Cohomological non-rigidity of generalized real Bott manifolds of height 2

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[语言学]胡壮麟版《语言学教程》名词解释

[语言学]胡壮麟版《语言学教程》名词解释

胡壮麟《语言学教程》术语表第一章phonology音系学grammar语法学morphology形态学syntax句法学lexicology词汇学general linguistics普通语言学theoretical linguistics理论语言学historical linguistics历史语言学descriptive linguistics描写语言学empirical linguistics经验语言学dialectology方言学anthropology人类学stylistics文体学signifier能指signified所指morphs形素morphotactics语素结构学/形态配列学syntactic categories句法范畴syntactic classes句法类别序列sub-structure低层结构super-structure上层结构open syllable开音节closed syllable闭音节checked syllable成阻音节rank 等级level层次ding-dong theory/nativistic theory本能论sing-song theory唱歌说yo-he-ho theory劳动喊声说pooh-pooh theory感叹说ta-ta theory模仿说animal cry theory/bow-wow theory模声说Prague school布拉格学派Bilateral opposition双边对立Mutilateral opposition多边对立Proportional opposition部分对立Isolated opposition孤立对立Private opposition表缺对立Graded opposition渐次对立Equipollent opposition均等对立Neutralizable opposition可中立对立Constant opposition恒定对立Systemic-functional grammar系统功能语法Meaning potential意义潜势Conversational implicature会话含义Deictics指示词Presupposition预设Speech acts言语行为Discourse analysis话语分析Contetualism语境论Phatic communion寒暄交谈Metalanguage原语言Applied linguistics应用语言学Nominalism唯名学派Psychosomatics身学第二章trachea/windpipe气管tip舌尖blade舌叶/舌面front舌前部center舌中部top舌顶back舌后部dorsum舌背root舌跟pharynx喉/咽腔laryngeals喉音laryngealization喉化音vocal cords声带vocal tract声腔initiator启动部分pulmonic airstream mechanism肺气流机制glottalic airstream mechanism喉气流机制velaric airstream mechanism腭气流机制Adam’s apple喉结Voiceless sound清音Voiceless consonant请辅音Voiced sound浊音Voiced consonant浊辅音Glottal stop喉塞音Breath state呼吸状态Voice state带音状态Whisper state耳语状态Closed state封闭状态Alveolar ride齿龈隆骨Dorsum舌背Ejective呼气音Glottalised stop喉塞音Impossive内爆破音Click/ingressive吸气音Segmental phonology音段音系学Segmental phonemes音段音位Suprasegmental超音段Non-segmental非音段Plurisegmental复音段Synthetic language综合型语言Diacritic mark附加符号Broad transcription宽式标音Narrow transcription窄式标音Orthoepy正音法Orthography正字法Etymology词源Active articulator积极发音器官Movable speech organ能动发音器官Passive articulator消极发音器官Immovable speech organ不能动发音器官Lateral边音Approximant [j,w]无摩擦延续音Resonant共鸣音Central approximant中央无摩擦延续音Lateral approximant边无摩擦延续音Unilateral consonant单边辅音Bilateral consonant双边辅音Non-lateral非边音Trill [r]颤音trilled consonant颤辅音rolled consonant滚辅音Labal-velar唇化软腭音Interdental齿间音Post-dental后齿音Apico-alveolar舌尖齿龈音Dorso-alveolar舌背齿龈音Palato-alveolar后齿龈音Palato-alveolar腭齿龈音Dorso-palatal舌背腭音Pre-palatal前腭音Post-palatal后腭音Velarization软腭音化Voicing浊音化Devoicing清音化Pure vowel纯元音Diphthong二合元音Triphthong三合元音Diphthongization二合元音化Monophthongization单元音化Centring diphthong央二合元音Closing diphthong闭二合元音Narrow diphthong窄二合元音Wide diphthong宽二合元音Phonetic similarity语音相似性Free variant自由变体Free variation自由变异Contiguous assimilation临近同化Juxtapostional assimilation邻接同化Regressive assimilation逆同化Anticipatory assimilation先行同化Progressive assimilation顺同化Reciprocal assimilation互相同化Coalescent assimilation融合同化Partial assimilation部分同化Epenthesis插音Primary stress主重音Secondary stress次重音Weak stress弱重音Stress group重音群Sentence stress句子重音Contrastive stress对比重音Lexical stress词汇重音Word stress词重音Lexical tone词汇声调Nuclear tone核心声调Tonetics声调学Intonation contour语调升降曲线Tone units声调单位Intonology语调学Multilevel phonology多层次音系学Monosyllabic word多音节词Polysyllabic word单音节次Maximal onset principle最大节首辅音原则第三章词汇liaison连音contracted form缩写形式frequency count词频统计a unit of vocabulary词汇单位a lexical item词条a lexeme词位hierarchy层次性lexicogrammar词汇语法morpheme语素nonomorphemic words单语素词polymorphemic words多语素词relative uninterruptibility相对连续性a minimum free form最小自由形式the maximum free form最大自由形式variable words 可变词invariable words不变词paradigm聚合体grammatical words(function words)语法词/功能词lexical words(content words)词汇词/实义词closed-class words封闭类词opened-class words开放类词word class词类particles小品词pro-form代词形式pro-adjective(so)代形容词pro-verb(do/did)代副词pro-adverb(so)代动词pro-locative(there)代处所词/代方位词determiners限定词predeterminers前置限定词central determiners中置限定词post determiners后置限定词ordinal number序数词cardinal number基数词morpheme词素morphology形态学free morpheme自由词素bound morpheme黏着词素root词根affix词缀stem词干root morpheme词根语素prefix前缀infix中缀suffix后缀bound root morpheme黏着词根词素inflectional affix屈折词缀derivational affix派生词缀inflectional morphemes屈折语素derivational morphemes派生语素word-formation构词compound复合词endocentric compound向心复合词exocentric compound离心复合词nominal endocentric compound名词性向心复合词adjective endocentric compound形容词性向心复合词verbal compound动词性复合词synthetic compound综合性复合词derivation派生词morpheme语素phoneme音位morphonology形态语音学morphophomemics形态音位学morphemic structure语素结构phonological structure音素结构monosyllabic单音节polysyllabic多音节phonological conditioned音位的限制morphological conditioned形态的限制coinage/invention新创词语blending混成法abbreviation缩写法acronym首字母缩写法back-formation逆序造次/逆构词法analogical creation类比构词法borrowing借词法loanword借词loanblend混合借词loanshift转移借词loan translation翻译借词loss脱落addition添加metathesis换位assimilation同化contact assimilation接触性同化contiguous assimilation临近性同化theory of least effort省力理论non- contiguous assimilation非临近性同化distant assimilation远距离同化morpho-syntactic change形态-句法变化morphological change形态变化syntactical change句法变化finite element有定成分semantic change语义变化multisemous多种意义broadening词义扩大narrowing词义缩小meaning shift词义转移class shift词性变换folk etymology俗词源orthographic change拼写的变化conversion变换/变码domain范围/领域meaning shift意义转移split infinitives分裂不定式(She was told to regularly classes)calque仿造词语clipping截断法metanalysis再分化finiteness定式proximate(this)近指代词obviative(that)远指代词non-productivity/unproductive非多产性semiotics符号学paradigmatic relations聚合关系associative relations联想关系syntagmatic relations组合关系sequential relations序列关系logogram语标register语域passive vocabulary消极词汇lexis/vocabulary词汇表第四章句法number数gender性case格nominative主格vocative呼格accusative兵格genitive属格dative与格ablative离格tense 时aspect体perfective完成体imperfective未完成体concord/agreement一致关系/协同关系government支配关系the governor支配者the governed被支配者signified能指signifier所指syntagmatic relationship组合关系paradigmatic relationship聚合关系associative relationship联想关系animate noun有生名词the two axes两根坐标坐标轴immediate constituent analysis(ICanalysis for short)直接成分分析法linear structure线性结构hierarchical structure层级结构construction结构体constituent成分substituability替换性labeled tree diagram标签树形图endocentric/headed construction向心结构/中心结构exocentric construction离心结构subordinate construction主从结构coordinate construction并列结构recapitulation再现the declarative陈述句the interrogative疑问句dative movement与格移位morph-phonemic rule形态音位规则constituent morphemes成分规则affix hopping词缀越位nominalization名物化object-deletion宾语删除subject-deletion主语删除categories语类lexicon词库temporal subject表时间的主语syntactic limitation句法限制standard theory标准理论trace theory语迹理论the same index带同标志government管辖binding约束a rule system规则系统a principle system原则系统constituent command(C-command forshort)成分统制plain English普通英语anaphor照应语pronominal指代语r-expression(referential-expression)指称语INFL(inflection)形态变化reciprocals(each other)相互代词accessible subject可及主语local domain局部语域binding domain约束语域logophoricity主人公视角CS(computational system)计算系统Merger合并move移动theme主位rheme述位empty subject空主语objective order客观顺序subjective order主观顺序actual sentence division实义句子切分法functional sentence perspective 功能句子观communicative dynamism (CD)交际动力bipartition二分法tripartite classification三分法representative function表达功能expressive function表情功能appellative/vocative function称呼功能conative function意欲功能poetic function诗学功能ideational function概念功能interpersonal function人际功能textual function语篇功能transitivity及物性actor动作者mood system语气系统the finite verbal operator限定部分residue剩余部分indicative直陈语气imperative祈使语气mental-process(a process of sensing)心理过程(感觉过程)relational process(a process of being)关系过程(属性过程)verbal process(a process of saying)言语过程(讲话过程)existential process生存过程第四章句法number数gender性case格nominative主格vocative呼格accusative兵格genitive属格dative与格ablative离格tense 时aspect体perfective完成体imperfective未完成体concord/agreement一致关系/协同关系government支配关系the governor支配者the governed被支配者signified能指signifier所指syntagmatic relationship组合关系paradigmatic relationship聚合关系associative relationship联想关系animate noun有生名词the two axes两根坐标坐标轴immediate constituent analysis(ICanalysis for short)直接成分分析法linear structure线性结构hierarchical structure层级结构construction结构体constituent成分substituability替换性labeled tree diagram标签树形图endocentric/headed construction向心结构/中心结构exocentric construction离心结构subordinate construction主从结构coordinate construction并列结构recapitulation再现the declarative陈述句the interrogative疑问句dative movement与格移位morph-phonemic rule形态音位规则constituent morphemes成分规则affix hopping词缀越位nominalization名物化object-deletion宾语删除subject-deletion主语删除categories语类lexicon词库temporal subject表时间的主语syntactic limitation句法限制standard theory标准理论trace theory语迹理论the same index带同标志government管辖binding约束a rule system规则系统a principle system原则系统constituent command(C-command for short)成分统制plain English普通英语anaphor照应语pronominal指代语r-expression(referential-expression)指称语INFL(inflection)形态变化reciprocals(each other)相互代词accessible subject可及主语local domain局部语域binding domain约束语域logophoricity主人公视角CS(computational system)计算系统=derivational procedure推导系统Merger合并move移动theme主位rheme述位empty subject空主语objective order客观顺序subjective order主观顺序actual sentence division实义句子切分法functional sentence perspective 功能句子观communicative dynamism (CD)交际动力bipartition二分法tripartite classification三分法representative function表达功能expressive function表情功能appellative/vocative function称呼功能conative function意欲功能poetic function诗学功能ideational function概念功能interpersonal function人际功能textual function语篇功能transitivity及物性actor动作者mood system语气系统the finite verbal operator限定部分residue剩余部分indicative直陈语气imperative祈使语气mental-process(a process of sensing)心理过程(感觉过程)relational process(a process of being)关系过程(属性过程)verbal process(a process of saying)言语过程(讲话过程)existential process生存过程empiricism经验主义(洛克,白板说)rationalism 理性主义(笛卡尔)mentalism心灵主义new empiricism新经验主义(Bloomfield)priori先天综合判断(康德Kant)Cartesian linguistics笛卡尔语言学派Syntactic structure (SS)早期转换句法时期Standard theory (ST)标准理论时期Extended Standard theory (EST)扩展的标准理论Revised Standard theory(REST)扩展的休正标准理论The theory of government and binding(GB theory)管辖和约束理论时期(管约论)Minimalist program (MP)最简方案时期Structural description结构描写式Performance system应用系统Modular theory模块理论Spell-out拼写Language faculty语言机制/官能Mental organ心智器官Knowledge of language 语言知识Meaning potential 意义潜势Context culture 文化语境Field语场Tenor语旨Mode语式pivot words轴心词mental construct心理构念theoretical cognitive psychology理论认知心理学psychological faculty心理官能autosyn/autogram/autoknow语法自主(arbitrariness任意性,systemacity系统性, self-containedness自足性)typological functionalism类型学功能主义extreme functionalism极端的功能主义external functionalism外部功能主义integrative functionalism一体化功能注主义exceptional case marking例外格标记specifier标定成分fall-category maximal projection全语类的最大投射two-segment category两节语类complement domain补足语区域minimal domain最小区域internal domain内部区域checking domain检验区域sisterhood姐妹关系minimizing chain link最小语链联结representational system表达系统strict cyclic principle严格的层级条件structure-preserving principle结构保存原则C-commanding condition成分统领条件articulatory-perceptual system发音-听音系统conceptual-intentional system概念-意旨系统interface conditions中介条件full-interpretation完全解释原则procrastination逻辑形式操作优先原则greed句法操作自利原则the shortest linkage principle最短联接原则the shortest movement principle最短移位原则primarycomplement/modifier(referential NP)一级补语位/修饰语位(定指名词短语)secondary complement(non- referentialNP) 二级补语位(非定指名词短语)empty category principle空范畴原则aspect checking特征验证aspect feature基本体貌特征ASPP is functional projection .ASPP是功能投射.crossing branch交叉分支across the board extraction抽取跨界移动principles-and-parameters framework原则与参数语法head parameter中心语参数logical form(LF)逻辑形式phonetic form(PF)语音形式spell-out拼读phonological component音韵部分overt component显性部分covert component隐性部分core computation核心运算asymmetric c-command不对称成分统制linear correspondence axiom线形对应定理adjunction加接determiner限定词concatenate联结linearization线性化functional parameterization hypothesis功能参数设定假设right-branching右向分支X’(V,N,A,P)词项X’’=XP=Xmax是X的二阶投射结构Y’’=指示语specifierZ’’=补述语complementIP=屈折短语inflection phraseXP=general phrase structureC HL人类语言的运算系统=computational system for humanlanguageLCA线性对应定理=linearcorrespondence axiomXmin=X0=最小投射。

群落内物种多样性发生与维持的一个假说

群落内物种多样性发生与维持的一个假说

生物多样性 1997,5(3):161~167CHIN ESE BIODIV ERSIT Y群落内物种多样性发生与维持的一个假说3张大勇 姜新华(兰州大学生物系干旱农业生态国家重点实验室, 兰州 730000)摘 要 本文根据作者对竞争排除法则的研究而提出了一个新的群落多样性假说。

按照作者的观点,占用相同生态位的物种可以稳定共存;这样,群落内物种多样性将受到4个基本因子所控制。

它们分别是:(Ⅰ)生态位的数量;(Ⅱ)区域物种库的大小;(Ⅲ)物种迁入速率,以及(Ⅳ)物种灭绝速率。

该假说强调区域生物地理过程与局域生态过程共同决定了群落内种多样性的大小及分布模式。

关键词 局域物种多样性,物种分化,区域物种库,生态位,竞争排除法则A hypothesis for the origin and maintenance of within2community species diversity/Zhang Dayong,JiangXinhu a//CHINESE BIODIVERSIT Y.—1997,5(3):161~167This paper formulates a novel hypothesis of community diversity on the basis of rejecting the competitive exclu2 sion principle.Since we accept the view that many species could occupy the same niche,local s pecies diversity is considered to be controlled by four fundamental factors,which are,res pectively,(Ⅰ)the number of niches in the community,(Ⅱ)the size of regional species2pool,(Ⅲ)species immigration rate,and(Ⅳ)species extinc2 tion rate.The hypothesis suggests that both regional biogeographic processes and local ecological processes will play an important role in determining the magnitude and pattern of community diversity.K ey w ords local species diversity,speciation,regional species2pool,niche,competitive exclusion principle Author’s address Department of Biology&State K ey Laboratory of Arid Agroecology,Lanzhou Univer2sity,Lanzhou 7300001 引言由于环境污染和生境破坏等人类活动的影响,大规模物种灭绝已成为当今社会所密切关注的一个焦点。

Generalization of human fear acquisition and extinction within a novel arbitrary stimulus category.

