La thèse est composée de trois parties. La première présente un certain nombre de mesures de dépendance extrême. Une application sur les actions et les obligations de 49 pays montre que la théorie des valeurs extrêmes multivariées conduit aux résultats différents de ceux issus du coefficient de corrélation, mais relativement proches de ceux obtenus du rho de Spearman conditionnel multivarié. Cette partie évalue aussi le risque de pertes importantes simultanées. La deuxième partie examine les déterminants des co-mouvements extrêmes entre 5 pays core et 49 pays non core. Les mécanismes de transmission des chocs varient de la période moins récente à la période récente, des pays développés aux pays émergents, des chocs normaux aux chocs extrêmes. La troisième partie étudie le rôle de valeur refuge de l’or sur la période 1986-2012. Les gains positifs extrêmes de l'or peuvent être liés aux pertes extrêmes du S&P. Cependant, ce lien n'est pas toujours valable, il évolue dans le temps et serait conditionné par d'autres facteurs. / The thesis consists of three parts. The first part introduces a number of measures of extreme dependency. An application on stock and bond markets of 49 countries shows the multivariate extreme value theory leads to results which are different from those from the correlation coefficient, but relatively close to those obtained from multivariate conditional Spearman's rho. This part also assesses the risk of simultaneous losses. The second part examines the determinants of extreme co-movements between 5 core countries and 49 non-core countries. Transmission mechanisms of shocks vary from less recent to recent period, from developed to emerging markets, from normal to extreme shocks. The third part examines the role of safe haven of gold over the period 1986-2012. Extreme positive gains of gold can be linked to extreme losses of S&P. However, this relationship is not always valid, it evolves over time and could be determined by other factors.

Cette thèse est composée de 3 essais. Le 1er essai traite de la problématique du risque de pertes extrêmes dans le secteur bancaire dans un contexte du problème d'agence entre les actionnaires et les top managers des banques. Pour pouvoir inciter les banques à ne pas prendre le risque de pertes extrêmes, il est proposé d'appliquer la régulation des fonds propres sous forme d'une politique de recapitalisations obligatoires, dont les paramètres sont choisis pour inciter les actionnaires à rémunérer leurs managers de la manière à les détourner des stratégies au risque de pertes extrêmes.Le 2ème essai développe le design de la supervision bancaire qui vise à éliminer le problème d'aléa moral au sein d'une banque, tout en assurant un coût minimum de supervisions. Les banques, dont la situation financière commence à se dégrader, doivent être soumises à des audits aléatoires. Les banques, dont la valeur de l'actif s'est dégradée considérablement, doivent être mises sous tutelle pour un redressement financier. Les auditeurs externes peuvent être impliqués dans le processus de supervision, mais ne doivent pas complètement remplacer les régulateurs. Le 3ème essai étudie comment la capacité d'emprunt de l'entreprise non-financière affecte sa politique d'investissement en présence des coûts d'émission de la dette. Il est montré que les entreprises, dont la capacité d'emprunt est moyenne, ont intérêt à réaliser un investissement plus important par rapport aux entreprises dont la capacité d'emprunt est relativement faible/forte. Cela est entièrement dû à l'effet des coûts fixes d'émission de la dette, qui émerge dans le contexte dynamique d'investissement. / This dissertation consists of 3 self-contained theoretical essays.Essay 1 brings into focus the problem of "manufacturing" tail risk in the banking sector. This work shows that, in order to prevent banks from engaging in tail risk, bank capital regulation should account for the internal agency problem between bank shareholders and bank top managers. It is proposed to design bank capital requirements in the form of incentive-based recapitalization mechanism which would induce bank shareholders to shape executive compensation in such a way as to prevent top managers from engaging in tail-risk.Essay 2 deals with the problem of moral hazard in bank asset management. It proposes the concept of incentive-based bank supervision aimed at preventing moral hazard at a minimum cost to the regulator. It is shown that the intensity of supervision efforts should be gradually adjusted to the bank's financial health: banks in the mild form of distress should be subject to random audits, whereas deeply distressed banks should be placed under temporary regulatory control. To prevent double moral hazard, external auditors involved in supervision should be offered the optimal incentive contract.Essay 3 examines the impact of credit rationing (debt capacity) on corporate investment in the setting with costly debt financing. It is shown that, when credit constraints are binding, the firms with intermediate levels of debt capacity will establish larger investment projects than the firms with relatively low or high debt capacity. This non-monotonicity of investment on debt capacity arises due to the effect of the lump-sum debt issuance costs in the dynamic context of investment.

