Shingle 2.0: generalising self-consistent and automated domain discretisation for multi-scale geophysical models

The approaches taken to describe and develop spatial discretisations of the domains required for geophysical simulation models are commonly ad hoc, model or application specific and under-documented. This is particularly acute for simulation models that are flexible in their use of multi-scale, anisotropic, fully unstructured meshes where a relatively large number of heterogeneous parameters are required to constrain their full description. As a consequence, it can be difficult to reproduce simulations, ensure a provenance in model data handling and initialisation, and a challenge to conduct model intercomparisons rigorously. This paper takes a novel approach to spatial discretisation, considering it much like a numerical simulation model problem of its own. It introduces a generalised, extensible, self-documenting approach to carefully describe, and necessarily fully, the constraints over the heterogeneous parameter space that determine how a domain is spatially discretised. This additionally provides a method to accurately record these constraints, using high-level natural language based abstractions, that enables full accounts of provenance, sharing and distribution. Together with this description, a generalised consistent approach to unstructured mesh generation for geophysical models is developed, that is automated, robust and repeatable, quick-to-draft, rigorously verified and consistent to the source data throughout. This interprets the description above to execute a self-consistent spatial discretisation process, which is automatically validated to expected discrete characteristics and metrics.Comment: 18 pages, 10 figures, 1 table. Submitted for publication and under revie

Does current UK research address priorities in palliative and end-of-life care?

The Palliative and end of life care Priority Setting Partnership uncovered 83 unanswered research questions. Florence Todd Fordham, Bridget Candy, Stevie McMillan and Sabine Best show that, as current UK research starts to address some of these questions, UK open grant data have the potential to encourage collaboratio

Altered Cerebellar Short-Term Plasticity but No Change in Postsynaptic AMPA-Type Glutamate Receptors in a Mouse Model of Juvenile Batten Disease

Juvenile Batten disease is the most common progressive neurodegenerative disorder of childhood. It is associated with mutations in the CLN3 gene, causing loss of function of CLN3 protein and degeneration of cerebellar and retinal neurons. It has been proposed that changes in granule cell AMPA-type glutamate receptors (AMPARs) contribute to the cerebellar dysfunction. In this study we compared AMPAR properties and synaptic transmission in cerebellar granule cells from wild-type and Cln3 knockout mice. In Cln3Δex1–6 cells the amplitude of AMPA-evoked whole-cell currents was unchanged. Similarly, we found no change in the amplitude, kinetics, or rectification of synaptic currents evoked by individual quanta, or in their underlying single-channel conductance. We found no change in cerebellar expression of GluA2 or GluA4 protein. By contrast, we observed a reduced number of quantal events following mossy-fiber stimulation in Sr2+, altered short-term plasticity in conditions of reduced extracellular Ca2+, and reduced mossy fiber vesicle number. Thus, while our results suggest early presynaptic changes in the Cln3Δex1–6 mouse model of juvenile Batten disease, they reveal no evidence for altered postsynaptic AMPARs

Functional interplay between NTP leaving group and base pair recognition during RNA polymerase II nucleotide incorporation revealed by methylene substitution.

RNA polymerase II (pol II) utilizes a complex interaction network to select and incorporate correct nucleoside triphosphate (NTP) substrates with high efficiency and fidelity. Our previous 'synthetic nucleic acid substitution' strategy has been successfully applied in dissecting the function of nucleic acid moieties in pol II transcription. However, how the triphosphate moiety of substrate influences the rate of P-O bond cleavage and formation during nucleotide incorporation is still unclear. Here, by employing β,γ-bridging atom-'substituted' NTPs, we elucidate how the methylene substitution in the pyrophosphate leaving group affects cognate and non-cognate nucleotide incorporation. Intriguingly, the effect of the β,γ-methylene substitution on the non-cognate UTP/dT scaffold (∼3-fold decrease in kpol) is significantly different from that of the cognate ATP/dT scaffold (∼130-fold decrease in kpol). Removal of the wobble hydrogen bonds in U:dT recovers a strong response to methylene substitution of UTP. Our kinetic and modeling studies are consistent with a unique altered transition state for bond formation and cleavage for UTP/dT incorporation compared with ATP/dT incorporation. Collectively, our data reveals the functional interplay between NTP triphosphate moiety and base pair hydrogen bonding recognition during nucleotide incorporation

An Enhanced Nonlinear Critical Gradient for Electron Turbulent Transport due to Reversed Magnetic Shear

The first nonlinear gyrokinetic simulations of electron internal transport barriers (e-ITBs) in the National Spherical Torus Experiment show that reversed magnetic shear can suppress thermal transport by increasing the nonlinear critical gradient for electron-temperature-gradient-driven turbulence to three times its linear critical value. An interesting feature of this turbulence is nonlinearly driven off-midplane radial streamers. This work reinforces the experimental observation that magnetic shear is likely an effective way of triggering and sustaining e-ITBs in magnetic fusion devices.Comment: 4 pages, 5 figure

An Enhanced Nonlinear Critical Gradient for Electron Turbulent Transport due to Reversed Magnetic Shear

