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2011Tell Me a Good Story and I may lend you money,the role of narratives in peer-to-peer decisions

2011Tell Me a Good Story and I may lend you  money,the role of narratives in peer-to-peer decisions

MICHAL HERZENSTEIN,SCOTT SONENSHEIN,and UTPAL M.DHOLAKIAThis research examines how identity claims constructed in narrativesby borrowers influence lender decisions about unsecured personal loans.Specifically,do the number of identity claims and their content influ-ence lending decisions,and can they predict the longer-term perfor-mance of funded loans?Using data from the peer-to-peer lending website,the authorsfind that unverifiable information affects lendingdecisions above and beyond the influence of objective,verifiable informa-tion.As the number of identity claims in narratives increases,so doesloan funding,whereas loan performance suffers,because these borrow-ers are less likely to pay back the loan.In addition,identity content playsan important role.Identities focused on being trustworthy or successfulare associated with increased loan funding but ironically are less predic-tive of loan performance than other identities(i.e.,moral and economichardship).Thus,some identity claims aim to mislead lenders,whereasothers provide true representations of borrowers.Keywords:identities,narratives,peer-to-peer lending,decision makingunder uncertainty,consumerfinancial decision making Tell Me a Good Story and I May Lend Y ou Money:The Role of Narratives inPeer-to-Peer Lending DecisionsThe past decade has witnessed a growing number of business models that facilitate economic exchanges between individuals with limited institutional mediation. Consumers can buy products on eBay,lend money on peer-to-peer(P2P)loan auction sites such as , and provide zero-interest“social loans”to entrepreneurs through .In all these cases,strangers decide whether to engage in an economic exchange and on what terms,using only information provided by the borrowers. *Michal Herzenstein is Assistant Professor of Marketing,Lerner College of Business and Economics,University of Delaware(e-mail: michalh@).Scott Sonenshein is Assistant Professor of Man-agement,Jones Graduate School of Business,Rice University(e-mail: scotts@).Utpal M.Dholakia is Professor of Management, Jones Graduate School of Business,Rice University(e-mail:dholakia@ ).The authors thank Rick Andrews,Richard Schwarz,and Greg Hancock for their statistical assistance.They further thank the editor John Lynch,the associate editor,and the two JMR reviewers for their insight-ful comments.Financial support from the Lerner College of Business and Economics at the University of Delaware and the Jones Graduate School of Business at Rice University is greatly appreciated.David Mick served as associate editor for this article.Objective quantitative data about exchange partners often are difficult to obtain,insufficient,or unreliable.As a result, decision makers may turn to subjective,unverifiable,but potentially diagnostic qualitative data(Michels2011). One form of qualitative data useful to decision makers in such economic exchanges are the narratives constructed by potential exchange partners.A narrative is a sequentially structured discourse that gives meaning to events that unfold around the narrator(Riessman1993).For example,a narra-tive might explain a person’s past experiences,current sit-uation,or future hopes(e.g.,Thompson1996;Wong and King2008).By providing an autobiographical sketch that explains the vicissitudes of their life,the narrative authors provide a window into how they conceptualize themselves (Gergen and Gergen1997)and a portrait of how they con-struct their identity.However,as a result of either ambiguity or the strategic use of the medium to influence others(e.g., Schau and Gilly2003),narratives offer only one of several possible interpretations of self-relevant events(Sonenshein 2010).As a result,narrators can relay interpretations of their circumstances that convey the most favorable identities (Goffman1959).©2011,American Marketing AssociationISSN:0022-2437(print),1547-7193(electronic)S138Journal of Marketing ResearchV ol.XLVIII(Special Issue2011),S138–S149Role of Narratives in Peer-to-Peer Lending Decisions S139RESEARCH MOTIVATIONS AND CONTRIBUTIONS The idea that narratives may involve the construction of a favorable identity poses two key questions for research. First,whereas narratives can provide diagnostic informa-tion to a decision maker who is considering an economic exchange,the veracity of the narrator’s story is difficult to determine.Because a narrative offers the possibility of describing either an authentic,full,true self or a partial, inauthentic,misleading self,potential exchange partners are left to intuit the truth of the presentation.Accordingly a key question to consider is,given their potential for diagnostic and misleading information,to what extent do narratives influence economic exchange transactions?Previous con-sumer research has largely focused on narratives of con-sumption experiences(Thompson1996)or consumption stories(Levy1981),but scholars have not examined the role of narratives in economic exchanges.We believe that narratives may be a particularly powerful lens,in that they allow the consumer to attempt to gain better control over the exchange and thus can provide a means to help con-summate the exchange.Second,to what extent do narratives affect the perfor-mance and outcomes of an economic exchange?Narrative scholars claim that the construction and presentation of a narrative can shape its creator’s future behavior(Bruner 1990)but rarely examine the nature of this influence empir-ically.Such an examination would be critical to understand-ing how a mixture of quantitative and qualitative factors shapes outcome quality(e.g.,Hoffman and Yates2005). We examine these two questions using data from the online P2P loan auctions website,,by studying borrower-constructed narratives(particularly the identities embedded in them),the subsequent decisions of lenders, and transaction performance two years later.We define identity claims as the ways that borrowers describe them-selves to others(Pratt,Rockmann,and Kaufmann2006). Borrowers can construct an identity based on a range of ele-ments,such as religion or success.The elements become an identity claim when they enter public discourse as opposed to private cognition.With this framework,we make several contributions.First,by developing and testing theory around how nar-ratives supplement more objective sources of information that decision makers use when considering afinancial trans-action,we draw attention to how narrators can intentionally exploit uncertainty and favorably shape circumstantial facts to obtain resources,such as access to money in unmediated environments.The narrative,as a supplementary,yet some-times deal-making or deal-breaking,information source for decision makers is predicated on compelling stories versus objective facts.It thus offers a means for people to recon-struct their pasts and describe their futures in positive ways. Second,by linking narratives to objective performance measures,we show how narratives may predict the longer-term performance of lending decisions.Because the deci-sion stakes are high in this unmediated and unsecured financial arena,lenders engage in highly cognitive pro-cessing(Petty and Wegener1998).The strong disincen-tive of potentialfinancial loss leads to cognitive process-ing,which tends to produce accurate attributions about a person and the probabilities of future events(Osborne and Gilbert1992).Because of this motivation for accuracy,we suspect lenders use narratives to help them make invest-ment decisions.Third,from a practice perspective,the recentfinancial crisis has exposedflaws in the criteria used to make lend-ing decisions.Quantitativefinancial metrics,such as credit scores,have proven unreliable for predicting the ability or likelihood of consumers to repay unsecured loans(Feldman 2009).A narrative perspective on the consummation and performance offinancial transactions offers the promise of improving systems for assessing borrowers.RESEARCH SETTINGWe conducted our research on (hereinafter, Prosper),the largest P2P loan auction site in the United States,with more than one million members and$238mil-lion in personal loans originated since its inception in March2006(as of June2011).On Prosper,borrowers and lenders never meet in person,so we can assess the role of narratives in overcoming the uncertainty that arises during financial transactions between unacquainted actors.The process of borrowing and lending money through a loan auction on Prosper is as follows:Before posting their loan request,borrowers give Prosper permission to ver-ify relevant personal information(e.g.,household income, home ownership,bank accounts)and access their credit score from Experian,a major credit-reporting ing this and other information,such as pay stubs and income tax returns,Prosper assigns each borrower a credit grade that reflects the risk to lenders.Credit grades can range from AA, which indicates that the borrower is extremely low risk(i.e., high probability of paying back the loan),through A,B,C, D,and E to HR,which signifies the highest risk of default. Borrowers then post loan requests for auction.When post-ing their loan auctions,borrowers choose the amount(up to $25,000)and the highest interest rate they will pay.They also may use a voluntary open-text area,with unlimited space,to write anything they want—that is,the borrower’s narrative(see Michels2011).After the listing becomes active,lenders decide whether to bid,how much money to offer,and the interest rate. A$1,000loan might befinanced by one lender who lends $1,000or by40lenders,each lending$25for example. Most lenders bid the minimum amount($25)on individual loans to diversify their portfolios(Herzenstein,Dholakia, and Andrews2011).After the auction closes,listings with bids that cover the requested amount are funded.If a list-ing receives bids covering more than its requested amount, the bids with the lowest interest rates win.If the auc-tion does not receive enough bids,the request remains unfunded.Prosper administers the loan,collects payments, and receives fees of.5%to3.0%from borrowers,as well as a1%annual fee from lenders.We employed three dependent variables in our study. First,loan funding is the percentage of the loan request to receive a funding commitment from lenders.For exam-ple,if a loan request for$1,000receives bids worth$500, loan funding is50%.If it receives bids worth$2,000,loan funding equals200%.A higher loan funding value signi-fies greater lender interest.Second,percentage reduction infinal interest rate captures the decrease in the inter-est rate between the borrower’s maximum specified rate and thefinal rate.For example,if a borrower’s maximumS140JOURNAL OF MARKETING RESEARCH,SPECIAL ISSUE 2011T able 1DEFINITIONS OF IDENTITIES AND EXAMPLES FOR DATA CODINGIdentityDefinitionExamplesTrustworthy (Duarte,Siegel,and Young 2009)Lenders can trust the borrower to pay back the money on time.“I am responsible at paying my bills and lending me funds would be a good investment.”(Listing #17118)Successful (Shafir,Simonson,and Tversky 1993)The borrower is someone with a successful business or job/career.“I have [had]a very solid and successful career with an Aviation company for the last 13years.”(Listing #18608)Hardworking (Woolcock 1999)The borrower will work very hard to pay the loan back.“I work two jobs.I work too much really.I work 26days a month with both jobs.”(Listing #18943)Economic hardship (Woolcock 1999)The borrower is someone in need because of hardship,as a result of difficult circumstances,bad luck,or other misfortunes that were,or were not,under the borrower’s control.“Unfortunately,a messy divorce and an irresponsible ex have left me with awful credit.”(Listing #20525)Moral (Aquino et al.2009)The borrower is an honest or moral person.“On paper I appear to be an extremely poor financial risk.In reality,I am an honest,decent person.”(Listing #17237)Religious (Weaver and Agle 2002)The borrower is a religious person.“One night,the Lord awaken me and myspouse our business has been an enormous success with G-d on our side.”(Listing #21308)interest rate is 18%and the final rate is 17%,the per-centage reduction in interest rate is 18−17 /18=5 56%.rate decreases only if the loan request receives full greater lender interest results in greater reduc-of the interest rate.Third,loan performance is the payment status of the loan two years after its origination.We further classify the types of identity claims made by prospective borrowers.Borrowers in our sample employed six identity claims in their narratives:trustworthy,economic hardship,hardworking,successful,moral,and religious.In Table 1,we provide definitions and illustrative examples of each identity claim.Borrowers provided an average of 1.53 SD =1 14 identity claims in their narratives.RESEARCH HYPOTHESESWho Is Likely to Provide More Identity Claims in Their Narratives?Narratives,when viewed as vehicles for identity work,provide opportunities for people to manage the impres-sions that others hold of them.Impression management the-ory posits that people want to create and maintain specific identities (Leary and Kowalski 1990).Narratives provide an avenue for impression management;through discourse,people can shape situations and construct identities that are designed specifically to obtain a desired outcome (Schlenker and Weigold 1992).Some scholars argue that people use narratives strategically to establish,maintain,or protect their desired identities (Rosenfeld,Giacalone,and Riordan 1995).However,the use of impression manage-ment need not automatically signal outright lying;people may select from a repertoire of self-images they genuinely believe to be true (Leary and Kowalski 1990).Nevertheless,strategic use of impression management means that,at a minimum,people select representations of their self-image that are most likely to garner support.In economic exchanges involving repeated transactions,each party receives feedback from exchange partners thateither validates or disputes the credibility of their self-constructions (Leary and Kowalski 1990),so they can determine if an identity claim has been granted.Prior transactions also offer useful information through feedback ratings and other mechanisms that convey and archive rep-utations (Weiss,Lurie,and MacInnis 2008).However,in one-time economic exchanges,such feedback is not avail-able.Instead,narrators have a single opportunity to present a convincing public view of the self,and receivers of the information have only one presentation to deem the presen-ter as credible or not.We hypothesize that in these conditions,borrowers are strategic in their identity claims.Borrowers with satisfac-tory objective characteristics are less likely to construct identity claims to receive funding;they feel their case stands firmly on its objective merits alone.In contrast,borrowers with unsatisfactory objective characteristics may view narratives as an opportunity to influence the attribu-tions that lenders make,because in narratives,they can counter past mistakes and difficult circumstances.In this scenario,borrowers make identity claims that offset the attributions made by lenders about the borrower being fundamentally not a creditworthy person.These disposi-tional attributions are often based on visible characteristics (Gilbert and Malone 1995).The most relevant objective characteristic of borrowers is the credit grade assigned by Prosper,derived from the borrower’s personal credit history (Herzenstein,Dholakia,and Andrews 2011).With more than one identity claim,borrowers can present a more com-plex,positive self to counteract negative objective informa-tion,such as a low credit grade.Thus:H 1:The lower the borrower’s credit grade,the greater isthe number of identities claimed by the borrower in the narrative.Role of Narratives in Peer-to-Peer Lending Decisions S141Impact of the Number of Identity Claims onLenders’DecisionAlthough economists often predict that unverifiable information does not matter(e.g.,Farrell and Rabin1996), we suggest that the number of identity claims in a bor-rower’s narrative play a role in lenders’decision making, for at least two reasons.First,borrower narratives with too few identities may fail to resolve questions about the borrower’s disposition.If a borrower fails to provide suf-ficient diagnostic information for lenders to make attri-butions about the borrower(Cramton2001),lenders may suspect that the borrower lacks sufficient positive or dis-tinctive information or is withholding or hiding germane information.Second,the limited diagnostic information provided by fewer identity claims limits a decision maker’s ability to resolve outcome uncertainties.Research on perceived risk supports this reasoning;decision makers gather informa-tion as a risk-reduction strategy and tend to be risk averse in the absence of sufficient information about the decision (e.g.,Cox and Rich1964).In the P2P lending arena,the loan request and evaluation process unfold online with-out any physical interaction between the parties.Further-more,on Prosper,borrowers are anonymous(real names and addresses are never revealed).This lack of seemingly relevant information is especially salient,because many decision makers view unmediated online environments as ripe for deception(Caspi and Gorsky2006).To the extent that the identity claims presented in a narrative reduce uncertainty about a borrower,lenders should be more likely to view the listing favorably,increase loan funding,and decrease thefinal interest rate.Therefore,the number of identity claims in a borrower’s narrative may serve as a heuristic for assessing the borrower’s loan application and lead to greater interest in the listing.Although we suggest that the number of identities bor-rowers claim result in favorable lending decisions,we also argue that these identity claims may persuade lenders erroneously,such that lenders fund loans with a lower likelihood of repayment.Borrowers can use elaborate multiple-identity narratives to craft“not-quite-true”stories and make promises they mightfind difficult to keep.More generally,a greater number of identity claims suggests that borrowers are being more strategic and positioning them-selves in a manner they believe is likely to resonate with lenders,as opposed to presenting a true self.Therefore,we posit that,consciously or not,borrowers who construct sev-eral identities may have more difficulty fulfilling their obli-gations and be more likely to fall behind on or stop loan repayments altogether.Thus,despite the high stakes of the decision,lenders swayed by multiple identities are more likely to fall prey to borrowers that underperform or fail (Goffman1959).H2:Controlling for objective,verifiable information,the more identities borrowers claim in their loan requests,the morelikely lenders are to(a)fund the loan and(b)reduce itsinterest rate,but then(c)the lower is the likelihood of itsrepayment.Role of the Content of Identity Claims onLender Decision Making and Loan PerformanceWe also examine the extent to which select identities affect lenders’decision making and the longer-term per-formance of loans.With a limited theoretical basis for determining the types of identities most likely to influ-ence lenders’decision making,this part of our study is exploratory.Research on trust offers a promising starting point(Mayer,Davis,and Schoorman1995),because it sug-gests that identities may reduce dispositional uncertainty and favorably influence lenders.Trust is a crucial element for the consummation of an economic exchange(Arrow 1974).Scholars theorize that trust involves three compo-nents:integrity(borrowers adhere to principles that lenders accept),ability(borrowers possess the skills necessary to meet obligations),and benevolence(borrowers have some attachment to lenders and are inclined to do good)(Mayer, Davis,and Schoorman1995).We theorize that trustworthy,religious,and moral iden-tities increase perceptions of integrity because they lead lenders to believe that borrowers ascribe to the lender-endorsed principle of fulfilling obligations,either directly (trustworthy)or indirectly by adhering to a philosophy (religious or moral).Specifically,a moral identity tells potential lenders that the person has“a self-conception organized around a set of moral traits”(Aquino et al.2009, p.1424),which should increase perceptions of integrity.A religious identity signals a set of role expectations to which a person is likely to adhere,and though religions vary in the content of these expectations(Weaver and Agle 2002),many of them include principles oriented against lying or stealing and toward honoring contractual agree-ments.A hardworking identity should increase perceptions of integrity,because hardworking people are determined and dependable,which often makes them problem solvers (Witt et al.2002),meaning that they will do their best to meet their obligations,a disposition likely to resonate with lenders.We also reason that the religious and moral identities invoke in lenders a sense of benevolence,which is a foun-dational principle of many religions and moral philoso-phies.Similarly,the economic hardship identity may invoke benevolence,because the borrower exhibits forthrightness about his or her past mistakes and thus suggests to lenders that the borrower is trying to create a meaningful relation-ship based on transparency.We theorize that an identity claim of success can increase perceptions of ability and the belief that the narrator is capable of fulfilling promises(Butler1991).Lenders are more likely to lend money to a borrower if they perceive that the person is capable of on-time repayment(Newall and Swan2000).A successful identity likely describes the past or present,but it also can serve as an indication of a probable future(i.e.,the borrower will continue to be successful),which helps“fill in the blanks”about the bor-rower in a positive way.In contrast,economic hardship likely constructs the borrower as someone who has had a setback,which ultimately undermines perceptions of ability and thus negatively affects lenders’decisions.We have offered some preliminary theory in support of these specific relationships between identity content and loan funding/interest rate reductions,but this examinationS142JOURNAL OF MARKETING RESEARCH,SPECIAL ISSUE2011remains exploratory,so we pose these relationships as exploratory research questions(ERQ):ERQ1:Which types of identity claims influence lending deci-sions,as indicated by(a)an increase in loan fundingand(b)a decrease in thefinal interest rate?We also explore the impact of the content of identity claims on loan performance.We envision two potential sce-narios.In thefirst,identities are diagnostic of the borrower or serve as self-fulfilling prophecies.Examining the ability aspect of trustworthiness,we anticipate a negative relation between an economic hardship identity and loan perfor-mance(borrowers validate their claim of setbacks)but a positive relation between a successful identity and loan per-formance(borrowers prove their claim of past success). Moreover,we expect the four integrity-related identities—trustworthy,hardworking,moral,and religious—to indicate better loan performance.After a self-presentation as having integrity,the borrower probably has a strong psychological desire for consistency between the narrative and his or her actions(Cialdini and Trost1998).That is,in their narra-tives,borrowers may make an active,voluntary,and public commitment that psychologically binds them to a partic-ular set of beliefs and subsequent behaviors(Berger and Heath2007).Because these four identities speak to funda-mental self-beliefs versus predicted outcomes(e.g.,success or hardship),they can strongly motivate borrowers to live up to their claims.Thus these identities,regardless of their accuracy,can become true and predict the performance of the lending decision.In the other scenario,however,identities improve the lender’s impression of the borrower,thereby allowing bor-rowers to exert control over the provided impressions (Goffman1959).Borrowers(or narrators,more generally) construct positive impressions and may misrepresent them-selves and send signals that may not be objectively war-ranted.Despite the belief that self-constructing identities are helpful for a lending decision,they actually may have no impact or even be harmful to lenders.These mixed pos-sibilities lead to another exploratory research question: ERQ2:How are the content of identity claims and loan perfor-mance related?STUDYDataOur data set consists of1,493loan listings posted by borrowers on Prosper in June2006and June2007.We extracted this data set using a stratified random sampling ing a web crawler,we extracted all loan listings posted in June2006and June2007(approximately5,400 and12,500listings,respectively).A significant percentage of borrowers on Prosper have very poor credit histories, and most loan requests do not receive funding.To avoid overweighting high-risk borrowers and unfunded loans,we sampled an equal number of loan requests from each credit grade.To do so,wefirst separated funded loan requests from unfunded ones,then divided each group by the seven credit grades assigned by Prosper.We also eliminated all loan requests without any narrative text,for three reasons. First,including loan requests without narratives could con-found the borrower’s choice to write something other than narratives in the open text box with the choice to write nothing at all.Second,the vast majority of listings lack-ing a narrative do not receive funding.Third,loan requests without text represent only9%of all loans posted in June 2006and4%of those posted in June2007.We nevertheless used the“no text”loans in our robustness check.We randomly sampled posts from the14subgroups (2funding status×7credit grades).In2006,we sampled 40listings from each subgroup(until data were exhausted) to obtain513listings;in2007,we sampled70listings from each subgroup to obtain980listings,for a total of 1,493listings.Each listing includes the borrower’s credit grade,requested loan amount,maximum interest rate,loan funding,final interest rate of funded loans,payback sta-tus of funded loans after two years,and open-ended text data.Before combining the data from2006and2007,we tested for a year effect but found none,which supports their combination.Dependent VariablesThefirst dependent variable,loan funding,ranges from 0%to905%in our data set,but requiring an equal inclu-sion of all credit ratings skews these statistics.The mean percentage funded(including all listings)is105.74%(SD= 129 2)and that for funded listings is205.45%(SD=119 6). Because it was skewed,we log-transformed loan fund-ing as follows:Ln(percent funded+1).The second depen-dent variable,percentage reduction in thefinal interest rate, ranges from0%to56%in our data set.The mean per-centage reduction in interest rate for all listings is6.4% (SD=10 7)and for funded listings is11.88%(SD=12 75). Because the distribution is skewed,we log-transformed it (we provide the distributionfigures in the Web Appendix, /jmrnov11).The third dependent variable is loan performance,mea-sured two years after loan funding.For each funded loan in our data set,we obtained data about whether the loan was paid ahead of schedule and in full(31.1%of funded list-ings),was current and paid as scheduled(40.5%),involved payments between one and four months late(7.1%),or had defaulted(21.3%).This dependent variable may appear ordered,but the likelihood ratio tests reveal that a multino-mial logit model fares better than an ordered logit model for analyzing these data(for both the number and content of identities).Thus,in the following analysis,we employ a multinomial logit model.Independent VariablesWe read approximately one-third of all narratives and developed our inductively derived list of six identity claims (Miles and Huberman1994):trustworthy,economic hard-ship,hardworking,successful,moral,and religious,as we define in Table1.Two research assistants examined the same data and determined these six identities were exhaustive.Next,five additional pairs of research assistants (10total)coded the entire data set.We coded each iden-tity as a dichotomous variable that receives the value of1 if the identity claim was present in a borrower’s narrative and0if otherwise.A pair of research assistants read each listing in the data set,independently atfirst,then discussed them to determine the unified code for each listing.Accord-ing to20randomly sampled listings from our data set,used。

