Les sarcomes sont des tumeurs rares (environ 1% des cancers) des tissus mous. Leur rareté et leur hétérogénéité clinique rend la prise en charge des patients très difficile. Ainsi, il est nécessaire d'identifier et de comprendre les mécanismes de l'oncogenèse de ces tumeurs.Pour cela, notre équipe a analysé 106 sarcomes par CGH-array et puces d'expression afin d'identifier des gènes d'intérêt pour expliquer la biologie de ces tumeurs. Grâce à des analyses intégratives bio-informatiques, deux gènes candidats ont été identifiés : les gènes RCBTB1 et DMD, dont la perte génomique dans respectivement 41% et 15% des cas et la diminution d'expression sont significativement associées à l'évolution métastatique. Nos résultats montrent que la délétion de RCBTB1 est pronostique de l'évolution métastatique. Il semblerait que cela soit dû à la sensibilisation des cellules à certaines chimiothérapies, plus particulièrement le docétaxel, lorsque RCBTB1 est surexprimé. En effet, nous avons pu montrer qu'une surexpression de ce gène augmentait le pourcentage de cellules en mitose or, le docétaxel agissant uniquement en mitose, ceci explique la sensibilisation des cellules au docétaxel. Enfin, nous avons vérifié les effets de la sensibilisation au docétaxel in vivo, en étudiant la croissance tumorale après traitement en fonction de l'expression de RCBTB1.Concernant DMD, nos résultats obtenus par RNA-seq montrent que seules deux isoformes sont exprimées dans les tumeurs d'origine myogénique : Dp427 et Dp71. Cependant, dans environ 20% des tumeurs, nous observons une délétion ciblant spécifiquement l'isoforme Dp427. Etant donné que la délétion de Dp427 n'a pas d'effet sur l'agressivité des cellules, j'ai testé l'hypothèse selon laquelle Dp71 aurait un rôle oncogénique. Ainsi, l'inhibition de Dp71 révèle qu'elle est nécessaire à la croissance cellulaire et à la formation de clones, car son inhibition entraîne un blocage du cycle cellulaire en phase G2/M / Sarcomas are rare malignant tumors that form a heterogeneous group with numerous histotypes and molecular subtypes. Among them, sarcomas with complex genomic profiles displaying no specific and recurrent genetic alterations represent 50% of all soft tissue sarcomas, and poorly respond to systemic treatment. It is therefore needed to improve our understanding of the mechanisms involved in response to chemotherapy and ultimately find new therapeutic targets.One hundred and six sarcoma samples were analyzed by CGH and cDNA arrays in order to establish both genomic and transcriptomic data from each sample. This analysis highlighted RCBTB1 and DMD genes which are lost and down-regulated in 41% and 15% of cases respectively. Their lost are significantly associated with metastatic evolution.Our results show that the deletion of RCBTB1 is prognostic of the metastatic evolution. It appears that this is due to the sensitization of the cells to specific chemotherapies, more particularly docetaxel, when RCBTB1 is overexpressed. Indeed, we have showed that overexpression of this gene increased the percentage of cells in mitosis. Docetaxel acting only in mitosis, this explains the sensitization of cells to docetaxel. Finally, we validated the effects of docetaxel sensitization in vivo by studying tumor growth after treatment.Concerning DMD, our results obtained by RNA-sequencing show that only two isoforms are expressed in sarcomas with complex genomics: Dp427 and Dp71. However, in 20% of tumors, we observed a deletion specifically targeting the Dp427 isoform. Since the deletion of Dp427 did not affect aggressiveness of cells, I tested the hypothesis that Dp71 would have an oncogenic role. Thus, inhibition of Dp71 reveals that it is necessary for cell growth and for the formation of clones, because its inhibition results in blocking of the G2 / M phase cell cycle

The work performed in this thesis explores new ways of reducing the drag of ground vehicles. Specifically, the effect of plasma actuators are investigated numerically with the intention to delay separation around a half-cylinder, a geometry chosen to represent a simplified A-pillar of a truck. The plasma actuators have to be included in turbulent flow simulations. Therefore, emphasis is first put on finding a numerical model that can reproduce the effect of the plasma without increasing the computational cost. This effect is modeled through a body force term added to the Navier-Stokes equations. To determine the strength and spatial extent of this body force, optimization was performed to minimize the difference between experimental and simulated profiles of plasma induced velocity.  The plasma actuator model is thereafter used in Large Eddy Simulations (LES) of the flow around a half-cylinder at Reynolds number Re=65*10^3 and Re=32*10^3. Two types of actuation cases are performed. In the first case, a single actuator is used. In the second case, a pair of consecutive actuators are used, and their position on the half-cylinder is changed. It is found that a drag reduction of up to 10% is achievable. Moreover, the ideal location for actuation is determined to be near the separation point of the non-actuated flow.  Finally, dynamic mode decomposition (DMD) is investigated as a tool to extract coherent dynamic structures from a turbulent flow field. The DMD is first used to analyze a channel flow where pulsations are imposed at a known frequency. It is found that DMD gives similar results to phase averaging done at the oscillation frequency. However, the presence of turbulence noise hinders the ability to identify modes at higher harmonics. The DMD is also used to post-process the half-cylinder flow case. There, it is found that the spectrum of the wake is broadband. Nevertheless, modes within distinct frequency ranges are found to be located in distinct spatial regions. / Arbetet som utförts i denna avhandling undersöker nya sätt att minska luftmotstånd hos markfordon. Speciellt undersöks numeriskt effekten av plasmaaktuatorer med avsikten att uppnå fördröjd separation av strömningen kring en halvcylinder, en geometri vald för att representera en förenklad A-stolpe på en lastbil.  För att kunna utföra studien behöver plasmaaktuatorer kunna ingå i beräkningar av turbulenta strömningsfält. Därför undersöks först sätt för att hitta en numerisk modell som kan reproducera effekten av plasma utan att öka beräkningskostnad. Plasmaaktuatorn  modelleras i detta arbete genom att ett källterm adderas till Navier-Stokes ekvationer. För att bestämma styrkan och den rumsliga utbredningen hos källtermen, utförs en optimering för att minimera skillnaden mellan experimentella och simulerade profiler av plasma inducerad strömningshastighet.  Plasmaaktuatormodellen används därefter i Large Eddy Simulations (LES) för att beräkna strömningen kring en halvcylinder med Reynolds tal Re=65*10^3 och Re=32*10^3. Två typer av fall studeras. I det första fallet används en enda aktuator. I det andra fallet, är ett par på varandra följande aktuatorer placerade, där aktuatorernas position på halvcylinder ändras. Resultaten visar att en luftmotståndsminskning på upp till 10% kan erhållas. Den idealiska platsen för aktuatorn bedöms vara nära den punkt där strömningen utan aktuator separerar. Slutligen undersöks Dynamic Mode Decomposition (DMD) som ett verktyg för att extrahera koherenta dynamiska strukturer i en turbulent strömning. DMD används först för att analysera pulserande kanalströmning där pulsationen har en känd frekvens. Resultaten visar att DMD ger liknande resultat som då fas-medelvärdesbildning görs vid oscillationsfrekvensen. Förekomsten av turbulens buller hindrar dock möjligheten att identifiera moder vid högre övertoner. DMD används också för att analysera strömningen kring halv-cylindern. I avhandlingen visas att spektrat i vaken är bredbandigt men att även moder inom distinkta frekvensintervall fanns vara belägna i avgränsade områden i vaken. / <p>QC 20170117</p>

Stereolithography printing is one of the most popular 3D printing technologies. This printers use a UV light source for photopolymer curing and can be used for a wide range of applications with high precision and excellent print quality. Commercially available printers do not allow the modifications of the optical and mechanical parameters of the instrument. For this reason, a DLP printer has been designed to allow the optical system modifications and thus changing the printing field and resolution. Another advantage is the possibility to modify already designed mechanical parts. The DLP printer has been designed and tested. The recommended printer parameters settings are listed, which are based on the performed experiments.

