bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tidal Response of Mars Constrained From Laboratory‐Based Viscoelastic Dissipation Models and Geophysical Data
Authors: Bagheri A. , Khan A. , Al‐Attar D. , Crawford O. , Giardini D. 
Published: August 2019

AbstractWe employ laboratory‐based grain size‐ and temperature‐sensitive rheological models to describe the viscoelastic behavior and tidal response of terrestrial bodies with focus on Mars. We consider five rheological models: Maxwell, extended Burgers, Andrade, Sundberg‐Cooper, and a power law approximation. The question of which model provides the most appropriate description of dissipation in planetary bodies, remains an open issue. To examine this, we build crust and mantle models of Mars (density and elasticity) that are computed self‐consistently through phase equilibrium calculations as a function of pressure, temperature, and bulk composition, whereas core properties are based on an Fe‐S parameterization. We assess the compatibility of the viscoelastic models by inverting tidal response, mean density, and moment of inertia of Mars for its thermal, elastic, and attenuation structure. Our results show that although all viscoelastic models fit the data, (1) their predictions of the tidal response at other periods and harmonic degrees are distinct, implying that our approach can be used to distinguish between the various models from seismic and/or tidal observations (e.g., with InSight), and (2) Maxwell is only capable of fitting data for unrealistically low viscosities. All viscoelastic models converge upon similar interior structure models: large liquid cores (1,750–1,890 km in radius) that contain 17–20.5 wt% S and, consequently, no silicate perovskite‐dominated lower mantle. Finally, the methodology proposed here is generally formulated and applicable to other solar and extrasolar system bodies where the study of tidal dissipation presents an important means for determining interior structure.
Emergence of Summertime Hypoxia and Concurrent Carbonate Mineral Suppression in the Central Bohai Sea, China
Authors: Zhai Wei‐dong , Zhao Hua‐de , Su Ji‐lan , Liu Peng‐fei , Li Yan‐wei , Zheng Nan 
Published: August 2019

AbstractThe Bohai Sea to the west of the North Yellow Sea in the Northwest Pacific is a semienclosed shallow‐water marginal sea on a critical path of eutrophication and environmental degradation. To better understand the Bohai Sea metabolism‐induced summertime dissolved oxygen (DO) decline and acidification, eight field surveys were conducted between August 2011 and September 2017, investigating seasonal and interannual variations in DO and carbonate system parameters in the central Bohai Sea. The historically lowest Bohai Sea DO was recorded at 66 μmol O2/kg in subsurface waters in early September 2015. By comparing our data set with literature data obtained in the 1980s, 1990s, and 2000s, the emergence history of summertime hypoxia in this marginal sea was shown. Associated with the seasonal DO shortage, the metabolism‐enhanced CO2 accumulation in subsurface waters in summer resulted in critical aragonite saturation states of close to or even less than 1.5, threatening calcifiers with potentially severe consequences for valuable shellfish fisheries. Based on model results combining the aerobic respiration (as indicated by apparent oxygen utilization) and the given wintertime/springtime atmospheric CO2 level of the time, this study suggests that combined stresses of the seasonal DO shortage and CO2 acidification capable of threatening Bohai Sea ecosystems could develop within decades.
Microparticles from tumors exposed to radiation promote immune evasion in part by PD-L1
Authors: Timaner Michael , Kotsofruk Ruslana , Raviv Ziv , Magidey Ksenia , Shechter Dvir , Kan Tal , Nevelsky Alexander , Daniel Shahar , de Vries Elisabeth G. E. , Zhang Tongwu , Kaidar-Person Orit , Kerbel Robert S. , Shaked Yuval 
Published: August 2019

