bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obstacles to Studying Alternative Splicing Using scRNA-seq
Authors: Westoby Jennifer , Artemov Pavel , Hemberg Martin , Ferguson-Smith Anne 
Published: October 2019

AbstractBackgroundEarly single-cell RNA-seq (scRNA-seq) studies suggested that it was unusual to see more than one isoform being produced from a gene in a single cell, even when multiple isoforms were detected in matched bulk RNA-seq samples. However, these studies generally did not consider the impact of dropouts or isoform quantification errors, potentially confounding the results of these analyses.ResultsIn this study, we take a simulation based approach in which we explicitly account for dropouts and isoform quantification errors. We use our simulations to ask to what extent it is possible to study alternative splicing using scRNA-seq. Additionally, we ask what limitations must be overcome to make splicing analysis feasible. We find that the high rate of dropouts associated with scRNA-seq is a major obstacle to studying alternative splicing. In mice and other well established model organisms, the relatively low rate of isoform quantification errors poses a lesser obstacle to splicing analysis. We find that different models of isoform choice meaningfully change our simulation results.ConclusionsTo accurately study alternative splicing with single-cell RNA-seq, a better understanding of isoform choice and the errors associated with scRNA-seq is required. An increase in the capture efficiency of scRNA-seq would also be beneficial. Until some or all of the above are achieved, we do not recommend attempting to resolve isoforms in individual cells using scRNA-seq.
Schizophrenia risk from locus-specific human endogenous retroviruses
Authors: Duarte Rodrigo R.R. , Bendall Matthew L. , de Mulder Miguel , Ormsby Christopher E. , Beckerle Greta A. , Selvackadunco Sashika , Troakes Claire , Reyes-Terán Gustavo , Crandall Keith A. , Srivastava Deepak P. , Nixon Douglas F. , Powell Timothy R. 
Published: October 2019

AbstractSchizophrenia genome-wide association studies highlight the substantial contribution of risk attributed to the non-coding genome where human endogenous retroviruses (HERVs) are encoded. These ancient viral elements have previously been overlooked in genetic and transcriptomic studies due to their poor annotation and repetitive nature. Using a new, comprehensive HERV annotation, we found that the fraction of the genome where HERVs are located (the ‘retrogenome’) is enriched for schizophrenia risk variants, and that there are 148 disparate HERVs involved in susceptibility. Analysis of RNA-sequencing data from the dorsolateral prefrontal cortex of 259 schizophrenia cases and 279 controls from the CommonMind Consortium showed that HERVs are actively expressed in the brain (n = 3,979), regulated in cis by common genetic variants (n = 1,759), and differentially expressed in patients (n = 81). Convergent analyses implicate LTR25_6q21 and ERVLE_8q24.3h as HERVs of etiological relevance to schizophrenia, which are co-regulated with genes involved in neuronal and mitochondrial function, respectively. Our findings provide a strong rationale for exploring the retrogenome and the expression of these locus-specific HERVs as novel risk factors for schizophrenia and potential diagnostic biomarkers and treatment targets.
A catalog of homoplasmic and heteroplasmic mitochondrial DNA variants in humans
Authors: Bolze Alexandre , Mendez Fernando , White Simon , Tanudjaja Francisco , Isaksson Magnus , Jiang Ruomu , Rossi Andrew Dei , Cirulli Elizabeth T. , Rashkin Misha , Metcalf William J. , Grzymski Joseph J. , Lee William , Lu James T. , Washington Nicole L. 
Published: October 2019

