In order to clarify the mechanism of action of quinolones against Staphylococcus aureus, GrlA and GrlB proteins of topoisomerase IV encoded by genes with or without mutations were purified separately as fusion proteins with maltose-binding protein in Escherichia coli. The reconstituted enzymes showed ATP-dependent decatenation and relaxing activities but had no supercoiling activity. The inhibitory effects of quinolones on the decatenation activity of topoisomerase IV were determined by quantitative electrophoresis with kinetoplast DNA as a substrate. The 50% inhibitory concentrations (IC50s) of levofloxacin, DR-3354, DU-6859a, DV-7751a, ciprofloxacin, sparfloxacin, and tosufloxacin against topoisomerase IV of S. aureus FDA 209-P were 2.3, 97, 0.45, 1.5, 2.5, 7.4, and 1.8 microg/ml, respectively, and were correlated well with their MICs. The IC50s of these drugs were from 2 to 20 times lower than those for the DNA gyrase. These results support genetic evidence that the primary target of new quinolones is topoisomerase IV in quinolone-susceptible strains of S. aureus. Three altered proteins of topoisomerase IV containing Ser-->Phe changes at codon 80 or Glu-->Lys changes at codon 84 of grlA, or both, were also purified. The inhibitory activities of quinolones against the topoisomerase IV which contained a single amino acid change were from 8 to 95 times weaker than those against the nonaltered enzyme. These results suggest that the mutations in the corresponding genes confer quinolone resistance.

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Electrical activation and structural defects in lattice-mismatched InGaAs/GaAs heterostructures are studied using the capacitance-voltage method, deep-level transient spectroscopy, and cross-sectional transmission electron microscopy. Confinement of structural defects is observed in an In0.2Ga0.8As/GaAs heterostructure with a relaxed InGaAs layer thicker than the thickness of the critical layer. When In composition is 0.2, where the lattice mismatch is 1.4% between InGaAs and GaAs, a two-dimensional growth mode dominates. Misfit dislocations are formed and conduction electrons are depleted only near the InGaAs/GaAs interface. Carrier depletion is related to an electron trap with an activation energy of 0.395 eV and a capture cross section of 1×10−16 cm2 induced by deformation. Electrical evaluations show that electrical activity in the InGaAs layer does not degrade by interfacial dislocations. Therefore, a good-quality InGaAs layer is provided though the thin layer near the interface is of poor quality. These results indicate that elastic strain is not large enough in this system for dislocations to rise to the surface. In an In0.4Ga0.6As/In0.2Ga0.8As/GaAs heterostructure, however, dislocation confinement is imperfect in spite of similar lattice mismatches between each of the interfaces. In this structure, threading dislocations rise into the epitaxial layer not only from the In0.4Ga0.6As/In0.2Ga0.8As interface but also from the In0.2Ga0.8As/GaAs interface. This indicates that dislocations can be generated in the layer that had already been formed during the growth of an upper layer.

We found a series of polymorphs with different colors in 2,5-diamino-3,6-dicyanopyrazine dyes. Their color difference was found to be caused by conformational change in the crystals, not by exciton interactions.

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