bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D pathway related polymorphisms and vitamin D receptor expression in breast cancer
Authors: Francis Issam , AlAbdali Noora , Kapila Kusum , John Bency , Al-Temaimi Rabeah Abbas 
Published: October 2019

Abstract. Vitamin D deficiency is an emerging risk factor for breast cancer suggesting its role in breast cancer pathogenesis. Recent evidence suggests vitamin D receptor (VDR) expression is a prognosis predictor in breast cancer. We set out to determine the status of VDR expression in histologically characterized breast cancers, and whether common genetic variants modify VDR expression in breast cancer. One-hundred and twenty Kuwaiti female breast cancer fixed tissues were assessed for VDR expression to identify the level and location of its expression by immunohistochemistry. VDR variants (rs731236, rs2228570), and vitamin D binding protein ( VDBP) variants (rs4588, rs7041) genotypes were ascertained in breast cancer specimens using Taqman genotyping assays. VDR nuclear expression correlated with low grade tumors (p = 0.01), whereas cytoplasmic expression correlated with lymph node positive tumors (p = 0.03). Absence of VDR expression was a marker for high-grade dedifferentiated tumors (p = 0.01). VDBP rs7041 associated with breast cancer risk (OR 1.92, 95% CI: 1.34 – 2.73; p = 0.0004), and VDR rs2228570 correlated with increased VDR cytoplasmic expression (p < 0.0001). In conclusion, VDR expression is altered in breast cancer confirming its involvement in breast cancer progression. Genetic factors appear to play a role in breast cancer risk, and may modify tumor sensitization to vitamin D.
Hot, volatile‐poor, and oxidized magmatism above the stagnant Pacific plate in Eastern China in the Cenozoic
Authors: Erdmann S. , Chen L.‐H. , Liu J.‐Q. , Xue X.‐Q. , Wang X.‐J. 
Published: October 2019

AbstractEastern China has experienced widespread and voluminous, basaltic to andesitic intraplate magmatism in the Cenozoic. Seismic tomography and kinematic reconstructions show that magmas have erupted above the stagnant Pacific plate, which currently extends within the mantle transition zone for >1500 km beyond the active arc. Seismic studies also show in intriguing detail that low‐velocity wave anomalies reach from the mantle transition zone or below to major volcanic centers, suggesting an intimate relation between the magmatism and components derived from the mantle‐transition zone and possibly from deeper levels. Here, we provide new petrological, mineral chemical, and whole‐rock geochemical data showing that Cenozoic basaltic andesitic and andesitic magmas that have erupted above the present‐day edge of the subducted Pacific plate are largely unfractionated, ≥1130‐1160±15‐50 °C hot, mantle‐derived melts that were volatile‐poor (undegassed melt CO2and H2O of ~2400‐3100±500 ppm and ~0.5‐0.6±0.4‐1.1 wt%), and relatively oxidized (~FMQ to ~FMQ+1.3±1.0). We further infer that the magmas were derived by partial melting of oxidized, H2O‐ and CO2‐poor eclogite‐rich sources (~FMQ‐1.0 to ~FMQ). We use this to suggest that the low‐velocity seismic anomalies below Eastern China largely reflect the presence of oxidized and enriched, hot and not necessarily particularly hydrous mantle domains as common interpretation has suggested. This is crucial information for quantifying material flow above and around the subducted Pacific plate and for constraining residence times of subducted components in Eastern Asia and globally.
Progressive Changes in Magma Transport at the Active Serreta Ridge, Azores
Authors: Romer R.H.W. , Beier C. , Haase K.M. , Klügel A. , Hamelin C. 
Published: October 2019

AbstractVolcanism in the Eastern Azores Plateau occurs at large central volcanoes and along subaerial and submarine fissure zones, resulting from a mantle melting anomaly combined with transtensional stresses. Volcanic structures are aligned WNW‐ESE and NW‐SE, reflecting two tectonic stress fields that control the direction of lateral melt transport. Terceira Island is influenced by both stress fields, dividing the island into an eastern and western part. Several submarine volcanic ridges with variable orientations are located west of Santa Bárbara, the youngest central volcano on Terceira. Major, trace element and Sr‐Nd‐Pb‐Hf isotope compositions from submarine lavas and glasses, in part associated with the 1998–2001 Serreta Ridge eruption, vary between different lava suites, suggesting a formation from different mantle sources. Submarine lavas are more primitive than those from Santa Bárbara volcano, indicating that they are not laterally connected with the shallow magma reservoir located in 2‐ to 5‐km depth beneath the central volcano. Mineral thermobarometric data suggest that the older Serreta magmas were laterally transported at depths >5 km from Santa Bárbara predominantly in WNW direction. We propose that lithospheric extension controls magma transport from the central volcano to Serreta Ridge. The youngest Serreta lavas differ from Santa Bárbara and other submarine ridges in having less radiogenic Pb and higher Hf isotope ratios representing a new magma pulse ascending from the mantle. We conclude that lateral magma transport and the morphology of volcanic ridges are controlled by tectonic stresses in the lithosphere, whereas vertical melt transport is initiated by processes in the mantle.
Hydrate‐filled Fracture Formation at Keathley Canyon 151, Gulf of Mexico, and Implications for Non‐vent Sites
Authors: Oti Emma A. , Cook Ann E. , Welch Susan A. , Sheets Julia M. , Crandall Dustin , Rose Kelly , Daigle Hugh 
Published: October 2019

