bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interannual Variability of Atmospheric Gravity Waves in the Martian Thermosphere: Effects of the 2018 Planet‐Encircling Dust Event
Authors: Leelavathi V. , Venkateswara Rao N. , Rao S. V. B. 
Published: November 2020

AbstractWe study the interannual variability of atmospheric gravity waves (GWs) in the Martian thermosphere and their relation to the background temperatures using Ar densities measured by Neutral Gas and Ion Mass Spectrometer/Mars Atmosphere and Volatile Evolution (MAVEN). The amplitudes and wavelengths of the GWs are extracted from the neutral density perturbations in the inbound segment of the MAVEN orbit. The GW amplitudes predominantly lie between 5% and 10% and are mostly less than 30% of the background densities. The horizontal wavelengths are between 50 km and 300 km with peak wavelengths of 100–130 km. GW amplitudes show a significant diurnal variation with larger amplitudes during nighttime and smaller amplitudes during daytime. In addition, the GW amplitudes negatively correlate with the background temperatures indicating the role of convective instability in the saturation of the GWs. Most importantly, the GW amplitudes are larger and the wavelengths are smaller when there was a planet‐encircling dust event in the Mars’ lower atmosphere during 2018. As a result, the typical diurnal variation of GW amplitudes is not apparent. During the lower atmospheric dust event, the GW amplitudes do not show any significant correlation with the background temperatures. It is proposed that the PEDE‐2018 led to changes in the circulation of the mesosphere and lower thermosphere, so that the modified circulation enhanced the upward propagation/reduced the filtering of GWs leading to their enhancement in the upper thermosphere.
Theoretical and practical training improves knowledge of the examination guidelines of the International Standards for Neurological Classification of Spinal Cord Injury
Authors: Franz Steffen , Heutehaus Laura , Weinand Sina , Weidner Norbert , Rupp Rüdiger , Schuld Christian 
Published: November 2020

Abstract
Study design
Prospective pre–post study.

Objectives
International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) represents the most frequently used assessment to determine the level and severity of a spinal cord injury (SCI). The guidelines for ISNCSCI are complex and challenging. Knowledge of its correct execution needs to be imparted precisely. The aim of this study was to investigate whether hands-on instructional courses can increase the knowledge of the ISNCSCI examination guidelines.

Setting
European Multicenter Study about SCI.

Methods
Before and after the instructional courses, participants were asked to complete questionnaires. The set of questions covered the most important aspects of the examination guidelines. Attendees were asked to self-rate their occupation and experience in ISNCSCI.

Results
The comparison of pretest and posttest results of 164 attendees from 2014 to 2018 revealed an improvement of knowledge reflected by an increase of correct answers from 66 ± 17% before to 89 ± 11% after the course (p < 0.01). The improvement was not associated with occupation (p > 0.1). However, the correctness of pretest results differed concerning both the period of experience with ISNCSCI (p < 0.05) and the course language (p < 0.01), while the frequency of execution resulted in differences in the posttest (p = 0.01).

Conclusions
Instructional courses substantially improve knowledge of the ISNCSCI examination guidelines. Differences in knowledge present before the course leveled off after the course. Comprehensive theoretical training is strongly recommended to ensure reliability and validity of ISNCSCI examinations in clinical routine and research. Albeit being practiced in the instructional courses, the benefit of hands-on training still needs to be systematically evaluated in future studies.
Discovery of a novel ferroptosis inducer-talaroconvolutin A—killing colorectal cancer cells in vitro and in vivo
Authors: Xia Yong , Liu Shuzhi , Li Changlin , Ai Zhiying , Shen Wenzhi , Ren Wenqi , Yang Xiaolong 
Published: November 2020

