bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building online genomics applications using BioPyramid
Authors: Stephenson Liam , Wakeham Yoshua , Seidenman Nick , Choi Jarny 
Published: March 2018

Abstract

Summary
BioPyramid is a Python package, which serves as a scaffold for building an online application for the exploration of gene expression data. It is designed for bioinformaticians wishing to quickly share transformed data and interactive analyses with collaborators. Current R-based tools similarly address the need to quickly share ‘omics’-data in an exploratory format, but these are generally small-scale, single-dataset solutions. Biopyramid is written in Python pyramid framework and scalable to address longer-term or more complex projects. It contains a number of components designed to reduce the time and effort in building such an application from scratch, including gene annotation, dataset models and visualization tools.

Availability and implementation
Freely available at http://github.com/jarny/biopyramid. Implemented in python and javascript.
MechRNA: prediction of lncRNA mechanisms from RNA–RNA and RNA–protein interactions
Authors: Gawronski Alexander R , Uhl Michael , Zhang Yajia , Lin Yen-Yi , Niknafs Yashar S , Ramnarine Varune R , Malik Rohit , Feng Felix , Chinnaiyan Arul M , Collins Colin C , Sahinalp S Cenk , Backofen Rolf 
Published: March 2018

Abstract

Motivation
Long non-coding RNAs (lncRNAs) are defined as transcripts longer than 200 nt that do not get translated into proteins. Often these transcripts are processed (spliced, capped and polyadenylated) and some are known to have important biological functions. However, most lncRNAs have unknown or poorly understood functions. Nevertheless, because of their potential role in cancer, lncRNAs are receiving a lot of attention, and the need for computational tools to predict their possible mechanisms of action is more than ever. Fundamentally, most of the known lncRNA mechanisms involve RNA–RNA and/or RNA–protein interactions. Through accurate predictions of each kind of interaction and integration of these predictions, it is possible to elucidate potential mechanisms for a given lncRNA.

Results
Here, we introduce MechRNA, a pipeline for corroborating RNA–RNA interaction prediction and protein binding prediction for identifying possible lncRNA mechanisms involving specific targets or on a transcriptome-wide scale. The first stage uses a version of IntaRNA2 with added functionality for efficient prediction of RNA–RNA interactions with very long input sequences, allowing for large-scale analysis of lncRNA interactions with little or no loss of optimality. The second stage integrates protein binding information pre-computed by GraphProt, for both the lncRNA and the target. The final stage involves inferring the most likely mechanism for each lncRNA/target pair. This is achieved by generating candidate mechanisms from the predicted interactions, the relative locations of these interactions and correlation data, followed by selection of the most likely mechanistic explanation using a combined P-value. We applied MechRNA on a number of recently identified cancer-related lncRNAs (PCAT1, PCAT29 and ARLnc1) and also on two well-studied lncRNAs (PCA3 and 7SL). This led to the identification of hundreds of high confidence potential targets for each lncRNA and corresponding mechanisms. These predictions include the known competitive mechanism of 7SL with HuR for binding on the tumor suppressor TP53, as well as mechanisms expanding what is known about PCAT1 and ARLn1 and their targets BRCA2 and AR, respectively. For PCAT1-BRCA2, the mechanism involves competitive binding with HuR, which we confirmed using HuR immunoprecipitation assays.

Availability and implementation
MechRNA is available for download at https://bitbucket.org/compbio/mechrna.

Supplementary information
Supplementary data are available at Bioinformatics online.
Shadows of a Closed Curve
Authors: Dobbins Michael Gene , Kim Heuna , Montejano Luis , Roldán-Pensado Edgardo 
Published: March 2018

Abstract
A shadow of a geometric object A in a given direction v is the orthogonal projection of A on the hyperplane orthogonal to v. We show that any topological embedding of a circle into Euclidean d-space can have at most two shadows that are simple paths in linearly independent directions. The proof is topological and uses an analog of basic properties of degree of maps on a circle to relations on a circle. This extends a previous result that dealt with the case d = 3.
Sustained Lesion and Shedding Rate Reductions in Genital Herpes Patients 24 Months after Immunization with GEN-003, a Genital Herpes Immunotherapy
Authors: Heineman Thomas , Mcneil Lisa K , Oliphant Thomas , Natenshon Andrew , Van Wagoner Nicholas , Flechtner Jessica B , Hetherington Seth ,   GEN-003-002b Investigators
Published: March 2018

