6,447 research outputs found
Polarity-dependent reversible resistance switching in Ge–Sb–Te phase-change thin films
In this paper, we demonstrate reversible resistance switching in a capacitorlike cell using a Ge–Sb–Te film that does not rely on amorphous-crystalline phase change. The polarity of the applied electric field switches the cell resistance between lower- and higher-resistance states, as was observed in current-voltage characteristics. Moreover, voltage pulses less than 1.25 V showed this switching within time scales of microseconds with more than 40% contrast between the resistance states. The latter are found to be nonvolatile for months. The switching could also be achieved at nanoscales with atomic force microscopy with a better resistance contrast of three orders of magnitude.
3-hydroxykynurenine suppresses CD4+ T-cell proliferation, induces T-regulatory-cell development, and prolongs corneal allograft survival
Copyright © 2011 Association for Research in Vision and Ophthalmology. This article is available open access through the publisher’s website at the link below.Purpose. IDO (indoleamine 2,3-dioxygenase) modulates the immune response by depletion of the essential amino acid tryptophan, and IDO overexpression has been shown to prolong corneal allograft survival. This study was conducted to examine the effect of kynurenines, the products of tryptophan breakdown and known to act directly on T lymphocytes, on corneal graft survival.
Methods. The effects of kynurenines on T-cell proliferation and death, T-regulatory-cell development, and dendritic cell function, phenotype, and viability were analyzed in vitro. The effect of topical and systemic administration of 3-hydroxykynurenine (3HK) on orthotopic murine corneal allograft survival was examined.
Results. T-lymphocyte proliferation was inhibited by two of the four different kynurenines: 3HK and 3-hydroxyanthranilic acid (3HAA). This effect was accompanied by significant T-cell death. Neither 3HK nor 3HAA altered dendritic cell function, nor did they induce apoptosis or pathogenicity to corneal endothelial cells. Administration of systemic and topical 3HK to mice receiving a fully mismatched corneal graft resulted in significant prolongation of graft survival (median survival of control grafts, 12 days; of treated, 19 and 15 days, respectively; P < 0.0003). While systemic administration of 3HK was associated with a significant depletion of CD4+ T, CD8+ T, and B lymphocytes in peripheral blood, no depletion was found after topical administration.
Conclusions. The production of kynurenines, in particular 3HK and 3HAA, may be one mechanism (in addition to tryptophan depletion) by which IDO prolongs graft survival. These molecules have potential as specific agents for preventing allograft rejection in patients at high rejection risk.Fight for Sight and the Wellcome Trust
G2A Attenuates Propionibacterium acnes Induction of Inflammatory Cytokines in Human Monocytes.
Background:Acne vulgaris is a disease of the pilosebaceous unit characterized by increased sebum production, hyperkeratinization, and immune responses to Propionibacterium acnes (PA). Here, we explore a possible mechanism by which a lipid receptor, G2A, regulates immune responses to a commensal bacterium. Objective:To elucidate the inflammatory properties of G2A in monocytes in response to PA stimulation. Furthermore, our study sought to investigate pathways by which lipids modulate immune responses in response to PA. Methods:Our studies focused on monocytes collected from human peripheral blood mononuclear cells, the monocytic cell line THP-1, and a lab strain of PA. Our studies involved the use of enzyme-linked immunosorbent, Western blot, reverse transcription polymerase chain reaction, small interfering RNA (siRNA), and microarray analysis of human acne lesions in the measurements of inflammatory markers. Results:G2A gene expression is higher in acne lesions compared to normal skin and is inducible by the acne therapeutic, 13-cis-retinoic acid. In vitro, PA induces both the Toll-like receptor 2-dependent expression of G2A as well as the production of the G2A ligand, 9-hydroxyoctadecadienoic acid, from human monocytes. G2A gene knockdown through siRNA enhances PA stimulation of interleukin (IL)-6, IL-8, and IL-1β possibly through increased activation of the ERK1/2 MAP kinase and nuclear factor kappa B p65 pathways. Conclusion:G2A may play a role in quelling inflammatory cytokine response to PA, revealing G2A as a potential attenuator of inflammatory response in a disease associated with a commensal bacterium
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Been around the block: Is the prior experience of coaches in the workplace helpful?