AbstractNear‐vertical hydrate‐filled fractures are found in subseafloor marine muds, at both advective methane vent sites and at sites without obvious methane and fluid advection (non‐vent sites). At non‐vent sites, the mechanisms that transport methane to the fractures and control how hydrate‐filled fractures form are not well understood. However, these mechanisms are important to establish, as most of Earth's natural gas hydrate is likely bound in marine mud systems. Herein, we focus on understanding the origin of hydrate and how fracture form at non‐vent sites by examining previously hydrate‐bearing fractures in conventional cores taken from Keathley Canyon 151, U.S. northern Gulf of Mexico, drilled by the Gas Hydrate Joint Industry Project in 2005. We combine information from well logs, sediment cores, and science party results and add new X‐ray computed tomography of archival sections and scanning electron microcopy of core samples to develop a conceptual model. We propose that locally generated microbial methane is transported via diffusion from small pores in marine mud into biomineralized burrows with larger pore size in a process called short‐range migration. Hydrate forms in burrows once the methane diffuses into them and the dissolved methane concentration exceeds the solubility threshold. When hydrate fills a burrow, heave from additional hydrate growth places stress on the burrow edges, expands the fracture, and creates additional void space in which methane can diffuse and continue forming hydrate. Fractures slowly propagate in the direction of maximum principal stress.
Monitoring Tree Sway as an Indicator of Water Stress
Authors: Ciruzzi Dominick M. , Loheide Steven P. 
Published: October 2019

AbstractUnderstanding and predicting future consequences of increasingly frequent and intense droughts requires improved monitoring of forest response. Over the course of a day, tree mass and stiffness respond dynamically to changing atmospheric and hydraulic conditions. By conducting a 24‐hr experiment, we sought to disentangle the effects of changing mass and stiffness on tree sway period. We observed that tree mass and stiffness are influenced by changes in tree water content and that diurnal changes in tree sway period are chiefly driven by the loss and recovery of tree stiffness. Over a season‐long time series in twoQuercus rubra(red oak) trees, we observed more pronounced and substantially higher midday increases (+7%) in sway period during days with the driest soil moisture (<0.09) as compared to days when soils were wetter. These findings suggest that continuously monitoring tree sway period offers an innovative approach to detecting water stress in trees.
Transient Brittle‐Ductile Transition Depth Induced by Moderate‐Large Earthquakes in Southern and Baja California
Authors: Cheng Yifang , Ben‐Zion Yehuda 
Published: October 2019

AbstractWe analyze space‐time variations in the depth distribution of seismicity in Southern and Baja California, focusing on transients following four M ≥ 6.7 mainshocks. The regular brittle‐ductile transition depth is estimated at different locations as the local bottom of 99,636 background events and is compared with the bottom of events within earthquake clusters. The four M ≥ 6.7 mainshock‐aftershock sequences exhibit early aftershocks with depths up to 5 km below the regular brittle‐ductile transition depth and epicentral distances up to 15 km from the mainshock ruptures. The maximum aftershock depth increases abruptly following the mainshocks and recovers to the background level after several years. The wide‐spread deeper‐than‐usual early aftershocks favor classical brittle‐ductile transition over change from unstable to stable frictional response as the mechanism governing the base of the seismogenic zone. Episodic transient deepening of the brittle‐ductile transition following major earthquakes can have important long‐term effects on the lower crust.
Long‐Lasting Latitudinal Four‐Peak Structure in the Nighttime Ionosphere Observed by the Swarm Constellation
Authors: Xiong Chao , Lühr Hermann , Sun Longchang , Luo Weihua , Park Jaeheung , Hong Yu 
Published: October 2019

