bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentially singular solutions of the 3D axisymmetric Euler equations
Authors: Luo Guo , Hou Thomas Y. 
Published: August 2014

Significance
Whether infinitely fast spinning vortices can develop in initially smooth, incompressible inviscid flow fields in finite time is one of the most challenging problems in fluid dynamics. Besides being a difficult mathematical question that has remained open for more than 250 years, the problem also attracts great attention in the physics and engineering communities due to its potential connection to the onset of turbulence in viscous flows. This paper attempts to provide an affirmative answer to this long-standing open question from a numerical point of view, by describing a class of rotationally symmetric flows from which infinitely fast spinning vortices can form in finite time. It suggests, after decades of controversies, a promising direction to the resolution of the problem.
Nonlinear conduction via solitons in a topological mechanical insulator
Authors: Chen Bryan Gin-ge , Upadhyaya Nitin , Vitelli Vincenzo 
Published: August 2014

Significance
Mechanisms are zero-energy motions that are key to the operation of mechanical devices, from windshield wipers to robotic arms. We built and studied chain-like mechanisms of coupled rigid rotors that are topologically protected, which means that they are not affected by smooth changes in material parameters like their quantum analogues. These prototypes are examples of mechanical structures that we dub topological metamaterials. Their mechanical excitations are nonlinear solitary waves which are topologically protected and yet tunable by changing the geometry of the unit cell. Although the left and right edges of the sample are equivalent in terms of local constraint counting, the solitary waves can start propagating only from the edge singled out by the topological polarization of the chain.
The Two-pore channel (TPC) interactome unmasks isoform-specific roles for TPCs in endolysosomal morphology and cell pigmentation
Authors: Lin-Moshier Yaping , Keebler Michael V. , Hooper Robert , Boulware Michael J. , Liu Xiaolong , Churamani Dev , Abood Mary E. , Walseth Timothy F. , Brailoiu Eugen , Patel Sandip , Marchant Jonathan S. 
Published: August 2014

Significance
Two-pore channels (TPCs) are a recently discovered family of endolysosomal ion channels, but their regulation is controversial. By defining the TPC interactome, we provide a community resource that illuminates TPC complex regulation and resolves associations with novel partners and processes. Physical interactions with endolysosomal trafficking regulators predominate, and Rab GTPases impart isoform-specific roles for TPCs in organelle proliferation and cellular pigmentation. These data imply a fundamental role for TPCs in trafficking that augurs significance for disease states exhibiting lysosomal proliferation where TPC dysregulation may drive pathogenesis.
Comparative analysis of pseudogenes across three phyla
Authors: Sisu Cristina , Pei Baikang , Leng Jing , Frankish Adam , Zhang Yan , Balasubramanian Suganthi , Harte Rachel , Wang Daifeng , Rutenberg-Schoenberg Michael , Clark Wyatt , Diekhans Mark , Rozowsky Joel , Hubbard Tim , Harrow Jennifer , Gerstein Mark B. 
Published: August 2014

Significance
Pseudogenes have long been considered nonfunctional elements. However, recent studies have shown they can potentially regulate the expression of protein-coding genes. Capitalizing on available functional-genomics data and the finished annotation of human, worm, and fly, we compared the pseudogene complements across the three phyla. We found that in contrast to protein-coding genes, pseudogenes are highly lineage specific, reflecting genome history more so than the conservation of essential biological functions. Specifically, the human pseudogene complement reflects a massive burst of retrotranspositional activity at the dawn of the primates, whereas the worm’s and fly's repertoire reflects a history of deactivated duplications. However, we also observe that pseudogenes across the three phyla have a consistent level of partial activity, with ∼15% being transcribed.
Temporally defined neocortical translation and polysome assembly are determined by the RNA-binding protein Hu antigen R
Authors: Kraushar Matthew L. , Thompson Kevin , Wijeratne H. R. Sagara , Viljetic Barbara , Sakers Kristina , Marson Justin W. , Kontoyiannis Dimitris L. , Buyske Steven , Hart Ronald P. , Rasin Mladen-Roko 
Published: August 2014

