Stabilised p53 facilitates aneuploid clonal divergence in colorectal cancer

Mutations in the p53 tumour suppressor gene are amongst the most frequent genetic abnormalities acquired in tumours. Recent studies in vitro suggest that mutant p53 destabilises the genome and facilitates development of aneuploidy. Here, in a study of 83 colorectal carcinomas, we demonstrate that alterations in p53 (detected by immunocytochemical stabilisation) precede and apparently facilitate divergence of aneuploid sub-clones. Aneuploidy in these tumours (but not those with normal p53) is predominantly in the subtetraploid range, suggesting that endoreduplication is important in its origin. This association with a specific phase of carcinoma progression is not shared by other commonly acquired genetic abnormalities in these tumours. These observations highlight the critical role of p53 in the regulation of abnormal chromosome replication and afford an explanation for the association between p53 abnormalities, aneuploidy and biological aggression in cancer.     

Series analysis of valid sequences in calculation of synchronisation delay for T-codes

An analysis of the series encountered in Higgie's algorithm of computing average synchronisation delay for T-codes is presented. Convergence for the limiting case of those series is established and an analytical method is developed to verify a result previously found by simulation. These lead to significant improvement in the algorithm, facilitating the search for optimal T-codes for any information source.     

Transmission outage models for sub-transmission network reliabilityevaluation

Methods are presented for modeling the failure and repair of transmission equipment and their impact on subtransmission system reliability. The methods account for arbitrary load variation and nonexponential downtime distribution for components. The effects of single independent outages common-mode outages and independent overlapping outages are studied. The results are used to identify conditions when nonexponentially distributed downtimes can lead to significant errors if the method of analysis does not take this factor into account     

Water bamboo husk reinforced poly(lactic acid) green composites

The water bamboo husk is one of major agricultural wastes in Taiwan. In this study, the powder obtained from the water bamboo husk was added to poly(lactic acid) (PLA) to form novel reinforced biodegradable composites. Morphologies, mechanical properties, and heat resistance of these water bamboo powder reinforced composites were investigated. The results indicate that the char yields were increased as plant powder was incorporated to PLA. In addition, the mechanical properties were also enhanced due to the addition of powders. The increments of storage moduli of PLA were about 50–200%. Moreover, the increments of loss moduli of PLA were about 70–200%. On the other hand, the T_g of PLA was slightly decreased by the addition of powder, and this may improve the brittle characteristics of PLA. Furthermore, this type of reinforced PLA would be more environmental friendly than the artificial additive‐reinforced one. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers     

Design, synthesis, and characterization of a photoactivatable flavocytochrome molecular maquette

We report the construction of a synthetic flavo-heme protein that incorporates two major physiological activities of flavoproteins: light activation of flavin analogous to DNA photolyase and rapid intramolecular electron transfer between the flavin and heme cofactors as in several oxidoreductases. The functional tetra-alpha-helix protein comprises two 62-aa helix-loop-helix subunits. Each subunit contains a single cysteine to which flavin (7-acetyl-10-methylisoalloxazine) is covalently attached and two histidines appropriately positioned for bis-his coordination of heme cofactors. Both flavins and hemes are situated within the hydrophobic core of the protein. Intramolecular electron transfer from flavosemiquinone generated by photoreduction from a sacrificial electron donor in solution was examined between protoporphyrin IX and 1-methyl-2-oxomesoheme XIII. Laser pulse-activated electron transfer from flavin to meso heme occurs on a 100-ns time scale, with a favorable free energy of approximately -100 meV. Electron transfer from flavin to the lower potential protoporphyrin IX, with an unfavorable free energy, can be induced after a lag phase under continuous light illumination. Thus, the supporting peptide matrix provides an excellent framework for the positioning of closely juxtaposed redox groups capable of facilitating intramolecular electron transfer and begins to clarify in a simplified and malleable system the natural engineering of flavoproteins.     

Long-term progression in chronic manganism: ten years of follow-up

We studied the long-term clinical course of five patients with chronic manganese intoxication. The mean scores of the King's College Hospital Rating Scale for Parkinson's disease increased from 15.0 +/- 4.2 in 1987 to 28.3 +/- 6.70 in 1991 and then to 38.1 +/- 12.9 in 1995. The deterioration was most prominent in gait, rigidity, speed of foot tapping, and writing. Tissue concentrations of manganese in blood, urine, scalp hair, and pubic hair returned to normal. Follow-up MRIs did not show paramagnetic high-signal intensity on T1-weighted images. The data indicate that clinical progression in patients with manganese parkinsonism continues even 10 years after cessation of exposure.