bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of a dual AGN at z ≃ 3.3 with 20 kpc separation
Authors: Husemann B. , Worseck G. , Arrigoni Battaia F. , Shanks T. 
Published: January 2018

A prediction of the current paradigm of the hierarchical assembly of galaxies is the presence of supermassive dual black holes at separations of a few kpc or less. In this context, we report the detection of a narrow-line emitter within the extended Lyα nebula (~120 kpc diameter) of the luminous radio-quiet quasi-stellar object (QSO) LBQS 0302–0019 at z = 3.286. We identify several high-ionization narrow emission lines (He II, C IV, C III) associated with this point-like source, which we have named “Jil”, which is only ~20 kpc (2.̋9) away from the QSO in projection. Emission-line diagnostics confirm that the source is likely powered by photoionization of an obscured active galactic nucleus (AGN) three orders of magnitude fainter than the QSO. The system represents the tightest unobscured/obscured dual AGN currently known at z > 3, highlighting the power of MUSE to detect these elusive systems.
Applicability of the lattice Boltzmann method to determine the ohmic resistance in equivalent resistor connections
Authors: Espinoza-Andaluz Mayken , Barzola Julio , Guarochico-Moreira Víctor H. , Andersson Martin 
Published: January 2018

Abstract
Knowing the ohmic resistance in the materials allow to know in advance its electrical behavior when a potential difference is applied, and therefore the prediction of the electrical performance can be achieved in a most certain manner. Although the Lattice Boltzmann method (LBM) has been applied to solve several physical phenomena in complex geometries, it has only been used to describe the fluid phase, but applicability studies of LBM on the solid-electric-conducting material have not been carried out yet. The purpose of this paper is to demonstrate the accuracy of calculating the equivalent resistor connections using LBM. Several series and parallel resistor connections are effected. All the computations are carried out with 3D models, and the domain materials are designed by the authors.
Interleukin 1α (IL-1α) Promotes Pathogenic Immature Myeloid Cells and IL-1β Favors Protective Mature Myeloid Cells During Acute Lung Infection
Authors: Periasamy Sivakumar , Harton Jonathan A 
Published: January 2018

Abstract
Bacterial pneumonia is a common risk factor for acute lung injury and sepsis-mediated death, but the mechanisms underlying the overt inflammation and accompanying pathology are unclear. Infiltration of immature myeloid cells and necrotizing inflammation mediate severe pathology and death during pulmonary infection with Francisella tularensis. However, eliciting mature myeloid cells provides protection. Yet, the host factors responsible for this pathologic immature myeloid cell response are unknown. Here, we report that while the influx of both mature and immature myeloid cells is strictly MyD88 dependent, the interleukin 1 (IL-1) receptor mediates an important dual function via its ligands IL-1α and IL-1β. Although IL-1β favors the appearance of bacteria-clearing mature myeloid cells, IL-1α contributes to lung infiltration by ineffective and pathologic immature myeloid cells. Finally, IL-1α and IL-1β are not the sole factors involved, but myeloid cell responses during acute pneumonia were largely unaffected by lung levels of interleukin 10, interleukin 17, CXCL1, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor.
Effects of Celecoxib and Low-dose Aspirin on Outcomes in Adjuvant Aromatase Inhibitor–Treated Patients: CCTG MA.27
Authors: Strasser-Weippl Kathrin , Higgins Michaela J , Chapman Judith-Anne W , Ingle James N , Sledge George W , Budd George T , Ellis Matthew J , Pritchard Kathleen I , Clemons Mark J , Badovinac-Crnjevic Tanja , Han Lei , Gelmon Karen A , Rabaglio Manuela , Elliott Catherine , Shepherd Lois E , Goss Paul E 
Published: January 2018

Abstract

Background
Celecoxib and low-dose aspirin might decrease risk of breast cancer recurrence.