EVOLUTION OF INDIAN BIOTECH & FINANCING IMPLICATIONS

EVOLUTION OF INDIAN BIOTECH & FINANCING IMPLICATIONS

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FINANCING ENVIRONMENT SUPPORTS THESE CLUSTERS
VC funding •‘05: $1,215 M •‘06: $1,176 M •‘07 H1: $603 M Companies funded •‘05: 77 •‘06: 97 •‘07 H1: 46
San Diego
VC funding •‘05: $628 M •‘06: $845 M •‘07 H1: $451 M Companies funded •‘05: 57 •‘06: 71 •‘07 H1: 42 Research alliances •‘96-’01: $3.9 B
Proprietary analysis
Background experience
Verbiage
Fund size Duration of investment Expected IRR
4 years
7 years
25-40%
Closer to 40%
Proprietary analysis
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IMPLICATIONS FOR INDIAN BIOTECHS…
On average… Organizational focus Roots Organizational physiology Partnerships • Generics • Services • Trading • Manufacturing • Follow the leader • Command and control • Partner for commercialization only • Arms-length relationships; short-lived Generics/CRAMS companies spending 3-6% of sales Top leadership – even though few have entrepreneurial track record • Top guy has worked/studied abroad • Major turnover in 2nd level talent What’s required Product innovation • Nerds in a garage • University licensing • Spinoffs • Multi-focal teams • Focused entropy • Extensive alliances • Flawless management of partnerships • Venture funding • 15% of sales for commercial organizations • Scientific focus/program • Leadership with track record • N and N-1 are very stable • Share risk/reward

《不择手段背单词》完整版(O-R)

《不择手段背单词》完整版(O-R)

