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Caractérisation de l’interaction entre la phosphatidylinositol 5-phosphatase SHIP2 et la protéine adaptatrice APS et étude du rôle de ce complexe protéique dans la régulation de la cascade de signalisation de l’insuline.Onnockx, Sheela 31 January 2008 (has links)
La liaison de l’insuline à son récepteur permet le recrutement de protéines adaptatrices, ce qui conduit notamment à l’activation de la voie mitogénique des MAPK et des voies impliquées dans le métabolisme du glucose. Deux voies complémentaires contribuent au recrutement du transporteur de glucose, GLUT4, à la membrane ; la voie de la PI3-kinase qui implique la formation du messager secondaire PtdIns(3,4,5)P3 conduisant à l’activation de la PKB et la voie de la petite protéine G, TC10, qui implique les protéines APS, CAP et c-Cbl.
La phosphatidylinositol 5-phosphatase 2 (SHIP2) contrôle négativement la voie des MAPK par interaction avec des acteurs de la cascade et la voie de la PI3-kinase en hydrolysant le PtIns(3,4,5)P3 en PtIns(3,4)P2. De plus, il a été montré dans notre laboratoire que SHIP2 peut interagir directement avec la protéine CAP ainsi que co-immunoprécipiter avec le récepteur de l’insuline et c-Cbl, participant ainsi à un complexe multiprotéique formé des protéines CAP et c-Cbl et du récepteur. Au cours de ce travail, nous avons tenté de mieux comprendre l’implication moléculaire de SHIP2 dans la cascade TC10. Comme APS est la première protéine de la cascade à être recrutée au récepteur suite à une stimulation par l’insuline et qu’elle peut interagir directement avec le récepteur et les protéines CAP et c-Cbl, nous avons étudié dans un premier temps le lien potentiel entre APS et SHIP2.
Nous avons montré que SHIP2 interagit de manière directe avec la protéine adaptatrice APS tant dans un système de sur-expression (CHO-IR) que dans un système endogène (3T3-L1). Bien qu’une stimulation par l’insuline ne semble pas modifier cette interaction, elle induit néanmoins le recrutement d’une fraction des protéines APS et SHIP2 du cytoplasme vers la membrane plasmique. L’étude des domaines d’interaction a montré que la région centrale de SHIP2 qui comprend le domaine catalytique est nécessaire pour cette association.
Nous avons ensuite montré que cette association entre APS et SHIP2 peut moduler certaines de leurs propriétés biochimiques. D’une part, bien que la sur-expression de SHIP2 n’influence pas le recrutement d’APS au récepteur, SHIP2 diminue, indépendamment de son activité enzymatique, la phosphorylation sur tyrosine d’APS induite par l’insuline et l’interaction entre APS et c-Cbl, qui sont deux étapes cruciales dans la cascade TC10. Ainsi, SHIP2 pourrait non seulement influencer la cascade de l’insuline par son activité enzymatique, mais également par interaction avec des acteurs de la cascade. D’autre part, APS augmente l’activité 5-phosphatase de SHIP2 dans un test in vitro. Elle pourrait ainsi, outre son rôle positif dans la cascade, participer au rétrocontrôle négatif de la voie de signalisation à l’insuline. Finalement, nous avons déterminé comment ces deux protéines influencent les cascades de l’insuline. Alors qu’APS n’influence pas l’activation de la PKB, ni le taux de PtdIns(3,4,5)P3, la sur-expression d’APS et de SHIP2 induit une inhibition plus forte de l’activation de la PKB comparée à celle provoquée par SHIP2 seul. De plus, une sur-expression de SHIP2 abolit l’augmentation induite par APS de la phosphorylation des MAPK. Cette activation des MAPK par APS semble dépendre de sa liaison au récepteur car les domaines PH et essentiellement SH2 sont indispensables pour cet effet positif.
