bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive variant effect predictions of single nucleotide variants in model organisms
Authors: Wagih Omar , Busby Bede , Galardini Marco , Memon Danish , Typas Athanasios , Beltrao Pedro 
Published: May 2018

AbstractThe effect of single nucleotide variants (SNVs) in coding and non-coding regions is of great interest in genetics. Although many computational methods aim to elucidate the effects of SNVs on cellular mechanisms, it is not straightforward to comprehensively cover different molecular effects. To address this we compiled and benchmarked sequence and structure-based variant effect predictors and we analyzed the impact of nearly all possible amino acid and nucleotide variants in the reference genomes of H. sapiens, S. cerevisiae and E. coli. Studied mechanisms include protein stability, interaction interfaces, post-translational modifications and transcription factor binding sites. We apply this resource to the study of natural and disease coding variants. We also show how variant effects can be aggregated to generate protein complex burden scores that uncover protein complex to phenotype associations based on a set of newly generated growth profiles of 93 sequenced S. cerevisiae strains in 43 conditions. This resource is available through mutfunc, a tool by which users can query precomputed predictions by providing amino acid or nucleotide-level variants.
Drug repurposing: omeprazole increases the efficacy of acyclovir against herpes simplex virus type 1 and 2
Authors: Michaelis Martin , Kleinschmidt Malte Christian , Wass Mark N. , Cinatl Jindrich 
Published: May 2018

AbstractObjectivesOmeprazole was shown to improve the anti-cancer effect of the nucleoside-analogue 5-fluorouracil. Here, we investigated the effects of omeprazole on the activities of the antiviral nucleoside analogues ribavirin and acyclovir.MethodsWest Nile virus-infected Vero cells and influenza A H1N1-infected MDCK cells were treated with omeprazole and/ or ribavirin. Herpes simplex virus 1 (HSV-1)- or HSV-2-infected Vero or HaCat cells were treated with omeprazole and/ or acyclovir. Antiviral effects were determined by examination of cytopathogenic effects (CPE), immune staining, and virus yield assay. Cell viability was investigated by MTT assay.ResultsOmeprazole concentrations up to 80μg/mL did not affect the antiviral effects of ribavirin. In contrast, omeprazole increased the acyclovir-mediated effects on HSV-1- and HSV-2-induced CPE formation in a dose-dependent manner in Vero and HaCat cells. Addition of omeprazole 80μg/mL resulted in a 10.8-fold reduction of the acyclovir concentration that reduces CPE formation by 50% (IC50) in HSV-1-infected Vero cells and in a 47.7-fold acyclovir IC50 reduction in HSV-1-infected HaCat cells. In HSV-2-infected cells, omeprazole reduced the acyclovir IC50 by 7.3-fold (Vero cells) or by 12.9-fold (HaCat cells). Omeprazole also enhanced the acyclovir-mediated effects on viral antigen expression and virus replication in HSV-1- and HSV-2-infected cells. In HSV-1-infected HaCat cells, omeprazole 80μg/mL reduced the virus titre in the presence of acyclovir 1μg/mL by 1.6×105-fold. In HSV-2-infected HaCat cells omeprazole 80μg/mL reduced the virus titre in the presence of acyclovir 2μg/mL by 9.2×103-fold. The investigated drug concentrations did not affect cell viability, neither alone nor in combination.ConclusionsOmeprazole increases the anti-HSV activity of acyclovir. As clinically well-established and tolerated drug, it is a candidate drug for antiviral therapies in combination with acyclovir.
A Genome-Wide Association Analysis Reveals a Role for Recombination in the Evolution of Antimicrobial Resistance in Burkholderia multivorans
Authors: Diaz Caballero Julio , Clark Shawn T. , Wang Pauline W. , Donaldson Sylva L. , Coburn Bryan , Tullis D. Elizabeth , Yau Yvonne C.W. , Waters Valerie J. , Hwang David M. , Guttman David S. 
Published: May 2018

