bluuebunny/crossref_metadata_2025 huggingface dataset:
Channel aware reputation system with adaptive detection using AODV protocol during forward attack in wireless sensor network
Authors: Sakthi Prabha R
Published: November 2019

Wireless sensing element networks (WSNs) area unit vulnerable to selective forwarding attacks which will maliciously drop asubset of forwarding packets to degrade network performance and jeopardize the data integrity. Meanwhile, due to the unstable wireless channel in WSNs, the packet loss rate during the communication of sensing element nodes could also be high and vary from time to time. It poses a good challenge to tell apart the malicious drop and traditional packet loss. During this paper, we propose a Channel-aware name System with adaptive detection threshold (CRS-A) to find selective forwarding attacks in WSNs. The CRS-A evaluates the information forwarding behaviors of sensor nodes, in step with the deviation of the monitored packet loss and also the calculable traditional loss. To optimize the detection accuracy of CRS-A, we tend to in theory derive the best threshold for forwarding analysis, that is adaptive to the time varied channel condition and also the calculable attack chances of compromised nodes. What is more, AN attack-tolerant information forwarding theme is developed to collaborate with CRS-A for stimulating the forwarding cooperation of compromised nodes and up the information delivery magnitude relation of the network. Extensive simulation results demonstrate that CRS-A will accurately find selective forwarding attacks and determine the compromised sensing element nodes, whereas the attack-tolerant information forwarding theme will significantly improve the information delivery magnitude relation of the network.
Multilinking of Professional Analog Wireless Communication Networks
Authors: Joshi Vivekanand K , Sampath Sivaperumal
Published: November 2019

The paper explains design of Professional Analog Wireless Communication System. The designing of basic analog wireless communication network, its components, their parameters and communication quality deciding factors are discussed. For expanding a wireless system, multilinking of wireless networks is essential. Major problem encountered during interconnections of such networks is time delay occurred due to propagation of electromagnetic waves through air. This paper suggests one method to eliminate the problem. It has been successfully implemented in one of the big cities in Maharashtra State.
Modelling and simulation of electric power steering system using permanent magnet synchronous motor
Authors: Hiremath Rahul R , Isha T B
Published: November 2019

This paper presents a control technique for Electric Power Steering System (EPS) using Permanent Magnet Synchronous motor (PMSM) for steering application. The EPS model is developed using the mathematical equations; mechanical subsystem of steering unit is modelled using the dynamic equations of steering unit. The objective of EPS system is to provide the assist torque to the steering wheel to drive the vehicle, here PMSM provides the additional assist torque along with the driver input to steer the vehicle. The control logic implemented here considers the input torque from steering wheel and vehicle speed. Depending upon these two inputs, the q-axis current component required for the PMSM motor to provide the additional assist torque is computed. The complete EPS system is modelled in Matlab/Simulink and simulated for different driving inputs.
Effect of pH Solutions on Using Waste Marble powder to Enhance Mortar Compressive Strength
Authors: Jafar Meerza Al Jaaf Hyman , Abed Al-wahab Ali Manolia , Salih Al-Jadiri Rand
Published: November 2019

The aim of this study is to improve the compressive strength of mortar by adding a recycled material (marble powder) at different weights gradually to the mortar. The samples were prepared and treated with different pH solutions to investigate how can effect compressive strength. The results showed that after preparing the sample of mortar by adding different weights of marble powder, the Compressive strength of the sample of (4 gm) weight of marble powder had the highest value comparing with other samples. The compressive strength for the samples were treated with different pH showed that it decreased with increasing acidity (pH from 1 to 6), but the other sample’s compressive strength increased with increasing alkalinity (pH from 8 to 14). At (pH from 1 to 14), the compressive strength was increasing gradually.
Microstructure evolution and coercivity enhancment of sintered Nd–Fe–B magnets by grain boundary diffusion with Cu aided TbF3
Authors: Gao Xi , Li Jun , Zhao Wei , Liu Ying , Wang Renquan , Liao Lele
Published: November 2019

Compared with the TbF3 grain boundary diffusion (GBD) magnet, in this study, Cu aided TbF3 GBD was applied to Nd-Fe-B magnets to further improve the coercivity. It is found that the coercivity increased sharply from 17.42 kOe to 25.43 kOe when the diffusion source is the mix powders of Cu and TbF3, higher than 21.25 kOe with single TbF3 as the diffusion source. The wettability of the grain boundary phases were improved owing to the accumulation of Cu in grain boundary. The grains were uniformly enveloped by grain boundary phase with the help of Cu addition. The microstructure analysis indicated that the diffusion depth of Tb increased significantly due to the modified grain boundaries which offered better tunnels for the diffusion of Tb.
Grain refining in weld metal using short-pulsed laser ablation during CW laser welding of 2024-T3 aluminum alloy
Authors: Kasuga Masaki , Sano Tomokazu , Hirose Akio
Published: November 2019

