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Mass spectrometry (MS) is increasingly used in clinical medicine in Japan. In contrast to the successful application of MS in clinical microbiology, the adoption of MS-based assays for routine testing in clinical chemistry is very slow. In order to promote the significant benefits that MS platforms bring to laboratory medicine and patient care, the Japanese Society for Biomedical Mass Spectrometry (JSBMS) initiated a medical mass spectrometrist (MMS) certification program in 2013. As of Dec 2018, 308 persons from various medical specialties have been certified. We believe that they will play significant roles for expanding routine clinical MS usage in Japan.

Previous studies have established the unexpected monoamine oxidase-B (MAO-B) substrate properties of racemic 3-methyl-6-phenyl-3-aza-bicyclo[4.1.0]heptane, the 3,4-cyclopropyl analog of the achiral proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The two stereocenters present in this compound provide an opportunity to examine the enantioselectivity and diastereoselectivity of the MAO-B-catalyzed ring α-carbon oxidation of cyclic tertiary amines to give the corresponding conjugated iminiumyl metabolites. This paper reports the results of such stereochemical studies using expressed human MAO-B as the catalyst.

The use of antipsychotic drugs is limited by their tendency to produce extrapyramidal movement disorders such as tardive dyskinesia and parkinsonism. In previous reports it was speculated that extrapyramidal side effects associated with the butyrophenone neuroleptic agent haloperidol (HP) could be caused in part by the neurotoxic effect of its pyridinium metabolite (HPP(+)). Although both HPP(+) and HP have been shown to induce neurotoxic effects such as loss of cell membrane integrity, no information exists about the difference in the neurotoxic potency, especially in the potency to induce plasma membrane damage, between these two agents. In the present study, we compared the potency of the interaction of HPP(+) and HP with the plasma membrane integrity in the rat brain. Membrane permeabilization (assessed as [(18)F]2-fluoro-2-deoxy-d-glucose-6-phosphate release from brain slices) and fluidization (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl 1,3,5-hexatriene) were induced by HPP(+) loading (ator=100 microM andor=10 microM, respectively), while comparable changes were induced only at a higher concentration of HP (=1 mM). These results suggest that HPP(+) has a higher potency to induce plasma membrane damage than HP, and these actions of HPP(+) may partly underlie the pathogenesis of HP-induced extrapyramidal side effects.

We established a method for determining capsaicin glucuronide in rat urine samples using liquid chromatography-mass spectrometry combined with enzymatic hydrolysis. Capsaicin was not detected in urine samples of rats administered capsaicin intraperitoneally (i.p., 2 and 4 mg/kg), but after hydrolysis with β-glucuronidase, extraction with methanol and solid-phase extraction, capsaicin was clearly detected by liquid chromatography-mass spectrometry with electrospray ionization. The limit of detection was obtained to be 0.1 ng/ml in urine sample matrix. The conditions for the enzymatic hydrolysis of the conjugate were optimized for β-glucuronidases from Ampullaria, Escherichia coli, bovine liver, Helix pomatia and Patella vulgata. The optimal conditions among those examined [pH (3.3-9.0), temperature (37-70°C) and enzyme amount (50-2500 U)] for 1 ml of the urine sample were as follows: β-glucuronidase from Ampullaria (pH 4.2, 45°C, 500 U), from Escherichia coli (pH 6.0-7.2, 37°C, 500 U), from bovine liver (pH 5.0, 45°C, 500 U), from Helix pomatia (pH 5.0, 60°C, 1250 U) and from Patella vulgata (pH 3.8, 45-60°C, 2500 U). Among the enzymes examined, β-glucuronidase from Ampullaria was found to be suitable for hydrolysis of the conjugate. Under the optimal conditions of Ampullaria β-glucuronidase, the incubation of 1 ml of urine sample for 90 min was sufficient for hydrolysis of capsaicin glucuronide in the urine sample. The urinary recovery values of capsaicin collected for 0-48 hr after administration of 2 and 4 mg/kg capsaicin to rats were 1.4 and 1.1%, respectively.

In this study, we investigated the effect of vesicular zinc on ischemic neuronal injury. In cultured neurons, addition of a low concentration (under 100 µM) of zinc inhibited both glutamate-induced calcium influx and neuronal death. In contrast, a higher concentration (over 150 µM) of zinc decreased neuronal viability, although calcium influx was inhibited. These results indicate that zinc exhibits biphasic effects depending on its concentration. Furthermore, in cultured neurons, co-addition of glutamate and CaEDTA, which binds extra-cellular zinc, increased glutamate-induced calcium influx and aggravated the neurotoxicity of glutamate. In a rat transient middle cerebral artery occlusion (MCAO) model, the infarction volume, which is related to the neurotoxicity of glutamate, increased rapidly on the intracerebral ventricular injection of CaEDTA 30 min prior to occlusion. These results suggest that zinc released from synaptic vesicles may provide a protective effect against ischemic neuronal injury. Keywords:: zinc, ischemia, glutamate, middle cerebral artery occlusion, CaEDTA

