bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-stage processing of category and variation information by entangled interactive mechanisms of peri-occipital and peri-frontal cortices
Authors: Karimi-Rouzbahani Hamid 
Published: January 2018

AbstractInvariant object recognition, which refers to the ability of precisely and rapidly recognizing objects in the presence of variations, has been a central question in human vision research. The general consensus is that the ventral and dorsal visual streams are the major processing pathways which undertake category and variation encoding in entangled layers. This overlooks the mounting evidence which support the role of peri-frontal areas in category encoding. These recent studies, however, have left open several aspects of visual processing in peri-frontal areas including whether these areas contributed only in active tasks, whether they interacted with peri-occipital areas or processed information independently and differently. To address these concerns, a passive EEG paradigm was designed in which subjects viewed a set of variation-controlled object images. Using multivariate pattern analysis, noticeable category and variation information were observed in occipital, parietal, temporal and prefrontal areas, supporting their contribution to visual processing. Using task specificity indices, phase and Granger causality analyses, three distinct stages of processing were identified which revealed transfer of information between peri-frontal and peri-occipital areas suggesting their parallel and interactive processing of visual information. A brain-plausible computational model supported the possibility of parallel processing mechanisms in peri-occipital and peri-frontal areas. These findings, while advocating previous results on the role of prefrontal areas in object recognition, extend their contribution from active recognition, in which peri-frontal to peri-occipital feedback mechanisms are activated, to the general case of object and variation processing, which is an integral part of visual processing and play role even during passive viewing.
A temporally dynamic Foxp3 autoregulatory transcriptional circuit controls the effector Treg programme
Authors: Bending David , Paduraru Alina , Prieto Martin Paz , Crompton Tessa , Ono Masahiro 
Published: January 2018

AbstractRegulatory T cells (Treg) are negative regulators of the immune response. Whilst thymic Treg generation is well studied, it is not known whether and how Foxp3 transcription is induced and regulated in the periphery during immune responses. Here we use Foxp3 Timer of cell kinetics and activity (Tocky) mice, which report real-time Foxp3 gene transcription by measuring the spontaneous maturation of Fluorescent Timer protein from Blue to Red fluorescence, to identify the flux of Foxp3-to Foxp3+ T cells within the periphery and analyse the real-time activity of Foxp3 transcription. Using a murine model of skin allergy, we show that both the flux of new Foxp3 expressors and the rate of Foxp3 transcription are increased at inflamed sites. These persistent dynamics of Foxp3 transcription determine the effector Treg programme, and are dependent on a Foxp3 autoregulatory transcriptional circuit, as evidenced by analysis of T cells lacking functional Foxp3 protein. Such reactive and persistent Foxp3 transcriptional activity controls the expression of coinhibitory molecules including CTLA-4 and effector-Treg signature genes. Using RNA-seq, we identify two groups of surface proteins based on their relationship to the temporal dynamics of Foxp3 transcription, and we show proof-of-principle for the manipulation of Foxp3 dynamics by immunotherapy: new Foxp3 flux is promoted by anti-TNFRII antibody, and high frequency Foxp3 expressors are depleted by anti-OX40 antibody. Collectively, our study dissects time-dependent mechanisms behind Foxp3-driven T cell regulation, and establishes the Foxp3-Tocky system as a tool to investigate the mechanisms behind T cell immunotherapies.
Functionally asymmetric motor neurons coordinate locomotion of Caenorhabditis elegans
Authors: Tolstenkov Oleg , Van der Auwera Petrus , Liewald Jana F. , Costa Wagner Steuer , Bazhanova Olga , Gemeinhard Tim , Bergs Amelie C. F. , Gottschalk Alexander 
Published: January 2018

