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com.apple.print.PrintSettings.PMFirstPage com.apple.print.ticket.creator com.apple.printingmanager com.apple.print.ticket.itemArray com.apple.print.PrintSettings.PMFirstPage 1 com.apple.print.ticket.client com.apple.printingmanager com.apple.print.ticket.modDate 2003-03-09T23:47:12Z com.apple.print.ticket.stateFlag 0 com.apple.print.PrintSettings.PMLastPage com.apple.print.ticket.creator com.apple.printingmanager com.apple.print.ticket.itemArray com.apple.print.PrintSettings.PMLastPage 2147483647 com.apple.print.ticket.client com.apple.printingmanager com.apple.print.ticket.modDate 2003-03-09T23:47:12Z com.apple.print.ticket.stateFlag 0 com.apple.print.PrintSettings.PMPageRange com.apple.print.ticket.creator com.apple.printingmanager com.apple.print.ticket.itemArray com.apple.print.PrintSettings.PMPageRange 1 2147483647 com.apple.print.ticket.client com.apple.printingmanager com.apple.print.ticket.modDate 2003-03-09T23:47:12Z com.apple.print.ticket.stateFlag 0 com.apple.print.ticket.APIVersion 00.20 com.apple.print.ticket.privateLock com.apple.print.ticket.type com.apple.print.PrintSettingsTicket ^Graph*@@?ێ88?ڪ %WDashSettings#  !0#Normal@ Geneva<HHHH$$0#Normal@ Geneva<HHHH$$4444440 oTqNormal@ Geneva<HHHH$$4 4 4 4 4 4 0homeddA 7Integrin:Users:davidmorgan:DLMDocs:Teaching:IgorWeb:IgorSite:ECE4084:Integrin7H+A VECE4084A W IgorSiteW(pA VA O j > |bDIntegrin:Users:davidmorgan:DLMDocs:Teaching:IgorWeb:IgorSite:ECE4084ECE4084Integrin;Users/davidmorgan/DLMDocs/Teaching/IgorWeb/IgorSite/ECE4084/RecentWindowsAdvanced Topics.ihfAnalysis.ihfDialog Help.ihfDistributionErrors.ihfGetting Started.ihfGraphics.ihfHelp BrowserIgor Reference.ihfInstructionsPowersProgramming.ihfProgressPVrate constants 4Misc_EndXOPState_StartData Browsering.ihfiGizmoP % DistributionErXLLoadWave@ Started.ihfGraSurface PlotterrowserIgor RefeInterpolatectionsPowers4XOPState_End\ 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(Progress in Biophysics and Biophysical Chemistry, vol 7, p255-318)  fThe rate constant curves are set from Huxley's fitted variables in the Rate Constants window. "f" is the rate constant for attachment, and "g" is the rate constant for detachment. f is g1*x for x between zero and h, and zero elsewhere. g is g1*x for x>0 and g2 for x<0. The basic equation then is dn/dt=f*(1-n)-g*n, where n is a function of x, representing the probability of cross-bridges with a distortion x being attached. A menu item in Macros sets these to Huxley's values. Other functions can be entered from the command line, and will only be overwritten if the parameters in the Rate Constants window are changed. Another Macro modifies the detachment rate constant for large crossbridge extensions, to reduce tension during stretch, which is higher in the Huuxley model than in real muscle. This has no effect on isometric or shortening performance.  The progress window is the main controller. The Go button causes the simulation to run up to the "Stop at" time. You can then change the conditions, increment "Stop at" and resume the simulation. The tension variable is used only for Isotonic contractions, and the velocity variable for isokinetic contractions. Reset can set the attachment distribution to zero (relaxed) or to the steady sate isometric distribution.  "Power out" is the mechanical work done by the muscle. "Power in" is the rate of detachment of crossbridges, scaled to match the power out units. (Detachment is used rather than attachment because it better fits the biochemistry of crossbridge cycling.)  The units here are all arbitrary. To get real units would require scaling by the number of half sarcomeres in series and the number of crossbridges in the cross-section and their stiffness. Hence all lengths are in terms of h, the maximum reach of the crossbridge. Force units are defined by a unit crossbridge stiffness, that is a crossbridge with extension of 1 unit of h will produce unit force. Time is in seconds as the rate constants are per sec. Work units come from the definition of work as force times distance, each in their units. Power is work per sec. The ratio of chemical energy to mechanical work is set by the constant w/e, which must be less than unity.Z"*JR X `Geneva d TEXTIGR0"dWindowsWindows#pragma rtGlobals=1 // Use modern global access method. Window RateConsts() : Graph PauseUpdate; Silent 1 // building window... Display /W=(5,42,400,250) f,g as "rate constants" Modify lStyle(f)=1,lStyle(g)=3 Label bottom "x (h)" Legend/J /A=MC/X=4.50161/Y=23.5669 "\s(f) f\r\s(g) g" EndMacro Window Distribution() : Graph PauseUpdate; Silent 1 // building window... Display /W=(244,62,639,270) n as "Distribution" Modify mode=4 Modify marker=19 Modify msize=1 SetAxis left 0,1 EndMacro Window progress() : Graph PauseUpdate; Silent 1 // building window... Display /W=(11,50,514,320) tension,stiffness vs times as "Progress" Append /R length vs times Modify marker(stiffness)=8,marker(length)=13 Modify lStyle(stiffness)=1,lStyle(length)=3 Modify msize=2 Label left "Tension, Stiffness" Label bottom "Time" Label right "Length change (h/hs)" SetAxis left 0,1 Legend/J /A=MC/X=-24.8344/Y=30.9677 "\s(tension) tension\r\s(stiffness) stiffness" AppendText "\s(length) length" EndMacro Window Tesion_contributions() : Graph PauseUpdate; Silent 1 // building window... Display /W=(5,42,400,250) nx EndMacro Window Progress_Table() : Table PauseUpdate; Silent 1 // building window... Edit /W=(5,42,432,251) tension.y,stiffness.y,times.y,length.y Modify width(Point)=64 EndMacro RH Geneva,S9xHH(Fg(HH(dh FHHHH$$ RRMPSRWMT1*1dL1X1\|// Platform=Macintosh, IGORVersion=6.020, architecture=PowerPC Silent 101 // use | as bitwise or -- not comment. DefaultFont "Geneva" OpenProc/W=(5,44,505,339)/J=182273/V=0 "Windows" MoveWindow/P 340,111,881,652 MoveWindow/C 14,547,508,691 OpenNotebook/N=Notebook0/W=(331,222,831,517)/J=178692 "Instructions" as "Instructions" RateConsts() Distribution() Tension_contributions() progress() PV_1() Powers() Window Powers() : Graph PauseUpdate; Silent 1 // building window... Display /W=(13,339,504,526) PowerOut vs times as "Powers" AppendToGraph PowerIn vs times ModifyGraph rgb(PowerIn)=(0,0,65535) Cursor/P A PowerIn 1418 ShowInfo Legend/C/N=text0/J/F=0/A=MC/X=-31.65/Y=-7.25 "\\s(PowerOut) OutputPower(Mech)\r\\s(PowerIn) InputPower(Chem)" EndMacro Window PV_1() : Graph PauseUpdate; Silent 1 // building window... String fldrSav0= GetDataFolder(1) SetDataFolder root:PV: Display /W=(463,107,833,704) TenPV,EffPV vs VelPV as "PV" AppendToGraph/R POutPV vs