50 research outputs found

    Interactions between dislocations and three-dimensional annealing twins in face centered cubic metals

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    Annealing twins often form in metals with a face centered cubic structure during thermal and mechanical processing. Here, we conducted molecular dynamic (MD) simulations for copper and aluminum to study the interaction processes between {1 1 1}1/2 \u3c1 1 0\u3e dislocations and a three-dimensional annealing twin. Twin boundaries are characterized with Σ3{1 1 1} coherent twin boundaries (CTBs) and Σ3{1 1 2} incoherent twin boundaries (ITBs). MD results revealed that dislocation-ITB interactions affect slip transmission for a dislocation crossing CTBs, facilitating the nucleation of Lomer dislocation

    Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice

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    Foxp3+ regulatory T cells (Tregs) play a critical role in maintaining immune self-tolerance. Reduced number and activity of Tregs are usually found in autoimmune and inflammatory diseases, and enhancing the differentiation of Tregs may be a promising therapeutic strategy. Some reports suggested an anti-inflammatory and anti-autoimmune potential for fenofibrate, a hypolipidemic drug used worldwide, whose lipid effects are mediated by the activation of peroxisome proliferator-activated receptor α (PPARα). In the present paper, we found that fenofibrate dose-dependently increased transforming growth factor-β and interleukin-2-induced Treg differentiation in vitro, by 1.96-fold from 0 to 20 μM (12.59 ± 1.34% to 24.69 ± 3.03%, P < 0.05). Other PPARα activators, WY14643 (100 μM), gemfibrozil (50 μM), and bezafibrate (30 μM), could not enhance Treg differentiation. In addition, PPARα could not upregulate the promoter activity of the Treg-specific transcription factor Foxp3. Fenofibrate might exert its function by enhancing Smad3 phosphorylation, a critical signal in Treg differentiation, via Akt suppression. Our work reveals a new PPARα independent anti-inflammatory mechanism of fenofibrate in up-regulating mouse Treg differentiation

    Fenofibrate Inhibited the Differentiation of T Helper 17 Cells In Vitro

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    Uncontrolled activity of T cells mediates autoimmune and inflammatory diseases such as multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, type 1 diabetes, and atherosclerosis. Recent findings suggest that enhanced activity of interleukin-17 (IL-17) producing T helper 17 cells (Th17 cells) plays an important role in autoimmune diseases and inflammatory diseases. Previous papers have revealed that a lipid-lowering synthetic ligand of peroxisome proliferator-activated receptor α (PPARα), fenofibrate, alleviates both atherosclerosis and a few nonlipid-associated autoimmune diseases such as autoimmune colitis and multiple sclerosis. However, the link between fenofibrate and Th17 cells is lacking. In the present study, we hypothesized that fenofibrate inhibited the differentiation of Th17 cells. Our results showed that fenofibrate inhibited transforming growth factor-β (TGF-β) and IL-6-induced differentiation of Th17 cells in vitro. However, other PPARα ligands such as WY14643, GW7647 and bezafibrate did not show any effect on Th17 differentiation, indicating that this effect of fenofibrate might be PPARα independent. Furthermore, our data showed that fenofibrate reduced IL-21 production and STAT3 activation, a critical signal in the Th17 differentiation. Thus, by ameliorating the differentiation of Th17 cells, fenofibrate might be beneficial for autoimmunity and inflammatory diseases

    Long-term functional maintenance of primary human hepatocytes in vitro

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    The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.</p

    Interactions between dislocations and three-dimensional annealing twins in face centered cubic metals

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    Annealing twins often form in metals with a face centered cubic structure during thermal and mechanical processing. Here, we conducted molecular dynamic (MD) simulations for copper and aluminum to study the interaction processes between {1 1 1}1/2 \u3c1 1 0\u3e dislocations and a three-dimensional annealing twin. Twin boundaries are characterized with Σ3{1 1 1} coherent twin boundaries (CTBs) and Σ3{1 1 2} incoherent twin boundaries (ITBs). MD results revealed that dislocation-ITB interactions affect slip transmission for a dislocation crossing CTBs, facilitating the nucleation of Lomer dislocation

    Research on the Coupled Relationship of Factors Influencing Construction Workers’ Unsafe Behaviors: A Hybrid DEMATEL-ISM-MICMAC Approach

