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Johansson, Andreas. "Projektplaner vid y2k-projekt." Thesis, University of Skövde, Department of Computer Science, 1999. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-355.
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Detta arbete berör hur företag har arbetat med att anpassa sina verksamheter till att klara millenniumskiftet utan att problem uppstår. Jag har genomfört undersökningen genom att intervjua fem respondenter från företag som jag anser vara intressanta i sammanhanget.
Jag har i undersökningen fokuserat på hur företagen har upprättat sina projektplaner för projekten av det här slaget. Som utgångspunkt för det här har jag använt mig utav ett förslag till projektplan som 2000-delegationen har tagit fram och som innefattar åtta olika faser som de anser vara värdefulla vid ett sådant här projekt.
De slutsatser som jag har kommit fram till är att de medverkande företagen i undersökningen har använt sig av väl fungerande projektplaner, även om dessa inte är lika omfattande och kompletta som 2000-delegationens förslag. Min bedömning är att företagen generellt sett ligger bra till tidsmässigt och jag anser att de har goda förutsättningar för att klara millenniumskiftets komplikationer.
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Lee, Wonjin. "Y2K and the Economy." Miami University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami1493850006258811.
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Taunton, Roy Gwen. "Y2K Serendipity: Benefits and Spinoffs." NSUWorks, 2002. http://nsuworks.nova.edu/gscis_etd/875.
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The primary purpose of the researcher this study was to determine what, if any, unexpected benefits, spin-offs, and other "serendipitous" events occurred as a result of the year 2000 remediation process undertaken by businesses, industry, and other organizations. This was measured through the use of an online survey instrument comprised of a series of questions designed to measure and discover those benefits. The survey was sent to approximately 50 different businesses/organizations during the pilot stage of this study and 250 during the main stage of this study. These businesses/organizations were randomly selected from the sampling frame using random sampling techniques. The random samples that were used included the areas of financial services, health care, non-computer manufacturing, telecommunications, transportation, and utilities. The survey responses were analyzed in an effort to determine what benefits were common to these businesses as well as to discover possible unique benefits some business may have experienced. Of particular interest were any benefits that companies indicate were totally unexpected or serendipitous. Final analysis of the data was accomplished through the use of canonical correlation. This statistical procedure was chosen because of its usefulness in determining correlations between a set of independent variables and a set of dependent variables. The findings of the pilot study were, for the most part, inconclusive due to the small number of responses. The analysis of the data from the main study resulted in one significant canonical function. The canonical correlation between the computer generated variates created by this function was reported at approximately .86. This indicates a high degree of correlation between criterion variate I that represented the independent variables, and is the predictor variate I that represented the dependent variables. The variables PCSYS, NTSYS, MFSYS had the highest correlation with the Predictor I variate. The variables ITISS, A W AREMIA, and A WAREBF had the highest correlation with the Criterion I variate. Therefore, the independent variables PCSYS, NTSYS, and MFSYS were most predictive of the dependent variables ITISS, AWAREMIA, and AWAREBF. To determine if there were unexpected benefits in those companies surveyed, a multiple regression was performed using the measured variable "SEREDIP" as the dependent variable and the measured variables Y2KEFFORT, ORGSP, and ORGHM as the independent variables. The null hypothesis was not rejected indicating that among the companies surveyed, the occurrences of serendipitous events were not statistically significant. However, the literature indicated that serendipitous events have occurred, although these occurrences were not universal.
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Hassebroek, Pamela Burns. "Institutionalized Environments and Information Security Management: Learning from Y2K." Diss., Available online, Georgia Institute of Technology, 2007, 2007. http://etd.gatech.edu/theses/available/etd-06192007-111256/.
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Thesis (Ph. D.)--Public Policy, Georgia Institute of Technology, 2008.Rogers, Juan D., Committee Chair ; Klein, Hans K., Committee Member ; Bolter, Jay David, Committee Member ; Nelson-Palmer, Mike, Committee Member ; Kingsley, Gordon, Committee Member.
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Leong, Ming Haw. "Prolonging the deadline of Y2K using non-printable EBCDIC characters." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape3/PQDD_0022/MQ62134.pdf.
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Azad, Roya. "A belief network for prediction of extra cash withdrawals for Y2K." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0019/MQ54102.pdf.
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Claflin, Ray III. "Y2K AND GPS WNRO: A FITTING FINALE TO THE SECOND MILLENNIUM." International Foundation for Telemetering, 2000. http://hdl.handle.net/10150/608277.
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International Telemetering Conference Proceedings / October 23-26, 2000 / Town & Country Hotel and Conference Center, San Diego, CaliforniaThis paper discusses the successful passage past the Year 2000 (Y2K) Rollover and GPS 1999 (Week Number Roll Over) WNRO. The reasons the glitches seen at those events were relatively minor and the lessons learned to help enter the Third Millennium with careful optimism are reviewed.
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Adams, Ami Rhae. "Notes on a non-event: Y2K as social construction and its discontents." Thesis, The University of Arizona, 2001. http://hdl.handle.net/10150/291533.
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In the late 1990s, a 30-year-old decision by computer programmers was translated into "Y2K," a problem that threatened the technological and social infrastructure of contemporary Western society. This work examines that translation from the dominant perspective and juxtaposes it to the experiences of people who believed Y2K was real. In contrast to "mainstream" views that ultimately saw Y2K as a "non-event," these individuals constructed and experienced Y2K as an event with significant impact on their lives. In the dominant view, Y2K was understood through the lens of technology; when the technological failure markers that came to define Y2K in this construction did not materialize, Y2K became a non-event. For believers, who used a different set of markers, Y2K retained significance. This work demonstrates the importance of examining alternate perspectives on events, by showing that Y2K was only a non-event in its dominant construction.
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Claflin, Ray III. "Calendars and Current Calendar Issues: Year 2000 and GPS 1999 Week Number Roll Over." International Foundation for Telemetering, 1998. http://hdl.handle.net/10150/609224.
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International Telemetering Conference Proceedings / October 26-29, 1998 / Town & Country Resort Hotel and Convention Center, San Diego, CaliforniaThis paper will present a selected overview of calendars and calendar development from antiquity to the current Gregorian calendar. The current hot topics of the GPS 1999 Rollover and the Year 2000 Millennium Rollover will be explained.
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Gustavson, Sandra Ruth. "Organizational Learning in Response to Large Scale Events." Kent State University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=kent1208717590.
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Booth, Judith, and edu au jillj@deakin edu au mikewood@deakin edu au kimg@deakin. "A critique of "cultural fit" in relation to the recruitment of Indian Information Technologists for the Y2K project in Australia." Deakin University. School of Communication & Creative Arts, 2002. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20040617.142627.
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In this study of intercultural communication, I investigate the multi-faceted meaning of the expression " cultural fit " in the sense that it is used by recruiters when shortlisting Indian information technologists to fill skills shortages for the Y2K project in Australia. The data is in the form of ten videotaped interviews in Bangalore and the recruiter commentary on those tapes in Melbourne. A crucial decision to be made by recruiters in any shortlisting process is " How will the candidate fit into the workplace?" This question becomes more problematical when applied to overseas-trained professionals. I take a critical approach, drawing principally on the research traditions of linguistics where studies of intercultural communication and workplace interaction intersect, employing chiefly the tools of Critical Discourse Analysis and Interactional Sociolinguistics and the more abstract notions of Bourdieu. A bridge between these different discourse approaches is provided by Sarangi & Roberts < 1999 < who show the connection between the larger institutional order and interactional routines, through an elaboration of frontstage talk and backstage talk following Goffman < 1959 < .
An analysis of the interviews < frontstage talk < reveals "cultural fit" to involve a knowledge of institutional talk, in particular, directness. The recruiter commentary < backstage talk < draws attention to issues of intelligibility, body language, technical expertise and workplace values. the study shows that Indian Information Technologists have "partial fit" in that they possess technical fit but do not demonstrate, or lack the opportunity to demonstrate in the interview, Australian workplace values such as small talk, humour and informality. The recruiter judgments were fleeting and apart from checking for intelligibility, were made on the basis of candidates' body language thus highlighting its importance and its relative absence from the discourse approaches mentioned above. This study shows clearly that there is room for more communicative flexibility on the part of all the stakeholders.
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Quigley, K. F. "Y2K as a lens on risk regulation regimes in the US and Uk governments : the Hood, Rothstein and Baldwin (2001) framework." Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426985.
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Claflin, Ray III. "CURRENT TIME SCALES AND CHALLENGES: GPS 1999 WNRO AND THE YEAR 2000." International Foundation for Telemetering, 1999. http://hdl.handle.net/10150/608442.
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International Telemetering Conference Proceedings / October 25-28, 1999 / Riviera Hotel and Convention Center, Las Vegas, NevadaThis paper describes the current internationally recognized atomic time scales of International Atomic Time (TAI), Coordinated Universal Time (UTC), and Global Positioning System (GPS) Time as well as solar based Universal Time. The concept of Leap Seconds and the differences between the time scales are discussed. A brief history of the international agreements that created organizations responsible for maintaining these time scales is provided. A brief review of the GPS 1999 (Week Number Roll Over) WNRO with its potential GPS user problems is provided. Prudent personal precautions are proposed for the Year 2000 (Y2K) Rollover.
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Fent, Darla. "An Examination Of The Variation In Information Systems Project Cost Estimates: The Case Of Year 2000 Compliance Projects." Thesis, University of North Texas, 2000. https://digital.library.unt.edu/ark:/67531/metadc2535/.
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The year 2000 (Y2K) problem presented a fortuitous opportunity to explore the relationship between estimated costs of software projects and five cost influence dimensions described by the Year 2000 Enterprise Cost Model (Kappelman, et al., 1998) -- organization, problem, solution, resources, and stage of completion. This research was a field study survey of (Y2K) project managers in industry, government, and education and part of a joint project that began in 1996 between the University of North Texas and the Y2K Working Group of the Society for Information Management (SIM).
Evidence was found to support relationships between estimated costs and organization, problem, resources, and project stage but not for the solution dimension. Project stage appears to moderate the relationships for organization, particularly IS practices, and resources. A history of superior IS practices appears to mean lower estimated costs, especially for projects in larger IS organizations. Acquiring resources, especially external skills, appears to increase costs. Moreover, projects apparently have many individual differences, many related to size and to project stage, and their influences on costs appear to be at the sub-dimension or even the individual variable level. A Revised Year 2000 Enterprise Model is presented incorporating this granularity.
Two primary conclusions can be drawn from this research: (1) large software projects are very complex and thus cost estimating is also; and (2) the devil of cost estimating is in the details of knowing which of the many possible variables are the important ones for each particular enterprise and project. This points to the importance of organizations keeping software project metrics and the historical calibration of cost-estimating practices. Project managers must understand the relevant details and their interaction and importance in order to successfully develop a cost estimate for a particular project, even when rational cost models are used. This research also indicates that software cost estimating has political as well as rational influences at play.
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Grunewald, Riedel, Schier, and Schletter. "Mitteilungen des URZ 1/1999." Universitätsbibliothek Chemnitz, 1999. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-199900199.
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Wolf, L., F. Richter, A. Heik, R. Meyer, M. Ehrig, G. Heide, G. Fischer, et al. "Produktive und sichere Netzanwendungen." Universitätsbibliothek Chemnitz, 1999. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-199900373.
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Wolf, L., F. Richter, A. Heik, R. Meyer, M. Ehrig, G. Heide, G. Fischer, et al. "Produktive und sichere Netzanwendungen." Technische Universität Chemnitz, 1999. https://monarch.qucosa.de/id/qucosa%3A17559.
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Keudel, Johannes. "Untersuchung der lauftechnischen Potentiale von LEILA- gegenüber Y25-Güterwagendrehgestell." Aachen Shaker, 2008. http://d-nb.info/991851323/04.
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Rozenberg, Sebastian. "Concepts of Digital Objects : Digital Records and the Relational Objects of Yuk Hui." Thesis, Mittuniversitetet, Institutionen för informationssystem och –teknologi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-39348.
