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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
281

Evaluation of performance testing tools: Performance Center and BlazeMeter

Maalouf, George Ludwig January 2018 (has links)
The need for performance testing is growing, and many companies are moving toward automated performance testing. Telia uses HP Performance Center for performance testing and wants to explore the market for new performance testing tools. The study compares two performance testing tools: HP Performance Center and BlazeMeter.The study is based on several criteria, which are cost, usability, functionality, efficiency and agile performance testing. The report contains information about the literature review that led to the creation of the framework and interview questions. The purpose of the report is to inform the reader about which tool has better usability, functionality, efficiency and costs and which tool can be used in agile performance testing. / Behovet för prestandatestning växer och många företag går också mot automatiserad prestandatestning. Telia använder i dagsläge Performance Center för prestandatestning, de vill utforska marknaden för nya prestanda testverktyg. Studien går ut från att utvärdera två perstanda testverktyg som är BlazeMeter och HP Performance Center. Studien mellan BlazeMeter och Performance Center byggs på flera kriterier som är kostnad, användbarhet, funktionalitet, effektivitet och agil prestanda testning. Rapporten innehåller information om litteraturstudien, hur ramverket skapas och intervju frågorna som baseras på ramverket. Syftet med rapporten är att ge läsaren information om vilket verktyg som har bättre användbarhet, funktionalitet, effektivitet och verktyget som kan användas i agil prestanda testning.
282

A Comparative Analysis of User Interfaces in the Calling Functionality of Infotainment Systems among Popular Cars in Romania : Investigating UX and Usability Design Principles for In-car Infotainment Systems.

Kandiyoti Eskenazi, Semi, Cimpan, Bogdana-Floriana January 2023 (has links)
As cars become more integrated into people’s lives, the design of in-car infotainment systems has become increasingly important. This thesis explores the user experience and Usability design principles of the calling functionality within the infotainment systems of five of the most common cars in Romania. The research examines the design principles that underpin these systems, using the European Statement of Principles on Human-Machine Interface (HMI) as a reference. The primary methodology involved two stages of surveys. The first survey gathered demographic information, car ownership details, and participants' experiences with their infotainment systems. This data was then used to identify the most common cars for the second survey, which further investigated user preferences for different infotainment interfaces. Analysis of the survey results reveals significant patterns in user preferences, with ease of use and convenience emerging as crucial factors in user satisfaction. The study highlights the importance of button placement, interface design, and layout in determining user experience. The most preferred interfaces were those which aligned with HMI principles, emphasizing simplicity, clarity of information, and ease of navigation. Despite certain limitations, such as the small sample size and potential for self-reporting bias, the research provides important insights into user preferences and the impact of design principles on user experience. The findings underscore the need for interface designs that are both user-friendly and align with established HMI guidelines. The implications of these findings extend to the broader fields of Human-Computer Interaction and Automotive User Interfaces, emphasizing the importance of user-centered design in enhancing user experience and satisfaction. Future research could expand upon these findings, exploring the impact of aesthetic design factors and the potential for personalized interface options.
283

Mining Metabolic Networks and Biomedical Literature

Cakmak, Ali January 2009 (has links)
No description available.
284

SYNTHESIS OF TETRABENZO[18]CYCLYNE CROSS-CONJUGATED MACROCYCLES WITH FOCUS ON THE DONOR-ACCEPTOR INDUCED FUNCTIONALITY

Ponsot, Amanda Eileen 09 August 2010 (has links)
No description available.
285

En jämförelsestudie av fritidsbåtar mellan The Candela Seven och AMT 230 GP / A comparative study of leisure boats between the Candela Seven and AMT 230 GP

