bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shear‐Parallel Tropical Convective Systems: Importance of Cold Pools and Wind Shear
Authors: Grant Leah D. , Moncrieff Mitchell W. , Lane Todd P. , van den Heever Susan C. 
Published: June 2020

AbstractThe impact of cold pools on line‐orientated convective systems is assessed using idealized simulations of tropical oceanic convection under weak, moderate, and strong wind shear regimes. Cold pools are weakened by suppressing evaporation in the shallow subcloud layer. Analysis of objectively identified convective systems reveals that the convection with weaker cold pools is more often oriented parallel, rather than perpendicular, to the wind shear. The cold pool‐induced orientation changes are most pronounced in the strong shear environment. Interactions between convective orientation and the tropical atmosphere are assessed. Simulations with shear‐parallel convection demonstrate more top‐of‐atmosphere upwelling longwave radiation and less reflected shortwave radiation due to changes in convective anvils, faster‐propagating larger‐scale gravity waves, narrower cross‐shear moisture distributions, and differences in convective momentum fluxes. The results highlight critical interactions across convective scales, mesoscales, and climate scales, as well as avenues for parameterizing structural modes of mesoscale‐organized convection in global models.
Morphodynamic Hierarchy and the Fabric of the Sedimentary Record
Authors: Ganti Vamsi , Hajek Elizabeth A. , Leary Kate , Straub Kyle M. , Paola Chris 
Published: June 2020

AbstractThe low temporal completeness of fluvial strata could indicate that recorded events represent unusual and extreme conditions. However, field observations suggest that preserved strata predominantly record relatively common transport conditions—a paradox termed the strange ordinariness of fluvial strata. We theorize that the self‐organization of fluvial systems into a morphodynamic hierarchy that spans bed to basin scales facilitates the preservation of ordinary events in fluvial strata. Using a new probabilistic model and existing field and experimental data sets across these scales, we show that fluvial morphodynamic hierarchy enhances the stratigraphic preservation of medial topography—ordinary events. We show that lower‐order landforms have a higher likelihood of complete preservation when the kinematic rates of evolution of successive levels in the morphodynamic hierarchy are comparable. We highlight how relative changes in kinematic rates of evolution of successive levels in the morphodynamic hierarchy can manifest as major shifts in stratigraphic architecture through Earth history.
Spatial Dependence of Floods Shaped by Spatiotemporal Variations in Meteorological and Land‐Surface Processes
Authors: Brunner Manuela I. , Gilleland Eric , Wood Andy , Swain Daniel L. , Clark Martyn 
Published: June 2020

AbstractFloods often affect large regions and cause adverse societal impacts. Regional flood hazard and risk assessments therefore require a realistic representation of spatial flood dependencies to avoid the overestimation or underestimation of risk. However, it is not yet well understood how spatial flood dependence, that is, the degree of co‐occurrence of floods at different locations, varies in space and time and which processes influence the strength of this dependence. We identify regions in the United States with seasonally similar flood behavior and analyze processes governing spatial dependence. We find that spatial flood dependence varies regionally and seasonally and is generally strongest in winter and spring and weakest in summer and fall. Moreover, we find that land‐surface processes are crucial in shaping the spatiotemporal characteristics of flood events. We conclude that the regional and seasonal variations in spatial flood dependencies must be considered when conducting current and future flood risk assessments.
Feedback and Ballooning Instabilities in the Magnetosphere‐Ionosphere Coupling
Authors: Watanabe T.‐H. 
Published: June 2020

AbstractA unified model for the feedback and ballooning instabilities in the magnetosphere‐ionosphere (M‐I) coupling is developed by means of the reduced magnetohydrodynamic and two‐fluid equations, involving the local current closure and the ionospheric conductivity change in a scale of auroral fine structures, self‐consistently. In a low pressure gradient case, the Alfvén harmonics are destabilized through the feedback mechanism, while the ballooning instability appears if the magnetospheric pressure gradient exceeds a critical value. Transition of the dominant instability between the feedback and ballooning modes is brought by change of the normalized pressure gradient or the convection electric field in the magnetosphere. The obtained results imply a variety of appearance of auroral arcs and beads in the M‐I coupling system.
Short‐term Impacts of Arctic Summer Cyclones on Sea Ice Extent in the Marginal Ice Zone
Authors: Finocchio Peter M. , Doyle James D. , Stern Daniel P. , Fearon Matthew G. 
Published: June 2020

