Biotechnological inventions during the 20th century have resulted in a wide range of approaches for explorations in the functional genomics field. Microarray technology is one of the recent advances which have provided us with snapshots of which genes are expressed in cells of various tissues and diseases. Methods to obtain reliable microarray data are continuously being developed and improved to meet the demands of biological researchers. In this thesis microarrays have been used to investigate gene expression patterns in cancer research. Four studies in three different areas were carried out covering adrenocortical tumors, p53 target genes and a comparison of RNA amplification methods. Adrenocortical tumours are among the most common tumours with an incidence of 7-9%. Malignancy of these tumors is rare. Distinction between malignant and benign tumours is often difficult to establish which makes an improvement of diagnostic approaches important. To elucidate biological processes in adrenocortical tumour development and to examine if there is a molecular signature associated with malignancy, microarray analysis was performed on 29 adrenocortical tumors and four normal specimens. It was possible to classify malignant and benign samples based on the entire expression profile. A number of potential biomarkers was identified which will be further evaluated. P53 is a gene which is mutated in 50% of all cancers. Functional p53 is a transcription factor which is activated upon cellular stress and DNA damage. Target genes are mainly involved in cell cycle arrest and apoptosis. In solid tumors cells are stressed by hypoxia. To examine which target genes p53 activate under hypoxic conditions a microarray study of the cell lines HCT116p53+/+ and HCT116p53-/- was performed. A set of novel potential p53 target genes was identified while many known target genes were found to be not transcriptionally activated during hypoxia. Follow up which was focused on how p53 affected hypoxia induced apoptosis showed that the death receptor Fas was critical. When small amounts of tissue are available, amplification of the transcript population is necessary for microarray analysis. A new strategy for amplification based on PCR was evaluated and compared to a commercial in vitro transcription protocol. Both protocols produced reliable results. Advantages with the PCR based method are a lower cost and a high flexibility due to compatibility with both sense and antisense strand microarrays. Keywords: adrenocortical tumour, apoptosis, cancer, classification, gene expression, microarray, p53, RNA amplification / QC 20100907

This thesis explores the use of engineered nonlinear crystals from the KTiOPO4 (KTP) family as the gain material in optical parametric amplifiers (OPAs), with the aim to achieve more knowledge about the benefits and limitations of these devices. The work aims further at extending the possible applications of OPAs by constructing and investigating several efficient and well performing amplifiers. An OPA consists of a strong pump source, which transfers its energy to a weak seed beam while propagating through a nonlinear crystal. The crystals employed in this work are members of the KTP family, which are attractive due to their large nonlinear coefficients, high resistance to damage and wide transparency range. The flexibility of OPAs with respect to different wavelength regions and pulse regimes was examined by employing various dissimilar seed and pump sources. The possibility to adapt an OPA to a specific pump and seed wavelength and achieve efficient energy conversion between the beams, originates from quasi-phasematching, which is achieved in periodically poled (PP) nonlinear crystals. Quasi-phasematched samples can be obtained by changing the position of certain atoms in a ferroelectric crystal and thereby reversing the spontaneous polarisation. In this thesis several material properties of PP crystals from the KTP family were examined. The wavelength and temperature dispersion of the refractive index were determined for PP RbTiOPO4, which is essential for future use of this material. Another experiment helped to increase the insight into the volumes close to domain walls in PP crystals Further, several OPAs were built and their ability to efficiently amplify the seed beam without changing its spectral or spatial properties was studied. Small signal gains of up to 55 dB and conversion efficiencies of more than 35 % were achieved for single pass arrangements employing 8 mm long PPKTP crystals. Apart from constructing three setups, which generated powerful nanosecond, picosecond and femtosecond pulses, the possibility to amplify broadband signals was investigated. An increase of the OPA bandwidth by a factor of approximately three was achieved in a noncollinear configuration. / QC 20101013

