bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the distributions of white dwarf atmospheric pollution: a low Mg abundance for accreted planetesimals?
Authors: Turner Samuel G D , Wyatt Mark C 
Published: November 2019

Abstract
The accretion of planetesimals onto white dwarf atmospheres allows determination of the composition of this polluting material. This composition is usually inferred from observed pollution levels by assuming it originated from a single body. This paper instead uses a stochastic model wherein polluting planetesimals are chosen randomly from a mass distribution, finding that the single body assumption is invalid in ${>20\%}$ of cases. Planetesimal compositions are modelled assuming parent bodies that differentiated into core, mantle and crust components. Atmospheric levels of Ca, Mg and Fe in the model are compared to a sample of 230 DZ white dwarfs for which such pollution is measured. A good fit is obtained when each planetesimal has its core, mantle and crust fractions chosen independently from logit-normal distributions which lead to average mass fractions of fCru = 0.15, fMan = 0.49 and fCor = 0.36. However, achieving this fit requires a factor 4 depletion of Mg relative to stellar material. This depletion is unlikely to originate in planetesimal formation processes, but might occur from heating while the star is on the giant branch. Alternatively the accreted material has stellar abundance, and either the inferred low Mg abundance was caused by an incorrect assumption that Mg sinks slower than Ca and Fe, or there are unmodelled biases in the observed sample. Finally, the model makes predictions for the timescale on which the observed pollutant composition varies, which should be the longer of the sinking and disc timescales, implying variability on decadal timescales for DA white dwarfs.
Translating current biomedical therapies for long duration, deep space missions
Authors: Iosim Sonia , MacKay Matthew , Westover Craig , Mason Christopher E 
Published: November 2019

Abstract
It is been shown that spaceflight-induced molecular, cellular, and physiologic changes cause alterations across many modalities of the human body, including cardiovascular, musculoskeletal, hematological, immunological, ocular, and neurological systems. The Twin Study, a multi-year, multi-omic study of human response to spaceflight, provided detailed and comprehensive molecular and cellular maps of the human response to radiation, microgravity, isolation, and stress. These rich data identified epigenetic, gene expression, inflammatory, and metabolic responses to spaceflight, facilitating a better biomedical roadmap of features that should be monitored and safe-guarded in upcoming missions. Further, by exploring new developments in pre-clinical models and clinical trials, we can begin to design potential cellular interventions for exploration-class missions to Mars and potentially farther. This paper will discuss the overall risks astronauts face during spaceflight, what is currently known about human response to these risks, what pharmaceutical interventions exist for use in space, and which tools of precision medicine and cellular engineering could be applied to aerospace and astronaut medicine.
Analytical investigations of high-energy electromagnetic showers in strong magnetic fields
Authors: Nakatsuka Takao 
Published: November 2019

Abstract
The diffusion equation of high-energy electromagnetic showers in strong magnetic fields is solved analytically, under the condition that the product of particle energy and field strength considerably exceeds $mc^2H_{\rm c}\simeq 2.3 \times 10^{7}$ TeV G, by applying Mellin and Laplace transforms. Differential and integral energy spectra of shower electrons/positrons and photons are evaluated by applying the saddle point method. Both spectra expressed by asymptotic expansions are also derived based on singularities of the Laplace–Mellin transform of the spectrum. The results are compared with those derived by a Monte Carlo method and numerical integration methods. Energy flows, peak positions, and peak values of transition curves, as well as track lengths of shower particles, are predicted and discussed, together with other characteristic properties of showers in strong magnetic fields, wherein good agreement between the low-energy limit of the power-law index for our differential energy spectra and the low-energy photon index of $\Gamma$ observed in Fermi LAT is pointed out and discussed.
Right? Wrong? Outdated?: An evaluation of the controversial Hunter v Moss
Authors: Chung Benny , Chiu Jason Chun Wing 
Published: November 2019

