bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of truncated Kir6.2 promotes insertion of functionally inverted ATP-sensitive K+ channels
Authors: Heitz Benjamin A. , Bränström Robert , Yang Wei , Huang Yiding , Moede Tilo , Leibiger Ingo B. , Leibiger Barbara , Chen Liu Qi , Yu Jia , Yang Shao-Nian , Larsson Olof , Saavedra S. Scott , Berggren Per-Olof , Aspinwall Craig A. 
Published: November 2021

AbstractATP-sensitive K+ (KATP) channels couple cellular metabolism to electrical activity in many cell types. Wild-type KATP channels are comprised of four pore forming (Kir6.x) and four regulatory (sulfonylurea receptor, SURx) subunits that each contain RKR endoplasmic reticulum retention sequences that serve to properly translocate the channel to the plasma membrane. Truncated Kir6.x variants lacking RKR sequences facilitate plasma membrane expression of functional Kir6.x in the absence of SURx; however, the effects of channel truncation on plasma membrane orientation have not been explored. To investigate the role of truncation on plasma membrane orientation of ATP sensitive K+ channels, three truncated variants of Kir6.2 were used (Kir6.2ΔC26, 6xHis-Kir6.2ΔC26, and 6xHis-EGFP-Kir6.2ΔC26). Oocyte expression of Kir6.2ΔC26 shows the presence of a population of inverted inserted channels in the plasma membrane, which is not present when co-expressed with SUR1. Immunocytochemical staining of intact and permeabilized HEK293 cells revealed that the N-terminus of 6xHis-Kir6.2ΔC26 was accessible on both sides of the plasma membrane at roughly equivalent ratios, whereas the N-terminus of 6xHis-EGFP-Kir6.2Δ26 was only accessible on the intracellular face. In HEK293 cells, whole-cell electrophysiological recordings showed a ca. 50% reduction in K+ current upon addition of ATP to the extracellular solution for 6xHis-Kir6.2ΔC26, though sensitivity to extracellular ATP was not observed in 6xHis-EGFP-Kir6.2ΔC26. Importantly, the population of channels that is inverted exhibited similar function to properly inserted channels within the plasma membrane. Taken together, these data suggest that in the absence of SURx, inverted channels can be formed from truncated Kir6.x subunits that are functionally active which may provide a new model for testing pharmacological modulators of Kir6.x, but also indicates the need for added caution when using truncated Kir6.2 mutants.
Biomarkers of subclinical atherosclerosis in patients with psoriasis
Authors: Kaiser Hannah , Wang Xing , Kvist-Hansen Amanda , Krakauer Martin , Gørtz Peter Michael , McCauley Benjamin D. , Skov Lone , Becker Christine , Hansen Peter Riis 
Published: November 2021

AbstractPsoriasis is linked with increased risk of cardiovascular disease (CVD) that is underestimated by traditional risk stratification. We conducted a large-scale plasma proteomic analysis by use of a proximity extension assay in 85 patients with a history of moderate-to-severe psoriasis with or without established atherosclerotic CVD. Differentially expressed proteins associated with CVD were correlated with subclinical atherosclerotic markers including vascular inflammation determined by18F-fluorodeoxyglucose positron emission tomography/computed tomography, carotid intima-media thickness (CIMT), carotid artery plaques, and coronary artery calcium score (CCS) in the patients without CVD and statin treatment. We also examined the association between the neutrophil-to-lymphocyte ratio (NLR) and subclinical atherosclerosis. In unadjusted analyses, growth differentiation factor-15 (GDF-15) levels and NLR were increased, while tumor necrosis factor (TNF)-related activation-inducing ligand (TRANCE) and TNF-related apoptosis-induced ligand (TRAIL) levels were decreased in patients with established CVD compared to those without CVD. Among patients with psoriasis without CVD and statin treatment, GDF-15 levels were negatively associated with vascular inflammation in the ascending aorta and entire aorta, and positively associated with CIMT and CCS. NLR was positively associated with vascular inflammation in the carotid arteries. Our data suggest that circulating GDF-15 levels and NLR might serve as biomarkers of subclinical atherosclerosis in patients with psoriasis.
Peptide barcoding for one-pot evaluation of sequence–function relationships of nanobodies
Authors: Matsuzaki Yusei , Aoki Wataru , Miyazaki Takumi , Aburaya Shunsuke , Ohtani Yuta , Kajiwara Kaho , Koike Naoki , Minakuchi Hiroyoshi , Miura Natsuko , Kadonosono Tetsuya , Ueda Mitsuyoshi 
Published: November 2021