AbstractIn this study, we provide for the first time observation of the latitudinal four‐peak structure of F region electron density in the nightside ionosphere. The special configuration of Swarm satellites, Swarm B having the chance to resample the regions of Swarm A/C with successively increasing time differences, provides an unprecedented opportunity to check the evolution of these nightside electron density peaks. Overall, the latitudinal four‐peak structures have very low occurrence rates, only 4% of the Swarm orbits. The two mid‐latitude peaks prefer to appear close to ±40° magnetic latitude, while the two low‐latitude peaks appear within ±20° magnetic latitude. Such latitudinal four‐peak structures can persist throughout the night until sunrise hours. No clear seasonal dependence is found for the two mid‐latitude peaks, while the two low‐latitude peaks are almost symmetric about the magnetic equator during equinoxes but are located at slightly higher latitudes in the summer hemisphere around solstices. The two low‐latitude peaks at late‐night hours are believed not to be remnants of the dusk‐side equatorial ionization anomaly (EIA) crests, as (a) example shows that Swarm A/C observe the development of shoulders at the flanks of the two EIA crests after sunset hours, and the shoulders become peaks 3 h later when Swarm B resamples the same region; (b) statistic results reveal that the two low‐latitude peaks during post‐midnight hours do not propagate towards the magnetic equator, as expected for EIA crests, but move slowly poleward. We suggest that the enhanced meridional wind at postmidnight hours is one possible driver for causing such latitudinal four‐peak structure of F region electron density. In addition, the simultaneous magnetic measurements from Swarm satellites are also analyzed, but they show no obvious diamagnetic effect that could help to maintain pressure balance within these electron density peaks.
Clinical significance of TP53 variants as possible secondary findings in tumor-only next-generation sequencing
Authors: Yamamoto Yoshihiro , Kanai Masashi , Kou Tadayuki , Sugiyama Aiko , Nakamura Eijiro , Miyake Hidehiko , Yamada Takahiro , Nishigaki Masakazu , Kondo Tomohiro , Murakami Hiromi , Torishima Masako , Matsumoto Shigemi , Kosugi Shinji , Muto Manabu 
Published: October 2019

Abstract
In tumor-only next-generation sequencing (NGS), identified variants have the potential to be secondary findings (SFs), but they require verification through additional germline testing. In the present study, 194 patients with advanced cancer who underwent tumor-only NGS between April 2015 and March 2018 were enrolled, and the incidences of possible and true SFs were evaluated. Among them, 120 patients (61.9%) harbored at least one possible SF. TP53 was the most frequent gene in which 97 variants were found in 91 patients (49.5%). Nine patients provided informed consent to undergo additional germline testing, and a total of 14 variants (BRCA1, n = 1; BRCA2, n = 2; PTEN, n = 2; RB1, n = 1; SMAD4, n = 1; STK11, n = 1; TP53, n = 6) were analyzed. Three variants (BRCA1, n = 1; BRCA2, n = 2) were confirmed to be SFs, whereas TP53 variants were confirmed to be somatic variants. To confirm the low prevalence of SFs in TP53, we analyzed 24 patients with TP53 variants who underwent a paired tumor–normal NGS assay. As expected, all TP53 variants were confirmed to be somatic variants. A total of 30 patients were tested for germline variants in TP53, but none of them resulted in true SFs, suggesting the low prevalence of SFs in this gene. Therefore, the significance of additional germline testing for TP53 variants appears to be relatively low in daily clinical practice using a tumor-only NGS assay, unless patients have any relevant medical or family history.
How we use venetoclax with hypomethylating agents for the treatment of newly diagnosed patients with acute myeloid leukemia
Authors: Jonas Brian A. , Pollyea Daniel A. 
Published: October 2019

AbstractAcute myeloid leukemia (AML) is associated with poor outcomes, especially in older patients in whom the disease is most common. B-cell lymphoma 2 (BCL-2) is an antiapoptotic protein involved in the survival and maintenance of AML, and it is overexpressed in the leukemia stem cell population. Venetoclax is an oral BCL-2 protein inhibitor recently approved by the United States Food and Drug Administration (FDA) for use in combination with a hypomethylating agent (HMA) (azacitidine or decitabine) or low-dose cytarabine for front-line treatment of AML in older patients or those unfit for induction chemotherapy. Given that its mechanism of action is unique, it is not surprising that this widely effective therapy presents unique challenges, including but not limited to the rapidity of responses, the rate and depth of cytopenias, and issues related to drug–drug interactions. With the recent FDA approval and increasingly widespread use, we aim here to summarize, based on evidence and experience, emerging management strategies for the combination of HMAs and venetoclax in the treatment of AML.
Narrowing down the region responsible for 1q23.3q24.1 microdeletion by identifying the smallest deletion
Authors: Hoshina Takao , Seto Toshiyuki , Shimono Taro , Sakamoto Hiroaki , Okuyama Torayuki , Hamazaki Takashi , Yamamoto Toshiyuki 
Published: October 2019