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The writings of Yuk Hui, bringing together technical and philosophical insights, provides new theory for the digital, something desired by many in archival research. The aim of this study is to assess the use of Hui’s theories on digital objects and web ontologies as a unifying theory for archival studies, looking at the concept of digital records in particular. Two types of ontology are needed in order to understand digital objects according to Hui: (1) ontologies which relates to the technical language and hierarchies of knowledge representation, like metadata; (2) Ontology, which is the question of Being in the tradition of Heidegger’s phenomenology, the understanding of what it is to be in the world. Both of these ontologies are needed to account for the nature of the digital object. Further, digital objects are produced and constituted through their relations, which can be divided into discursive (technical and logical) and existential (the understanding of being in the world) relations. Digital objects must be approached both as technical formal entities, and as beings in the world. The first register is common, the second – more existential approach – is rarely applied. Using a metatheoretical and hermeneutic method, different conceptions of digital records are discussed, in order to find commonalities and possibilities in relation to Hui’s theory. The digital record as: a process of becoming, information as affordance, context, temporality and evidence are all related to and structured through the application of Hui’s perspective. The thesis ends with the contribution of a possible redefinition of digital records: A digital record is constituted and concretised as material by discursive and existential relations, that taken together function as a persistent representation. Further, Hui’s digital object theory is suggested as a structuring and unifying theory. In relation to digital records Hui’s theory on digital objects can function as a metatheoretical measure, and a method of critical reading.Yuk Hui för samman tekniska och filosofiska perspektiv och erbjuder ny teori för det digitala, något som ofta efterfrågas inom arkivvetenskapen. Syftet med denna studie är att applicera Huis teori om digitala objekt och webontologier som en förenande teori för arkivstudier, specifikt i förhållandet till konceptet digitala records. Två typer av ontologi behövs för att förstå digitala objekt enligt Hui: (1) ontologier som relaterar till tekniskt språk och hierarkiska kunskapsrepresentationer, så som metadata; (2) Ontologi som frågan om varat i fenomenologen Martin Heideggers bemärkelse; förståelsen av vad det är att vara i världen. Båda dessa ontologier behövs för att redogöra för det digitala objektets natur. Vidare produceras och konstitueras digitala objekt genom sina relationer, som kan delas upp i diskursiva (tekniska och logiska) och existentiella (förståelsen av att vara i världen) relationer. Digitala objekt måste förstås både som tekniska formella entiteter och som varelser i världen. Det första perspektivet är vanligt förekommande medan det andra – mer existentiella förhållningssättet – sällan tillämpas. Med hjälp av en metateoretisk och hermeneutisk metod diskuteras olika föreställningar om digitala records för att hitta likheter och möjligheter i relation till Huis teori. Digitala records som: en process av tillblivande, information som affordance, kontext, temporalitet och bevis är koncept som relateras och struktureras genom tillämpningen av Huis perspektiv. Uppsatsen bidrar med en möjlig omdefinition av digitala records: Ett digitalt record konstitueras och konkretiseras som materiellt genom diskursiva och existentiella relationer vilka, tillsammans, fungerar som en ihållande representation. Vidare framhålls Huis teori för digitala objekt som en strukturerande och förenande teori. I relation till digitala records kan Huis teori om digitala objekt fungera som ett metatoretiskt mått och en metod för kritisk läsning.
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Pereira, Isabel Veloso Alves. "Efeito do Yo Jyo Hen Shi Ko (YHK) no metabolismo lipídico na esteatohepatite experimental." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5147/tde-21062010-174627/.
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A Doença Hepática Gordurosa Não Alcoólica (DHGNA) é atualmente uma das formas mais comuns de doença hepática, e está diretamente relacionada com a obesidade. Estudos indicam uma prevalência por volta de 30% na população ocidental e 11% na população oriental. A DGHNA possui um largo espectro abrangendo desde casos de esteatose simples sem inflamação, até casos com esteatohepatite e fibrose, podendo evoluir para cirrose e carcinoma hepatocelular. A fisiopatogênese da DHGNA é baseada em múltiplos eventos: resistência insulínica, aumento da lipólise periférica, aumento da síntese de novo de lipídeos, estresse oxidativo, endotoxemia crônica no desencadeamento da inflamação e fibrose entre outros. A etapa inicial caracteriza-se pelo acúmulo de ácidos graxos no hepatócito, suplantando sua capacidade de metabolização e exportação conseqüente à ação lipogênica da insulina, desta forma o metabolismo de ácidos graxos está intimamente ligado ao desenvolvimento da DHGNA. O Yo Jyo Hen Shi Ko (YHK) é um composto natural usado na medicina japonesa para tratamento de doenças hepáticas e apresenta propriedades antioxidantes, antiinflamatórias e hipolipemiantes. O presente estudo teve como objetivo avaliar o efeito do YHK no metabolismo hepático de lipídeos. Para tanto, foram utilizados camundongos obesos (ob/ob) com esteatohepatite não alcoólica (ENA) induzida por dieta deficiente em colina e metionina (DCM) e foram analisados no tecido hepático, genes relacionados com a síntese de novo de lipídeos (SREBP1c, FASn), genes relacionados com a oxidação e exportação de lipídeos (CPT1a e SCD-1, MTP), assim como genes relacionados com o armazenamento de lipídeos (Perilipina e ADFP). O YHK apresentou um efeito citoprotetor hepático com melhora dos parâmetros histológicos neste modelo experimental de ENA. Associadamente, houve redução na expressão de genes relacionados à síntese de novo como SREBP e da FASn, quando se comparou o grupo tratado com DCM+YHK com o grupo não tratado DCM. Em contrapartida, houve aumento na expressão da MTP e da SCD-1 ocasionando uma maior exportação de triglicerídeos hepáticos nos animais que utilizaram o YHK. Ainda, o YHK modulou as proteínas Perilipina e ADFP. Por outro lado, não houve modificação na oxidação de lipídeos.. Conclui-se que o YHK pode ser uma droga promissora no tratamento da DHGNA, já que age modulando genes envolvidos na síntese e exportação de lipídeos hepáticos, reduzindo o acúmulo de gordura no hepatócitoNonalcoholic fatty liver disease (NAFLD) is currently one of the most common forms of liver disease, related directly to the increase of obesity in the world. Previous studies indicate a prevalence of around 30% in the western population and 11% in the eastern. This disease covers cases from simple steatosis without inflammation to cases of steato hepatitis (NASH) and fibrosis and it may lead to liver cirrhosis and hepatocellular carcinoma. The pathophysiology of NAFLD is based on multiple events: insulin resistance, increased peripheral lipolysis, increased de novo lipogenesis, oxidative stress, endotoxemia in triggering chronic inflammation and fibrosis and others. The initial stage of the disease is characterized by the accumulation of fatty acids in hepatocytes caused by the lipogenic action of insulin. This condition results in the surpassing of the cells ability to metabolize and export. This way, the metabolism of fatty acids is closely linked to the development of NAFLD. The Yo Jyo Hen Shi Ko (YHK) is a natural compound used in Japanese medicine for the treatment of liver disease and it has antioxidant, anti-inflammatory and lipid lowering properties. This study aimed to evaluate the effect of YHK in the hepatic metabolism of lipids. An experimental model was designed using obese mice (ob/ob) affected by NASH induced by a deficient diet in choline and methionine (MCD). Then, genes from its hepatic tissue related to de novo lipogenesis (SREBP1c, FASN), to lipid oxidation and exportation (CPT1A and SCD-1, MTP) as well as genes related to lipid storage (Perilipin and ADFP) were analyzed. The YHK presented a cytoprotective effect, improving the hepatic histological parameters in this experimental model. Additionally, when comparing the group treated with MCD + YHK (diet + YHK) to the untreated MCD group (diet) there was a reduction in the expression of genes related to de novo synthesis like SREBP1c and FASn. However, an increased expression of MTP and SCD-1 were observed leading to a greater liver exportation of fatty acids in animals that were treated with YHK. Moreover, the YHK modulated the proteins Perilipin and ADFP. On the other hand, there was no changing in lipid oxidation. In summary, the YHK can be a promising drug for the treatment of NAFLD, as it acts by modulating genes involved in the synthesis and exportation of hepatic lipids, reducing the accumulation of fat in hepatocytes
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Viljoen, Louise. "Breyten Breytenbach se (`yk') : 'n semiotiese ondersoek." Thesis, Stellenbosch : Stellenbosch University, 1988. http://hdl.handle.net/10019.1/70129.
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Ma, Yik Ki [Verfasser]. "New Insights into the Milky Way Magnetic Fields through Radio Broadband Spectro-polarimetry / Yik Ki Ma." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/1207923508/34.
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Quella, Mark A. "Developing a training manual for the Y2 system." Menomonie, WI : University of Wisconsin--Stout, 2005. http://www.uwstout.edu/lib/thesis/2005/2005quellam.pdf.
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Lubini, Greice. "NtCDKG;2, uma proteína multifuncional, relacionada aos processos de transcrição, processamento de RNA e organização do fuso acromático no ciclo celular de Nicotiana tabacum." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-06062017-171202/.
