bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning modeling of Wigner intracule functionals for two electrons in one-dimension
Authors: Bhavsar Rutvij , Ramakrishnan Raghunathan
Published: April 2019

In principle, many-electron correlation energy can be precisely computed from a reduced Wigner distribution function (W), thanks to a universal functional transformation (F), whose formal existence is akin to that of the exchange-correlation functional in density functional theory. While the exact dependence of F on W is unknown, a few approximate parametric models have been proposed in the past. Here, for a dataset of 923 one-dimensional external potentials with two interacting electrons, we apply machine learning to model F within the kernel Ansatz. We deal with over-fitting of the kernel to a specific region of phase-space by a one-step regularization not depending on any hyperparameters. Reference correlation energies have been computed by performing exact and Hartree–Fock calculations using discrete variable representation. The resulting models require W calculated at the Hartree–Fock level as input while yielding monotonous decay in the predicted correlation energies of new molecules reaching sub-chemical accuracy with training.
Multiscale analysis of the effect of surface charge pattern on a nanopore’s rectification and selectivity properties: From all-atom model to Poisson-Nernst-Planck
Authors: Valiskó Mónika , Matejczyk Bartłomiej , Ható Zoltán , Kristóf Tamás , Mádai Eszter , Fertig Dávid , Gillespie Dirk , Boda Dezső
Published: April 2019

We report a multiscale modeling study for charged cylindrical nanopores using three modeling levels that include (1) an all-atom explicit-water model studied with molecular dynamics, and reduced models with implicit water containing (2) hard-sphere ions studied with the Local Equilibrium Monte Carlo simulation method (computing ionic correlations accurately), and (3) point ions studied with Poisson-Nernst-Planck theory (mean-field approximation). We show that reduced models are able to reproduce device functions (rectification and selectivity) for a wide variety of charge patterns, that is, reduced models are useful in understanding the mesoscale physics of the device (i.e., how the current is produced). We also analyze the relationship of the reduced implicit-water models with the explicit-water model and show that diffusion coefficients in the reduced models can be used as adjustable parameters with which the results of the explicit- and implicit-water models can be related. We find that the values of the diffusion coefficients are sensitive to the net charge of the pore but are relatively transferable to different voltages and charge patterns with the same total charge.
New monolayer material adds organic flexibility to spintronic technology
Authors: Liebendorfer Adam
Published: April 2019

Combining organic spin valves with alloys, researchers have created a platform with magnetoresistive and memristive traits that could pave the way for electric, magnetic and even optic manipulation.
Gasification of coal and biomass as a net carbon-negative power source for environment-friendly electricity generation in China
Authors: Lu Xi , Cao Liang , Wang Haikun , Peng Wei , Xing Jia , Wang Shuxiao , Cai Siyi , Shen Bo , Yang Qing , Nielsen Chris P. , McElroy Michael B.
Published: April 2019

Significance

Deploying coal-bioenergy gasification systems with carbon capture and storage (CBECCS) provides a promising opportunity for China to realize its carbon mitigation and air pollution abatement goals simultaneously. We conducted a comprehensive assessment of CBECCS technology for China, with a focus on plant and fuel configurations (e.g., biomass ratios) and economics, as well as CO2and greenhouse gas emissions and cobenefits for air quality. We find significant opportunities for carbon mitigation with air quality cobenefits from deployment of CBECCS systems in regions that are both rich in crop residues and facing urgent needs to curb serious air pollution. The study thus provides critical information for policy makers seeking to exploit the carbon-negative energy opportunities of CBECCS technology.
Structural insights into unique features of the human mitochondrial ribosome recycling
Authors: Koripella Ravi K. , Sharma Manjuli R. , Risteff Paul , Keshavan Pooja , Agrawal Rajendra K.
Published: April 2019

Mammalian mitochondrial ribosomes (mitoribosomes) are responsible for synthesizing proteins that are essential for oxidative phosphorylation (ATP generation). Despite their common ancestry with bacteria, the composition and structure of the human mitoribosome and its translational factors are significantly different from those of their bacterial counterparts. The mammalian mitoribosome recycling factor (RRF
mt
) carries a mito-specific N terminus extension (NTE), which is necessary for the function of RRF
mt
. Here we present a 3.9-Å resolution cryo-electron microscopic (cryo-EM) structure of the human 55S mitoribosome-RRF
mt
complex, which reveals α-helix and loop structures for the NTE that makes multiple mito-specific interactions with functionally critical regions of the mitoribosome. These include ribosomal RNA segments that constitute the peptidyl transferase center (PTC) and those that connect PTC with the GTPase-associated center and with mitoribosomal proteins L16 and L27. Our structure reveals the presence of a tRNA in the pe/E position and a rotation of the small mitoribosomal subunit on RRF
mt
binding. In addition, we observe an interaction between the pe/E tRNA and a mito-specific protein, mL64. These findings help understand the unique features of mitoribosome recycling.
Ebolavirus polymerase uses an unconventional genome replication mechanism
Authors: Deflubé Laure R. , Cressey Tessa N. , Hume Adam J. , Olejnik Judith , Haddock Elaine , Feldmann Friederike , Ebihara Hideki , Fearns Rachel , Mühlberger Elke
Published: April 2019

