bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ximmer: A System for Improving Accuracy and Consistency of CNV Calling from Exome Data
Authors: Sadedin Simon P , Ellis Justine A , Masters Seth L , Oshlack Alicia 
Published: February 2018

AbstractDetection of copy number variation (CNVs) is a challenging but highly valuable application of exome and targeted high throughput sequencing (HTS) data. While there are dozens of CNV detection methods available, using these methods remains challenging due to variable accuracy both across different data sets and within the same data set with different methods. We propose that extracting good results from CNV detection on HTS data requires a systematic approach involving rigorous quality control, adjustment of method parameters and calibration of confidence measures for filtering results. We present Ximmer, a tool which supports an end to end process for applying these procedures including a simulation framework, CNV detection analysis pipeline, and a visualisation and curation tool which enables interactive exploration of CNV results. We apply Ximmer to perform a comprehensive evaluation of CNV detection on four data sets using four different detection methods, representing one of the most comprehensive evaluations to date. Ximmer is open source and freely available at http://ximmer.org (example results are viewable at http://example.ximmer.org).
Non-invasive Assessment of Liver Disease in Rats Using Multiparametric Magnetic Resonance Imaging: A Feasibility Study
Authors: Hoy Anna M. , McDonald Natasha , Lennen Ross J. , Milanesi Matteo , Herlihy Amy H. , Kendall Timothy J. , Mungall William , Gyngell Michael , Banerjee Rajarshi , Janiczek Robert L. , Murphy Philip S. , Jansen Maurits A. , Fallowfield Jonathan A. 
Published: February 2018

AbstractBackground & AimsNon-invasive quantitation of chronic liver disease using multiparametric MRI has the potential to refine clinical care pathways, trial design and preclinical drug development. The aim of the study was to evaluate the use of multiparametric liver MRI in experimental rat models of chronic liver disease.Methods: Liver injury was induced in male wild-type Sprague-Dawley rats using 4 or 12 weeks carbon tetrachloride (CCl4) intoxication and 4 or 8 weeks methionine and choline deficient (MCD) diet. Liver MRI was performed using a 7.0 Tesla small animal scanner at baseline and specified timepoints after liver injury. Multiparametric liver MRI parameters (T1 mapping, T2* mapping and proton density fat fraction (PDFF)) were correlated with gold standard histopathological measures, assessed by a blinded expert adjudicator. One-way analysis of variance with Tukey’s post-hoc test was used to assess differences between groups and Spearman’s rank-order correlation to examine associations.ResultsMean hepatic T1 increased significantly in rats treated with CCl4for 12 weeks compared to controls (1122±78 ms vs. 959±114 ms; d=162.7, 95% CI (11.92, 313.4),P=0.038) and correlated strongly with histological collagen content (rs=0.717,P=0.037). In MCD diet-treated rats, hepatic PDFF correlated strongly with histological fat content (rs=0.819,P<0.0001), steatosis grade (rs=0.850,P<0.0001) and steatohepatitis score (rs=0.818,P<0.0001). Although there was minimal histological iron, progressive fat accumulation in MCD diet-treated liver significantly shortened T2*.ConclusionsIn preclinical models, quantitative MRI markers correlated with histopathological assessments, especially for fatty liver disease. Validation in longitudinal studies is required.Key pointsNon-invasive quantitative measures of chronic liver injury are needed for stratification and monitoring of disease in clinical practice and in drug developmentWe adapted and applied a clinically-relevant non-contrast multiparametric MRI protocol in well-established preclinical liver disease models, for simultaneous quantitation of hepatic fat, fibro-inflammatory injury and ironMultiparametric liver MRI was feasible at 7.0 Tesla in experimental rat models and imaging parameters correlated with gold standard histopathological assessments, especially characteristics of fatty liver diseaseFurther development of multiparametric liver MRI could refine drug development strategies and impact upon trial design and clinical care pathways
Mammalian Cells Engineered to Produce Novel Steroids
Authors: Spady Emma S. , Wyche Thomas P. , Rollins Nathanael J. , Clardy Jon , Way Jeffrey C. , Silver Pamela A. 
Published: February 2018

