bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological networks and epistasis in genome-wide association studies
Authors: Emily Mathieu , Schauser Leif , Mailund Thomas , Schierup Mikkel 
Published: July 2007

AbstractOver the last few years, technological improvements have made possible the genotyping of hundreds of thousands of SNPs, enabling whole-genome association studies. The first genome-wide association studies have recently been completed to detect causal variant for complex traits. Although increasing evidence suggests that interaction between loci, such as epistasis between two loci, should be considered, most of these studies proceed by considering each SNP independently. One reason for this choice is that looking at all pairs of SNPs increases dramatically the number of tests (approximatively 50 billions of tests for a 300,000 SNPs data set) that faces with computational limitation and strong multiple testing correction.We proposed to reduce the number of tests by focusing on pairs of SNPs that belong to genes known to interact in some metabolic network. Although some interactions might be missed, these pairs of genes are good candidates for epistasis. Furthermore the use of protein interaction databases (such as the STRING database) may reduce the number of tests by a factor of 5,000.Results using this approach will be presented on simulated data sets and on public data sets.
B cells modulate T cells so as to favour T helper type 1 and CD8+ T‐cell responses in the acute phase of Trypanosoma cruzi infection
Authors: Cardillo Fabiola , Postol Edilberto , Nihei Jorge , Aroeira Luiz S. , Nomizo Auro , Mengel José 
Published: July 2007

SummaryIn this study, we have evaluated the production of pro‐ and anti‐inflammatory cytokines and the formation of central and effector memory T cells in mice lacking mature B cells (muMT KO). The results show that Trypanosoma cruzi infection in C57Bl/6mμ MT KO mice is intensified in relation to control mice and this exacerbation is related to low levels of inflammatory cytokines produced during the acute infection and the lower numbers of central and effector memory CD4+ and CD8+ T cells generated during the acute phase of the infection. In addition, a marked reduction in the CD8+ T‐cell subpopulation was observed in muMT KO infected mice. In agreement to this, the degree of tissue parasitism was increased in muMT mice and the tissue inflammatory response was much less intense in the acute phase of the infection, consistent with a deficit in the generation of effector T cells. Flow cytometry analysis of the skeletal muscle inflammatory infiltrate showed a predominance of CD8+ CD45Rb low in B‐cell‐sufficient C57Bl/6 mice, whereas the preponderant cell type in muMT KO skeletal muscle inflammatory infiltrate was CD4+ T cells. In addition, CD8+ T cells found in skeletal muscle from muMT KO infected mice were less activated than in control B‐cell sufficient infected mice. These results suggest that B cells may participate in the generation of effector/memory T cells. In addition and more importantly, B cells were crucial in the maintenance of central and effector memory CD8+ T cell, as well as the determination of the T cell cytokine functional pattern, and they may therefore account for critical aspects of the resistance to intracellular pathogens, such as T. cruzi.
Sublingual ‘Oral Tolerance’ Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Regulatory T Cells that Induce Apoptosis and Depletion of Effector T Cells
Authors: Sun J.‐B. , Czerkinsky C. , Holmgren J. 
Published: July 2007

AbstractSublingual (s.l.) immunotherapy has in the last decade emerged as an effective approach to desensitize patients with pollen, food and insect sting allergies. This treatment has recently also attracted interest as a potential modality to control self‐reactive T‐cell responses associated with autoimmune disorders. Here, we show that s.l. administration of ovalbumin (OVA) conjugated to cholera toxin B subunit (CTB) (OVA/CTB) can efficiently suppress peripheral effector T (Teff) cell responses to OVA in mice that had adoptively received OVA‐specific T‐cell receptor (TCR) transgenic CD4+ T cells, and that the suppression was associated with the development of OVA‐specific Foxp3+CD25+CD4+ regulatory T (Treg) cells as well as with apoptosis (Annexin V+) and depletion of OVA‐specific Teff cells in peripheral lymph nodes. The induction of Teff cell apoptosis by s.l. OVA/CTB administration was found to be critically dependent on CD25+ Treg cells but independent of IL‐10 production. Our results suggest that s.l administration of a CTB‐conjugated antigen can efficiently induce peripheral Teff cell tolerance through the induction of antigen‐specific Treg cells that both inhibit Teff cell proliferation and cytokine production and induce Teff cell apoptosis and depletion.
Low antibiotic resistance rates in Staphylococcus aureus, Escherichia coli and Klebsiella spp but not in Enterobacter spp and Pseudomonas aeruginosa: a prospective observational study in 14 Swedish ICUs over a 5‐year period
Authors: Hanberger H. , Burman L. G. , Cars O. , Erlandsson M. , Gill H. , Nilsson L. E. , Nordlinder D. , Walther S. M. ,   ICU STRAMA study group
Published: July 2007

Background:  Intensive care units (ICUs) are hot zones for emergence and spread of antibiotic resistance because of frequent invasive procedures, antibiotic usage and transmission of bacteria. We report prospective data on antibiotic use and bacterial resistance from 14 academic and non‐academic ICUs, participating in the ICU‐STRAMA programme 1999–2003.Methods:  The quantity of antibiotics delivered to each ICU was calculated as defined daily doses per 1000 occupied bed days (DDD1000). Specimens for culture were taken on clinical indications and only initial isolates were considered. Species‐related breakpoints according to the Swedish Reference Group for Antibiotics were used. Antibiotic resistance was defined as the sum of intermediate and resistant strains.Results:  Mean antibiotic use increased from 1245 DDD1000 in 1999 to 1510 DDD1000 in 2003 (P = 0.11 for trend). Of Staphylococcus aureus, 0–1.8% were methicillin resistant (MRSA). A presumptive extended spectrum beta‐lactamase (ESBL) phenotype was found in <2.4% of Escherichia coli, based on cefotaxime susceptibility, except a peak in 2002 (4.6%). Cefotaxime resistance was found in 2.6–4.9% of Klebsiella spp. Rates of resistance among Enterobacter spp. to cefotaxime (20–33%) and among Pseudomonas aeruginosa to imipenem (22–33%) and ciprofloxacin (5–21%) showed no time trend.Conclusion:  MRSA and cefotaxime‐resistant E. coli and Klebsiella spp strains were few despite high total antibiotic consumption. This may be the result of a slow introduction of resistant strains into the ICUs, and good infection control. The cause of imipenem and ciprofloxacin resistance in P. aeruginosa could reflect the increased consumption of these agents plus spread of resistant clones.
Therapeutic hypothermia after cardiac arrest: implementation and outcome in Finnish intensive care units
Authors: Oksanen T. , Pettilä V. , Hynynen M. , Varpula T. ,   Intensium Consortium study group
Published: July 2007

Background:  Therapeutic hypothermia (TH) has been shown to increase survival after out‐of‐hospital resuscitation. The aim of our study was to find out nationwide implementation and the actual utilization of TH after cardiac arrest in Finnish intensive care units (ICUs). We also determined the outcomes and describe demographic variables of the patients treated with TH.Methods:  We analyzed a nationwide prospective database and included all adult patients (1555) treated in ICUs after cardiac arrest during 2004 and 2005.Results:  During 2004 and 2005, 407 patients were treated with TH and TH was used in 19 out of the 20 ICUs. The proportion of cardiac arrest patients treated with TH had increased from 4% in 2002 to 28% in 2005. The incidence of cardiac arrest patients admitted to ICUs was 15/100,000 inhabitants/year. The use of TH varied in different areas of the country from 3.4 to 5.0/100,000 inhabitants/year. In‐hospital mortality of TH patients was 32.7% and increased from 13.2% in age group <45 years to 46.0% in age group >75 years (P = 0.0002). Six‐month survival was 55.3%. Median (interquartile range) length of stay in the ICU was 3.7 (2.7–5.3) days.Conclusion:  In Finland, TH is implemented in almost all ICUs but it is applied only to a selected group of patients. Six months after cardiac arrest, more than half of the patients treated with TH were alive. Among patients treated with TH, younger patients had lower in‐hospital mortality.
Policy statement on iron deficiency in pre‐school‐aged children
Authors: Grant Cameron C , Wall Clare R , Brewster David , Nicholson Ross , Whitehall John , Super Leanne , Pitcher Lydia 
Published: July 2007

