Cette étude traite de la prise en compte du gradient de contrainte et du frottement pour calculer l’amorçage de fissures en fatigue. On s’intéresse notamment au dimensionnement d’une manille en Inconel 718 munie de bagues en Inconel 718montées avec interférence. Pour cela, on réalise des essais de fretting et de fatigue pour étudier les conditions d’amorçage de fissures en présence de gradient de contrainte et de frottement. Les résultats expérimentaux mettent en évidence l’effet du gradient des contraintes sur l’amorçage de fissures et justifient la prise en compte du gradient pour le dimensionnement en fatigue des structures. A travers ces essais balayant une gamme de gradient de contrainte étendue, on confirme que la présence d’un gradient de contrainte retarde l’amorçage de fissures. Les avantages et les inconvénients de plusieurs approches de fatigue multiaxiale intégrant le gradient de contrainte sont étudiés. De cette analyse, une proposition est faite permettant de décrire au mieux les résultats expérimentaux de fatigue et de fretting. Cette approche s’appuie sur l’utilisation d’une fonction de poids dépendant du gradient de la pression hydrostatique. Cette approche est similaire à des approches mises en oeuvre sur d’autres problématiques de fatigue ce qui permet de dégager quelques points de convergence pour traiter le problème du gradient de contrainte en fatigue. Un essai de fatigue sur une manille munie d’une bague montée avec interférence est réalisé. L’effet du gradient de contrainte sur l’amorçage de fissures dans ce système est trop faible pour que l’utilisation d’une approche intégrant l’effet de gradient soit pertinente. Cette observation est cohérente avec les résultats expérimentaux précédents obtenus dans cette étude. L’inconel 718 apparaît donc comme un matériau peu sensible à l’effet de gradient de contrainte. Une approche de fatigue multiaxiale de type Crossland permet une description raisonnable de la durée de vie du système. Une analyse numérique montre que la tenue en fatigue du système est peu sensible au coefficient de frottement alors que l’interférence a un impact beaucoup plus important. / This study focuses on the stress gradient effect and the friction to estimate the crack initiation condition in fatigue. The industrial application is a lug in Inconel 718 with shrink fitted rings also in Inconel 718.Fretting tests and fatigue tests are performed to measure crack initiation conditions with friction and stress gradient. The experimental results confirm the beneficial effect of the stress gradients on the fatigue crack initiation. These results justify the consideration of stress gradients to design structures against fatigue. Through these experiments which sweep over a large range of stress gradients, it is confirmed that stress gradient delays the crack initiation. The benefits and the drawbacks of several multiaxial fatigue approaches dealing with stress gradients are studied. Then, a proposal is done to describe accurately the experimental results of fatigue and of fretting. The proposal is based on a weight function and on the use of the gradient of hydrostatic pressure. This approach is very similar to some approaches already applied to other fatigue issues. This enables to highlight some similarities to deal with the effect of stress gradient in fatigue. Fatigue tests are finally performed on a lug with shrink fitted rings. The stress gradient effect on this application is too low to make relevant the use of a fatigue approach dealing with stress gradient. These experimental results are consistent with the previous results of fatigue and fretting. Therefore, the Inconel 718 appears as a low sensitive material to stress gradient. A multiaxial fatigue approach such the Crossland criterion enables to describe correctly the fatigue strength of this system. The numerical analysis shows that the fatigue strength of the system is not very sensitive to the coefficient of friction whereas the interference impacts significantly on the fatigue strength of the system.

Protein kinases ERK1 and ERK2 are one of the most studied proteins in cell signalling. Both proteins are involved in a plethora of processes, such as phosphorylation and activation of kinases as part of signalling pathways. Enzymes ERK1 and ERK2 are part of MAPK/ERK signalling cascade, connected to many cellular including cell proliferation, cell growth or differentiation. The MAPK/ERK signalling cascade is often activated in different types of tumors, making it a candidate for developing new chemical inhibitors. One of the important questions in fundamental research of ERK1 and ERK2 protein kinases is the search for difference between these proteins. Current knowledge points to redundancy of both proteins, howver several examples suggest otherwise. Recently, the work presented in Casanova et al. 2012 indirectly suggests divergent effect of ERK1 and ERK2 on cap-independent translation initiation. In the Laboratory of RNA biochemistry we focus on HCV IRES (Hepatitis C Virus Internal Ribosome Entry Site) dependent translation initiation. This diploma thesis lead to establish RNA interference method in our laboratory and to establish reporter system to study ERK1 and ERK2 effect on HCV IRES dependent translation initiation. Based on our data acquired during our research, we present in this work...

