Cette thèse montre que l’on peut trouver chez Marx, Veblen et Hawtrey trois théories pré-keynésiennes de l’instabilité financière. Elle dégage, pour chacun d’eux, le cadre théorique qu’il met en place et qui lui permet de poser la question du rôle de la finance dans la dynamique économique. Elle analyse ensuite leurs écrits pour montrer que l’on peut en déduire des théories (incomplètes) de l’instabilité financière, c’est-à-dire que les perturbations économiques sont dues à la manière dont les entreprises se financent. Le chapitre I reconstruit la théorie marxienne des marchés financiers, ce qui permet, dans le chapitre II, de montrer le rôle central joué par la finance dans l’explication du cycle économique chez Marx. Le chapitre III dégage les éléments qui font de la théorie de Veblen une théorie du capitalisme financier, puis, dans le chapitre IV, discute cette dernière pour montrer qu’il s’agit d’une théorie de l’instabilité financière. Le chapitre V propose une représentation du modèle macroéconomique de Hawtrey, à partir de laquelle le chapitre VI dégage les conditions dans lesquelles le crédit est instable dans sa théorie. Le chapitre VII fait le lien entre les théories de ces auteurs et les faits économiques dont la connaissance a nourri leur réflexion : les théories de l’instabilité financière sont à la fois une explication, une représentation et un projet de régulation du capitalisme financier / The thesis demonstrates that three pre-keynesians theories of financial instability can be found in Marx, Veblen and Hawtrey. For each of these three authors, the argument is that the theoretical frame displayed allows him question the role of finance in the economic dynamic. Then, analysis of their main writings shows that theories of financial instability can be infered from them. In chapter I, the marxian theory of financial markets is reconstituted paving the way to the demonstration of the central role played by finance in the explanation of the business cycle in Marx’s theory in Chapter 2. In Chapter III, we show what elements in Veblen’s theory constitutes a theory of finance capitalism. Then, the discussion in Chapter IV shows how it a theory of financial instability. In Chapter V is displayed a representation of of Hawtrey’s macro-model. Chapter VI highlights the conditions under which credit is unstable in his theory. Chapter VII shows the links between the three authors’ theories and the economic facts that nurtured their thinking. It shows that their theories of financial instability are an explanation, a representation et a project of regulation of financial capitalism.

​ Nombreuses stratégies de contrôle ont été récemment proposées par la communauté scientifique afin depouvoir réduire la traînée dans les écoulements pariétaux. Entre autres, les Surfaces Superhydrophobes (SHS) ontmontré leurs capacités de pouvoir réduire considérablement le frottement pariétal d’un écoulement liquide grâce à laprésence de microbulles de gaz piégées dans les nano-rugosités de la surface. Dans des conditions géométrique etthermodynamique données pour lesquelles la transition de mouillage est évitée (condition pour laquelle normalementla taille des rugosités qui caractérise la SHS est de plusieurs ordres de grandeur plus petite que l'échellecaractéristique de l'écoulement principal), on peut atteindre ce qu’on appelle ‘l'effet Lotus’, pour lequel l'écoulementglisse à la paroi, avec une vitesse différente de zéro.. Dans ce cadre, nous nous sommes proposés d’étudier, à l’aidede simulations numériques l’influence des SHS sur la transition laminaire-turbulent dans un écoulement de canal.Pour cela, nous avons réalisé une série de simulations numériques directes (DNS), allant de l'état laminaire au casturbulent pleinement développé, en traitant la plupart de scénarios de transition connu en littérature. Des analyses destabilité locale et globale ont aussi été réalisées afin de déterminer l’influence de ces surfaces sur la première phasedu processus de transition. Bien que la procédure de déclenchement de la transition contrôlée (type K, H, C,...) soitbien décrite dans la littérature, cela n’est pas le cas pour les transitions naturelles. À cette fin, une nouvelle méthode aété développée pour déclencher puis étudier la transition naturelle dans des écoulements de type canal. Cette méthodeest basée sur des mécanismes de réceptivité de l'écoulement (resolvent global) permettant de construire un forçagevolumique spécifique. Plusieurs approches pour modéliser les SHS ont été utilisées, de complexités croissantes, touten tenant en compte des caractéristiques physiques de ces surfaces. Dans un premier temps, une condition deglissement homogène a été utilisée et son influence analysée. Chaque rugosité a été ensuite discrétisée spatialement,d’abord avec une alternance de condition limite sur une surface plate, ensuite en tenant compte de la dynamique del’interface gaz-liquide par une méthode Lagrangienne-Eulerienne Arbitraire (ALE). Nous avons montré que les SHSpermettent d’efficacement retarder les transitions contrôlées mais qu’en revanche elles ont peu d’influence sur lestransitions naturelles (développant des stries de vitesse). En effet, ce comportement dérive de l'équilibre entre deuxeffets contradictoires. D’un côté, le glissement pariétal nuit au développement des structures cohérentes de typehairpin ​ , en altérant le processus de ​ vortex stretching-tilting ​ . D’autre part, le mouvement de l’interface gaz-liquideinteragit avec les structures cohérentes de l'écoulement, en produisant des vitesses normales à la paroi favorisantdavantage le processus de ​ sweep-ejection et entraînant le développement de