1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/9917870.csml convertedTime:2009.07.01.11:24

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Afferent pathways of pyrogen signaling.
Authors Blatteis CM, Sehic E, Li S.
Affiliation Department of Physiology and Biophysics, University of Tennessee, Memphis 38163,USA. blatteis@physiol.utmem.edu
Abstract We and others recently showed that fever induced by intravenously orintraperitoneally injected lipopolysaccharide (LPS) may involve brain signalingvia hepatic vagal afferents. This suggests that LPS fever may be initiated bymediators released mainly by cells in the liver, presumably macrophages (Kupffercells, Kc). To verify this possibility, we disabled the Kc of conscious guineapigs with gadolinium chloride and monitored their core temperature andassociated preoptic prostaglandin E2 (PGE2) responses to i.v. LPS. Gadoliniumchloride pretreatment significantly attenuated both the febrile and PGE2 rises,thus supporting the hypothesis. Additionally, fluorescein-labeled LPS wasdetected in Kc 15 minutes after its i.v. administration. Paradoxically, however,the label was also present in gadolinium chloride-pretreated guinea pigs. Thus,either Kc are not the primary source of pyrogenic mediators or LPS does notprovide the stimulus for their production. Because the i.v. injection of LPSelicits virtually immediately the production of complement fragments, and Kcexpress their receptors and produce various mediators on their activation, wehypocomplemented guinea pigs with cobra venom factor. The core temperature risesproduced by i.v. LPS were reduced by complement depletions > 60%. LPS i.v. perse decreased complement, that is, complement was consumed by 12% within 10minutes. Thus, the onset of LPS fever may involve complement system and Kcactivation, but their precise roles await clarification.
PMID 9917870
Model Abstract

Entity

e1: e10: e12:IL-1beta e13:IL-6 e14:IL-1beta e15:IL-6 e16:cox-2 e17:COX-2 e18:PGE2 e19:Indomethacin e2: e20:c-fos e21:C-FOS e22:PGE2EP1 receptor e23:IL-1 e24:cPLA2 e25:PGE2EP3 receptor e26:IL-1RI e27:cPLA2 e28:cPLA{active} e29:Phopholipids e3: e30:arachidonic acid e31:C3a e33:complement e34:TNF-alpha e35:TNF-alpha e36:EP3 e37:Phosphoinositide e38:cox1 e39:PI-PLC{active} e4: e40:PI-PLC e42:C5b-9 e43:C5a e44:complement{active} e45:C components e46:C component receptor e47:C component receptor: C components e48:PGE2 receptors e49:PGE2: PGE2 receptors e5:LPS e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e60: e61: e62: e7: e8: e9:

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 p40 p41 p5 p6 p7 p8 p9
Model Detail
14.75, 1.9969080091175897
1030.3942648349378, 1496.132472540327

--

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
23.0, 64.0
1016.1035952252828, 1429.372045829534

--

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
410.0, 460.0
60.0, 32.0

IL-1beta

--

e12

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p2 p4 p25

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
426.0, 548.0
60.0, 32.0

IL-6

--

e13

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p1 p5 p6

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
696.0, 232.5
47.31107205623901, 30.75219683655536

IL-1beta

--

e14

cso30:c:Protein

cso30:i:CC_Cytosol

--

p2 p4 p25

p1 p8 p10 p13 p15 p28 p37 p39

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
920.0, 500.5
40.96000000000001, 30.720000000000006

IL-6

--

e15

cso30:c:Protein

cso30:i:CC_Cytosol

--

p1 p5 p6

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
510.0, 768.0
60.0, 32.0

cox-2

--

e16

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p7 p8

p9 p19

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
905.5, 757.0
28.920909639766556, 46.89877238881063

COX-2

--

e17

cso30:c:Protein

cso30:i:CC_Cytosol

--

p9 p19

p20

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
714.0, 1039.0
60.0, 34.0

PGE2

--

e18

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

p10 p20 p24 p16 p21 p22 p23

p25 p26 p35 p34 p38 p41

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
834.0, 999.0
60.0, 34.0

Indomethacin

--

e19

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p10

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
14.75, 1.9969080091175897
1030.3942648349378, 1496.132472540327

--

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
358.0, 884.0
60.0, 32.0

c-fos

--

e20

cso30:c:mRNA

cso30:i:CC_Nucleolus

--

p39 p40 p41

p11

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
684.0, 1109.0
23.069223573433113, 53.236669784845645

