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Selected AbstractsEndothelin receptor selectivity in chronic kidney disease: rationale and review of recent evidenceEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2009W. Neuhofer Abstract Endothelin (ET) is a potent vasoconstrictory peptide with proinflammatory and profibrotic properties that exerts its biological effects through two pharmacologically distinct receptor subtypes, namely ETA and ETB. In addition to its substantial contribution to normal renal function, a large body of evidence suggests that derangement of the renal ET system is involved in the initiation and progression of chronic kidney disease (CKD) in diabetes, hypertension and glomerulonephritis. Thus, the use of ET receptor antagonists (ERAs) may offer potential novel treatment strategies in CKD. Recent literature on the role of the renal ET system in the healthy kidney was reviewed. In addition, an unbiased PubMed search was performed for studies published during the last 5 years that addressed the effects of ERAs in CKD. A particular objective was to extract information regarding whether selective or nonselective ERAs may have therapeutic potential in humans. ET-1 acts primarily as an autocrine or paracrine factor in the kidney. In normal physiology, ET-1 promotes diuresis and natriuresis by local production and action through ETB receptors in the renal medulla. In pathology, ET-1 mediates vasoconstriction, mesangial-cell proliferation, extracellular matrix production and inflammation, effects that are primarily conveyed by ETA receptors. Results obtained in animal models and in humans with the use of ERAs in CKD are encouraging; nevertheless, it is still under debate which receptor subtype should be targeted. According to most studies, selective inhibition of ETA receptors appears superior compared with nonselective ERAs because this approach does not interfere with the natriuretic, antihypertensive and ET clearance effects of ETB receptors. Although preliminary data in humans are promising, the potential role of ERAs in patients with CKD and the question of which receptor subtype should be targeted can only be clarified in randomized clinical trials. [source] An Approach to Fulfilling the Systems-based Practice Competency RequirementACADEMIC EMERGENCY MEDICINE, Issue 11 2002David Doezema MD The Accreditation Council for Graduate Medical Education (ACGME)-identified core competency of systems-based practice requires the demonstration of an awareness of the larger context and system of health care, and the ability to call on system resources to provide optimum care. This article describes an approach to teaching and fulfilling the requirement of this core competency in an emergency medicine residency. Beginning residents are oriented to community resources that are important to the larger context of care outside the emergency department. Each resident completes a community project during his or her residency. Readings and discussions concerning community-oriented medical care and the literature of research and injury prevention in emergency medicine precede the project development. Several projects are described in detail. Such projects help to teach not only awareness of the community resources of the greater context of medical practice outside the emergency department, but also how to use those resources. Projects could be a main component of a resident portfolio. This approach to teaching the core competency of systems-based practice is proposed as an innovative and substantial contribution toward satisfying the requirement of the core competency. [source] THE LOCUS OF EVOLUTION: EVO DEVO AND THE GENETICS OF ADAPTATIONEVOLUTION, Issue 5 2007Hopi E. Hoekstra An important tenet of evolutionary developmental biology ("evo devo") is that adaptive mutations affecting morphology are more likely to occur in the cis -regulatory regions than in the protein-coding regions of genes. This argument rests on two claims: (1) the modular nature of cis -regulatory elements largely frees them from deleterious pleiotropic effects, and (2) a growing body of empirical evidence appears to support the predominant role of gene regulatory change in adaptation, especially morphological adaptation. Here we discuss and critique these assertions. We first show that there is no theoretical or empirical basis for the evo devo contention that adaptations involving morphology evolve by genetic mechanisms different from those involving physiology and other traits. In addition, some forms of protein evolution can avoid the negative consequences of pleiotropy, most notably via gene duplication. In light of evo devo claims, we then examine the substantial data on the genetic basis of adaptation from both genome-wide surveys and single-locus studies. Genomic studies lend little support to the cis -regulatory theory: many of these have detected adaptation in protein-coding regions, including transcription factors, whereas few have examined regulatory regions. Turning to single-locus studies, we note that the most widely cited examples of adaptive cis -regulatory mutations focus on trait loss rather than gain, and none have yet pinpointed an evolved regulatory site. In contrast, there are many studies that have both identified structural mutations and functionally verified their contribution to adaptation and speciation. Neither the theoretical arguments nor the data from nature, then, support