Snap-through is a striking instability in which an elastic object rapidly jumps from one state to another. It is seen in the leaves of the Venus flytrap plant and umbrellas flipping on a windy day among many other examples. Similar structures that snap-through are used to generate fast motions in soft robotics, switches in micro-scale electronics and artificial heart valves. Despite the ubiquity of snap-through in nature and engineering, its dynamics is usually only understood qualitatively. In this thesis we develop analytical understanding of this dynamics, focussing on how the mathematical structure underlying the snap-through transition controls the timescale of instability. We begin by considering the dynamics of 'pull-in' instabilities in microelectromechanical systems (MEMS) - a type of snap-through caused by electrostatic forces in which the motions are dominated by fluid damping. Using a lumped-parameter model, we show that the observed time delay near the pull-in transition is a type of critical slowing down - a so-called 'bottleneck' due to the 'ghost' of a saddle-node bifurcation. We obtain a scaling law describing this slowing down, and, in the process, unify a large range of experiments and simulations that exhibit delay phenomena during pull-in. We also investigate the pull-in dynamics of MEMS microbeams, extending the lumped-parameter approach to incorporate the details of the beam geometry. This provides a model system in which to understand snap-through of a continuous elastic structure due to external loading. We develop a perturbation method that systematically exploits the proximity to pull-in to reduce the governing equations to a simpler evolution equation, with a structure that highlights the saddle-node bifurcation. This allows us to analyse the bottleneck dynamics in detail, which we compare with previous experimental and numerical data. The remainder of the thesis is concerned with the dynamics of snap-through in macroscopic systems. In particular, we explore the extent to which dissipation is required to explain anomalously slow snap-through. Considering an elastic arch as an archetype of a snapping system, we use the perturbation method developed earlier to show that two bottleneck regimes are possible, depending delicately on the relative importance of external damping. In particular, we show that critical slowing down occurs even in the absence of damping, leading to a new scaling law for the snap-through time that is confirmed by elastica simulations and experiments. In many real systems material viscoelasticity is present to some degree. Finally, we examine how this influences the snap-through dynamics of a simple truss-like structure. We present a regime diagram that characterises when the timescale of snap-through is controlled by viscous, elastic or viscoelastic effects.

One major step needed for fusion to become a reliable energy source is the development of materials for the extreme conditions (high temperature, radioactivity and erosion) caused by hot plasmas. The main goal of the present study is to use and optimise ion beam methods (lateral resolution and sensitivity) to characterise the distribution of hydrogen isotopes that act as fuel. Materials from the test reactors JET (Joint European Torus), TEXTOR (Tokamak Experiment for Technology Oriented Research) and Tore Supra have been investigated. Deuterium, beryllium and carbon were measured by elastic recoil detection analysis (ERDA) and nuclear reaction analysis (NRA). To ensure high 3D spatial resolution a nuclear microbeam (spot size <10 µm) was used with 3He and 28Si beams. The release of hydrogen caused by the primary ion beam was monitored and accounted for. Large variations in surface (top 10 µm) deuterium concentrations in carbon fibre composites (CFC) from Tore Supra and TEXTOR was found, pointing out the importance of small pits and local fibre structure in understanding fuel retention. At deeper depths into the CFC limiter tiles from Tore Supra, deuterium rich bands were observed confirming the correlation between the internal material structure and fuel storage in the bulk. Sample cross sections from thick deposits on the JET divertor showed elemental distributions that were dominantly laminar although more complex structures also were observed. Depth profiles of this kind elucidate the plasma-wall interaction and material erosion/deposition processes in the reactor vessel. The information gained in this thesis will improve the knowledge of first wall material for the next generation fusion reactors, concerning the fuel retention and the lifetime of the plasma facing materials which is important for safety as well as economical reasons.

