Extrinsic-intrinsec concept and complementarity

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(Extended Abstract)

Computing safe winning regions ofparity games in polynomial time(Extended Abstract)Adam Antonik,Nathaniel Charlton,and Michael HuthDepartment of Computing,South Kensington campus Imperial College London,London,SW72AZ,United Kingdom {aa1001,nac103,M.Huth}@AbstractWe propose a pattern for designing algorithms that are in P by con-struction and under-approximate the winning regions of both players inparity games.This approximation is achieved by the interaction ofﬁnitelymany aspects,each performing an eﬃcient static analysis.We present sev-eral such aspects and illustrate their relative precision and interaction.Keywords:model checking,partial information,abstraction,parity games1Introduction.Parity games G(e.g.[1])haveﬁnite or inﬁnite plays on labelled,directed graphs(V,E)and are played between two players(0and1) where the winning condition for inﬁnite plays is based on parities derived from a priority functionχ:V→{0,1,...,d−1}.Game G is then said to have index d.Parity games are determined(e.g.[9,4]):each player has a winning region of game positions for which she has a memoryless winning strategy,and these two regions form a partition of the set of game positions.For an example,consider the parity game in Fig.1.A possible inﬁnite play is v7v0v7v0···=(v7v0)ωwhich is won by player1as the largest priorityχ(v)that occurs inﬁnitely often in that play is1and therefore odd(technically,a maximum parity acceptance condition).In this game,the winning region for player0is{v4,v5,v6},and the winning region for player1is{v0,v1,v2,v3,v7};both sets partition positions.Designing algorithms for the computation of winning regions in parity games is an important theoretical problem as the corresponding decision problem“is a position won by player0?”is in UP and coUP[6]but not known to be in P. Designing such algorithms is also important for applications since determining winning regions in parity games is equivalent,in linear time and logarithmic space,to other important problems—we mention model checking formulas of the modal mu-calculus[3,1].Traditional approaches design algorithms that compute the exact winning regions of parity games,see e.g.the survey in[2].These algorithms are then either revealed not to be in P—by constructing defeating input games—or it is presently not known whether they are in P.In this paper we take a complementary approach.Instead of designing an algorithm that computes exact winning regions but has complexity that is unknown or known not to be in P,we present a design pattern for algorithms that are in P by construction but compute only subsets of winning regions by partitioning the set of positions11Figure1:A parity game,taken from[4].In circled(squared)positions player0(resp.1)may move.Edges indicate possible game moves,and priorities of positions are provided to the left of positions,e.g.χ(v6)=1.into three regions:wins of player0(W0⊆V),wins of player1(W1⊆V),and positions whose winning status is left open(V\(W0∪W1)).Our approach has practical relevance for at least two reasons.Firstly,in local model checking[8]one is only interested in whether a particular state satisﬁes a formula.This corresponds to determining which player wins a particular position,something our algorithms may well achieve.Secondly,our algorithms can be used as eﬃcient preprocessors:due to the invariants satisﬁed by both computed regions(detailed in Sec.2),one can abstract the original game so that each of these two regions collapses to a single winning position.Already existing algorithms,which are either known not to be in P or whose complexity is unknown,may then be used on those abstracted games to determine the winning status of remaining positions.In this extended abstract we refer to [1,9]for basic concepts of parity games.2Design pattern.In its essence,the design pattern we propose isW_0=Attr_0(G,{});W_1=Attr_1(G,{});cache=0;while(rank(G)!=cache){cache=rank(G);for(i=1;i++;i<=k){A#i;}}return(W0,W1);Throughoutσdenotes0or1,¯σmeans1−σ,and Attrσ(G,X)is theσ-attractor of set X⊆V is G.The basic invariant for this pattern is,technically speaking, that each Wσis aσ-paradise(as deﬁned in[4])and so a¯σ-trap,and aσ-attractor in parity game G.Also,any increase in the size of Wσdecreases the rank of G.Theﬁnal value of Wσrepresents those positions that are known to be won by playerσ,whereas V\(W0∪W1)contains those positions the algorithm does not classify.See Fig.2for illustration.This pattern is inspired by Zielonka’s constructive proof of determinacy for parity games[9],except that our pattern is symmetric and non-recursive.Aspects A#i perform eﬃcient static analyses that may decrease the rank of G,e.g.by increasing the size of Wσ.2maximal priority amongst undecided positions:n =χ(v )σ=n mod 2set of positions decided to be won by player 0W 0=Attr 0(G,W 0)Gset of undecided positionsV \(W 0∪W 1)W 1=Attr 1(G,W 1)set of positions decided to be won by player 1Design pattern invariant:W σis σ-attractor,σ-paradise,and ¯σ-trap in G .Figure 2:Computing safe winning regions of parity games:the set V of game positions is partitioned into regions W 0,W 1,and the complement of their union.Sets W σsatisfy a basic invariant,ensuring that all positions in W σare winning for player σ.3Aspects.Aspect A 1checks,for each position v ∈V \(W 0∪W 1)with 2≤χ(v )whether no cycle in (V,E )through v contains some position w with χ(w )=χ(v )−1.If there is indeed no such cycle,one can decrement χ(v )to χ(v )−2without changing the winning regions of G .Repeated application of this aspect gets rid of “gaps”in {χ(v )|v ∈V \(W 0∪W 1)},e.g.the missing 2in {0,1,3},whose absence may occur on-the-ﬂy,would change {0,1,3}to {0,1}.Aspect A 2,a dominance version of A 1,asks whether for any v ∈V \(W 0∪W 1)all cycles through v have some w =v with χ(v )≤χ(w ).If so,A 2re-sets χ(v )to 0without changing the winning regions of G .Unlike its strict version,based on χ(v )<χ(w ),A 2can resolve non-deterministic choices of such v .Aspect A 3abstracts intervals of odd (resp.even)priorities into an odd (resp.even)priority and solves,in P,a game for each such abstraction:n :=max {\chi(v)|v in V -(W_0+W_1)};//n as is Fig.2s :=n mod 2;//the \sigma in Fig.2Z_s ={};Z_{1-s}={};for (k =0;k++;2*k <=n){Z_s =checkInfFin({n,n-2,...,n-2*k},{n-1,n-3,...,n-2*k+1},s);if (Z_s !={}){W_s :=Attr_s(G,W_s +Z_s);}Z_{1-s}=checkInfFin({n-1,n-3,...,n-2*k-1},{n,n-2,...,n-2*k},1-s);if (Z_{1-s}!={}){W_{1-s}:=Attr_{1-s}(G,W_{1-s}+Z_{1-s});}}where +denotes set union,{n,..,n-1}is interpreted as {},and the method3checkInfFin(I,F,p)returns those positions in V\(W0∪W1)for which player p∈{0,1}can win all plays in the sub-game G[V\W p]such that“priorities set I is met inﬁnitely often,and priorities set F is met onlyﬁnitely often”.Finally aspect A4checks whether all cycles C through v have some w C with χ(v)<χ(w C);if so,A4increasesχ(v)to min Cχ(w C).4Interaction.By abuse of notation,we write A i1A i2...A ikfor the algorithmthat instantiates our design pattern with each A#i being A ik .In particular,A#imay equal A#j if i=j.We write{A i1A i2...A ik}if we mean any of the k!algorithms obtained by permutations of these aspects A ij .Fundamental questions are whether the interaction of these aspects com-mutes,whether swapping two aspects is in some sense conﬂuent,and whethercertain aspects can’t aid the progress of certain others.These questions are similar to the“phase ordering problem”in the design of optimizing compilers.For each instantiation,a suitable rank function has to be determined.A rankfunction for A3is rank(G)=|V\(W0∪W1)|.A rank function for{A1A3}, {A2A3},and{A1A2A3}is rank(G)=|V\(W0∪W1)|+ v∈V\(W0∪W1)χ(v). It is less clear whether a good rank function exists for{A1A2A3A4}as A4increases the value of the previously mentioned rank function.Example1.Algorithm A3completely solves the parity game in Fig.1but alsoH4,3as deﬁned in[7],an exponential worst-case input for the algorithm in[7].The interaction of aspects can improve the precision of algorithms derivedfrom our design pattern.We illustrate this point by means of a simple example. Example2.Let V={v i|0≤i≤3}withχ(v i)=i for all i,where player0 (resp.1)may move at v0and v1(resp.v2and v3).For E={(v0,v1),(v0,v3), (v1,v0),(v1,v3),(v2,v0),(v3,v2)}player1has no choice,A3computes empty sets Wσ,whereas{A2A3}completely solves this parity game:A2re-setsχ(v2) from2to0and then checkInfFin({3,1},{2},1)determines within A3that player1wins all positions.The full paper will feature additional aspects not presented in this extendedabstract,give a systematic account of the interaction potential of all of these aspects,and make some recommendations for instantiations of our design pat-tern.These recommendations will be backed up by experimental results that allow us to compare this approach to that of reducing parity games to SAT[5]. References[1] E.Gr¨a del,W.Thomas,and T.Wilke(Eds.).Automata,Logics,and Inﬁnite Games—AGuide to Current Research,LNCS2500,385pages.Springer Verlag,October2002.[2]H.Klauck.Algorithms for Parity Games.In[1].[3] D.Kozen.Results on the propositionalµ-calculus.TCS27:333–354,1983.[4]R.K¨u sters.Memoryless Determinacy of Parity Games.In[1].[5]nge.Solving Parity Games by a Reduction to SAT.In Proc.of the Workshop onGames in Design and Veriﬁcation,GDV’05,Edinburgh,Scotland,UK,2005.[6]M.Jurdzi´n ski.Deciding the winner in parity games is in UP∩rmationProcessing Letters,68(3):119–124,1998.[7]M.Jurdzi´n ski.Small progress measures for solving parity games.In Proc.of the17thAnnual Symposium on Theoretical Aspects of Computer Science,LNCS1770,pp.290–301,2000.[8] C.Stirling and D.Walker.Local Model Checking in the Modal Mu-Calculus.TCS89(1):161-177,1991.[9]W.Zielonka.Inﬁnite games onﬁnitely coloured graphs with applications to automata oninﬁnite trees.TCS200:135-183,1998.4。

