The launch of the Large Area Telescope (LAT), on board the Fermi spacecraft, has led to an astounding increase in the number of known y-ray pulsars. This wealth of new data has generated renewed interest in the field of pulsar astrophysics, with many of the established geometric models for y-ray emission coming under fresh scrutiny. In this work the outer gap (OG) and two-pole caustic (TPC) geometric -ray models are employed alongside a simple empirical radio model to obtain best-fit light curves by eye for six single-peak Fermi LAT pulsars first reported by Weltevrede et al. (2010). These best-fit solutions aim to reproduce both the shapes of the radio and y-ray light curves, and the radio-to- phase lag. A parameter study of the geometric models is also conducted, and the increased qualitative understanding of these models thus gained is then employed to obtain the best fits possible. The combination of radio and -ray models is found to be remarkably powerful in constraining the values of the geometric parameters of the individual pulsars: the inclination and observer angles. Generally the constraints implied by the radio model act perpendicularly to those implied by the y-ray models, thus yielding smaller solution contours. The constraints on the geometric parameters obtained for the six Fermi LAT pulsars in question agree quite well with those obtained by Weltevrede et al. (2010). This agreement is remarkable considering that the approach employed in this study is independent from the one employed by Weltevrede et al. (2010). The errors obtained in this study on the values of the inclination angle for each pulsar are generally smaller than those obtained by Weltevrede et al. (2010). As a secondary result, the value of the flux correction factor, which is a measure of how well the observed y-ray energy flux of the pulsar correlates with the overall y-ray energy flux, is constrained for each pulsar. / MSc (Space Physics), North-West University, Potchefstroom Campus, 2014

The launch of the Large Area Telescope (LAT), on board the Fermi spacecraft, has led to an astounding increase in the number of known y-ray pulsars. This wealth of new data has generated renewed interest in the field of pulsar astrophysics, with many of the established geometric models for y-ray emission coming under fresh scrutiny. In this work the outer gap (OG) and two-pole caustic (TPC) geometric -ray models are employed alongside a simple empirical radio model to obtain best-fit light curves by eye for six single-peak Fermi LAT pulsars first reported by Weltevrede et al. (2010). These best-fit solutions aim to reproduce both the shapes of the radio and y-ray light curves, and the radio-to- phase lag. A parameter study of the geometric models is also conducted, and the increased qualitative understanding of these models thus gained is then employed to obtain the best fits possible. The combination of radio and -ray models is found to be remarkably powerful in constraining the values of the geometric parameters of the individual pulsars: the inclination and observer angles. Generally the constraints implied by the radio model act perpendicularly to those implied by the y-ray models, thus yielding smaller solution contours. The constraints on the geometric parameters obtained for the six Fermi LAT pulsars in question agree quite well with those obtained by Weltevrede et al. (2010). This agreement is remarkable considering that the approach employed in this study is independent from the one employed by Weltevrede et al. (2010). The errors obtained in this study on the values of the inclination angle for each pulsar are generally smaller than those obtained by Weltevrede et al. (2010). As a secondary result, the value of the flux correction factor, which is a measure of how well the observed y-ray energy flux of the pulsar correlates with the overall y-ray energy flux, is constrained for each pulsar. / MSc (Space Physics), North-West University, Potchefstroom Campus, 2014

Submitted by PPG Ci?ncia da Computa??o (ppgcc@pucrs.br) on 2017-11-13T21:02:54Z No. of bitstreams: 1 Felipe_Gohring_de_Magalh?es_TES.pdf: 7728697 bytes, checksum: f2b34275e49f32253d8c38848a3d9258 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-11-21T12:14:27Z (GMT) No. of bitstreams: 1 Felipe_Gohring_de_Magalh?es_TES.pdf: 7728697 bytes, checksum: f2b34275e49f32253d8c38848a3d9258 (MD5) / Made available in DSpace on 2017-11-21T12:26:58Z (GMT). No. of bitstreams: 1 Felipe_Gohring_de_Magalh?es_TES.pdf: 7728697 bytes, checksum: f2b34275e49f32253d8c38848a3d9258 (MD5) Previous issue date: 2017-05-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / As tend?ncias de design para os sistemas multiprocessadores da pr?xima gera??o apontam para a integra??o de um grande n?mero de n?cleos de processamento, exigindo interconex?es de alto desempenho. Uma solu??o a ser aplicada para melhorar a infraestrutura de comunica??o em tais sistemas ? o uso de redes on-chip, pois estas apresentam uma melhoria consider?vel na largura de banda e escalabilidade. Ainda assim, o n?mero de n?cleos integrados continua a aumentar ao mesmo tempo em que o sistema cresce, dessa maneira as interconex?es met?licas em redes on-chip podem tornar-se um gargalo no desempenho. Como resultado, uma nova estrat?gia deve ser adotada para que essas quest?es sejam solucionadas. As Redes ?pticas Integradas (do ingl?s Optical Integrated Networks - OINs) s?o atualmente consideradas como um dos paradigmas mais promissores neste contexto de design: elas apresentam maior largura de banda, menor consumo de energia e baixa lat?ncia para transmitir informa??es. Al?m disso, trabalho recentes demonstram a viabilidade de OINs com suas tecnologias de fabrica??o dispon?veis e compat?veis com CMOS. No entanto, os designers de OINs enfrentam v?rios desafios: ? Atualmente, os controladores representam o principal gargalo na comunica??o e s?o um dos fatores que limitam o uso de OINs. Portanto, novas solu??es de controle de baixa lat?ncia s?o necess?rias. ? Designers n?o possuem ferramentas para modelar e validar OINs. A maioria das pesquisas atualmente est? focada em projetar dispositivos e melhorar os componentes b?sicos, deixando o sistema sem melhorias. Neste contexto, para facilitar a implanta??o de sistemas baseados em OIN, este projeto de doutorado concentra-se em tr?s contribui??es principais: (1) o desenvolvimento da plataforma de simula??o a n?vel de sistema; (2) a defini??o e o desenvolvimento de uma abordagem de controle eficiente para sistemas baseados em OIN e; (3) a avalia??o, a n?vel do sistema, da abordagem de controle proposta usando a modelagem definida. / Design trends for next-generation Multi-Processor Systems point to the integration of a large number of processing cores, requiring high-performance interconnects. One solution being applied to improve the communication infrastructure in such systems is the usage of Networkson- Chip as they present considerable improvement in the bandwidth and scaleability. Still as the number of integrated cores continues to increase and the system scales, the metallic interconnects in Networks-on-Chip can become a performance bottleneck. As a result, a new strategy must be adopted in order for those issues to be remedied. Optical Integrated Networks (OINs) are currently considered to be one of the most promising paradigm in this design context: they present higher bandwidth, lower power consumption and lower latency to broadcast information. Also, the latest work demonstrates the feasibility of OINs with their fabrication technologies being available and CMOS compatible. However, OINs? designers face several challenges: ? Currently, controllers represent the main communication bottleneck and are one of the factors limiting the usage of OINs. Therefore, new controlling solutions with low latency are required. ? Designers lack tools to model and validate OINs. Most research nowadays is focused on designing devices and improving basic components performance, leaving system unattended. In this context, in order to ease the deployment of OIN-based systems, this PhD project focuses on three main contributions: (1) the development of accurate system-level modelling study to realize a system-level simulation platform; (2) the definition and development of an efficient control approach for OIN-based systems, and; (3) the system-level evaluation of the proposed control approach using the defined modelling.