C-FOS

--

e21

cso30:c:Protein

cso30:i:CC_Cytosol

--

p11

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
534.0, 828.0
60.0, 32.0

PGE2EP1 receptor

--

e22

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p13

--

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
406.0, 620.0
60.0, 32.0

IL-1

--

e23

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p12

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
302.0, 792.0
60.0, 32.0

cPLA2

--

e24

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p14 p15

p18

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
234.0, 564.0
60.0, 32.0

PGE2EP3 receptor

--

e25

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p34

--

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
226.0, 664.0
60.0, 32.0

IL-1RI

--

e26

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p36 p37 p38

--

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
832.0, 165.5
48.16663312537733, 29.702757093982694

cPLA2

--

e27

cso30:c:Protein

cso30:i:CC_Cytosol

--

p18

p17

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
744.0, 193.5
48.33568122358623, 29.80700342121151

cPLA{active}

--

e28

cso30:c:Protein

cso30:i:CC_Cytosol

--

p17

p3

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
682.0, 23.0
60.0, 34.0

Phopholipids

--

e29

cso30:c:SmallMolecule

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p3

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
35.35788529669874, 22.60479330581637
989.1784942415401, 1454.916701946931

--

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
566.0, 111.0
60.0, 34.0

arachidonic acid

--

e30

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p29 p3

p20 p24

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
1081.0, 1187.5
53.92634332863755, 33.25457838599316

C3a

--

e31

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p21

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
1266.0, 142.5
43.31253773395049, 26.70939826926947

complement

--

e33

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p30 p31

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
266.0, 892.0
60.0, 32.0

TNF-alpha

--

e34

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p26

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
477.5, 1154.0
37.0, 60.0

TNF-alpha

--

e35

cso30:c:Protein

cso30:i:CC_Cytosol

--

p26

p4 p6

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
206.0, 500.0
60.0, 32.0

EP3

--

e36

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p27 p28

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
978.0, 895.0
60.0, 34.0

Phosphoinositide

--

e37

cso30:c:SmallMolecule

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p29

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
374.0, 117.0
20.053320860617397, 46.276894293732454

cox1

--

e38

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p24

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
757.0, 1206.5
45.919999999999995, 34.43999999999999

PI-PLC{active}

--

e39

cso30:c:Protein

cso30:i:CC_Cytosol

--

p30

p29

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
73.48247309559153, 58.668592575038986
912.9293186437554, 1382.7891034084848

--

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
614.0, 1237.5
50.4, 37.800000000000004

PI-PLC

--

e40

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p30

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
1100.0, 1329.0
23.762394761459305, 54.83629560336763

C5b-9

--

e42

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p23

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
1091.0, 1260.5
42.24, 31.68

C5a

--

e43

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p22

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
1227.0, 35.5
42.02052726906821, 25.912658482592068

complement{active}

--

e44

cso30:c:Protein

cso30:i:CC_Extracellular

--

p31

p32

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
1138.0, 150.5
44.04910444757496, 27.163614409337892

C components

--

e45

cso30:c:Protein

cso30:i:CC_Extracellular

--

p32

p33

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
968.5, 22.0
39.0, 60.0

C component receptor

--

e46

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p33

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
988.5, 118.0
31.0, 60.0

C component receptor: C components

--

e47

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p33

p16

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
984.5, 974.0
39.0, 60.0

PGE2 receptors

--

e48

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p35

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
984.5, 1082.0
39.0, 60.0

PGE2: PGE2 receptors

--

e49

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p35

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
1121.0, 295.0
45.49201009251472, 25.778805719091675

LPS

--

e5

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p5 p7 p11 p12 p14 p17 p19 p25 p26 p27 p31 p36 p40

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
110.05263558486732, 376.41385399343153
731.299220988777, 663.2080458501578

--

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
189.0383987456661, 392.13092052723556
427.6125798705326, 642.7806933085723

--

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
119.5854001042741, 385.2657067614521
712.2336919499637, 645.5043403141168

--

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
120.94722360704645, 386.62753026422456
709.5100449444187, 642.7806933085723

--

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
110.05263558486732, 376.41385399343153
731.299220988777, 663.2080458501578

--

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
110.05263558486732, 376.41385399343153
731.299220988777, 663.2080458501578