SummaryHigh quality population allele frequencies of DNA variants can be used to discover new biology, and study rare disorders. Here, we created a public catalog of mitochondrial DNA variants based on a population of 195,983 individuals. We focused on 3 criteria: (i) the population is not enriched for mitochondrial disorders, or other clinical phenotypes, (ii) all genomes are sequenced and analyzed in the same clinical laboratory, and (iii) both homoplasmic and heteroplasmic variants are reported. We found that 47% of the mitochondrial genome was invariant in this population, including large stretches in the 2 rRNA genes. This information could be used to annotate the mitochondrial genome in future studies. We also showed how to use this resource for the interpretation of pathogenic variants for rare mitochondrial disorders. For example, 42% of variants previously reported to be pathogenic for Leber Hereditary Optic Neuropathy (LHON) should be reclassified.
Cryo-EM structure of the mitochondrial protein-import channel TOM complex from Saccharomyces cerevisiae
Authors: Tucker Kyle , Park Eunyong 
Published: October 2019

AbstractNearly all mitochondrial proteins are encoded by the nuclear genome and imported into mitochondria following synthesis on cytosolic ribosomes. These precursor proteins are translocated into mitochondria by the TOM complex, a protein-conducting channel in the mitochondrial outer membrane. Using cryo-EM, we have obtained high-resolution structures of both apo and presequence-bound core TOM complexes from Saccharomyces cerevisiae in dimeric and tetrameric forms. Dimeric TOM consists of two copies each of five proteins arranged in two-fold symmetry—Tom40, a pore-forming β-barrel with an overall negatively-charged inner surface, and four auxiliary α-helical transmembrane proteins. The structure suggests that presequences for mitochondrial targeting insert into the Tom40 channel mainly by electrostatic and polar interactions. The tetrameric complex is essentially a dimer of dimeric TOM, which may be capable of forming higher-order oligomers. Our study reveals the molecular organization of the TOM complex and provides new insights about the mechanism of protein translocation into mitochondria.
Physical activity reduces colorectal cancer risk independent of BMI—A two-sample Mendelian randomisation study
Authors: Zhang Xiaomeng , Theodoratou Evropi , Li Xue , Farrington Susan M , Law Philip J , Broderick Peter , Walker Marion , Rees Jessica MB , Houlston Richard S , Tomlinson Ian PM , Campbell Harry , Dunlop Malcolm G , Timofeeva Maria 
Published: October 2019

AbstractBackgroundEvidence from observational studies suggests a protective role for physical activity (PA) against colorectal cancer (CRC) risk. However, it has yet to be established a causal relationship. We conducted a two-sample Mendelian randomisation (MR) study to examine causality between physical activity and CRC risk.MethodsWe used common genetic variants associated with self-reported and accelerometer-based physical activity as instrumental variables (IVs) in this MR study. The IVs were derived from the largest available genome-wide association study (GWAS) of physical activity, namely UK Biobank. We analysed the effect of the IVs for physical activity in a large CRC GWAS that included 31 197 cases and 61 770 controls. We applied inverse variance weighted (IVW) method as the main analysis method.ResultsOur results demonstrate a protective effect between accelerometer-based physical activity and CRC risk (the outlier-adjusted ORIVW was 0.92 per one standard deviation (SD) increase of accelerometer-base physical activity [95% CI: 0.87-0.98, P: 0.01]). The effect between self-reported physical activity and CRC risk was not statistically significant but was also supportive of an inverse association (the outlier-adjusted ORIVW was 0.61 per 1 SD increase of moderate-to-vigorous physical activity [95%CI: 0.36-1.06, P: 0.08]).ConclusionsThe findings of this large MR study show for the first time that objectively measured physical activity is causally implicated in reducing CRC risk. The limitations of the study are that it is based on only two genetic instruments and that it has limited power, despite the study size. Nonetheless, at a population level, these findings provide strong reinforcing evidence to support public health policy measures that encourage exercise, even in obese individuals.
Stop Codon Context Influences Genome-Wide Stimulation of Termination Codon Readthrough by Aminoglycosides
Authors: Wangen Jamie R , Green Rachel 
Published: October 2019

