Cette thèse de doctorat s'inscrit dans le cadre de projets CRIAQ (Consortium de recherche et d'innovation en aérospatiale du Québec) orientés vers le développement d'approches embarquées pour la détection de défauts dans des structures aéronautiques. L'originalité de cette thèse repose sur le développement et la validation d'une nouvelle méthode de détection, quantification et localisation d'une entaille dans une structure de joint à recouvrement par la propagation d'ondes vibratoires. La première partie expose l'état des connaissances sur l'identification d'un défaut dans le contexte du Structural Health Monitoring (SHM), ainsi que la modélisation de joint à recouvrements. Le chapitre 3 développe le modèle de propagation d'onde d'un joint à recouvrement endommagé par une entaille pour une onde de flexion dans la plage des moyennes fréquences (10-50 kHz). À cette fin, un modèle de transmission de ligne (TLM) est réalisé pour représenter un joint unidimensionnel (1D). Ce modèle 1D est ensuite adapté à un joint bi-dimensionnel (2D) en faisant l'hypothèse d'un front d'onde plan incident et perpendiculaire au joint. Une méthode d'identification paramétrique est ensuite développée pour permettre à la fois la calibration du modèle du joint à recouvrement sain, la détection puis la caractérisation de l'entaille située sur le joint.Cette méthode est couplée à un algorithme qui permet une recherche exhaustive de tout l'espace paramétrique.Cette technique permet d'extraire une zone d'incertitude reliée aux paramètres du modèle optimal. Une étude de sensibilité est également réalisée sur l'identification. Plusieurs résultats de mesure sur des joints à recouvrements 1D et 2D sont réalisées permettant ainsi l'étude de la répétabilité des résultats et la variabilité de différents cas d'endommagement. Les résultats de cette étude démontrent d'abord que la méthode de détection proposée est très efficace et permet de suivre la progression d'endommagement. De très bons résultats de quantification et de localisation d'entailles ont été obtenus dans les divers joints testés (1D et 2D). Il est prévu que l'utilisation d'ondes de Lamb permettraient d'étendre la plage de validité de la méthode pour de plus petits dommages. Ces travaux visent d'abord la surveillance in-situ des structures de joint à recouvrements, mais d'autres types de défauts. (comme les disbond) et. de structures complexes sont également envisageables.

Le cœur est un organe central au fonctionnement du système cardiovasculaire. Il est physiologiquement compartimenté et est constitué de cellules spécialisées qui régulent les impulsions électriques ainsi que la contraction du myocarde. Le cœur adapte le flux sanguin en fonction des besoins du corps. En condition pathologique, le cœur recourt toutefois à des mécanismes compensatoires. Au niveau physiologique, la compensation s’observe par l’hypertrophie des cardiomyocytes qui, bien que bénéfique à court terme, exacerbe à long terme la fonction cardiaque. L’activation des « mitogen activated protein kinases » (MAPK) contribue autant au maintien de la fonction physiologique qu’à la détérioration pathologique du myocarde et serait également une cause de l’hypertrophie observée. Parmi les 5 groupes de MAPK connues, la MAPK p38 est formée de 4 isoformes dont les sérine/thréonine kinases p38α et p38γ sont exprimées de façon prédominante dans le cœur. Les p38 partagent les mêmes activateurs, mais leurs effecteurs diffèrent. Bien que le rôle de p38α semble impliqué dans l’aggravement des troubles cardiaques, celui de p38γ ne semble pas redondant à p38α et demeure incompris. Cette isoforme possède un motif de liaison aux domaines PDZ, unique chez les MAP kinases. Également, chez les cellules cardiaques, elle transloque au noyau en condition de stress. Le but de l’étude ici est de comprendre le rôle de p38γ et de ses motifs uniques sur la structure et la taille des cardiomyocytes. Afin de répondre au but de l’étude, plusieurs mutants adénoviraux de p38 ont été conçus. Un des mutants ne possède pas le motif de liaison aux domaines PDZ, deux autres contrôlent la localisation cellulaire soit au noyau, soit au cytoplasme, et un autre mutant est muté au site de phosphorylation. Des cardiomyocytes en culture ont été infectés par les différents mutants en présence de leur activateur en amont ou de la β-galactosidase. Les réseaux d’α-actinine, ainsi que la taille des cardiomyocytes, ont été observés par microscopie. Les observations effectuées montrent que p38γ entraîne une désorganisation des réseaux d’α-actinine lorsqu’il est phosphorylé. Également, il facilite l’hypertrophie des cardiomyocytes en présence de son activateur s’il est forcé hors du noyau ou en l’absence de son motif de liaison aux domaines PDZ. En conclusion, les résultats obtenus suggèrent que p38γ exerce bel et bien un rôle dans le maintien structural des cardiomyocytes par l’intermédiaire de l’α-actinine.