structures en forme d’arche. Nous avonsmontré que les interfaces gaz-liquide statiques retardent la transition de façon analogue à une condition aux limiteshomogène (si l’hétérogénéité pariétale est petite). En revanche la prise en compte de leur dynamique limite le retardde la transition, montrant l’importance du modèle de SHS dans les écoulements transitionnels. / Many passive control strategies have been recently proposed for reducing drag in wall-bounded shearflows. Among them, underwater SuperHydrophobic Surfaces (SHS) have proven to be capable of dramaticallyreducing the skin friction of a liquid flowing on top of them, due to the presence of gas bubbles trapped within thesurface nano-sculptures. In specific geometrical and thermodynamical conditions for which wetting transition isavoided (in particular, when the roughness elements characterizing the SHS are several orders of magnitude smallerthan the overlying flow), the so-called ’Lotus effect’ is achieved, for which the flow appears to slip on the surfacewith a non zero velocity. In this framework, we propose to study, by means of numerical simulations, the influence ofSHS on laminar-turbulent transition in a channel flow. To do so we have performed a series of direct numericalsimulations (DNS), from the laminar to the fully turbulent state, covering the majority of transition scenarios knownin the literature, as well as local and global stability analysis so to determine the influence of SHS onto the initialstages of the process. While the conditions for observing controlled K-type transition in a temporal channel flow arewell defined, this is not the case for uncontrolled ones. To this end, a novel theoretical numerical framework has beendeveloped so to enable the observation of natural transition in wall-bounded flows. This method, similarly to theFree-Stream-Turbulence framework available for the boundary layer flow, is capable of triggering uncontrolledtransition t​ hrough flow receptivity to a purpose-built forcing. Different surface modellings for the superhydrophobicsurfaces are tested. First, homogeneous slip conditions are used. Then, the spatial heterogeneity of the SHS has beenconsidered by modelling it as a flat surface with alternating slip no-slip boundary conditions. Finally, the dynamics ofeach microscopic liquid-gas free-surface has been taken into account by means of a fully coupled fluid-structuresolver, using an Arbitrary Lagrangian Eulerian formulation. We show that while SHS are ineffective in controllingtransition in noisy environment​ , they can strongly delay transition to turbulence for the K-type scenario​ . Thisbehaviour results from the balance of two opposing effects. On one hand slippery surfaces inhibit the development ofcharacteristic hairpin vortices by altering the vortex stretching-tilting process. On the other hand, the movement ofthe gas-liquid free-surfaces interacts with the overlying coherent structures, producing wall-normal velocities thatenhance the sweep-ejection process, leading to a rapid formation of hairpin-like head vortices. Thus, whenconsidering flat interfaces transition time is strongly increased, while taking into account the interface dynamicsinduces smaller changes with respect to the no-slip case, indicating the need for an appropriate modelling of SHS fortransition delay purposes.

Cette thèse est consacrée à l’étude de la turbulence homogène stratifiée instable, un écoulement idéalisé décrivant l’évolution de la turbulence au sein d’une zone de mélange de type Rayleigh-Taylor. Cette approche se concentre sur l’évolution des quantités fluctuantes ;l’influence de l’écoulement moyen est prise en compte au travers d’un gradient moyen de densité. Un modèle spectral est utilisé pour étudier cette turbulence, conjointement à des simulations numériques directes. En comparaison avec ces simulations, l’étape de validation du modèle met en lumière le rôle des termes de stratification sur la dynamique du transfert d’énergie. Une première étude montre l’établissement, dans l’état autosemblable, de lois d’échelles ainsi que l’influence de la distribution initiale d’énergie sur l’état asymptotique et sur l’anisotropie de l’écoulement. Dans une seconde étude, la rétroaction de la turbulence sur le gradient moyen est introduite, dans un premier temps, afin de rapprocher la dynamique autosemblable de la turbulence homogène stratifiée instable de celle observée en turbulence Rayleigh-Taylor. Dans un second temps, l’influence d’un renversement de la stratification sur la dynamique du mélange est étudiée au travers d’un profil d’accélération variable. / This thesis is dedicated to the study of unstably stratified homogeneous turbulence.This flow is an idealized framework introduced to investigate the turbulence developing at the centerline of a Rayleigh-Taylor mixing zone. This approach focuses on turbulent quantities, when the mean flow acts on the turbulent field through a mean density gradient.A spectral model and direct numerical simulations are used to study this turbulent flow.The validation step reveals the role of stratification terms on the energy transfer dynamic.Then, a first study shows the emergence of scaling laws in the self-similar state, together with the large scale energy distribution impact on the asymptotic state and on the flow anisotropy. In a second study, the turbulent retroaction on the mean density gradient is introduced in order to bring unstably stratified homogeneous turbulence closer to theRayleigh-Taylor turbulence dynamics. This step leads to investigate the consequences of a stratification inversion on the mixing dynamics through a variable acceleration profile.

