Assessing urban strategies for reducing the impacts of extreme weather on infrastructure networks

Critical infrastructure networks, including transport, are crucial to the social and economic function of urban areas but are at increasing risk from natural hazards. Minimizing disruption to these networks should form part of a strategy to increase urban resilience. A framework for assessing the disruption from flood events to transport systems is presented that couples a high-resolution urban flood model with transport modelling and network analytics to assess the impacts of extreme rainfall events, and to quantify the resilience value of different adaptation options. A case study in Newcastle upon Tyne in the UK shows that both green roof infrastructure and traditional engineering interventions such as culverts or flood walls can reduce transport disruption from flooding. The magnitude of these benefits depends on the flood event and adaptation strategy, but for the scenarios considered here 3–22% improvements in city-wide travel times are achieved. The network metric of betweenness centrality, weighted by travel time, is shown to provide a rapid approach to identify and prioritize the most critical locations for flood risk management intervention. Protecting just the top ranked critical location from flooding provides an 11% reduction in person delays. A city-wide deployment of green roofs achieves a 26% reduction, and although key routes still flood, the benefits of this strategy are more evenly distributed across the transport network as flood depths are reduced across the model domain. Both options should form part of an urban flood risk management strategy, but this method can be used to optimize investment and target limited resources at critical locations, enabling green infrastructure strategies to be gradually implemented over the longer term to provide city-wide benefits. This framework provides a means of prioritizing limited financial resources to improve resilience. This is particularly important as flood management investments must typically exceed a far higher benefit–cost threshold than transport infrastructure investments. By capturing the value to the transport network from flood management interventions, it is possible to create new business models that provide benefits to, and enhance the resilience of, both transport and flood risk management infrastructures. Further work will develop the framework to consider other hazards and infrastructure networks

Density functional theory studies of MTSL nitroxide side chain conformations attached to an activation loop

A quantum-mechanical (QM) method rooted on density functional theory (DFT) linked to the Stochastic Liouville equation (SLE) in the Fokker Planck (FP) form has been employed for the first time to sample the methane-thiosulfonate spin label (MTSL) conformational space attached to the Aurora-A kinase activation loop and to calculate the EPR spectrum. The features of the calculated energy surface allowed us to describe the system in a limited number of rotamers stabilized by interactions of the MTSL side chain and neighbouring residues. The relevant magnetic parameters and the electron paramagnetic resonance (EPR) spectrum were subsequently calculated from the trajectories of the spin probe in the protein environment. The comparison between theoretical and experimental continuous wave (CW) EPR spectra revealed some small differences in the EPR line shape which arises from the combinations of g- and A-values obtained from the conformations selected. The theoretical approach adopted in this work can be used to recognise the contribution of MTSL rotamers to the EPR spectrum in order to help extract structural/dynamics properties of protein from the experimental data

Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2

Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilized pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID-19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in-house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterized samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries