18{inactive}

--

e12

cso30:c:Protein

cso30:i:CC_Cytosol

--

p38

--

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
454.25, 653.5
19.5, 45.0

caspase-3{active}

--

e13

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
427.25, 192.5
19.5, 45.0

caspase-1

--

e14

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p2 p31

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
454.25, 389.5
19.5, 45.0

caspase-1{active}

--

e15

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
306.5, 229.5
45.0, 27.0

nitrosyl

--

e16

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p3

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
319.25, 372.5
19.5, 45.0

caspase-1{nitrosylated}

--

e17

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
207.0, 143.5
42.044676997383775, 25.927550815053333

FADD

--

e18

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
330.5, 16.375
45.0, 29.25

FasL

--

e19

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p4

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
720.5, 698.125
45.0, 33.75

JNK{activated}

--

e2

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false false false

--

Go back
271.375, 71.5
36.170631440473585, 70.00767375575532

FasL:Fas

--

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
410.375, 79.5
40.46792618629174, 62.25834797891037

Fas

--

e21

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p4

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
199.25, 296.5
19.5, 45.0

caspase-8

--

e22

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p6

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
267.25, 396.5
19.5, 45.0

caspase-8{active}

--

e23

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
254.625, 184.5
36.75, 45.0

FADD:caspase-8

--

e24

cso30:c:Complex

cso30:i:CC_Cytosol

--

p6

p5

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
563.375, 72.5
41.587434094903344, 63.98066783831283

IL-18R

--

e25

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p7

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
625.375, 65.5
38.542698969524224, 74.59877219907914

IL-18:IL-18R

--

e26

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
756.5, 138.125
45.0, 33.75

MyD88

--

e27

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
519.75, 21.5
40.5, 45.0

IL-18BP:IL-18

--

e28

cso30:c:Complex

cso30:i:CC_Cytosol

--

p8

p7

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
393.5, 19.125
45.0, 33.75

IL-18BP

--

e29

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p8

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
454.5, 1075.0
45.0, 24.0

FasL

--

e3

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p29

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false false false

--

Go back
678.875, 66.5
52.388741053404296, 73.10056891172692

IL-18:IL-18R:MyD88

--

e30

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
778.5, 233.125
45.0, 27.75

IRAK

--

e31

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p10 p13

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
778.625, 275.5
45.07044659223463, 55.18830194967505

MyD88:IRAK

--

e32

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
941.375, 72.5
39.6225834797891, 60.95782073813708

IL-1R

--

e33

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p11

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
966.5, 21.125
45.0, 27.75

IL-1

--

e34

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p11

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
876.375, 58.5
33.227636483227364, 64.31155448366587

IL-1:IL-1R

--

e35

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
807.875, 64.5
49.79248485960727, 69.47788585061478

IL-1:IL-1R:MyD88

--

e36

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
782.5, 445.0
45.0, 36.0

MYD88:IRAK{p}

--

e37

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
860.5, 370.125
45.0, 33.75

TRAF6

--

e38

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p15

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
777.625, 513.5
41.82065489085153, 51.20896517247125

IRAK:TRAF6

--

e39

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
723.125, 924.5
27.75, 45.0

NFkappB_nucleus

--

e4

cso30:c:Protein

cso30:i:CC_Nucleoplasm

--

p17

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false false false

--

Go back
198.78066238433547, 125.58488526715436
771.5892779955635, 1147.6652555184326

--

e40

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false true false

--

Go back
166.5585367795545, 95.6532280815024
836.0335292051252, 1207.5285698897378

--

e41

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false true false

--

Go back
149.14117158778106, 78.54942397541544
870.868259588672, 1241.7361781019108

--

e42

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false true false

--

Go back
149.14117158778106, 78.54942397541544
870.868259588672, 1241.7361781019108

--

e43

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false true false

--

Go back
160.58311028492525, 83.54626851931816
854.0504448079505, 1188.3810357353761

--

e44

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false true false

--

Go back
171.77078367768848, 125.49382239727458
815.560210950978, 1152.8874001008528

--

e45

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false true false

--

Go back
157.5319266323535, 97.52878647863696
844.1380264638653, 1166.0871700212888

--

e46

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false true false

--

Go back
163.63429393749706, 104.52004545829637
819.3007683732517, 1168.2081573581268