AbstractInterstitial deletions of 1q23.3q24.1 are rare. Here, chromosomal microarray testing identified a de novo microdeletion of arr[GRCh37]1q23.3q24.1(164816055_165696996) × 1 in a patient with moderate developmental delay, hearing loss, cryptorchidism, and other distinctive features. The clinical features were common to those previously reported in patients with overlapping deletions. The patient’s deletion size was 881 kb—the smallest yet reported. This therefore narrowed down the deletion responsible for the common clinical features. The deleted region included seven genes; deletion of LMX1A, RXRG, and ALDH9A1 may have caused our patient’s neurodevelopmental delay.
Ultrahigh β-phase content poly(vinylidene fluoride) with relaxor-like ferroelectricity for high energy density capacitors
Authors: Meng Nan , Ren Xintong , Santagiuliana Giovanni , Ventura Leonardo , Zhang Han , Wu Jiyue , Yan Haixue , Reece Michael J , Bilotti Emiliano 
Published: October 2019

AbstractPoly(vinylidene fluoride)-based dielectric materials are prospective candidates for high power density electric storage applications because of their ferroelectric nature, high dielectric breakdown strength and superior processability. However, obtaining a polar phase with relaxor-like behavior in poly(vinylidene fluoride), as required for high energy storage density, is a major challenge. To date, this has been achieved using complex and expensive synthesis of copolymers and terpolymers or via irradiation with high-energy electron-beam or γ-ray radiations. Herein, a facile process of pressing-and-folding is proposed to produce β-poly(vinylidene fluoride) (β-phase content: ~98%) with relaxor-like behavior observed in poly(vinylidene fluoride) with high molecular weight > 534 kg mol−1, without the need of any hazardous gases, solvents, electrical or chemical treatments. An ultra-high energy density (35 J cm−3) with a high efficiency (74%) is achieved in a pressed-and-folded poly(vinylidene fluoride) (670-700 kg mol−1), which is higher than that of other reported polymer-based dielectric capacitors to the best of our knowledge.
Rapid multiple-quantum three-dimensional fluorescence spectroscopy disentangles quantum pathways
Authors: Mueller Stefan , Lüttig Julian , Malý Pavel , Ji Lei , Han Jie , Moos Michael , Marder Todd B. , Bunz Uwe H. F. , Dreuw Andreas , Lambert Christoph , Brixner Tobias 
Published: October 2019

AbstractCoherent two-dimensional spectroscopy is a powerful tool for probing ultrafast quantum dynamics in complex systems. Several variants offer different types of information but typically require distinct beam geometries. Here we introduce population-based three-dimensional (3D) electronic spectroscopy and demonstrate the extraction of all fourth- and multiple sixth-order nonlinear signal contributions by employing 125-fold (1⨯5⨯5⨯5) phase cycling of a four-pulse sequence. Utilizing fluorescence detection and shot-to-shot pulse shaping in single-beam geometry, we obtain various 3D spectra of the dianion of TIPS-tetraazapentacene, a fluorophore with limited stability at ambient conditions. From this, we recover previously unknown characteristics of its electronic two-photon state. Rephasing and nonrephasing sixth-order contributions are measured without additional phasing that hampered previous attempts using noncollinear geometries. We systematically resolve all nonlinear signals from the same dataset that can be acquired in 8 min. The approach is generalizable to other incoherent observables such as external photoelectrons, photocurrents, or photoions.
Sialic acid mediated mechanical activation of β2 adrenergic receptors by bacterial pili
Authors: Virion Zoe , Doly Stéphane , Saha Kusumika , Lambert Mireille , Guillonneau François , Bied Camille , Duke Rebecca M. , Rudd Pauline M. , Robbe-Masselot Catherine , Nassif Xavier , Coureuil Mathieu , Marullo Stefano 
Published: October 2019