In eukaryotes, translation initiation is guided by up to twelve protein initiation factors (eIFs) and begins with the formation of the 43S pre-initiation complex (PIC) composed of the small ribosomal subunit (40S), eIF2.GTP/Met-tRNAi Met ternary complex, and eIFs 1, 1A, 3 and 5. The 43S PIC subsequently interacts with the 5'end of an mRNA (an mRNA recruitment step) and thus formed 48S PIC travels in 5' to 3' direction along the mRNA leader sequence to locate the AUG start codon (this presumably linear movement is generally known as scanning). Start site selection results in the dissociation of the initiation factors and joining of the large (60S) ribosomal subunit to form the 80S initiation complex poised for elongation. Eukaryotic initiation factor 3 (eIF3) plays a critical role in most of these events; however, the molecular details of most of its contributions are still unknown to us. Previous in vivo studies generated numerous mutations in all eIF3 subunits with specific defects either in the PICs assembly or in the following steps such as scanning, AUG recognition, etc. To understand the exact role of eIF3 in this intriguing process at the molecular level, we have embarked on a study that aims to dissect the individual functions of each eIF3 subunit in translation initiation using the purified...

Student Number : 9506626A - MSc (Eng) research report - School of Mining - Faculty of Engineering and the Built Environment / Significant research has been carried out over the years into what effect blast designs and techniques have on the final product in the mining process. There are numerous parameters that can be altered to deliver downstream benefits – the key is to determine which changes are appropriate for the rock body in question. A project is currently underway at Thabazimbi Iron Ore Mine (Northern Province, South Africa) to improve the operational efficiency through attention to the blasting operation. Previous research suggests changing fragmentation will have an effect on mining efficiency, but no definitive model has been developed directly linking the two. Using data collected during the project, the author developed a sensitivity analysis tool, which defines the effect of changing fragmentation on overall mine efficiency. This prediction model was based partly on theory and partly on empirical information gathered from mine databases and personnel. Over the course of this project, this model was validated through the practical implementation of the theory behind its development. This involved decreasing powder factors through increasing the drilling pattern, thus changing the resulting fragmentation of the muckpile. Subsequently, downstream effects on mining efficiency were monitored and these results were recorded in the model. The proven model was then used to identify areas of opportunity for improvement. In this report two areas are discussed, firstly, the implementation of a doped emulsion replacing ANFO across the mine, and secondly the introduction of electronic detonators. The second option would require further test work to develop confidence in the assumptions made in the model, concerning the effect of timing accuracy on fragmentation. This research report covers the background to the project, an explanation of the model and the final results obtained.

Translation initiation is a multi-step process culminating in formation of the elongation- competent 80S ribosome. It requires accurate assembly of small and large ribosomal subunits, mRNA, initiation Met-tRNAi Met and at least 12 eukaryotic initiation factors (eIFs). This phase of protein synthesis is also one of the key points of regulation of gene expression. One of the main aims of our laboratory is a complex characterization of the multiprotein eIF3 complex that has been implicated in most of the steps of translation initiation. For example, we revealed and described its novel role in translation reinitiation (REI), a gene-specific translational control mechanism that among others governs expression of an important yeast transcriptional activator GCN4. Here I present a detailed characterization of the multi-functional N-terminal domain of Tif32 (subunit eIF3a). We demonstrated that the Tif32-NTD functionally interacts with the 5' sequences of short upstream ORF (uORF1) in the GCN4 mRNA leader and thus allows efficient reinitiation downstream of this critical reinitiation-permissive uORF. Four REI- promoting elements (RPEs) were identified in the 5' sequences of uORF1, two of which were shown to work in the Tif32-NTD-dependent manner. The structure of the 5' sequences was determined...