Abstract
Hunter v Moss is a landmark, but also controversial, English trusts law case. In this article, we argue that Hunter v Moss is, indeed, not as controversial or problematic as the academic critics have portrayed it to be, by explaining why those criticisms do not stand. We then argue that the biggest problem with this judgment is its inability to accommodate cases with a financial context, and we propose that the common law courts should rather adopt a facts-based approach.
Using Digital Surveillance Tools for Near Real-Time Mapping of the Risk of International Infectious Disease Spread: Ebola as a Case Study
Authors: Bhatia Sangeeta , Lassmann Britta , Cohn Emily , Carrion Malwina , Kraemer Moritz U. G. , Herringer Mark , Brownstein John , Madoff Larry , Cori Anne , Nouvellet Pierre 
Published: November 2019

AbstractIn our increasingly interconnected world, it is crucial to understand the risk of an outbreak originating in one country or region and spreading to the rest of the world. Digital disease surveillance tools such as ProMED and HealthMap have the potential to serve as important early warning systems as well as complement the field surveillance during an ongoing outbreak. Here we present a flexible statistical model that uses data produced from digital surveillance tools (ProMED and HealthMap) to forecast short term incidence trends in a spatially explicit manner. The model was applied to data collected by ProMED and HealthMap during the 2013-2016 West African Ebola epidemic. The model was able to predict each instance of international spread 1 to 4 weeks in advance. Our study highlights the potential and limitations of using publicly available digital surveillance data for assessing outbreak dynamics in real-time.
Using Mobile Phones For Computer Aided Detection Of Anomalies On Chest Radiographs: Proof Of Concept
Authors: Mitini-Nkhoma Steven 
Published: November 2019

AbstractMastering the art of interpreting chest radiographs can be a long and daunting process. We trained a neural network to classify photographs of chest radiographs into 6 groups. The trained model is hosted on a webserver. The model receives and processes photographs of chest radiographs taken using mobile phones. The system then informs the user the most probable diagnosis. Such systems could prove useful in low resource settings which do not have enough highly trained medical personnel and cannot afford the new generation of CAD based radiology equipment.
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass-indexes
Authors: Scliar Marilia O , Sant Anna Hanaisa P , Santolalla Meddly L , Leal Thiago P , Araújo Nathalia M , Alvim Isabela , Borda Victor , Magalhães Wagner CS , Gouveia Mateus H , Lyra Ricardo , Machado Moara , Michelin Lucas , Rodrigues Maíra R , Araújo Gilderlanio S , Kehdy Fernanda SG , Zolini Camila , Peixoto Sérgio Viana , Luizon Marcelo , Lobo Francisco , Naslavsky Michel S , Yamamoto Guilherme L , Duarte Yeda A O , Hansen Matthew EB , Norris Shane A , Gilman Robert H , Guio Heinner , Hsing Ann W , Mbulaiteye Sam M , Mensah James , Dutil Julie , Yeager Meredith , Yeboah Edward , Tishkoff Sarah A , Choudhury Ananyo , Ramsay Michele , Passos-Bueno Maria Rita , Zatz Mayana , O’Connor Timothy D , Pereira Alexandre C , Barreto Mauricio L , Lima-Costa Maria Fernanda , Horta Bernardo L , Tarazona-Santos Eduardo 
Published: November 2019

ABSTRACTAdmixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely under-represented in genomic studies. Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of Body Mass Index (BMI) in three population-based cohorts from Northeast (Salvador), Southeast (Bambuí) and South (Pelotas) of the country. We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p= 2.76 e-06). This variant is very rare in Europeans but with frequencies of ~3% in West Africa, and has a strong female-specific effect (95%CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat-mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among morbidly obese women from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five-times the effect size of the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects, and for which we replicated associations in Pelotas. We demonstrate how, after a decade of GWAS mostly performed in European-ancestry populations, non-European and admixed populations are a source of new relevant phenotype-associated genetic variants.
Transneuronal delivery of designer-cytokine enables functional recovery after complete spinal cord injury
Authors: Leibinger Marco , Zeitler Charlotte , Gobrecht Philipp , Andreadaki Anastasia , Fischer Dietmar 
Published: November 2019

AbstractSpinal cord injury (SCI) often causes severe and permanent disabilities. The current study uses a transneuronal approach to stimulate spinal cord regeneration by AAV-hyper-IL-6 (hIL-6) application after injury. While preinjury PTEN knockout in cortical motoneurons fails to improve functional recovery after complete spinal cord crush, a single, postinjury injection of hIL-6 into the sensorimotor cortex markedly promotes axon regeneration in the corticospinal and, remarkably, raphespinal tracts enabling significant locomotion recovery of both hindlimbs. Moreover, transduced cortical motoneurons directly innervate serotonergic neurons in both sides of the raphe nuclei equally, enabling the synaptic release of hIL-6 and the transneuronal stimulation of raphe neurons in the brain stem. Functional recovery depends on the regeneration of serotonergic neurons as their degeneration induced by a toxin abolishes the hIL-6-mediated recovery. Thus, the transneuronal application of highly potent cytokines enables functional regeneration by stimulating neurons in the deep brain stem that are otherwise challenging to access, yet highly relevant for functional recovery after SCI.
Application of long-read sequencing for robust identification of correct alleles in genome edited animals
Authors: McCabe Christopher V. , Codner Gemma F. , Allan Alasdair J. , Caulder Adam , Christou Skevoulla , Loeffler Jorik , Mackenzie Matthew , Malzer Elke , Mianné Joffrey , Pike Fran J. , Hutchison Marie , Stewart Michelle E. , Gates Hilary , Wells Sara , Sanderson Nicholas D. , Teboul Lydia 
Published: November 2019

AbstractRecent developments in CRISPR/Cas9 genome editing tools have facilitated the introduction of more complex alleles, often spanning genetic intervals of several kilobases, directly into the embryo. These techniques often produce mosaic founder animals and the introduction of donor templates, via homologous directed repair, can be erroneous or incomplete. Newly generated alleles must be verified at the sequence level across the targeted locus. Screening for the presence of the desired mutant allele using traditional sequencing methods can be challenging due to the size of the desired edit(s) together with founder mosaicism. In order to help disentangle the genetic complexity of these animals, we tested the application of Oxford Nanopore long read sequencing of the targeted locus. Taking advantage of sequencing the entire length of the segment in each single read, we were able to determine whether the entire intended mutant sequence was present in both mosaic founders and their offspring.
AMELIE 2 speeds up Mendelian diagnosis by matching patient phenotype & genotype to primary literature
Authors: Birgmeier Johannes , Haeussler Maximilian , Deisseroth Cole A. , Steinberg Ethan H. , Jagadeesh Karthik A. , Ratner Alexander J. , Guturu Harendra , Wenger Aaron M. , Diekhans Mark E. , Stenson Peter D. , Cooper David N. , Ré Christopher ,   The Manton Center, Beggs Alan H. , Bernstein Jonathan A. , Bejerano Gill 
Published: November 2019

AbstractThe diagnosis of Mendelian disorders requires labor-intensive literature research. Trained clinicians can spend hours looking for the right publication/s supporting a single gene that best explains a patient’s disease. AMELIE (Automatic Mendelian Literature Evaluation) greatly accelerates this process. AMELIE parses all 29 million PubMed abstracts, downloads and further parses hundreds of thousands of full text articles in search of information supporting the causality and associated phenotypes of any published genetic variant. AMELIE then prioritizes patient candidate variants for their likelihood of explaining any patient’s given set of phenotypes. Diagnosis of singleton patients (without relatives’ exomes) is the most time-consuming scenario. AMELIE ranked the causative gene at the very top in 2/3 of 215 diagnosed singleton Mendelian patients. Evaluating only the top 11 AMELIE scored genes of 127 (median) candidate genes per patient results in rapid diagnosis for 90+% of cases. AMELIE-based evaluation of all cases is 3-19x more efficient than hand-curated database-based approaches. We replicate these results on a cohort of clinical cases from Stanford Children’s Health and the Manton Center for Orphan Disease Research. An analysis web portal with our most recent update, programmatic interface and code will be available at AMELIE.stanford.edu. A pilot run of the web portal has already served many thousands of job submissions from dozens of countries.
Family permutation profiling identifies a dynamic protein domain as functionally tolerant to increased conformational entropy
Authors: Atkinson Joshua T. , Jones Alicia M. , Nanda Vikas , Silberg Jonathan J. 
Published: November 2019

