bluuebunny/crossref_metadata_2025 huggingface dataset:
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

V-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.
PathoPhenoDB: linking human pathogens to their disease phenotypes in support of infectious disease research
Authors: Kafkas Senay , Abdelhakim Marwa , Hashish Yasmeen , Kulmanov Maxat , Abdellatif Marwa , Schofield Paul N , Hoehndorf Robert
Published: December 2018

Understanding the relationship between the pathophysiology of infectious disease, the biology of the causative agent and the development of therapeutic and diagnostic approaches is dependent on the synthesis of a wide range of types of information. Provision of a comprehensive and integrated disease phenotype knowledgebase has the potential to provide novel and orthogonal sources of information for the understanding of infectious agent pathogenesis, and support for research on disease mechanisms. We have developed PathoPhenoDB, a database containing pathogen-to-phenotype associations. PathoPhenoDB relies on manual curation of pathogen-disease relations, on ontology-based text mining as well as manual curation to associate phenotypes with infectious disease. Using Semantic Web technologies, PathoPhenoDB also links to knowledge about drug resistance mechanisms and drugs used in the treatment of infectious diseases. PathoPhenoDB is accessible at http://patho.phenomebrowser.net/, and the data is freely available through a public SPARQL endpoint.
Exact distribution of divergence times from fossil ages and tree topologies
Authors: Didier Gilles , Laurin Michel
Published: December 2018

Being 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.
Tax4Fun2: a R-based tool for the rapid prediction of habitat-specific functional profiles and functional redundancy based on 16S rRNA gene marker gene sequences
Authors: Wemheuer Franziska , Taylor Jessica A , Daniel Rolf , Johnston Emma , Meinicke Peter , Thomas Torsten , Wemheuer Bernd
Published: December 2018

Assessing the functional capability and redundancy of a microbial community is a major challenge in environmental microbiology. To address this challenge, we developed Tax4Fun2, a R-based tool for the rapid prediction of functional profiles and functional redundancy of prokaryotic communities from 16S rRNA gene sequences. By incorporating user-defined, habitat-specific genomic information, the accuracy and robustness of predicted functional profiles can be substantially enhanced.
Circulating CD4+ memory T cells give rise to a CD69+ resident memory T cell population in non-inflamed human skin
Authors: Klicznik Maria M , Benedetti Ariane , Stoecklinger Angelika , Campbell Daniel J , Gratz Iris K
Published: December 2018

The blood of human adults contains a pool of circulating CD4+ memory T cells and normal human skin contains a CD4+CD69+ memory T cell population that produce IL17 in response to Candida albicans. Here we studied the generation of CD4+CD69+ memory T cells in human skin from a pool of circulating CD4+ memory T cells. Using adoptive transfer of human PBMC into a skin-humanized mouse model we discovered the generation of CD4+CD69+ resident memory T cells in human skin in absence of infection or inflammation. These CD4+CD69+ resident memory T cells were activated and displayed heightened effector function in response to Candida albicans. These studies demonstrate that a CD4+CD69+ T cell population can be established in human skin from a pool of circulating CD4+ memory T cells in absence of infection/inflammation. The described process might be a novel way to spread antigen-specific immunity at large barrier sites even in absence of infection or inflammation.
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

Cosolvents 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

CRISPR-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.
Peer pressure from a Proteus mirabilis self-recognition system controls participation in cooperative swarm motility:
Authors: Tipping Murray J , Gibbs Karine A
Published: December 2018

Colonies of the opportunistic pathogen Proteus mirabilis can distinguish self from non-self: in swarming colonies of two different strains, one strain excludes the other from the expanding colony edge. Predominant models characterize bacterial kin discrimination as immediate antagonism towards non-kin cells, typically through delivery of toxin effector molecules from one cell into its neighbor. Upon effector delivery, receiving cells must either neutralize it by presenting a cognate anti-toxin, as would a clonal sibling, or suffer cell death or irreversible growth inhibition, as would a non-kin cell. Here we expand this paradigm to explain the non-lethal Ids self-recognition system, which stops access to a cooperative social behavior in P. mirabilis through a distinct mechanism: selectively and transiently inducing non-self cells into a lifestyle incompatible with cooperative swarming. This state is characterized by reduced expression of genes associated with protein synthesis, virulence, and motility, and also causes non-self cells to tolerate previously lethal concentrations of antibiotics. We found that entry into this state requires a temporary activation of the stringent response in non-self cells and results in the iterative exclusion of non-self cells as a swarm colony migrates outwards. These data clarify the intricate connection between non-lethal recognition and the lifecycle of P. mirabilis swarm colonies.
Anatomical diversification of a skeletal novelty in bat feet
Authors: Stanchak Kathryn E. , Arbour Jessica H. , Santana Sharlene E.
Published: December 2018

Neomorphic, 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

B-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.
Embryo geometry drives formation of robust signaling gradients through receptor localization
Authors: Zhang Zhechun , Zwick Steven , Loew Ethan , Grimley Joshua S , Ramanathan Sharad
Published: December 2018

Morphogen signals are essential for cell fate specification during embryogenesis. Some receptors that sense these morphogen signals are known to localize to only the apical or basolateral membrane of polarized cell lines in vitro. How such localization affects morphogen sensing and patterning in the developing embryo remains unknown. Here, we show in the early mouse embryo that the formation of a robust BMP signaling gradient depends on restricted, basolateral localization of the BMP receptors. Mis-localizing these receptors to apical membrane leads to ectopic BMP signaling in the mouse embryo. To reach the basolaterally localized receptors in epiblast, BMP4 ligand, secreted by the extra-embryonic ectoderm, has to diffuses through the narrow interstitial space between the epiblast and the underlying endoderm. This restricted, basolateral diffusion creates a signaling gradient. The embryo geometry further buffers the gradient from fluctuations in the levels of BMP4. Our results demonstrate the importance of receptor localization and embryo geometry in shaping morphogen signaling during embryogenesis.
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

The 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.
Symmetric Intralimb Transfer of Skilled Isometric Force Production
Authors: Rajan Vikram A , Hardwick Robert M , Celnik Pablo A
Published: December 2018

Motor control theories propose that the same motor plans can be employed by different effectors. Skills learned with one effector can therefore 'transfer' to others, which has potential applications in clinical situations. However, evidence from visuomotor adaptation suggests this effect is asymmetric; learning can be generalized from proximal-to-distal effectors (e.g. arm to hand), but not from distal-to-proximal effectors (e.g. hand to arm). We propose that skill learning may not be subject to this asymmetry, as it relies on multiple learning processes beyond error detection and correction. Participants learned a skill task involving the production of isometric forces. We assessed their ability to perform the task with the hand and arm. One group trained to perform the task using only their hand, while a second trained using only their arm. In a final assessment, we found that participants who trained with either effector improved their skill in performing the task with both their hand and arm. There was no change in a control group that did not train between assessments, indicating that gains were related to the training, not the multiple assessments. These results indicate that in contrast to visuomotor adaptation, motor skills can generalize from both proximal-to-distal and distal-to-proximal effectors. We propose this is due to differences in the processes underlying skill acquisition in comparison to visuomotor adaptation.
Identification of spatially variable genes with graph cuts
Authors: Zhang Ke , Feng Wanwan , Wang Peng
Published: December 2018

Single-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

Simulated 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 implementation

Code 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.
Deciphering complex metabolite mixtures by unsupervised and supervised substructure discovery and semi-automated annotation from MS/MS spectra
Authors: Rogers Simon , Wei Ong Cher , Wandy Joe , Ernst Madeleine , Ridder Lars , van der Hooft Justin J.J.
Published: December 2018

Complex metabolite mixtures are challenging to unravel. Mass spectrometry (MS) is a widely used and sensitive technique to obtain structural information on complex mixtures. However, just knowing the molecular masses of the mixture's constituents is almost always insufficient for confident assignment of the associated chemical structures. Structural information can be augmented through MS fragmentation experiments whereby detected metabolites are fragmented giving rise to MS/MS spectra. However, how can we maximize the structural information we gain from fragmentation spectra? We recently proposed a substructure-based strategy to enhance metabolite annotation for complex mixtures by considering metabolites as the sum of (bio)chemically relevant moieties that we can detect through mass spectrometry fragmentation approaches. Our MS2LDA tool allows us to discover - unsupervised - groups of mass fragments and/or neutral losses termed Mass2Motifs that often correspond to substructures. After manual annotation, these Mass2Motifs can be used in subsequent MS2LDA analyses of new datasets, thereby providing structural annotations for many molecules that are not present in spectral databases. Here, we describe how additional strategies, taking advantage of i) combinatorial in-silico matching of experimental mass features to substructures of candidate molecules, and ii) automated machine learning classification of molecules, can facilitate semi-automated annotation of substructures. We show how our approach accelerates the Mass2Motif annotation process and therefore broadens the chemical space spanned by characterized motifs. Our machine learning model used to classify fragmentation spectra learns the relationships between fragment spectra and chemical features. Classification prediction on these features can be aggregated for all molecules that contribute to a particular Mass2Motif and guide Mass2Motif annotations. To make annotated Mass2Motifs available to the community, we also present motifDB: an open database of Mass2Motifs that can be browsed and accessed programmatically through an API. MotifDB is integrated within ms2lda.org, allowing users to efficiently search for characterized motifs in their own experiments. We expect that with an increasing number of Mass2Motif annotations available through a growing database we can more quickly gain insight in the constituents of complex mixtures. That will allow prioritization towards novel or unexpected chemistries and faster recognition of known biochemical building blocks.
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