We have determined three opioidmimetics (compounds I-III) in the rat brain dialysates after intraperitoneal (i.p.) administration of compounds I-III using a liquid chromatography/mass spectrometry with tandem mass spectrometry (LC-MS/MS). The dialysate samples with methanol were directly analyzed by online column-switching liquid chromatography. Using multiple reaction monitoring (MRM, product ions m/z 421 of m/z 657 for compound I, m/z 421 of m/z 643 for compound II, and m/z 407 of m/z 629 for compound III) on LC-MS/MS with electrospray ionization (ESI), opioidmimetics in rat brain dialysates were determined. Calibration curves of the method showed a good linearity in the range of 10-100 ng/ml for each compound. The limit of determination was estimated to be ca. 1 ng/ml for compounds II and III, and ca. 5 ng/ml for compound I, respectively. The precision of analysis showed coefficients of variation ranging from 4.7 to 10.4% at compound III concentration (10-100 ng/ml) in Ringer's solution. As a result, the procedure proved to be very suitable for routine analysis. The method was applied to the analysis of three opioidmimetics in the brain dialysate samples from rats treated with these compounds.

Medium-chain acyl-coenzyme A (CoA) esters are key metabolites in lipid metabolism. Liquid chromatography-electrospray ionization mass spectrometry analysis of medium-chain acyl-CoA esters is described. Eight medium-chain acyl-CoA esters were well separated on a C(8)-MS reversed-phase column using a linear gradient of ammonium acetate buffer (pH 5.3)-acetonitrile. The positive-ion mass spectra of all the saturated and unsaturated medium-chain acyl-CoA esters gave dominant [M+H](+) ions, whereas their negative-ion mass spectra showed abundant [M-H](-) and [M-2H](2-) ions. The positive-ion mode of operation was slightly less sensitive than the negative-ion detection mode. Five medium-chain acyl-CoA esters of C(6:0), C(8:0), C(8:1), C(10:0), and C(10:1) in liver, heart, kidney, and brain from the mouse were identified. The predominant acyl-CoA peaks were C(6:0), C(8:0), and C(10:0). Small amounts of medium-chain acyl-CoAs of C(8:1) and C(10:1) were detected only in heart and kidney. The analytical method is very useful for the analysis of medium-chain acyl-CoA esters in the tissues.

The inhibitory effects of quinolone antimicrobial agents and nonsteroidal anti-inflammatory drugs on purified mouse liver mitochondrial medium chain acyl-CoA synthetase catalyzing the first reaction of glycine conjugation were examined, using hexanoic acid as a substrate. Enoxacin, ofloxacin, nalidixic acid, diflunisal, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid, which do not act as substrates, were potent inhibitors. Diflunisal, nalidixic acid, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid inhibited competitively this medium chain acyl-CoA synthetase with K(i) values of 0.6, 12.4, 19.6, 13.4, and 15.0 microM, respectively. Enoxacin and ofloxacin inhibited this medium chain acyl-CoA synthetase in a mixed-type manner with K(i) values of 23.7 and 38.2 microM, respectively. Felbinac, which is a substrate, inhibited the activity of this medium chain acyl-CoA synthetase for hexanoic acid (IC50 = 25 microM). The concomitant presence of enoxacin and felbinac strongly inhibited this medium chain acyl-CoA synthetase. These findings indicate that medium chain acyl-CoA synthetases may be influenced by quinolone antimicrobial and nonsteroidal anti-inflammatory drugs.

To understand the periodic conservative component of sliding friction force for atomically-flat nanosized contact areas, we have investigated an interfacial potential energy surface responsible for sliding of a two-dimensional rigid atomic cluster on a periodic potential surface and moire-like misfit dislocation net patterns in the contact area. We found that especially when the misfit parameter (ratio) α between lattice constants of the contacting surfaces is close to 1.0, the interfacial potential energy surface varies depending strongly on the lattice misfit angle θ and the size of the contact area, resulting in changes in the misfit dislocation net pattern.

Multilayer epitaxy with a W-VO2 top layer over a bottom layer of which the crystal phase depends on the starting oxygen flow, was done on a-Al2O3(110) by reactively sputtering a V-W (1.6 at.% wt.) ...

We have investigated the potential of high-performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) to determine enrichments of citrulline as a marker for in vivo nitric oxide (NO) production in brain tissue. The analysis of citrulline as the butyl ester derivative was evaluated using two types of ionization: electron spray ionization (ESI) and atmospheric pressure chemical ionization (APCI). APCI-MS appeared to be more suitable for determination of citrulline than ESI-MS, because the ion intensity of the protonated molecule ion [M+H]+, m/z 232, of citrulline in the former was about twelve times higher than in the latter. The chromatography was carried out on a reversed C8 column with the mobile phase consisting of 15% acetonitrile: 85% H2O: 0.2% acetic acid (v/v). The calibration curve had good linearity within the concentration range investigated (5 ng to 500 ng/ml). The limit of determination was estimated to be ca. 1 ng/ml of standard solution. The method was applied to the analysis of citrulline in the brain dialysate obtained from rat after perfusion of the striatum with haloperidol (HP, 0.1 mM). It is concluded that APCI-MS in combination with HPLC can be successfully applied to determination of citrulline in brain tissue, thus providing a useful tool for assessment of in vivo NO production.

