Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells

Sirtuin-1 (SIRT1) and SIRT6, NAD(+)-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD. Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins. Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction. Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible. Other sirtuin isoforms were not affected by miR-34a. Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases

Formality and informality in the summative assessment of motor vehicle apprentices: a case study

This article explores the interaction of formal and informal attributes of competence‐based assessment. Specifically, it presents evidence from a small qualitative case study of summative assessment practices for competence‐based qualifications within apprenticeships in the motor industry in England. The data are analysed through applying an adaptation of a framework for exploring the interplay of formality and informality in learning. This analysis reveals informal mentoring as a significant element which influences not only the process of assessment, but also its outcomes. We offer different possible interpretations of the data and their analysis, and conclude that, whichever interpretation is adopted, there appears to be a need for greater capacity‐building for assessors at a local level. This could acknowledge a more holistic role for assessors; recognise the importance of assessors’ informal practices in the formal retention and achievement of apprentices; and enhance awareness of inequalities that may be reinforced by both informal and formal attributes of assessment practices

Statistical Power, the Bispectrum and the Search for Non-Gaussianity in the CMB Anisotropy

We use simulated maps of the cosmic microwave background anisotropy to quantify the ability of different statistical tests to discriminate between Gaussian and non-Gaussian models. Despite the central limit theorem on large angular scales, both the genus and extrema correlation are able to discriminate between Gaussian models and a semi-analytic texture model selected as a physically motivated non-Gaussian model. When run on the COBE 4-year CMB maps, both tests prefer the Gaussian model. Although the bispectrum has comparable statistical power when computed on the full sky, once a Galactic cut is imposed on the data the bispectrum loses the ability to discriminate between models. Off-diagonal elements of the bispectrum are comparable to the diagonal elements for the non-Gaussian texture model and must be included to obtain maximum statistical power.Comment: Accepted for publication in ApJ; 20 pages, 6 figures, uses AASTeX v5.

Enabling the new economic actor: data protection, the digital economy, and the Databox

This paper offers a sociological perspective on data protection regulation and its relevance to design. From this perspective, proposed regulation in Europe and the USA seeks to create a new economic actor—the consumer as personal data trader—through new legal frameworks that shift the locus of agency and control in data processing towards the individual consumer or “data subject”. The sociological perspective on proposed data regulation recognises the reflexive relationship between law and the social order, and the commensurate needs to balance the demand for compliance with the design of computational tools that enable this new economic actor. We present the Databox model as a means of providing data protection and allowing the individual to exploit personal data to become an active player in the emerging data economy.The authors acknowledge the support of the EPSRC, Grants EP/M001636/1, EP/M02315X/1, EP/N028260/1, and EU FP7 Grant 611001.This is the final version of the article. It first appeared from [PUBLISHER] via http://dx.doi.org/10.1007/s00779-016-0939-

Effects of Foreground Contamination on the Cosmic Microwave Background Anisotropy Measured by MAP

We study the effects of diffuse Galactic, far-infrared extragalactic source, and radio point source emission on the cosmic microwave background (CMB) anisotropy data anticipated from the MAP experiment. We focus on the correlation function and genus statistics measured from mock MAP foreground-contaminated CMB anisotropy maps generated in a spatially-flat cosmological constant dominated cosmological model. Analyses of the simulated MAP data at 90 GHz (0.3 deg FWHM resolution smoothed) show that foreground effects on the correlation function are small compared with cosmic variance. However, the Galactic emission, even just from the region with |b| > 20 deg, significantly affects the topology of CMB anisotropy, causing a negative genus shift non-Gaussianity signal. Given the expected level of cosmic variance, this effect can be effectively reduced by subtracting existing Galactic foreground emission models from the observed data. IRAS and DIRBE far-infrared extragalactic sources have little effect on the CMB anisotropy. Radio point sources raise the amplitude of the correlation function considerably on scales below 0.5 deg. Removal of bright radio sources above a 5 \sigma detection limit effectively eliminates this effect. Radio sources also result in a positive genus curve asymmetry (significant at 2 \sigma) on 0.5 deg scales. Accurate radio point source data is essential for an unambiguous detection of CMB anisotropy non-Gaussianity on these scales. Non-Gaussianity of cosmological origin can be detected from the foreground-subtracted CMB anisotropy map at the 2 \sigma level if the measured genus shift parameter |\Delta\nu| >= 0.02 (0.04) or if the measured genus asymmetry parameter |\Delta g| >= 0.03 (0.08) on a 0.3 (1.0) deg FWHM scale.Comment: 26 pages, 7 figures, Accepted for Publication in Astrophysical Journal (Some sentences and figures modified

