L’unité cellulaire du muscle squelettique est la myofibre, un syncytium hautement spécialisé générant la contraction musculaire. Au cours de la croissance et de la régénération musculaire, les cellules satellites quiescentes (cellules souches) du muscle squelettique adulte sont activées, prolifèrent puis fusionnent formant de nouvelles fibres. A l’aide d’un modèle murin de régénération et de cultures primaires, j’ai identifié TSHZ3 comme un nouveau marqueur des cellules satellites quiescentes et activées. Dans la lignée cellulaire C2C12, j’ai mis en évidence un effet répresseur spécifique de Tshz3 sur la différenciation myogénique. L’entrée des myoblastes dans la voie de différenciation terminale est déclenchée par le facteur Myogenin (MYOG). L’activation de la transcription du gène myogenin (Myog) est dépendante du facteur MYOD et fait intervenir le complexe de remodelage de la chromatine SWI/SNF. In vitro, TSHZ3 interagit avec BAF57 une sous unité du complexe SWI/SNF. TSHZ3 réprime l’activation dépendante de MYOD sur le promoteur proximal de Myog et cette répression dépend en partie de la présence de BAF57. L’activité répressive et la cinétique d’expression de Tshz3, indique que TSHZ3 pourrait empêcher l’activation prématurée du promoteur Myog lors de la prolifération des cellules satellites activées. TSHZ3 pourrait ainsi participer aux mécanismes de régulation permettant de contrôler l’équilibre entre prolifération, différenciation et renouvellement des progéniteurs myogéniques. / Skeletal muscles are made of several units called myofibers, a syncitium into which muscular contraction is generated. During the muscle growth and repair, the quiescent Satellite Cells (SCs; adult stem cells) become activated, proliferate and differentiate to form new multinucleated myofibers. In animal model and primary culture, I found that, Tshz3 was strongly expressed in the quiescent and activated satellite cells.In C2C12 myoblast cells, I showed a specific repressive effect of TSHZ3 on the myogenic differentiation. The terminal differentiation of the myoblastes is trigger by Myogenin (Myog). The transcriptional activation of Myog promoter involves MYOD and the SWI/SNF remodelling complex. In vitro, I showed that TSHZ3 interacts with BAF57, a subunit of the SWI/SNF complex. TSHZ3 represses the MYOD-dependant activation on the Myog promoter. This specific repression involves in part BAF57.The repressive activity of and the temporal dynamic of expression of Tshz3, indicated that TSHZ3 potentially is required to impede the premature activation of the Myog promotor during the SCs proliferation. These results suggest that TSHZ3 plays important roles in the molecular mechanisms operating in activated SCs when there are poised between proliferation, differentiation and self renewal of muscular progenitors.

Thesis advisor: Julie Mortimer / Essays on the effects of health policy payment systems in long-term care and end-of-life care institutions are studied. In the arena of long-term care, state Medicaid agencies have recently implemented pay-for-performance (P4P) programs to address poor quality of care in nursing homes. Using facility-quarter level data from 2003 to 2010, we evaluate the effects of Medicaid nursing home P4P programs on clinical quality measures, relying on variation in the timing of P4P implementation across states. Further, we exploit variation in the structure of states' programs to investigate whether programs that reward certain dimensions of quality are associated with larger improvements. We find P4P decreases the incidence of adverse clinical outcomes by as much as 8%, and the improvements are concentrated among the measures that experienced an increase in their relative returns and share strong commonalities in production. In the Hospice industry, changes to the current reimbursement system are mandated by the Patient Protection and Affordable Care Act. The motivation stems from noticeable hospice utilization changes since the Medicare Hospice Benefit (MHB) introduced a per-diem reimbursement in 1983. This research analyzes the abilities of a multi-tiered payment system, and a simpler two-part pricing system, to accurately match Medicare payments with hospice patient costs. Both systems improve on the current payment mechanism, while two-part pricing is the only system to maintain access to care for all MHB eligible patients. In addition, consumer disutility incurred by driving to airports is estimated and used to define air travel markets. Though an accurate definition of an economic market is important for any study of industry, there is no rule governing what exactly constitutes a market. To define a market we must ask the question ``between which products do consumers substitute,'' knowing that the answer to this question will depend on how ``close'' products are to one another in product space, as well as how close they are to one another, and to consumers, in geographic space. We estimate a discrete choice model of air travel demand that uses known information about the locations of products and consumers, which allows us to study substitution patterns among air travel products at different airports. We evaluate the commonly used city-pair and airport-pair definitions of a market for air travel, and conclude that a city-pair is the appropriate definition. We also employ the Hypothetical Monopolist test for antitrust market definition, as defined by the Department of Justice and Federal Trade Commission, and conclude that the relevant geographic market for antitrust analysis is frequently more narrowly defined as an airport-pair. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Economics.

