bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topographic Signatures of Global Object Perception in Human Visual Cortex
Authors: Stoll Susanne , Finlayson Nonie J. , Schwarzkopf D. Samuel 
Published: December 2019

AbstractOur visual system readily groups dynamic fragmented input into global objects. How the brain represents such perceptual grouping remains however unclear. To address this question, we recorded brain responses using functional magnetic resonance imaging whilst observers perceived a dynamic bistable stimulus that could either be perceived globally (i.e., as a grouped and coherently moving shape) or locally (i.e., as ungrouped and incoherently moving elements). We further estimated population receptive fields and used these to back-project the brain activity during stimulus perception into visual space via a searchlight procedure. Global perception resulted in non-topographic suppression of responses in lower visual cortex accompanied by wide-spread enhancement in higher object-sensitive cortex. However, follow-up experiments indicated that higher object-sensitive cortex is suppressed if global perception lacks shape grouping, and that grouping-related suppression can be diffusely confined to stimulated sites once stimulus size is reduced. These results speak against a rigid between-area response amplitude code acting as a generic grouping mechanism and point to a within-area response amplitude code mediating the perception of figure and ground.
Increased yields of duplex sequencing data by a series of quality control tools
Authors: Povysil Gundula , Heinzl Monika , Salazar Renato , Stoler Nicholas , Nekrutenko Anton , Tiemann-Boege Irene 
Published: December 2019

AbstractDuplex sequencing is currently the most reliable method to identify ultra-low frequency DNA variants by grouping sequence reads derived from the same DNA molecule into families with information on the forward and reverse strand. However, only a small proportion of reads are assembled into duplex consensus sequences, and reads with potentially valuable information are discarded at different steps of the bioinformatics pipeline, especially reads without a family. We developed a bioinformatics tool-set that analyses the tag and family composition with the purpose to understand data loss and implement modifications to maximize the data output for the variant calling. Specifically, our tools show that tags contain PCR and sequencing errors that contribute to data loss and lower DCS yields. Our tools also identified chimeras, which result in unpaired families that do not form DCS. Finally, we also developed a tool called Variant Analyzer that re-examines variant calls from raw reads and provides different summary data that categorizes the confidence level of a variant call by a tier-based system. We demonstrate that this tool identified false positive variants tagged by the tier-based classification. Furthermore, with this tool we can include reads without a family and check the reliability of the call, which increases substantially the sequencing depth for variant calling, a particular important advantage for low-input samples or low-coverage regions.
Demographic history and genomics of local adaptation in blue tit populations
Authors: Charles Perrier , Quentin Rougemont , Anne Charmantier 
Published: December 2019

AbstractUnderstanding the genomic processes underlying local adaptation is a central aim of modern evolutionary biology. This task requires identifying footprints of local selection but also estimating spatio-temporal variation in population demography and variation in recombination rate and diversity along the genome. Here, we investigated these parameters in blue tit populations inhabiting deciduous versus evergreen forests and insular versus mainland areas, in the context of a previously described strong phenotypic differentiation. Neighboring population pairs of deciduous and evergreen habitats were weakly genetically differentiated (FST = 0.004 on average), nevertheless with a statistically significant effect of habitat type on the overall genetic structure. This low differentiation was consistent with the strong and long-lasting gene flow between populations, inferred by demographic modeling. In turn, insular and mainland populations were moderately differentiated (FST = 0.08 on average), in line with the inference of moderate ancestral migrations, followed by isolation since the end of the last glaciation. Effective population sizes were overall large, yet smaller on the island than on the mainland. Weak and non-parallel footprints of divergent selection between deciduous and evergreen populations were consistent with their high connectivity and the probable polygenic nature of local adaptation in these habitats. In turn, stronger footprints of divergent selection were identified between long isolated insular versus mainland birds, and were more often found in regions of low recombination as expected from theory. Lastly, we identified a genomic inversion on the mainland, spanning 2.8Mb. These results provide insights into the demographic history and genetic architecture of local adaptation in blue tit populations at multiple geographic scales.
Why the tumor cell metabolism is not that abnormal
Authors: Jacquet Pierre , Stéphanou Angélique 
Published: December 2019

