Quantifying simulator discrepancy in discrete-time dynamical simulators

When making predictions with complex simulators it can be important to quantify the various sources of uncertainty. Errors in the structural specification of the simulator, for example due to missing processes or incorrect mathematical specification, can be a major source of uncertainty, but are often ignored. We introduce a methodology for inferring the discrepancy between the simulator and the system in discrete-time dynamical simulators. We assume a structural form for the discrepancy function, and show how to infer the maximum-likelihood parameter estimates using a particle filter embedded within a Monte Carlo expectation maximization (MCEM) algorithm. We illustrate the method on a conceptual rainfall-runoff simulator (logSPM) used to model the Abercrombie catchment in Australia. We assess the simulator and discrepancy model on the basis of their predictive performance using proper scoring rules. This article has supplementary material online

Mendeley reader counts for US computer science conference papers and journal articles

© 2020 The Authors. Published by MIT Press. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://direct.mit.edu/qss/article/1/1/347/15566/Mendeley-reader-counts-for-US-computer-scienceAlthough bibliometrics are normally applied to journal articles when used to support research evaluations, conference papers are at least as important in fast-moving computingrelated fields. It is therefore important to assess the relative advantages of citations and altmetrics for computing conference papers to make an informed decision about which, if any, to use. This paper compares Scopus citations with Mendeley reader counts for conference papers and journal articles that were published between 1996 and 2018 in 11 computing fields and had at least one US author. The data showed high correlations between Scopus citation counts and Mendeley reader counts in all fields and most years, but with few Mendeley readers for older conference papers and few Scopus citations for new conference papers and journal articles. The results therefore suggest that Mendeley reader counts have a substantial advantage over citation counts for recently-published conference papers due to their greater speed, but are unsuitable for older conference papers

The docking of synaptic vesicles on the presynaptic membrane induced by α-synuclein is modulated by lipid composition

α-Synuclein (αS) is a presynaptic disordered protein whose aberrant aggregation is associated with Parkinson’s disease. The functional role of αS is still debated, although it has been involved in the regulation of neurotransmitter release via the interaction with synaptic vesicles (SVs). We report here a detailed characterisation of the conformational properties of αS bound to the inner and outer leaflets of the presynaptic plasma membrane (PM), using small unilamellar vesicles. Our results suggest that αS preferentially binds the inner PM leaflet. On the basis of these studies we characterise in vitro a mechanism by which αS stabilises, in a concentration-dependent manner, the docking of SVs on the PM by establishing a dynamic link between the two membranes. The study then provides evidence that changes in the lipid composition of the PM, typically associated with neurodegenerative diseases, alter the modes of binding of αS, specifically in a segment of the sequence overlapping with the non-amyloid component region. Taken together, these results reveal how lipid composition modulates the interaction of αS with the PM and underlie its functional and pathological behaviours in vitro

The docking of synaptic vesicles on the presynaptic membrane induced by α-synuclein is modulated by lipid composition

α-Synuclein (αS) is a presynaptic disordered protein whose aberrant aggregation is associated with Parkinson’s disease. The functional role of αS is still debated, although it has been involved in the regulation of neurotransmitter release via the interaction with synaptic vesicles (SVs). We report here a detailed characterisation of the conformational properties of αS bound to the inner and outer leaflets of the presynaptic plasma membrane (PM), using small unilamellar vesicles. Our results suggest that αS preferentially binds the inner PM leaflet. On the basis of these studies we characterise in vitro a mechanism by which αS stabilises, in a concentration-dependent manner, the docking of SVs on the PM by establishing a dynamic link between the two membranes. The study then provides evidence that changes in the lipid composition of the PM, typically associated with neurodegenerative diseases, alter the modes of binding of αS, specifically in a segment of the sequence overlapping with the non-amyloid component region. Taken together, these results reveal how lipid composition modulates the interaction of αS with the PM and underlie its functional and pathological behaviours in vitro