bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transcriptional basis of quantitative behavioral variation
Authors: Benowitz Kyle M. , McKinney Elizabeth C. , Cunningham Christopher B. , Moore Allen J. 
Published: February 2017

AbstractWhat causes individuals to produce quantitatively different phenotypes? While substantial research has focused on the allelic changes that affect phenotype, we know less about how gene expression accompanies variable phenotypes. Here, we investigate the transcriptional basis of variation in parental provisioning using two species of burying beetle,Nicrophorus orbicollisandNicrophorus vespilloides. Specifically, we used RNA-seq to compare the transcriptomes of parents that provided high amounts of provisioning behavior versus low amounts in males and females of each species. We found that there were no overarching transcriptional patterns that distinguish high from low caring parents, and no informative transcripts that displayed particularly large expression differences in females or males. However, we did find more subtle gene expression changes between high and low provisioning parents that are consistent across sexes as well as between the two species. Furthermore, we show that transcripts previously implicated in transitioning into parental care inN. vespilloideshad high variance in the levels of transcription and were unusually likely to display differential expression between high and low provisioning parents. Thus, quantitative behavioral variation appears to reflect many transcriptional differences of small effect. We show that nuanced regulation of the same gene products that are required for the transition of one behavioral state to another are also those influencing variation within a behavioral state.Author SummaryBurying beetles in the genusNicrophorusbreed on vertebrate carcasses and provide advanced parental care to their offspring by regurgitating partially digested flesh. However, all adult beetles do not uniformly express this trait. Some provide a large amount of parenting to their offspring, and some only a little. Here, we investigate the genetic causes of why someNicrophorusbeetles feed their offspring more than others. We demonstrate that this difference is likely caused by many small changes in gene expression, rather than a few genes that have major effects. We also find that some of the same genes that help to turn on parental care behavior in burying beetles also seem to play a role in determining how much care a beetle gives. These results provide new angles on longstanding questions about the complexity of the mechanisms that underlie quantitative variation in populations.
Extremely rare variants reveal patterns of germline mutation rate heterogeneity in humans
Authors: Carlson Jedidiah , Locke Adam E , Flickinger Matthew , Zawistowski Matthew , Levy Shawn ,   The BRIDGES Consortium, Myers Richard M , Boehnke Michael , Kang Hyun Min , Scott Laura J , Li Jun Z , Zöllner Sebastian 
Published: February 2017

AbstractA detailed understanding of the genome-wide variability of single-nucleotide germline mutation rates is essential to studying human genome evolution. Here we use ∼36 million singleton variants from 3,560 whole-genome sequences to infer fine-scale patterns of mutation rate heterogeneity. Mutability is jointly affected by adjacent nucleotide context and diverse genomic features of the surrounding region, including histone modifications, replication timing, and recombination rate, sometimes suggesting specific mutagenic mechanisms. Remarkably, GC content, DNase hypersensitivity, CpG islands, and H3K36 trimethylation are associated with both increased and decreased mutation rates depending on nucleotide context. We validate these estimated effects in an independent dataset of ∼46,000de novomutations, and confirm our estimates are more accurate than previously published estimates based on ancestrally older variants without considering genomic features. Our results thus provide the most refined portrait to date of the factors contributing to genome-wide variability of the human germline mutation rate.
MITE-based drives to transcriptional control of genome host
Authors: Vaschetto Luis María 
Published: February 2017