The first nonlinear gyrokinetic simulations of electron internal transport barriers (e-ITBs) in the National Spherical Torus Experiment show that reversed magnetic shear can suppress thermal transport by increasing the nonlinear critical gradient for electron-temperature-gradient-driven turbulence to three times its linear critical value. An interesting feature of this turbulence is nonlinearly driven off-midplane radial streamers. This work reinforces the experimental observation that magnetic shear is likely an effective way of triggering and sustaining e-ITBs in magnetic fusion devices.Comment: 4 pages, 5 figure

Acid-sensing ion channel 1a drives AMPA receptor plasticity following ischemia and acidosis in hippocampal CA1 neurons

The CA1 region of the hippocampus is particularly vulnerable to ischemic damage. While NMDA receptors play a major role in excitotoxicity, it is thought to be exacerbated in this region by two forms of post-ischemic AMPA receptor (AMPAR) plasticity - namely, anoxic long-term potentiation (a-LTP), and a delayed increase in the prevalence of Ca2+ -permeable GluA2-lacking AMPARs (CP-AMPARs). The acid-sensing ion channel 1a (ASIC1a) which is expressed in CA1 pyramidal neurons, is also known to contribute to post-ischemic neuronal death and to physiologically induced LTP. This raises the question - does ASIC1a activation drive the post-ischemic forms of AMPAR plasticity in CA1 pyramidal neurons? We have tested this by examining organotypic hippocampal slice cultures (OHSCs) exposed to oxygen glucose deprivation (OGD), and dissociated cultures of hippocampal pyramidal neurons (HPN) exposed to low pH (acidosis). We find that both a-LTP and the delayed increase in the prevalence of CP-AMPARs are dependent on ASIC1a activation during ischemia. Indeed, acidosis alone is sufficient to induce the increase in CP-AMPARs. We also find that inhibition of ASIC1a channels circumvents any potential neuroprotective benefit arising from block of CP-AMPARs. By demonstrating that ASIC1a activation contributes to post-ischemic AMPAR plasticity, our results identify a functional interaction between acidotoxicity and excitotoxicity in hippocampal CA1 cells, and provide insight into the role of ASIC1a and CP-AMPARs as potential drug targets for neuroprotection. We thus propose that ASIC1a activation can drive certain forms of CP-AMPAR plasticity, and that inhibiting ASIC1a affords neuroprotection

Efficient unstructured mesh generation for marine renewable energy applications

Renewable energy is the cornerstone of preventing dangerous climate change whilst maintaining a robust energy supply. Tidal energy will arguably play a critical role in the renewable energy portfolio as it is both predictable and reliable, and can be put in place across the globe. However, installation may impact the local and regional ecology via changes in tidal dynamics, sediment transport pathways or bathymetric changes. In order to mitigate these effects, tidal energy devices need to be modelled in order to predict hydrodynamic changes. Robust mesh generation is a fundamental component required for developing simulations with high accuracy. However, mesh generation for coastal domains can be an elaborate procedure. Here, we describe an approach combining mesh generators with Geographical Information Systems. We demonstrate robustness and efficiency by constructing a mesh with which to examine the potential environmental impact of a tidal turbine farm installation in the Orkney Islands. The mesh is then used with two well-validated ocean models, to compare their flow predictions with and without a turbine array. The results demonstrate that it is possible to create an easy-to-use tool to generate high-quality meshes for combined coastal engineering, here tidal turbines, and coastal ocean simulations

Middle and Late Pleistocene environmental history of the Marsworth area, south-central England

To elucidate the Middle and Late Pleistocene environmental history of south-central England, we report the stratigraphy, sedimentology, palaeoecology and geochronology of some deposits near the foot of the Chiltern Hills scarp at Marsworth, Buckinghamshire. The Marsworth site is important because its sedimentary sequences contain a rich record of warm stages and cold stages, and it lies close to the Anglian glacial limit. Critical to its history are the origin and age of a brown pebbly silty clay (diamicton) previously interpreted as weathered till. The deposits described infill a river channel incised into chalk bedrock. They comprise clayey, silty and gravelly sediments, many containing locally derived chalk and some with molluscan, ostracod and vertebrate remains. Most of the deposits are readily attributed to periglacial and fluvial processes, and some are dated by optically stimulated luminescence to Marine Isotope Stage (MIS) 6. Although our sedimentological data do not discriminate between a glacial or periglacial interpretation of the diamicton, amino-acid dating of three molluscan taxa from beneath it indicates that it is younger than MIS 9 and older than MIS 5e. This makes a glacial interpretation unlikely, and we interpret the diamicton as a periglacial slope deposit. The Pleistocene history reconstructed for Marsworth identifies four key elements: (1) Anglian glaciation during MIS 12 closely approached Marsworth, introducing far-travelled pebbles such as Rhaxella chert and possibly some fine sand minerals into the area. (2) Interglacial environments inferred from fluvial sediments during MIS 7 varied from fully interglacial conditions during sub-stages 7e and 7c, cool temperate conditions during sub-stage 7b or 7a, temperate conditions similar to those today in central England towards the end of the interglacial, and cool temperate conditions during sub-stage 7a. (3) Periglacial activity during MIS 6 involved thermal contraction cracking, permafrost development, fracturing of chalk bedrock, fluvial activity, slopewash, mass movement and deposition of loess and coversand. (4) Fully interglacial conditions during sub-stage 5e led to renewed fluvial activity, soil formation and acidic weathering