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.

Durch Parasiten stellen eine starke Gefährdung für die Aquakultur dar. Die durch diplomonaden Flagellaten bei der Regenbogenforelle Oncorhynchus mykiss verursachte Morbidität und Mortalität wurde bisher in Deutschland noch nicht gründlich untersucht. Ich habe diese Parasiten mittels SEM & TEM charakterisiert und wurde die Art Spironucleus salmonis bestimmt. Erstmals konnten die caudale Projektion, sich entleerende Vakuolen und verformbare Kernloben nachgewiesen werden. Ich untersuchte Mikrohabitatpräferenz von des Parasiten sowie pH-Profile in vier Darmabschnitten der Fische. Das Vorkommen und die Dichte von S. salmonis war in der Pylorusregion wesentlich höher als in anderen Bereichen. Das pH-Profil war bei infizierten und nicht infizierten Fischen gleich. Der optimale pH-Wert für S. salmonis war 7,1-7,5. Ich habe die Lebenszyklus der Diplomonaden mittels LM & SEM unter Kulturbedingungen untersucht. Die Enzystierung begann mit der Anheftung von Trophozoiten mit der Spitze der adhäsiven hinteren Flagellen aneinander oder an Fremdkörper. Die pyriformen Trophozoiten wurden kugelförmig, und die vorderen Flagellen inaktiv. Oberflächenbläschen produzierten eine lichtbrechende Zystenwand. Dies ist der erste Beschreibung der Multifunktionalität von Flagellen bei Diplomonaden. Ich untersuchte pathogene Mechanismen und sezierte die Pylorusregion sowie die Leber mittels H&E, PAS/AB. Bei infizierten Fischen trat eine signifikante Hypertrophie der Becherzellen auf. Zu erkennen war eine Hyperaktivität der Becherzellen, jedoch keine Hyperplasie. Ich entwickelte einen in vitro  Plasma-Inkubationstest zur Bestimmung der Suszeptibilität von Regenbogenforelle, Karpfen und Störe. Die unterschiedliche Resistenz von Stör, Karpfen und Regenbogenforelle gegen S. salmonis entsprechend zu den epizootiologischen Daten. Meine Untersuchungen führten zu einem neuen diagnostischen Hilfsmittel, Vorschlägen für neue Behandlungsmethoden, zu verbesserten in vitro-Kulturbedingungen und einem Modellsystem für die Multifunktionalität von Flagellen und flagellaren Signaltransduktion. / Parasitic diseases pose a significant threat to aquaculture. Diplomonad flagellates in rainbow trout Oncorhynchus mykiss are associated with morbidity and mortality; but in Germany has not been thoroughly studied. I characterised the species by SEM & TEM, which revealed Spironucleus salmonis, allowed its complete description including newly showing the caudal projection, discharging vacuoles, and deformable nuclear lobes; diagnostic keys were improved. The microhabitat preference of diplomonads was tested by recording occurrence and density of infection, and pH profile in 4 intestinal regions in fish. Occurrence and density of S. salmonis were significant higher in the pyloric region than elsewhere. The pH profile in uninfected and infected fish was similar; a causal relationship between microhabitat preference and pH was unlikely, and the optimal pH was between 7.1 – 7.5. I described life cycle and encystment using light and SEM. Encystment in culture began by trophozoites attaching at tip of adhesive posterior flagella to each other/debris. Pyriform trophozoites became sub-spherical, anterior flagella inactive, surface blebs produced a refractile cyst wall. Cysts clusters may exceed minimum infective dose for new infection; suggesting new treatment target. This is the first report of multi-functionality of flagella in diplomonads. I investigated pathogenic mechanism of diplomonads by sectioning and staining the pyloric region of the intestine and liver with H&E, and PAS/AB. There was significant hypertrophy of goblet cells in infected fish. The hyperactivity of goblet cells was seen, but no hyperplasia. This hyper-production of mucus may decrease nutrient absorption, underlying impaired growth in S. salmonis infected fish. I developed an in vitro plasma incubation test to predict host susceptibility of rainbow trout, carp, and sturgeon. The test showed the hierarchy of resistance of S. salmonis in sturgeon > carp > rainbow trout; this parallels epizootiological data. My research yielded new diagnostic tool, suggested new treatment target, improved in vitro conditions, and new model system for multi-functionality of flagella and flagellar signalling.

With the advent of autonomous systems and deep learning systems, safety pertaining to these systems has become a major concern. The existing failure analysis techniques are not enough to thoroughly analyze the safety in these systems. Moreover, because these systems are created to operate in various conditions, they are susceptible to unknown safety issues. Hence, we need mechanisms which can take into account the complexity of operational design domains, identify safety issues other than failures, and expose unknown safety issues. Moreover, existing safety analysis approaches require a lot of effort and time for analysis and do not consider machine learning (ML) safety. To address these limitations, in this dissertation, we discuss an artificial-intelligence driven model-based methodology that aids in identifying unknown safety issues and analyzing ML safety. Our methodology consists of 4 major tasks: 1) automated model generation, 2) automated analysis of component state transition model specification, 3) undesired states analysis, and 4) causal factor analysis. In our methodology we identify unknown safety issues by finding undesired combinations of components' states and environmental entities' states as well as causes resulting in these undesired combinations. In our methodology, we refer to the behaviors that occur because of undesired combinations as off-nominal behaviors (ONBs). To identify undesired combinations and ONBs that aid in exposing unknown safety issues with less effort and time we proposed various approaches for each of the task and performed corresponding empirical studies. We also discussed machine learning safety analysis from the perspective of machine learning engineers as well as system and software safety engineers. The results of studies conducted as part of our research shows that our proposed methodology helps in identifying unknown safety issues effectively. Our results also show that combinatorial methods are effective in reducing effort and time for analysis of off-nominal behaviors without overlooking any dependencies among components and environmental entities of a system. We also found that safety analysis of machine learning components is different from analysis of conventional software components and detail the aspects we need to consider for ML safety.

本論文欲研究虛擬角色於既有智慧財產權法制下的保護途徑，並以商標法與著作權法為核心，探討與虛擬角色保護相關之智慧財產權議題；以及著作權與商標法併用於保護虛擬角色的趨勢之下，對公共領域可能造成的影響，並由此進一步討論利用人地位之保護。 漫畫、卡通等文化創意產業的繁榮，進一步帶動了消費者對於角色相關商品的喜愛與需求，近來隨著網路、智慧型手機的發展，不僅提升了角色人物的普及率，也使得角色的呈現方式更加多元，角色經濟所帶來經濟效益與日俱增，且儼然成為文創產業未來的產品競爭力來源。然而，諸如角色造型與其背景故事，這些藝術創作的心血結晶應如何透過既有智慧財產權法律體系加以保護? 又創作人在尋求智慧財產權保護的過程中會遭遇何等障礙?目前我國學界尚未有深入之研究探討，故為本論文所欲研究之重點。 本論文將以虛擬角色著作權保障之議題為始，從比較法角度探討虛擬角色著作權保護之不同判斷標準，以及各判斷標準下所衍生之問題；再探討虛擬角色取得商標權保護之可能性，以及權利人在取得商標保護過程中所可能面臨之阻礙，並進一步論述虛擬角色商標權保護範圍之問題。 此外，在探討如何以智慧財產權法保護角色之餘，如何平衡保護利用人的權益，更是智慧財產權法一個恆久而困難的問題。由於虛擬角色對其他創作人而言，亦是一個具有發展性的創作素材；如果過度保護虛擬角色，則可能對其他利用人的創作構成阻礙，造成創作火花熄滅的負面效應 。因此，本論文亦將虛擬角色保護的主題與思想表達合併原則的運用、保護商標戲謔仿作等議題相互結合，探討擴大角色智慧財產權保護的趨勢下，如何對利用人地位給予應有的保護。 最後，則冀望透過本論文所提出的歸納結果與淺見，能夠提供相關文創產業工作者參考，進而使國內文創產業重視虛擬角色相關智慧財產權的策略佈局，從而引領我國文化創意產業拓展商機。

