La mutation à l’origine de la maladie de Huntington (MH) correspond à une expansion anormale de glutamines sur la protéine huntingtine (HTT). La MH est caractérisée par des symptômes moteurs et cognitifs mais également des troubles psychiatriques tels que l’anxiété et la dépression.Au cours de ma thèse, j’ai montré que la HTT module le statut anxio-dépressif de la souris via ses phosphorylations aux sérines 1181/1201. En effet, l’ablation des phosphorylations sur la HTT endogène améliore significativement le phénotype anxio-dépressif de la souris. Chez la souris, cette modulation dépend d’une augmentation de la maturation et de la survie des nouveaux neurones dans l’hippocampe. En effet, l’irradiation focale de l’hippocampe, dans un contexte où les phosphorylations sont absentes, supprime la neurogenèse et la réduction du statut anxio-dépressif observée en l’absence de phosphorylations. Au niveau moléculaire, la HTT non phosphorylée accroît l’association des moteurs moléculaires et des vésicules de BDNF sur les microtubules, ce qui augmente les dynamiques et la libération du BDNF. Ceci active la voie de signalisation MAPK/CREB dans l’hippocampe, cette voie pouvant ainsi stimuler la neurogenèse.J’ai ensuite étudié le rôle de ces phosphorylations dans un contexte MH et j’ai démontré l’effet anxiolytique/antidépresseur de l’absence de ces phosphorylations.J’ai également montré le rôle de ces phosphorylations de la HTT au cours du développement du cortex embryonnaire.Les résultats obtenus au cours de ma thèse suggèrent que les mécanismes fondamentaux de neurogenèse sont régulés par la HTT et ses phosphorylations. De plus, ils identifient une nouvelle voie de modulation de l’anxiété/dépression faisant intervenir la HTT. / Huntington disease (HD) is a fatal neurodegenerative disorder associated with early psychiatric symptoms including anxiety and depression.During my thesis, I have demonstrated that huntingtin, the protein mutated in HD, modulates anxiety/depression-related behaviors through its phosphorylations at serines 1181 and 1201. Indeed, genetic phospho-ablation at serines 1181 and 1201 in mouse reduces basal levels of anxiety/depression-like behaviors in mouse. Suppression of neurogenesis by focal hippocampal irradiation abolishes this reduction of basal levels of anxiety/depression on some behavioral test demonstrating that neurogenesis is involved in this process. Ablation of HTT phosphorylations may stimulate neurogenesis through BDNF transport, release and signaling.I have also shown that ablation of phosphorylations on HTT is sufficient to ameliorate the anxiety/depression-like behavior of a mouse model of HD, which develops a behavior indicative of depression–like state.I have finally explored the role of HTT phosphorylation at serines 1181 and 1201 during brain development. During early steps of cortical neurogenesis, I have shown that ablation of HTT phosphorylations affects the mitosis of cortical progenitors, the fate of newly generated cells and the migration of new neurons.The results obtained during my thesis support the notion that HTT regulates key molecular mechanisms during neurogenesis both in adult and embryo. It also supports the notion that huntingtin participates to anxiety and depression-like behavior with potential consequences for the etiology of mood disorders and anxiety/depression in HD.

L'objectif de cette recherche est d'évaluer l'impact du profil du dirigeant sur le niveau d'OE et l'influence de ce dernier sur la performance-export de la PME dans le contexte togolais. A cet effet, une analyse quantitative par la période de régression logistique auprès de 65 PME exportatrices montre que la vision stratégique, les compétences clés, les traits de personnalité du dirigeant et les caractéristiques de la PME affectent positivement l’orientation entrepreneuriale internationale et la performance-export. Ces résultats ont le mérite de confirmer le modèle conceptuel adapté de Miller/Friesen et celui de Covin/Slevin dans le cadre du Togo. / The objective of this research is to assess the impact of the CEO's profile on the EO level and its influence on the export performance of the SMBs in the togolese context. The results of a quantitative analysis by logistic regression led to 65 exporting SMBs to this purpose, show that the strategic vision, the key competences, the CEO's traits of personality and the SMBs characteristics, are positively related to to the international entrepreneurial orientation (IEO) and to the export performance. These results have the merit of confirming the conceptual model adapted from M/F and the one of C/S within the Togolese framework.

