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Central Element (central + element)
Selected AbstractsThe heel and toe of the cell's foot: A multifaceted approach for understanding the structure and dynamics of focal adhesionsCYTOSKELETON, Issue 11 2009Haguy Wolfenson Abstract Focal adhesions (FAs) are large clusters of transmembrane receptors of the integrin family and a multitude of associated cytoplasmic "plaque" proteins, which connect the extracellular matrix-bound receptors with the actin cytoskeleton. The formation of nearly stationary FAs defines a boundary between the dense and highly dynamic actin network in lamellipodium and the sparser and more diverse cytoskeletal organization in the lamella proper, creating a template for the organization of the entire actin network. The major "mechanical" and "sensory" functions of FAs; namely, the nucleation and regulation of the contractile, myosin-II-containing stress fibers and the mechanosensing of external surfaces depend, to a major extent, on the dynamics of molecular components within FAs. A central element in FA regulation concerns the positive feedback loop, based on the most intriguing feature of FAs; that is, their dependence on mechanical tension developing by the growing stress fibers. FAs grow in response to such tension, and rapidly disassemble upon its relaxation. In this article, we address the mechanistic relationships between the process of FA development, maturation and dissociation and the dynamic molecular events, which take place in different regions of the FA, primarily in the distal end of this structure (the "toe") and the proximal "heel," and discuss the central role of local mechanical forces in orchestrating the complex interplay between FAs and the actin system. Cell Motil. Cytoskeleton 66: 1017,1029, 2009. © 2009 Wiley-Liss, Inc. [source] Role of Apaf-1, a key regulator of apoptosis, in melanoma progression and chemoresistanceEXPERIMENTAL DERMATOLOGY, Issue 11 2005Mara Campioni Abstract:, Apoptosis protease-activating factor-1 (Apaf-1) is a key regulator of the mitochondrial apoptotic pathway, being the central element of the multimeric apoptosome formed by procaspase 9, cytochrome c, and Apaf-1 itself. In this review, the principal aspects about Apaf-1 gene structure and function, and its role in the apoptotic machinery, are described. Moreover, the most recent findings about the involvement of this molecule in melanoma progression and chemoresistance, as well as the clinico-pathological relevance of these findings in the treatment of this deadly disease, are reported. [source] A tale of two ,globalizations': capital flows from rich to poor in two eras of global financeINTERNATIONAL JOURNAL OF FINANCE & ECONOMICS, Issue 4 2006Moritz Schularick Abstract In this paper we take a comparative look at the patterns of capital flows from rich to poor countries in two eras of financial globalization. The paper extends recent research on the developmental effects of international financial integration, long-term trends in capital mobility and ,globalization in historical perspective'. Analysing the patterns of international financial integration in the three decades of the classical gold standard and after 1990 we show that investment in developing countries was a central element of 19th century financial globalization, but plays only a minor role today. The Lucas paradox of capital failing to flow from rich to poor has grown much stronger. In historical perspective, today's financial globalization is marked by massive diversification flows between high-income economies and a relative marginalization of less-developed economies. Copyright © 2006 John Wiley & Sons, Ltd. [source] Cooperation between social security and employment services: Evaluation of a reform strategy in the NetherlandsINTERNATIONAL SOCIAL SECURITY REVIEW, Issue 3 2002Jan Terpstra Since the early 1990s in the Netherlands a process of restructuring social security has been going on. A central element is the introduction of regional Centres of Work and Income, stimulating people living on benefits to return to paid work and making services more client,oriented. In these centres, social security organizations and employment services are supposed to cooperate. In practice this cooperation is hard to accomplish. The intended activation of clients is hardly realized. The problems encountered by this policy are characteristic of a top,down reform strategy in a corporatist welfare state like the Netherlands. [source] Annual planning of harvesting resources in the forest industryINTERNATIONAL TRANSACTIONS IN OPERATIONAL RESEARCH, Issue 2 2010David Bredström Abstract A cost-efficient use of harvesting resources is important in the forest industry. The main planning is carried out in an annual resource plan that is continuously revised. The harvesting operations are divided into harvesting and forwarding. The harvesting operation fells trees and puts them in piles in the harvest areas. The forwarding operation collects piles and moves them to storage locations adjacent to forest roads. These operations are conducted by machines (harvesters, forwarders and harwarders), and these are operated by crews living in cities/villages that are within some maximum distance from the harvest areas. Machines, harvest teams and harvest areas have different characteristics and properties and it is difficult to find the best possible match throughout the year. The aim of the