bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Shear Deformation Zone and the Smoothing of Faults With Displacement
Authors: Perrin Clément , Waldhauser Felix , Scholz Christopher H. 
Published: March 2021

AbstractWe use high‐resolution earthquake locations to characterize the three‐dimensional structure of active faults in California and how it evolves with fault structural maturity. We investigate the distribution of aftershocks of several recent large earthquakes that occurred on continental strike slip faults of various structural maturity (i.e. various cumulative fault displacement, length, initiation age and slip rate). Aftershocks define a tabular zone of shear deformation surrounding the mainshock rupture plane. Comparing this to geological observations, we conclude that this results from the re‐activation of secondary faults. We observe a rapid fall off of the number of aftershocks at a distance range of 0.06‐0.22 km from the main fault surface of mature faults, and 0.6‐1.0 km from the fault surface of immature faults. The total width of the active shear deformation zone surrounding the main fault plane reaches 1.0‐2.5 km and 6‐9 km for mature and immature faults, respectively. We find that the width of the shear deformation zone decreases as a power law with cumulative fault displacement. Comparing with a dynamic rough fault model, we infer that the narrowing of the shear deformation zone agrees quantitatively with earlier estimates of the smoothing of faults with displacement, both of which are aspects of fault wear. We find that earthquake stress drop decreases with fault displacement and hence with increased smoothness and/or slip rate. This may result from fault healing or the effect of roughness on friction.
2D Parametric Model for Surface Wave Development Under Varying Wind Field in Space and Time
Authors: Kudryavtsev Vladimir , Yurovskaya Maria , Chapron Bertrand 
Published: March 2021

AbstractA fully consistent 2D parametric model of wave development under spatially and/or time varying winds is developed. Derived coupled equations are written in their characteristic form to provide practical means to rapidly assess how the energy, frequency and direction of dominant surface waves are developing and distributed under varying wind forcing conditions. For young waves, nonlinear interactions drive the peak frequency downshift, and the wind energy input and wave breaking dissipation are governing the wave energy evolution. With a prescribed wind wave growth rate, proportional to (u*/c) squared, wave breaking dissipation must follow a power‐function of the dominant wave slope. For uniform wind conditions, this choice for the growth rate imposes solutions to follow fetch laws, with exponents q = −1/4, p = 3/4 correspondingly. This set of exponents recovers the Toba's laws, and imposes the wave breaking exponent equal to 3. A varying wind direction can then drive spectral peak direction changes, leading to the occurrence of focusing/defocusing wave groups over localized areas where wave‐rays merge and cross. Significant (but finite) local variations of the energy are then expected under varying wind forcing. Propagating away from a stormy area, wave rays generally diverge, leading to dispersive swell systems. Examples of practical applications of this model are provided in (Kudryavtsev et al., 2021, companion paper).
On the Isotopic Composition of Cold Pools in Radiative‐Convective Equilibrium
Authors: Torri Giuseppe 
Published: March 2021

AbstractAlthough stable water isotopologues are important tools in the study of the climate system, some of the physical processes that affect them are still imperfectly constrained. In this work, I concentrate on cold pools, essential components of deep convective systems that are arguably one of the least understood features from the water isotopologue perspective. Using a combination of a Lagrangian and an Eulerian framework, I first focus on quantifying how different processes determine the initial water vapor isotopic composition of cold pools. By analyzing the precipitation‐driven downdrafts that give rise to cold pools, I determine that mixing with environmental air has an enriching effect. On the other hand, microphysical processes tend to deplete the downdraft in the initial stages, mostly in the free troposphere, and to enrich it in the final stages, when the downdraft is in the subcloud layer. Then, I consider what processes might influence the isotopic composition of cold pools during their propagation, and I find that surface latent heat fluxes play a much greater role than cold pool entrainment. Finally, I show how water isotopologues could be used to diagnose the origin of water vapor in cold pool moist patches.
Nonlinear Coupling Between Longwave Radiative Climate Feedbacks
Authors: Huang Han , Huang Yi 
Published: March 2021

