bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutamine deprivation triggers NAGK-dependent hexosamine salvage
Authors: Campbell Sydney L. , Mesaros Clementina , Izzo Luke , Affronti Hayley , Noji Michael , Schaffer Bethany E. , Tsang Tiffany , Sun Kathryn , Trefely Sophie , Kruijning Salisa , Blenis John , Blair Ian A. , Wellen Kathryn E. 
Published: September 2020

AbstractTumors frequently exhibit aberrant glycosylation, which can impact cancer progression and therapeutic responses. The hexosamine biosynthesis pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a major substrate for glycosylation in the cell. Prior studies have identified the HBP as a promising therapeutic target in pancreatic ductal adenocarcinoma (PDA). The HBP requires both glucose and glutamine for its initiation. The PDA tumor microenvironment is nutrient poor, however, prompting us to investigate how nutrient limitation impacts hexosamine synthesis. Here, we identify that glutamine limitation in PDA cells suppresses de novo hexosamine synthesis but results in increased free GlcNAc abundance. GlcNAc salvage via N-acetylglucosamine kinase (NAGK) is engaged to feed UDP-GlcNAc pools.NAGKexpression is elevated in human PDA, andNAGKdeletion from PDA cells impairs tumor growth in mice. Together, these data identify an important role for NAGK-dependent hexosamine salvage in supporting PDA tumor growth.
pDeep3: Towards More Accurate Spectrum Prediction with Fast Few-Shot Learning
Authors: Tarn Ching , Zeng Wen-Feng 
Published: September 2020

AbstractSpectrum prediction using deep learning has attracted a lot of attention in recent years. Although existing deep learning methods have dramatically increased the pre-diction accuracy, there is still considerable space for improvement, which is presently limited by the difference of fragmentation types or instrument settings. In this work, we use the few-shot learning method to fit the data online to make up for the shortcoming. The method is evaluated using ten datasets, where the instruments includes Velos, QE, Lumos, and Sciex, with collision energies being differently set. Experimental results show that few-shot learning can achieve higher prediction accuracy with almost negligible computing resources. For example, on the dataset from a untrained instrument Sciex-6600, within about 10 seconds, the prediction accuracy is increased from 69.7% to 86.4%; on the CID (collision-induced dissociation) dataset, the prediction accuracy of the model trained by HCD (higher energy collision dissociation) spectra is increased from 48.0% to 83.9%. It is also shown that, the method is not critical to data quality and is sufficiently efficient to fill the accuracy gap. The source code of pDeep3 is available athttp://pfind.ict.ac.cn/software/pdeep3.
Sense of self impacts spatial navigation and hexadirectional coding in human entorhinal cortex
Authors: Moon Hyuk-June , Gauthier Baptiste , Park Hyeong-Dong , Faivre Nathan , Blanke Olaf 
Published: September 2020

AbstractGrid cells in entorhinal cortex (EC) encode an individual’s location in space and rely on environmental cues and self-motion cues derived from the individual’s body. Body-derived signals are also primary signals for the sense of self and self-identification with a body. However, it is currently unknown whether self-identification impacts grid cells and spatial navigation. Integrating the online manipulation of bodily signals, to modulate self-identification, into a spatial navigation task and with an fMRI measure to detect grid cell-like representation (GCLR) in humans, we report improved spatial navigation performance and decreased GCLR in EC when participants navigated with enhanced self-identification. These changes were further associated with increased activity in posterior parietal and retrosplenial cortex. Modulating self-identification by controlling online body-derived signals during spatial navigation, these data link the sense of self to spatial navigation and to entorhinal grid cell-like activity within a distributed cortical spatial navigation system.
PPARG in osteocytes is essential for sclerostin expression, bone mass, marrow adiposity and TZD-induced bone loss
Authors: Baroi Sudipta , Czernik Piotr J. , Chougule Amit , Griffin Patrick R. , Lecka-Czernik Beata 
Published: September 2020

