Mesoscopic model for colloidal particles, powders and granular solids

A simulation model is presented, comprising elastic spheres with a short range attraction. Besides conservative forces, radial- and shear friction, and radial noise are added. The model can be used to simulate colloids, granular solids and powders, and the parameters may be related to experimental systems via the range of attraction and the adhesion energy. The model shares the simplicity and speed of Dissipative Particle Dynamics (DPD), yet the predictions are rather non-trivial. We demonstrate that the model predicts the correct scaling relations for fracture of granular solids, and we present a schematic phase diagram. This shows liquid-vapor coexistence for sufficiently large interaction range, with a surface tension that follows Ising criticality. For smaller interaction range only solid-vapor coexistence is found, but for very small attractive interaction range stable liquid-vapor coexistence reappears due to pathological stability of the solid phase. At very low temperature the model forms a glassy state.Comment: 12 pages, 6 figures, accepted by Physical Review E, typos correcte

Vehicle and crew scheduling: solving large real-world instances with an integrated approach

In this paper we discuss several methods to solve large real-worldinstances of the vehicle and crew scheduling problem. Although,there has been an increased attention to integrated approaches forsolving such problems in the literature, currently only small ormedium-sized instances can be solved by such approaches.Therefore, large instances should be split into several smallerones, which can be solved by an integrated approach, or thesequential approach, i.e. first vehicle scheduling and afterwardscrew scheduling, is applied.In this paper we compare both approaches, where we considerdifferent ways of splitting an instance varying from very simplerules to more sophisticated ones. Those ways are extensivelytested by computational experiments on real-world data provided bythe largest Dutch bus company.

Mapping of sensitivity to oil spills in the Lithuanian Baltic Sea coast.

This research develops an integrated environmental assessment tool for Lithuanian coastal area that takes due account of the major oil spill risks posed by the D-6 oil drilling platform, vessel traffic in the south-eastern Baltic Sea, and operation of the Butinge oil terminal. The goal of this paper is to present an environmental sensitivity index (ESI) mapping approach based on four specific indexes: coastal features (ESIC), socio-economic aspects (ESISE), biological (ESIB) and fishery resources (ESIF). The relevant methodology approach was selected. The core dataset is provided by GIS-based environmental atlas updated with other relevant GIS data of Lithuanian coastal resources. Four ESI maps were developed and an overall environmental sensitivity index (OESI) map produced. Results indicate that in the case of an oil spill, two areas need to be prioritized due to their biologic and socio-economic resources: the 25 km long shoreline between the settlements of Nida-Juodkrante on the Curonian Spit (CS) and the mainland coast (MC) between the settlements Palanga and Sventoji

Openings of the rat recombinant alpha1 homomeric glycine receptor as a function of the number of sgonist molecules bound

The functional properties of rat homomeric {alpha}1 glycine receptors were investigated using whole-cell and outside-out recording from human embryonic kidney cells transfected with rat {alpha}1 subunit cDNA. Whole-cell dose-response curves gave EC50 estimates between 30 and 120 µM and a Hill slope of ~3.3. Single channel recordings were obtained by steady-state application of glycine (0.3, 1, or 10 µM) to outside-out patches. Single channel conductances were mostly 60–90 pS, but smaller conductances of ~40 pS were also seen (10% of the events) with a relative frequency that did not depend on agonist concentration. The time constants of the apparent open time distributions did not vary with agonist concentration, but short events were more frequent at low glycine concentrations. There was also evidence of a previously missed short-lived open state that was more common at lower glycine concentrations. The time constants for the different components of the burst length distributions were found to have similar values at different concentrations. Nevertheless, the mean burst length increased with increasing glycine. This was because the relative area of each burst-length component was concentration dependent and short bursts were favored at lower glycine concentrations. Durations of adjacent open and shut times were found to be strongly (negatively) correlated. Additionally, long bursts were made up of longer than average openings separated by short gaps, whereas short bursts usually consisted of single isolated short openings. The most plausible explanation for these findings is that long bursts are generated when a higher proportion of the five potential agonist binding sites on the receptor is occupied by glycine. On the basis of the concentration dependence and the intraburst structure we provide a preliminary kinetic scheme for the activation of the homomeric glycine receptor, in which any number of glycine molecules from one to five can open the channel, although not with equal efficiency

The activation mechanism of alpha 1 homomeric glycine receptors

The glycine receptor mediates fast synaptic inhibition in the spinal cord and brainstem. Its activation mechanism is not known, despite the physiological importance of this receptor and the fact that it can serve as a prototype for other homopentameric channels. We analyzed single-channel recordings from rat recombinant alpha1 glycine receptors by fitting different mechanisms simultaneously to sets of sequences of openings at four glycine concentrations (10-1000 muM). The adequacy of the mechanism and the rate constants thus fitted was judged by examining how well these described the observed dwell-time distributions, open-shut correlation, and single-channel P-open dose-response curve. We found that gating efficacy increased as more glycine molecules bind to the channel, but maximum efficacy was reached when only three (of five) potential binding sites are occupied. Successive binding steps are not identical, implying that binding sites can interact while the channel is shut. These interactions can be interpreted in the light of the topology of the binding sites within a homopentamer

Single channel study of the spasmodic mutation α1A52S in recombinant rat glycine receptors

Inherited defects in glycine receptors lead to hyperekplexia, or startle disease. A mutant mouse, spasmodic, that has a startle phenotype, has a point mutation (A52S) in the glycine receptor α1 subunit. This mutation reduces the sensitivity of the receptor to glycine, but the mechanism by which this occurs is not known. We investigated the properties of A52S recombinant receptors by cell-attached patch clamp recording of single-channel currents elicited by 30 – 10000 μM glycine. We used heteromeric receptors, which resemble those found at adult inhibitory synapses. Activation mechanisms were fitted directly to single channel data using the HJCFIT method, which includes an exact correction for missed events. In common with wildtype receptors, only mechanisms with three binding sites and extra shut states could describe the observations. The most physically plausible of these, the ‘flip’ mechanism, suggests that pre-opening isomerisation to the flipped conformation that follows binding is less favoured in mutant than in wild-type receptors, and, especially, that the flipped conformation has a 100-fold lower affinity for glycine than in wildtype receptors. In contrast, the efficacy of the gating reaction was similar to that of wild-type heteromeric receptors. The reduction in affinity for the flipped conformation accounts for the reduction in apparent cooperativity seen in the mutant receptor (without having to postulate interaction between the binding sites) and it accounts for the increased EC50 for responses to glycine that is seen in mutant receptors. This mechanism also predicts accurately the faster decay of synaptic currents that is observed in spasmodic mice