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Iguratimod (IGU), a disease-modifying antirheumatic drug launched in September 2012, has been reported to carry a risk of severe hemorrhages through a suspected interaction with warfarin (WF) in the all-case surveillance and early postmarketing-phase vigilance. To elucidate possible mechanisms of adverse interaction between IGU and WF, we analyzed the effects of IGU on the pharmacodynamics and pharmacokinetics of WF in rats. IGU was orally administered to male Wistar rats once daily for 5 d at 10 or 30 mg/kg in combination with WF at an oral dose of 0.25 mg/kg. Coadministration of IGU 30 mg/kg enhanced the anticoagulant activity of WF; prolonged blood coagulation time (prothrombin time and activated partial thromboplastin time) and decreased levels of vitamin K (VK)-dependent blood coagulation factors (II, VII, IX, and X) were observed. On the other hand, the pharmacokinetic parameters of WF including maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 to 24 h (AUC0-24 h) were not affected by the combination with IGU. IGU alone did not change blood coagulation time at doses up to 100 mg/kg, while VK-dependent blood coagulation factors decreased slightly at 30 and 100 mg/kg. These results suggest that the pharmacodynamic effect of IGU on VK-dependent blood coagulation factors is involved in the mechanism of drug-drug interaction of IGU with WF.

Orally administered Cd is predominantly distributed to the intestine, and the majority of this mucosal Cd is bound to metallothionein (MT). MT attenuates heavy metal-induced cytotoxicity by sequestering these metals and lowering their intracellular concentrations. In addition, MT acts as an extracellular transporter of orally administered Cd to the kidney. Because of its low molecular weight, the Cd-MT complex is freely filtered at the glomerulus, and the filtered Cd-MT is then incorporated into renal proximal tubular cells. Megalin, a multiligand endocytic receptor (also known as low-density lipoprotein receptor-related protein 2 or Lrp2), acts as the receptor for Cd-MT in a renal proximal tubular cell model. Here, we used the soluble form of 39-kDa receptor-associated protein (sRAP; also known as Lrpap1), a ligand of megalin, to inhibit megalin function, and then analyzed the effect of megalin loss on Cd-MT distribution and Cd-MT-induced nephrotoxicity in an animal model. Administration of sRAP to mice caused acute loss of megalin function by removing megalin in the brush border membrane. The pre-injection of sRAP decreased renal Cd content and decreased Cd-MT-induced kidney damage. Our results demonstrate that sRAP reduces Cd-MT-induced kidney toxicity in vivo.

Energy dispersive spectroscopic measurements of uranium ore were conducted using a superconducting phase transition-edge-thermosensor (TES) microcalorimeter mounted on a field-emission scanning electron microscope (SEM) to demonstrate its potential for high-precision microanalysis. The effective solid angle for X-ray detection is found to be larger than 2 msr by precise adjustments in the X-ray polycapillary alignment. The observed detection signal pulses with decay time constant of 50 μ s enable maximum count rates larger than 300 counts per second. The energy resolution was determined to be 14.6 eV FWHM at Al K α X-ray energies of 1487 eV. Distinct peaks appear in the resulting X-ra y energy spectrum associated with U ‐ M α , U ‐ M β and U ‐ M γ X-rays emitted by the uranium ore specimens. This spectrum includes weaker peaks corresponding to C ‐ K α , Fe ‐ L α , Cu-L and Sr L α 1 X rays.

Among viral vectors, the fiber-mutant adenovirus vector carrying the Arg-Gly-Asp (RGD) peptide sequence (Ad-RGD) seems to have potential for both clinical gene therapy and basic research. As a part of a thorough evaluation of Ad-RGD in preclinical studies, we designed an experiment to investigate in detail the distribution of Ad-RGD compared with conventional adenovirus vector (WT-Ad) in pregnant mice. Surprisingly, Ad-RGD had substantial placental tropism, at 10-100 times that of WT-Ad. Transgene expression was sustained for at least 7 days, and Ad-RGD expressing firefly luciferase or red fluorescent protein has so far caused no placental dysfunction leading to fetal death. Ad-RGD showed high levels of transduction efficiency in in vitro-differentiated trophoblast stem cells, in which higher expression of αvβ3 integrin than in undifferentiated cells was observed. Our results suggest that the use of Ad-RGD or another RGD-mediated targeting strategy holds promise for drug delivery to the placenta.

