bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual function of perivascular fibroblasts in vascular stabilization in zebrafish
Authors: Rajan Arsheen M. , Ma Roger C. , Kocha Katrinka M. , Zhang Dan J. , Huang Peng 
Published: April 2020

ABSTRACTBlood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types to vascular stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibroblasts as a novel population of blood vessel associated cells. In contrast to pericytes, perivascular fibroblasts emerge early during development, express the extracellular matrix (ECM) genescol1a2andcol5a1, and display distinct morphology and distribution. Time-lapse imaging reveals that perivascular fibroblasts serve as pericyte precursors. Genetic ablation of perivascular fibroblasts results in dysmorphic blood vessels with variable diameters. Strikingly,col5a1mutants show spontaneous hemorrhage, and the penetrance of the phenotype is strongly enhanced by the additional loss ofcol1a2. Together, our work reveals dual roles of perivascular fibroblasts in vascular stabilization where they establish the ECM around nascent vessels and function as pericyte progenitors.AUTHOR SUMMARYBlood vessels are essential to sustain life in humans. Defects in blood vessels can lead to serious diseases, such as hemorrhage, tissue ischemia, and stroke. However, how blood vessel stability is maintained by surrounding support cells is still poorly understood. Using the zebrafish model, we identify a new population of blood vessel associated cells termed perivascular fibroblasts, which originate from the sclerotome, an embryonic structure that is previously known to generate the skeleton of the animal. Perivascular fibroblasts are distinct from pericytes, a known population of blood vessel support cells. They become associated with blood vessels much earlier than pericytes and express several collagen genes, encoding main components of the extracellular matrix. Loss of perivascular fibroblasts or mutations in collagen genes result in fragile blood vessels prone to damage. Using cell tracing in live animals, we find that a subset of perivascular fibroblasts can differentiate into pericytes. Together, our work shows that perivascular fibroblasts play two important roles in maintaining blood vessel integrity. Perivascular fibroblasts secrete collagens to stabilize newly formed blood vessels and a sub-population of these cells also functions as precursors to generate pericytes to provide additional vascular support.
Role of 1’-Ribose Cyano Substitution for Remdesivir to Effectively Inhibit Nucleotide Addition and Proofreading in SARS-CoV-2 Viral RNA Replication
Authors: Zhang Lu , Zhang Dong , Wang Xiaowei , Yuan Congmin , Li Yongfang , Jia Xilin , Gao Xin , Yen Hui-Ling , Cheung Peter Pak-Hang , Huang Xuhui 
Published: April 2020

ABSTRACTCOVID-19 has recently caused a global health crisis and an effective interventional therapy is urgently needed. SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is a promising but challenging drug target due to its intrinsic proofreading exoribonuclease (ExoN). Remdesivir targeting SARS-CoV-2 RdRp exerts high drug efficacyin vitroandin vivo. However, its underlying inhibitory mechanisms remain elusive. Here, we performed all-atom molecular dynamics simulations with an accumulated simulation time of 24 microseconds to elucidate the molecular mechanisms underlying the inhibitory effects of Remdesivir. We found that Remdesivir’s 1’-cyano group of possesses the dual role of inhibiting nucleotide addition and proofreading. The presence of its polar 1’-cyano group at an upstream site in RdRp causes instability and hampers RdRp translocation. This leads to a delayed chain termination of RNA extension, which may also subsequently reduce the likelihood for Remdesivir to be cleaved by ExoN acting on the 3’-terminal nucleotide. In addition, our simulations suggest that Remdesivir’s 1’-cyano group can also disrupt the cleavage active site of ExoN via steric interactions, leading to a further reduced cleavage efficiency. Our work provides plausible molecular mechanisms on how Remdesivir inhibits viral RNA replication and may guide rational design for new treatments of COVID-19 targeting viral replication.
Trackosome: a computational toolbox to study the spatiotemporal dynamics of centrosomes, nuclear envelope and cellular membrane
Authors: Castro Domingos , Nunes Vanessa , Lima Joana T. , Ferreira Jorge G. , Aguiar Paulo 
Published: April 2020

