bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of Crustal Melt Bodies at the Hot Spot‐Influenced Section of the Galápagos Spreading Centre From Seismic Reflection Images
Authors: Boddupalli B. , Canales J.P. 
Published: May 2019

AbstractAccretion of the lower crust at mid‐ocean ridges is a debated topic, with modern seismic observations pointing to a complex magmatic system that includes an axial multisill system of middle‐ and lower‐crustal melt lenses and near‐ and off‐axis melt bodies. Here we revisit the hot spot‐influenced section of the western Galápagos Spreading Centre and reprocess multichannel seismic reflection data using a wide‐angle seismic tomography model. Our new images show that the magma reservoir in the lower crust at this ridge section is intruded with partially molten melt lenses. The images also show evidence for off‐axis melt lenses, magmatic‐hydrothermal interactions and Moho reflections in this region. We conclude that the similarities between the axial crustal structure of this hot spot‐influenced mid‐ocean ridge and the multisill magmatic structure imaged at the East Pacific Rise indicate that these features are common along the global mid‐ocean ridge system where seafloor spreading is dominated by magmatic accretion.
Active Boulder Movement at High Martian Latitudes
Authors: Dundas Colin M. , Mellon Michael T. , Conway Susan J. , Gastineau Renaldo 
Published: May 2019

AbstractLobate stony landforms occur on steep slopes at high latitudes on Mars. We demonstrate active boulder movement at seven such sites. Submeter‐scale boulders frequently move distances of a few meters. The movement is concentrated in the vicinity of the lobate landforms but also occurs on other slopes. This provides evidence for a newly discovered, common style of activity on Mars, which may play an important role in slope degradation. It also opens the possibility that the lobate features are currently forming in the absence of significant volumes of liquid water.
Modeling Wind‐Driven Ionospheric Dynamo Currents at Mars: Expectations for InSight Magnetic Field Measurements
Authors: Lillis Robert J. , Fillingim Matthew O. , Ma Yingjuan , Gonzalez‐Galindo Francisco , Forget François , Johnson Catherine L. , Mittelholz Anna , Russell Christopher T. , Andersson Laila , Fowler Christopher M. 
Published: May 2019

AbstractWe model expected dynamo currents above, and resulting magnetic field profiles at, InSight's landing site on Mars, including for the first time the effect of electron‐ion collisions. We calculate their diurnal and seasonal variability using inputs from global models of the Martian thermosphere, ionosphere, and magnetosphere. Modeled currents primarily depend on plasma densities and the strength of the neutral wind component perpendicular to the combined crustal and draped magnetic fields that thread the ionosphere. Negligible at night, currents are the strongest in the late morning and near solstices due to stronger winds and near perihelion due to both stronger winds and higher plasma densities from solar EUV photoionization. Resulting surface magnetic fields of tens of nanotesla and occasionally >100 nT may be expected at the InSight landing site. We expect currents and surface fields to vary significantly with changes in the draped magnetic field caused by Mars' dynamic solar wind environment.
U.S. East Coast Lidar Measurements Show Offshore Wind Turbines Will Encounter Very Low Atmospheric Turbulence
Authors: Bodini Nicola , Lundquist Julie K. , Kirincich Anthony 
Published: May 2019

AbstractThe rapid growth of offshore wind energy requires accurate modeling of the wind resource, which can be depleted by wind farm wakes. Turbulence dissipation rate (ϵ) governs the accuracy of model predictions of hub‐height wind speed and the development and erosion of wakes. Here we assess the variability of turbulence kinetic energy and ϵ using 13 months of observations from a profiling lidar deployed on a platform off the Massachusetts coast. Offshore, ϵ is 2 orders of magnitude smaller than onshore, with a subtle diurnal cycle. Wind direction influences the annual cycle of turbulence, with larger values in winter when the wind flows from the land, and smaller values in summer, when the wind flows from open ocean. Because of the weak turbulence, wind plant wakes will be stronger and persist farther downwind in summer.
Modeling Contributions of Continents and Oceans to the Diurnal Variation of the Global Electric Circuit
Authors: Slyunyaev Nikolay N. , Ilin Nikolay V. , Mareev Evgeny A. 
Published: May 2019