AbstractCystic fibrosis (CF) lung infections caused by members of the Burkholderia cepacia complex, such as Burkholderia multivorans, are associated with high rates of mortality and morbidity. We performed a population genomic study of 111 B. multivorans sputum isolates from a single CF patient through three stages of infection including the initial incident infection, deep sampling of a one-year period of chronic infection, and deep sampling of a post-transplant recolonization. We reconstructed the evolutionary history of the population and used a lineage-controlled genome-wide association study (GWAS) approach to identify genetic variants associated with antibiotic resistance. We found that the incident isolate was more susceptible to agents from three antimicrobial classes (β-lactams, aminoglycosides, quinolones), while the chronic isolates diversified into distinct genetic lineages with reduced antimicrobial susceptibility to the same agents. The post-transplant reinfection isolates displayed genetic and phenotypic signatures that were distinct from sputum isolates from all CF lung specimens. There were numerous examples of parallel pathoadaptation, in which individual loci, or even the same codon, were independently mutated multiple times. This set of loci was enriched for functions associated with virulence and resistance. Our GWAS approach identified one variant in the ampD locus (which was independently mutated four times in our dataset) associated with resistance to β-lactams, and two non-synonymous polymorphisms associated with resistance to both aminoglycosides and quinolones, affecting an araC family transcriptional regulator, which was independently mutated three times, and an outer member porin, which was independently mutated twice. We also performed recombination analysis and identified a minimum of 14 recombination events. Parallel pathoadaptive loci and polymorphisms associated with β-lactam resistance were over-represented in these recombinogenic regions. This study illustrates the power of deep, longitudinal sampling coupled with evolutionary and lineage-corrected GWAS analyses to reveal how pathogens adapt to their hosts.
A Rice Glutamyl-tRNA Synthetase Modulates Early Anther Cell Division and Patterning
Authors: Yang Xiujuan , Li Gang , Tian Yuesheng , Song Yu , Liang Wanqi , Zhang Dabing 
Published: May 2018

Abstract
Aminoacyl-tRNA synthetases (aaRSs) have housekeeping roles in protein synthesis, but little is known about how these aaRSs are involved in organ development. Here, we report that a rice (Oryza sativa) glutamyl-tRNA synthetase (OsERS1) maintains proper somatic cell organization and limits the overproliferation of male germ cells during early anther development. The expression of OsERS1 is specifically detectable in meristematic layer 2-derived cells of the early anther, and osers1 anthers exhibit overproliferation and disorganization of layer 2-derived cells, producing fused lobes and extra germ cells in early anthers. The conserved biochemical function of OsERS1 in ligating glutamate to tRNAGlu is enhanced by its cofactor aaRS OsARC. Furthermore, metabolomics profiling revealed that OsERS1 is an important node for multiple metabolic pathways, indicated by the accumulation of amino acids and tricarboxylic acid cycle components in osers1 anthers. Notably, the anther defects of the osers1 mutant are causally associated with the abnormal accumulation of hydrogen peroxide, which can reconstitute the osers1 phenotype when applied to wild-type anthers. Collectively, these findings demonstrate how aaRSs affect male organ development in plants, likely through protein synthesis, metabolic homeostasis, and redox status.
Being the change: charting Greg de Hoedt’s cannabis journey
Authors: Bone Melissa , de Hoedt Greg 
Published: May 2018

Purpose
The purpose of this paper is to document a leading UK cannabis activist’s efforts to bring about policy change and to convey his human story as a medical consumer. The paper contends that it is not enough to present evidence-based policies to effect change in drug policy, it is also vital to tell human stories, which people can relate to, in order to develop narratives which speak to people’s values.

Design/methodology/approach
An in depth, unstructured interview was conducted between Dr Melissa Bone and Cannabis Activist, Greg de Hoedt in December 2017. The interview was recorded, transcribed and formed the basis of the paper, which was co-edited and co-created by both authors.