Singly charged cations of silver atoms and clusters (Agn+, n=1,3,5,7,9) were deposited on highly oriented pyrolytic graphite substrates at well-controlled, various collision energies. The total amount of Ag atoms remaining on the substrates after collision was quantified by measuring the Ag 3d5/2 photoelectron intensities. The collision energy dependence of the amount of deposited Ag atoms revealed that, for all the species, there are three distinct energy regions, for which soft landing, rebounding, or implantation is a dominant process, and that the energy ranges for the processes strongly depend on the cluster size. The deposition efficiency vs collision energy curve for each cluster is well fitted to that for Ag1, by considering the difference between the contact area of Ag1 with the surface and that of the cluster, reflecting the compactness of the clusters. Boundaries between the different deposition regimes for the clusters were less distinct than those for Ag1. Considering anisotropy in shape of a...

The relative importance of the liver and kidney for glycine conjugation of ortho-substituted benzoic acids was investigated. Glycine conjugation of ortho-substituted benzoic acids was investigated in mouse liver and kidney mitochondria. The extent of glycine conjugation of benzoic acids with the halogen group decreased in the order F > Cl > Br > I. The conjugation of salicylic acid with glycine took place in only the kidney. 2-Methoxybenzoic acid exhibited no activity in the liver and kidney. The difference in glycine conjugation of ortho-substituted benzoic acids was observed between liver and kidney. The kidney was more active in glycine conjugation of ortho-substituted acids than the liver. In addition, the relationship between glycine conjugation and the chemical structure of ortho-substituted acids was examined in the liver and kidney. The size of the substituent had a far greater influence over glycine conjugation in the liver and kidney. Glycine conjugation was also dependent on the substituent electronegativity. It may be important that the substrates undergoing glycine conjugation contain a flat region coplanar to the carboxylate group.

Silver monomer (Ag+1) or heptamer (Ag+7) ions were deposited on highly oriented pyrolytic graphite (HOPG) substrates at various, well-controlled collision energies. The total amount of silver (Ag) atoms remaining on the substrates after the collision was examined by measuring the Ag 3d5/2 photoelectron intensities. The collision energy dependence of the number of deposited Ag atoms revealed that there exist, for both species, three well-defined energy regions, for which soft landing, rebounding, or implantation is a dominant process. It was found that the collision energy dependence for Ag7 is well scaled to that for Ag1 by the factor 1/72/3 rather than 1/7, reflecting the compactness of Ag7.

Silver nanoclusters, generated and size-selected in the gas phase and soft landed on low-temperature glassy carbon substrates, were characterized by real-time X-ray photoelectron spectroscopy (XPS). It has been found that the 3d core–electron binding energies of the deposited clusters gradually decrease with time in size-specific manners. The observation clearly showed that the clusters are deposited intact on the surface and diffuse and aggregate, leading to larger clusters. This demonstrates that the real-time XPS can provide key information on states and behaviors of size-selected nanoclusters deposited on surfaces.

We report detailed study of surface-induced dissociation (SID) of small carbon cluster negative ions (Cn-, n = 5−12) in collision with Si substrates. Fragment mass spectra have been observed in the collision energy range of 0−10 eV/atom. Neutral C3 loss occurred at collision energies lower than 2 eV/ atom. In the medium energy range (2−6 eV/atom), a marked even−odd difference in the dissociation has been observed: even fragment ions were predominantly generated from incident odd clusters, whereas both even and odd fragment ions from incident even clusters. These results are qualitatively in good agreement with the formation energies of fragment ion−neutral pairs calculated using the experimentally determined binding energies of ions and neutrals. At elevated collision energies (6−10 eV /atom), further fragmentation and electron detachment from fragment ions occurred and smaller cluster ions with even n were preferentially generated.

Glycine conjugation of a series of benzoic acid derivatives was investigated in mouse kidney mitochondria. The chlorine and methyl substitutions in the para- and meta-positions of the benzene ring yielded an increase in glycine conjugation. The acids with a methoxy group showed a low degree of glycine conjugation. In addition, the acids with nitro or amino groups were conjugated to a slight extent with glycine. The in vitro conjugation of salicylic acid with glycine occurred not in liver but in kidney. The specificity of the renal medium chain acyl-CoA synthetase catalyzing the first reaction of glycine conjugation was also examined. The enzyme accepted not only medium chain fatty acids but also aromatic and arylacetic acids. The highest activity was shown with hexanoic acid. High activities were observed for benzoic acid derivatives with alkyl and alkoxyl groups in the para- and meta-positions of the benzene ring. An ortho-substituted acid exhibited no activity. In addition, the enzyme was less active with valproic acid, tranexamic acid, indomethacin and ketoprofen. The enzyme was inhibited by diflunisal, 2-hydroxydodecanoic acid and salicylic acid, which did not act as substrates. There was a poor correlation between the activity of the medium chain acyl-CoA synthetase and glycine conjugation of eleven substituted benzoic acids. These findings suggest that the present medium chain acyl-CoA synthetase is involved in glycine conjugation of the substituted acids in mouse kidney mitochondria, but there may be a larger contribution of another isoenzyme.