Significance

Ebolaviruses belong to the group of nonsegmented negative strand (NNS) RNA viruses. Most members of the
Ebolavirus
genus cause severe disease in humans. Here, we report that ebolaviruses have evolved a genome replication mechanism that distinguishes them from the other NNS RNA viruses. The ebolavirus replication strategy includes the addition of a nontemplated 3′ nucleotide at the genome ends which may aid in avoiding antiviral recognition. Our data highlight the need for more research on NNS RNA virus replication strategies to reveal commonalities between virus families as well as unique features. Dissecting the replication mechanisms of NNS RNA viruses, including ebolaviruses, paves the way for the development of broad-spectrum antivirals that target the viral replication complexes, thereby preventing virus amplification.
Targeted evolution of pinning landscapes for large superconducting critical currents
Authors: Sadovskyy Ivan A. , Koshelev Alexei E. , Kwok Wai-Kwong , Welp Ulrich , Glatz Andreas
Published: April 2019

Significance

Lossless transport is the Holy Grail of energy science in general and superconductivity research in particular. The main obstacle is the dissipative motion of Abrikosov vortices, which can be reduced or eliminated by pinning at nonsuperconducting defects. Pinning effectiveness nontrivially depends on various factors such as the shape, concentration, and spatial distribution of defects, rendering the optimization of the vortex pinning landscape highly difficult. Here, we use concepts from biological evolution to develop an efficient strategy for vortex pinning improvement. We replace natural selection with targeted selection, where only pinning configurations with better vortex immobilization survive. In combination with high-performance numerical algorithms, it allows us to dynamically evolve the defect landscape into the best possible pinning configuration with maximal lossless current.
Untangling posterior growth and segmentation by analyzing mechanisms of axis elongation in hemichordates
Authors: Fritzenwanker Jens H. , Uhlinger Kevin R. , Gerhart John , Silva Elena , Lowe Christopher J.
Published: April 2019

Significance

Comparative developmental studies from the segmented phyla, arthropods and chordates, has led to speculation that mechanistic coupling of posterior growth and segmentation is an ancient character of bilaterian trunk development. However, many phyla are characterized by animals with long unsegmented trunks. Currently, there are no functional studies that have investigated the mechanistic basis of trunk elongation in these phyla, which is crucial for making firm conclusions about the relationship of conserved regulatory networks and ancestral trunk morphological organization. Our results, together with results from protostomes, challenge hypotheses suggesting that the ancestral bilaterian trunk must have been segmented and highlight the flexibility of developmental programs in organismal evolution.
Chemosynthetic symbiont with a drastically reduced genome serves as primary energy storage in the marine flatworm
Paracatenula
Authors: Jäckle Oliver , Seah Brandon K. B. , Tietjen Målin , Leisch Nikolaus , Liebeke Manuel , Kleiner Manuel , Berg Jasmine S. , Gruber-Vodicka Harald R.
Published: April 2019

Hosts of chemoautotrophic bacteria typically have much higher biomass than their symbionts and consume symbiont cells for nutrition. In contrast to this, chemoautotrophic
Candidatus
Riegeria symbionts in mouthless
Paracatenula
flatworms comprise up to half of the biomass of the consortium. Each species of
Paracatenula
harbors a specific
Ca
. Riegeria, and the endosymbionts have been vertically transmitted for at least 500 million years. Such prolonged strict vertical transmission leads to streamlining of symbiont genomes, and the retained physiological capacities reveal the functions the symbionts provide to their hosts. Here, we studied a species of
Paracatenula
from Sant’Andrea, Elba, Italy, using genomics, gene expression, imaging analyses, as well as targeted and untargeted MS. We show that its symbiont,
Ca
. R. santandreae has a drastically smaller genome (1.34 Mb) than the symbiont´s free-living relatives (4.29–4.97 Mb) but retains a versatile and energy-efficient metabolism. It encodes and expresses a complete intermediary carbon metabolism and enhanced carbon fixation through anaplerosis and accumulates massive intracellular inclusions such as sulfur, polyhydroxyalkanoates, and carbohydrates. Compared with symbiotic and free-living chemoautotrophs,
Ca
. R. santandreae’s versatility in energy storage is unparalleled in chemoautotrophs with such compact genomes. Transmission EM as well as host and symbiont expression data suggest that
Ca
. R. santandreae largely provisions its host via outer-membrane vesicle secretion. With its high share of biomass in the symbiosis and large standing stocks of carbon and energy reserves, it has a unique role for bacterial symbionts—serving as the primary energy storage for its animal host.
Histone H3 tail binds a unique sensing pocket in EZH2 to activate the PRC2 methyltransferase
Authors: Jani Krupa S. , Jain Siddhant U. , Ge Eva J. , Diehl Katharine L. , Lundgren Stefan M. , Müller Manuel M. , Lewis Peter W. , Muir Tom W.
Published: April 2019

Significance

Polycomb Repressor Complex 2 (PRC2) is an epigenetic effector enzyme with key roles in gene silencing and establishment of facultative heterochromatin. Mutations of this histone lysine methyltransferase and its substrate H3K27 are linked to multiple human pathologies, and PRC2 has been identified as a therapeutic target in cancer treatment. The H3K27 methylation activity of PRC2 is sensitive to the chromatin environment, including the methylation state of H3K36 on the same histone tail. The mechanistic basis of this negative cross-talk is poorly understood. The present work sheds light on this question by identifying a regulatory feature on the catalytic subunit of PRC2, EZH2, which acts as a specific sensor for H3K36 methylation state. The work reveals an unusual mode of enzyme modulation by a substrate molecule.
Blind tests of RNA–protein binding affinity prediction
Authors: Kappel Kalli , Jarmoskaite Inga , Vaidyanathan Pavanapuresan P. , Greenleaf William J. , Herschlag Daniel , Das Rhiju
Published: April 2019

