A comprehensive computer simulation of drug metabolism and pharmacokinetics

A computer simulation program for pharmacokinetics has been further developed so as to include metabolic schemes for the 9 drugs at present included. The fate of a drug in a human subject is comprehensively represented and the quantitative effects of many factors on this fate may be assessed. The establishment of the simulations from experimental data is outlined and the applications of the program are discussed.     

Dislocation etch pits and growth of arsenic-antimony single crystals

Single crystals of an arsenic-antimony solid solution have been grown at the minimum melting point (612‡C) composition (25.5 at.% arsenic) where the solidus and liquidus touch. Pyramidal etch pits produced on (111) cleavage faces mark the sites of emergence of dislocations; dislocation densities are low, ranging between 10³ and 10⁵ per cm². The relationship between an unambiguous, right handed axial set and etch pit orientation on the (111) surface is established. The permissible Burgers vectors and dislocation reactions are detailed and are related to the observed etch pit types. In general, the results obtained also apply to the A7 structure elements themselves and amend previous findings of the crystallographic relationships between dislocation directions and etch pits.     

Mechanical and structural studies of low density polyethylene

This paper is one of a series concerned with the complete characterisation of the creep behaviour of oriented polymers, the correlation of creep behaviour with other mechanical properties and the interpretation of such data in the light of present structural knowledge. Sheets of oriented low-density polyethylene were prepared from initially isotropic sheets by cold-drawing, cold-drawing followed by heat-treatment at 55° C, drawing at a temperature of 55° C and hot-drawing at temperatures in the range 90 to 100° C. At each draw ratio, specimens were cut at angles of 0°, 45° and 90° to the draw direction. For each specimen, the variation of longitudinal and lateral strain with time, during uniaxial tensile creep at 20° C, was measured simultaneously by direct extensometer methods, for a wide range of applied stresses. All the materials exhibited complex anisotropic non-linear viscoelastic behaviour. The methods of presenting such data are discussed and the results are presented in some detail. Many similarities in the creep behaviour of the cold- and hot-drawn materials are noted. However, marked differences are apparent in the non-linearity and creep rate of the 45° specimens from these two materials at high draw ratio. These, and other effects found at high draw ratio, are discussed with reference to the structural studies reported in part 1. At low draw ratio, it is shown that the anomalous behaviour of the modulus in the draw direction, reported previously for cold-drawn material, may also be found in the hot-drawn material, although at a different creep time. On the basis of obvious differences in wide-angle X-ray patterns other workers had previously predicted that the anomalous mechanical behaviour of cold-drawn LDPE was probably unique. The anomalous behaviour of the hot-drawn material is also explained in terms of the structures discussed in part 1.     

Stabilized variant of Streptomyces subtilisin inhibitor and its use in stabilizing subtilisin BPN'

Protein protease inhibitors could potentially be used to stabilize proteases in commercial products such as liquid laundry detergents. However, many protein protease inhibitors are susceptible to hydrolysis inflicted by the protease. We have engineered Streptomyces subtilisin inhibitor (SSI) to resist proteolysis by adding an interchain disulfide bond and removing a subtilisin cleavage site at leucine 63. When these stabilizing changes were combined with changes to optimize the affinity for subtilisin, the resulting inhibitor provided complete protease stability for at least 5 months at 31 degrees C in a subtilisin-containing liquid laundry detergent and allowed full recovery of the subtilisin activity upon the dilution that occurs in a North American washing machine.     

Evolvable social agents for bacterial systems modeling

We present two approaches to the individual-based modeling (IbM) of bacterial ecologies and evolution using computational tools. The IbM approach is introduced, and its important complementary role to biosystems modeling is discussed. A fine-grained model of bacterial evolution is then presented that is based on networks of interactivity between computational objects representing genes and proteins. This is followed by a coarser grained agent-based model, which is designed to explore the evolvability of adaptive behavioral strategies in artificial bacteria represented by learning classifier systems. The structure and implementation of the two proposed individual-based bacterial models are discussed, and some results from simulation experiments are presented, illustrating their adaptive properties.     

The elastic constants of antimony-25.5 at. % arsenic alloy single crystals

The six independent elastic constants of single crystals of the homogeneous, minimum melting point alloy of composition antimony 74.5 at. % and arsenic 25.5 at. % have been measured. The elastic behaviour of the alloy is compared with that of the rhombohedral A7 structure elements arsenic and antimony and is found to show characteristics consistent with those expected for layer-type crystals. Elastic wave velocity surface cross-sections, particle displacement and energy flux vectors and Young's modulus are presented and discussed. The Debye temperature is 219 K.