Identification of GSK625433: A novel clinical candidate for the treatment of hepatitis C.

Hepatitis C is an infection of the liver caused by a pos. single-stranded RNA virus (HCV) which affects 170 million people worldwide. It is responsible for 40-60% of all liver disease and is the major cause of liver transplants in the United States. The HCV NS5B gene encodes the viral RNA-dependent RNA polymerase which is essential for HCV replication. We have previously reported the identification of acylpyrrolidines as potent inhibitors of NS5B; however their activity is attenuated against genotype 1a. The design of improved broader-spectrum compds., capable of effective inhibition of both genotypes 1b and 1a is desirable. An understanding of the binding site and genotype sequence differences was utilized to design compds. with greatly enhanced genotype 1a and 1b potency. Our studies led to the identification of GSK625433, a potent, homochiral inhibitor of these HCV genotypes in both enzyme and sub-genomic replicon cell-based assays. GSK625433 has a good pharmacokinetic profile in pre-clin. animal species, enabling progression to clin. evaluation.

Listening – the Cinderella profile component of English

This article investigates the role of listening in English. The importance of ‘reading with the ear’ is discussed, as is research into the views of teachers and pupils on this topic. Practical suggestions are made for according to listening a more meaningful place in English. Originally English was conceived as listening and reading, talking and writing. It would enrich the conception of English as a subject to uncouple listening from talking and instead give it its place as a profile component in its own right.

Power Efficient Dynamic-Range Utilisation for DSP On FPGA

A power and resource efficient ‘dynamic-range utilisation’ technique to increase operational capacity of DSP IP cores by exploiting redundancy in the data epresentation of sampled analogue input data, is presented. By cleverly partitioning dynamic-range into separable processing threads, several data streams are computed concurrently on the same hardware. Unlike existing techniques which act solely to reduce power consumption due to sign extension, here the dynamic range is exploited to increase operational capacity while still achieving reduced power consumption. This extends an existing system-level, power efficient framework for the design of low power DSP IP cores, which when applied to the design of an FFT IP core in a digital receiver system gives an architecture requiring 50% fewer multipliers, 12% fewer slices and 51%-56% less power.