Pulat, Arpat, Zaierding, Tayierjiang January 2021 (has links)
Detta examensarbete går ut på att utföra en analys i form av en jämförelsestudie av två fritidsbåtar med funktions, ekonomisk samt hållbarhetsaspekter i fokus. Projektet utgår samt är inriktad på en eldrivenbärplansbåt The Candela Seven från elmotorbåtsproducent Candela Speed Boat AB där båten jämförs med motorbåten AMT 230 GP från Advanced Marine Tech Premium Boats och utvärderas dels med hjälp av Havsmiljöinstitutets samarbete mellan olika institutioner i Sverige som referensram. Projektmålen är att genom analys och utvärderingar av jämförelsearbete utse båten som ska prioriteras mellan Candela Seven och AMT 230 GP samt komma med eventuella rekommendationer ur funktions-, ekonomiska samt hållbarhetsperspektiv. Arbetet startade med en nulägesanalys för att skapa insikt i produktfunktionalitet av båtarna, vilka ekonomisk och hållbarhetsfördelar produkten har samt hur marknaden ser ut för elbåtar med kundbehov i fokus. För vidareanalys av insamlade data och fakta för jämförelsearbete genomfördes SWOT- och kvantitativa analysmetoder samt genom matematiska resonemang och analyser identifiera båtens egenskaper och fördelar jämfört med konkurrenten. I jämförelseanalys används jämförelsematris för värdering och sammanställning av olika parametrar mot varandra samt utse båten som ska prioriteras. I jämförelseanalysen med olika parametrar visades Candela Seven är en gynnsammare båt att välja eller köpa och som prioriteras i jämförelse med AMT 230 GP. Fokus kan bli att hitta flera kunder som är intressanta, eller produktanpassa för att uppfylla kunders önskemål. Nulägesanalys genomfördes som visar att en huvudkonkurrent med bensindriven båt identifierades samt är ett substitut som utmanar produkten. Utmärkta egenskaper från SWOT och Kvantitativa-analysen är att Candela Seven är energisparande samt lönsammare att driva med mindre underhåll jämfört med AMT 230 GP. Dessutom är produkten miljövänligare i körning med hållbarhetstänkande egenskaper och design. / This thesis is based on performing an analysis in the form of a comparative study of two leisure boats with functional, economic and sustainability aspects in focus. The project is based and focuses on an electric hydrofoil boat The Candela Seven from electric motorboat manufacturer Candela Speed Boat AB where the boat is compared with the motorboat AMT 230 GP from Advanced Marine Tech Premium Boats and evaluatedpartly with the help of the Institute of Marine Environment's cooperation betweendifferent institutions in Sweden as a reference framework. The project goals are to, through analysis and evaluations of comparative work,designate the boat that will be prioritized between Candela Seven and AMT 230 GP andgive eventual recommendations from a functional, financial and sustainabilityperspective. The work started with a current situation analysis to create insight into the productfunctionality of the boats, what economic and sustainability benefits the product hasand what the market looks like for electric boats with customer needs in focus. Forfurther analysis of collected data and facts for comparative work, SWOT andquantitative analysis methods were performed and through mathematical reasoning andanalyzes to identify the boat's properties and advantages compared to the competitor. In comparison analysis, a comparison matrix is used for valuation and compilation ofdifferent parameters against each other and to designate the boat to be prioritized.In the comparison analysis with various parameters, Candela Seven was shown to be amore favorable boat to choose or buy and which is prioritized in comparison with theAMT 230 GP. The focus can be on finding more customers that are interesting, orproduct adaptation to fulfill customer needs. The current situation analysis was carried out which shows that a main competitor witha petrol-powered boat was identified and is a substitute that challenges the product.Excellent features from the SWOT and Quantitative analysis are that Candela Seven isenergy-saving and more profitable to operate with less maintenance cost compared to the AMT 230 GP. In addition, the product is more environmentally proficient whendriving with sustainability-thinking properties and design.
286

Effets des radiations gamma et des électrons de basse énergie sur la fonctionnalité de l'ADN / Effect of gamma radiation and low energy electron on the DNA functionality