AbstractSteroids can be difficult to modify via traditional organic synthesis methods, but many enzymes regio- and stereo-selectively process a wide variety of steroid substrates. We tested whether steroid-modifying enzymes could make novel steroids from non-native substrates. Numerous genes encoding steroid-modifying enzymes, including some bacterial enzymes, were expressed in mammalian cells by transient transfection and found to be active. We made three unusual steroids by expression in HEK293 cells of the 7α-hydroxylase CYP7B1, which was selected because of high native product yield. These cells made 7α,17α-dihydroxypregnenolone and 7β,17α-dihydroxypregnenolone from 17α-hydroxypregnenolone, and produced 11α,16α-dihydroxyprogesterone from 16α-hydroxyprogesterone. The latter two products resulted from previously unobserved CYP7B1 hydroxylation sites. A Rosetta docking model of CYP7B1 suggested that these substrates’ D-ring hydroxylations may prevent them from binding in the same way as the native substrate, bringing different carbons near the active ferryl oxygen. This new approach could use other enzymes and substrates to produce many novel steroids for drug candidate testing.
Regulation of cyclic electron flow by chloroplast NADPH-dependent thioredoxin system
Authors: Nikkanen Lauri , Toivola Jouni , Trotta Andrea , Guinea Diaz Manuel , Tikkanen Mikko , Aro Eva-Mari , Rintamäki Eevi 
Published: February 2018

ABSTRACTLinear electron transport in the thylakoid membrane drives both photosynthetic NADPH and ATP production, while cyclic electron flow (CEF) around photosystem I only promotes the translocation of protons from stroma to thylakoid lumen. The chloroplast NADH-dehydrogenase-like complex (NDH) participates in one CEF route transferring electrons from ferredoxin back to the plastoquinone pool with concomitant proton pumping to the lumen. CEF has been proposed to balance the ratio of ATP/NADPH production and to control the redox poise particularly in fluctuating light conditions, but the mechanisms regulating the NDH complex remain unknown. We have investigated potential regulation of the CEF pathways by the chloroplast NADPH-thioredoxin reductase (NTRC)in vivoby using an Arabidopsis knockout line ofNTRCas well as lines overexpressing NTRC. Here we present biochemical and biophysical evidence showing that NTRC activates the NDH-dependent CEF and regulates the generation of proton motive force, thylakoid conductivity to protons and redox balance between the thylakoid electron transfer chain and the stroma during changes in light conditions. Further, protein–protein interaction assays suggest a putative thioredoxin-target site in close proximity to the ferredoxin binding domain of NDH, thus providing a plausible mechanism for regulation of the NDH ferredoxin:plastoquinone oxidoreductase activity by NTRC.One sentence summaryChloroplast thioredoxins regulate photosynthetic cyclic electron flow that balances the activities of light and carbon fixation reactions and improves plant fitness under fluctuating light conditions.
Speed Regulation and Gradual Enhancer Switching Models as Flexible and Evolvable Patterning Mechanisms
Authors: Kuhlmann Lukas , El-Sherif Ezzat 
Published: February 2018

Short AbstractUsing simple animations, mathematical formulations, and computational implementation in Matlab, we present a newly devised embryonic patterning mechanism: the Speed Regulation model, and its molecular realization: the Gradual Enhancer Switching model. We show how our models shed light on the phenomenology of insect development and evolution.Long AbstractPartitioning an initially homogeneous group of cells into different fates is a common problem in development. A curious case is the anterior-posterior (AP) fate specification during early embryogenesis in insects. The AP fates of most insects are specified in two different phases: (i) the blastoderm, where the AP axis does not undergo any axial elongation, and (ii) the germband, where the AP axis undergoes gradual axis elongation. Throughout evolution, insects show remarkable flexibility in the number of fates specified in the blastoderm vs germband. This hints that AP specification in insects relies on a flexible mechanism that can pattern both non-elongating embryonic structures (like the blastoderm) and elongating tissues (like the germband). Here we describe the ‘Speed Regulation’ model, a recently suggested patterning mechanism, that can pattern both elongating and non-elongating tissues and ensures the evolvability between them. The model is successful in reproducing the phenomenology of AP axis specification and evolution in insects. In addition, it explains the temporal-based patterning of other embryonic structures like the AP axis of vertebrates and the dorsoventral axis of vertebrate neural tube. The Speed Regulation model is phenomenological in its formulation, in the sense that it does not specify a particular molecular realization. We then present the ‘Gradual Enhancer Switching’ model, in which we describe a specific molecular implementation of the Speed Gradient model that incorporates a novel scheme of cis-regulation within gene regulatory networks. The paper is linked to two videos on YouTube referred to below.Linked VideosVideo I: https://youtu.be/YcGotl8OdYwVideo II: https://youtu.be/f-JnjF2aNLw
Political connections and audit report lag: Indonesian evidence
Authors: Habib Ahsan , Muhammadi Abdul Haris 
Published: February 2018