AbstractThe degree to which Arctic cyclones locally affect sea ice cover during the melt season is unclear. To address this, we use the ERA‐5 reanalysis to statistically analyze how surface energy fluxes and wind forcing from Arctic cyclones in the marginal ice zone between May and August (1999–2018) locally affect sea ice extent on 1–10 day time scales. In May and June, cyclones decelerate the local seasonal loss of sea ice extent compared to when no cyclone is present, which we hypothesize is due to cyclones reducing net shortwave radiative fluxes at the surface. By July and August, cyclones no longer decelerate the seasonal loss of sea ice extent, despite still reducing the net surface energy flux. Surface wind forcing across the ice edge only explains up to 13.5% of the variance in local sea ice extent in August, suggesting that processes other than wind‐induced drift and atmospheric energy fluxes drive late‐summer sea ice extent variability.
Inversion of the Energetic Electron “Zebra Stripe” Pattern Present in the Earth's Inner Belt and Slot Region: First Observations and Interpretation
Authors: Lejosne Solène , Mozer F. S. 
Published: June 2020

AbstractEnergetic electron spectra in the Earth's inner belt and slot region usually display extrema at some energies that form uninterrupted lines when color‐coded in two‐dimensional maps in which one axis represents the normalized equatorial distance, L, and the other axis represents kinetic energy. These patterns are called “zebra stripes.” This letter presents the first observations of zebra stripe inversions: Lines of local minima in the electron spectra at low L values (below L = 2) turn into lines of local maxima in the electron spectra at higher L values, and vice versa. The observations are interpreted by specifying the connection between fluctuations in directional differential fluxes and radial disturbances of trapped population drift motion. The analysis highlights the role of flux energy‐ and radial‐gradients when it comes to determining radial motion from particle data. The underlying method applies to a variety of problems, whether at Earth or at the outer planets.
Charon: A Brief History of Tides
Authors: Rhoden Alyssa Rose , Skjetne Helle L. , Henning Wade G. , Hurford Terry A. , Walsh Kevin J. , Stern S. A. , Olkin C. B. , Spencer J. R. , Weaver H. A. , Young L. A. , Ennico K. ,   and the New Horizons Team
Published: June 2020

AbstractIn 2015, the New Horizons spacecraft flew past Pluto and its moon Charon, providing the first clear look at Charon's surface. New Horizons images revealed an ancient surface, a large, intricate canyon system, and many fractures, among other geologic features. Here, we assess whether tidal stresses played a significant role in the formation of Charon's tensile fractures. Although presently in a circular orbit, most scenarios for Charon's orbital evolution include an eccentric orbit for some period of time and possibly an internal ocean. Past work has shown that these conditions could have generated stresses comparable in magnitude to other tidally fractured moons, such as Europa and Enceladus. However, we find no correlation between observed fracture orientations and those predicted to form due to eccentricity driven tidal stress. It, thus, seems more likely that Charon's orbit circularized before its ocean froze and that either tidal stresses alone were insufficient to fracture the surface or subsequent resurfacing removed these ancient fractures.
The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma
Authors: Crawford Lisa J. , Campbell David C. , Morgan Jonathan J. , Lawson Michelle A. , Down Jennifer M. , Chauhan Dharminder , McAvera Roisin M. , Morris Treen C. , Hamilton Claudia , Krishnan Aswini , Rajalingam Krishnaraj , Chantry Andrew D. , Irvine Alexandra E. 
Published: June 2020

