bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emulating synaptic response in n- and p-channel MoS2 transistors by utilizing charge trapping dynamics
Authors: Bhattacharjee Shubhadeep , Wigchering Rient , Manning Hugh G. , Boland John. J. , Hurley Paul K. 
Published: July 2020

AbstractBrain-inspired, neuromorphic computing aims to address the growing computational complexity and power consumption in modern von-Neumann architectures. Progress in this area has been hindered due to the lack of hardware elements that can mimic neuronal/synaptic behavior which form the fundamental building blocks for spiking neural networks (SNNs). In this work, we leverage the short/long term memory effects due to the electron trapping events in an atomically thin channel transistor that mimic the exchange of neurotransmitters and emulate a synaptic response. Re-doped (n-type) and Nb-doped (p-type) molybdenum di-sulfide (MoS2) field-effect transistors are examined using pulsed-gate measurements, which identify the time scales of electron trapping/de-trapping. The devices demonstrate promising trends for short/long term plasticity in the order of ms/minutes, respectively. Interestingly, pulse paired facilitation (PPF), which quantifies the short-term plasticity, reveal time constants (τ1 = 27.4 ms, τ2 = 725 ms) that closely match those from a biological synapse. Potentiation and depression measurements describe the ability of the synaptic device to traverse several analog states, where at least 50 conductance values are accessed using consecutive pulses of equal height and width. Finally, we demonstrate devices, which can emulate a well-known learning rule, spike time-dependent plasticity (STDP) which codifies the temporal sequence of pre- and post-synaptic neuronal firing into corresponding synaptic weights. These synaptic devices present significant advantages over iontronic counterparts and are envisioned to create new directions in the development of hardware for neuromorphic computing.
The hot sites of α-synuclein in amyloid fibril formation
Authors: Khammari Anahita , Arab Seyed Shahriar , Ejtehadi Mohammad Reza 
Published: July 2020

AbstractThe role of alpha-synuclein (αS) amyloid fibrillation has been recognized in various neurological diseases including Parkinson’s Disease (PD). In early stages, fibrillation occurs by the structural transition from helix to extended states in monomeric αS followed by the formation of beta-sheets. This alpha-helix to beta-sheet transition (αβT) speeds up the formation of amyloid fibrils through the formation of unstable and temporary configurations of the αS. In this study, the most important regions that act as initiating nuclei and make unstable the initial configuration were identified based on sequence and structural information. In this regard, a Targeted Molecular Dynamics (TMD) simulation was employed using explicit solvent models under physiological conditions. Identified regions are those that are in the early steps of structural opening. The trajectory was clustered the structures characterized the intermediate states. The findings of this study would help us to better understanding of the mechanism of amyloid fibril formation.
Hyperglycemia-stimulating diet induces liver steatosis in sheep
Authors: Kalyesubula Mugagga , Mopuri Ramgopal , Rosov Alexander , Alon Tamir , Edery Nir , Moallem Uzi , Dvir Hay 
Published: July 2020

AbstractHepatic steatosis is strongly associated with chronic liver disease and systemic metabolic disorder. Adipose lipolysis is a recognized principal source of intrahepatic fat in various metabolic disorders, including non-alcoholic fatty liver disease. We hypothesized that, in the premorbid state, hepatic de novo lipogenesis (DNL) driven by excess carbohydrates abundance might play a more significant role. We employed a novel nutritional model in sheep of two distinct carbohydrates abundances. During 4 months of the dietary treatment, lambs were monitored for metabolic and terminal liver parameters. Lambs grown on the high-calorie (HC) diet were consistently more hyperglycemic and hyperinsulinemic than lambs grown on the lower-calorie (LC) diet (P < 0.0001). As a result, the HC lambs developed systemic- (HOMA-IR of 7.3 vs. 3.1; P < 0.0001), and adipose- (ADIPO-IR of 342.7 vs. 74.4; P < 0.0001) insulin resistance, significant adiposity (P < 0.0001), and higher plasma triglycerides (P < 0.05). Circulating leukocytes in the HC lambs had higher mRNA expression levels of the proinflammatory markers CCL2 (P < 0.01) and TNF-alpha (P < 0.04), and IL1B trended higher (P < 0.1). Remarkably, lambs on the HC diet developed substantial liver steatosis (mean fat content of 8.1 vs. 5.3% in the LC group; P < 0.0001) with a higher histological steatosis score (2.1 vs. 0.4; P < 0.0002). Hepatic steatosis was most-strongly associated with blood glucose and insulin levels but negatively correlated with circulating fatty acids—indicating a more significant contribution from hepatic DNL than from adipose lipolysis. Sheep may prove an attractive large-animal model of fatty liver and metabolic comorbidities resulting from excess carbohydrate-based energy early in life.
A pooled genome-wide screening strategy to identify and rank influenza host restriction factors in cell-based vaccine production platforms
Authors: Sharon David M. , Nesdoly Sean , Yang Hsin J. , Gélinas Jean-François , Xia Yu , Ansorge Sven , Kamen Amine A. 
Published: July 2020

