L’ataxie de Friedreich (AF) est une maladie neurodégénérative à transmission autosomique récessive. Cette pathologie se caractérise par une dégénérescence spinocérébelleuse, une cardiomyopathie hypertrophique qui est la cause majeure du décès des patients, et un risque accru de diabète. La mutation majoritaire causant l’AF est une hyper-expansion de triplet GAA dans le premier intron du gène FXN codant la frataxine, une protéine mitochondriale ubiquitaire codée par le génome nucléaire. Ces hyper-expansions instables conduisent à une inhibition de la transcription du gène FXN et donc à une baisse d’expression de la frataxine. Aucun traitement curatif n’est disponible à l’heure actuelle pour cette maladie. Seule une meilleure compréhension de la physiopathologie de l’AF permettra d’envisager le développement de stratégies thérapeutiques efficaces. Plusieurs travaux montrent que la frataxine intervient dans la biosynthèse des centres Fe-S, mais son rôle exact dans cette voie, et sa possible contribution dans d’autres processus biochimiques, doivent encore être élucidés. Par une approche de protéomique quantitative utilisée pour la première fois sur des lignées lymphocytaires issues d’un patient AF et d’un individu non atteint, nous avons pu établir le profil d’expression des protéines associées à un déficit en frataxine. Ces nouvelles données confirment les processus altérés décrits pour l’AF, et ont permis la mise en exergue de nouveaux mécanismes mitochondriaux impactés, comme l’altération de la voie d’importation via CHCHD4. La mitochondrie interagissant avec le réticulum endoplasmique (RE), nous avons analysé et comparé l’impact d’un stress induit par la thapsigargine ciblant le RE sur le profil d’expression des protéines des lymphocytes B AF et contrôles. Ces analyses montrent que le déficit en frataxine rend les mitochondries des cellules de patients AF plus sensibles à un stress du RE, nécessitant la mise en place de réponses adaptatives spécifiques. L’approfondissement des mécanismes altérés associés au déficit en frataxine, avec et sans stress exogène, permettront d’une part, de mieux comprendre la pathogenèse de l’AF et d’autre part, de proposer des stratégies thérapeutiques adaptées. / Friedreich’s ataxia (FRDA) represents the most frequent type of autosomal-recessively inherited ataxia associated with a cardiomyopathy, which is the main cause of the death, and a risk of diabetes. FRDA is caused by mutations in the FXN gene, encoding mitochondrial frataxin, arising from an unstable hyperexpansion of GAA triplet repeats in the first intron of the gene. This hyperexpansion leads to FXN gene silencing and a quantitative decreased expression of frataxin. However despite many efforts to overcome any of these abnormalities, there is currently no efficient treatment to cure or even stop the progression of this disease, mostly because many aspects of the pathological consequences of frataxin depletion are still not fully understood. The precise role of frataxin is still under debate. A key function of frataxin in Fe-S cluster biogenesis has now been clearly pointed out, but how its role in this essential cellular pathway correlates with the pathophysiology of FRDA needs to be further investigated. To better understand the biochemical sequelae of frataxin reduction, global protein expression analysis was performed using quantitative proteomic experiments in Friedreich’s ataxia patient-derived B-lymphocytes as compared to controls. We were able to confirm a subset of changes in these cells and importantly, we observed previously unreported signatures of protein expression. Mitochondria are closed to endoplasmic reticulum (ER) and we used quantitative proteomic experiments to screen and analyze the impact of ER stress induced with thapsigargin in Friedreich’s ataxia patient-derived B-lymphocytes as compared to controls. We observed that the frataxin deficiency makes cells more sensitive to ER stress and leads to an up-regulation of specific adaptive mechanisms. The identification of a core set of proteins changing in the FRDA pathogenesis, with or without exogenous stress, is a useful tool in trying to decipher the function(s) of frataxin in order to clarify the metabolic disease process and find future targets for novel therapeutic strategies.

acase@tulane.edu / Abstract This research seeks to further the understanding of female microentrepreneurship as it is conceptualized and applied to initiatives that supporting women’s economic and social empowerment. Social norms, institutional discrimination, and gender constraints define the activities and persons that are entrepreneurial, thereby affecting female microenterprise motivations, characteristics, and success. In addition, contemporary microenterprise initiatives draw on women’s stereotypical caret-taking roles to justify their economic development, while female microenterprises remain distinguishable by their informality, small size, and low returns. The enterprises created through resource allocation programs, such as microcredit, are largely informal and home-based subsistence enterprises that offer a low-quality employment option to women and fail to challenge or expand existing gender constraints. Data from focus group participants and analysis of survey responses from 487 female microentrepreneurs in Kandy, Sri Lanka are used to compare female microentrepreneurial success in terms of both financial and empowerment outcomes. A novel conceptualization of the capabilities approach is presented and utilized to build an original analytical framework that redefines success in terms of women’s capabilities: whether female microentrepreneurship expands what they can be and do. An iterative approach to defining success outcomes establishes that adding empowerment indicators to definitions of success highlight different gender constraints to female microentrepreneurship than purely financial measures. Group differences provide an analysis of the gender constraints that are more prevalent among those meeting compound definitions of success and those who do not. A logistic regression of gender constraints, including personal household, and business characteristics, and women’s capabilities (as a proxy for empowerment), determines the impact of each constraint on the likelihood of being successful. The results suggest that, at the microenterprise level, female entrepreneurs are constrained by social and household norms that reduce their capabilities and enterprise success. Women’s hybrid entrepreneurial motivations, driven by their own economic and household considerations rather than outcomes desired by development initiatives, are established as offering fertile ground for future research, specifically regarding the impact of the household context. It is suggested that the motivations are distinct from those of women operating larger SMEs and require specific attention / 1 / Melissa E Langworthy

