bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage Disequilibrium Estimation in Low Coverage High-Throughput Sequencing Data
Authors: Bilton Timothy P. , McEwan John C. , Clarke Shannon M. , Brauning Rudiger , van Stijn Tracey C. , Rowe Suzanne J. , Dodds Ken G. 
Published: December 2017

AbstractHigh-throughput sequencing methods that multiplex a large number of individuals have provided a cost-effective approach for discovering genome-wide genetic variation in large populations. These sequencing methods are increasingly being utilized in population genetic studies across a diverse range of species. One side-effect of these methods, however, is that one or more alleles at a particular locus may not be sequenced, particularly when the sequencing depth is low, resulting in some heterozygous genotypes being called as homozygous. Under-called heterozygous genotypes have a profound effect on the estimation of linkage disequilibrium and, if not taken into account, leads to inaccurate estimates. We developed a new likelihood method, GUS-LD, to estimate pairwise linkage disequilibrium using low coverage sequencing data that accounts for under-called heterozygous genotypes. Our findings show that accurate estimates were obtained using GUS-LD on low coverage sequencing data, whereas underestimation of linkage disequilibrium results if no adjustment is made for under-called heterozygotes.
Mushroom body-specific profiling of gene expression identifies regulators of long-term memory inDrosophila
Authors: Widmer Yves F , Bilican Adem , Bruggmann Rémy , Sprecher Simon G 
Published: December 2017

AbstractMemory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. WithDrosophila melanogasteras a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. Forvajk-1andhacd1, the two strongest hits, we gained further support for their crucial role in learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases.
Random Forest Feature Selection, Fusion and Ensemble Strategy: Combining Multiple Morphological MRI Measures to Discriminate among healthy elderly, MCI, cMCI and Alzheimer's disease patients: from the Alzheimer’s disease neuroimaging initiative (ADNI) database
Authors: Dimitriadis S.I. , Liparas D. , Tsolaki Magda N. 
Published: December 2017

AbstractBackgroundIn the era of computer-assisted diagnostic tools for various brain diseases, Alzheimer’s disease (AD) covers a large percentage of neuroimaging research, with the main scope being its use in daily practice. However, there has been no study attempting to simultaneously discriminate among Healthy Controls (HC), early mild cognitive impairment (MCI), late MCI (cMCI) and stable AD, using features derived from a single modality, namely MRI.New MethodBased on preprocessed MRI images from the organizers of a neuroimaging challenge2, we attempted to quantify the prediction accuracy of multiple morphological MRI features to simultaneously discriminate among HC, MCI, cMCI and AD. We explored the efficacy of a novel scheme that includes multiple feature selections via Random Forest from subsets of the whole set of features (e.g. whole set, left/right hemisphere etc.), Random Forest classification using a fusion approach and ensemble classification via majority voting.From the ADNI database, 60 HC, 60 MCI, 60 cMCI and 60 AD were used as a training set with known labels. An extra dataset of 160 subjects (HC: 40, MCI: 40, cMCI: 40 and AD: 40) was used as an external blind validation dataset to evaluate the proposed machine learning scheme.ResultsIn the second blind dataset, we succeeded in a four-class classification of 61.9% by combining MRI-based features with a Random Forest-based Ensemble Strategy. We achieved the best classification accuracy of all teams that participated in this neuroimaging competition.Comparison with Existing Method(s)The results demonstrate the effectiveness of the proposed scheme to simultaneously discriminate among four groups using morphological MRI features for the very first time in the literature.ConclusionsHence, the proposed machine learning scheme can be used to define single and multi-modal biomarkers for AD.HIGHLIGHTS1stplace in International Challenge for Automated Prediction of MCI from MRI DataMulti-class classification of normal control, MCI, converting MCI, and Alzheimer’s diseaseMorphometric measures from 3D T1 brain MRI images have been analysed (ADNI1 cohort).ARandom Forest Feature Selection, Fusion and Ensemble Strategywas applied to classification and prediction of AD.Accuracy and robustness have been assessed in a blind dataset
Computational Model for Simulating Drug-Induced Arrhythmia Sensitivity of Human iPSC-derived Cardiomyocytes
Authors: Gao Xin , Yin Yue , Daily Neil , Engel Tyler , Pang Li , Carlson Brian E. , Wakatsuki Tetsuro 
Published: December 2017

