Magister Scientiae (Medical Bioscience) - MSc(MBS) / Despite the advances in therapies such as chemotherapy and radiotherapy, tumours have been shown to be resistant to the treatments. Gold nanoparticles (AuNPs) have been recognized as effective radiosensitizers of low energy (e.g. 200–500 kV) X-rays, leading to the emission of Auger electrons that cause highly localised ionizing damage to cells. Spherical AuNPs were synthesised via the reduction of the chloroaurate ions by sodium citrate. Characterisation of AuNPs involved UV-visible spectrophotometry, zeta (Z) potential, dynamic light scattering (DLS) and polydispersity index (PDI) measurements for determination of surface plasmon resonance (SPR), surface charge and stability, as well as transmission electron microscopy (TEM) for hydrodynamic core sizes, size distribution width and shape of AuNPs. Both the 5 and 10 nm AuNPs were found to be anionic with λmax absorbance of 525 nm and uniform size distribution. DLS measurement at 38.12 nm and 48.50 nm, respectively for 5 nm and 10 nm AuNPs, points to aggregation of the AuNPs. However, TEM measurements confirmed the core size of the 10 nm AuNPs. Non-malignant Chinese hamster ovary (CHO-K1), brain endothelial (BEnd5), breast (MCF-10A), isolated human lymphocytes and malignant breast (MCF-7) cell lines were treated with 50 μg/ml of AuNPs, and irradiated with either 1, 2 or 4 Gy X-rays or 1 or 2 Gy p(66)/Be neutron radiation. The γ-H2AX foci assay, cytokinesis-block micronucleus assay, MTT assay and fluorescence-activated cell sorting (FACS) was used to determine that amount of double stranded breaks (DSBs) in isolated lymphocytes, the presence and number of micronuclei (MNi) within binucleated cells (BNCs), cell viability and cell cycle progression, respectively. Preliminary experiments that established the reliability of the study regarding the induction of DNA damage after the bombardment of AuNPs by scattered low kV X-rays, were carried out on lymphocytes. Combined treatment (AuNPs and radiation) resulted in more endogenous foci in comparison to lymphocytes that were treated with AuNPs only. The CHO-K1 and MCF-7 cells showed higher MNi frequencies after the combination treatment of AuNPs and radiation compared to the number of MNi in samples exposed to AuNPs and radiation separately. The AuNPs alone influenced the cellular kinetics of all cell types. Interaction indices, which is the enhancement factor of AuNPs in combination with radiation, for AuNPs and 6 MV 2 Gy X-rays of 1.6 to 1.7 and 1.3 to 1.4 have respectively been determined for CHO-K1 and MCF-7 cells, whilst that for the other cell types used in the study were not different from Unity. As expected, the interaction indices between AuNPs and p(66)/Be neutrons was lower than the interaction indices after 2 Gy X-rays, as p(66)/Be neutrons interact only with the nuclei of the AuNP's atoms and the X-ray photons interact with the orbital electrons of the atoms of the AuNPs leading to Auger electron emission. The cell viability assay showed that 50 μg/ml of AuNPs had an inhibitory effect on cellular proliferation, in all four cell linnes whereas the lower concentrations (2.5, 5 and 10 μg/ml) had no effect. Results in this study, revealed an increase in the accumulation of CHO-K1 an MCF-7 cells in the G₂/M phase of the cell cycle after being treated with AuNPs followed by X-ray radiation, suggesting that the cells have possibly been sensitised to the damaging effects of radiation. Further studies are required to quantify internalised AuNPs and to then link the possible concentration differences of the AuNPs to differences in radiation damage effects observed for the different cell types.

La ptychographie est une technique d’imagerie par diffraction cohérente qui vise à récupérer la phase perdue, uniquement par des mesures d’intensité en champ lointain. Cette technique permet l’imagerie des champs de déformation dans des cristaux périodiques avec des résolutions sous-faisceau. Dans ce travail, la ptychographie de Bragg en 3D est utilisée pour étudier les propriétés d’une couche cristalline nanostructurée de InP/InGaAs collée sur un substrat de silicium. L’expérience a été réalisée sur la ligne ID13 de l’ESRF, avec un faisceau monochromatique concentré à 100nm. Les intensités 2D ont été acquises avec plusieurs angles d’incidence dans le voisinage du pic de Bragg InP (004), empilant un jeu de données tridimensionnelles. L’analyse numérique du problème donné a été effectuée à l’avance afin d’optimiser la stratégie d’inversion et d’étudier la possibilité d’introduire des contraintes physiques supplémentaires basées sur des approches de régularisation. L’inversion de l’ensemble des données a été effectuée en utilisant un algorithme ptychographique de reconstruction de phase. L’image 3D récupérée représente la haute qualité cristalline de l’échantillon, avec les valeurs de l’épaisseur et du désaccord de maille attendus en moyenne. Néanmoins, de petites inclinaisons locales de mailles ont été observées - de l’ordre de 0.02°- et confirmées par modélisation numérique. Les résultats démontrent la sensibilité de la technique, ainsi que ses perspectives passionnantes pour l’imagerie des matériaux organiques et inorganiques nanostructurés complexes. / Ptychography is a coherent diffraction imaging technique which aims in retrieving the lost phase from intensity-only far-field measurements. The versatility of the approach has proved an important asset for 3D mapping of different physical quantities, like the electron density of micrometer-sized specimens with resolution in the 10 - 100nm range. In this work, we explored the possibility to push further the current limits of 3D Bragg ptychography, by addressing the case of an extended InP/InGaAs nanostructured thin film, bonded on a silicon wafer. The experiment was performed at the ID13 beamline at ESRF, with a monochromatic beam focused down to 100nm. 2D intensity patterns were acquired at several incidence angles in the vicinity of the InP (004) Bragg peak, stacking up a three dimensional dataset. Numerical analysis of the given problem was performed beforehand in order to optimize the inversion strategy and study the possibility of introducing additional physical constraints through regularization approaches. Inversions of the dataset were done using a ptychographical gradient-based optimization phase retrieval algorithm. The developed strategy was applied on the experimental data which led to the retrieval of a complex-valued 3D image. The result exhibits the high crystallinity quality of the sample with the expected values of thickness and lattice mismatch, nevertheless, small local lattice tilts have been observed - in the order of 0.02°- and confirmed by numerical modeling. This result demonstrates the high sensitivity of the technique, as well as its exciting perspectives for imaging complex organic and inorganic nanostructured materials.

We present Chandra and XMM-Newton X-ray, Very Large Array (VLA) radio, and optical observations of three candidate compact steep spectrum (CSS) radio galaxies. CSS sources are of a galactic scale and are presumably driving a shock through the interstellar medium (ISM) of their host galaxy. B3 1445+410 is a low-excitation emission line CSS radio galaxy with possibly a hybrid Fanaroff-Riley FRI/II (or fat double) radio morphology. The Chandra observations reveal a point-like source that is well fit with a power law consistent with the emission from a Doppler boosted core. 3C 268.3 is a CSS broad-line radio galaxy (BLRG) whose Chandra data are consistent spatially with a point source centered on the nucleus and spectrally with a double power-law model. PKS B1017-325 is a low-excitation emission line radio galaxy with a bent double radio morphology. While from our new spectroscopic redshift, PKS B1017-325 falls outside the formal definition of a CSS, the XMM-Newton observations are consistent with ISM emission with either a contribution from hot shocked gas or non-thermal jet emission. We compile selected radio and X-ray properties of the nine bona fide CSS radio galaxies with X-ray detections so far. We find that two out of the nine show X-ray spectroscopic evidence for hot shocked gas. We note that the counts in the sources are low and that the properties of the two sources with evidence for hot shocked gas are typical of the other CSS radio galaxies. We suggest that hot shocked gas may be typical of CSS radio galaxies due to their propagation through their host galaxies.

We present new evidence that the bright nonthermal X-ray emission features in the interior of the Cassiopeia A supernova remnant are caused by inward-moving shocks, based on Chandra and NuSTAR observations. Several bright inward-moving filaments were identified using monitoring data taken by Chandra in 2000-2014. These inward-moving shock locations are nearly coincident with hard X-ray (15-40 keV) hot spots seen by NuSTAR. From proper-motion measurements, the transverse velocities were estimated to be in the range of similar to 2100-3800 km s(-1) for a distance of 3.4 kpc. The shock velocities in the frame of the expanding ejecta reach values of similar to 5100-8700 km s(-1), which is slightly higher than the typical speed of the forward shock. Additionally, we find flux variations (both increasing and decreasing) on timescales of a few years in some of the inward-moving shock filaments. The rapid variability timescales are consistent with an amplified magnetic field of B similar to 0.5-1 mG. The high speed and low photon cut-off energy of the inward-moving shocks are shown to imply a particle diffusion coefficient that departs from the Bohm regime (k(0) = D-0/D-0,D-Bohm similar to 3-8) for the few simple physical configurations we consider in this study. The maximum electron energy at these shocks is estimated to be similar to 8-11 TeV, which is smaller than the values of similar to 15-34 TeV that were inferred for the forward shock. Cassiopeia A is dynamically too young for its reverse shock to appear to be moving inward in the observer frame. We propose instead that the inward-moving shocks are a consequence of the forward shock encountering a density jump of 5-8 in the surrounding material.

