No abstract

Results from the testing of 108 coded chemicals in Chinese hamster ovary (CHO) cells for the induction of chromosome aberrations and sister chromatid exchanges (SCEs) are presented. All chemicals were tested with and without exogenous metabolic activation, using protocols designed to allow testing up to toxic doses. Cell harvest times could also be extended if chemical-induced cell cycle delay was seen. Chromosome aberrations were induced by 43 of the chemicals, and 66 induced SCEs; 37 of the chemicals were positive for both endpoints.

It appears that in busy interrupt-driven clinical environments, clinicians reduce the time they spend on clinical tasks if they experience interruptions, and may delay or fail to return to a significant portion of interrupted tasks. Task shortening may occur because interrupted tasks are truncated to 'catch up' for lost time, which may have significant implications for patient safety.

The maxima of independent Weiner processes spatially normalized with time scales compressed is considered and it is shown that a weak limit process exists. This limit process is stationary, and its one-dimensional distributions are of standard extreme-value type. The method of proof involves showing convergence of related point processes to a limit Poisson point process. The method is extended to handle the maxima of independent Ornstein–Uhlenbeck processes.

Arrestins are members of a superfamily of proteins that arrest the activity of G-protein coupled receptors. Mouse cone photoreceptors express two visual arrestins, Arr1 and Arr4 (Carr). We quantified their expression levels and subcellular distributions in mouse cones: total Arr1 was estimated to be in an ~ 6:1 ratio to cone opsin, about 50-fold higher than Arr4. Recordings from single cones of Arr1−/− and Arr4−/− mice establish that both proteins are competent to arrest the activity of photoactivated S- and M- cone opsins. Recordings from Arr1−/− , Arr4−/− double-knockout mice establish a requirement for at least one of the two visual arrestins for normal cone opsin inactivation at all flash intensities. These recordings also reveal low activity photoproducts of S- and M-opsins that are absent when Grk1 and an arrestin are co-expressed, but which decay 70-fold more rapidly than the comparable photoproducts of rhodopsin in rods.

The maxima of independent Weiner processes spatially normalized with time scales compressed is considered and it is shown that a weak limit process exists. This limit process is stationary, and its one-dimensional distributions are of standard extreme-value type. The method of proof involves showing convergence of related point processes to a limit Poisson point process. The method is extended to handle the maxima of independent Ornstein–Uhlenbeck processes.

SUMMARY The spatial median, called the mediancentre in an earlier paper by J. C. Gower, is defined as the bivariate location measure to minimize the sum of absolute distances to observations. its asymptotic efficiency relative to the sample mean vector with normal data is shown to exceed the usual univariate 2/π = 0.637. its estimating equations have an angular aspect and are used to develop “angle tests”, which are analogues of sign tests in one dimension.

The shutoff mechanisms of the rod visual transduction cascade involve G-protein-coupled receptor (GPCR) kinase 1 (GRK1) phosphorylation of light-activated rhodopsin (R*) followed by rod arrestin binding. Deactivation of the cone phototransduction cascade in the mammalian retina is delineated poorly. In this study we sought to explore the potential mechanisms underlying the quenching of the phototransduction cascade in cone photoreceptors by using mouse models lacking rods and/or GRK1. Using the "pure-cone" retinas of the neural retina leucine zipper (Nrl) knock-out (KO, -/-) mice (Mears et al., 2001), we have demonstrated the light-dependent, multi-site phosphorylation of both S and M cone opsins by in situ phosphorylation and isoelectric focusing. Immunoprecipitation with affinity-purified polyclonal antibodies against either mouse cone arrestin (mCAR) or mouse S and M cone opsins revealed specific binding of mCAR to light-activated, phosphorylated cone opsins. To elucidate the potential role of GRK1 in cone opsin phosphorylation, we created Nrl and Grk1 double knock-out (Nrl-/-Grk1-/-) mice by crossing the Nrl-/- mice with Grk1-/- mice (Chen et al., 1999). We found that, in the retina of these mice, the light-activated cone opsins were neither phosphorylated nor bound with mCAR. Our results demonstrate, for the first time in a mammalian species, that cone opsins are phosphorylated and that CAR binds to phosphorylated cone opsins after light activation.