The rock paintings of the hunter-gatherers in the province of Norrland, and their localisation. The aim of this thesis is to find a couple of distinguishing features for the localisation of the rock paintings of the hunter-gatherers in Norrland. This will be done through studies of Swedish and international literature, about ancient rock-art and the belief system of the hunter-gatherers. I will make comparisons  with other groups of hunter-gatherers and try to find analogies. My belief is that there must be a large number of undetected rock paintings in Norrland. They are hard to find because of overgrowth by lichen and damages due to wethering. Theretoo I feel that there hasn´t been enough of structured surveys. I hope that my resulting short list of practical clues of where to find them will help: seek for them in the boreal forest area from 200 meters above the sea level to the present alpine tree line zone in close vicinity to neolithic winter dwellings in close vicinity to pitfall traps on vertical rock walls of cliffs or boulders in close vicinity to standing water/ alternatively in a hillside in the forest the rock faces to the south on imposing natural formations try to find them in cloudy, humid weather

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Background HER2-positive breast cancer is a poor prognostic subgroup, even if treated with anti-HER2 directed therapy. Trastuzumab is an important HER2-targeting antibody but only limited patients respond to this drug, and acquired resistance is a common problem. HER3 has been shown to be a key candidate in mediating resistance to trastuzumab and other ErbB inhibitors. The aims of the project are to investigate the resistance mechanisms and the relevant biomarkers in relation to trastuzumab treatment and resistance in HER2-positive breast cancer, in particular, HER3 subcellular localisation and HER3 phosphorylation. Methods Effects of trastuzumab on HER3 subcellular localisation and HER3 phosphorylation in relation to MET receptor were studied using western blots, nuclear fractionation, confocal microscopy, and immunoprecipitation in a panel of HER2-positive cell lines, including SKBr3 and BT474 breast cancer cells in which trastuzumab resistance was induced by long-term drug exposure. Effects of drug and knockdown experiments were tested by cell viability and proliferation assays. HER3 and MET expression was assessed by immunohistochemistry in xenograft tumours and human tissue samples, and clinical impact was assessed in different cohorts of HER2-positive breast cancer patients. Results Acquired trastuzumab resistant SKBr3 cells showed an increase of nuclear HER3_100kD, which was derived from C-terminus of HER3. Nuclear HER3_100kD could be due to the proteolytic cleavage of HER3 since it was reduced by ADAM17 or gamma-secretase inhibitor. In a panel of HER2-positive cell lines and xenograft samples, nuclear HER3 was observed only in the resistant cells. In addition, nuclear HER3 was associated with poor progression-free and overall survivals in HER2-positive breast cancer patients. It was also found that HER3 phosphorylation was maintained in acquired trastuzumab resistant cells, which was contributed by the ligand independent interaction of MET and HER3. Higher MET expression was associated with better overall survival in HER2-positive, breast cancer patients who were not treated with trastuzumab. Conclusions Nuclear HER3 was found in trastuzumab resistant cells and appeared to result from HER3 proteolytic cleavage mediated by ADAM17 and gamma-secretase. Further studies are required to investigate its mechanism and to identify the HER3 cleavage sites. MET was a key factor in maintaining HER3 phosphorylation during trastuzumab resistance. Lastly, nuclear HER3 and MET could be two potential biomarkers in HER2-positive breast cancer.