Findings
The paper charts Greg’s journey from being a cannabis consumer – to being diagnosed with Crohn’s – to being a cannabis activist. The paper interweaves a drug policy discussion with a personal narrative. It connects unique insights into Greg’s life with the broader forces and institutions which influence cannabis policy at a local, national and international level.

Originality/value
Incorporating Greg’s personal narrative within an academic platform integrates his experiential knowledge into the “expert” evidence base. Alongside the potential of personal narratives to facilitate the production of knowledge, Greg’s emotive story could help to shape the public’s perception of cannabis, which could subsequently influence policy.
Strategic competences for pricing quantity surveying consultancy services
Authors: Adesi Michael , Owusu-Manu De-Graft , Murphy Roisin 
Published: May 2018

Purpose
Professional quantity surveying (QS) services are critical to successful delivery of construction projects within planned budget, quality and duration. The supply of QS professional services is largely dependent on the price level of services and the willingness of clients to pay. The pricing of professional QS consultancy services has been confronted with a myriad of pricing challenges due to rapid changes in the business environment; the pervasive influence of information technology; and the complexity of clients’ expectation. It is therefore necessary for QS consultancy firms to develop strategic competences for the pricing of their services. In addition, numerous studies have not given the pricing the pricing of professional services the requisite attention. The purpose of this paper is to investigate the strategic competences for pricing professional QS services.

Design/methodology/approach
The study was positioned within the positivist tradition. As a result, the quantitative approach was adopted using a survey questionnaire to collect data from QS consultants. The sample size of the study was 79 professional quantity surveyors chosen by using simple random sampling technique from a population of 372 registered professional QS of the Ghana Institution of Surveyors. Using the χ2 test and factor analysis, the study established relationship between strategic competences and pricing of QS services.

Findings
The study found that strategic competences for pricing QS professional services is significantly related to the managerial and professional competence of QS consultants. The strategic competences of QS consultants identified by this study include business management, services cost management; and production capabilities.

Practical implications
This study provides an empirical basis for QS consultancy firms to focus on strategic direction of their contractual arrangement with clients. Practically, resource configuration and on strategic competences for professional service pricing would create price leadership.

Originality/value
The study advances the pricing knowledge within the QS practice by demonstrating the nexus between strategic competences and the pricing of QS professional services which hitherto this study have not been effectively investigated.
English education as democratic armor
Authors: Gatti Lauren , Masterson Jessica , Brooke Robert , Shah Rachael W. , Thomas Sarah 
Published: May 2018

PurposeThe purpose of this paper is to illustrate the ways in which attention to programmatic vision and coherence – rather than foci on individual courses – might advance the work of justice-oriented, critical English education in important ways. The authors propose that consciously attending to the work of English education on the programmatic level can better enable English educators to cultivate democracy-sustaining dispositions in preservice teachers. Using Grossman et al.’s (2008) definition of “programmatic coherence”, the authors illustrate how one interdepartmental partnership is working to create a shared programmatic vision for English education.Design/methodology/approachDrawing on Cornel West’s call for the development of a three-piece democratic armor – Socratic questioning, prophetic witness and tragicomic hope – the authors describe their programmatic vision for cultivating democracy-sustaining dispositions in preservice teachers. They show how this shared vision constitutes the foundation for the organization, purpose and sequence of the four-semester cohort program. Finally, the authors describe how this vision helps facilitate meaningful and purposeful symbiosis between field experiences and university coursework.FindingsIn an effort to promote replicability regarding programmatic coherence, the authors share structural aspects of their program as well as pose generative questions for colleagues who are interested in approaching the work of critical, democratic English education from the programmatic level.Originality/valueAddressing the challenges of teacher preparation – especially in this polarized and pitched historical moment – requires shifting the focus from individual courses to a more expansive view that might enable English educators to consider how courses within a program mightcollectivelyadvance a particular vision of critical and democratic English education.
Personal Web Library: organizing and visualizing Web browsing history
Authors: Du Weidan , Qian Zhenyu Cheryl , Parsons Paul , Chen Yingjie Victor 
Published: May 2018

Purpose
Modern Web browsers all provide a history function that allows users to see a list of URLs they have visited in chronological order. The history log contains rich information but is seldom used because of the tedious nature of scrolling through long lists. This paper aims to propose a new way to improve users’ Web browsing experience by analyzing, clustering and visualizing their browsing history.

Design/methodology/approach
The authors developed a system called Personal Web Library to help users develop awareness of and understand their Web browsing patterns, identify their topics of interest and retrieve previously visited Web pages more easily.

Findings
User testing showed that this system is usable and attractive. It found that users can easily see patterns and trends at different time granularities, recall pages from the past and understand the local context of a browsing session. Its flexibility provides users with much more information than the traditional history function in modern Web browsers. Participants in the study gained an improved awareness of their Web browsing patterns. Participants mentioned that they were willing to improve their time management after viewing their browsing patterns.

Practical implications
As more and more daily activities rely on the internet and Web browsers, browsing data captures a large part of users’ lives. Providing users with interactive visualizations of their browsing history can facilitate personal information management, time management and other meta-level activities.

Originality/value
This paper aims to help users gain insights into and improve their Web browsing experience, the authors hope that the work they conducted can spur more research contributions in this underdeveloped yet important area.
The dynamics of proximity in multiple-party innovation processes
Authors: Öberg Christina 
Published: May 2018

Purpose
Proximity – that is, the closeness of parties – has been increasingly emphasized in studies on innovation networks. The idea of closeness has been discussed in relation to geographic proximity, and has also been referred to as knowledge overlaps and shared understandings between parties. In most of the studies dealing with proximity in relation to innovation networks, a static analysis is pursued. Such an analysis marks how the closeness or distance, often with the conclusion that parties should not be too close or too distant, is measured against innovation outcome at a specific point in time. However, innovation processes would include how parties increasingly converge in their knowledge and understanding, and how they may co-locate their businesses. The purpose of this paper is to discuss proximity in relation to multiple-party innovation processes and their development over time.

Design/methodology/approach
The empirical part of this paper consists of a single case study on an innovation community and its development process. The development of the innovation community over time, whether and how geographic, knowledge and cognitive proximity is affected, and the outcome in terms of number of innovations, their newness (incremental or radical innovation), and variety are discussed in the paper.

Findings
Findings indicate how geographic proximity leads to more knowledge overlaps, while it is not a prerequisite for it. Rather, it is in the commitment processes partly connected to cognitive proximity that knowledge increasingly converges, indifferent to the co-location of parties. The speed of such processes, however, is higher if parties co-locate. The commitment processes lead to an increased number of innovations, while these innovations become more and more similar. To avoid increased overlaps of knowledge and thereby maintain the production of a variety of innovations, interaction needs to occur through the introduction of new parties and the termination of previous interaction patterns. This, however, occurs at the cost of commitment, and the knowledge thereby becomes less developed and used in its capacities.

Originality/value
The paper contributes to previous research through discussing proximity in innovation networks in a processual manner. The link between various proximities and their effect on innovation outcome sheds light on how proximity, as discussed in various literature streams, often relates to similar issues that converge around the issue of commitment.
Facebook users’ loneliness based on different types of interpersonal relationships
Authors: Lim Myung Suh , Kim Junghyun 
Published: May 2018

Purpose
The purpose of this paper is to investigate: first, the effects of a user’s grandiosity on the loneliness of another user on Facebook who detected it in terms of his/her well-being status; second, the mediational role of envy between grandiosity and loneliness; and, third, whether different effects are given on narcissism, envy, and loneliness depending on social or para-social relationships on Facebook.