Generalization of human fear acquisition and extinction within a novel arbitrary stimulus category.

Generalization of Human Fear Acquisition and Extinction within a Novel Arbitrary Stimulus CategoryEllen Vervoort*,Bram Vervliet,Marc Bennett,Frank BaeyensCentre for the Psychology of Learning and Experimental Psychopathology,Faculty of Psychology and Educational Sciences,University of Leuven,Leuven,BelgiumAbstractAdaptive anxiety relies on a balance between the generalization of fear acquisition and fear extinction.Research on fear (extinction)generalization has focused mostly on perceptual similarity,thereby ignoring the importance of conceptual stimulus relations in humans.The present study used a laboratory procedure to create de novo conceptual categories of arbitrary stimuli and investigated fear and extinction generalization among these stimuli.A matching-to-sample task produced two four-member categories of abstract figures.Next,a member from one category was coupled with an aversive electrical stimulation,while a member from the other category was presented alone.As expected,conditioned fear responses generalized to the other members of the first category(skin conductance and online shock-expectancy).Subsequent extinction of the conditioned member also generalized to the other members.However,extinguishing a non-conditioned member failed to reduce fear of the conditioned member itself.We conclude that fears generalize readily across conceptually related stimuli,but that the degree of extinction generalization depends on the stimulus subjected to extinction.Citation:Vervoort E,Vervliet B,Bennett M,Baeyens F(2014)Generalization of Human Fear Acquisition and Extinction within a Novel Arbitrary Stimulus Category.PLoS ONE9(5):e96569.doi:10.1371/journal.pone.0096569Editor:Simon Dymond,Swansea University,United KingdomReceived January28,2014;Accepted April8,2014;Published May5,2014Copyright:ß2014Vervoort et al.This is an open-access article distributed under the terms of the Creative Commons Attribution License,which permits unrestricted use,distribution,and reproduction in any medium,provided the original author and source are credited.Funding:This research was supported by a PhD scholarship of the KU Leuven Research Fund,and by a KU Leuven Centre for Excellence grant PF/10/005.The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.Competing Interests:The authors have declared that no competing interests exist.*E-mail:ellen.vervoort@ppw.kuleuven.beIntroductionTraumatic experiences can result in fearful reactions to a wide range of trauma-related stimuli,even if they are themselves innocuous[1].This is modeled in the Pavlovian fear conditioning procedure where pairings of a neutral stimulus(conditioned stimulus,CS)and an aversive stimulus(unconditioned stimulus, US)result in the subsequent expression of fear towards the CS. The CS and US have arguably become associated in memory, thereby establishing the CS as a predictive signal of the aversive US and eliciting fear of that specific CS.In many cases,however, traumatic experiences will yield fears of stimuli far beyond the actual traumatic situation[2].This generalization of fear can greatly increase the impact of a traumatic event and pose a great burden on daily life[3,4].It may also complicate psychothera-peutic interventions.Extinction-based psychotherapies involve repeated exposures to fear-arousing situations until the fear declines[5].This technique is highly efficacious but the question is to what extent it remedies the entire range of generalized fear-eliciting situations and events.Previous research has shown that while conditioned fears generalize easily over perceptually related stimuli,extinction of fear does not[6,7].The present study focuses on conceptual relations between stimuli as a source of fear generalization and investigates the general impact of extinction with a target stimulus.Generalization occurs when a conditioned(fear)response is elicited by a stimulus different from the actual CS[8].For instance,stimuli that bear physical similarity with the CS will typically evoke a certain degree of conditioned responding(e.g., [3,6–7,9]).As well as this perceptual-based interaction,humans have a tendency to approach stimuli in a conceptual way. Dunsmoor,White,and LaBar[10]found that conceptual similarities between stimuli(e.g.,spider and web)enhanced the generalization of conditioned fear.That is,learned fear general-ized more easily between these stimuli compared with unrelated stimuli.The ability to link stimuli according to conceptual knowledge plays an important role in the acquisition and generalization of new learning and it constitutes a significant extension of the generalization research field.However,the use of naturalistic concepts and categories has the disadvantage of diminished experimental control over their learning histories [10].Often,members of one category will have been experienced together(e.g.,spider-web),leaving the possibility open that the generalization follows directly experienced associations rather than abstract category membership.We decided to investigate fear generalization with de novo created stimulus categories,in order to maximize experimental control.This excludes any influence of previous pairings of these stimuli.We also controlled for perceptual overlap between stimuli,by selecting entirely arbitrary stimuli.In addition,the current study broadened the focus to include generalization of fear extinction.This allows for the balance between acquisition and extinction generalization among members of stimulus categories to be studied.For the above purposes,we combined the standard Pavlovian fear conditioning procedure with a version of the matching-to-sample(MTS)task(e.g.,[11,12]).This is an operant conditioning procedure through which a number of arbitrary‘comparison’stimuli are directly related to one central‘sample’stimulus.Following this training,stimulus relations that had never been explicitly trainedcan emerge spontaneously.These derived relations entail a reversal of the trained relation such that samples are related to comparisons(known as symmetry)and a combination of the trained relations such that comparisons become related to one other (known as equivalence)[11].As these stimuli become functionally substitutable a new category is said to be formed[13].Previous research on stimulus equivalence has demonstrated that new behaviors trained to one member of a category will generalize to the other members without ever having been experienced together and without any perceptual overlap(e.g.,[14–20]).An earlier study by Dougher,Augustson,Markham,Greenway, and Wulfert[16]demonstrated generalization of both conditioned fear and extinction among members of the same de novo created category.However,the conclusions were based on a very small number of participants(N=8)and only at face value(no statistical tests).This contrasts with contemporary research on perceptual generalization of fear(extinction)that uses larger numbers of participants and adequate statistical testing methods.Valverde, Luciano,and Barnes-Holmes[21]have replicated the generaliza-tion of acquisition effect found by Dougher et al.,using conditioning parameters and statistical analyses consistent with contemporary research standards.However,given the potential importance of this phenomenon in the development of clinical anxiety,more experimental evidence is desirable.In addition, Dougher et al.investigated generalization of extinction after conditioning all members of one and the same category. Extinction generalization is typically investigated by extinguishing only one generalization stimulus followed by tests of the original CS and other generalization stimuli[6,7,22–24].For instance, Roche,Kanter,Brown,Dymond,and Fogarty[25]extinguished either the original CS or one generalization stimulus and then examined the generalization of extinction to related members. However,significant procedural differences between this study and the study by Dougher et al.make it difficult to deduce unambiguous conclusions about extinction generalization.The current research method constitutes a combination of these two studies and can therefore shed light on this matter.The current study used the procedure of Dougher et al.([16], Experiment1)to investigate category-based generalization of fear and extinction with contemporary standards derived from perceptual generalization research.An electrical stimulus served as aversive US.Fear reactions were measured implicitly through skin conductance responses and explicitly through trial-by-trial shock expectancy ratings.We hypothesized that stimuli concep-tually related to a stimulus paired with the US(referred to as CS+) would elicit higher skin conductance responses and US expectancy ratings than stimuli related to a stimulus that is never followed by the US(referred to as CS-).It was further assessed to what extent extinction generalizes to the other stimuli of a category.More specifically,extinction with the original CS+was compared to extinction with a generalization stimulus.Methods and MaterialsThe study consisted of two phases(See Figure1).In the first phase two four-member stimulus categories were established using a MTS procedure.The second phase involved a classical conditioning procedure.It consisted of an acquisition phase and an extinction phase,involving stimuli from both categories.Both after acquisition and after extinction,all stimuli were presented once,to test for generalization of the conditioned responses through implicit stimulus relations derived during the MTS task.Ethics statementThis study was approved by the local ethics committee of the University of Leuven(Faculty of Psychology and Educational Sciences).All participants signed a written informed consent.The minimum age to participate was set at18.ParticipantsFifty-one psychology students(39females)participated in the experiment.They could choose to be reimbursed with course credits or8euro/hour.Sixteen of these participants were excluded during the experiment as they did not meet the pre-established criteria in the first phases(see below).The35participants(27females)who did succeed were randomly assigned to two experimental groups:GS-ext group(N=18,mean age=19.611,SD=2.19)and CS-ext group(N=17,mean age=19.941,SD=3.523).ApparatusThe stimuli used in this experiment were12abstract geometrical figures(See Figure2).Eight of these stimuli were divided into two arbitrary categories each containing four figures. The selection of these eight stimuli and the composition of the categories were randomized.All stimuli will be represented alphanumerically based on the category(category1=CAT+ =A1,B1,C1,D1,category2=CAT-=A2,B2,C2,D2and four remaining stimuli=A3,B3,C3,D3).All stimuli,464cm,were black on a white background and were presented on a computer screen.The screen was located at eye-level and the distance from the participant was approximately50cm.Presentation of the stimuli was controlled by Affect3software[26].A2ms electro-cutaneous stimulus served as unconditioned stimulus(US).It was delivered by a Digitimer DS7A constant current stimulator (Hertfordshire,UK)via a pair of11-mm Fukuda Standard Ag/ AgCl electrodes to the wrist of the left hand.The electrodes were filled with K-Y jelly.The intensity of the shock was determined by the participant as‘‘uncomfortable,but not painful’’(M intensity =1.63mA;SD=.99).A skin conductance coupler from Coulbourn Instruments(model V71-23,Allentown,PA)was used to record electrodermal activity during the experiment.While measuring this skin conductance,the coupler applied a constant voltage of0.5V across a pair of sintered-pellet silver chloride electrodes(8mm),with a distance of approximately7mm between them.These were attached to the palm of the left hand, which was first cleaned with tap water.These electrodes were also filled with K–Y jelly.The resulting conductance signal was submitted through a Labmaster DMA12-bit analog-to-digital converter(Scientific Solutions,Solon,Ohio)and digitized at 10HZ from2s prior to CS onset until8s after CS offset. Participants used their right hand to operate the computer mouse in order to indicate expectancy ratings.This was done via an11-point scale which appeared on the bottom of the computer screen; 0(unlikely)to10(very likely).ProcedureAfter completion of the informed consent participants were led to the experimental room.Electrodes were then fitted and a work-up procedure was used to select a shock intensity that was ‘‘definitely uncomfortable but not painful’’.Next,participants were informed that no shocks would occur in the first task of the experiment,and that when this task was done,new instructions would appear which would warn them of the possibility of electrical stimulation.After this information,the experiment itself began with on-screen Dutch instructions:‘‘When the experiment begins,you will see sets of four symbols on the screen;one at the top and three at the bottom –one on the left,one in the middle,and one on the right.Your task is to choose the correct symbol at the bottom of the screen by pressing the numeric keys 1,2or 3.During the first part of this phase you will get feedback on every ter you will not get feedback every time.However,there is always a correct answer.During the first part of this phase the task will be easy and it is tempting not to pay attention.However,the experiment will increase in difficulty,and choosing the correct symbols in the latter part of this phase will depend on the knowledge you gain during the early parts ofthe experiment.Things that you learn in this part of the study may be important later on.’’Category training and testing phase (matching-to-sample task).The first phase was divided into three parts (see Figure 1).The aim of this phase was to create two four-member stimulus equivalence categories.All trials in this phase began with a sample stimulus appearing on the top of the screen.After 2s,3comparison stimuli appeared in a row on the bottom of the screen whose position from left to right was randomized.Participants could choose a comparison stimulus by pressing the corresponding numeric key;key 1for the stimulus on the left,key 2fortheFigure 1.A schematic overview of the experimental phases.The upper panel represents the trials used in the matching-to-sample training,symmetry test and equivalence test,in order to create two novel stimulus categories (A1-B1-C1-D1and A2-B2-C2-D2).The first stimulus always represents the sample stimulus,the other three stimuli are the comparison stimuli.The correct comparison stimulus is indicated in bold.The lower panel represents the fear conditioning phase (acquisition,generalization of acquisition test,extinction,generalization of extinction test).The ‘‘+’’sign indicates that this stimulus is followed by an electric shock in 8out of 10trials.The ‘‘2’’sign indicates that this stimulus is never followed by a shock during those trials.doi:10.1371/journal.pone.0096569.g001stimulus in the middle and key 3for the stimulus on the right.A key press removed all stimuli and the screen turned black.During training trials feedback would then occur (‘‘Correct’’or ‘‘Wrong’’)for 5s followed by a 2second inter-trial interval (ITI).During testing trials no feedback would follow a response.The MTS task started with a training phase which taught participants six stimulus relations (A1-B1,A1-C1,A1-D1,A2-B2,A2-C2,A2-D2).These trials were introduced in blocks,each containing 6different trial types in random order:A1-B1/B2/B3,A1-C1/C2/C3,A1-D1/D2/D3,A2-B1/B2/B3,A2-C1/C2/C3,A2-D1/D2/D3.Note that the stimuli in bold are the correct comparison stimuli in presence of the accompanying sample stimulus.Stimuli B3,C3and D3were only used as third,incorrect,comparisons to reduce the likelihood that participants could learn the correct responses by exclusion.Stimulus A3had the same function in the next parts of the MTS phase.These stimuli played no further role in the fear conditioning part of the experiment.To pass the initial training phase,46trials had to be correct in a consecutive series of 48trials.If this was the case,then the participant moved on to the second part of the category phase that consisted of symmetry test trials.Here,A1,A2and A3served as comparison stimuli,while B1,C1,D1,B2,C2and D2now served as sample stimuli.The relations tested for in this phase were B1-A1,C1-A1,D1-A1,B2-A2,C2-A2,D2-A2.There were six trials in a single block presented randomly :B1-A1/A2/A3,C1-A1/A2/A3,D1-A1/A2/A3,B2-A1/A2/A3,C2-A1/A2/A3,D2-A1/A2/A3.As aforementioned,feedback was no longer given following testing trials.Participants had to achieve 16correct trials out of 18to move on to the next test phase.This part consisted of blocks of 18trial types.These included the 6symmetry trial types from the previous phase and 12new equivalence trial types.Equivalence trials tested for the emergence of relations between the B-,C-and D-stimuli:B1-C1/C2/C3,B1-D1/D2/D3,C1-B1/B2/B3,C1-D1/D2/D3,D1-B1/B2/B3,D1-C1/C2/C3,B2-C1/C2/C3,B2-D1/D2/D3,C2-B1/B2/B3,C2-D1/D2/D3,D2-B1/B2/B3,D2-C1/C2/C3.The next phase began once in at least 34out of 36trials correct responses were made.The criteria used in the category training and testing phases were based upon pilot work,in which all participants meeting these criteria appeared to be able to reconstruct the categories afterwards.All participants in this pilot study who succeeded on this task,managed to do this within 30minutes.Therefore,participants had a time limit of 30minutes in the experiment itself to complete this phase.If they ran out of time,orin other words,if they did not meet the criteria during training or test,they were excluded from the rest of the experiment.Acquisition and extinction phase.New instructions initi-ated the acquisition phase:‘‘The first phase of the experiment has been successfully completed!Now we are moving on to the second phase.From time to time,you will see a figure on the screen.Some figures will sometimes be followed by an electric shock,other figures will not.It is your task to report whether you expect a shock after these stimuli or not,by indicating a certain spot on a scale from 0to 100,which will appear on the bottom of the screen.You can use your free hand to do this.For every figure,you have a couple of seconds to give an answer.’’During this phase,stimuli B1and B2were each presented 10times in random order.Each stimulus was presented for 8s followed by an ITI randomized between 10and 15s.Eight out of 10B1presentations were immediately followed by a shock (US)while 2out of 10were not.B1was therefore aversively conditioned to predict US.One of the two B1conditioning trials without a shock always took place in the first half of this phase,while the other one occurred in the second half.This 80%contingency between B1and shock was applied to attenuate extinction learning during the subsequent generalization test.B2was never followed by the shock.During the presentation of a stimulus,the expectancy scale appeared on the bottom of the screen.In this 8second period,the participants had to indicate the likelihood of a US onset on a scale between 0and 100.The left extreme on the scale (number 0)was labeled ‘‘Certainly no shock’’while the right extreme (number 100),was labeled ‘‘Certainly a shock’’.The intermediate point of the scale (number 50)was labeled ‘‘Uncertain’’.Participants could click on a certain spot on the scale to indicate a value.After doing this,a dot would appear on that spot,which could still be replaced if the participant changed his or her mind.Each time a new trial began the dot was removed and had to be placed on the scale again.This trial pattern,the stimulus durations and the inter trial interval were the same throughout the rest of the experiment.Stimuli from CAT +(A1,B1,C1and D1)and CAT-(A2,B2,C2and D2)were then presented once each in the absence of a US in order to test for generalization of conditioned fear.They appeared quasi-randomly onscreen for 8s followed by a 10–15s ITI.Participants were first exposed to the B and C stimuli.These were presented in two possible patterns:B2-B1-C2-C1or C2-C1-B2-B1.A stimulus from CAT-was always presented first,to reduce the effects of extinction during generalization testing.After presenting these 4stimuli,the other stimuli (A1,A2,D1and D2)were presented in random order.One group was subsequently presented with B1and B2in extinction (CS-ext Group).A second group was presented with two related stimuli,C1and C2,also in extinction (GS-ext group).Each stimulus was presented 15times and all trials were randomized.The US never followed a stimulus.Finally,a second generalization test took place.Again,all stimuli from both categories were presented once,without being followed by a shock.The sequence of these trials was determined by the same rules as in the test phase after acquisition.Immediately after the experiment,a manipulation check took place to verify whether the participants could reconstruct the two stimulus categories they had learned during the MTS task.Participants were handed 12flash cards with the abstract figures (A1,B1,C1,A2,B2,C3,A3,B3,C4)printed on each.Their task was to divide them on a table into their constituent categories.NoFigure 2.Abstract figures used in the experiment to create novel categories.doi:10.1371/journal.pone.0096569.g002further information was given about the number or the size of the groups.Data analysisThe US expectancy ratings were registered at the moment the stimulus and expectancy scale disappeared from the screen.For the skin conductance response,amplitudes were measured as the peak value in every trial within the0–7.5s interval after CS onset relative to a baseline averaged over the2s prior to CS onset. Negative values were converted into zero and were also included in the analyses.These amplitudes were then range corrected using the largest response elicited by the US,in the9–14s interval after CS onset as the maximum range for each participant.Every amplitude was divided by this maximum US response.Prior to statistical analysis,the obtained values were normalized,using a square root transformation.The alpha-level was set at.05for all analyses.Where Mauchly’s test revealed that sphericity could not be assumed the Greenhouse-Geisser correction is reported.When two or more significant comparisons are described,only the values of the least significant comparison will be reported.Analogical to this,when two or more non-significant comparisons are described, only the values of the comparison that approached significance the most are reported.ResultsAll the participants who succeeded in the MTS training and testing,also did so in the manipulation check at the end of the experiment.The skin conductance responses of two participants were excluded from the analysis because of technical difficulties. Category training and testing phase(matching-to-sample task)No differences were found between the conditions in the mean number of matching-to-sample training and test trials,t(34),1.00, p..32,as was expected(CS-ext group:mean number of training trials=96,SD=30.00;symmetry test trials=27,SD=26.38; equivalence test trials=45,SD=21.93;GS-ext group:mean number of training trials=93,SD=32.03;symmetry test trials= 20,SD=9.90;equivalence test trials=52,SD=35.41). Acquisition phaseUS expectancy ratings.The left panel of Figure3suggests that a differential US expectancy to B1(CS+)and B2(CS2) emerged over the acquisition phase.This was confirmed by a mixed ANOVA,where the one between-subjects variable was condition(CS-ext group and GS-ext group)and two within-subjects variables included stimulus(B1and B2)and trial number (1to10).This analysis revealed a main effect of Stimulus,F(1,17) =1042.34,p,.001,partial n2=.98,and a significant interaction between Stimulus and Trial,F(3.17,53.96)=15.85,p,.001, partial n2=.48.At the last acquisition trial,there was a significant difference between the two stimuli,F(1,17)=109.18,p,.001, partial n2=.87.There were no differences between the two conditions(no Stimulus*Condition*Trial interaction,F(3.17, 53.96)=1.08,p=.37,partial n2=.05).Skin conductance response.Figure4represents the skin conductance responding during acquisition.The same ANOVA as the one carried out in the US expectancy data,showed no significant interaction between Stimulus and Trial,F(6.61,125.56) =1.81,p=.10.However,at the last acquisition trial,there was a significant difference between the two stimuli(F(1,17)=13.99, p=.002,partial n2=.45).Again,no main effect or interaction effect involving Condition was found,F,.42,p..52.Generalization of acquisition testUS expectancy ratings.The right panel of Figure3shows the expectancy ratings of the first test phase.This graph suggests that CAT+elicited higher shock expectancies than CAT2.This was analyzed by conducting a mixed ANOVA with Category(2 levels:CAT+and CAT2)and Stimulus(4levels:A,B,C and D) as within-subjects variables and Condition(CS-ext group and GS-ext group)as a between-subjects variable.This analysis revealed a main effect of Category,F(1,27)=77.92,p,.001,partial n2=.74, and an interaction between Stimulus and Category,F(3, 81)=38.55,p,.001,partial n2=.59.There was no effect of stimulus,F(3,81)=.10,p=.96,partial n2=.004.This indicates that shock expectancies were strongly dependent on the stimulus categories created during the MTS procedure.The main effect of condition was not significant,F(1,27)=.06,p=.81,partial n2=.002,nor was any of its interactions,F,1.22,p..31.Planned comparisons revealed a significant difference between the mean C1and D1ratings versus the mean ratings of C2and D2,F(1, 27)=15.07,p,.001,partial n2=.38.The mean C1rating was not different from D1ratings and C2did not differ from D2ratings,F (1,27),.13,p..72.This suggests that after acquisition of B1(CS+) and B2(CS2),shock expectancy towards C1and D1was elevated while lower towards C2and D2.Stimuli A1and A2were also analyzed,as their relations with the B stimuli had been explicitly trained,in contrast with the relations between the B,C and D stimuli.Interestingly,in both categories the level of shock expectancies elicited by the A stimuli did not differ from the expectancies elicited by the C and D stimuli,F(1,27),1.31, p..26.It is noticeable in this test phase that generalization was not complete.The difference between the conditioned stimuli(B1and B2)appeared to be larger than the difference between the mean ratings for CAT+(A1,C1and D1)and CAT2(A2,C2and D2), F(1,27)=82.61,p,.001,partial n2=.75.Skin conductance response.Figure4suggests similar outcomes as in the shock expectancy data.This was investigated using an ANOVA with Category(2levels:CAT+and CAT2)and Stimulus(4levels:A,B,C and D)as within-subjects variables and Condition(CS-ext group and GS-ext group)as a between-subjects variable.This analysis revealed a main effect of Category,F(1, 29)=7.70,p=.01,partial n2=.21,and no interaction between Category and Stimulus,F(3,87)=.93,p=.43,partial n2=.03.A planned comparison between C1and D1from CAT+on the one hand,and C2and D2from CAT2on the other hand approached significance,F(1,29)=3.73,p=.06,partial n2=.11.Also,there was no difference between C1and D1skin conductance,nor between C2and D2skin conductance,F,.90,p..18.Unexpect-edly,there was no difference in skin conductance response between A1and A2,F(1,29)=.03,p=.87,partial n2,.001. Extinction phaseUS expectancy ratings.Figure5shows the expectancy ratings during the extinction phase,for both conditions.B1seems to elicit more US expectancy than B2during the first trial in CS-ext group,while there is a rather small initial difference in the same direction between C1and C2in GS-ext group.Furthermore, in both conditions these differences seem to extinguish during this phase.This was confirmed by an ANOVA with one between-subjects variable(Condition,2levels:CS-ext group and GS-ext group)and two within-subjects variables(Stimulus:B1/C1and B2/C2,and Trial:1to15).This analysis revealed a significant interaction between Stimulus,Trial and Condition,F(3.15, 91.42)=5.89,p,.001,partial n2=.31.This suggests that the difference between the stimulus from CAT+(B1or C1)and the。

