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Last Several Years (last + several_year)
Selected AbstractsManaging very large distributed data sets on a data gridCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 11 2010Miguel Branco Abstract In this work we address the management of very large data sets, which need to be stored and processed across many computing sites. The motivation for our work is the ATLAS experiment for the Large Hadron Collider (LHC), where the authors have been involved in the development of the data management middleware. This middleware, called DQ2, has been used for the last several years by the ATLAS experiment for shipping petabytes of data to research centres and universities worldwide. We describe our experience in developing and deploying DQ2 on the Worldwide LHC computing Grid, a production Grid infrastructure formed of hundreds of computing sites. From this operational experience, we have identified an important degree of uncertainty that underlies the behaviour of large Grid infrastructures. This uncertainty is subjected to a detailed analysis, leading us to present novel modelling and simulation techniques for Data Grids. In addition, we discuss what we perceive as practical limits to the development of data distribution algorithms for Data Grids given the underlying infrastructure uncertainty, and propose future research directions. Copyright © 2009 John Wiley & Sons, Ltd. [source] ,-synuclein has a dynamic intracellular localizationCYTOSKELETON, Issue 8 2006Irina Surgucheva Abstract ,-Synuclein is a member of the synuclein family consisting of three proteins. Within the last several years increasing attention has focused on these proteins because of their role in human diseases. ,-Synuclein relevance to Parkinson's disease is based on mutations found in familial cases of the disease and its presence in filaments and inclusion bodies in sporadic cases. ,-Synuclein is implicated in some forms of cancer and ocular diseases, while ,-synuclein may antagonize their pathological functions. In this paper we present data on the localization and properties of ,-synuclein in several neuronal and nonneuronal cell cultures. We show that contrary to the current opinion, ,-synuclein is not an exclusively cytoplasmic protein, but has a dynamic localization and can associate with subcellular structures. It is present in the perinuclear area and may be associated to centrosomes. On late steps of mitosis ,-synuclein is not found in the centrosomes, and redistributes to the midbody in telophase. Under stress conditions a translocation of ,-synuclein from the perinuclear area to the nucleus occurs exhibiting nucleocytoplasmic shuttling. ,-Synuclein overexpression reduces neurite outgrowth in a greater extent then ,-synuclein overexpression. These data support the view that ,-synuclein may change its intracellular localization and associate with subcellular structures in response to intracellular signaling or stress. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source] Recent progress in enantiomeric separation by capillary electrochromatographyELECTROPHORESIS, Issue 22-23 2002Jingwu Kang Abstract Recent progress in enantiomeric separations by capillary electrochromatography (CEC) is reviewed. The development of simple and robust CEC column technologies plays an important role for popularization of CEC. During the last several years, various approaches for the preparation of enantioselective columns have been reported. Currently, the monolithic column technology (continuous beds) represents the most advanced approach for the preparation of CEC columns. The development of new chiral stationary phase used for CEC is another important issue in this field. Fundamental investigations on electrochromatographic behaviors of various CSPs are necessary in order to understand the separation mechanism and thus improve the separation performance. Some chiral stationary phases performed better under nonaqueous CEC conditions than reversed-phase conditions. Coupling CEC with mass spectrometry (MS) provides a powerful tool for enantiomeric separation. Finally, some applications of enantiomeric separation by CEC are summarized. [source] Interstrand crosslink inducing agents in pretransplant conditioning therapy for hematologic malignanciesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2010Benigno C. Valdez Abstract Despite successful molecularly targeted, highly specific, therapies for hematologic malignancies, the DNA interstrand crosslinking agents, which are among the oldest and least specific cytotoxic drugs, still have an important role. This is particularly true in stem cell transplantation, where virtually every patient receives conditioning therapy with a DNA-alkylating agent-based program. However, due to concern about serious additive toxicities with combinations of different alkylating drugs, the last several years have seen nucleoside analogs, whose cytotoxic action follows vastly different molecular pathways, introduced in combination with alkylating agents. The mechanistic