Significance
The neocortex is an intricate and diverse cellular network in the brain, generating complex thought and voluntary motor behavior. Although recent attention has focused on the genome and transcriptome, our goal is to study the role of posttranscriptional processing and mRNA translation in neocortical development. In this work, we show that the protein components of actively translating ribosomes and their mRNA cargo in the developing neocortex depend on the temporally specific action of an RNA-binding protein, Hu antigen R (HuR). We further show that HuR is required for the development of neocortical neurons and structure. This study contributes to our overall understanding of how the regulation of functional gene expression influences neocortical development.
Diversity and clonal selection in the human T-cell repertoire
Authors: Qi Qian , Liu Yi , Cheng Yong , Glanville Jacob , Zhang David , Lee Ji-Yeun , Olshen Richard A. , Weyand Cornelia M. , Boyd Scott D. , Goronzy Jörg J. 
Published: August 2014

SignificanceA decline in the diversity of the T-cell receptor repertoire owing to thymic involution has been implicated as causing defective immune responses in the elderly. By applying next-generation sequencing of replicate TCRB libraries from highly purified T-cell subsets, and using nonparametric statistical analysis, we obtain estimates of repertoire richness in the young adult that are higher than previously reported. Although contracting with age, the repertoire remains highly diverse. These data challenge the paradigm that thymic rejuvenation is needed to maintain diversity and prevent immune incompetence in the elderly. However, we observe an increasing inequality of clonal sizes with age even among naïve T cells. This clonal selection could result in biased and possibly autoreactive immune responses.
Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatment
Authors: Lecoutey Cédric , Hedou Damien , Freret Thomas , Giannoni Patrizia , Gaven Florence , Since Marc , Bouet Valentine , Ballandonne Céline , Corvaisier Sophie , Malzert Fréon Aurélie , Mignani Serge , Cresteil Thierry , Boulouard Michel , Claeysen Sylvie , Rochais Christophe , Dallemagne Patrick 
Published: August 2014

Significance
Targeting more than one molecular cause implied in the pathogenesis of Alzheimer’s disease (AD) with a sole drug is considered a promising challenge, because it may address the numerous failures that recently occurred during clinical trials that were conducted in this area. Donecopride has been designed by us as a multitarget-directed ligand, targeting both serotonin subtype 4 receptor and acetylcholinesterase with excellent in vitro activities. The latter seems able to not only restore the cholinergic neurotransmission altered in AD but also, promote the secretion of a neurotrophic protein that is detrimental to the neurotoxic amyloid-β peptide. With its excellent drugability, donecopride further displayed significant procognitive effects in mice and generated a promising lead for a previously unidentified approach in AD treatment.
RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection
Authors: Wang Jianbin , Quake Stephen R. 
Published: August 2014

Significance
Latent viral infection is a major obstacle for effective antiviral treatment and presents a continuous risk to the host. The dormant viral genome during latent infection provides few therapeutic targets other than itself for antiviral drug development. This study demonstrates the clearance of latent Epstein–Barr virus genomes in a subpopulation of Burkitt’s lymphoma patient-derived cells with clustered regularly interspaced short palindromic repeat/Cas9 nuclease. Viral genome destruction leads to proliferation arrest and apoptosis in Epstein–Barr virus-infected cells, with no observed cytotoxicity to noninfected cells. Although many hurdles remain before this approach could be used in the clinic, this strategy may lead to a generalized approach to cure latent viral infections.
Cell separation using tilted-angle standing surface acoustic waves
Authors: Ding Xiaoyun , Peng Zhangli , Lin Sz-Chin Steven , Geri Michela , Li Sixing , Li Peng , Chen Yuchao , Dao Ming , Suresh Subra , Huang Tony Jun 
Published: August 2014

