			Home About us Contact

Major Focus (major + focus)

Distribution by Scientific Domains

Medical Sciences	39%
Life Sciences	30%
Humanities and Social Sciences	12%
Business, Economics, Finance and Accounting	9%
Chemistry	6%

Distribution within Medical Sciences

Immunology	15%

Selected Abstracts

Reciprocal relationships and potential feedbacks between biodiversity and disturbance

ECOLOGY LETTERS, Issue 9 2007
A. Randall Hughes
Abstract Two major foci of ecological research involve reciprocal views of the relationship between biodiversity and disturbance: disturbance determines community diversity or diversity determines realized disturbance severity. Here, we present an initial attempt to synthesize these two approaches in order to understand whether feedbacks occur, and what their effects on patterns of diversity might be. Our review of published experiments shows that (i) disturbance severity can be both a cause and a consequence of local diversity in a wide range of ecosystems and (ii) shapes of the unidirectional relationships between diversity and disturbance can be quite variable. To explore how feedbacks between diversity and disturbance might operate to alter expected patterns of diversity in nature, we develop and then evaluate a conceptual model that decomposes the relationships into component parts, considering sequentially the effect of diversity on disturbance severity, and the effect of realized disturbance on diversity loss, subsequent recruitment, and competitive exclusion. Our model suggests that feedbacks can increase mean values of richness, decrease variability, and alter the patterns of correlation between diversity and disturbance in nature. We close by offering ideas for future research to help fill gaps in our understanding of reciprocal relationships among ecological variables like diversity and disturbance. [source]

Collagenase-Assisted Fat Dissociation for Autologous Fat Transfer

DERMATOLOGIC SURGERY, Issue 10 2008
DAVID K. MOSCATELLO PHD
BACKGROUND The quality of fat for autologous transfer procedures has been a major focus of research in the past few years. The primary goal of these efforts is to improve the viability and longevity of the graft in human subjects. One possible factor in the permanence of theses transplants is the size of the adipose tissue grafts. OBJECTIVE This study evaluated the effects of collagenase digestion on the viability of human adipose tissue. MATERIALS AND METHODS Samples of fat were obtained from subjects undergoing tumescent liposuction. The tissue was digested in a variety of concentrations of collagenase using optimized methods of processing. The digested fat was also subjected to mock injections through small bore needles. RESULTS Eight subjects completed the study. The viability of the fat using the optimized methods of collagenase digestion was consistently higher than 79%. During the mock injection trials, the viability of fat was improved from approximately 17% to 84% by collagenase digestion. CONCLUSIONS Our results show increased viability of human adipose tissue when digested by collagenase. These techniques can be applied to human autologous lipoaugmentation procedures in an effort to improve longevity of the transplanted tissue. [source]

The renin,angiotensin system and the long-term complications of diabetes: pathophysiological and therapeutic considerations

DIABETIC MEDICINE, Issue 8 2003
R. E. Gilbert
Abstract The relationship between the renin,angiotensin system (RAS) and the progression of diabetic renal disease has been a major focus of investigation over the past 20 years. More recently, experimental and clinical studies have also suggested that the RAS may have a pathogenetic role at other sites of micro- and macrovascular injury in diabetes. Complementing major advances into the understanding of the local, as distinct from the systemic RAS, a number of large clinical trials have examined whether blockade of the RAS might provide protection from the long-term complications of diabetes, beyond that due to blood pressure reduction alone. While some controversy remains, these studies have, in general, suggested that angiotensin converting enzyme (ACE) inhibition and more recently, angiotensin receptor blockade reduce the development and progression of diabetic nephropathy, cardiovascular disease and possibly retinopathy. This review will focus on recent developments in our understanding of the tissue-based RAS and its role in end-organ injury in diabetes, the results of recent clinical trials and newer strategies for the pharmacological manipulation of the RAS. [source]

Coefficient shifts in geographical ecology: an empirical evaluation of spatial and non-spatial regression

ECOGRAPHY, Issue 2 2009
L. Mauricio Bini
A major focus of geographical ecology and macroecology is to understand the causes of spatially structured ecological patterns. However, achieving this understanding can be complicated when using multiple regression, because the relative importance of explanatory variables, as measured by regression coefficients, can shift depending on whether spatially explicit or non-spatial modeling is used. However, the extent to which coefficients may shift and why shifts occur are unclear. Here, we analyze the relationship between environmental predictors and the geographical distribution of species richness, body size, range size and abundance in 97 multi-factorial data sets. Our goal was to compare standardized partial regression coefficients of non-spatial ordinary least squares regressions (i.e. models fitted using ordinary least squares without taking autocorrelation into account; "OLS models" hereafter) and eight spatial methods to evaluate the frequency of coefficient shifts and identify characteristics of data that might predict when shifts are likely. We generated three metrics of coefficient shifts and eight characteristics of the data sets as predictors of shifts. Typical of ecological data, spatial autocorrelation in the residuals of OLS models was found in most data sets. The spatial models varied in the extent to which they minimized residual spatial autocorrelation. Patterns of coefficient shifts also varied among methods and datasets, although the magnitudes of shifts tended to be small in all cases. We were unable to identify strong predictors of shifts, including the levels of autocorrelation in either explanatory variables or model residuals. Thus, changes in coefficients between spatial and non-spatial methods depend on the method used and are largely idiosyncratic, making it difficult to predict when or why shifts occur. We conclude that the ecological importance of regression coefficients cannot be evaluated with confidence irrespective of whether spatially explicit modelling is used or not. Researchers may have little choice but to be more explicit about the uncertainty of models and more cautious in their interpretation. [source]