课文参考译文 (14)-信息科学与电子工程专业英语(第2版)-吴雅婷-清华大学出版社

Unit 14 计算机和网络Unit 14-1第一部分：计算机的进展计算机和信息技术的进展计算机和信息技术的诞生可以追溯到许多世纪以前。

数学的发展引起了计算工具的发展。

据说17世纪法国的Blaise Pascal构建了第一台计算机。

在19世纪，常被推崇为计算之父的英国人Charles Babbage设计了第一台“分析机”。

该机器有一个机械的计算“工厂”，类似于19世纪早期的提花织布机，采用穿孔卡片来存储数字和处理要求。

Ada Lovelace和他（Charles Babbage）致力于设计并提出了指令序列的概念——程序。

到1871年Babbage逝世，这台机器还没有完成。

将近一个世纪以后，随着电子机械计算机的发展（程序）这一概念再次出现。

1890年，Herman Hollerith采用穿孔卡片帮助美国人口普查局分类信息。

与此同时，电报电话的发明为通信和真空管的发展奠定了基础。

这一电子器件能够用于存储二进制形式的信息，即开或关，1或0。

第一台数字电子计算机ENIAC（电子计数积分计算机，见图14.1）是为美国军队开发的，并于1946年完成。

普林斯顿的数学教授V on Neumann对（程序）这一概念作了进一步深入的研究，加入了存储计算机程序的思想。

这就是存储在计算机内存中的指令序列，计算机执行这些指令完成程序控制的任务。

图14.1 ENIAC：第一台数字化电子计算机从这一阶段开始，计算机和计算机编程技术迅速发展。

从真空管发展到晶体管，大大减小了机器（计算机）的尺寸和成本，并提高了可靠性。

接着，集成电路技术的出现又减小了计算机的尺寸（和成本）。

20世纪60年代，典型的计算机是基于晶体管的机器，价值50万美金，并需要一个大空调房和一名现场工程师。

现在相同性能的计算机只要2000美元，并且放在桌上（就可使用了）。

随着计算机越来越小，越来越便宜，计算速度也更快——通过叫做芯片的单个集成电路来实现。

微处理器和微型计算机的发展微型计算机随着集成电路（或芯片）技术的发展而发展。

ASME与EN13445分析区别

ASME与EN13445分析区别自从1914年ASME锅炉压力容器规范第一版问世以来，经过九十年的实践和不断修订，到本世纪初，欧盟颁布与压力设备指令（PED）配套EN 13445压力容器标准，犹如一声春雷，打破了世界压力容器规范的格局，形成两大权威规范并存的局面。

实际上，这是压力容器发展史上空前未有的一次大碰撞，它发出灿烂耀眼的火花。

碰撞是在压力容器的设计、材料、制造和检验多方面进行的，而主要是在设计方面，特别是在分析设计方面。

欧洲标准在披露ASME规范执行过程中遇到的棘手问题的同时，提出了他们的解决方案，在设计概念上出现了许多创新，ASME也发现其规范存在的若干不足，拨款立项，广泛征求使现行规范趋于现代化的建议。

这次大碰撞蕴育着今后压力容器设计概念的大的改革，我们必须拭目以待。

台湾著名企业家温世仁今年在北京召开的京台科技论坛上说：“从今年开始，我们要把这个论坛定位在制订两岸共同标准上，这个世界，最早的时候是生产力的竞争，后来是技术力的竞争，再过来就是所谓智慧财产权（即知识产权）的竞争。

再下来就是所谓标准之战。

未来的世界主要是标准之战。

”我国是压力容器生产大国，已能制造千吨级加氢反应器和一些核容器，已有一些压力容器出口欧美，但还不是压力容器生产强国，一些技术含量较高的压力设备还要进口。

我国压力容器标准在世界所占分额极小，我们必须在当今世界标准之战中占有一席之地。

实际上，支持标准的是包括专利在内的大量知识产权，没有知识产权的支撑，标准将苍白无力；而使标准真正起到作用，则是后续产业的强力支撑，没有后者，将无法证明标准是成功的。

据报导，截止2002年底，我国出口企业因技术壁垒引发的摩擦金额高达400多亿美元，占出口总额的30%，损失金额高达170亿美元（今年9月北京科博会2003年标准与专利北京国际论坛国家标委会有关人士透露）。