AbstractDuring the initial stages of mitosis, multiple mechanisms drive centrosome separation and positioning. How they are functionally coordinated to promote centrosome migration to opposite sides of the nucleus remains unclear. Imaging analysis software has been used to quantitatively study centrosome dynamics at this stage. However, available tracking tools are generic and not fine-tuned for the constrains and motion dynamics of centrosome pairs. Such generality limits the tracking performance and may require exhaustive optimization of parameters. Here, we present Trackosome, a freely available open-source computational tool to track the centrosomes and reconstruct the nuclear and cellular membranes, based on volumetric live-imaging data. The toolbox runs in MATLAB and provides a graphical user interface for easy and efficient access to the tracking and analysis algorithms. It outputs key metrics describing the spatiotemporal relations between centrosomes, nucleus and cellular membrane. Trackosome can also be used to measure the dynamic fluctuations of the nuclear envelope. A fine description of these fluctuations is important because they are correlated with the mechanical forces exerted on the nucleus by its adjacent cytoskeletal structures. Unlike previous algorithms based on circular/elliptical approximations of the nucleus, Trackosome measures membrane movement in a model-free condition, making it viable for irregularly shaped nuclei. Using Trackosome, we demonstrate significant correlations between the movements of the two centrosomes, and identify specific modes of oscillation of the nuclear envelope. Overall, Trackosome is a powerful tool to help unravel new elements in the spatiotemporal dynamics of subcellular structures.
Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice
Authors: Pruijssers Andrea J. , George Amelia S. , Schäfer Alexandra , Leist Sarah R. , Gralinksi Lisa E. , Dinnon Kenneth H. , Yount Boyd L. , Agostini Maria L. , Stevens Laura J. , Chappell James D. , Lu Xiaotao , Hughes Tia M. , Gully Kendra , Martinez David R. , Brown Ariane J. , Graham Rachel L. , Perry Jason K. , Du Pont Venice , Pitts Jared , Ma Bin , Babusis Darius , Murakami Eisuke , Feng Joy Y. , Bilello John P. , Porter Danielle P. , Cihlar Tomas , Baric Ralph S. , Denison Mark R. , Sheahan Timothy P. 
Published: April 2020

SUMMARYSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50= 0.01 μM). Weaker activity was observed in Vero E6 cells (EC50= 1.65 μM) due to their low capacity to metabolize RDV. To rapidly evaluatein vivoefficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminished lung viral load and improved pulmonary function as compared to vehicle treated animals. These data provide evidence that RDV is potently active against SARS-CoV-2in vitroandin vivo, supporting its further clinical testing for treatment of COVID-19.
Screening of additives for droplet qRT-PCR thermocycling enables single influenza A virus genome quantification
Authors: Loveday Emma Kate , Zath Geoffrey K. , Bikos Dimitri A. , Jay Zackary J. , Chang Connie B. 
Published: April 2020

AbstractThe miniaturization of real time quantitative polymerase chain reaction (qPCR) using drop-based microfluidics, or droplet qPCR, allows for quantification of single nucleic acids. The nucleic acids are compartmentalized into aqueous microdroplets, picoliters in volume, separated by an immiscible oil, and stabilized by a surfactant. In droplet qPCR, accurate data can only be obtained if the drops remain stable to coalescence upon thermocycling and drop contents do not diffuse to neighboring drops. In this work, we present a droplet qRT-PCR assay for quantifying influenza A virus (IAV) following systematic testing of different PCR additives, resulting in the optimal combination of Tween-20 / BSA / betaine to maintain drop stability and limit dye diffusion. We use a standard qPCR machine to generate real time amplification curves of hundreds of thousands of drops and correlate this data with constructed amplification curves obtained from hundreds of drops sampled at various cycle numbers and imaged using epifluorescence microscopy. To demonstrate the utility of our method, we tested a range ofin vitrotranscribed M gene and IAV viral supernatant from infected cells. We directly amplified IAV genomes from infected supernatant without an RNA extraction step. Our droplet qPCR assay enables detection of IAV down to 0.274 cpd, or a single viral genome per drop, establishing the high sensitivity and precision of our method.
The spectacle of research assessment systems: insights from New Zealand and the United Kingdom
Authors: Chatterjee Bikram , Cordery Carolyn J. , De Loo Ivo , Letiche Hugo 
Published: April 2020