Pathogen safety of manufacturing processes for biological products: special emphasis on KOGENATE® Bayer

HAEMOPHILIA, Issue 2002
D. C. Lee
Summary., Manufacturers of human therapeutic proteins derived from biological sources continuously strive to improve the pathogen safety profiles of these products. Efforts to improve pathogen safety margins for these biological products are directed towards several areas within the manufacturing processes including: (a) sourcing and screening of raw materials (b) determining the potential for manufacturing processes to reduce pathogen titres, and (c) incorporating methods designed specifically to remove or inactivate contaminating pathogens. Methods that could potentially reduce pathogen titres are a major focus for many manufacturers. In general, these methods are grouped into two categories, pathogen clearance and pathogen inactivation. Assessments are performed on small-scale, laboratory simulations of the manufacturing process of interest that are spiked with a known amount of a selected pathogen. These studies provide estimates of the potential for a process step to remove or inactivate a particular pathogen. There are several pathogen clearance/inactivation methods that are inherent in manufacturing processes, however, some methods are intentionally incorporated into manufacturing for the sole purpose of reducing putative pathogen titres. Not only are well-known pathogens such as viruses targeted, but also suspected pathogens such as those associated with the transmissible spongiform encephalopathies (TSEs). The production processes for the isolation of several biological products, including recombinant KOGENATE® Bayer (Kogenate®FS), have been evaluated for the ability to reduce pathogen titres and/or have been designed to incorporate methods for reducing potential pathogen safety risks. Several processing steps with the potential to reduce pathogen titres have been identified. [source]

Migrants and Changing Urban Periphery: Social Relations, Cultural Diversity and the Public Space in Istanbul's New Neighbourhoods

INTERNATIONAL MIGRATION, Issue 3 2008
Sencer Ayata
This study examines the dynamics of socio-cultural change in a peripheral neighbourhood in Istanbul, an "edge city" that is ethnically mixed, culturally heterogeneous, socially differentiated and spatially multi-functional. One major focus in the study is the changing nature of social relations in traditional groups. Though kinship, hem,eri (place of origin) and neighbourhood solidarity is still crucial in the lives of the migrants, participation in these groups becomes more voluntary and the ties among members less obligatory. Secondly, the ethnic and religious groupings in the neighbourhood are not always exclusive, authoritarian and patriarchal communities. What generally appears as rigid communitarian fragmentation is often one of cultural diversity for the residents of the locality. The associational pluralism that exists in the neighbourhood enables people to claim multiple ethnic, religious, political and cultural identities. Thirdly, though they compare unfavourably with their middle class counterparts in the city, the new neighbourhoods provide greater opportunities and more public space for interaction among the members of the locality than for instance, the rural communities. The study also questions the often taken-for-granted image of a rigidly polarized city in view of empirical evidence that indicates the multiple and complex economic and political links between the new neighbourhoods and the broader urban society. Finally, isolation from middle class areas in the city does not necessarily lead to the exclusion of the whole peripheral urban population from urban life, urban institutions and urban culture. These become increasingly present in the new neighbourhoods and available for the majority of the residents. The main conclusion is that Istanbul contains a number of such edge cities, which have powerful integrating and urbanizing influences on individuals. Les migrants et l'évolution de la périphérie urbaine: relations sociales, diversité culturelle et espace public dans les nouveaux quartiers d'Istanbul La présente étude examine la dynamique des changements socioculturels dans un quartier de la périphérie d'Istanbul, une « ville-lisière » (edge city) caractérisée par sa mixité ethnique, son hétérogénéité culturelle, sa différenciation sociale et son espace multifonctionnel. L'un des principaux axes de la présente étude est la nature changeante des relations sociales au sein des groupes traditionnels. Premièrement, bien que la parenté, hem,eri (le lieu d'origine), et la solidarité des résidants des quartiers restent essentiels dans la vie des migrants, la participation à ces groupes devient plus volontaire et les liens entre ses membres sont moins contraints. Deuxièmement, les regroupements ethniques et religieux au sein des quartiers ne constituent pas toujours des communautés privées, autoritaires et patriarcales. Ce qui semble généralement être une fragmentation rigide en communautés est souvent une marque de la diversité culturelle pour les résidants de la localité. Le pluralisme des associations permet aux personnes de revendiquer différentes identités ethniques, religieuses, politiques et culturelles. Troisièmement, même s'ils ne peuvent soutenir la comparaison avec leurs équivalents urbains habités par la classe moyenne, ces nouveaux quartiers offrent davantage de possibilités et d'espace public pour les rencontres entre membres de la localité que les communautés rurales par exemple. L'étude remet aussi en question l'image que l'on a souvent d'une ville rigide et polarisée en faisant état des témoignages empiriques qui attestent de la complexité et de la multitude des liens économiques et politiques entre les nouveaux quartiers et la société urbaine au sens large. Enfin, être isolé des zones urbaines où habitent les classes moyennes n'entraîne pas nécessairement l'exclusion de l'ensemble de la population urbaine vivant en périphérie de la vie, des institutions et de la culture urbaines qui sont de plus en plus présentes dans les nouveaux quartiers et accessibles à la majorité des résidants. La conclusion principale est qu'Istanbul comporte un certain nombre de villes-lisières de ce genre, dont l'influence sur les habitants en matière d'intégration et d'urbanisation est très forte. Relaciones sociales, diversidad cultural y espacio público en los nuevos vecindarios de Estambul En este estudio se examina la dinámica del cambio sociocultural en los vecindarios periféricos de Estambul, una "ciudad suburbana"étnicamente mixta, culturalmente heterogénea, socialmente diferenciada y espacialmente multifuncional. Uno de los principales centros de atención de este estudio es la naturaleza cambiante de las relaciones sociales en los grupos tradicionales. Si bien la buena voluntad, el hem,eri (lugar de origen) y la solidaridad de los vecinos siguen siendo fundamentales en la vida de los migrantes, la participación en estos grupos se convierte en una cuestión de carácter voluntario y los vínculos entre los mismos no son obligatorios. En segundo lugar, las agrupaciones étnicas y religiosas en el vecindario no siempre son comunidades exclusivas, autoritarias o patriarcales. Lo que, generalmente, parece ser una fragmentación comunitaria rígida es más bien una diversidad cultural de los residentes de la localidad. El pluralismo asociativo que existe en el vecindario permite a las personas preservar diversas identidades étnicas, religiosas, políticas y culturales. En tercer lugar, si bien salen desfavorecidos en la comparación con sus equivalentes de la clase media en la ciudad, los nuevos vecindarios proveen mayores oportunidades y espacio público para la interacción de sus miembros de la localidad que, por ejemplo, las comunidades rurales. Este estudio también cuestiona la imagen a priori de una ciudad rígidamente polarizada ya que hay pruebas que indican los múltiples y complexos vínculos económicos y políticos existentes entre los nuevos vecindarios y la sociedad urbana amplia. Finalmente, el aislamiento de zonas de la clase media en la ciudad no conduce necesariamente a su exclusión de la vida, instituciones y cultura urbanas. Estas están omnipresentes en los nuevos vecindarios y disponibles para la mayoría de sus residentes. La principal conclusión de este artículo es que Estambul contiene una serie de estas ciudades periféricas, que tienen poderosas influencias integradoras y urbanizadoras en las personas. [source]