AbstractRadiotherapy induces immune-related responses in cancer patients by various mechanisms. Here, we investigate the immunomodulatory role of tumor-derived microparticles (TMPs)—extracellular vesicles shed from tumor cells—following radiotherapy. We demonstrate that breast carcinoma cells exposed to radiation shed TMPs containing elevated levels of immune-modulating proteins, one of which is programmed death-ligand 1 (PD-L1). These TMPs inhibit cytotoxic T lymphocyte (CTL) activity both in vitro and in vivo, and thus promote tumor growth. Evidently, adoptive transfer of CTLs pre-cultured with TMPs from irradiated breast carcinoma cells increases tumor growth rates in mice recipients in comparison with control mice receiving CTLs pre-cultured with TMPs from untreated tumor cells. In addition, blocking the PD-1-PD-L1 axis, either genetically or pharmacologically, partially alleviates TMP-mediated inhibition of CTL activity, suggesting that the immunomodulatory effects of TMPs in response to radiotherapy is mediated, in part, by PD-L1. Overall, our findings provide mechanistic insights into the tumor immune surveillance state in response to radiotherapy and suggest a therapeutic synergy between radiotherapy and immune checkpoint inhibitors.
Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination
Authors: Kirby Leslie , Jin Jing , Cardona Jaime Gonzalez , Smith Matthew D. , Martin Kyle A. , Wang Jingya , Strasburger Hayley , Herbst Leyla , Alexis Maya , Karnell Jodi , Davidson Todd , Dutta Ranjan , Goverman Joan , Bergles Dwight , Calabresi Peter A. 
Published: August 2019

AbstractOligodendrocyte precursor cells (OPCs) are abundant in the adult central nervous system, and have the capacity to regenerate oligodendrocytes and myelin. However, in inflammatory diseases such as multiple sclerosis (MS) remyelination is often incomplete. To investigate how neuroinflammation influences OPCs, we perform in vivo fate-tracing in an inflammatory demyelinating mouse model. Here we report that OPC differentiation is inhibited by both effector T cells and IFNγ overexpression by astrocytes. IFNγ also reduces the absolute number of OPCs and alters remaining OPCs by inducing the immunoproteasome and MHC class I. In vitro, OPCs exposed to IFNγ cross-present antigen to cytotoxic CD8 T cells, resulting in OPC death. In human demyelinated MS brain lesions, but not normal appearing white matter, oligodendroglia exhibit enhanced expression of the immunoproteasome subunit PSMB8. Therefore, OPCs may be co-opted by the immune system in MS to perpetuate the autoimmune response, suggesting that inhibiting immune activation of OPCs may facilitate remyelination.
Viral priming of cell intrinsic innate antiviral signaling by the unfolded protein response
Authors: Carletti Tea , Zakaria Mohammad Khalid , Faoro Valentina , Reale Laura , Kazungu Yvette , Licastro Danilo , Marcello Alessandro 
Published: August 2019

AbstractThe innate response to a pathogen is critical in determining the outcome of the infection. However, the interplay of different cellular responses that are activated following viral infection and their contribution to innate antiviral signalling has not been clearly established. This work shows that flaviviruses, including Dengue, Zika, West Nile and Tick-borne encephalitis viruses, activate the unfolded protein response before transcription of interferon regulatory factor 3 induced genes. Infection in conditions of unfolded protein response priming leads to early activation of innate antiviral responses and cell intrinsic inhibition of viral replication, which is interferon regulatory factor 3 dependent. These results demonstrate that the unfolded protein response is not only a physiological reaction of the cell to viral infection, but also synergizes with pattern recognition sensing to mount a potent antiviral response.
A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination
Authors: Li Ran , Bitoun Emmanuelle , Altemose Nicolas , Davies Robert W. , Davies Benjamin , Myers Simon R. 
Published: August 2019

AbstractDuring meiotic recombination, homologue-templated repair of programmed DNA double-strand breaks (DSBs) produces relatively few crossovers and many difficult-to-detect non-crossovers. By intercrossing two diverged mouse subspecies over five generations and deep-sequencing 119 offspring, we detect thousands of crossover and non-crossover events genome-wide with unprecedented power and spatial resolution. We find that both crossovers and non-crossovers are strongly depleted at DSB hotspots where the DSB-positioning protein PRDM9 fails to bind to the unbroken homologous chromosome, revealing that PRDM9 also functions to promote homologue-templated repair. Our results show that complex non-crossovers are much rarer in mice than humans, consistent with complex events arising from accumulated non-programmed DNA damage. Unexpectedly, we also find that GC-biased gene conversion is restricted to non-crossover tracts containing only one mismatch. These results demonstrate that local genetic diversity profoundly alters meiotic repair pathway decisions via at least two distinct mechanisms, impacting genome evolution and Prdm9-related hybrid infertility.
Atomic structure of the Epstein-Barr virus portal
Authors: Machón Cristina , Fàbrega-Ferrer Montserrat , Zhou Daming , Cuervo Ana , Carrascosa José L. , Stuart David I. , Coll Miquel 
Published: August 2019