Two innovative radiotherapy (RT) approaches are under development at the ID17 Biomedical Beamline of the European Synchrotron Radiation Facility (ESRF): microbeam radiation therapy (MRT) and minibeam radiation therapy (MBRT). The two main distinct characteristics with respect to conventional RT are the use of submillimetric field sizes and spatial fractionation of the dose. This PhD work deals with different features related to small-field dosimetry involved in these techniques. Monte Carlo (MC) calculations and several experimental methods are used with this aim in mind. The core of this PhD Thesis consisted of the development and benchmarking of an MC-based computation engine for a treatment planning system devoted to MRT within the framework of the preparation of forthcoming MRT clinical trials. Additional achievements were the definition of safe MRT irradiation protocols, the assessment of scatter factors in MRT, the further improvement of the MRT therapeutic index by injecting a contrast agent into the tumour and the definition of a dosimetry protocol for preclinical trials in MBRT.

Neste trabalho, o processo de estruturação por microfeixe de íons foi utilizado para a produção de membranas microporosas em folhas comerciais de PET. O processo de estruturação por microfeixe de íons consiste basicamente na interação direta entre um feixe de íons de dimensões micrométricas com o material em questão. As zonas modificadas pelo feixe são removidas do restante do material através de um processo químico. Nesse contexto, durante o desenvolvimento deste trabalho, sistemáticas experimentais para o processo de estruturação foram desenvolvidas. Com o intuito de operacionalizar a linha de microfeixe presente no Laboratório de Implantação Iônica da UFRGS, foi necessário realizar um estudo aprofundado sobre o funcionamento de todo o sistema, verificando problemas e explorando a potencialidade de técnicas não convencionais de análise de materiais. O estudo sobre a sistemática de estruturação ocorreu através da investigação de parâmetros clássicos, como fluência utilizada durante a irradiação e tempo de ataque químico. Para atingir tais objetivos, amostras de poli (tereftalato de etileno) (Mylar) de 12 μm foram irradiadas com microfeixe de íons (H+ e He++) com energias de 3 e 2,2 MeV e fluências que variaram entre 1 x 1011 e 6 x 1015 íons/cm2. Posteriormente à irradiação, as amostras foram submetidas a um ataque químico com solução alcalina de hidróxido de sódio 6 M durante tempos que variaram de 0,5 à 60 minutos. A temperatura do ataque em todos os casos se manteve fixa em 60°C. A caracterização das amostras foi realizada através de microscopia eletrônica de varredura (MEV) e por microscopia de transmissão iônica (STIM). As amostras também foram caracterizadas através de medidas elétricas utilizando um circuito de corrente alternada. O processo de enxertia (grafting) foi testado nas membranas estruturadas, utilizando um hidrogel de PNIPAAm com concentrações de 0,340, 0,450 e 0,700 g/L. Tais resultados também foram analisados através de MEV. O estudo sobre a linha de microfeixe permitiu verificar a existência de problemas relacionados ao registro da carga elétrica durante as irradiações. Além disso, para o ajuste do foco do feixe de íons, foram feitas curvas de calibração de corrente para as lentes magnéticas considerando diferentes energias de feixe. O processo de estruturação através da técnica de microfeixe de íons se mostrou eficaz para a produção de estruturas regulares e definidas em folhas de PET. A fluência ótima de prótons a ser utilizada nos processos de estruturação foi estimada em 6 x 1014 íons/cm2. Para esta fluência, tempos de ataque químico inferiores a 1 minuto já são suficientes para corroer toda a parte irradiada. Entretanto, tempos um pouco mais longos (e.g. 2 minutos) tornam o processo mais reprodutível. Com relação à geometria das estruturas fabricadas, observou-se irregularidades em estruturas que, em princípio, deveriam ser simétricas. Esse problema foi atribuído à assimetria do feixe, proveniente de ajustes dos parâmetros de colimação do feixe. Finalmente, o estudo do processo de enxertia mostrou que o hidrogel adere nas paredes das estruturas, porém não as preenche. Para concentrações elevadas (e.g. 0,7 g/L) o processo não é tão eficiente, sendo que não é verificada a redução da área das microestruturas pela inserção do hidrogel. As medidas elétricas mostraram a existência de regimes distintos e dependentes da frequência da corrente alternada. Os polímeros apresentaram basicamente comportamentos resistivo e capacitivo. / In this work, the process of irradiation of PET foils with ion beams in the micrometer size range was used for the production of microporous membranes. Basically, this process consists on the direct interaction between the