163 research outputs found

    Two positive solutions for second-order quasilinear differential equation boundary value problems with sign changing nonlinearities

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    AbstractIn this paper, the second order quasilinear differential equation (Φ(y′))′+q(t)f(t,y)=0,0<t<1 subject to Dirichlet boundary conditions and mixed boundary conditions is studied, where f is allowed to change sign, Φ(v)=|v|p−2v,p>1. We show the existence of at least two positive solutions by using a new fixed point theorem in cones

    ELSA: Efficient Label Shift Adaptation through the Lens of Semiparametric Models

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    We study the domain adaptation problem with label shift in this work. Under the label shift context, the marginal distribution of the label varies across the training and testing datasets, while the conditional distribution of features given the label is the same. Traditional label shift adaptation methods either suffer from large estimation errors or require cumbersome post-prediction calibrations. To address these issues, we first propose a moment-matching framework for adapting the label shift based on the geometry of the influence function. Under such a framework, we propose a novel method named \underline{E}fficient \underline{L}abel \underline{S}hift \underline{A}daptation (ELSA), in which the adaptation weights can be estimated by solving linear systems. Theoretically, the ELSA estimator is n\sqrt{n}-consistent (nn is the sample size of the source data) and asymptotically normal. Empirically, we show that ELSA can achieve state-of-the-art estimation performances without post-prediction calibrations, thus, gaining computational efficiency

    Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus.

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    Nucleus pulposus (NP) cells reside in a physiologically hyperosmotic environment within the intervertebral disc. TonEBP/NFAT5 is an osmo-sensitive transcription factor that controls expression of genes critical for cell survival under hyperosmotic conditions. A recent report on NP and studies of other cell types have shown that hyperosmolarity triggers autophagy. However, little is known whether such autophagy induction occurs through TonEBP. The goal of this study was to investigate the role of TonEBP in hyperosmolarity-dependent autophagy in NP. Loss-of-function studies showed that autophagy in NP cells was not TonEBP-dependent; hyperosmolarity did not upregulate autophagy as previously reported. NP tissue of haploinsufficient TonEBP mice showed normal pattern of LC3 staining. NP cells did not increase LC3-II or LC3-positive puncta under hyperosmotic conditions. Bafilomycin-A1 treatment and tandem mCherry-EGFP-LC3B reporter transfection demonstrated that the autophagic flux was unaffected by hyperosmolarity. Even under serum-free conditions, NP cells did not induce autophagy with increasing osmolarity. Hyperosmolarity did not change the phosphorylation of ULK1 by mTOR and AMPK. An ex vivo disc organ culture study supported that extracellular hyperosmolarity plays no role in promoting autophagy in the NP. We conclude that hyperosmolarity does not play a role in autophagy induction in NP cells

    Three-Dimensional Distribution of Turbulent Mixing in the South China Sea*

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    A three-dimensional distribution of turbulent mixing in the South China Sea (SCS) is obtained for the first time, using the Gregg–Henyey–Polzin parameterization and hydrographic observations from 2005 to 2012. Results indicate that turbulent mixing generally increases with depth in the SCS, reaching the order of 10[superscript −2] m[superscript 2] s[superscript −1] at depth. In the horizontal direction, turbulence is more active in the northern SCS than in the south and is more active in the east than the west. Two mixing “hotspots” are identified in the bottom water of the Luzon Strait and Zhongsha Island Chain area, where diapycnal diffusivity values are around 3 × 10[superscript −2] m[superscript 2] s[superscript −1]. Potential mechanisms responsible for these spatial patterns are discussed, which include internal tide, bottom bathymetry, and near-inertial energy

    Novel insights into the Thaumarchaeota in the deepest oceans: their metabolism and potential adaptation mechanisms

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    Background: Marine Group I (MGI) Thaumarchaeota, which play key roles in the global biogeochemical cycling of nitrogen and carbon (ammonia oxidizers), thrive in the aphotic deep sea with massive populations. Recent studies have revealed that MGI Thaumarchaeota were present in the deepest part of oceans - the hadal zone (depth > 6,000 m, consisting almost entirely of trenches), with the predominant phylotype being distinct from that in the “shallower” deep sea. However, little is known about the metabolism and distribution of these ammonia oxidizers in the hadal water. Results: In this study, metagenomic data were obtained from 0-10,500 m deep seawater samples from the Mariana Trench. The distribution patterns of Thaumarchaeota derived from metagenomics and 16S rRNA gene sequencing were in line with that reported in previous studies: abundance of Thaumarchaeota peaked in bathypelagic zone (depth 1,000 – 4,000 m) and the predominant clade shifted in the hadal zone. Several metagenome-assembled thaumarchaeotal genomes were recovered, including a near-complete one representing the dominant hadal phylotype of MGI. Using comparative genomics we predict that unexpected genes involved in bioenergetics, including two distinct ATP synthase genes (predicted to be coupled with H+ and Na+ respectively), and genes horizontally transferred from other extremophiles, such as those encoding putative di-myo-inositol-phosphate (DIP) synthases, might significantly contribute to the success of this hadal clade under the extreme condition. We also found that hadal MGI have the genetic potential to import a far higher range of organic compounds than their shallower water counterparts. Despite this trait, hadal MDI ammonia oxidation and carbon fixation genes are highly transcribed providing evidence they are likely autotrophic, contributing to the primary production in the aphotic deep sea. Conclusions: Our study reveals potentially novel adaptation mechanisms of deep-sea thaumarchaeotal clades and suggests key functions of deep-sea Thaumarchaeota in carbon and nitrogen cycling

