Le cancer est la cause la plus fréquente de décès dans le monde, avec 8,2 millions de décès par an. Des études génomiques à grande échelle ont montré que chaque tumeur est caractérisée par un profil génomique unique, conduisant au développement de la médecine de précision, où le traitement est adapté aux altérations génomiques de la tumeur du patient. Dans le cancer du sein précoce HR+/HER2-, les caractéristiques clinicopathologiques des patientes, bien qu’elles aient une valeur pronostique claire, ne sont pas suffisantes pour expliquer entièrement le risque de rechute à distance. L'objectif principal de ce projet de thèse était de déterminer les altérations génomiques impliquées dans la rechute à distance, en plus des paramètres cliniques des patientes, en utilisant des méthodes statistiques et informatiques. Ce projet a été réalisé à partir de données cliniques et génomiques (nombre de copies et mutations) issues des études PACS04 et METABRIC.Dans la première partie de mon projet de thèse, j’ai tout d’abord évalué la valeur pronostique du nombre de copies de gènes prédéfinis (FGFR1, Fibroblast Growth Factor Receptor 1 ; CCND1, Cyclin D1 ; ZNF217, Zinc Finger protein 217 ; ERBB2 ou HER2, Humain Epidermal Growth Factor) ainsi qu’un panel de mutations de gènes « driver ». Les résultats de l’étude PACS04 ont montrés que l’amplification de FGFR1 augmente le risque de rechute à distance alors que les mutations de MAP3K1 diminuent le risque de rechute. Ensuite, un score génomique fondé sur FGFR1 et MAP3K1 a été créé et a permis de déceler trois niveaux de risques de rechute à distance : risque faible (patientes ayant une mutation du gène MAP3K1), risque modéré (patientes n’ayant pas d’altération du nombre de copies de FGFR1 et n’ayant pas de mutation de MAP3K1) et risque élevé (patientes ayant une amplification de FGFR1 et n’ayant pas de mutation de MAP3K1). Enfin, ce score génomique a été validé sur une base de données publique, METABRIC. Dans la seconde partie de mon projet de thèse, de nouveaux biomarqueurs génomiques pronostiques de la survie ont pu être identifiés grâce aux méthodes pénalisées de type LASSO, prenant en compte la structure en bloc des données.Mots-clés : Altération du nombre de copies, mutations, cancer du sein, biomarqueurs, méthode de sélection de variables, réduction de dimension, modèle de Cox / Cancer is the most frequent cause of death in the world, with 8.2 million death / year. Large-scale genome studies have shown that each cancer is characterized by a unique genomic profile. This has led to the development of precision medicine, which aims at targeting treatment using tumor genomic alterations that are patient-specific. In hormone-receptor positive/human epidermal growth factor receptor-2 negative early breast cancer, clinicopathologic characteristics are not sufficient to fully explain the risk of distant relapse, despite their well-established prognostic value. The main objective of this thesis project was to use statistical and computational methods to assess to what extent genomic alterations are involved in distant breast cancer relapse in addition to classic prognostic clinicopathologic parameters. This project used clinical and genomic data (i.e., copy numbers and driver gene mutations) from the PACS04 and METABRIC trial.In the first part of my thesis project, I first evaluated prognostic value of copy numbers of predefined genes including FGFR1, Fibroblast Growth Factor Receptor 1; CCND1, Cyclin D1; ZNF217, Zinc Finger Protein 217; ERBB2 or HER2, Human Epidermal Growth Factor, as well as a panel of driver gene mutations. Results from the PACS04 trial showed that FGFR1 amplification increases the risk of distant relapse, whereas mutations of MAP3K1 decrease the risk of relapse. Second, a genomic score based on FGFR1 and MAP3K1, allowed to identify three levels of risk of distant relapse: low risk (patients with a MAP3K1 mutation), moderate risk (patients without FGFR1 copy number aberration and without MAP3K1 mutation) and high risk (patients with FGFR1 amplification and without MAP3K1 mutation). Finally, this genomic score was validated in METABRIC, a publicly available database. In the second part of my thesis project, new prognostic genomic biomarkers of survival were identified using penalized methods of LASSO type, taking into account the block structure of the data.Keywords: Copy number aberrations (CNA), mutations, breast cancer (BC), biomarkers, variable selection methods, dimension reduction, cox regression

