Chronic obstructive pulmonary disease (COPD) is defined by the presence of airflow limitation on spirometry, yet subjects with COPD can have marked differences in computed tomography imaging. These ...differences may be driven by genetic factors. We hypothesized that a genome-wide association study (GWAS) of quantitative imaging would identify loci not previously identified in analyses of COPD or spirometry. In addition, we sought to determine whether previously described genome-wide significant COPD and spirometric loci were associated with emphysema or airway phenotypes.
To identify genetic determinants of quantitative imaging phenotypes.
We performed a GWAS on two quantitative emphysema and two quantitative airway imaging phenotypes in the COPDGene (non-Hispanic white and African American), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), NETT (National Emphysema Treatment Trial), and GenKOLS (Genetics of COPD, Norway) studies and on percentage gas trapping in COPDGene. We also examined specific loci reported as genome-wide significant for spirometric phenotypes related to airflow limitation or COPD.
The total sample size across all cohorts was 12,031, of whom 9,338 were from COPDGene. We identified five loci associated with emphysema-related phenotypes, one with airway-related phenotypes, and two with gas trapping. These loci included previously reported associations, including the HHIP, 15q25, and AGER loci, as well as novel associations near SERPINA10 and DLC1. All previously reported COPD and a significant number of spirometric GWAS loci were at least nominally (P < 0.05) associated with either emphysema or airway phenotypes.
Genome-wide analysis may identify novel risk factors for quantitative imaging characteristics in COPD and also identify imaging features associated with previously identified lung function loci.
Observations of magnetic reconnection at Earth's magnetopause often display asymmetric structures that are accompanied by strong magnetic field (B) fluctuations and large‐amplitude parallel electric ...fields (E||). The B turbulence is most intense at frequencies above the ion cyclotron frequency and below the lower hybrid frequency. The B fluctuations are consistent with a thin, oscillating current sheet that is corrugated along the electron flow direction (along the X line), which is a type of electromagnetic drift wave. Near the X line, electron flow is primarily due to a Hall electric field, which diverts ion flow in asymmetric reconnection and accompanies the instability. Importantly, the drift waves appear to drive strong parallel currents which, in turn, generate large‐amplitude (~100 mV/m) E|| in the form of nonlinear waves and structures. These observations suggest that turbulence may be common in asymmetric reconnection, penetrate into the electron diffusion region, and possibly influence the magnetic reconnection process.
Key Points
Asymmetric magnetic reconnection at the magnetopause often has strong magnetic field fluctuations and intense parallel electric fields
The magnetic field fluctuations are consistent with a thin, oscillating current sheet that is corrugated along the X line (drift wave)
The drift waves appear to drive strong parallel currents which, in turn, generate large‐amplitude parallel electric fields
The Kelvin-Helmholtz (ICH) instability at the Earth's magnetopause is predominantly excited during northward interplanetary magnetic field (IMF). Magnetic reconnection due to KH waves has been ...suggested as one of the mechanisms to transfer solar wind plasma into the magnetosphere. We investigate KH waves observed at the magnetopause by the Magnetospheric Multlscale (MMS) mission; in particular, we study the trailing edges of KH waves with Alfvenic ion jets. We observe gradual mixing of magnetospheric and magnetosheath ions at the boundary layer. The magnetospheric electrons with energy up to 80 keV are observed on the magnetosheath side of the jets, which indicates that they escape into the magnetosheath through reconnected magnetic field lines. At the same time, the low-energy (below 100eV) magnetosheath electrons enter the magnetosphere and are heated in the field-aligned direction at the high-density edge of the jets. Our observations provide unambiguous kinetic evidence for ongoing reconnection due to KH waves.