The 2024 aluminum alloy is used extensively in the aircraft and aerospace industries because of its excellent mechanical properties. However, the weldability of 2024 aluminum alloy is generally low because it contains a high number of solutes, such as copper (Cu), magnesium (Mg), and manganese (Mn), causing solidification cracking. If high speed welding of 2024 aluminum alloy without the use of filler is achieved, the applicability of 2024 aluminum alloys will expand. Grain refining is one of the methods used to prevent solidification cracking in weld metal, although it has never been achieved for high-speed laser welding of 2024 aluminum alloy without filler. Here, we propose a short-pulsed, laser-induced, grain-refining method during continuous wave laser welding without filler. Bead-on-plate welding was performed on a 2024-T3 aluminum alloy at a welding speed of 1 m min−1 with a single mode fiber laser at a wavelength of 1070 nm and power of 1 kW. Areas in and around the molten pool were irradiated with nanosecond laser pulses at a wavelength of 1064 nm, pulse width of 10 ns, and pulse energy of 430 mJ. The grain-refinement effect was confirmed when laser pulses were irradiated on the molten pool. The grain-refinement region was formed in a semicircular shape along the solid–liquid interface. Results of the vertical section indicate that the grain-refinement region reached a depth of 1 mm along the solid–liquid interface. The Vickers hardness test results demonstrated that the hardness increased as a result of grain refinement and that the progress of solidification cracking was suppressed in the grain refinement region.
On the inconsistent treatment of gene-protein-reaction rules in context-specific metabolic models
Authors: Ponce-de-León Miguel , Apaolaza Iñigo , Valencia Alfonso , Planes Francisco J
Published: November 2019

Supplementary information:  Supplementary data are available at Bioinformatics online.
Differentiating isoform functions with collaborative matrix factorization
Authors: Wang Keyao , Wang Jun , Domeniconi Carlotta , Zhang Xiangliang , Yu Guoxian
Published: November 2019

Motivation

Isoforms are alternatively spliced mRNAs of genes. They can be translated into different functional proteoforms, and thus greatly increase the functional diversity of protein variants (or proteoforms). Differentiating the functions of isoforms (or proteoforms) helps understanding the underlying pathology of various complex diseases at a deeper granularity. Since existing functional genomic databases uniformly record the annotations at the gene-level, and rarely record the annotations at the isoform-level, differentiating isoform functions is more challenging than the traditional gene-level function prediction.

Results

Several approaches have been proposed to differentiate the functions of isoforms. They generally follow the multi-instance learning paradigm by viewing each gene as a bag and the spliced isoforms as its instances, and push functions of bags onto instances. These approaches implicitly assume the collected annotations of genes are complete and only integrate multiple RNA-seq datasets. As such, they have compromised performance. We propose a data integrative solution (called DisoFun) to Differentiate isoform Functions with collaborative matrix factorization. DisoFun assumes the functional annotations of genes are aggregated from those of key isoforms. It collaboratively factorizes the isoform data matrix and gene-term data matrix (storing Gene Ontology annotations of genes) into low-rank matrices to simultaneously explore the latent key isoforms, and achieve function prediction by aggregating predictions to their originating genes. In addition, it leverages the PPI network and Gene Ontology structure to further coordinate the matrix factorization. Extensive experimental results show that DisoFun improves the area under the receiver operating characteristic curve and area under the precision-recall curve of existing solutions by at least 7.7 and 28.9%, respectively. We further investigate DisoFun on four exemplar genes (LMNA, ADAM15, BCL2L1 and CFLAR) with known functions at the isoform-level, and observed that DisoFun can differentiate functions of their isoforms with 90.5% accuracy.

Availability and implementation

The code of DisoFun is available at mlda.swu.edu.cn/codes.php?name=DisoFun.

Supplementary information

Supplementary data are available at Bioinformatics online.
Somatic selection distinguishes oncogenes and tumor suppressor genes
Authors: Chandrashekar Pramod , Ahmadinejad Navid , Wang Junwen , Sekulic Aleksandar , Egan Jan B , Asmann Yan W , Kumar Sudhir , Maley Carlo , Liu Li
Published: November 2019

Motivation

Functions of cancer driver genes vary substantially across tissues and organs. Distinguishing passenger genes, oncogenes (OGs) and tumor-suppressor genes (TSGs) for each cancer type is critical for understanding tumor biology and identifying clinically actionable targets. Although many computational tools are available to predict putative cancer driver genes, resources for context-aware classifications of OGs and TSGs are limited.

Results

We show that the direction and magnitude of somatic selection of protein-coding mutations are significantly different for passenger genes, OGs and TSGs. Based on these patterns, we develop a new method (genes under selection in tumors) to discover OGs and TSGs in a cancer-type specific manner. Genes under selection in tumors shows a high accuracy (92%) when evaluated via strict cross-validations. Its application to 10 172 tumor exomes found known and novel cancer drivers with high tissue-specificities. In 11 out of 13 OGs shared among multiple cancer types, we found functional domains selectively engaged in different cancers, suggesting differences in disease mechanisms.

Availability and implementation

An R implementation of the GUST algorithm is available at https://github.com/liliulab/gust. A database with pre-computed results is available at https://liliulab.shinyapps.io/gust.

Supplementary information

Supplementary data are available at Bioinformatics online.
Priors for genotyping polyploids
Authors: Gerard David , Ferrão Luís Felipe Ventorim
Published: November 2019

Motivation

Empirical Bayes techniques to genotype polyploid organisms usually either (i) assume technical artifacts are known a priori or (ii) estimate technical artifacts simultaneously with the prior genotype distribution. Case (i) is unappealing as it places the onus on the researcher to estimate these artifacts, or to ensure that there are no systematic biases in the data. However, as we demonstrate with a few empirical examples, case (ii) makes choosing the class of prior genotype distributions extremely important. Choosing a class is either too flexible or too restrictive results in poor genotyping performance.

Results

We propose two classes of prior genotype distributions that are of intermediate levels of flexibility: the class of proportional normal distributions and the class of unimodal distributions. We provide a complete characterization of and optimization details for the class of unimodal distributions. We demonstrate, using both simulated and real data that using these classes results in superior genotyping performance.

Availability and implementation

Genotyping methods that use these priors are implemented in the updog R package available on the Comprehensive R Archive Network: https://cran.r-project.org/package=updog. All code needed to reproduce the results of this article is available on GitHub: https://github.com/dcgerard/reproduce_prior_sims.

Supplementary information

Supplementary data are available at Bioinformatics online.
Systematics of Vriesea (Bromeliaceae): phylogenetic relationships based on nuclear gene and partial plastome sequences
Authors: Machado Talita Mota , Loiseau Oriane , Paris Margot , Weigand Anna , Versieux Leonardo M , Stehmann João Renato , Lexer Christian , Salamin Nicolas
Published: November 2019

Vriesea is the second largest genus in Tillandsioideae, the most diverse subfamily of Bromeliaceae. Although recent studies focusing on Tillandsioideae have improved the systematics of Vriesea, no consensus has been reached regarding the circumscription of the genus. Here, we present a phylogenetic analysis of core Tillandsioideae using the nuclear gene phyC and plastid data obtained from genome skimming. We investigate evolutionary relationships at the intergeneric level in Vrieseeae and at the intrageneric level in Vriesea s.s. We sampled a comprehensive dataset, including 11 genera of Tillandsioideae and nearly 50% of all known Vriesea spp. Using a genome skimming approach, we obtained a 78 483-bp plastome alignment containing 35 complete and 55 partial protein-coding genes. Phylogenetic trees were reconstructed using maximum-likelihood based on three datasets: (1) the 78 483 bp plastome alignment; (2) the nuclear gene phyC and (3) a concatenated alignment of 18 subselected plastid genes + phyC. Additionally, a Bayesian inference was performed on the second and third datasets. These analyses revealed that Vriesea s.s. forms a well-supported clade encompassing most of the species of the genus. However, our results also identified several remaining issues in the systematics of Vriesea, including a few species nested in Tillandsia and Stigmatodon. Finally, we recognize some putative groups within Vriesea s.s., which we discuss in the light of their morphological and ecological characteristics.
A causal role for TRESK loss of function in migraine mechanisms
Authors: Pettingill Philippa , Weir Greg A , Wei Tina , Wu Yukyee , Flower Grace , Lalic Tatjana , Handel Adam , Duggal Galbha , Chintawar Satyan , Cheung Jonathan , Arunasalam Kanisa , Couper Elizabeth , Haupt Larisa M , Griffiths Lyn R , Bassett Andrew , Cowley Sally A , Cader M Zameel
Published: November 2019

The two-pore potassium channel TRESK is a potential drug target in pain and migraine. Pettingill et al. show that the F139WfsX2 mutation causes TRESK loss of function and hyperexcitability in nociceptors derived from iPSCs of patients with migraine. Cloxyquin, a TRESK activator, reverses migraine-relevant phenotypes in vitro and in vivo.
Bio-AnswerFinder: a system to find answers to questions from biomedical texts
Authors: Ozyurt Ibrahim Burak , Bandrowski Anita , Grethe Jeffrey S
Published: November 2019

The ever accelerating pace of biomedical research results in corresponding acceleration in the volume of biomedical literature created. Since new research builds upon existing knowledge, the rate of increase in the available knowledge encoded in biomedical literature makes the easy access to that implicit knowledge more vital over time. Toward the goal of making implicit knowledge in the biomedical literature easily accessible to biomedical researchers, we introduce a question answering system called Bio-AnswerFinder. Bio-AnswerFinder uses a weighted-relaxed word mover's distance based similarity on word/phrase embeddings learned from PubMed abstracts to rank answers after question focus entity type filtering. Our approach retrieves relevant documents iteratively via enhanced keyword queries from a traditional search engine. To improve document retrieval performance, we introduced a supervised long short term memory neural network to select keywords from the question to facilitate iterative keyword search. Our unsupervised baseline system achieves a mean reciprocal rank score of 0.46 and Precision@1 of 0.32 on 936 questions from BioASQ. The answer sentences are further ranked by a fine-tuned bidirectional encoder representation from transformers (BERT) classifier trained using 100 answer candidate sentences per question for 492 BioASQ questions. To test ranking performance, we report a blind test on 100 questions that three independent annotators scored. These experts preferred BERT based reranking with 7% improvement on MRR and 13% improvement on Precision@1 scores on average.
Using Music to Develop a Multisensory Communicative Environment for People with Late-Stage Dementia
Authors: Clare Amy , Camic Paul M , Crutch Sebastian J , West Julian , Harding Emma , Brotherhood Emilie
Published: November 2019

Background and Objectives

Research has indicated the benefit of music interventions on biological, psychological, and cognitive aspects of dementias, yet there is limited research focusing on music’s role in communication. This study developed a conceptual understanding of how people with late-stage dementia may express themselves nonverbally and interact with others during a live music group over time.

Research Design and Methods

Eight people with advanced dementias in residential care (aged 82–97 years), four care staff, and three musicians participated in 8-hr-long weekly live Music for Life sessions and listened to 1-hr-long recorded music session. Visual grounded theory was used to analyze video data collected nonintrusively via the Fly 360-degree camera.

