Honors Course in Classical Civilization
Honors Course in Classical Civilization CLASSIC H195
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Actor Networks Edward A Lee Robert 3 Pepper Distinguished Professor Chair of EECS UC Berkeley Invited Talk Workshop Foundations and Applications of Componentbased Design Seoul Korea Oct 26 2006 Key Concepts in ModelBased Design Specifications are executable models Models are composed to form designs Models evolve during design Deployed code is generated from models Modeling languages have formal semantics Modeling languages themselves are modeled 000000 For generalpurpose software this is about 0 Objectoriented design For embedded systems this is about 0 Time 0 Concurrency Lee Berkeley 2 What We Have Learned Embedded systems demand a different approach to computation Lee Berkeley 3 Instead of a Program Specifying f 01 gt 01 a partial function from bit sequences to bit sequences Lee Berkeley 4 A Program Should Specify f T gt O1P gt T gt O1P actor H J a signal signal where T is a partially ordered set representing time precedence ordering causality synchronization etc Lee Berkeley 5 This Leads to What We Call ActorOriented Component Composition X E T gt 01 Some of the Possible 1 I p5 Models of Computation TimeTriggered Discrete Events Data ow o Cascade connections 39 RendeZVOUS SynchronousReactive 0 Parallel connections Continuous Time 0 Feedback connections Mixtures of the above If actors are functions on signals then the nontrivial part of this is feedback Lee Berkeley 6 000000000000 Examples of ActorOriented Languages CORBA event service distributed pushpull LabVlEW dataflow National Instruments Modelica continuoustime Linkoping OPN ET discrete events Opnet Technologies Occam rendezvous ROOM and UML2 dataflow Rational IBM SCADE and synchronous languages synchronousreactive SDL process networks Simulink Continuoustime The MathWorks SPW synchronous dataflow Cadence CoWare VHDL Verilog discrete events Cadence Synopsys The semantics of these differ considerably but all can be modeled as f T gt 01P gt T gt 01P with appropriate choices of the set T Many of these are domain speci c Many of these have visual syntaxes Lee Berkeley 7 O The Catch f T gt O1P gt T gt O1P o This is not what mainstream programming languages do 0 This is not what mainstream software component technologies do Let s deal with this one first Lee Berkeley 8 How much Theory is Based on f O1 gt O1 o Effectively computable functions Turing Church 0 Operational semantics as sequences of transformations of state Various 0 Denotational semantics as functions mapping a syntax into a function that maps state into state Winskel o Equivalence as bisimulation Milner 0 Verification as model checking Various See Lee FORMATS 2006 for further discussion of this Lee Berkeley 9 Our Approach to a More Suitable Theory The Tagged Signal Model Lee amp SangiovanniVincentelli 1998 A set of values V and a set of tags T An eventiSe 6 Tx V A signals is a set of events la 5 c T x V A functional signal is a partial function 5 T gt V The set of all signals S 2 V 00000 Related models Interaction Categories Abramsky 1995 Interaction Semantics Talcott 1996 Abstract Behavioral Types Arbab 2005 Lee Berkeley 10 Actors Ports and Behaviors An actor has N pon s P 171 193 72 174 A behavior is a tuple of signals 6 SN An actor is a set of behaviorsA c SN Lee Berkeley 11 Actor Composition Composition is simple intersection Lee Berkeley 12 Connectors Connectors are typically trivial actors 4 CCS secgts2s3 AA1mA2mc Lee Berkeley 13 Functional Actors 0 Ports become inputs or outputs 0 Actors become functions from inputs to outputs 19139 p2 ACS4 V 39 39 v sseAs1 s1s2 s2 Lee Berkeley 14 For Functional Actors Arbitrary Composition has a FixedPoint Semantics Lee Berkeley 15 Structure of the Tag Set The algebraic properties of the tag set Tare determined by the concurrency model eg Process Networks SynchronousReactive TimeTriggered Discrete Events Data ow Associated with these may Rendezvous be a richer model of the connectors between actors Continuous Time Hybrid Systems Lee Berkeley 16 Example of a Partially Ordered Tag Set T for Kahn Process Networks Ordering constraints on tags imposed by communication SigmaQ Lactor O gtO O O quot0 0 S Each signal maps a I r IiiI totally ordered subset y n n e n of T into values Z a r r r Example from Xiaojun Liu PhD Thesis 2605 F39 I El l Example Tag Set Tfor Kahn Process Networks Ordering constraints on tags imposed by computation Z Actor Flin z u out v repeat u t1 receivez t2 receiveu sendv tl t2 V Actor F2in x out y x repeat t receivex y sendv t Composition of these constraints With the previous reveals deadlock Example from Xiaojun Liu PhD Thesis 2005 Lee Berkeley 18 Totally Ordered Tag Sets 0 Example T N synchronous languages 0 Example T R0 gtlt N with lexicographic order super dense time Used to model hardware continuous dynamics