552 research outputs found

    Structure of the met protein and variation of met protein kinase activity among human tumour cell lines.

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    An in vitro autophosphorylation assay has been used to demonstrate that there is considerable variation in met associated protein kinase among human tumour cell lines. Of particular note was the very high level of autophosphorylation of the 140 kD met protein (p140met) in experiments with A431 human cervical carcinoma cells. In contrast in experiments with Daoy human medulloblastoma cells we failed to detect phosphorylation of p140met; instead a high level of phosphorylation of a 132 kD protein was observed. To help understand the basis for the variation in kinase activity and to learn more about the structure of the mature met protein we have analysed p140met in SDS-polyacrylamide gels under non-reducing conditions. Under these conditions the met protein had an apparent molecular weight of 165,000 indicating that the mature met protein may exist as an alpha beta complex in which p140met (designated the beta subunit) is joined by disulphide bonds to a smaller, 25 kD, alpha-chain. We have identified a potential proteolytic cleavage site with the sequence Lys-Arg-Lys-Lys-Arg-Ser at amino acids 303-308 in the human met protein that may account for cleavage of the met protein into alpha and beta subunits

    Convergence of forecast distributions in a 100,000-member idealised convective-scale ensemble

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    Many operational weather services use ensembles of forecasts to generate probabilistic predictions. Computational costs generally limit the size of the ensemble to fewer than 100 members, although the large number of degrees of freedom in the forecast model would suggest that a vastly larger ensemble would be required to represent the forecast probability distribution accurately. In this study, we use a computationally efficient idealised model that replicates key properties of the dynamics and statistics of cumulus convection to identify how the sampling uncertainty of statistical quantities converges with ensemble size. Convergence is quantified by computing the width of the 95% confidence interval of the sampling distribution of random variables, using bootstrapping on the ensemble distributions at individual time and grid points. Using ensemble sizes of up to 100,000 members, it was found that for all computed distribution properties, including mean, variance, skew, kurtosis, and several quantiles, the sampling uncertainty scaled as n-1/2 for sufficiently large ensemble size n. This behaviour is expected from the Central Limit Theorem, which further predicts that the magnitude of the uncertainty depends on the distribution shape, with a large uncertainty for statistics that depend on rare events. This prediction was also confirmed, with the additional observation that such statistics also required larger ensemble sizes before entering the asymptotic regime. By considering two methods for evaluating asymptotic behaviour in small ensembles, we show that the large-n theory can be applied usefully for some forecast quantities even for the ensemble sizes in operational use today

    Cortisol and testosterone increase financial risk taking and may destabilize markets

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    It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders’ financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways.This work was supported by the Economic and Social Research Council (grant ES/G005230/1). CC was supported by the Spanish Ministerio de Economía y Competitividad (ECO2012-34928). PNT was supported by the Swiss National Science Foundation (PP00P1_128574 PP00P1_150739 and CRSII3_141965). RER was supported by the UK Medical Research Council (Mr/J004685/1)

    Comparative genomics in chicken and Pekin duck using FISH mapping and microarray analysis

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    BACKGROUND: The availability of the complete chicken (Gallus gallus) genome sequence as well as a large number of chicken probes for fluorescent in-situ hybridization (FISH) and microarray resources facilitate comparative genomic studies between chicken and other bird species. In a previous study, we provided a comprehensive cytogenetic map for the turkey (Meleagris gallopavo) and the first analysis of copy number variants (CNVs) in birds. Here, we extend this approach to the Pekin duck (Anas platyrhynchos), an obvious target for comparative genomic studies due to its agricultural importance and resistance to avian flu. RESULTS: We provide a detailed molecular cytogenetic map of the duck genome through FISH assignment of 155 chicken clones. We identified one inter- and six intrachromosomal rearrangements between chicken and duck macrochromosomes and demonstrated conserved synteny among all microchromosomes analysed. Array comparative genomic hybridisation revealed 32 CNVs, of which 5 overlap previously designated "hotspot" regions between chicken and turkey. CONCLUSION: Our results suggest extensive conservation of avian genomes across 90 million years of evolution in both macro- and microchromosomes. The data on CNVs between chicken and duck extends previous analyses in chicken and turkey and supports the hypotheses that avian genomes contain fewer CNVs than mammalian genomes and that genomes of evolutionarily distant species share regions of copy number variation ("CNV hotspots"). Our results will expedite duck genomics, assist marker development and highlight areas of interest for future evolutionary and functional studies
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