L’objet de cette thèse est de comprendre en quoi l’instabilité financière est un phénomène inhérent au cycle et en quoi la relation entre la politique monétaire et le secteur bancaire joue un rôle central dans son explication. Nous mettons en évidence de nouveaux canaux de transmission de la politique monétaire, notamment les canaux de la prise de risque et du capital bancaire. Une idée forte de la thèse est que le crédit productif est évincé dans les deux phases du cycle au profit des actifs risqués dans la phase ascendante et des valeurs refuge en phase descendante. Notre démarche est alors de construire un modèle théorique qui rend compte de cette problématique et dont les hypothèses s’appuient à la fois sur une revue de la littérature abondante et l’observation de faits stylisés. / The aim of the thesis is to analyze financial instability. This latter is explained by its link with the cycle and the relation between the monetary policy and the banking sector. We highlight new transmission mechanisms of the monetary policy, especially the risk taking channel and the bank capital channel. The principal idea of the thesis is an eviction of the productive credit in good and bad times. After a survey, we build a theoretical model to capture the reaction of the banking sector during the cycle.

La réplication de l’ADN est un phénomène physiologique essentiel à la transmission du patrimoine génétique mais est aussi une source importante de stress endogène. Le stress réplicatif peut conduire à une instabilité génomique et a été mis en évidence à une étape très précoce du développement tumoral et de la sénescence. La recombinaison homologue (RH) est un processus de réparation qui permet la prise en prise en charge du stress réplicatif. De ce fait, un défaut de RH devrait permettre de révéler les stress réplicatifs endogènes. Ainsi, une progression ralentie des fourches de réplication a été observée dans des cellules déficientes pour la RH (RH-), et ce en absence de tout traitement exogène (Daboussi 2008). De plus, de nombreux travaux ont mis en évidence la présence de défauts mitotiques dans les cellules RH-, en absence de tout traitement exogène (Griffin 2000; Kraakman-van der Zwet 2002; Bertrand 2003; Daboussi 2005; Laulier 2011; Rodrigue 2013). L’origine de ces défauts mitotiques spontanés reste peu claire. En effet, la RH étant un processus préférentiellement actif au cours des phases S et G2, le lien avec la mitose reste à éclaircir. Cette thèse a pour but de comprendre l’impact du stress réplicatif très faible ou endogène sur les phases post-réplicatives du cycle cellulaire. Dans un premier temps, je me suis intéressée à l’impact de ce stress sur la mitose. Les résultats obtenus montrent que le traitement des cellules contrôle à de très faibles doses d’hydroxyurée (HU) n’affecte pas la progression dans le cycle cellulaire mais induit cependant une diminution de la vitesse de réplication, comparable à celle observée dans les cellules RH-. De plus le traitement des cellules contrôle à des faibles doses d’HU induit l’apparition de défauts mitotiques, notamment des centrosomes surnuméraires, à la même fréquence que dans les cellules RH- non traitées. Inversement, l’ajout de précurseurs de nucléotides dans les cellules RH- permet de supprimer la diminution de la vitesse de réplication ainsi que les centrosomes mitotiques surnuméraires. Ainsi, un stress réplicatif subtil, qui n’impacte pas de façon détectable la progression dans les phases S et G2 du cycle cellulaire, ni l’entrée en mitose, cause cependant des défauts mitotiques sévères. De façon importante, les centrosomes mitotiques surnuméraires peuvent entrainer des mitoses multipolaires, impactant ainsi l’ensemble du génome. Ces données mettent en évidence la connexion qui existe entre la réplication des chromosomes et leur ségrégation. Dans un second temps, j’ai étudié l’impact du stress réplicatif faible ou endogène en phase G2. Cette étude a été réalisée en utilisant des cellules RH-, ainsi qu’un modèle d’induction de faible stress réplicatif après traitement à très faible dose d’HU. La présence de foyers pRPA-Ser33 en phase G2 a été observée dans ces deux modèles, mettant en évidence des zones de stress réplicatif. Après traitement à très faible dose d’HU, nous observons également la présence en