Consecutive traffic signals produce vehicle stops and acceleration/deceleration maneuvers on arterial roads, which may increase vehicle fuel consumption levels significantly. Eco-cooperative adaptive cruise control (Eco-CACC) systems can improve vehicle energy efficiency using connected vehicle (CV) technology. In this thesis, an Eco-CACC system is proposed to compute a fuel-optimized vehicle trajectory while traversing multiple signalized intersections. The proposed system utilizes signal phasing and timing (SPaT) information together with real-time vehicle dynamics data to compute the optimal acceleration/deceleration levels and cruise speeds for connected-technology-equipped vehicles while approaching and leaving signalized intersections, while considering vehicle queues upstream of the intersections. The INTEGRATION microscopic traffic simulation software was used to conduct a comprehensive sensitivity analysis of a set of variables, including different levels of CV market penetration rates (MPRs), demand levels, phase splits, offsets, and distances between intersections to assess the benefits of the proposed algorithm. Based on the analysis, fuel consumption saving increase with an increase in MPRs and a decrease in the cycle length. At a 100% equipped-vehicle MPR, the fuel consumption is reduced by as much as 13.8% relative to the base no Eco-CACC control. The results demonstrate an existence of optimal values for demand levels and the distance between intersections to reach the maximum fuel consumption reduction. Moreover, if the offset is near the optimal values for that specific approach, the benefits from the algorithm are reduced. The algorithm is limited to under-saturated conditions, so the algorithm should be enhanced to deal with over-saturated conditions. / Master of Science

L’instrumentation multi-pupille permet de repousser les limitations actuelles des diamètres des télescopes monolithiques. L’alignement des sous-pupilles est donc une problématique incontournable pour les futurs projets de télescopes au sol comme dans l’espace. Un Analyseur de Surface d’Onde (ASO) est alors nécessaire pour mesurer les aberrations spécifiques au cas multi-pupille que sont le piston différentiel (différence de marche entre les sous-pupilles), le tip et le tilt (basculements différentiels entre les sous-pupilles). Nous nous attachons à réaliser des ASOs non supervisés et simples d’implantation, permettant l’alignement total d’un instrument multi-pupille. L’algorithme ELASTIC repose sur l’analyse de la corrélation entre deux images focales prises successivement, différant par une perturbation maîtrisée et appliquée directement sur les sous-pupilles. ELASTIC permet d’une part d’estimer les grandes erreurs de tip/tilt, pour effectuer un alignement géométrique et d’autre part de stabiliser le tip/tilt pendant la minimisation des grandes erreurs de piston, pour l’alignement interférométrique. Enfin, un second algorithme appelé LAPD permet, au moyen de deux images prises simultanément dans un plan focal et dans un plan légèrement défocalisé, d’estimer les petites erreurs de piston/tip/tilt pour le cophasage fin. Ces différents algorithmes sont caractérisés au moyen de simulations numériques, pour différents types de télescopes multi-pupilles. Nous démontrons expérimentalement les briques de la chaîne d’alignement sur un instrument à 6 sous-pupilles. Ces ASOs permettent de simplifier le dimensionnement des futurs télescopes. / The resolution of a telescope is ultimately limited by its aperture diameter, but the size of mirrors is bounded by current technology to about 10m on the ground and to a few meters in space. To overcome this limitation, interferometry consists in making an array of sub-apertures interfere; the resulting instrument is called an interferometer or a multi-aperture telescope. To reach the diffraction limit of such instruments, all sub-apertures must be phased to within a small fraction of wavelength. A critical sub-system of interferometers is the Cophasing Sensor (CS), whose goal is to measure the relative positioning errors between the sub-apertures (differential piston, tip and tilt), which are the specific low-order aberration of an interferometer and the main source of wave-front degradation. We aim to develop unsupervised and easy-to-implement CSs for the global multi-aperture telescope alignment. ELASTIC algorithm provides a solution for large amplitude tip/tilt error measurement from a modified cross-spectrum of two diversity images, allowing the geometrical alignment. ELASTIC also provides tip/tilt stability for the large amplitude piston error minimization, called the interferometric alignment. Finally a second algorithm called LAPD uses focal and slightly defocused images for the small amplitude piston/tip/tilt error measurement, allowing the fine phasing. Numerical simulations of several types of multi-aperture telescopes are performed in order to test our algorithms. We experimentally demonstrate the efficiency of the different algorithms on a 6-sub-aperture instrument. These algorithms should simplify the design of the future telescopes.