Abstract

Background
Herpes simplex viruses (HSVs) are the main cause of genital ulcers worldwide. GEN-003 is an investigational genital herpes immunotherapy composed of HSV-2 antigens gD2DTMR and ICP4.2, and the saponin-based adjuvant Matrix-M2TM (MM2). In a Phase 2 dose-ranging study (GEN-003-002), 3 doses of GEN-003 reduced HSV-2 lesion rate (percent of days with genital lesions) and anogenital HSV-2 shedding rate (percent of days with detectable virus). The antiviral effect of GEN-003 persisted to 12 months after the 3-dose vaccination regimen. We report here the results of an extension study to evaluate efficacy and immunogenicity of GEN-003 at 24 months post-vaccination.

Methods
GEN-003-002 subjects who received at least 1 dose of GEN-003 (dose groups: 30 or 60 µg of antigens combined with 25, 50 or 75 µg of MM2) were eligible to enroll in the extension study. At 24 months post-vaccination, anogenital swabs were collected twice daily for 28 days for HSV-2 DNA detection by quantitative PCR. During this period, subjects also reported genital herpes lesion data via a daily reporting tool. Blood samples were collected at the end of the swab collection period to evaluate humoral and cellular immune responses. HSV-2 immunoglobulin G (IgG) was measured by ELISA, and HSV-2 neutralizing antibodies were measured by a colorimetric assay. Cellular responses were evaluated in peripheral blood mononuclear cells using an interferon-g/granzyme B Fluorospot assay.

Results
140 subjects were enrolled. At 24 months, those in the two best-performing GEN-003-002 study groups, 60 µg antigens combined with either 50 or 75 µg MM2 (60/50 and 60/75, respectively), recorded decreased mean viral shedding rates of 58% and 69% below baseline, similar to the 12-month shedding rate reductions, and mean anogenital lesion rates of 77% and 39% below baseline, respectively (Fig 1). In all dose groups, mean IgG titers to ICP4.2 and gD2ΔTMR were sustained from 12 to 24 months. Similarly, mean neutralizing antibody titers did not change significantly from month 12 to 24.

Conclusion
GEN-003 induces reductions in HSV-2 shedding and genital herpes lesion rates that persist to 24 months following treatment. Humoral immune responses to GEN-003 are maintained at 24 months after immunization.

Disclosures
T. Heineman, Genocea Biosciences: Employee, Salary. L. K. Mcneil, Genocea Biosciences: Employee, Salary. T. Oliphant, Genocea Biosciences: Consultant, Consulting fee. A. Natenshon, Genocea Biosciences: Employee, Salary. N. Van Wagoner, Genocea Biosciences: Consultant, Research support and Travel support to present at scientific meetings .J. B. Flechtner, Genocea Biosciences: Employee, Salary S. Hetherington, Genocea Biosciences: Employee, Salary/
Minimum Acceptable Susceptibility of Empirical Antibiotic Regimens for Gram-Negative Bloodstream Infections
Authors: Haggard Emily , Hagedorn Maureen , Bookstaver P. Brandon , Justo Julie Ann , Kohn Joseph , Al-Hasan Majdi N. 
Published: March 2018

Background
There is a paucity of data describing the minimum acceptable susceptibility (MAS) of empirical antimicrobial regimens based on severity of illness, prognosis, and practitioner level of comfort.

Objective
The purpose of this study was to determine the MAS used by pharmacists involved in antimicrobial decision making for gram-negative bloodstream infections.

Methods
This cross-sectional survey targeted infectious diseases and/or critical care pharmacists. The 11-item survey was distributed electronically in September and October 2014. Survey respondents were asked to indicate a 2-digit number (between 59% and 99%) representing their MAS targets for each clinical scenario (3 cases of gram-negative bloodstream infection of varying complexity and prognosis and 1 control scenario of uncomplicated cystitis). The median MAS were reported by prognosis as estimated by the Bloodstream Infection Mortality Risk Score (BSIMRS) and respondent characteristics.

