In a growing number of cutting edge centres around the world, radiotherapy treatments delivered by beams of protons and carbon ions offer the opportunity to target tumours with unprecedented conformality. But a sharper dose distribution increases the need for efficient quality control. Treatments are still affected by uncertainties on the penetration depth of the beam within the patient, requiring medical physicists to add safety margins. To reduce these margins and deliver safer treatments, different projects investigate real time range control by imaging prompt gammas emitted along the proton or carbon ion tracks in the patient.<p><p>This thesis reports on the feasibility, development and test of a new type of prompt gamma camera for proton therapy. This concept uses a knife-edge slit collimator to obtain a 1-dimensional projection of the beam path on a gamma camera. It was optimized, using the Monte Carlo code MCNPX version 2.5.0, to select high energy photons correlated with the beam range and detect them with both high counting statistics and sufficient spatial resolution for use in clinical routine. To validate the Monte Carlo model, spectrometry measurements of secondary particles emitted by a PMMA target during proton irradiation at 160 MeV were realised. An excellent agreement with the simulations was observed when using subtraction methods to isolate the gammas in direct incidence. A first prototype slit camera using the HiCam gamma detector was consequently prepared and tested successfully at 100 and 160 MeV beam energies. If we neglect electronic dead times and rejection of detected events, the current solution with its collimator at 15 cm from beam axis can achieve a 1-2 mm standard deviation on range estimation in a homogeneous PMMA target for numbers of protons that correspond to doses in water at Bragg peak as low as 15 cGy at 100 MeV and 25 cGy at 160 MeV assuming pencil beams with a Gaussian profile of 5 mm sigma at target entrance.<p><p>This thesis also investigates the applicability of the slit camera for carbon ion therapy. On the basis of Monte Carlo simulations with the code MCNPX version 2.7.E, this type of camera appears not to be able to identify the beam range with the required sensitivity. The feasibility of prompt gamma imaging itself seems questionable at high beam energies given the weak correlation of secondaries leaving the patient.<p><p>This work consequently concludes to the relevance of the slit camera approach for real time range monitoring in proton therapy, but not in carbon ion therapy. / Doctorat en Sciences de l'ingénieur / info:eu-repo/semantics/nonPublished

The dissertation describes the method of inserting polar-axis system into the video recording of cataract operation at the Geminy Eye Surgery, Zlin. At the theoretical part, it discusses requirements for inserting the polar-axis system including elimination of eye rotary movements captured by slit lamp. Then the emphasis is also on the speed of data processing. The practical part of the dissertation, focuses on the creating the method for detection of centers at the slit lamp picture, as well as video sequence and a method that eliminates potential eye rotation. For designing the program solution, following methods were used: Otsu method, Hough transformation method, method of two vertical projections, and crosscorrelation method. In total, the program solution was tested and analyzed in Matlab program on anonymous data set of 22 eyes.

Collective cell migration is a defining feature of many morphogenetic processes. Diseases such as congenital heart diseases and cancer arise due to mis-regulation of collective migratory behaviour and animal models have played a pivotal role in dissecting the molecular mechanisms which underlie this process. During embryonic heart development, cardiac precursors undergo a stage of collective migration in both vertebrates and invertebrates. We developed a paradigm to quantitatively assess collective cell migration of cardiac precursors in live embryos of Drosophila, which is the simplest genetic model organism with a heart. Therefore, we studied processes which are commonly observed in most collective cell migration models such as guidance signalling and extracellular matrix remodelling. Our results demonstrate that leading edge of migrating cardioblasts is highly active and that this behaviour is regulated by guidance cues, Slit and Netrin and their respective receptors Robo/Robo2 and Frazzled/Uncoordinated5. These molecules cooperatively promote leading edge motility and epithelial characteristics of the cardioblasts. Next, we determined that matrix restructuring around the cardioblasts requires proteases Mmp1 and Mmp2, which are members of the highly conserved Matrix Metalloproteinase family. We demonstrate that Mmp1 and Mmp2 have distinct roles during lumen formation, however, both Mmp1 and Mmp2 are required for collective motility of the cardioblast leading edge. Hence, we propose that embryonic heart development in Drosophila is an effective and amenable model of collective cell migration which can be applied to discover unique mechanisms which coordinate cell movement in groups. / Thesis / Doctor of Philosophy (PhD)