AbstractThe cell energy metabolism is a multifactorial and evolving process that we address with a theoretical approach in order to decipher the functioning of the core system of the glycolysis-OXPHOS relationship. The model is based on some key experimental observations and well established facts. It emphasizes the role of lactate as a substrate, as well as the central role of pyruvate in the regulation of the metabolism. The simulations show how imposed environmental constraints and imposed energy requirements push the cell to adapt its metabolism to sustain its needs. The results highlight the cooperativeness of the two metabolic modes and allows to revisit the notions ofmetabolic switchandmetabolic reprogramming. Our results thus tend to show that the Warburg effect is not an inherent characteristic of the tumor cell, but a spontaneous and transitory adaptation mechanism to a disturbed environment. This means that the tumor cell metabolism is not fundamentally different from that of a normal cell. This has implications on the way therapies are being considered. The quest to normalize the tumor acidity could be a good strategy.Author SummaryCancer cells metabolism focuses the interest of the cancer research community. Although this process is intensely studied experimentally, there exists very few theoretical models that tackle this issue. One main reason is the extraordinary complexity of the metabolism that involves many inter-related regulation networks which makes it illusory to recreate computationally this complexity. In this study we propose a simplified model of the metabolism which focuses on the interrelation of the three main energetic metabolites that are oxygen, glucose and lactate with the aim to better understand the dynamic of the core system of the glycolysis-OXPHOS relationship. However simple, the model highlights the main rules that allow the cell to dynamically adapt its metabolism to its changing environment. It moreover allows to address this impact at the tissue scale. Simulations performed in a spheroid exhibit non-trivial spatial heterogeneity of the energy metabolism. It further reveals that the metabolic features that are commonly assigned to cancer cells are not necessarily due to cell intrinsic abnormality. They can emerge spontaneously because of the disregulated over-acidic environment.
Prolonged inflammation leads to ongoing damage after spinal cord injury
Authors: Kwiecien Jacek M. , Dabrowski Wojciech , Dąbrowska-Bouta Beata , Sulkowski Grzegorz , Oakden Wendy , Kwiecien-Delaney Christian J. , Yaron Jordan R. , Zhang Liqiang , Schutz Lauren , Marzec-Kotarska Barbara , Stanisz Greg J. , Karis John P. , Struzynska Lidia , Lucas Alexandra R. 
Published: December 2019

ABSTRACTThe pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains limited. Emerging evidence indicates the severity of post-SCI inflammation and an ongoing controversy in the roles of astrocytes with studies identifying astrocytes as associated both with ongoing inflammation and damage as well as potentially having a protective role. We have completed an extensive systematic study with MRI, histopathology, proteomics and ELISA analyses designed to further define the severe protracted and damaging inflammation after SCI in a rat model. We have identified 3 distinct phases of SCI: acute (first 2 days), inflammatory (starting day 3) and resolution (>3 months) in 16 weeks follow up. Actively phagocytizing, CD68+/CD163- macrophages infiltrate myelin-rich necrotic areas converting them into cavities of injury (COI) when deep in the spinal cord. Alternatively, superficial SCI areas are infiltrated by granulomatous tissue, or arachnoiditis where glial cells are obliterated. In the COI, CD68+/CD163- macrophage numbers reach a maximum in the first 4 weeks and then decline. Myelin phagocytosis is present at 16 weeks indicating ongoing inflammatory damage. The COI and arachnoiditis are defined by a wall of progressively hypertrophied astrocytes. MR imaging indicates persistent spinal cord edema that is linked to the severity of inflammation. Microhemorrhages in the spinal cord around the lesion are eliminated, presumably by reactive astrocytes within the first week post-injury. Acutely increased levels of TNF-α, IL-1β, IFN-γ and other pro-inflammatory cytokines, chemokines and proteases decrease and anti-inflammatory cytokines increase in later phases. In this study we elucidated a number of fundamental mechanisms in pathogenesis of SCI and have demonstrated a close association between progressive astrogliosis and reduction in the severity of inflammation.
MicroRNA miR-100 decreases glioblastoma growth by targeting SMARCA5 and ErbB3 in tumor-initiating cells
Authors: Alrfaei Bahauddeen M. , Vemuganti Raghu , Kuo John S. 
Published: December 2019

AbstractGlioblastoma multiforme (GBM) is the most aggressive and most frequently diagnosed malignant human glioma. Despite the best available standard of care (surgery, radiation, and chemotherapy), the median survival of GBM patients is less than 2 years. Many recent studies have indicated that microRNAs (miRNAs) are important for promoting or reducing/limiting GBM growth. In particular, we previously showed that GBMs express decreased levels of miR-100 relative to control tissue and that restoring miR-100 expression reduced GBM tumorigenicity by modulating SMRT/NCOR2 (Nuclear Receptor Corepressor 2). Here, we demonstrate that miR-100 overexpression decreases expression of the stem cell markers, nestin and L1CAM, and decreases proliferation of GBM tumor-initiating cells (GBM stem-like cells). We further show that miR-100-mediated anti-tumorigenic activity limits the activity of SMARCA5 and its downstream target STAT3 (known as mTOR-STAT3-Notch pathway). In addition, we report ErbB3 (Her3) as a putative miR-100 target, including inhibition of its downstream AKT and ERK signaling pathways.
Room without a view – den construction in relation to body size in brown bears
Authors: Shiratsuru Shotaro , Friebe Andrea , Swenson Jon E. , Zedrosser Andreas 
Published: December 2019

