bluuebunny/crossref_metadata_2025_split huggingface dataset:
Likelihood analysis of population genetic data under coalescent models: computational and inferential aspects
Authors: Rousset François , Beeravolu Champak Reddy , Leblois Raphaël 
Published: September 2017

AbstractLikelihood methods are being developed for inference of migration rates and past demographic changes from population genetic data. We survey an approach for such inference using sequential importance sampling techniques derived from coalescent and diffusion theory. The consistent application and assessment of this approach has required the re-implementation of methods often considered in the context of computer experiments methods, in particular of Kriging which is used as a smoothing technique to infer a likelihood surface from likelihoods estimated in various parameter points, as well as reconsideration of methods for sampling the parameter space appropriately for such inference. We illustrate the performance and application of the whole tool chain on simulated and actual data, and highlight desirable developments in terms of data types and biological scenarios.RésuméDiverses approches ont été développées pour l’inférence des taux de migration et des changements démo-graphiques passés à partir de la variation génétique des populations. Nous décrivons une de ces approches utilisant des techniques d’échantillonnage pondéré séquentiel, fondées sur la modélisation par approches de coalescence et de diffusion de l’évolution de ces polymorphismes. L’application et l’évaluation systématique de cette approche ont requis la ré-implémentation de méthodes souvent considérées pour l’analyse de fonctions simulées, en particulier le krigeage, ici utilisé pour inférer une surface de vraisemblance à partir de vraisemblances estimées en différents points de l’espace des paramètres, ainsi que des techniques d’échantillonage de ces points. Nous illustrons la performance et l’application de cette série de méthodes sur données simulées et réelles, et indiquons les améliorations souhaitables en termes de types de données et de scénarios biologiques.Mots-cléshistoire démographique, processus de coalescence, importance sampling, genetic polymorphismAMS 2000 subject classifications92D10, 62M05, 65C05
Channel crosstalk correction in suspension and imaging mass cytometry
Authors: Chevrier Stéphane , Crowell Helena , Zanotelli Vito , Engler Stefanie , Robinson Mark D. , Bodenmiller Bernd 
Published: September 2017

ABSTRACTMass cytometry enables simultaneous analysis of over 40 proteins and their modifications in single cells through use of metal-tagged antibodies. Compared to fluorescent dyes, the use of pure metal isotopes strongly reduces spectral overlap among measurement channels. Crosstalk still exists, however, caused by isotopic impurity, oxide formation, and mass cytometer properties. Spillover effects can be minimized, but not avoided, by following a set of constraining rules when designing an antibody panel. Generation of such low crosstalk panels requires considerable expert knowledge, knowledge of the abundance of each marker and substantial experimental effort. Here we describe a novel bead-based compensation workflow that includes R-based software and a web tool, which enables correction for interference between channels. We demonstrate utility in suspension mass cytometry and show how this approach can be applied to imaging mass cytometry. Our approach greatly simplifies the development of new antibody panels, increases flexibility for antibody-metal pairing, improves overall data quality, thereby reducing the risk of reporting cell phenotype and function artifacts, and greatly facilitates analysis of complex samples for which antigen abundances are unknown.
Modeling Marek’s disease virus transmission: a framework for evaluating the impact of farming practices and evolution on disease
Authors: Kennedy David A. , Dunn Patricia A. , Read Andrew F. 
Published: September 2017

AbstractMarek’s disease virus (MDV) is a pathogen of chickens whose control has twice been un-dermined by pathogen evolution. Disease ecology is believed to be the main driver of this evolution, yet mathematical models of MDV disease ecology have never been confronted with data to test their reliability. Here, we develop a suite of MDV models that differ in the ecological mechanisms they include. We fit these models with maximum likelihood in ‘pomp’ to data on MDV concentration in dust collected from two commercial broiler farms. Using AIC to compare the models, we find that virus dynamics are influenced by between-flock variation in host susceptibility to virus, shedding rate from infected birds, and cleanout efficiency. We also find evidence that virus is reintroduced to farms approximately once per month, but we do not find evidence that virus sanitization rates vary between flocks. Of the models that survive model selection, we find agreement between parameter estimates and previous experimental data, as well as agreement between field data and the predictions of these models, suggesting robustness of model predictions. Using the set of surviving models, we explore how changes to farming practices are predicted to influence MDV costs, should pathogen evolution undermine existing control measures. By quantitatively capturing the mechanisms of disease ecology, we have laid the groundwork to explore the future trajectory of virus evolution.
mosdepth: quick coverage calculation for genomes and exomes
Authors: Pedersen Brent S. , Quinlan Aaron R. 
Published: September 2017