Pour la première fois, en associant un microscope à effet tunnel (STM) et un microscope optique inversé,nous avons imagé les plasmons de surface excités électriquement sur un film d’or avec la pointe d’un STM.Par microscopie de fuite radiative, en observant l’image de l’interface air/or et celle du plan de Fourierassocié, nous avons distingué les plasmons propagatifs des plasmons localisés sous la pointe. Les plasmonspropagatifs sont caractérisés par une distance de propagation et une direction d’émission en accord aveccelles de plasmons propagatifs créés par excitation laser sur des films d’or de mêmes épaisseurs. Les fuitesradiatives des plasmons localisés s’étalent jusqu’à l’angle maximum d’observation. Plasmons propagatifs etlocalisés ont une large bande spectrale dans le visible. Si la pointe est plasmonique (en argent), lesplasmons localisés ont une composante supplémentaire due au couplage associé. Pour différents types depointe, nous avons déterminé les intensités relatives des plasmons localisés et propagatifs. Nous trouvonsque chaque mode plasmon (propagatif ou localisé) peut être préférentiellement sélectionné en modifiant lematériau de la pointe et sa forme. Une pointe en argent produit une intensité élevée de plasmons localisés,tandis qu’une pointe fine de tungstène (rayon de l’apex inférieur à 100 nm) produit essentiellement desplasmons propagatifs. Nous avons étudié la cohérence spatiale des plasmons propagatifs excités par la pointe du STM. Avec un film d’or opaque (épaisseur 200 nm) percé de paires de nanotrous nous avons réalisé une expérienceanalogue à celle des fentes d’Young. Des franges d’interférences sont observées. La mesure de leurvisibilité en fonction de la distance des nanotrous donne une longueur de cohérence des plasmons de 4.7±0.5 μm. Cette valeur, très proche de la valeur 3.7± 1.2 μm déduite de la largeur de la distribution spectraledes plasmons, indique que l’élargissement spectral des plasmons propagatifs est homogène.Nous avons aussi étudié la diffusion des plasmons propagatifs excités par la pointe du STM par desnanoparticules d’or déposées sur un film d’épaisseur 50 nm. Nous observons une diffusion élastique et unediffusion radiative. Des franges d’interférences sont observées dans la région d’émission lumineuseinterdite du plan de Fourier, dont la période est inversement proportionnelle à la distancepointe-nanoparticule d’or avec un facteur de proportionnalité égal à la longueur d’onde moyenne desplasmons. Il y a donc interférence entre la radiation des plasmons localisés et la radiation provenant de ladiffusion des plasmons propagatifs sur les nanoparticules d’or. Ceci indique que les plasmons localisés etpropagatifs excités électriquement par la pointe du STM sont différentes composantes du plasmon uniqueproduit par effet tunnel inélastique avec la pointe du STM. Ces résultats originaux sur les plasmons créés sur film d’or par un effet tunnel inélastique localisé à l’échelle atomique (i) élargissent la compréhension du processus et (ii) offrent des perspectives intéressantes pour une association de la nanoélectronique et de la nanophotonique. / For the first time, using a equipment combining a scanning tunneling microscope (STM) and an invertedoptical microscope, we excite and directly image STM-excited broadband propagating surface plasmons ona thin gold film. The STM-excited propagating surface plasmons have been imaged both in real space andFourier space by leakage radiation microscopy. Broadband localized surface plasmons due to the tip-goldfilm coupled plasmon resonance have also been detected. Quantitatively, we compare the intensities ofSTM-excited propagating and localized surface plasmons obtained with different STM tips. We find that the intensity of each plasmon mode can be selectively varied by changing the STM tip shape or material composition. A silver tip produces a high intensity of localized surface plasmons whereas a sharp (radius < 100 nm) tungsten tip produces mainly propagating surface plasmons. We have investigated the coherence of STM-excited propagating surface plasmons by performingexperiments on a 200 nm thick (opaque) gold film punctured by pairs of nanoholes. This work is analogousto Young’s double-slit experiment, and shows that STM-excited propagating surface plasmons have acoherence length of 4.7±0.5 μm. This coherent length is very close to the value 3.7±1.2 μm expected fromthe spectrum, which indicates that the spectrum broadening of STM-excited surface plasmons ishomogeneous. We have also studied the in-plane and radiative scattering of STM-excited propagating surface plasmons bygold nanoparticles deposited on a 50 nm thick gold film. In the Fourier space images, interference fringesare observed in the forbidden light region. This interference occurs between STM-excited localized surfaceplasmons (radiating at large angles from the tip position) and the radiative scattering by the goldnanoparticle of STM-excited propagating surface plasmons. This indicates that STM-excited localized andpropagating surface plasmons are different components of the same single plasmon produced by inelasticelectron tunneling with the STM tip. These results not only broaden the understanding about the excitation process of STM excited surface plasmons but also offer interesting perspectives for the connection between nanoelectronics andnanophotonics.

