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Selected AbstractsComparative and developmental study of the immune system in XenopusDEVELOPMENTAL DYNAMICS, Issue 6 2009Jacques Robert Abstract Xenopus laevis is the model of choice for evolutionary, comparative, and developmental studies of immunity, and invaluable research tools including MHC-defined clones, inbred strains, cell lines, and monoclonal antibodies are available for these studies. Recent efforts to use Silurana (Xenopus) tropicalis for genetic analyses have led to the sequencing of the whole genome. Ongoing genome mapping and mutagenesis studies will provide a new dimension to the study of immunity. Here we review what is known about the immune system of X. laevis integrated with available genomic information from S. tropicalis. This review provides compelling evidence for the high degree of similarity and evolutionary conservation between Xenopus and mammalian immune systems. We propose to build a powerful and innovative comparative biomedical model based on modern genetic technologies that takes take advantage of X. laevis and S. tropicalis, as well as the whole Xenopus genus. Developmental Dynamics 238:1249,1270, 2009. © 2009 Wiley-Liss, Inc. [source] The production of n -3 long-chain polyunsaturated fatty acids in transgenic plantsEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 11 2006Johnathan A. Napier Abstract Long-chain polyunsaturated fatty acids (LC-PUFA) now have a proven role in human health and nutrition, including the n -3 forms normally found in fish oils. Unfortunately, global fish stocks are now more than ever subject to over-fishing and environmental pollution, indicating the need for an alternative source of fish oils. Recent efforts have focussed on the production of LC-PUFA in transgenic plants to provide a sustainable and clean source of fish oils. The current progress in this area is considered, as well as the bottlenecks that remain to be overcome. [source] Stereocontrolled Preparation of Fully Substituted Cyclopentanes: Relevance to Total SynthesisEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2009Brian Heasley Abstract This Microreview aims to identify important advances in the asymmetric synthesis of fully substituted five-membered carbocyclic ring systems. Recent efforts directed towards the intricate and densely functionalized core substructures of three distinct classes of cyclopentane-based natural products will be examined. Strategies featuring high levels of stereocontrol and/or conciseness in the total number of synthetic steps required to access complex natural product ring fragments are highlighted. Stereoselective Diels,Alder cycloaddition approaches to access functionalized norbornene intermediates as latent chiral cyclopentanes in the tradition of Corey's elegant prostaglandin studies are a recurring theme. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Design, Synthesis and Evaluation of Serine Protease Inhibitor AnaloguesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2007Laila Kamoune Abstract Recent efforts in the field of thrombin inhibitor research have focused on the identification of pyrazinone-containing compounds. In this manuscript we describe the synthesis of the new pyrazinones 12,36. All the targets were fully characterised and screened for serine protease inhibition. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] State Policies, Enterprise Dynamism, and Innovation System in Shanghai, ChinaGROWTH AND CHANGE, Issue 4 2007WEIPING WU ABSTRACT Today rapidly growing economies depend more on the creation, acquisition, distribution, and use of knowledge. As such, strategies for enhancing research and innovation capabilities have come to occupy a more important position in many developing nations, including China. Already the leading production center, and often seen as China's economic locomotive, Shanghai is striving aggressively to retain its national preeminence and has launched concerted efforts to increase local innovative output. The primary purpose of this paper is to understand how state-led efforts have fared in promoting technology innovation. By situating the city in the national and global context, the paper shows that Shanghai has gained a substantial lead in developing an innovation environment with extensive global linkages and leading research institutions. Recent efforts in building up the research and innovation capacity of the enterprise sector have begun to show progress. Although firms are enthusiastic about its future as an innovation center, Shanghai continues to face challenges of inadequate protection of intellectual property, lack of venture capital investment, and the tightening supply of highly qualified knowledge workers. [source] A Pain Severity,Hypothalamic,Pituitary,Adrenocortical Axis Interaction: The Effects on Pain Pathways,JOURNAL OF APPLIED BIOBEHAVIORAL RESEARCH, Issue 1 2007John P. Garofalo Recent efforts have identified psychosocial and biological factors influencing the pathogenesis of chronic pain. The present study attempted to