A transition edge sensor (TES) microcalorimeter has been developed for use as an energy dispersive X-ray spectrometer. The TES microcalorimeter is a thermal detector that enables one to determine the energy of an incident photon by measuring the resultant increase in temperature. In this work, a Ti/Au TES microcalorimeter was developed to measure LX rays emitted by transuranium elements. The phase transition temperature was set at ~200 mK by using a bilayer structure composed of a 110-nm-thick Au layer and a 40-nm-thick Ti layer. An Au of 5 µm thickness was deposited on the Ti/Au bilayer to achieve an absorption efficiency of 35-80 % for the energy range of LX rays (10-25 keV). The developed TES microcalorimeter was irradiated with LX rays emitted by an (241)Am source at an operating temperature of 140 mK. An energy resolution of ~80 eV (full width at the half maximum) was obtained for L(β1)X ray of 17.75 keV.

The principal 705 Japanese foods were selected from the Standard Tables of Food Composition in Japan — 2010 — (Standard Tables) because these foods are known to contain available carbohydrates including starch, glucose, fructose, sucrose maltose and/or lactose. Individual available carbohydrate contents were calculated and tabulated based both on the estimated saccharide (carbohydrate minus dietary fiber) content of each selected food in the Standard Tables and the starch and sugar content of the food included in The McCance and Widdowson’s The Composition of Foods, USDA National Nutrient Database for Standard Reference and other sources. Because the compiled tabulated form, the Japanese Starch and Sugars Presumptive Composition Tables (JSSPCT), is harmonized with the Standard Tables, one can utilize the data in the JSSPCT as a reference for research and other purposes until and after the Ministry of Education, Culture, Sports, Science and Technology or other national organization publishes the official tables for available carbohydrate composition of foods in Japan.

Renal biopsy paraffin sections were examined by low vacuum scanning electron microscopy (LVSEM) in the backscattered electron (BSE) mode, a novel method for rapid pathological analysis which allowed detailed and efficient three-dimensional observations of glomeruli. Renal samples that had been already diagnosed by light microscopy (LM) as exhibiting IgA nephropathy, minor glomerular abnormalities, and membranous glomerulonephritis (GN) were rapidly processed in the present study. Unstained paraffin sections of biopsy samples on glass slides were deparaffinized, stained with platinum blue (Pt-blue) or periodic acid silver-methenamine (PAM), and directly observed with a LVSEM. Overviews of whole sections and detailed observations of individual glomeruli were immediately performed at arbitrary magnifications between ×50 to ×18,000. Cut surface views and surface views of glomeruli were demonstrated at the same time. On Pt-blue-stained sections, podocytes, endothelia, mesangium, and glomerular basement membranes (GBMs) could be distinguished due to the different yields of BSE signals, and pathological features were investigated in every sample. The abnormal surface appearances of podocytes with foot processes and the varying thicknesses of GBM were revealed three-dimensionally, features difficult to observe under LM and transmission electron microscopy. PAM-positive GBM alterations in membranous GN were distinctly visualized through overlying cells without cell removal under LVSEM at high magnification. Not only prominent spike formation but also slight protrusions were clearly revealed in the side views of GBM. Crater-like or hole-like structures were shown in the en face views of GBM. Accordingly, LVSEM is expected to provide a novel approach to the pathological diagnosis of human glomerular diseases using conventional renal biopsy sections.

Ortho-para mixing interaction due to the coupling of nuclear and electron spins was detected for the first time by millimetre-wave spectroscopy of deuterated vinyl radicals, H2CCD and D2CCD, of which the ground states are split by the tunnelling motion of the α deuteron into two components 0+ and 0−, whose separations have been determined to be ΔE 0 = 1186.644(16) and 771.978(18) MHz, respectively. The observed tunnelling-rotation spectra are significantly perturbed by the ortho–para mixing interaction expressed by , where I β1 and I β2 are spins of the two hydrogen nuclei in the β position and S is the electron spin, which connects rotational levels in the 0+ and 0− states, one being an ortho level and the other a para level. The constants for H2CCD and D2CCD have been determined to be 68.06(53) and 10.63(94) MHz, respectively. The ortho and para states are mixed by about 0.097% and 0.0123% due to this interaction. The rate constant of para to ortho (I β = 0 → 1) conversion is predicted as 1.2 × 105 s−1 ...

The purpose of this paper is to demonstrate the powerful and flexible applicability of the Gram–Charlier expansion to pricing of a wide variety of interest rate related products involving interest rate risk and credit risk. In this paper, we develop easily implemented approximations of the prices of several derivatives; swaptions, CMS, CMS options, and vulnerable options. Associated with the default risk, a survival contingent forward measure is constructed.