Results

The live music group facilitated a multisensory communicative environment allowing for verbal and nonverbal communicative actions, social interactional components and agency to develop over time. These aspects were influenced by three factors: time, one-to-one interaction within a group setting and the characteristics of the music.

Discussion and Implications

Nonverbal communication in later-stage dementia may be overlooked or underestimated by busy care staff and families. Using music as an interactive way to communicate can help develop mirroring and turn-taking which has been shown to improve quality of life for people with communication impairment, increase their nonverbal communication and allow for a connection to be built between people. Although further research is recommended, individuals responsible for residential care should feel confident that the development of ongoing music groups for this population is warranted as part of ongoing care.
The master transcription factor SOX2, mutated in anophthalmia/microphthalmia, is post-transcriptionally regulated by the conserved RNA-binding protein RBM24 in vertebrate eye development
Authors: Dash Soma , Brastrom Lindy K , Patel Shaili D , Scott C Anthony , Slusarski Diane C , Lachke Salil A
Published: November 2019

Mutations in the key transcription factor, SOX2, alone account for 20% of anophthalmia (no eye) and microphthalmia (small eye) birth defects in humans—yet its regulation is not well understood, especially on the post-transcription level. We report the unprecedented finding that the conserved RNA-binding motif protein, RBM24, positively controls Sox2 mRNA stability and is necessary for optimal SOX2 mRNA and protein levels in development, perturbation of which causes ocular defects, including microphthalmia and anophthalmia. RNA immunoprecipitation assay indicates that RBM24 protein interacts with Sox2 mRNA in mouse embryonic eye tissue. and electrophoretic mobility shift assay shows that RBM24 directly binds to the Sox2 mRNA 3’UTR, which is dependent on AU-rich elements (ARE) present in the Sox2 mRNA 3’UTR. Further, we demonstrate that Sox2 3’UTR AREs are necessary for RBM24-based elevation of Sox2 mRNA half-life. We find that this novel RBM24–Sox2 regulatory module is essential for early eye development in vertebrates. We show that Rbm24-targeted deletion using a constitutive CMV-driven Cre in mouse, and rbm24a-CRISPR/Cas9-targeted mutation or morpholino knockdown in zebrafish, results in Sox2 downregulation and causes the developmental defects anophthalmia or microphthalmia, similar to human SOX2-deficiency defects. We further show that Rbm24 deficiency leads to apoptotic defects in mouse ocular tissue and downregulation of eye development markers Lhx2, Pax6, Jag1, E-cadherin and gamma-crystallins. These data highlight the exquisite specificity that conserved RNA-binding proteins like RBM24 mediate in the post-transcriptional control of key transcription factors, namely, SOX2, associated with organogenesis and human developmental defects.
A tutorial on sample size calculation for multiple-period cluster randomized parallel, cross-over and stepped-wedge trials using the Shiny CRT Calculator
Authors: Hemming Karla , Kasza Jessica , Hooper Richard , Forbes Andrew , Taljaard Monica
Published: November 2019

It has long been recognized that sample size calculations for cluster randomized trials require consideration of the correlation between multiple observations within the same cluster. When measurements are taken at anything other than a single point in time, these correlations depend not only on the cluster but also on the time separation between measurements and additionally, on whether different participants (cross-sectional designs) or the same participants (cohort designs) are repeatedly measured. This is particularly relevant in trials with multiple periods of measurement, such as the cluster cross-over and stepped-wedge designs, but also to some degree in parallel designs. Several papers describing sample size methodology for these designs have been published, but this methodology might not be accessible to all researchers. In this article we provide a tutorial on sample size calculation for cluster randomized designs with particular emphasis on designs with multiple periods of measurement and provide a web-based tool, the Shiny CRT Calculator, to allow researchers to easily conduct these sample size calculations. We consider both cross-sectional and cohort designs and allow for a variety of assumed within-cluster correlation structures. We consider cluster heterogeneity in treatment effects (for designs where treatment is crossed with cluster), as well as individually randomized group-treatment trials with differential clustering between arms, for example designs where clustering arises from interventions being delivered in groups. The calculator will compute power or precision, as a function of cluster size or number of clusters, for a wide variety of designs and correlation structures. We illustrate the methodology and the flexibility of the Shiny CRT Calculator using a range of examples.
Performance study of a dual-fluid photovoltaic thermal collector with reflection and refraction solar concentrators
Authors: Baljit S S S , Chan H Y , Zaidi S H , Sopian K
Published: November 2019

The temperature of a photovoltaic (PV) plate increases with increasing absorbed irradiation, leading to degradation of the electrical efficiency of the PV cells. The heat can be dissipated by air or water to prevent the deterioration of the cells. In this study, a concentrating photovoltaic thermal (PV-T) dual-fluid solar collector is proposed in which two types of concentrators are integrated. The collector’s performance was analysed with air and water as the working fluids. Analytical expressions were derived from the energy balance equations for each component of the collector. The mean temperature values of the PV plate, air inlet/outlet, water inlet/outlet, glaze and collector back wall were experimentally recorded under different fluid mass flow rates and solar irradiations. The readings were then used to compute the thermal and electrical efficiencies of the collector. The results obtained from the numerical and experimental analyses were compared and evaluated by employing the mean absolute percentage error method. The results show that incorporating two fluids increases the thermal and electrical efficiencies. The total thermal and electrical efficiencies achieved are 67.00% and 13.02%, respectively, at air and water mass flow rates of 0.0103 kg/s and 0.0164 kg/s, respectively, and a solar irradiation of 650 Wm−2. The outcomes of this research are expected to help advance the designs of dual-fluid PV-T solar collectors and offering a broader range of thermal applications.
Embodying the Pain and Cruelty of Others
Authors: Shapiro-Phim Toni
Published: November 2019