identify whether these two variables interact and, in turn, represent an underlying mechanism in the transition from acute to chronic pain. Salivary cortisol samples were collected upon waking up and 20 minutes later daily for 2 weeks from acute pain patients. Analyses revealed a direct relationship between pain severity and hypothalamic,pituitary,adrenocortical activity for temporomandibular disorder, and a negative relationship between these variables for low back pain populations. These results highlight the possible interaction between neuroendocrine and psychological factors to increase the risk for chronic pain. [source] Recombination and lineage-specific gene loss in the aflatoxin gene cluster of Aspergillus flavusMOLECULAR ECOLOGY, Issue 23 2009GEROMY G. MOORE Abstract Aflatoxins produced by Aspergillus flavus are potent carcinogens that contaminate agricultural crops. Recent efforts to reduce aflatoxin concentrations in crops have focused on biological control using nonaflatoxigenic A. flavus strains AF36 (=NRRL 18543) and NRRL 21882 (the active component of afla-guard®). However, the evolutionary potential of these strains to remain nonaflatoxigenic in nature is unknown. To elucidate the underlying population processes that influence aflatoxigenicity, we examined patterns of linkage disequilibrium (LD) spanning 21 regions in the aflatoxin gene cluster of A. flavus. We show that recombination events are unevenly distributed across the cluster in A. flavus. Six distinct LD blocks separate late pathway genes aflE, aflM, aflN, aflG, aflL, aflI and aflO, and there is no discernable evidence of recombination among early pathway genes aflA, aflB, aflC, aflD, aflR and aflS. The discordance in phylogenies inferred for the aflW/aflX intergenic region and two noncluster regions, tryptophan synthase and acetamidase, is indicative of trans-species evolution in the cluster. Additionally, polymorphisms in aflW/aflX divide A. flavus strains into two distinct clades, each harbouring only one of the two approved biocontrol strains. The clade with AF36 includes both aflatoxigenic and nonaflatoxigenic strains, whereas the clade with NRRL 21882 comprises only nonaflatoxigenic strains and includes all strains of A. flavus missing the entire gene cluster or with partial gene clusters. Our detection of LD blocks in partial clusters indicates that recombination may have played an important role in cluster disassembly, and multilocus coalescent analyses of cluster and noncluster regions indicate lineage-specific gene loss in A. flavus. These results have important implications in assessing the stability of biocontrol strains in nature. [source] Colonial Legacy in African Museology: The Case of the Ghana National MuseumMUSEUM ANTHROPOLOGY, Issue 1 2008Arianna Fogelman Abstract African museums were largely founded during the colonial era to house artifacts amassed by imperial agents whose contemporaneous understandings of race, evolution and culture led them to believe local populations were "backward" or otherwise "primitive." Today in the hands of independent governments, scholars frequently cite "colonial legacy" to explain these institutions' continued irrelevance to the local communities they purport to serve. Recent efforts to "localize" African museums have proceeded without a critical analysis of the "colonial legacy" concept, which both denies local agency and cultural malleability in the museum concept, as demonstrated with the case of the Ghana National Museum. [source] Recent developments in the use of two-photon polymerization in precise 2D and 3D microfabrications,POLYMERS FOR ADVANCED TECHNOLOGIES, Issue 2 2006Kwang-Sup Lee Abstract The use of two-photon polymerization (TPP) initiated by a photosensitizer's non-linear two-photon absorption in two- and three-dimensional (2D and 3D) microfabrications for various photonic applications has been intensively studied. Since TPP emerged as a new technology over a decade ago, a large variety of micro-objects including 3D micro-optical components, micromechanical devices, and 3D photonic crystals have been fabricated using TPP with a high spatial resolution of approximately submicron scale to 100,nm. Recent efforts have been made to improve the fabrication efficiency and precision of micro-objects obtained with TPP; in particular, many studies have been carried out with the aim of developing efficient two-photon absorbing chromophores. In this article, efforts to develop highly efficient two-photon absorbing materials and also describe recent attempts to enhance the resolution and improve the fabrication efficiency of nanofabrications based on two-photon polymerization are discussed. Copyright © 2006 John Wiley & Sons, Ltd. [source] "Roll Back Malaria, Roll in Development"?POPULATION AND DEVELOPMENT REVIEW, Issue 1 2009Reassessing the Economic Burden of Malaria Recent efforts to mobilize support for malaria control have highlighted the economic burden of malaria and the value of malaria control for generating economic development. These claims have a long history. Beginning