planning is to find an annual plan with the lowest possible cost. The total cost is based on three parts: production cost, traveling cost and moving cost. The production cost is the cost for the harvesting and forwarding. The traveling cost is the cost for driving back and forwards (daily) from the home base to the harvest area and the moving cost is associated with moving the machines and equipment between harvest areas. The Forest Research Institute of Sweden (Skogforsk), together with a number of Swedish forest companies, has developed a decision support platform for the planning. One important element of this platform is that it should find high-quality plans within short computational times. One central element is an optimization model that integrates the assignment of machines to harvest areas and schedules the harvest areas during the year for each machine. The problem is complex and we propose a two-phase solution method where, first, we solve the assignment problem and, second, the scheduling. In order to be able to control the scheduling in phase 1 as well, we have introduced an extra cost component that controls the geographical distribution of harvest areas for each machine in phase 1. We have tested the solution approach on a case study from one of the larger Swedish forest companies. This case study involves 46 machines and 968 harvest areas representing a log volume of 1.33 million cubic meters. We describe some numerical results and experience from the development and tests. [source] Review article: Kidney dendritic cells: Their role in homeostasis, inflammation and transplantationNEPHROLOGY, Issue 7 2009NATASHA M ROGERS SUMMARY: There is definitive experimental proof that a lattice of dendritic cells (DC) exist within the renal parenchyma. Kidney-resident DC (KDC) are an important constituent of passenger leucocytes that initiate the direct component of allograft rejection in transplantation and form a central element of the innate immune response following injurious stimuli to the kidney. DC are recruited to the kidney in pathophysiological states such as glomerulonephritis and ischaemia,reperfusion injury. However, the exact mechanism for engaging and attracting DC to infectious and transplant antigens, and whether specific DC subsets are involved remains unresolved. In addition, the extent to which resident and infiltrating DC contribute to the propagation of injury or rejection is also unclear. Despite consistently expanding published work regarding DC location, phenotype and function, there are a number of deficiencies in our knowledge base, particularly in relation to KDC. [source] The center function on treesNETWORKS: AN INTERNATIONAL JOURNAL, Issue 2 2001F. R. McMorris Abstract When (X, d) is a finite metric space and , = (x1, ,, xk) , Xk, a central element for , is an element x of X for which max{d (x, xi): i = 1, ,, k} is minimum. The function that returns the set of all central elements for any tuple , is called the center function on X. In this article, the center function on finite trees is characterized. © John Wiley & Sons, Inc. [source] Trust Your Compatriots, but Count Your Change: The Roles of Trust, Mistrust and Distrust in DemocracyPOLITICAL STUDIES, Issue 2 2008Patti Tamara Lenard Although trust is clearly central to human relations of all kinds, it is less clear whether there is a role for trust in democratic politics. In this article, I argue that trust is central to democratic institutions as well as to democratic political participation, and that arguments which make distrust the central element of democracy fail. First, I argue for the centrality of trust to the democratic process. The voluntary compliance that is central to democracies relies on trust, along two dimensions: citizens must trust their legislators to have the national interest in mind and citizens must trust each other to abide by democratically established laws. Second, I refute arguments that place distrust at the centre of democratic institutions. I argue, instead, that citizens must be vigilant with respect to their legislators and fellow citizens; that is, they must be willing to ensure that the institutions are working fairly and that people continue to abide by shared regulations. This vigilance , which is reflected both in a set of institutions as well as an active citizenry , is motivated by an attitude termed ,mistrust'. Mistrust is a cautious attitude that propels citizens to maintain a watchful eye on the political and social happenings within their communities. Moreover, mistrust depends on trust: we trust fellow citizens to monitor for abuses of our own rights and privileges just as we monitor for abuses of their rights and privileges. Finally, I argue that distrust is inimical to democracy. We are, consequently, right to worry about widespread reports of trust's decline. Just as distrust is harmful to human relations of all kinds, and just as trust is central to positive human relations of all kinds, so is distrust inimical to democracy and trust central to its flourishing. [source] Focusing on Customer Time in Field Service: A Normative ApproachPRODUCTION AND OPERATIONS MANAGEMENT, Issue 2 2007Aruna Apte Although customer convenience should be rightfully considered a central element in field services, the customer experience suggests that service enterprises rarely take the customer's preferred time into account in making operational and scheduling decisions. In this paper we