ion beam and the material under study. The regions modified by the beam are removed from the material through a chemical process. In this context, experimental procedures for the production process of the membranes were developed during the course of this work. In order to make the microbeam station of the Ion Implantation Laboratory of the Federal University of Rio Grande do Sul (UFRGS), it was necessary to perform a thorough study of the operational parameters of the system, thus allowing a proper identification of problems and providing grounds for pushing the technique to the frontier of materials science. To achieve such objectives, foils of polyethylene terephtalate (Mylar®) 12 μm thick were irradiated with H+ and He++ ions with 3 e 2,2 MeV respectively. Fluencies varied from 1 x 1011 and 6 x 1015 ions/cm2. After the irradiation, the foils were submitted to an etching procedure using alkaline solution of sodium hydroxide at 6 M during periods of time varying from 0,5 to 60 minutes. In all cases, the temperature of the etching was fixed at 60°C. The characterization of the samples was performed through scanning electron microscopy (SEM) and scanning transmission ion microscopy (STIM). The samples also were characterized by electric measurements using an AC current circuit. The process of grafting was tested on the structured membranes using a PNIPAAm hydrogel with concentrations of 0,340, 0,450 and 0,700 g/L. The results of this study were also analyzed through MEV. With the present study, it was possible to pinpoint problems related to the integration and recording of the charge during the irradiations. Besides that, calibration curves were obtained relating the electric currents needed on the magnetic lenses for an optimal ion beam focus and the beam energy. The irradiation process with ion beam proved itself efficient for the production of regular patterns on PET foils. The optimum dose of prótons to be used on the patterning processes was estimated in 6 x 1014 ions/cm2. For this dose, etching times smaller than 1 minute were enough to remove all the irradiated area. However, times slightly longer (e.g. 2 minutes) make the process more reproducible. Regarding the geometry of the patterns generated by the ion irradiation, asymmetries were observed on structures that were supposed to be symmetric. This problem was attributed to the asymmetry of the beam spot on the target due to the settings of the objective slits that collimates the beam. The study of the grafting process showed that the hydrogel adheres to the structures walls, but does not fill it. For high concentrations (e.g. 0,7 g/L), the process is not efficient, since no reduction of the area of the microstructures by the insertion of the hydrogel was observed. The electric measurements showed the existence of distinct regimes as a function of the frequency of the alternate current. Basically, the polymer foils present resistive and capacitive behaviors.

Neste trabalho, o processo de estruturação por microfeixe de íons foi utilizado para a produção de membranas microporosas em folhas comerciais de PET. O processo de estruturação por microfeixe de íons consiste basicamente na interação direta entre um feixe de íons de dimensões micrométricas com o material em questão. As zonas modificadas pelo feixe são removidas do restante do material através de um processo químico. Nesse contexto, durante o desenvolvimento deste trabalho, sistemáticas experimentais para o processo de estruturação foram desenvolvidas. Com o intuito de operacionalizar a linha de microfeixe presente no Laboratório de Implantação Iônica da UFRGS, foi necessário realizar um estudo aprofundado sobre o funcionamento de todo o sistema, verificando problemas e explorando a potencialidade de técnicas não convencionais de análise de materiais. O estudo sobre a sistemática de estruturação ocorreu através da investigação de parâmetros clássicos, como fluência utilizada durante a irradiação e tempo de ataque químico. Para atingir tais objetivos, amostras de poli (tereftalato de etileno) (Mylar) de 12 μm foram irradiadas com microfeixe de íons (H+ e He++) com energias de 3 e 2,2 MeV e fluências que variaram entre 1 x 1011 e 6 x 1015 íons/cm2. Posteriormente à irradiação, as amostras foram submetidas a um ataque químico com solução alcalina de hidróxido de sódio 6 M durante tempos que variaram de 0,5 à 60 minutos. A temperatura do ataque em todos os casos se manteve fixa em 60°C. A caracterização das amostras foi realizada através de microscopia eletrônica de varredura (MEV) e por microscopia de transmissão iônica (STIM). As amostras também foram caracterizadas através de medidas elétricas utilizando um circuito de corrente alternada. O processo de enxertia (grafting) foi testado nas membranas estruturadas, utilizando um hidrogel de