MicroRNA-146a-5p Mediates High Glucose-Induced Endothelial Inflammation via Targeting Interleukin-1 Receptor-Associated Kinase 1 Expression

Background and Aims: Interleukin-1 receptor-associated kinase-1 (IRAK-1) is critical for mediating toll-like receptor and interleukin-1 receptor signaling. In this study, we have examined whether IRAK-1 expression is altered in high glucose (HG)-stimulated human aortic endothelial cells (HAECs), and whether microRNAs (miRs) target IRAK-1 to regulate HG-induced endothelial inflammation.Methods: HAECs were treated with HG for 24 and 48 h. Real-time PCR, Western blot, monocyte adhesion assay, bioinformatics analysis, TaqMan® arrays, microRNA mimic or inhibitor transfection, luciferase reporter assay and siRNA IRAK-1 transfection were performed. The aortic tissues from db/db type 2 diabetic mice were examined by immunohistochemistry staining.Results: HG time-dependently increased IRAK-1 mRNA and protein levels in HAECs, and was associated with increased VCAM-1/ICAM-1 gene expression and monocyte adhesion. Bioinformatic analysis, TaqMan® arrays, and real-time PCR were used to confirm that miR-146a-5p, miR-339-5p, and miR-874-3p were significantly downregulated in HG-stimulated HAECs, suggesting impaired feedback restraints on HG-induced endothelial inflammation via IRAK-1. However, only miR-146a-5p mimic transfection reduced the HG-induced upregulation of IRAK-1 expression, VCAM-1/ICAM-1 expression, and monocyte adhesion. Additionally, IRAK-1 depletion reduced HG-induced VCAM-1/ICAM-1 gene expression, and monocyte adhesion, indicating that HG-induced endothelial inflammation was mediated partially through IRAK-1. In vivo, intravenous injections of miR-146a-5p mimic prevented endothelial IRAK-1 and ICAM-1 expression in db/db mice.Conclusion: These results suggest that miR-146a-5p is involved in the regulation of HG-induced endothelial inflammation via modulation of IRAK-1; indicating that miR-146a-5p may be a novel target for the treatment of diabetic vascular complications

Direct determination of band-gap renormalization in degenerately doped ultrawide band gap β-Ga_{2}O_{3} semiconductor

Ga2O3 is emerging as a promising wide band-gap semiconductor for high-power electronics and deep ultraviolet optoelectronics. It is highly desirable to dope it with controllable carrier concentrations for different device applications. This work reports a combined photoemission spectroscopy and theoretical calculation study on the electronic structure of Si doped Ga_{2}O_{3} films with carrier concentration varying from 4.6×10^{18} cm^{−3} to 2.6×10^{20} cm^{−3}. Hard x-ray photoelectron spectroscopy was used to directly measure the widening of the band gap as a result of occupation of conduction band and band-gap renormalization associated with many-body interactions. A large band-gap renormalization of 0.3 eV was directly observed in heavily doped Ga_{2}O_{3}. Supplemented with hybrid density functional theory calculations, we demonstrated that the band-gap renormalization results from the decrease in energy of the conduction band edge driven by the mutual electrostatic interaction between added electrons. Moreover, our work reveals that Si is a superior dopant over Ge and Sn, because Si 3s forms a resonant donor state above the conduction band minimum, leaving the host conduction band mostly unperturbed and a high mobility is maintained though the doping level is high. Insights of the present work have significant implications in doping optimization of Ga_{2}O_{3} and realization of optoelectronic devices

Deep UV transparent conductive oxide thin films realized through degenerately doped wide-bandgap gallium oxide

Deep UV transparent thin films have recently attracted considerable attention owing to their potential in UV and organic-based optoelectronics. Here, we report the achievement of a deep UV transparent and highly conductive thin film based on Si-doped Ga_{2}O_{3} (SGO) with high conductivity of 2500 S/cm. The SGO thin films exhibit high transparency over a wide spectrum ranging from visible light to deep UV wavelength and, meanwhile, have a very low work-function of approximately 3.2 eV. A combination of photoemission spectroscopy and theoretical studies reveals that the delocalized conduction band derived from Ga 4s orbitals is responsible for the Ga_{2}O_{3} films’ high conductivity. Furthermore, Si is shown to act as an efficient shallow donor, yielding high mobility up to approximately 60 cm^{2}/Vs. The superior optoelectronic properties of SGO films make it a promising material for use as electrodes in high-power electronics and deep UV and organic-based optoelectronic devices

Mean structure and fluctuations of the Kuroshio east of Taiwan from in situ and remote observations

Author Posting. © The Oceanography Society, 2015. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 28, no. 4 (2015): 74–83, doi:10.5670/oceanog.2015.83.The Kuroshio is important to climate, weather prediction, and fishery management along the northeast coast of Asia because it transports tremendous heat, salt, and energy from east of the Philippines to waters southeast of Japan. In the middle of its journey northward, the Kuroshio’s velocity mean and its variability east of Taiwan crucially affect its downstream variability. To improve understanding of the Kuroshio there, multiple platforms were used to collect intensive observations off Taiwan during the three-year Observations of the Kuroshio Transports and their Variability (OKTV) program (2012–2015). Mean Kuroshio velocity transects show two velocity maxima southeast of Taiwan, with the primary velocity core on the onshore side of the Kuroshio exhibiting a mean maximum velocity of ~1.2 m s–1. The two cores then merge and move at a single velocity maximum of ~1 m s–1 east of Taiwan. Standard deviations of both the directly measured poleward (v) and zonal (u) velocities are ~0.4 m s–1 in the Kuroshio main stream. Water mass exchange in the Kuroshio east of Taiwan was found to be complicated, as it includes water of Kuroshio origin, South China Sea Water, and West Philippine Sea Water, and it vitally affects heat, salt, and nutrient inputs to the East China Sea. Impinging eddies and typhoons are two of the principal causes of variability in the Kuroshio. This study’s models are more consistent with the observed Kuroshio than with high-frequency radar measurements.This study was sponsored by the Ministry of Science and Technology (MOST) of the ROC (Taiwan) under grants NSC 101-2611-M-002-018-MY3, NSC 101-2611- M-019-002, NSC 102-2611-M-002-017, NSC 102-2611- M-019-012, MOST 103-2611-M-002-014, and MOST 103-2611-M-002-018. MA was sponsored by the US Office of Naval Research under grant N00014- 12-1-0445. YHT was supported by NSF Earth System Model (EaSM) Grant 1419292

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN