The goal of this thesis has been to reduce the hardware cost of SDF FFTs. Inorder to achieve this, two methods for simplifying rotations in FFTs are presented:Decimation and Reduction. When applied, these methods reduce the total amountof angles that the rotators need to rotate, as well as the total angle count of theFFT. This is useful for constant shift and add based rotators, as their hardwarecost are typically dependent on the amount of angles it needs to calculate.Decimation works by splitting a large twiddle factor into a smaller one plusan additional small rotator in series. This allows for the possibility to implementlarge FFTs without needing any large twiddle factors. Reduction is a method thattakes a twiddle factor and simplifies it by removing one angle from the rotator.This can be done without adding any hardware cost if applied correctly.In addition to the methods, the thesis also includes proposed designs for 64- upto 1024-point FFTs, as well as post-implementation results for a 32- and 64-pointFFT.

La sulfatation protéique est une modification post-traductionnelle qui intervient principalement sur les récepteurs cellulaires. Parmi eux, le récepteur CXCR4 est particulièrement étudié en raison de son implication dans de nombreux processus physiopathologiques (réponse immunitaire, infection au VIH). Le domaine extracellulaire de 38 acides aminés de CXCR4 (le peptide P38), contenant trois tyrosines connues pour être sulfatées, est important pour l’interaction avec son ligand spécifique, la chimiokine SDF-1α/CXCL12 (Stromal Cell-Derived Factor-1α). Le rôle de la sulfatation de CXCR4 dans cette interaction est encore méconnu.Le peptide P38 a été synthétisé et sulfaté de façon régiosélective sur toutes les tyrosines (peptides mono-, di- ou tri-sulfatés, soit 7 combinaisons). L’impact du nombre et de la position des groupements sulfate le long du peptide P38 sur son interaction avec SDF-1α a été étudié par électrophorèse capillaire d’affinité (ACE) couplée ou non à la spectrométrie de masse électrospray (ESI-MS). Une interaction entre P38 et SDF-1α a été mise en évidence par ACE. Une augmentation de l’affinité peut être associée à l’augmentation du degré de sulfatation de P38. La stœchiométrie des complexes a ensuite été déterminée en utilisant l’ACE-MS, qui a mis en évidence une majorité de complexes 1:1, quel que soit le peptide étudiéCes travaux ouvrent la voie à l'étude d'une interaction à trois partenaires avec des glycosaminoglycanes. / Sulfation is one of the most important post-translational modifications of proteins. The known sulfated proteins are mostly cell receptors and among them, CXCR4 attracts growing attention because of its involvement in numerous physio-pathological processes (immune response, HIV infection). The 38 amino-acid extracellular domain of CXCR4 (P38 peptide), containing three tyrosine residues known to be sulfated, is important for the interaction with its specific ligand, the SDF-1α/CXCL12 chemokine (Stromal cell-derived factor-1α). The role of sulfation in this interaction remains to be established.The P38 peptide was chemically synthesized and regioselectively sulfated on all the tyrosines (mono-, di- or tri-sulfated peptides, 7 combinations). The impact of both distribution and position of sulfate groups on the interaction between P38 and SDF-1α was studied by affinity capillary electrophoresis (ACE) hyphenated to electrospray mass spectrometry (ESI-MS).An interaction between P38 and SDF-1α was highlighted by ACE. It was strongly enhanced by the increase of P38 sulfation degree. The complex stoichiometry was then determined by ACE-MS, and 1:1 complexes were predominantly obtained, with all the peptides. This work opens the orad to the three-partner interaction studies involving glycosaminoglycans.

