bluuebunny/crossref_metadata_2025_split huggingface dataset:
The differentiation of pluripotent stem cells towards transplantable endothelial progenitor cells
Authors: Qin Kezhou , Yang Jun 
Published: February 2021

AbstractEndothelial progenitor cells (EPCs) and endothelial cells (ECs) have been applied in the clinic to treat pulmonary arterial hypertension (PAH), a disease characterized by disordered pulmonary vasculature. However, the lack of sufficient transplantable cells before the deterioration of disease condition is a current limitation to apply cell therapy in patients. It is necessary to differentiate pluripotent stem cells (PSCs) into EPCs and identify their characteristics. Comparing previously reported methods of human PSCs-derived ECs, we optimized a highly efficient differentiation protocol to obtain cells that match the phenotype of isolated EPCs from healthy donors. The protocol is compatible with chemically defined medium (CDM), it could produce a large number of clinically applicable cells with low cost. Moreover, we also found PSCs-derived EPCs express CD133, have some characteristics of mesenchymal stem cells and are capable of homing to repair blood vessels in zebrafish xenograft assays. In addition, we further revealed that IPAH PSCs-derived EPCs have higher expression of proliferation-related genes and lower expression of immune-related genes than normal EPCs and PSCs-derived EPCs through microarray analysis. In conclusion, we optimized a highly efficient differentiation protocol to obtain PSCs-derived EPCs with the phenotypic and molecular characteristics of EPCs from healthy donors which distinguished them from EPCs from PAH.
Structure of human Nav1.5 reveals the fast inactivation-related segments as a mutational hotspot for the Long QT Syndrome
Authors: Li Zhangqiang , Jin Xueqin , Wu Tong , Zhao Xin , Wang Weipeng , Lei Jianlin , Pan Xiaojing , Yan Nieng 
Published: February 2021

AbstractNav1.5 is the primary voltage-gated Na+(Nav) channel in the heart. Mutations of Nav1.5 are associated with various cardiac disorders exemplified by the type 3 long QT syndrome (LQT3) and Brugada syndrome (BrS). E1784K is a common mutation that has been found in both LQT3 and BrS patients. Here we present the cryo-EM structure of the human Nav1.5-E1784K variant at an overall resolution of 3.3 Å. Structural mapping of 91 and 178 point mutations that are respectively associated with LQT3 and BrS reveals a unique distribution pattern for LQT3 mutations. Whereas the BrS mutations spread evenly on the structure, LQT3 mutations are mainly clustered to the segments in repeats III and IV that are involved in gating, voltage-sensing, and particularly inactivation. A mutational hotspot involving the fast inactivation segments is identified and can be mechanistically interpreted by our “door wedge” model for fast inactivation. The structural analysis presented here, with a focus on the impact of disease mutations on inactivation and late sodium current, establishes a structure-function relationship for the mechanistic understanding of Nav1.5 channelopathies.
Subgenomic RNAs as molecular indicators of asymptomatic SARS-CoV-2 infection
Authors: Wong Chee Hong , Ngan Chew Yee , Goldfeder Rachel L. , Idol Jennifer , Kuhlberg Chris , Maurya Rahul , Kelly Kevin , Omerza Gregory , Renzette Nicholas , De Abreu Francine , Li Lei , Browne Frederick A. , Liu Edison T. , Wei Chia-Lin 
Published: February 2021