--

e47

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false true false

--

Go back
153.5, 609.0
39.0, 60.0

IL-12R

--

e48

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p32

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
268.5, 717.125
45.0, 27.75

STAT4

--

e49

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p21

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
188.5, 473.125
56.61601931978266, 34.91321191386597

proIL-18

--

e5

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p1 p12 p38

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
333.48351726399363, 794.6571818789603
473.5946281258228, 421.7661284703481

--

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
384.6352648083096, 804.652425972201
276.9249780847457, 408.7753852936433

--

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
339.65700403658354, 800.2865039221989
461.24765458064337, 410.5074843838705

--

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
340.538930718382, 801.1525534673126
459.48380121704605, 408.7753852936433

--

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
333.48351726399363, 794.6571818789603
473.5946281258228, 421.7661284703481

--

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
333.48351726399363, 794.6571818789603
473.5946281258228, 421.7661284703481

--

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
340.538930718382, 801.1525534673126
459.48380121704605, 408.7753852936433

--

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
679.1987765290261, 967.8670909016903
29.587590197687813, 26.30235873831128

--

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
601.5892285307534, 1089.1140272176017
83.7830347708625, 74.48026087977404

--

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
333.48351726399363, 794.6571818789603
473.5946281258228, 421.7661284703481

--

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
505.72076876635134, 474.5778074059165
53.621453008653646, 33.066562688669755

IL-18

--

e6

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
445.1071063796951, 982.0865642889728
14.998045998536096, 7.09127822809305

--

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
444.6062791706111, 960.9386945407812
51.33478893110442, 90.73911554747359

--

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
466.1418491612214, 1019.9560054659676
8.013235345343121, 7.868974790024805

--

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
292.5, 777.125
45.0, 27.75

STAT4{activated}

--

e63

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
424.5, 1023.0
45.0, 24.0

IL-12 p40

--

e64

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p20 p33

--

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
590.5, 849.125
45.0, 27.75

AP-1

--

e65

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p19

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
670.5, 849.125
45.0, 27.75

AP-1{activated}

--

e66

cso30:c:Protein

cso30:i:CC_Cytosol

--

p19

--

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
424.5, 951.0
45.0, 24.0

TNF-alpha

--

e67

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p26

--

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
138.375, 859.5
42.47847100175748, 65.35149384885764

TLR4

--

e68

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p25

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
147.375, 965.5
34.797686910765194, 67.35036176277133

LPS:TLR4s

--

e69

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
827.125, 692.5
27.75, 45.0

NFkappaB{activated}

--

e7

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false false false

--

Go back
465.5, 34.125
45.0, 27.75

IL-18

--

e70

cso30:c:Protein

cso30:i:CC_Extracellular

--

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
486.5, 1127.0
45.0, 24.0

IL-18

--

e71

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p23 p34

--

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
163.5, 73.0
43.0, 60.0

FADD:FasL:Fas

--

e72

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
490.25, 357.5
19.5, 45.0

caspase-11

--

e73

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p31

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
66.5, 561.125
45.0, 27.75

IL-12

--

e74

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p32

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
149.5, 697.0
31.0, 60.0

IL-12:IL-12R

--

e75

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
145.5, 1157.0
39.0, 60.0

TLR2

--

e76

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

p24

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false false false

--

Go back
149.5, 1057.0
31.0, 60.0

LPS:TLR2

--

e77

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false false false

--

Go back
342.25, 717.5
19.5, 45.0

caspase-3

--

e78

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p39

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
642.5, 566.125
45.0, 33.75

JNK

--

e8

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p16

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false false false

--

Go back
45.5, 911.25
45.0, 25.5

LPS

--

e9

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p2 p25 p31 p24

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false false false

--

Go back
359.0, 473.0
35.0, 35.0

p1

p1

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c1 : 1
stoichiometry:c6 : 1
stoichiometry:c2 : 1

m5*m15*0.1

nodelay

--

true

0

false

PMID: 10807517 Murine IL-18 is produced as a biologically inactive precursor of 24 kDa (proIL-18), and proIL-18 is cleaved into biologically active mature IL-18 of 18 kDa by caspase-1, originally designated as IL-1-converting enzyme (ICE).

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694.0, 184.0
30.0, 30.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c32 : 1
stoichiometry:c33 : 1
stoichiometry:c37 : 1

m30*m31*0.1

nodelay

--

true

0

false

PMID: 10807517 After activation with IL-18, IL-18R recruits MyD88, an adapter protein, providing a platform for the IL-1R associated kinase (IRAK).

