959 resultados para Store Depletion
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inor actinides (MAs) transmutation is a main design objective of advanced nuclear systems such as generation IV Sodium Fast Reactors (SFRs). In advanced fuel cycles, MA contents in final high level waste packages are main contributors to short term heat production as well as to long-term radiotoxicity. Therefore, MA transmutation would have an impact on repository designs and would reduce the environment burden of nuclear energy. In order to predict such consequences Monte Carlo (MC) transport codes are used in reactor design tasks and they are important complements and references for routinely used deterministic computational tools. In this paper two promising Monte Carlo transport-coupled depletion codes, EVOLCODE and SERPENT, are used to examine the impact of MA burning strategies in a SFR core, 3600 MWth. The core concept proposal for MA loading in two configurations is the result of an optimization effort upon a preliminary reference design to reduce the reactivity insertion as a consequence of sodium voiding, one of the main concerns of this technology. The objective of this paper is double. Firstly, efficiencies of the two core configurations for MA transmutation are addressed and evaluated in terms of actinides mass changes and reactivity coefficients. Results are compared with those without MA loading. Secondly, a comparison of the two codes is provided. The discrepancies in the results are quantified and discussed.
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With the advent of cloud computing, many applications have embraced the ensuing paradigm shift towards modern distributed key-value data stores, like HBase, in order to benefit from the elastic scalability on offer. However, many applications still hesitate to make the leap from the traditional relational database model simply because they cannot compromise on the standard transactional guarantees of atomicity, isolation, and durability. To get the best of both worlds, one option is to integrate an independent transaction management component with a distributed key-value store. In this paper, we discuss the implications of this approach for durability. In particular, if the transaction manager provides durability (e.g., through logging), then we can relax durability constraints in the key-value store. However, if a component fails (e.g., a client or a key-value server), then we need a coordinated recovery procedure to ensure that commits are persisted correctly. In our research, we integrate an independent transaction manager with HBase. Our main contribution is a failure recovery middleware for the integrated system, which tracks the progress of each commit as it is flushed down by the client and persisted within HBase, so that we can recover reliably from failures. During recovery, commits that were interrupted by the failure are replayed from the transaction management log. Importantly, the recovery process does not interrupt transaction processing on the available servers. Using a benchmark, we evaluate the impact of component failure, and subsequent recovery, on application performance.
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UPM Activities on Sensitivity and Uncertainty Analysis of Assembly Depletion
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Propagation of nuclear data uncertainties in reactor calculations is interesting for design purposes and libraries evaluation. Previous versions of the GRS XSUSA library propagated only neutron cross section uncertainties. We have extended XSUSA uncertainty assessment capabilities by including propagation of fission yields and decay data uncertainties due to the their relevance in depletion simulations. We apply this extended methodology to the UAM6 PWR Pin-Cell Burnup Benchmark, which involves uncertainty propagation through burnup.
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En el marco del proyecto europeo FI-WARE, en el CoNWet Lab (laboratorio de la ETSI Informáticos de la UPM) se ha implementado la plataforma Web Wstore que es una implementación de referencia del Store Generic Enabler perteneciente a dicho proyecto. El objetivo de FI-WARE es crear la plataforma núcleo del Internet del Futuro (IoF) con la intención de incrementar la competitividad global europea en el mundo de las TI. El proyecto introduce una infraestructura innovadora para la creación y distribución de servicios digitales en internet. WStore ofrece a los proveedores de servicios la plataforma donde publicar sus ofertas y desde la cual los clientes podrán acceder ellas. Estos proveedores ofrecen servicios Web, aplicaciones, widgets y data sets del mismo modo que Google ofrece aplicaciones en la tienda online Google Play o Apple en el App Store. WStore está implementada actualmente como una plataforma Web, por lo que una organización que desee ofrecer el servicio de la store necesita instalar el software en un servidor propio y disponer de un dominio para ofrecer sus productos. El objetivo de este trabajo es migrar WStore a un entorno de computación en la nube de manera que con una única instancia se ofrezca el servicio a las organizaciones que deseen disponer de su propia plataforma, de la cual tendrán total control como si se encontrase en su propia infraestructura. Para esto se implementa una versión de WStore