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Os estudos em reprodução e desenvolvimento das plantas, especialmente voltados ao pistilo, são de grande interesse agronômico, econômico e científico. Em nosso laboratório, recentemente, foi identificado e caracterizado SCI1 (Stigma/style Cell-cycle Inhibitor 1), um inibidor do ciclo celular que atua de forma tecido específica no pistilo de Nicotiana tabacum L. e Arabidopsis thaliana (L.) Heynh. (DEPAOLI et al., 2011; DEPAOLI; DORNELAS; GOLDMAN, 2014). Foi identificada a proteína NtCDKG;2 (N. tabacum Cyclin-dependent Kinase 2) como parceira de interação de NtSCI1 (N . tabacum SCI1), em um ensaio de pull-down (STRINI, 2014). A literatura aponta que os inibidores de ciclo celular regulam o ciclo através da inibição de CDK, o que sugere que NtSCI1 possa regular o ciclo celular através da inibição de NtCDKG;2. O presente estudo mostra análises detalhadas da localização de GFP-NtCDKG;2 em células epiteliais de N. benthamiana. Verificou-se que a proteína NtCDKG;2 está presente no nucleoplasma e também co-localiza em speckles nucleares. Em cultura de células BY2 expressando GFP-NtCDKG;2 de forma estável, foi observado que, durante a metáfase e anáfase, a proteína NtCDKG;2 está junto ao fuso acromático. Adicionalmente, ensaios de BiFC (Bi-molecular Fluorescence Complementation) realizados neste trabalho mostram que a interação entre as proteínas NtCDKG;2 e NtSCI1 ocorre em uma região localizada na periferia nucleolar, durante a interfase. Também foram identificadas possíveis isoformas de NtCDKG;2. A possibilidade da ocorrência de isoformas sugere que, de maneira análoga à sua homóloga em humanos, as isoformas resultantes de NtCDKG;2 possam atuar em diferentes processos. Em busca de parceiros de interação de NtCDKG;2, para identificar em que vias esta proteína atua, foi realizado um screening de uma biblioteca de cDNAs de estigmas e estiletes de N. tabacum, no sistema de duplo-híbrido em leveduras (Y2H). Através desse ensaio, foram identificados diversos parceiros envolvidos com transcrição e processamento de RNA. Dentre as proteínas identificadas, cuja interação foi confirmada neste trabalho, destaca-se a proteína NtCDKF;1, uma proteína que fosforila o CTD da RNA Polimerase II e, dessa forma, auxilia a transcrição e o splicing cotranscricional (HAJHEIDARI et al., 2012). O presente trabalho mostra também a interação entre NtCDKG;2 e a proteína NtCBP1, uma proteína que possui um papel importante na regulação inicial da transcrição de proteínas mediadoras do crescimento do tubo polínico (LI et al., 2015). xx Adicionalmente, o screening de Y2H possibilitou a identificação da interação entre NtCDKG;2 e NtRanBP1, uma proteína chave na formação do fuso acromático que, em humanos, interage com uma isoforma homóloga a NtCDKG;2, a CDK11p46 (MIKOLAJCZYK et al., 2003; YOKOYAMA et al., 2008; ZHANG; DAWE, 2011). Análises in silico realizadas com a sequência de aminoácidos de NtCDKG;2 apontaram motivos de interação com proteína do tipo F-Box, ciclina, CDK, fosfatase, 14-3-3, BRCA1 e indicaram o local provável de interação do complexo CDK-Ciclina com o respectivo inibidor. Foi testada e comprovada a interação entre NtCDKG;2 e a 14-3-3D, por Y2H, uma parceira de NtSCI1. Outra lacuna que precisava ser preenchida é referente à regulação da expressão de NtSCI1. Com este intuito, foram realizadas análises in silico para identificar elementos cis-regulatórios na sequência genômica de NtSCI1. Essas análises indicaram a presença de importantes elementos cis-regulatórios relacionados à identidade meristemática (como WUSCHEL e AINTEGUMENTA), identidade do carpelo (AGAMOUS, BELL) e progressão do ciclo celular (E2F e CDC5). Algumas considerações podem ser feitas associando os resultados obtidos a estudos feitos paralelamente em nosso laboratório: 1) Compilando a localização de NtCDKG;2 em splicing speckles e sua interação com os diferentes parceiros de interação relacionados à transcrição e splicing, sugere-se que NtCDKG;2 também atue nos processos transcricionais e de splicing. 2) Considerando a localização subcelular de NtCDKG;2 durante as diferentes fases do ciclo celular, às análises in silico dessa proteína que identificaram sua possível interação com BRCA1, além da interação confirmada com a proteína NtRanBP1, é possível sugerir que NtCDKG;2 atue, direta ou indiretamente, na organização do fuso acromático de plantas. 3) Propõem-se que NtSCI1 regule a proliferação celular no pistilo através da interação com NtCDKG;2 que se dá no nucléolo das células. Dessa forma, NtSCI1 prenderia NtCDKG;2 no nucléolo e inibiria sua atuação, como na organização do fuso acromático, o que acarretaria inibição da divisão celular. 4) Devido aos motivos cis-regulatórios encontrados na sequência genômica de NtSCI1 e o efeito que a proteína possui desde as fases iniciais do desenvolvimento do pistilo, sugere-se que a expressão desse gene seja regulada por elementos diretamente envolvidos no controle do término do meristema floral e nas vias de desenvolvimento de órgãos florais.Studies on plant reproduction and development, specifically those related to the pistil, are of great agronomic, economic and scientific interest. In our laboratory, we recently identified and characterized SCI1 (Stigma/style Cell-cycle Inhibitor 1), an inhibitor of the cell cycle which acts tissuespecifically in the pistil of Nicotiana tabacum L. and Arabidopsis thaliana (L.) Heynh. (DEPAOLI et al., 2011; DEPAOLI; DORNELAS; GOLDMAN, 2014). The NtCDKG;2 (N. tabacum Cyclin-dependent Kinase G; 2) protein was identified as an interaction partner of NtSCI1 (N. tabacum SCI1) in a pulldown assay (STRINI, 2014). The literature suggests that cell cycle inhibitors control the cycle through the inhibition of CDKs, indicating that NtSCI1 might control cell cycle by inhibiting NtCDKG;2. This study shows detailed analysis of GFP-NtCDKG;2 localization in leaf cells of N. benthamiana. The analysis shows that NtCDKG;2 is present in the nucleoplasm and also co-localizes with nuclear speckles. In BY2 cell culture stably expressing GFP-NtCDKG;2, it was observed that NtCDKG;2 is at the achromatic spindle during metaphase and anaphase. Additionally, BiFC (Bimolecular Fluorescence Complementation) assays performed in this study have shown that the interaction of NtCDKG;2 and NtSCI1 occurs in the nucleolar periphery during interphase. Putative isoforms of NtCDKG;2 were also identified. The possible occurrence of these isoforms suggests that, in a similar way to its human homologue, NtCDKG;2 putative isoforms could act in different processes. To identify in which processes this protein could act, a search for NtCDKG;2 interaction partners was performed through the screening of a N. tabacum stigma and style cDNA library in the yeast two-hybrid (Y2H) system. Several partners identified through this assay have roles in RNA transcription and processing. Among the identified partners with interaction confirmed during this work, stands out the NtCDKF;1 protein, a CDK that phosphorylates the RNA polymerase II CTD, and thus, supports transcription and co-transcriptional splicing (HAJHEIDARI et al., 2012). This study also shows the interaction of NtCDKG;2 with NtCBP1, a protein which has an important role in the transcriptional regulation of genes encoding proteins mediating pollen tube growth (LI et al., 2015). Furthermore, the Y2H screening allowed the identification of the interaction of NtCDKG;2 with NtRanBP1, a key protein in the formation of the achromatic spindle which, in humans, interacts with the CDK11p46 isoform (MIKOLAJCZYK xxii et al., 2003; YOKOYAMA et al., 2008; ZHANG; DAWE, 2011), a homologue of NtCDKG;2. In silico analysis of the amino acid sequence of NtCDKG;2 revealed motifs of predicted interaction with F-box proteins, cyclins, CDKs, phosphatases, 14-3-3s, BRCA1, and also pointed the region where the CDK-cyclin complex might interact with its respective inhibitor. The interaction of NtCDKG;2 with 14-3-3D, a known partner of NtSCI1, was tested and confirmed by Y2H. Another gap that needed to be filled is related to the regulation of NtSCI1 expression. To address this issue, in silico analysis to identify cis-regulatory elements was performed in NtSCI1 genomic region. These analyses revealed the presence of important cis-regulatory elements related to meristem identity (such as WUSCHEL and AINTEGUMENTA), carpel identity (AGAMOUS, BELL), and cell cycle progression (E2F and CDC5). Taken together results from this study and parallel studies performed in our laboratory, a few remarks can be made: 1) Taken the localization of NtCDKG;2 in splicing speckles, and its interaction with different proteins involved in transcription and splicing, it is suggested that NtCDKG;2 also has roles on these processes; 2) Considering the subcellular localization of NtCDKG;2 during the different cell cycle phases, the in silico analysis of this protein that predicts its interaction with BRCA1, and the confirmed interaction with NtRanBP1 protein, it is possible to suggest that NtCDKG;2 has a direct or indirect role in the organization of the achromatic spindle in plants; 3) It is proposed that NtSCI1 regulates cell proliferation in the pistil through its interaction with NtCDKG;2, which occurs in the nucleolus. Thus, NtSCI1 could hold NtCDKG;2 in the nucleolus, inhibiting its actions, such as in the organization of the achromatic spindle, resulting in cell division arrest. 4) Due to the cis-regulatory elements found in the genomic sequence of NtSCI1, and the effect of this protein since the initial stages of pistil development, it is suggested that its expression is regulated by elements directly involved in the control of the floral meristem termination and pathways of floral organ development.
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Wong, Yuk Lung [Verfasser]. "Untersuchungen zur intestinalen Verträglichkeit von Hydroxyethylstärke: Etablierung und Validierung eines neuen isoliert perfundierten Mausdünndarm-Modells / Yuk Lung Wong." Kiel : Universitätsbibliothek Kiel, 2014. http://d-nb.info/1052893694/34.
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Sabbagh, Cyrus Raja Rubenstein. "Towards a global interactomic map between the Ralstonia solanacearum species complex core type III effectors and the tomato proteome." Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30217.
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La stratégie de virulence du complexe d'espèces Ralstonia solanacearum (RSSC) repose sur des effecteurs de type III (T3E) injectés à l'intérieur des cellules végétales via un système de sécrétion de type III. Grâce aux séquences génomiques actuellement connues de plus de 150 souches phytopathogènes du RSSC, nous avons identifié différents ensembles de core-T3E selon qu'ils sont conservés parmi toutes les souches du RSSC ou dans des souches isolées à partir d'hôtes spécifiques. Comme ces core-T3E ont été conservés au sein des souches de RSSC affectant les Solanacées, nous émettons l'hypothèse que ces déterminants doivent être importants pour la virulence. Notre objectif principal est d'identifier les cibles putatives chez la tomate pour tous ces core-T3E en utilisant des criblages systématiques par double hybride sur une banque d'ADNc de racines de tomate. De nombreuses cibles pour la tomate, dont certaines sont des ‘‘hubs’’, ont été identifiées à partir de 14 criblages. Par des approches de double hybride matriciel, nous avons confirmé et étendu le nombre de cible ‘’hub’’ à 17 candidats. La validation de certaines interactions in planta ainsi que la génétique de ces "hubs" sont poursuivies pour tester leur contribution au flétrissement bactérien. Des plantes de tomates CRISPR-Cas9 ont également été réalisés pour valider le rôle de certains de ces gènesThe Ralstonia solanacearum species complex (RSSC) virulence strategy relies on type III effectors (T3Es) injected inside the plant cells via a type III secretion system. Thanks to the currently known genomic sequences of more than 150 phytopathogenic strains of the RSSC, we have identified different sets of core-T3Es according of being conserved among all the RSSC strains or according to strains isolated from specific hosts. As these core-T3Es have been conserved through the evolution of the RSSC strains affecting Solanaceae, we hypothesize that they must be important for virulence in tomato. Our main objective is to identify putative tomato targets for all of these core-T3Es using systematic Y2H screening against a tomato root cDNA library. Many candidate tomato targets, some of which are “hubs”, were identified from 14 screenings. These identified targets have been tested against all the core-T3Es and other effectors from different pathogens and thanks to the Y2H-pairwise-matrix, we were able to increase the number of the identified hubs up to 17 candidates. Validation of some interactions in planta as well as reverse genetics (insertion mutants in Petunia and Arabidopsis) for these “hubs” is carried on to test their contribution to the bacterial wilt. CRISPR-Cas9 tomato plants were also performed to validate the role of some of these genes
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Tolobekova, Aijan. "Analyse der Tier-Umwelt-Interaktionen bei Yaks (Bos grunniens) im kirgisichen Hochgebirge." Doctoral thesis, Humboldt-Universität zu Berlin, 2019. http://dx.doi.org/10.18452/20571.
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Yaks sind sehr gut an die Umweltbedingungen des kirgisischen Hochgebirges angepasst und sind seit Jahrhunderten ein Bestandteil dieses Ökosystems. Politische und wirtschaftliche Veränderungen haben in den letzten 60 Jahren dazu geführt, dass die Yakbestände in Kirgistan zurückgegangen sind. Seit einigen Jahren gibt es Bestrebungen diese wiederaufzubauen. Dabei müssen die ökologischen Ansprüche der alpinen Landschaft berücksichtigt werden. Das Ziel der Arbeit bestand darin, in einem engen zeitlichen Raster, das Verhalten der Yaks im Herdenverband zu analysieren, die Lebendmasseentwicklung von Yakfärsen im Zusammenhang mit dem saisonalen Einfluss zu untersuchen und den Weideertrag zu schätzen. Dazu wurden im Osten Kirgistans Verhaltensuntersuchungen an 12 Yakkühen durchgeführt sowie die Lebendmasseentwicklung von 20 Yakfärsen analysiert. Für die Analyse der Vegetation wurden 10 Plots genutzt.
Das Habitatsverhalten der Yaks ist von verschiedenen Faktoren abhängig, die vor allem im Zusammenhang mit dem großen Weidegebiet stehen: die Variation im Futterangebot, die geografischen Gegebenheiten sowie die Witterungsverhältnisse. Die Untersuchungen zeigten, dass das Verhalten der Yaks stark durch die Jahreszeiten beeinflusst wird. Das bezieht sich auf die Nutzung von Flächen und Höhenlagen sowie auf das Bewegungsverhalten. Es zeigte sich, dass bestimmte Weideareale permanent stärker frequentiert werden. Die Lokomotion der Yaks ist im Winter stärker ausgeprägt als im Sommer. Die Vegetationsanalyse weist darauf hin, dass Ertrag und Futterwert der Weidepflanzen, eindeutig durch die Höhenlage beeinflusst werden. Die Untersuchungen zur Lebendmasseentwicklung zeigten den gravierenden Einfluss der Jahreszeiten und damit des Futterangebotes auf die Lebendmasseentwicklung der Yakfärsen.