phase G2 de foyers 53BP1 et RAD51 qui colocalisent partiellement avec les foyers pRPA-Ser33. L’analyse en spectrométrie de masse après co-immunoprécipitation de la protéine 53BP1 en phase G2 a permis d’établir un lien avec des protéines impliquées dans le contrôle de l’assemblage du fuseau mitotique ainsi que dans le points de contrôle mitotique, étayant ainsi le lien entre le stress réplicatif et les défauts mitotiques. Pour finir, l’immunoprécipitation de la chromatine liée à la protéine pRPA-Ser33 en phase G2, suivie d’un séquençage (ChIPseq), a permis de révéler l’absence d’enrichissement au niveau des sites fragiles communs et de mettre en évidence un enrichissement au niveau des régions promotrices de certains gènes, notamment de gènes impliqués dans la régulation du cycle cellulaire et de la mort cellulaire. Ces résultats soulignent le lien entre le stress réplicatif très faible ou endogène et l’instabilité chromosomique, qui peut mener à l’initiation tumorale. / DNA replication is a physiological process, essential for genetic information transmission but DNA replication is also an important source of endogenous stress. Replicative stress can lead to genomic instability and has been reported in early-stage malignancies and senescence. Homologous recombination is a repair process which can handle replicative stress. Therefore, a defect in homologous recombination could reveal endogenous replicative stresses. Consistently, a slow down in replication fork progression has been observed in homologous recombination deficient (HR-) cells, in absence of any exogenous treatment (Daboussi et al. 2008). In addition, several studies have shown the presence of mitotic defects in HR- cells, in absence of any exogenous treatment (Griffin 2000; Kraakman-van der Zwet 2002; Bertrand 2003; Daboussi 2005; Laulier et al. 2011; Rodrigue 2013). The origin of these spontaneous mitotic defects is still unclear. Indeed, homologous recombination is preferentially active in S and G2 phases thus, the link with mitosis remains to be elucidated. The aim of this thesis is to understand the impact of a low or endogenous replicative stress on post-replicative phases. First, I studied the impact of a low or endogenous replicative stress on mitosis. Control cells were treated with very low hydroxyurea doses, that did not affected cell cycle progression but did slow down the replication fork progression to the same level than unchallenged HR- cells. Importanntly, exposure of the control cells to these low hydroxyurea doses generated the same mitotic defects, notably extra centrosomes, and to the same extent than in untreated HR- cells. Reciprocally, supplying nucleotide precursors to HR- cells suppressed both their replication deceleration and mitotic extra centrosome phenotypes. Therefore, subtle replication stress that does not impact S and G2 phase progression nor the entry in mitosis, nevertheless causes severe mitotic defects. Importantly, mitotic extra centrosome can lead to multipolar mitosis and then impact the whole genome stability. These data highlight the crosstalk between chromosome replication and segregation. Secondly, I studied the impact of low or endogenous replicative stress on G2 phase. This study was done using HR- cells as well as control cells treated with very low HU doses to induce a very low replicative stress. In both of these models, the presence of pRPA-Ser33 foci was observed in G2 phase, highlighting replicative stress regions. After very low HU treatement, we observed 53BP1 and RAD51 foci in G2 phase. These foci partially colocalized with pRPA-Ser33 foci in G2 phase. Mass spectrometry analyse after 53BP1 coimmunoprecipitation allowed to etablish a link between proteins involved in mitotic spindle assembly control and in mitotic checkpoint. These data support the link between replicative stress and mitotic defects. Lastly, the immmunoprecipitation of the chromatin interacting with pRPA-Ser33 in G2 phase, followed by sequencing (ChIPseq) allowed to reveal the absence of common fragile site enrichment and to highlight an enrichment at promoter regions of genes involved in cell cycle and cell death regulation. These data underline the link between very low or endogenous replicative stress and chromosomal instability, which can lead to tumorigenesis.

