947 resultados para business cycles, investment cycles, spectral tests
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After construction of the LYSS (Light cYcling Stressing Source) in early 2014, several CPV receivers, with and without secondary optical element (SOE) have been aged under fast transient illumination cycling,. The test plan for Madrid consisted of 50000 cycles. Receivers with poor heat spreaders showed low reliability but those with thicker metal layers passed the test well. The operation of LYSS along 8 months, after more than 250000 cycles, did not show any significant failure, except lamp reposition every 120 hours, in average. The equipment seems valid for unveiling weak receiver designs with respect to intensive illumination, in steady and transient modes.
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Los sistemas transaccionales tales como los programas informáticos para la planificación de recursos empresariales (ERP software) se han implementado ampliamente mientras que los sistemas analíticos para la gestión de la cadena de suministro (SCM software) no han tenido el éxito deseado por la industria de tecnología de información (TI). Aunque se documentan beneficios importantes derivados de las implantaciones de SCM software, las empresas industriales son reacias a invertir en este tipo de sistemas. Por una parte esto es debido a la falta de métodos que son capaces de detectar los beneficios por emplear esos sistemas, y por otra parte porque el coste asociado no está identificado, detallado y cuantificado suficientemente. Los esquemas de coordinación basados únicamente en sistemas ERP son alternativas válidas en la práctica industrial siempre que la relación coste-beneficio esta favorable. Por lo tanto, la evaluación de formas organizativas teniendo en cuenta explícitamente el coste debido a procesos administrativos, en particular por ciclos iterativos, es de gran interés para la toma de decisiones en el ámbito de inversiones en TI. Con el fin de cerrar la brecha, el propósito de esta investigación es proporcionar métodos de evaluación que permitan la comparación de diferentes formas de organización y niveles de soporte por sistemas informáticos. La tesis proporciona una amplia introducción, analizando los retos a los que se enfrenta la industria. Concluye con las necesidades de la industria de SCM software: unas herramientas que facilitan la evaluación integral de diferentes propuestas de organización. A continuación, la terminología clave se detalla centrándose en la teoría de la organización, las peculiaridades de inversión en TI y la tipología de software de gestión de la cadena de suministro. La revisión de la literatura clasifica las contribuciones recientes sobre la gestión de la cadena de suministro, tratando ambos conceptos, el diseño de la organización y su soporte por las TI. La clasificación incluye criterios relacionados con la metodología de la investigación y su contenido. Los estudios empíricos en el ámbito de la administración de empresas se centran en tipologías de redes industriales. Nuevos algoritmos de planificación y esquemas de coordinación innovadoras se desarrollan principalmente en el campo de la investigación de operaciones con el fin de proponer nuevas funciones de software. Artículos procedentes del área de la gestión de la producción se centran en el análisis de coste y beneficio de las implantaciones de sistemas. La revisión de la literatura revela que el éxito de las TI para la coordinación de redes industriales depende en gran medida de características de tres dimensiones: la configuración de la red industrial, los esquemas de coordinación y las funcionalidades del software. La literatura disponible está enfocada sobre todo en los beneficios de las implantaciones de SCM software. Sin embargo, la coordinación de la cadena de suministro, basándose en el sistema ERP, sigue siendo la práctica industrial generalizada, pero el coste de coordinación asociado no ha sido abordado por los investigadores. Los fundamentos de diseño organizativo eficiente se explican en detalle en la medida necesaria para la comprensión de la síntesis de las diferentes formas de organización. Se han generado varios esquemas de coordinación variando los siguientes parámetros de diseño: la estructura organizativa, los mecanismos de coordinación y el soporte por TI. Las diferentes propuestas de organización desarrolladas son evaluadas por un método heurístico y otro basado en la simulación por eventos discretos. Para ambos métodos, se tienen en cuenta los principios de la teoría de la organización. La falta de rendimiento empresarial se debe a las dependencias entre actividades que no se gestionan adecuadamente. Dentro del método heurístico, se clasifican las dependencias y se mide su intensidad basándose en factores contextuales. A continuación, se valora la idoneidad de cada elemento de diseño organizativo para cada dependencia específica. Por último, cada forma de organización se evalúa basándose en la contribución de los elementos de diseño tanto al beneficio como al coste. El beneficio de coordinación se refiere a la mejora en el rendimiento logístico - este concepto es