Acoustic experiments conducted over different tracks at the Atlantic Generating Station (AGS) site have shown significant transmission loss variability. These fluctuations cannot be accounted for entirely by bathymetric and water volume variations. Consequently, as suggested by previous studies, geoacoustic variations must be responsible for significant portions of the variability. We can take advantage of the relatively extensive core data that are available at the AGS site to model both the larger-scale range dependence and the smaller-scale variability. Uncertainties in the geoacoustic fields are modeled here by varying the vertical correlation length of the core profiles which changes the coefficients of representations by empirical orthogonal functions. The stochastic field representations are used for propagation modeling with both elastic and fluid sediments. Statistics of broadband signal transmission loss fluctuations are determined in terms of geoacoustic variabilities. Sensitivities of transmission loss predictions to frequency dependence of geoacoustic parameters are examined. Simulation statistics are compared with experimental data. [Work supported by ONR.]

The efficacy of empirical orthogonal functions (EOFs) in modeling ocean fluctuations for acoustic propagation predictions is well known, and recent work has demonstrated their advantages for sediment sound-speed variabilities. In this study, using EOFs for the direct estimation of sediment sound speed, density, and attenuation profiles is described, when relatively extensive data sets such as those from the Atlantic Generating Station (AGS) site are available. First, interpolations are generated based on minimizing mean-square errors. The resulting fields are appraised and compared thoroughly with those obtained from universal kriging, a method which is commonly employed by geostatisticians. Not only do the EOF interpolations have advantages in numerical efficiency, but also their construction is modified here to incorporate lateral terrain orientations as occur at the AGS site. Uncertainties in the geoacoustic fields are then modeled by stochastic variations in the EOF coefficients. The field representations are used for environmental input to propagation modeling of poro-elastic sediments in the AGS region. Statistics of transmission loss fluctuations are discussed in terms of geoacoustic variabilities. [Work supported by ONR.]

Future success for most pharmaceutical companies will depend on innovation leading to the discovery of new drugs that provide clear medical benefit to patients when compared to current therapies. There are three key steps in the discovery process; discovery of relevant biological targets, generation of 'lead' compounds and the optimization of leads to give potent, efficacious and safe drugs. There are, increasingly, many 'biological' approaches to treatment, such as gene therapy or antisense therapy. This article is focused solely on key aspects of lead generation for compounds of low molecular weight(1). Part 1 focuses on aspects of biological target identification. Part 2, to be published in the February issue of Drug Discovery Today, will address lead generation, with special emphasis on the measurement of diversity within and between compound libraries.

The contribution of individual basic amino acids within three putative "consensus sequences" for heparin binding of fibroblast growth factor-1 have been examined by site-directed mutagenesis. The results indicate that a significant reduction in the apparent affinity of fibroblast growth factor-1 for heparin is only observed when basic residues in one of the three regions are mutated. Mutation in the other regions are without affect on heparin binding. The heparin binding properties of synthetic peptides based on the three "consensus sequences" paralleled the mutagenesis results. That is, synthetic peptides corresponding to regions of the protein that were affected by mutagenesis with respect to heparin binding exhibited a relatively high affinity for immobilized heparin, whereas those corresponding to regions of similar charge density that were unaffected by mutagenesis did not. In addition, amino acid substitution of a nonbasic residue in the heparin-binding peptide could abolish its heparin binding capacity. The heparin-binding peptide could antagonize the mitogenic activity of FGF-1, probably because of the heparin dependence of this activity. Together these data demonstrate that the heparin binding properties of fibroblast growth factor-1 are dictated by structural features more complex than clusters of basic amino acids. The results of these and other studies indicate that consensus motifs for heparin-binding require further definition. More importantly, the results provide a basis for the design of peptide-based inhibitors of FGF-1.

The effects on low-frequency acoustic propagation resulting from ideal atmospheric flow over a large ridge are investigated using the parabolic approximation. The ridge is taken to be triangularly shaped with a horizontal earth-air interface on both sides. A Schwarz-Christoffel transformation is employed to calculate the wind speeds that are then used to compute the effective sound-speed profiles. These profiles are used by an implicit finite-difference implementation of the parabolic approximation to estimate the intensity of the sound field. Several examples are examined to determine the effects of this wind-modeling method on sound pressure levels over rigid earth-air boundaries. [Work supported by NASA.]