Very-high-energy gamma-ray emission from high-redshift blazars

We study the possible detection of and properties of very high-energy (VHE) gamma-ray emission (in the energy band above 100 GeV) from high redshift sources. We report on the detection of VHE gamma-ray flux from blazars with redshifts z>0.5. We use the data of Fermi telescope in the energy band above 100 GeV and identify significant sources via cross-correlation of arrival directions of individual VHE gamma-rays with the positions of known Fermi sources. There are thirteen high-redshift sources detected in the VHE band by Fermi/LAT telescope. The present statistics of the Fermi signal from these sources is too low for a sensible study of the effects of suppression of the VHE flux by pair production through interactions with Extragalactic Background Light photons. We find that the detection of these sources with ground-based gamma-ray telescopes would be challenging. However, several sources including BL Lacs PKS 0426-380 at z=1.11, KUV 00311-1938 at z=0.61, B3 1307+433 at z=0.69, PG 1246+586 at z=0.84, Ton 116 at z=1.065 as well as a flat-spectrum radio quasar 4C +55.17 at z=0.89 should be detectable by HESS-II, MAGIC-II and CTA. A high-statistics study of a much larger number of VHE gamma-ray sources at cosmological distances would be possible with the proposed high-altitude Cherenkov telescope [email protected]: 10 pages, 14 figure

Electrical detection of magnetic skyrmions by non-collinear magnetoresistance

Magnetic skyrmions are localised non-collinear spin textures with high potential for future spintronic applications. Skyrmion phases have been discovered in a number of materials and a focus of current research is the preparation, detection, and manipulation of individual skyrmions for an implementation in devices. Local experimental characterization of skyrmions has been performed by, e.g., Lorentz microscopy or atomic-scale tunnel magnetoresistance measurements using spin-polarised scanning tunneling microscopy. Here, we report on a drastic change of the differential tunnel conductance for magnetic skyrmions arising from their non-collinearity: mixing between the spin channels locally alters the electronic structure, making a skyrmion electronically distinct from its ferromagnetic environment. We propose this non-collinear magnetoresistance (NCMR) as a reliable all-electrical detection scheme for skyrmions with an easy implementation into device architectures

Syndromic approach to arboviral diagnostics for global travelers as a basis for infectious disease surveillance

Background Arboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections. Therefore, arbovirus infections are often neglected by travel diagnostics. Here, we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected arboviral diseases in returning travelers. Method To map the patients high at risk of missed clinical arboviral infections we compared the quantity of all arboviral diagnostic requests by physicians in the Netherlands, from 2009 through 2013, with a literature-based assessment of the travelers’ likely exposure to an arbovirus. Results 2153 patients, with travel and clinical history were evaluated. The diagnostic assay for dengue virus (DENV) was the most commonly requested (86%). Of travelers returning from Southeast Asia with symptoms compatible with chikungunya virus (CHIKV), only 55% were tested. For travelers in Europe, arbovirus diagnostics were rarely requested. Over all, diagnostics for most arboviruses were requested only on severe clinical presentation. Conclusion Travel destination and syndrome were used inconsistently for triage of diagnostics, likely resulting in vast under-diagnosis of arboviral infections of public health significance. This study shows the need for more awareness among physicians and standardization of syndromic diagnostic algorithm

Enzymatic Analysis of Recombinant Japanese Encephalitis Virus NS2B(H)-NS3pro Protease with Fluorogenic Model Peptide Substrates

Background Japanese encephalitis virus (JEV), a member of the Flaviviridae family, causes around 68,000 encephalitis cases annually, of which 20–30% are fatal, while 30–50% of the recovered cases develop severe neurological sequelae. Specific antivirals for JEV would be of great importance, particularly in those cases where the infection has become persistent. Being indispensable for flaviviral replication, the NS2B-NS3 protease is a promising target for design of anti-flaviviral inhibitors. Contrary to related flaviviral proteases, the JEV NS2B-NS3 protease is structurally and mechanistically much less characterized. Here we aimed at establishing a straightforward procedure for cloning, expression, purification and biochemical characterization of JEV NS2B(H)-NS3pro protease. Methodology/Principal Findings The full-length sequence of JEV NS2B-NS3 genotype III strain JaOArS 982 was obtained as a synthetic gene. The sequence of NS2B(H)-NS3pro was generated by splicing by overlap extension PCR (SOE-PCR) and cloned into the pTrcHisA vector. Hexahistidine-tagged NS2B(H)-NS3pro, expressed in E. coli as soluble protein, was purified to >95% purity by a single-step immobilized metal affinity chromatography. SDS-PAGE and immunoblotting of the purified enzyme demonstrated NS2B(H)-NS3pro precursor and its autocleavage products, NS3pro and NS2B(H), as 36, 21, and 10 kDa bands, respectively. Kinetic parameters, Km and kcat, for fluorogenic protease model substrates, Boc-GRR-amc, Boc-LRR-amc, Ac-nKRR-amc, Bz-nKRR-amc, Pyr-RTKR-amc and Abz-(R)4SAG-nY-amide, were obtained using inner filter effect correction. The highest catalytic efficiency kcat/Km was found for Pyr-RTKR-amc (kcat/Km: 1962.96±85.0 M−1 s−1) and the lowest for Boc-LRR-amc (kcat/Km: 3.74±0.3 M−1 s−1). JEV NS3pro is inhibited by aprotinin but to a lesser extent than DEN and WNV NS3pro. Conclusions/Significance A simplified procedure for the cloning, overexpression and purification of the NS2B(H)-NS3pro was established which is generally applicable to other flaviviral proteases. Kinetic parameters obtained for a number of model substrates and inhibitors, are useful for the characterization of substrate specificity and eventually for the design of high-throughput assays aimed at antiviral inhibitor discovery

