Global ETD Search

71	A review of the impact of Canadian law, policy and P3 practice on the case for procuring capital-intensive infrastructure services via P3s Jatto, Lucky Bryce Jr 02 September 2011 (has links) This dissertation investigates the advantages of procuring capital-intensive infrastructure services via Public-Private Partnerships (P3s or PPPs) – cost and time savings and; innovation and high levels of efficiency – accounting for these advantages by reference to the underlying legal provisions and principles that facilitate them; and in this process highlights two significant directions in which Canadian P3 law, policy and practice has evolved – the enactment of P3 legislation and/or the formulation of non-statutory P3-related policy; as well as the establishment of legal institutions that promote and/or facilitate P3 procurements. The dissertation also addresses key arguments raised against P3s, by reference to aspects of Canadian law, policy and P3 practice. The research methodology comprises a detailed review of legal and non-legal sources. The implication of the research findings is that, given the foregoing developments in Canadian P3 law, policy and practice, the key arguments canvassed against P3s are overstated and lacking in merit. P3s PPPs P3 PPP PFI AFP PFIs AFPs infrastructure procurement investment private public public-private private-public policy law units conventional contract legislation statute case partnerships BOT BOO BOOT DBFM DBFO Operate finance project BF DBM DBOM partnership DBFOM concession concessions JVA JVAs O&M/M O&M BBO DB BT VfM risk penalties public-private partnerships
72	Etude des effets de l'inactivation des isoformes B et C de l'enzyme INS(1,4,5)Pp3s 3-kinase chez la souris ;Rôle de l'INS(1,4,5)Pp3s3-kinase B dans le développement des lymphocytes T Pouillon, Valérie 28 January 2004 (has links) L’Ins(1,4,5)P3 joue un rôle évident dans la signalisation cellulaire :il permet la libération du Ca 2+ des stocks intracellulaires par son action au niveau de récepteurs spécifiques. Pour mettre fin à son action, l’Ins(1,4,5)P3 peut être dégradé par une Ins(1,4,5)P3 5-phosphatase en Ins(1,4)P2, un métabolite inactif. L’Ins(1,4,5)P3 peut aussi être transformé en Ins(1,3,4,5)P4 par une Ins(1,4,5)P3 3-kinase. L’Ins(1,3,4,5)P4 semble posséder des capacités de signalisation propres ou au contraire liées à celles de l’Ins(1,4,5)P3.<p>L’Ins(1,3,4,5)P4 est aussi le point de départ de toute une série d’inositol hautement phosphorylés, dont les rôles ne sont pas clairs. Trois isoformes de l’Ins(1,4,5)P3 3-kinase existent (A, B et C). Ces isoformes possèdent un domaine catalytique carboxy-terminal bien conservé. Par contre, les domaines amino-terminaux sont spécifiques et leur permettraient d’établir des interactions ou de subir des régulations propres. Pour tenter d’élucider le rôle fonctionnel de l’Ins(1,3,4,5)P4, nous avons généré et analysé des souris déficientes pour les isoformes B et C de cette enzyme.<p>Les souris déficientes pour l’Ins(1,4,5)P3 3-kinase C ne présentent pas de phénotype évident, ce qui suggère que son rôle n’est pas crucial ou que son absence peut être compensée par une autre enzyme.<p>Les souris déficientes pour l’Ins(1,4,5)P3 3-kinase B, par contre, présentent une immunodéficience caractérisée par une absence spécifique des lymphocytes T αβ périphériques. Cette absence fait suite à un blocage dans la différenciation du précurseur du lymphocyte, le thymocyte. Les caractéristiques de la signalisation induite par le récepteur de surface (TCR) permettent la sélection des thymocytes, de manière à constituer un pool de lymphocytes T restreints pour le MHC et tolérants pour le soi. Nous avons montré que ces phénomènes de sélection étaient défectueux dans les thymocytes mutants, du fait de leur hyporéactivité à la stimulation par le TCR. Le mécanisme responsable de cette hyporéactivité n’est pas encore élucidé. A première vue, la mobilisation de Ca 2+ ne semble pas altérée dans ces thymocytes mutants en réponse à des stimulations classiques. Cependant, d’autres types de stimulation, se rapprochant plus de celles réellement rencontrées par le thymocyte in vivo, doivent encore être investigués. L’intégrité d’autres voies de signalisation cruciales du lymphocyte T doit aussi être vérifiée.<p>En conclusion, l’isoforme B de l’Ins(1,4,5)P3 3-kinase et l’Ins(1,3,4,5)P4 qu’il produit jouent un rôle crucial dans la différenciation du thymocyte, par un mécanisme qui reste encore à déterminer. / Doctorat en sciences biomédicales / info:eu-repo/semantics/nonPublished Médecine pathologie humaine Disciplines biomédicales diverses T cells Immunodeficiency Autoimmunity Inositol phosphates Lymphocytes T Immunodéficience Auto-immunité Inositol phosphates immunodéficience thymocyte sélection immunologie inositol phosphate Ins(1 3 4 5)P4 knock out Ins(1 4 5)P3 3-kinase autoimmunité
