Astronomical wide-field imaging of interferometric radio data is computationally expensive, especially for the large data volumes created by modern non-coplanar many-element arrays. We present a new ...wide-field interferometric imager that uses the w-stacking algorithm and can make use of the w-snapshot algorithm. The performance dependences of casa's w-projection and our new imager are analysed and analytical functions are derived that describe the required computing cost for both imagers. On data from the Murchison Widefield Array, we find our new method to be an order of magnitude faster than w-projection, as well as being capable of full-sky imaging at full resolution and with correct polarization correction. We predict the computing costs for several other arrays and estimate that our imager is a factor of 2–12 faster, depending on the array configuration. We estimate the computing cost for imaging the low-frequency Square Kilometre Array observations to be 60 PetaFLOPS with current techniques. We find that combining w-stacking with the w-snapshot algorithm does not significantly improve computing requirements over pure w-stacking. The source code of our new imager is publicly released.
We demonstrate efficient transverse compression of a 12.5 MeV/c muon beam stopped in a helium gas target featuring a vertical density gradient and crossed electric and magnetic fields. The muon stop ...distribution extending vertically over 14 mm was reduced to a 0.25 mm size (rms) within 3.5 μs. The simulation including cross sections for low-energy μ+-He elastic and charge exchange (μ+↔ muonium) collisions describes the measurements well. By combining the transverse compression stage with a previously demonstrated longitudinal compression stage, we can improve the phase space density of a μ+ beam by a factor of 1010 with 10−3 efficiency.
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The use of electronic nicotine delivery systems (ENDS), also known as electronic-cigarettes (e-cigs), has raised serious public health concerns, especially in light of the 2019 outbreak of e-cig or ...vaping product use-associated acute lung injury (EVALI). While these cases have mostly been linked to ENDS that contain vitamin E acetate, there is limited research that has focused on the chronic pulmonary effects of the delivery vehicles (i.e., without nicotine and flavoring). Thus, we investigated lung function and immune responses in a mouse model following exposure to the nearly ubiquitous e-cig delivery vehicles, vegetable glycerin (VG) and propylene glycol (PG), used with a specific 70%/30% ratio, with or without vanilla flavoring. We hypothesized that mice exposed sub-acutely to these e-cig aerosols would exhibit lung inflammation and altered lung function. Adult female C57BL/6 mice (
= 11-12 per group) were exposed to filtered air, 70%/30% VG/PG, or 70%/30% VG/PG with a French vanilla flavoring for 2 h a day for 6 weeks. Prior to sacrifice, lung function was assessed. At sacrifice, broncho-alveolar lavage fluid and lung tissue were collected for lipid mediator analysis, flow cytometry, histopathology, and gene expression analyses. Exposures to VG/PG + vanilla e-cig aerosol increased lung tidal and minute volumes and tissue damping. Immunophenotyping of lung immune cells revealed an increased number of dendritic cells, CD4+ T cells, and CD19+ B cells in the VG/PG-exposed group compared to air, irrespective of the presence of vanilla flavoring. Quantification of bioactive lung lipids demonstrated a >3-fold increase of 2-arachidonoylglycerol (2-AG), an anti-inflammatory mediator, and a 2-fold increase of 12-hydroxyeicosatetraenoic acid (12-HETE), another inflammatory mediator, following VG/PG exposure, with or without vanilla flavoring. This suggests that e-cig aerosol vehicles may affect immunoregulatory molecules. We also found that the two e-cig aerosols dysregulated the expression of lung genes. Ingenuity Pathway Analysis revealed that the gene networks that are dysregulated by the VG/PG e-cig aerosol are associated with metabolism of cellular proteins and lipids. Overall, our findings demonstrate that VG and PG, the main constituents of e-liquid formulations, when aerosolized through an e-cig device, are not harmless to the lungs, since they disrupt immune homeostasis.
Using the Murchison Widefield Array (MWA), the low-frequency Square Kilometre Array precursor located in Western Australia, we have completed the GaLactic and Extragalactic All-sky MWA (GLEAM) ...survey, and present the resulting extragalactic catalogue, utilizing the first year of observations. The catalogue covers 24 831 square degrees, over declinations south of +30... and Galactic latitudes outside 10... of the Galactic plane, excluding some areas such as the Magellanic Clouds. It contains 307 455 radio sources with 20 separate flux density measurements across 72-231 MHz, selected from a time- and frequency-integrated image centred at 200 MHz, with a resolution of ...2 arcmin. Over the catalogued region, we estimate that the catalogue is 90 per cent complete at 170 mJy, and 50 per cent complete at 55 mJy, and large areas are complete at even lower flux density levels. Its reliability is 99.97 per cent above the detection threshold of 5..., which itself is typically 50 mJy. These observations constitute the widest fractional bandwidth and largest sky area survey at radio frequencies to date, and calibrate the low-frequency flux density scale of the southern sky to better than 10 per cent. This paper presents details of the flagging, imaging, mosaicking and source extraction/characterization, as well as estimates of the completeness and reliability. All source measurements and images are available online. This is the first in a series of publications describing the GLEAM survey results. (ProQuest: ... denotes formulae/symbols omitted.)