AbstractHerpesviridae is a vast family of enveloped DNA viruses that includes eight distinct human pathogens, responsible for diseases that range from almost asymptomatic to severe and life-threatening. Epstein-Barr virus infects B-cells and epithelial cells, causing infectious mononucleosis, as well as a number of cancers. Epstein-Barr infection cannot be cured since neither vaccine nor antiviral drug treatments are available. All herpesviruses contain a linear double-stranded DNA genome, enclosed within an icosahedral capsid. Viral portal protein plays a key role in the procapsid assembly and DNA packaging. The portal is the entrance and exit pore for the viral genome, making it an attractive pharmacological target for the development of new antivirals. Here we present the atomic structure of the portal protein of Epstein-Barr virus, solved by cryo-electron microscopy at 3.5 Å resolution. The detailed architecture of this protein suggests that it plays a functional role in DNA retention during packaging.
Changes in gene expression predictably shift and switch genetic interactions
Authors: Li Xianghua , Lalić Jasna , Baeza-Centurion Pablo , Dhar Riddhiman , Lehner Ben 
Published: August 2019

AbstractNon-additive interactions between mutations occur extensively and also change across conditions, making genetic prediction a difficult challenge. To better understand the plasticity of genetic interactions (epistasis), we combine mutations in a single protein performing a single function (a transcriptional repressor inhibiting a target gene). Even in this minimal system, genetic interactions switch from positive (suppressive) to negative (enhancing) as the expression of the gene changes. These seemingly complicated changes can be predicted using a mathematical model that propagates the effects of mutations on protein folding to the cellular phenotype. More generally, changes in gene expression should be expected to alter the effects of mutations and how they interact whenever the relationship between expression and a phenotype is nonlinear, which is the case for most genes. These results have important implications for understanding genotype-phenotype maps and illustrate how changes in genetic interactions can often—but not always—be predicted by hierarchical mechanistic models.
Field theory for recurrent mobility
Authors: Mazzoli Mattia , Molas Alex , Bassolas Aleix , Lenormand Maxime , Colet Pere , Ramasco José J. 
Published: August 2019

AbstractUnderstanding human mobility is crucial for applications such as forecasting epidemic spreading, planning transport infrastructure and urbanism in general. While, traditionally, mobility information has been collected via surveys, the pervasive adoption of mobile technologies has brought a wealth of (real time) data. The easy access to this information opens the door to study theoretical questions so far unexplored. In this work, we show for a series of worldwide cities that commuting daily flows can be mapped into a well behaved vector field, fulfilling the divergence theorem and which is, besides, irrotational. This property allows us to define a potential for the field that can become a major instrument to determine separate mobility basins and discern contiguous urban areas. We also show that empirical fluxes and potentials can be well reproduced and analytically characterized using the so-called gravity model, while other models based on intervening opportunities have serious difficulties.
Identification of somatic mutations in single cell DNA-seq using a spatial model of allelic imbalance
Authors: Luquette Lovelace J. , Bohrson Craig L. , Sherman Max A. , Park Peter J. 
Published: August 2019

AbstractRecent advances in single cell technology have enabled dissection of cellular heterogeneity in great detail. However, analysis of single cell DNA sequencing data remains challenging due to bias and artifacts that arise during DNA extraction and whole-genome amplification, including allelic imbalance and dropout. Here, we present a framework for statistical estimation of allele-specific amplification imbalance at any given position in single cell whole-genome sequencing data by utilizing the allele frequencies of heterozygous single nucleotide polymorphisms in the neighborhood. The resulting allelic imbalance profile is critical for determining whether the variant allele fraction of an observed mutation is consistent with the expected fraction for a true variant. This method, implemented in SCAN-SNV (Single Cell ANalysis of SNVs), substantially improves the identification of somatic variants in single cells. Our allele balance framework is broadly applicable to genotype analysis of any variant type in any data that might exhibit allelic imbalance.
NK cells are activated and primed for skin-homing during acute dengue virus infection in humans
Authors: Zimmer Christine L. , Cornillet Martin , Solà-Riera Carles , Cheung Ka-Wai , Ivarsson Martin A. , Lim Mei Qiu , Marquardt Nicole , Leo Yee-Sin , Lye David Chien , Klingström Jonas , MacAry Paul A. , Ljunggren Hans-Gustaf , Rivino Laura , Björkström Niklas K. 
Published: August 2019