Methods
In the Canadian Cancer Trials Group MA.27, postmenopausal hormone receptor–positive breast cancer patients were randomly assigned (2 × 2) to adjuvant exemestane or anastrozole, and celecoxib or placebo. Low-dose aspirin of 81 mg or less was a stratification factor. Due to concerns about cardiac toxicity, celecoxib use was stopped in December 2004, while stratification by aspirin use was removed through protocol amendment. We examined the effects of celecoxib and low-dose aspirin on event-free survival (EFS), defined as time from random assignment to time of locoregional or distant disease recurrence, new primary breast cancer, or death from any cause; distant disease–free survival (DDFS); and overall survival (OS). All statistical tests were two-sided.

Results
Random assignment to celecoxib (n = 811, 50.0%) or placebo (n = 811, 50.0%) was discontinued after 18 months (n = 1622). At a median of 4.1 years’ follow-up, among 1622 patients, 186 (11.5%) patients had an EFS event: 80 (4.9%) had distant relapse, and 125 (7.7%) died from any cause. Celecoxib did not statistically significantly impact EFS, DDFS, or OS in univariate analysis (respectively, P = .92, P = .55, and P = .56) or multivariable analysis (respectively, P = .74, P = .60, and P = .76). Low-dose aspirin use (aspirin users n = 476, 21.5%; non–aspirin users n = 1733, 78.5%) was associated in univariate analyses with worse EFS (hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.12 to 1.96, P = 0.006) and worse OS (HR = 1.87, 95% CI = 1.35 to 2.61, P < .001). After adjusting for baseline characteristics and treatment arm, aspirin use showed no statistical association with EFS (P = .08) and DDFS (P = .82), but was associated with statistically worse OS (HR = 1.67, 95% CI = 1.13 to 2.49, P = .01).

Conclusion
Random assignment to short-term (≤18 months) celecoxib as well as use of low-dose aspirin showed no effect on DDFS and EFS in multivariable analysis. Low-dose aspirin increased “all-cause” mortality, presumably because of higher preexisting cardiovascular risks.
A Reactive Inelasticity Theoretical Framework for modeling Viscoelasticity, Plastic Deformation, and damage in Soft Tissue
Authors: Safa Babak N. , Santare Michael H. , Elliott Dawn M. 
Published: January 2018

AbstractSoft tissues are biopolymeric materials, primarily made of collagen and water. These tissues have non-linear, anisotropic, and inelastic mechanical behaviors that are often categorized into viscoelastic behavior, plastic deformation, and damage. While tissue’s elastic and viscoelastic mechanical properties have been measured for decades, there is no comprehensive theoretical framework for modeling inelastic behaviors of these tissues that is based on their structure. To model the three major inelastic mechanical behaviors of soft tissue we formulated a structurally inspired continuum mechanics framework based on the energy of molecular bonds that break and reform in response to external loading (reactive bonds). In this framework, we employed the theory of internal state variables and kinetics of molecular bonds. The number fraction of bonds, their reference deformation gradient, and damage parameter were used as internal state variables that allowed for consistent modeling of all three of the inelastic behaviors of tissue by using the same sets of constitutive relations. Several numerical examples are provided that address practical problems in tissue mechanics, including the difference between plastic deformation and damage. This model can be used to identify relationships between tissue’s mechanical response to external loading and its biopolymeric structure.
Baculovirus AC102 is a nucleocapsid protein that is crucial for nuclear actin polymerization and nucleocapsid morphogenesis
Authors: Hepp Susan E. , Borgo Gina M. , Ticau Simina , Ohkawa Taro , Welch Matthew D. 
Published: January 2018

