La TSPO préalablement connue sous le nom de récepteur périphérique aux benzodiazépines (PBR), est une protéine membranaire principalement impliquée dans le transport du cholestérol du cytosol vers la matrice des mitochondries, étape limitante dans la synthèse des stéroïdes et des sels biliaires.La production de la forme murine de la TSPO recombinante a été réalisée par un plasmide exprimé dans la bactérie Escherichia coli. La purification a été obtenue par colonne d'affinité grâce à l'étiquette polyhistidine codée dans le gène recombinant. Différents environnements mimétiques membranaires, détergents, lysodérivés, lipides ont été testés d'un point de vue structural et fonctionnel. Parmi les détergents étudiés, la dodécyl phosphocholine (DPC) a permis le meilleur repliement de la protéine. L'ajout de lysodérivés (LMPE) ou de phospholipides (DMPC/DMPE) a permis d'accroître la stabilité. La liaison des ligands spécifiques de la TSPO (PK 11195, cholestérol, protoporphyrine IX) a été observée dans plusieurs conditions étudiées par différentes approches biophysiques et biochimiques. Les trois approches structurales (ME, RX et RMN) ont pu être réalisées après optimisation des conditions de production et de stabilisation. Les résultats obtenus sont discutés en lien avec la structure de la TSPO publiée ces derniers mois. En parallèle à l'étude structurale, des mesures fonctionnelles par mutagenèse dirigée ont été réalisées afin d'obtenir des informations sur la liaison du ligand PK 11195. Ces données ont été confrontées à la structure récemment déterminée permettant de proposer un rôle pour les résidus mutés. Le mécanisme de transport du cholestérol par la TSPO est discuté. / TSPO previously named peripheral-type benzodiazepine receptor (PBR) is a membrane protein mostly involved in cholesterol transport from the cytosol to the matrix of mitochondria, a limiting step in steroids and bile salts biosynthesis.Production of recombinant mouse TSPO has been performed by plasmid expression in Escherichia coli bacteria. Purification has been obtained by immobilized affinity chromatography (IMAC) using polyhistidine tag encoded by recombinant gene. Various membranous mimetic environments such as detergents, lysoderivates, lipids have been tested from structural and functional point of view. Among tested detergents, dodecyl phosphocholine (DPC) has permitted the best protein refolding. The presence of lysoderivate (LMPE) or phospholipids (DMPC/DMPE) increased protein stability. Binding of TSPO high affinity ligands (PK 11195, cholesterol, protoporphyrin IX) has been measured in different conditions studied by biochemical and biophysical techniques. Three structural approaches (EM, XR and NMR) have been performed after optimization of production conditions and protein stabilization. Results gained have been discussed in line with TSPO atomic structure published within these last months. In parallel with structural studies, functional measurements have been carried out by site directed mutagenesis in order to gain data on binding site of PK 11195. These data have been faced with recently published TSPO atomic structure stabilized with this ligand and enabled to propose functional implication of mutated amino acids. Transport mechanism of cholesterol by TSPO is discussed.

An accurate and computationally fast method to generate nodal cross sections for the Pebble Bed Reactor (PBR) was presented. In this method, named Spectral History Correction (SHC), a set of fine group microscopic cross section libraries, pre-computed at specified depletion and moderation states, was coupled with the nodal nuclide densities and group bucklings to compute the new fine group spectrum for each node. The relevant fine group cross-section library was then recollapsed to the local broad group cross-section structure with this new fine group spectrum. This library set was tracked in terms of fuel isotopic densities. Fine group modulation factors (to correct the homogeneous flux for heterogeneous effects) and fission spectra were also stored with the cross section library. As the PBR simulation converges to a steady state fuel cycle, the initial nodal cross section library becomes inaccurate due to the burnup of the fuel and the neutron leakage into and out of the node. Because of the recirculation of discharged fuel pebbles with fresh fuel pebbles, a node can consist of a collection of pebbles at various burnup stages. To account for the nodal burnup, the microscopic cross sections were combined with nodal averaged atom densities to approximate the fine group macroscopic cross-sections for that node. These constructed, homogeneous macroscopic cross sections within the node were used to calculate a numerical solution for the fine group spectrum with B1 theory. This new fine spectrum was used to collapse the pre-computed microscopic cross section library to the broad group structure employed by the fuel cycle code. This SHC technique was developed and practically implemented as a subroutine within the PBR fuel cycle code PEBBED. The SHC subroutine was called to recalculate the broad group cross sections during the code convergence. The result was a fast method that compared favorably to the benchmark scheme of cross section calculation with the lattice cross-section generator for two PBR reactor designs.

Made available in DSpace on 2014-06-12T15:57:17Z (GMT). No. of bitstreams: 2 arquivo3157_1.pdf: 3737373 bytes, checksum: 7ca491f9a72f2e9cf51764a7acac3e3c (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2010 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Esta dissertação introduz uma estrutura de dados baseada em gride implementada em GPU. Ela foi desenvolvida para pesquisa dos vizinhos mais próximos em nuvens de pontos dinâmicas, de uma forma massivamente paralela. A implementação possui desempenho em tempo real e é executada em GPU, ambas construção do gride e pesquisas dos vizinhos mais próximos (exatos e aproximados). Dessa forma, a transferência de memória entre sistema e dispositivo é minimizada, aumentando o desempenho de uma forma geral. O algoritmo proposto pode ser usado em diferentes aplicações com cenários estáticos ou dinâmicos. Além disso, a estrutura de dados suporta nuvens de pontos tridimensionais e dada sua natureza dinâmica, o usuário pode mudar seus parâmetros em tempo de execução. O mesmo se aplica ao número de vizinhos pesquisados. Uma referência em CPU foi implementada e comparações de desempenho justificam o uso de GPUs como processadores massivamente paralelos. Em adição, o desempenho da estrutura de dados proposta é comparada com implementações em CPU e GPU de trabalhos anteriores. Finalmente, uma aplicação de renderização baseada em pontos foi desenvolvida de forma a verificar o potencial da estrutura de dados

The goal of this thesis is to create a graphics intro using the OpenGL library, where the maximal size of the executable is 64 kB. The program is written in C++ language and uses OpenGL version 4.6.

Today a lot of libraries, tools and techniques exist to create visual appealing renders for the web. In this thesis, a prototype for visualizing baseboards in the web browser was developed. The prototype demonstrates how certain libraries and techniques were used in order to achieve a generalized, appealing and realistic visualization of the baseboards in a 3D-visualization. This paper also covers why certain libraries and techniques were used for this prototype. The resulting prototype, use Three.js and takes advantage of PBR, different mapping methods and lighting sources that can be changed during runtime through a GUI. To get results on different aspects, such as the visual appeal, how realistic, and what lighting sources worked best for the prototype, a web-survey was sent out and the results evaluated. The evaluation showed that the usage of PBR, a roughness-metalness workflow, environment mapping, physical correct lighting and a point light solution in Three.js all made a good job in creating an appealing, generalized and realistic visualization tool for the web.