侵袭性牙周炎龈沟液中有机酸与牙龈卟啉单胞菌和齿垢密螺旋体的关系_路瑞芳

侵袭性牙周炎龈沟液中有机酸与牙龈卟啉单胞菌和齿垢密螺旋体的关系_路瑞芳

·论著·侵袭性牙周炎龈沟液中有机酸与牙龈卟啉单胞菌和齿垢密螺旋体的关系路瑞芳1,冯琳2,高学军2,孟焕新1△,冯向辉1(北京大学口腔医学院·口腔医院1.牙周科,2.牙体牙髓科,北京100081)[摘要]目的:分析侵袭性牙周炎(aggressive periodontitis ,AgP )患者龈沟液中牙龈卟啉单胞菌和齿垢密螺旋体对有机酸浓度的影响,初步探讨有机酸在AgP 疾病中的作用。

方法:共20例AgP 患者和14例健康对照者纳入本研究,每位研究对象每象限选一个位点采集龈沟液,分离上清液采用高效毛细管电泳仪检测琥珀酸、乙酸、丙酸、丁酸和异戊酸,分离沉淀物采用PCR 技术检测牙龈卟啉单胞菌和齿垢密螺旋体,并分析其电泳条带的灰度值作为该微生物的PCR 产物量。

结果:AgP 组龈沟液中琥珀酸、乙酸、丙酸、丁酸和异戊酸的浓度,牙龈卟啉单胞菌、齿垢密螺旋体的检出率和PCR 产物量均显著高于健康对照组,其中在牙龈卟啉单胞菌检出组中丁酸浓度显著高于未检出组[2.87(0.99,4.36)mmol /L vs.0.33(0.00,1.44)mmol /L ,P <0.05],琥珀酸、乙酸、丙酸、丁酸和异戊酸浓度均与牙龈卟啉单胞菌产物量呈正相关(r 值分别为0.334,0.548,0.411,0.493,0.273,P <0.05)。

齿垢密螺旋体检出组中有机酸浓度均高于未检出组,琥珀酸1.67(1.15,2.11)mmol /L vs.0.80(0.48,1.06)mmol /L ,乙酸31.95(23.77,43.13)mmol /L vs.12.51(7.57,15.69)mmol /L ,丙酸11.86(6.55,14.98)mmol /L vs.2.82(1.71,7.03)mmol /L ,丁酸3.45(2.41,4.78)mmol /L vs.0.54(0.00,1.56)mmol /L ,异戊酸2.23(1.05,3.85)mmol /L vs.0.62(0.00,2.33)mmol /L ,琥珀酸、乙酸、丙酸和丁酸与齿垢密螺旋体产物量呈显著正相关(r 值为0.443,0.702,0.625,0.557,P <0.05)。

合并危险因素的高钾血症诊治进展

合并危险因素的高钾血症诊治进展

·4587·[32]SHIROBE M,WATANABE Y,TANAKA T,et al. Effect ofan oral frailty measures program on community-dwelling elderly people:a cluster-randomized controlled trial[J]. Gerontology,2021:1-10. DOI:10.1159/000516968.[33]MATSUO K,KITO N,OGAWA K,et al. Improvement oforal hypofunction by a comprehensive oral and physical exercise programme including textured lunch gatherings[J]. J Oral Rehabil,2021,48(4):411-421. DOI:10.1111/joor.13122.[34]NOMURA Y,ISHII Y,SUZUKI S,et al. Nutritional status andoral frailty :a community based study [J]. Nutrients,2020,12(9):E2886. DOI:10.3390/nu12092886.[35]DIBELLO V,LOZUPONE M,MANFREDINI D,et al. Oralfrailty and neurodegeneration in Alzheimer 's disease[J]. Neural Regen Res,2021,16(11):2149-2153. DOI:10.4103/1673-5374.310672.[36]HIRONAKA S,KUGIMIYA Y,WATANABE Y,et al. Associationbetween oral,social,and physical frailty in community-dwelling older adults[J]. Arch Gerontol Geriatr,2020,89:104105. DOI:10.1016/j.archger.2020.104105.[37]BABA H,WATANABE Y,MIURA K,et al. Oral frailty andcarriage of oral Candida in community-dwelling older adults(Check-up to discover Health with Energy for senior Residents in Iwamizawa ;CHEER Iwamizawa)[J]. Gerodontology,2022,39(1):49-58. DOI:10.1111/ger.12621.[38]HIHARA T,GOTO T,ICHIKAWA T. Investigating eatingbehaviors and symptoms of oral frailty using questionnaires[J]. D e n t J (B a s e l ),2019,7(3):E 66. D O I :10.3390/dj7030066.[39]NISHIMOTO M,TANAKA T,TAKAHASHI K,et al. Oral frailtyis associated with food satisfaction in community-dwelling older adults[J]. Nihon Ronen Igakkai Zasshi,2020,57(3):273-281. DOI:10.3143/geriatrics.57.273.[40]HATANAKA Y,FURUYA J,SATO Y,et al. Associationsbetween oral hypofunction tests,age,and sex[J]. Int J Environ Res Public Health,2021,18(19):10256. DOI:10.3390/ijerph181910256.[41]OHARA Y,MOTOKAWA K,WATANABE Y,et al. Associationof eating alone with oral frailty among community-dwelling older adults in Japan[J]. Arch Gerontol Geriatr,2020,87:104014. DOI:10.1016/j.archger.2020.104014.(收稿日期:2022-03-10;修回日期:2022-05-06)(本文编辑:康艳辉)·新进展·合并危险因素的高钾血症诊治进展罗培艺,马良,苟慎菊*【摘要】 高钾血症是临床上的常见问题,其发生的危险因素包括患有肾脏疾病、心血管疾病、糖尿病以及服用影响血钾的药物等。

世界卫生组织关于脑膜炎球菌疫苗的立场文件 2011 年11 …

世界卫生组织关于脑膜炎球菌疫苗的立场文件 2011 年11 …

世界卫生组织关于脑膜炎球菌疫苗的立场文件(2011年11月)依据为各成员国提供卫生政策方面指导意见这一职责,世界卫生组织(WHO)就预防具有全球公共卫生影响的疾病的疫苗及联合疫苗问题,发布一系列定期更新的立场文件。

这些文件着重关注疫苗在大规模免疫规划中的使用,归纳了各相关疾病与疫苗的基本背景信息,并就如何在全世界范围内使用这些疫苗表明了世卫组织目前的立场。

这些文件经外部专家和世卫组织工作人员审阅,并由世卫组织的免疫战略咨询专家组(SAGE)(http://www.who.int/immunization/sage/en/)审核和认可。

这些立场文件主要供各国的公共卫生官员和免疫规划管理人员使用。

对这些立场文件感兴趣的还可能包括一些国际资助机构、疫苗制造厂家、医学界、科学媒体和公众。

本文件反映了脑膜炎球菌疫苗领域的最新进展,为各国在国家免疫接种计划中引进和使用脑膜炎球菌疫苗提供了指导意见。

本文件用于取代2002年10月《疫情周报》公布的关于脑膜炎球菌疫苗的立场文件。

SAGE在2011年4月召开会议,讨论了关于脑膜炎球菌疫苗使用的建议。

该会议提出的证据可参见:http://www.who.int/immunization/sage/previous/en/index.html。

本文件的脚注仅提供了部分核心参考文献。

参考文献清单可从以下网址获取:http://www.who.int/immunization/documents/positionpapers/en/index.html。

通过上述链接及本文的参考文献也可获取分级表,利用这些分级表可以评估支持重要建议的科学证据的质量。

引言流行病学在大多数国家,脑膜炎奈瑟菌(Neisseria meningitidis,脑膜炎双球菌)都已被确认为导致脑膜炎和爆发性败血症的首要原因,并且已构成严重的公共卫生问题。

然而,许多国家(尤其是亚洲国家)的监测数据不完整或缺乏,当前尚无关于本病的全球负担估计。

晚发型cblC型甲基丙二酸尿症合并同型半胱氨酸血症1例报告并文献复习

晚发型cblC型甲基丙二酸尿症合并同型半胱氨酸血症1例报告并文献复习

晚发型cblC型甲基丙二酸尿症合并同型半胱氨酸血症1例报告并文献复习魏景景1,司倩倩2,倪俊2,魏妍平2,钱敏2摘要:目的 探讨晚发型甲基丙二酸尿症合并同型半胱氨酸血症的临床及基因变异特点。

方法 回顾性分析1例MMACHC基因突变致晚发型cblC型甲基丙二酸尿症合并同型半胱氨酸血症患者的临床资料及基因检测结果,并结合文献讨论。

结果 本例男性患者,以双足麻木起病,逐渐出现双下肢僵硬无力,发病前有非特异性精神行为异常症状,此次就诊经基因检测发现MMACHC基因4号外显子存在c.482G>A(p.Arg161Gln)错义突变,与文献报道c.482G>A复合杂合突变不同,本例患者突变类型为纯合突变。

结论 甲基丙二酸尿症合并同型半胱氨酸血症的临床异质性较大,容易漏诊误诊,当出现不明原因的精神行为异常时应考虑该诊断,基因检测是诊断的重要依据,同时也可指导该病的分型。

关键词:甲基丙二酸尿症;同型半胱氨酸血症;晚发型;MMACHC基因;cblC型中图分类号:R596 文献标识码:ALate‑onset cblC‑type methylmalonic aciduria with homocysteinemia:A case report and literature review WEI Jingjing,SI Qianqian, NI Jun, et al.(Department of Neurology, The People's Hospital of Jiaozuo, Jiaozuo 454002, China)Abstract:Objective To investigate the clinical characteristics and gene mutations of late-onset methylmalonic ac‑iduria with homocysteinemia.Methods We retrospectively analyzed the clinical data and genetic test result of one pa‑tient with late-onset cblC-type methylmalonic aciduria with homocysteinemia arising from MMACHC gene mutation. Relevantliterature was reviewed.Results This male patient initially presented with numbness in both feet, and gradually developed stiffness and weakness in both lower limbs, with nonspecific mental and behavioral symptoms before onset. Gene testing de‑tected a missense mutation, c.482G>A(p.Arg161Gln) in exon 4 of the MMACHC gene. It was a homozygous mutation, which was different from compound heterozygous mutations of c.482G>A reported in previous literature.Conclusion Methylmalonic aciduria with homocysteinemia is clinically heterogeneous, with a high possibility of a missed diagnosis or misdiagnosis. The diagnosis should be considered in the presence of mental and behavioral abnormities of unknown cause. Gene detec‑tion is an important basis for the diagnosis and typing of the disease.Key words:Methylmalonic aciduria;Homocysteinemia;Late‑onset;MMACHC gene;cblC typecblC型甲基丙二酸尿症(methylmalonic acid‑uria,MMA)合并同型半胱氨酸血症是一种常染色体隐性遗传代谢性疾病,与MMACHC基因突变继而引起钴胺素代谢障碍相关[1]。

非等位基因

非等位基因

非等位基因概述非等位基因是指同一基因座上的不同等位基因。

等位基因是指在某个给定的基因座上,可以存在多种不同的变体。

每个个体继承了一对等位基因,一对等位基因可能会导致不同的表型表达。

非等位基因的存在使得遗传学研究更加复杂,因为不同的等位基因会对个体的表型产生不同的影响。

背景在生物学中,基因座是指染色体上一个特定的位置,该位置上的基因决定了某个特征的表达方式。

每个基因座上可以有多种不同的等位基因。

等位基因是指在某个特定基因座上的不同基因变体。

每个个体都会继承一对等位基因,通过这对等位基因的不同组合,决定了个体的表型。

然而,并非所有基因座上的等位基因都具有相同的表现型。

非等位基因的影响非等位基因的存在导致不同等位基因会对个体表型产生不同的影响。

有些非等位基因会表现出显性效应,也就是说,当个体继承了一个突变的等位基因时,即使同时继承了一个正常的等位基因,但显性效应会使得突变的等位基因的表型表达得到体现。

相反,有些非等位基因会表现出隐性效应,当个体继承了两个突变的等位基因时,才会表现出突变的表型。

除了显性和隐性效应之外,非等位基因还可能发生两种其他类型的表型效应。

一种是共显效应,当个体继承了两个不同的突变等位基因时,在表型表达上会表现出一种新的特征,这个特征并不是单个突变等位基因所能导致的。

另一种是部分显性效应,当个体继承了两个不同的突变等位基因时,表型表达将介于两个单独突变等位基因的表型之间。

重组和非等位基因重组是指两个不同的染色体交换部分基因序列的过程。

在重组的过程中,非等位基因可能会发生改变,导致新的等位基因组合形成。

这一过程使得非等位基因的表型效应更加复杂,因为新的等位基因可能将不同基因座的效应组合起来。

非等位基因的重要性非等位基因对生物的适应性和多样性起着重要作用。

通过对等位基因的各种组合的研究,人们可以更好地理解基因与表型之间的关系,并揭示遗传变异对物种适应环境的重要性。

总结非等位基因是指同一基因座上的不同等位基因。

突变理论

突变理论
这种由渐变、量变发展为突变、质变的过程,就是突变现象,微积分是不能描述的。以前科学家在研究这类 突变现象时遇到了各式各样的困难,其中主要困难就是缺乏恰当的数学工具来提供描述它们的数学模型。那么, 有没有可能建立一种关于突变现象的一般性数学理论来描述各种飞跃和不连续过程呢?这迫使数学家进一步研究 描述突变理论的飞跃过程,研究不连续性现象的数学理论。1972年法国数学家勒内·托姆在《结构稳定性和形态 发生学》一书中,明确地阐明了突变理论,宣告了突变理论的诞生。
改良型技术创新虽然能很快会被市场上的主流消费者所接受,但随着技术创新的不断改进,改良型创新可能 会导致产品的性能过剩。就变革而言,渐进式的改进其实有一个根本的前提,那就是企业的发展方向是正确的, 对大格局的研判是准确的。否则,南辕北辙,拾遗补缺式的改良只会导致在错误的道路上渐行渐远,改良的后果 只是在原本已经盘根错节积弊深沉的系统中加剧复杂,使问题的解决变得更加困难。
许多年来,自然界许多事物的连续的、渐变的、平滑的运动变化过程,都可以用微积分的方法给以圆满解决。 例如,地球绕着太阳旋转,有规律地周而复始地连续不断进行,使人能极其精确地预测未来的运动状态,这就需 要运用经典的微积分来描述。但是,自然界和社会现象中,还有许多突变和飞跃的过程,飞越造成的不连续性把 系统的行为空间变成不可微的,微积分就无法解决。例如,水突然沸腾,冰突然融化,火山爆发,某地突然地震, 房屋突然倒塌,病人突然死亡……。
多年以来,如何看待世界,存在两种截然对立的观点,达尔文主要从 “渐变”或“连续性”的角度考察世 界,认为自然界的演变是十分缓慢的,这种“渐变论”是当时学术界的主导思想。然而,19世纪末,以达尔文进 化论为基础的连续变异进化观,既无法解释古生物学中大量存在的“化石断层”现象,亦无从说明变异的遗传本 质,正是在这一背景下,荷兰植物学家雨果·德弗里斯 (Hugo De Vries,1848-1935)建立了以“物种的突发产 生”为主要内容的进化学说突变论。

