bluuebunny/crossref_metadata_2025_split huggingface dataset:
Joint analysis of matched tumor samples with varying tumor contents improves somatic variant calling in the absence of a germline sample
Authors: Halperin Rebecca F. , Liang Winnie S. , Kulkarni Sidharth , Tassone Erica E. , Adkins Jonathan , Enriquez Daniel , Tran Nhan L. , Hank Nicole C. , Newell James , Kodira Chinnappa , Korn Ronald , Berens Michael E. , Kim Seungchan , Byron Sara A. 
Published: July 2018

AbstractArchival tumor samples represent a potential rich resource of annotated specimens for translational genomics research. However, standard variant calling approaches require a matched normal sample from the same individual, which is often not available in the retrospective setting, making it difficult to distinguish between true somatic variants and germline variants that are private to the individual. Archival sections often contain adjacent normal tissue, but this normal tissue can include infiltrating tumor cells. Comparative somatic variant callers are designed to exclude variants present in the normal sample, so a novel approach is required to leverage sequencing of adjacent normal tissue for somatic variant calling. Here we present LumosVar 2.0, a software package designed to jointly analyze multiple samples from the same patient. The approach is based on the concept that the allelic fraction of somatic variants, but not germline variants, would be reduced in samples with low tumor content. LumosVar 2.0 estimates allele specific copy number and tumor sample fractions from the data, and uses the model to determine expected allelic fractions for somatic and germline variants and classify variants accordingly. To evaluate using LumosVar 2.0 to jointly call somatic variants with tumor and adjacent normal samples, we used a glioblastoma dataset with matched high tumor content, low tumor content, and germline exome sequencing data (to define true somatic variants) available for each patient. We show that both sensitivity and positive predictive value are improved by analyzing the high tumor and low tumor samples jointly compared to analyzing the samples individually or compared to in-silico pooling of the two samples. Finally, we applied this approach to a set of breast and prostate archival tumor samples for which normal samples were not available for germline sequencing, but tumor blocks containing adjacent normal tissue were available for sequencing. Joint analysis using LumosVar 2.0 detected several variants, including known cancer hotspot mutations that were not detected by standard somatic variant calling tools using the adjacent normal as a reference. Together, these results demonstrate the potential utility of leveraging paired tissue samples to improve somatic variant calling when a constitutional DNA sample is not available.
Multi-scale deep tensor factorization learns a latent representation of the human epigenome
Authors: Schreiber Jacob , Durham Timothy , Bilmes Jeffrey , Noble William Stafford 
Published: July 2018

AbstractThe human epigenome has been experimentally characterized by measurements of protein binding, chromatin acessibility, methylation, and histone modification in hundreds of cell types. The result is a huge compendium of data, consisting of thousands of measurements for every basepair in the human genome. These data are difficult to make sense of, not only for humans, but also for computational methods that aim to detect genes and other functional elements, predict gene expression, characterize polymorphisms, etc. To address this challenge, we propose a deep neural network tensor factorization method, Avocado, that compresses epigenomic data into a dense, information-rich representation of the human genome. We use data from the Roadmap Epigenomics Consortium to demonstrate that this learned representation of the genome is broadly useful: first, by imputing epigenomic data more accurately than previous methods, and second, by showing that machine learning models that exploit this representation outperform those trained directly on epigenomic data on a variety of genomics tasks. These tasks include predicting gene expression, promoter-enhancer interactions, replication timing, and an element of 3D chromatin architecture. Our findings suggest the broad utility of Avocado’s learned latent representation for computational genomics and epigenomics.
Sexually dimorphic recombination can facilitate the establishment of sexually antagonistic polymorphisms in guppies
Authors: Bergero Roberta , Gardner Jim , Bader Beth , Yong Lengxob , Charlesworth Deborah 
Published: July 2018

