L'objectif de ce projet est l’étude de la plasticité des circuits corticaux dans le contexte de l'apprentissage des souris « sauvages » et modèles du syndrome de l’X fragile. Des études sur l'efficacité de la combinaison d'enregistrement des potentiels de champ locaux extracellulaires avec la stimulation laser UV (LSPS) pour cartographier les réseaux ont été réalisées. Nous avons trouvé des enregistrements de champs extracellulaires qui pourraient être utilisés pour détecter les réponses synaptiques évoquées par LSPS. Nos résultats indiquent une méthode alternative pour obtenir des cartes complètes de réseaux intracorticaux excitateurs. Ensuite, nous avons développé un paradigme d'apprentissage associatif sensoriel et étudié ses effets sur les réseaux intracorticaux excitateurs du cortex baril. Ex vivo un affaiblissement des projections excitatrices entre les couches 4 et 2/3 qui dans les colonnes de vibrisses C a été observée. Enfin, nous avons utilisé ces mêmes approches dans une souris modèle du syndrome de l'X fragile (FXS). Pour étudier les liens entre les déficits sensoriels, l'apprentissage associatif et les altérations fonctionnelles des réseaux sensoriels, nous avons utilisé un modèle de souris mutantes dans lequel la pathologie FXS était ciblée sur la couche 4 du cortex somatosensoriel. Il a été constaté que les souris WT présentaient une dépression similaire, alors qu'elle était absente FXS. En conclusion, les études sur les mutants sensoriels de type sauvage ont mis en lumière les conséquences de l'apprentissage sur les réseaux corticaux sensoriels et les liens entre la plasticité des réseaux corticaux sensoriels et les capacités cognitives. / The aim of this project is to study the plasticity of the cortical circuits in the context of the learning of wild type mice and models of Fragile X Syndrome. First, investigations into the efficacy of recording combination of extracellular local field potentials with UV laser stimulation (LSPS) to map networks were performed. We found extracellular field records could be used to detect the synaptic responses evoked by LSPS. Our results indicate an alternative method for obtaining complete maps of excitatory intracortical networks. Next, we developed a sensory associative learning paradigm and studied its effects on excitatory intracortical networks the barrel cortex. Ex vivo a weakening of the excitatory projections between layers 4 and 2/3 which in the columns of vibrissae C was observed and declined function of the speed of the behavioural response. Finally, we used these same approaches in a Fragile X Syndrome (FXS) model mouse. To study the links between sensory deficits, associative learning, and functional alterations of sensory networks, we used a model of mutant mice in which the FXS pathology was targeted to the layer 4 of the somatosensory cortex. Our hypotheses were that behavioural conditioning would change the cortical sensory circuits of the FXS sensory mutant and that the abnormal plasticity of these circuits would in turn affect the performance. It was found the WT mice exhibited a similar depression, whereas it was absent FXS. In conclusion, wild type mouse and FXS sensory mutant studies shed light on the consequences of learning on sensory cortical networks and on the links between plasticity of sensory cortical networks and cognitive abilities.

DNA damage in spermatozoa is a crucial contributor to spontaneous abortion, severe genetic disease in the offspring and infertility. The chromatin of spermatozoa is highly compacted, transcriptionally and translationally silent, hence lacking DNA damage response (DDR). DDR foci follow within seconds after a DNA double strand break (DSB) and correlate to an abortive topoisomerase-IIb activity during spermiogenesis. When comparing the DSB frequencies at the two most fragile genomic loci (fragile sites FRA3B, FRA16D) in human and murine spermatozoa with lymphocytes, significantly increased DSB levels were detected in spermatozoa in both species. This corroborates that spermatozoa are more prone to DSBs than somatic cells. When comparing the DSB frequencies at FRA3B/FRA16D in spermatozoa of smokers with non-smokers, two-fold increases were found, probably caused by cigarette smoke components triggering abortive topoisomerase-IIβ activity. The phosphorylated DDR proteins H2AX and ATM were identified in human spermatozoa and murine spermatids using multicolour immunostaining with laser-scanning confocal microscopy (LSCM) and Western blots. Based on significantly increased DDR foci in spermatozoa of smoking men, but lacking DDR foci in response to in vitro challenge with H2O2, an abortive topoisomerase-IIb activity is the likely cause of DDR foci in spermatozoa. As DDR foci are susceptible to cigarette smoke, they can potentially be used as a novel biomarker. When comparing paternal spermatozoa, and lymphocytes as well as maternal and cord lymphocytes from 39 families for DSBs (via high-throughput LSCM pH2AX detection) and DNA fragmentation (Comet assay), significant increases were found in newborns of mothers exposed to environmental tobacco smoke and smoking fathers. When challenging lymphocytes and spermatozoa to different genotoxicants, significantly increased DNA damage in newborns compared to adults was found. This confirms an exceptional vulnerability in newborns, believed to cause increased susceptibly to disease in later life, including cancer.

