The performance of the Integrated Urban Wastewater Systems (IUWS) including: sewer system, WWTP and river, in both operational control and design, under unavoidable future climate change and urbanisation is a concern for water engineers which still needs to be improved. Additionally, with regard to the recent attention around the world to the environment, the quality of water, as the main component of that, has received significant attention as it can have impacts on health of human life, aquatic life and so on. Hence, the necessity of improving systems performance under the future changes to maintain the quality of water is observed. The research presented in this thesis describes the development of risk-based and non-risk-based models to improve the operational control and design of the IUWS under future climate change and urbanisation aiming to maintain the quality of water in recipients. In this thesis, impacts of climate change and urbanisation on the IUWS performance in terms of the receiving water quality was investigated. In the line with this, different indicators of climate change and urbanisation were selected for evaluation. Also the performance of the IUWS under future climate change and urbanisation was improved by development of a novel non-risk-based operational control and design models aiming to maintain the quality of water in the river to meet the water quality standards in the recipient. This is initiated by applying a scenario-based approach to describe the possible features of future climate change and /or urbanisation. Additionally the performance of the IUWS under future climate change and urbanisation was improved by development of a novel risk-based operational control and design models to reduce the risk of water quality failures to maintain the health of aquatic life. This is initiated by considering the uncertainties involved with the urbanisation parameters considered. The risk concept is applied to estimate the risk of water quality breaches for the aquatic life. Also due to the complexity and time-demanding nature of the IUWS simulation models (which are called about the optimisation process), there is the concern about excessive running times in this study. The novel “MOGA-ANNβ” algorithm was developed for the optimisation process throughout the thesis to speed it up while preserving the accuracy. The meta-model developed was tested and its performance was evaluated. In this study, the results obtained from the impact analysis of the future climate change and urbanisation (on the performance of the IUWS) showed that the future conditions have potential to influence the performance of the IUWS in both quality and quantity of water. In line with this, selecting proper future conditions’ parameters is important for the system impact analysis. Also the observations demonstrated that the system improvement is required under future conditions. In line with this, the results showed that both risk-based and non-risk-based operational control optimisation of the IUWS in isolation is not good enough to cope with the future conditions and therefore the IUWS design optimisation was carried out to improve the system performance. The riskbased design improvement of the IUWS in this study showed a better potential than the non-risk-based design improvement to meet all the water quality criteria considered in this study.

Le stade pre-B représente un point de contrôle crucial du développement des lymphocytes B dans la moelle osseuse. A ce stade, il y aura formation d'un récepteur intermédiaire nommé pre-BCR. Le pre-BCR est constitué de deux chaines lourdes Igµ et de deux pseudo-chaines légères (SLCs). Chaque SLC est constituée des protéines λ5 et VpreB, qui possèdent des régions « uniques » à leur extrémité N et C-terminale, respectivement. Ces régions uniques sont cruciales pour les fonctions du récepteur. La première partie de mes travaux sur l'étude du domaine λ5-UR nous a permis de proposer un modèle original d'assemblage du pre-BCR et d'apporter les bases structurales du rôle de chaperonne intramoléculaire de λ5-UR. L'activation du récepteur est permis par la formation d'une synapse immunologique. Des interactions entre la galectine-1 et λ5-UR vont permettre la formation d'un treillis d'interactions. L'étude structurale du complexe GAL1/λ5-UR, réalisée dans la seconde partie de ma thèse, a permis de déterminer la structure du complexe. L'interaction GAL1/λ5-UR engendre une modification d'affinité de GAL1 pour le lactose. Ce résultat suggère que l'interaction entre le pre-BCR et la galectine-1 peut influencer l'équilibre des interactions au niveau de la lattice en modulant l'affinité de la galectine-1 pour certains glycans. Dans la troisième partie de mon travail de thèse, des approches de glycomique fonctionnelle et structurale nous a permis l'élaboration d'un mécanisme de formation-dissolution de la synapse pre-B basés sur une modification d'affinité de GAL1 pour certains carbohydrates en présence de λ5-UR. / The pre-B stage represents a critical checkpoint in the development of B cells in the bone marrow. At this stage , there will be formation of a receptor intermediate called pre-BCR . The pre -BCR is composed of two heavy chains Igμ and two surrogate light chains ( SLCs ) . Each SLC consists of two proteins: λ5 and VpreB , which have "unique region" to their N-terminus and C -terminus, respectively. These unique regions are crucial for the functions of the receptor. The first part of my work on the domain λ5-UR has allowed us to propose an original model for assembling the pre -BCR and provide the structural basis of the role of intramolecular chaperone of λ5-UR. Receptor activation is allowed by the formation of an immunological synapse. Interactions between galectin-1 and λ5-UR will allow the formation of a lattice interactions. The structural study of complex GAL1/λ5-UR , conducted in the second part of my thesis, has allowed to determine the structure of the complex. These interactions GAL1/λ5-UR generate a modification of affinity of GAL1 for lactose. This result suggests that the interaction between the pre-BCR and galectin-1 may affect the balance of interactions at the lattice by modulating the affinity for galectin-1 for some glycans. In the third part of my thesis, approaches to structural and functional glycomics has allowed us to develop a mechanism of formation-dissolution of the synapse pre-B based on a modified affinity of GAL1 for certain carbohydrates in presence of λ5-UR.