A superconducting transition edge thermosensor (TES) microcalorimeter was irradiated with LX-ray photons emitted by an 241Am source maintained at an operating temperature of 120 mK using a compact liquid-helium-free 3He–4He dilution refrigerator directly coupled to a Gifford–McMahon (GM) cooler. The first and second stages of the GM cooler were directly coupled to the first and second pre-cool heat exchangers of a stick shaped dilution unit through copper plates in a vacuum chamber. The helium-free dilution refrigerator provided a cooling power of 20 μW at 100 mK. Detection signals of LX-ray photons emitted by the 241Am source were observed by operating the TES microcalorimeter in a severe noise environment induced by the mechanical vibrations of the GM cooler.

The amount of phenolic compound contained in the chestnut pellicle determines the degree of adhesiveness between the pellicle and kernel. The difficulty involved in pellicle removal in Japanese chestnut results from the accumulation of a large amount of phenolic compound in the pellicle. A new Japanese chestnut cultivar, ‘Porotan’, has a pellicle that is easily removed, like Chinese chestnut. In this study, the phenolic content of ‘Porotan’ pellicles was quantified and compared to those of Japanese (‘Kunimi’ and ‘Tsukuba’), Chinese (‘Houji 360’ and ‘Miyazakishinaguri’), and interspecific hybrid (‘Riheiguri’) chestnuts. Even though total phenolic content in ‘Porotan’ was highest among the cultivars measured, the ‘Porotan’ pellicle could be removed quickly. On the other hand, the phenolic content in a water-soluble extract, which shows the amount of phenolic compound accumulated on the inner surface of the pellicle, was low for ‘Porotan’ comparable to Chinese chestnut. Similar to total phenolic content, the phenolic content in an alcohol-soluble extract of ‘Porotan’, which shows the amount of phenolic compound accumulated in pellicle tissue, was highest among the cultivars. These results showed that the accumulation of phenolic compound on the inner surface of the ‘Porotan’ pellicle was low despite a large amount of phenolic compound in the pellicle tissue, and that the low accumulation of phenolics on the inner surface of the pellicle resulted in weak adhesion between the pellicle and kernel in ‘Porotan’.

The capability of an analysis system consisting of a low voltage scanning electron microscope, which is superior in spatial resolution and surface sensitivity, and a superconducting transition edge sensor (TES), which is under development, has been evaluated. The analysis system equipped with the TES, which has a superior energy resolution by about an order of magnitude to a conventional energy dispersive x-ray spectrometer (EDS), is useful for chemical state analysis that makes use of the strength ratio of characteristic x-rays of the same series. Elemental segregation in microstructures, whose size is several tens of nanometers as for simple energy-window maps or around 10 nm as for point analysis, is also detectable. It is expected that precise distribution of minor elements, which overlap with major elements in conventional EDS spectra, and chemical state maps of specific elements can be evaluated if the data processing of spectral imaging is incorporated into the system.

It has become a recent trend to apply a special environment into a lithography tool, for instance, immersion, EPL (Electron beam Projection Lithography) and EUVL (Extreme Ultra Violet Lithography) in order to exposure less than 22nm line and space at semiconductor industry field. For a cooling system that a heater is surrounded by metal can and a coolant is supplied into the can by using movable tubes, not only flexibility, damping, durability, particle protection and anti-liquid, etc, but also pressure-resistance, low outgasing and low leak from connections, etc might be strongly taken into account for vacuum lithography. Especially, because a coolant leak is very critical for EUVL in which a partial pressure of several molecular is strictly restricted, a special tube and joint have to be required in the case of liquid cooling system. On the other hand, a gas cooling can be one candidate because of a lower leak damage, however it is necessary to compensate its low cooling efficiency of gas system by using temperature feedback control. In this paper, two guide lines of a cooling mechanism for wafer and mask stage of vacuum compatible tool, a liquid cooling and gas cooling system are introduced.