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    The unsafe behavior of construction workers is the most direct reason of frequent construction site accidents. In order to improve the safety management of construction sites and figure out the causal relationship among the influencing factors in the field of construction workers’ unsafe behaviors, literature research, questionnaire survey, decision-making trial, and evaluation laboratory—interpretive structural modeling—crossimpact matrix multiplication applied to classification (DEMATEL-ISM-MICMAC) methods were used in combination in this thesis. The analysis of collected data was carried out in three dimensions: individual, organizational environment, and safety management. A framework about influencing factors of construction workers’ unsafe behaviors was constructed. DEMATEL-ISM was used to construct the explanatory structural model, which to analyze the influence relationships and hierarchical relationships among factors. MICMAC method was used to analyze the driving dependency. ISM model consists of six parts, the bottom of which includes three influencing factors: work environment, safety supervision, and concernment of superior. With characteristics of high drive and low dependence, the bottom layer are the root causes of construction workers’ unsafe behaviors. Work environment and concernment of superior are the core indicators of it. The intermediate layer with a low drive and low dependence covers six factors: psychological status, physical health, professional skills, organizational climate, work quota, and safety plan. It is the indirect factor to influence construction workers’ unsafe behaviors. The top layer is composed of safety awareness, safety education, and technical delivery. Safety awareness is the core of individual dimension, showing the characteristics of low drive and high dependence, is the direct factor to influence construction workers’ unsafe behaviors. Based on the DEMATEL-ISM-MICMAC method, the methodology to reduce construction workers’ unsafe behaviors was proposed

    Texture Evolution and Nanohardness in Cu-Nb Composite Wires

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    Multifilamentary microcomposite copper-niobium (Cu-Nb) wires were fabricated by a series of accumulative drawing and bonding steps (ADB). The texture of the Cu matrix in these wires was studied using electron backscattered diffraction (EBSD) and transmission electron microscopy (TEM). Dynamic recrystallization during cold drawing caused a weakening of the &lt;111&gt; texture in the micron-scale Cu matrix at high values of true strain. A sharp &lt;111&gt; texture was observed in the nano-scale Cu matrix due to the suppression of dynamic recrystallization. The grain size was reduced by the higher level of dynamic recrystallization at high strains. The relation between the nanoindentation behavior of the different Cu matrix and the grain sizes, Cu-Nb interface, and texture was established

    Pore structure of porous Mg-1Mn-xZn alloy fabricated by metal–gas eutectic unidirectional solidification

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    Lotus-type porous Mg-1 wt.% Mn-xZn (x = 0 wt.%, 1 wt.% and 2 wt.%) alloys were fabricated by metal–gas eutectic unidirectional solidification (the Gasar method). Effects of Zn addition and the fabrication process on the porosity, pore diameter and microstructure of the porous Mg alloys were investigated. Zn addition from 0 wt.% to 1 wt.% and 2 wt.% to the Mg-1 wt.% Mn alloy decreased the porosity from 41.2% to 36.9% and 35.8%, respectively, with the same preparation processing. In the lotus-type porous Mg-1 wt.%Mn-1 wt.%Zn alloy, the porosities and average pore diameters changed with hydrogen pressures from 0.1 to 0.6 MPa. Conical areas that were rich in elemental Zn existed below the directional pores, and precipitates were also found in conical areas. Homogeneous directional pores existed in the lower portion of the ingot, and coarser directional pores and finer non-directional pores formed in the upper part. A theoretical model of the change in porosity with hydrogen pressure agreed well with the calculated porosities in the steady bubble growing area. The compressive strength of Mg-1 wt.Mn-Zn alloys can be increased by around 20  MPa through rising Zinc content from 1 wt.% to 2 wt.%, which basically linearly decline with the increasing of porosity. This work provides the basis for Gasar Mg-Zn-Mn alloy synthesis in biological applications and shows that the Gasar process is a promising method to fabricate Mg-Zn-Mn alloys with directional pores and a controllable pore structure

    Function of cleavage strength for symmetrical tilt grain boundaries

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    The cleavage strength for grain boundaries (GBs) plays a crucial role in understanding the GBs' behavior and microstructure evolution during deformation. However, its universal discipline remains uncertain, and a quantitative description is currently unavailable. Here we propose the theoretical models to systematically quantify the strength of symmetrical tilt GBs in the discrete atomic perspectives. Specifically, based on the interaction of metallic atomic pairs, the interaction between the arbitrary parallel planes is expressed by considering the atomic pair distribution on both sides of the separated planes. On this basis, the function of GBs' cleavage strength is proposed by considering that the interaction at GBs is composed of the interaction of the interfaces that make up GBs and the interaction between mirror atomic pairs at both sides of the symmetry plane. Furthermore, the theoretical prediction of the critical energy release rate Gc for the sharp crack extension is proposed based on the present cleavage strength function. All the theoretical models are validated by the ab initio simulations or citations. This work quantitatively proposes the cleavage strength function of symmetrical tilt GBs, predicts the critical energy release rate for cleavage, and provides a new methodology for studying mechanical properties of materials in the discrete atomic perspectives
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