4924,"oafish","[`EJfIF]adj 痴呆的;愚蠢的【记】读:o哦,a fish,哦,这儿有一条鱼-很傻的感觉【区】oak(n 橡树);oar(n 船桨);oatmeal=oat(n 燕麦片)【反】urbanity(n 有礼貌;文雅)-oafishness"4925,"oasis","[EJ5eIsIs]n 沙漠中的绿洲【记】o哦,as好像,is是:哦,好像是绿洲(一般在沙漠中见到绿洲都有一点儿不相信自己的眼睛,所以是“好像”)【类】glade:wood=oasis:desert=archipelago:ocean林间空地在树木中=绿洲在沙漠中=群岛在海洋中"4926,"obdurate","[5RbdjJrIt; (?@) 5BbdErIt]adj 固执的;不知悔意的=hardhearted=intractable【记】ob不,dur=endure 忍耐,ate一不能忍耐变化一固执的【类】firmness:obdurate=carefulness:meticulous特别坚定是顽固的=特别小心是十分小心的energetic:frenetic=firm:obdurate=frugal:penurious特积极的是狂热的=特坚定的是顽固的=特节俭的是吝啬的penitent:obdurate=skeptic:credulous悔过者不是顽固的=怀疑者不是轻信的obdurate:move=? 顽固的不会动摇=?【反】toward(adj 温顺的)"4927,"obedient","[EJ5bi:dIEnt]adj (对上级命令、指示或指令)服从的,顺从的【记】源于:obey(v 服从)【反】contumacious(adj 不听令的);impertinent(adj 鲁莽无礼的);imperious(adj 专横的);impudent(adj 放肆无礼的);imperial(adj 皇帝的)"4928,"obeisance","[EJ5beIsEns]n (表示尊重或敬意的)鞠躬,敬礼【类】obeisance:reverence=embrace:affection 鞠躬表示敬意=拥抱表示友情"4929,"obese","[EJ5bi:s]adj 极其肥胖的【记】读:我必死,因为太太太胖了"4930,"obfuscate","[5RbfQskeIt]v 使困惑(使得难于理解)【记】ob,fusc=fuse导火索,ate吃:在吃的上面插导火索-使困惑【类】headstrong:willfulness=obfuscate:confusing顽固的:任性=使困惑:胡涂的(词性不符)cowardice:intimidate=perplexed:obfuscate懦弱是因为被胁迫=困惑的是因为被使模糊【反】elucidate(v 阐明);illuminate(v 照明;阐明);explain clearly(清楚解释);clarify(v 澄清);"4931,"obfuscation","n 困惑【类】equivocation:truth=euphemis m:offense=obfuscation:clarity真理不含糊=冒犯不委婉=清晰不困惑rationalization:plausible=obfuscation:indiscernible『equivocation:definite』合理化不是似是而非的=困惑不是难以识别的『模棱两可不是确定的』【反】lucidity(n 明朗)"4932,"obituary","[E5bItjJErI; (?@) E5bItFJerI]n 讣闻(死后发表的附有死者简要传记)【记】ob离开,it他,uary:他离开我们后写的东西-讣告【类】roster:staff=obituary:death花名册记录职员=讣告记录死亡"4933,"oblation","[E5bleIF(E)n]n 供品,祭品(向神供奉,为了敬神或感恩)【记】读:我不累神-我不累的为神提供祭品"4934,"obligatory","[E5blI^EtErI]adj 强制性的;义不容辞的【记】源于:oblige(v 迫使;施恩);obligation(n 义务)【类】elected:obliged=? 选举出的:强迫=?【反】discretionary(adj 自由决定的);selective(adj 选择性的);elective(adj 选任的);oblige(v 迫使;施恩;帮忙)-discommode(v 使不方便)"4935,"obliging","[E5blaIdVIN]adj 热心助人的=accommodating【记】源于:oblige(v 迫使;施恩;帮忙)【类】visionary:idealistic=officious:obliging幻想的:理想主义的=过分插手的:热心的(褒贬)"4936,"oblique","[E5bli:k]adj 斜的;不坦率的【记】读:我不立que一不是站着-斜的【反】direct(adj 径直的)"4937,"obliterate","[E5blItEreIt]v 擦掉(字迹);切除(肢体)【记】ob去掉,liter字,ate一擦掉(文字)【类】inspire:infuse =obliterate:remove=accomodate:supply=convey:conduct激励=除掉=提供=运输(同义)inter:burial=obliterate:removal=saturated:wet埋葬=除掉(动名词同义)=湿的(词性不符)ineffable:description=irradicable:obliterate不能说的无法描述=不能根除的无法删除【反】inexpurgate(v 无法除去)"4938,"oblivious","[E5blIvIEs]adj 遗忘的;疏忽的【记】读:我不理vious,我不理你了,我要把你忘了。

