La sclérose latérale amyotrophique (SLA) est une maladie neurodégénérative due à une dégénérescence des motoneurones. Plus de 40 mutations du gène TARDBP ont été identifiées chez des patients SLA. Les défauts biochimiques de ces mutations étant encore inconnus, les modèles animaux sont présentement la seule mesure possible d’un phénotype. Pour étudier les conséquences physiopathologiques d’une de ces mutations, nous avons développé deux lignées transgéniques de poisson zébré, exprimant le gène humain TARDBP soit de type sauvage, soit avec la mutation G348C liée à la SLA, sous le contrôle d’un promoteur de choc thermique. Ces lignées ont été étudiées sur trois générations, après avoir établi un protocole de choc thermique induisant une expression ubiquitaire du transgène. Les embryons transgéniques de la génération F2 de la lignée exprimant la mutation développent un phénotype moteur suite à un choc thermique de 38.5°C pendant 30 minutes lorsque les embryons sont à 18 heures post-fertilisation. 60% des embryons ont une réponse anormale au toucher. De plus, une réduction de 28% de la longueur de pré-branchement des axones des motoneurones est observée. Ces résultats indiquent que notre lignée exprimant la protéine mutante TDP-43 est un modèle génétique de la SLA prometteur, qui ouvre des perspectives pour la compréhension de la physiopathologie de la maladie et la découverte de molécules thérapeutiques. / Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease due to motoneurons degeneration. More than 40 mutations of the gene TARDBP, coding for the protein TDP-43 have been found in ALS patients. As the biochemical defects of these mutations are not known, in vivo models are currently the only windows onto the pathology. To study the pathophysiological consequences of one of these mutations, we have generated two stable zebrafish transgenic lines, expressing the human gene TARDBP, either the wild-type version, or the G348C mutated version linked to ALS, under the control of a heat shock promotor. These lines were studied for three generation, after establishing a heat shock protocol sufficient to induce a ubiquitous expression of the transgene. The transgenic embryos of the F2 generation of the line expressing the mutant protein develop a motor phenotype after a 38.5°C heat shock for 30 minutes when the embryos are 18 hours post-fertilization. 60% of these embryos have an abnormal touch escaped evoked response, and a 28% reduction of the pre-branching axonal length of the motoneurons axons. These results indicate that our line expressing the mutant TDP-43 protein is a promising genetic model of ALS, opening perspectives for the pathophysiological understanding of the disease, and the discovery of new therapeutics.

A alta competitividade e os avanços tecnológicos propiciaram o surgimento de um novo modelo de terceirização de Tecnologia de Informação (TI), os Provedores de Serviços de Aplicativos (ASP - Application Service Providers). A proposta do modelo ASP é a comercialização de aplicativos de software como serviço. A satisfação dos clientes está diretamente relacionada à qualidade do serviço prestado. Para garantir que sejam fornecidos serviços com qualidade, é fundamental a adoção dos Acordos dos Níveis de Serviços (SLA - Service Levei Agreements) como mecanismo de controle. No entanto, são escassas as informações formalizadas que venham a contribuir com a especificação desses acordos. Propondo-se a contribuir com a compreensão de SLA para ASP, apresenta-se uma pesquisa exploratória do conceito de SLA para ASP, de modelos de qualidade e dos fatores de qualidade a serem considerados nos SLA para garantir a qualidade dos serviços prestados. / lhe current competitiveness of the global market and the continuous technological evolution pushed the risen of a new model of Information Technogy Outsourcing, the Application Service Providers (ASP). The ASP modelproposes the remote delivery of software as a service. Therefore, customers\' satisfaction is strictelly related to the quality of ser\\>ice delivered. It is highly recommended the adoption of Service Levei Agreement (SLA) as a control mechanism to assure such quality of service. However, there is a lack of formalized statements regarding the specification of these agreements. As a matter of contribution for the compreension of the SLA for ASP, this work introduces an exploratory research of the concep of SLA for ASP, and of the quality models and quality metrics to be considered by the SLA to assure the quality of the services provided.