ABSTRACTTo investigate whether adenylate kinase (AK) homologs differ in their functional tolerance to mutational lesions that alter dynamics, we subjected three homologs having a range of thermostabilities to random circular permutation and evaluated where new protein termini were non-disruptive to activity using a cellular selection and deep mutational scanning. Analysis of the positional tolerance to new termini, which increase local conformational entropy by breaking peptide bonds, showed that bonds were either functionally sensitive to cleavage across all three homologs, differentially sensitive, or uniformly tolerant. The mobile AMP binding domain, which displays the highest calculated contact energies (frustration), presented the greatest tolerance to new termini across all AKs. In contrast, retention of function in the lid and core domains was more dependent upon AK melting temperature. Thus, regions of high energetic frustration tolerated increases in conformational entropy in a manner that was less dependent on thermostability than regions of lower frustration. Our results suggest that family permutation profiling identifies primary structure that has been selected by evolution for high frustration that is critical to enzymatic activity. They also illustrate how deep mutational scanning can be applied to protein homologs in parallel to learn how topology and function govern mutational tolerance.
The Subsystem Mechanism of Default Mode Network Underlying Rumination: a Reproducible Neuroimaging Study
Authors: Chen Xiao , Chen Ning-Xuan , Shen Yang-Qian , Li Hui-Xian , Li Le , Lu Bin , Zhu Zhi-Chen , Fan Zhen , Yan Chao-Gan 
Published: November 2019

AbstractRumination is a repetitive self-referential thinking style and posited to be an expression of abnormalities in the default mode network (DMN) in major depressive disorder (MDD). Recent evidences indicate DMN is not a unitary network but can be further divided into 3 functionally heterogenous subsystems. However, the subsystem mechanism through which DMN underlie rumination remain unclear. Here, with a modified continuous state-like paradigm, we induced healthy participants to ruminate or imagine objective scenarios (as a distraction control condition) on 3 different MRI scanners. We compared functional connectivities (FC) and inter-subject correlations (ISC) of the DMN and its 3 subsystems between rumination and distraction states. Results yielded a highly reproducible and dissociated pattern. During rumination, within-DMN FC was generally decreased compared to the distraction state. At the subsystem level, we found increased FC between the core and medial temporal lobe (MTL) subsystem and decreased FC between the core and dorsal medial prefrontal cortex (DMPFC) subsystem and within the MTL subsystem. Furthermore, we found decreased ISC within the MTL subsystem. These results suggest a specific and less synchronous activity pattern of DMN during rumination and shed new light on the association between rumination and DMN substrates regarding MDD.
Functional insights from the GC-poor genomes of two aphid parasitoids,Aphidius erviandLysiphlebus fabarum
Authors: Dennis Alice B. , Ballesteros Gabriel I. , Robin Stéphanie , Schrader Lukas , Bast Jens , Berghöfer Jan , Beukeboom Leo , Belghazi Maya , Bretaudeau Anthony , Büllesbach Jan , Cash Elizabeth , Colinet Dominique , Dumas Zoé , Falabella Patrizia , Gatti Jean-Luc , Geuverink Elzemiek , Gibson Joshua D. , Hertäg Corinne , Hartmann Stefanie , Jacquin-Joly Emmanuelle , Lammers Mark , Lavandero Blas I. , Lindenbaum Ina , Massardier-Galata Lauriane , Meslin Camille , Montagné Nicolas , Pak Nina , Poirié Marylène , Salvia Rosanna , Smith Chris R. , Tagu Denis , Tares Sophie , Vogel Heiko , Schwander Tanja , Simon Jean-Christophe , Figueroa Christian C. , Vorburger Christoph , Legeai Fabrice , Gadau Jürgen 
Published: November 2019