L'épissage des ARN pré-messagers est une étape essentielle pour l'expression des gènes chez les eucaryotes supérieurs. La reconnaissance des exons par la machinerie d'épissage est réalisée grâce à différents éléments cis-régulateurs incluant les séquences consensus d'épissage et les séquences auxiliaires activatrices ou inhibitrices d'épissage. Le pré-ARNm représente une nouvelle cible thérapeutique pour le traitement des maladies génétiques. L'approche du saut d'exon thérapeutique, destinée à restaurer l'expression d'une protéine totalement ou partiellement fonctionnelle en interférant avec le processus d'épissage, suscite un grand intérêt notamment pour la dystrophie musculaire de Duchenne où la modification du transcrit permettrait d'obtenir une forme modérée de la maladie, la Dystrophie musculaire de Becker. Des oligonucléotides antisens sont utilisés pour masquer les signaux d'épissage de reconnaissance d'un exon par le spliceosome, et induire son excision (ou saut) du transcrit mature. La détermination de la meilleure séquence cible des AONs est une difficulté majeure de cette approche. Pour le gène DMD, nous avons pu établir grâce à des analyses bioinformatiques et statistiques combinées avec des tests fonctionnels utilisant des minigènes rapporteurs d'épissage, que le ciblage de motifs exoniques qui fixent le facteur d'épissage SF2/ASF permettait d'obtenir la meilleure efficacité des AONs. Par ailleurs, nous avons exploré la régulation de l'épissage des pseudoexons dans le gène DMD, et notamment les mécanismes conduisant à l'inclusion de ces séquences introniques dans le transcrit mature en condition pathologique. L'étude de deux cas exceptionnels d'activation de pseudoexons associée à des remaniements introniques rares (double délétion, inversion) élargit le spectre des mutations à l'origine de ces défauts d'épissage, et illustre le rôle encore mal connu des remaniements introniques en pathologie humaine. / Splicing of pre-messenger RNAs to mature transcripts is a crucial step in eukaryotic gene expression. The recognition of exon by the splicing machinery involves different cis-regulatory elements, including the splice site motifs and auxiliary sequences, which can act by stimulating or repressing splicing. The pre-mRNA represents a new therapeutic target for the treatment of genetic diseases. Notably, the exon skipping strategy is currently one of the most promising therapeutic approaches for the Duchenne muscular dystrophy. It intends to restore the expression of a partially functional protein by interfering with the splicing process, and converts the severe DMD phenotype into the moderate form of the disease, Becker muscular Dystrophy (BMD). Antisense oligonucleotides are used to mask the splicing signals involved in exon recognition by the spliceosome to induce its skipping from the mature transcript and restore an open reading frame. The determination of the best target sequence of the AONs is one of the major hurdles to overcome. For the DMD gene, a bioinformatic and statistical analysis combined with minigenes studies allowed us to establish that targeting binding sites for the splicing factor SF2/ASF maximizes the AONs efficiency. In a second part of this work, we investigated the splicing regulation of pseudoexons in the DMD gene, in particular the mechanisms leading to the inclusion of these intronic sequences in the mature transcript in pathological conditions. The study of two exceptional cases of pseudoexons activation associated with rare intronic rearrangements (double-deletions, inversion) expands the spectrum of missplicing mutations, and demonstrates the potential role of pure intronic rearrangements in human pathology.

As Distrofias Musculares Progressivas (DMPs) constituem um grupo de doenças genéticas caracterizadas por uma degeneração progressiva e irreversível da musculatura esquelética. Dentre as diferentes abordagens terapêuticas propostas para esse grupo de doenças, a terapia celular com células-tronco mesenquimais (CTMs) tem sido um foco importante de pesquisas. Muitos tipos de CTMs já foram descritas com o intuito de reconhecer qual o tipo ideal a ser usado em uma possível terapia celular para DMPs. Neste trabalho comparamos o potencial terapêutico de células-tronco de diferentes fontes obtidas de um mesmo doador. Escolhemos as células de pericito (CP) como ferramenta de estudo, uma vez que elas estão presentes em todos os tecidos irrigados por vasculatura. Isolamos pericitos de 4 tecidos da mesma doadora (endométrio, trompa, tecido adiposo e músculo). Em seguida, injetamos 1 milhão dessas células intraperitonialmente em camundongos Utrntm1KedDmdmdx/J (duplo knockout para o gene da distrofina e utrofina) semanalmente, por 8 semanas, e avaliamos a clínica e a sobrevida desses animais. Observamos que nas condições experimentais desse estudo, o potencial miogênico dessas células é insuficiente para ser utilizado como terapia regenerativa. Entretanto, apesar dos testes padronizados não detectarem nenhuma melhora clínica aparente, os animais tratado com pericitos de gordura mostraram uma curva de sobrevivência significativamente maior do que os