No description available.

La recombinaison méiotique n'est pas distribué de manière aléatoire le long des chromosomes, mais est caractérisée par des domaines froids et chauds qui limitent la diversité génétique transmise par les gamètes. Cependant, le profil de la recombinaison méiotique peut être modifiée, étant donné que la fusion de l’ endonucléase Spo11 au domaine de liaison à l'ADN de Gal4 est suffisante pour favoriser la formation des cassures double brin (CDB) et la recombinaison à proximité des sites de liaison de Gal4, dans la levure et dans les souris. Ici, dans la levure Saccharomyces cerevisiae, nous avons étudié l'effet de la fusion de Spo11 à 8 protéines de liaison à l'ADN lors de la méiose. Comme modules de ciblage, nous avons utilisé des facteurs de transcription de levure et des protéines artificiels de liaison à l'ADN (TALEs et ZFs), qui sont apparus comme des outils efficaces pour faire varier la position et / ou le nombre de sites ciblés. Lors de l'expression de chacun des fusions Spo11, nous avons examiné la progression de la méiose, la formation des CDB dans les sites naturels et ciblées ainsi que le niveau relatif de la recombinaison méiotique. Ce travail dans l’organisme modèle levure ouvre de nouvelles voies pour modifier la recombinaison méiotique chez d'autres organismes, tels que des mammifères et des plantes, pour augmenter la diversité génétique dans les sites d'intérêt et disséquer l'information génétique, en surmontant les limitations dues à la liaison génétique. / Meiotic recombination is not randomly distributed along the chromosomes, but is characterized by hot and cold domains that limit the genetic diversity transmitted by the gametes. However, the recombination profile can be modified, since the tethering of Spo11 endonuclease, upon fusion to the Gal4 DNA-binding domain, is sufficient to enhance DSB formation and recombination near several Gal4 consensus binding sites, in yeast and in mouse. Here, in the yeast Saccharomyces cerevisiae, we studied the effect of Spo11 fusions to 8 different DNA-binding proteins during meiosis. As targeting modules, we used yeast full-length transcription factors and artificial DNA-binding modules (TALEs and ZFs), which emerged to be efficient tools to vary the location and /or the number of targeted sites. Upon expression of each of the Spo11 fusions, we examined meiotic progression, DSB formation at natural and targeted sites as well as the relative level of meiotic recombination. This work in the yeast model opens new avenues to modify meiotic recombination in other organisms, such as mammals and plants, to boost genetic diversity at sites of interest and to dissect the genetic information, overcoming the restrictions due to the genetic linkage.

The aim of the master thesis is to sum up theoretical information about beamforming methods of microphone arrays and to verify their functionality. At the beginning of this work there are simulated different varietes of linear uniform and nonuniform microphone arrays and circular arrays. The results are verificated by a practical measurement in ideal conditions. Then I will focuse on implementation of the DAS(Delay And Sum), SAB(Sub Array Beamforming), CDB(Constant Directivity Beamforming), CDB-CA(CDB-Circular Arrays) beamformer including theoretical and practical verification of the functionality in ideal conditions. At the end of this thesis are all beamforming methods compared with each other at SNR(signal to Noise Ratio) and directivity parameters.

