bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of 19 antiviral drugs against SARS-CoV-2 Infection
Authors: Liu Shufeng , Lien Christopher Z. , Selvaraj Prabhuanand , Wang Tony T. 
Published: April 2020

AbstractThe global pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has prompted multiple clinical trials to jumpstart search for anti-SARS-CoV-2 therapies from existing drugs, including those with reportedin vitroefficacies as well as those ones that are not known to inhibit SARS-CoV-2, such as ritonavir/lopinavir and favilavir. Here we report that after screening 19 antiviral drugs that are either in clinical trials or with proposed activity against SARS-CoV-2, remdesivir was the most effective. Chloroquine only effectively protected virus-induced cytopathic effect at around 30 µM with a therapeutic index of 1.5. Our findings also suggest that velpatasvir, ledipasvir, ritonavir, litonavir, lopinavir, favilavir, sofosbuvir, danoprevir, and pocapavir do not have direct antiviral effect.
Mass spectrometry analysis of newly emerging coronavirus HCoV-19 spike S protein and human ACE2 reveals camouflaging glycans and unique post-translational modifications
Authors: Sun Zeyu , Ren Keyi , Zhang Xing , Chen Jinghua , Jiang Zhengyi , Jiang Jing , Ji Feiyang , Ouyang Xiaoxi , Li Lanjuan 
Published: April 2020

AbstractThe pneumonia-causing COVID-19 pandemia has prompt worldwide efforts to understand its biological and clinical traits of newly identified HCoV-19 virus. In this study, post-translational modification (PTM) of recombinant HCoV-19 S and hACE2 were characterized by LC-MSMS. We revealed that both proteins were highly decorated with specific proportions of N-glycan subtypes. Out of 21 possible glycosites in HCoV-19 S protein, 20 were confirmed completely occupied by N-glycans, with oligomannose glycans being the most abundant type. All 7 possible glycosylation sites in hACE2 were completely occupied mainly by complex type N-glycans. However, we showed that glycosylation did not directly contribute to the binding affinity between SARS-CoV spike protein and hACE2. Additionally, we also identified multiple sites methylated in both proteins, and multiple prolines in hACE2 were converted to hydroxylproline. Refined structural models were built by adding N-glycan and PTMs to recently published cryo-EM structure of the HCoV-19 S and hACE2 generated with glycosylation sites in the vicinity of binding surface. The PTM and glycan maps of both HCoV-19 S and hACE2 provide additional structural details to study mechanisms underlying host attachment, immune response mediated by S protein and hACE2, as well as knowledge to develop remedies and vaccines desperately needed nowadays.
Intra-species signaling betweenPseudomonas aeruginosagenotypes increases production of quorum sensing controlled virulence factors
Authors: Mould Dallas L. , Botelho Nico J. , Hogan Deborah A. 
Published: April 2020

AbstractThe opportunistic pathogenPseudomonas aeruginosadamages hosts through the production of diverse secreted products, many of which are regulated by quorum sensing. ThelasRgene, which encodes a central quorum-sensing regulator, is frequently mutated, and loss of LasR function impairs the activity of downstream regulators RhlR and PqsR. We found that in diverse models, the presence ofP. aeruginosawild type causes LasR loss-of-function strains to hyperproduce RhlR/I-regulated antagonistic factors, and autoinducer production by the wild type is not required for this effect. We uncovered a reciprocal interaction between isogenic wild type andlasRmutant pairs wherein the iron-scavenging siderophore pyochelin, specifically produced by thelasRmutant, induces citrate release and cross-feeding from wild type. Citrate stimulates RhlR signaling and RhlI levels in LasR-but not in LasR+ strains, and the interactions occur in diverse media. Co-culture interactions between strains that differ by the function of a single transcription factor may explain worse outcomes associated with mixtures of LasR+ and LasR loss-of-function strains. More broadly, this report illustrates how interactions within a genotypically diverse population, similar to those that frequently develop in natural settings, can promote net virulence factor production.
A Cytoskeletal Protein Complex is Essential for Division of Intracellular Amastigotes ofLeishmania mexicana
Authors: Kelly Felice D. , Tran Khoa D. , Hatfield Jess , Schmidt Kat , Sanchez Marco A. , Landfear Scott M. 
Published: April 2020