SummaryIn coronaviridae such as SARS-CoV-2, subgenomic RNAs (sgRNA) are replicative intermediates, therefore, their abundance and structures could infer viral replication activity and severity of host infection. Here, we systematically characterized the sgRNA expression and their structural variation in 81 clinical specimens collected from symptomatic and asymptomatic individuals with a goal of assessing viral genomic signatures of disease severity. We demonstrated the highly coordinated and consistent expression of sgRNAs from individuals with robust infections that results in symptoms, and found their expression is significantly repressed in the asymptomatic infections, indicating that the ratio of sgRNAs to genomic RNA (sgRNA/gRNA) is highly correlated with the severity of the disease. Using long read sequencing technologies to characterize full-length sgRNA structures, we also observed widespread deletions in viral RNAs, and identified unique sets of deletions preferentially found primarily in symptomatic individuals, with many likely to confer changes in SARS-CoV-2 virulence and host responses. Furthermore, based on the sgRNA structures, the frequently occurred structural variants in SARS-CoV-2 genomes serves as a mechanism to further induce SARS-CoV-2 proteome complexity. Taken together, our results show that differential sgRNA expression and structural mutational burden both appear to be correlated with the clinical severity of SARS-CoV-2 infection. Longitudinally monitoring sgRNA expression and structural diversity could further guide treatment responses, testing strategies, and vaccine development.
A behavioral syndrome linking boldness and flexibility facilitates invasion success in sticklebacks
Authors: Bensky Miles K. , Bell Alison M. 
Published: February 2021

ABSTRACTFor a species to expand its range, it needs to be good at dispersing and also capable of exploiting resources and adapting to different environments. Therefore, behavioral and cognitive traits could play key roles in facilitating invasion success. Here, we show that dispersing sticklebacks are bold, while sticklebacks that have recently established in a new region are flexible. Moreover, boldness and flexibility are negatively correlated with one another at the individual, family and population levels. Multiple lines of evidence suggest that the divergence in boldness and flexibility is likely to be evolutionary in origin. If boldness is favored in invaders during the initial dispersal stage, while flexibility is favored in recent immigrants during the establishment stage, then the link between boldness and flexibility could generate positive correlations between successes during both dispersal and establishment, and therefore play a key role in facilitating colonization success in sticklebacks and other organisms.
Discovery of fungal-specific targets and inhibitors using chemical phenotyping of pathogenic spore germination
Authors: Ortiz Sébastien C. , Huang Mingwei , Hull Christina M. 
Published: February 2021

AbstractThere is a critical need for new antifungal drugs; however, the lack of available fungal-specific targets is a major hurdle in the development of antifungal therapeutics. Spore germination is a differentiation process absent in humans that could harbor uncharacterized fungal-specific targets. To capitalize on this possibility, we developed novel phenotypic assays to identify and characterize inhibitors of spore germination of the human fungal pathogenCryptococcus. Using these assays, we carried out a high throughput screen of ~75,000 drug-like small molecules and identified and characterized 191 novel inhibitors of spore germination, many of which also inhibited yeast replication and demonstrated low cytotoxicity against mammalian cells. Using an automated, microscopy-based, quantitative germination assay (QGA), we discovered that germinating spore populations can exhibit unique phenotypes in response to chemical inhibitors. Through the characterization of these spore population dynamics in the presence of the newly identified inhibitors, we classified 6 distinct phenotypes based on differences in germination synchronicity, germination rates, and overall population behavior. Similar chemical phenotypes were induced by inhibitors that targeted the same cellular function or had shared substructures. Leveraging these features, we used QGAs to identify outliers among compounds that fell into similar structural groups and thus refined relevant structural moieties, facilitating target identification. This approach led to the identification of complex II of the electron transport chain as the putative target of a promising structural cluster of germination inhibitory compounds. These inhibitors showed high potency againstCryptococcusspore germination, while maintaining low cytotoxicity against mammalian cells, making them prime candidates for development into novel antifungal therapeutics.
Ex vivodelivery of regulatory T cells for control of alloimmune priming in the donor lung
Authors: Miyamoto Ei , Takahagi Akihiro , Ohsumi Akihiro , Martinu Tereza , Hwang David , Boonstra Kristen M. , Joe Betty , Umana Juan Mauricio , Bei Ke F. , Vosoughi Daniel , Liu Mingyao , Cypel Marcelo , Keshavjee Shaf , Juvet Stephen C. 
Published: February 2021