Results
Among 316 participant pharmacists, 209 (66%) and 52 (17%) identified infectious diseases and critical care as specialty practice areas, respectively. The median MAS was 90% for both case 1 (poor prognosis; BSIMRS: 13) and case 2 (guarded prognosis; BSIMRS: 8), 85% for case 3 (good prognosis; BSIMRS: 2), and 80% for case 4 (uncomplicated cystitis; BSIMRS: 0). There was a significant increase in median MAS as BSIMRS increased from 0 to 2 (P < 0.001) and from 2 to 8 (P < 0.001). The median MAS plateaued as BSIMRS increased from 8 to 13 (P = 0.20).

Conclusion
There was a proportional increase in respondents' median MAS as severity and complexity of infections progressed until MAS reached the maximum in patients with guarded/poor prognosis.
Chronic Q Fever Infection Mimicking Hematological Malignancy
Authors: Khateeb Jasmin , Stern Anat , Yaseen Hiba , Levi Yishai , Khamaisi Mogher 
Published: March 2018

Abstract
Chronic Q fever (QF) infection is considered a synonym for endocarditis and, less frequently, hepatitis. Rarely, it may resemble hematological malignancies. We present an unusual chronic QF infection mimicking lymphoma with secondary hemophagocytosis. A high level of suspicion for QF is essential in cases with an unusual course.
Gait Variability and Energy Cost of Oveground Walking in Persons With Multiple Sclerosis
Authors: Sebastião Emerson , Bollaert Rachel E. , Hubbard Elizabeth A. , Motl Robert W. 
Published: March 2018

Objective
This study examined the associations between gait variability based on common spatiotemporal parameters and energetic cost of walking in persons with multiple sclerosis.

Design
Eighty-six persons with multiple sclerosis underwent the 6-min walk while wearing a portable metabolic unit. The cost of walking was generated by dividing the net steady-state VO2 (milliliter per kilogram per minute) by walking speed during the 6-min walk. Participants further completed two trials of walking on the GAITRite mat at a self-selected pace for measuring spatiotemporal parameters. Variability of step length, step time, stride length, swing time, stance time, stride velocity, and single- and double-support time was indexed by the coefficient of variation.

Results
Variability in the spatiotemporal variables and Expanded Disability Status Scale scores were significantly correlated with cost of walking (i.e., ρ = 0.25–0.36). Multivariate analysis revealed that disability (Expanded Disability Status Scale: β = 0.186), stance time variability (β = 1.446), and step length variability (β = −1.216) explained significant variance (R
2 = 0.38, P < 0.001) in cost of walking.

Conclusions
We provide evidence of the positive association between gait variability and cost of walking during overground walking in persons with multiple sclerosis. The findings highlight the need for interventions aiming to reduce gait variability, thereby reducing the energetic demands of walking in this population.
Interhomolog polymorphism shapes meiotic crossover withinRAC1andRPP13disease resistance genes
Authors: Serra Heïdi , Choi Kyuha , Zhao Xiaohui , Blackwell Alexander R. , Henderson Ian R. 
Published: March 2018

AbstractDuring meiosis chromosomes undergo DNA double-strand breaks (DSBs), which can produce crossovers via interhomolog repair. Meiotic recombination frequency is variable along chromosomes and concentrates in narrow hotspots. We mapped crossovers withinArabidopsis thalianahotspots located within theRAC1andRPP13disease resistance genes, using varying haplotypic combinations. We observed a negative non-linear relationship between interhomolog divergence and crossover frequency, consistent with polymorphism suppressing crossover repair of DSBs. Anti-recombinase mutantsfancm,recq4a recq4b,figl1andmsh2, or lines with increasedHEI10dosage, are known to show increased crossovers. Surprisingly,RAC1crossovers were either unchanged or decreased in these genetic backgrounds. We employed deep-sequencing of crossovers to examine recombination topology withinRAC1, in wild type,fancmandrecq4a recq4bmutant backgrounds. TheRAC1recombination landscape was broadly conserved in anti-recombinase mutants and showed a negative relationship with interhomolog divergence. However, crossovers at theRAC15’-end were relatively suppressed inrecq4a recq4bbackgrounds, indicating that local context influences recombination outcomes. Our results demonstrate the importance of interhomolog divergence in shaping recombination within plant disease resistance genes and crossover hotspots.
Cohort-based smoothing methods for age-specific contact rates
Authors: Vandendijck Yannick , Gressani Oswaldo , Faes Christel , Camarda Carlo G. , Hens Niel 
Published: March 2018