Significance

RNA and protein molecules interact to perform translation, splicing, and other fundamental processes. These interactions are defined by their strength and specificity, but it remains infeasible to experimentally measure these properties for all biologically important RNA–protein complexes. Development of computational strategies for calculating RNA–protein energetics has been hindered by unique complexities of RNA–protein binding, particularly the propensity of RNA to adopt multiple conformations in the unbound state. We describe a method, Rosetta-Vienna RNP-ΔΔG, combining 3D structure modeling with RNA secondary structure-based energetic calculations to predict RNA–protein relative binding affinities. For several diverse systems and in rigorous blind tests, the accuracy of Rosetta-Vienna RNP-ΔΔG compared with experimental measurements is significantly better than that of prior approaches.
Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial
Authors: Zubizarreta Irati , Flórez-Grau Georgina , Vila Gemma , Cabezón Raquel , España Carolina , Andorra Magi , Saiz Albert , Llufriu Sara , Sepulveda Maria , Sola-Valls Nuria , Martinez-Lapiscina Elena H. , Pulido-Valdeolivas Irene , Casanova Bonaventura , Martinez Gines Marisa , Tellez Nieves , Oreja-Guevara Celia , Español Marta , Trias Esteve , Cid Joan , Juan Manel , Lozano Miquel , Blanco Yolanda , Steinman Lawrence , Benitez-Ribas Daniel , Villoslada Pablo
Published: April 2019

Significance

Application of antigen-specific immune tolerance in autoimmune disease is a long-sought goal. We studied diseases with abundant information on the autoimmune target: in multiple sclerosis (MS), various myelin antigens are known targets of T cells and antibodies, whereas in neuromyelitis optica (NMO), the aquaporin-4 channel is attacked by T cells and antibodies. We tested whether engineered dendritic cells might induce a tolerogenic immune response in these two conditions. In this in-human clinical study, individual regulatory T cells, secreting IL-10, a key tolerogenic cytokine, were detected after treatment. These results might lead to more extensive trials with this approach in autoimmune conditions where the antigenic target has been identified, including MS, NMO, myasthenia gravis, and Graves disease.
Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen
Authors: Deak Peter E. , Kim Baksun , Abdul Qayum Amina , Shin Jaeho , Vitalpur Girish , Kloepfer Kirsten M. , Turner Matthew J. , Smith Neal , Shreffler Wayne G. , Kiziltepe Tanyel , Kaplan Mark H. , Bilgicer Basar
Published: April 2019

Significance

IgE antibody interaction with allergen proteins is the main driver for life-threating allergic responses. Using a nanoparticle-based method, we identified the most crucial binding sites for IgEs on peanut proteins by testing a small population of patient serum with a clinical history of severe allergies to peanuts. We then synthesized inhibitors, we call covalent heterobivalent inhibitors, which specifically and permanently prevent IgEs from binding to peanut proteins and triggering allergic responses. This is significant as it seems that only a few binding sites on peanut allergen proteins drive allergic responses. Also, this is a functional example of selective IgE inhibition to a relevant food allergen and establishes cHBIs as a class of allergy therapeutics.
Differential expression of human tRNA genes drives the abundance of tRNA-derived fragments
Authors: Torres Adrian Gabriel , Reina Oscar , Stephan-Otto Attolini Camille , Ribas de Pouplana Lluís
Published: April 2019

The human genome encodes hundreds of transfer RNA (tRNA) genes but their individual contribution to the tRNA pool is not fully understood. Deep sequencing of tRNA transcripts (tRNA-Seq) can estimate tRNA abundance at single gene resolution, but tRNA structures and posttranscriptional modifications impair these analyses. Here we present a bioinformatics strategy to investigate differential tRNA gene expression and use it to compare tRNA-Seq datasets from cultured human cells and human brain. We find that sequencing caveats affect quantitation of only a subset of human tRNA genes. Unexpectedly, we detect several cases where the differences in tRNA expression among samples do not involve variations at the level of isoacceptor tRNA sets (tRNAs charged with the same amino acid but using different anticodons), but rather among tRNA genes within the same isodecoder set (tRNAs having the same anticodon sequence). Because isodecoder tRNAs are functionally equal in terms of genetic translation, their differential expression may be related to noncanonical tRNA functions. We show that several instances of differential tRNA gene expression result in changes in the abundance of tRNA-derived fragments (tRFs) but not of mature tRNAs. Examples of differentially expressed tRFs include PIWI-associated RNAs, tRFs present in tissue samples but not in cells cultured in vitro, and somatic tissue-specific tRFs. Our data support that differential expression of tRNA genes regulate noncanonical tRNA functions performed by tRFs.
Mechanistic basis for impaired ferroptosis in cells expressing the African-centric S47 variant of p53
Authors: Leu Julia I-Ju , Murphy Maureen E. , George Donna L.
Published: April 2019