Sahbani, Saloua January 2014 (has links)
Résumé : Il est généralement admis que les cassures double-brin (CDB) de l’ADN sont parmi les lésions les plus toxiques induites par les radiations ionisantes (RI). Les CDBs non ou mal réparées peuvent conduire à une instabilité génomique et à la mort cellulaire. La chimioradiothérapie concomitante est l’une des modalités la plus efficace pour le traitement de certains cancers surtout en stade avancé. Le rendement des CDBs a augmenté quand l’ADN a été irradié en présence de cisplatine avec des électrons de basse énergie (EBEs). Notre étude a pour objectif de réévaluer la contribution des CDBs et d’autres lésions induites par les RI dans la létalité cellulaire. L'effet des RI sur la fonctionnalité de l’ADN plasmidique modifié ou non de façon covalente par le cisplatine a été étudié par mesure de l'efficacité de transformation du plasmide dans E. coli. Les complexes cisplatine-ADN ont été préparés de telle sorte qu’il y avait en moyenne deux adduits de cisplatine par plasmide tel que mesuré par ICP-MS. Nos échantillons ont été irradiés en solution avec des doses croissantes de rayonnements gamma (137Cs). La présence de cisplatine a augmenté la formation des CDBs par un facteur de 2.6 par comparaison avec l'ADN non modifié. Malgré cette augmentation, le rendement des CDBs reste très faible et ne peut pas expliquer la perte de fonctionnalité observée. Alors que, les dommages multiples localisés (LMDS) (non-DSB cluster damage) donnant naissance à des CDBs sous l’action des enzymes de réparation la formamidopyrimidine [fapy]-DNA glycosylase (Fpg) et l’endonuclease III (Nth) où leur rendement a été augmenté d’un facteur de 2.1 lorsque l’ADN a été irradié en présence de cisplatine, ont pu expliquer la perte de fonctionnalité observée. Ces résultats suggèrent que le cisplatine peut agir, non seulement comme un agent chimiothérapeutique, mais aussi comme un radiosensibilisateur efficace par addition d’autres lésions à l’ADN. Aussi, pour la première fois nous avons pu évaluer l’effet des EBEs sur la létalité cellulaire. Des films d'ADN ont été préparés en utilisant la méthode d’adsorption douce sur un substrat de graphite pyrolytique, en présence de 1,3- diaminopropane (Dap[indice supérieur]2+) et ont été irradiées avec des EBEs 10 eV. Nous avons pu conclure, qu’en plus des CSBs, CDBs et des dommages de base, les EBEs sont capables aussi d’induire des LMDS (non-DSB cluster damage) et induire la perte de fonctionnalité de l’ADN. Le rendement des CDBs est très faible d’où ils n’ont pas pu expliquer la perte de fonctionnalité de plasmide observée, après irradiation avec les EBEs. Le rendement très faible des LMDS (non-DSB cluster damage) ne peut pas expliquer la perte de fonctionnalité de l’ADN. Il semble que les EBEs sont capables d’induire des dommages très proches les uns des autres et qui ne peuvent pas être révélés par les enzymes de réparation Fpg et Nth. Plus les dommages sont proches les uns des autres, plus leur réparation est difficile, car une de ces lésions peut inhiber la réparation de l’autre la plus proche. // Abstract : It is generally accepted that DNA double-strand breaks (DSB) are among the most toxic lesions induced by ionizing radiation (IR). Unrepaired or misrepaired DSB can lead to genomic instability and cell death. It is known that concomitant chemoradiation therapy is one of the most preferred methods for the treatment of certain cancers especially in advanced stage. The yield of DSBs was increased when DNA was irradiated with low energy electron (LEEs). The aims of our study was to reassess the contribution of DSBs and other lesions induced by indirect and direct effect of IR in cell lethality. The effect of IR on the DNA functionality of the plasmid modified covalently with cisplatin was studied by measuring the transformation efficiency of the plasmid in E. coli. Cisplatin-DNA complexes were prepared such that there was an average of two cisplatin adducts per plasmid as measured by ICP-MS. Aqueous solutions of the samples were irradiated with 137Cs [gamma]-rays at various doses. Gel electrophoresis analysis shows that cisplatin enhances, by a factor of 2.6, the formation of DSB by [gamma]-rays relative to those in unmodified DNA. Despite this increase, the yield of DSBs is very low and cannot explain the loss of functionality observed after transformation with plasmids modified with cisplatin. While locally multiple damaged sites (LMDS) revealed by repair enzymes Fpg (Formamidopyrimidine [fapy]-DNA glycosylase) and Nth (Endonuclease III) as DSB (nonDSB cluster damage), where their yield was increased by a factor of 2.1 when DNA was irradiated in the presence of cisplatin were able to explain the observed loss of DNA functionality. These results suggest that cisplatin may act not only as a chemotherapeutic agent, but also as an effective radiosensitizer by addition of other DNA lesions. For the first time, we could also evaluate the effect of low energy electrons (LEEs) on DNA functionality. Highly ordered DNA films were prepared on pyrolytic graphite by molecular self-assembly using 1,3-diaminopropane ions (Dap[superscript]2+) to bind together the plasmids and irradiated with LEE (10 eV). We concluded that in addition to CSBs, DSBs and base damage, LEEs induced the formation of non-DSB cluster damage and also induced the loss of DNA functionality under LEE irradiation. The yields of DSBs and of non-DSB cluster damage are too low and so one unable to explain the loss of DNA functionality. It seems that LEEs are able to induce a high complex damage that cannot be revealed by repair enzymes Fpg and Nth. The high complex damage is difficult to repair possibly because the repair of one lesion, may inhibit the repair of another.
287