To investigate the relationship between CYP2D6 genotypes (reported to be associated with the susceptibilities to Parkinson’s disease and multisystem atrophy) and the possible susceptibility to neuroleptic malignant syndrome (NMS) and subacute myelo-optico-neuropathy (SMON), we analyzed the CYP2D6 gene by polymerase chain reaction and restriction fragment length polymorphism in Japanese schizophrenia patients with a history of NMS. There was no significant difference in the frequency of the poor metabolizer genotype of CYP2D6 between the cases with a history of NMS and controls (p > 0.05). The frequency of the mutation located at the HhaI site in exon 6 of CYP2D6 in the cases was higher, but not significantly (p > 0.05; the mutated allele frequency was 0.25), than that in the controls, schizophrenia patients without NMS (0.11) and healthy controls (0.09). The frequency (0.10) of the HhaI mutation type in patients with a diagnosis of SMON was also not significantly higher than in healthy controls. These results suggest that the poor metabolizer and HhaI polymorphism of CYP2D6 may not be a useful molecular marker for predicting the onset of NMS and SMON.

A simple, rapid, and sensitive method which allows us to simultaneously determine bromvalerylurea (BVU) and its three metabolites (3-methylbutyrylurea [MVU], alpha-(cystein-S-yl)isovalerylurea [CVU], and alpha-(N-acetylcystein-S-yl)isovalerylurea [AcCVU]) was investigated by frit-fast atom bombardment liquid chromatography-mass spectrometry (frit-FAB LC-MS). The LC-MS analysis was performed after the solid-phase extraction from tissue and urine samples with a Sep-Pak C18 cartridge. Tissue homogenates and urine were adjusted to pH 4.0 and applied to the cartridges. The retained BVU and its metabolites were eluted from the cartridge with 2 mL of acetonitrile/10 mM ammonium acetate buffer (pH 3.5, 50:50, v/v). The eluate was analyzed by LC-MS, which employs a semimicro type L-column ODS column. The proposed conditions are as follows: mobile phase A, 0.4% glycerol in acetonitrile/10 mM ammonium acetate buffer (pH 3.5) (5:95, v/v); mobile phase B, 0.4% glycerol in acetonitrile; elution mode, linear gradient, 100% A (5 min) to 100% B in 15 min; flow rate, 0.2 mL/min; split ratio, 1:40. Extraction recoveries of BVU and its metabolites were 91.90-97.79% from the spiked liver homogenate and 89.68-96.13% from the spiked urine. The detection limits ranged from 10 to 25 ng/g in selected ion monitoring mode.

Hemispherical and specular transmittance in visible wavelength region and small-angle neutron-scattering of silica aerogels were measured to investigate the effects of supercritical drying media and heat treatment on the optical properties and structure of them. Silica aerogels were prepared by using methanol, ethanol, 2-propanol and carbon dioxide as supercritical drying medium. The analysis of transmission spectra suggested that a reduction of transmittance in visible light can be attributed to Rayleigh scattering, and the scattering intensity depended on the supercritical drying medium. The difference of the scattering intensity among the samples was related to the difference of the cluster size of aerogels from the results of small angle neutron scattering. Heat treatment affected the scattering intensity, but the change of the cluster size was not observed.

Amino acid conjugation is an important route of detoxification of xenobiotic and endogenous carboxylic acids. The specificity of the purified medium chain acyl-CoA synthetase catalyzing the first reaction of amino acid conjugation was investigated further for substrates and inhibitors. Molecular modeling techniques were applied to derive the molecular characteristics of substrates and inhibitors for the medium chain acyl-CoA synthetase. The purified enzyme accepted not only straight medium chain fatty acids but also aromatic acids. Of the arylacetic acids, activity was obtained with naphthylacetic acids, whereas introduction of a methyl group at the α-position caused loss of activity. High activity was also observed with cyclohexanoic acid. Diflunisal, 2-hydroxydodecanoic acid, and nalidixic acid inhibited the medium chain acyl-CoA synthetase activity for hexanoic acid, with K i values of 0.8, 4.4, and 12.3 μM, respectively. The inhibitory carboxylic acids were competitive with respect to hexanoic acid. The hydroxyl or ketone (oxo) groups at the β-position of carboxylic acids were an important determinant for inhibitory activity. All substrates and inhibitors contained a flat hydrophobic region coplanar to the carboxylate group. In addition, the substrates had negative values for charge on the carbon in the β-position of carboxylic acids.

