1,507 research outputs found

    Laser-heated capillary discharge plasma waveguides for electron acceleration to 8 GeV

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    A plasma channel created by the combination of a capillary discharge and inverse Bremsstrahlung laser heating enabled the generation of electron bunches with energy up to 7.8 GeV in a laser-driven plasma accelerator. The capillary discharge created an initial plasma channel and was used to tune the plasma temperature, which optimized laser heating. Although optimized colder initial plasma temperatures reduced the ionization degree, subsequent ionization from the heater pulse created a fully ionized plasma on-axis. The heater pulse duration was chosen to be longer than the hydrodynamic timescale of ≈ 1 ns, such that later temporal slices were more efficiently guided by the channel created by the front of the pulse. Simulations are presented which show that this thermal self-guiding of the heater pulse enabled channel formation over 20 cm. The post-heated channel had lower on-axis density and increased focusing strength compared to relying on the discharge alone, which allowed for guiding of relativistically intense laser pulses with a peak power of 0.85 PW and wakefield acceleration over 15 diffraction lengths. Electrons were injected into the wake in multiple buckets and times, leading to several electron bunches with different peak energies. To create single electron bunches with low energy spread, experiments using localized ionization injection inside a capillary discharge waveguide were performed. A single injected bunch with energy 1.6 GeV, charge 38 pC, divergence 1 mrad, and relative energy spread below 2% full-width half-maximum was produced in a 3.3 cm-long capillary discharge waveguide. This development shows promise for mitigation of energy spread and future high efficiency staged acceleration experiments

    Observation of interstellar lithium in the low-metallicity Small Magellanic Cloud

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    The primordial abundances of light elements produced in the standard theory of Big Bang nucleosynthesis (BBN) depend only on the cosmic ratio of baryons to photons, a quantity inferred from observations of the microwave background. The predicted primordial 7Li abundance is four times that measured in the atmospheres of Galactic halo stars. This discrepancy could be caused by modification of surface lithium abundances during the stars' lifetimes or by physics beyond the Standard Model that affects early nucleosynthesis. The lithium abundance of low-metallicity gas provides an alternative constraint on the primordial abundance and cosmic evolution of lithium that is not susceptible to the in situ modifications that may affect stellar atmospheres. Here we report observations of interstellar 7Li in the low-metallicity gas of the Small Magellanic Cloud, a nearby galaxy with a quarter the Sun's metallicity. The present-day 7Li abundance of the Small Magellanic Cloud is nearly equal to the BBN predictions, severely constraining the amount of possible subsequent enrichment of the gas by stellar and cosmic-ray nucleosynthesis. Our measurements can be reconciled with standard BBN with an extremely fine-tuned depletion of stellar Li with metallicity. They are also consistent with non-standard BBN.Comment: Published in Nature. Includes main text and Supplementary Information. Replaced with final title and abstrac

    Silencing cortical activity during sound-localization training impairs auditory perceptual learning

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    The brain has a remarkable capacity to adapt to changes in sensory inputs and to learn from experience. However, the neural circuits responsible for this flexible processing remain poorly understood. Using optogenetic silencing of ArchT-expressing neurons in adult ferrets, we show that within-trial activity in primary auditory cortex (A1) is required for training-dependent recovery in sound-localization accuracy following monaural deprivation. Because localization accuracy under normal-hearing conditions was unaffected, this highlights a specific role for cortical activity in learning. A1-dependent plasticity appears to leave a memory trace that can be retrieved, facilitating adaptation during a second period of monaural deprivation. However, in ferrets in which learning was initially disrupted by perturbing A1 activity, subsequent optogenetic suppression during training no longer affected localization accuracy when one ear was occluded. After the initial learning phase, the reweighting of spatial cues that primarily underpins this plasticity may therefore occur in A1 target neurons

    Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

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    Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB

    Single Nucleotide Polymorphisms in IL1B and the Risk of Acute Coronary Syndrome: A Danish Case-Cohort Study

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    BACKGROUND: Interleukin-1B (IL-1B) is a key pro-inflammatory cytokine that has been associated with the development of atherosclerosis and myocardial infarction. However, the prospective associations between functional single nucleotide polymorphisms (SNPs) in IL1B and incident acute coronary syndrome (ACS) have not been thoroughly investigated. The aims of this study were to examine the associations between individual SNPs in and SNP haplotypes of the promoter region of IL1B and incident ACS in a prospective study. Furthermore, we wanted to explore potential interactions with other risk factors for ACS on an additive scale. METHODOLOGY/PRINCIPAL FINDINGS: The present study was based on the Danish prospective study Diet, Cancer and Health comprising more than 57 000 participants aged 50-64 at baseline. During a median follow-up of 7.2 years we identified 989 cases of incident ACS (755 men and 234 women). All cases were validated by review of medical records, and information on covariates was collected by study technicians. The study was conducted according to a case-cohort study design including ACS cases and a sex-stratified sub cohort of 1663 participants drawn randomly from the entire cohort. Weighted Cox proportional hazard models with age as time axis were used in the statistical analyses. Individual IL1B SNPs, SNP haplotypes, or haplotype combinations were not significantly associated with incident ACS, and, likewise, we found no evidence of interaction on an additive scale between IL1B haplotypes and risk factors, respectively. CONCLUSIONS/SIGNIFICANCE: Genetic variation in the promoter region of IL1B may not be associated with incident ACS in men or women above the age of 50 years

