Ocean acoustic models for low frequency propagation in 2D and 3D environments

In this paper we are mainly concerned with the development of efficient computer models capable of accurately predicting the propagation of low-to-middle frequency sound in the sea, in axially symmetric (2D) and in fully 3D environments. The major physical features of the problem, i.e. a variable bottom topography, elastic properties of the subbottom structure, volume attenuation and other range inhomogeneities are efficiently treated. The computer models presented are based on normal mode solutions of the Helmholtz equation on the one hand, and on various types of numerical schemes for parabolic approximations of the Helmholtz equation on the other. A new coupled mode code is introduced to model sound propagation in range-dependent ocean environments with variable bottom topography, where the effects of an elastic bottom, of volume attenuation, surface and bottom roughness are taken into account. New computer models based on finite difference and finite element techniques for the numerical solution of parabolic approximations are also presented. They include an efficient modeling of the bottom influence via impedance boundary conditions, they cover wide angle propagation, elastic bottom effects, variable bottom topography and reverberation effects. All the models are validated on several benchmark problems and versus experimental data. Results thus obtained were compared with analogous results from standard codes in the literature.

Kinematic modeling of head-neck movements

The main objective is to generate kinematic models for the head and neck movements. The motivation comes from our study of individuals with quadriplegia and the need to design rehabilitation aiding devices such as robots and teletheses that can be controlled by head-neck movements. It is then necessary to develop mathematical models for the head and neck movements. Two identification methods have been applied to study the kinematics of head-neck movements of able-body as well as neck-injured subjects. In particular, sagittal plane movements are well modeled by a planar two-revolute-joint linkage. In fact, the motion in joint space seems to indicate that sagittal plane movements may be classified as a single DOF motion. Finally, a spatial three-revolute-joint system has been employed to model 3D head-neck movements.

Improving sequence-based fold recognition by using 3D model quality assessment

Motivation: The ability of a simple method (MODCHECK) to determine the sequence–structure compatibility of a set of structural models generated by fold recognition is tested in a thorough benchmark analysis. Four Model Quality Assessment Programs (MQAPs) were tested on 188 targets from the latest LiveBench-9 automated structure evaluation experiment. We systematically test and evaluate whether the MQAP methods can successfully detect native-likemodels. Results: We show that compared with the other three methods tested MODCHECK is the most reliable method for consistently performing the best top model selection and for ranking the models. In addition, we show that the choice of model similarity score used to assess a model's similarity to the experimental structure can influence the overall performance of these tools. Although these MQAP methods fail to improve the model selection performance for methods that already incorporate protein three dimension (3D) structural information, an improvement is observed for methods that are purely sequence-based, including the best profile–profile methods. This suggests that even the best sequence-based fold recognition methods can still be improved by taking into account the 3D structural information.

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.

Modeling ocean primary production: sensitivity to spectral resolution of attenuation and absorption of light

Modeling the vertical penetration of photosynthetically active radiation (PAR) through the ocean, and its utilization by phytoplankton, is fundamental to simulating marine primary production. The variation of attenuation and absorption of light with wavelength suggests that photosynthesis should be modeled at high spectral resolution, but this is computationally expensive. To model primary production in global 3d models, a balance between computer time and accuracy is necessary. We investigate the effects of varying the spectral resolution of the underwater light field and the photosynthetic efficiency of phytoplankton (α∗), on primary production using a 1d coupled ecosystem ocean turbulence model. The model is applied at three sites in the Atlantic Ocean (CIS (∼60°N), PAP (∼50°N) and ESTOC (∼30°N)) to include the effect of different meteorological forcing and parameter sets. We also investigate three different methods for modeling α∗ – as a fixed constant, varying with both wavelength and chlorophyll concentration [Bricaud, A., Morel, A., Babin, M., Allali, K., Claustre, H., 1998. Variations of light absorption by suspended particles with chlorophyll a concentration in oceanic (case 1) waters. Analysis and implications for bio-optical models. J. Geophys. Res. 103, 31033–31044], and using a non-spectral parameterization [Anderson, T.R., 1993. A spectrally averaged model of light penetration and photosynthesis. Limnol. Oceanogr. 38, 1403–1419]. After selecting the appropriate ecosystem parameters for each of the three sites we vary the spectral resolution of light and α∗ from 1 to 61 wavebands and study the results in conjunction with the three different α∗ estimation methods. The results show modeled estimates of ocean primary productivity are highly sensitive to the degree of spectral resolution and α∗. For accurate simulations of primary production and chlorophyll distribution we recommend a spectral resolution of at least six wavebands if α∗ is a function of wavelength and chlorophyll, and three wavebands if α∗ is a fixed value.

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/

A high-density immunoblotting methodology for quantification of total protein levels and phosphorylation modifications

The components of many signaling pathways have been identified and there is now a need to conduct quantitative data-rich temporal experiments for systems biology and modeling approaches to better understand pathway dynamics and regulation. Here we present a modified Western blotting method that allows the rapid and reproducible quantification and analysis of hundreds of data points per day on proteins and their phosphorylation state at individual sites. The approach is of particular use where samples show a high degree of sample-to-sample variability such as primary cells from multiple donors. We present a case study on the analysis of >800 phosphorylation data points from three phosphorylation sites in three signaling proteins over multiple time points from platelets isolated from ten donors, demonstrating the technique's potential to determine kinetic and regulatory information from limited cell numbers and to investigate signaling variation within a population. We envisage the approach being of use in the analysis of many cellular processes such as signaling pathway dynamics to identify regulatory feedback loops and the investigation of potential drug/inhibitor responses, using primary cells and tissues, to generate information about how a cell's physiological state changes over time.