Age-dependent effects of protein restriction on dopamine release

FUNDING AND DISCLOSURE This work was supported by the Biotechnology and Biological Sciences Research Council [grant # BB/M007391/1 to J.E.M.], the European Commission [grant # GA 631404 to J.E.M.], The Leverhulme Trust [grant # RPG-2017-417 to J.E.M.] and the Tromsø Research Foundation [grant # 19-SG-JMcC to J. E. M.). The authors declare no conflict of interest. ACKNOWLEDGEMENTS The authors would like to acknowledge the help and support from the staff of the Division of Biomedical Services, Preclinical Research Facility, University of Leicester, for technical support and the care of experimental animals.Peer reviewedPublisher PD

Racial/Ethnic Disparities in Inadequate Gestational Weight Gain Differ by Pre-pregnancy Weight

OBJECTIVES: Pre-pregnancy body mass index (BMI) varies by race/ethnicity and modifies the association between gestational weight gain (GWG) and adverse pregnancy outcomes, which disproportionately affect racial/ethnic minorities. Yet studies investigating whether racial/ethnic disparities in GWG vary by pre-pregnancy BMI are inconsistent, and none studied nationally representative populations. METHODS: Using categorical measures of GWG adequacy based on Institute of Medicine recommendations, we investigated whether associations between race/ethnicity and GWG adequacy were modified by pre-pregnancy BMI [underweight (<18.5kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), or obese (≥30.0 kg/m(2)) ] among all births to Black, Hispanic, and White mothers in the 1979 USA National Longitudinal Survey of Youth cohort (n=6849 pregnancies; range=1-10). We used generalized estimating equations, adjusted for marital status, parity, smoking during pregnancy, gestational age, and multiple measures of socioeconomic position. RESULTS: Effect measure modification between race/ethnicity and pre-pregnancy BMI was significant for inadequate GWG (Wald test p-value=0.08). Normal weight Black (Risk Ratio (RR)=1.34, 95% confidence interval (CI): 1.18, 1.52) and Hispanic women (RR=1.33, 95%CI: 1.15, 1.54) and underweight Black women (RR=1.38; 95% CI: 1.07, 1.79) experienced an increased risk of inadequate GWG compared to Whites. Differences in risk of inadequate GWG between minority women, compared to White women, were not significant among overweight and obese women. Effect measure modification between race/ethnicity and pre-pregnancy BMI was not significant for excessive GWG. CONCLUSIONS: The magnitude of racial/ethnic disparities in inadequate GWG appears to vary by pre-pregnancy weight class, which should be considered when designing interventions to close racial/ethnic gaps in healthy GWG

An open-access database and analysis tool for perovskite solar cells based on the FAIR data principles

AbstractLarge datasets are now ubiquitous as technology enables higher-throughput experiments, but rarely can a research field truly benefit from the research data generated due to inconsistent formatting, undocumented storage or improper dissemination. Here we extract all the meaningful device data from peer-reviewed papers on metal-halide perovskite solar cells published so far and make them available in a database. We collect data from over 42,400 photovoltaic devices with up to 100 parameters per device. We then develop open-source and accessible procedures to analyse the data, providing examples of insights that can be gleaned from the analysis of a large dataset. The database, graphics and analysis tools are made available to the community and will continue to evolve as an open-source initiative. This approach of extensively capturing the progress of an entire field, including sorting, interactive exploration and graphical representation of the data, will be applicable to many fields in materials science, engineering and biosciences.</jats:p

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS