Investigation of Microstructures,Mechanical Properties of AZ91E Hybrid Composite Reinforced with Silicon Carbide and Fly Ash

Silicon - In this study, the stir casting processing technique was used to produce the AZ91E hybrid composite reinforced with Silicon Carbide (SiC) and Fly ash (FA) particles in different weight...     

Analog and RF Performance Evaluation of Junctionless Accumulation Mode (JAM) Gate Stack Gate All Around (GS-GAA) FinFET

Silicon - This work presents the analog and RF performance evaluation of Junctionless Accumulation Mode (JAM) Gate Stack Gate All Around (GS-GAA) FinFET, and the results acquired have been compared...     

Mechanical behaviour and microstructural evolution of constrained groove pressed nickel sheets

Pure nickel sheets are subjected to severe plastic deformation by constrained groove pressing technique at room temperature thereby imparting an effective plastic strain of 3.48. The evolution of mechanical behaviour with increasing number of passes revealed intensive increase in strength properties after first pass; however marginal increase is observed subsequently. Gain in ductility which is attributed to dislocation recovery is observed after third pass along with marginal drop in strength. Microstructural evolution during groove pressing of sheets is characterized by X-ray diffraction profile analysis using Williamson–Hall method. Besides the observation of strong shear texture in constrained groove pressed sheets, improvement in strain isotropy with increased straining is revealed from Williamson–Hall plots. The sub-grain/cell size estimated by analysing the diffraction profile of deformed sheets is found to be ～1390 nm after processing up to three passes. Low grain refinement efficiency observed in this process compared to other severe plastic deformation techniques at similar strain conditions is explained by the deformation characteristics and loading behaviour experienced by the sheets during constrained groove pressing.     

Microstructural evolution in liquid metal processed Al-alloy/SiCp composites

Al-Zn-Mg/SiC_P composites processed by a liquid metal processing (stir casting) technique have been microstructurally characterised in the as-cast and extruded conditions. Uniform distribution of SiC_P is observed with few defects, such as particle clusters, which are due to partial wetting and associated gas porosity. The constituent particles are associated with SiC_P although their composition remains unaffected compared with the control alloy. Hot extrusion of the composite using a shear type die showed banding of particles in the extruded direction with 9 vol. % composite. Such defects however, are not predominant in 18% SiC_P extruded composites. The presence of Mg₂Si is detected at the particle matrix interface as well as in the matrix.     

Effect of thermal oxidation on the corrosion resistance of Ti6Al4V alloy in hydrochloric and nitric acid medium

The characteristics of Ti6Al4V alloy subjected to thermal oxidation in air atmosphere at 650 °C for 48 h and its corrosion behavior in 0.1 and 4 M HCl and HNO₃ medium are addressed. When compared to the naturally formed oxide layer (～4–6 nm), a relatively thicker oxide scale (～7 µm) is formed throughout the surface of Ti6Al4V alloy after thermal oxidation. XRD pattern disclose the formation of the rutile and oxygen‐diffused titanium as the predominant phases. A significant improvement in the hardness (from 324 ± 8 to 985 ± 40 HV_0.25) is observed due to the formation of hard oxide layer on the surface followed by the presence of an oxygen diffusion zone beneath it. Electrochemical studies reveal that the thermally oxidized Ti6Al4V alloy offers a better corrosion resistance than its untreated counterpart in both HCl and HNO₃ medium. The uniform surface coverage, compactness and thickness of the oxide layer provide an effective barrier towards corrosion of the Ti6Al4V alloy. The study concludes that thermal oxidation is an effective approach to engineer the surface of Ti6Al4V alloy to increase its corrosion resistance in HCl and HNO₃ medium.     

AKT Inhibitors: The Road Ahead to Computational Modeling-Guided Discovery

AKT, is a serine/threonine protein kinase comprising three isoforms—namely: AKT1, AKT2 and AKT3, whose inhibitors have been recognized as promising therapeutic targets for various human disorders, especially cancer. In this work, we report a systematic evaluation of multi-target Quantitative Structure-Activity Relationship (mt-QSAR) models to probe AKT’ inhibitory activity, based on different feature selection algorithms and machine learning tools. The best predictive linear and non-linear mt-QSAR models were found by the genetic algorithm-based linear discriminant analysis (GA-LDA) and gradient boosting (Xgboost) techniques, respectively, using a dataset containing 5523 inhibitors of the AKT isoforms assayed under various experimental conditions. The linear model highlighted the key structural attributes responsible for higher inhibitory activity whereas the non-linear model displayed an overall accuracy higher than 90%. Both these predictive models, generated through internal and external validation methods, were then used for screening the Asinex kinase inhibitor library to identify the most potential virtual hits as pan-AKT inhibitors. The virtual hits identified were then filtered by stepwise analyses based on reverse pharmacophore-mapping based prediction. Finally, results of molecular dynamics simulations were used to estimate the theoretical binding affinity of the selected virtual hits towards the three isoforms of enzyme AKT. Our computational findings thus provide important guidelines to facilitate the discovery of novel AKT inhibitors.     

Mesenchymal Stromal Cell Therapy in Novel Porcine Model of Diffuse Liver Damage Induced by Repeated Biliary Obstruction

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p < 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-β, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine.     

Lipid Droplets and Their Autophagic Turnover via the Raft-Like Vacuolar Microdomains

Although once perceived as inert structures that merely serve for lipid storage, lipid droplets (LDs) have proven to be the dynamic organelles that hold many cellular functions. The LDs’ basic structure of a hydrophobic core consisting of neutral lipids and enclosed in a phospholipid monolayer allows for quick lipid accessibility for intracellular energy and membrane production. Whereas formed at the peripheral and perinuclear endoplasmic reticulum, LDs are degraded either in the cytosol by lipolysis or in the vacuoles/lysosomes by autophagy. Autophagy is a regulated breakdown of dysfunctional, damaged, or surplus cellular components. The selective autophagy of LDs is called lipophagy. Here, we review LDs and their degradation by lipophagy in yeast, which proceeds via the micrometer-scale raft-like lipid domains in the vacuolar membrane. These vacuolar microdomains form during nutrient deprivation and facilitate internalization of LDs via the vacuolar membrane invagination and scission. The resultant intra-vacuolar autophagic bodies with LDs inside are broken down by vacuolar lipases and proteases. This type of lipophagy is called microlipophagy as it resembles microautophagy, the type of autophagy when substrates are sequestered right at the surface of a lytic compartment. Yeast microlipophagy via the raft-like vacuolar microdomains is a great model system to study the role of lipid domains in microautophagic pathways.