AbstractContributions of different land and ocean regions to the diurnal variation of the global electric circuit are simulated using the Weather Research and Forecasting model by estimating the ionospheric potential produced by thunderstorms and electrified shower clouds in each grid column. The model predicts that contributions from land regions have maxima at about 14:00–18:00 local time (LT), whereas contributions from oceans have maxima at about 2:00–6:00 LT, and different ocean regions show nearly the same relative diurnal variation. It is remarkable that contributions from ocean regions with many islands (Maritime Continent and Middle America) have maxima at both 14:00–18:00 and 2:00–6:00 LT.
Ion‐Neutral Coupling in the Upper Atmosphere of Mars: A Dominant Driver of Topside Ionospheric Structure
Authors: Mayyasi Majd , Narvaez C. , Benna Mehdi , Elrod M. , Mahaffy Paul 
Published: May 2019

AbstractThe structure of the upper atmosphere of Mars provides insights into the physical mechanisms that drive escape of species into outer space. Deviations in plasma density profiles with altitude from the theoretical exponentially decaying formulation have been routinely observed for decades yet remain largely unexplained. Proposed mechanisms driving this variability have focused primarily on plasma‐specific processes, as limited by past plasma‐only observations. The Mars Atmosphere and Volatile Evolution mission's Neutral Gas and Ion Mass Spectrometer data set has recently provided unprecedented planetographic coverage for both ions and neutrals in the Martian upper atmosphere. Ion, electron, and neutral density profiles with altitude, collected on the sun‐lit inbound portion of the spacecraft orbit have been analyzed. It was found that neutral species, measured between ~160 and 200 km, behave consistently with the bulk atmosphere and that variations in ion density profiles follow neutral profile variations at the same altitudes in 70% of the observations. In the remaining 30%, additional structure was apparent in the ionized species' profiles that were found to preferentially lie in regions of strong crustal field or to be measured near dawn. A 1‐D ionospheric model was used to show that many observed features in plasma profiles are directly driven by neutral atmospheric features, providing strong evidence for ion‐neutral coupling in the atmosphere of Mars.
Kelvin‐Helmholtz Waves Magnetic Curvature and Vorticity: Four‐Spacecraft Cluster Observations
Authors: Kieokaew Rungployphan , Foullon Claire 
Published: May 2019

Abstract[1] Magnetopause Kelvin‐Helmholtz (KH) waves are rich in complex magnetic and flow structures which are key to understand the role of these waves in facilitating the solar wind plasma transport into the Earth's magnetosphere. Four spacecraft in tetrahedral configuration provide the tools necessary for characterizing in situ magnetic geometry and vortical flow. We apply the tools on KH waves observed by Cluster inside an electron boundary layer on the duskside magnetopause. Magnetic curvature and flow vorticity properties of the KH waves are obtained for various solar wind conditions. Smaller curvature radius and higher‐positive vorticity are found for longer wavelength. Changes in KH wavelengths observed with relatively fixed tetrahedron size allow us to resolve magnetic curvature in multiscales. For the first time in a space plasma, we report the dependence of the curvature radius measurement on the ratio of the tetrahedron size to the wavelength, consistent with nonlinear spatial variations of magnetic structures that would be resolved by nested cross‐scale spacecraft tetrahedrons. Negative vorticity is found to develop in the rolled‐up vortex, adjacent to positive vorticity in the vortex core. The strength of negative vorticity is found to increase with the solar wind proton density and proton bulk flow speed. This study provides observational evidence of multiscale magnetic structures and is useful for understanding the development of rolled‐up vortex signatures during various stages of solar wind‐controlled KH wave evolution.
Frequency-tunable continuous-wave random lasers at terahertz frequencies
Authors: Biasco Simone , Beere Harvey E. , Ritchie David A. , Li Lianhe , Davies A. Giles , Linfield Edmund H. , Vitiello Miriam S. 
Published: May 2019

