bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-resolved compound repositioning predictions on a text-mined knowledge network
Authors: Mayers Michael , Shu Li Tong , Queralt-Rosinach Núria , Su Andrew I 
Published: May 2019

AbstractBackgroundComputational compound repositioning has the potential for identifying new uses for existing drugs, and new algorithms and data source aggregation strategies provide ever-improving results via in silico metrics. However, even with these advances, the number of compounds successfully repositioned via computational screening remains low. New strategies for algorithm evaluation that more accurately reflect the repositioning potential of a compound could provide a better target for future optimizations.ResultsUsing a text-mined database, we applied a previously described network-based computational repositioning algorithm, yielding strong results via cross-validation, averaging 0.95 AUROC on test-set indications. The text-mined data was then used to build networks corresponding to different time-points in biomedical knowledge. Training the algorithm on contemporary indications and testing on future showed a marked reduction in performance, peaking in performance metrics with the 1985 network at an AUROC of .797. Examining performance reductions due to removal of specific types of relationships highlighted the importance of drug-drug and disease-disease similarity metrics. Using data from future timepoints, we demonstrate that further acquisition of these kinds of data may help improve computational results.ConclusionsEvaluating a repositioning algorithm using indications unknown to input network better tunes its ability to find emerging drug indications, rather than finding those which have been withheld. Focusing efforts on improving algorithmic performance in a time-resolved paradigm may further improve computational repositioning predictions.
From single nuclei to whole genome assemblies
Authors: Montoliu-Nerin Merce , Sánchez-García Marisol , Bergin Claudia , Grabherr Manfred , Ellis Barbara , Kutschera Verena Esther , Kierczak Marcin , Johannesson Hanna , Rosling Anna 
Published: May 2019

SummaryA large proportion of Earth's biodiversity constitutes organisms that cannot be cultured, have cryptic life-cycles and/or live submerged within their substrates1–4. Genomic data are key to unravel both their identity and function5. The development of metagenomic methods6,7 and the advent of single cell sequencing8–10 have revolutionized the study of life and function of cryptic organisms by upending the need for large and pure biological material, and allowing generation of genomic data from complex or limited environmental samples. Genome assemblies from metagenomic data have so far been restricted to organisms with small genomes, such as bacteria11, archaea12 and certain eukaryotes13. On the other hand, single cell technologies have allowed the targeting of unicellular organisms, attaining a better resolution than metagenomics8,9,14–16, moreover, it has allowed the genomic study of cells from complex organisms one cell at a time17,18. However, single cell genomics are not easily applied to multicellular organisms formed by consortia of diverse taxa, and the generation of specific workflows for sequencing and data analysis is needed to expand genomic research to the entire tree of life, including sponges19, lichens3,20, intracellular parasites21,22, and plant endophytes23,24. Among the most important plant endophytes are the obligate mutualistic symbionts, arbuscular mycorrhizal (AM) fungi, that pose an additional challenge with their multinucleate coenocytic mycelia25. Here, the development of a novel single nuclei sequencing and assembly workflow is reported. This workflow allows, for the first time, the generation of reference genome assemblies from large scale, unbiased sorted, and sequenced AM fungal nuclei circumventing tedious, and often impossible, culturing efforts. This method opens infinite possibilities for studies of evolution and adaptation in these important plant symbionts and demonstrates that reference genomes can be generated from complex non-model organisms by isolating only a handful of their nuclei.
Pseudomonas syringaeIncreases Water Availability in Leaf Microenvironments via Production of Hygroscopic Syringafactin
Authors: Hernandez Monica N. , Lindow Steven E. 
Published: May 2019