Cette thèse vise à analyser l’interaction des procédés d’enseignement et d’appropriation dans un univers didactique multipolaire [le tuteur, les aides en ligne, les conduites d’auto-apprentissage, etc.], afin de déterminer à quelles conditions l’utilisation d’un environnement mixte rend possible la mise en oeuvre d’expériences d’apprentissage potentiellement favorables à l’acquisition de l’anglais langue étrangère auprès d’un public LANSAD en milieu universitaire. L’ouverture de cette thèse est consacrée à l’apprenant. Etant donné que la mise en place d’un dispositif pédagogique donné revient à mettre à la disposition de ce dernier des outils visant potentiellement à le conduire vers une progression qualitative et quantitative en L-C 2, celui-ci y occupe une place centrale en tant qu’utilisateur. La deuxième partie vise à mettre en évidence comment les logiques de la DLC et de la RAL peuvent être conciliées pour transformer les diverses implications et pédagogiques tirées de la première partie en outils didactiques susceptibles d’influer positivement sur les mécanismes acquisitionnels des apprenants. Ces considérations sont réinvesties dans le cadre de la troisième partie, afin d’étudier à quelle[s] condition[s] un dispositif permettant a priori aux apprenants [ou d’élaborer à leur intention] des tâches [macrotâches] qui répliquent ou simulent les pratiques sociales observées et qui servent d’objectifs aux apprenants ou à l’institution [Demaizière et Narcy-Combes, 2005] peut être mis en place. Enfin, les pratiques apprenantes au sein du dispositif élaboré sont analysées à la lumière des conclusions tirées dans nos trois premières parties. / The perspective of this dissertation is to analyze how the teaching and learning processes are interacting in a multipolar environment [tutor, online help, learning strategies] in order to shed light on the conditions to which a numerical environment is liable to promote English as a foreign language and culture [hereinafter L-C 2] acquisition amongst ESP learners at university level. The first part of the dissertation deals with the learner. If the implementation of a pedagogical environment aims at providing him - her with tools enabling both a potential qualitative and quantitative progression in L-C 2, the learner indeed plays a central role within it, as a user. In order to achieve this objective, a reflection on the L-C 2 learning processes is necessary to take them into account, as far as possible, in the setting up of a pedagogical environment. The second part looks at how the considerations of SLA, second language learning and teaching and the pedagogical implications drawn from the first part can be linked up and turned into tailor-made tools liable to impact positively on the learners’ SLA processes. The third part is about pedagogical engineering with a particular emphasis on how both the pedagogical implications drawn from the first two parts and the various parameters inherent to a pedagogical setting can be taken into account to implement an L-C 2 blended learning environment. Eventually, action research is presented. This part aims at providing an analysis of the learning practices and of the multipolar interaction taking place within a blended environment and at assessing its potential in terms of SLA.

Existing research on phrasal verbs is ample due to their prevalent existence in the English language and the difficulties they bring out as a result of their lack of transparency (Liu, 2011, p. 661). However, more research is necessary to cover new generations of English learners who cross paths with phrasal verbs. This study will provide empirical information on (i) whether Swedish students in 7th -9 th grade understand frequently used phrasal verbs better than nonfrequent ones, (ii) if phrasal verbs are easier to understand in productive- or perceptive tasks, (iii) if the students’ first languages (L1) interfere with this understanding, or (iv) if there is a difference in understanding phrasal verbs which are more common in AmE or BrE. The factors of second language acquisition taken into account in the analysis are explicit and implicit exposure of English, English varieties, crosslinguistic influences and idiomaticity. Chameliec & Weiss (2008, p. 381) define a phrasal verb as “a simple verb combined with an adverb or a preposition, or sometimes both, to make a new verb with a meaning that is different from that of the simple verb, e.g., go in for, win over, blow up”. The data was elicited with a questionnaire in three parts: one part about the participants background information and two parts on phrasal verb understanding, both in contextualized examples and without context. In the analysis, factors such as the construction of the questionnaire and choice of phrasal verbs need to be considered. The results demonstrate that Swedish junior high school students understand about 50% of the tested phrasal verbs in both parts of the questionnaire. More frequent ones are easier to understand, more so the AmE PVs, and the perceptive task generated a slightly higher percentage of correct answers. The textbooks did not have explicit sections on phrasal verbs, or even formulaic expressions in general. However, the books contained vocabulary boxes with a few different phrasal verbs, which also occurred in the texts. Since no explicit teaching method has been applied in these classes, doing so might increase the general frequency of correct answers. Furthermore, no conclusive results can be made regarding crosslinguistic influences, however, hypotheses on positive transfer can be made.