"The fundamental theorem of asset pricing in finance states that the price of any asset is its expected discounted payoff. Ideally, the payoff is discounted by a factor, which depends on parameters present in the market, and it should be unique, in the sense that financial derivatives should be able to be priced using the same discount factor. In theory, risk neutral valuation implies the existence of a positive random variable, which is called the stochastic discount factor and is used to discount the payoffs of any asset. Apart from asset pricing another use of stochastic discount factor is to evaluate the performance of the of hedge fund managers. Among many methods used to evaluate the stochastic discount factor, generalized method of moments has become very popular. In this paper we will see how generalized method of moments is used to evaluate the stochastic discount factor on linear models and the calculation of stochastic discount factor using generalized method of moments for the popular model in finance CAPM. "

Avec le développement de l'industrie électronique, on constate un nombre croissant de projets avec des contraintes matérielles et temporelles de plus en plus élevées, ce qui conduit à l'utilisation de FPGA (Field Programmable Gate Arrays). Pour cela, le concepteur doit avoir une bonne connaissance de la programmation VHDL car cela nécessite beaucoup de formation et de pratique pour maîtriser ces architectures. Mais même pour les spécialistes, le processus de développement prend beaucoup de temps. Par conséquent, le développement d'un outil pour aider les utilisateurs non experts à travailler sur FPGA est nécessaire.Des outils tels que Simulink+HDL coder proposent une interface graphique pour créer un design en posant des blocs sur un tableau et en les connectant. Malheureusement, ce type d’outil souffre de deux défauts. Le premier est qu'il ne prend pas en compte les caractéristiques physiques de l'architecture cible. L'autre est qu'il ne vérifie pas si les flux de données entrant sont traités correctement par le design. Cela oblige le développeur à créer de nombreux tests, ce qui est fastidieux et consommateur en temps. Par conséquent, ce n’est pas une solution adaptée pour produire des applications dans un environnement en temps réel et des contraintes matérielles strictes.Pour gérer la complexité et la taille croissante des designs, l’abstraction est devenue graduellement essentielle. Des modèles ont émergé afin de représenter un design comme un graphe d’acteurs (c.a.d. de blocs), avec une analyse statique de l’exécution du graphe. Néanmoins, ces modèles sont basés sur une description plus ou moins fidèle du comportement d’architecture réelles telles que les FPGAs.Dans cette thèse, nous nous concentrons sur l'étude d’un nouveau modèle et d’un nouvel outil logiciel pour aider les utilisateurs non experts à concevoir automatiquement des implémentations correctes de FPGA. Les principales contributions sont résumées comme suit:1. Les limitations des modèles SDF existants, en particulier ceux du modèle SDF-AP, sont décrites et illustrées par l'analyse d'exemples caractéristiques. Les deux problèmes les plus courants rencontrés dans les implémentations d'assemblages de blocs sont la production de résultats incorrects et la croissance infinie de la taille du tampon.2. Nous proposons un nouveau modèle appelé "Actors with Stretchable Access Patterns" (ASAP) qui décrit le comportement matériel de façon mins limitée que les approches antérieures. Il s'agit d'une manière originale de résoudre le problème d'ordonnancement des acteurs, adaptée aux FPGAs. Il permet de déterminer l'exactitude mathématique d'une exécution sans lancer de simulations complexes. Il peut non seulement modéliser correctement les comportements des acteurs, mais aussi éviter les inconvénients mentionnés ci-dessus. Des algorithmes implémentant ces principes sont également fournis.3. Nous avons étudié des stratégies et des algorithmes connexes pour analyser un graphe représentant un design. L’exactitude du traitement peut être analysée par une série d'algorithmes permettant par exemple la vérification de la vitesse des flux et la vérification de la compatibilité des patterns. Il est ainsi possible de calculer la vitesse de décimation ou la longueur de délais à appliquer sur les entrées lorsqu'une erreur de correction est détectée.4. Un logiciel d’aide à la création de design est également