AbstractRandom lasers are a class of devices in which feedback arises from multiple elastic scattering in a highly disordered structure, providing an almost ideal light source for artefact-free imaging due to achievable low spatial coherence. However, for many applications ranging from sensing and spectroscopy to speckle-free imaging, it is essential to have high-radiance sources operating in continuous-wave (CW). In this paper, we demonstrate CW operation of a random laser using an electrically pumped quantum-cascade laser gain medium in which a bi-dimensional (2D) random distribution of air holes is patterned into the top metal waveguide. We obtain a highly collimated vertical emission at ~3 THz, with a 430 GHz bandwidth, device operation up to 110 K, peak (pulsed) power of 21 mW, and CW emission of 1.7 mW. Furthermore, we show that an external cavity formed with a movable mirror can be used to tune a random laser, obtaining continuous frequency tuning over 11 GHz.
R406 elicits anti-Warburg effect via Syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells
Authors: Sun Shuxin , Xue Dongdong , Chen Zhijie , Ou-yang Ying , Zhang Ji , Mai Jialuo , Gu Jiayv , Lu Wanjun , Liu Xincheng , Liu Wenfeng , Sheng Longxiang , Lu Bingzheng , Lin Yuan , Xing Fan , Chen Zhongping , Mou Yonggao , Yan Guangmei , Zhu Wenbo , Sai Ke 
Published: May 2019

AbstractGiven that glioma stem cells (GSCs) play a critical role in the initiation and chemoresistance in glioblastoma multiforme (GBM), targeting GSCs is an attractive strategy to treat GBM. Utilizing an anti-cancer compound library, we identified R406, the active metabolite of a FDA-approved Syk inhibitor for immune thrombocytopenia (ITP), with remarkable cytotoxicity against GSCs but not normal neural stem cells. R406 significantly inhibited neurosphere formation and triggered apoptosis in GSCs. R406 induced a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) and subsequently production of excess ROS in GSCs. R406 also diminished tumor growth and efficiently sensitized gliomas to temozolomide in GSC-initiating xenograft mouse models. Mechanistically, the anti-GSC effect of R406 was due to the disruption of Syk/PI3K signaling in Syk-positive GSCs and PI3K/Akt pathway in Syk-negative GSCs respectively. Overall, these findings not only identify R406 as a promising GSC-targeting agent but also reveal the important role of Syk and PI3K pathways in the regulation of energy metabolism in GSCs.
3-deazaneplanocin A protects against cisplatin-induced renal tubular cell apoptosis and acute kidney injury by restoration of E-cadherin expression
Authors: Ni Jun , Hou Xiying , Wang Xueqiao , Shi Yinfeng , Xu Liuqing , Zheng Xiaoqing , Liu Na , Qiu Andong , Zhuang Shougang 
Published: May 2019

Abstract3-deazaneplanocin A (3-DZNeP) has been used as an inhibitor of enhancer of zeste homolog 2 (EZH2). Here, we explore the role and underlying mechanisms action of 3-DZNeP in abrogating cisplatin nephrotoxicity. Exposure of cultured mouse renal proximal tubular epithelial cells (mTECs) to cisplatin resulted in dose and time-dependent cleavage of caspase-3, decrease of cell viability, and increase of histone H3 lysine 27 trimethylation (H3K27me3), whereas expression levels of EZH2, a major methyltransferase of H3K27me3, were not affected. Treatment with 3-DZNeP significantly inhibited cisplatin-induced activation of caspase-3, apoptosis, loss of cell viability but did not alter levels of EZH2 and H3K27me3 in cultured mTECs. 3-DZNeP treatment did not affect activation of extracellular signal-regulated kinase (ERK) 1/2, p38 or c-Jun N-terminal kinases (JNK) 1/2, which contribute to renal epithelial cell death, but caused dose-dependent restoration of E-cadherin in mTECs exposed to cisplatin. Silencing of E-cadherin expression by siRNA abolished the cytoprotective effects of 3-DZNeP. In contrast, 3-DZNeP treatment potentiated the cytotoxic effect of cisplatin in H1299, a non-small cell lung cancer cell line that expresses lower E-cadherin levels. Finally, administration of 3-DZNeP attenuated renal dysfunction, morphological damage, and renal tubular cell death, which was accompanied by E-cadherin preservation, in a mouse model of cisplatin nephrotoxicity. Overall, these data indicate that 3-DZNeP suppresses cisplatin-induced tubular epithelial cell apoptosis and acute kidney injury via an E-cadherin-dependent mechanism, and suggest that combined application of 3-DZNeP with cisplatin would be a novel chemotherapeutic strategy that enhances the anti-tumor effect of cisplatin and reduces its nephrotoxicity.
Kremen1-induced cell death is regulated by homo- and heterodimerization
Authors: Sumia Iffat , Pierani Alessandra , Causeret Frédéric 
Published: May 2019