La dynamique professionnelle pour améliorer la qualité du soin montre qu’en dépit des progrès de l’enseignement sur la relation Soigné-Soignant, le temps du verbe médical est encore sacrifié au chevet des Malades. Depuis une vingtaine d’années, en neurologie, l’annonce diagnostique, ce faire-savoir, a surtout été analysée dans le registre des maladies avec atteinte cognitive. Ce travail de thèse se propose d’étudier, d’un point de vue épistémologique, philosophique, et éthique, le conflit des libertés en jeu lors de l’annonce diagnostique d’une maladie incurable paralysante évolutive telle que la Sclérose Latérale Amyotrophique (SLA). Guidée par la confrontation des vécus et des représentations recueillis auprès des Médecins des Centres SLA (38 entretiens), et à travers une enquête de terrain, des Patients et de leurs Proches, au moyen de questionnaires (203 questionnaires d’une quarantaine de questions), notre approche révèle que, dans l’impératif d’une information qui se veut avoir la vertu de conserver le plus longtemps possible l’autonomie du Patient, les angles de vulnérabilités du triangle relationnel Médecin-Patient-Proche s’affrontent dans une sous-estimation de la perception du Proche de son devoir d’engagement. Au travers d’une relecture philosophique des réponses des trois identités concernées, et d’une expérience professionnelle, nous comprenons que l’évolution rationnelle multidisciplinaire de la démarche de soin face à la maladie incurable transforme la clarté de l’information médicale en une injonction morale de présence du tiers. Parce qu’il s’agit d’impuissance, mais en aucun cas d’incapacité, nous proposons que tout Médecin, présent et à venir, apprenne à interroger en toute lucidité la pertinence de ses propositions de soins dés l’instant où il s’est engagé à annoncer l’incurabilité. Pour qu’un nouvel esprit du temps lui soit insufflé, quelle que soit son orientation, l’apprentissage systématique des soins palliatifs lui permettra de rester soucieux de ses choix, dans le clair-obscur des intentions humaines, et de reconnaître ses imperfections tout en se donnant le défi de la collaboration thérapeutique pour accompagner. / The teaching of Doctor-Patient relationship, in particular in making announcement of the diagnosis, makes progress in the Faculties of Medicine. But in practice, communicating the thruth of a disease with fatal issue remains a distressing time because still badly told. Amyotrophic Lateral Sclerosis, a motor neuron disease, is the most pejorative diagnosis to make in Neurology. In the controversy surrounding the time of the announcement of the diagnosis, and, by examining the results of 203 ALS Patients’ and their Caregivers’ questionnaires, we compare with the results of 38 ALS Centre Neurologists’ interviews. Through bringing an epistemological, ethical and philosophical analysis into focus, we argue that, in the rational multidisciplinary of the care in a rapid and incurable disease, the evolution of the clearly medical information changes the Doctor-Patient relationship into a moral injunction of presence for the Caregivers and the families. Only through the training of Doctors and a certain conception of Patient information in palliative care can the harmful consequences of such a trend be limited.

La sclérose latérale amyotrophique (SLA) est une pathologie neurodégénerative progressive se déclarant vers 50-60 ans. Elle est majoritairement de nature sporadique son incidence est estimée à 1 :1000. La SLA mène à une paralysie progressive et entraine généralement à la mort des patients de 2 à 5 ans suivant le diagnostic aux suite d’une fonte musculaire importante liée à la perte des neurones moteurs. Au cours des années, plusieurs mutations ont été identifiées autant chez les patients atteints de SLA sporadique que de SLA familiale. Ces mutations interfèrent avec la fonction de gènes variés, tels que DCTN1, codant pour la protéine dynactine1, sous-unité du complexe multimoléculaire dynactine. Ce complexe sert d’adaptateur au moteur moléculaire dynéine, chargé du transport axonal rétrograde, où sa fonction permettrait de régir l’activité du complexe moteur et sa capacité à lier divers cargos. Nous avons donc entrepris la caractérisation d’une lignée de poissons zèbre mutants pour dynactin1a (nommés mikre okom632, mokm632), plus particulière en terme du développement d’un type de neurone moteur primaire (les CaPs), afin de déterminer l’effet de la perte de fonction de ce gène sur l’axonogenèse, la formation et la stabilisation de la jonction neuromusculaire, sur le comportement de l’embryon, ainsi que sur le transport axonal.Nous suggérons que dynactin1 favorise la stabilité synaptique, où une perte de fonction de ce gène entraine des défauts de croissance, des anomalies éléctrophysiologiques et un comportement anormal. Ce rôle semble être indépendant des fonctions connues de régulateur du moteur dynéine. / Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease, which is mainly sporadic in nature. This progressive pathology has an estimated incidence of 1:1000 and generally leads to death within 2-5 years of diagnosis due to muscle wasting and severe motor neuron loss. Over the last years, mutations have been identified in both sporadic and familial ALS patients, interfering with the function of many genes, including DCTN1, which encodes for a subunit of the motor protein complex subunit dynactin. The dynactin complex serves as an adaptor for the dynein motor complex, responsible for retrograde axonal transport, and it is believed to regulate dynein activity and the binding capacity for cargos. We set out to characterize a mutant zebrafish line for dynactn1a (named mikre okom632, mokm632), looking specifically at caudal primary motor neurons (CaPs), with regard to axonal development, formation and stability of the neuromuscular junction (NMJ) and the behavioral phenotype produced in embryos, as well as axonal transport metrics. We suggest a role for dynactin1 in synapse stability, where the loss-of-function of this gene leads to growth defects, electrophysiological abnormalities and behavioral deficits. This role appears to be independent of its known function as a regulator of dynein, its implication in axonal transport, or its regulation of microtubule dynamics. With this study, we hope to elucidate key molecular mechanisms in ALS etiology by revealing the role of dynactin1 in NMJ development and maintenance.