Cell-free nucleic acids as biomarkers in cancer patients

Cell-free nucleic acids as biomarkers  in cancer patients

In 1948, Mandel and Métais 1 described the presence of cell-free nucleic acid (cfNA) in human blood for the first time. This attracted little attention in the scientific com-munity and it was not until 1994 that the importance of cfNA was recognized as a result of the detection of mutated RAS gene fragments in the blood of cancer patients 2,3 (TIMELINE). In 1996, microsatellite altera-tions on cell-free DNA (cfDNA) were shown in cancer patients 4, and during the past decade increasing atten-tion has been paid to cfNAs (such as DNA, mRNA and microRNAs (miRNAs)) that are present at high concentra-tions in the blood of cancer patients (FIG. 1). Indeed, their potential value as blood biomarkers was highlighted in a recent editorial in the journal Science 5.Detecting cfNA in plasma or serum could serve as a ‘liquid biopsy’, which would be useful for numer-ous diagnostic applications and would avoid the need for tumour tissue biopsies. Use of such a liquid biopsy delivers the possibility of taking repeated blood sam-ples, consequently allowing the changes in cfNA to be traced during the natural course of the disease or during cancer treatment. However, the levels of cfNA might also reflect physiological and pathological processes that are not tumour-specific 6. cfNA yields are higher in patients with malignant lesions than in patients without tumours, but increased levels have also been quantified in patients with benign lesions, inflammatory diseases and tissue trauma 7. The physi-ological events that lead to the increase of cfNA during cancer development and progression are still not well understood. However, analyses of circulating DNA allow the detection of tumour-related genetic and epi-genetic alterations that are relevant to cancer develop-ment and progression. In addition, circulating miRNAs have recently been shown to be potential cancer biomarkers in blood.This Review focuses on the clinical utility of cfNA, including genetic and epigenetic alterations that can be detected in cfDNA, as well as the quantification of nucleo s omes and miRNAs, and discusses the relationship between cfNA and micrometastatic cells.Biology of cfNAThe release of nucleic acids into the blood is thought to be related to the apoptosis and necrosis of cancer cells in the tumour microenvironment. Secretion has also been suggested as a potential source of cfDNA (FIG. 1). Necrotic and apoptotic cells are usually phagocytosed by macrophages or other scavenger cells 8. Macrophages that engulf necrotic cells can release digested DNA into the tissue environment. In vitro cell culture experiments indicated that macrophages can be either activated or dying during the process of DNA release 8. Fragments of cellular nucleic acids can also be actively released 9,10. It has been estimated that for a patient with a tumour that weighs 100 g, which corresponds to 3 × 1010 tumour cells, up to 3.3% of tumour DNA may enter the blood every day 11. On average, the size of this DNA varies between small fragments of 70 to 200 base pairs and large fragments of approximately 21 kilobases 12. Tumour cells that circulate in the blood, and micro-metastatic deposits that are present at distant sites, such as the bone marrow and liver, can also contribute to the release of cfNA 13,14.T umours usually represent a mixture of different cancer cell clones (which account for the genomic and epig-enomic heterogeneity of tumours) and other normal cell types, such as haematopoietic and stromal cells. Thus, during tumour progression and turnover both tumour-derived and wild-type (normal) cfNA can be released into the blood. As such, the proportion of cfNA that originates from tumour cells varies owing to the state*Institute of T umour Biology, Center of ExperimentalMedicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.‡Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.Correspondence to K.P . e-mail:pantel@uke.uni-hamburg.de doi:10.1038/nrc3066Published online 12 May 2011microRNAsSmall non-coding RNAmolecules that modulate the activity of specific mRNA molecules by binding and inhibiting their translation into polypeptides.Cell-free nucleic acids as biomarkers in cancer patientsHeidi Schwarzenbach*, Dave S. B. Hoon ‡ and Klaus Pantel*Abstract | DNA, mRNA and microRNA are released and circulate in the blood of cancerpatients. Changes in the levels of circulating nucleic acids have been associated with tumour burden and malignant progression. In the past decade a wealth of information indicating the potential use of circulating nucleic acids for cancer screening, prognosis and monitoring of the efficacy of anticancer therapies has emerged. In this Review, we discuss these findings with a specific focus on the clinical utility of cell-free nucleic acids as blood biomarkers.and size of the tumour. The amount of cfNA is also influ-enced by clearance, degradation and other physiological filtering events of the blood and lymphatic circulation. Nucleic acids are cleared from the blood by the liver and kidney and they have a variable half-life in the circulation ranging from 15 minutes to several hours7. Assuming an exponential decay model and plotting the natural loga-rithm of cfDNA concentration against time, serial DNA measure m ents have shown that some forms of cfNA might survive longer than others. When purified DNA was injected into the blood of mice, double-stranded DNA remained in the circulation longer than single-stranded DNA15. Moreover, viral DNA as a closed ring may survive longer than linear DNA15. However, regardless of its size or configuration, cfDNA is cleared from the circulation rapidly and efficiently16. miRNAs seem to be highly stable, but their clearance rate from the blood has not yet been well studied in cancer patients owing to the novelty of this area of research. The nuclease activ-ity in blood may be one of the important factors for the turnover of cfNA. However, this area of cfNA physiology remains unclear and needs further examination. Circulating cfDNADNA content. In patients with tumours of different histo-pathological types, increased levels of total cfDNA, which consists of epigenomic and genomic, as well as mito-chondrial and viral DNA, have been assessed by different fluorescence-based methods (such as, PicoGreen stain-ing and ultraviolet (UV) spectrometry) or quantitative PCR (such as, SYBR Green and TaqMan). Although cancer patients have higher cfDNA levels than healthy control donors, the concentrations of overall cfDNA vary considerably in plasma or serum samples in both groups17–19. A range of between 0 and >1,000 ng per ml of blood, with an average of 180 ng per ml cfDNA, has been measured20–23. By comparison, healthy subjects have concentrations between 0 and 100 ng per ml cfDNA of blood, with an average of 30 ng per ml cfDNA7. However, it is difficult to draw conclusions from these studies, as the size of the investigated patient cohort is often small and the techniques used to quantify cfDNA vary. A large prospective study assessed the value of plasma DNA levels as indicators for the development of neoplastic or pulmonary disease. The concentration of plasma DNA varied considerably between the European Prospective Investigation into Cancer and Nutrition (EPIC) centres that were involved in the study. This variation was pro-posed to be due to the type of population recruited and/or the treatment of the samples24. However, the quantifica-tion of cfDNA concentrations alone does not seem to be useful in a diagnostic setting owing to the overlapping DNA concentrations that are found in healthy individuals with those in patients with benign and malignant disease. The assessment of cfDNA concentration might prove to be useful in combination with other blood tumour bio-markers. Following surgery, the levels of cfDNA in cancer patients with localized disease can decrease to levels that are observed in healthy individuals25. However, when the cfDNA level remains high, it might indicate the presence of residual tumour cells17. Further studies are needed for the repeat assessment of quantitative cfNA in large cohorts of patients with well-defined clinical parameters. Such investigations will be crucial if we are to use cfDNA as a prognostic biomarker, as will the isolation and processingof cfNA to defined standards (discussed below).cfDNA is composed of both genomic DNA (gDNA) and mitochondrial DNA (mtDNA). Interestingly, the levels of cell-free mtDNA and gDNA do not correlate in some tumour types26,27, indicating the different nature of circulating mtDNA and gDNA. In contrast to two copies of gDNA, a single cell contains up to several hundred copies of mtDNA. Whereas gDNA usually circulates in a cell-free form, circulating mtDNA in plasma exists in both particle-associated and non-particle-associated forms28. Diverging results have been reported regarding whether cell-free mtDNA levels are increased and clinically relevant in cancer patients.The cfDNA can also include both coding and non-coding gDNA that can be used to examine microsatellite instability, loss of heterozygosity (LOH), mutations, poly-morphisms, methylation and integrity (size). In recent years, considerable attention has been paid to non-coding DNA, particularly repetitive sequences, such as ALU (which is a short interspersed nucleic element (SINE)) and as long interspersed nucleotide elements such as LINE1 (REFS 29–31) (discussed below). ALU and LINE1 are dis-tributed throughout the genome and are known to be less methylated in cancer cells compared with normal cells32. Tumour-specific LOH. Genetic alterations found in cfDNA frequently include LOH that is detected using PCR-based assays13,18,33–38(TABLE 1). Although similar plasma- and serum-based LOH detection methods have been used, a great variability in the detection of LOH in cfDNA has been reported. Despite the concordance between tumour-related LOH that is present in cfDNA in blood and LOH that is found in DNA isolated from matched primary tumours, discrepancies have also been found7. These contradictory LOH data that have been derived from blood and tumour tissue and the low incidence of LOH in cfDNA have partly been explained by technical problems and the dilution of tumour-associated cfDNA in blood by DNA released from normal cells11,39–41. Moreover, the abnormal proliferation of benign cells, owing to inflammation or tissue repair processes, for example, leads to an increase in apoptotic cell death, the accumulation of small, fragmented DNA in blood and the masking of LOH42.Alternative approaches, such as the detection of tumour-specific deletions are needed to better address the inherent problems of LOH analyses.Tumour-specific gene mutations.The analysis of cfDNA for specific gene mutations, such as those in KRAS and TP53, is desirable because these genes have a high mutation frequency in many tumour types and contribute to tumour progression43. Additionally, clini-cally relevant mutations in BRAF, epidermal growth factor receptor (EGFR) and adenomatous polyposis coli (APC) have now been studied in cfDNA. Several thera-peutic agents in clinical trials target the KRAS, BRAF, EGFR or p53 pathways44,45, and require the identifica-tion of the mutation status of the patient’s tumour to predict response to treatment. In this regard, cfDNA provides a unique opportunity to repeatedly monitor patients during treatment. In particular, in stage IV cancer patients, biopsies are not possible or repeat sam-pling of primary tumour and metastatic samples is not practical or ethical.The major problem with this approach has been assay specificity and sensitivity. Assays targeting cfDNA mutations require that the mutation in the tumour occurs frequently at a specific genomic site.A major drawback of cfDNA assays is the low frequency of some of the mutations that occur in tumours. In general, wild-type sequences often interfere with cfDNA muta-tion assays. This is due to the low level of cfDNA mutations and the dilution effect of DNA fragments and wild-type DNA in circulation. In PCR-based assays technological design can significantly limit the assay sensitivity and specificity. An example is the KRAS muta-tion tissue assay that can frequently detect mutations in tumour tissues, such as the pancreas, colon and lung;Quantitative real-time clamp PCR assayA technique that uses a peptide nucleic acid clamp and locked nucleic acid probes, which are DNA synthetic analogues that hybridize to complementary DNA and are highly sensitive and specific for recognizing single base pair mismatches.however, cfDNA mutation assays using blood sam-ples have not yet been concordantly successful46–48.New approaches are needed, such as cfDNA sequenc-ing. The BRAF mutation V600E, which is present in>70% of metastatic melanomas, can be detectedin cfDNA and has been shown to be useful in monitor-ing patients with melanoma who are receiving ther-apy49. This mutation has been detected in differentstages of melanoma (according to the American JointCommittee on Cancer (AJCC) Cancer Staging Manual)using a quantitative real-time clamp PCR assay, with thehighest levels found in the more advanced stages49. Thisis one of the first major studies to demonstrate thatcfDNA mutation assays have the sensitivity to monitorpatient responses before and after treatment. The util-ity of a cfDNA BRAF mutation assay has gained moreimportance, as new anti-BRAF drugs, such as PLX4032(Roche)50 and GSK2118436 (GlaxoSmithKline)51, haveshown substantial responses in patients in early clinicaltrials. EGFR mutations that occur in a specific subset ofpatients with lung cancers52–54 make these tumours sen-sitive to EGFR-targeted therapies; however, the detec-tion of EGFR mutations in cfDNA has not been welldeveloped owing to issues with sensitivity and specifi-city. Patients whose tumours have a specific gene muta-tion would be strong candidates for monitoring of theircfDNA in blood for the respective specific mutation.However, sensitivity, specificity and validation needto be carried out in multicentre settings to determinetrue clinical utility. Alternatively, cfDNA assays mightbe more appropriate when used with other biomarkerassays, and this might be applicable to personalizedmedicine, rather than diagnostic screens that can beused across a wide group of cancer patients.DNA integrity. Another assay that is applicable to cfDNAthat has gained interest in recent years is the integrityof non-coding gDNA, such as the repeat sequences ofALU and LINE1. The ALU and LINE1 sequences havebeen referred to as ‘junk DNA’; however, in recentyears evidence has indicated their importance invarious physiological events, such as DNA repair,transcription, epigenetics and transposon-based activ-ity55,56. Approximately 17–18% of the human genomeconsists of LINE1. In normal cells LINE1 sequencesare heavily methylated, restricting the activities ofthese retrotransposon elements and thus preventinggenomic instability. LINE1 sequences are moderatelyCpG-rich, and most methylated CpGs are locatedin the 5′ region of the sequence that can function asan internal promoter23. These forms of DNA can bedetected as cfDNA of different sizes, but also as methyl-ated and unmethylated DNA. Studies on these types ofcfDNA are still in their infancy; however, recent studieshave shown potential prognostic and diagnostic util-ity23,29–31. The assays are based on the observation thatcommon DNA repeat sequences are preferentiallyreleased by tumour cells that are undergoing non-apoptotic or necrotic cell death, and these fragmentscan be between 200 bp and 400 bp in size. The ALU andLINE1 sequences are well interspersed throughout thegenome on all chromosomes, so although specificity understood; tumour burden and tumour cell proliferation rate may have a substantial role in these events. Individual tumour types can release more than one form of cfDNA.for an individual cancer type is lost in these assays, sen-sitivity is enhanced. Using a PCR assay, the integrity of cfDNA ALU sequences in blood has been shown to be sensitive for the assessment of the early stages of breast cancer progression, including micro m etastasis30. DNA integrity cfDNA assays have also been used in testicular, prostate, nasopharyngeal and ovarian cancer31,57–59. These assays are still in their infancy and address an important challenge of whether a ‘universal’ blood biomarker for multiple cancers can be of clinical utility. Further validation of these assays will also determine their clinical utility in specific cancers.Table 1 |Detection of cfDNA and its alterations in patients with different tumour types*cancers in both males and females182. This table is not meant to be comprehensive and is based on our own view of studies that offer substantial clinical insight. cfDNA, cell-free DNA.Epigenetic alterations. Epigenetic alterations can have a substantial effect on tumorigenesis and progression (BOX 1). Several studies have revealed the presence of methylated DNA in the serum or plasma of patients with various types of malignancy (TABLE 1). The detection of methylated cfDNA represents one of the most promising approaches for risk assessment in cancer patients. Assays for the detection of promoter hypermethylation may have a higher sensitivity than microsatellite analyses, and can have advantages over mutation analyses. In gen-eral, aberrant DNA methylation, which seems to be com-mon in cancer, occurs at specific CpG dinucleotides60. The acquired hypermethylation of a specific gene can be detected by sodium bisulphite treatment of DNA, which converts unmethylated (but not methylated) cytosines to uracil. The modified DNA is analysed using either methylation-specific PCR, with primers that are specific for methylated and unmethylated DNA, or DNA sequenc-ing61. Nevertheless, to improve the assay conditions and the clinical relevance, the selection of appropriate tumour-related genes from a long list of candidate genes that are known to be methylated in neoplasia is essential. Although epigenetic alterations are not unique for a single tumour entity, there are particular tumour suppressor genes that are frequently methylated and downregulated in certain tumours62,63. For example, important epigenetic events in carcinogenesis include the hypermethylation of the promoter region of the genes pi-class glutathione S-transferase P1 (GSTP1) and APC, which are the most common somatic genome abnormalities in prostate and colorectal cancer, respectively62,63. Other important methylated genes that have shown prognostic utility using cfDNA assays in significant numbers of patients include RAS association domain family 1A (RASSF1A), retinoic acid receptor-b (RARB), septin 9 (SEPT9), oestrogen receptor-a (ESR1)and cyclin-dependent kinase inhibitor 2A (CDKN2A) (TABLE 1). The first commercial real-time PCR plasma test for the detection of early colorectal cancer (developed by Epigenomics AG and Abbott Molecular) is for the detection of SEPT9. This biomarker is still under-going validation, but it demonstrates the potential diag-nostic screening utility of methylated tumour-related cfDNA to differentiate cancer patients from healthy individuals and to identify the tumour type.It is also possible to detect tumour-related alterations in histone modifications in the blood. By monitoring changes in the circulating histones and DNA methylation pattern, the antitumour effects of histone deacetylase and histone methyltransferase inhibitors may be evalu-ated and consequently allow a better screening of cancer patients64,65.Circulating nucleosomes.Circulating gDNA that is derived from tumours seems to predominantly exist as mononucleosomes and oligonucleosomes, or it is bound to the surface of blood cells by proteins that harbour specific nucleic acid-binding properties66. A nucleosome consists of a histone octamer core wrapped twice by a 200 bp-long DNA strand. Under physiological condi-tions these complexes are packed in apoptotic particles and engulfed by macrophages67. However, an excess of apoptotic cell death, as occurs in large and rapidly pro-liferating tumours or after chemotherapy treatment, can lead to a saturation of apoptotic cell engulfment and thus increased nucleosome levels in the blood68. The detection of circulating nucleosomes that are associ-ated with cfDNA suggests that DNA in blood retains at least some features of the nuclear chromatin during the process of release.Enzyme-linked immunosorbent assays (ELISAs) have been developed to quantify circulating nucleosomes. As increased concentrations are found in both benign and malignant tumours, high nucleosome levels in blood are not indicators of malignant disease69. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the increased serum levels of nucleosomes have been linked to breast cancer progression70. As typical cell-death products, the quan-tification of circulating nucleosomes seems to be valu-able for monitoring the efficacy of cytotoxic cancer therapies71. For example, platinum-based chemotherapy induces caspase-dependent apoptosis of tumour cells and an increase in circulating nucleosomes in the blood of patients with ovarian cancer17. Moreover, the outcome of therapy can be indicated by nucleosome levels during the first week of chemotherapy and radiotherapy in patients with lung, pancreatic and colorectal cancer, as well as in patients with haematological malignancies71.Viral DNA. Viral cfDNA can also be detected in some tumour types. Viruses, such as human papillomavirus (HPV), hepatitis B virus (HBV) and Epstein–Barr virus (EBV), are aetiological factors in various malignancies, such as nasopharyngeal, cervical, head and neck, and hepatocellular cancer and lymphoma72–75. Their specific DNA may have the potential to be used as molecular biomarkers for neoplastic disease. Associations between circulating viral DNA and disease have been reported for EBV with Hodgkin’s disease, Burkitt’s lymphoma and nasopharyngeal carcinoma; for HBV with some forms of hepatic cell carcinoma; and for HPV with head and neck, cervical and hepatocellular cancers (TABLE 1). The clinical utility of EBV cfDNA in diagnosis and prognosis of nasopharyngeal carcinoma has been demonstrated in multiple studies with large cohorts of patients76–80, and the use of this cfDNA has became one of the leading cfDNA blood tests for the assessment of nasopharyngeal carci-noma progression in Hong Kong, Taiwan and China, where this cancer is highly prevalent77,78,81. The limitationof most viral cfNA assays is that benign viral infections that are caused by the same viruses can complicate the interpretation of results, particularly in diagnostic screen-ing. Establishing clinically meaningful cut-off levels is important to move these screens into the clinic. Genometastasis.The genometastasis hypothesis describes the horizontal transfer of cell-free tumour DNA to other cells that results in transformation. If true, metastases could develop in distant organs as a result of a transfection-like uptake of dominant oncogenes that are released from the primary tumour82. García-Olmo et al.83 showed that plasma isolated from patients with colon cancer is able to transform NIH-3T3 cells and that these cells can form carcinomas when injected into non-obese diabetic-severe combined immunodeficient mice83. Whether this biological function of circulating DNA has relevance in human blood is an aspect to be considered in the future.cfDNA assay issuesOne of the problems in evaluating cfNA is the standard-ization of assays, such as isolation technologies, standards, assay conditions, and specificity and sensitivity7. It remains controversial whether plasma or serum is the optimal sampling specimen. The diversity of protocols and reagents currently in use impedes the comparison of data from different laboratories.The pre-analytical phases of cfDNA analysis such as blood collection, processing (plasma and serum), storage, baseline of patients, diurnal variations and accurate clinical conditions need to be better defined before comparisons and clinical utility can be validated84.A major technical issue that hampers consistency in all the cfDNA assays is the efficacy of the extraction pro-cedures, with only small amounts of DNA obtained from plasma and serum. Another key issue is quanti-fication before assessment on specific assay platforms. Improvement is needed in these aspects for cfDNA analysis to be more robust, consistent, comparative and informative. Extraction of cfDNA can be carried out in accordance with many methods; for example, commer-cial kits, company in-house procedures or individual laboratory protocols. To date no approach has been truly developed that is consistent, robust, reproduc-ible, accurate, and validated on a large-scale patient and normal donor population. If these issues were solved a better universal standardization for the comparison of results would be provided and the clinical utility of the assays could be addressed. The development of a direct DNA assay without extraction would override many of these problems30. As new approaches in the assessment of cfDNA, such as next-generation sequencing, are being developed, the issue of extraction of DNA will continue to complicate cfDNA biomarker assay development and regulatory group approval.The other major issue for cfDNA assessment is that after DNA extraction, different platform assays are used for analysis. This can vary owing to the type of cfDNA being analysed, assay sensitivity and specificity, and ana-lytical approach. These variables are important and need to be standardized for consensus analysis and reporting. The development of PCR-based assay standardization is needed in order to report clinical and prognostic biomarker results that are similar to those outlined in the recent minimal information for the publication of quantitative real-time PCR guidelines85. However, this may take time to reach an international consensus, as has been apparent with the standardization of other cancer blood biomarkers. Unfortunately, the rate of approval of new cancer blood biomarkers over the past decade has been very slow. New regulatory guidelines, such as those listed for tumour biomarkers in clinical practice by the National Academy of Clinical Biochemistry (NACB USA)84, should help to resolve some of these issues. The NACB website provides up-to-date informative detailed guidelines with references of pre-analytical and post- analytical phases, assay validation, internal quality controls, proficiency and requirements for minimiz-ing the risk of method-related errors for biomarkers. Nevertheless, as with other types of biomarkers, new reg-ulatory guidelines mean that developing cfNA biomarkers will be more time-consuming and costly. Circulating cfRNAmRNA content. Besides the quantification of cfDNA, cir-culating gene transcripts are also detectable in the serum and plasma of cancer patients. It is known that RNA released into the circulation is surprisingly stable in spite of the fact that increased amounts of RNases circulate in the blood of cancer patients. This implies that RNA may be protected from degradation by its packaging into exosomes86, such as microparticles, microvesicles or multivesicles, which are shed from cellular surfaces into the bloodstream87. The detection and identification of RNA can be carried out using microarray technologies or reverse transcription quantitative real-time PCR88. Serum thyroglobulin levels are a specific and sensi-tive tumour marker for the detection of persistent or recurrent thyroid cancer. Levels of thyroglobulin change during thyroid hormone-suppressive therapy, as well as after stimulation with thyroid-stimulating hormone, and the levels correlate well with disease progression. The measurement of mRNA levels of thyroid-specific tran-scripts might be useful in the early detection of tumour relapse89. However, another study has shown that the detection of circulating thyroglobulin mRNA one year after thyroidectomy might be of no use in the prediction of early and midterm local and distant recurrences of this disease90.In patients with breast cancer, levels of CCND1 mRNA (encoding cyclin D1) identified patients with poor overall survival in good-prognosis groups and patients who were non-responsive to tamoxifen91. Nasopharyngeal carcinoma has been associated with disturbances in the integrity of cell-free circulating RNA, suggesting that the measurement of plasma RNA integrity may be a useful biomarker for the diagnosis and monitoring of malignant diseases92. Several groups have tried to detect human telo-merase reverse transcriptase (TERT) mRNA in plasma, and have not found any association between the pres-ence of this mRNA and clinicopathological parameters7.。

诺贝尔奖得主Brown和Goldstein

诺贝尔奖得主Brown和Goldstein

Statins uesd as therapy medicine
1975年,一名日本科学家Akira Endo, 发现某些 霉菌会合成强烈的抑制HMG CoA还原酶的产物。 Brown 和Goldstein 证实这些抑制剂可以增加狗 的肝脏的LDL受体的水平,并且诱导血浆LDL水 平的显著降低。随即,这种药物就进入了临床 试验,发现能够显著降低人血浆LDL水平,保护 心脏病的患者减少心血管事件的发生。 这一类药物,统称为他汀,在全世界每天有超 过3千万的人在服用他汀药物。
Dr. Michael Brown
Dr. Joseph Goldstein
在美国西南医学中心的两位科 学家Brown和Goldstein因为在 胆固醇代谢机制研究中的卓越 贡献共同获得了1985年的诺贝 尔医学和生理学奖。基于他们 的发现,一种降脂类药-他汀 类药物在临床上的得以广泛应 用,据估计,单单在美国,目 前就有大约2000万人在服用他 汀类药物(年销售额高达260 亿美元),每年有6000~7000 人因此而延长了生命。
Dissecting Receptor Regulation and Its Implications for Statin Therapy
从最初的对LDL受体的研究中, Brown/Goldstein的团队认 识到这个受体是可以被调控的。当细胞的胆固醇被去除时, 受体的数量增加。相反,当细胞内胆固醇堆积时,受体基 因则表达受抑制受体的数量就下降。 在体内,肝脏产生了大部分的LDL受体因此肝脏从血中清 除了大部分的LDL。 Goldstein和Brown 意识到如果降低肝 细胞内的胆固醇则肝脏表达的LDL受体的数量就会增加。 这就可以通过摄入低胆固醇和饱和脂肪酸的饮食来达到。 也可以通过服用抑制胆固醇合成的药物来实现。也就是抑 制胆固醇合成的限速酶3-羟基-3-甲基戊二酰辅酶A还原酶 (HMG CoA 还原酶)。