que será desplegada en una infraestructura cloud y ofrecida como Software as a Service. La implementación incluye una serie de módulos de código que se podrán añadir opcionalmente en el proceso de instalación si se desea que la instancia instalada sea Multitenant. Además, en este trabajo se estudian y prueban las herramientas que ofrece MongoDB para desplegar la plataforma Wstore Multitenant en una infraestructura cloud. Estas herramientas son replica sets y sharding que permiten desplegar una base de datos escalable y de alta disponibilidad. ---ABSTRACT---In the context of the European project FI-WARE, the CoNWeT Lab (IT Lab from ETSIINF UPM university) has been implemented the web platform WStore. WStore is a reference implementation of the Generic Enabler Store from FI-WARE project. The FI-WARE goal is to create the core platform of the Future Internet (IoF) with the intention of enhancing Europe's global competitiveness in IT technologies. FI-WARE introduces an innovative infrastructure for the creation and distribution of digital services over the Internet. WStore offers to service providers a platform to publicate offerings and where customers can access them. The providers offer web services, applications, widgets and data sets in the same way that Google offers online applications on Google Play or Apple on App Store plataforms. WStore is currently implemented as a web platform, so if an organization wants to offer the store service, it need to install the software on it’s own serves and have a domain to offer their products. The objective of this paper is to migrate WStore to a cloud computing environment where a single instance of the WStore is offered as a web service to organizations who want their own store. Customers (tenants) of the WStore web service will have total control over the software and WStore administration. The implementation includes several code modules that can be optionally added in the installation process to build a Multitenant instance. In addition, this paper review the tools that MongoDB provide for scalability and high availability (replica sets and sharding) with the purpose of deploying multi-tenant WStore on a cloud infrastructure.
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El trabajo realizado se encuentra enmarcado dentro del proyecto de I+D+I del 7o programa marco de la Comisión Europea Fi-WARE: The future Internet core platform que forma parte de la iniciativa Future Internet PPP. En concreto, se ha desarrollado la especificación de un Generic Enabler con funcionalidad de tienda virtual que de soporte a la publicación y adquisición o subscripción de aplicaciones y servicios dentro del denominado Business Framework Ecosystem (BFE), además de una implementación de referencia de este Generic Enabler (GE) que ha sido utilizada para la realización de una prueba de concepto con el objetivo de comprobar la adecuación del comportamiento de la especificación dentro del BFE. La primera tarea realizada ha consistido en un estudio de otras stores (o tiendas digitales) existentes, mirando aspectos tales como la funcionalidad proporcionada, la información mostrada de los distintos productos ofrecidos o la organización de la interfaz de usuario y la metáfora visual. Este estudio ha tenido como objetivo establecer un punto de partida desde el que empezar a analizar las distintas funcionalidades que deberá proveer el sistema.Utilizando como base el estudio anterior y las necesidades concretas de la plataforma Fi-WARE se paso a la educación de los requisitos generales del sistema en los cuales se especifica a grandes rasgos la funcionalidad que debe proveer esta tienda digital así como algunos aspectos concretos de la experiencia de usuario. Una vez definida la funcionalidad de la store se ha abordado el diseño del sistema. Para realizar este diseño se ha trabajado en dos tareas principales: La primera de estas tareas ha consistido en realizar el diseño de la arquitectura del Store GE, en el que se especifican todos los módulos que debe contener el sistema para poder satisfacer los requisitos, así como las distintas conexiones del Store GE con otros componentes del proyecto Fi-Ware y de sus interrelaciones con el resto de componentes de dicho proyecto. Esto ofrece una visión global de la ubicación del Store GE dentro de la arquitectura general del proyecto Fi-Ware. La segunda tarea ha consistido en el desarrollo de la especicación abierta (Open specication) del Store GE. Esta tarea es probablemente la más relevante de cara a cumplir con los objetivos del proyecto Fi-Ware, ya que Fi-Ware se propone como objetivo principal proporcionar las especificaciones de una plataforma tecnológica abierta para la Internet del futuro, formada por un conjunto de componentes (denominados Generic Enablers), entre los que se encuentra el Store GE. En este documento ha quedado descrito con todo detalle en que consiste el Store GE y cuales son sus APIs, sobre las que se construirán las aplicaciones de la futura Internet basadas en Fi-Ware, de manera que sea posible que cualquier empresa pueda realizar una implementación diferente a la que se está desarrollando en este proyecto (si bien ésta será su implementación de referencia). Para esta Open specication se han desarrollado un modelo de gestión de usuarios y roles, un modelo de datos, diagramas de interacción que definen todas las posibles comunicaciones de la store con otros Generic Enablers del proyecto Fi-Ware, la definición del ciclo de vida de una oferta y las APIs REST del Store GE, incluyendo el contenido de las peticiones y los tipos MIME soportados. En este punto se pudo comenzar a trabajar en la implementación de referencia del Store GE. La primera tarea ha consistido en realizar la integración con el Marketplace GE, otro de los Generic Enablers del proyecto Fi-Ware, para ello se definieron unos requisitos específicos y se realizó un diseño de bajo nivel de este móodulo seguido de la propia implementación y un conjunto exhaustivo de pruebas unitarias para comprobar su correcto funcionamiento. A continuación se pasó a realizar la integracióon con el Repository GE siguiendo los mismos pasos que con la integración con el Marketplace GE. La siguiente tarea realizada ha consistido en la realización de los móodulos necesarios para permitir crear nuevas ofertas en la implementación de referencia de Store GE incluyendo nuevamente una fase de educación de requisitos específicos, un diseño de bajo nivel, la propia implementación y una serie de pruebas unitarias. Una vez implementada la creación de nuevas ofertas, se pasó a la realización de la funcionalidad necesaria para la recuperación y visualizacion de estas ofertas así como a la realización del soporte necesario para el registro de recursos y para la vinculación de estos a determinadas ofertas, siguiendo nuevamente la metodología antes mencionada. Finalmente se ha dado el soporte para la publicación y la adquisición de ofertas. En este caso la adquisición de ofertas se ha realizado tan solo en la parte servidora de la aplicación y no se ha llegado a dar soporte a esta funcionalidad en la interfaz Web al no ser necesaria para la realización de la prueba de concepto prevista. No obstante esta funcionalidad será implementada junto con otras funcionalidades como el soporte de características sociales, ya fuera del ámbito de este Trabajo de fin de grado. Como paso previo a la realización de la prueba de concepto se ha trabajado en la plataforma Wirecloud, que es una implementación de referencia del denominado Application Mashup GE, modicando su funcionalidad para integrarla con la API de compras realizada dentro de la implementación de referencia del Store GE. La úultima tarea realizada para este Trabajo de fin de grado ha consistido por fin en la realización de la prueba de concepto del Store GE integrando su implementación de referencia con las del resto de Generic Enablers, lo cual ha permitido comprobar así el fucionamiento de la arquitectura y modelo propuestos.
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The current studies explore the mechanism by which the sphingomyelin content of mammalian cells regulates transcription of genes encoding enzymes of cholesterol synthesis. Previous studies by others have shown that depletion of sphingomyelin by treatment with neutral sphingomyelinase causes a fraction of cellular cholesterol to translocate from the plasma membrane to the endoplasmic reticulum where it expands a regulatory pool that leads to down-regulation of cholesterol synthesis and up-regulation of cholesterol esterification. Here we show that sphingomyelinase treatment of cultured Chinese hamster ovary cells prevents the nuclear entry of sterol regulatory element binding protein-2 (SREBP-2), a membrane-bound transcription factor required for transcription of several genes involved in the biosynthesis and uptake of cholesterol. Nuclear entry is blocked because sphingomyelinase treatment inhibits the proteolytic cleavage of SREBP-2 at site 1, thereby preventing release of the active NH2-terminal fragments from cell membranes. Sphingomyelinase treatment thus mimics the inhibitory effect on SREBP processing that occurs when exogenous sterols are added to cells. Sphingomyelinase treatment did not block site 1 proteolysis of SREBP-2 in 25-RA cells, a line of Chinese hamster ovary cells that is resistant to the suppressive effects of sterols, owing to an activating point mutation in the gene encoding SREBP cleavage-activating protein. In 25-RA cells, sphingomyelinase treatment also failed to down-regulate the mRNA for 3-hydroxy-3-methylglutaryl CoA synthase, a cholesterol biosynthetic enzyme whose transcription depends on the cleavage of SREBPs. Considered together with previous data, the current results indicate that cells regulate the balance between cholesterol and sphingomyelin content by regulating the proteolytic cleavage of SREBPs.
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Apoptotic and necrotic cell death are well characterized and are influenced by intracellular ATP levels. Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by DNA strand breaks, physiologically participates in DNA repair. Overactivation of PARP after cellular insults can lead to cell death caused by depletion of the enzyme’s substrate β-nicotinamide adenine dinucleotide and of ATP. In this study, we have differentially elicited apoptosis or necrosis in mouse fibroblasts. Fibroblasts from PARP-deficient (PARP−/−) mice are protected from necrotic cell death and ATP depletion but not from apoptotic death. These findings, together with cell death patterns in PARP−/− animals receiving other types of insults, indicate that PARP activation is an active trigger of necrosis, whereas other mechanisms mediate apoptosis.
