bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the relationship between high-order linkage disequilibrium and epistasis
Authors: Zan Yanjun , Forsberg Simon K. G. , Carlborg Örjan 
Published: April 2018

AbstractA plausible explanation for statistical epistasis revealed in genome wide association analyses is the presence of high order linkage disequilibrium (LD) between the genotyped markers tested for interactions and unobserved functional polymorphisms. Based on findings in experimental data, it has been suggested that high order LD might be a common explanation for statistical epistasis inferred between local polymorphisms in the same genomic region. Here, we empirically evaluate how prevalent high order LD is between local, as well as distal, polymorphisms in the genome. This could provide insights into whether we should account for this when interpreting results from genome wide scans for statistical epistasis. An extensive and strong genome wide high order LD was revealed between pairs of markers on the high density 250k SNP-chip and individual markers revealed by whole genome sequencing in the A. thaliana 1001-genomes collection. The high order LD was found to be more prevalent in smaller populations, but present also in samples including several hundred individuals. An empirical example illustrates that high order LD might be an even greater challenge in cases when the genetic architecture is more complex than the common assumption of bi-allelic loci. The example shows how significant statistical epistasis is detected for a pair of markers in high order LD with a complex multi allelic locus. Overall, our study illustrates the importance of considering also other explanations than functional genetic interactions when genome wide statistical epistasis is detected, in particular when the results are obtained in small populations of inbred individuals.
Live-cell imaging of marked chromosome regions reveals dynamics of mitotic chromosome resolution and compaction
Authors: Eykelenboom John K. , Gierliński Marek , Yue Zuojun , Hegarat Nadia , Pollard Hilary , Fukagawa Tatsuo , Hochegger Helfrid , Tanaka Tomoyuki U. 
Published: April 2018

SummaryWhen human cells enter mitosis, chromosomes undergo substantial changes in their organisation to resolve sister chromatids and compact chromosomes. Despite the fundamental importance of this phenomenon to genome stability, we still do not fully comprehend the timing and coordination of these events. To address these questions, we need to evaluate the progression of both sister chromatid resolution and chromosome compaction in one assay. We achieved this by analysing changes in configuration of marked chromosome regions over time, with high spatial and temporal resolution. This assay showed that sister chromatid resolution is an iterative process that begins in late G2 phase and completes in prophase. Cohesins and WAPL antagonistically regulate sister chromatid resolution in late G2 and prophase whilst local enrichment of cohesin on chromosomes prevents precocious sister chromatid resolution. Moreover, our assay allowed quantitative evaluation of the timing and efficiency of condensin II and I activities in promoting sister chromatid resolution and chromosome compaction, respectively. Thus, our real-time assay sheds new light on the dynamics of mitotic chromosome resolution and compaction.
A large-scale population study of early life factors influencing left-handedness
Authors: de Kovel Carolien G.F. , Carrión-Castillo Amaia , Francks Clyde 
Published: April 2018

AbstractHand preference is a conspicuous variation in human behaviour, with a worldwide proportion of around 90% of people preferring to use the right hand for many tasks, and 10% the left hand. We used the large, general population cohort of the UK biobank (~500,000 participants) to study possible relations between early life factors and adult hand preference. The probability of being left-handed was affected by the year and location of birth, likely due to cultural effects. In addition, handedness was affected by birthweight, being part of a multiple birth, season of birth, breastfeeding, and sex, with each effect remaining significant after accounting for all others. Maternal smoking showed no association with handedness. Analysis of genome-wide genotype data showed that left-handedness was very weakly heritable, but shared no genetic basis with birthweight. Although on average left-handers and right-handers differed for a number of early life factors, all together these factors had only a minimal predictive value for individual hand preference. Therefore other, unknown effects must be involved, including possible environmental factors, and/or random developmental variation with respect to the left-right formation of the embryonic brain.Significance statementLeft-right laterality is an important aspect of human brain organization which is set up early in development. Left-handedness is an overt and relatively prevalent form of atypical brain laterality. Various, often related, early life factors have been previously studied in relation to handedness, but often in small samples, or samples with biased selection schemes. Here we have performed the largest ever study of left-handedness in relation to early life factors. Left-handedness was very weakly heritable and there were significant effects of various factors such as birthweight, which remained significant after controlling for all others. However, considered all together, early life factors still had poor predictive power for the handedness of any given individual. Very early developmental perturbations, caused by environmental or chance effects in embryonic development, are therefore likely to cause left-handedness.
Prader-Willi locus Snord116 RNA processing requires an active endogenous allele and neuron-specific splicing by Rbfox3/NeuN
Authors: Coulson Rochelle L. , Powell Weston T. , Yasui Dag H. , Dileep Gayathri , Resnick James , LaSalle Janine M. 
Published: April 2018

AbstractPrader-Willi syndrome (PWS), an imprinted neurodevelopmental disorder characterized by metabolic, sleep, and neuropsychiatric features, is caused by the loss of paternal SNORD116, containing only noncoding RNAs. The primary SNORD116 transcript is processed into small nucleolar RNAs (snoRNAs), which localize to nucleoli, and their spliced host gene 116HG, which is retained at its site of transcription. While functional complementation of the SNORD116 noncoding RNAs is a desirable goal for treating PWS, the mechanistic requirements of SNORD116 RNA processing are poorly understood. Here we developed and tested a novel transgenic mouse which ubiquitously expresses Snord116 on both a wild-type and Snord116 paternal deletion (Snord116+/−) background. Interestingly, while the Snord116 transgene was ubiquitously expressed in multiple tissues, splicing of the transgene and production of snoRNAs was limited to brain tissues. Knockdown of Rbfox3, encoding neuron-specific splicing factor NeuN, in Snord116+/−-derived neurons reduced splicing of the transgene in neurons. RNA fluorescent in situ hybridization for 116HG revealed a single significantly larger signal in transgenic mice, demonstrating colocalization of transgenic and endogenous 116HG RNAs. Similarly, significantly increased snoRNA levels were detected in transgenic neuronal nucleoli, indicating that transgenic Snord116 snoRNAs were effectively processed and localized. In contrast, neither transgenic 116HG nor snoRNAs were detectable in either non-neuronal tissues or Snord116+/− neurons. Together, these results demonstrate that exogenous expression and neuron-specific splicing of the Snord116 locus are insufficient to rescue the genetic deficiency of Snord116 paternal deletion. Elucidating the mechanisms regulating Snord116 processing and localization are essential to develop effective gene replacement therapies for PWS.
Whole Exome Sequencing in 20,197 Persons for Rare Variants in Alzheimer Disease
Authors: Raghavan Neha S. , Brickman Adam M. , Andrews Howard , Manly Jennifer J. , Schupf Nicole , Lantigua Rafael ,   The Alzheimer’s Disease Sequencing Project, Wolock Charles J. , Kamalakaran Sitharthan , Petrovski Slave , Tosto Giuseppe , Vardarajan Badri N. , Goldstein David B. , Mayeux Richard 
Published: April 2018

AbstractObjectiveThe genetic bases of Alzheimer’s disease remain uncertain. An international effort to fully articulate genetic risks and protective factors is underway with the hope of identifying potential therapeutic targets and preventive strategies. The goal here was to identify and characterize the frequency and impact of rare and ultra-rare variants in Alzheimer’s disease using whole exome sequencing in 20,197 individuals.MethodsWe used a gene-based collapsing analysis of loss-of-function ultra-rare variants in a case-control study design with data from the Washington Heights-Inwood Columbia Aging Project, the Alzheimer’s Disease Sequencing Project and unrelated individuals from the Institute of Genomic Medicine at Columbia University.ResultsWe identified 19 cases carrying extremely rare SORL1 loss-of-function variants among a collection of 6,965 cases and a single loss-of-function variant among 13,252 controls (p = 2.17 × 10-8; OR 36.2 [95%CI 5.8 – 1493.0]). Age-at-onset was seven years earlier for patients with SORL1 qualifying variant compared with non-carriers. No other gene attained a study-wide level of statistical significance, but multiple top-ranked genes, including GRID2IP, WDR76 and GRN, were among candidates for follow-up studies.InterpretationThis study implicates ultra-rare, loss-of-function variants in SORL1 as a significant genetic risk factor for Alzheimer’s disease and provides a comprehensive dataset comparing the burden of rare variation in nearly all human genes in Alzheimer’s disease cases and controls. This is the first investigation to establish a genome-wide statistically significant association between multiple extremely rare loss-of-function variants in SORL1 and Alzheimer’s disease in a large whole-exome study of unrelated cases and controls.
Information asymmetry and financial dollarization in sub-Saharan Africa
Authors: Asongu Simplice , Raheem Ibrahim , Tchamyou Venessa 
Published: April 2018

Purpose
Financial dollarisation in sub-Saharan Africa (SSA) is most persistent compared to other regions of the world. The purpose of this paper is to complement the existing scant literature on dollarisation in Africa by assessing the role of information sharing offices (public credit registries and private credit bureaus) on financial dollarisation in 25 SSA countries for the period 2001-2012.

Design/methodology/approach
The empirical evidence is based on ordinary least squares and generalised method of moments (GMM).

Findings
The findings show that information sharing offices (which are designed to reduce information asymmetry) in the banking industry are a deterrent to dollarisation. The underpinning assumption that financial development reduces financial dollarisation is confirmed.

Originality/value
There is scant literature on the relevance of information sharing offices in development outcomes in Africa. While the establishment of these offices in most countries in the continent began in 2004, scholarship on the importance of these offices in financial development is sparse.
Exploitation versus exploration
Authors: Zhao Haiyuan , Peng Xiaobao 
Published: April 2018

PurposeThis paper aims to draw on the network perspective of organizational innovation to present an argument on how a subsidiary should select innovation behavior.Design/methodology/approachIn this framework, the paper analyzes middle- and high-level managers of subsidiaries from various industries located in the Chinese Mainland.FindingsThe results suggest the following ideas: internal embeddedness is positively related to exploitation innovation, external embeddedness is inverted-U related to exploration innovation, the availability of alternatives positively moderates the main effects, whereas restraint in the use of power negatively moderates them.Research limitations/implicationsThe current study has a few limitations that provide meaningful research directions for future investigations. First, it only considers the industry and ownership as control variables. Second, this study was conducted in the Chinese context.Practical implicationsThe analysis of the relationship between embeddedness and innovation behavior also shows that focal subsidiary must dynamically adjust the way of embeddedness on the basis of its strategy, and it can reasonable leverage strategic assets for exploitation innovation or exploration innovation. From the perspective of headquarters, establishing deep embeddedness with a subsidiary and giving it indispensable support are important to promote that subsidiary’s exploitation innovation.Social implicationsThe focal subsidiary should establish relationships with more alternative partners and develop relationships with power-advantaged partners through strategies such as a long-term contract, establishing an R&D alliance and entering a joint venture. Besides this, more powerful partners in the internal network should adopt various power usage strategies to promote focal subsidiary exploitation innovation and more powerful partners in the external network should show restraint in the use of power toward any subsidiary in an over-embedded situation. The result shows environment dynamism affects subsidiary exploration innovation more deeply than exploitation innovation. Consequently, managers should recognize the importance of dynamic adaptation to environmental changes and adjust their firms’ innovation behavior accordingly, especially when they are implementing an exploration innovation strategy.Originality/valueThe extent of embeddedness in an innovation network shapes the subsidiary innovation behavior, and this effect is moderated by power. The focal subsidiary should dynamically and strategically adjust its innovation behavior considering various its type and level of embeddedness.
Elaborations on the role of project owner: introducing project owners type 1 and 2
Authors: Olsson Nils O.E. 
Published: April 2018

Purpose
The purpose of this paper is to study how the project owner role is described in the literature, and how the role is carried out in practice. In particular, the author studies the project owner role in relation to project execution and benefit realization.

Design/methodology/approach
Based on a literature review, the author proposes a model for the relationships between the project owner, project manager and the operation of project delivery. The author then uses the model to describe the empirical results derived from a mapping of project owner responsibilities in a set of Norwegian information technology projects.

Findings
The author defines a project owner type 1 as a project owner that is focused on the business case and has responsibility for both project delivery and benefit realization. This project owner is the type described in most of the literature. The author further defines a project owner type 2 as a project owner that is mainly concerned with supporting the project manager and enabling project delivery. This is the type of project owner found in the empirical study.

Research limitations/implications
The author identified a mismatch between the project management literature and observed practice.

Practical implications
There is a need to clarify the type of project owner role referred to in different contexts. Different project owners will have a different set of incentives and priorities. It is important to make sure that both investment costs and benefits (i.e., the complete business case), are seen in close relation to each other and not as separate undertakings.

Originality/value
There is a need for a distinction between two types of project owners. This study proposes a framework for the description, analysis and implementation of project governance, with a special focus on the project owner role.
Waste management in a wire and cable company through system dynamics approach
Authors: Saryazdi Ali Haji Gholam , Ghavidel Mohammad 
Published: April 2018

Purpose
The purpose of this paper is to investigate the dynamics of waste production in the product structure of a wire and cable manufacturing company that deals with a high-volume waste and proposes strategies that reduce product costs.

Design/methodology/approach
The methodology for this research is descriptive and expressive modeling in a way that theories of research have been extracted from literature and field studies have been done based on the company specialists’ views. The system dynamics has been used to analyze and model waste in a wire and cable firm.

Findings
Applying SD approach in the paper not only helps to identify the structure of producing the waste, which is complicated and dynamic, but also proposes ways to reduce them and illustrate the applied results. The second outcome shows that in the waste management there should be a digression in a managerial view to the systematic thought. In the other word as in the system dynamic approach, the expansion of the model boundary is one of the objectives to find appropriate solution. The behavior model showed that in the waste management the most effective way to reduce the waste is to buy qualified raw material which is out of the firm.

