bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformational distributions of isolated myosin motor domains encode their mechanochemical properties
Authors: Porter Justin R. , Meller Artur , Zimmerman Maxwell I. , Greenberg Michael J. , Bowman Gregory R. 
Published: December 2019

AbstractMyosin motor domains perform an extraordinary diversity of biological functions despite sharing a common mechanochemical cycle. Motors are adapted to their function, in part, by tuning the thermodynamics and kinetics of steps in this cycle. However, it remains unclear how sequence encodes these differences, since biochemically distinct motors often have nearly indistinguishable crystal structures. We hypothesized that sequences produce distinct biochemical phenotypes by modulating the relative probabilities of an ensemble of conformations primed for different functional roles. To test this hypothesis, we modeled the distribution of conformations for twelve myosin motor domains by building Markov state models (MSMs) from an unprecedented two milliseconds of all-atom, explicit-solvent molecular dynamics simulations. Comparing motors reveals shifts in the balance between nucleotide-favorable and nucleotide-unfavorable P-loop conformations that predict experimentally-measured duty ratios and ADP release rates better than sequence or individual structures. This result demonstrates the power of an ensemble perspective for interrogating sequence-function relationships.Subject AreasBiochemistry and Chemical Biology, Structural Biology and Molecular Physics
Hierarchical Markov Random Field model captures spatial dependency in gene expression, demonstrating regulation via the 3D genome
Authors: Zhou Naihui , Friedberg Iddo , Kaiser Mark S. 
Published: December 2019

AbstractHiC technology has revealed many details about the eukaryotic genome’s complex 3D architecture. It has been shown that the genome is separated into organizational structures which are associated with gene expression. However, to the best of our knowledge, no studies have quantitatively measured the level of gene expression in the context of the 3D genome.Here we present a novel model that integrates data from RNA-seq and HiC experiments, and determines how much of the variation in gene expression can be accounted for by the genes’ spatial locations. We used Poisson hierarchical Markov Random Field (PhiMRF), to estimate the level of spatial dependency among protein-coding genes in two different human cell lines. The inference of PhiMRF follows a Bayesian framework, and we introduce the Spatial Interaction Estimate (SIE) to measure the strength of spatial dependency in gene expression.We find that the quantitative expression of genes in some chromosomes show meaningful positive intra-chromosomal spatial dependency. Interestingly, the spatial dependency is much stronger than the dependency based on linear gene neighborhoods, suggesting that 3D chromosome structures such as chromatin loops and Topologically Associating Domains (TADs) are strongly associated with gene expression levels. In some chromosomes the spatial dependency in gene expression is only detectable when the spatial neighborhoods are confined within TADs, suggesting TAD boundaries serve as insulating barriers for spatial gene regulation in the genome. We also report high inter-chromosomal spatial correlations in the majority of chromosome pairs, as well as the whole genome. Some functional groups of genes show strong spatial dependency in gene expression as well, providing new insights into the regulation mechanisms of these molecular functions. This study both confirms and quantifies widespread spatial correlation in gene expression. We propose that, with the growing influx of HiC data complementing gene expression data, the use of spatial dependence should be an integral part of the toolkit in the computational analysis of the relationship between chromosome structure and gene expression.
High fat diet worsens pathology and impairment in an Alzheimer’s mouse model, but not by synergistically decreasing cerebral blood flow
Authors: Bracko Oliver , Vinarcsik Lindsay K. , Cruz Hernández Jean C. , Ruiz-Uribe Nancy E. , Haft-Javaherian Mohammad , Falkenhain Kaja , Ramanauskaite Egle M. , Ali Muhammad , Mohapatra Aditi , Swallow Madisen , Njiru Brendah N. , Muse Victorine ,   Stall Catchers contributors, Michelucci Pietro E. , Nishimura Nozomi , Schaffer Chris B. 
Published: December 2019