为了弄清国际贸易中的游戏规则，使我处于主动地位，我们必须认真研究当今世界压力容器标准之战中欧美两大标准体系的情况和他们对我们的影响。

C.parvum全基因组序列

DOI: 10.1126/science.1094786, 441 (2004);304Science et al.Mitchell S. Abrahamsen,Cryptosporidium parvum Complete Genome Sequence of the Apicomplexan, (this information is current as of October 7, 2009 ):The following resources related to this article are available online at/cgi/content/full/304/5669/441version of this article at:including high-resolution figures, can be found in the online Updated information and services,/cgi/content/full/1094786/DC1 can be found at:Supporting Online Material/cgi/content/full/304/5669/441#otherarticles , 9 of which can be accessed for free: cites 25 articles This article 239 article(s) on the ISI Web of Science. cited by This article has been /cgi/content/full/304/5669/441#otherarticles 53 articles hosted by HighWire Press; see: cited by This article has been/cgi/collection/genetics Genetics: subject collections This article appears in the following/about/permissions.dtl in whole or in part can be found at: this article permission to reproduce of this article or about obtaining reprints Information about obtaining registered trademark of AAAS.is a Science 2004 by the American Association for the Advancement of Science; all rights reserved. The title Copyright American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. 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Univ.Press,Cambridge,1996).11.Often word meanings can only be fully determined byinvokingworld knowledg e.For instance,the meaningof “ﬂat”in a“ﬂat road”implies the absence of holes.However,in the expression“aﬂat tire,”it indicates the presence of a hole.The meaningof“ﬁnish”in the phrase “Billﬁnished the book”implies that Bill completed readingthe book.However,the phrase“the g oatﬁn-ished the book”can only be interpreted as the goat eatingor destroyingthe book.The examples illustrate that word meaningis often underdetermined and nec-essarily intertwined with general world knowledge.In such cases,it is hard to see how the integration of lexical meaning and general world knowledge could be strictly separated(3,31).12.W.Marslen-Wilson,C.M.Brown,L.K.Tyler,Lang.Cognit.Process.3,1(1988).13.ERPs for30subjects were averaged time-locked to theonset of the critical words,with40items per condition.Sentences were presented word by word on the centerof a computer screen,with a stimulus onset 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Apicomplexan,Cryptosporidium parvumMitchell S.Abrahamsen,1,2*†Thomas J.Templeton,3†Shinichiro Enomoto,1Juan E.Abrahante,1Guan Zhu,4 Cheryl ncto,1Mingqi Deng,1Chang Liu,1‡Giovanni Widmer,5Saul Tzipori,5GregoryA.Buck,6Ping Xu,6 Alan T.Bankier,7Paul H.Dear,7Bernard A.Konfortov,7 Helen F.Spriggs,7Lakshminarayan Iyer,8Vivek Anantharaman,8L.Aravind,8Vivek Kapur2,9The apicomplexan Cryptosporidium parvum is an intestinal parasite that affects healthy humans and animals,and causes an unrelenting infection in immuno-compromised individuals such as AIDS patients.We report the complete ge-nome sequence of C.parvum,type II isolate.Genome analysis identiﬁes ex-tremely streamlined metabolic pathways and a reliance on the host for nu-trients.In contrast to Plasmodium and Toxoplasma,the parasite lacks an api-coplast and its genome,and possesses a degenerate mitochondrion that has lost its genome.Several novel classes of cell-surface and secreted proteins with a potential role in host interactions and pathogenesis were also detected.Elu-cidation of the core metabolism,including enzymes with high similarities to bacterial and plant counterparts,opens new avenues for drug development.Cryptosporidium parvum is a globally impor-tant intracellular pathogen of humans and animals.The duration of infection and patho-genesis of cryptosporidiosis depends on host immune status,ranging from a severe but self-limiting diarrhea in immunocompetent individuals to a life-threatening,prolonged infection in immunocompromised patients.Asubstantial degree of morbidity and mortalityis associated with infections in AIDS pa-tients.Despite intensive efforts over the past20years,there is currently no effective ther-apy for treating or preventing C.parvuminfection in humans.Cryptosporidium belongs to the phylumApicomplexa,whose members share a com-mon apical secretory apparatus mediating lo-comotion and tissue or cellular invasion.Many apicomplexans are of medical or vet-erinary importance,including Plasmodium,Babesia,Toxoplasma,Neosprora,Sarcocys-tis,Cyclospora,and Eimeria.The life cycle ofC.parvum is similar to that of other cyst-forming apicomplexans(e.g.,Eimeria and Tox-oplasma),resulting in the formation of oocysts1Department of Veterinary and Biomedical Science,College of Veterinary Medicine,2Biomedical Genom-ics Center,University of Minnesota,St.Paul,MN55108,USA.3Department of Microbiology and Immu-nology,Weill Medical College and Program in Immu-nology,Weill Graduate School of Medical Sciences ofCornell University,New York,NY10021,USA.4De-partment of Veterinary Pathobiology,College of Vet-erinary Medicine,Texas A&M University,College Sta-tion,TX77843,USA.5Division of Infectious Diseases,Tufts University School of Veterinary Medicine,NorthGrafton,MA01536,USA.6Center for the Study ofBiological Complexity and Department of Microbiol-ogy and Immunology,Virginia Commonwealth Uni-versity,Richmond,VA23198,USA.7MRC Laboratoryof Molecular Biology,Hills Road,Cambridge CB22QH,UK.8National Center for Biotechnology Infor-mation,National Library of Medicine,National Insti-tutes of Health,Bethesda,MD20894,USA.9Depart-ment of Microbiology,University of Minnesota,Min-neapolis,MN55455,USA.*To whom correspondence should be addressed.E-mail:abe@†These authors contributed equally to this work.‡Present address:Bioinformatics Division,Genetic Re-search,GlaxoSmithKline Pharmaceuticals,5MooreDrive,Research Triangle Park,NC27009,USA.R E P O R T S SCIENCE VOL30416APRIL2004441o n O c t o b e r 7 , 2 0 0 9 w w w . s c i e n c e m a g . o r g D o w n l o a d e d f r o mthat are shed in the feces of infected hosts.C.parvum oocysts are highly resistant to environ-mental stresses,including chlorine treatment of community water supplies;hence,the parasite is an important water-and food-borne pathogen (1).The obligate intracellular nature of the par-asite ’s life cycle and the inability to culture the parasite continuously in vitro greatly impair researchers ’ability to obtain purified samples of the different developmental stages.The par-asite cannot be genetically manipulated,and transformation methodologies are currently un-available.To begin to address these limitations,we have obtained the complete C.parvum ge-nome sequence and its predicted protein com-plement.(This whole-genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the project accession AAEE00000000.The version described in this paper is the first version,AAEE01000000.)The random shotgun approach was used to obtain the complete DNA sequence (2)of the Iowa “type II ”isolate of C.parvum .This isolate readily transmits disease among numerous mammals,including humans.The resulting ge-nome sequence has roughly 13ϫgenome cov-erage containing five gaps and 9.1Mb of totalDNA sequence within eight chromosomes.The C.parvum genome is thus quite compact rela-tive to the 23-Mb,14-chromosome genome of Plasmodium falciparum (3);this size difference is predominantly the result of shorter intergenic regions,fewer introns,and a smaller number of genes (Table 1).Comparison of the assembled sequence of chromosome VI to that of the recently published sequence of chromosome VI (4)revealed that our assembly contains an ad-ditional 160kb of sequence and a single gap versus two,with the common sequences dis-playing a 99.993%sequence identity (2).The relative paucity of introns greatly simplified gene predictions and facilitated an-notation (2)of predicted open reading frames (ORFs).These analyses provided an estimate of 3807protein-encoding genes for the C.parvum genome,far fewer than the estimated 5300genes predicted for the Plasmodium genome (3).This difference is primarily due to the absence of an apicoplast and mitochondrial genome,as well as the pres-ence of fewer genes encoding metabolic functions and variant surface proteins,such as the P.falciparum var and rifin molecules (Table 2).An analysis of the encoded pro-tein sequences with the program SEG (5)shows that these protein-encoding genes are not enriched in low-complexity se-quences (34%)to the extent observed in the proteins from Plasmodium (70%).Our sequence analysis indicates that Cryptosporidium ,unlike Plasmodium and Toxoplasma ,lacks both mitochondrion and apicoplast genomes.The overall complete-ness of the genome sequence,together with the fact that similar DNA extraction proce-dures used to isolate total genomic DNA from C.parvum efficiently yielded mito-chondrion and apicoplast genomes from Ei-meria sp.and Toxoplasma (6,7),indicates that the absence of organellar genomes was unlikely to have been the result of method-ological error.These conclusions are con-sistent with the absence of nuclear genes for the DNA replication and translation machinery characteristic of mitochondria and apicoplasts,and with the lack of mito-chondrial or apicoplast targeting signals for tRNA synthetases.A number of putative mitochondrial pro-teins were identified,including components of a mitochondrial protein import apparatus,chaperones,uncoupling proteins,and solute translocators (table S1).However,the ge-nome does not encode any Krebs cycle en-zymes,nor the components constituting the mitochondrial complexes I to IV;this finding indicates that the parasite does not rely on complete oxidation and respiratory chains for synthesizing adenosine triphosphate (ATP).Similar to Plasmodium ,no orthologs for the ␥,␦,or εsubunits or the c subunit of the F 0proton channel were detected (whereas all subunits were found for a V-type ATPase).Cryptosporidium ,like Eimeria (8)and Plas-modium ,possesses a pyridine nucleotide tran-shydrogenase integral membrane protein that may couple reduced nicotinamide adenine dinucleotide (NADH)and reduced nico-tinamide adenine dinucleotide phosphate (NADPH)redox to proton translocation across the inner mitochondrial membrane.Unlike Plasmodium ,the parasite has two copies of the pyridine nucleotide transhydrogenase gene.Also present is a likely mitochondrial membrane –associated,cyanide-resistant alter-native oxidase (AOX )that catalyzes the reduction of molecular oxygen by ubiquinol to produce H 2O,but not superoxide or H 2O 2.Several genes were identified as involved in biogenesis of iron-sulfur [Fe-S]complexes with potential mitochondrial targeting signals (e.g.,nifS,nifU,frataxin,and ferredoxin),supporting the presence of a limited electron flux in the mitochondrial remnant (table S2).Our sequence analysis confirms the absence of a plastid genome (7)and,additionally,the loss of plastid-associated metabolic pathways including the type II fatty acid synthases (FASs)and isoprenoid synthetic enzymes thatTable 1.General features of the C.parvum genome and comparison with other single-celled eukaryotes.Values are derived from respective genome project summaries (3,26–28).ND,not determined.FeatureC.parvum P.falciparum S.pombe S.cerevisiae E.cuniculiSize (Mbp)9.122.912.512.5 2.5(G ϩC)content (%)3019.43638.347No.of genes 38075268492957701997Mean gene length (bp)excluding introns 1795228314261424ND Gene density (bp per gene)23824338252820881256Percent coding75.352.657.570.590Genes with introns (%)553.9435ND Intergenic regions (G ϩC)content %23.913.632.435.145Mean length (bp)5661694952515129RNAsNo.of tRNA genes 454317429944No.of 5S rRNA genes 6330100–2003No.of 5.8S ,18S ,and 28S rRNA units 57200–400100–20022Table parison between predicted C.parvum and P.falciparum proteins.FeatureC.parvum P.falciparum *Common †Total predicted proteins380752681883Mitochondrial targeted/encoded 17(0.45%)246(4.7%)15Apicoplast targeted/encoded 0581(11.0%)0var/rif/stevor ‡0236(4.5%)0Annotated as protease §50(1.3%)31(0.59%)27Annotated as transporter ࿣69(1.8%)34(0.65%)34Assigned EC function ¶167(4.4%)389(7.4%)113Hypothetical proteins925(24.3%)3208(60.9%)126*Values indicated for P.falciparum are as reported (3)with the exception of those for proteins annotated as protease or transporter.†TBLASTN hits (e Ͻ–5)between C.parvum and P.falciparum .‡As reported in (3).§Pre-dicted proteins annotated as “protease or peptidase”for C.parvum (CryptoGenome database,)and P.falciparum (PlasmoDB database,).࿣Predicted proteins annotated as “trans-porter,permease of P-type ATPase”for C.parvum (CryptoGenome)and P.falciparum (PlasmoDB).¶Bidirectional BLAST hit (e Ͻ–15)to orthologs with assigned Enzyme Commission (EC)numbers.Does not include EC assignment numbers for protein kinases or protein phosphatases (due to inconsistent annotation across genomes),or DNA polymerases or RNA polymerases,as a result of issues related to subunit inclusion.