Eosinophilic 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.
Towards Spider Glue: Long-read scaffolding for extreme length and repetitious silk family genes AgSp1 and AgSp2 with insights into functional adaptation
Authors: Stellwagen Sarah D , Renberg Rebecca L
Published: December 2018

The aggregate gland glycoprotein glue coating the prey-capture threads of orb weaving and cobweb weaving spider webs is comprised of silk protein spidroins (spider fibroins) encoded by two members of the silk gene family. It functions to retain prey that make contact with the web, but differs from solid silk fibers as it is a viscoelastic, amorphic, wet adhesive that is responsive to environmental conditions. Most spidroins are extremely large, highly repetitive genes that are impossible to sequence using only short-read technology. We sequenced for the first time the complete genomic Aggregate Spidroin 1 (AgSp1) and Aggregate Spidroin 2 (AgSp2) glue genes of Argiope trifasciata by using error-prone long reads to scaffold for high accuracy short reads. The massive coding sequences are 42,270 bp (AgSp1) and 20,526 bp (AgSp2) in length, the largest silk genes currently described. The majority of the predicted amino acid sequence of AgSp1 consists of two similar but distinct motifs that are repeated ~40 times each, while AgSp2 contains ~48 repetitions of an AgSp1-similar motif, interspersed by regions high in glutamine. Comparisons of AgSp repetitive motifs from orb web and cobweb spiders show regions of strict conservation followed by striking diversification. Glues from these two spider families have evolved contrasting material properties in adhesion, extensibility, and elasticity, which we link to mechanisms established for related silk genes in the same family. Full-length aggregate spidroin sequences from diverse species with differing material characteristics will provide insights for designing tunable bio-inspired adhesives for a variety of unique purposes.
From: Benjamin Lemasson Parametric response mapping as a new MRI approach for the characterization of posttraumatic cerebral edema
Authors: Greze Jules , Bouzat Pierre , Payen de la Garanderie Jean François , Barbier Emmanuel , Lemasson Benjamin
Published: December 2018

Purpose Cerebral edema is usually assessed with mean ADC value obtained with MRI. We aimed to use parametric response mapping (PRM), a voxel-based analysis, in a rat model of traumatic brain injury (TBI) to characterize the cerebral edema and to compare findings to those obtained with the classical global mean ADC analysis. Ultimately we wished to test whether early PRM analysis could identify the vasogenic or cellular edematous pattern two hours after trauma. Materials and Methods Experiments were conducted in a rat model of TBI in accordance with French Government guidelines. Eighteen traumatic brain-injured rats (TBI group) were compared to 7 sham-operated rats (Sham group). Diffusion-weighted images were acquired before and immediately (H0), 60min (H1) and 120min (H2) after the trauma. Two regions of interest (ROI) including cortex (cortical-ROI) and the whole brain (brainROI) were manually delineated. Results Averaged ADC value in cortical-ROI was significantly reduced at H2 in the TBI group versus Sham group (715±24 vs 781±16 µm²/sec; p=0.04), not in brain-ROI (748±27 vs 801±18 µm²/sec; p=0.32). By contrast, PRM values were significantly changed in these two ROIs at as soon as H1 in the TBI group (27.5±4% of the voxels beyond the PRM threshold in TBI group vs 5.1±1% in sham group; p<0.01). PRM was able to identify the nature of post traumatic cerebral edema: vasogenic, cellular or mixed pattern. ADC data obtained immediately after TBI and analyzed using PRM correlated with ADC data obtained at H2. Conclusion The PRM approach is more sensitive than averaged ADC at detecting and identifying post-traumatic brain edema. It is able to PRM might be a promising tool to individualize the management of patients with posttraumatic brain edema.
Assessment of Adherence to Antiretroviral Therapy Among Adult People Living with HIV/AIDS in North East, Ethiopia
Authors: Mengistie Almaz , Birhane Adugnaw , Tesfahun Esubalew ,   Adugnaw Birhane and Esubalew Tesfahun
Published: December 2018

Back ground

The scale-up of anti retroviral treatment is among the greatest successes of the global Acquired Immunodeficiency Syndromes (AIDS) response to date and it is on a Fast-Track- approach. To contribute to the global and local target of HIV /AIDS response as well as to obtain full benefits of ART medication, strong adherence of ≥95% to Anti-Retroviral Therapy (ART) is needed.