AbstractA mathematical model describing the electrophysiology and ion handling of cardiomyocytes is a complement to experimental analysis predicting drug-induced proarrhythmic potential in humans as proposed by Comprehensive in vitro Proarrhythmia Assay (CiPA). While CiPA endorses the use of the O’Hara Rudy (ORd) model, which was developed to simulate electrophysiology of human adult ventricular cardiomyocytes (hAVCMs), to predict drug-induced proarrhythmias; the human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) was proposed for experimental verifications. The hiPSC-CMs, especially cultured in 2D culture dishes, are inherently different from hAVCMs exhibiting different ion channel density and an immature sarcoplasmic reticulum function. To reconcile this mismatch, we have developed a mathematical electrophysiology model of an hiPSC-CM by incorporating differences in gene expressions of ion channels, pumps and receptors in hiPSC-CMs against those found in hAVCMs. This model can be used to model any hiPSC-CM cell line where expression data has been obtained and replaces the background currents for K+ and Na+ in the ORd model with the known ultra-rapid K+ channel and hyperpolarization activated K+/Na+ channel currents. With this new model, three batches each from two different hiPSC-CM cell lines are compared to experimental data of action potential duration. This mathematical model recapitulates a ventricular-like action potential morphology with a Phase 2 plateau lasting a few hundred milliseconds. However, the resting membrane potential is not as depolarized (−65 to −70 mV) as that of hAVCM (-80 mV). The elevated resting membrane potential matches experimental data previously and is thought to keep rapid sodium channels from triggering membrane depolarization instead being replaced by an overexpression of L-Type Ca2+ channel current. This model is a key step in identifying the variability between different hiPSC-CM lines and even batches of the same line, opening the door to realizing analysis of patient specific preparations in the future.
Landscape of gene transposition-duplication within the Brassicaceae family
Authors: Oh Dong-Ha , Dassanayake Maheshi 
Published: December 2017

ABSTRACTWe developed the CLfinder-OrthNet pipeline that detects co-linearity in gene arrangement among multiple closely related genomes; find ortholog groups; and encodes the evolutionary history of each ortholog group into a representative network (OrthNet). Using a search based on network topology, out of a total of 17,432 OrthNets in six Brassicaceae genomes, we identified 1,394 that included gene transposition-duplication (tr-d) events in one or more genomes. Occurrences of tr-d shared by subsets of Brassicaceae genomes mirrored the divergence times between the genomes and their repeat contents. The majority of tr-d events resulted in truncated open reading frames (ORFs) in the duplicated loci. However, the duplicates with complete ORFs were significantly more frequent than expected from random events. They also had a higher chance of being expressed and derived from older tr-d events. We also found an enrichment, compared to random chance, of tr-d events with complete loss of intergenic sequence conservation between the original and duplicated loci. Finally, we identified tr-d events uniquely found in two extremophytes among the six Brassicaceae genomes, including tr-d of SALT TOLERANCE 32 and ZINC TRANSPORTER 3. The CLfinder-OrthNet pipeline provides a flexible and a modular toolkit to compare gene order, encode and visualize evolutionary paths among orthologs as networks, and identify all gene loci that share the same evolutionary history using network topology searches.Funding source: This work was supported by National Science Foundation (MCB 1616827) and the Next Generation BioGreen21 Program (PJ011379) of the Rural Development Administration, Republic of Korea.Online-only Supplementary materials includes supplementary text (S1-S10), methods (M1-M4), figures (S1-S7), and tables (S1-S3), in two PDF files, one for text and methods and the other for figures and tables. Additionally, Supplementary Dataset S1 is available at the Figshare repository (https://doi.org/10.6084/m9.figshare.5825937) and Dataset S2 and S3 as separate Excel files.
Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis
Authors: Goodwin Leslie O. , Splinter Erik , Davis Tiffany L. , Urban Rachel , He Hao , Braun Robert E. , Chesler Elissa J. , Kumar Vivek , van Min Max , Ndukum Juliet , Philip Vivek M. , Reinholdt Laura G. , Svenson Karen , White Jacqueline K. , Sasner Michael , Lutz Cathleen , Murray Stephen A. 
Published: December 2017

ABSTRACTTransgenesis has been a mainstay of mouse genetics for over 30 years, providing numerous models of human disease and critical genetic tools in widespread use today. Generated through the random integration of DNA fragments into the host genome, transgenesis can lead to insertional mutagenesis if a coding gene or essential element is disrupted, and there is evidence that larger scale structural variation can accompany the integration. The insertion sites of only a tiny fraction of the thousands of transgenic lines in existence have been discovered and reported due in part to limitations in the discovery tools. Targeted Locus Amplification (TLA) provides a robust and efficient means to identify both the insertion site and content of transgenes through deep sequencing of genomic loci linked to specific known transgene cassettes. Here, we report the first large-scale analysis of transgene insertion sites from 40 highly used transgenic mouse lines. We show that the transgenes disrupt the coding sequence of endogenous genes in half of the lines, frequently involving large deletions and/or structural variations at the insertion site. Furthermore, we identify a number of unexpected sequences in some of the transgenes, including undocumented cassettes and contaminating DNA fragments. We demonstrate that these transgene insertions can have phenotypic consequences, which could confound certain experiments, emphasizing the need for careful attention to control strategies. Together, these data show that transgenic alleles display a high rate of potentially confounding genetic events, and highlight the need for careful characterization of each line to assure interpretable and reproducible experiments.
Anomalous Diffusion as a Descriptive Model of Cell Migration
Authors: Luzhanskey Igor D. , MacMunn John P. , Cohen Joshua D. , Barney Lauren E. , Jansen Lauren E. , Schwartz Alyssa D. , Peyton Shelly R. 
Published: December 2017

