bluuebunny/crossref_metadata_2025_split huggingface dataset:
accuMUlate: A mutation caller designed for mutation accumulation experiments
Authors: Winter David J. , Wu Steven H. , Howell Abigail A. , Azevedo Ricardo B. R. , Zufall Rebecca A. , Cartwright Reed A. 
Published: September 2017

AbstractMotivationMutation accumulation (MA) is the most widely used method for directly studying the effects of mutation. Modern sequencing technologies have led to an increased interest in MA experiments. By sequencing whole genomes from MA lines, researchers can directly study the rate and molecular spectra of spontaneous mutations and use these results to understand how mutation contributes to biological processes. At present there is no software designed specifically for identifying mutations from MA lines. Studies that combine MA with whole genome sequencing use custom bioinformatic pipelines that implement heuristic rules to identify putative mutations.ResultsHere we describeaccuMUlate, a program that is designed to detect mutations from MA experiments.accuMUlateimplements a probabilistic model that reflects the design of a typical MA experiments while being flexible enough to accommodate properties unique to any particular experiment. For each putative mutation identified from this modelaccuMUlatecalculates a set of summary statistics that can be used to filter sites that may be false positives. A companion tool,denominate, can be used to apply filtering rules based on these statistics to simulated mutations and thus identify the number of callable sites per sample.AvailabilitySource code and releases available fromhttps://github.com/dwinter/accuMUlate.
Measuring the reproducibility and quality of Hi-C data
Authors: Yardımcı Galip Gürkan , Ozadam Hakan , Sauria Michael E.G. , Ursu Oana , Yan Koon-Kiu , Yang Tao , Chakraborty Abhijit , Kaul Arya , Lajoie Bryan R. , Song Fan , Zhang Ye , Ay Ferhat , Gerstein Mark , Kundaje Anshul , Li Qunhua , Taylor James , Yue Feng , Dekker Job , Noble William S. 
Published: September 2017

AbstractHi-C is currently the most widely used assay to investigate the 3D organization of the genome and to study its role in gene regulation, DNA replication, and disease. However, Hi-C experiments are costly to perform and involve multiple complex experimental steps; thus, accurate methods for measuring the quality and reproducibility of Hi-C data are essential to determine whether the output should be used further in a study. Using real and simulated data, we profile the performance of several recently proposed methods for assessing reproducibility of population Hi-C data, including HiCRep, GenomeDISCO, HiC-Spector and QuASAR-Rep. By explicitly controlling noise and sparsity through simulations, we demonstrate the deficiencies of performing simple correlation analysis on pairs of matrices, and we show that methods developed specifically for Hi-C data produce better measures of reproducibility. We also show how to use established (e.g., ratio of intra to interchromosomal interactions) and novel (e.g., QuASAR-QC) measures to identify low quality experiments. In this work, we assess reproducibility and quality measures by varying sequencing depth, resolution and noise levels in Hi-C data from 13 cell lines, with two biological replicates each, as well as 176 simulated matrices. Through this extensive validation and benchmarking of Hi-C data, we describe best practices for reproducibility and quality assessment of Hi-C experiments. We make all software publicly available athttp://github.com/kundajelab/3DChromatin_ReplicateQCto facilitate adoption in the community.
Single synapses control mossy cell firing
Authors: Drakew Alexander , Maier Urban , Tippmann Anja , Frotscher Michael 
Published: September 2017