Significance

The p53 tumor suppressor protein is a critical stress response mediator. Polymorphisms in the human TP53 gene can alter protein function. We investigated an African-centric variant affecting codon 47 (P47S). Compared with those with the P47 variant, cells and mice expressing the serine 47 (S47) variant exhibit increased levels of coenzyme A (CoA) and glutathione (GSH). These molecules inhibit the induction of ferroptosis in S47 cells and mice. Elevated levels of CoA and GSH feedback on the p53 protein to negatively regulate the structure and function of this tumor suppressor protein. We identify CoA as a regulator of ferroptosis and show that the control of cell fate in response to certain ferroptosis inducers and p53 is reversible by altering the redox environment.
Sexual conflict drives male manipulation of female postmating responses inDrosophila melanogaster
Authors: Hollis Brian , Koppik Mareike , Wensing Kristina U. , Ruhmann Hanna , Genzoni Eléonore , Erkosar Berra , Kawecki Tadeusz J. , Fricke Claudia , Keller Laurent
Published: April 2019

In many animals, females respond to mating with changes in physiology and behavior that are triggered by molecules transferred by males during mating. InDrosophila melanogaster, proteins in the seminal fluid are responsible for important female postmating responses, including temporal changes in egg production, elevated feeding rates and activity levels, reduced sexual receptivity, and activation of the immune system. It is unclear to what extent these changes are mutually beneficial to females and males or instead represent male manipulation. Here we use an experimental evolution approach in which females are randomly paired with a single male each generation, eliminating any opportunity for competition for mates or mate choice and thereby aligning the evolutionary interests of the sexes. After >150 generations of evolution, males from monogamous populations elicited a weaker postmating stimulation of egg production and activity than males from control populations that evolved with a polygamous mating system. Males from monogamous populations did not differ from males from polygamous populations in their ability to induce refractoriness to remating in females, but they were inferior to polygamous males in sperm competition. Mating-responsive genes in both the female abdomen and head showed a dampened response to mating with males from monogamous populations. Males from monogamous populations also exhibited lower expression of genes encoding seminal fluid proteins, which mediate the female response to mating. Together, these results demonstrate that the female postmating response, and the male molecules involved in eliciting this response, are shaped by ongoing sexual conflict.
Early tropical crop production in marginal subtropical and temperate Polynesia
Authors: Prebble Matthew , Anderson Atholl J. , Augustinus Paul , Emmitt Joshua , Fallon Stewart J. , Furey Louise L. , Holdaway Simon J. , Jorgensen Alex , Ladefoged Thegn N. , Matthews Peter J. , Meyer Jean-Yves , Phillipps Rebecca , Wallace Rod , Porch Nicholas
Published: April 2019

Significance

Fossil evidence shows that Polynesians introduced the tropical crop taro (Colocasia esculenta) during initial colonization of the subtropical South Pacific islands and temperate New Zealand after 1200 CE, establishing garden ecosystems with similar commensal plants and invertebrates. Sedimentary charcoal and fossil remains indicate how frequent burning and perennial cultivation overcame the ecological constraints for taro production, particularly the temperate forest cover of New Zealand. An increase in short-lived plants, indicating a transition toward higher-intensity production, followed rapid woody forest decline and species extinctions on all islands. The relatively recent fossil records from the subtropical and temperate islands of Polynesia provide unique insights into the ecological processes behind the spread of Neolithic crops into areas marginal for production.
Myosin Va transport of liposomes in three-dimensional actin networks is modulated by actin filament density, position, and polarity
Authors: Lombardo Andrew T. , Nelson Shane R. , Kennedy Guy G. , Trybus Kathleen M. , Walcott Sam , Warshaw David M.
Published: April 2019

Significance

Intracellular transport of critical cellular components (e.g. vesicles, organelles, mRNA, chromosomes) is accomplished by myosin Va molecular motors along complicated 3D networks of actin filaments. Disruption of these transport processes leads to debilitating human disease (e.g. Griscelli syndrome), while rearrangement of the 3D actin cytoskeleton is a hallmark of malignant cancers. We found that the various modes of motion (stationary, diffusive-like, or directed) describing how teams of myosin Va transport 350-nm liposome cargos are determined by the 3D position and polarity of the actin filaments within the network that the myosin Va motors interact with. This study demonstrates that the 3D actin filament organization within the network can serve as a potent regulator of myosin Va motor-based intracellular transport.
Genomic evidence of survival near ice sheet margins for some, but not all, North American trees
Authors: Bemmels Jordan B. , Knowles L. Lacey , Dick Christopher W.
Published: April 2019

Temperate species experienced dramatic range reductions during the Last Glacial Maximum, yet refugial populations from which modern populations are descended have never been precisely located. Climate-based models identify only broad areas of potential habitat, traditional phylogeographic studies provide poor spatial resolution, and pollen records for temperate forest communities are difficult to interpret and do not provide species-level taxonomic resolution. Here we harness signals of range expansion from large genomic datasets, using a simulation-based framework to infer the precise latitude and longitude of glacial refugia in two widespread, codistributed hickories (Caryaspp.) and to quantify uncertainty in these estimates. We show that one species likely expanded from close to ice sheet margins near the site of a previously described macrofossil for the genus, highlighting support for the controversial notion of northern microrefugia. In contrast, the expansion origin inferred for the second species is compatible with classic hypotheses of distant displacement into southern refugia. Our statistically rigorous, powerful approach demonstrates how refugia can be located from genomic data with high precision and accuracy, addressing fundamental questions about long-term responses to changing climates and providing statistical insight into longstanding questions that have previously been addressed primarily qualitatively.
The Hunt for Non-Barking Dogs and Other Curiosities: Identifying and Managing Anomaly Within Forensic Interviews
Authors: Shepherd Eric
Published: April 2019