AbstractOptimisation of protein binders relies on laborious screening processes. Investigation of sequence–function relationships of protein binders is particularly slow, since mutants are purified and evaluated individually. Here we developed peptide barcoding, a high-throughput approach for accurate investigation of sequence–function relationships of hundreds of protein binders at once. Our approach is based on combining the generation of a mutagenised nanobody library fused with unique peptide barcodes, the formation of nanobody–antigen complexes at different ratios, their fine fractionation by size-exclusion chromatography and quantification of peptide barcodes by targeted proteomics. Applying peptide barcoding to an anti-GFP nanobody as a model, we successfully identified residues important for the binding affinity of anti-GFP nanobody at once. Peptide barcoding discriminated subtle changes in KD at the order of nM to sub-nM. Therefore, peptide barcoding is a powerful tool for engineering protein binders, enabling reliable one-pot evaluation of sequence–function relationships.
Genomic diversity of SARS-CoV-2 in Oxford during United Kingdom’s first national lockdown
Authors: Munis Altar M. , Andersson Monique , Mobbs Alexander , Hyde Stephen C. , Gill Deborah R. 
Published: November 2021

AbstractEpidemiological efforts to model the spread of SARS-CoV-2, the virus that causes COVID-19, are crucial to understanding and containing current and future outbreaks and to inform public health responses. Mutations that occur in viral genomes can alter virulence during outbreaks by increasing infection rates and helping the virus evade the host immune system. To understand the changes in viral genomic diversity and molecular epidemiology in Oxford during the first wave of infections in the United Kingdom, we analyzed 563 clinical SARS-CoV-2 samples via whole-genome sequencing using Nanopore MinION sequencing. Large-scale surveillance efforts during viral epidemics are likely to be confounded by the number of independent introductions of the viral strains into a region. To avoid such issues and better understand the selection-based changes occurring in the SARS-CoV-2 genome, we utilized local isolates collected during the UK’s first national lockdown whereby personal interactions, international and national travel were considerably restricted and controlled. We were able to track the short-term evolution of the virus, detect the emergence of several mutations of concern or interest, and capture the viral diversity of the region. Overall, these results demonstrate genomic pathogen surveillance efforts have considerable utility in controlling the local spread of the virus.
Genomic surveillance of enterovirus associated with aseptic meningitis cases in southern Spain, 2015–2018
Authors: Gámbaro Fabiana , Pérez Ana Belén , Agüera Eduardo , Prot Matthieu , Martínez-Martínez Luis , Cabrerizo María , Simon-Loriere Etienne , Fernandez-Garcia Maria Dolores 
Published: November 2021

AbstractNew circulating Enterovirus (EV) strains often emerge through recombination. Upsurges of recombinant non-polio enteroviruses (NPEVs) associated with neurologic manifestations such as EVA71 or Echovirus 30 (E30) are a growing public health concern in Europe. Only a few complete genomes of EVs circulating in Spain are available in public databases, making it difficult to address the emergence of recombinant EVs, understand their evolutionary relatedness and the possible implication in human disease. We have used metagenomic (untargeted) NGS to generate full-length EV genomes from CSF samples of EV-positive aseptic meningitis cases in Southern Spain between 2015 and 2018. Our analyses reveal the co-circulation of multiple Enterovirus B (EV-B) types (E6, E11, E13 and E30), including a novel E13 recombinant form. We observed a genetic turnover where emergent lineages (C1 for E6 and I [tentatively proposed in this study] for E30) replaced previous lineages circulating in Spain, some concomitant with outbreaks in other parts of Europe. Metagenomic sequencing provides an effective approach for the analysis of EV genomes directly from PCR-positive CSF samples. The detection of a novel, disease-associated, recombinant form emphasizes the importance of genomic surveillance to monitor spread and evolution of EVs.
Recent advances in PTP1B signaling in metabolism and cancer
Authors: Villamar-Cruz Olga , Loza-Mejía Marco A. , Arias-Romero Luis E. , Camacho-Arroyo Ignacio 
Published: November 2021