Explicating dynamic capabilities the nature and microfoundations

Explicating dynamic capabilities the nature and microfoundations

Strategic Management JournalStrat.Mgmt.J.(2007)Published online in Wiley InterScience ()DOI:10.1002/smj.640Received 16February 2004;Final revision received 20June 2007EXPLICATING DYNAMIC CAPABILITIES:THE NATURE AND MICROFOUNDATIONS OF (SUSTAINABLE)ENTERPRISE PERFORMANCEDAVID J.TEECE*Institute of Management,Innovation and Organization,Haas School of Business,University of California,Berkeley,California,U.S.A.This paper draws on the social and behavioral sciences in an endeavor to specify the nature and microfoundations of the capabilities necessary to sustain superior enterprise performance in an open economy with rapid innovation and globally dispersed sources of invention,innova-tion,and manufacturingcapability.Dynamic capabilities enable business enterprises to create,deploy,and protect the intangible assets that support superior long-run business performance.The microfoundations of dynamic capabilities—the distinct skills,processes,procedures,orga-nizational structures,decision rules,and disciplines—which undergird enterprise-level sensing,seizing,and reconfiguring capacities are difficult to develop and deploy.Enterprises with strong dynamic capabilities are intensely entrepreneurial.They not only adapt to business ecosystems,but also shape them through innovation and through collaboration with other enterprises,enti-ties,and institutions.The framework advanced can help scholars understand the foundations of long-run enterprise success while helping managers delineate relevant strategic considerations and the priorities they must adopt to enhance enterprise performance and escape the zero profit tendency associated with operating in markets open to global competition.Copyright 2007John Wiley &Sons,Ltd.INTRODUCTIONRecent scholarship stresses that business enter-prises consist of portfolios of idiosyncratic and difficult-to-trade assets and competencies (’re-sources’).1Within this framework,competitive advantage can flow at a point in time from the ownership of scarce but relevant and difficult-to-imitate assets,especially know-how.However,inKeywords:cospecialization;intangible assets;innovation;business ecosystems;entrepreneurship;managerial capi-talism;global competitiveness*Correspondence to:David J.Teece,F402Haas School of Business #1930,University of California,Berkeley,California 94720-1930,U.S.A.E-mail:teece@ 1The reference here is to the resource-based theory of the enterprise advanced by Rumelt (1984),Wernerfelt (1984),Amit and Schoemaker (1993),and others.Some of my earlier work (Teece,1980,1982)was also in this vein.fast-moving business environments open to global competition,and characterized by dispersion in the geographical and organizational sources of inno-vation and manufacturing,sustainable advantage requires more than the ownership of difficult-to-replicate (knowledge)assets.It also requires unique and difficult-to-replicate dynamic capabili-ties.These capabilities can be harnessed to con-tinuously create,extend,upgrade,protect,and keep relevant the enterprise’s unique asset base.For analytical purposes,dynamic capabilities can be disaggregated into the capacity (1)to sense and shape opportunities and threats,(2)to seize opportunities,and (3)to maintain competitiveness through enhancing,combining,protecting,and,when necessary,reconfiguring the business enter-prise’s intangible and tangible assets.Dynamic capabilities include difficult-to-replicate enterpriseCopyright 2007John Wiley &Sons,Ltd.D.J.Teececapabilities required to adapt to changing cus-tomer and technological opportunities.They also embrace the enterprise’s capacity to shape the ecosystem it occupies,develop new products and processes,and design and implement viable busi-ness models.It is hypothesized that excellence in these‘orchestration’2capacities undergirds an enterprise’s capacity to successfully innovate and capture sufficient value to deliver superior long-termfinancial performance.The thesis advanced is that while the long-run performance of the enter-prise is determined in some measure by how the (external)business environment rewards its her-itage,the development and exercise of(internal) dynamic capabilities lies at the core of enterprise success(and failure).This paperfirst describes the nature of dynamic capabilities,and then explicates their microfoundations.The ambition of the dynamic capabilities frame-work is nothing less than to explain the sources of enterprise-level competitive advantage over time, and provide guidance to managers for avoiding the zero profit condition that results when homoge-neousfirms compete in perfectly competitive mar-kets.A framework,like a model,abstracts from reality.It endeavors to identify classes of relevant variables and their interrelationships.A framework is less rigorous than a model as it is sometimes agnostic about the particular form of the theoreti-cal relationships that may exist.Early statements of the dynamic capabilities framework can be found in Teece,Pisano,and Shuen(1990a,1990b,1997) and Teece and Pisano(1994).An extensive lit-erature on dynamic capabilities now exists(e.g., Helfat et al.,2007)that can be organized and inte-grated into the general framework offered here. As indicated,the possession of dynamic capabil-ities is especially relevant to multinational enter-prise performance in business environments that display certain characteristics.Thefirst is that the environment is open to international commerce and fully exposed to the opportunities and threats asso-ciated with rapid technological change.The sec-ond is that technical change itself is systemic in 2The management functions identified are analogous to that of an orchestra conductor,although in the business context the ‘instruments’(assets)are themselves constantly being created, renovated,and/or replaced.Moreover,completely new instru-ments appear with some frequency,and old ones need to be abandoned.Whileflexibility is certainly an element of orches-tration,the latter concept implies much more.that multiple inventions must be combined to cre-ate products and/or services that address customer needs.The third is that there are well-developed global markets for the exchange of(component) goods and services;and the fourth is that the busi-ness environment is characterized by poorly devel-oped markets in which to exchange technological and managerial know-how.These characteristics can be found in large sectors of the global econ-omy and especially in high-technology sectors.In such sectors,the foundations of enterprise success today depend very little on the enterprise’s abil-ity to engage in(textbook)optimization against known constraints,or capturing scale economies in production.Rather,enterprise success depends upon the discovery and development of opportuni-ties;the effective combination of internally gener-ated and externally generated inventions;efficient and effective technology transfer inside the enter-prise and between and amongst enterprises;the protection of intellectual property;the upgrading of‘best practice’business processes;the inven-tion of new business models;making unbiased decisions;and achieving protection against imita-tion and other forms of replication by rivals.It also involves shaping new‘rules of the game’in the global marketplace.The traditional elements of business success—maintaining incentive align-ment,owning tangible assets,controlling costs, maintaining quality,‘optimizing’inventories—are necessary but they are unlikely to be sufficient for sustained superior enterprise performance. Executives seem to recognize new challenges in today’s globally competitive environments and understand how technological innovation is nec-essary but not sufficient for fley, CEO of Proctor&Gamble,notes that‘the name of the game is innovation.We work really hard to try to turn innovation into a strategy and a process ...‘.3Sam Pamisano,CEO of IBM,remarks that ‘innovation is about much more than new prod-ucts.It is about reinventing business processes and building entirely new markets that meet untapped customer demand.’4Put differently,there is an emerging recognition by managers themselves that the foundations of enterprise success transcend simply being productive at R&D,achieving new product introductions,adopting best practice,and delivering quality products and services.Not only 3Fortune,December11,2006:4.4Business Week,April24,2004:64.Explicating Dynamic Capabilities:Nature and Microfoundationsmust the innovating enterprise spend heavily on R&D and assiduously develop and protect its intel-lectual property;it must also generate and imple-ment the complementary organizational and man-agerial innovations needed to achieve and sustain competitiveness.As indicated,not all enterprise-level responses to opportunities and threats are manifestations of dynamic capabilities.As Sidney Winter(2003: 991)notes,‘ad hoc problem solving’isn’t neces-sarily a capability.Nor is the adoption of a well-understood and replicable‘best’practice likely to constitute a dynamic capability.Implementing best practice may help an enterprise become or remain viable,but best practices that are already widely adopted cannot by themselves in a competitive market situation enable an enterprise to earn more than its cost of capital,or outperform its competi-tors.Likewise,invention and innovation by them-selves are insufficient to generate success(Teece, 1986).Two yardsticks can be proposed for calibrating capabilities:‘technical’fitness and‘evolutionary’fitness(Helfat et al.,2007).Technicalfitness is defined by how effectively a capability performs its function,regardless of how well the capability enables afirm to make a living.Evolutionary or externalfitness refers to how well the capability enables afirm to make a living.Evolutionaryfit-ness references the selection environment.Helfat et al.(2007)further note that both technical and evolutionaryfitness range from zero to some pos-itive value.These yardsticks are consistent with the discussion here.Dynamic capabilities assist in achieving evolutionaryfitness,in part by helping to shape the environment.The element of dynamic capabilities that involves shaping(and not just adapting to)the environment is entrepreneurial in nature.Arguably,entrepreneurialfitness ought to have equal standing with evolutionaryfitness. Dynamic capabilities have no doubt been rele-vant to achieving competitive advantage for some time.However,their importance is now ampli-fied because the global economy has become more open and the sources of invention,innovation,and manufacturing are more diverse geographically and organizationally(Teece,2000),and multiple inventions must be combined to achieve market-place success(Somaya and Teece,2007).Achiev-ing evolutionaryfitness is harder today than it was before the millennium.Moreover,regulatory and institutional structures must often be reshaped for new markets to emerge;and as discussed later,the ubiquity of‘platforms’must now be recognized (Evans,Hagiu,and Schmalensee,2006).While the development and astute management of intangible assets/intellectual capital is increas-ingly recognized as central to sustained enter-prise competitiveness,the understanding of why and how intangibles are now so critical still remains opaque and is not addressed by orthodox frameworks.What is needed is a new framework for business and economic analysis.As former U.S.Federal Reserve Chairman Alan Greenspan remarked,‘we must begin the important work of developing a framework capable of analyzing the growth of an economy increasingly dominated by conceptual products.’5The dynamic capabilities approach developed here endeavors to be respon-sive to this challenge at the enterprise level.In an earlier treatment(Teece et al.,1997:530) it was noted that‘we have merely sketched an out-line for a dynamic capabilities approach.’In what follows,the nature of various classes of dynamic capabilities is identified,and an effort is made to separate the microfoundations of dynamic capa-bilities from the capability itself.Put differently, important distinctions are made between the orga-nizational and managerial processes,procedures, systems,and structures that undergird each class of capability,and the capability itself.One should note that the identification of the microfounda-tions of dynamic capabilities must be necessarily incomplete,inchoate,and somewhat opaque and/or their implementation must be rather difficult.Oth-erwise sustainable competitive advantage would erode with the effective communication and appli-cation of dynamic capability concepts.Of course,the existence of processes,proce-dures,systems,and structures already ubiquitously adopted by competitors does not imply that these have not in the past been the source of competitive advantage,or might not still be a source of compet-itive advantage in certain contexts.For example, studies of the diffusion of organizational innova-tions(e.g.,Armour and Teece,1978;Teece,1980) 5Chairman Alan Greenspan also noted recently,‘over the past half century,the increase in the value of raw materials has accounted for only a fraction of the overall growth of U.S.gross domestic product(GDP).The rest of that growth reflects the embodiment of ideas in products and services that consumers value.This shift of emphasis from physical materials to ideas as the core of value creation appears to have accelerated in recent decades.’(Remarks of Alan Greenspan,Stanford Institute for Economic Policy Research,2004.)D.J.Teeceindicate that diffusion is by no means instanta-neous,and that profits can persist for many years before being competed away.Decade-long adop-tion cycles for new business structures and pro-cedures(e.g.,performance measurement systems) are not uncommon.Uncertain imitability(Lippman and Rumelt,1982)may also serve to slow the dif-fusion process and support persistent differential performance.Fortunately,the existing literature on strategy, innovation,and organization and the new literature on dynamic capabilities have identified a panoply of processes and routines that can be recognized as providing certain microfoundations for dynamic capabilities.For instance,Eisenhardt and Martin (2000)identify cross-functional R&D teams,new product development routines,quality control rou-tines,and technology transfer and/or knowledge transfer routines,and certain performance mea-surement systems as important elements(micro-foundations)of dynamic capabilities.The effort here is not designed to be comprehensive,but to integrate the strategy and innovation literature and provide an umbrella framework that highlights the most critical capabilities management needs to sus-tain the evolutionary and entrepreneurialfitness of the business enterprise.SENSING(AND SHAPING) OPPORTUNITIES AND THREATS Nature of the capabilityIn fast-paced,globally competitive environments, consumer needs,technological opportunities,and competitor activity are constantly in a state offlux. Opportunities open up for both newcomers and incumbents,putting the profit streams of incum-bent enterprises at risk.As discussed in Teece et al.(1997),some emerging marketplace trajecto-ries are easily recognized.In microelectronics this might include miniaturization,greater chip density, and compression and digitization in information and communication technology.However,most emerging trajectories are hard to discern.Sensing (and shaping)new opportunities is very much a scanning,creation,learning,and interpretive activ-ity.Investment in research and related activities is usually a necessary complement to this activity. Opportunities get detected by the enterprise because of two classes of factors.First,as stressed by Kirzner(1973),entrepreneurs can have differ-ential access to existing information.Second,new information and new knowledge(exogenous or endogenous)can create opportunities,as empha-sized by Schumpeter(1934).Kirzner stressed how the entrepreneurial function recognizes any dise-quilibrium and takes advantage of it.The Kirzner-ian view is that entrepreneurship is the mechanism by which the economy moves back toward equi-librium.Schumpeter,on the other hand,stressed upsetting the equilibrium.As Baumol(2006:4) notes,‘the job of Schumpeter’s entrepreneur is to destroy all equilibria,while Kirzner’s works to restore them.This is the mechanism under-lying continuous industrial evolution and revolu-tion.’Equilibrium is rarely if ever achieved(Shane, 2003).Both forces are relevant in today’s econ-omy.To identify and shape opportunities,enterprises must constantly scan,search,and explore across technologies and markets,both‘local’and‘dis-tant’(March and Simon,1958;Nelson and Winter, 1982).This activity not only involves investment in research activity and the probing and reprob-ing of customer needs and technological possibili-ties;it also involves understanding latent demand, the structural evolution of industries and mar-kets,and likely supplier and competitor responses. To the extent that business enterprises can open up technological opportunities(through engaging in R&D and through tapping into the research output of others)while simultaneously learning about customer needs,they have a broad menu of commercialization opportunities.Overcoming a narrow search horizon is extremely difficult and costly for management teams tied to established problem-solving competences.Henderson(1994) notes that General Motors(GM),IBM,and Dig-ital Equipment Corporation(DEC)encountered difficulties because they became prisoners of the deeply ingrained assumptions,informationfilters, and problem-solving strategies that made up their world views,turning the solutions that once made them great into strategic straitjackets.When opportunities arefirst glimpsed,entrepre-neurs and managers mustfigure out how to inter-pret new events and developments,which tech-nologies to pursue,and which market segments to target.They must assess how technologies will evolve and how and when competitors,suppli-ers,and customers will petitors may or may not see the opportunity,and even if theyExplicating Dynamic Capabilities:Nature and Microfoundationsdo they may calibrate it differently.Their actions, along with those of customers,suppliers,standard-setting bodies,and governments,can also change the nature of the opportunity and the manner in which competition will unfold.There are also constraints on the rules by which competitive forces will play out.These constraints are imposed by regulators,standard-setting bod-ies,laws,social mores,and business ethics.The shape of the‘rules of the game’is thus the result of co-evolution and complex interaction between what might be thought of as(business) ecosystem participants.Because of uncertainty, entrepreneurs/managers must make informed con-jectures about the path ahead.These conjectures become working hypotheses that can be updated as evidence emerges.Once a new evolutionary path becomes apparent,quick action is needed. MicrofoundationsThe literature on entrepreneurship emphasizes that opportunity discovery and creation can originate from the cognitive and creative(’right brain’) capacities of individual(s).However,discovery can also be grounded in organizational processes,such as research and development activity.The ability to create and/or sense opportunities is clearly not uniformly distributed amongst individuals or enter-prises.Opportunity creation and/or discovery by individuals require both access to information and the ability to recognize,sense,and shape devel-opments.The ability to recognize opportunities depends in part on the individual’s capabilities and extant knowledge(or the knowledge and learning capacities of the organization to which the indi-vidual belongs)particularly about user needs in relationship to existing as well as novel solutions. This requires specific knowledge,creative activity, and the ability to understand user/customer deci-sion making,and practical wisdom(Nonaka and Toyama,2007).It involves interpreting available information in whatever form it appears—a chart, a picture,a conversation at a trade show,news of scientific and technological breakthroughs,or the angst expressed by a frustrated customer.One must accumulate and thenfilter information from profes-sional and social contacts to create a conjecture or a hypothesis about the likely evolution of technolo-gies,customer needs,and marketplace responses. This task involves scanning and monitoring inter-nal and external technological developments and assessing customer needs,expressed and latent. It involves learning,interpretation,and creative activity.While certain individuals in the enterprise may have the necessary cognitive and creative skills, the more desirable approach is to embed scan-ning,interpretative,and creative processes inside the enterprise itself.The enterprise will be vulner-able if the sensing,creative,and learning functions are left to the cognitive traits of a few individuals.6 Organizational processes can be put in place inside the enterprise to garner new technical information, tap developments in exogenous science,monitor customer needs and competitor activity,and shape new products and processes r-mation must befiltered,and mustflow to those capable of making sense of it.Internal argument and discussion about changing market and tech-nological reality can be both inductive and deduc-tive.Hypothesis development,hypothesis‘testing,’and synthesis about the meaning of information obtained via search are critical functions,and must be performed by the top management team.The rigorous assembly of data,facts,and anecdotes can help test beliefs.Once a synthesis of the evidence is achieved,recurrent synthesis and updating can be embedded in business processes designed by middle management and/or the planning unit in the business organization(Casson,1997).If enter-prises fail to engage in such activities,they won’t be able to assess market and technological devel-opments and spot opportunities.As a consequence, they will likely miss opportunities visible to others. As noted in Teece et al.(1997),more decen-tralized organizations with greater local autonomy are less likely to be blindsided by market and technological developments.Because of the prob-lem of information decay as information moves up(and down)a hierarchy,businesses must devise mechanisms and procedures to keep management informed.Bill Hewlett and David Packard devel-oped‘management by walking about’(Packard, 1995)as a mechanism to prevent top management at Hewlett-Packard from becoming isolated from 6In a limited sense,that is about decision making under uncer-tainty.As Knight observes,with uncertainty there is‘a necessity to act upon opinion rather than knowledge’(Knight,1921:268). The problem is not just about knowledge asymmetries and incen-tive problems as Alchian and Demsetz(1972)seem to suggest. Rather,it involvesfiltering and interpreting information about evolving technologies and marketplaces.D.J.Teecewhat was going on at lower levels in the enter-prise,and outside the enterprise as well.In other organizations(e.g.,professional services)the man-agement ranks can befilled by leading profession-als who remain involved with professional work. This protects them from the hazards of managerial isolation.The search activities that are relevant to‘sens-ing’include information about what’s going on in the business ecosystem.With respect to technolo-gies,R&D activity can itself be thought of as a form of‘search’for new products and processes. However,R&D is too often usually a manifesta-tion of‘local’search.‘Local’search is only one component of relevant search.In fast-paced envi-ronments,with a large percentage of new prod-uct introductions coming from external sources, search/exploration activity should not just be local. Enterprises must search the core as well as to the periphery of their business ecosystem.Search must embrace potential collaborators—customers, suppliers,complementors—that are active in inno-vative activity.Customers are sometimes amongst thefirst to perceive the potential for applying new technol-ogy.Visionary members of customer organizations are often able to anticipate the potential for new technology and possibly even begin rudimentary development activities.Moreover,if the suppli-ers of new technology do not succeed in properly understanding user/customer needs,it is unlikely that new products they might develop will be suc-cessful.Indeed,one of the most consistentfindings from empirical research is that the probability that an innovation will be successful commercially is highly correlated with the developers’understand-ing of user/customer needs(Freeman,1974).Elec-tronic computing and the Internet itself can rightly be viewed as having a significant component of user-led innovations.Business enterprises that are alert and sense the opportunity are often able to leverage customer-led efforts into new products and services,as the users themselves are frequently ill prepared to carry initial prototypes further for-ward.Suppliers can also be drivers of innovation important in thefinal product.Innovation in micro-processor and DRAMs is a classic case.This upstream or‘component’innovation has impacted competition and competitive outcomes in personal computers,cellular telephony,and consumer elec-tronics more generally.Failure to‘design in’new technology/components in a timely fashion will lend to failure;conversely,success can some-times be achieved by continuous rapid‘design in.’Indeed,continuous and rapid design around new technology/components developed elsewhere can itself be a source of durable competitive advan-tage.Put differently,with rapid innovation by com-ponent suppliers,downstream competitive success canflow from the ability of enterprises to continu-ously tap into such(external)innovation ahead of the competition.External search and acquisition of technology have been going on for decades,but as Chesbrough(2003)explains,‘Open Innovation’is now a mandate for enterprise success.The concept and practice of open innovation underscore the importance of broad-based external search and subsequent integration involving cus-tomers,suppliers,and complementors.Establish-ing linkages between corporations and universities assists broad-based search,as university programs are usually unshackled from the near at hand. Indeed,a recent study of patenting in the opti-cal disk industry(Rosenkopf and Nerkar,2001) seems to suggest that exploration that is more con-fined generates lower impacts,and that the impact of exploration is highest when exploration spans organizational(but not technological)boundaries. However,it is not just a matter of searching for external inventions/innovations that represent new possibilities.Frequently it is a matter of combining complementary innovations so as to create a solu-tion to a customer problem.The systemic nature (Teece,2000)of many innovations compounds the need for external search.Sensing opportunities and threats can also be facilitated if the enterprise and/or the entrepreneur explicitly or implicitly employ some kind of ana-lytical framework,as this can help highlight what is important.Thefield of strategic management has been stranded for some time with a frame-work that implicitly assumes that industry struc-ture(and product market share),mediated by enterprise behavior,determines enterprise perfor-mance.In Porter’s(1980)Five Forces frame-work,a good strategy involves somehow picking an attractive industry and positioning oneself to be shielded from competition.Porter’s approach mandates‘industry’analysis7and the calibration offive distinct industry-level forces:the role of 7The Five Forces framework undergirds‘industry’analysis in business school curriculum and in practice.However,the very。