the claim for a predominance of cis -regulatory mutations in evolution. Although this claim may be true, it is at best premature. Adaptation and speciation probably proceed through a combination of cis -regulatory and structural mutations, with a substantial contribution of the latter. [source] Explaining the differences in income-related health inequalities across European countriesHEALTH ECONOMICS, Issue 7 2004Eddy van Doorslaer Abstract This paper provides new evidence on the sources of differences in the degree of income-related inequalities in self-assessed health in 13 European Union member states. It goes beyond earlier work by measuring health using an interval regression approach to compute concentration indices and by decomposing inequality into its determining factors. New and more comparable data were used, taken from the 1996 wave of the European Community Household Panel. Significant inequalities in health (utility) favouring the higher income groups emerge in all countries, but are particularly high in Portugal and , to a lesser extent , in the UK and in Denmark. By contrast, relatively low health inequality is observed in the Netherlands and Germany, and also in Italy, Belgium, Spain Austria and Ireland. There is a positive correlation with income inequality per se but the relationship is weaker than in previous research. Health inequality is not merely a reflection of income inequality. A decomposition analysis shows that the (partial) income elasticities of the explanatory variables are generally more important than their unequal distribution by income in explaining the cross-country differences in income-related health inequality. Especially the relative health and income position of non-working Europeans like the retired and disabled explains a great deal of ,excess inequality'. We also find a substantial contribution of regional health disparities to socio-economic inequalities, primarily in the Southern European countries. Copyright © 2004 John Wiley & Sons, Ltd. [source] IL23R haplotypes provide a large population attributable risk for Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2008Kent D. Taylor PhD Abstract Background: The IL-23 pathway plays a pivotal role in the development of chronic mucosal inflammation seen in the inflammatory bowel diseases. Multiple studies have now established the contribution of the interleukin 23 receptor gene (IL23R) to Crohn's disease (CD) risk in general and of the IL23R R381Q variant in particular. The aim of this work was to estimate the total contribution of this gene to CD risk test using a haplotype approach. Methods: In all, 763 CD subjects and 254 controls were genotyped for single nucleotide polymorphisms in the IL23R gene using Illumina and ABI methods. Haplotypes were assigned using PHASEv2 and tested for association with CD by chi-square and permutation. Results: Haplotypes with both increased and decreased risk for CD were observed in 2 of the 4 observed blocks (Block 2 H1: 55.4% control, 64% CD, P = 0.019; H2: 64.5% control, 54.4% CD, P = 0.006; Block 3 H1: 55.8% control, 64.4% CD, P = 0.013; H2: 47.0% control, 36.6% CD, P = 0.001). The population attributable risk for these haplotypes was substantially larger than that estimated for the IL23R R381Q variant (Block 2 H1 and block 3 H1 ,20%, compared with ,4% for Block 3 H6, containing the variant). Conclusions: These observations suggest that IL23R makes a substantial contribution to CD susceptibility, larger than that estimated from the population frequency of the R381Q variant. These observations also support the expectation that finding "hits" from genomewide association studies will be but an important chapter in the story of unraveling the genetic contribution to CD, rather than the final chapter that brings clarity to all the plot twists of a complicated story. (Inflamm Bowel Dis 2008) [source] The face and voice of volunteering: a suitable case for branding?INTERNATIONAL JOURNAL OF NONPROFIT & VOLUNTARY SECTOR MARKETING, Issue 2 2005Philippa Hankinson Volunteers make a substantial contribution to UK society but the level of volunteering has peaked and may, in part, be due to the poor ,image' of volunteering. Through qualitative research, this study explores the need to re-shape perceptions of volunteering and the extent to which this may be achieved through branding. Key findings suggest that although there is much consistency in perceptions about generic volunteering, perceptions of the different strands of volunteering, such as governance and campaigning, are different and may require individual development as sub-brands. It is argued that Volunteering England is best placed to lead a brand development programme, supported by managers of national and local bodies as well as volunteers to create a new visual identity and, importantly, key messages that will resonate with current and potential volunteers across different areas of activity. Copyright © 2005 John Wiley & Sons, Ltd. [source] The structural design of the bat wing web and its possible role in gas exchangeJOURNAL OF ANATOMY, Issue 6 2007Andrew N. Makanya Abstract The structure of the skin in the epauletted fruit bat (Epomophorus wahlbergi) wing and body trunk was studied with a view to understanding possible adaptations for gas metabolism and thermoregulation. In addition, gas exchange measurements were performed using a respirometer designed for the purpose. The body skin had an