Differential recognition of Staphylococcus aureus quorum-sensing signals depends on both extracellular loops 1 and 2 of the transmembrane sensor AgrC.

Virulence in Staphylococcus aureus is regulated via agr-dependent quorum sensing in which an autoinducing peptide (AIP) activates AgrC, a histidine protein kinase. AIPs are usually thiolactones containing seven to nine amino acid residues in which the thiol of the central cysteine is linked to the alpha-carboxyl of the C-terminal amino acid residue. The staphylococcal agr locus has diverged such that the AIPs of the four different S. aureus agr groups self-activate but cross-inhibit. Consequently, although the agr system is conserved among the staphylococci, it has undergone significant evolutionary divergence whereby to retain functionality, any changes in the AIP-encoding gene (agrD) that modifies AIP structure must be accompanied by corresponding changes in the AgrC receptor. Since AIP-1 and AIP-4 only differ by a single amino acid, we compared the transmembrane topology of AgrC1 and AgrC4 to identify amino acid residues involved in AIP recognition. As only two of the three predicted extracellular loops exhibited amino acid differences, site-specific mutagenesis was used to exchange the key AgrC1 and AgrC4 amino acid residues in each loop either singly or in combination. A novel lux-based agrP3 reporter gene fusion was constructed to evaluate the response of the mutated AgrC receptors. The data obtained revealed that while differential recognition of AIP-1 and AIP-4 depends primarily on three amino acid residues in loop 2, loop 1 is essential for receptor activation by the cognate AIP. Furthermore, a single mutation in the AgrC1 loop 2 resulted in conversion of (Ala5)AIP-1 from a potent antagonist to an activator, essentially resulting in the forced evolution of a new AIP group. Taken together, our data indicate that loop 2 constitutes the predicted hydrophobic pocket that binds the AIP thiolactone ring while the exocyclic amino acid tail interacts with loop 1 to facilitate receptor activation.

Measurement and prediction of the effect of students activities on airborne particulate concentration in a classroom.

Epidemiological studies have shown links between human exposure to indoor airborne particles and adverse health affects. Several recent studies have also reported that the classroom environment has an impact on students’ health and performance. In this study particle concentration in a university classroom is assessed experimentally for different occupancy periods. The mass concentrations of different particle size ranges (0.3 – 20 µm), and the three particulate matter fractions (PM10, PM2.5, and PM1) were measured simultaneously in a classroom with different occupancy periods including occupied and unoccupied periods in the University of Reading, UK, during the winter period of 2010. The results showed that students’ presence is a significant factor affecting particles concentration for the fractions above PM1 in the measured range of 0.3 to 20 µm. The resuspension of the three PM fractions was also determined in the study.

Dual-orthogonal radial basis function networks for nonlinear time series prediction

A new structure of Radial Basis Function (RBF) neural network called the Dual-orthogonal RBF Network (DRBF) is introduced for nonlinear time series prediction. The hidden nodes of a conventional RBF network compare the Euclidean distance between the network input vector and the centres, and the node responses are radially symmetrical. But in time series prediction where the system input vectors are lagged system outputs, which are usually highly correlated, the Euclidean distance measure may not be appropriate. The DRBF network modifies the distance metric by introducing a classification function which is based on the estimation data set. Training the DRBF networks consists of two stages. Learning the classification related basis functions and the important input nodes, followed by selecting the regressors and learning the weights of the hidden nodes. In both cases, a forward Orthogonal Least Squares (OLS) selection procedure is applied, initially to select the important input nodes and then to select the important centres. Simulation results of single-step and multi-step ahead predictions over a test data set are included to demonstrate the effectiveness of the new approach.

Amyloid-like fibrillogenesis through supramolecular helix-mediated self-assembly of tetrapeptides containing non-coded alpha-aminoisobutyric acid (Aib) and 3-aminobenzoic acid (m-ABA)

Single-crystal X-ray diffraction studies of two terminally protected tetrapeptides Boc-Ile-Aib-Val-m-ABA-OMe (I) and Boc-Ile-Aib-Phe-m-ABA-OMe (II) (Aib = alpha-aminoisobutyric acid; m-ABA = meta-aminobenzoic acid) reveal that they form continuous H-bonded helices through the association of double-bend (type III and I) building blocks. NMR Studies support the existence of the double-bend (type Ill and I) structures of the peptides in solution also. Field emission scanning electron-microscopic (FE-SEM) and high-resolution transmission electron-microscopic (HR-TEM) images of the peptides exhibit amyloid-like fibrils in the solid state. The Congo red-stained fibrils of peptide I and II, observed between crossed polarizers, show green-gold birefringence, a characteristic of amyloid fibrils.