<p>This thesis contains three papers investigating problems of interest for noise control in ducts.</p><p>The first part of this thesis treats the sound propagation in rectangular ducts with flexible walls. Various experimental techniques are performed to measure the internal sound propagation and radiation to the surrounding. An analytical model is derived to calculate the coupled propagation wavenumber and radiated sound power. The two-port formalism is used.</p><p>The second part starts with the sound propagation in open ended circular straight pipe with airflow (a tailpipe). Various aspects such as: acoustic damping, reflection and transmission at the open termination are investigated. Sound absorption due to vorticity shed at the opening is also treated. The geometry of the opening is then modified (oblique cuts, diffusers) and comparisons with the reference straight pipe is made for the sound transmission and flow induced noise generation. The effect of an upstream bend close to the opening is also investigated.</p><p>In the third part the acoustic impedance of perforated plates are investigated. In particular the application to small perforation ratios ( ≈ 1% ) and holes or slits with apertures of sub-millimetre size, so called micro-perforated plates, are of interest. Linear and non-linear regimes are investigated. A model is derived to calculate the linear acoustic impedance of perforated elements.</p>

L'hadronthérapie joue un rôle de plus en plus important au sein des techniques de radiothérapie grâce aux propriétés balistiques des ions et, dans le cas de ceux plus lourds que les protons, à une augmentation de l'efficacité biologique dans la région tumorale. Ces caractéristiques permettent une meilleure conformation de la dose délivrée au volume tumoral et elles permettent en particulier de traiter des tumeurs radio-résistantes. Elles conduisent cependant à une grande sensibilité du parcours des ions aux incertitudes du traitement. C'est dans ce contexte qu'a été proposée la détection de radiations secondaires émises lors des interactions nucléaires induites par les ions incidents dans le patient. La tomographie par émission de positons et la détection des rayons gamma prompts ont notamment fait l'objet d'une recherche intense ces dernières années. Le réseau de formation européen ENTERVISION, soutenu par la communauté ENLIGHT, a été crée fin 2009 pour développer ce type d'imagerie et, plus généralement, traiter les incertitudes de traitement en hadronthérapie. Le travail présenté dans ce manuscrit et intitulé ≪ Modélisation et simulation des processus physiques pour l'imagerie en ligne de l'hadronthérapie ≫ est l'un des nombreux travaux issus de ce projet. Bien que le sujet soit particulièrement large, le fil conducteur de ce travail a été une étude systématique visant in fine une implémentation d'un dispositif d'imagerie ≪ gamma prompts ≫ utilisable à la fois en faisceau de protons et d'ions carbone / Hadrontherapy is taking an increasingly important role in radiotherapy thanks to the ballistic properties of ions and, for those heavier than protons, an enhancement in the relative biological effectiveness in the tumour region. These features allow for a higher tumour conformality possible and gives the opportunity to tackle the problem of radioresistant tumours. However, they may lead to a great sensitivity of ion range to treatment uncertainties, namely to morphological changes along their path. In view of this, the detection of secondary radiations emitted after nuclear interactions between the incoming ions and the patient have been long proposed as ion range probes and, in this regard, positron emitters and prompt gammas have been the matter of intensive research. The European training network ENTERVISION, supported by the ENLIGHT community, was created in the end of 2009 in order to develop such imaging techniques and more generally to address treatment uncertainties during hadrontherapy. The present work is one of the many resulting from this project, under the subject “Modelling and simulation of physics processes for in-beam imaging in hadrontherapy”. Despite the extensive range of the topic, the purpose was always to make a systematic study towards the clinical implementation of a prompt-gamma imaging device to be used for both proton and carbon ion treatments

