Evaluation of Creep and Cyclic Properties of Metals and Polyimide Composites at High Temperature

In this study, creep response of metals and polyimide composites at elevated temperatures are analyzed by using empirical models. Empirical models are typically constructed based on experimental observations and their material parameters are calibrated by fitting experimental data. Although empirical models do not provide physical insight into the creep responses of materials, they are practical in structural design applications since they are expressed in simple mathematical functions. Creep responses of Copper alloy NARloy-Z and Titanium alloy Ti-6Al-4V are analyzed in this study by using empirical approach. Deformation-mechanism maps are used to predict their creep behaviors at various stresses and temperatures, and determine the design stresses based on their creep responses. Parametric studies are also conducted to provide the basis for the parameter fitting process. Furthermore, the effect of energy dissipation is incorporated into a phenomenological viscoplastic model to further understand the creep and cyclic responses of NARloy-Z. It is noted that the phenomenological model allows for rigorously incorporating the energy dissipation effect, which is one of the prominent characteristics of time-dependent materials, while the empirical model is limited. From the analyses, it is concluded that the amount of energy dissipation is much more pronounced under cyclic loading, while it is negligible under creep loading. Higher amount of energy dissipation leads to a more pronounced stress softening behavior, which is one of the sources for material failures. The empirical model and deformation maps are extended to understand creep responses of polyimides and carbon/polyimide fiber composites at elevated temperatures. PMR-15 polyimide is used as an example to illustrate how empirical model is used to predict the creep response. Rule of mixtures is considered to capture the creep response of carbon/polyimide composite. Results showed that empirical models can give reasonable predictions of creep behaviors for alloys, polyimides, and polyimide composites along axial fiber direction. Thus, the model can be used to construct deformation maps and determine design (allowable) stresses for structural design purposes

Modeling polarization switching response of ferroelectric ceramics based on multiple natural configuration theory

Ferroelectric ceramics experience polarization switching, which is macroscopically shown by nonlinear hysteretic responses when subjected to high compressive stresses and/or high amplitude of the electric field. We model the nonlinear hysteretic response of ferroelectric ceramics by considering evolutions of microstructural changes associated with changes in the dipole orientations due to both electrical and mechanical stimuli. We adopt the theory of multiple natural configurations, associated with multiple stress-free and electric-field-free states, in incorporating the effect of microstructural changes on describing the nonlinear electro-mechanical hysteretic response of ferroelectric ceramics. The first stress-free and electric-field-free states are associated with the original microstructure of the materials, in which the dipoles in the ferroelectric ceramics are randomly oriented. The new configurations are formed when the ferroelectric ceramics are subjected to relatively large stimuli, which align the dipole orientations. As each configuration is associated with a specific microstructure (a state of dipole orientations), mechanical and electrical properties characterized at different configurations will be different. To examine the model, experimental data on PZT (lead zirconate titanate) ceramics under electric and stress fields, available in the literature, are used. The model is capable of describing the hysteretic response in PZT under electro-mechanical stimuli

Vortex Evolution Behavior in Self-Assembly of Flow Units in Metallic Glasses

Shear banding in amorphous metals originates from the activation and percolation of flow units. To uncover the self-assembly dynamics of flow units in metallic glasses, a rectangular sample with two flow units embedded in the matrix undergoing simple shearing was analyzed using finite element simulations. The vortex evolution behavior, including activation, growth, and collapse during the self-assembly of flow units, was revealed. It was found that the formation of a mature vortex indicates the onset of yielding, and the collapse of the vortex represents the percolation of flow units or shear localization. The effects of initial free volume distribution and the distance between flow units on vortex behavior were also studied. Increasing the initial free volume concentration within flow units or the matrix leads to a gentler vortex evolution process and better homogeneous plasticity. The shape of vortex tends to be "flatter" with the increase in flow units' spacing, and the optimal spacing was found to maximize the strength of the material