A ground-breaking performing arts-centered reparations project of the Extraordinary Chambers in the Courts of Cambodia – also known as the Khmer Rouge Tribunal – is entitled Phka Sla. The Phka Sla initiative was proposed by survivors of the practice of forced marriage under the Khmer Rouge. While organizations collaborating on Phka Sla are assessing the impact of its innovative dance drama, exhibition and other activities on audiences and survivors, this article offers initial observations regarding the impact of embodying survivor testimony on the artists themselves.
The Ethiopia healthcare quality initiative: design and initial lessons learned
Authors: Magge Hema , Kiflie Abiyou , Nimako Kojo , Brooks Kathryn , Sodzi-Tettey Sodzi , Mobisson-Etuk Nneka , Mulissa Zewdie , Bitewulign Befikadu , Abate Mehiret , Biadgo Abera , Alemu Haregweni , Seman Yakob , Kassa Munir , Barker Pierre , Burrsa Daniel Gebremichael
Published: November 2019

Objective

To describe the development, implementation and initial outcomes of a national quality improvement (QI) intervention in Ethiopia.

Design

Retrospective descriptive study of initial prototype phase implementation outcomes.

Setting

All public facilities in one selected prototype district in each of four agrarian regions.

Participants

Facility QI teams composed of managers, healthcare workers and health extension workers.

Interventions

The Ethiopian Federal Ministry of Health (FMoH) and the Institute for Healthcare Improvement co-designed a three-pronged approach to accelerate health system improvement nationally, which included developing a national healthcare quality strategy (NHQS); building QI capability at all health system levels and introducing scalable district MNH QI collaboratives across four regions, involving healthcare providers and managers.

Outcome measures

Implementation outcomes including fidelity, acceptability, adoption and program effectiveness.

Results

The NHQS was launched in 2016 and governance structures were established at the federal, regional and sub-regional levels to oversee implementation. A total of 212 federal, regional and woreda managers have been trained in context-specific QI methods, and a national FMoH-owned in-service curriculum has been developed. Four prototype improvement collaboratives have been completed with high fidelity and acceptability. About 102 MNH change ideas were tested and a change package was developed with 83 successfully tested ideas.

Conclusion

The initial successes observed are attributable to the FMoH’s commitment in implementing the initiative, the active engagement of all stakeholders and the district-wide approach utilized. Challenges included weak data systems and security concerns. The second phase—in 26 district-level collaboratives—is now underway.
An HMM-based synthetic view generator to improve the efficiency of ensemble systems
Authors: Borrajo L , Vieira A Seara , Iglesias E L
Published: November 2019

One of the most active areas of research in semi-supervised learning has been to study methods for constructing good ensembles of classifiers. Ensemble systems are techniques that create multiple models and then combine them to produce improved results. These systems usually produce more accurate solutions than a single model would. Specially, multi-view ensemble systems improve the accuracy of text classification because they optimize the functions to exploit different views of the same input data. However, despite being more promising than the single-view approaches, document datasets often have no natural multiple views available. This study proposes an algorithm to generate a synthetic view from a standard text dataset. The model generates a new view from the standard bag-of-words approach using an algorithm based on hidden Markov models (HMMs). To show the effectiveness of the proposed HMM-based synthetic view generation method, it has been integrated in a co-training ensemble system and tested with four text corpora: Reuters, 20 Newsgroup, TREC Genomics and OHSUMED. The results obtained are promising, showing a significant increase in the efficiency of the ensemble system compared to a single-view approach.
Solid-state formation of CO and H2CO via the CHOCHO + H reaction
Authors: Leroux Killian , Guillemin Jean-Claude , Krim Lahouari
Published: November 2019

Glycolaldehyde (CHOCH2OH) and ethylene glycol (HOCH2CH2OH) are among many complex organic molecules detected in the interstellar medium (ISM). Astrophysical models proposed very often that the formation of these compounds would be directly linked to the hydrogenation of glyoxal (CHOCHO), a potential precursor which is not yet detected in the ISM. We have performed, in this work, surface and bulk hydrogenations of solid CHOCHO under ISM conditions in order to confirm or invalidate the astrophysical modelling of glyoxal transformation. Our results show that the hydrogenation of glyoxal does not lead to the formation of detectable amounts of heavier organic molecules such as glycolaldehyde and ethylene glycol but rather to lighter CO-bearing species such as CO, H2CO, and CO–H2CO, a reaction intermediate resulting from an H-addition–elimination process on CHOCHO and where CO is linked to H2CO. The solid phase formation of such a reaction intermediate has been confirmed through the neon matrix isolation of CO–H2CO species. Additionally, the CHOCHO + H solid-state reaction might also lead to the production of CH3OH formed under our experimental conditions as a secondary product resulting from the hydrogenation of formaldehyde.
Visual Opsin Diversity in Sharks and Rays
Authors: Hart Nathan S , Lamb Trevor D , Patel Hardip R , Chuah Aaron , Natoli Riccardo C , Hudson Nicholas J , Cutmore Scott C , Davies Wayne I L , Collin Shaun P , Hunt David M
Published: November 2019