Three dimensional visualisation achieves tremendous savings in time and costs during the design process. Due to these circumstances this methods are gaining in importance. For example improvement in performance and the product security or enabling the operative optimization of a production sequence. By the virtual testing it is possible to validate a product in the whole developing process and product lifecycle. The flight simulator ATILa at Airbus Defence and Space in Friedrichshafen uses these advantages for own products. ATILa is used to test intelligent assistance systems for helicopter pilots. Here the graphic implementation of the virtual earth plays a key role when practicing realistical scenarios. This approach is implemented with the Common Database (CDB) which is enabled by the definition of specifications and standards. Different commercial software packages by Presagis are used to implement the aforementioned database. The software Terra Vista is used for the database generation, including the compilation. For the CDB implementation the software Vega Prime is used to prepare the data with the help of the RTP. The software Vega Prime is not able to display 3D models with LODs, due to a software error. Therefore a third software named Creator is used to modify them. The 3D models are available in the OpenFlight Format. This OpenFlight format consists of different kind of nodes with a complex hierarchical structure. Other software solutions, such as Autodesk or Blender, are not able to provide access to the specific structure. The edited models can be integrated in the virtual environment and have to defined by unambiguous indices. Various settings are used to implement the objects automatically. The compilation of the area of interest takes place by the definition of a geotile with a specific size depending on the latitude. The CDB ouput will be transferred by Vega Prime and with the help of the RTP into the simulator. In addition, there is the possibility to render various CDB databases in the simulator to enable a visualisation of the complete earth. Finally, any errors occurring will be described and methods of resolution explained. The complexity of the generation process of a CDB database could be represented with this thesis. However, the whole workflow of the visualisation of the earth is still in its initial stages, since among other things there are errors in the software. To sum up; the potential of the CDB can be evaluated as above average. / Die 3D Visualisierung vereinfacht den Planungsprozess und geht somit mit einer Zeit- und Kosten- einsparung einher. Aufgrund dieser Sachverhalte gewinnt sie immer weiter an Bedeutung, um zum Beispiel eine verbesserte und sichere Benutzung eines Produktes oder einen optimierten Betrieb einer Produktionskette zu ermöglichen. Durch vorherige virtuelle Erprobung und Vali- dierung eines Produktes können Kosten für den gesamten Entwicklungsprozess und den Pro- duktlebenszyklus gering gehalten werden. Im Flugsimulator für Helikopter namens ATILa in Friedrichshafen (Airbus Defence and Space) versucht man die genannten Vorteile für die eigenen Produkte zu nutzen. Im ATILa werden Assistenzsysteme geprüft, welche die Helikopterpiloten während ihres Fluges unterstützen sollen. Hierbei spielt die grafische Umsetzung der virtuellen Erde in dem Simulator eine entscheidende Rolle, um die Szenarien realitätsnah durchführen zu können. Dies kann mit Hilfe einer sogenannten Common Database (CDB), die durch Spezi- fikationen und Standards definiert ist, umgesetzt werden. Mittels verschiedener kommerzieller Softwarepakete der Firma Presagis lässt sich die oben genannte Datenbank erstellen. Die Gener- ierung und Kompilierung wird mit dem Softwareprogramm Terra Vista vorgenommen. Die Imple- mentierung der CDB in den Flugsimulator erfolgt mit der Software Vega Prime, welche die Daten über einen RTP zur Verfügung stellt. Da dieses Programm durch einen Softwarefehler nicht in der Lage ist, 3D Modelle mit verschiedenen Detaillierungsgraden darzustellen, muss eine dritte Soft- ware namens Creator genutzt werden. Die 3D Modelle liegen im OpenFlight Format vor. Dieses OpenFlight Format weist eine komplexe hierarchische Struktur aus verschiedenen Knoten auf. Andere Softwarelösungen, wie Autodesk oder Blender, sind nicht in der Lage einen Einblick in die spezielle Struktur zu geben. Die bearbeiteten Modelle können dann in der virtuellen Umgebung eingebunden und müssen durch eindeutige Indizes definiert werden. Verschiedene Einstellun- gen werden genutzt, um Objekte automatisch einzubinden. Die Kompilierung des Interessenge- bietes erfolgt über die Definition einer Geokachel mit einer bestimmten Größe, die abhängig vom Breitengrad ist. Die ausgegebene CDB wird mit Vega Prime und mit Hilfe des RTPs in den Simu- lator übertragen. Des Weiteren gibt es die Möglichkeit verschiedene CDB Datenbanken im Sim- ulator simultan zu rendern, was eine vollständige Visualisierung der kompletten Erde ermöglicht. Abschließend werden aufgetretene Fehler näher beschrieben und Lösungsansätze erläutert. Mit der vorliegenden Arbeit konnte die Komplexität der Entstehung einer CDB Datenbank dargestellt werden. Dennoch befindet sich der gesamte Arbeitsablauf der Visualisierung der Erde noch am Anfang, da u.a. Softwarefehler zu bemängeln sind. Zusammenfassend kann das Potenzial einer CDB als überdurchschnittlich bewertet werden.