No description available.

This thesis contains three papers investigating problems of interest for noise control in ducts. The first part of this thesis treats the sound propagation in rectangular ducts with flexible walls. Various experimental techniques are performed to measure the internal sound propagation and radiation to the surrounding. An analytical model is derived to calculate the coupled propagation wavenumber and radiated sound power. The two-port formalism is used. The second part starts with the sound propagation in open ended circular straight pipe with airflow (a tailpipe). Various aspects such as: acoustic damping, reflection and transmission at the open termination are investigated. Sound absorption due to vorticity shed at the opening is also treated. The geometry of the opening is then modified (oblique cuts, diffusers) and comparisons with the reference straight pipe is made for the sound transmission and flow induced noise generation. The effect of an upstream bend close to the opening is also investigated. In the third part the acoustic impedance of perforated plates are investigated. In particular the application to small perforation ratios ( ≈ 1% ) and holes or slits with apertures of sub-millimetre size, so called micro-perforated plates, are of interest. Linear and non-linear regimes are investigated. A model is derived to calculate the linear acoustic impedance of perforated elements. / QC 20101111

Designing mechanical products in a competitive environment can present unique challenges, and designers constantly search for innovative ways to increase efficiency. One way to save space and reduce cost is to use ortho-planar compliant mechanisms which can be made from sheets of material, or lamina emergent mechanisms (LEMs). This thesis presents principles which can be used for designing LEMs. Pop-up paper mechanisms use topologies similar to LEMs, so it is advantageous to study their kinematics. This thesis outlines the use of planar and spherical kinematics to model commonly used pop-up paper mechanisms. A survey of common joint types is given, as well as an overview of common monolithic and layered mechanisms. In addition, it is shown that more complex mechanisms may be created by combining simple mechanisms in various ways. The principles presented are applied to the creation of new pop-up joints and mechanisms, which also may be used for lamina emergent mechanisms. Models of the paper mechanisms presented in Chapter 2 of the thesis are found in the appendix, and the reader is encouraged to print, cut out and assemble them. One challenge associated with spherical and spatial LEM design is creating joints with the desired motion characteristics, especially where complex spatial mechanism topologies are required. Hence, in addition to a study of paper mechanisms, some important considerations for designing joints for LEMs are presented. A technique commonly used in robotics, using serial chains of revolute and prismatic joints to approximate the motion of complex joints, is presented for use in LEMs. Important considerations such as linkage configuration and mechanism prototyping are also discussed. Another challenge in designing LEMs is creating multi-stable mechanisms with the ability to have coplanar links. A method is presented for offsetting the joint axes of a spatial compliant mechanism to introduce multi-stability. A new bistable spatial compliant linkage that uses that technique is introduced. In the interest of facilitating LEM design, the final chapter of this thesis presents a preliminary design method. While similar to traditional methods, this method includes considerations for translating the mechanism topology into a suitable configuration for use with planar layers of material.