While most business coaches have prior experience of a workplace, there is debate as to how this should, or does, contribute to their coaching. It is often considered that coaches should be an expert in the process of coaching, and not their client’s business. This study utilised an inductive design to explore the perception of the contribution of prior work experience through semi-structured interviews with 11 clients and 13 experienced coaches. The interviews were analysed using reflexive thematic analysis. The data showed that both clients and coaches valued the coach having experience of working at a similar level. This helped establish credentials at the point of hiring, as well as providing authority and confidence during the coaching relationship. Such experience was also seen to give reference points and wisdom. However, while some participants saw advantages in the coach having a similar work background to the client (providing a common language and shared experiences), others considered that, while it was important that the coach had ‘been around the block’, this could be in a different work domain to the client. Clients also valued the wider experiences of a coach (such as artistic or socio-political) that brought creative insights and wider experiences
Serum vitamin D levels, diabetes and cardio-metabolic risk factors in Aboriginal and Torres Strait Islander Australians
Assesses levels of serum 25(OH)D in Aboriginal and Torres Strait Islander Australians and explores relationships between 25(OH)D and cardio-metabolic risk factors and diabetes.
Abstract
Background: Low levels of serum 25 – hydroxy vitamin D (25(OH)D), have been associated with development of type 2 diabetes and cardiovascular disease (CVD); however there are limited data on serum 25(OH)D in Indigenous Australians, a population at high risk for both diabetes and CVD. We aimed to assess levels of serum 25(OH)D in Aboriginal and Torres Strait Islander Australians and to explore relationships between 25(OH)D and cardio-metabolic risk factors and diabetes.
Methods: 592 Aboriginal and/or Torres Strait Islander Australian participants of The eGFR (estimated glomerular filtration rate) Study, a cross-sectional analysis of a cohort study performed in 2007 – 2011, from urban and remote centres within communities, primary care and tertiary hospitals across Northern Territory, Far North Queensland and Western Australia. Assessment of serum 25(OH)D, cardio-metabolic risk factors (central obesity, diabetes, hypertension, history of cardiovascular disease, current smoker, low HDL-cholesterol), and diabetes (by history or HbA1c ≥ 6.5%) was performed. Associations were explored between 25(OH)D and outcome measures of diabetes and number of cardio-metabolic risk factors.
Results: The median (IQR) serum 25(OH)D was 60 (45 – 77) nmol/L, 31% had 25(OH)D <50 nmol/L. For participants with 25(OH)D < 50 vs ≥ 50 nmol/L, cardio-metabolic risk profile differed for: diabetes (54%, 36% p < 0.001), past history of cardiovascular disease (16%, 9%, p = 0.014), waist-hip ratio (0.98, 0.92, p < 0.001), urine albumin-creatinine ratio (2.7, 1.5 mg/mmol, p < 0.001). The OR (95% CI) for diabetes was 2.02 (1.03 – 3.95) for people in the lowest vs highest tertiles of 25(OH)D (<53 vs >72 nmol/L, respectively) after adjusting for known cardio-metabolic risk factors.
Conclusion: The percentage of 25(OH)D levels <50 nmol/L was high among Aboriginal and Torres Strait Islander Australians from Northern and Central Australia. Low 25(OH)D level was associated with adverse cardio-metabolic risk profile and was independently associated with diabetes. These findings require exploration in longitudinal studies
Medieval Iceland, Greenland, and the New Human Condition: A case study in integrated environmental humanities
This paper contributes to recent studies exploring the longue durée of human impacts on island landscapes, the impacts of climate and other environmental changes on human communities, and the interaction of human societies and their environments at different spatial and temporal scales. In particular, the paper addresses Iceland during the medieval period (with a secondary, comparative focus on Norse Greenland) and discusses episodes where environmental and climatic changes have appeared to cross key thresholds for agricultural productivity. The paper draws upon international, interdisciplinary research in the North Atlantic region led by the North Atlantic Biocultural Organization (NABO) and the Nordic Network for Interdisciplinary Environmental Studies (NIES) in the Circumpolar Networks program of the Integrated History and Future of People on Earth (IHOPE). By interlinking analyses of historically grounded literature with archaeological studies and environmental science, valuable new perspectives can emerge on how these past societies may have understood and coped with such impacts. As climate and other environmental changes do not operate in isolation, vulnerabilities created by socioeconomic factors also beg consideration. The paper illustrates the benefits of an integrated environmental-studies approach that draws on data, methodologies and analytical tools of environmental humanities, social sciences, and geosciences to better understand long-term human ecodynamics and changing human-landscape-environment interactions through time. One key goal is to apply previously unused data and concerted expertise to illuminate human responses to past changes; a secondary aim is to consider how lessons derived from these cases may be applicable to environmental threats and socioecological risks in the future, especially as understood in light of the New Human Condition, the concept transposed from Hannah Arendt's influential framing of the human condition that is foregrounded in the present special issue. This conception admits human agency's role in altering the conditions for life on earth, in large measure negatively, while acknowledging the potential of this self-same agency, if effectively harnessed and properly directed, to sustain essential planetary conditions through a salutary transformation of human perception, understanding and remedial action. The paper concludes that more long-term historical analyses of cultures and environments need to be undertaken at various scales. Past cases do not offer perfect analogues for the future, but they can contribute to a better understanding of how resilience and vulnerability occur, as well as how they may be compromised or mitigated