Aim: We aimed to develop policy in relation to three areas: (i) the diagnosis of iron deficiency; (ii) maternal–infant issues and the prevention of iron deficiency; and (iii) the treatment of iron deficiency.Methods: Within each of these topic areas we completed a literature review and developed recommendations to help direct activities of the Royal Australasian College of Physicians, update paediatricians and guide clinical practice.Results: Iron deficiency can be defined using cut‐off values for laboratory measures of iron status or, if an intercurrent infection is not present, by demonstrating a response to a therapeutic trial of iron. The appropriate measures of iron status vary depending upon the presence of intercurrent infection. Full‐term babies are born with iron stores sufficient to meet their needs to age 4–6 months but premature infants are not. After age 6 months infants are dependent upon dietary iron from complementary foods even with continued breastfeeding. Infants <33 weeks gestation or <1800 g birthweight should receive iron from 4 weeks of age. In most settings recommended treatment of iron deficiency is with oral ferrous sulphate as a single or twice daily dose of between 3 and 6 mg/kg/day.Conclusions: Iron deficiency is prevalent and an important determinant of child health. Precise and accurate diagnosis remains challenging. Iron supplementation is required for premature and low‐birthweight infants. Oral iron salts remain the recommended treatment of choice in most instances.
Emergence and disappearance of microarcsecond structure in the scintillating quasar J1819+3845
Authors: Macquart J.-P. , De Bruyn A. G. 
Published: July 2007

Abstract
The 4.8-GHz light curves of the scintillating intraday variable quasar J1819+3845 during 2004–2005 exhibit sharp structure, down to a time-scale of 15 min, that was absent from light curves taken prior to this period and from the 2006 light curves. Analysis of the light curve power spectra show that the variations must be due to the emergence of new structure in the source. The power spectra yield a scattering screen distance of 3.8 ± 0.3 pc for a best-fitting vISS= 59 ± 0.5 km s−1 or 2.0 ± 0.3 pc for the scintillation velocity reported by Dennett-Thorpe & de Bruyn. The scattering medium is required to be exceptionally turbulent, with C2N≳ 0.7 ΔL−1pc m−20/3 for scattering material of thickness ΔLpc pc along the ray path. The 2004 power spectrum can be explained in terms of a double source with a component separation 240 ± 15 μas in 2004.
20(S)-Hydroxycholesterol Inhibits PPARγ Expression and Adipogenic Differentiation of Bone Marrow Stromal Cells Through a Hedgehog-Dependent Mechanism
Authors: Kim Woo-Kyun , Meliton Vicente , Amantea Christopher M , Hahn Theodore J , Parhami Farhad 
Published: July 2007

Abstract
Specific oxysterols have been shown to be pro-osteogenic and anti-adipogenic. However, the molecular mechanism(s) by which oxysterols inhibit adipogenic differentiation is unknown. We show that the anti-adipogenic effects of osteogenic oxysterol, 20(S)-hydroxycholesterol, are mediated through a hedgehog-dependent mechanism(s) and are associated with inhibition of PPARγ expression.
Introduction: Multipotent bone marrow stromal cells (MSCs) are common progenitors of osteoblasts and adipocytes. A reciprocal relationship between osteogenic and adipogenic differentiation may explain the increased adipocyte and decreased osteoblast formation in aging and osteoporosis. We have previously reported that specific oxysterols stimulate osteogenic differentiation of MSCs while inhibiting their adipogenic differentiation.
Materials and Methods: The M2–10B4 (M2) murine pluripotent bone MSC line was used to assess the inhibitory effects of 20(S)-hydroxycholesterol (20S) and sonic hedgehog (Shh) on peroxisome proliferator-activated receptor γ (PPARγ) and adipogenic differentiation. All results were analyzed for statistical significance using ANOVA.
Results and Conclusions: Treatment of M2 cells with the osteogenic oxysterol 20S completely inhibited adipocyte formation induced by troglitazone after 10 days. PPARγ mRNA expression assessed by RT-qPCR was significantly induced by Tro after 48 (5-fold) and 96 h (130-fold), and this induction was completely inhibited by 20S. In contrast, 20S did not inhibit PPARγ transcriptional activity in M2 cells overexpressing PPARγ and retinoid X receptor (RXR). To elucidate the molecular mechanism(s) by which 20S inhibits PPARγ expression and adipogenic differentiation, we focused on the hedgehog signaling pathway, which we previously showed to be the mediator of osteogenic responses to oxysterols. The hedgehog signaling inhibitor, cyclopamine, reversed the inhibitory effects of 20S and Shh on troglitazone-induced adipocyte formation in 10-day cultures of M2 cells by 70% and 100%, respectively, and the inhibitory effect of 20S and Shh on troglitazone-induced PPARγ expression was fully reversed at 48 h by cyclopamine. Furthermore, 20S and Shh greatly inhibited PPARγ2 promoter activity induced by CCAAT/enhancer-binding protein α overexpression. These studies show that, similar to the induction of osteogenesis, the inhibition of adipogenesis in murine MSCs by the osteogenic oxysterol, 20S, is mediated through a hedgehog-dependent mechanism(s).
Bull Trout Population Responses to Reductions in Angler Effort and Retention Limits
Authors: Parker Brian R. , Schindler David W. , Wilhelm Frank M. , Donald David B. 
Published: July 2007