AbstractMosdepthis a new command-line tool for rapidly calculating genome-wide sequencing coverage. It measures depth from BAM (Li et al. 2009) or CRAM files at either each nucleotide position in a genome or for sets of genomic regions. Genomic regions may be specified as either a BED file to evaluate coverage across capture regions, or as a fixed-size window as required for copy-number calling. Mosdepth uses a simple algorithm that is computationally efficient and enables it to quickly produce optional coverage summaries. We demonstrate thatmosdepthis faster than existing tools and provides flexibility in the types of coverage profiles produced.Availabilitymosdepthis available fromhttps://github.com/brentp/mosdepthunder the MIT license‥Contactbpederse@gmail.com,aaronquinlan@gmail.comSupplementary informationDetailed documentation is available athttps://github.com/brentp/mosdepth
Complemented palindrome small RNAs first discovered from SARS coronavirus
Authors: Liu Chang , Chen Ze , Shen Wenyuan , Yu Deshui , Li Siyu , Hu Yue , Ji Haishuo , Bu Wenjun , Wang Qingsong , Gao Shan 
Published: September 2017

AbstractIn this study, we reported for the first time the existence of complemented palindrome small RNAs (cpsRNAs) and proposed cpsRNAs and palindrome small RNAs (psRNAs) as a novel class of small RNAs. The first discovered cpsRNA UCUUUAACAAGCUUGUUAAAGAfrom SARS coronavirus named SARS-CoV-cpsR-22 contained 22 nucleotides perfectly matching its reverse complementary sequence. Further sequence analysis supported that SARS-CoV-cpsR-22 originated from bat betacoronavirus. The results of RNAi experiments showed that one 19-nt segment of SARS-CoV-cpsR-22 significantly induced cell apoptosis. These results suggested that SARS-CoV-cpsR-22 could play a role in SARS-CoV infection or pathogenicity. The discovery of psRNAs and cpsRNAs paved the way to find new markers for pathogen detection and reveal the mechanisms in the infection or pathogenicity from a different point of view. The discovery of psRNAs and cpsRNAs also broaden the understanding of palindrome motifs in animal of plant genomes.
Antibiotic collateral sensitivity is contingent on the repeatability of evolution
Authors: Nichol Daniel , Rutter Joseph , Bryant Christopher , Hujer Andrea M , Lek Sai , Adams Mark D , Jeavons Peter , Anderson Alexander RA , Bonomo Robert A , Scott Jacob G 
Published: September 2017

AbstractAntibiotic resistance represents a growing health crisis that necessitates the immediate discovery of novel treatment strategies. One such strategy is the identification of collateral sensitivities, wherein evolution under a first drug induces susceptibility to a second. Here, we report that sequential drug regimens derived fromin vitroevolution experiments may have overstated therapeutic benefit, predicting a collaterally sensitive response where cross resistance ultimately occurs. We quantify the likelihood of this phenomenon by use of a mathematical model parametrised with combinatorially complete fitness landscapes forEscherichia coli. Through experimental evolution we then verify that a second drug can indeed stochastically exhibit either increased susceptibility or increased resistance when following a first. Genetic divergence is confirmed as the driver of this differential response through targeted and whole genome sequencing. Taken together, these results highlight that the success of evolutionarily-informed therapies is predicated on a rigorous probabilistic understanding of the contingencies that arise during the evolution of drug resistance.
Universal Transcriptional Responses to Different Modalities of Traumatic Stress as a Measure of Stress Exposure
Authors: Jacobson Moriah L. , Kim Lydia A. , Rosati Barbara , McKinnon David 
Published: September 2017