AbstractProteasome inhibitors have provided a significant advance in the treatment of multiple myeloma (MM). Consequently, there is increasing interest in developing strategies to target E3 ligases, de-ubiquitinases, and/or ubiquitin receptors within the ubiquitin proteasome pathway, with an aim to achieve more specificity and reduced side-effects. Previous studies have shown a role for the E3 ligase HUWE1 in modulating c-MYC, an oncogene frequently dysregulated in MM. Here we investigated HUWE1 in MM. We identified elevated expression of HUWE1 in MM compared with normal cells. Small molecule-mediated inhibition of HUWE1 resulted in growth arrest of MM cell lines without significantly effecting the growth of normal bone marrow cells, suggesting a favorable therapeutic index. Studies using a HUWE1 knockdown model showed similar growth inhibition. HUWE1 expression positively correlated with MYC expression in MM bone marrow cells and correspondingly, genetic knockdown and biochemical inhibition of HUWE1 reduced MYC expression in MM cell lines. Proteomic identification of HUWE1 substrates revealed a strong association of HUWE1 with metabolic processes in MM cells. Intracellular glutamine levels are decreased in the absence of HUWE1 and may contribute to MYC degradation. Finally, HUWE1 depletion in combination with lenalidomide resulted in synergistic anti-MM activity in both in vitro and in vivo models. Taken together, our data demonstrate an important role of HUWE1 in MM cell growth and provides preclinical rationale for therapeutic strategies targeting HUWE1 in MM.
First-in-human study of the PARP/tankyrase inhibitor E7449 in patients with advanced solid tumours and evaluation of a novel drug-response predictor
Authors: Plummer Ruth , Dua Divyanshu , Cresti Nicola , Drew Yvette , Stephens Peter , Foegh Marie , Knudsen Steen , Sachdev Pallavi , Mistry Bipin M. , Dixit Vaishali , McGonigle Sharon , Hall Nancy , Matijevic Mark , McGrath Shannon , Sarker Debashis 
Published: June 2020

AbstractBackgroundThis phase 1 study examined the safety, maximum-tolerated dose (MTD) and antitumour activity of E7449, a novel PARP 1/2 and tankyrase 1/2 inhibitor.MethodsE7449 was orally administered once daily in 28-day cycles to patients with advanced solid tumours (50–800-mg doses). Archival tumour samples from consenting patients were evaluated for the expression of 414 genes in a biomarker panel (2X-121 drug-response predictor [DRP]) found to be predictive of the response to E7449 in cell lines.ResultsForty-one patients were enrolled (13 pancreatic, 5 ovarian, 4 each with breast, lung or colorectal cancer and 11 with other tumour types). The most common grade ≥3 treatment-related adverse event was fatigue (n = 7, 17.1%). Five patients experienced a dose-limiting toxicity (fatigue,n = 4, 800 mg; anaphylaxis,n = 1, 600 mg) for an MTD of 600 mg. E7449 exhibited antitumour activity in solid tumours, including 2 partial responses (PRs), and stable disease (SD) in 13 patients, which was durable (>23 weeks) for 8 patients. In 13 patients, the 2X-121 DRP identified those achieving PR and durable SD. E7449 showed good tolerability, promising antitumour activity and significant concentration-dependent PARP inhibition following 50–800-mg oral dosing.ConclusionThe results support further clinical investigation of E7449 and its associated biomarker 2X-121 DRP.Clinical trial registrationwww.ClinicalTrials.gov code: NCT01618136.
Properties of structural variants and short tandem repeats associated with gene expression and complex traits
Authors: Jakubosky David , D’Antonio Matteo , Bonder Marc Jan , Smail Craig , Donovan Margaret K. R. , Young Greenwald William W. , Matsui Hiroko ,   i2QTL Consortium, Bonder Marc J. , Cai Na , Carcamo-Orive Ivan , D’Antonio Matteo , Frazer Kelly A. , Young Greenwald William W. , Jakubosky David , Knowles Joshua W. , Matsui Hiroko , McCarthy Davis J. , Mirauta Bogdan A. , Montgomery Stephen B. , Quertermous Thomas , Seaton Daniel D. , Smail Craig , Smith Erin N. , Stegle Oliver , D’Antonio-Chronowska Agnieszka , Stegle Oliver , Smith Erin N. , Montgomery Stephen B. , DeBoever Christopher , Frazer Kelly A. 
Published: June 2020

AbstractStructural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA variants which vastly differ in their sizes and distributions across the genome. Here, we identify genomic features of SV classes and STRs that are associated with gene expression and complex traits, including their locations relative to eGenes, likelihood of being associated with multiple eGenes, associated eGene types (e.g., coding, noncoding, level of evolutionary constraint), effect sizes, linkage disequilibrium with tagging single nucleotide variants used in GWAS, and likelihood of being associated with GWAS traits. We identify a set of high-impact SVs/STRs associated with the expression of three or more eGenes via chromatin loops and show that they are highly enriched for being associated with GWAS traits. Our study provides insights into the genomic properties of structural variant classes and short tandem repeats that are associated with gene expression and human traits.
Multisecond ligand dissociation dynamics from atomistic simulations
Authors: Wolf Steffen , Lickert Benjamin , Bray Simon , Stock Gerhard 
Published: June 2020

