Understanding 3D genome structure is crucial to learn how chromatin folds and how genes are regulated through the spatial organization of regulatory elements. Various technologies have been developed to investigate genome architecture. These technologies include ligation-based 3C Methodologies such as Hi-C and Micro-C, ligation-based pull-down methods like Proximity Ligation-Assisted ChIP-seq (PLAC Seq) and Paired-end tag sequencing (ChIA PET), and ligation-free methods like Split-Pool Recognition of Interactions by Tag Extension (SPRITE) and Genome Architecture Mapping (GAM). Although these technologies have provided great insight into chromatin organization, a systematic evaluation of these technologies is lacking. Among these technologies, Hi-C has been one of the most widely used methods to map genome-wide chromatin interactions for over a decade. To understand how the choice of experimental parameters determines the ability to detect and quantify the features of chromosome folding, we have first systematically evaluated two critical parameters in the Hi-C protocol: cross-linking and digestion of chromatin. We found that different protocols capture distinct 3D genome features with different efficiencies depending on the cell type (Chapter 2). Use of the updated Hi-C protocol with new parameters, which we call Hi-C 3.0, was subsequently evaluated and found to provide the best loop detection compared to all previous Hi-C protocols as well as better compartment quantification compared to Micro-C (Chapter 3). Finally, to understand how the aforementioned technologies (Hi-C, Micro-C, PLAC-Seq, ChIA-PET, SPRITE, GAM) that measure 3D organization could provide a comprehensive understanding of the genome structure, we have performed a comparison of these technologies. We found that each of these methods captures different aspects of the chromatin folding (Chapter 4). Collectively, these studies suggest that improving the 3D methodologies and integrative analyses of these methods will reveal unprecedented details of the genome structure and function.

This thesis treats the findings and current theories of the active galactic nuclei 3454.3. It mainly aims to describe the behavior of the specific source in the gamma-ray energy band as recorded by the Fermi-LAT satellite. Using NASA’s computational tools and all recorded data the variability of the source was assessed. As the received flux from the source varies substantially over time several periods of time for which the flux differs considerably were analysed. Spectral analysis for the various time-frames was performed in order to determine how we best can describe the results from each period. The Fermi-LAT results were then examined in the wider context of multi-wavelength astronomy. Finally, data retrieved at all wavelengths were modeled and compared in accordance with currently held theories.

No description available.

Chez les mammifères, l'ADN des cellules interphasiques s'organise en une fibre chromatinienne confinée à l'intérieur de « territoires chromosomiques ». Ce confinement autorise l'établissement d'interactions à longue distance permettant une régulation fine des fonctions génomiques. Toutefois, l'organisation et la dynamique de la chromatine à l'échelle dite supranucléosomale (10 à 500 kb) reste méconnue. Afin d'étudier la chromatine à cette échelle, nous avons utilisé la méthode dite de 3C-qPCR qui permet de mesurer les fréquences d'interactions entre deux portions génomiques. Dans un premier temps, nous avons analysé les collisions aléatoires afin de déterminer l'organisation intrinsèque de la chromatine à l'échelle supranucléosomale. Nos résultats indiquent que, en l'absence d'interactions spécifiques, les collisions aléatoires dans les régions riches en gènes présentent une modulation d'une périodicité d'environ 90kb. Cette modulation semble être sous-jacente à de nombreuses interactions spécifiques et avoir des répercutions sur leur positionnement génomique contribuant ainsi à l'évolution des génomes. Des modèles, dérivés de la physique des polymères, suggèrent que la chromatine s'organise dans ces régions en une hélice statistique. Dans un second temps, nous avons abordé l'organisation tridimensionnelle du locus murin Igf2/H19 soumis à l'empreinte génomique parentale. Les interactions spécifiques identifiées entre des « enhancers » endodermiques et certaines portions du locus ont confirmé l'existence d'une hiérarchie des interactions et ont permis la découverte d'un nouveau locus soumis à l'empreinte (PIHit). Ce locus produit un ARN non codant que nous avons caractérisé mais dont la fonction exacte reste à déterminer.Finalement, mes travaux de thèse ont aussi conduit à la mise au point d'une nouvelle technologie (HRS-SEQ) qui permettra d'aborder l'organisation génomique globale par le biais des séquences récupérées à haut-sel (HRS). / In mammal, the DNA of interphasic cells is organized into the chromatin fiber which is itself confined inside “chromosome territories”. This compact organization allows the establishment of long-range interactions involved in the fine regulation of genomic processes. However, the organization and the dynamic of the chromatin at the so-called supranucleosomal scale (10 to 500kb) remain unclear. In order to study the chromatin at this scale, we used the 3C-qPCR method that allows to measure interaction frequencies between two genomic regions. Firstly, we have analyzed random collisions in order to determine the intrinsic organization of the chromatin at the supranucleosomal scale. Our data indicates that, in the absence of specific interactions, random collisions in gene-rich regions show a periodic modulation of about 90kb. This modulation seems to be underlying numerous locus-specific interactions and have repercussions on their genomic location, thus contributing to genome evolution. Models, derived from polymers physics, suggest that, in these regions, the chromatin is shaped in a statistical helix. Secondly, we have investigated the tridimensional organization of the Igf2/H19 mouse locus which is subject to genomic imprinting. Specific interactions identified between endodermic enhancers and some regions of the locus have confirmed the existence of a hierarchy of interactions and allowed the discovery of a new imprinted locus (PIHit). This locus produces a non-coding RNA that we have characterized but for which the function remains to be determined.Finally, my work also led to the development of a new technology (HRS-SEQ) that allows to study global genome organization through mapping of high-salt recovered sequences (HRS).