in the early twentieth century, they became the primary justification for malaria-control programs in the American South and in other parts of the globe, including British India. Economists conducted none of these studies. Following World War II and the development of new anti-malarial drugs and pesticides, including DDT, malaria control and eradication were increasingly presented as instruments for eliminating economic underdevelopment. By the 1960s, however, economists and demographers began to raise serious substantive and methodological questions about the basis of these claims. Of particular concern was the role of rapid population growth, resulting in part from the decline of malaria mortality, in undermining the short-term economic gains achieved through malaria control. Despite these concerns, malaria continues to be presented as an economic problem in the work of Jeffrey Sachs and others, justifying massive investments in malaria control. The methodological basis of these claims is examined. The paper concludes that while malaria takes a dreadful toll in human lives and causes significant economic losses for individuals, families, and some industries, the evidence linking malaria control to national economic growth remains unconvincing. In addition, the evidence suggests that there are potential costs to justifying malaria-eradication campaigns on macroeconomic grounds. [source] Organic Nanomaterials: Morphological Control for Charge Stabilization and Charge TransportCHEMISTRY - AN ASIAN JOURNAL, Issue 6 2009P. Pramod Dr. Abstract How grows it? Organic nanostructured materials have been projected as active components in optoelectronic devices. Recent efforts in manipulating the morphology of organic nanomaterials, particularly on their size and shape, are summarized in this Focus Review. Potential application of organic nanostructured materials in charge stabilization and transporting are also discussed. Chromophoric systems with proper recognition motifs can organize into well-defined arrays forming supramolecular assemblies and further into nanoscopic materials. The optical and electrical properties of organic nanomaterials depend upon the stacking modes of organic molecules and also on the kind of interaction between different chromophore units (such as H- and J- type aggregates). These types of aggregates can dramatically alter the opto-electronic properties of organic nanostructures. Hence efforts are currently directed towards manipulating the morphology of organic nanomaterials, particularly on their size and shape by adopting different techniques and these aspects are discussed. Recent studies have shown that such nanostructures are extremely important in the development of optoelectronic systems such as photovoltaic devices. This Focus Review also discusses the potential application of organic nanomaterials in charge stabilization and transport. [source] Simulation of resource synchronization in a dynamic real-time distributed computing environmentCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 14 2004Chen Zhang Abstract Today, more and more distributed computer applications are being modeled and constructed using real-time principles and concepts. In 1989, the Object Management Group (OMG) formed a Real-Time Special Interest Group (RT SIG) with the goal of extending the Common Object Request Broker Architecture (CORBA) standard to include real-time specifications. This group's most recent efforts have focused on the requirements of dynamic distributed real-time systems. One open problem in this area is resource access synchronization for tasks employing dynamic priority scheduling. This paper presents two resource synchronization protocols that the authors have developed which meet the requirements of dynamic distributed real-time systems as specified by Dynamic Scheduling Real-Time CORBA (DSRT CORBA). The proposed protocols can be applied to both Earliest Deadline First (EDF) and Least Laxity First (LLF) dynamic scheduling algorithms, allow distributed nested critical sections, and avoid unnecessary runtime overhead. In order to evaluate the performance of the proposed protocols, we analyzed each protocol's schedulability. Since the schedulability of the system is affected by numerous system configuration parameters, we have designed simulation experiments to isolate and illustrate the impact of each individual system parameter. Simulation experiments show the proposed protocols have better performance than one would realize by applying a schema that utilizes dynamic priority ceiling update. Copyright © 2004 John Wiley & Sons, Ltd. [source] IS TIGHTER FISCAL POLICY EXPANSIONARY UNDER FISCAL DOMINANCE?: HYPERCROWDING OUT IN LATIN AMERICACONTEMPORARY ECONOMIC POLICY, Issue 2 2010WILLIAM C. GRUBEN Hypercrowding out occurs when fiscally dominated governments' domestic credit demands are so intrusive to a nation's financial system that a move toward fiscal surplus lowers interest rates and increases growth. We sample nine Latin American countries to test for these relationships. The