Die vorliegende Dissertation besteht aus drei Kapiteln über die Investmentfonds. Das erste Kapitel befasst sich mit der Rolle der Fondsmanager in der Bilanzverschönerung. Auf Basis der Analyse der Karrierewege von amerikanischen Fondsmanagern werden signifikante zusammenwirkende Manager-Fixed-Effects identifiziert, die nach der Kontrolle der endogenen Matching-Probleme immer noch robust sind. Die geschätzten Manager-Fixed-Effects haben signifikante Einflüsse auf die Out-of-Sample-Vorhersagen. Außerdem wird festgestellt, dass die Verriegelungen der Investmentfonds, die von gemeinsamen Managern verwaltet wurden, wichtige Kanäle für die Bilanzverschönerung verursachen. Das zweite Kapitel beschäftigt sich mit den Investmentstrategien der Fonds im Hinblick auf die Nutzung von Credit Default Swaps (CDS). Die Zuordnung der CDS-Positionen der Investmentfonds zu ihrem Bestandportfolio bietet eine neue Methodik zur Identifizierung der CDS-Strategien und kompensiert somit die Analysen der existierenden Literatur auf der Makroebene. Die Ergebnisse zeigen, dass die Anreize zur Risikoreduzierung die Spekulationsanreize dominieren, insbesondere, wenn die Kreditexposition durch ungedeckte Leerverkäufe der CDS-Verträge erhöht wird. Die erfahrenen Fondsmanager tendieren dazu, mehr Kreditrisiko in Kauf zu nehmen, während es für die Fondsmanagerinnen wahrscheinlicher als für ihre männlichen Kollegen ist, gegen das bestehende Risiko abzusichern. Der letzte Teil nimmt die Pleite von Lehman Brothers unter die Lupe, um sich mit der daraus resultierenden unerwarteten Schließung der CDS-Positionen als einem natürlichen Experiment auseinanderzusetzten. Diese Studie dient zur Untersuchung der Risiko- und Leistungsimplikationen der CDS-Investments der Fonds. Die Investmentfonds besitzen bei ihren CDS-Transaktionen im Durchschnitt einen beachtlichen Teil Extremrisiko. Während die CDS-Nutzer von guten Gesamtmarktlagen profitieren, erleiden sie unter Verlusten bei geclusterten Ausfällen. / This dissertation comprises of three chapters on mutual funds. The first chapter establishes the role of managers in the deceptive practice of window dressing. Employing comprehensive career history of U.S. mutual fund managers, I find strong jointly significant manager fixed effects, which are robust after addressing endogenous matching concerns. The estimated manager fixed effects are significant in making out-of-sample predictions. Further I establish that mutual fund interlocks through common managers are important channels that spread window dressing. The second chapter studies the investment strategies of mutual funds regarding their use of credit default swaps (CDS). Matches between mutual funds’ CDS positions and their underlying portfolio in the holdings facilitate a new approach in identifying CDS strategies that complements the “macro” level analyses in the existing literature. I find risk reducing incentives are dominated by speculative incentives, especially those to increase credit exposure via naked short CDS contracts. Experienced fund managers tend to take on more credit risk, while female managers are more likely to hedge comparing with their male peers. The third chapter employs the collapse of Lehman Brothers and the resulting sudden closures of CDS positions as a natural experiment to examine the risk and performance implications of mutual funds’ CDS investments. Funds on average load up on a significant amount of tail risk by trading CDS. While CDS users benefit when market conditions are favorable, they suffer during periods of clustered defaults.

Le virus de l'immunodéficience humaine (VIH) est responsable du syndrome d'immunodéficience humaine acquise (SIDA). Le virus est très variable et est classé en divers sous-types dont le sous-type B qui est le plus étudié et le C qui est le plus répandu. L'enveloppe (Env) à la surface du virus lui permet d'infecter des cellules du système immunitaire, parmi lesquelles les lymphocytes T CD4 (LT CD4) et les macrophages sont des cibles privilégiées. Nous avons étudié le rôle de variations de séquences dans la partie de Env qui n'est pas exposée à la surface du virus (la queue intravirale (gp41CT)). Nos résultats montrent que ce domaine contribue à la réplication du virus dans les LT CD4 et que des variations dans ce domaine entravent l'assemblage des protéines de structure du virus, diminuant la production de nouveaux virus. Ce défaut n'est pas observé dans les macrophages, suggérant qu'un facteur cellulaire est impliqué. Identifier ce facteur pourrait fournir de nouvelles cibles antivirales / The human immunodeficiency virus (HIV) is responsible for the pandemic of acquired immunodeficiency syndrome (AIDS). Being highly variable, the virus has been subdivided into viral subtypes. Subtype B is the most studied, while subtype C is the most spread. The envelope (Env) expressed at the surface of the virion enables infection of cells involved in the immune system, like CD4 cells (CD4 TL) and macrophages. We studied the Env region not exposed at the viral surface (intraviral tail, gp41CT), which also harbors sequence characteristics linked to viral subtype. Viruses with subtype C gp41CT had lower replication capacities in CD4 TL. Microscopy analysis showed a defect in clustering of the viral structural protein Gag, revealing that changes in gp41CT affect assembly of all viral components. This defect was seen in CD4 TL but not in macrophages, suggesting the involvement of a cellular factor. Identifying this factor could open new therapeutic leads

Bases: A antinocicepção induzida por substâncias doces tem sido largamente estudada. Contudo, a investigação dos neurotransmissores envolvidos nesse processo antinociceptivo ainda carece de mais estudos, pois é de extrema importância entender o envolvimento desses neurotransmissores no sistema neural que controla este tipo de antinocicepção. Objetivo: O objetivo deste estudo é clarificar o envolvimento dos sistemas opióide e serotoninérgico na antinocicepção induzida por substância doce. Método: O presente trabalho foi realizado em modelo animal (Rattus norvegicus, Rodentia, Muridae), objetivando investigar se a ingestão crônica de solução de sacarose é seguida de antinocicepção. A latência de retirada de cauda após a aplicação de estímulo nocivo térmico foi medida antes e após esse tratamento no teste de retirada de cauda (provavelmente um reflexo espinal). Não houve diferenças estatisticamente significantes entre os valores de linha basal dos diferentes grupos e foi calculado um índice de analgesia da latência de retirada de cauda antes e depois do tratamento. O envolvimento de opióides endógenos e de serotonina neste processo antinociceptivo foi pesquisado com fármacos antagonistas específicos e não-específicos dos receptores opióides e serotoninérgicos. Resultados: O efeito analgésico da ingestão de sacarose depende da concentração da solução de sacarose e do tempo de duração do consumo da mesma. Naltrexona e metisergida diminuíram a antinocicepção induzida por substâncias doce (após 14 dias de ingestão da sacarose). Estes efeitos foram corroborados pela administração periférica de naloxonazina e cetanserina. Conclusões: Os resultados sugerem o envolvimento de opióides endógenos e serotonina no processo antinociceptivo atualmente estudado. Tudo apontando para a participação de receptores opióides µ1 e serotoninérgicos 5-HT2 na regulação central da antinocicepção induzida por substâncias doces. / Rationale: Sweet substance-induced antinociception has been widely studied, and the investigation of the neurotransmitters involved in the antinociceptive process is an important way for understanding the involvement of neural system controlling this kind of antinociception. Objective: The aim of this study is to investigate the involvement of opioid and serotonergic system in the sweet substance-induces antinociception. Methods: the present work was made in animal model (Rattus norvegicus, Rodentia, Muridae); with the aim of investigating if the chronic intake of sweet substance, such as sucrose, is followed by antinociception. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex) were measured before and immediately after this treatment. As there was not statistic significant differences between baseline values of different groups, an analgesia index was calculated from the withdrawal latencies before and after treatment. The involvement of endogenous opioid and serotonin in the antinociceptive process was investigated with specific and non-specific pharmacological antagonism on opioid and serotonergic receptors. Results: The analgesic effect of sucrose intake depends on the concentration of sucrose solution and on the time during which the solution is consumed. Naltrexone and methysergide decreased the sweet substance-induced antinociception (post 14 days of sucrose intake). These effects were corroborated by peripheral administration of naloxonazina and ketanserin. Conclusions: The present results suggest the involvement of endogenous opioids and serotonin in the antinociceptive process presently studied. µ1-opioid and 5-HT2 serotonergic receptors may be involved in the central regulation of the sweet substance-produced antinociception.