(For consistency,46proteins were excluded from the reported P.falciparum values.)R E P O R T S16APRIL 2004VOL 304SCIENCE 442 o n O c t o b e r 7, 2009w w w .s c i e n c e m a g .o r g D o w n l o a d e d f r o mare otherwise localized to the plastid in other apicomplexans.C.parvum fatty acid biosynthe-sis appears to be cytoplasmic,conducted by a large(8252amino acids)modular type I FAS (9)and possibly by another large enzyme that is related to the multidomain bacterial polyketide synthase(10).Comprehensive screening of the C.parvum genome sequence also did not detect orthologs of Plasmodium nuclear-encoded genes that contain apicoplast-targeting and transit sequences(11).C.parvum metabolism is greatly stream-lined relative to that of Plasmodium,and in certain ways it is reminiscent of that of another obligate eukaryotic parasite,the microsporidian Encephalitozoon.The degeneration of the mi-tochondrion and associated metabolic capabili-ties suggests that the parasite largely relies on glycolysis for energy production.The parasite is capable of uptake and catabolism of mono-sugars(e.g.,glucose and fructose)as well as synthesis,storage,and catabolism of polysac-charides such as trehalose and amylopectin. Like many anaerobic organisms,it economizes ATP through the use of pyrophosphate-dependent phosphofructokinases.The conver-sion of pyruvate to acetyl–coenzyme A(CoA) is catalyzed by an atypical pyruvate-NADPH oxidoreductase(Cp PNO)that contains an N-terminal pyruvate–ferredoxin oxidoreductase (PFO)domain fused with a C-terminal NADPH–cytochrome P450reductase domain (CPR).Such a PFO-CPR fusion has previously been observed only in the euglenozoan protist Euglena gracilis(12).Acetyl-CoA can be con-verted to malonyl-CoA,an important precursor for fatty acid and polyketide biosynthesis.Gly-colysis leads to several possible organic end products,including lactate,acetate,and ethanol. The production of acetate from acetyl-CoA may be economically beneficial to the parasite via coupling with ATP production.Ethanol is potentially produced via two in-dependent pathways:(i)from the combination of pyruvate decarboxylase and alcohol dehy-drogenase,or(ii)from acetyl-CoA by means of a bifunctional dehydrogenase(adhE)with ac-etaldehyde and alcohol dehydrogenase activi-ties;adhE first converts acetyl-CoA to acetal-dehyde and then reduces the latter to ethanol. AdhE predominantly occurs in bacteria but has recently been identified in several protozoans, including vertebrate gut parasites such as Enta-moeba and Giardia(13,14).Adjacent to the adhE gene resides a second gene encoding only the AdhE C-terminal Fe-dependent alcohol de-hydrogenase domain.This gene product may form a multisubunit complex with AdhE,or it may function as an alternative alcohol dehydro-genase that is specific to certain growth condi-tions.C.parvum has a glycerol3-phosphate dehydrogenase similar to those of plants,fungi, and the kinetoplastid Trypanosoma,but(unlike trypanosomes)the parasite lacks an ortholog of glycerol kinase and thus this pathway does not yield glycerol production.In addition to themodular fatty acid synthase(Cp FAS1)andpolyketide synthase homolog(Cp PKS1), C.parvum possesses several fatty acyl–CoA syn-thases and a fatty acyl elongase that may partici-pate in fatty acid metabolism.Further,enzymesfor the metabolism of complex lipids(e.g.,glyc-erolipid and inositol phosphate)were identified inthe genome.Fatty acids are apparently not anenergy source,because enzymes of the fatty acidoxidative pathway are absent,with the exceptionof a3-hydroxyacyl-CoA dehydrogenase.C.parvum purine metabolism is greatlysimplified,retaining only an adenosine ki-nase and enzymes catalyzing conversionsof adenosine5Ј-monophosphate(AMP)toinosine,xanthosine,and guanosine5Ј-monophosphates(IMP,XMP,and GMP).Among these enzymes,IMP dehydrogenase(IMPDH)is phylogenetically related toε-proteobacterial IMPDH and is strikinglydifferent from its counterparts in both thehost and other apicomplexans(15).In con-trast to other apicomplexans such as Toxo-plasma gondii and P.falciparum,no geneencoding hypoxanthine-xanthineguaninephosphoribosyltransferase(HXGPRT)is de-tected,in contrast to a previous report on theactivity of this enzyme in C.parvum sporo-zoites(16).The absence of HXGPRT sug-gests that the parasite may rely solely on asingle enzyme system including IMPDH toproduce GMP from AMP.In contrast to otherapicomplexans,the parasite appears to relyon adenosine for purine salvage,a modelsupported by the identification of an adeno-sine transporter.Unlike other apicomplexansand many parasitic protists that can synthe-size pyrimidines de novo,C.parvum relies onpyrimidine salvage and retains the ability forinterconversions among uridine and cytidine5Ј-monophosphates(UMP and CMP),theirdeoxy forms(dUMP and dCMP),and dAMP,as well as their corresponding di-and triphos-phonucleotides.The parasite has also largelyshed the ability to synthesize amino acids denovo,although it retains the ability to convertselect amino acids,and instead appears torely on amino acid uptake from the host bymeans of a set of at least11amino acidtransporters(table S2).Most of the Cryptosporidium core pro-cesses involved in DNA replication,repair,transcription,and translation conform to thebasic eukaryotic blueprint(2).The transcrip-tional apparatus resembles Plasmodium interms of basal transcription machinery.How-ever,a striking numerical difference is seenin the complements of two RNA bindingdomains,Sm and RRM,between P.falcipa-rum(17and71domains,respectively)and C.parvum(9and51domains).This reductionresults in part from the loss of conservedproteins belonging to the spliceosomal ma-chinery,including all genes encoding Smdomain proteins belonging to the U6spliceo-somal particle,which suggests that this par-ticle activity is degenerate or entirely lost.This reduction in spliceosomal machinery isconsistent with the reduced number of pre-dicted introns in Cryptosporidium(5%)rela-tive to Plasmodium(Ͼ50%).In addition,keycomponents of the small RNA–mediatedposttranscriptional gene silencing system aremissing,such as the RNA-dependent RNApolymerase,Argonaute,and Dicer orthologs;hence,RNA interference–related technolo-gies are unlikely to be of much value intargeted disruption of genes in C.parvum.Cryptosporidium invasion of columnarbrush border epithelial cells has been de-scribed as“intracellular,but extracytoplas-mic,”as the parasite resides on the surface ofthe intestinal epithelium but lies underneaththe host cell membrane.This niche may al-low the parasite to evade immune surveil-lance but take advantage of solute transportacross the host microvillus membrane or theextensively convoluted parasitophorous vac-uole.Indeed,Cryptosporidium has numerousgenes(table S2)encoding families of putativesugar transporters(up to9genes)and aminoacid transporters(11genes).This is in starkcontrast to Plasmodium,which has fewersugar transporters and only one putative ami-no acid transporter(GenBank identificationnumber23612372).As a first step toward identification ofmulti–drug-resistant pumps,the genome se-quence was analyzed for all occurrences ofgenes encoding multitransmembrane proteins.Notable are a set of four paralogous proteinsthat belong to the sbmA family(table S2)thatare involved in the transport of peptide antibi-otics in bacteria.A putative ortholog of thePlasmodium chloroquine resistance–linkedgene Pf CRT(17)was also identified,althoughthe parasite does not possess a food vacuole likethe one seen in Plasmodium.Unlike Plasmodium,C.parvum does notpossess extensive subtelomeric clusters of anti-genically variant proteins(exemplified by thelarge families of var and rif/stevor genes)thatare involved in immune evasion.In contrast,more than20genes were identified that encodemucin-like proteins(18,19)having hallmarksof extensive Thr or Ser stretches suggestive ofglycosylation and signal peptide sequences sug-gesting secretion(table S2).One notable exam-ple is an11,700–amino acid protein with anuninterrupted stretch of308Thr residues(cgd3_720).Although large families of secretedproteins analogous to the Plasmodium multi-gene families were not found,several smallermultigene clusters were observed that encodepredicted secreted proteins,with no detectablesimilarity to proteins from other organisms(Fig.1,A and B).Within this group,at leastfour distinct families appear to have emergedthrough gene expansions specific to the Cryp-R E P O R T S SCIENCE VOL30416APRIL2004443o n O c t o b e r 7 , 2 0 0 9 w w w . s c i e n c e m a g . o r g D o w n l o a d e d f r o mtosporidium clade.These families —SKSR,MEDLE,WYLE,FGLN,and GGC —were named after well-conserved sequence motifs (table S2).Reverse transcription polymerase chain reaction (RT-PCR)expression analysis (20)of one cluster,a locus of seven adjacent CpLSP genes (Fig.1B),shows coexpression during the course of in vitro development (Fig.1C).An additional eight genes were identified that encode proteins having a periodic cysteine structure similar to the Cryptosporidium oocyst wall protein;these eight genes are similarly expressed during the onset of oocyst formation and likely participate in the formation of the coccidian rigid oocyst wall in both Cryptospo-ridium and Toxoplasma (21).Whereas the extracellular proteins described above are of apparent apicomplexan or lineage-specific in-vention,Cryptosporidium possesses many genesencodingsecretedproteinshavinglineage-specific multidomain architectures composed of animal-and bacterial-like extracellular adhe-sive domains (fig.S1).Lineage-specific expansions were ob-served for several proteases (table S2),in-cluding an aspartyl protease (six genes),a subtilisin-like protease,a cryptopain-like cys-teine protease (five genes),and a Plas-modium falcilysin-like (insulin degrading enzyme –like)protease (19genes).Nine of the Cryptosporidium falcilysin genes lack the Zn-chelating “HXXEH ”active site motif and are likely to be catalytically inactive copies that may have been reused for specific protein-protein interactions on the cell sur-face.In contrast to the Plasmodium falcilysin,the Cryptosporidium genes possess signal peptide sequences and are likely trafficked to a secretory pathway.The expansion of this family suggests either that the proteins have distinct cleavage specificities or that their diversity may be related to evasion of a host immune response.Completion of the C.parvum genome se-quence has highlighted the lack of conven-tional drug targets currently pursued for the control and treatment of other parasitic protists.On the basis of molecular and bio-chemical studies and drug screening of other apicomplexans,several putative Cryptospo-ridium metabolic pathways or enzymes have been erroneously proposed to be potential drug targets (22),including the apicoplast and its associated metabolic pathways,the shikimate pathway,the mannitol cycle,the electron transport chain,and HXGPRT.Nonetheless,complete genome sequence analysis identifies a number of classic and novel molecular candidates for drug explora-tion,including numerous plant-like and bacterial-like enzymes (tables S3and S4).Although the C.parvum genome lacks HXGPRT,a potent drug target in other api-complexans,it has only the single pathway dependent on IMPDH to convert AMP to GMP.The bacterial-type IMPDH may be a promising target because it differs substan-tially from that of eukaryotic enzymes (15).Because of the lack of de novo biosynthetic capacity for purines,pyrimidines,and amino acids,C.parvum relies solely on scavenge from the host via a series of transporters,which may be exploited for chemotherapy.C.parvum possesses a bacterial-type thymidine kinase,and the role of this enzyme in pyrim-idine metabolism and its drug target candida-cy should be pursued.The presence of an alternative oxidase,likely targeted to the remnant mitochondrion,gives promise to the study of salicylhydroxamic acid (SHAM),as-cofuranone,and their analogs as inhibitors of energy metabolism in the parasite (23).Cryptosporidium possesses at least 15“plant-like ”enzymes that are either absent in or highly divergent from those typically found in mammals (table S3).Within the glycolytic pathway,the plant-like PPi-PFK has been shown to be a potential target in other parasites including T.gondii ,and PEPCL and PGI ap-pear to be plant-type enzymes in C.parvum .Another example is a trehalose-6-phosphate synthase/phosphatase catalyzing trehalose bio-synthesis from glucose-6-phosphate and uridine diphosphate –glucose.Trehalose may serve as a sugar storage source or may function as an antidesiccant,antioxidant,or protein stability agent in oocysts,playing a role similar to that of mannitol in Eimeria oocysts (24).Orthologs of putative Eimeria mannitol synthesis enzymes were not found.However,two oxidoreductases (table S2)were identified in C.parvum ,one of which belongs to the same families as the plant mannose dehydrogenases (25)and the other to the plant cinnamyl alcohol dehydrogenases.In principle,these enzymes could synthesize protective polyol compounds,and the former enzyme could use host-derived mannose to syn-thesize mannitol.References and Notes1.D.G.Korich et al .,Appl.Environ.Microbiol.56,1423(1990).2.See supportingdata on Science Online.3.M.J.Gardner et al .,Nature 419,498(2002).4.A.T.Bankier et al .,Genome Res.13,1787(2003).5.J.C.Wootton,Comput.Chem.18,269(1994).Fig.1.(A )Schematic showing the chromosomal locations of clusters of potentially secreted proteins.Numbers of adjacent genes are indicated in paren-theses.Arrows indicate direc-tion of clusters containinguni-directional genes (encoded on the same strand);squares indi-cate clusters containingg enes encoded on both strands.Non-paralogous genes are indicated by solid gray squares or direc-tional triangles;SKSR (green triangles),FGLN (red trian-gles),and MEDLE (blue trian-gles)indicate three C.parvum –speciﬁc families of paralogous genes predominantly located at telomeres.Insl (yellow tri-angles)indicates an insulinase/falcilysin-like paralogous gene family.Cp LSP (white square)indicates the location of a clus-ter of adjacent large secreted proteins (table S2)that are cotranscriptionally regulated.Identiﬁed anchored telomeric repeat sequences are indicated by circles.(B )Schematic show-inga select locus containinga cluster of coexpressed large secreted proteins (Cp LSP).Genes and intergenic regions (regions between identiﬁed genes)are drawn to scale at the nucleotide level.The length of the intergenic re-gions is indicated above or be-low the locus.(C )Relative ex-pression levels of CpLSP (red lines)and,as a control,C.parvum Hedgehog-type HINT domain gene (blue line)duringin vitro development,as determined by semiquantitative RT-PCR usingg ene-speciﬁc primers correspondingto the seven adjacent g enes within the CpLSP locus as shown in (B).Expression levels from three independent time-course experiments are represented as the ratio of the expression of each gene to that of C.parvum 18S rRNA present in each of the infected samples (20).R E P O R T S16APRIL 2004VOL 304SCIENCE 444 o n O c t o b e r 7, 2009w w w .s c i e n c e m a g .o r g D o w n l o a d e d f r o m。