Dédié à l'étude du ciel en rayons gamma, le satellite Fermi comporte à son bord le Large Area Telescope (LAT), sensible au rayonnement gamma de 20 MeV à 300 GeV. Les données recueillies par le LAT depuis son lancement en 2008 ont permis de multiplier par 10 le nombre de noyaux actifs de galaxie (NAG) détectés dans le domaine du GeV. Les rayons gamma observés dans les NAGs proviennent de processus énergétiques faisant intervenir des particules chargées de très haute énergie. Ces particules sont confinées dans un jet de plasma magnétisé qui prend sa source dans une région proche du trou noir supermassif habitant la zone centrale de la galaxie hôte. Ce jet s’éloigne à des vitesses aussi élevées que 0.9999c, formant dans de nombreux cas des lobes radio sur des échelles du kiloparsec voire du mégaparsec. Les NAGs dont le jet fait un angle faible avec la ligne de visée sont appelés blazars. La combinaison de cette très faible inclinaison du jet par rapport à la ligne de visée et de vitesses d’éjection relativistes donne lieu à des effets relativistes : mouvements apparents superluminiques, amplification de la luminosité et modification des échelles de temps. Les blazars sont caractérisés par une extrême variabilité à toutes les longueurs d’onde, sur des échelles de temps allant de quelques minutes à plusieurs mois. Une étude temporelle et spectrale du plus brillant d'entre ceux détectés par le LAT, 3C 454.3, a été réalisée afin de contraindre les modèles d'émission. Une nouvelle méthode de génération de courbes de lumière à échantillonnage adaptatif est également proposée dans cette thèse. Celle-ci permet d'extraire le maximum d'information des données du LAT quel que soit l'état de flux de la source. / The Fermi Gamma-ray Space Telescope was launched on 2008 June 11, carrying the Large Area Telescope(LAT), sensitive to gamma-rays in the 20 MeV – 300 GeV energy range. The data collected since then allowed to multiply by a factor of 10 the number of Active Galactic Nuclei (AGN) detected in the GeV range. Gamma-rays observed in AGNs come from energetic precesses bringing into play very high energy charged particles. These particles are confined in a magnetized plasma jet rising in a region close to the supermassive black hole in the center of the host galaxy. This jet moves away with velocities as high as 0.9999c, forming in many cases radio lobes on kiloparsec or even megaparsec scales. Among the AGNs, those whose jet inclination angle to the line of sight is small are called blazars. The combination of this small inclination angle with relativistic ejection speeds leds to relativistic effects : apparent superluminal motions, amplification of the luminosity and modification of the time scales. Blazars are characterized by extreme variability at all wavelengths, on time scales from a few minutes to several months. A temporal and spectral study of the most luminous of those detected by the LAT, 3C 454.3, was done so as to constrain emission models. A new method for generating adaptive-binning lightcurves is also suggested in this thesis. It allows to extract the maximum of information from the LAT data whatever the flux state of the source.

