Repetitive Segmental Structure of the Transducin β Subunit: Homology with the CDC4 Gene and Identification of Related mRNAs

Retinal transducin, a guanine nucleotide regulatory protein (referred to as a G protein) that activates a cGMP phosphodiesterase in photoreceptor cells, is comprised of three subunits. We have identified and analyzed cDNA clones of the bovine transducin β subunit that may be highly conserved or identical to that in other G proteins. From the cDNA nucleotide sequence of the entire coding region, the primary structure of a 340-amino acid protein was deduced. The encoded β subunit has a Mr of 37,375 and is comprised of repetitive homologous segments arranged in tandem. Furthermore, significant homology in primary structure and segmental sequence exists between the β subunit and the yeast CDC4 gene product. The Mr 37,375 β subunit polypeptide is encoded by a 2.9-kilobase (kb) mRNA. However, there exists in retina other β-related mRNAs that are divergent from the 2.9-kb mRNA on the basis of oligonucleotide and primer-extended probe hybridizations. All mammalian tissues and clonal cell lines that have been examined contain at least two β-related mRNAs, usually 1.8 and 2.9 kb in length. These results suggest that the mRNAs are the processed products of a small number of closely related genes or of a single highly complex β gene

Regional flood estimation for ungauged basins in Sarawak, Malaysia

Abstract Design flood estimation is an important task that is required in the planning and design of many civil engineering projects. In this study, the flood records of more than 23 gauged river basins in Sarawak, Malaysia, are examined using an index-flood estimation procedure based on L-moments. Two homogeneous regions were identified and the Generalized Extreme Value and the Generalized Logistic distributions are found to describe the distribution of extreme flood events appropriately within the respective regions. A regional growth curve is subsequently developed for each of the regions. These curves can be used for the estimation of design floods in ungauged basins in Sarawak within the limitations identified for the method. The results presented herein are useful for practicing engineers in Sarawak while the general methodology may be used in any other regions, provided flood records are available

Regional flood estimation for ungauged basins in Sarawak, Malaysia

Design flood estimation is an important task that is required in the planning and design of many civil engineering projects. In this study, the flood records of more than 23 gauged river basins in Sarawak, Malaysia, are examined using an index-flood estimation procedure based on L-moments. Two homogeneous regions were identified and the Generalized Extreme Value and the Generalized Logistic distributions are found to describe the distribution of extreme flood events appropriately within the respective regions. A regional growth curve is subsequently developed for each of the regions. These curves can be used for the estimation of design floods in ungauged basins in Sarawak within the limitations identified for the method. The results presented herein are useful for practicing engineers in Sarawak while the general methodology may be used in any other regions, provided flood records are available

Service quality in the Singapore MCE industry

This paper examines the Service Quality of the Meetings, Conventions and Exhibitions industry in Singapore and recommends ways to improve this component of the industry

Acquisition of regulator on virulence plasmid of hypervirulent Klebsiella allows bacterial lifestyle switch in response to iron

MBIO14

Discovery of (2E)-3-{2-Butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile

A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC I enzyme and COLO 205 cellular IC(50)), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC(50)), and clogP, among others. These parameters were fine-tuned by carefully adjusting the substituents at positions 1 and 2 of the benzimidazole ring. After comprehensive in vitro and in vivo profiling of the selected compounds, SB939 (3) was identified as a preclinical development candidate. 3 is a potent pan-HDAC inhibitor with excellent druglike properties, is highly efficacious in in vivo tumor models (HCT-116, PC-3, A2780, MV4-11, Ramos), and has high and dos-proportional oral exposures and very good ADME, safety, and pharmaceutical properties. When orally dosed to tumor-bearing mice, 3 is enriched in tumor tissue which may contribute to its potent antitumor activity and prolonged duration of action. 3 is currently being tested in phase I and phase II clinical trials