Ein detailliertes Wissen über das Verhalten von Yaks kann dazu beitragen, die Bewirtschaftung von Hochgebirgsweideflächen zu verbessern und vorhandene Ressourcen schonend und nachhaltig zu nutzen.Yaks are very well adapted to the environmental conditions of the Kyrgyz high mountains and have been part of this ecosystem for centuries. Political and economic changes over the past 60 years have led to a decline in yak stocks in Kyrgyzstan. For some years, there have been efforts to rebuild them, to this end the ecological demands of the alpine landscape must be taken into account. Within this context, the objectives of the PhD – thesis were to analyse the behaviour of the yaks in the herd, to investigate the development of the body weight of yak heifers in connection with the seasonal influence and to estimate the grazing yield in a tight time grid. In the eastern part of Kyrgyzstan, 12 yak cows were selected for the behavioural studies and 20 yaks heifers for the development of the body weight. For the analysis of the vegetation, 10 plots were used. The habitat behaviour of the yaks depends on various factors, which are mainly related to the large grazing area: the variation in the forage supply, the different geographical conditions as well as the weather conditions. The investigations showed that the behaviour of the animals is strongly influenced by the seasons, specifically regarding use of areas and altitudes; as well as to exercise behaviour. It was found that certain pastures are permanently more frequented than others. The locomotion of the yaks is more pronounced in winter than in summer. The research on the development of the body weight showed the serious influence of the seasons and thus of the food supply on the development of the yak heifers. Results showed that body growth takes place despite the losses in winter. The vegetation analysis indicates that the yield and feed value of the pasture plants are clearly influenced by the altitude. A detailed knowledge of the behaviour of yaks can help to improve the management of high mountain pastures and thus to use the available resources sparingly and sustainably.
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Pereira, Isabel Veloso Alves. "Efeito do composto natural Yo Jyo Hen Shi Ko (YHK) no ciclo de replicação do vírus da hepatite C (VHC)." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5168/tde-13012015-143326/.
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Estima-se que 170 milhões de pessoas no mundo estejam infectadas com o vírus da hepatite C (VHC), o que está altamente relacionado à ocorrência de hepatite crônica e carcinoma hepatocelular. A prevalência de esteatose hepática em doentes com hepatite C crônica é muito maior do que na população geral variando entre 40 a 75%. A associação entre a infecção pelo VHC e esteatose hepática é multifatorial. Duas formas de esteatose hepática são encontradas em pacientes com hepatite C crônica: esteatose metabólica (fatores de risco) e citopática relacionada ao genótipo 3a. Os lipídios são essenciais para o ciclo de replicação do VHC, eles podem exercer seu efeito em diferentes níveis como: grupos prostéticos em proteínas virais e/ou cofatores celulares na replicação de VHC, componentes especializados na estrutura do VHC onde ocorre a replicação ou como constituinte das partículas lipovirais. Trabalhos experimentais realizados anteriormente por nosso grupo relataram que a administração do composto natural Yo Jyo Hen Shi Ko (YHK) promove a inibição do desenvolvimento da esteatose, redução dos marcadores de estresse oxidativo, menor escore de inflamação, melhora nas concentrações de aminotransferases e diminuição da gordura visceral em um modelo animal de esteato-hepatite não alcoólica. A terapia padrão da hepatite C consiste em uma combinação de interferon peguilado alfa (PEG-IFN-alfa) que estimula o sistema imunológico do hospedeiro para combater a infecção e o composto antiviral ribavirina. Atualmente foram aprovados pelas agências de saúde os inibidores de protease Boceprevir, Telaprevir, Daclatasvir e Simeprevir. No entanto, sua eficiência varia entre os genótipos e as constantes mutações do vírus podem levar a resistência. A falta de uma vacina ou uma terapia definitiva faz com que diversos compostos com diferentes mecanismos de ação sejam testados como possíveis alternativas de tratamento. Tendo em vista a capacidade do YHK de reduzir a esteatose e a importância do metabolismo para a replicação do VHC, o objetivo deste trabalho foi avaliar o efeito do YHK no ciclo celular do VHC. Para isso foram utilizadas técnicas de cultura celular que permitem o estudo das diferenças fases do ciclo de replicação do VHC: entrada (VHCpp), replicação - replicons JFH1-NS3-5B e Con1, replicação e infecção- JC1-Fluc. De forma a elucidar a possibilidade de um único componente da fórmula YHK apresentar efeito sobre o VHC, foram utilizadas para comparação as substâncias ativas de seus ingredientes isoladamente: Panax pseudo ginseng - Notoginsenoside R1; Eucommia ulmoides -(±) Pinoresinol; Licorice root - Ácido Glicirrizínico. Os compostos não apresentaram efeitos na entrada, replicação e liberação de novas partículas virais. Devido à ausência de resultados bem delineados e tendo em vista os resultados das terapias anti-VHC atuais e futuras, é improvável que compostos naturais sejam utilizados ou chegarão ao desenvolvimento clínico nesta indicaçãoWorldwide is estimated that nearly 170 million people are infected with hepatitis C virus (HCV), highly correlated with the occurrence of chronic hepatitis and hepatocellular carcinoma. Hepatitis C patients present higher prevalence of steatosis when compared with the general population, ranging between 40% and 75%. There are two forms of steatosis in HCV infected patients: metabolic steatosis (risk factors) and cytopathic associated with genotype 3. Lipids are essential for the HCV replication cycle. It acts on different functions: as prosthetic groups into viral proteins and / or cellular cofactors in the HCV replication, as specific HCV components or as a constituent of lipovirals particles. Our group previously reported that the administration of the natural compound Yo Jyo Hen Shi Ko (YHK) inhibits steatosis development, decreases markers of oxidative stress and inflammation, improves aminotransferases concentration and decreases the visceral fat. Standard therapy for hepatitis C is a combination of pegylated interferon alpha (PEG-IFN-alfa), stimulating the host immune system to fight infection and the antiviral compound named ribavirin. Nowadays, Telaprevir, Boceprevir, Sofosbovir and Simeprevir are approved as new anti-HCV drugs; they act as protease inhibitors. Its efficiency, however, varies between genotypes, and the constant mutations of the virus can lead to resistance. The lack of vaccines, or a definitive therapy, stimulates the research of new compounds and alternative treatments. In this study, we evaluated the effect of YHK in HCV replication cycle due to the effect of YHK and the importance of lipid metabolism for HCV. For this purpose we used cell culture techniques allowing the study of different stages of HCV replication cycle: entry (HCVpp), replication - replicons JFH1 NS3-5B and Con1, also replication and infection-JC1-Fluc. We also used active compounds of its ingredients: Panax pseudo ginseng - Notoginsenoside R1; eucommia - (±) pinoresinol, Licorice root - Glycyrrhizinic Acid in order to elucidate a possible effect of a single component of the YHK formula in HCV. We could not observe any difference in HCV entry, replication and release in the presence of the four compounds. It is unlikely that natural compounds will be used or come to clinical development in this indication, due to the absence of well defined results and in view of the results of new anti-HCV therapies
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Lima, Vicência Mara Rodrigues de. "Esteato-hepatite não alcoólica (ENA) em camundongos obesos (ob/ob): avaliação do efeito citoprotetor do Yo Jyo Hen Shi Ko (YHK)." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5147/tde-21082007-114419/.
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Introdução: A Doença Hepática Gordurosa Não Alcoólica (DHGNA) tem sido considerada atualmente a forma mais comum de doença hepática no mundo ocidental, relacionada principalmente ao aumento da prevalência da obesidade. A DHGNA abrange um largo espectro de doença, desde casos de esteatose simples até esteato-hepatite (ENA) e fibrose, podendo evoluir para cirrose e carcinoma hepatocelular (CHC). Embora se conheçam os fatores predisponentes para o desenvolvimento da ENA, sua patogênese, assim como tratamento eficaz, permanecem pouco conhecidos. Yo Jyo Hen Shi Ko (YHK), produto derivado do Henshiko, é formado por 4 ingredientes: Panax pseudo ginseng, Eucommia ulmoides, Polygonati rhizoma, e Licorice root. Estes compostos que apresentam propriedades antioxidantes, hepatoprotetoras, hipoglicemiantes e hipolipemiantes. Objetivos: O objetivo deste estudo foi avaliar o efeito do YHK na ENA em camundongos obesos (ob/ob). Métodos: ENA foi induzida em camundongos ob/ob, machos, pesando 40-50g, com 8 semanas de vida, por meio de dieta deficiente em colina e metionina (DCM) ou dieta hiperlipídica (H) durante 4 semanas. Os animais foram distribuídos aleatoriamente por meio de tabela de classificação seqüencial randomizada em 5 grupos, com 5 animais em cada grupo: 1) Grupo DCM: submetidos à dieta em pó, deficiente em colina e metionina por um período de 4 semanas associada a 0,3 mL de solução fisiológica por meio de gavagem diária; 2) Grupo DCM tratado com YHK: submetidos à dieta em pó, deficiente em colina e metionina por um período de 4 semanas associada à solução de YHK (Kyotsu,Yokyo, Japan) (20mg/kg/dia diluída em 0,3mL de solução fisiológica) administrados diariamente por gavagem; 3) Grupo H: submetidos à dieta em pó, hiperlipídica, por 4 semanas associada a 0,3 mL de solução fisiológica diariamente por meio de gavagem; 4) Grupo H tratado com YHK: submetidos à dieta hiperlipídica por um período de 4 semanas associada a solução de YHK (Kyotsu, Yokyo, Japan) (20mg/Kg/dia diluída em 0,3mL solução fisiológica) administrados diariamente por gavagem; 5) Grupo C: submetidos à dieta padrão NUVILAB CR1 (NUVITAL Industria Brasileira Ltda.) por um período de 4 semanas associada a 0,3 mL de solução fisiológica diariamente por meio de gavagem. O diagnóstico histológico de DHGNA e ENA foi determinado segundo a classificação padronizada pelo \"Pathology Committee of the NASH Clinical Research Network\", que designou e validou as características histológicas e um sistema de escore de atividade para DHGNA. Resultados: Os animais das dietas DCM e H não tratados com YHK desenvolveram moderada esteatose macro e microgoticular, balonização hepatocelular e infiltrado inflamatório misto. Com a adição de YHK, ocorreu uma redução na esteatose e inflamação em ambas as dietas. No que se refere à bioquímica hepática, as aminotransferases reduziram-se significativamente em ambos os grupos tratados com o YHK. Associadamente observou-se perda de peso significativa nos camundongos tratados com o YHK em ambas as dietas empregadas (DCM e H) (p<0,05), embora a ingestão alimentar não tenha sido diferente entre os grupos. A redução da ENA e das concentrações de aminotransferases associou-se à redução do estresse oxidativo hepático, avaliado pela diminuição na lipoperoxidação no tecido hepático (redução do MDA - Malonaldeído). Contudo, a glutationa reduzida (GSH) só sofreu redução significativa no grupo da dieta DCM que usou o YHK. Conclusões: Yo Jyo Hen Shi Ko (YHK) inibiu o desenvolvimento da ENA experimental induzida por dieta deficiente em colina e metionina (DCM) e hiperlipídica (H), reduziu as concentrações séricas das aminotransferases e reduziu os parâmetros de estresse oxidativo hepático nesses dois modelos experimentais. Futuros estudos serão necessários para elucidar melhor, o mecanismo de hepatoprotetor do YHK.Background: Oxidative stress plays a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Yo Jyo Hen Shi Ko (YHK) is a complex compound purported to reduce reactive oxygen species (ROS) by blocking the propagation of radical-induced reactions. Aim: The aim of this study was to evaluate the role of the effect of YHK in experimental NASH. Methods: NASH was induced in male ob/ob mice by a high-fat (H) diet or methionine/choline deficient (MCD) diet for 4 weeks. YHK-treated animals received YHK solution orally (20 mg/kg/day) in both experimental diets (n = 5; each group) while control animals received only vehicle. Results: The MCD and H groups developed moderate diffuse macrosteatosis, hepatocellular ballooning, and a diffuse inflammatory infiltrate. With the addition of YHK, there was a marked reduction in macrosteatosis in both groups. This was associated with decreased lipoperoxide and reduced glutathione (GSH) concentrations as well as reduced serum aminotransferases and improved histological markers of inflammation. These changes were also associated with weight loss in the MCD+YHK group and diminished weight gain in the H+YHK group. Conclusion: YHK therapy blunts the development of macrosteatosis in these models of NASH and significantly reduces markers of oxidative stress. YHK also diminishes weight gain in this obesity prone model. Our findings warrant further study on the mechanisms involved with these effects.
