CoMFA and homology-based models of the glycine binding site of N-methyl-D-aspartate receptor

Homology modeling was used to build 3D models of the N-methyl-D-aspartate (NMDA) receptor glycine binding site on the basis of an X-ray structure of the water-soluble AMPA-sensitive receptor. The docking of agonists and antagonists to these models was used to reveal binding modes of ligands and to explain known structure-activity relationships. Two types of quantitative models, 3D-QSAR/CoMFA and a regression model based on docking energies, were built for antagonists (derivatives of 4-hydroxy-2-quinolone, quinoxaline-2,3-dione, and related compounds). The CoMFA steric and electrostatic maps were superimposed on the homology-based model, and a close correspondence was marked. The derived computational models have permitted the evaluation of the structural features crucial for high glycine binding site affinity and are important for the design of new ligands.

Constructing networks of continuous-time velocity-based models

A conventional local model (LM) network consists of a set of affine local models blended together using appropriate weighting functions. Such networks have poor interpretability since the dynamics of the blended network are only weakly related to the underlying local models. In contrast, velocity-based LM networks employ strictly linear local models to provide a transparent framework for nonlinear modelling in which the global dynamics are a simple linear combination of the local model dynamics. A novel approach for constructing continuous-time velocity-based networks from plant data is presented. Key issues including continuous-time parameter estimation, correct realisation of the velocity-based local models and avoidance of the input derivative are all addressed. Application results are reported for the highly nonlinear simulated continuous stirred tank reactor process.

On the nudging terms at open boundaries in regional ocean models

For open boundary conditions (OBCs) in regional models, a nudging term added to radiative and/or advective conditions during the wave or flow propagation outward from the model domain of interest is widely used, to prevent the predicted boundary values from evolving to become quite different from the external data, especially for a long-term integration. However, nudging time scales are basically unknown, leading to many empirical selections. In this paper, a method for objectively estimating nudging time scales during outward propagation is proposed, by using internal model dynamics near the boundary. We tested this method and other several commonly used OBCs for cases of both an idealized model domain and a realistic configuration, and model results demonstrated that the proposed method improves the model solutions. Many similarities are found between the nudging and mixing time scales, in magnitude, spatial and temporal variations, since the nudging mainly replaces the effect of the mixing terms in this study. However, the mixing time scale is not an intrinsic property of the nudging term because in other studies the nudging term might replace terms other than the mixing terms and, thus, should reflect other characteristic time scales.

High temperature thermal stability investigations of ammonium sulphide passivated InGaAs and interface formation with Al2O3 studied by synchrotron radiation based photoemission

High resolution synchrotron radiation core level photoemission measurements have been used to undertake a comparative study ofthe high temperature thermal stability ofthe ammonium sulphide passivated InGaAs surface and the same surface following the atomic layer deposition (ALD) of an ultrathin (∼1 nm) Al2O3 layer. The solution based ex situ sulphur passivation was found to be effective at removing a significant amount of the native oxides and protecting the surface against re-oxidation upon air exposure. The residual interfacial oxides which form between sulphur passivated InGaAs and the ultrathin Al2O3 layer can be substantially removed at high temperature (up to 700 ◦C) without impacting on the InGaAs stoichiometry while significant loss of indium was recorded at this temperature on the uncovered sulphur passivated InGaAs surface.

High-temperature stability study of 1 nm Al2O3 deposited on InAs surfaces investigated by synchrotron radiation based photoemission spectroscopy

High-resolution soft x-ray photoemission spectroscopy (SXPS) has been used to study the high-temperature thermal stability of ultra-thin atomic layer deposited (ALD) Al2O3 layers (~1 nm) on sulfur passivated and native oxide covered InAs surfaces. While the arsenic oxides were removed from both interfaces following a 600 °C anneal, a residual indium oxide signal remained. No significant differences were observed between the sulfur passivated and native oxide surfaces other than the thickness of the interfacial oxide layer while the Al2O3 stoichiometry remained unaffected by the anneals. The energy band offsets were determined for the Al2O3 on the sulfur passivated InAs surface using both valence band edge and shallow core-level photoemission measurements.

Chloride ingress into marine exposed concrete: A comparison of empirical- and physically- based models

In establishing the reliability of performance-related design methods for concrete – which are relevant for resistance against chloride-induced corrosion - long-term experience of local materials and practices and detailed knowledge of the ambient and local micro-climate are critical. Furthermore, in the development of analytical models for performance-based design, calibration against test data representative of actual conditions in practice is required. To this end, the current study presents results from full-scale, concrete pier-stems under long-term exposure to a marine environment with work focussing on XS2 (below mid-tide level) in which the concrete is regarded as fully saturated and XS3 (tidal, splash and spray) in which the concrete is in an unsaturated condition. These exposures represent zones where concrete structures are most susceptible to ionic ingress and deterioration. Chloride profiles and chloride transport behaviour are studied using both an empirical model (erfc function) and a physical model (ClinConc). The time dependency of surface chloride concentration (Cs) and apparent diffusivity (Da) were established for the empirical model whereas, in the ClinConc model (originally based on saturated concrete), two new environmental factors were introduced for the XS3 environmental exposure zone. Although the XS3 is considered as one environmental exposure zone according to BS EN 206-1:2013, the work has highlighted that even within this zone, significant changes in chloride ingress are evident. This study aims to update the parameters of both models for predicting the long term transport behaviour of concrete subjected to environmental exposure classes XS2 and XS3.

Models of open populations with space-limited recruitment: extension of theory and application to the barnacle Chthamalus montagui.