AbstractHibernation is an adaptive strategy to survive harsh winter conditions and food shortage. The use of well-insulated winter dens helps animals minimize energy loss during hibernation. Brown bears (Ursus arctos) commonly use excavated dens for hibernation. Physical properties of excavated dens, such as the amount of space between a bear and the inner wall, wall/roof thickness, and bedding materials, are expected to impact heat retention and energy conservation of bears. The objective of this study was to examine the impact of physical properties of excavated dens on energy conservation in hibernating bears. Our hypothesis was that bears excavate dens in a way to minimize heat loss and optimize energy conservation during hibernation. We predicted that physical properties of excavated dens would significantly affect the bears’ post-hibernation body condition. To test our hypothesis and prediction, we analyzed data collected from brown bears in Sweden with linear mixed effects models, examining (i) what factors affect den-excavation behavior and (ii) if physical properties of excavated dens affect post-hibernation body condition. We found that bears excavated a den cavity in relation to their body size, that older bears tended to excavate better-fitting den cavities compared to young bears, and that the physical properties of excavated dens did not significantly affect a bears’ post-hibernation body condition. Older bears excavated better-fitting den cavities, suggesting a potentially experience-based shift with age in den-excavation behavior and an optimum cavity size relative to a bear’s body size. The strong year effect shown by the most parsimonious model for post-hibernation body condition suggests that variations in physical properties of excavated dens are possibly negligible, compared to the large annual variations in biotic and abiotic factors affecting pre-hibernation body condition and heat loss during hibernation.
Epiviz File Server: Query, Transform and Interactively Explore Data from Indexed Genomic Files
Authors: Kancherla Jayaram , Yang Yifan , Chae Hyeyun , Bravo Hector Corrada 
Published: December 2019

AbstractGenomic data repositories like The Cancer Genome Atlas (TCGA), Encyclopedia of DNA Elements (ENCODE), Bioconductor’s AnnotationHub and ExperimentHub etc., provide public access to large amounts of genomic data as flat files. Researchers often download a subset of files data from these repositories to perform their data analysis. As these data repositories become larger, researchers often face bottlenecks in their exploratory data analysis. Based on the concepts of a NoDB paradigm, we developed epivizFileServer, a Python library that implements an in-situ data query system for local or remotely hosted indexed genomic files, not only for visualization but also data manipulation. The File Server library decouples data from analysis workflows and provides an abstract interface to define computations independent of the location, format or structure of the file.
Bipartite Tight Spectral Clustering (BiTSC) Algorithm for Identifying Conserved Gene Co-clusters in Two Species
Authors: Sun Yidan Eden , Zhou Heather J. , Li Jingyi Jessica 
Published: December 2019

AbstractGene clustering is a widely-used technique that has enabled computational prediction of unknown gene functions within a species. However, it remains a challenge to refine gene function prediction by leveraging evolutionarily conserved genes in another species. This challenge calls for a new computational algorithm to identify gene co-clusters in two species, so that genes in each co-cluster exhibit similar expression levels in each species and strong conservation between the species. Here we develop the bipartite tight spectral clustering (BiTSC) algorithm, which identifies gene co-clusters in two species based on gene orthology information and gene expression data. BiTSC novelly implements a formulation that encodes gene orthology as a bipartite network and gene expression data as node covariates. This formulation allows BiTSC to adopt and combine the advantages of multiple unsupervised learning techniques: kernel enhancement, bipartite spectral clustering, consensus clustering, tight clustering, and hierarchical clustering. As a result, BiTSC is a flexible and robust algorithm capable of identifying informative gene co-clusters without forcing all genes into co-clusters. Another advantage of BiTSC is that it does not rely on any distributional assumptions. Beyond cross-species gene co-clustering, BiTSC also has wide applications as a general algorithm for identifying tight node co-clusters in any bipartite network with node covariates. We demonstrate the accuracy and robustness of BiTSC through comprehensive simulation studies. In a real data example, we use BiTSC to identify conserved gene co-clusters of D. melanogaster and C. elegans, and we perform a series of downstream analysis to both validate BiTSC and verify the biological significance of the identified co-clusters.
Massively parallel discovery of human-specific substitutions that alter neurodevelopmental enhancer activity
Authors: Uebbing Severin , Gockley Jake , Reilly Steven K. , Kocher Acadia A. , Geller Evan , Gandotra Neeru , Scharfe Curt , Cotney Justin , Noonan James P. 
Published: December 2019