AbstractAppropriately chosen descriptive models of cell migration in biomaterials will allow researchers to characterize and ultimately predict the movement of cells in engineered systems for a variety of applications in tissue engineering. The persistent random walk (PRW) model accurately describes cell migration on two-dimensional (2D) substrates. However, this model inherently cannot describe subdiffusive cell movement, i.e. migration paths in which the root mean square displacement increases more slowly than the square root of the time interval. Subdiffusivity is a common characteristic of cells moving in confined environments, such as three-dimensional (3D) porous scaffolds, hydrogel networks, and in vivo tissues. We demonstrate that a generalized anomalous diffusion (AD) model, which uses a simple power law to relate the mean square displacement (MSD) to time, more accurately captures individual cell migration paths across a range of engineered 2D and 3D environments than does the more commonly used PRW model. We used the AD model parameters to distinguish cell movement profiles on substrates with different chemokinetic factors, geometries (2D vs 3D), substrate adhesivities, and compliances. Although the two models performed with equal precision for superdiffusive cells, we suggest a simple AD model, in lieu of PRW, to describe cell trajectories in populations with a significant subdiffusive fraction, such as cells in confined, 3D environments.
Decoupling from yolk sac is required for extraembryonic tissue spreading in the scuttle fly Megaselia abdita
Authors: Caroti Francesca , Avalos Everardo González , Noeske Viola , Avalos Paula González , Kromm Dimitri , Wosch Maike , Schütz Lucas , Hufnagel Lars , Lemke Steffen 
Published: December 2017

ABSTRACTExtraembryonic tissues contribute to animal development, which often entails spreading over embryo or yolk. Apart from changes in cell shape, the requirements for this tissue spreading are not well understood. Here we analyze spreading of the extraembryonic serosa in the scuttle fly Megaselia abdita. The serosa forms from a columnar blastoderm anlage, becomes a squamous epithelium, and eventually spreads over the embryo proper. We describe the dynamics of this process in long-term, whole-embryo time-lapse recordings, demonstrating that free serosa spreading is preceded by a prolonged pause in tissue expansion. Closer examination of this pause reveals mechanical coupling to the underlying yolk sac, which is later released. We find mechanical coupling prolonged and serosa spreading impaired after knockdown of M. abdita Matrix metalloprotease 1. We conclude that tissue-tissue interactions provide a critical functional element to constrain spreading epithelia.Impact StatementExtraembryonic tissue spreading in the scuttle fly Megaselia abdita requires mechanical decoupling from the underlying yolk sac.
Exploring FM’s dominant logics
Authors: Price Ilfryn 
Published: December 2017

Purpose
This paper aims to investigate the service ecosystem of facility/facilities management (FM) against the Vargo and Lusch framework of service-dominant logic (S-D Logic).

Design/methodology/approach
A theoretical argument guided by previous research into service excellence in FM.

Findings
In the paper, two arguments are made. First, FM is still dominated by a contractual logic grounded in the tangible world of buildings and bills of quantities. Second, the reciprocal flow of services inherent in the S-D Logic offers a powerful tool for appreciating real service excellence and a business contribution from FM.

Research limitations/implications
The S-D Logic framework is theoretical but, it is argued, has profound implications for the practical delivery of FM and the addition of both business and social value.

Originality/value
The reciprocal flow of service (as recognition, involvement and development) to FM’s “shop-floor” staff – the actual fee earners – may be the cornerstone of the co-creation and partnership, much espoused but less frequently practiced.
Failing to plan – planning to fail
Authors: Boge Knut , Salaj AlenkaTemeljotov , Bjørberg Svein , Larssen Anne Kathrine 
Published: December 2017

Purpose
The purpose of this paper is to know how do early-phase planning of real estate (RE) and facilities management (FM) create value for owners and users of commercial and public sector buildings.

Design/methodology/approach
The data were collected in Norway in 2015 through a national online survey (N = 837). The sample gives a good picture of Norwegian owners’ and even users on tactical-level (customer) perspectives on RE and FM. The data have been analysed through descriptive statistics and exploratory factor analysis. The hypotheses have been tested through analyses of correlations and ordinary least square (OLS) linear regressions.