This dissertation introduces two novel techniques, OSF and PBR, to improve the performance of Sparse Matrix-vector Multiply (SMVM) kernels, which dominate the runtime of iterative solvers for systems of linear equations. SMVM computations that use sparse formats typically achieve only a small fraction of peak CPU speeds because they are memory bound due to their low flops:byte ratio, they access memory irregularly, and exhibit poor ILP due to inefficient pipelining. We particularly focus on improving the flops:byte ratio, which is the main limiter on performance, by exploiting recurring structures or sub-structures in matrices. Our techniques also support micro-architecture level optimizations to further improve performance. Operation Stacking Framework (OSF) stacks problems in large ensemble computations, which run the same sparse kernel using an identical matrix structure, such that they share a single copy of the indexing information to significantly reduce memory bandwidth usage. OSF provides performance improvements of up to 1.94x on an AMD Opteron compared to the CSR method. We validate performance results using hardware event counters, which demonstrate significantly improved cache and pipeline utilization. Pattern-based Representation (PBR) exploits recurring block nonzero patterns by generating custom code for each recurring block pattern. In this way, no indexing data for individual nonzero elements are read from memory, reducing the overall size of the indices by up to 98%. Our code generator emits highly tuned codes that utilize SSE vectorization and software prefetching. PBR accurately identifies a block size that achieves optimal or near-optimal performance using a linear multiple regression performance model. On recent multicore machines, PBR provides performance improvements of up to 3.4x sequentially and 5x in parallel, compared to the CSR method. The PBR library we provide converts matrices at runtime, allowing our method to be used as a drop-in replacement for existing methods. We compare PBR's overhead relative to its benefits and show that PBR is beneficial for many applications that repetitively call the SMVM kernel for the same matrix structure. / Ph. D.

No description available.

This report presents an exhibition all steps taken to implement a Laboratory of Plant Repairs Phone Cards. First are listed the issues that are missing from a laboratory to repair cards ATT call center technology. And no time to meet orders and preventive maintenance improvements and corrective. The lab is available to repair, diagnose and maintain the various cards that use technology call centers ATT - 5ESS. Besides being the burden that has more power, approximately 65% of full capacity at the national level. It also is taken into account the degree of quality of repairs and improvements to be made. Taking control and labeling of the cards and man hours worked, why are never short of supplies. Also be taken into account repair costs and inconvenience we have with the provider. And they must take into account the backs of phone cards have to be central in stock to operate smoothly and efficiently. At the end of this report presents recommendations and conclusions of the achievements in implementing this laboratory for repairs. Report called: “Operation, Repair and Maintenance of Central Telephone Cards” / Este informe expositivo presenta todos los pasos seguidos para poner en funcionamiento un Laboratorio de Reparaciones de Tarjetas de Centrales Telefónicas. Primero se enumeran las problemáticas que se tienen por falta de un laboratorio para reparar tarjetas de centrales telefónicas de tecnología ATT. Y no poder atender a tiempo los pedidos y mejoras de mantenimiento preventivo y correctivo. Dicho laboratorio se encargara de Reparar, Diagnosticar y dar Mantenimiento a las diferentes tarjetas que usan las Centrales Telefónicas de tecnología ATT - 5ESS. Además de ser la que tiene más carga de centrales, aproximadamente el 65% de toda su capacidad a nivel nacional. .Así mismo se tomara en cuenta el grado de calidad de las reparaciones y las mejoras a hacerse .Llevando un control y etiquetado de las tarjetas y horas hombre trabajadas, para qué nunca estén desabastecidas. Además se tomará en cuenta los costos de reparación y los inconvenientes que se tienen con el proveedor. Y se debe tener en cuenta los respaldos de tarjetas telefónicas de centrales que deban de tener en almacén para operar en forma ordenada y eficiente. Al final de este informe se presentan recomendaciones y conclusiones de lo realizado en la implementación de este laboratorio de Reparaciones. Informe que denominamos: “Operación, Reparación y Mantenimiento de Tarjetas de Centrales Telefónicas”

