bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling the differential dynamics of developmental fate in central and peripheral nervous systems
Authors: Sengupta Dola , Kar Sandip 
Published: September 2016

AbstractBone morphogenetic protein 2 (BMP2), differentially regulates the developmental lineage commitment of neural stem cells (NSC’s) in central and peripheral nervous systems. However, the precise mechanism beneath such observations still remains illusive. To decipher the intricacies of this mechanism, we propose a generic mathematical model of BMP2 driven differentiation regulation of NSC’s. The model efficiently captures the dynamics of the wild-type as well as various mutant and over-expression phenotypes for NSC’s in central nervous system. Our model predicts that the differential developmental dynamics of the NSC’s in peripheral nervous system can be reconciled by altering the relative positions of the two mutually interconnected bi-unstable switches inherently present in the steady state dynamics of the crucial developmental fate regulatory proteins as a function of BMP2 dose. This model thus provides a novel mechanistic insight and has the potential to deliver exciting therapeutic strategies for neuronal regeneration from NSC’s of different origin.
Pleiotropy-robust Mendelian Randomization
Authors: van Kippersluis Hans , Rietveld Cornelius A 
Published: September 2016

AbstractBackgroundThe potential of Mendelian Randomization studies is rapidly expanding due to (i) the growing power of GWAS meta-analyses to detect genetic variants associated with several exposures, and (ii) the increasing availability of these genetic variants in large-scale surveys. However, without a proper biological understanding of the pleiotropic working of genetic variants, a fundamental assumption of Mendelian Randomization (the exclusion restriction) can always be contested.MethodsWe build upon and synthesize recent advances in the econometric literature on instrumental variables (IV) estimation that test and relax the exclusion restriction. Our Pleiotropy-robust Mendelian Randomization (PRMR) method first estimates the degree of pleiotropy, and in turn corrects for it. If a sample exists for which the genetic variants do not affect the exposure, and pleiotropic effects are homogenous, PRMR obtains unbiased estimates of causal effects in case of pleiotropy.ResultsSimulations show that existing MR methods produce biased estimators for realistic forms of pleiotropy. Under the aforementioned assumptions, PRMR produces unbiased estimators. We illustrate the practical use of PRMR by estimating the causal effect of (i) cigarettes smoked per day on Body Mass Index (BMI); (ii) prostate cancer on self-reported health, and (iii) educational attainment on BMI in the UK Biobank data.ConclusionsPRMR allows for instrumental variables that violate the exclusion restriction due to pleiotropy, and corrects for pleiotropy in the estimation of the causal effect. If the degree of pleiotropy is unknown, PRMR can still be used as a sensitivity analysis.Key messagesIf genetic variants have pleiotropic effects, causal estimates of Mendelian Randomization studies will be biased.Pleiotropy-robust Mendelian Randomization (PRMR) produces unbiased causal estimates in case (i) a subsample can be identified for which the genetic variants do not affect the exposure, and (ii) pleiotropic effects are homogenous.If such a subsample does not exist, PRMR can still routinely be reported as a sensitivity analysis in any MR analysis.If pleiotropic effects are not homogenous, PRMR can be used as an informal test to gauge the exclusion restriction.
Regions of very low H3K27me3 partition theDrosophilagenome into topological domains
Authors: El-Sharnouby Sherif , Fischer Bettina , Magbanua Jose Paolo , Umans Benjamin , Flower Rosalyn , Choo Siew Woh , Russell Steven , White Robert 
Published: September 2016

AbstractBackgroundIt is now well established that eukaryote genomes have a common architectural organization into topologically associated domains (TADs) and evidence is accumulating that this organization plays an important role in gene regulation. However, the mechanisms that partition the genome into TADs and the nature of domain boundaries are still poorly understood.ResultsWe have investigated boundary regions in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing mid-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive. The D domains correlate with the boundaries of TADs and are enriched in a subset of architectural proteins, particularly Chromator, BEAF-32, and Z4/Putzig. However, rather than being clustered at the borders of these domains, these proteins bind throughout the H3K27me3-depleted regions and are much more strongly associated with the transcription start sites of housekeeping genes than with the H3K27me3 domain boundaries.ConclusionsWe suggest that the D domain chromatin state, characterised by very low H3K27me3 and established by housekeeping gene regulators, acts to separate topological domains thereby setting up the domain architecture of the genome.
Selection on heterozygosity drives adaptation in intra- and interspecific hybrids
Authors: Smukowski Heil Caiti S. , DeSevo Christopher G. , Pai Dave A. , Tucker Cheryl M. , Hoang Margaret L. , Dunham Maitreya J. 
Published: September 2016