SummaryInvertebrate nervous systems are valuable models for fundamental principles of the control of behavior. Ventral nerve cord (VNC) motor neurons in Caenorhabditis elegans represent one of the best studied locomotor circuits, with known connectivity and functional information about most of the involved neuron classes. However, for one of those, the AS motor neurons (AS MNs), no physiological data is available. Combining specific expression and selective illumination, we precisely targeted AS MNs by optogenetics and addressed their role in the locomotion circuit. After photostimulation, AS MNs induce currents in post-synaptic body wall muscles (BWMs), exhibiting an initial asymmetry of excitatory output. This may facilitate complex regulatory motifs for adjusting direction during navigation. By behavioral and photo-inhibition experiments, we show that AS MNs contribute to propagation of the antero-posterior body wave during locomotion. By Ca2+-imaging in AS MNs and in their synaptic partners, we also reveal that AS MNs play a role in mediating forward and backward locomotion by integrating activity of premotor interneurons (PINs), as well as in coordination of the dorso-ventral body wave. AS MNs do not exhibit pacemaker properties, but potentially gate VNC central pattern generators (CPGs), as indicated by ceasing of locomotion when AS MNs are hyperpolarized. AS MNs provide positive feedback to the PIN AVA via gap junctions, a feature found also in other locomotion circuits. In sum, AS MNs have essential roles in coordinating locomotion, combining several functions, and emphasizing the compressed nature of the C. elegans nervous system in comparison to higher animals.HighlightsA class of motor neurons with unidentified function – AS cholinergic motor neurons - was characterized in C. elegans.AS neurons show asymmetry in both input and output and are specialized in coordination of dorso-ventral undulation bends.AS neurons mediate antero-posterior propagation of the undulatory body wave during locomotion.AS neurons integrate signals for forward and reverse locomotion from premotor interneurons and may gate ventral nerve cord central pattern generators (CPGs) via gap junctions.
TOGGLe, a flexible framework for easily building complex workflows and performing robust large-scale NGS analyses
Authors: Tranchant-Dubreuil Christine , Ravel Sébastien , Monat Cécile , Sarah Gautier , Diallo Abdoulaye , Helou Laura , Dereeper Alexis , Tando Ndomassi , Orjuela-Bouniol Julie , Sabot François 
Published: January 2018

ABSTRACTThe advent of NGS has intensified the need for robust pipelines to perform high-performance automated analyses. The required softwares depend on the sequencing method used to produce raw data (e.g. Whole genome sequencing, Genotyping By Sequencing, RNASeq) as well as the kind of analyses to carry on (GWAS, population structure, differential expression). These tools have to be generic and scalable, and should meet the biologists needs.Here, we present the new version of TOGGLe (Toolbox for Generic NGS Analyses), a simple and highly flexible framework to easily and quickly generate pipelines for large-scale second- and third-generation sequencing analyses, including multi-sample and multi-threading support. TOGGLe is a workflow manager designed to be as effortless as possible to use for biologists, so the focus can remain on the analyses. Pipelines are easily customizable and supported analyses are reproducible and shareable. TOGGLe is designed as a generic, adaptable and fast evolutive solution, and has been tested and used in large-scale projects on various organisms. It is freely available at http://toggle.southgreen.fr/, under the GNU GPLv3/CeCill-C licenses) and can be deployed onto HPC clusters as well as on local machines.
Time-scale separation and stochasticity conspire to impact phenotypic dynamics in the canonical and inverted Bacillus subtilis core genetic regulation circuits
Authors: Hao Lijie , Yang Zhuoqin , Turcotte Marc 
Published: January 2018

AbstractIn this work, we study two seemingly unrelated aspects of core genetic nonlinear dynamical control of the competence phenotype in Bacillus subtilis, a common Gram-positive bacterium living in the soil. We focus on hitherto unchartered aspects of the dynamics by exploring the effect of time scale separation between transcription and translation and, as well, the effect of intrinsic molecular stochasticity. We consider these aspects of regulatory control as two possible evolutionary handles. Hence, using theory and computations, we study how the onset of oscillations breaks the excitability-based competence phenotype in two topologically close evolutionary competing circuits: the canonical “wild-type” regulation circuit selected by Evolution and, the indirect-feedback inverted circuit that failed to be selected by Evolution, as was shown elsewhere, due to dynamical reasons.
AGO CLIP reveals an activated network for acute regulation of brain glutamate homeostasis after ischemic stroke
Authors: Kobayashi Mariko , Benakis Corinne , Anderson Corey , Moore Michael J. , Poon Carrie , Uekawa Ken , Dyke Jonathan P. , Fak John J. , Mele Aldo , Park Christopher Y. , Zhou Ping , Anrather Josef , Iadecola Costantino , Darnell Robert B. 
Published: January 2018