La notion de fonctionnalité en droit canadien : quels fondements pour quels usages?

Jonnaert, Caroline 01 1900 (has links)
Ce mémoire analyse la notion de fonctionnalité. D'origine jurisprudentielle, ce concept tend à maintenir la dichotomie traditionnelle entre le régime des marques de commerce et celui des brevets. À la lecture des jugements rendus en la matière, le maintien d'une telle dichotomie empêcherait notamment de prolonger indûment un monopole échu sous le régime des brevets par l'enregistrement d'une marque de commerce. Cette étude tente de mieux cerner le concept de fonctionnalité et, plus précisément, de justifier son existence. Pour ce faire, une étude approfondie des régimes des marques de commerce et des brevets, nous permet de comprendre que chacun de ces corps de règles répond à une logique différente. Les fonctions des marques de commerce et des brevets sont en effet distinctes et aucun chevauchement ne semble être permis. Cette situation est d'ailleurs propre à ces régimes spécifiques. Un examen de l'étendue de la notion de fonctionnalité nous permet de constater que d'autres droits de propriété intellectuelle peuvent coexister. À titre d'exemple, nous croyons qu'une intersection est possible entre les régimes des dessins industriels et des marques de commerce. À l'issue de ces recherches, nous constatons que la notion de fonctionnalité est un principe jurisprudentiel bien établi en droit canadien visant à empêcher tout renouvellement à perpétuité d'un brevet par le biais du droit des marques de commerce. L'existence de ce principe nous semble être justifiée en matière de marques de commerce et de brevets. Cette conclusion pourrait toutefois différer dans le cadre d'autres droits de propriété intellectuelle, les fonctions de ces autres régimes semblant permettre des chevauchements. / This memory analyzes the notion of functionality. Of case law origin, this concept tends to maintain the traditional dichotomy between trademarks and patents regimes. In light of judgments rendered on that matter, the preservation of such dichotomy would notably prevent from illegally prolonging a monopoly fallen under the regime of patents by the registration of a trademark. This study tries to understand the concept of functionality and, more specifically, to justify its existence. In order to reach this goal, a detailed study of the regimes of trademarks and patents lead us to conclude that each of these bodies of rules answers to a different logic. Indeed, the functions of trademarks and patents are different and no overlapping seems to be allowed. This situation is particular to these two specific regimes. An examination of the area of the notion of functionality leads us to notice that other rights of intellectual property can coexist. For example, we believe that an intersection is possible between the regimes of industrial designs and trademarks. As a conclusion, we notice that the notion of functionality is a well established principle in Canada which tends to prevent any perpetual renewal of a patent under the trademarks regime. We believe that the existence of this concept is justified under trademarks and patents laws. However, this conclusion could differ within the framework of the other intellectual property rights, since these other rights' functions seem to allow an intersection between them.
288