Purposeful conversation—interviewing—is a core activity for forensic practitioners. It is fundamental to investigation, assessment, decision-making, and action. This contribution seeks to enhance practitioner performance in the identification and management of anomaly occurring within forensic interviews, and the clinical context in particular. A review of anomaly in conversation precedes an examination of anomaly occurring at points across the course of a conversation that the professional manages to achieve an investigative aim by introducing, or responding to, specific issues or topics. Termed hot spots the occurrence of verbal anomaly, nonverbal anomaly, or both evidence the sensitivity of the topic or issue. A number of practitioner aids are presented: a framework for identifying and managing verbal anomaly in interviews; a framework for initial assessment and subsequent monitoring of an interviewee’s nonverbal behavior; and conversation management techniques aimed at maximizing interviewee disclosure, the interviewee’s occupancy of the talking turn, and the practitioner’s potential to apply the two frameworks for monitoring anomaly to enable the detection of hot spots that require timely probing.
Effective detection of spatio-temporal carrier dynamics by carrier capture
Authors: Rosati R , Lengers F , Reiter D E , Kuhn T
Published: April 2019

The spatio-temporal dynamics of electrons moving in a 2D plane is challenging to detect when the required resolution shrinks simultaneously to nanometer length and subpicosecond time scale. We propose a detection scheme relying on phonon-induced carrier capture from 2D unbound states into the bound states of an embedded quantum dot. This capture process happens locally and here we explore if this locality is sufficient to use the carrier capture process as detection of the ultrafast diffraction of electrons from an obstacle in the 2D plane. As an example we consider an electronic wave packet traveling in a semiconducting monolayer of the transition metal dichalcogenide MoSe2, and we study the scattering-induced dynamics using a single particle Lindblad approach. Our results offer a new way to high resolution detection of the spatio-temporal carrier dynamics.
Noise spectroscopy to study the 1D electron transport properties in InAs nanowires
Authors: Petrychuk M , Zadorozhnyi I , Kutovyi Y , Karg S , Riel H , Vitusevich S
Published: April 2019

InAs nanowires (NWs) are recognized as a key material due to their unique transport properties. Despite remarkable progress in designing InAs NW device structures, there are still open questions on device variability. Here, we demonstrate that noise spectroscopy allows us to study not only the parameters of traps, but also to shed light on quantum transport in NW structures. This provides an important understanding of structural behavior as well as the background and strategy required to design NW structures with advanced properties.
Principal component analysis for fast and model-free denoising of multi b-value diffusion-weighted MR images
Authors: Gurney-Champion Oliver J , Collins David J , Wetscherek Andreas , Rata Mihaela , Klaassen Remy , van Laarhoven Hanneke W M , Harrington Kevin J , Oelfke Uwe , Orton Matthew R
Published: April 2019

Despite the utility of tumour characterisation using quantitative parameter maps from multi-b-value diffusion-weighted MRI (DWI), clinicians often prefer the use of the image with highest diffusion-weighting (b-value), for instance for defining regions of interest (ROIs). However, these images are typically degraded by noise, as they do not utilize the information from the full acquisition. We present a principal component analysis (PCA) approach for model-free denoising of DWI data. PCA-denoising was compared to synthetic MRI, where a diffusion model is fitted for each voxel and a denoised image at a given b-value is generated from the model fit. A quantitative comparison of systematic and random errors was performed on data simulated using several diffusion models (mono-exponential, bi-exponential, stretched-exponential and kurtosis). A qualitative visual comparison was also performed for in vivo images in six healthy volunteers and three pancreatic cancer patients. In simulations, the reduction in random errors from PCA-denoising was substantial (up to 55%) and similar to synthetic MRI (up to 53%). Model-based synthetic MRI denoising resulted in substantial (up to 29% of signal) systematic errors, whereas PCA-denoising was able to denoise without introducing systematic errors (less than 2%). In vivo, the signal-to-noise ratio (SNR) and sharpness of PCA-denoised images were superior to synthetic MRI, resulting in clearer tumour boundaries. In the presence of motion, PCA-denoising did not cause image blurring, unlike image averaging or synthetic MRI. Multi-b-value MRI can be denoised model-free with our PCA-denoising strategy that reduces noise to a level similar to synthetic MRI, but without introducing systematic errors associated with the synthetic MRI method.
Verbal Fluency Development Across Childhood: Normative Data from Brazilian–Portuguese Speakers and Underlying Cognitive Processes
Authors: Becker Natalia , Piccolo L R , Salles J F
Published: April 2019

Objective

Verbal fluency (VF) tasks are widely used to investigate children’s lexical knowledge and executive functions skills. Consistency of measurement of the strategic retrieval components is still an issue and performance of Brazilian–Portuguese speaking children are currently not available. A cross-sectional study investigated the effects of age, school type (public × private) and the influence of language, memory and inhibitory control on VF.

Method

We assessed 414 Brazilian children, aged 6–12, in the number of words produced and both clustering and switching components, with two measures of VF: letter (LVF) and semantic (SVF).