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Mutation of the obese gene produces obesity, hyperinsulinemia, and compensatory “overexpression” of the defective gene. As insulin activates obese gene expression, it seemed possible that hyperinsulinemia might be responsible for overexpression of the gene. To address this question we rapidly neutralized circulating insulin by injection of an insulin antibody. Unexpectedly, insulin depletion in obese (ob/ob or db/db) mice caused massive adipose RNA degradation confirmed by histological analysis to result from adipocyte cell death by a largely necrotic mechanism. This effect was not observed in lean littermates and was completely corrected by coadministration of insulin. Comparison of multiple tissues demonstrated that the effect was restricted to adipose tissue. Insulin depletion in obese mice by administration of streptozotocin also led to cell death, but this death was less extensive and appeared to be apoptotic in mechanism. Thus insulin may promote the survival side of the physiological balance between adipocyte survival and death.
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The primary motivation behind the considerable effort in studying stratospheric ozone depletion is the potential for biological consequences of increased solar UVB (280–315 nm) radiation. Yet, direct links between ozone depletion and biological impacts have been established only for organisms of Antarctic waters under the influence of the ozone “hole;” no direct evidence exists that ozone-related variations in UVB affect ecosystems of temperate latitudes. Indeed, calculations based on laboratory studies with plants suggest that the biological impact of ozone depletion (measured by the formation of cyclobutane pyrimidine dimers in DNA) is likely to be less marked than previously thought, because UVA quanta (315–400 nm) may also cause significant damage, and UVA is unaffected by ozone depletion. Herein, we show that the temperate ecosystems of southern South America have been subjected to increasingly high levels of ozone depletion during the last decade. We found that in the spring of 1997, despite frequent cloud cover, the passages of the ozone hole over Tierra del Fuego (55° S) caused concomitant increases in solar UV and that the enhanced ground-level UV led to significant increases in DNA damage in the native plant Gunnera magellanica. The fluctuations in solar UV explained a large proportion of the variation in DNA damage (up to 68%), particularly when the solar UV was weighted for biological effectiveness according to action spectra that assume a sharp decline in quantum efficiency with increasing wavelength from the UVB into the UVA regions of the spectrum.
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The atmosphere displays modes of variability whose structures exhibit a strong longitudinally symmetric (annular) component that extends from the surface to the stratosphere in middle and high latitudes of both hemispheres. In the past 30 years, these modes have exhibited trends that seem larger than their natural background variability, and may be related to human influences on stratospheric ozone and/or atmospheric greenhouse gas concentrations. The pattern of climate trends during the past few decades is marked by rapid cooling and ozone depletion in the polar lower stratosphere of both hemispheres, coupled with an increasing strength of the wintertime westerly polar vortex and a poleward shift of the westerly wind belt at the earth's surface. Annular modes of variability are fundamentally a result of internal dynamical feedbacks within the climate system, and as such can show a large response to rather modest external forcing. The dynamics and thermodynamics of these modes are such that strong synergistic interactions between stratospheric ozone depletion and greenhouse warming are possible. These interactions may be responsible for the pronounced changes in tropospheric and stratospheric climate observed during the past few decades. If these trends continue, they could have important implications for the climate of the 21st century.
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In addition to their well-known functions in cellular energy transduction, mitochondria play an important role in modulating the amplitude and time course of intracellular Ca2+ signals. In many cells, mitochondria act as Ca2+ buffers by taking up and releasing Ca2+, but this simple buffering action by itself often cannot explain the organelle's effects on Ca2+ signaling dynamics. Here we describe the functional interaction of mitochondria with store-operated Ca2+ channels in T lymphocytes as a mechanism of mitochondrial Ca2+ signaling. In Jurkat T cells with functional mitochondria, prolonged depletion of Ca2+ stores causes sustained activation of the store-operated Ca2+ current, ICRAC (CRAC, Ca2+ release-activated Ca2+). Inhibition of mitochondrial Ca2+ uptake by compounds that dissipate the intramitochondrial potential unmasks Ca2+-dependent inactivation of ICRAC. Thus, functional mitochondria are required to maintain CRAC-channel activity, most likely by preventing local Ca2+ accumulation near sites that govern channel inactivation. In cells stimulated through the T-cell antigen receptor, acute blockade of mitochondrial Ca2+ uptake inhibits the nuclear translocation of the transcription factor NFAT in parallel with CRAC channel activity and [Ca2+]i elevation, indicating a functional link between mitochondrial regulation of ICRAC and T-cell activation. These results demonstrate a role for mitochondria in controlling Ca2+ channel activity and signal transmission from the plasma membrane to the nucleus.