AbstractCell-derived influenza vaccines provide better protection and a host of other advantages compared to the egg-derived vaccines that currently dominate the market, but their widespread use is hampered by a lack of high yield, low cost production platforms. Identification and knockout of innate immune and metabolic restriction factors within relevant host cell lines used to grow the virus could offer a means to substantially increase vaccine yield. In this paper, we describe and validate a novel genome-wide pooled CRISPR/Cas9 screening strategy that incorporates a reporter virus and a FACS selection step to identify and rank restriction factors in a given vaccine production cell line. Using the HEK-293SF cell line and A/PuertoRico/8/1934 H1N1 influenza as a model, we identify 64 putative influenza restriction factors to direct the creation of high yield knockout cell lines. In addition, gene ontology and protein complex enrichment analysis of this list of putative restriction factors offers broader insights into the primary host cell determinants of viral yield in cell-based vaccine production systems. Overall, this work will advance efforts to address the public health burden posed by influenza.
Trisk 95 as a novel skin mirror for normal and diabetic systemic glucose level
Authors: Ali Nsrein , Rezvani Hamid Reza , Motei Diana , Suleman Sufyan , Mahfouf Walid , Marty Isabelle , Ronkainen Veli-Pekka , Vainio Seppo J. 
Published: July 2020

AbstractDeveloping trustworthy, cost effective, minimally or non-invasive glucose sensing strategies is of great need for diabetic patients. In this study, we used an experimental type I diabetic mouse model to examine whether the skin would provide novel means for identifying biomarkers associated with blood glucose level. We first showed that skin glucose levels are rapidly influenced by blood glucose concentrations. We then conducted a proteomic screen of murine skin using an experimental in vivo model of type I diabetes and wild-type controls. Among the proteins that increased expression in response to high blood glucose, Trisk 95 expression was significantly induced independently of insulin signalling. A luciferase reporter assay demonstrated that the induction of Trisk 95 expression occurs at a transcriptional level and is associated with a marked elevation in the Fluo-4AM signal, suggesting a role for intracellular calcium changes in the signalling cascade. Strikingly, these changes lead concurrently to fragmentation of the mitochondria. Moreover, Trisk 95 knockout abolishes both the calcium flux and the mitochondrial phenotype changes indicating dependency of glucose flux in the skin on Trisk 95 function. The data demonstrate that the skin reacts robustly to systemic blood changes, and that Trisk 95 is a promising biomarker for a glucose monitoring assembly.
Gene mapping and functional annotation of GWAS of oral ulcers using FUMA software
Authors: Jin Xiaoye , Wang Yijie , Zhang Xingru , Zhang Wenqing , Wang Hongdan , Chen Chuanliang 
Published: July 2020

AbstractOral ulcers not only influence the physical health of patients, but they also interfere with their quality of life. However, the exact etiology of oral ulcers is not clear. To explore the roles of genetic factors in oral ulcers, a genome-wide association study of the condition in European individuals was re-evaluated by the FUMA v1.3.5e online tool. A total of 380 independent significant single nucleotide polymorphisms (SNPs) and 89 lead SNPs were identified in 34 genomic risk loci. Out of these identified genomic risk loci, 280 possible causal genes were pinpointed by positional mapping and expression quantitative trait locus mapping. Among these genes, 216 novel genes were identified. Furthermore, some genomic loci were mapped to a single gene. Functional annotation of these prioritized genes revealed that the immune response pathway was implicated in the onset of oral ulcers. Overall, our findings revealed novel possible causal genes and demonstrated that the immune response has a crucial role in the occurrence of oral ulcers.
Iron acquisition system of Sphingobium sp. strain SYK-6, a degrader of lignin-derived aromatic compounds
Authors: Fujita Masaya , Sakumoto Taichi , Tanatani Kenta , Yu HongYang , Mori Kosuke , Kamimura Naofumi , Masai Eiji 
Published: July 2020

AbstractIron, an essential element for all organisms, acts as a cofactor of enzymes in bacterial degradation of recalcitrant aromatic compounds. The bacterial family, Sphingomonadaceae comprises various degraders of recalcitrant aromatic compounds; however, little is known about their iron acquisition system. Here, we investigated the iron acquisition system in a model bacterium capable of degrading lignin-derived aromatics, Sphingobium sp. strain SYK-6. Analyses of SYK-6 mutants revealed that FiuA (SLG_34550), a TonB-dependent receptor (TBDR), was the major outer membrane iron transporter. Three other TBDRs encoded by SLG_04340, SLG_04380, and SLG_10860 also participated in iron uptake, and tonB2 (SLG_34540), one of the six tonB comprising the Ton complex which enables TBDR-mediated transport was critical for iron uptake. The ferrous iron transporter FeoB (SLG_36840) played an important role in iron uptake across the inner membrane. The promoter activities of most of the iron uptake genes were induced under iron-limited conditions, and their regulation is controlled by SLG_29410 encoding the ferric uptake regulator, Fur. Although feoB, among all the iron uptake genes identified is highly conserved in Sphingomonad strains, the outer membrane transporters seem to be diversified. Elucidation of the iron acquisition system promises better understanding of the bacterial degradation mechanisms of aromatic compounds.
Insulin2Q104del (Kuma) mutant mice develop diabetes with dominant inheritance
Authors: Sakano Daisuke , Inoue Airi , Enomoto Takayuki , Imasaka Mai , Okada Seiji , Yokota Mutsumi , Koike Masato , Araki Kimi , Kume Shoen 
Published: July 2020

AbstractInsulin gene mutations have been identified to cause monogenic diabetes, and most of which developed permanent neonatal diabetes at young ages before 6 months of age in humans. To establish an animal model of permanent diabetes, we performed genome editing using the CRISPR/Cas9 system. We generated a novel Kuma mutant mice with p.Q104del in the Insulin2 (Ins2) gene in a BRJ background that exhibits a severe immune deficiency. Kuma mutant mice are non-obese and developed hyperglycemia from 3 weeks after birth in both males and females, which are inherited in a dominant mode. Kuma mutant mice displayed reduced insulin protein levels from 3-weeks-old, which seem to be caused by the low stability of the mutant insulin protein. Kuma mutant showed a reduction in islet size and islet mass. Electron microscopic analysis revealed a marked decrease in the number and size of insulin granules in the beta-cells of the mutant mice. Hyperglycemia of the mutant can be rescued by insulin administration. Our results present a novel insulin mutation that causes permanent early-onset diabetes, which provides a model useful for islet transplantation studies.
Effects of cardiovascular medications on primary patency of hemodialysis arteriovenous fistula
Authors: Chang Te-I. , Chen Cheng-Hsien , Hsieh Hui-Ling , Chen Chun-You , Hsu Shih-Chang , Cheng Ho-Shun , Huang Wen-Cheng , Sue Yuh-Mou , Hsu Yung-Ho , Lin Feng-Yen , Shih Chun-Ming , Lin Shing-Jong , Huang Po-Hsun , Liu Chung-Te 
Published: July 2020