el objeto central en la mayoría de modelos de evaluación de la gestión de la cadena de suministro. Por el contrario, el coste de coordinación que se debe incurrir para lograr beneficios no se suele considerar en detalle. Procesos iterativos son costosos si se ejecutan manualmente. Este es el caso cuando SCM software no está implementada y el sistema ERP es el único instrumento de coordinación disponible. El modelo heurístico proporciona un procedimiento simplificado para la clasificación sistemática de las dependencias, la cuantificación de los factores de influencia y la identificación de configuraciones que indican el uso de formas organizativas y de soporte de TI más o menos complejas. La simulación de eventos discretos se aplica en el segundo modelo de evaluación utilizando el paquete de software ‘Plant Simulation’. Con respecto al rendimiento logístico, por un lado se mide el coste de fabricación, de inventario y de transporte y las penalizaciones por pérdida de ventas. Por otro lado, se cuantifica explícitamente el coste de la coordinación teniendo en cuenta los ciclos de coordinación iterativos. El método se aplica a una configuración de cadena de suministro ejemplar considerando diversos parámetros. Los resultados de la simulación confirman que, en la mayoría de los casos, el beneficio aumenta cuando se intensifica la coordinación. Sin embargo, en ciertas situaciones en las que se aplican ciclos de planificación manuales e iterativos el coste de coordinación adicional no siempre conduce a mejor rendimiento logístico. Estos resultados inesperados no se pueden atribuir a ningún parámetro particular. La investigación confirma la gran importancia de nuevas dimensiones hasta ahora ignoradas en la evaluación de propuestas organizativas y herramientas de TI. A través del método heurístico se puede comparar de forma rápida, pero sólo aproximada, la eficiencia de diferentes formas de organización. Por el contrario, el método de simulación es más complejo pero da resultados más detallados, teniendo en cuenta parámetros específicos del contexto del caso concreto y del diseño organizativo. ABSTRACT Transactional systems such as Enterprise Resource Planning (ERP) systems have been implemented widely while analytical software like Supply Chain Management (SCM) add-ons are adopted less by manufacturing companies. Although significant benefits are reported stemming from SCM software implementations, companies are reluctant to invest in such systems. On the one hand this is due to the lack of methods that are able to detect benefits from the use of SCM software and on the other hand associated costs are not identified, detailed and quantified sufficiently. Coordination schemes based only on ERP systems are valid alternatives in industrial practice because significant investment in IT can be avoided. Therefore, the evaluation of these coordination procedures, in particular the cost due to iterations, is of high managerial interest and corresponding methods are comprehensive tools for strategic IT decision making. The purpose of this research is to provide evaluation methods that allow the comparison of different organizational forms and software support levels. The research begins with a comprehensive introduction dealing with the business environment that industrial networks are facing and concludes highlighting the challenges for the supply chain software industry. Afterwards, the central terminology is addressed, focusing on organization theory, IT investment peculiarities and supply chain management software typology. The literature review classifies recent supply chain management research referring to organizational design and its software support. The classification encompasses criteria related to research methodology and content. Empirical studies from management science focus on network types and organizational fit. Novel planning algorithms and innovative coordination schemes are developed mostly in the field of operations research in order to propose new software features. Operations and production management researchers realize cost-benefit analysis of IT software implementations. The literature review reveals that the success of software solutions for network coordination depends strongly on the fit of three dimensions: network configuration, coordination scheme and software functionality. Reviewed literature is mostly centered on the benefits of SCM software implementations. However, ERP system based supply chain coordination is still widespread industrial practice but the associated coordination cost has not been addressed by researchers. Fundamentals of efficient organizational design are explained in detail as far as required for the understanding of the synthesis of different organizational forms. Several coordination schemes have been shaped through the variation of the following design parameters: organizational structuring, coordination mechanisms and software support. The different organizational proposals are evaluated using a heuristic approach and a simulation-based method. For both cases, the principles of organization theory are respected. A lack of performance is due to dependencies between