Sterol regulatory element-binding proteins (SREBP) are transcription factors that regulate genes involved in lipid metabolism especially in the liver. Therefore, hepatic SREBP is significant regulator of systemic lipid metabolism. Evidence demonstrates that insulin and dietary unsaturated fatty acid (UFA) regulate SREBP1 expression and subsequent SREBP1-mediated gene transcription, events that in many instances result in modulation of systemic fatty acid and triglyceride (TG) homeostasis. A series of investigations was designed to uncover novel regulators of SREBP1. Dietary and exogenous addition of UFA has been shown to regulate SREBP function yet, an endogenous source of UFA capable of modulating SREBP remains elusive. Group VIA calcium-independent phospholipase A2 (iPLA2) releases UFA from the sn-2 position of glycerophospholipids. We hypothesized that iPLA2 provides UFA to suppress SREBP. iPLA2 overexpression and inhibition studies were implemented. iPLA2 inhibition increased SREBP1 expression, SREBP-mediated transcription and the expression of SREBP1 gene targets in vitro. In vivo overexpression of iPLA2 resulted in decreased expression of SREBP1 protein and plasma triglyceride. In contrast, iPLA2 overexpression attenuated SREBP1 expression, SREBP-mediated transcription and expression of SREBP1 targets genes. These data support the hypothesis that iPLA2 generates endogenous UFA that limit SREBP function. Use of a replication-deficient adenovirus 5 (Ad-5) expression vector in the iPLA2 study led to the unexpected observation of hepatic SREBP1 activation following Ad-5 infection. Because of this observation, we tested the hypothesis that replication-deficient Ad-5 might augment lipid synthesis in liver. We demonstrate that first generation Ad-5, a ubiquitous transgene expression vector, induces expression of SREBP1 and its target genes and leads to increases in fatty acid synthesis in vivo and in vitro. The phosphatidylinositol 3-kinase (PI3K) inhibitor, PX-866, suppressed Ad-5-induced SRBEP1 expression and hypertriglyceridemia implicating the PI3K/Akt pathway in Ad-5 activation of SREBP1. Use of PX-866 led to the discovery of a third mechanism of SREBP1 regulation. In vivo studies demonstrate that PX-866 modulates basal lipid metabolism in part through decreasing plasma TG, an increased trend toward decreased SREBP1 expression and a significant increase in plasma cholesterol. These studies characterize three distinct novel regulatory mechanisms of SREBP1.

by J. Kimemia, S.B. Gershwin. / Bibliography: leaf 6. / Caption title. / Supported by the National Science Foundation under Grant APR76-12036 National Science Foundation Grant DAR 78-17826

Leo VI (886-912) is an emperor who has suffered from a hostile and inadequate press. He has been portrayed as a weak and careless emperor, known mainly for his dubious parentage and marital exploits. This thesis questions these popular perceptions of Leo, and attempts to present a more realistic account of the emperor and the politics of his age. The aspects of the reign tackled focus on essential elements of Leo's life and rule, presented in a rough chronological framework, and the themes of personal relationships and political ideologies are recurrent. Chapter One examines Leo's relationship with Basil I and his attitude to his Macedonian heritage. Chapter Two considers the fate of the monumental figure of Photios at the emperor's hands. Chapter Three deals with the position and role of the 'all powerful' Stylianos Zaoutzes during the first half of the reign. Chapter Four ponders the origin and meaning of Leo's 'wise' epithet. Chapter Five focuses on the emperor's four marriages. Chapter Six turns to the course of foreign affairs during the reign, concentrating on Bulgaria and the Arab navy, and considers the emperor's attitude towards these military problems. Chapter Seven examines the emperor's relationship with his senatorial officials, focusing on two distinct groups, eunuchs and the generals who originated from families of the eastern frontier. Finally Chapter Eight addresses the tense relationship that existed between Leo and his brother and co-emperor Alexander. What emerges from a consideration of these aspects of Leo and his reign is that this is an emperor who does not deserve the popular perceptions that still persist about him. He was an emperor who forged a 'new' and distinctive imperial style, a style that should not deceive us; he may have been literate, sedentary and city-based, but he was also forceful, strong-willed and conscientious.

Le roman policier espagnol écrit au cours des trois dernières décennies se définit essentiellement comme un roman social urbain. Les déplacements des détectives mettent en lumière la cartographie d’un espace urbain espagnol en mutation, en accord avec les transformations subies par la société espagnole. Cette thèse se propose, à partir d’œuvres de quatre écrivains, Alicia Giménez Bartlett, Antonio Lozano, Juan Madrid et Andreu Martín, de dégager les lectures possibles de l’espace urbain qui permettent de mieux comprendre l’évolution de la société espagnole. Nous verrons d’abord un espace de proximité constitué d’une combinaison de lieux anthropologiques ; puis, un espace traversé de frontières visibles et invisibles qui entravent le mouvement d’une partie de la population ; enfin, un espace dans lequel la mobilité se généralise accentuant les inégalités entre ceux qui y ont accès et ceux qui sont condamnés à l’immobilité. Cette thèse propose une approche littéraire et sociologique du roman policier espagnol contemporain. / The Spanish crime novel that has been written over the last three decades can be essentially defined as an urban social novel. The movements of the detectives reveal the cartography of a Spanish urban space which is in mutation, reflecting the transformations undergone by Spanish society. Based on the work of four authors, Juan Madrid, Andreu Martín, Alicia Giménez Bartlett and Antonio Lozano, this thesis proposes various possible ways of interpreting that urban space, thus enabling a better understanding of the evolution of Spanish society. First of all, we encounter a space of proximity comprising a combination of places - as defined by Marc Augé ; then a space across which visible and invisible frontiers run, hindering mobility for a part of the population ; finally a space in which mobility is widespread, so emphasizing the inequality between those who have access to it and those who are condemned to staying put. This thesis thus proposes a literary and sociological approach to the contemporary Spanish crime novel.

O presente trabalho procura compreender o conceito de trauma psíquico a partir das teorizações de S. Freud e S. Ferenczi. Discutem-se as ideias expostas pelos dois autores sobre os aspectos intra e interpsíquicos envolvidos na formação do trauma, com o intuito de articulá-las de um modo que contemple as diferentes experiências de traumatização. A dissertação está dividida em três partes. Na primeira, composta de cinco capítulos, o eixo são experiências que parecem ter um efeito disruptivo tão logo acontecem, imediatamente ou após um curto intervalo de tempo. Incluem-se, aqui, as neuroses traumáticas, em geral, e as neuroses de guerra, em particular, assim como eventos de menor intensidade, mas que demandam um trabalho característico do aparelho psíquico. A atenção de Freud e Ferenczi voltou-se para esse tipo de formação traumática, em um tempo, após a Primeira Guerra Mundial, devido à necessidade de compreender e tratar soldados com sintomas que remetiam às experiências de trauma. Devido ao despreparo, à ausência de contrainvestimento do sistema consciente, e à intensidade da estimulação, o psiquismo é obrigado a acionar medidas defensivas primitivas, na tentativa de ligar o afluxo de excitação. Na segunda parte deste estudo, dividida em quatro capítulos, discutem-se as teorizações dos autores-base que explicitam a formação do trauma em dois tempos distintos. O modelo deriva do observado nas experiências de sedução. Para Freud, algumas vivências não são traumáticas no momento em que ocorrem, mas ganham esse atributo posteriormente, ao serem reativadas por uma nova experiência que as ressignifica. Para Ferenczi, algumas formas de traumatização envolvem o que chama de duplo choque: uma experiência causa comoção psíquica e, quando o indivíduo busca no ambiente a validação e o reconhecimento de suas sensações e percepções, estas são negadas. Utilizando casos clínicos colhidos da literatura sobre o tema, e cotejando a relação pessoal entre os autores, procura-se articular os modelos de traumatização observados. No capítulo final, conclusivo, acompanha-se a tentativa de Michael Balint de decompor a formação do trauma em três fases, unindo as ideias de Freud e Ferenczi, e propõe-se, com base no que foi discutido, a hipótese de que alguns tipos de formação traumática envolvem três tempos: o momento do choque, a reação do ambiente após o evento, e a ressignificação a posteriori das experiências anteriores / In this work I advance an understanding of the concept of psychic trauma based on Freuds and Ferenczis theoretical deliberations. I discuss both authors ideas concerning intra- and inter-psychic aspects of trauma formation so as to articulate them in such a way that I may distinguish different traumatic experiences. This work is divided into three parts. In the first five chapters I show that the focal point of a particular type of trauma is a set of experiences that appear to have an immediate or shortly delayed disruptive effect. In this set one finds traumatic neuroses in general and wartime neuroses in particular, as well as less intense events that nonetheless require a characteristic effort on the part of the psychic apparatus. Owing to the need to understand and treat soldiers whose symptoms derived from their traumatic experiences, both Freud and Ferenczi directed their attention to this type of trauma formation after the World War I. Because of psychic unpreparedness, the conscious systems lack of counter-cathexis, and the stimulations intensity, the psyche is forced into activating primitive defenses in its attempts to bind the overwhelming excitation. In the second part (four chapters), I discuss these foundational authors theoretical deliberations concerning the formation of trauma in two different stages. The model here derives from what has been observed in experiences of seduction. For Freud some experiences are not traumatic when they occur, but they become traumatic later, when they are reactivated by another experience that redefines them. For Ferenczi, some forms of traumatization entail what he calls a double shock: an experience causes psychic commotion, and, when subjects search their environment for validation and for acknowledgement of their sensations and perceptions, these are denied. Using pertinent clinical cases found in the literature and availing myself of Freuds and Ferenczis personal relationship, I attempt to delineate these two models of traumatization. In my concluding chapter I examine Michael Balints attempt to break down trauma formation into three phases by uniting Freuds and Ferenczis points of view. I propose, based on what has come before, the hypothesis that some types of trauma formation entail three phases: the moment of shock, the environments reaction after the event, and the a posteriori reinterpretation of the prior experiences