bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian Inference for Solar Flare Extremes
Authors: Griffiths B. , Fawcett L. , Green A. C. 
Published: February 2022

AbstractWhile solar flares are a frequent occurrence, extreme flares are much rarer events and have the potential to cause disruption to life on Earth. In this paper we use Extreme Value Theory to model extreme solar flares, with inference performed in the Bayesian paradigm. The data used have been provided by the National Oceanic and Atmospheric Organisation and consist of recordings of peak flux measurements. After proposing several methods for analysis and selecting our preferred technique—which substantially increases the precision of estimates of key quantities of interest—we improve upon this technique still further by considering the use of informative prior distributions. Doing so, we estimate that a Halloween‐type solar event, and a Carrington‐type event, might occur once (on average) every 49 (29, 85) and 92 (50, 176) years respectively (95% credible intervals shown in parentheses). These findings are similar to those obtained by Tsiftsi and De la Luz (2018), https://doi.org/10.1029/2018SW001958 and Elvidge and Angling (2018), https://doi.org/10.1002/2017SW001727 however, the confidence intervals obtained in both are substantially wider than those found in our study, lending increased certainty to the estimated time between events of such magnitude in our work. We argue that taking the extremal index into account, even when this measure indicates weak temporal dependence, is beneficial to the analysis.
Estrogen-mediated downregulation of HIF-1α signaling in B lymphocytes influences postmenopausal bone loss
Authors: Meng Xianyi , Lin Zhen , Cao Shan , Janowska Iga , Sonomoto Koshiro , Andreev Darja , Katharina Knab , Wen Jinming , Knaup Karl Xaver , Wiesener Michael Sean , Krönke Gerhard , Rizzi Marta , Schett Georg , Bozec Aline 
Published: February 2022

AbstractIn the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and high-throughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice. Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells. The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis. Induction of HSP70 expression by geranylgeranylacetone (GGA) administration alleviates ovariectomy-induced osteoporosis. Moreover, RANKL gene expression has a positive correlation with HIF1A expression in human B cells. In conclusion, HIF-1α signaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.
HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples
Authors: Loi Eleonora , Zavattari Cesare , Tommasi Alessandro , Moi Loredana , Canale Matteo , Po Agnese , Sabato Claudia , Vega-Benedetti Ana Florencia , Ziranu Pina , Puzzoni Marco , Lai Eleonora , Faloppi Luca , Rullán María , Carrascosa Juan , Amat Irene , Urman Jesús M. , Arechederra Maria , Berasain Carmen , Ferretti Elisabetta , Casadei-Gardini Andrea , Avila Matías A. , Alonso Sergio , Scartozzi Mario , Zavattari Patrizia 
Published: February 2022

Abstract
Background
Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations.

Methods
Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR.

Results
We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples.

Conclusions
We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.
Visible light-driven efficient palladium catalyst turnover in oxidative transformations within confined frameworks
Authors: Li Jiawei , He Liuqing , Liu Qiong , Ren Yanwei , Jiang Huanfeng 
Published: February 2022

AbstractPalladium catalyst turnover by reoxidation of a low-valent Pd species dominates the proceeding of an efficient oxidative transformation, but the state-of-the-art catalysis approaches still have great challenges from the perspectives of high efficiency, atom-economy and environmental-friendliness. Herein, we report a new strategy for addressing Pd reoxidation problem by the fabrication of spatially proximate IrIII photocatalyst and PdII catalyst into metal-organic framework (MOF), affording MOFs based Pd/photoredox catalysts UiO-67-Ir-PdX2 (X = OAc, TFA), which are systematically evaluated using three representative Pd-catalyzed oxidation reactions. Owing to the stabilization of single-site Pd and Ir catalysts by MOFs framework as well as the proximity of them favoring fast electron transfer, UiO-67-Ir-PdX2, under visible light, exhibits up to 25 times of Pd catalyst turnover number than the existing catalysis systems. Mechanism investigations theoretically corroborate the capability of MOFs based Pd/photoredox catalysis to regulate the competitive processes of Pd0 aggregation and reoxidation in Pd-catalyzed oxidation reactions.
Forest fragmentation impacts the seasonality of Amazonian evergreen canopies
Authors: Nunes Matheus Henrique , Camargo José Luís Campana , Vincent Grégoire , Calders Kim , Oliveira Rafael S. , Huete Alfredo , Mendes de Moura Yhasmin , Nelson Bruce , Smith Marielle N. , Stark Scott C. , Maeda Eduardo Eiji 
Published: February 2022

