centenares de keV hasta unos pocos MeV), presenta un extraordinario potencial para comprender los procesos más extremos que tienen lugar en el Universo, como las explosiones estelares o los aceleradores de partículas. No obstante, a pesar de los enormes esfuerzos realizados por los observatorios de rayos gamma (en el pasado y en la actualidad), se requiere una mejora en la sensibilidad instrumental para aprovechar el enorme potencial científico contenido en este rango energético. Durante las dos últimas décadas se han buscado formas de mejorar la sensibilidad de los instrumentos, incrementando la eficiencia de los detectores y reduciendo el ruido instrumental (mediante sofisticados mecanismos de blindaje y técnicas de análisis). Con este objetivo, un enorme esfuerzo en innovación instrumental (construcción de prototipos y estudios numéricos) está siendo realizado por una comunidad creciente de científicos que se enfrentan al reto de preparar la próxima generación de telescopios de rayos gamma. En particular, son especialmente notables los avances logrados en los últimos años en el campo de la focalización de rayos gamma mediante lentes de difracción. Conceptualmente, una lente de rayos gamma reduciría drásticamente el ruido instrumental ya que concentra los fotones en un detector de pequeñas dimensiones (el ruido es proporcional al volumen del instrumento). Una lente de difracción, para observaciones en astrofísica nuclear, no es sólo un concepto teórico, sino una realidad, gracias principalmente al proyecto CLAIRE. Asimismo, el desarrollo de la tecnología para la focalización de rayos gamma ha incentivado el desarrollo de las diferentes tecnologías de detección. Un detector apropiado para el plano focal de una lente gamma, debe disponer de capacidad de imagen, proporcionar espectroscopia de alta resolución y medir la polarización de los fotones incidentes. El trabajo presentado en esta tesis comprende tanto la óptica de focalización como el detector del plano focal. Con respecto a la óptica, se presenta el ensayo realizado con el prototipo CLAIRE, mediante el cual se ha confirmado los principios de una lente de difracción. En cuanto al plano focal, esta investigación se ha desarrollado principalmente en el marco de estudio de las misiones espaciales GRI (2007) y DUAL (2010), propuestas a la ESA dentro del programa “Cosmic Vision 2015-2025”. En el marco de la misión GRI, se presenta una configuración para el detector del plano focal basado en detectores pixelados de Cd(Zn)Te, al tiempo que se investiga y desarrolla un primer prototipo de detector pixelado de CdTe. Cabe destacar que el sistema de detección propuesto fue registrado con éxito mediante una patente europea, y está siendo desarrollado para su aplicación en medicina nuclear. En relación a la propuesta DUAL, se presenta un estudio del ruido instrumental obtenido mediante simulaciones numéricas con el fin de precisar la sensibilidad del instrumento (basado en detectores de Germanio) propuesto en esta misión. Más allá de las tecnología consideradas en GRI y DUAL, una amplia variedad de detectores pueden ser explorados, bien para el plano focal de una lente de difracción o bien como sistemas de detección por sí mismos. En este sentido, se ha ampliado el espectro de tecnologías y se ha incluido un estudio sobre detectores basados en xenón líquido. En esta tesis se ha realizado un trabajo de investigación y desarrollo con tecnologías vanguardistas propuestas para la próxima generación de telescopios de rayos gamma. Esta instrumentación debe enfrentarse al reto de alcanzar la sensibilidad requerida para dar respuesta a las cuestiones aun no resultas por la astrofísica de rayos gamma en el rango de energía de las transiciones nucleares. / few MeV) has an extraordinary potential for understanding the evolving and violent Universe. In spite of the strong efforts accomplished by past and current instruments, in order to perform observations in this energy range, an improvement in sensitivity over present technologies is needed to take full advantage of the scientific potential contained in this energy range. In order to achieve higher sensitivities, γ-ray astronomy has been looking over the last decades for new ways to increase the efficiency of its instruments while reducing the background noise. With the objective of reducing or avoiding as much background as possible (through shielding mechanisms and data analysis techniques), a strong effort in innovation and design (build-up of prototypes and numerical simulations studies) is being conducted by a community facing the challenge of preparing the next generation of γ-ray telescopes. In particular, the progress achieved during the last decade on focusing optics based on Laue lenses is especially remarkable. Conceptually, a focusing telescope will reduce drastically the background noise by concentrating γ-rays onto a small size detector. Focusing γ-rays with a Laue lens is not just a theoretical concept, but a reality, mainly thanks to the development of a first prototype of Laue lens for nuclear astrophysics accomplished as part of the CLAIRE project. Moreover, the development of focusing optics during these years has also encouraged the development of new detector technologies. The focal plane detector of a focusing telescope should provide imaging capabilities, perform high-resolution spectroscopy and measure the polarization of the incident photons in order to achieve the ambitious scientific goals. The research presented in this thesis covers both main areas of a γ-rays telescope: focusing optics and focal plane detector. As far as the optics is concerned, a test of the lens CLAIRE was performed in order to confirm the principles of a Laue diffraction lens. Concerning the focal plane detector, theoretical and experimental studies with new detector technologies have been carried out. Our main research has evolved in the framework of two mission concept studies -GRI (2007) and DUAL (2010)- submitted to the ESA Calls for a Medium-size mission opportunity within the Cosmic Vision 2015-2025 program. As far as the GRI mission is concerned, a focal plane detector configuration based on Cd(Zn)Te pixelated detectors is proposed, whilst development and testing of a detector prototype is accomplished. It is noteworthy that the detector configuration was successfully registered under a European Patent and is being considered for applications in the field of nuclear medicine. Regarding the DUAL mission, simulations of the expected space radiation environment and the resulting detector activation were carried out in order to estimate the performances of the all-sky Compton telescope of DUAL (based on Germanium-strip detectors). The results show that DUAL could achieve, after two years of operation, a continuum sensitivity one order of magnitude better than any past and current observatory in the MeV energy range and up to a factor 30 of improvement with its Laue lens. Beyond the detector technology proposed for GRI and DUAL, a wide variety of technologies could be explored for the focal plane of a γ-ray lens mission as well as for a stand-alone detector. In this thesis a focal plane detector based on liquid xenon is also considered. This work faces the challenges of the next generation of γ-ray telescopes, where high performance γ-ray detectors are necessary to achieve the required sensitivity in order to answer several hot scientific topics of Gamma-ray astrophysics in the energy range of nuclear transitions.