AbstractMeningococcus utilizes β-arrestin selective activation of endothelial cell β2 adrenergic receptor (β2AR) to cause meningitis in humans. Molecular mechanisms of receptor activation by the pathogen and of its species selectivity remained elusive. We report that β2AR activation requires two asparagine-branched glycan chains with terminally exposed N-acetyl-neuraminic acid (sialic acid, Neu5Ac) residues located at a specific distance in its N-terminus, while being independent of surrounding amino-acid residues. Meningococcus triggers receptor signaling by exerting direct and hemodynamic-promoted traction forces on β2AR glycans. Similar activation is recapitulated with beads coated with Neu5Ac-binding lectins, submitted to mechanical stimulation. This previously unknown glycan-dependent mode of allosteric mechanical activation of a G protein-coupled receptor contributes to meningococcal species selectivity, since Neu5Ac is only abundant in humans due to the loss of CMAH, the enzyme converting Neu5Ac into N-glycolyl-neuraminic acid in other mammals. It represents an additional mechanism of evolutionary adaptation of a pathogen to its host.
Core-level nonlinear spectroscopy triggered by stochastic X-ray pulses
Authors: Kayser Yves , Milne Chris , Juranić Pavle , Sala Leonardo , Czapla-Masztafiak Joanna , Follath Rolf , Kavčič Matjaž , Knopp Gregor , Rehanek Jens , Błachucki Wojciech , Delcey Mickaël G. , Lundberg Marcus , Tyrała Krzysztof , Zhu Diling , Alonso-Mori Roberto , Abela Rafael , Sá Jacinto , Szlachetko Jakub 
Published: October 2019

AbstractStochastic processes are highly relevant in research fields as different as neuroscience, economy, ecology, chemistry, and fundamental physics. However, due to their intrinsic unpredictability, stochastic mechanisms are very challenging for any kind of investigations and practical applications. Here we report the deliberate use of stochastic X-ray pulses in two-dimensional spectroscopy to the simultaneous mapping of unoccupied and occupied electronic states of atoms in a regime where the opacity and transparency properties of matter are subject to the incident intensity and photon energy. A readily transferable matrix formalism is presented to extract the electronic states from a dataset measured with the monitored input from a stochastic excitation source. The presented formalism enables investigations of the response of the electronic structure to irradiation with intense X-ray pulses while the time structure of the incident pulses is preserved.
Site-selective remote C(sp3)–H heteroarylation of amides via organic photoredox catalysis
Authors: Chen Hui , Fan Wenjing , Yuan Xiang-Ai , Yu Shouyun 
Published: October 2019

AbstractRadical translocation processes triggered by nitrogen-centered radicals (NCRs), such as 1,5-hydrogen atom transfers (1,5-HAT), demonstrated by the well-established Hofmann-Löffler-Freytag (HLF) reaction, provide an attractive approach for the controllable and selective functionalization of remote inert C(sp3)–H bonds. Here we report an amidyl radical-triggered site-selective remote C(sp3)–H heteroarylation of amides under organic photoredox conditions. This approach provides a mild and highly regioselective reaction affording remote C(sp3)–H heteroarylated amides at room temperature under transition-metal free, weakly basic, and redox-neutral conditions. Non-prefunctionalized heteroarenes, such as purines, thiazolopyridines, benzoxazole, benzothiazoles, benzothiophene, benzofuran, thiazoles and quinoxalines, can be alkylated directly. Sequential and orthogonal C–H functionalization of different heteroarenes by taking advantage pH value or polarity of radicals has also been achieved. DFT calculations explain and can predict the site-selectivity and reactivity of this reaction. This strategy expands the scope of the Minisci reaction and serves as its alternative and potential complement.
Schools of skyrmions with electrically tunable elastic interactions
Authors: Sohn Hayley R. O. , Liu Changda D. , Smalyukh Ivan I. 
Published: October 2019

AbstractCoexistence of order and fluidity in soft matter often mimics that in biology, allowing for complex dynamics and applications-like displays. In active soft matter, emergent order can arise because of such dynamics. Powered by local energy conversion, this behavior resembles motions in living systems, like schooling of fish. Similar dynamics at cellular levels drive biological processes and generate macroscopic work. Inanimate particles capable of such emergent behavior could power nanomachines, but most active systems have biological origins. Here we show that thousands-to-millions of topological solitons, dubbed “skyrmions”, while each converting macroscopically-supplied electric energy, exhibit collective motions along spontaneously-chosen directions uncorrelated with the direction of electric field. Within these “schools” of skyrmions, we uncover polar ordering, reconfigurable multi-skyrmion clustering and large-scale cohesion mediated by out-of-equilibrium elastic interactions. Remarkably, this behavior arises under conditions similar to those in liquid crystal displays and may enable dynamic materials with strong emergent electro-optic responses.