This thesis is about developing a recovery ethos for psychiatric services in New Zealand. The argument of the thesis is that currently a procedural ethos is dominant in psychiatric services in New Zealand, based on eclectic ways of facilitating recovery. Recovery from mental illness, is based on the criteria of symptom reduction and functioning and can be further refined to have a client and professional perspective. Rather than using an eclectic approach to facilitating recovery the thesis argues for a pluralistic approach, where the virtues, the relationship with professionals, client narrative and the psychiatric community become central to decision making, rather than principle based procedures. The thesis is an argued, applied philosophical thesis in terms of methodology. The scope of the thesis is psychiatric services and the focus is broadly ethical decision making. There are three main divisions to the thesis. Part 1 is concerned with clarification of the main terms used in the thesis. This involves exploring the historical background to the concept of recovery, clarifying the concept of recovery itself and providing an argument for giving greater prominence to the term mental illness over the term mental disorder. Part 2 identifies the main problem of the thesis, namely the procedural ethos, and the problems it is causing clients suffering from mental illness in facilitating their recovery. Part 3 shows what is involved in developing a recovery ethos for psychiatric services in New Zealand.

The current population in Ho Chi Minh City (HCMC) is more than 7 million. Due to pressures of increasing population, the developing economy and climate change, the future security of water supply is far from satisfactory. There is also pressure to connect a large number of customers currently not connected to the HCMC water supply reticulation grid. Current water resources management tends to be fragmented and focused purely on supply side management. It is not economically and environmentally sustainable to focus purely on augmenting supply to meet increasing demand. Sustainable water resources management requires a broader more holistic approach. Government's plans to improve current and future water management issues are examined in the context of two case studies, one from Australia (a developed country) and one from the Philippines (a developing country). The sustainable water management approaches adopted by these two case studies sit at either end of the s pectrum of options. One is closer to a centralized government planning model and the other is a more radical privatisation flavoured model. The thesis investigates the current water demand and supply balance for residential, commercial and industry; and propose a balanced strategy to meet the HCMC's demand until year 2020. The amount of water savings are calculated by implementing a suite of water conservation initiatives. The proposed initatives will substantially narrow the gap between the planned supply and forecasted demand, thus providing a acceptable reasonable supply security for the community.

Thesis (M. Ed.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

<p>Background: Today, an increased need to value patents is expressed in several different situations. For example, banks more frequently accept patents as collateral for loans and patents are being exchanged more often between companies. It is argued that a hindrance for the recognition of the value of patents, and other assets lacking physical form, is that the current methods of valuation are not developed for this type of assets. </p><p>Purpose: Our objective is to investigate the practical relevance of four theoretical valuation approaches in the context of patent valuation and to point out crucial factors affecting the choice of valuation approach. </p><p>Procedure: Interviews were conducted with professionals working in the field of corporate finance and with an expert in the field of patents and intellectual property rights. </p><p>Results: The respondents are not of the same opinion whether relevant approaches for patent valuation exist at all. Among the respondents who find it possible to value patents, the income approach is the dominating approach. The theoretical correctness of this approach, derived from the definition of value, is stressed as the primary argument for the use of it. Methods such as Decision Tree Analysis, within the income approach, and Relief from Royalty, a hybrid of the market- and income approach, are used as complements.</p>

Background: Today, an increased need to value patents is expressed in several different situations. For example, banks more frequently accept patents as collateral for loans and patents are being exchanged more often between companies. It is argued that a hindrance for the recognition of the value of patents, and other assets lacking physical form, is that the current methods of valuation are not developed for this type of assets. Purpose: Our objective is to investigate the practical relevance of four theoretical valuation approaches in the context of patent valuation and to point out crucial factors affecting the choice of valuation approach. Procedure: Interviews were conducted with professionals working in the field of corporate finance and with an expert in the field of patents and intellectual property rights. Results: The respondents are not of the same opinion whether relevant approaches for patent valuation exist at all. Among the respondents who find it possible to value patents, the income approach is the dominating approach. The theoretical correctness of this approach, derived from the definition of value, is stressed as the primary argument for the use of it. Methods such as Decision Tree Analysis, within the income approach, and Relief from Royalty, a hybrid of the market- and income approach, are used as complements.

The aim of this study was to, on the basis of normalization and autonomy; investigate how staff working in group homes discusses about sexuality of people with an intellectual disability. Our study was based on ten semi-structured interviews of both care staff and heads of group homes to get responses from different levels within the same organization. The empirical material was analyzed through the theory of social constructivism, which focuses on how we construct the world through interaction and language, and the normalization principle whose goal is that all people with developmental disabilities should have the opportunity to live like all other people. We view these theories as useful to gain understanding of the questions in our study. The result of this study showed that the subject only comes up for discussion when problems arise, that the communication on the subject is inadequate and more discussion is requested. Further the result illustrated that staff strives for people with developmental disabilities to feel they have autonomy but this is also a challenge in their work.

Thesis (Ed. D.)--Lehigh University, 2000. / Includes vita. Includes bibliographical references (leaves 162-175).

Thesis--PlanB (M.S.)--University of Wisconsin--Stout, 2003. / Includes bibliographical references.