AbstractFerropotsis is among the most important mechanisms of cancer suppression, which could be harnessed for cancer therapy. However, no natural small-molecule compounds with cancer inhibitory activity have been identified to date. In the present study, we reported the discovery of a novel ferroptosis inducer, talaroconvolutin A (TalaA), and the underlying molecular mechanism. We discovered that TalaA killed colorectal cancer cells in dose-dependent and time-dependent manners. Interestingly, TalaA did not induce apoptosis, but strongly triggered ferroptosis. Notably, TalaA was significantly more effective than erastin (a well-known ferroptosis inducer) in suppressing colorectal cancer cells via ferroptosis. We revealed a dual mechanism of TalaA’ action against cancer. On the one hand, TalaA considerably increased reactive oxygen species levels to a certain threshold, the exceeding of which induced ferroptosis. On the other hand, this compound downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. Furthermore, in vivo experiments in mice evidenced that TalaA effectively suppressed the growth of xenografted colorectal cancer cells without obvious liver and kidney toxicities. The findings of this study indicated that TalaA could be a new potential powerful drug candidate for colorectal cancer therapy due to its outstanding ability to kill colorectal cancer cells via ferroptosis induction.
GARP promotes the proliferation and therapeutic resistance of bone sarcoma cancer cells through the activation of TGF-β
Authors: Carrillo-Gálvez Ana Belén , Quintero Juan Esteban , Rodríguez René , Menéndez Sofía T. , Victoria González M. , Blanco-Lorenzo Verónica , Allonca Eva , de Araújo Farias Virgínea , González-Correa Juan Elías , Erill-Sagalés Nadina , Martínez-Zubiaurre Iñigo , Hellevik Turid , Sánchez-Hernández Sabina , Muñoz Pilar , Zurita Federico , Martín Francisco , Rodríguez-Manzaneque Juan Carlos , Anderson Per 
Published: November 2020

AbstractSarcomas are mesenchymal cancers with poor prognosis, representing about 20% of all solid malignancies in children, adolescents, and young adults. Radio- and chemoresistance are common features of sarcomas warranting the search for novel prognostic and predictive markers. GARP/LRRC32 is a TGF-β-activating protein that promotes immune escape and dissemination in various cancers. However, if GARP affects the tumorigenicity and treatment resistance of sarcomas is not known. We show that GARP is expressed by human osteo-, chondro-, and undifferentiated pleomorphic sarcomas and is associated with a significantly worse clinical prognosis. Silencing of GARP in bone sarcoma cell lines blocked their proliferation and induced apoptosis. In contrast, overexpression of GARP promoted their growth in vitro and in vivo and increased their resistance to DNA damage and cell death induced by etoposide, doxorubicin, and irradiation. Our data suggest that GARP could serve as a marker with therapeutic, prognostic, and predictive value in sarcoma. We propose that targeting GARP in bone sarcomas could reduce tumour burden while simultaneously improving the efficacy of chemo- and radiotherapy.
Targeting the CD146/Galectin-9 axis protects the integrity of the blood–brain barrier in experimental cerebral malaria
Authors: Duan Hongxia , Zhao Shuai , Xiang Jianquan , Ju Chenhui , Chen Xuehui , Gramaglia Irene , Yan Xiyun 
Published: November 2020

AbstractCerebral malaria (CM) is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum, in which the destruction of the blood–brain barrier (BBB) is the main cause of death. However, increasing evidence has shown that antimalarial drugs, the current treatment for CM, do little to protect against CM-induced BBB damage. Therefore, a means to alleviate BBB dysfunction would be a promising adjuvant therapy for CM. The adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates neuroinflammation. Here, we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria (eCM). Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells (RBCs) and/or proinflammatory lymphocytes in CNS blood vessels, thereby promoting the disruption of BBB integrity. Mechanistic studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and lymphocytes. Deletion of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM, such as limb paralysis, brain vascular leakage, and death. In addition, AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with eCM. Taken together, our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies.
Ensemble dimensionality reduction and feature gene extraction for single-cell RNA-seq data
Authors: Sun Xiaoxiao , Liu Yiwen , An Lingling 
Published: November 2020

