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We propose a rectifier of elastic waves in a thin plate, which is made of an elastically isotropic material containing a periodic array of triangular holes as scatterers, and demonstrate numerically that it works both for the symmetric and anti-symmetric Lamb waves as well as shear horizontal waves. The rectification is caused by the geometric effects on wave scattering due to the asymmetric scatterers, while the interplay between the mode conversion and interference effects among the scattered waves owing to the periodic arrangement of scatterers complicates it. The mechanism makes it possible to rectify the typical elastic waves in the system above the threshold frequency corresponding to the wavelength equivalent to the periodicity of scatterers. [ABSTRACT FROM AUTHOR]

Background: Thalidomide and its analogs, lenalidomide and pomalidomide (referred to as immunomodulatory imide drugs or IMiDs) have been known to treat multiple myeloma and other hematologic malignancies as well as to cause teratogenicity. Recently the protein cereblon was identified as the primary target of IMiDs, and crystallographic studies of the cereblon-IMiDs complex showed strong enantioselective binding for the ( S)-enantiomer of IMiDs. Results: Using the structures of cereblon and IMiDs [both ( S)-enantiomers and ( R)-enantiomers] we performed docking simulations in order to replicate this enantiomeric selectivity and to identify the region(s) contributing to this selectivity. We confirmed the enantioselective binding of IMiDs to cereblon with high accuracy, and propose that the hairpin connecting the β10-β11 region of cereblon (residues 351-355) contributes to this selectivity and to the increased affinity with IMiDs. Conclusions: Our docking results provide novel insights into the binding mode of IMiD-like molecules and contribute to a deeper understanding of cereblon-related biology. [ABSTRACT FROM AUTHOR]

1. The biotransformation and disposition of tivantinib in humans, dogs and rats was examined after a single oral administration of [14C]tivantinib. Tivantinib constituted no more than one-third of the plasma radioactivity in all species, demonstrating significant contribution of the metabolites to plasma radioactivity. The major circulating metabolites in all species were M4 and M5, hydroxylated metabolites at the benzyl position of the tricyclic ring, accounting for 19.3 and 12.2% of the AUC of the total radioactivity, respectively, in humans. 2. The majority of radioactivity was excreted to the feces via bile. Tivantinib was detected at trace levels in urine, feces and bile, demonstrating extensive metabolism prior to biliary excretion and nearly complete tivantinib absorption under fed conditions. 3. Seven metabolic pathways were identified for tivantinib and included six oxidations (M4, M5, M7, M8, M9 and M11) and one glucuronidation (M23). The major metabolic and excretory pathways were found to be common among all species. Species differences in the metabolic pathways included lactam metabolite (M8) formation in humans and dehydrogenated metabolite (M11) formation in animals. 4. None of the metabolites identified in this work are believed to significantly impact the efficacy or toxicity of tivantinib in humans. [ABSTRACT FROM AUTHOR]