Des nanobâtonnets de trioxyde de tungstène peuvent être élaborés sur un substrat de mica de type muscovite à l'aide d'une méthode simple de dépôt en phase vapeur. La croissance de ces objets semble obéir à un mode de croissance de type Stranski-Krastanov. Les nanobâtonnets sont majoritairement constitués d'une phase hexagonale métastable qui a été mise en évidence par MET. Cette structure se forme à partir d'un bronze de tungstène interfacial de structure hexagonale, qui croît en épitaxie sur le mica. Ce bronze contient du potassium provenant du substrat. Pour les bâtonnets les plus épais, la phase hexagonale est surmontée d'une structure monoclinique. La stabilité thermique de la structure hexagonale est importante puisqu'après un recuit à 600°C cette phase subsiste alors que la morphologie en bâtonnets est détruite. Les processus stabilisants la structure hexagonale sont apparemment à dissocier de ceux conduisant à la morphologie en bâtonnets. Le potassium joue un rôle majeur lors de la croissance des nanobâtonnets de WO3. Des élaborations de nanophases d'oxyde de tungstène suivies in situ par photoémission ainsi que par EXAFS de surface sur des substrats volontairement dopés avec du potassium mettent en évidence la forte affinité de cet élément avec le tungstène. Celle-ci peut même entraîner la décomposition partielle d'une molécule telle que du carbonyle de tungstène juste physisorbée à température cryogénique. En outre, la présence du potassium conduit à des phases plus oxydées qu'en son absence.

The ability of human polymorphonuclear leukocytes (PMNL; neutrophils), to sense and move to sites of infection is essential for our defense against pathogens. Cell motility is critically dependent on a dynamic remodeling of morphology. The morphological polarization toward chemoattractants, such as N-formyl-Met-Leu-Phe (fMLF), is associated with temporary extension and stabilization of lamellipodia in the direction of movement. The underlying mechanisms of cell motility are, however, still not entirely elucidated. It is therefore an urgent task to extend the present experimental evidence to give solid basis for a comprehensive model. Here it is shown that nitric oxide (NO) stimulates the morphological response of neutrophils, most likely due to transient increases in [Ca2+]i, following addition of NO-donors. This will, hypothetically, activate gelsolin and other actin filament severing proteins, leading to a subsequent decrease in filamentous actin. The incapability to efficiently turnover the actin filament network then blocks all motile activity. It is also shown that N-formyl peptide receptors on polarized neutrophils accumulate non-uniformly towards regions involved in motility. It is suggested that neutrophils use the asymmetric receptor distribution for directional sensing and sustained migration. A model for lamellipodium extension, where water fluxes play a pivotal role is presented. It is suggested that water fluxes through water-selective aquaporin (AQP) channels, contribute to the propulsive force for formation of various membrane protrusions and, thus, cell motility. It is well known that small G proteins of the Rho family GTPases play important roles in the intracellular signaling underlying cell motility. In morphologically polarized neutrophils it is shown that Cdc42, Rac2 and RhoA display spatially distinct distributions, which allows for sequential chemoattractant stimulation of neutrophil motility. The specific localizations of Rac2, Cdc42 and RhoA relative to each other and filamentous actin and fMLF receptors support the hypothesized order of activation and regulation of neutrophil cell motility. In conclusion, the detailed analysis of motility-related issues presented here provide new data allowing further refinement of previous models of neutrophil motility.

The urban near surface atmosphere is of great concern since it affects the climate to which an increasing amount of people are immediately exposed. This study investigated the microclimate in central Stockholm in terms of the thermal conditions in the 0-2.5 m air layer and the water and heat exchange processes at different types of surfaces found within the urban environment. The main objective was to improve our understanding of the urban small-scale climate system. The urban microclimate was measured in terms of vertical air temperature profiles along a horizontal transect running through a vegetated park and its built-up surroundings during three clear and relatively calm summer days. The results showed that the air temperature at 1.2 m height within the park was 0.5 to 1.5 K lower than in the surrounding city blocks, and that the thermal stratification was generally stable (increasing temperature with height) in the park and unstable (decreasing temperature with height) in the built-up areas. In addition, there were a few examples of temperature gradients orientated in different directions within the lowest 2.5 m air layer, indicating horizontal advection between the park and the built-up areas. Climate conditions simulated with a three-dimensional microclimate model agreed well with observations and the model was therefore assumed to provide reasonable representations of important climate processes such as surface-air energy exchange processes. However, there were some discrepancies between observations and simulations that are discussed in terms of differences in real and modelled heat storage processes and wind conditions. Processes that need to be included for a more precise model description of areas such as the Stockholm environment include dynamic heat storage in buildings and dynamic wind forcing during the course of the simulation. A soil-vegetation-atmosphere transfer model was used to study soil water transport, the surface energy balance of an asphalt surface, and the impact of urban climate on evapotranspiration. Based on model calibration to field measurements of soil water content in a till catchment outside Stockholm, new parameter values were estimated that can be used for water flow modelling of till soils. The heat fluxes of an asphalt surface were reliably simulated without knowledge of site-specific calibration and the model was useful in identifying problems with energy balance closure based on measurements only. Simulations of ‘urban’ modifications to the forcing climate conditions demonstrated that increased air temperature, and thereby increased vapour pressure deficit, had most effect on evapotranspiration from tall vegetation, while increased long-wave radiation raised grass evapotranspiration the most. / QC 20100901

Ce travail de thèse s'est focalisé sur l'étude des alliages Fe-14%Cr nanorenforcés par dispersion d'oxydes obtenus par broyage à haute énergie à partir de poudres pré-alliées de la matrice et d'Y2O3. L'objectif était double : (i) étudier la cinétique de précipitation, en particulier la phase de coalescence, des oxydes en fonction de la teneur en élément d'addition (Ti, Y, O) lors de traitements thermiques à haute température et postérieurs à l'étape de consolidation, et (ii) d'analyser les hétérogénéités de déformations élastiques et élastoplastiques dans ces aciers en fonction de l'avancement de la précipitation. La microstructure et la nanostructure ont été étudiées par microscopie électronique en transmission (MET) et diffusion de neutrons aux petits angles (DNPA). L'ensemble de ces techniques a permis de mettre en évidence des comportements différents selon les teneurs en éléments d'addition. En particulier, l'ajout de titane induit un ralentissement très net de la coalescence des particules contrairement aux ajouts d'oxygène et d'yttrium. Ces variations de teneurs initiales influent sur la forme, la structure cristallographique des particules, sur les relations d'orientations avec la matrice et en voie de conséquence, sur les cinétiques de précipitation. Par conséquent, assurer un rapport Ti /Y supérieur à 1 et limiter l'apport en oxygène sont des garants de la stabilité des nanoparticules à hautes températures dans les aciers ODS. Le phénomène de recristallisation a également été observé à haute température dans les matériaux dans lesquels la coalescence des oxydes est largement avancée. Afin de corréler l'évolution des microstructures avec celle des propriétés mécaniques, une modélisation macroscopique du durcissement a ensuite été réalisée, en distinguant les différentes contributions (nanoparticules, taille de grains et dislocations). Le durcissement calculé à partir des observations expérimentales est en très bon accord avec les valeurs mesurées. Ces calculs rendent bien compte des variations entre alliages et mettent en évidence l'influence prépondérante de la taille des particules sur la dureté des matériaux. Enfin une étude fine des hétérogénéités de déformation des grains en fonction de leur orientation cristallographique a été menée par diffraction de neutrons. Ces résultats ont été confrontés à un calcul micromécanique en champ moyen. Cette dernière partie a montré l'existence de comportements locaux différents dans des matériaux présentant des comportements macroscopiques similaires.

Radioresistance is a major cause of treatment failure and relapse in head and neck squamous cell carcinoma (HNSCC). Novel molecular targets need to be identified to increase cure rates and radiosensitivity in HNSCC. The MET receptor tyrosine kinase is highly dysregulated in cancer and plays a role in tumourigenesis, chemoresistance, and radioresistance. However, the role of MET in HNSCC radioresistance has not yet been investigated and may potentially be a radiosensitizing target. We discovered MET expression and intact ligand-induced signalling in HNSCC cell lines. Small molecule MET kinase inhibitors inhibited ligand-induced MET activation and downstream signalling. These inhibitors decreased HNSCC cell proliferation and clonogenic survival. Similarly, short-interfering RNAs targeting MET also decreased cell proliferation. The combination of radiation with the MET kinase inhibitors decreased clonogenic survival in an additive manner. Cell cycle analyses demonstrated that MET inhibitors alone or in combination with radiation induced small increases in sub-G1 cell populations.

Radioresistance is a major cause of treatment failure and relapse in head and neck squamous cell carcinoma (HNSCC). Novel molecular targets need to be identified to increase cure rates and radiosensitivity in HNSCC. The MET receptor tyrosine kinase is highly dysregulated in cancer and plays a role in tumourigenesis, chemoresistance, and radioresistance. However, the role of MET in HNSCC radioresistance has not yet been investigated and may potentially be a radiosensitizing target. We discovered MET expression and intact ligand-induced signalling in HNSCC cell lines. Small molecule MET kinase inhibitors inhibited ligand-induced MET activation and downstream signalling. These inhibitors decreased HNSCC cell proliferation and clonogenic survival. Similarly, short-interfering RNAs targeting MET also decreased cell proliferation. The combination of radiation with the MET kinase inhibitors decreased clonogenic survival in an additive manner. Cell cycle analyses demonstrated that MET inhibitors alone or in combination with radiation induced small increases in sub-G1 cell populations.