AbstractSingle-cell RNA sequencing (scRNA-seq) technologies allow researchers to uncover the biological states of a single cell at high resolution. For computational efficiency and easy visualization, dimensionality reduction is necessary to capture gene expression patterns in low-dimensional space. Here we propose an ensemble method for simultaneous dimensionality reduction and feature gene extraction (EDGE) of scRNA-seq data. Different from existing dimensionality reduction techniques, the proposed method implements an ensemble learning scheme that utilizes massive weak learners for an accurate similarity search. Based on the similarity matrix constructed by those weak learners, the low-dimensional embedding of the data is estimated and optimized through spectral embedding and stochastic gradient descent. Comprehensive simulation and empirical studies show that EDGE is well suited for searching for meaningful organization of cells, detecting rare cell types, and identifying essential feature genes associated with certain cell types.
Centennial response of Greenland’s three largest outlet glaciers
Authors: Khan Shfaqat A. , Bjørk Anders A. , Bamber Jonathan L. , Morlighem Mathieu , Bevis Michael , Kjær Kurt H. , Mouginot Jérémie , Løkkegaard Anja , Holland David M. , Aschwanden Andy , Zhang Bao , Helm Veit , Korsgaard Niels J. , Colgan William , Larsen Nicolaj K. , Liu Lin , Hansen Karina , Barletta Valentina , Dahl-Jensen Trine S. , Søndergaard Anne Sofie , Csatho Beata M. , Sasgen Ingo , Box Jason , Schenk Toni 
Published: November 2020

AbstractThe Greenland Ice Sheet is the largest land ice contributor to sea level rise. This will continue in the future but at an uncertain rate and observational estimates are limited to the last few decades. Understanding the long-term glacier response to external forcing is key to improving projections. Here we use historical photographs to calculate ice loss from 1880–2012 for Jakobshavn, Helheim, and Kangerlussuaq glacier. We estimate ice loss corresponding to a sea level rise of 8.1 ± 1.1 millimetres from these three glaciers. Projections of mass loss for these glaciers, using the worst-case scenario, Representative Concentration Pathways 8.5, suggest a sea level contribution of 9.1–14.9 mm by 2100. RCP8.5 implies an additional global temperature increase of 3.7 °C by 2100, approximately four times larger than that which has taken place since 1880. We infer that projections forced by RCP8.5 underestimate glacier mass loss which could exceed this worst-case scenario.
Engineered B cells expressing an anti-HIV antibody enable memory retention, isotype switching and clonal expansion
Authors: Nahmad Alessio D. , Raviv Yuval , Horovitz-Fried Miriam , Sofer Ilan , Akriv Tal , Nataf Daniel , Dotan Iris , Carmi Yaron , Burstein David , Wine Yariv , Benhar Itai , Barzel Adi 
Published: November 2020

ABSTRACTHIV viremia can be controlled by chronic antiretroviral therapy. As a potentially single-shot alternative, B cells engineered by CRISPR/Cas9 to express anti-HIV broadly neutralizing antibodies (bNAbs) are capable of secreting high antibody titers. Here, we show that, upon immunization of mice, adoptively transferred engineered B cells home to germinal centers (GC) where they predominate over the endogenous response and differentiate into memory and plasma cells while undergoing class switch recombination (CSR). Immunization with a high affinity antigen increases accumulation in GCs and CSR rates. Boost immunization increases the rate of engineered B cells in GCs and antibody secretion, indicating memory retention. Finally, antibody sequences of engineered B cells in the spleen show patterns of clonal selection. Therefore, B cells can be engineered into what could be a living and evolving drug.
Molecular variation in a functionally divergent homolog of FCA regulates flowering time in Arabidopsis thaliana
Authors: Wang Yunhe , Tao Zhen , Wang Wanyi , Filiault Daniele , Qiu Chunhong , Wang Chuanhong , Wang Hui , Rehman Shamsur , Shi Jian , Zhang Yan , Li Peijin 
Published: November 2020

AbstractThe identification and functional characterization of natural variants in plants are essential for understanding phenotypic adaptation. Here we identify a molecular variation in At2g47310 that contributes to the natural variation in flowering time in Arabidopsis thaliana accessions. This gene, which we term SISTER of FCA (SSF), functions in an antagonistic manner to its close homolog FCA. Genome-wide association analysis screens two major haplotypes of SSF associated with the natural variation in FLC expression, and a single polymorphism, SSF-N414D, is identified as a main contributor. The SSF414N protein variant interacts more strongly with CUL1, a component of the E3 ubiquitination complex, than the SSF414D form, mediating differences in SSF protein degradation and FLC expression. FCA and SSF appear to have arisen through gene duplication after dicot-monocot divergence, with the SSF-N414D polymorphism emerging relatively recently within A. thaliana. This work provides a good example for deciphering the functional importance of natural polymorphisms in different organisms.
Structure of the human sodium leak channel NALCN in complex with FAM155A
Authors: Xie Jiongfang , Ke Meng , Xu Lizhen , Lin Shiyi , Huang Jin , Zhang Jiabei , Yang Fan , Wu Jianping , Yan Zhen 
Published: November 2020

