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Rôles normal et pathologique des phosphorylations de la huntingtine par Cdk5 / Physiological Functions of Huntingtin Phosphorylations at Serines 1181/1201 by Cdk5 in Health and DiseaseBen M'Barek, Karim 26 November 2012 (has links)
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.
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Impacts de l'orientation entrepreneuriale sur la performance-export des PME Togolaises à vocation internationale. / Impact of the entrepreneurial orientation on the export performance of Togolese SMEs with an international vocation.Kombate, Kangnaguidjoa 15 June 2018 (has links)
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.
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Entrepreneurial learning, opportunity recognition and development - Evaluating the impact of a training programme at TSiBA Education, Cape Town, South AfricaSamsodien, Adeeb January 2017 (has links)
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.
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Gestão de marketing em um contexto de demandas divergentes entre stakeholders: um estudo exploratório / Marketing management in a context of divergent stakeholders\' demands: an exploratory studyNogueira, Bárbara Miklasevicius 29 September 2014 (has links)
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.
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Controlled drug release from oriented biodegradable polymersAmbardekar, Rohan January 2015 (has links)
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.
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1096 |
Patientenorientierung als QualitätsmerkmalBleses, Helma 25 January 2005 (has links)
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.
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Orientation-Marché: Une stratégie pertinente pour la gestion des institutions d'enseignement supérieur?/Is market orientation a relevant strategy for the management of Higher educational institutions?Bugandwa Mungu Akonkwa, Deogratias D. 07 November 2008 (has links)
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.
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Kundanpassad returhantering : E-handelsföretag och deras kunder, en studie om klädbranschen / Customized returns management : E-commerce companies and their customers, a studie of the retail industryEdman, Anna, Marklinder, Johanna January 2015 (has links)
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.
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Kostvanor som har betydelse för karies : en jämförelse mellan elever vid yrkesinriktade och högskoleförberedande gymnasieprogramPezoa, Marcello January 2014 (has links)
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.
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1100 |
The Influence Of Thematic Instruction On The Motivation Of Upper-intermediate Preparatory School Students Of English For Academic Purposes (eap) At MetuOlgun, Alison Alev 01 June 2004 (has links) (PDF)
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.
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