Methods

A cross-sectional study among 352 and 20 study participants for quantitative and for in-depth interview respectively. Data was collected using semi-structured questionnaire with a face-to-face interview for quantitative and interview guide for the in-depth interview. Bivariate and Multivariable logistic analysis was applied to examine the association between the dependent and independent variables. Additionally, thematic analysis, interpretation and triangulation of the finding were done for in-depth-interview.

Results

A total of 352 people living with HIV/AIDS were responded to the study with 90% response rate. Of the total 352 respondents 87.2% were adherent and the overall adherence level was found to be 95%. The study revealed factors associated to adherence to ART were marital status(AOR:4.4;95%CI:1.3-14.7), use of memory aids (AOR:6.5;95%CI:2.6-16.2) Living condition (AOR: 2.9;95%CI: 1.1-7.6), Experienced side effect (AOR: 4.6;95%CI;1.9-11.3),drug regimen (AOR: 5.5; 95%CI: 1.4-22.3) and distance in km (AOR:2.7;95% CI; 1.11-6.4).

Conclusion

Patient counselling, health education and health system strengthening are very important for improvement of ART drug adherence.
To examine environmental pollution by economic growth and their impact in an environmental Kuznets curve (EKC) among developed and developing countries.
Authors: Kong YuSheng , Khan Rabnawaz
Published: December 2018

This study analyzes the core energy consumption among countries specific variables by Environmental Kuznets Curve hypothesis (EKC), for a panel data of 29 (14 developed and 15 developing) countries during the period of 1977-2014. By assessing Generalized Method of Moments (GMM) regressions with first generation test such as common root, individual Augmented Dickey-Fuller (ADF), and individual root-Fisher-PP have been computed individually, the results confirm the EKC hypothesis in the case of emissions of solid, liquid, gases, manufacturing industries and also construction. Hence, we computed the cointegration test by Pedroni Kao from Engle-Granger based and Fisher. Onward, since the variable are co-integrated, a panel vector error correction model is estimated in GDP per capita, emission from manufacturing industries, arms import, commercial service export and coal rent, order to perform Pairwise Granger Causality test and indicate Vector Error Correction (VEC), with co-integration restrictions. Moreover, the statistical finding from VEC short-run unidirectional causality from GDP per capita growth to manufacturing industries and coat rent, as well as the causal link with manufacturing industries and commercial service export. Additionally, since there occurred no causal link among economic growth, arm import and coal rent.
Recovery from fire affects spatial variability of nutrient availability in boreal aspen ecosystems
Authors: Das Gupta Sanatan , MacKenzie M. Derek
Published: December 2018

Fire is a key driver of nutrient biogeochemistry in boreal ecosystems. Although a significant amount of research has been conducted to understand boreal fire ecology, it is still unclear how fire affects the spatial distribution of nutrients and what mechanisms are responsible for the post-fire recovery of spatial patterns. In this study, we examined spatial variability in soil nutrient bioavailability and related aboveground (AG) and belowground (BG) properties in three boreal aspen (Populus tremuloides Michx.) stands in northern Alberta at different stages of post-fire recovery. The studied sites include a 1-year old post fire stand (PF), a 9-year old stand at canopy closure (CC), and a 72-year old mature stand (MA). Ion exchange resin was used to measure nutrient bioavailability in-situ and was related to AG (vegetation and forest floor characteristics) and BG (soil microbial and chemical) properties. Significant spatial patterns were found in all three stands. PF stand had the greatest coarse scale spatial patterns (> 23 m) and availability of major macronutrients (N, P, and K). Shorter spatial range (5 to 10 m) of nutrient availability was observed in the stand with longest time since fire. Soil microbial activity was the strongest driver of nutrient availability in the PF stand, whereas contributions from aboveground variables such as understory vegetation, tree canopy cover, coarse woody debris (CWD), distance to nearest tree, and tree size was observed only in the CC and MA stands. The findings from the current study suggest that post-fire nutrient availability follows spatially predictable patterns, and confirm the hypothesis that stand replacing fire creates uniformity in nutrient availability and that the development of post-fire heterogeneity is a product of increasing ecosystem complexity.
Reserve size and anthropogenic disturbance affect the density of an African leopard (Panthera pardus) meta-population
Authors: Havmøller Rasmus Worsøe , Tenan Simone , Scharff Nikolaj , Rovero Francesco
Published: December 2018