In order to monitor a nuclear boiling water reactor fixed and movable detectors are used, such as the neutron sensitive LPRM (Local Power Range Monitors) detectors and the gamma sensitive TIP (Traversing Incore Probe) detectors. These provide a mean to verify the predictions obtained from core simulators, which are used for planning and following up the reactor operation. The core simulators calculate e.g. the neutron flux and power distribution in the reactor core. The simulators can also simulate the response in the LPRM and TIP detectors. By comparing with measurements the accuracy of the core simulators can be quantified. The core simulators used in this work are PHOENIX4 and POLCA7. Because of the complexity of the calculations, each fuel assembly is divided axially into typically 25 nodes, which are more or less cubic with a side length of about 15 cm. Each axial segment is simulated using a 2D core simulator, in this work PHOENIX4, which provides data to the 3D code, in this case POLCA7, which in turn perform calculations for the whole core. The core simulators currently use both radial pin weights and axial node weights to calculate the gamma TIP detector signal. A need to bring forward new weight factors has now been identified because of the introduction of new fuel designs. Therefore, the gamma TIP detector response has been simulated using a Monte Carlo code called MCNPX for a modern fuel type, SVEA-96 Optima2, which is manufactured by Westinghouse. The new weights showed some significant differences compared to the old weights, which seem to overestimate the radial weight of the closest fuel pins and the axial weight of the node in front of the detector. The new weights were also implemented and tested in the core simulators, but no significant differences could be seen when comparing the simulated detector response using new and old weights to authentic TIP measurements.

In recent years, there have been several research endeavors to increase the ability to identify and quantify special nuclear material in field measurements. These have included both gamma spectroscopy and neutron coincidence systems that are portable and work in a variety of environments. In this work, a Monte Carlo Neutral Practicle X (MCNPX) model was used to design an instrument that includes four gamma detection slabs placed within four neutron detection slabs. The combination of gamma spectroscopy and neutron coincidence counting in a single instrument allows for direct measurement of plutonium (Pu) mass without need for assumptions or operator declarations. A combined neutron-gamma instrument was designed for use in characterizing and quantifying Pu in field samples. This detector consists of a plastic scintillator containing LaBr3 nanoparticles and a polyethylene slab containing four 3He tube detectors. The system was tested via simulation with MCNPX for four Pu samples of known quality and quantity. These samples had masses ranging from 100-300 g of Pu. It was found that the designed detector system could be used to determine 240Pu-effective mass to within 3.5% accuracy and to characterize the isotopic content of the Pu to within 2% accuracy for all isotopes except for 238Pu and 242Pu. The system could determine 238Pu isotopic content to within 14% accuracy but is completely unable to determine 242Pu content. This system has the ability to Four Plutonium (Pu) samples of known quantity were modeled and tested to determine what data was available from each individual signature. Each model included a separate MCNPX deck for each individual isotope that contributes to the gamma signature in photon mode and a spontaneous fission and (alpha,n) deck for the neutron signature. The first three samples were used to create spectrums and efficiency curves for each odd isotope as well as for a Pu effective mass for the neutron signature. The data from these simulations were then used to identify the isotopics in the fourth sample to within acceptable accuracy. From this data, a total Pu mass was obtained as well as an ability to determine the ratio of (alpha,n) to spontaneous fission neutrons without additional simulations. This provides a new method to detect and identify the Pu content within a sample without producing requiring supplemental additional information since isotopics can be determined with the combined use of the gamma and neutron systems.