<p>Stimulation of the T cell receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins, leading to activation of the interleukin-2 (IL-2) gene in T lymphocytes. Shb is a ubiquitously expressed adapter protein, with the ability to associate with the T cell receptor and several signaling proteins in T cells, including: the TCR ζ-chain, LAT, PLC-γ1, Vav, SLP-76 and Gads. Jurkat T cells expressing Shb with a mutation in the SH2 domain, exhibited reduced phosphorylation of several proteins and abolished activation of the MAP kinases ERK1, ERK2 and JNK, upon CD3 stimulation. The TCR induced Ca²⁺ response in these cells was abolished, together with the activation of the IL-2 promoter via the transcription factor NFAT. Consequently, IL-2 production was also perturbed in these cells, compared to normal Jurkat T cells. Shb was also seen to associate with the β and γ chains of the IL-2 receptor, upon IL-2 stimulation, in T and NK cells. This association occurred between the Shb SH2 domain and Tyr-510 of the IL-2R β chain. The proline-rich domains of Shb were found to associate with the tyrosine kinases JAK1 and JAK3, which are important for STAT-mediated proliferation of T and NK cells upon IL-2 stimulation. Shb was also found to be involved in IL-2 mediated regulation of apoptosis. These findings indicate a dual role for Shb in T cells, where Shb is involved in both T cell receptor and IL-2 receptor signaling. </p><p>A Shb homologue, Shf was identified, and seen to associate with the PDGF-α-receptor. Shf shares high sequence homology with Shb and a Shd (also of the Shb family) in the SH2 domain and in four motifs containing putative tyrosine phosphorylation sites. When Shf was overexpressed in fibroblasts, these cells displayed significantly lower rates of apoptosis than control cells in the presence of PDGF-AA. These findings suggest a role for the novel adapter Shf in PDGF-receptor signaling and regulation of apoptosis.</p>

Stimulation of the T cell receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins, leading to activation of the interleukin-2 (IL-2) gene in T lymphocytes. Shb is a ubiquitously expressed adapter protein, with the ability to associate with the T cell receptor and several signaling proteins in T cells, including: the TCR ζ-chain, LAT, PLC-γ1, Vav, SLP-76 and Gads. Jurkat T cells expressing Shb with a mutation in the SH2 domain, exhibited reduced phosphorylation of several proteins and abolished activation of the MAP kinases ERK1, ERK2 and JNK, upon CD3 stimulation. The TCR induced Ca2+ response in these cells was abolished, together with the activation of the IL-2 promoter via the transcription factor NFAT. Consequently, IL-2 production was also perturbed in these cells, compared to normal Jurkat T cells. Shb was also seen to associate with the β and γ chains of the IL-2 receptor, upon IL-2 stimulation, in T and NK cells. This association occurred between the Shb SH2 domain and Tyr-510 of the IL-2R β chain. The proline-rich domains of Shb were found to associate with the tyrosine kinases JAK1 and JAK3, which are important for STAT-mediated proliferation of T and NK cells upon IL-2 stimulation. Shb was also found to be involved in IL-2 mediated regulation of apoptosis. These findings indicate a dual role for Shb in T cells, where Shb is involved in both T cell receptor and IL-2 receptor signaling. A Shb homologue, Shf was identified, and seen to associate with the PDGF-α-receptor. Shf shares high sequence homology with Shb and a Shd (also of the Shb family) in the SH2 domain and in four motifs containing putative tyrosine phosphorylation sites. When Shf was overexpressed in fibroblasts, these cells displayed significantly lower rates of apoptosis than control cells in the presence of PDGF-AA. These findings suggest a role for the novel adapter Shf in PDGF-receptor signaling and regulation of apoptosis.

Le LAT est l'instrument principal du satellite Fermi et permet d'étudier le ciel en rayons gamma de 20 MeV à plus de 300 GeV. Sa sensibilité accrue a permis l'augmentation du nombre de sources détectées dans le domaine des hautes énergies. Une partie importante de celles-ci n'a pas de contrepartie connue et une étude multi-longueur d'onde est nécessaire afin de comprendre l'origine du signal observé. Dans un premier temps, cette thèse présente l'étude morphologique et spectrale détaillée de la source non-identifiée HESS J1745--303, qui a été découverte dans le domaine gamma par l'expérience H.E.S.S. en 2006 puis analysée spécifiquement dans un article de 2008, à l'aide des données du LAT. Deux sources ponctuelles situées à une localisation proche de HESS J1745--303 sont présentes dans le catalogue à deux ans de données de Fermi (2FGL) mais une analyse dédiée de cette région est néanmoins nécessaire vu sa complexité. Elle est en effet localisée à ~1° du Centre Galactique et à moins de 0.5° du pulsar de la Souris, les deux sources les plus brillantes en gamma dans cette région. Les différents processus d'émission de photons sont présentés dans un second temps. Leurs simulations permettent d'effectuer une étude approfondie de l'origine de l'émission détectée aux hautes et très hautes énergies par le LAT et par H.E.S.S. L'émission de cette source reste en effet encore énigmatique de nos jours et une étude multi-longueur d'onde est effectuée afin de contraindre les modèles d'émission.

