bluuebunny/crossref_metadata_2025_split huggingface dataset:
The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension
Authors: Keskin Isil , Forsgren Elin , Lehmann Manuela , Andersen Peter M. , Brännström Thomas , Lange Dale J. , Synofzik Matthis , Nordström Ulrika , Zetterström Per , Marklund Stefan L. , Gilthorpe Jonathan D. 
Published: May 2018

AbstractMutations that destabilize superoxide dismutase 1 (SOD1) are a cause of amyotrophic lateral sclerosis (ALS). SOD1, which is located in the reducing cytosol, contains an oxidized disulfide bond required for stability. We show that the bond is an Achilles heel of the protein because it is sensitive to the oxygen tension. Culture of ALS patient-derived fibroblasts, astrocytes and induced pluripotent stem cell-derived mixed motor neuron and astrocyte cultures (MNACs) under lowered oxygen tensions caused reductive bond cleavage and misfolding. The effects were greatest in cells expressing mutant SOD1s, but also occurred in wild type SOD1 in cultures derived from patients carrying ALS-linked mutations inC9orf72, FUSandTBK1, as well as from controls. MNACs showed a greater response than the other cell types, including enhanced SOD1 aggregation, in line with the vulnerability of the motor system. Our results show that oxygen tension is a principal determinant of SOD1 stability and shed light on how risk factors for ALS, such as aging and other conditions causing reduced vascular perfusion, could lead to disease initiation and progression.Subject categoriesNeuroscience; Molecular Biology of Disease
Floating search methodology for combining classification models for site recognition in DNA sequences
Authors: Pérez-Rodríguez Javier , de Haro-García Aida , García-Pedrajas Nicolás 
Published: May 2018

AbstractRecognition of the functional sites of genes, such as translation initiation sites, donor and acceptor splice sites and stop codons, is a relevant part of many current problems in bioinformatics. Recognition of the functional sites of genes is also a fundamental step in gene structure predictions in the most powerful programs. The best approaches to this type of recognition use sophisticated classifiers, such as support vector machines. However, with the rapid accumulation of sequence data, methods for combining many sources of evidence are necessary as it is unlikely that a single classifier can solve this type of problem with the best possible performance.A major issue is that the number of possible models to combine is large and the use of all of these models is impractical. In this paper, we present a framework that is based on floating search for combining as many classifiers as needed for the recognition of any functional sites of a gene. The methodology can be used for the recognition of translation initiation sites, donor and acceptor splice sites and stop codons. Furthermore, we can combine any number of classifiers that are trained on any species. The method is also scalable to large datasets, as is shown in experiments in which the whole human genome is used. The method is also applicable to other recognition tasks.We present experiments on the recognition of these four functional sites in the human genome, which is used as the target genome, and use another 20 species as sources of evidence. The proposed methodology shows significant improvement over state-of-the-art methods for use in a thorough evaluation process. The proposed method is also able to improve heuristic selection of species to be used as sources of evidence as the search finds the most useful datasets.Author summaryIn this paper we present a methodology for combining many sources of information to recognize some of the most important functional sites in a genomic sequence. The functional sites of the sequences, such as, translation start sites, translation initiation sites, acceptor and donor splice sites and stop codons, play a very relevant role in many Bioinformatics tasks. Their accurate recognition is an important task by itself and also as part of gene structure prediction programs.Our approach uses a methodology usually termed in Computer Science as “floating search”. This is a powerful heuristics applicable when the cost of evaluating each possible solution is high. The methodology is applied to the recognition of four different functional sites in the human genome using as additional sources of evidence the annotated genomes of other twenty different species.The results show an advantage of the proposed method and also challenge the standard assumption of using only genomes not very close and not very far from the human to improve the recognition of functional sites in the human genome.
The interplay between small RNA pathways shapes chromatin landscapes inC. elegans
Authors: Gushchanskaia Ekaterina , Esse Ruben , Ma Qicheng , Lau Nelson , Grishok Alla 
Published: May 2018

ABSTRACTThe nematodeC. eleganscontains several types of endogenous small interfering RNAs (endo-siRNAs) produced by RNA-dependent RNA polymerase (RdRP) complexes. Both “silencing” siRNAs bound by Worm-specific Argonautes (WAGO) and “activating” siRNAs bound by the CSR-1 Argonaute require the DRH-3 helicase, an RdRP component. Here we show that, in thedrh-3(ne4253)mutant deficient in RdRP-produced secondary endo-siRNAs, the silencing histone mark H3K9me3 is largely depleted, whereas in thecsr-1partial loss-of-function mutant this mark is ectopically deposited on CSR-1 target genes. Moreover, we observe ectopic H3K9me3 at enhancer elements in bothdrh-3andcsr-1partial loss-of-function mutants and describe small RNAs matching enhancers. Finally, we detect accumulation of H3K27me3 at highly expressed genes in thedrh-3(ne4253)mutant, which correlates with their reduced transcription. Our study shows that when abundant RdRP-produced siRNAs are depleted, there is ectopic elevation of noncoding RNAs linked to increase in silencing chromatin marks. Moreover, our results suggest that enhancer small RNAs may guide local H3K9 methylation.
3D protein structure from genetic epistasis experiments
Authors: Rollins Nathan J. , Brock Kelly P. , Poelwijk Frank J. , Stiffler Michael A. , Gauthier Nicholas P. , Sander Chris , Marks Debora S. 
Published: May 2018