Towards the functionality South African internet banking websites should provide to address the needs of generation-Y users

Mtimkulu, Sebabatso 07 1900 (has links)
Despite the widespread adoption of Internet banking, no guidelines exist on what functionality the techno-savvy Generation-Y customer segment (20–37 years) expects from Internet banking websites. This research investigated the functionality that South African Generation-Y customers require from this transacting platform. A user-centred design philosophy with a mixed method research design was used. The technological characteristics of Generation-Y, abstracted from the literature, were aligned with functionality trends of future Internet banking websites to formulate an initial list of Internet banking functionality guidelines. These were evaluated using a survey and interviews, and were also used in a heuristic evaluation of the Internet banking platforms of five South African banks. The findings were integrated to synthesise functionality guidelines. A visual representation of these guidelines was constructed as wireframes for evaluation by Generation-Y users. This study makes a contribution by providing a validated list of Internet banking functionality guidelines for Generation-Y banking customers. / College of Engineering, Science and Technology / M. Tech. (Information Technology)
289

Desenvolvimento de um escore de funcionalidade da lipoproteína de alta densidade (HDL) e sua associação com algoritmos de predição de risco cardiovascular e aterosclerose subclínica em indivíduos brasileiros / Development of a high density-lipoprotein (HDL) functionality score associated with predictive cardiovascular risk algorithms and subclinical atherosclerosis in Brazilian individuals