ABSTRACTThe epiphytic bacteriumPseudomonas syringaestrain B728a produces the biosurfactant syringafactin which is hygroscopic. The water absorbing potential of syringafactin is high. At high relative humidities, syringafactin attracts 250% of its weight in water but is less hygroscopic at lower relative humidities. This suggests that syringafactin’s benefit to the producing cells is strongly context-dependent. The contribution of syringafactin to the water availability around cells on different matrices was assessed by examining water availability biosensor strains that expressgfpvia the water-stress activatedproUpromoter. Wild-type cells exhibited significantly less GFP fluorescence than a syringafactin-deficient strain, on humid but dry filters as well as on leaf surfaces indicating higher water availability. When infiltrated into the leaf apoplast, wild-type cells also subsequently exhibited less GFP fluorescence than a syringafactin-deficient strain. These results suggest that the apoplast is a dry, but humid environment and that, just as on dry but humid leaf surfaces, syringafactin increases liquid water availability and reduces the water stress experienced byP. syringae.IMPORTANCEMany microorganisms, including the plant pathogenPseudomonas syringae, produce amphiphilic compounds known as biosurfactants. While biosurfactants are known to disperse hydrophobic compounds and reduce water tension, they have other properties that can benefit the cells that produce them. Leaf colonizing bacteria experience frequent water stress since liquid water is only transiently present on or in leaf sites that they colonize. The demonstration that syringafactin, a biosurfactant produced byP. syringae, is sufficiently hygroscopic to increase water availability to cells, thus relieving water stress, reveals thatP. syringaecan modify its local habitat both on leaf surfaces and in the leaf apoplast. Such habitat modification may be a common role for biosurfactants produced by other bacterial species that colonize habitats that are not always water saturated such as soil.
A Novel Chromatin-Opening Element for Stable Long-term Transgene Expression
Authors: Rudina Shireen S. , Smolke Christina D. 
Published: May 2019

ABSTRACTLong-term stable expression of transgenes in mammalian cells is a challenge in gene therapy, recombinant protein production, and mammalian synthetic biology due to epigenetic silencing and position effect variegation. While multiple classes of regulatory elements have been discovered and proposed to help stabilize expression, the most efficacious has been the Ubiquitous Chromatin Opening Element (UCOE), and in particular, the prototypical A2UCOE from the HNRPA2B1-CBX3 locus. We developed a feature-driven bioinformatics algorithm to discover other putative UCOEs from the human genome, and identified a novel UCOE (SRF-UCOE) that can resist transgene silencing in the methylation-prone P19 cell line. We demonstrate that a 767 bp core sequence of SRF-UCOE is modular to four common mammalian promoters. Notably, SRF-UCOE stabilizes gene expression in transduced P19 cells up to 2.4-fold better over 26 days than the existing A2UCOE by resisting constructs’ susceptibility to DNA methylation and histone deacetylation. Unlike existing UCOEs, SRF-UCOE lacks inherent transcriptional initiation activity, which can bolster its safe and predictable use in gene therapy constructs. We expect that expanding the set of UCOEs available will expand their utility to novel applications in gene therapy, synthetic biology, and biomanufacturing, as well as contribute to understanding their molecular mechanism.
Energy landscapes reveal agonist control of GPCR activation via microswitches
Authors: Fleetwood Oliver , Matricon Pierre , Carlsson Jens , Delemotte Lucie 
Published: May 2019

AbstractAgonist binding to G protein-coupled receptors (GPCRs) leads to conformational changes in the transmembrane region that activate cytosolic signaling pathways. Al-though high resolution structures of different receptor states are available, atomistic details of the allosteric signalling across the membrane remain elusive. We calculated free energy landscapes of theβ2adrenergic receptors activation using atomistic molecular dynamics simulations in an optimized string of swarms framework, which sheds new light on how microswitches govern the equilibrium between conformational states. Contraction of the extracellular binding site in the presence of the agonist BI-167107 is obligatorily coupled to conformational changes in a connector motif located in the core of the transmembrane region. The connector is probabilistically coupled to the conformation of the intracellular region. An active connector promotes desolvation of a buried cavity, a twist of the conserved NPxxY motif, and an interaction between two conserved tyrosines in transmembrane helices 5 and 7 (Y-Y motif), which leads to a larger population of active-like states at the G protein binding site. This coupling is augmented by protonation of the strongly conserved Asp792.50. The agonist binding site hence communicates with the intracellular region via a cascade of locally connected microswitches. Characterization of these can be used to understand how ligands stabilize distinct receptor states and contribute to development drugs with specific signaling properties. The developed simulation protocol is likely transferable to other class A GPCRs.Graphical TOC Entry
No association of mitochondrial DNA levels in trophectodermal cells with the developmental competence of the blastocyst and pregnancy outcomes
Authors: Ritu G , Veerasigamani Geetha , Ashraf Mohammed C. , Singh Sankalp , Laheri Saniya , Modi Deepak 
Published: May 2019