--

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
120.94722360704645, 386.62753026422456
709.5100449444187, 642.7806933085723

--

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
643.8874486716463, 648.7785545479112
45.68755720082987, 41.359262308119725

--

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
524.0469804276767, 839.4338449360466
129.37323276337773, 117.11682123842628

--

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
110.05263558486732, 376.41385399343153
731.299220988777, 663.2080458501578

--

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
282.41574723442966, 671.1380294360451
23.15917179738226, 11.150712346887765

--

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
281.6423969341895, 637.8839665257319
79.26840577458191, 142.68313039424748

--

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
314.8964598445026, 730.6860025545105
12.373604803837168, 12.373604803837173

--

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
200.0, 9.0
839.7237354966342, 1189.8668429177399

--

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
45.0, 30.0
805.5569854171277, 1169.6687428256696

--

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
53.0, 51.0
801.8791759029863, 1154.3288303559784

--

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
825.0, 521.0
30.0, 30.0

p1

p1

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

e13 e14

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c18 : 1
stoichiometry:c4 : 1

m13*m14*0.1

nodelay

--

true

0

false

PMID: 9917870, 8376546 LPS, IL-1beta and TNF-alpha induce IL-1beta and IL-6 production in brain microvessel endothelial cells and smooth muscle/pericytes invitro.

Go back
941.0, 841.0
30.0, 30.0

p10

p10

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e19 e14

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c34 : 1
stoichiometry:c26 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 9917870, 1539653 The microinjection into the OVLT region of the COX inhibitor indomethacin abrogates the rise in intra-OVLT (and intra-POA) PGE2 levels induced by iv IL-1beta.

Go back
577.0, 1085.0
30.0, 30.0

p11

p11

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e20 e5

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c31 : 1
stoichiometry:c30 : 1

m20*m5*0.1

nodelay

--

true

0

false

PMID: 9917870, 8835720, 8593576 c-fos and COX-2 are induced in microglia along blood vessels in the OVLT region and its adjacent meninges after iv LPS.

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549.0, 605.0
30.0, 30.0

p12

p12

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e5

e23

true true true true

--

and

mass

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

m5*0.1

nodelay

--

true

0

false

PMID: 9917870, 7864854 Although Kc synthesize IL-1 mRNA in vitro within 30 minutes after LPS treatment , they apparently are unable to secret its biologically active, mature form.

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625.0, 853.0
30.0, 30.0

p13

p13

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e14

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c35 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 9917870, 7914071 PGE1EP1 receptors are reportedly upregulated in the OVLT region after iv IL-1beta.

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457.0, 689.0
30.0, 30.0

p14

p14

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e5

e24

true true true true

--

and

mass

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

m5*0.1

nodelay

--

true

0

false

PMID: 99178790, 8027674, 7957239 In fact, LPS and IL-1beta stimulate the increased production of CPLA2 after some hours by inducing post-transcriptional modifications and de novo synthesis.

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437.0, 761.0
30.0, 30.0

p15

p15

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e14

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c39 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 99178790, 8027674, 7957239 In fact, LPS and IL-1beta stimulate the increased production of CPLA2 after some hours by inducing post-transcriptional modifications and de novo synthesis.

Go back
821.0, 253.0
30.0, 30.0

p16

p16

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e47

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c82 : 1

m47*0.1

nodelay

--

true

0

false

PMID: 9917870 These cells (Kc) are thereby stimulated to quickly release one or more mediators (that may include PGE2) which, in turn bind to their receptors on nearby terminals of hepatic vagal branches.

Go back
909.0, 249.0
30.0, 30.0

p17

p17

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e5 e27

e28

true true true true

--

and

mass

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

m5*m27*0.1

nodelay

--

true

0

false

PMID: 9917870 However, LPS induced synthesis of PGE2 by macrophages is considerabloe delayed relative to its prompt appearance in blood , due to the slow activation by LPS of the cPLA2 that triggers the releaseof arachidonic acid from membrane phospholipids , on the one hand and the induction of COX-2 that selectively mediates the conversion of archidonic acid liberated in response to LPS into PGE2, on the ohter, as reviewed earlier.

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197.0, 353.0
30.0, 30.0

p14

p18

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

e24

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c81 : 1
stoichiometry:c86 : 1

m24*0.1

nodelay

--

true

0

false

PMID: 99178790, 8027674, 7957239 In fact, LPS and IL-1beta stimulate the increased production of CPLA2 after some hours by inducing post-transcriptional modifications and de novo synthesis.