PNIPAAm com concentrações de 0,340, 0,450 e 0,700 g/L. Tais resultados também foram analisados através de MEV. O estudo sobre a linha de microfeixe permitiu verificar a existência de problemas relacionados ao registro da carga elétrica durante as irradiações. Além disso, para o ajuste do foco do feixe de íons, foram feitas curvas de calibração de corrente para as lentes magnéticas considerando diferentes energias de feixe. O processo de estruturação através da técnica de microfeixe de íons se mostrou eficaz para a produção de estruturas regulares e definidas em folhas de PET. A fluência ótima de prótons a ser utilizada nos processos de estruturação foi estimada em 6 x 1014 íons/cm2. Para esta fluência, tempos de ataque químico inferiores a 1 minuto já são suficientes para corroer toda a parte irradiada. Entretanto, tempos um pouco mais longos (e.g. 2 minutos) tornam o processo mais reprodutível. Com relação à geometria das estruturas fabricadas, observou-se irregularidades em estruturas que, em princípio, deveriam ser simétricas. Esse problema foi atribuído à assimetria do feixe, proveniente de ajustes dos parâmetros de colimação do feixe. Finalmente, o estudo do processo de enxertia mostrou que o hidrogel adere nas paredes das estruturas, porém não as preenche. Para concentrações elevadas (e.g. 0,7 g/L) o processo não é tão eficiente, sendo que não é verificada a redução da área das microestruturas pela inserção do hidrogel. As medidas elétricas mostraram a existência de regimes distintos e dependentes da frequência da corrente alternada. Os polímeros apresentaram basicamente comportamentos resistivo e capacitivo. / In this work, the process of irradiation of PET foils with ion beams in the micrometer size range was used for the production of microporous membranes. Basically, this process consists on the direct interaction between the ion beam and the material under study. The regions modified by the beam are removed from the material through a chemical process. In this context, experimental procedures for the production process of the membranes were developed during the course of this work. In order to make the microbeam station of the Ion Implantation Laboratory of the Federal University of Rio Grande do Sul (UFRGS), it was necessary to perform a thorough study of the operational parameters of the system, thus allowing a proper identification of problems and providing grounds for pushing the technique to the frontier of materials science. To achieve such objectives, foils of polyethylene terephtalate (Mylar®) 12 μm thick were irradiated with H+ and He++ ions with 3 e 2,2 MeV respectively. Fluencies varied from 1 x 1011 and 6 x 1015 ions/cm2. After the irradiation, the foils were submitted to an etching procedure using alkaline solution of sodium hydroxide at 6 M during periods of time varying from 0,5 to 60 minutes. In all cases, the temperature of the etching was fixed at 60°C. The characterization of the samples was performed through scanning electron microscopy (SEM) and scanning transmission ion microscopy (STIM). The samples also were characterized by electric measurements using an AC current circuit. The process of grafting was tested on the structured membranes using a PNIPAAm hydrogel with concentrations of 0,340, 0,450 and 0,700 g/L. The results of this study were also analyzed through MEV. With the present study, it was possible to pinpoint problems related to the integration and recording of the charge during the irradiations. Besides that, calibration curves were obtained relating the electric currents needed on the magnetic lenses for an optimal ion beam focus and the beam energy. The irradiation process with ion beam proved itself efficient for the production of regular patterns on PET foils. The optimum dose of prótons to be used on the patterning processes was estimated in 6 x 1014 ions/cm2. For this dose, etching times smaller than 1 minute were enough to remove all the irradiated area. However, times slightly longer (e.g. 2 minutes) make the process more reproducible. Regarding the geometry of the patterns generated by the ion irradiation, asymmetries were observed on structures that were supposed to be symmetric. This problem was attributed to the asymmetry of the beam spot on the target due to the settings of the objective slits that collimates the beam. The study of the grafting process showed that the hydrogel adheres to the structures walls, but does not fill it. For high concentrations (e.g. 0,7 g/L), the process is not efficient, since no reduction of the area of the microstructures by the insertion of the hydrogel was observed. The electric measurements showed the existence of distinct regimes as a function of the frequency of the alternate current. Basically, the polymer foils present resistive and capacitive behaviors.