No description available.

由於許多資產報酬率的分配呈現厚尾的現象，因此，本文探討將最低報酬要求限制條件加入傳統的平均數╱變異數模型中，考慮在分配已知的情形下，假設資產報酬率的分配為t分配及常態分配，來求取最適的資產配置；在分配未知的情形下，利用古典Bootstrap法、移動區塊Bootstrap法及定態Bootstrap法的抽樣方法來模擬資產報酬率的分配形式，並利用模擬的資產報酬率分配求出最適的資產配置。 同時，本文亦探討資產配置在風險管理上的運用，當分配已知時，若對分配參數的估計正確，則使用的最低要求報酬率就是此資產配置的涉險值，反之，若對參數的估計錯誤時，會對資產配置產生很大的影響及風險管理上的不正確；當分配未知時，利用模擬方法來產生分配，則使用的最低要求報酬率可看成是此資產配置的涉險值。 實證部分選取資料分成本國及全球，研究發現對於何種分配或模擬方法的資產配置績效最好？沒有一定的結論。其原因是各種分配或模擬方法皆必須視資料的性質而定，因此，本論文的貢獻僅在建議使用厚尾分配及利用模擬方法，來符合資產報酬率呈現厚尾的現象，並利用此分配，以期在考慮最低報酬要求限制條件下的資產配置更為精確。 / The distributions of many asset returns tend to be fat-tail. This paper attempts to add the shortfall constraint in Mean-Variance Analysis. When the distribution is known, we find the optimal asset allocation under student-t distribution and normal distribution. On the other hand, we use Classical Bootstrap, Moving Block Bootstrap, and Stationary Bootstrap to stimulate the distribution of asset return, and to obtain the optimal asset allocation. We also examine the risk management of asset allocation. When we use the correct estimators of parameters under the known distribution, the threshold in shortfall constraint is the value-at-risk in asset allocation. Otherwise, if using the wrong estimators, we get the incorrect asset allocation and the improper risk management. When the distribution is unknown, using simulation to generate the distribution, the value-at-risk is the threshold. The empirical study is conducted in two parts, domestic and global asset allocation. The results cannot point out which distributions and simulations are suitable. They depend on the data’s property. The contribution of this paper is to introduce some methods to fit the fat-tail behavior of asset return in asset allocation.