Pour répondre à la demande croissante d’allègement des véhicules automobiles, les aciéristes développent une nouvelle gamme d’aciers à Très Haute Résistance (THR), dite de troisième génération. Cette thèse, inscrite dans le projet ANR MATETPRO « MeMnAl Steels », s’intéresse plus particulièrement à deux nouvelles familles d’aciers THR Fe-C-Mn-Al, produites par ArcelorMittal et potentielles candidates pour la caisse en blanc des futurs véhicules. Elle vise à mieux cerner les paramètres microstructuraux permettant de contrôler et optimiser le comportement à rupture de ces aciers.Pour représenter les deux familles d’aciers, deux matériaux modèles ont été élaborés par laminage puis recuit intercritique, conduisant à une microstructure duplex : austénite retenue (γr, pouvant se transformer en martensite par effet TRIP) et ferrite. La microstructure du premier acier, dite UFG, est ultrafine (grains de taille inférieure au micromètre) tandis que celle du second est bimodale, mêlant gros grains de ferrite δ et régions à grains fins de ferrite α et d’austénite retenue γr.Les propriétés mécaniques de la microstructure UFG dépendent fortement de la température de recuit, en raison des variations de stabilité de l’austénite retenue. A l’inverse, la microstructure bimodale est très robuste vis-à-vis de la température de recuit mais très sensible à la température d’essai. L’endommagement en traction et en résilience est très peu développé pour ces deux familles. Il est localisé aux interfaces ferrite-martensite (formée pendant l’essai). Le lien entre les modes de rupture et la microstructure bimodale, étudié à l’aide d’essais Charpy, a montré l’existence de deux transitions distinctes de mode de rupture : une transition entre rupture ductile à grandes cupules et clivage pour les gros grains de ferrite δ et une transition entre rupture interfaciale et rupture ductile à fines cupules pour les zones à grains fins {α + γr}. La rupture de la microstructure UFG est ductile à température ambiante et interfaciale à plus basse température. Cette microstructure UFG peut être vue comme un matériau modèle représentant les régions à grains fins {α + γr} de la microstructure bimodale.Pour les deux familles d’aciers, le comportement élastoplastique comme le comportement à rupture semblent dominés par la stabilité de l’austénite retenue. / To fulfil the increasing demand on lightweighting automotive vehicles, steelmakers are developing a third generation of Advanced High Strength Steels (AHSS). This work, part of the ANR project MATETPRO “MeMnAl Steels”, addressed two new families of third generation AHSS produced by ArcelorMittal which may be used for the body in white of upcoming cars. It aimed at improving our current understanding of the microstructural features allowing controlling and optimizing the fracture behavior of this steel family.Two model materials were manufactured by hot and cold rolling followed by intercritical annealing. The resulting, so-called duplex microstructure is a mixture of ferrite and retained austenite (γr, which can transform into martensite by TRIP effect). The microstructure of the first steel was made of ultra-fine grains (UFG) of ferrite and retained austenite (grain size below one micrometer), while the second steel possessed a bimodal microstructure made of coarse δ-ferrite grains and fine-grained regions of α-ferrite and retained austenite γr.The mechanical properties of the UFG microstructure were strongly sensitive to the annealing temperature, due to variations in the stability of retained austenite. On the contrary, the bimodal microstructure was very robust regarding the annealing temperature but very sensitive to the test temperature. For these two families, damage development is scarce and mainly located at ferrite-martensite interfaces. Charpy impact tests on steels with the bimodal microstructure showed that each microstructural region presents its own fracture mechanisms and a specific ductile-to-brittle transition. A transition from brittle cleavage to large-dimpled, ductile fracture was observed for coarse δ-ferrite grains, while fined-grained regions presented a transition from interfacial fracture to fine-dimpled, ductile fracture. Fracture of the UFG microstructure was ductile at room temperature and interfacial at lower temperatures. This UFG microstructure can be interpreted as a model material embodying the behavior of the fine-grained {α + γr} regions in the bimodal microstructure.For both two steels, the constitutive and fracture behavior seem to be dominated by the stability of retained austenite.