L'objectif de cette étude est de comprendre la localisation des entreprises européennes et chinoises dans le cadre de la mondialisation. La recherche est fondée sur trois parties principales : a) l'apport théorique aux échanges commerciaux, à l'IDE et à la mondialisation ; b)les déterminants principaux de délocalisation et localisation entre entreprises européennes et chinoises ; c) les activités des entreprises délocalisées et les conséquences provoquées dans les pays d'accueil et les pays d'origine. Les entreprises européennes, délocalisées et localisées en Chine sont généralement attirées par les avantages de ce pays que sont le faible coût de main-d'oeuvre et une immense demande intérieure. Les entreprises chinoises, elles, s'intéressent à racheter les entreprises européennes puisqu'elles peuvent maîtriser rapidement la technologie avancée, les grandes marques et le réseau de la distribution. La Chine a bénéficié de l'implantation des entreprises européennes, mais elle a rencontré également des problèmes sérieux. Dans les pays européens, la délocalisation des entreprises vers la Chine est à l'origine de problèmes importants comme la baisse des emplois industriels. L'arrivée des entreprises chinoises ne jouera pas un rôle important en matière de création des emplois et de réduction du déficit du côté de l'Union. Les défis et les obstacles rencontrés dans les pays d'accueil peuvent donc amener les entreprises à réfléchir sur leurs stratégies de localisation. / The objective of this work is to understand the localization of the European and the Chinese enterprises within the framework of globalization; The research is founded on three principal parts : a) the theoretical contribution with trade, IDE and globalization ; b) the principal determinants of offsourcing and localization between the European and the Chinese enterprises ; c) the activities of the enterprises localized and the consequences caused in the host countries and the countries of origin. The european enterprises, localized in China are generally attracted by the comparative advantages of this country like the low cost of labour and an immense domestic demand. The Chinese enterprises are interested to purchase the European enterprises since they could quickly control the leading-edge technology, the famous brands and the distribution network. China profited a lot from the localization of the European enterprises (the progression of technology), but it also encounters serious problems (the shortage of the raw materials). In the european countries, the localization of the enterprises in the foreign countries caused some problems such as the fall of industrial employment. Moreover, the arrival of the chinese enterprises cannot play an important role as regards creation of employment and reduction of the deficit on the side of the European Union. In conclusion, the challenges and the obstacles met in the host countries can leave the European and the Chinese enterprises to think about their strategies of localization.

Offshore software development (OSD) is a leading business sector in the present ‘glocal’ IT marketplace, and vendors in different countries are opening software development centres worldwide to take advantage of the new business opportunities. However, software development is both a technical and a social process as various software modules need to be integrated, which requires ongoing interaction between the stakeholders. The software modules rely upon local knowledge regarding customer wants, project specific features, chosen design methodologies by development team members and synchronisation of activities to confirm the next design iteration. This study focuses on knowledge sharing processes involving the interplay between acquiring local knowledge and applying the knowledge acquired into the design of the client-specific software builds. New knowledge is created as new processes are applied and new outcomes realised, resulting in re-definition of software development practices. Building on existing theories with empirical case study evidence, this research reveals the socio-technical influences on knowledge management in the OSD process. Ideographic research methods have been applied to bring sensitivity in the everyday organisational activities for knowledge sharing across diverse social and cultural groups within two country contexts (New Zealand and India). Empirical data from ten case studies is used to inductively develop a conceptual framework, which has been applied to make within case and cross case comparisons across three levels of analysis (micro, meso and macro) for knowledge sharing. The micro level analysis explores individual key success drivers (behaviours and methodologies), the meso level explores organisational level practices (work processes and structures) and the macro level gives a holistic evaluation across two country contexts. Country contexts reveal that New Zealand vendors share closer cultural proximity with their clients, are engaged in client facing skills and have further outsourced software development tasks to other low cost countries. The Indian vendors are involved in software construction, prefer technical specialist skills and have defined more discipline in their software development processes. The thesis offers new insights on how vendors’ shape their software development styles based upon their beliefs and understanding of the offshore market and is especially relevant to both vendors and clients who intend venturing into the offshore market.

