Water, energy, food, land and climate form a tightly-connected nexus in which actions on one sector impact other sectors, creating feedbacks and unanticipated consequences. This is especially because at present, much scientific research and many policies are constrained to single discipline/sector silos that are often not interacting (e.g., water-related research/policy). However, experimenting with the interaction and determining how a change in one sector could impact another may require unreasonable time frames, be very difficult in practice and may be potentially dangerous, triggering any one of a number of unanticipated side-effects. Current modelling often neglects knowledge from practice. Therefore, a safe environment is required to test the potential cross-sectoral implications of policy decisions in one sector on other sectors. Serious games offer such an environment by creating realistic 'simulations', where long-term impacts of policies may be tested and rated. This paper describes how the ongoing (2016-2020) Horizon2020 project SIM4NEXUS will develop serious games investigating potential plausible cross-nexus implications and synergies due to policy interventions for 12 multi-scale case studies ranging from regional to global. What sets these games apart is that stakeholders and partners are involved in all aspects of the modelling definition and process, from case study conceptualisation, quantitative model development including the implementation and validation of each serious game. Learning from playing a serious game is justified by adopting a proof-of-concept for a specific regional case study in Sardinia (Italy). The value of multi-stakeholder involvement is demonstrated, and critical lessons learned for serious game development in general are presented.
The synthesis of six novel cyclometallated platinum(iv) iodido complexes is accomplished by intermolecular oxidative addition of methyl iodide (compounds 2a-2c) or iodine (compounds 3a-3c) upon cyclometallated platinum(ii) compounds [PtX{(CH)N(CH)NCH(4-ClCH)}] (1a-1c: X = Cl, CH or I). The X-ray molecular structures of platinum(ii) compound 1c and platinum(iv) compounds 3b and 3a' (an isomer of 3a) are reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), DNA interaction, topoisomerase I, IIα, and cathepsin B inhibition, and cell cycle arrest, apoptosis and ROS generation of the investigated complexes are presented. Remarkable antiproliferative activity was observed for most of the synthesized cycloplatinated compounds (series 1-3) in all the selected carcinoma cell lines. The best inhibition was provided for the octahedral platinum(iv) compounds 2a-2c exhibiting a methyl and an iodido axial ligand. Preliminary biological results point to a different mechanism of action for the investigated compounds. Cyclometallated platinum(ii) compounds 1a-1c modify the DNA migration as cisplatin. In contrast, cyclometallated platinum(iv) compounds 2a-2c and 3a-3c did not modify the DNA tertiary structure neither in the absence nor in the presence of ascorbic acid, which made them incapable of reducing platinum(iv) compounds 2b and 2c in a buffered aqueous medium (pH 7.40) according to H NMR experiments. Remarkable topoisomerase IIα inhibitory activity is reported for platinum(iv) complexes 2b and 3a and in addition, for the last one, a moderate cathepsin B inhibition is reported. Cell cycle arrest (decrease in G0/G1 and G2 phases and arrest in the S phase), induction of apoptosis and ROS generation are related to the antiproliferative activity of some representative octahedral cyclometallated platinum(iv) compounds (2b and 2c).
Wastewater-based epidemiology has shown to be an efficient tool to track the circulation of SARS-CoV-2 in communities assisted by wastewater treatment plants (WWTPs). The challenge comes when this approach is employed to help Health authorities in their decision-making. Here, we describe the roadmap for the design and deployment of SARSAIGUA, the Catalan Surveillance Network of SARS-CoV-2 in Sewage. The network monitors, weekly or biweekly, 56 WWTPs evenly distributed across the territory and serving 6 M inhabitants (80% of the Catalan population). Each week, samples from 45 WWTPs are collected, analyzed, results reported to Health authorities, and finally published within less than 72 h in an online dashboard (https://sarsaigua.icra.cat). After 20 months of monitoring (July 20–March 22), the standardized viral load (gene copies/day) in all the WWTPs monitored fairly matched the cumulative number of COVID-19 cases along the successive pandemic waves, showing a good fit with the diagnosed cases in the served municipalities (Spearman Rho = 0.69). Here we describe the roadmap of the design and deployment of SARSAIGUA while providing several open-access tools for the management and visualization of the surveillance data.
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