bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding Top‐of‐Atmosphere Flux Bias in the AeroCom Phase III Models: A Clear‐Sky Perspective
Authors: Su Wenying , Liang Lusheng , Myhre Gunnar , Thorsen Tyler J. , Loeb Norman G. , Schuster Gregory L. , Ginoux Paul , Paulot Fabien , Neubauer David , Checa‐Garcia Ramiro , Matsui Hitoshi , Tsigaridis Kostas , Skeie Ragnhild B. , Takemura Toshihiko , Bauer Susanne E. , Schulz Michael 
Published: August 2021

AbstractBiases in aerosol optical depths (AOD) and land surface albedos in the AeroCom models are manifested in the top‐of‐atmosphere (TOA) clear‐sky reflected shortwave (SW) fluxes. Biases in the SW fluxes from AeroCom models are quantitatively related to biases in AOD and land surface albedo by using their radiative kernels. Over ocean, AOD contributes about 25% to the S–N mean SW flux bias for the multi‐model mean (MMM) result. Over land, AOD and land surface albedo contribute about 40% and 30%, respectively, to the S–N mean SW flux bias for the MMM result. Furthermore, the spatial patterns of the SW flux biases derived from the radiative kernels are very similar to those between models and CERES observation, with the correlation coefficient of 0.6 over ocean and 0.76 over land for MMM using data of 2010. Satellite data used in this evaluation are derived independently from each other, consistencies in their bias patterns when compared with model simulations suggest that these patterns are robust. This highlights the importance of evaluating related variables in a synergistic manner to provide an unambiguous assessment of the models, as results from single parameter assessments are often confounded by measurement uncertainty. Model biases in land surface albedos can and must be corrected to accurately calculate TOA flux. We also compare the AOD trend from three models with the observation‐based counterpart. These models reproduce all notable trends in AOD except the decreasing trend over eastern China and the adjacent oceanic regions due to limitations in the emission data set.
Reelin depletion alleviates multiple myeloma bone disease by promoting osteogenesis and inhibiting osteolysis
Authors: Dou Aixia , Zhang Ying , Wang Yongjing , Liu Xiaoli , Guo Yanan 
Published: August 2021

AbstractExtracellular matrix glycoprotein Reelin is associated with tumor metastasis and prognosis in various malignancies. However, its effects on multiple myeloma (MM) are not fully understood. Here, we investigated the regulatory effects of Reelin on MM and its underlying pathogenic mechanisms. Lentivirus plasmid containing short hairpin RNA targeting Reelin (LV3-Reln) was transfected into SP2/0 cells to knockdown Reelin expression. Flow cytometry assay analyzed cell cycle and apoptosis while Transwell assay evaluated invasiveness. BALB/c mice were inoculated with LV3-Reln-transfected SP2/0 cells to establish MM model. Primary myeloma cells and osteoblasts/osteoclast were isolated from tumor tissue and limb long bones respectively. ELISA examined serum biomarkers and immunohistochemistry detected immunoglobulin light chain expression. Morphological changes and osteoclast/osteoblast differentiation were observed by histological staining. mRNA and proteins expression were determined by qPCR and WB. In vitro studies showed that Reelin depletion regulated osteolysis and osteogenesis balance, cell cycle, invasiveness, and apoptosis in SP2/0 cells. In LV3-Reln mice, tumor growth and invasiveness were suppressed, meanwhile, reduced osteoclast activation and enhanced osteoblast activity were observed. Reelin knockdown alleviated extramedullary morbidity and inhibited spleen immune cell apoptosis by down-regulating CDK5, IL-10, and Cyto-C expression. Furthermore, reduced Reelin expression restrained osteoclast differentiation while promoted osteogenesis in the bone of LV3-Reln mice. This was further supported by down-regulation of osteolytic specific mRNAs and proteins (Trap, Mmp9, Ctsk, Clcn7) and up-regulation of osteogenic specific ones (COL-1, Runx2, β-Catenin). Reelin exerted important impacts on myeloma development through rebalancing osteolysis and osteogenesis, thus might be a potential therapeutic target for MM.
Global spread of Salmonella Enteritidis via centralized sourcing and international trade of poultry breeding stocks
Authors: Li Shaoting , He Yingshu , Mann David Ames , Deng Xiangyu 
Published: August 2021