Abstract
We introduce the Automatic Learning for the Rapid Classification of Events (ALeRCE) broker, an astronomical alert broker designed to provide a rapid and self-consistent classification of ...large etendue telescope alert streams, such as that provided by the Zwicky Transient Facility (ZTF) and, in the future, the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST). ALeRCE is a Chilean-led broker run by an interdisciplinary team of astronomers and engineers working to become intermediaries between survey and follow-up facilities. ALeRCE uses a pipeline that includes the real-time ingestion, aggregation, cross-matching, machine-learning (ML) classification, and visualization of the ZTF alert stream. We use two classifiers: a stamp-based classifier, designed for rapid classification, and a light curve–based classifier, which uses the multiband flux evolution to achieve a more refined classification. We describe in detail our pipeline, data products, tools, and services, which are made public for the community (see
https://alerce.science
). Since we began operating our real-time ML classification of the ZTF alert stream in early 2019, we have grown a large community of active users around the globe. We describe our results to date, including the real-time processing of 1.5 × 10
8
alerts, the stamp classification of 3.4 × 10
7
objects, the light-curve classification of 1.1 × 10
6
objects, the report of 6162 supernova candidates, and different experiments using LSST-like alert streams. Finally, we discuss the challenges ahead in going from a single stream of alerts such as ZTF to a multistream ecosystem dominated by LSST.
Afferent activity can induce fast, feed-forward changes in synaptic efficacy that are synapse specific. Using combined electrophysiology, caged molecule photolysis, and Ca
2+ imaging, we describe a ...plasticity in which the recruitment of astrocytes in response to afferent activity causes a fast and feed-forward, yet distributed increase in the amplitude of quantal synaptic currents at multiple glutamate synapses on magnocellular neurosecretory cells in the hypothalamic paraventricular nucleus. The plasticity is largely multiplicative, consistent with a proportional increase or “scaling” in the strength of all synapses on the neuron. This effect requires a metabotropic glutamate receptor-mediated rise in Ca
2+ in the astrocyte processes surrounding the neuron and the release of the gliotransmitter ATP, which acts on postsynaptic purinergic receptors. These data provide evidence for a form of distributed synaptic plasticity that is feed-forward, expressed quickly, and mediated by the synaptic activation of neighboring astrocytes.
Expansion of the myocardial extracellular volume (ECV) is a surrogate measure of focal/diffuse fibrosis and is an independent marker of prognosis in chronic heart disease. Changes in ECV may also ...occur after myocardial infarction, acutely because of oedema and in convalescence as part of ventricular remodelling. The objective of this study was to investigate changes in the pattern of distribution of regional (normal, infarcted and oedematous segments) and global left ventricular (LV) ECV using semi-automated methods early and late after reperfused ST-elevation myocardial infarction (STEMI).
Fifty patients underwent cardiovascular magnetic resonance (CMR) imaging acutely (24 h-72 h) and at convalescence (3 months). The CMR protocol included: cines, T2-weighted (T2 W) imaging, pre-/post-contrast T1-maps and LGE-imaging. Using T2 W and LGE imaging on acute scans, 16-segments of the LV were categorised as normal, oedema and infarct. 800 segments (16 per-patient) were analysed for changes in ECV and wall thickening (WT).
From the acute studies, 325 (40.6%) segments were classified as normal, 246 (30.8%) segments as oedema and 229 (28.6%) segments as infarct. Segmental change in ECV between acute and follow-up studies (Δ ECV) was significantly different for normal, oedema and infarct segments (0.8 ± 6.5%, -1.78 ± 9%, -2.9 ± 10.9%, respectively; P < 0.001). Normal segments which demonstrated deterioration in wall thickening at follow-up showed significantly increased Δ ECV compared with normal segments with preserved wall thickening at follow up (1.82 ± 6.05% versus -0.10 ± 6.88%, P < 0.05).
Following reperfused STEMI, normal myocardium demonstrates subtle expansion of the extracellular volume at 3-month follow up. Segmental ECV expansion of normal myocardium is associated with worsening of contractile function.