We have evaluated the neuronal uptake of 12 neutral and quaternary azaheterocyclic amines that are possible candidates for idiopathic Parkinson's disease via dopamine transporter of striatal synaptosomes. The double-reciprocal plots for dopamine transporter obtained from Wistar rat and C57BL/6 mouse synaptosomes with N-methyl-4-phenylpyridinium cation (MPP+) as a substrate were identical to each other. Neutral beta-carbolines and tetrahydroisoquinolines were unfavorable substrates for dopamine transporter. The quarternization of these compounds strikingly increased the affinity for dopamine transporter with 2-10 times greater Km and 10 times smaller Vmax values than MPP+. Although catechol tetrahydroisoquinolines were weak substrates, their quarternization reduced their original properties as substrates for dopamine transporter. These results provide both topographic and electrogenic information of azaheterocyclic amines for the dopamine transporter-mediated influx. The intramolecular distance between the N-atom and the centroid of the benzene ring could be an important factor for the recognition of binding site of dopamine transporter, and an adequate net charge similar to dopamine would be further required for translocation into the cells.

Previous studies have suggested that during forebrain ischemia, considerable Zn2+ is released from synaptic vesicles of gultamatergic neuronal terminals and accumulates in hippocampal CA1 pyramidal neurons, leading to delayed neuronal death. However, since a time lag exists between the accumulation of Zn2+ and the occurrence of ischemia and there are conflicting reports about the amount of Zn2+ released, the level of released Zn2+ during ischemia in vivo is still unclear. In this study, we investigated the temporal change of extracellular Zn2+ in the hippocampal CA1 area using microdialysis and the accumulation of Zn2+ in hippocampal CA1 neurons with TSQ staining in rats with a transient forebrain ischemia. The level of extracellular Zn2+ in the CA1 area increased transiently reaching a peak 15 min after occlusion, then decreased with time, returning to the basal level 15 min after reperfusion. In addition, at this peak, the level of extracellular Zn2+ was about twice the basal level. Assessment of the intracellular Zn2+ in hippocampal neurons with TSQ revealed that Zn2+ accumulate at 24 h, but not 0 and 6 h after ischemia. These results suggest that, although the synaptic vesicular Zn2+ is released into the synaptic cleft during ischemia in vivo, the amount of released Zn2+ might not be so excessive, and it does not accumulate in hippocampal CA1 pyramidal neurons immediately after ischemia.

Copyright (c) 1997 Elsevier Science B.V. All rights reserved. Pb doped (10 mol%) TiO 2 thin films, by sol-gel dip-coating method, are prepared for a novel low-cost solid-state heterojunction solar cell (n-Pb x Ti 1−x O 2 /p-CuInSe 2 ) application. X-ray diffraction (XRD) results show the films to be polycrystalline, single phase anatase (A) type with crystals oriented mostly in A(1 0 1) plane, up to 700°C annealing temperature. At 900°C, presence of rutile (R) phase is also observed. Scanning electron micrographs show nano-crystalline porous structure of the films with particles of uniform size and shape. Auger analysis shows incorporation of Pb into TiO 2 and its depth profile indicates uniform distribution of Pb, Ti and O along the thickness of the film. Photoluminescence (PL) measurements show a shift in the PL spectrum of TiO 2 towards longer wavelength region as it is doped with Pb, suggesting a decrease in the band gap, due to the incorporation of Pb into TiO 2 lattice.

For full understanding of the optical properties of alumina ceramics which are used as a substrate of thin film c-Si solar cells, we carried out computer simulations of diffuse reflectance and measurements of angle-resolved reflectance. As the result of the computer simulations, we obtained a theoretical expression for the reflectance properties of alumina ceramics with flat surface. The expression can be applied for the measured reflectance of alumina ceramics with rough surface when an effect of surface condition was taken into account.

The network structure of silica aerogels heated at 300, 400 and 500°C in dried air have been determined by neutron total scattering measurements using a pulsed spallation neutron source. SANS experiments were also performed to obtain the particle size of the silica constituting aerogel. The elementary particle size obtained is about 13A in diameter. The distances of the Si-O and O-O interactions in such fine silica particles are 1.61 and 2.64 A, respectively, which are the same as those of fused silica. The coordination numbers of these pairs are found to be less evident than those of fused silica. In addition, the distances of the Si-Si pairs in the aerogels are slightly longer than that of fused silica. According to the heat treatment temperature, the coordination numbers of the Si-O and O-O interactions increase and the distance of the Si-Si pair decreases. These results indicate that although the network structure of fine silica particles treated at lower temperature is loose and imperfect, such structure can be changed by heating at relatively low temperature. The Raman spectra and the skeletal density measurements of the aerogels support also these results.

