This thesis addresses the isotropic diffuse gamma-ray background, as measured by the Fermi gamma ray space telescope, and its implications for indirect detection of dark matter. We describe the measurement of the isotropic background, including also an alternative analysis method besides the one published by the Fermi-LAT collaboration. The measured isotropic diffuse background is compatible with a power law differential energy spectrum with a spectral index of  -2.41 ± 0.05 and -2.39 ± 0.08, for the two analysis methods respectively. This is a softer spectrum than previously reported by the EGRET experiment. This rules out any dominant contribution with a significantly different shape, e.g. from dark matter, in the energy range 20 MeV to 102.4 GeV. Instead we present upper limits on a signal originating from annihilating dark matter of extragalactic origin. The uncertainty in the dark matter signal is primarily dependent on the cosmological evolution of the dark matter distribution. We use recent N-body simulations of structure formation, as well as a semi-analytical calculation, to assess this uncertainty. We investigate three main annihilation channels and find that in some, but not in all, of our scenarios we can start to probe, and sometimes rule out, interesting parameter spaces of particle physics models beyond the standard model.We also investigate the possibility to use the angular anisotropies of the annihilation signal to separate it from a background originating from conventional sources, e.g. from active galactic nuclei. By carefully modelling the performance of the Fermi gamma-ray space telescope and galactic foregrounds we find that this method could be as sensitive as using information from the energy spectrum only. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript.</p>

Le moteur downsizé à allumage commandé constitue l’une des voies principales explorées par les constructeurs automobiles pour améliorer le rendement et réduire les émissions de dioxyde de carbone des motorisations essence. Il s’agit de combiner une réduction de la cylindrée avec une forte suralimentation afin d’améliorer le rendement du moteur, en particulier à faibles et moyennes charges. Leur mise au point est limitée par l’augmentation des combustions anormales, dont le contrôle par forte dilution peut également entraîner l'apparition de variabilités cycliques importantes. Actuellement, la compréhension des nombreux paramètres intervenant dans l'apparition de ces phénomènes et de leurs interactions, reste encore imparfaite. Dans ce contexte, l’objectif de ce travail est de contribuer à la compréhension des mécanismes impliqués dans les processus de propagation des flammes turbulentes. Cette étude est réalisée dans une enceinte de combustion sphérique haute pression haute température, équipée de ventilateurs générant une turbulence homogène et isotrope. La première partie de ce travail est consacrée à l’étude de la combustion prémélangée laminaire isooctane/air. Dans un deuxième temps, l’aérodynamique de l’écoulement dans l’enceinte est finement caractérisée par Vélocimétrie Laser Doppler et Vélocimétrie par Images de Particules. Enfin, la propagation des flammes turbulentes est étudiée en termes de vitesse à partir de visualisations par ombroscopie. Une loi unifiée, permettant de décrire la propagation des flammes turbulentes indépendamment des conditions thermodynamiques initiales, de l’intensité de la turbulence et de la nature du mélange réactif est notamment proposée. / Engine downsizing is a promising way explored for reducing carbon dioxide and pollutant emissions of spark ignition engines. Its principle is to reduce the engine size and to increase its specific power with the use of a turbocharger, especially at middle and high loads. Its development leads to the appearance of abnormal combustions, whose control by a high dilution rate can also lead to important cyclic variabilities. The understanding of the multiple parameters controlling these phenomena and their interactions, is still very limited. In this context, the present thesis addresses the issue related to the understanding of the mechanisms implied in turbulent flame propagation processes. This study is carried out in a fan-stirred high pressure high temperature spherical combustion vessel where turbulence is homogeneous and isotropic. The first part of this study concerns the study of laminar premixed flames of isooctane/air mixtures. Second, the turbulent flow in the vessel is accurately characterized using Laser Doppler Velocimetry and Particle Image Velocimetry measurements. Then, turbulent flame propagation is investigated in terms of flame velocity using shadowgraph visualizations. A unified scaling law for the turbulent propagation speed is especially proposed, regardless of the thermodynamic initial conditions, the intensity of the turbulence and the nature of the air/fuel mixture.

