A General Vehicle Routing Problem

In this paper, we study a rich vehicle routing problem incorporating various complexities found in real-life applications. The General Vehicle Routing Problem (GVRP) is a combined load acceptance and generalised vehicle routing problem. Among the real-life requirements are time window restrictions, a heterogeneous vehicle fleet with different travel times, travel costs and capacity, multi-dimensional capacity constraints, order/vehicle compatibility constraints, orders with multiple pickup, delivery and service locations, different start and end locations for vehicles, and route restrictions for vehicles. The GVRP is highly constrained and the search space is likely to contain many solutions such that it is impossible to go from one solution to another using a single neighbourhood structure. Therefore, we propose iterative improvement approaches based on the idea of changing the neighbourhood structure during the search.     

Rapid and accurate estimation of protein–ligand relative binding affinities using site-identification by ligand competitive saturation

Predicting relative protein–ligand binding affinities is a central pillar of lead optimization efforts in structure-based drug design. The site identification by ligand competitive saturation (SILCS) methodology is based on functional group affinity patterns in the form of free energy maps that may be used to compute protein–ligand binding poses and affinities. Presented are results obtained from the SILCS methodology for a set of eight target proteins as reported originally in Wang et al. (J. Am. Chem. Soc., 2015, 137, 2695–2703) using free energy perturbation (FEP) methods in conjunction with enhanced sampling and cycle closure corrections. These eight targets have been subsequently studied by many other authors to compare the efficacy of their method while comparing with the outcomes of Wang et al. In this work, we present results for a total of 407 ligands on the eight targets and include specific analysis on the subset of 199 ligands considered previously. Using the SILCS methodology we can achieve an average accuracy of up to 77% and 74% when considering the eight targets with their 199 and 407 ligands, respectively, for rank-ordering ligand affinities as calculated by the percent correct metric. This accuracy increases to 82% and 80%, respectively, when the SILCS atomic free energy contributions are optimized using a Bayesian Markov-chain Monte Carlo approach. We also report other metrics including Pearson''s correlation coefficient, Pearlman''s predictive index, mean unsigned error, and root mean square error for both sets of ligands. The results obtained for the 199 ligands are compared with the outcomes of Wang et al. and other published works. Overall, the SILCS methodology yields similar or better-quality predictions without a priori need for known ligand orientations in terms of the different metrics when compared to current FEP approaches with significant computational savings while additionally offering quantitative estimates of individual atomic contributions to binding free energies. These results further validate the SILCS methodology as an accurate, computationally efficient tool to support lead optimization and drug discovery.

Predicting relative protein–ligand binding affinities is a central pillar of lead optimization efforts in structure-based drug design.     

Enhancing the dissolution of hydrophobic guests using solid state inclusion complexation: characterization and in vitro evaluation

The objectives of the present investigation were to prepare and characterize solid inclusion complexes of Etodolac (ETD) with β-cyclodextrin (β-CD) in order to study the effect of complexation on the dissolution rate of ETD, a hydrophobic guest molecule. Phase solubility curve was classified as a typical A_L-type for the cyclodextrins (CD’s), showing that soluble complex was formed. The inclusion complexes in the molar ratio of 1:1 and 1:2 (β-CD–ETD) were prepared by various methods such as kneading, co-evaporation and in molar ratio of 1:1 by spray dried technique respectively. The molecular behaviors of ETD in all samples were characterized by nuclear magnetic resonance (NMR) spectroscopy, fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies and Scanning Electron microscopy (SEM) analysis. The results of these studies indicated that complexes prepared by kneading, co-evaporation and spray drying techniques showed inclusion of the ETD molecule into the CD’s cavities. The highest improvement in in vitro dissolution profiles was observed in complexes prepared with spray dried technique. Mean in vitro dissolution time indicated significant difference between the release profiles of ETD from complexes and physical mixtures and from pure ETD.     

Effect of sphere to rod transition on the probe microenvironment in sodium dodecyl sulphate micelles: A time resolved fluorescence anisotropy study

The effect of different hydrotropic salts on the microenvironment at the anionic head group region of sodium dodecyl sulphate (SDS) micelle has been studied through time-resolved fluorescence anisotropy measurements of a solubilized probe, coumarin-153 (C153). The organic cations of the hydrotropic salts used in this study, i.e. aniline hydrochloride (AHC) and o-, m- and p-toluidine hydrochlorides (OTHC, MTHC and PTHC, respectively), differ in their charge to size ratio and hydrophobicity. Present study utilizes the sensitivity of the fluorescence technique to understand the changes in the micropolarity and microviscosity experienced by the fluorescent probe, C153, solubilized in the micellar Stern layer, on addition of different hydrotropic salts. Significant changes are observed in the rotational relaxation dynamics of the probe with increasing concentration of the salts. The changes in the rotational relaxation dynamics clearly reflect the sphere to rod transition in the SDS micelles and correspond nicely with the reported results from dynamic light scattering measurements. The growth behavior of SDS micelles is found to be sensitive to the hydrophobicity of the organic cations. The charge to size ratio of the organic cations also indicated to play a role in inducing the sphere to rod transition in the SDS micelles. The interesting observation made from this study is that the sphere to rod transition of SDS micelles is largely facilitated by the presence of the hydrotropic salts and such a transition is successfully indicated by the simple fluorescence anisotropy measurements of a probe in the micelle carried out in the presence of different hydrotropic salts.     

Structural characterisation and thermo-physical properties of glasses in the Li<Subscript>2</Subscript>O–SiO<Subscript>2</Subscript>–Al<Subscript>2</Subscript>O<Subscript>3</Subscript>–K<Subscript>2</Subscript>O system

This article aims to shed some light on the structure and thermo-physical properties of lithium disilicate glasses in the system Li₂O–SiO₂–Al₂O₃–K₂O. A glass with nominal composition 23Li₂O–77SiO₂ (mol%) (labelled as L₂₃S₇₇) and glasses containing Al₂O₃ and K₂O with SiO₂/Li₂O molar ratios (3.13–4.88) were produced by conventional melt-quenching technique in bulk and frit forms. The glass-ceramics (GCs) were obtained from nucleation and crystallisation of monolithic bulk glasses as well as via sintering and crystallisation of glass powder compacts. The structure of glasses as investigated by magic angle spinning-nuclear magnetic resonance (MAS-NMR) depict the role of Al₂O₃ as glass network former with four-fold coordination, i.e., Al(IV) species while silicon exists predominantly as a mixture of Q ³ and Q ⁴ (Si) structural units. The qualitative as well as quantitative crystalline phase evolution in glasses was followed by differential thermal analysis (DTA), X-ray diffraction (XRD) adjoined with Rietveld-reference intensity ratio (R.I.R.) method, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The possible correlation amongst structural features of glasses, phase composition and thermo-physical properties of GCs has been discussed.     

Mesoscopic spin-dependent reflection experiments on InSb- and InAs-based heterostructures

Spin–orbit interaction in two-dimensional electron systems can lead to a spin-dependent reflection of carriers off a lithographic barrier. Scattering of a spin-unpolarized beam from the barrier leads to the creation of two fully spin-polarized side beams in addition to an unpolarized specularly reflected beam. We experimentally demonstrate a method to create spin-polarized beams of ballistic electrons in mesoscopic samples fabricated on InSb/InAlSb and InAs/AlGaSb heterostructures. We describe two geometries, one open and one closed, in which the spin-dependent reflection and spin-dependent semiclassical trajectories were observed.     

Measurement of the transverse kinetic energies of argon recoil ions produced in 120 MeV -Ar collisions

Measurements were carried out to deduce the transverse kinetic energies of highly charged argon recoil ions produced in single collisions of 120 MeV ions with argon atoms in which the post collision charge states of the projectiles were not determined. A time of flight spectrometer was designed and fabricated to detect the charge states of recoils. Experimental procedures for optimizing the spectrometer for extraction, transmission and detection of recoils are described. A simple approach for determining the transverse kinetic energy of the recoil ions from FWHM of the peaks is reported. This method is shown to be independent of the choice of collision partners and requires only the knowledge of the physical values of “optimized parameters” of time-of-flight spectrometer used in the experiment. The transverse kinetic energy of the recoil ions determined from the present approach is found to vary from 0.03 eV for to 4.02 eV for Ar¹⁰⁺. These values are compared with the results reported by earlier workers and are shown to follow a q²-behaviour up to a charge state q =8+ of the recoil ions. Received: 5 February 1998 / Revised: 8 June 1998 / Accepted: 11 June 1998     

Radiation grafting of acrylonitrile on ethylene-propylene diene terpolymer rubber: Optimization of grafting parameters and oil resistance properties

Radiation induced grafting of acrylonitrile (ACN) on ethylene-propene diene terpolymer (EPDM) rubber film was investigated by mutual radiation grafting technique. Effect of experimental variables viz. radiation dose, dose rate, type of solvent and monomer content on extent of grafting was studied. From the kinetic studies a mathematical relation R _g α[M]^0.7 D ^0.68 showing non-linear relationship for rate of grafting with monomer concentration and dose was deduced. The grafted samples showed increased hardness and oil resistance.     

Electroproduction of π+ mesons in the resonance region

Results on the reaction ep→e′nπ⁺ are presented in the mass range 1.355 ?W ?1.775 GeV at q₂=1GeV² and in the range 1.415 ? W ? 1.595 GeV at q²=0.6 GeV². From the angular distribution of the π⁺ meson the polarization terms σ_u + ?σ_L, σ_p and σ_I have been determined in the range of production angles 0 <θ_π⁺ ?63°