Magister Commercii - MCom (Business and Finance) / The youth of South Africa is currently faced with high levels of unemployment and poverty. This raises concerns about the future of the South African people and its economy. Consequently, much is needed to develop the youth to allow for a prosperous future. A decrease in poverty and unemployment was found to be linked to an increase in education. Entrepreneurial education can have a significant impact on entrepreneurial success. This research paper aims to assess the influence of entrepreneurial education and training on students' entrepreneurial development. To ensure a comprehensive assessment of the development of students, I utilised a mixed methodology to assess students both quantitatively and qualitatively. The study assessed a sample of students from South Africa and the United States of America who jointly partook in a two-week entrepreneurial education and training programme at TSiBA Education, Cape Town, South Africa. Entrepreneurial education and training had a positive effect on the students' entrepreneurial development, entrepreneurial orientation and intentions to start a business. While entrepreneurial orientation aids the exploitation of business opportunities, before opportunities can be exploited they must be recognised. Bringing into question the link between students' entrepreneurial orientation and their abilities to recognise and develop opportunities into successful ventures. To explore this I interviewed two participants and found the high entrepreneurially orientated participant to exhibit greater opportunity recognition and development abilities, compared to the low entrepreneurially orientated participant. I concluded by finding that although differences do exist between high and low entrepreneurially orientated students, entrepreneurial education and training could positively influence students' entrepreneurial orientation and assist in the development of entrepreneurs. The results suggest that TSiBA Education should attempt to increase the duration of the entrepreneurial programme to maximize the influence of the entrepreneurial education and training.

A partir dos anos 1950, o conceito de marketing e a orientação para mercado destacaram a importância do consumidor para as empresas. Nas últimas décadas surgiu uma nova visão que propõe que as demandas de outros públicos também são relevantes, como colocam a orientação para stakeholders e a de marketing holístico, entre outras. Em alguns contextos, porém, consumidor e outros públicos têm demandas divergentes, como na indústria de alimentos brasileira atualmente. Se, por um lado, aumenta o consumo de industrializados, identifica-se que, por outro, o governo tenta mudar a composição desses alimentos para reduzir o teor de ingredientes considerados prejudiciais à saúde se consumidos em excesso e, assim como ONGs, tenta desestimular seu consumo. O presente estudo busca, por meio de uma pesquisa empírica, com amostra não-probabilística, analisar como é feita a gestão de marketing nesse contexto. Foram realizadas entrevistas semiestruturadas com sete gestores de marcas de alimentos industrializados que atuam em categorias onde o governo identifica necessidade de mudanças. O elemento de partida, por tangibilizar as decisões de gestão da marca e facilitar a abordagem do assunto, foi uma campanha de comunicação de marketing recente. As respostas foram analisadas pelo método de análise de conteúdo e os resultados indicam que, na gestão de marketing, as demandas do consumidor são as de maior relevância, até porque, sem colocá-las em evidência, há risco para o sucesso do negócio. Há algumas ações descritas pelos gestores que foram motivadas por pressões de outros públicos, como a mudança de público-alvo e de mensagem em campanhas de comunicação e a reformulação de produtos - neste último exemplo, porém, não houve adesão do mercado em dois casos narrados. Isso não significa, entretanto, que o consumidor não incorpore as discussões em torno da saudabilidade proposta por outros públicos e que, atualmente, evidenciam as demandas divergentes entre stakeholders. Um nicho, caracterizado principalmente pelo poder aquisitivo mais alto, tem interesses que vão ao encontro do que propõem o governo e as ONGs. O grande mercado consumidor, porém, ainda valoriza mais o acesso a novas categorias que se tornou possível com o recente aumento de renda no Brasil. O caminho para que as mudanças ocorram de maneira mais ampla e rápido, de acordo com os gestores, passa pela informação, de maneira a diminuir a divergência entre as demandas dos stakeholders envolvidos na questão. / In the 1950s, the marketing concept and the market orientation emphasized the importance of the consumer to companies. In the last decades, new concepts emerged, which highlight that the demand of other publics are also priorities, as state the stakeholder and the holistic marketing orientations, for example. In some contexts, however, consumers and other publics might have divergent demands, as in the Brazilian food industry nowadays. On one hand, the consumption of industrialized items increases and, on the other, government tries to change the formulation of those products to reduce the quantity of ingredients that are considered unhealthy if eaten in high levels and tries to discourage its consumption. Some NGOs are also dedicated to the subject and support the government\'s point of view. This study analyses the marketing management of brands in that context through an empirical research with a non-probability sample. In-depth interviews were conducted with seven marketing professionals of the food industry whose categories are involved in the discussions started by the Brazilian government. A recent marketing communication campaign was chosen as the starting point of the interview since it is a public expression of the brand and it could facilitate the conversation and analysis of the subject. The analytical procedure used was content analysis. The results show that consumers\' demands are the most relevant for marketing management because if the market is not satisfied, the business might be on risk. Some actions presented by the managers were motivated by pressure imposed by other publics, such as the change of the communication target for two brands and the implementation of new formulas for some products of other two brands. In these cases, however, the market did not accept the healthier options. Nevertheless, consumers are more aware of healthy habits. A niche of high-income people has demands that are closer to those presented by the government. But the average consumer, due to the recent income increase in Brazil, still places more value on having access to new categories than on making choices. In order for changes to happen faster and widely, bringing the consumers and government\'s demands closer, managers point out the need of information.