Abstract
Protein tyrosine phosphorylation is one of the major post-translational modifications in eukaryotic cells and represents a critical regulatory mechanism of a wide variety of signaling pathways. Aberrant protein tyrosine phosphorylation has been linked to various diseases, including metabolic disorders and cancer. Few years ago, protein tyrosine phosphatases (PTPs) were considered as tumor suppressors, able to block the signals emanating from receptor tyrosine kinases. However, recent evidence demonstrates that misregulation of PTPs activity plays a critical role in cancer development and progression. Here, we will focus on PTP1B, an enzyme that has been linked to the development of type 2 diabetes and obesity through the regulation of insulin and leptin signaling, and with a promoting role in the development of different types of cancer through the activation of several pro-survival signaling pathways. In this review, we discuss the molecular aspects that support the crucial role of PTP1B in different cellular processes underlying diabetes, obesity and cancer progression, and its visualization as a promising therapeutic target.
Hierarchical optimization: A hybrid processing for downlink massive MU‐MIMO mmWave systems
Authors: Ortega Alvaro Javier 
Published: November 2021

AbstractCommunications using the millimeter wave (mmWave) spectrum are a mainstream technology of the next generation systems due to their huge available bandwidth. However, the mmWave band will experience much more propagation loss than a low‐frequency band. Conventional precoding techniques are impractical in mmWave scenarios due to manufacturing costs and power consumption. Hybrid alternatives have been considered as a promising technology to provide a compromise between hardware complexity and system performance by reducing the number of radio‐frequency (RF) chains. In this paper, a hybrid processing design for downlink in mmWave scenarios is proposed, where the number of RF chains is reduced to the number of data streams. The precodification process is made by a three‐stage‐based hybrid precoder, whereas in the terminals, the equalization process only requires a low complex analog combiner. The three stages of the hybrid precoder are designed by a hierarchical strategy. The first stage addresses the phase shifters aiming to maximize the sum‐rate system, whereas the second and third stages are dedicated to mitigating the inter‐user interference effects. The proposed methodology gets a robust signal processing that can greatly mitigate the side effects of hardware reduction. Numerical results in terms of bit error rate (BER) and sum‐rate evidence that the proposed method not only overcomes other hybrid precoders/combiners but also reaches the same performance as a fully digital technique in some scenarios.
Feature fusion for inverse synthetic aperture radar image classification via learning shared hidden space
Authors: Lin Wenhao , Gao Xunzhang 
Published: November 2021

AbstractMulti‐sensor fusion recognition is a meaningful task in ISAR image recognition. Compared with a single sensor, multi‐sensor fusion can provide richer target information, which is conducive to more accurate and robust identification. However, previous deep learning‐based fusion methods do not effectively deal with the redundancy and complementarity of information between different sources. In this letter, we construct a shared hidden space to align features from different sources. Accordingly, we design an end‐to‐end deep fusion framework to fuse dual ISAR images at the feature level. For combining the multi‐source information, deep generalised canonical correlation analysis (DGCCA) is used as the loss item to map features extracted from dual input onto the shared hidden space. Moreover, we propose an efficient and lightweight spatial attention module, named united attention module, which can be embedded between dual‐stream convolutional neural networks (CNNs) to promote DGCCA optimisation by information interaction. Compared with other deep fusion frameworks, our model obtains the competitive performance in ISAR image fusion for classification.
Probabilistic classification of X-ray sources applied to Swift-XRT and XMM-Newton catalogs
Authors: Tranin Hugo , Godet Olivier , Webb Natalie , Primorac Daria 
Published: November 2021