HarmonizingTradi...

Harmonizing Traditional Chinese and Modern Western Medicine: A Perspective from the USKa Kit Hui, M.D., F.A.C.P.Professor, Department of Medicine, UCLA School of Medicine; Director, UCLA Center for East-West MedicineThe current interest in traditional and complementary medicine in the United States is attracting attention in many parts of the community - the health care industry, governmental agencies, media and the public.1 An increasing number of insurers and managed care organizations are providing benefits for traditional medicine, a majority of U.S. medical schools now offer courses covering traditional medicine,2,3 and, as Eisenberg’s national studies have revealed, more people are using complementary therapies.4,5 To facilitate research on the effectiveness of alternative therapies, the National Center for Complementary and Alternative Medicine (NCCAM) received a budget of $50 million in 1999. Recognizing the need to encourage quality and quantity of scientific information on botanicals, as well as develop a systematic evaluation of safety and efficacy of dietary supplements, two research centers were also established this year to investigate the biological effects of botanicals.6Many patients are using traditional and modern medical paradigms concurrently, creating a need for the appropriate and smooth merger of the two medicines. The theories and techniques of traditional Chinese medicine (TCM) encompass most practices classified as complementary medicine in the United States, and have become increasingly important in the health care system.7 Traditional Chinese medicine is affordable, low tech, safe and effective when used appropriately. Ongoing research around the world on acupuncture, herbs, massage8,9 and Tai-Chi10,11 have shed light on some of the theories and practices of TCM. Evidence derived from vigorous research design12 as well as patient demand are fueling the merger of TCM with modern medicine at the clinical level, while more academic researchers and institutions are becoming more interested in the potential of integrating these two healing traditions. AcupunctureBased on evidence reviewed during the 1997 NIH Consensus Conference, the NIH Consensus Development Panel conservatively recommended that acupuncture may be used as an adjunct treatment, an alternative, or part of a comprehensive management program for a number of conditions. The panel ascertained that acupuncture can be used to treat post-operative and chemotherapy induced nausea and vomiting, as well as post-operative dental pain. It was also recommended as an adjunct treatment or an acceptable alternative for addiction, stroke rehabilitation, headache, menstrual cramps, tennis elbow, fibromyalgia, myofacial pain, osteoarthritis, low back pain, carpal tunnel syndrome, and asthma.13Future clinical trials that test acupuncture within the framework of traditional Chinese medicine are likely to provide a more appropriate and clinically meaningful assessment of acupuncture efficacy than the current generation of clinical trials which use a diagnosis framed primarily in biomedical terms. The scientific rigor of current research must continue; however, the NIH approach towards data analysis is too strict and limits potentially useful indications. Unlike drugs, acupuncture is more akin to surgery and physical therapy in terms of therapeuticmodalities. Hence, the evaluation of evidence for efficacy in acupuncture ought to be similar to these therapeutic interventions. For the time being, evidence based on large case series should be considered in determining recommendations for clinical practice while evidence derived from more vigorous research designs are being carried out.In elucidating the mechanisms of acupuncture and exploring its role in a variety of situations, innovative techniques such as fMRI (functional magnetic resonance imaging),14 PET (positron emission tomography), SPECT (single photon emission computer tomography), and MEG (magnetoencephalography) are beginning to be utilized. Studies on acupuncture in terms of its neuroanatomic and neurophysiological bases, bioelectrical properties, analgesia effects, and its role in regulation in areas such as gastrointestinal, immunological and cardiovascular functions are being carried out. More intense research with increased funding and scientific vigor, in an out of the US, will likely uncover additional areas where acupuncture may prove useful. This will further drive the adoption of acupuncture as a common therapeutic modality, not only in treatment, but also in prevention of disease and promotion of wellness. With technological advancement, innovative methods of acupuncture point stimulation will continue to be explored and perfected. Basic research on acupuncture will also help facilitate improved understanding of neuroscience and other aspects of human physiology and function.Because of heightened patient demand and better understanding of the role of acupuncture in health care through research and clinical experience, the biomedical establishment, health insurance industries, physicians and other health care providers are beginning to take an interest in acupuncture. In time, those who do not embrace acupuncture will be at a disadvantage. As the efficacy and cost saving potential of acupuncture is more widely recognized, there will be an even stronger push for more insurance companies, medical groups, and even Medicare to provide coverage of acupuncture treatment. We will witness acupuncture being utilized increasingly in outpatient settings, hospitals, rehabilitation units and hospices. An increasing number of physician acupuncturists as well as non-physician acupuncturists are working in different clinical settings. Some licensed acupuncturist specialists will work side by side with MDs in specialized areas.In the new millennium, the practice of acupuncture will be guided not only by traditional Chinese medicine concepts, but also by data generated through research advances in diverse fields such as neuroscience, molecular biology, chronobiology, computer and information science, energetics, integrative physiology and innovative clinical trial methodology.Herbs*Humans and animals have tested and used botanicals to relieve their suffering since ancient times. The appropriate use of Chinese herbs requires proper TCM diagnosis of the zheng (pathophysiological pattern) of the patient, correct selection of the corresponding therapeutic strategies and principles that guide the choice of herbs and herbal formulas. When appropriately prepared and used, herbs can be safe and effective. However, when used without proper guidance, a wide array of complications may result.* Modified from Hui, K.K. “Summary and Conclusions” (1999). Botanical Medicine: Efficacy, Quality Assurance, and Regulation. Eskinazi, D. (ed.) New York: Mary Ann Liebert, Inc.15Modern scientific investigations on plant-based medicine have been carried out in many parts of the world, including clinical trials of botanical combination products. Clinical research methodologists should take the theoretical construct and clinical approach of TCM into consideration when designing trials. Research designs such as randomized controlled trials have advantages and disadvantages in determining the efficacy of any therapeutic intervention, and can be carried out for botanicals, as seen by a study on herbal formulas for irritable bowel syndrome.16 Yet, we should seek approaches other than conducting a clinical trial for each product to evaluate safety and efficacy. Alternatives to RCTs include quasi-experiments, cohort studies, case-control studies, and “N = 1” trials. These methods have their advantages and limitations but may be more suited to the evaluation of herbal efficacy. The accurate measures of patient-centered outcomes both generic and disease-specific are important regardless of the design of the study. Above all, the appropriate study design depends on the research question and hypothesis being tested.Evaluating evidence is both difficult and subjective. The synthesis of evidence is completely dependent on the completeness of the literature search, which is often not available for foreign studies, as well as the accuracy of evaluation. Also, there are situations when neither RCTs nor database analyses separately can answer the question of interest due to different populations being used in the various kinds of studies. Consensus in the real world of health care often requires using information that is less stringent than so-called hard data. Realizing this, we should recognize the research and practice of herbal therapies in China, Korea and Japan when making recommendations for clinical practice. The pharmacological basis for many herbs have been determined in these studies and, as long as safety is assured, their findings should be considered when making recommendations. It is essential that researchers and practitioners be educated in both traditional and western medicines in order to perform research appropriately and treat patients effectively.Integrative East-West MedicineHarmonizing traditional medicine and modern medicine is more than utilizing modern research design or scientific technology to assess traditional medicine; it should include assessment of the intrinsic value of traditional medicine in society. Political, economic and social factors play as equally an important role as research and education in the eventual blending of the two healing traditions.On the clinical level, blending involves the integration of the concepts and techniques of the two systems -- modern medicine’s analytical, quantitative, mechanistic approach with the systemic, holistic, individualistic approach of TCM. This framework is applied through the process of diagnosis, prevention, treatment, and rehabilitation and guides the use of the appropriate techniques, allowing the strengths of TCM to compensate for the weaknesses of modern western medicine. As our graying society falls victim to an increasing number of chronic illnesses, we need a health paradigm that solves problems and provides affordable, effective health care for all. We believe that integrative East-West medicine is a candidate for such a model of medicine.References1.Workshop on Alternative Medicine, Alternative Medicine: Expanding Medical Horizons, AReport to the National Institutes of Health on Alternative Medical Systems and Practices in the United States, 1992.2.Wetzel, M.S., Eisenberg, D.M., and Kaptchuk, T.J. (1998) Courses involving complementaryand alternative medicine at U.S. medical schools. JAMA, 280, 784-787.3.Hui, K.K., Yu, J., and Zylowska L. (in press) An innovative approach to teaching integrativeEast-West medicine to medical students and clinicians.4.Eisenberg, D.M., Foster, C., Kessler, R.C., et al. (1993) Unconventional medicine in theUnited States. N Engl J Med., 328, 246-252.5.Eisenberg, D.M., Davis, R.B., Ettner, S.L., Appel, S., Wilkey, S., Van Rompay, M., andKessler, R.C. (1998) Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. The Journal of American Medical Association, 280(18), 1569-1575.6.NIH (1999) Centers for dietary supplements research: botanicals [Internet] Available from:</grants/guide/rfa-files/RFA-OD-99-007.html> [Accessed March 23, 1999].7.Hui, K.K., Yu, J., and Zylowska L. (in press) The Progress of Chinese Medicine in the USA,The Way Forward for Chinese Medicine. Chan K and Lee H (eds.), Netherlands: Harwood Academic Publishers8.Field, T., Henteleff, T., Hernandez-Reif, M., Marting, E., Mavunda, K., Kuhn, C., andSchanberg, S. (1997b) Children with asthma have improved pulmonary functions after massage therapy. Journal of Pediatrics, 132, 854-858.9.Sunshine, W., Field, T., Schanberg, S., Quintino, O., Kilmer, T., Fierro, K., Burman, I.,Hashimoto, M., McBride, C., and Henteleff, T. (1996) Massage therapy and transcutaneous electrical stimulation effects on fibromyalgia. Journal of Clinical Rheumatology, 2, 18-22. 10.Wolf, S.L., Barnhart, H.X., Kutner, N.G., McNeely, E., Coogler, C., and Xu, T. (1996)Reducing frailty and falls in older persons: An investigation of Tai Chi and computerized balance training. Journal of the American Geriatrics Society, 44(5), 489-497.11.Young, D.R., Appel, L.J., Jee, S., and Miller, E.R. 3rd. (1999) The effects of aerobic exerciseand Tai Chi on blood pressure in older people: results of a randomized trial. Journal of the American Geriatrics Society, 47(3), 277-284.12.Spencer, J.W., Jacobs, J.J. (1999). Complementary/Alternative Medicine: An Evidence-BasedApproach. Missouri: Mary Ann Liebert, Inc.13.NIH Consensus Conference (1998) Acupuncture. JAMA, 280(17), 1518-1524.14.Cho, Z.H., Chung, S.C., Jones, J.P., Park, H.J., Wong, E.K., and Min, B.I. (1998) Newfindings of the correlation between acupoints and corresponding brain cortices using functional MRI. Proc. Natl. Acad. Sci., 95, 2670-2673.15.Hui, K.K. “Summary and Conclusions” (1999). Botanical Medicine: Efficacy, QualityAssurance, and Regulation. Eskinazi, D. (ed.) New York: Mary Ann Liebert, Inc., p. 79. 16.Bensoussan, A., Talley, N.J., Hing, M., et. al. (1998) Treatment of irritable bowel syndromewith Chinese herbal medicine: a randomized controlled trial. The Journal of American Medical Association, 280(18), 1585-1589.。