epidermis, a dermis with hair follicles and sweat glands and a fat-laden hypodermis. In contrast, the wing web skin was made up of a thin bilayered epidermis separated by a connective tissue core with collagen and elastic fibres and was devoid of hair follicles and sweat glands. The wings spanned 18,24 cm each, with about 753 cm2 of surface exposed to air. The body skin epidermis was thick (61 ± 3 µm, SEM), the stratum corneum alone taking a third of it (21 ± 3 µm). In contrast, the wing web skin epidermis was thinner at 9.8 ± 0.7 µm, with a stratum corneum measuring 4.1 ± 0.3 µm (41%). The wing capillaries in the wing web skin ran in the middle of the connective tissue core, with a resultant surface-capillary diffusion distance of 26.8 ± 3.2 µm. The rate of oxygen consumption (V,O2) of the wings alone and of the whole animal measured under light anaesthesia at ambient temperatures of 24 ºC and 33 ºC, averaged 6% and 10% of the total, respectively. Rate of carbon dioxide production had similar values. The membrane diffusing capacity for the wing web was estimated to be 0.019 ml O2 min,1 mmHg,1. We conclude that in Epomophorus wahlbergi, the wing web has structural modifications that permit a substantial contribution to the total gas exchange. [source] The ecological research needs of businessJOURNAL OF APPLIED ECOLOGY, Issue 2 2010Paul R. Armsworth Summary 1.,Businesses have an unrivalled ability to mobilize human, physical and financial capital, often manage large land holdings, and draw on resources and supply products that impact a wide array of ecosystems. Businesses therefore have the potential to make a substantial contribution to arresting declines in biodiversity and ecosystem services. To realize this potential, businesses require support from researchers in applied ecology to inform how they measure and manage their impacts on, and opportunities presented to them by, biodiversity and ecosystem services. 2.,We reviewed papers in leading applied ecology journals to assess the research contribution from existing collaborations involving businesses. We reviewed applications to, and grants funded by, the UK's Natural Environment Research Council for evidence of public investment in such collaborations. To scope opportunities for expanding collaborations with businesses, we conducted workshops with three sectors (mining and quarrying, insurance and manufacturing) in which participants identified exemplar ecological research questions of interest to their sector. 3.,Ten to fifteen per cent of primary research papers in Journal of Applied Ecology and Ecological Applications evidenced business involvement, mostly focusing on traditional rural industries (farming, fisheries and forestry). The review of UK research council funding found that 35% of applications mentioned business engagement, while only 1% of awarded grants met stricter criteria of direct business involvement. 4.,Some questions identified in the workshops aim to reduce costs from businesses' impacts on the environment and others to allow businesses to exploit new opportunities. Some questions are designed to inform long-term planning undertaken by businesses, but others would have more immediate commercial applications. Finally, some research questions are designed to streamline and make more effective those environmental policies that affect businesses. 5.,Business participants were forward-looking regarding ecological questions and research. For example, representatives from mining and quarrying companies emphasized the need to move beyond biodiversity to consider how ecosystems function, while those from the insurance sector stressed the importance of ecology researchers entering into new types of interdisciplinary collaboration. 6.,Synthesis and applications. Businesses from a variety of sectors demonstrated a clear interest in managing their impacts on, and exploiting opportunities created by, ecosystem services and biodiversity. To achieve this, businesses are asking diverse ecological research questions, but publications in leading applied ecology journals and research council funding reveal limited evidence of direct engagement with businesses. This represents a missed opportunity for ecological research findings to see more widespread application. [source] Diet of young-of-the-year bluefin tuna, Thunnus thynnus (Linnaeus, 1758), in the southern Tyrrhenian (Mediterranean) SeaJOURNAL OF APPLIED ICHTHYOLOGY, Issue 4 2004M. Sinopoli Summary The diet of juvenile bluefin tuna (Thunnus thynnus) caught 2 to 8 miles off NE Sicily was investigated in order to improve knowledge of the species' early life history. From 1998 to 2000, 107 specimens ranging from 63 to 495 mm (total length) were fished between July and November. Fishes were caught by trolling line or purse seine in a Fish Aggregating Devices (FADs) area 2 to 8 miles offshore and as by-catch of the purse-seine sardine fishery 2 to 4 miles offshore. Most frequently found items in the T. thynnus stomachs were fishes (84.5%), crustaceans (54.6%) and cephalopods (50.5%). The largest contribution in weight was provided by cephalopods (47.3%) and fishes (46.5%), while the most abundant items were fishes (51%), cephalopods (27.2%) and crustaceans (21.1%). These results suggest that young-of-the-year tuna have an essentially piscivorous diet, although invertebrate prey provide a substantial contribution to the food array. Prey show little relationship with FADs, although