Antiherpesvirus activities of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine (A-5021) in cell culture

Antiherpetic activity of (1'S,2'R)-9-([1',2'-bis(hydroxymethyl)cycloprop-1'yl]methyl)guanine (A-5021) was compared with those of acyclovir (ACV) and penciclovir (PCV) in cell cultures. In a plaque reduction assay using a selection of human cells, A-5021 showed the most potent activity in all cells. Against clinical isolates of herpes simplex virus type 1 (HSV-1, n = 5) and type 2 (HSV-2, n = 6), mean 50% inhibitory concentrations (IC50s) for A-5021 were 0.013 and 0.15 microgram/ml, respectively, in MRC-5 cells. Corresponding IC50s for ACV were 0.22 and 0.30 microgram/ml, and those for PCV were 0.84 and 1.5 micrograms/ml, respectively. Against clinical isolates of varicella-zoster virus (VZV, n = 5), mean IC50s for A-5021, ACV, and PCV were 0.77, 5.2, and 14 micrograms/ml, respectively, in human embryonic lung (HEL) cells. A-5021 showed considerably more prolonged antiviral activity than ACV when infected cells were treated for a short time. The selectivity index, the ratio of 50% cytotoxic concentration to IC50, of A-5021 was superior to those of ACV and PCV for HSV-1 and almost comparable for HSV-2 and VZV. In a growth inhibition assay of murine granulocyte-macrophage progenitor cells, A-5021 showed the least inhibitory effect of the three compounds. These results show that A-5021 is a potent and selective antiviral agent against HSV-1, HSV-2, and VZV.     

A nontoxic adjuvant for mucosal immunity to pneumococcal surface protein A

In this study, we demonstrated that pneumococcal surface protein A (PspA) nasally administered with a nontoxic A subunit mutant of cholera toxin (mCT) S61F elicited a protective immune response. Immunization with PspA and mCT elicited higher levels of PspA-specific IgG and IgA Abs in serum and of IgG and IgA anti-PspA Ab-forming cells in spleens, cervical lymph nodes (CLN), and lung tissue when compared to nonimmunized mice. Furthermore, significant PspA-specific IgA Abs were induced in saliva and nasal secretions. These responses were dependent on the use of mCT as a mucosal adjuvant. The PspA-specific Ab responses induced by mCT S61F were comparable with those induced by native CT (nCT). Analysis of cytokine responses showed that nasal PspA plus mCT S61F enhanced the induction of PspA-specific CD4+ T cells producing IL-4 but not IFN-gamma in CLN at both the protein and mRNA levels. Importantly, significant numbers of mice intranasally immunized with PspA plus mCT S61F were protected from lethal challenge with capsular serotype 3 Streptococcus pneumoniae A66. These results show that intranasal administration of PspA together with mCT S61F is an effective mucosal vaccine against pneumococcal infection and induces CD4+ Th2-type cells, which provide help for both mucosal and systemic Ab responses.     

Statistical-Thermodynamics Modeling of Clathrate-Hydrate-Forming Systems Suitable as Working Media of a Hydrate-Based Refrigeration System

Attempts to develop a novel hydrate-based refrigeration system have been carried out in recent years. It was reported that the vapor/liquid/liquid/hydrate four-phase equilibrium conditions in the systems of cyclopentane and water plus difluoromethane satisfy the required conditions of the working media of a hydrate-based refrigeration system for residential air-conditioning use. When a statistical- thermodynamic model is applied to the above-mentioned hydrate-forming systems, the Kihara potential parameters of these guest substances need to be determined. In this study, an attempt was made to determine the Kihara potential parameters of difluoromethane and cyclopentane based on phase equilibrium data for difluoromethane + water, cyclopentane + water, and difluoromethane + cyclopentane + water systems. The absolute average deviations of the predicted equilibrium pressure at a given temperature from the corresponding experimental values are 0.043 for the HFC-32 + water system, 0.12 for the cyclopentane + water, and 0.031 for the HFC-32 + cyclopentane + water.     

Subtype selectivity of a new alpha 1-adrenoceptor antagonist, JTH-601: comparison with prazosin

The existence of alpha 1-adrenoceptors with low affinity for prazosin (alpha 1L group: alpha 1L and alpha 1N subtypes) has been proposed in addition to alpha 1-adrenoceptor subtypes with high affinity for prazosin (alpha 1H group: alpha 1A, alpha 1B and alpha 1D subtypes). A newly synthesized alpha 1-adrenoceptor antagonist, JTH-601 (N-(3-hydroxy-6-methoxy-2,4,5-trimethylbenzyl)-N-methyl-2-(4-hydro xy-2-isopropyl-5-methyl-phenoxy) ethylamine hemifumarate) showed approximately a 10 times higher affinity for the alpha 1L group, a similar affinity for the alpha 1A subtype, but a more than 10 times lower affinity for the alpha 1B and alpha 1D subtypes when compared with prazosin. These results provide a further pharmacological evidence that alpha 1-adrenoceptors with low affinity for prazosin exist in addition to those with high affinity for prazosin, suggesting that JTH-601 may be useful for characterising the alpha 1-adrenoceptor subtypes.     