Go back
898.0, 12.0
30.0, 30.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c34 : 1
stoichiometry:c35 : 1
stoichiometry:c36 : 1

m34*m33*0.1

nodelay

--

true

0

false

PMID: 10807517, 9354477, 9177292, 9514903 IL-18R shares a signal transducing pathway with IL-1R

Go back
362.0, 518.0
35.0, 35.0

p1

p12

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c104 : 1
stoichiometry:c106 : 1
stoichiometry:c20 : 1
stoichiometry:c107 : 1

m5*m11*0.1

nodelay

--

true

0

false

PMID: 10807517, 8999548 Caspase-4 has the capacity to cleave proIL-18 after the 35Asp residue, the same site at which caspase-1 does. However, the efficiency of IL-18 processing by caspase-4 is one hundredth or one thousandth that of caspase-1 (26).

Go back
858.0, 176.0
30.0, 30.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c41 : 1
stoichiometry:c42 : 1
stoichiometry:c38 : 1

m31*m36*0.1

nodelay

--

true

0

false

PMID: 10807517 After activation with IL-18, IL-18R recruits MyD88, an adapter protein, providing a platform for the IL-1R associated kinase (IRAK).

Go back
790.0, 372.0
30.0, 30.0

p14

p14

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m32*0.1

nodelay

--

true

0

false

PMID: 10807517 IRAK subsequently undergoes phosphorylation.

Go back
868.0, 448.0
30.0, 30.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c46 : 1
stoichiometry:c47 : 1
stoichiometry:c39 : 1

m37*m38*0.1

nodelay

--

true

0

false

PMID: 10807517 IRAK subsequently undergoes phosphorylation and interacts with the TNFR-associated factor (TRAF) 6.

Go back
728.0, 604.0
30.0, 30.0

p16

p16

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c50 : 1
stoichiometry:c49 : 1

m8*m39*0.1

nodelay

--

true

0

false

PMID: 10807517, 9354477, 9177292, 9514903 IL-18 does not activate the JAK/STAT system, but activates the IRAK/TRAF6 pathway resulting in the activation of both activator protein (AP)-1 (via JNK) and NFkappaB.

Go back
767.0, 817.0
35.0, 35.0

p17

p17

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e7

e4

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c53 : 1

m7*0.1

nodelay

--

true

0

false

PMID: 10807517 IRAK subsequently undergoes phosphorylation and interacts with the TNFR-associated factor (TRAF) 6, leading to nuclear translocation of NFkappaB.

Go back
826.0, 604.0
30.0, 30.0

p18

p18

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c54 : 1
stoichiometry:c55 : 1
stoichiometry:c56 : 1

m1*m39*0.1

nodelay

--

true

0

false

PMID: 10807517, 9354477, 9177292, 9514903 IL-18 does not activate the JAK/STAT system, but activates the IRAK/TRAF6 pathway resulting in the activation of both activator protein (AP)-1 (via JNK) and NFkappaB.

Go back
646.0, 792.0
30.0, 30.0

p19

p19

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c51 : 1
stoichiometry:c67 : 1

m65*m2*0.1

nodelay

--

true

0

false

PMID: 10807517, 9354477, 9177292, 9514903 IL-18 does not activate the JAK/STAT system, but activates the IRAK/TRAF6 pathway resulting in the activation of both activator protein (AP)-1 (via JNK)

Go back
378.0, 292.0
30.0, 30.0

p2

p2

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c3 : 1
stoichiometry:c98 : 1
stoichiometry:c4 : 1

m14*m9*0.1

nodelay

--

true

0

false

PMID: 10807517, 9427712 LPS has been reported to have the capacity to induce the activation of caspase-1.

Go back
348.0, 1016.0
30.0, 30.0

p20

p20

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c66 : 1

m69*0.1

nodelay

--

true

0

false

PMID: 10807517, 11513148 mRNA for IL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge.

Go back
220.0, 780.0
30.0, 30.0

p21

p21

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c62 : 1
stoichiometry:c90 : 1
stoichiometry:c63 : 1

m49*m75*0.1

nodelay

--

true

0

false

PMID: 10807517, 8670419, 7722452 IL-12 activates STAT4.

Go back
352.0, 896.0
30.0, 30.0

p22

p22

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c60 : 1

m69*0.1

nodelay

--

true

0

false

PMID: 10807517 First, mRNA forIL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge. Second,the hepatic IFN-gamma mRNA level is enhanced soon after the elevation of IL-12 p40.