L'utilisation récente d'une voie originale de croissance cristalline basée sur les mécanismes vapeur-liquide-solide (VLS) à partir d'un bain Ge-Si a permis des améliorations importantes de la qualité cristalline des couches minces hétéroépitaxiales de SiC-3C sur substrats sur substrat α-SiC(0001). Ce travail a pour but d'approfondir les connaissances sur cette technique de croissance, d'améliorer le procédé et de déterminer les propriétés du matériau élaboré. La première partie est dédiée à la compréhension et la maîtrise des différents mécanismes impliqués dans la croissance de SiC-3C par VLS. Cela a notamment permis la détermination des paramètres limitant la taille des échantillons et la démonstration des avantages à utiliser des alliages fondus contant 50 at% de Ge au lieu de 75 at%. Une étude de la croissance latérale sur substrats patternés a donné des indications intéressantes pouvant être intégrées dans le modèle d'élimination des macles. L'incorporation intentionnelle et non intentionnelle de dopants de type n et p pendant la croissance VLS a été suivie. Pour le dopage n, nous avons démontré l'existence d'un lien clair entre l'impureté N et la stabilisation du polytype SiC-3C. En outre, nous avons réussi à abaisser le dopage résiduel n des couches en dessous de 1x1017 cm-3. Pour le dopage p, le meilleur élément n'est pas le Ga mais l'Al, même s'il doit être ajouté à un alliage de type Si-Ge pour éviter l'homoépitaxie. Enfin, ces couches ont été caractérisées optiquement et électriquement par différentes techniques. Les mesures C-V et G-V ont permis d'estimer une concentration très faible (7×109 cm-2) de charges fixes dans l'oxyde SiO2 ainsi qu'une densité d'états d'interface aussi basse que 1.2×1010 cm-2eV-1 à 0.63 eV sous la bande de conduction. Ces valeurs record sont une très bonne base pour le développement d'un composant de type MOSFET en SiC-3C / Recently, the use of an original growth approach based on vapour-liquid-solid (VLS) mechanism with Ge-Si melts has led to significant improvement of the crystalline quality of the 3C-SiC thin layers heteroepitaxially grown on α-SiC(0001) substrate. This work tries to deepen the knowledge of such specific growth method, to improve the process and to determine the properties of the grown material. The first part was dedicated to the understanding and mastering of the various mechanisms involved in 3C-SiC growth by VLS mechanism. This led to the determination of the parameters limiting sample size and the demonstration of the benefits of using 50 at% Ge instead of 75 at% Ge melts. A study of lateral enlargement on patterned substrates gave some interesting hints which can be integrated in the model of twin defect elimination. The incorporation of non intentional and intentional n- and p-type dopants during VLS growth was studied. For n-type doping, a clear link between N impurity and 3C polytype stability was demonstrated. Besides, high purity layers with residual n-type doping below 1x1017 cm-3 were achieved. For p-type doping, the best element was shown to be Al and not Ga, even if it has to be alloyed with Ge-Si melts to avoid homoepitaxial growth. Finally, these layers were characterised by several optical and electrical means like Raman spectroscopy, low temperature photoluminescence, deep leveltransient spectroscopy and MOS capacitors measurements. Very low concentrationsof fixed oxide charges estimated about 7×109 cm-2 and interface states densities Dit equal to 1.2×1010 cm-2eV-1at 0.63 eV below the conduction band have been achieved. These record values are a very good base toward 3C-SiC MOSFET

A Web 2.0 alterou o desenvolvimento de aplicações para internet. Contudo, os pesquisadores e desenvolvedores ainda replicam as ideias uns dos outros com pouco reuso. Esse cenário ilustra a necessidade de uma engenharia de domínio, na qual as similaridades e as variabilidades de uma família de aplicações são identificadas e documentadas, com a finalidade de obter o reuso dos componentes desenvolvidos. Neste trabalho, e feita uma engenharia de domínio para Redes Sociais na Web 2.0, com o foco nas funcionalidades colaborativas relativas ao compartilhamento de conteúdo. Como método, e utilizado o FODA (Feature Oriented Domain Analysis) adaptado com o modelo 3C de colaboração para classificar e padrões para interação mediada por computador para descrever as funcionalidades colaborativas. No modelo 3C, a colaboração e analisada a partir da comunicação, coordenação e cooperacao, e padroes descrevem e detalham o contexto de uso das funcionalidades levantadas. Para a implementação das funcionalidades colaborativas comuns nessas aplicações, são desenvolvidos componentes de software compatíveis com a plataforma Groupware Workbench. Um experimento foi realizado para avaliar os artefatos gerados na engenharia de domínio e um estudo de caso para avaliar a aplicabilidade e abrangência dos componentes desenvolvidos em um contexto real, a rede social para compartilhamento de imagens de arquitetura, chamada Arquigrafia Brasil. Os experimentos e o estudo de caso indicaram que os artefatos gerados são reusáveis, uteis e abrangem boa parte das funcionalidades presentes nas redes sociais atuais. / The Web 2.0 changed the development of internet applications. However, researchers and developers replicate each other ideas with low reuse. This scenario illustrates the necessity of a domain engineering, in which the communalities and variabilities of a family of applications are identified and documented. In this work, a domain engineering was applied on social networks in Web 2.0, focusing on collaborative features related to content sharing. We used, as a method, the FODA (Feature Oriented Domain Analysis) adapted with 3C collaboration model to classify and patterns for computer-mediated interaction to describe the collaborative features. To implement the commons features of these applications, a component kit compatible with an infrastructure named Groupware Workbench was defined and developed. An experiment was done to evaluate the artifacts generated by the domain engineering and a case study was done to evaluate coverage and applicability of the developed components in a real context, a social network for architectural images sharing named Arquigrafia Brasil. The experiment and the case study showed that the generated artifacts are reusable, useful and cover a representative part of the social networks collaborative features.

A tecnologia de componentes de software é propícia para encapsular questões técnicas de implementação e favorecer o reúso entre aplicações, o que é particularmente relevante no desenvolvimento de aplicações colaborativas na Web. Este trabalho utiliza a plataforma Groupware Workbench nesse contexto. A aplicação social Arquigrafia foi a principal motivadora dessa evolução. O Arquigrafia é um ambiente colaborativo para o estudo de arquitetura e compartilhamento de imagens fortemente baseado em colaboração e inteligência coletiva. Como o conceito de inteligência coletiva é muito amplo e mal definido, foi realizada uma análise de domínio e uma classificação das técnicas e seus usos nos sistemas atuais. Também foi feito o mapeamento e a implementação das funcionalidades do Arquigrafia em componentes do Groupware Workbench e executada uma avaliação da plataforma em quatro vertentes, sendo elas: arquitetura de componentes; suporte à colaboração; arquitetura técnica; e percepção dos desenvolvedores. Limitações tecnológicas e conceituais foram identificadas, como por exemplo, o modelo de mapeamento objeto-relacional e questões ligadas à flexibilidade. Essas limitações e colocações foram tratadas e avaliadas na plataforma, resultando em melhorias na arquitetura dos componentes e na simplificação do código. O Groupware Workbench no geral mostrou-se viável para o desenvolvimento de uma aplicação colaborativa real na Web 2.0. / Software components technology is favorable to encapsulate implementation technical issues and encourage the reuse among applications. These characteristics are particularly relevant in the development of web-based collaborative applications. This work evaluates and evolves the Groupware Workbench platform in this context. The social application Arquigrafia was the main motivation for this evolution. Arquigrafia is a collaborative environment for the study of architecture and image sharing strongly based on collaboration and collective intelligence. Since the concept of collective intelligence is very broad, we performed a domain analysis and a classification of its use in current systems. We also implemented the Arquigrafia features using Groupware Workbench components and evaluated the platform in four areas: components architecture; collaboration support; technical architecture; and developers perspective. We identified technological and conceptual limitations, as for example, the adopted object-relational mapping model and issues related to the flexibility of the platform. These limitations were treated and evaluated. We noted improvements in the architecture of the components and code simplification. As a result, the Groupware Workbench was a feasible solution for developing the Arquigrafia application.

L'étude concerne les couches limites turbulentes dans le cas d'écoulements à surface libre sur fond rugueux homogène. Afin de réaliser cette étude, deux dispositifs de mesure PIV par stéréoscopie (PIV 2D-3C) ont été mis en place avec comme double objectif de fournir les lignes directrices au design d'un système stéréoscopique PIV in situ et d'étudier l'influence de la faible submersion des éléments rugueux sur la structure universelle de la couche limite sur fond rugueux, i.e. pour des submersions h/D comprises entre 0,33 et 0,66 (avec h la hauteur des rugosités et D la hauteur d'eau). Pour le premier objectif, le dispositif de mesure a permis un accès optique facilité par un point de vue incliné des caméras à la zone proche des rugosités dans des conditions naturelles d'écoulement (turbidité et éclairement naturels). Les mesures de vitesse ont été faites dans un canal hydraulique de petite dimension (12 m x 0,5 m x 0,25 m) rempli d'hémisphères positionnées en quinconce. Une étude paramétrique de l'influence de l'inclinaison des caméras ainsi que de la turbidité de l'eau sur la qualité des mesures de vitesse a été entreprise suivie par une nouvelle méthodologie basée sur l'analyse de l'intensité lumineuse dans le système. Il a été montré que l'écoulement est correctement résolu jusqu'à une turbidité d'environ 25 NTU avec un angle d'inclinaison par rapport au plan vertical de mesure de 25°. Pour le second objectif, les investigations expérimentales ont été réalisées dans une veine hydraulique de plus grande dimension (26 m x 1,10 m x 0,50 m), dont le fond rugueux est constitué par des cubes en PVC de 2 cm de côté comme dans l'étude de Florens et al. (2013). Les résultats mettent en évidence que l'étendue de la sous-couche rugueuse augmente avec la submersion pour finalement occuper toute la colonne d'eau dans le cas de la plus faible submersion (h/D=0,66). Malgré cela, une loi logarithmique est tout de même observée, et ce, quelle que soit la submersion étudiée. / This work deals with turbulent boundary layers in open-channel flows over rough homogeneous beds. The objectives of this work are, first, to provide some guidance for the design of an efficient in situ stereoscopic PIV measurements system (SPIV), and, second, to assess the effect of the relative submergence on the universal turbulent boundary layer structure for very high relative submergence ratios, i:e: 0.33 < h/D <0.66 (where h is the roughness height and D the water depth). For the first objective, a stereoscopic PIV configuration was set-up with steeply inclined camera viewpoints in order to improve the image quality and the optical access into the bed canopy under naturally occurring turbid conditions. Velocity measurements were undertaken in a 12 m x 0.5 m x 0.25 m open-channel flume filled with staggered hemispheres as surrogates for bed river peebles. A parametric study was then carried out to both analyze how the turbidity and camera angle impact the quality of PIV measurements. An innovative light intensity-based methodology was developed and applied to perform data analysis. The latter shows good PIV results up to 25 NTU with an optimal camera angle with respect to the vertical PIV measurements plane of 25. The SPIV measurements for the second objective were performed in a 26-m-long, 1.10-m-wide and 0.50-m-deep steep open channel filled with 2-cm cubes as in Florens et al. (2013). The results show that the extent of the roughness sublayer increases with the relative submergence to fill the entire water column for the highest relative submergence investigated. Despite this, the logarithmic law is still observed even for the highest relative submergence studied (h/D=0.66).

A Web 2.0 alterou o desenvolvimento de aplicações para internet. Contudo, os pesquisadores e desenvolvedores ainda replicam as ideias uns dos outros com pouco reuso. Esse cenário ilustra a necessidade de uma engenharia de domínio, na qual as similaridades e as variabilidades de uma família de aplicações são identificadas e documentadas, com a finalidade de obter o reuso dos componentes desenvolvidos. Neste trabalho, e feita uma engenharia de domínio para Redes Sociais na Web 2.0, com o foco nas funcionalidades colaborativas relativas ao compartilhamento de conteúdo. Como método, e utilizado o FODA (Feature Oriented Domain Analysis) adaptado com o modelo 3C de colaboração para classificar e padrões para interação mediada por computador para descrever as funcionalidades colaborativas. No modelo 3C, a colaboração e analisada a partir da comunicação, coordenação e cooperacao, e padroes descrevem e detalham o contexto de uso das funcionalidades levantadas. Para a implementação das funcionalidades colaborativas comuns nessas aplicações, são desenvolvidos componentes de software compatíveis com a plataforma Groupware Workbench. Um experimento foi realizado para avaliar os artefatos gerados na engenharia de domínio e um estudo de caso para avaliar a aplicabilidade e abrangência dos componentes desenvolvidos em um contexto real, a rede social para compartilhamento de imagens de arquitetura, chamada Arquigrafia Brasil. Os experimentos e o estudo de caso indicaram que os artefatos gerados são reusáveis, uteis e abrangem boa parte das funcionalidades presentes nas redes sociais atuais. / The Web 2.0 changed the development of internet applications. However, researchers and developers replicate each other ideas with low reuse. This scenario illustrates the necessity of a domain engineering, in which the communalities and variabilities of a family of applications are identified and documented. In this work, a domain engineering was applied on social networks in Web 2.0, focusing on collaborative features related to content sharing. We used, as a method, the FODA (Feature Oriented Domain Analysis) adapted with 3C collaboration model to classify and patterns for computer-mediated interaction to describe the collaborative features. To implement the commons features of these applications, a component kit compatible with an infrastructure named Groupware Workbench was defined and developed. An experiment was done to evaluate the artifacts generated by the domain engineering and a case study was done to evaluate coverage and applicability of the developed components in a real context, a social network for architectural images sharing named Arquigrafia Brasil. The experiment and the case study showed that the generated artifacts are reusable, useful and cover a representative part of the social networks collaborative features.