AbstractStop codon readthrough (SCR) occurs when the ribosome miscodes at a stop codon. Such readthrough events can be therapeutically desirable when a premature termination codon (PTC) is found in a critical gene. To study SCR in vivo in a genome-wide manner, we treated mammalian cells with aminoglycosides and performed ribosome profiling. We find that in addition to stimulating readthrough of PTCs, aminoglycosides stimulate readthrough of normal termination codons (NTCs) genome-wide. Stop codon identity, the nucleotide following the stop codon, and the surrounding mRNA sequence context all influence the likelihood of SCR. In comparison to NTCs, downstream stop codons in 3′UTRs are recognized less efficiently by ribosomes, suggesting that targeting of critical stop codons for readthrough may be achievable without general disruption of translation termination. Finally, we find that G418 treatment globally alters gene expression with substantial effects on translation of histone genes, selenoprotein genes, andS-adenosylmethionine decarboxylase (AMD1).
Smart management of the reconstruction process of post-conflict cities
Authors: Assem Ayman , Abdelmohsen Sherif , Ezzeldin Mohamed 
Published: October 2019

Purpose
Cities lying within conflict zones have continually faced hardships of both war aftermath and long-term sustainable reconstruction. Challenges have surpassed the typical question of recovery from post-conflict trauma, preserving urban heritage and iconic elements of the built environment, to face issues of critical decision making, rebuilding effectiveness and funding mechanisms, leading to time-consuming processes that lack adequate consistent long-term management. Some approaches have explored methods of effective long-term city reconstruction management but have not fully developed comprehensive approaches that alleviate the management of such complex processes. The paper aims to discuss these issues.

Design/methodology/approach
The authors devise an approach for the smart management of post-conflict city reconstruction. The authors focus on evaluation, strategic planning, reconstruction projects and implementation. The authors integrate building information modeling and geographic/geospatial information systems in a platform that allows for real-time analysis, reporting, strategic planning and decision making for managing reconstruction operations and projects among involved stakeholders including government agencies, funding organizations, city managers and public participants.

Findings
The approach suggested a smart management system for the reconstruction process of post-conflict cities. Implementing this system was shown to provide a multi-objective solution for post-conflict city reconstruction based on its interlinked modules.

Research limitations/implications
Results may lack generalizability and require testing on several cases to provide rigorous findings for different case studies.

Practical implications
Implications include developing smart management systems for use by city managers and government authorities in post-conflict zones, as well as bottom-up decision making by including participant citizens especially populations in the diaspora.

Originality/value
The approach offers an integrated platform that informs city reconstruction decision makers, allowing for strategic planning tools for efficient planning, monitoring tools for continuous management during and after reconstruction, and effective platforms for communication among all stakeholders.
Company values guiding the recruitment of employees with a foreign background
Authors: Lämsä Anna-Maija , Mattila Markku , Lähdesmäki Merja , Suutari Timo 
Published: October 2019

Purpose
In this paper, the following research question is addressed: Why do business organisations recruit employees with a foreign background? This was examined in terms of the values that guide organisations and their management. The paper aims to discuss this issue.

Design/methodology/approach
The study focused on two businesses in Finland that are pioneers in the recruitment of immigrants. A case study approach was adopted. The research data consist of interviews and documentary data. The data were analysed using content analysis in accordance with grounded theory.

Findings
Companies can act as an enabling force in the integration of immigrants into the local labour market, especially when the company’s value basis extends beyond only economic values.

Research limitations/implications
The study was conducted only in two case companies in Finland.

Practical implications
Companies have the potential to affect local people’s attitudes towards immigrants as workers. This is important because many western societies are likely to face a labour shortage in the future due to the ageing population and low birth rate.