AbstractPredictions of the magnitude and timing of leaf phenology in Amazonian forests remain highly controversial. Here, we use terrestrial LiDAR surveys every two weeks spanning wet and dry seasons in Central Amazonia to show that plant phenology varies strongly across vertical strata in old-growth forests, but is sensitive to disturbances arising from forest fragmentation. In combination with continuous microclimate measurements, we find that when maximum daily temperatures reached 35 °C in the latter part of the dry season, the upper canopy of large trees in undisturbed forests lost plant material. In contrast, the understory greened up with increased light availability driven by the upper canopy loss, alongside increases in solar radiation, even during periods of drier soil and atmospheric conditions. However, persistently high temperatures in forest edges exacerbated the upper canopy losses of large trees throughout the dry season, whereas the understory in these light-rich environments was less dependent on the altered upper canopy structure. Our findings reveal a strong influence of edge effects on phenological controls in wet forests of Central Amazonia.
Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology
Authors: Wittenbecher C. , Cuadrat R. , Johnston L. , Eichelmann F. , Jäger S. , Kuxhaus O. , Prada M. , Del Greco M. F. , Hicks A. A. , Hoffman P. , Krumsiek J. , Hu F. B. , Schulze M. B. 
Published: February 2022

AbstractMetabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.
Designing light-element materials with large effective spin-orbit coupling
Authors: Li Jiayu , Yao Qiushi , Wu Lin , Hu Zongxiang , Gao Boya , Wan Xiangang , Liu Qihang 
Published: February 2022

AbstractSpin-orbit coupling (SOC), which is the core of many condensed-matter phenomena such as nontrivial band gap and magnetocrystalline anisotropy, is generally considered appreciable only in heavy elements. This is detrimental to the synthesis and application of functional materials. Therefore, amplifying the SOC effect in light elements is crucial. Herein, focusing on 3d and 4d systems, we demonstrate that the interplay between crystal symmetry and electron correlation can significantly enhance the SOC effect in certain partially occupied orbital multiplets through the self-consistently reinforced orbital polarization as a pivot. Thereafter, we provide design principles and comprehensive databases, where we list all the Wyckoff positions and site symmetries in all two-dimensional (2D) and three-dimensional crystals that could have enhanced SOC effect. Additionally, we predict nine material candidates from our selected 2D material pool as high-temperature quantum anomalous Hall insulators with large nontrivial band gaps of hundreds of meV. Our study provides an efficient and straightforward way for predicting promising SOC-active materials, relieving the use of heavy elements for next-generation spin-orbitronic materials and devices.
Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites
Authors: Paul Atanu , Annunziato Stefano , Lu Bo , Sun Tianliang , Evrova Olivera , Planas-Paz Lara , Orsini Vanessa , Terracciano Luigi M. , Charlat Olga , Loureiro Zinger Yang , Ji Lei , Zamponi Raffaella , Sigoillot Frederic , Lei Hong , Lindeman Alicia , Russ Carsten , Reece-Hoyes John S. , Nicholson Thomas B. , Tchorz Jan S. , Cong Feng 
Published: February 2022

AbstractThe Hippo/YAP pathway controls cell proliferation through sensing physical and spatial organization of cells. How cell-cell contact is sensed by Hippo signaling is poorly understood. Here, we identified the cell adhesion molecule KIRREL1 as an upstream positive regulator of the mammalian Hippo pathway. KIRREL1 physically interacts with SAV1 and recruits SAV1 to cell-cell contact sites. Consistent with the hypothesis that KIRREL1-mediated cell adhesion suppresses YAP activity, knockout of KIRREL1 increases YAP activity in neighboring cells. Analyzing pan-cancer CRISPR proliferation screen data reveals KIRREL1 as the top plasma membrane protein showing strong correlation with known Hippo regulators, highlighting a critical role of KIRREL1 in regulating Hippo signaling and cell proliferation. During liver regeneration in mice, KIRREL1 is upregulated, and its genetic ablation enhances hepatic YAP activity, hepatocyte reprogramming and biliary epithelial cell proliferation. Our data suggest that KIRREL1 functions as a feedback regulator of the mammalian Hippo pathway through sensing cell-cell interaction and recruiting SAV1 to cell-cell contact sites.
Mantle Hg isotopic heterogeneity and evidence of oceanic Hg recycling into the mantle
Authors: Yin Runsheng , Chen Di , Pan Xin , Deng Changzhou , Chen Liemeng , Song Xieyan , Yu Songyue , Zhu Chuanwei , Wei Xun , Xu Yue , Feng Xinbin , Blum Joel D. , Lehmann Bernd 
Published: February 2022

