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CB1954 is an attractive prodrug for directed-enzyme prodrug therapy (DEPT) and a conventional prodrug against tumors in which the enzyme NQO2 is highly expressed. We have determined the crystal structure of the NQO2−CB1954 complex to 2.0 Å resolution. The binding of the prodrug is governed by hydrophobic forces, while two key electrostatic contacts determine the specific orientation of the ligand. The structure also reveals an unfavorable interaction, therefore suggesting possible avenues for DEPT-tailored engineering studies.

Postoperative infections in abdominal and pelvic wounds after abdominal hysterectomy are mostly due to more than one organism, representing the wide range of anaerobic and aerobic bacteria present in the vagina of the asymptomatic female (Kauppila et al., 1983). Anaerobes, notably the Bacteroides species, may be found alone or in association with aerobes in 90 per cent of pelvic abscesses (Seligman, 1978). Researchers have been unable to demonstrate wound infections in animal models after inoculation of pure Bacteroides cultures and some doubt has been cast on the pathogenicity of this species. Kelly (1980), in a series of elegant experiments, demonstrated a pathogenic synergy between Escherichia coli and Bacteroides fragilis. When individually subinfective doses of these organisms were inoculated together into surgical wounds, severe sepsis resulted. Similarly, when peri-operative wound swabs cultured both aerobes and anaerobes the incidence of postoperative wound infection was 71 per cent compared to 13 to 22 per cent if anaerobes or aerobes were isolated singly. Infections caused by a combination of aerobic and anaerobic organisms are dependent on the presence of both and reduction of one kind of bacteria may preclude infection by the other. If either the anaerobic or aerobic population is decreased at the time of operation, there will be reduction in the rate of postoperative sepsis.

The basic equations of deflection, slope, and moments for a thin, flat, circular plate subjected to a uniform load on a concentric circle were derived for four generalized cases. From these generalized cases, six simplified cases were deduced. The four generalized cases have the uniform load acting on a concentric circle of the plate between the inner and outer edges, with the following boundary conditions: (a) Outer edge supported and fixed, inner edge fixed; (b) outer edge simply supported, inner edge free; (c) outer edge simply supported, inner edge fixed; and (d) outer edge supported and fixed, inner edge free.

The basic equations of deflection, slope, and moment for a thin, flat, circular plate, under a symmetrical variable load, for a constant force divided by the square of the radial distance, have been developed. Six cases have been derived. The first four cases cover the variable load acting over the entire plate, viz., (a) fixed, supported, outer edge and fixed, inner edge, (b) simply supported, outer edge and free, inner edge, (c) simply supported, outer edge and fixed, inner edge, (d) fixed, supported, outer edge and free, inner edge; and the final two cases are for a solid plate having the acting variable load bounded by circles of an inner radius and the outer support-load-radius; i.e., (e) fixed, supported, outer edge and (f) simply supported, outer edge.