Context. Serendipitous X-ray surveys have proven to be an efficient way to find rare objects, for example tidal disruption events, changing-look active galactic nuclei (AGN), binary quasars, ultraluminous X-ray sources, and intermediate mass black holes. With the advent of very large X-ray surveys, an automated classification of X-ray sources becomes increasingly valuable.
Aims. This work proposes a revisited naive Bayes classification of the X-ray sources in the Swift-XRT and XMM-Newton catalogs into four classes – AGN, stars, X-ray binaries (XRBs), and cataclysmic variables (CVs) – based on their spatial, spectral, and timing properties and their multiwavelength counterparts. An outlier measure is used to identify objects of other natures. The classifier is optimized to maximize the classification performance of a chosen class (here XRBs), and it is adapted to data mining purposes.
Methods. We augmented the X-ray catalogs with multiwavelength data, source class, and variability properties. We then built a reference sample of about 25 000 X-ray sources of known nature. From this sample, the distribution of each property was carefully estimated and taken as reference to assign probabilities of belonging to each class. The classification was then performed on the whole catalog, combining the information from each property.
Results. Using the algorithm on the Swift reference sample, we retrieved 99%, 98%, 92%, and 34% of AGN, stars, XRBs, and CVs, respectively, and the false positive rates are 3%, 1%, 9%, and 15%. Similar results are obtained on XMM sources. When applied to a carefully selected test sample, representing 55% of the X-ray catalog, the classification gives consistent results in terms of distributions of source properties. A substantial fraction of sources not belonging to any class is efficiently retrieved using the outlier measure, as well as AGN and stars with properties deviating from the bulk of their class. Our algorithm is then compared to a random forest method; the two showed similar performances, but the algorithm presented in this paper improved insight into the grounds of each classification.
Conclusions. This robust classification method can be tailored to include additional or different source classes and can be applied to other X-ray catalogs. The transparency of the classification compared to other methods makes it a useful tool in the search for homogeneous populations or rare source types, including multi-messenger events. Such a tool will be increasingly valuable with the development of surveys of unprecedented size, such as LSST, SKA, and Athena, and the search for counterparts of multi-messenger events.
Implementation of disequilibrium chemistry to spectral retrieval code ARCiS and application to 16 exoplanet transmission spectra
Authors: Kawashima Yui , Min Michiel 
Published: November 2021

Context. The retrieval approach is currently a standard method for deriving atmospheric properties from observed spectra of exoplanets. However, the approach ignores disequilibrium chemistry in most current retrieval codes, which can lead to a misinterpretation of the metallicity or elemental abundance ratios of the atmosphere.
Aims. We have implemented the disequilibrium effect of vertical mixing or quenching for the major species in hydrogen and helium-dominated atmospheres, namely CH4, CO, H2O, NH3, N2, and CO2, for the spectral retrieval code ARCiS with a physical basis.
Methods. We used the chemical relaxation method and developed a module to compute the profiles of molecular abundances, taking the disequilibrium effect into account. Then, using ARCiS updated with this module, we performed retrievals of the observed transmission spectra of 16 exoplanets with sizes ranging from that of Jupiter to mini-Neptunes.
Results. We find indications of disequilibrium chemistry for HD 209458b (≥4.1σ) and WASP-39b (≥2.7σ). The retrieved spectrum of HD 209458b exhibits a strong NH3 absorption feature at 10.5 μm that is accessible by JWST owing to an enhanced abundance of NH3 due to the quenching effect. This feature is absent in the spectrum retrieved assuming equilibrium chemistry, which makes HD 209458b an ideal target for studying disequilibrium chemistry in exoplanet atmospheres. Moreover, for HAT-P-11b and GJ 436b, we obtain relatively different results compared to the retrieval with the equilibrium assumption, such as a 2.9σ difference for the C/O ratio. We have also examined the retrieved eddy diffusion coefficient but could not identify a trend over the equilibrium temperature, possibly due to the limits of the current observational precision.
Conclusions. We have demonstrated that the assumption of equilibrium chemistry can lead to a misinterpretation of the observed data, showing that spectral retrieval with a consideration of disequilibrium chemistry is essential in the era of JWST and Ariel.
Fundamental stellar parameters of benchmark stars from CHARA interferometry
Authors: Karovicova I. , White T. R. , Nordlander T. , Casagrande L. , Ireland M. , Huber D. 
Published: November 2021