Made available in DSpace on 2014-08-20T13:25:43Z (GMT). No. of bitstreams: 1 Dissertacao_Roberto_ Carlos_Doring_ Wolter.pdf: 973904 bytes, checksum: 67cf8c20b65c6a70b13833df022a0d9c (MD5) Previous issue date: 2010-03-05 / Iron toxicity can cause considerable reductions in the productivity of rice, depending on the severity of symptoms and the affected area in the field. It is necessary to identify the factors that determine the occurrence of this nutritional disorder, so that effective measures may be carried out to correct this problem in the field. The objective of this study is to verify that the interpretation criteria for prognosis of the risk of iron toxicity in flooded rice using the soil analysis are reliable for a particular group of lowland soils. Thus, an experiment was conducted in the greenhouse, and the treatments made up of eleven lowland soils structured with a one-factor randomized block design, with four replications. The indicators were: iron extracted from the soil and the CEC, to estimate the percentage of saturation of CEC by Fe2+, percentage of symptoms of iron toxicity, weight of dry matter, and calcium, magnesium, iron and manganese contents in the soil solution and plant tissue. The results were subjected to analysis of variance (Duncan test) at 5% probability, and simple linear correlation of Pearson analyzes (whereas levels greater than 95%). The indicators which have the best efficiency to predict the risk of toxicity by iron is the iron concentrationt in the soil solution and PSFe2+. The PSFe2+ has a high correlation coefficient with the concentration of iron in the soil solution. No symptoms of toxicity by iron is observed when the mole ratio of iron by divalent cations in soil solution is less than 0.30. The extraction of iron by ammonium oxalate at pH 6.0 is a good indicator for estimating the iron that is accumulated during the flooding. The interpretation for prediction of the risk of occurrence of iron toxicity in rice proposed by SOSBAI (2007) based on PSFe2+ is efficient for predicting the occurrence of the problem for the group of soils in the study. / A toxidez de ferro pode causar reduções consideráveis na produtividade do arroz, dependendo da intensidade dos sintomas e da área afetada na lavoura. É necessário identificar os fatores que determinam a ocorrência dessa desordem nutricional, afim de que possam ser realizadas medidas efetivas para corrigir esse problema na lavoura. O objetivo do presente trabalho é verificar se os critérios de interpretação para prognóstico do risco de ocorrência da toxidez por ferro em arroz irrigado por alagamento a partir da análise de solo são válidos para um determinado grupo de solos de várzea. Para isso, foi conduzido um experimento em casa de vegetação, sendo os tratamentos compostos por onze solos de várzea estruturados num unifatorial com delineamento em blocos casualizados, com quatro repetições. Os indicadores avaliados foram: ferro extraído do solo e a CTC, para a estimação da porcentagem de saturação da CTC por Fe2+, porcentagem de sintomas de toxidez por ferro, peso de massa seca, e as concentrações de cálcio, magnésio, ferro e manganês na solução do solo e na parte aérea das plantas. Os resultados foram submetidos à análise de variância (teste de Ducan) a 5% de probabilidade, e realizadas análises de correlações lineares simples de Pearson (considerando níveis maiores que 95%). Os indicadores que apresentam a melhor eficiência para prever o risco de ocorrência de toxidez por ferro são a concentração de ferro na solução do solo e a PSFe2+. A PSFe2+ apresenta alto coeficiente de correlação com a concentração de ferro na solução do solo. Nenhum sintoma de toxidez por ferro é observado quando a fração molar de ferro pelos cátions divalentes na solução do solo é inferior a 0,30. A extração de ferro por oxalato de amônio a pH 6,0 é um bom indicador para se estimar o ferro que é acumulado durante o alagamento do solo. A interpretação para prognóstico do risco de ocorrência da toxidez por ferro em arroz irrigado proposto por SOSBAI (2007) baseada na PSFe2+ é eficiente para previsão da ocorrência do problema para o grupo de solos do estudo.