développé. Il est appelé BlAsT (Block Assembly Tool) et vise à compenser les inconvénients des outils similaires tels que Simulink + HDL. Dans BlAsT, les algorithmes du modèle ASAP sont utilisés pour vérifier que pour un flux d'entrée donné, le système peut produire un résultat correct et finalement générer des codes VHDL directement utilisables sur une carte FPGA réelle. De plus, l'outil détermine automatiquement les décimations et les modifications requises. Ainsi, un utilisateur sans aucune compétence de programmation, est capable créer un design pour FPGA. / With the development of electronic industry, a growing number of projects require real-time streaming applications on embedded platforms. These comprise increasingly high hardware and timing constraints, which leads to the use of FPGAs (Field Programmable Gate Arrays). Usually, the designer should have a good knowledge of programming with VHDL or Verilog HDL. Unfortunately, only specialists can do it, because this needs a lot of training and practices to master these architectures. Furthermore, even for specialists, the process of development is quite time consuming. Therefore, how to develop a tool to help non-expert users working on FPGA is a promising but challenging work.Tools like Simulink+HDL coder provide a graphical interface to create a design, by putting functional blocks on a layer and to connect them. Nevertheless, such tools are generally suffering from two flaws. One is that they do not take the physical characteristics of the target architecture of the application into account, including that of the selected FPGA. The other one is that they do not check whether a data stream is processed correctly by the design, besides creating many test-benches, which is tedious and time consuming for the developer. Therefore, they are not suitable to produce applications in real-time environment and high hardware constraints.In order to manage the ever-increasing size and complexity of designs, the abstraction is gradually more and more essential. Some models have emerged to represent a design as a graph of actors (i.e. blocks), with a static analysis of the graph execution. Nevertheless, they have an unfaithful description of the behavior real architectures like an FPGA.In this dissertation, we concentrate on the study of a novel model and software tool that can help non-expert users for automatic design of FPGA implementations correctly. The main contributions are summarized as follows:1. The limits of existing SDF models, in particular those of the SDF-AP model, are described and illustrated by the analysis of characteristic examples. The two most common problems encountered in block assembly implementations are the production of incorrect results and the infinite growth of buffer size.2. We propose a new model called Actors Stretchable Access Patterns (ASAP) that describes the hardware behaviors as efficiently and precisely as possible. This is a novel way to address the scheduling problem of actors, adapted to FPGA architectures. It opens the possibility to determine the execution correctness mathematically without launching complex simulations. It can not only model actors' behaviors properly, but also avoid the above mentioned drawbacks. Algorithms that implement these principles also provided.3. We investigate strategies and related algorithms to analyze a graph representing a designed system. Its correctness can be analyzed by a series of algorithms, such as sample rate checking and pattern compatibility checking. The decimation rate or the delay length to be applied on actor's input can be computed when a correctness failure is detected. This increases the number of possible real FPGA implementations covered by the block assembly method.4. A software tool based on the concept of functional block graph is also developed. It is called BlAsT (Block Assembly Tool) and aims to compensate the drawbacks of other tools based on the same concepts, as for example Simulink + HDL coder. In BlAsT, the proposed ASAP model and related algorithms are used to check that for a given input stream, whether the system can produce a correct result and finally generate VHDL code directly usable on a real FPGA-based board. Otherwise, the tool determines the required decimations and modifications on the graph automatically. It makes a user without any programming skills to make designs on FPGAs thanks to the friendly graphic interface.