controles não tratados. Como não houve diferenciação miogênica, esses resultados sugerem que os efeitos benéficos ocorreram através de liberação de fatores tróficos e imunoreguladores (efeito parácrino). É digno de nota que apesar das células serem todas derivadas de pericito e de uma mesma doadora o aumento de sobrevida só foi observado com células do tecido adiposo. Esses resultados indicam que o potencial terapêutico de CP difere de acordo com sua origem e que essa diferença não depende do genoma do doador. Esses resultados constituem um passo inicial, porém, valioso na compreensão do potencial de utilização dessas células em terapias / Progressive Muscular Disorders (PMDs) are a group of heterogeneous genetic diseases characterized by an irreversible degeneration of the muscle tissue due to mutation or absence of a protein. Among the many different available therapeutic approaches to treat PMDs, cell therapy using mesenchymal stem cells (MSCs) are one of the most studied ones. There are many types of MCSs described to date and the need to identify the best one suited to treat PMDs has yet to be addressed. In this thesis, we compared the therapeutic potential of different types of stem cells derived from the same donor. First, we chose pericytes as a tool of comparison, as this cell is unequivocally present in all vascularized tissues. We isolated pericytes of 4 different tissues from the same donor (endometrium, fallopian tubes, adipose tissue and muscle). We injected 1 million of these cells intraperitonially in Utrntm1KedDmdmdx/J mice (knockout for the dystrophin and utrophin gene) weekly for 8 weeks evaluating the clinical features and survival curve of these mice. We observed that, in the experimental conditions of this study, the myogenic potential of these cells is insufficient to be harnessed as therapy for regenerative purposes. However, despite the fact that the standardized tests did not detect any apparent clinical improvement, mice treated with pericytes derived from adipose tissue had a survival curve greater than control treated mice. As we could not observe any myogenic differentiation or cell engraftment, this results suggests that the beneficial effect observed could be due to the releasing of trophic and immune modulator factors (paracrine effect). It is noteworthy that despite all cells being derived from the same donor, the increase in life expectancy was only observed in pericytes derived from the adipose tissue. These results indicate that the therapeutic potential of pericytes differs according to their tissue of origin and the difference is not due to genetic differences. This is still preliminary data but it is valuable in understanding the therapeutic potential of these cells

La combustion prévaporisée prémélangée pauvre est une piste de choix pour réduire les émissions polluantes des moteurs d'avions mais peut conduire à l'apparition d'instabilités thermo-acoustiques. Afin d'améliorer la stabilité de telles flammes, l'étagement du combustible consiste à contrôler la distribution spatiale du carburant. Une telle procédure s'accompagne cependant d'une complexité accrue du système pouvant déboucher sur des phénomènes inattendus.Un brûleur à l'échelle de laboratoire alimenté par du dodécane liquide est utilisé dans cette thèse. Le combustible est injecté dans deux étages séparés, permettant ainsi de contrôler sa distribution. Cette particularité permet l'observation de différentes formes de flammes et notamment de points bistables pour lesquels deux flammes différentes peuvent exister malgré des conditions opératoires identiques.L'utilisation de diagnostics optiques à haute cadence (diffusion de Mie des gouttes de combustible et émission spontanée de la flamme) est couplée à des méthodes de post-traitement avancées comme la Décomposition en Modes Dynamiques. Ainsi, des mécanismes pilotant la stabilisation des flammes ainsi que leurs changements de forme sont proposés. Ils mettent notamment en lumière les interactions entre l'écoulement gazeux, les gouttes de combustible et la flamme. / A promising way to reduce jet engines pollutant emissions is the use of lean premixed prevaporized combustion but it tends to trigger thermo-acoustic instabilities. To improve the stability of these flames, a procedure called staging consists in splitting the fuel injection to control its spatial distribution. This however leads to an increased complexity and unexpected phenomena can occur.In the present work, a model gas turbine combustor fed with liquid dodecane is used. It is equipped with two fuel injection stages to control the fuel distribution in the burner. Different flame stabilizations can be observed and a bistable case where two flame shapes can exist for the same operating conditions is highlighted.High-speed optical diagnostics (fuel droplets Mie scatering and chemiluminescence measurements) are coupled with advanced post-processing methods like Dynamic Mode Decomposition. The results enable to propose mechanisms leading to flame stabilization and flame shape transitions. They show a strong interplay between the gaseous flow, the fuel droplets and the flame itself.