    Boerhaave syndrome as a complication of colonoscopy preparation: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Colonoscopy is one of the most frequently performed elective and invasive diagnostic interventions. For every colonoscopy, complete colon preparation is mandatory to provide the best possible endoluminal visibility; for example, the patient has to drink a great volume of a non-resorbable solution to flush out all feces. Despite the known possible nauseating side effects of colonoscopy preparation and despite the knowledge that excessive vomiting can cause rupture of the distal esophagus (Boerhaave syndrome), which is a rare but severe complication with high morbidity and mortality, it is not yet a standard procedure to provide a patient with an anti-emetic medication during a colon preparation process. This is the first report of Boerhaave syndrome induced by colonoscopy preparation, and this case strongly suggests that the prospect of being at risk of a severe complication connected with an elective colonoscopy justifies a non-invasive, inexpensive yet effective precaution such as an anti-emetic co-medication during the colonoscopy preparation process.</p> <p>Case presentation</p> <p>A 73-year-old Caucasian woman was scheduled to undergo elective colonoscopy. For the colonoscopy preparation at home she received commercially available bags containing soluble polyethylene glycol powder. No anti-emetic medication was prescribed. After drinking the prepared solution she had to vomit excessively and experienced a sudden and intense pain in her back. An immediate computed tomography (CT) scan revealed a rupture of the distal esophagus (Boerhaave syndrome). After initial conservative treatment by endoluminal sponge vacuum therapy, she was taken to the operating theatre and the longitudinal esophageal rupture was closed by direct suture and gastric fundoplication (Nissen procedure). She recovered completely and was discharged three weeks after the initial event.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first report of a case of Boerhaave syndrome as a complication of excessive vomiting caused by colonoscopy preparation. The case suggests that patients who are prepared for a colonoscopy by drinking large volumes of fluid should routinely receive an anti-emetic medication during the preparation process, especially when they have a tendency to nausea and vomiting.</p

    A probable stellar solution to the cosmological lithium discrepancy

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    The measurement of the cosmic microwave background has strongly constrained the cosmological parameters of the Universe. When the measured density of baryons (ordinary matter) is combined with standard Big Bang nucleosynthesis calculations, the amounts of hydrogen, helium and lithium produced shortly after the Big Bang can be predicted with unprecedented precision. The predicted primordial lithium abundance is a factor of two to three higher than the value measured in the atmospheres of old stars. With estimated errors of 10 to 25%, this cosmological lithium discrepancy seriously challenges our understanding of stellar physics, Big Bang nucleosynthesis or both. Certain modifications to nucleosynthesis have been proposed, but found experimentally not to be viable. Diffusion theory, however, predicts atmospheric abundances of stars to vary with time, which offers a possible explanation of the discrepancy. Here we report spectroscopic observations of stars in the metalpoor globular cluster NGC 6397 that reveal trends of atmospheric abundance with evolutionary stage for various elements. These element-specific trends are reproduced by stellar-evolution models with diffusion and turbulent mixing. We thus conclude that diffusion is predominantly responsible for the low apparent stellar lithium abundance in the atmospheres of old stars by transporting the lithium deep into the star.Comment: 10 pages, 3 two-panel figures, 2 tables, includes all Supplementary Information otherwise accessible online via www.nature.co

    Apolipoprotein E gene is related to mortality only in normal weight individuals: The Rotterdam study

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    Objective To investigate the relationship between the apolipoprotein E (APOE) gene and the risk of mortality in normal weight, overweight and obese individuals. Methods and Results In a population-based study of 7,983 individuals aged 55 years and older, we compared the risks of all-cause and coronary heart disease (CHD) mortality by APOE genotype, both overall and in subgroups defined by body mass index (BMI). We found significant evidence for interaction between APOE and BMI in relation to total cholesterol (p = 0.04) and HDL cholesterol (p < 0.001). Overall, APOE*2 carriers showed a decreased risk of all-cause mortality. Analyses within BMI strata showed a beneficial effect of APOE*2 only in normal weight persons (adjusted hazard ratio (HR) 0.7[95% CI 0.5–0.9]). APOE*2 was not associated with a lower risk of all-cause mortality in overweight or obese persons. The effect of APOE*2 in normal weight individuals tended to be due to the risk of CHD mortality (adjusted HR 0.5 [95% CI 0.2–1.2]). Conclusion The APOE*2 allele confers a lower risk of all-cause mortality only to normal weight individuals
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