AbstractMolecular diagnostic tools that can robustly and quantitatively measure the response to traumatic stress would be of considerable value in assessing the individual risk of developing post-traumatic stress disorder or stress-induced depression following stress exposure. The gene regulatory network can integrate and encode a large number of different signals, including those elicited by exposure to stress. We find that many genes respond to at least one modality of stress but only a subset of stress-sensitive genes track stress exposure across multiple stress modalities and are thus universal markers of stress exposure. A sensitive and robust measure of stress exposure can be constructed using a small number of genes selected from this modality-independent set of stress-sensitive genes. This stress-sensitive gene expression (SSGE) index can detect chronic traumatic stress exposure in a wide range of different stress models in a manner that is relatively independent of the modality of stress exposure and that parallels the intensity of stress exposure in a dose-dependent manner.
HiCTMap: Detection and Analysis of Chromosome Territory Structure and Position by High-throughput Imaging
Authors: Jowhar Ziad , Gudla Prabhakar , Shachar Sigal , Wangsa Darawalee , Russ Jill L. , Pegoraro Gianluca , Ried Thomas , Raznahan Armin , Misteli Tom 
Published: September 2017

AbstractThe spatial organization of chromosomes in the nuclear space is an extensively studied field that relies on measurements of structural features and 3D positions of chromosomes with high precision and robustness. However, no tools are currently available to image and analyze chromosome territories in a high-throughput format. Here, we have developed High-throughput Chromosome Territory Mapping (HiCTMap), a method for the robust and rapid analysis of 2D and 3D chromosome territory positioning in mammalian cells. HiCTMap is a high-throughput imaging-based chromosome detection method which enables routine analysis of chromosome structure and nuclear position. Using an optimized FISH staining protocol in a 384-well plate format in conjunction with a bespoke automated image analysis workflow, HiCTMap faithfully detects chromosome territories and their position in 2D and 3D in a large population of cells per experimental condition. We apply this novel technique to visualize chromosomes 18, X, and Y in male and female primary human skin fibroblasts, and show accurate detection of the correct number of chromosomes in the respective genotypes. Given the ability to visualize and quantitatively analyze large numbers of nuclei, we use HiCTMap to measure chromosome territory area and volume with high precision and determine the radial position of chromosome territories using either centroid or equidistant-shell analysis. The HiCTMap protocol is also compatible with RNA FISH as demonstrated by simultaneous labeling of X chromosomes andXistRNA in female cells. We suggest HiCTMap will be a useful tool for routine precision mapping of chromosome territories in a wide range of cell types and tissues.
Chromatin run-on reveals the transcriptional etiology of glioblastoma multiforme
Authors: Chu Tinyi , Rice Edward J. , Booth Gregory T. , Salamanca H. Hans , Wang Zhong , Core Leighton J. , Longo Sharon L. , Corona Robert J. , Chin Lawrence S. , Lis John T. , Kwak Hojoong , Danko Charles G. 
Published: September 2017

AbstractThe human genome encodes a variety of poorly understood RNA species that remain challenging to identify using existing genomic tools. We developed chromatin run-on and sequencing (ChRO-seq) to map the location of RNA polymerase using virtually any input sample, including samples with degraded RNA that are intractable to conventional RNA-seq. We used ChRO-seq to develop the first maps of nascent transcription in primary human glioblastoma (GBM) brain tumors. Whereas enhancers discovered in primary GBMs resemble open chromatin in the normal human brain, rare enhancers activated in malignant tissue drive regulatory programs similar to the developing nervous system. We identified enhancers that regulate genes characteristic of each known GBM subtype, identified transcription factors that drive them, and discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study uncovers new insights into the molecular etiology of GBM and introduces ChRO-seq which can now be used to map regulatory programs contributing to a variety of complex diseases.
Inter-areal balanced amplification enhances signal propagation in a large-scale circuit model of the primate cortex
Authors: Joglekar Madhura R. , Mejias Jorge F. , Yang Guangyu Robert , Wang Xiao-Jing 
Published: September 2017

