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.     

Isoflurane and sevoflurane augment norepinephrine responses to surgical noxious stimulation in humans

BACKGROUND: Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. METHODS: Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. RESULTS: Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. CONCLUSION: The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.     

Acceptor specificity of cellobiose phosphorylase from Cellvibrio gilvus: synthesis of three branched trisaccharides

Cellobiose phosphorylase from Cellvibrio gilvus was examined for its acceptor specificity in the synthetic reaction with glucose-1-phosphate, using substrates in which the C-6 substituent of D-Glc had been altered. A range of disaccharides were also tested for acceptor specificity but only those with (1-->6)-linkages were successful acceptors. Melibiose, gentiobiose, isomaltose and also the monosaccharide glucuronamide were found to react with cellobiose phosphorylase and glucose-1-phosphate giving beta-D-Glcp-(1-->4)-[alpha-D-Galp-(1-->6)]-D-Glcp, beta-D-Glcp-(1-->4)-[beta-D-Glcp-(1-->6)]-D-Glcp, beta-D-Glcp-(1-->4)-[alpha-D-Glcp-(1-->6)]-D-Glcp and beta-D-Glcp-(1-->4)-D-GlcUNp, respectively. These products were purified using a range of chromatographic methods and characterised by NMR and FAB-MS. This is the first time cellobiose phosphorylase has been shown to synthesise trisaccharides.     

In vivo analysis of hydrogen peroxide and lipid radicals in the striatum of rats under long-term administration of a neuroleptic

It has been hypothesized that free radicals play a causative role in tardive dyskinesia, which is an inveterate movement disorder caused by chronic administration of neuroleptics. To verify this hypothesis, rats were reared while being regularly treated with water containing a neuroleptic, haloperidol (HPD), for 1 year (HPD group). The changes in the striatal hydrogen peroxide content of the rats in the HPD and control groups were measured by using a Pt-disk microelectrode while the animals were in a freely moving state following intraperitoneal administration of HPD (HPD challenge). We also performed electron spin resonance (ESR) detection of lipid radicals in the striatum before the HPD challenge. HPD challenge led to significant elevation of the intrastriatal hydrogen peroxide in all animals, but the elevation in the HPD group was smaller than that in the control group. However, in the HPD group, marked ESR signals of intrastriatal lipid radicals were observed. We think that these results support the hypothesis on the role of free radicals in tardive dyskinesia.     

Free-air CO2 enrichment (FACE) net nitrogen fixation experiment at a paddy soil surface under submerged conditions

The aim of this study was to evaluate the cumulative net free-living nitrogen (N) fixation and its response to elevated atmospheric carbon dioxide (CO₂) in the submerged surface of paddy soil. The study site was an actual paddy area in central Japan that was equipped with a free-air CO₂ enrichment (FACE) facility and was composed of four bays, where each bay had an elevated CO₂ plot (FACE plot) and an ambient plot. Field incubation was conducted at subplots without N fertilizer application from May 28 to August 18, 2012 (82 days). The CO₂ enrichment was an average of +528 ppm during the study period at the subplots. The changes in total N (TN) content in the surface soil (0–1 cm) were determined in comparison to the initial TN content. The cumulative net N fixations during the 82-day study period were 47.1 ± 3.7 and 43.3 ± 5.8 (standard error) kg N ha^?1 in the FACE and ambient plots, respectively. The difference between the FACE and ambient plots was not significant (p = 0.05). However, these values were partly affected by the charophyte blooms, which are not involved in N fixation. The results are not conclusive, and the one bay without charophyte blooming displayed a significant increase in the cumulative net N fixation (approximately 10 kg N ha^?1) with CO₂ enrichment (p < 0.001).     

Silver Iodide Formation in Methyl Ammonium Lead Iodide Perovskite Solar Cells with Silver Top Electrodes

Silver is a low‐cost candidate electrode material for perovskite solar cells. However, in such cells the silver electrodes turn yellow within days of device fabrication. The color change is also accompanied by a dramatic decrease in the power conversion efficiency when compared to otherwise identical devices using gold electrodes. Here, it is shown that the color change results from silver oxidation to silver iodide, due to a reaction with iodine in methyl ammonium lead perovskite. The change in X‐ray diffraction and X‐ray photo­electron spectroscopy is discussed. Exposure to air accelerates corrosion of the Ag electrodes when compared to dry nitrogen gas exposure. However, iodine not reacted with silver is observed by X‐ray photoelectron spectroscopy even for the perovskite solar cell kept in dry nitrogen gas. It is proposed that silver iodide is formed when methyl ammonium iodide migration is facilitated by the small pinholes in the hole transport layer spiro‐MeOTAD.     

Sliding behavior of metallic glass: Part I. Experimental investigations

The unlubricated sliding characteristics of zirconium-based bulk metallic glass disks have been examined in vacuum and in air using sliders made from the same material or from a hard bearing steel (52100). The pin-on-disk test system allowed collection of debris, monitoring of the friction force and, using a Kelvin probe, in situ detection of changes in the structure and chemical composition of the disk surface. Post-test characterization included microhardness testing, X-ray diffraction, SEM and EDS. Examination of worn surfaces, cross-sections and debris confirmed the importance of plastic deformation, material transfer and environmental interactions. When devitrified material was tested, sliding processes caused the near-surface material to re-amorphize. Results from sliding of bulk metallic glass specimens were compared with those from related experiments involving crystalline metals and alloys. Although bulk metallic glasses are reported to have only limited ductility in tensile tests, the friction coefficients and worn surfaces of these materials are typical of ductile materials.     

Gate control, surface leakage currents, and peripheral charging in AlGaN/GaN heterostructure field effect transistors having nanometer-scale schottky gates

Gate control properties together with gate leakage currents in AlGaN/GaN heterostructure field effect transistors (HFETs) with nanometer-scale Schottky gates were investigated, focusing on the effects of AlGaN surfaces at the gate periphery. Fabricated AlGaN/GaN HFETs showed unexpectedly small gate length (L_G) dependence of transconductance, g_m. Comparing the transfer characteristics from theory and experiment, effective L_G values in the fabricated devices were found to be much longer than the geometrical size on the order of 100 nm, indicating the formation of virtual gates. Detailed analysis of the gate leakage current behaviors based on a thin surface barrier model showed the presence of a strong electric field at the gate periphery. The mechanism of the virtual gate formation was discussed based on the obtained nanometer-scale Schottky gate behaviors.     

Difference in antigen presentation pathways between cortical and medullary thymic epithelial cells

Antigen presentation by thymic epithelial cells (TEC) to T cells that undergo maturation is one of the major events in the selection of the T cell repertoire. We have already reported that medullary TEC lines (mTEC) established from newborn C57BL/6 (H-2b) mice are able to present a soluble antigen, ovalbumin (OVA), to OVA-specific, I-Ab restricted helper T cell lines but cortical TEC (cTEC) lines are not (Mizuochi, T. et al., J. Exp. Med. 1992. 175: 1601). In this report, to clarify the cause of this difference, we analyzed the biochemical nature as well as the distribution of both major histocompatibility complex (MHC) class II molecules and invariant chains (Ii) in both TEC by immunoprecipitation and laser confocal scanning microscopic analysis, as well as the expression of mRNA encoding H-2Ma or H-2Mb. Our results demonstrate that cTEC and mTEC are both able to present peptide antigens to peptide-specific, I-Ab-restricted helper T cell hybridoma and are able to present class II MHC alloantigens to an I-Ab-specific T cell line, that mRNA for H-2Ma and H-2Mb are expressed in both TEC, that cTEC and mTEC apparently incorporate tetramethylrhodamine isothiocyanate-labeled OVA in the same manner, and that the SDS-stable MHC class II molecules, onto which peptides were loaded, are formed in both cTEC and mTEC. However, these molecules were more rapidly degraded in mTEC than in cTEC. In addition, two Ii-derived polypeptides of approximately 21 kDa and 10 kDa were precipitated by the anti-class II monoclonal antibody Y3P; 10-kDa polypeptides were detected in the both TEC, while 21-kDa polypeptides were detected only in cTEC. Finally, beta chains of MHC class II with less sialylated oligosaccharides were precipitated from the cell surface of cTEC. Taken together, these results suggest that there are substantial differences in the antigen-presenting pathways of cTEC and mTEC, and these difference might be responsible for T cell selection events in the thymus.