one prey species (blue runner, Caranx crysos) is associated with FADs in the Mediterranean. [source] A concept analysis of health-related quality of life in young people with chronic illnessJOURNAL OF CLINICAL NURSING, Issue 14 2008DipRes, Rachel M Taylor MSc Aims., To critique existing concept analyses of quality of life and develop a definition applicable for young people with chronic illness. Background., Quality of life is a commonly used phrase but there is no universal definition. Five perspectives of quality of life have been proposed: sociological, economic, psychological, philosophical and ethical. However, health has emerged as an important but distinct perspective. The nursing profession has made a substantial contribution to the understanding of the interrelationship of health and quality of life. Design., Literature review. Methods., A search on electronic databases to April 2007 was made using the terms ,quality of life' and ,concept analysis'. Papers were included in the review if they used a recognised method of concept analysis and were conducted by nurses. A new concept analysis was then performed specifically focusing on young people's experiences of living with chronic illness. Results., Eight concept analyses were identified, all of which had limitations. All the concept analyses were based on adult literature so did not take into consideration developmental changes, language level, or young people's construction of health and illness. The new concept analysis found that young people living with chronic illness generally view themselves and their lives in the same way as their healthy peers. While their aspirations are often constrained by illness and treatment the relationship between illness and life cannot be seen in isolation of development. Conclusion., Previous definitions of quality of life derived from concept analyses with adult populations do not adequately represent the experience of young people with chronic illnesses, but can be made more specific by incorporating important attributes such as developmental stage and the importance of peer group and family. Relevance to clinical practice., The current analysis provides a clear definition of quality of life from the health perspective which is specific for use with young people with chronic illness to guide practice and research. [source] Using Nanotechnology for the Substitution of Hazardous Chemical SubstancesJOURNAL OF INDUSTRIAL ECOLOGY, Issue 3 2008Challenges of Definition, Measurement Summary It is often assumed that nanotechnology (NT) holds the potential to provide a substantial contribution to the solution of various ecological problems, including high consumption of energy and materials and the generation of waste. However, problems surrounding the use and release of hazardous substances remain largely unexplored. For this reason, the Scientific Technical Option Assessment (STOA) Panel of the European Parliament initiated a study on "The Role of Nanotechnology in Chemical Substitution." The subject and aim of the study was an investigation into preexisting and potential applications of NT that could lead to a reduction in hazardous substances by providing substitutes for them. In terms of method, it was based on electronic searches of the literature, expert interviews, and an expert workshop. This article discusses the results of the project. It focuses on the methodological challenges and the principal problems resulting from a combination of the broad and ill-defined concept of NT and the specific concept of hazardous substances. The hazardous substances addressed had to be reduced to a manageable number, and the term substitution was understood according to the characteristics of NT and the way in which the latter could reduce the use of hazardous substances. Although several applications of NT were identified that could lead to a considerable reduction in the use of hazardous substances, ambiguities in both the concept of NT and the concept of substitution in relation to NT prevent a comprehensive assessment of the potential of NT in respect to substitution. [source] Multinational Retailers in China: Proliferating ,McJobs' or Developing Skills?*JOURNAL OF MANAGEMENT STUDIES, Issue 7 2006Jos Gamble abstract Much has been written on the nature of skills and the extent to which there is increased skills development or a deskilling of workers in modern workplaces. This paper broadens the debate and explores these issues in the novel context of UK- and Japanese- invested retailers' operations in China. Data derived from over two hundred interviews at twelve retail stores in six Chinese cities and questionnaires completed by almost eight hundred employees elicited contextualized accounts of interactive service workers' own perceptions of their training and skills development. It was found that these firms made a substantial contribution to skills development, fostered and enhanced both directly by company training and also through experiential workplace-based learning. It might be, however, that this constitutes an essential but ,one-off' increase in skills in transitional economies such as that of China. [source] OPRM1 Asn40Asp Predicts Response to Naltrexone Treatment: A Haplotype-Based ApproachALCOHOLISM, Issue 3 2009Gabor Oroszi Background:, Individualized pharmacotherapy requires identification of genetic variants predictive of treatment response. In OPRM1, Asn40Asp has been reported