<p>Drawing from the theoretical foundations of the “critical theory” of the Frankfurt School and the media ethnographic “cultural studies” approach of the british Birmingham School, this study attempts to sketch out a media theoretical overview of the contemporary state of media culture. Using the term convergence culture as the foundation, this study offers a theoretical background to the two contemporary streams that are the significant and distinct tendencies of convergence culture: intermedial convergence, its contemporary state and historical tendencies that can be traced back using the past media theoretical approach of the Frankfurt School, and cultural convergence, its contemporary state and historical tendencies, which lineage in a media theoretical context can be traced back to the british ethographic “cultural studies” field. Using contemporary drama serials to identify and pinpoint these two stream, this study shows how intermedial convergence expresses itself today through media conglomeration in terms of branding, product placement and marketing as the result of the “completed” convergence between screen culture and popular music as the current defining state of commodity culture. Using the contemporary british drama serial Doctor Who I examine the processes of meaning making among members of the television series fan culture on the popular video content page youtube.com as expressions of cultural convergence.</p><p>This study argues how the skills and talents developed in the interaction with popular culture and in a process of interaction between fans and participants (collective intelligence and participatory culture), will have an impact on the institutionalized knowledge “from above” and in a collective process will seep over to other fields of expertise. The study also argues, as a consequence of convergence culture, that in the contemporary state of online practices, social networking and in our interactions with digital media content, a mandatory “presence” has been created where we today are defined more through our online selves and these practices, than the ones that used to define us in our “physical” lives: “The medium is no longer just the message, we are living in a state where there is only messages”.</p>

Drawing from the theoretical foundations of the “critical theory” of the Frankfurt School and the media ethnographic “cultural studies” approach of the british Birmingham School, this study attempts to sketch out a media theoretical overview of the contemporary state of media culture. Using the term convergence culture as the foundation, this study offers a theoretical background to the two contemporary streams that are the significant and distinct tendencies of convergence culture: intermedial convergence, its contemporary state and historical tendencies that can be traced back using the past media theoretical approach of the Frankfurt School, and cultural convergence, its contemporary state and historical tendencies, which lineage in a media theoretical context can be traced back to the british ethographic “cultural studies” field. Using contemporary drama serials to identify and pinpoint these two stream, this study shows how intermedial convergence expresses itself today through media conglomeration in terms of branding, product placement and marketing as the result of the “completed” convergence between screen culture and popular music as the current defining state of commodity culture. Using the contemporary british drama serial Doctor Who I examine the processes of meaning making among members of the television series fan culture on the popular video content page youtube.com as expressions of cultural convergence. This study argues how the skills and talents developed in the interaction with popular culture and in a process of interaction between fans and participants (collective intelligence and participatory culture), will have an impact on the institutionalized knowledge “from above” and in a collective process will seep over to other fields of expertise. The study also argues, as a consequence of convergence culture, that in the contemporary state of online practices, social networking and in our interactions with digital media content, a mandatory “presence” has been created where we today are defined more through our online selves and these practices, than the ones that used to define us in our “physical” lives: “The medium is no longer just the message, we are living in a state where there is only messages”.

SUR2A-mediated regulation of KATP channels is affected by residues belonging to the C terminus of the first nucleotide binding domain (NBD1). We studied the C-terminal region of NBD1 by comparing experiments using NBD1 S615-D914 and NBD1 S615-K972 constructs to studies of NBD1 S615-L933 also performed in our laboratory. Our NMR data suggests that the C-terminal region of NBD1 from residues Q915 to L933 is disordered and transiently contacts the NBD1 core, which may affect NBD1 phosphorylation. Tryptophan quenching fluorescence experiments corroborate that the Q915-L933 C-terminal tail contacts the NBD1 core. Fluorescence thermal denaturation experiments suggest that NBD1 S615-D914 has a higher affinity for MgATP compared with NBD1 S615-L933, implying that the C-terminal tail varies MgATP binding. Additional experiments were performed to identify soluble constructs of hSUR1 NBD1 and rSUR2A NBD2 that would allow detailed biophysical studies of these domains. Some of the constructs studied showed improved solubility and stability.