activities which are not managed properly. Therefore, within the heuristic method, dependencies are classified and their intensity is measured based on contextual factors. Afterwards the suitability of each organizational design element for the management of a specific dependency is determined. Finally, each organizational form is evaluated based on the contribution of the sum of design elements to coordination benefit and to coordination cost. Coordination benefit refers to improvement in logistic performance – this is the core concept of most supply chain evaluation models. Unfortunately, coordination cost which must be incurred to achieve benefits is usually not considered in detail. Iterative processes are costly when manually executed. This is the case when SCM software is not implemented and the ERP system is the only available coordination instrument. The heuristic model provides a simplified procedure for the classification of dependencies, quantification of influence factors and systematic search for adequate organizational forms and IT support. Discrete event simulation is applied in the second evaluation model using the software package ‘Plant Simulation’. On the one hand logistic performance is measured by manufacturing, inventory and transportation cost and penalties for lost sales. On the other hand coordination cost is explicitly considered taking into account iterative coordination cycles. The method is applied to an exemplary supply chain configuration considering various parameter settings. The simulation results confirm that, in most cases, benefit increases when coordination is intensified. However, in some situations when manual, iterative planning cycles are applied, additional coordination cost does not always lead to improved logistic performance. These unexpected results cannot be attributed to any particular parameter. The research confirms the great importance of up to now disregarded dimensions when evaluating SCM concepts and IT tools. The heuristic method provides a quick, but only approximate comparison of coordination efficiency for different organizational forms. In contrast, the more complex simulation method delivers detailed results taking into consideration specific parameter settings of network context and organizational design.
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A novel type I transmembrane protein of COPI-coated vesicles, p23, has been demonstrated to be localized mainly to the Golgi complex. This protein and p24, another member of the p24 family, have been shown to bind coatomer via their short cytoplasmic tails. Here we demonstrate that p23 continuously cycles through the early secretory pathway. The cytoplasmic tail of p23 is shown to act as a functional retrieval signal as it confers endoplasmic reticulum (ER) residence to a CD8–p23 fusion protein. This ER localization is, at least in part, a result of retrieval from post-ER compartments because CD8–p23 fusion proteins receive post-ER modifications. In contrast, the cytoplasmic tail of p24 has been shown not to retrieve a CD8–p24 fusion protein. The coatomer binding motifs FF and KK in the cytoplasmic tail of p23 are reported to influence the steady-state localization of the CD8–p23 fusion protein within the ER–Golgi recycling pathway. It appears that the steady-state Golgi localization of endogenous p23 is maintained by its lumenal domain, as a fusion protein with the lumenal domain of CD8, and the membrane span as well as the cytoplasmic tail of p23 is no longer detected in the Golgi.
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Kinesin is a processive motor protein: A single molecule can walk continuously along a microtubule for several micrometers, taking hundreds of 8-nm steps without dissociating. To elucidate the biochemical and structural basis for processivity, we have engineered a heterodimeric one-headed kinesin and compared its biochemical properties to those of the wild-type two-headed molecule. Our construct retains the functionally important neck and tail domains and supports motility in high-density microtubule gliding assays, though it fails to move at the single-molecule level. We find that the ATPase rate of one-headed kinesin is 3–6 s−1 and that detachment from the microtubule occurs at a similar rate (3 s−1). This establishes that one-headed kinesin usually detaches once per ATP hydrolysis cycle. Furthermore, we identify the rate-limiting step in the one-headed hydrolysis cycle as detachment from the microtubule in the ADP⋅Pi state. Because the ATPase and detachment rates are roughly an order of magnitude lower than the corresponding rates for two-headed kinesin, the detachment of one head in the homodimer (in the ADP⋅Pi state) must be accelerated by the other head. We hypothesize that this results from internal strain generated when the second head binds. This idea accords with a hand-over-hand model for processivity in which the release of the trailing head is contingent on the binding of the forward head. These new results, together with previously published ones, allow us to propose a pathway that defines the chemical and mechanical cycle for two-headed kinesin.