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Fällmar, Helena. "Studies of the Neuropeptide Y Receptor Y2 in Human and Zebrafish." Doctoral thesis, Uppsala universitet, Farmakologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-156635.
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The G-protein coupled receptors (GPCRs) comprise the largest family of receptors in humans and other vertebrates. They are embedded in the cell membrane and are activated by many different signaling molecules. Activation modulates cellular signal transduction pathways and influences many physiological processes. Therefore the GPCRs are important as targets for numerous drugs. The receptors for NPY (neuropeptide Y) belong to GPCRs of Class A (rhodopsin-like). NPY and its related peptides PYY and PP are involved in the regulation of appetite, blood pressure and many other processes. They share a common structure and interact with the receptors Y1, Y2, Y4 and Y5 in mammals, and, in addition, Y7 and Y8 in amphibians and bony fishes. This thesis is focused on the human Y2 receptor, known to reduce appetite, by investigating the importance of thirteen amino acid residues for ligand binding. Mutagenesis followed by functional expression and receptor binding was conducted. During the course of this work several new GPCR crystal structures have been resolved, thereby improving the receptor modeling in papers I-III. The major finding is that even though the Y1 and Y2 receptors have evolved from a common ancestor, their points of ligand interaction differ and have thus changed during evolution. In general, the positions investigated resulted in milder changes in the ligands’ affinities for Y2 compared to Y1. These findings were incorporated in the design of new Y1 and Y2 receptor models, leading to improved understanding of how such divergent receptors, sharing only 30 percent sequence identity, can still interact with the same ligands. Notably, several of the mutations introduced in Y2 resulted in increased affinity. A novel NPY receptor gene named Y2-2 was identified in the genomes of zebrafish and medaka. This brings the number of zebrafish NPY receptors to seven. The binding characteristics of zebrafish Y2-2 differed from zebrafish Y2 mainly in the interaction with NPY13-36 and the antagonist BIIE0246. In conclusion, these results increase our understanding of ligand interactions with GPCRs and will be useful for refinement of ligand-receptor models for future development of receptor subtype-selective drugs.
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Jacquemet, Etienne. "La société sherpa à l’ère du « Yak Donald’s » : lutte des places pour l’accès aux ressources dans la région touristique de l’Everest (Népal)." Thesis, Bordeaux 3, 2018. http://www.theses.fr/2018BOR30026/document.
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Au-delà des représentations et des pratiques des alpinistes et trekkeurs, toujours plus nombreux, les conditions du développement et de la pérennisation du système touristique associées à la région népalaise de l’Everest – le Khumbu – semblent de plus en plus reposer sur la valorisation de ressources comme l’eau, l’électricité et l’emplacement foncier. Source de revenus considérables pour les populations locales, et plus particulièrement pour les hébergeurs touristiques, l’accès à ces différentes ressources ne va pourtant pas de soi. Tous les acteurs n’occupent pas les mêmes positions, ni ne possèdent les mêmes moyens pour les valoriser. Cet accès aux ressources, et par extension à de nouvelles positions socio-spatiales, donne lieu à de multiples stratégies fondées sur les capitaux, compétences et intérêts de chacun. Dans cette petite région, néanmoins hautement symbolique, ces stratégies d’accès aboutissent à une lutte des places entre d’une part les membres de la communauté sherpa – qui revendiquent une position d’insiders mais se déploient à l’extérieur du Khumbu par des modes d’habiter très polytopiques –, et d’autre part, de nouvelles populations originaires des basses vallées, en position d’outsiders, qui cherchent à s’y implanter. Dans le contexte d’un espace de plus en plus ouvert sur le monde, en pleine recomposition sociodémographique et culturelle, ce qu’incarne le « Yak Donald’s » – l’un des nombreux nouveaux pubs implantés dans la région –, se pose ainsi la question du partage et de la gouvernance des ressources et des revenus de ce haut-lieu du tourisme. Loin d’être passifs, mais plutôt à l’origine de ces nouvelles dynamiques, cette thèse montre comment les manipulateurs de symboles sherpas contrôlent encore largement le territoire et l’économie du tourismeBeyond the representations and practices of mountaineers and trekkers, conditions for the development and functioning of the touristic system linked to the Nepalese Mount Everest area (the Khumbu region) seem to be increasingly based upon resources such as water, electricity and property. With the rise of tourism, these various resources are source of considerable incomes for local populations, especially for lodge owners. However, sharing these resources is not simple. First, the different actors do not occupy the same positions in relation to them. Second, they don’t have the same capacities (i.e., capital and skills) to exploit them. Eventually, they do not have the same interests depending on their social status, so their cooperation is not always guaranteed. In this small but highly symbolic region, local access to resources leads to “locational struggles” (Lussault, 2009). This struggle opposes members of the Sherpa community - who claim to be deeply rooted inhabitants, but whose ways of life are very polytopic – and on the other hand, new populations from the lower valleys, who seek to establish themselves within the Khumbu region. In the context of intense interrelations with the rest of the world, as well as wide socio-demographic and cultural changes, which is embodied in one of the many new pubs established in the region; the "Yak Donald's", this questions the good resources governance of this tourist hub. Far from being passive, but rather very proactive, this thesis shows how the Sherpas still control the territory and its touristic economy
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黃佩珊 and Pui-shan Helen Wong. "Heterologous expression and immobilization of a haloalkane dehalogenase from Rhodococcus erythropolis Y2." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31226863.
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Wong, Pui-shan Helen. "Heterologous expression and immobilization of a haloalkane dehalogenase from Rhodococcus erythropolis Y2 /." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?
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Nguyen, Viet Luong. "Estimation of biomass for calculating carbon storage and CO2 sequestration using remote sensing technology in Yok Don National Park, Central Highlands of Vietnam." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-99256.
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Global warming and climate change are closely related to the amount of CO2 in the air. Forest ecosystem plays very important role in the global carbon cycle; CO2 from the atmosphere is taken up by vegetation and stored as plant biomass. Therefore, quantifying biomass and carbon sequestration in tropical forests has a significant concern within the United Nations Framework Convention on Climate Change (UNFCC), Kyoto Protocol and Reducing Emission from Deforestation and Forest Degradation (REDD) program for the purpose of the improvement of national carbon accounting as well as for addressing the potential areas for carbon credits, basis for payment for environmental services. The aim of research is to estimate biomass and carbon stocks in tropical forests using remote sensing data for dry forest of central highlands of Vietnam. This result showed that from satellite images of the SPOT, satellites could build the land cover map, carbon map and biomass map of Yok Don National Park, Central Highlands of Vietnam. Through which also the biomass (above ground biomass and below ground biomass) of each type of forest can be calculated. For instance the biomass of the dry forest (Dry Dipterocarp Forest) is 153.49 tones x ha-1, biomass of rich forest is 343.35 tones x ha-1, biomass of medium forest is 210.34 tones x ha-1 and biomass of poor forest & scrub are 33.56 tones x ha-1Sự ấm lên toàn cầu và biến đổi khí hậu có liên quan chặt chẽ với tổng lượng CO2 trong không khí. Hệ sinh thái rừng có vai trò rất quan trọng trong chu trình các bon toàn cầu; khí CO2 trong khí quyển được hấp thụ bởi thảm thực vật dưới dạng sinh khối. Vì vậy, việc xác định sinh khối và carbon tích trữ trong rừng nhiệt đới đã có được sự quan tâm đáng kể trong Công ước của Liên hiệp quốc về biến đổi khí hậu (UNFCC), Nghị định thư Kyoto và Chương trình giảm phát thải từ phá rừng và suy thoái rừng (REDD) gần đây, nhằm cho mục đích cải thiện việc tính toán lượng các bon tích trữ cũng như giải quyết các vấn đề tiềm năng cho tín dụng các bon, làm cơ sở cho việc thanh toán cho các dịch vụ môi trường. Mục đích của nghiên cứu này là ước lượng sinh khối và các bon lưu trữ trong các khu rừng nhiệt đới bằng cách sử dụng dữ liệu viễn thám, mà ở nghiên cứu này là cho rừng khộp Tây Nguyên của Việt Nam. Kết quả cho thấy rằng, từ ảnh vệ tinh SPOT có thể xây dựng bản đồ lớp phủ thực vật, bản đồ các bon và bản độ sinh khối của Vườn quốc gia Yok Đôn, Tây Nguyên Việt Nam. Qua đó đã tính toán được sinh khối (bao gồm cả trên mặt đất và dưới mặt đất) như: đối với sinh khối của rừng khô cây họ dầu (Dry Dipterocarp Forest) là 153,59 tấn/ha, sinh khối rừng giàu là 343,35 tấn/ha, sinh khối rừng trung bình là 210,34 tấn/ha và sinh khối rừng nghèo&cây bụi là 33,56 tấn/ha
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Hassani, Hessameh. "Characterization of NPY receptors Y1, Y2 and Y5 expression and function in vivo /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-737-1/.
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Vanetsev, A. S., I. G. Chuvashova, and O. M. Gaitko. "Preparation of Monodisperse Luminescent Particles of Y2-xGdxO3:Eu by Microwave-assisted Hydrolysis." Thesis, Sumy State University, 2012. http://essuir.sumdu.edu.ua/handle/123456789/34909.
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Development of energy-saving methods of synthesis of monodisperse particles of rare-earth oxides with
improved luminescent properties is very vital task. In present work we’ve developed new method of microwave-assisted synthesis of Y2-xGdxO3:Eu solid solutions, performed a study of influence of Y:Gd ratio on
morphology and luminescent properties of monodisperse oxide particles. We’ve established monotonous
dependence of mean size of particles on Y:Gd ratio. On the other hand dependence of intensity of luminescence on Y:Gd ratio has a clear maximum.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/34909
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Colavito, Luke A. Jr. "High Hill Yak Cheese Production in Nepal: An Analysis of Privatization Policy Incorporating the Impacts of Market Failures for Agro-Industries in Developing Countries." Diss., Virginia Tech, 1997. http://hdl.handle.net/10919/30737.
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In recent years the development community has pressured LDCs to privatize agro- industries. This pressure stems from poor public enterprise performance and an ideological shift. However, public enterprises mitigate market failures. The major objective of this study is to measure the impact of privatizing the Nepalese yak cheese industry. To achieve the objective, public and private behavior are determined. The impacts of privatization stem from changes in monopsony behavior and institutional constraints that differ between the public and private sectors.
The Dairy Development Corporation (DDC) of Nepal produces yak cheese. The DDC's mandate is to provide a "fair" price to consumers and producers. Private producers of cheese have emerged in recent years. Milk shed structures include: single DDC factories, single private factories, multiple private factories, and mixed production.