AbstractBackgroundParasitoid wasps have fascinating life cycles and play an important role in trophic networks, yet little is known about their genome content and function. Parasitoids that infect aphids are an important group with the potential for biocontrol, and infecting aphids requires overcoming both aphid defenses and their defensive endosymbionts.ResultsWe present thede novogenome assemblies, detailed annotation, and comparative analysis of two closely related parasitoid wasps that target pest aphids:Aphidius erviandLysiphlebus fabarum(Hymenoptera: Braconidae: Aphidiinae). The genomes are small (139 and 141 Mbp), highly syntenic, and the most AT-rich reported thus far for any arthropod (GC content: 25.8% and 23.8%). This nucleotide bias is accompanied by skewed codon usage, and is stronger in genes with adult-biased expression. AT-richness may be the consequence of reduced genome size, a near absence of DNA methylation, and age-specific energy demands. We identify expansions of F-box/Leucine-rich-repeat proteins, suggesting that diversification in this gene family may be associated with their broad host range or with countering defenses from aphids’ endosymbionts. The absence of some immune genes (Toll and Imd pathways) resembles similar losses in their aphid hosts, highlighting the potential impact of symbiosis on both aphids and their parasitoids.ConclusionsThese findings are of fundamental interest for insect evolution and beyond. This will provide a strong foundation for further functional studies including coevolution with respect to their hosts, the basis of successful infection, and biocontrol. Both genomes are available athttps://bipaa.genouest.org.
Cell volume homeostatically controls the rDNA repeat copy number and rRNA synthesis rate in yeast
Authors: Pérez-Ortín José E. , Mena Adriana , Barba-Aliaga Marina , Alonso-Monge Rebeca , Singh Abhyudai , Chávez Sebastián , García-Martínez José 
Published: November 2019

AbstractThe adjustment of transcription and translation rates to variable needs is of utmost importance for the fitness and survival of living cells. We have previously shown that the global transcription rate for RNA polymerase II is regulated differently in cells presenting symmetrical or asymmetrical cell division. The budding yeast Saccharomyces cerevisiae adopts a particular strategy to avoid that the smaller daughter cells increase their total mRNA concentration with every generation. The global mRNA synthesis rate lowers with a growing cell volume, but global mRNA stability increases. In this paper, we address what the solution is to the same theoretical problem for the RNA polymerase I synthesis rate. We find that the RNA polymerase I synthesis rate strictly depends on the copy number of its 35S rRNA gene. For cells with larger cell sizes, such as a mutant cln3 strain, the rDNA repeat copy number is increased by a mechanism based on a feed-back mechanism in which Sir2 histone deacetylase homeostatically controls the amplification of the rRNA genes at the rDNA locus in a volume-dependent manner.
Genomic architecture of artificially and sexually selected traits in a wild cervid
Authors: Anderson S. J. , Côté S. D. , Richard J. H. , Shafer A. B. A. 
Published: November 2019

AbstractCharacterization of the genomic architecture of fitness-related traits such as body size and male ornamentation in mammals provides tools for conservation and management: as both indicators of quality and health, these traits are often subject to sexual and artificial selective pressures. Here we performed high-depth whole genome re-sequencing on pools of individuals representing the phenotypic extremes in our study system for antler and body size in white-tailed deer (Odocoileus virginianus). Samples were selected from a tissue repository containing phenotypic data for 4,466 male white-tailed deer from Anticosti Island, Quebec, with four pools representing the extreme phenotypes for antler and body size in the population, after controlling for age. Our results revealed a largely panmictic population, but detected highly diverged windows between pools for both traits with high shifts in allele frequency (mean allele frequency difference of 14% for and 13% for antler and body SNPs in outlier windows). These regions often contained putative genes of small-to-moderate effect consistent with a polygenic model of quantitative traits. Genes in outlier antler windows had known direct or indirect effects on growth and pathogen defence, while body genes, overall GO terms, and transposable element analyses were more varied and nuanced. Through qPCR analysis we validated both a body and antler gene. Overall, this study revealed the polygenic nature of both antler morphology and body size in free-ranging white-tailed deer and identified target loci for additional analyses.