AbstractSurvival after lung transplantation (LTx) is hampered by uncontrolled inflammation and alloimmunity. Regulatory T cells (Tregs) are being studied for post-implantation cell therapy in solid organ transplantation. Whether these systemically administered Tregs can function at the appropriate location and time is an important concern. We hypothesized thatin vitroexpanded, recipient-derived Tregs can be delivered to donor lungs prior to LTx viaex vivolung perfusion (EVLP), maintaining their immunomodulatory ability.In a rat model, Wistar Kyoto (WKy) CD4+CD25highTregs were expandedin vitroprior to EVLP. Expanded Tregs were administered to Fisher 344 (F344) donor lungs during EVLP; left lungs were transplanted into WKy recipients. Treg localization and function post-transplant were assessed. In a proof-of-concept experiment, cryopreserved expanded human CD4+CD25+CD127lowTregs were thawed and injected into discarded human lungs during EVLP. Rat Tregs entered the lung parenchyma and retained suppressive function. Expanded Tregs had no adverse effect on donor lung physiology during EVLP; lung water as measured by wet- to-dry weight ratio was reduced by Treg therapy. The administered cells remained in the graft at 3 days post-transplant where they reduced activation of intragraft effector CD4+T cells; these effects were diminished by day 7. Human Tregs entered the lung parenchyma during EVLP where they expressed key immunoregulatory molecules (CTLA4+, 4-1BB+, CD39+, and CD15s+). Pre-transplant Treg administration can inhibit alloimmunity within the lung allograft at early time points post- transplant. Our organ-directed approach has potential for clinical translation.
Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data
Authors: Hatti Kaushik S , McCoy Airlie J , Read Randy J 
Published: February 2021

AbstractSAD phasing can be challenging when the signal-to-noise ratio is low. In such cases, having an accurate estimate of substructure content can determine whether or not the substructure of anomalous scatterer positions can successfully be determined. We propose a likelihood-based target function to accurately estimate the strength of the anomalous scattering contribution directly from measured intensities, determining a complex correlation parameter relating the Bijvoet mates as a function of resolution. This gives a novel measure of intrinsic anomalous signal. The SAD likelihood target function also accounts for correlated errors in the measurement of intensities from Bijvoet mates, which can arise from the effects of radiation damage. When the anomalous signal is assumed to come primarily from a substructure comprised of one anomalous scatterer with a known value of f” and when the protein composition of the crystal is estimated correctly, the refined complex correlation parameters can be interpreted in terms of the atomic content of the primary anomalous scatterer, before the substructure is known. The maximum likelihood estimation of substructure content was tested on a curated database of 357 SAD cases with useful anomalous signal. The prior estimates of substructure content are highly correlated to the content determined by phasing calculations, with a correlation coefficient (on a log-log basis) of 0.72.SynopsisAn intensity-based likelihood method is provided to estimate scattering from an anomalous substructure considering the effect of measurement errors in Bijvoet pairs and correlations between those errors.
Wave propagation and focusing of soft X-rays by spherical bent microchannel plates
Authors: Mazuritskiy M. I. , Lerer A. M. , Marcelli A. , Dabagov S. B. , Coreno M. , D'Elia A. , Rezvani S. J. 
Published: February 2021

Synchrotron radiation sources have been used to study the focusing properties and angular distribution of X-ray radiation at the exit of spherically bent microchannel plates (MCPs). In this contribution it is shown how soft X-ray radiation at energies up to 1.5 keV can be focused by spherically bent MCPs with curvature radii R of 30 mm and 50 mm. For these devices, a focus spot is detectable at a distance between the detector and the MCP of less than R/2, with a maximum focusing efficiency up to 23% of the flux illuminating the MCP. The soft X-ray radiation collected at the exit of microchannels of spherically bent MCPs are analyzed in the framework of a wave approximation. A theoretical model for the wave propagation of radiation through MCPs has been successfully introduced to explain the experimental results. Experimental data and simulations of propagating radiation represent a clear confirmation of the wave channeling phenomenon for the radiation in spherically bent MCPs.
Upgrade of the SPECIES beamline at the MAX IV Laboratory
Authors: Kokkonen Esko , Lopes da Silva Felipe , Mikkelã Mikko-Heikki , Johansson Niclas , Huang Shih-Wen , Lee Jenn-Min , Andersson Margit , Bartalesi Antonio , Reinecke Benjamin N. , Handrup Karsten , Tarawneh Hamed , Sankari Rami , Knudsen Jan , Schnadt Joachim , Såthe Conny , Urpelainen Samuli 
Published: February 2021