Market performance is evaluated using partial equilibrium models that include the yak cheese and milk markets. Economic surplus measures are used for evaluation. Herder producer surplus is the most important criterion because herders are the poorest beneficiaries. The impact of privatization is determined through comparison of observed DDC and predicted private equilibria. Private equilibrium is predicted using a simultaneous equation system developed for this research. The equations ensure that supply and demand balance at the aggregate and individual milk shed levels. The Lerner index is incorporated to model monopsony behavior. Private monopsony parameters used in the system are estimated econometrically. A private equilibrium is also predicted with a modified firm cost structure reflecting reduced impacts of institutional constraints.
Findings show that private and public firms are exercising monopsony power. DDC privatization can be advocated because it increases herder producer surplus by 15.4%. Total surplus falls slightly because private cheese is lower quality. DDC privatization decreases herder welfare in milk sheds that support only a single firm. The simultaneous equation system developed to predict the private market equilibrium for post agro-industry privatization has the potential to be extended to solve a broader range of economic problems. The equation system can be adapted to applications where there are multiple production regions and monopsony behavior varies by regional characteristics.Ph. D.
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Yang, Lei. "Structural studies on human dihydroxyacetone kinase (DAK) and the carbohydrate-binding domain of Streptococcus pneumoniae NanA." Thesis, University of St Andrews, 2013. http://hdl.handle.net/10023/4506.
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A number of dihydroxyacetone kinases (DAK) have been described that can utilize either ATP (in animals, plants and some bacteria) or phosphoenolpyruvate (PEP) (in most bacteria) as the energy source to convert dihydroxyacetone (Dha) to dihydroxyacetone phosphate (DhaP), which plays critical roles in many metabolic pathways. It has also been described that Homo sapiens DAK is able to regulate the innate immune system via its interaction with Melanoma differentiation-associated protein 5 (MDA5), which is recognized as an RNA sensor during virus infection. These findings make H. sapiens DAK a very noteworthy research target due to its multiple functions in many fields. Therefore, structural studies of DAK from H. sapiens are presented. The initial structure of the wild type (WT) H. sapiens DAK was determined to 2.5Å resolution and solved by molecular replacement. The structure forms a homodimer and four dimers were shown to be present in each asymmetric unit. However, within each monomer, most regions of the C-terminal domain were disordered, and therefore in order to improve structure quality, multiple site-directed mutagenesis was used. The mutated protein was then crystallized and the structure was determined to 1.4Å. The N-terminal Dha binding domain consists of two α/β regions and the C-terminal ATP binding domain is comprised of eight anti-parallel α-helices, which forms a deep pocket and is filled with a phospholipid molecule. In addition, the structures of mutated DAK in complex with ATP analogues and Dha are also described in the current study. The second part of the project concerned sialidases, which are glycoside hydrolases that specifically hydrolyse terminal sialic acid from various glycans. Streptococcus pneumoniae is one of the most common pathogenic bacteria of humans, and is reported to encode three sialidases that act as virulence factors in bacterial colonization and infection. One of these sialidases, NanA, was reported to be present in all clinical strains and plays a vital role during the bacterial infection. Consequently, the structure of N-terminal Carbohydrate-binding module (CBM) domain of NanA has been determined to 1.8Å, and reveals a β-sandwich fold. The apo form of NanA-CBM is present as a dimer in the asymmetric unit, whereas a monomer was detected when it is bound to sialic acid or its derivatives. Structural comparisons between NanA-CBM and other structures of the CBM40 family were also performed. The substrate binding sites of NanA-CBM forms a cavity that is able to accommodate the substrates. A potential molecular binding site located beside the sialic acid binding site was revealed, and is occupied by the side chain of a lysine from a symmetry- related molecule. Heteronuclear single quantum coherence (HSQC) NMR spectroscopy and fluorescent-based thermal shift assays were also carried out to further characterise the protein. The current results reveal the structure of both DAK from H. sapiens and NanA-CBM from S. pneumoniae, which may contribute to a better understanding towards cell metabolism and bacterial colonization.
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Chen, Rui. "Functional analysis of interactions between influenza A virus protein NS1 and cellular proteins TRBP and PACT." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25717.
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Seasonal and pandemic Influenza virus infections cause about three to five million cases of severe illness and about 250,000 to 500,000 deaths world-wide annually according to the WHO. Although investigated intensively, Influenza virus pathogenesis is still not very well understood and hard to predict. Influenza A viruses contain a segmented, single-(-) stranded RNA genome encoding at least 10 different proteins and are highly diverse due to hypermutation and reassortment. In previous work, 56 viral genes from six different influenza A virus isolates had been cloned and genome-wide screened for virus-host protein interactions using yeast-two hybrid technology and several human and chicken cDNA libraries, leading to the identification of 127 high-confidence cellular interactors of which 40 have also been identified by RNA interference in other studies. In this thesis, two of the cellular interactors identified which both bound to the viral multifunctional protein NS1, TRBP and PACT, were further investigated with regard to their role in virus life cycle. These two proteins are known to be involved in miRNA silencing and PKR regulation. Both interactions between NS1 and TRBP and NS1 and PACT were confirmed by co-immunoprecipitation, and both TRBP and PACT co-localized with NS1 in a cytosolic compartment. NS1 was also found to be present in the RISC complex in pull-down assays with the RISC core component Ago2. In functional assays, NS1 dose-dependently inhibited RNA silencing. Although no differences in TRBP-binding between NS1 proteins of various different influenza strains could be detected in direct mating Y2H assays, they varied with regard to their inhibitory activity on RNA silencing. TRBP and PACT alone were unable to restore NS1-induced inhibition of RNA silencing activity, however both together restored RNA silencing. Moreover, the siRNA knockdown of PACT abolished the association of NS1 with Ago2, and NS1 competitively inhibited the binding of TRBP and PACT to Ago2. The depletion of either TRBP or PACT led to an inhibition of influenza virus replication. The depletion of TRBP also lifted cellular IFNβ level without infection. However, the knockdown of TRBP but not PACT blocked IFNβ production and increased cell viability post infection. These results indicate that NS1 inhibits the binding of PACT and TRBP to the RISC complex and thereby inhibits miRNA-induced gene silencing. The hypothesis that TRBP supports influenza replication potentially by regulating PKR regulation and IFNβ induction requires further investigation. In conclusion, this study provides evidence for the complexity of virus-host interactions and the dual role of viral proteins in activating both positive and negative regulatory cellular mechanisms.
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Feder, Katrin. "Katamnestische Untersuchungen zur suprakondylären und y-kondylären Humerusfraktur im Kindesalter." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/15252.
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Die Arbeit beschäftigt sich mit der suprakondylären und y-kondylären Humerusfraktur im Kindesalter. Die suprakondyläre Humerusfraktur ist die häufigste Ellenbogenfraktur beim Kind, die y-kondyläre Fraktur ist der suprakondylären ähnlich, tritt aber nur selten auf. Es wurden 172 suprakondyläre und 6 y-kondyläre Humerusfrakturen retrospektiv untersucht. Dazu wurden die Daten von 55 ambulant und 123 stationär behandelten Kindern bezüglich Unfallursache, Therapie und Komplikationen ausgewertet. Die Röntgenbilder der stationären Patienten wurden nachbefundet. 32,5% der stationär behandelten Kinder konnten nachuntersucht werden. Die häufigste Unfallursache war ein Sturz aus der Höhe. Im Patientengut waren Frakturen nach Baumann Klassifikation I, II und III zu ähnlichen Teilen vorhanden. Häufigste Behandlungsverfahren waren, ggf. nach geschlossener Reposition, Ruhigstellung in Gipslonguetten oder Blountscher Schlinge, und geschlossene oder offene Reposition und anschließende Fixation mittels Kirschner Drähten. Die häufigsten Komplikationen waren primäre und sekundäre Nervenstörungen, Abweichung der Ellenbogenachse oder Bewegungseinschränkung nach Therapie. 68,5% der nachuntersuchten Patienten hatten ein exzellentes oder gutes Behandlungsergebnis. Die Analyse der Ergebnisse und deren Vergleich mit den Ergebnissen anderer Autoren zeigen Folgendes: Nicht dislozierte Extensionsfrakturen sollten in der Blountschen Schlinge ruhiggestellt werden. Dislozierte Frakturen müssen exakt und schonend, möglichst geschlossen, reponiert werden. Gekreuzte Kirschner Drähte bieten gute Stabilität. Primäre und sekundäre Nervenstörungen haben eine gute Prognose. Radiologische Hilfsmittel wie Baumannwinkel, Rotationsfehlerquotient und Epiphysenachsenwinkel geben nur eine Orientierung bei der Vermeidung von Abweichungen der Ellenbogenachse oder Bewegungseinschränkungen. Y-kondyläre Frakturen mit nur geringer Dislokation der Kondylenfragmente können primär wie suprakondyläre Frakturen behandelt werden.This paper deals with supracondylar and y-condylar humerus fractures in childhood. The supracondylar humerus fracture is the most frequent elbow fracture in children, the y-condylar fracture is similar to the supracondylar one, but occurs only rarely. 172 supracondylar and 6 y-condylar humerus fractures have been analysed retrospectively. For that purpose data of 55 outpatients and 123 in-house treated children have been analysed with regard to the cause of accident, therapy and complications. The radiographs of the in-patients have been revaluated. 32.5% of the in-patients have been seen for follow-up. Most frequent cause of accident was a fall from a height. Within the group of patients, fractures that were classified to Baumann I, II and III occurred to equal rates. The treatments which were used mostly are immobilization in plaster casts or Blount´s loop, after closed reduction if necessary, and closed or open reduction followed by fixation by Kirschner wires. The most frequent complications were primary and secondary nerval disorders, deviation of the axis of the elbow or limitation of elbow function after therapy. 68.5% of the follow-up patients had an excellent or good outcome. The analysis of the results including their comparison to the results of other authors have led to the following conclusion: Nondisplaced extension fractures should be immobilized by Blount`s method. Displaced fractures have to be reduced accurately and sparing, if possible by closed reduction. Crossed Kirschner wires provide a good stability. Primary and secondary nerval disorders have got a good prognosis. Radiological tools like angle of Baumann, rotation error quotient and angle of epiphyseal axis only provide an orientation in avoiding deviation of elbow axis or limitation of elbow function. Y-condylar fractures with only slight dislocation of the condylar fragments can primary be treated like supracondylar fractures.
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Ritter, Zully Maritza. "On the influence of mechanical conditions on osteochondral healing." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2006. http://dx.doi.org/10.18452/15451.
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Im Rahmen der Biomechanik werden der Einfluss mechanischer Bedingungen auf die Heilung biologische Gewebe, wie zum Beispiel Knochen und Knorpeln untersucht. Die vorliegende Arbeit bestimmte zum Einen am Beispiel des Humerus das mechanische Verhalten von intakten und frakturierten Knochen mit verschiedener Knochenqualität (Osteoporose versus gesunden Knochen) unter verschiedenen physiologischen Belastungen. Dazu wurde ein Finite Elemente Modell des entsprechenden Knochens erstellt. Die Knochenqualität erwies sich für die Heilung als wichtigerer Parameter, als die jeweilige physiologische Belastung. Künftige Therapien der Osteoporose sollten daher die jeweils individuelle Dichteverteilung des entsprechenden Knochens explizit berücksichtigen. Zum zweiten wurde ein biphasisches, linear-elastisches Gewebedifferenzierungsmodell entwickelt, mit dem durch iterative Berechnung der Elastizität die Heilung eines osteochondralen Defektes verfolgt werden konnte. Damit konnten die Steifigkeiten und die Orte im und um den ursprünglichen Defekt, an denen sich während der osteochondralen Heilung die verschiedenen Gewebearten neu bilden, quantitativ und qualitativ (Vergleich mit Tierexperimentation) ermittelt werden. Der Erfolg dieses Modells erlaubte die Antwort auf verschiedene Fragestellungen: Einfluß der Defekt- und Gelenkgeometrie auf die Häufigkeit des Auftretens osteochondraler Defekte und ihre Heilungschancen, sowie die Wahl der Steifigkeit eines optimalen Biomaterials zur Defektausfüllung. Osteochondrale Defekte scheinen in konkaver Geometrie etwas besser zu heilen, weil dort mehr hyaliner Knorpel gebildet wird. Grafts mit derselben Steifigkeit des ursprünglichen Knochens bilden kalzifizierenden Knorpel um mehr hyaliner Knorpel am Ende des Heilungsprozesses und sind daher weicheren Biomaterialien vorzuziehen.In biomecanics the influence of mechanical conditions on healing of biological tissues as bones or soft tissues are analysed. In the frame of this work the mechanical behavior of intact and fractured bones with different bone qualities (osteoporotic versus normal) has been examined in a proximal humerus. Therefore a finite element model of the bone was constructed. It was found that the bone quality has a stronger impact on healing than the actual physiological loading condition does. Hence, for a future therapy of osteoporosis the precise density distribution of each individual bone must be considered. In a second step a biphasic, linear-elastic model for tissue differentiation was developed, where osteochondral healing was simulated by iterative calculation of the elastic modulus of Young within the joint region. By using this model it was possible to predict in which order in all regions of the joint the osteochondral healing took place. The stiffnesses of the newly differentiated tissues agreed well to the derived quantities of animal experimentation. Hence, this tissue differentiation model could be used to analyse some questions concerning the geometry and healing success of osteochondral defects. In concave geometry more hyaline cartilage was formed, which has better mechanical properties than fibrous one. Moreover, the stiffness of an optimal biomaterial could be determined: grafts with the same stiffness as the original bone will lead to the formation of calcified bone and more hyaline cartilage, which is favourable compared to a less stiffer biomaterial.
