Accessibility of high-throughput genotyping technology makes possible genome-wide association studies for common complex diseases. When dealing with common diseases, it is necessary to search and analyze multiple independent causes resulted from interactions of multiple genes scattered over the entire genome. The optimization formulations for searching disease-associated risk/resistant factors and predicting disease susceptibility for given case-control study have been introduced. Several discrete methods for disease association search exploiting greedy strategy and topological properties of case-control studies have been developed. New disease susceptibility prediction methods based on the developed search methods have been validated on datasets from case-control studies for several common diseases. Our experiments compare favorably the proposed algorithms with the existing association search and susceptibility prediction methods.

<p>The development of fuel efficient internal combustion engines (ICE)have resulted in a variety of different solutions. One of those are the variable valve timing and an implemenation of such is the Continuous Variable Cam Phasing (CVCP). This thesis have used a simulation package, psPack, for the simulation of the gas exchange process for an ICE with CVCP. The purpose of the simulations was to investigate what kind of design parameters, e.g. the length of an intake pipe or the duration of combustion, that were significant for the gas exchange process with the alternation of intake pressure, engine speed and valve setting. The parameters that showed a vast impact were those who affected the amount of residual gas and the temperature of the air charge. Furthermore a validation was made between simulation data acquired from psPack and measured data provided in Heywood (1988). The validation showed that for the general behaviour the simulation results from psPack corresponded well to the measured data.</p>

Structural biology is a branch of science related to biochemistry, biophysics, and molecular biology that deals with the molecular structures of biological macromolecules, in particular nucleic acids and proteins. Structure-guided drug design uses three-dimensional knowledge of protein structures to design small molecules which block the action of specific proteins. When crystals of theses macromolecules and their complexes can be obtained, their crystal structures can be determined by using isomorphous differences between a native structure and a derivative structure. This allows crystallographers to determine the coordinates of a small number of heavy atoms which provide initial phases for macromolecules. The advent of synchrotron radiation allowed determination of a heavy atom substructure by use of anomalous differences using either multiple wavelengths (MAD) or a single wavelength (SAD); the latter has become the most common phasing method in crystallography and is the method used in this study. The use of SeMet has been by far the most successful method employed in SAD. However, in some cases production of SeMet proteins is not possible thus necessitating additional options, for example, xenon. Noble gases such as xenon may be used in SAD experiments by binding to various, non-specific sites. Advances in noble gas pressurization systems like the Hampton Research Xenon Chamber have greatly eased the production of noble gas derivatives, xenon itself being a prime candidate with a very strong anomalous signal when compared to lighter noble gases like krypton and argon. Investigation of the phasing properties of xenon was carried out on test proteins hen egg white lysozyme (HEWL), thermolysin, glucose isomerase, and thaumatin II. Phases were successfully determined for all four proteins including thaumatin II which did not bind xenon but was successful due to the anomalous signal from 17 native sulfurs. The three remaining proteins showed varying occupancies and numbers of sites including xenon sites in thermolysin and glucose isomerase which have not been observed previously. This document will serve as a guide for the preparation of xenon derivative crystals and provides a strategy for the collection and processing of data from xenon derivatives.

The development of fuel efficient internal combustion engines (ICE)have resulted in a variety of different solutions. One of those are the variable valve timing and an implemenation of such is the Continuous Variable Cam Phasing (CVCP). This thesis have used a simulation package, psPack, for the simulation of the gas exchange process for an ICE with CVCP. The purpose of the simulations was to investigate what kind of design parameters, e.g. the length of an intake pipe or the duration of combustion, that were significant for the gas exchange process with the alternation of intake pressure, engine speed and valve setting. The parameters that showed a vast impact were those who affected the amount of residual gas and the temperature of the air charge. Furthermore a validation was made between simulation data acquired from psPack and measured data provided in Heywood (1988). The validation showed that for the general behaviour the simulation results from psPack corresponded well to the measured data.