ABSTRACTThe baculovirusAutographa californicamultiple nucleopolyhedrovirus (AcMNPV), the type species of alphabaculoviruses, is an enveloped DNA virus that infects lepidopteran insects and is commonly known as a vector for protein expression and cell transduction. AcMNPV belongs to a diverse group of viral and bacterial pathogens that target the host cell actin cytoskeleton during infection. AcMNPV is unusual, however, in that it absolutely requires actin translocation into the nucleus early in infection, and actin polymerization within the nucleus late in infection coincident with viral replication. Of the six viral factors that are sufficient, when coexpressed, to induce the nuclear localization of actin, only AC102 is essential for viral replication and the nuclear accumulation of actin. We therefore sought to better understand the role of AC102 in actin mobilization in the nucleus early and late in infection. Although AC102 was thought to function early in infection, we found that AC102 is predominantly expressed as a late protein. In addition, we observed that AC102 is required for F-actin assembly in the nucleus during late infection, as well as for proper formation of viral replication structures and nucleocapsid morphogenesis. Finally, we found that AC102 is a nucleocapsid protein and a newly recognized member of a complex consisting of the viral proteins EC27, C42, and the actin polymerization protein P78/83. Taken together, our findings suggest that AC102 is necessary for nucleocapsid morphogenesis and actin assembly during late infection through its role as a component of the P78/83-C42-EC27-AC102 protein complex.IMPORTANCEThe baculovirusAutographa californicamultiple nucleopolyhedrovirus (AcMNPV) is an important biotechnological tool for protein expression and cell transduction, and related nucleopolyhedroviruses are also employed as environmentally benign insecticides. One impact of our work is to better understand the fundamental mechanisms through which AcMNPV exploits the cellular machinery of the host for replication, which may aid in the development of improved baculovirus-based research and industrial tools. Moreover, AcMNPV’s ability to mobilize the host actin cytoskeleton within the cell’s nucleus during infection makes it a powerful cell biological tool. It is becoming increasingly clear that actin plays important roles in the cell’s nucleus, yet the regulation and function of nuclear actin is poorly understood. Our work to better understand how AcMNPV relocalizes and polymerizes actin within the nucleus may reveal fundamental mechanisms that govern nuclear actin regulation and function, even in the absence of viral infection.
Criteria for evaluating molecular markers: Comprehensive quality metrics to improve marker-assisted selection
Authors: Platten John Damien , Cobb Joshua N. , Zantua Rochelle E. 
Published: January 2018

AbstractDespite strong interest over many years, the usage of quantitative trait loci in plant breeding has often failed to live up to expectations. A key weak point in the utilisation of QTLs is the “quality” of markers used during marker-assisted selection (MAS): unreliable markers result in variable outcomes, leading to a perception that MAS products fail to achieve reliable improvement. Most reports of markers used for MAS focus on markers derived from the mapping population. There are very few studies that examine the reliability of these markers in other genetic backgrounds, and critically, no metrics exist to describe and quantify this reliability. To improve the MAS process, this work proposes five core metrics that fully describe the reliability of a marker. These metrics give a comprehensive and quantitative measure of the ability of a marker to correctly classify germplasm as QTL[+]/[-], particularly against a background of high allelic diversity. Markers that score well on these metrics will have far higher reliability in breeding, and deficiencies in specific metrics give information on circumstances under which a marker may not be reliable. The metrics are applicable across different marker types and platforms, allowing an objective comparison of the performance of different markers irrespective of the platform. Evaluating markers using these metrics demonstrates that trait-specific markers consistently out-perform markers designed for other purposes. These metrics also provide a superb set of criteria for designing superior marker systems for a target QTL, enabling the selection of an optimal marker set before committing to design.
BDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior
Authors: Maynard Kristen R. , Hobbs John W. , Phan Badoi N. , Gupta Amolika , Rajpurohit Sumita , Williams Courtney , Rajpurohit Nina , Shin Joo Heon , Jaffe Andrew E. , Martinowich Keri 
Published: January 2018