Three dimensional visualisation achieves tremendous savings in time and costs during the design process. Due to these circumstances this methods are gaining in importance. For example improvement in performance and the product security or enabling the operative optimization of a production sequence. By the virtual testing it is possible to validate a product in the whole developing process and product lifecycle. The flight simulator ATILa at Airbus Defence and Space in Friedrichshafen uses these advantages for own products. ATILa is used to test intelligent assistance systems for helicopter pilots. Here the graphic implementation of the virtual earth plays a key role when practicing realistical scenarios. This approach is implemented with the Common Database (CDB) which is enabled by the definition of specifications and standards. Different commercial software packages by Presagis are used to implement the aforementioned database. The software Terra Vista is used for the database generation, including the compilation. For the CDB implementation the software Vega Prime is used to prepare the data with the help of the RTP. The software Vega Prime is not able to display 3D models with LODs, due to a software error. Therefore a third software named Creator is used to modify them. The 3D models are available in the OpenFlight Format. This OpenFlight format consists of different kind of nodes with a complex hierarchical structure. Other software solutions, such as Autodesk or Blender, are not able to provide access to the specific structure. The edited models can be integrated in the virtual environment and have to defined by unambiguous indices. Various settings are used to implement the objects automatically. The compilation of the area of interest takes place by the definition of a geotile with a specific size depending on the latitude. The CDB ouput will be transferred by Vega Prime and with the help of the RTP into the simulator. In addition, there is the possibility to render various CDB databases in the simulator to enable a visualisation of the complete earth. Finally, any errors occurring will be described and methods of resolution explained. The complexity of the generation process of a CDB database could be represented with this thesis. However, the whole workflow of the visualisation of the earth is still in its initial stages, since among other things there are errors in the software. To sum up; the potential of the CDB can be evaluated as above average. / Die 3D Visualisierung vereinfacht den Planungsprozess und geht somit mit einer Zeit- und Kosten- einsparung einher. Aufgrund dieser Sachverhalte gewinnt sie immer weiter an Bedeutung, um zum Beispiel eine verbesserte und sichere Benutzung eines Produktes oder einen optimierten Betrieb einer Produktionskette zu ermöglichen. Durch vorherige virtuelle Erprobung und Vali- dierung eines Produktes können Kosten für den gesamten Entwicklungsprozess und den Pro- duktlebenszyklus gering gehalten werden. Im Flugsimulator für Helikopter namens ATILa in Friedrichshafen (Airbus Defence and Space) versucht man die genannten Vorteile für die eigenen Produkte zu nutzen. Im ATILa werden Assistenzsysteme geprüft, welche die Helikopterpiloten während ihres Fluges unterstützen sollen. Hierbei spielt die grafische Umsetzung der virtuellen Erde in dem Simulator eine entscheidende Rolle, um die Szenarien realitätsnah durchführen zu können. Dies kann mit Hilfe einer sogenannten Common Database (CDB), die durch Spezi- fikationen und Standards definiert ist, umgesetzt werden. Mittels verschiedener kommerzieller Softwarepakete der Firma Presagis lässt sich die oben genannte Datenbank erstellen. Die Gener- ierung und Kompilierung wird mit dem Softwareprogramm Terra Vista vorgenommen. Die Imple- mentierung der CDB in den Flugsimulator erfolgt mit der Software Vega Prime, welche die Daten über einen RTP zur Verfügung stellt. Da dieses Programm durch einen Softwarefehler nicht in der Lage ist, 3D Modelle mit verschiedenen Detaillierungsgraden darzustellen, muss eine dritte Soft- ware namens Creator genutzt werden. Die 3D Modelle liegen im OpenFlight Format vor. Dieses OpenFlight Format weist eine komplexe hierarchische Struktur aus verschiedenen Knoten auf. Andere Softwarelösungen, wie Autodesk oder Blender, sind nicht in der Lage einen Einblick in die spezielle Struktur zu geben. Die bearbeiteten Modelle können dann in der virtuellen Umgebung eingebunden und müssen durch eindeutige Indizes definiert werden. Verschiedene Einstellun- gen werden genutzt, um Objekte automatisch einzubinden. Die Kompilierung des Interessenge- bietes erfolgt über die Definition einer Geokachel mit einer bestimmten Größe, die abhängig vom Breitengrad ist. Die ausgegebene CDB wird mit Vega Prime und mit Hilfe des RTPs in den Simu- lator übertragen. Des Weiteren gibt es die Möglichkeit verschiedene CDB Datenbanken im Sim- ulator simultan zu rendern, was eine vollständige Visualisierung der kompletten Erde ermöglicht. Abschließend werden aufgetretene Fehler näher beschrieben und Lösungsansätze erläutert. Mit der vorliegenden Arbeit konnte die Komplexität der Entstehung einer CDB Datenbank dargestellt werden. Dennoch befindet sich der gesamte Arbeitsablauf der Visualisierung der Erde noch am Anfang, da u.a. Softwarefehler zu bemängeln sind. Zusammenfassend kann das Potenzial einer CDB als überdurchschnittlich bewertet werden.