Galliform birds (Galliformes) make up together with anseriform birds (Anseriformes) the clade Galloanserae, the sister group of Neoaves and the most basal clade of Neognathae. However, to date no quantitative data on cellular composition of their brains have been available. Here, I used the isotropic fractionator to determine numbers of neurons and non-neuronal cells in specific brain regions of 15 species of galliform birds. I find that cellular scaling rules for galliforms differ starkly from those for songbirds and parrots. When compared to these crown avian lineages, galliform birds feature lower degree of encephalization, a proportionally smaller telencephalon, small telencephalic and dominant cerebellar neuronal fractions, generally lower neuronal densities and larger glia/neuron ratios. Consequently, their brains and especially their forebrains harbor much smaller absolute numbers of neurons than those of equivalently sized songbird and parrots, the fact that undoubtedly constrains cognitive abilities of galliforms. However, this not to say that galliform birds are "bird brains" with low numbers of neurons and a limited ability to learn. Because they have high neuronal densities, their relatively small brains contain about equal numbers of neurons as brains of equivalently sized rodents and...

Une des problématiques majeures dans l’industrie des bioprocédés réside dans l’extrapolation des procédés biologiques à grande échelle. On observe généralement à l’échelle industrielle des écarts de rendement de croissance de la biomasse, ainsi que la formation de sous-produits comparativement à l’échelle du laboratoire. La formation de gradients de concentration à l’échelle des bioréacteurs est souvent évoquée. Dans ce travail, les interactions entre micromélange et assimilation du substrat sont abordées à l’échelle du microorganisme. Un modèle couplant transport et assimilation à l’échelle d’un microorganisme est proposé. L’existence de régimes physique et biologique, limitant l’assimilation du substrat est mise en lumière. Une approche basée sur le suivi Lagrangien de particules dans un champ de turbulence homogène isotrope est ensuite retenue. Les effets des hétérogénéités de concentration vues par les microorganismes, sont traduits à l’échelle de la population entière. Une loi analytique permettant de construire la distribution de flux reçus par les microorganismes à partir de la distribution de concentration en substrat dans le fluide, est proposée. Partant de cette distribution de concentrations vues, l’adjonction d’un modèle métabolique simplifié permet d’expliquer les baisses de vitesse spécifiques de croissance et la formation de sous-produits observées expérimentalement. Enfin, de premiers résultats sur le couplage inverse biologique sont présentés. L’effet des microorganismes sur le champ de concentration est caractérisé et une étude paramétrique sur les propriétés dynamiques et biologiques est réalisée. / The scale-up of biological process is a critical issue in the bioprocess industry. When passing from a laboratory to an industrial scale, the conversion yield of substrate into biomass is often overestimated and by-products are formed. Different existing works attempt to predict the effect of mixing on biomass growth and the emergence of substrate concentration gradients at the reactor scale are a first explanation of the degraded performances. In this work the interactions between micro-mixing and substrate assimilation are addressed at the microorganism scale. A coupled transport-assimilation model is proposed for an isolated microorganism. The emergence of physical and biological regimes limiting the substrate assimilation is enlightened. An approach based on the Lagrangian tracking of microorganisms in a homogeneous isotropic turbulent field is then chosen. The effects of local concentration heterogeneities seen by microorganisms are observed at the population scale. An analytical expression is proposed for the assimilated substrate flux distribution by the microorganisms, based on the substrate concentration distribution in the fluid. From these concentrations encountered by microorganisms, we coupled a simplified metabolic model that explains the decreased specific growth rate, and the by-products formation often observed in many experiments. Finally, first results on the biological two-way coupling are proposed. The effect of microorganisms on the substrate field is characterised and a parametric study on the dynamics as well as biological parameters is realised.

