Quantifying similarity of pore-geometry in nanoporous materials

In most applications of nanoporous materials the pore structure is as important as the chemical composition as a determinant of performance. For example, one can alter performance in applications like carbon capture or methane storage by orders of magnitude by only modifying the pore structure. For these applications it is therefore important to identify the optimal pore geometry and use this information to find similar materials. However, the mathematical language and tools to identify materials with similar pore structures, but different composition, has been lacking. We develop a pore recognition approach to quantify similarity of pore structures and classify them using topological data analysis. This allows us to identify materials with similar pore geometries, and to screen for materials that are similar to given top-performing structures. Using methane storage as a case study, we also show that materials can be divided into topologically distinct classes requiring different optimization strategies

Investigation of the key chemical structures involved in the anticancer activity of disulfiram in A549 non-small cell lung cancer cell line

© 2018 The Author(s). Background: Disulfiram (DS), an antialcoholism medicine, demonstrated strong anticancer activity in the laboratory but did not show promising results in clinical trials. The anticancer activity of DS is copper dependent. The reaction of DS and copper generates reactive oxygen species (ROS). After oral administration in the clinic, DS is enriched and quickly metabolised in the liver. The associated change of chemical structure may make the metabolites of DS lose its copper-chelating ability and disable their anticancer activity. The anticancer chemical structure of DS is still largely unknown. Elucidation of the relationship between the key chemical structure of DS and its anticancer activity will enable us to modify DS and speed its translation into cancer therapeutics. Methods: The cytotoxicity, extracellular ROS activity, apoptotic effect of DS, DDC and their analogues on cancer cells and cancer stem cells were examined in vitro by MTT assay, western blot, extracellular ROS assay and sphere-reforming assay. Results: Intact thiol groups are essential for the in vitro cytotoxicity of DS. S-methylated diethyldithiocarbamate (S-Me-DDC), one of the major metabolites of DS in liver, completely lost its in vitro anticancer activity. In vitro cytotoxicity of DS was also abolished when its thiuram structure was destroyed. In contrast, modification of the ethyl groups in DS had no significant influence on its anticancer activity. Conclusions: The thiol groups and thiuram structure are indispensable for the anticancer activity of DS. The liver enrichment and metabolism may be the major obstruction for application of DS in cancer treatment. A delivery system to protect the thiol groups and development of novel soluble copper-DDC compound may pave the path for translation of DS into cancer therapeutics.This work was supported by grant from British Lung Foundation (RG14–8) and Innovate UK (104022).Published versio

Chronic toxicity effects of ZnSO4and ZnO nanoparticles in Daphnia magna

The chronic toxicity of ZnSO4 and ZnO nanoparticles has been studied in Daphnia magna also considering the life cycle parameters beyond the standard 21-day exposure time. Specimens have been individually followed until the natural end of their life, and some of them sampled for microscopic analyses at 48h, 9 and 21 days. Despite the low level of exposure (0.3mg Zn/L), ultrastructural analyses of the midgut epithelial cells revealed efficient internalization of nanoparticles between 48h and 9d, and translocation to other tissues as well. At 21d, the most affected fields have been recorded for both compounds; in particular samples exposed to ZnO nanoparticles showed swelling of mitochondria, while those exposed to ZnSO4 had a great number of autophagy vacuoles. The life cycle parameters resulted altered as well, with a significant inhibition of reproduction in both groups, when compared to controls. After the 21-day exposure, some interesting results were obtained: animals, previously exposed to nanoZnO at low concentrations, showed a complete recovery of the full reproduction potential, while those previously exposed to ZnSO4 presented a dose-dependent and compound-specific reduction in lifespan. Based on the results from the present research and the effects of the same chemicals at higher doses, it can be concluded that the soluble form plays a key role in ZnO nanoparticle cytotoxicity, and that the nanoparticulate form is able to locally increase the amount of Zn inside the cell, even within the ovary. It's worth noting that ZnO nanoparticles have been internalized despite the very low concentration used: this raises concern about the possible environmental implications which may derive from their use, and which in turn must be carefully considered

Prospective severity classification of scientific procedures in cephalopods: Report of a COST FA1301 Working Group Survey

Cephalopods are the first invertebrate class regulated by the European Union under Directive 2010/63/EU on the protection of animals used for scientific purposes, which requires prospective assessment of severity of procedures. To assist the scientific community in establishing severity classification for cephalopods we undertook a web-based survey of the EU cephalopod research community as represented by the participants in the COST Action FA1301-CephsInAction. The survey consisted of 50 scenarios covering a range of procedures involving several cephalopod species at different life-stages. Respondents (59 people from 15 countries) allocated a severity classification to each scenario, or indicated that they were unable to decide (UTD). Analyses evaluated score distributions and clustering. Overall, the UTD scores were low (7.0 ± 0.6%) and did not affect the severity classification. Procedures involving paralarvae and killing methods (not specified in Annexe IV) had the highest UTD scores. Consensus on non-recovery procedures was reached consistently, although occasionally non-recovery appeared to be confused with killing methods. Scenarios describing procedures above the ‘lower threshold’ for regulation, including those describing behavioural studies, were also identified and allocated throughout the full range of severity classifications. Severity classification for scenarios based on different species (e.g., cuttlefish vs. octopus) was consistent, comparable and dependent on potentially more harmful interventions. We found no marked or statistically significant differences in the overall scoring of scenarios between the demographic sub-groups (age, gender, PhD, cephalopod experience). The COST Action FA1301 survey data provides a basis for a prospective severity classification for cephalopods to serve as guide for researchers, project assessors and regulators