A compound-heterozygous variant occurs when a child inherits a variant from each parent, with these variants occurring at a different position within the same gene and on opposite homologous chromosomes. These inherited variants may result in two nonfunctional versions of the same gene. Compound-heterozygous variants cannot be identified unless a patients' DNA sequence data is phased. Phasing is a computationally demanding process that requires the use of multiple software tools in order to determine which nucleotide was inherited from which parent. First, in Chapter 1, we review the literature to better understand what research has been conducted on the role of compound-heterozygous variants in pediatric cancers and what methods are being used to identify them. In Chapter 2, we develop a pipeline to make it easier for us and other researchers to phase and identify compound-heterozygous variants using VCF files from trios or individuals. We then use this pipeline in Chapter 3 to survey the prevalence of compound-heterozygous variants across 7 pediatric disease types. We show the importance of identifying compound heterozygous and what information would be missed if this variant type was not included in study design. In Chapter 4, we develop a software tool to phase trio data using a combination of Mendelian inheritance logic and an existing phasing software program. We show that our software tool increases the total number of variants that can be phased. Finally, in Chapter 5, we use phased data of three nuclear families, each family having one child with pediatric cancer, to evaluate the potential to use inherited genomic variants to inform diagnostic decisions. The work contained within this dissertation shows the importance of not overlooking compound-heterozygous variants when trying to identify potentially causal genes in pediatric disease. In addition, this work provides software tools that are openly available for other researchers to use; these tools make it easier to phase patient DNA sequence data and to identify compound-heterozygous variants.

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<p>NR 20140805</p>

Cette thèse concerne le développement de complexes de lanthanide et leur utilisation pour résoudre les structures de macromolécules biologiques par diffraction des rayons X, en particulier celles de protéines membranaires et de complexes protéiques de grande taille. Les complexes de lanthanide sont formés d’un atome de lanthanide et d’un ligand chimique qui assure une liaison non-covalente avec les surfaces protéiques. Introduits dans les cristaux de protéine, ces derniers constituent une sous-structure qui, déterminée par les méthodes de phasage de novo courantes, permet de résoudre la structure de la macromolécule d’intérêt. La première partie de ce travail de thèse est une étude menée sur la grande famille des complexes picolinates de lanthanide, complexes luminescents dont la fixation au sein des cristaux est aisément décelable. En premier lieu, nous avons défini les conditions dans lesquelles le complexe tris-dipicolinate de lanthanide peut être utilisé ainsi que ses éventuelles capacités à promouvoir la cristallisation (effet supramoléculaire). En second lieu, un nouveau complexe, dérivé du précédent, a été développé au cours de cette thèse : le tris-hydroxymethyltriazoledipicolinate de lanthanide (« [Ln(TDPA)3]3- »). Il nous a permis de réaliser un phasage de novo très précis conduisant à la détermination des structures du lysozyme de blanc d’œuf de poule et de la thaumatine de Thaumatococcus daniellii à haute résolution. Par ailleurs, différents ligands pour ce nouveau complexe ont été synthétisés par chimie-click, nous permettant de créer une panoplie de complexes uniques et des complexes hybrides. Nous avons montré que cette nouvelle famille de complexes présente une meilleure affinité pour les protéines permettant leur utilisation à de faibles concentrations. Les essais menés avec ces LnTDPA ont aussi permis d’entrevoir l’importance de la charge globale pour expliquer l’effet supramoléculaire. En troisième lieu, un tripicolinate cagé, le LnTNTPA, a également été évalué. Constitué d’une cage chimique de charge globale nulle, nous avons montré que ce nouveau complexe luminescent est le seul de cette famille picolinate qui puisse être utilisé en présence d’ions divalents. Dans la seconde partie de cette thèse, nous décrivons l’utilisation des complexes de lanthanide pour le phasage de protéines multimériques de grandes tailles par les méthodes de phasage de novo. Premièrement, la structure de l’aminopeptidase dodécamérique PhTET1-12s de 480 kDa a été déterminée à 4 Å de résolution à l’aide du tris-dipicolinate d’europium. Ceci nous a permis de démontrer que les complexes de lanthanide peuvent être utilisés pour obtenir un phasage précis, même à basse résolution. Deuxièmement, les complexes de lanthanide issus de l'imagerie médicale ont aussi permis de déterminer la structure de trois nouvelles enzymes homotétramériques de la famille des malate déshydrogénases. Ces structures permettent d’apporter de nouveaux éclaircissements sur l'adaptation halophile. Enfin, en utilisant ces enzymes en tant que bibliothèque de fonctions chimiques, nous avons pu mettre en place une nouvelle approche méthodologique pour comprendre finement les modes d'interaction des complexes de lanthanide. / This thesis aims to develop lanthanide complexes for solving biological macromolecular structures, especially membrane proteins and large protein complexes. Lanthanide complexes are composed of a lanthanide atom and a chemical ligand, which provides non-covalent binding to protein surfaces. Incorporated in protein crystals, they make up the substructure, determined by the widely-used de novo phasing methods, needed for solving the whole protein structure. The first part of the present work shows a study of the luminescent lanthanide picolinate complexes family, easily detectable in protein crystals. First, we defined the conditions in which the known lanthanide tris-dipicolinate can be used and we examined its possible ability to promote protein crystallization (supramolecular effect). Secondly, a newly developed lanthanide tris hydroxymethyltriazoledipicolinate complex "[Ln(TDPA)3]3-", derived from this previous complex, allowed us to obtain a very precise de novo phasing for solving the high-resolution structure of the hen egg white lysozyme and the thaumatin from Thaumatococcus daniellii. Besides, various ligands for these new complexes were synthetized by click chemistry, enabling us to create both unique complexes outfit and hybrid complexes. We have shown that this new complexes family presents a better affinity for proteins allowing their use at very low concentrations. Tests conducted with those LnTDPA have also evidenced the importance of complex global charge to explain the supramolecular effect. Third, a caged tripicolinate, the LnTNTPA, was evaluated. Characterized by a neutrally charged chemical cage, we have shown that this new luminescent complex is the only one of the picolinate complexes family that can be used in the presence of divalent ions. In the second part of this thesis, we describe the use of lanthanide complexes for phasing large multimeric proteins by de novo phasing methods. First, the structure of the 480 kDa dodecameric aminopeptidase PhTET1-12s was solved at 4 Å resolution by using the europium tris-dipicolinate which demonstrates that the lanthanide complexes can be used to obtain an accurate phasing, even at low resolution. Secondly, the lanthanide complexes from medical imaging also helped to solve the structures of three new homotetrameric enzymes from the malate dehydrogenases family. Those structures provide new insights into halophilic adaptation. Finally, by using these enzymes as a library of chemical functions, we developed a new methodological approach for a better understanding of the precise binding modes of those lanthanide complexes.