ABSTRACTHybridization is often considered maladaptive, but sometimes hybrids can invade new ecological niches and adapt to novel or stressful environments better than their parents. However, the genomic changes that occur following hybridization and facilitate genome resolution and/or adaptation are not well understood. Here, we address these questions using experimental evolution of de novo interspecific hybrid yeastSaccharomyces cerevisiaexSaccharomyces uvarumand their parentals. We evolved these strains in nutrient limited conditions for hundreds of generations and sequenced the resulting cultures to identify genomic changes. Analysis of 16 hybrid clones and 16 parental clones identified numerous point mutations, copy number changes, and loss of heterozygosity events, including a number of nuclear-mitochondrial mutations and species biased amplification of nutrient transporters. We focused on a particularly interesting example, in which we saw repeated loss of heterozygosity at the high affinity phosphate transporter genePHO84in both intra- and interspecific hybrids. Using allele replacement methods, we tested the fitness of different alleles in hybrid andS. cerevisiaestrain backgrounds and found that the loss of heterozygosity is indeed the result of selection on one allele over the other in bothS. cerevisiaeand the hybrids. This illuminates an example where hybrid genome resolution is driven by positive selection on existing heterozygosity, and generally demonstrates that outcrossing need not be frequent to have long lasting impacts on adaptation.
Natural Variation in ArabidopsisCvi-0 Accession Uncovers Regulation of Guard Cell CO2Signaling by MPK12
Authors: Jakobson Liina , Vaahtera Lauri , Tõldsepp Kadri , Nuhkat Maris , Wang Cun , Wang Yuh-Shuh , Hõrak Hanna , Valk Ervin , Pechter Priit , Sindarovska Yana , Tang Jing , Xiao Chuanlei , Xu Yang , Gerst Talas Ulvi , Remm Maido , Kangasjärvi Saijaliisa , Roelfsema M. Rob G. , Hu Honghong , Kangasjärvi Jaakko , Loog Mart , Schroeder Julian I. , Kollist Hannes , Brosché Mikael 
Published: September 2016

AbstractPlant gas exchange is regulated by guard cells that form stomatal pores. Stomatal adjustments are crucial for plant survival; they regulate uptake of CO2for photosynthesis, loss of water and entrance of air pollutants such as ozone. We mapped ozone hypersensitivity, more open stomata and stomatal CO2-insensitivity phenotypes of theArabidopsis thalianaaccession Cvi-0 to a single amino acid substitution in MAP kinase 12 (MPK12). In parallel we showed that stomatal CO2-insensitivity phenotypes of a mutantcis(CO2-insensitive) were caused by a deletion ofMPK12. Lack of MPK12 impaired bicarbonate-induced activation of S-type anion channels. We demonstrated that MPK12 interacted with the protein kinase HT1, a central node in guard cell CO2signaling, and that MPK12 can function as an inhibitor of HT1. These data provide a new function for plant MPKs as protein kinase inhibitors and suggest a mechanism through which guard cell CO2signaling controls plant water management.
Activity of theC. elegansegg-laying behavior circuit is controlled by competing activation and feedback inhibition
Authors: Collins Kevin M. , Bode Addys , Fernandez Robert W. , Tanis Jessica E. , Brewer Jacob , Creamer Matthew S. , Koelle Michael R. 
Published: September 2016

AbstractLike many behaviors,Caenorhabditis elegansegg laying alternates between inactive and active states. To understand how the underlying neural circuit turns the behavior on and off, we optically recorded circuit activity in behaving animals while manipulating circuit function using mutations, optogenetics, and drugs. In the active state, the circuit shows rhythmic activity phased with the body bends of locomotion. The serotonergic HSN command neurons initiate the active state, but accumulation of unlaid eggs also promotes the active state independent of the HSNs. The cholinergic VC motor neurons slow locomotion during egg-laying muscle contraction and egg release. The uv1 neuroendocrine cells mechanically sense passage of eggs through the vulva and release tyramine to inhibit egg laying, in part via the LGC-55 tyramine-gated Cl−channel on the HSNs. Our results identify discrete signals that entrain or detach the circuit from the locomotion central pattern generator to produce active and inactive states.
Making projects critical 15 years on: a retrospective reflection (2001-2016)
Authors: Hodgson Damian , Cicmil Svetlana 
Published: September 2016

PurposeThe purpose of this paper is to review the formation and evolution of the “Making Projects Critical” movement in project management research.Design/methodology/approachRetrospective and discursive paper.FindingsReflections on tensions and challenges faced by the MPC movement.Originality/valueThe paper establishes the historical trajectory of this movement and clarifies the tensions and challenges faced by MPC.
Fast damaging processes in the TaN thin film absorbers under action of nanosecond electrical pulses
Authors: Ardaravičius Linas , Keršulis Skirmantas , Kiprijanovič Oleg , Šimkevicius Česlovas , Vengalis Bonifacas 
Published: September 2016

Purpose
The purpose of this paper is to investigate damaging processes in TaN thin film absorbers under action of high-voltage electrical pulse of nanosecond duration. Despite having mechanical origin of crack opening, estimation based on the readings from oscillograms shows uncharacteristically high velocities of the crack propagation.