AbstractNALCN, a sodium leak channel expressed mainly in the central nervous system, is responsible for the resting Na+ permeability that controls neuronal excitability. Dysfunctions of the NALCN channelosome, NALCN with several auxiliary subunits, are associated with a variety of human diseases. Here, we report the cryo-EM structure of human NALCN in complex with FAM155A at an overall resolution of 3.1 angstroms. FAM155A forms extensive interactions with the extracellular loops of NALCN that may help stabilize NALCN in the membrane. A Na+ ion-binding site, reminiscent of a Ca2+ binding site in Cav channels, is identified in the unique EEKE selectivity filter. Despite its ‘leaky’ nature, the channel is closed and the intracellular gate is sealed by S6I, II-III linker and III-IV linker. Our study establishes the molecular basis of Na+ permeation and voltage sensitivity, and provides important clues to the mechanistic understanding of NALCN regulation and NALCN channelosome-related diseases.
Chromatin accessibility landscapes of skin cells in systemic sclerosis nominate dendritic cells in disease pathogenesis
Authors: Liu Qian , Zaba Lisa C. , Satpathy Ansuman T. , Longmire Michelle , Zhang Wen , Li Kun , Granja Jeffrey , Guo Chuang , Lin Jun , Li Rui , Tolentino Karen , Kania Gabriela , Distler Oliver , Fiorentino David , Chung Lorinda , Qu Kun , Chang Howard Y. 
Published: November 2020

AbstractSystemic sclerosis (SSc) is a disease at the intersection of autoimmunity and fibrosis. However, the epigenetic regulation and the contributions of diverse cell types to SSc remain unclear. Here we survey, using ATAC-seq, the active DNA regulatory elements of eight types of primary cells in normal skin from healthy controls, as well as clinically affected and unaffected skin from SSc patients. We find that accessible DNA elements in skin-resident dendritic cells (DCs) exhibit the highest enrichment of SSc-associated single-nucleotide polymorphisms (SNPs) and predict the degrees of skin fibrosis in patients. DCs also have the greatest disease-associated changes in chromatin accessibility and the strongest alteration of cell–cell interactions in SSc lesions. Lastly, data from an independent cohort of patients with SSc confirm a significant increase of DCs in lesioned skin. Thus, the DCs epigenome links inherited susceptibility and clinically apparent fibrosis in SSc skin, and can be an important driver of SSc pathogenesis.
The epitaxy of 2D materials growth
Authors: Dong Jichen , Zhang Leining , Dai Xinyue , Ding Feng 
Published: November 2020

AbstractTwo dimensional (2D) materials consist of one to a few atomic layers, where the intra-layer atoms are chemically bonded and the atomic layers are weakly bonded. The high bonding anisotropicity in 2D materials make their growth on a substrate substantially different from the conventional thin film growth. Here, we proposed a general theoretical framework for the epitaxial growth of a 2D material on an arbitrary substrate. Our extensive density functional theory (DFT) calculations show that the propagating edge of a 2D material tends to align along a high symmetry direction of the substrate and, as a conclusion, the interplay between the symmetries of the 2D material and the substrate plays a critical role in the epitaxial growth of the 2D material. Based on our results, we have outlined that orientational uniformity of 2D material islands on a substrate can be realized only if the symmetry group of the substrate is a subgroup of that of the 2D material. Our predictions are in perfect agreement with most experimental observations on 2D materials’ growth on various substrates known up to now. We believe that this general guideline will lead to the large-scale synthesis of wafer-scale single crystals of various 2D materials in the near future.
Uncertainty quantification and reduction in metal additive manufacturing
Authors: Wang Zhuo , Jiang Chen , Liu Pengwei , Yang Wenhua , Zhao Ying , Horstemeyer Mark F. , Chen Long-Qing , Hu Zhen , Chen Lei 
Published: November 2020