AbstractA pandemic of Salmonella enterica serotype Enteritidis emerged in the 1980s due to contaminated poultry products. How Salmonella Enteritidis rapidly swept through continents remains a historical puzzle as the pathogen continues to cause outbreaks and poultry supply becomes globalized. We hypothesize that international trade of infected breeding stocks causes global spread of the pathogen. By integrating over 30,000 Salmonella Enteritidis genomes from 98 countries during 1949–2020 and international trade of live poultry from the 1980s to the late 2010s, we present multifaceted evidence that converges on a high likelihood, global scale, and extended protraction of Salmonella Enteritidis dissemination via centralized sourcing and international trade of breeding stocks. We discovered recent, genetically near-identical isolates from domestically raised poultry in North and South America. We obtained phylodynamic characteristics of global Salmonella Enteritidis populations that lend spatiotemporal support for its dispersal from centralized origins during the pandemic. We identified concordant patterns of international trade of breeding stocks and quantitatively established a driving role of the trade in the geographic dispersal of Salmonella Enteritidis, suggesting that the centralized origins were infected breeding stocks. Here we demonstrate the value of integrative and hypothesis-driven data mining in unravelling otherwise difficult-to-probe pathogen dissemination from hidden origins.
Predicting base editing outcomes with an attention-based deep learning algorithm trained on high-throughput target library screens
Authors: Marquart Kim F. , Allam Ahmed , Janjuha Sharan , Sintsova Anna , Villiger Lukas , Frey Nina , Krauthammer Michael , Schwank Gerald 
Published: August 2021

AbstractBase editors are chimeric ribonucleoprotein complexes consisting of a DNA-targeting CRISPR-Cas module and a single-stranded DNA deaminase. They enable transition of C•G into T•A base pairs and vice versa on genomic DNA. While base editors have great potential as genome editing tools for basic research and gene therapy, their application has been hampered by a broad variation in editing efficiencies on different genomic loci. Here we perform an extensive analysis of adenine- and cytosine base editors on a library of 28,294 lentivirally integrated genetic sequences and establish BE-DICT, an attention-based deep learning algorithm capable of predicting base editing outcomes with high accuracy. BE-DICT is a versatile tool that in principle can be trained on any novel base editor variant, facilitating the application of base editing for research and therapy.
T cell receptor recognition of hybrid insulin peptides bound to HLA-DQ8
Authors: Tran Mai T. , Faridi Pouya , Lim Jia Jia , Ting Yi Tian , Onwukwe Goodluck , Bhattacharjee Pushpak , Jones Claerwen M. , Tresoldi Eleonora , Cameron Fergus J. , La Gruta Nicole L. , Purcell Anthony W. , Mannering Stuart I. , Rossjohn Jamie , Reid Hugh H. 
Published: August 2021

AbstractHLA-DQ8, a genetic risk factor in type I diabetes (T1D), presents hybrid insulin peptides (HIPs) to autoreactive CD4+ T cells. The abundance of spliced peptides binding to HLA-DQ8 and how they are subsequently recognised by the autoreactive T cell repertoire is unknown. Here we report, the HIP (GQVELGGGNAVEVLK), derived from splicing of insulin and islet amyloid polypeptides, generates a preferred peptide-binding motif for HLA-DQ8. HLA-DQ8-HIP tetramer+ T cells from the peripheral blood of a T1D patient are characterised by repeated TRBV5 usage, which matches the TCR bias of CD4+ T cells reactive to the HIP peptide isolated from the pancreatic islets of a patient with T1D. The crystal structure of three TRBV5+ TCR-HLA-DQ8-HIP complexes shows that the TRBV5-encoded TCR β-chain forms a common landing pad on the HLA-DQ8 molecule. The N- and C-termini of the HIP is recognised predominantly by the TCR α-chain and TCR β-chain, respectively, in all three TCR ternary complexes. Accordingly, TRBV5 + TCR recognition of HIP peptides might occur via a ‘polarised’ mechanism, whereby each chain within the αβTCR heterodimer recognises distinct origins of the spliced peptide presented by HLA-DQ8.
Opposing roles for striatonigral and striatopallidal neurons in dorsolateral striatum in consolidating new instrumental actions
Authors: Smith Alexander C. W. , Jonkman Sietse , Difeliceantonio Alexandra G. , O’Connor Richard M. , Ghoshal Soham , Romano Michael F. , Everitt Barry J. , Kenny Paul J. 
Published: August 2021