Context. Stellar models applied to large stellar surveys of the Milky Way need to be properly tested against a sample of stars with highly reliable fundamental stellar parameters. We have established a programme aiming to deliver such a sample of stars.
Aims. Here we present new fundamental stellar parameters of nine dwarf stars that will be used as benchmark stars for large stellar surveys. One of these stars is the solar-twin 18 Sco, which is also one of the Gaia-ESO benchmarks. The goal is to reach a precision of 1% in effective temperature (Teff). This precision is important for accurate determinations of the full set of fundamental parameters and abundances of stars observed by the surveys.
Methods. We observed HD 131156 (ξ Boo), HD 146233 (18 Sco), HD 152391, HD 173701, HD 185395 (θ Cyg), HD 186408 (16 Cyg A), HD 186427 (16 Cyg B), HD 190360, and HD 207978 (15 Peg) using the high angular resolution optical interferometric instrument PAVO at the CHARA Array. We derived limb-darkening corrections from 3D model atmospheres and determined Teff directly from the Stefan–Boltzmann relation, with an iterative procedure to interpolate over tables of bolometric corrections. Surface gravities were estimated from comparisons to Dartmouth stellar evolution model tracks. We collected spectroscopic observations from the ELODIE spectrograph and estimated metallicities ([Fe/H]) from a 1D non-local thermodynamic equilibrium (NLTE) abundance analysis of unblended lines of neutral and singly ionised iron.
Results. For eight of the nine stars we measure the Teff ⪅ 1%, and for one star better than 2%. We determined the median uncertainties in log g and [Fe/H] as 0.015 dex and 0.05 dex, respectively.
Conclusions. This study presents updated fundamental stellar parameters of nine dwarf stars that can be used as a new set of benchmarks. All the fundamental stellar parameters were based on consistently combining interferometric observations, 3D limb-darkening modelling, and spectroscopic analysis. The next paper in this series will extend our sample to giants in the metal-rich range.
A low-jitter timing generator based on completely on-chip self-measurement and calibration in a field programmable gate array
Authors: Qiu Wenjie , Xie Jianfeng , Liu Qinying , Han Xiaotao 
Published: November 2021

This paper presents a high-stability and low-jitter Arbitrary Timing Generator (ATG) design based on the Xilinx Field Programmable Gate Array (FPGA) and its special integrated delay line. In recent years, FPGA-based or application specific integrated circuit-based delay lines have been used to achieve picosecond-level timing resolution. Devices with pure digital delay methods can only acquire triggers at the clock rising edges when triggered externally. Therefore, there is a large time irregularity caused by the uncertainty of the entry time of the trigger, which is difficult to compensate and leads to a large time jitter of outputs. We describe the design of an ATG that includes jitter self-measurement and calibration methods, which is available for both internal and external trigger modes. This structure is completely based on the FPGA’s own resources and has the advantages of being simple and flexible. Experimental results show a sub-nanosecond timing resolution of 78 ± 20 ps with a minimum of 120 ps and a time jitter of 160 ± 20 ps in the external trigger mode after compensation.
No evidence for systematic voter fraud: A guide to statistical claims about the 2020 election
Authors: Eggers Andrew C. , Garro Haritz , Grimmer Justin 
Published: November 2021

Significance
President Donald Trump claimed that the 2020 US presidential election was stolen; millions of Americans apparently believed him. We assess the most prominent statistical claims offered by Trump and his allies as evidence of election fraud, including claims about Dominion voting machines switching votes from Trump to Biden, suspiciously high turnout in Democratic strongholds, and the supposedly inexplicable failure of Biden to win “bellwether counties.” We use a combination of statistical reasoning and original data analysis to assess these claims. We hope our analysis contributes to public discussion about the integrity of the 2020 election and broader challenges of election security and election administration.
Flexible cyclic-olefin with enhanced dipolar relaxation for harsh condition electrification
Authors: Wu Chao , Deshmukh Ajinkya A. , Yassin Omer , Zhou Jierui , Alamri Abdullah , Vellek John , Shukla Stuti , Sotzing Michael , Casalini Riccardo , Sotzing Gregory A. , Cao Yang 
Published: November 2021

SignificanceFlexible polymer dielectrics operable under not only electrical but also thermal extremes are desired for high-power-density and high-payload-efficiency electrification. Unfortunately, state-of-the-art high-temperature polymers exhibit largely reduced electrical energy storage performance, as traditionally their bandgaps are inversely correlated to the dielectric constants. Here, an all-organic polymer was reported with high dielectric constant originating from the enhanced dipolar relaxation, an uncompromised large bandgap of 4.84 eV, and a high glass transition temperature of 178 °C by locally decoupling the conjugation of polymer backbones. This rational strategic design uncovers a large unexplored space for the design of polymer dielectrics for multiple harsh conditions.