AbstractThe function of mossy cells (MCs) in the dentate gyrus has remained elusive. Here we determined the functional impact of single mossy fibre (MF) synapses on MC firing in mouse entorhino-hippocampal slice cultures. We stimulated single MF boutons and recorded Ca2+transients in the postsynaptic spine and unitary excitatory postsynaptic potentials (EPSPs) at the MC soma. Synaptic responses to single presynaptic stimuli varied strongly between different MF synapses, even if they were located on the same MC dendrite. Synaptic strengths ranged from subthreshold EPSPs to direct postsynaptic action potential (AP) generation. Induction of synaptic plasticity at these individual MF synapses resulted in potentiation or depression depending on the initially encountered synaptic state, indicating that synaptic transmission at MF synapses on MCs is determined by their previous functional history. With these unique functional properties MF-MC synapses control MC firing individually thereby enabling modulation of the dentate network by single granule cells.
Generation and validation of homozygous fluorescent knock-in cells using CRISPR/Cas9 genome editing
Authors: Koch Birgit , Nijmeijer Bianca , Kueblbeck Moritz , Cai Yin , Walther Nike , Ellenberg Jan 
Published: September 2017

AbstractGene tagging with fluorescent proteins is essential to investigate the dynamic properties of cellular proteins. CRISPR/Cas9 technology is a powerful tool for inserting fluorescent markers into all alleles of the gene of interest (GOI) and permits functionality and physiological expression of the fusion protein. It is essential to evaluate such genome-edited cell lines carefully in order to preclude off-target effects caused by either (i) incorrect insertion of the fluorescent protein, (ii) perturbation of the fusion protein by the fluorescent proteins or (iii) non-specific genomic DNA damage by CRISPR/Cas9. In this protocol1, we provide a step-by-step description of our systematic pipeline to generate and validate homozygous fluorescent knock-in cell lines.We have used the paired Cas9D10A nickase approach to efficiently insert tags into specific genomic lociviahomology-directed repair with minimal off-target effects. It is time- and cost-consuming to perform whole genome sequencing of each cell clone. Therefore, we have developed an efficient validation pipeline of the generated cell lines consisting of junction PCR, Southern Blot analysis, Sanger sequencing, microscopy, Western blot analysis and live cell imaging for cell cycle dynamics. This protocol takes between 6-9 weeks. Using this protocol, up to 70% of the targeted genes can be tagged homozygously with fluorescent proteins and result in physiological levels and phenotypically functional expression of the fusion proteins.Editorial SummaryThis protocol provides a detailed workflow describing how to insert fluorescent markers into all alleles of a gene of interest using CRISPR/Cas 9 technology and how to generate and validate homozygous fluorescent knock-in cell lines.
Cortical Connectivity In A Macaque Model Of Congenital Blindness
Authors: Magrou Loïc , Barone Pascal , Markov Nikola T. , Killackey Herbert , Giroud Pascale , Berland Michel , Knoblauch Kenneth , Dehay Colette , Kennedy Henry 
Published: September 2017

Abstract:Brain-mapping of the congenitally blind human reveals extensive plasticity(1). The visual cortex of the blind has been observed to support higher cognitive functions including language and numerical processing(2, 3). This functional shift is hypothesized to reflect a metamodal cortical function, where computations are defined by the local network. In the case of developmental deafferentation, local circuits are considered to implement higher cognitive functions by accommodating diverse long-distance inputs(4–7). However, the extent to which visual deprivation triggers a reorganization of the large-scale network in the cortex is still controversial(8). Here we show that early prenatal ablation of the retina, an experimental model of anophthalmia in macaque, leads to a major reduction of area V1 and the creation of a default extrastriate cortex (DEC)(9, 10). Anophthalmic and normal macaques received retrograde tracer injections in DEC, as well as areas V2 and V4 post-natally. This revealed a six-fold expansion of the spatial extent of local connectivity in the DEC and a surprisingly high location of the DEC derived from a computational model of the cortical hierarchy(11). In the anophthalmic the set of areas projecting to the DEC, area V2 and V4 does not differ from that of normal adult controls, but there is a highly significant increase in the relative cumulative weight of the ventral stream areas input to the early visual areas. These findings show that although occupying the territory that would have become primary visual cortex the DEC exhibits features of a higher order area, thus reflecting a combination of intrinsic and extrinsic factors on cortical specification. Understanding the interaction of these contributing factors will shed light on cortical plasticity during primate development and the neurobiology of blindness.
A method for allocating low-coverage sequencing resources by targeting haplotypes rather than individuals
Authors: Ros-Freixedes Roger , Gonen Serap , Gorjanc Gregor , Hickey John M 
Published: September 2017

AbstractBackgroundThis paper describes a heuristic method for allocating low-coverage sequencing resources by targeting haplotypes rather than individuals. Low-coverage sequencing assembles high-coverage sequence information for every individual by accumulating data from the genome segments that they share with many other individuals into consensus haplotypes. Deriving the consensus haplotypes accurately is critical for achieving a high phasing and imputation accuracy. In order to enable accurate phasing and imputation of sequence information for the whole population we allocate the available sequencing resources among individuals with existing phased genomic data by targeting the sequencing coverage of their haplotypes.ResultsOur method, called AlphaSeqOpt, prioritizes haplotypes using a score function that is based on the frequency of the haplotypes in the sequencing set relative to the target coverage. AlphaSeqOpt has two steps: (1) selection of an initial set of individuals by iteratively choosing the individuals that have the maximum score conditional to the current set, and (2) refinement of the set through several rounds of exchanges of individuals. AlphaSeqOpt is very effective for distributing a fixed amount of sequencing resources evenly across haplotypes, which results in a reduction of the proportion of haplotypes that are sequenced below the target coverage. AlphaSeqOpt can provide a greater proportion of haplotypes sequenced at the target coverage by sequencing less individuals, as compared with other methods that use a score function based on the haplotypes population frequency. A refinement of the initially selected set can provide a larger more diverse set with more unique individuals, which is beneficial in the context of low-coverage sequencing. We extend the method with an approach to filter rare haplotypes based on their flanking haplotypes, so that only those that are likely to derive from a recombination event are targeted.ConclusionsWe present a method for allocating sequencing resources so that a greater proportion of haplotypes are sequenced at a coverage that is sufficiently high for population-based imputation with low-coverage sequencing. The haplotype score function, the refinement step, and the new approach of filtering rare haplotypes make AlphaSeqOpt more effective for that purpose than methods reported previously for reducing sequencing redundancy.
Phytophthora palmivora establishes tissue-specific intracellular infection structures in the earliest divergent land plant lineage
Authors: Carella Philip , Gogleva Anna , Tomaselli Marta , Alfs Carolin , Schornack Sebastian 
Published: September 2017

ABSTRACTThe expansion of plants onto land was a formative event that brought forth profound changes to the Earth’s geochemistry and biota. Filamentous eukaryotic microbes developed the ability to colonize plant tissues early during the evolution of land plants, as demonstrated by intimate symbiosis-like associations in >400 million-year-old fossils. However, the degree to which filamentous microbes establish pathogenic interactions with early divergent land plants is unclear. Here, we demonstrate that the broad host-range oomycete pathogenPhytophthora palmivoracolonizes liverworts, the earliest divergent land plant lineage. We show thatP. palmivoraestablishes a complex tissue-specific interaction withMarchantia polymorpha, where it completes a full infection cycle within air chambers of the dorsal photosynthetic layer. Remarkably,P. palmivorainvaginatesM. polymorphacells with haustoria-like structures that accumulate host cellular trafficking machinery and the membrane-syntaxin MpSYP13B but not the related MpSYP13A. Our results indicate that the intracellular accommodation of filamentous microbes is an ancient plant trait that is successfully exploited by pathogens likeP. palmivora.
Formation of functional, non-amyloidogenic fibres by recombinantBacillus subtilisTasA
Authors: Erskine Elliot , Morris Ryan J , Schor Marieke , Earl Chris , Gillespie Rachel M. C. , Bromley Keith , Sukhodub Tetyana , Clark Lauren , Fyfe Paul K. , Serpell Louise C. , Stanley-Wall Nicola R. , MacPhee Cait E. 
Published: September 2017