The diversity of color vision systems found in extant vertebrates suggests that different evolutionary selection pressures have driven specializations in photoreceptor complement and visual pigment spectral tuning appropriate for an animal’s behavior, habitat, and life history. Aquatic vertebrates in particular show high variability in chromatic vision and have become important models for understanding the role of color vision in prey detection, predator avoidance, and social interactions. In this study, we examined the capacity for chromatic vision in elasmobranch fishes, a group that have received relatively little attention to date. We used microspectrophotometry to measure the spectral absorbance of the visual pigments in the outer segments of individual photoreceptors from several ray and shark species, and we sequenced the opsin mRNAs obtained from the retinas of the same species, as well as from additional elasmobranch species. We reveal the phylogenetically widespread occurrence of dichromatic color vision in rays based on two cone opsins, RH2 and LWS. We also confirm that all shark species studied to date appear to be cone monochromats but report that in different species the single cone opsin may be of either the LWS or the RH2 class. From this, we infer that cone monochromacy in sharks has evolved independently on multiple occasions. Together with earlier discoveries in secondarily aquatic marine mammals, this suggests that cone-based color vision may be of little use for large marine predators, such as sharks, pinnipeds, and cetaceans.
Specific enhancer selection by IRF3, IRF5 and IRF9 is determined by ISRE half-sites, 5′ and 3′ flanking bases, collaborating transcription factors and the chromatin environment in a combinatorial fashion
Authors: Csumita Mária , Csermely Attila , Horvath Attila , Nagy Gergely , Monori Fanny , Göczi Loránd , Orbea Hans-Acha , Reith Walter , Széles Lajos
Published: November 2019

IRF3, IRF5 and IRF9 are transcription factors, which play distinct roles in the regulation of antiviral and inflammatory responses. The determinants that mediate IRF-specific enhancer selection are not fully understood. To uncover regions occupied predominantly by IRF3, IRF5 or IRF9, we performed ChIP-seq experiments in activated murine dendritic cells. The identified regions were analysed with respect to the enrichment of DNA motifs, the interferon-stimulated response element (ISRE) and ISRE half-site variants, and chromatin accessibility. Using a machine learning method, we investigated the predictability of IRF-dominance. We found that IRF5-dominant regions differed fundamentally from the IRF3- and IRF9-dominant regions: ISREs were rare, while the NFKB motif and special ISRE half-sites, such as 5′-GAGA-3′ and 5′-GACA-3′, were enriched. IRF3- and IRF9-dominant regions were characterized by the enriched ISRE motif and lower frequency of accessible chromatin. Enrichment analysis and the machine learning method uncovered the features that favour IRF3 or IRF9 dominancy (e.g. a tripartite form of ISRE and motifs for NF-κB for IRF3, and the GAS motif and certain ISRE variants for IRF9). This study contributes to our understanding of how IRF members, which bind overlapping sets of DNA sequences, can initiate signal-dependent responses without activating superfluous or harmful programmes.
An R-loop-initiated CSB–RAD52–POLD3 pathway suppresses ROS-induced telomeric DNA breaks
Authors: Tan Jun , Duan Meihan , Yadav Tribhuwan , Phoon Laiyee , Wang Xiangyu , Zhang Jia-Min , Zou Lee , Lan Li
Published: November 2019

Reactive oxygen species (ROS) inflict multiple types of lesions in DNA, threatening genomic integrity. How cells respond to ROS-induced DNA damage at telomeres is still largely unknown. Here, we show that ROS-induced DNA damage at telomeres triggers R-loop accumulation in a TERRA- and TRF2-dependent manner. Both ROS-induced single- and double-strand DNA breaks (SSBs and DSBs) contribute to R-loop induction, promoting the localization of CSB and RAD52 to damaged telomeres. RAD52 is recruited to telomeric R-loops through its interactions with both CSB and DNA:RNA hybrids. Both CSB and RAD52 are required for the efficient repair of ROS-induced telomeric DSBs. The function of RAD52 in telomere repair is dependent on its ability to bind and recruit POLD3, a protein critical for break-induced DNA replication (BIR). Thus, ROS-induced telomeric R-loops promote repair of telomeric DSBs through CSB–RAD52–POLD3-mediated BIR, a previously unknown pathway protecting telomeres from ROS. ROS-induced telomeric SSBs may not only give rise to DSBs indirectly, but also promote DSB repair by inducing R-loops, revealing an unexpected interplay between distinct ROS-induced DNA lesions.
FIN-Seq: transcriptional profiling of specific cell types from frozen archived tissue of the human central nervous system
Authors: Amamoto Ryoji , Zuccaro Emanuela , Curry Nathan C , Khurana Sonia , Chen Hsu-Hsin , Cepko Constance L , Arlotta Paola
Published: November 2019