Significance
We have developed a unique approach for the separation of particles and biological cells through standing surface acoustic waves oriented at an optimum angle to the fluid flow direction in a microfluidic device. This experimental setup, optimized by systematic analyses, has been used to demonstrate effective separation based on size, compressibility, and mechanical properties of particles and cells. The potential of this method for biological–biomedical applications was demonstrated through the example of isolating MCF-7 breast cancer cells from white blood cells. The method offers a possible route for label-free particle or cell separation for many applications in research, disease diagnosis, and drug-efficacy assessment.
Lambda: the local aligner for massive biological data
Authors: Hauswedell Hannes , Singer Jochen , Reinert Knut 
Published: August 2014

Abstract
Motivation: Next-generation sequencing technologies produce unprecedented amounts of data, leading to completely new research fields. One of these is metagenomics, the study of large-size DNA samples containing a multitude of diverse organisms. A key problem in metagenomics is to functionally and taxonomically classify the sequenced DNA, to which end the well-known BLAST program is usually used. But BLAST has dramatic resource requirements at metagenomic scales of data, imposing a high financial or technical burden on the researcher. Multiple attempts have been made to overcome these limitations and present a viable alternative to BLAST.
Results: In this work we present Lambda, our own alternative for BLAST in the context of sequence classification. In our tests, Lambda often outperforms the best tools at reproducing BLAST’s results and is the fastest compared with the current state of the art at comparable levels of sensitivity.
Availability and implementation: Lambda was implemented in the SeqAn open-source C++ library for sequence analysis and is publicly available for download at http://www.seqan.de/projects/lambda.
Contact: hannes.hauswedell@fu-berlin.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Fiona: a parallel and automatic strategy for read error correction
Authors: Schulz Marcel H. , Weese David , Holtgrewe Manuel , Dimitrova Viktoria , Niu Sijia , Reinert Knut , Richard Hugues 
Published: August 2014

Abstract
Motivation: Automatic error correction of high-throughput sequencing data can have a dramatic impact on the amount of usable base pairs and their quality. It has been shown that the performance of tasks such as de novo genome assembly and SNP calling can be dramatically improved after read error correction. While a large number of methods specialized for correcting substitution errors as found in Illumina data exist, few methods for the correction of indel errors, common to technologies like 454 or Ion Torrent, have been proposed.
Results: We present Fiona, a new stand-alone read error–correction method. Fiona provides a new statistical approach for sequencing error detection and optimal error correction and estimates its parameters automatically. Fiona is able to correct substitution, insertion and deletion errors and can be applied to any sequencing technology. It uses an efficient implementation of the partial suffix array to detect read overlaps with different seed lengths in parallel. We tested Fiona on several real datasets from a variety of organisms with different read lengths and compared its performance with state-of-the-art methods. Fiona shows a constantly higher correction accuracy over a broad range of datasets from 454 and Ion Torrent sequencers, without compromise in speed.
Conclusion: Fiona is an accurate parameter-free read error–correction method that can be run on inexpensive hardware and can make use of multicore parallelization whenever available. Fiona was implemented using the SeqAn library for sequence analysis and is publicly available for download at http://www.seqan.de/projects/fiona.
Contact: mschulz@mmci.uni-saarland.de or hugues.richard@upmc.fr
Supplementary information: Supplementary data are available at Bioinformatics online.
FastHap: fast and accurate single individual haplotype reconstruction using fuzzy conflict graphs
Authors: Mazrouee Sepideh , Wang Wei 
Published: August 2014