AbstractPPARG role in regulation of osteocyte function is largely unknown. We report that PPARG is essential for sclerostin production, a recently approved target to treat osteoporosis. There is an excellent correlation in osteocytes betweenSost/sclerostin and PPARG at the transcript and protein levels, and increased bone mass in mice with osteocyte-specific deletion of PPARG (γOTKO) correlated with increased WNT signaling and bone forming activity of endosteal osteoblasts and decreased marrow fat. The 8 kb sequence upstream ofSostgene transcription start site possesses multiple PPARG binding elements (PPREs) with at least two of them binding PPARG with dynamics reflecting its activation and the levels ofSosttranscript and sclerostin protein expression. Older γOTKOfemale mice are largely protected from TZD-induced bone loss providing proof of concept that PPARG in osteocytes can be pharmacologically targeted. Our study opens the possibility to consider repurposing PPARG as a target for treatment of osteoporosis.
Circadian rhythms of early afterdepolarizations and ventricular arrhythmias in a cardiomyocyte model
Authors: Diekman Casey O. , Wei Ning 
Published: September 2020

AbstractSudden cardiac arrest is a malfunction of the heart’s electrical system, typically caused by ventricular arrhythmias, that can lead to sudden cardiac death (SCD) within minutes. Epidemiological studies have shown that SCD and ventricular arrhythmias are more likely to occur in the morning than in the evening, and laboratory studies indicate that these daily rhythms in adverse cardiovascular events are at least partially under the control of the endogenous circadian timekeeping system. However, the biophysical mechanisms linking molecular circadian clocks to cardiac arrhythmogenesis are not fully understood. Recent experiments have shown that L-type calcium channels exhibit circadian rhythms in both expression and function in guinea pig ventricular cardiomyocytes. We developed an electrophysiological model of these cells to simulate the effect of circadian variation in L-type calcium conductance. We found that there is a circadian pattern in the occurrence of early afterdepolarizations (EADs), which are abnormal depolarizations during the repolarization phase of a cardiac action potential that can trigger fatal ventricular arrhythmias. Specifically, the model produces EADs in the morning but not at other times of day. We show that the model exhibits a codimension-2 Takens-Bogdanov bifurcation that serves as an organizing center for different types of EAD dynamics. We also simulated a 2-D spatial version of this model across a circadian cycle. We found that there is a circadian pattern in the breakup of spiral waves, which represents ventricular fibrillation in cardiac tissue. Specifically, the model produces spiral wave breakup in the morning but not in the evening. Our study is the first to propose a link between circadian rhythms and EAD formation and suggests that the efficacy of drugs targeting EAD-mediated arrhythmias may depend on the time of day that they are administered.Significance StatementWhy are life-threatening cardiac arrhythmias more likely to occur in the morning than in the evening? The electrical properties of the heart exhibit daily rhythms due to molecular circadian clocks within cardiomyocytes. Our computational model of ventricular myocytes shows that clock-controlled expression of a voltage-gated calcium ion channel leads to early afterdepolarizations (EADs) at certain times of the day. EADs, in which the membrane potential of a cardiomyocyte depolarizes a second time before fully repolarizing, can trigger arrhythmias. To our knowledge, this is the first study linking the circadian clock to EAD formation. Our results suggest that the efficacy of anti-arrhythmic medications targeting this calcium ion channel may depend on the time of day the drug is taken.
Changing reward expectation transforms spatial encoding and retrieval in the hippocampus
Authors: Krishnan Seetha , Cherian Chery , Sheffield Mark. E. J. 
Published: September 2020