Le syndrome néphrotique idiopathique (SNI) se caractérise par un remodelage du cytosquelette des podocytes et par une réorganisation des complexes protéiques podocytaires dont le diaphragme de fente. Récemment, une protéine fondamentale dans le remodelage du cytosquelette a été identifiée au niveau des pédicelles : IQGAP1. Nous sommes partis de l’hypothèse selon laquelle IQGAP1 par ses propriétés et ses caractéristiques biologiques connues dans différents modèles cellulaires (protéine d’échafaudage, remodelage du cytosquelette, migration cellulaire) pourrait être fondamentale dans les modifications ultrastructurales observées au cours du SNI. Au cours de ce travail de thèse, nous avons analysé les caractéristiques de la protéine IQGAP1 dans les podocytes humains, son implication dans les fonctions podocytaires et dans la physiopathologie du SNI. Nous avons dans un premier temps caractérisé les propriétés de la protéine IQGAP1 au sein des podocytes et déterminé sa localisation cellulaire à l’interface entre le cytosquelette et les complexes protéiques apical et diaphragmatique. Nous avons démontré le rôle d’IQGAP1 dans la migration podocytaire et dans la perméabilité de la monocouche épithéliale. Ces phénomènes au cours du SNI étant modifiés, nous avons dans un second temps étudié l’implication d’IQGAP1 dans la physiopathologie du SNI à l’aide de différents modèles expérimentaux (aminonucléoside de puromycine, plasmas de patients présentant un SNI, podocytes mutés pour la PLCε1). Nous avons ainsi démontré la translocation nucléaire de la protéine IQGAP1, dépendante de la voie ERK et de la PLCε1 et son implication dans la survie cellulaire par son interaction avec la chromatine. Au cours du SNI expérimental, nous avons observé une modification des propriétés d’IQGAP1 : localisation, interactions, phosphorylation.Cette approche a permis de démontrer l’implication de la protéine IQGAP1 dans le SNI. Compte tenu de son rôle dans le remodelage du cytosquelette, IQGAP1 pourrait également être un facteur dans la genèse de différentes glomérulopathies. / Idiopathic nephrotic syndrome (INS) is characterized by the pedicel cytoskeleton remodelling and the disruption of the slit diaphragm complex. Recently, a pivotal protein involved in cytoskeleton remodelling has been identified in podocytes: IQGAP1.We hypothesized that IQGAP1 may be crucial in ultrastructure changes observed in INS through its biological properties and characteristics reported in different cell types (scaffold protein, cytoskeleton dynamism, cell migration). Thus, we analysed IQGAP1 characteristics in human podocytes, its involvement in podocyte functions and in the INS pathophysiology. We have characterized IQGAP1 podocyte characteristics and clarified its cell localisation between the cytoskeleton and the apical or diaphragmatic protein complexes Our work demonstrated the role of IQGAP1 in podocyte motility and in the permeability of epithelial monolayer. With respect to the modification of these phenomenons during INS, we have studied IQGAP1 involvement in INS pathophysiology with different experimental models (puromycine aminonucleoside, plasmas from patients suffering from INS, PLCε1 mutated podocytes). We have demonstrated IQGAP1 nuclear translocation, dependant to ERK signaling pathway and to PLCε1 and its involvement in cell survival through its interaction with the chromatin. In the experimental INS, we have observed a modification of IQGAP1 properties: localization, interactions, phosphorylation. This approach allowed us to show IQGAP1 involvement in INS. Through its role in cytoskeleton remodelling, IQGAP1 may be a factor in the development of different glomerulopathies.