Left-turning maneuvers are considered to be the highest risk movements at intersections and two-thirds of the crashes associated with left-turns are reported at signalized intersections. Left-turning vehicles typically encounter conflicts from opposing through traffic. To separate conflicting movements, transportation agencies use a protected-only phase at signalized intersections where each movement is allowed to move alone. However, this could create delays and thus the concept of a protected-permissive phase has been introduced to balance safety and delays. However, the permissive part of this phasing scheme retains the safety concerns and could increase the possibility of conflicts resulting in crashes. This research developed a model that can predict the number of crashes for protected-permissive left-turn phasing, based on traffic volumes and calculated conflicts. A total of 103 intersections with permissive-protected left-turn phasing in Kentucky were simulated and their left-turn related conflicts were obtained from post processing vehicle trajectories through the Surrogate Safety Assessment Model (SSAM). Factors that could affect crash propensity were identified through the Principal Component Analysis in Negative Binomial Regression. Nomographs were developed from the models which can be used by traffic engineers in left-turn phasing decisions with enhanced safety considerations.

Prägnanz is a single movement composition for orchestra. This composition reflects the influence of minimalist composers such as Phillip Glass and Steve Reich. The structure of the piece is generated by a rhythmic motive that is transformed through a large-scale additive process. This overarching process is periodically interrupted by contrasting episodes, creating a form similar to a rondo. Several themes and gestures are explored, including a phasing rhythmic motive. The harmonic language is static, almost monolithic, in order to accentuate the gradual motion of the piece towards its goal. The title comes from Gestalt psychology; the Law of Prägnanz describes how the mind perceives simplicity within the complexity of reality. This tendency is mirrored in the piece through the focus on the central motivic transformation in spite of the complexity of contrasting themes, orchestrations, and gestures.

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