globals [
  step
  time
  hour
  day
  total-pathogen
  total-macrophage
  total-fibroblast
  total-damage
  total-LPS
  total-pro
  total-anti
  total-collagen
]

breed [pathogen ]
breed [macrophage]
breed [fibroblast]



turtles-own[
     mlife
     plife
     flife
     ]
patches-own [
      LPS
      pro 
      anti
      collagen
      tissue-damage
      ]


to setup
  ca cp ct
  clear-all-plots
  set total-LPS 0
  set total-pro 0
  set total-anti 0
  set total-collagen 0
  
  ask patches [
    set pcolor green
    set LPS 0
    set pro 0
    set anti 0
    set tissue-damage 0
  ]
  
  set-default-shape turtles "circle"
  
  create-custom-macrophage Initial-Macrophage [
    set color blue
    jump random 100
    set heading random 360
    set mlife 50 + random 40
    ]
  create-custom-fibroblast Initial-Fibroblast [
    set color pink
    jump random 100
    set heading random 360
    set flife 80 + random 50
  ]
  create-custom-pathogen Initial-Pathogen [
    set color black
    jump random sqrt Initial-Pathogen   
    set plife 20 + random 10 
  ]
  
end




to pathogen-function
   wiggle  
   if pathogen-growth >  random 100         
    [hatch 1
       [set breed pathogen
        set color black
        set plife 20 + random 10 
      ]
     ]      
     
   set tissue-damage tissue-damage + 2 * ( count pathogen-here ) + pro
   set plife plife - 1
  if ( plife < 0 ) [die]
    
end

to macrophage-function
   wiggle
   if tissue-damage > 0
   [
    set pro pro +  2 * pro_production / (1 + anti)
    set anti anti + 1 * anti_production / (1 + anti)
   ]
   ask pathogen-here [die]
   
    set mlife mlife - 1
    if mlife <= 0 [die]
    mac-LPS-sniff
    mac-pro-sniff
    
   
end

to fibroblast-function
   wiggle
   set anti anti + 1 * anti_production
   set collagen collagen + anti * collagen_production
   set flife flife - 1
   if flife <= 0 [die]
   fib-anti-sniff
end

to tissue-function
    set LPS LPS + LPS_production
    set pro pro + pro_production
    set anti anti + anti_production
    set tissue-damage tissue-damage + total-macrophage
    set tissue-damage tissue-damage - collagen
    
    if tissue-damage < 0 [set tissue-damage 0]
   
end

to go

 set step step + 1
 
  if  ( step mod 4 = 0 )
  [
  ask pathogen 
  [ pathogen-function ]
  ]
  
  ask macrophage
  [macrophage-function]
  ask fibroblast
  [fibroblast-function]
  ask patches
  [ 
   evaporate
  ]
  
  ask patches with [tissue-damage > 0 ]
  [
          tissue-function
            if 5 > random 100
            [
               sprout-macrophage ( 0.5 + ( pro + LPS ) / ( macrophage-sprout * 100 ) ) [ 
               set color blue
               set mlife 50 + random 40
                ]
            ]
            
            
            if 5 > random 100
            [
               sprout-fibroblast ( 0.5 +   anti / ( fibroblast-sprout * 100 ) ) [ 
               set color pink
               set flife 80 + random 50
                ]
            ]
            
  
  ]
  
   diffuse LPS 1
   diffuse pro 1
   diffuse anti 1
   draw-graph
   set-scale-pc
   update-system
end

to wiggle
  rt random 45
  lt random 45
  fd 1
end 
    
    
 to evaporate 
set pro pro * 0.8   
set anti anti * 0.8
set LPS LPS * 0.8
set collagen collagen * 0.99
end 
    
to mac-LPS-sniff
  locals [ahead rig lef]
  set ahead LPS-of patch-ahead 1
  set rig   LPS-of patch-right-and-ahead 90 1
  set lef   LPS-of patch-left-and-ahead 90 1
  ifelse ((rig >= ahead) and (rig >= lef))
    [rt 90
    ]
    [if (lef >= ahead)
       [lt 90]
    ]

end

to mac-pro-sniff
  locals [ahead rig lef]
  set ahead pro-of patch-ahead 1
  set rig   pro-of patch-right-and-ahead 90 1
  set lef   pro-of patch-left-and-ahead 90 1
  ifelse ((rig >= ahead) and (rig >= lef))
    [rt 90
    ]
    [if (lef >= ahead)
       [lt 90]
    ]
end


to fib-anti-sniff
  locals [ahead rig lef]
  set ahead anti-of patch-ahead 1
  set rig   anti-of patch-right-and-ahead 90 1
  set lef   anti-of patch-left-and-ahead 90 1
  ifelse ((rig >= ahead) and (rig >= lef))
    [rt 90
    ]
    [if (lef >= ahead)
       [lt 90]
    ]


end


to set-scale-pc
ask patches 
 [set pcolor scale-color green tissue-damage -50 50]
end

to update-system

  set total-pro sum values-from patches [pro / 1000]
  set total-anti sum values-from patches [anti / 1000]
  set total-LPS sum values-from patches [LPS / 1000]
  set total-damage sum values-from patches [tissue-damage / 1000]
  set total-collagen sum values-from patches [collagen / 1000]
 
end



  
;; draw graph

to draw-graph
 set-current-plot "Pro & antinflammatory"
 set-current-plot-pen "pro"
 plot total-pro
 set-current-plot-pen "anti" 
 plot total-anti
 