Neste trabalho, o processo de estruturação por microfeixe de íons foi utilizado para a produção de membranas microporosas em folhas comerciais de PET. O processo de estruturação por microfeixe de íons consiste basicamente na interação direta entre um feixe de íons de dimensões micrométricas com o material em questão. As zonas modificadas pelo feixe são removidas do restante do material através de um processo químico. Nesse contexto, durante o desenvolvimento deste trabalho, sistemáticas experimentais para o processo de estruturação foram desenvolvidas. Com o intuito de operacionalizar a linha de microfeixe presente no Laboratório de Implantação Iônica da UFRGS, foi necessário realizar um estudo aprofundado sobre o funcionamento de todo o sistema, verificando problemas e explorando a potencialidade de técnicas não convencionais de análise de materiais. O estudo sobre a sistemática de estruturação ocorreu através da investigação de parâmetros clássicos, como fluência utilizada durante a irradiação e tempo de ataque químico. Para atingir tais objetivos, amostras de poli (tereftalato de etileno) (Mylar) de 12 μm foram irradiadas com microfeixe de íons (H+ e He++) com energias de 3 e 2,2 MeV e fluências que variaram entre 1 x 1011 e 6 x 1015 íons/cm2. Posteriormente à irradiação, as amostras foram submetidas a um ataque químico com solução alcalina de hidróxido de sódio 6 M durante tempos que variaram de 0,5 à 60 minutos. A temperatura do ataque em todos os casos se manteve fixa em 60°C. A caracterização das amostras foi realizada através de microscopia eletrônica de varredura (MEV) e por microscopia de transmissão iônica (STIM). As amostras também foram caracterizadas através de medidas elétricas utilizando um circuito de corrente alternada. O processo de enxertia (grafting) foi testado nas membranas estruturadas, utilizando um hidrogel de PNIPAAm com concentrações de 0,340, 0,450 e 0,700 g/L. Tais resultados também foram analisados através de MEV. O estudo sobre a linha de microfeixe permitiu verificar a existência de problemas relacionados ao registro da carga elétrica durante as irradiações. Além disso, para o ajuste do foco do feixe de íons, foram feitas curvas de calibração de corrente para as lentes magnéticas considerando diferentes energias de feixe. O processo de estruturação através da técnica de microfeixe de íons se mostrou eficaz para a produção de estruturas regulares e definidas em folhas de PET. A fluência ótima de prótons a ser utilizada nos processos de estruturação foi estimada em 6 x 1014 íons/cm2. Para esta fluência, tempos de ataque químico inferiores a 1 minuto já são suficientes para corroer toda a parte irradiada. Entretanto, tempos um pouco mais longos (e.g. 2 minutos) tornam o processo mais reprodutível. Com relação à geometria das estruturas fabricadas, observou-se irregularidades em estruturas que, em princípio, deveriam ser simétricas. Esse problema foi atribuído à assimetria do feixe, proveniente de ajustes dos parâmetros de colimação do feixe. Finalmente, o estudo do processo de enxertia mostrou que o hidrogel adere nas paredes das estruturas, porém não as preenche. Para concentrações elevadas (e.g. 0,7 g/L) o processo não é tão eficiente, sendo que não é verificada a redução da área das microestruturas pela inserção do hidrogel. As medidas elétricas mostraram a existência de regimes distintos e dependentes da frequência da corrente alternada. Os polímeros apresentaram basicamente comportamentos resistivo e capacitivo. / In this work, the process of irradiation of PET foils with ion beams in the micrometer size range was used for the production of microporous membranes. Basically, this process consists on the direct interaction between the ion beam and the material under study. The regions modified by the beam are removed from the material through a chemical process. In this context, experimental procedures for the production process of the membranes were developed during the course of this work. In order to make the microbeam station of the