hybrid systems embedded software See Liu Matsikoudis Lee CONCUR 2006 Lee Berkeley 19 0 Recall The Catch f T gt O1P gt T gt O1P o This is not what mainstream programming languages do o This is not what most semantic theories do Let s look at the second problem next Lee Berkeley 20 ActorOriented Design Established component interactions class name data r methods call return The alternative Actor oriented actor name data state parameters pods Input data Output data Lee Berkeley 21 The Key To Success Separation of Concerns 0 Concrete Syntax o SyntaxBased Static Analysis eg Type Systems 0 Abstract Semantics 0 Concrete Semantics o SemanticsBased Static Analysis eg Verification Lee Berkeley 22 0 An Abstract Syntax connection Entity Relation Entity Port L k Port Attributes Attributes Entities Attributes on entities parameters Ports in entities Links between ports V dth on links channels Hierarchy Attributes Abstract syntaxes can be formalized See Jackson and Sztipanovits EMSOFT 2006 Lee Berkeley 23 O MetaModeling of an Abstract Syntax I0 Using GME from 232 Vanderbilt an abstract a inputs eld syntax is specified as an iti n zfeloniil ComponentEnmy object model in UML c l bde39 with constraints in 0 0 OCL or alternatively Pon Relation With MOF Atom 0 ltltAtomgtgt 0 Such a spec can be used to synthesize IndirectLink visual editors and cmnem models transformers InputPort OutputPort 0 ltltAtomgtgt ltltAtomgtgt Ra 0 1 Metamodel of Ptolemy II abstr act syntax DirectLink f CompositeEntity COHSTF UCTCd in Connectiongtgt Nbde39 n H Y Zheng 0 t I Lee Berkeley 24 The Key To Success Separation of Concerns 0 Abstract Syntax i 16l39iiliii ll jiiiiaixr o SyntaxBased Static Analysis eg Type Systems 0 Abstract Semantics 0 Concrete Semantics o SemanticsBased Static Analysis eg Verification Lee Berkeley 25 Concrete Syntax Example concrete syntax in XML ltentity namequotFFTquot classquotptolemydomainssdflibFFTquotgt ltproperty namequotorderquot classquotptolemydataexprParameterquot valuequotorderquotgt ltpropertygt ltport namequotinputquot classquotptolemydomainssdfkernelSDFIOPortquotgt ltportgt ltentitygt ltlink portquotFFTinputquot relationquotrelationquotgt ltlink portquotAbsoluteValue2outputquot relationquotrelationquotgt XML and XSLT have made concrete syntax even less important than it used to be Going a step further GReAT from Vanderbilt works with GME to synthesize model transformers from meta models Lee Berkeley 26 The Key To Success Separation of Concerns 0 Abstract Syntax 0 Concrete Syntax g r t i 39K 0 Abstract Semantics 0 Concrete Semantics o SemanticsBased Static Analysis eg Verification See Lee and Neuendorffer MEMOCODE 2004 and Xiong PhD Thesis 2002 for actororiented type systems Lee Berkeley 27 The Key To Success Separation of Concerns 0 Abstract Syntax 0 Concrete Syntax o SyntaxBased Static Analysis eg Type Systems r n l l ruib39w x H39mlii of v v w m all ll all y it ll ll liegli ll 0 Concrete Semantics o SemanticsBased Static Analysis eg Verification Lee Berkeley 28 o 0 Where We Are Headed An Abstract Semantics A Fi neir Abstract Semantic rz Lee Berkeley 29 Tagged Signal Abstract Semantics Tagged Signal Abstract Semantics an actor is a subset of the signals with which it interacts P C S1 x 52 Process 51651 1 P signal is a set of events port may be an input or an output or neither or both It is irrelevant This outlines a general abstract semantics that gets specialized When it becomes concrete you have a model of computation Lee Berkeley 30 A Finer Abstraction Semantics Functional Abstract Semantics An actor is now a function from input signals to output signals F 51 gt 52 FunctionalProcess SIES1 quot F quot S2652 port is now either an input or an output or both This outlines an abstract semantics for deterministic producerconsumer actors Lee Berkeley 31 0 Another Finer Abstract Semantics Process Networks Abstract Semantics sets of signals are monoids which allows us to incrementally construct them Eg stream event sequence rendezvous points An actor is a sequence of operations on its signals where the operations are the associative operation of a monoid P C S1 gtlt S2 ThreadProcess sles1 P gt S2652 Actor is not necessarily functional can port is either an be nondeterministic input or an output or both This outlines an abstract semantics for actors constructed as processes that incrementally read and write port data Lee Berkeley 32 Concrete Semantics that Conform with the Process Networks Abstract Semantics Communicating Sequential Processes CSP Hoare Calculus of Concurrent Systems CCS Milner Kahn Process Networks KPN Kahn Nondeterministic extensions of KPN Various Actors Hewitt 00000 Some Implementations o Occam Lucid and Ada languages 0 Ptolemy Classic and Ptolemy ll PN and CSP domains 0 System C o Metropolis Lee Berkeley 33 Process Network Abstract Semantics has a Natural Software Implementation execution control data transport send0 t receiverputt init fire P1 E1 token t IORelation IOPort Receiver inside port Lee Berkeley 34 Process Network Abstract Semantics in Ptolemy actor contains ports I f ltlt Interface Actor IOPort ptolemyacto r Director gefDrecfor0 39 Direcfo getchannelndex int Token hasRoomchannelndex int boolean hasTokenchannelndex int boolean isnput boolean isOutput boolean sendchannendex int token Token ltlt Interface creates director creates receivers Receiver gef 39 Token gefConfaner0 39 IOP f hasRoom 39 boolean has Token 39 boolean puff39 Token sefConfaner60 f IOPo I port contains receivers I I receiver implements communication I monoid operation to incrementally construct signals Lee Berkeley 35 Several Concrete Semantics Refine this Abstract Semantics Receiver 39 lOPorT Toke70 booean Mailbox QueueReceiver 11 11 11 FlFOQueue ArrayFlFOQueue 36 O A Still Finer Abstract Semantics Firing Abstract Semantics An actor is still a function from input signals to output signals but that function now is defined in terms of a firing function signals are in monoids can be incrementally constructed eg streams discreteevent signals F S1 gt S2 FiringActor 1651 gtF1fgt 2 652 port is still either an input or an output The process function F is the least fixed point of a functional defined in terms off Lee Berkeley 37 Models of Computation that Conform to the Firing Abstract Semantics o Dataflow models all variations 0 Discreteevent models 0 Timedriven models Giotto ln Ptolemy ll actors written to the ring abstract semantics can be used with directors that conform only to the process network abstract semantics Such actors are said to be behavioraly polymorphic Lee Berkeley 38 Actor Language for the Firing Abstract Semantics Cal Cal is an actor language designed to provide statically inferable actor properties wrt the firing abstract semantics Eg actor Select S A B gt Output action 5 sel A v gt v guard sel end action 5 sel B v gt v guard not sel end end lnferable firing rules and firing functions U1 2 lttruevJgt v e Zf1 true v JgtH v U2 ltfalseJ v v e z f2 ltfalseJ vgtH v Thanks to Jorn Janneck Xilinx Lee Berkeley 39 A Still Finer Abstract Semantics Stateful Firing Abstract Semantics An actor is still a function from input signals to output signals but that function now is defined in terms of two functions Fle gtS2 signals are monoids can be incrementally constructed eg streams discreteevent signals Stateml ctor f 51 X Z gt 52 State Space port is still either an input or an output g S1 x Z gt Z The function f gives outputs in terms of inputs and the current state The function g updates the state Lee Berkeley 40 Models of Computation that Conform to the Stateful Firing Abstract Semantics o Synchronous reactive 0 Continuous time 0 Hybrid systems Stateful firing supports iteration to a fixed point which is required for hybrid systems modeling In Ptolemy ll actors written to the stateful firing abstract semantics can be used with directors that conform only to the firing abstract semantics or to the process network abstract semantics Such actors are said to be behavioraly polymorphic Lee Berkeley 41 0 Where We Are Tagged Signal Semantics Process Networks Semantics Firing Semantics Stateful Firing Semantics Lee Berkeley 42 O 0 Where We Are Tagged Signal Semantics Process Networks Semantics F b39 m 7 39 Giotto Lee Berkeley 43 Meta Frameworks Ptolemy ll Tagged Signal Semantics Process Networks Semantics N Ptolemy emphasizes construction of behaviorally polymorphic actors with stateful firing semantics the Ptolemy actor semantics but also provides support for broader abstract semantic models via its abstract syntax and type system Lee Berkeley 44 Models of computation can be systematically composed A Consequence Heterogeneous Composition Semantics SR Director Director requiring stateful ring semantics and exporting stateful ring semantics Siatefui Firing Composite Actor in2 Continuous Director Director requiring stateful ring semantics and exporting stateful ring semantics Functional Atomic Actor Stateful Firing Atomic Actor Direct requiring ring semantics Giotto Director 9 ring semantics in SDF Director Director requiring ring semantics and exporting ring semantics Firing Atomic Actor Statefm Firing Atom ic Pastor out Lee Berkeley 45 The Key To Success Separation of Concerns 0 Abstract Syntax 0 Concrete Syntax o SyntaxBased Static Analysis eg Type Systems 0 Abstract Semantics 0 Concrete Semantics Lee Berkeley 46 0 Interface Algebra for Causality Analysis An algebra of FEEL 4 interfaces provides operators 7 6 for cascade and parallel 0 composition and necessary and sufficient conditions for causality loops zerodelay loops and deadlock b C See Zhou and Lee EMSOFT 2006 Lee Berkeley 47 0 Recall The Catch f T gt O1P gt T gt O1P o This is not what mainstream software component technologies do 0 This is not what most semantic theories do Let s look at the rst problem last Lee Berkeley 