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This thesis has two aims. The first one is the investigation and analysis of the errors occurring in the measurements with pulsed time-of-flight (TOF) terrestrial laser scanners (TLS). A good understanding of the error sources and the relationships between them is necessary to secure the data accuracy. We subdivide these errors into four groups: instrumental, object-related, environmental and methodological. Based on our studies and the results obtained by other researchers, we have compiled an error model for TLS, which is used to estimate the single-point coordinate accuracy of a point in the point cloud, transformed to the specified coordinate system. The second aim is to investigate systematic instrumental errors and performance of three pulsed TOF laser scanners – Callidus 1.1, Leica HDS 3000 and Leica HDS 2500 – and to develop calibration procedures that can be applied by the users to determine and correct the systematic errors in these instruments. The investigations have been performed at the indoor 3D calibration field established at KTH and outdoors. The systematic instrumental errors, or calibration parameters, have been estimated in a self-calibration according to the parametric least-squares adjustment in MATLAB®. The initial assumption was that the scanner instrumental errors are similar to those in a total station. The results have shown that the total station error model is applicable for TLS as a first approximation, but additional errors, specific to the scanner design, may appear. For example, we revealed a significant vertical scale error in the scanner Callidus 1.1, caused by the faults of the angular position sensor. The coordinate precision and accuracy of the scanners, estimated during the self-calibration, is at the level of several millimetres for Callidus 1.1 and Leica HDS 3000, and at the submillimetre level for Leica HDS 2500. In other investigations, we revealed a range drift of up to 3 mm during the first few hours of scanning, presumably due to the changes in the temperature inside the scanners. The angular precision depends on the scanner design (“panoramic” or “camera-like”), and the angular accuracy depends on the significant calibration parameters in the scanner. Investigations of the influence of surface reflectance on the range measurements have shown that the indoor illumination and surface wetness have no tangible influence on the results. The type of the material does not affect, in general, the ranging precision for Callidus 1.1, but it affects the ranging precision and accuracy of the scanners Leica HDS 3000 and Leica HDS 2500. The reason may be different wavelength and, possibly, different design of the electronics in the laser rangefinders. Materials with high reflectance and those painted with bright “warning” colours may introduce significant offsets into the measured ranges (5 – 15 cm), when scanned from close ranges at normal incidence with the scanner Leica HDS 3000. “Mixed pixels” at the object edge may introduce a range error of several centimetres, on the average, depending on the type of the material. This phenomenon leads also to the distortions of the object size, which may be reduced by the removal of the “mixed pixels” based on their intensity. The laser beam intensity recorded by the scanner tends to decrease with an increased incidence angle, although not as assumed by the popular Lambertian reflectance model. Investigations of the scanner Leica HDS 2500 outdoors have revealed no significant influence of the “normal” atmospheric conditions on the range measurements at the ranges of up to 50 m. Finally, we have developed and tested two simple procedures for the calibration of the vertical scale (and vertical index) error and zero error in laser scanners. We have also proposed an approach for the evaluation of the coordinate precision and accuracy in TLS based on the experiences from airborne laser scanning (ALS). / QC 20101123

Precision medicine is an emerging approach for disease treatment and prevention that delivers personalized care to individual patients by considering their genetic make- ups, medical histories, environments, and lifestyles. Despite the rapid advancement of precision medicine and its considerable promise, several underlying technological chal- lenges remain unsolved. One such challenge of great importance is the security and privacy of precision health–related data, such as genomic data and electronic health records, which stifle collaboration and hamper the full potential of machine-learning (ML) algorithms. To preserve data privacy while providing ML solutions, this thesis explores the feasibility of machine learning with encryption for precision healthcare datasets. Moreover, to ensure audit logs’ integrity, we introduce a blockchain-based secure logging architecture for precision healthcare transactions. We consider a sce- nario that lets us send sensitive healthcare data into the cloud while preserving privacy by using homomorphic encryption and develop a secure logging framework for this precision healthcare service using Hyperledger Fabric. We test the architecture by generating a considerable volume of logs and show that our system is tamper-resistant and can ensure integrity. / Graduate

The collective body of U.S. legislation, colloquially known as the Farm Bill, authorizes a suite of practices and programs under its Conservation Title. This includes the Conservation Reserve Program (CRP), which incentivizes agricultural producers to remove arable land from production to enhance soil retention, improve water quality, and restore wildlife habitat. Conservation Practice 33: Habitat Buffers for Upland Birds (CP-33) was the first CRP practice to target wildlife habitat restoration. CP-33 incentivizes producers to reestablish native herbaceous vegetation along crop field margins. Producers are often concerned with the economic opportunity costs of CP-33 enrollment. I used yield data derived from 44 agricultural fields in the Mississippi Alluvial Valley, USA to compare the environmental and economic opportunities associated with CP-33 establishment. I used yield data to develop a revenue distribution function to illustrate CP-33 revenue as commodity prices fluctuate. I found that as commodity prices increase, CP-33 implementation becomes less profitable.

Intense agriculture is detrimental to the environment and leads to nutrient runoff, decreased water quality, soil erosion, greenhouse gas emissions, and decreased wildlife habitat. In addition to negative environmental impacts, intense agriculture increases the financial strain on farmers. Farmers also face inconsistent yields from environmentally vulnerable lands. Due to these financial constraints and inconsistent yields, conservation goals are not always economically attractive to farmers and agricultural producers. One possible solution to this issue is the use of precision agriculture (PA) to inform strategic conservation efforts. We used PA technology to identify low-revenue field areas in the Mississippi Delta and Black Prairie regions. We created spatially explicit revenue maps and overlaid it with the Biologist Ranking Index (BRI) to illustrate where economic and conservation opportunities overlap. Our results indicate that, on average, upwards of 20.1% of the Black Prairie and 18.0% of the Mississippi Delta generate less revenue than conservation enrollment.

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An increasing number of mechanical systems are being designed on the micro and meso scales. Assembly and maintenance become increasingly difficult as the size of mechanisms decrease, and the minimum size of traditional elements such as bearings and springs is limited. The backlash of bearings also limits their usefulness in applications where high precision and repeatability are needed. At small scales and for high precision applications, alternative, non-traditional elements are needed. The objective of this thesis is to develop reliable and scalable compliant components to replace bearings and helical springs. Components replacing springs must be able to produce specified torque/motion requirements. Components replacing bearings must permit sufficient motion about the axis of rotation, bear specified loads in the lateral directions, and fit within roughly the same design space as a bearing. Additionally, all components will be designed to be manufactured using in-plane fabrication processes. Practical application of the components will be demonstrated by their use in Sandia National Laboratory's Stronglink assembly. The concepts discussed in this thesis fall into three categories: mechanisms that replace 1) the helical spring, 2) the bearing, and 3) both the helical spring and the bearing. The serpentine flexure belongs to the first category, the compliant rolling-contact element (CORE), CORE bearing, and elliptical CORE bearing belong to the second, and the compliant contact-aided revolute (CCAR) joint belongs to the third category.