Ion Implantation Laboratory of the Federal University of Rio Grande do Sul (UFRGS), it was necessary to perform a thorough study of the operational parameters of the system, thus allowing a proper identification of problems and providing grounds for pushing the technique to the frontier of materials science. To achieve such objectives, foils of polyethylene terephtalate (Mylar®) 12 μm thick were irradiated with H+ and He++ ions with 3 e 2,2 MeV respectively. Fluencies varied from 1 x 1011 and 6 x 1015 ions/cm2. After the irradiation, the foils were submitted to an etching procedure using alkaline solution of sodium hydroxide at 6 M during periods of time varying from 0,5 to 60 minutes. In all cases, the temperature of the etching was fixed at 60°C. The characterization of the samples was performed through scanning electron microscopy (SEM) and scanning transmission ion microscopy (STIM). The samples also were characterized by electric measurements using an AC current circuit. The process of grafting was tested on the structured membranes using a PNIPAAm hydrogel with concentrations of 0,340, 0,450 and 0,700 g/L. The results of this study were also analyzed through MEV. With the present study, it was possible to pinpoint problems related to the integration and recording of the charge during the irradiations. Besides that, calibration curves were obtained relating the electric currents needed on the magnetic lenses for an optimal ion beam focus and the beam energy. The irradiation process with ion beam proved itself efficient for the production of regular patterns on PET foils. The optimum dose of prótons to be used on the patterning processes was estimated in 6 x 1014 ions/cm2. For this dose, etching times smaller than 1 minute were enough to remove all the irradiated area. However, times slightly longer (e.g. 2 minutes) make the process more reproducible. Regarding the geometry of the patterns generated by the ion irradiation, asymmetries were observed on structures that were supposed to be symmetric. This problem was attributed to the asymmetry of the beam spot on the target due to the settings of the objective slits that collimates the beam. The study of the grafting process showed that the hydrogel adheres to the structures walls, but does not fill it. For high concentrations (e.g. 0,7 g/L), the process is not efficient, since no reduction of the area of the microstructures by the insertion of the hydrogel was observed. The electric measurements showed the existence of distinct regimes as a function of the frequency of the alternate current. Basically, the polymer foils present resistive and capacitive behaviors.

L’interaction des particules chargées avec la matière conduit à un dépôt d’énergie très localisé dans des traces de dimensions sub-micrométriques. Cette propriété unique rend ce type de rayonnement ionisant particulièrement intéressant pour disséquer les mécanismes moléculaires radio-induits suite à l’échelle de la cellule. L’utilisation de microfaisceaux de particules chargées offre en outre la capacité d’irradier sélectivement à l’échelle du micromètre avec une dose contrôlée jusqu’à la particule unique. Mon travail a porté sur des irradiations réalisées avec le microfaisceau de particules chargées de la plateforme AIFIRA (Applications Interdisciplinaires des Faisceaux d’Ions en Région Aquitaine) du CENBG. Ce microfaisceau délivre des protons et particules alpha et est dédié aux irradiations ciblées in vitro (cellules humains) et in vivo (C. elegans).En complément de l’intérêt qu’elles présentent pour des études expérimentales, les dépôts d’énergie et les interactions des particules chargées avec la matière peuvent être modélisés précisément tout au long de leur trajectoire en utilisant des codes de structures de traces basés sur des méthodes Monte Carlo. Ces outils de simulation permettent une caractérisation précise de la micro-dosimétrie des irradiations allant de la description détaillée des interactions physiques à l’échelle nanométrique jusqu’à la