A vital factor for foetal development is the nutrient transport at placental level. This is because any disturbances in the maternal compartments, for example due to maternal stress or nutritional status, which will affect foetal development, will involve the foetal-placental barrier. Moreover, numerous studies have linked other factors such as preterm labour as the leading cause of perinatal morbidity and mortality in the developed world. To this date, despite a numerous epidemiological and clinical studies that identify potential risk factors for the mother as well as the foetus, there is no comprehensive analysis at all these levels taken from the same cohort of patients. Our working hypothesis is that for a successful pregnancy certain events at nutritional, biochemical, genetic and molecular level could be tightly linked. Therefore, in this study we followed a “holistic” approach investigating how maternal stress, nutrition, placental mTOR and glucocorticoid receptor (GR) signalling can influence pregnancy outcome. We have decided to map in detail the components of these two signalling pathways as they appear to cross-talk as well as been implicated in stress responses. The largest part of the questionnaire was focused on the nutritional status with questions targeting the maternal dietary habits before, as well as during, pregnancy. The collection of data took place at the Department of Obstetrics and Gynecology, University of Crete Medical School. With regards to this profile, key findings included the significant reduction in the intake of alcohol, caffeine-containing and sugar-containing refreshments, whereas passive smoking during pregnancy stayed the same. Another major finding of this part of the study was the effects of maternal stress on foetal weight and how pregnancy planning was implicated in this complex relation. In our cohort, women with negative attitudes during pregnancy gave birth to infants with significantly lower birth weights (2.5Kg) than those women showing positive or neutral attitudes towards their pregnancy (2.9Kg). We then assessed how maternal stress might affect this signalling cascade using two placental models (BeWo and JEG-3 cell lines) mimicking a stress milieu in vitro. Treatment of these cell lines with cortisol (100nM and 1000nM) significantly downregulated Deptor and upregulated GAS5 at mRNA level. In an attempt to dissect further a potential gene-environment interaction, we have assessed how 4 well-characterised polymorphisms (ThtIII 1, Bcl I, ER22/23EK, N363S) of the GR gene might affect foetal and placental weight. We have demonstrated that only the maternal ThtIII 1 polymorphism was suggestive of a nature-nurture interaction since only in ThtIII 1 II (CC), maternal stress attitude predicts foetal weight-reduction, but not in ThtIII 1 (GC) independent of confounders such as BMI, pregnancy planning or fast food eating during pregnancy. This is the first time that a gene-environment interaction between a common GR polymorphism and foetal weight was noted. Finally, one of the most important findings of our study came from the preclinical studies using placental tissues. Quantitative PCR revealed that the major transcripts in the human placenta are GRα, GAS5 (decoy for GR DNA binding) and Deptor. We have shown for first time that there are marked differences in the relative mRNA abundance of these components between term and preterm labour as well as colocalisation of GRα with GAS5. With regards to placental regulation these data conclusively demonstrate that: a) there is evidence of gene-environment interaction between maternal stress, pregnancy planning, glucocorticoid receptor polymorphisms and foetal weight and b) potential cross-talk of mTOR and glucocorticoid signalling. We propose that measuring maternal stress levels in addition to circulating cortisol and mapping for known GR polymorphisms could become a useful non-invasive tool of diagnostic and prognostic value, with implications for preterm labour.

As análises de tensões não-lineares por elementos finitos situadas no regime plástico do material demandam maior tempo de processamento computacional quando comparadas às análises lineares situadas no regime elástico. Os valores de tensões não-lineares podem ser obtidos por meio de metodologias analíticas de previsão de tensão aplicadas a componentes entalhados. Entre os métodos de obtenção de tensão em entalhes, destaca-se o método de Neuber. O presente trabalho visa avaliar a aplicação deste método aliado à análise de elementos finitos para a obtenção de tensões não-lineares em componentes automotivos fabricados em ferro fundido nodular contendo descontinuidades geométricas na superfície. Como referência foram utilizados valores de tensões obtidos através da técnica de extensometria, aplicados em dois diferentes modelos de alavancas contidas em transmissões de ônibus e caminhões. Todos os dados de entrada para os cálculos de elementos finitos foram obtidos através da caracterização do material por meio da realização de ensaios de dureza, tração e metalografia. A fim de verificar possíveis trincas ocasionadas pelos carregamentos aplicados, os componentes testados foram submetidos a ensaios de partículas magnéticas. Busca-se, assim, uma contribuição para a redução do tempo de desenvolvimento de novos produtos fabricados em componentes de ferro fundido nodular. / The analyzes of nonlinear stresses by finite elements located in the plastic regime of the material demand a longer time of computational processing when compared to the linear analyzes located in the elastic regime. The values of nonlinear stresses can be obtained by analytical methodologies of stress prediction applied to notched components. Among the methods of obtaining stresses in notches, the Neuber method is outstanding. The present work aims to evaluate the application of this method, combined with the finite element analysis to obtain nonlinear stresses in automotive components made of nodular cast iron containing geometric surface discontinuities. As reference, stress values obtained through the strain gauge technique were used, applied in two different shift levers contained in bus and truck transmissions. All input data for the finite element calculations were obtained through the characterization of the material by means of hardness, tensile and metallography tests. In order to verify possible cracks caused by the applied loads, the tested components were subjected to magnetic particle tests. Thus, a contribution is made to reduce the development time of new products manufactured in nodular cast iron components.