We present new Chandra observations of the outer halo of the giant elliptical galaxy NGC 4472 (M49) in the Virgo Cluster. The data extend to 130 kpc (28'), and have a combined exposure time of 150 ks. After identifying optical counterparts using the Next Generation Virgo Cluster Survey to remove background active galactic nuclei and globular cluster (GC) sources, and correcting for completeness, we find that the number of field low-mass X-ray binaries (LMXBs) per unit stellar V-band light increases significantly with the galactocentric radius. Because the flux limit of the complete sample corresponds to the Eddington limit for neutron stars in NGC 4472, many of the similar to 90 field LMXBs in this sample could host black holes. The excess of field LMXBs at large galactocentric radii may be partially caused by natal kicks on black holes and neutron stars in binary systems in the inner part of the galaxy. Furthermore, because the metallicity in the halo of NGC 4472 strongly decreases toward larger galactocentric radii, the number of field LMXBs per unit stellar mass is anticorrelated with metallicity, opposite to what is observed in GCs. Another way to explain the spatial distribution of field LMXBs is therefore a reversed metallicity effect, although we have not identified a mechanism to explain this in terms of stellar and binary evolution.

Mixed radiation fields, where different ionizing particles act together, are very important in radiobiology and in radiation protection. Mixed beams are not only the most common form of radiation exposure, but the prediction of their biological effect is also full of uncertainties. Currently, prediction of the biological damage of exposure to mixed radiation fields is based on the default assumption of simple additivity between the effects of all the radiation in the field. This assumption has been proven to be incorrect. Indeed, the simultaneous effect of different radiation qualities has been shown to be greater than additive, namely synergistic. This implicates that, for instance, the predicted cancer risk for astronauts, that remain a prolonged time in space, is currently underestimated as well as the risk of developing secondary cancer for radiotherapy patients. This thesis aims at understanding the mechanisms behind the cellular response to simultaneous exposure to alpha particles and X-rays (that is referred as mixed beam). Paper I describes the cell killing and the mutagenic effect of mixed beam exposure in human lymphoblastoid wild type and in cells with impaired capacity to repair oxidative DNA damage .We found that oxidative DNA damage plays an important role in the lethal, synergistic effect of mixed beams. Paper II and III investigates whether mixed beams exposure leads to an augmented DNA double strand breaks (DSB) induction or to an altered response of the cellular DSB repair machinery. We found that mixed irradiation resulted in synergistic induction of DSB, and that those lesions were repaired with slow kinetics. Paper IV focuses on the effect of mixed beams at the level of DNA damage in normal cells. Induction and repair of DNA lesions such as DSB, single strand breaks and apurinic sites was quantified using the alkaline comet assay. We found that alpha particles and X-rays interacted in inducing DNA damage. Moreover, although mixed beam exposure resulted in strong activation of the DNA damage response, it resulted in delayed repair. Although more research is needed to fully elucidate the mechanisms behind the detected synergistic effects, our results strongly suggest that an overwhelmed DNA-repair system causes delay in repair of damage. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Accepted. Paper 3: Manuscript. Paper 4: Manuscript.</p>

The ongoing development of storage devices and technologies for medical image management has led to a growth in the digital archiving of these images. The characteristics of medical x-rays are examined, and a number of digital coding methods are considered. An investigation of several fast cosine transform algorithms is carried out. An adaptive cosine transform coding technique is implemented which produces good quality images using bit rates lower than 0.38 bits per picture element

