275 research outputs found

    Background-free detection of trapped ions

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    We demonstrate a Doppler cooling and detection scheme for ions with low-lying D levels which almost entirely suppresses scattered laser light background, while retaining a high fluorescence signal and efficient cooling. We cool a single ion with a laser on the 2S1/2 to 2P1/2 transition as usual, but repump via the 2P3/2 level. By filtering out light on the cooling transition and detecting only the fluorescence from the 2P_3/2 to 2S1/2 decays, we suppress the scattered laser light background count rate to 1 per second while maintaining a signal of 29000 per second with moderate saturation of the cooling transition. This scheme will be particularly useful for experiments where ions are trapped in close proximity to surfaces, such as the trap electrodes in microfabricated ion traps, which leads to high background scatter from the cooling beam

    Heating rate and electrode charging measurements in a scalable, microfabricated, surface-electrode ion trap

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    We characterise the performance of a surface-electrode ion "chip" trap fabricated using established semiconductor integrated circuit and micro-electro-mechanical-system (MEMS) microfabrication processes which are in principle scalable to much larger ion trap arrays, as proposed for implementing ion trap quantum information processing. We measure rf ion micromotion parallel and perpendicular to the plane of the trap electrodes, and find that on-package capacitors reduce this to <~ 10 nm in amplitude. We also measure ion trapping lifetime, charging effects due to laser light incident on the trap electrodes, and the heating rate for a single trapped ion. The performance of this trap is found to be comparable with others of the same size scale.Comment: 6 pages, 10 figure

    Interpreting an apoptotic corpse as anti-inflammatory involves a chloride sensing pathway

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    Apoptotic cell clearance (efferocytosis) elicits an anti-inflammatory response by phagocytes, but the mechanisms that underlie this response are still being defined. Here, we uncover a chloride-sensing signalling pathway that controls both the phagocyte 'appetite' and its anti-inflammatory response. Efferocytosis transcriptionally altered the genes that encode the solute carrier (SLC) proteins SLC12A2 and SLC12A4. Interfering with SLC12A2 expression or function resulted in a significant increase in apoptotic corpse uptake per phagocyte, whereas the loss of SLC12A4 inhibited corpse uptake. In SLC12A2-deficient phagocytes, the canonical anti-inflammatory program was replaced by pro-inflammatory and oxidative-stress-associated gene programs. This 'switch' to pro-inflammatory sensing of apoptotic cells resulted from the disruption of the chloride-sensing pathway (and not due to corpse overload or poor degradation), including the chloride-sensing kinases WNK1, OSR1 and SPAK-which function upstream of SLC12A2-had a similar effect on efferocytosis. Collectively, the WNK1-OSR1-SPAK-SLC12A2/SLC12A4 chloride-sensing pathway and chloride flux in phagocytes are key modifiers of the manner in which phagocytes interpret the engulfed apoptotic corpse

    Pannexin 1 drives efficient epithelial repair after tissue injury

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    Epithelial tissues such as lung and skin are exposed to the environment and therefore particularly vulnerable to damage during injury or infection. Rapid repair is therefore essential to restore function and organ homeostasis. Dysregulated epithelial tissue repair occurs in several human disease states, yet how individual cell types communicate and interact to coordinate tissue regeneration is incompletely understood. Here, we show that pannexin 1 (Panx1), a cell membrane channel activated by caspases in dying cells, drives efficient epithelial regeneration after tissue injury by regulating injury-induced epithelial proliferation. Lung airway epithelial injury promotes the Panx1-dependent release of factors including ATP, from dying epithelial cells, which regulates macrophage phenotype after injury. This process, in turn, induces a reparative response in tissue macrophages that includes the induction of the soluble mitogen amphiregulin, which promotes injury-induced epithelial proliferation. Analysis of regenerating lung epithelium identified Panx1-dependent induction of Nras and Bcas2, both of which positively promoted epithelial proliferation and tissue regeneration in vivo. We also established that this role of Panx1 in boosting epithelial repair after injury is conserved between mouse lung and zebrafish tailfin. These data identify a Panx1-mediated communication circuit between epithelial cells and macrophages as a key step in promoting epithelial regeneration after injury

    Phagocytosis in the retina promotes local insulin production in the eye

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    The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors (‘loss of function’) reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK (‘gain of function’) increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease

    Helminths and HIV infection: epidemiological observations on immunological hypotheses

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    Parasitic helminths have co-evolved with the mammalian immune system. Current hypotheses suggest that immunological stimulation in the presence of helminths is balanced by immuno-regulation and by the broad spectrum of mechanisms possessed by helminths for countering the host immune response. The degree to which this balance is perfected, and the mechanisms by which this is achieved, vary between helminth species; we suggest that this is reflected not only in the degree of pathology induced by helminths but also in a variety of relationships with HIV infection and HIV disease. Available epidemiological data regarding interactions between helminths and HIV are largely observational; results are variable and generally inconclusive. Well designed, controlled intervention studies are required to provide definitive information on the species-specific nature of these interactions and on the advantages, disadvantages and optimal timing of de-worming in relation to HIV infection

    An exploration into the impact of exposure to community violence and hope on children's perceptions of well-being: a South African perspective

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    The study aims to explore the relationship between exposure to community violence, hope, and well-being. More specifically, the study aims to ascertain whether hope is a stronger predictor of well-being than exposure to violence. Stratified random sampling was used to select a sample of 566 adolescents aged 14–17 years, from both high violence and low violence areas in Cape Town, South Africa. A questionnaire consisting of Snyder’s Children’s Hope Scale, the Recent Exposure to Violence Scale and the KIDSCREEN-52 was used. Data analysis techniques included descriptive statistics, correlations, and multiple regression. A positive, significant relationship was found between children’s hope and their well-being. Although exposure to community violence was found to be significantly correlated with wellbeing, the relationship was negligible.While exposure to community violence and hope were found to be significant predictors of well-being, hope emerged as a stronger predictor of child well-being than exposure to community violence.Department of HE and Training approved lis

    Crowdsourcing hypothesis tests: making transparent how design choices shape research results

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    To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer five original research questions related to moral judgments, negotiations, and implicit cognition. Participants from 2 separate large samples (total N > 15,000) were then randomly assigned to complete 1 version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: Materials from different teams rendered statistically significant effects in opposite directions for 4 of 5 hypotheses, with the narrowest range in estimates being d = -0.37 to + 0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for 2 hypotheses and a lack of support for 3 hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, whereas considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.info:eu-repo/semantics/submittedVersio
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