impulse-response results of vector error correction models, six nations test positive for these two connections, suggesting market concern despite recent efforts toward fiscal balance. (JEL E430, E620, O230, O540) [source] Effects of species diversity on disease riskECOLOGY LETTERS, Issue 4 2006F. Keesing Abstract The transmission of infectious diseases is an inherently ecological process involving interactions among at least two, and often many, species. Not surprisingly, then, the species diversity of ecological communities can potentially affect the prevalence of infectious diseases. Although a number of studies have now identified effects of diversity on disease prevalence, the mechanisms underlying these effects remain unclear in many cases. Starting with simple epidemiological models, we describe a suite of mechanisms through which diversity could increase or decrease disease risk, and illustrate the potential applicability of these mechanisms for both vector-borne and non-vector-borne diseases, and for both specialist and generalist pathogens. We review examples of how these mechanisms may operate in specific disease systems. Because the effects of diversity on multi-host disease systems have been the subject of much recent research and controversy, we describe several recent efforts to delineate under what general conditions host diversity should increase or decrease disease prevalence, and illustrate these with examples. Both models and literature reviews suggest that high host diversity is more likely to decrease than increase disease risk. Reduced disease risk with increasing host diversity is especially likely when pathogen transmission is frequency-dependent, and when pathogen transmission is greater within species than between species, particularly when the most competent hosts are also relatively abundant and widespread. We conclude by identifying focal areas for future research, including (1) describing patterns of change in disease risk with changing diversity; (2) identifying the mechanisms responsible for observed changes in risk; (3) clarifying additional mechanisms in a wider range of epidemiological models; and (4) experimentally manipulating disease systems to assess the impact of proposed mechanisms. [source] COMMENT ON NAVIGATING REFORMS: LESSONS FROM INDIA, THE 2008 WINCOTT LECTURE, GIVEN BY ARUN SHOURIEECONOMIC AFFAIRS, Issue 3 2009Razeen Sally Economic growth in India has been impressive in recent years. However, development has largely by-passed agriculture and labour-intensive industry, the sectors with the most potential to drive up living standards in the long term. Despite welcome recent efforts at reform, large parts of the Indian economy continue to be hindered by poor governance and over-regulation. [source] Multifunctional host defense peptides: antiparasitic activitiesFEBS JOURNAL, Issue 22 2009Amram Mor Whereas significant knowledge is accumulating on the antibacterial and antifungal properties of host defense peptides (HDPs) and their synthetic mimics, much less is known of their activities against parasites. A variety of in vitro and in vivo antiparasitic assays suggest that these notorious antimicrobial compounds could represent a powerful tool for the development of novel drugs to fight parasites in the vertebrate host or to complement current therapeutic strategies, albeit the fact that HDPs essentially act by nonspecific mechanisms casts serious doubt on their ability to exert sufficient selectivity to be considered ideal candidates for drug development. This minireview summarizes recent efforts to assess the antiparasitic properties of HDPs and their synthetic derivatives, focusing on two of the most used models ,Plasmodium and Leishmania species , for antiparasitic assays against the different development stages. [source] Design of Multiresponsive Hydrogel Particles and AssembliesADVANCED FUNCTIONAL MATERIALS, Issue 11 2010Grant R. Hendrickson Abstract In the realm of soft nanotechnology, hydrogel micro- and nanoparticles represent a versatile class of responsive materials. Over the last decade, our group has investigated the synthesis and physicochemical properties of a variety of synthetic hydrogel particles. From these efforts, several particle types have emerged with potentially enabling features for biological applications, including nanogels for targeted drug delivery, microlenses for biosensing, and coatings for biomedical devices. For example, core/shell nanogels have been used to encapsulate and deliver small interfering RNA to ovarian cancer cells; nanogels used in this fashion may improve therapeutic outcomes for a variety of macromolecular therapeutics. Microgels arranged as multilayers on implantable biomaterials greatly minimize the host inflammatory response to the material. Furthermore, the triggered release of drugs (i.e., insulin) has been demonstrated from similar assemblies. The goal of this feature article is to highlight developments in the design of responsive microgels and nanogels in the context of our recent efforts and in relation to the community