AbstractStudy questionCan mitochondrial DNA (mtDNA) levels in trophectodermal cells of the blastocyst predict the blastocyst quality, ploidy status, implantation rate and clinical outcomes?Summary answermtDNA levels in trophectodermal cells of the blastocyst do not associate with the blastocyst quality, ploidy status, implantation potential and clinical outcomes, but can differentiate between aneuploid and euploid blastocysts.What we already knowmtDNA levels in the trophectodermal cells have been suggested to be associated with blastocyst morphology, ploidy and implantation rates, and has been proposed as biomarker to access blastocyst quality and predict clinical outcomes. However, discrepancies exist if mtDNA levels could serve as a marker for the same.Study design and durationRetrospective analysis of mtDNA levels in trophectodermal cells obtained from blastocysts undergoing preimplantation genetic testing for aneuploidy (PGT-A) at Craft Hospital & Research Center, Kerala from January 2016-July 2017.Participants/materials and methodsStudy included data from 287 blastocyst from (61) couples who underwent PGT-A using next generation sequencing (NGS). Levels of mtDNA in trophectodermal cells of the blastocyst were estimated by the NGS. Comparison of mtDNA levels with maternal age, blastocyst morphology, ploidy status, implantation rates, miscarriage rates and live birth rate was done.Main resultsThe levels of mtDNA in the trophectoderm of the blastocyst did not correlate with maternal age. There was no significant difference in the mtDNA levels between grade 1 and grade 2 blastocyst. Euploid blastocyst had significantly lower amounts of mtDNA levels in trophectodermal cells of the blastocyst were compared to aneuploid blastocyst. No significant differences were seen between mtDNA levels and implanting and non-implanting blastocysts or those resulted into miscarriage or live birth.LimitationsThe study is limited by a small sample size and hence type II error cannot be ruled out.Wider ImplicationsThe study does not support the potential use of mtDNA levels in the trophectodermal cells as biomarker for blastocyst quality and predicting clinical outcomes needs.Study funding/competing interest(s)There is no external funding for the study. There is no conflict of interest.
Auxin-Induced Actin Cytoskeleton Rearrangements Require AUX1
Authors: Arieti Ruthie S. , Staiger Christopher J. 
Published: May 2019