AbstractThe radiative feedbacks of such climate variables as air temperature, water vapor, and clouds influence the energy budget of the climate system. Measuring the strength of each feedback is of critical importance for understanding the climate sensitivity and its spread in climate models. Most feedback analyses to‐date, such as those using the kernel method, have been based on a linear decomposition of the radiation budget and neglect the nonlinear effects between the feedbacks. In this work, we quantify the coupling effects between different longwave radiative feedbacks based on partial radiative perturbations using a radiative transfer model. Two climate change scenarios, the El niño‐Southern Oscillation (ENSO) and the quadrupling CO2 (4xCO2), are examined. We find that the coupling effect between water vapor and cloud is the strongest among all the coupling effects and can amount to 50% or greater of the univariate cloud feedback. This significant coupling effect results from the masking effect of the two feedbacks on each other and can be well explained by a simple analytic model.
Upscaling Reactive Transport and Clogging in Shale Microcracks by Deep Learning
Authors: Wang Ziyan , Battiato Ilenia 
Published: March 2021

AbstractFracture networks in shales exhibit multiscale features. A rock system may contain a few main fractures and thousands of microcracks, whose length and aperture are orders of magnitude smaller than the former. It is computationally prohibitive to resolve all the fractures explicitly for such multiscale fracture networks. One traditional approach is to model the small‐scale features (e.g., microcracks in shales) as an effective medium. Although this fracture‐matrix conceptualization significantly reduces the problem complexity, there are classes of physical processes that cannot be accurately upscaled by effective medium approximations, for example, microcrack clogging during mineral reactions. In this work, we employ deep learning in place of effective medium theory to upscale physical processes in small‐scale features. Specifically, we consider reactive transport in a fracture‐microcrack network where microcracks can be clogged by precipitation. A deep learning multiscale algorithm is developed, in which the microcracks are upscaled as a wall boundary condition of the main fractures. The wall boundary condition is constructed by recurrent neural networks, which take concentration histories as input and predict the solute transport from main fractures to microcracks. The deep learning multiscale algorithm is first employed in specific scenarios, then a general model is developed which can work under various conditions. The new approach is validated against fully resolved simulations and an analytical solution, providing a reliable and efficient solution for problems that cannot be upscaled by effective medium models.
Cytoplasmic DNA accumulation preferentially triggers cell death of myeloid leukemia cells by interacting with intracellular DNA sensing pathway
Authors: Baba Tomohisa , Yoshida Takeshi , Tanabe Yamato , Nishimura Tatsunori , Morishita Soji , Gotoh Noriko , Hirao Atsushi , Hanayama Rikinari , Mukaida Naofumi 
Published: March 2021

AbstractAccumulating evidence indicates the presence of cytoplasmic DNAs in various types of malignant cells, and its involvement in anti-cancer drug- or radiotherapy-mediated DNA damage response and replication stress. However, the pathophysiological roles of cytoplasmic DNAs in leukemias remain largely unknown. We observed that during hematopoietic stem cell transplantation (HSCT) in mouse myeloid leukemia models, double-stranded (ds)DNAs were constitutively secreted in the form of extracellular vesicles (EVs) from myeloid leukemia cells and were transferred to the donor cells to dampen their hematopoietic capabilities. Subsequent analysis of cytoplasmic DNA dynamics in leukemia cells revealed that autophagy regulated cytoplasmic dsDNA accumulation and subsequent redistribution into EVs. Moreover, accumulated cytoplasmic dsDNAs activated STING pathway, thereby reducing leukemia cell viability through reactive oxygen species (ROS) generation. Pharmaceutical inhibition of autophagosome formation induced cytoplasmic DNA accumulation, eventually triggering cytoplasmic DNA sensing pathways to exert cytotoxicity, preferentially in leukemia cells. Thus, manipulation of cytoplasmic dsDNA dynamics can be a novel and potent therapeutic strategy for myeloid leukemias.
The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis
Authors: Luo Xiaoqing , Zheng Enze , Wei Li , Zeng Han , Qin Hong , Zhang Xiaoyu , Liao Meng , Chen Lin , Zhao Lei , Ruan Xiong Z. , Yang Ping , Chen Yaxi 
Published: March 2021