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410.0, 1120.0
30.0, 30.0

p23

p23

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c78 : 1

m69*0.1

nodelay

--

true

0

false

PMID: 10807517 IL-18 gene expression may be upregulated by the direct stimulation with microbial products such as LPS

Go back
90.0, 1100.0
30.0, 30.0

p24

p24

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c59 : 1
stoichiometry:c68 : 1
stoichiometry:c91 : 1

m9*m76*0.1

nodelay

--

true

0

false

PMID: 10807517, 10500213, 10201887, 10549626, 9751057, 9841923, 10426996 LPS is recognized by TLR-4 in mouse and TLR-2 in human.

Go back
93.0, 961.0
30.0, 30.0

p25

p25

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c69 : 1
stoichiometry:c70 : 1

m9*m68*0.1

nodelay

--

true

0

false

PMID: 10807517, 10500213, 10201887, 10549626, 9751057, 9841923, 10426996 LPS is recognized by TLR-4 in mouse and TLR-2 in human.

Go back
521.0, 949.0
30.0, 30.0

p26

p26

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c73 : 1

m10*0.1

nodelay

--

true

0

false

PMID: 10807517 LPS challenge seems to induce rapid secretion of both IL-18 and IL-12 from Kupffer cells, which cause hepatic lymphocytes to produce a huge amount of IFN- gamma, leading to the second elevation of TNF-alpha.

Go back
396.0, 852.0
30.0, 30.0

p27

p27

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c65 : 1

m63*0.1

nodelay

--

true

0

false

PMID: 10807517, 8670419, 7722452 IL-12 activates STAT4, a member of the STAT family,which induces the activation of IFN-gamma gene expression through binding of STAT4 to the corresponding binding site in the IFN-gamma promoter region.

Go back
494.0, 832.0
30.0, 30.0

p28

p28

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c77 : 1

m26*0.1

nodelay

--

true

0

false

PMID: 10807517 After LPS challenge, IL-18 is secreted from Kupffer cells, which initiates the ordered action of IFN-alpha and TNF-alpha.

Go back
534.0, 1044.0
30.0, 30.0

p29

p29

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c81 : 1
stoichiometry:c80 : 1

m26*0.1

nodelay

--

true

0

false

PMID: 10807517 IL-18 accumulated in the liver also induces FasL expression on hepatic effector cells

Go back
314.0, 292.0
30.0, 30.0

nitrosylation

p3

cso30:i:ME_Nitrosylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m16*m15*0.1

nodelay

--

true

0

false

PMID: 10807517, 9034139, 9388494 Enzyme activities of some caspases including caspase-1 are reversibly downregulated by nitric oxide (NO), via direct S-nitrosylation of caspase catalytic cysteine residues . Downmodulation of caspase-1 by NO results in reduction of IL-1 and IL-18 secretion from LPS-activated macrophages (59), suggesting a possible negative feedback of IL-18 production by NO.

Go back
206.0, 16.0
30.0, 30.0

p30

p30

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c79 : 1
stoichiometry:c82 : 1

m20*m18*0.1

nodelay

--

true

0

false

PMID: 10807517 The activation of Fas recruits an adaptor molecule, Fas-associated death domain protein, which binds to and activates caspase-8

Go back
462.0, 296.0
30.0, 30.0

p31

p31

cso30:i:ME_Autocleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c87 : 1
stoichiometry:c99 : 1
stoichiometry:c85 : 1

m14*m73*m9*0.1

nodelay

--

true

0

false

PMID: 10807517, 9491891 Precursor caspase-1 is cleaved into its mature form by caspase-11 or autoproteolytically.

Go back
70.0, 624.0
30.0, 30.0

p32

p32

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c88 : 1
stoichiometry:c89 : 1

m74*m48*0.1

nodelay

--

true

0

false

PMID: 10807517, 8670419, 7722452 IL-12 activates STAT4, a member of the STAT family, which induces the activation of IFN-gamma gene expression

Go back
353.0, 1053.0
30.0, 30.0

p20

p33

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c92 : 1

m77*0.1

nodelay

--

true

0

false

PMID: 10807517, 11513148 mRNA for IL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge.

Go back
489.0, 1165.0
30.0, 30.0

p23

p34

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c94 : 1

m77*0.1

nodelay

--

true

0

false

PMID: 10807517 IL-18 gene expression may be upregulated by the direct stimulation with microbial products such as LPS

Go back
345.0, 949.0
30.0, 30.0

p22

p35

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c97 : 1
stoichiometry:c96 : 1

m77*0.1

nodelay

--

true

0

false

PMID: 10807517 First, mRNA forIL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge. Second,the hepatic IFN-gamma mRNA level is enhanced soon after the elevation of IL-12 p40.

Go back
493.0, 229.0
30.0, 30.0

p36

p36

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c101 : 1

m6*0.1

nodelay

--

true

0

false

PMID: 10807517 After LPS challenge, IL-18 is secreted from Kupffer cells, which initiates the ordered action of IFN-alpha and TNF-alpha.

Go back
801.0, 189.0
30.0, 30.0

p9

p37

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c103 : 1
stoichiometry:c25 : 1

m27*m35*0.1

nodelay

--

true

0

false

PMID: 10807517, 10227969, 9759857, 10653850 When IL-18R or IL-1R is activated by corresponding ligand, MyD88 is recruited to the intracellular domain of each receptor.

Go back
362.0, 578.0
35.0, 35.0

p1

p38

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c105 : 1
stoichiometry:c109 : 1
stoichiometry:c113 : 1
stoichiometry:c108 : 1

m5*m13*0.1

nodelay

--

true

0

false

PMID: 10807517, 8999548, 9334240 Caspase-3 can also cleave IL-18, but at a different site, 69Asp-70Ile, resulting in the accumulation of biologically inactive products (26, 61).

Go back
401.0, 717.0
30.0, 30.0

p39

p39

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c110 : 1
stoichiometry:c112 : 1
stoichiometry:c111 : 1

m78*m23*0.1

nodelay

--

true

0

false

PMID: 10807517, 8706881, 9463409, 10235259, 9917913 The activated caspase-8 then sequentially activates downstream caspases, such as caspase-3, 6 and 7 (67?70).

Go back
338.0, 88.0
30.0, 30.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c14 : 1
stoichiometry:c13 : 1

m19*m21*0.1

nodelay

--

true

0

false

PMID: 10807517 The activation of Fas recruits an adaptor molecule, Fas-associated death domain protein, which binds to and activates caspase-8

Go back
258.0, 304.0
30.0, 30.0

p5

p5

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c16 : 1
stoichiometry:c86 : 1

m24*0.1

nodelay

--

true

0

false

PMID: 10807517, 10514014 caspase-1-deficient mice secreted biologically active IL-18 after stimulation with membrane-associated FasL or soluble FasL

Go back
194.0, 212.0
30.0, 30.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c83 : 1
stoichiometry:c18 : 1
stoichiometry:c5 : 1

m22*m72*0.1

nodelay

--

true

0

false

PMID: 10807517, 9521326, 8681377 The activation of Fas recruits an adaptor molecule, Fas-associated death domain protein, which binds to and activates caspase-8

Go back
537.0, 161.0
30.0, 30.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c27 : 1
stoichiometry:c72 : 1
stoichiometry:c23 : 1

m25*m70*0.1

nodelay

--

true

0

false

PMID: 10807517 IL-18 BP prevents mature IL-18 from binding to its authentic receptor IL-18R,

Go back
457.0, 101.0
30.0, 30.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c102 : 1
stoichiometry:c26 : 1

m29*m70*0.1

nodelay

--

true

0

false

PMID: 10807517 IL-18 BP has the capacity to bind to IL-18 without exhibiting species specificity.

Go back
734.0, 8.0
30.0, 30.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c29 : 1
stoichiometry:c30 : 1

m26*m27*0.1

nodelay

--

true

0

false

PMID: 10807517, 10227969, 9759857, 10653850 When IL-18R or IL-1R is activated by corresponding ligand, MyD88 is recruited to the intracellular domain of each receptor.