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The amyloid precursor protein (APP) plays a crucial role in the pathogenesis of Alzheimer’s disease. During intracellular transport APP undergoes a series of proteolytic cleavages that lead to the release either of an amyloidogenic fragment called β-amyloid (Aβ) or of a nonamyloidogenic secreted form consisting of the ectodomain of APP (APPsec). It is Aβ that accumulates in the brain lesions that are thought to cause the disease. By reducing the cellular cholesterol level of living hippocampal neurons by 70% with lovastatin and methyl-β-cyclodextrin, we show that the formation of Aβ is completely inhibited while the generation of APPsec is unperturbed. This inhibition of Aβ formation is accompanied by increased solubility in the detergent Triton X-100 and is fully reversible by the readdition of cholesterol to previously depleted cells. Our results show that cholesterol is required for Aβ formation to occur and imply a link between cholesterol, Aβ, and Alzheimer’s disease.
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The cAMP-response element-binding protein (CREB)-binding protein and p300 are two highly conserved transcriptional coactivators and histone acetyltransferases that integrate signals from diverse signal transduction pathways in the nucleus and also link chromatin remodeling with transcription. In this report, we have examined the role of p300 in the control of the G1 phase of the cell cycle in nontransformed immortalized human breast epithelial cells (MCF10A) and fibroblasts (MSU) by using adenovirus vectors expressing p300-specific antisense sequences. Quiescent MCF10A and MSU cells expressing p300-specific antisense sequences synthesized p300 at much reduced levels and exited G1 phase without serum stimulation. These cells also showed an increase in cyclin A and cyclin A- and E-associated kinase activities characteristic of S phase induction. Further analysis of the p300-depleted quiescent MCF10A cells revealed a 5-fold induction of c-MYC and a 2-fold induction of c-JUN. A direct target of c-MYC, CAD, which is required for DNA synthesis, was also found to be up-regulated, indicating that up-regulation of c-MYC functionally contributed to DNA synthesis. Furthermore, S phase induction in p300-depleted cells was reversed when antisense c-MYC was expressed in these cells, indicating that up-regulation of c-MYC may directly contribute to S phase induction. Adenovirus E1A also induced DNA synthesis and increased the levels of c-MYC and c-JUN in serum-starved MCF10A cells in a p300-dependent manner. Our results suggest an important role of p300 in cell cycle regulation at G1 and raise the possibility that p300 may negatively regulate early response genes, including c-MYC and c-JUN, thereby preventing DNA synthesis in quiescent cells.
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Deletion of the yeast gene ACB1 encoding Acb1p, the yeast homologue of the acyl-CoA-binding protein (ACBP), resulted in a slower growing phenotype that adapted into a faster growing phenotype with a frequency >1:105. A conditional knockout strain (Y700pGAL1-ACB1) with the ACB1 gene under control of the GAL1 promoter exhibited an altered acyl-CoA profile with a threefold increase in the relative content of C18:0-CoA, without affecting total acyl-CoA level as previously reported for an adapted acb1Δ strain. Depletion of Acb1p did not affect the general phospholipid pattern, the rate of phospholipid synthesis, or the turnover of individual phospholipid classes, indicating that Acb1p is not required for general glycerolipid synthesis. In contrast, cells depleted for Acb1p showed a dramatically reduced content of C26:0 in total fatty acids and the sphingolipid synthesis was reduced by 50–70%. The reduced incorporation of [3H]myo-inositol into sphingolipids was due to a reduced incorporation into inositol-phosphoceramide and mannose-inositol-phosphoceramide only, a pattern that is characteristic for cells with aberrant endoplasmic reticulum to Golgi transport. The plasma membrane of the Acb1p-depleted strain contained increased levels of inositol-phosphoceramide and mannose-inositol-phosphoceramide and lysophospholipids. Acb1p-depleted cells accumulated 50- to 60-nm vesicles and autophagocytotic like bodies and showed strongly perturbed plasma membrane structures. The present results strongly suggest that Acb1p plays an important role in fatty acid elongation and membrane assembly and organization.