Ácidos graxos são moléculas hidrofóbicas essenciais para a composição da estrutura física celular, para o metabolismo energético dos seres vivos e também para os caminhos de sinalização molecular no proteoma celular. No caso de deficiência no ácido graxo docosahexaenóico (DHA) e do ácido eicosapentaenoico (EPA) temos a depressão e a mudança do comportamento. O transporte destas moléculas hidrofóbicas no citosol celular é realizado por uma família de proteínas capazes de se ligar a esses ácidos graxos de maneira seletiva, com alta afinidade e de forma reversível. Esta família de proteína é conhecida como FABP, ou proteínas ligantes de ácido graxo. Para realizar esta função, as FABP possuem características únicas tanto na sua estrutura tridimensional quanto na dinâmica experimentada pelos vários elementos estruturais. Diversos trabalhos identificaram regiões relevantes e, com mutações realizadas em resíduos específicos, caracterizaram o mecanismo como a proteína interage com ligantes e com a bicamada lipídica para a realização da sua função, identificando um processo multi-estágio na interação com a bicamada lipídica. Contudo, a não realização de mutações em todos os resíduos da proteína pode deixar não-identificados regiões ou resíduos da proteína também envolvidos na sua função. Além disso, nunca foi caracterizado o que ocorre com os resíduos e com a estrutura da FABP quando a proteína está complexada com uma bicamada lipídica. No presente trabalho, escolhemos a B-FABP para estudar a interação com ligantes e o complexo proteína-membrana desta família de proteínas. Para isto, as técnicas de ressonância magnética nuclear 15N-HSQC e eletrônica (RMN e RPE) foram utilizadas para acompanhar mudanças estruturais e dinâmicas ocorridas quanto de interações moleculares. Com a técnica de RPE e o uso de derivados de ácidos graxos marcados com radicais nitróxidos, monitoramos o sítio de ligação da molécula de ácido graxo e suas alterações quando na presença do surfactante SDS. No caso de RMN, foi usada em proteínas marcadas isotopicamente com 15N na presença de bicelas isotrópicas de DMPC: DHPC na razão igual a um (q = 1), em uma concentração lipídica (CL) de 4%. Nossos resultados além de identificar os mesmos resíduos já conhecidos na interação da FABP com modelos de membrana, também encontrou novos resíduos nunca antes associados à superfície de contato da FABP com a bicamada lipídica. / Fatty acids are hydrophobic molecules essential to the cell structure, to the energetic metabolism of living organisms and to the molecular signaling pathways in the cell proteome. Depression and behavior alteations are two common consequences of deficiencies in docosahexanoic (DHA) and eicosapentaenoic (EPA) acids. The transport of such hydrophobic molecules in the cytosol is the main function of a family of proteins capable of making a selective, high affinity, and reversible binding of fatty acids. This family of proteins is known as FABPs (fatty acid binding proteins). To perform their function, FABPs have unique features in both their tridimensional structure and in the dynamics experienced by the several structural elements. Many reports have identified regions that are relevant to function and, through point mutations of specific residues, have characterized the mechanism used by the protein to bind its ligand and also to interact with lipid bilayers. However, the point mutation strategy relies heavily on the choice of residues such that missing residues can lead to the lack of identification of important elements involved in protein function. Moreover, the characterization of the protein-bilayer complex still deserves a more detailed investigation. In this work, we study the B-FABP protein in terms of its interaction with ligands as well as a membrane model system. We made use of magnetic resonance techniques, nuclear (NMR) and electronic (EPR), to probe structural and dynamical changes occurring upon intermolecular interaction. EPR and spin labeled fatty acids allowed us to monitor the ligand binding site in the protein structure and also its alterations in the presence of the surfactant SDS. NMR HSQC was used to gain information on the conformational changes of isotopically labeled protein in the presence of biceles made of DMPC:DHPC (q = 1 and lipid concentration CL of 4%). Our results confirmed relevant functional residues that had been previously identified and also pointed to new residues that had not been implicated as part of the contact surface before, thus widening our understanding of FABP-bilayer interaction.

Aplicamos a teoria de representação de funções isotrópicas para determinar o número mínimo de invariantes independentes necessários para caracterizar completamente a densidade de energia de deformação de sólido hiperelástico com duas direções de simetria material. Expressamos a densidade de energia em termos de dezoito invariantes e extraímos um conjunto de dez invariantes para analisar dois casos de simetria material. No caso de direções ortogonais, recuperamos o resultado clássico de sete invariantes e oferecemos uma justificativa para a escolha dos invariantes encontrados na literatura. Se as direções não são ortogonais, descobrimos que o número mínimo também é sete e corrigimos um erro em fórmula encontrada na literatura. Uma densidade de energia deste tipo é usada para modelar, na escala macroscópica, materiais de engenharia, tais como compósitos reforçados com fibras, e tecidos biológicos, tais como ossos. / We determine the minimum number of independent invariants that are needed to characterize completely the strain energy density of a hyperelastic solid having two distinct material symmetry directions. We use a theory of representation of isotropic functions to express this energy density in terms of eighteen invariants and extract a set of ten invariants to analyze two cases of material symmetry. In the case of orthogonal directions, we recover the classical result of seven invariants and offer a justification for the choice of invariants found in the literature. If the directions are not orthogonal, we find that the minimum number is also seven and correct a mistake in a formula found in the literature. An energy density of this type is used to model, on the macroscopic scale, engineering materials, such as fiber-reinforced composites, and biological tissues, such as bones.

