Regulating STING in health and disease.

The presence of cytosolic double-stranded DNA molecules can trigger multiple innate immune signalling pathways which converge on the activation of an ER-resident innate immune adaptor named "STimulator of INterferon Genes (STING)". STING has been found to mediate type I interferon response downstream of cyclic dinucleotides and a number of DNA and RNA inducing signalling pathway. In addition to its physiological function, a rapidly increasing body of literature highlights the role for STING in human disease where variants of the STING proteins, as well as dysregulated STING signalling, have been implicated in a number of inflammatory diseases. This review will summarise the recent structural and functional findings of STING, and discuss how STING research has promoted the development of novel therapeutic approaches and experimental tools to improve treatment of tumour and autoimmune diseases

Public Exposure by Natural Radionuclides in Drinking Water - Models for Effective Dose Assessment and Implications to Guidelines

In Austria the legal framework to ¿Exposure by natural radionuclides in drinking water¿ is the Austrian Drinking Water Ordinance (Trinkwasserverordnung BGBl. II 304/2001) which implements exactly the European Drinking Water Directive 98/83/EC. The minimum requirements on the quality of drinking water and water intended for human consumption are appointed in it. For radioactivity two indicative standard parameter limits are established ¿ tritium activity concentration of 100 Bq/l and total indicative dose TID (effective dose from radionuclides in drinking water except 3H, 40K, radon and radon progenies) of 0.1 mSv/a. The appointment and the evaluation of the TID are specified in the Austrian Standard OENORM S 5251:2005. Generally only the radionuclides 226Ra and 228Ra, dose conversion factors for adults and a yearly water consumption of 730 l are taken into account for dose calculation. In the paper the estimation of the TID according to the drinking water directive and the OENORM standard is compared to dose estimations for other age groups and other nuclides based on measurements carried out in Upper Austria. The dose contributions of 210Po and 210Pb clearly preponderate the dose contributions of the radium isotopes. An alternative model for dose estimations has been developed, which takes into account a daily water intake and a continuous excretion of activity from the body. The presented dose assessment clearly yields lower annual effective doses for the population. Present regulations and guidelines for drinking water monitoring and surveillance are discussed and evaluated with regard to the results of this study. Disagreement persists on methods and applied parameters for estimating total doses caused by natural radionuclides in drinking water within Europe, its individual countries and experts. This paper contributes supporting facts and feasibilities to yield a good basis for future guidelines.JRC.DDG.H.4-Transport and air qualit

Preface to ICRM2011 - Proceedings of the 18th International Conference on Radionuclide Metrology and its Applications

This preface to the Proceedings volume summarizes the objectives and outcomes of the conference ICRM 2011, and gives additional information on the working of the International Committee for Radionuclide Metrology.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Assessment of the uncertainty budget associated with 4pi-gamma counting

The 4pig-counting technique is recognized as a powerful primary method for the standardization of radionuclides decaying with abundant gamma emissions. Based on the use of a gamma detector in quasi 4pi-geometry, a detection efficiency close to 100% and a low uncertainty can be achieved thanks to the summing effect of subsequent gamma transitions. Uncertainties have to be assigned to the realistic modelling of the source-detector geometry with respect to dimensions, density and material composition, the calculation of the total counting efficiency of the detector for the various emitted radiation and the effect of possible flaws in the decay scheme of a radionuclide on the calculated total efficiency. Other uncertainty factors pertain to typical metrological sources of uncertainty, such as weighing, nuclear counting with pulse pile-up and system dead-time effects, impurity corrections, decay corrections, timing and frequency, etc. In order to ensure good metrological practices at NMIs, the uncertainties particular to the method are discussed.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Automating transition functions: a way to improve trading profits with recurrent reinforcement learning

This paper presents an application of the logistic smooth transition function and recurrent reinforcement learning for designing financial trading systems. We propose a trading system which is an upgraded version of the regime-switching recurrent reinforcement learning (RS-RRL) trading system referred to in the literature. In our proposed system (RS-RRL 2.0), we use an automated transition function to model the regime switches in equity returns. Unlike the original RS-RRL trading system, the dynamic of the transition function in our trading system is driven by utility maximization, which is in line with the trading purpose. Volume, relative strength index, price-to-earnings ratio, moving average prices from technical analysis, and the conditional volatility from a GARCH model are considered as possible options for the transition variable in RS-RRL type trading systems. The significance of Sharpe ratios, the choice of transition variables, and the stability of the trading system are examined by using the daily data of 20 Swiss SPI stocks for the period April 2009 to September 2013. The results from our experiment show that our proposed trading system outperforms the original RS-RRL and RRL trading systems suggested in the literature in terms of better Sharpe ratios recorded in three consecutive out-of-sample periods