Background: Effective interventions for maltreated children are impeded by gaps in our knowledge of the etiopathogenic mechanisms leading from maltreatment to mental disorders. Although some studies have already identified individual risk factors, there is a lack of large-scale multilevel research on how psychosocial, neurobiological, and genetic factors act in concert to modulate risk of internalizing psychopathology in childhood following maltreatment. To help close this gap, we aim to delineate gender-specific pathways from maltreatment to psychological disorder/resilience. To this end, we examine the interplay of specific maltreatment characteristics and psychological, endocrine, metabolomic, and (epi-)genomic stress response patterns as well as cognitive-emotional/social processes as determinants of developmental outcome. Specifically, we will explore endocrine, metabolomic, and epigenetic mechanisms leading from maltreatment to a higher risk of depression and anxiety disorders.

Research into advanced wind turbine design has shown that load alleviation strategies like bend-twist coupled blades and coned rotors could reduce costs. However these strategies are based on nonlinear aero-structural dynamics providing additional benefits to components beyond the blades. These innovations will require Multi-disciplinary Design Optimization (MDO) to realize the full benefits. This research expands the MDO capabilities of Horizontal Axis Wind Turbines. The early research explored the numerical stability properties of Blade Element Momentum (BEM) models. Then developed a provincial scale wind farm siting models to help engineers determine the optimal design parameters. The main focus of this research was to incorporate advanced analysis tools into an aero-elastic optimization framework. To adequately explore advanced designs with optimization, a new set of medium fidelity analysis tools is required. These tools need to resolve more of the physics than conventional tools like (BEM) models and linear beams, while being faster than high fidelity techniques like grid based computational fluid dynamics and shell and brick based finite element models. Nonlinear beam models based on Geometrically Exact Beam Theory (GEBT) and Variational Asymptotic Beam Section Analysis (VABS) can resolve the effects of flexible structures with anisotropic material properties. Lagrangian Vortex Dynamics (LVD) can resolve the aerodynamic effects of novel blade curvature. Initially this research focused on the structural optimization capabilities. First, it developed adjoint-based gradients for the coupled GEBT and VABS analysis. Second, it developed a composite lay-up parameterization scheme based on manufacturing processes. The most significant challenge was obtaining aero-elastic optimization solutions in the presence of erroneous gradients. The errors are due to poor convergence properties of conventional LVD. This thesis presents a new LVD formulation based on the Finite Element Method (FEM) that defines an objective convergence metric and analytic gradients. By adopting the same formulation used in structural models, this aerodynamic model can be solved simultaneously in aero-structural simulations. The FEM-based LVD model is affected by singularities, but there are strategies to overcome these problems. This research successfully demonstrates the FEM-based LVD model in aero-elastic design optimization. / Graduate / 0548 / pilot.mm@gmail.com