to be predictive of response to naltrexone treatment. Nevertheless, the in vitro function of the polymorphism remains elusive and over 300 OPRM1 sequence variants have been identified to date. Therefore we used a haplotype-based approach to capture information of other genetic variants that might predict treatment response to naltrexone in the COMBINE Study. Methods:, 5, nuclease genotyping assays (TaqMan®) were applied for 10 SNPs. Five-locus haplotypes in 2 OPRM1 haplotype blocks were assigned to Caucasian participants. The relationship of the haplotypes to medication reflected by "good clinical outcome" was analyzed in 306 Caucasians treated without Combined Behavioral Intervention and with either naltrexone or placebo. Results:, A significant haplotype by medication interaction (p = 0.03) was found in OPRM1 block 1. Naltrexone-treated alcoholics with haplotype AGCCC, the single haplotype carrying the Asp40 allele had the highest percent of good clinical outcome. When interaction of genotypes at each of the 5 loci comprising block 1 with medication was examined, only the Asn40/Asp40 and Asp40/Asp40 genotypes were found to significantly interact with naltrexone treatment. No haplotype by medication interaction was documented in OPRM1 block 2. Conclusions:, Our haplotype-based approach confirms that the single OPRM1 locus predictive of response to naltrexone treatment is Asn40Asp in exon 1. A substantial contribution of any other OPRM1 genetic variant to interindividual variations in response to naltrexone treatment (at least in terms of good clinical outcome) is not supported by our findings. [source] Toward a racial abyss: Eugenics, Wickliffe Draper, and the origins of The Pioneer FundJOURNAL OF THE HISTORY OF THE BEHAVIORAL SCIENCES, Issue 3 2002Michael G. Kenny professor of anthropology The Pioneer Fund was created in 1937 "to conduct or aid in conducting study and research into problems of heredity and eugenics,and problems of race betterment with special reference to the people of the United States." The Fund was endowed by Colonel Wickliffe Preston Draper, a New England textile heir, and perpetuates his legacy through an active program of grants, some of the more controversial in aid of research on racial group differences. Those presently associated with the Fund maintain that it has made a substantial contribution to the behavioral and social sciences, but insider accounts of Pioneer's history oversimplify its past and smooth over its more tendentious elements. This article examines the social context and intellectual background to Pioneer's origins, with a focus on Col. Draper himself, his concerns about racial degeneration, and his relation to the eugenics movement. In conclusion, it evaluates the official history of the fund. © 2002 Wiley Periodicals, Inc. [source] The Contributions of Political Life Events to Psychological Distress Among South AfricanPOLITICAL PSYCHOLOGY, Issue 3 2000Michelle Slone The psychological consequences of adverse political experiences among South African youth were studied in a sample of 540 black and white adolescents from two age groups, evenly divided by gender. Three questionnaires were administered, measuring exposure to political life events, the presence of symptoms of psychopathology, and stressful personal life events during the previous 5 years. The first hypothesis, predicting a substantial contribution of stressful political experiences to psychopathology, was strongly supported; when stressful personal life events were partialed out, a significant effect for political life events remained both on general distress and symptomatology indices. The second hypothesis of a linear relation between exposure to political life events and severity of distress was also confirmed. The findings underscore the enduring impact on children's mental health of past apartheid policies in South Africa specifically, and adverse political environments in general. [source] Thin film solar modules: the low cost, high throughput and versatile alternative to Si wafersPROGRESS IN PHOTOVOLTAICS: RESEARCH & APPLICATIONS, Issue 5 2006S. Hegedus Abstract Thin film solar cells (TFSC) have passed adolescence and are ready to make a substantial contribution to the world's electricity generation. They can have advantages over c-Si solar modules in ease of large area, lower cost manufacturing and in several types of applications. Factors which limit TFSC module performance relative to champion cell performance are discussed along with the importance of increased throughput and yield. The consensus of several studies is that all TFSC can achieve costs below 1,$/W if manufactured at sufficiently large scale >100,MW using parallel lines of cloned equipment with high material utilization and spray-on encapsulants. There is significant new commercial interest in TFSC from small investors and large corporations, validating the thin film approach. Unique characteristics are discussed which give TFSC an advantage over c-Si in two specific markets: small rural solar home systems and building integrated photovoltaic installations. TFSC have outperformed c-Si in annual energy production (kWhrs/kW), have demonstrated outdoor durability comparable to c-Si and are being used in MW scale installations worldwide. The merits of the thin film approach cannot be judged on the basis of efficiency alone but must also account for module performance and potential for low cost. TFSC