Boceprevir is a hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease inhibitor that is currently being evaluated in combination with peginterferon alfa-2b and ribavirin in phase 3 studies. The clinical resistance profile of boceprevir is not characterized in detail so far. The NS3 protease domain of viral RNA was cloned from HCV genotype 1-infected patients (n ‫؍‬ 22). A mean number of 47 clones were sequenced before, at the end, and after treatment with 400 mg boceprevir twice or three times daily for 14 days for genotypic, phenotypic, and viral fitness analysis. At the end of treatment, a wild-type NS3 protease sequence was observed with a mean frequency of 85.9%. In the remaining isolates, five previously observed resistance mutations (V36M/A, T54A/S, R155K/T, A156S, V170A) and one mutation (V55A) with unknown resistance to boceprevir were detected either alone or in combination. Phenotypic analysis in the HCV replicon assay showed low (V36G, T54S, R155L; 3.8-to 5.5-fold 50% inhibitory concentration [IC 50 ]), medium (V55A, R155K, V170A, T54A, A156S; 6.8-to 17.7-fold IC 50 ) and high level (A156T; >120-fold IC 50 ) resistance to boceprevir. The overall frequency of resistant mutations and the level of resistance increased with greater declines in mean maximum HCV RNA levels. Two weeks after the end of treatment, the frequency of resistant variants declined and the number of wild-type isolates increased to 95.5%. With the exception of V36 and V170 variants all resistant mutations declined by more than 50%. Mathematical modeling revealed impaired replicative fitness for all single mutations, whereas for combined mutations a relative increase of replication efficiency was suggested. Conclusion: During boceprevir monotherapy, resistance mutations at six positions within the NS3 protease were detected by way of clonal sequence analysis. All mutations are associated with reduced replicative fitness estimated by mathematical modeling and show cross-resistance to telaprevir.

The synthesis of large lattice mismatch metal-semiconductor core-shell hetero-nanostructures remains challenging, and thus the corresponding optical properties are seldom discussed. Here, we report the gold-nanorodseeded growth of Au-CdS core-shell hetero-nanorods by employing Ag 2 S as an interim layer that favors CdS shell formation through a cation-exchange process, and the subsequent CdS growth, which can form complete coreshell structures with controllable shell thickness. Exciton-plasmon interactions observed in the Au-CdS nanorods induce shell thickness-tailored and red-shifted longitudinal surface plasmon resonance and quenched CdS luminescence under ultraviolet light excitation. Furthermore, the Au-CdS nanorods demonstrate an enhanced and plasmon-governed two-photon luminescence under near-infrared pulsed laser excitation. The approach has potential for the preparation of other metal-semiconductor hetero-nanomaterials with complete core-shell structures, and these Au-CdS nanorods may open up intriguing new possibilities at the interface of optics and electronics.

This review describes the recent progress in computational catalysis that has addressed the C–H bond activation of light alkanes.

We report a remarkable transformation of multiwalled carbon nanotubes (MWCNTs) to curved graphene nanosheets (CGN) by the Hummers method. Through this simple process, MWCNTs can be cut and unzipped in the transverse and longitudinal directions, respectively. The as-obtained CGN possess the unique hybrid structure of 1D nanotube and 2D graphene. Such a particular structure together with the improved effective surface area affords high specific capacitance and good cycling stability during the charge-discharge process when used as supercapacitor electrodes. The electrochemical measurements show that CGN exhibit higher capacitive properties than pristine MWCNTs in three different types of aqueous electrolytes, 1 M KOH, 1 M H(2)SO(4), and 1 M Na(2)SO(4). A specific capacitance of as high as 256 F g(-1) at a current density of 0.3 A g(-1) is achieved over the CGN material. The improved capacitance may be attributed to high accessibility to electrolyte ions, extended defect density, and increased effective surface area. Meanwhile, this high-yield production of graphene from low cost MWCNTs is important for the scalable synthesis and industrial application of graphene. Furthermore, this novel CGN nanostructure could also be promisingly applied in many fields such as nanoelectronics, sensors, nanocomposites, batteries, and gas storage.