Preliminary investigation at the beginning of this research showed that informatics on point-of-care (POC) devices was limited to basic data generation and processing. This thesis is based on publications of several studies during the course of the research. The aim of the research is to model and analyse information generation and exchange in telehealth systems and to identify and analyse the capabilities of these systems in managing chronic diseases which utilise point-of-care devices. The objectives to meet the aim are as follows: (i) to review the state-of-the-art in informatics and decision support on point-of-care devices. (ii) to assess the current level of servitization of POC devices used within the home environment. (iii) to identify current models of information generation and exchange for POC devices using a telehealth perspective. (iv) to identify the capabilities of telehealth systems. (v) to evaluate key components of telehealth systems (i.e. POC devices and intermediate devices). (vi) to analyse the capabilities of telehealth systems as enablers to a healthcare policy. The literature review showed that data transfer from devices is an important part of generating information. The implication of this is that future designs of devices should have efficient ways of transferring data to minimise the errors that may be introduced through manual data entry/transfer. The full impact of a servitized model for point-of-care devices is possible within a telehealth system, since capabilities of interpreting data for the patient will be offered as a service (c.f. NHS Direct). This research helped to deduce components of telehealth systems which are important in supporting informatics and decision making for actors of the system. These included actors and devices. Telehealth systems also help facilitate the exchange of data to help decision making to be faster for all actors concerned. This research has shown that a large number of capability categories existed for the patients and health professionals. There were no capabilities related to the caregiver that had a direct impact on the patient and health professional. This was not surprising since the numbers of caregivers in current telehealth systems was low. Two types of intermediate devices were identified in telehealth systems: generic and proprietary. Patients and caregivers used both types, while health professionals only used generic devices. However, there was a higher incidence of proprietary devices used by patients. Proprietary devices possess features to support patients better thus promoting their independence in managing their chronic condition. This research developed a six-step methodology for working from government objectives to appropriate telehealth capability categories. This helped to determine objectives for which a telehealth system is suitable.

Mémoire en jeu vidéo / Un survol des théories sur le point de vue et sur l’ocularisation au cinéma permet de constater que les recherches ont été bien menées dans ce champ d’étude. Or, le même bilan ne peut pas être fait en jeu vidéo. Le point de vue vidéoludique n’a pas été analysé et théorisé avec la même exhaustivité et le même approfondissement. Beaucoup de lacunes sont encore visibles et le but de ce mémoire est justement d’en cibler quelques-unes et de les combler. Cette recherche se penche ainsi sur les points de vue en jeu vidéo et plus précisément, sur ceux que l’on retrouve à l’intérieur des phases interactives (les cinématiques sont par exemple exclues) dans les oeuvres tridimensionnelles. Une typologie de l’ocularisation vidéoludique, c’est-à-dire une nouvelle catégorisation des différents types de visualisation, est présentée, décortiquée et exemplifiée tout au long de ce mémoire. Celle-ci est plus approfondie que celles déjà développées par le passé, car elle prend en compte une plus grande variété de caractéristiques : l’ancrage, le positionnement, la mobilité et le contrôle offert au joueur. Aussi, elle détaille l’impact des différents points de vue sur l’expérience de l’utilisateur en privilégiant deux axes : l’esthétique et la fonctionnalité. À terme, ce mémoire permet d’instaurer une théorie de l’ocularisation plus aboutie dans les études vidéoludiques. / An overview of the theories on the point of view and on the ocularization in cinema shows that the researches were well conducted in this field of study. However, the same report cannot be done in video game. The notion of point of view has not been analyzed and theorized with the same exhaustiveness and deepening. Many gaps are still visible and the purpose of this thesis is to target some of them and to fill them. This research thus examines the points of view in video games and more specifically, those that are found within the interactive phases (cutscenes are for example excluded) in three-dimensional games. A typology of ocularization, that is to say a new categorization of the different types of visualization, is presented, analyzed and exemplified throughout this thesis. This one goes into deeper details than those already developed in the past, because it takes into account a greater variety of characteristics: anchor, positioning, mobility and control available to the player. Also, it details the impact of the various points of view on the user’s experience by focusing on two axes: aesthetic and functionality. Ultimately, this thesis allows establishing a more elaborate theory on ocularization in video game studies.