The Latin America, the richest continent in the planet's biodiversity, has been subject to expropriation by multinational corporations seeking access to plants and animals or knowledge related to biodiversity, produced by indigenous peoples or traditional communities, which will give support to the scientific findings used by large industries in the production of medicines, cosmetics and a wide variety of products available in the market, for wich the industries claimed intellectual property rights, with the exclusion of traditional populations. In this scenario, there are overlaps between The CBD and TRIPs Agreement in multilateral settings, where the possibility of protecting biodiversity shares space with the same tendency to your merchandization. Although the The CBD and TRIPs Agreement structure different international issues, this norms interact from the granting of intellectual property rights on biodiversity products. Because of this, the research aims to comprehend the extent to which intellectual property rights under the WTO model, notably patents, impact on biodiversity protection by the Latin American countries. Investigates the multilateral regulation of biodiversity protection and intellectual property with the central analysis, respectively, in the CBD and TRIPs. Then, the structures of the multilateral system are confronted with a sui generis system, in order to find out if they are alternatives to protect biodiversity in Latin America. Thus, was possible to conclude that the Latin American countries have their possibilities to care of the biodiversity limited by international regime of intellectual property, which allows private ownership of biodiversity in the form of biotechnologies. This provides two contrary ways: to maintain the international regime of intellectual property that ensures the trade of bio-merchandise with patents, or to structure a regulatory framework to care of biodiversity, in the Conference of the Parties to the CBD and negotiations in the Council for TRIPs. However, the strong opposition of the North countries to the interests of Latin American countries leads to investigate a sui generis system, to articulate a unified position in Latin America for the international confrontation and have for basis the guarantee of rights to the traditional peoples on their traditional knowledge. / A América Latina, continente com maior riqueza em biodiversidade do planeta, tem sido submetida à expropriação por empresas multinacionais que buscam acesso a espécies de plantas e animais ou a saberes dos povos indígenas ou comunidades tradicionais sobre a biodiversidade, que darão suporte a descobertas científicas utilizadas por grandes indústrias na produção de medicamentos, produtos cosméticos e os mais variados bens disponíveis no mercado, para os quais são reivindicados direitos de propriedade intelectual, em exclusão das populações tradicionais. Nesse cenário, ocorrem as sobreposições entre a CDB e o TRIPs nas regulações multilaterais, a partir do que a possibilidade de proteção da biodiversidade compartilha espaço simultâneo com a tendência à sua mercantilização. Embora estruturem questões internacionais distintas, a CDB e o TRIPs interagem a partir da concessão de direitos de propriedade intelectual sobre produtos da biodiversidade. Em razão disso, a pesquisa buscou compreender em que medida os direitos de propriedade intelectual sob o modelo da OMC, notadamente as patentes, interferem na proteção da diversidade biológica pelos países da América Latina. Investiga-se a regulação multilateral de proteção da biodiversidade e de propriedade intelectual com a análise centralizada, respectivamente, na CDB e no TRIPs. Em seguida, são confrontadas as estruturas do sistema multilateral a um sistema sui generis, com o objetivo de descobrir se constituem alternativas de proteção da biodiversidade pela América Latina. Assim, foi possível concluir que os países latino-americanos têm suas possibilidades de cuidar da biodiversidade limitadas pelo regime internacional de propriedade intelectual, que permite a apropriação privada da biodiversidade em forma de biotecnologias. A partir disso surgem dois caminhos opostos: manter o regime internacional de propriedade intelectual que assegura o comércio de biomercadoria patenteada; ou estruturar um marco regulatório para o cuidado da biodiversidade, nas Conferências das Partes da CDB e em negociações no Conselho TRIPs. Porém, uma forte oposição dos países do Norte aos interesses dos países latino-americanos leva à investigar um sistema sui generis, que articule uma posição unificada da América Latina para o embate internacional e tenha por fundamento a garantia de direitos aos povos tradicionais sobre seus conhecimentos.