En conclusion, nous avons mis en évidence l’existence d’une association entre APS et SHIP2. Cette interaction modifie certaines de leurs propriétés biochimiques et fournit un nouveau mécanisme d’action pour ces protéines dans le contrôle négatif de la voie de signalisation à l’insuline.
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Case studies in Advanced Planning Systems for Tactical Planning in Process IndustriesCederborg, Ola January 2010 (has links)
This thesis focuses on the use of Advanced Planning System (APSs) in the tactical planning process. In addition, there is a special focus towards process industries. The overall aim is to find out if and how APSs can support the tactical planning processes and add value to the company. A discussion on APSs as such is also presented, as the general definition of APS is unclear. The study is based on three case studies, first a longitudinal case study at a single company, second a in-depth case study at the same company and last a multiple case study at four Scandinavian companies. The case descriptions provide answers to the overall purpose of the thesis, but they also contribute to the general knowledge concerning APSs, as they describe industrial use of these systems. The study reveals several improvements that companies have achieved by implementing APSs and it conclude that APSs can support the tactical planning process. The improvements are seen either as results of process changes needed to implement the APS or the APS itself. Among the improvements, centralizing, automatizing and streamlining of the tactical planning processes are three of the most prominent. But several other improvements are also found, for example improvements concerning the customer service level and inventory levels. Although several successful implementations, it is not uncommon that implementations projects fail, which is why companies need to be careful when deciding to invest in an APS. Factors found to be linked to success concerning APS implementations are discussed, with the APS’s fit to the company’s processes and existing systems along with promotional activities, either by a project champion or the top management, are found to be important. / ISCAPS / PIC-LI
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The Adoption and Adaptation of Supply Chain Management Systems for High Tech. IndustriesChiang, Kuang-Chih 28 July 2000 (has links)
Abstract:
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Posibilidades y Limitaciones del manejo Transferencial en Pacientes con Diagnóstico de Trastorno de Personalidad en el contexto de la Atención Primaria de SaludBusta Cornejo, Cristián 08 1900 (has links)
Magíster
en Psicología Clínica de Adultos / El presente trabajo busca desarrollar una investigación en torno a las posibilidades técnicas del psicoanálisis en relación al manejo de la transferencia en el diagnostico de Trastorno de Personalidad en el contexto de Atención Primaria de Salud. A partir de la contextualización del trabajo clínico con pacientes diagnosticados con Trastorno de Personalidad en Atención Primaria de Salud, se buscará realizar una lectura desde el psicoanálisis de casos diagnosticados con dicho diagnostico en el contexto de APS, a fin de poder discutir, describir e ilustrar aspectos específicos de la experiencia de trabajo con este tipo de casos. De esta manera, se busca poder caracterizar y describir a estos pacientes, a partir de una lectura que considere elementos teóricos propios de la orientación psicoanalítica y con ello, de las posibilidades y limitaciones técnicas del manejo de la transferencia, en el contexto de un consultorio de atención primaria de salud.
Mediante lo recientemente expuesto, se busca generar conocimiento en torno a las posibilidades técnicas que el psicoanálisis puede ofrecer en el contexto de la salud pública, a partir de un diagnóstico que ofrece diversas dificultades para la intervención terapéutica de los profesionales de salud mental que se desempeñan en dicho contexto, dificultades que serán discutidas a lo largo del presente trabajo.