<div>The numerical calculation of the electromagnetic fields within electric machines is sensitive to the magnetic characteristic of steel. However, the magnetic characteristic of steel is uncertain due to fluctuations in alloy composition, possible contamination, and other manufacturing process variations including punching. Previous attempts to quantify magnetic uncertainty due to punching are based on parametric analytical models of <i>B-H</i> curves, where the uncertainty is reflected by model parameters. In this work, we set forth a data-driven approach for quantifying the uncertainty due to punching in <i>B-H</i> curves. In addition to the magnetic characteristics of steel lamination, the remanent flux density (<i>B_r</i>) exhibited by the permanent magnets in a permanent magnet synchronous machine (PMSM) is also uncertain due to unpredictable variations in the manufacturing process. Previous studies consider the impact of uncertainties in <i>B-H</i> curves and <i>B_r</i> of the permanent magnets on the average torque, cogging torque, torque ripple and losses of a PMSM. However, studies pertaining to the impact of these uncertainties on the combined machine/drive system of a PMSM is scarce in the literature. Hence, the objective of this work is to study the effect of <i>B-H</i> and <i>B_r</i> uncertainties on the performance of a PMSM machine/drive system using a validated finite element simulator. </div><div>Our approach is as follows. First, we use principal component analysis to build a reduced-order stochastic model of <i>B-H</i> curves from a synthetic dataset containing <i>B-H</i> curves affected by punching. Second, we model the the uncertainty in <i>B_r</i> and other uncertainties in <i>B-H</i> characteristics e.g., due to unknown state of the material composition and unavailability of accurate data in deep saturation region. Third, to overcome the computational limitations of the finite element simulator, we replace it with surrogate models based on Gaussian process regression. Fourth, we perform propagation studies to assess the effect of <i>B-H</i> and <i>B_r</i> uncertainties on the average torque, torque ripple and the PMSM machine/drive system using the constructed surrogate models.</div>

É indiscutível os inúmeros benefícios decorrentes do avanço da ciência, principalmente no campo da reprodução artificial, entretanto cada vez mais se mostra necessário impor limites, tanto na área médica quanto na jurídica, devendo-se regulamentar, legal e especificamente a matéria, com o fim de se coibir abusos e proteger direitos. Ademais, o avanço rápido da ciência tem preocupado sobremaneira a sociedade relativamente às conseqüências decorrentes do uso indevido por parte de pesquisadores, médicos e clínicas reprodutivas, das inovações e possibilidades nesta área. Nada justifica que a busca científica desenfreada, por exemplo, de seres humanos geneticamente melhorados, ultrapasse limites éticos, morais e sociais, discriminando-se àqueles que não se enquadram nos padrões sociais previamente estereotipados. Na presente pesquisa, a responsabilidade civil e penal é tratada como forma inibidora de tais atos, mas não se mostra como única solução possível. Sendo assim, questões como o direito dos embriões, o direito a vida, a dignidade humana, a sucessão hereditária, a filiação, entre outros, são objeto primordial da presente obra, de forma que lhe sejam assegurados ampla tutela jurídica nesse sentido. Também questões relativas à gestação de substituição e a autorização daqueles que pretendem implantar um embrião, sejam pais genéticos ou não, na utilização das técnicas de reprodução artificial, aqui se encontram abordadas. Busca-se também proteger o direito de igualdade entre filhos, proibindo-se consequentemente a discriminação entre eles em razão de sua origem. São também esclarecidas as técnicas de reprodução artificial, bem como as teorias relativas ao início da vida para caracterizar-se a personalidade jurídica. Por fim, há ainda, nesta obra, preocupação em esclarecer conceitos, diferenciando-se terminologias e estabelecendo-se definições necessárias tanto na área jurídica quanto médica. / It is undiscuss the numerous benefits resulting from Science advance, especially concerning artificial reproduction, however it is necessary put on limits in medical and legal concernes, having to regulatory, legal rules in order to cohabit abuses and protect rights. Moreover, fast science advance has been worring the society about consequences becomes from the improper use from reserarchers, medical and reproductive clinics concerning innovations and possibilities in this area. Nothing can justifies the fast serch, for example, for humans genetically improveds, it exceeds ethical, moral and social limits, broking down who is not in conform to social standar previously sterotyped. In this research, the civil and penal liability is treated as inhibitory form of such acts, but not appears as the only possible solution. In order, issues concerning embryos rights, such as life rights, human dignity, hereditary succession, among others, are primary subject of this book, performing ensured broad legal protection accordingly. Also issues related to surrogate mother and the authorization of those intending to deploy an embryo, be or not the genetic fathers, in the use of artificial reproduction technical, here related in this work. Also seeks proteting to the rights of equality between sons, in order to forbid discrimination among them because of their origins. The work also clarified the techniques of artificial reproductions, as well as theories concerning the beginning of life to be characterized legal personality. Finally, in this current work, there is worry to clarify the concepts, differing terminologies and definitions needed both in legal and medical fields.

