Kinetic Analysis of Discrete Path Sampling Stationary Point Databases

Analysing stationary point databases to extract phenomenological rate constants can become time-consuming for systems with large potential energy barriers. In the present contribution we analyse several different approaches to this problem. First, we show how the original rate constant prescription within the discrete path sampling approach can be rewritten in terms of committor probabilities. Two alternative formulations are then derived in which the steady-state assumption for intervening minima is removed, providing both a more accurate kinetic analysis, and a measure of whether a two-state description is appropriate. The first approach involves running additional short kinetic Monte Carlo (KMC) trajectories, which are used to calculate waiting times. Here we introduce `leapfrog' moves to second-neighbour minima, which prevent the KMC trajectory oscillating between structures separated by low barriers. In the second approach we successively remove minima from the intervening set, renormalising the branching probabilities and waiting times to preserve the mean first-passage times of interest. Regrouping the local minima appropriately is also shown to speed up the kinetic analysis dramatically at low temperatures. Applications are described where rates are extracted for databases containing tens of thousands of stationary points, with effective barriers that are several hundred times kT.Comment: 28 pages, 1 figure, 4 table

Dynamic Limits on Planar Libration-Orbit Coupling Around an Oblate Primary

This paper explores the dynamic properties of the planar system of an ellipsoidal satellite in an equatorial orbit about an oblate primary. In particular, we investigate the conditions for which the satellite is bound in librational motion or when the satellite will circulate with respect to the primary. We find the existence of stable equilibrium points about which the satellite can librate, and explore both the linearized and non-linear dynamics around these points. Absolute bounds are placed on the phase space of the libration-orbit coupling through the use of zero-velocity curves that exist in the system. These zero-velocity curves are used to derive a sufficient condition for when the satellite's libration is bound to less than 90 degrees. When this condition is not satisfied so that circulation of the satellite is possible, the initial conditions at zero libration angle are determined which lead to circulation of the satellite. Exact analytical conditions for circulation and the maximum libration angle are derived for the case of a small satellite in orbits of any eccentricity.Comment: Submitted to Celestial Mechanics and Dynamical Astronom

Cost-Effective Use of Silver Dressings for the Treatment of Hard-to-Heal Chronic Venous Leg Ulcers

Aim To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs). Background Chronic venous ulceration affects 1–3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial. Methods A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: ‘Healed ulcer’, ‘Healing ulcer’ or ‘No improvement’ were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model. Results Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings. Conclusion The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs

Accounting for thermodynamic non-ideality in the Guinier region of small-angle scattering data of proteins

Hydrodynamic studies of the solution properties of proteins and other biological macromolecules are often hard to interpret when the sample is present at a reasonably concentrated solution. The reason for this is that solutions exhibit deviations from ideal behaviour which is manifested as thermodynamic non-ideality. The range of concentrations at which this behaviour typically is exhibited is as low as 1-2 mg/ml, well within the range of concentrations used for their analysis by techniques such as small-angle scattering. Here we discuss thermodynamic non-ideality used previously used in the context of light scattering and sedimentation equilibrium analytical ultracentrifugation and apply it to the Guinier region of small-angle scattering data. The results show that there is a complementarity between the radially averaged structure factor derived from small-angle X-ray scattering/small-angle neutron scattering studies and the second virial coefficient derived from sedimentation equilibrium analytical ultracentrifugation experiments

Non-homogenous disks in the chain of matrices

We investigate the generating functions of multi-colored discrete disks with non-homogenous boundary conditions in the context of the Hermitian multi-matrix model where the matrices are coupled in an open chain. We show that the study of the spectral curve of the matrix model allows one to solve a set of loop equations to get a recursive formula computing mixed trace correlation functions to leading order in the large matrix limit.Comment: 25 pages, 4 figure

Harnessing optical micro-combs for microwave photonics

In the past decade, optical frequency combs generated by high-Q micro-resonators, or micro-combs, which feature compact device footprints, high energy efficiency, and high-repetition-rates in broad optical bandwidths, have led to a revolution in a wide range of fields including metrology, mode-locked lasers, telecommunications, RF photonics, spectroscopy, sensing, and quantum optics. Among these, an application that has attracted great interest is the use of micro-combs for RF photonics, where they offer enhanced functionalities as well as reduced size and power consumption over other approaches. This article reviews the recent advances in this emerging field. We provide an overview of the main achievements that have been obtained to date, and highlight the strong potential of micro-combs for RF photonics applications. We also discuss some of the open challenges and limitations that need to be met for practical applications.Comment: 32 Pages, 13 Figures, 172 Reference

Ligand-based virtual screening using binary kernel discrimination

This paper discusses the use of a machine-learning technique called binary kernel discrimination (BKD) for virtual screening in drug- and pesticide-discovery programmes. BKD is compared with several other ligand-based tools for virtual screening in databases of 2D structures represented by fragment bit-strings, and is shown to provide an effective, and reasonably efficient, way of prioritising compounds for biological screening

Isolation and characterization of the full-length cDNA encoding a member of a novel cytochrome p450 family (CYP320A1) from the tropical freshwater snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni

Cytochrome p450s (cyp450s) are a family of structurally related proteins, with diverse functions, including steroid synthesis and breakdown of toxins. This paper reports the full-length sequence of a novel cyp450 gene, the first to be isolated from the tropical freshwater snail Biomphalaria glabrata, an important intermediate host of Schistosoma mansoni. The nucleotide sequence is 2291 bp with a predicted amino acid sequence of 584aa. The sequence demonstrates conserved cyp450 structural motifs, but is sufficiently different from previously reported cyp450 sequences to be given a new classification, CYP320A1. Initially identified as down-regulated in partially resistant snails in response to S. mansoni infection, amplification of this gene using RT-PCR in both totally resistant or susceptible snail lines when exposed to infection, and all tissues examined, suggests ubiquitous expression. Characterization of the first cyp450 from B. glabrata is significant in understanding the evolution of these metabolically important proteins