AbstractObesity is linked to increased risk for and severity of Alzheimer’s disease (AD). Cerebral blood flow (CBF) reductions are an early feature of AD and are also linked to obesity. We showed that non-flowing capillaries, caused by adhered neutrophils, underlie the CBF reduction in mouse models of AD. Because obesity could exacerbate the vascular inflammation likely underlying this neutrophil adhesion, we tested links between obesity and AD by feeding APP/PS1 mice a high fat diet (Hfd) and evaluating behavioral, physiological, and pathological changes. We found trends toward poorer memory performance in APP/PS1 mice fed a Hfd, impaired social interactions with either APP/PS1 genotype or a Hfd, and synergistic impairment of sensory-motor function in APP/PS1 mice fed a Hfd. The Hfd led to increases in amyloid-beta monomers and plaques in APP/PS1 mice, as well as increased brain inflammation. These results agree with previous reports showing obesity exacerbates AD-related pathology and symptoms in mice. We used a crowd-sourced, citizen science approach to analyze imaging data to determine the impact of the APP/PS1 genotype and a Hfd capillary stalling and CBF. Surprisingly, we did not see an increase in the number of non-flowing capillaries or a worsening of the CBF deficit in APP/PS1 mice fed a Hfd as compared to controls, suggesting capillary stalling is not a mechanistic link between a Hfd and increased severity of AD in mice. Reducing capillary stalling by blocking neutrophil adhesion improved CBF and short-term memory function in APP/PS1 mice, even when fed a Hfd.Significance statementObesity, especially in mid-life, has been linked to increased risk for and severity of Alzheimer’s disease. Here, we show that blocking adhesion of white blood cells leads to increases in brain blood flow that improve cognitive function, regardless of whether mice are obese or not.
Understanding power-related strategies and initiatives
Authors: Contrafatto Massimo , Ferguson John , Power David , Stevenson Lorna , Collison David 
Published: December 2019

PurposeThe purpose of this paper is to provide a theoretically informed analysis of a struggle for power over the regulation of corporate social responsibility (CSR) and social and environmental accounting and reporting (SEAR) within the European Union.Design/methodology/approachThe paper combines insights from institutional theory (Lawrence and Buchanan, 2017) with Vaaraet al.’s (2006) and Vaara and Tienar’s (2008) discursive strategies approach in order to interrogate the dynamics of the institutional “arena” that emerged in 2001, following the European Commission’s publication of a Green Paper (GP) on CSR policy and reporting. Drawing on multiple sources of data (including newspaper coverage, semi-structured interviews and written submissions by companies and NGOs), the authors analyse the institutional political strategies employed by companies and NGOs – two of the key stakeholder groupings who sought to influence the dynamics and outcome of the European initiative.FindingsThe results show that the 2001 GP was a “triggering event” (Hoffman, 1999) that led to the formation of the institutional arena that centred on whether CSR policy and reporting should be voluntary or mandatory. The findings highlight how two separate, but related forms of power (systemic and episodic power) were exercised much more effectively by companies compared to NGOs. The analysis of the power initiatives and discursive strategies deployed in the arena provides a theoretically informed understanding of the ways in which companies acted in concert to reach their objective of maintaining CSR and SEAR as a voluntary activity.Originality/valueThe theoretical framework outlined in the paper highlights how the analysis of CSR and SEAR regulation can be enriched by examining the deployment of episodic and systemic power by relevant actors.
User willingness to purchase applications on mobile intelligent devices: evidence from app store
Authors: Tang Jie , Zhang Bin , Akram Umair 
Published: December 2019

PurposeThe purpose of this paper is to explore the facilitating and inhibitory factors on paid app downloading intentions based on an integrated valence theory, considering two social environmental factors and two intermediate variables: perceived value and perceived trust.Design/methodology/approachThis study is based on the integrated valence theory. After collecting users’ data, partial least square analysis is used to examine the main driving and constraining factors for users to download paid apps in Apple mobile devices.FindingsThe empirical results show that mediated through perceived value, perceived usefulness and perceived compatibility are the absolute positive factors that affect user’s willingness to purchase apps, whereas perceived cost is the main barrier for users to do so. Social environment where the users are in also plays an important role in their purchase intentions.Practical implicationsThis study hopes to offer guidance to paid app developers and general app markets, and to help expand the consumer group, make the purchase experience more efficient and promote the development of paid app market.Originality/valueThe finding not only enriches the adoption theory of mobile apps from the perspective of valence theory, but also provides pricing and functional suggestions for platform suppliers and software developers of paid apps.
Motivations for prescription drug use in a marginalised open drug scene
Authors: Sultan Aysel , Werse Bernd 
Published: December 2019

Purpose
The purpose of this paper is to explore prevalence, contexts and motives for the use of various benzodiazepines, sedatives and opioids among injection drug users in Frankfurt’s open drug scene.

Design/methodology/approach
The paper uses quantitative data from ten waves of the bi-annual open drug scene survey carried out within the frames of the Frankfurt local drug monitoring system (MoSyD) and an additional sample of qualitative interviews to highlight the individual user perspectives as well as professional insights.

Findings
The results suggest that the prescription drugs act as “support drugs” when the drugs of choice are not available or affordable. Patterns of use also show that by acting to manage withdrawal symptoms, insomnia and relieving stress, prescription drugs also contribute to maintaining daily functionality.

