The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) elicits estrogenic-like microRNA responses in breast cancer cells.

The cooking of meat results in the generation of heterocyclic amines (HCA), the most abundant of which is 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Data from epidemiological, mechanistic, and animal studies indicate that PhIP could be causally linked to breast cancer incidence. Besides the established DNA damaging and mutagenic activities of PhIP, the chemical is reported to have oestrogenic activity that could contribute to its tissue specific carcinogenicity. In this study we investigated the effect of treatment with PhIP and 17-β-estradiol (E2) on global microRNA (miRNA) expression of the oestrogen responsive MCF-7 human breast adenocarcinoma cell line. PhIP and E2 caused widespread and largely over-lapping effects on miRNA expression, with many of the commonly affected miRNA reported to be regulated by oestrogen and have been implicated in the initiation and progression of breast cancer. The regulatory activity of the miRNAs we show here to be responsive to PhIP treatment, are also predicted to mediate cellular phenotypes that are associated with PhIP exposure. Consequently, this study offers further support to the ability of PhIP to induce widespread effects via activation of oestrogen receptor alpha (ERα). Moreover, this study indicates that deregulation of miRNA by PhIP could potentially be an important non-DNA-damaging carcinogenic mechanism in breast cancer. © 2014

Measuring Uncertainty in Games: Design and Preliminary Validation

Uncertainty is an important element of game play, which is widely believed to act as a precondition for player experience (PX). To investigate the concept and examine its relation to other PX concepts, we should be able to measure it. We present the design and preliminary results of the validation of the Player Uncertainty in Games (PUG) questionnaire. Based on various sources from games user research and work done with regards to searching digital archives, we designed a questionnaire that measures the experience of uncertainty in games. The scale was refined down to 66 items via interviews with players and expert reviews, which was then validated and further refined based on data gathered from gamers in an online survey. The Principal Component Analysis showed high level of internal consistency for the scale and each of its four factors: Disorientation, Exploration, Prospect, and Randomness. This work demonstrates the initial findings towards a validated tool for measuring uncertainty of players in digital games

Space storm measurements of the July 2005 solar extreme events from the low corona to the Earth

The Athens Neutron Monitor Data Processing (ANMODAP) Center recorded an unusual Forbush decrease with a sharp enhancement of cosmic ray intensity right after the main phase of the Forbush decrease on 16 July 2005, followed by a second decrease within less than 12 h. This exceptional event is neither a ground level enhancement nor a geomagnetic effect in cosmic rays. It rather appears as the effect of a special structure of interplanetary disturbances originating from a group of coronal mass ejections (CMEs) in the 13-14 July 2005 period. The initiation of the CMEs was accompanied by type IV radio bursts and intense solar flares (SFs) on the west solar limb (AR 786); this group of energetic phenomena appears under the label of Solar Extreme Events of July 2005. We study the characteristics of these events using combined data from Earth (the ARTEMIS IV radioheliograph, the Athens Neutron Monitor (ANMODAP)), space (WIND/WAVES) and data archives. We propose an interpretation of the unusual Forbush profile in terms of a magnetic structure and a succession of interplanetary shocks interacting with the magnetosphere.Comment: Advances in Space Research, Volume 43, Issue 4, p. 600-60

Emerging opportunities: the internet, marketing and museums

The tremendous impact of applying new technologies is obvious when it comes to museums. Internet forms an integral part of museums everyday life and decision making. Websites, online communities, social media, and mobile applications comprise elements of the modern museum’s digital self, which complements the real museum of permanent and temporary exhibitions, storage rooms, visitors’ facilities, laboratories and, most important, museum objects. This environment inevitably affects museum marketing strategies and creates relevant opportunities

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

The tale of the two Greeces: some management practice lessons

Based on an original double‐blind survey on randomly drawn samples of over 10,000 manufacturing firms across a range of different industries and countries, the World Management Survey is one of the first large and internationally comparable management practices data sets. In this paper, I describe and compare the performance of Greek firms to those from other countries around the world with the aim of identifying some lessons for both managers and policy makers in Greece on how to increase management quality, and hence, firms' productivity

Lost at the Edge of Uncertainty: Measuring Player Uncertainty in Digital Games

Uncertainty has previously been identified as an important ingredient of engaging games. Design in games can create different levels of uncertainty in players that they can recognize and describe as being either attributable to external forces, such as chance or hidden information, or internal to their own understanding of what to do in relation to their own goals. While it appears that uncertainty can contribute both positive and negative play experiences, there is little work in trying to operationalize and measure this concept as a component of player experience. Reported in this article is an analysis of data from over 700 players using modern bi-factor analysis techniques resulting in a five factor psychometric scale which captures the broad feelings of players about uncertainty in games. Three of these specific factors appear to point toward a single generic factor of uncertainty that is internal to the players, one captures experiences relating to external uncertainty, with the final factor relating to player’s experience of exploring the game to resolve uncertainty. In order to further validate the scale, we conducted an experiment with a commercial puzzle game manipulating the duration of play with predicted outcomes on the different specific factors of the scale. Overall the scale shows promise with good statistical reliability and construct validity of the separate factors and so will be a useful tool for further investigating player experiences in digital games

AgeDB: the first manually collected, in-the-wild age database

Over the last few years, increased interest has arisen with respect to age-related tasks in the Computer Vision community. As a result, several "in-the-wild" databases annotated with respect to the age attribute became available in the literature. Nevertheless, one major drawback of these databases is that they are semi-automatically collected and annotated and thus they contain noisy labels. Therefore, the algorithms that are evaluated in such databases are prone to noisy estimates. In order to overcome such drawbacks, we present in this paper the first, to the best of knowledge, manually collected "in-the-wild" age database, dubbed AgeDB, containing images annotated with accurate to the year, noise-free labels. As demonstrated by a series of experiments utilizing state-of-the-art algorithms, this unique property renders AgeDB suitable when performing experiments on age-invariant face verification, age estimation and face age progression "in-the-wild"

Sonic Hedgehog signalling in the regulation of barrier tissue homeostasis and inflammation

Epithelial barrier tissues such as the skin and airway form an essential interface between the mammalian host and its external environment. These physical barriers are crucial to prevent damage and disease from environmental insults and allergens. Failure to maintain barrier function against such risks can lead to severe inflammatory disorders, including atopic dermatitis and asthma. Here, we discuss the role of the morphogen Sonic Hedgehog in postnatal skin and lung and the impact of Shh signalling on repair, inflammation and atopic disease in these tissues