A Hybridization Grey Wolf Optimizer to Identify Parameters of Helical Hydraulic Rotary Actuator

Based on the grey wolf optimizer (GWO) and differential evolution (DE), a hybridization algorithm (H-GWO) is proposed to avoid the local optimum, improve the diversity of the population, and compromise the exploration and exploitation appropriately. The mutation and crossover principles of the DE algorithm are introduced into the GWO algorithm, and the opposition-based optimization learning technology is combined to update the GWO population to increase the population diversity. The algorithm is then benchmarked against nine typical test functions and compared with other state-of-the-art meta-heuristic algorithms such as particle swarm optimization (PSO), GWO, and DE. The results show that the proposed H-GWO algorithm can provide very competitive results. On this basis, the forgetting factor recursive least squares (FFRLS) method and the proposed H-GWO algorithm are combined to establish a parameter identification algorithm to identify parameters of the helical hydraulic rotary actuator (HHRA) with nonlinearity and uncertainty questions. In addition, the proposed method is verified by practical identification experiments. After comparison with the least squares (LS), recursive least squares (RLS), FFRLS, PSO, and GWO results, it can be concluded that the proposed method (H-GWO) has higher identification accuracy

Fracture Propagation Modes of Lower Cambrian Shale Filled with Different Quartz Contents under Seepage-Stress Coupling

The content and spatial distribution of brittle minerals, such as quartz, are important factors in determining the fracture initiation mechanism induced by hydraulic fracturing in shale reservoirs. To further research the impact of quartz content in shales of the Lower Cambrian Niutitang Formation in northern Guizhou on the fracture expansion of its reservoir, 7 groups of randomly filling shale models with different quartz contents were established using rock failure process analysis (RFPA2D-flow) code for numerical test studies under seepage-stress coupling, and 5 samples were also subjected to uniaxial compression tests using the INSTRON 1346 electrohydraulic servo-controlled material testing machine (200T). The results show that the average growth rate of the compressive strength and the fracture proportion for a quartz content of 50% to 65% are 4.22 and 1.15 times higher than those for 35% to 50%, respectively. Fractures sprout, expand, and breakdown in the shale matrix or at the junctions of the shale matrix and quartz grains. The mechanical properties and pattern of the fracture extension of the shale in the physical tests are similar to those in the numerical tests, indicating the reliability of the numerical simulations. The fractal dimension curves at different stress levels are divided into three stages: flattening, increasing, and surging, and the fractal dimension value for a quartz content of 50%~65% at a 100% stress level is 1.02 times higher than that for 35%~50%. The high degree of natural fracture development in high quartz content formations in shale gas reservoirs is of some reference value for logging data. The research results provide a reference value for the content and spatial distribution of brittle minerals for the initiation mechanism and fracture propagation of hydraulic fracturing in shale reservoirs

BEZ235 Increases the Sensitivity of Hepatocellular Carcinoma to Sorafenib by Inhibiting PI3K/AKT/mTOR and Inducing Autophagy

Acquired resistance of hepatocellular carcinoma (HCC) to sorafenib (SFB) is the main reason for the failure of SFB treatment of the cancer. Abnormal activation of the PI3K/AKT/mTOR pathway is important in the acquired resistance of SFB. Therefore, we investigated whether BEZ235 (BEZ) could reverse acquired sorafenib resistance by targeting the PI3K/mTOR pathway. A sorafenib-resistant HCC cell line Huh7R was established. MTT assay, clone formation assay, flow cytometry, and immunofluorescence were used to analyze the effects of BEZ235 alone or combined with sorafenib on cell proliferation, cell cycle, apoptosis, and autophagy of Huh7 and Huh7R cells. The antitumor effect was evaluated in animal models of Huh7R xenografts in vivo. Western blot was used to detect protein levels of the PI3K/AKT/mTOR pathway and related effector molecules. In vitro results showed that the Huh7R had a stronger proliferation ability and antiapoptosis effect than did Huh7, and sorafenib had no inhibitory effect on Huh7R. SFB + BEZ inhibited the activation of the PI3K/AKT/mTOR pathway caused by sorafenib. Moreover, SFB + BEZ inhibited the proliferation and cloning ability, blocked the cell cycle in the G0/G1 phase, and promoted apoptosis in the two cell lines. The autophagy level in Huh7R cells was higher than in Huh7 cells, and BEZ or SFB + BEZ further promoted autophagy in the two cell lines. In vivo, SFB + BEZ inhibited tumor growth by inducing apoptosis and autophagy. We concluded that BEZ235 enhanced the sensitivity of sorafenib through suppressing the PI3K/AKT/mTOR pathway and inducing autophagy. These observations may provide the experimental basis for sorafenib combined with BEZ235 in trial treatment of HCC

Identification and characterization of an unexpected isomerization motif in CDRH2 that affects antibody activity

ABSTRACTAspartic acid (Asp) isomerization is a spontaneous non-enzymatic post-translation modification causing a change in the structure of the protein backbone, which is commonly observed in therapeutic antibodies during manufacturing and storage. The Asps in Asp–Gly (DG), Asp–Ser (DS), and Asp–Thr (DT) motifs in the structurally flexible regions, such as complementarity-determining regions (CDRs) in antibodies, are often found to have high rate of isomerization, and they are considered “hot spots” in antibodies. In contrast, the Asp-His (DH) motif is usually considered a silent spot with low isomerization propensity. However, in monoclonal antibody mAb-a, the isomerization rate of an Asp residue, Asp55, in the aspartic acid-histidine-lysine (DHK) motif present in CDRH2 was found to be unexpectedly high. By determining the conformation of DHK motif in the crystal structure of mAb-a, we found that the Cgamma of the Asp side chain carbonyl group and the back bone amide nitrogen of successor His were in proximal contact, which facilitates the formation of succinimide intermediate, and the +2 Lys played an important role in stabilizing such conformation. The contributing roles of the His and Lys residues in DHK motif were also verified using a series of synthetic peptides. This study identified a novel Asp isomerization hot spot, DHK, and the structural-based molecular mechanism was revealed. When 20% Asp55 isomerization in this DHK motif occurred in mAb-a, antigen binding activity reduced to 54%, but the pharmacokinetics in rat was not affected significantly. Although Asp isomerization of DHK motif in CDR does not appear to have a negative impact on PK, DHK motifs in the CDRs of antibody therapeutics should be removed, considering the high propensity of isomerization and impact on antibody activity and stability

Identification and characterization of two linear epitope motifs in hepatitis E virus ORF2 protein

<div><p>Hepatitis E virus (HEV) is responsible for hepatitis E, which represents a global public health problem. HEV genotypes 3 and 4 are reported to be zoonotic, and animals are monitored for HEV infection in the interests of public hygiene and food safety. The development of novel diagnostic methods and vaccines for HEV in humans is thus important topics of research. Opening reading frame (ORF) 2 of HEV includes both linear and conformational epitopes and is regarded as the primary candidate for vaccines and diagnostic tests. We investigated the precise location of the HEV epitopes in the ORF2 protein. We prepared four monoclonal antibodies (mAbs) against genotype 4 ORF2 protein and identified two linear epitopes, G438IVIPHD444 and Y457DNQH461, corresponding to two of these mAbs using phage display biopanning technology. Both these epitopes were speculated to be universal to genotypes 1, 2, 3, 4, and avian HEVs. We also used two 12-mer fragments of ORF2 protein including these two epitopes to develop a peptide-based enzyme-linked immunosorbent assay (ELISA) to detect HEV in serum. This assay demonstrated good specificity but low sensitivity compared with the commercial method, indicating that these two epitopes could serve as potential candidate targets for diagnosis. Overall, these results further our understanding of the epitope distribution of HEV ORF2, and provide important information for the development of peptide-based immunodiagnostic tests to detect HEV in serum.</p></div