Buckling behavior of multilayer cylindrical shells composed of functionally graded nanocomposite layers under lateral pressure in thermal environments

In this study, the stability behavior of multilayer cylindrical shells made of functionally graded nanocomposite layers (FG-NCLs) subjected to the lateral pressure in thermal environments is investigated. It is postulated that nanocomposite layers forming layered cylindrical shells are made of single-walled carbon nanotube (SWCNT)-reinforced polymers that have four types of profiles based on the uniform and linear distributions of mechanical properties. The material properties of SWCNTs are assumed to be dependent on location as well as temperature and are obtained from molecular dynamics simulations. The governing equations are derived as partial differential equations within shear deformation theory (SDT) and solved in a closed form, using the Galerkin procedure, to determine the lateral critical pressure (LCP) in thermal environments. The numerical representations relate to the buckling behavior of multilayer cylindrical shells made of functionally graded nanocomposite layers under the uniform lateral pressure for different CNT patterns and temperatures within SDT and Kirchhoff-Love theory (KLT)

Enhanced Potency of Bivalent Small Molecule gp41 Inhibitors

Low molecular weight peptidomimetic inhibitors with hydrophobic pocket binding properties and moderate fusion inhibitory activity against HIV-1 gp41-mediated cell fusion were elaborated by increasing the available surface area for interacting with the heptad repeat-1 (HR1) coiled coil on gp41. Two types of modifications were tested: 1) increasing the overall hydrophobicity of the molecules with an extension that could interact in the HR1 groove, and 2) forming symmetrical dimers with two peptidomimetic motifs that could potentially interact simultaneously in two hydrophobic pockets on the HR1 trimer. The latter approach was more successful, yielding 40–60 times improved potency against HIV fusion over the monomers. Biophysical characterization, including equilibrium binding studies by fluorescence and kinetic analysis by Surface Plasmon Resonance, revealed that inhibitor potency was better correlated to off-rates than to binding affinity. Binding and kinetic data could be fit to a model of bidentate interaction of dimers with the HR1 trimer as an explanation for the slow off-rate, albeit with minimal cooperativity due to the highly flexible ligand structures. The strong cooperativity observed in fusion inhibitory activity of the dimers implied accentuated potency due to the transient nature of the targeted intermediate. Optimization of monomer, dimer or higher order structures has the potential to lead to highly potent non-peptide fusion inhibitors by targeting multiple hydrophobic pockets

The Importance of Analytical Chemistry in Therapeutic Drug Monitoring for Personalized Medicine

Personalized therapy (PM) has the potential to adapt treatment with the best response and highest safety to provide better patient care. Key data is drug concentration of biological materials such as plasma and serum.Individual drug therapy means, choice of a drug and its dose regime should fit every individual specifically. Thus efficacy of a drug treatment would improve significantly. When developing an analytical method for (Therapeutic drug monitoring) TDM, it is important to choose a clinically relevant calibration range. This quantitation range should be built around the proposed target concentration, covering majority of samples as seen in the clinic (Ciocan-Cartita et al. 2019).Inter-individual variability in Pharmacokinetic variables may affect the blood concentration of drug so TDM approaches could solve the dosing problem.To achieve individual drug therapy with a reasonably predictive outcome, one must further account for different patterns of drug response among geographically and ethnically distinct populations. Keywords: LC-MS/MS, Therapeutic Drug Monitoring, Lenalidomide, Anastrozole DOI: 10.7176/CMR/12-7-05 Publication date:September 30th 202

Temperature-dependent nonlinear analysis of shallow shells: A theoretical approach

The paper presents a theoretical formulation for the computation of temperature-dependent nonlinear response of shallow shells with single and double curvatures subjected to transverse mechanical loads while being exposed to through-depth non-uniform heating regimes such as those resulting from a fire. The material nonlinearity arises from taking into consideration the degradation of the material elastic behaviour at elevated temperatures under quasi-static conditions. Two types of boundary conditions are considered, both of which constrain the transverse deflections and allow the rotations about the edge axis to be free. One of the boundary conditions permits lateral translation (laterally unrestrained) and the other one does not (laterally restrained). A number of examples are solved for shallow shells under different types of loading conditions including: an exponential "short hot" fire leading to a high temperature over a relatively short duration; and an exponential "long cool" fire of lower temperature over a longer duration. The limits of the shallow shell equations are investigated through comparison studies. Results show that while current numerical approaches for analysis of laterally restrained shallow shells are often computationally intensive, the proposed approach offers an adequate level of accuracy with a rapid convergence rate for such structures.The Edinburgh Research Partnership in Engineering (ERPE)

Total Synthesis of a Dimeric Thymol Derivative Isolated from Arnica sachalinensis

The total synthesis of a dimeric thymol derivative (thymarnicol) isolated from Arnica sachalinensis was accomplished in 6 steps. A key biomimetic Diels–Alder dimerization was found to occur at ambient temperature and the final oxidative cyclization occurs when the substrate is exposed to air and visible light. These results indicate that this natural product is likely the result of spontaneous (non‐enzyme‐mediated) reactivity

On thermo-mechanical nonlinear behaviour of shallow shells

The structural performance of thin shells is largely dictated by their curvature and the degree of lateral restraint at the shell edges. The present study is an attempt to theoretically investigate the influence of such factors on nonlinear thermo-mechanical response of shallow shells with single and double curvatures. For the mechanical loading, a transverse load is assumed and for the thermal loading, a through-depth thermal gradient is applied on the shallow shell. Two types of boundary conditions are considered for the shallow shell, both of which constrain transverse deflections of the shell but allow rotations parallel to the shell boundaries to be free. One of the boundary conditions permits lateral translation (laterally unrestrained) and the other one does not (laterally restrained). The fundamental nonlinear equations of shallow shells are derived based on the quasi-static conditions. The validity and reliability of the proposed approach is assessed by calculating several numerical examples for shallow shells under various mechanical and thermal loads. It is found that the proposed formulation, in particular, can adequately capture the nonlinear behaviour of laterally restrained shallow shells