present the results of our exploratory research into two interrelated topics: the explicit inclusion of customer time in nonemergency field service delivery decisions and the analysis of trade-off between the customer's convenience and field service provider's cost. Based on prior research in service quality we identify and illustrate two time-based performance metrics that are particularly appropriate for assessing service quality in nonemergency field services: performance and conformance quality. To determine vehicle routes, we develop a hybrid heuristic derived from the existing and proven heuristic methods. A numerical example closely patterned after real-life data is generated and used within a computational experiment to investigate alternate policies for promise time windows. Our experiment shows that over a reasonable range of customer cost parameters the policy of shorter promise time windows reduces the combined total cost incurred by the provider and the customers and should be considered a preferred policy by the field service provider. Managerial implications of this result are discussed. [source] Synthesis and Pharmacological Evaluation of 8- and 9-Substituted Benzolactam-V8 Derivatives as Potent Ligands for Protein Kinase,C, a Therapeutic Target for Alzheimer's DiseaseCHEMMEDCHEM, Issue 3 2006Ulrich Abstract A central element in the pathophysiology of Alzheimer's disease (AD) is the formation of amyloid plaques, which result from abnormal processing of the amyloid precursor protein (APP). The processing of APP is largely provided by three key enzymes, namely the ,-, ,-, and ,-secretases. As the latter two contribute to the formation of neurotoxic A, fragments while ,-secretase does not, a decrease in the amyloidogenic products can be brought about either by inhibition of the ,- and ,-secretases or through the activation of ,-secretase. It is now known that the activation of protein kinase,C (PKC) enhances ,-secretase activity and therefore represents a possible target for the development of agents urgently needed for the treatment of this devastating neurodegenerative disorder. In the present study, new benzolactam-V8-based PKC activators were synthesized and tested for their binding affinity toward PKC,. All compounds tested showed binding values in the nanomolar concentration range. In accordance with previous publications, 9-substitution dramatically increased PKC binding affinity in comparison with the corresponding 8-substituted analogues. In addition to the location of the side chain on the aromatic ring, the binding affinities of these benzolactams were found to depend on the orientation, length, and electronic properties of this appendage. An interesting decrease in binding affinity was found for the 9-thienyl analogue 13, suggesting adverse electronic interactions of the sulfur atom with PKC or parts of the cellular membrane. [source] EXCITATION,CONTRACTION COUPLING FROM THE 1950s INTO THE NEW MILLENNIUMCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2006AF Dulhunty SUMMARY 1Excitation,contraction coupling is broadly defined as the process linking the action potential to contraction in striated muscle or, more narrowly, as the process coupling surface membrane depolarization to Ca2+ release from the sarcoplasmic reticulum. 2We now know that excitation,contraction coupling depends on a macromolecular protein complex or ,calcium release unit'. The complex extends the extracellular space within the transverse tubule invaginations of the surface membrane, across the transverse tubule membrane into the cytoplasm and then across the sarcoplasmic reticulum membrane and into the lumen of the sarcoplasmic reticulum. 3The central element of the macromolecular complex is the ryanodine receptor calcium release channel in the sarcoplasmic reticulum membrane. The ryanodine receptor has recruited a surface membrane L-type calcium channel as a ,voltage sensor' to detect the action potential and the calcium-binding protein calsequestrin to detect in the environment within the sarcoplasmic reticulum. Consequently, the calcium release channel is able to respond to surface depolarization in a manner that depends on the Ca2+ load within the calcium store. 4The molecular components of the ,calcium release unit' are the same in skeletal and cardiac muscle. However, the mechanism of excitation,contraction coupling is different. The signal from the voltage sensor to ryanodine receptor is chemical in the heart, depending on an influx of external Ca2+ through the surface calcium channel. In contrast, conformational coupling links the voltage sensor and the ryanodine receptor in skeletal muscle. 