advocates should promote their unique virtues compared to c-Si: lower cost, higher kWhr/kW output, higher battery charging current, attractive visual appearance, flexible substrates, long-term stability comparable to c-Si, and multiple pathways for deposition with room for innovation and evolutionary improvement. There is a huge market for TFSC even at today's efficiency if costs can be reduced. A brief window of opportunity exists for TFSC over the next few years due the Si shortage. The demonstrated capabilities and advantages of TFSC must be proclaimed more persistently to funding decision-makers and customers without minimizing the remaining challenges. Copyright © 2006 John Wiley & Sons, Ltd. [source] "Do You Have Anything to Add?"ANTHROPOLOGY & HUMANISM, Issue 1 2000Commentary on the Social Experience of Mental Illness, Narrative as Reflection This article argues that a phenomenological study of mental illness constructed from first-person subjective narratives can make a substantial contribution to our understanding of illness in terms of ordinary human experience. I suggest that the social experience of mental illness is primarily one of alienation and that this is both an internal and externally imposed experience. I conclude by proposing that the anthropological perspective,seeing the person within his or her wider cultural context, including both spatial and temporal dimensions,has the potential to generate new insights into how we might mitigate the alienating and depersonalizing effects of the mental illness experience. On another level, this article represents my attempt, as a mother, to come to terms with a mental health crisis within my own family. [source] The 423Q polymorphism of the X-linked inhibitor of apoptosis gene influences monocyte function and is associated with periodic feverARTHRITIS & RHEUMATISM, Issue 11 2009Massimo Ferretti Objective Hereditary periodic fever syndromes (HPFs) develop as a result of uncontrolled activation of the inflammatory response, with a substantial contribution from interleukin-1, or tumor necrosis factor , (TNF,). The HPFs include familial Mediterranean fever (FMF), hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), TNF receptor,associated syndrome (TRAPS), and cryopyrinopathies, which are attributable to mutations of the MEFV, MVK, TNFRSF1A, and CIAS1 genes, respectively. However, in many patients, the mutated gene has not been determined; therefore, the condition in these patients with an HPF-like clinical picture is referred to as idiopathic periodic fever (IPF). The aim of this study was to assess involvement of X-linked inhibitor of apoptosis (XIAP), which plays a role in caspase inhibition and NF-,B signaling, both of which are processes that influence the development of inflammatory cells. Methods The XIAP gene (X-linked) was sequenced in 87 patients with IPF, 46 patients with HPF (13 with HIDS, 17 with TRAPS, and 16 with FMF), and 182 healthy control subjects. The expression of different alleles was evaluated by sequencing XIAP -specific complementary DNA mini-libraries and by real-time polymerase chain reaction and Western blot analyses. The functional effect of XIAP on caspase 9 activity was assessed by a fluorimetric assay, and cytokine secretion was evaluated by enzyme-linked immunosorbent assay. Results Sequencing disclosed a 1268A>C variation that caused a Q423P amino acid substitution. The frequency of 423Q-homozygous female patients and 423Q-hemizygous male patients was significantly higher in the IPF group than in the control group (69% versus 51%; odds ratio 2.17, 95% confidence interval 1.23,3.87, P = 0.007), whereas no significant difference was detected in the HPF group (59%) compared with controls. In primary lymphocytes and transfected cell lines, 423Q, as compared with 423P, was associated with higher XIAP protein and messenger RNA expression and lower caspase 9 activation. In lipopolysaccharide-activated monocytes, 423Q was associated with higher secretion of TNF,. Conclusion These results suggest that 423Q is a predisposing factor for IPF development, possibly through its influence on monocyte function. [source] Structural asymmetry and intersubunit communication in muscle creatine kinaseACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2007Jeffrey F. Ohren The structure of a transition-state analog complex of a highly soluble mutant (R134K) of rabbit muscle creatine kinase (rmCK) has been determined to 1.65,Å resolution in order to elucidate the structural changes that are required to support and regulate catalysis. Significant structural asymmetry is seen within the functional homodimer of rmCK, with one monomer found in a closed conformation with the active site occupied by the transition-state analog components creatine, MgADP and nitrate. The other monomer has the two loops that control access to the active site in an open conformation and only MgADP is bound. The N-terminal region of each monomer makes a substantial contribution to the dimer interface; however, the conformation of this region is dramatically different in each subunit. Based on this structural evidence, two mutational modifications of rmCK were conducted in order to better understand the role of the amino-terminus in controlling creatine kinase activity. The deletion of the first 15 residues of rmCK and a single point mutant (P20G) both disrupt subunit cohesion, causing the dissociation of the functional homodimer into