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This novel is a family saga that follows Gülsün and her two daughters Sevda and Eda-Eva, who are half-sisters. Gülsün agrees to an arranged marriage with Haydar, a factory worker in Germany, and immigrates from her small village in Turkey to Germany. From this marriage Sevda is born. When she is old enough for kindergarten, Gülsün attends a German language course. She falls in love with the German instructor, Günther, and they begin an affair. Gülsün finds out that she is pregnant and abandons Sevda to live with Günther, who moves them to the outskirts of the city where Haydar cannot find her. Haydar, feeling emasculated and unable to take care of five-year-old Sevda, sends her to his family in Turkey for a couple of years. In a moment of intoxication, Gülsün sets out to reclaim Sevda and to unite her with her half-sister Eda-Eva, who knows nothing about Sevda’s existence. Gülsün, having chosen to follow the riverbank to reach the old apartment where she once lived, falls into the river and drowns. To connect Eda-Eva to her mother’s roots, Günther moves them to the city close to the Turkish community, where she makes friends with Sinem and realizes that she is queer. Years later on a train, Sevda and Eda-Eva meet and become friends, unaware of their connection. As their friendship deepens, the two fall in love. Both girls are desperate to leave their homes (Günther has built a new family for himself, in which Eda-Eva feels like a third wheel. Haydar has remarried a woman from his village back home, who takes out her sadness of infertility on Sevda). Eda-Eva suggests they move to the house in the outskirts, where she used to live with her mother. They arrive at the house that holds Gülsün’s memories in the basement. Lying in bed, the two create a fantasy of a future life together, although the truth becomes more and more undeniable to Sevda.

La régulation de l’expression des gènes joue un rôle fondamental dans la réponse et l’adaptation des cellules à leur environnement. L'expression des gènes peut être régulée à plusieurs étapes distinctes, mais un niveau de contrôle critique est l’initiation de la transcription. Celle-ci implique le recrutement séquentiel de nombreux régulateurs différents, dont les complexes co-activateurs. De nombreuses études ont démontré et caractérisé leurs fonctions dans la transcription. Cependant, il est moins bien compris comment les co-activateurs sont directement régulés par les conditions environnementales. Des travaux précédents de mon laboratoire de thèse ont montré, dans la levure fissipare Schizosaccharomyces pombe, que le complexe co-activateur SAGA contrôle l’expression des gènes en réponse aux nutriments et contribue ainsi à l’équilibre entre la prolifération cellulaire et la différenciation sexuelle. L’objectif de mon travail de thèse a été de comprendre comment le complexe SAGA répond à la disponibilité en nutriments et régule l’expression des gènes de différenciation. Pour cela, j’ai combiné des approches de génétique, de biochimie et de protéomique quantitative. Des analyses d’interactions génétiques m’ont permis de montrer que SAGA, par l’intermédiaire de sa sous-unité acétyltransférase Gcn5, contrôle l’équilibre entre prolifération et différenciation en aval des voies de signalisation TORC1 et TORC2. Puis, des études biochimiques ont établi que les voies de signalisation TORC1 et TORC2 contrôlent SAGA via la phosphorylation différentielle d’une sous-unité architecturale du complexe, nommée Taf12. En effet, lorsque les nutriments sont présents, TORC1 active la phosphatase PP2A, via la kinase Greatwall, pour déphosphoryler Taf12. Au contraire, la carence en nutriments active la voie de signalisation TORC2-AKT, qui permet la phosphorylation de Taf12, afin de moduler l’intensité de la réponse de différenciation. Nous avons également identifié d’autres sous-unités de SAGA qui sont différentiellement phosphorylées en fonction du niveau en nutriments et qui pourraient donc également contribuer à la régulation de SAGA. Notamment, nous avons observé que les sous-unités Ada3 et Sgf29, impliquées dans la régulation de l’activité de Gcn5, sont également phosphorylées dans les conditions carencées en nutriments. Enfin, j’ai observé que TORC2 et Gcn5 contrôlent la transition G2/M de façon synergique, suggérant que SAGA et les voies de signalisation des kinases TOR interagissent fonctionnellement dans le contrôle d’autres processus. Mon travail révèle que SAGA est une cible directe