Design/methodology/approach
Microscopic images of damaged absorbers showing the final result of the damaging process provided initial information about its geometrical peculiarities. Then, to clarify the dynamics of the process, the authors create the model of the crack, having elements of self-similarities and multiple stage opening. The influence of heating induced by current concentration at crack tip and of magnetic stress of this concentrated current are both included in the model.

Findings
Using physical parameters of TaN layers with flowing current and performing calculations the authors define the conditions required to initiate the damaging process and to sustain it. Danger of such damage is relevant for high-Tc superconducting thin films after their switching to normal state which is induced by the high-voltage pulse.

Practical implications
There were made recommendations to manufactures aiming to improve electrical durability of the absorbers in an effort to prevent the damaging influence of power nanosecond electrical pulses.

Originality/value
Three stage opening model implies the appearance of zone of high-energy dissipation that can lead to detonation-like destruction of the film and, therefore, explain the high velocities of crack propagation.
Influence of country image on country brand equity: application to higher education services
Authors: Herrero-Crespo Ángel , San Martín Gutiérrez Héctor , Garcia-Salmones Maria del Mar 
Published: September 2016

Purpose
The purpose of this paper is to analyze how country image affects the dimensions of country brand equity (CBE) (i.e. awareness, image, perceived quality and loyalty) in the higher education sector, as well as the interrelationships between these dimensions.

Design/methodology/approach
Quantitative research with 208 international students who were starting the academic year at a Spanish university was performed to test the hypotheses. In accordance with the characteristics of the target population, the subjects interviewed were mainly from Europe and the Americas.

Findings
The results indicate that the country image affects the perceived quality and awareness of the universities in the country. Additionally, a hierarchy of effects between the dimensions of CBE was found. In particular, loyalty toward the universities of a country is positively influenced by their perceived quality, which is affected by image and awareness of these universities. For its part, the image of universities is positively influenced by the awareness attributed to them by international students.

Practical implications
These results have implications for marketing activities aimed at the internationalization of higher education institutions and, therefore, their appeal to international students.

Originality/value
The paper’s findings represent an important step in the advancement of knowledge about CBE by taking as a basis a complex model that involves the different dimensions of this construct together with a relevant variable in international marketing, that is, country image.
Here, there and everywhere: a study of consumer centrism
Authors: Prince Melvin , Davies Mark A.P. , Cleveland Mark , Palihawadana Dayananda 
Published: September 2016

Purpose
A first objective is to add insight into how constructs of ethnocentrism, xenocentrism and cosmopolitanism relate to each other. Knowledge of how these constructs overlap or work together in affecting consumer preferences will offer global marketers insights for designing appropriate marketing strategies. The second objective is to extend this knowledge by examining the correspondence of these three constructs to a nomological network of dispositional concepts pertinent for product positioning and market segmentation. The third objective is to empirically examine the extent to which the measures, construct structure and associative relationships are robust in different national research settings. The paper aims to discuss these issues.

Design/methodology/approach
Surveying British and American consumers, this study examines and analyzes the correspondence of these identity-relevant constructs within a nomological net of pertinent concepts: consciousness-of-kind, global consumption orientation, materialism and natural environment concern.

Findings
The hypothesized negative links between CET-XEN and CET-COS, and the predicted positive connection between XEN-COS were all confirmed on the latent factor results for the combined data set. The negative correlation between CET-XEN was of a considerably lower magnitude than that for CET-COS.

Originality/value
To date, no research has used an identity theory framework and simultaneously examined in a cross-cultural context the interrelationships of consumer ethnocentrism consumer xenocentrism and cosmopolitanism – and their differentiating linkages to a multiplicity of consumer dispositions.
Maltese certified public accountants and whistle-blowing: traits, influences and propensity
Authors: Francalanza Charles , Buttigieg Emanuela 
Published: September 2016

Purpose
The purpose of this paper is to deal with an important element of the whistle-blowing decision, the whistle-blower. It is set within the environment of the small Mediterranean island of Malta. It has two objectives. The first is to identify the more important personality traits of the potential Maltese accountant whistle-blower and the situational factors that mostly affect his/her whistle-blowing decision. The second objective is to develop a regression model that can be used to identify the potential Maltese accountant whistle-blower.

Design/methodology/approach
The study is in the form of two e-mail questionnaires sent to Maltese accounting practitioners.

Findings
The personality traits of conscientiousness, openness to experience and extraversion and the situational factors of ethical considerations and professional requirements were found to be the more significant. The regression model proved substantially correct in singling out the potential Maltese accountant whistle-blower.