AbstractIn multicellular organisms, cell death pathways allow the removal of abnormal or unwanted cells. Their dysregulation can lead either to excessive elimination or to inappropriate cell survival. Evolutionary constraints ensure that such pathways are strictly regulated in order to restrain their activation to the appropriate context. We have previously shown that the transmembrane receptor Kremen1 behaves as a dependence receptor, triggering cell death unless bound to its ligand Dickkopf1. In this study, we reveal that Kremen1 apoptotic signaling requires homodimerization of the receptor. Dickkopf1 binding inhibits Kremen1 multimerization and alleviates cell death, whereas forced dimerization increases apoptotic signaling. Furthermore, we show that Kremen2, a paralog of Kremen1, which bears no intrinsic apoptotic activity, binds and competes with Kremen1. Consequently, Kremen2 is a very potent inhibitor of Kremen1-induced cell death. Kremen1 was proposed to act as a tumor suppressor, preventing cancer cell survival in a ligand-poor environment. We found that KREMEN2 expression is increased in a large majority of cancers, suggesting it may confer increased survival capacity. Consistently, low KREMEN2 expression is a good prognostic for patient survival in a variety of cancers.
CXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-α production in systemic sclerosis
Authors: Lande Roberto , Lee Ernest Y. , Palazzo Raffaella , Marinari Barbara , Pietraforte Immacolata , Santos Giancarlo Santiago , Mattenberger Yves , Spadaro Francesca , Stefanantoni Katia , Iannace Nicoletta , Dufour Aleksandra Maria , Falchi Mario , Bianco Manuela , Botti Elisabetta , Bianchi Luca , Alvarez Montserrat , Riccieri Valeria , Truchetet Marie-Elise , C.L. Wong Gerard , Chizzolini Carlo , Frasca Loredana 
Published: May 2019

AbstractSystemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis and vasculopathy. CXCL4 represents an early serum biomarker of severe SSc and likely contributes to inflammation via chemokine signaling pathways, but the exact role of CXCL4 in SSc pathogenesis is unclear. Here, we elucidate an unanticipated mechanism for CXCL4-mediated immune amplification in SSc, in which CXCL4 organizes “self” and microbial DNA into liquid crystalline immune complexes that amplify TLR9-mediated plasmacytoid dendritic cell (pDC)-hyperactivation and interferon-α production. Surprisingly, this activity does not require CXCR3, the CXCL4 receptor. Importantly, we find that CXCL4-DNA complexes are present in vivo and correlate with type I interferon (IFN-I) in SSc blood, and that CXCL4-positive skin pDCs coexpress IFN-I-related genes. Thus, we establish a direct link between CXCL4 overexpression and the IFN-I-gene signature in SSc and outline a paradigm in which chemokines can drastically modulate innate immune receptors without being direct agonists.
High mitogenic stimulation arrests angiogenesis
Authors: Pontes-Quero Samuel , Fernández-Chacón Macarena , Luo Wen , Lunella Federica Francesca , Casquero-Garcia Verónica , Garcia-Gonzalez Irene , Hermoso Ana , Rocha Susana F. , Bansal Mayank , Benedito Rui 
Published: May 2019

AbstractAppropriate therapeutic modulation of endothelial proliferation and sprouting is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The current view is that an increase in growth factor concentration, and the resulting mitogenic activity, increases both endothelial proliferation and sprouting. Here, we modulate mitogenic stimuli in different vascular contexts by interfering with the function of the VEGF and Notch signalling pathways at high spatiotemporal resolution in vivo. Contrary to the prevailing view, our results indicate that high mitogenic stimulation induced by VEGF, or Notch inhibition, arrests the proliferation of angiogenic vessels. This is due to the existence of a bell-shaped dose-response to VEGF and MAPK activity that is counteracted by Notch and p21, determining whether endothelial cells sprout, proliferate, or become quiescent. The identified mechanism should be considered to achieve optimal therapeutic modulation of angiogenesis.
Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly
Authors: Gui Xinrui , Luo Feng , Li Yichen , Zhou Heng , Qin Zhenheng , Liu Zhenying , Gu Jinge , Xie Muyun , Zhao Kun , Dai Bin , Shin Woo Shik , He Jianhua , He Lin , Jiang Lin , Zhao Minglei , Sun Bo , Li Xueming , Liu Cong , Li Dan 
Published: May 2019