monomers with reduced catalytic activity. This study provides support for a structural role for the amino-terminus in subunit association and a mechanistic role in active-site communication and catalytic regulation. [source] The Ciona intestinalis genome: When the constraints are offBIOESSAYS, Issue 6 2003Linda Z. Holland The recent genome sequencing of a non-vertebrate deuterostome, the ascidian tunicate Ciona intestinalis, makes a substantial contribution to the fields of evolutionary and developmental biology.1 Tunicates have some of the smallest bilaterian genomes, embryos with relatively few cells, fixed lineages and early determination of cell fates. Initial analyses of the C. intestinalis genome indicate that it has been evolving rapidly. Comparisons with other bilaterians show that C. intestinalis has lost a number of genes, and that many genes linked together in most other bilaterians have become uncoupled. In addition, a number of independent, lineage-specific gene duplications have been detected. These new results, although interesting in themselves, will take on a deeper significance once the genomes of additional invertebrate deuterostomes (e.g. echinoderms, hemichordates and amphioxus) have been sequenced. With such a broadened database, comparative genomics can begin to ask pointed questions about the relationship between the evolution of genomes and the evolution of body plans. BioEssays 25:529,532, 2003. © 2003 Wiley Periodicals, Inc. [source] Conversation with Les DrewADDICTION, Issue 11 2001Article first published online: 15 SEP 200 In this occasional series we record the views and personal experiences of people who have specially contributed to the evolution of ideas in the Journal's field of interest. Dr Drew is an Australian psychiatrist who has made substantial contributions to drug and alcohol policy development in his country . [source] The relationship between local and regional diatom richness is mediated by the local and regional environmentGLOBAL ECOLOGY, Issue 3 2009Sophia I. Passy ABSTRACT Aim, In this continental study, species richness at local (LSR) and regional (RSR) scales was correlated and examined as a function of stream (local) and watershed (regional) environment in an effort to elucidate what factors control diatom biodiversity across scales. Location, Conterminous United States. Methods, Data on diatom richness, stream conditions and watershed properties were generated by the US Geological Survey. In the present investigation, RSR was estimated as the total diatom richness in a hydrologic study unit and, together with stream and watershed characteristics, was included in stepwise multiple regressions of LSR. The unique and shared contributions of RSR, stream and watershed environment to the explained variance in LSR were determined by variance partitioning. RSR was regressed against stream and basin features averaged per study unit. Results, LSR responded most strongly to variability in stream manganese concentration and RSR. Other predictors included stream discharge and iron concentration, soil organic matter content and fertilization, and proportions of open water, barren land and forest in the watershed. Variance partitioning revealed that RSR had the lowest independent contribution to explained variance in LSR. Multiple regressions identified average stream iron concentration as the most important predictor of RSR. Main conclusions, Local micronutrient concentration was the major predictor of LSR, followed by RSR. Since average micronutrient supply in the region was the chief determinant of RSR, it is proposed that micronutrients had both a direct effect on LSR and an indirect effect through RSR. The same argument is extended to watershed features with an impact on stream trophic status, because of their substantial contributions to the explained variance in both LSR and RSR. Considering that the major proportion of LSR variance explained by RSR originated from the covariance of RSR with stream and watershed properties, it is concluded that the LSR,RSR relationship was mediated by the local and regional environment. [source] Corporate giving in the USA: a model for meeting Russia's expanding social needs?INTERNATIONAL JOURNAL OF NONPROFIT & VOLUNTARY SECTOR MARKETING, Issue 3 2004Karen King In the USA, corporations make substantial contributions to public-serving organisations with no expectation of financial gain. This paper explores the factors that have encouraged corporate giving in the USA and compares them to circumstances in the emerging capitalist economy of Russia. The outlook for the emergence of a corporate giving model in Russia similar to that of the USA is poor, but improving. To make it work, organisational recipients of corporate generosity need to trust their benefactors, and corporations need to believe that their contributions of surplus profits make good business sense. Copyright © 2004 Henry Stewart Publications [source] Ranking institutional settings based on publications in community psychology journalsJOURNAL OF COMMUNITY PSYCHOLOGY, Issue 8 2007Leonard A. Jason Two primary outlets for community psychology research, the American Journal of Community Psychology and the Journal of Community Psychology, were assessed to rank institutions based on publication frequency and scientific influence of publications over a 32-year period. Three specific periods were assessed (1973,1983, 1984,1994, 1995,2004). Findings indicate