Made available in DSpace on 2016-04-29T13:48:38Z (GMT). No. of bitstreams: 1 Manoela Salem Miklos.pdf: 1766313 bytes, checksum: 610fc2901a62355b32e7508fdaac46e5 (MD5) Previous issue date: 2015-08-20 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / At the end of the 1990 s, researchers involved on the debate about the new wars introduced the discussion about the urban dimension of the contemporary conflicts to the International Relations discipline. Such discussion fostered new research lines, all of which share the perception that the urban dimension is critical to the understanding of the contemporary conflicts. The city is the place where transnational flows materialize both legal and illegal, formal and informal, material and immaterial, the place where the challenges of global governance become concrete. The debate about the fragility of the cities is one of the many lines of inquiry that emerge within this framework. This thesis seeks, first, to systematize the literature on the fragile cities from its origins, when it was linked it to the literature on fragile states, to the present. Then, it will demonstrate that the fragile cities are constituted as a new locus of humanitarianism through empirical evidence. The literature on the fragile cities creates new perspectives. Humanitarian aid Institutions inaugurate new practices, appropriating the literature on fragile cities / Inseridos no debate a respeito das novas guerras, pesquisadores introduziram à disciplina das Relações Internacionais, ao final dos anos 1990, a discussão a respeito da dimensão urbana dos conflitos contemporâneos. Tal discussão inaugurou linhas de pesquisa que compartilham a percepção de que reconhecer a dimensão urbana dos conflitos contemporâneos é fundamental para a compreensão dos mesmos. A cidade é o espaço onde se materializam os fluxos transnacionais legais e ilegais, formais e informais, materiais e imateriais, o espaço onde os desafios da governança global ganham concretude. Dentre as linhas de pesquisa que emergem nesse marco, está o debate a respeito da fragilidade das cidades. A presente tese busca, em primeiro lugar, sistematizar a literatura a respeito das cidades frágeis desde sua origem, vinculada à literatura a respeito dos Estados frágeis, até o presente. Em seguida, procura-se demonstrar através de evidências empíricas que as cidades frágeis constituem-se como novo locus do humanitarismo. A literatura sobre as cidades frágeis inaugura novas perspectivas. As instituições dedicadas à ajuda humanitária, uma vez que se apropriam de tal literatura, inauguram novas práticas

L'objectif de cette étude est d'aboutir à une meilleure compréhension de la fragilisation par les métaux liquides (FML) à travers l'étude des systèmes T91/Pb-Bi et 316L/Pb-Bi et notamment d'en établir les mécanismes mis en jeu lors du contact entre ces aciers sous tension et le métal liquide. Ce travail s'inscrit dans le cadre du projet MEGAPIE-TEST mis en place pour étudier la faisabilité d'une cible de spallation au plomb-bismuth liquide. L'effet de l'eutectique plomb-bismuth liquide sur le T91 et le 316L a été étudié en fonction de la température et de la vitesse de déformation, en utilisant des éprouvettes CCT adaptées à l'étude de propagation de fissures. La présence de Pb-Bi modifie le mécanisme de rupture du T91 au détriment de la germination, croissance et coalescence des cavités. La rupture procède alors par décohésion des bandes de cisaillement. L'effet fragilisant du Pb-Bi est très marqué aux très faibles vitesses de déformation. Une transition fragile-ductile se produit aux grandes vitesses de déformation (~10-5 m.s-1 à 160°C). Les propriétés mécaniques du 316L ne sont pas autant affectées par la présence de Pb-Bi, toutefois une transition réelle est observée sur les faciès de rupture, où là également il y a compétition entre l'effet fragilisant du métal liquide et la rupture ductile. Le mécanisme suggéré dans ce travail est fondé sur la localisation de la déformation en pointe de la fissure combinée au phénomène de réduction d'énergie de surface induite par adsorption de métal liquide (effet Rebinder) et ne fait intervenir aucun processus diffusionnel en particulier aux joints de grains.

Le but de la thèse est d'apprécier l'efficacité des programmes de reconstruction destinés à assurer le redressement économique de pays sortant de guerre civile depuis la fin de la Guerre froide. Du point de vue de la méthode, cette efficacité est évaluée à la fois par la pertinence du contenu et de l'organisation de ces programmes aux caractéristiques des économies post-conflictuelles, et par une évaluation de leur performance au vu d'indicateurs de redressement spécifiques à ces contextes. Les causes économiques des conflits et le fonctionnement d'une économie de guerre sont analysés dans la mesure ils conditionnent le passage à une économie de paix (chapitres 1 à 4). Une approche en termes d'économie politique (Stewart, Fitzgerald) recoupant inégalités horizontales et verticales et complétée par celle d'Amartya Sen contribue à rendre compte des spécificités de ce type de contexte que la théorie néoclassique ne permet pas d'appréhender. L'approche en termes de moyens d'existence (Chambers et Conway), de vulnérabilité due au contexte (Collinson) et d'économie institutionnelle donnent un cadre théorique cohérent pour cerner les caractéristiques économiques des sociétés post-conflictuelles (chapitres 5 à 7) et permettent d'identifier des facteurs bloquant ou de ralentissement du processus de redressement économique. L'étude de la configuration des programmes de reconstruction fait apparaître une prolifération d'acteurs aux logiques différentes, peu coordonnés et formant une administration de substitution non alignée dans un État fragile (chapitre 8). Le rapprochement entre programme et caractéristiques observées permet alors de procéder à l'évaluation de l'efficacité des programmes (chapitre 9). L'évaluation quantitative converge vers le constat d'un échec relatif, notamment du fait de leur lenteur (d'où risque de résurgence du conflit). Une modélisation à partir des données disponibles appuie l'identification effectuée de l'importance de certaines variables spécifiques (retour des populations déplacées, institutions, sécurité). L'analyse qualitative des causes de cette inefficacité fait apparaître : - les effets pervers du manque de coordination, analysée ici à la lumière de la théorie des coûts de transaction, de la théorie contingente et de l'analyse marginaliste, notamment sur le marché du travail et les capacités administratives, ce qui permet de mettre à jour le concept de seuil de capacités institutionnelles ; - l'inadaptation dans la conception et la mise en œuvre des programmes aux spécificités observées. Entre la référence mythifiée au Plan Marshall et l'absence d'intervention extérieure qui mènerait à un état de suffocation économique, l'analyse de cette inefficacité relative débouche sur quelques préconisations adaptables selon les contextes. / The effectiveness of reconstruction programs in post-conflict contexts Abstract The thesis aims at assessing the effectiveness of reconstruction programs intended to ensure for the economic recovery of countries emerging from civil war since the end of the Cold War. From the standpoint of the method used, this effectiveness is both evaluated through the relevance of the content and the organization of these programs with regard to the characteristics of the post-conflict economies, and through an assessment of their performances according to recovery indicators which are specific to this context. The economic causes of conflicts and the functioning of a wartime economy are analyzed because they influence the transition to an economy in the context of peace (chapters 1 to 4). An approach in terms of political economy (Stewart, Fitzgerald) comparing both horizontal and vertical inequalities and completed by Amartya Sen's approach contributes to the account of the specific characteristics of this type of context which the neoclassical theory is not enabled to grasp. The approach in terms of sustainable livelihoods (Chambers and Conways), of the vulnerability due to the context and of the institutional economy, provides a coherent theoretical framework in order to identify the economic features of post-conflict societies (chapters 5 to 7) and enables for the identification of the factors which block or slow down the process of economic recovery. The study of the configuration of reconstruction programs reveals the multiplication of actors which have different approaches, a lack of coordination in their work, and the formation of a substitute administration non-aligned to the fragile state (chapter 8). Closer ties between the programs and the observed characteristics enable for the evaluation of their effectiveness (chapter 9). The quantitative evaluation arrives at the conclusion that these programs are relative failures, especially due to their sluggishness. From the data available, the significance of some specific variables is observed (the return of populations, institutions, security). The qualitative analysis of the causes of this ineffectiveness reveals: Perverse effects due to the lack of coordination, analyzed through the transaction costs theory, the contingence theory, and the marginalist theory, more particularly in the labor markets, the administrative capacity, reveals a threshold of institutional capacities; Poor adaptation in the design and the implementation of the programs to the observed characteristics. Between the references towards the Marshall Plan and the absence of any exterior intervention, the analysis of this ineffectiveness concludes that some requirements should be adapted for each context.