Notre recherche se porte sur l’éthique des techniques de procédures de maternité de substitution. Nos études se basent sur la Théorie Fonctionnelle de l’Intégration et de l’information de N.H Anderson (1981). Pour l’étude menée en France auprès d’un public dit tout-venant : 236 personnes dont 62 hommes et 174 femmes ont émis un jugement de non acceptabilité concernant les procédures de maternité de substitution dans 54 scénarios construits par la combinaison de quatre facteurs : « Origine de l’embryon », «Autonomie de la mère porteuse», « Famille de la mère porteuse » et « Niveau de rémunération ». En ce qui concerne l’étude menée en Inde, c’est 430 étudiants, 275 femmes et 155 hommes, qui ont également émis un jugement de non acceptabilité pour ces mêmes 54 scénarios. Les résultats ont mis en évidence l’émergence de différents groupes de politique de jugement pour les deux études. En France, on distingue 4 clusters différents. Bien que ces clusters diffèrent dans leur jugement, on retrouve un consensus concernant le facteur « Autonomie » pour chaque groupe. Enfin, plus de 50% de notre échantillon se montre non favorable face à de telles procédures. Pour l’étude menée auprès d’étudiant indien, quatre clusters différents ont également été mis en évidence. Près d’un quart de notre échantillon n’a pas souhaité se positionner et plus de 50% des participants se montrent enclin à accepter ce type de procédures en fonction des différentes circonstances qui définissent la situation. Le jugement de non acceptabilité des procédures de maternité de substitution est influencé par les facteurs proposés et on constate l’émergence de différentes positions face à ces questionnements éthiques. / Our research deals with ethical questions about surrogate motherhood. Both of our studies are based on the Integration Information Theory of N.H. Anderson (1981). The first one took place in France with general public: 236 people of whom 62 men and 174 women. They judged the non acceptability of surrogacy on 54 scenarios combining four factors: “Type of surrogacy », « Surrogate mother’s level of autonomy », « Surrogate mother’s family situation » and «Level of Compensation ».The second study took place in India with 430 students, 275 of whom were women and 155 were men. Indian students judged the non acceptability of surrogacy on the same 54 scenarios. Further to the results different groups of judgment politics emerged for both studies. In France, four groups of participants distinguish. Even if these groups put forward different judgements, the factor « Autonomy » obtained general consensus. Finally, 50% of our French sample doesn’t agree with the surrogate motherhood procedure. In the second study, also four groups of participants distinguish. Almost 25% of the sample does not give a judgment about surrogacy and more than 50% agrees with the surrogate motherhood procedure depending on different circumstances defining the situation. The judgment of non acceptability is influenced by the factors presented and the emergence of different positions among the participants is noted.