PurposeThis paper aims to investigate the association between political connections and the audit report lag and whether related party transactions moderate the association between the two.Design/methodology/approachAn ordinary least square regression is estimated whereby audit report lag is regressed on political connections, related party transactions and the interaction between the two. Data on the number and amounts of RPTs are hand-collected from audited financial reports. A firm-year observation is politically connected if at least one large shareholder (controlling at least 10 per cent of the votes directly or indirectly) or board member or commissioner is a current or former Member of Parliament, a minister or head of local government or closely related to a politician or party.FindingsFindings show that the audit report lag is relatively short for politically connected firms but increases when such firms conduct both operating and loan-type related party transactions. This suggests that auditors understand the incentives for, and the implications of, related party transactions and hence exert additional audit efforts in scrutinizing financial statements: activities that will increase the audit report lag.Originality/valueAlthough a large body of empirical research exists on the determinants of audit report lag, none has examined the impact of political connections. This paper further contributes to the auditing literature by documenting auditors’ evaluation of related party transactions in a developing country.
Moderating role of religiosity on Zakat compliance behavior in Nigeria
Authors: Farouk Abubakar U. , Md Idris Kamil , Saad Ram Al Jaffri Bin 
Published: February 2018

Purpose
This paper examines the moderating effect of religiosity in the theory of reasoned action (TRA) on intention to comply with the Zakat on employment income (ZEI).

Design/methodology/approach
A survey of civil servants in Kano State, Nigeria was carried out and 474 valid observations were retrieved from the 700 distributed questionnaires. Partial least squares structural equation modeling (PLS-SEM) was used to validate the instrument that measures the variables, examined the structural model and the predictive relevance of the study’s model.

Findings
The results revealed the suitability of both the TRA and the PLS-SEM in the study of ZEI behavioral intention in a developing country. All the hypothesized direct relationships were supported on the one hand. On the other hand, one of the two indirect relationships, subjective norm and behavioral intention moderated by religiosity was supported, but the other tests for moderating effects of religiosity on the relationship between attitude and behavioral intention was not.

Practical implications
Public and private Zakat institutions in Muslim majority societies in Nigeria and in other Muslim countries may use the findings to focus their attention on the formulation of policies based on the findings of the study to strengthen eligible Zakat payers’ intention to comply to further boost their Zakat collections.

Originality/value
This study extends the TRA in the context of ZEI by proposing religiosity as a moderator in the predictive capacity of TRA on ZEI. Moreover, the suitability for the use of PLS-SEM as a statistical tool in investigating the extended TRA with religiosity as a moderating variable as well as its implications for theory and practice were also discussed.
Development and validation of health service management competencies
Authors: Liang Zhanming , Howard Peter F. , Leggat Sandra , Bartram Timothy 
Published: February 2018

PurposeThe importance of managerial competencies in monitoring and improving the performance of organisational leaders and managers is well accepted. Different processes have been used to identify and develop competency frameworks or models for healthcare managers around the world to meet different contextual needs. The purpose of the paper is to introduce a validated process in management competency identification and development applied in Australia – a process leading to a management competency framework with associated behavioural items that can be used to measure core management competencies of health service managers.Design/methodology/approachThe management competency framework development study incorporated both qualitative and quantitative methods, implemented in four stages, including job description analysis, focus group discussions and online surveys.FindingsThe study confirmed that the four-stage process could identify management competencies and the framework developed is considered reliable and valid for developing a management competency assessment tool that can measure management competence amongst managers in health organisations. In addition, supervisors of health service managers could use the framework to distinguish perceived superior and average performers among managers in health organisations.Practical implicationsDeveloping the core competencies of health service managers is important for management performance improvement and talent management. The six core management competencies identified can be used to guide the design professional development activities for health service managers.Originality/valueThe validated management competency identification and development process can be applied in other countries and different industrial contexts to identify core management competency requirements.
A decision-making model to support the design of a strategic supply chain configuration
Authors: Song Guang , Sun Luoyi , Wang Yixiao 
Published: February 2018

Purpose
The purpose of this paper is to apply an empirically based approach to develop a decision-making model that comprehensively incorporates the potential affecting factors and the related significant drivers that support network designers in selecting the appropriate strategic supply chain configuration or checking the coherence of an existing supply chain structure in four industry sectors.

Design/methodology/approach
The decision-making model is developed based on an empirical study that integrates multiple case studies and statistical analyses. In total, 113 best-in-class manufacturing firms in four sectors are studied to investigate their strategic supply chain configurations and the information of identified affecting drivers. The factor analysis and regression analysis are conducted to classify the drivers into five factor groups, and to identify the significant drivers used to develop the decision-making model.

Findings
The findings of this research are three-pronged. First, 12 significant drivers related to 5 factor groups affecting strategic supply chain network design (SCND) are identified. Second, a decision-making model is developed to support users in strategic SCND. Last, the main characteristics of various strategic supply chain configurations are summarized in four industry sectors.