Determining correlates of density for large carnivores is important to understand their ecological requirements and develop conservation strategies. Of the several earlier density studies conducted, few were done at a scale that allows inference about the correlates of density over heterogeneous landscapes. We deployed 164 camera trap stations covering ~2500 km2 across five distinct habitats in the Udzungwa Mountains, Tanzania, to investigate correlates of density for a widespread and adaptable carnivore, the leopard (Panthera pardus). We modelled data in a capture-recapture framework, with both biotic and abiotic covariates hypothesised to influence leopard density. We found that leopard density increased with distance to protected area borders (mean±SE estimated effect = 0.44±0.20), a proxy for both protected area extent and distance from surrounding human settlements. Second, we detected a weak positive relationship between leopard density and estimated mean prey occupancy, while density was not related to habitat type. We estimated mean leopard density at 3.84 individuals/100km2 (95% CI = 2.53 ? 5.85/100km2), with relatively moderate variation across habitat types. These results indicate that protected habitat extent and anthropogenic disturbance seemingly limit leopard populations more than prey abundance or habitat type. Such vulnerability is relevant to the conservation of this carnivore, which is generally considered more resilient to human disturbance than other large cats. Our findings support the notion that protected areas are important to preserve viable population of leopards, increasingly so in times of unprecedented habitat fragmentation. Protection of buffer zones smoothing the abrupt impact of human activities at reserve edges also appears of critical conservation relevance.
Tracking Pseudomonas aeruginosa transmissions due to environmental contamination after discharge in ICUs using mathematical models
Authors: Pham Thi Mui , Kretzschmar Mirjam , Bootsma Martin , Bertrand Xavier ,   COMBACTE-MAGNET Consortium
Published: December 2018

Pseudomonas aeruginosa (P. aeruginosa) is an important cause of healthcare-associated infections, particularly in immunocompromised patients. Understanding how this multi-drug resistant pathogen is transmitted within intensive care units (ICUs) is crucial for devising and evaluating successful control strategies. While it is known that moist environments serve as natural reservoirs for P. aeruginosa, there is little quantitative evidence regarding the contribution of environmental contamination to its transmission within ICUs. Previous studies on other nosocomial pathogens rely on deploying specific values for environmental parameters derived from costly and laborious genotyping. Using solely longitudinal surveillance data, we estimated the relative importance of P. aeruginosa transmission routes by exploiting the fact that different routes cause different pattern of fluctuations in the prevalence.

We developed a mathematical model including endogenous colonization, cross-transmission and environmental contamination. Patients contribute to a pool of pathogens by shedding bacteria to the environment. Natural decay and cleaning of the environment lead to a reduction of that pool. By assigning the bacterial load shed during an ICU stay to cross-transmission, we were able to disentangle environmental contamination during and after a patient’s stay.

Based on a data-augmented Markov Chain Monte Carlo method the relative importance of the considered acquisition routes is determined for two ICUs of the University hospital in Besancon (France). We used information about the admission and discharge days, screening days and screening results of the ICU patients.

Both cross-transmission and endogenous transmission play a significant role in the transmission process in both ICUs. In contrast, only about $1\%$ of the total transmissions were due to environmental contamination after discharge.

Improved cleaning of the environment after discharge would have only a limited impact regarding the prevention of P. aeruginosa infections in the two considered ICUs. Our model was developed for P. aeruginosa but can be easily applied to other pathogens as well.
Invariant neural responses for sensory categories revealed by the time-varying information for communication calls
Authors: Elie Julie Estelle , Theunissen Frederic E
Published: December 2018