医学遗传学词汇Glossary

医学遗传学词汇Glossary

Acceptor splice site??The boundary between the 3’end of an intron and the 5’end of the following exon. Also called 3’splice site.剪接受体位点:内含子3′末端与下一个外显子5′端之间的交界处。

又称3′剪接位点。

Acrocentric??A type of chromosome with the centromere near one end. The human acrocentric chromosomes (13, 14, 15, 21, and 22) have satellited short arms that carry genes for ribosomal RNA.近端着丝粒(染色体):着丝粒位于接近染色体臂端部的染色体。

人类近端着丝粒染色体(第13、14、15、21和22号)短臂的随体携带有编码核糖体RNA的基因。

Adverse selection??A term used in the insurance industry to describe the situation in which individuals with private knowledge of having an increased risk for illness, disability, or death buy disproportionately more coverage than those at a lower risk. As a result, insurance premiums, which are based on averaging risk across the population, are inadequate to cover future claims.逆向选择:保险业的专有名词,指投保人知晓其有较高的患病、残疾或死亡风险,但隐瞒真相购买相关保险。

胡敏文 杨寿康 解释学 对话理论和权力话语观照下的汉英翻译

胡敏文 杨寿康  解释学 对话理论和权力话语观照下的汉英翻译

解释学、对话理论和权力话语观照下的汉)英翻译胡敏文杨寿康X(中南大学铁道校区外国语学院湖南长沙410075)摘要:解释学和对话理论阐明,所有文学翻译的译文必然是杂合的,即纯粹的归化或异化皆不可能。

译文杂合程度受权力话语和跨丈化交际效果的制约。

杂合的汉英译文有利于中国文化在全球化的文化场中获得认同和推广。

以汉英习语翻译为例,异化应视做主要翻译策略;直译加注应视为主要翻译方法。

关键词:解释学对话理论权力话语汉英习语翻译杂合异化Abstract:Philosop hical hermeneutics and dialogical theory expose that all literal translated texts are hybrids,that is,there.s no purely foreignizing or domesticating translated texts.The degree of hybridi ty is conditioned by the power of discourse and the effects of cross-cultural communicati on.Hybrid C-E translated texts may play a positive role in promoting unique Chinese culture in the globa-l izing culture field.T ake C-E translation of set expressions as an ex ample,foreignizaiton is to be applied as the dominan t translation strategy;literal translation plus notes is to be exploited as the primary translation method.Key words:philosophical hermeneutics dialogical theory theory of power and discourse C-E translation of set expressions hybrid hybridi ty foreignization一从20世纪80年代至今,归化、异化之争一直是译界争论的焦点。

春兰炭疽病致病菌Colletotrichum boninense的鉴定及生物学特性分析

春兰炭疽病致病菌Colletotrichum boninense的鉴定及生物学特性分析

园艺学报,2015,42 (10):1993–2001.Acta Horticulturae Sinicadoi:10.16420/j.issn.0513-353x.2015-0084;http://www. ahs. ac. cn 1993春兰炭疽病致病菌Colletotrichum boninense的鉴定及生物学特性分析周平兰1,4,唐新科4,龙岳林2,*,周小毛2,3,*(1湖南农业大学园艺园林学院,长沙 410128;2湖南农业大学植物保护学院,长沙 410128;3湖南省农业科学院农业生物技术研究中心,长沙 410125;4湖南科技大学生命科学学院,湖南湘潭 411201)摘 要:以湖南野生春兰(Cymbidium goeringii)引种驯化过程中发生的炭疽病病株为试验材料,分离、鉴定病原菌,分析营养因子和非营养因子对病原菌生长的影响。

结果表明:春兰炭疽病病原菌为博宁炭疽菌(Colletotrichum boninense Moriwaki,Sato & Tsukiboshi);适合生长的培养基有PDA、PSA和CSA;能有效利用多种碳源,最适合的为葡萄糖,有利生长的有机氮为酵母膏和蛋白胨,无机氮为硝酸钾;光照与黑暗对菌丝生长的影响无显著性差异;适宜pH 5.0 ~ 8.0;在10 ~ 35 ℃均能生长,最适温度为25 ℃;处理20 min,菌丝和孢子的致死温度分别为48和50 ℃。

关键词:春兰;炭疽病;Colletotrichum boninense;生物学特性中图分类号:S 682.31 文献标志码:A 文章编号:0513-353X(2015)10-1993-09 Identification of Pathogen Colletotrichum boninense from Cymbidium goeringii and Its Biological CharacteristicsZHOU Ping-lan1,4,TANG Xin-ke4,LONG Yue-lin2,*,and ZHOU Xiao-mao2,3,*(1College of Horticulture and Landscape,Hunan Agricultural University,Changsha 410128,China;2College of Plant Protection,Hunan Agricultural University,Changsha 410128,China;3Center of Biotechnology Research,Hunan Academy of Agricultural Sciences,Changsha 410125,China;4School of Life Science,Hunan University of Science and Technology,Xiangtan,Hunan 411201,China)Abstract:Pathogen causing anthracnose on Cymbidium goeringii in Hunan was isolated and identified,and the impact of nutritional and non-nutritional factors on its growth was analyzed. The results showed that the pathogen of anthracnose on Cymbidium goeringii was Colletotrichum boninense Moriwaki,Sato & Tsukiboshi. This strain grew well on media of PDA,PSA and CSA. For carbon sources,it grew better in glucose than in sucrose,maltose or fructose. Yeast extract,peptone and KNO3 were the better organic and inorganic nitrogen sources,respectively.The optimal acidity of culture medium was pH 5.0–8.0,light or darkness. Its hyphae could extend at 15–35 ℃,and the optimum temperature was 25 ℃. The lethal temperatures of hyphae and spores were 48 ℃ and 50 ℃ in 20 min,respectively.Key words:Cymbidium goeringii;anthracnose;Colletotrichum boninense;biological characteristic收稿日期:2015–05–15;修回日期:2015–08–04基金项目:湖南省科技厅重点项目(2010NK2007)* 通信作者Author for correspondence(E-mail:27991288@;zhouxm1972@)Zhou Ping-lan,Tang Xin-ke,Long Yue-lin,Zhou Xiao-mao.Identification of pathogen Colletotrichum boninense from Cymbidium goeringii and its biological characteristics. 1994Acta Horticulturae Sinica,2015,42 (10):1993–2001.春兰(Cymbidium goeringii)又称草兰、山兰、朵朵香等,古代称兰,系兰科(Orchidaceae)兰属(Cymbidium)多年生草本植物(卢思聪,1994)。

