Biomedical subjects

David A Gough

Publications and source records attributed to David A Gough.

5 recordsLinked to original sources

PubMed2003

Tissue window chamber system for validation of implanted oxygen sensors.

An experimental system is described for validating electrochemical oxygen sensors implanted in tissues. The system is a modified hamster window chamber in which a thin layer of vascularized tissue is held between two plates, one plate having an observation window and the other plate having an array of oxygen sensors. This arrangement permits simultaneous recording of oxygen sensor signals and nondestructive visualization of the tissue adjacent to the sensors over periods of 1 mo or more, without the inhibitory effects of anesthesia. The system provides a means for study of the effects of spatial and temporal oxygen distributions on the sensor signals and adaptation of the tissue structure over time. Examples are given of sensor recordings and images of tissues with implanted oxygen sensor arrays.

Animals↗

PubMed2003

Whole-proteome interaction mining.

MOTIVATION: A major post-genomic scientific and technological pursuit is to describe the functions performed by the proteins encoded by the genome. One strategy is to first identify the protein-protein interactions in a proteome, then determine pathways and overall structure relating these interactions, and finally to statistically infer functional roles of individual proteins. Although huge amounts of genomic data are at hand, current experimental protein interaction assays must overcome technical problems to scale-up for high-throughput analysis. In the meantime, bioinformatics approaches may help bridge the information gap required for inference of protein function. In this paper, a previously described data mining approach to prediction of protein-protein interactions (Bock and Gough, 2001, Bioinformatics, 17, 455-460) is extended to interaction mining on a proteome-wide scale. An algorithm (the phylogenetic bootstrap) is introduced, which suggests traversal of a phenogram, interleaving rounds of computation and experiment, to develop a knowledge base of protein interactions in genetically-similar organisms. RESULTS: The interaction mining approach was demonstrated by building a learning system based on 1,039 experimentally validated protein-protein interactions in the human gastric bacterium Helicobacter pylori. An estimate of the generalization performance of the classifier was derived from 10-fold cross-validation, which indicated expected upper bounds on precision of 80% and sensitivity of 69% when applied to related organisms. One such organism is the enteric pathogen Campylobacter jejuni, in which comprehensive machine learning prediction of all possible pairwise protein-protein interactions was performed. The resulting network of interactions shares an average protein connectivity characteristic in common with previous investigations reported in the literature, offering strong evidence supporting the biological feasibility of the hypothesized map. For inferences about complete proteomes in which the number of pairwise non-interactions is expected to be much larger than the number of actual interactions, we anticipate that the sensitivity will remain the same but precision may decrease. We present specific biological examples of two subnetworks of protein-protein interactions in C. jejuni resulting from the application of this approach, including elements of a two-component signal transduction systems for thermoregulation, and a ferritin uptake network.

Algorithms↗

PubMed2003

Frequency characterization of blood glucose dynamics.

Examples of the frequency range of blood glucose dynamics of normal subjects and subjects with diabetes are reported here, based on data from the literature. The frequency band edge was determined from suitable, frequently sampled blood glucose recordings using two methods: frequency domain estimation and signal reconstruction. The respective maximum acceptable sampling intervals, or Nyquist sampling periods (NSP), required to accurately represent blood glucose dynamics were calculated. Preliminary results based on the limited data available in the literature indicate that although blood glucose NSP values are higher in most diabetic subjects, values in some diabetic subjects are indistinguishable from those of normal subjects. High fidelity monitoring sufficient to follow the intrinsic blood glucose dynamics of all diabetic subjects requires a NSP of approximately 10 min, corresponding to a continuous frequency band edge of approximately 1 x 10(-3) Hz. This analysis provides key information for the design of clinical studies that include blood glucose dynamics and for the design of new glucose monitoring systems.

Blood Glucose↗

PubMed2002

School-based violence prevention programs: systematic review of secondary prevention trials.

OBJECTIVE: To quantify the effectiveness of school-based violence prevention programs for children identified as at risk for aggressive behavior. DESIGN: Systematic review and meta-analysis of randomized controlled trials. Electronic databases and bibliographies were systematically searched and authors and organizations were contacted to identify randomized controlled trials. Standardized, weighted mean effect sizes were assessed by meta-analysis. SETTING: Elementary, middle, and high schools. PARTICIPANTS: Children at risk for aggressive behavior. MAIN OUTCOME MEASURES: Violent injuries, observed or reported aggressive or violent behaviors, and school or agency responses to aggressive behaviors. RESULTS: Of the 44 trials identified, none reported data on violent injuries. For the 28 trials that assessed aggressive behaviors, the pooled difference between study groups was -0.36 (95% confidence interval, -0.54 to -0.19) in favor of a reduction in aggression with intervention. For the 9 trials that reported data on school or agency responses to aggression, the pooled difference was -0.59 (95% confidence interval, -1.18 to 0.01). Subgroup analyses suggested greater effectiveness in older students and when administered to mixed-sex groups rather than to boys alone. CONCLUSIONS: School-based violence prevention programs may produce reductions in aggressive and violent behaviors in children who already exhibit such behavior. These results, however, need to be confirmed in large, high-quality trials.

Adolescent↗

PubMed2002

A new method to estimate ligand-receptor energetics.

In the discovery of new drugs, lead identification and optimization have assumed critical importance given the number of drug targets generated from genetic, genomics, and proteomic technologies. High-throughput experimental screening assays have been complemented recently by "virtual screening" approaches to identify and filter potential ligands when the characteristics of a target receptor structure of interest are known. Virtual screening mandates a reliable procedure for automatic ranking of structurally distinct ligands in compound library databases. Computing a rank score requires the accurate prediction of binding affinities between these ligands and the target. Many current scoring strategies require information about the target three-dimensional structure. In this study, a new method to estimate the free binding energy between a ligand and receptor is proposed. We extend a central idea previously reported (Bock, J. R., and Gough, D. A. (2001) Predicting protein-protein interactions from primary structure. Bioinformatics 17, 455-460; Bock, J. R., and Gough, D. A. (2002) Whole-proteome interaction mining. Bioinformatics, in press) that uses simple descriptors to represent biomolecules as input examples to train a support vector machine (Smola, A. J., and Schölkopf, B. (1998) A Tutorial on Support Vector Regression, Neuro-COLT Technical Report NC-TR-98-030, Royal Holloway College, University of London, UK) and the application of the trained system to previously unseen pairs, estimating their propensity for interaction. Here we seek to learn the function that maps features of a receptor-ligand pair onto their equilibrium free binding energy. These features do not comprise any direct information about the three-dimensional structures of ligand or target. In cross-validation experiments, it is demonstrated that objective measurements of prediction error rate and rank-ordering statistics are competitive with those of several other investigations, most of which depend on three-dimensional structural data. The size of the sample (n = 2,671) indicates that this approach is robust and may have widespread applicability beyond restricted families of receptor types. It is concluded that newly sequenced proteins, or those for which three-dimensional crystal structures are not easily obtained, can be rapidly analyzed for their binding potential against a library of ligands using this methodology.

Drug Design↗