358 research outputs found

    The lithium depletion boundary and the age of NGC 2547

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    We present the results of a photometric and spectroscopic survey of cool M dwarf candidates in the young open cluster NGC 2547. Using the 2dF fiber spectrograph, we have searched for the luminosity at which lithium remains unburned in an attempt to constrain the cluster age. The lack of a population of individual lithium-rich objects towards the faint end of our sample places a very strong lower limit to the cluster age of 35 Myr. However, the detection of lithium in the averaged spectra of our faintest targets suggests that the lithium depletion boundary lies at 9.5 < M(I) < 10.0 and that the cluster age is < 54 Myr. The age of NGC 2547 judged from fitting isochrones to low-mass pre-main-sequence stars in colour-magnitude diagrams is 20-35 Myr using the same evolutionary models. The sense and size of the discrepancy in age determined by these two techniques is similar to that found in another young cluster, IC 2391, and in the low-mass pre main-sequence binary system, GJ 871.1AB. We suggest that the inclusion of rotation or dynamo-generated magnetic fields in the evolutionary models could reconcile the two age determinations, but only at the expense of increasing the cluster ages beyond that currently indicated by the lithium depletion. Alternatively, some mechanism is required that increases the rate of lithium depletion in young, very low-mass fully convective stars.Comment: 14 pages, 7 figures, 3 tables, accepted by MNRA

    Ischemic preconditioning in the liver is independent of regulatory T cell activity

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    Ischemic preconditioning (IPC) protects organs from ischemia reperfusion injury (IRI) through unknown mechanisms. Effector T cell populations have been implicated in the pathogenesis of IRI, and T regulatory cells (Treg) have become a putative therapeutic target, with suggested involvement in IPC. We explored the role of Treg in hepatic IRI and IPC in detail. IPC significantly reduced injury following ischemia reperfusion insults. Treg were mobilized rapidly to the circulation and liver after IRI, but IPC did not further increase Treg numbers, nor was it associated with modulation of circulating pro-inflammatory chemokine or cytokine profiles. We used two techniques to deplete Treg from mice prior to IRI. Neither Treg depleted FoxP3.LuciDTR mice, nor wildtyoe mice depleted of Tregs with PC61, were more susceptible to IRI compared with controls. Despite successful enrichment of Treg in the liver, by adoptive transfer of both iTreg and nTreg or by in vivo expansion of Treg with IL-2/anti-IL-2 complexes, no protection against IRI was observed.We have explored the role of Treg in IRI and IPC using a variety of techniques to deplete and enrich them within both the liver and systemically. This work represents an important negative finding that Treg are not implicated in IPC and are unlikely to have translational potential in hepatic IRI

    A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function.

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    INTRODUCTION: Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation. METHODS: The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers. RESULTS: GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ-induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs. CONCLUSION: Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population. TRIAL REGISTRATION: NCT02723786

    The Great Separation: Top Earner Segregation at Work in High-Income Countries

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    Analyzing linked employer-employee panel administrative databases, we study the evolving isolation of higher earners from other employees in eleven countries: Canada, Czechia, Denmark, France, Germany, Hungary, Japan, Norway, Spain, South Korea, and Sweden. We find in almost all countries a growing workplace isolation of top earners and dramatically declining exposure of top earners to bottom earners. We compare these trends to segregation based on occupational class, education, age, gender, and nativity, finding that the rise in top earner isolation is much more dramatic and general across countries. We find that residential segregation is also growing, although more slowly than segregation at work, with top earners and bottom earners increasingly living in different distinct municipalities. While work and residential segregation are correlated, statistical modeling suggests that the primary causal effect is from work to residential segregation. These findings open up a future research program on the causes and consequences of top earner segregation.En nous appuyant sur des données administratives longitudinales employeur–employés, nous analysons l’évolution de la ségrégation sociale des salariés à hauts salaires dans onze pays: Allemagne, Canada, Corée du Sud, Danemark, Espagne, France, Hongrie, Japon, Norvège, République tchèque et Suède. Nous constatons dans presque tous les pays une forte augmentation de l’entre soi des salariés bien payés sur le lieu de travail et une diminution spectaculaire de leur exposition aux bas salaires. Nous comparons ces tendances à l’évolution de la ségrégation fondée sur la catégorie sociale, l’éducation, l’âge, le sexe et le statut migratoire, et nous constatons que l’augmentation de l’entre soi des hauts salaires est celle qui est la plus prononcée et la plus générale. Nous montrons que la ségrégation résidentielle se développe aussi, bien que plus lentement que la ségrégation au travail, avec les hauts et les bas salaires vivant de plus en plus dans des municipalités distinctes. Ségrégation au travail et ségrégation résidentielle sont corrélées. Mais nos modèles statistiques suggèrent aussi que la principale relation de causalité va de la ségrégation au travail vers la ségrégation résidentielle. Ces résultats ouvrent la voie à un futur programme de recherche sur les causes et les conséquences de la ségrégation des hauts salaires.1 Introduction 2 From ethnic residential segregation to earnings segregation at work 3 Administrative data for estimating exposure measures 4 A strong increase in earnings segregation at work 5 A robust trend 17 French robustness tests 6 A specific trend 7 The link between work and residential segregation 8 Elements for a research program on the causes and consequences of increasing segregation at work The roots of growing earnings segregation at work The consequences of growing earnings segregation at work Appendices A1 Data sources and sample definition A2 Demonstration of the symmetry of relative exposure gRh = hRg A3 Figure construction A4 French robustness checks Supplementary figures and tables Reference