AbstractIn a recent past, Transposable Elements (TEs) were referred as selfish genetic components only capable of copying themselves with the aim to increase the odds that will be inherited. Nonetheless, TEs have been initially proposed as positive control elements acting in synergy with the host. Nowadays, it is well known that TE movement into genome host comprise an important evolutionary mechanism capable to produce diverse chromosome rearrangements and thus increase the adaptive fitness. According to as insights into TE functioning are increasing day to day, the manipulation of transposition has raised an interesting possibility to setting the host functions, although the lack of appropriate genome engineering tools has unpaved it. Fortunately, the emergence of genome editing technologies based on programmable nucleases, and especially the arrival of a multipurpose RNA-guided Cas9 endonuclease system, has made it possible to reconsider this challenge. For such purpose, a particular type of transposons referred as Miniature Inverted-repeat Transposable Elements (MITEs) has shown a series of interesting characteristics for designing functional drivers. Here, recent insights into MITE elements and versatile RNA-guided CRISPR/Cas9 genome engineering system are given to outline an effective strategy that allows to deploy the TE potential for control of the host transcriptional activity.
Ongoing human chromosome end extension revealed by analysis of BioNano and nanopore data
Authors: Shao Haojing , Zhou Chenxi , Cao Minh Duc , Coin Lachlan J.M. 
Published: February 2017

ABSTRACTThe majority of human chromosome ends remain incompletely assembled due to their highly repetitive structure. In this study, we use BioNano data to anchor and extend chromosome ends from two European trios as well as two unrelated Asian genomes. BioNano assembled chromosome ends are structurally divergent from the reference genome, including both missing sequence (10%) and extensions(22%). These extensions are heritable and in some cases divergent between Asian and European samples. Six ninths of the extension sequence in NA12878 can be confirmed and filled by nanopore data. We identify two sequence families in these sequences which have undergone substantial duplication in multiple primate lineages. We show that these sequence families have arisen from progenitor interstitial sequence on the ancestral primate chromosome 7. Comparison of chromosome end sequences from 15 species revealed that chromosome end missing sequence matches the corresponding phylogenetic relationship and revealed a rate of chromosome extension per chromosome of 0.0020 bp per year in average.
Biomedical Text Mining for Research Rigor and Integrity: Tasks, Challenges, Directions
Authors: Kilicoglu Halil 
Published: February 2017

AbstractAn estimated quarter of a trillion US dollars is invested in the biomedical research enterprise annually. There is growing alarm that a significant portion of this investment is wasted, due to problems in reproducibility of research findings and in the rigor and integrity of research conduct and reporting. Recent years have seen a flurry of activities focusing on standardization and guideline development to enhance the reproducibility and rigor of biomedical research. Research activity is primarily communicated via textual artifacts, ranging from grant applications to journal publications. These artifacts can be both the source and the end result of practices leading to research waste. For example, an article may describe a poorly designed experiment, or the authors may reach conclusions not supported by the evidence presented. In this article, we pose the question of whether biomedical text mining techniques can assist the stakeholders in the biomedical research enterprise in doing their part towards enhancing research integrity and rigor. In particular, we identify four key areas in which text mining techniques can make a significant contribution: plagiarism/fraud detection, ensuring adherence to reporting guidelines, managing information overload, and accurate citation/enhanced bibliometrics. We review the existing methods and tools for specific tasks, if they exist, or discuss relevant research that can provide guidance for future work. With the exponential increase in biomedical research output and the ability of text mining approaches to perform automatic tasks at large scale, we propose that such approaches can add checks and balances that promote responsible research practices and can provide significant benefits for the biomedical research enterprise.Supplementary informationSupplementary material is available atBioRxiv.
Identification of the primary peptide inhibitor contaminant of fibrillation and toxicity in synthetic Amyloid-β42
Authors: Adams Daniel J. , Nemkov Travis , Mayer John P. , Old William M. , Stowell Michael H. B. 
Published: February 2017

AbstractUnderstanding the pathophysiology of Alzheimer disease has relied upon the use of amyloid peptides from a variety of sources, but most predominantly synthetic peptides produced using t-butyloxycarbonyl (Boc) or 9-fluorenylmethoxycarbonyl (Fmoc) chemistry. These synthetic methods can lead to minor impurities which can have profound effects on the biological activity of amyloid peptides. Here we used a combination of cytotoxicity assays, fibrillation assays and high resolution mass spectrometry (MS) to identify impurities in synthetic amyloid preparations that inhibit both cytotoxicity and aggregation. We identify the Aβ42Δ39 species as the major peptide contaminant responsible for limiting both cytotoxicity and fibrillation of the amyloid peptide. In addition, we demonstrate that the presence of this minor impurity inhibits the formation of a stable Aβ42 dimer observable by MS in very pure peptide samples. These results highlight the critical importance of purity and provenance of amyloid peptides in Alzheimer’s research in particular, and biological research in general.
Can Ebola Virus evolve to be less virulent in humans?
Authors: Sofonea Mircea T. , Aldakak Lafi , Boullosa Luis Fernando , Alizon Samuel 
Published: February 2017

