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Nowadays, mutations in the epidermal growth factor receptor (EGFR) kinase domain are studied in targeted therapy of non-small cell lung cancer (NSCLC) with EGFR tyrosine kinase inhibitors including gefitinib and erlotinib. The present study reports a rare case of a patient harboring three simultaneous EGFR mutations (L718A, Q849H, and L858R). The development of erlotinib resistance was detected in the subsequent treatment. Using a computational approach, the current study investigated the conformational changes of wild-type and mutant EGFR's kinase domains in the interaction with erlotinib. Their binding modes with erlotinib were elucidated during molecular dynamics simulation, where higher fluctuations were detected in the mutated forms of the EGFR tyrosine kinase domain. Prediction of stability and functional effect of mutations revealed that amino acidic substitutions have decreased the protein stability as well as the binding affinity to erlotinib. These results may be useful for a recommendation of EGFR mutational analysis for patients with NSCLC carcinoma.

Abstract: A technique of energy gradient carbon embedding using the filtered cathodic vacuum arc technique in the top layer of the magnetic media is evaluated for its tribological properties. Cobalt is used as the magnetic material. The embedded layer is obtained by using ion energies of 60eV and 90eV successively to embed carbon in the top layer of the magnetic media and seal the Co/C mixed layer with a few mono-layers of carbon. Auger electron spectroscopy and transmission electron microscopy are used to characterize the modified surface in terms of its thickness, structure and chemical composition. Ball-on-disk wear tests and atomic force microscopy based scratch tests are conducted on the bare cobalt and modified cobalt surfaces to characterize the wear resistance. It is observed that the wear life and scratch resistance of the cobalt surface improved considerably after the surface modification. [Copyright &y& Elsevier]