prédiction du nombre de dommages à l’ADN et leurs distributions dans l’espace.Au cours de ma thèse, j’ai développée des modèles micro-dosimétriques basés sur l’outil de modélisation Geant4-DNA dans deux cas. Le premier concerne la simulation de la distribution d’énergie déposée dans un noyau cellulaire et le calcul du nombre des différents types de dommages ADN (simple et double brin) aux échelles nanométrique et micrométrique, pour différents types et nombres de particules délivrées. Ces résultats sont confrontés à la mesure expérimentale de la cinétique de protéines de réparation de l’ADN marquées par GFP (Green Fluorescent Protein) dans des cellules humaines. Le second concerne la dosimétrie de l’irradiation d’un organisme multicellulaire dans le cadre d’études de l’instabilité génétique dans un organisme vivant au cours du développement (C. elegans). J’ai simulé la distribution de l’énergie déposée dans différents compartiments d’un modèle réaliste en 3D d’un embryon de C. elegans suite à des irradiations par protons. Enfin, et en parallèle de ces deux études, j’ai développé un protocole pour caractériser le microfaisceau d'AIFIRA à l’aide de détecteurs de traces fluorescent (FNTD) pour des irradiations par protons et par particules alpha. Ce type de détecteur permet en effet de visualiser les trajectoires des particules incidentes avec une résolution de l’ordre de 200 nm et d’examiner la qualité des irradiations cellulaires réalisées par le microfaisceau. / The interaction of charged particles with matter leads to a very localized energy deposits in sub-micrometric tracks. This unique property makes this type of ionizing radiation particularly interesting for deciphering the radiation-induced molecular mechanisms at the cell scale. Charged particle microbeams (CPMs) provide the ability to target a given cell compartment at the micrometer scale with a controlled dose down to single particle. My work focused on irradiations carried out with the CPM at the AIFIRA facility in the CENBG (Applications Interdisciplinaires des Faisceaux d’Ions en Région Aquitaine). This microbeam delivers protons and alpha particles and is dedicated to targeted irradiation in vitro (human cells) and in vivo (C. elegans).In addition to their interest for experimental studies, the energy deposits and the interactions of charged particles with matter can be modeled precisely along their trajectory using track structure codes based on Monte Carlo methods. These simulation tools allow a precise characterization of the micro-dosimetry of the irradations from the detailed description of the physical interactions at the nanoscale to the prediction of the number of DNA damage, their complexity and their distribution in space.During my thesis, I developed micro-dosimetric models based on the Geant4-DNA modeling toolkit in two cases. The first concerns the simulation of the energy distribution deposited in a cell nucleus and the calculation of the number of different types of DNA damage (single and double strand breaks) at the nanometric and micrometric scales, for different types and numbers of delivered particles. These simulations are compared with experimental measurements of the kinetics of GFP-labeled (Green Fluorescent Protein) DNA repair proteins in human cells. The second is the dosimetry of irradiation of a multicellular organism to study the genetic instability in a living organism during development (C. elegans). I simulated the distribution of the energy deposited in different compartments of a realistic 3D model of a C. elegans embryo following proton irradiations. Finally, and in parallel with these two studies, I developed a protocol to characterize the AIFIRA microbeam using fluorescent nuclear track detector (FNTD) for proton and alpha particle irradiations. This type of detector makes it possible to visualize in 3D the incident particle tracks with a resolution of about 200 nm and to examine the quality of the cellular irradiations carried out by the CPM.

No description available.