This research is the first systematic investigation of solid-state orientation as a novel method for controlling drug release from biodegradable polymers. The effect of various degrees of polymer orientation was studied in oriented Poly (L-lactic acid) (PLA) films containing curcumin and theophylline as model drugs. Additionally, direction specific drug release was studied from oriented PLA rods containing paracetamol. The films oriented to 2X uniaxial constant width (UCW) or 2X2Y biaxial draw ratio showed retardation of drug release, when their nematic structure was stabilised by the presence of crystalline theophylline. Contrarily, the same films when contained solid solution of curcumin, shrunk in the release medium and exhibited a release profile similar to the un-oriented films. All films oriented to the UCW draw ratio ≥ 3X contained α crystalline form of PLA and showed acceleration of drug release proportionate to the draw ratio. According to the proposed mechanism augmented formation of water filled channels in these films was responsible for faster drug release. Similarly, the paracetamol loaded PLA rods die-drawn to uniaxial draw ratios ≥ 3X exhibited enhancement of drug release. Importantly, the amount of drug released along the oriented chain axis was significantly larger than that in the perpendicular direction. Drug release from the die-drawn rods was accelerated by a greater degree than that observed from the oriented films. This can be correlated to the differences in their size, geometry and the crystalline form of PLA. In conclusion, the current study provided substantial evidence that solid-state orientation can offer a control over drug release from PLA.

Die Studie befasst sich mit der Klärung des Konzeptes der Patientenorientierung im Krankenhaus. Bei der Ausrichtung der betrieblichen Leistungen auf die Bedürfnisse der Kunden - oder genauer - Patienten sind für den Dienstleitungsbereich `Krankenhaus´ besondere Anforderungen zu beachten.Die Komplexität von Systemen der Leistungserbringung und die unterschiedlichen Interessen der an der Leistungserbringung beteiligten Anspruchsgruppen erfordert es, sowohl eine theoretische Konkretisierung vorzunehmen, als auch ein praktikables Instrument für die Erhebung und Beschreibung von Patientenorientierung in Krankenhäusern zu entwickeln. Die Studie weist messbare Indikatoren der Patientenorientierung aus und entwickelt hieraus ein Befragungsinstrument, dessen Güte durch Erhebungen in zwei Vergleichskrankenhäusern bestätigt werden konnte. Die Ergebnisse zeigen, dass Patientenorientierung von Patienten als Organisations- und Prozessqualität wahrgenommen und eingeschätzt wird.Patientenorientierung ist eine konkrete Forderung im Qualitätsmanagement und der Erfüllungsgrad dient als Qualitätsmerkmal in der Leistungserbringung. / The study sets a focus on the concept of patient orientation in hospitals and its economic and organizational impacts. The process of shifting the whole organization ‘hospital’ towards customers - or more precisely - patients` needs generates specific demands on management, quality of services and its structures.The complexity of the organization, the variety and divergence of interests involved call both for a theoretical clarification of the concept and the development of an instrument to describe and measure the degree of patient orientation in hospitals. The study revealed indicators for patient orientation and were used to develop a new questionnaire. The quality of that instrument was tested and confirmed in two German hospitals. The results showed that patients can recognize and estimate patient orientation as part of the hospitals management(organization) and process quality. Patient orientation has to be an important aspect of quality management and can be used as an indicator of organizational performance.

Market orientation is generally defined as the implementation of the marketing concept within organizations. It has been operationalized by such dimensions as customer orientation (the pursuit of customer satisfaction), Competitor Orientation, Inter-functional Coordination, and Responsiveness. According to a growing body of literature, this strategy is likely to help higher educational institutions in their effort overcome the challenges and pressures of their changing environment (these are: massification, professionalisation, budget constraints, the rise of stakeholders’ requirements in terms of quality control and accountability… In this research, I first object that those researchers who are suggesting market orientation as the suitable strategy have said nothing as for its content or definition. I also contend that empirical works using higher educational setting to operationalize the market orientation strategy are just conceptual transpositions, which do not consider the specificities of higher education institutions as compared to private firms. These shortcomings are the theoretical justification of my research. Hence, after showing the origin of the market orientation rhetoric in higher education, I develop a new conceptualization of the strategy and suggest a new scale for its measurement. The following dimensions composed my suggested scale: Stakeholder orientation (Students, policy-makers, and organizations), Competitor Orientation, Collaboration, Inter-functional Coordination, and Responsiveness. The empirical validation of these dimensions was enriched by a quantitative assessment of the place of the market orientation strategy within the mission statements of higher educational institutions. This research is one attempt in a whole ongoing trend towards research on how to relevantly import private sector strategies into public and nonprofit sector organizations, among which, higher education/ L'Orientation-Marché est généralement définie comme étant l'implémentation du marketing dans les organisations. Une revue de littérature permet de l’opérationnaliser par les dimensions telles que l'Orientation clients qui consiste en la poursuite de satisfaction des clients, Orientation concurrents, Coordination inter/intra fonctionnelle, et la Réponse organisationnelle. Cette stratégie est de plus en plus évoquée comme pouvant aider les institutions d'enseignement supérieur à faire face aux défis tels que la massification, la professionnalisation, la réduction des financements, la montée des exigences des parties prenantes en termes de qualité... Dans cette thèse, je constate d'une part que certains chercheurs se limitent à proposer cette stratégie sans en définir le contenu, et d'autre part que les travaux empiriques existants sur l'Orientation-Marché dans l'enseignement supérieur se limitent à des transpositions conceptuelles, sans tenir compte des spécificités des institutions d'enseignement supérieur. C'est pour cette raison qu'après avoir démontré l'origine des discours sur l'Orientation-marché dans ce secteur, je développe une échelle de mesure susceptible d'Opérationnaliser cette stratégie. L'échelle comprend l'Orientation vers les parties prenantes (Etudiants, Décideurs politiques, Entreprises), l'Orientation Concurrents, la Collaboration, la Coordination Interfonctionnelle, et la Réponse organisationnelle comme principales dimensions. La validation empirique de ces dimensions a été enrichie par une évaluation quantitative de la place de l'Orientation-Marché dans les missions des institutions d'enseignement supérieur, telles que déclarées dans leurs différents documents. Cette recherche est une première ébauche dans tout un courant de recherches sur l'importations des stratégies de gestion privée dans les institutions à but non lucratif.

Bakgrund: Majoriteten av e-handelsföretagen verksamma inom klädbranschen når inte lönsamhet vilket till viss del beror på den höga returandelen som i dagsläget ligger mellan 20-50 procent. Returandelen har ökat under de senaste åren och tros öka även i framtiden. Genom att minska sina returer med ett fåtal procent skulle e-handelsföretag kunna spara flera miljoner, dock kan kundlojaliteten gå förlorad om inte företaget möter kundens förväntningar gällande returhanteringen. Syfte: Syftet är att identifiera olika kunders returbeteenden för att förstå hur företagens returhantering kan anpassas till olika kundgrupper. Metod: I studien har författarna använt sig av en kvalitativ undersökningsmetod med ett hermeneutiskt förhållningssätt och tillämpat en explorativ samt deduktiv ansats. Resultat: Studien har identifierat två olika typer av kundgrupper med olika köp- och returbeteenden, således bör företagen segmentera kunderna utifrån dessa faktorer för att skapa en väl utförd returhantering. Företagen kan förbättra sin lönsamhet genom att kundanpassa sin returhantering eftersom en kundanpassad returhantering medför en ökad kundtillfredsställelse, ett ökat mervärde och en förbättrad kundlojalitet, vilket resulterar i en ökad lönsamhet hos företagen. / Background: The majority of the e-commerce companies in the retail industry are not profitable which is partly due to the high percentage of returned goods, which in the current situation is between 20-50 percent. In recent years the proportion of returned goods has increased and is also believed to increase in the future. By lowering the returns of goods with a few percent the e-commerce companies could save several millions, however customer loyalty can be lost unless the companies meets the customers’ expectations regarding the returns process. Purpose: The purpose is to identify the difference in customers’ returning behaviors in order to understand how companies' returns management can be adapted to different customer segmentations. Research method: The authors of the thesis have used a qualitative research method with a hermeneutic approach and applied both an explorative and a deductive approach. Results: The study has identified two different types of customer groups with different purchase and returns behaviors, thus companies should segment the customers based on these factors and the customers should be treated differently by the companies when it comes to returns management. The companies can improve their profitability by customizing their returns management because it generates greater customer satisfaction, increased added value and improved customer loyalty which results in increased profitability for the companies.

Studiens syfte var att undersöka skillnader i kostvanor som kan ha betydelse för utveckling av karies mellan ungdomar vid yrkesinriktade respektive högskoleförberedande gymnasieprogram. Datainsamling skedde vid två gymnasieskolor i södra Sverige med användning av en enkät som bestod av 32 frågor. Det skulle både finnas yrkesinriktade- och högskoleförberedande gymnasieprogram på de skolor som deltog. Sextio elever från respektive gymnasieinriktning skulle ingå i studien. Totalt erbjöds 143 elever >16 år att delta från två skolor. Resultatet baserades på 118 besvarade enkäter, 60 från de yrkesinriktade- och 58 från de högskoleförberedande gymnasieprogrammen. Individerna som studerade på högskoleförberedande gymnasieprogrammen åt i större utsträckning frukost (p=0.009) och skollunch dagligen (p=0.003) och handlade mer sällan i skolans kiosk eller närliggande livsmedelsbutik (p=0.000). De drack även kaffe med socker mer sällan under skoltid (p=0.006), drack juice eller saft mer sällan i hemmet (p=0.009) och åt chips eller ostbågar mer sällan i hemmet (p=0.044). Studiens slutsats är att det fanns skillnader mellan gymnasieelever vid de yrkesinriktade- och högskoleförberedande gymnasieprogram när det gäller frukost- och lunchvanor. Få skillnader fanns i övrigt mellan gymnasieeleverna vid de båda gymnasieinriktningarna avseende konsumtion av produkter som kan ha betydelse för karies. / The aim of this study was to examine differences in dietary habits that have significance for the development of caries between youths at professional- respectively higher educational preparatory high school programs. A survey with 32 questions was conducted at two high schools in southern Sweden. The schools should have hade professional- and higher educational preparatory high school programs. Sixty students from each high school orientation would be included in the study. A total of 143 students >16 yearswere invited to participate from two schools. The result is based on 118 answered surveys, 60 from the professional- and 58 from the higher educational preparatory high school programs. Individuals that studied at the higher educational preparatory high school programs ate in greater numbers breakfast (p=0.009) and school lunch (p=0.003) daily and shopped more rarely at the school kiosk or nearby grocery store (p=0.000). They also drank coffee with sugar more rarely under school time, (p=0.006), drank juice more rarely at home (p=0.009) and ate potato chips or cheese doodles more rarely at home (p=0.044).The conclusion of this study is that there were differences between high school students at the professional- and higher educational preparatory high school programs with regards to breakfast- and school lunch habits. Few differences existed otherwise between both high school orientations regarding consumption of products that could have significance for the development caries.

This research inquires into whether the motivation of students learning English for Academic Purposes (EAP) at the upper-intermediate level improves when thematic instruction is employed in the classroom. This is the first time that a theme-based integrated skills approach was implemented at the Department of Basic English (DBE), METU at the intermediate and upper-intermediate levels. With the outcome of the needs analysis carried out by the administration, it was realized that students at the preparatory school needed to use integrated skills as reflected in &lsquo / real life&rsquo / . Moreover, thematic instruction was seen to be a requisite in the new curriculum since content is a key motivating principle. Hence, since one of the main concerns was the motivation of students attending courses at the preparatory school, there was a need to examine whether using this mode of instruction at the upper-intermediate level was able to ameliorate student motivation. For this research, firstly a pilot study and then qualitative analysis using in-depth interviews developed on the basis of the pilot study was employed. Therefore, using a triangulation of different kinds of data on related questions, interviews were carried out with 14 students on three separate occasions at the end of each span from the upper-intermediate group, two administrators and six upper-intermediate instructors. From the point of view of the students it appeared that generally content encouraged learning and improved English proficiency if the themes/topics were found to be of interest. However, the degree of impact of the themes and topics on student motivation largely depended on whether the student was intrinsically motivated or not. If the student was intrinsically motivated, content had a nominal affect on motivating them. The study showed that if the themes are linear and have a parochial focus on topics, too much time is spent on a theme, a redundancy of lexical items are taught, unnecessary details are included, and difficult and academic language used, these led to student demotivation in respect of content. Thus, indicating a greater variety of content was needed.