bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Model for Predicting Coastal Aerosol Size Distributions in Chinese Seas
Authors: Pan Yue , Cui Shengcheng , Rao Ruizhong 
Published: May 2020

AbstractAerosol is a key factor in the study of interactions between light and radiation. In coastal environments, the diversity and complexity of aerosol components make it difficult to accurately determine their microphysical and optical properties. In this paper, the analysis focuses on the aerosol size distribution (ASD) prediction in the coasts of the South China Sea (SCS, Maoming) and the Yellow Sea (YS, Qingdao). Due to large differences in spatial scale with respect to geographical and meteorological conditions, ASD in Maoming and Qingdao showed large differences. On the basis of Navy Aerosol Model (NAM) and Piazzola et al.'s models, combined with the observation data of Maoming and Qingdao, a coastal aerosol model (CAM) was developed to predict ASD for Chinese coastal environment. The aerosol concentration is calculated by the function of fetch and wind speed. Although the aerosol distributions at the two sites are quite different, the CAM is found to be applicable to both sites. Furthermore, the CAM was used in predicting the ASDs in the SCS against the research ship Shenkuo cruise data. The model results were in agreement with the measured values in coastal zone. The model presented in this work would be a useful tool to model ASDs in Chinese coastal seas.
Effects of Microphysical Processes on the Precipitation Spectrum in a Strongly Forced Environment
Authors: Huang Jin‐De , Wu Chien‐Ming 
Published: May 2020

AbstractThis study investigates the effects of microphysical processes on the precipitation spectrum in a strongly forced environment using the vector vorticity cloud‐resolving model (VVM). Experiments are performed under imposed advective cooling and moistening with two microphysics parameterizations: the predicted particle properties scheme (P3) and Lin scheme (VVM‐Lin). Even though the domain‐averaged precipitation is similar in the two experiments, P3 exhibits stronger extreme precipitation in the spectrum compared with VVM‐Lin. Changes in convective structures are responsible for such a difference. Using the isentropic analyses, we identify that in P3, stronger convective updrafts take place in the high θei regime, where air parcels rarely reach. This is caused by the reduced melting of rimed ice particles for energic parcels. Through defining convective core clouds, the relation between the convective structure on the isentropic diagram and the extreme precipitation can be identified. The shifts toward extreme intensity in the precipitation spectrum suggest that the microphysical processes have significant impacts on the extreme precipitation by the convective core clouds. The treatment of microphysics has significant impacts on the convective structures and then alter the probability of extreme events under the strongly forced environment.
Subsurface Structure at the InSight Landing Site From Compliance Measurements by Seismic and Meteorological Experiments
Authors: Kenda B. , Drilleau M. , Garcia R. F. , Kawamura T. , Murdoch N. , Compaire N. , Lognonné P. , Spiga A. , Widmer‐Schnidrig R. , Delage P. , Ansan V. , Vrettos C. , Rodriguez S. , Banerdt W. B. , Banfield D. , Antonangeli D. , Christensen U. , Mimoun D. , Mocquet A. , Spohn T. 
Published: May 2020

AbstractMeasurements of ground compliance at the InSight landing site—describing the surface response to pressure loading—are obtained from seismic and meteorological data. Compliance observations show an increase with frequency indicating the presence of a stiffer rock layer beneath the exposed regolith. We performed a Markov chain Monte Carlo inversion to investigate the vertical profile of the elastic parameters down to 20 m below InSight. Compliance was inverted both freely and assuming prior knowledge of compaction in the regolith, and the limitations and strengths of the methods were assessed on the basis of theoretical considerations and synthetic tests. The inverted Young modulus exhibits an increase by a factor of 10–100 over the first 10–15 m, compatible with a structural discontinuity between 0.7 and 7 m. The proposed scheme can be used for joint inversion of other seismic, geological, or mechanical constraints to refine the resulting vertical section.
Tanshinone IIA inhibits oral squamous cell carcinoma via reducing Akt-c-Myc signaling-mediated aerobic glycolysis
Authors: Li Ming , Gao Feng , Zhao Qing , Zuo Huilan , Liu Wenbin , Li Wei 
Published: May 2020

