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Year of publication
- 2014 (102) (remove)
Document Type
- Postprint (102) (remove)
Is part of the Bibliography
- yes (102) (remove)
Keywords
- anomalous diffusion (5)
- living cells (4)
- Cardiac rehabilitation (2)
- RPA (2)
- acquisition (2)
- ancient DNA (2)
- arsenolipids present (2)
- behavior (2)
- cod-liver (2)
- damage (2)
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- Institut für Chemie (32)
- Mathematisch-Naturwissenschaftliche Fakultät (17)
- Humanwissenschaftliche Fakultät (14)
- Institut für Biochemie und Biologie (9)
- Institut für Physik und Astronomie (6)
- Institut für Anglistik und Amerikanistik (5)
- Department Sport- und Gesundheitswissenschaften (4)
- Institut für Germanistik (3)
- Philosophische Fakultät (3)
- Wirtschafts- und Sozialwissenschaftliche Fakultät (2)
Pieper, Imke ; Wehe, Christoph A. ; Bornhorst, Julia ; Ebert, Franziska ; Leffers, Larissa ; Holtkamp, Michael ; Höseler, Pia ; Weber, Till ; Mangerich, Aswin ; Bürkle, Alexander ; Karst, Uwe ; Schwerdtle, Tanja
The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co- genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl) ation contributes to organic Hg induced neurotoxicity.
claspfolio 2
(2014)
Building on the award-winning, portfolio-based ASP solver claspfolio, we present claspfolio 2, a modular and open solver architecture that integrates several different portfolio-based algorithm selection approaches and techniques. The claspfolio 2 solver framework supports various feature generators, solver selection approaches, solver portfolios, as well as solver-schedule-based pre-solving techniques. The default configuration of claspfolio 2 relies on a light-weight version of the ASP solver clasp to generate static and dynamic instance features. The flexible open design of claspfolio 2 is a distinguishing factor even beyond ASP. As such, it provides a unique framework for comparing and combining existing portfolio-based algorithm selection approaches and techniques in a single, unified framework. Taking advantage of this, we conducted an extensive experimental study to assess the impact of different feature sets, selection approaches and base solver portfolios. In addition to gaining substantial insights into the utility of the various approaches and techniques, we identified a default configuration of claspfolio 2 that achieves substantial performance gains not only over clasp's default configuration and the earlier version of claspfolio, but also over manually tuned configurations of clasp.