48 Programming Languages 00 O Imperative reasoning is simple and useful Keep it The problem is that timing is unpredictable Fix this at the architecture level Replace cache memories with scratchpads Replace dynamic dispatch with pipeline interleaving Define decidable subsets of standard language Deliver rigorous precise and tight WCET bounds Lee Berkeley 49 Conclusion The time is right to create the 21 st century theory of embedded computing MELIU Lee Berkeley 50 f Telcordla Technologies A WWW m cm W H An Approach to Execu ng Ptolemy Class c Models under Ptolemy ll Dru m Richanh Neil Smym curren ywnh Ame Mm Goodman chus Pang 698 Ml Pm emy Mmmumevence ka suppuned m pan bythe Mavch 23m 2mm MST Advance Technumgy Pvugvam mm Campll w Motlva Ion Swmu atmn Framevvu kfur Phutumcs CAD Cunsumum F39CA U Ptmemy C assu Wave ength Dumam Swmu atur WDS frum MONET Why nut siay mm Ptmemy ma uHhe J 55m avarbased V2ng w and mated mpmvemems 7 m ChemServer arcmemure acruss Wmdu s and UW p atfurms 39vmmu mam cm frewcordua 39 Technologes PCAD Team Telcordlam Technologies wquot m F B If A17 Employee wned company Expc encc V RSoft Inc Research Software Agilenit Founding associate A NETWORKS Ptolemy Miniconference Mar 23 2001 3 TEICDTCIIa Technologies I u quotmmv m w 39 1nAr Internal Structure of Benes Switch SwitchZS DelayCorver Null lato H Swltch MZlnter feromet 070 R I Er y I ServoAtterIuatol E Splutt E s Q I 39 BlackHole Swltchz O O wdsDeiay Abs Telcmdla Technologes Ptolem 39 39 Mar 001 4 Sample Output wavelmgms m ba lo r iteration a mam I cvusstawk r Lhannel a mu have pompafmmance 7 wan w aw wa2 w as w 54 w aa was w 57 w as was w an Exwt Prwnt HTML About Telcordla non se Technologies w wwv wwwwwwwww HowawwyMwnmrwlaenueMarZJ 2mm mework Approach Vergil GUI m m Ptolern II Ptolemy Classic Ptcl Server Telcofdla 39 TechnologIes Components of the Hybrid System Augmented pt ang nude 92 r 7 Parameters names types and dEVaquames 7 Fun names dwemmnamy and datatypes 7 Emds ave rccm descnptmn m acmr Wrm eeraun rccms Ptchrrecmrcrass 7 Dues nm schedme m we anyJava ems dwec y 7 Creates a scum descnbmg mpmcgy and parameters uHhe Unwevse 7 Opens a cumrm sucke mm V2ng c a pm server msmce 7 Creates a smg e P mR esuH mstance and advemses Ms sucket pun PrutResurt crass 7 Opens a smg e server sucket er P utR esuH requests 7 Manages c Frame mstancesmv msp ay er srmuxancn vesuhs 7 Drsu bums mcummg srmuxancn vesuh data m the curved mmFrame Components of the Hybrid System cont Pto emyTCL pm rmerpreter 7 nterpreter unchanged rrcm the standard F39tu emy C assu versmn 7 Drspxay mass m kerne rs rep aced by the Walter chPmuer masses 7 Funcucms er pxgraph rep aced by P utREsu t chant nude VergH Conrrguratron vergHCon gurann xrm cm cmues a arrecmr derwed rrcm Prcxorrecmr 7Acmr Lrbrary mdudes a p acehmder acmrrcr Each C assu siar Server Drspatcher 7 rspatches a separate pm server mstance fur Each swmu atmn run 7 Mu up e mude Wmduvvs can be ripened and run srmuuanecusxy 7 C mstance can crash wrmcm affectmg cmer current srmuxaucns frewcurdua 39 Technologes Process Flows Mode Creamery 7Tne user creates a mude frumthe p acehmder acturs 7Tne user cun gures actur parameters and dream parameters 7Tne mude 5 saved as a MDML unwerse ur ga axy Mode Execuhon m Pthwrector 7 Pre re 7Tne mude scum s eveamd m the pm anguage 7Asueke s upene m a new pm mstance 7Tne scum shansmmed and mtevpveted enms ave eaugm 7 Fne 7A scum s senneumg meme execme the mude N devauuns vun N 7 Pust re 7 Swmp y vetumsmse 75m Fne 7A nan scum s sennu Mat and haHR equested s 52 Ta rdl quot rec ndiges Process Flows continued P omng 7 Stars redumng Siam p uts ur hws mgrams mstarmate a Wetter 7 Stars redumng mumneratmn sequence p uts mstarmate a TF uttEr 7AddPennt 5 used m end data pmnts m edner ss 7 P utter terrmnate furmats and sends a p uvmstugram as P utML 7Tpxuner mmahze eauses an Empty P utFramE m be sued and drawn 7pruner Ermmate eauses une pumttu be added m eaen dataset rrors 7 Errurs caught durmg smptmg are repuned un Var n 7 Errurs caught by me mterpreter are returned an the centred sucket Tekordla Technologes Caveats Not tntended to sotxe tne generat probtern r Onty tested thh SDF dumam 7 Some features ummp emented e rnuttrportnotes No toxens pass orrectty between Java actors and c stars Type rntsrnatcnes between Ptoterny H and ctasstc Strnutatton Controt and ErrorRepomng are not cornptete aretcordta Technologtes Summary Ptoterny ctasstc strnutattons can be bth and executed H v Vergtt ctasstc ttnxage ptugs searntessty tnto Ptoternyt Maxeme support forVWvdoWs DLL S and UNtXLtnux snared hbS Tne ptct servers can execute on one orrnore rernote nosts Performance easemtaHythe sarne as Ptoternyctasstc executton Java actors are generated automattcaHy by pttang extenstons Most buHHn SDF stars functton H v tne Hybrtd SySIem except 7 Same specta purl data types are nut Suppuned 7 Stars usth pxgrapn Wm drsptay un tne server machtne