Se propone una metodología empírica de tipo cualitativo, basada en la entrevista a un grupo de psicólogos que trabajan desde una orientación psicoanalítica, que a su vez hayan trabajado con pacientes diagnosticados con trastorno de personalidad, ya sea en contextos públicos o privados, a fin de poder pesquisar las dificultades, limitaciones y posibilidades con que se han enfrentado dichos profesionales en su quehacer clínico para con estos pacientes, y con ello poder generar aportes en el contexto de la APS en torno al quehacer clínico a partir de la información recabada. Se plantea una lectura de la problemática clínica propuesta desde categorías conceptuales propuestas por la orientación psicoanalítica en torno a la dirección de la cura, específicamente en torno a los desarrollos propuestos por Freud y Lacan
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Incidentes em reatores nucleares de pesquisa examinados por análise de probabilidade determinística e análise probabilística de segurança / Incidents in nuclear research reactor examined by deterministic probability and probabilistic safety analysisLopes, Valdir Maciel 21 October 2010 (has links)
O presente trabalho tem o objetivo de avaliar os riscos potenciais apresentados pelos incidentes em reatores nucleares de pesquisa. Para o desenvolvimento do trabalho, duas bases de dados do Organismo Internacional de Energia Atômica, OIEA, foram usadas, o Incident Report System for Research Reactor e Research Reactor Data Base. Para este tipo de avaliação fez-se uso de Análise Probabilística de Segurança (APS), dentro de um limite de confiança de 90% e, Análise de Probabilidades determinística (APD). Para obtenção dos resultados dos cálculos de probabilidades por APS, utilizou-se a teoria e as equações sugeridas em documento da IAEA TECDOC - 636. O desenvolvimento dos cálculos das probabilidades por APS utilizou-se o Programa Scilab versão 5.1.1, de livre acesso, executável nas plataformas do Windows, Linux. Um programa específico para obter os resultados das probabilidades foi desenvolvido dentro do programa principal Scilab 5.1.1., para duas distribuições Fischer e Chi-quadrado, ambas no limite de confiança de 90%. Fazendo uso das equações de Sordi e do programa Origin 6.0, foram obtidas as doses máximas admissíveis relacionadas às probabilidades que satisfazem os limites de riscos estabelecidos pela Comissão Internacional de Proteção Radiológica, CIPR e, pode-se também obter estas doses máximas graficamente com a figura 1 resultante dos cálculos de probabilidades x doses máximas admissíveis. Verificou-se que a confiabilidade nos resultados das probabilidades está relacionada com a experiência operacional (reator x ano e fração) e, que quanto maior ela for, maior é a confiabilidade no resultado. Finalizando, sugere-se uma lista de futuros trabalhos que complementam este. / This study aims to evaluate the potential risks submitted by the incidents in nuclear research reactors. For its development, two databases of the International Atomic Energy Agency, IAEA, were used, the Incident Report System for Research Reactor and Research Reactor Data Base. For this type of assessment was used the Probabilistic Safety Analysis (PSA), within a confidence level of 90% and the Deterministic Probability Analysis (DPA). To obtain the results of calculations of probabilities for PSA, were used the theory and equations in the paper IAEA TECDOC - 636. The development of the calculations of probabilities for PSA was used the program Scilab version 5.1.1, free access, executable on Windows and Linux platforms. A specific program to get the results of probability was developed within the main program Scilab 5.1.1., for two distributions Fischer and Chi-square, both with the confidence level of 90%. Using the Sordi equations and Origin 6.0 program, were obtained the maximum admissible doses related to satisfy the risk limits established by the International Commission on Radiological Protection, ICRP, and were also obtained these maximum doses graphically figure1 resulting from the calculations of probabilities x maximum admissible doses. It was found that the reliability of the results of probability is related to the operational experience (reactor x year and fractions) and that the larger it is, greater the confidence in the outcome. Finally, a suggested list of future work to complement this paper was gathered.