Les écoulements turbulents de gaz denses, qui sont d’un grand intérêt pour un large éventail d'applications, sont le siège de phénomènes physiques encore peu connus et difficiles à étudier par des approches expérimentale. Dans ce travail, nous étudions pour la première fois l’influence des effets de gaz denses sur la structure de la turbulence compressible à l’aide de simulations numériques. Le fluide considéré est le PP11, un fluorocarbure lourd, dont le comportement thermodynamique a été représenté à l’aide de différentes lois d’état, afin de quantifier la sensibilité des solutions aux choix de modélisation. Nous avons considéré d’abord la décroissance d’une turbulence homogène isotrope compressible. Les fluctuations de température sont négligeables, alors que celles de la vitesse du son sont importantes à cause de leur forte dépendance de la densité. Le comportement particulier de la vitesse du son modifie de manière significative la structure de la turbulence, conduisant à la formation de shocklets de détente. L’analyse de la contribution des différentes structures à la dissipation d’énergie et à la génération d’enstrophie montre que, pour un gaz dense, les régions de forte dilatation jouent un rôle similaire à celles de forte compression, contrairement aux gaz parfaits, dans lesquels le comportement est fortement dissymétrique. Ensuite, nous avons mené des simulations numériques pour une configuration de canal plan en régime supersonique, pour plusieurs valeurs des nombres de Mach et de Reynolds. Les résultats confirment la validité de l’hypothèse de Morkovin. L’introduction d’une loi d’échelle semi-locale prenant en compte le variations de densité et viscosité, permet de comparer les profils des grandeurs turbulentes (contraintes de Reynolds, anisotropie, budgets d’énergie) avec ces observés en gaz parfait. Les variables thermodynamiques, quant à elles, présentent une évolution très différente pour un gaz parfait et pour un gaz dense, la chaleur spécifique élevée de ce dernier conduisant à un découplage des effets dynamiques et thermiques et à un comportement proche de celui d’un fluide incompressible avec des propriétés variables. / Dense gas turbulent flows, of great interest for a wide range of engineering applications, exhibit physical phenomena that are still poorly understood and difficult to reproduce experimentally. In this work, we study for the first time the influence of dense gas effects on the structure of compressible turbulence by means of numerical simulations. The fluid considered is PP11, a heavy fluorocarbon, whose thermodynamic behavior is described by means of different equations of state to quantify the sensitivity of solutions to modelling choices. First, we considered the decay of compressible homogeneous isotropic turbulence. Temperature fluctuations are found to be negligible, whereas those of the speed of sound are large because of the strong dependence on density. The peculiar behavior of the speed of sound significantly modifies the structure of the turbulence, leading to the occurrence of expansion shocklets. The analysis of the contribution of the different structures to energy dissipation and enstrophy generation shows that, for a dense gas, high expansion regions play a role similar to high compression ones, unlike perfect gases, in which the observed behaviour is highly asymmetric. Then, we carried out numerical simulations of a supersonic turbulent channel flow for several values of Mach and Reynolds numbers. The results confirm the validity of the Morkovin' hypothesis. The introduction of a semi-local scaling, taking into account density and viscosity variations across the channel, allow to compare the wall-normal profiles of turbulent quantities (Reynolds stresses, anisotropy, energy budgets) with those observed in ideal gases. Nevertheless, the thermodynamic variables exhibit a different evolution between perfect and dense gases, since the high specific heats of the latter lead to a decoupling of dynamic and thermal effects, and to a behavior close to that of variable property incompressible fluids.