Originality/value
The paper contributes to the discussion on the motives and functions of prescription drug use in an urban open drug scene.
Financing constraints of public–private partnership projects in India
Authors: Sinha Ajit Kumar , Jha Kumar Neeraj 
Published: December 2019

PurposeThe purpose of this paper is to identify the problems faced by banks, lenders, financial institutions, public authority, developers and concessionaires in course of financing of public–private partnership (PPP) road projects. Subsequently, the reasons that contribute to these problems were analyzed to come up with recommendations for mitigation of these problems.Design/methodology/approachThe methodology adopted is based on identification of financing problems and the reasons thereof, from a systematic and critical review of literature. Financing details including problems faced and reasons behind were extracted from details of one port, one airport and one road project. Data pertaining to financing of PPP road projects have been collected for completed (five projects) as well as projects under implementation (five projects) during a time interval of four months, starting from December 2018 to March 2019. The chosen three projects for case studies were executed in airport project at Kolkata in four years, offshore container terminal at Mumbai port in six years and Tuni Ankapali road project in three years. This period attains importance, as simultaneous progressive development and innovation in the PPP mode of project execution was taking place rapidly.FindingsThe commercial banks in India dominate in providing debt to the PPP infrastructure projects, especially in the road sector. The non-banking financial companies and other intermediaries were still in their infancy then, and a corporate bond market was growing steadily, though slowly. Financing problems faced by the developers resulted in unwarranted time and cost overruns emanating from delay in land acquisition and grant of approvals, with these being the two major barriers to private sector participation. Even schedule overrun finally resulted in increased construction and financing cost.Originality/valueDemand for upgradation, building and expansion of transportation infrastructure (roads) exists to keep pace with economic development. Problems like lack of a developed market for financing, inadequate institutional capacity, lack of personnel having domain expertise and absence of exclusive legislation to govern the implementation of PPP road projects are encountered by the sponsors and developers. Delay in land acquisition and environment clearance inhibits any decisive action by the lenders and investors, as these two are integrally linked to the decisions to be taken with respect to the financing of projects. Investors and bankers are generally apprehensive of their investment getting locked in or ending up as non-performing assets. Identification and proposed mitigation of these problems may likely smoothen the rough edges for the financing of projects, resulting in smoother implementation.
The path to sustainability
Authors: Darus Faizah , Mohd Zuki Hidayatul Izati , Yusoff Haslinda 
Published: December 2019

Purpose
Climate change has become an increasingly important issue globally, and organisations are being urged to be more carbon friendly by taking initiatives to reduce carbon emissions in their business operations. The purpose of this paper is to examine the extent to which climate change has been addressed and the influence of financial strength and corporate governance structure on the disclosure of carbon information.

Design/methodology/approach
The research process consists of an investigation via content analysis of the annual and sustainability reports of the top 100 public-listed companies in Malaysia for the year 2017.

Findings
The results of the study revealed that carbon information on carbon emissions accounting had the highest disclosure and that climate change risks and opportunities had the lowest disclosure. The results of the multiple regression analysis revealed that profitability is positively significant with carbon disclosure while leverage is negatively significant. However, the governance structure does not seem to have any influence on the disclosure of carbon information.

Research limitations/implications
The conclusions drawn from the study must be interpreted with caution as the sample companies only comprise of the top 100 public-listed companies in Malaysia to provide an initial insight into the situation in Malaysia. Furthermore, the interpretations and conclusions drawn from this study are based solely on a cross-sectional analysis of the data for only one year.

Practical implications
This finding is a significant contribution to regulatory bodies and policymakers regarding the drivers of climate change initiatives in an emerging economy such as Malaysia. This finding suggests that in the Malaysian setting, financial structure influence decisions on climate change initiatives.

Social implications
The commitment by business leaders of the impact on climate from the production processes would contribute towards a low carbon economy and subsequently improve the quality of life of the community.

Originality/value
The findings of the study provide insight of the business attitude towards climate change in an emerging economy such as Malaysia.
The dark side of social media connectivity
Authors: Tang Guiyao , Ren Shuang , Chadee Doren , Yuan Shuo 
Published: December 2019