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Incidentes em reatores nucleares de pesquisa examinados por análise de probabilidade determinística e análise probabilística de segurança / Incidents in nuclear research reactor examined by deterministic probability and probabilistic safety analysisValdir Maciel Lopes 21 October 2010 (has links)
O presente trabalho tem o objetivo de avaliar os riscos potenciais apresentados pelos incidentes em reatores nucleares de pesquisa. Para o desenvolvimento do trabalho, duas bases de dados do Organismo Internacional de Energia Atômica, OIEA, foram usadas, o Incident Report System for Research Reactor e Research Reactor Data Base. Para este tipo de avaliação fez-se uso de Análise Probabilística de Segurança (APS), dentro de um limite de confiança de 90% e, Análise de Probabilidades determinística (APD). Para obtenção dos resultados dos cálculos de probabilidades por APS, utilizou-se a teoria e as equações sugeridas em documento da IAEA TECDOC - 636. O desenvolvimento dos cálculos das probabilidades por APS utilizou-se o Programa Scilab versão 5.1.1, de livre acesso, executável nas plataformas do Windows, Linux. Um programa específico para obter os resultados das probabilidades foi desenvolvido dentro do programa principal Scilab 5.1.1., para duas distribuições Fischer e Chi-quadrado, ambas no limite de confiança de 90%. Fazendo uso das equações de Sordi e do programa Origin 6.0, foram obtidas as doses máximas admissíveis relacionadas às probabilidades que satisfazem os limites de riscos estabelecidos pela Comissão Internacional de Proteção Radiológica, CIPR e, pode-se também obter estas doses máximas graficamente com a figura 1 resultante dos cálculos de probabilidades x doses máximas admissíveis. Verificou-se que a confiabilidade nos resultados das probabilidades está relacionada com a experiência operacional (reator x ano e fração) e, que quanto maior ela for, maior é a confiabilidade no resultado. Finalizando, sugere-se uma lista de futuros trabalhos que complementam este. / This study aims to evaluate the potential risks submitted by the incidents in nuclear research reactors. For its development, two databases of the International Atomic Energy Agency, IAEA, were used, the Incident Report System for Research Reactor and Research Reactor Data Base. For this type of assessment was used the Probabilistic Safety Analysis (PSA), within a confidence level of 90% and the Deterministic Probability Analysis (DPA). To obtain the results of calculations of probabilities for PSA, were used the theory and equations in the paper IAEA TECDOC - 636. The development of the calculations of probabilities for PSA was used the program Scilab version 5.1.1, free access, executable on Windows and Linux platforms. A specific program to get the results of probability was developed within the main program Scilab 5.1.1., for two distributions Fischer and Chi-square, both with the confidence level of 90%. Using the Sordi equations and Origin 6.0 program, were obtained the maximum admissible doses related to satisfy the risk limits established by the International Commission on Radiological Protection, ICRP, and were also obtained these maximum doses graphically figure1 resulting from the calculations of probabilities x maximum admissible doses. It was found that the reliability of the results of probability is related to the operational experience (reactor x year and fractions) and that the larger it is, greater the confidence in the outcome. Finally, a suggested list of future work to complement this paper was gathered.
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Molecular properties of human monoclonal anti-DNA and antiphospholipid antibodiesRahman, Mohammed Abbas Anisur January 1998 (has links)
No description available.
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Antiendothelial cell antibodies : associations and functional implicationsGraham, Audrey January 2001 (has links)
No description available.