Go back
245.0, 491.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
339.0, 414.0

c10

c10

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
509.81062105283695, 266.95882488239926

c100

c100

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
489.8101843054786, 69.95886935381881

c101

c101

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
477.79887605359005, 62.0

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
830.4788592902239, 115.0

c103

c103

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
245.0, 499.0

c104

c104

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
244.0, 508.0

c105

c105

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
404.91599903935696, 539.1562695226027

c106

c106

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
397.0, 501.25351763428034

c107

c107

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
397.0, 598.0

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
402.75695169577983, 617.5549533906648

c109

c109

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
333.0, 805.0

c11

c11

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
362.0, 735.017314527883

c110

c110

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
429.0, 693.145770236779

c111

c111

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
287.0, 441.0

c112

c112

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
335.0, 418.0

c113

c113

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
353.0, 46.0

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
315.9822812628529, 104.0

c13

c13

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
375.9639637807516, 105.75847274102397

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
239.28824434455197, 52.00287195868062

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
274.0, 334.0

c16

c16

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
209.0, 250.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
224.0, 215.23048155891163

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
273.0, 230.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
394.0, 491.0

c2

c2

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
337.0, 418.0

c20

c20

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
561.2219089141281, 136.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
792.0, 172.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
567.0, 122.97115768801635

c23

c23

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
428.0, 53.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
819.0, 141.89499666318198

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
486.0, 70.81610522039854

c26

c26

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
542.0, 67.0

c27

c27

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
664.0, 39.88642763433457

c28

c28

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
753.7931815433714, 45.7964414929192

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
403.42469075791234, 235.0

c3

c3

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
728.8646187432906, 38.0

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
706.0, 140.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
731.1293049248119, 210.6294643253588

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
722.0, 214.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
935.9582515088885, 29.816230923988556

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
926.1804964634343, 48.82081001928754

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
905.2573305919324, 42.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
668.4084922779336, 137.67571687801387

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
876.0, 130.83307069973395

c38

c38

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
809.9999208944645, 155.0355764291395

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
403.0, 322.0

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
819.0, 207.87768608679755

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
848.0, 134.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
823.2573723617468, 206.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
802.0, 331.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
805.0, 402.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
828.0, 463.0

c45

c45

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
883.0, 404.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
824.952389692232, 476.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
688.0, 593.0

c48

c48

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
743.0, 634.0

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
219.0, 139.68231441047038

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
758.5536798306425, 565.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
679.3517178529796, 732.0

c51

c51

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
797.3931212784858, 738.0

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
750.1269890331363, 852.0

c53

c53

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
863.5439226686631, 596.0

c54

c54

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
812.0, 565.0

c55

c55

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
841.0, 634.0

c56

c56

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
625.0, 828.0899458438937

c57

c57

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
494.0, 923.0

c58

c58

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
70.0, 937.0

c59

c59

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
399.89723312160595, 421.0

c6

c6

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
382.0, 911.0

c60

c60

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
78.0, 937.0

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
253.30428196236983, 745.0

c62

c62

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
250.0, 792.3716911948197

c63

c63

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
86.4563983243081, 589.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
426.0, 876.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
378.0, 1032.0

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
670.0, 822.0

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
123.17581958556076, 1136.1000730829824

c68

c68

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
121.1716000756318, 925.0

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
329.0, 257.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
123.0, 982.0

c70

c70

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
182.0, 920.1929641058495

c71

c71

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
495.0, 62.0

c72

c72

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
477.9984625732538, 963.1568325994756

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
182.0, 1002.0

c74

c74

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
182.0, 1008.0

c75

c75

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
513.4330852291622, 140.0

c76

c76

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
489.17528920548375, 862.0

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
440.0, 1136.0

c78

c78

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
222.40763305897528, 53.98960795591564

c79

c79

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
350.33028001113735, 323.8915800086061

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
507.47241467880866, 1065.0

c80

c80

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
551.7925421415944, 140.0

c81

c81

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
203.4705249501832, 46.0

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
191.0, 133.0

c83

c83

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
446.0, 238.0

c84

c84

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
467.9922778767137, 326.0

c85

c85

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
234.11460940376443, 176.7154667434648

c86

c86

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
484.3861999450876, 333.63583982428025

c87

c87

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
108.0, 639.0

c88

c88

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
99.0, 654.0

c89

c89

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
329.0, 322.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
181.0, 742.0

c90

c90

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
120.0, 1097.383083722649

c91

c91

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
383.0, 1047.1513543886333

c92

c92

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
181.0, 1069.7868636606042

c93

c93

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
505.0, 1158.9195959492893

c94

c94

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
181.0, 1091.0

c95

c95

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
375.0, 924.1513543886333

c96

c96

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
181.0, 977.2843362028667

c97

c97

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
75.0, 329.07934577905587

c98

c98

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
77.0, 332.6564023547028

c99

c99

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back