bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexually transmitted hepatitis C infection: the evolving epidemic in HIV-positive and HIV-negative MSM
Authors: Lockart Ian , Matthews Gail V. , Danta Mark 
Published: December 2018

Purpose of review
The scale-up of direct-acting antiviral (DAA) therapy and introduction of preexposure prophylaxis (PrEP) has changed the epidemiology of sexually acquired hepatitis C virus (HCV) amongst HIV-positive and HIV-negative MSM.

Recent findings
Sexually acquired HCV continues to occur predominantly amongst HIV-positive MSM. Despite an increased uptake of DAA therapy the incidence of acute HCV has not declined consistently amongst HIV-positive MSM, likely a result of high infection and reinfection rates. Increasing cases of sexually acquired HCV have been reported amongst HIV-negative MSM accessing PrEP. Despite a lower prevalence of HCV at baseline, HIV-negative MSM accessing PrEP have an equally high overall incidence of HCV compared with HIV-positive MSM during follow-up. Behavioural factors (high-risk sexual behaviours and sexualized drug use) appear to be driving this HCV epidemic amongst MSM and effective behavioural interventions and early identification of reinfections are essential to control the HCV epidemic amongst MSM.

Summary
An improved understanding of the epidemiology of sexually acquired HCV will allow implementation of more effective public health interventions to control the transmission of HCV amongst HIV-positive and HIV-negative MSM.
First-of-a-kind muography for nuclear waste characterization
Authors: Mahon David , Clarkson Anthony , Gardner Simon , Ireland David , Jebali Ramsey , Kaiser Ralf , Ryan Matthew , Shearer Craig , Yang Guangliang 
Published: December 2018

In the last decade, there has been a surge in the number of academic research groups and commercial companies exploiting naturally occurring cosmic-ray muons for imaging purposes in a range of industrial and geological applications. Since 2009, researchers at the University of Glasgow and the UK National Nuclear Laboratory (NNL) have pioneered this technique for the characterization of shielded nuclear waste containers with significant investment from the UK Nuclear Decommissioning Authority and Sellafield Ltd. Lynkeos Technology Ltd. was formed in 2016 to commercialize the Muon Imaging System (MIS) technology that resulted from this industry-funded academic research. The design, construction and performance of the Lynkeos MIS is presented along with first experimental and commercial results. The high-resolution images include the identification of small fragments of uranium within a surrogate 500-litre intermediate level waste container and metal inclusions within thermally treated GeoMelt® R&D Product Samples. The latter of these are from Lynkeos' first commercial contract with the UK National Nuclear Laboratory. The Lynkeos MIS will be deployed at the NNL Central Laboratory facility on the Sellafield site in Summer 2018 where it will embark upon a series of industry trials.
This article is part of the Theo Murphy meeting issue ‘Cosmic-ray muography’.
Muography: overview and future directions
Authors: Kaiser Ralf 
Published: December 2018

Cosmic-ray muography uses high-energy particles for imaging applications that are produced by cosmic rays in particle showers in the Earth's atmosphere. This technology has developed rapidly over the last 15 years, and it is currently branching out into many different applications and moving from academic research to commercial application. As in any new sub-field of research and technology, the nomenclature of the field itself is still developing and has not settled yet as new aspects of the field are appearing and with them the terms to describe them. This overview of the field of muography is not going to focus on the physics, on the reconstruction algorithms or on the involved detector technology. Detailed papers on these aspects are included in this issue of Philosophical Transactions A and I will refer to them. Instead, I will give an overview of the field as it is now, in 2018, and try to give an idea of the future directions in this field as I see them.
This article is part of the Theo Murphy meeting issue ‘Cosmic-ray muography’.
Non-destructive testing of industrial equipment using muon radiography
Authors: Arbol Pablo Martinez Ruiz-del , Garcia Pablo Gomez , Gonzalez Carlos Diez , OrioAlonso Aitor 
Published: December 2018

