bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-zone tumor tolerance can arise from a simple immunological feedforward motif that estimates tumor growth rates
Authors: Sontag Eduardo D. 
Published: December 2016

AbstractSince the early 1990s, many authors have independently suggested that self/nonself recognition by the immune system might be modulated by the rates of change of antigen challenges. This paper introduces an extremely simple and purely conceptual mathematical model that allows dynamic discrimination of immune challenges. The main component of the model is a motif which is ubiquitous in systems biology, the incoherent feedforward loop, which endows the system with the capability to estimate exponential growth exponents, a prediction which is consistent with experimental work showing that exponentially increasing antigen stimulation is a determinant of immune reactivity. Combined with a bistable system and a simple feedback repression mechanism, an interesting phenomenon emerges as a tumor growth rate increases: elimination, tolerance (tumor growth), again elimination, and finally a second zone of tolerance (tumor escape). This prediction from our model is analogous to the “two-zone tumor tolerance” phenomenon experimentally validated since the mid 1970s. Moreover, we provide a plausible biological instantiation of our circuit using combinations of regulatory and effector T cells.
Umap and Bismap: quantifying genome and methylome mappability
Authors: Karimzadeh Mehran , Ernst Carl , Kundaje Anshul , Hoffman Michael M. 
Published: December 2016

AbstractMotivationShort-read sequencing enables assessment of genetic and biochemical traits of individual genomic regions, such as the location of genetic variation, protein binding, and chemical modifications. Every region in a genome assembly has a property calledmappabilitywhich measures the extent to which it can be uniquely mapped by sequence reads. In regions of lower mappability, estimates of genomic and epigenomic characteristics from sequencing assays are less reliable. At best, sequencing assays will produce misleadingly low numbers of reads in these regions. At worst, these regions have increased susceptibility to spurious mapping from reads from other regions of the genome with sequencing errors or unexpected genetic variation. Bisulfite sequencing approaches used to identify DNA methylation exacerbate these problems by introducing large numbers of reads that map to multiple regions. While many tools consider mappability during the read mapping process, subsequent analysis often loses this information. Both to correct assumptions of uniformity in downstream analysis, and to identify regions where the analysis is less reliable, it is necessary to know the mappability of both ordinary and bisulfite-converted genomes.ResultsWe introduce the Umap software for identifying uniquely mappable regions of any genome. Its Bismap extension identifies mappability of the bisulfite-converted genome. With a read length of 24 bp, 18.7% of the unmodified genome and 33.5% of the bisulfite-converted genome is not uniquely mappable. This complicates interpretation of functional genomics experiments using short-read sequencing, especially in regulatory regions. For example, 81% of human CpG islands overlap with regions that are not uniquely mappable. Similarly, in some ENCODE ChIP-seq datasets, up to 50% of peaks overlap with regions that are not uniquely mappable. We also explored differentially methylated regions from a case-control study and identified regions that were not uniquely mappable. In the widely used 450K methylation array, 4,230 probes are not uniquely mappable. Genome mappability is higher with longer sequencing reads, but most publicly available ChIP-seq and reduced representation bisulfite sequencing datasets have shorter reads. Therefore, uneven and low mappability remains a concern in a majority of existing data.AvailabilityA Umap and Bismap track hub for human genome assemblies GRCh37/hg19 and GRCh38/hg38, and mouse assemblies GRCm37/mm9 and GRCm38/mm10 is available athttp://bismap.hoffmanlab.orgfor use with the UCSC and Ensembl genome browsers. We have deposited in Zenodo the current version of our software (https://doi.org/10.5281/zenodo.800648) and the mappability data used in this project (https://doi.org/10.5281/zenodo.800645). In addition, the software (https://bitbucket.org/hoffmanlab/umap) is freely available under the GNU General Public License, version 3 (GPLv3).Contactmichael.hoffman@utoronto.ca
Whole genome sequence accuracy is improved by replication in a population of mutagenized sorghum
Authors: Addo-Quaye Charles , Tuinstra Mitch , Carraro Nicola , Weil Clifford , Dilkes Brian P. 
Published: December 2016