Main objective of this study is to design a compliant mechanism with high frequency and high mechanical amplification ratio to be used for amplifying the stroke of a piezostack actuator. In this thesis, first of all, related literature is investigated and then alternative conceptual designs are established utilizing the mechanisms found in literature survey. Once best conceptual design is selected, detailed design of this mechanism is done. For detailed design of the compliant mechanism, topology optimization method is used in this study. To design the mechanism, first a design domain is defined and then a finite element model of the design domain is prepared to be used in topology optimization runs. After running the topology optimization model by using TOSCA with ANSYS, results are imported to ANSYS, where final performance of the mechanism design is checked. After finalizing design of the mechanism, it is produced and its performance is tested through experiments.

Main objective of this study is to design a compliant mechanism with high frequency and high mechanical amplification ratio to be used for amplifying the stroke of a piezostack actuator. In this thesis, first of all, related literature is investigated and then alternative conceptual designs are established utilizing the mechanisms found in literature survey. Once best conceptual design is selected, detailed design of this mechanism is done. For detailed design of the compliant mechanism, topology optimization method is used in this study. To design the mechanism, first a design domain is defined and then a finite element model of the design domain is prepared to be used in topology optimization runs. After running the topology optimization model by using TOSCA with ANSYS, results are imported to ANSYS, where final performance of the mechanism design is checked. After finalizing design of the mechanism, it is produced and its performance is tested through experiments.

Surface plasmon-polaritons are optical surface waves formed through the interaction of photons with free electrons at the surface of metals. They offer interesting applications in a broad range of scientific fields such as physics, chemistry, biology, and material science. However, many of such applications face limitations imposed by the high propagation losses of these waves at visible and near-infrared wavelengths, which result mainly from power dissipation in the metal. In principle, the propagation losses of surface plasmon-polaritons can be compensated through optical amplification. The objective of this thesis is to provide deeper insights on the physics of surface plasmon-polariton amplification and spontaneous emission in surface plasmon-polariton amplifiers through theoretical and experimental vehicles applied (but not necessarily restricted) to a particular plasmonic mode termed long-range surface plasmon-polariton. On the theoretical side, the objective is approached by developing a realistic theoretical model to describe the small-signal amplification of surface plasmon-polaritons in planar structures incorporating dipolar gain media such as organic dye molecules, rare-earth ions, and quantum dots. This model takes into account the inhomogeneous gain distribution formed near the metal surface due to a non-uniform excitation of dipoles and due to a position-dependent excited-state dipole lifetime that results from near-field interactions between the excited dipoles and the metal. Also, a theoretical model to describe the amplified spontaneous emission of surface plasmon-polaritons supported by planar metallic structures is developed. This model takes into account the different energy decay channels into which an exited dipole located in the vicinity of the metal can relax. The validity of this model is confirmed through experimentation. On the experimental side, the objective is approached by providing a direct experimental demonstration of complete loss compensation in a plasmonic waveguide. The experiments are conducted using the long-range surface plasmon-polariton supported by a symmetric thin gold waveguide incorporating optically pumped organic dye molecules in solution as the gain medium. Also, an experimental study of spontaneous emission in a long-range surface plasmon-polariton amplifier is presented. It is shown that this amplifier benefits from a low spontaneous emission into the amplified mode, which leads to an optical amplifier with low noise characteristics. The experimental setup and techniques are explained in detail.