We consider three distinct categories of supersymmetric scenarios with heavy scalars and light gauginos. First, we investigate the SO(10) SUSY GUTs, and locate MSSM parameter space regions that satisfy GUT scale Yukawa unification, which is a distinct feature of these models. Then taking example SO(10) cases, we perform a Monte Carlo study with toy detector simulation at 14 TeV at the LHC on the no $met$ leptonic channels 2,3 leptons + $ge$4 jets and show that discovery is possible with $sim$1 fb$^{-1}$ of integrated luminosity. We also demonstrate the feasibility of invariant mass endpoint measurements for $sim$100 fb$^{-1}$. Furthermore, in a cosmological context, we propose that SO(10) scenarios with excess neutralino relic abundance can be made WMAP-compatble by assuming neutralino decays to axinos, and show that there are various axino/axion cold and warm dark matter admixtures which can be consistent with non-thermal leptogenesis requirements for the thermal re-heat temperature. Afterwards we complement the SO(10)s with the string-inspired G$_2$-MSSM and focus point mSUGRA scenarios and perform a full simulation search of these at $sqrt{s} =$ 14 TeV at the LHC with the CMS detector where the main production mechanism is through gluino pair production and the final states are cheracterized by all-hadronic topologies (including $b$s and $t$s). Through the design of six prototype all-hadronic selection paths and using the CMS High Lever Trigger paths with highest significance (including the $b$-enriched ones), we find that all but one model benchmarks are accessible with 100 pb$^{-1}$ integrated luminosity. We present the results as a function of the gluino mass considering the major detector systematic effects.

Les tokamaks sont les machines d'étude en vue de produire de l'énergie par fusion contrôlée de deux noyaux isotopes de l'hydrogène dans un plasma chaud confiné magnétiquement. Un des problèmes est celui de l'interaction plasma-paroi. L'élément principal composant les parois soumises aux plus forts flux est le carbone qui donnent lieu à des phénomènes complexes d'érosion. Ceci provoque la formation de dépôts ou de poussières qui sont potentiellement réactives en cas d'ouverture accidentelle de la machine. Un autre inconvénient est que ces dépôts contiennent du deutérium et potentiellement du tritium pour ITER. Cette rétention du combustible extrapolée à ITER est critique. Dans le but d'éclaircir le rôle des dépôts dans la rétention, nous avons caractérisé par différentes méthodes complémentaires les échantillons prélevés à des endroits similaires (neutraliseurs) de deux tokamaks : Tore Supra (France) et TEXTOR (Allemagne). Les volumes poreux accessibles et la distribution de taille des pores de ces dépôts sont déterminés par l'analyse d'isothermes d'adsorption de méthane et d'azote par les méthodes BET, Dubinin-Radushkevich, $\alpha$s et la théorie de la fonctionnelle de la densité (DFT). Afin de tenter de comprendre les mécanismes de croissance, nous avons également étudié la structure globale des dépôts. Nous montrons par Microscopie Electronique à Transmission (MET) et microspectrométrie Raman qu'ils sont non amorphes mais néanmoins très désordonnés. Nous avons également montré la présence de nanoparticules (4 à 70 nm de diamètre). Nous montrons que les nanoparticules sont comparables aux noirs de carbone : les nanoparticules sont donc sans doute formées en phase homogène dans le plasma de bord. Nous mettons alors en évidence un double processus de croissance : homogène et hétérogène.

Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by the ectopic expression of defined factors. iPSCs hold great promise for pharmaceutical screening and regenerative medicine but the mechanism of reprogramming is not well understood. This work examines a component process of reprogramming that is the mesenchymal-to-epithelial transition (MET), an important step in the generation of iPS cells. In this thesis I demonstrate a connection between BMP signaling and the reprogramming factor Klf4 in the activation of the MET expression program. Using ChIP-Seq I mapped the binding of Klf4 and BMP Smads across the genome and linked their co-binding to a MET expression program determined by RNA-Seq. My work uncovers a thus-far unreported interaction between Klf4 and BMP signaling in cellular epithelialization that can directly improve the technical methods of reprogramming and have important implications for the induction of epithelial tissues in general.

Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by the ectopic expression of defined factors. iPSCs hold great promise for pharmaceutical screening and regenerative medicine but the mechanism of reprogramming is not well understood. This work examines a component process of reprogramming that is the mesenchymal-to-epithelial transition (MET), an important step in the generation of iPS cells. In this thesis I demonstrate a connection between BMP signaling and the reprogramming factor Klf4 in the activation of the MET expression program. Using ChIP-Seq I mapped the binding of Klf4 and BMP Smads across the genome and linked their co-binding to a MET expression program determined by RNA-Seq. My work uncovers a thus-far unreported interaction between Klf4 and BMP signaling in cellular epithelialization that can directly improve the technical methods of reprogramming and have important implications for the induction of epithelial tissues in general.