fretcordta 39 Technologes Network Design Tools Inc Spun off from Telcordia Technologies March 2001 Located in Monmouth County New Jersey Based on three software tools from Telcordia Applied Research Waveength Network Designer WaND Strategic Analysis Tool SWAT Waveength Domain Simulator WDS Telcordia Technologies My l m i Ptulemy MlnlEDMEYEHEE Mar 21200113 Benes Switch with Sources and Sinks Edireuorlibraw Ecrapms kHaleD alukHuieu ans wizcnA sf 4 RegenH12 b Telcordla Technologies Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in M08102 UC Berkeley Spring 2008 ONLY Bryan Krantz University of California Berkeley MCB 102 Spring 2008 Metabolism Lecture 3 Reading Ch 14 of Principles of Biochemistry Glycolysis Gluconeogenesis and the Pentose Phosphate Pathway Preparatory Phase of Glycolysis continued STEP 4 Splitting Fructose 16bisphosphate Fructose 16bisphosphate 69 Dihydroxyacetone phosphate Glyceraldehyde 3phosphate Aldolase We used 2 ATP to generate fructose e 2 1 2 CH20P03 CH20P03 16 bisphosphate The sixcarbon sugar molecule 0 is split in the middle producing two threecarbon 5 H H0 2 molecules Note CC bond cleavage is rare in H 4 3 0 aldo39ase biochemistry OH H Fructose 16bisphosphate o H Mechanism Aldolase name is derived from 1CH20P0 39 MCI aldol condensation reaction in organic mco 5040 chemistry and involves the formation of a 30420 60420 covalently linked substrateenzyme intermediate Dihydr0xyacetone Glyceraldehyde I I I I phosphate 3phosphate The epsilon amino group of lysine in the enzyme Age 238 mm active srte makes a nucleophilic attack on the carbonyl carbon forms a protonated imine at C2 or a protonated Schiff base water is eliminated glyceraIdehyde3phosphate leaves and water comes into to release the enzymelinked DHAP by a reversal of the original Schiff base formation step Draw out mechanism in dataL Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in M08102 UC Berkeley Spring 2008 ONLY How do we know this mechanism Proof of the 2013 H CHZOPi H mechanism comes from use of a reducmg agent 0 null H20 CL i Eggmozguigm I I Z 3 sodium borohydride to produce a reduced amp stable HO H H mead H 31331 13 39 r tio39 secondaryamineenzyme adduct Thus the Hf OHq Efnaui n m H C OH fructose16 bisphosphate stably links to the H2om gHzopi enzyme 01 H ij OH fl120E III CH2OPi 0 H II HO C H M Resonance stah jzationof thecarbanion How is catalysis of the 00 bond possible The H H233 CHZOP H j mamma l l l quaternary nitrogen has tremendous electron Hf jg if CH OP H raga g l pulling power A negatively charged carbanion 220 intermediate stabilizes the strong electron pulling CHZOH power of the nitrogen to generate the strong electronpulling center Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in M08102 UC Berkeley Spring 2008 ONLY STEP 5 Triose Phosphate Isomerase Dihydroxyacetone phosphate DHAP 69 Glyceraldehyde 3phosphate Mechanism Parallels phosphoglucoisomerase ie converting an aldehyde sugar into a ketose CH CH ocII a typical general acidbase catalyzed reaction An I 2 enediol intermediate forms C0 triose phosphate HCOH isomerase CHZOPO CHZOPO D39h dro acetone Energetics The reaction of course as suggested I y xy Glyceraldehyde Phosphate 3phosphate by the small posrtive AG of 75 lemol is reversible and near equilibrium AG o 75 kJmol Symmetry Basically the 3carbon halves of the original 6carbon glucose have now been isomerized into identical 3carbon units End of the Preparatory Phase Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in MCBlO2 UC Berkeley Spring 2008 ONLY voff Phase STEPS 610 STEP 6 Glyceraldehyde Phosphate Dehydrogenase Example of a reaction coupled to oxidationreduction Glyceraldehyde 3phosphate GAP Pi NAD6913Bisphosphoglycerate BPG NADH H Energetics Adding inorganic phosphate onto an organic compound is generally an uphill reaction But the reaction is not Why Acetaldehyde Acetic Acid E 057 V NAD 9 NADH E 032 V A downhill reaction is coupled to the uphill reaction of adding Pi onto GAP forming acyl phosphate ie AE gt 0 A very high energy bond is made Mechanism Glyceraldehyde phosphate dehydrogenase has one crucial cysteine residue You can chemically modify the SH 0 H C NAD NADH H HCOH HO lr O39 glyceraldehyde CHZOPog o 3phosphate Glyceraldehyde Inorganic dehydrogenase 3phosphate phosphate 0 ll 0 O P O l i 039 HCIZOH CHZOPO AG 63 kJmol 13Bisphosphoglycerate group of the cysteine When you chemically modify the residue the enzyme activity is eliminated The SH side chain is essential for activity The cysteine sulfhydryl makes a nucleophilic attack on the electronpoor carbonyl carbon of the aldehyde Upon release of the proton a thiohemiacetal is formed between the compound the SH Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in M08102 UC Berkeley Spring 2008 ONLY A hydride moiety the proton plus two electrons is transferred onto NAD This is a strongly downhill reaction The oxidation is on the carbon This is