PurposeThe increasing use of social media after work hours for work purposes, termed social media connectivity (SMC), is an emerging phenomenon in supply chain management. Although SMC can have debilitating effects on supply chain professionals and their organizations, research on its effects on work-related attitudes, especially turnover intentions, remains largely unexplored. The purpose of this paper is to investigate the influence of SMC on voluntary turnover of supply chain professionals and the resulting implications for them and their organizations.Design/methodology/approachThe study draws from the conservation of resources theory and the concept of information overload to explain how SMC leads to emotional exhaustion and impacts turnover intentions of supply chain professionals, contingent on work–life balance. The model is tested using survey data (n=325) collected at multiple times from a large Chinese pharmaceutical manufacturer and distributor with spatially dispersed workforce and distribution facilities.FindingsThe results confirm that emotional exhaustion mediates the association between SMC and turnover intentions and that SMC exacerbates the intentions of supply chain professionals to quit their jobs. However, work–life balance is found to dampen the exhausting effects of SMC on emotional exhaustion thereby reducing its debilitating effects on turnover intentions of supply chain professionals.Originality/valueThe focus on SMC highlights the need for greater understanding of the dark side of social media on supply chain professionals and their organizations and how SMC can be better managed in an age of social media ubiquity.
Cross-border B2C e-commerce to China
Authors: Giuffrida Maria , Mangiaracina Riccardo , Perego Alessandro , Tumino Angela 
Published: December 2019

Purpose
The purpose of this paper is to support companies’ risk-informed selection of a logistics solution to operate in China via cross-border e-commerce (CBEC).

Design/methodology/approach
Decision theory is applied to the recent field of CBEC. This theoretic setup involves a decision maker who must choose among a set of alternatives, whose consequences depend on uncertain factors (Savage, 1954). The study develops an activity-based model to calculate logistics costs in a deterministic setting. Simulations and probabilistic sensitivity analyses are later performed to evaluate the impact of uncertainty.

Findings
There are four main solutions to enter China, determined by the adopted international transport mean and the presence of a local warehouse. The most important risk factors affecting the choice of the logistics solution are change of CBEC regulation, product value, expected service level and demand level.

Originality/value
From a theoretical perspective, this study improves CBEC literature, so far characterised by descriptive papers, often lacking industry focus or empirical exploration. It also provides new application opportunities for decision theory, whereas previous contributions have proposed different theoretical approaches, such as transaction cost or institutional theory. From a practical viewpoint, the paper is the first to compare the costs of the main logistics solutions to sell online to China, by taking uncertainty into account. The results can be used to better understand the differences among solutions and identify the most critical parameters. Finally, this research provides some observations for policy implementation.
Applying quantile regression to determine the effects of household characteristics on household saving rates in Vietnam
Authors: Hua Thanh Xuan , Erreygers Guido 
Published: December 2019

Purpose
The purpose of this paper is to analyse the determinants of the saving behaviour of Vietnamese households and to explore the possible heterogeneity of household saving propensities.

Design/methodology/approach
The authors estimate the effects of household characteristics on Vietnamese household saving rates by means of a quantile regression approach using the Vietnam Household Living Standard Survey 2010 data set.

Findings
The results suggest that the way household characteristics influence saving rates is different for each quantile of the household saving rate distribution. Household characteristics tend to have stronger effects at lower quantiles. Particularly, the marginal propensity to save of households at low quantiles is higher than those at high quantiles. Analysing rural and urban households separately, the authors find evidence that household and household head characteristics have stronger significant effects for rural than for urban households. Children and elderly members should be treated as part of the household labour force, instead of household dependency, since both of them increase household saving rates.

Originality/value
This research contributes to the literature on Vietnamese household saving behaviours, especially for households living in urban areas.
How good is the marketing method? Measuring the process and the outcomes
Authors: Pimenta da Gama António 
Published: December 2019

Purpose
Marketing performance assessment has been a major concern and remains a vital issue for companies and professionals. This paper aims to revisit the theme of marketing audits and propose a methodological approach aimed to evaluate marketing practice at the light of the processes involved.

Design/methodology/approach
The paper is structured in three parts. It begins with an overview of marketing audit’s theoretical domain. Then, the rationale, content and implementation of the instrument are presented. Finally, the work’s main motivations and implications are discussed.

Findings
To turn assessment into a useful exercise, it is necessary the existence of a framework allowing a common language for describing marketing practice. The author believes that a structured approach for evaluating marketing processes can decisively influence marketing effectiveness.

Research limitations/implications
This work provided a theoretically anchored methodology for evaluating marketing practice. As such, it lays down the foundations for further research on the relevance of the selected processes and how they translate in future consequences for the business.

Practical implications
The view presented is intended to draw attention to the need for assessing the way marketing is executed, providing an instrument that helps professionals to better develop their activity and improve their contribution to business success.

Originality/value
Most existing marketing performance measures focus on outputs. However, results, per se, say little about the reasons of success or failure. This paper reinforces the importance of marketing audits as a tool to evaluate the way marketing processes are developed within an organization