Summary/AbstractRecombination suppression between sex chromosomes is often stated to evolve in response to polymorphisms for mutations that affect fitness of males and females in opposite directions (sexually antagonistic, or SA, mutations), but direct empirical support is lacking. The sex chromosomes of the fishPoecilia reticulata(the guppy) carry SA polymorphisms, making them excellent for testing this hypothesis for the evolution of sex linkage. We resequenced genomes of male and female guppies and, unexpectedly, found that variants on the sex chromosome indicate no extensive region with fully sex-linked genotypes, though many variants show strong evidence for partial sex linkage. We present genetic mapping results that help understand the evolution of the guppy sex chromosome pair. We find very different distributions of crossing over in the two sexes, with recombination events in male meiosis detected only at the tips of the chromosomes. The guppy may exemplify a route for sex chromosome evolution in which low recombination in males, likely evolved in a common ancestor, has facilitated the establishment of sexually antagonistic polymorphisms.
Impact of acetolactate synthase inactivation on 1,3-propanediol fermentation byKlebsiella pneumoniae
Authors: Zhou Sheng , Huang Youhua , Mao Xinliang , Li Lili , Guo Chuanyu , Gao Yongli , Qin Qiwei 
Published: July 2018

Abstract1,3-Propanediol (1,3-PDO) is an important compound that is mainly used in industry for polymer production. Fermentation of 1,3-PDO from glycerol by marineKlebsiella pneumoniaeis accompanied by formation of 2,3-butanediol (2,3-BDO) as one of the main byproduct. The first step in the formation of 2,3-BDO from pyruvate is catalyzed by acetolactate synthase (ALS), an enzyme that competes with 1,3-PDO oxidoreductase for the cofactor NADH. This study aimed to analyze the impact of engineering the 2,3-BDO formation pathway via inactivation of ALS on 1,3-PDO fermentation by marineK. pneumoniaeHSL4. An ALS mutant was generated using Red recombinase assisted gene replacement. The ALS specific activities ofK. pneumoniaeΔALS were notably lower than that of the wild-type strain. Fed-batch fermentation of the mutant strain resulted in a 1,3-PDO concentration, productivity and conversion of 72.04 g L−1, 2.25 g L−1h−1, and 0.41 g g−1, a slightly increase compared with the parent strain. Moreover, inactivation of ALS decreasedmeso-2,3-BDO formation to trace amounts, significantly increased 2S,3S-BDO and lactate production, and a pronounced redistribution of intracellular metabolic flux was apparent.
Autism-associated Shank3 is essential for homeostatic plasticity and neuronal circuit stability
Authors: Tatavarty Vedakumar , Pacheco Alejandro Torrado , Lin Heather , Miska Nathaniel J. , Hengen Keith B. , Wagner Florence F. , Turrigiano Gina G. 
Published: July 2018

SummaryMutations in Shank3 are strongly associated with autism spectrum disorders and circuit disfunction, but a unified view of how Shank3 loss disrupts circuit function and excitability is lacking. Stabilizing, homeostatic forms of synaptic and intrinsic plasticity are critical for preventing circuit hyper- or hypo-excitability, leading us to ask whether Shank3 loss perturbs circuits by disrupting homeostatic plasticity. We show that Shank3 loss abolishes synaptic and intrinsic homeostatic plasticity, which can be rescued by lithium(Li), a drug with therapeutic potential in human Shankopathies. Further, Shank3 loss in vivo severely compromises the ability of visual cortical circuits to recover from perturbations to sensory drive. Our findings suggest that the loss of homeostatic compensation is a critical endophenotype that can explain a range of circuit disfunctions in Shankopathies.
Estimating recent migration and population size surfaces
Authors: Al-Asadi Hussein , Petkova Desislava , Stephens Matthew , Novembre John 
Published: July 2018

AbstractIn many species a fundamental feature of genetic diversity is that genetic similarity decays with geographic distance; however, this relationship is often complex, and may vary across space and time. Methods to uncover and visualize such relationships have widespread use for analyses in molecular ecology, conservation genetics, evolutionary genetics, and human genetics. While several frameworks exist, a promising approach is to infer maps of how migration rates vary across geographic space. Such maps could, in principle, be estimated across time to reveal the full complexity of population histories. Here, we take a step in this direction: we present a method to infer separate maps of population sizes and migration rates for different time periods from a matrix of genetic similarity between every pair of individuals. Specifically, genetic similarity is measured by counting the number of long segments of haplotype sharing (also known as identity-by-descent tracts). By varying the length of these segments we obtain parameter estimates for qualitatively different time periods. Using simulations, we show that the method can reveal time-varying migration rates and population sizes, including changes that are not detectable when ignoring haplotypic structure. We apply the method to a dataset of contemporary European individuals (POPRES), and provide an integrated analysis of recent population structure and growth over the last~3,000 years in Europe. Software implementing the methods is available athttps://github.com/halasadi/MAPS.
The first genetic linkage map forFraxinus pennsylvanicaand syntenic relationships with four related species
Authors: Wu Di , Koch Jennifer , Coggeshall Mark , Carlson John 
Published: July 2018

AbstractGreen ash (Fraxinus pennsylvanica) is an outcrossing, diploid (2n=46) hardwood tree species, native to North America. Native ash species in North America are being threatened by the rapid invasion of emerald ash borer (EAB,Agrilus planipennis) from Asia. Green ash, the most widely distributed ash species, is severely affected by EAB infestation, yet few resources for genetic studies and improvement of green ash are available. In this study, a total of 5,712 high quality single nucleotide polymorphisms (SNPs) were discovered using a minimum allele frequency of 1% across the entire genome through genotyping-by-sequencing. We also screened hundreds of genomic- and EST-based microsatellite markers (SSRs) from previousde novoassemblies (Staton et al. 2015; Lane et al. 2016). A first genetic linkage map of green ash was constructed from 91 individuals in a full-sib family, combining 2,719 SNP and 84 SSR segregating markers among the parental maps. The consensus SNP and SSR map contains a total of 1,201 markers in 23 linkage groups spanning 2008.87cM, at an average inter-marker distance of 1.67 cM with a minimum logarithm of odds (LOD) of 6 and maximum recombination fraction of 0.40. Comparisons of the organization the green ash map with the genomes of asterid species coffee and tomato, and genomes of the rosid species poplar and peach, showed areas of conserved gene order, with overall synteny strongest with coffee.
Phosphatidic acid inhibits SNARE priming by inducing conformational changes in Sec18 protomers
Authors: Starr Matthew L. , Sparks Robert P. , Hurst Logan R. , Zhao Zhiyu , Arango Andres , Lihan Muyun , Jenkins Jermaine L. , Tajkhorshid Emad , Fratti Rutilio A. 
Published: July 2018

SUMMARYEukaryotic homeostasis relies on membrane fusion catalyzed by SNARE proteins. Inactive SNARE bundles are re-activated by Sec18/NSF driven disassembly to enable a new round of fusion. We previously found that phosphatidic acid (PA) binds Sec18 to sequester it from SNAREs. Dephosphorylation of PA dissociates Sec18 from the membrane allowing it to engage SNARE complexes. We now report that PA induces conformational changes in Sec18 protomers, while hexameric Sec18 cannot bind PA membranes. The association of Sec18 with PA was shown to be sensitive to membrane curvature, suggesting that regulation could vary on different organelles in a curvature dependent manner. Molecular dynamics showed that PA binding sites exist on the D1 and D2 domains of Sec18 and that residues needed for binding were masked in the hexameric form of the protein. Together these data indicate that PA regulates Sec18 function through altering protein architecture and stabilizing membrane-bound protomers.
Supplier transparency: scale development and validation
Authors: Morgan Tyler R. , Richey Jr Robert Glenn , Ellinger Alexander E. 
Published: July 2018