Les dystrophies musculaires de Duchenne (DMD) et de Becker (BMD) sont dues à des mutations dans le gène DMD codant la Dystrophine. De nombreux aspects des mécanismes pathophysiologiques de ces maladies ne sont pas encore expliqués. Nous nous sommes intéressés à l'étude d'ARN non-codants pouvant participer à ces processus. Une première étude a été centrée sur l’identification de micro-ARNs (miARNs) impliqués dans la régulation de l’oxyde nitrique synthase neuronale (nNOS) une protéine partenaire de la Dystrophine et associée à des caractéristiques de ces pathologies telles que la fatigabilité musculaire. 617 miARNs ont été criblés par Taqman Low Density Array dans des muscles de sujets sains et de patients BMDdel45-55. 4 miARNs candidats ont été sélectionnés de cette étude pour leur surexpression chez les patients BMDdel45-55 et leur capacité théorique à cibler nNOS. Des expériences de modulation de l’expression de ces miARNs dans des myoblastes humains sains ou dystrophiques nous ont permis d’identifier que le miR-708-5p et le miR-34-5p pouvaient cibler nNOS et moduler son expression.Un deuxième axe a été mené sur l’étude des longs ARNs non-codants (lncARNs). Les introns 44 et 55, qui bornent les exons 45 à 55 délétés chez les patients BMDdel45-55, sont de grandes régions contenant des lncARNs décrits comme régulant la Dystrophine. Les points de cassure introniques des mutations de ces patients n’étant pas décrites, nous avons supposé l’existence de profils de lncARNs différents. L’analyse de l’ADN de ces patients montre en effet des profils de lncARNs différents, révélant ainsi l’importance d’une étude plus précise des zones de délétion des patients BMDdel45-55. / Duchenne (DMD) and Becker (BMD) muscular dystrophies are due to mutations in DMD gene, encoding Dystrophin. Many aspects of pathophysiological mechanisms of these diseases are not yet well understood. We were interested in the study of non-coding RNAs that could be involved in these pathological processes. A first study focused on micro-RNAs (miRNAs) that could modulate expression of the neuronal nitric oxide synthase (nNOS), a partner of Dystrophin which is linked to pathological features as muscular fatigability. 617 miRNAs were screened by Taqman Low Density Array in muscle biopsies of healthy subjects or BMDdel45-55 patients. 4 candidate miRNAs were selected from this study since they were overexpressed in BMDdel45-55 patients and for their theoretical ability to target nNOS. Experiments modulating the expression of these miRNAs in healthy or dystrophic human myoblasts enabled us to identify that miR-708-5p and miR-34-5p could target nNOS and modulate its expression.A second axis was conducted on long non-coding RNA (lncRNA). Introns 44 and 55, which bound exons 45-55 deleted in BMDdel45-55 patients, are large regions containing lncRNAs described as regulating Dystrophin. Since intronic breakpoints of DMD mutations of these pateints were not described, we have assumed the existence of different profiles of lncRNAs. DNA analysis of these patients actually showed different lncRNAs profiles, thus revealing the significance of a more precise analysis of deletion areas in DMD gene of BMDdel45-55 patients.

No description available.

As Distrofias Musculares Progressivas (DMPs) constituem um grupo de doenças genéticas caracterizadas por uma degeneração progressiva e irreversível da musculatura esquelética. Dentre as diferentes abordagens terapêuticas propostas para esse grupo de doenças, a terapia celular com células-tronco mesenquimais (CTMs) tem sido um foco importante de pesquisas. Muitos tipos de CTMs já foram descritas com o intuito de reconhecer qual o tipo ideal a ser usado em uma possível terapia celular para DMPs. Neste trabalho comparamos o potencial terapêutico de células-tronco de diferentes fontes obtidas de um mesmo doador. Escolhemos as células de pericito (CP) como ferramenta de estudo, uma vez que elas estão presentes em todos os tecidos irrigados por vasculatura. Isolamos pericitos de 4 tecidos da mesma doadora (endométrio, trompa, tecido adiposo e músculo). Em seguida, injetamos 1 milhão dessas células intraperitonialmente em camundongos Utrntm1KedDmdmdx/J (duplo knockout para o gene da distrofina e utrofina) semanalmente, por 8 semanas, e avaliamos a clínica e a sobrevida desses animais. Observamos que nas condições experimentais desse estudo, o potencial miogênico dessas células é insuficiente para ser utilizado como terapia regenerativa. Entretanto, apesar dos testes padronizados não detectarem nenhuma melhora clínica aparente, os animais tratado com pericitos de gordura mostraram uma curva de sobrevivência significativamente maior do que os controles não tratados. Como não houve diferenciação miogênica, esses resultados sugerem que os efeitos benéficos ocorreram através de liberação de fatores tróficos e imunoreguladores (efeito parácrino). É digno de nota que apesar das células serem todas derivadas de pericito e de uma mesma doadora o aumento de sobrevida só foi observado com células do tecido adiposo. Esses resultados indicam que o potencial terapêutico de CP difere de acordo com sua origem e que essa diferença não depende do genoma do doador. Esses resultados constituem um passo inicial, porém, valioso na compreensão do potencial de utilização dessas