A new application of muon radiography (MR) is presented in the context of non-destructive testing of industrial equipment. The long-term operation of industrial facilities frequently involves the deterioration of critical components such as pipes and cauldrons due to corrosion and other processes. The precise determination of the inner state of this equipment is needed to ensure the integrity of the facility. MR can be used to infer the thickness of these components through the comparison and further classification of muon observables with respect to well-known templates. A simulation example is presented where the thickness of a pipe made of steel is studied using the Point of Closest Approach method and simple Kolmogorov–Smirnov statistical tests. A precision of about 2–4 mm is obtained using a simple detector with a spatial resolution of 4 mm and exposure times of about 2 h.
This article is part of the Theo Murphy meeting issue ‘Cosmic-ray muography’.
INFN muon tomography demonstrator: past and recent results with an eye to near-future activities
Authors: Checchia P. , Benettoni M. , Bettella G. , Conti E. , Cossutta L. , Furlan M. , Gonella F. , Klinger J. , Montecassiano F. , Nebbia G. , Pegoraro M. , Pesente S. , Rigoni Garola A. , Urbani M. , Viesti G. , Vanini S. , Zumerle G. 
Published: December 2018

A short description of the muon tomography demonstrator at the INFN Laboratori Nazionali di Legnaro near Padua, Italy, is given and the principal achievements owing to the data collected at that experimental facility are presented. In particular, the feasibility studies for several applications based on the muon-tomographic technology, within national and European projects, are discussed. The experimental problems and the procedures used to improve the performance are underlined. In addition, new activities and the related detector optimization are illustrated.
This article is part of the Theo Murphy meeting issue ‘Cosmic-ray muography’.
Lingacom muography
Authors: Harel A. , Yaish D. 
Published: December 2018

Lingacom Ltd develops detectors for muography—imaging using cosmic-ray muons—together with imaging algorithms and tools. We present selected simulation results from muon imaging of cargo conta- iners, from a joint muon and X-ray imaging algorithm, and for ground surveys using borehole detectors.
This article is part of the Theo Murphy meeting issue ‘Cosmic-ray muography’.
Japanese volcanoes visualized with muography
Authors: Tanaka Hiroyuki K. M. 
Published: December 2018

High-energy muons that are generated via the reaction between primary cosmic rays and the Earth's atmosphere can be used to map out the density distribution in shallow parts of a volcano's interior. This new subterranean imaging technique called muography has been applied to three different kinds of volcano dynamics in Japan: lava dome formation, vulcanian explosions and magma convection. Taking all of the observational data together, it appears that muography can serve as a new and alternative volcano observation technique, providing a fresh approach to understanding eruption mechanism. This review describes observational studies in which muography has been used to explore the volcano's interior.
This article is part of the Theo Murphy meeting issue ‘Cosmic-ray muography’.
Cancer V-ATPase Expression Signatures: A Distinctive Balance of SubunitCIsoforms in Esophageal Carcinoma
Authors: do Couto Vieira Carvalho dos Santos Juliana , Neto Pedro Nicolau , Costa Evenilton Pessoa , Figueira Frederico Firme , de Almeida Simão Tatiana , Façanha Anna Lvovna Okorokova , Pinto Luis Felipe Ribeiro , Façanha Arnoldo Rocha 
Published: December 2018

ABSTRACTV-ATPases are hetero-oligomeric enzymes consisting of 14 subunits and playing key roles in ion homeostasis and signaling. Differential expressions of these proton pumps have been implicated in carcinogenesis and metastasis. To elucidate putative molecular signatures underlying these phenomena, we evaluated the V-ATPase genes expression in Esophageal Squamous Cell Carcinoma (ESCC) using gene expression microarray data and extended the analysis to other cancers the Oncomine database. Among all differentially expressed genes, those encoding the V-ATPase C isoforms exhibited striking expression patterns validated by qRT-PCR in paired ESCC samples and respective normal surrounding tissues. Structural modeling of C2a isoform uncovered motifs for oncogenic kinases in an additional peptide stretch, and an actin-biding domain downstream to this sequence. This study reveals multi-cancer molecular signatures in the V-ATPase structure and establishes that the expression ratios of its subunits/isoforms could form a conformational code that controls the pump regulation and interactions related to tumorigenic events.
Exact distribution of divergence times from fossil ages and tree topologies
Authors: Didier Gilles , Laurin Michel 
Published: December 2018