Cette recherche s’intéresse au soutien à domicile des personnes âgées dites « en perte d’autonomie » dans un contexte où, d’une part, les inégalités socioéconomiques parmi ce groupe sont marquées et, d’autre part, les services à domicile tendent vers une standardisation et une marchandisation. L’autonomie a été mobilisée comme concept pour mieux appréhender les conditions de vie et les rapports sociaux qui nuisent ou contribuent au bien-être des aînés à domicile, de leur propre point de vue et de celui des auxiliaires familiaux et sociaux qui interviennent auprès d’eux. Ce groupe d’acteurs est généralement évoqué dans la littérature comme ayant une vision sociale et globale des personnes qu’ils visitent, de par leur proximité et intrusion dans l’espace de vie de ces dernières. Le discours dominant par rapport au bien-être des personnes âgées (bien-vieillir ou, en anglais, successful aging) dans la littérature en gérontologie ou dans les documents institutionnels s’articule autour d’une conception fonctionnelle de l’autonomie, au détriment des dimensions plus sociales et relationnelles. Cette recherche a ainsi cherché à investir une perspective sociorelationnelle de l’autonomie, qui se retrouve en sciences sociales chez des auteurs tels que Druhle, Sen, McAll, Honneth, Guillemard et Castoriadis. Ce cadre conceptuel au cœur duquel se trouvent notamment les notions de reconnaissance et de rapports sociaux inégalitaires a servi de porte d’entrée pour analyser 10 entrevues semi-dirigées avec des auxiliaires familiaux et sociaux (qui ont évoqué, chacun, la situation des trois dernières personnes visitées, pour un total de 30 exemples de cas) et 14 entrevues semi-dirigées avec des personnes âgées recevant des services à domicile. Au croisement de ces regards, les résultats de cette recherche suggèrent que les conditions de vie matérielles et relationnelles ont un impact déterminant sur la possibilité pour les aînés de « se sentir vivants » et que pour les personnes les plus défavorisées et/ou isolées, le soutien à domicile se traduit le plus souvent en une situation de « confinement », de « maintien » à domicile. Par rapport à la relation avec les auxiliaires, il apparaît que l’amélioration du bien-être des aînés recevant de l’aide à domicile passe, entre autres, par la création d’un espace relationnel autonome dans lequel la personne existe non seulement comme « corps », mais également comme « esprit ». Par-delà des services offerts, c’est ce type d’interaction (attentif et respectueux des habitudes, intentions et projets qui ont rempli la vie des personnes aidées) qui retient le plus leur attention et mobilise l’essentiel de leur discours sur le soutien à domicile. Il semble également que ce soit parfois en se faisant marginal dans la vie des gens et en créant simplement des espaces favorables à une autonomie collective que le réseau de services peut avoir les impacts les plus positifs sur les personnes, de leur propre point de vue. / This study aims to explore the elder’s home support, more narrowly the experience of people characterized as « in loss of autonomy » in a context where, on one hand, socioeconomic inequalities in this group are important, and, on the other hand, home support services tend toward a standardization and a commoditization. The concept of autonomy has been used to better apprehend the living conditions and the social relations that positively or negatively affect the wellbeing of elders at home, from their own perspective or from those of the visiting caregivers who work with them. The latter are generally mentioned in the literature has having a social and global perspective on the people they visit, as they are closely tied to them and intrude in their own living space. In the gerontology literature and in institutional documents, the dominant discourse related to wellbeing of the elderly (« successful aging » or, in French, « bien-vieillir ») is articulated around a functional conception of autonomy, depriving it of its more social and relational dimensions. This research has developed a social perspective on autonomy grounded in social sciences and based on authors such as Druhle, Sen, McAll, Honneth, Guillemard and Castoriadis. This conceptual framework relies on notions of recognition and social inequality and was used in analyzing our 10 semistructured interviews with caregivers and 14 more with elders receiving homecare. Each of the 10 caregivers were asked to relate their last three visits, adding up to a total of 30 case studies. At the crossroads of these narratives, the results of this research suggest that material and relational living conditions do have a decisive impact on elders’ possibility to « feel alive ». For those most disadvantaged and/or isolated, home support most often translates in situations of containment, of retention at home. With regards to relationships with caregivers, it appears that improvement of elders’ wellbeing receiving home support is related, among other things, to the creation of autonomous relational space where the person exists not only as a « body » with needs, but also as a « spirit ». Beyond the provided services, it is the kind of interaction (careful, mindful, respectful of habits, intentions and projects that fulfill the life of the assisted individuals), that occupies most of their narrative on home care services. According to the elders, from time to time, it seems that the health care system can have more significant positive impact by creating spaces propitious to collective autonomy and with marginal intervention.

