Simulation of a pneumatic hand crane for work support was developed for system design. The crane's mathematical model consists of a pneumatic cylinder model, a crane link model, and a controller that includes a human model to passively operate the hand crane by operating force. The human model's inverse system learns using a neural network. The feasibility of the simulation was demonstrated in comparison with measurement results from operating force and acceleration.

Bacillus brevis 47 secreted vast amounts of protein into the medium and had a characteristic three-layered cell wall. The three layers are designated, from the outermost to the innermost layer, as the outer wall (4.2 nm), the middle wall(8.5 nm), and the inner wall (2.1-3.7 nm). The inner wall might be a peptidoglycan layer. The fine cell wall structure was morphologically altered to various extents, depending on the growth period. At the early stationary phase of growth, cells began to shed the outer two layers of a limited area of the surface. This shedding was complete after further cell growth. The morphological alterations in the cell wall occurred concomitantly with a prominent increase in protein excretion. When protein secretion was severely inhibited by growing cells with Mg2+, morphological alterations in the cell wall were not observed, even at the late stationary phase of growth. This was also the case with a nonprotein-producing mutant, strain 47-5-25. When cells were incubated in buffers, the outer two layers of the cell wall were specifically removed, leaving cells surrounded only by the inner wall layer. The layers removed by incubation were recovered by high-speed centrifugation. This fraction consisted of two layers resembling the outer and middle wall layers. Protein secreted by B. brevis 47-5 consisted mainly of two proteins with approximate molecular weights of 150,000 and 130,000. Proteins released by incubating cells in buffers and proteins in the outer- and middle-wall-enriched fraction were also composed mainly of two proteins with the same molecular weights as those secreted into the medium. Therefore, we conclude that B. brevis 47 secretes proteins derived from the outer two layers of cell wall and these components are synthesized even after the shedding of the outer two layers.

DX-9065a had a good correlation between linear pharmacokinetics and pharmacodynamics after intravenous administration in humans.

The bactericidal activity of M14659 against Escherichia coli in low-iron environments was investigated and compared with that of ceftriaxone and ceftazidime. The bactericidal activity of M14659 against E. coi in Mueller-Hinton broth was enhanced 30-to 20,000-fold by addition of transferrin, which is an iron-binding protein, whereas the activity of ceftriaxone or ceftazidime was much less strongly affected. This enhancement by transferrin was completely inhibited by saturating the iron-binding capacity of transferrin with FeCl3.

In vitro and in vivo antifungal activities of D0870 were evaluated in comparison with those of fluconazole. D0870, which is the R-enantiomer of IC1195,739, was found to be the mycologically active enantiomer by comparing the activities of D0870 with those of M16355 (S-enantiomer of IC1195,739). D0870 showed a broad spectrum of antifungal activity and MICs and minimum antibiotic concentrations 4-to 2,000-fold lower in synthetic amino acid medium (fungal) agar than those of fluconazole for various fungi. Although MICs of D0870 were affected by variation of the test conditions, such as type of medium, inoculum size of fungi, supplementation with fetal bovine serum, and pH of medium, they were consistently much lower than those of fluconazole under any condition. In vivo activities of D0870 in the systemic infection models with Candida albicans, Cryptococcus neoformans, and Aspergillus fiumigatus in normal mice and in the mice immunosuppressed with cyclophosphamide or cortisone acetate were 2-to 7-fold and 3-to 89-fold greater than those of fluconazole, respectively. In these infection models in immunosuppressed mice, the therapeutic efficacy of D0870 was almost equivalent to that in normal mice, whereas the efficacy of fluconazole was 2-to 50-fold lower than that in normal mice.It has been reported that the recent rise in the number of patients with systemic fungal infections closely relates to therapy using immunosuppressive or anticancer agents (6, 7). These kinds of agents reportedly cause the destruction of the cellular or humoral host defense system, and that destruction inevitably raises the frequency of opportunistic infections caused by fungi such as Candida, Aspergillus, or Cryptococcus species. Under these circumstances, the need for potent systemic antifungal agents has been increasing recently. Six systemic antifungal agents, amphotericin B (AMPH), flucytosine, miconazole (MCZ), ketoconazole, fluconazole (FCZ), and itraconazole, have been developed so far for clinical use. However, the clinical values of these agents have been limited primarily by their relatively high risks of toxicity, emergence of drug resistance, pharmacokinetic deficiencies, and/or insufficiency of their antifungal activities (7,8,14). Thus, much effort still has been made to develop novel potent antifungal agents which are safe and systemically effective against various deep-seated mycoses. D0870 (Fig. 1) is the R-enantiomer of IC1195,739, which has excellent in vitro and in vivo antifungal activities (4,16 In vitro antifungal activity. MICs and minimum antibiotic concentrations (MACs) were determined by the twofold agar dilution method with synthetic amino acid medium (fungal)