Vortex Mixer F202A0173 产品说明书

Vortex Mixer F202A0173 产品说明书

Instruction ManualManuale di istruzioniManu el d’instructionsManual de instruccionesBedienungsanleitung指导手册CLASSIC Vortex MixerF202A0173General Information / Informazioni Generali / Informations Générales / Información General / Allgemeine Hinweise / 一般信息Before using the unit, please read the following instruction manual carefully.Prima dell’utilizzo dello strumento si raccomanda di leggere attentamente il seguente manuale operativo.Avant d’utiliser l’instrument, il est recommandé de lire a ttentivement le présent manuel d’instructions.Antes de utilizar el instrumento, le recomendamos que lea con atención el siguiente manual de funcionamiento.Bitte lesen Sie vor Inbetriebnahme des Geräts diese Bedienungsanleitung sorgfältig durch在使用本装置之前,请仔细阅读以下使用说明书。

Do not dispose of this equipment as urban waste, in accordance with EEC directive 2002/96/CE.Non smaltire l’apparecchiatura come rifiuto urbano, secondo quanto previsto dalla Direttiva 2002/96/CE.Ne pas recycler l’appareil comme déchet solide urbain, conformément à la Directive 2002/96/CE.No tirar el aparato en los desechos urbanos, como exige la Directiva 2002/96/CE.Dieses Gerät unterliegt der Richtlinie 2002/96/EG und darf nicht mit dem normalen Hausmüll entsorgt werden.根据EEC指令2002/96/CE,请不要将本设备作为城市垃圾处理。

前列腺不典型小腺泡增生

前列腺不典型小腺泡增生
2 A SA P与前列腺微小癌鉴别指标
ASAP与前列腺微小癌 (m inimal volume p rostatic adeno2 carcinoma,癌占活检组织总量的 5%以下 )之间的鉴别标准 中 ,腺泡数目和病灶大小是最主要的一条 , ASAP腺泡的数目 是癌腺泡数目的 2 /3 (11、17) , ASAP病灶比癌性病灶小一半 (014 mm、018 mm ) 。核增大 、明显的核仁 、核分裂象 、腔内蓝 色黏液及并存 P IN等形态特征在前列腺微小癌中更明显 ,但 核深染及中 ~重度萎缩在 ASAP 比癌中更为常见 (分别为 44%、9%和 59%、35% ) 。 100%前列腺微小癌呈浸润性生 长 ,但浸润性的生长方式也存在于 75%的 ASAP病例中 。嗜 酸性颗粒性分泌物与类晶体在两者无明显差异 [12 ] 。
前列腺癌占男性恶性肿瘤的第 2位 ,在发达国家 ,前列 腺癌占全部恶性肿瘤的 19% ,在发展中国家为 513% [1 ] 。前 列腺穿刺活检是发现和确诊前列腺癌的重要手段 ,但穿刺标 本中经常会遇到少量不典型腺泡 ,疑似癌却又不能确定为 癌 ,这便是前列腺不典型小腺泡增生 ( atyp ical small acinar p roliferation, ASAP) 。现将 ASAP形态特征 、诊断标准 、发病 率 、临床意义以及对发现前列腺癌的预测价值等作一综述 。
1 A SA P的病理特征及应用现状
ASAP也称不典型腺体 ( atyp ia / atyp ical glands) [2 ] ,是由 Bostw ick等 [3 ]于 1993年首次提出的一个描述不典型腺样前 列腺增生的诊断术语 。4 年后这一诊断的临床意义得到首 次阐述 [4 ] 。
ASAP为不典型腺泡病变 ,表现为排列紧密的灶性增生 的小腺泡集落 。这些小腺泡被覆一层几近透明的分泌细胞 上皮 ,而基底细胞呈断片状或消失 (可经 34βE12 免疫组化 证实 ) 。组织特点为 : ①有限数量的腺体 ; ② 极少腺体出现 细胞不典型性 ,包括核增大 、核仁增大 ; ③ 组织异型 :缺乏核 异型的小腺泡杂乱无章地排列 ; ④ 腔内可见蓝色黏液 、结晶 体或粉红色蛋白样分泌物 [5 ] 。这些腺泡的结构形态和 /或细 胞形态类似于分化较好的前列腺癌 ,但数量太少 ,只是怀疑 为癌但不能明确诊断 。不足以诊断为癌而做出 ASAP这一 诊断主要见于两种情况 [6 ] : ①质的方面 ,缺乏足够的前列腺 癌细胞和组织结构特点 。例如一个病灶可能包括 12 个腺 泡 ,腺泡缺乏基底细胞层 ,呈浸润性生长 ,但细胞形态和组织 结构上尚未达到癌的诊断标准 (如缺少明显的核仁和明显 的核增大 ) ; ②量的方面 ,包含的腺泡数量太少 ,腺泡的细胞 和组织结构方面已经达到癌的诊断标准 ,但病灶的大小是其 主要限制 (如 1~3个腺泡 ) 。

Vocb62001

Vocb62001.docCET6 Vocabulary Test1. The world owes ________ to Prince Henry for the development of craft that made oceanic exploration possible.A. liabilityB. reputationC. creditD. gratitude2. We were working _________ time to get everything ready for the exhibition.A. inB. onC. withD. against3. When trapped in drifting sands, do not struggle, or you will be ________ in deeper.A. suckedB. heavedC. absorbedD. plunged4. Several little boats _______ the sailing ship into the harbour.A. escortedB. esteemedC. entailedD. endeavour5. There are no houses for sale in the _______ of our district.A. lodgingB. vergeC. vicinityD. inhabitation6. When you have got your ideas ______, you have next to find the best way of putting them over.A. extractedB. revolvedC. conveyedD. formulated7. When your muscle starts to get _______ you know it’s time to get more exercise.A. tenseB. briskC. brittleD. slack8. She was so angry that she _______ him across the face.A. smashedB. slammedC. slashedD. slapped9. One of the multinationals is expected t make a take-over _______ for the engineering company.A. transferB. bidC. offerD. shift10. I like to g swimming early in the morning, when the pool is largely _______ .A. insulatedB. unoccupiedC. desertedD. vacant11. I’d run out of cigarettes and was ________ to smoking the butts left in the ashtrays.A. inducedB. deducedC. reducedD. tempted12. “I’ve lost my wallet.” “It _______ you right for not putting it in a safe place.”A. suitsB. servesC. paysD. deserves13. The boy _______ a feeling of pride over his recent success.A. formulatedB. reinforcedC. accumulatedD. fostered14. The farmers are sending their cows and horses to _______ in the pasture.A. grazeB. roamC. hailD. stroll15. It’s _______ of the change in Rachel that this year she’s having a big birth day party.A. inclusiveB. indicativeC. imperativeD. imaginative16. Thoughtless vacationers had ________ the beach with cigarette packages and beer cans.A. litteredB. spoiledC. scatteredD. spotted17. In fact, about one hotel guest in three steals something from his or her room, ________ a total annual loss of over 500million.A. accounting forB. ranging fromC. consisting ofD. amounting to18. After his father died he assumed the presidency of the plant and ________ the company distinguished service.A. packedB. endowedC. surrenderedD. rendered19. When he finally emerged form the cave after 30 days, John was ________ pale.A. enormouslyB. startlinglyC. uniquelyD. dramatically120. They’re trying to ________ their costs, so staff who leave are not being replaced.A. exploitB. tackleC. trimD. unload21. Progress has been made in ________ inflation.A. curingB. curbingC. curlingD. cursing22. I don’t think this question is ________ to the main aim of our company.A. proneB. subjectC. immuneD. subordinate23. Out of ________ revenge, he did his worst to blacken her character and ruin her reputation.A. sheerB. integralC. pureD. queer24. Obviously, the two sets of policies overlap and can _______ each other.A. complimentB. complementC. contaminateD. contemplate25. These proofs of kindness and generous feeling will forever be ________ in my memory.A. perchedB. attachedC. cherishedD. clung26. The criminal ran away form the village, but he soon fell into the ________ of the military police.A. clashesB. clutchesC. circusD. criterion27. Her _______ refusal disappointed him very much when he invited her to the party.A. bleakB. bluntC. obscureD. feminine28. The independence of Androrra from France and Spain is by no means _______ .A. tentativeB. nominalC. negligibleD. narrative29. The President has accused two cabinet ministers of working secretly to ________ his position.A. underlieB. undertakeC. underlineD. undermine30. The island far way from the mainland is a favorite __________ of birds.A. dwellerB. hauntC. retreatD. territory31. His lack of a college degree is a definite _________ . Otherwise he would get a better job.A. meritB. fakeC. minusD. handicap32. The students showed _________ when solving some difficult problems.A. ingenuityB. momentumC. innovativeD. highlight33. When the neighbors were __________ with her, they call her name.A. at faultB. at oddsC. at worstD. at a distance34. The recent downward ________ of home prices has depressed the market..A. spellB. spouseC. spectacleD. spiral35. After a great deal of research the psychologist finally produced _________ evidence to support her theories about humanbehavior.A. intenseB. accumulativeC. empiricalD. analytic36. They _______ the abolition of the established system but propose nothing to replace them.A. preachedB. pleadedC. pledgedD. perished37. Not knowing he had _________ with his girl friend, I made the mistake of inviting them both to the party.A. dropped outB. fallen outC. messed upD. geared up38. Puritans believed that God _______ his will in the present world in the lives of individual men, communities, and nations.A. upheldB. contemplatedC. denotedD. manifested39. His poetry is distinguished by its nobility of ________ and simplicity of language.A. compassionB. sensationC. sentimentD. orientation40. Unlike the simple machines of the early 1900s, today’s automobiles are quite _______ .A. comprehensiveB. sophisticatedC. exquisiteD. compact241. The smoke just ________ our eyes so I move that smoking be absolutely prohibited in the conference room.A. distressesB. distortsC. irritatesD. intervenes42. There is another ________ to this problem which you haven’t mentioned.A. dimensionB. magnitudeC. scopeD. prototype43. There are several possible explanations for the greater job ________ in Japan in contrast to the great job mobility in the US.A. originalityB. securityC. sensitivityD. stability44. She took out the blood clothes to ________ the claim of the suspected.A. contradictB. reverseC. refuteD. rectify45. The monitor ________ himself by his performance in the examination.A. weighedB. evaluatedC. nominatedD. distinguished46. I _______ an e-mail to my good friend via Internet to tell him that I would visit him next week.A. dispatchedB. assignedC. attachedD. allocated47. With p rices _________ so much, it’s hard for the firm to plan a budget.A. shrinkingB. swingingC. fluctuatingD. vibrating48. More and more Chinese are learning foreign languages, ________ English.A. preciselyB. previouslyC. practicallyD. predominately49. The arrow _________ through the target just in the centre.A. persecutedB. piercedC. penetratedD. plunged50. In one scene of Modern Times, Charlie Chaplin was shown trying _______ to keep in time with a rapid assembly line.A. receptivelyB. idlyC. desperatelyD. vigorously51. Computers can provide information which allows businessmen to _________ their list of goods, by showing which items arebeing sold and how fast they are moving.A. keep track ofB. keep pace withC. keep in touch withD. keep company with52. Bacteria are sometimes _______ too small to be seen without a microphone.A. farB. fairlyC. quiteD. rather53. Charles Ives’s music was hardly popular with the public at the time it was wr itten in that it was thought to b e ________impossible to perform.A. all butB. nothing butC. anything butD. none but54. The highway was blocked, so we went by a(n) ________ road.A. selectiveB. chosenC. alternativeD. optional55. Tim is too young to be able to ________ between right and wrong.A. discernB. disperseC. diffuseD. diagnose56. The Timber rattlesnake is extinct in two eastern states in which it once _______ .A. thrivedB. prevailedC. prosperedD. flourished57. My favorite radio song is the one I first heard on a thick 1923 Edison disc I ________ at a garage sale.A. trifled withB. scraped throughC. stumbled uponD. thirsted for58. Biotechnology stands to _______ electronics in dollar volume and perhaps surpass it in social impact by 2020.A. contendB. contestC. rivalD. strive59. For three-quarters of its span on Earth, life evolved almost ________ as microorganisms.A. preciselyB. instantlyC. initiallyD. exclusively60. The introduction of gunpowder gradually made the bow and arrow _________, particularly in Western Europe.A. obscureB. obsoleteC. optionalD. overlapping61. The future of this company is _______: many of its talented employees are flowing into more profitable net-based businesses.3A. at oddsB. in dilemmaC. in vainD. at stake62. What seems confusing or fragmented at first might well become ________ a third time.A. clean and measurableB. pure and wholesomeC. clear and organicD. notable and systematic63. A leading member should never concentrate all his attention on one or two problems, to _______ of others.A. displacementB. eliminationC. exceptionD. exclusion64. The boys and girls liked to _________ together round the camp fire telling stories and singing songs.A. padB. packC. squeezeD. cluster65. The economy question as well as other issues is to be discussed when the Congress is in _______ again.A. assemblyB. sessionC. conjunctionD. convention66. The newly-elected President says the election was ________ compliance with the law.A. immenseB. exclusiveC. substantialD. ultimate67. I will ________ the truth of what he has said.A. run intoB. abide byC. step intoD. answer for68. We ________ our competitors by our products onto the market first.A. convincedB. anticipatedC. resolvedD. overwhelmed69. The boss didn’t have time so far to describe it ________, but he gave us an idea about his plan.A. without failB. under wayC. on handD. at length70. Changing from solid to liquid, water takes in heat from all substances near it, and this _______ produces artificialcold surrounding it.A. absorptionB. transitionC. consumptionD. interaction71. The European Community _________ the Single European Market on 1st January 1993.A. installedB. inauguratedC. commencedD. emitted72. During the construction of skyscrapers, cranes are used to _________ building materials t the upper floors.A. tossedB. towC. hoistD. hurl73. Mary’s father ________ with happiness when she won a world champion in swimming.A. explodedB. snappedC. glowedD. gleamed74. There could have been a war over it, but in the end reason ________ .A. countedB. probedC. dominatedD. prevailed75. He is such a shy boy that when he speaks in public he often _________ over his words.A. stumblesB. tumblesC. rumblesD. staggers76. The dogs had been on the _______ of the fox for several miles, but they lost it near the river.A. sceneB. scentC. fragmentD. fragrance77. There was a ________ underneath the photograph to show when and where it was taken .A. scriptB. captionC. marginD. index78. People often regret a _______ statement made in the heat of an argument.A. rashB. prudentC. blushD. fury79. Interestingly a(n) _________ idea or reason is often believable.A. incredibleB. recklessC. exoticD. stereotype80. There are some children who remain as ________ because they lack a particular hormone for growth.A. trampsB. clansC. dwarfsD. victims4。