that there were a large group of institutions that published articles during these periods. Those academic institutions that had the most published articles as well as the largest influence, based on citations by other authors, were identified. Using archival data from the community psychology literature represents one approach for identifying those settings that made substantial contributions to the development and growth of the field. © 2007 Wiley Periodicals, Inc. J Comm Psychol 35: 967,979, 2007. [source] Using community-based participatory research to design and initiate a study on immigrant worker health and safety in San Francisco's Chinatown restaurantsAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2010Meredith Minkler DrPH Abstract Background Restaurant workers have among the highest rates of work-related illness and injury in the US, but little is known about the working conditions and occupational health status of Chinese immigrant restaurant workers. Methods Community-based participatory research (CBPR) was employed to study restaurant working conditions and worker health in San Francisco's Chinatown. A community/academic/health department collaborative was formed and 23 restaurant workers trained on research techniques and worker health and safety. A worker survey instrument and a restaurant observational checklist were collaboratively developed. The checklist was piloted in 71 Chinatown restaurants, and the questionnaire administered to 433 restaurant workers. Results Restaurant workers, together with other partners, made substantial contributions to construction of the survey and checklist tools and improved their cultural appropriateness. The utility of the checklist tool for restaurant-level data collection was demonstrated. Conclusions CBPR holds promise for both studying worker health and safety among immigrant Chinese restaurant workers and developing culturally appropriate research tools. A new observational checklist also has potential for restaurant-level data collection on worker health and safety conditions. Am. J. Ind. Med. 53:361,371, 2010. © 2010 Wiley-Liss, Inc. [source] Martin K. Starr: A Visionary Proponent for System Integration, Modular Production, and Catastrophe AvoidancePRODUCTION AND OPERATIONS MANAGEMENT, Issue 1 2007Sushil Gupta Martin K. Starr facilitated the creation of an identity for production and operations management (POM) as an academic discipline. This paper aims to summarize Starr's substantial contributions to scholarly inquiry on system integration and interfunctional coordination, modular production, and catastrophe avoidance. Even after four decades, we describe how his legacy in these areas continues to define several major drivers of operations and supply chain management research and practice. Starr has influenced several generations of students, professors, and executives with his writings, teaching, and leadership roles in the POM community that include 32 years on the faculty of the Columbia School of Business, 15 years as Editor-in-Chief of Management Science, and presidency of the Production and Operations Management Society. [source] A guide map to the terrain of gift valuePSYCHOLOGY & MARKETING, Issue 8 2001Derek Larsen This article integrates a broad range of gift-giving literature into a conceptual framework that puts the all too often overlooked construct of personal value at its core. Although there have been substantial contributions from the fields of anthropology, sociology, economics, and consumer behavior, efforts to model gift giving have failed to put the value of the gift-giving experience at the center of the exchange. Within this article, a model of the gift-giving experience that overcomes this critical shortcoming is proposed. The model establishes clear categories for breaking the giving process into easily examinable elements, and it is argued that although the concept of value is not a simple one, it should be central to any examination of the gift-giving phenomenon. © 2001 John Wiley & Sons, Inc. [source] Study Designs and Evaluation Models for Emergency Department Public Health ResearchACADEMIC EMERGENCY MEDICINE, Issue 11 2009Kerry B. Broderick MD Abstract Public health research requires sound design and thoughtful consideration of potential biases that may influence the validity of results. It also requires careful implementation of protocols and procedures that are likely to translate from the research environment to actual clinical practice. This article is the product of a breakout session from the 2009 Academic Emergency Medicine consensus conference entitled "Public Health in the ED: Screening, Surveillance, and Intervention" and serves to describe in detail aspects of performing emergency department (ED)-based public health research, while serving as a resource for current and future researchers. In doing so, the authors describe methodologic features of study design, participant selection and retention, and measurements and analyses pertinent to public health research. In addition, a number of recommendations related to research methods and future investigations related to public health work in the ED are provided. Public health investigators are poised to make substantial contributions to this important area of research, but this will only be accomplished by employing sound research methodology in the context of rigorous program evaluation. [source] | ||||||||||||||||||||||||||||