that has grown up around this fascinating class of materials. [source] A domain decomposition approach to finite volume solutions of the Euler equations on unstructured triangular meshesINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 6 2001Victoria Dolean Abstract We report on our recent efforts on the formulation and the evaluation of a domain decomposition algorithm for the parallel solution of two-dimensional compressible inviscid flows. The starting point is a flow solver for the Euler equations, which is based on a mixed finite element/finite volume formulation on unstructured triangular meshes. Time integration of the resulting semi-discrete equations is obtained using a linearized backward Euler implicit scheme. As a result, each pseudo-time step requires the solution of a sparse linear system for the flow variables. In this study, a non-overlapping domain decomposition algorithm is used for advancing the solution at each implicit time step. First, we formulate an additive Schwarz algorithm using appropriate matching conditions at the subdomain interfaces. In accordance with the hyperbolic nature of the Euler equations, these transmission conditions are Dirichlet conditions for the characteristic variables corresponding to incoming waves. Then, we introduce interface operators that allow us to express the domain decomposition algorithm as a Richardson-type iteration on the interface unknowns. Algebraically speaking, the Schwarz algorithm is equivalent to a Jacobi iteration applied to a linear system whose matrix has a block structure. A substructuring technique can be applied to this matrix in order to obtain a fully implicit scheme in terms of interface unknowns. In our approach, the interface unknowns are numerical (normal) fluxes. Copyright © 2001 John Wiley & Sons, Ltd. [source] The evolution of, and revolution in, land surface schemes designed for climate modelsINTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 5 2003A. J. Pitman Abstract The land surface is a key component of climate models. It controls the partitioning of available energy at the surface between sensible and latent heat, and it controls the partitioning of available water between evaporation and runoff. The land surface is also the location of the terrestrial carbon sink. Evidence is increasing that the influence of the land surface is significant on climate and that changes in the land surface can influence regional- to global-scale climate on time scales from days to millennia. Further, there is now a suggestion that the terrestrial carbon sink may decrease as global temperatures increase as a consequence of rising CO2 levels. This paper provides the theoretical background that explains why the land surface should play a central role in climate. It also provides evidence, sourced from climate model experiments, that the land surface is of central importance. This paper then reviews the development of land surface models designed for climate models from the early, very simple models through to recent efforts, which include a coupling of biophysical processes to represent carbon exchange. It is pointed out that significant problems remain to be addressed, including the difficulties in parameterizing hydrological processes, root processes, sub-grid-scale heterogeneity and biogeochemical cycles. It is argued that continued development of land surface models requires more multidisciplinary efforts by scientists with a wide range of skills. However, it is also argued that the framework is now in place within the international community to build and maintain the latest generation of land surface models. Further, there should be considerable optimism that consolidating the recent rapid advances in land surface modelling will enhance our capability to simulate the impacts of land-cover change and the impacts of increasing CO2 on the global and regional environment. Copyright © 2003 Royal Meteorological Society [source] Quality preservation in chilled and frozen fish products by employment of slurry ice and natural antioxidantsINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 8 2009Isabel Medina Summary Fish products are known to provide high levels of constituents important for the human diet. At the same time, wild and farmed fish species are highly perishable products, the quality and freshness of which rapidly declines post-mortem. Accordingly, efficient storage and processing technologies need to be employed to reduce postmortem quality losses until the product reaches the consumer. The present review covers recent efforts carried out on some new and advanced strategies related to chilled and frozen storage. In the first part, research concerning the use of binary systems (slurry ice) is reviewed, this focussed on the commercialisation of fresh fish products as such or to its employment as raw material for processing. Then, the application of exogenous antioxidants to ensure retention of high quality is addressed; in this part, special attention is accorded to the endogenous antioxidant content retention and to the