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Tsegmed, Uranchimeg. "Staphylococci isolated from raw milk of yak and cattle in Mongolia : studies on the occurrence, characterization, detection of enterotoxin and antimicrobial susceptibility profile of the isolates /." Uppsala : Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 2006. http://epsilon.slu.se/10186505.pdf.
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SOARES, LEMOS VIRGINIA. "Mecanismes des voies de signalisation des recepteurs de type y2 et y3 au neuropeptide y." Strasbourg 1, 1996. http://www.theses.fr/1996STR15098.
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Yang, Kun. "A conceptual framework for semantic web-based ecommerce." Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23745/23745.pdf.
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Bender, Thorsten Onno. "Untersuchungen zum Effekt von Glukose, Glukosedegradationsprodukten und alternativen osmotischen Agenzien in Peritonealdialyselösungen auf Vitalität und Synthesefunktion peritonealer Mesothelzellen." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/15228.
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Konventionelle hitzesterilisierte, glukosehaltige Peritonealdialyselösungen (PDL) sind aufgrund ihres niedrigen pH-Wertes, ihrer hohen Glukosekonzentration und Osmolalität und ihres Gehaltes an Glukosedegradationsprodukten (GDP) bioinkompatibel. Alternativen zu glukosehaltigen PDL stellen aminosäuren- oder icodextrinhaltige PDL dar. Daneben enthalten auch neuere Glukose-PDL in Doppelkammersystemen aufgrund der Sterilisation von Glukose bei sehr niedrigem pH nur noch sehr geringe GDP-Konzentrationen. In dieser Arbeit wurden die akuten und chronischen Wirkungen verschiedener PDL auf humane peritoneale Mesothelzellen (HPMC) untersucht. Konfluente HPMC wurden mit den zu testenden PDL (glukosehaltige hitze- versus filtersterilisierte und konventionelle versus Doppelkammer-Glukose-PDL, 1% Aminosäuren-PDL und Icodextrin - alle bei neutralem pH-Wert) akut (1-4 Stunden Präinkubation) bzw. chronisch (bis zu 10 Tage) inkubiert. Die Zellvitalität (MTT-Assay) und IL-1beta-stimulierte Sekretion von IL-6 (Zellfunktion) wurden untersucht. Die akute und chronische Exposition von HPMC gegenüber hitzesteriliserten Peritonealdialyselösungen führte zu einer signifkanten Reduktion von Vitalität und Funktion der Zellen. Demgegenüber führte die Inkubation mit filtersteriliserten PDL und GDP-armen PDL zu einer weniger starken Beeinflussung von Vitalität und Funktion. Die aminosäurenhaltige PDL beeinflusste weder akut noch chronisch die Vitalität bzw. Funktion der Zellen negativ. Hingegen unterschied sich die icodextrinhaltige Lösung nicht wesentlich von der hitzesteriliserten PDL mit hohem Glukoseanteil. Die Verringerung des Gehaltes an GDP in PDL mittels Filtersterilisation bzw. alternativer Sterilisation in Zweikammerbeuteln hat einen positiven Einfluss auf Vitalität und Funktion von HPMC in vitro. Der Ersatz des osmotischen Agenz hingegen bedeutet nicht zwansgläufig eine bessere Biokompatibilität.Conventional heat-sterilized glucose-containing peritoneal dialysis fluids (PDF) are bioincompatible due to their acidic pH, high glucose concentration and resulting hyperosmolality, and the presence of glucose degradation products (GDP). Alternatives to these solutions are PDL containing amino acids or icodextrin as the osmotic agent. Furthermore, novel glucose-based PDF contain only trace amounts of GDPs due to the sterilisation of glucose at very low pH in a dual-chamber container system. The present study examines the acute and chronic effects of different PDL on human peritoneal mesothelial cells (HPMC). Confluent HPMC were exposed to the different test PDF (glucose containing heat- versus filter-sterilised PDF and conventional versus dual-chambered glucose PDF, 1% amino-acid PDF and icodextrin – all at neutral pH) in an acute (1-4 hours preincubation) and chronic (up to 10 days) cell culture model. Cell viability (MTT assay) and IL-1beta stimulated IL-6 (cell function) release were assessed. Acute and chronic exposure of HPMC to heat-sterilised PDF resulted in a significant reduction of viability and cell function. In contrast, the incubation of filter-sterilised PDF and dual chambered low GDP solution had only minor effects on cell viability and function. Neither viability nor cell function were negatively affected by the amino-acid PDF following acute and chronic exposure. However, incubation with icodextrin resulted in a similar degree of inhibition as compared to incubation with conventional heat-sterilised glucose PDF. In conclusion, removal of GDP from PDF either via filter-sterilisation or manufacture in dual chambered containers helps to conserve viability and function of HPMC in vitro. However, the replacement of the osmotic agent per se does not necessarily result in improved biocompatibility.
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Wildemann, Britt. "Untersuchung zellulärer Prozesse während der durch Wachstumsfaktoren beeinflussten und unbeeinflussten Frakturheilung." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/13967.
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Im Verlauf der Knochenbildung und Frakturheilung kommt es zu einem Zusammenwirken verschiedener Zell- und Gewebearten. Die beteiligten Zellen unterliegen dabei der Regulation von Wachstumsfaktoren (WF), Zytokinen und Hormonen, die den regelhaften Ablauf kontrollieren und steuernd in Proliferation und Differenzierung von Zellen und deren Matrixsynthese eingreifen. Neben einer optimalen Osteosynthese zur Frakturstabilisation stellt die biologische Beeinflussung der Knochenheilung ein großes Forschungsfeld dar. In Vorarbeiten wurde ein Applikationssystem entwickelt, das mittels einer biodegradierbaren Polymerbeschichtung auf Osteosynthesematerialien die lokale Applikation von WF in biologisch aktiver Form ermöglicht. In vivo wurde an Ratten- und Schweinemodellen erfolgreich die Stimulation der Knochenheilung durch lokal applizierte Wachstumsfaktoren IGF-I, TGF-ß1 und BMP-2 gezeigt. Ziel dieser Arbeit war die Untersuchung zellulärer Prozesse während der beeinflussten und unbeeinflussten Knochenheilung sowie des Effektes der lokalen Applikation von Wachstumsfaktoren von beschichteten Osteosyntheseplatten. Anhand histologischer und immunhistochemischer Untersuchungen, der in situ Hybridisierung an Knochenschnitten und der ELISA-Methode konnte ein früherer Reifungsbeginn des Kallus durch die Wachstumsfaktorenapplikation gezeigt werden, ohne dass es zu Veränderungen der physiologischen Gewebszusammensetzung und der endogenen Wachstumsfaktoren-Expression kam. Durch Zellkulturstudien an primären Osteoblasten und Osteoklasten wurde an isolierten Zelltypen die Wirkung der applizierten WF untersucht und ihr Effekt auf die Zelltypen dargestellt. Die Bildung ektoper Ossifikation im Weichgewebe durch die Wachstumsfaktoren wurde im Schafsmodell ausgeschlossen. Dies stellt einen wichtigen Sicherheitsaspekt beim Einsatz von Wachstumsfaktoren zur Stimulation der Knochenheilung dar. Die lokale Applikation der Wachstumsfaktoren von einer Plattenosteosynthese zur Osteotomiestabilsierung im Rattenmodell zeigte eine signifikante Verbesserung der biomechanischen Stabilität und der Kallusheilung 42 Tage nach Osteotomie Die aus diesen Studien gewonnenen Erkenntnisse liefern Aufschluss zur Weiterentwicklung biologischer Einflussmöglichkeiten auf den Knochenstoffwechsel und die Rolle von WF während der Frakturheilung.In the process of bone formation and healing, different cell- and tissue types are formed. The cells involved are regulated by growth factors (GF), cytokines and hormones, which control the healing and affect the proliferation and differentiation of cells and their matrix synthesis. Besides the use of the optimal osteosynthesis for fracture stabilization, the biological influence of the bone healing represents a large research field. In previous work an application system for local application of GF in biologically active form was developed. In vivo studies revealed a stimulating effect of locally applied IGF-I and TGF-ß1 in a rat and a pig model. Goal of this work was the investigation of cellular processes during the influenced and uninfluenced bone healing. A further aim was the transfer of the local application method to further stabilization systems (plate osteosynthesis). On the basis of the histology, the immunohistology, in situ hybridizing and ELISA methods an earlier beginning of maturing of the callus by the growth factors could be shown, without changes of the physiological callus composition and the endogenous growth factors expression. In further cell culture studies on primary osteoblasts and osteoclasts the effect of the applied growth factors was examined and their effect on the cell types analyzed. The avoidance of ectopic ossification, an important safety aspect with the use of growth factors to stimulate bone healing, was investigated in a sheep model. It was also possible to proof the efficacy of locally applied growth factors delivered extramedullary from plates. The results of these studies provide further explanations for the action of the used growth factors and are necessary for the ongoing development of the application of growth factors for a clinical use.
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Meyer, Henning. "softMip." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2006. http://dx.doi.org/10.18452/15522.
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Bisher sind in der Schnittbildgebung zwei Projektionsverfahren üblich: Die Average-Projektion, die das Bildrauschen gut unterdrückt, jedoch die Kantenschärfe verringert und die Maximum-Intensitäts-Projektion (MIP), deren Bilder sich durch eine gute Kantenschärfe auszeichnen, gleichzeitig aber ein höheres Bildrauschen aufweisen. Daher wurde in der vorliegenden Arbeit eine Synthese beider Verfahren, softMip, mit dem Ziel die jeweiligen Vorteile zu vereinen, entwickelt. In einer Phantom-Studie mit sieben verschiedenen CT-Geräten wurden das Bildrauschen und die Kantenschärfe der drei Projektionsverfahren (MIP, Average und softMip) ermittelt. Anschließend wurden die drei Verfahren in einer klinischen Studie bei der Suche nach Harnwegskonkrementen in 31 ULD-CT-Abdomenaufnahmen eingesetzt. Für jedes Projektionsverfahren wurden sowohl Anzahl, Größe und Lokalisation der Harnwegskonkremente als auch die subjektiven Kriterien Bildrauschen, Kontrast, Konturschärfe, Artefakte und Bildeindruck erhoben. softMip weist im Phantomversuch ein geringeres Bildrauschen als MIP auf (pTwo projection algorithms exist in the cross sectional imaging: Average projection, which features good suppression of image noise, however the edge sharpness diminishes. In maximum-intensity-projection (MIP), images show good edge sharpness, but also amplified image noise. We developed softMip, a synthesis of both algorithms which tries to unite the respective advantages. In a phantom trial on seven different CT-devices, image noise and edge sharpness of the three projection algorithms (MIP, Average and softMip) were aquired. Furthermore image quality of the transition from Average to MIP by means of softMip was compared to the image quality of alpha blending average projection and MIP. In a clinical trial we investigated softMip compared to MIP and average projection in ULDCT examinations of 31 patients with suspected calcifications in the urinary tract. For each projection algorithm amount, size and localization of the calcifications as well as the subjective criteria image noise, contrast, contour sharpness, artifacts and overall image impression were documented. softMip showed a less image noise than a MIP (p
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Jolly, Simmi. "Pharmacological characterisation of selective Y4 and dual Y2/Y4 receptor agonists : novel targets for putative anti-obesity therapies." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/pharmacological-characterisation-of-selective-y4-and-dual-y2y4-receptor-agonists(b9e837b1-e9ca-4bc6-9b85-5b93a7357819).html.
