BACKGROUND: Prostate-specific antigen (PSA), a widely used biomarker for prostate cancer (PCa), is encoded by a kallikrein gene (KLK3, kallikrein-related peptidase 3). Serum PSA concentrations vary in the population, with PCa patients generally showing higher PSA concentrations than control individuals, although a small proportion of individuals in the population display very low PSA concentrations. We hypothesized that very low PSA concentrations might reflect gene-inactivating mutations in KLK3 that lead to abnormally reduced gene expression.METHODS: We have sequenced all KLK3 exons and the promoter and searched for gross deletions or duplications in KLK3 in the 30 individuals with the lowest observed PSA concentrations in a sample of approximately 85 000 men from the Prostate Testing for Cancer and Treatment (ProtecT) study. The ProtecT study examines a community-based population of men from across the UK with little prior PSA testing.RESULTS: We observed no stop codons or frameshift mutations, but we did find 30 single-base genetic variants, including 3 variants not described previously. These variants included missense variants that could be functionally inactivating and splicing variants. At this stage, however, we cannot confidently conclude whether these variants markedly lower PSA concentration or activity. More importantly, we identified 3 individuals with different large heterozygous deletions that encompass all KLK3 exons. The absence of a functional copy of KLK3 in these individuals is consistent with their reduced serum PSA concentrations.CONCLUSIONS: The clinical interpretation of the PSA test for individuals with KLK3 gene inactivation could lead to false-negative PSA findings used for screening, diagnosis, or monitoring of PCa. (C) 2012 American Association for Clinical Chemistry

By modelling the axis ratio distribution of Sloan Digital Sky Survey (SDSS) Data Release 8 galaxies, we find the intrinsic 3D shapes of spirals and ellipticals. We use morphological information from the Galaxy Zoo project and assume a non-parametric distribution intrinsic of shapes, while taking into account dust extinction. We measure the dust extinction of the full sample of spiral galaxies and find a smaller value than previous estimations, with an edge-on extinction of E-0 = 0.284(-0.026)(+0.015) in the SDSS r band. We also find that the distribution of minor to major axis ratio has a mean value of 0.267 +/- 0.009, slightly larger than previous estimates mainly due to the lower extinction used; the same affects the circularity of galactic discs, which are found to be less round in shape than in previous studies, with a mean ellipticity of 0.215 +/- 0.013. For elliptical galaxies, we find that the minor to major axis ratio, with a mean value of 0.584 +/- 0.006, is larger than previous estimations due to the removal of spiral interlopers present in samples with morphological information from photometric profiles. These interlopers are removed when selecting ellipticals using Galaxy Zoo data. We find that the intrinsic shapes of galaxies and their dust extinction vary with absolute magnitude, colour and physical size. We find that bright elliptical galaxies are more spherical than faint ones, a trend that is also present with galaxy size, and that there is no dependence of elliptical galaxy shape with colour. For spiral galaxies, we find that the reddest ones have higher dust extinction as expected, due to the fact that this reddening is mainly due to dust. We also find that the thickness of discs increases with luminosity and size, and that brighter, smaller and redder galaxies have less round discs.

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Differential mobility particle sizer (DMPS) aerosol concentrations (N13-800) were collected over a one-year-period (2004) at an urban background site in Barcelona, North-Eastern Spain. Quantitative contributions to particle number concentrations of the nucleation (33-39%), Aitken (39-49%) and accumulation mode (18-22%) were estimated. We examined the source and time variability of atmospheric aerosol particles by using both K-means clustering and Positive Matrix Factorization (PMF) analysis. Performing clustering analysis on hourly size distributions, nine K-means DMPS clusters were identified and, by directional association, diurnal variation and relationship to meteorological and pollution variables, four typical aerosol size distribution scenarios were identified: traffic (69% of the time), dilution (15% of the time), summer background conditions (4% of the time) and regional pollution (12% of the time). According to the results of PMF, vehicle exhausts are estimated to contribute at least to 62-66% of the total particle number concentration, with a slightly higher proportion distributed towards the nucleation mode (34 %) relative to the Aitken mode (28-32%). Photochemically induced nucleation particles make only a small contribution to the total particle number concentration (2-3% of the total), although only particles larger than 13 nm were considered in this study. Overall the combination of the two statistical methods is successful at separating components and quantifying relative contributions to the particle number population.

This letter presents an acoustic one-channel location system that takes advantage of the multiple reflections occurring in the reverberating medium under investigation. Experimental results are obtained with guided waves propagating in a bounded aluminum plate. The plate is so designed that there is no direct propagation path between the single transducer and the region of interest in the plate. In that manner, the two-dimensional image obtained in the region of interest is only based on the reverberated acoustic field measured with the single fixed transducer. The method is based on the application of topological optimization methods to wave-based location problems and on a preliminary calibration of the whole system. This calibration mainly consists in measuring the impulse response of the transducer in the region of interest before any object or defect is present. The calibration is here performed with a Laser Doppler velocimeter. The experimental results obtained with this one-channel topological imaging method show accurate location of a single small defect and of multiple small defects, with a resolving power below the wavelength. (C) 2014 AIP Publishing LLC.

A two-step continuous-time (CT) incremental sigma-delta (ISigmaDelta) ADC, which enhances the performance of conventional CT ISigmaDelta ADCs, is proposed. By pipelining two second-order CT ISigmaDelta ADCs, the proposed two-step architecture can achieve high resolution without sacrificing the conversion rate. Compared to other alternatives, the two-step CT ISigmaDelta ADC exhibits the freedom of adjusting its accuracy and speed independently while featuring quite relaxed circuit specifications.