72 research outputs found

    The significance of slab for structural response under travelling fires

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    The role of “travelling fires” is to ensure the robustness of structural design with large compartments under realistic fires, having a fire plume at the near-field, and a hot smoke layer preheating the ceiling at the farfield. Once the fire travels, the near-field has a leading edge representing the fire spread, and a trailing edge representing the burnout of the fuel. Though well understood by its definition, the mainstream of efforts on travelling fires for structural response is limited to 2D finite element modelling (FEM). This paper aims to identify the importance of slab inclusion with a 3D FEM structural model for steel-composite structures under travelling fires, with a special emphasis on the significance of ignoring the slab structural capacity contribution from a 2D simplified structural model. The role of fire protection scheme for 2D model against the 3D model on numerical predictions was also explored. It was found that the structural load path, and the potential structural failure mechanisms could be fundamentally different between the 3D model and the 2D model, i.e., with or without slabs. Although the 2D model tends to predict larger deflections (i.e. more conservative) than the 3D model, it could also significantly underestimate the large internal forces from the beams, which might overlook the connections failure under travelling fires. Further, due to the simplification of the 2D model omitting the significant stiffness contribution from the slab, the effect of the fire protection is likely to be amplified. It may be misleading for the performance-based structural fire design under different travelling fire scenarios. Hence, the 3D model is likely to be considered as necessary and feasible for structural fire analysis for travelling fires as a complement to the 2D model approach

    Identification of LncRNA Linc00513 Containing Lupus-Associated Genetic Variants as a Novel Regulator of Interferon Signaling Pathway

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    Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by augmented type I interferon signaling. High-throughput technologies have identified plenty of SLE susceptibility single-nucleotide polymorphisms (SNPs) yet the exact roles of most of them are still unknown. Functional studies are principally focused on SNPs in the coding regions, with limited attention paid to the SNPs in non-coding regions. Long non-coding RNAs (lncRNAs) are important players in shaping the immune response and show relationship to autoimmune diseases. In order to reveal the role of SNPs located near SLE related lncRNAs, we performed a transcriptome profiling of SLE patients and identified linc00513 as a significantly over expressed lncRNA containing functional SLE susceptibility loci in the promoter region. The risk-associated G allele of rs205764 and A allele of rs547311 enhanced linc00513 promoter activity and related to increased expression of linc00513 in SLE. We also identified linc00513 to be a novel positive regulator of type I interferon pathway by promoting the phosphorylation of STAT1 and STAT2. Elevated linc00513 expression positively correlated with IFN score in SLE patients. Linc00513 expression was higher in active disease patients than those inactive ones. In conclusion, our data identify two functional promoter variants of linc00513 that contribute to increased level of linc00513 and confer susceptibility on SLE. The study provides new insights into the genetics of SLE and extends the role of lncRNAs in the pathogenesis of SLE

    Identification of Renal Long Non-coding RNA RP11-2B6.2 as a Positive Regulator of Type I Interferon Signaling Pathway in Lupus Nephritis

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    Objective: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). Type I interferon (IFN-I) is associated with the pathogenesis of LN. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of SLE, however, the roles of lncRNAs in LN are still poorly understood. Here, we identified and investigated the function of LN-associated lncRNA RP11-2B6.2 in regulating IFN-I signaling pathway.Methods: RNA sequencing was used to analyze the expression of lncRNAs in kidney biopsies from LN patients and controls. Antisense oligonucleotides and CRISPRi system or overexpression plasmids and CRISPRa system were used to perform loss or gain of function experiments. In situ hybridization, imaging flow cytometry, dual-luciferase reporter assay, and ATAC sequencing were used to study the functions of lncRNA RP11-2B6.2. RT-qPCR, ELISA, and western blotting were done to detect RNA and protein levels of specific genes.Results: Elevated lncRNA RP11-2B6.2 was observed in kidney biopsies from LN patients and positively correlated with disease activity and IFN scores. Knockdown of lncRNA RP11-2B6.2 in renal cells inhibited the expression of IFN stimulated genes (ISGs), while overexpression of lncRNA RP11-2B6.2 enhanced ISG expression. Knockdown of LncRNA RP11-2B6.2 inhibited the phosphorylation of JAK1, TYK2, and STAT1 in IFN-I pathway, while promoted the chromatin accessibility and the transcription of SOCS1.Conclusion: The expression of lncRNAs is abnormal in the kidney of LN. LncRNA RP11-2B6.2 is a novel positive regulator of IFN-I pathway through epigenetic inhibition of SOCS1, which provides a new therapeutic target to alleviate over-activated IFN-I signaling in LN

    Potential of Core-Collapse Supernova Neutrino Detection at JUNO

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    JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

    Detection of the Diffuse Supernova Neutrino Background with JUNO

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    As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

    Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

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    Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30MM_{\odot} for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

    Relationship between patient-perceived quality of primary care and self-reported hospital utilisation in China: A cross-sectional study

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    AbstractBackground Reducing avoidable hospital admissions is a global healthcare priority, with optimal primary care recognised as pivotal for achieving this objective. However, in developing systems like China, where primary care is evolving without compulsory gatekeeping, the relationship between patient-perceived primary care quality and hospital utilisation remains underexplored.Objectives This study aimed to explore the association between patient-perceived primary care quality and self-reported hospital utilisation in China.Methods Data were collected from 16 primary care settings. Patient-perceived quality of primary care was measured using the Assessment Survey of Primary Care scale across six domains (first-contact care, continuity, comprehensiveness, accessibility, coordination, and patient-centredness). Hospital utilisation included patient self-reported outpatient visits, hospital admissions, and emergency department (ED) visits in the last six months. Logistic regression analyses were examined associations between self-reported hospital utilisation and perceived primary care quality adjusted for potential confounders.Results Of 1,185 patients recruited, 398 (33.6%) reported hospital utilisation. Logistic regression analyses showed that higher total scores for patient-perceived quality of primary care were associated with decreased odds of hospital utilisation (adjusted odds ratio(AOR): 0.417, 95% confidence interval (CI): 0.308–0.565), outpatient visits (AOR: 0.394, 95% CI: 0.275–0.566) and hospital admissions (AOR: 0.496, 95% CI: 0.276–0.891). However, continuity of care was positively associated with ED visits (AOR: 2.252, 95% CI: 1.051–4.825).Conclusion Enhanced patient-perceived quality of primary care in China is associated with a reduction in self-reported overall hospital utilisation, including outpatient visits and hospital admissions. However, better continuity of care may be associated with increased ED visits. Further research is warranted for precise insights and validation of these findings

    Additional file 1: of T-bet+CD11c+ B cells are critical for antichromatin immunoglobulin G production in the development of lupus

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    T-bet+ CD11c+ B cells are critical for antichromatin immunoglobulin G production in the development of lupus. Figure S1. The fraction of T-bet and CD11c positive population was increased in CD138+ plasma cells. Figure S2. Correlation between the percentage of T-bet+ CD11c+ CD19+ B cells and the titers of anti-ANA antibodies (A), anti-dsDNA antibodies (B) from 22 SLE patients. Figure S3. IFNγ is required for T-bet+ CD11c+ B cell differentiation and activation. 5 × 107 splenocytes from Bm12 mice or B6 mice cells were injected intraperitoneally into B6 mice (n = 5). (PDF 361 kb
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