SummaryInternal states of reward expectation play a central role in influencing the strength of spatial memories. At the cellular level, spatial memories are represented through the firing dynamics of hippocampal place cells. However, it remains unclear how internal states of reward expectation influence place cell dynamics and exert their effects on spatial memories. Here we show that when reward expectation is altered, the same environment becomes encoded by a distinct ensemble of place cells at all locations. Further, when reward expectation is high versus low, place cells demonstrate enhanced reliability during navigation and greater stability across days at all locations within the environment. These findings reveal that when rewards are expected, neuromodulatory circuits that represent internal reward expectation support and strengthen the encoding and retrieval of spatial information by place cells at all locations that lead to reward. This enhanced spatial memory can be used to guide future decisions about which locations are most likely to lead to rewards that are crucial for survival.
A combined BSA-Seq and linkage mapping approach identifies genomic regions associated with Phytophthora root and crown rot resistance in squash
Authors: Vogel Gregory , LaPlant Kyle E. , Mazourek Michael , Gore Michael A. , Smart Christine D. 
Published: September 2020

AbstractPhytophthora root and crown rot, caused by the soilborne oomycete pathogenPhytophthora capsici, leads to severe yield losses in squash (Cucurbita pepo). To identify quantitative trait loci (QTL) involved in resistance to this disease, we crossed a partially resistant squash breeding line with a susceptible zucchini cultivar and evaluated over 13,000 F2seedlings in a greenhouse screen. Bulked segregant analysis with whole genome resequencing (BSA-Seq) resulted in the identification of five genomic regions – on chromosomes 4, 5, 8, 12, and 16 – featuring significant allele frequency differentiation between susceptible and resistant bulks in each of two independent replicates. In addition, we conducted linkage mapping using a population of 176 F3families derived from individually genotyped F2individuals. Variation in disease severity among these families was best explained by a four-QTL model, comprising the same loci identified via BSA-Seq on chromosomes 4, 5, and 8 as well as an additional locus on chromosome 19, for a combined total of six QTL identified between both methods. Loci, whether those identified by BSA-Seq or linkage mapping, were of small to moderate effect, collectively accounting for 28-35% and individually for 2-10% of the phenotypic variance explained. However, a multiple linear regression model using one marker in each BSA-Seq QTL could predict F2:3disease severity with only a slight drop in cross-validation accuracy compared to genomic prediction models using genome-wide markers. These results suggest that marker-assisted selection could be a suitable approach for improving Phytophthora crown and root rot resistance in squash.
Performance and efficiency of machine learning algorithms for analyzing rectangular biomedical data
Authors: Deng Fei , Huang Jibing , Yuan Xiaoling , Cheng Chao , Zhang Lanjing 
Published: September 2020

AbstractMost of the biomedical datasets, including those of ‘omics, population studies and surveys, are rectangular in shape and have few missing data. Recently, their sample sizes have grown significantly. Rigorous analyses on these large datasets demand considerably more efficient and more accurate algorithms. Machine learning (ML) algorithms have been used to classify outcomes in biomedical datasets, including random forests (RF), decision tree (DT), artificial neural networks (ANN) and support vector machine (SVM). However, their performance and efficiency in classifying multi-category outcomes in rectangular data are poorly understood. Therefore, we aimed to compare these metrics among the 4 ML algorithms. As an example, we created a large rectangular dataset using the female breast cancers in the Surveillance, Epidemiology, and End Results-18 (SEER-18) database which were diagnosed in 2004 and followed up until December 2016. The outcome was the 6-category cause of death, namely alive, non-breast cancer, breast cancer, cardiovascular disease, infection and other cause. We included 58 dichotomized features from ~53,000 patients. All analyses were performed using MatLab (version 2018a) and the 10-fold cross validation approach. The accuracy in classifying 6-category cause of death with DT, RF, ANN and SVM was 72.68%, 72.66%, 70.01% and 71.85%, respectively. Based on the information entropy and information gain of feature values, we optimized dimension reduction (i.e. reduce the number of features in models). We found 22 or more features were required to maintain the similar accuracy, while the running time decreased from 440s for 58 features to 90s for 22 features in RF, from 70s to 40s in ANN and from 440s to 80s in SVM. In summary, we here show that RF, DT, ANN and SVM had similar accuracy for classifying multi-category outcomes in this large rectangular dataset. Dimension reduction based on information gain will significantly increase model’s efficiency while maintaining classification accuracy.
Reducing antimicrobial usage in small-scale chicken farms in Vietnam: A three-year intervention study
Authors: Phu Doan Hoang , Van Cuong Nguyen , Truong Dinh Bao , Kiet Bach Tuan , Hien Vo Be , Viet Thu Ho Thi , Yen Lam Kim , Tuyet Minh Nguyen Thi , Padungtod Pawin , Setyawan Erry , Thwaites Guy , Rushton Jonathan , Carrique-Mas Juan 
Published: September 2020