Αντικείμενο της εργασίας είναι η αεροδυναμική και αεροακουστική ανάλυση στροφείων ανεμοκινητήρων οριζοντίου άξονα (α-ο-α). Ο υπολογισμός του πεδίου ροής και των αεροδυναμικών συντελεστών του στροφείου ενός ανεμοκινητήρα επιτυγχάνεται κατά δύο τρόπους, με σκοπό την άμεση σύγκριση των αποτελεσμάτων με κριτήρια αφενός την ακρίβεια και αφετέρου την ευκολία ή πρακτικότητα που προσδιορίζεται κύρια σε όρους χρόνου υπολογισμού και διαθεσιμότητας υπολογιστικών πόρων. Οι δύο επιλεγμένοι τρόποι που διαφοροποιούνται στην φυσικο-μαθηματική μοντελοποίηση του προβλήματος ροής γύρω από το στροφείο του ανεμοκινητήρα, αποτελούν δύο δοκιμασμένες μεθοδολογίες ή τεχνικές ανάλυσης και σχεδιασμού περιστρεφόμενων στροφείων, τα οποία μπορούν να λειτουργούν ως κινητήριες μηχανές ή ως εργομηχανές, είναι η μέθοδος των επιφανειακών στοιχείων και η αριθμητική επίλυση των εξισώσεων Navier-Stokes. Για την αξιολόγηση των υπολογιστικών αποτελεσμάτων επιλέχθηκε ως στροφείο αναφοράς, ο πειραματικός ανεμοκινητήρας NREL phase II. Ο αλγόριθμος των επιφανειακών στοιχείων συμπλέχτηκε με ολοκληρωτικά σχήματα πρόλεξης και υπολογισμού του οριακού στρώματος με σκοπό να συμπεριληφθούν τα φαινόμενα συνεκτικότητας της ροής. Πραγματοποιήθηκε παραμετρική ανάλυση του δρομέα του ανεμοκινητήρα για διαφορετικές συνθήκες λειτουργίας του. Η σύγκριση των αποτελεσμάτων των συντελεστών πίεσης των περιστρεφόμενων πτερυγίων για τέσσερις θέσεις κατά το εκπέτασμα του πτερυγίου με τα πειραματικά δεδομένα δείχνει ικανοποιητική συμφωνία. Για την ανάλυση του πεδίου ροής που παράγεται γύρω από περιστρεφόμενους δρομείς α-ο-α χρησιμοποιήθηκε η μέθοδος της υπολογιστικής ρευστοδυναμικής (CFD). Πραγματοποιήθηκαν RANS προσομοιώσεις για διαφορετικές συνθήκες λειτουργίας του ανεμοκινητήρα και για τέσσερα διαφορετικά μοντέλα τύρβης. Το k-ω SST μοντέλο τύρβης έχει τις μικρότερες αποκλίσεις με τα πειραματικά αποτελέσματα. Η αεροακουστική ανάλυση του στροφείου ενός ανεμοκινητήρα επιτυγχάνεται με την επίλυση της ακουστικής εξίσωσης Ffowcs-Williams Hawkings, μέσω ενός υπολογιστικού κώδικα που αναπτύχθηκε γι’ αυτό το σκοπό. Από τα αποτελέσματα των προσομοιώσεων, φάνηκε στα ροδογράμματα κατευθυντικότητας του ήχου, τα επίπεδα της ακουστικής πίεσης να είναι υψηλότερα για θέσεις παρατηρητή ανάντη και κατάντη του ανεμοκινητήρα. / The aim of this study is to represent the aerodynamic and aeroacoustic analysis of horizontal axis wind turbine (ΗAWT) rotors. The calculation of the flow field and the aerodynamic coefficients over the wind turbine rotor are performed using two methodologies, the panel method and the numerical solution of Navier-Stokes equations. These two methodologies are differentiated in the mathematical modeling approach of the flow around the rotor and are utilized in the design and manufacturing phases of horizontal axis wind turbine rotors. Moreover, the results of these two methodologies are compared in terms of the accuracy and the computational time required. For the evaluation of the computational results the experimental wind turbine NREL phase II is chosen as the reference rotor. An invicid/viscous interaction algorithm is developed using integral boundary layer equations coupled with the low order panel method solution in order to account the viscous effects. A parametric analysis of the wind turbine rotor is conducted for different operating conditions. The comparison of the results of the pressure coefficients of the rotating blades for four spanwise positions along the blade with the experimental data shows satisfactory agreement. The analysis of the near and far flow field of HAWT is obtained via CFD by RANS simulations of four different turbulence models (Spalart-Allmaras, k-ε, k-ε RNG and k-ω SST). From the conducted study, it is confirmed the ability of analysis of a HAWT rotor flow field with the RANS equations and the good agreement of the computations with experimental data, when the k-ω SST turbulence model is used. The aeroacoustic analysis of the HAWT is based on the solution of the Ffowcs Williams-Hawkings (FW-H) equation via a computer code developed for this purpose. The radiation patterns of the calculated aeroacoustic noise show that high level amplitudes are calculated for upwind and downwind positions.