Quando um país se torna auto-suficiente em uma parte do ciclo nuclear, quanto à produção de combustível que será usado em suas centrais nucleares para a geração de energia, precisa voltar sua atenção para a melhor forma de armazenar este combustível após a sua utilização. A armazenagem do combustível nuclear queimado é uma prática necessária e utilizada nos dias atuais em todo o mundo como temporária, tanto por países que não têm definido o plano de destinação final, isto é, o repositório definitivo, como também por aqueles que já o possuem. Existem dois aspectos principais que envolvem os combustíveis queimados: um referente à armazenagem do combustível nuclear queimado destinado ao reprocessamento e o outro ao que será enviado para deposição final quando o sítio de deposição definitiva estiver definido, corretamente localizado, adequadamente caracterizado quanto aos diversos aspectos técnicos, e licenciado. Este último aspecto pode envolver décadas de estudos por causa das definições técnicas e normativas em um dado país. No Brasil, o interesse está voltado para a armazenagem dos combustíveis queimados que não serão reprocessados. Este trabalho analisa os tipos possíveis de armazenagem, o panorama internacional e a possível proposta para a futura construção de um sítio de armazenagem temporária no país. / When a country becomes self-sufficient in part of the nuclear cycle, as production of fuel that will be used in nuclear power plants for energy generation, it is necessary to pay attention for the best method of storing the spent fuel. Temporary storage of spent nuclear fuel is a necessary practice and is applied nowadays all over the world, so much in countries that have not been defined their plan for a definitive repository, as well for those that already put in practice such storage form. There are two main aspects that involve the spent fuels: one regarding the spent nuclear fuel storage intended to reprocessing and the other in which the spent fuel will be sent for final deposition when the definitive place is defined, correctly located, appropriately characterized as to several technical aspects, and licentiate. This last aspect can involve decades of studies because of the technical and normative definitions at a given country. In Brazil, the interest is linked with the storage of spent fuels that won't be reprocessed. This work analyses possible types of storage, the international panorama and a proposal for future construction of a spent nuclear fuel temporary storage place in the country.