AbstractIndiscriminate antimicrobial use (AMU) in animal production is a driver of antimicrobial resistance globally, with a need to define sustainable AMU-reducing interventions in small-scale farms typical of low- and middle-income countries. We conducted a before-and-after intervention study on a random sample of small-scale chicken farms in the Vietnamese Mekong Delta from 2016 to 2019. A baseline was established before providing farms (n=102) with veterinary advice on chicken health and husbandry, and antimicrobial replacement products. Thirty-five (34.2%) farms entered the intervention phase; the remainder no longer continued raising chickens. The intervention reduced AMU (−66%) (hazard ratio [HR]=0.34; p=0.002) (baseline 343.4 Animal Daily Doses per 1,000 chicken-days) and mortality (−40%) (HR=0.60; p=0.005) (weekly baseline 1.60 per 100). Chicken bodyweight increased by 100g (p=0.002) in intervention flocks. Our findings demonstrate that in the Vietnamese context, AMU can be substantially reduced in small-scale chicken farms without compromising flock health by providing veterinary advice.
Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors
Authors: Mavrommatis Lampros , Jeong Hyun-Woo , Kindler Urs , Gomez-Giro Gemma , Kienitz Marie-Cécile , Stehling Martin , Psathaki Olympia E. , Zeuschner Dagmar , Gabriele Bixel M. , Han Dong , Morosan-Puopolo Gabriela , Gerovska Daniela , Yang Ji Hun , Kim Jeong Beom , Araúzo-Bravo Marcos J. , Schwamborn Jens C. , Hahn Stephan A. , Adams Ralf H. , Schöler Hans R. , Vorgerd Matthias , Brand-Saberi Beate , Zaehres Holm 
Published: September 2020

AbstractIn vitro culture systems that structurally model human myogenesis and promote PAX7+myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis towards limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single cell comparison to human fetal and adult myogenic progenitors reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (CD44High/CD98+/MYOD1+) and dormant (PAX7High/FBN1High/SPRY1High) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.
Third-order aberration of soft X-ray optical systems with orthogonal and coplanar arrangement of the main planes of elements
Authors: Cao Yiqing , Shen Zhijuan , Xie Haihe 
Published: September 2020

A third-order aberration analytical analysis method of soft X-ray optical systems with orthogonal and coplanar arrangement of the main planes of elements is proposed. Firstly, the transfer equations of the aperture ray and the principle ray are derived; then, based on the third-order aberration theory with the aperture-ray coordinates on the reference exit wavefront of a plane-symmetric optical system, the aberration expressions contributed by the wave aberration and defocus of this kind of optical system are studied in detail. Finally, the derived aberration calculation expressions are applied to calculate the aberration of two design examples of such types of optical systems; the images are compared with ray-tracing results obtained using the Shadow software to validate the aberration expressions. The study shows that the accuracy of the aberration expressions is satisfactory. The analytical analysis method of aberration is helpful in the design and optimization of the soft X-ray optical systems with orthogonal and coplanar arrangement of the main planes of optical elements.
The impact of corporate governance on social and environmental engagement: what effect on firm performance in the food industry?
Authors: Gangi Francesco , D'Angelo Eugenio , Daniele Lucia Michela , Varrone Nicola 
Published: September 2020