1. Barnacles are a good model organism for the study of open populations with space-limited recruitment. These models are applicable to other species with open supply of new individuals and resource limitation. The inclusion of space in models leads to reductions in recruitment with increasing density, and thus predictions of population size and stability are possible. 2. Despite the potential generality of a demographic theory for open space-limited populations, the models currently have a narrow empirical base. In this study, a model for an open population with space-limited recruitment was extended to include size-specific survival and promotions to any size class. The assumptions of this model were tested using data from a pan-European study of the barnacle Chthamalus montagui Southward. Two models were constructed: a 6-month model and a periodic annual model. Predicted equilibria and their stabilities were compared between shores. 3. Tests of model assumptions supported the extension of the theory to include promotions to any size class. Mortality was found to be size-specific and density independent. Studied populations were open, with recruitment proportional to free space. 4. The 6-month model showed a significant interaction between time and location for equilibrium free space. This may have been due to contrasts in the timing of structuring processes (i.e. creating and filling space) between Mediterranean and Atlantic systems. Integration of the 6-month models into a periodic annual model removed the differences in equilibrium-free space between locations. 5. Model predictions show a remarkable similarity between shores at a European scale. Populations were persistent and all solutions were stable. This reflects the apparent absence of density-dependent mortality and a high adult survivorship in C. montagui. As populations are intrinsically stable, observations of fluctuations in density are directly attributable to variations in the environmental forcing of recruitment or mortality

Structural basis for understanding structure-activity relationships for the glutamate binding site of the NMDA receptor

We present new homology-based models of the glutamate binding site (in closed and open forms) of the NMDA receptor NR2B subunit derived from X-ray structures of the water soluble AMPA sensitive glutamate receptor. The models were used for revealing binding modes of agonists and competitive antagonists, as well as for rationalizing known experimental facts concerning structure-activity relationships: (i) the switching between the agonist and the antagonist modes of action upon lengthening the chain between the distal acidic group and the amino acid moiety, (ii) the preference for the methyl group attached to the a-amino group of ligands, (iii) the preference for the D-configuration of agonists and antagonists, and (iv) the existence of "superacidic" agonists.

Adoption of farm-based irrigation water-saving techniques in the Guanzhong Plain, China

This article analyses adoption of farm-based irrigation water saving techniques, based on a cross-sectional data set of 357 farmers in the Guanzhong Plain, China. Approximately 83% of the farmers use at least one farm-based water-saving technique. However, the traditional, inefficient techniques border and furrow irrigation are still prevalent whereas the use of advanced, more efficient techniques is still rather rare. We develop and estimate an adoption model consisting of two stages: awareness of water scarcity and intensity of adoption. We find that awareness of water scarcity and financial status enhance adoption of more advanced techniques whereas access to better community-based irrigation infrastructure discourages it. We furthermore find both community-based irrigation infrastructure and farm-based irrigation water-saving techniques have mitigating effects on production risk. From the results it follows that adoption can be stimulated via financial support and via extension aimed at enhancing awareness of water scarcity.

Temporal variation in the water chemistry of northern Victoria Land lakes (Antarctica)

Concentrations of major ions, silicate and nutrients (total N and P) were measured in samples of surface water from 28 lakes in ice-free areas of northern Victoria Land (East Antarctica). Sixteen lakes were sampled during austral summers 2001/02, 2003/04, 2004/05 and 2005/06 to assess temporal variation in water chemistry. Although samples showed a wide range in ion concentrations, their composition mainly reflected that of seawater. In general, as the distance from the sea increased, the input of elements from the marine environment (through aerosols and seabirds) decreased and there was an increase in nitrate and sulfate concentrations. Antarctic lakes lack outflows and during the austral summer the melting and/or ablation of ice cover, water evaporation and leaching processes in dry soils determine a progressive increase in water ion concentrations. During the five-year monitoring survey, no statistically significant variation in the water chemistry were detected, except for a slight (hardly significant) increase in TN concentrations. However, Canonical Correspondence Analysis (CCA) indicated that other factors besides distance from the sea, the presence of nesting seabirds, the sampling time and percentage of ice cover affect the composition of water in Antarctic cold desert environments.

The impacts of management reform on irrigation water use efficiency in the Guanzhong plain, China

This paper examines the efficiency of the 1998 irrigation management reform in the Guanzhong Plain, Shaanxi, China, at farm and canal level. Stochastic frontier analysis is applied to estimate irrigation water use efficiency, based on panel data for 800 farmers, spread over 80 irrigation canals, for the period 1999–2005. Analysis of determinants of water use efficiency shows that at farm level, water price and disclosure are important factors. Compared to the base case of unreformed, management reform has a positive impact with water user association having the largest effect, followed by joint-stock co-operative and private company. The canal model is in line with the farm level model, although estimates are less significant.

Simulating reinforced concrete members. Part 2: displacement-based analyses

A companion paper described the partial-interaction localised properties that require the development of pseudo properties. If the quantification through experimental testing of these pseudo properties could be removed by the use of mechanics-based models, which is the subject of this paper, then this would: (a) substantially reduce the cost of developing new reinforced concrete products by reducing the amount of testing; (b) increase the accuracy of designing existing and novel reinforced concrete members and structures, bearing in mind that experimentally derived pseudo properties are only applicable within the range of the testing from which they were derived; and (c) reduce the cost and increase the accuracy of developing reinforced concrete design rules. This paper deals with the development of pseudo properties and behaviours directly through mechanics, as opposed to experimental testing, and their incorporation into member global simulations. It also addresses the need for a fundamental shift to displacement-based analyses as opposed to strain-based analyses.