Search

Addition of a small amount of La and Co enhances the stabilization of supercooled liquid and glass-forming ability (GFA) of an Al 85 Ni 7 Er 8 metallic glass. The Al 85 Ni 5 Co 2 Er 6 La 2 alloy exhibits large supercooled liquid region of 40 K, high GFA with a critical thickness of 450 μm, and the viscosities on the order of 10 7 −10 9 Pa s in the supercooled liquid state. The Al-based glassy nano-scale patterns were formed by imprinting, indicating its good thermoplastic formability. The possible mechanism for the improvement of the supercooled liquid stability of the Al Ni Er alloy by addition of La and Co elements was discussed in terms of the crystallization behavior. [ABSTRACT FROM AUTHOR]

Background: White blood cells have been shown in animal studies to play a central role in the pathogenesis of diabetic retinopathy. Lymphoblastoid cells are immortalized EBV-transformed primary B-cell leukocytes that have been extensively used as a model for conditions in which white blood cells play a primary role. The purpose of this study was to investigate whether lymphoblastoid cell lines, by retaining many of the key features of primary leukocytes, can be induced with glucose to demonstrate relevant biological responses to those found in diabetic retinopathy. Methods: Lymphoblastoid cell lines were obtained from twenty-three human subjects. Differences between high and standard glucose conditions were assessed for expression, endothelial adhesion, and reactive oxygen species. Results: Collectively, stimulation of the lymphoblastoid cell lines with high glucose demonstrated corresponding changes on molecular, cellular and functional levels. Lymphoblastoid cell lines up-regulated expression of a panel of genes associated with the leukocyte-mediated inflammation found in diabetic retinopathy that include: a cytokine (IL-1B fold change = 2.11, p-value = 0.02), an enzyme (PKCB fold change = 2.30, p-value = 0.01), transcription factors (NFKB-p50 fold change = 2.05, p-value = 0.01), (NFKB-p65 fold change = 2.82, p-value = 0.003), and an adhesion molecule (CD18 fold change = 2.59, 0.02). Protein expression of CD18 was also increased (p-value = 2.14x10-5). The lymphoblastoid cell lines demonstrated increased adhesiveness to endothelial cells (p = 1.28x10-5). Reactive oxygen species were increased (p = 2.56x10-6). Significant inter-individual variation among the lymphoblastoid cell lines in these responses was evident (F = 18.70, p < 0.0001). Conclusions: Exposure of lymphoblastoid cell lines derived from different human subjects to high glucose demonstrated differential and heterogeneous gene expression, adhesion, and cellular effects that recapitulated features found in the diabetic state. Lymphoblastoid cells may represent a useful tool to guide an individualized understanding of the development and potential treatment of diabetic complications like retinopathy. [ABSTRACT FROM AUTHOR]

Detachable pipe joints are an important component of aviation hydraulic systems, and their sealing performance is related to the safety and reliability of the entire machine. This paper focuses on the impact of assembly deviation and repeated assembly on the sealing performance of 35 MPa aviation pipe joints. The sealing performance of pipe joints was quantitatively evaluated using the sealing contact strength theory, and the influence of assembly deviation on sealing performance was studied using the finite element method. Designed a repeated tightening test device for pipe joints and conducted repeated tightening tests. A method for analyzing the initial loss of axial force, usage loss, and friction torque during repeated tightening of pipe joints has been established. Finally, combining experimental data and simulation calculations, the influence of repeated tightening on the sealing contact strength was analyzed. This study provides an analysis method and influencing law for the sealing performance of 35 MPa level detachable aviation pipe joints under assembly deviation and repeated assembly. The research content can provide theoretical guidance for the assembly process design of pipe joints. • Quantitatively assessed the effect of assembly deviations on the sealing performance of pipe fittings • Designed a repeated tightening test device for pipe joints and conducted repeated tightening tests. • The initial axial force loss, loss of use and friction torque of pipe joints during repeated assembly were evaluated. • The influence laws of assembly deviation and repeated assembly on the sealing performance of pipe joints were obtained. • The research content can provide theoretical guidance for the assembly process design of pipe joints. [ABSTRACT FROM AUTHOR]

Axial extrusion-connection technology is one of the important connection technologies for hydraulic piping systems, with high sealing performance and mechanical strength. In this paper, the finite-element-modeling method is used to simulate the experimental process of the connection strength of the axial extrusion joint. The generation mechanism and calculation method of the connection strength are analyzed. To optimize the joint strength, orthogonal testing and grey correlation analysis are used to analyze the influencing factors of joint strength. The key factors affecting joint strength are obtained as the friction coefficient μ 1 , μ 2 between joint components and the groove angle θ 1 of the fittings body. The back-propagation (BP) neural-network algorithm is used to establish the connection-strength model of the joint and the genetic algorithm is used to optimize it. The optimal connection strength is 8.237 kN and the optimal combination of influencing factors is 0.2, 0.4 and 76.8°. Compared with the prediction results of the neural-network genetic algorithm, the relative error of the finite-element results is 3.9%, indicating that the method has high accuracy. The results show that the extrusion-based joining process offers significant advantages in the manufacture of high-strength titanium tubular joints. [ABSTRACT FROM AUTHOR]

There is an urgent need for antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We screened a library of 1900 clinically safe drugs against OC43, a human beta coronavirus that causes the common cold, and evaluated the top hits against SARS-CoV-2. Twenty drugs significantly inhibited replication of both viruses in cultured human cells. Eight of these drugs inhibited the activity of the SARS-CoV-2 main protease, 3CLpro, with the most potent being masitinib, an orally bioavailable tyrosine kinase inhibitor. X-ray crystallography and biochemistry show that masitinib acts as a competitive inhibitor of 3CLpro. Mice infected with SARS-CoV-2 and then treated with masitinib showed >200-fold reduction in viral titers in the lungs and nose, as well as reduced lung inflammation. Masitinib was also effective in vitro against all tested variants of concern (B.1.1.7, B.1.351, and P.1). [ABSTRACT FROM AUTHOR]

Objective: To determine the genetic contribution to leukocyte endothelial adhesion. Methods: Leukocyte endothelial adhesion was assessed through a novel cell-based assay using human lymphoblastoid cell lines. A high-throughput screening method was developed to evaluate the inter-individual variability in leukocyte endothelial adhesion using lymphoblastoid cell lines derived from different donors. To assess heritability, ninety-two lymphoblastoid cell lines derived from twenty-three monozygotic twin pairs and twenty-three sibling pairs were compared. These lymphoblastoid cell lines were plated with the endothelial cell line EA.hy926 and labeled with Calcein AM dye. Fluorescence was assessed to determine endothelial cell adhesion to each lymphoblastoid cell line. Intra-pair similarity was determined for monozygotic twins and siblings using Pearson pairwise correlation coefficients. Results: A leukocyte endothelial adhesion assay for lymphoblastoid cell lines was developed and optimized (CV = 8.68, Z′-factor = 0.67, SNR = 18.41). A higher adhesion correlation was found between the twins than that between the siblings. Intra-pair similarity for leukocyte endothelial adhesion in monozygotic twins was 0.60 compared to 0.25 in the siblings. The extent to which these differences are attributable to underlying genetic factors was quantified and the heritability of leukocyte endothelial adhesion was calculated to be 69.66% (p-value<0.0001). Conclusions: There is a heritable component to leukocyte endothelial adhesion. Underlying genetic predisposition plays a significant role in inter-individual variability of leukocyte endothelial adhesion. [ABSTRACT FROM AUTHOR]