La surexpression de la lamine B1, un composant majeur de l'enveloppe nucléaire, a été rapportée dans diverses tumeurs. Cependant, les causes et les conséquences de cette augmentation sur la stabilité du génome n'ont pas été étudiées à ce jour. En effet, l'instabilité du génome est considérée comme une caractéristique majeure des cellules cancéreuses. Pour assurer le maintien de la stabilité du génome, les cellules ont développé de multiples et complexes mécanismes parmi lesquels les voies de réparation de l'ADN et la gestion du stress réplicatif sont essentielles. Au cours de ma thèse, l'impact de l'augmentation de niveau de lamine B1 sur la stabilité du génome, en particulier sur la réparation de cassure double-brin (CDB) et sur le contrôle du stress réplicatif a été étudié. En effet, nous montrons qu'une augmentation de la lamine B1 entraîne une accumulation de CDB et leur persistance en réponse à l'irradiation (foyers γH2AX), en plus d'une sensibilité accrue à l'irradiation (formation de colonies et cassures chromosomiques). Les cellules surexprimant la lamine B1 montrent également des défauts de recrutement de 53BP1 aux sites de dommages d’ADN, couplés à une diminution de l'efficacité de la réparation de CDB par NHEJ (Non-Homologous End-Joining). De plus, nous avons identifié une interaction directe entre la lamine B1 et 53BP1 régulant le recrutement de ce dernier aux CDB. Nos résultats supportent un modèle dans lequel l'augmentation de la lamine B1 conduit à la séquestration de 53BP1, modifiant ainsi son recrutement aux CDBs. En parallèle, nous montrons que les cellules surexprimant la lamine B1 présentent des signes accrus de stress réplicatif tels que l'accumulation de foyers spontanés de p-RPA, l'augmentation des figures radiales lors du traitement par mitomycine C, et une sensibilité accrue au traitement par camptothécine. Nous avons en outre cherché à identifier les causes de l'augmentation du stress réplicatif dans ces cellules, et les conséquences potentielles, en particulier sur l'induction de phénotypes inflammatoires. En fait, nous montrons que la surexpression de la lamine B1 conduit à une diminution de l'efficacité de la réparation de CDB par la recombinaison homologue, couplée à un défaut de formation de foyers BRCA1 après irradiation. De plus, nous avons obtenu des données préliminaires suggérant une induction de l'inflammation lors de la surexpression de la lamine B1. En résumé, ce travail de Thèse a permis d’identifier un nouveau mécanisme régulant le recrutement de 53BP1 aux CDB par son interaction avec la lamine B1, et souligne le rôle de l'augmentation de la lamine B1 dans la promotion de l'instabilité génomique au moins partiellement par des défauts de réparation de CDB et une augmentation de stress réplicatif. Après confirmation de l'induction de phénotypes inflammatoires, nous aurions identifié des rôles de l'augmentation de la lamine B1 dans la promotion de deux caractéristiques majeures du cancer - l'instabilité génomique et l'inflammation - favorisant ainsi le rôle de la lamine B1 dans le développement tumoral et proposant cette dernière comme une cible thérapeutique antitumorale potentielle. / The overexpression of lamin B1, a major component of nuclear envelope, has been reported in various tumors. However, the causes and consequences of this increase on the genome stability have not been studied to date. Indeed, genome instability is considered a major hallmark of cancer cells. To ensure the maintenance of genome stability, cells have developed multiple complex mechanisms among which pathways of DNA repair and replication stress management are essential. Therefore, during my thesis the impact of an increased lamin B1 level on genome stability, in particular on double-strand break (DSB) repair and on the control of replication stress was studied. Indeed, we show that increased lamin B1 leads to an accumulation of DSBs and their persistence in response to irradiation (γH2AX foci), in addition to an increased sensitivity to irradiation (colony formation and chromosomal breaks). Lamin B1 overexpressing cells also show defects in the recruitment of 53BP1 to damage sites, coupled to a decreased efficiency of DSB repair by Non-Homologous End-Joining. Moreover, we identified a direct