AbstractMetabolic reprogramming is a new hallmark of cancer but it remains poorly defined in hepatocellular carcinogenesis (HCC). The fatty acid receptor CD36 is associated with both lipid and glucose metabolism in the liver. However, the role of CD36 in metabolic reprogramming in the progression of HCC still remains to be elucidated. In the present study, we found that CD36 is highly expressed in human HCC as compared with non-tumor hepatic tissue. CD36 overexpression promoted the proliferation, migration, invasion, and in vivo tumor growth of HCC cells, whereas silencing CD36 had the opposite effects. By analysis of cell metabolic phenotype, CD36 expression showed a positive association with extracellular acidification rate, a measure of glycolysis, instead of oxygen consumption rate. Further experiments verified that overexpression of CD36 resulted in increased glycolysis flux and lactic acid production. Mechanistically, CD36 induced mTOR-mediated oncogenic glycolysis via activation of Src/PI3K/AKT signaling axis. Pretreatment of HCC cells with PI3K/AKT/mTOR inhibitors largely blocked the tumor-promoting effect of CD36. Our findings suggest that CD36 exerts a stimulatory effect on HCC growth and metastasis, through mediating aerobic glycolysis by the Src/PI3K/AKT/mTOR signaling pathway.
CXCR4 promotes B cell viability by the cooperation of nuclear factor (erythroid-derived 2)-like 2 and hypoxia-inducible factor-1α under hypoxic conditions
Authors: Jang Ju-Won , Thuy Pham Xuan , Lee Jae-Wook , Moon Eun-Yi 
Published: March 2021

AbstractB cells that interact with T cells play a role in regulating the defense function by producing antibodies and inflammatory cytokines. C-X-C chemokine receptor type 4 (CXCR4) is a specific receptor for stromal cell-derived factor 1 (SDF-1) that controls various B cell functions. Here, we investigated whether CXCR4 regulates B cell viability by inducing hypoxia-inducible factor (HIF)-1α and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) under a hypoxic condition in WiL2-NS human B cells. Nrf2 and CXCR4 expressions increased significantly when WiL2-NS cells were incubated under a hypoxic condition. Interfering with CXCR4 expression using CXCR4-siRNA inhibited cell viability. CXCR4 expression also decreased after treatment with a HIF inhibitor under the hypoxic condition, leading to inhibited cell viability. Increased reactive oxygen species (ROS) levels and the expression of HIF-1α and Nrf2 decreased under the hypoxic condition following incubation with N-acetylcysteine, a ROS scavenger, which was associated with a decrease in CXCR4 expression. CXCR4 expression was augmented by overexpressing Nrf2 after transfecting the pcDNA3.1-Nrf2 plasmid. CXCR4 expression decreased and HIF-1α accumulation decreased when Nrf2 was inhibited by doxycycline in tet-shNrf2-expressed stable cells. Nrf2 or HIF-1α bound from −718 to −561 of the CXCR4 gene promoter as judged by a chromatin immunoprecipitation assay. Taken together, these data show that B cell viability under a hypoxic condition could be regulated by CXCR4 expression through binding of HIF-1α and Nrf2 to the CXCR4 gene promoter cooperatively. These results suggest that CXCR4 could be an additional therapeutic target to control B cells with roles at disease sites under hypoxic conditions.
Ceramides and sphingosine-1-phosphate mediate the distinct effects of M1/M2-macrophage infusion on liver recovery after hepatectomy
Authors: Sun Hang , Sun Shibo , Chen Gang , Xie Haorong , Yu Sheng , Lin Xinxin , Qian Jianping , Mao Cungui , Peng Hongxian , Chen Hao , Chen Xuefang , Li Yiyi , Liu Cuiting , Shi Junmin , Zhu Bili , Guo Linghong , Li Qingping , Huang Pengxiang , Wei Yiran , Huang Xixin , Liu Meiqi , Cui Zhonglin , Zhang Qifan , Zhou Jie , Li Chuanjiang , Wang Kai 
Published: March 2021

