351 research outputs found

    Self dual models and mass generation in planar field theory

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    We analyse in three space-time dimensions, the connection between abelian self dual vector doublets and their counterparts containing both an explicit mass and a topological mass. Their correspondence is established in the lagrangian formalism using an operator approach as well as a path integral approach. A canonical hamiltonian analysis is presented, which also shows the equivalence with the lagrangian formalism. The implications of our results for bosonisation in three dimensions are discussed.Comment: 15 pages,Revtex, No figures; several changes; revised version to appear in Physical Review

    Zeta function regularization for a scalar field in a compact domain

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    We express the zeta function associated to the Laplacian operator on Sr1×MS^1_r\times M in terms of the zeta function associated to the Laplacian on MM, where MM is a compact connected Riemannian manifold. This gives formulas for the partition function of the associated physical model at low and high temperature for any compact domain MM. Furthermore, we provide an exact formula for the zeta function at any value of rr when MM is a DD-dimensional box or a DD-dimensional torus; this allows a rigorous calculation of the zeta invariants and the analysis of the main thermodynamic functions associated to the physical models at finite temperature.Comment: 19 pages, no figures, to appear in J. Phys.

    DREDed Anomaly Mediation

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    We offer a guide to dimensional reduction (DRED) in theories with anomaly mediated supersymmetry breaking. Evanescent operators proportional to epsilon arise in the bare Lagrangian when it is reduced from d=4 to d= (4-2 epsilon) dimensions. In the course of a detailed diagrammatic calculation, we show that inclusion of these operators is crucial. The evanescent operators conspire to drive the supersymmetry-breaking parameters along anomaly-mediation trajectories across heavy particle thresholds, guaranteeing the ultraviolet insensitivity.Comment: 24 pages. 10 figures. Uses Axodraw. Reference adde

    Radiocarbon Evidence for the Importance of Surface Vegetation on Fermentation and Methanogenesis in Contrasting Types of Boreal Peatlands

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    We found a consistent distribution pattern for radiocarbon in dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), and methane replicated across spatial and temporal scales in northern peatlands from Minnesota to Alaska. The 14C content of DOC is relatively modern throughout the peat column, to depths of 3 m. In sedge-dominated peatlands, the 14C contents of the products of respiration, CH4 and DIC, are essentially the same and are similar to that of DOC. In Sphagnum- and woody plant-dominated peatlands with few sedges, however, the respiration products are similar but intermediate between the 14C contents of the solid phase peat and the DOC. Preliminary data indicates qualitative differences in the pore water DOC, depending on the extent of sedge cover, consistent with the hypothesis that the DOC in sedge-dominated peatlands is more reactive than DOC in peatlands where Sphagnum or other vascular plants dominate. These data are supported by molecular level analysis of DOC by ultrahigh-resolution mass spectrometry that suggests more dramatic changes with depth in the composition of DOC in the sedge-dominated peatland pore waters relative to changes observed in DOC where Sphagnum dominates. The higher reactivity of DOC from sedge-dominated peatlands may be a function of either different source materials or environmental factors that are related to the abundance of sedges in peatlands

    Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

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    Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

    Personal identity (de)formation among lifestyle travellers: A double-edged sword?

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    This article explores the personal identity work of lifestyle travellers – individuals for whom extended leisure travel is a preferred lifestyle that they return to repeatedly. Qualitative findings from in-depth semi-structured interviews with lifestyle travellers in northern India and southern Thailand are interpreted in light of theories on identity formation in late modernity that position identity as problematic. It is suggested that extended leisure travel can provide exposure to varied cultural praxes that may contribute to a sense of social saturation. Whilst a minority of the respondents embraced a saturation of personal identity in the subjective formation of a cosmopolitan cultural identity, several of the respondents were paradoxically left with more identity questions than answers as the result of their travels

    Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

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    Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

    Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

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    IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

    Effectiveness of Action in India to Reduce Exposure of Gyps Vultures to the Toxic Veterinary Drug Diclofenac

