Radars, as the name suggests, were traditionally used for Radio Detection and Ranging. Nevertheless, advances in high resolution electromagnetic simulations, Ultra Wide-Band sources, signal processing and computer technologies have resulted in a possible perception of radars as sensors for target discrimination. In this thesis, the feasibility of discrimination between targets even with minor variations in structure and material composition on the basis of radar echoes is effectively demonstrated. It is well-known that the echoes from any target are affected by its natural frequencies which are dependent only on the shape and material composition of the target, and independent of the aspect angle or the incident waveform. The E-pulse technique is based on the fact that incident waveforms can be designed that uniquely annihilate the echoes from chosen regions of a target, and forms the basis of the method of discrimination proposed in this thesis. Earlier methods reported in the literature, effectively discriminated only between different classes of targets with substantial variations in the overall dimensions of the body. Discrimination of targets of the same class with a minor structural modification or with a material coating on specific areas was rather difficult. This thesis attempts and successfully validates a method which comprehensively addresses this problem. The key idea of this method is to use the higher frequency resonances (which characterise the finer details of a target) in the E-pulse technique. An obviously important aspect of target discrimination is therefore that of precisely estimating the natural frequencies for each target and understanding the changes in these frequencies, and their associations with the changes in structure and material composition. Current approaches to determine these frequencies are either based In the time or frequency domains. While the latter approach comprises the computation of the roots of a related determinantal equation, in the time domain, the natural frequencies are extracted from the response of a target to an impulse. Such a response can either be generated from actual experiments or by simulating the scattering response using Computational Electromagnetic (CEM) techniques. In this work, the impulse response is obtained from the frequency response of the scatterers in the frequency range of interest. Since no single CEM technique can effectively cover the entire range of frequencies needed for the E-Pulse synthesis. The Method of Moments and Physical Optics have been used for low and high frequency scattering respectively. The results obtained using the latter technique are validated by comparing with those obtained using Method of Moments at the transition frequencies and Geometrical Theory of Diffraction (GTD). The natural frequencies (i.e., poles of a corresponding transfer function) are extracted from the impulse response using Prony's algorithm. One of the parameters in this method is the number of such poles (i.e.. the order of the transfer function) present in the response, and the accuracy of the computed pole values depends on this assumed order. Here, the Hankel singular values of a transfer function is used to estimate the number of poles. This in turn implies that a specific norm of the error between a transfer function corresponding to the frequency response generated earlier, and a transfer function with an assumed order obtained using Prony's method is minimised. In the thesis, a wide range of target shapes are considered for purposes of illustration: wires, cylinders, spheres, plates and complex bodies such as aircraft, and the discrimination capability is demonstrated by introducing minor perturbations in their shape and/or material composition. .The following cases are considered here: (a) Wires: Conducting wires with a protrusion in one segment; conducting wire from another coated with a dielectric in a segment, (b) Cylinders: Conducting cylinders with one perturbed; conducting cylinders with a portion scrapped off in the middle, (c) Plates: Conducting plates with a elongation on one comer; conducting plate with another one with a hole in the centre, (d) Spheres: Conducting spheres with different radii; conducting spheres with Radar Absorbing Material coated spheres with different coating thickness; conducting spheres with chiral coated spheres with varying coating thickness, (e) Aircraft: Canonical model of MiG-29 aircraft from a similar one with stores placed under the wing.

La leucémie myéloïde aiguë (AML) est une forme agressive du cancer du sang qui est caractérisée par un haut taux de mortalité, tant chez les patients plus jeunes que plus âgés. Le développement de nouveaux traitements est ardu par l’hétérogénéité de cette maladie. Dans cette perspective, les études CCC phénotypiques menées à l’IRIC visent à déceler de nouveaux composés ayant une synergie contre des souches AML primaires de patients en vue de personnaliser les thérapies selon leur profil cytogénétique. Il a été découvert que le MG624, un antagoniste des récepteurs nicotiniques α7-nAChR inhibant la prolifération des cellules cancéreuses dans les SCLC, démontrait une activité spécifique contre la souche AML5. Dans cette recherche, les voies de synthèse des analogues du MG624 sont explorées afin de concevoir une série de sondes permettant d’identifier les cibles potentielles via une approche chimioprotéomique par affinité dans le lysat cellulaire. Cette méthode a permis d’identifier trois cibles potentielles à l’aide d’un essai par compétition et de contrôles négatifs, soit XIAP, NQO2 et U119B, toutes impliquées dans différentes formes de cancer. Ces expériences ont mené à une meilleure compréhension des motifs procurant l’activité du composé chez les cellules leucémiques. La synthèse d’une sonde par photoaffinité a ensuite été élaborée pour éventuellement lier les protéines identifiées de manière covalente dans l’environnement cellulaire natif afin de valider ces cibles. / Acute myeloid leukemia (AML) is an aggressive form of blood cancer characterized by a high mortality rate in both younger and older patients. The development of new treatments is hampered by the heterogeneity of this disease, which has led to the phenotypic CCC studies carried out at IRIC to identify new compounds that exhibit synergies against primary AML patient strains to personalize therapies according to their cytogenetic profile. MG624, an α7-nAChR nicotinic receptor antagonist that inhibits cancer cell proliferation in SCLC, was found to have specific activity against AML5. In this research, the synthetic pathways of MG624 analogues are explored to design a series of probes to identify potential targets via an affinity-based chemoproteomic approach in cell lysate. This method identified three potential targets using a competitive assay and negative controls, namely XIAP, NQO2 and U119B, all implicated in different forms of cancer. These experiments led to a better understanding of the motifs that provide the compound's activity in leukemic cells. A photo-affinity probe synthesis was then developed to covalently bind the identified proteins in the native cellular environment to eventually validate these targets.

Dans l'introduction, diverses voies de trafic intracellulaire et endocytose seront discutées. Je familiarise le lecteur avec des protéines inactivant les ribosomes, en mettant l'accent sur la structure, l'endocytose, et le trafic intracellulaire de la toxine bactérienne Shiga toxin (STX). STx et la ricine suivent la voie rétrograde pour exercer leur effet toxique sur les cellules. Ils sont respectivement, une menace maladie infectieuse pour la santé humaine et des outils potentiels pour le bioterrorisme pour lequel aucun antidote n’existe actuellement. D'un criblage à haut débit, Retro-1 et Retro-2 avaient déjà été identifiés comme de puissants inhibiteurs de la voie rétrograde à l'interface des endosomes précoces-TGN, et Retro-2 a été démontré pour protéger les souris contre la ricine. Parmi les facteurs de trafic analysés, seule la protéine SNARE syntaxine-5 a été ré- localisée dans les cellules traitées avec Rétro - 2. / In the introduction, various endocytic and intracellular trafficking pathways will be discussed. I acquaint the reader with ribosome-inactivating proteins, with emphasis on the structure, endocytosis, and intracellular trafficking of the bacterial toxin Shiga toxin (STx). STx and ricin follow the retrograde route to exert their toxic effect on cells. They are respectively, an infectious disease threat to human health and potential tools for bioterrorism for which no antidote currently exists. From a high throughput screening, Retro-1 and Retro-2 had previously been identified as potent inhibitors of the retrograde route at the early endosomes-TGN interface, and Retro-2 was demonstrated to protect mice against ricin. Of the trafficking factors analyzed, only the SNARE protein syntaxin-5 was re-localized in Retro-2 treated cells. Yet, whether syntaxin-5 is the direct target of Retro-2 and whether its re-localization was directly responsible for retrograde transport inhibition remained to be established.