No description available.

Multiple myeloma (MM) is an incurable haematological malignancy characterised by the clonal proliferation of plasma cells (PCs) within the bone marrow (BM). MM PC survival and expansion is dependent upon an adequate supply of oxygen and nutrients, and increased BM angiogenesis is a critical feature of MM progression. While MM PCs express and secrete a number of angiogenic factors, our current understanding of the precise mechanisms by which MM-induced angiogenesis occurs is incomplete. In this study, we collected specimens from patients with MM and the benign precursor condition MGUS, and demonstrated for the first time that circulating levels of the CXCL12 chemokine positively correlate with the degree of BM angiogenesis. Using conditioned media from a MM PC line, the contribution of MM PC-derived CXCL12 to angiogenesis was also examined and found to strongly induce vascular tube formation in vitro. In several other cell types, hypoxia has been shown to up-regulate CXCL12 expression. Studies investigating the hypoxic regulation of CXCL12 in MM PCs revealed that, while acute hypoxia is unable to stimulate CXCL12 expression, prolonged hypoxia significantly up-regulates CXCL12 mRNA and protein expression. To determine the mechanism(s) responsible for this, over-expression and RNA interference technology was employed to create genetically modified MM cells in which either HIF-1α or HIF-2α were overexpressed or knocked down. These studies showed that HIF-2α is the predominant mediator of the hypoxic induction of CXCL12 in MM PCs. The ability of HIF-2α to bind to the CXCL12 promoter was confirmed using EMSA and ChIP analyses. The role of CXCL12 in in vivo angiogenesis and the contribution of HIF-1α and HIF-2α were also examined. In these studies, transduced MM cells, in which HIF-1α, HIF-2α and CXCL12 were over-expressed or knocked down, were implanted into a vessel-poor, subcutaneous environment in immunocompromised mice. Tumour-induced angiogenesis was assessed after two weeks by measuring the haemoglobin content of excised implants. These studies confirmed that over-expression of CXCL12, HIF-1α and HIF-2α each stimulates a strong angiogenic response. Using the well-characterised CXCR4 antagonist, T140, CXCL12 was found to play a key role in the increased angiogenesis observed in response to HIF-1α and HIF-2α over-expression. These novel studies have shown that CXCL12 is an important mediator of angiogenesis in MM patients, and that aberrant CXCL12 expression by MM PCs is due, in part, to its hypoxic up-regulation mediated predominantly by HIF-2. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1365126 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009

Multiple myeloma (MM) is an incurable haematological malignancy characterised by the clonal proliferation of plasma cells (PCs) within the bone marrow (BM). MM PC survival and expansion is dependent upon an adequate supply of oxygen and nutrients, and increased BM angiogenesis is a critical feature of MM progression. While MM PCs express and secrete a number of angiogenic factors, our current understanding of the precise mechanisms by which MM-induced angiogenesis occurs is incomplete. In this study, we collected specimens from patients with MM and the benign precursor condition MGUS, and demonstrated for the first time that circulating levels of the CXCL12 chemokine positively correlate with the degree of BM angiogenesis. Using conditioned media from a MM PC line, the contribution of MM PC-derived CXCL12 to angiogenesis was also examined and found to strongly induce vascular tube formation in vitro. In several other cell types, hypoxia has been shown to up-regulate CXCL12 expression. Studies investigating the hypoxic regulation of CXCL12 in MM PCs revealed that, while acute hypoxia is unable to stimulate CXCL12 expression, prolonged hypoxia significantly up-regulates CXCL12 mRNA and protein expression. To determine the mechanism(s) responsible for this, over-expression and RNA interference technology was employed to create genetically modified MM cells in which either HIF-1α or HIF-2α were overexpressed or knocked down. These studies showed that HIF-2α is the predominant mediator of the hypoxic induction of CXCL12 in MM PCs. The ability of HIF-2α to bind to the CXCL12 promoter was confirmed using EMSA and ChIP analyses. The role of CXCL12 in in vivo angiogenesis and the contribution of HIF-1α and HIF-2α were also examined. In these studies, transduced MM cells, in which HIF-1α, HIF-2α and CXCL12 were over-expressed or knocked down, were implanted into a vessel-poor, subcutaneous environment in immunocompromised mice. Tumour-induced angiogenesis was assessed after two weeks by measuring the haemoglobin content of excised implants. These studies confirmed that over-expression of CXCL12, HIF-1α and HIF-2α each stimulates a strong angiogenic response. Using the well-characterised CXCR4 antagonist, T140, CXCL12 was found to play a key role in the increased angiogenesis observed in response to HIF-1α and HIF-2α over-expression. These novel studies have shown that CXCL12 is an important mediator of angiogenesis in MM patients, and that aberrant CXCL12 expression by MM PCs is due, in part, to its hypoxic up-regulation mediated predominantly by HIF-2. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1365126 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009