Made available in DSpace on 2015-03-26T13:42:26Z (GMT). No. of bitstreams: 1 texto completo.pdf: 852162 bytes, checksum: 18350a1fa68989163ff6494b7784f27a (MD5) Previous issue date: 2012-07-18 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Fragile X syndrome is the most common inherited cause of intellectual disability with an estimated prevalence of 1 in 3600 males and 1 in 4000 to 6000 females, where it causes moderate to severe intellectual and social impairment together with syndromic features including large ears and head, long face and macroorchidism. It is most often is caused by expansion of a CGG trinucleotide repeat array in the 5' UT region of the FMR-1 gene at Xq27.3. This locus corresponds to a fragile site which can be observed in the metaphase chromosome following selective culture conditions. In this study we analyze two brothers with clinical indicative of fragile X syndrome. Peripheral blood lymphocytes were studied after 96 hrs culture periods at 37°C in RPMI 1640 (supplemented with 5% fetal serum bovine, 20 mM HEPES, 2mM glutamine and 1% M-PHA), LymphoGrow® and PB-MAX®. Two bottles for each medium was prepared for cultures with antagonists, and in each one 0,25 μg/mL fluorodeoxyuridine (FUdR) or 8 μg/mL methotrexate (Mtx) were added 72 hrs after the start of culture. Cultures were harvested after 95 hrs and 45 minutes using standard methods following exposure to 0,1 μg/mL colcemid for 15 minutes. Slides were stained with Giemsa 5% for fra(X) screening and G banding was employed for confirmation of the Xq27.3 fragile site. Lymphocytes growing in RPMI 1640, LymphoGrow and PB-MAX responded equivalently to the addition of antagonists. According to the F test at the level of 5% probability, there were no significant differences between the average number of metaphases in the three mediums in combination with FUdR. Similarly, in the three mediums methotrexate treatment was very toxic and resulted in insufficient number of analyzable cells. No fra(X) were detected in the cultures with this treatment. A total of 208 metaphases for brother 1 and 205 for brother 2 were scanned of which 21% and 20%, respectively, were positive for fra(X). These results of fragile X expression in brothers are in agreement with the estimate expression in affected males ranging from 10-40% and corroborate those of other studies which reported that men of the same family tend to have similar frequencies of fra(X). The procedures for induction of fragile site and cytogenetic analysis showed to be adequate in order to identify the presence of FRAXA in the analyzed brothers with clinical suspicion of fragile X syndrome. / A Síndrome do X frágil é a principal causa de retardo mental hereditário com prevalência estimada de 1 em cada 3600 homens e 1 em cada 4000 a 6000 mulheres. Essa síndrome provoca comprometimento intelectual e social moderado a severo, associado com características como cabeça e orelhas grandes, rosto alongado e macroorquidismo. A causa mais frequente dessa desordem é a expansão do trinucleotídeo CGG localizado na região 5' UT do gene FMR-1, em Xq27.3. Esse loco corresponde a um sítio frágil que pode ser visualizado em cromossomos metafásicos sob condições seletivas de cultura. Neste estudo analisamos dois irmãos com indicativo clínico da Síndrome do X frágil. Linfócitos oriundos de sangue periférico foram avaliados após 96 h de cultura a 37°C em meio RPMI 1640 (suplementado com 5% de FBS, 20 mM de HEPES, 2 mM de glutamina e 1% M-PHA), LymphoGrow® e PB-MAX®. Para as culturas com antagonista, dois tubos de cada meio disponível foram preparados, e em cada um, 0,25 μg/mL de fluorodeoxiuridina (FUdR) ou 8 μg/mL de metotrexato (Mtx) foram adicionados 72 h após o início da cultura. As culturas foram colhidas após 95 h e 45 min utilizando-se métodos de rotina, após exposição a 0,1 μg/mL de colcemide durante 15 min. As lâminas foram coradas com Giemsa 5% para rastreamento de cromossomos fra(X), e a técnica de bandeamento G foi empregada para a confirmação do sítio frágil na região Xq27.3. Os linfócitos cultivados nos meios RPMI 1640, LymphoGrow e PB-MAX responderam de forma equivalente à adição dos antagonistas. Não houve diferença significativa pelo teste F a 5% de probabilidade entre o número médio de metáfases observado nos três meios em combinação com FUdR. Do mesmo modo, nos três meios o tratamento com metotrexato foi muito tóxico e resultou em número insuficiente de células analisáveis. Nessas culturas com Mtx não foram detectados cromossomos fra(X). Um total de 208 metáfases para irmão 1 e 205 para o irmão 2 foram analisadas, das quais 21% e 20%, respectivamente, foram positivas para X frágil. Esses dados estão de acordo com a estimativa de expressão em homens afetados que varia de 10-40% e corroboram com os de outros estudos que reportaram que homens da mesma família tendem a apresentar frequências similares de fra(X). Os procedimentos para a indução de sítio frágil e análise citogenética mostraram-se adequados para identificação de FRAXA nos irmãos analisados com indicativo clínico da Síndrome do X frágil.

La bonne ténacité des aciers pour gazoducs aux basses températures est nécessaire pour éviter la propagation de fissures de manière catastrophique. Cette étude vise à améliorer la compréhension physique et l'évaluation quantitative du comportement à rupture des aciers pour gazoducs laminés à chaud, en nous intéressant plus particulièrement aux températures au pied de la transition ductile-fragile .La résilience de ces aciers est généralement validée à l'aide d'essais dits drop weight tear tests (DWTT), après lesquels le faciès de rupture doit contenir moins de 15% de zone fragile. Pour les aciers mis en forme par laminage thermomécanique (TMCP), des ruptures fragiles hors plan, comme le délaminage (qui se propage dans le plan de laminage de la tôle), et la rupture fragile en biseau le long des plans dits thêta (inclinés de 40° autour de la direction de laminage par rapport au plan de laminage) apparaissent dans la transition ductile-fragile. Ces modes de rupture, observés lors des essais de résilience (DWTT, Charpy) et de ténacité (CT), affectent la résistance à la rupture de ces aciers.L'anisotropie de l'écoulement plastique, puis celle de la sensibilité à la rupture par clivage ont été caractérisées en fonction de la température, à l'aide d'essais de traction sur des éprouvettes lisses et entaillées conçues pour cette étude. L'analyse mécanique de ces essais à l'aide de calculs par éléments finis a permis de déterminer des contraintes critiques de clivage dans les directions perpendiculaires au plan de laminage et aux plans thêta. Les valeurs obtenues dans ces directions sont de 25% inférieures à celles correspondant aux directions de laminage et travers long.L'anisotropie de la contrainte critique de clivage a été quantitativement corrélée à l'anisotropie de microtexture du matériau. Des entités appelées « facettes de clivage potentielles » ont été définies et mesurées dans cette étude, comme des régions contenant un plan {100} défavorablement orienté et dans lesquelles les fissures de clivage se propagent sans être arrêtées. Par exemple, un plan contenant 20% de facettes de clivage potentielles aurait une contrainte critique de clivage de 20% moins élevée qu'un plan présentant seulement 10% de facettes de clivage potentielles.La taille et la forme de ces facettes de clivage potentielles évoluent avec la déformation plastique. Par conséquent, la contrainte critique de clivage est affectée par l'historique de déformation. Dans le cas du délaminage, les facettes de clivage potentielles s'allongent au cours d'un chargement dans la direction travers long, conduisant à une augmentation de leur taille effective et par conséquent à une diminution (qui peut atteindre 30%) de la contrainte critique de clivage dans le plan de la tôle. Cette diminution facilite in fine l'apparition du délaminage. De plus, la présence de micro-fissures ductiles facilite la rupture par délaminage en modifiant l'état de contrainte local. Un critère a ainsi été proposé pour prédire numériquement l'amorçage du délaminage dans des éprouvettes de traction et/ou de résilience Charpy.L'application de cette approche à des échantillons traités thermiquement et à des échantillons pré-déformés a montré que la sensibilité au délaminage pouvait être contrôlée en modifiant la texture locale initiale du matériau. / High toughness of pipeline steels at low temperature is required to avoid catastrophic propagation of brittle crack. The aim of the study is to improve physical understanding and quantitative assessment of the toughness behavior of hot-rolled pipeline steels, focusing on the lower part of the ductile to brittle transition temperature range.The impact toughness of these steels is commonly validated using drop weight tear tests (DWTT), on the basis of fracture surfaces that must exhibit less than 15% of brittle fracture appearance. In thermomechanical control processed steels, brittle out-of-plane cracks such as delamination (which propagates along the rolling plane), and brittle tilted fracture (BTF) along theta-planes (tilted around RD by 40° with respect to rolling plane), have been characterized in the ductile to brittle transition temperature range, for both industrial (DWTT) and laboratory Charpy impact tests. In both cases, as well as in fracture toughness tests, such brittle out-of-plane cracking has been shown to impair the impact toughness.The anisotropy in plastic flow and sensitivity to cleavage fracture has been characterized as a function of temperature, by using tensile tests on specifically designed smooth and notched specimens. From finite element