aided by the abstraction of the proton on the OH group ending up with a thioester Thioesters The hydrolysis of thioesters is much more strongly downhill than the hydrolysis of simple esters Oxygenbased esters like this give resonance stabilization so that both of the oxygen atoms carry a somewhat similar partial negative charge With thioesters because of the size difference between oxygen and sulfur there is not much of this resonance stabilization When hydrolyzed thioesters therefore generate higher amounts of free energy Phosphorolysis In this final reaction to release product instead of water Pi splits the thiolester bond This carbon in the thioester bond is the most electronpoor atom here As a result the mixed acid anhydride product is released and the phosphate bond is super highenergy Arsenate When you do glycolysis and you break open yeast cells glycolysis does not happen in the absence of phosphate What would happen if you were to add arsenate instead of phosphate Arsenic is right under phosphorus in the Periodic Table Arsenate looks almost exactly like inorganic phosphate Arsenate will react in the glyceraldehydes phosphate dehydrogenase reaction You get an analog of 13bisphosphoglycerate except that the phosphate on the onecarbon is replaced by arsenate This gets the system into trouble Unlike 13bisphosphoglycerate this compound with the arsenate analog is unstable lt spontaneously gets hydrolyzed and you lose this analog of the energy rich phosphate You cannot generate ATP lfyou are doing this with phosphate then you have a super highenergy phosphate bond here so you can take advantage of it Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in MCB102 UC Berkeley Spring 2008 ONLY STEP 7 Phosphoglycerate Kinase A payoff step Mechanism The reaction uses the high energy phosphate bond and ADP as an acceptor ofthis phosphate on C1 of BPG to generate 3phosphoglycerate amp ATP Eneretics The backward reaction does not occur easily because this phosphoglycerate kinase reaction has a reasonably negative standard free energy change of 185 kJmol Thermodynamically the reaction is spontaneous The initial phosphate bond at the one position is highenergy phosphate bond How much was the BPG phosphoanhydride bond worth ADP Pi 9 ATP BPG e 3PG AG 305 lemol BPG ADP BPG ATP AG u 185 lemol cquot o O P O39 9 c o HCOH CH20P0 39 13Bisphosphoglycerate my ADP phosphoglycerate 2 Mg kinase I O PO o o f 9 HCOH 9 CHZOPO 0 Eli 3Phosphoglycerate ATP AG o 185 kJmol Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in M08102 UC Berkeley Spring 2008 ONLY STEP 8 Phosphoqlvcerate Mutase 3Phosphoglycerate 3PG 69 2Phosphoglycerate 2PG A mutase is a class of enzymes O 039 0 039 thatmove a R group from one M 2 posmon In the molecule to another C 9 position in that molecule Here the R HC0H phosphoglycerate H o Po3 group iS Pi I mutase CHz O P0339 CHz OH Mechanism The oddity is that the reaCtiO Starts With phosphorylated 3Phosphoglycerate 2Phosphoglycerate Phosphoglycerate Mutase enzyme E Pi EPi donates its Pi onto the CZ of A6 44 kJmol the substrate 3PG creating the intermediate 23bisphosphoglycerate 23bisPG Next the 23BPG will donate its 3Pi onto the enzyme to generate 2 phosphoglycerate 2 PG and then regenerate EPi EPi 3PG 69 E 23bisPG 69 EPi 2PG Eneretics AG is near zero and near equilibrium since the substrate was remodeled subtly such that a simlar phosphanhydride bond was broken and then remade Phosphoglucomutase An analogous enzyme which regulates entry into glycolytic pathway in muscle phosphoglucomutase uses a similar mechanism More soon Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in MCB102 UC Berkeley Spring 2008 ONLY STEP 9 Enolase By removing water this step increases the hydrolysis potential of the phosphate 2Phosphoglycerate 2PG 69 Phosphoenolpyruvate PEP H20 O 39 O O Eneretics Hydrolysis of the phosphate on C0 H20 C 2phosphoglycerate cannot generate much I energy But enolase does an internal HCOPO3 enolase opo3 rearrangement a dehydration reaction to HO CH2 CH2 make PEP Now the same phosphate bond 2Phosphoglycerate Phosphoenolpyruvate behaves as a super highenergy bond AG 0 75 kJmol Mechanism You abstract the proton from CZ of 2 PG that is followed by an elimination of the hydroxyl group Abstraction of the CZ proton is not easy because it is not very acidic Enolase uses a magnesium ion Mg2 The reactive center of the enzyme contains a couple of Mg2 s to help abstract the proton generating PEP Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in MCB102 UC Berkeley Spring 2008 ONLY STEP 10 Pyruvate Kinase Again the name of the enzyme does not tell you the direction in which the reaction proceeds PEP ADP Pyruvate ATP Eneretics Although two molecules of ATP were spent a total of four molecules of ATP were recovered Mechanism Type of substrate phosporylation mechanism Physiological Mg2 in the active site is required M n2 also works Fluoride