O combustível nuclear queimado (CNQ) é retirado do reator nuclear após exaurir sua eficiência de geração de energia. Após ser retirado do reator, esse combustível é temporariamente armazenado em piscinas com água na própria instalação do reator. Durante esse tempo, o calor gerado e os elementos radioativos presentes, de meia-vida média e curta, caem até níveis que permitem retirar o combustível queimado da piscina e enviá-lo para depósitos temporários de via seca. Nessa fase, o material precisa ser armazenado segura e eficazmente de forma que possa ser recuperado em futuro próximo, ou disposto como rejeito radioativo. A quantidade de combustível queimado cresce anualmente e, nos próximos anos, vai aumentar mais ainda por causa da construção de novas instalações de geração de energia de origem nuclear. Nos dias de hoje, o número de instalações novas voltou a atingir os níveis da década de 1970, porque é maior que a quantidade de ações de descomissionamento de instalações antigas. Antes que seja tomada qualquer decisão, seja a de recuperar o combustível remanescente ou considerar o CNQ como rejeito radioativo, o mesmo precisa ser isolado em um dos diferentes tipos de armazenagem existentes no mundo. No presente estudo mostra-se que a armazenagem do CNQ, via seca, em cascos é a opção mais vantajosa. Propõe-se um modelo de casco autóctone para combustível de reatores de potência e de uma instalação de armazenagem para abrigar esses cascos. É um estudo multidisciplinar no qual foi desenvolvida a parte conceitual de engenharia e que poderá ser usada para que o CNQ nacional, retirado dos reatores brasileiros de potência, seja armazenado com segurança por um longo período até que as autoridades brasileiras decidam o local para deposição final. / Spent nuclear fuel (SNF) is removed from the nuclear reactor after the depletion on efficiency in generating energy. After the withdrawal from the reactor core, the SNF is temporarily stored in pools at the same site of the reactor. At this time, the generated heat and the short and medium lived radioactive elements decay to levels that allow removing SNF from the pool and sending it to temporary dry storage. In that phase, the fuel needs to be safely and efficiently stored, and then, it can be retrieved in a future, or can be disposed as radioactive waste. The amount of spent fuel increases annually and, in the next years, will still increase more, because of the construction of new nuclear plants. Today, the number of new facilities back up to levels of the 1970s, since it is greater than the amount of decommissioning in old installations. As no final decision on the back-end of the nuclear fuel cycle is foreseen in the near future in Brazil, either to recover the SNF or to consider it as radioactive waste, this material has to be isolated in some type of storage model existing around the world. In the present study it is shown that dry SNF storage is the best option. A national cask model for SNF as well these casks storage installation are proposed. It is a multidisciplinary study in which the engineering conceptual task was developed and may be applied to national SNF removed from the Brazilian power reactors, to be safely stored for a long time until the Brazilian authorities will decide about the site for final disposal.

O combustível nuclear queimado (CNQ) é retirado do reator nuclear após exaurir sua eficiência de geração de energia. Após ser retirado do reator, esse combustível é temporariamente armazenado em piscinas com água na própria instalação do reator. Durante esse tempo, o calor gerado e os elementos radioativos presentes, de meia-vida média e curta, caem até níveis que permitem retirar o combustível queimado da piscina e enviá-lo para depósitos temporários de via seca. Nessa fase, o material precisa ser armazenado segura e eficazmente de forma que possa ser recuperado em futuro próximo, ou disposto como rejeito radioativo. A quantidade de combustível queimado cresce anualmente e, nos próximos anos, vai aumentar mais ainda por causa da construção de novas instalações de geração de energia de origem nuclear. Nos dias de hoje, o número de instalações novas voltou a atingir os níveis da década de 1970, porque é maior que a quantidade de ações de descomissionamento de instalações antigas. Antes que seja tomada qualquer decisão, seja a de recuperar o combustível remanescente ou considerar o CNQ como rejeito radioativo, o mesmo precisa ser isolado em um dos diferentes tipos de armazenagem existentes no mundo. No presente estudo mostra-se que a armazenagem do CNQ, via seca, em cascos é a opção mais vantajosa. Propõe-se um modelo de casco autóctone para combustível de reatores de potência e de uma instalação de armazenagem para abrigar esses cascos. É um estudo multidisciplinar no qual foi desenvolvida a parte conceitual de engenharia e que poderá ser usada para que o CNQ nacional, retirado dos reatores brasileiros de potência, seja armazenado com segurança por um longo período até que as autoridades brasileiras decidam o local para deposição final. / Spent nuclear fuel (SNF) is removed from the nuclear reactor after the depletion on efficiency in generating energy. After the withdrawal from the reactor core, the SNF is temporarily stored in pools at the same site of the reactor. At this time, the generated heat and the short and medium lived radioactive elements decay to levels that allow removing SNF from the pool and sending it to temporary dry storage. In that phase, the fuel needs to be safely and efficiently stored, and then, it can be retrieved in a future, or can be disposed as radioactive waste. The amount of spent fuel increases annually and, in the next years, will still increase more, because of the construction of new nuclear plants. Today, the number of new facilities back up to levels of the 1970s, since it is greater than the amount of decommissioning in old installations. As no final decision on the back-end of the nuclear fuel cycle is foreseen in the near future in Brazil, either to recover the SNF or to consider it as radioactive waste, this material has to be isolated in some type of storage model existing around the world. In the present study it is shown that dry SNF storage is the best option. A national cask model for SNF as well these casks storage installation are proposed. It is a multidisciplinary study in which the engineering conceptual task was developed and may be applied to national SNF removed from the Brazilian power reactors, to be safely stored for a long time until the Brazilian authorities will decide about the site for final disposal.