ABSTRACTThe actin cytoskeleton is required for cell expansion and is implicated in cellular responses to the plant growth hormone auxin. However, the molecular and cellular mechanisms that coordinate auxin signaling, cytoskeletal remodeling, and cell expansion are poorly understood. Previous studies have examined actin cytoskeleton responses to long-term auxin treatment, but plants respond to auxin over short timeframes, and growth changes within minutes of exposure to the hormone. To correlate actin arrays with degree of cell expansion, we used quantitative imaging tools to establish a baseline of actin organization, as well as of individual filament behaviors in root epidermal cells under control conditions and after treatment with a known inhibitor of root growth, the auxin indole-3-acetic acid (IAA). We found that cell length was highly predictive of actin array in control roots, and that short-term IAA treatment stimulated denser, more longitudinal, and more parallel arrays by inducing filament unbundling within minutes. By demonstrating that actin filaments were more “organized” after a treatment that stopped elongation, we show there is no direct relationship between actin organization and cell expansion and refute the hypothesis that “more organized” actin universally correlates with more rapidly growing root cells. The plasma membrane-bound auxin transporter AUXIN RESISTANT 1 (AUX1) has previously been shown necessary for archetypal short-term root growth inhibition in the presence of IAA. Although AUX1 was not previously suspected of being upstream of cytoskeletal responses to IAA, we usedaux1mutants to demonstrate that AUX1 is necessary for the full complement of actin rearrangements in response to auxin, and that cytoplasmic auxin in the form of NAA is sufficient to stimulate a partial actin response. Together, these results are the first to quantitate actin cytoskeleton response to short-term auxin treatments and demonstrate that AUX1 is necessary for short-term actin remodeling.One sentence summaryThe Arabidopsis AUX1 auxin transport protein is necessary for actin cytoskeleton reorganization in response to phytohormone treatment.
Assembly error propagation modeling and coordination error chain construction for aircraft
Authors: Guo Feiyan , Zou Fang , Liu Jian Hua , Xiao Qingdong , Wang Zhongqi 
Published: May 2019

Purpose
Manufacturing errors, which will propagate along the assembly process, are inevitable and difficult to analyze for complex products, such as aircraft. To realize the goal of precise assembly for an aircraft, with revealing the nonlinear transfer mechanism of assembly error, a set of analytical methods with response to the assembly error propagation process are developed. The purpose of this study is to solve the error problems by modeling and constructing the coordination dimension chain to control the consistency of accumulated assembly errors for different assemblies.

Design/methodology/approach
First, with the modeling of basic error sources, mutual interaction relationship of matting error and deformation error is analyzed, and influence matrix is formed. Second, by defining coordination datum transformation process, practical establishing error of assembly coordinate system is studied, and the position of assembly features is modified with actual relocation error considering datum changing. Third, considering the progressive assembly process, error propagation for a single assembly station and multi assembly stations is precisely modeled to gain coordination error chain for different assemblies, and the final coordination error is optimized by controlling the direction and value of accumulated error range.

Findings
Based on the proposed methodology, coordination error chain, which has a direct influence on the property of stealthy and reliability for modern aircrafts, is successfully constructed for the assembly work of the jointing between leading edge flap component and wing component at different assembly stations.

Originality/value
Precise assembly work at different assembly stations is completed to verify methodology’s feasibility. With analyzing the main comprised error items and some optimized solutions, benefit results for the practical engineering application showing that the maximum value of the practical flush of the profiles between the two components is only 0.681 mm, the minimum value is only 0.021 mm, and the average flush of the entire wing component is 0.358 mm, which are in accordance with theoretical calculation results and can successfully fit the assembly requirement. The potential user can be the engineers for manufacturing the complex products.
Modeling of assembly systems with complex structures for throughput analysis during transients
Authors: Hou Yukan , Li Yuan , Ge Yuntian , Zhang Jie , Jiang Shoushan 
Published: May 2019

Purpose
The purpose of this paper is to present an analytical method for throughput analysis of assembly systems with complex structures during transients.

Design/methodology/approach
Among the existing studies on the performance evaluation of assembly systems, most focus on the system performance in steady state. Inspired by the transient analysis of serial production lines, the state transition matrix is derived considering the characteristics of merging structure in assembly systems. The system behavior during transients is described by an ergodic Markov chain, with the states being the occupancy of all buffers. The dynamic model for the throughput analysis is solved using the fixed-point theory.

Findings
This method can be used to predict and evaluate the throughput performance of assembly systems in both transient and steady state. By comparing the model calculation results with the simulation results, this method is proved to be accurate.