Le travail présenté vise à mettre en place une méthodologie pour le suivi en service de la fatigue mécanique pour l’ombilical dynamique d’un système EMR flottant. L’approche envisagée consiste à simuler à l’aide d’outils numériques la réponse de l’ombilical aux cas de chargement observés sur site. Le post-traitement des résultats de ces simulations devant permettre d’accéder à différentes quantités d’intérêt en tout point du câble. Pour quantifier et réduire l’incertitude sur la réponse calculée de l’ombilical ce dernier doit être instrumenté. Un certain nombre de paramètres du modèle numérique feront alors l’objet d’une calibration régulière pour suivre l’évolution des caractéristiques de l’ombilical susceptibles d’évoluer. Dans ce contexte ce manuscrit présente et compare différentes méthodes pour analyser la sensibilité de la réponse de l’ombilical aux paramètres susceptibles d’être suivis. L’objectif est notamment d’orienter le choix des mesures à mettre en oeuvre. L’analyse en composantes principales permet pour cela d’identifier les principaux modes de variation de la réponse de l’ombilical en réponse aux variations des paramètres étudiés. Différentes approches sont également envisagées pour la calibration des paramètres suivis,avec en particulier le souci de quantifier l’incertitude restante sur le dommage. Les méthodes envisagées sont coûteuses en nombre d’évaluations du modèle numérique et ce dernier est relativement long à évaluer. L’emploi de méta-modèles en substitution des simulations numériques apparait donc nécessaire, et là encore différentes options sont considérées. La méthodologie proposée est appliquée à une configuration simplifiée d’ombilical dans des conditions inspirées du projet FLOATGEN. / The present work introduces a methodology to monitor fatigue damage of the dynamic power cable of a floating wind turbine. The suggested approach consists in using numerical simulations to compute the power cable response at the sea states observed on site. The quantities of interest are then obtained in any location along the cable length through the post-treatment of the simulations results. The cable has to be instrumented to quantify and to reduce the uncertainties on the calculated response of the power cable. Indeed some parameters of the numerical model should be calibrated on a regular basis in order to monitor the evolution of the cable properties that might change over time. In this context, this manuscript describes and compares various approaches to analyze the sensitivity of the power cable response to the variations of the parameters to be monitored. The purpose is to provide guidance in the choice of the instrumentation for the cable. Principal components analysis allows identifying the main modes of power cable response variations when the studied parameters are varied. Various methods are also assessed for the calibration of the monitored cable parameters. Special care is given to the quantification of the remaining uncertainty on the fatigue damage. The considered approaches are expensive to apply as they require a large number of model evaluations and as the numerical simulations durations are quite long. Surrogate models are thus employed to replace the numerical model and again different options are considered. The proposed methodology is applied to a simplified configuration which is inspired by the FLOATGEN project.

Multidisciplinary design optimization (MDO) refers to the process of designing systems characterized by the interaction of multiple interconnected disciplines. High-fidelity MDO usually requires large computational resources due to the computational cost of achieving multidisciplinary consistent solutions by coupling high-fidelity physics-based solvers. Gradient-based minimization algorithms are generally applied to find local minima, due to their efficiency in solving problems with a large number of design variables. This represents a limitation to performing global MDO and integrating black-box type analysis tools, usually not providing gradient information. The latter issues generally inhibit a wide use of MDO in complex industrial applications. An architecture named multi-criterion adaptive sampling MDO (MCAS-MDO) is presented in the current research for complex simulation-based applications. This research aims at building a global derivative-free optimization tool able to employ high-fidelity/expensive black-box solvers for the analysis of the disciplines. MCAS-MDO is a surrogate-based architecture featuring a variable level of coupling among the disciplines and is driven by a multi-criterion adaptive sampling (MCAS) assessing coupling and sampling uncertainties. MCAS uses the dynamic radial basis function surrogate model to identify the optimal solution and explore the design space through parallel infill of new solutions. The MCAS-MDO is tested versus a global derivative-free multidisciplinary feasible (MDF) approach, which solves fully-coupled multidisciplinary analyses, for two analytical test problems. Evaluation metrics include number of function evaluations required to achieve the optimal solution and sample distribution. The MCAS-MDO outperforms the MDF showing a faster convergence by clustering refined function evaluations in the optimum region. The architecture is applied to a steady fluid-structure interaction (FSI) problem, namely the design of a tapered three-dimensional carbon fiber-reinforced plastic hydrofoil for minimum drag. The objective is the design of shape and composite material layout subject to hydrodynamic, structural, and geometrical constraints. Experimental data are available for the original configuration of the hydrofoil and allow validating the FSI analysis, which is performed coupling computational fluid dynamics, solving the Reynolds averaged Navier-Stokes equations, and finite elements, solving the structural equation of elastic motion. Hydrofoil forces, tip displacement, and tip twist are evaluated for several materials providing qualitative agreement with the experiments and confirming the need for the two-way versus one-way coupling approach in case of significantly compliant structures. The free-form deformation method is applied to generate shape modifications of the hydrofoil geometry. To reduce the global computational expense of the optimization, a design space assessment and dimensionality reduction based on the Karhunen–Loève expansion (KLE) is performed off-line, i.e. without the need for high-fidelity simulations. It provides with a selection of design variables for the problem at hand through basis rotation and re-parametrization. By using the KLE, an efficient design space is identified for the current problem and the number of design variables is reduced by 92%. A sensitivity analysis is performed prior to the optimization to assess the variability associated with the shape design variables and the composite material design variable, i.e. the fiber orientation. These simulations are used to initialize the surrogate model for the optimization, which is carried out for two models: one in aluminum and one in composite material. The optimized designs are assessed by comparison with the original models through evaluation of the flow field, pressure distribution on the body, and deformation under the hydrodynamic load. The drag of the aluminum and composite material hydrofoils is reduced by 4 and 11%, respectively, increasing the hydrodynamic efficiency by 4 and 7%. The optimized designs are obtained by evaluating approximately 100 designs. The quality of the results indicates that global derivative-free MDO of complex engineering applications using expensive black-box solvers can be achieved at a feasible computational cost by minimizing the design space dimensionality and performing an intelligent sampling to train the surrogate-based optimization.