differences paired with different metabolic pathways for the respective drugs have clinically translated into increased safety without appreciable loss of antileukemic activity. In this report, we review pre-clinical evidence for synergistic antileukemic activity when nucleoside analog(s) and DNA-alkylating agent(s) are combined in the most appropriate manner(s), without a measurable decrease in clinical efficacy compared with the more established alkylating agent combinations. Data from our own laboratory using combinations of fludarabine, clofarabine, and busulfan as prototype representatives for these respective classes of cytotoxic agents are combined with information from other investigators to explain how the observed molecular events will result in greatly enhanced synergistic cytotoxicity. We further present possible mechanistic pathways for such desirable cytotoxic synergism. Finally, we propose how this information-backed hypothesis can be incorporated in the design of the next generation conditioning therapy programs in stem cell transplantation to optimize antileukemic efficacy while still safeguarding patient safety. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc. [source] A Paradigm Shift in Hydrology: Storage Thresholds Across Scales Influence Catchment Runoff GenerationGEOGRAPHY COMPASS (ELECTRONIC), Issue 7 2010Christopher Spence A paradigm shift is occurring in the science surrounding runoff generation processes. Results of recent field investigations in landscapes and during periods previously unobservable are shaping new ideas on how runoff is generated and transferred from the hillslope to the catchment outlet. The previous paradigm saw runoff generation and contributing area variability as a continuum. The new paradigm is based not on continual storage satisfaction and runoff generation but threshold-mediated, connectivity-controlled processes dictated by heterogeneity in the catchment. This review focuses on the body of literature summarizing research on storage, storage thresholds and runoff generation, particularly over the last several years during which this paradigm shift has occurred. Storage thresholds that control the release of water exist at scales as small as the soil matrix and as large as the catchment. Hysteresis in storage,runoff relationships at all scales manifest because of these thresholds. Because storage thresholds at a range of scales have now been recognized as important, connectivity has become an important concept crucial to understanding how water is transferred through a catchment. This new paradigm requires basins to be instrumented within the context of a water budget investigation, with measurements taken within key catchment units, in order to be successful. New model approaches that incorporate connectivity are required to address the findings of field hydrologists. These steps are crucial if our community wishes to adopt the holisitic view of the catchment necessary to answer the questions posed to us by the society. [source] CARMA1-mediated NF-,B and JNK activation in lymphocytesIMMUNOLOGICAL REVIEWS, Issue 1 2009Marzenna Blonska Summary:, Activation of transcription factor nuclear factor-,B (NF-,B) and Jun N-terminal kinase (JNK) play the pivotal roles in regulation of lymphocyte activation and proliferation. Deregulation of these signaling pathways leads to inappropriate immune response and contributes to the development of leukemia/lymphoma. The scaffold protein CARMA1 [caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1] has a central role in regulation of NF-,B and the JNK2/c-Jun complex in both B and T lymphocytes. During last several years, tremendous work has been done to reveal the mechanism by which CARMA1 and its signaling partners, B cell CLL-lymphoma 10 and mucosa-associated lymphoid tissue 1, are activated and mediate NF-,B and JNK activation. In this review, we summarize our findings in revealing the roles of CARMA1 in the NF-,B and JNK signaling pathways in the context of recent advances in this field. [source] On robust control algorithms for nonlinear network consensus protocolsINTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 3 2010Qing Hui Abstract Even though many consensus protocol algorithms have been developed over the last several years in the literature, robustness properties of these algorithms involving nonlinear dynamics have been largely ignored. Robustness here refers to sensitivity of the control algorithm achieving semistability and consensus in the face of model uncertainty. In this paper, we examine the robustness of several control algorithms for network consensus protocols with information model uncertainty of a specified structure. In particular, we develop sufficient conditions for robust stability of control protocol functions involving higher-order perturbation terms that scale in a consistent fashion with respect to a scaling operation on an underlying space with the additional property that the protocol functions can be written as a sum of functions, each homogeneous with respect to a fixed scaling