Findings
Exploratory factor analysis made it possible to establish seven composite variables (constructs). Based on these seven constructs, six hypotheses were derived and tested. Obstacles and financials have no significant effect on buildings’ perceived usability. The most important factors during early-phase planning that influence buildings’ perceived usability and lifetime value creation are measures promoting environment and life-cycle costs (LCC), FM, adaptability and image.

Research limitations/implications
Further empirical and preferably, comparative studies are needed to establish whether the findings can be generalized. The study has shown that a building’s usability and lifetime value creation is largely determined by decisions made during early phase planning.

Practical implications
Well-founded early-phase planning of RE and FM may actually provide very high return on the investments and significantly improve the buildings’ lifetime value creation for owners and users. Early-phase planning is also of great importance both for buildings’ physical design, as well as for successful FM during the buildings’ use phase, and may prevent irreversible blunders.

Originality/value
This is a large N empirical study in Norway. The findings indicate what owner and users of buildings should emphasize during early phase planning.
Moderation effect on Islamic banking preferences in UAE
Authors: Warsame Mohammed Hersi , Ireri Edward Mugambi 
Published: December 2017

Purpose
The purpose of this paper is to examine the direct and indirect moderation effects of demographic and socio-economic(s) factors on the adoption of Islamic banking in UAE.

Design/methodology/approach
Convenience sampling was done on the residents of Sharjah, Dubai, and Abu Dhabi. A closed-ended questionnaire with 30 items was designed and pre-tested before the start of the study. Path analysis and moderation testing were the main analytical approach. A total of 320 respondents completed the survey.

Findings
The research revealed that demographic and socio-economic(s) moderators may have direct and indirect moderation effects on the adoption of the Islamic banking in the UAE, which indicates the importance of these factors in the provision of Islamic banking products and services in the UAE.

Practical implications
This study further revealed that these moderators have huge practical implications for Islamic bank managers and marketers as they can exploit these demographics to enhance their market share in the UAE.

Social implications
In UAE, minimal attention has been directed toward the role moderators would play in the criterion that individual investors would use in the adoption of Islamic banking products and services in a cosmopolitan environment that is experiencing competition from conventional banks.

Originality/value
An extensive review of the existing literature on the adoption of Islamic banking reveals that no empirical research has been undertaken to explore the role played by demographic and socio-economic(s) moderators in the adoption of Islamic banking in UAE and internationally. This study attempts to fill this gap.
Lessons from Thailand: universal healthcare achievements and challenges
Authors: Nonkhuntod Ravikan , Yu Suchuan 
Published: December 2017

Purpose
The purpose of this paper is to discuss the successes of Thailand’s healthcare system along with challenges it is facing, examining documents and policies used by those charged with developing and implementing health services.

Design/methodology/approach
The search pool comprised PubMed and Google Scholar from the period 2001-2015. Selection criterion for inclusion was sources dealing with out-of-pocket (OOP) expenditure and healthcare utilization in Thailand. In total, 33 studies met the criterion of containing sufficient data to be included in the meta-analysis.

Findings
The authors found a small positive effect size on OOP expenditure and healthcare utilization, obtaining values of 0.1604 (95% CI 0.1320-0.1888, p<0.0001) and 0.2788 (95% CI 0.0917-0.4659, p=0.0035), respectively.

Originality/value
To review and meta-analyze the literature dealing with the outcomes of Thailand’s healthcare system to understand whether Thailand’s healthcare system is achieving its mandate or not. The results of this paper can help policy makers to understand and evaluate Thailand’s healthcare system.
Explaining support for redistribution for different groups of the needy
Authors: Habibov Nazim , Cheung Chi Ho , Auchynnikava Alena 
Published: December 2017

Purpose
The purpose of this paper is to explore factors which may explain support for redistribution for different groups of the needy in 28 post-communist countries.

Design/methodology/approach
Using a cross-country survey (n=25,845), the authors evaluate preferences for redistribution to the elderly, the disabled, families with children, the working poor, and the unemployed.

Findings
People in post-communist countries made the distinction between deserving groups of the needy – the aged, the disabled, and families with children, and undeserving groups – the unemployed and the working poor. Among the individual-level factors, adherence to equality and attributing poverty to structural problems increased the probability of supporting redistribution. Among country-level factors, the authors’ results stress the positive influence of income inequality on support for redistribution for all groups of the needy under investigation. Notably, the authors did not find a negative influence of the business cycle on support for the working poor and unemployed.

Originality/value
This is the first paper that examines support for the needy in a diverse sample of 28 post-communist countries. The findings will help policy-makers and social administrators to better understand factors influencing support for redistribution toward different groups of the needy.