The alumina particles have been generated by a magnetron sputtering — gas aggregation method. The analyses of transmission electron microscope (TEM) images and electron diffraction patterns revealed some of the particles are tiny crystals of θ-alumina. The dependence of the particle size on the geometry and the temperature of the source exit has been studied.

Pure and Pb doped TiO 2 semiconductor thin films are deposited on single crystal Si (100) surface by a simple sol-gel method with a Pb content of 5, 10 and 15 mol%, under different temperatures (550, 750 and 850°C). The crystal structure, surface morphology and optical properties of the films, deposited on a Si (100) surface, have been studied using X-ray diffraction (XRD), scanning electron microscopy (SEM) and photoluminescence (PL) spectroscopy, respectively. XRD patterns indicate the amorphous/nanocrystalline nature of the films together with the presence of pure anatase (A) to an anatase/rutile (A/R) mixture as the temperature increases from 550°C to 850°C. The surface morphology of the films reveal a porous structure with particle size in the range of 15 nm to 100 nm. An intense green photoluminescence is observed in the visible region for pure TiO 2 and the intensity gradually decreases by doping with lead, at all deposition (550, 750 and 850°C) and measuring (4.2, 77 and 300 K) temperatures.

Recently we have sucessfully developed, 1) the apparatus to select a size of clusters, which is generated by laser ablation and innert gas aggregation techniques, by a TOF mass spectrometer with an ion reflector and a mass gate, 2) the machine to generate mass selected cluster flux with high density by CORDIS (Cold Reflex Discharge Ion Source), gas filled multi cooling stages consisted of Q-pole, and mass selection filters by means of Q-mass spectrometer, and 3) the apparatus to generate highly densed ionized cluster flux by Ar discharged magnetron sputtering gun operated under about 1,000 Pa He as an aggregation gas, to study deposition of cluster flux with and/or without a kinetic energy onto substrate for a fabrication of a complex quantum confined nano structure on any substrate by using clusters as building blocks.In this paper, the main characteristics of above three apparatuses and some of the recent preliminary experimental results are summarized. And the prospects of this new attempt are discussed after reviewing the latest progresses of computer simulation on “soft landing” and “hard collision” by cluster impacts onto a crystal substrate by our colaborative laboratory.

Molecular characteristics of carboxylic acids were investigated for the ability to inhibit a purified medium chain acyl-CoA synthetase, using hexanoic acid as a substrate. Salicylic acid, 4-methylsalicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxyoctanoic acid, which do not act as substrates for the medium chain acyl-CoA synthetase, were potent as inhibitors. Valproic acid was not an inhibitor. Salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxyoctanoic acid inhibited the medium chain acyl-CoA synthetase with Ki values of 37, 5.2, and 500 μM, respectively. 4-Methylsalicylic acid was more potent than salicylic acid. The inhibitory carboxylic acids were competitive with respect to hexanoic acid. The distance of the hydroxyl group from the carboxylic acid group of the benzene ring influenced the inhibitory activity. The hydroxyl group on the carbon adjacent to the carboxylic acid group was required for inhibitory activity. In addition, there was a good correlation between the lipophilicity of the carboxylic acids and the Ki values, suggesting that the lipophilicity of the carboxylic acids is a major determinant for inhibition of the medium chain acyl-CoA synthetase.

We present our preliminary attempt to produce a low cost and efficient solar cell based on TiO2. Pb doped TiO2 thin films are prepared by sol-gel method with a Pb content of 5, 10 and 15 mol%, in order to reduce the band gap of TiO2 such that the semiconductor responds to the visible region of the solar spectrum. Films are deposited on silicon, quartz, and conducting (ITO coated) glass substrates under different temperature conditions. X-ray diffraction study shows an amorphous to polycrystalline nature of the film as the deposition is carried over layer by layer. UV-visible transmittance patterns do indicate a lowering in the band gap of Pb doped TiO2 films. Preliminary surface analysis by SEM and photo-electrochemical (PEC) measurements of the films have also been made.

The effects of a pyridinium metabolite (HPP+) derived from haloperidol (HP) on in vivo tyrosine hydroxylation was evaluated in freely moving rats. As an index of the in vivo activity of tyrosine hydroxylase (TH), the rat striatum was perfused with NSD-1015, and extracellular 3,4-dihydroxyphenylalanine (DOPA) levels were measured. HPP+ (1 mM) gradually reduced tyrosine hydroxylation to 30% of the basal level, although the effect was less potent than 1-methyl-4-phenylpyridinium ion (MPP+). On the contrary, HPP+ at a 0.1 mM dose decreased in 5-hydroxyindoleacetic acid (5-HIAA) level, but did not affect dopamine metabolites. The present study revealed that HPP+ irreversible inhibited in vivo tyrosine hydroxylation by the same manner of MPP+. However, the neurotoxic effects of HPP+ in vivo would be selective for serotonergic over dopaminergic neurons, which distinguishes the toxic profile of this compound compared to that of MPP+.