Due to the fact that adolescents are familiar with so many different media and technology resources today, learning in a conventional way is no longer effective. The aim for this literature review was to analyse what research shows about the use of film as a teaching tool in English to develop students’ linguistic and critical thinking skills in upper secondary EFL classrooms. The results disclosed that film can improve students’ linguistic skills and critical thinking. One reason for this is that film is already such a large part of students’ lives and provides a meaningful and familiar context for them and that film offers visual support. Studentsʼ felt motivated to see and experience “real-life” situations as opposed to reading the conventional textbook. Interaction between the students also proved to be vital in developing their language skills. Results also showed that it is imperative that teachers present film not only as a tool of entertainment, but one for teaching as well. This can be done by creating contextualized assignments related to the film. The literature review concluded that there are gaps in knowledge of this subject and that further research is desirable.

本研究分析現有有關應用電腦於改善ESL教學之理論，這些理論目前係為了提供較易懂與靈活的人機介面。本研究同時對於在中國大陸與台灣在ESL教學上應用CAI（電腦輔助教學）有關的討論也予以分析。 本研究也試圖提出一套方法來找出並發展適台這些市場的CAI/ESL工具，而且可證實工具的有效性。此外，本研究並提出對設計這些工具非常關鍵的技術、文化、社會以及政治方面的考量。 最後，本研究提出了一個「E計畫」的產品說明及設計。E計畫為一種模組性的CAI多媒體系統，用於加強台灣大學生第一年英語教學。 / This paper analyses the existing theories underlying the application of computers to improve ESL education, theories which currently define the nature of interfaces designed to enhance access to and flexibility of computer-based information, and arguments for the application of computer-aided instruction to the problem of ESL education in the Chinese-language markets of Mainland China and Taiwan. The paper then attempts to outline a methodology for identifying, developing, and verifying the effectiveness of appropriate computer-assisted instructional ESL tools for these markets. Moreover, it outlines specific technological, cultural, social, and political issues critical to the design of such tools. Finally, it provides a product description and design for Project E, a modular CAI multimedia program aimed at enhancing ESL training for a first-year English course for English students at a Taiwanese university.

<p> <p>&nbsp / </p> </p> <p align="left">The underlying theme of this thesis is identification, classification, detection and prediction of cellular network faults using state of the art technologies, methods and algorithms.</p>

To facilitate the transition of Stereolithography (SLA) into the manufacturing domain and to increase its appeal to the micro manufacturing industry, process repeatability and surface finish need to be improved. Researchers have mostly focused on improving SLA surface finish within the capabilities of commercially available SLA machines. The capabilities of these machines are limited and a machine-specific approach for improving surface finish is based purely on empirical data. In order to improve surface finish of the SLA process, a more systematic approach that will incorporate process parameters is needed. To achieve this, the contribution of different laser and process parameters, such as laser beam angle, irradiance distribution, and scan speed, to SLA resolution and indirectly to surface finish, need to be quantified and incorporated into an analytical model. In response, a dynamic analytical SLA cure model has been developed. This model has been applied to SLA geometries of interest. Using flat surfaces, the efficacy of the model has been computationally and experimentally demonstrated. The model has been applied to process planning as a computational inverse design method by using parameter estimation techniques, where surface finish improvement on slanted surfaces has been achieved. The efficacy of this model and its improvement over the traditional cure models has been demonstrated computationally and experimentally. Based on the experimental results, use of the analytical model in process planning achieves an order of magnitude improvement in surface roughness average of SLA parts. The intellectual contributions of this research are the development of an analytical SLA cure model and the application of this model to process planning along with inverse design techniques for parameter estimation and subsequent surface finish improvement.