High-Resolution Continuum Imaging at 1.3 and 0.7 cm of the W3 IRS 5 Region

High-resolution images of the hypercompact HII regions (HCHII) in W3 IRS 5 taken with the Very Large Array (VLA) at 1.3 and 0.7 cm are presented. Four HCHII regions were detected with sufficient signal-to-noise ratios to allow the determination of relevant parameters such as source position, size and flux density. The sources are slightly extended in our ~0.2 arcsecond beams; the deconvolved radii are less than 240 AU. A comparison of our data with VLA images taken at epoch 1989.1 shows proper motions for sources IRS 5a and IRS 5f. Between 1989.1 and 2002.5, we find a proper motion of 210 mas at a position angle of 12 deg for IRS 5f and a proper motion of 190 mas at a position angle of 50 deg for IRS 5a. At the assumed distance to W3 IRS 5, 1.83 +/- 0.14 kpc, these offsets translate to proper motions of ~135 km/s and ~122 km/s$ respectively. These sources are either shock ionized gas in an outflow or ionized gas ejected from high mass stars. We find no change in the positions of IRS 5d1/d2 and IRS 5b; and we show through a comparison with archival NICMOS 2.2 micron images that these two radio sources coincide with the infrared double constituting W3 IRS 5. These sources contain B or perhaps O stars. The flux densities of the four sources have changed compared to the epoch 1989.1 results. In our epoch 2002.5 data, none of the spectral indicies obtained from flux densities at 1.3 and 0.7 cm are consistent with optically thin free-free emission; IRS 5d1/d2 shows the largest increase in flux density from 1.3 cm to 0.7 cm. This may be an indication of free-free optical depth within an ionized wind, a photoevaporating disk, or an accretion flow. It is less likely that this increase is caused by dust emission at 0.7 cm.Comment: 13 pages, 3 figures To be published in The Astrophysical Journa

Streaming Algorithm for Euler Characteristic Curves of Multidimensional Images

We present an efficient algorithm to compute Euler characteristic curves of gray scale images of arbitrary dimension. In various applications the Euler characteristic curve is used as a descriptor of an image. Our algorithm is the first streaming algorithm for Euler characteristic curves. The usage of streaming removes the necessity to store the entire image in RAM. Experiments show that our implementation handles terabyte scale images on commodity hardware. Due to lock-free parallelism, it scales well with the number of processor cores. Our software---CHUNKYEuler---is available as open source on Bitbucket. Additionally, we put the concept of the Euler characteristic curve in the wider context of computational topology. In particular, we explain the connection with persistence diagrams

Simulations from a new neutrino event generator

We construct a new Monte Carlo generator of events for neutrino interactions. The dynamical models for quasi-elastic reactions, $\Delta$ excitation and more inelastic events described by the DIS formalism with the PDFs modified according to recent JLab data are used. We describe in detail single pion production channels, which combine the $\Delta$ excitation and DIS contribution. Many comparisons of the outcome of simulations with experimental data are presented.Comment: To appear in the proceedings of 4th International Workshop on Neutrino Nucleus Interactions in the Few GeV Region (NuInt05), Okayama, Japan, 26-29 September, 200

Optical monitoring of the gravitationally lensed quasar Q2237+0305 from APO between June 1995 and January 1998

We present a data set of images of the gravitationally lensed quasar Q2237+0305, that was obtained at the Apache Point Observatory (APO) between June 1995 and January 1998. Although the images were taken under variable, often poor seeing conditions and with coarse pixel sampling, photometry is possible for the two brighter quasar images A and B with the help of exact quasar image positions from HST observations. We obtain a light curve with 73 data points for each of the images A and B. There is evidence for a long (>~ 100 day) brightness peak in image A in 1996 with an amplitude of about 0.4 to 0.5 mag (relative to 1995), which indicates that microlensing has been taking place in the lensing galaxy. Image B does not vary much over the course of the observation period. The long, smooth variation of the light curve is similar to the results from the OGLE monitoring of the system (Wozniak et al. 2000a).Comment: 8 pages, 5 figures; accepted for publication in A&