antioxidant/pro-oxidant balance in fish foods. [source] Application of labour and employment law beyond the contract of employmentINTERNATIONAL LABOUR REVIEW, Issue 1-2 2007Mark FREEDLAND The personal scope of employment law is the subject of much ongoing debate. Arguing that an exclusively contractual analysis of this domain is unsatisfactory, the author constructs a European-based empirical typology distinguishing the personal work relations of "standard employees", public officials, "liberal professions", individual entrepreneurial workers, marginal workers, and labour market entrants. These categories and their inter-relationships are then analysed dynamically in terms of "personal work nexuses" - a concept encompassing complex legal ramifications beyond the contractual framework. The conclusions highlight the value of this analytical approach to recent efforts by the ILO and the European Commission to "modernize" labour law. [source] OECD Efforts to Address the Measurement and Policy Challenges Posed by the Information SocietyINTERNATIONAL STATISTICAL REVIEW, Issue 1 2003Andrew W. Wyckoff Summary The OECD has acted as a forum for the discussion of policies regarding the information society for over 20-years, producing guidelines and recommendations in areas such as privacy of personal information, computer security, cryptography, regulatory reform of communications, and most recently on-line consumer protection and the taxation of e-commerce. By and large, this work was undertaken without the benefit of statistical measures. But the economic performance of a number of OECD Member countries during the 1990s underscores that the policy challenges being posed by the information society are increasingly economic in nature,how ICT is affecting productivity, growth rates, inflation, labour markets etc.,necessitating the need for statistically rigorous data. This paper outlines how recent efforts by national statistical offices to improve this situation have allowed researchers to gain new insight into the economic impact associated with ICTs and applications like e-commerce, leading to a number of policy recommendations as to how best to exploit the economic potential of these technologies. The paper ends by outlining important policy issues that require new statistical efforts. Résumé L'OCDE offre aux gouvernements depuis plus de 20 ans un cadre de discussion sur les questions liées à la société de l'Information et propose des lignes directrices ainsi que des recommandations sur des sujets tels que la vie privée et l'informatique, la sécurité informatique, la cryptographie, la réforme réglementaire en matière de communications et, plus récemment, la protection des consommateurs en-ligne et la fiscalité en matière de commerce électronique. Jusqu'ici, ce travail a été plus ou moins accompli sans le bénéfice d'études statistiques approfondies. Cependant, à en juger des performances économiques d'un certain nombre de pays membres de l'OCDE au cours des années 90, il est évident que les problèmes auxquels est confrontée la société de l'Information ont un caractère de plus en plus économique,l'impact des technologies de l'information et des communications sur la productivité, les taux de croissance, l'inflation, le marché de l'emploi, etc.,et nécessitent des statistiques fiables. Le présent document explique comment les offices nationaux des statistiques ont contribué par leurs efforts à améliorer la situation en donnant aux chercheurs les moyens de mieux comprendre l'impact des technologies de l'information et des communications (TIC), notamment du commerce électronique, sur l'économie. Enfin, ce travail a abouti à un certain nombre de recommandations sur la meilleure façon pour les pouvoirs publics d'exploiter le potentiel économique de ces technologies. La dernière partie du document met en exergue des problèmes importants liés à la politique économique qui nécessitent de nouveaux efforts en matière de statistiques. [source] Jus Post Bellum: Just War Theory and the Principles of Just PeaceINTERNATIONAL STUDIES PERSPECTIVES, Issue 4 2006ROBERT E. WILLIAMS JR. What happens following a war is important to the moral judgments we make concerning warfare, just as the intentions going in and the means used are. There has, however, been inadequate attention paid to considerations of jus post bellum in the just war tradition. This essay seeks to contribute to recent efforts to develop jus post bellum principles by first noting some of the ways that jus ad bellum and jus in bello considerations serve to constrain what can legitimately be done after war. We argue, however, that the constraints grounded in traditional just war theory do not offer sufficient guidance for judging postwar behavior and that principles grounded in the concept of human rights are needed to complete our understanding of what constitutes a just war. A just peace exists when the human rights of those involved in the war, on both sides, are more secure than they were before the war. [source] Thiol oxidation of cell signaling proteins: Controlling an