interaction between lamin B1 and 53BP1 regulating the latter’s recruitment to DSBs. Our results support a model where increased lamin B1 leads to the sequestration of 53BP1, thereby altering its recruitment to DSBs. In parallel, we show that cells overexpressing lamin B1 display increased signs of replication stress such as accumulation of spontaneous p-RPA foci, increased radial chromosomes upon mitomycin C treatment, and enhanced sensitivity to treatment with camptothecin. We further aimed to identify the causes of the increased replication stress in these cells, in addition to the potential consequences, in particular on the induction of inflammatory phenotypes. In fact, we show that lamin B1 overexpression leads to a decreased efficiency of DSB repair by Homologous Recombination, coupled to a defect in irradiation-induced BRCA1 foci formation. In addition, we obtained preliminary data suggesting a possible induction of inflammation upon lamin B1 overexpression. Altogether, this work identifies a novel mechanism regulating the recruitment of 53BP1 to damage sites through its interaction with lamin B1, and highlights the role of increased lamin B1 in promoting genome instability at least partially through defective DSB repair and increased replication stress. Upon confirming the induction of inflammatory phenotypes, we would have identified roles of increased lamin B1 in promoting two major hallmarks of cancer – genomic instability and inflammation - thereby favorizing a role for lamin B1 in tumor development and proposing the latter as a potential anti-tumor therapeutic target.

Comprendre les modes d'interaction des rayonnements ionisants avec la matière vivante, notamment lors de l'exposition à de faibles doses telles que celles que l'on peut trouver dans un environnement industriel ou dans la nature, reste un enjeu majeur pour l'évaluation du risque associé. Il s'agit d'un problème de société qui n'a pu malheureusement trouver de réponse dans les études épidémiologiques classiques dans la mesure où les quelques données fiables concernent plutôt des expositions accidentelles à des doses beaucoup plus élevées. L'exposition naturelle représente pourtant la première source dans la vie courante juste devant les sources d'origines médicales (radiologie, radiothérapie). Ce type d'exposition est très difficile à reproduire en laboratoire sur des lignées cellulaires. La méthode principalement utilisée, basée sur l'irradiation aléatoire de populations cellulaires, consiste à calculer le nombre moyen de particules ayant interagi par cellule et repose ainsi sur des lois de distribution statistique (loi de Poisson). En plus des inévitables impacts multiples, la variété des cibles intracellulaires touchées (noyau, cytoplasme), les effets indirects induits par les impacts sur les cellules voisines ou simplement extracellulaires sont autant de phénomènes qui compliquent alors sérieusement l'interprétation des données.<br /><br />Dans ce contexte, un microfaisceau de particules  a été développé au CENBG pour réaliser des irradiations ciblées à l'échelle sub-cellulaire avec une précision de quelques micromètres. Il est ainsi possible de contrôler le nombre exact de particules délivrées par cellule (jusqu'à la dose ultime d'un ion par cellule), de prédéterminer avec précision le point d'impact et d'irradier certaines cellules tout en vérifiant la réponse de cellules voisines.<br /><br />La validation de ce dispositif a été réalisée au cours de ce travail de thèse, sur des kératinocytes humains exprimant une protéine recombinante nucléaire fluorescente (histone H2B-GFP) en mettant en évidence des dommages nucléaires radio-induits spécifiques et dose-dépendant. La combinaison de techniques telles que le microfaisceau d'ions, la microscopie confocale et l'analyse quantitative numérique a permis de mesurer, in situ et à l'échelle de la cellule unique, la cinétique de phosphorylation de la protéine histone H2A.X et d'aborder ainsi l'étude des processus de réparation de l'ADN et d'induction de l'apoptose. Les résultats expérimentaux ont validé la méthodologie développée en démontrant la reproductibilité du tir et le contrôle de la dose grâce à la mise en évidence d'une relation dose-effet qui a été également étudiée en fonction du temps.