VelPV AppendToGraph/R PInPV vs VelPV SetDataFolder fldrSav0 ModifyGraph mode=3 ModifyGraph marker(TenPV)=19,marker(EffPV)=19,marker(POutPV)=17,marker(PInPV)=17 ModifyGraph rgb(EffPV)=(65535,0,52428),rgb(POutPV)=(1,52428,26586),rgb(PInPV)=(65535,43690,0) ModifyGraph grid(bottom)=1 Label left "Tension\\s(TenPV), Efficiency\\s(EffPV)" Label bottom "Velocity (Lengthening)" Label right "Power In\\s(PInPV), Out\\s(POutPV)" SetAxis/A/N=1 left SetAxis/A/N=1 right ControlBar 25 Button Clear,pos={4,2},size={50,20},proc=ClearPV,title="Clear" Button Add,pos={64,2},size={131,20},proc=AddPV,title="Add current time" EndMacro Window progress() : Graph PauseUpdate; Silent 1 // building window... Display /W=(14,44,543,316) tension,stiffness vs times as "Progress" AppendToGraph/R length vs times ModifyGraph marker(stiffness)=8,marker(length)=13 ModifyGraph lStyle(stiffness)=1,lStyle(length)=3 ModifyGraph rgb(stiffness)=(3,52428,1),rgb(length)=(0,0,65535) ModifyGraph msize=2 Label left "Tension, Stiffness" Label bottom "Time" Label right "Length change (h/hs)" Cursor/P A length 10 Legend/C/N=text0/J/A=MC/X=-34.16/Y=39.12 "\\s(tension) tension\r\\s(stiffness) stiffness\r\\s(length) length" ControlBar 25 PopupMenu reset,pos={7,1},size={59,20},proc=Reset,title="Reset" PopupMenu reset,mode=0,value= #"\"Relaxed;Isometric\"" PopupMenu State,pos={71,1},size={107,20},proc=SetState,title="State" PopupMenu State,mode=2,popvalue="Isokinetic",value= #"\"Isometric;Isokinetic;Isotonic\"" SetVariable StopT,pos={389,5},size={80,15},title="Stop at" SetVariable StopT,limits={-inf,inf,0.1},value= StopT Button Go,pos={472,2},size={50,20},proc=Go,title="Go" SetVariable Velocity,pos={181,5},size={122,15},title="Velocity(h/hs/s)" SetVariable Velocity,help={"Units of h per half-sarcomere per second"} SetVariable Velocity,value= Velocity SetVariable IsoTen,pos={306,5},size={80,15},title="Tension" SetVariable IsoTen,help={"Units of h per half-sarcomere per second"} SetVariable IsoTen,limits={-inf,inf,0.05},value= IsoTen EndMacro Window Tension_contributions() : Graph PauseUpdate; Silent 1 // building window... Display /W=(544,419,971,574) nx as "Tension Contributions:nx" Cursor/P A nx 293 EndMacro Window Distribution() : Graph PauseUpdate; Silent 1 // building window... Display /W=(546,245,969,396) n as "Distribution" ModifyGraph mode=4 ModifyGraph marker=19 ModifyGraph msize=1 Label left "Probability of attachment" SetAxis left 0,1 EndMacro Window RateConsts() : Graph PauseUpdate; Silent 1 // building window... Display /W=(547,44,970,220) f,g as "rate constants" ModifyGraph lStyle(f)=1,lStyle(g)=3 Label left "Rates (/s)" Label bottom "x (h)" Legend/C/N=text0/J/A=MC/X=4.50/Y=23.57 "\\s(f) f\r\\s(g) g" ControlBar 25 SetVariable setvar0,pos={6,4},size={120,15},proc=SetRates,title="g1/(f1+g1)" SetVariable setvar0,limits={0.02,10,0.02},value= g1overf1plusg1 SetVariable g1,pos={132,4},size={62,15},proc=SetRates,title="g1",value= g1 SetVariable g2over,pos={202,4},size={120,15},proc=SetRates,title="g2/(f1+g1)" SetVariable g2over,value= g2overf1plusg1 SetVariable setvar1,pos={332,4},size={89,15},proc=SetRates,title="w/e" SetVariable setvar1,value= wovere EndMacro $//Set of macros to simulate the original Huxley model. //Generates stiffness as well as force //All lengths are in units