AbstractComparatively little is known about how new instrumental actions are encoded in the brain. Using whole-brain c-Fos mapping, we show that neural activity is increased in the anterior dorsolateral striatum (aDLS) of mice that successfully learn a new lever-press response to earn food rewards. Post-learning chemogenetic inhibition of aDLS disrupts consolidation of the new instrumental response. Similarly, post-learning infusion of the protein synthesis inhibitor anisomycin into the aDLS disrupts consolidation of the new response. Activity of D1 receptor-expressing medium spiny neurons (D1-MSNs) increases and D2-MSNs activity decreases in the aDLS during consolidation. Chemogenetic inhibition of D1-MSNs in aDLS disrupts the consolidation process whereas D2-MSN inhibition strengthens consolidation but blocks the expression of previously learned habit-like responses. These findings suggest that D1-MSNs in the aDLS encode new instrumental actions whereas D2-MSNs oppose this new learning and instead promote expression of habitual actions.
Sympathetic cooling of a trapped proton mediated by an LC circuit
Authors: Bohman M. , Grunhofer V. , Smorra C. , Wiesinger M. , Will C. , Borchert M. J. , Devlin J. A. , Erlewein S. , Fleck M. , Gavranovic S. , Harrington J. , Latacz B. , Mooser A. , Popper D. , Wursten E. , Blaum K. , Matsuda Y. , Ospelkaus C. , Quint W. , Walz J. , Ulmer S. ,   BASE Collaboration
Published: August 2021

AbstractEfficient cooling of trapped charged particles is essential to many fundamental physics experiments1,2, to high-precision metrology3,4 and to quantum technology5,6. Until now, sympathetic cooling has required close-range Coulomb interactions7,8, but there has been a sustained desire to bring laser-cooling techniques to particles in macroscopically separated traps5,9,10, extending quantum control techniques to previously inaccessible particles such as highly charged ions, molecular ions and antimatter. Here we demonstrate sympathetic cooling of a single proton using laser-cooled Be+ ions in spatially separated Penning traps. The traps are connected by a superconducting LC circuit that enables energy exchange over a distance of 9 cm. We also demonstrate the cooling of a resonant mode of a macroscopic LC circuit with laser-cooled ions and sympathetic cooling of an individually trapped proton, reaching temperatures far below the environmental temperature. Notably, as this technique uses only image–current interactions, it can be easily applied to an experiment with antiprotons1, facilitating improved precision in matter–antimatter comparisons11 and dark matter searches12,13.
EEG microstate in obstructive sleep apnea patients
Authors: Xiong Xin , Ren Yuyan , Gao Shenghan , Luo Jianhua , Liao Jiangli , Wang Chunwu , Yi Sanli , Liu Ruixiang , Xiang Yan , He Jianfeng 
Published: August 2021

AbstractObstructive sleep apnea (OSA) is a common sleep respiratory disease. Previous studies have found that the wakefulness electroencephalogram (EEG) of OSA patients has changed, such as increased EEG power. However, whether the microstates reflecting the transient state of the brain is abnormal is unclear during obstructive hypopnea (OH). We investigated the microstates of sleep EEG in 100 OSA patients. Then correlation analysis was carried out between microstate parameters and EEG markers of sleep disturbance, such as power spectrum, sample entropy and detrended fluctuation analysis (DFA). OSA_OH patients showed that the microstate C increased presence and the microstate D decreased presence compared to OSA_withoutOH patients and controls. The fifth microstate E appeared during N1-OH, but the probability of other microstates transferring to microstate E was small. According to the correlation analysis, OSA_OH patients in N1-OH showed that the microstate D was positively correlated with delta power, and negatively correlated with beta and alpha power; the transition probability of the microstate B → C and E → C was positively correlated with alpha power. In other sleep stages, the microstate parameters were not correlated with power, sample entropy and FDA. We might interpret that the abnormal transition of brain active areas of OSA patients in N1-OH stage leads to abnormal microstates, which might be related to the change of alpha activity in the cortex.
Individual and population dietary specialization decline in fin whales during a period of ecosystem shift
Authors: Jory Cabrol , Lesage Véronique , Leclerc Alexandra , Giard Janie , Iverson Sara , Bérubé Martine , Michaud Robert , Nozais Christian 
Published: August 2021