1-s2.0-S0308814612005365-main

Chitosan–tripolyphosphate submicron particles as the carrier of entrapped rutinK.Konecsni,N.H.Low,M.T.Nickerson ⇑Department of Food and Bioproducts Sciences,University of Saskatchewan,51Campus Drive,Saskatoon,SK,Canada S7N 5A8a r t i c l e i n f o Article history:Received 24June 2011Received in revised form 14February 2012Accepted 19March 2012Available online 28March 2012Keywords:ChitosanSodium tripolyphosphate RutinControlled deliverySimulated gastric conditionsa b s t r a c tChitosan (CH)–tripolyphosphate (TPP)submicron particles were formed as carriers of entrapped rutin,and the release properties characterized using simulated gastric juices and fluids of the small intestine.Particle size,charge and entrapment efficiencies were investigated as a function of the CH:TPP molar ratio (2.0:1.0–5.0:1.0).Size was found to decrease from $814nm for the 2.0:1:0mass ratio to $528nm for the ratios between 2.5:1.0and 4.0:1.0,and then again to $322nm for the 5:0:1.0mass ratio,whereas all par-ticles carried a positive surface charge,increasing from +21to +59mV as the ratio increased from 2.0:1.0to 5.0:1.0.The percent entrapment was found to rise from 3.68%to 57.6%as the ratios increased from 2.0:1:0to 4.0:1:0,before reaching a plateau.Submicron particles (4.0:1.0mass ratio only)were found to retain rutin in simulated gastric fluids,whereas in conditions which simulated fluids from the small intestine,only 20%of the entrapped rutin was released and 80%remained absorbed to the CH:TPP carri-ers.Such particles have applications for the delivery of phenolics in food and natural health products.Ó2012Elsevier Ltd.All rights reserved.1.IntroductionThe interest in antioxidants is increasing in the food,nutraceu-tical and natural health product sectors because of their purported ability to protect the body against reactive oxygen and nitrogen species (Shahidi &Naczk,2004).However,the inclusion of more concentrated extracts than is normally naturally present in foods is hindered from off-flavours,poor stability and reduced solubility.The use of encapsulation technology has been shown to help cir-cumvent these issues by entrapping the phenolic compounds with-in biopolymer carriers to better control the dosage,improve their stability against oxidation,provide site-specific targeted delivery,mask off-flavours and improve their miscibility in aqueous food products.Previously,phenolic compounds have been entrapped within carriers comprised of alginate (Deladino,Anbinder,Navarro,&Martino,2008),cellulose (Lauro,Maggi,Conte,De Simone,&Aquino,2005),chitosan (Hu et al.,2008;Kosaraju,D’Ath,&Lawrence,2006;Zhang &Kosaraju,2007),cyclodextrins (Lucas-Abellan,Fortea,Gabaldon,&Nunez-Delicado,2007),gelatin (Shutava et al.,2009),barley glucan (Xiong,Melton,Easteal,&Siew,2006),maltodextrins (Laine,Kylli,Heinonen,&Jouppila,2008;Robert et al.,2010)and triacylglycerols (Barras et al.,2009).The overall goal of this research was to investigate the use of chitosan (CH)–tripolyphosphate (TPP)submicron particles as carriers of entrapped rutin,and to study their release properties in simulated gastric juices and fluids of the small intestine.Rutin was chosen as a source of the flavonoid quercetin,which is known for its strong antioxidant activity.Chitosan is a naturally occurring cationic polysaccharide derived by the deacetylation of chitin,comprising of repeating b -(1?4)-2-amino-2-deoxy-D -glucopyra-nose units.Chitosan is widely used in controlled delivery applica-tions due to its mucoadhesive properties (Grabovac,Guggi,&Bernkop-Schnürch,2005;Woodleym,2001),biocompatibility and cationic nature (Bonferoni,Sandri,Rossi,Ferrari,&Caramella,2009;Pedro,Cabral-Albuquerque,Ferreira,&Sarmento,2009).The formed nanoparticles are typically stabilized through electro-static cross links between the amino groups along the CH backbone and negatively charged tripolyphosphate (TPP)salts (Janes,Calvo,&Alonso,2001;Mi,Shyu,Lee,&Wong,1999).Chitosan–TPP matrices have been previously used to entrap bo-vine serum albumin (Rayment &Butler,2008),ascorbic acid (Jang &Lee,2008),antimicrobials (Qi,Xu,Jiang,Hu,&Zou,2004),dorzola-mide and pramipexole (Papadimitriou,Bikiaris,Avgoustakis,Kara-vas,&Georgarakis,2008),and phenolics including tea catechins (Hu et al.,2008;Zhang &Kosaraju,2007)and quercetin (Zhang,Yang,Tang,Hu,&Zou,2008).In terms of phenolic entrapment and release,the aforementioned studies differed from the present study in terms of both their entrapment and/or in vitro release experimental ap-proach.Zhang and Kosaraju (2007)entrapped tea catechins within freeze-dried CH:TPP particles,followed by characterization of their entrapment efficiencies,size and charge.The authors reported the freeze drying process resulted in irreversible aggregation of multiple nanoparticles giving micron-sized ($4–7l m)particulates.In vitro release behaviour was also investigated within enzyme-free simu-lated gastric and intestinal conditions.Hu et al.(2008)conducted a0308-8146/$-see front matter Ó2012Elsevier Ltd.All rights reserved./10.1016/j.foodchem.2012.03.070Corresponding author.Tel.:+13069665030;fax:+13069668898.E-mail address:Michael.Nickerson@usask.ca (M.T.Nickerson).more comprehensive study focusing on CH:TPP design for the entrapment and release of similar phenolics(catechins).The authors investigated the effect of modulating conditions of CH–tea catechin contacting time,CH characteristics(size and concentration),CH:TPP molar ratio,initial pH of the CH solution and concentration of cate-chins in relation to the entrapment efficiency and in vitro release behaviour from the formed nanoparticles.The authors reported the possibility of tailored release based on capsule design;however in vitro studies were limited to heating of the nanoparticles in deion-ized water at37°C rather than under simulated gastric conditions. Zhang et al.(2008)investigated the use of CH:TPP nanoparticles to entrap quercetin,probing the particle structure and retained antiox-idant activity in vitro using a free radical scavenging activity test and reducing power test.The authors reported that their nanoparticle design was effective at maintaining the bioavailability of the querce-tin once entrapped.The present study builds upon gaps in literature by studying aqueous CH:TPP submicron particles(without drying)in terms of their entrapment efficiencies,size and charge,and perform-ing in vitro studies using simulated intestinalfluids with enzymes.2.Materials and methods2.1.MaterialsChitosan powder(low molecular weight92%deacetylated)was purchased from Sigma–Aldrich(Oakville,ON,Canada),along with the Folin–Ciocalteu’s(FC)phenol reagent,porcine pancreatin,rutin hydrate and sodium tripolyphosphate.Hydrochloric acid(HCl),so-dium bicarbonate(NaHCO3),acetic acid(glacial),acetonitrile (HPLC grade),sodium chloride(NaCl)and oxgall dehydrated bile media was obtained through VWR(Mississauga,ON,Canada), whereas ethanol(95%v/v)was purchased from Commercial Alco-hols Inc.(Brampton,ON,Canada).Gases used for in the anaerobic chamber were purchased from Praxair(Saskatoon,SK,Canada) and consisted of a80%N2,10%H2and10%li-Q water(Milli-Q water system,Millipore,Billerica,MA,USA)was used for all experiments(denoted as ddH20).2.2.Preparation of chitosan–tripolyphosphate particlesChitosan particles were prepared using the ionic gelling tech-niques of Zhang and Kosaraju(2007)and Jang and Lee(2008)with minor modifications.The particles were prepared at different CH:TPP(w/w)ratios of 2.0:1.0, 2.5:1.0, 3.0:1.0, 4.0:1.0and 5.0:1.0,with entrapped rutin.The chitosan solutions were pre-pared by dissolving CH powder(Sigma,Oakville,ON)at the follow-ing concentrations(2.4,3.0,3.6,4.8,6.0±0.2mg/ml)in a10ml solution containing2.0ml acetic acid10%(v/v)and8.0ml of70% (v/v)ethanol(containing1mg/ml of rutin,prepared by sonication of the rutin powder within ethanol for30min).The solution was then mixed at480rpm using a magnetic stirrer(Ika,Wilmington, NC)until complete dissolution occurred($10min).The solution pH was adjusted to4.8using1.0M sodium hydroxide(NaOH) ($100l l),and was allowed to stir for an additional3h at 250rpm.Sodium tripolyphosphate(TPP)(0.075%w/v)was added (6ml,2mg/ml)drop-wise to the mixture,and allowed to stir for 1h for particle hardening.The chitosan particles were separated by centrifugation(Beckman J2-HC,Mississauga,Ontario)at 9820g for30min.The supernatant was used to determine the entrapment efficiencies,whereas the pellet was used in the release, sizing and surface charge studies.2.3.Entrapment efficienciesEntrapment efficiencies for rutin within the CH–TPP submicron particles was determined by analyzing the supernatant relative to their original concentrations(Zhang,Oh,Allen,&Kumacheva, 2004).The analyses were made using high performance liquid chromatography(HPLC)with photodiode array detection(PAD) and the Folin–Ciocalteau(FC)method.All analyses were performed in triplicate.2.3.1.HPLC–PDAHPLC–PDA(1100series HPLC system,Agilent Technologies Can-ada Incorporated,Mississauga,ON)was used to determine rutin levels within the supernatant relative to a single point standard (8.0mg rutin in2.0ml[10%(v/v)]acetic acid:8.0ml[70%(v/v)] ethanol:6.0ml[2mg/ml]TPP).All supernatants were loaded onto a250Â4.6mm Prodigy ODS-3,5l m,C18column(Phenomenex, Torrance,CA)in series with a C18guard cartridge(Phenomenex, Torrance,CA)at25°C.Sample injection volume was set at20l l with mobile phases consisted of ddH2O(solvent A)and acetonitrile (solvent B).Theflow rate was0.8ml/min and the following gradi-ent system was used:initial,100%A followed by linear gradient to 55%B at15min.The sample injection volume was20l l and all samples were syringefiltered before analysis.Detection was per-formed using a PDA with monitoring at254,280,360and520nm.2.3.2.FC methodFC method was adapted from Singleton,Orthofer,and Lamuela-Raventos(1999)to determine the rutin levels within the supernatant.One millilitre of supernatant was passed through a nylon syringefilter(13mm diameter,0.2l m pore size;Chro-matographic Specialties Inc.,Brockville,ON)and added to5.0ml of1:10(v/v)of FC phenol reagent in glass test tubes (16Â150mm).After5min,4.0ml of15%(w/v)sodium carbonate was added to each tube,which were then covered and mixed by inversion.The samples then stood for2h at room temperature (22±2°C)before analysis.A blank was prepared which contained all of the reagents plus 1.0ml of ddH2O.After the incubation period,the samples were analyzed by UV–visible spectroscopy (Mecasys Co.,Daejeon,South Korea)at765nm.Standards of rutin were prepared at concentrations of0.5and2.5mg/ml.All stan-dards and samples were run in triplicate.2.4.Particle sizeParticle size was determined for all CH:TPP ratios containing rutin(2.0:1.0,2.5:1.0,3.0:1.0,4.0:1.0,5.0:1.0)using a Zetasizer Nano Series instrument(Malvern Instruments,Westborough, MA).The recovered pellet(Section 2.2)was re-suspended in 10.0ml of ddH2O and left to stir overnight at250rpm.A0.5ml aliquot of this solution was then diluted with9.5ml of ddH2O and sonicated for10min before size determination at room tem-perature within a plastic cuvette(1cm path length)to break up any aggregated particles.All samples were measured in triplicate.2.5.Zeta potentialThe zeta potential(f)of CH–TPP particles(with rutin)was estimated by measuring the electrophoretic mobility(U E)using a folded capillary cell with the aforementioned Zetasizer Nano Series instrument.The f was estimated using the Henry equation:U E¼2e f fðj aÞ3gð1Þwhere,e is the dielectric constant,f(ja)is the Smoluchowski approximation(equivalent to1.5),and g is viscosity.One millilitre of the diluted re-suspended particles for all CH:TPP ratios was used for analysis.All measurements were made in triplicate.1776K.Konecsni et al./Food Chemistry134(2012)1775–17792.6.Release studies within simulated2.6.1.Simulated gastricfluid(SGF)Rutin release from CH:TPP4.0:1.0ratio in SGF was investigated and Kosaraju(2007).SGJ was prepared 3.5ml12M HCl within a500ml brought to volume with ddH2O(pH wet pellet)(0.7–0.8g)were dispersed bated at37°C in a water bath ($100rpm).Aliquots(250l l)were 120min.Samples were thenfiltered content by HPLC–PDA.All experiments 4:0:1.0CH:TPP ratio was selected as the size,surface charge and entrapment and as such were the only ratio tested.2.6.2.Simulated intestinalfluid(SIF)Rutin release from CH:TPP4.0:1.0ratio in SGF was investigated et al.