Originality/value
This proposed modeling method can depict the throughput performance of assembly systems in both transient and steady state, whereas most exiting methods can be used for only steady-state analysis. In addition, this method shows the potential for the analysis of complex structured assembly systems owing to the low computational complexity.
Evidence based practice among healthcare providers: a cross-sectional study
Authors: Kalavani Khalil , Mohebbifar Rafat , Rafiei Sima 
Published: May 2019

Purpose
Nowadays health systems in most of the countries are trying to build their healthcare provision system based on scientific knowledge based evidence. Evidence-based practice (EBP) is a crucial factor for quality improvement focusing on compliance with clinical standards. The purpose of this paper is to assess evidence-based knowledge and skills among healthcare providers in Qazvin hospitals in 2016.

Design/methodology/approach
This was a descriptive study conducted among 300 health professionals working in hospitals affiliated by Qazvin University of Medical Sciences in 2016. A self-administered questionnaire was used to gather data on health providers’ attitude, knowledge and skill regarding EBP. Descriptive statistics and multiple linear regressions were used to analyze data using SPSS 16 software.

Findings
A total of 254 participants (84.6 percent) completed the questionnaire in which their attitude, knowledge and skill toward EBP were assessed at a low level. Study results indicated that among different occupational groups, physicians and those with greater awareness toward EBP terminology had a more positive attitude compared with others. Furthermore, a higher level of knowledge and skill toward EBP was associated with being a physician and having a positive attitude toward the issue.

Practical implications
Given the importance of EBP and due to insufficient knowledge of healthcare providers about the issue, it is necessary to hold appropriate educational courses to empower health workforce in implementing EBP principles.

Originality/value
The authors applied a self-administered questionnaire to assess health workforce knowledge and skills toward EBP. The results obtaining from the analysis not only highlights weaknesses related to service providers’ knowledge and capabilities to implement EBP but also reveals facilities required for realization of the subject in hospital settings.
Social norm-based gamification to promote eco-friendly food choice
Authors: Berger Verena 
Published: May 2019

Purpose
Digital applications and thus new digital intervention possibilities such as gamification have made their way into our everyday lives. This paper aims to examine to what extent social norm information (SNI) in a game element feedback may increase eco-friendly food choices.

Design/methodology/approach
The effect of social norm-based feedback (SNBF), provided by a “GreenMeter”, was investigated experimentally. The SNI was integrated into the feedback by comparing the subject’s GreenMeter rating with either an injunctive, descriptive or combined SNI.

Findings
Injunctive SNBF was found to be effective in encouraging people to make an eco-friendly food purchasing decision. Combining injunctive with descriptive SNBF or simply providing descriptive SNBF was also found to be better than no intervention at all.

Research limitations/implications
To take further advantage of social norms to make gamification more effective, additional studies are needed in which long-term effects on behavior are investigated, as well as other game elements and target groups are taken into account.

Practical implications
Many people want to choose food that is more eco-friendly but often struggle because of deeply ingrained habits or strong social influences. Consequently, their intentions do not translate into changes in their behavior. Alternative motivational, gamification approaches, like SNBF, may be considered when designing Web-based applications.

Originality/value
The study provides insights into the effectiveness of SNI going beyond text-based interventions. Considering SNI in a specific design of gamification (“GreenMeter”) provided insights into how they could be integrated into dynamic, digital, behavioral change techniques to increase eco-friendly food choices.
Factors affecting the Islamic purchasing behavior – a qualitative study
Authors: Karoui Sedki , Khemakhem Romdhane 
Published: May 2019

PurposeThis study aims to better understand the Islamic consumption incentives because the spectacular flourishing of the halal market in different places around the world has grown the interest in understanding and deciphering the mechanisms behind its development.Design/methodology/approachThrough an exploratory study of some Tunisia-based Islamic groups’ purchasing behavior, this paper investigates factors leading to the purchasing ofhalalgoods (Islamic consumption).FindingsFindings show that the Islamic consumer is more of an Islamist than simply a Muslim. In addition, findings show thathalalconsumption is not merely related to religious affiliations but also the product of numerous cultural, social and psychological factors.Originality/valueIn addition to Islamism and Islamic activism, this paper puts in evidence the role of some post-structural factors such as identity, nostalgia and hedonism in relation to the buying intention ofhalalproducts and services.