PurposeThis paper aims to provide new evidence on firm-specific determinants and effects of corporate social and environmental responsibility (CSER) in the food industry.Design/methodology/approachThe current study is designed to empirically answer dual related research questions. First, we investigate the extent to which effective corporate governance (CG) mechanisms foster CSER. Second, we analyse the impact of CSER engagement on corporate financial performance (CFP). Consistent with the research design, to avoid sample selection bias, the authors employed Heckman two-step model (1979) to a worldwide sample of 324 food firms between 2011 and 2017.FindingsThe findings of the study reveal that effective board characteristics foster CSER engagement. Furthermore, CSER engagement is a positive predictor of improved profitability and also reduces the cost of debt (COD).Originality/valueThis article has elements of originality regarding the research questions, the context and the method. First, the authors demonstrate that CSER is a “missing link” between CG and CFP in the food industry. The authors’ contribution complements the debate on CSER and CFP through the stakeholder theory, the resource-based view and the innovation management perspective. They disentangle the effect of CG from the impact of social and environmental responsibility after correcting for endogeneity bias. The implications of the study contribute to a win-win scenario for companies investing in CG that result in higher CSER engagement, better profits and lower cost of capital.
Price Discovery and Transmission Mechanism between CDS and FX markets
Authors: Kim Hong Bae , Kang Sang Hoon 
Published: September 2020

This study investigated the relationship between the CDS (credit default swap) market with the FX spot (FX swap) market, including the period of recent global financial crisis.
A measure for market efficiency is the condition that the derivative markets dominate the asset market in price discovery. In our case, however, FX market should be leading the CDS market. We found FX (spot and Derivatives) market has co-integration relationship with CDS market. Looking at Gonzalo Granger (GG) and Hasbrouck's price discovery measure, we found the FX spot and derivatives market dominated CDS market in price discovery.
This study has also examined the direction of shock spillover and volatility transmission between Korean CDS spread and Foreign exchange spot (FX swap) markets using the VECM bivariate GARCH approach. Our evidence suggested the presence of bi-directional shock volatility and volatility transmission between the CDS market and FX spot market partially exist. However, volatility spillover effects from CDS market to FX Swap market are stronger than in the reverse direction during the global financial crisis, indicating that the CDS spread signaling sovereign risk play a more important role in influencing the volatility of FX derivatives market.
There are some particular features in FX market. The volatility and shock of CIP deviations reflecting arbitrage opportunities in FX swap market are influenced by those of CDS spread in tranquil period prior to Lehman failure. But after Lehman failure CDS played a crucial role in signaling credit risk in FX derivatives market. We found that higher liquidity and trading volume of market matters more in price discovery and information transmission.
Strategies for Improving V-KOSPI 200 Index
Authors: Kang Tae-Hun 
Published: September 2020

The study examines not only the methods for eliminating stale or abnormal prices but also strategies for enhancing liquidity in the KOSPI 200 index options market, for compensating the defects of V-KOSPI 200.
First, introducing market making scheme in the KOSPI 200 options market can be the direct solution to prevent temporary fluctuations and spikes of the index arising from abnormal orders and to alleviate unnatural low variability (level) of the index through decreasing the use of stale market prices (model prices).
Second, if weekly options underlying KOSPI 200 index are available for trading and investor interest in the weeklys are surged, Korea Exchange can enhance V-KOSPI 200 to include series of KOSPI 200 weekly options. The inclusion for at least 5~6 weekly options available for trading allow V-KOSPI 200 to be calculated with KOSPI 200 index option series that most precisely match the 30-day target time-frame for expected volatility that the Index is intended to represent.
Along with these strategies for enhancing liquidity in the KOSPI 200 index options market, the study suggests the methodology which can prevents temporary fluctuations and spikes of the index by substituting stale or abnormal prices for normal prices.