Eventos epigenéticos como o imprinting genômico e a inativação do cromossomo X (ICX), já foram amplamente estudados em camundongos. Nesses animais muitos dos processos epigenéticos que levam à ICX já estão profundamente esclarecidos. Em humanos entretanto, o conhecimento sobre a ICX é mais limitado, em particular os eventos iniciais do processo durante o desenvolvimento embrionário. O desenvolvimento e aprimoramento de ensaios que envolvem o sequenciamento em larga escala do transcriptoma (RNA-Seq) de células únicas iniciam uma nova era nos estudos sobre a ICX. São crescentes os dados de RNA-Seq depositados em bancos de dados públicos e em 2013 os trabalhos de Xue e colaboradores e de Yan e colaboradores tornaram disponíveis os resultados de RNA-Seq de células individuais isoladas de embriões humanos a partir do estágio de duas células até a fase de blastocisto. Através de técnicas de bioinformática avaliamos o nível de expressão do gene XIST, intimamente envolvido no processo de ICX, nos diferentes estágios do desenvolvimento. Alinhamos também as leituras geradas por RNA-Seq contra o genoma humano de referência no intuito de se identificar variantes em regiões transcritas e assim verificar a origem do alelo expresso. Com isso, pudemos observar que o gene XIST tem sua expressão iniciada em embriões humanos no estágio de oito células, e que o silenciamento transcricional dos genes do cromossomo X já se iniciou no estágio de blastocisto de forma aleatória mas ainda não se disseminou, i.e. a ICX não está completa. Devido ao fenômeno de ICX, a caracterização de genes \"imprintados\" neste cromossomo é desafiadora. Ainda assim em camundongos foram relatados alguns genes do X que são assim regulados. Mulheres portadoras da síndrome de Turner (45,X) apresentam diferenças fenotípicas dependentes da origem parental do cromossomo X herdado, sugerindo a existência de genes \"imprintados\" no X humano. Em particular os genes MAOA, MAOB e USP9X foram indicados como candidatos a serem regulados por imprinting. Através do sequenciamento de regiões transcritas contendo SNPs em heterozigose foram avaliados o padrão de expressão alelo-específico dos três genes indicados. Nenhum sinal de regulação por imprinting pôde ser detectado nem em placenta nem em cérebro humano, pois a procedência dos alelos expressos era independente da origem parental. Isso não significa que a variabilidade fenotípica em mulheres com Turner não possa ser explicada por imprinting em genes do X. Experimentos de RNA-Seq em diversos tecidos humanos ou a partir de células únicas são uma abordagem conveniente para se elucidar este fenômeno / Epigenetic phenomena as genomic imprinting and X chromosome inactivation (XCI) have been widely studied in mice. While most of the processes and steps involved in XCI in mice are well studied, in humans our knowledge is still very limited, specially during early embryo development. Advances in single-cell whole transcriptome high troughput sequencing techniques (RNA-Seq) bring a new era to the XCI field. Single-cell RNA-Seq results of from 2-cell to the blastocyst stage of human embryos were published by Xue et cols and Yan et cols in 2013. Using bioinformatics techniques we searched for the XIST gene expression level (a gene closely involved in XCI) throughout the human pre-implantation embryo development. We aligned reads generated by RNA-Seq assays to the human reference genome looking for variants in gene transcriptional regions and to identify the origin of the expressed allele. Our results show that XIST expression starts from the 8-cell stage and is stabilized and upregulated at the female blastocyst stage. We also show that the transcriptional silence of X-linked genes started at the blastocyst stage and is independent of parental origin but this does not apply for all genes. We concluded that the completion of the transcriptional silence step is probably established during post-implantation stage. The search for X-linked imprinted genes is challenging due to the XCI phenomenon. Nevertheless, X-imprinted genes were reported in mice. In humans, no X-imprinted genes were found so far, but phenotypic differences reported in Turner\'s syndrome (45,X) women was related to the parental origin of the X chromosome inherited. This suggests the existence of X-linked imprinted genes, in particular MAOA, MAOB and USP9X seemed good candidates. By sequencing transcript regions containing heterozygous SNPs in these genes we could access their expression pattern. Our results show no sign of imprinting regulation of MAOA, MAOB and USP9X, neither in human brain nor in human term placenta. This does not rule out the possibility that the phenotypic differences observed in Turner\'s syndrome women could be the consequence of other unknown X-linked imprinted genes. RNA-Seq of different human female tissues is a powerful approach to finally find the genes involved in such phenotypes