AbstractSubcellular membrane-less organelles consist of proteins with low complexity domains. Many of them, such as hnRNPA1, can assemble into both a polydisperse liquid phase and an ordered solid phase of amyloid fibril. The former mirrors biological granule assembly, while the latter is usually associated with neurodegenerative disease. Here, we observe a reversible amyloid formation of hnRNPA1 that synchronizes with liquid–liquid phase separation, regulates the fluidity and mobility of the liquid-like droplets, and facilitates the recruitment of hnRNPA1 into stress granules. We identify the reversible amyloid-forming cores of hnRNPA1 (named hnRACs). The atomic structures of hnRACs reveal a distinct feature of stacking Asp residues, which contributes to fibril reversibility and explains the irreversible pathological fibril formation caused by the Asp mutations identified in familial ALS. Our work characterizes the structural diversity and heterogeneity of reversible amyloid fibrils and illuminates the biological function of reversible amyloid formation in protein phase separation.
Rapid unimolecular reaction of stabilized Criegee intermediates and implications for atmospheric chemistry
Authors: Long Bo , Bao Junwei Lucas , Truhlar Donald G. 
Published: May 2019

AbstractElucidating atmospheric oxidation mechanisms is necessary for estimating the lifetimes of atmospheric species and understanding secondary organic aerosol formation and atmospheric oxidation capacity. We report an unexpectedly fast mechanistic pathway for the unimolecular reactions of large stabilized Criegee intermediates, which involves the formation of bicyclic structures from large Criegee intermediates containing an aldehyde group. The barrier heights of the mechanistic pathways are unexpectedly low – about 2–3 kcal/mol – and are at least 10 kcal/mol lower than those of hydrogen shift processes in large syn Criegee intermediates; and the calculated rate constants show that the mechanistic pathways are 105-109 times faster than those of the corresponding hydrogen shift processes. The present findings indicate that analogous low-energy pathways can now also be expected in other large Criegee intermediates and that oxidative capacity of some Criegee intermediates is smaller than would be predicted by existing models.
A modular degron library for synthetic circuits in mammalian cells
Authors: Chassin Hélène , Müller Marius , Tigges Marcel , Scheller Leo , Lang Moritz , Fussenegger Martin 
Published: May 2019

AbstractTight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells.
Vectorizing the spatial structure of high-harmonic radiation from gas
Authors: Kong F. , Zhang C. , Larocque H. , Li Z. , Bouchard F. , Ko D. H. , Brown G. G. , Korobenko A. , Hammond T. J. , Boyd Robert W. , Karimi E. , Corkum P. B. 
Published: May 2019

AbstractStrong field laser physics has primarily been concerned with controlling beams in time while keeping their spatial profiles invariant. In the case of high harmonic generation, the harmonic beam is the result of the coherent superposition of atomic dipole emissions. Therefore, fundamental beams can be tailored in space, and their spatial characteristics will be imparted onto the harmonics. Here we produce high harmonics using a space-varying polarized fundamental laser beam, which we refer to as a vector beam. By exploiting the natural evolution of a vector beam as it propagates, we convert the fundamental beam into high harmonic radiation at its focus where the polarization is primarily linear. This evolution results in circularly polarized high harmonics in the far field. Such beams will be important for ultrafast probing of magnetic materials.
Inhibition of MYC by the SMARCB1 tumor suppressor
Authors: Weissmiller April M. , Wang Jing , Lorey Shelly L. , Howard Gregory C. , Martinez Ernest , Liu Qi , Tansey William P. 
Published: May 2019

AbstractSMARCB1 encodes the SNF5 subunit of the SWI/SNF chromatin remodeler. SNF5 also interacts with the oncoprotein transcription factor MYC and is proposed to stimulate MYC activity. The concept that SNF5 is a coactivator for MYC, however, is at odds with its role as a tumor-suppressor, and with observations that loss of SNF5 leads to activation of MYC target genes. Here, we reexamine the relationship between MYC and SNF5 using biochemical and genome-wide approaches. We show that SNF5 inhibits the DNA-binding ability of MYC and impedes target gene recognition by MYC in cells. We further show that MYC regulation by SNF5 is separable from its role in chromatin remodeling, and that reintroduction of SNF5 into SMARCB1-null cells mimics the primary transcriptional effects of MYC inhibition. These observations reveal that SNF5 antagonizes MYC and provide a mechanism to explain how loss of SNF5 can drive malignancy.