Metodologias de sequenciamento do genoma total para investigação de diferentes tipos de câncer detectaram recentemente uma nova classe de alterações caóticas de DNA, denominada Chromothripsis. Este fenômeno de instabilidade genômica é relativamente comum em tumores de Osteossarcoma (OS), mas existem poucos estudos que expliquem esta conexão ou abordem suas causas e consequências. A presente tese iniciou-se com a re-análise de microarrays de dez amostras de OS pediátrico, previamente processadas pelo nosso laboratório, para avaliar a variação de número de cópias de DNA (CNVs). Usando ferramentas de detecção de padrões característicos de Chromothripsis (CTLPs), encontramos 3 amostras de OS com Chromothripsis , que afetaram quatro cromossomos (2, 10, 14 e 20). As amostras com presença de Chromothripsis tiveram uma media de 468 CNVs/amostra, enquanto o grupo sem o fenômeno teve uma média de 255 CNVs/amostra. Após essa avaliação de CNVs, comparamos os níveis de expressão de RNA entre duas amostras com a presença e quatro tumores com ausência de Chromothripsis. Cerca de 171 genes estão presentes em regiões de CNVs diferentes entre os grupos avaliados. Destes, a maioria (77 genes) são relacionados com funções de comunicação celular e ao ciclo celular. Um grupo de 43 genes foi relacionado às vias de processo metabólico (principalmente associado ao metabolismo do RNA) e 27 genes associados à organização do componente celular ou biogênese. Tumores com Chromothripsis possuiam 4 genes do sistema imune menos expressos (CADM1; CLEC4A; CCR1; CD164) e 12 estavam superexpressos (IL32, LAT, BCL3, FCAR, RFX1, ILIB, CXCL1, SPON2, CCR6, IL6, SEMA3C, GEM). Os genes pouco expressos também têm um papel na via de adesão celular. A adesão celular está associada à progressão do câncer e metástase. Em seguida, re-analisamos as CNVs de 82 amostras de OS e 35 linhagens celulares de OS, usando microarrays disponíveis em bancos de dados públicos (GEO e arrayexpress), para identificar potenciais regiões cromossômicas comumente envolvidas em alterações caóticas no número de cópias de DNA, especialmente CTLPs. Identificamos Chromothripsis em 27 amostras (11 tumores e 16 linhagens), afetando 17 cromossomos diferentes. Os cromossomos 2, 8 e 12 foram alvos frequentes de Chromothripsis em OS. Em seguida, foram analisados dados de sequenciamento WGS de 12 tumores de OS disponíveis no banco de dados online dbGaP. Fizemos a avaliação da variação de número de cópias para caracterizar detalhadamente as alterações caóticas e identificar asregiões cromossômicas alvo envolvidas nas regiões de alterações caóticas no número de cópias do DNA. Encontramos CTPLs em 7 (58%) das 12 amostras de OS analisadas, usando dados de sequenciamento total. Foram encontrados 12 cromossomos diferentes afetados pelo fenômeno de alteração caótica. CTPLs foram detectadas em 62,5% das amostras de pacientes que faleceram em decorrência deste tumor. Os cromossomos 1, 3 e 7 foram um pouco mais afetados por Chromothripsis nas amostras disponibilizadas pelo dbGaP. Além disso, os cromossomos 2 e 12 também foram afetados por Chromothripsis nessas amostras. Cerca de 700 genes/tumor foram encontrados nas regiões de CTLPs. Um total de 101 genes foram localizados em regiões de alteração de número de cópias que distinguem os grupos com e sem Chromothripsis. Estes genes estão relacionados com vias de processo celular (45 genes - os quais 17 estão associados à comunicação celular) e processo metabólico (22 genes - os quais 19 estão associados ao processo metabólico primário). Nós também comparamos os níveis de expressão gênica das amostras disponíbilizadas pelo dbGap, em que foram avaliados dados de expressão de 6 amostras de RNA de OS com Chromothripsis e de 3 amostras de RNA de OS sem Chromothripsis . Diferentes algoritmos e ferramentas foram utilizadas para avaliação de RNA. Nós analisamos os dados de expressão por dois diferentes mecanismos: EdgeR e Nexus Expression. Ambos mostraram menor expressão de RNA nas vias de comunicação celular e processo metabólico primário em amostras com Chromothripsis. Os genes com regulação negativa da resposta do sistema imunológico foram encontrados em ambas ferramentas (COL8A1, CCL25). Para estudar os cromossomos envolvidos na formação de micronúcleos na linhagem celular U2OS, foram investigados erros na divisão celular induzidos por drogas (durante a anáfase). Esta etapa foi realizada durante o período de doutorado sanduíche, no Barts Cancer Institute, em Londres-UK. Os cromossomos com erros durante a anáfase foram contados por meio da técnica de FISH centromérica. Os cromossomos mais comumente encontrados com erros foram Chr2, Chr6, Chr11 e Chr12. Estes dados corroboram a ideia de que alguns cromossomos são mais suscetíveis a erros de divisão celular e colaboram para maiores índices de CTPLs em certos tumores. O fenômeno Chromothripsis parece estar presente em pelo menos 30% dos tumores de osteossarcoma e pode estar contribuindo para o fenótipo mais agressivo deste tumor ósseo. / Whole genome sequencing methods applied to a number of human cancers have detected a new class of chaotic DNA alterations in tumors called Chromothripsis. This mechanism of genomic instability is