Thousands of frozen, archived tissue samples from the human central nervous system (CNS) are currently available in brain banks. As recent developments in RNA sequencing technologies are beginning to elucidate the cellular diversity present within the human CNS, it is becoming clear that an understanding of this diversity would greatly benefit from deeper transcriptional analyses. Single cell and single nucleus RNA profiling provide one avenue to decipher this heterogeneity. An alternative, complementary approach is to profile isolated, pre-defined cell types and use methods that can be applied to many archived human tissue samples that have been stored long-term. Here, we developed FIN-Seq (Frozen Immunolabeled Nuclei Sequencing), a method that accomplishes these goals. FIN-Seq uses immunohistochemical isolation of nuclei of specific cell types from frozen human tissue, followed by bulk RNA-Sequencing. We applied this method to frozen postmortem samples of human cerebral cortex and retina and were able to identify transcripts, including low abundance transcripts, in specific cell types.
Lipids at the plant–animal interface: a stable isotope labelling method to evaluate the assimilation of essential fatty acids in the marine copepod Calanus finmarchicus
Authors: Helenius Laura , Budge Suzanne , Duerksen Steven , Devred Emmanuel , Johnson Catherine L
Published: November 2019

Linking production, transfer and subsequent bioavailability of nutritionally significant matter from phytoplankton to higher trophic levels is a fundamental aspect in understanding marine food webs. The plant–animal interface is of interest because of the highly variable transfer between producers and consumers, and the myriad of factors that influence it. Essential fatty acids (EFAs) are dietary nutrients that are necessary for normal function in all consumers, yet it remains unclear how efficiently they are transferred through marine food webs. We introduced a 13C-labelled carbon source to the cryptophyte Rhodomonas salina to quantify primary production of two omega-3 long-chain polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We investigated transfer and assimilation efficiencies of these EFAs from phytoplankton to the calanoid copepod Calanus finmarchicus in an 8-day feeding experiment. We found low production of both EFAs in R. salina. Assimilation efficiencies of both EFAs ranged from 5 to 15% throughout the experiment, remaining slightly higher on average for DHA. This was mirrored in more efficient trophic transfer of DHA (up to 28%, compared to 13% for EPA). These results add to previously scarce experiments empirically quantifying the assimilation and transfer efficiency of EFAs in a basic marine planktonic food chain.
Eosinophilic granulomatosis with polyangiitis: understanding the disease and its management
Authors: Trivioli Giorgio , Terrier Benjamin , Vaglio Augusto
Published: November 2019

Eosinophilic granulomatosis with polyangiitis is characterized by asthma, blood and tissue eosinophilia and small-vessel vasculitis. The clinical presentation is variable, but two main clinic-pathologic subsets can be distinguished: one hallmarked by positive ANCA and predominant ‘vasculitic’ manifestations (e.g. glomerulonephritis, purpura and mononeuritis multiplex) and the other by negative ANCA and prominent ‘eosinophilic’ manifestations (e.g. lung infiltrates and cardiomyopathy). The pathogenesis is not fully understood but probably results from the interplay between T and B cells and eosinophils. Eosinophilic granulomatosis with polyangiitis must be differentiated from several conditions, including hypereosinophilic syndromes and other small-vessel vasculitides. The overall survival is good; however, patients frequently relapse and have persistent symptoms. The recently developed monoclonal antibodies targeting B cells and eosinophilopoietic cytokines such as IL-5 are emerging as valid alternatives to conventional immunosuppressive therapies. In this review, we discuss the essential features of eosinophilic granulomatosis with polyangiitis, with particular respect to the most relevant issues concerning clinical presentation and management.
High-Throughput Screening to Evaluate Inhibition of Bile Acid Transporters Using Human Hepatocytes Isolated From Chimeric Mice
Authors: Kohara Hiroshi , Bajaj Piyush , Yamanaka Kazunori , Miyawaki Akimitsu , Harada Kosuke , Miyamoto Kazumasa , Matsui Toshikatsu , Okai Yoshiko , Wagoner Matthew , Shinozawa Tadahiro
Published: November 2019

Cholestasis resulting from hepatic bile acid efflux transporter inhibition may contribute to drug-induced liver injury (DILI). This condition is a common safety-related reason for drug attrition and withdrawal. To screen for safety risks associated with efflux transport inhibition, we developed a high-throughput cellular assay for different drug discovery phases. Hepatocytes isolated from chimeric mice with humanized livers presented gene expression resembling that of the human liver and demonstrated apical membrane polarity when sandwiched between Matrigel and collagen. The fluorescent bile acid-derivative cholyl-l-lysyl-fluorescein (CLF) was used to quantify drug-induced efflux transport inhibition in hepatocytes. Cyclosporine inhibited CLF accumulation in the apical bile canalicular lumen in a concentration-dependent manner. The assay had equivalent predictive power to a primary human hepatocyte-based assay and greater predictive power than an assay performed with rat hepatocytes. Predictive power was tested using 45 pharmaceutical compounds, and 91.3% of the compounds with cholestatic potential (21/23) had margins (IC50/Cmax) < 20. In contrast, 90.9% (20/22) of compounds without cholestatic potential had IC50/Cmax>20. Assay sensitivity and specificity were 91.3% and 90.9%, respectively. We suggest that this improved assay performance could result from higher expression of efflux transporters, metabolic pathways, and/or species differences. Given the long-term supply of cells from the same donor, the humanized mouse-derived hepatocyte-based CLF efflux assay could be a valuable tool for predicting cholestatic DILI.
Baseline Sensitivity of Botrytis cinerea Isolates from Strawberry to Isofetamid Compared to other SDHIs
Authors: Zuniga Adrian I. , Oliveira Michelle S. , Rebello Carolina S. , Peres Natalia A.
Published: November 2019