des voies de signalisation qui détectent les nutriments et établit un nouveau mécanisme par lequel TORC1 et TORC2 convergent pour contrôler l’expression génique et le destin cellulaire / The regulation of gene expression plays a fundamental role in the ability of cells to respond to external changes. One critical level of regulation is transcription, which is controlled by large complexes with many distinct activities. Little is known about how these activities integrate developmental or environmental signals to regulate transcription. We are using S. pombe as a model system to address this issue, in the context of cell fate control by nutrient availability. Previous work in the lab has established that, in this yeast, the SAGA co-activator complex controls whether cells proliferate or not in response to nutrients. Following up on these observations, we determined which nutrient-sensing signaling pathways regulate SAGA activities. A comprehensive genetic approach demonstrated that SAGA functions downstream of the TOR kinase-containing complexes, TORC1 and TORC2. In parallel, quantitative mass spectrometry analysis of the SAGA complex revealed that the Taf12 subunit is differentially phosphorylated, depending on nutrient levels. In agreement with our genetic analyses, Taf12 phosphorylation depends on the PP2A phosphatase, which we found is activated by TORC1 when nutrients are present. Conversely, upon nutrient starvation, TORC2 is activated allowing the AKT kinase to phosphorylate Taf12. We are now testing the in vivo roles of these modifications as well as their impact on SAGA functions at nutrient-regulated promoters. Altogether, our results contribute to a better understanding of the control of transcription by signal transduction pathways.

A studie about a male ideal in Sara Lidman''s novels Tjärdalen and Hjortronlandet, based on saga literature from Iceland.

Afin d’initier la transcription par l’ARN Polymérase II, la chromatine est modifiée par des coactivateurs, dont certains catalysent des modifications post-traductionnelles des queues des histones. La protéine GCN5 est une enzyme qui possède une activité histone acétyltransférase (HAT). Elle fait partie du complexe coactivateur SAGA, qui acétyle les histones H3. Or, il existe un second complexe HAT contenant GCN5 : le complexe ATAC, mis en évidence chez la drosophile. Chez l’homme en revanche, l’existence d’un tel complexe n’avait pas encore été démontrée au début de ma thèse.L’objectif de ma thèse a consisté tout d’abord en la purification et la caractérisation du complexe HAT ATAC chez l’homme. Puis, j’ai cherché à comprendre le fonctionnement et la spécificité d’action du complexe ATAC, par rapport au complexe SAGA.Dans une première partie, j’ai ainsi pu montrer que GCN5 fait partie d’un second complexe chez l’homme, le complexe ATAC. La composition en sous-unités du complexe ATAC a été déterminée et l’activité de ce dernier sur les histones étudiée. Nous avons pu démontrer que, comme hSAGA, hATAC acétyle les histones in vitro et in vivo, et préférentiellement la lysine 14 de l’histone H3. Chez les vertébrés, un paralogue de GCN5, PCAF peut se substituer à GCN5 dans les complexes ATAC ou SAGA.Par la suite, j’ai poursuivi la caractérisation de ces complexes HAT afin de comprendre le rôle des enzymes au sein des complexes et leurs fonctions. Pour cela, j’ai voulu comprendre le rôle des sous-unités, comment elles influencent l’activité de l’enzyme, et ainsi identifier les protéines qui permettent la spécificité de hATAC par rapport à hSAGA. / In order to initiate the transcription by the RNA polymerase II, chromatin needs to be modified by coactivators. Some of these coactivators are histone post-translational modifying complexes. GCN5 is a histone acetyltransferase enzyme (HAT), which can acetylate the histones. This enzyme is found in a multiproteic complex named SAGA. Recently, a second HAT complex containing GCN5 was discovered: ATAC, in drosophila. At the beginning of my thesis, the existence of such complex in human was not shown.My thesis objectives were then to identify and characterize an ATAC complex in human cells. In a first part, we purified and identified the composition in subunits of human ATAC. Then we studied the activity and specificity of ATAC on histone substrates, compared to SAGA. Next, we were wondering how the subunits of the two HAT complexes could play a role on the regulation of the activity of the enzyme GCN5, in order to understand the histone specificity of ATAC and SAGA.