5Our current understanding of this amazingly efficient molecular signal transduction machine has evolved over the past 50 years. None of the proteins had been identified in the 1950s; indeed, there was debate about whether the molecules involved were, in fact, protein. Nevertheless, a multitude of questions about the molecular interactions and structures of the proteins and their interaction sites remain to be answered and provide a challenge for the next 50 years. [source] Wnt11 and Wnt7a are up-regulated in association with differentiation of cardiac conduction cells in vitro and in vivoDEVELOPMENTAL DYNAMICS, Issue 4 2003Jacqueline Bond Abstract The heart beat is coordinated by a precisely timed sequence of action potentials propagated through cells of the conduction system. Previously, we have shown that conduction cells in the chick embryo are derived from multipotent, cardiomyogenic progenitors present in the looped, tubular heart. Moreover, analyses of heterogeneity within myocyte clones and cell birth dating have indicated that elaboration of the conduction system occurs by ongoing, localized recruitment from within this multipotent pool. In this study, we have focused on a potential role for Wnt signaling in development of the cardiac conduction system. Treatment of embryonic myocytes from chick with endothelin-1 (ET-1) has been shown to promote expression of markers of Purkinje fiber cells. By using this in vitro model, we find that Wnt11 are Wnt7a are up-regulated in association with ET-1 treatment. Moreover, in situ hybridization reveals expression, although not temporal coincidence of, Wnt11 and Wnt7a in specialized tissues in the developing heart in vivo. Specifically, whereas Wnt11 shows transient and prominent expression in central elements of the developing conduction system (e.g., the His bundle), relative increases in Wnt7a expression emerge at sites consistent with the location of peripheral conduction cells (e.g., subendocardial Purkinje fibers). The patterns of Wnt11 and Wnt7a expression observed in vitro and in the embryonic chick heart appear to be consistent with roles for these two Wnts in differentiation of cardiac conduction tissues. Development Dynamics 227:536,543, 2003. © 2003 Wiley-Liss, Inc. [source] The Micro-politics of Gendering in NetworkingGENDER, WORK & ORGANISATION, Issue 2 2009Yvonne Benschop Networking processes contribute to the perpetuation of gender inequalities in everyday practices in organizations. This article examines the implications of the conceptualization of gender as practice for social network theory. The three central elements of this critical feminist approach to networking are the study of agency, identity construction and the micro-political processes of networking and gendering. To illustrate that networking practices are gendering practices, that there are various manifestations of those practices, and the way in which networking and gendering are intertwined, the networking practices of four white, Dutch female and male account managers are discussed. This micro-political analysis suggests that networking does not necessarily reinforce gender inequality, which opens up the possibility of examining which combinations of networking and gendering contribute to changing the gender order. [source] Which Candidate Selection Method is the Most Democratic?1GOVERNMENT AND OPPOSITION, Issue 1 2009Gideon Rahat This article suggests guidelines for identifying the ramifications of central elements of candidate selection methods for various democratic dimensions , participation, competition, representation and responsiveness , and analyses their possible role in supplying checks and balances. It proposes employing a three-stage candidate selection method: in the first stage a small committee appoints candidates to a shortlist; in the second stage a selected party agency may add or remove candidates using a special procedure (absolute majority vote, for example) and also ratify the re-adoption of incumbent candidates; and, finally, party members select candidates for safe seats or safe list positions among the proposed candidates. The article also recommends employing moderate requirements for candidacy; the use of a non-majoritarian voting method; and allowing the national centre a say in candidate selection. [source] Illegal Migration: What Can We Know And What Can We Explain?INTERNATIONAL MIGRATION REVIEW, Issue 3 2004The Case of Germany Methodological problems in the study of illegal migration as defined in this article relate to questions of indicators for illegal migration, with special reference to Germany. It is argued and demonstrated that illegal immigrants are traceable, to some degree, in official statistics and that these can be analyzed for trends. In present-day migration processes, illegal immigration frequently is undertaken with the support of human smugglers. The analysis of the social organization of different forms of smuggling is the other main focus of the article. From a methodological point of view, the literature and public discourse lack adequate concepts for describing and explaining the social organization of human smuggling. The theory of organized crime as a main actor in human smuggling is criticized. The study borrows concepts from market and networks theory and applies these to different forms of human smuggling and illegal migration. The social and technological organization of smuggling is under constant pressure to adapt to new conditions. The dynamism for this change results mainly from an "arms race" between smugglers and law enforcement. Since control over territory and population are central elements of state sovereignty, the state cannot simply withdraw from this race. [source] Constitutionalizing Inequality and the Clash of GlobalizationsINTERNATIONAL STUDIES REVIEW, Issue 2 2002Stephen Gill Intensified inequalities, social dislocations and human insecurity have coincided with a redefinition of the political in the emerging world order. Part of this redefinition involves the emergence of new constitutionalism. New constitutionalism limits democratic control over central elements of economic policy and regulation by locking in future governments to liberal frameworks of accumulation premised on freedom of