AbstractThe use of social contact rates is widespread in infectious disease modeling since it has been shown that they are key driving forces of important epidemiological parameters. Quantification of contact patterns is crucial to parametrize dynamic transmission models and to provide insights on the (basic) reproduction number. Information on social interactions, can (for instance) be obtained from population-based contact surveys, such as the European Commission project POLYMOD. Estimation of age-specific contact rates from these studies is often done using a piecewise constant approach or bivariate smoothing techniques. For the latter, typically, smoothing is done in the dimensions of the respondent’s and contact’s age. We propose a new flexible strategy based on a smoothing constrained approach - taking into account the reciprocal nature of contacts - where the contact rates are assumed smooth from a cohort perspective as well as from the age distribution of contacts. This is achieved by smoothing over the diagonal components (including all subdiagonals) of the social contact matrix. This approach is supported by the fact that people age with time and thus motivates smoothly varying contact rates from a cohort angle. Two approaches that allow for smoothing of social contact data over cohorts are proposed namely, (1) reordering of the diagonal components of the social contact matrix; and (2) reordering of the penalty matrix associated with the diagonal components. Parameter estimation is done in the likelihood framework by using constrained penalized iterative reweighted least squares (C-PIRLS), under Poisson and negative Binomial distributional assumptions for the observed contacts. A simulation study underlines the benefits of cohort-based smoothing based on two scalar measures of performance. Finally, the proposed methods are illustrated on the Belgian POLYMOD data of 2006. Code to reproduce the results of the article can be downloaded on this Github repositoryhttps://github.com/oswaldogressani/Cohort_smoothing.
Computation is concentrated in rich clubs of local cortical neurons
Authors: Faber Samantha P. , Timme Nicholas M. , Beggs John M. , Newman Ehren L. 
Published: March 2018

ABSTRACTTo understand how neural circuits process information, it is essential to identify the relationship between computation and circuit topology. Rich-clubs, highly interconnected sets of neurons, are known to propagate a disproportionate amount of information within cortical circuits. Here, we test the hypothesis that rich-clubs also perform a disproportionate amount of computation. To do so, we recorded the spiking activity of on average ∼300 well-isolated individual neurons from organotypic cortical cultures. We then constructed weighted, directed networks reflecting the effective connectivity between the neurons. For each neuron, we quantified the amount of computation it performed based on its inputs. We found that rich-club neurons compute ∼200% more information than neurons outside of the rich club. Indeed, the amount of computation performed in the rich-club was proportional to the amount information propagation by the same neurons. This suggests that, in these circuits, information propagation drives computation. Comparing the computation-to-propagation ratio inside versus outside of the rich club showed that rich clubs compute at a slightly, though significantly, reduced level (∼4% lower). In total, our findings indicate that rich club topology in effective cortical circuits supports not only information propagation but also neural computation.AUTHOR SUMMARYHere we answer the question of whether rich club topology in functional cortical circuits supports neural computation as it has been previously shown to do for information propagation. To do so, we combined network analysis with information theoretic tools to analyze the spiking activity of hundreds of neurons recorded from organotypic cultures of mouse somatosensory cortex. We found that neurons in rich clubs computed significantly more than neurons outside of rich clubs, suggesting that rich-clubs do support computation in cortical circuits. Indeed, the amount of computation that we found in the rich club was proportional to the amount of information they propagate suggesting that, in these circuits, information propagation drives computation.
Dynamic asset allocation with asymmetric jump distribution
Authors: Li Xiaoping , Zhou Chunyang 
Published: March 2018

Purpose
The purpose of this paper is to solve the optimal dynamic portfolio problem under the double-exponential jump diffusion (DEJD) distribution, which can allow the asset returns to jump asymmetrically.