relatively common in the human bone tumor osteosarcoma (OS), but there are few studies in this tumor addressing either its causes or consequences. In this thesis we initially re-analyzed the DNA copy number data using newer software designed to detect signatures of Chromothripsis-like Patterns (CTLPs) using ten OS samples previously studied by our laboratory. We found three of the osteosarcomas had Chromothripsis signatures that affected four chromosomes (2, 10, 14 and 20). The osteosarcomas with Chromothripsis had a median of 468 copy number abnormalities per tumor compared to 255 for OS tumors without Chromothripsis. Next, we compared global RNA expression levels from two OS samples with Chromothripsis to four tumors without Chromothripsis to determine the types of gene expression differences associated with this process. We found that 171 genes mapped to regions of Chromothripsis with the majority (77 genes) mainly having functions related to cellular communication and cell cycle. There were 43 genes that were related to metabolic process (mainly associated with RNA metabolism) and 27 genes with cellular component organization or biogenesis. Also, there were four genes associated with the immune system that were underexpressed (CADM1; CLEC4A; CCR1; CD164) and 12 were overexpressed (IL32, LAT, BCL3, FCAR, RFX1, ILIB, CXCL1, SPON2, CCR6, IL6, SEMA3C, GEM) in the Chromothripsis tumors. Interestingly, all the genes underexpressed also have a role in cell adhesion pathway. Cell adhesion is associated with cancer progression and metastasis. We then reanalyzed DNA copy number data from 82 OS tumors and 35 OS cell lines using microarrays datasets available in public databanks (GEO and arrayexpress), to identify potential chromosomal regions commonly involved in chaotic DNA copy number alterations, especially CTLPs. We found Chromothripsis in 27 OS samples (11 tumors and 16 cell lines), affecting 17 different chromosomes. Chromosomes 2, 8 and 12 were frequent targets of Chromothripsis in OS. Sequentially, the DNA copy number alterations were analyzed using whole genome sequence data of 12 OS tumors available from dbGaP databank to characterize chaotic alterations in detail and identify the target chromosomal regions involved in Chromothripsis. We found Chromothripsis patterns in 7 (58%) of the 12 OS samples analyzed using whole genome sequence data. In total there were12 different chromosomes involved affecting 62.5% of samples from patients that died from OS. Chromosomes 1, 2, 3, 7 and 12 were slightly more often Chromothripsis target locations. Nearly 700 genes per tumor were found in the CTLPs regions. A total of 101 genes were located in regions of copy number change that distinguished the group of OS with Chromothripsis in comparison to OS without Chromothripsis. These genes are related with cellular process (45 genes - which 17 are associated with cell communication) and metabolic process (22 genes - which 19 are associated with primary metabolic process). We were also able to compare the RNA levels from the dbGap samples when expression data was available: comparing 6 OS RNA samples with Chromothripsis to 3 OS RNA samples without Chromothripsis. Both the EdgeR and Nexus Expression pipelines showed downregulation in cell communication pathway and primary metabolic process in samples with Chromothripsis. Genes downregulated of immune system response pathway were found in both pipeline (COL8A1, CCL25). To study the chromosomes involved in micronucleus formation in the OS cell line U2OS, errors in cell division induced by drugs during the anaphase were evaluated during the sandwich period at Barts Cancer Institute in London-UK. The lagging chromosomes were counted and the most common chromosomes with errors were Chr2, Chr6, Chr11, and Chr12. These data provide further support to the idea that some chromosomes are more susceptible to cell division errors and corroborate with the chromosomes affected by CTPLs in some tumors.

[pt] Esta tese tem por objetivo investigar numérica e experimentalmente a mecânica da formação dos aneurismas na aorta. A parte experimental foi realizada no Laboratório de Membranas e Biomembranas utilizando-se tubos cilíndricos de látex sob pressão hidrostática e tubos de silicone com geometria aproximada da aorta. Foi investigada a pressão necessária à formação dos aneurismas e o comportamento do material ensaiado. A parte numérica foi realizada por meio do método dos elementos finitos através do programa ABAQUS. Na análise numérica foi validada a análise experimental e realizados alguns estudos paramétricos. / [en] The objective of this work was to investigate numerical and experimentally the mechanics of aortic aneurisms. The experimental part was done in the Laboratory of Membranes and Biomenbranes using latex cylindrical tubes under hydrostatic pressure and rubber tubes with the approximate aortic geometry. The required pressure to formation of aneurisms was investigated as well the behavior of the material during the experiments. The numerical part was done with finite element method with the ABAQUS program. In the numerical analyses the experimental analyses was validated and some parametric studies was done.