AbstractCoarse-graining of fully atomistic molecular dynamics simulations is a long-standing goal in order to allow the description of processes occurring on biologically relevant timescales. For example, the prediction of pathways, rates and rate-limiting steps in protein-ligand unbinding is crucial for modern drug discovery. To achieve the enhanced sampling, we perform dissipation-corrected targeted molecular dynamics simulations, which yield free energy and friction profiles of molecular processes under consideration. Subsequently, we use these fields to perform temperature-boosted Langevin simulations which account for the desired kinetics occurring on multisecond timescales and beyond. Adopting the dissociation of solvated sodium chloride, trypsin-benzamidine and Hsp90-inhibitor protein-ligand complexes as test problems, we reproduce rates from molecular dynamics simulation and experiments within a factor of 2–20, and dissociation constants within a factor of 1–4. Analysis of friction profiles reveals that binding and unbinding dynamics are mediated by changes of the surrounding hydration shells in all investigated systems.
Hardening in Au-Ag nanoboxes from stacking fault-dislocation interactions
Authors: Patil Radhika P. , Doan David , Aitken Zachary H. , Chen Shuai , Kiani Mehrdad T. , Barr Christopher M. , Hattar Khalid , Zhang Yong-Wei , Gu X. Wendy 
Published: June 2020

AbstractPorous, nano-architected metals with dimensions down to ~10 nm are predicted to have extraordinarily high strength and stiffness per weight, but have been challenging to fabricate and test experimentally. Here, we use colloidal synthesis to make ~140 nm length and ~15 nm wall thickness hollow Au-Ag nanoboxes with smooth and rough surfaces. In situ scanning electron microscope and transmission electron microscope testing of the smooth and rough nanoboxes show them to yield at 130 ± 45 MPa and 96 ± 31 MPa respectively, with significant strain hardening. A higher strain hardening rate is seen in rough nanoboxes than smooth nanoboxes. Finite element modeling is used to show that the structure of the nanoboxes is not responsible for the hardening behavior suggesting that material mechanisms are the source of observed hardening. Molecular dynamics simulations indicate that hardening is a result of interactions between dislocations and the associated increase in dislocation density.
Impaired peroxisomal import in Drosophila oenocytes causes cardiac dysfunction by inducing upd3 as a peroxikine
Authors: Huang Kerui , Miao Ting , Chang Kai , Kim Jinoh , Kang Ping , Jiang Qiuhan , Simmonds Andrew J. , Di Cara Francesca , Bai Hua 
Published: June 2020

AbstractAging is characterized by a chronic, low-grade inflammation, which is a major risk factor for cardiovascular diseases. It remains poorly understood whether pro-inflammatory factors released from non-cardiac tissues contribute to the non-autonomous regulation of age-related cardiac dysfunction. Here, we report that age-dependent induction of cytokine unpaired 3 (upd3) in Drosophila oenocytes (hepatocyte-like cells) is the primary non-autonomous mechanism for cardiac aging. We show that upd3 is significantly up-regulated in aged oenocytes. Oenocyte-specific knockdown of upd3 is sufficient to block aging-induced cardiac arrhythmia. We further show that the age-dependent induction of upd3 is triggered by impaired peroxisomal import and elevated JNK signaling in aged oenocytes. We term hormonal factors induced by peroxisome dysfunction as peroxikines. Intriguingly, oenocyte-specific overexpression of Pex5, the key peroxisomal import receptor, blocks age-related upd3 induction and alleviates cardiac arrhythmicity. Thus, our studies identify an important role of hepatocyte-specific peroxisomal import in mediating non-autonomous regulation of cardiac aging.
Distinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis
Authors: Verma Kanika , Saxena Kanika , Donaka Rajashekar , Chaphalkar Aseem , Rai Manish Kumar , Shukla Anurag , Zaidi Zainab , Dandage Rohan , Shanmugam Dhanasekaran , Chakraborty Kausik 
Published: June 2020

AbstractMetabolic changes alter the cellular milieu; can this also change intracellular protein folding? Since proteostasis can modulate mutational buffering, if change in metabolism has the ability to change protein folding, arguably, it should also alter mutational buffering. Here we find that altered cellular metabolic states inE. colibuffer distinct mutations on model proteins. Buffered-mutants have folding problems in vivo and are differently chaperoned in different metabolic states. Notably, this assistance is dependent upon the metabolites and not on the increase in canonical chaperone machineries. Being able to reconstitute the folding assistance afforded by metabolites in vitro, we propose that changes in metabolite concentrations have the potential to alter protein folding capacity. Collectively, we unravel that the metabolite pools are bona fide members of proteostasis and aid in mutational buffering. Given the plasticity in cellular metabolism, we posit that metabolic alterations may play an important role in cellular proteostasis.
Impact of alkaloids in food consumption, metabolism and survival in a blood-sucking insect
Authors: Muñoz Ignacio J. , Schilman Pablo E. , Barrozo Romina B. 
Published: June 2020