AbstractThis preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (<http://dx.doi.org/10.24072/pci.evolbiol.100022>). Understanding Ebola Virus (EBOV) virulence evolution is not only timely but also raises specific questions because it causes one of the most virulent human infections and it is capable of transmission after the death of its host. Using a compartmental epidemiological model that captures three transmission routes (by regular contact, via dead bodies and by sexual contact), we infer the evolutionary dynamics of case fatality ratio (CFR) on the scale of an outbreak and on the long term. Our major finding is that the virus’s specific life cycle imposes selection for high levels of virulence and that this pattern is robust to parameter variations in biological ranges. In addition to shedding a new light on the ultimate causes of EBOV’s high virulence, these results generate testable predictions and contribute to informing public health policies. In particular, burial management stands out as the most appropriate intervention since it decreases theR0of the epidemics, while imposing selection for less virulent strains.Impact SummaryThe severe haemorrhagic fever caused by Ebola Virus (EBOV) usually kills more than one infected individual out of two in the absence of treatment, which makes this pathogen one of the most virulent known to humans. The recent outbreak in West Africa (2013-2016) revealed that the virus is able to spread and persist for months across countries. It is often thought that virulence could be due to the fact that the virus is adapted to its reservoir host. Given that microbes evolve rapidly, it is important to determine whether EBOV virulence is likely to decrease as the virus adapts to its human host. To address this problem, we developed a novel mathematical model tailored to EBOV’s life cycle, notably by capturing its three main transmission routes (by regular contact, sexual contact and via dead bodies). We investigated the evolutionary trends of EBOV’s virulence on different time scales (outbreak initiation, short term and long term). Our results reveal that the virulence of EBOV might not be due to the maladaptation of the virus, but could rather originate from its unique life cycle. These results are robust to the parameter values chosen. From a public health perspective, burial management stands out as the main leverage to fight the virulence of EBOV, both on the short and long terms.
Unifying Temporal Phenomena in Human Visual Cortex
Authors: Zhou Jingyang , Benson Noah C. , Kay Kendrick , Winawer Jonathan 
Published: February 2017

AbstractNeuronal responses in visual cortex show a diversity of complex temporal properties. These properties include sub-additive temporal summation, response reduction with repeated or sustained stimuli (adaptation), and slower dynamics at low stimulus contrast. Here, we hypothesize that these seemingly disparate effects can be explained by a single, shared computational mechanism. We propose a model consisting of a linear stage, followed by history-dependent gain control. The model accounts for these various temporal phenomena, tested against an unusually diverse set of measurements - intracranial electrodes in patients, fMRI, and macaque single unit spiking. The model further enables us to uncover a systematic and rich variety of temporal encoding strategies across visual cortex: First, temporal receptive field shape differs both across and within visual field maps. Second, later visual areas show more rapid and pronounced adaptation. Our study provides a new framework to understand the transformation between visual input and dynamical cortical responses.Author SummaryThe nervous system extracts meaning from the distribution of light over space and time. Spatial vision has been a highly successful research area, and the spatial receptive field has served as a fundamental and unifying concept that spans perception, computation, and physiology. While there has also been a large interest in temporal vision, the temporal domain has lagged the spatial domain in terms of quantitative models of how signals are transformed across the visual hierarchy. Here we present a model of temporal dynamics of neuronal responses in human cerebral cortex. We show that the model can accurately predict responses at the millisecond scale using intracortical electrodes in patient volunteers, and that the same model generalizes to multiple types of other measurements, including functional MRI and action potentials from monkey cortex. Further, we show that a single model can account for a variety of temporal phenomena, including short-term adaptation and slower dynamics at low stimulus contrast. By developing a computational model and showing that it successfully generalizes across measurement types, cortical areas, and stimuli, we provide new insights into how time-varying images are encoded and transformed into dynamic cortical responses.
Numerical investigation on the heat transfer of a droplet-laden flow in a microfluidic system
Authors: Wang Rui-jin 
Published: February 2017