ABSTRACTThe accurate detection of induced mutations is critical for both forward and reverse genetics studies. Experimental chemical mutagenesis induces relatively few single base changes per individual. In a complex eukaryotic genome, false positive detection of mutations can occur at or above this mutagenesis rate. We demonstrate here, using a population of ethyl methanesulfonate (EMS) treatedSorghum bicolorBTx623 individuals, that using replication to detect false positive induced variants in next-generation sequencing data permits higher throughput variant detection with greater accuracy. We used a lower sequence coverage depth (average of 7X) from 586 independently mutagenized individuals and detected 5,399,493 homozygous SNPs. Of these, 76% originated from only 57,872 genomic positions prone to false positive variant calling. These positions are characterized by high copy number paralogs where the error-prone SNP positions are at copies containing a variant at the SNP position. The ability of short stretches of homology to generate these error prone positions suggests that incompletely assembled or poorly mapped repeated sequences are one driver of these error prone positions. Removal of these false positives left 1,275,872 homozygous and 477,531 heterozygous EMS-induced SNPs which, congruent with the mutagenic mechanism of EMS, were greater than 98% G:C to A:T transitions. Through this analysis we generated a database of sequence indexed mutants of Sorghum. This collection contains 4,035 high impact homozygous mutations in 3,637 genes and 56,514 homozygous missense mutations in 23,227 genes. Each line contains, on average, 2,177 annotated homozygous SNPs per genome, including seven likely gene knockouts and 96 missense mutations. The number of mutations in a transcript was linearly correlated with the transcript length and also the G+C count, but not with the GC/AT ratio. Analysis of the detected mutagenized positions identified CG-rich patches, and flanking sequences strongly influenced EMS-induced mutation rates. Our method for detecting false-positive induced mutations is generally applicable to any organism, is independent of the choice ofin silicovariant-calling algorithm, and is most valuable when the true mutation rate is likely to be low, such as in laboratory induced mutations or somatic mutation detection in medicine.
Gene fractionation and function in the ancient subgenomes of maize
Authors: Renny-Byfield Simon , Rodgers-Melnick Eli , Ross-Ibarra Jeffrey 
Published: December 2016

AbstractThe maize genome experienced an ancient whole genome duplication approximately 10 million years ago and the duplicate subgenomes have since experienced reciprocal gene loss (fractionation) such that many genes have returned to single-copy status. This process has not affected the subgenomes equally; reduced gene expression in one of the subgenomes mitigates the consequences of mutations and gene deletions and is thought to drive higher rates of fractionation. Here we take advantage of published genome-wide SNP and phenotype association data to show that, in accordance with predictions of this model, paralogs with greater expression contribute more to phenotypic variation compared to their lowly expressed counterparts. Furthermore, paralogous genes in the least-fractionated subgenome account for a greater degree of phenotypic diversity than those resident on the more-fractionated subgenome. We also show that the two subgenomes of maize are distinct in epigenetic characteristics. Intriguingly, analysis of singleton genes reveals that these differences persist even after fractionation is complete.
Myotome adaptability confers developmental robustness to somitic myogenesis in response to fibre number alteration
Authors: Roy Shukolpa D. , Williams Victoria C. , Pipalia Tapan G. , Li Kuoyu , Hammond Christina L. , Knappe Stefanie , Knight Robert D. , Hughes Simon M. 
Published: December 2016

Summary StatementHomeostatic interactions between muscle stem cells and fibres during myogenesis ensure the correct muscle size is formed independent of fibre number in zebrafishAbstractBalancing the number of stem cells and their progeny is crucial for tissue development and repair. Here we examine how muscle stem/precursor cell (MPC) numbers are tightly regulated during zebrafish somitic muscle development. MPCs expressing Pax7 are initially located in the dermomyotome (DM) external cell layer, adopt a highly stereotypical distribution and thereafter a proportion of MPCs migrate into the myotome. Regional variations in the proliferation and terminal differentiation of MPCs contribute to growth of the myotome. To probe the robustness of spatiotemporal regulation of MPCs, we compared the behaviour of wild type (wt) MPCs with those in mutant zebrafish that lack the muscle regulatory factor Myod.Myodfh261mutants form one third fewer multinucleate fast muscle fibres than wt and show a significant expansion of the Pax7+MPC population in the DM. Subsequently,myodfh261mutant fibres generate more cytoplasm per nucleus, leading to recovery of muscle bulk. In addition, relative to wt siblings, there is an increased number of MPCs inmyodfh261mutants and these migrate prematurely into the myotome, differentiate and contribute to the hypertrophy of existing fibres. Thus, homeostatic reduction of the excess MPCs returns their number to normal levels, but fibre numbers remain low. The GSK3 antagonist BIO prevents MPC migration into the deep myotome, suggesting that canonical Wnt pathway activation maintains the DM in zebrafish, as in amniotes. BIO does not, however, block recovery of themyodfh261mutant myotome, indicating that homeostasis acts on fibre intrinsic growth to maintain muscle bulk. The findings suggest the existence of a critical window for early fast fibre formation followed by a period in which homeostatic mechanisms regulate myotome growth by controlling fibre size.
When null hypothesis significance testing is unsuitable for research: a reassessment
Authors: Szucs Denes , Ioannidis John PA 
Published: December 2016

AbstractNull hypothesis significance testing (NHST) has several shortcomings that are likely contributing factors behind the widely debated replication crisis of psychology, cognitive neuroscience and biomedical science in general. We review these shortcomings and suggest that, after about 60 years of negative experience, NHST should no longer be the default, dominant statistical practice of all biomedical and psychological research. Different inferential methods (NHST, likelihood estimation, Bayesian methods, false-discovery rate control) may be most suitable for different types of research questions. Whenever researchers use NHST they should justify its use, and publish pre-study power calculations and effect sizes, including negative findings. Studies should optimally be pre-registered and raw data published. The current statistics lite educational approach for students that has sustained the widespread, spurious use of NHST should be phased out. Instead, we should encourage either more in-depth statistical training of more researchers and/or more widespread involvement of professional statisticians in all research.
Mitochondrial-nuclear interactions maintain geographic separation of deeply diverged mitochondrial lineages in the face of nuclear gene flow
Authors: Morales Hernán E. , Pavlova Alexandra , Amos Nevil , Major Richard , Kilian Andrzej , Greening Chris , Sunnucks Paul 
Published: December 2016

AbstractMetabolic processes in eukaryotic cells depend on interactions between mitochondrial and nuclear gene products (mitonuclear interactions). These interactions could play a direct role in population divergence. We studied the evolution of mitonuclear interactions in a widespread passerine that experienced population divergence followed by bi-directional mitochondrial introgression into different nuclear backgrounds. Using >60,000 SNPs, we quantified patterns of nuclear genetic differentiation between populations that occupy different climates and harbour deeply divergent mitolineages despite ongoing nuclear gene flow. Analyses were performed independently for two sampling transects intersecting mitochondrial divergence in different nuclear backgrounds. In both transects, low genome-wide nuclear differentiation was accompanied by strong differentiation at a ~15.4 Mb region of chromosome 1A. This region is enriched for genes performing mitochondrial functions. Molecular signatures of selective sweeps in this region alongside those in the mitochondrial genome suggest a history of adaptive mitonuclear co-introgression. The chromosome 1A region has elevated linkage disequilibrium, suggesting that selection on genomic architecture may favour low recombination among nuclear-encoded genes with mitochondrial functions. In this system, mitonuclear interactions appear to maintain the geographic separation of two mitolineages in the face of nuclear gene flow, supporting mitonuclear co-evolution as an important vehicle for climatic adaptation and population divergence.
Partitioned Learning of Deep Boltzmann Machines for SNP Data
Authors: Hess Moritz , Lenz Stefan , Blätte Tamara J , Bullinger Lars , Binder Harald 
Published: December 2016

