Superposition-Enhanced Estimation of Optimal Temperature Spacings for Parallel Tempering Simulations.

Effective parallel tempering simulations rely crucially on a properly chosen sequence of temperatures. While it is desirable to achieve a uniform exchange acceptance rate across neighboring replicas, finding a set of temperatures that achieves this end is often a difficult task, in particular for systems undergoing phase transitions. Here we present a method for determination of optimal replica spacings, which is based upon knowledge of local minima in the potential energy landscape. Working within the harmonic superposition approximation, we derive an analytic expression for the parallel tempering acceptance rate as a function of the replica temperatures. For a particular system and a given database of minima, we show how this expression can be used to determine optimal temperatures that achieve a desired uniform acceptance rate. We test our strategy for two atomic clusters that exhibit broken ergodicity, demonstrating that our method achieves uniform acceptance as well as significant efficiency gains.This project was funded by EPSRC Grant EP/I001352/1 and the ERC

Novel low energy hydrogen–deuterium isotope breakthrough separation using a trapdoor zeolite

AbstractCs-chabazite, a type of zeolite with caesium counter-cations, possesses interesting gas separation properties due to a highly selective molecular “trapdoor” effect. Herein the use of this material for H2/D2 isotope separation is demonstrated. Isotope separation was achieved using breakthrough separation with a single pass through a packed bed at moderate temperatures (293K) and pressures (0.17MPa) when one species was in a sufficiently low concentration. The breakthrough separation curves were successfully modelled using the Thomas kinetic breakthrough model and the Yoon and Nelson kinetic breakthrough model, where working transferable kinetic rate constants were developed. Use of this material for hydrogen isotope separation would significantly lower the total energy demand compared with current hydrogen isotope separation techniques such as cryogenic distillation and is applicable to separating out low concentrations of D2 (0.0156%) present in standard grade H2

Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles: synthesis, antibacterial evaluation and preliminary mechanism of action studies

Synthetic small molecular antimicrobial peptidomimetics represent a promising new class of potential antibiotics due to their membrane-disrupting ability and their decreased propensity for bacterial resistance. A library of 43 mono- and di-cationic biaryl 1,2,3-triazolyl peptidomimetics was designed and synthesized based upon previously established lead biarylpeptidomimetics and a known pharmacophore. A reliable, facile and modular synthetic pathway allowed for the efficient synthesis of multiple unique scaffolds which were subjected to divergent derivatization to furnish the amphiphilic compounds. In vitro testing revealed enhanced antibacterial efficacy against a range of pathogenic bacteria, including bacterial isolates with methicillin, vancomycin, daptomycin, or multi-drug resistance. Preliminary time-kill kinetics and membrane-disruption assays revealed a likely membrane-active mechanism for the tested peptidomimetics. An optimal balance between hydrophobicity and cationic charge was found to be essential for reduced cytotoxicity/haemolysis (i.e. membrane selectivity) and enhanced Gram-negative activity. The cationic biaryl amphiphile 81 was identified as a potent, broad-spectrum peptidomimetic with activity against Gram-positive (methicillin-resistant Staphylococcus aureus - MIC = 2 μg/mL) and Gram-negative (Escherichia coli - MIC = 4 μg/mL) pathogenic bacteria

Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles: synthesis, antibacterial evaluation and preliminary mechanism of action studies

Synthetic small molecular antimicrobial peptidomimetics represent a promising new class of potential antibiotics due to their membrane-disrupting ability and their decreased propensity for bacterial resistance. A library of 43 mono- and di-cationic biaryl 1,2,3-triazolyl peptidomimetics was designed and synthesized based upon previously established lead biarylpeptidomimetics and a known pharmacophore. A reliable, facile and modular synthetic pathway allowed for the efficient synthesis of multiple unique scaffolds which were subjected to divergent derivatization to furnish the amphiphilic compounds. In vitro testing revealed enhanced antibacterial efficacy against a range of pathogenic bacteria, including bacterial isolates with methicillin, vancomycin, daptomycin, or multi-drug resistance. Preliminary time-kill kinetics and membrane-disruption assays revealed a likely membrane-active mechanism for the tested peptidomimetics. An optimal balance between hydrophobicity and cationic charge was found to be essential for reduced cytotoxicity/haemolysis (i.e. membrane selectivity) and enhanced Gram-negative activity. The cationic biaryl amphiphile 81 was identified as a potent, broad-spectrum peptidomimetic with activity against Gram-positive (methicillin-resistant Staphylococcus aureus - MIC = 2 μg/mL) and Gram-negative (Escherichia coli - MIC = 4 μg/mL) pathogenic bacteria. © 2019 Elsevier Masson SA

Equilibrium molecular thermodynamics from Kirkwood sampling.

We present two methods for barrierless equilibrium sampling of molecular systems based on the recently proposed Kirkwood method (J. Chem. Phys. 2009, 130, 134102). Kirkwood sampling employs low-order correlations among internal coordinates of a molecule for random (or non-Markovian) sampling of the high dimensional conformational space. This is a geometrical sampling method independent of the potential energy surface. The first method is a variant of biased Monte Carlo, where Kirkwood sampling is used for generating trial Monte Carlo moves. Using this method, equilibrium distributions corresponding to different temperatures and potential energy functions can be generated from a given set of low-order correlations. Since Kirkwood samples are generated independently, this method is ideally suited for massively parallel distributed computing. The second approach is a variant of reservoir replica exchange, where Kirkwood sampling is used to construct a reservoir of conformations, which exchanges conformations with the replicas performing equilibrium sampling corresponding to different thermodynamic states. Coupling with the Kirkwood reservoir enhances sampling by facilitating global jumps in the conformational space. The efficiency of both methods depends on the overlap of the Kirkwood distribution with the target equilibrium distribution. We present proof-of-concept results for a model nine-atom linear molecule and alanine dipeptide.This research was funded by the European Research Council and EPSRC grant EP/I001352/1. Y.O. was supported, in part, by the JSPS Grant-in-Aid for Scientific Research on Innovative Areas (“Dynamical Ordering and Integrated Functions”).This is the final published version. It first appeared at http://pubs.acs.org/doi/abs/10.1021/acs.jpcb.5b01800

A randomised controlled trial of laser scanning and casting for the construction of ankle foot orthoses

Study Design: Randomised controlled trial with blinding of orthotists and patients to the construction technique used. Background: Three-dimensional laser scanning has been used for patient measurement for cranial helmets and spinal braces. Ankle foot orthoses are commonly prescribed for children with orthopaedic conditions. This trial sought to compare ankle foot orthoses produced by laser scanning or traditional plaster casting. Objectives: Assessment of the effectiveness and efficiency of using laser scanning to produce AFOs. Methods: A randomised double blind trial comparing fabrication of AFOs from casts or laser scans. Results: The time spent in the rectification and moulding of scanned AFOs was around 50% less than for cast AFOs. A non-significant increase of 9 days was seen in the time to delivery to the patient for LSCAD/CAM. There was a higher incidence of problems with the scan-based AFOs at delivery of the device, but no difference in how long the AFOs lasted. Costs associated with laser scanning were not significantly different from traditional methods of AFO manufacture. Conclusions: Compared with conventional casting techniques laser scan based AFO manufacture neither significantly improved the quality of the final product nor delivered a useful saving in time

Gas sensing using porous materials for automotive applications

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