AbstractAerobic glycolysis is one of the hallmarks of human cancer cells. Overexpression of hexokinase 2 (HK2) plays a crucial role in the maintaining of unlimited tumor cell growth. In the present study, we found that the oral squamous cell carcinoma (OSCC) cells exhibited an aerobic glycolysis phenotype. Moreover, HK2 is highly expressed in OSCC patient derived-tissues and cell lines. Depletion of HK2 inhibited OSCC cell growth in vitro and in vivo. With a natural product screening, we identified Tanshinone IIA (Tan IIA) as a potential anti-tumor compound for OSCC through suppressing HK2-mediated glycolysis. Tan IIA decreased glucose consumption, lactate production, and promoted intrinsic apoptosis in OSCC cells. The mechanism study revealed that Tan IIA inhibited the Akt-c-Myc signaling and promoted E3 ligase FBW7-mediated c-Myc ubiquitination and degradation, which eventually reduced HK2 expression at the transcriptional level. In summary, these results indicate that targeting HK2-mediated aerobic glycolysis is a promising anti-tumor strategy for OSCC treatment.
Neutrophils undergo switch of apoptosis to NETosis during murine fatty liver injury via S1P receptor 2 signaling
Authors: Zhao Xinhao , Yang Le , Chang Na , Hou Lei , Zhou Xuan , Yang Lin , Li Liying 
Published: May 2020

AbstractInappropriate neutrophil infiltration and subsequent neutrophil extracellular trap (NET) formation have been confirmed to be involved in chronic inflammatory conditions. Fatty liver disease is an increasingly severe health problem worldwide and currently considered the most common cause of chronic liver disease. Sphingosine 1-phosphate (S1P), a product of membrane sphingolipid metabolism, regulates vital physiological and pathological actions by inducing infiltration and activation of various cell types through S1P receptors (S1PRs). Here, we seek to determine the S1PR-mediated effects on neutrophil activation during chronic liver inflammation. In this study, NETs are detected in the early stage of methionine-choline-deficient and a high-fat (MCDHF) diet-induced liver injury. NET depletion by deoxyribonuclease I intraperitoneal injection significantly protects liver from MCDHF-induced liver injury in vivo. Meanwhile, we show that levels of myeloperoxidase-DNA complex (NET marker) in the serum present positive correlation with sphingosine kinase1 (S1P rate-limiting enzyme) messenger RNA expression or S1P levels in the injured liver of MCDHF-fed mice. In vitro, S1PR2 participates in the redirection of neutrophil apoptosis to NETosis via Gαi/o, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and reactive oxygen species signaling pathways. Moreover, S1PR2 knockdown in MCDHF-fed mice by S1PR2-siRNA intravenous injection significantly inhibits NET formation in damaged liver tissue and then alleviates hepatic inflammation and fibrosis. Conclusion: In the early stage of fatty liver disease, S1PR2-mediated neutrophil activation plays an important role in the evolvement of liver injury.
BCL-xL/BCL2L1 is a critical anti-apoptotic protein that promotes the survival of differentiating pancreatic cells from human pluripotent stem cells
Authors: Loo Larry Sai Weng , Soetedjo Andreas Alvin Purnomo , Lau Hwee Hui , Ng Natasha Hui Jin , Ghosh Soumita , Nguyen Linh , Krishnan Vidhya Gomathi , Choi Hyungwon , Roca Xavier , Hoon Shawn , Teo Adrian Kee Keong 
Published: May 2020