As análises de tensões não-lineares por elementos finitos situadas no regime plástico do material demandam maior tempo de processamento computacional quando comparadas às análises lineares situadas no regime elástico. Os valores de tensões não-lineares podem ser obtidos por meio de metodologias analíticas de previsão de tensão aplicadas a componentes entalhados. Entre os métodos de obtenção de tensão em entalhes, destaca-se o método de Neuber. O presente trabalho visa avaliar a aplicação deste método aliado à análise de elementos finitos para a obtenção de tensões não-lineares em componentes automotivos fabricados em ferro fundido nodular contendo descontinuidades geométricas na superfície. Como referência foram utilizados valores de tensões obtidos através da técnica de extensometria, aplicados em dois diferentes modelos de alavancas contidas em transmissões de ônibus e caminhões. Todos os dados de entrada para os cálculos de elementos finitos foram obtidos através da caracterização do material por meio da realização de ensaios de dureza, tração e metalografia. A fim de verificar possíveis trincas ocasionadas pelos carregamentos aplicados, os componentes testados foram submetidos a ensaios de partículas magnéticas. Busca-se, assim, uma contribuição para a redução do tempo de desenvolvimento de novos produtos fabricados em componentes de ferro fundido nodular. / The analyzes of nonlinear stresses by finite elements located in the plastic regime of the material demand a longer time of computational processing when compared to the linear analyzes located in the elastic regime. The values of nonlinear stresses can be obtained by analytical methodologies of stress prediction applied to notched components. Among the methods of obtaining stresses in notches, the Neuber method is outstanding. The present work aims to evaluate the application of this method, combined with the finite element analysis to obtain nonlinear stresses in automotive components made of nodular cast iron containing geometric surface discontinuities. As reference, stress values obtained through the strain gauge technique were used, applied in two different shift levers contained in bus and truck transmissions. All input data for the finite element calculations were obtained through the characterization of the material by means of hardness, tensile and metallography tests. In order to verify possible cracks caused by the applied loads, the tested components were subjected to magnetic particle tests. Thus, a contribution is made to reduce the development time of new products manufactured in nodular cast iron components.

Components of turbines, combustion chambers, multi-layered electronic packaging structures and nuclear reactors are subjected to transient thermal loads during their service life. In the presence of a discontinuity like crack or dislocation, the thermal load creates high temperature gradient, which in turn causes the stress intensification at the crack tips. If proper attention is not paid in the design and maintenance of components on this high stress in the vicinity of crack tips, it may lead to instability in the system and decrease in the service life. The concepts of thermal fracture mechanics and its major parameter called transient thermal stress intensity factors can greatly help in the assessment of stability and residual life prediction of such structures. The evaluation of thermal stress intensity factors becomes computationally difficult when the body constitutes of two different materials or is non-homogenous or made of composites. Fracture at bi-material interface is different from its homogenous counterpart because of mixed mode stress condition that prevails at the crack tip even when the geometry is symmetric and loading unidirectional. Because of this, the mode 1 and mode 2 stress intensity factors can not be decoupled to represent tension and shear stress fields as can be done in the case of homogeneous materials. Mathematically, the stress intensity factors at bi-material interfaces are complex due to oscillatory singularity that exists at the crack tip. Although plenty of literature is available for bi-material systems subjected to mechanical loads, very little information is available on problems related to thermal loads. Besides, problems related to transient thermal loads need special attention, since no thermal weight functions are available and the existing methods are computationally expensive. Therefore, the present investigation has been undertaken to develop computational and analytical approaches for obtaining the Mode 1 and Mode 2 stress intensity factors for bi-material interface crack problems using conservation of energy principle in conjunction with the weight function approach for various kinds of thermal loads. In the beginning of the studies, a method to extract the Mode 1 and Mode 2 stress intensity factors for bi-material interface crack subjected to mechanical load is proposed using the concept of Jk integrals. This is extended to thermal loads using J2 line integral and J2 domain integral. Furthermore, weight functions are analytically derived for thermal bi-material stress intensity factors and a computational scheme is developed. These methods are validated for several benchmark problems with known solutions.