of Huxley's h //Energetics added Macro SetHuxleyRates() g1overf1plusg1=0.1875 g1=10 g2overf1plusg1=3.91 wovere=0.75 //Only used for energetics SetRates("",0,"","") //Call SetVariableControl to generate rates as finctions of x End Macro IncreaseDetachmentAtLargex() //Modifies the detachment rate constant for large crossbridge extensions, to reduce tension during stretch //Has no effect on isometric or shortening performance g=g+200*(x-2)*(x>2) End Macro ShowForceVelocity() PV() //Below End Function SetRates(ctrlName,varNum,varStr,varName) : SetVariableControl String ctrlName Variable varNum String varStr String varName WAVE f,g NVAR f1, g1, g2, g1overf1plusg1, g2overf1plusg1 f1=g1*(1-g1overf1plusg1)/g1overf1plusg1 g2=g2overf1plusg1*(f1+g1) make /o /n=301 /o n=0, nx=0,dndt,tempn,f,g //Set resolution of distribution waves SetScale x -2,4,"h", n,nx,dndt,tempn,f,g //Set range of distribution waves f=f1*x*(x>0)*(x<=1) //Attachment rate constant g=g2*(x<0)+g1*x*(x>0) //Detachment rate constant End Function SetState(ctrlName,popNum,popStr) : PopupMenuControl String ctrlName //From State menu Variable popNum String popStr NVAR State State=popnum //1 for Isometric, 2 for Isokinetic, 3 for Isotonic End Function Reset(ctrlName,popNum,popStr) : PopupMenuControl String ctrlName Variable popNum String popStr WAVE Tension, Stiffness, Times, Length, PowerIn, PowerOut //Output waves WAVE n //distribution of attached bridges NVAR PntNum //Global counter for output waves tension=0;stiffness=0;times=NaN;length=0;PowerIn=0; PowerOut=0 pntnum=0 Times[0]=0 If(Popnum==1) //relaxed n=0 //All bridges detached. Print "Reset to all bridges detached" Else //Isometric NVAR f1,g1 n=(f1/(f1+g1))*(x>0)*(x<=1) //Solution for steady state FindTenStif() //Get moments from distribution Print "Reset to the steady state isometric condition" EndIf End Function Go(ctrlName) : ButtonControl String ctrlName WAVE n, Times WAVE Tension, Length, PowerOut NVAR PntNum, StopT, State Variable PlotInterval, Overflow //Time interval per plotted point switch(State) case 1: // Isometric PlotInterval=0.01 //Suitable value for Huxley parameters Print "Isometric till",StopT do If ((Times[PntNum]+PlotInterval)-StopT>0) //If proposed time step overshoots stop time.... PlotInterval=StopT-Times[PntNum] +0.0001 //...reduce interval EndIf IncPntNum(PlotInterval) //Increment the output wave counter and time and check for overflow Timelapse(PlotInterval) //Let distribution evolve length[pntnum]=length[pntnum-1] //Preserve length. units of h PowerOut[pntnum]=0 // No work done in isometric FindTenStif() //Get moments from distribution DoUpdate //Redraw graphs while ((Times[PntNum]0.01) //If very slow, including zero... PlotInterval=0.01 //Keep interval reasonable EndIf Print "isokinetic with velocity of ",Velocity, "h/hs/s till",StopT do If ((Times[PntNum]+PlotInterval)-StopT>0) //If proposed time step overshoots stop time.... PlotInterval=StopT-Times[PntNum] +0.0001 //...reduce interval EndIf IncPntNum(PlotInterval) //Increment the output wave counter and time and check for overflow Shiftx(Velocity*PlotInterval) //Shift the distribution,usually by 1 timelapse(PlotInterval) //Let distribution evolve FindTenStif() //Get tension and stiffness from new distribution PowerOut[pntnum]=-Tension[pntnum]*Velocity //mechanical power output DoUpdate //Update plots while ((Times[PntNum]0) //Remove any negative values from overshooting dettachment Step+=1 //Next substep while(Step<(steps+.5)) PowerIn[PntNum]=DetachRate/WoverE //Convert detachments to units of work end Function IncPntNum(PlotInterval) //Increment point counter for output waves Variable PlotInterval NVAR PntNum, StopT WAVE Times If(PntNum<(numpnts(Times)-1)) //Room for more points PntNum=PntNum+1 times[pntnum]=times[pntnum-1]+PlotInterval //Increment time Else DoAlert 0, "You have exceeded the allowable record length. Please take any measurements that you need from the windows, and then do a reset before continuing" Times[pntNum]=StopT+0.1 EndIf End Function FindTenStif() WAVE n, nx, tempn //Distribution waves WAVE Tension, Stiffness , PowerIn //Recording waves NVAR PntNum //PntNum is a global variable so that it persists beyonf the end of a timeinterval nx=n*x Integrate nx tension[pntnum]=nx[numpnts(n)]-nx[0] //Units of kh per myosin head tempn=n integrate Tempn stiffness[pntnum]=Tempn[numpnts(n)]-Tempn[0] //units of k per myosin End Function Shiftx(dx) //Shift distribution. dx in units of h Variable dx //Distance to shift distribution, +ve to right WAVE n, TempN WAVE Length, Tension, PowerOut NVAR PntNum //Global counter for output waves TempN=n //Need to store in TempN to avoid zeros on right shift n=Tempn(x-dx) length[pntnum]=length[pntnum-1]+dx //Update length. units of h End // Procedures for PV window of tension, ower and efficiency as functions of velocity Function ClearPV(ctrlName) : ButtonControl //Clear the saved waves String ctrlName WAVE VelPV=root:PV:VelPV,TenPV=root:PV:TenPV,POutPV=root:PV:PoutPV,EffPV=root:PV:EffPV,PInPV=root:PV:PInPV VelPV=0; TenPV=Nan;POutPV=NaN; PInPV=NaN; EffPV=NaN; POutPV=NaN NVAR PVPnt=root:PV:PVPntNum PVPnt=-1 End Function AddPV(ctrlName) : ButtonControl //Keep the current time point as a PV ppoint String ctrlName WAVE VelPV=root:PV:VelPV,TenPV=root:PV:TenPV,POutPV=root:PV:PoutPV,EffPV=root:PV:EffPV, PInPV=root:PV:PInPV WAVE Times, Tension, PowerIn, PowerOut, Length NVAR PntNum //Point number in Progress window NVAR PVPnt=root:PV:PVPntNum //Point number on the PV curve PVPnt+=1 TenPV[PVPnt]=Tension[Pntnum] POutPV[PVPnt]=PowerOut[PntNum-1] //Non-integral shifts cause errors in the last point PInPV[PVPnt]=PowerIn[PntNum] EffPV[PVPnt]=PowerOut[PntNum]/PowerIn[PntNum] VelPV[PVPnt]=(Length[PntNum-3]-Length[PntNum-1])/(Times[PntNum-3]-Times[PntNum-1]) End Window PV() : Graph PauseUpdate; Silent 1 // building window... String fldrSav0= GetDataFolder(1) SetDataFolder root:PV: Display /W=(398,88,768,685) TenPV,EffPV vs VelPV as "PV" AppendToGraph/R POutPV vs VelPV AppendToGraph/R PInPV vs VelPV SetDataFolder fldrSav0 ModifyGraph mode=3 ModifyGraph marker(TenPV)=19,marker(EffPV)=19,marker(POutPV)=17,marker(PInPV)=17 ModifyGraph rgb(EffPV)=(65535,0,52428),rgb(POutPV)=(1,52428,26586),rgb(PInPV)=(65535,43690,0) Label left "Tension\\s(TenPV), Efficiency\\s(EffPV)" Label bottom "Velocity (Lengthening)" Label right "Power In\\s(PInPV), Out\\s(POutPV)" SetAxis/A/N=1 left SetAxis/A/N=1 right ControlBar 25 Button Clear,pos={4,2},size={50,20},proc=ClearPV,title="Clear" Button Add,pos={64,2},size={131,20},proc=AddPV,title="Add current time" EndMacro