No description available.

10 SUMMARY Proteins represent one of the basic building blocks of all organisms. To understand their function at the molecular level is one the critical goals of current biological, biochemical and biophysical research. It is important to characterise all aspects that affect the localisation of proteins into different compartments with specific functions, the dynamic structure of proteins and their role in multiprotein assemblies, because altering these properties can lead to various diseases. Most of the proteomic studies are nowadays performed using biochemical approaches that allow us to study multicellular organism or tissue at once. The disadvantage of these methods is complex preparation of sample and the need for a large number of cells, which leads to the loss of information at the molecular level and in individual cells. On the contrary, microscopy can provide rather detailed information about proteins of interest and at the level of a single cell. A variety of fluorescence microscopy methods in combination with recombinant DNA techniques were applied to elucidate subcellular localisation of transmembrane adaptor proteins (TRAPs) in human lymphocytes and their nanoscopic organisation at the plasma membrane. Linker of activation of T lymphocytes (LAT), phosphoprotein associated with...

This thesis takes as its starting point the use of extracts from the works of historical authors who wrote in England in the early to mid twelfth-century. It focuses upon the ways in which their works began to be incorporated into three particular texts in the later twelfth and early thirteenth centuries. Through the medium of individual case studies – De Abbatibus (Abingdon), CCCC 139 (Durham) and The London Collection three elements are explored (i) how mediaeval writers used extracts from the works of others in ways which differed from modern practices with their concerns over charges of plagiarism and unoriginality (ii) how the structural and narrative roles which the use of extracts played within the presentation of these texts (iii) how the application of approaches developed in the twentieth century, which transformed how texts are now analysed, enabled a re-evaluation and re-interpretation of their use of source material with greater sensitivity to their original purposes This analysis casts fresh light upon the how and why these texts were produced and the means by which they fulfilled their purposes and reveals that despite their disparate origins and individual perspectives these three texts share two common features: (i) they follow a common three stage pattern of development (ii) they deal with similar issues: factional insecurities and concerns about the quality of those in power over them – using an historical perspective The analysis also reveals the range of techniques which were at the disposal of the composers of these texts, dispelling any notion that they were either unsophisticated or naïve in their handling of their source materials. Together these texts demonstrate how mediaeval authors used combinations of extracts as a means of responding quickly and flexibly to address particular concerns. Such texts were not regarded as being set in stone but rather as fluid entities which could be recombined at will in order to produce new works as required.

Dédié à l'étude du ciel en rayons gamma, le satellite Fermi comporte à son bord le Large Area Telescope (LAT), sensible au rayonnement gamma de 20 MeV à 300 GeV. Les données recueillies par le LAT depuis son lancement en 2008 ont permis de multiplier par 10 le nombre de noyaux actifs de galaxie (NAG) détectés dans le domaine du GeV. Les rayons gamma observés dans les NAGs proviennent de processus énergétiques faisant intervenir des particules chargées de très haute énergie. Ces particules sont confinées dans un jet de plasma magnétisé qui prend sa source dans une région proche du trou noir supermassif habitant la zone centrale de la galaxie hôte. Ce jet s'éloigne à des vitesses aussi élevées que 0.9999c, formant dans de nombreux cas des lobes radio sur des échelles du kiloparsec voire du mégaparsec. Les NAGs dont le jet fait un angle faible avec la ligne de visée sont appelés blazars. La combinaison de cette très faible inclinaison du jet par rapport à la ligne de visée et de vitesses d'éjection relativistes donne lieu à des effets relativistes : mouvements apparents superluminiques, amplification de la luminosité et modification des échelles de temps. Les blazars sont caractérisés par une extrême variabilité à toutes les longueurs d'onde, sur des échelles de temps allant de quelques minutes à plusieurs mois. Une étude temporelle et spectrale du plus brillant d'entre ceux détectés par le LAT, 3C 454.3, a été réalisée afin de contraindre les modèles d'émission. Une nouvelle méthode de génération de courbes de lumière à échantillonnage adaptatif est également proposée dans cette thèse. Celle-ci permet d'extraire le maximum d'information des données du LAT quel que soit l'état de flux de la source.