 
 
  set-current-plot "Damage"
 set-current-plot-pen "total-damage"
 plot total-damage
 set-current-plot "Pathogen"
 set-current-plot-pen "pathogen"
 plot count pathogen
end
  
  
  to survival
  set Initial-Macrophage 50
  set Initial-Fibroblast 50
  set Initial-Pathogen   90
  set pathogen-growth    11
  set collagen_production  80
  set macrophage-sprout  1.5
  set fibroblast-sprout  2
  set LPS_production    36
  set pro_production    34
  set anti_production   61
 
  end
  
  
  to persistent-infection
  set Initial-Macrophage 50
  set Initial-Fibroblast 50
  set Initial-Pathogen   90
  set pathogen-growth    17
  set collagen_production  51
  set macrophage-sprout  2.5
  set fibroblast-sprout  2.5
  set LPS_production    50
  set pro_production    50
  set anti_production   50
  end
  
  
  to septic-death
  set Initial-Macrophage 50
  set Initial-Fibroblast 50
  set Initial-Pathogen   90
  set pathogen-growth    50
  set collagen_production  50
  set macrophage-sprout  2.5
  set fibroblast-sprout  2.5
  set LPS_production    50
  set pro_production    50
  set anti_production   50
  end
  
  to aseptic-death
  set Initial-Macrophage 50
  set Initial-Fibroblast 50
  set Initial-Pathogen   90
  set pathogen-growth    11
  set collagen_production  51
  set macrophage-sprout  2.5
  set fibroblast-sprout  2.5
  set LPS_production    50
  set pro_production    50
  set anti_production   50
  end
  
  
  
  
  
  
@#$#@#$#@
GRAPHICS-WINDOW
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BUTTON
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MONITOR
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pathogen
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MONITOR
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fibroblast
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Pro & antinflammatory
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NIL
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"anti" 1.0 0 -8630108 true

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SLIDER
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SLIDER
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MONITOR
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PLOT
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Pathogen
NIL
NIL
0.0
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0.0
10.0
true
false
PENS
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BUTTON
4
404
171
437
SURVIVAL
survival
NIL
1
T
OBSERVER
T
NIL

BUTTON
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475
PERSISTENT INFECTION
persistent-infection
NIL
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T
OBSERVER
T
NIL

BUTTON
186
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353
512
SEPTIC DEATH
septic-death
NIL
1
T
OBSERVER
T
NIL

BUTTON
4
479
172
512
ASEPTIC DEATH
aseptic-death
NIL
1
T
OBSERVER
T
NIL

@#$#@#$#@
WHAT IS IT?
-----------
This is a model of the inflammatory response. It implements pathogens, macrophages, and fibroblasts, and the chemicals LPS, collagen, and pro- and anti-inflmmatory cytokines.


HOW IT WORKS
------------
The different types of cells are agents, and the chemicals are patch variables. The patches themselves are the tissue. Inter and Intra-cellular interactions are defined by
the Agent-Based model rules that resemble their biological nature. Different levels are shown in monitors and graphs.

HOW TO USE IT
-------------
After choosing beginning conditions and constants using the sliders, one should press Setup, and then press Go. Go is a continuously running function, and should be pressed again when one wants the model to stop. To reset the model, one needs to press Setup again. 

The different setting buttons (in CAPITALS) preset the sliders to give a situation where that type of consequence would occur.

THINGS TO NOTICE
----------------
The user should notice how the different parts of the model interact, and the various graphs.

THINGS TO TRY
-------------
The user should first try to play around with the first group of sliders (on the top). These change the inital number of different cells. After tries of that, the user can go on to play around with other settings. The sliders are ordered in groups from top to bottom, in the order of the constants that have the largest effect on the model.


EXTENDING THE MODEL
-------------------
The model can be extended to have more exact interactions with the introduction of other chemicals.


NETLOGO FEATURES
----------------
The agent and patch functions of NetLogo really help facilitate an Agent-Based Model. The interactions and intuitively defined in the procedures.


RELATED MODELS
--------------
Gary An's ABMs simulate similar topics wondefully.


CREDITS AND REFERENCES
----------------------
Done by: Yakov Pechersky, Keely Rasmussen, Qi Mi, and Yoram Vodovotz.

Thanks to: Jack Kent Cooke Foundation, University of Pittsburg, Society of Complexity in Acute Illness, Gary An, and many others.
@#$#@#$#@
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@#$#@#$#@
NetLogo 3.1.4
@#$#@#$#@
@#$#@#$#@
@#$#@#$#@
<experiments>
  <experiment name="experiment" repetitions="10" runMetricsEveryTick="true">
    <setup>setup</setup>
    <go>go</go>
    <exitCondition>step &gt; 100</exitCondition>
    <metric>total-damage</metric>
    <enumeratedValueSet variable="Initial-Pathogen">
      <value value="100"/>
    </enumeratedValueSet>
    <enumeratedValueSet variable="fibroblast-sprout">
      <value value="1.5"/>
    </enumeratedValueSet>
    <enumeratedValueSet variable="macrophage-sprout">
      <value value="1.5"/>
    </enumeratedValueSet>
    <enumeratedValueSet variable="pro_production">
      <value value="50"/>
    </enumeratedValueSet>
    <enumeratedValueSet variable="Initial-Fibroblast">
      <value value="41"/>
    </enumeratedValueSet>
    <enumeratedValueSet variable="pathogen-growth">
      <value value="89"/>
    </enumeratedValueSet>
    <enumeratedValueSet variable="anti_production">
      <value value="51"/>
    </enumeratedValueSet>
    <enumeratedValueSet variable="collagen_production">
      <value value="83"/>
    </enumeratedValueSet>
    <enumeratedValueSet variable="LPS_production">
      <value value="50"/>
    </enumeratedValueSet>
    <enumeratedValueSet variable="Initial-Macrophage">
      <value value="45"/>
    </enumeratedValueSet>
  </experiment>
</experiments>
@#$#@#$#@