Human land use activities have resulted in large changes to the biogeochemical and biophysical properties of the Earth's surface, with consequences for climate and other ecosystem services. In the ...future, land use activities are likely to expand and/or intensify further to meet growing demands for food, fiber, and energy. As part of the World Climate Research Program Coupled Model Intercomparison Project (CMIP6), the international community has developed the next generation of advanced Earth system models (ESMs) to estimate the combined effects of human activities (e.g., land use and fossil fuel emissions) on the carbon–climate system. A new set of historical data based on the History of the Global Environment database (HYDE), and multiple alternative scenarios of the future (2015–2100) from Integrated Assessment Model (IAM) teams, is required as input for these models. With most ESM simulations for CMIP6 now completed, it is important to document the land use patterns used by those simulations. Here we present results from the Land-Use Harmonization 2 (LUH2) project, which smoothly connects updated historical reconstructions of land use with eight new future projections in the format required for ESMs. The harmonization strategy estimates the fractional land use patterns, underlying land use transitions, key agricultural management information, and resulting secondary lands annually, while minimizing the differences between the end of the historical reconstruction and IAM initial conditions and preserving changes depicted by the IAMs in the future. The new approach builds on a similar effort from CMIP5 and is now provided at higher resolution (0.25°×0.25°) over a longer time domain (850–2100, with extensions to 2300) with more detail (including multiple crop and pasture types and associated management practices) using more input datasets (including Landsat remote sensing data) and updated algorithms (wood harvest and shifting cultivation); it is assessed via a new diagnostic package. The new LUH2 products contain > 50 times the information content of the datasets used in CMIP5 and are designed to enable new and improved estimates of the combined effects of land use on the global carbon–climate system.
Abstract The Green Bank North Celestial Cap survey is one of the largest and most sensitive searches for pulsars and transient radio objects. Observations for the survey have finished; priorities ...have shifted toward long-term monitoring of its discoveries. In this study, we have developed a pipeline to handle large data sets of archival observations and connect them to recent, high-cadence observations taken using the Canadian Hydrogen Intensity Mapping Experiment telescope. This pipeline handles data for 128 pulsars and has produced measurements of spin, positional, and orbital parameters that connect data over observation gaps as large as 2000 days. We have also measured glitches in the timing residuals for five of the pulsars included and proper motion for 19 sources (13 new). We include updates to orbital parameters for 19 pulsars, including nine previously unpublished binaries. For two of these binaries, we provide updated measurements of post-Keplerian binary parameters, which result in much more precise estimates of the total masses of both systems. For PSR J0509+3801, the much improved measurement of the Einstein delay yields much improved mass measurements for the pulsar and its companion, 1.399(6) M ⊙ and 1.412(6) M ⊙ , respectively. For this system, we have also obtained a measurement of the orbital decay due to the emission of gravitational waves, P ̇ B = − 1.37 ( 7 ) × 10 − 12 , which is in agreement with the rate predicted by general relativity for these masses.
Endocannabinoid-metabolizing enzymes are downregulated in response to lipopolysaccharide (LPS)-induced inflammation in mice, which may serve as a negative feedback mechanism to increase ...endocannabinoid levels and reduce inflammation. Increased plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and decreased fatty acid amide hydrolase (FAAH) activity in peripheral lymphocytes from individuals diagnosed with Huntington's disease (HD) suggests that a similar negative feedback system between inflammation and the endocannabinoid system operates in humans. We investigated whether CpG- (unmethylated bacterial DNA) and LPS-induced IL-6 levels in peripheral blood mononuclear cells (PBMCs) from non-HD and HD individuals modulated the activities of endocannabinoid hydrolases monoacylglycerol lipase (MAGL) and carboxylesterase (CES). Baseline plasma IL-6 levels and 2-arachidonoylglycerol (2-AG) hydrolytic activity in PBMC lysates were not different in HD and non-HD individuals. Inhibition of MAGL and CES1 activity in PBMCs using the inhibitors JZL184 and WWL113, respectively, demonstrated that MAGL was the dominant 2-AG hydrolytic enzyme in PBMCs, regardless of disease state. Correlative analyses of 2-AG hydrolytic activity versus enzyme abundance confirmed this conclusion. Flow cytometric analysis of PBMCs showed that MAGL and CES1 were primarily expressed in monocytes and to a lesser extent in lymphocytes. In conclusion, these data suggest that IL-6 did not influence 2-AG hydrolytic activity in human PBMCs; however, monocytic MAGL was shown to be the predominant 2-AG hydrolytic enzyme.
Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, ...are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed that GBM tumor-infiltrating NK cells acquired an altered phenotype associated with impaired lytic function relative to matched peripheral blood NK cells from patients with GBM or healthy donors. We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via av integrin-mediated TGF-β activation. Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-β signaling or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the av integrin/TGF-β axis as a potentially useful therapeutic target in GBM.
This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference ...held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).
Background and aimsThe intestinal microbiota plays a critical role in maintaining human health; however, the mechanisms governing the normal homeostatic number and composition of these microbes are ...largely unknown. Previously it was shown that intestinal alkaline phosphatase (IAP), a small intestinal brush border enzyme, functions as a gut mucosal defence factor limiting the translocation of gut bacteria to mesenteric lymph nodes. In this study the role of IAP in the preservation of the normal homeostasis of the gut microbiota was investigated.MethodsBacterial culture was performed in aerobic and anaerobic conditions to quantify the number of bacteria in the stools of wild-type (WT) and IAP knockout (IAP-KO) C57BL/6 mice. Terminal restriction fragment length polymorphism, phylogenetic analyses and quantitative real-time PCR of subphylum-specific bacterial 16S rRNA genes were used to determine the compositional profiles of microbiotas. Oral supplementation of calf IAP (cIAP) was used to determine its effects on the recovery of commensal gut microbiota after antibiotic treatment and also on the colonisation of pathogenic bacteria.ResultsIAP-KO mice had dramatically fewer and also different types of aerobic and anaerobic microbes in their stools compared with WT mice. Oral supplementation of IAP favoured the growth of commensal bacteria, enhanced restoration of gut microbiota lost due to antibiotic treatment and inhibited the growth of a pathogenic bacterium (Salmonella typhimurium).ConclusionsIAP is involved in the maintenance of normal gut microbial homeostasis and may have therapeutic potential against dysbiosis and pathogenic infections.
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