On the utility of input selection and pruning for financial distress prediction models

Analyzes the use of linear and neural network models for financial distress classification, with emphasis on the issues of input variable selection and model pruning. A data-driven method for selecting input variables (financial ratios, in this case) is proposed. A case study involving 60 British firms in the period 1997-2000 is used for illustration. It is shown that the use of the Optimal Brain Damage pruning technique can considerably improve the generalization ability of a neural model. Moreover, the set of financial ratios obtained with the proposed selection procedure is shown to be an appropriate alternative to the ratios usually employed by practitioners.

Ensemble prediction for nowcasting with a convection-permitting model—I: description of the system and the impact of radar-derived surface precipitation rates

A key strategy to improve the skill of quantitative predictions of precipitation, as well as hazardous weather such as severe thunderstorms and flash floods is to exploit the use of observations of convective activity (e.g. from radar). In this paper, a convection-permitting ensemble prediction system (EPS) aimed at addressing the problems of forecasting localized weather events with relatively short predictability time scale and based on a 1.5 km grid-length version of the Met Office Unified Model is presented. Particular attention is given to the impact of using predicted observations of radar-derived precipitation intensity in the ensemble transform Kalman filter (ETKF) used within the EPS. Our initial results based on the use of a 24-member ensemble of forecasts for two summer case studies show that the convective-scale EPS produces fairly reliable forecasts of temperature, horizontal winds and relative humidity at 1 h lead time, as evident from the inspection of rank histograms. On the other hand, the rank histograms seem also to show that the EPS generates too much spread for forecasts of (i) surface pressure and (ii) surface precipitation intensity. These may indicate that for (i) the value of surface pressure observation error standard deviation used to generate surface pressure rank histograms is too large and for (ii) may be the result of non-Gaussian precipitation observation errors. However, further investigations are needed to better understand these findings. Finally, the inclusion of predicted observations of precipitation from radar in the 24-member EPS considered in this paper does not seem to improve the 1-h lead time forecast skill.

Ensemble prediction for nowcasting with a convection-permitting model - II: forecast error statistics

A 24-member ensemble of 1-h high-resolution forecasts over the Southern United Kingdom is used to study short-range forecast error statistics. The initial conditions are found from perturbations from an ensemble transform Kalman filter. Forecasts from this system are assumed to lie within the bounds of forecast error of an operational forecast system. Although noisy, this system is capable of producing physically reasonable statistics which are analysed and compared to statistics implied from a variational assimilation system. The variances for temperature errors for instance show structures that reflect convective activity. Some variables, notably potential temperature and specific humidity perturbations, have autocorrelation functions that deviate from 3-D isotropy at the convective-scale (horizontal scales less than 10 km). Other variables, notably the velocity potential for horizontal divergence perturbations, maintain 3-D isotropy at all scales. Geostrophic and hydrostatic balances are studied by examining correlations between terms in the divergence and vertical momentum equations respectively. Both balances are found to decay as the horizontal scale decreases. It is estimated that geostrophic balance becomes less important at scales smaller than 75 km, and hydrostatic balance becomes less important at scales smaller than 35 km, although more work is required to validate these findings. The implications of these results for high-resolution data assimilation are discussed.

Ensemble prediction of transitions of the North Atlantic eddy-driven jet

The consistency of ensemble forecasts from three global medium-range prediction systems with the observed transition behaviour of a three-cluster model of the North Atlantic eddy-driven jet is examined. The three clusters consist of a mid jet cluster taken to represent an undisturbed jet and south and north jet clusters representing southward and northward shifts of the jet. The ensemble forecasts span a period of three extended winters (October–February) from October 2007–February 2010. The mean probabilities of transitions between the clusters calculated from the ensemble forecasts are compared with those calculated from a 23-extended-winter climatology taken from the European Centre for Medium-Range Weather Forecasts 40-Year Re-analysis (ERA40) dataset. No evidence of a drift with increasing lead time of the ensemble forecast transition probabilities towards values inconsistent with the 23-extended-winter climatology is found. The ensemble forecasts of transition probabilities are found to have positive Brier Skill at 15 day lead times. It is found that for the three-extended-winter forecast set, probabilistic forecasts initialized in the north jet cluster are generally less skilful than those initialized in the other clusters. This is consistent with the shorter persistence time-scale of the north jet cluster observed in the ERA40 23-extended-winter climatology. Copyright © 2011 Royal Meteorological Society

Automated tertiary structure prediction with accurate local model quality assessment using the IntFOLD-TS method

The IntFOLD-TS method was developed according to the guiding principle that the model quality assessment would be the most critical stage for our template based modelling pipeline. Thus, the IntFOLD-TS method firstly generates numerous alternative models, using in-house versions of several different sequence-structure alignment methods, which are then ranked in terms of global quality using our top performing quality assessment method – ModFOLDclust2. In addition to the predicted global quality scores, the predictions of local errors are also provided in the resulting coordinate files, using scores that represent the predicted deviation of each residue in the model from the equivalent residue in the native structure. The IntFOLD-TS method was found to generate high quality 3D models for many of the CASP9 targets, whilst also providing highly accurate predictions of their per-residue errors. This important information may help to make the 3D models that are produced by the IntFOLD-TS method more useful for guiding future experimental work

Urban tracer dispersion experiment in London (DAPPLE) 2003: field study and comparison with empirical prediction

The DAPPLE (Dispersion of Air Pollutants and their Penetration into the Local Environment) project seeks to characterise near-field urban atmospheric dispersion using a multidisciplinary approach. In this paper we report on the first tracer dispersion experiment carried out in May 2003. Results of concurrent meteorological measurements are presented. Variations of receptor tracer concentration with time are presented. Meteorological observations suggest that in-street channelling and flow-switching at intersections take place. A comparison between roof top and surface measurements suggest that rapid vertical mixing occurs, and a comparison between a simple dispersion model and maximum concentrations observed are presented

Prediction of the thermal performance of horizontal-coupled ground source heat exchangers

The thermal performance of a horizontal-coupled ground-source heat pump system has been assessed both experimentally and numerically in a UK climate. A numerical simulation of thermal behaviour of the horizontal-coupled heat exchanger for combinations of different ambient air temperatures, wind speeds, refrigerant temperature and soil thermal properties was studied using a validated 2D transient model. The specific heat extraction by the heat exchanger increased with ambient temperature and soil thermal conductivity, however it decreased with increasing refrigerant temperature. The effect of wind speed was negligible.

Comparing the UK Met Office climate prediction system DePreSys with idealized predictability in the HadCM3 model

The initial condition effect on climate prediction skill over a 2-year hindcast time-scale has been assessed from ensemble HadCM3 climate model runs using anomaly initialization over the period 1990–2001, and making comparisons with runs without initialization (equivalent to climatological conditions), and to anomaly persistence. It is shown that the assimilation improves the prediction skill in the first year globally, and in a number of limited areas out into the second year. Skill in hindcasting surface air temperature anomalies is most marked over ocean areas, and is coincident with areas of high sea surface temperature and ocean heat content skill. Skill improvement over land areas is much more limited but is still detectable in some cases. We found little difference in the skill of hindcasts using three different sets of ocean initial conditions, and we obtained the best results by combining these to form a grand ensemble hindcast set. Results are also compared with the idealized predictability studies of Collins (Clim. Dynam. 2002; 19: 671–692), which used the same model. The maximum lead time for which initialization gives enhanced skill over runs without initialization varies in different regions but is very similar to lead times found in the idealized studies, therefore strongly supporting the process representation in the model as well as its use for operational predictions. The limited 12-year period of the study, however, means that the regional details of model skill should probably be further assessed under a wider range of observational conditions.

Prediction of coagulation properties, titratable acidity and pH of bovine milk using mid-infrared spectroscopy

This study investigated the potential application of mid-infrared spectroscopy (MIR 4,000–900 cm−1) for the determination of milk coagulation properties (MCP), titratable acidity (TA), and pH in Brown Swiss milk samples (n = 1,064). Because MCP directly influence the efficiency of the cheese-making process, there is strong industrial interest in developing a rapid method for their assessment. Currently, the determination of MCP involves time-consuming laboratory-based measurements, and it is not feasible to carry out these measurements on the large numbers of milk samples associated with milk recording programs. Mid-infrared spectroscopy is an objective and nondestructive technique providing rapid real-time analysis of food compositional and quality parameters. Analysis of milk rennet coagulation time (RCT, min), curd firmness (a30, mm), TA (SH°/50 mL; SH° = Soxhlet-Henkel degree), and pH was carried out, and MIR data were recorded over the spectral range of 4,000 to 900 cm−1. Models were developed by partial least squares regression using untreated and pretreated spectra. The MCP, TA, and pH prediction models were improved by using the combined spectral ranges of 1,600 to 900 cm−1, 3,040 to 1,700 cm−1, and 4,000 to 3,470 cm−1. The root mean square errors of cross-validation for the developed models were 2.36 min (RCT, range 24.9 min), 6.86 mm (a30, range 58 mm), 0.25 SH°/50 mL (TA, range 3.58 SH°/50 mL), and 0.07 (pH, range 1.15). The most successfully predicted attributes were TA, RCT, and pH. The model for the prediction of TA provided approximate prediction (R2 = 0.66), whereas the predictive models developed for RCT and pH could discriminate between high and low values (R2 = 0.59 to 0.62). It was concluded that, although the models require further development to improve their accuracy before their application in industry, MIR spectroscopy has potential application for the assessment of RCT, TA, and pH during routine milk analysis in the dairy industry. The implementation of such models could be a means of improving MCP through phenotypic-based selection programs and to amend milk payment systems to incorporate MCP into their payment criteria.