Energy-dispersive X-ray diffraction experiments of molten KCl under high pressure have been carried out by using synchrotron radiation. The diffraction profiles of molten KCl were acquired just above the melting temperature of KCl up to 4 GPa. The reduced structure factor S(Q)'s for molten KCl do not show any change in their primary features, except for a gradual increase in the first peak intensity with increasing pressure. This implies that molten KCl does not show a first-order phase transition, such as the B1-B2 transition, found in solid KCl, but that the local structure in molten KCl must be changed by compression. According to a molecular-dynamics simulation, this change of S(Q) can be explained by a continuous increase in the coordination number of the nearest-neighbor ions in molten KCl with pressure.

Hydrophobic interactions sometimes play an important role in enzymatic reactions. In order to interpret such reaction data on the basis of comparative molecular field analysis (CoMFA) some method of introducing lipophilic parameters is necessary, since in the conventional CoMFA approach only electrostatic and steric fields are included in the original version. In the present study, the idea of Molecular Lipophilicity Potential (MLP) was introduced into the original CoMFA algorithm and the glycine conjugation reactions were analyzed. The conjugation data used were the whole reaction of glycine conjugation as well as the initial step of the reaction where substrates bind to coenzyme CoA. The substrates used include aromatic as well as aliphatic carboxylic acids. The CoMFA approach can explain data of aromatic and aliphatic carboxylic acids with a single model, whereas the multiple linear regression (MLR) analysis affords separated results for these two kinds of carboxylic acids. Thus, wide applicability of the CoMFA approach is supported and the aromatic and aliphatic carboxylic acids are suggested to behave in a common fashion in the conjugation reaction of the first process.

Polymer matrix composites have sometimes been used for shielding electro magnetic interference (EMI). In order to make clarify the effects of the fiber volume fraction of the composites on creep phenomenon, the creep behavior during 3-point bending creep tests was investigated at various constant temperatures. The material used had stainless steel fiber conductive fillers and a metamorphic poly-phenylene ether matrix. Three fiber volume fractions were 0.73, 1.52 and 2.39%. The master curves of creep compliance were obtained by applying the Arrhenius reciprocation laws of time and temperature for all materials. The shapes of the 3 master curves were found to be the same, being shifted on the time axis and on the creep compliance axis. Therefore it was concluded that creep behavior of the materials depended mainly on the viscoelastic property of the matrix resin and also depended not only on time and temperature, but also on fiber volume fraction.

Silica alcogels prepared from tetramethylorthosilicate were supercritically dried with methanol, ethanol, 2-propanol and carbon dioxide media. The density, transmittance, specific surface area and pore size of the aerogels obtained were compared. The supercritical drying media affects the properties of the aerogel.

Liquid chromatography combined with pneumatically assisted electrospray (ion spray) mass spectrometry was evaluated for the characterization of low-molecular-mass compounds such as a variety of substituted benzoic acids and their glycine conjugates. Each substituted benzoic acid and its glycine conjugate formed with rat liver mitochondria were separated with a conventional C8 packed column or a semimicro C8 column using three mobile phases. The positive- and negative-ion mass spectra of the glycine conjugates gave abundant [M + H]+ and [M − H]− ions, respectively. However, the positive-ion mass spectra of the acids were dominated by [M + H − H2O]+ ions, with the exception of [M + H]+ ions for acids having an amino, an acetylamino or a dimethylamino group. All of the negative-ion mass spectra of acids gave dominant [M − H]− ions. The negative-ion mass spectra of acids with halogen, nitro and cyano groups showed the ions equivalent to the mass of each functional group. Further, the alkoxyl group gave a characteristic fragmentation representing loss of the alkyl moiety. The abundances of the fragment ions due to the functional groups gave information on the position of the ring substituents in the negative-ion mass spectra. The positive- and negative-ion mass spectra of the glycine conjugates revealed the presence of glycine.

A possible aerobic degradative pathway for polyacrylate was examined with trimer (1,3,5-pentane tricarboxylic acid; PTCA)-utilizing bacteria. A few metabolic products from PTCA accumulated in culture filtrates and reaction mixtures of washed cells. Fraction A was detected as a main metabolite by high-performance liquid chromatography. A small amount of fraction B was concomitant with fraction A. Another fraction, C, was also detected. These compounds were suggested by liquid chromatography-mass spectrometry analyses to be 1,3,5-(1- or 2-pentene)tricarboxylic acid (fraction A or B) and 1,3,5-(2-oxopentane)tricarboxylic acid (fraction C). Fraction A was quickly further metabolized by washed cells, but fraction B was only gradually degraded. From these results, the metabolic pathway for polyacrylate is suggested to be quite similar toβ-oxidation for saturated fatty acids. The degradation of PTCA by washed cells was slower than that by growing cells and was inhibited by 5 mM NaN3. This suggests that the metabolism is linked to a respiratory chain or energy-producing system of bacteria which can aerobically assimilate PTCA.