Esta tese tem como foco principal a descrição e análise do ritual de iniciação pelo qual passam as moças ticuna, a chamada Festa da Moça Nova. Os Ticuna são um povo de língua isolada, habitantes, em sua maior parte, do Alto Rio Solimões (AM), distribuídos entre Brasil, Peru e Colômbia. Por ocasião da menarca, as meninas são colocadas em reclusão e é organizado o ritual. Para compreendermos esta Festa, que marca a saída das moças da reclusão, exponho suas relações com outras dimensões da vida ticuna: organização social e parentesco, mitologia, cosmologia, corpo e xamanismo. A etnografia e a análise se concentram principalmente nas canções, instrumentos musicais e narrativas míticas relacionados à Festa e seu processo ritual / This thesis mainly focuses on the description and analysis of the Moça Nova Festival, the initiation ritual through which Ticuna young women go through. The Ticuna people speak an isolated language and inhabit, for the most part, the Upper Solimões River (Amazonas, Brazil), spread across Brazil, Peru and Colombia. At the time of the menarche, girls are secluded and the ritual is organized. In order to understand this festival, which marks the moment when girls leave seclusion, I present how it relates to other dimensions of Ticuna life: social organization and kinship, mythology, cosmology, body and shamanism. Both the ethnography and the analysis concentrate primarily on the songs, musical instruments and mythic narratives related to the festival and its ritual process.

Ampliando alguns limites da escrita acadêmica para tratar do brincar na Casa de Recreação Te-Arte acolho a poética de Guimarães Rosa como suporte epistemológico e metodológico. Afirmo a filosofia trágica de Friedrich Nietzsche, a fenomenologia dos quatro elementos de Gaston Bachelard e da percepção de Maurice Merleau-Ponty. Sobretudo a sabedoria poética de Rosa e de Bachelard, sendo que Guimarães Rosa pode ser considerado também etnógrafo. Anotei o vivido no Diário de Campo significando o que estava à minha volta descobertas de crianças bem pequenas misturado aos elementos da cultura popular e à poética de Guimarães Rosa, engrandecendo este gesto ancestral o brincar. Trata-se, portanto, de uma investigação que está nas imediações da antropologia e da fenomenologia, mas que flerta com a literatura de Rosa para tratar de três núcleos do brincar: corpo, experiência e iniciação, a partir das experiências vividas na Te-Arte, um espaço de aprendizagem e uma experiência singular em educação, concebida e dirigida pela educadora Thereza Soares Pagani, a Therezita, em São Paulo. A Te-Arte existe desde 1975 e se distingue por não ter sala de aula, professores por turma e nem divisão de crianças por faixa etária. O que narro não é algo que possa ser disseminado como política pública, talvez como poética pública, como sugere Marcos Ferreira-Santos. O texto mostra os desafios de uma Pedagogia da Escolha anunciada por Rogério de Almeida e Marcos Ferreira-Santos, acolhendo outras linguagens para dialogar e deixar mostrações de uma educação de sensibilidade postulada pelos mesmos Autores. / Amplifying some limits of the academic writing to handle the aspect of recreation at Casa de Recreação Te-Arte, I make use of Guimarães Rosas poetics as an epistemological and methodological basis. I affirm the tragic philosophy of Friedrich Nietzsche, Gaston Bachelards phenomenology of the four elements and the perception of Maurice Merleau-Ponty. Especially the poetic wisdom of Rosa and Bachelard, taking in consideration that Rosa can also be considered an ethnographer. I noted the vivid in the Field Diary giving meaning to what was around me discoveries of very little children mixed with elements of popular culture and the poetics of Guimarães Rosa, exalting this ancient act recreation. Thus, this is about an investigation which is at the borders of anthropology and phenomenology, but also flirts with the literature of Guimarães Rosa, to deal with three cores of the recreation: body, experience and initiation, based on the processes experienced at Te-Arte, a place for learning and a unique educational experience, conceived and headed by the educator Thereza Soares Pagani a. k. a. Therezita, in São Paulo. Te-Arte is in activity since 1975 and is distinguished by neither having classrooms, teachers divided by groups nor divisions by age group. What I narrate is not something that can be disseminated as public politics, but maybe as public poetics, as is suggested by Marcos Ferreira-Santos. The text shows the challenges of a Pedagogy of Choice announced by Rogério de Almeida and Marcos Ferreira-Santos, bringing together other languages to form a dialogue and leave samples of an education of sensitiveness postulated by the same Authors.