Succinate dehydrogenase inhibitors (SDHIs) are the fungicides most commonly used to control Botrytis fruit rot on commercial strawberry in Florida. The medium-to-high risk of selection of resistance in the causal agent Botrytis cinerea is a threat to the efficacy of this fungicide group. In this study, we characterized the sensitivity of B. cinerea to the SDHI isofetamid, evaluated the SdhB gene mutation associated with resistance, and monitored resistance frequencies to five SDHI fungicides for two consecutive seasons. EC50 values of 70 isolates were obtained using the spiral gradient dilution (SGD) method and averaged 0.098 µg/ml of isofetamid. EC50 averages of 3.04 and >500.00 µg/ml were obtained for isolates with the N230I and P225F mutations indicating moderate and high resistance to isofetamid, respectively. A total of 565 B. cinerea isolates collected during 2015–2016 and 2016–2017 seasons from strawberry nurseries and Florida production fields were evaluated using conidial germination assays. Results for the first season showed resistance frequencies of 95, 33, 21, 25, and 0% to boscalid, penthiopyrad, fluopyram, benzovindiflupyr, and isofetamid, respectively. The respective resistance frequencies for the following season were 91, 95, 44, 27, and 1.3%. Only three isolates were found to be moderately resistant to isofetamid during the second season, and the mutation N230I was identified after sequence analysis. These isolates were confirmed to be resistant to isofetamid in fruit assays with disease incidence of 55.6 to 77.0%; however, the conidial production of the isolates was inhibited by an average of 83.9%. In general, isofetamid efficacy was higher than the other evaluated SDHIs, but a slight increase in resistance frequencies was observed in our study.
Detection of Phenylpropanoids in Citrus Leaves Produced in Response to Xanthomonas citri subsp. citri
Authors: Ference Christopher M. , Manthey John A. , Narciso Jan A. , Jones Jeffrey B. , Baldwin Elizabeth A.
Published: November 2019

Citrus canker (CC), caused by the bacterial pathogen Xanthomonas citri subsp. citri, impacts citrus production in many areas of the world by reducing yields, degrading tree health, and severely blemishing the outer peels of fresh fruit. The relative susceptibility to CC among different species of Citrus varies from the highly susceptible lime (Citrus × aurantifolia), sweet orange (C. × sinensis), and grapefruit (C. × paradisi) to the much less susceptible calamondin (C. × microcarpa) and kumquat (C. japonica). This investigation compares the responses to infection with X. citri subsp. citri of these five genotypes with respect to phenylpropanoid compound profiles and relative increases or decreases of specific compounds postinoculation. In response to X. citri subsp. citri infection, all hosts possessed increased concentrations of phenylpropanoids in leaf tissue, whereas the similarly treated nonhost orange jessamine (Murraya paniculata) did not. Several of the tested genotypes exhibited notably increased production of fluorescent phenylpropanoids, including umbelliferone, herniarin, auraptene, scoparone, and others. The profiles of these compounds and their levels of production varied among the tested species yet all investigated Citrus genotypes exhibited increased concentrations of phenylpropanoids regardless of their degree of susceptibility to X. citri subsp. citri. Kumquat and calamondin, the tested genotypes least susceptible to X. citri subsp. citri, also exhibited the highest levels of the dihydrochalcone 3′,5′-di-C-glucosyl phloretin, the aglycone portion of which, phloretin, is a known antibiotic, although levels of this compound were not affected by inoculation with X. citri subsp. citri.
Effects of Adding Oxycodone to Ropivacaine on Labor Analgesia
Authors: Zhong Heying Y. , Yang Zeyong Y. , Zhang Wangping , Cai Shu
Published: November 2019

Background:

It has been reported that oxycodone is superior to the other opioids for the treatment of visceral pain. During the first stage of labor, pain is mainly caused by uterine contractions (visceral pain). It seems that oxycodone is more suitable for labor analgesia. During this study, we investigated the effects of adding oxycodone to ropivacaine on epidural analgesia during labor.

Materials and Methods:

Eighty nulliparous parturients were randomly divided into 2 groups. Group A received 0.2 mg/mL oxycodone plus 0.1% ropivacaine for epidural analgesia and group C (control group) received 0.1% ropivacaine alone for epidural analgesia. The onset time and duration of analgesia, duration of labor stages, delivery outcome, analgesic effect, Bromage scores, blood pressure, heart rate, and neonatal Apgar scores were recorded. Umbilical arterial blood was collected to analyze. Side effects, if any, were also recorded.

Results:

The visual analog scale of pain was lower at 2 and 4 hours after analgesia and 10 cm cervical dilatation in group A compared with group C (P=0.021, 0.018, and 0.009, respectively). The onset time of analgesia was shorter in group A than that in group C (13.3±2.8 vs. 14.9±3.6 min, P=0.032). There were no significant differences between the 2 groups in terms of the duration of labor stages, delivery outcome, Bromage score, neonatal Apgar score, or umbilical arterial blood pH. The duration of analgesia was significantly longer in group A than in group C (326.2±56.5 vs. 68.4±10.5 min, P=0.000), but the incidence of pruritus was higher in group A than in group C (10% vs. 0%, P=0.115).

Conclusions:

This study demonstrates that epidural oxycodone may accelerate the onset of analgesia and obviously prolong the duration of analgesia during labor without increasing adverse effects associated with the neonate. However, it may cause a higher incidence of maternal pruritus (registration number: ChiCTR1800016483).