Results

Analysis of the number of words produced showed a significant increase between 6–8-year-olds, 9–10-year-olds and 11–12-year-olds in SVF, while in LVF, the differences were significant only in the later age group. In SVF, the numbers of clusters and switches increased with age, whereas in LVF, the number of switches increased in all age groups, but clusters increased only in the older group. Structural equation model analyses showed that oral and written language, verbal memory and inhibitory control are associated with VF performance and IQ, while age mediated VF performance.

Conclusions

The results indicate a different development pattern between LVF and SVF in the number of words produced and in clustering and switching, with the latter predicting VF performance in words produced. VF development is shown to depend on language, memory and inhibitory control. Our results have important implications to clinical neuropsychology.
SurVIndel: improving CNV calling from high-throughput sequencing data through statistical testing
Authors: Rajaby Ramesh , Sung Wing-Kin
Published: April 2019

Motivation

Structural variations (SVs) are large scale mutations in a genome; although less frequent than point mutations, due to their large size they are responsible for more heritable differences between individuals. Two prominent classes of SVs are deletions and tandem duplications. They play important roles in many devastating genetic diseases, such as Smith-Magenis syndrome, Potocki-Lupski syndrome and Williams-Beuren syndrome. Since paired-end whole genome sequencing data have become widespread and affordable, reliably calling deletions and tandem duplications has been a major target in bioinformatics; unfortunately, the problem is far from being solved, since existing solutions often offer poor results when applied to real data.

Results

We developed a novel caller, SurVIndel, which focuses on detecting deletions and tandem duplications from paired next-generation sequencing data. SurVIndel uses discordant paired reads, clipped reads as well as statistical methods. We show that SurVIndel outperforms existing methods on both simulated and real biological datasets.

Availability and implementation

SurVIndel is available at https://github.com/Mesh89/SurVIndel.

Supplementary information

Supplementary data are available at Bioinformatics online.
Hepatitis C Virus (HCV) Treatment With Directly Acting Agents Reduces the Risk of Incident Diabetes: Results From Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES)
Authors: Butt Adeel A , Yan Peng , Aslam Samia , Shaikh Obaid S , Abou-Samra Abdul-Badi
Published: April 2019

Background

The effects of interferon-based therapies for hepatitis C virus (HCV) upon the risk of diabetes are controversial. The effects of newer, directly acting antiviral agents (DAA) upon this risk are unknown. We sought to determine the effects of HCV treatment upon the risk and incidence of diabetes.

Methods

Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database for persons with chronic HCV infection (n = 242 680), we identified those treated with a pegylated interferon and ribavirin regimen (PEG/RBV, n = 4764) or a DAA-containing regimen (n = 21 279), after excluding those with diabetes at baseline, those with a human immunodeficiency virus or hepatitis B virus coinfection, and those treated with both PEG/RBV and DAA regimens. Age-, race-, sex-, and propensity score–matched controls (1:1) were also identified.

Results

Diabetes incidence rates per 1000 person-years were 20.6 (95% confidence interval [CI] 19.6–21.6) among untreated persons, 19.8 (95% CI 18.3–21.4) among those treated with PEG/RBV, and 9.89 (95% CI 8.7–11.1) among DAA-treated persons (P < .001). Among the treated, rates were 13.3 (95% CI 12.2–14.5) for those with a sustained virologic response (SVR) and 19.2 (95% CI 17.4–21.1) for those without an SVR (P < .0001). A larger reduction was observed in persons with more advanced fibrosis/cirrhosis (absolute difference 2.9 for fibrosis severity score [FIB-4] < 1.25; 5.7 for FIB-4 1.26–3.25; 9.8 for FIB-4 >3.25). DAA treatment (hazard ratio [HR] 0.53, 95% CI .46–.63) and SVR (HR 0.81, 95% CI .70–.93) were associated with a significantly reduced risk of diabetes. DAA-treated persons had longer diabetes-free survival rates, compared to untreated and PEG/RBV-treated persons. There was no significant difference in diabetes-free survival rates between untreated and PEG/RBV-treated persons. The results were similar in inverse probability of treatment and censoring weight models.

Conclusions

DAA therapy significantly reduces the incidence and risk of subsequent diabetes. Treatment benefits are more pronounced in persons with more advanced liver fibrosis.
Extant microbial communities in the partially desiccated Rincon de Parangueo maar crater lake in Mexico
Authors: Sánchez-Sánchez Janet , Cerca Mariano , Alcántara-Hernández Rocío J , Lozano-Flores Carlos , Carreón-Freyre Dora , Levresse Gilles , Vega Marina , Varela-Echavarría Alfredo , Aranda-Gómez Jose Jorge
Published: April 2019