My project investigates the intersection of typography and furniture. It questions the language of these objects and compares the two, based on an assumption of similarity. Each supports the assertion of the language system of the other.

Computer security is a growing field in the IT industry. One of the important aspects of the computer security is authentication. Using passwords (something you know) is one of the most common ways of authentications. But passwords have proven to provide weak level of security as they can be easily compromised. Some other ways of authenticating a user are using physical tokens, (something you possess) and biometrics, (something you are). Using any one of these techniques to secure a system always has its own set of threats. One way to make sure a system is secure is to use multiple factors to authenticate. One of the ways to use multiple factors is to use all the three factors of authentication, something you possess, something you are and something you know. This thesis discusses about different ways of authentication and implements a system using three factor authentication. It takes many security aspects of the system into consideration while implementing it, to make it secure.

L'acquisition autonome de representations et de fonctionnalites en robotique pose de nombreux problemes theoriques. Aujourd'hui, les systemes robotiques autonomes sont concus autour d'un ensemble de fonctionnalites. Leurs representations du monde sont issues de l'analyse d'un probleme et d'une modelisation prealablement donnees par les concepteurs. Cette approche limite les capacites d'apprentissage. Nous proposons dans cette these un systeme ouvert de representations et de fonctionnalites. Ce systeme apprend en experimentant son environnement et est guide par l'augmentation d'une fonction de valeur. L'objectif du systeme consiste a agir sur son environnement pour reactiver les representations dont il avait appris une connotation positive. Une analyse de la capacite a generaliser la production d'actions appropriees pour ces reactivations conduit a definir un ensemble de proprietes necessaires pour un tel systeme. Le systeme de representation est constitue d'un reseau d'unites de traitement semblables et utilise un codage par position. Le sens de l'etat d'une unite depend de sa position dans le reseau. Ce systeme de representation possede des similitudes avec le principe de numeration par position. Une representation correspond a l'activation d'un ensemble d'unites. Ce systeme a ete implemente dans une suite logicielle appelee NeuSter qui permet de simuler des reseaux de plusieurs millions d'unites et milliard de connexions sur des grappes heterogenes de machines POSIX. Les premiers resultats permettent de valider les contraintes deduites de l'analyse. Un tel systeme permet d'apprendre dans un meme reseau, de facon hierarchique et non supervisee, des detecteurs de bords et de traits, de coins, de terminaisons de traits, de visages, de directions de mouvement, de rotations, d'expansions, et de phonemes. NeuSter apprend en ligne en utilisant uniquement les donnees de ses capteurs. Il a ete teste sur des robots mobiles pour l'apprentissage et le suivi d'objets.