Made available in DSpace on 2016-08-03T12:18:55Z (GMT). No. of bitstreams: 1 Adilson de Souza Filho.pdf: 1355236 bytes, checksum: 485c182c6fff3414c9acd232d7f61fc8 (MD5) Previous issue date: 2012-01-30 / What characterizes academic research in a doctoral course is that it should fulfill two fundamental requirements. The first is the element of innovation, the ability to enrich research on the theme. The second is that it should promote new ways of reading. We therefore believe that this thesis has met the expectation, the innovative element of this research being the deconstruction of the concept of the creation saga proposed by Karl Barth. It is new because we could not find, as we had suspected, any author, or even work or research that proposed to face the same task. Instead, there are even some authors that highly praise the research conducted by Karl Barth, as is the case of Coats and Brueggemann. Although they respond to some points of Barth s theology, they did not specifically deal with the concept of saga. The second aspect, structurally related to the first, is that it promotes new possibilities of reading. Using the approach of Paul Ricoeur, we propose a new biblical hermeneutics, based on what this author calls a long way, which makes use of various methods, including the historical-critical, to seek an interpretation of the text world which manages to make sense of the world outside the text. We believe that this proposal can overcome the purely dogmatic reading of the text world. According to Ricoeur, we believe that the foundational elements that guided the hermeneutic of Dasein, or even around the subject/object relation can contribute to a new hermeneutic, since it does not make the same concessions to the knowing subject. Thus, the possibility of a new reading appears from what Ricoeur has defined in dialectical relationship between the text world and the world outside the text, as a transforming and revelant representation. And this is where the Holy Scriptures has the the position of source of revelation and inspiration. / O que caracteriza uma pesquisa acadêmica num curso de doutorado é a apresentação de dois quesitos fundamentais. O primeiro é o elemento de inovação, capaz de enriquecer a pesquisa sobre o tema proposto. O segundo é o dos apontamentos como possibilidades de promoverem novos caminhos de releituras. Nesse sentido, nos convencemos de que a presente tese atende a expectativa, pois, o elemento inovador desta pesquisa é a desconstrução do conceito de saga da criação proposto por Karl Barth. É novo porque não encontramos, como suspeitávamos, nenhum autor, ou mesmo obra ou pesquisa que tenha proposto esta mesma tarefa. Ao contrário, há até alguns autores que enaltecem a pesquisa realizada por Karl Barth, como é o caso de Coats e Brueggemann. Apesar de reagirem a alguns pontos da teologia de Barth, porém, não o fizeram, especificamente, ao conceito de saga. O segundo quesito, estruturalmente ligado ao primeiro, é o que promove as possibilidades de releituras. A partir do pensamento de Paul Ricoeur propomos uma nova hermenêutica bíblica, fundamentada a partir daquilo que Ricoeur chamou de via longa, que utiliza-se de vários métodos, inclusive o histórico crítico, para se buscar uma interpretação do mundo do texto que gere sentido ao mundo frente ao texto. Acreditamos que esta proposta é capaz de superar a leitura puramente dogmática do mundo do texto. De acordo com Ricoeur, acreditamos que os elementos fundantes que pautaram a hermenêutica em torno do Dasein, ou mesmo, em torno da relação sujeito/objeto podem contribuir para uma nova hermenêutica, desde que não façam as mesmas concessões ao sujeito conhecente. Assim, a possibilidade de uma nova releitura se revela a partir daquilo que Ricoeur definiu, na relação dialética entre mundo do texto e mundo frente ao texto, como representância (réprésentance) revelante e transformante. E é nesse ponto que as Sagradas Escrituras ocupam o posto de fonte de revelação e inspiração.