AbstractBeing given a phylogenetic tree of both extant and extinct taxa in which the fossil ages are the only temporal information (namely, in which divergence times are considered unknown), we provide a method to compute the exact probability distribution of any divergence time of the tree with regard to any speciation (cladogenesis), extinction and fossilization rates under the Fossilized-Birth-Death model.We use this new method to obtain a probability distribution for the age of Amniota (the synapsid/sauropsid or bird/mammal divergence), one of the most-frequently used dating constraints. Our results suggest an older age (between about 322 and 340 Ma) than has been assumed by most studies that have used this constraint (which typically assumed a best estimate around 310-315 Ma) and provide, for the first time, a method to compute the shape of the probability density for this divergence time.
Cosolvent Effects on the Growth of Protein Aggregates Formed by a Single Domain Globular Protein and an Intrinsically Disordered Protein
Authors: Mondal Balaka , Reddy Govardhan 
Published: December 2018

AbstractCosolvents modulate the stability of protein conformations and exhibit contrasting effects on the kinetics of aggregation by globular proteins and intrinsically disordered proteins (IDPs). The growth of ordered protein aggregates, after the initial nucleation step is believed to proceed through a dock-lock mechanism. We have studied the effect of two denaturants (guanidinium chloride (GdmCl) and urea) and four protective osmolytes (trimethylamine N-oxide (TMAO), sucrose, sarcosine, and sorbitol) on the free energy surface (FES) of the dock-lock growth step of protein aggregation using a coarse-grained protein model and metadynamics simulations. We have used the proteins cSrc-SH3 andAβ9−40as model systems representing globular proteins and IDPs, respectively. The effect of cosolvents on protein conformations is taken into account using the molecular transfer model (MTM). The computed FES shows that protective osmolytes stabilize the compact aggregates, while denaturants destabilize them for both cSrc-SH3 andAβ9−40. However, protective osmolytes increase the effective energy barrier for the multi-step domain swapped dimerization of cSrc-SH3, which is critical to the growth of protein aggregates by globular proteins, thus slowing down overall aggregation rate. Contrastingly, denaturants decrease the effective barrier height for cSrc-SH3 dimerization, and hence enhances the aggregation rate in globular proteins. The simulations further show that cSrc-SH3 monomers unfold before dimerization and the barrier to monomer unfolding regulates the effective rate of agrgegation. In the case of IDP,Aβ9−40, protective osmolytes decrease and denaturants increase the effective barriers in the dock-lock mechanism of fibril growth, leading to faster and slower growth kinetics, respectively.
Rapid Proteomic Screen of CRISPR Experiment Outcome by Data Independent Acquisition Mass Spectrometry: A Case Study for HMGN1
Authors: Mehnert Martin , Li Wenxue , Wu Chongde , Salovska Barbora , Liu Yansheng 
Published: December 2018

AbstractCRISPR-Cas gene editing holds substantial promise in many biomedical disciplines and basic research. Due to the important functional implications of non-histone chromosomal protein HMG-14 (HMGN1) in regulating chromatin structure and tumor immunity, we performed gene knockout of HMGN1 by CRISPR in cancer cells and studied the following proteomic regulation events. In particular, we utilized DIA mass spectrometry (DIA-MS) and reproducibly measured more than 6200 proteins (protein-FDR 1%) and more than 82,000 peptide precursors in the single MS shots of two hours. HMGN1 protein deletion was confidently verified by DIA-MS in all of the clone- and dish- replicates following CRISPR. Statistical analysis revealed 147 proteins changed their expressions significantly after HMGN1 knockout. Functional annotation and enrichment analysis indicate the deletion of HMGN1 induces the histone inactivation, various stress pathways, remodeling of extracellular proteomes, cell proliferation, as well as immune regulation processes such as complement and coagulation cascade and interferon alpha/ gamma response in cancer cells. These results shed new lights on the cellular functions of HMGN1. We suggest that DIA-MS can be reliably used as a rapid, robust, and cost-effective proteomic screening tool to assess the outcome of the CRISPR experiments.
Anatomical diversification of a skeletal novelty in bat feet
Authors: Stanchak Kathryn E. , Arbour Jessica H. , Santana Sharlene E. 
Published: December 2018