AbstractPrevious studies inLeishmania mexicanahave identified the cytoskeletal protein KHARON as being important for both flagellar trafficking of the glucose transporter GT1 and for successful cytokinesis and survival of infectious amastigote forms inside mammalian macrophages. KHARON is located in three distinct regions of the cytoskeleton: the base of the flagellum, the subpellicular microtubules, and the mitotic spindle. To deconvolve the different functions for KHARON, we have identified two partner proteins, KHAP1 and KHAP2, that associate with KHARON. KHAP1 is located only in the subpellicular microtubules, while KHAP2 is located at the subpellicular microtubules and the base of the flagellum. Both theKHAP1andKHAP2null mutants are unable to execute cytokinesis but are able to traffic GT1 to the flagellum. These results confirm that KHARON assembles into distinct functional complexes and that the subpellicular complex is essential for cytokinesis and viability of disease-causing amastigotes but not for flagellar membrane trafficking.
SARS-CoV-2 Spike S1 Receptor Binding Domain undergoes Conformational Change upon Interaction with Low Molecular Weight Heparins
Authors: Mycroft-West Courtney J. , Su Dunhao , Li Yong , Guimond Scott E. , Rudd Timothy R. , Elli Stefano , Miller Gavin , Nunes Quentin M. , Procter Patricia , Bisio Antonella , Forsyth Nicholas R. , Turnbull Jeremy E. , Guerrini Marco , Fernig David G. , Yates Edwin A. , Lima Marcelo A. , Skidmore Mark A. 
Published: April 2020

AbstractThe dependence of the host on the interaction of hundreds of extracellular proteins with the cell surface glycosaminoglycan heparan sulphate (HS) for the regulation of homeostasis is exploited by many microbial pathogens as a means of adherence and invasion. The closely related polysaccharide heparin, the widely used anticoagulant drug, which is structurally similar to HS and is a common experimental proxy, can be expected to mimic the properties of HS. Heparin prevents infection by a range of viruses when added exogenously, including S-associated coronavirus strain HSR1 and inhibits cellular invasion by SARS-CoV-2. We have previously demonstrated that unfractionated heparin binds to the Spike (S1) protein receptor binding domain, induces a conformational change and have reported the structural features of heparin on which this interaction depends. Furthermore, we have demonstrated that enoxaparin, a low molecular weight clinical anticoagulant, also binds the S1 RBD protein and induces conformational change. Here we expand upon these studies, to a wide range of low molecular weight heparins and demonstrate that they induce a variety of conformational changes in the SARS-CoV-2 RBD. These findings may have further implications for the rapid development of a first-line therapeutic by repurposing low molecular weight heparins, as well as for next-generation, tailor-made, GAG-based antiviral agents, against SARS-CoV-2 and other members of theCoronaviridae.
Activity profiling and structures of inhibitor-bound SARS-CoV-2-PLpro protease provides a framework for anti-COVID-19 drug design
Authors: Rut Wioletta , Lv Zongyang , Zmudzinski Mikolaj , Patchett Stephanie , Nayak Digant , Snipas Scott J. , El Oualid Farid , Huang Tony T. , Bekes Miklos , Drag Marcin , Olsen Shaun K. 
Published: April 2020

AbstractIn December 2019, the first cases of a novel coronavirus infection causing COVID-19 were diagnosed in Wuhan, China. Viral Papain-Like cysteine protease (PLpro, NSP3) is essential for SARS-CoV-2 replication and represents a promising target for the development of antiviral drugs. Here, we used a combinatorial substrate library containing natural and a wide variety of nonproteinogenic amino acids and performed comprehensive activity profiling of SARS-CoV-2-PLpro. On the scaffold of best hits from positional scanning we designed optimal fluorogenic substrates and irreversible inhibitors with a high degree of selectivity for SARS PLpro variants versus other proteases. We determined crystal structures of two of these inhibitors (VIR250 and VIR251) in complex with SARS-CoV-2-PLpro which reveals their inhibitory mechanisms and provides a structural basis for the observed substrate specificity profiles. Lastly, we demonstrate that SARS-CoV-2-PLpro harbors deISGylating activities similar to SARS-CoV-1-PLpro but its ability to hydrolyze K48-linked Ub chains is diminished, which our sequence and structure analysis provides a basis for. Altogether this work has revealed the molecular rules governing PLpro substrate specificity and provides a framework for development of inhibitors with potential therapeutic value or drug repositioning.
How mutations of intrinsically disordered protein regions can drive cancer
Authors: Mészáros Bálint , Hajdu-Soltész Borbála , Zeke András , Dosztányi Zsuzsanna 
Published: April 2020

AbstractMany proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered proteins/protein regions (IDPs/IDRs) driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. The detailed analysis of these IDRs revealed that they can function in multiple ways that are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks independently of the modulation of globular proteins. Disordered drivers are also highly relevant at the sample level, and their mutations can represent the key driving event in certain individual cancer patients. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options.
HPC-REDItools: a Novel HPC-aware Tool for Improved Large Scale RNA-editing Analysis
Authors: Flati Tiziano , Gioiosa Silvia , Spallanzani Nicola , Tagliaferri Ilario , Diroma Maria Angela , Pesole Graziano , Chillemi Giovanni , Picardi Ernesto , Castrignanò Tiziana 
Published: April 2020