operation, that retain system semistability and consensus. Copyright © 2009 John Wiley & Sons, Ltd. [source] Global Government Health Partners' Forum 2006: eighteen months laterINTERNATIONAL NURSING REVIEW, Issue 2 2010J. Foster rn FOSTER J., GUISINGER V., GRAHAM A., HUTCHCRAFT L. & SALMON M. (2010) Global Government Health Partners' Forum 2006: eighteen months later. International Nursing Review57, 173,179 Background:, The challenge of global health worker shortages, particularly among nurses, has been the topic of numerous forums over the last several years. Nevertheless, there has been little attention given to the roles of government chief nursing and medical officers as key partners in addressing health worker shortages. This partnership and its potential impact on the adequacy of the global health workforce was the focus of the most recent Global Government Health Partners (GGHP) Forum held in November 2006 in Atlanta, Georgia, USA. This forum was uniquely designed to create a context for government chief nursing officers and chief medical officers to engage in a joint learning and planning experience focused on positioning their leadership to impact health workforce issues. Aim:, This article describes an 18-month follow-up evaluation of the outcomes of the GGHP. The purpose of the evaluation was to assess the impact of the forum experience on the actions of participants based on the country-level plans they produced at the forum. This important feedback is intended to inform the design of future partnered global forums and gain insights into the utility of forum-based action plans. The evaluation process itself has served as an opportunity for the engagement of university faculty, students and staff in a global service learning experience. Conclusion:, The outcomes of this evaluation indicate that important progress has been made by countries whose leadership was involved in the forum, and was also an important learning activity for those participating in the conduct of the study. [source] Axon or dendrite? cell biology and molecular pathways for neuronal cell asymmetryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2008Masashi Kishi Abstract Young neurons polarize by specializing axons and dendrites from immature neurites. After synapse formations, they transmit electrical activity along the axon-dendrite axis, thereby working as functional units of the neural circuits. This axon-dendrite asymmetry is referred to as neuronal polarity. Although a great number of cell biological studies in vitro had been performed, little was known about the molecular events that establish the polarity. In the last several years, rapid advancement in molecular and genetic studies has unraveled the multiple signaling pathways. This paper summarizes current perspectives on the cell and molecular biological mechanisms of the neuronal polarization, to clarify future directions in this growing research field. © 2007 Wiley-Liss, Inc. [source] Antibody structure, instability, and formulationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2007Wei Wang Abstract The number of therapeutic monoclonal antibody in development has increased tremendously over the last several years and this trend continues. At present there are more than 23 approved antibodies on the US market and an estimated 200 or more are in development. Although antibodies share certain structural similarities, development of commercially viable antibody pharmaceuticals has not been straightforward because of their unique and somewhat unpredictable solution behavior. This article reviews the structure and function of antibodies and the mechanisms of physical and chemical instabilities. Various aspects of formulation development have been examined to identify the critical attributes for the stabilization of antibodies. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1,26, 2007 [source] Recent Advances in linear and nonlinear Raman spectroscopy IJOURNAL OF RAMAN SPECTROSCOPY, Issue 12 2007W. Kiefer Abstract Raman spectroscopy has advanced considerably in the last several years due to rapid developments in instrumentation and the availability of theoretical methods for accurate calculation of Raman spectra, thus enormously facilitating the interpretation of Raman data. This review is restricted to cover papers mainly published in the Journal of Raman Spectroscopy, which serve to give a fast overview of recent advances in this research field as well as to provide readers of this journal a quick introduction to the various subfields of Raman spectroscopy. It also reflects the current research interests of the Raman community. Similar reviews of highly active areas of Raman spectroscopy will appear in future issues of this journal. Copyright © 2007 John Wiley & Sons, Ltd. [source] Laminins and their roles in mammalsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 5 2008Jeffrey H. Miner Abstract Laminins are ,-,-, heterotrimeric components of all basement membranes. Laminins are now known to play the central role in organizing and establishing the basement membrane. The diversity of laminins allows them to impart special structural and signaling properties to the basement membrane. Of the 12 known laminin chain genes, 10 have been either found to be mutated in humans or experimentally mutated in mice. This has led to great progress over the last several years towards understanding both the functions of laminins and the reasons for their great diversity. In this review, I will summarize the in vivo studies in mice and humans that have contributed to this new knowledge. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc. [source] A practical guide to methods of parentage analysisMOLECULAR ECOLOGY RESOURCES, Issue 1 2010ADAM G. JONES Abstract The use of molecular techniques for parentage analysis has been a booming science for over a decade. The most important technological breakthrough was the introduction of microsatellite markers to molecular ecology, an advance that was accompanied by a proliferation and refinement of statistical techniques for the analysis of parentage data. Over the last several years, we have seen steady progress in a number of areas related to parentage analysis, and the prospects for successful studies continue to improve. Here, we provide an updated guide for scientists interested in embarking on parentage analysis in natural or artificial populations of organisms, with a particular focus on computer software packages that implement various methods of analysis. Our survey of the literature shows that there are a few established methods that perform extremely well in the analysis of most types of parentage studies. However, particular experimental designs or study systems can benefit from some of the less well-known computer packages available. Overall, we find that parentage analysis is feasible and satisfying in most systems, and we try to provide a simple roadmap to help other scientists navigate the confusing topography of statistical techniques. [source] A Decade of Deficits and Debt: Japanese Fiscal Policy and the Rise and Fall of the Fiscal Structural Reform Act of 1997PUBLIC BUDGETING AND FINANCE, Issue 1 2000James D. Savage Japanese budgetary and fiscal policy have experienced dramatic changes during the last several years, marked by the rise and fall of the Fiscal Structural Reform Act of 1997. This act altered the budgetary process with the goal of reducing Japan's rapidly growing deficit and debt. Yet the onset of recession in 1998 led Japan to engage again in large-scale deficit spending to stimulate the economy, and in the process discard its budget reforms. [source] FINDING AUTONOMY IN BIRTHBIOETHICS, Issue 1 2009THE OBSTETRICS AND GYNECOLOGY RISK RESEARCH GROUP: ABSTRACT Over the last several years, as cesarean deliveries have grown increasingly common, there has been a great deal of public and professional interest in the phenomenon of women ,choosing' to deliver by cesarean section in the absence of any specific medical indication. The issue has sparked intense conversation, as it raises questions about the nature of autonomy in birth. Whereas mainstream bioethical discourse is used to associating autonomy with having a large array of choices, this conception of autonomy does not seem adequate to capture concerns and intuitions that have a strong grip outside this discourse. An empirical and conceptual exploration of how delivery decisions ought to be negotiated must be guided by a rich understanding of women's agency and its placement within a complicated set of cultural meanings and pressures surrounding birth. It is too early to be ,for' or ,against' women's access to cesarean delivery in the absence of traditional medical indications , and indeed, a simple pro- or con- position is never going to do justice to the subtlety of the issue. The right question is not whether women ought to be allowed to choose their delivery approach but, rather, taking the value of women's autonomy in decision-making around birth as a given, what sorts of guidelines, practices, and social conditions will best promote and protect women's full inclusion in a safe and positive birth process. [source] New and emerging treatments for osteoporosisCLINICAL ENDOCRINOLOGY, Issue 3 2009Bart L. Clarke Summary A variety of new treatments for osteoporosis have become available within the last several years, and a number of emerging treatments remain in late clinical stage development. New and emerging treatments include more potent members, or more convenient formulations, of existing classes of therapy, but a number of the emerging treatments are first-generation compounds addressing specific therapeutic targets based on recent advances in understanding of basic bone biology. These new and emerging treatments include agents with anticatabolic effects, compounds with anabolic effects, and one agent possibly containing both anticatabolic and anabolic effects. The increasing variety of new and emerging treatments increases the possibility that effective therapy will be targeted to the specific needs of the individual patient. [source] | |||||||||||||||||||