AbstractThe sense of taste provides information about the “good” or “bad” quality of a food source, which may be potentially nutritious or toxic. Most alkaloids taste bitter to humans, and because bitter taste is synonymous of noxious food, they are generally rejected. This response may be due to an innate low palatability or due to a malaise that occurs after food ingestion, which could even lead to death. We investigated in the kissing bug Rhodnius prolixus, whether alkaloids such as quinine, caffeine and theophylline, are merely distasteful, or if anti-appetitive responses are caused by a post-ingestion physiological effect, or both of these options. Although anti-appetitive responses were observed for the three alkaloids, only caffeine and theophylline affect metabolic and respiratory parameters that reflected an underlying physiological stress following their ingestion. Furthermore, caffeine caused the highest mortality. In contrast, quinine appears to be a merely unpalatable compound. The sense of taste helps insects to avoid making wrong feeding decisions, such as the intake of bitter/toxic foods, and thus avoid potentially harmful effects on health, a mechanism preserved in obligate hematophagous insects.
Genome-enabled phylogenetic and functional reconstruction of an araphid pennate diatom Plagiostriata sp. CCMP470, previously assigned as a radial centric diatom, and its bacterial commensal
Authors: Sato Shinya , Nanjappa Deepak , Dorrell Richard G. , Vieira Fabio Rocha Jimenez , Kazamia Elena , Tirichine Leila , Veluchamy Alaguraj , Heilig Roland , Aury Jean-Marc , Jaillon Olivier , Wincker Patrick , Fussy Zoltan , Obornik Miroslav , Muñoz-Gómez Sergio A. , Mann David G. , Bowler Chris , Zingone Adriana 
Published: June 2020

AbstractDiatoms are an ecologically fundamental and highly diverse group of algae, dominating marine primary production in both open-water and coastal communities. The diatoms include both centric species, which may have radial or polar symmetry, and the pennates, which include raphid and araphid species and arose within the centric lineage. Here, we use combined microscopic and molecular information to reclassify a diatom strain CCMP470, previously annotated as a radial centric species related to Leptocylindrus danicus, as an araphid pennate species in the staurosiroid lineage, within the genus Plagiostriata. CCMP470 shares key ultrastructural features with Plagiostriata taxa, such as the presence of a sternum with parallel striae, and the presence of a highly reduced labiate process on its valve; and this evolutionary position is robustly supported by multigene phylogenetic analysis. We additionally present a draft genome of CCMP470, which is the first genome available for a staurosiroid lineage. 270 Pfams (19%) found in the CCMP470 genome are not known in other diatom genomes, which otherwise does not hold big novelties compared to genomes of non-staurosiroid diatoms. Notably, our DNA library contains the genome of a bacterium within the Rhodobacterales, an alpha-proteobacterial lineage known frequently to associate with algae. We demonstrate the presence of commensal alpha-proteobacterial sequences in other published algal genome and transcriptome datasets, which may indicate widespread and persistent co-occurrence.
Self-healing capacity of fiber-reinforced calcium phosphate cements
Authors: Boehm Anne V. , Meininger Susanne , Gbureck Uwe , Müller Frank A. 
Published: June 2020

AbstractA major problem concerning the mechanical properties of calcium phosphate cements (CPC) is related to their inherent brittleness, which limits their applicability to non-load bearing bone defects. In this work the preparation of a damage tolerant CPC is presented, where the incorporation of functionalized carbon fibers facilitates steady state flat crack propagation with crack openings below 10 µm. A subsequent self-healing process in simulated body fluid, that mimics the in vivo mineralization of bioactive surfaces, closes the cracks and completely restores the mechanical properties. Hereby, two pathways of self-healing are presented: i) intrinsic healing that bases on the inherent bioactive properties of the cement matrix and chemically treated fibers, and ii) capsule based extrinsic healing, where H2PO4- is released as an initiator for the apatite formation. Such damage tolerant CPCs with self-healing capacity are of particular interest to increase the lifetime of implants as well as in the field of load-bearing bioceramics.