A new design synthesis method for articulated heavy vehicles (AHVs) with an active trailer steering (ATS) system is examined and evaluated. Due to their heavy weights, large sizes, and complex configurations, AHVs have poor maneuverability at low speeds, and low lateral stability at high speeds. Various passive trailer steering and ATS systems have been developed for improving the low-speed maneuverability. However, they often have detrimental effects on the high-speed stability. To date, no systematic design synthesis method has been developed to coordinate the opposing design goals of AHVs. In this thesis, a new automated design synthesis approach, called a Single Design Loop (SDL) method, is proposed and investigated. The SDL method has the following distinguished features: 1) the optimal active design variables of ATS systems and the optimal passive vehicle design variables are searched in a single design loop; 2) in the design process, to evaluate the vehicle performance measures, a driver model is developed and it „drives‟ the vehicle model based on the well-defined testing specifications; and 3) the ATS controller derived from this method has two operational modes: one for improving the lateral stability at high speeds and the other for enhancing path-following at low speeds. To demonstrate the effectiveness of the new SDL method, it is applied to the design of an ATS system for an AHV with a tractor/full-trailer. In comparison to a conventional design approach, the SDL method can search through solutions in a much larger design space, and consequently it provides a more comprehensive set of optimal designs.. / UOIT

Le premier chapitre de ce mémoire intitulé "Amplificateurs faible bruit accordés pour systèmes intégrés CMOS" s'intéresse aux méthodes de conception permettant l'intégration complète de l'amplificateur faible bruit d'une (LNA) depuis la gamme des radiofréquences jusqu'à la gamme des fréquences millimétriques. Ces travaux ont été menés dans le cadre de la Thèse de Mathieu Egels et dans le cadre d'une convention de recherche avec la société ST-Microélectronics financée par le Conseil Général des Bouches du Rhône. Le deuxième chapitre est intitulé "Amplificateurs bas niveau large bande pour systèmes intégrés CMOS". Ce chapitre présente les solutions que nous avons développées au laboratoire qui permettent de contrôler la bande passante des amplificateurs faible bruit pour systèmes intégrés destinés aux applications utilisant les normes UWB ainsi que des études plus prospectives sur l'amplification distribuée CMOS pour des applications à très grandes bandes passantes. Dans la dernière partie de ce chapitre nous décrivons nos travaux concernant la mise en boîtier des circuits et systèmes intégrés haute fréquence et large bande. Ces différents travaux ont été réalisés d'une part dans le cadre des Thèses de Mathieu Egels, et de Marc Battista, dans le cadre d'une convention de recherche avec la société ST-Microélectronics financée par le Conseil Général des Bouches du Rhône, et d'autre part dans le cadre de la thèse de Romen Cubillo avec le soutien de la plateforme conception du Centre Intégré de Microélectronique de la région PACA (CIMPACA). Le troisième chapitre "Convertisseurs RF/DC pour la téléalimentation haute fréquence en RFID" décrit nos activités de recherche concernant les circuits et architectures pour la télé-alimentation des circuits intégrés au moyen d'une onde électromagnétique. Les applications ciblées concernent essentiellement les étiquettes électroniques sans contact dans le domaine des fréquences UHF pour lesquelles nous avons développé des circuits et des architectures pour les technologies CMOS standard. Ces travaux ont été réalisés dans le cadre de la Thèse de Emmanuel Bergeret dans le cadre d'une convention de recherche avec la société ST-Microélectronics soutenue par le Conseil Général des Bouches du Rhône. Dans ce mémoire nous nous attacherons à décrire l'état de l'art des différents thèmes de recherche abordés et à situer nos travaux vis-à-vis de cet état de l'art. Le détail de nos travaux de recherche étant disponible dans les différents articles et thèses référencés, nous donnerons dans ce mémoire uniquement les grandes lignes de nos études et les principaux résultats obtenus.