AbstractBackgroundRNA editing is a widespread co-/post-transcriptional mechanism that alters primary RNA sequences through the modification of specific nucleotides and it can increase both the transcriptome and proteome diversity. The automatic detection of RNA-editing from RNA-seq data is computational intensive and limited to small data sets, thus preventing a reliable genome-wide characterisation of such process.ResultsIn this work we introduce HPC-REDItools, an upgraded tool for accurate RNA-editing events discovery from large dataset repositories. Availability:https://github.com/BioinfoUNIBA/REDItools2.ConclusionsHPC-REDItools is dramatically faster than the previous version, REDItools, enabling big-data analysis by means of a MPI-based implementation and scaling almost linearly with the number of available cores.
Cathodic protection criteria of low alloy steel in simulated deep water environment
Authors: Sun Haijing , Xue Weihai , Xu Jiaxin , Chen Guoliang , Sun Jie 
Published: April 2020

Purpose
The purpose of this work is to provide theoretical guidance and experimental analysis for optimized cathodic protection (CP) design of low alloy steel in deep water environments.

Design/methodology/approach
In the present study, the CP criteria of 10Ni5CrMoV low alloy steel were investigated in a simulated deep water environment (350 m) regarding the theoretical protection potential and measured protection potential. The influences of hydrostatic pressure (HP) and temperature were also discussed in detail. The theoretical protection potential was analyzed with the Nernst equation, and the measured minimum protection potential was derived by extrapolating the Tafel portion of anodic polarization curves.

Findings
The results indicate that the minimum protection potential of low alloy steel shifts to a positive value in a deep-ocean environment. This can be attributed to the combined effects of HP and the temperature. Moreover, the temperature has a stronger influence compared with HP. The results suggest that the CP potential criteria used in shallow water are still applicable in the deep ocean, which is further confirmed through the SEM and x-ray diffraction analysis of the corrosion products resulted from the potentiostatic cathodic polarization experiments at −0.85 VCSE.

Originality/value
In recent decades, successful applications of CP for long-term corrosion protection of the steel components applied at a subsea level have enabled the offshore industry to develop reliable and optimized CP systems for shallow water. However, differences in the seawater environment at greater depths have raised concerns regarding the applicability of the existing CP design for deeper water environments. Hence, this research focuses on the CP criteria of low alloy steel in simulated deep water environment concerning the theoretical protection potential and measured protection potential. The influences of HP and temperature were also discussed.
Corporate listening: unlocking insights from VOC, VOE and VOS for mutual benefits
Authors: Macnamara Jim 
Published: April 2020

PurposeComparatively, while the voice of customers, employees, and other stakeholders have been identified as key components of corporate and marketing communication, little attention has been paid to how organizations listen to, make sense of, and use the information provided. The research reported in this article examined how a multinational corporation and its subsidiaries listen to their customers, employees, and other stakeholders and explored how corporate listening can be improved for mutual benefits.Design/methodology/approachThis article reports participatory action research within a multinational corporation operating in Europe, Canada and Australia, which set out to become a “listening organization” to improve its relationships and performance. The research was informed by interviews, observation, content analysis of relevant documents, and critical reflection.FindingsThis analysis illustrates the need for and benefits of looking beyond statistical data to analyze textual, aural and visual data available from call centers, open-end survey comments, complaints, correspondence, social media and other sources, and it identifies methods, tools and technologies for ethical insightful corporate listening.Research limitations/implicationsThis article advocates a “turn” from a focus on voice to focus on listening, noting that expression of the voice of customers, employees and other stakeholders has no value to them or organizations without active listening.Originality/valueThis paper reports an in-depth study of corporate listening to multiple stakeholders and identifies opportunities for increased insights and understanding that can lead to tangible benefits for both organizations and their stakeholders.
Relationship between self-efficacy and knowledge sharing: systematic review
Authors: Safdar Muhammad , Batool Syeda Hina , Mahmood Khalid 
Published: April 2020

Purpose
The purpose of this paper was to systematically collect and review the research studies that provide empirical evidence regarding the existence of relationship between self-efficacy and knowledge sharing or influence of self-efficacy on sharing of knowledge.

Design/methodology/approach
The studies were collected through searching in Google Scholar, Scopus, ProQuest Dissertations and Theses, LISTA (Library, Information Science and Technology Abstracts) and Web of Science. All types of studies, except books, were selected for review. Time limitation was not applied.