AbstractThe differentiation of human pluripotent stem cells into pancreatic cells involves cellular proliferation and apoptosis during cell fate transitions. However, their implications for establishing cellular identity are unclear. Here, we profiled the expression of BCL-2 family of proteins during pancreatic specification and observed an upregulation of BCL-xL, downregulation of BAK and corresponding downregulation of cleaved CASP3 representative of apoptosis. Experimental inhibition of BCL-xL reciprocally increased apoptosis and resulted in a decreased gene expression of pancreatic markers despite a compensatory increase in anti-apoptotic protein BCL-2. RNA-Seq analyses then revealed a downregulation of multiple metabolic genes upon inhibition of BCL-xL. Follow-up bioenergetics assays revealed broad downregulation of both glycolysis and oxidative phosphorylation when BCL-xL was inhibited. Early perturbation of BCL-xL during pancreatic specification also had subsequent detrimental effects on the formation of INS+ pancreatic beta-like cells. In conclusion, the more differentiated pancreatic progenitors are dependent on anti-apoptotic BCL-xL for survival, whereas the less differentiated pancreatic progenitors that survived after WEHI-539 treatment would exhibit a more immature phenotype. Therefore, modulation of the expression level of BCL-xL can potentially increase the survival and robustness of pancreatic progenitors that ultimately define human pancreatic beta cell mass and function.
Functionally distinct high and low theta oscillations in the human hippocampus
Authors: Goyal Abhinav , Miller Jonathan , Qasim Salman E. , Watrous Andrew J. , Zhang Honghui , Stein Joel M. , Inman Cory S. , Gross Robert E. , Willie Jon T. , Lega Bradley , Lin Jui-Jui , Sharan Ashwini , Wu Chengyuan , Sperling Michael R. , Sheth Sameer A. , McKhann Guy M. , Smith Elliot H. , Schevon Catherine , Jacobs Joshua 
Published: May 2020

AbstractBased on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4–10 Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta’s function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior–posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.
Accurate deep neural network inference using computational phase-change memory
Authors: Joshi Vinay , Le Gallo Manuel , Haefeli Simon , Boybat Irem , Nandakumar S. R. , Piveteau Christophe , Dazzi Martino , Rajendran Bipin , Sebastian Abu , Eleftheriou Evangelos 
Published: May 2020

AbstractIn-memory computing using resistive memory devices is a promising non-von Neumann approach for making energy-efficient deep learning inference hardware. However, due to device variability and noise, the network needs to be trained in a specific way so that transferring the digitally trained weights to the analog resistive memory devices will not result in significant loss of accuracy. Here, we introduce a methodology to train ResNet-type convolutional neural networks that results in no appreciable accuracy loss when transferring weights to phase-change memory (PCM) devices. We also propose a compensation technique that exploits the batch normalization parameters to improve the accuracy retention over time. We achieve a classification accuracy of 93.7% on CIFAR-10 and a top-1 accuracy of 71.6% on ImageNet benchmarks after mapping the trained weights to PCM. Our hardware results on CIFAR-10 with ResNet-32 demonstrate an accuracy above 93.5% retained over a one-day period, where each of the 361,722 synaptic weights is programmed on just two PCM devices organized in a differential configuration.
Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor
Authors: Guan Chengcheng , Niu Yange , Chen Si-Cong , Kang Yunlu , Wu Jing-Xiang , Nishi Koji , Chang Catherine C. Y. , Chang Ta-Yuan , Luo Tuoping , Chen Lei 
Published: May 2020

AbstractSterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage. SOAT1 is a target to treat several human diseases. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 Å resolution reveals that a small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design targeting hSOAT1 and other mammalian MBOAT family members.
The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice
Authors: Yoshida Shota , Nakagami Hironori , Hayashi Hiroki , Ikeda Yuka , Sun Jiao , Tenma Akiko , Tomioka Hideki , Kawano Tomohiro , Shimamura Munehisa , Morishita Ryuichi , Rakugi Hiromi 
Published: May 2020

AbstractSenotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells, defined as CD4+ CD44high CD62Llow PD-1+ CD153+ cells, accumulate in visceral adipose tissues (VAT) in obese individuals. Here, we show the long-lasting effect of using CD153 vaccination to remove senescent T cells from high-fat diet (HFD)-induced obese C57BL/6J mice. We administered a CD153 peptide-KLH (keyhole limpet hemocyanin) conjugate vaccine with Alhydrogel (CD153-Alum) or CpG oligodeoxynucleotide (ODN) 1585 (CD153-CpG) and confirmed an increase in anti-CD153 antibody levels that was sustained for several months. After being fed a HFD for 10–11 weeks, adipose senescent T cell accumulation was significantly reduced in the VAT of CD153-CpG-vaccinated mice, accompanied by glucose tolerance and insulin resistance. A complement-dependent cytotoxicity (CDC) assay indicated that the mouse IgG2 antibody produced in the CD153-CpG-vaccinated mice successfully reduced the number of senescent T cells. The CD153-CpG vaccine is an optional tool for senolytic therapy.
Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma
Authors: Thurner Lorenz , Hartmann Sylvia , Fadle Natalie , Regitz Evi , Kemele Maria , Kim Yoo-Jin , Bohle Rainer Maria , Nimmesgern Anna , von Müller Lutz , Kempf Volkhard A. J. , Weniger Marc A. , Neumann Frank , Schneider Nadine , Vornanen Martine , Sundström Christer , de Leval Laurence , Engert Andreas , Eichenauer Dennis A. , Küppers Ralf , Preuss Klaus-Dieter , Hansmann Martin-Leo , Pfreundschuh Michael 
Published: May 2020

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta’ (RpoC) fromMoraxella catarrhalisas frequent antigen of BCRs of IgD+LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/κ-type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed byMoraxella catarrhalisthat is known to activate IgD+B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-κB pathway and the proliferation of IgD+DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD+BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies.
The genome of Mekong tiger perch (Datnioides undecimradiatus) provides insights into the phylogenetic position of Lobotiformes and biological conservation
Authors: Sun Shuai , Wang Yue , Zeng Wenhong , Du Xiao , Li Lei , Hong Xiaoning , Huang Xiaoyun , Zhang He , Zhang Mengqi , Fan Guangyi , Liu Xin , Liu Shanshan 
Published: May 2020

AbstractMekong tiger perch (Datnioides undecimradiatus) is an ornamental and vulnerable freshwater fish native to the Mekong basin in Indochina, belonging to the order Lobotiformes. Here, we generated 121X stLFR co-barcode clean reads and 18X Oxford Nanopore MinION reads and obtained a 595 Mb Mekong tiger perch genome, which is the first whole genome sequence in the order Lobotiformes. Based on this genome, the phylogenetic tree analysis suggested that Lobotiformes is more closely related to Sciaenidae than to Tetraodontiformes, resolving a long-time dispute. We depicted the genes involved in pigment development in Mekong tiger perch and results confirmed that the four rate-limiting genes of pigment synthesis had been retained after fish-specific genome duplication. We also estimated the demographic history of Mekong tiger perch, which showed that the effective population size suffered a continuous reduction possibly related to the contraction of immune-related genes. Our study provided a reference genome resource for the Lobotiformes, as well as insights into the phylogenetic position of Lobotiformes and biological conservation.
Re-estimation improved the performance of two Framingham cardiovascular risk equations and the Pooled Cohort equations: A nationwide registry analysis
Authors: Wallisch Christine , Heinze Georg , Rinner Christoph , Mundigler Gerald , Winkelmayer Wolfgang C. , Dunkler Daniela 
Published: May 2020