胡壮麟语言学名词解释总结

胡壮麟语言学名词解释总结

胡壮麟语言学名词解释总结Define the following terms:1. design feature:are features that define our human languages,such as arbitrariness,duality,creativity,displacement,culturaltransmission,etc.2. function: the use of language tocommunicate,to think ,nguage functions inclucle imformative function,interpersonalfunction,performative function,interpersonal function,performative function,emotive function,phatic communion,recreational function and metalingual function.3. etic: a term in contrast with emic which originates from American linguist Pike’s distinction of phonetics and phonemics.Being etic mans making far too many, as well as behaviouslyinconsequential,differentiations,just as was ofter the case with phonetic vx.phonemic analysis in linguistics proper.4. emic: a term in contrast with etic which originates from American linguist Pike’s distinction of phonetics and phonemics.An emic set of speech acts and events must be one that is validated as meaningful via final resource to the native members of a speech communith rather than via qppeal to the investigator’s ingenuith or intuition alone.5. synchronic: a kind of description which takes a fixedinstant(usually,but not necessarily,the present),as its point of observation.Most grammars are of this kind.6. diachronic:study of a language is carried through the course of its history.7. prescriptive: the study of a language is carried through the course of its history.8. prescriptive: a kind of linguistic study in which things are prescribed how ought to be,ying down rules for language use. 9. descriptive: a kind of linguistic study in which things are just described.10. arbitrariness: one design feature of human language,which refers to the face that the forms of linguistic signs bear no natural relationship to their meaning.11. duality: one design feature of human language,which refers to the property of having two levels of are composed of elements of the secondary.level and each of the two levels has its own principles of organization.12. displacement: one design feature of human language,which means human language enable their users to symbolize objects,events and concepts which are not present c in time and space,at the moment of communication.13. phatic communion: one function of human language,which refers to the social interaction of language.14. metalanguage: certain kinds of linguistic signs or terms for the analysis and description of particular studies.15. macrolinguistics: he interacting study between language and language-related disciplines such aspsychology,sociology,ethnograph,science of law and artificial intelligence etc.Branches of macrolinguistics include psycholinguistics,sociolinguistics, an thropological linguistics,et16. competence: language user’s underlying knowledge about the system of rules.17. performance: the actual use of language in concrete situation.18. langue: the linguistic competence of the speaker.19. parole: the actual phenomena or data of linguistics(utterances).20. Articulatory phonetics: the study of production of speechsounds. 21. Coarticulation: a kind of phonetic process in which simultaneous or overlapping articulations are involved..Coarticulation can be further divided into anticipatory coarticulation and perseverative coarticulation.22. Voicing: pronouncing a sound (usually a vowel or a voiced consonant) by vibrating the vocal cords.23. Broad and narrow transcription: the use of a simple set of symbols in transcription is called broad transcription;the use of a simple set of symbols in transcription is called broad transcription;while,the use of more specific symbols to show more phonetic detail is referred to as narrow transcription.24. Consonant: are sound segments produced by constricting or obstructing the vocal tract at some place to divert,impede,or completely shut off the flow of air in the oral cavity.25. Phoneme: the abstract element of sound, identified as being distinctive in a particular language.26. Allophone:any of the different forms of a phoneme(eg.<th>is an allophone of /t/in English.When /t/occurs in words like step,it is unaspirated<t>.Both<th>and <t>are allophones of the phoneme/t/. 27. Vowl:are sound segments produced without such obstruction,so no turbulence of a total stopping of the air can be perceived.28. Manner of articulation; in the production of consonants,manner of articulation refers to the actual relationship between the articulators and thus the way in which the air passes through certain parts of the vocal tract.29. Place of articulation: in the production of consonants,place of articulation refers to where in the vocal tract there isapproximation,narrowing,or the obstruction of air.30. Distinctive features: a term of phonology,i.e.a property which distinguishes one phoneme from another.31. Complementary distribution: the relation between tow speech sounds that never occur in the same environment.Allophones of the same phoneme are usually in complementary distribution.32. IPA: the abbreviation of International Phonetic Alphabet,which is devised by the International Phonetic Association in 1888 then it has undergong a number of revisions.IPA is a comprised system employing symbols of all sources,such as Roman small letters,italics uprighted,obsolete letters,Greek letters,diacritics,etc.33. Suprasegmental:suprasegmental featuresare those aspects of speech that involve more than single sound segments.The principalsupra-segmental features aresyllable,stress,tone,,and intonation. 34. Suprasegmental:aspects of speech that involve more than single sound segments.The principle suprasegmental features aresyllable,stress,tone,and intonation.35. morpheme:the smallest unit of language in terms of relationship between expression and content,a unit that cannot be divided into further small units without destroying or drastically altering themeaning,whether it is lexical or grammatical.36. compound oly morphemic words which consist wholly of free morphemes,such as classroom,blackboard,snowwhite,etc.37. inflection: the manifestation of grammatical relationship through the addition of inflectional affixes,such asnumber,person,finiteness,aspect and case,which do not change the grammatical class of the stems to which they are attached.38. affix: the collective term for the type of formative that can be used only when added to another morpheme(the root or stem).39. derivation: different from compounds,derivation shows the relation between roots and affixes.40. root: the base from of a word that cannot further be analyzed without total lass of identity.41. allomorph:; any of the different form of a morpheme.For example,in English the plural mortheme is but it is pronounced differently in different environments as/s/in cats,as/z/ in dogs and as/iz/ in classes.So/s/,/z/,and /iz/ are all allomorphs of the plural morpheme.42. Stem: any morpheme or combination of morphemes to which an inflectional affix can be added.43. bound morpheme: an element of meaning which is structurally dependent on the world it is added to,e.g. the plural morpheme in “dog’s”.44. free morpheme: an element of meaning which takes the form of anindependent word.45. lexeme:A separate unit of meaning,usually in the form of aword(e.g.”dog in the manger”)46. lexicon: a list of all the words in a language assigned to various lexical categories and provided with semantic interpretation.47. grammatical word: word expressing grammatical meanings,such conjunction,prepositions,articles and pronouns.48. lexical word: word having lexical meanings,that is ,those which refer to substance,action and quality,such as nouns,verbs,adjectives,and verbs.49. open-class: a word whose membership is in principle infinite or unlimited,such as nouns,verbs,adjectives,and many adverbs.50. blending: a relatively complex form of compounding,in which two words are blended by joining the initial part of the first word and the final part of the second word,or by joining the initial parts of the two words.51. loanvoord: a process in which both form and meaning are borrowed with only a slight adaptation,in some cases,to eh phonological system of the new language that they enter.52. loanblend: a process in which part of the form is native and part is borrowed, but the meaning is fully borrowed.53. leanshift: a process in which the meaning is borrowed,but the form is native.54. acronym: is made up form the first letters of the name of an organization,which has a heavily modified headword.55. loss: the disappearance of the very sound as a morpheme in the phonological system.56. back-formation: an abnormal type of word-formation where a shorter word is derived by deleting an imagined affix from a long form already in the language.57. assimilation: the change of a sound as a result of the influence of an adjacent sound,which is more specificallycalled.”contact”or”contiguous”assimilation.58. dissimilation: the influence exercised.By one sound segment upon the articulation of another, so that the sounds become less alike,or different.59. folk etymology: a change in form of a word or phrase,resulting from an incorrect popular nation of the origin or meaning of the term or from the influence of more familiar terms mistakenly taken to be analogous 60. category:parts of speech and function,such as the classification of words in terms of parts of speech,the identification of terms of parts of speech,the identification of functions of words in term of subject,predicate,etc.61. concord: also known as agreement,is the requirement that the formsof two or more words in a syntactic relationship should agree with each other in terms of some categories.62. syntagmatic relation between one item and others in a sequence,or between elements which are all present.63. paradigmatic relation: a relation holding between elements replaceable with each other at a particular place in a structure,or between one element present and he others absent.64. immediate constituent analysis: the analysis of a sentence in terms of its immediate constituents---word groups(or phrases),which are in trun analyzed into the immediate constituents of their own,and the process goes on until the ultimate constituents are reached.65. endocentric construction: one construction whose distribution is functionally equivalent,or approaching equivalence,to one of its constituents,which serves as the centre,or head, of the whole.Hence an endocentric construction is also known as a headed construction.66. exocentric construction: a construction whose distribution is not functionally equivalent to any to any of its constituents.67. deep structure: the abstract representation of the syntactic properties of a construction,i.e.the underlying level of structural relations between its different constituents ,such sa the relation between,the underlying subject and its verb,or a verb and its object.68. surfacte structure: the final stage in the syntactic derivation ofa construction,which closely corresponds to the structural organization of a construction people actually produce and receive.69. c-command: one of the similarities, or of the more general features, in these two government relations, is technically called constituent command,c-command for short.70. government and binding theory: it is the fourth period of development Chomsky’s TG Gram mar, which consists of X-bar theme: the basis,or the starting point, of the utterance.71. communicative dynamism: the extent to which the sentence element contributes to the development of the communication.72. ideational function: the speaker’s expe rience of the real world,including the inner world of his own consciousness.73. interpersonal function: the use of language to establish and maintain social relations: for the expression of social roles,which include the communication roles created by language itself;and also for getting things done,by means of the interaction between one person and another..74. textual function: the use of language the provide for making links with itself and with features of the situation in which it is used. 75. conceptual meaning: the central part of meaning, which contains logical,cognitive,or denotative content.76. denotation: the core sense of a word or a phrade that relates itto phenomena in the real world.77. connotation: a term in a contrast with denotation,meaning the properties of the entity a word denotes.78. reference: the use of language to express a propostion,meaning the properties of the entity a word denotes.79. reference: the use of anguage to express a proposition,i.e. to talk about things in context.80. sense: the literal meaning of a word or an expression,independent of situational context.81. synonymy: is the technical name for the sameness relation.82. complentary antonymy: members of a pair in complementary antonymy are complementary to each field completely,such as male,female,absent.83. gradable antongymy: members of this kind are gradable,such as long:short,big;small,fat;thin,etc.84. converse antonymy: a special kind of antonymy in that memembers ofa pair do not constitute a positive-negative opposition,such asbuy;sell,lend,borrow,above,below,etc.85. relational opposites:converse antonymy in reciprocal social roles,kinship relations,temporal and spatial relations.There are always two entities involved.One presupposes the other. Theshorter,better;worse.etc are instances of relational opposites.86. hyponymy: a relation between tow words,in which the meaning of one word(the superordinate)is included in the meaning of another word(the hyponym)87. superordinate: the upper term in hyponymy,i.e.the class name.A superordinate usually has several hyponyms.Under animal,for example,there are cats,dogs,pigs,etc,88. semantic component: a distinguishable element of meaning in a word with two values,e.g<+human>89. compositionality: a principle for sentence analysis, in which the meaning of a sentence depends on the meanings of the constituent words and the way they are combined.90. selection restriction:semantic restrictions of the noun phrases that a particular lexical item can take,e.g.regret requires a human subject.91. prepositional logic: also known as prepositional calculus or sentential calculus,is the study of the truth conditions for propositions:how the truth of a composite propositions and the connection between them.92. proposition;what is talk about in an utterance,that part of the speech act which has to do with reference.93. predicate logic: also predicate calculus,which studies the internal structure of simple.94. assimilation theory: language(sound,word,syntax,etc)change orprocess by which features of one element change to match those of another that precedes or follows.95. cohort theory: theory of the perception of spoken words proposed in the mid-1980s.It saaumes a “recognition lexicon”in which each word is represented by a full and independent”recognistion element”.When the system receives the beginning of a relevant acoustic signal,all elements matching it are fully acticated,and,as more of the signal is received,the system tries to match it independently with each of them,Wherever it fails the element is deactivated;this process continues until only one remains active.96. context effect: this effect help people recognize a word more readily when the receding words provide an appropriate context for it.97. frequency effect: describes the additional ease with which a word is accessed due to its more frequent usage in language.98. inference in context: any conclusion drawn from a set of proposition,from something someone has said,and so on.It includes things that,while not following logically,are implied,in an ordinarysense,e.g.in a specific context.99. immediate assumption: the reader is supposed to carry out the progresses required to understand each word and its relationship to previous words in the sentence as soon as that word in encountered. 100. language perception:language awareness of things through the physical senses,esp,sight.101. language comprehension: one of the three strand of psycholinguistic research, which studies the understanding of language.102. language production: a goal-directed activity, in the sense that people speak and write in order to make friends, influence people, convey information and so on.103. language production: a goal-directed activity, in the sense that people speak and write in order to make friends, influence people, convey information and so on.104. lexical ambiguity: ambiguity explained by reference to lexical meanings: e.g. that of I saw a bat, where a bat might refer to an animal or, among others, stable tennis bat.105. macro proposition: general propositions used to form an overall macrostructure of the story. 106. modular: which a assumes that the mind is structured into separate modules or components, each governed by its own principles and operating independently of others.107. parsing: the task of assigning words to parts of speech with their appropriate accidents, traditionally e.g. to pupils learning lat in grammar.108. propositions: whatever is seen as expressed by a sentence which makes a statement. It is a property of propositions that they have truth values.109. psycholinguistics: is concerned primarily with investigating the psychological reality of linguistic structure. Psycholinguistics can be divided into cognitive psycholinguistics(being concerned above all with making inferences about the content of human mind, and experimental psycholinguistics(being concerned somehow with empirical matters, such as speed of response to a particular word).110. psycholinguistic reality: the reality of grammar, etc. as a purported account of structures represented in the mind of a speaker. Often opposed, in discussion of the merits of alternative grammars, to criteria of simplicity, elegance, and internal consistency.111. schemata in text: packets of stored knowledge in language processing.112. story structure: the way in which various parts of story are arranged or organized.113. writing process: a series of actions or events that are part of a writing or continuing development.114. communicative competence: a speaker’s knowledge of the total set of rules, conventions, etc. governing the skilled use of language in a society. Distinguished by D.Hymes in the late 1960s from Chomsley’s concept o f competence, in the restricted sense of knowledge of a grammar.115. gender difference: a difference in a speech between men and women is”genden difference”116. linguistic determinism: one of the two points in Sapir-Whorf hypothesis,nguage determines thought.117. linguistic relativity: one of the two points in Spir-Whorf hypotheis,i.e.there’s no limit to the structural diversity of languages.118. linguistic sexism:many differences between me and women in language use are brought about by nothing less than women’s place in society.119. sociolinguistics of language: one of the two things in sociolinguistics,in which we want to look at structural things by paying attention to language use in a social context.120. sociolinguistics of society;one of the two things in sociolinguistics,in which we try to understand sociological things of society by examining linguistic phenomena of a speaking community.121. variationist linguistics: a branch of linguistics, which studies the relationship between speakers’ social starts and phonological variations.122. performative: an utterance by which a speaker does something does something, as apposed to a constative, by which makes a statement which may be true or false.123. constative: an utterance by which a speaker expresses a proposition which may be true or false.124. locutionary act: the act of saying something; it’s an act of conveying literal meaning by means of syntax, lexicon, and phonology. Namely., the utterance of a sentence with determinate sense and reference.125. illocutionary act: the act performed in saying something; its force is identical with the speaker’s intention.126. perlocutionary act: the act performed by or resulting from saying something, it’s the consequence of, or the change brought about by the utterance.127. conversational implicature: the extra meaning not contained in the literal utterances, understandable to the listener only when he shares the speaker’s knowledge or knows why and how he violates intentionally one of the four maxims of the cooperative principle.128. entailment: relation between propositions one of which necessarily follows from the other :e.g.”Mary is running” entails, among other things,”Mary is not standing still”.129. ostensive communication: a complete characterization of communication is that it is ostensive-infer-entail.130. communicative principle of relevance: every act of ostensive communicationcommunicates the presumption of its own optimal relevance.131. relevance: a property that any utterance, or a proposition that it communicates, must, in the nature of communication, necessarily have.132. Q-principle: one of the two principles in Horn’s scale,i.e. Make your contribution necessary (G.Relation,Quantity2,Manner);Say no more than you must(given Q).133. division of pragmatic labor: the use of a marked relatively complex and/or expression when a corresponding unmarked a(simpler, less “effortful”)alternate expression is available tends to be interpreted as conveying a marked message(one which the unmarked alternative would not or could not have conveyed).134. constraints on Horn scales: the hearer-based o-Principle is a sufficiency condition in the sense that information provided is the most the speaker is able to..135. third-person narrator: of the narrator is not a character in the fictional world, he or she is usually called a third –person narrator.136. I-narrator: the person who tells the story may also be a character in the fictional world of the story, relating the story after the event.137. direct speech: a kind of speech presentation in which the character said in its fullest form.138. indirect speech: a kind of speech presentation in which the character said in its fullest form.139. indirect speech: a kind of speech presentation which is an amalgam of direct speech.140. narrator’s representation of speech acts: a minimalist kind of presentation in which a part of passage can be seen as a summery of a longer piece of discourse, and therefore even more backgrounder than indirect speech representation would be.141. narrator” representation of thought acts: a kind of categories used by novelists to represent the thoughts of their of characters are exactly as that used to present speech acts. For example, she considered his unpunctuality.142. indirect thought: a kind of categories used by novelist to represent the thoughts of their characters are exactly as that used to present indirect speech .For example, she thought that he would be late.143. fee indirect speech: a further category which can occur, which is an amalgam of direct speech and indirect speech features.144. narrator’s representation of thought acts: a kind of the categories used by novelists to present the thoughts of their characters are exactly the same as those used to represent a speech e.g. He spent the day thinking.145. indirect thought: a kind of categories used by novelist to represent the thoughts of their characters are exactly as that used to present indirect speech. For example, she thought that he would be late.146. fee indirect speech: a further category which can occur, which is an amalgam of direct speech and indirect speech features.147. narrator’s representation of thought: the ca tegories used by novelists to present the thoughts of their characters are exactly the same as those used to represent a speech e.g. He spent the day thinking.148. free indirect thought: the categories used by novelists to represent the thoughts of their characters are exactly the same as those used to represent a speech, e.g. He was bound to be late.149. direct thought: categories used by novelists to represent the thoughts of their characters are exactly the same as those used to represent a speech..150. computer system: the machine itself together with a keyboard, printer, screen, disk drives ,programs, etc.151. computer literacy: those people who have sufficient knowledge and skill in the use of computers and computer software.152. computer linguistics: a branch of applied linguistics ,dealing with computer processing of human language.153. Call: computer-assisted language learning(call),refers to the use of a computer in the teaching or learning of a second or foreign language.154. programmed instruction: the use of computers to monitor student progress, to direct students into appropriate lessons, material, etc.155. local area network: are computers linked together by cables in a classroom, lab, or building. They offer teachers a novel approach for creating new activities for students that provide more time and experience with target language.156. CD-ROM: computer disk-read only memory allows huge amount of information to be stored on one disk with quich access to the information. Students and teachers can access information quickly and efficiently for use in and out of the classroom.157. machine translation: refers to the use of machine(usually computer)to translate texts from one language to another.158. concordance: the use of computer to search for a particular word, sequence of words. or perhaps even a part of speech in a text. The computer can also receive all examples of a particular word, usually in a context ,which is a further aid to the linguist .It can also calculate the number of occurrences of the word so that information on the frequency of the word may be gathered. 159. annotation: if corpora is said to be unannotated-it appears in its existing raw state of plain text, whereas annotated corpora has been enhanced with various type of linguistic information, 160. annotation: if corpora is said to be unannotated—it appears in its existing raw state of plain text, whereas annotated corpora has been enhanced with various type of linguistic information. 161. informational retri: the term conventionally though somewhat inaccurately, applied to the type of actrvity discussed in this volume.An information retri system does not infor(i.e.change the knowledge of)the user on the subject of his inquiry.it merely informs on the existence(ornon-existence)and whereabouts of documents relating to his request.162. document representative: information structure is concerned with exploiting relationships,between documents to improve the efficiency and effectiveness of retri strategies.It covers specifically a logical organization of information,such as document representatives,for the purpose of information retri.163. precision: the proportion of retri documents which are relevant.164. recall: the proportion of retri documents which are relevant.165. applied linguistics: applications of linguistics to study of second and foreign language learning and teaching,and other areas such as translation,the compiling of dictionaries,etc166. communicative competence: as defined by Hymes,the knowledge and ability involved in putting language to communicative use.167. syllabus:the planning of course of instruction.It is a description of the cousr content,teaching procedures and learning experiences.168. interlanguage:the type of language constructed by second or foreign language learners who are still in the process of learning a language,i.e.the language system between the target language and the learner’s native language.169. transfer: the influence of mother tongue upon the second language.When structures of the two languages are similar,we can get positive transfer of facilitation;when the two languages are different in structures,negative transfer of inference occurs and result in errors.170. validity: the degree to which a test meansures what it is meant to measure.There are four kinds of validity,i.e.content validity,construct validity,empirical valiodity,and face validity.171. rebiability: can be defined as consistency.There are two kinds of reliability,i.e.stability reliability,and equiralence reliability.172. hypercorrection: overuse of a standard linguistic features,in terms of both frequency,i.e.overpassing the speakers of higher social status,and overshooting the target,i.e.extending the use of a form inalinguistic environment where it is not expected to occur,For example,pronouncing ideas as[ai’dier],extending pronouncing post-vocalic/r/ in an envorienment where it’s not supposed to occur.173. discrete point test: a kind of test in which language structures or skills are further divided into individual points of phonology,syntax and lexis.174. integrative test: a kind of test in which language structures or skills are further divided into individual points of phonology, syntax and lexis.。

自我与他者——拉康理论视域下的《傲慢与偏见》

自我与他者——拉康理论视域下的《傲慢与偏见》
本文将运用雅克·拉康的镜像理论及三界说(想象界、象征界、真实界)揭示这一 复杂变化的过程。拉康无疑是 20 世纪中叶法国弗洛伊德学派的翘楚,同时也是解构主 义浪潮下的领军者,两位不同时代的作家二百年的遥相呼应将赋予《傲慢与偏见》这部 作品新的意义。本文以主人公伊丽莎白自我的发展过程为主线,探究主人公自我的形成 到重构,以致最终失落的全过程。作品通过主人公对自己、对人世的逐步把握揭露了一 个不稳定的自我,多重矛盾作用下的结果是主体的破碎和自我的崩析。在现代社会里, 自我的分裂和摆动尤为剧烈,脱离了原始稳定自我的人们越发感到惶恐,大写他者对每 个人的碾压使得人人都与真正的自我疏离、隔绝了,当今具有时代性的命题,在十八世 纪末便由奥斯丁涉笔。本文便从这一视角切入,意在透析作品的表层结构,还原作家的 真意和作品的真谛。
在此本人郑重承诺:所呈交的学位论文不存在舞弊作伪行为,文责自负。
学位申请人(学位论文作者)签名:
201 年 月 日
关于学位论文著作权使用授权书
本人经河南大学审核批准授予硕士学位。作为学位论文的作者,本人完全了解并同 意河南大学有关保留、使用学位论文的要求,即河南大学有权向国家图书馆、科研信息 机构、数据收集机构和本校图书馆等提供学位论文(纸质文本和电子文本)以供公众检 索、查阅。本人授权河南大学出于宣扬、展览学校学术发展和进行学术交流等目的,可 以采取影印、缩印、扫描和拷贝等复制手段保存、汇编学位论文(纸质文本和电子文本)。
关键词:简·奥斯丁,《傲慢与偏见》,自我,他者,拉康
I
ABSTRACT
Jane Austen,lived in the early eighteenth century. She swept the popular sentimentalism and Gothic novels, created a fresh wind of realism uniquely. Her works are mostly described the rural life has not been eroded by industrial revolution and capitalism, showing the marriage between ladies and gentlemen.

Neuroimmunoendocrinology

Neuroimmunoendocrinology

Department of Immunology
细胞因子对痛觉的调节
IFN-α 具有中枢镇痛作用,这种作用可被纳 洛酮所阻断或反转。 IL-2具有中枢和外周镇痛作用,这种作用也可 被纳洛酮所阻断或反转。 机理: IFN-α , IL-2 内源性阿片肽 的释放 镇痛
Department of Immunology
Department of Immunology
About the History
(1907-1982)
Department of Immunology
About the History
50年代后中枢毁损方法在神经生理学应用 年代后中枢毁损方法在神经生理学应用 1972年原苏联学者 年原苏联学者Korneva等发现机体接受抗原刺激后, 等发现机体接受抗原刺激后, 年原苏联学者 等发现机体接受抗原刺激后 脑内某些区域神经元放电发生改变 瑞士学者Basedovasky 等实验也得到了类似的结果 瑞士学者 80年代 年代Blalock提出神经免疫内分泌网络 年代 提出神经免疫内分泌网络 (neuroimmunoendocrine network)
Department of Immunology
细胞因子对内分泌的调节
生长激素释放激素(GHRH) 生长激素释放激素 促性腺激素释放激素( 促性腺激素释放激素(GnRH) ) IL-1 促肾上腺皮质激素释放激素(CRF) 促肾上腺皮质激素释放激素( ) 促甲状腺激素( 促甲状腺激素(TSH) ) 催乳素 (PRL) )
Department of Immunology
内分泌系统对神经系统、 内分泌系统对神经系统、免疫系统的调节
免疫组化实验结果显示: 免疫组化实验结果显示:神经细胞膜和细胞 质中存在着几乎所有内分泌激素的受体。 质中存在着几乎所有内分泌激素的受体。 各种激素分别作用不同的神经元,产生生理 各种激素分别作用不同的神经元, 活动的改变。 活动的改变。 免疫细胞上也有多种激素受体。 免疫细胞上也有多种激素受体。

皮尔士符号学观照下的三位一体翻译观

皮尔士符号学观照下的三位一体翻译观

作者: 杨镇源[1,2]
作者机构: [1]四川大学,四川成都610064;[2]电子科技大学,四川成都610054
出版物刊名: 贵州社会科学
页码: 32-35页
主题词: 符号的三性;三位一体;合同性;还翻译以生命
摘要:翻译研究经历过的三种主流研究范式(语文学范式、结构主义语言学范式、解构主义范式)都未能真正揭示翻译这种交际行为的生命力。

