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In vitro to in vivo extrapolation represents a critical challenge in toxicology. In this paper we explore extrapolation strategies for acetaminophen (APAP) based on mechanistic models, comparing classical (CL) homogeneous compartment pharmacodynamic (PD) models and a spatial-temporal (ST), multiscale digital twin model resolving liver microarchitecture at cellular resolution. The models integrate consensus detoxification reactions in each individual hepatocyte. We study the consequences of the two model types on the extrapolation and show in which cases these models perform better than the classical extrapolation strategy that is based either on the maximal drug concentration (Cmax) or the area under the pharmacokinetic curve (AUC) of the drug blood concentration. We find that an CL-model based on a well-mixed blood compartment is sufficient to correctly predict the in vivo toxicity from in vitro data. However, the ST-model that integrates more experimental information requires a change of at least one parameter to obtain the same prediction, indicating that spatial compartmentalization may indeed be an important factor.

A phytochemical investigation of the liana of Artabotrys thomsonii led to the isolation of a new oxoberberine alkaloid, 2,10-dihydroxy-3,9-dimethoxy-8-oxo-protoberberine (7), along with six known compounds. Their chemical structures were elucidated by 1 D and 2 D NMR spectroscopic methods and HRESI-MSn data analysis. Compounds 4 and 7 were selected for further in vitro investigations. In accordance with expectations from their chemical structures, compounds 7 and 4 showed a clear antioxidant activity in a cell-free assay, with compound 7 being 7-fold more active than 4. Cytotoxicity, cytostatic and genotoxic effects only occurred at high micromolar concentrations of 50 µM or more. Compound 7 was slightly less effective than compound 4. A low micromolar concentration of 10 µM did not cause any damaging cellular effects but showed potential for a protection against the micronucleus-inducing effect of reactive oxygen species hydrogen peroxide, although not to a significant extent.

International audience; The immune system of bees is influenced by a diversity of factors, some of which have changed in the last 10 years such as the application of pesticides. In addition to pollen, nectar and dust, guttated water of seed-dressed plants might be a new source of contamination to bees. Our experiments demonstrated that guttated water of plants germinated from seeds dressed with neonicotinoids contains neonicotinoids. Maize seeds treated with clothianidin (Poncho® 0.5 mg/seed and Poncho® Pro 1.25 mg/seed) resulted in neonicotinoid concentrations up to 8,000 ng mL−1 in the guttated fluid. This concentration decreases rapidly, but remained detectable over several weeks. Seeds treated with Poncho® Pro did not result in higher concentrations in guttated droplets in the first stages of plant development, but the concentration decreased more slowly. Triticale seed treated with imidacloprid contained small quantities of this active agent (up to 13 ng mL−1) in the guttated fluid the following spring after overwintering. During the sampling of guttation fluid, no bees were observed collecting these droplets from triticale or maize. To evaluate the attractiveness of guttation fluid exuded from seed-treated plants under field conditions, more studies are required.

The findings of the EU ‘Materials Assessment Group’ (MAG), within the 2012 EU Fusion Roadmap exercise, are discussed. MAG analysed the technological readiness of structural, plasma facing and high heat flux materials for a DEMO concept to be constructed in the early 2030s, proposing a coherent strategy for R&D up to a DEMO construction decision.A DEMO phase I with a ‘Starter Blanket’ and ‘Starter Divertor’ is foreseen: the blanket being capable of withstanding ⩾2 MW yr m−2 fusion neutron fluence (∼20 dpa in the front-wall steel). A second phase ensues for DEMO with ⩾5 MW yr m−2 first wall neutron fluence. Technical consequences for the materials required and the development, testing and modelling programmes, are analysed using: a systems engineering approach, considering reactor operational cycles, efficient maintenance and inspection requirements, and interaction with functional materials/coolants; and a project-based risk analysis, with R&D to mitigate risks from material shortcomings including development of specific risk mitigation materials. The DEMO balance of plant constrains the blanket and divertor coolants to remain unchanged between the two phases. The blanket coolant choices (He gas or pressurised water) put technical constraints on the blanket steels, either to have high strength at higher temperatures than current baseline variants (above 650 °C for high thermodynamic efficiency from He-gas coolant), or superior radiation-embrittlement properties at lower temperatures (∼290–320 °C), for construction of water-cooled blankets. Risk mitigation proposed would develop these options in parallel, and computational and modelling techniques to shorten the cycle-time of new steel development will be important to achieve tight R&D timescales. The superior power handling of a water-cooled divertor target suggests a substructure temperature operating window (∼200–350 °C) that could be realised, as a baseline-concept, using tungsten on a copper-alloy substructure. The difficulty of establishing design codes for brittle tungsten puts great urgency on the development of a range of advanced ductile or strengthened tungsten and copper compounds.Lessons learned from Fission reactor material development have been included, especially in safety and licensing, fabrication/joining techniques and designing for in-vessel inspection. The technical basis of using the ITER licensing experience to refine the issues in nuclear testing of materials is discussed.Testing with 14 MeV neutrons is essential to Fusion Materials development, and the Roadmap requires acquisition of ⩾30 dpa (steels) 14 MeV test data by 2026. The value and limits of pre-screening testing with fission neutrons on isotopically- or chemically-doped steels and with ion-beams are evaluated to help determine the minimum14 MeV testing programme requirements.