AbstractThe geochemical cycle of mercury in Earth’s surface environment (atmosphere, hydrosphere, biosphere) has been extensively studied; however, the deep geological cycling of this element is less well known. Here we document distinct mass-independent mercury isotope fractionation (expressed as Δ199Hg) in island arc basalts and mid-ocean ridge basalts. Both rock groups show positive Δ199Hg values up to 0.34‰ and 0.22‰, respectively, which deviate from recent estimates of the primitive mantle (Δ199Hg: 0.00 ± 0.10‰, 2 SD)1. The positive Δ199Hg values indicate recycling of marine Hg into the asthenospheric mantle. Such a crustal Hg isotope signature was not observed in our samples of ocean island basalts and continental flood basalts, but has recently been identified in canonical end-member samples of the deep mantle1, therefore demonstrating that recycling of mercury can affect both the upper and lower mantle. Our study reveals large-scale translithospheric Hg recycling via plate tectonics.
Photochemistry of the pyruvate anion produces CO2, CO, CH3–, CH3, and a low energy electron
Authors: Clarke Connor J. , Gibbard Jemma A. , Hutton Lewis , Verlet Jan R. R. , Curchod Basile F. E. 
Published: February 2022

AbstractThe photochemistry of pyruvic acid has attracted much scientific interest because it is believed to play critical roles in atmospheric chemistry. However, under most atmospherically relevant conditions, pyruvic acid deprotonates to form its conjugate base, the photochemistry of which is essentially unknown. Here, we present a detailed study of the photochemistry of the isolated pyruvate anion and uncover that it is extremely rich. Using photoelectron imaging and computational chemistry, we show that photoexcitation by UVA light leads to the formation of CO2, CO, and CH3−. The observation of the unusual methide anion formation and its subsequent decomposition into methyl radical and a free electron may hold important consequences for atmospheric chemistry. From a mechanistic perspective, the initial decarboxylation of pyruvate necessarily differs from that in pyruvic acid, due to the missing proton in the anion.
TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence
Authors: Farfariello Valerio , Gordienko Dmitri V. , Mesilmany Lina , Touil Yasmine , Germain Emmanuelle , Fliniaux Ingrid , Desruelles Emilie , Gkika Dimitra , Roudbaraki Morad , Shapovalov George , Noyer Lucile , Lebas Mathilde , Allart Laurent , Zienthal-Gelus Nathalie , Iamshanova Oksana , Bonardi Franck , Figeac Martin , Laine William , Kluza Jerome , Marchetti Philippe , Quesnel Bruno , Metzger Daniel , Bernard David , Parys Jan B. , Lemonnier Loïc , Prevarskaya Natalia 
Published: February 2022

AbstractCellular senescence is implicated in a great number of diseases including cancer. Although alterations in mitochondrial metabolism were reported as senescence drivers, the underlying mechanisms remain elusive. We report the mechanism altering mitochondrial function and OXPHOS in stress-induced senescent fibroblasts. We demonstrate that TRPC3 protein, acting as a controller of mitochondrial Ca2+ load via negative regulation of IP3 receptor-mediated Ca2+ release, is down regulated in senescence regardless of the type of senescence inducer. This remodelling promotes cytosolic/mitochondrial Ca2+ oscillations and elevates mitochondrial Ca2+ load, mitochondrial oxygen consumption rate and oxidative phosphorylation. Re-expression of TRPC3 in senescent cells diminishes mitochondrial Ca2+ load and promotes escape from OIS-induced senescence. Cellular senescence evoked by TRPC3 downregulation in stromal cells displays a proinflammatory and tumour-promoting secretome that encourages cancer epithelial cell proliferation and tumour growth in vivo. Altogether, our results unravel the mechanism contributing to pro-tumour behaviour of senescent cells.
Prognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications
Authors: Al-Nesf Maryam A. Y. , Abdesselem Houari B. , Bensmail Ilham , Ibrahim Shahd , Saeed Walaa A. H. , Mohammed Sara S. I. , Razok Almurtada , Alhussain Hashim , Aly Reham M. A. , Al Maslamani Muna , Ouararhni Khalid , Khatib Mohamad Y. , Hssain Ali Ait , Omrani Ali S. , Al-Kaabi Saad , Al Khal Abdullatif , Al-Thani Asmaa A. , Samsam Waseem , Farooq Abdulaziz , Al-Suwaidi Jassim , Al-Maadheed Mohammed , Al-Siddiqi Heba H. , Butler Alexandra E. , Decock Julie V. , Mohamed-Ali Vidya , Al-Ejeh Fares 
Published: February 2022

AbstractCOVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients.
Estrogen receptor beta repurposes EZH2 to suppress oncogenic NFκB/p65 signaling in triple negative breast cancer
Authors: Aspros Kirsten G. M. , Carter Jodi M. , Hoskin Tanya L. , Suman Vera J. , Subramaniam Malayannan , Emch Michael J. , Ye Zhenqing , Sun Zhifu , Sinnwell Jason P. , Thompson Kevin J. , Tang Xiaojia , Rodman Esther P. B. , Wang Xiyin , Nelson Adam W. , Chernukhin Igor , Hamdan Feda H. , Bruinsma Elizabeth S. , Carroll Jason S. , Fernandez-Zapico Martin E. , Johnsen Steven A. , Kalari Krishna R. , Huang Haojie , Leon-Ferre Roberto A. , Couch Fergus J. , Ingle James N. , Goetz Matthew P. , Hawse John R. 
Published: February 2022

AbstractTriple Negative Breast Cancer (TNBC) accounts for 15–20% of all breast cancer cases, yet is responsible for a disproportionately high percentage of breast cancer mortalities. Thus, there is an urgent need to identify novel biomarkers and therapeutic targets based on the molecular events driving TNBC pathobiology. Estrogen receptor beta (ERβ) is known to elicit anti-cancer effects in TNBC, however its mechanisms of action remain elusive. Here, we report the expression profiles of ERβ and its association with clinicopathological features and patient outcomes in the largest cohort of TNBC to date. In this cohort, ERβ was expressed in approximately 18% of TNBCs, and expression of ERβ was associated with favorable clinicopathological features, but correlated with different overall survival outcomes according to menopausal status. Mechanistically, ERβ formed a co-repressor complex involving enhancer of zeste homologue 2/polycomb repressive complex 2 (EZH2/PRC2) that functioned to suppress oncogenic NFκB/RELA (p65) activity. Importantly, p65 was shown to be required for formation of this complex and for ERβ-mediated suppression of TNBC. Our findings indicate that ERβ+ tumors exhibit different characteristics compared to ERβ− tumors and demonstrate that ERβ functions as a molecular switch for EZH2, repurposing it for tumor suppressive activities and repression of oncogenic p65 signaling.
Tracing transport of protein aggregates in microgravity versus unit gravity crystallization
Authors: Martirosyan Arayik , Falke Sven , McCombs Deborah , Cox Martin , Radka Christopher D. , Knop Jan , Betzel Christian , DeLucas Lawrence J. 
Published: February 2022

AbstractMicrogravity conditions have been used to improve protein crystallization from the early 1980s using advanced crystallization apparatuses and methods. Early microgravity crystallization experiments confirmed that minimal convection and a sedimentation-free environment is beneficial for growth of crystals with higher internal order and in some cases, larger volume. It was however realized that crystal growth in microgravity requires additional time due to slower growth rates. The progress in space research via the International Space Station (ISS) provides a laboratory-like environment to perform convection-free crystallization experiments for an extended time. To obtain detailed insights in macromolecular transport phenomena under microgravity and the assumed reduction of unfavorable impurity incorporation in growing crystals, microgravity and unit gravity control experiments for three different proteins were designed. To determine the quantity of impurity incorporated into crystals, fluorescence-tagged aggregates of the proteins (acting as impurities) were prepared. The recorded fluorescence intensities of the respective crystals reveal reduction in the incorporation of aggregates under microgravity for different aggregate quantities. The experiments and data obtained, provide insights about macromolecular transport in relation to molecular weight of the target proteins, as well as information about associated diffusion behavior and crystal lattice formation. Results suggest one explanation why microgravity-grown protein crystals often exhibit higher quality. Furthermore, results from these experiments can be used to predict which proteins may benefit more from microgravity crystallization.
Corrosion behavior of an in situ consolidated nanocrystalline Al-V alloy
Authors: Witharamage C. S. , Christudasjustus J. , Smith J. , Gao W. , Gupta R. K. 
Published: February 2022

AbstractSupersaturated solid solutions of Al and corrosion-resistant alloying elements (M: V, Mo, Cr, Ti, Nb), produced by non-equilibrium processing techniques, have been reported to exhibit high corrosion resistance and strength. The corrosion mechanism for such improved corrosion performance has not been well understood. We present a fundamental understanding of the role of V in corrosion of an Al-V alloy, which will provide a theoretical background for developing corrosion-resistant Al alloys. High-energy ball milling of the elemental powder of Al and V produced an in situ consolidated Al-V alloy, which exhibited high solid solubility of V. The corrosion resistance of Al-V alloy was significantly higher than that of pure Al, which was attributed to the (1) enrichment of V at the passive film/substrate interface, (2) incorporation of V into the passive film, and (3) deposition of V on the iron-containing cathodic particles and therefore, retardation of cathodic reaction.