Le glioblastome représente le grade le plus élevé des tumeurs cérébrales. Sa croissance est favorisée par une forte néovascularisation de même que par l'activation de la voie du récepteur à l'EGFR-Ras. La première partie montre l'effet antiangiogénique et antitumoral de l'extrait de cartilage dans plusieurs modèles de glioblastome chez la souris. L'étude du transcriptôme des cellules endothéliales a permise de proposer des mécanismes d'actions. Il a été proposé que l'extrait de cartilage induise la sécrétion de cytokines, qui entraînent la génération de dérivés réactifs de l'oxygène. Ceux-ci entraîneraient l'activation du NFkB qui induirait l'expression d'un premier réseau de gènes impliqués dans l'inflammation de l'endothélium en croissance. La co-administration de corticoïdes pour réduire l'œdème tumoral a d'ailleurs entraîné une perte de l'efficacité in vivo et serait donc à proscrire en clinique. L'extrait de cartilage a également surexprimés un second réseau de gènes impliqués dans la protéolyse de la matrice, nécessaire à la stabilisation du tube vasculaire. Le rôle essentiel joué par l'activateur tissulaire du plasminogène (tPA) a été démontré par une étude fonctionnelle complète du système fibrinolytique in vivo. Enfin, la formation d'œdème tumoral, causé par ce système, a pu être contrôlée grâce à un co-traitement au N-actétylcystéine, ce qui a augmenté significativement la survie dans le modèle de glioblastome intracérébral chez la souris. Ce co-traitement serait recommandé pour des essais cliniques. La seconde partie montre que l'effet du TLN-4601 dépend d'une exposition chronique, ce qui a permis d'orienter le régime thérapeutique lors des essais cliniques. Il a été montré que ce dibenzodiazépines farnésylé, pouvait agir sur le récepteur périphérique des benzodiazépines (PBR) et les messagers farnésylés tel que Ras, Raf et Rho, dans la voie de l'EGFR. L'accumulation du composé dans les tumeurs, les effets sur la stéroïdogénèse et la dépolarisation de la mitochondrie, seraient attribuables au PBR. L'induction de tout un réseau de gènes responsables du catabolisme du glycérol et de la beta oxydation des acides gras, enlèverait les substrats nécessaires à la synthèse des phospholipides membranaires et la croissance des cellules tumorales. Ce changement métabolique, pourrait découler de l'inhibition d'Akt en aval de Ras. C'est pourquoi, les patients présentant les mutations de MDM2, p53 et PTEN, fréquemment rencontrées dans les GBM, ne seraient en théorie pas de bons candidats, car elles sont capables d'activer la voie de RAS en aval de l'effet du TLN. En revanche, la surexpression du PBR serait tout à fait souhaitable.

Svensk patenträtt har i stor omfattning harmoniserats med praxis utvecklad av det europeiska patentverket (EPO), vad avser patenterbarhetskriterier. Anledningen till harmoniseringen har motiverats av att det ska bli en mer enhetlig bedömning av patent i Europa. Harmoniseringen har i vart fall inte innefattat så kallad formell praxis, som innefattar regler om hand­läggandet hos det svenska patentverket, i förhållande till handläggandet av det vid EPO.   Vid Sveriges anslutning till European Patent Convention (EPC) år 1978, förespråkades att det svenska patentverket ansågs hålla en godtagbar standard i sin handläggning, men att det fram­tida förhållandet mellan svensk patenträtt och EPC kunde komma att innebära förändring om kvalitetsnivån inte kunde anses tillräcklig hög. Efter ett nyligen taget beslut av Patentbesvärsrätten (PBR) har Patent- och registreringsverkets (PRV) handläggning ifrågasatts, varför författarna valt att undersöka om en förändring av hand­läggningen vid PRV bör genomföras, i enlighet med det förslag som framställs i proposition 1977/78:1, med beaktande av praxis utvecklad av EPO.   I uppsatsen redogörs för hur EPO har tydligare regler avseende patent­ärenden än vad PRV har, varför en harmonisering av detta område bör diskuteras för säkerställandet av hög kvalitet vid handläggningen hos det svenska patentverket. Det är författarnas uppfattning att en ofullständig harmonisering även av formella regler resulterar i ett problem för säkerställandet av rättssäkerheten, eftersom lagregleringen i Sverige kan anses bristfällig. Således är det av intresse för svensk patenträtt att ta hänsyn till formell praxis utvecklad av EPO, alternativt, genom lagstiftningsförfarande, reglera bristen av tydliga regler.