<p>Microbeam radiation therapy (MRT) is an experimental radiotherapy concept that has been primarily developed for the treatment of malignant brain tumours. MRT uses high flux synchrotron x-rays delivered as an array of parallel microbeams in high doses of irradiation in fractions of seconds. The aims of this study were to 1) investigate the induction of bystander effects after normal and tumour-bearing rat brains were exposed to MRT and homogenous radiation; 2) validate a brain bystander proteome by detecting protein expression throughout immunohistochemistry: and 3) to investigate whether communication of bystander signals can be produced between animals.</p> <p>Healthy and tumour-bearing Wistar rats were exposed to 17.5, 35, 70 or 350 Gy of MRT or homogenous field of synchrotron radiation to the right brain hemisphere. To study the communication of bystander effects between animals, irradiated rats shared the same cage with non-irradiated rats over a period of 48 hours. After euthanasia of the animals, brains and bladders were dissected, and samples for immunohistochemistry and bystander clonogenic assays were set up.</p> <p>Clonogenic survival of the reporter HPVG cells showed that bystander effects occurred in both the non-irradiated hemisphere and bladder of normal and tumour-bearing rats, while the irradiated hemisphere showed the direct effects of radiation. Moreover, communication of bystander signals was confirmed in the non-irradiated rats.</p> <p>In conclusion, the results suggest that the MRT and homogenous radiation of unilateral normal and tumour-bearing rat brains produce bystander signals that affect the whole organism and that those signals also can be transmitted to non-irradiated animals.</p> / Master of Science (MSc)

The techniques of small-angle x-ray scattering (SAXS) and grazing-incidence small-angle x-ray scattering (GISAXS) have successfully been used for many years in the analysis of nanostructures in non-crystalline samples, e.g., polymers, metallic alloys, ceramics, and glasses. In many specimens, however, the nanostructure is not distributed homogeneously, but instead varies as a function of position in the sample. Conventional SAXS or GISAXS measurements on such heterogeneous samples merely yield an averaged scattering pattern of all the different structures present along the x-ray beam path. In this thesis, scanning tomography is combined with SAXS and GISAXS, revealing the individual local scattering cross section at each position on a virtual section through the sample. The technique thereby offers unique analytical possibilities in heterogeneous specimens. A brief review of the physics of x rays and x-ray scattering is given, before the methods of tomographic SAXS and GISAXS are introduced. Experimental requirements and limitations of both methods are discussed, including aspects of sampling, local rotational invariance and x-ray beam coherence. Experiments performed at the beamline BW4 at HASYLAB at DESY, Hamburg, Germany are described, illustrating the capabilities of the method. Finally, an outlook on possible future developments in tomographic small-angle x-ray scattering is given. / Die Methoden der Röntgenkleinwinkelstreuung (SAXS) und Röntgenkleinwinkelstreuung unter streifendem Einfall (GISAXS) werden seit vielen Jahren erfolgreich eingesetzt zur Analyse von Nanostrukturen in nicht-kristallinen Proben, z.B. Polymeren, metallischen Legierungen, Keramiken und Gläsern. In vielen Proben ist die Nanostruktur allerdings nicht homogen verteilt, sondern variiert als Funktion des Ortes in der Probe. Konventionelle SAXS- oder GISAXS-Messungen an solch heterogenen Proben liefern lediglich ein über alle unterschiedlichen Strukturen entlang des Röntgenstrahls gemitteltes Streubild. In dieser Arbeit wird Rastertomographie mit SAXS und GISAXS kombiniert und so der lokale Streuquerschnitt an jedem Ort auf einem virtuellen Schnitt durch die Probe gewonnen. Diese Technik bietet so einzigartige Analysemöglichkeiten von heterogenen Proben. Es wird zunächst ein kurzer Überblick über die Physik der Röntgenstrahlung und Röntgenstreuung gegeben, bevor die Methoden der SAXS- und GISAXS-Tomographie eingeführt werden. Die experimentellen Anforderungen und Grenzen beider Methoden werden besprochen, wobei Aspekte der Abtastung, der lokalen Rotationsinvarianz und der Kohärenz im Röntgenstrahl eine Rolle spielen. Experimente, die an der Messstrecke BW4 am HASYLAB bei DESY, Hamburg, durchgeführt wurden, werden beschrieben, um die Möglichkeiten der Methode zu illustrieren. Schließlich wird ein Ausblick auf mögliche zukünftige Entwicklungen der Kleinwinkelstreutomographie gegeben.