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L’axe hypothalamo-hypophyso-surrénalien joue un rôle essentiel dans l’adaptation et la réponse au stress. Toutefois, l’hyperactivation de cet axe ou des niveaux chroniquement élevés de glucocorticoïdes (GC) entraînent des conséquences pathologiques. Le système dopaminergique mésocortical, qui se projette dans le cortex préfrontal médian (CPFm), joue un rôle adaptatif en protégeant contre le stress. Jusqu’à présent, les interactions fonctionnelles entre les GC (ex : corticostérone) et le système dopaminergique mésocortical ne sont pas élucidées. Dans ce mémoire, nous avons évalué les effets des GC sur les fonctions dopaminergiques préfrontales en élevant chroniquement, à l’aide de minipompes osmotiques, les niveaux de corticostérone aux concentrations physiologiques maximales (1 mg/kg/h pendant 7 jours). Ce traitement n’a pas modifié significativement, chez les rats stressés ou non, les niveaux post mortem de dopamine et de son métabolite dans le tissu du CPFm. Toutefois, l’évaluation par voltamétrie in vivo des changements de dopamine extracellulaire dans le CPFmv a permis d’observer que la corticostérone augmente significativement la libération de dopamine en réponse à l’exposition à l’odeur de renard et au pincement de la queue. Nos études nous permettent de conclure que la corticostérone potentialise la fonction dopaminergique mésocorticale qui, à son tour, facilite la régulation négative en période de stress. / The hypothalamic-pituitary-adrenal axis plays an essential role in responding and adapting to stress, however overactivation of this axis or chronically high levels of glucocorticoids lead to pathological outcomes. The mesocortical dopamine (DA) system, terminating in the medial prefrontal cortex (mPFC), plays an adaptive role in protecting against stress, yet the functional interactions between glucocorticoids (eg. corticosterone) and the mesocortical DA system are not clear. In the present studies, we investigated the effects of glucocorticoids on prefrontal DA function using osmotic minipumps to chronically elevate corticosterone levels in the high physiological range (1 mg/kg/hr for 7 days). Chronic corticosterone treatment did not significantly affect post mortem levels of DA and its metabolites in PFC tissue in either unstressed or stressed rats. However, using in vivo voltammetry to monitor changes in extracellular DA release in PFC, corticosterone significantly increased DA release in response to both types of stress examined, exposure to predator odor and tail pinch stress. We conclude that corticosterone indeed potentiates mesocortical DA function, which in turn facilitates negative feedback regulation in times of stress.

The popularity of distributed generating (DG) sources have been increasing over the past few years. With the increasing penetration of these DGs, the concept of micro grid is becoming popular. A micro grid is a small power system network with distributed generating sources which can operate seamlessly irrespective of the presence of the utility grid. Operating the micro grid in this manner increases system reliability and reduces power interruptions. However, it introduces several control challenges. This thesis aims at analysing the behaviour of a micro grid system during the transition between grid connected mode and islanded mode of operation and address the control challenges through novel schemes. With the presence of grid, the micro grid system variables, such as voltage and frequency, are strictly regulated by the grid. The local sources follow the voltage and frequency reference set by the grid and supply constant power. With the loss of grid, that is when the system is islanded, the network variables need to be regulated by the local sources. The control structures for the inverter-based sources during the two operating modes are detailed in the present work. With the loss of grid, the system should be able to transfer seamlessly to islanded mode without any transients. Similarly, when the grid supply is restored, the micro grid should seamlessly resynchronize to the grid without any transients. This thesis proposes two novel controller schemes for achieving seamless transfer between grid-connected and islanded mode in micro grids. The rst scheme uses an output feedback topology to reduce the transitions during mode transfer. The second scheme uses a Linear Quadratic Regulator (LQR) theory based compensator to achieve seamless transfer. The performance of the proposed schemes have been validated through simulations on a benchmark micro grid network for various operating conditions. An experimental micro grid set-up is developed with a single inverter based DG source. The droop control scheme for islanded mode of operation has been validated on hardware.