The purpose of this study is to explore the meaning of womanhood in relation to the Swedish fäbod culture at the turn of the 20th century. The study is based upon a questionnaire from 1928 and the material is collected from the archives at the Nordic Museum in Stockholm and the Institute for Language and Folklore in Uppsala. Drawing upon gender and ritual theories, the study intends to gain an understanding for what it meant to be a woman of the fäbod by examining how fäbod herdswomen were culturally shaped and initiated into women both in relation to their place in the fäbod community of herdswomen, but also in respect to the wider community and society of which they were a part of.  The main conclusion of the study is that the journey into the fäbod woods can be seen as a rite of passage where adolescent girls going to the fäbod for the first time were initiated into the fäbod community of herdswomen. Womanhood is a cultural phenomenon in which women are culturally shaped and initiated into women not only by the codes, conceptions and values of the society at large, but also by the stories, customs and traditions of their local communities. The fäbod herdswomen were born into the gender power structures of a patriarchal society that sought to shape them into promising wives, and they were also women of the fäbod, initiated into the fäbod communitas, a form of female counterculture with its very own musical language, customs and traditions, and with its very own definitions of womanhood.

Orientador: Heloisa da Silva / Resumo: Elaborar compreensões sobre a mobilização de narrativas na formação de professores no âmbito do Programa Institucional de Bolsas de Iniciação à Docência (Pibid) da Universidade Federal de São Carlos, UFSCar, foi o objetivo desta pesquisa. A escolha por este espaço de formação deu-se a partir de conversas informais com uma das ex-coordenadoras institucionais e de leituras de produções vinculadas a ele e do seu regimento interno, que indicaram a obrigatoriedade do trabalho com portfólios, diários e relatórios. A metodologia esteve pautada nos pressupostos da História Oral praticada no interior do Grupo História Oral Educação Matemática, Ghoem. As compreensões elaboradas tiveram apoio no estudo de dez narrativas produzidas a partir de momentos de entrevistas com oito coordenadores de área de subprojetos e com dois coordenadores institucionais, bem como de documentos do Pibid da UFSCar. Os estudos e produções de entrevistas deram-se junto aos subprojetos da Biologia, Interdisciplinar, Letras, Pedagogia e Química, perpassando os três campi da instituição, quais sejam, Araras, São Carlos e Sorocaba. Os resultados apontam para uma pluralidade de compreensões e mobilizações das narrativas e seus usos, os quais parecem estar intimamente relacionados a aspectos da formação acadêmica, dos referenciais teóricos e do modo como o Programa é entendido por quem as mobiliza. O portfólio é instituído como o instrumento principal de formação e avaliação, embora outros instrumentos e estratégias... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: To elaborate understandings about the mobilization of narratives in the teacher’s formation in the Institutional Scholarship Program for Teaching Initiation (Pibid) of Federal University of São Carlos, UFSCar, was the objective of this research. The choice for this formation space was based on informal conversations with one of the former institutional coordinators and of readings of productions linked to it and it internal regulation, which indicated the obligation to work with portfolios, diaries and reports. The methodology assumed of the Oral History practiced inside the Group Oral History Mathematics Education, Ghoem. The elaborated understandings had support in the study of ten narratives produced from moments of interviews with eight coordinators of subprojects area and with two institutional coordinators, as well as of documents of the Pibid of UFSCar. The studies and productions of interviews took place with the subprojects of Biology, Interdisciplinary, Letters, Pedagogy and Chemistry, going through the three campuses of the institution, which are, Araras, São Carlos and Sorocaba. The results point to a plurality of understandings and mobilizations of narratives and their uses, which seem to be closely related to aspects of academic formation, of the theoretical references and how the Program is understood by those who mobilize them. The portfolio is established as the main tool for formation and evaluation, although other instruments and strategies with the narrati... (Complete abstract click electronic access below) / Doutor