Dans le domaine de l'imagerie par rayons X, la course à la haute résolution mets aujourd'hui en évidence les limites des tubes actuels. Le béryllium utilisé pour fabriquer les fenêtres des tubes à rayons X ne permet pas de dissiper les densités de puissance mises en jeux. Cette thèse est le fruit d'une collaboration entre Thales et le Commissariat à l'Energie Atomique. Elle vise à étudier, concevoir et synthétiser des fenêtres innovantes en diamant pour les tubes à rayons X. Les propriétés de photoconduction du diamant sont utilisées pour intégrer une fonction de détection en ligne. Les fenêtres en transmission conçus dans le cadre de cette thèse sont appelées smart-window. En utilisant une approche multi-domaines, nous avons modélisé les phénomènes thermiques, mécaniques et de détection. Deux dispositifs différents en diamant polycristallin et monocristallin ont ainsi été conçus et dimensionnés. Pour intégrer ces fenêtres en situation expérimentale, une petite série doit être fabriquée. Ainsi, les conditions de synthèse ont été optimisées afin d'augmenter la vitesse de croissance du diamant. De nouveaux outils ont également été développés afin de suivre in situ la vitesse et la morphologie du film pendant cette croissance. Finalement, la résistance mécaniques et la transparence des fenêtres ont été caractérisées. Plusieurs bancs de test ont été développés pour tester leur fonction de détection en laboratoire. Différents prototypes de smart-windows ont été intégrés dans un tube expérimental. Ce prototype de fenêtre innovante en diamant délivre une mesure proportionnelle au débit de dose généré par le tube sans perturber son utilisation. / In the race towards high resolution X-ray imaging, the current X-ray windows have shown thermal limitations. The beryllium used in those windows does not provide an efficient spreading of the heat generated in the target. This thesis results from a collaboration between Thales and the french Atomic and Alternative Energies Commission (CEA). It aims at studying, designing and synthesizing innovative diamond for X-Ray tubes. The semi-conducting properties of diamond are used to integrate a built-in flow sensor and to monitor in-line the dose rate of the tube. The transmission windows fabricated in the context of this work are called “smart-windows”. The thermal, mechanical and sensing properties of such windows have been modeled by using a multi-domain approach. Two devices made either of polycrystalline or single crystal diamond were designed. In order to integrate those windows experimentally, a small series must be realized. Hence the experimental conditions have been optimized to increase the growth rate of the film. A new tools has also been developed to monitor in real time and in situ the growth rate and the morphology of the films. Finally the mechanical resistance and the transparency of the devices have been characterized. Several experimental set-ups have been developed to test the detection properties in a tube-like design. Some prototypes of smart-windows have been integrated in an experimental X-Ray tube. This prototype delivers a signal proportional to the dose rate of the tube without disturbing its operation.

Cette thèse porte sur le développement des méthodes d'analyse structurale de la couche mince de GaP epitaxiées sur le substrat de silicium par l'épitaxie par jets moléculaires (MBE), basées sur la diffraction des rayons X (ORX) et combinées à des techniques complémentaires telles que la microscopie électronique en transmission (TEM), la microscopie à force atomique (AFM) et la microscopie à effet tunnel (STM). Le travail est centré sur la caractérisation quantitative de la densité des défauts cristallins comme les micro-macles et les domaines d'inversion présents dans la couche ainsi que l'évaluation de la qualité de surface et l'interface. L'objectif ultime est d'obtenir une plate-forme GaP/Si parfaitement cristallisée sans défaut, via l'optimisation des paramètres de croissance. Nous avons mis en place et utilisé deux méthodes de quantification des micro-macles par la diffraction des rayons X en condition de laboratoire : les figures de pôles pour la visualisation rapide et l'évaluation de la densité des micro-macles et les « rocking-curves » permettent une extraction précise de la faction volumique de domaine maclé. Les propriétés structurales de la plate-forme de GaP/Si ont été considérablement améliorées, après une procédure d'optimisation impliquant la température de croissance, une procédure de croissance alternée (MEE) et une séquence de croissance en deux étapes. Un échantillon quasiment sans micro-macles a été obtenu par le dépôt de 40 monocouches de GaP par MEE à 350 •c suivi d'une surcroissance de 40 nm de GaP par MBE continue, à 500 •c. La surface de l'échantillon est lisse avec une rugosité de 0.3 nm. L'évaluation des domaines d'inversion par la ORX a été effectuée sur les cartographies de l'espace réciproque centrées sur les réflexions GaP de type (OOL), en laboratoire et sur une ligne synchrotron. Les balayages « transverses » extrait à partir des cartographies de l'espace réciproque sont analysés via une méthode dite "Williamson-Hall like", afin d'obtenir la "mosaïcité" qui est reliée à la micro-désorientation des petits domaines cristallins et la longueur de corrélation latérale correspondant à ces petits domaines. La distance moyenne entre parois de domaines d'inversion et ensuite estimé à partir de cette mesure. En utilisant cette méthode d'analyse et les techniques microscopiques, une optimisation plus poussée a été effectuée sur la dose de Ga au stade initial de croissance, l'utilisation de couches de marqueur AIGaP et l'homoépitaxie d'une couche de silicium avant le GaP. Enfin, nous avons obtenu un échantillon ne présentant pas de signal de micro-macle détectable en conditions standard de laboratoire, et une très faible densité de domaine d'inversion. Nous avons aussi observé une interface de GaP/Si visiblement présentant des bi-marches atomiques très régulières, sur un échantillon avec une couche de silicium déposée avant la croissance du GaP. / This thesis deals with the development of structural analysis methods of the GaP thin layers heterogeneously grown on the Si substrate by Molecular Beam Epixay (MBE), based on X-ray diffraction (XRD) analyses, combined with complementary techniques such as transmission electron microscopy (TEM), atomic force microscopy techniques (AFM) and scanning tunneling microscope (STM). The main work is centered on the quantitative characterization of crystalline defect such as micro-twins and the anti-phase domains, and the evaluation of the surface and interface quality. The ultimate goal is to achieve a perfectly crystallized GaP/Si platform without any defect, through the optimization of the growth conditions. We have applied two micro-twin quantification methods using a XRD lab setup. Pole figure method for fast visualization and evaluation of micro-twin density and rocking curves integration for a more precise absolute quantification of the micro-twin volume fraction. The GaP/Si platform structural properties have been significantly improved, after an optimization procedure involving growth temperature, MEE (Migration Enhanced Epitaxy) growth procedure and a twostep growth sequence. GaP layers quasi-free of MTs are obtained, with a r.m.s. roughness of only 0.3 nm. The APD evaluation by XRD has been performed on reciprocal space maps (RSM) centered on the (OOL) GaP reciprocal space lattice point either in lab setup or on synchrotron. Analysis of the transverse scans extracted from such RSM through the "Willamson-Hall like" method permits obtaining the "mosaicity" that is related to the micro-orientation of the small crystalline domains in the GaP layer, and the lateral correlation length which is considered to be related to the mean distance between two APBs, provided that this distance is approximately homogenous and corresponding to the mean APD size, and the density of other defects are very weak so that their influence can be neglected. Using this analytical method and the microscopic techniques, further optimization has been carried out on Ga amount at the initial growth stage, the use of AIGaP marker layers and the homoepitaxie of Si buffer layer. Finally, sample with none MT signal and very low density of APD has been achieved. Moreover, an abrupt GaP/Si interface displaying regular and double atomic steppes is observed on sample with a Si buffer layer prior to the GaP growth.

A direct consequence of hierarchical galaxy formation is the existence of dual supermassive black holes, which may be preferentially triggered as active galactic nuclei (AGNs) during galaxy mergers. Despite decades of searching, however, dual AGNs are extremely rare, and most have been discovered serendipitously. Using the all-sky WISE survey, we identified a population of over 100 morphologically identified interacting galaxies or mergers that display red mid-infrared colors often associated in extragalactic sources with powerful AGNs. The vast majority of these advanced mergers are optically classified as star-forming galaxies, which suggests that they may represent an obscured population of AGNs that cannot be found through optical studies. In this work, we present Chandra/ACIS observations and near-infrared spectra with the Large Binocular Telescope of six advanced mergers with projected pair separations less than similar to 10 kpc. The combined X-ray, near-infrared, and mid-infrared properties of these mergers provide confirmation that four out of the six mergers host at least one AGN, with four of the mergers possibly hosting dual AGNs with projected separations less than similar to 10 kpc, despite showing no firm evidence for AGNs based on optical spectroscopic studies. Our results demonstrate that (1) optical studies miss a significant fraction of single and dual AGNs in advanced mergers, and (2) mid-infrared pre-selection is extremely effective in identifying dual AGN candidates in late-stage mergers. Our multi-wavelength observations suggest that the buried AGNs in these mergers are highly absorbed, with intrinsic column densities in excess of similar to N-H > 10(24) cm(-2), consistent with hydrodynamic simulations.