mechanical analysis of these tests, critical cleavage stresses normal to the rolling plane and the theta-plane are considerably lower (around 25%) than for planes normal to the rolling and transverse directions.The anisotropy in critical cleavage stress has been quantitatively correlated to microtexture anisotropy. So-called “potential cleavage facets” have been defined and measured in this study, as regions with unfavorably oriented {100} planes, which are taken as unit crack paths for cleavage propagation. A sample containing 20% of potential cleavage facets had a critical cleavage stress 20% lower than a sample with only 10% of potential cleavage facets.The size and shape of these potential cleavage facets evolve during plastic deformation. Therefore, the critical cleavage stress was found to be affected by plastic strain history. In the case of delamination, potential cleavage facets along the rolling plane were elongated during loading, their area was increased and the corresponding critical cleavage stress decreased by around 30% with respect to the undeformed case. This made delamination cracking easier. Moreover, the presence of a ductile crack at the initiation site of delamination locally modified the stress state and also facilitated delamination occurrence. A criterion has been developed to numerically predict the onset of delamination in tensile and Charpy specimens.Application of this approach to heat-treated and to prestrained specimens eventually showed that it was possible to modify the sensitivity to delamination by strongly modifying the initial microtexture anisotropy.

Le syndrome de l’X fragile représente la première cause de déficience intellectuelle héréditaire. Ce syndrome résulte de l’absence de la protéine FMRP. FMRP est proposée réguler, sous contrôles des mGluR-I et d’autres récepteurs, l’expression de protéines importantes pour la plasticité synaptique en se fixant spécifiquement sur leur ARNm et en modulant leur traduction. Des milliers d’ARNm cibles ont déjà été proposées dans la littérature, mais très peu ont pu être validées. Par approche de pontage covalent aux UV et immunoprecipitation (CLIP) couplé à une analyse microarray, nous avons identifié un ARNm comme cible unique de FMRP dans les neurones corticaux. Cet ARNm code pour une kinase contrôlant le niveau de deux seconds messagers lipidiques importants pour le remodelage des épines dendritiques. De plus, nous avons montré que l’activation mGluR-I dépendante de la kinase est absente dans les neurones Fmr1 KO, avec pour conséquence une altération de plusieurs espèces lipidiques du neurone. Ces défauts peuvent expliquer les altérations morphologiques et fonctionnelles des épines dendritiques, cause principale proposée du syndrome de l’X fragile. / Fragile X syndrome is the leading cause of inherited intellectual disability and is due to the absence of the RNA binding protein FMRP (Fragile X Mental Retardation Protein). FMRP is proposed to bind and regulate synaptic expression of mRNA targets upon mGluR-I activation. Thousands of mRNA targets have already been proposed in the literature, but only a few have been validated leaving unsolved the question of the genes mostly affected by the absence of FMRP in the brain of fragile Xpatients. The main project of the thesis was to identify the mRNAs associated with FMRP in cortical neurons by performing cross-linking immunoprecipitation approach (CLIP). We found that FMRP principally targets one unique mRNA which encodes an important synaptic kinase. This enzyme controls the level of two second lipid messengers important for remodeling of dendritic spines. Consequently, the mGluR-I-dependant activation of the enzyme is lost in absence of FMRP, leading to several lipid species alterations in the neuron. These defects may explain the morphological and functional alterations of dendritic spines, the hallmark of fragile X syndrome.

This thesis examines the novels Die Entdeckung der Currywurst, written by the German author Uwe Timm in 1993 and Der Vorleser, written by the German author Bernhard Schlink in 1995. In each story the main protagonist is a woman. Incorporating the ideas of the feminist movement, the thesis focuses on the notion that the literary role of women does not coincide with realistic representations of women rather it derives from traditionally stereotypical images of a femme fatale or a femme fragile. The goal is to analyse the depiction of women as literary protagonists in both novels. Do they truly comply with the traditional images of feminism or are there certain traits that deviate?