This study was carried out to determine whether polymorphisms of organic anion-transporting polypeptide 1B1 (OATP1B1) have an effect on rosuvastatin pharmacokinetics in Koreans. Among 200 subjects genotyped for OATP1B1 c.388A>G, and c.521T>C, 30 subjects were selected for the rosuvastatin pharmacokinetic study. The area under the concentration-time curve for 0 to infinity (AUC(0-infinity)) of rosuvastatin for group 1 (*1a/*1a, *1a/*1b, *1b/*1b), group 2 (*1a/*15, *1b/*15), and group 3 (*15/*15) were 111+/-49.3, 126+/-45.2, and 191+/-31.0 ng h/ml, respectively, with significant differences among the three groups (P=0.0429) and between *15/*15 and the other groups (P=0.0181). The maximum plasma concentration (Cmax) also showed a significant difference between *15/*15 and the other groups (P=0.0181). There were no significant differences in rosuvastatin-lactone pharmacokinetics among the three groups. The pharmacokinetic exposure of rosuvastatin was higher in the OATP1B1*15/*15 subjects than the others, suggesting a potential association between the OATP1B1 genetic polymorphisms and altered rosuvastatin pharmacokinetics in Korean populations.

Background: Acquired resistance to third-generation epidermal growth factor receptor (EGFR) inhibitors (eg, osimertinib) may result in MET gene amplification and/or c-MET protein overexpression. Telisotuzumab vedotin (ABBV-399; teliso-v), an antiec-MET antibody-drug conjugate that can both disrupt c-MET signaling and deliver a cytotoxic payload into tumor cells, has shown antitumor activity in a phase 1/1b trial (NCT02099058) in patients (pts) with non-small cell lung cancer (NSCLC) with c-MET overexpression. Here we describe the teliso-v plus osimertinib cohort (arm E) of this trial.Trial design: Arm E of this phase 1/1b open-label study evaluates safety, pharmacokinetics, and preliminary efficacy of teliso-v, administered intravenously once every 2 weeks, in combination with oral osimertinib (80 mg once a day) in pts with metastatic NSCLC whose disease progressed on osimertinib. Pts must have documented osimertinib-sensitive EGFR mutations, and c-MET overexpression (defined by central immunohistochemistry test) in tumor tissue obtained post-osimertinib progression. Arm E consists of safety lead-in (SLP; n¼3e6), safety evaluation (SEP; n¼3e12), and expansion (n¼3e12) phases. Teliso-v will first be evaluated at 1.6 mg/kg and escalated to 1.9 mg/kg on the basis of safety signals in SLP and SEP phases. Radiographic tumor assessments will continue until disease progression, start of a new anticancer therapy, death, or consent withdrawal. Response evaluation will be based on Response Evaluation Criteria in Solid Tumors version 1.1. Planned enrollment is 3e24 pts; to date, 3 pts are enrolled.Clinical trial identification: NCT02099058.

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Experimental studies on the aerodynamic coupling effect on natural frequencies and flutter instability of rotating disks are investigated in this paper. The experiments performed using a vacuum chamber and optical disks give two main results. One is that the aerodynamic effect by surrounding air reduces the natural frequencies and critical speeds of the vibration modes in pre-flutter regions. The other is that the natural frequency of the disk rotating at ambient atmospheric pressure is equal to that in vacuum at the flutter onset speed where the disk experiences aero-induced flutter. In post-flutter regions, the aerodynamic coupling between the disk and surrounding air increases the natural frequencies of the disk. IntroductionDuring the past few years, optical data recording, together with magnetic data recording, has made a significant contribution to the development of information storage devices. Recent trends in optical disk drives are the transition from CD drives to high-density DVD drives, the spread of several rewritable disk drives and the development of new types of information storage devices (Lee and Kim, 1998). The demand for higher data transfer rate causes a dramatic increase of rotational speeds in CD-ROM drives. During the last three years the transfer rate of the CD-ROM drive was increased from 8 · (8 times the transfer rate of the original CD-ROM) to 52X drives. DVD-ROM drives recently repeat the same step of the speed increase.As the rotational speed increases, the backward natural frequency of a rotating disk decreases and vanishes at critical speed. At the critical speed, a stationary transverse force excites resonance and causes buckling instability in the rotating disk. A single backward traveling wave is excited at a certain speed above the critical speed. However, one of important issues to be considered for higher rotational speeds is aerodynamic flutter. The self-excited vibration can be induced by the aerodynamic effect around the rotating disk. Since Lennemann (1974) studied aerodynamic effect on rotating disk files, some researchers have studied the aerodynamically induced disk vibrations. Hosaka and Crandall (1992) and Huang and Mote (1995) have investigated the vibration stability of a flexible disk spinning very close to a rigid wall. In those papers, the classical hydrodynamic lubrication theory is applied by assuming that the Reynold's number of the fluid in the gap is very small. Recently, Kim et al. (2000) has predicted that the flutter speed of a hard disk drive can be about 35,000 rpm. Lee and Kim (2002) also observed the aero-induced flutter in optical disks. A modal extraction method to predict flutter of rotating disks was studied by the estimation of nonconservative aerodynamic pressures (Hansen et al., 2001).When a disk spins in open air without an enclosure, aerodynamic flutter occurs at lower speeds than the flutter speed for the disk spinning close to a rigid wall. It is because the nonsymmetric stiffness, generated by the radial component of airflow in the l...