ABSTRACTPost-transcriptional regulation by miRNAs is essential for complex molecular responses to physiological insult and disease. Although many disease-associated miRNAs are known, their global targets and culminating network effects on pathophysiology remain poorly understood. We applied AGO CLIP to systematically elucidate altered miRNA-target interactions in brain following ischemia/reperfusion (I/R) injury. Among 1,190 identified, most prominent was the cumulative loss of target regulation by miR-29 family members. Integration of translational and time-course RNA profiles revealed a dynamic mode of miR-29 target de-regulation, led by acute translational activation and later increase in RNA levels, allowing rapid proteomic changes to take effect. These functional regulatory events rely on canonical and non-canonical miR-29 binding and engage glutamate reuptake signals to control local glutamate levels. These results uncover a miRNA target network that acts acutely to maintain brain homeostasis after ischemic stroke.
Causal Discovery of Feedback Networks with Functional Magnetic Resonance Imaging
Authors: Sanchez-Romero R , Ramsey J.D. , Zhang K. , Glymour M. R. K , Huang B , Glymour C. 
Published: January 2018

AbstractWe test the adequacies of several proposed and two new statistical methods for recovering the causal structure of systems with feedback that generate noisy time series closely matching real BOLD time series. We compare: an adaptation for time series of the first correct method for recovering the structure of cyclic linear systems; multivariate Granger causal regression; the GIMME algorithm; the Ramsey et al. non-Gaussian methods; two non-Gaussian methods proposed by Hyv¨arinen and Smith; a method due to Patel, et al.; and the GlobalMIT algorithm. We introduce and also compare two new methods, the Fast Adjacency Skewness (FASK) and Two-Step, which exploit non-Gaussian features of the BOLD signal in different ways. We give theoretical justifications for the latter two algorithms. Our test models include feedback structures with and without direct feedback (2-cycles), excitatory and inhibitory feedback, models using experimentally determined structural connectivities of macaques, and empirical resting state and task data. We find that averaged over all of our simulations, including those with 2-cycles, several of these methods have a better than 80% orientation precision (i.e., the probability a directed edge is in the true generating structure given that a procedure estimates it to be so) and the two new methods also have better than 80% recall (probability of recovering an orientation in the data generating model). Recovering inhibitory direct feedback loops between two regions is especially challenging.
Action-outcome knowledge dissociates from behavior in obsessive-compulsive disorder following contingency degradation
Authors: Vaghi Matilde M. , Cardinal Rudolf N. , Apergis-Schoute Annemieke M. , Fineberg Naomi A. , Sule Akeem , Robbins Trevor W. 
Published: January 2018

ABSTRACTGoal-directed and habitual systems orchestrate action control. In disorders of compulsivity, their interplay seems disrupted and actions persist despite being inappropriate and without relationship to the overall goal. We manipulated action–outcome contingency to test whether actions are goal-directed or habitual in obsessive-compulsive disorder (OCD), the prototypical disorder of compulsivity, in which prominent theories have suggested that dysfunctional beliefs underlie the necessity for compulsive actions.OCD patients responded more than controls when an action was causally less related to obtaining an outcome, indicating excessive habitual responding. Patients showed intact explicit action–outcome knowledge but this was not translated normally into behavior; the relationship between causality judgment and responding was blunted. OCD patients’ actions were dissociated from explicit action-outcome knowledge, providing experimental support for the ego-dystonic nature of OCD and suggesting that habitual action is not sustained by dysfunctional belief.
No Evidence for Systematic White Matter Correlates of Dyslexia: An Activation Likelihood Estimation Meta-Analysis
Authors: Moreau David , Stonyer Josephine E. , McKay Nicole S. , Waldie Karen E. 
Published: January 2018