Originality/value
This paper not only shows that the system dynamic approach is appropriate for the waste management problems which are complicated and dynamic but also proved that in the waste management system the solutions are not always near or within the firm. They should be identified by a systematic approach.
Integrated approach for evaluation of service quality in multistage sequential utilitarian service process
Authors: Roy Sheila , Mukherjee Indrajit 
Published: April 2018

Purpose
In the context of sequential multistage utilitarian service processes, the purpose of this study is to develop and validate propositions to study the impact of service quality (SQ) perceptions developed in intermediate stages, along with the impact of service gestalt characteristics, such as peak and end experiences, on quality perception at each stage and on overall service quality (OSQ) perception. The cascade phenomenon (interdependency between process stages) is considered in the evaluation of OSQ perception of customer, who experiences service through a series of planned, distinct and partitioned sequential stages.

Design/methodology/approach
In this paper, a conceptual framework is used to evolve the propositions. Subsequently, propositions are tested in three different utilitarian service contexts wherein customer survey was conducted for feedback on attributes at each stage, summary perception evaluations of each stage and OSQ evaluation of multistage process. Peak experiences, considered for OSQ evaluation, were defined by a suitable statistical technique. Ordinal logistic regression with nested models is the technique used for analyzing the data.

Findings
This work reveals significant cascade effect of summary evaluation of intermediate stages on the subsequent stage. Peak customer experience (negative or positive) is observed to be marginally significant on intermediate stage and OSQ evaluation. In addition, OSQ is observed to be influenced by summary perception evaluations of intermediate stages, which leads to better model adequacy. Finally, among all the stages, end stage performance is observed to have a significant impact on the overall multistage SQ.

Practical implications
The findings suggest that in view of the cascade effect of intermediate stages, managers need to allocate resources to ensure that all stages are performing at an adequate level instead of only focusing on improving peaks and end effects of customer experiences. The proposed approach is easy to implement and suitable for evaluating SQ and OSQ in varied multistage sequential utilitarian service environment.

Originality/value
An integrated approach for evaluation of SQ in sequential multistage utilitarian service processes is proposed from the perspective of cascade effect of intermediate stages and peak and end effects on OSQ perception.
Exploring the experiences of trainee mental health workers: moving from theory to practice
Authors: Kirton Charlotte , Lambert Nicky , Matheson Helen , Connell Sandra 
Published: April 2018

Purpose
The Trainee Mental Health Worker (TMHW) Programme is an initiative developed collaboratively between Middlesex University and local NHS Mental Health Trusts in response to national workforce requirements for flexible clinical personnel. The purpose of this paper is to explore the experience of this new category of mental health workers and to address the feedback given by previous cohorts of TMHWs.

Design/methodology/approach
This qualitative study comprised of three focus groups who met over their year-long training. In total, 20 participants self-selected from a population of 60 TMHWs, and their expectations of the TMHW role prior to starting the programme and following each of two practice placements were explored.

Findings
The thematic analysis identified five domains: identity, career strategy, functioning in the system, status and responsibility; the TMHWs demonstrated notable changes in their attitude and behaviour as they progressed. The findings demonstrate the challenges of integrating a new type of workforce into the rigid systems of the health care service.

Research limitations/implications
Focus groups by their nature are not always representative, and this programme is limited in its number of students.

Practical implications
This study has led to a greater understanding of the experiences of trainees across a variety of clinical settings.

Social implications
The results from this study will assist employing trusts in recruitment and retention by helping them to understand this phenomenon and the role itself.

Originality/value
This study’s value lies in the insight it offers into the experience of a new kind of worker moving from novice status to practitioner outside the constraint of a professional registration.
Conceptualizing negatively valenced influencing behavior: forms and triggers
Authors: Azer Jaylan , Alexander Matthew J. 
Published: April 2018

Purpose
The purpose of this paper is to show how customers engage in negatively valenced influencing behavior (NVIB) and what triggers customers to use different forms of NVIB in an online context.

Design/methodology/approach
A qualitative study is conducted using an unobtrusive netnography. Data collected comprise of 954 negatively valenced online reviews posted on TripAdvisor to hotels, restaurants, and “things to do” in 12 different destinations worldwide.

Findings
Drawing on the recent literature relating to customer engagement behavior (CEB), this paper identifies and conceptualizes the relationship between five cognitive (service failure, overpricing, deception) and emotional (disappointment and insecurity) triggers of six forms of direct (dissuading, warning, and endorsing competitors) and indirect (discrediting, expressing regret, and deriding) NVIB.

Research limitations/implications
The unobtrusive netnography has inherent limitations that lend itself to inductive rich insights rather than generalization. The study only focuses on NVIB within a specific online context, namely, TripAdvisor.

Practical implications
This paper provides managers with knowledge of the specific triggers of NVIB. Additionally, the paper conceptualizes the various forms of NVIB, how customers use them, and what triggers them to use each form. Moreover, the paper offers relevant data-inferred recommendations to service managers on how to manage each form of NVIB.

Originality/value
This research is the first to identify the forms and triggers of NVIB, classify direct and indirect forms, and conceptualize the relationships between forms and triggers.