Quando um país se torna auto-suficiente em uma parte do ciclo nuclear, quanto à produção de combustível que será usado em suas centrais nucleares para a geração de energia, precisa voltar sua atenção para a melhor forma de armazenar este combustível após a sua utilização. A armazenagem do combustível nuclear queimado é uma prática necessária e utilizada nos dias atuais em todo o mundo como temporária, tanto por países que não têm definido o plano de destinação final, isto é, o repositório definitivo, como também por aqueles que já o possuem. Existem dois aspectos principais que envolvem os combustíveis queimados: um referente à armazenagem do combustível nuclear queimado destinado ao reprocessamento e o outro ao que será enviado para deposição final quando o sítio de deposição definitiva estiver definido, corretamente localizado, adequadamente caracterizado quanto aos diversos aspectos técnicos, e licenciado. Este último aspecto pode envolver décadas de estudos por causa das definições técnicas e normativas em um dado país. No Brasil, o interesse está voltado para a armazenagem dos combustíveis queimados que não serão reprocessados. Este trabalho analisa os tipos possíveis de armazenagem, o panorama internacional e a possível proposta para a futura construção de um sítio de armazenagem temporária no país. / When a country becomes self-sufficient in part of the nuclear cycle, as production of fuel that will be used in nuclear power plants for energy generation, it is necessary to pay attention for the best method of storing the spent fuel. Temporary storage of spent nuclear fuel is a necessary practice and is applied nowadays all over the world, so much in countries that have not been defined their plan for a definitive repository, as well for those that already put in practice such storage form. There are two main aspects that involve the spent fuels: one regarding the spent nuclear fuel storage intended to reprocessing and the other in which the spent fuel will be sent for final deposition when the definitive place is defined, correctly located, appropriately characterized as to several technical aspects, and licentiate. This last aspect can involve decades of studies because of the technical and normative definitions at a given country. In Brazil, the interest is linked with the storage of spent fuels that won't be reprocessed. This work analyses possible types of storage, the international panorama and a proposal for future construction of a spent nuclear fuel temporary storage place in the country.

In the United States, congestive heart failure (CHF) is a cardiac condition with increasing hospitalization and rehospitalization burden to patients, families, and the healthcare system. This chronic condition is expected to affect more than 8 million people by 2030; however, not much is known about the relationship between risk factors and hospital readmissions once CHF patients are discharged to a skilled nursing facility (SNF). Applying a systems theory unbounded systems thinking, coupled with a systems-thinking approach the purpose of this quantitative, retrospective cohort study was to examine CHF hospital readmissions from SNFs within a 90-day period using a secondary data set of gender, age, race, SNF geographic location, length of SNF stay, and home health use risk factors. A binary logistic regression analysis revealed that out of 238 episodes, 99 patients were readmitted; however, no statistically significant relationship between the risk factors and readmission was found. Findings suggest that CHF readmissions from the SNF are not attributed to only quantifiable risk factors. Based on these findings, further research can support social change through multifaceted quantitative and qualitative systemic analyses to identify and inform how healthcare organizations can better assist the elderly population with CHF and improve future post-acute community-based health education and prevention programs.