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Thermal barrier coatings for diesel engine exhaust applications / Termiska barriärsskikt för grenrörsapplikationerBlomqvist, Christoffer January 2014 (has links)
The strive to increase the engine efficiency in terms of fuel consumption and lower emissions have lead to higher demands on materials. In this thesis five different thermal barrier coatings applied using air plasma spraying to three materials commonly used for exhaust application are evaluated. This thesis work was done at Scania CV in Södertälje with main focus on evaluation during thermal cycling. The goal of this thesis is to evaluate the coatings and correlate their behaviour to their characteristic microstructure. The coatings were evaluated through their stability in thermal conductivity, fracture toughness, hardness, porosity and failure modes. The parameters where obtained using laser flash, Vickers indentation, Vickers indentation fracture toughness and microscopic evaluation methods. The evaluation shows that conventionally used zirconia based materials exhibits low thermal conductivity, high hardness, and stable fracture toughness compared to other evaluated materials. One material that can be applicable in diesel exhaust application is mullite, which showed similar performance to zirconia based materials. For the use of TBC together with SiMo51 a different bondcoat than conventional NiCrAlY needs to be evaluated. / Strävan efter att konstruera effektivare motorer för att generera minskade utsläpp och bättre bränsleekonomi har genererat högre krav på konstruktionsmaterialen som används idag. I detta examensarbete som utförts på Scania CV i Södertälje utvärderas fem olika termiska barriärsskikt som belagts med plasma sprayning på tre vanligt förekommande konstruktionsmaterial för grenrör. Målet med detta examensarbete är att utvärdera beläggningarnas beteende under termisk cykling och koppla deras beteende till karakteristiska mikrostrukturer. Beläggningarna utvärderades genom att jämföra deras värmeledningsförmåga, hårdhet, brottseghet och porositet. Materialparametrarna utvärderades genom laser flash, Vickers hårdhetsmätning, Vickers brottseghet samt mikroskopiska bildanalyser. Resultaten visar att kommersiellt använda zirkonium baserade material uppvisar låg värmeledningsförmåga, hög hårdhet och hög brottseghet i förhållande till övriga material. Ett annat material som analyserats, mullit, visar på liknande beteenden som zirkonium baserade material men behöver utvärderas ytterligare. Om SiMo51 används som substratmaterial finns behovet att utvärdera användningen av andra typer av bindskikt än det austenitiska NiCrAlY nu använt.
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The Paragenesis and Chemical Variation of Alteration Minerals Associated with Basement Rocks of the P2 Fault and the McArthur River Uranium Deposit, Athabasca Basin, Northern Saskatchewan, Canada.Adlakha, Erin Elizabeth January 2016 (has links)
The P2 reverse fault in the metasedimentary basement rocks of the eastern Athabasca Basin is the main structural control of the world-class McArthur River uranium deposit. The earliest preserved assemblage along the fault is oxy-dravite, rutile, quartz, pyrite and graphite. This assemblage formed at temperatures of up to 890 °C, during regional metamorphism or a thermal event at ~1.75 Ga. The exhumation and surface exposure of the rocks was accompanied by paleo-weathering, and the deposition of the Athabasca sandstones. Diagenetic fluids of the sandstones altered the basement rocks to form Sr-Ca-SO42- rich aluminum phosphate sulfate (APS) minerals + hematite ± kaolin. The onset of hydrothermal activity along the basement and the P2 fault is recorded by local anatase at 1569 ± 31 Ma. Uraniferous fluid formed an assemblage of sudoite illite, magnesio-foitite and LREE+P rich APS minerals (rims earlier diagenetic-type APS minerals) along the entire P2 fault. Magnesio-foitite exhibits a high X-site vacancy (0.70 – 0.85 apfu) and contains high Al in its Y-site (0.70 – 1.12 apfu), suggesting that magnesio-foitite likely replaced kaolin. The REE pattern of magnesio-foitite is similar to that of uraninite (CeN<YN), likely due to their co-crystallization with LREE-rich APS minerals. APS minerals show variably high S/P ratios (0.05 - 0.21) in proximity to the deposit and low ratios (0.11 - 0.13) far from the deposit along the P2 fault, indicating reducing conditions in the ore zone. Low values of δD (-41 to -98 ‰) and high values of δ11B (+13.1 to +23.2 ‰) for magnesio-foitite suggest that groundwater interacted with carbonates or evaporites and was progressively enriched in 11B through interaction with illite and kaolin minerals.
This work demonstrates that i) the P2 fault was a site of extensive fluid-rock interaction, ii) mineralizing fluids travelled along the entire P2 fault in the basement, iii) the deposition of the McArthur River deposit was controlled by the availability of a reducing fluid through the P2 fault, and iv) mineral chemistry (tourmaline and APS minerals) may help identify fertile faults in exploration for uranium deposits.
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