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The GIPIO (Gastrointestinal Peptides in Obesity) collaboration was set up with EU (FP7) funding in 2008, with the aim to develop a series of peptide analogues for the treatment of obesity. Based on the dual Y2/Y4 agonist, Obinepitide ([Q34]hPP), and the Y4 agonist, TM30339 (hPP2-36), novel peptides were developed and subsequently modified by either PEGylation or lipidation to improve their relatively short half-life and pharmacokinetic profile. This thesis presents a detailed study of the in vitro pharmacological data performed to aid the progression of the most promising peptide candidates. An assessment of Y2Y4 potency and activity was made, using optimised Y4 (human colonic epithelial monolayers) and Y2Y4 (human colon mucosae) bioassays, where preparations were mounted in Ussing chambers and changes in short-circuit current (Isc) recorded. In addition, receptor specificity of the most promising agonists was dissected using Y1 and Y2 antagonists. Furthermore, an assessment of Y4 receptor desensitisation was made by application of a subsequent addition of the native hormone, hPP. With a lysine linker at position 30 or 22, chemical modification of Obinepitide with either PEGylation or Palmitoylation resulted in prolonged reductions in Isc in both preparations compared with the transient response seen with their respective predecessors. Increasing the PEG size resulted in greater reductions in Isc, though a PEG22 modification resulted in a loss of functional activity. Mid to long chain lipidation of TM30339 (lauric acid and palmitic acid) also resulted in sustained reductions in Isc. Interestingly, lipidation with a short chain fatty acid (caprylic acid) caused a biphasic response, with an initial transient drop in Isc followed by a sustained anti-secretory response. Importantly, PEG and lipid side chains had no effect upon Isc. Pre-treatment of either human mucosa or epithelial monolayers with PEG2-, or 5-ylated Obinepitide did not cause significant subsequent Y4 desensitisation, an effect that was greater with the larger PEGylated peptide. Contrary to this, long chain lipidated peptides seemed to facilitate rapid and sustained desensitisation, revealed by the loss of further Y4 signalling even after nM lipidated agonist. This divergence in receptor signalling was also observed in fluorescent imaging studies performed by our collaborators. The data presented herein provides the first functional evidence of prolonged activity at the Y2 and Y4 receptors and these modified peptides have the potential to act for longer in vivo as anti-obesity treatments.
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Nowak, Marcel. "Identifizierung neuer MuRF-Multiproteinkomplex assoziierter Proteine." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2014. http://dx.doi.org/10.18452/17008.
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Die Muscle-RING-finger (MuRF) Proteine sind E3-Ubiquitin-Ligasen, die im Muskelgewebe den Ubiquitin-Proteasom-System abhängigen Abbau von Proteinen vermitteln. MuRF1 wird in der Muskelatrophie verstärkt synthetisiert, was zu einem gesteigerten Proteinabbau und damit zum Verlust von Muskelmasse führt. Zudem sind Mäuse, denen MuRF1 fehlt vor Muskelatrophie geschützt. E3-Ubiquitin-Ligasen fungieren oftmals in Multiproteinkomplexen. Dies wurde für MuRF-Proteine bisher nicht gezeigt. Aufgrund dessen sollten neue MuRF-Multiproteinkomplex assoziierte Faktoren mittels Hefe-Zwei-Hybrid-System und SILAC AP-MS identifiziert und deren Einfluss auf die MuRF-Funktion charakterisiert werden. Es wurden sowohl neue als auch publizierte MuRF-Interaktionspartner (Iap) gefunden. Von den neu entdeckten MuRF-Iap wurde der Fokus auf WDR42A gelegt, da das Protein mit beiden Methoden identifiziert wurde und zudem funktionell hoch interessant ist. WDR42A homologe Proteine bilden zirkuläre β-Propeller Strukturen die Multiproteinkomplexe koordinieren. Die Interaktion zwischen MuRF-Proteinen und WDR42A wurde mittels Ko-IP Experimenten und Kolokalisationsstudien bestätigt. Cycloheximid-Abbau-Experimente deuten darauf hin, dass WDR42A kein MuRF1 Substrat-Protein ist. Da die MuRF-Proteine spezifisch im Muskel hergestellt werden, sollte überprüft werden ob WDR42A ebenfalls im Muskelgewebe synthetisiert wird. Es wurde gezeigt, dass WDR42A ubiquitär sowie im Muskelgewebe und in immortalisierten Muskelzellen hergestellt wird. Analog zu MuRF1 wird WDR42A in der Denervations-induzierten Skelettmuskelatrophie und der Muskelentwicklung verstärkt synthetisiert. Die Herunterregulation von WDR42A mittels siRNA in C2C12 Myotuben schützte diese Zellen vor dem Auftreten von Atrophie. Diese Ergebnisse zeigen, dass WDR42A wie MuRF1 an der Entstehung von Muskelatrophie beteiligt ist. Aufgrund der WDR42A Domänenstruktur wird vermutet, dass WDR42A als Scaffolding-Protein MuRF1-Multiproteinkomplexe reguliert.The muscle-RING-finger (MuRF) proteins are E3 ubiquitin ligases which coordinate the ubiquitin-proteasome system dependent protein degradation in muscle tissue. MuRF1 is up-regulated under muscle atrophy conditions. This leads to enhanced proteolysis and thereby to loss of muscle mass and strength. Furthermore are MuRF1 knockout mice resistant to muscle atrophy. E3 ubiquitin ligases often operate in multi-protein complexes. This has not been shown for MuRF proteins. Therefore we used yeast-two-hybrid and SILAC-AP-MS to identify and subsequently characterize new MuRF multi-protein complex associated proteins. We found new and also published MuRF interaction partners (Iap) with both methods. Amongst the new Iap, we focused on WDR42A, because it was found with both techniques and his interesting functional potential. WDR42A exhibits seven consecutive arranged WD40-repeat domains. This domain arrangement leads in homologues proteins to the formation of seven-bladed β-propeller structures, which act as protein interaction platforms that coordinate multi-protein complexes. The protein interaction between the MuRFs and WDR42A was confirmed with Co-IP and co-localization experiments. Cycloheximide decay experiments indicated that WDR42A is not a MuRF1 substrate protein. The MuRF proteins are muscle specific, therefore we tested if WDR42A is also synthetized in muscle tissue. We could show that WDR42A is ubiquitously, but also in muscle tissue as well as in immortalized muscle cells produced. WDR42A is similar to MuRF1 up-regulated under denervation-induced skeletal muscle atrophy as well as in muscle development. Furthermore are C2C12 myotubes resistant to muscle atrophy after siRNA down-regulation of WDR42A. These results demonstrate that WDR42A is like MuRF1 important for the development of muscle atrophy. Due to the domain structure of WDR42A, we hypothesize that WDR42A regulates MuRF1 multi protein complexes as scaffolding protein.
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Mendes, Alessandra Carla. "Estudo estrutural e óptico de pós e filmes do sistema Y23-Al2O3-SiO2 dopados com terras raras para fotônica: síntese via método dos precursores poliméricos e evaporação por feixe de elétrons." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-13122013-113820/.
Full textAbstract:
Com o objetivo de encontrar novas matrizes dopadas com terras raras para aplicação em dispositivos como amplificadores ópticos, o estudo da otimização da emissão dos íons de érbio (Er3+) no sistema Y2O3 Al2O3 SiO2 foi realizado. Pós, cuja composição é dada por (100-x) Y3Al5O12 (x) SiO2 (x varia de 0 a 70, considerando porcentagem em mol) e com concentração fixa de Er2O3 igual a 1% em mol, foram sintetizados via método Pechini modificado e tratados termicamente a 900 e 1000 °C. Espectros de fotoluminescência (FL) na região do infravermelho próximo (transição 4I13/2 4I15/2 dos íons de Er3+) e espectros de up-conversion na região visível (2H11/2 + 4S3/2 + 4F9/2 4I15/2) foram medidos considerando excitação em 980 nm. Técnicas de caracterização como TG, DSC, DRX e FT-IR foram utilizadas para avaliar a cristalização e evolução das fases cristalinas em função da concentração de sílica (x) e da temperatura de tratamento térmico. As análises foram baseadas na comparação entre os dois diferentes solventes usados na preparação das resinas poliméricas: água e etanol. As condições ótimas encontradas para etanol são diferentes das condições encontradas quando água é usada como solvente, confirmando que as propriedades de FL na região do infravermelho próximo são bastante sensíveis às mudanças na estequiometria da matriz e às condições de processamento. A maior intensidade da emissão em 1540 nm foi observada em pós com x = 30 para etanol e x = 70 para água, tratados a 900 e 1000 °C, respectivamente. Este resultado pode estar atribuído à combinação de baixa simetria e boa dispersão dos íons de Er3+ nestas matrizes. Os filmes foram preparados por evaporação por canhão de elétrons (PVD) a partir das pastilhas dos pós estudados. O estudo desses sistemas ainda é pouco reportado na literatura. A caracterização estrutural, morfológica e composicional dos filmes foi considerada com o intuito de avaliar a aplicação destes filmes como guias de ondas amplificadores. Além do elevado índice de refração, estes materiais também podem ser usados em estudos envolvendo efeitos fotoinduzidos.In order to find a new Er-doped host for near infrared (NIR) optical amplifiers, a study on the optimization of the erbium emission ions in the Y2O3 Al2O3 SiO2 system was performed. (100-x) Y3Al5O12 (x) SiO2 powders (x varies from 0 to 70, in mol%) with a fixed Er2O3 concentration of 1.0 mol% were synthesized by a modified Pechini method and heat-treated at 900 and 1000 °C. The photoluminescence (PL) spectra at 1540 nm of the 4I13/2 4I15/2 transition of Er3+ ions and the up-conversion spectra at visible region (2H11/2 + 4S3/2 + 4F9/2 4I15/2) upon 980 nm excitation were evaluated. Different techniques, such as thermogravimetry (TG), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD) and Fourier transform infrared spectroscopy (FT-IR) were considered to evaluate crystallization and phase-evolution of the powders as a function of the silica content (x) and annealing temperature. The analyses were based on the comparison between two different solvents used in the preparation of the polymeric resins: ethanol and water. The optimal conditions for ethanol are quite different than the conditions for water used as solvent, confirming that the PL properties at the NIR region are highly sensitive to the changes in the host stoichiometry and processing conditions. The highest emission intensity at 1540 nm was observed for x= 30 for ethanol and x = 70 for water, treated at 900 and 1000 °C, respectively. This result could be attributed to the combination of low symmetry and good dispersion of the Er3+ ions in these hosts. The films were prepared by electron beam evaporation (PVD) from the pellets of the powders studied. The study of these systems is still little reported in the literature. The structural, morphological and compositional characterization of the films was considered in order to evaluate the application of these films as waveguide amplifiers. In addition to the high refractive index, these materials can also be used in conditions involving photoinduced effects.