A study has been made of (1) the various philosophies of idealism and materialism, (2) the effects of these philosophies upon the life and thought of England in the nineteenth and twentieth centuries, and (3) the demonstration of these philosophies in John Galsworthy's The Forsyte Saga with a view to indicating the trends and tendencies in the philosophy of England which have helped to shape the personal and national life of the British people of today.

Pour faciliter l’initiation de la transcription par l’ARN Polymérase II, le complexe co-activateur de la transcription SAGA possède une activité d’acétylation des histones H3 et une activité de déubiquitination des histones H2B, catalysée chez l’homme par l’enzyme USP22. Mon travail de thèse a porté sur l’étude de la régulation de cette activité de déubiquitination.Au sein de SAGA, USP22 interagit fortement avec trois protéines pour former un module structural appelé module de déubiquitination (DUBm). Nous avons montré que la formation d’un tel module était requise pour activer USP22. D’autre part, deux sous-unités du DUBm humain, ATXN7 et ATXN7L3, contiennent un domaine SCA7. Nos résultats montrent que le repliement structural adopté par ces deux doigts de zinc n’avait pas encore été décrit. Nous avons démontré que le domaine SCA7 de ATXN7 peut interagir avec un nucléosome in vitro et que cette interaction participe à la régulation fine de l’activité de déubiquitination de SAGA. Nous proposons qu’en interagissant avec le nucléosome, le domaine SCA7 de Sgf73 ou de ATXN7 pourrait positionner le DUBm de façon optimale par rapport à son substrat. / The SAGA complex is one of the most studied transcriptional co-activator complexes. To facilitate transcription by RNA Polymerase II, SAGA presents a modular organization and harbours two enzymatic activities. In human cells, these two enzymes are called GCN5 and USP22 and they can respectivelly acetylate histones H3 and deubiquitinate histones H2B. During my PhD thesis, I have worked on the regulation of SAGA deubiquitination activity. In the SAGA complex, USP22 interacts strongly with three other subunits to form a structural and functionnal module, named deubiquitination module (DUBm). We have shown that the free recombinant USP22 enzyme is not active, but that the formation of a stable DUBm triggers a strong stimulation of USP22 catalytic activity. Secondly, in human cells, two subunits of the DUBm, ATXN7 and ATXN7L3, contain a domain, called SCA7, that is not found in any other protein. Our results show that the new structural fold adopted by these two domains is specific to these zinc-fingers. These two SCA7 domains share a common structural heart, but their atomic structures reveal also differences, especially in the spatial organization of secondary structure elements. Indeed, we have shown that ATXN7 SCA7 domain can interact in vitro with a nucleosome which is not the case of ATXN7L3 SCA7 domain. Finally, I could show that in vivo the SCA7 domain of Sgf73, the ortholog of ATXN7 has a role in fine tunning SAGA deubiquitination activity. We hypothesize that the interaction between a nucleosome and the SCA7 domain of ATXN7 or Sgf73 would regulate SAGA deubiquitination activity by an optimal positionning of the module to its substrate.