Research limitations/implications
The results are based on the replies of respondents to two questionnaires and not actual whistle-blowing behaviour. Also, the propensity to be a whistle-blower or not may not be a constant since it can be affected by shifts in internal attributes and situational factors.

Practical implications
Besides academic qualifications, the personality of the individual and his/her potential reaction to the working environment should be given due consideration in the recruitment of accounting staff.

Originality/value
The research contributes to the literature on the accountant whistle-blower in a small country setting that is rarely the subject of study.
Corporate share repurchases in the UK
Authors: Dhanani Alpa 
Published: September 2016

Purpose
The purpose of this paper is to examine motivations underlying UK repurchase activity. Specifically, the paper inquires into the relevance of a range of different explanations for repurchases and perceptions of regulation surrounding them. Emphasis of the paper is, however, on motives linked specifically to repurchases rather than income distribution, more generally.

Design/methodology/approach
The study uses a survey approach to capture the views on repurchases of corporate managers and investors. It supplements the survey data with secondary information about the companies to better understand repurchase behaviour.

Findings
Results indicate that repurchase use is influenced by motives linked specifically to this tool rather than those associated with income distribution, more generally. In particular, repurchases are used to return surplus cash to investors, signal undervaluation and influence gearing and earnings per share levels. In the latter case, companies appear to use repurchases to perform a value added role, alongside manipulating the EPS level and thus the latter may simply be a by-product of the former. Private investors may nevertheless be vulnerable to such manipulation, given their limited financial literacy.

Research limitations/implications
The study relied on a survey of managers and investors and univariate analysis. In the former case, respondent numbers, particularly for the investor community were low, raising questions as to the generalisability of the data. In the latter, the results may be mis-stated owing to the simplicity of the analysis.

Practical implications
Overall, the survey results suggest that firms use repurchase programmes in different contexts to dividend payments and in appropriate circumstances. While managers and investors broadly share similar views, private shareholders may be in a vulnerable position given their limited financial literacy.

Originality/value
This is the first UK study on repurchases that examines the relative importance of a range of motives underlying repurchases. Moreover, it assesses in detail the core hypotheses that are linked specifically to repurchase programmes to better understand UK repurchase behaviour. It does so by supplementing the survey data with additional company information and comparing the views of the different audiences surveyed.
Tax reforms and revenue mobilization in Ghana
Authors: Bekoe William , Danquah Michael , Senahey Sampson Kwabena 
Published: September 2016

PurposeThe purpose of this paper is to comprehensively examine Ghana’s tax reform programme and investigate whether it has facilitated the revenue mobilization capacity of the overall tax system and of individual taxes on the basis of estimates of tax buoyancies and elasticities.Design/methodology/approachThis study uses the proportional adjustment approach to estimate tax buoyancies and elasticities of the overall tax system and of individual taxes for the pre and post tax reform period over the 1970-2013 period.FindingsThe results show that in general, tax reforms had a positive influence on the overall tax structure and on the individual tax handles as evidenced in the more than unity buoyancy and elasticity. All the individual taxes, except excise duties, recorded buoyancies and elasticities of more than unity during the reform period.Practical implicationsTax authorities ought to move away from income-based taxation which discriminates against saving and investment, in favour of consumption-based taxes in conformity with international standards. Emphasis must also be placed on those taxes that have high revenue elasticities. These taxes include the personal, corporate, the Value Added Tax, and the import duties.Originality/valueIn this study, the paper extends and disaggregates the data on taxes, account for discretionary tax changes from the historical time series data, and use the adjusted historical time series data to estimate tax elasticity. The study therefore provides an in-depth understanding of the effects of the tax reforms on the overall tax system and of individual taxes in Ghana.
Monetary decentralization in the United States: is there a case for multiple currencies?
Authors: Chupp Benjamin Andrew 
Published: September 2016

Purpose
When sectoral shocks hit a large, regionally heterogeneous economy, it is likely that regions with sectoral specialization will be affected in different ways. In these cases, it might be optimal for the country to decentralize the currency into a number of regional currencies, thus allowing for differentiated monetary policy. The paper aims to discuss these issues.

Design/methodology/approach
The author explicates the potential benefits and costs to decentralization. The author also highlights characteristics that should be satisfied in order to consider multiple currencies. This paper uses a theoretical and empirical model to test if the USA contains regional optimal currency areas. The author tests five potential divisions of the states into monetary subunions.

Findings
One of these divisions is proven to result in higher welfare (a 2 percent increase) than the status quo national monetary union. Thus, the USA is not an optimal currency area, and monetary decentralization could be a feasible and welfare-improving option for future policy.

Originality/value
There have been no previous studies of monetary divisions. Given the importance of fiscal decentralization, it is important to also understand the implications of monetary decentralization.