PurposeIn this paper, we concentrate on the use of research assessment (RA) systems in universities in New Zealand (NZ) and the United Kingdom (UK). Primarily we focus on PBRF and REF, and explore differences between these systems on individual and systemic levels. We ask, these days, in what way(s) the systemic differences between PBRF and REF actually make a difference on how the two RA systems are experienced by academic staff.Design/methodology/approachThis research is exploratory and draws on 19 interviews in which accounting researchers from both countries offer reflections on their careers and how RA (systems) have influenced these careers. The stories they tell are classified by regarding RA in universities as a manifestation of the spectacle society, following Debord (1992) and Flyverbom and Reinecke (2017).FindingsBoth UK and New Zealand academics concur that their research activities and views on research are very much shaped by journal rankings and citations. Among UK academics, there seems to be a greater critical attitude towards the benefits and drawbacks of REF, which may be related to the history of REF in their country. Relatively speaking, in New Zealand, individualism seems to have grown after the introduction of the PBRF, with little active pushback against the system. Cultural aspects may partially explain this outcome. Academics in both countries lament the lack of focus on practitioner issues that the increased significance of RA seems to have evoked.Research limitations/implicationsThis research is context-specific and may have limited applicability to other situations, academics or countries.Practical implicationsRA and RA systems seem to be here to stay. However, as academics we can, and ought to, take responsibility to try to ensure that these systems reflect the future of accounting (research) we wish to create. It is certainly not mainly or solely up to upper management officials to set this in motion, as has occasionally been claimed in previous literature. Some of the academics who participated in this research actively sought to bring about a different future.Originality/valueThis research provides a unique contextual analysis of accounting academics' perspectives and reactions to RA and RA systems and the impact these have had on their careers across two countries. In addition, the paper offers valuable critical reflections on the application of Debord's (1992) notion of the spectacle society in future accounting studies. We find more mixed and nuanced views on RA in academia than many previous studies have shown.
Research supervision in distance learning: issues and challenges
Authors: Zaheer Muhammad , Munir Saba 
Published: April 2020

PurposeThe purpose of this study is to explore and highlight the issues and challenges teachers face while supervising thesis and projects in distance/online learning mode.Design/methodology/approachThis is a cross-sectional qualitative study. Grounded theory approach using Gioia methodology has been applied. Semi-structured interviews of 16 research supervisors have been conducted to explore the issues and challenges faced by the supervisors in guiding research students. Purposive sampling is used to select the subjects for data collection.FindingsResults of the study reveal that the time constraints, official restrictions, irregular contacts and technology are the main issues faced by supervisors. Whereas student–supervisor interaction, diversity, perceptions, virtual communities and academic collaboration are the biggest challenges for the supervisors in distance learning. Lastly, it is found that students' attitude and supervisors' mindset are the key success factors in distance research supervision.Practical implicationsFindings of this paper will help institutions particularly in Asia, to strategically review their research programs to make these programs more effective. Effectiveness will encompass two things, timely completion and novel research. If these two things are addressed efficiently, comparison of distance learning with conventional learning will be more favorable for distance learning.Originality/valueThis study will be helpful for the top management of distance/online learning institutes to better equip their teachers and students to complete their research endeavors accordingly. This is an empirical research based on primary data collected from the research supervisors currently supervising thesis/projects at Virtual University of Pakistan.
The effect of data strategy on competitive advantage
Authors: Medeiros Mauricius Munhoz de , Maçada Antonio Carlos Gastaud , Freitas Junior José Carlos da Silva 
Published: April 2020

Purpose
In the age of analytical competition, business models and gaining competitive advantage (CA) are directly related to organizations’ data strategy. Incorporating data strategy enables the organization to unlock the potential value of big data analytics. Therefore, this study aims to analyze how data strategy affects the achievement of CA.

Design/methodology/approach
Through survey research, data were collected from 103 respondents. Model testing and evaluation, partial least squares structural equation modeling and analysis of mediating effects were performed.

Findings
The supported hypotheses confirm the direct effects between the defensive and offensive positioning of the data strategy on CA, as well as the mediating effect of the offensive data strategy (ODS).

Originality/value
This study is groundbreaking in terms of empirically analyzing how defensive data strategy (DDS) or ODS affects CA. In conclusion, to extract value from their data, organizations need to establish their data strategy based on their strategic positioning, the potential of their resources and their analytical capabilities.

Research implications
The defensive and offensive positioning of the data strategy are closely related to each other and both, in isolation, directly and positively, impact CA. It is also noted that the role of defensive positioning is to strengthen the offensive positioning of the data strategy, which in turn, plays a central role in achieving CA.

Practical implications
The results can assist managers in effectively incorporating analytical resources and capabilities, as well as helping them understand the dynamics and advantages of data strategy, so they can drive strategic objectives according to the organization’s positioning.