Trade Creation and Diversion Effects of Preferential Trade Associations on Agricultural and Food Trade

JOURNAL OF AGRICULTURAL ECONOMICS, Issue 1 2009
David Lambert
Q17; Q18; F13 Abstract Agricultural market distortions remain a major focus of contention in world trade negotiations. Estimates of the effects of liberalising current agricultural trade restrictions indicate an approximately $385 billion increase in global welfare, with the disproportionate share of the benefit being enjoyed by developing countries. In response to difficulties in adopting agricultural trade reforms, individual groups of countries have formed multiple bilateral and regional preferential trade agreements (PTA) to enhance trade among members. Few sectoral analyses exist of the effects on agricultural and food product trade of PTAs. This research uses a gravity model to isolate the effects of various PTAs on both intra- and extra-bloc agricultural and food product trade for three time periods: 1995, 2000 and 2004. Findings strongly support PTA benefits in terms of increased intra-bloc trade in both sectors. The findings also generally support trade creation in agricultural products. PTA membership was also associated with food trade creation in most cases, although diversion was observed for several associations composed primarily of developing countries. [source]

Caloric Restriction and Caloric Restriction Mimetics: Current Status and Promise for the Future

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9s 2005
George S. Roth PhD
Dietary caloric restriction is the most reproducible means of extending longevity and maintaining health and vitality. It has been shown to be relevant to a wide rage of species, including primates. Examination of key markers of the calorically restricted phenotype, such as plasma insulin, dehydroepiandrosterone sulfate, and body temperature, suggest that they may predict longevity in humans as well. However, most people would be unwilling or unable to adopt the 30% to 40% reduction in food intake necessary to achieve optimal health and longevity benefits. For this reason, a number of laboratories are pursuing caloric restriction mimetics: ways to achieve the benefits of restriction without eating less. This approach will undoubtedly remain a major focus of biogerontolgy for the foreseeable future. [source]