AbstractWhile the patency of vascular access is essential for hemodialysis patients, optimal pharmaceutical treatment to maintain arteriovenous fistula (AVF) patency remains lacking. As cardiovascular diseases are highly prevalent in patients with end-stage renal disease, various cardiovascular medications have also been used to maintain AVF patency. However, previous studies revealed inconsistent therapeutic effects and a comprehensive evaluation of this issue is needed. The present retrospective, longitudinal cohort study included patients receiving successful AVF creation. The evaluated cardiovascular medications included antiplatelet agents, antihypertensive agents, nitrates and nitrites, statins, dipyridamole, and pentoxifylline. The outcome was AVF primary patency. All laboratory data and medication profiles were recorded at baseline and followed at 3-month interval, until the end of the 2-year study period. Cox proportional regression model with time-dependent covariates was used to evaluate the risk for AVF patency loss. A total of 349 patients were included in the present study, in which 57% were men and the mean age was 65 ± 14 years. Among the included patients, 40% used antiplatelet agents, 27% used dipyridamole and 36% used statins at baseline. Of all the evaluated cardiovascular medications, only dipyridamole showed significant association with a higher risk for loss of AVF patency. To evaluate the effect of combination of antiplatelet agents and dipyridamole, the patients were classified into four groups, I: combine use of antiplatelet agents and dipyridamole, II: antiplatelet only, III: dipyridamole only; IV: none of both were used. Of the four groups, group IV exhibited highest AVF patency (52.4%), which was followed by group III (42.7%), group II (40%), and group I (28.6%), respectively. Compared with group IV, only group I showed a significantly higher risk for AVF patency loss. None of the cardiovascular medications evaluated in the present study showed a beneficial effect on AVF patency. Furthermore, dipyridamole showed an association with a higher risk of AVF patency loss. We do not suggest a beneficial effect of dipyridamole on maintaining AVF patency, particularly in combination with antiplatelet agents.
Physical interpretation of shear-rate behaviour of soils and geotechnical solution to the coefficient of start-up friction with low inertial number
Authors: Fei Jianbo , Jie Yuxin , Sun Xiaohui , Xiong Hao 
Published: July 2020

AbstractShear experiments on soils have revealed the effects of shear rate, confining pressure, and grain size on the residual shear strength, but their nature is not well understood. To interpret these behaviours, a single dimensionless inertial number I from granular physics is introduced. A linear relationship between coefficient of residual friction μr and the natural logarithm of I was found by analysing geotechnical test data from other literature and helps to resolve the μ(aI)-rheology, which was proved invalid in the quasi-static regime. A method is proposed that introduces two three-dimensional yield criteria for soils to classify the frictional properties between grains in the quasi-static regime. The empirical coefficient of start-up friction is replaced by strength parameters of the soil. When compliant with the Mohr–Coulomb yield criterion, this coefficient is positively correlated with the internal angle of friction but negatively correlated with the Lode angle. Moreover from further analysis, the calculated strength is smallest in the pure tension state, largest in the pure compression state, and intermediate in the pure shearing state. This result is consistent with the properties of compressive endurable and tensive intolerable for natural geomaterials.
Ultralow power spin–orbit torque magnetization switching induced by a non-epitaxial topological insulator on Si substrates
Authors: Khang Nguyen Huynh Duy , Nakano Soichiro , Shirokura Takanori , Miyamoto Yasuyoshi , Hai Pham Nam 
Published: July 2020

AbstractThe large spin Hall effect in topological insulators (TIs) is very attractive for ultralow-power spintronic devices. However, evaluation of the spin Hall angle and spin–orbit torque (SOT) of TIs is usually performed on high-quality single-crystalline TI thin films grown on dedicated III-V semiconductor substrates. Here, we report on room-temperature ultralow power SOT magnetization switching of a ferrimagnetic layer by non-epitaxial BiSb TI thin films deposited on Si/SiO2 substrates. We show that non-epitaxial BiSb thin films outperform heavy metals and other epitaxial TI thin films in terms of the effective spin Hall angle and switching current density by one to nearly two orders of magnitude. The critical SOT switching current density in BiSb is as low as 7 × 104 A/cm2 at room temperature. The robustness of BiSb against crystal defects demonstrate its potential applications to SOT-based spintronic devices.
Altered active control of step width in response to mediolateral leg perturbations while walking
Authors: Reimold Nicholas K. , Knapp Holly A. , Henderson Rachel E. , Wilson Landi , Chesnutt Alyssa N. , Dean Jesse C. 
Published: July 2020