Les méthodes de microscopie de super-résolution (SRM) telles que la microscopie PALM (photoactivated localization microscopy), STORM (stochastic optical reconstruction microscopy), BALM (binding-activated localization microscopy) et le DNA-PAINT, représentent un nouvel ensemble de techniques de microscopie optique qui permettent de surpasser la limite de diffraction ( > 200 nm dans le spectre visible). Ces méthodes sont basées sur la localisation de la fluorescence de molécules uniques, et peuvent atteindre des résolutions de l'ordre du nanomètres (~20 nm latéralement et 50 nm axialement). Les techniques SRM ont un large spectre d'applications dans les domaines de la biologie et de la biophysique, rendant possible l'accès à l'information tant dynamique que structurale de structures connues ou non, in vivo et in vitro. Beaucoup d'efforts ont été fournis durant la dernière décennie afin d'élargir le potentiel de ces méthodes en développant des méthodes de localisation à la fois plus précise et plus rapide, d'améliorer la photophysique des fluorophores, de développer des algorithmes pour obtenir une information quantitative et augmenter la précision de localisation, etc. Cependant, très peu de méthodes ont été développées pour examiner l'hétérogénéité des images et extraire les informations statistiquement pertinent à partir de plusieurs milliers d'images individuelles super-résolues. Dans mon travail de thèse, je me suis spécifiquement attaquée à ces limitations en: (1) construisant des objets de dimensions nanométriques et de structures bien définies, avec la possibilité d'être adaptés aux besoins. Ces objets sont basés sur les origamis d'ADN. (2) développant des approches de marquage afin d'acquérir des images homogènes de ces objets. (3) implémentant des outils statistiques dans le but d'améliorer l'analyse et la validation d'images. Ces outils se basent sur des méthodes de reconstruction de molécules uniques communément appliquées aux reconstructions d'images de microscopie électronique. J'ai spécifiquement appliqué ces développements à la reconstruction de formes 3D de deux origamis d'ADN modèles (en une et trois dimensions). Je montre comment ces méthodes permettent la dissection de l'hétérogénéité de l'échantillon, et la combinaison d'images similaires afin d'améliorer le rapport signal sur bruit. La combinaison de différentes classes moyennes ont permis la reconstruction des formes tridimensionnelles des origamis d'ADN. Particulièrement, car cette méthode utilise la projection 2D de différentes vues d'une même structure, elle permet la récupération de résolutions isotropes en trois dimensions. Des fonctions spécifiques ont été adaptées à partir de méthodologies existantes afin de quantifier la fiabilité des reconstructions et de leur résolution. A l'avenir, ces développements seront utiles pour la reconstruction 3D de tous types d'objets biologiques pouvant être observés à haute résolution par des méthodologies dérivées de PALM, STORM ou PAINT. / Super resolution microscopy (SRM) methods such as photoactivated localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), binding-activated localization microscopy (BALM) and DNA-PAINT represent a new collection of light microscopy techniques that allow to overpass the diffraction limit barrier ( > 200 nm in the visible spectrum). These methods are based on the localization of bursts of fluorescence from single fluorophores, and can reach nanometer resolutions (~20 nm in lateral and 50 nm in axial direction, respectively). SRM techniques have a broad spectrum of applications in the field of biology and biophysics, allowing access to structural and dynamical information of known and unknown biological structures in vivo and in vitro. Many efforts have been made over the last decade to increase the potential of these methods by developing more precise and faster localization techniques, to improve fluorophore photophysics, to develop algorithms to obtain quantitative information and increase localization precision, etc. However, very few methods have been developed to dissect image heterogeneity and to extract statistically relevant information from thousands of individual super-resolved images. In my thesis, I specifically tackled these limitations by: (1) constructing objects with nanometer dimensions and well-defined structures with the possibility of be tailored to any need. These objects are based on DNA origami. (2) developing labeling approaches to homogeneously image these objects. These approaches are based on adaptations of BALM and DNA-PAINT microscopies. (3) implemented statistical tools to improve image analysis and validation. These tools are based on single-particle reconstruction methods commonly applied to image reconstruction in electron microscopy.I specifically applied these developments to reconstruct the 3D shape of two model DNA origami (in one and three dimensions). I show how this method permits the dissection of sample heterogeneity, and the combination of similar images in order to improve the signal-to-noise ratio. The combination of different average classes permitted the reconstruction of the three dimensional shape of DNA origami. Notably, because this method uses the 2D projections of different views of the same structure, it permits the recovery of isotropic resolutions in three dimensions. Specific functions were adapted from previous methodologies to quantify the reliability of the reconstructions and their resolution.In future, these developments will be helpful for the 3D reconstruction of any biological object that can be imaged at super resolution by PALM, STORM or PAINT-derived methodologies.

The social brain hypothesis (SBH) posits that complex social environments exert a major selection pressure driving the evolution of large brains and intelligence. The hypothesis was first proposed to explain the remarkable cognitive abilities of primates and has since been extended to other vertebrate groups and gained a substantial popularity. Nevertheless, the empirical support is equivocal in virtually every group where the hypothesis has been tested. In this thesis, the SBH is tested in the African mole-rats (Bathyergidae). Mole-rats share a subterranean mode of life and similar ecologies while covering the whole social spectrum, from solitary to "eusocial". The number of brain neurons is considered a better proxy for intelligence than relative or absolute brain size. Therefore, a novel approach, the isotropic fractionator, was used to estimate the total number of neurons and other cells in five brain parts (olfactory bulbs, cerebral cortex, cerebellum, diencephalon and basal ganglia, brain stem) of eleven bathyergid species. This simultaneously allows for examining if and how mole-rats differ from other rodents with respect to brain cellular scaling rules. We found that, contrary to expectations, mole-rats generally conform to these rules, with a few exceptions. They tend to have higher...

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