AbstractBacterial biofilms are communities of microbial cells encased within a self-produced polymeric matrix. In theBacillus subtilisbiofilm matrix the extracellular fibres of TasA are essential. Here a recombinant expression system allows interrogation of TasA, revealing that monomeric and fibre forms of TasA have identical secondary structure, suggesting that fibrous TasA is a linear assembly of globular units. Recombinant TasA fibres form spontaneously, and share the biological activity of TasA fibres extracted fromB. subtilis, whereas a TasA variant restricted to a monomeric form is inactive and subjected to extracellular proteolysis. The biophysical properties of both native and recombinant TasA fibres indicate that they are not functional amyloid-like fibres. A gel formed by TasA fibres can recover after physical shear force, suggesting that the biofilm matrix is not static and that these properties may enableB. subtilisto remodel its local environment in response to external cues. Using recombinant fibres formed by TasA orthologues we uncover species variability in the ability of heterologous fibres to cross-complement theB. subtilis tasAdeletion. These findings are indicative of specificity in the biophysical requirements of the TasA fibres across different species and/or reflect the precise molecular interactions needed for biofilm matrix assembly.ContributionsConceived and designed the experiments: CE, EE, RG, CEM, RJM, MS, NSW; Performed the experiments: KB, LC, CE, EE, PKF, RG, CEM, RJM, MS, TS; Contributed new analytical tools: CE, EE, RG, TS; Analysed the data: CE, EE, CEM, RJM, MS, LCS, NSW; Wrote the paper: EE, RJM, CEM, MS, NSW.
Assessing robustness against potential publication bias in coordinate based fMRI meta-analyses using the Fail-Safe N
Authors: Acar Freya , Seurinck Ruth , Eickhoff Simon B. , Moerkerke Beatrijs 
Published: September 2017

AbstractThe importance of integrating research findings is incontrovertible and coordinate based meta-analyses have become a popular approach to combine results of fMRI studies when only peaks of activation are reported. Similar to classical meta-analyses, coordinate based meta-analyses may be subject to different forms of publication bias which impacts results and possibly invalidates findings. We develop a tool that assesses the robustness to potential publication bias on cluster level. We investigate the possible influence of the file-drawer effect, where studies that do not report certain results fail to get published, by determining the number of noise studies that can be added to an existing fMRI meta-analysis before the results are no longer statistically significant. In this paper we illustrate this tool through an example and test the effect of several parameters through extensive simulations. We provide an algorithm for which code is freely available to generate noise studies and enables users to determine the robustness of meta-analytical results.
Conservation of preparatory neural events regardless of how movement is initiated
Authors: Lara Antonio H. , Elsayed Gamaleldin F. , Cunningham John P. , Churchland Mark M. 
Published: September 2017

AbstractVoluntary movement is believed to be preceded by a preparatory stage. Evidence arises from experiments where a delay separates instruction and execution cues. While this sequence emulates some real-world situations (e.g., swatting a fly upon landing) movements are commonly made at a moment of one’s choosing (reaching for a coffee cup) or are made reactively (intercepting a falling cup). To ascertain whether neural events are conserved across such contexts, we examined motor cortex population-level responses in monkeys when reaches were initiated either after an imposed delay, at a self-chosen time, or reactively with very low latency. We found that the same preparatory and movement-related events were conserved. However, preparation was temporally flexible and could be remarkably brief. Our findings support the existing hypothesis that preparation is an obligatory stage that achieves a consistent state prior to movement. Yet our results reveal that preparation can unfold more rapidly than previously supposed.
Adaptive finite element method for eigensolutions of regular second and fourth order Sturm-Liouville problems via the element energy projection technique
Authors: Yuan Si , Ye Kangsheng , Wang Yongliang , Kennedy David , Williams Frederic W. 
Published: September 2017

Purpose
The purpose of this paper is to present a numerically adaptive finite element (FE) method for accurate, efficient and reliable eigensolutions of regular second- and fourth-order Sturm–Liouville (SL) problems with variable coefficients.