células em terapias / Progressive Muscular Disorders (PMDs) are a group of heterogeneous genetic diseases characterized by an irreversible degeneration of the muscle tissue due to mutation or absence of a protein. Among the many different available therapeutic approaches to treat PMDs, cell therapy using mesenchymal stem cells (MSCs) are one of the most studied ones. There are many types of MCSs described to date and the need to identify the best one suited to treat PMDs has yet to be addressed. In this thesis, we compared the therapeutic potential of different types of stem cells derived from the same donor. First, we chose pericytes as a tool of comparison, as this cell is unequivocally present in all vascularized tissues. We isolated pericytes of 4 different tissues from the same donor (endometrium, fallopian tubes, adipose tissue and muscle). We injected 1 million of these cells intraperitonially in Utrntm1KedDmdmdx/J mice (knockout for the dystrophin and utrophin gene) weekly for 8 weeks evaluating the clinical features and survival curve of these mice. We observed that, in the experimental conditions of this study, the myogenic potential of these cells is insufficient to be harnessed as therapy for regenerative purposes. However, despite the fact that the standardized tests did not detect any apparent clinical improvement, mice treated with pericytes derived from adipose tissue had a survival curve greater than control treated mice. As we could not observe any myogenic differentiation or cell engraftment, this results suggests that the beneficial effect observed could be due to the releasing of trophic and immune modulator factors (paracrine effect). It is noteworthy that despite all cells being derived from the same donor, the increase in life expectancy was only observed in pericytes derived from the adipose tissue. These results indicate that the therapeutic potential of pericytes differs according to their tissue of origin and the difference is not due to genetic differences. This is still preliminary data but it is valuable in understanding the therapeutic potential of these cells

Afin de concevoir des systèmes de propulsion innovants, l'amélioration des performances des prises d'air supersonique constitue un enjeu majeur. En particulier, les écoulements intervenant au sein des entrées d'air et/ou de diffuseurs supersoniques mettent en jeu des phénomènes complexes associés aux diverses échelles spatiales et temporelles: dynamique de la turbulence pariétale, interaction entre une onde de choc et une couche limite turbulente, décollements tridimensionnels et effets de coins. Malgré les contributions significatives et récentes des simulations numériques de haute fidélité sur les instationnarités de l'interaction onde de choc/couche limite sans paroi latérales, peu d'études numériques ont été menées sur l'influence des coins dans la dynamique de l'écoulement. En présence de parois latérales et à des nombres de Mach suffisamment élevés, l’interaction se modifie et un train de choc se forme dans le diffuseur. Dans le cadre de cette thèse, les équations de Navier-Stokes en régime compressible sont résolues à l'aide de schémas d'ordre élevé. Des simulations en régime supersonique de l'écoulement dans des diffuseurs rectangulaires de largeurs différentes sont effectuées. L'étude permet la mise en évidence de l'influence du confinement et des effets de coins. Une deuxième partie de l’étude est consacrée à la compréhension des instationnarités générées par un train de choc dans un diffuseur rectangulaire à l'aide d'outils de post-traitement avancés: décomposition modale dynamique et périodogramme. Les résultats montrent la présence d'un possible phénomène de résonance du diffuseur à des fréquences proches de celles émises par l'écoulement. / To design innovative propulsion systems, improving the performance of supersonic air intakes is a major issue. In particular, the flows through the air intakes and/or supersonic diffusers involve complex unsteady phenomena associated with various spatial and temporal scales such as: wall-bounded turbulence dynamics, interaction between a shock-wave and a turbulent boundary layer, three-dimensional separated flows and corners effects. Despite the significant contributions from recent high-fidelity simulations of unsteady shock-wave boundary layer interaction in the absence of side walls, few numerical studies were conducted with secondary flows due to corner effects. In the presence of side walls and at Mach numbers large enough, the topology of the interaction is modified and a shock-train forms in the diffuser. In this thesis, the Navier-Stokes compressible equations are solved using high-order schemes. Simulations of supersonic flows in rectangular diffusers of different widths are carried out. The study allows to highlight the influence of confinement and corners effects on the mean flow. A second part of the study is devoted to the understanding of the unsteadiness associated with a shock-train in a rectangular supersonic diffuser. For that purpose, advanced post-processing tools have been developed such as: dynamic mode decomposition and Fourier analysis. The results show the presence of a possible resonance phenomenon in the diffuser at frequencies close to those associated with the flow.