A Residual-Based HP-Mesh Optimization Technique for Petrov-Galerkin Schemes with Optimal Test Functions

In recent times, Petrov-Galerkin schemes with optimal test function framework have presented themselves as a stable and robust technique for solving partial differential equations. These schemes are also accompanied by an inbuilt error estimator, which makes them an ideal candidate for mesh adaptation. In this paper, we present a metric-based mesh adaptation strategy utilizing this inbuilt error estimator to generate optimal hp meshes

A Rare Case of Hamman Syndrome

ABSTRACT Presenting a case report of a two and half years old male baby who developed spontaneous pneumo mediastinum and subcutaneous emphysema following general anesthesia. Patient was managed with hundred percent oxygen conservatively and had a spontaneous recovery

Gajah. Securing the Future for Elephants in India.

It is estimated that six in every ten wild Asian elephants live in India. This report by the Ministry of Environment and Forests in India outlines plans to safeguard the species and associated habitats in the face of rapid economic expansion and development pressures

Covalent Cysteine Targeting of Bruton's Tyrosine Kinase (BTK) Family by Withaferin-A Reduces Survival of Glucocorticoid-Resistant Multiple Myeloma MM1 Cells

Simple Summary Glucocorticoid therapy resistance in B-cell malignancies is often associated with constitutive activation of tyrosine kinases. Novel anticancer drugs targeting hyperactivated tyrosine kinases, such as Bruton's tyrosine kinase (BTK), have, therefore, gained much interest over the past few decades and have already been approved for clinical use. In this study, we compared the therapeutic efficacy of the phytochemical kinase inhibitor withaferin A with the clinically approved BTK inhibitor ibrutinib to target hyperactivated tyrosine kinase signaling in glucocorticoid-resistant multiple myeloma cells. Our results demonstrate that withaferin A-induced cell death of glucocorticoid-resistant MM1R cells involves covalent cysteine targeting of multiple Hinge-6 domain type tyrosine kinases of the kinase cysteinome classification, including BTK. Multiple myeloma (MM) is a hematological malignancy characterized by plasma cells' uncontrolled growth. The major barrier in treating MM is the occurrence of primary and acquired therapy resistance to anticancer drugs. Often, this therapy resistance is associated with constitutive hyperactivation of tyrosine kinase signaling. Novel covalent kinase inhibitors, such as the clinically approved BTK inhibitor ibrutinib (IBR) and the preclinical phytochemical withaferin A (WA), have, therefore, gained pharmaceutical interest. Remarkably, WA is more effective than IBR in killing BTK-overexpressing glucocorticoid (GC)-resistant MM1R cells. To further characterize the kinase inhibitor profiles of WA and IBR in GC-resistant MM cells, we applied phosphopeptidome- and transcriptome-specific tyrosine kinome profiling. In contrast to IBR, WA was found to reverse BTK overexpression in GC-resistant MM1R cells. Furthermore, WA-induced cell death involves covalent cysteine targeting of Hinge-6 domain type tyrosine kinases of the kinase cysteinome classification, including inhibition of the hyperactivated BTK. Covalent interaction between WA and BTK could further be confirmed by biotin-based affinity purification and confocal microscopy. Similarly, molecular modeling suggests WA preferably targets conserved cysteines in the Hinge-6 region of the kinase cysteinome classification, favoring inhibition of multiple B-cell receptors (BCR) family kinases. Altogether, we show that WA's promiscuous inhibition of multiple BTK family tyrosine kinases represents a highly effective strategy to overcome GC-therapy resistance in MM

Synthesis and crystal growth of IR detector materials

This report pertains to the synthesis, crystal growth and characterisation of the infrared detector materials - mercury cadmium telluride (MCT) and lead tin telluride (LTD in a composition suitable for use in the 8-14 mew wavelength region. The procedures adopted for the crystal growth of MCT and LTT and the methods used for characterising the crystals for homogeneity of composition, dislocation density, energy band gap, intrinsic carrier concentration and carrier mobility are described. The results obtained from these studies are discussed. These studies indicate the suitability of these cystals for detector applications

A Hybridized Discontinuous Galerkin Solver for High-Speed Compressible Flow

We present a high-order consistent compressible flow solver, based on a hybridized discontinuous Galerkin (HDG) discretization, for applications covering subsonic to hypersonic flow. In the context of high-order discretization, this broad range of applications presents unique difficulty, especially at the high-Mach number end. For instance, if a high-order discretization is to efficiently resolve shock and shear layers, it is imperative to use adaptive methods. Furthermore, high-Enthalpy flow requires non-trivial physical modeling. The aim of the present paper is to present the key enabling technologies. We discuss efficient discretization methods, including anisotropic metric-based adaptation, as well as the implementation of flexible modeling using object-oriented programming and algorithmic differentiation. We present initial verification and validation test cases focusing on external aerodynamics