Exploring the Optical Transient Sky with the Palomar Transient Factory
The Palomar Transient Factory (PTF) is a wide-field experiment designed to
investigate the optical transient and variable sky on time scales from minutes
to years. PTF uses the CFH12k mosaic camera, with a field of view of 7.9 deg^2
and a plate scale of 1 asec/pixel, mounted on the the Palomar Observatory
48-inch Samuel Oschin Telescope. The PTF operation strategy is devised to probe
the existing gaps in the transient phase space and to search for theoretically
predicted, but not yet detected, phenomena, such as fallback supernovae,
macronovae, .Ia supernovae and the orphan afterglows of gamma-ray bursts. PTF
will also discover many new members of known source classes, from cataclysmic
variables in their various avatars to supernovae and active galactic nuclei,
and will provide important insights into understanding galactic dynamics
(through RR Lyrae stars) and the Solar system (asteroids and near-Earth
objects). The lessons that can be learned from PTF will be essential for the
preparation of future large synoptic sky surveys like the Large Synoptic Survey
Telescope. In this paper we present the scientific motivation for PTF and
describe in detail the goals and expectations for this experiment.Comment: 15 pages, 6 figures, submitted to PAS
Predicting blunt cerebrovascular injury in pediatric trauma: Validation of the Utah Score
Risk factors for blunt cerebrovascular injury (BCVI) may differ between children and adults, suggesting that children at low risk for BCVI after trauma receive unnecessary computed tomography angiography (CTA) and high-dose radiation. We previously developed a score for predicting pediatric BCVI based on retrospective cohort analysis. Our objective is to externally validate this prediction score with a retrospective multi-institutional cohort. We included patients who underwent CTA for traumatic cranial injury at four pediatric Level I trauma centers. Each patient in the validation cohort was scored using the “Utah Score” and classified as high or low risk. Before analysis, we defined a misclassification rate <25% as validating the Utah Score. Six hundred forty-five patients (mean age 8.6 ± 5.4 years; 63.4% males) underwent screening for BCVI via CTA. The validation cohort was 411 patients from three sites compared with the training cohort of 234 patients. Twenty-two BCVIs (5.4%) were identified in the validation cohort. The Utah Score was significantly associated with BCVIs in the validation cohort (odds ratio 8.1 [3.3, 19.8], p < 0.001) and discriminated well in the validation cohort (area under the curve 72%). When the Utah Score was applied to the validation cohort, the sensitivity was 59%, specificity was 85%, positive predictive value was 18%, and negative predictive value was 97%. The Utah Score misclassified 16.6% of patients in the validation cohort. The Utah Score for predicting BCVI in pediatric trauma patients was validated with a low misclassification rate using a large, independent, multicenter cohort. Its implementation in the clinical setting may reduce the use of CTA in low-risk patients
A complete view of galaxy evolution: panchromatic luminosity functions and the generation of metals
When and how did galaxies form and their metals accumulate? Over the last
decade, this has moved from an archeological question to a live investigation:
there is now a broad picture of the evolution of galaxies in dark matter halos:
their masses, stars, metals and supermassive blackholes. Galaxies have been
found and studied in which these formation processes are taking place most
vigorously, all the way back in cosmic time to when the intergalactic medium
(IGM) was still largely neutral. However, the details of how and why the
interstellar medium (ISM) in distant galaxies cools, is processed, recycled and
enriched in metals by stars, and fuels active galactic nuclei (AGNs) remain
uncertain. In particular, the cooling of gas to fuel star formation, and the
chemistry and physics of the most intensely active regions is hidden from view
at optical wavelengths, but can be seen and diagnosed at mid- & far-infrared
(IR) wavelengths. Rest-frame IR observations are important first to identify
the most luminous, interesting and important galaxies, secondly to quantify
accurately their total luminosity, and finally to use spectroscopy to trace the
conditions in the molecular and atomic gas out of which stars form. In order to
map out these processes over the full range of environments and large-scale
structures found in the universe - from the densest clusters of galaxies to the
emptiest voids - we require tools for deep, large area surveys, of millions of
galaxies out to z~5, and for detailed follow-up spectroscopy. The necessary
tools can be realized technically. Here, we outline the requirements for
gathering the crucial information to build, validate and challenge models of
galaxy evolution.Comment: A whitepaper submitted on 15th February 2009 in response to the call
from the Astro2010 panel: astro2010.org; uploaded as an 8-page pdf fil
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