Originality/value
Prior research has mostly investigated the topic from the viewpoints of the immigrants themselves and of policy makers. The value of this study is that it makes the employers’ viewpoint visible. The dominant theories applied in the field of immigrant recruitment are inadequate to explain employers’ behaviour because of their underlying assumption of the overwhelming importance of economic values in decision making.
Blue-collar workers, career success and innovation in manufacturing
Authors: Cillo Valentina , Garcia-Perez Alexeis , Del Giudice Manlio , Vicentini Francesca 
Published: October 2019

PurposeThe purpose of this paper is to contribute to the understanding of the relationship between employees’ knowledge and organisational performance.Design/methodology/approachUsing a structural equation model, feedback received from 237 blue-collar workers from multinational high-tech manufacturing enterprises in Italy was studied to understand, from a dynamic capabilities perspective, the role of soft skills in the career success of production workers.FindingsThe results of the analysis indicate a positive relationship between workers’ commitment to develop their soft skills and their career success, as well as a positive relationship between an organisation’s approach to both knowledge exploration and knowledge exploitation and the prospects for career success of blue-collar workers.Research limitations/implicationsThe research has both theoretical and practical implications, as any efforts by researchers and practitioners to find effective ways to motivate the workforce will be likely to lead to a positive attitude towards learning and, ultimately, to improved business performance.Originality/valueThe originality of the paper is the focus on the personality and interpersonal attributes of workforce – blue-collar workers – and how they can affect business performance in highly innovative contexts.
Exploring transdisciplinary approaches to facilitate disaster risk reduction
Authors: Matsuura Shohei , Razak Khamarrul Azahari 
Published: October 2019

Purpose
The purpose of this paper is to look into how collaborations among science and technology groups and other stakeholders in the Asia-Pacific region can facilitate implementation of national and local disaster risk reduction (DRR) strategies through education, training and field practice. Case studies on transdisciplinary approach (TDA) that integrates cross-cutting DRR issues and various stakeholders through science and technology are introduced from several countries in the region as attempts to holistically support societies build and strengthen their disaster resilience.

Design/methodology/approach
First, through literature review, the transition from single discipline to TDA is illustrated in which various stakeholders of different disciplines work together to achieve a common societal goal. This is followed by introduction of several case studies of actual TDA implementation for DRR in which information had been gathered through surveys and interviews with international science and technology stakeholders. Finally, through analysis and discussion, the study identifies the key roles of science and technology stakeholders for facilitating TDA for DRR.

Findings
The study concludes with key findings on the specific roles of science and technology including provision of education and training to build capacities of DRR practitioners to effectively plan and implement DRR measures, support to evidence-based decision making through locally specific scientific assessments and analysis and validation scientific information on the actual field for DRR practitioners and agencies. In materializing these roles into action, institutionalization of supporting policies and budget provision that promotes TDA are suggested.

Originality/value
Even though TDA is not a new concept and many stakeholders understand its importance, TDA has not been widely exercised mainly due to conventional practices of experts and organizations working only within their groups and disciplines. With this understanding, this study has newly identified eight key elements that can be used as a guide and checklist for DRR stakeholders to effectively implement TDA for strengthening disaster resilience of their societies.
Workers’ safety behaviors in the off-site manufacturing plant
Authors: Liu Qinjun , Ye Gui , Feng Yingbin 
Published: October 2019

Purpose
Although research on prefabricated construction has gained increasing attention in recent years, limited efforts have been devoted to investigating safety issues in the off-site manufacture, especially workers’ behavioral intentions to work safely. Thus, research is needed to identify the motivational factors determining off-site construction workers’ safety behaviors. The purpose of this paper is to investigate workers’ safety behavior by examining the determinants of behavioral intention in the off-site manufacturing plants in China.

Design/methodology/approach
Theory of planned behavior (TPB) was modified and used in this study to explain how the elements in the hypothesized model interact. Data were collected using a questionnaire. Structural equation modeling technique with partial least-squares estimation was used to analyze the data collected.

Findings
The findings of this study indicated that workers’ tendency to engage in safety behavior is positively related to attitude toward the behavior, subjective norm, perceived behavioral control and behavioral habit, among which attitude toward the behavior and behavioral habit have most significant influences on safety behavior. This finding provides a better explanation on the pathways and the impacts of the crucial factors on the safety behaviors for the off-site manufacture.