Le syndrome d’apnées obstructives du sommeil (SAOS) est associé à une forte morbi-mortalité cardiovasculaire. L’hypoxie intermittente (HI), conséquence majeure des apnées, est à l’origine d’un stress oxydant, d’une activation de HIF-1 (hypoxia inducible factor 1) et d’une expression d’endothéline (ET-1), tous impliqués dans les complications cardiovasculaires liées à l’HI.Dans un premier temps, nous avons démontré que l’HI augmentait l’incidence des arythmies ventriculaires létales associées à l’ischémie myocardique. Parmi les mécanismes potentiels impliqués, l’analyse spectrale de la variabilité de la fréquence cardiaque et de la pression artérielle et le dosage des catécholamines ont mis en évidence une activation sympathique chez les animaux exposés à l’HI. L’HI est également à l’origine d’altérations de la repolarisation ventriculaire (allongement du QTc et du Tpeak-Tend) et d’une dispersion du gradient transmural (allongement de la durée du potentiel d’action endocardique) associées à une augmentation de l’expression de canaux calciques de type LTCC et TRPC dans l’endocarde.Dans la seconde partie de ce travail de thèse, nous nous sommes intéressés aux perturbations de l’homéostasie du zinc en réponse au stress oxydant causé par l’ischémie-reperfusion (IR) ou par l’HI et aux propriétés cardioprotectives de la supplémentation en zinc dans ce contexte. Nous avons montré que l’IR et l’HI induisaient une diminution des concentrations de zinc myocardiques et plasmatiques, respectivement. Nous avons mis en évidence les effets bénéfiques de la supplémentation en zinc vis-à-vis des arythmies ventriculaires et des altérations myocardiques induites par l’IR. L’administration de zinc lors de la reperfusion a également permis d’abolir l’augmentation de la taille d’infarctus induite par l’exposition chronique à l’HI.Finalement, nous avons étudié les effets de la déplétion en zinc sur des cellules endothéliales à l’aide d’un chélateur spécifique du zinc, le TPEN. Nous avons observé que l’exposition des cellules au TPEN entraînait une translocation nucléaire de HIF-1α et une augmentation de la sécrétion d’ET-1 avec, comme conséquence, une augmentation de la capacité migratoire des cellules endothéliales. Ainsi, une déplétion en zinc semble conduire à une activation de l’axe HIF-1-ET-1 connu pour ses effets délétères lors de l’HI.En résumé, l’exposition chronique à l’HI exacerbe les arythmies et augmente la taille d’infarctus lors de l’IR. L’activation sympathique, le stress oxydant et l’altération de l’homéostasie du zinc pourraient être impliqués. L’utilisation d’outils pharmacologiques permettrait de confirmer leur rôle et potentiellement de prévenir les altérations cardiovasculaires liées à l’HI et au SAOS. / Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Intermittent hypoxia (IH), one of the major consequences of apneas, leads to oxidative stress, activation of HIF-1 (hypoxia inducible factor 1) and endothelin (ET-1) expression, all known to play an important role in the cardiovascular consequences of OSA.First, we have demonstrated that IH increases the incidence of ischemia-related lethal ventricular arrhythmias. Among the potential mechanisms involved, spectral analysis of heart rate and blood pressure variability and catecholamine assay, showed a sympathetic activation in animals exposed to IH. IH was also responsible for alterations in ventricular repolarisation (increased QTc and Tpeak-Tend intervals) and dispersion of the transmural gradient (increased endocardial action potential duration). These alterations were associated with increased expression of endocardial LTCC and TRPC calcium channels.The second part of the thesis aimed at investigating zinc homeostasis in response to the oxidative stress induced by ischemia-reperfusion (IR) or IH as well as the beneficial effects of zinc supplementation in this context. We observed that IR and IH induced a decrease in myocardial and plasma zinc concentrations, respectively. We also highlighted the protective effects of zinc supplementation during reperfusion against the ventricular arrhythmias and myocardial dysfunction