The GMT is an aplanatic Gregorian telescope consisting of 7 primary and secondary mirror segments that must be phased to within a fraction of an imaging wavelength to allow the 25.4 meter telescope to reach its diffraction limit. When operating in Laser Tomographic Adaptive Optics (LTAO) mode, on-axis guide stars will not be available for segment phasing. In this mode, the GMT's Acquisition, Guiding, and Wavefront Sensing system (AGWS) will deploy four pickoff probes to acquire natural guide stars in a 6-10 arcmin annular FOV for guiding, active optics, and segment phasing. The phasing sensor will be able to measure piston phase differences between the seven primary/secondary pairs of up to 50 microns with an accuracy of 50 nm using a J-band dispersed fringe sensor. To test the dispersed fringe sensor design and validate the performance models, SAO has built and commissioned a prototype phasing sensor on the Magellan Clay 6.5 meter telescope. This prototype uses an aperture mask to overlay 6 GMT-sized segment gap patterns on the Magellan 6.5 meter primary mirror reimaged pupil. The six diffraction patterns created by these subaperture pairs are then imaged with a lenslet array and dispersed with a grism. An on-board phase shifter has the ability to simulate an arbitrary phase shift within subaperture pairs. The prototype operates both on-axis and 6 arcmin off-axis either with AO correction from the Magellan adaptive secondary MagAO system on or off in order to replicate as closely as possible the conditions expected at the GMT.

This thesis explores the impacts and behavior of 3-phase distribution transformers when subject to ungrounded single phase open circuit faults. A simple 3-phase system is modeled using MATLAB Simulink and operation under fault conditions are simulated and studied. Simulation results are confirmed via lab experimentation. Finally, a robust detection and protection method using neutral current injection (as proposed in industry literature) is built and demonstrated. Electric utility operating experience has demonstrated that all too often, loads on 3-phase distribution transformers are not adequately protected against an ungrounded single phase open circuit fault (commonly called “single phasing”). This type of fault is amongst the least understood and hence the least protected against. This is especially true at end of transmission system radial feeds where 3-phase transformers can re-create the opened phase voltage due to a variety of effects including magnetic coupling, voltage loops and loading effects. Operating experience in the nuclear power industry has shown that the results can be catastrophic especially considering the impacts to motor loads. Impacts can result in unavailability of emergency loads, tripping of motor protection circuits or even motor damage and failure.

Between closely related species there are genomic regions with a higher level of differentiation compared to the rest of the genome. For a time it was believed that these regions harbored loci important for speciation but it has now been shown that these patterns can arise from other mechanisms, like recombination. The aim of this project was to estimate the recombination landscape for red-breasted flycatcher (Ficedula parva) and taiga flycatcher (F. albicilla) using patterns of linkage disequilibrium. For the analysis, 15 red-breasted and 65 taiga individuals were used. Scaffolds on autosomes were phased using fastPHASE and the population recombination rate was estimated using LDhelmet. To investigate the accuracy of the phasing, two re-phasings were done for one scaffold. The correlation between the rephases were weak on the fine-scale, and strong between means in 200 kb windows. 2,176 recombination hotspots were detected in red-breasted flycatcher and 2,187 in taiga flycatcher. Of those 175 hotspots were shared, more than what was expected by chance if the species were completely independent (31 hotspots). Both species showed a small increase in the rate at hotspots unique to the other species. The low number of shared hotspots might indicate that the recombination landscape is less conserved between red-breasted and taiga flycatchers than found between collared and pied flycatcher. However, the investigation of the phasing step indicate that the fine-scale estimation, on which hotspots are found, might not be reliable. For future analysis, it is important to use high-quality data and carefully chose methods.

Les sources lasers femtosecondes sont utilisées dans grand nombre d’applications (industrielles, médicales, de recherche fondamentale) avec un besoin croissant d’impulsions très énergétiques à haut taux de répétition. Bien que la technologie Ti:Saphir fournisse des impulsions PetaWatt, son taux de répétition s’avère limité. Une alternative est l’utilisation de la technologie fibrée. Cependant, l’énergie extractible d’une seule fibre est intrinsèquement limitée.Une solution prometteuse est alors de réaliser une combinaison de fibres (jusqu’à plus de 10 000 fibres pour l’accélération de particules). La combinaison de fibres par méthode interférométrique (avec un record de 64 fibres combinées en régime continu) a prouvé qu’elle était un excellent candidat pour la combinaison d’un grand nombre de fibres.La collaboration XCAN entre l’Ecole Polytechnique et Thales, vise à réaliser un démonstrateur de combinaison cohérente de 61 fibres amplifiées en régime femtoseconde. Les travaux menés au cours de cette thèse s’inscrivent dans ce projet.Dans un premier temps, afin d’étudier les points durs inhérents au régime femtoseconde tout en s’affranchissant des difficultés liées à l’amplification, la méthode interférométique en régime femtoseconde a été étudiée sur un démonstrateur passif, c’est-à-dire sans amplification, de 19 fibres. Une fois la méthode de mise en phase validée celle-ci a pu être testée avec succès sur le démonstrateur avec amplification du projet XCAN.Nous présentons également les travaux menés afin d’augmenter un paramètre clé des systèmes de combinaison de faisceaux à savoir : l’efficacité de combinaison du système laser. Pour cela, nous avons réalisé une mise en forme de faisceaux issus des fibres de la tête optique. Cette mise en forme, gaussien vers super-gaussien, est réalisée à l’aide de deux réseaux de lames de phase dont nous présenterons le calcul des profils asphériques. Afin de valider expérimentalement nos simulations et après réalisation des lames de phase nous avons pu tester celles-ci sur le démonstrateur passif, démontrant une augmentation de 14 %.Les travaux présentés dans ce manuscrit présentent ainsi les premiers par vers la réalisation d’une nouvelle architecture laser massivement parallèle, capable de délivrer à la fois une haute puissance crête et une haute puissance moyenne. / Femtosecond fiber sources are used in a large number of applications (industrial, medical, fundamental physics) with a growing need in high energy pulses at high repetion rate. Although Ti: Saphirre technology provides energies up to PetaWatt, its repetion rate is low (up to 1 Hz). An alternative is to use an amplified fiber. However, the extractable energy of a single fiber is intrinsically limited.A solution is then to combine several fibers (up to 10 000 fibers for particle acceleration). Coherent beam combining of fibers with an interferometric method (with a record of 64 fibers combined in the cw regime) has proven to be an excellent candidate to combine a large number of fibers.The XCAN project, a collaboration between l'Ecole polytechnique and Thales, aims to realize a demonstrator of 61 fibers coherently combined in the femtosecond regime.The works presented in this thesis are part of this project.In order to study the hard points inherent to the femtosecond regime and to free from the amplification issues, the interferometric method has been implemented on a passive demonstrator, meaning without amplification, of 19 fibers. Once the interferometric method validated, it has been succesfully tested on the amplified XCAN demonstrator.We present also the works done to increase a key parameter of beam combining systems : the combining efficiency. To do this, we have realized a beam shaping of the fiber array output beams. This beam shaping, gaussian to super-gaussian, is done with two arrays of phase plates. The aspherical profiles calculation is described. In order to validate our simulations we have tested the phase plates on the passive demonstrator by getting an increase of 14 %.The works presented in this manuscript are the first steps towards a new massively parallel laser architecture, able to provide both high peak power and high average power.

A conventional large aperture telescope required for binary star research is typically cost prohibitive. A prototype active optics system was created and fitted to a telescope frame using relatively low cost components. The active optics system was capable of tipping, tilting, and elevating the mirrors to align reflected star light. The low cost mirror position actuators have a resolution of 31 nm, repeatable to within 16 nm. This is accurate enough to perform speckle analysis for the visible light spectrum. The mirrors used in testing were not supported with a whiffletree and produced trefoil-like aberrations which made phasing two mirrors difficult. The active optics system was able to successfully focus and align the mirrors through manual adjustment. Interference patterns could not be found due to having no method of measuring the mirror surfaces, preventing proper mirror alignment and phasing. Interference from air turbulence and trefoil-like aberrations further complicated this task. With some future project additions, this system has the potential to be completely automated. The success of the active optics actuators makes for a significant step towards a fully automated sparse aperture telescope.

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