Design/methodology/approach
The authors solve the problem by solving the HJB equation. Meanwhile, in the presence of jump component in the asset returns, the investor may suffer a large loss due to high leveraged position, so the authors impose the short-sale and borrowing constraints when solving the optimization problem.

Findings
The authors provide sufficient conditions such that the optimal solution exists and show theoretically that the optimal risky asset weight is an increasing function of jump-up probability and average jump-up size and a decreasing function of average jump-down size.

Research limitations/implications
In this study, the authors assume that the jump-up and jump-down intensities are constant. In the future, the authors will relax the assumption and allows the jump intensities to be time varying.

Practical implications
Empirical studies based on Chinese Shanghai stock index data show that the jump distribution of Shanghai index returns is asymmetric, and the DEJD model can fit the data better than the log-normal jump-diffusion model. The numerical results are consistent with the theoretical prediction, and the authors find that the less risk-averse investor will suffer more economic cost if ignoring asymmetric jump distribution.

Originality/value
This study first examines how asymmetric jumps affect the investor’s portfolio allocation.
Organizational barriers to employee training and learning: evidence from the automotive sector
Authors: Anlesinya Alex 
Published: March 2018

Purpose
This study examines the factors that hinder employee training and learning in the automotive industry in Ghana, Africa.

Design/methodology/approach
The study adopts quantitative research methodology and cross-sectional survey design. Eighty-nine usable questionnaires from employees of an automotive organization in Ghana are used. Descriptive statistics and one-sample t-test are used for the analyses.

Findings
The results indicate that organizational culture, poor management commitment to training, inadequate promotion prospects, and lack of transparency and fairness in trainees’ selection are the most common barriers to employee training and learning.

Practical implications
Top management should provide opportunities to employees to apply new skills and knowledge they acquired. Fair and transparent procedures should be used to select training beneficiaries. Finally, organizations should develop cultural systems that encourage continuous learning motivation among their employees.

Originality/value
In this era of knowledge-driven economy, this research highlights factors that inhibit employees’ motivation to learn.
The governance of spectrum: a possible venue of accountability for global telecommunication
Authors: Rozgonyi Krisztina 
Published: March 2018

PurposeThe paper aims to explore accountability as a virtue and as a mechanism (Bovens, 2010) of global telecommunication operators in the process of governing spectrum and of broadband development. The two concepts of accountability are juxtaposed with operators’ corporate reporting practices and spectrum licensing procedures of European national regulatory authorities (NRAs) and are analysed accordingly. The paper argues that spectrum licensing within the European Union regulatory context offers possible venues for policy intervention, rendering telecom providers to take an account on their global operations. Corruption is the case study to draw connections to public accountability, with a focus on the information and communication technology global market activity.Design/methodology/approachSpectrum bidding processes of European NRAs were analysed according to published documentation of auctions and to answers of NRAs on specific aspects of their licensing practices. Auctioning cases on 800 MHz band frequencies (790-862 MHz, or the “digital dividend”) were selected in countries where telecoms involved in corruption cases were based or where corrupt practices were revealed. Furthermore, a survey was carried out between 08 March and 03 June 2017 – coordinated by the Radio Spectrum Policy Group among its 28 members – on inquiring about licensing practices of NRAs during spectrum trading with respect to identifying beneficial ownership of bidders to spectrum.FindingsFindings show that European NRAs are in possession of regulatory tools that could enforce telecoms’ public accountability; there are strong arguments on the need for European and national-level policy interventions. Spectrum licensing procedures are offering possible and potential venues of accountability. Further legislative action is necessary to adopt a minimum set of criteria applicable in the licensing process. Harmonised implementation by NRAs should further develop new standards fostering transparency.Originality/valueInformation about the ethical behaviour and corruption of European telecom operators is surprisingly scarce and unsystematic, particularly considering the centrality of those actors in advancing a number of the aims of the historical Millennium Development Goals and the new Sustainable Development Goals of the United Nations. Research into the governance of spectrum as a possible venue of accountability, and the findings shed new light on regulatory aspects of telecommunication in a global perspective.