Go back
825.0, 861.0
30.0, 30.0

p19

p19

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e16 e5

e17

true true true true

--

and

mass

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

m16*m5*0.1

nodelay

--

true

0

false

PMID: 9917870 However, LPS induced synthesis of PGE2 by macrophages is considerabloe delayed relative to its prompt appearance in blood , due to the slow activation by LPS of the cPLA2 that triggers the releaseof arachidonic acid from membrane phospholipids , on the one hand and the induction of COX-2 that selectively mediates the conversion of archidonic acid liberated in response to LPS into PGE2, on the ohter, as reviewed earlier.

Go back
673.0, 337.0
30.0, 30.0

p2

p2

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

e12

e14

true true true true

--

and

mass

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

m12*0.1

nodelay

--

true

0

false

PMID: 9917870, 8376546 LPS, IL-1beta and TNF-alpha induce IL-1beta and IL-6 production in brain microvessel endothelial cells and smooth muscle/pericytes invitro.

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533.0, 213.0
30.0, 30.0

p20

p20

cso30:i:ME_MetabolicReaction

cso30:i:CC_Cytosol

--

e17 e30

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c40 : 1
stoichiometry:c51 : 1

m17*m30*0.1

nodelay

--

true

0

false

PMID: 9917870 However, LPS induced synthesis of PGE2 by macrophages is considerabloe delayed relative to its prompt appearance in blood , due to the slow activation by LPS of the cPLA2 that triggers the releaseof arachidonic acid from membrane phospholipids , on the one hand and the induction of COX-2 that selectively mediates the conversion of archidonic acid liberated in response to LPS into PGE2, on the ohter, as reviewed earlier.

Go back
893.0, 1161.0
30.0, 30.0

p21

p21

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e31

e18

true true true true

--

and

mass

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

m31*0.1

nodelay

--

true

0

false

PMID: 9917870, 8244278 C3a dose dependently stimulates PGE2 production by Kc within 2 minutes.

Go back
885.0, 1221.0
30.0, 30.0

p22

p22

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e43

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c59 : 1

m43*0.1

nodelay

--

true

0

false

PMID: 9917870, 6432907 C5a and C5b-9 also potently stimulate macrophage PGE2 synthesis.

Go back
881.0, 1301.0
30.0, 30.0

p23

p23

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e42

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c60 : 1

m42*0.1

nodelay

--

true

0

false

PMID: 9917870, 6432907 C5a and C5b-9 also potently stimulate macrophage PGE2 synthesis.

Go back
425.0, 229.0
30.0, 30.0

p24

p24

cso30:i:ME_MetabolicReaction

cso30:i:CC_Cytosol

--

e30 e38

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c73 : 1
stoichiometry:c75 : 1
stoichiometry:c74 : 1

m30*m38*0.1

nodelay

--

true

0

false

PMID: 9917870 The subsequent conversion of this arachidonic acid to PGE2 is catalyzed by constitutive COX-1.

Go back
505.0, 285.0
30.0, 30.0

p25

p25

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e12 e5 e18

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c63 : 1
stoichiometry:c64 : 1
stoichiometry:c62 : 1

m12*m5*0.1

nodelay

--

true

0

false

PMID: 9917870, 3148653 PGE2 inhibits the LPS induced synthesis of Il-1beta and TNF-alpha in Kuppfer cells

Go back
409.0, 1061.0
30.0, 30.0

p26

p26

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e34 e5 e18

e35

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c65 : 1
stoichiometry:c67 : 1
stoichiometry:c68 : 1
stoichiometry:c66 : 1

m34*m5*0.1

nodelay

--

true

0

false

PMID: 9917870, 3148653 PGE2 inhibits the LPS induced synthesis of Il-1beta and TNF-alpha in Kuppfer cells

Go back
305.0, 433.0
30.0, 30.0

p27

p27

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e5

e36

true true true true

--

and

mass

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

m5*0.1

nodelay

--

true

0

false

PMID: 9917870 EP3 mRNA was recently found to be induced in the mouse in the nodose ganglion by systemis LPS and IL-1beta

Go back
329.0, 501.0
30.0, 30.0

p28

p28

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e14

e36

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c72 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 9917870 EP3 mRNA was recently found to be induced in the mouse in the nodose ganglion by systemis LPS and IL-1beta

Go back
789.0, 917.0
30.0, 30.0

p29

p29

cso30:i:ME_Hydrolysis

cso30:i:CC_Cytosol

--

e37 e39

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c78 : 1
stoichiometry:c77 : 1

m37*m39*0.1

nodelay

--

true

0

false

PMID: 9917870 PGE2 under these conditions could be generated indirectly through the hydrolysis of membrane associated phosphoinositide (PI) by PI-specific phospholipase C (PI-PLC).