AbstractPost-hepatectomy liver dysfunction is a life-threatening morbidity that lacks efficient therapy. Bioactive lipids involved in macrophage polarization crucially regulate tissue injury and regeneration. Herein, we investigate the key bioactive lipids that mediate the cytotherapeutic potential of polarized-macrophage for post-hepatectomy liver dysfunction. Untargeted lipidomics identified elevation of ceramide (CER) metabolites as signature lipid species relevant to M1/M2 polarization in mouse bone-marrow-derived-macrophages (BMDMs). M1 BMDMs expressed a CER-generation-metabolic pattern, leading to elevation of CER; M2 BMDMs expressed a CER-breakdown-metabolic pattern, resulting in upregulation of sphingosine-1-phosphate (S1P). After infusing M1- or M2-polarized BMDMs into the mouse liver after hepatectomy, we found that M1-BMDM infusion increased M1 polarization and CER accumulation, resulting in exaggeration of hepatocyte apoptosis and liver dysfunction. Conversely, M2-BMDM infusion enhanced M2 polarization and S1P generation, leading to alleviation of liver dysfunction with improved hepatocyte proliferation. Treatment of exogenous CER and S1P or inhibition CER and S1P synthesis by siRNA targeting relevant enzymes further revealed that CER induced apoptosis while S1P promoted proliferation in post-hepatectomy primary hepatocytes. In conclusion, CER and S1P are uncovered as critical lipid mediators for M1- and M2-polarized BMDMs to promote injury and regeneration in the liver after hepatectomy, respectively. Notably, the upregulation of hepatic S1P induced by M2-BMDM infusion may have therapeutic potential for post-hepatectomy liver dysfunction.
Long non-coding RNA ZFAS1 is a major regulator of epithelial-mesenchymal transition through miR-200/ZEB1/E-cadherin, vimentin signaling in colon adenocarcinoma
Authors: O’Brien Stephen J. , Fiechter Casey , Burton James , Hallion Jacob , Paas Mason , Patel Ankur , Patel Ajay , Rochet Andre , Scheurlen Katharina , Gardner Sarah , Eichenberger Maurice , Sarojini Harshini , Srivastava Sudhir , Rai Shesh , Kalbfleisch Theodore , Polk Hiram C. , Galandiuk Susan 
Published: March 2021

AbstractColon adenocarcinoma is a common cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition is a major regulator of cancer metastasis, and increased understanding of this process is essential to improve patient outcomes. Long non-coding RNA (lncRNA) are important regulators of carcinogenesis. To identify lncRNAs associated with colon carcinogenesis, we performed an exploratory differential gene expression analysis comparing paired colon adenocarcinoma and normal colon epithelium using an RNA-sequencing data set. This analysis identified lncRNA ZFAS1 as significantly increased in colon cancer compared to normal colon epithelium. This finding was validated in an institutional cohort using laser capture microdissection. ZFAS1 was also found to be principally located in the cellular cytoplasm. ZFAS1 knockdown was associated with decreased cellular proliferation, migration, and invasion in two colon cancer cell lines (HT29 and SW480). MicroRNA-200b and microRNA-200c (miR-200b and miR-200c) are experimentally validated targets of ZFAS1, and this interaction was confirmed using reciprocal gene knockdown. ZFAS1 knockdown regulated ZEB1 gene expression and downstream targets E-cadherin and vimentin. Knockdown of miR-200b or miR-200c reversed the effect of ZFAS1 knockdown in the ZEB1/E-cadherin, vimentin signaling cascade, and the effects of cellular migration and invasion, but not cellular proliferation. ZFAS1 knockdown was also associated with decreased tumor growth in an in vivo mouse model. These results demonstrate the critical importance of ZFAS1 as a regulator of the miR-200/ZEB1/E-cadherin, vimentin signaling cascade.
Active carpets drive non-equilibrium diffusion and enhanced molecular fluxes
Authors: Guzmán-Lastra Francisca , Löwen Hartmut , Mathijssen Arnold J. T. M. 
Published: March 2021

AbstractBiological activity is often highly concentrated on surfaces, across the scales from molecular motors and ciliary arrays to sessile and motile organisms. These ‘active carpets’ locally inject energy into their surrounding fluid. Whereas Fick’s laws of diffusion are established near equilibrium, it is unclear how to solve non-equilibrium transport driven by such boundary-actuated fluctuations. Here, we derive the enhanced diffusivity of molecules or passive particles as a function of distance from an active carpet. Following Schnitzer’s telegraph model, we then cast these results into generalised Fick’s laws. Two archetypal problems are solved using these laws: First, considering sedimentation towards an active carpet, we find a self-cleaning effect where surface-driven fluctuations can repel particles. Second, considering diffusion from a source to an active sink, say nutrient capture by suspension feeders, we find a large molecular flux compared to thermal diffusion. Hence, our results could elucidate certain non-equilibrium properties of active coating materials and life at interfaces.
N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection
Authors: Shan Dandan , Johnson Joseph M. , Fernandes Syrena C. , Suib Hannah , Hwang Soyoon , Wuelfing Danica , Mendes Muriel , Holdridge Marcella , Burke Elaine M. , Beauregard Katie , Zhang Ying , Cleary Megan , Xu Samantha , Yao Xiao , Patel Purvish P. , Plavina Tatiana , Wilson David H. , Chang Lei , Kaiser Kim M. , Nattermann Jacob , Schmidt Susanne V. , Latz Eicke , Hrusovsky Kevin , Mattoon Dawn , Ball Andrew J. 
Published: March 2021