Doctor of Philosophy (PhD) / This thesis addresses the issues arising in range-only localisation and tracking using Radio Frequency Received Signal Strength Indicator measurements. One of the key issues in Radio Frequency (RF) based localisation and tracking applications is to obtain an accurate sensor representation. Such a sensor model is one of the prerequisites to achieve high accuracy and precision in the localisation and tracking task. The sensor models used at present for this task are very simplistic, and as a consequence are unable to achieve highly accurate and precise localisation. While such an accurate sensor description is desirable it has not been presented for RF sensors. This thesis addresses the task of obtaining an accurate sensor model for RF sensors. The major drawbacks of the most commonly used model, the nth power model, are demonstrated. A new model to satisfy the necessary requirements for high accuracy localisation is developed. This model is based on theoretical considerations and experimental data. It depicts the real occurring behaviour of RF sensors more closely than the models used so far for RF based range-only localisation. The use of this better sensor representation offers the possibility of achieving more accurate localisation. The expected performance of the alternative sensor model is compared to the commonly used nth power model. Furthermore, the inherent properties of the new sensor model are presented and their ramifications with regards to the goal of achieving highly accurate localisation are discussed. In addition to the sensor model development, the well-known probabilistic filtering techniques Kalman Filter, Particle Filter and Histogram Filter are compared and used to implement 1-dimensional and 2-dimensional range-only trackers. The filtering techniques are evaluated with respect to their suitability for appropriately handling the new multi-modal sensor model and the resulting multi-modal state distributions, and to provide correct and conclusive localisation and tracking results. Results from experiments using real data obtained in outdoor environments with a prototype RF localisation system as well as results obtained from simulations are presented in this thesis to validate the theoretical findings and the newly developed sensor model.

This thesis deals with the Simultaneous Localisation and Mapping algorithm as it pertains to the deployment of mobile systems in unknown environments. Simultaneous Localisation and Mapping (SLAM) as defined in this thesis is the process of concurrently building up a map of the environment and using this map to obtain improved estimates of the location of the vehicle. In essence, the vehicle relies on its ability to extract useful navigation information from the data returned by its sensors. The vehicle typically starts at an unknown location with no a priori knowledge of landmark locations. From relative observations of landmarks, it simultaneously computes an estimate of vehicle location and an estimate of landmark locations. While continuing in motion, the vehicle builds a complete map of landmarks and uses these to provide continuous estimates of the vehicle location. The potential for this type of navigation system for autonomous systems operating in unknown environments is enormous. One significant obstacle on the road to the implementation and deployment of large scale SLAM algorithms is the computational effort required to maintain the correlation information between features in the map and between the features and the vehicle. Performing the update of the covariance matrix is of O(n�) for a straightforward implementation of the Kalman Filter. In the case of the SLAM algorithm, this complexity can be reduced to O(n�) given the sparse nature of typical observations. Even so, this implies that the computational effort will grow with the square of the number of features maintained in the map. For maps containing more than a few tens of features, this computational burden will quickly make the update intractable - especially if the observation rates are high. An effective map-management technique is therefore required in order to help manage this complexity. The major contributions of this thesis arise from the formulation of a new approach to the mapping of terrain features that provides improved computational efficiency in the SLAM algorithm. Rather than incorporating every observation directly into the global map of the environment, the Constrained Local Submap Filter (CLSF) relies on creating an independent, local submap of the features in the immediate vicinity of the vehicle. This local submap is then periodically fused into the global map of the environment. This representation is shown to reduce the computational complexity of maintaining the global map estimates as well as improving the data association process by allowing the association decisions to be deferred until an improved local picture of the environment is available. This approach also lends itself well to three natural extensions to the representation that are also outlined in the thesis. These include the prospect of deploying multi-vehicle SLAM, the Constrained Relative Submap Filter and a novel feature initialisation technique. Results of this work are presented both in simulation and using real data collected during deployment of a submersible vehicle equipped with scanning sonar.

Thèse de doctorat : Neurosciences : Strasbourg 1 : 2008. / Extrait en partie de périodique. Titre provenant de l'écran-titre. Bibliogr. p. 147-161.