Estimating the structural weight of a Hybrid Wing Body (HWB) aircraft during conceptual design has proven to be a significant challenge due to its unconventional configuration. Aircraft structural weight estimation is critical during the early phases of design because inaccurate estimations could result in costly design changes or jeopardize the mission requirements and thus degrade the concept's overall viability. The tools and methods typically employed for this task are inadequate since they are derived from historical data generated by decades of tube-and-wing style construction. In addition to the limited applicability of these empirical models, the conceptual design phase requires that any new tools and methods be flexible enough to enable design space exploration without consuming a significant amount of time and computational resources. This thesis addresses these challenges by developing a parametric and physics-based modeling and simulation (M&S) environment for the purpose of HWB structural weight estimation. The tools in the M&S environment are selected based on their ability to represent the unique HWB geometry and model the physical phenomena present in the centerbody section. The new M&S environment is used to identify key design parameters that significantly contribute to the variability of the HWB centerbody structural weight and also used to generate surrogate models. These surrogate models can augment traditional aircraft sizing routines and provide improved structural weight estimations.

This thesis consists of three chapters, covering topics in both the design and modeling aspects of computer experiments as well as their engineering applications. The first chapter systematically develops a new class of space-filling designs for computer experiments by splitting two-level factorial designs into multiple layers. The new design is easy to generate, and our numerical study shows that it can have better space-filling properties than the optimal Latin hypercube design. The second chapter proposes a novel modeling approach for approximating computationally expensive functions that are not second-order stationary. The new model is a composite of two Gaussian processes, where the first one captures the smooth global trend and the second one models local details. The new predictor also incorporates a flexible variance model, which makes it more capable of approximating surfaces with varying volatility. The third chapter is devoted to a two-stage sequential strategy which integrates analytical models with finite element simulations for a micromachining process.

Identifying and understanding the relationships between observed driving behavior over long-term periods and corresponding crash involvement rates is paramount to enhancing safety improvement programs and providing useful insights for transportation safety engineers, policy markers, insurance industries, and the public. Unlike previous data collection methods, recent advancement in mobile computing and accuracy of global positioning systems (GPS) allow researchers to monitor driving activities of large fleets of vehicles, for long-time study periods, at great detail. This study investigates the driving patterns of drivers who have and who have not experienced crashes during a 14-month study period using the longitudinally collected GPS data during a six-month Commute Atlanta study. This investigation allows an empirical investigation to assess whether drivers with recent crash experiences exhibit different driving or activity patterns (travel mileage, travel duration, speed, acceleration, speed stability duration, frequency of unfamiliar roadway activities, frequency of turn movement activities, and previous crash location exposures). This study also discusses various techniques of implementing GPS data streams in safety analyses. Finally, this study provides useful guidance for researchers who plan to evaluate the relationships between driver driving behavior and crash risk with large sample data and proposes driving behavior activity exposure metrics of individual drivers for possible safety surrogate measures as well as for driver re-training and education programs.