    Observed 3D Structure, Generation, and Dissipation of Oceanic Mesoscale Eddies in the South China Sea

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    Oceanic mesoscale eddies with horizontal scales of 50–300 km are the most energetic form of flows in the ocean. They are the oceanic analogues of atmospheric storms and are effective transporters of heat, nutrients, dissolved carbon, and other biochemical materials in the ocean. Although oceanic eddies have been ubiquitously observed in the world oceans since 1960s, our understanding of their three-dimensional (3D) structure, generation, and dissipation remains fragmentary due to lack of systematic full water-depth measurements. To bridge this knowledge gap, we designed and conducted a multi-months field campaign, called the South China Sea Mesoscale Eddy Experiment (S-MEE), in the northern South China Sea in 2013/2014. The S-MEE for the first time captured full-depth 3D structures of an anticyclonic and cyclonic eddy pair, which are characterized by a distinct vertical tilt of their axes. By observing the eddy evolution at an upstream versus downstream location and conducting an eddy energy budget analysis, the authors further proposed that generation of submesoscale motions most likely constitutes the dominant dissipation mechanism for the observed eddies

    Two positive solutions for second-order quasilinear differential equation boundary value problems with sign changing nonlinearities

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    AbstractIn this paper, the second order quasilinear differential equation (Φ(y′))′+q(t)f(t,y)=0,0<t<1 subject to Dirichlet boundary conditions and mixed boundary conditions is studied, where f is allowed to change sign, Φ(v)=|v|p−2v,p>1. We show the existence of at least two positive solutions by using a new fixed point theorem in cones

    RNAi-mediated knockdown of cyclooxygenase2 inhibits the growth, invasion and migration of SaOS2 human osteosarcoma cells: a case control study

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    <p>Abstract</p> <p>Background</p> <p>Cyclooxygenase2 (COX-2), one isoform of cyclooxygenase proinflammatory enzymes, is responsible for tumor development, invasion and metastasis. Due to its role and frequent overexpression in a variety of human malignancies, including osteosarcoma, COX-2 has received considerable attention. However, the function of COX-2 in the pathogenesis of cancer is not well understood. We examined the role of COX-2 in osteosarcoma.</p> <p>Methods</p> <p>We employed lentivirus mediated-RNA interference technology to knockdown endogenous gene COX-2 expression in human osteosarcoma cells (SaOS2) and analyzed the phenotypical changes. The effect of COX-2 treatment on the proliferation, cell cycle, invasion and migration of the SaOS2 cells were assessed using the MTT, flow cytometry, invasion and migration assays, respectively. COX-2, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) mRNA and protein expression were detected by RT-PCR and western blotting.</p> <p>Results</p> <p>Our results indicate that a decrease of COX-2 expression in human osteosarcoma cells significantly inhibited the growth, decreased the invasion and migration ability of SaOS2 cells. In addition, it also reduced VEGF, EGF and bFGF mRNA and protein expression.</p> <p>Conclusions</p> <p>The COX-2 signaling pathway may provide a novel therapeutic target for the treatment of human osteosarcoma.</p

    MAPK8 and CAPN1 as potential biomarkers of intervertebral disc degeneration overlapping immune infiltration, autophagy, and ceRNA

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    BackgroundIntervertebral disc degeneration (IDD) is one of the most common health problems in the elderly and a major causative factor in low back pain (LBP). An increasing number of studies have shown that IDD is closely associated with autophagy and immune dysregulation. Therefore, the aim of this study was to identify autophagy-related biomarkers and gene regulatory networks in IDD and potential therapeutic targets.MethodsWe obtained the gene expression profiles of IDD by downloading the datasets GSE176205 and GSE167931 from the Gene Expression Omnibus (GEO) public database. Subsequently, differentially expressed genes (DEGs) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene ontology (GO), and gene set enrichment analysis (GSEA) were performed to explore the biological functions of DEGs. Differentially expressed autophagy-related genes (DE-ARGs) were then crossed with the autophagy gene database. The hub genes were screened using the DE-ARGs protein–protein interaction (PPI) network. The correlation between the hub genes and immune infiltration and the construction of the gene regulatory network of the hub genes were confirmed. Finally, quantitative PCR (qPCR) was used to validate the correlation of hub genes in a rat IDD model.ResultsWe obtained 636 DEGs enriched in the autophagy pathway. Our analysis revealed 30 DE-ARGs, of which six hub genes (MAPK8, CTSB, PRKCD, SNCA, CAPN1, and EGFR) were identified using the MCODE plugin. Immune cell infiltration analysis revealed that there was an increased proportion of CD8+ T cells and M0 macrophages in IDD, whereas CD4+ memory T cells, neutrophils, resting dendritic cells, follicular helper T cells, and monocytes were much less abundant. Subsequently, the competitive endogenous RNA (ceRNA) network was constructed using 15 long non-coding RNAs (lncRNAs) and 21 microRNAs (miRNAs). In quantitative PCR (qPCR) validation, two hub genes, MAPK8 and CAPN1, were shown to be consistent with the bioinformatic analysis results.ConclusionOur study identified MAPK8 and CAPN1 as key biomarkers of IDD. These key hub genes may be potential therapeutic targets for IDD
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