The SPECIES beamline has been transferred to the new 1.5 GeV storage ring at the MAX IV Laboratory. Several improvements have been made to the beamline and its endstations during the transfer. Together the Ambient Pressure X-ray Photoelectron Spectroscopy and Resonant Inelastic X-ray Scattering endstations are capable of conducting photoelectron spectroscopy in elevated pressure regimes with enhanced time-resolution and flux and X-ray scattering experiments with improved resolution and flux. Both endstations offer a unique capability for experiments at low photon energies in the vacuum ultraviolet and soft X-ray range. In this paper, the upgrades on the endstations and current performance of the beamline are reported.
Experimental and numerical simulation of the piston engine fueled with alternative fuel blends: CFD approach
Authors: Gaikwad Pradeep Uttam , Gnanamani Senthil , Subramani Nithya 
Published: February 2021

Purpose
The purpose of this paper is to find the pressure and the knocking phenomena. To get the pressure values, the butterworth bandpass filter was used and the potential of knocking was found by using peak-to-peak pressure values and also the species concentration. Cooled exhaust gas recirculation was the method used to minimize the knocking occurrence in the engine. Moreover, the effect of premixed methanol and start of engine (SOI) on knocking were also determined.

Design/methodology/approach
This paper deals with the compression ignition engine to investigate the unfavorable knocking behavior. The tests were carried out with the 3D model of engine fueled with waste cooking oil blended with TiO2. A number of tests were taken to find the pressure variation and the species concentration at eight different locations in the computational model.

Findings
In doing the tests, the positive intended outcome was achieved. From results, it is clear that the SOI and premixed methanol mitigated the knocking process.

Originality/value
The species concentration and pressure in the form of filtered signal were proved to be the ideal methods for evaluating the knocking event in the engine.
Effect of storage temperature on the crispness, colour and bioactive compounds of an orange snack obtained by freeze-drying
Authors: Silva-Espinoza Marilú Andrea , Camacho María del Mar , Martínez-Navarrete Nuria 
Published: February 2021

PurposeA healthy and easy-to-use orange snack obtained from the freeze-dried orange pulp puree is proposed. Once the commercial packaging of the snack has been opened, the effect of conventional home storage temperature on its physicochemical properties and on the content of bioactive compounds has been studied. This research aims to recommend the consumer, and therefore the manufacturer, the best conditions for home storage of this product, keeping its nutritional quality and antioxidant capacity, as well as maintaining its colour and crispness.Design/methodology/approachThe water content, water activity, hygroscopicity, crispness, colour, vitamin C, β-carotene, total phenolic compounds and antioxidant activity were characterised both when the orange snack was newly obtained and after one, two and six months of storage inside zipper bags, at 4 and 20 ºC.FindingsThe results indicated that, in these conditions, the orange snack increased its water content, causing a loss in both its porosity and its characteristic crispness. Nevertheless, the bioactive compounds remained stable throughout the storage period, with the exception of β-carotene, the content of which decreased markedly when the orange snack was stored at 20 ºC.Originality/valueFew studies have evaluated the stability of food products during home storage. The findings showed that the maximum storage time to ensure a proper texture of the orange snack studied is between two and six months, both at 4 and 20 ºC. However, from the point of view of the conservation of both vitamin C and, especially, of β-carotene, it is recommended that this product be stored in refrigeration.
Identification of cause and effect relationships among barriers of Industry 4.0 using decision-making trial and evaluation laboratory method
Authors: Nimawat Dheeraj , Gidwani B.D. 
Published: February 2021