The chaperone proteins designated 14-3-3 are expressed in all eukaryotic cells; they help to regulate signal transduction pathways controlling proliferation, differentiation, and survival. They associated directly or indirectly with proliferative signal-transducing proteins such as PKC, MEK kinases, PI3-kinase and Raf. In human, there are seven isotypes of 14-3-3 genes: £]¡]beta¡^¡B£^¡]gamma¡^¡B£`¡]epsilon¡^¡B£b¡]eta¡^¡B£m¡]sigma¡^¡B£n/£c¡]tau/theta¡^ and£a¡]zeta¡^, some of which would be pseudogenes, and yeast and plant each have two and fifteen genes. Althought these genes are diverse, all 14-3-3 isotypes share many conservation domains in amino acid sequences. The previous studies have suggested that 14-3-3 sigma is most directly linked to cancer because it is thought to function as a tumor suppressor by inhibiting cell-cycle progression. In tumor formation, inactivation of 14-3-3 sigma occurs with high frequency. More importantly, expression of 14-3-3 sigma is silenced in most breast cancer cells. The 14-3-3 sigma protein is associated with cyclin E-CDK2 complex as well as cyclin B-CDC2 complex and mediated their inactivation by cytoplasmic localization and causing cell-cycle arrest in G2 and G1. However, the roles of other 14-3-3 isotypes in the formation of breast cancer are controversial in published reference. The aim of this study was to determine the differential expressions of 14-3-3 gamma in non-tumor tissues and corresponding tumor tissues. Amplification and overexpression of 14-3-3 gamma in DNA, RNA, and protein of breast tumor tissues were found by experiments of RT-PCR, Western blot analysis, immunohistochemistry and Real-time PCR. However, the role of 14-3-3 gamma in the formation of breast cancer requires further study.

Thèse de doctorat--Géologie--Grenoble 1, 2004. / Bibliogr. p. 140-143 p. Résumé en français et en anglais.

Reproduction de : Thèse de doctorat : Astrophysique : Toulouse 3 : 2007. / Titre provenant de l'écran-titre. Bibliogr. à la fin des chapitres.

Thesis (M.S.)--California Polytechnic State University, 2009. / Title from PDF title page; viewed on January 13, 2010. Major professor: William Ahlgren, Ph.D. "Presented to the Electrical Engineering faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in Electrical Engineering." "December 2009." Includes bibliographical references (p. 81-87).

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves [86]-88).

The large flashes of radiation that are observed in GRBs are generally believed to arise in a relativistic jetted outflow. This thesis addresses the question of how and where in the jet this radiation is produced. It further explores the jet properties that can be inferred from the observations made by the Fermi GST that regularly observes GRBs in the range 8 keV - 300 GeV.  In my analysis I focus on the observational effects of the emission from the jet photosphere. I show that the photosphere has an important role in shaping the observed radiation spectrum and that its manifestations can significantly vary between bursts. For bursts in which the photospheric  emission component can be identified, the dynamics of the flow can be explored by determining the  jet Lorentz factor and the position of the jet nozzle. I also develop the theory of how to derive the properties of the outflow for general cases. The spectral analysis of the strong burst GRB110721A reveals a two-peaked spectrum, with the peaks evolving differently. I conclude that three main flow quantities can describe the observed spectral behaviour in bursts:  the luminosity, the Lorentz factor, and the nozzle radius. While the photosphere can appear like a pure blackbody it can also be substantially broadened, due to dissipation of the jet energy below the photosphere. I show that Comptonisation of the blackbody can shape the observed spectra and describe its evolution. In particular this model can very well explain GRB110920A which has two prominent breaks in its spectra.  Alternative models including synchrotron emission leads to severe physical constraints, such as the need for very high electron Lorentz factors, which are not expected in internal shocks. Even though different manifestations of the photospheric emission can explain the data, and lead to ambiguous interpretations, I argue that dissipation below the photosphere is the most important process in shaping the observed spectral shapes and evolutions. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: In press. Paper 5: Submitted.</p>

The human mitochondrial polymerase (pol γ) is a nuclearly-encoded polymerase that is solely responsible for the faithful replication and repair of the mitochondrial genome. The Y955C mutation in pol γ results in early onset progressive external ophthalmoplegia, premature ovarian failure, and Parkinson’s disease. It is believed that the position of this Y955 residue on the catalytic helix in the polymerase makes it responsible for stabilizing the incoming nucleotide. I have investigated the kinetic effect of the Y955C mutation. Mutation of the tyrosine to a cysteine resulted in a decreased maximum rate of polymerization and increased the dissociation constant for incoming nucleotide. In turn, this decreased catalytic efficiency by 30 to 100-fold. In addition, the polymerase did not incorporate all bases with the same efficiency, it was most efficient when incorporating dGTP opposite a dC, but showed less efficient catalysis when faced with an A:T or T:A base-pair. The polymerase also showed reduced discrimination against misincorporation events. However, when presented with an oxidatively-damaged base, 8-oxo-deoxyguanosine, the polymerase chose to incorporate the base in the correct conformation opposite a dC, discriminating against the mutagenic incorporation of 8-oxo-dGTP opposite a dA. The results presented in this thesis suggest that the severe clinical symptoms of patients with this mutation are at least due in part to the reduced efficiency and discrimination of this polymerase γ mutation. / text