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    Contamination of their carrion food supply with the non-steroidal anti-inflammatory drug diclofenac has caused rapid population declines across the Indian subcontinent of three species of Gyps vultures endemic to South Asia. The governments of India, Pakistan and Nepal took action in 2006 to prevent the veterinary use of diclofenac on domesticated livestock, the route by which contamination occurs. We analyse data from three surveys of the prevalence and concentration of diclofenac residues in carcasses of domesticated ungulates in India, carried out before and after the implementation of a ban on veterinary use. There was little change in the prevalence and concentration of diclofenac between a survey before the ban and one conducted soon after its implementation, with the percentage of carcasses containing diclofenac in these surveys estimated at 10.8 and 10.7%, respectively. However, both the prevalence and concentration of diclofenac had fallen markedly 7–31 months after the implementation of the ban, with the true prevalence in this third survey estimated at 6.5%. Modelling of the impact of this reduction in diclofenac on the expected rate of decline of the oriental white-backed vulture (Gyps bengalensis) in India indicates that the decline rate has decreased to 40% of the rate before the ban, but is still likely to be rapid (about 18% year−1). Hence, further efforts to remove diclofenac from vulture food are still needed if the future recovery or successful reintroduction of vultures is to be feasible

    Self-renewal and chemotherapy resistance of p75NTR positive cells in esophageal squamous cell carcinomas

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    <p>Abstract</p> <p>Background</p> <p>p75<sup>NTR </sup>has been used to isolate esophageal and corneal epithelial stem cells. In the present study, we investigated the expression of p75<sup>NTR </sup>in esophageal squamous cell carcinoma (ESCC) and explored the biological properties of p75<sup>NTR+ </sup>cells.</p> <p>Methods</p> <p>p75<sup>NTR </sup>expression in ESCC was assessed by immunohistochemistry. p75<sup>NTR+ </sup>and p75<sup>NTR- </sup>cells of 4 ESCC cell lines were separated by fluorescence-activated cell sorting. Differentially expressed genes between p75<sup>NTR+ </sup>and p75<sup>NTR- </sup>cells were determined by real-time quantitative reverse transcription-PCR. Sphere formation assay, DDP sensitivity assay, <sup>64</sup>copper accumulation assay and tumorigenicity analysis were performed to determine the capacity of self-renewal, chemotherapy resistance and tumorigenicity of p75<sup>NTR+ </sup>cells.</p> <p>Results</p> <p>In ESCC specimens, p75<sup>NTR </sup>was found mainly confined to immature cells and absent in cells undergoing terminal differentiation. The percentage of p75<sup>NTR+ </sup>cells was 1.6%–3.7% in Eca109 and 3 newly established ESCC cell lines. The expression of Bmi-1, which is associated with self-renewal of stem cells, was significantly higher in p75<sup>NTR+ </sup>cells. p63, a marker identified in keratinocyte stem cells, was confined mainly to p75<sup>NTR+ </sup>cells. The expression of CTR1, which is associated with cisplatin (DDP)-resistance, was significantly decreased in p75<sup>NTR+ </sup>cells. Expression levels of differentiation markers, such as involucrin, cytokeratin 13, β1-integrin and β4-integrin, were lower in p75<sup>NTR+ </sup>cells. In addition, p75<sup>NTR+ </sup>cells generated both p75<sup>NTR+ </sup>and p75<sup>NTR- </sup>cells, and formed nonadherent spherical clusters in serum-free medium supplemented with growth factors. Furthermore, p75<sup>NTR+ </sup>cells were found to be more resistant to DDP and exhibited lower <sup>64</sup>copper accumulation than p75<sup>NTR- </sup>cells.</p> <p>Conclusion</p> <p>Our results demonstrated that p75<sup>NTR+ </sup>cells possess some characteristics of CSCs, namely, self-renewal and chemotherapy resistance. Chemotherapy resistance of p75<sup>NTR+ </sup>cells may probably be attributable to decreased expression of CTR1.</p
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