PurposeIndustry 4.0 is regarded as a modern industrial phase wherein convergence between horizontal and vertical production systems, along with their interactions, would enable industries to obtain excellent industrial efficiency. This research thus explores the barriers relevant to Industry 4.0 and their cause and effect relations using the decision-making trial and evaluation laboratory (DEMATEL) technique, and this will assist in the implementation of Industry 4.0 in manufacturing industries.Design/methodology/approachA comprehensive literature review is carried out to outline the barriers for the Industry 4.0 implementation. The investigative techniques used in this research were conducted utilizing a questionnaire as an instrument for collecting data. The data collected were analysed using the method DEMATEL.FindingsThe findings indicate that key barriers to implementing Industry 4.0 include their cause and effect relationships. Reported “implementation costs” have been a critical barrier for Industry 4.0 implementation. Prioritization of barriers and their cause and effect relationships was achieved so that decision-makers could concentrate on overcoming such barriers for Industry 4.0 implementation.Practical implicationsThe research is intended to assist executives in recognizing the barriers to Industry 4.0 implementation in their manufacturing industries. Furthermore, the strong functional and empirical importance of emerging and digital manufacturing technologies ensures that understanding the necessary barriers to implementation is important.Originality/valueThis is one of the first few empirical studies in the field of Indian manufacturing industries that uses the DEMATEL method framework as a foundation for recognizing cause-effect interactions among the barriers that affect Industry 4.0.
Impact of earnings management on agency costs: evidence from MILA markets
Authors: Muñoz Mendoza Jorge Andrés , Veloso Ramos Carmen Lissette , Sepúlveda Yelpo Sandra María , Delgado Fuentealba Carlos Leandro , Fuentes-Solís Rodrigo Alberto 
Published: February 2021

PurposeThe purpose of this article is to analyze the effects of accruals-based earnings management (AEM), International Financial Reporting Standard (IFRS) adoption and stock market integration for firms that belong to Latin-American Integrated Market (MILA).Design/methodology/approachThe GMM estimator was used according to Arellano and Bover (1995) for panel data on a sample of 478 non-financial companies between 2000 and 2016. Multilevel mixed models was used for the robustness analysis.FindingsAEM practices significantly and dynamically reduce agency costs. This result suggests companies use positive discretionary accruals to hide true agency costs and avoid shareholders monitoring, while negative discretionary accruals are ways to expropriate wealth and increase agency costs. This result implies that firms use AEM as a predetermined strategy to weaken corporate governance. The IFRS adoption and MILA implementation reduced agency costs. However, only IFRS adoption had the capability to mitigate the effects of AEM on agency costs.Originality/valueThese results reveal AEM constitutes a practice that managers use to weaken firms’ corporate governance and expropriate wealth from shareholders. These practices have effects at short-run and long-run. However, the IFRS adoption and market integration represented by MILA are mitigating factors for agency costs. These results have relevant implications for firms’ corporate governance because they guide investors and shareholders to strengthen corporate control and monitoring on business decision-making. These results also are relevant to policymakers because they orient the financial policies design to strengthen the benefits of IFRS and MILA.
The impact of board composition on the dividend policy of US firms
Authors: Thompson Ephraim Kwashie , Adasi Manu Sylvester 
Published: February 2021

PurposeThis paper aims to examine whether the characteristics of boards are more important in determining dividend policy than management characteristics. The authors show that as the final declarers of dividend policy is a firm’s board, the composition of a firm’s board significantly subsumes the effect of management characteristics that may also influence dividend policy.Design/methodology/approachUsing the dividend declaration dummy variable, the authors run a fixed effect logistic regression of the dividend indicator on board characteristics, and managerial characteristics with firm level controls, year effects and industry effects while clustering standard errors at the firm level. For dividend yield variable which is censored at zero, they use a fixed effect Tobit regression.FindingsThe results of the study show that board characteristics such as average age, female presence and size have a strong positive significant effect, whereas board independent chair and voting right of directors have a negative significant effect on the likelihood of dividend declaration. For dividend yields, the results suggest that the presence of directors with financial expertise and the board size are the main influencers of dividend policy. Managerial characteristics are subsumed by director characteristics for determining dividend policy. The results overall support the evidence on the monitoring role of boards on management.Originality/valueThe originality and value of this study lies in the approach of including a comprehensive number of board characteristics unlike previous studies which makes the study of the influence of board composition on dividends more encompassing.