AbstractDyslexia is a prevalent neurodevelopmental disorder, characterized by reading and spelling difficulties. Beyond the behavioral and functional correlates of this condition, a growing number of studies have explored structural differences between individuals with dyslexia and typically developing individuals. To date, findings remain disparate – some studies suggest differences in fractional anisotropy (FA), an indirect measure of white matter integrity, whereas others do not identify significant disparities. Here, we synthesized the existing literature on this topic by conducting a meta-analysis of Diffusion Tensor Imaging (DTI) studies investigating white matter correlates of dyslexia via voxel-based analyses (VBA) of FA. Our results showed no reliable clusters underlying differences between dyslexics and typical individuals, after correcting for multiple comparisons (false discovery rate correction). Because group comparisons might be too coarse to yield subtle differences, we further explored differences in FA as a function of reading ability, measured on a continuous scale. Consistent with our initial findings, reading ability was not associated with reliable differences in white matter integrity. These findings nuance the current view of profound, structural differences underlying reading ability and its associated disorders, and suggest that their neural correlates might be more subtle than previously thought.
GtTR: Bayesian estimation of absolute tandem repeat copy number using sequence capture and high throughput sequencing
Authors: Ganesamoorthy Devika , Cao Minh Duc , Duarte Tania , Chen Wenhan , Coin Lachlan 
Published: January 2018

ABSTRACTBackgroundTandem repeats comprise significant proportion of the human genome including coding and regulatory regions. They are highly prone to repeat number variation and nucleotide mutation due to their repetitive and unstable nature, making them a major source of genomic variation between individuals. Despite recent advances in high throughput sequencing, analysis of tandem repeats in the context of complex diseases is still hindered by technical limitations.MethodsWe report a novel targeted sequencing approach, which allows simultaneous analysis of hundreds of repeats. We developed a Bayesian algorithm, namely – GtTR - which combines information from a reference long-read dataset with a short read counting approach to genotype tandem repeats at population scale. PCR sizing analysis was used for validation.ResultsWe used a PacBio long-read sequenced sample to generate a reference tandem repeat genotype dataset with on average 13% absolute deviation from PCR sizing results. Using this reference dataset GtTR generated estimates of VNTR copy number with accuracy within 95% high posterior density (HPD) intervals of 68% and 83% for capture sequence data and 200X WGS data respectively, improving to 87% and 94% with use of a PCR reference. We show that the genotype resolution increases as a function of depth, such that the median 95% HPD interval lies within 25%, 14%, 12% and 8% of the its midpoint copy number value for 30X, 200X WGS, 395X and 800X capture sequence data respectively. We validated nine targets by PCR sizing analysis and genotype estimates from sequencing results correlated well with PCR results.ConclusionsThe novel genotyping approach described here presents a new cost-effective method to explore previously unrecognized class of repeat variation in GWAS studies of complex diseases at the population level. Further improvements in accuracy can be obtained by improving accuracy of the reference dataset.
Using paired serology and surveillance data to quantify dengue transmission and control during a large outbreak in Fiji
Authors: Kucharski Adam J , Kama Mike , Watson Conall H , Aubry Maite , Funk Sebastian , Henderson Alasdair D , Brady Oliver J , Vanhomwegen Jessica , Manuguerra Jean-Claude , Lau Colleen L , Edmunds W John , Aaskov John , Nilles Eric J , Cao-Lormeau Van-Mai , Hue Stephane , Hibberd Martin 
Published: January 2018