A simple and rapid method for the detection of 12 quaternary ammonium compounds (Suxamethonium, Pancuronium, Benzethonium, Acetylcholine, Bethanechol, Hexamethonium, Propantheline, Methylbenactyzium, Neostigmine, Distigmine, Pyridostigmine and Ambenonium) using thermospray high-performance liquid chromatography (LC)-mass spectrometry was investigated. Each compound was extracted from urine as an ion-pair with bromothymol blue, tropaeolin OO and hexanitrodiphenilamine in dichloromethane. The used LC column was Asahipak GS-320H for aqueous steric exclusion chromatography, and the mobile phase was 100 mM ammonium acetate-acetonitrile (90/10 v/v or 70/30 v/v). The ion source block and tip heater temperatures were set at 300 and 320°C, respectively. The vaporizer control temperature was kept at the temperature of the take off temperature minus 15°C. The recoveries of 12 quaternary ammonium compounds from the spiked urine were 76.1 to 98.6% by ion-pair extraction. The detection limits of these compounds for the simultaneous analysis were 0.5-80 ng/ml by selected ion monitoring mode.

A series of substituted benzoic acids and their glycine conjugates were characterized by liquid chromatography—atmospheric pressure chemical ionization mass spectrometry. Each substituted benzoic acid and its glycine conjugate were separated with a Cosmosil 5 C8 column using three mobile phases. All negative-ion mass spectra of the substituted benzoic acids gave abundant [M  H]− and [M  COOH]− ions. For acids with halogen, nitro, cyano, and acetylamino groups, fragmentations corresponding to losses equivalent to the mass of each functional group were also observed. In addition, the alkoxyl group gave a characteristic fragmentation representing loss of the alkyl moiety. The abundances of the fragment ions due to the functional groups gave information on the position of the ring substituents. All of the positive- and negative-ion mass spectra of the glycine conjugates gave abundant [M + H]+ and [M  H]− ions with characteristic fragment ions, respectively. Fragmentations of the glycine conjugates obtained in the positive-ion mode were different from those in the negative-ion mode. Similar information on the substituents was obtained for the glycine conjugates.

The hydration structure of calcium nitrate tetrahydrate, Ca(NO3)2 · 4.1 H2O, melt at 328 K has been investigated by X-ray scattering and correlation method. Analysis of the radial distribution function and model fitting revealed that in the hydrate melt, a Ca2+ ion is surrounded by about six oxygen atoms, 4.1 of which come from water molecules at the average distance of 0.241 nm, 2.0 coming from the nitrate ions at the average distance of 0.254 nm. In the first coordination shell of the melt, the formation of a direct Ca2+-NO 3 − correlation, such as contact ion pairs, was suggested. The hydration structure of the melt analysed was compared with that of Ca(NO3)2 · 3.5H2O melt previously reported, and the decrease from nine of the reported melt to six in this melt was observed in the number of the nearest neighbour oxygen atoms around a Ca2+ ion. This implies that in the highly concentrated aqueous solution, the structure of the first coordination shell around the cation changes markedly with a small difference in the water molecule content.

溶融希土類塩化物の構造解析の二環としてDyCla単独浴およびDyCl3-NaCl等モル混合浴についてX線回折実験を行った。DyC13単独浴中には八面体型の錯陰イオン[DyCl6]3-が存在し,この錯イオンを構造単位とする二量体あるいは三量体などのクラスター状の多量体が存在する可能性を推測した。また,混合浴についても同様の検討を加えることにより単独浴との構造学的な差異,マクロな性質の相違など,溶融塩浴そのものに関する重要な情報が得られた。

Structural analyses of pure B2O3, B2O3(90 mol%)–Cs2O (10 mol%) and B2O3 (80 mol%)–Cs2O (20 mol%) glasses were made by an x‐ray diffraction method and the effects of Cs2O addition were investigated on the short range structure of the glasses. Furthermore, Raman spectroscopic studies were applied to analyze the interatomic interactions between boron and oxygen atoms. Due to x‐ray diffraction, pure B2O3 was confirmed to have BO3 triangles which formed the so‐called boroxol ring structure. When Cs2O was added to B2O3, the boroxol ring structure still remained but some parts of BO3 triangles was definitely converted to BO4 tetrahedra. This result was also supported by Raman spectroscopic observations. The other important consequences were that a Cs atom was surrounded by six O atoms, and four Cs–O interatomic distances were about 3 A but two pairs 3.5 A, indicating that the distorted Cs–O octahedra might exist in the B2O3–Cs2O glasses. This spatial arrangement of Cs and O atoms was quite different from the corresponding crystal structure in the standpoint of the enormous decrease in coordination number (the number of O atoms around a Cs atom).

The three-dimensional structures of molten alkali fluoroberyllates and alkaline earth silicates at the meta-composition have been analyzed by molecular dynamics simulation. A quantitative similarity was obtained between these two systems in respect of their partial distribution functions and the coordination numbers of their constituent ion pairs.