Although information theoretic approaches have been used extensively in the analysis of the neural code, they have yet to be used to describe how information is accumulated in time while sensory systems are categorizing dynamic sensory stimuli such as speech sounds or visual objects. Here, we present a novel method to estimate the cumulative information for stimuli or categories. We further define a time-varying categorical information index that, by comparing the information obtained for stimuli versus categories of these same stimuli, quantifies invariant neural representations. We use these methods to investigate the dynamic properties of avian cortical auditory neurons recorded in zebra finches that were listening to a large set of call stimuli sampled from the complete vocal repertoire of this species. We found that the time-varying rates carry 5 times more information than the mean firing rates even in the first 100 ms. We also found that cumulative information has slow time constants (100-600 ms) relative to the typical integration time of single neurons, reflecting the fact that the behaviorally informative features of auditory objects are time-varying sound patterns. When we correlated firing rates and information values, we found that average information correlates with average firing rate but that higher-rates found at the onset response yielded similar information values as the lower-rates found in the sustained response: the onset and sustained response of avian cortical auditory neurons provide similar levels of independent information about call identity and call type. Finally, our information measures allowed us to rigorously define categorical neurons; these categorical neurons show a high degree of invariance for vocalizations within a call-type. Surprisingly, call-type invariant neurons were found in both primary and secondary avian auditory areas.
Pan-Cancer and Single-Cell modelling of genomic alterations through gene expression
Authors: Mercatelli Daniele , Ray Forest , Giorgi Federico M.
Published: December 2018

Cancer 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 Summary

In 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.
Mag2Pol: a program for the analysis of spherical neutron polarimetry, flipping ratio and integrated intensity data
Authors: Qureshi Navid
Published: December 2018

Mag2Pol is a graphical user interface program which is devoted to the treatment of data from polarized neutron diffractometers with spherical polarization analysis. Nuclear and magnetic structure models can be introduced using space-group symbols and individual symmetry operators, respectively, and viewed in an OpenGL widget. The program calculates nuclear/magnetic structure factors, flipping ratios and polarization matrices for magnetic Bragg reflections, taking into account structural twins and magnetic domains. Spherical neutron polarimetry data can be analyzed by refining a magnetic structure model including magnetic domain populations in a least-squares fit and can also be correlated with an integrated intensity data set in a joint refinement. Further features are the simultaneous refinement of nuclear and magnetic structures with integrated intensity data and the analysis of flipping ratios either with tabulated magnetic form factors or using a multipole expansion of the magnetization density.
Polar and non-polar structures of NH4TiOF3
Authors: Boytsova O. , Dovgaliuk I. , Chernyshov D. , Eliseev A. , O'Brien P. , Sutherland A. J. , Bosak A.
Published: December 2018

Ammonium oxofluorotitanate, NH4TiOF3, is probably the best known precursor for the synthesis of anatase mesocrystals. Transformation of NH4TiOF3 into TiO2 through thermal decomposition, accompanied by hydrolysis, preserves some structural features of the precursor. Currently, any discussion of the mechanism of this transformation is difficult, as the exact crystal structure of the starting compound is not available and no intermediate structures are known. This article describes the outcome of single-crystal and powder X-ray diffraction studies, revealing the existence of two polymorphs of the parent NH4TiOF3 at different temperatures. A second-order phase transition from the polar Pca21 α phase (1), stable at room temperature, to the Pma2 β phase (2) above ∼433 K has been demonstrated. The direction of the pseudo-fourfold axis in NH4TiOF3 coincides with the orientation of the fourfold axis of anatase mesocrystals, consistent with a topotactical transformation.
X-ray mirror surface figure correction with nanometre precision controlled by layer stresses simulated by FEA
Authors: Cheng Xianchao , Zhang Lin
Published: December 2018

Hard X-rays with energies higher than several kiloelectronvolts can be focused to spot sizes below 10 nm with the present synchrotron beamlines, offering unique advantages for the chemical, elemental and structure analysis of matter. Nevertheless, a surface precision on the nanometre scale for the focusing optics is required and remains the main hurdle limiting X-ray analytical techniques with single-nanometre spatial resolution. On the other hand, to preserve the wavefront properties of coherent X-ray beams, precise control of the reflective mirror surface quality at the nanometre scale is demanded for X-ray free-electron laser applications. In this work, the surface shape of a multilayer-coated X-ray mirror is controlled by layer stresses. The desired surface profile of the mirror is differentiated to its second order to obtain its corresponding curvature profile. With a step size of 1 mm along the mirror length, different coating thicknesses are applied to create different layer thermal stresses from uniform temperature change. The mirror surface profile can be obtained by integrating the curvature profile to its second order and further corrected by moving constant values for the slope and height. The technical process is simulated by finite element analysis (FEA). A case study showed that the residual slope error and the residual height error between the desired shape and the FEA result are 0.22 µrad (r.m.s.) and 1.42 nm (r.m.s.), respectively.