Centered finite difference is the basic method in this paper for spatial discretization. In general, except the schemes that will be used adjacent tothe boundary points, centered finite difference schemes will be used on the main mesh points. Depending on the requirement of order of accuracy and optimization, different multi-point stencil schemes will be built in Matlab in the form of matrix. As a result, solving PDEs is actually operating matrices in Matlab. Standard schemes and optimized schemeswill be tested with 1D linear convection equation before applying them to the solvers. In 2D-pulse case, the rectangular domain will be transformed into a wavy domain and as a result Jacobian transformation method will betested. Results from different schemes will be compared with the analytical solution in two dimensional pulse case.

Signal detection from Adverse Event Reports (AERs) is important for identifying and analysing drug safety concern after a drug has been released into the market. A safety signal is defined as a possible causal relation between an adverse event and a drug. There are a number of safety signal detection algorithms available for detecting drug safety concern. They compare the ratio of observed count to expected count to find instances of disproportionate reportings of an event for a drug or combination of events for a drug. In this thesis, we present an algorithm to mine the AERs to identify drugs which show sudden and large changes in patterns of reporting of adverse events. Unlike other algorithms, the proposed algorithm creates time series for each drug and use it to identify start of a potential safety problem. A novel vectorized timeseries utilizing multiple attributes has been proposed here. First a time series with a small time period was created; then to remove local variations of the number of reports in a time period, a time-window based averaging was done. This method helped to keep a relatively long time-series, but eliminated local variations. The steps in the algorithm include partitioning the counts on attribute values, creating a vector out of the partitioned counts for each time period, use of a sliding time window, normalizing the vectors and computing vector differences to find the changes in reporting over time. Weights have been assigned to attributes to highlight changes in the more significant attributes. The algorithm was tested with Adverse Event Reporting System (AERS) datasets from Food and Drug Administation (FDA). From AERS datasets the proposed algorithm identified five drugs that may have safety concern. After searching literature and the Internet it was found that the five drugs the algorithm identified, two were recalled, one was suspended, one had to undergo label change and the other one has a lawsuit pending against it.

En dépit des progrès réalisés ces dernières décennies, le cancer demeure un problème majeur de santé publique. La plupart des chimiothérapies conventionnelles exploitent les propriétés cytotoxiques d'agents non sélectifs qui affectent les cellules à division rapide, qu'elles soient cancéreuses ou non, ce qui peut aboutir à une toxicité importante et de sévères effets secondaires. Pour pallier à ce problème, l'utilisation de ligands de ciblage pour délivrer spécifiquement l'agent cytotoxique aux cellules malignes tout en épargnant les tissus sains est une approche prometteuse. Parmi les différents ligands exploités, l'acide folique fait l'objet d'une attention particulière due à la surexpression préférentielle de son récepteur par de nombreux types de cellules cancéreuses. Cependant, les essais cliniques menés sur des molécules reposant sur cette stratégie indiquent que leur efficacité dépend surtout du niveau d'expression du récepteur ciblé. Dans ce contexte, j'ai développé deux approches permettant d'augmenter l'efficacité du ciblage des récepteurs à l'acide folique. D'une part, j'ai réalisé la validation biologique de nouveaux conjugués conçus pour délivrer conjointement deux agents anticancéreux. D'autre part, j'ai mis au point un traitement capable d'augmenter, in vitro et in vivo, l'expression des récepteurs à l'acide folique à la surface des cellules tumorales. Cela aboutit à l'internalisation d'une plus grande quantité de vecteur, qui se traduit in vivo, par une inhibition plus importante de la croissance tumorale, sans toxicité sur les cellules saines. / Despite significant advances obtained during the last decades, cancer is still lack of effective treatments. Indeed, most conventional chemotherapies relies on non-selective agents that kill indifferently healthy and tumor cells with high rate of division. This can lead to elevated toxicity and severe side effects. In this context, therapeutic approaches that exploit targeting ligands to selectively deliver cytotoxic drugs to malignant cells are currently promising. Among these different ligands, folate conjugates are subject to special attention due to the preferential overexpression of the folate receptor on several human cancer cell types that can mediate specific attachment and internalization of folate-derived imaging and therapeutic agents. However, clinical trials carried on such molecules revealed that their efficiency is mainly governed by folate receptor expression level on tumor cells. In this respect, I developed two approaches to increase efficacy of folate receptor targeting. On one hand, I realized biological validation of new targeting devices designed for the simultaneous delivery of two therapeutic agents. On the other hand, I developed a treatment to enhance in vitro and in vivo folate receptor expression at the surface of malignant cells. This treatment allows the internalization of a larger amount of a folic acid conjugate, previously synthesized and validated in our laboratory. That results in a drastically improvement of the in vivo tumor growth inhibition, without toxicity toward healthy cells.

The Single Instruction Multiple Data (SIMD) paradigm became a core principle for optimizing query processing in columnar database systems. Until now, only the LOAD/STORE instructions are considered to be efficient enough to achieve the expected speedups, while avoiding GATHER/SCATTER is considered almost imperative. However, the GATHER instruction offers a very flexible way to populate SIMD registers with data elements coming from non-consecutive memory locations. As we will discuss within this article, the GATHER instruction can achieve the same performance as the LOAD instruction, if applied properly. To enable the proper usage, we outline a novel access pattern allowing fine-grained, partition-based SIMD implementations. Then, we apply this partition-based SIMD processing to two representative examples from columnar database systems to experimentally demonstrate the applicability and efficiency of our new access pattern.

This thesis focuses on the development of tools and methods dedicated for ultra wide band (UWB) localization systems in indoor environment. The thesis work was conducted within the European FP7 project Where2, about the cooperative localization in cellular networks. Data from a measurement campaign conduct during the project are used to validate the proposed algorithms. This thesis is divided in four parts : The first part is focused on the description of an original raytraing tool based on a graph description. In order to be compliant with the requirement of a mobile simulation, a new concept of rays signature enabling incremental computation, and a vectorized formalism for processing rays are described and implemented. The second part is focused on the indoor localization techniques, where a novel technique based on interval analysis approaches is presented and compared to alternative techniques. Advantageously using this approach, a specific processing based on an hypothesis testing method using received power observations to resolve ambiguities appearing in under determined localization problems is described. A third part describes different aspects of the dynamic platform. In particular a realistic mobility model based on ''steering behaviors'', a graph description of the network scene and an inter agents communication protocol are detailed. The fourth section uses measured data obtained from an heterogeneous measurement campaign to validate both the developed software platform and the proposed localization algorithms.

Cette thèse porte sur le développement d'outils et de méthodes pour l'étude des systèmes de localisation Ultra Large Bande en milieu intérieur. Le travail de thèse a été mené pour partie dans le cadre du projet Européen FP7 WHERE2, portant sur la localisation coopérative dans les réseaux cellulaires. La thèse utilise pour sa partie validation des données obtenues dans le cadre de ce projet. La thèse comporte 4 grandes parties. Une première partie présente un outil de raytracing basé sur une description à base de graphes. Afin de pouvoir adresser les problématiques de simulation de la mobilité, l'outil introduit le concept nouveau de signature ainsi qu'un formalisme vectorisé permettant l'accélération du calcul du champ sur les rayons obtenus. Une seconde partie concerne les techniques de localisation utilisées en intérieur et propose une technique originale basée sur des approches ensemblistes. Cette technique est évaluée et comparée à des techniques alternatives comme le des moindres carrés pondérés ou le maximum de vraisemblance. Tirant partie des spécificités de la méthode précédente, une méthode basé sur un test d'hypothèse est décrite. Cette dernière propose d'exploiter les données de puissance reçue (largement disponible en pratique) pour lever les ambiguïtés multimodales dans les cas de carence d'observables précis. Une troisième partie présente 3 aspects de la plateforme dynamique. Tout d'abord un modèle de mobilité réaliste basé sur les «steering behaviors», puis la description sous forme de graphe du réseaux sans fils et enfin un protocole simplifié de communication inter agents. La quatrième partie exploite des données radio obtenues lors d'une campagne de mesure pour valider les différents étages de la plateforme et les algorithmes de localisation proposés. / This thesis focuses on the development of tools and methods dedicated for ultra wide band (UWB) localization systems in indoor environment. The thesis work was conducted within the European FP7 project Where2, about the cooperative localization in cellular networks. Data from a measurement campaign conduct during the project are used to validate the proposed algorithms. This thesis is divided in four parts : The first part is focused on the description of an original raytraing tool based on a graph description. In order to be compliant with the requirement of a mobile simulation, a new concept of rays signature enabling incremental computation, and a vectorized formalism for processing rays are described and implemented. The second part is focused on the indoor localization techniques, where a novel technique based on interval analysis approaches is presented and compared to alternative techniques. Advantageously using this approach, a specific processing based on an hypothesis testing method using received power observations to resolve ambiguities appearing in under determined localization problems is described. A third part describes different aspects of the dynamic platform. In particular a realistic mobility model based on ''steering behaviors'', a graph description of the network scene and an inter agents communication protocol are detailed. The fourth section uses measured data obtained from an heterogeneous measurement campaign to validate both the developed software platform and the proposed localization algorithms.