Go back
609.0, 53.0
30.0, 30.0

p20

p3

cso30:i:ME_MetabolicReaction

cso30:i:CC_Cytosol

--

e29 e28

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c5 : 1
stoichiometry:c9 : 1
stoichiometry:c7 : 1

m29*m28*0.1

nodelay

--

true

0

false

PMID: 9917870 However, LPS induced synthesis of PGE2 by macrophages is considerabloe delayed relative to its prompt appearance in blood , due to the slow activation by LPS of the cPLA2 that triggers the releaseof arachidonic acid from membrane phospholipids , on the one hand and the induction of COX-2 that selectively mediates the conversion of archidonic acid liberated in response to LPS into PGE2, on the ohter, as reviewed earlier.

Go back
717.0, 1273.0
30.0, 30.0

p30

p30

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e40 e33

e39

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c79 : 1
stoichiometry:c25 : 1
stoichiometry:c80 : 1

m40*m33*0.1

nodelay

--

true

0

false

PMID: 9917870 PI-PLC is activated by C.

Go back
1213.0, 225.0
30.0, 30.0

p31

p31

cso30:i:ME_UnknownActivation

cso30:i:CC_Extracellular

--

e5 e33

e44

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c83 : 1
stoichiometry:c84 : 1
stoichiometry:c85 : 1

m5*m33*0.1

nodelay

--

true

0

false

PMID: 9917870 Our working hypothesis, therefore is that a single iv injection of a low , pyrogenic dose (2 microgram/kg) of LPS into concious guinea pigs activates C, generating C components that bind to their receptors on Kupffer cells (Kc).

Go back
1165.0, 65.0
30.0, 30.0

p32

p32

cso30:i:ME_UnknownProduction

cso30:i:CC_Extracellular

--

e44

e45

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c87 : 1

m44*0.1

nodelay

--

true

0

false

PMID: 9917870 Our working hypothesis, therefore is that a single iv injection of a low , pyrogenic dose (2 microgram/kg) of LPS into concious guinea pigs activates C, generating C components that bind to their receptors on Kupffer cells (Kc).

Go back
1073.0, 77.0
30.0, 30.0

p33

p33

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e46 e45

e47

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c88 : 1
stoichiometry:c89 : 1
stoichiometry:c90 : 1

m46*m45*0.1

nodelay

--

true

0

false

PMID: 9917870 Our working hypothesis, therefore is that a single iv injection of a low , pyrogenic dose (2 microgram/kg) of LPS into concious guinea pigs activates C, generating C components that bind to their receptors on Kupffer cells (Kc).

Go back
341.0, 557.0
30.0, 30.0

p34

p34

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e18

e25

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c54 : 1

m18*0.1

nodelay

--

true

0

false

PMID: 9917870 Circulating LPS, IL-1beta and PGE2 induce c-fos, IL-1RI and PGE2EP3 receptor expression respectively in the nodose ganglion.

Go back
881.0, 1093.0
30.0, 30.0

p35

p35

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e18 e48

e49

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c94 : 1
stoichiometry:c95 : 1

m18*m48*0.1

nodelay

--

true

0

false

PMID: 9917870 These cells (Kc) are thereby stimulated to quickly release one or more mediators (that may include PGE2) which, in turn bind to their receptors on nearby terminals of hepatic vagal branches.

Go back
345.0, 613.0
30.0, 30.0

p36

p36

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e5

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c92 : 1
stoichiometry:c98 : 1

m5*0.1

nodelay

--

true

0

false

PMID: 9917870 Circulating LPS, IL-1beta and PGE2 induce c-fos, IL-1RI and PGE2EP3 receptor expression respectively in the nodose ganglion.

