Analysis of thermomechanical stresses in dual compound thick cylinders under asymmetric loads: An analytical and numerical method.

This study presents a 2D comprehensive analytical and numerical analysis of the thermomechanical stresses in an unsymmetric dual compound thick cylinder under steady-state conditions. By employing mathematical analysis, this research aims to investigate the effectiveness of a 2D compound cylinder in reducing elastic and thermoelastic stresses. The temperature and displacement fields are thought to be dependent on the radial and circumferential directions, subject to asymmetric thermal and mechanical boundary conditions on the inner and outer surfaces. In this scenario, the Poisson ratio is considered to be a constant. The techniques of variable separation and complex Fourier series are employed analytically in the solution of heat conduction and Navier equations. The results obtained from the developed analytical method are compared and validated against those obtained from a finite difference method (FDM). The findings of this study suggest that the clamping of the outer layer has a significant influence on stress distribution in the structure, and the impact of tangential stress on the behavior of a compound cylinder is highly dominant. Furthermore, changes in temperature significantly influence hoop stress compared to variations in internal pressure levels. Moreover, the influence of internal pressure is relatively attenuated when a pressure vessel is fabricated utilizing different metals. In addition, the findings indicated that the configuration of layers and the location of the highest temperature had a significant impact on the performance of the vessel. Nevertheless, the technology provided has sufficient robustness to effectively address the complexities associated with the design of multilayered graded materials (GM) in additive manufacturing applications.

Analytical and numerical (FEA) solution for steady-state heat transfer in generic FGM cylinder coated with two layers of isotropic material under convective-radiative boundary conditions.

An investigation was carried out in order to develop an accurate analytical solution and a numerical (FEA) solution for steady-state heat transfer in a circular sandwich structure incorporated with convective-radiative boundary conditions. The dimensional governing equations and boundary conditions were developed in the form of a 4th order algebraic equation, and then the solution was obtained using Ferrari's method. By solving for the roots of the quartic equation, we were able to determine the dimensionless temperature fields of the FG sandwich composite. The findings obtained utilizing the exact analytical solution for the FG sandwich composite under thermal loads were satisfactorily validated against those data obtained using the Galerkin finite element approximation. The impact of geometric and thermo-physical characteristics, such as Biot number (Bii=1,2), Inner and outer surface thickness ratio (ri=1,2Ro), ambient temperature ratio (θd), radiation-conduction parameter (Nr), and thermal conductivity ratio (λ3λ1) on the efficiency of heat transfer, has also been studied. This study reveals the distinct effect of Biot number on the inner and outer layers of the composite cylinder. It shows that Bi1 has a negligent effect on temperature distribution; on the other hand, the outer surface (Bi2≤1) minimizes temperature variation. However, for design consideration, a thicker inner face sheet is not recommended in high thermal load, as Nr>4 has an insignificant impact on inner surface thickness on top surface temperature. Moreover, the outer surface temperature appears to be more sensitive to θd than the radiation-convection side. Furthermore, the given analytical solution is adequately verified against the proposed FEA method, having an error of less than 1.5%.

Stabilizing hydroperoxyflavin intermediate formation via a peptide appendage: a neutral flavoenzyme model.

A bioinspired mimic for the stabilization of hydroperoxyflavin intermediate formation was designed and investigated for monooxygenase like catalytic properties. A suitable peptide appendage was covalently linked to the C7-position of the neutral isoalloxazine core to synthesize Fl-G, Fl-F, Fl-P, and Fl-ßA analogues. While the presence and identity of the peptide appendage were found to be crucial for catalytic efficiency, corroborative observations were made from theoretical studies as well, supporting the precise conformational and accessibility requirements for the stabilization of the key hydroperoxyflavin intermediate. A simple yet elegant flavopeptide model (Fl-G) was found to achieve almost quantitative catalytic efficiency compared to the control flavin analogue without a peptide appendage.

How the structural properties of the indole derivatives are important in kinase targeted drug design?: A case study on tyrosine kinase inhibitors.

Kinases are considered as important signalling enzymes that illustrate 20% of the druggable genome. Human kinase family comprises >500 protein kinases and about 20 lipid kinases. Protein kinases are responsible for the mechanism of protein phosphorylation. These are necessary for regulation of various cellular activities including proliferation, cell cycle, apoptosis, motility, growth, differentiation, etc. Their deregulation leads to disruption of many cellular processes leading to different diseases most importantly cancer. Thus, kinases are considered as valuable targets in different types of cancer as well as other diseases. Researchers around the world are actively engaged in developing inhibitors based on distinct chemical scaffolds. Indole represents as a versatile scaffold in the naturally occurring and bioactive molecules. It is also used as a privileged scaffold for the target-based drug design against different diseases. This present article aim to review the applications of indole scaffold in the design of inhibitors against different tyrosine kinases such as epidermal growth factor receptors (EGFRs), vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), etc. Important structure activity relationships (SARs) of indole derivatives were discussed. The present work is an attempt to summarize all the crucial structural information which is essential for the development of indole based tyrosine kinase inhibitors with improved potency.

Identification of structural fingerprints for in vivo toxicity by using Monte Carlo based QSTR modeling of nitroaromatics.

Monte Carlo based method by using either SMILES based or combination of SMILES and Graph-based descriptors is an important strategy to build the QSAR/QSTR model for prediction of different biological endpoints. In this study, Monte Carlo based QSTR approach was applied to the dataset of 90 nitroaromatic compounds related to their in vivo toxicity, represented by 50% lethal dose concentration for rats (LD50). Both classification and regression-based QSTR models were developed to get an idea about different fingerprints for promoters and hinderers of nitroaromatics toxicity. The best classification model was obtained by using SMILES and graph-based (GAO) descriptor with 1ECK connectivity (sensitivity = 0.7143, specificity = 1.0000, accuracy = 0.8889, and MCC = 0.7774). The best regression model calculated by using SMILES and hydrogen-suppressed graph descriptors with 0ECk connectivity (R2 = 0.7386, Q2 = 0.6315, S = 0.467, and MAE = 0.340). Finally, a consensus QSTR model was generated to predict efficiently the toxicity of new compounds. The study highlighted that the comparative QSTR models by using the Monte Carlo method can also be generated and will be a useful tool for structural fingerprint analysis in case of nitroaromatics for preliminary evaluation of its toxicity to mammals.