Submitted by Mario Lopes (mariosilvalopes@gmail.com) on 2011-11-17T22:51:02Z No. of bitstreams: 1 DissertaçãoMSLFinal.pdf: 2601229 bytes, checksum: 8dd97b22637c4e3c6b2b47dfcab63218 (MD5) / Approved for entry into archive by Gisele Isaura Hannickel (gisele.hannickel@fgv.br) on 2011-11-18T10:41:59Z (GMT) No. of bitstreams: 1 DissertaçãoMSLFinal.pdf: 2601229 bytes, checksum: 8dd97b22637c4e3c6b2b47dfcab63218 (MD5) / Made available in DSpace on 2011-11-18T10:43:55Z (GMT). No. of bitstreams: 1 DissertaçãoMSLFinal.pdf: 2601229 bytes, checksum: 8dd97b22637c4e3c6b2b47dfcab63218 (MD5) Previous issue date: 2011-10-24 / O funcionamento dos bancos comerciais implica no sucesso de suas estratégias de captação de depósitos a prazo. O Certificado de Depósito Bancário (CDB) é um dos instrumentos mais utilizados para este fim. 95% dos CDBs são flutuantes e atrelados ao CDI, sendo que grande parte destes CDBs tem data de carência pré-definida para o resgate. Esta característica é responsável pela opção implícita de resgate oferecida ao investidor. Ou seja, o investidor tem a prerrogativa de resgatar seu investimento entre a data de carência e o vencimento do CDB sem que seja penalizado por isso. Este trabalho apresenta um método de apreçamento da opção de resgate implícita no CDB utilizando o modelo de Black Derman Toy. A técnica empregada inova ao considerar o nível da estrutura a termo de taxa de juros tanto em relação à curva de CDBs observada no mercado, quanto a sua volatilidade. Entretanto, a volatilidade é preservada e, por isso, não é contaminada pelas oscilações da estrutura a termo. No procedimento foram utilizados os CDBs do banco de dados da Cetip com valores maiores que quinhentos mil reais emitidos entre 2007 e 2009. Assumiu-se que todos os investidores eram racionais e não precisaram recorrer aos seus investimentos, portanto só resgataram seus recursos após o fim do prazo de carência. Com o intuito de verificar a validade dos preços calculados através do modelo Black Derman Toy, foi aplicada a técnica da simulação de Monte Carlo com a criação de dez mil trajetórias para o preço do ativo. Os resultados obtidos através do modelo proposto foram confirmados quando confrontados com a simulação de Monte Carlo. / The functioning of commercial banks relies on the success of their strategies to attract deposits. Time Deposits (TD) are one of the most used for this purpose. 95% of TDs have floating rates linked to Interbank Certificate of Deposits (CDI) and most of them have a pre-set grace date to the withdrawal. This feature is responsible for the embedded option offered to the investor. That is, the investor has the right to withdrawal their investment between the grace date and the TD maturity without being penalized. This paper presents a method of pricing withdrawal implied options in TDs using Black Derman Toy model. The innovative technique considers the level of the interest rates term structure in relation to TDs curve observed on the market, as well as its volatility. However, volatility is preserved, and therefore is not contaminated by term structure oscillations. In the procedure were used TDs (Cetip database) with amounts greater than five hundred thousand Reais issued between 2007 and 2009. It was assumed that all investors were rational and did not need to rely on their investments, so only withdrew them after their grace period. In order to verify the validity of the calculated prices by Black Derman Toy Model, Monte Carlo simulation technique was applied with the creation of ten thousand asset trajectories. Results obtained by the proposed model were confirmed when confronted with Monte Carlo simulation