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The MAL proteolipid is a nonglycosylated integral membrane protein found in glycolipid-enriched membrane microdomains. In polarized epithelial Madin-Darby canine kidney cells, MAL is necessary for normal apical transport and accurate sorting of the influenza virus hemagglutinin. MAL is thus part of the integral machinery for glycolipid-enriched membrane–mediated apical transport. At steady state, MAL is predominantly located in perinuclear vesicles that probably arise from the trans-Golgi network (TGN). To act on membrane traffic and to prevent their accumulation in the target compartment, integral membrane elements of the protein-sorting machinery should be itinerant proteins that cycle between the donor and target compartments. To establish whether MAL is an itinerant protein, we engineered the last extracellular loop of MAL by insertion of sequences containing the FLAG epitope or with sequences containing residues that became O-glycosylated within the cells or that displayed biotinylatable groups. The ectopic expression of these modified MAL proteins allowed us to investigate the surface expression of MAL and its movement through different compartments after internalization with the use of a combination of assays, including surface biotinylation, surface binding of anti-FLAG antibodies, neuraminidase sensitivity, and drug treatments. Immunofluorescence and flow cytometric analyses indicated that, in addition to its Golgi localization, MAL was also expressed on the cell surface, from which it was rapidly internalized. This retrieval implies transport through the endosomal pathway and requires endosomal acidification, because it can be inhibited by drugs such as chloroquine, monensin, and NH4Cl. Resialylation experiments of surface MAL treated with neuraminidase indicated that ∼30% of the internalized MAL molecules were delivered to the TGN, probably to start a new cycle of cargo transport. Together, these observations suggest that, as predicted for integral membrane members of the late protein transport machinery, MAL is an itinerant protein cycling between the TGN and the plasma membrane.
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The hair follicle cycle successively goes through the anagen, catagen, telogen, and latency phases, which correspond, respectively, to hair growth, arrest, shedding, and absence before a new anagen phase is initiated. Experimental observations collected over a period of 14 years in a group of 10 male volunteers, alopecic and nonalopecic, allowed us to determine the characteristics of scalp hair follicle cycles. On the basis of these observations, we propose a follicular automaton model to simulate the dynamics of human hair cycles. The automaton model is defined by a set of rules that govern the stochastic transitions of each follicle between the successive states anagen, telogen, and latency, and the subsequent return to anagen. The transitions occur independently for each follicle, after time intervals given stochastically by a distribution characterized by a mean and a variance. The follicular automaton model accounts both for the dynamical transitions observed in a single follicle and for the behavior of an ensemble of independently cycling follicles. Thus, the model successfully reproduces the evolution of the fractions of follicle populations in each of the three phases, which fluctuate around steady-state or slowly drifting values. We apply the follicular automaton model to the study of spatial patterns of follicular growth that result from a spatially heterogeneous distribution of parameters such as the mean duration of anagen phase. When considering that follicles die or miniaturize after going through a critical number of successive cycles, the model can reproduce the evolution to hair patterns similar to well known types of diffuse or androgenetic alopecia.