Go back
337.0, 669.0
30.0, 30.0

p37

p37

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e14

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c99 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 9917870 Circulating LPS, IL-1beta and PGE2 induce c-fos, IL-1RI and PGE2EP3 receptor expression respectively in the nodose ganglion.

Go back
317.0, 729.0
30.0, 30.0

p38

p38

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e18

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c100 : 1

m18*0.1

nodelay

--

true

0

false

PMID: 9917870 Circulating LPS, IL-1beta and PGE2 induce c-fos, IL-1RI and PGE2EP3 receptor expression respectively in the nodose ganglion.

Go back
509.0, 913.0
30.0, 30.0

p39

p39

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e14

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c20 : 1
stoichiometry:c105 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 9917870 Circulating LPS, IL-1beta and PGE2 induce c-fos, IL-1RI and PGE2EP3 receptor expression respectively in the nodose ganglion.

Go back
725.0, 373.0
30.0, 30.0

p4

p4

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e12 e35

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c6 : 1
stoichiometry:c91 : 1
stoichiometry:c8 : 1

m12*m35*0.1

nodelay

--

true

0

false

PMID: 9917870, 8376546 LPS, IL-1beta and TNF-alpha induce IL-1beta and IL-6 production in brain microvessel endothelial cells and smooth muscle/pericytes invitro.

Go back
465.0, 865.0
30.0, 30.0

p40

p40

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleolus

--

e5

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c101 : 1
stoichiometry:c104 : 1

m5*0.1

nodelay

--

true

0

false

PMID: 9917870 Circulating LPS, IL-1beta and PGE2 induce c-fos, IL-1RI and PGE2EP3 receptor expression respectively in the nodose ganglion.

Go back
529.0, 965.0
30.0, 30.0

p41

p41

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e18

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c106 : 1

m18*0.1

nodelay

--

true

0

false

PMID: 9917870 Circulating LPS, IL-1beta and PGE2 induce c-fos, IL-1RI and PGE2EP3 receptor expression respectively in the nodose ganglion.

Go back
869.0, 389.0
30.0, 30.0

p5

p5

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e13 e5

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c16 : 1
stoichiometry:c14 : 1

m13*m5*0.1

nodelay

--

true

0

false

PMID: 9917870, 8376546 LPS, IL-1beta and TNF-alpha induce IL-1beta and IL-6 production in brain microvessel endothelial cells and smooth muscle/pericytes invitro.

Go back
857.0, 605.0
30.0, 30.0

p6

p6

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e13 e35

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c97 : 1
stoichiometry:c15 : 1

m13*m35*0.1

nodelay

--

true

0

false

PMID: 9917870, 8376546 LPS, IL-1beta and TNF-alpha induce IL-1beta and IL-6 production in brain microvessel endothelial cells and smooth muscle/pericytes invitro.

Go back
565.0, 669.0
30.0, 30.0

p7

p7

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e5

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c21 : 1

m5*0.1

nodelay

--

true

0

false

PMID: 9917870, 9227582, 8724976, 8593576, 8891309 LPS or IL-beta injected iv or intraperitoneally (ip) induces cyclooxygenase-2 (COX-2) mRNA in cerebral blood vessels.

Go back
673.0, 649.0
30.0, 30.0

p8

p8

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e14

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c22 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 9917870, 9227582, 8724976, 8593576, 8891309 LPS or IL-beta injected iv or intraperitoneally (ip) induces cyclooxygenase-2 (COX-2) mRNA in cerebral blood vessels.

Go back
953.0, 661.0
30.0, 30.0

p9

p9

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e16

e17

true true true true

--

and

mass

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

m16*0.1

nodelay

--

true

0

false

PMID: 9917870, 8835720, 8593576 c-fos and COX-2 are induced in microglia along blood vessels in the OVLT region and its adjacent meninges after iv LPS.