concept_01 (Introduction)

Date 1974 1979 1982 1985 1989 1993 1997 1999 2000 2004
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/products/processor/index.htm?iid=prod+prod_processor
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ASCA 2008-2009 (Mr. Yu)
1.1 E. Computing Now and Future
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• Nowadays, computer systems come in a variety of sizes, shapes and computing capabilities, from the smallest handheld personal digital assistant (PDA) to the largest multiple-CPU mainframe for the enterprise. • The trends of computing are smaller, faster, more reliable, lower in cost, easier to maintain, and more interconnected within computer networks.
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-- smaller in size (portable) -- single user -- responds to requests (e.g. sharing) -- support hundreds or thousands users -- handle complex tasks

《科技英语阅读》课后名词解释和翻译

Unit1 mathematics名词解释绝对补集absolute complement / 代数algebra /代数式algebraic expression / 代数方程algebraic equation / 代数不等式algebraic inequality / 任意常数arbitrary constant / 数组array / 底数；基数base number / 连续函数continuous function / 函数function / 复合函数function of function / 函数记号functional notation / 集合aggregate / 子集subset /迭代函数iterative function/优先权之争priority battle/分形特征fractal properties/有意义make sense/以越来越小的规模重复同一模式patterns repeat themselves at smaller and smaller scales/混沌理论chaos theory/季刊a quarterly journal/数学界the mathematics community/波纹线crisp lines/会议公报proceedings of a conference翻译3. Translate the sentences into Chinese.1)他主要是因为用分形这个概念来描述（海岸线、雪花、山脉和树木）等不规则形状等现象而闻名于世，这些不规则形状在越来越小的规模上不断重复同一模式。

2)如果再仔细观察，就可以发现集的边界并没有呈波纹线，而是像火焰一样闪光。

3)但是，克朗兹在这场辩论中引入了一个新东西，他说曼德布洛特集不是曼德布洛特集发明的，而是早在“曼德布洛特集”这个术语出现几年以前就已经明确地在数学文献中出现了。