SummaryHigh-throughput experimental techniques have made possible the systematic sampling of the single mutation landscape for many proteins, defined as the change in protein fitness as the result of point mutation sequence changes. In a more limited number of cases, and for small proteins only, we also have nearly full coverage of all possible double mutants. By comparing the phenotypic effect of two simultaneous mutations with that of the individual amino acid changes, we can evaluate epistatic effects that reflect non-additive cooperative processes. The observation that epistatic residue pairs often are in contact in the 3D structure led to the hypothesis that a systematic epistatic screen contains sufficient information to identify the 3D fold of a protein. To test this hypothesis, we examined experimental double mutants for evidence of epistasis and identified residue contacts at 86% accuracy, including secondary structure elements and evidence for an alternative all-α-helical conformation. Positively epistatic contacts – corresponding to compensatory mutations, restoring fitness – were the most informative. Folded models generated from top-ranked epistatic pairs, when compared with the known structure, were accurate within 2.4 Å over 53 residues, indicating the possibility that 3D protein folds can be determined experimentally with good accuracy from functional assays of mutant libraries, at least for small proteins. These results suggest a new experimental approach for determining protein structure.
The corrosion resistance of low concentration ruthenium laser alloyed 304L stainless steel exposed to sulphuric acid at 25°C
Authors: Van der Merwe Josias Willem , Nelwalani Ndivhuwo Brayner 
Published: May 2018

PurposeThis paper aims to study the effect of small ruthenium additions through laser surface alloying of 304L stainless steel on the corrosion resistance when exposed to a 1 M sulphuric acid solution at 25°C.Design/methodology/approachIn this study, the characteristics of laser-alloyed surface layers enriched with low concentrations of ruthenium, less than 0.3 Wt.%, were evaluated. Samples were manufactured by performing laser surface alloying on a 304L stainless steel and using a 304 stainless steel powder enriched with ruthenium. The welded surfaces were cross-sectioned and the microstructure and chemical composition were analysed; in addition, the depth of penetration was determined. The corrosion characteristics of these surface welds were investigated through electrochemical analysis such as open circuit potential measurements and potentiodynamic scans.FindingsIt was found that with the addition of ruthenium levels of more than 0.2 Wt.%, the corrosion characteristics when exposed to 1 M sulphuric acid improved in the enriched welded zone.Research limitations/implicationsThis study investigated the improvement of the surface layer of the 304L stainless steel because of the cost involved when ruthenium is alloyed in the bulk and showed that an improved corrosion resistance can be achieved in sulphuric acid at room temperature.Practical implicationsThe hardness of the laser alloying was not significantly affected by the ruthenium, but more by the laser parameters.Originality/valueThis paper considers the improvement of 304L stainless steel through laser alloying with ruthenium.
A systemic exploration of drivers for and constraints on construction productivity enhancement
Authors: Javed Arshad Ali , Pan Wei , Chen Le , Zhan Wenting 
Published: May 2018

Purpose
The purpose of this paper is to investigate the complex interdependence of the factors in driving or hindering construction productivity at the industry, project and activity levels in a systemic manner.

Design/methodology/approach
A mixed-methods design, which combines a critical literature review, an interview-based survey with 32 industry experts and five focus group meetings participated in by 109 representatives of a wide range of industry stakeholder groups, was employed to identify the drivers for and constraints on construction productivity enhancement in Hong Kong and explore the interrelated insights into the drivers and constraints.

Findings
The study conceptualised and validated a systemic framework for examining construction industry productivity, and developed three causal loop diagrams (CLDs) for illustrating the dynamic structures that underpin the complex systems of the drivers and constraints.

Research limitations/implications
Although the scope of the study was limited to Hong Kong, the results could be interpreted for critical learning in other urban contexts.

Practical implications
The systemic perspective of construction productivity and the CLDs of the drivers and constraints support the systems thinking of industry stakeholders in the formulation of holistic strategies for long-term construction industry productivity enhancement.

