Discovery of novel cathepsin S inhibitors by pharmacophore-based virtual high-throughput screening

The cysteine protease cathepsin S (CatS) is involved in the pathogenesis of autoimmune disorders, atherosclerosis, and obesity. Therefore, it represents a promising pharmacological target for drug development. We generated ligand-based and structure-based pharmacophore models for noncovalent and covalent CatS inhibitors to perform virtual high-throughput screening of chemical databases in order to discover novel scaffolds for CatS inhibitors. An in vitro evaluation of the resulting 15 structures revealed seven CatS inhibitors with kinetic constants in the low micromolar range. These compounds can be subjected to further chemical modifications to obtain drugs for the treatment of autoimmune disorders and atherosclerosis.

A Virtual Inspection Technique for Assessing the Dimensional Accuracy of Forged Compressor Blades Using FE Modeling and CMM Inspection

This paper presents research for developing a virtual inspection system that evaluates the dimensional tolerance of forged aerofoil blades formed using the finite element (FE) method. Conventional algorithms adopted by modern coordinate measurement processes have been incorporated with the latest free-form surface evaluation techniques to provide a robust framework for the dimensional inspection of FE aerofoil models. The accuracy of the approach had been verified with a strong correlation obtained between the virtual inspection data and coordinate measurement data from corresponding aerofoil components.