Readmission of skilled nursing facility (SNF) residents has become a financial and quality-of-care concern for facility leaders. SNF administrators do not know whether nurse staffing levels are impacting readmission rates. The Affordable Care Act included measures to monitor and improve quality and to penalize SNFs that have high readmission rates. The purpose of this quantitative correlational study was to examine the relationship between SNF nurse staffing levels and readmission rates using the Skilled Nursing Facility Readmission Measure (SNF RM). The theoretical framework for the study was Donabedian's structure, process, outcome model. The research questions addressed the relationship between nurse staffing levels and rehospitalization percentages for SNFs, and the relationship between RN staffing levels and rehospitalization percentages. A quantitative methodology was used to analyze publicly reported secondary data from Centers for Medicare and Medicaid Services staffing files and SNF Value-Based Purchasing (SNF VBP) program data. Pearson's correlation was used to examine the relationship and strength between nurse staffing levels and the SNF RM. The sample included 374 SNFs across Georgia that participated in the SNF VBP program. Findings from the multiple regression analysis and analysis of variance indicated no statistically significant relationship between nurse staffing levels and SNF RM rates. Facility characteristics across Georgia showed some variations in staffing levels and SNF RM rates. Findings promote positive social change by providing SNF leaders with needed information to make decisions about staffing needs when considering staffing above the state averages. Health care leaders and policymakers might use the findings when considering recommendations for staffing regulations.

L'organisation de l'ADN sous forme de nucléosome interfère avec différents processus cellulaires. La cellule recrute des facteurs de remodelage et des variants d'histones pour surmonter cette barrière physique. Dans ce travail, nous utilisons la Microscopie à Force Atomique pour visualiser des mono- et des oligo- nucléosomes à l'équilibre et hors-équilibre.<br />Nous montrons que le variant H2A.Bbd modifie la structure et la dynamique du mono-nucléosome et que sa présence altère la faculté de la chromatine à former une structure d'ordre supérieur. En utilisant un modèle physique nous expliquons quantitativement ce comportement par la flexibilité du mono-nucléosome.<br />Nous étudions ensuite le mécanisme du remodelage de mono-nucléosomes par SWI/SNF et RSC. Nous mettons en évidence un intermédiaire réactionnel sous la forme d'un nucléosome sur-complexé apparaissant avant le nucléosome glissé. Enfin au niveau des di-nucléosomes nous montrons que RSC est un ‘randomiseur' processif et séquentiel.

<p>Cultivable land is a limited resource and agriculture contributes to some of the most serious environmental problems facing the planet like, global warming, eutrophication and loss of biodiversity. The specialized, industrial agriculture with monoculture and extensive input of external energy, commercial fertilizer, and chemical pesticides are all essentially unsustainable. An adaptation to other methods of production is necessary to preserve the environment for future generations. The aim of this study is to describe the factors that distinguish sustainable from unsustainable agriculture. The results will be used to examine if and how the European Union (EU) works in order to create a more sustainable agricultural industry and to analyze the preconditions for such development. We have used a method based on abduction and we have a hermeneutic and ecological economic approach. The empirical survey is of a qualitative nature and is based on four interviews and literature studies. The results of this study shows that a sustainable agriculture should be build on ecological premises, which is easier to achieve in small-scale, functional, integrated and cycle-based farming. Modern farming’s dependence of fossil fuel and pesticides and the excess use of land must cease. Furthermore, there is an urgent need to decrease our consumption of meat products. EU’s agricultural policy is based on a worldview that relies on production optimization and is growth-oriented and these approaches must be changed. Certain positive changes have occurred within EU, but the decision-making process is slow and bureaucratic. Financially strong lobbyists have too much influence and power, compared to the rest of society. This makes it difficult to work for change and attain actual sustainability.</p>