We study the distribution of projected offsets between the cluster X-ray centroid and the brightest cluster galaxy (BCG) for 65 X-ray-selected clusters from the Local Cluster Substructure Survey, ...with a median redshift of z= 0.23. We find a clear correlation between X-ray/BCG projected offset and the logarithmic slope of the cluster gas density profile at 0.04r500(α), implying that more dynamically disturbed clusters have weaker cool cores. Furthermore, there is a close correspondence between the activity of the BCG, in terms of detected Hα and radio emission, and the X-ray/BCG offset, with the line-emitting galaxies all residing in clusters with X-ray/BCG offsets of ≤15 kpc. Of the BCGs with α < −0.85 and an offset <0.02r500, 96 per cent (23/24) have optical emission and 88 per cent (21/24) are radio active, while none has optical emission outside these criteria. We also study the cluster gas fraction (fgas) within r500 and find a significant correlation with X-ray/BCG projected offset. The mean fgas of the ‘small offset’ clusters (<0.02r500) is 0.106 ± 0.005 (σ= 0.03) compared to 0.145 ± 0.009 (σ= 0.04) for those with an offset >0.02r500, indicating that the total mass may be systematically underestimated in clusters with larger X-ray/BCG offsets. Our results imply a link between cool core strength and cluster dynamical state consistent with the view that cluster mergers can significantly perturb cool cores, and set new constraints on models of the evolution of the intracluster medium.
Collisionless space plasma turbulence can generate reconnecting thin current sheets as suggested by recent results of numerical magnetohydrodynamic simulations. The Magnetospheric Multiscale (MMS) ...mission provides the first serious opportunity to verify whether small ion-electron-scale reconnection, generated by turbulence, resembles the reconnection events frequently observed in the magnetotail or at the magnetopause. Here we investigate field and particle observations obtained by the MMS fleet in the turbulent terrestrial magnetosheath behind quasi-parallel bow shock geometry. We observe multiple small-scale current sheets during the event and present a detailed look of one of the detected structures. The emergence of thin current sheets can lead to electron scale structures. Within these structures, we see signatures of ion demagnetization, electron jets, electron heating, and agyrotropy suggesting that MMS spacecraft observe reconnection at these scales.
Trichuris trichiura is a human parasitic whipworm infecting around 500 million people globally, damaging the physical growth and educational performance of those infected. Current drug treatment ...options are limited and lack efficacy against the worm, preventing an eradication programme. It is therefore important to develop new treatments for trichuriasis. Using Trichuris muris, an established model for T. trichiura, we screened a library of 480 novel drug-like small molecules for compounds causing paralysis of the ex vivo adult parasite. We identified a class of dihydrobenze1,4oxazepin-2(3H)-one compounds with anthelmintic activity against T. muris. Further screening of structurally related compounds and resynthesis of the most potent molecules led to the identification of 20 active dihydrobenzoxazepinones, a class of molecule not previously implicated in nematode control. The most active immobilise adult T. muris with EC50 values around 25-50μM, comparable to the existing anthelmintic levamisole. The best compounds from this chemotype show low cytotoxicity against murine gut epithelial cells, demonstrating selectivity for the parasite. Developing a novel oral pharmaceutical treatment for a neglected disease and deploying it via mass drug administration is challenging. Interestingly, the dihydrobenzoxazepinone OX02983 reduces the ability of embryonated T. muris eggs to establish infection in the mouse host in vivo. Complementing the potential development of dihydrobenzoxazepinones as an oral anthelmintic, this supports an alternative strategy of developing a therapeutic that acts in the environment, perhaps via a spray, to interrupt the parasite lifecycle. Together these results show that the dihydrobenzoxazepinones are a new class of anthelmintic, active against both egg and adult stages of Trichuris parasites. They demonstrate encouraging selectivity for the parasite, and importantly show considerable scope for further optimisation to improve potency and pharmacokinetic properties with the aim of developing a clinical agent.
Magnetized plasma interactions are ubiquitous in astrophysical and laboratory plasmas. Various physical effects have been shown to be important within colliding plasma flows influenced by opposing ...magnetic fields, however, experimental verification of the mechanisms within the interaction region has remained elusive. Here we discuss a laser-plasma experiment whereby experimental results verify that Biermann battery generated magnetic fields are advected by Nernst flows and anisotropic pressure effects dominate these flows in a reconnection region. These fields are mapped using time-resolved proton probing in multiple directions. Various experimental, modelling and analytical techniques demonstrate the importance of anisotropic pressure in semi-collisional, high-β plasmas, causing a reduction in the magnitude of the reconnecting fields when compared to resistive processes. Anisotropic pressure dynamics are crucial in collisionless plasmas, but are often neglected in collisional plasmas. We show pressure anisotropy to be essential in maintaining the interaction layer, redistributing magnetic fields even for semi-collisional, high energy density physics (HEDP) regimes.
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