Abstract
Motivation: Understanding exact structure of an individual’s haplotype plays a significant role in various fields of human genetics. Despite tremendous research effort in recent years, fast and accurate haplotype reconstruction remains as an active research topic, mainly owing to the computational challenges involved. Existing haplotype assembly algorithms focus primarily on improving accuracy of the assembly, making them computationally challenging for applications on large high-throughput sequence data. Therefore, there is a need to develop haplotype reconstruction algorithms that are not only accurate but also highly scalable.
Results: In this article, we introduce FastHap, a fast and accurate haplotype reconstruction approach, which is up to one order of magnitude faster than the state-of-the-art haplotype inference algorithms while also delivering higher accuracy than these algorithms. FastHap leverages a new similarity metric that allows us to precisely measure distances between pairs of fragments. The distance is then used in building the fuzzy conflict graphs of fragments. Given that optimal haplotype reconstruction based on minimum error correction is known to be NP-hard, we use our fuzzy conflict graphs to develop a fast heuristic for fragment partitioning and haplotype reconstruction.
Availability: An implementation of FastHap is available for sharing on request.
Contact: sepideh@cs.ucla.edu
Broad-Enrich: functional interpretation of large sets of broad genomic regions
Authors: Cavalcante Raymond G. , Lee Chee , Welch Ryan P. , Patil Snehal , Weymouth Terry , Scott Laura J. , Sartor Maureen A. 
Published: August 2014

AbstractMotivation: Functional enrichment testing facilitates the interpretation of Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data in terms of pathways and other biological contexts. Previous methods developed and used to test for key gene sets affected in ChIP-seq experiments treat peaks as points, and are based on the number of peaks associated with a gene or a binary score for each gene. These approaches work well for transcription factors, but histone modifications often occur over broad domains, and across multiple genes.Results: To incorporate the unique properties of broad domains into functional enrichment testing, we developed Broad-Enrich, a method that uses the proportion of each gene’s locus covered by a peak. We show that our method has a well-calibrated false-positive rate, performing well with ChIP-seq data having broad domains compared with alternative approaches. We illustrate Broad-Enrich with 55 ENCODE ChIP-seq datasets using different methods to define gene loci. Broad-Enrich can also be applied to other datasets consisting of broad genomic domains such as copy number variations.Availability and implementation: http://broad-enrich.med.umich.edu for Web version and R package.Contact: sartorma@umich.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Modeling DNA methylation dynamics with approaches from phylogenetics
Authors: Capra John A. , Kostka Dennis 
Published: August 2014

Abstract
Motivation: Methylation of CpG dinucleotides is a prevalent epigenetic modification that is required for proper development in vertebrates. Genome-wide DNA methylation assays have become increasingly common, and this has enabled characterization of DNA methylation in distinct stages across differentiating cellular lineages. Changes in CpG methylation are essential to cellular differentiation; however, current methods for modeling methylation dynamics do not account for the dependency structure between precursor and dependent cell types.
Results: We developed a continuous-time Markov chain approach, based on the observation that changes in methylation state over tissue differentiation can be modeled similarly to DNA nucleotide changes over evolutionary time. This model explicitly takes precursor to descendant relationships into account and enables inference of CpG methylation dynamics. To illustrate our method, we analyzed a high-resolution methylation map of the differentiation of mouse stem cells into several blood cell types. Our model can successfully infer unobserved CpG methylation states from observations at the same sites in related cell types (90% correct), and this approach more accurately reconstructs missing data than imputation based on neighboring CpGs (84% correct). Additionally, the single CpG resolution of our methylation dynamics estimates enabled us to show that DNA sequence context of CpG sites is informative about methylation dynamics across tissue differentiation. Finally, we identified genomic regions with clusters of highly dynamic CpGs and present a likely functional example. Our work establishes a framework for inference and modeling that is well suited to DNA methylation data, and our success suggests that other methods for analyzing DNA nucleotide substitutions will also translate to the modeling of epigenetic phenomena.
Availability and implementation: Source code is available at www.kostkalab.net/software.
Contact: tony.capra@vanderbilt.edu or kostka@pitt.edu
Alignment-free protein interaction network comparison
Authors: Ali Waqar , Rito Tiago , Reinert Gesine , Sun Fengzhu , Deane Charlotte M. 
Published: August 2014