AbstractUncertainty quantification (UQ) in metal additive manufacturing (AM) has attracted tremendous interest in order to dramatically improve product reliability. Model-based UQ, which relies on the validity of a computational model, has been widely explored as a potential substitute for the time-consuming and expensive UQ solely based on experiments. However, its adoption in the practical AM process requires overcoming two main challenges: (1) the inaccurate knowledge of uncertainty sources and (2) the intrinsic uncertainty associated with the computational model. Here, we propose a data-driven framework to tackle these two challenges by combining high throughput physical/surrogate model simulations and the AM-Bench experimental data from the National Institute of Standards and Technology (NIST). We first construct a surrogate model, based on high throughput physical simulations, for predicting the three-dimensional (3D) melt pool geometry and its uncertainty with respect to AM parameters and uncertainty sources. We then employ a sequential Bayesian calibration method to perform experimental parameter calibration and model correction to significantly improve the validity of the 3D melt pool surrogate model. The application of the calibrated melt pool model to UQ of the porosity level, an important quality factor, of AM parts, demonstrates its potential use in AM quality control. The proposed UQ framework can be generally applicable to different AM processes, representing a significant advance toward physics-based quality control of AM products.
The role of chromium content in the long-term atmospheric corrosion process
Authors: Sun Baozhuang , Zuo Xiaomei , Cheng Xuequn , Li Xiaogang 
Published: November 2020

AbstractThe corrosion of alloy steels with different amounts of Cr was studied using electrochemical tests, wet–dry cycle corrosion, X-ray diffraction, and Kelvin probe force microscopy. The results show that the content of Cr is positively correlated with the corrosion resistance of bare steel, but the corrosion resistance of atmospheric corrosion does not show the same pattern. The atmospheric corrosion resistance of Cr-containing steel exhibits three different stages with the change of Cr element content. When the Cr content is in the range of 1–4%, the corrosion rate is high and does not change within the Cr content. As the Cr content was further increased from 4 to 7%, the corrosion rate exhibited a linear decrease and then drops rapidly when the Cr content reaches 8%. These three different corrosion rate stages are related to the influence of Cr content on Fe3O4 content in the rust layer.
Seasonal weather and climate prediction over area burned in grasslands of northeast China
Authors: Shabbir Ali Hassan , Zhang Jiquan , Groninger John W. , van Etten Eddie J. B. , Sarkodie Samuel Asumadu , Lutz James A. , Valencia Carlos F. 
Published: November 2020

AbstractGrassland fire dynamics are subject to myriad climatic, biological, and anthropogenic drivers, thresholds, and feedbacks and therefore do not conform to assumptions of statistical stationarity. The presence of non-stationarity in time series data leads to ambiguous results that can misinform regional-level fire management strategies. This study employs non-stationarity in time series data among multiple variables and multiple intensities using dynamic simulations of autoregressive distributed lag models to elucidate key drivers of climate and ecological change on burned grasslands in Xilingol, China. We used unit root methods to select appropriate estimation methods for further analysis. Using the model estimations, we developed scenarios emulating the effects of instantaneous changes (i.e., shocks) of some significant variables on climate and ecological change. Changes in mean monthly wind speed and maximum temperature produce complex responses on area burned, directly, and through feedback relationships. Our framework addresses interactions among multiple drivers to explain fire and ecosystem responses in grasslands, and how these may be understood and prioritized in different empirical contexts needed to formulate effective fire management policies.
Accelerated MRI-predicted brain ageing and its associations with cardiometabolic and brain disorders
Authors: Kolbeinsson Arinbjörn , Filippi Sarah , Panagakis Yannis , Matthews Paul M. , Elliott Paul , Dehghan Abbas , Tzoulaki Ioanna 
Published: November 2020

AbstractBrain structure in later life reflects both influences of intrinsic aging and those of lifestyle, environment and disease. We developed a deep neural network model trained on brain MRI scans of healthy people to predict “healthy” brain age. Brain regions most informative for the prediction included the cerebellum, hippocampus, amygdala and insular cortex. We then applied this model to data from an independent group of people not stratified for health. A phenome-wide association analysis of over 1,410 traits in the UK Biobank with differences between the predicted and chronological ages for the second group identified significant associations with over 40 traits including diseases (e.g., type I and type II diabetes), disease risk factors (e.g., increased diastolic blood pressure and body mass index), and poorer cognitive function. These observations highlight relationships between brain and systemic health and have implications for understanding contributions of the latter to late life dementia risk.