Surface plasmon-polaritons are optical surface waves formed through the interaction of photons with free electrons at the surface of metals. They offer interesting applications in a broad range of scientific fields such as physics, chemistry, biology, and material science. However, many of such applications face limitations imposed by the high propagation losses of these waves at visible and near-infrared wavelengths, which result mainly from power dissipation in the metal. In principle, the propagation losses of surface plasmon-polaritons can be compensated through optical amplification. The objective of this thesis is to provide deeper insights on the physics of surface plasmon-polariton amplification and spontaneous emission in surface plasmon-polariton amplifiers through theoretical and experimental vehicles applied (but not necessarily restricted) to a particular plasmonic mode termed long-range surface plasmon-polariton. On the theoretical side, the objective is approached by developing a realistic theoretical model to describe the small-signal amplification of surface plasmon-polaritons in planar structures incorporating dipolar gain media such as organic dye molecules, rare-earth ions, and quantum dots. This model takes into account the inhomogeneous gain distribution formed near the metal surface due to a non-uniform excitation of dipoles and due to a position-dependent excited-state dipole lifetime that results from near-field interactions between the excited dipoles and the metal. Also, a theoretical model to describe the amplified spontaneous emission of surface plasmon-polaritons supported by planar metallic structures is developed. This model takes into account the different energy decay channels into which an exited dipole located in the vicinity of the metal can relax. The validity of this model is confirmed through experimentation. On the experimental side, the objective is approached by providing a direct experimental demonstration of complete loss compensation in a plasmonic waveguide. The experiments are conducted using the long-range surface plasmon-polariton supported by a symmetric thin gold waveguide incorporating optically pumped organic dye molecules in solution as the gain medium. Also, an experimental study of spontaneous emission in a long-range surface plasmon-polariton amplifier is presented. It is shown that this amplifier benefits from a low spontaneous emission into the amplified mode, which leads to an optical amplifier with low noise characteristics. The experimental setup and techniques are explained in detail.

Les rétrovirus murins peuvent causer une grande incidence de leucémies par le processus de mutagenèse insertionelle. L'intégration d'un rétrovirus au niveau du même locus dans plus d'une tumeur définit un site commun d'intégration (CIS). L'identification des nouveaux sites communs d'intégration rétrovirale s'avère un outil important pour identifier de nouveaux gènes pouvant être impliqués dans l'apparition primaire du cancer chez l'être humain. Nous avons adapté une nouvelle technique pour isoler rapidement des sites d'intégration rétrovirale. Cette technique, appelée PCR-splinkerette, permet de mettre en évidence un grand nombre de ces sites et de trouver des nouveaux gènes impliqués dans les leucémies murines causées par le rétrovirus Graffi 1.4. En utilisant cette méthode, il nous a été possible de situer plusieurs intégrations du rétrovirus dans le génome de la souris et de repérer les gènes à proximité de l'intégration, à l'aide de banques de données (ENSEMBL). Nous avons cloné et analysé les séquences de 63 sites d'intégration rétrovirale (RISs) à partir de 12 tumeurs composées par des lymphomes de cellules T, B, myéloïdes, érythrocytaires et mégacaryocytaires, induits par Graffi 1.4. Les gènes Notch1, Ras Grp1, Myc, Ptpn6, Gse1, Lmo2 et Evi1 et Prdm16 dont le rôle est déjà connu dans le cancer, ont été trouvés à proximité de ces sites. Trois régions susceptibles de posséder plus d'une intégration dans le même locus, ont été identifiées sur les chromosomes 17D, 14B, 4E1. Plusieurs gènes trouvés autour de ces régions n'ont pas été rapportés comme étant des oncogènes connus. Une analyse plus profonde de ces sites et des gènes dont l'expression est modifiée dans ces tumeurs permettrait de mieux comprendre les mécanismes impliqués dans le développement du cancer. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Rétrovirus, Rétrovirus Graffi 1.4, Leucémie, Mutagenèse insertionelle, Réaction en chaîne de la polymérase, Splinkerette, Oncogènes, Gènes suppresseurs de tumeurs.

The in situ proximity ligation assay (in situ PLA) is an immunoassay that enables directvisualisation of single protein targets or protein interactions in cell or tissue samples. This project revolves around designing and introducing several novel multiplexable components tobe used in conjunction with Olink Bioscience's Duolink product line. In this report, a novel in silico approach to DNA oligomer interaction design is presented. Using this in silico method, a multiplexed system of DNA oligomers has been designed andevaluated using in situ PLA and fluorescence microscopy.