Design/methodology/approach
This study’s focus is to investigate how observing others’ grandiose behaviors impact on individuals’ feeling of loneliness. The authors propose that this relationship is mediated by the feeling of envy. The authors further postulate that social relationships that participants may have with other Facebook users would play a key role in feeling different types of envy (i.e. malicious vs benign). Therefore, the current study employed a 2 (levels of grandiosity: high vs low) × 2 (social relationship: para-social vs social) between-subjects design.

Findings
The authors found that one’s grandiosity as reflected on Facebook significantly affects other users’ loneliness through malicious envy. However, no moderated mediation via envy (either benign or malicious) was found within the social relationship group.

Originality/value
Social comparison generated by the use of Facebook was found to have an effect on the user’s loneliness through the mediation of envy. In particular, the possibility that such effects could be triggered in para-social relationships was identified.
The effects of knowledge management processes on human resource management
Authors: Zaim Halil , Keceli Yavuz , Jaradat Ashraf , Kastrati Selma 
Published: May 2018

Purpose
Managing knowledge effectively and efficiently is considered to be a key success factor to gain sustainable competitive advantage for organizations. This study aims to analyze the impact of knowledge management (KM) processes on human resource management (HRM).

Design/methodology/approach
To test the relationship of KM processes on HRM, a case study was conducted using structural equation modeling based on data collected from employees and managers of a Telecom company in Turkey. The survey instrument is a self-administered questionnaire composed of 37 questions. Three of them are demographic questions; 20 questions aim to reveal KM processes and 14 for HRM practices. The questionnaire was distributed via google survey link to employees and managers in headquarters office and two branches in Istanbul.

Findings
In this paper, the authors tried to investigate the impact of KM practices on the HRM performance of a company. The results indicate that companies with better KM practices tend to perform better at HRM. The main contribution of this paper lies in pointing out that, among the dimensions of KM, knowledge sharing and knowledge utilization have direct impact on HRM, whereas knowledge generation and knowledge sharing have indirect impacts.

Research limitations/implications
The main limitation of this study lies in the fact that data are collected from a single company in telecom industry. Therefore, it is difficult to generalize the results. Although the research findings are aligned with those of the previous studies, further research using data from numerous companies in various industries is still needed to generalize the research findings.

Practical implications
The paper includes implications for the development of knowledge utilization generated and stored within the company. The knowledge can create improvements in the company’s HRM performance if it is shared and used effectively. The paper addresses an important subject and the findings may be used by human resources and KM practitioners interested in the development of organizational knowledge through human resource practices.

Originality/value
This paper fulfills an identified need to investigate the impact of KM practices on the HRM performance of a company.
Between Devolution and Direct Rule: Implications of a Political Vacuum in Northern Ireland?
Authors: Heenan Deirdre , Birrell Derek 
Published: May 2018

AbstractIt is over a year since the collapse of the devolved administration at Stormont, which left one region of the United Kingdom without a functioning executive. Reluctance to introduce direct rule from Westminster reduced Northern Ireland to a desiccated form of governance. This article examines the nature and form of government in this political vacuum. The consequences of this system are examined in terms of the absence of legislation, mechanisms for scrutiny, and participation in intergovernmental relations. In the absence of devolution and direct rule, the potential for greater involvement of the Irish government in the affairs of Northern Ireland is also considered.
Reproductive Health: Morals, Margins and Rights
Authors: Scott Rosamund 
Published: May 2018

AbstractReproductive interventions and technologies have the capacity to generate profound societal unease and to provoke hostile reactions underpinned by various moral concerns. This paper shows that this position currently goes relatively unchecked by the European Court of Human Rights, which allows the margin of appreciation and consensus doctrines significantly to limit the scope of reproductive rights under the right to respect for private and family life under Article 8. This occurs both in relation to the interest in avoiding reproduction at stake in abortion, and that in achieving it at stake in medically assisted reproduction. The paper demonstrates significant flaws in the Court's framing and deployment of these doctrines in its reproductive jurisprudence. It argues that, as regards existing and upcoming reproductive interventions and technologies, the Court should attend to the concept of reproductive health, long recognised in international conventions and policy materials.