inhibition Fluoride is a classic inhibitor of glycolysis discovered by Otto Warburg in 1941 It modifies the phosphate and magnesium in enolase leading to controversy regarding the fluorination of drinking water o 039 Y i 9 o P O 9 CH2 039 O ADP Mg K pyruvate kinase Phosphoenolpyruvate I f 39O PO ZO 9 CH3 Pyruvate 9 O m Adenine AG 314 kJmol ATP 0 0 O 039 C C C OH CO II tautomerization I CH2 CH3 Pyruvate Pyruvate enol form keto form Metabolism Lecture 3 GLYCOLYSIS PT 2 Restricted for students enrolled in M08102 UC Berkeley Spring 2008 ONLY Glycolysis in anaerobic conditions Pyruvate NADH 9 Lactate NAD The enzyme is called lactate dehydrogenase This gets rid of the NADH that was generated during the glyceraldehyde phosphate dehydrogenase step and regenerates NAD At this point there would be no net oxidation or net reduction during glycolysis Muscle cells do this to maintain levels of NAD in the absence of Oz 1 Course Introduction The Information amp Service Economy 27 August 2007 Bob Glushko amp AnnaLee Saxenian 10f26 Plan for Today39s Lecture Introductions What is a Service Syllabus Overview Assignments and Administrivia 20f26 3of26 So What is a Service The Economist quotServices are anything sold in trade that cannot be dropped on your footquot Most people understand or think they do what makes something a product or goods Goods are things that can be owned traded and distributed to different places at different times without changing their identity But there is much less agreement about the definition of service Intangible Perishable Experiential Coproduced between the service provider and service consumer News quotService sectorquot growth slows WMoneycom OME NEWS MARKETS TECHNOLOGY JOBS 5 ECONOMY PERSONAL FINANCE Service sector growth slips December s ISM index edges lower but decline in line with Wall Street39s estimates pricespaid component rises new orders fall January 4 2007 1233 PM EST NEW YORK Reuters a Growth in the service sector slowed in December following a lessthanexpected rise in factory orders the previous month reports showed Thursday pointing to a slackening economy 4 of 26 5 of 26 Services as a Category for Economic Analysis Q Q Q 43 Q lt0 9 32 b b 9 0939 3 9 Q99 Services Manufacturing Agriculture But A quotResidualquot Definition Isn39t Very Useful Service sector is gt70 of GDP in US and other developed countries gt 52 in developing countries Fastest employment growth is in service sectors 1 Professional amp business services 2 Health amp education services 3 Leisure amp hospitality services 60f26 News Hotel Industry Consultants Had a Good Year HVS International reports strong demand for its services in 2006 Jan 10 2007 HaltIN Week In Review leek in Review Steve Rushmore President and Founder of IIVS International the leading global hospitality services and consulting rm proudly announces that 2006 proved to be another successful year Worldwide the rm was involved in nearly 3000 hotel assignments quotIn the New York of ce alone Rushmore explains we were engaged in more than 700 consulting and service assignments exceeding 2005 s total of just 7 of 26 News SelfService Banking with ATMs Hits China wmm Fliiifjif Fm W 4m 5quotquot A5 ufThursday Dacemhams znus Mama Technoluml Pelsnnal Inumal ATM Dynasty Dawns for Chinese Banks Cash Machines Are Replacing People as Cost Cutting Fares Bloated Paymlls Week1mm Leisme 3 JAMES 1 mm mnn39ws uswsrnpm Decenw er 339 2005 Page 53 ULmm A am SHANGHAI China Chinese banks are quickly shedding mmnmm mom employees from their bloated ranks but they are eager to deploy one type of worker the ATM 8 of 26 9of26 SelfService In quotSelfservicequot a service provider takes an activity formerly performed by an employee and allowsrequires the customer to do it generally to reduce costs The customer might do the same work done previously by the employee using the same facilities or equipment eg laundromat cafeteria But more often the employee has been replaced with an automated system involving software andor equipment eg ATMs kiosks touch tones gt IVR web sites for commerce tracking etc Selfservice allows for 7day 24hour services and this flexibility and convenience is valuable to customers 10 of26 News Cisco Systems quotServicifiesquot its Products WEE Cisco Not a Network Box Seller Anymore 3v Paula Musich ecember 13 2006 Cisco Systems may end up being thought of as a software company ve years from now rather than a networking box suppHer if ts 1etworkis the platform strategy is successful The Trend Toward Services for Hardware Firms 100000 333000 950000 WWW 520000 SGI39ViCE Revenues SM 1999 2000 I411 NE 21193 2W I6 of Revenue from Swim 39SeMce Memes HDW Revenue from Sandces Service Reva nue Growth Prod Lllct Re I e nue Growih 548 110f26 ThequotProduct Life Cyclequot Is also a quotServices Life Cyclequot Determining requirements and justifying purchase ofthe product Finding a product supplier