induced by IR. Zinc administration during reperfusion also abolished the increase in infarct size induced by chronic IH exposure.Finally, we investigated the effects of zinc depletion in endothelial cells exposed to TPEN, a specific zinc chelator. We observed that TPEN induced a nuclear translocation of HIF-1α and an increase in ET-1 secretion with a resulting increase in endothelial cell migration. Thus, zinc depletion appears to promote activation of the HIF-1-ET-1 axis, known for its deleterious effects upon IH.In summary, chronic IH exposure enhances ventricular arrhythmias and increases infarct size upon myocardial I/R. Sympathetic activation, oxidative stress and alterations of zinc homeostasis appear to be contributing factors. Pharmacological targeting of these alterations should be performed in order to confirm their role as well as to potentially prevent the deleterious cardiovascular consequences of IH and OSA.

Représenter un objet géométrique complexe par un ensemble de primitives simples est une tâche souvent fondamentale, que ce soit pour la reconstruction et la réparation de données, ou encore pour faciliter la visualisation ou la manipulation des données. Le choix de la ou les primitives, ainsi que celui de la méthode d'approximation, impactent fortement les propriétés de la représentation de forme qui sera obtenue.Dans cette thèse, nous utilisons les boules comme seule primitive. Nous prenons ainsi un grand soin à décrire les unions finies de boules et leur structure. Pour cela, nous nous reposons sur les faisceaux de boules. En particulier, nous aboutissons à une description valide en toute dimension, sans hypothèse de position générale. En chemin, nous obtenons également plusieurs résultats portant sur les tests d'inclusion locale et globale dans une union de boules.Nous proposons également une nouvelle méthode d'approximation par union finie de boules, l'approximation par boules à (delta,epsilon)-près. Cette approche contraint l'union de boules à couvrir un sous-ensemble de la forme d'origine (précisément, un epsilon-érodé), tout en étant contenu dans un sur-ensemble de la forme (un delta-dilaté). En nous appuyant sur nos précédents résultats portant sur les unions de boules, nous démontrons plusieurs propriétés de ces approximations. Nous verrons ainsi que calculer une approximation par boules à (delta,epsilon)-près qui soit de cardinal minimum est un problème NP-complet. Pour des formes simples dans le plan, nous présentons un algorithme polynomial en temps et en espace qui permet de calculer ces approximations de cardinal minimum. Nous concluons par une généralisation de notre méthode d'approximation pour une plus large variété de sous-ensembles et sur-ensembles. / Describing a complex geometric shape with a set of simple primitives is often a fundamental task for shape reconstruction, visualization, analysis and manipulation. The type of primitives, as well as the choice of approximation scheme, both greatly impact the properties of the resulting shape representation.In this PhD, we focus on balls as primitives. Using pencils of balls, we carefully describe finite unions of balls and their structure. In particular, our description holds in all dimension without assuming general position. On our way, we also establish various results and tools to test local and global inclusions within these unions.We also propose a new approximation scheme by union of balls, the (delta,epsilon)-ball approximation. This scheme constrains the approximation to cover a core subset of the original shape (specifically, an epsilon-erosion), while being contained within a superset of the shape (a delta-dilation). Using our earlier results regarding finite unions of balls, we prove several properties of these approximations. We show that computing a cardinal minimum (delta,epsilon)-ball approximation is an NP-complete problem. For simple planar shapes however, we present a polynomial time and space algorithm that outputs a cardinal minimum approximation. We then conclude by generalizing the approximation scheme to a wider range of core subsets and bounding supersets.