Calorie restriction mimetics: an emerging research field

AGING CELL, Issue 2 2006
Donald K. Ingram
Summary When considering all possible aging interventions evaluated to date, it is clear that calorie restriction (CR) remains the most robust. Studies in numerous species have demonstrated that reduction of calories 30,50% below ad libitum levels of a nutritious diet can increase lifespan, reduce the incidence and delay the onset of age-related diseases, improve stress resistance, and decelerate functional decline. A current major focus of this research area is whether this nutritional intervention is relevant to human aging. Evidence emerging from studies in rhesus monkeys suggests that their response to CR parallels that observed in rodents. To assess CR effects in humans, clinical trials have been initiated. However, even if results from these studies could eventually substantiate CR as an effective pro-longevity strategy for humans, the utility of this intervention would be hampered because of the degree and length of restriction required. As an alternative strategy, new research has focused on the development of ,CR mimetics'. The objective of this strategy is to identify compounds that mimic CR effects by targeting metabolic and stress response pathways affected by CR, but without actually restricting caloric intake. For example, drugs that inhibit glycolysis (2-deoxyglucose), enhance insulin action (metformin), or affect stress signaling pathways (resveratrol), are being assessed as CR mimetics (CRM). Promising results have emerged from initial studies regarding physiological responses which resemble those observed in CR (e.g. reduced body temperature and plasma insulin) as well as protection against neurotoxicity (e.g. enhanced dopamine action and up-regulated neurotrophic factors). Ultimately, lifespan analyses in addition to expanded toxicity studies must be accomplished to fully assess the potential of any CRM. Nonetheless, this strategy clearly offers a very promising and expanding research endeavor. [source]

Multinational Firm Knowledge, Use of Expatriates, and Foreign Subsidiary Performance

JOURNAL OF MANAGEMENT STUDIES, Issue 1 2010
Yulin Fang
abstract The impact of knowledge transfer on foreign subsidiary performance has been a major focus of research on knowledge management in multinational enterprises (MNEs). By integrating the knowledge-based view and the expatriation literature, this study examines the relationship between a multinational firm's knowledge (i.e. marketing and technological knowledge), its use of expatriates, and the performance of its foreign subsidiaries. We conceptualize that expatriates play a contingent role in facilitating the transfer and redeployment of a parent firm's knowledge to its subsidiary, depending on the location specificity of the organizational knowledge being transferred and the time of transfer. Our analysis of 1660 foreign subsidiaries of Japanese firms over a 15-year period indicates that the number of expatriates relative to the total number of subsidiary employees (1) strengthened the effect of a parent firm's technological knowledge (with low location specificity) on subsidiary performance in the short term, but (2) weakened the impact of the parent firm's marketing knowledge (with high location specificity) on subsidiary performance in the long term. We also found that the expatriates' influence on knowledge transfer eventually disappeared. The implications for knowledge transfer research and the expatriate management literature are discussed. [source]

The roles of NADPH oxidase and phospholipases A2 in oxidative and inflammatory responses in neurodegenerative diseases

JOURNAL OF NEUROCHEMISTRY, Issue 1 2007
Grace Y. Sun
Abstract Reactive oxygen species (ROS) are produced in mammalian cells through enzymic and non-enzymic mechanisms. Although some ROS production pathways are needed for specific physiological functions, excessive production is detrimental and is regarded as the basis of numerous neurodegenerative diseases. Among enzymes producing superoxide anions, NADPH oxidase is widespread in mammalian cells and is an important source of ROS in mediating physiological and pathological processes in the cardiovascular and the CNS. ROS production is linked to the alteration of intracellular calcium homeostasis, activation of Ca2+ -dependent enzymes, alteration of cytoskeletal proteins, and degradation of membrane glycerophospholipids. There is evolving evidence that ROS produced by NADPH oxidase regulate neuronal functions and degrade membrane phospholipids through activation of phospholipases A2 (PLA2). This review is intended to cover recent studies describing ROS generation from NADPH oxidase in the CNS and its downstream activation of PLA2, namely, the group IV cytosolic cPLA2 and the group II secretory sPLA2. A major focus is to elaborate the dual role of NADPH oxidase and PLA2 in mediating the oxidative and inflammatory responses in neurodegenerative diseases, including cerebral ischemia and Alzheimer's disease. Elucidation of the signaling pathways linking NADPH oxidase with the multiple forms of PLA2 will be important in understanding the oxidative and degradative mechanisms that underline neuronal damage and glial activation and will facilitate development of therapeutic intervention for prevention and treatment of these and other neurodegenerative diseases. [source]

Chronic and High Alcohol Consumption Has a Negative Impact on Sleep and Sleep-Associated Consolidation of Declarative Memory

ALCOHOLISM, Issue 5 2009
Klaus Junghanns
Background., The importance of sleep for memory consolidation has become a major focus of research. While it is known that abstaining alcohol-dependent patients often have sleep disorders and that there is some cognitive impairment during early abstention a possible interaction of disturbed sleep with overnight memory consolidation has not been addressed in a study as yet. Methods., Twenty-four alcohol-dependent patients with a short abstention period (mean 21.9 ± 7.6 days) were compared with 12 patients with an abstention period of several months (115.7 ± 43.8 days). Groups did not differ with respect to daily alcohol consumption before treatment, duration of alcohol dependence, and age. Before sleep all patients learned a list of semantically associated word pairs and a face name association task to a fixed criterion (at least 60% of correct recall) and they performed a mirror tracing task. After a polysomnographically registered night the patients were tested for retention of the learned declarative material by cued recall and had to perform the mirror tracing task again. Results., The groups did not differ with respect to sleep parameters or sleep-associated memory consolidation. Across both groups the duration of alcohol dependence correlated negatively with the amount of non-REM sleep and recall in the face name association task correlated negatively with daily alcohol consumption before abstention. Among the longer-term abstainers the duration of abstention correlated with the amount of slow wave sleep. Conclusions., Our data support the hypothesis that chronic and high alcohol consumption negatively affects sleep and declarative memory consolidation during the first months of abstention. Between an abstention period of a few weeks and of several months no change in sleep parameters and nightly memory consolidation could be demonstrated, however. [source]