AbstractThis study sought to estimate the effect of an anthropogenic and climate-driven change in prey availability on the degree of individual and population specialization of a large marine predator, the fin whale (Balaenoptera physalus). We examined skin biopsies from 99 fin whales sampled in the St. Lawrence Estuary (Canada) over a nine year period (1998–2006) during which environmental change was documented. We analyzed stable isotope ratios in skin and fatty acid signatures in blubber samples of whales, as well as in seven potential prey species, and diet was quantitatively assessed using Bayesian isotopic models. An abrupt change in fin whale dietary niche coincided with a decrease in biomass of their predominant prey, Arctic krill (Thysanoessaspp.). This dietary niche widening toward generalist diets occurred in nearly 60% of sampled individuals. The fin whale population, typically composed of specialists of either krill or lipid-rich pelagic fishes, shifted toward one composed either of krill specialists or true generalists feeding on various zooplankton and fish prey. This change likely reduced intraspecific competition. In the context of the current “Atlantification” of northern water masses, our findings emphasize the importance of considering individual-specific foraging tactics and not only population or group average responses when assessing population resilience or when implementing conservation measures.
Comparative transcriptomic analysis of SARS-CoV-2 infected cell model systems reveals differential innate immune responses
Authors: Sun Guihua , Cui Qi , Garcia Gustavo , Wang Cheng , Zhang Mingzi , Arumugaswami Vaithilingaraja , Riggs Arthur D. , Shi Yanhong 
Published: August 2021

AbstractThe transcriptome of SARS-CoV-2-infected cells that reflects the interplay between host and virus has provided valuable insights into mechanisms underlying SARS-CoV-2 infection and COVID-19 disease progression. In this study, we show that SARS-CoV-2 can establish a robust infection in HEK293T cells that overexpress human angiotensin-converting enzyme 2 (hACE2) without triggering significant host immune response. Instead, endoplasmic reticulum stress and unfolded protein response-related pathways are predominantly activated. By comparing our data with published transcriptome of SARS-CoV-2 infection in other cell lines, we found that the expression level of hACE2 directly correlates with the viral load in infected cells but not with the scale of immune responses. Only cells that express high level of endogenous hACE2 exhibit an extensive immune attack even with a low viral load. Therefore, the infection route may be critical for the extent of the immune response, thus the severity of COVID-19 disease status.
Investigation of major amino acid residues of anti-norfloxacin monoclonal antibodies responsible for binding with fluoroquinolones
Authors: Boonserm Patamalai , Puthong Songchan , Wichai Thanaporn , Noitang Sajee , Khunrae Pongsak , Sooksai Sarintip , Komolpis Kittinan 
Published: August 2021

AbstractIt is important to understand the amino acid residues that govern the properties of the binding between antibodies and ligands. We studied the binding of two anti-norfloxacins, anti-nor 132 and anti-nor 155, and the fluoroquinolones norfloxacin, enrofloxacin, ciprofloxacin, and ofloxacin. Binding cross-reactivities tested by an indirect competitive enzyme-linked immunosorbent assay indicated that anti-nor 132 (22–100%) had a broader range of cross-reactivity than anti-nor 155 (62–100%). These cross-reactivities correlated with variations in the numbers of interacting amino acid residues and their positions. Molecular docking was employed to investigate the molecular interactions between the fluoroquinolones and the monoclonal antibodies. Homology models of the heavy chain and light chain variable regions of each mAb 3D structure were docked with the fluoroquinolones targeting the crucial part of the complementarity-determining regions. The fluoroquinolone binding site of anti-nor 155 was a region of the HCDR3 and LCDR3 loops in which hydrogen bonds were formed with TYR (H:35), ASN (H:101), LYS (H:106), ASN (L:92), and ASN (L:93). These regions were further away in anti-nor 132 and could not contact the fluoroquinolones. Another binding region consisting of HIS (L:38) and ASP (H:100) was found for norfloxacin, enrofloxacin, and ciprofloxacin, whereas only ASP (H:100) was found for ofloxacin.
Simulation of gas sensing mechanism of porous metal oxide semiconductor sensor based on finite element analysis
Authors: Li Songlin , Zhang Min , Wang Hai 
Published: August 2021