This thesis aims to examine, through a comparative study with the original text, some of the translation choices made during the linguistic and cultural recoding process for the Italian readers of the Guta saga, one of the first historical and literary works of medieval Sweden, written in ancient Gutnic. The contrastive study of some passages of the original text of the Guta saga and of the Italian translation follows the method of critical analysis of literary translation developed by the French theorist Antoine Berman. This method aimed at finding the ‘deforming tendencies’ inherent in the act of translation, that threaten the translator's practice and influence in an unconscious way his linguistic and literary choices. The results of the thesis highlight on the one hand the presence in the Italian translation of the Guta saga of some of the ‘deforming tendencies’ outlined by Antoine Berman in his Analysis of translation, such as rationalization, clarification and expansion with the consequent destruction of rhythms, qualitative and quantitative impoverishment, ennoblement and the destruction of linguistic patterns, and on the other hand some ‘resistance strategies’ applied by the translator in order to delimit the ‘deforming tendencies’. This thesis also sheds light on some of the conscious and unconscious motivations, such as the original ambivalence of the translation project and the translator’s awe due to the aura of sacredness of this work, which underlie the ‘deforming tendencies’ and the ‘resistance strategies’ that have been observed. / Questa tesi si propone di esaminare, attraverso uno studio comparativo con il testo originale, alcune delle scelte traduttive operate durante il procedimento di ricodificazione linguistica e culturale per il pubblico italiano della Guta saga, una delle prime opere storiche e letterarie della Svezia medievale, redatta in gutnico antico. Lo studio contrastivo di alcuni passaggi del testo originale della Guta saga e della traduzione italiana segue il metodo di analisi critica della traduzione letteraria del teorico francese Antoine Berman, atto a reperire i sistemi di deformazione che minacciano la pratica del traduttore e operano in modo inconsapevole sul piano delle sue scelte linguistiche e letterarie. I risultati della tesi evidenziano, da un lato, la presenza di alcune delle tendenze deformanti delineate da Antoine Berman nella sua Analitica della traduzione, quali la razionalizzazione, la chiarificazione e l’allungamento con la conseguente distruzione dei ritmi, l’impoverimento qualitativo e quantitativo, la nobilitazione, la distruzione dei sistematismi, e, dall’altro, alcune strategie di resistenza applicate dal traduttore che limitano tali deformazioni. La presente tesi getta altresì luce su alcune delle motivazioni consce e inconsce, quali ad esempio l’ambivalenza originaria del progetto di traduzione e il sentimento di soggezione del traduttore di fronte all’aura di sacralità dell’opera tradotta, che stanno alla base delle tendenze deformanti e delle strategie di resistenza riscontrate.

Dagens applikationer är alltmer byggda enligt en mikrotjänstarkitektur istället för den klassiska monolitiska formen. I en mikrotjänstarkitektur har tjänster beroenden av varandra. Detta betyder att systemet måste kunna hantera situationer där dessa beroenden inte kan mötas. För att lösa de problemen som kan uppstå krävs ett felhanteringssystem som försäkrar att viktiga delar inte korrumperas eller går förlorad. Denna studie tar fram en modell på ett felhanteringssystem, och föreslår ett flertal teknologier som kan användas för en praktisk implementation av felhanteringssystemet. En fallstudie genomförs för att visa att teknologierna kan användas för att realisera modellen i en simulerad produktionsmiljö. Undersökningen föreslår en plattformsoberoende modell av Saga-mönstret som förhindrar korrumperad data, och ett återhämtningssystem som med hjälp av en meddelandekö kan återskapa förlorad data. Det framtagna felhanteringssystemet utvärderas utifrån de krav och begränsningar som ställs av beställaren, Asteria AB. Studien ger en generell lösning för de problem, som uppstår i en mikrotjänstarkitektur vid störningar och avbrott. Detta gör det möjligt att återanvända lösningen i olika kontext med minimala ändringar. / Today's applications are increasingly built according to a microservice architecture instead of the classic monolithic pattern. In a microservice architecture, services are interdependent. This means that the system must be able to handle situations where these dependencies cannot be met. To solve the problems that may arise, an error handling system is required that ensures that important parts are not corrupted or lost. This study develops a model of a fault management system, and proposes several technologies that can be used for a practical implementation of the fault management system. A case study is conducted to show that the technologies can be used to realize the model in a simulated production environment. The study proposes a platform-independent model of the Saga pattern that prevents corrupted data, and a recovery system that can recover lost data using a message queue. The developed error handling system is evaluated on the basis of the requirements and limitations set by the customer, Asteria AB. The study provides a general solution to the problems that arise in a microservice architecture in the event of disruptions and interruptions. This makes it possible to reuse the solution in different contexts with minimal changes.