Preparation of Crystallized Sr1−XCaXMoO4 Solid-Solution Films by an Electrochemical Method at Room Temperature and Their Luminescence

A complete series of well-crystallized solid-solution Sr_{1– X} -Ca_XMoO₄ films has been prepared on molybdenum substrates in an electrolytic solution containing Sr²⁺ and Ca²⁺ ions by an electrochemical method at room temperature (25°C). The peak positions of excitation and emission of the Sr_1–XCa_XMoO₄ solid-solution films were independent of the Ca content: 285 ± 2 nm for excitation and 536 ± 2 nm for emission at liquid-nitrogen temperature (−196°C).     

Morphology of microporous neosepta ion-exchange membranes and its effect on separation of biological mixtures

Specially prepared microporous Neosepta ion-exchange membranes were investigated to establish a correlation between their structural characteristics (pore-size distribution, porosity) and permeability to components of immunoglobulin (Ig) fractions of mouse ascitic fluids. The solutions to be separated contained IgG₁ with specificity to horseradish peroxidase or to the heavy chain of human IgM, some other proteins, and a large amount of ammonium sulfate (0.22–0.35M). Analysis of the membrane morphology carried out by scanning electron microscopy and mercury porosimetry showed that the membranes possess a polymodal pore-size distribution. There are large open pores (400–600 and 200–300 nm in diameter) on the membrane surfaces, but the void volume of the membranes is a system of connected pores of smaller diameters (from 60–100 to 7–10 nm). The main part of the pores in the membranes displaying the best separation ability was 8–17 nm in diameter. It was found that highly porous charged membranes (relative porosity 58–60%) with low ion-exchange capacity (0.02–0.1 meq/g) made it possible to achieve the desired desalination degree of protein mixture (80–83%) within 5–7 h instead of 5 days needed in the traditional dialysis. Moreover, the amount of separated accompanying proteins reached 25–30% depending on membrane porosity and the quality of specific IgG₁ was considerably improved. © 1995 John Wiley & Sons, Inc.     

Narrow-bandgap a-Ge:H/a-Si:H multilayers for amorphous silicon-based solar cells

Precisely defined multilayers consisting of a-Ge:H wells and a-Si:H barrier layers have been prepared and characterized as a new type of narrow-bandgap materials for amorphous silicon-based solar cells. It is found that the optical and electrical properties of the layered structures are dramatically improved compared to bulk a-Si_1−ξGe_x:H alloy, being explained by the quantum confinement effects in the ultra-thin a-Ge:H wells. The light-induced changes in the photoconductivity is also remarkably reduced for the multilayers.     

Analysis of polychlorinated biphenyls in transformer oil by using liquid-liquid partitioning in a microfluidic device

Polychlorinated biphenyls (PCBs) that are present in transformer oil are a common global problem because of their toxicity and environmental persistence. The development of a rapid, low-cost method for measurement of PCBs in oil has been a matter of priority because of the large number of PCB-contaminated transformers still in service. Although one of the rapid, low-cost methods involves an immunoassay, which uses multilayer column separation, hexane evaporation, dimethyl sulfoxide (DMSO) partitioning, antigen-antibody reaction, and a measurement system, there is a demand for more cost-effective and simpler procedures. In this paper, we report a DMSO partitioning method that utilizes a microfluidic device with microrecesses along the microchannel. In this method, PCBs are extracted and enriched into the DMSO confined in the microrecesses under the oil flow condition. The enrichment factor was estimated to be 2.69, which agreed well with the anticipated value. The half-maximal inhibitory concentration of PCBs in oil was found to be 0.38 mg/kg, which satisfies the much stricter criterion of 0.5 mg/kg in Japan. The developed method can realize the pretreatment of oil without the use of centrifugation for phase separation. Furthermore, the amount of expensive reagents required can be reduced considerably. Therefore, our method can serve as a powerful tool for achieving a simpler, low-cost procedure and an on-site analysis system.     

A finite element LES for high-Re flow in a short-elbow pipe with undisturbed inlet velocity

The paper is concerned with a large-eddy simulation (LES) for a high-Reynolds-number flow in a short-elbow pipe, which can potentially be employed in the primary piping system of the Japan Sodium-cooled Fast Reactor (JSFR). The basic performance of the LES is studied for an elbow pipe flow without turbulence at inlet boundary at Re = 1.2 × 10⁶ by comparison with a flow observed in a 1/3-scale water experiment, where the flow disturbance at the pipe inlet is small. In setting up the computational conditions, special care was taken to ensure that the mesh subdivision was suitable for the simulation of the pipe flow through a theoretical consideration. We discuss the effects of the turbulence model (Smagorinsky model, WALE model) and the inlet velocity profile on the results. The mechanism of the pressure fluctuation and the origin of the fluid force are also discussed with the aid of spectral analysis and the visualization of essential hydraulic quantities.