AbstractEquations predicting the risk of occurrence of cardiovascular disease (CVD) are used in primary care to identify high-risk individuals among the general population. To improve the predictive performance of such equations, we updated the Framingham general CVD 1991 and 2008 equations and the Pooled Cohort equations for atherosclerotic CVD within five years in a contemporary cohort of individuals who participated in the Austrian health-screening program from 2009–2014. The cohort comprised 1.7 M individuals aged 30–79 without documented CVD history. CVD was defined by hospitalization or death from cardiovascular cause. Using baseline and follow-up data, we recalibrated and re-estimated the equations. We evaluated the gain in discrimination and calibration and assessed explained variation. A five-year general CVD risk of 4.61% was observed. As expected, discrimination c-statistics increased only slightly and ranged from 0.73–0.79. The two original Framingham equations overestimated the CVD risk, whereas the original Pooled Cohort equations underestimated it. Re-estimation improved calibration of all equations adequately, especially for high-risk individuals. Half of the individuals were reclassified into another risk category using the re-estimated equations. Predictors in the re-estimated Framingham equations explained 7.37% of the variation, whereas the Pooled Cohort equations explained 5.81%. Age was the most important predictor.
Venturicidin A, A Membrane-active Natural Product Inhibitor of ATP synthase Potentiates Aminoglycoside Antibiotics
Authors: Yarlagadda Venkateswarlu , Medina Ricardo , Wright Gerard D. 
Published: May 2020

AbstractDespite the remarkable advances due to the discovery and development of antimicrobials agents, infectious diseases remain the second leading cause of death worldwide. This fact underlines the importance of developing new therapeutic strategies to address the widespread antibiotic resistance, which is the major contributing factor for clinical failures of the current therapeutics. In a screen for antibiotic adjuvants, we identified a natural product from actinomycetes, venturicidin A (VentA), that potentiates the aminoglycoside antibiotic gentamicin against multidrug-resistant clinical isolates of Staphylococcus, Enterococcus, and Pseudomonas aeruginosa. Furthermore, the combination of gentamicin and VentA was bactericidal and rapidly eradicated methicillin-resistant S. aureus (MRSA). The molecular mechanism of gentamicin potentiation activity is attributed to uncoupling of ATP synthesis by VentA from electron transport presumably by blocking the proton flow through ATP synthase, which results in an elevated concentration of extracellular protons and subsequent anticipated raise in gentamicin uptake. The disruption of the proton flux was characterized by perturbed membrane potential in MRSA. These results demonstrate that inhibition of ATP synthase along with the subsequent membrane dysregulation, as shown here with VentA, complements aminoglycoside antibiotics against MDR bacteria, and that this approach may be employed to combat bacterial resistance.
Synergistic depletion of gut microbial consortia, but not individual antibiotics, reduces amyloidosis in APPPS1-21 Alzheimer’s transgenic mice
Authors: Dodiya Hemraj B. , Frith Mary , Sidebottom Ashley , Cao Yajun , Koval Jason , Chang Eugene , Sisodia Sangram S. 
Published: May 2020

AbstractIn preceding efforts, we demonstrated that antibiotic (ABX) cocktail-mediated perturbations of the gut microbiome in two independent transgenic lines, termed APPSWE/PS1ΔE9 and APPPS1-21, leads to a reduction in Aβ deposition in male mice. To determine whether these observed reductions of cerebral Aβ amyloidosis are specific to any individual antibiotic or require the synergistic effects of several antibiotics, we treated male APPPS1-21 transgenic mice with either individual ABX or an ABX cocktail and assessed amyloid deposition. Specifically, mice were subject to oral gavage with high dose kanamycin, gentamicin, colistin, metronidazole, vancomycin, individually or in a combination (ABX cocktail) from postnatal days (PND) 14 to 21, followed by ad libitum, low-dose individual ABX or ABX cocktail in the drinking water until the time of sacrifice. A control group was subject to gavage with water from PND 14 to 21 and received drinking water till the time of sacrifice. At the time of sacrifice, all groups showed distinct cecal microbiota profiles with the highest differences between control and ABX cocktail-treated animals. Surprisingly, only the ABX cocktail significantly reduced brain Aβ amyloidosis compared to vehicle-treated animals. In parallel studies, and to assess the potential exposure of ABX to the brain, we quantified the levels of each ABX in the brain by liquid chromatography-mass spectrometry (LC-MS) at PND 22 or at 7 weeks of age. With the exception of metronidazole (which was observed at less than 3% relative to the spiked control brains), we were unable to detect the other individual ABX in brain homogenates. Our findings suggest that synergistic alterations of gut microbial consortia, rather than individual antimicrobial agents, underlie the observed reductions in brain amyloidosis.