enterprise. New political "limits of the possible" are also redefined by a "clash of globalizations" as new constitutionalism and more generally "globalization from above" is contested from below by nationalists, populists and fundamentalists as well as diverse progressive movements in innovative forms of global political agency. [source] The center function on treesNETWORKS: AN INTERNATIONAL JOURNAL, Issue 2 2001F. R. McMorris Abstract When (X, d) is a finite metric space and , = (x1, ,, xk) , Xk, a central element for , is an element x of X for which max{d (x, xi): i = 1, ,, k} is minimum. The function that returns the set of all central elements for any tuple , is called the center function on X. In this article, the center function on finite trees is characterized. © John Wiley & Sons, Inc. [source] The Philosophy of Social Science: Metaphysical and EmpiricalPHILOSOPHY COMPASS (ELECTRONIC), Issue 6 2007Francesco Guala Ontological debates have always been prominent in the philosophy of social science. Philosophers have typically conceived of such debates as pre-scientific attempts to reform social scientific practice, rather than as post-scientific reflections on a firm body of scientific knowledge. Two celebrated contemporary research programs in social ontology , collective intentionality and evolutionary game theory , also follow this approach. In this paper I illustrate their central elements and criticize their weak empirical foundations. I finish by reviewing some work that combines empirical evidence with theoretical reflection, and suggest that it constitutes the way forward in the philosophy of social science. [source] CIVIL SERVICE REFORM IN THE UK, 1999,2005: REVOLUTIONARY FAILURE OR EVOLUTIONARY SUCCESS?PUBLIC ADMINISTRATION, Issue 2 2007TONY BOVAIRD In December 1999, the UK Civil Service Management Board agreed an internal reform programme, complementing the more externally-oriented ,modernizing government' programme, to bring about major changes in the functioning of the civil service ,,step change' rather than continuous improvement. This paper suggests that the aims of the reform programme were only partially achieved. While some step changes did indeed occur, even such central elements of reform as ,joined-up' working with other public organizations were still only at an initial stage some three years later and others , for example, business planning and performance management systems , have taken 20 years to achieve acceptance within the civil service. It appears that examples of meteoric change are rare in the civil service , the reality of the changes are better characterized as ,evolution' and ,continuous improvement' than ,revolution' and ,step change'. [source] Party Identification and Core Political ValuesAMERICAN JOURNAL OF POLITICAL SCIENCE, Issue 4 2005Paul Goren Party identification and core political values are central elements in the political belief systems of ordinary citizens. Are these predispositions related to one another? Does party identification influence core political values or are partisan identities grounded in such values? This article draws upon theoretical works on partisan information processing and value-based reasoning to derive competing hypotheses about whether partisanship shapes political values or political values shape partisanship. The hypotheses are tested by using structural equation modeling techniques to estimate dynamic models of attitude stability and constraint with data from the 1992,94,96 National Election Study panel survey. The analyses reveal that partisan identities are more stable than the principles of equal opportunity, limited government, traditional family values, and moral tolerance; party identification constrains equal opportunity, limited government, and moral tolerance; and these political values do not constrain party identification. [source] Conducting fieldwork with Tarieng communities in southern Laos: Negotiating discursive spaces between neoliberal dogmas and Lao socialist ideologyASIA PACIFIC VIEWPOINT, Issue 2 2010Steeve Daviau Abstract Based on research with ethnic minorities in Laos aimed at understanding how they cope with and negotiate political and economic ,double domination', this article examines the experiences of prolonged fieldwork in a remote Tarieng area in the Annam Range, southern Laos. After briefly reviewing Lao ethnographical policy and practice regarding ethnic minorities, I introduce the Tarieng people. I detail how I initially gained access to these local communities via long-term engagement with a range of development project initiatives. Then, after eight years of conducting such fieldwork in a Tarieng area ,below the radar of the state', I managed to obtain official authorisations to continue research as a graduate student. In this new position, I accessed the field via different negotiations with central, provincial and local official bureaucracies. After detailing this process, back in the field I reveal my strategies to create a discursive space that has allowed me to access dissident Tarieng voices and agency. Finally, I highlight four central elements that have continued to shape my field research: language proficiency, working with research assistants, awareness of political relations and cultural sensitivity, and ethical concerns. These have emerged while the possibilities and constraints of political engagement with the Tarieng people are explored. [source] | |||||||||||||||||||