    New Insights into the mineralogy of the Atlantis II deep metalliferous sediments, Red Sea

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    The Atlantis II Deep of the Red Sea hosts the largest known hydrothermal ore deposit on the ocean floor and the only modern analog of brine pool-type metal deposition. The deposit consists mainly of chemical-clastic sediments with input from basin-scale hydrothermal and detrital sources. A characteristic feature is the millimeter-scale layering of the sediments, which bears a strong resemblance to banded iron formation (BIF). Quantitative assessment of the mineralogy based on relogging of archived cores, detailed petrography, and sequential leaching experiments shows that Fe-(oxy)hydroxides, hydrothermal carbonates, sulfides, and authigenic clays are the main “ore” minerals. Mn-oxides were mainly deposited when the brine pool was more oxidized than it is today, but detailed logging shows that Fe-deposition and Mn-deposition also alternated at the scale of individual laminae, reflecting short-term fluctuations in the Lower Brine. Previous studies underestimated the importance of nonsulfide metal-bearing components, which formed by metal adsorption onto poorly crystalline Si-Fe-OOH particles. During diagenesis, the crystallinity of all phases increased, and the fine layering of the sediment was enhanced. Within a few meters of burial (corresponding to a few thousand years of deposition), biogenic (Ca)-carbonate was dissolved, manganosiderite formed, and metals originally in poorly crystalline phases or in pore water were incorporated into diagenetic sulfides, clays, and Fe-oxides. Permeable layers with abundant radiolarian tests were the focus for late-stage hydrothermal alteration and replacement, including deposition of amorphous silica and enrichment in elements such as Ba and Au

    Tectonic and magmatic controls on hydrothermal activity in the Woodlark Basin

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    The Woodlark Basin is one of the rare places on earth where the transition from continental breakup to seafloor spreading can be observed. The potential juxtaposition of continental rocks, a large magmatic heat source, crustal-scale faulting, and hydrothermal circulation has made the Woodlark Basin a prime target for seafloor mineral exploration. However, over the past 20 years, only two locations of active hydrothermalism had been found. In 2009 we surveyed 435 km of the spreading axis for the presence of hydrothermal plumes. Only one additional plume was found, bringing the total number of plumes known over 520 km of ridge axis to only 3, much less than at ridges with similar spreading rates globally. Particularly the western half of the basin (280 km of axis) is apparently devoid of high temperature plumes despite having thick crust and a presumably high magmatic budget. This paucity of hydrothermal activity may be related to the peculiar tectonic setting at Woodlark, where repeated ridge jumps and a re-location of the rotation pole both lead to axial magmatism being more widely distributed than at many other, more mature and stable mid-ocean ridges. These factors could inhibit the development of both a stable magmatic heat source and the deeply penetrating faults needed to create long-lived hydrothermal systems. We conclude that large seafloor massive sulfide deposits, potential targets for seafloor mineral exploration, will probably not be present along the spreading axis of the Woodlark Basin, especially in its younger, western portion

    Introductory programming: a systematic literature review

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    As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research

    Missing Links: Referrer Behavior and Job Segregation

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    How does referral recruitment contribute to job segregation, and what can organizations do about it? Current theory on network effects in the labor market emphasizes the job-seeker perspective, focusing on the segregated nature of job-seekers’ information and contact networks, and leaves little role for organizational influence. But employee referrals are necessarily initiated from within a firm by referrers. We argue that referrer behavior is the missing link that can help organizations manage the segregating effects of referring. Adopting the referrer’s perspective of the process, we develop a computational model which integrates a set of empirically documented referrer behavior mechanisms gleaned from extant organizational case studies. Using this model, we compare the segregating effects of referring when these behaviors are inactive to the effects when the behaviors are active. We show that referrer behaviors substantially boost the segregating effects of referring. This impact of referrer behavior presents an opportunity for organizations. Contrary to popular wisdom, we show that organizational policies designed to influence referrer behaviors can mitigate most if not all of the segregating effects of referring
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