Research limitations/implications
The authors identified valuable insights for both academics and practitioners based on the identified significant affecting drivers and the developed decision-making model. In addition, this study also proposes two potential research lines on the study of additional contextual affecting factors and decision issues in strategic SCND.

Originality/value
This study could be the first attempt to use an empirically based method to develop a decision-making model aimed at supporting the preliminary design of a supply chain network. Therefore, the drawbacks of a pure qualitative conceptual model and optimization model are eliminated.
Consequences of customer engagement and customer self-brand connection
Authors: Moliner Miguel Ángel , Monferrer-Tirado Diego , Estrada-Guillén Marta 
Published: February 2018

PurposeThe purpose of this paper is to analyze the impact of the customer engagement and customer self-brand connection on customer advocacy and firms’ financial performance. The research focuses on the financial sector and studies a complex organization with a uniform strategy, but which attends the public in different centers (bank branches).Design/methodology/approachA theoretical model of effects is tested using dyadic methodology, with 225 dyads (bank branch manager – average of five customers). The authors use structural equation modeling (EQS6.1) to test the relationships.FindingsThe results corroborate the hypotheses, with the exception of the influence of customer self-brand connection on financial performance. These analyses show that in the banking sector, where the intensive use of new information and technologies has led to a reduction in direct physical contact with the customer, the off-line experience continues to have a notable economic impact. Furthermore, investment in the brand from an experiential approach determines customer advocacy.Originality/valueThe contribution of this paper is twofold. This research analyzes from a theoretical and empirical perspective the impact of the customer engagement and customer self-brand connection on customer advocacy and firms’ financial performance.
Crisis decision-making: the overlap between intuitive and analytical strategies
Authors: Okoli Justin , Watt John 
Published: February 2018

Purpose
The purpose of this paper is to draw on the naturalistic decision making and cognitive science literature to examine how experienced crisis managers utilize the intuitive and analytical strategies when managing complex incidents. A cognitive model that describes the interplay between strategies is presented and discussed, and the specific role that intuition plays in analytical decision making is addressed.

Design/methodology/approach
Designed as a conceptual paper, the extant literature is reviewed to advance discussions on the theme of intuitive and analytical decision making in the naturalistic environment. A new model of expert intuition – the information filtering and intuitive decision model – is presented and evaluated against existing cognitive models from the wider literature.

Findings
The paper suggests that experts’ ability to make intuitive decisions is strongly hinged on their information processing skills that allow irrelevant cues to be sifted out while the relevant cues are retained. The paper further revealed that experts generally employ the intuitive mode as their default strategy, drawing on the analytical mode only as conditions warrant.

Originality/value
Prior research has shown that experts often make important task decisions using intuitive or analytical strategies or by combining both, but the sequence these should typically follow is still unresolved. Findings from the intuition model reveal that although intuition often precedes analytical thinking in almost all cases, both strategies exist to offer significant values to decision makers if the basis of their application is well understood.
Social business as an entrepreneurship model in emerging economy
Authors: Mahfuz Ashraf Md , Razzaque Mohammed Abdur , Liaw Siaw-Teng , Ray Pradeep Kumar , Hasan Md Rashadul 
Published: February 2018

Purpose
Despite its immense potentials as a sustainable and innovative means to solve specific social problems, the basic concept of the social business model (SBM) advanced by Professor Muhammad Yunus remains unclear to many. There exists no literature that objectively compares this model from empowerment and economic growth perspectives with other seemingly similar concepts, such as social enterprise, non-governmental organization (NGO) and corporate social responsibility. Although many NGOs have been showing increasing interest towards the adoption of the SBM to minimize social problems sustainably, lack of conceptual clarity of the model limits the scope of its adoption in addressing social issues. The paper aims to discuss these issues.

Design/methodology/approach
This study is based on a systematic search, analysis and review of literature. It has made use of narrative synthesis of relevant literature on a diverse range of socially oriented models, frameworks and interventions.

Findings
This study identified five key aspects of social business, namely: business’s mission and outcomes, characteristics, operation, resource utilization and environmental considerations. Based on these five key aspects one may like to infer that unlike other social interventions, the alignment of SBM is specific to empowerment of disadvantaged people leading to sustainable economic growth. Analyzing a range of social business interventions in a developing country, Bangladesh, through the lens five key aspects demonstrates that social business is the most efficient way to sustainably maximize the social benefits and minimize specific social issues poverty of the people affected.

Originality/value
This study discusses the scopes of adopting SBM for the socially responsible organizations for sustainable empowerment and economic growth in emerging economies.