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Recent advances in biologically based ecosystem models of the coupled terrestrial, hydrological, carbon, and nutrient cycles have provided new perspectives on the terrestrial biosphere’s behavior globally, over a range of time scales. We used the terrestrial ecosystem model Century to examine relationships between carbon, nitrogen, and water dynamics. The model, run to a quasi-steady-state, shows strong correlations between carbon, water, and nitrogen fluxes that lead to equilibration of water/energy and nitrogen limitation of net primary productivity. This occurs because as the water flux increases, the potentials for carbon uptake (photosynthesis), and inputs and losses of nitrogen, all increase. As the flux of carbon increases, the amount of nitrogen that can be captured into organic matter and then recycled also increases. Because most plant-available nitrogen is derived from internal recycling, this latter process is critical to sustaining high productivity in environments where water and energy are plentiful. At steady-state, water/energy and nitrogen limitation “equilibrate,” but because the water, carbon, and nitrogen cycles have different response times, inclusion of nitrogen cycling into ecosystem models adds behavior at longer time scales than in purely biophysical models. The tight correlations among nitrogen fluxes with evapotranspiration implies that either climate change or changes to nitrogen inputs (from fertilization or air pollution) will have large and long-lived effects on both productivity and nitrogen losses through hydrological and trace gas pathways. Comprehensive analyses of the role of ecosystems in the carbon cycle must consider mechanisms that arise from the interaction of the hydrological, carbon, and nutrient cycles in ecosystems.
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We explain a technical result about p-adic cohomology and apply it to the study of Shimura varieties. The technical result applies to algebraic varieties with torsion-free cohomology, but for simplicity we only treat abelian varieties.
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Three-week-old maize (Zea mays L.) plants were submitted to light/dark cycles and to prolonged darkness to investigate the occurrence of sugar-limitation effects in different parts of the whole plant. Soluble sugars fluctuated with light/dark cycles and dropped sharply during extended darkness. Significant decreases in protein level were observed after prolonged darkness in mature roots, root tips, and young leaves. Glutamine and asparagine (Asn) changed in opposite ways, with Asn increasing in the dark. After prolonged darkness the increase in Asn accounted for most of the nitrogen released by protein breakdown. Using polyclonal antibodies against a vacuolar root protease previously described (F. James, R. Brouquisse, C. Suire, A. Pradet, P. Raymond [1996] Biochem J 320: 283–292) or the 20S proteasome, we showed that the increase in proteolytic activities was related to an enrichment of roots in the vacuolar protease, with no change in the amount of 20S proteasome in either roots or leaves. Our results show that no significant net proteolysis is induced in any part of the plant during normal light/dark cycles, although changes in metabolism and growth appear soon after the beginning of the dark period, and starvation-related proteolysis probably appears in prolonged darkness earlier in sink than in mature tissues.
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The GroE proteins are molecular chaperones involved in protein folding. The general mechanism by which they facilitate folding is still enigmatic. One of the central open questions is the conformation of the GroEL-bound nonnative protein. Several suggestions have been made concerning the folding stage at which a protein can interact with GroEL. Furthermore, the possibility exists that binding of the nonnative protein to GroEL results in its unfolding. We have addressed these issues that are basic for understanding the GroE-mediated folding cycle by using folding intermediates of an Fab antibody fragment as molecular probes to define the binding properties of GroEL. We show that, in addition to binding to an early folding intermediate, GroEL is able to recognize and interact with a late quaternary-structured folding intermediate (Dc) without measurably unfolding it. Thus, the prerequisite for binding is not a certain folding stage of a nonnative protein. In contrast, general surface properties of nonnative proteins seem to be crucial for binding. Furthermore, unfolding of a highly structured intermediate does not necessarily occur upon binding to GroEL. Folding of Dc in the presence of GroEL and ATP involves cycles of binding and release. Because in this system no off-pathway reactions or kinetic traps are involved, a quantitative analysis of the reactivation kinetics observed is possible. Our results indicate that the association reaction of Dc and GroEL in the presence of ATP is rather slow, whereas in the absence of ATP association is several orders of magnitude more efficient. Therefore, it seems that ATP functions by inhibiting reassociation rather than promoting release of the bound substrate.
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This testimony discusses proposed legislation to amend the definition of accredited investor. It also discusses proposed legislation designed to reform the regulatory framework for business development companies. Among other things, the regulatory regime for BDCs would change to allow these companies to invest a greater portion of their assets in financial companies, potentially reducing the percentage of assets invested in operating companies.