Interaction of nitrogen dioxide (NO2) with a monolayer of oleic acid at the air–water interface – A simple proxy for atmospheric aerosol

The reactions between atmospheric oxidants and organic amphiphiles at the air water interface of an aerosol droplet may affect the size and critical supersaturation required for cloud droplet formation. We demonstrate that no reaction occurs between gaseous nitrogen dioxide (1000 ppm in air) and a monolayer of an insoluble amphiphile, oleic acid (cis-9-octadecenoic acid), at the air water interface which removes material from the air water interface. We present evidence that the NO2 isomerises the cis-9-octadecenoic (oleic) acid to trans-9-octadecenoic (elaidic) acid. The study presented here is important for future and previous studies of (1) the reaction between the nitrate radical, NO3, and thin organic films as NO2 is usually present in high concentrations in these experimental systems and (2) the effect of NO2 air pollution on the unsaturated fatty acids and lipids found at the air liquid surface of human lung lining fluid.

Periodic time series modeling of environmental proxy records with guaranteed positive growth rate estimation

Identifying a periodic time-series model from environmental records, without imposing the positivity of the growth rate, does not necessarily respect the time order of the data observations. Consequently, subsequent observations, sampled in the environmental archive, can be inversed on the time axis, resulting in a non-physical signal model. In this paper an optimization technique with linear constraints on the signal model parameters is proposed that prevents time inversions. The activation conditions for this constrained optimization are based upon the physical constraint of the growth rate, namely, that it cannot take values smaller than zero. The actual constraints are defined for polynomials and first-order splines as basis functions for the nonlinear contribution in the distance-time relationship. The method is compared with an existing method that eliminates the time inversions, and its noise sensitivity is tested by means of Monte Carlo simulations. Finally, the usefulness of the method is demonstrated on the measurements of the vessel density, in a mangrove tree, Rhizophora mucronata, and the measurement of Mg/Ca ratios, in a bivalve, Mytilus trossulus.

Health-related quality of life in Huntington’s Disease patients: a comparison of proxy assessment and patient self-rating using the disease-specific Huntington’s Disease health-related quality of life questionnaire (HDQoL)

Huntington’s disease (HD) is a fatal, neurodegenerative disease for which there is no known cure. Proxy evaluation is relevant for HD as its manifestation might limit the ability of persons to report their health-related quality of life (HrQoL). This study explored patient–proxy ratings of HrQoL of persons at different stages of HD, and examined factors that may affect proxy ratings. A total of 105 patient–proxy pairs completed the Huntington’s disease health-related quality of life questionnaire (HDQoL) and other established HrQoL measures (EQ-5D and SF-12v2). Proxy–patient agreement was assessed in terms of absolute level (mean ratings) and intraclass correlation. Proxies’ ratings were at a similar level to patients’ self-ratings on an overall Summary Score and on most of the six Specific Scales of the HDQoL. On the Specific Hopes and Worries Scale, proxies on average rated HrQoL as better than patients’ self-ratings, while on both the Specific Cognitive Scale and Specific Physical and Functional Scale proxies tended to rate HrQoL more poorly than patients themselves. The patient’s disease stage and mental wellbeing (SF-12 Mental Component scale) were the two factors that primarily affected proxy assessment. Proxy scores were strongly correlated with patients’ self-ratings of HrQoL, on the Summary Scale and all Specific Scales. The patient–proxy correlation was lower for patients at moderate stages of HD compared to patients at early and advanced stages. The proxy report version of the HDQoL is a useful complementary tool to self-assessment, and a promising alternative when individual patients with advanced HD are unable to self-report.

The DISOPRED server for the prediction of protein disorder

Dynamically disordered regions appear to be relatively abundant in eukaryotic proteomes. The DISOPRED server allows users to submit a protein sequence, and returns a probability estimate of each residue in the sequence being disordered. The results are sent in both plain text and graphical formats, and the server can also supply predictions of secondary structure to provide further structural information.

The PSIPRED protein structure prediction server

The PSIPRED protein structure prediction server allows users to submit a protein sequence, perform a prediction of their choice and receive the results of the prediction both textually via e-mail and graphically via the web. The user may select one of three prediction methods to apply to their sequence: PSIPRED, a highly accurate secondary structure prediction method; MEMSAT 2, a new version of a widely used transmembrane topology prediction method; or GenTHREADER, a sequence profile based fold recognition method.

The ModFOLD4 server for the quality assessment of 3D protein models

Once you have generated a 3D model of a protein, how do you know whether it bears any resemblance to the actual structure? To determine the usefulness of 3D models of proteins, they must be assessed in terms of their quality by methods that predict their similarity to the native structure. The ModFOLD4 server is the latest version of our leading independent server for the estimation of both the global and local (per-residue) quality of 3D protein models. The server produces both machine readable and graphical output, providing users with intuitive visual reports on the quality of predicted protein tertiary structures. The ModFOLD4 server is freely available to all at: http://www.reading.ac.uk/bioinf/ModFOLD/.