PurposeThe purpose of this paper is to create an instrument for conducting future supply chain transparency research by developing and validating a measure of supplier transparency. Specifically, the research develops a two-dimensional measure of supplier transparency that builds on previous studies that independently examine visibility and traceability in supply chain management (SCM)/logistics.Design/methodology/approachThe scale development process is carried out over three stages (item generation, scale purification, scale validation). Survey methods are used with two separate data collection phases involving a total of 358 managers from multiple and diverse industries.FindingsThe new supplier transparency measure is a concise, two-dimensional scale that has the potential for significant usage in the development and testing of SCM theory.Research limitations/implicationsThis study implemented a purposefully general sampling procedure. However, different industries may have additional, specific constraints regarding what it means to be a transparent supplier. Additional opportunities for future research include applying the new supplier transparency measure to examine supply chain frameworks, regulatory compliance, supply chain relationships and the implementation of information technology.Practical implicationsFirms are under increasing pressure to be transparent about partner sourcing, resource utilization and other transactional issues related to the products and processes in their supply chains. The new measure may be utilized to address these issues as well as the interaction between supply chain operations and stakeholders by facilitating a quantitative assessment of supplier transparency.Originality/valueDrawing on the established constructs of supply chain visibility and traceability, a measure of supplier transparency is developed, supported by a review of the literature, input from subject matter experts and interviews with supply chain managers. Suggestions are made for future validation of supplier transparency within established supply chain frameworks.
A systematic approach to root cause analysis using 3 × 5 why’s technique
Authors: Gangidi Prashant 
Published: July 2018

Purpose
The purpose of this paper is to go a step further from the traditional 5 Whys technique by adding three more legs during the root cause analysis stage – occurrence, human and systemic issues that contribute toward the problem, hence the term 3 × 5 Whys. Performing individual 5 Whys for these three components enables to identify deeper root cause(s) that may spawn across multiple groups within an organization.

Design/methodology/approach
Cause-and-effect analysis used during traditional root cause investigations within an 8D or Lean six sigma project is used as a theoretical foundation. Examples from different industries are presented showing the 3 × 5 Why’s framework and advantages it brings to the organization along with identifying shortcomings and suggestions to make it more effective.

Findings
If properly used this integrated methodology will reveal higher order systemic causes (e.g. policies or management decisions) stemming from lower lever symptoms (e.g. defective parts, procedural errors). Effective execution of this methodology can provide tremendous results in defect reduction, yield improvement, operational efficiency improvement and logistics management type of projects. Resolving higher level sources of problems allows an organization to evolve itself and maintain a competitive edge in the market.

Research limitations/implications
Adopting this quality management technique in start-up companies entails some challenges and other implications have been discussed with SWOT analysis.

Practical implications
Examples from various sectors using 3 × 5 Why approach have been presented that show that this methodology provides deeper insight into root causes which could be affecting multiple groups in an organization. Using this technique effectively is found to be beneficial to resolve issues in operations management, logistics, supply chain, purchasing, warehouse operations, manufacturing, etc.

Social implications
This methodology has a human component which often results in some sort of resistance as not all working professionals think alike when it comes to accountability and ownership of issues. This may hinder root cause analysis and subsequent corrective actions implementation.

Originality/value
This study is unique in its in-depth real-world case studies demonstrating the need for taking a deep dive approach to root cause analysis by understanding specific, system and human components responsible for causing the failure mode.
A simplified analytical method for the pressure of tilt hydrostatic journal bearing
Authors: Du Yikang , Mao Kuanmin , Liu Hongqi , Mao Xiaobo , Li Zhihang 
Published: July 2018

Purpose
This paper aims to present a simplified method to predict the pressure of the recess, no matter whether the tilt center coincides with the geometric center of the hydrostatic journal bearings.

Design/methodology/approach
To validate the effectiveness of the presented model, computational fluid dynamics (CFD) method and experimental method are performed in this study.

Findings
By comparing the CFD results and the experimental results, the pressure of the recess is related to the tilt direction, the tilt center, the width of the land and the circumferential angle of the land.

Originality/value
The mathematic model requires equivalent resistance of land edge – tilt position, tilt direction, tilt angle and the thickness of oil film instead of any digital iteration. Furthermore, a novel experimental apparatus including a circular hydrostatic bearing called ball bearing is designed to study the tilt effect produced by manufacturing error and offset load force on the pressure of the recess.
Some basic observations on conducting a systematic review: a brief reply to Goldstein, Vatalaro and Yair
Authors: See Beng Huat , Gorard Stephen 
Published: July 2018

Purpose
The purpose of this paper is to provide a response to Goldstein et al.’s (2017) attempted rebuttal of the authors’ prior paper in this journal (See and Gorard 2015).