ABSTRACTNeomorphic, membrane-associated skeletal rods are found in disparate vertebrate lineages, but their evolution is poorly understood. Here we show that one of these elements—the calcar of bats (Chiroptera)—is a skeletal novelty that has anatomically diversified. Our comparisons of evolutionary models of calcar length and corresponding disparity-through-time analyses indicate that the calcar diversified early in the evolutionary history of Chiroptera, as bats systematically radiated after evolving the capacity for flight. We find interspecific variation in a variety of anatomical parameters of probable importance for calcar function, which suggests that adaptive advantages provided by the calcar led to its anatomical diversification. In addition to overall length, we find that the calcar varies among bats in its tissue composition, and a synovial joint is present at the articulation between the calcar and the calcaneus ankle bone in some species. This suggests the calcar has a kinematic functional role. Our results demonstrate that novel skeletal additions can become integrated into vertebrate body plans and subsequently evolve into a variety of forms, potentially impacting clade diversification by expanding the available morphological space into which organisms can evolve.
Longitudinally persistent cerebrospinal fluid B-cells resist treatment in multiple sclerosis
Authors: Greenfield Ariele L. , Dandekar Ravi , Ramesh Akshaya , Eggers Erica L. , Wu Hao , Laurent Sarah , Harkin William , Pierson Natalie S. , Weber Martin S. , Henry Roland G. , Bischof Antje , Cree Bruce A.C. , Hauser Stephen L. , Wilson Michael R. , von Büdingen H.-Christian 
Published: December 2018

AbstractB-cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related B-cells exist in the cerebrospinal fluid (CSF), meninges, and central nervous system (CNS) parenchyma of MS patients. Longitudinally stable CSF oligoclonal band (OCB) antibody patterns suggest some local CNS B-cell persistence; however, the longitudinal B-cell dynamics within and between the CSF and blood remain unknown. We sought to address this by performing immunoglobulin heavy chain variable region repertoire sequencing on B-cells from longitudinally collected blood and CSF samples of MS patients (n=10). All patients were untreated at the time of the initial sampling; the majority (n=7) were treated with immune modulating therapies 1.2 (+/−0.3 SD) years later during the second sampling. We found clonal persistence of B-cells in the CSF of five patients; these B-cells were frequently immunoglobulin (Ig) class-switched and CD27+. We identified specific blood B-cell subsets that appear to provide input into CNS repertoires over time. We demonstrate complex patterns of clonal B-cell persistence in CSF and blood, even in patients on high-efficacy immune modulating therapy. Our findings support the concept that peripheral B-cell activation and CNS-compartmentalized immune mechanisms are in part therapy-resistant.
A novel NO-dependent ‘molecular-memory-switch’ mediates presynapticexpressionand postsynapticmaintenanceof LTP in the octopus brain
Authors: Turchetti-Maia Ana Luiza , Stern-Mentch Naama , Bidel Flavie , Nesher Nir , Shomrat Tal , Hochner Binyamin 
Published: December 2018

AbstractThe octopus brain shows a robust hippocampal-like activity-dependent LTP, which is NMDA-independent, yet associative and presynaptically expressed and, as shown here, also independent of protein synthesis. Have the molecular mechanisms for mediating this LTP evolved independently or have they converged? Here we report on a distinctive adaptation of the nitric-oxide (NO) system for mediation of the octopus LTP. Unlike the suggested role of NO in LTPinductionin the hippocampus, in octopus, inhibitors of NO-synthase (NOS) did not block LTPinductionbut either 1) reversibly ‘erased’ LTP expression, suggesting that a constitutive elevation in NO mediates the presynaptic LTPexpressionor 2) ‘reversed’ LTPinductionandmaintenancebecause a second LTP could be induced after inhibitor washout. We therefore propose a protein synthesis-independent ‘molecular-switch’, whereby NO-dependent NOS reactivation maintains NOS in its active state. Thus, while the octopus LTP shows marked evolutionary convergence with LTP in vertebrates, an extreme molecular novelty has evolved to mediate it.
Identification of spatially variable genes with graph cuts
Authors: Zhang Ke , Feng Wanwan , Wang Peng 
Published: December 2018