Purpose
This paper aims to explore the effectiveness and mechanism of a droplet-laden flow in a microfluidic system.

Design/methodology/approach
Numerical approach based on the volume of fluid method is implemented for modelling the forced heat transport in a droplet-laden flow in a microchannel.

Findings
The heat transfer effectiveness of droplet-laden flow is found to be obviously superior to that of a single-phase flow because of the circulation stream between the droplets. In addition, the effectiveness will be further increased when an elongated droplet is being laden because the circulation streams within and between the droplets are more pronounced. The elongated droplet size affects the heat transfer characteristics signified by Nusselt number, and there exists an optimum value at a fixed parameter.

Originality/value
This paper attempts to clarify the influence on the heat transfer performance when droplet with various shape and size being laden. This work is done by none before. This research work applies a solid foundation for designing a cooling system in microelectromechanical system.
Natural convection in a wavy porous cavity with sinusoidal heating and internal heat generation
Authors: Cheong Huey Tyng , Sivasankaran S. , Bhuvaneswari M. 
Published: February 2017

Purpose
The purpose of this paper is to study natural convective flow and heat transfer in a sinusoidally heated wavy porous cavity in the presence of internal heat generation or absorption.

Design/methodology/approach
Sinusoidal heating is applied on the vertical left wall of the cavity, whereas the wavy right wall is cooled at a constant temperature. The top and bottom walls are taken to be adiabatic. The Darcy model is adopted for fluid flow through the porous medium in the cavity. The governing equations and boundary conditions are solved using the finite difference method over a range of amplitudes and number of undulations of the wavy wall, Darcy–Rayleigh numbers and internal heat generation/absorption parameters.

Findings
The results are presented in the form of streamlines, isotherms and Nusselt numbers for different values of right wall waviness, Darcy–Rayleigh number and internal heat generation parameter. The flow field and temperature distribution in the cavity are affected by the waviness of the right wall. The wavy nature of the cavity also enhances the heat transfer into the system. The heat transfer rate in the cavity decreases with an increase in the internal heat generation/absorption parameter.

Research limitations/implications
The present investigation is conducted for steady, two-dimensional natural convective flow in a wavy cavity filled with Darcy porous medium. The waviness of the right wall is described by the amplitude and number of undulations with a well-defined mathematical function. An extension of the present study with the effects of cavity inclination and aspect ratio will be the interest for future work.

Practical implications
The study might be useful for the design of solar collectors, room ventilation systems and electronic cooling systems.

Originality/value
This work examines the effects of sinusoidal heating on convective heat transfer in a wavy porous cavity in the presence of internal heat generation or absorption. The study might be useful for the design of solar collectors, room ventilation systems and electronic cooling systems.
Influences of aspect ratio and wall boundary condition on laminar Rayleigh–Bénard convection of Bingham fluids in rectangular enclosures
Authors: Yigit Sahin , Chakraborty Nilanjan 
Published: February 2017

Purpose
This paper aims to investigate the aspect ratio (AR; ratio of enclosure height:length) dependence of steady-state Rayleigh–Bénard convection of Bingham fluids within rectangular enclosures for both constant wall temperature and constant wall heat flux boundary conditions. A nominal Rayleigh number range 103 ≤ Ra ≤ 105 (Ra defined based on the height) for a single representative value of nominal Prandtl number (i.e. Pr = 500) has been considered for 1/4 ≤ AR ≤ 4.