Design/methodology/approach
The prior paper reported a systematic review of interventions to involve engaging parents more in their children’s education in order to raise school attainment. Goldstein et al. make a large number of unwarranted claims about its quality. They reproach the authors for using reports of unpublished evidence, for mis-labelling or mis-describing studies, and for denigrating studies by labelling them as “bad”. The authors were very surprised when first alerted to this response and went back to look at all of the research reports that Goldstein et al. claimed the authors mis-represented in the authors’ assessment.

Findings
The authors found that the Goldstein et al. claims are false and based on such a poor understanding of how evidence is reviewed that it was strange to see their paper in this journal.

Originality/value
In the authors’ reply, they look first at why unpublished material must be included in a review, and why the outlet for publication is not relevant, then at appropriate designs for causal questions, and at the confusion in Goldstein et al. between evaluation quality and intervention impact. The authors look at many examples where the confusion leads to Goldstein et al. making incorrect assertions about the authors’ paper, in order to make the point that their whole idea of how to conduct a systematic review is wrong.
Real estate media sentiment through textual analysis
Authors: Ruscheinsky Jessica Roxanne , Lang Marcel , Schäfers Wolfgang 
Published: July 2018

Purpose
The purpose of this paper is to determine systematically the broader relationship between news media sentiment, extracted through textual analysis of articles published by leading US newspapers, and the securitized real estate market.

Design/methodology/approach
The methodology is divided into two stages. First, roughly 125,000 US newspaper article headlines from Bloomberg, The Financial Times, Forbes and The Wall Street Journal are investigated with a dictionary-based approach, and different measures of sentiment are created. Second, a vector autoregressive framework is used to analyse the relationship between media-expressed sentiment and REIT market movements over the period 2005–2015.

Findings
The empirical results provide significant evidence for a leading relationship between media sentiment and future REIT market movements. Furthermore, applying the dictionary-based approach for textual analysis, the results exhibit that a domain-specific dictionary is superior to a general dictionary. In addition, better results are achieved by a sentiment measure incorporating both positive and negative sentiment, rather than just one polarity.

Practical implications
In connection with fundamentals of the REIT market, these findings can be utilised to further improve the understanding of securitized real estate market movements and investment decisions. Furthermore, this paper highlights the importance of paying attention to new media and digitalization. The results are robust for different REIT sectors and when conventional control variables are considered.

Originality/value
This paper demonstrates for the first time, that textual analysis is able to capture media sentiment from news relevant to the US securitized real estate market. Furthermore, the broad collection of newspaper articles from four different sources is unique.
Modulatory effect of intravenous immunoglobulin on Th17/Treg cell balance in women with unexplained recurrent spontaneous abortion
Authors: Muyayalo Kahinho P. , Li Zhi‐Hui , Mor Gil , Liao Ai‐Hua 
Published: July 2018

AbstractRecurrent spontaneous abortion (RSA) is a growing problem worldwide. In a majority of cases, the cause remains unknown but there is increasing evidence that immunologic factors play an important role. Intravenous immunoglobulin (IVIg) therapy has been proposed to have immune modulatory effects and therefore been applicable for the treatment of patients with RSA. Although its efficacy is still controversial, several recent studies suggest that IVIg treatment may improve pregnancy outcomes. CD4+ T cells and their related cytokines play an important role in maternal‐fetal immune regulation, and an imbalance of Th17/Treg cell ratio has been proposed as a cause for RSA. We review the scientific evidence supporting a modulatory effect of IVIg on Th17/Treg cell balance and discuss the potential mechanisms how IVIg might enhance Treg cells function. We propose that correction of Th17/Treg cell dysregulation could be one of the mechanisms that can explain the positive therapeutic effects of IVIg therapy. Consequently, selecting patients with abnormal Th17/Treg cell ratios could increase the success of IVIg therapy.