The FunFOLD2 server for the prediction of protein-ligand interactions

The FunFOLD2 server is a new independent server that integrates our novel protein–ligand binding site and quality assessment protocols for the prediction of protein function (FN) from sequence via structure. Our guiding principles were, first, to provide a simple unified resource to make our function prediction software easily accessible to all via a simple web interface and, second, to produce integrated output for predictions that can be easily interpreted. The server provides a clean web interface so that results can be viewed on a single page and interpreted by non-experts at a glance. The output for the prediction is an image of the top predicted tertiary structure annotated to indicate putative ligand-binding site residues. The results page also includes a list of the most likely binding site residues and the types of predicted ligands and their frequencies in similar structures. The protein–ligand interactions can also be interactively visualized in 3D using the Jmol plug-in. The raw machine readable data are provided for developers, which comply with the Critical Assessment of Techniques for Protein Structure Prediction data standards for FN predictions. The FunFOLD2 webserver is freely available to all at the following web site: http://www.reading.ac.uk/bioinf/FunFOLD/FunFOLD_form_2_0.html.

Assessing the quality of modelled 3D protein structures using the ModFOLD server

Model quality assessment programs (MQAPs) aim to assess the quality of modelled 3D protein structures. The provision of quality scores, describing both global and local (per-residue) accuracy are extremely important, as without quality scores we are unable to determine the usefulness of a 3D model for further computational and experimental wet lab studies.Here, we briefly discuss protein tertiary structure prediction, along with the biennial Critical Assessment of Techniques for Protein Structure Prediction (CASP) competition and their key role in driving the field of protein model quality assessment methods (MQAPs). We also briefly discuss the top MQAPs from the previous CASP competitions. Additionally, we describe our downloadable and webserver-based model quality assessment methods: ModFOLD3, ModFOLDclust, ModFOLDclustQ, ModFOLDclust2, and IntFOLD-QA. We provide a practical step-by-step guide on using our downloadable and webserver-based tools and include examples of their application for improving tertiary structure prediction, ligand binding site residue prediction, and oligomer predictions.

Landscape change in central Latvia since the Iron Age: multi-proxy analysis of the vegetation impact of conflict, colonization and economic expansion during the last 2000 years

This study represents the first detailed multi-proxy palaeoenvironmental investigation associated with a Late Iron Age lake-dwelling site in the eastern Baltic. The main objective was to reconstruct the environmental and vegetation dynamics associated with the establishment of the lake-dwelling and land-use during the last 2,000 years. A lacustrine sediment core located adjacent to a Late Iron Age lake-dwelling, medieval castle and Post-medieval manor was sampled in Lake Āraiši. The core was dated using spheroidal fly-ash particles and radiocarbon dating, and analysed in terms of pollen, non-pollen palynomorphs, diatoms, loss-on-ignition, magnetic susceptibility and element geochemistry. Associations between pollen and other proxies were statistically tested. During ad 1–700, the vicinity of Lake Āraiši was covered by forests and human activities were only small-scale with the first appearance of cereal pollen (Triticum and Secale cereale) after ad 400. The most significant changes in vegetation and environment occurred with the establishment of the lake-dwelling around ad 780 when the immediate surroundings of the lake were cleared for agriculture, and within the lake there were increased nutrient levels. The highest accumulation rates of coprophilous fungi coincide with the occupation of the lake-dwelling from ad 780–1050, indicating that parts of the dwelling functioned as byres for livestock. The conquest of tribal lands during the crusades resulted in changes to the ownership, administration and organisation of the land, but our results indicate that the form and type of agriculture and land-use continued much as it had during the preceding Late Iron Age.

IntFOLD: an integrated server for modelling protein structures and functions from amino acid sequences

IntFOLD is an independent web server that integrates our leading methods for structure and function prediction. The server provides a simple unified interface that aims to make complex protein modelling data more accessible to life scientists. The server web interface is designed to be intuitive and integrates a complex set of quantitative data, so that 3D modelling results can be viewed on a single page and interpreted by non-expert modellers at a glance. The only required input to the server is an amino acid sequence for the target protein. Here we describe major performance and user interface updates to the server, which comprises an integrated pipeline of methods for: tertiary structure prediction, global and local 3D model quality assessment, disorder prediction, structural domain prediction, function prediction and modelling of protein-ligand interactions. The server has been independently validated during numerous CASP (Critical Assessment of Techniques for Protein Structure Prediction) experiments, as well as being continuously evaluated by the CAMEO (Continuous Automated Model Evaluation) project. The IntFOLD server is available at: http://www.reading.ac.uk/bioinf/IntFOLD/