Go back
470.0, 363.56358858271415

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
370.1540140564662, 263.0

c10

c10

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
281.145770236779, 701.1214751973158

c100

c100

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
501.06188776033247, 321.0

c101

c101

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
425.8248474318787, 883.0

c104

c104

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
425.83112666104313, 907.6350704017563

c105

c105

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
425.1165361451483, 918.6544374799411

c106

c106

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
365.5176300967837, 263.0

c11

c11

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
486.0, 412.7982623162974

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
486.0, 568.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
891.0, 419.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
882.0, 537.7116902962213

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
906.5044337701482, 316.0

c16

c16

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
463.6120680655489, 263.0

c17

c17

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
726.0, 263.0

c18

c18

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
601.6583344764729, 321.0

c19

c19

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
486.0, 537.588372732867

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
530.2227420862016, 263.0

c20

c20

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
549.0081344481972, 699.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
566.2038708836149, 676.0

c22

c22

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
570.0, 681.945051918366

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
934.3104235544095, 691.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
754.1662062457268, 169.0

c25

c25

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
767.817006370697, 870.0

c26

c26

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
874.0, 874.4746418390049

c28

c28

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
404.0, 916.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
693.0, 270.66829085023244

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
607.0, 1105.0

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
606.5773184358047, 321.0

c31

c31

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
586.0429341297659, 320.0

c32

c32

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
473.94256100321184, 622.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
726.0, 263.0

c34

c34

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
601.6136689420844, 855.456022239382

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
493.89324018399793, 321.0

c36

c36

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
689.6198922686413, 263.0

c37

c37

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
360.4074572589928, 715.0

c38

c38

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
369.72987951680994, 780.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
855.0, 521.5689290811055

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
558.4927846909883, 145.0

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1202.243671487671, 58.0

c41

c41

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
946.8479448413955, 268.55234073785846

c42

c42

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
868.0, 195.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
799.5295573660936, 219.70291802885413

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
566.4766657537489, 988.8459566417496

c45

c45

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
353.377481273083, 759.8298791508148

c46

c46

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
857.5226176211019, 159.0

c47

c47

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
570.0, 793.0

c48

c48

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
853.0, 804.1218086994555

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
646.6069714518937, 49.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
851.774871226771, 321.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
552.0, 243.0

c51

c51

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
373.0009290976896, 593.2442540114798

c52

c52

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
562.4790981167798, 249.6285503739701

c53

c53

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
301.9711840576478, 573.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
930.9235580841554, 1179.103280239566

c55

c55

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
773.4610074998332, 1077.7175610316242

c56

c56

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
922.8629774954745, 1240.4743082804014

c57

c57

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
918.8662560398757, 1320.4567140814584

c58

c58

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
764.2332154634527, 1079.0509053796172

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
470.0, 394.2573305919324

c6

c6

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
758.0309682041927, 1079.9102312071875

c60

c60

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
447.0, 322.2812111366993

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
535.0, 256.019375177176

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
542.9992546091923, 300.1092048410811

c63

c63

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
525.1386973557081, 318.83449714201265

c64

c64

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
308.0, 924.0

c65

c65

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
434.0, 1091.0

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
443.4725781646625, 321.0

c67

c67

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
442.992378860917, 1058.0

c68

c68

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
342.8878724826217, 312.0

c69

c69

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
607.3688904516371, 83.0

c7

c7

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
262.19728960114014, 460.0

c70

c70

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
643.0220638422984, 263.0

c71

c71

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
274.0, 516.0

c72

c72

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
461.41301980074445, 145.0

c73

c73

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
446.0, 259.0

c74

c74

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
394.0, 159.0

c75

c75

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
826.9598003187556, 915.0

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
602.0063046869977, 152.74433609181128

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
781.0, 954.971513821526

c78

c78

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
664.0, 1265.0

c79

c79

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
723.1515187657129, 270.91669151427607

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
743.0, 1247.4

c80

c80

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
218.11291961661345, 390.7159296713831

c81

c81

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
746.9249715859131, 283.0

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1160.0, 257.04032685494076

c83

c83

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1243.6499055497527, 169.0

c84

c84

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1230.0, 68.9573629295819

c85

c85

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
211.66092522274096, 179.6231673315287

c86

c86

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1164.809037657595, 95.0

c87

c87

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1008.0, 60.0

c88

c88

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1108.591463582408, 112.7214976192082

c89

c89

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
644.7317695048383, 88.5809334652373

c9

c9

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1026.6177335302002, 102.0

c90

c90

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
505.0, 410.64930868163793

c91

c91

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
382.4050079594391, 317.0

c92

c92

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
774.0, 1066.0

c93

c93

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
916.7726572183574, 1023.0

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
911.0, 1108.0

c95

c95

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
515.0, 641.6583678516108

c97

c97

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
293.13108104165445, 635.0

c98

c98

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
293.99385560585233, 681.3134845335628

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back