Abstract
We compared historical (1977–1980) and recent (1997–2001) abundance, catch-per-unit-effort (CPUE), and growth data to assess whether the implementation of restrictive sportfishing regulatory regimes in the 1990s led to changes in abundance and population structure of bull trout Salvelinus confluentus in two small Rocky Mountain lakes in Alberta, Canada. For remote Harrison Lake, we used changes in gill-net CPUE to infer a fivefold increase in bull trout abundance after closure of an access road and implementation of catch-and-release (CR) regulations. Bull trout growth rates decreased as their abundance increased. All large (fork length &gt; 420 mm), old (age &gt;12) bull trout were eliminated after regulatory changes were imposed. Reductions in prey abundance and size as bull trout abundance increased probably contributed to the demise of the large bull trout. For road-accessible Osprey Lake, no change in bull trout mark–recapture abundance estimates or growth rates were observed despite implementation of CR regulations and, later, closure of the lake to angling. We speculate that illegal angling and migration of bull trout between Osprey Lake and its tributary streams limited abundance responses at this site. A variety of site-specific factors, including ease of access, angler noncompliance with regulations, and local metapopulation structure of bull trout, led to variable bull trout population responses to the implementation of restrictive angling regulations. Active advertisement and enforcement of regulations may be required to achieve increased bull trout abundance at small, easily accessible waterbodies.
Leadership Ethics: Mapping the Territory
Authors: Ciulla Joanne B. 
Published: July 2007

Abstract:In this paper I argue that a greater understanding of the part of ethics in leadership will improve leadership studies. Debates over the definition of leadership are really debates over what researchers think constitutes good leadership. The ultimate question is not “What is leadership?” but “What is good leadership?” The word good is refers to both ethics and competence. Research into leadership ethics would explore the ethical issues of current leadership research, serve as a critical study of the field, analyze and expand normative theories of leadership, and develop new theories, research questions and ways of thinking about leadership.
Promoting Honesty in Negotiation: An Exercise in Practical Ethics
Authors: Cramton Peter C. , Dees J. Gregory 
Published: July 2007

In a competitive and morally imperfect world, business people are often faced with serious ethical challenges. Harboring suspicions about the ethics of others, many feel justified in engaging in less-than-ideal conduct to protect their own interests. The most sophisticated moral arguments are unlikely to counteract this behavior. We believe that this morally defensive behavior is responsible, in large part, for much undesirable deception in negotiation. Drawing on recent work in the literature of negotiations, we present some practical guidance on how negotiators might build trust, establish common interests, and secure credibility for their statements, thereby promoting honesty. We also point out the types of social and institutional arrangements, many of which have become commonplace, that work to promote credibility, trust, and honesty in business dealings. Our approach is offered not only as a specific response to the problem of deception in negotiation, but as one model of how research in business ethics might offer constructive advice to practitioners.…there is such a gap between how one lives and how one ought to live that anyone who abandons what is done for what ought to be done learns his ruin rather than his preservation …—Niccolo MachiavelliWe must make the world honest before we can honestly say to our children that honesty is the best policy.—George Bernard Shaw
The Challenge of Wealth: Jewish Business Ethics
Authors: Tamari Meir 
Published: July 2007

Abstract:Jewish business ethics in Israel addresses two major sources of economic immorality—unbounded desire and fear of economic uncertainty—through enforcement and spiritual education. Business is seen as a path to sanctity, when time is set apart for religious study, wealth is seen as originating from God, the vulnerable are protected against fraud and theft, charity is seen as an obligation, and mercy towards debtors is tempered by justice.
Catholic Social Teaching in an ERA of Economic Globalization: A Resource for Business Ethics
Authors: McCann Dennis P. 
Published: July 2007