73	TELEMETRY IN THEATER MISSILE DEFENSE DEVELOPMENT Toole, Michael T. 10 1900 (has links) International Telemetering Conference Proceedings / October 17-20, 1994 / Town & Country Hotel and Conference Center, San Diego, California / Since the Gulf War, there has been significant interest in Theater Missile Defense (TMD) resulting in funding growth from tens of millions of dollars at the time of the Gulf War to $1.7 Billion in 1994. The Ballistic Missile Defense Organization (BMDO) has developed a Theater Missile Defense test and evaluation program that will assess technological feasibility and the degree to which system functionality and performance meet technical and operational requirements. The complexity of the TMD program necessitates a comprehensive test program which includes flight testing, ground testing, and modeling and simulation. This article will provide and overview the requirements and capabilities needed to satisfy these requirements. The data processing, and telemetry communities will play a major role in providing the expertise to support the development of the nation’s future Theater Missile Defense capabilities. Theater Missile Defense test and evaluation system performance live flight testing ground testing modeling and simulation Air Defense CINCs experiments optical measurement X-band measurement phenomenology data collection THAAD interceptor radar BMC3 System Integration Test ERINT missile Sealite Beam Director High Energy Laser National Test Facility Airborne Surveillance Testbed HALO Rapid Optical Beam Sensing system Cobra Eye Cobra Judy Aria P3 GPS WSMR TSPI Kwajalein distributed interactive simulation
74	A dissection of class I phosphoinositide 3-kinase signalling in mouse embryonic fibroblasts and prostate organoids Sadiq, Barzan A. January 2018 (has links) Class I PI3Ks are a family (α, β, δ and γ) of ubiquitous lipid kinases that can be activated by cell surface receptors to 3-phosphorylate PI(4,5)P2 (phosphatidylinositol(4,5)-bisphosphate) and generate the signalling lipid PI(3,4,5)P3. The PI(3,4,5)P3 signal then activates a diverse collection of effector proteins involved in regulation of cell migration, metabolism and growth. The importance of this network is evidenced by the relatively high frequency with which cancers acquire gain-of-function mutations in this pathway and huge efforts to make PI3K inhibitors to treat cancer. The canonical model describing these events suggests class I PI3Ks are activated at the plasma membrane and generate PI(3,4,5)P3 in the inner leaflet of the plasma membrane where its effectors are activated. The PI(3,4,5)P3 signal can be terminated directly, by the tumour-suppressor and PI(3,4,5)P3-3-phosphatase PTEN, or modified to a distinct PI(3,4)P2 signal, by SHIP-family 5-phosphatases. The PI(3,4)P2 is removed by INPP4-family 4-phosphatases. Published work has shown that PI(3,4,5)P3 signalling can also occur in endosomes and nuclei, however, there is very little data defining the intracellular distribution of endogenous class I PI3Ks that supports these ideas; this is as a result of technical problems such as; their very low abundance, poor antibody-based tools and artefacts generated by overexpression of PI3Ks. Past work has indicated that, in PTEN-null mouse models of prostate tumour progression, either PI3Kβ or PI3Ks α and β, have important roles. Furthermore, the cell types and mechanism involved remained unclear. Recent published work in the host laboratory had indicated that there is an unexpectedly large accumulation of PI(3,4)P2 in PTEN-null cells that might be an important part of its status as a major tumour suppressor. The explanation and prevalence of this observation was unclear but potentially a result of PTEN also acting as a PI(3,4)P2 3-phosphatase in vivo. MEFs were derived from genetically-modified mice expressing endogenous, AviTagged class I PI3K subunits and used in experiments to define the subcellular localisation of class I PI3Ks. We found that following stimulation with PDGF, class IA PI3K subunits were unexpectedly depleted from the adherent basal membrane, in contrast, p85α and p110α, but not p85β and p110β, accumulated transiently in the nucleus. Interestingly, p110β, but none of the other subunits, was constitutively localised in the nucleus. These results support the idea that class I PI3K and PI(3,4,5)P3 signalling occurs in the nucleus. In organoids derived from WT, PI3Kγ-null or PTEN-null mouse prostate, application of PI3K-selective inhibitors revealed that PI3Kα had a dominant role in generating PI(3,4,5)P3 in prostate epithelial cells. The levels of PI(3,4)P2 were also elevated substantially in PTEN-null, compared to WT prostate organoids, use of PI3K-selective inhibitors suggested that it was also generated by PI3Kα. These data were consistent with the idea that PTEN can act as a PI(3,4)P2 3-phosphatase. Surprisingly, raising the pH of the organoids medium dramatically increased accumulation of PI(3,4,5)P3 and PI(3,4)P2, although the cause of this effect was unclear, we hypothesised the pH of the local environment may influence signalling via class I PI3Ks.

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