4)曼德布洛特同时也暗示即使布鲁克斯和马特尔斯基的论文先于他发表，但因为他们没有领会到其价值，仍然不能将他们看作是曼德布洛特集的发现者。

PrimaryMetaphorandComplexMetaphor（NAI-gagfactory

University of Zurich/Swiss Federal Institute of Technology ZurichSeminar «Natural and Artiﬁcial Intelligence»Prof. Rolf Pfeifer (Uni ZH)/Prof. Elmar Holenstein (ETHZ) Primary Metaphor and Complex MetaphorNathan Labhart $Wartauweg 19CH–8049 ZürichSwitzerland********************079 478 97 66Major: Public Communications1st Minor: Computer Science2nd Minor: Computational LinguisticsFebruary 2002Contents Abstract (1)1What Does «Metaphor» Mean? (1)2Primary Metaphor (2)3Complex Metaphor (4)4What Are Metaphors Good For? (6)5How Is The Metaphor Theory Related To Cognitive Science? (6)References (7)Appendix A: Notation (8)AbstractThis text is a recapitulation of the seminar lecture held on November 8, 2001 about «Primary Metaphor and Complex Metaphor». Its purpose is to serve as a (belated) handout as well as a simple introduction to the Metaphor Theory as presented and applied in Lakoff/Johnson 1999 and, to a lesser extent, Lakoff/Núñez 2000.Some aspects of the original Metaphor Theory have been simpliﬁed or omitted not only in order to keep this text short, but also because they seem rather fuzzy and therefore do not really aid in understanding this theory.1What Does «Metaphor» Mean?In everyday language, «metaphor» is used mainly as a purely linguistic concept. According to Webster’s New Encyclopedic Dictionary, a metaphor is «a ﬁgure of speech in which a word or phrase denoting one kind of object or idea is used in place of another to suggest a similarity between them (as in the ship plows the sea).»Therefore, one would think that it is very easy to live happily without metaphors. The research by Lakoff and Johnson, however, shows that quite the opposite is true: Whatever we think, say, or do is heavily inﬂuenced by metaphors – yet it is true that Lakoff/Johnson use this expression in a less limited way. They apply the term meta-phor not only to linguistic phenomena but also to the «mental processes» which un-derly every utterance, action, or perception1. These processes structure our life down to the tiniest details, therefore it seems reasonable to say that without metaphors, our lifes would be quite difﬁcult.To give an example of how a metaphorical concept inﬂuences both language and action, let’s have a look at the term «argument». We might associate the following expressions with «argument»:·Your claims are indefensible.·He attacked every weak point in my argument.·His criticisms were right on target.1 However, since the majority of these processes are unconscious mechanisms which take place without our noticing them (and, even more important, without any scientiﬁc means to precisely measure or control them, at least for the time being), this seems to be a weak point in Lakoff and Johnson’s argumentation.·I demolished his argument.·I’ve never won an argument with him.·You disagree? Okay, shoot!·If you use that strategy, he’ll wipe you out.·He shot down all of my arguments.According to Lakoff and Johnson, the underlying metaphor which determines our thinking pattern when we reason about an argument, is «Argument Is War» (see Appendix A for notation conventions). Obviously, an argument can be compared toa ﬁght with words, a verbal battle. When carrying on an argument, we may even act in a war-like fashion: we gesticulate, shout at the opponent, and in the end, if we get carried away, we may even start hitting each other – and after the argument, we feel like the winner (or loser).Lakoff/Johnson also use this example to show that some metaphors are woven intoa certain cultural context. Imagine a society where an argument is thought of as a dance rather than a war: The goal of an argument might not be to win but to achieve a well-balanced, aesthetical way of discussing. The participants would have quite dif-ferent feelings about arguing; however, we might not recognize an argument as such because we don’t associate dancing with arguing.Note that a metaphor can be understood as a mapping function from a Source Domain into a Target Domain. In the example above, «War» is the Source Domain and «Argu-ment» is the Target Domain.2Primary MetaphorWe are able to reason about highly complex and abstract things like importance, similarity, or morality without noticeable effort. According to Lakoff and Johnson, we achieve this using metaphors, i.e. concepts from other domains of our (embodied, sen-sorimotor) experience – we literally «grasp» an abstract idea. But how does this meta-phorical thinking work?Compiling the research work of other cognitive scientists, Lakoff/Johnson hope to ex-plain the metaphorical mechanisms with the Integrated Theory of Primary Metaphor, which consists of four parts:·Johnson’s Theory of Conﬂation·Grady’s Theory of Primary Metaphor·Narayanan’s Neural Theory of Metaphor·Fauconnier and Turner’s Theory of Conceptual BlendingChristopher Johnson’s Theory of Conﬂation states that connections between subjective emotions and sensorimotor experiences develop during early childhood. For example, affection is typically correlated with the warmth of being held – an infant repeatedly feels the emotion and the sensorimotor experiences at the same time, which leads to conﬂation or «undifferentiated experience». During a later phase of differentiation, the two domains (affection and warmth) that have been linked together are separated out, but the cross-domain associations persist and form the mechanisms for metaphorical mapping. These metaphors are called Primary Metaphors. In the example, the child would think of affection in terms of warmth as in «a warm smile». Another example is «a close friend», where there exists a metaphorical mapping from the domain of affec-tion to the domain of the sensorimotor experience of being held closely to a person.Joe Grady’s Theory of Primary Metaphor states that Complex Metaphors (see chapter 3) are «molecular» constructions of «atomic» parts, the Primary Metaphors. The con-struction process is called conceptual blending and is further explained in its proper theory by Fauconnier and Turner (see below).Srini Narayanan’s Neural Theory of Metaphor explains that the associations created during the phase of conﬂation are actual neural connections between the involved brain regions.Gilles Fauconnier and Mark Turner’s Theory of Conceptual Blending states that dis-tinct domains can be coactivated (similar to Johnson’s Theory of Conﬂation) and that under certain conditions new cross-domain associations can be established. Thus, novel «blends» of previously separate metaphorical domains come into existence: this is the creation of Complex Metaphors.As a simpliﬁed example, the conﬂated experiences a young child has when big things, e.g. the parents, dominate the ﬁeld of vision or exert major forces (and are therefore recognized as being important), lead to neural connections between the brain regions for «importance» and «size». These physical associations persist even after childhood and are responsible for the Primary Metaphor «Important Is Big», which we use e.g.in the expression «Tomorrow is my big day».It should be clear now that Primary Metaphors are highly embodied. They depend di-rectly on our interaction with the environment and the shape of our body. We acquire Primary Metaphors automatically and unconsciously, simply by interacting with the world.This does not rule out the existence of non-metaphorical concepts, however. We use a vast system of literal concepts like Spatial-Relations Concepts2. All basic sensorimotor concepts are literal. Even concepts of subjective perception can be literal: for example, «these colors are similar» is literal, while «these colors are close» is metaphorical.3Complex MetaphorAccording to Grady’s theory, Primary Metaphors can be combined to larger structures, the so-called Complex Metaphors. Most of these «molecular» structures are stable and therefore determine an important part of our conceptual system. Thus, whatever we think, say, or do, is inﬂuenced by Complex Metaphors – they even structure our dreams.As an example, let us have a closer look at the Complex Metaphor «A Purposeful Life Is A Journey». In our culture, a person is supposed to have a purpose in life. One who cannot give his life a proper meaning seems lost or without direction, he doesn’t know where to turn. The structure of the Complex Metaphor «A Purposeful Life Is A Jour-ney» can be described as consisting of·Primary Metaphors: Purposes Are Destinations, Actions Are Motions·Cultural Belief: People are supposed to have purposes in life, and they should act so as to achieve those purposes.The metaphorical version of the Cultural Belief is·People are supposed to have destinations in life, and they should move in such a way as to reach these destinations.Combined with the fact that· A trip to a series of destinations is a journey,2 as explained by Raphael Bianchi in his presentation on «The Cognitive Unconscious and the Embodied Mind», November 1, 2001.these two Primary Metaphors and the Cultural Belief result in a Complex Metaphor (consisting of four sub-metaphors):· A Purposeful Life Is A Journey· A Person Living A Life Is A Traveler·Life Goals Are Destinations· A Life Plan Is An ItineraryThis metaphorical mapping allows us to reason about life (which can be rather difﬁ-cult) in terms of traveling, making it easier to grasp: Just as a journey requires an itinerary, a purposeful life needs to be planned carefully; there may be obstacles(difﬁculties) in the way (of life), which need to be avoided or removed; one should always know where he/she stands (in life); etc.Note that most Complex Metaphors cannot be «proven» experimentally, e.g. that there is no direct connection between a purposeful life and a journey. Does this mean that there is no grounding for this metaphorical mapping? No, because it is constructed of Primary Metaphors which are grounded. This demonstrates an important property of Complex Metaphors: The grounding of the whole is the grounding of its parts. Complex Metaphors can be composed not only of Primary Metaphors, but also of other Complex Metaphors. For example, there is a «Love Is A Journey» Metaphor, which is constructed similarly to the «A Purposeful Life Is A Journey» Metaphor. It consists of the following metaphorical mappings:·Love Is A Journey·Lovers Are Travelers·Their Common Life Goals Are Destinations· A Relationship Is A Vehicle (this is a Complex Metaphor, which consists of the Primary Metaphors «A Relationship Is An Enclosure» and «Intimacy Is Closeness»)·Difﬁculties Are Obstacles To MotionThis Complex Metaphor can be found in expressions like «look how far we’ve come»,«we can’t turn back now», «the relationship is not going anywhere» or «we may have to go our separate ways».4What Are Metaphors Good For?Probably the most essential thing about conceptual metaphors is their importance for reasoning. The example «Love Is A Journey» allows us not only to simply map words from the Source Domain «Journey» to the Target Domain «Love», but also to reason about love using concepts from the world of traveling.In addition, we are able to quickly understand novel expressions thanks to this mech-anism. When we encounter a song lyric such as «We’re driving in the fast lane on the freeway of love», we have an instantaneous feeling of understanding this rather ab-stract image. (Uncousciously) using the «Love Is A Journey» Metaphor, we may come to the following «translation» of the song lyric: Lovers in a love relationship make a lot of progress in a short time, and even though there may be the danger of wreckage and getting hurt, the speed of the relationship is stimulating. This shows that novel meta-phors can use the same mapping mechanism as previously established Complex Meta-phors.Metaphors also help us understand idiomatic expressions like spinning one’s wheels or off the track – unlike traditional linguistics, which has treated idioms as random com-binations of expressions, Metaphor Theory shows that idioms are systematically moti-vated by metaphorical mapping and certain conventional images.5How Is The Metaphor Theory Related To Cognitive Science?Not all Cognitive Scientists accept the Metaphor Theory. Many stick to the traditional opinion that concepts are not metaphorical but literal, and disembodied rather than embodied. Therefore they reject the assumptions made by Lakoff and Johnson.Some postmodern philosophers even deny that Cognitive Science can have results which build a foundation for criticizing particular philosophical views. According to them, Cognitive Science can be the basis neither for critique nor for alternative theo-ries. Lakoff/Johnson try to counter these reproaches by embedding the Metaphor Theory into existing theories.There are two main approaches to Cognitive Science:·First Generation (established in the 1950s and 1960s)·Second Generation (evolved in the mid-1970s)Cognitive Science of the First Generation is all about «Thinking = Symbol Manipula-tion». Symbols are internal representations of objects of the external world. The mind is understood as some kind of abstract computer program that happened to be execu-ted by the brain, but could very well be run on another «device». Thus, First Genera-tion Cognitive Science is based on a priori assumptions like Functionalism (disembo-died mind) and Literal Meaning.On the opposite side, there is Cognitive Science of the Second Generation which states that the mind is highly embodied and sensorimotor inﬂuence is central for reasoning. Lakoff and Johnson criticize the Cognitive Science of the First Generation for its many inadequacies. For example, it doesn’t rely on empirical evidence. The disem-bodied approach creates an unbridgeable gap between «objects» which are «out there», and subjectivity, which is «in here». This separation is an artiﬁcial construct, for we are never separated from reality. Therefore, Lakoff/Johnson adhere to the Second Generation of Cognitive Science, because its foundations are not a priori assumptions but empirical evidence.ReferencesLakoff, G. and Johnson, M. (1980). Metaphors We Live By.Chicago/London: The University of Chicago Press. [ISBN 0-226-46801-1]Lakoff, G. and Johnson, M. (1999). Philosophy in the Flesh: The Embodied Mindand Its Challenge to Western Thought.New York, NY: Basic Books. [ISBN 0-465-05674-1]Lakoff, G. and Núñez, R. E. (2000). Where Mathematics Comes From:How the Embodied Mind Brings Mathematics into Being.New York, NY: Basic Books. [ISBN 0-465-03771-2]Webster’s New Encyclopedic Dictionary (1995). New York, NY:Black Dog & Leventhal Publishers Inc. [ISBN 1-884822-20-7]Appendix A: NotationTo simplify things, Lakoff/Johnson propose and use the following two conventions for labeling and describing metaphors:·the form of a regular sentence (Similarity Is Closeness) when used as the name of the metaphorical mapping·the form of a mapping function (Closeness ¡ Similarity) when the metaphor’s structure is stressedNote the reversed order of Source and Target Domains.Appendix B: Graphical Overview Of Metaphor Buildingneural connections established through simultaneous activation of distinct brain regions emotions(non-sensorimotor)sensorimotorexperiencesConceptual MetaphorsComplexConceptualMetaphorslinguisticmetaphoricalexpressionsother uses ofMetaphors Conventional Conceptual Blending。