Findings
It can be concluded from majority of reviewed studies that self-efficacy influenced knowledge sharing. This systematic review also establishes that majority of reviewed studies confirmed existence of relationship (positive) between variables self-efficacy and knowledge sharing.

Research limitations/implications
A language limit was applied, and only English language studies were reviewed.

Originality/value
This review is first of its kind that systematically collected and reviewed the studies that examined the relationship between self-efficacy and knowledge sharing. This paper is also first in terms of a study which systematically collected and reviewed studies that investigated impact of self-efficacy on sharing of knowledge. Findings of current research paper will be helpful for organizations striving to implement a knowledge-sharing culture. Similarly, this study will also help the readers in understanding the ways to improve their knowledge-sharing practices and learning.
A novel steady-state maintenance simulation framework for multi- information disseminations in crowd network
Authors: Wang Zhong , Sun Hongbo , Fan Baode 
Published: April 2020

PurposeThe era of crowd network is coming and the research of its steady-state is of great importance. This paper aims to establish a crowd network simulation platform and maintaining the relative stability of multi-source dissemination systems.Design/methodology/approachWith this simulation platform, this paper studies the characteristics of “emergence,” monitors the state of the system and according to the fixed point judges the system of steady-state conditions, then uses three control conditions and control methods to control the system status to acquire general rules for maintain the stability of multi-source information dissemination systems.FindingsThis paper establishes a novel steady-state maintenance simulation framework. It will be useful for achieving controllability to the evolution of information dissemination and simulating the effectiveness of control conditions for multi-source information dissemination systems.Originality/valueThis paper will help researchers to solve problems of public opinion control in multi-source information dissemination in crowd network.
The role of stakeholders in shifting environmental practices of music festivals in British Columbia, Canada
Authors: Hazel Dominique , Mason Courtney 
Published: April 2020

PurposeThe purpose of this paper is to increase understandings of the complexity of stakeholder relationships and their impact on environmental practices in music festivals in Western Canada, but also to highlight how managers can leverage their festival platform for stakeholders to create new partnerships that foster and support primary values around sustainability.Design/methodology/approachWe use a community-based participatory framework to guide this study, and qualitative research methods in the form of in-depth interviews and surveys at three separate music festivals within the interior of British Columbia, Canada.FindingsThe majority of patrons are aware of the environmental impacts of music festivals and are more likely to attend a festival with effective practices. By making environmental sustainability a core value of the festival and communicating environmental objectives with both stakeholders and patrons, managers can begin to alleviate the operational barriers to environmentalism.Originality/valueOne of the primary contributions of this study is that it provides management with deeper understandings of a wide range of barriers to effective environmental practices in Western Canada. We consult directly with both festival management and attendees about environmental practices. This paper presents a fuller perspective of how to move beyond simple measures and craft a more sophisticated and flexible environmental strategy that reduces risk, anticipates obstacles and greatly improves the odds of successful implementation.
Tasks mapping in the network on a chip using an improved optimization algorithm
Authors: Darbandi Mehdi , Ramtin Amir Reza , Sharafi Omid Khold 
Published: April 2020

Purpose
A set of routers that are connected over communication channels can from network-on-chip (NoC). High performance, scalability, modularity and the ability to parallel the structure of the communications are some of its advantages. Because of the growing number of cores of NoC, their arrangement has got more valuable. The mapping action is done based on assigning different functional units to different nodes on the NoC, and the way it is done contains a significant effect on implementation and network power utilization. The NoC mapping issue is one of the NP-hard problems. Therefore, for achieving optimal or near-optimal answers, meta-heuristic algorithms are the perfect choices. The purpose of this paper is to design a novel procedure for mapping process cores for reducing communication delays and cost parameters. A multi-objective particle swarm optimization algorithm standing on crowding distance (MOPSO-CD) has been used for this purpose.

Design/methodology/approach
In the proposed approach, in which the two-dimensional mesh topology has been used as base construction, the mapping operation is divided into two stages as follows: allocating the tasks to suitable cores of intellectual property; and plotting the map of these cores in a specific tile on the platform of NoC.

Findings
The proposed method has dramatically improved the related problems and limitations of meta-heuristic algorithms. This algorithm performs better than the particle swarm optimization (PSO) and genetic algorithm in convergence to the Pareto, producing a proficiently divided collection of solving ways and the computational time. The results of the simulation also show that the delay parameter of the proposed method is 1.1 per cent better than the genetic algorithm and 0.5 per cent better than the PSO algorithm. Also, in the communication cost parameter, the proposed method has 2.7 per cent better action than a genetic algorithm and 0.16 per cent better action than the PSO algorithm.

Originality/value
As yet, the MOPSO-CD algorithm has not been used for solving the task mapping issue in the NoC.