Originality/value
The study conceptualises construction productivity from a systemic perspective and provides empirically supported CLDs to facilitate future investigations into the complex system of construction productivity.
Improving contractor social networking on IBS infrastructure maintenance projects: a review
Authors: Ismail Zul-Atfi Bin 
Published: May 2018

Purpose
A key factor adversely affecting contractor social networking performance is the improper handling and information management of contractor’s services delivery on websites. Contractor social networking is particularly problematic on industrialised building system (IBS) infrastructure maintenance projects where contractor’s certified quality product and firms are not matched with maintenance specialisation services. The paper aims to discuss this issue.

Design/methodology/approach
This paper reports on the early stages of research which is developing a new information and communications technology (ICT)-based approach to managing contractor social networking on IBS infrastructure maintenance schemes. As a precursor to this work, the paper reviews current contractor social networking websites practices on IBS infrastructure maintenance projects and explores the ICT tools and techniques currently being employed on such projects.

Findings
The findings reveal the need for more sophisticated contractor social networking websites solutions which accord with the needs of IBS infrastructure maintenance schemes.

Originality/value
The paper concludes by presenting a research framework for developing such a system in the future.
Gender-segregated labour spaces and social capital – does context matter?
Authors: Sheerin Corina , Hughes Caitriona 
Published: May 2018

Purpose
This research aims to explore the role of social capital and specifically networks in role, and career development for women within two very distinct gender-segregated contexts of the labour market, namely, investment management and human resource management (HRM).

Design/methodology/approach
This research is qualitative in nature, underpinned by an interpretivist philosophical stance. Thematic analysis is used to analyse the findings from 32 in-depth interviews with HR and investment management managers.

Findings
The findings advance our understanding of social capital and its development as a social process, which differs according to labour market contexts. The results indicate divergence among participants regarding how they access networks as well as the perceived role and benefits of networking and social capital accumulation in their career and personal development.

Practical implications
For human resource development (HRD) practitioners, there are implications in relation to the need to tailor development and support structures cognisant of the occupational context. Specifically, the findings of this study indicate the acute need to support network access for those “outsider” women in male-dominated spaces. A need to enhance awareness of the benefits of networks to both organisations and employees across the labour market is warranted. For organisations, networks underlie social capital accumulation, which in turn increases efficiency and generates business solutions. For the employee, networks are an important self-development and career advancement tool. Such connections need to be supported and developed. Within patriarchal spaces particularly, HRD professionals need to provide support to women in extending their networks both within and outside the organisation.

Originality/value
This research makes an essential contribution to the literature by examining the influence of context in the development of social capital within two polarized labour market locations. The findings highlight the difficulties women face when developing social capital in investment management in contrast to the relative ease, which HRM professionals experience. Such findings also bring to light the essential role of HRD professionals as advocates for change in such contexts.
Perceptions of customer service orientation, training, and employee engagement in Jamaica’s hospitality sector
Authors: Johnson Karen R. , Park Sunyoung , Bartlett Kenneth R. 
Published: May 2018

PurposeThe purpose of this study is to examine the relationship between service orientation, customer service training and employee engagement of firms in the hospitality sector of the tourism industry.Design/methodology/approachA total of 231 responses from 13 large all-inclusive hotels in Jamaica are analyzed by using structural equation modeling.FindingsOverall, service orientation positively affected customer service training and employee engagement. In addition, customer service training positively affected employee engagement. Furthermore, the results indicate that customer service training mediates the relationship between service orientation and employee engagement.Research limitations/implicationsThis study builds on the conceptual literature of engagement and adds to the limited empirical studies to date to highlight the importance of service-oriented culture and training activities on employee engagement.Practical implicationsThe findings of the study generate an increased understanding of the importance of an engaged workforce and of specific customer service training practices that can foster engagement. This study also highlights that managers should be supportive of training and development activities within a broader context that considers specific desired workplace performance from employees.Originality/valueThe knowledge gap related to many frequently used organizational practices reported as having an impact on engagement is addressed. Addressing this problem extends existing literature and provides an evidence base for human resource managers and professionals in service organizations, specifically in hospitality firms.
“I’m not in the truth business”: the politics of climate change with pre-service teachers
Authors: Damico James S. , Panos Alexandra , Baildon Mark 
Published: May 2018

PurposeThis study was designed to be an agonistic encounter between two pre-service teachers from different academic disciplines and with opposing climate change beliefs. The purpose of this study was to create an opportunity for this pair of future educators to voice, acknowledge and engage their differences, rather than avoid or skirt them.Design/methodology/approachUsing a paired interview approach, two pre-service teachers discussed online sources about climate change. The analysis focuses on critical literacy practices of textual critique and reader reflexivity, considering how students from different beliefs and perspectives engage in agonism and negotiated practices.FindingsWhile there was evidence of the two students engaged in critical literacy practices of textual critique, most of this engagement with the sources remained more at a surface level with somewhat superficial criteria to evaluate the sources. The two students engaged reflexively during the interview discussion in terms of their academic disciplines and climate change beliefs. This reflexive work produced the most compelling exchanges during the interview discussion and pointed to two rich sites for agonistic engagement: their differing conceptions of reliability and their competing perspectives about the intersection of science and politics.Originality/valueAgonism offers a lens that helps ensure we understand that all pursuits toward facts and truth are necessarily contested as we engage with respected adversaries, not enemies we need to vanquish. There is an urgent need for dialogue across difference, especially for people in the increasingly polarized USA with complex topics and challenges such as climate change.
Effects of asymmetric information on market timing in the mutual fund industry
Authors: Tchamyou Venessa S. , Asongu Simplice A. , C. Nwachukwu Jacinta 
Published: May 2018

Purpose
The purpose of this paper is to investigate the effects of information asymmetry (between the realized return and the expected return) on market timing in the mutual fund industry.

Design/methodology/approach
For the purpose, the authors use a panel of 1,488 active open-end mutual funds for the period 2004-2013. The authors use fund-specific time-dynamic betas. The information asymmetry is measured as the standard deviation of idiosyncratic risk. The data set is decomposed into five market fundamentals in order to emphasis the policy implications of the findings with respect to: equity, fixed income, allocation, alternative, and tax-preferred mutual funds. The empirical evidence is based on endogeneity-robust difference and system generalized method of moments.

Findings
The following findings are established. First, the information asymmetry broadly follows the same trend as volatility, with a higher sensitivity to market risk exposure. Second, fund managers tend to raise (cutback) their risk exposure in time of high (low) market liquidity. Third, there is evidence of convergence in equity funds. The authors may, therefore, infer that equity funds with lower market risk exposure are catching-up with their counterparts with higher exposure to fluctuation in market conditions.

Originality/value
The paper complements the sparse literature on market timing in the mutual fund industry with time-dynamic betas, information asymmetry and an endogeneity-robust empirical approach.
Surfing or flowing? How to retain e-customers on the internet
Authors: Herrando Carolina , Jimenez-Martinez Julio , Martin de Hoyos M. Jose 
Published: May 2018

Purpose
Social commerce websites entail a completely new scenario for retaining e-customers due to the richness of their social interactions. Nowadays, users can interact with companies and with other users; hence, it is considered important to study how social stimuli affect users. Drawing on the Stimulus Organism Response framework and Flow Theory, this paper aims to propose that the social stimulus (sPassion) has a positive effect on the organism (state of flow) causing positive responses from users (flow consciousness, trust and eLoyalty).

Design/methodology/approach
The data were collected through an online survey. The sample consists of 771 users of social commerce websites, of which 51 per cent are male and 49 per cent female, aged between 16 and 80 years. The structural equation model statistical software EQS 6 was used to test the model.

Findings
The empirical results confirm that passionate users are prone to experience state of flow, and, as a consequence, they are conscious of this optimal experience, resulting in an increase in trust.

Originality/value
The originality of this research stems from analysing how users’ passion on social commerce creates an optimal experience that boost customers’ retention.
Betting exclusively by private labels: could it have negative consequences for retailers?
Authors: Ruiz-Real José Luis , Gázquez-Abad Juan Carlos , Esteban-Millat Irene , Martínez-López Francisco J. 
Published: May 2018

PurposeThe authors analyze the relationship between different consumer attitudinal variables and a number of variables related to consumer perception of the store and purchasing behavior, in assortments composed exclusively of private labels (PLs).Design/methodology/approachThe authors developed an experiment based on an online survey to test the hypotheses formulated. The model’s causal relationships are established using structural equations.FindingsThe image of stores that only offer their own brand is mainly configured by price consciousness and the attitude toward the private label. The private label purchase intention is strongly influenced by the store image and a favorable attitude toward the brand, and loyalty strategies should be aimed at securing a clear perception of providing real value.Practical implicationsFor retailers who only offer their own brands, an assortment with price-competitive PLs is key to the strategy of differentiating them from other retailers. It is reasonable to assume that, if retailers have a favorable image, customers transfer this brand value to their PLs and trust them. Customer loyalty strategies of these retailers should be aimed at ensuring that consumers clearly perceive that their assortment provides real value and that, although it is limited in terms of number of brands, it can meet all their needs.Originality/valueThis research represents a significant contribution to brand management literature because, includes, together with loyalty to the store, its image and the PL purchase intention as consumer response variables. Another differentiating feature is the methodology used. Estimation of the structural equation model permits the simultaneous estimation of the relationships between the variables.