Le laser à impulsions ultra-courtes constitue un procédé innovant et très avantageux pour la découpe de céramiques piézoélectriques PZT. Grâce à un fort confinement spatiotemporel de l’énergie au cours de l’interaction, ce système minimise les dégâts collatéraux et préserve l’intégrité physique du matériau sur des échelles micrométriques. Néanmoins, une propagation de faisceau mal maîtrisée, associée à des mécanismes d’interaction complexes fonction de la cible irradiée, peuvent impliquer de fortes disparités sur la qualité d’usinage. Dans le cadre d’une application industrielle donnée, ces travaux nous ont donc permis d’approfondir les principales étapes d’optimisation d’un tel procédé selon des critères de reproductibilité, de qualité et de rapidité. Pour cela, nous avons tout d’abord souligné l’influence des propriétés gaussiennes des faisceaux et de leur perturbation afin de définir la distribution énergétique au niveau des plans de focalisation. Aussi, la quantification de l’interaction via les critères de seuil et de taux d’ablation, d’incubation et de saturation a contribué à comprendre la réaction du matériau de manière macroscopique. Les problèmes méthodologiques inhérents à leurs calculs ont été mis en évidence et ont permis par la suite d’anticiper les formes d’usinage ainsi que les temps de procédé. Dans un second temps, l’optimisation des paramètres laser s’est appuyée sur des caractérisations aussi bien qualitatives pour l’aspect visuel que quantitatives avec l’estimation de la stoechiométrie et des contraintes résiduelles au niveau des flancs d’usinage. Nous avons en outre tiré profit de la piézoélectricité afin de développer une méthode d’observation in situ de la réponse à l’onde de choc laser contribuant à la compréhension des fissurations apparentes. Nous proposons au terme de ce travail un jeu de paramètres optimal pour la découpe de PZT assurant une bonne répétabilité du procédé tout en minimisant les défauts d’usinage comme la fissuration, les dépôts de surface et les irrégularités de bords. Des essais sur la mise en forme spatio-temporelle de faisceau sont enfin abordés principalement en tant que perspective d’accélération du procédé et encouragent son utilisation pour une future industrialisation / Lasers delivering ultrashort pulses are innovative and very attractive tools for cutting piezoelectric PZT ceramics. Thanks to an efficient spatiotemporal confinement of the energy during the interaction, these systems reduce collateral damage and preserve the physical integrity of the material on a micrometric scale. Nevertheless, uncontrolled beam propagation associated with complex interaction mechanisms depending on the irradiated target can involve large disparities on machining quality. In the context of an industrial application, this study describes the main steps of optimization of such a process according to criteria of reproducibility, quality and speed. To this purpose, we first pointed out the influence of Gaussian beam properties and their disturbance to define the energy distribution at focal planes. Thus, the quantification of the interaction with the ablation threshold, the ablation rate, incubation and saturation helped to understand the reaction of the material macroscopically. Methodological issues coming from their calculations have been highlighted while machining shapes and processing times were anticipated. Secondly, the optimization of laser parameters was based on both qualitative and quantitative characterizations. Electronic microscopy was rather used for visual appreciations whereas stoichiometry and residual stress estimations were employed to quantify the quality of side walls. We also took benefit from piezoelectricity to develop an in situ observation method which succeeded in detecting the electrical response to the laser shock wave and mainly contributed to the understanding of visible cracks. We finally propose an optimum set of parameters for cutting PZT ensuring good repeatability of the process while minimizing machining defects such as cracking, surface recast and jagged sides. Tests with spatiotemporal beam shaping were finally presented primarily as perspectives of processing time decrease so as to promote its use for future industrialization