Screening mixtures for biological activity by NMR

Development of the new drugs often involves the screening of compound libraries for biological activity. Currently, the biologically active component can only be identified if either a pure compound is being tested or if the components of a mixture are spatially separated, for example, on beads. Here, we present an NMR technique based on the transferred nuclear Overhauser effect (transfer NOE) that allows identification and structural characterization of biologically active molecules from a mixture. As an example we demonstrate that from mixtures of oligosaccharides only alpha-L-Fuc-(1-->6)-beta-D-GlcNAc-OMe binds to Aleuria aurantia agglutinin. The sign of transferred NOEs is opposite to NOEs of small molecules that do not bind to the protein and, thus, an unequivocal identification of molecules with binding activity is possible. Normally, the selection of bound ligands is further facilitated in that the absolute intensity of transfer NOEs is much greater than that of NOEs of non-binding molecules. In addition, transfer NOEs provide information on the three-dimensional structure of the ligands in the bound state. Therefore, measuring transfer NOEs of mixtures of small molecules in the presence of large molecules, like proteins, should significantly enhance the options for screening mixtures of compounds for biological activity.     

Scientific and artistic investigation of multi-dimensional fractals on the AT & T pixel machine

The pipelined architecture and parallel organization of the AT&T Pixel Machine image computer are described and demonstrated with applications for the visualization of multidimensional fractals, particularly linear fractals and quaternion/ stacked Julia sets. Techniques for pushing the Pixel Machine to its peak abilities are described and apply to more recent parallel image computers as well.     

Bacteriophage lambda: transactivation, positive control and other odd findings

The purpose for this study was to evaluate the results of silicone oil use in patients who have undergone vitrectomy for proliferative vitreoretinopathy (PVR). The authors reviewed the 5-year results of 50 consecutive patients (52 eyes) with grade C1/D3 PVR operated on in 1987. Silicone oil has been removed in 42 eyes. The retina remained attached in 38 eyes. Visual acuities were finger counting in 12 eyes and 0.1 or greater in 19 eyes. Glaucoma was thought to be the major cause of loss of visual acuity after an initial improvement (9 eyes), as well as the most frequent complication of surgery (13 eyes). Silicone oil was deemed nonremovable in 10 operated eyes. A questionnaire was developed to determine the patients' perceptions of the use of silicone oil, and 46 patients responded to the questionnaire. Four patients indicated that they would not have elected to have surgery again. Six patients thought that surgery was not worthwhile, but would permit treatment again. Most patients thought that a modest amount of improvement had taken place and that vision was stable. Subjectively, most patients believed that surgery was worthwhile.     

Expression of laminin and nidogen genes during the postimplantation development of the mouse placenta

The expression patterns of laminin A, B1, B2, and nidogen genes were identified by in situ hybridization in postimplantation mouse extraembryonic tissues and maternal decidua during the period when the chorioallantoic placenta is established. Laminin and nidogen genes were not coordinately expressed either in the decidua or in trophoblast cells, indicating that these genes are regulated independently in these cell types during the establishment of the placenta. Laminin A mRNA was absent from the decidua except in the outer layer of cells adjacent to the myometrium and in the central decidual zone adjacent to the remnant of the uterine epithelium on Day 9. At this stage laminin B1, B2, and nidogen genes were strongly expressed in these cells and also in other regions of the decidua. Laminin B1 mRNA was present at higher levels in the decidua capsularis than in the decidua basalis, while nidogen mRNA showed highest expression in the decidua basalis. Laminin B2 mRNA was produced uniformly throughout the decidua at very high levels, suggesting that laminin B2 chains may be an important component of the decidual matrix. By Day 11, the nidogen gene was expressed only in endothelial cells lining the maternal blood spaces within the decidua. Laminin B1 and nidogen mRNAs were found at high levels within trophoblast giant cells at all stages, while laminin A mRNA was detected in trophoblast giant cells at later stages and laminin B2 mRNA was not produced in high levels by these cells. The patterns of gene expression show a very high degree of regional specialization, suggesting that the extracellular matrices in different regions of the decidua and extraembryonic membranes are likely to be composed of quite different ratios of laminin and nidogen polypeptides.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurements of single chain form factors by small-angle neutron scattering from polystyrene blends containing high concentrations of labelled molecules

A series of small angle neutron scattering measurements on blends of normal polystyrene (PSH) and labelled (deuterated) polystyrene (PSD) have been made with concentrations of PSD from 5 to 50 mol %. It is shown that the single chain form factor of the polymer in bulk can be obtained from a single concentration measurement for any concentration of labelled molecules, providing the molecular weights of the parent and labelled molecules are the same and the molecular weight distributions are narrow.