Originality/value
The possible innovation of this research lies in its attempt to understand the antecedents of workers’ safety behavior in the off-site construction environment, which may make original contributions to construction safety research and practice. The findings of this study contribute to the body of knowledge in TPB. Corresponding countermeasures are put forward in order to improve workers’ safety behavior in off-site construction.
An exploratory study on how SMEs are open to external sources of information
Authors: Idrissi Fakhreddine Moulay Othman , Castonguay Yan 
Published: October 2019

PurposeThe purpose of this paper is to draw on recent developments in the open innovation literature to explore whether the openness of SMEs to the four categories of external sources of information (ESI) is complementary, substitute or independent, while assessing the determinants of SMEs’ openness to these ESI.Design/methodology/approachThis research is based on data from a survey of 451 manufacturing SMEs in the province of Québec, Canada. Data have been elaborated through a multivariate probit model to empirically show that SMEs are considered to be simultaneously open to different ESI. The results of this study show significant heterogeneity in the determinants of SMEs’ openness to these ESI.FindingsThe study found that the SMEs’ openness to different ESI seems to be complementary rather than substitute; and not all variables included in the model explain the SMEs’ openness to the different ESI.Practical implicationsThe paper provides practical implications for managers and policy makers including the SMEs’ managers’ role to recognize the consolidation of different ESI jointly instead of separately. Furthermore, managers and policy makers should attempt to provide a fair context to SMEs to manage their openness ecosystem.Originality/valueThis study is virtually the first to investigate both the complementarity and the determinants of SMEs’ openness to different ESI using a sophisticated econometric model.
Entropy generation analysis of nanoliquid flow through microchannel considering heat source and different shapes of nanoparticle
Authors: Gireesha B.J. , Sindhu S. 
Published: October 2019

Purpose
This paper aims to focus on the steady state flow of nanoliquid through microchannel with the aid of internal heat source and different shapes of nanoparticle. The influence of MoS2 and TiO2 particles of nano size on flow and thermal fields is examined. The governing equations are modelled and then solved numerically. The obtained physical model is nondimensionalized using dimensionless quantities. The nondimensional equations are treated with numerical scheme. The outcome of the current work is presented graphically. Diverse substantial quantities such as entropy generation, Bejan number and Nusselt number for distinct parameters are depicted through graphs. The result established that nanoparticle of blade shape acquires larger thermal conductivity. Entropy analysis is carried out to explore the impact of various parameters such as nanoparticle volume fraction, magnetic parameter, radiation parameter and heat source parameter.

Design/methodology/approach
The resultant boundary value problem is converted into initial value problem using shooting scheme. Then the flow model is resolved using Runge-Kutta-Fehlberg-Fourth-Fifth order technique.

Findings
It is emphasized that entropy generation for the fluid satisfies N(ζ)(TiO2−water) > N(ζ)(MoS2−water). In addition to this, it is emphasized that N(ζ)sphere > N(ζ)brick > N(ζ)cylinder > N(ζ)platelet > N(ζ)blade. Also, it is obtained that blade-shaped nanoparticle has higher thermal conductivity for both MoS2 and TiO2.

Originality/value
Shape effects on Molybdenum disulphide and TiO2 nanoparticle in a microchannel with heat source is examined. The analysis of entropy shows that N(ζ)(TiO2−water) > N(ζ)(MoS2−water).
Developing a low-fluid pressure safety valve design through a numerical analysis approach
Authors: Barbaryan T. , Hoseinzadeh S. , Heyns P.S. , Barbaryan M.S. 
Published: October 2019

Purpose
This study aims to develop a new design for the fluid-safety valve to make it more environmentally friendly.

Design/methodology/approach
Computational fluid dynamics is carried out to analyse the behaviour of flow in both traditional and new safety valves.

Findings
The possibility of failure in the new design under the maximum allowable working pressure is analysed using finite element analysis.

Originality/value
Investigating a new low-fluid pressure safety valve design.