O objetivo da presente dissertação foi avaliar e comparar o comportamento da movimentação do joelho, nos testes Drop Vertical Jump (Drop), Single Hop (Hop), Triple Hop (Triplo), Cross-over Hop (Cross), Six-Meter Timed Hop (6M) e Sidestep Cutting (Sid), através de análises cinemáticas das rotações e velocidades angulares do joelho, e pela co-ativação muscular do membro inferior, em jogadoras de handebol. O desenho experimental da pesquisa foi um estudo transversal, na qual foram avaliadas 12 participantes (idade média de 21,2±2,4 anos, massa corporal média de 68,9±10,3kg e estatura média de 1,70±0,04m). Antes das avaliações, todas foram demarcadas com 25 marcadores retrorefletivos em proeminências ósseas de interesse. Além disso, foram acoplados 10 sensores de eletromiografia (EMG) (EMG TrignoTM Wireless System), nas musculaturas do reto femoral, bíceps femoral e glúteo médio. Após foram aplicados os seis testes funcionais, em três tentativas válidas com o membro dominante. Os dados da cinemática foram obtidos pelo sistema de captura de movimento VICON (Centennial, CO, EUA) e analisados por rotinas desenvolvidas no software MatLab (Mathworks Inc., Natick, MA, USA). Os ângulos de rotação do joelho, especificamente o valgo do joelho, foram obtidos pelos Ângulos de Euler. Já as velocidades angulares escalares foram geradas pelo quatérnion unitário. E por último, as razões de co-ativação entre o reto femoral/bíceps femoral (RB) e reto femoral/glúteo médio (RG) foram através do sinal da integral normalizada da EMG. A partir disso, foram traçados os momentos das variáveis em cada teste avaliado. Para os ângulos de valgo foram extraídos os valores no contato inicial (CI), 40 e 100 ms após o CI, na flexão máxima (Flexmax) e no valgo máximo do joelho (Valgomax). Para as velocidades angulares foram os mesmos instantes, mais o momento de velocidade positiva (Velpos) e velocidade negativa (Velneg). Para as co-ativações foram os mesmos instantes dos ângulos, mais o momento da força pico de reação do solo (FPRS), por duas plataformas de força (Columbus, EUA). Nos ângulos de valgo houve interação [F(2,220)=11,456; p<0,001] na comparação (momento x testes) revelando diferenças significativas nas comparações pareadas. No CI, no 100ms e na Flexmax o Sid apresentou diferença para quase todos os outros testes, assim como o Drop na Flexmax. Nas velocidades angulares houve interação [F(30,330)=14,476; p<0,001] com diferenças significativas nas comparações pareadas. Nos instantes de 40ms, 100ms, Velpos e Velneg o Drop apresentou diferença para quase todos os testes, assim como o 6M apontou diferença para todos os outros testes no 100ms e Velneg. Houve ainda relação moderada: do Cross no momento de Valgomax nas variáveis ângulo de valgo e a velocidade angular (p=0,032); do Sid no momento 40ms nas variáveis do ângulo de valgo e a coativação RB (p=0,015); e no Hop no momento 100ms nas variáveis de ângulo de valgo e a coativação RG (p=0,029). Contudo, pode-se concluir que os testes funcionais de instabilidade dinâmica do joelho para as variáveis cinemáticas apresentam comportamentos específicos. Além disso, ficou demonstrado que o aumento do valgo do joelho no Cross é influenciado pela rapidez da velocidade angular. Podemos concluir ainda, que a adaptação neuromuscular RB, no Sid - 40ms, sofre a influência direta do ângulo de valgo, e que o sinergismo de RG, no Hop - 100ms, é fundamental para o controle do ângulo de valgo do joelho / The objective of this thesis was evaluate and compare the knee movement behavior, in the tests Drop Vertical Jump (Drop), Single Hop Test (Hop), Triple Hop Test (Triple), Cross-over Hop Test (Cross), Six-Meter Timed Hop Test (6M) e Sidestep Cutting (Sid), through rotation and knee angular speed kinematic analysis, and by the low member muscles co-activation, in female handball players. The experimental research design was a cross-sectional in which were evaluate 12 participants in the average age of 21.2±2.4, average body mass of 68.9±10.3kg and average height of 1.70±0.04m. Before the evaluation all made a 5 minutes warm-up and marked with 25 reflective markers in bony prominences of interest for further kinematic analysis. Besides that, where attached 10 electromyography sensors (EMG TrignoTM Wireless System), recto-femoral muscles, femoral biceps and gluteus medium. After the volunteer preparation where evaluated the six functional tests Drop, Hop, Triple, Cross, 6M and Sidestep Cutting in three valid attempts with the dominant limb. The kinematic data where obtained by the movement capture system VICON (Centennial, CO, EUA) and analyzed by the developed routines using the software MatLab (Mathworks Inc., Natick, MA, USA). The knee rotation angle, specifically the knee valgus, where generated by the sequences of Euler rotation angle. The scalar angular speeds where drawn by unitary quaternion. Finally, the co-activation ratios between the recto-femoral/femoral biceps (RB) and recto-femoral/gluteus medium (RG) where normalized integral sign by EMG. From this where set the variables moments in each evaluated test. To the valgus angle where extracted the initial contact values (CI) through a force platform (Columbus, EUA), 40ms and 100ms after the CI, in maximum flexion (Flexmax) and maximum knee valgus (Valgomax). To angular speeds where the same moments plus the positive speed momentum (Velpos) and negative speed momentum (Velneg). To the co-activation where used the same angle moments plus the moment of force peak ground reaction (FPRS). In the valgus angle there was interaction [F(2,220)=11,456; p<0,001] comparing (moment x tests) revealing significant differences in pairwise comparison. In CI, on 100ms and Flexmax the Sid presented difference to all most all the other tests likewise the Drop on Flexmax. In the angular speed there was the interaction [F(30,330)=14,476; p<0,001] with significant differences in pairwise comparison. In the moment 40ms, 100ms, Velpos and Velneg the Drop presented differences to all most all the other tests likewise the 6M pointed differences to all the other 100ms and Velneg tests. There was also a moderated relation from: Cross in the Valgomax moment in valgus angle variables and angle speed (p=0,032); Sid in 40ms moment the valgus angle variables and the co-activation (p=0,015); Hop in 100ms moment the valgus angles variables and co-activation RG (p=0,029). We can conclude that the knee dynamics instability functional tests in the dynamic valgus critical moments analysis, show that the valgus angle variables and angular velocity specific behaviors in the tests applied. Besides that was established that the knee valgus increase in Cross is influenced by the speed of angular velocity. Also can be concluded that the neuromuscular adaptation RB in SID - 40ms, has a direct influence of valgus angle and the synergism of Hop - 100ms, is fundamental to the knee valgus angle control

Dostoiévski, escritor russo do século XIX, compôs uma vasta obra, na qual procurou dar voz a todos os dilemas e contrastes presentes na alma humana; e conseguiu este feito sem procurar impor suas próprias verdades, sabendo que estas, em realidade, são sempre relativas. Um dos temas mais recorrentes em sua obra é a questão da loucura e do desequilíbrio, não só de seus personagens, mas também de fatos e acontecimentos, mostrando que, muitas vezes, na loucura do caos da vida, reside uma ordem e uma lógica superiores e, portanto, incompreensíveis para a mente humana, a qual acaba por considerar estes acontecimentos como fruto da insanidade. Isto despertou nosso interesse e resolvemos dedicar nosso estudo a este inquietante tema. / Dostoyevsky, Russian writer of the 19th century, accomplished a large literary output, in which he sought to give voice to all the dilemmas and contrasts existing in the human soul, and he perpetrated this deed without attempting to impose his own truths, knowing that these, in fact, are always relative. One of the most recurrent themes in his work is the issue of madness and instability, not only of his characters, but also of facts and events, showing that, oftentimes, in the madness existing in the chaos of life reside both a superior order and a superior logic and, therefore, incomprehensible to the human mind, which ends up regarding these events as a fruit of insanity. That aroused our interest and we have decided to dedicate this study to this unsettling theme.

Este trabalho apresenta o dimensionamento de pilares, de acordo com a nova NBR 6118:2003 - Projeto de Estruturas de Concreto. É considerado o estado limite último de instabilidade, possível de ocorrer em configurações de equilíbrio de peças de concreto armado submetidas a solicitações normais. Esse estudo torna-se fundamental para que seja possível propor soluções estruturais seguras e economicamente viáveis, de modo a suprir os questionamentos que possam surgir aos projetistas de estruturas e profissionais da área, além de constituir uma bibliografia básica de consulta com relação a esse tema. O objetivo é pesquisar os itens relacionados ao dimensionamento de pilares, e investigar a validade dos processos aproximados, através de exemplos abrangendo as situações possíveis dentro do campo de aplicação proposto, de forma a criar um conteúdo de \"Prática Recomendada\", mais acessível aos profissionais da área e envolvendo critérios práticos de dimensionamento, colocando à disposição um resumo do que existe na norma e o que é importante que seja seguido. Inicialmente, mostra-se o cálculo do comprimento equivalente do pilar, enquanto elemento isolado da estrutura, e do índice de esbeltez limite, abaixo do qual os efeitos de 2ª ordem podem ser desprezados. Em seguida, os diferentes processos para determinação dos efeitos locais de segunda ordem são comparados entre si. / This work presents the computing of columns, in accordance with the new NBR 6118:2003 - Project of Structures of Concrete. It\'s considered the ultimate limit state of instability, possible to occur in equilibrium configuration of reinforced concrete columns submitted to normal loads. This study has been fundamental to make possible to propose safe and economically reasonable structural solutions, in order to supply the questionings that can appear to the designers of structures and professionals of the area, beyond to constitute a basic bibliography of consultation with regard to this subject. The objective is research details related to the columns project, and investigate the validity of the approached processes, through examples enclosing the possible situations inside the application field, to created a content of \"Recommended Practice\", more accessible to the professionals of the area and involving practice criterions of computing, placing to the disposal a summary of that exists in the norm and what is important to be followed. Initially, will be showed the calculation of the equivalent length of the column while isolated element and the limit of the index of slenderness, below of which reveals that the second order effects can be rejected. After that, the different processes for determination of the local effects of 2ª order are compared between itself.