Modeling method of failure dependent system based on time varying copula function

This paper aims at solving the dynamic correlation of the complex dependence system with multiple failures. A correlation model and parameter estimation method based on time-varying copula function are proposed to solve the joint distribution between the interaction mechanism. In particular, three types of definition method for the time-varying copulas’ parameters are introduced. Finally, a comparative study and applicability analysis are performed to validate our proposed method

MuLTI: Efficient Video-and-Language Understanding with MultiWay-Sampler and Multiple Choice Modeling

Video-and-language understanding has a variety of applications in the industry, such as video question answering, text-video retrieval and multi-label classification. Existing video-and-language understanding methods generally adopt heavy multi-modal encoders and feature fusion modules, which consume large amounts of GPU memory. Especially, they have difficulty dealing with dense video frames or long text that are prevalent in industrial applications. In this paper, we propose MuLTI, a highly accurate and memory-efficient video-and-language understanding model that achieves efficient and effective feature fusion through feature sampling and attention modules. Therefore, MuLTI can handle longer sequences with limited GPU memory. Then, we introduce an attention-based adapter to the encoders, which finetunes the shallow features to improve the model's performance with low GPU memory consumption. Finally, to further improve the model's performance, we introduce a new pretraining task named Multiple Choice Modeling to bridge the task gap between pretraining and downstream tasks and enhance the model's ability to align the video and the text. Benefiting from the efficient feature fusion module, the attention-based adapter and the new pretraining task, MuLTI achieves state-of-the-art performance on multiple datasets. Implementation and pretrained models will be released

Double-zero-event studies matter: A re-evaluation of physical distancing, face masks, and eye protection for preventing person-to-person transmission of COVID-19 and its policy impact

In a recent timely systematic review, Chu et al. [1] assessed the effectiveness of face masks, eye protection, and physical distancing for preventing COVID-19. Because the sample sizes are not large, especially in some studies of COVID-19, this review contains a considerable number of studies with zero counts of infection events, creating challenges in estimating effect sizes. If zero counts appear in both groups, this double-zero-event study (DZS) is omitted from the analyses, as implied in the forest plots in Chu et al. [1] Specifically, at least 9 out of 44 studies in this review are DZS with 1784 subjects. An omission of information about the rare outcome in DZS or artificial correction of the zero counts could impact the conclusions. [2], [3], [4], [5].This research was supported in part by the U.S. National Institutes of Health/National Library of Medicine grant R01 LM012982. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

Metformin downregulates PD-L1 expression in esophageal squamous cell catrcinoma by inhibiting IL-6 signaling pathway

Purpose: To characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response. Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the correlations between IL-6 and prognosis and between IL-6 and PD-L1 gene expression in esophageal cancer. Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression. Additionally, T cell function was assessed in a coculture system containing ESCC cells and peripheral blood mononuclear cells (PBMCs) treated with metformin or IL-6. In an Results: The TCGA esophageal cancer data showed that IL-6 expression was positively correlated with PD-L1 expression and that patients with high IL-6 expression had a significantly lower overall survival rate than patients with low IL-6 expression. PD-L1 expression in ESCC cell lines was significantly inhibited by metformin Conclusions: Metformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response

SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense

Abstract Excess in mitochondrial reactive oxygen species (ROS) is considered as a major cause of cellular oxidative stress. NADPH, the main intracellular reductant, has a key role in keeping glutathione in its reduced form GSH, which scavenges ROS and thus protects the cell from oxidative damage. Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose‐6‐phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH‐producing enzymes. Moreover, we show that knockdown or knockout of SIRT5 leads to high levels of cellular ROS. SIRT5 inactivation leads to the inhibition of IDH2 and G6PD, thereby decreasing NADPH production, lowering GSH, impairing the ability to scavenge ROS, and increasing cellular susceptibility to oxidative stress. Our study uncovers a SIRT5‐dependent mechanism that regulates cellular NADPH homeostasis and redox potential by promoting IDH2 desuccinylation and G6PD deglutarylation

Tumor Mutation Burden Predicts Relapse in Papillary Thyroid Carcinoma With Changes in Genes and Immune Microenvironment

BackgroundThe risk factors of papillary thyroid carcinoma (PTC) recurrence are meaningful for patients and clinicians. Tumor mutation burden (TMB) has been a biomarker for the effectiveness of immune checkpoint inhibitor (ICI) and prognosis in cancer. However, the role of TMB and its latent significance with immune cell infiltration in PTC are still unclear. Herein, we aimed to explore the effect of TMB on PTC prognosis.Material and MethodsRNA-seq and DNA-seq datasets of PTC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The Gene Ontology (GO) and gene set enrichment analysis (GSEA 4.0.1) were applied further to explore potential differences in PTC patients’ biological functions. The differentially expressed genes (DEGs) and immune microenvironment between the high and low TMB groups were determined.ResultsTMB had the highest AUC score than other clinical indicators in ROC analysis on recurrence-free survival, and a higher TMB score was related to a worse prognosis. Further, GSEA showed a higher level of oxidative phosphorylation (OXPHOS) in the high TMB group, and four genes correlated with recurrence-free survival rate were identified. The abundance of CD8+ T cells and M1 macrophages in the high TMB group was significantly lower than that in the low TMB group.ConclusionsOur study found that TMB was a better predictor variable at evaluating the risk of PTC recurrence. Moreover, TMB-related genes conferred dramatically correlated prognosis, which was worth exploring in guiding postoperative follow-up and predicting recurrence for PTC patients

A dual-target molecular mechanism of pyrethrum repellency against mosquitoes

Pyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents. While the molecular mechanisms of its insecticidal action are known, the molecular basis of pyrethrum repellency remains a mystery. In this study, we find that the principal components of pyrethrum, pyrethrins, and a minor component, (E)-β-farnesene (EBF), each activate a specific type of olfactory receptor neurons in Aedes aegypti mosquitoes. We identify Ae. aegypti odorant receptor 31 (AaOr31) as a cognate Or for EBF and find that Or31-mediated repellency is significantly synergized by pyrethrin-induced activation of voltage-gated sodium channels. Thus, pyrethrum exerts spatial repellency through a novel, dual-target mechanism. Elucidation of this two-target mechanism may have potential implications in the design and development of a new generation of synthetic repellents against major mosquito vectors of infectious diseases