AbstractThe COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. There remains an ongoing need for high-performance SARS-CoV-2 tests which may be broadly deployed for infection monitoring. Here we report a highly sensitive single molecule array (Simoa) immunoassay in development for detection of SARS-CoV-2 nucleocapsid protein (N-protein) in venous and capillary blood and saliva. In all matrices in the studies conducted to date we observe >98% negative percent agreement and >90% positive percent agreement with molecular testing for days 1–7 in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals. N-protein load decreases as anti-SARS-CoV-2 spike-IgG increases, and N-protein levels correlate with RT-PCR Ct-values in saliva, and between matched saliva and capillary blood samples. This Simoa SARS-CoV-2 N-protein assay effectively detects SARS-CoV-2 infection via measurement of antigen levels in blood or saliva, using non-invasive, swab-independent collection methods, offering potential for at home and point of care sample collection.
Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome
Authors: Inak Gizem , Rybak-Wolf Agnieszka , Lisowski Pawel , Pentimalli Tancredi M. , Jüttner René , Glažar Petar , Uppal Karan , Bottani Emanuela , Brunetti Dario , Secker Christopher , Zink Annika , Meierhofer David , Henke Marie-Thérèse , Dey Monishita , Ciptasari Ummi , Mlody Barbara , Hahn Tobias , Berruezo-Llacuna Maria , Karaiskos Nikos , Di Virgilio Michela , Mayr Johannes A. , Wortmann Saskia B. , Priller Josef , Gotthardt Michael , Jones Dean P. , Mayatepek Ertan , Stenzel Werner , Diecke Sebastian , Kühn Ralf , Wanker Erich E. , Rajewsky Nikolaus , Schuelke Markus , Prigione Alessandro 
Published: March 2021

AbstractLeigh syndrome (LS) is a severe manifestation of mitochondrial disease in children and is currently incurable. The lack of effective models hampers our understanding of the mechanisms underlying the neuronal pathology of LS. Using patient-derived induced pluripotent stem cells and CRISPR/Cas9 engineering, we developed a human model of LS caused by mutations in the complex IV assembly gene SURF1. Single-cell RNA-sequencing and multi-omics analysis revealed compromised neuronal morphogenesis in mutant neural cultures and brain organoids. The defects emerged at the level of neural progenitor cells (NPCs), which retained a glycolytic proliferative state that failed to instruct neuronal morphogenesis. LS NPCs carrying mutations in the complex I gene NDUFS4 recapitulated morphogenesis defects. SURF1 gene augmentation and PGC1A induction via bezafibrate treatment supported the metabolic programming of LS NPCs, leading to restored neuronal morphogenesis. Our findings provide mechanistic insights and suggest potential interventional strategies for a rare mitochondrial disease.
Loss of bone morphogenetic protein-binding endothelial regulator causes insulin resistance
Authors: Mao Hua , Li Luge , Fan Qiying , Angelini Aude , Saha Pradip K. , Wu Huaizhu , Ballantyne Christie M. , Hartig Sean M. , Xie Liang , Pi Xinchun 
Published: March 2021

AbstractAccumulating evidence suggests that chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors impact metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here, we demonstrate that BMPER is a driver of insulin sensitivity. Both global and endothelial cell-specific inducible knockout of BMPER cause hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues in mice. BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that transports intracellular cholesterol. These results suggest that the endocrine function of the vascular endothelium maintains glucose homeostasis. Of potential translational significance, the delivery of BMPER recombinant protein or its overexpression alleviates insulin resistance and hyperglycemia in high-fat diet-fed mice and Leprdb/db (db/db) diabetic mice. We conclude that BMPER exhibits therapeutic potential for the treatment of diabetes.