Originality/value
This study is groundbreaking in terms of empirically analyzing how DDS or ODS affects CA. In conclusion, to extract value from their data, organizations need to establish their data strategy based on their strategic positioning, the potential of their resources and their analytical capabilities.
Multiple rational management and governance in agriculture cooperatives
Authors: Teixeira Maísa Gomide , Caleman Silvia Morales de Queiroz , Américo Jean Carlos da Silva 
Published: April 2020

PurposeThis study aims to analyze how multirational management relates to cooperatives’ corporate governance.Design/methodology/approachA typology of agricultural cooperatives’ potential for multirational management in relation to corporate governance is proposed. Coordinates based on data from assembly participation and separation of ownership and control are used to map cooperatives among these typologies. Four case studies representing each typology were conducted, allowing analysis of propositions.FindingsBy mapping the cooperatives from Mato Grosso do Sul, a reduced potential for multirational management is noted. By analyzing the four case studies, coded as Coop 1, 3, 13 and 16, this study found convergence withP1,P2andP3. “Coop 1” shows signs of adopting exploitation practice. In “Coop 3,” evidence points to avoidance practice and, analyses of “Coop 13” indicates adoption of tolerance practice. In Coop 16, however,P4could not be confirmed. Instead of polarizing practices, there is evidence of avoidance practice. Therefore, a positive relation between corporate governance and multirational management can partially be observed.Originality/valueThere are no records of a paper that has explored the relation of governance and multirational management. Therefore, this research broadens the understanding of how corporate governance can function in the context of cooperative organizations. As well, insight is given on how different mechanisms of corporate governance can influence organizations to adopt explicit or implicit and monorational or multirational methods of dealing with multiple rationalities.
Role of discretionary earning management in corporate governance-value and corporate governance-risk relationships
Authors: Asghar Affaf , Sajjad Seemab , Shahzad Aamer , Matemilola Bolaji Tunde 
Published: April 2020

PurposeCorporate governance (CG) is an ongoing interesting topic getting the attention of market participant, business regulators and researchers in today’s business environment. The purpose of this study is to analyze the moderating role of earnings management on CG-value and CG-risk relationship in the emerging economy of Pakistan.Design/methodology/approachA panel data analysis is used in this study. A panel data of 71 non-financial listed companies of Pakistan for the 2008-2017 period is considered for this study. Secondary data is collected from the annual reports of non-financial firms listed on PSX. Seven econometric equations are developed to test the research hypothesis.FindingsThe results reveal that CG significantly enhances the firm value and performance measures. Moreover, CG mitigates the practices of earning management and eliminates the risk that develops opportunistic behavior among managers to commit frauds.Practical implicationsThe results of this study suggest that the board of directors (BODs) should intensify their governance role and ensure that the executives perform their duties to maximize the wealth of the shareholders and not engage in any misrepresentation of accounts that may lower the company position and decrease the firm value. Moreover, the managers should be informed about their accountability and acknowledged that at the end of the year, they would be audited by an expert’s auditors for their responsibilities. Concerning regulatory bodies, regulatory authorities should ensure that there must be at least one independent member on the board. The better-governed system reduces both agency conflicts and enhances firm value.Originality/valueA number of studies have already been undertaken by multiple investigators to build connection among CG with firm performance, but there is not even a single study in the literature that considers CG, firm value, firm Risk and discretionary earning management as a whole in one model to generalize its results in the emerging economy of Pakistan. A fundamental element of current analyzation process addresses that this is the very first graft of study conducted in Pakistan having combination of four variables together in one revision. There is minimal work that focuses on moderating effects of earning management on the CG-value and CG-risk relationships. This study uses two standard measures of firm performance (i.e. ROA and Tobin’s Q), one proxy of earning management (DEM) and three attributes of CG (board size, audit quality and ownership structure). Previously, researchers have not investigated a model that combines variables (CG as independent and Firm performance and Firm Risk as dependent along with DEM as moderator) in a single study.
LFOPI controller: a fractional order PI controller based load frequency control in two area multi-source interconnected power system
Authors: Sharma Deepesh , Yadav Naresh Kumar 
Published: April 2020

PurposeIn computer application scenario, data mining task is rarely utilized in power system, as an enhanced part, this work presented data mining task in power systems, to overcome frequency deviation issues. Load frequency control (LFC) is a primary challenging problem in an interconnected multi-area power system.Design/methodology/approachThis paper adopts lion algorithm (LA) for the LFC of two area multi-source interconnected power systems. The LA calculates the optimal gains of the fractional order PI (FOPI) controller and hence the proposed LA-based FOPI controller (LFOPI) is developed.FindingsFor the performance analysis, the proposed algorithm compared with various algorithm is given as, 80.6% lesser than the FOPI algorithm, 2.5% lesser than the GWO algorithm, 2.5% lesser than the HSA algorithm, 4.7% lesser than the BBO algorithm, 1.6% lesser than PSO algorithm and 80.6% lesser than the GA algorithm.Originality/valueThe LFOPI controller is the proposed controlling method, which is nothing but the FOPI controller that gets the optimal gain using the LA. This method produces better performance in terms of converging behavior, optimization of controller gain, transient profile and steady-state response.