AbstractGenetic changes that altered the function of gene regulatory elements have been implicated in the evolution of the human brain. However, identifying the particular changes that modified regulatory activity during neurodevelopment remains challenging. Here we used massively parallel enhancer assays in human neural stem cells to measure the impact of 32,776 human-specific substitutions on enhancer activity in 1,363 Human Accelerated Regions (HARs) and 3,027 Human Gain Enhancers (HGEs), which include enhancers with novel activities in humans. We found that 31.9% of active HARs and 36.4% of active HGEs exhibited differential activity between human and chimpanzee. This enabled us to isolate the effects of 401 human-specific substitutions from other types of genetic variation in HARs and HGEs. Substitutions acted in both an additive and non-additive manner to alter enhancer activity. Human-specific substitutions altered predicted binding sites for a specific set of human transcription factors (TFs) that were a subset of TF binding sites associated with enhancer activity in our assay. Substitutions within HARs, which are overall highly constrained compared to HGEs, showed smaller effects on enhancer activity, suggesting that the impact of human-specific substitutions may be buffered in enhancers with constrained ancestral functions. Our findings yield insight into the mechanisms by which human-specific genetic changes impact enhancer function and provide a rich set of candidates for experimental studies of regulatory evolution in humans.
Clair: Exploring the limit of using a deep neural network on pileup data for germline variant calling
Authors: Luo Ruibang , Wong Chak-Lim , Wong Yat-Sing , Tang Chi-Ian , Liu Chi-Man , Leung Chi-Ming , Lam Tak-Wah 
Published: December 2019

AbstractSingle-molecule sequencing technologies have emerged in recent years and revolutionized structural variant calling, complex genome assembly, and epigenetic mark detection. However, the lack of a highly accurate small variant caller has limited the new technologies from being more widely used. In this study, we present Clair, the successor to Clairvoyante, a program for fast and accurate germline small variant calling, using single molecule sequencing data. For ONT data, Clair achieves the best precision, recall and speed as compared to several competing programs, including Clairvoyante, Longshot and Medaka. Through studying the missed variants and benchmarking intentionally overfitted models, we found that Clair may be approaching the limit of possible accuracy for germline small variant calling using pileup data and deep neural networks. Clair requires only a conventional CPU for variant calling and is an open source project available at https://github.com/HKU-BAL/Clair.
Striving for sustainable graduate careers
Authors: Donald William E. , Baruch Yehuda , Ashleigh Melanie J. 
Published: December 2019

Purpose
The purpose of this paper is to conceptually articulate the differing needs of graduates and graduate employers, which can be competing or complementary in nature. Drawing from theoretical frameworks of career ecosystems and the new psychological contract, a set of propositions are presented using three themes: career management, development of talent and technological change.

Design/methodology/approach
A conceptual design offering a conceptual model through adopting the career ecosystem and new psychological contract as a framework.

Findings
These propositions offer a new conceptual model, which provides a practical contribution by articulating sustainability of graduates’ careers through employability at the graduate level and competitive advantage at the employer level.

Originality/value
The paper offers important contributions to theory by connecting career management and vocational career literature through acknowledging shared constructs of life-long learning and sustainable employability for graduates. These two streams are often developed in parallel, thus this paper helps to bridge the gaps in respective research agendas. This paper therefore has the originality of helping to advance the fields of career theory and sustainable human resource management.
Effect of finite wall thickness on entropy generation and natural convection in a nanofluid-filled partially heated square cavity
Authors: Ishak Muhamad Safwan , Alsabery Ammar I. , Chamkha A. , Hashim Ishak 
Published: December 2019

Purpose
The purpose of this paper is to study the effects of finite wall thickness on the natural convection and entropy generation in a square cavity filled with Al2O3–water nanofluid in the presence of bottom heat source.

Design/methodology/approach
The moving isothermal heater was placed on the bottom solid wall. The vertical walls (left and right walls) were fully maintained at low temperatures. The rest of the bottom solid wall along with the top horizontal wall was kept adiabatic. The boundaries of the domain are assumed to be impermeable; the fluid within the cavity is a water-based nanofluid having Al2O3 nanoparticles. The Boussinesq approximation is applicable. The dimensionless governing equations subject to the selected boundary conditions are solved using the finite difference method. The current proposed numerical method is proven excellent through comparisons with the existing experimental and numerical published studies.

Findings
Numerical results were demonstrated graphically in several forms including streamlines, isotherms and local entropy generation, as well as the local and average Nusselt numbers. The results reveal that the thermal conductivity and thickness of the solid wall are important control parameters for optimization of heat transfer and Bejan number within the partially heated square cavity.

Originality/value
According to the past research studies mentioned above and to the best of the authors’ knowledge, the gap regarding the problem with entropy generation analysis and natural convection in partially heated square cavity has yet to be filled. Because of this, this study aims to investigate the entropy generation analysis as well as the natural convection in nanofluid-filled square cavity which was heated partially. A square cavity with an isothermal heater located on the bottom solid horizontal wall of the cavity and partly cold sidewalls are essential problems in thermal processing applications. Hence, the authors believe that this present work will be a valuable contribution in improving the thermal performance.