Rincon de Parangueo is a maar where a perennial lake was present until the 1980s. A conspicuous feature of the lake’s sediments is the presence of bioherms and organo-sedimentary deposits produced by microbial communities. The gradual lake desiccation during the last 40 years has produced dramatic environmental changes inside the maar basin, which resulted in the formation of a highly saline-alkaline system with extant microorganisms. In this paper we succinctly describe the geologic setting where the microbial communities have developed inside of the maar crater and the results obtained from high-throughput sequencing methods to characterize the microbial component (Bacteria, Eukarya and Archaea) in endolithic mats of calcareous sediments, and microbial mats and free-living microorganisms in the soda ponds. The studied sites displayed different microbial communities with a diverse number of phylotypes belonging to Bacteria and Eukarya, contrasting with a much less diverse component in Archaea. The sequences here detected were related to environmental sequences from sites with extreme life conditions such as high alkalinity (alkaliphiles), high salinity (halophiles) and high temperature (thermophiles). Moreover, our results indicate an important unexplored endemic microbial biodiversity in the vestiges of the former lake that need to be studied.
The relationship between an electronic mental health stigma campaign and suicidal thoughts and behaviours: a two-arm randomized controlled trial in the Australian construction industry
Authors: Milner A , Aitken Z , Law P C F , LaMontagne A D , Mann C , Cooper T , Witt K
Published: April 2019

Males employed in the construction industry are at greater risk of suicide than other employed males. It is plausible that a high level of stigma against mental health problems explains the elevated rates of suicide among this group. This study sought to test the effectiveness of an electronic mental health stigma intervention on suicide ideation, communication about suicide and attempts. Participants were randomly assigned to receive either a series of brief contact interventions over a 6-week period or a wait list control. Suicidal ideation, communication about suicide and suicide attempts were assessed using the Suicidal Behaviors Questionnaire-Revised at post-intervention. We used linear regression to assess effectiveness at post-intervention, adjusting for relevant covariates using both conventional methods and a propensity score approach. Results indicate that the intervention had no significant impact on suicidal thoughts, communication or suicide attempts. There was some indication that individuals in the intervention group reported a slight increase in attempts and communication about suicide. These observations underscore an urgent need for more research to understand the complex and nuanced relationship between stigma and suicide in non-clinical populations.
On the Extremal Number of Subdivisions
Authors: Conlon David , Lee Joonkyung
Published: April 2019

One of the cornerstones of extremal graph theory is a result of Füredi, later reproved and given due prominence by Alon, Krivelevich, and Sudakov, saying that if $H$ is a bipartite graph with maximum degree $r$ on one side, then there is a constant $C$ such that every graph with $n$ vertices and $C n^{2 - 1/r}$ edges contains a copy of $H$. This result is tight up to the constant when $H$ contains a copy of $K_{r,s}$ with $s$ sufficiently large in terms of $r$. We conjecture that this is essentially the only situation in which Füredi’s result can be tight and prove this conjecture for $r = 2$. More precisely, we show that if $H$ is a $C_4$-free bipartite graph with maximum degree $2$ on one side, then there are positive constants $C$ and $\delta $ such that every graph with $n$ vertices and $C n^{3/2 - \delta }$ edges contains a copy of $H$. This answers a question of Erd̋s from 1988. The proof relies on a novel variant of the dependent random choice technique which may be of independent interest.
Short-course versus long-course antibiotics in prosthetic joint infections: a systematic review and meta-analysis of one randomized controlled trial plus nine observational studies
Authors: Yen Hung-Teng , Hsieh Ronan W , Huang Chung-yen , Hsu Tzu-Chun , Yeh Timothy , Chen Yee-Chun , Chen Wen-Shan , Lee Chien-Chang
Published: April 2019

Background

Prosthetic joint infections (PJIs) often require long-course antibiotic therapy. However, recent studies argue against the current practice and raise concerns such as the development of antibiotic resistance, side effects of medications and medical costs.

Objectives

To review and compare the outcomes of short-course and long-course antibiotics in PJIs.

Methods

We conducted a systemic review and meta-analysis using a predefined search term in PubMed and EMBASE databases. Studies that met the inclusion criteria from inception to June 2018 were included. The quality of the included studies was assessed.

Results

A total of 10 articles and 856 patients were analysed, comprising 9 observational studies and 1 randomized controlled trial. Our meta-analysis showed no significant difference between short-course and long-course antibiotics (relative risk = 0.87, 95% CI = 0.62–1.22). Additionally, the older the studied group was, the more short-course antibiotics were favoured.

Conclusions

When treating PJI patients following debridement, antibiotics and implant retention, an 8 week course of antibiotic therapy for total hip arthroplasty and a 75 day course for total knee arthroplasty may be a safe approach. For two-stage exchange, a shorter duration of antibiotic treatment during implant-free periods is also generally safe with the usage of antibiotic-loaded cement spacers.
Increased tenofovir monoester concentrations in patients receiving tenofovir disoproxil fumarate with ledipasvir/sofosbuvir
Authors: Brooks Kristina M , Castillo-Mancilla Jose R , Blum Joshua , Huntley Ryan , MaWhinney Samantha , Alexander Keisha , Kerr Becky Jo , Ellison Lucas , Bushman Lane R , MacBrayne Christine E , Anderson Peter L , Kiser Jennifer J
Published: April 2019

Background

Intracellular tenofovir diphosphate concentrations are markedly increased in HIV/HCV coinfected individuals receiving tenofovir disoproxil fumarate (TDF) with sofosbuvir-containing treatment. Sofosbuvir may inhibit the hydrolysis of TDF to tenofovir, resulting in increased concentrations of the disoproxil or monoester forms, which may augment cell loading. We sought to quantify tenofovir disoproxil and monoester concentrations in individuals receiving TDF with and without ledipasvir/sofosbuvir.