(2007).SIF was prepared by drated bile media,12.5g NaHCO3and volumetricflask and was brought to creatin enzyme mixture comprised of protease(100USP units/mg),lipase known concentration).SIF were then chamber for12h prior toGA;80%N2,10%H2and10%CO2;37°wet pellet)(0.7–0.8g)were dispersed in at37°C within the aerobic chamber ($100rpm).Aliquots(250l l)were 45,60,120,180,240min;syringed PDA.All experiments were performed 2.7.StatisticsAll statistical analyses were performed using SPSS software (SPSS Ver.17.0,Chicago,IL).A one-way analysis of variance (ANOVA)with a post-hoc Tukey test was used to determine statis-tical significance(p60.05).3.Results and discussion3.1.Particle size and surface chargeParticle size and surface charge are both important consider-ations when designing controlled delivery vehicles.Sub-micron particles are essential for mucosal and epithelial tissue uptake, whereas particles of high positive charge aid in suspension stabil-ity,mucoadhesiveness and permeation(Harris,Lecumberri,Mat-eos-Aparicio,Mengíbar,&Heras,2009;Hu et al.,2008).Chitosan-based particles were formed by ionotropic cross-linking with TPP at different mass ratios(2.0:1.0–5.0:1.0CH:TPP).In general,the CH:TPP particles experienced a decline in size with increasing mass ratio(Fig.1A)as the geometric mean diameter of the particles de-creased from$814nm for the2.0:1:0mass ratio to$528nm for ratios between 2.5:1.0and 4.0:1.0,and to$322nm for the 5:0:1.0mass ratio.In solution,the anionic phosphate groups in TPP interact with an extended CH polymer(under acidic condi-tions)as follows:first by forming intermolecular and intramolecu-lar cross-links between amino groups along the CH backbone;and second by screening occupied or unoccupied charged reactive sites to reduce the overall surface charge of the polysaccharide(Mi et al., 1999).This screening effect acts to reduce the polymer’s electric double layer and increase its conformational entropy(or chain flexibility)(Mi et al.,1999).Hu et al.(2008)reported a linear de-cline in particle size with increasing CH:TPP mass ratios from 3.0:1:0to7:0:1:0.The authors attributed the larger particles at lower mass ratios(i.e.,more TPP present relative to available —NHþ3groups)to the cross linking of multiple smaller mono-parti-cles to give an overall larger cluster in solution.In contrast,at high-er mass ratios(i.e.,where TPP is more limiting)fewer inter-particle cross links may be formed.In the current study,surface charge of the formed CH:TPP par-ticles were found to increase from$+21to$+59mV as the mass ratio increased from2.0:1.0to5.0:1.0indicating that less neutral-ization of protonated amino groups by TPP was taking place(i.e., TPP was becoming limiting)and that more CH sites were left un-bound as polysaccharide levels increased(Fig.1B)(p<0.05).The positive zeta potential over the entire molar range indicates thateven at the low 2.0:1.0mass ratio,there are unbound—NHþ3 groups present(Harris et al.,2009).The significantly lower zeta po-tential at a mass ratio of2.0:1.0may reflect the electrostatic charge screening effect of TPP(Liu&Gao,2009)and the larger clustering of the CH particles due to TPP ionic cross linking(Zhang&Kosaraju, 2007).The latter would results in less protonated amino groups at the surface,which are exposed to the solvent(Fig.1B).A similar trend was also reported by Hu et al.(2008)for CH:TPP systems at slightly higher mass ratios(3.0:1.0–7.0:1.0).3.2.Entrapment of rutinIn the current study,the entrapment efficiencies of rutin were indirectly measured by determining rutin content in the Size(A)and zeta potential(B)of CH:TPP rutin particles as a function ofat pH4.8.The data represent the mean±one standard deviation(n=3).Means common letters are not significantly different(p60.05).supernatant so as to estimate the levels entrapped within the CH:TPP particles.These levels were investigated as a function of CH:TPP mass ratio as determined by HPLC–PDA and the FC assay (Fig.2).The percent entrapment efficiency(%EE)(as measured by HPLC–PDA)was found to increase from3.7±1.4%to57.6±5.1% as the CH:TPP ratios increased from2.0:1:0to4.0:1:0,respectively (p<0.05),after which a plateau was reached up to the5.0:1:0ratio (p>0.05)(Fig.2A).A similar trend was found using the FC assay where%EE increased from9.0±6.1%up to62.1±6.1%as ratios in-creased from a CH:TPP ratio of2.0:1.0to4.0:1.0(p<0.05),respec-tively,before levelling off(p>0.05)(Fig.2B).The rise in%EE with an increasing CH:TPP ratio(up to4.0:1.0)is thought to be associ-ated with the larger number of charged—NHþ3groups available for interactions with rutin through hydrogen bonding(Zhang& Kosaraju,2007).Once the plateau was reached(4.0:1.0mass ratio), the rutin concentration is thought to become limiting relative to nisms of interactions.In the present study,TPP acts to form inter-molecular and intramolecular electrostatic cross links within or between neighbouring CH chains,and also to screen the electric double layer so as to reduce the electrostatic attractive forces act-ing towards counterions(or counter-molecules)in solution.At low mass ratios(2.0:1.0CH:TPP),available—NHþ3groups are reduced due to higher levels of TPP leading to less hydrogen bonding be-tween CH and rutin(%EE$3.7%).However,as the mass ratio in-creased(i.e.,increase the CH content relative to TPP),the amountof available—NHþ3groups increased allowing for greater hydrogen bonding to occur between CH and rutin.Increased hydrogen bond-ing leads to higher%EE values,which reflects both entrapped rutin within the CH:TPP submicron particles(or aggregates)and that ab-sorbed on their surface.3.3.In vitro release studiesPercent entrapment efficiency of rutin as a function of CH:TPP mass ratio,determined by(A)HPLC–PDA and(B)the FC assay.Data represent the mean standard deviation(n=3).Means with common letters are not significantly different(p>0.05).3.Percent release of rutin from CH:TPP particles(4.0:1.0mass ratio)within simulated intestinalfluid as a function of time(min)as measured by HPLC–PDA.represent the mean±one standard deviation(n=3).1778K.Konecsni et al./Food Chemistry134(2012)1775–1779literature,relates to both material characteristics(e.g.,CH molecu-lar weight/molar ratio,TPP levels and bioactive core material), along with the in vitro assay employed(e.g.,pH,duration,en-zymes,and salts).Zhang,Alsarra,and Neau(2002)found that the CH:TPP particles released only20–40%of their entrapped material (bovine serum albumin)after20h in SIF with enzymes.Hu et al. (2008)reported$45–55%release of entrapped catechins from the CH:TPP nanoparticles depending on the mass ratio after12h of emersion in distilled water at37°C.4.ConclusionsIn summary,the particle designs were found to be optimal at a 4.0:1.0CH:TPP mass ratio for carrying rutin,where the particles car-ried a high positive charge to promote mucoadhesion.The particles were sufficient in size to facilitate absorption across the intestinal wall,and had good entrapment efficiencies.The particles were also able to retain the sensitive core material(rutin)through simulated stomachfluids,and release a portion of its contents($20%release) in simulated intestinal conditions.Carrier designs could be used for the delivery of concentrated extracts of phenolic compounds in food and natural health products,however further work is needed to increase the bioactive load,the release rates and elucidate the mechanisms associated with the matrix degradation.AcknowledgementFinancial support from this research was provided by the Ad-vanced Foods and Materials Network.ReferencesBarras,A.,Mezzetti,A.,Richard,A.,Lazzaroni,S.,Roux,S.,Melnyk,P.,et al.(2009).Formulation and characterization of polyphenol-loaded lipid nanocapsules.International Journal of Pharmaceutics,379,270–277.Bonferoni,M.C.,Sandri,G.,Rossi,S.,Ferrari,F.,&Caramella,C.(2009).Chitosan and its salts for mucosal and transmucosal delivery.Expert Opinion on Drug Delivery, 6,923–939.Deladino,L.,Anbinder,P.S.,Navarro,A.S.,&Martino,M.N.(2008).Encapsulation of natural antioxidants extracted from Ilex paraguariensis.Carbohydrate Polymers, 71,126–134.Grabovac,V.,Guggi, D.,&Bernkop-Schnürch, A.(2005).Comparison of the mucoadhesive properties of various polymers.Advanced Drug Delivery Reviews,57,1713–1723.Harris,R.,Lecumberri,E.,Mateos-Aparicio,I.,Mengíbar,M.,&Heras,A.(2009).Chitosan nanoparticles and microspheres for the encapsulation of natural antioxidants extracted from Ilex paraguariensis.Carbohydrate Polymers,84, 803–806.Hu,B.,Pan,C.,Sun,Y.,Hou,Z.,Ye,H.,Hu,B.,et al.(2008).Optimization of fabrication parameters to produce chitosan–tripolyphosphate nanoparticles for delivery of tea catechins.Journal of Agricultural and Food Chemistry,56,7451–7458. Janes,K.A.,Calvo,P.,&Alonso,M.J.(2001).Polysaccharide colloidal particles as delivery systems for macromolecules.Advanced Drug Delivery Reviews,47, 83–97.Jang,K.I.,&Lee,H.G.(2008).Stability of chitosan nanoparticles for L-ascorbic acid during heat treatment in aqueous solution.Journal of Agricultural and Food Chemistry,56,1936–1941.Kosaraju,S.L.,D’Ath,L.,&Lawrence,A.(2006).Preparation and characterisation of chitosan microspheres for antioxidant delivery.Carbohydrate Polymers,64, 163–167.Laine,P.,Kylli,P.,Heinonen,M.,&Jouppila,K.(2008).Storage stability of microencapsulated cloudberry(Rubus chamaemorus)phenolics.Journal of Agricultural and Food Chemistry,56,11251–11261.Laird,B.D.,Van de Wiele,T.R.,Corriveau,M.C.,Jamieson,H.E.,Parsons,M.B., Verstraete,W.,et al.(2007).Gastrointestinal microbes increase arsenic bioaccessibility of ingested mine tailings using the simulator of the human intestinal microbial ecosystem.Environmental Science and Technology,41, 5542–5547.Lauro,M.R.,Maggi,L.,Conte,U.,De Simone,F.,&Aquino,R.P.(2005).Rutin and quercetin gastro-resistant microparticles obtained by spray-drying technique.Journal of Drug Delivery Science and Technology,15,363–369.Lin,Y.H.,Sonaje,K.,Lin,K.M.,Juang,J.H.,Mi,F.K.,Yang,H.W.,et al.(2008).Multi-ion-crosslinked nanoparticles with pH-responsive characteristics of oral delivery of protein drugs.Journal of Controlled Reselease,132,141–149.Liu,H.,&Gao, C.(2009).Preparation and properties of ionically cross-linked chitosan nanoparticles.Polymers for Advanced Technologies,20,613–619. Lucas-Abellan, C.,Fortea,I.,Gabaldon,J. A.,&Nunez-Delicado, E.(2007).Encapsulation of quercetin and myricetin in cyclodextrins at acidic pH.Journal of Agricultural and Food Chemistry,56,255–259.McConnell, E.L.,Murdan,S.,&Basit, A.W.(2008).An investigation into the digestion of chitosan(noncrosslinked and crosslinked)by human colonic bacteria.Journal of Pharmaceutical Sciences,97,3820–3829.Mi,F.L.,Shyu,S.S.,Lee,S.T.,&Wong,T.B.(1999).Kinetic study of chitosan–tripolyphosphate complex reaction and acid-resistive properties of the chitosan–tripolyphosphate gel beads prepared by in-liquid curing method.Journal of Polymer Science Part B-Polymer Physics,37,1551–1564. Papadimitriou,S.,Bikiaris,D.,Avgoustakis,K.,Karavas,E.,&Georgarakis,M.(2008).Chitosan nanoparticles loaded with dorzolamide and pramipexole.Carbohydrate Polymers,73,44–54.Pedro,A.S.,Cabral-Albuquerque,E.,Ferreira,D.,&Sarmento,B.(2009).Chitosan:An option for development of essential oil delivery systems for oral cavity care?Carbohydrate Polymers,76,501–508.Qi,L.,Xu,Z.,Jiang,X.,Hu,C.,&Zou,X.(2004).Preparation and antibacterial activity of chitosan nanoparticles.Carbohydrate Research,339,2693–2700.Rayment,P.,&Butler,M.F.(2008).Investigation of ionically crosslinked chitosan and chitosan–bovine serum albumin beads for novel gastrointestinal functionality.Journal of Applied Polymer Science,108,2876–2885.Robert,P.,Gorena,T.,Romero,N.,Sepulveda,E.,Chavez,J.,&Saenz,C.(2010).Encapsulation of polyphenols and anthocyanins from pomegranate(Punica granatum)by spray drying.International Journal of Food Science and Technology, 45,1386–1394.Shahidi, F.,&Naczk,M.(2004).Antioxidant properties of food phenolics.In Phenolics in foods and nutraceuticals,pp.1–4).New York:CRC Press. 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新世纪博士综合英语翻译Unit 2 A Deadly Drug