Mental health professionals' attitudes towards consumer participation in inpatient units

JOURNAL OF PSYCHIATRIC & MENTAL HEALTH NURSING, Issue 1 2008
T. V. MCCANN rmn rgn phd ma ba dipnurs (lond) rnt rcnt
Consumer participation has been a major focus in mental health services in recent years, but the attitudes of mental health professionals towards this initiative remain variable. The purpose of this study was to describe mental health professionals' attitudes towards mental health consumer participation in inpatient psychiatric units. The Consumer Participation and Consultant Questionnaire was used with a non-probability sample of 47 mental health professionals from two adult inpatient psychiatric units situated in a large Australian public general hospital. Ethics approval was obtained from a university and a hospital ethics committee. Data were analysed using spss, Version 12. Overall, respondents had favourable attitudes towards consumer participation in management, care and treatment, and mental health planning. They were less supportive about matters that directly or indirectly related to their spheres of responsibility. The type of unit that the respondents worked in was not a factor in their beliefs about consumer participation. Recommendations are made about the development of guidelines for consumer participation in inpatient units, the educational preparation of mental health clinicians, and the need for mental health professionals to reflect on, and discuss their own beliefs and practices about, consumer participation. [source]

Secular trend in medical education regarding infectious disease

MEDICAL EDUCATION, Issue 10 2003
Kai Ming Chow
Objective ,The paradigm of global medical health has been re-characterised by a shift in its major focus from infectious disease to chronic illness. Opinions vary as to the declining emphasis on infectious disease. This paper provides clinicians with an understanding of a secular trend in medical education regarding the topic of infectious diseases over a period of 26 years. Methods ,A survey was carried out to evaluate coverage of infectious disease topics within recent general medicine textbooks and journals. Results ,The percentage of content dedicated to infectious disease has remained static in 2 major medical textbooks, whereas a trend towards decreasing coverage was shown in 4 major medical journals. Of 901 original articles published in 2000, 16·4% covered certain aspects of infectious disease, as compared with 20·9% of 790 articles published in 1985. Increasing rates of infectious disease mortality in developing countries were not consistently matched with the trend in coverage of infectious disease topics in either medical textbooks or journals. Conclusions ,Our data demonstrate that coverage of infectious disease topics in publications issued in developed countries was more indicative of global trends in disease mortality rather than those of developing countries. Medical education and knowledge, which are usually delivered by the rich nations where influential medical textbooks and journals are published, place less emphasis on infectious disease relative to the burden infectious disease places on the developing world. [source]

Using finite element method to calculate capacitance, inductance, characteristic impedance of open microstrip lines

MICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 3 2008
Sarhan M. Musa
Abstract Microstrip transmission lines have received more interest and attention in microwave integrated circuit design. Analysis and electrical characterization of single and coupled microstrip lines have been a major focus for researchers in integrated circuit technology. In this article, we will illustrate modeling of the capacitance, inductance, and characteristic impedance of quasi-TEM for open microstrip lines using finite element method with COMSOL multiphysics package. In this work, we determine the capacitance per unit length, inductance per unit length, and characteristic impedance of open microstrip lines (single-strip, double strip, and three-strip). We compare our results with those obtained by other methods and found them to be in agreement. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 611,614, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23164 [source]

How to build a fungal fruit body: from uniform cells to specialized tissue

MOLECULAR MICROBIOLOGY, Issue 4 2007
Silke Busch
Summary It is a challenge in biology to explore the molecular and cellular mechanisms necessary to form a complex three-dimensional structure composed of different cell types. Interesting models to study the underlying processes are fungi that can transform their wire-like hyphal filaments into complex and sometimes container-like fruit bodies. In the past, the role of developmental triggers and transcription factors was a major focus of research on fungal model organisms. In this issue of Molecular Microbiology, Nowrousian and collaborators report that fruit body development of the model organism Sordaria macrospora includes a novel player, a specific membrane protein of the endoplasmic reticulum that is not required for vegetative growth. This finding represents an important step towards connecting regulation of development with the co-ordinated changes in cellular compartments. [source]

Reduced-intensity allogeneic hematopoietic cell transplantation: Graft versus tumor effects with decreased toxicity

PEDIATRIC TRANSPLANTATION, Issue 3 2003
Jennifer E. Schwartz
Abstract: The potentially curative role of allogeneic hematopoietic cell transplantation (HCT) in neoplastic and non-neoplastic diseases is offset by the substantial risks of morbidity and mortality from complications of the intensive myeloablative and immunosuppressive preparative regimen. These regimen-related toxicities have restricted allogeneic HCT to young, otherwise healthy individuals without comorbid diseases. Pediatric patients undergoing conventional allogeneic HCT have lower procedure-related mortality but are at risk for non-fatal late effects of the high-dose pretransplant chemoradiotherapy, such as growth retardation, sterility and other endocrine dysfunction. Evaluation of reduced-intensity preparative regimens is the major focus of current clinical research in allogeneic HCT. Reduced-intensity HCT (RI-HCT) relies on the use of immunosuppressive but non-myeloablative agents that allow engraftment of donor cells, which provide adoptive allogeneic cellular immunotherapy and graft versus tumor (GVT) effects, with decreased regimen-related toxicities. Although the experience with RI-HCT in pediatric patients is very limited at this time, results in adults indicate that attenuated-dose preparative regimens allow older patients and those with organ dysfunction to undergo successful allogeneic HCT with acceptable morbidity and mortality. In adults, the potency of the allogeneic GVT effect varies among neoplastic diseases, with better results observed in patients with indolent hematological malignancies or renal cell carcinoma. The effectiveness of RI-HCT as treatment for children with hemoglobinopathies, chronic granulomatous disease and cellular immunodeficiencies is encouraging, and the role of reduced-intensity preparative regimens for allogeneic HCT in pediatric malignancies is under investigation. [source]