AbstractDespite animal models showing that natural killer (NK) cells are important players in the early defense against many viral infections, the NK cell response is poorly understood in humans. Here we analyze the phenotype, temporal dynamics, regulation and trafficking of NK cells in a patient cohort with acute dengue virus infection. NK cells are robustly activated and proliferate during the first week after symptom debut. Increased IL-18 levels in plasma and in induced skin blisters of DENV-infected patients, as well as concomitant signaling downstream of the IL-18R, suggests an IL-18-dependent mechanism in driving the proliferative NK cell response. Responding NK cells have a less mature phenotype and a distinct chemokine-receptor imprint indicative of skin-homing. A corresponding NK cell subset can be localized to skin early during acute infection. These data provide evidence of an IL-18-driven NK cell proliferation and priming for skin-homing during an acute viral infection in humans.
GSNOR provides plant tolerance to iron toxicity via preventing iron-dependent nitrosative and oxidative cytotoxicity
Authors: Li Baohai , Sun Li , Huang Jianyan , Göschl Christian , Shi Weiming , Chory Joanne , Busch Wolfgang 
Published: August 2019

AbstractIron (Fe) is essential for life, but in excess can cause oxidative cytotoxicity through the generation of Fe-catalyzed reactive oxygen species. It is yet unknown which genes and mechanisms can provide Fe-toxicity tolerance. Here, we identify S-nitrosoglutathione-reductase (GSNOR) variants underlying a major quantitative locus for root tolerance to Fe-toxicity in Arabidopsis using genome-wide association studies and allelic complementation. These variants act largely through transcript level regulation. We further show that the elevated nitric oxide is essential for Fe-dependent redox toxicity. GSNOR maintains root meristem activity and prevents cell death via inhibiting Fe-dependent nitrosative and oxidative cytotoxicity. GSNOR is also required for root tolerance to Fe-toxicity throughout higher plants such as legumes and monocots, which exposes an opportunity to address crop production under high-Fe conditions using natural GSNOR variants. Overall, this study shows that genetic or chemical modulation of the nitric oxide pathway can broadly modify Fe-toxicity tolerance.
Conformational heterogeneity in human interphase chromosome organization reconciles the FISH and Hi-C paradox
Authors: Shi Guang , Thirumalai D. 
Published: August 2019

AbstractHi-C experiments are used to infer the contact probabilities between loci separated by varying genome lengths. Contact probability should decrease as the spatial distance between two loci increases. However, studies comparing Hi-C and FISH data show that in some cases the distance between one pair of loci, with larger Hi-C readout, is paradoxically larger compared to another pair with a smaller value of the contact probability. Here, we show that the FISH-Hi-C paradox can be resolved using a theory based on a Generalized Rouse Model for Chromosomes (GRMC). The FISH-Hi-C paradox arises because the cell population is highly heterogeneous, which means that a given contact is present in only a fraction of cells. Insights from the GRMC is used to construct a theory, without any adjustable parameters, to extract the distribution of subpopulations from the FISH data, which quantitatively reproduces the Hi-C data. Our results show that heterogeneity is pervasive in genome organization at all length scales, reflecting large cell-to-cell variations.
Quantitative assessments and clinical outcomes in HER2 equivocal 2018 ASCO/CAP ISH group 4 breast cancer
Authors: Gupta Swati , Neumeister Veronique , McGuire John , Song Yan S. , Acs Balazs , Ho Kenneth , Weidler Jodi , Wong Wendy , Rhees Brian , Bates Michael , Rimm David L. , Bossuyt Veerle 
Published: August 2019