AbstractLearning the joint distributions of measurements, and in particular identification of an appropriate low-dimensional manifold, has been found to be a powerful ingredient of deep leaning approaches. Yet, such approaches have hardly been applied to single nucleotide polymorphism (SNP) data, probably due to the high number of features typically exceeding the number of studied individuals. After a brief overview of how deep Boltzmann machines (DBMs), a deep learning approach, can be adapted to SNP data in principle, we specifically present a way to alleviate the dimensionality problem by partitioned learning. We propose a sparse regression approach to coarsely screen the joint distribution of SNPs, followed by training several DBMs on SNP partitions that were identified by the screening. Aggregate features representing SNP patterns and the corresponding SNPs are extracted from the DBMs by a combination of statistical tests and sparse regression. In simulated case-control data, we show how this can uncover complex SNP patterns and augment results from univariate approaches, while maintaining type 1 error control. Time-to-event endpoints are considered in an application with acute myeloid lymphoma patients, where SNP patterns are modeled after a pre-screening based on gene expression data. The proposed approach identified three SNPs that seem to jointly influence survival in a validation data set. This indicates the added value of jointly investigating SNPs compared to standard univariate analyses and makes partitioned learning of DBMs an interesting complementary approach when analyzing SNP data.
Adversarial Deep Structural Networks for Mammographic Mass Segmentation
Authors: Zhu Wentao , Xie Xiaohui 
Published: December 2016

AbstractMass segmentation is an important task in mammogram analysis, providing effective morphological features and regions of interest (ROI) for mass detection and classification. Inspired by the success of using deep convolutional features for natural image analysis and conditional random fields (CRF) for structural learning, we propose an end-to-end network for mammographic mass segmentation. The network employs a fully convolutional network (FCN) to model potential function, followed by a CRF to perform structural learning. Because the mass distribution varies greatly with pixel position, the FCN is combined with position priori for the task. Due to the small size of mammogram datasets, we use adversarial training to control over-fitting. Four models with different convolutional kernels are further fused to improve the segmentation results. Experimental results on two public datasets, INbreast and DDSM-BCRP, show that our end-to-end network combined with adversarial training achieves the-state-of-the-art results.
Surface science at the PEARL beamline of the Swiss Light Source
Authors: Muntwiler Matthias , Zhang Jun , Stania Roland , Matsui Fumihiko , Oberta Peter , Flechsig Uwe , Patthey Luc , Quitmann Christoph , Glatzel Thilo , Widmer Roland , Meyer Ernst , Jung Thomas A. , Aebi Philipp , Fasel Roman , Greber Thomas 
Published: December 2016

The Photo-Emission and Atomic Resolution Laboratory (PEARL) is a new soft X-ray beamline and surface science laboratory at the Swiss Light Source. PEARL is dedicated to the structural characterization of local bonding geometry at surfaces and interfaces of novel materials, in particular of molecular adsorbates, nanostructured surfaces, and surfaces of complex materials. The main experimental techniques are soft X-ray photoelectron spectroscopy, photoelectron diffraction, and scanning tunneling microscopy (STM). Photoelectron diffraction in angle-scanned mode measures bonding angles of atoms near the emitter atom, and thus allows the orientation of small molecules on a substrate to be determined. In energy scanned mode it measures the distance between the emitter and neighboring atoms; for example, between adsorbate and substrate. STM provides complementary, real-space information, and is particularly useful for comparing the sample quality with reference measurements. In this article, the key features and measured performance data of the beamline and the experimental station are presented. As scientific examples, the adsorbate–substrate distance in hexagonal boron nitride on Ni(111), surface quantum well states in a metal-organic network of dicyano-anthracene on Cu(111), and circular dichroism in the photoelectron diffraction of Cu(111) are discussed.
In-between strengthened accessibility and economic demands
Authors: Engström Lisa , Rivano Eckerdal Johanna 
Published: December 2016

Purpose
The purpose of this paper is to explore the implementation of self-service at public libraries from the perspective of their users. The implementation of self-service is related to a diverse societal context including, for example, an overall digitalisation, budget constraints and political expectations on public libraries to contribute to marketing the local community.