Balancing the Need to Develop Coastal Areas with the Desire for an Ecologically Functioning Coastal Environment: Is Net Ecosystem Improvement Possible?

RESTORATION ECOLOGY, Issue 1 2005
R.M. Thom
Abstract The global human population is growing exponentially, close to a majority lives and works near the coast, and coastal commerce and development are critical to the economies of many nations. Hence, coastal areas will continue to be a major focus of development and economic activity. People desire the economic advantages provided by coastal development along with the fisheries and social commodities supported by estuarine and coastal ecosystems. Because of these facts, we view the challenge of balancing coastal development with enhancing nearshore marine and estuarine ecosystems (i.e., net ecosystem improvement) as the top priority for coastal researchers in this century. Our restoration research in Pacific Northwest estuaries and participation in nearshore project design and impact mitigation has largely dealt with these competing goals. To this end, we have applied conceptual models, comprehensive assessment methods, and principles of restoration ecology, conservation biology, and adaptive management to incorporate science into decisions about uses of estuarine systems. Case studies of Bainbridge Island and the Columbia River demonstrate the use of objective, defensible methods to prioritize tidally influenced shorelines and habitats (i.e., riparian forests, marshes, unvegetated flats, rocky shores, seagrass meadows, kelp forests) for preservation, conservation, and restoration. Case studies of Clinton, Washington, and Port Townsend, Washington, demonstrate the incorporation of an ecological perspective and technological solutions into design of overwater structures to minimize impacts on nearshore ecosystems. Adaptive management has allowed coastal development and restoration uncertainties to be better evaluated, with the information used to improve management decisions. Although unproven on a large scale, we think these kinds of methods can contribute to the net improvement of already degraded ecosystems. The ingredients include applied science to understand the issues, education, incentives, empirical data, cumulative impact analysis, and an effective adaptive management program. Because the option of net ecosystem improvement is often more costly than alternatives such as no net loss, commitment by the local or regional community to this approach is essential. [source]

The Separation of Powers, Court Curbing, and Judicial Legitimacy

AMERICAN JOURNAL OF POLITICAL SCIENCE, Issue 4 2009
Tom S. Clark
A major focus of judicial politics research has been the extent to which ideological divergence between the Court and Congress can explain variation in Supreme Court decision making. However, conflicting theoretical and empirical findings have given rise to a significant discrepancy in the scholarship. Building on evidence from interviews with Supreme Court justices and former law clerks, I develop a formal model of judicial-congressional relations that incorporates judicial preferences for institutional legitimacy and the role of public opinion in congressional hostility towards the Supreme Court. An original dataset identifying all Court-curbing legislation proposed between 1877 and 2006 is then used to assess the influence of congressional hostility on the Court's use of judicial review. The evidence indicates that public discontent with the Court, as mediated through congressional hostility, creates an incentive for the Court to exercise self-restraint. When Congress is hostile, the Court uses judicial review to invalidate Acts of Congress less frequently than when Congress is not hostile towards the Court. [source]

Symposium on Social Capital: Introduction

THE ECONOMIC JOURNAL, Issue 483 2002
Steven N. Durlauf
This symposium contains three papers that discuss aspects of social capital. Social capital has become a major focus of research in many social sciences. Its increased prominence in economics reflects a general increase in interest in questions that have traditionally been deemed sociological. Regardless of one's opinion of social capital per se, this broadening of questions addressed within economics has been very salutary. [source]

Antigenic Variation in Ciliates: Antigen Structure, Function, Expression,

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 1 2007
MARTIN C. SIMON
ABSTRACT. In the past decades, the major focus of antigen variation research has been on parasitic protists. However, antigenic variation occurs also in free-living protists. The antigenic systems of the ciliates Paramecium and Tetrahymena have been studied for more than 100 yr. In spite of different life strategies and distant phylogenetic relationships of free-living ciliates and parasitic protists, their antigenic systems have features in common, such as the presence of repeated protein motifs and multigene families. The function of variable surface antigens in free-living ciliates is still unknown. Up to now no detailed monitoring of antigen expression in free-living ciliates in natural habitats has been performed. Unlike stochastic switching in parasites, antigen expression in ciliates can be directed, e.g. by temperature, which holds great advantages for research on the expression mechanism. Regulated expression of surface antigens occurs in an exclusive way and the responsible mechanism is complex, involving both transcriptional and post-transcriptional features. The involvement of homology-dependent effects has been proposed several times but has not been proved yet. [source]