AbstractBrain-derived neurotrophic factor (Bdnf) transcription is controlled by several promoters, which drive expression of multiple transcripts encoding an identical protein. We previously reported that BDNF derived from promoters I and II is highly expressed in hypothalamus and is critical for regulating aggression in male mice. Here we report that BDNF loss from these promoters causes reduced sexual receptivity and impaired maternal care in female mice, which is concomitant with decreased oxytocin (Oxt) expression during development. We identify a novel link between BDNF signaling, oxytocin, and maternal behavior by demonstrating that ablation of TrkB selectively in OXT neurons partially recapitulates maternal care impairments observed in BDNF-deficient females. Using translating ribosome affinity purification and RNA-sequencing we define a molecular profile for OXT neurons and delineate how BDNF signaling impacts gene pathways critical for structural and functional plasticity. Our findings highlight BDNF as a modulator of sexually-dimorphic hypothalamic circuits that govern female-typical behaviors.
The genome-wide rate and spectrum of spontaneous mutations differs between haploid and diploid yeast
Authors: Sharp Nathaniel P. , Sandell Linnea , James Christopher G. , Otto Sarah P. 
Published: January 2018

AbstractBy altering the dynamics of DNA replication and repair, alternative ploidy states may experience different rates and types of new mutations, leading to divergent evolutionary outcomes. We report the first direct comparison of the genome-wide spectrum of spontaneous mutations arising in haploid and diploid forms of the budding yeast. Characterizing the number, types, locations, and effects of thousands of mutations revealed that haploids were more prone to single-nucleotide and mitochondrial mutations, while larger structural changes were more common in diploids. Mutations were more likely to be detrimental in diploids, even after accounting for the large impact of structural changes, contrary to the prediction that diploidy masks the effects of recessive alleles. Haploidy is expected to reduce the opportunity for conservative DNA repair involving homologous chromosomes, increasing the insertion-deletion rate, but we found little support for this idea. Instead, haploids were more susceptible to particular single-nucleotide mutations in late-replicating genomic regions, resulting in a ploidy difference in the spectrum of substitutions. In diploids we detect mutation rate variation among chromosomes in association with centromere location, a finding that is supported by published polymorphism data. Diploids areSaccharomyces cerevisiaenot simply doubled haploids; instead, our results predict that the spectrum of spontaneous mutations will substantially shape the dynamics of genome evolution in haploid and diploid populations.
Single Cell Molecular Alterations Reveal Pathogenesis and Targets of Concussive Brain Injury
Authors: Arneson Douglas , Zhuang Yumei , Byun Hyae Ran , Ahn In Sook , Ying Zhe , Zhang Guanglin , Gomez-Pinilla Fernando , Yang Xia 
Published: January 2018

ABSTRACTThe complex neuropathology of traumatic brain injury (TBI) is difficult to dissect in the hippocampus considering the convoluted hippocampal cytoarchitecture. As a major casualty of TBI, hippocampal dysfunction results in cognitive decline that may escalate to other neurological disorders, and the molecular basis is hidden in the genomic programs of individual hippocampal cells. Using the unbiased single cell sequencing method Drop-seq, we uncovered the hippocampal cell types most sensitive to concussive mild TBI (mTBI) as well as the vulnerable genes, pathways and cell-cell interactions predictive of disease pathogenesis in a cell-type specific manner, revealing hidden pathogenic mechanisms and potential targets. Targeting Ttr, encoding the thyroid hormone T4 transporter transthyretin, mitigated the genomic and behavioral abnormalities associated with mTBI. Single cell genomics provides unique evidence about altered circuits and pathogenic pathways, and pinpoints new targets amenable to therapeutics in mTBI and related disorders.
Charting the cross-functional map between transcription factors and cancer metabolism
Authors: Ortmayr Karin , Dubuis Sébastien , Zampieri Mattia 
Published: January 2018

AbstractTranscriptional reprogramming of cellular metabolism is a hallmark feature of cancer. However, a systematic approach to study the role of transcription factors (TFs) in mediating cancer metabolic rewiring is missing. Here, we chart a genome-scale map of TF-metabolite associations in human using a new combined computational-experimental framework for large-scale metabolic profiling of adherent cell lines, and the integration of newly generated intracellular metabolic profiles of 54 cancer cell lines with transcriptomic and proteomic data. We unravel a large space of dependencies between TFs and central metabolic pathways, suggesting that the regulation of carbon metabolism in tumors may be more diverse and flexible than previously appreciated. This map provides an unprecedented resource to predict TFs responsible for metabolic transformation in patient-derived tumor samples, opening new opportunities in designing modulators of oncogenic TFs and in understanding disease etiology.
Evaluating Cell Identity from Transcription Profiles
Authors: Mah Nancy , Taškova Katerina , El Amrani Khadija , Hariharan Krithika , Kurtz Andreas , Andrade-Navarro Miguel A. 
Published: January 2018