Design/methodology/approach
Semi-structured interviews with users and observations have been undertaken at self-service libraries in the south of Sweden. The material is analysed by means of a theoretical framework consisting of previous critical LIS-research, Fairclough’s critical discourse analysis and Habermas’ theory of the colonisation of the life world.

Findings
The implementation of self-service is affecting the users’ library practices as well as their expectations on the library. These expectations are shaped by various and sometimes competing discourses.

Social implications
To support public libraries’ role as democratic, public spheres, the complexity of the users’ understandings should be taken into consideration when implementing self-service.

Originality/value
The differing expectations articulated by the users, and the various discourses they can be related to, implicate a hegemonic struggle, corresponding to a changing view on public libraries.
An analytical approach to building a core ontology for food
Authors: Madalli Devika P. , Chatterjee Usashi , Dutta Biswanath 
Published: December 2016

PurposeThe purpose of this paper is to demonstrate the construction of a core ontology for food. To construct the core ontology, the authors propose here an approach called, yet another methodology for ontology plus (YAMO+). The goal is to exhibit the construction of a core ontology for a domain, which can be further extended and converted into application ontologies.Design/methodology/approachTo motivate the construction of the core ontology for food, the authors have first articulated a set of application scenarios. The idea is that the constructed core ontology can be used to build application-specific ontologies for those scenarios. As part of the developmental approach to core ontology, the authors have proposed a methodology called YAMO+. It is designed following the theory of analytico-synthetic classification. YAMO+ is generic in nature and can be applied to build core ontologies for any domain.FindingsConstruction of a core ontology needs a thorough understanding of the domain and domain requirements. There are various challenges involved in constructing a core ontology as discussed in this paper. The proposed approach has proven to be sturdy enough to face the challenges that the construction of a core ontology poses. It is observed that core ontology is amenable to conversion to an application ontology.Practical implicationsThe constructed core ontology for domain food can be readily used for developing application ontologies related to food. The proposed methodology YAMO+ can be applied to build core ontologies for any domain.Originality/valueAs per the knowledge, the proposed approach is the first attempt based on the study of the state of the art literature, in terms of, a formal approach to the design of a core ontology. Also, the constructed core ontology for food is the first one as there is no such ontology available on the web for domain food.
GAFA speaks: metaphors in the promotion of cloud technology
Authors: Lindh Maria , Nolin Jan Michael 
Published: December 2016

Purpose
The purpose of this paper is to explore persuasive rhetoric by critically scrutinizing metaphorical devices utilized by leaders of the cloud industry. This paper introduces a critical approach to the promotion of cloud technology.

Design/methodology/approach
In total, 13 video clips from YouTube were analyzed, containing presentations and talks delivered by leaders of Google, Apple, Facebook and Amazon – four of the most influential companies within the information technology industry, sometimes referred to as GAFA. With the help of conceptual metaphor theory, often-repeated metaphors for cloud technologies reveal what properties were promoted and hidden.

Findings
GAFA mainly used the same persuasive metaphors to promote cloud computing’s positive aspects. Potentially negative or complex issues were mostly avoided. Cloud technology was uniformly described in metaphors of control, empowerment, transformation and automation. Implicitly, GAFA exerts power through the extensive dissemination of their metaphors and these are used in order to negotiate and overcome doubts about cloud computing and related technologies.

Originality/value
This is the first study aimed at understanding the persuasive rhetoric of GAFA, seen as a uniform object of study.