AbstractDuring human walking, step width is predicted by mediolateral motion of the pelvis, a relationship that can be attributed to a combination of passive body dynamics and active sensorimotor control. The purpose of the present study was to investigate whether humans modulate the active control of step width in response to a novel mechanical environment. Participants were repeatedly exposed to a force-field that either assisted or perturbed the normal relationship between pelvis motion and step width, separated by washout periods to detect the presence of potential after-effects. As intended, force-field assistance directly strengthened the relationship between pelvis displacement and step width. This relationship remained strengthened with repeated exposure to assistance, and returned to baseline afterward, providing minimal evidence for assistance-driven changes in active control. In contrast, force-field perturbations directly weakened the relationship between pelvis motion and step width. Repeated exposure to perturbations diminished this negative direct effect, and produced larger positive after-effects once the perturbations ceased. These results demonstrate that targeted perturbations can cause humans to adjust the active control that contributes to fluctuations in step width.
11-Deoxycortisol controls hydromineral balance in the most basal osmoregulating vertebrate, sea lamprey (Petromyzon marinus)
Authors: Shaughnessy Ciaran A. , Barany Andre , McCormick Stephen D. 
Published: July 2020

AbstractIt is unknown whether and how osmoregulation is controlled by corticosteroid signaling in the phylogenetically basal vertebrate group Agnatha, including lampreys and hagfishes. It is known that a truncated steroid biosynthetic pathway in lampreys produces two predominant circulating corticosteroids, 11-deoxycortisol (S) and 11-deoxycorticosterone (DOC). Furthermore, lampreys express only a single, ancestral corticosteroid receptor (CR). Whether S and/or DOC interact with the CR to control osmoregulation in lampreys is still unknown. We examined the role of the endogenous corticosteroids in vivo and ex vivo in sea lamprey (Petromyzon marinus) during the critical metamorphic period during which sea lamprey increase osmoregulatory capacity and acquire seawater (SW) tolerance. We demonstrate in vivo that increases in circulating [S] and gill CR abundance are associated with increases in osmoregulatory capacity during metamorphosis. We further show that in vivo and ex vivo treatment with S increases activity and expression of gill active ion transporters and improves SW tolerance, and that only S (and not DOC) has regulatory control over active ion transport in the gills. Lastly, we show that the lamprey CR expresses an ancestral, spironolactone-as-agonist structural motif and that spironolactone treatment in vivo increases osmoregulatory capacity. Together, these results demonstrate that S is an osmoregulatory hormone in lamprey and that receptor-mediated discriminative corticosteroid regulation of hydromineral balance is an evolutionarily basal trait among vertebrates.
Racial/ethnic and geographic differences in polybrominated diphenyl ether (PBDE) levels across maternal, placental, and fetal tissues during mid-gestation
Authors: Varshavsky Julia R. , Sen Saunak , Robinson Joshua F. , Smith Sabrina Crispo , Frankenfield Julie , Wang Yunzhu , Yeh Greg , Park June-Soo , Fisher Susan J. , Woodruff Tracey J. 
Published: July 2020

AbstractPrenatal polybrominated diphenyl ether (PBDE) exposures are a public health concern due to their persistence and potential for reproductive and developmental harm. However, we have little information about the extent of fetal exposures during critical developmental periods and the variation in exposures for groups that may be more highly exposed, such as communities of color and lower socioeconomic status (SES). To characterize maternal–fetal PBDE exposures among potentially vulnerable groups, PBDE levels were examined in the largest sample of matched maternal serum, placenta, and fetal liver tissues during mid-gestation among a geographically, racially/ethnically, and socially diverse population of pregnant women from Northern California and the Central Valley (n = 180; 2014–16). Maternal–fetal PBDE levels were compared to population characteristics using censored Kendall’s tau correlation and linear regression. PBDEs were commonly detected in all biomatrices. Before lipid adjustment, wet-weight levels of all four PBDE congeners were highest in the fetal liver (p < 0.001), whereas median PBDE levels were significantly higher in maternal serum than in the fetal liver or placenta after lipid-adjustment (p < 0.001). We also found evidence of racial/ethnic disparities in PBDE exposures (Non-Hispanic Black > Latina/Hispanic > Non-Hispanic White > Asian/Pacific Islander/Other; p < 0.01), with higher levels of BDE-100 and BDE-153 among non-Hispanic Black women compared to the referent group (Latina/Hispanic women). In addition, participants living in Fresno/South Central Valley had 34% (95% CI: − 2.4 to 84%, p = 0.07) higher wet-weight levels of BDE-47 than residents living in the San Francisco Bay Area. PBDEs are widely detected and differentially distributed in maternal–fetal compartments. Non-Hispanic Black pregnant women and women from Southern Central Valley geographical populations may be more highly exposed to PBDEs. Further research is needed to identify sources that may be contributing to differential exposures and associated health risks among these vulnerable populations.