皮尔士符号学中“符号一对象一解释项”三位一体的合同性指号模式对翻译研究有着重大启示:它使研究者克服了以往三种范式对符号第一性、第二性和第三性的分别偏颇。

我们也由此认识到翻译在共识性真理观下的阐释多样性,即翻译在维持其本体的前提下焕发的勃勃生机,从而“还翻译以生命”。

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a rXiv:089.2215v2[mat h.A T]23Se p28COHOMOLOGICAL NON-RIGIDITY OF GENERALIZED REAL BOTT MANIFOLDS OF HEIGHT 2MIKIYA MASUDA Abstract.We investigate when two generalized real Bott manifolds of height 2have isomorphic cohomology rings with Z /2coefficients and also when they are diffeomorphic.It turns out that cohomology rings with Z /2coefficients do not distinguish those manifolds up to diffeo-morphism in general.This gives a counterexample to the cohomological rigidity problem for real toric manifolds posed in [5].We also prove that generalized real Bott manifolds of height 2are diffeomorphic if they are homotopy equivalent. 1.Introduction A toric manifold is a compact smooth toric variety and a real toric mani-fold is the set of real points of a toric manifold.In [7]we asked whether toric manifolds are diffeomorphic if their cohomology rings with Z coefficients are isomorphic as graded rings,which is now called cohomological rigidity prob-lem for toric manifolds .No counterexample and some partial affirmative solutions are known to the problem (see [3],[7]).If X is a toric manifold and X (R )is the real toric manifold associated to X ,then H ∗(X (R );Z /2)is isomorphic to H 2∗(X ;Z )⊗Z /2as graded rings.Motivated by this,we posed in [5]the following analogous problem.Cohomological rigidity problem for real toric manifolds.Are two real toric manifolds are diffeomorphic if their cohomology rings with Z /2coefficients are isomorphic as graded rings?We say that cohomological rigidity over Z /2holds for a family of closed smooth manifolds if the manifolds in the family are distinguished up todiffeomorphism by their cohomology rings with Z /2coefficients.A real Bott manifold is the total space of an iterated R P 1bundles where each R P 1bundle is the projectivization of a Whitney sum of two real line bundles.A real Bott manifold is not only a real toric manifold but also a compact flat riemannian manifold.We proved in [5](and [6])that cohomological rigidity over Z /2holds for the family of real Bott manifolds.2M.MASUDAIn this paper we consider real toric manifolds obtained as the total spaces of projectivization of Whitney sums of real line bundles over a real projective space.We call such a real toric manifold a generalized real Bott manifold of height2.In this paper we will investigate when those two manifolds have isomorphic cohomology rings with Z/2coefficients and also when they are diffeomorphic.As a result,we will see that cohomological rigidity over Z/2 fails to hold for some family of generalized real Bott manifolds of height2, which gives a negative answer to the cohomological rigidity problem for real toric manifolds above.We also prove that generalized real Bott manifolds of height2are diffeomorphic if they are homotopy equivalent.The author thanks Y.Nishimura for pointing out a mistake in an earlier version of this paper and T.Panov for his comments.2.Cohomological conditionLet a,b be positive integers and wefix them.Letγbe the tautological line bundle over R P a−1and let1denote a trivial real line bundle over an appropriate space.For a real vector bundle E,we denote by P(E)the total space of the projectivization of E.For an integer q such that0≤q≤b,we setM(q):=P(qγ⊕(b−q)1).Note that(2.1)M(q)is diffeomorphic to M(b−q)because P(E⊗L)and P(E)are diffeomorphic for any smooth vector bundle E and line bundle L over a smooth manifold.A simple computation shows that(2.2)H∗(M(q);Z/2)=Z/2[x,y]/(x a,(x+y)q y b−q)where x is the pullback of thefirst Stiefel-Whitney class ofγto M(q)and y is thefirst Stiefel-Whitney class of the tautological line bundle over M(q). One easily sees that a set{x i y j|0≤i<a,0≤j<b}is an additive basis of H∗(M(q);Z/2).Lemma2.1.If0<q<b,then both y a and(x+y)a are non-zero. Proof.Suppose y a=0.Then it follows from(2.2)that there are constants c,d∈Z/2and a homogeneous polynomial f(x,y)in x,y over Z/2such thaty a= cx a if a<bdx a+f(x,y)(x+y)q y b−q if a≥bas polynomials in x,y.Clearly the former does not occur and the latter also does not occur because q>0by assumption.This is a contradiction, so y a=0.If we set X=x and Y=x+y,then x+y=Y and y=X+Y,so that the role of x and x+y will be interchanged.Since b−q>0by assumption, the above argument applied to Y instead of y proves that(x+y)a=0.REAL GENERALIZED BOTT MANIFOLDS OF HEIGHT23 Definition.h(a):=min{n∈N∪{0}|2n≥a}.For example,h(1)=0,h(2)=1,h(3)=h(4)=2,h(5)=h(6)=h(7)=h(8)=3, h(9)=···=h(16)=4,....Lemma 2.2.Let q and q′be non-negative integers.Then q′i ≡ q i (mod2)for0≤∀i<a if and only if q′≡q(mod2h(a)),where n m is understood to be0when n<m as usual.Proof.When q′=q,the lemma is trivial.We may assume that q′>q without loss of generality.We note that the former congruence relations in the lemma are equivalent to the following congruence relation of polynomials in t with Z/2coefficients:(2.3)(1+t)q′−q≡1(mod t a).We shall prove the“if”partfirst.Suppose q′≡q(mod2h(a)).Then q′−q=2h(a)R with some positive integer R and the left hand side of(2.3) turns into(1+t)q′−q=(1+t2h(a))R≡1(mod t a)where the last congruence relation holds because2h(a)≥a.This verifies (2.3).We shall prove the“only if”part by induction on a.When a=1, 2h(a)=1and hence the congruence relation q′≡q(mod2h(a))trivially holds.Suppose that the induction assumption is satisfied for a−1with a≥2and that(2.3)holds for a.Then(2.3)holds for a−1,so the induction assumption implies q′≡q(mod2h(a−1)).When a−1is not a power of2, h(a−1)=h(a);so the congruence relation q′≡q(mod2h(a))holds for a. When a−1is a power of2,say2s,h(a−1)=s,h(a)=s+1and q′−q=2s Q with some positive integer Q because q′≡q(mod2h(a−1)). Therefore(1+t)q′−q=(1+t2s)Q=1+Qt2s+higher degree terms.Since this is congruent to1modulo t a and a>2s=a−1,Q must be even. This shows that q′≡q(mod2s+1),proving the induction assumption for a because s+1=h(a).This completes the induction step and proves the “only if”part. Theorem2.3.Let0≤q,q′≤b.Then H∗(M(q);Z/2)and H∗(M(q′);Z/2) are isomorphic as graded rings if and only if q′≡q or b−q(mod2h(a)). Proof.If both q and q′are in{0,b},then the theorem is trivial.So we may assume0<q<b without loss of generality.We denote by x′and y′the generators in H∗(M(q′);Z/2)corresponding to x and y.4M.MASUDAThe“if”part easily follows from(2.2)and Lemma2.2.We shall prove the“only if”part.Suppose that there is an isomorphismϕ:H∗(M(q′);Z/2)→H∗(M(q);Z/2)as graded rings.Sinceϕ(x′)a=ϕ(x′a)=0,ϕ(x′)is neither y nor x+ y by Lemma2.1.Thereforeϕ(x′)=x and henceϕ(y′)=y or x+y. Supposeϕ(y′)=y.(Whenϕ(y′)=x+y,the role of q and b−q will be interchanged.)Then(x′+y′)q′y′b−q′maps to(x+y)q′y b−q′byϕand it is zero in H∗(M(q);Z/2),so there are constants c,d∈Z/2and a homogeneous polynomial f(x,y)in x,y over Z/2such that(x+y)q′y b−q′= c(x+y)q y b−q in case a>bd(x+y)q y b−q+f(x,y)x a in case a≤bas polynomials in x,y.Clearly c is non-zero,so c=1.Therefore q′=q in case a>b.If d=0,then the right-hand side of the identity above in case a≤b is divisible by x as a≥1while the left-hand side is not.Therefore d=1and the identity above in case a≤b implies the former congruence relations in Lemma2.2by comparing the coefficients of x i y b−i for i<a;so q′≡q(mod2h(a))by Lemma2.2. Corollary2.4.Cohomological rigidity over Z/2holds for M(q)’s if b≤2h(a).Proof.Suppose that M(q)and M(q′)have isomorphic cohomology rings with Z/2coefficients.Then q and q′must satisfy the congruence relation in Theorem2.3.But since b≤2h(a),the congruence implies that q′=q or b−q.This together with(2.1)shows that M(q′)is diffeomorphic to M(q).3.KO theoretical conditionIn this section,we use KO theory to deduce a necessary and sufficient condition on q and q′for M(q)and M(q′)to be diffeomorphic.We begin with a general lemma.Lemma3.1.Let E→X be a real smooth vector bundle over a smooth manifold X.Letπ:P(E)→X be the associated real projective bundle and letηbe the tautological real line bundle over P(E).Then the tangent bundle τP(E)of P(E)with1added is isomorphic to Hom(η,π∗(E))⊕π∗(τX). Proof.A pointℓof P(E)is a line in E and thefibers ofηoverℓare vectors in the lineℓ,soηis a subbundle ofπ∗(E).We give afiber metric on E. It induces afiber metric onπ∗(E)and we denote byη⊥the orthogonal complement ofηinπ∗(E).Thenτf P(E)the tangent bundle along the fiber ofπ:P(E)→X is isomorphic to Hom(η,η⊥).This is proved in[8, Lemma4.4]when X is a point and the same argument works for any X. In fact,the argument is as follows.We note that the unit S0bundle S(η) ofηcan naturally be identified with the unit sphere bundle S(E)of E.LetREAL GENERALIZED BOTT MANIFOLDS OF HEIGHT 25v ∈S (η)be in the fiber over ℓ∈P (E ),that is,v is a vector in the line ℓwith unit length.To an element ψ∈Hom(η,η⊥)over ℓ∈P (E ),we assign ψ(v ).It is tangent to the fiber of S (E )over π(ℓ)∈X at v ∈S (E )=S (η)and ψ(−v )=−ψ(v ),so ψ(v )defines an element of τf P (E )over ℓ.This correspondence gives an isomorphism from Hom(η,η⊥)to τf P (E ).Thus we obtainτf P (E )⊕1∼=Hom(η,η⊥)⊕Hom(η,η)∼=Hom(η,π∗(E )).This implies the lemma because τP (E )∼=τf P (E )⊕π∗(τX ).Definition.k (a ):=#{n ∈N |0<n <a and n ≡0,1,2,4(mod 8)}.For example,k (1)=0,k (2)=1,k (3)=k (4)=2,k (5)=k (6)=k (7)=k (8)=3,k (9)=4,k (10)=5,k (11)=k (12)=6,...It is known that KO(R P a −1)is a cyclic group of order 2k (a )generated by γ−1([1,Theorem 7.4]).This implies that 2k (a )γis trivial because the fiber dimension (that is 2k (a ))is strictly larger than the dimension of the base space (that is a −1).Theorem 3.2.Let 0≤q,q ′≤b .Then M (q )and M (q ′)are diffeomorphic if and only if q ′≡q or b −q (mod 2k (a )).Proof.We shall prove the “if”part first.If 2k (a )≥b (this is the case when a ≥b ),then q ′=q or b −q and hence M (q )∼=M (q ′)by (2.1).Suppose 2k (a )<b .Then a <b so that the bundles q ′γ⊕(b −q ′)1and qγ⊕(b −q )1are in the stable range and these bundles are isomorphic because KO(R P a −1)is a cyclic group of order 2k (a )generated by γ−1and q ′≡q (mod 2k (a )).Hence M (q )∼=M (q ′).We shall prove the “only if”part.Suppose M (q )∼=M (q ′)and let f :M (q )→M (q ′)be a diffeomorphism.Thenf ∗(τM (q ′))=τM (q )in KO (M (q )).Since τ(R P a −1)⊕1∼=aγ,it follows from Lemma 3.1that the identity above implies f ∗ Hom(η′,q ′γ⊕(b −q ′)1)⊕aγ =Hom(η,qγ⊕(b −q )1)⊕aγin KO (M (q ))(3.1)where ηand η′denote the tautological line bundles over M (q )and M (q ′)respectively and γis regarded as a line bundle over M (q )and M (q ′)through the projections onto R P a −1.If both q and q ′are in {0,b },then the “only if”part is obviously satisfied.Therefore we may assume that 0<q <b .Then f ∗(x ′)=x and f ∗(y ′)=y or x +y by Lemma 2.1.Therefore f ∗(γ)=γand f ∗(η′)=ηor γη.Suppose6M.MASUDAf∗(η′)=ηoccurs.(When f∗(η′)=γηoccurs,the role of q and b−q will be interchanged.)Then(3.1)reduces toHom(η,q′γ⊕(b−q′)1)=Hom(η,qγ⊕(b−q)1)in KO(M(q)). Thefibration M(q)→R P a−1has a cross-section and we send the identity above to KO(R P a−1)through the cross-section.Thenηbecomes trivial or γbecause a line bundle over R P a−1is either trivial orγ.In any case,the identity above reduces to(3.2)(q′−q)(γ−1)=0in KO(R P a−1)and this implies q′≡q(mod2k(a)). One easily sees that h(a)≤k(a)for any a and the equality holds if and only if a≤9.Corollary2.4can be improved as follows.Theorem3.3.Cohomological rigidity over Z/2holds for M(q)’s if and only if a≤9or b≤2h(a).Proof.If a≤9,then h(a)=k(a).So the“if”part follows from Theo-rems2.3and3.2when a≤9and from Corollary2.4when b≤2h(a). Suppose a≥10(so k(a)>h(a)≥4)and b>2h(a).Then we take(q,q′)= (1,2h(a)+1)when b is a multiple of2h(a),(0,2h(a))when b is not a multiple of2h(a).In both cases above,q′≡q(mod2h(a))but q′is not congruent to neither q nor b−q modulo2k(a)since k(a)>h(a)≥4.Therefore M(q)and M(q′)are not diffeomorphic by Theorem3.2while they have isomorphic cohomology rings with Z/2coefficients by Theorem2.3.4.Homotopical rigidityCohomological rigidity over Z/2does not hold for M(q)’s in general,but the following holds.Theorem4.1.If M(q)and M(q′)are homotopy equivalent,then they are diffeomorphic.Proof.For afinite CW complex X,J(X)denotes the J group of X and J: KO(X)→J(X)denotes the J homomorphism.Let f:M(q)→M(q′) be a homotopy equivalence.ThenJ(f∗(τM(q′)))=J(τM(q))in J(M(q))by a theorem of Atiyah([2,Theorem3.6]).The same argument as in the latter part of the proof of Theorem3.2shows that we may assume that 0<q<b and f∗(η′)=η,and thenJ (q′−q)(γ−1) =0in J(R P a−1). This implies(3.2)because J: KO(R P a−1)→J(R P a−1)is an isomorphism (see[4,Theorem13.9]).Hence M(q)and M(q′)are diffeomorphic.REAL GENERALIZED BOTT MANIFOLDS OF HEIGHT27 Theorem4.1motivates us to ask whether two real toric manifolds are diffeomorphic(or homeomorphic)if they are homotopy equivalent,which we may call homotopical rigidity problem for real toric manifolds.References[1]J.F.Adams,Vectorfields on spheres,Ann.of Math.75(1962),603–632.[2]M.F.Atiyah,Thom complexes,Proc.London Math.Soc.(3)11(1961),291–310.[3]S.Choi,M.Masuda and D.Y.Suh,Topological classification of generalized Botttowers,preprint,arXiv:0807.4334.[4]D.Husemoller,Fiber Bundles,Third Edition,Graduate Texts in Math.20,Springer-Verlag1993.[5]Y.Kamishima and M.Masuda,Cohomological rigidity of real Bott manifolds,preprint,arXiv:0807.4263.[6]M.Masuda,Classification of real Bott manifolds,preprint,arXiv:0809.2178.[7]M.Masuda and D.Y.Suh,Classification problems of toric manifolds via topology,Proc.of Toric Topology,Contemp.Math.460(2008),273–286,arXiv:0709.4579. [8]nor and J.D.Stasheff,Characteristic Classes,Ann.of Math.Studies76,Princeton Univ.Press1974.Department of Mathematics,Osaka City University,Sugimoto,Sumiyoshi-ku,Osaka558-8585,JapanE-mail address:masuda@sci.osaka-cu.ac.jp。

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