A Deadly Drug, A New Generation一种致命的药物,新的一代These heroin users are the kids next door-or closer这些海洛因使用者就在孩子们身边By Henry Pierson Curtis亨利.皮尔森.柯蒂斯1. Inside a nightclub, where a party known as a "rave" was under way, 16-year-old Sarah Jenkins could feel the beat of the music pulsating through the dance floor. Tall, with sandy hair, she moved with the dancers and felt her senses heighten. Her eyes took in the psychedelic light show flashing bright colors across the ceiling and walls.在一家夜总会内,有一个被称为“锐舞”的派对正在进行。

16岁的莎拉.詹金斯,高挑的身材,沙质头发,通过舞池的节奏能感觉到音乐的节拍;她随着舞者移动,感觉很兴奋;她的眼睛吸入了天花板和墙壁反射的迷幻的灯光,闪烁着明亮的色彩。

2. Raves like this one in Orlando, Fla., are the places to be for suburban teens like Sarah. And while they may appear safe, many have a sinister edge: trolling the periphery of the dance floor are dealers looking to sell marijuana, cocaine, heroin and psychedelics such as Ecstasy.像在佛罗里达州奥兰多市这个派对一样的“锐舞”派对是适合像萨拉这样的郊区青少年的地方。

辅助生殖技术相关并发症的研究进展

DOI:10.12280/gjszjk.20200730谢奇君,李欣,赵纯,凌秀凤△【摘要】辅助生殖技术(ART)已被广泛应用于不孕症的治疗,包括人工授精(AI)和体外受精-胚胎移植(IVF-ET),及其相关衍生技术如胞浆内单精子注射(ICSI)、胚胎植入前遗传学筛查(PGS)、卵母细胞体外成熟(IVM)、胚胎辅助孵化(AH)等技术。

随着ART的普及和妊娠率的逐步提高,其带来的并发症及其安全性也越来越受到重视。

能够及时发现和处理并发症,可以最大限度地使不孕症患者获得安全优质的妊娠结局。

目前,ART相关并发症发生的原因仍存在争议,有部分研究认为是由于ART导致的多胎妊娠或不孕症病因,也有研究认为是由于ART本身。

故对近年来相关文献进行分析,总结ART相关并发症的最新研究进展。

【关键词】生殖技术,辅助;并发症;不育,女(雌)性;体外受精;胚胎移植Research Progress of Complications Related to Assisted Reproductive Technology XIE Qi-jun,LI Xin,ZHAO Chun,LING Xiu-feng.Reproductive Center,Women′s Hospital of Nanjing Medical University(NanjingMaternity and Child Health Care Hospital),Nanjing210004,ChinaCorresponding author:LING Xiu-feng,E-mail:************************【Abstract】Assisted reproductive technology(ART)has been widely used in the treatment of infertility,including artificial insemination(AI)and in vitro fertilization-embryo transfer(IVF-ET),and many derivativetechniques such as intracytoplasmic sperm injection(ICSI),preimplantation genetic screening(PGS),in vitromaturation(IVM),and assisted hatching(AH).With the popularity of ART and the gradual improvement ofpregnancy rate,more and more attention has been paid to the complications of ART and the safety of ART.Detection and treatment of complications in time can maximize the safety and high quality of pregnancy,and thegood outcomes for patients.At present,the causes of ART-related complications are still controversial.Somestudies believe that the increased rate of multiple pregnancy caused by ART or the factors related to infertility arethe main causes.However,other studies believe that the factors of ART itself cannot be overlooked.In this review,we analyzed the complications related to ART and the causes.【Keywords】Reproductive techniques,assisted;Complications;Infertility,female;Fertilization in vitro;Embryo transfer(JIntReprodHealth蛐FamPlan,2021,40:204-208)·综述·基金项目:国家自然科学基金(81871210)作者单位:210004南京医科大学附属妇产医院(南京市妇幼保健院)生殖中心通信作者:凌秀凤,E-mail:************************△审校者辅助生殖技术(assisted reproductive technology,ART)是一种应用各种技术处理精子或卵子,以帮助不孕症夫妇实现生育的方法,包括人工授精(artificial insemination,AI)、体外受精-胚胎移植(invitro fertilization-embryo transfer,IVF-ET)及相关技术,如胞浆内单精子注射(intracytoplasmic sperminjection,ICSI)、胚胎植入前遗传学筛查(preimplantation genetic screening,PGS)、卵母细胞体外成熟(in vitro maturation,IVM)、胚胎辅助孵化技术(assisted hatching,AH)和卵母细胞玻璃化冷冻技术等。

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Deal or no deal?Corporate briefingDecember 2008The FSA is investigating possible breaches of the Listing Rules following the announcement by The Carphone Warehouse Group PLC of a director's share pledges as security for personal loans. This is a timely reminder that those who manage and advise listed companies must always consider the requirements of the FSA's Listing Rules, and in particular its Model Code on dealings in securities, whenever persons with managerial responsibilities want to take any action regarding their shareholdings in the listed company.CARPHONE WAREHOUSE ANNOUNCEMENT AND FSA INVESTIGATIONDavid Ross was the deputy chairman of Carphone Warehouse. On Monday 8 December 2008, Carphone Warehouse announced that it had received notification from Mr Ross that he had, through various agreements between 2006 and 2008 and as part of a package of security, pledged 136.4 million ordinary shares in the company against personal loans. Mr Ross had also tendered his resignation as a director of the company with immediate effect.Subsequent news stories in the press also suggested that he had pledged shares in other listed companies of which he was a director as collateral for loans.The FSA is investigating whether Mr Ross breached the Listing Rules by pledging the shares as collateral for loans.The Model CodeThe purpose of the Model Code is to ensure that persons discharging managerial responsibilities (PDMRs), including directors, do not abuse, and do not place themselves under suspicion of abusing, inside information that they may be thought to have. Under the Listing Rules, listed companies must require every PDMR to comply with the Model Code and must take all proper and reasonable steps to secure their compliance. Individual listed companies are free to impose more rigorous dealing obligations than those contained in the Model Code.The cornerstone of the Model Code is that PDMRs must not deal in the securities of the listed company without obtaining advance clearance. The Model Code sets out the procedures for requesting and obtaining clearance. Before dealing, a director (other than the chairman or chief executive) or company secretary must notify the chairman, or a director designated by the board for this purpose, and receive clearance to deal from him. The chairman and chief executive must obtain clearance from each other or, if the other is not available, from the senior independent director or a board committee or other officer nominated for the purpose.A PDMR may not be given clearance to deal:• in any securities of the company on considerations of a short term nature (investments witha maturity of one year or less always being considered short term);• during a "close period" (as defined in the Model Code); or• at any time when there exists any matter which constitutes inside information in relation to the listed company.PDMRs must also take reasonable steps to prevent any dealings by or on behalf of persons connected with them on considerations of a short term nature, and must seek to prohibit any dealings by or on behalf of any connected person or by an investment manager on behalf of the PDMR or on behalf of any other person connected with the PDMR during a close period. However, the PDMR should not inform his connected persons or investment manager when they are not free to deal as a result of the company having inside information in existence. "Dealing"It may not be obvious at first glance that "dealing" catches the act of pledging shares as security, as it does not involve an outright disposal of the shares. However, the Model Code sets out a list of operations, as well as straightforward acquisitions and disposals, which amount to dealing. These include "using as security, or otherwise granting a charge, lien or other encumbrance over the securities of the company" (paragraph 1(c)(v) of the Model Code).Not all dealings are caught: paragraph 2 of the Model Code sets out a list of those which may be carried out without obtaining consent. These include the take up of rights under a rights issue, undertakings to accept a takeover offer, and various transactions in connection with employee share schemes.The upshot is that where any transaction relating to shares in the listed company is involved, the provisions of the Model Code (or, if relevant, the company's own share dealing code) should be carefully checked. In addition, bear in mind that even if a transaction is not prohibited by the Model Code, it may still contravene the market abuse or insider dealing regimes.There is no express requirement under the Model Code for a listed company to announce that clearance to deal has been given. However, PDMRs and listed companies must consider carefully whether notification and announcement obligations arise under the provisions of the Listing Rules and the Disclosure and Transparency Rules, for example pursuant to DTR 3.1.2 (notification of transactions by PDMRs) and DTR 3.1.4 (notification of transactions by issuers to a RIS).CONTACTIain Newman, Partner T +44 (0)20 7524 6423 i.newman@LondonLacon House, 84 Theobald's Road, London WC1X 8RWT +44 (0)20 7524 6000F +44 (0)20 7524 6524 Sheffield1 South Quay, Victoria Quays,Sheffield S2 5SYT +44 (0)114 279 4000F +44 (0)114 278 6123Brussels209A Avenue Louise,1050 Brussels, BelgiumT +32 2 626 0740F +32 2 626 0749Alliance firms:France August & Debouzy Gilles AugustT +33 (0)1 45 61 51 80 Germany GSK Stockmann & KollegenRainer StockmannT +49 (30) 20 39 07 - 0www.gsk.deItaly Nunziante MagroneGianmatteo NunzianteT +39 06 695181www.nunziantemagrone.itSpain Rodés & SalaGonzalo RodésT +34 932 413 740Nabarro LLPRegistered office: Lacon House, 84 Theobald's Road, London, WC1X 8RW.Nabarro LLP is a limited liability partnership registered in England and Wales (registered number OC334031) and is regulated by the Solicitors Regulation Authority. A list of members of Nabarro LLP is open to inspection at the registered office. The term partner is used to refer to a member of Nabarro LLP.DisclaimerDetailed specialist advice should be obtained before taking or refraining from any action as a result of the comments made in this publication, which are only intended as a brief introduction to the particular subject. This information is correct on the date of publication. We cannot be responsible for links to external websites that may become broken in the future.© Nabarro LLP 2008。

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