apoptotic equilibriumJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2004Janet V. Cross Abstract Studies of cell signal transduction have predominantly focused on regulation of protein function by phosphorylation. However, recent efforts have begun to uncover another layer of regulation mediated by direct oxidation of cysteine residues in signaling proteins. Typically induced during signaling responses accompanied by generation of reactive oxygen species, these thiol modifications have a variety of functional consequences for target proteins. Using specific signaling protein targets as examples, we discuss how thiol oxidation generally activates pro-apoptotic signaling pathways while inhibiting pathways that promote cell survival. We propose a model in which thiol oxidation acts to control the equilibrium between survival and apoptosis, fine tuning cellular responses that play a central role in the apoptotic decision-making process. We identify areas of focus for future work, including a better understanding of specificity in thiol oxidation events, and a critical need for approaches to examine these modifications under physiologically relevant signaling conditions. © 2004 Wiley-Liss, Inc. [source] Histological evolution of lentiginous melanoma: a report of five new casesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2007Tracy Davis Background:, The term lentiginous melanoma was recently used for atypical melanocytic proliferations sharing some histological features with lentigo maligna and associated with a protracted in situ stage before invasion. Lentiginous melanoma was characterized by predominantly single-cell lentiginous growth pattern with focal junctional nests and pagetoid spread, preservation of the dermoepidermal junction, limited cytological atypia, and lack of significant solar elastosis. We report five similar cases. Methods:, Histological review of routine sections with clinicopathological correlation. Results:, Three patients were male and two were female. The age at presentation ranged from 24 to 66 years. All lesions arose on the truck or proximal extremities. All five cases fulfilled histological criteria proposed for lentiginous melanoma. None of the lesions showed significant solar elastosis. One lesion was followed clinically and histologically for 16 years without intervening treatment. It had three local recurrences before culminating in invasive melanoma. Conclusions:, Our observations support recent efforts to distinguish lentiginous melanoma as a distinct clinicopathological entity. Lentiginous melanoma can remain in situ for a long time before invasion and may be considered an analogue of lentigo maligna occurring on non-severely sun-damaged skin. Familiarity with the histological features of this variant is important for its early recognition and treatment. [source] Human embryonic stem cells and liver diseases: From basic research to future clinical applicationJOURNAL OF DIGESTIVE DISEASES, Issue 1 2008Zheng WANG Human embryonic stem cells (hESC) provide access to the earliest stages of human development and because of their high proliferation capability, pluripotency and low immunogenicity may serve as a potential source of specialized cells for regenerative medicine. hESC-derived hepatocyte-like cells exhibit characteristic hepatocyte morphology, express hepatocyte markers and are capable of executing a range of hepatocyte functions. However, there are many challenges and obstacles to be overcome before the use of hESC and hESC-derived hepatocyte-like cells in clinical practice can be realized. Here, we highlight some of the recent efforts in this area, in hope of providing insights toward this complex yet important area of therapeutical modality for treating patients with liver disease. [source] Towards a rational development of anti-endotoxin agents: novel approaches to sequestration of bacterial endotoxins with small moleculesJOURNAL OF MOLECULAR RECOGNITION, Issue 6 2001Sunil A. David Abstract Endotoxins, or lipopolysaccharides (LPS), present on the surface of Gram-negative bacteria, play a key role in the pathogenesis of septic shock, a common clinical problem and a leading cause of mortality in critically ill patients, for which no specific therapeutic modalities are available at the present time. The toxic moiety of LPS is a glycolipid called ,lipid A', which is composed of a bisphosphorylated diglucosamine backbone bearing up to seven acyl chains in ester and amide linkages. Lipid A is structurally highly conserved in Gram-negative bacteria, and is therefore an attractive target for developing anti-endotoxin molecules designed to sequester, and thereby neutralize, the deleterious effects of endotoxins. The anionic and amphipathic nature of lipid A enables the interaction of a wide variety of cationic amphiphiles with the toxin. This review describes the systematic evaluation of several structural classes of cationic amphiphiles, both peptides and non-peptidic small molecules, in the broader context of recent efforts aimed at developing novel anti-endotoxin strategies. The