Financing the product Installing the product Modifying other products or processes to work with the product Maintaining the product and replacing parts Training personnel to use the product Upgrading the product Disposing of product waste Disposing ofthe product 12 of26 Tangible v Intangible Goods v Services Intangible goods have all of the economic characteristics of tangible goods but no physical dimensions or spatial coordinates Intangibles have always existed but have become far more economically significant because of dramatic innovations in information technology Classic examples of intangible goods are music legal documents software 13 of26 Software as a Service Significant amount of enterprise or quotpackagedquot software is being transformed from an installed product to a hosted service CRM HR Bl are significant sectors Supply Chain and ERP are coming Instead of installing the software on a local machine the customer pays on a subscription or per use basis to access the functionality using a Web browser Many quotdeployedquot software applications have become hybrids with a significant hosted or quotvendormanagedquot S asaS component 14 of26 15 of26 News Microsoft Offers quotSoftware As A Servicequot Microsoft To Offer Software As A Service CRM This Summer Hosted CRM already is available through Microsoft business partners but the company plans to irectly sell an offering it39s calling Microsoft Dynamics CRM Live By Mag Hales Weier InformationWeek Jan10 2007 0900 AW Microsoft will offer its customerirelatlonship management product via a so ware as a sewioe Salas model but Interested customers wlll have to wait until summer The company will announce today it39s sxarting to preview its nextgeneration CRM product to business partners and expects to have it available for purchase in the third quarter 16 of26 News Web APIs Enable the quotProgrammable Webquot and Service quotMashupsquot Programmablemeb E Keeping you up to date with the latest onE Total mashups and the new Web 20 APIs Mashups January 13 2007 1447 Mashup of the Newest Mashups Day gtgt TataiAlpfE The Found Bin The Found Bin 356 NOTAM Ace MashupsDay Food Tube 298WFM39A Adding Tags to MyBlogLog tittt First time We Maps ere See Dashboard I Vastcom Clirk for an annlllar Mh iv Mahg ump nut 17 of 26 Web Services Web Services with a capital quotSquot generally means a particular set of speci cations developed by OASIS WSl or similar standards organization for sending XML documents as the request and as the response from some service function process whatever But a quotwebbased servicequot with a lowercase quotsquot can be de ned as any networkbased functionality that is invoked and delivered by XML documents Almost any service can be implemented to use documents as interfaces request and response A quotmashupquot of information from different services is accomplished through services requested via web APls Web Services andvs Service Oriented Architecture Web services are an important physical architectural idea and a set of standards and techniques Service Oriented Architecture SOA is a conceptual architectural perspective and design philosophy to think about quotwhat a business doesquot in more granular terms so that a business can be a mix of core internal functions that it does itself and outsourced ones provided by other businesses MBAs and ClOs talk about SOAs software architects and developers talk about web services 18 of26 News Amazoncom quotProductizesquot its Web Services Evolving Amazon39s services into products Developing inlernai Web services is easy the hard para is bringing them to market By Jon udeli a October 04 2006 The annowncements from Amazon Web Services LLC just keep on coming The iaiest news ash is FBA Fui iimeni by Amazon which will make Amazon s warehouse iis customer serVIce and its pick pack and ship machinery avaiiabie to sellers 19 of26 20 of 26 News IBM Standardizes Consulting as quotService Productsquot IT services Application services Business consulting Business processes Business IE 3 ob ilquotquotu39iCE 3 New IBM service products ease information management and storage of data Summary IBM unveilis first service products for endtoe nd infarmation management Pubiished 190ct2 005 Industry Crossrindustry Defining quotServicequot Like the Blind Men quotDefiningquot the Elephant 21 of 26 A Tour of the Syllabus Saxenian Course Deliverables Assignment 1 101108 Analyzing a Service System Assignment 2 10221029 Take Home Short Answer Midterm Term Paper proposal clue 115 final paper due 1214 23 of 26 Grading Assignments 1 and 2 20 each of course grade Class participation 10 Term paper 50 24 of 26 Course Administrivia Sign up for quoti210quot mail list by sending mail to quotmajordomoischoolberkeleyeduquot with body quotsubscribe i210quot Course reader available tomorrow at Copy Central 25 of 26 Introductions Who are you and why are you here 26 of 26