AbstractSingle-cell gene expression data with positional information are critical to dissect mechanisms and architectures of multicellular organisms, but the potential is limited by current data analysis strategies. Here, we present scGCO (single-cell graph cuts optimization), a method based on fast optimization of Markov Random Fields with graph cuts, to identify spatially viable genes. Extensive benchmarking demonstrated that scGCO delivers superior performance with optimal segmentation of spatial patterns, and can process millions of cells in a timely manner owing to its linear scalability.
simuG: a general-purpose genome simulator
Authors: Yue Jia-Xing , Liti Gianni 
Published: December 2018

AbstractSummarySimulated genomes with pre-defined and random genomic variants can be very useful for benchmarking genomic and bioinformatics analyses. Here we introduce simuG, a light-weighted tool for simulating the full-spectrum of genomic variants. The simplicity and versatility of simuG makes it a unique general purpose genome simulator for a wide-range of simulation-based applications.Availability and implementationCode in Perl along with user manual and testing data is available at https://github.com/yjx1217/simuG. This software is free for use under the MIT license.
Genetically distinct clinical subsets, and associations with asthma and eosinophil abundance, within Eosinophilic Granulomatosis with Polyangiitis
Authors: Lyons Paul A , Peters James E , Alberici Federico , Liley James , Coulson Richard M.R. , Astle William , Baldini Chiara , Bonatti Francesco , Cid Maria C , Elding Heather , Emmi Giacomo , Epplen Jörg , Guillevin Loic , Jayne David R. W. , Jiang Tao , Gunnarsson Iva , Lamprecht Peter , Leslie Stephen , Little Mark A. , Martorana Davide , Moosig Frank , Neumann Thomas , Ohlsson Sophie , Quickert Stefanie , Ramirez Giuseppe A. , Rewerska Barbara , Schett Georg , Sinico Renato A. , Szczeklik Wojciech , Tesar Vladimir , Vukcevic Damjan ,   The European Vasculitis Genetics Consortium, Terrier Benjamin , Watts Richard A , Vaglio Augusto , Holle Julia U , Wallace Chris , Smith Kenneth G. C. 
Published: December 2018

AbstractEosinophilic granulomatosis with polyangiitis (EGPA: formerly Churg-Strauss syndrome) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasm antibodies (ANCA) specific for myeloperoxidase (MPO). We performed a genome-wide association study (GWAS) of EGPA, testing 7.5 million genetic variants in 684 cases and 6,838 controls. Case-control analyses were performed for EGPA as a whole, and stratified by ANCA. To increase power, we used a conditional false discovery rate method to leverage findings from GWASs of related phenotypes. In total, 11 variants were associated with EGPA, two specifically with ANCA-negative EGPA, and one (HLA-DQ) with MPO+ANCA EGPA. Many variants were associated with asthma, eosinophilic and immune-mediated diseases and, strikingly, nine were associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia underlies EGPA susceptibility. We demonstrate that EGPA comprises two genetically and clinically distinct syndromes, with ANCA-negative EGPA genetically more similar to asthma. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an MHC association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Five identified candidate genes are targets of therapies in development, supporting their exploration in EGPA.
Pan-Cancer and Single-Cell modelling of genomic alterations through gene expression
Authors: Mercatelli Daniele , Ray Forest , Giorgi Federico M. 
Published: December 2018

AbstractCancer is a disease often characterized by the presence of multiple genomic alterations, which trigger altered transcriptional patterns and gene expression, which in turn sustain the processes of tumorigenesis, tumor progression and tumor maintenance. The links between genomic alterations and gene expression profiles can be utilized as the basis to build specific molecular tumorigenic relationships. In this study we perform pan-cancer predictions of the presence of single somatic mutations and copy number variations using machine learning approaches on gene expression profiles. We show that gene expression can be used to predict genomic alterations in every tumor type, where some alterations are more predictable than others. We propose gene aggregation as a tool to improve the accuracy of alteration prediction models from gene expression profiles. Ultimately, we show how this principle can be beneficial in intrinsically noisy datasets, such as those based on single cell sequencing.Author SummaryIn this article we show that transcript abundance can be used to predict the presence or absence of the majority of genomic alterations present in human cancer. We also show how these predictions can be improved by aggregating genes into small networks to counteract the effects of transcript measurement noise.