Structure-based design of cathepsin K inhibitors containing a benzyloxy-substituted benzoyl peptidomimetic

Peptidomimetic cathepsin K inhibitors have been designed using binding models which were based on the X-ray crystal structure of an amino acid-based, active site-spanning inhibitor complexed with cathepsin K. These inhibitors, which contain a benzyloxybenzoyl group in place of a Cbz-leucine moiety, maintained good inhibitory potency relative to the amino acid-based inhibitor, and the binding models were found to be very predictive of relative inhibitor potency. The binding mode of one of the inhibitors was confirmed by X-ray crystallography, and the crystallographically determined structure is in close qualitative agreement with the initial binding model. These results strengthen the validity of a strategy involving iterative cycles of structure-based design, inhibitor synthesis and evaluation, and crystallographic structure determination for the discovery of peptidomimetic inhibitors.     

An Overview of Progress in the Design And Implementation of Landsat-D Systems

Landsat-D will be launched in late 1981 or early 1982 into a Sun-synchronous orbit near 700 km. Landsat-D systems and the principal observing instrument, the Thematic Mapper, are being designed and implemented to provide a significantly improved Earth-resources monitoring capability. The Thematic Mapper will have seven spectral bands (0.45-0.52, 0.52-0.60, 0.63-0.69, 0.76-0.90, 1.55-1.75, 2.08-2.35, and 10.5-12.5 ?m), with an instantaneous field of view at nadir of 30 m except for the thermal band (120 m). The data from the Thematic Mapper and other Landsat-D flight segment systems will be relayed to the Landsat-D ground data processing system using a direct readout capability or the Tracking and Data Relay Satellite System and communications satellites. The ground systems will process the data as it arrives at rates up to 100 Mbit/s and a total volume of 2.6 × 1011 bit/day into standard digital and photographic products within 48 hours of data acquisition. This includes 200 Multispectral Scanner Subsystem and 100 Thematic Mapper scenes per day. The Thematic Mapper increased spatial, spectral, and radiometric resolution should be of primary benefit in agricultural and vegetation surveys, but substantial improvements in resource and land cover observations for geology, land use, and water resources applications are also to be anticipated.     

Effects of different doses of apomorphine on the glutamate decarboxylase activity of the substantia nigra and the medial basal hypothalamus

The activity of gamma-aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD, EC 4.1.1.15) was assayed in the rat substantia nigra (SN) and medial basal hypothalamus (MBH) following systemic injection of different doses of the dopamine receptor agonist apomorphine. In SN, the highest dose of apomorphine (1000 micrograms/kg) causes an increase of the GAD activity whilst an opposite effect is observed with the lowest dose (35 micrograms/kg). Results obtained in SN are in accordance with previous neurochemical and behavioural data suggesting an opposite action of high (500 micrograms/kg) and low doses (100 micrograms/kg) of apomorphine in nigro-striatal system, probably due to the existence of two classes of dopamine receptors, i.e. classical postsynaptic dopamine receptors and presynaptic inhibitory dopamine autoreceptors. In MBH, the evidence for similar effects of low and high doses of apomorphine (the decrease of GAD activity) may suggest that, as already reported, at this level only one class of dopamine receptors is present.     

Letter: Electrical method of detecting optimum time to inseminate

Recently translated studies of the electrical resistance of cervical mucus as a test for the optimum time of insemination of agricultural animals are reviewed. The technique involves the measurement of the electrical conductivity of the surface of the mucosa in the vaginal vestibule. Experiments with cows and sows have shown that pregnancy or fertilization rates are considerably higher when mucosal electrical resistance is low at the time of insemination than when resistance is high. It has also been demonstrated in sows that mucosal resistance is higher in pregnant than in nonpregnant animals. Further research into these results is recommended.     

Sex and the single hemisphere: specialization of the right hemisphere for spatial processing

Specialization of the right hemisphere for spatial processing was studied in 200 normal boys and girls between 6 and 13 years of age. Boys performed in a manner consistent with right hemisphere specialization as early as the age of 6. Girls showed evidence of bilateral representation until the age of 13. The results suggest a sexual dimorphism in the neural organization underlying cognition during a major period of childhood. The results, which have implications for reading instruction, are discussed in terms of a possible sex difference in neural plasticity during development and the clinical consequences of such a difference.     

A time-space tradeoff for sorting on non-oblivious machines

A model of computation is introduced which permits the analysis of both the time and space requirements of non-oblivious programs. Using this model, it is demonstrated that any algorithm for sorting n inputs which is based on comparisons of individual inputs requires time-space product proportional to n².