Methods

HIV/HCV coinfected participants receiving TDF-based therapy were sampled pre-dose and 1 and 4 h post-dose prior to and 4 weeks after initiating ledipasvir/sofosbuvir. Tenofovir disoproxil was not detectable. Tenofovir monoester in plasma and tenofovir diphosphate in PBMC and dried blood spots (DBS) were quantified using LC-MS/MS. Geometric mean ratios (week 4 versus baseline) and 95% CIs were generated for the pharmacokinetic parameters. P values reflect paired t-tests.

Results

Ten participants had complete data. At baseline, geometric mean (95% CI) tenofovir monoester plasma concentrations at 1 and 4 h post-dose were 97.4 ng/mL (33.0–287.5) and 0.74 ng/mL (0.27–2.06), respectively. With ledipasvir/sofosbuvir, tenofovir monoester concentrations at 4 h post-dose were 5.02-fold higher (95% CI 1.40–18.05; P = 0.019), but did not significantly differ at 1 h post-dose (1.72-fold higher, 95% CI 0.25–11.78; P = 0.54), possibly due to absorption variability. Tenofovir diphosphate in PBMC and DBS were increased 2.80-fold (95% CI 1.71–4.57; P = 0.001) and 7.31-fold (95% CI 4.47–11.95; P < 0.0001), respectively, after 4 weeks of ledipasvir/sofosbuvir.

Conclusions

Tenofovir monoester concentrations were increased in individuals receiving TDF with ledipasvir/sofosbuvir, consistent with inhibition of TDF hydrolysis. Additional studies are needed to determine the clinical relevance of this interaction.
Cost-Effectiveness of Colonoscopy-Based Colorectal Cancer Screening in Childhood Cancer Survivors
Authors: Gini Andrea , Meester Reinier G S , Keshavarz Homa , Oeffinger Kevin C , Ahmed Sameera , Hodgson David C , Lansdorp-Vogelaar Iris
Published: April 2019

Background

Childhood cancer survivors (CCS) are at increased risk of developing colorectal cancer (CRC) compared to the general population, especially those previously exposed to abdominal or pelvic radiation therapy (APRT). However, the benefits and costs of CRC screening in CCS are unclear. In this study, we evaluated the cost-effectiveness of early-initiated colonoscopy screening in CCS.

Methods

We adjusted a previously validated model of CRC screening in the US population (MISCAN-Colon) to reflect CRC and other-cause mortality risk in CCS. We evaluated 91 colonoscopy screening strategies varying in screening interval, age to start, and age to stop screening for all CCS combined and for those treated with or without APRT. Primary outcomes were CRC deaths averted (compared to no screening) and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold of $100 000 per life-years gained (LYG) was used to determine the optimal screening strategy.

Results

Compared to no screening, the US Preventive Services Task Force’s average risk screening schedule prevented up to 73.2% of CRC deaths in CCS. The optimal strategy of screening every 10 years from age 40 to 60 years averted 79.2% of deaths, with ICER of $67 000/LYG. Among CCS treated with APRT, colonoscopy every 10 years from age 35 to 65 years was optimal (CRC deaths averted: 82.3%; ICER: $92 000/LYG), whereas among those not previously treated with APRT, screening from age 45 to 55 years every 10 years was optimal (CRC deaths averted: 72.7%; ICER: $57 000/LYG).

Conclusions

Early initiation of colonoscopy screening for CCS is cost-effective, especially among those treated with APRT.
Citizens of Nowhere? Paradoxes of State Parental Responsibility for Unaccompanied Migrant Children in the United Kingdom
Authors: Meloni Francesca , Humphris Rachel
Published: April 2019

Social workers are confronted with a contradictory task: that of acting as state parents for unaccompanied asylum-seeking children, in an era of hostile migration policies and austerity. Mobilizing Young’s (2006) concept of ‘responsibility’, we ask: how is state parental responsibility towards unaccompanied minors given meaning, and with what consequences, for both frontline workers and unaccompanied minors alike? Drawing on interviews with frontline workers and unaccompanied minors in the United Kingdom (n = 107), we delineate three modes through which responsibility operates: namely outcomes, capacity and morality. We argue that the underlying logic of responsibility shifts the blame from sociopolitical structures to migrant children themselves, with crucial consequences for questions of social justice.
Dark molecular gas in Pegasus–Pisces
Authors: Donate Emmanuel , Blair Samantha , Chilton Zachary , Gladney Codie , Gordon Jeremy W , Goulart Micah C , Magnani Loris
Published: April 2019

We examine the molecular content of a large region (∼2200 square degrees) in Pegasus–Pisces with an estimated dark molecular gas fraction of 59 per cent. Using the extensive CO(1-0) Southern Galactic hemisphere, high-latitude survey by Magnani et al. (2000), we re-examined the CO-detectable mass estimates for the region. By averaging all the CO spectra in subsections ranging in size from 3° × 3° to 15° × 15°, we decreased the rms of the averaged CO spectra by factors of 3–10, effectively trading spatial resolution for sensitivity. With the new spectra, we are able to make estimates of the CO-detectable mass as a function of sensitivity. Using the optimal estimate, the CO-detectable mass increases from 2200 to 4000 M⊙, thereby decreasing the dark molecular gas fraction in the region to 0.24. CO(1–0) observations with rms values in the 20–30 mK range can nearly double the molecular mass in regions with diffuse and translucent molecular clouds.