Freitas, Maria Camila Pruper de 16 May 2019 (has links)
Introdução: estudos recentes demonstram que o aumento do colesterol na lipoproteína de alta densidade (HDL-C), induzido por medicamentos ou mutações genéticas, não é associado à redução de eventos coronarianos. A lipoproteína de alta densidade (HDL) apresenta aspectos funcionais distintos em relação ao seu papel cardioprotetor. Objetivo: desenvolver um escore de funcionalidade da HDL (EFH) e avaliar a sua associação com algoritmos de predição de risco cardiovascular e aterosclerose subclínica em indivíduos brasileiros. Metodologia: trata-se de um estudo transversal composto por duas etapas. Na 1ª etapa, o EFH preditor de risco cardiovascular (EFH-RCV) foi desenvolvimento e validado a partir de uma subamostra do estudo CARDIONUTRI (n=354). Na 2ª etapa, o EFH preditor de aterosclerose subclínica (EFH-AS) foi desenvolvido e validado com dados de uma subamostra do estudo ELSA-Brasil (n=4549). No estudo CARDIONUTRI foram avaliadas a atividade da paraoxonase 1 (PON1) e da proteína de transferência de ésteres de colesterol (CETP), a concentração da apolipoproteína AI (APOAI), a capacidade antioxidante da HDL (lag time) e as subfrações da HDL pelo método Lipoprint®. O estudo ELSA-Brasil avaliou as subfrações da HDL pelo método Vertical Auto Profile (VAP) e Ressonância Magnética Nuclear (RMN), e a aterosclerose subclínica por tomografia computadorizada, quantificação da calcificação da artéria coronária (CAC) e calculo do escore da CAC. Resultados: no desenvolvimento do EFH-RCV, a HDL grande apresentou maior força de associação com o risco cardiovascular no modelo múltiplo final (OR = 0,797; p <0,001). O EFH-RCV demonstrou bom desempenho em relação ao escore de risco de Framingham (AUC = 0,899; p <0,001), escore de risco de Reynolds (AUC = 0,722; p <0,001) e Adult Treatment Panel III/2013 (AUC = 0,864; p <0,001). Além disso, apresentou boa reprodutibilidade e correlação com aterosclerose subclínica, quando testado na amostra do estudo ELSA-Brasil, utilizando medidas da HDL grande derivadas do método VAP (AUC = 0,864; p <0,001 e r = 0,252 p <0,001) ou do método de RMN (AUC = 0,876; p <0,001 e r = 0,277; p <0,001). O EFH-AS foi desenvolvido a partir do tamanho da HDL (nm), que apresentou a associação mais forte com aterosclerose subclínica no modelo múltiplo final (OR = 0,549; p <0,001) e demonstrou bom desempenho (AUC = 0,769; p <0,001). Conclusão: o EFH apresentou associações mais fortes com o risco cardiovascular e a aterosclerose subclínica, independente do HDL-C, com destaque para a HDL grande. Os resultados controversos entre as subfrações da HDL e o risco cardiovascular parecem manter relação com as metodologias distintas utilizadas nas análises. Portanto, a validação dos métodos e a inclusão do tamanho da HDL como marcador de risco cardiovascular revela um futuro promissor como adjuvante na estimativa do risco cardiovascular, manejo de medicamentos e tomada de decisões na prática clínica. / Introduction: current studies have not presented association between high density-lipoprotein cholesterol (HDL-C) increase, induced by drugs or genetic mutations, and coronary events reduction. HDL plays different functional cardioprotective role. Objective: to develop a HDL functionality score (HFS) and to assessment its association with predictive cardiovascular risk algorithms and subclinical atherosclerosis outcomes in Brazilian subjects. Methods: cross-sectional study based in two steps. In the first step, the HFS predictor of cardiovascular risk disease (HFS-CVR) was developed and validated on CARDIONUTRI study subsample (n=354). In second step the HFS predictor of subclinical atherosclerosis (HFS-SA) was developed and validated on ELSA-Brasil study subsample (n=4549). CARDIONUTRI study evaluated paraoxonase 1(PON1) and cholesterol ester transfer protein (CETP) activity, apolipoprotein AI (APOAI) concentration, HDL antioxidant capacity, and HDL subfractions by standard Lipoprint® method. ELSA-Brasil study evaluated the size of HDL and subfractions by Vertical Auto Profile (VAP) and Nuclear Magnetic Resonance (NMR) method, and the diagnosis of subclinical atherosclerosis by computed tomography, quantifying coronary artery calcification (CAC) and CAC score. Results: in the development of HFS-CVR, the large HDL presented greater strength of association with cardiovascular risk in the multiple final model (OR = 0.797; p <0.001). The HFS-CVR showed satisfactory performance by Framingham risk score (AUC = 0.899; p <0.001), Reynolds risk score (AUC = 0.722; p <0.001) and Adult Treatment Panel III/2013 guidelines (AUC = 0.864; p <0.001). In addition, HFS-CVR presented satisfactory reproducibility and was associated with subclinical atherosclerosis on ELSA-Brasil sample using large HDL measurements derived from the VAP method (AUC = 0.864; p <0.001 and r = 0,252; p <0,001) or the NMR method (AUC = 0.876; p <0.001 and r = 0.277; p <0,001). HFS-AS was developed from the HDL size (nm), because presented greater association with subclinical atherosclerosis in the final multiple model (OR = 0.549; p <0.001). HFS-AS demonstrated satisfactory performance (AUC = 0.769; p <0.001). Conclusion: the HFS demonstrates strong association with cardiovascular risk and subclinical atherosclerosis, independent of HDL-C, with emphasis on large HDL. Controversial results, between HDL subfractions and cardiovascular irsk seem to maintain a relation with the different methodologies used in analysis. Therefore, the validation of the methods and the inclusion of the HDL size as a cardiovascular risk marker reveal a promising future as an adjunct in the estimation of cardiovascular risk, drug management and decision making in clinical practice.
290