AbstractReliable signal transmission represents a fundamental challenge for cortical systems, which display a wide range of weights of feedforward and feedback connections among heterogeneous areas. We re-examine the question of signal transmission across the cortex in network models based on recently available mesoscopic, directed‐ and weighted-inter-areal connectivity data of the macaque cortex. Our findings reveal that, in contrast to feed-forward propagation models, the presence of long-range excitatory feedback projections could compromise stable signal propagation. Using population rate models as well as a spiking network model, we find that effective signal propagation can be accomplished by balanced amplification across cortical areas while ensuring dynamical stability. Moreover, the activation of prefrontal cortex in our model requires the input strength to exceed a threshold, in support of the ignition model of conscious processing, demonstrating our model as an anatomically-realistic platform for investigations of the global primate cortex dynamics.
Src42A required for collective border cell migrationin vivo
Authors: Sallak Yasmin , Torres Alba Yurani , Yin Hongyan , Montell Denise 
Published: September 2017

AbstractThe tyrosine kinase Src is over-expressed in numerous human cancers and is associated with poor prognosis. While Src has been extensively studied, its contributions to collective cell migrationin vivoremain incompletely understood. Here we show that Src42A, but not Src64, is required for the specification and migration of the border cells in the Drosophila ovary, a well-developed and genetically tractablein vivocell migration model. We found active Src42A enriched at border cell/nurse cell interfaces, where E-cadherin is less abundant, and depleted from border cell/border cell and border cell/polar cell junctions where E-cadherin is more stable, whereas total Src42A protein co-localizes with E-cadherin. Over-expression of wild type Src42A mislocalized Src activity and prevented border cell migration. Constitutively active or kinase dead forms of Src42A also impeded border cells. These findings establish border cells as a model for investigating the mechanisms of action of Src in cooperative, collective, cell-on-cell migrationin vivo.
Expecting “the Arab world”: imaginative geographies as dominant diversity frames
Authors: Mahadevan Jasmin , Kilian-Yasin Katharina , Ilie Iuliana Ancuţa , Müller Franziska 
Published: September 2017

PurposeThe purpose of this paper is to highlight the dangers of Orientalist framing. Orientalism (Said, 1979/2003) shows how “the West” actually creates “the Orient” as an inferior opposite to affirm itself, for instance by using imaginative geographical frames such as “East” and “West” (Said, 1993).Design/methodology/approachQualitative interviews were conducted with the members of a German-Tunisian project team in research engineering. The interview purpose was to let individuals reflect upon their experiences of difference and to find out whether these experiences are preframed by imaginative geographical categories.FindingsTunisian researchers were subjected to the dominant imaginative geographical frame “the Arab world.” This frame involves ascribed religiousness, gender stereotyping and ascriptions of backwardness.Research limitations/implicationsResearch needs to investigate Orientalist thought and imaginative geographies in specific organizational and interpersonal interactions lest they overshadow managerial theory and practice.Practical implicationsPractitioners need to challenge dominant frames and Orientalist thought in their own practice and organizational surroundings to devise a truly inclusive managerial practice, for instance, regarding Muslim minorities.Social implicationsIn times of Islamophobia and anti-Muslim sentiment in “the West,” this paper highlights the frames from which such sentiments might originate, and the need to reflect upon them.Originality/valueThe theoretical value lies in introducing a critical framing approach and the concept of imaginative geographies to perceived differences at work. For practice, it highlights how certain individuals are constructed as “Muslim others” and subjected to ascriptions of negative difference. By this mechanism, their inclusion is obstructed.
Implementing the living wage in UK local government
Authors: Johnson Mathew 
Published: September 2017