Abstract:The paper attempts to provide a basis for exploring the continued relevance of Catholic social teaching to business ethics, by interpreting the historic development of a Catholic work ethic and the traditions of Catholic social teaching in light of contemporary discussions of economic globalization, notably those of Robert Reich and Peter Drucker. The paper argues that the Catholic work ethic and the Church’s tradition of social teaching has evolved dynamically in response to the structural changes involved in the history of modern economic development, and thus is well poised to speak to the ethical challenges implicit in the advent of a knowledge-based society. In order to test this thesis, the author sketches an approach to the ethical challenge of corporate downsizing that he believes illustrates the continued relevance of Catholic social teaching to business ethics.
Moral Hazards on the Road to the “Virtual” Corporation
Authors: Jones Thomas M. , Bowie Norman E. 
Published: July 2007

Abstract:In recent years, two topics have made prominent debuts in the management literature—“virtual” corporations and trust within and among organizations. These two themes are related in that trust is important to the success of the virtual corporation. This article argues that confidence in the development of virtual corporations may be premature because of what we call the Virtual Corporation Paradox. This paradox can be succinctly stated: the short-term, transient deal-making on which the efficiency of the virtual corporation rests greatly impedes the development of the mutually trusting and cooperative relationships on which its success depends. We examine both economic and sociological explanations for the emergence of trust in similar situations and find both deficient. We conclude that the success of virtual corporations will ultimately depend on an ethics-based form of corporate “character” that allows firms to develop trusting relationships without the usual safeguards or social norms.
Stakeholders and the Moral Responsibilities of Business
Authors: Langtry Bruce 
Published: July 2007

Abstract:This paper discusses the normative ethical theory of the business firm advanced principally by William E. Evan and R. Edward Freeman. According to their stakeholder theory, the firm should be managed for the benefit of its stakeholders: indeed, management has a fiduciary obligation to stakeholders to act as their agent. In this paper I seek to clarify the theory by discussing the concept of a stakeholder and by distinguishing stakeholder theory from two varieties of stockholder theory—I call them ‘pure’ and ‘tinged.’ I argue that the distinctive claims of stakeholder theory, as contrasted with tinged stockholder theories, have been inadequately supported by argument.
Social Contract Theory and Gender Discrimination: Some Reflections on the Donaldson/Dunfee Model
Authors: Mayer Don , Cava Anita 
Published: July 2007

Abstract:This paper relates Donaldson and Dunfee’s Integrative Social Contracts Theory to the problem of gender discrimination. We make the assumption that multinational managers might seek some guidance from ISCT to resolve ethical issues of gender discrimination in countries indifferent or hostile to gender equality. The role of Donaldson and Dunfee’s “hypernorms” seems especially crucial, and we find that, under their writings thus far, no “hypernorms” exist to make unethical the most blatant acts of sex discrimination in a host country whose local norms tolerate such discrimination. The genesis of “hypernorms” as “global moral minimums” is recounted, and specific application of ISCT to a familiar ethics case (“A Foreign Assignment”) is provided.
Making Business Ethics Practical
Authors: Cavanagh Gerald F. , Moberg Dennis J. , Velasquez Manuel 
Published: July 2007

Abstract:Our critics confuse the role normative ethical theory can take in business ethics. We argue that as a practical discipline, business ethics must focus on norms, not the theories from which the norms derive. It is true that our original work is defective, but not in its form, but in its neglect of contemporary advances in feminist ethics.
The Place of Ethics in Business: Shifting Paradigms?
Authors: Shepard Jon M. , Shepard Jon , Wimbush James C. , Stephens Carroll U. 
Published: July 2007

Abstract:This article uses concepts from sociology, history, and philosophy to explore the shifting relationship between moral values and business in the Western world. We examine the historical roots and intellectual underpinnings of two major business-society paradigms in ideal-type terms. In pre-industrial Western society, we argue that business activity was linked to society’s values of morality (the moral unity paradigm)—for good or for ill. With the rise of industrialism, we contend that business was freed from moral constraints by the alleged “invisible hand” of efficient markets (the amoral theory of business). Armed with this understanding of the intellectual history of the moral unity and amoral business-society paradigms, we suggest that some variant of the moral unity paradigm may be recurring in post-industrial society.