Phenotypic Expression of Recurrent Disease After Liver Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010
J. G. O'Grady
Recurrence of the primary disease has become a major focus for transplant hepatologists both when investigating graft dysfunction and when tailoring immunosuppression to maximize graft survival. However, disease recurrence varies in penetrance, can be predictable or random, and does not always conform to the expected pattern of disease. The cholestatic hepatitis syndromes associated with hepatitis B and C are the most dramatic examples of phenotypic change. Being on immunosuppressive drugs may intensify the progression of infectious and malignant diseases, but this effect is not predictable. A significant minority of patients with each of the autoimmune diseases, counter-intuitively, get recurrent disease despite immunosuppression of a potency that is adequate to prevent rejection of the liver graft. Disease patterns emerge after liver transplantation for cryptogenic cirrhosis that shed light on the cause of the native liver disease, for example, nonalcohol-related fatty liver disease and autoimmune hepatitis. The phenotypic expression of disease recurrence can be modified by specific drugs used for immunosuppression and by HLA-antigen matching profiles. Understanding and modifying the phenotypic expression of recurrent disease after liver transplantation is a fertile area for research and continued refinement of clinical care. [source]

Winners and losers in human-made habitats: interspecific competition outcomes in two Neotropical vultures

ANIMAL CONSERVATION, Issue 4 2010
M. Carrete
Abstract Understanding the factors underlying species coexistence is a major focus in community ecology. When dealing with competition between native and exotic species, the competitive exclusion of the ,weaker' species can have consequences for biodiversity conservation. We examined interspecific interactions during foraging between black vultures Coragyps atratus and Andean condors Vultur gryphus in Southern Argentina. Previous studies suggest facilitatory interactions between them. However, in most parts of their distribution ranges, these species did not coexist until recently, when black vultures expanded their geographic range following human development. Thus, facilitatory processes or segregation patterns could not be fine-tuned enough to allow their coexistence. Our hypothesis is that black vultures and Andean condors compete for food resources, and that this competitive scenario can change depending on local species abundances and habitat humanization. We experimentally placed sheep carcasses in two habitats differing in degrees of humanization to study the foraging patterns in these species. Both species exploited carcasses with similar temporal patterns. However, the first to arrive and the dominant species were different in both habitats, according to their abundances. Although black vultures do not completely prevent the arrival of Andean condors to carcasses, they represent serious obstacles for feeding. Thus, while dominance hierarchy at carcasses could be related to body size, carcass consumption was determined by species abundance. Our results support the hypothesis that the expansion of a ,winning' species may trigger interspecific competition with other ,loser' species, with negative responses towards human activities when they became abundant. Although the results are not conclusive, invasion and extinction processes could be occurring and they can have serious consequences for the diversity (i.e. richness and evenness) of the New World scavenger guilds. [source]

Co-ordinating innate and adaptive immunity to viral infection: mobility is the key

APMIS, Issue 5-6 2009
JEANETTE ERBO CHRISTENSEN
The host counters a viral infection through a complex response made up of components belonging to both the innate and the adaptive immune system. In this report, we review the mechanisms underlying this response, how it is induced and how it is co-ordinated. As cell,cell communication represents the very essence of immune system physiology, a key to a rapid, efficient and optimally regulated immune response is the ability of the involved cells to rapidly shift between a stationary and a mobile state, combined with stringent regulation of cell migration during the mobile state. Through the co-ordinated recruitment of different cell types intended to work in concert, cellular co-operation is optimized particularly under conditions that may involve rare cells. Consequently, a major focus is placed on presenting an overview of the co-operative events and the associated cell migration, which is essential in mounting an efficient host response and co-ordinating innate and adaptive immunity during a primary viral infection. [source]

Bioethics: Power and Injustice: Iab Presidential Address

BIOETHICS, Issue 5-6 2003
Solomon R. Benatar
ABSTRACT A major focus within the modern bioethics debate has been on reshaping power relationships within the doctor,patient relationship. Empowerment of the vulnerable has been achieved through an emphasis on human rights and respect for individual dignity. However, power imbalances remain pervasive within healthcare. To a considerable extent this relates to insufficient attention to social injustice. Such power imbalances together with the development of new forms of power, for example through new genetic biotechnology, raise the spectre of increasing social injustice. Attention will be drawn to the need to extend the bioethics debate to include ethical considerations regarding public health. Changes in political philosophy will also be required to reshape international power relations and improve population health. [source]

Flower visitors and pollination in the Oriental (Indomalayan) Region

BIOLOGICAL REVIEWS, Issue 3 2004
Richard T. Corlett
ABSTRACT Current knowledge of flower visitors and pollination in the Oriental Region is summarised. Much less is known about pollination than seed dispersal and the coverage of habitats and taxa in the region is very uneven. The available evidence suggests that pollination in lowland forests is dominated by highly social bees (mainly Trigona and Apis species), with beetles probably the next most important group, followed by other bees and flies. In comparison with the better-studied Neotropics, large solitary bees, moths, Lepidoptera and vertebrates are relatively less important. These differences are greatest in the canopy of the lowland dipterocarp forests of Southeast Asia, where they probably reflect the unique temporal pattern of floral resource availability resulting from,general flowering'at supra-annual intervals. Apis bees (but not Trigona species) are also important in most montane, subtropical and non-forest habitats. Apart from the figs (Ficus spp.), there are few well-documented examples of plant species visited by a single potential pollinator and most plant-pollinator relationships in the region appear to be relatively generalised. The small sizes of most pollinators and the absence of direct human exploitation probably make pollination mutualisms less vulnerable to failure as a result of human impacts than dispersal mutualisms, but more subtle impacts, as a result of altered gene flows, are likely to be widespread. On current evidence, pollination systems in the Oriental Region do not require any specific conservation action, but this review reinforces arguments for making the preservation (or restoration) of habitat connectivity the major focus of Oriental conservation. [source]

Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2010
Adam L. VanWert
Abstract Our understanding of the mechanisms behind inter- and intra-patient variability in drug response is inadequate. Advances in the cytochrome P450 drug metabolizing enzyme field have been remarkable, but those in the drug transporter field have trailed behind. Currently, however, interest in carrier-mediated disposition of pharmacotherapeutics is on a substantial uprise. This is exemplified by the 2006 FDA guidance statement directed to the pharmaceutical industry. The guidance recommended that industry ascertain whether novel drug entities interact with transporters. This suggestion likely stems from the observation that several novel cloned transporters contribute significantly to the disposition of various approved drugs. Many drugs bear anionic functional groups, and thus interact with organic anion transporters (OATs). Collectively, these transporters are nearly ubiquitously expressed in barrier epithelia. Moreover, several reports indicate that OATs are subject to diverse forms of regulation, much like drug metabolizing enzymes and receptors. Thus, critical to furthering our understanding of patient- and condition-specific responses to pharmacotherapy is the complete characterization of OAT interactions with drugs and regulatory factors. This review provides the reader with a comprehensive account of the function and substrate profile of cloned OATs. In addition, a major focus of this review is on the regulation of OATs including the impact of transcriptional and epigenetic factors, phosphorylation, hormones and gender. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Toward understanding the inactivation mechanism of monooxygenase P450 BM-3 by organic cosolvents: A molecular dynamics simulation study

BIOPOLYMERS, Issue 5 2006
Danilo Roccatano
Abstract Cytochrome P450 BM-3 from Bacillus megaterium is an extensively studied enzyme for industrial applications. A major focus of current protein engineering research is directed to improving the catalytic performance of P450 BM-3 toward nonnatural substrates of industrial importance in the presence of organic solvents or cosolvents. For the latter reason, it is important to study the effect of organic cosolvent molecules on the structure and dynamics of the enzyme, in particular, the effect of cosolvent molecules on the active site's structure and dynamics. In this paper, we have studied, using molecular dynamics (MD) simulations, the F87A mutant of P450 BM-3 in the presence of DMSO as cosolvent, to understand the role of the F87A substitution for its catalytic activity. This mutant exhibits an altered regioselectivity and substrate specificity compared with wild-type; however, it has lower tolerance toward DMSO. The simulation results offer an explanation for the DMSO sensitivity of the F87A mutant. Our simulation results show that the F87 side chain prevents the disturbance of the water molecule bound to the heme iron by DMSO molecules. The absence of the phenyl ring in F87A mutant promotes interactions of the DMSO molecule with the heme iron resulting in water displacement by DMSO at the catalytic heme center. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 467,476, 2006 This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source]

Proteases in pathogenesis and plant defence

CELLULAR MICROBIOLOGY, Issue 10 2004
Yiji Xia
Summary Plant pathogens deliver a variety of virulence factors to host cells to suppress basal defence responses and create suitable environments for their propagation. Plants have in turn evolved disease resistance genes whose products detect the virulence factors as a signal of invasion and activate effective defence responses. Understanding how a virulence effector contributes to virulence on susceptible hosts but becomes an avirulence factor that triggers defence responses on resistance hosts has been a major focus in plant research. Recent studies have shown that a growing list of pathogen-encoded effectors functions as proteases that are secreted into plant cells to modify host proteins. In addition, several plant proteases have been found to function in activation of the defence mechanism. These findings reveal that post-translational modification of host proteins through proteolytic processing is a widely used mechanism in regulating the plant defence response. [source]

Are MAP Kinases Drug Targets?

CHEMMEDCHEM, Issue 8 2007
but Difficult Ones
Abstract Pharmaceutical companies are facing an increasing interest in new target identification and validation. In particular, extensive efforts are being made in the field of protein kinase inhibitors research and development, and the past ten years of effort in this field have altered our perception of the potential of kinases as drug targets. Therefore, in the drug discovery process, the selection of relevant, susceptible protein kinase targets combined with searches for leads and candidates have become a crucial approach. The success of recent launches of protein kinase inhibitors (Gleevec, Imatinib, Sutent, Iressa, Nexavar, Sprycel) gave another push to this field. Numerous other kinase inhibitors are currently undergoing clinical trials or clinical development. Some questions are nevertheless unanswered, mostly related to the great number of known kinases in the human genome, to their similarity with each other, to the existence of functionally redundant kinases for specific pathways, and also because the connection between particular pathways and diseases is not always clear. The review is leading the reader through a panoramic view of protein kinase inhibition with a major focus on MAPK, successful examples and clinical candidates. [source]