SummaryInduced pluripotent stem cells (iPS) and direct lineage programming offer promising autologous and patient-specific sources of cells for personalized drug-testing and cell-based therapy. Before these engineered cells can be widely used, it is important to evaluate how well the engineered cell types resemble their intended target cell types. We have developed a method to generate CellScore, a cell identity score that can be used to evaluate the success of an engineered cell type in relation to both its initial and desired target cell type, which are used as references. Of 20 cell transitions tested, the most successful transitions were the iPS cells (CellScore > 0.9), while other transitions (e.g. induced hepatocytes or motor neurons) indicated incomplete transitions (CellScore < 0.5). In principle, the method can be applied to any engineered cell undergoing a cell transition, where transcription profiles are available for the reference cell types and the engineered cell type.HighlightsA curated standard dataset of transcription profiles from normal cell types was created.CellScore evaluates the cell identity of engineered cell types, using the curated dataset.CellScore considers the initial and desired target cell type.CellScore identifies the most successfully engineered clones for further functional testing.
Predicting E. coli concentrations using limited qPCR deployments at Chicago beaches
Authors: Lucius Nick , Rose Kevin , Osborn Callin , Sweeney Matt E , Chesak Renel , Little Daniel Y. , Beslow Scott , Schenk Tom 
Published: January 2018

AbstractCulture-based methods to measure Escherichia coli (E. coli) are used by beach administrators to inform whether bacteria levels represent an elevated risk to swimmers. Since results take up to 12 hours, statistical models are used to forecast bacteria levels in lieu of test results; however they underestimate days with elevated fecal indicator bacteria levels. Quantitative polymerase chain reaction (qPCR) tests return results within 3 hours but are 2 to 5 times more expensive than culture-based methods. This paper presents a prediction model which uses limited deployments of qPCR tested sites with inter-beach correlation to predict when bacteria will exceed acceptable thresholds. The model can be used to inform management decisions on when to warn residents or close beaches due to exposure to the bacteria. Using data from Chicago collected between 2006 and 2016, the model proposed in this paper increased sensitivity from 3.4 percent to 11.2 percent–a 230 percent increase. We find that the correlation between beaches are substantial enough to provide higher levels of precision and sensitivity to predictive models. Thus, limited deployments of qPCR testing can be used to deliver better predictions for beach administrators at lower cost and less complexity.
CITGeneDB: A comprehensive database of human and mouse genes enhancing or suppressing cold-induced thermogenesis validated by perturbation experiments in mice
Authors: Li Jin , Deng Su-Ping , Wei Gang , Yu Peng 
Published: January 2018

AbstractCold-induced thermogenesis increases energy expenditure and can reduce body weight in mammals, so the genes involved in it are thought to be potential therapeutic targets for treating obesity and diabetes. In the quest for more effective therapies, a great deal of research has been conducted to elucidate the regulatory mechanism of cold-induced thermogenesis. Over the last decade, a large number of genes that can enhance or suppress cold-induced thermogenesis have been discovered, but a comprehensive list of these genes is lacking. To fill this gap, we examined all of the annotated human and mouse genes and curated those demonstrated to enhance or suppress cold-induced thermogenesis by in vivo or ex vivo experiments in mice. The results of this highly accurate and comprehensive annotation are hosted on a database called CITGeneDB, which includes a searchable web interface to facilitate broad public use. The database will be updated as new genes are found to enhance or suppress cold-induced thermogenesis. It is expected that CITGeneDB will be a valuable resource in future explorations of the molecular mechanism of cold-induced thermogenesis, helping pave the way for new obesity and diabetes treatments. Database URL: http://citgenedb.yubiolab.org