PurposeThe purpose of this paper is to understand the impact of living wages on organisational pay systems.Design/methodology/approachThe research draws on 23 semi-structured interviews with HR managers, trade union representatives, and politicians at four UK local government case study sites.FindingsThe findings suggest that living wages can have a positive impact on directly employed workers in cleaning, catering and care services, but the research also finds that the localised adoption of living wages can lead to significant wage compression, resulting in a broad band of “low skill-low wage jobs”.Originality/valueThe theoretical contribution is twofold. In-line with earlier research the “first-order” effects of living wages are clear: hourly wages for a large number of women in part-time roles increased sharply. However, this is only part of the story as “second-order” effects such as ripples and spill-overs are less extensive than suggested by other studies. This is due to the limited scope for trade unions to restore wage differentials through collective bargaining, the slow progress in extending the living wage to contracted staff, and parallel processes of downsizing and outsourcing.
The toxic politicising of the National Minimum Wage
Authors: Brown William 
Published: September 2017

Purpose
After 15 years of successful operation, the British Low Pay Commission’s management of the National Minimum Wage was threatened in 2015 by the government’s introduction the National Living Wage. The purpose of this paper is to consider the underlying principles of previous minimum wage fixing, and the additional thinking of the Living Wage Foundation and the review of the issue by the Resolution Foundation.

Design/methodology/approach
The paper draws on the 2016 reports of the Commission to argue that the two statutory wages are unavoidably interlinked and are tied to incompatible criteria.

Findings
The paper concludes that the predicted eventual impact of the National Living Wage on the labour market will be unsustainable.

Research limitations/implications
The paper is relevant to minimum wage research.

Practical implications
The paper is relevant to minimum wage policy.

Social implications
The paper is relevant to low pay policy.

Originality/value
The paper provides original analysis of minimum wage policy.
The UK living wage
Authors: Sellers Paul John 
Published: September 2017

Purpose
The purpose of this paper is to explore the value that UK trade unions now place on the living wage.

Design/methodology/approach
The author is the TUC’s Pay Policy Officer and examines the issue from a practitioner’s perspective.

Findings
The living wage now has a well-established place within the hierarchy of pay demands adopted by UK trade unions. This continues a tradition of unions supporting norms and regulations as an adjunct to collective bargaining. However, support had to be achieved through a process of negotiation with the broader UK living wage campaign.

Practical implications
The paper concludes that there are good prospects for the living wage, and thus for the continued trade union support.

Social implications
The living wage standard is seen as having a strong moral basis, which often helps to win agreement with good employers. This results in a steady stream of workers out of in-work poverty. The credit for such pay increases is often shared between employers and trade unions.

Originality/value
The paper is written by a practitioner with inside knowledge and experience of the entire course of the living wage campaign in the UK and how it has been adopted and integrated by trade unions.
Sexual coercion, sexual aggression, or sexual assault: how measurement impacts our understanding of sexual violence
Authors: Bouffard Leana , Goodson Amanda 
Published: September 2017

Purpose
Definitions of rape and sexual aggression have varied widely in the research literature, resulting in a wide range of estimates for perpetration and remaining questions as to the factors that may affect involvement in sexual violence. The paper aims to discuss this issue.

Design/methodology/approach
The current study uses a sample of college men to assess multiple forms of measurement of sexual aggression and theoretical predictors.

Findings
Findings indicate that the different measures of sexual aggression (broad vs narrow; hypothetical vs behavioral) are significantly correlated with each other. Additionally, many theoretical predictors (rape myths, low self-control, sexual entitlement, and pornography use) are consistently related to all measurement forms. However, some variables (masculinity, peer support for violence against women, sexual partners, and alcohol and drug use) are only related to broad measures of sexual aggression, and some are related only to hypothetical (i.e. certainty of apprehension) or behavioral measures (i.e. fraternity membership).

Research limitations/implications
Because of the chosen approach, the results may lack generalizability. Findings do, however, point to important considerations in defining sexual aggression moving forward.

Practical implications
Results point to the importance of aiming policy and programs at the particular characteristics that most consistently impact sexual aggression.

Originality/value
This paper addresses lingering questions about the impact of differences in definition and measurement on understanding sexual aggression.