AbstractIn recent years, finite element analysis is increasingly adopted to simulate the mechanism of metal oxide semiconductor (MOS) resistive gas sensors. In this article, the chemical reaction engineering module in the COMSOL Multiphysics tool is used to describe the dynamic equilibrium process of oxygen ions in the sensor. The boundary conditions of temperature transfer, conductivity model, and mass transfer are applied to simulate the convection, diffusion, and penetration processes. The response of the sensor at different temperatures (445 K–521 K) and different target gas concentrations (1–500 ppm) is simulated. In this paper, the dynamic model of oxygen ions is used creatively as a bridge between gas concentration and sensor response instead of the traditional direct parameter fitting method. The simulated result of the surface oxygen ion control and permeability control model of the MOS gas sensor shows a good agreement with the real sensor. For explaining the principle of metal oxide semiconductor gas sensors simulations has been performed on COMSOL Multiphysics software. The proposed method in this paper is based on the underlying transfer logic of the sensor signal, it is expected to predict the sensor signal and assist the sensor design.
Novel metabolomic profile of subjects with non-classic apparent mineralocorticoid excess
Authors: Tapia-Castillo Alejandra , Carvajal Cristian A. , López-Cortés Xaviera , Vecchiola Andrea , Fardella Carlos E. 
Published: August 2021

AbstractNonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n = 28) and healthy controls (n = 27). A discovery study based in untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolomic variations were assayed by principal component analysis and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. A ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-l-glutamyl-l-methionine sulfoxide and 5-sulfoxymethylfurfural, exhibited significant association with cortisone, which are potential biomarkers of NC-AME, however further assays should elucidate its biological role in setup and progression of this phenotype.
Respiratory sound classification for crackles, wheezes, and rhonchi in the clinical field using deep learning
Authors: Kim Yoonjoo , Hyon YunKyong , Jung Sung Soo , Lee Sunju , Yoo Geon , Chung Chaeuk , Ha Taeyoung 
Published: August 2021

AbstractAuscultation has been essential part of the physical examination; this is non-invasive, real-time, and very informative. Detection of abnormal respiratory sounds with a stethoscope is important in diagnosing respiratory diseases and providing first aid. However, accurate interpretation of respiratory sounds requires clinician’s considerable expertise, so trainees such as interns and residents sometimes misidentify respiratory sounds. To overcome such limitations, we tried to develop an automated classification of breath sounds. We utilized deep learning convolutional neural network (CNN) to categorize 1918 respiratory sounds (normal, crackles, wheezes, rhonchi) recorded in the clinical setting. We developed the predictive model for respiratory sound classification combining pretrained image feature extractor of series, respiratory sound, and CNN classifier. It detected abnormal sounds with an accuracy of 86.5% and the area under the ROC curve (AUC) of 0.93. It further classified abnormal lung sounds into crackles, wheezes, or rhonchi with an overall accuracy of 85.7% and a mean AUC of 0.92. On the other hand, as a result of respiratory sound classification by different groups showed varying degree in terms of accuracy; the overall accuracies were 60.3% for medical students, 53.4% for interns, 68.8% for residents, and 80.1% for fellows. Our deep learning-based classification would be able to complement the inaccuracies of clinicians' auscultation, and it may aid in the rapid diagnosis and appropriate treatment of respiratory diseases.
The origin of mechanical harmonic distortion within the organ of Corti in living gerbil cochleae
Authors: He Wenxuan , Ren Tianying 
Published: August 2021

AbstractAlthough auditory harmonic distortion has been demonstrated psychophysically in humans and electrophysiologically in experimental animals, the cellular origin of the mechanical harmonic distortion remains unclear. To demonstrate the outer hair cell-generated harmonics within the organ of Corti, we measured sub-nanometer vibrations of the reticular lamina from the apical ends of the outer hair cells in living gerbil cochleae using a custom-built heterodyne low-coherence interferometer. The harmonics in the reticular lamina vibration are significantly larger and have broader spectra and shorter latencies than those in the basilar membrane vibration. The latency of the second harmonic is significantly greater than that of the fundamental at low stimulus frequencies. These data indicate that the mechanical harmonics are generated by the outer hair cells over a broad cochlear region and propagate from the generation sites to their own best-frequency locations.