AbstractDengue is a major health burden, but it can be challenging to examine transmission dynamics and evaluate control measures because outbreaks depend on multiple factors, including human population structure, prior immunity and climate. We combined population-representative paired sera collected before and after the major 2013/14 dengue-3 outbreak in Fiji with surveillance data to determine how such factors influence dengue virus transmission and control in island settings. Our results suggested the 10-19 year-old age group had the highest risk of acquiring infection, but we did not find strong evidence that other demographic or environmental risk factors were linked to seroconversion. Mathematical modelling showed that temperature-driven variation in transmission and herd immunity could not fully explain observed dynamics. However, there was evidence of an additional reduction in transmission coinciding with a vector clean-up campaign, which may have contributed to the decline in cases and prevented transmission continuing into the following season.
Edge Factors: Scientific Frontier Positions of Nations
Authors: Packalen Mikko 
Published: January 2018

AbstractA key decision in scientific work is whether to build on novel or well-established ideas. Because exploiting new ideas is often harder than more conventional science, novel work can be especially dependent on interactions with colleagues, the training environment, and ready access to potential collaborators. Location may thus influence the tendency to pursue work that is close to the edge of the scientific frontier in the sense that it builds on recent ideas. We calculate for each nation its position relative to the edge of the scientific frontier by measuring its propensity to build on relatively new ideas in biomedical research. Text analysis of 20+ million publications shows that the United States and South Korea have the highest tendencies for novel science. China has become a leader in favoring newer ideas when working with basic science ideas and research tools, but is still slow to adopt new clinical ideas. Many locations remain far behind the leaders in terms of their tendency to work with novel ideas, indicating that the world is far from flat in this regard.
Improving new product development (NPD) process by analyzing failure cases
Authors: Kim Yeon-Hak , Park Sun-Woong , Sawng Yeong-Wha 
Published: January 2018

Purpose
The purpose of this study is to develop an appropriate new product development (NPD) process of Company “T”, a medium-sized firm, by analyzing the existing NPD process and failure cases of the Company.

Design/methodology/approach
The proposed research framework is as follows: first, prospective studies of the NPD process are performed using the existing literature and preliminary references; second, comparative analysis between the current processes and a NPD process is performed; third, phase-based evaluations upon failed product cases are conducted with a NPD process so as to identify the abridged steps and root-causes of failures; finally, renewed priorities are set forth by utilizing the analytic hierarchy process analysis and questionnaire analysis upon the above identified causes of failures.

Findings
The resulting accomplishments include the establishment of NPD processes that resonates with the current states of Company “T”, which, in turn, ensures the increase of efficiency, the decrease in development duration and the strategy of capacity-concentration and priority-selection.

Originality/value
As Company “T”’s development process is outdated and products are developed without adequate market information research and feasibility analysis, the percentage of failed development project is as high as 87 per cent. Thus, this study aims to develop an appropriate NPD process of Company “T” by analyzing the existing NPD process and failure cases of the Company.
Creating ventures: decision factors in new venture creation
Authors: Kirkley William W. 
Published: January 2018

Purpose
The purpose of this pilot study was to identify the key factors that influence the decisions of entrepreneurs who are considering the creation of a new venture. The pilot was conducted to explore the cognitive antecedents of entrepreneurial decision-making and whether specific factors contribute to the decision to create a new venture.

Design/methodology/approach
The study utilised an inductive and interpretive research design within a constructivist paradigm. The sample comprised entrepreneurs situated in a business incubation unit who engaged in a series of semi-structured interviews. The results of this study will be used to refine the questions asked in preparation for a larger sample using in-depth interviews with identified entrepreneurs. The resulting narrative in this pilot was subjected to discourse analysis and is categorised into relevant themes.

Findings
The findings in this pilot study reveal that factors such as technological advancement, market opportunity, competition, customer demand and prevailing market conditions have a significant influence on the decision-making process involved in creating a new venture.

Research limitations/implications
Although the pilot has identified several factors in entrepreneurial decision-making, further work will be needed in the research design to be able to expose the cognitive processes associated with each factor. The aim is to identify the common cognitive characteristics associated with thinking through the decision to create a new venture with a much larger sample of entrepreneurs.

Originality/value
The value of this research lies in exploring and developing a better understanding of the antecedent cognitive processes used by entrepreneurs for identifying unique, innovative new ideas and converting them into exploitable products or services through new venture creation.