Design/methodology/approach
The bi-viscosity Bingham model is used to mimic Bingham fluids for Rayleigh–Bénard convection of Bingham fluids in rectangular enclosures. The conservation equations of mass, momentum and energy have been solved in a coupled manner using the finite volume method where a second-order central differencing scheme is used for the diffusive terms and a second-order up-wind scheme is used for the convective terms. The well-known semi-implicit method for pressure-linked equations algorithm is used for the coupling of the pressure and velocity.

Findings
It has been found that buoyancy-driven flow strengthens with increasing nominal Rayleigh number Ra, but the convective transport weakens with increasing Bingham number Bn, because of additional flow resistance arising from yield stress in Bingham fluids. The relative contribution of thermal conduction (advection) to the total thermal transport strengthens (diminishes) with increasing AR for a given set of values of Ra and Pr for both Newtonian and Bingham fluids for both boundary conditions, and the thermal transport takes place purely because of conduction for tall enclosures.

Originality/value
Correlations for the mean Nusselt number Nu
¯

have been proposed for both boundary conditions for both Newtonian and Bingham fluids using scaling arguments, and the correlations have been demonstrated to predict Nu
¯

obtained from simulation data for 1/4 ≤ AR ≤ 4, 103 ≤ Ra ≤ 105 and Pr = 500.
Effects of uniform magnetic field on the natural convection of Cu–water nanofluid in a triangular cavity
Authors: Javed T. , Mehmood Z. , Siddiqui M.A. , Pop Ioan 
Published: February 2017

Purpose
The purpose of this paper is to perform a numerical study for heat transfer through natural convection in the presence of a constant magnetic field in an incompressible steady nanofluid flow inside an isosceles triangular cavity.

Design/methodology/approach
For this flow problem, the left wall of the cavity subjected to uniform/nonuniform heat was considered, while right and bottom walls of the cavity were kept cold. The obtained equations were solved by using the Galerkin weighted residual technique. Results are computed for a wide range of parameters including Rayleigh number (Ra) (10^3 < Ra < 10^7), Hartman number (Ha) (0 < Ha < 60), and heat-generation/-absorption coefficient (q) (−10 < q < 10), while, Prandtl number (Pr) was kept fixed at 6.2. These computed results are presented in terms of stream functions, isotherms, Nusselt numbers and average Nusselt numbers through figures.

Findings
It is observed that, in case of uniform heating of the side wall, the strength of stream lines’ circulations increases with an increase in Ra and decreases with an increase in Ha. Similarly, by increasing heat-absorption coefficient q, an increase in the circulation strength is noted and the circulation cell moves towards the left wall in the presence of a heat sink (q < 0) and moves to the cold right wall in the presence of a heat source (q > 0). In the case of nonuniformly heated left wall in the presence of a heat source (q > 0), a higher-temperature gradient is observed in the cavity and isotherms are clustered to the left wall in the lower portion and to right wall in the upper portion; these appear to be straight and parallel to the x-axis near the bottom wall. On the other hand, the heat transfer rate along all the walls of the cavity is observed to be higher for smaller values of q. Whereas, Nusselt number along the bottom wall (Nu-B) increases with an increase in the values of x, while, that along the left wall (Nu-L) first increases and then decreases. But Nusselt number along the right wall (Nu-R) is found to be qualitatively opposite to Nu-L with an increase in distance x. Whereas, average Nusselt number increases with an increase in Rayleigh number Ra and heat-generation/-absorption coefficient q.

Research limitations/implications
The problem is formulated for an incompressible flow; viscous dissipation has been neglected, negligible induced magnetic field has been considered and local thermal equilibrium has been considered.

Originality/value
Results presented in this paper are original and new for the effects of a uniform magnetic field on the natural convection of Cu–water nanofluid in a triangular cavity. Hence, this study is important for researchers working in the area of heat transfer in cavity flows involving the nanofluid to become familiar with the flow behavior and properties.