Human natural regulatory T cells subsets

Lei, Hong 15 May 2014 (has links)
Regulatorische T-Zellen (Treg) eröffnen neue immuntherapeutische Wege zur Kontrolle unerwünschter Immunreaktionen, jedoch wirft die Heterogenität dieser Zellen die Frage auf, welche Treg-Population für die klinische Anwendung. Darauf basierend werden in dieser Arbeit drei Fragestellungen bearbeitet: i) Bestimmung der Häufigkeit von Tregs und deren Subpopulationen in verschiedenen Altersgruppen bei Empfängern einer Organtransplantation (Tx) und einer gesunden Kontrollgruppe; ii) Vergleich der Suppressorkapazität verschiedener Treg-Populationen und in vitro-Expansion der Zellen unter Erhaltung ihrer Funktionalität; iii) Klärung der Differenzierungsmerkmale von Tregs und deren Verknüpfung mit konventionellen T-Zellen (Tconv) mittels Analyse des T-Zell-Rezeptor- (TCR) Repertoires. Sowohl bei gesunden Probanden als auch bei Tx-Empfänger konnte eine altersabhängige Verschiebung von naiven (TregN) hin zu dominant zentralen Gedächtnis-Zellen (TregCM) beobachtet werden, Treg von Tx-Empfängern hatten mehr Effektor-Memory-Zellen (EM) und sie waren mehr aktiviert. In Bezug auf die Kontrolle der frühen Tconv zeigen TregCM eine erhöhte Suppressorkapazität im Vergleich zu TregN. Außerdem sind im Gegensatz zu TregN nur TregCM dazu in der Lage, Apoptose bei Responderzellen zu induzieren. Der Grund hierfür könnte in der stärkeren Expression von CTLA-4 auf TregM liegen. Die Expansionskultur führte zur phänotypischen Veränderung der TregN, deren Umwandlung in TregCM mit einer verbesserten Suppressoraktivität verbunden ist. Die Daten legen nahe, dass das Expandieren mit gesamt Treg für die Adoptive-Treg-Therapie optimal sind, da sie der größte Anteil von ihnen die hochpotenten TregCM sind. TCR-Studien mittels Next Generation Sequencing zeigen weiter, dass TregM aus TregN entstehen, anstatt aus Tconv, in einem Antigen-gesteuerten Prozess. Diese Daten belegen erstmalig neue Erkenntnisse hinsichtlich der Unterschiede der TCR-Repertoires von TregM und Tconv beim Menschen. / Regulatory T cells (Treg) offer new immunotherapeutic options to control undesired immune reactions, but the heterogeinetiy of Treg raises the question which Treg population should be used for clinical translation Thus, this project involves three main parts: i) investigating Treg frequency and subsets distribution with age in healthy donors and transplant (Tx) patients; ii) comparing the suppressive capacity of Treg subsets and expanding them in vitro without losing functionality; iii) clarifyjing the differiation relationship of Treg subsets and their relation to conventional T cells (Tconv) by T cell receptor (TCR) repertoire analysis. From both healthy donors and Tx patients, an age-dependent shift from naïve Treg (TregN) to the dominant central-memory Treg (TregCM) was observed,; However,Treg in Tx patients contained more effector-memory EM cells, , and they were pre-activated due to the exposure to allo antigens,. Regarding control of early Tconv activation, TregCM showed enhanced suppressive capacity compared to TregN; furthermore, only TregCM could induce apoptosis of responder cells while TregN could not, which may result from thehigherexpression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) on TregM. Following in vitro expansion of the Treg subsets, however, TregN converted mainly into TregCM phenotype with enhanced suppression activity. The poor proliferation capacity of TregEM might indicate EM as the terminal differential stage. These data suggest that expansion with total Treg is optimal for adoptive Treg therapy as the majority of them are the highly potent TregCM. Lastly, TCR repertoire study by next generation sequencing (NGS) indicate that TregM derived from TregN rather than Tconv in an antigen-driven process. The highest similarity of the TCR repertoires was observed between TregCM and TregEM. These data reveal new insights for the first time into the distinct TCR repertoires of Treg subsets and Tconv in human by NGS technology.

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