材料科学与工程专业英语匡少平课后翻译答案精编WORD版

材料科学与工程专业英语匡少平课后翻译答案精编W O R D版IBM system office room 【A0816H-A0912AAAHH-GX8Q8-GNTHHJ8】Alloy合金applied force作用力amorphous materials不定形材料artificial materials人工材料biomaterials生物材料biological synthesis生物合成biocompatibility生物相容性brittle failure脆性破坏carbon nanotub e碳纳米管carboxylic acid羟酸critical stress临近应力dielectric constant介电常数clay minera l粘土矿物cross-sectional area横截面积critical shear stress临界剪切应力critical length临界长度curing agent固化剂dynamic or cyclic loading动态循环负载linear coefficient of themal expansio n性膨胀系数electromagnetic radiation电磁辐射electrodeposition电极沉积nonlocalizedelectrons游离电子electron beam lithography电子束光刻elasticity 弹性系数electrostation adsorption静电吸附elastic modulus弹性模量elastic deformation弹性形变elastomer弹性体engineering strain工程应变crystallization 结晶fiber-optic光纤维Ethylene oxide环氧乙烷fabrication process制造过程glass fiber玻璃纤维glass transition temperature 玻璃化转变温度heat capacity热熔Hearing aids助听器integrated circuit集成电路Interdisplinary交叉学科intimate contact密切接触inert substance惰性材料implant移植individual application个体应用deformation局部形变mechanical strength机械强度mechanical attrition机械磨损Mechanical properties力学性Materials processing材料加工质mechanical behavior力学行为magnetic permeability磁导率magnetic hybrid technique混合技术induction磁感应mass per unit of volume单位体积质量monomer identity单体种类molecular mass分子量microsphere encapsulation technique微球胶囊技术macroscopical宏观的naked eye 肉眼nonlocalized nanoengineered materials纳米材料nanostructured materials纳米结构材料nonferrous metal有色金属线nucleic acid核酸nanoscale纳米尺度Nanotechnology纳米技术nanobiotechnology纳米生物技术nanocontact printing纳米接触印刷optical property光学性质optoelectronic device光电设备oxidation degradation 氧化降解piezoelectric ceramics压电陶瓷Relative density相对密度stiffnesses刚度sensor传感材料semiconductors半导体specific gravity比重shear 剪切Surface tention表面张力self-organization自组装static loading静载荷stress area应力面积stress-strain curves应力应变曲线sphere radius球半径submicron technique亚微米技术substrate衬底supramolecalar超分子sol-gel method溶胶凝胶法thermal/electrical conductivity 热/点导率thermoplastic materials热塑性材料Thermosetting plastic热固性塑料thermal motion热运动toughness test韧性试验tension张力torsion扭曲Tensile Properties拉伸性能Two-dimentional nanostructure二维纳米结构Tissue engineering组织工程transplantation of organs器官移植the service life使用寿命the longitudinal direction纵向the initial length of the materials初始长度the acceleration gravity重力加速度the normal vertical axis垂直轴the surface to volume ratio 比表面密度the burgers vector伯格丝矢量the mechanics and dynamics of tissues 组织力学和动力学phase transformation temperature相转变温度plastic deformation塑性形变Pottery陶瓷persistence length余晖长度polymer synthesis聚合物合成Polar monomer记性单体polyelectrolyte高分子电解质pinning point钉扎点plasma etching 等离子腐蚀pharmacological acceptability药理接受性pyrolysis高温分解ultrasonic treatment超射波处理yield strength屈服强度vulcanization硫化1-1:直到最近，科学家才终于了解材料的结构要素与其特性之间的关系。

英文原版薛定谔科普

英文原版薛定谔科普Quantum mechanics, as proposed by Austrian physicist ErwinSchrödinger, is a fundamental theory in physics that describes the behavior of particles at the smallest scales. It provides a mathematical framework for understanding the wave-particle duality of matter and the probabilistic nature of physical interactions. Although quantum mechanics is widely considered to be one of the most successful theories in science, it is also one of the most perplexing and counterintuitive.量子力学是由奥地利物理学家薛定谔提出的一种基本理论，描述了粒子在最小尺度上的行为。

它为理解物质的波粒二象性和物理相互作用的概率性提供了数学框架。

虽然量子力学被广泛认为是科学中最成功的理论之一，但也是最令人困惑和反直觉的。

One of the fundamental principles of quantum mechanics is the superposition principle, which states that a system can exist in multiple states simultaneously until it is measured. This idea challenges our classical understanding of physical reality, where objects are expected to have definite properties at all times. Thefamous thought experiment known as Schrödinger's cat illustrates this concept, where a cat trapped in a box is considered both alive and dead until the box is opened and observed.量子力学的一个基本原理是叠加原理，它表明一个系统可以同时存在多个状态，直到被测量出来。

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Extrinsic-intrinsicconcept&complementarityK.SvozilInstitutfürTheoretischePhysikTechnischeUniversitätWienWiednerHauptstraße8-10/136A-1040Vienna,Austriae1360dab@AWIUNI11.EDVZ.UniVie.AC.AT

1IntroductionEpistemological,theintrinsic/extrinsicconcept,or,byanothernaming[1,2],theendo-physics/exophysicsconcept,isrelatedtothequestionofhowamathematicaloralogi-caloranalgorithmicuniverseisperceivedfromwithin/fromtheoutside.Thephysicaluniverse,bydeﬁnition,canbeperceivedfromwithinonly.Extrinsicorexophysicalperceptioncanbeconceivedasahierarchicalprocess,inwhichthesystemunderobservationandtheexperimenterformatwo-levelhierarchy.Thesystemislaidoutandtheexperimenterpeepsateveryrelevantfeatureofitwithoutchangingit.Therestrictedentanglementbetweenthesystemandtheexperimentercanberepresentedbyaone-wayinformationﬂowfromthesystemtotheexperimenter;thesystemisnotaffectedbytheexperimenter’sactions.(Logiciansmightpreferthetermmetaoverexo.)Intrinsicorendophysicalperceptioncanbeconceivedasanon-hierarchicalef-fort.Theexperimenterispartoftheuniverseunderobservation.Experimentsusedevicesandprocedureswhicharerealisablebyinternalresources,i.e.,fromwithintheuniverse.Thetotalintegrationoftheexperimenterintheobservedsystemcanberepresentedbyatwo-wayinformationﬂow,where“measurementapparatus”and“ob-servedentity”areinterchangeableandanydistinctionbetweenthemismerelyamatterofintentandconvention.Endophysicsislimitedbytheself-referentialcharacterofanymeasurement.Anintrinsicmeasurementcanoftenberelatedtotheparadoxicalattempttoobtainthe“true”valueofanobservablewhile—throughinteraction—itcauses“disturbances”oftheentitytobemeasured,therebychangingitsstate.Amongotherquestionsonemayask,“whatkindofexperimentsareintrinsicallyoperationalandwhattypeoftheorieswillbeintrinsicallyreasonable?”Imagine,forexample,someartiﬁcialintelligencelivingina(hermetic)cyberspace.Thisagentmightdevelopa“naturalscience”byperformingexperimentsanddevelop-ingtheories.Itistemptingtospeculatethatalsoaﬁgureinanovel,imaginedbythepoetandthereader,issuchanagent.Sinceincyberspaceonlysyntacticstructuresarerelevant,onemightwonderifcon-cernsofthisagentaboutits“hardwarebasis,”e.g.,whetheritis“madeof”billardballs,

1electriccircuits,mechanicalrelaysornervecells,aremysticorevenpossible(cf.H.Putnam’sbrain-in-a-tankanalysis[4]).Idontthinkthisisnecessarilyso,inparticulariftheagentcouldinﬂuencesomefeaturesofthishardwarebasis.Oneexampleisahardwaredamagecausedbycertaincomputervirusesby“heatingup”computercom-ponentssuchasstorageorprocessors.Iwouldliketocallthistypeof“back-reaction”ofavirtualrealityonitscomputingagent“virtualbackﬂowinterception”(VBI).In-trinsicphenomenologically,VBIcouldmanifestitselfbysomeviolationofa“supers-electionrule;”i.e.,bysomevirtualphenomenonwhichviolatesthefundamentallawsofavirtualreality,suchassymmetry&conservationprinciples.Noattemptismadehereto(re-)writeacomprehensivehistoryofrelatedcon-cepts;butafewhallmarksarementionedwithoutclaimofcompleteness.Histori-cally,Archimedesconceived“pointsoutsidetheworld,fromwhichonecouldmovetheearth.”Archimedes’useof“pointsoutsidetheworld”wasinamechanicalratherthaninametatheoreticalcontext:heclaimedtobeabletomoveanygivenweightbyanygivenforce,howeversmall.The18’thcenturyphysicistB.J.Boscovichrealisedthatitisnotpossibletomeasuremotionsortransformationsifthewholeworld,includ-ingallmeasurementapparataandobserverstherein,becomesequallyaffectedbythesemotionsortransformations(cf.O.E.Rössler[2],p.143).Fictionwritersinformallyelaboratedconsequencesofintrinsicperception.E.A.Abbot’sFlatlanddescribesthelifeoftwo-andonedimensionalcreaturesandtheirconfrontationwithhigherdimen-sionalphenomena.TheFreiherrvonMünchhausenrescuedhimselffromaswampbydragginghimselfoutbyhisownhair.Amongcontemporaryscienceﬁctionauthors,D.F.Galouye’sSimulacronThreeandSt.Lem’sNonServiamstudysomeaspectsof

artiﬁcialintelligenceinwhatcouldbecalled“cyberspaces.”MediaartistssuchasPeterWeibelcreate“virtualrealities”or“cyberspaces”andareparticularyconcernedabouttheinterfacebetween“reality”and“virtualreality,”bothpracticallyandphilosoph-ically.Finally,byoutperformingtelevision&computergames,commercial“virtualreality”productsmightbecomeverybigbusiness.Fromtheseexamplesitcanbeseenthatconceptsrelatedtointrinsicperceptionmaybecomefruitfulforphysics,thecom-putersciencesandartaswell.Alreadyin1950(19yearsafterthepublicationofGödel’sincompletenessthe-orems),K.Popperhasquestionedthecompletenessofself-referentialperceptionof“mechanic”computingdevices[5].PopperusestechniquessimilartoZeno’sparadox(whichhecalls“paradoxofTristramShandy”)and“Gödeliansentences”toargueforakindof“intrinsicindeterminism.”Inapioneeringstudyonthetheoryof(ﬁnite)automata,E.F.MoorehaspresentedGedanken-experimentsonsequentialmachines[6].There,E.F.Mooreinvestigated