Multiple myeloma (MM) is an incurable haematological malignancy characterised by the clonal proliferation of plasma cells (PCs) within the bone marrow (BM). MM PC survival and expansion is dependent upon an adequate supply of oxygen and nutrients, and increased BM angiogenesis is a critical feature of MM progression. While MM PCs express and secrete a number of angiogenic factors, our current understanding of the precise mechanisms by which MM-induced angiogenesis occurs is incomplete. In this study, we collected specimens from patients with MM and the benign precursor condition MGUS, and demonstrated for the first time that circulating levels of the CXCL12 chemokine positively correlate with the degree of BM angiogenesis. Using conditioned media from a MM PC line, the contribution of MM PC-derived CXCL12 to angiogenesis was also examined and found to strongly induce vascular tube formation in vitro. In several other cell types, hypoxia has been shown to up-regulate CXCL12 expression. Studies investigating the hypoxic regulation of CXCL12 in MM PCs revealed that, while acute hypoxia is unable to stimulate CXCL12 expression, prolonged hypoxia significantly up-regulates CXCL12 mRNA and protein expression. To determine the mechanism(s) responsible for this, over-expression and RNA interference technology was employed to create genetically modified MM cells in which either HIF-1α or HIF-2α were overexpressed or knocked down. These studies showed that HIF-2α is the predominant mediator of the hypoxic induction of CXCL12 in MM PCs. The ability of HIF-2α to bind to the CXCL12 promoter was confirmed using EMSA and ChIP analyses. The role of CXCL12 in in vivo angiogenesis and the contribution of HIF-1α and HIF-2α were also examined. In these studies, transduced MM cells, in which HIF-1α, HIF-2α and CXCL12 were over-expressed or knocked down, were implanted into a vessel-poor, subcutaneous environment in immunocompromised mice. Tumour-induced angiogenesis was assessed after two weeks by measuring the haemoglobin content of excised implants. These studies confirmed that over-expression of CXCL12, HIF-1α and HIF-2α each stimulates a strong angiogenic response. Using the well-characterised CXCR4 antagonist, T140, CXCL12 was found to play a key role in the increased angiogenesis observed in response to HIF-1α and HIF-2α over-expression. These novel studies have shown that CXCL12 is an important mediator of angiogenesis in MM patients, and that aberrant CXCL12 expression by MM PCs is due, in part, to its hypoxic up-regulation mediated predominantly by HIF-2. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1365126 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009

No description available.

Schwannzellen sind die myelinisierenden Zellen des peripheren Nervensystems, die auch eine Rolle bei Entzündungs- und Regenerationsprozessen spielen. Diese Arbeit beschäftigt sich mit der Bedeutung der Chemokinrezeptoren CXCR4 und CXCR7 bei der SDF-1-abhängigen Signalübermittlung in der Schwannzelllinie RN22. Mittels PCR, Western-Blotting und FACS erfolgte zunächst ein Expressionsnachweis der Chemokinrezeptoren. Anschließend wurde mittels Western-Blotting festgestellt, dass eine Behandlung mit SDF-1 zu einer Aktivierung der intrazellulären Signalkinasen Erk1/2, p38 und Akt führt. Für PKC ζ/λ wurde kein Effekt beobachtet. Durch Einsatz der spezifischen Antagonisten für CXCR4 (AMD3100) und CXCR7 (CCX733) konnten diese Effekte blockiert werden. Die Ergebnisse legen nahe, dass beide Rezeptoren ihren Liganden binden müssen, damit ein intrazellulärer Effekt auftritt. Ähnliches gilt auch für die SDF-1-abhängige Migration von RN22-Zellen, die ebenfalls bereits durch einen der beiden Antagonisten unterbunden werden kann.