AbstractWe quantified human epidermal growth factor receptor 2 (HER2) RNA and protein expression in 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) in situ hybridization (ISH) group 4 (HER2/centromeric probe 17 (CEP17) ratio <2.0, average HER2 copy number ≥4.0 and <6.0, and 2013 ASCO/CAP ISH equivocal) breast cancers. Breast cancers in 2018 ASCO/CAP ISH group 4 between 2014 and 2017 were identified from the Yale archives. Sixty-three patients (34 with HER2 immunohistochemistry (IHC) 0/1+ and 29 with HER2 IHC 2+) were included. We compared patient characteristics, systemic treatments, and outcomes. We assessed HER2 by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and quantitative immunofluorescence (QIF). Among ISH group 4 cancers, higher HER2 mRNA (P < 0.0001) but similar HER2 protein levels were observed in IHC 2+ compared to IHC 0/1+ cancers. The distribution of RT-qPCR and QIF scores were independent of fluorescence in situ hybridization (FISH) ratio/copy number. Concordance between HER2 RT-qPCR and QIF was 69.8% (r = 0.52). Among 29 patients with IHC2+ results, 16 were HER2 positive by RT-qPCR and 12 were HER2 positive by QIF. Systemic treatment, recurrence, and survival outcomes were comparable among ISH group 4 cancers regardless of IHC 0/1+ or 2+ results. ISH group 4 cancers appear to form a distinct group with intermediate levels of RNA/protein expression, close to positive/negative cut points. Therefore, adjudication into positive or negative categories may not be meaningful. Our results support the 2018 ASCO/CAP recommendation to refrain from routine additional testing of these samples. Additional outcome information after trastuzumab treatment for patients in this special group might help to guide treatment decisions in these patients.
Predicting the dissolution kinetics of silicate glasses by topology-informed machine learning
Authors: Liu Han , Zhang Tony , Anoop Krishnan N. M. , Smedskjaer Morten M. , Ryan Joseph V. , Gin Stéṕhane , Bauchy Mathieu 
Published: August 2019

AbstractMachine learning (ML) regression methods are promising tools to develop models predicting the properties of materials by learning from existing databases. However, although ML models are usually good at interpolating data, they often do not offer reliable extrapolations and can violate the laws of physics. Here, to address the limitations of traditional ML, we introduce a “topology-informed ML” paradigm—wherein some features of the network topology (rather than traditional descriptors) are used as fingerprint for ML models—and apply this method to predict the forward (stage I) dissolution rate of a series of silicate glasses. We demonstrate that relying on a topological description of the atomic network (i) increases the accuracy of the predictions, (ii) enhances the simplicity and interpretability of the predictive models, (iii) reduces the need for large training sets, and (iv) improves the ability of the models to extrapolate predictions far from their training sets. As such, topology-informed ML can overcome the limitations facing traditional ML (e.g., accuracy vs. simplicity tradeoff) and offers a promising route to predict the properties of materials in a robust fashion.
Seasonal and annual changes in PAH concentrations in a remote site in the Pacific Ocean
Authors: Miura Kaori , Shimada Kojiro , Sugiyama Taichi , Sato Kei , Takami Akinori , Chan Chak K. , Kim In Sun , Kim Yong Pyo , Lin Neng-Huei , Hatakeyama Shiro 
Published: August 2019

AbstractThis paper reports the long term observation of particle-associated polycyclic aromatic hydrocarbons (PAHs) at Cape Hedo Atmosphere and Aerosol Monitoring Station, a remote site in the Western Pacific Ocean, from 2008 to 2015. This is the first long-term study that evaluated the contribution of long-range transport of PAHs in East Asia. No obvious trend (P > 0.05) was found in a particular season over the years. However, there are seasonal variations of PAH concentrations with higher in spring and winter. The higher PAH are attributed to air masses from the area including part of China. Source apportionment using three different approaches, i.e., PAH compositional pattern analysis, PAH diagnostic ratio analysis and positive matrix factorization modeling, showed the combined high contribution of biomass burning (18%, 14%) and coal combustion (33%, 24%) in spring and winter. In addition, the contribution of ship emissions (35%) was relatively high in spring, whereas that of vehicle emissions (36%) was relatively high in winter. The contribution of coal combustion to PAH has decreased throughout the years, likely due to changes in energy structure in China. The contribution of biomass burning to PAH has showed no trend, being stable, and that of vehicular emissions has increased.