Abstract
Motivation: Biological network comparison software largely relies on the concept of alignment where close matches between the nodes of two or more networks are sought. These node matches are based on sequence similarity and/or interaction patterns. However, because of the incomplete and error-prone datasets currently available, such methods have had limited success. Moreover, the results of network alignment are in general not amenable for distance-based evolutionary analysis of sets of networks. In this article, we describe Netdis, a topology-based distance measure between networks, which offers the possibility of network phylogeny reconstruction.
Results: We first demonstrate that Netdis is able to correctly separate different random graph model types independent of network size and density. The biological applicability of the method is then shown by its ability to build the correct phylogenetic tree of species based solely on the topology of current protein interaction networks. Our results provide new evidence that the topology of protein interaction networks contains information about evolutionary processes, despite the lack of conservation of individual interactions. As Netdis is applicable to all networks because of its speed and simplicity, we apply it to a large collection of biological and non-biological networks where it clusters diverse networks by type.
Availability and implementation: The source code of the program is freely available at http://www.stats.ox.ac.uk/research/proteins/resources.
Contact: w.ali@stats.ox.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Identifying transcription factor complexes and their roles
Authors: Will Thorsten , Helms Volkhard 
Published: August 2014

Abstract
Motivation: Eukaryotic gene expression is controlled through molecular logic circuits that combine regulatory signals of many different factors. In particular, complexation of transcription factors (TFs) and other regulatory proteins is a prevailing and highly conserved mechanism of signal integration within critical regulatory pathways and enables us to infer controlled genes as well as the exerted regulatory mechanism. Common approaches for protein complex prediction that only use protein interaction networks, however, are designed to detect self-contained functional complexes and have difficulties to reveal dynamic combinatorial assemblies of physically interacting proteins.
Results: We developed the novel algorithm DACO that combines protein–protein interaction networks and domain–domain interaction networks with the cluster-quality metric cohesiveness. The metric is locally maximized on the holistic level of protein interactions, and connectivity constraints on the domain level are used to account for the exclusive and thus inherently combinatorial nature of the interactions within such assemblies. When applied to predicting TF complexes in the yeast Saccharomyces cerevisiae, the proposed approach outperformed popular complex prediction methods by far. Furthermore, we were able to assign many of the predictions to target genes, as well as to a potential regulatory effect in agreement with literature evidence.
Availability and implementation: A prototype implementation is freely available at https://sourceforge.net/projects/dacoalgorithm/.
Contact: volkhard.helms@bioinformatik.uni-saarland.de
Supplementary information: Supplementary data are available at Bioinformatics online.
HubAlign: an accurate and efficient method for global alignment of protein–protein interaction networks
Authors: Hashemifar Somaye , Xu Jinbo 
Published: August 2014

Abstract
Motivation: High-throughput experimental techniques have produced a large amount of protein–protein interaction (PPI) data. The study of PPI networks, such as comparative analysis, shall benefit the understanding of life process and diseases at the molecular level. One way of comparative analysis is to align PPI networks to identify conserved or species-specific subnetwork motifs. A few methods have been developed for global PPI network alignment, but it still remains challenging in terms of both accuracy and efficiency.
Results: This paper presents a novel global network alignment algorithm, denoted as HubAlign, that makes use of both network topology and sequence homology information, based upon the observation that topologically important proteins in a PPI network usually are much more conserved and thus, more likely to be aligned. HubAlign uses a minimum-degree heuristic algorithm to estimate the topological and functional importance of a protein from the global network topology information. Then HubAlign aligns topologically important proteins first and gradually extends the alignment to the whole network. Extensive tests indicate that HubAlign greatly outperforms several popular methods in terms of both accuracy and efficiency, especially in detecting functionally similar proteins.
Availability: HubAlign is available freely for non-commercial purposes at http://ttic.uchicago.edu/∼hashemifar/software/HubAlign.zip
Contact: jinboxu@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.