Design/methodology/approach
After the conventional FE solution for an eigenpair (i.e. eigenvalue and eigenfunction) of a particular order has been obtained on a given mesh, a novel strategy is introduced, in which the FE solution of the eigenproblem is equivalently viewed as the FE solution of an associated linear problem. This strategy allows the element energy projection (EEP) technique for linear problems to calculate the super-convergent FE solutions for eigenfunctions anywhere on any element. These EEP super-convergent solutions are used to estimate the FE solution errors and to guide mesh refinements, until the accuracy matches user-preset error tolerance on both eigenvalues and eigenfunctions.

Findings
Numerical results for a number of representative and challenging SL problems are presented to demonstrate the effectiveness, efficiency, accuracy and reliability of the proposed method.

Research limitations/implications
The method is limited to regular SL problems, but it can also solve some singular SL problems in an indirect way.

Originality/value
Comprehensive utilization of the EEP technique yields a simple, efficient and reliable adaptive FE procedure that finds sufficiently fine meshes for preset error tolerances on eigenvalues and eigenfunctions to be achieved, even on problems which proved troublesome to competing methods. The method can readily be extended to vector SL problems.
The relationship between innovation and total quality management and the innovation effects on organizational performance
Authors: Antunes Marina Godinho , Quirós Joaquín Texeira , Justino Maria do Rosário Fernandes 
Published: September 2017

PurposeThe purpose of this paper is to analyze the relationship between innovation and total quality management (TQM), and also to identify the effects of innovation on organizational performance. This research proposes a conceptual model that intends to study several research hypotheses.Design/methodology/approachThe data were obtained through an online questionnaire, sent to small- and medium-sized Portuguese companies, having being conducted the study based on responses received from 287 valid questionnaires, and using a multivariate statistical analysis for statistical development.FindingsThe findings indicate that companies that adopt strategies of process innovation get improvements in their performance, both operationally and financially, while product innovation only provides improvements in the financial performance of organizations. It was also found that TQM practices encourage the definition of innovation strategies of products and processes. On the other hand, it was found that only companies that adopt innovation strategies of their processes promote the adoption of TQM practices, and there is a statistically significant relationship between product innovation and the implementation of TQM practices.Originality/valueThis research analyzed the dimensions studied in different aspects. It considered product innovation and process innovation, and with respect to performance, this dimension was analyzed through two different perspectives, namely, financial performance and operational performance. This research also provides a particular contribution to the literature with the analysis of the interdependencies between innovation and TQM in small- and medium-sized Portuguese companies.
Lean Six Sigma for public sector organizations: is it a myth or reality?
Authors: Antony Jiju , Rodgers Bryan , Cudney Elizabeth A. 
Published: September 2017

Purpose
Lean Six Sigma (LSS) as a process excellence has been widely adopted in both manufacturing and service organizations; however, its application in the public sector has not been widely explored. Is LSS still a myth or reality in our public sector organizations? The purpose of this paper is to make an attempt to debate about the use of LSS and its potential applications in the public sector context.

Design/methodology/approach
The initial approach is to critically evaluate the role of LSS in various public sector contexts, followed by showcasing four case studies from four different public sector settings: higher education, police service, public hospital and local government.

Findings
LSS methodology can be embraced by all public sector organizations to create efficient and effective processes to provide enhanced customer experience and value at reduced operational costs.

Research limitations/implications
This paper seeks to contribute to and broaden the limited body of evidence of the applicability of LSS to public sector organizations and identifies areas for further research and review.

Practical implications
LSS will continue to grow across many public sector organizations in Europe and other parts of the world over the forthcoming years. However, what will eventually determine if LSS is viewed by public sector organizations as just a passing management fad or not largely depends on the leadership and success of its execution. If LSS is deployed in its true sense across the public sector organizations at a global level, the hard cash savings generated can reach several billions.

Originality/value
The paper yields an immense value to both research scholars and practitioners who are engaged in the introduction of LSS as a business process improvement strategy to achieve and sustain competitive advantage. Moreover, this paper makes an attempt to dispel the myth of LSS which have been quite prevalent in many public sector organizations around us today.