derivation of a pharmacophore for LPS recognition has led to the identification of novel, nontoxic, structurally simple small molecules, the lipopolyamines. The lipopolyamines bind and neutralize LPS in in vitro experiments as well as in animal models of endotoxicity, and thus present novel and exciting leads for rational, structure-based development of LPS-sequestering agents of potential clinical value. Copyright © 2001 John Wiley & Sons, Ltd. [source] Preferences for Perinatal Health Communication of Women in Rural TibetJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 1 2009Phuoc V. Le ABSTRACT Objective: To describe the most acceptable methods for educating women in Medrogongkar County, Tibet, about healthy pregnancy and safe motherhood. Design: Focus group discussions with key informants were used to develop a quantitative, orally administered random sample survey. Setting: Thirty-two randomly selected villages in Medrogongkar County. Participants: One hundred and forty-eight multigravida over the age of 18 living in Medrogongkar County. Results: Most participants reported receiving pregnancy-related information either from family members (n=85, 57.4%) or from community health workers (n=81, 54.7%), while very few reported group teaching or radio/television/videos as sources. When asked what modalities of health communication are most effective for them, participants preferred discussions with family members (n=59, 39.8%), specifically their mothers (n=34, 23.0%). Community health worker teaching (n=15, 10.1%) or group teaching (n=7, 4.7%) were reported as less effective. Conclusions: Despite recent efforts in Tibet to use group teaching, television/radio programs, and health professionals visiting patients' homes as health communication modalities, participants preferred to learn pregnancy-related health messages from their close family, especially their mothers. Future health communication interventions in rural Tibet and similar communities should consider targeting close family members as well as pregnant women to maximize acceptability of advice on healthy pregnancy and delivery. [source] Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticlesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2001Julián F. Hillyer Abstract The gastrointestinal uptake of micro- and nanoparticles has been the subject of recent efforts to develop effective carriers that enhance the oral uptake of drugs and vaccines. Here, we used correlative instrumental neutron activation analysis and electron microscopy to quantitatively and qualitatively study the gastrointestinal uptake and subsequent tissue/organ distribution of 4, 10, 28, and 58 nm diameter metallic colloidal gold particles following oral administration to mice. In our quantitative studies we found that colloidal gold uptake is dependent on particle size: smaller particles cross the gastrointestinal tract more readily. Electron microscopic studies showed that particle uptake occurred in the small intestine by persorption through single, degrading enterocytes in the process of being extruded from a villus. To our knowledge this is the first report, at the ultrastructural level, of gastrointestinal uptake of particulates by persorption through holes created by extruding enterocytes. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1927,1936, 2001 [source] Demographic Issues in Longevity Risk AnalysisJOURNAL OF RISK AND INSURANCE, Issue 4 2006Eric Stallard Fundamental to the modeling of longevity risk is the specification of the assumptions used in demographic forecasting models that are designed to project past experience into future years, with or without modifications based on expert opinion about influential factors not represented in the historical data. Stochastic forecasts are required to explicitly quantify the uncertainty of forecasted cohort survival functions, including uncertainty due to process variance, parameter errors, and model misspecification errors. Current applications typically ignore the latter two sources although the potential impact of model misspecification errors is substantial. Such errors arise from a lack of understanding of the nature and causes of historical changes in longevity and the implications of these factors for the future. This article reviews the literature on the nature and causes of historical changes in longevity and recent efforts at deterministic and stochastic forecasting based on these data. The review reveals that plausible alternative sets of forecasting assumptions have been derived from the same sets of historical data, implying that further methodological development will be needed to integrate the various assumptions into a single coherent forecasting model. Illustrative calculations based on existing forecasts indicate that the ranges of uncertainty for older cohorts' survival functions will be at a manageable level. Uncertainty ranges for younger cohorts will be larger and the need for greater precision will likely motivate further model development. [source] | |||||||||||||||||||||||||||||||