The analytical performance of a scanning electron microscopy-energy dispersive spectroscopy (SEM–EDS) system equipped with a transition edge sensor (TES) microcalorimeter (µ-cal) in forensic analysis is examined. The TES microcalorimeter shows much better energy resolution than the conventional solid-state detector (SSD). We solved some identification problems caused by peak overlaps when forensic samples were analyzed by a conventional SEM-EDS system based on SSD. The microcalorimeter ED spectrum can reveal the coexistence of Ba and S in a paint layer of an automotive white paint fragment containing TiO2 as pigment and this may indicate the existence of BaSO4. The coexistence of K, Mg, Al, Si and Ti in the surface layer suggests the use of titanium dioxide (TiO2)-coated mica as a pearlescent pigment in paint. GSR particles are successfully discriminated by detecting Ba, Sb, Pb and S. An elemental mapping function of the TES microcalorimeter system was introduced for the first time and revealed the accumulation of Pb- and Sb-rich particles in GSR. These results suggest that the microcalorimeter SEM–EDS system offers analysis with both high-energy resolution and high-spatial resolution at low-excitation voltages. These advantages are fully utilized as powerful analytical tools in forensic laboratories. Copyright © 2009 John Wiley & Sons, Ltd.

We have developed a Transition Edge Sensor (TES) – Energy Dispersive Spectroscopy (EDS) for Transmission Electron Microscope (TEM) based on a dilution refrigerator. The dilution refrigerator was cooled by liquid helium (L-He), which was supplied from an L-He container separated from the dilution refrigerator. We adopted the hybrid magnetic shields combining a permalloy shield and a NbTi/Nb/Cu superconducting shield to operate the TEM–TES system under a magnetic field of 200 mT. The permalloy shield was used to prevent the ambient magnetic field until the NbTi superconducting shield cooled from room temperature (RT) to 2 K. The critical magnetic field was 220 mT for the TES change from a superconducting state to a normal state. The SQUID – current vs. bias current curve, under the condition that the snout was inserted in the TEM, was equal to the curve of the snout that was out of the TEM. The C (0 0 2) planes could be observed at 120 kV under the condition the snout was inserted in the TEM.

Suspended particulate matter (SPM) collected in the urban area of Tokyo was analyzed using a transition edge sensor (TES) microcalorimeter x-ray detector mounted on a FE-SEM system. This prototype microcalorimeter spectrometer with an energy resolution of 19 eV identified some severe peak overlaps in the spectra measured by the traditional Si(Li) solid state detector, including S Kα with Pb Mα, Zn Lα with Na Kα, and Ti Kα with Ba Lα. In addition, the TES microcalorimeter showed good spatial resolution for the microanalysis of SPM. The focused ion beam(FIB) was successfully applied to fabricate a cross section of a single SPM particle. The chemical compositonal difference between surface and inner parts, and among different surface parts of the SPM was also determined. Through combination of the FIB technique and the TES microcalorimeter, we achieved a better understanding of the SPM. Copyright © 2009 John Wiley & Sons, Ltd.

Accepted: 2009-08-04, 資料番号: SA1000816000

We consider a consistent pricing model of government bonds, interest-rate swaps and basis swaps in one currency within the no-arbitrage framework. To this end, we propose a three yield-curve model, one for discounting cash flows, one for calculating LIBOR deposit rates and one for calculating coupon rates of government bonds. The derivation of the yield curves from observed data is presented, and the option prices on a swap or a government bond are studied. A one-factor quadratic Gaussian model is proposed as a specific model, and is shown to provide a very good fit to the current Japanese low-interest-rate environment.

The Transition Edge Sensor (TES)-Energy Dispersive Spectrometer (EDS) is an X-ray detector with high-energy resolution (12.8eV). The TES can be mounted to a scanning electron microscope (SEM). The TES-EDS is based on a cryogen-free dilution refrigerator. The high-energy resolution enables analysis of the distribution of various elements in samples under low acceleration voltage (typically under 5keV) by using K-lines of light elements and M lines of heavy elements. For example, the energy of the arsenic L line differs from the magnesium K line by 28eV. When used to analyze the spore of the Pteris vittata L plant, the TES-EDS clearly reveals a different distribution of As and Mg in the micro region of the plant. The TES-EDS with SEM yields detailed information about the distribution of multi-elements in a sample.

At first, I explain some key points and difficulty of lithography tool design, issues that should be overcome during the development and requirements for stages in lithography tool in this paper. Then, I have ascertained a limit of static-pressure air bearing with differential pumping mechanism for vacuum application, for instance EUVL(Extreme Ultra Violet Lithography tool) by manufacturing so-called the “vacuum compatible” 1-axis air bearing and verifying the performance by comparing with equivalent model simulation. Finally, one of MAGLEV(MAGnetic LEVitated) stage concepts is proposed instead of common AIRLEV(AIR LEVitated) stage by seriously considering a high throughput for mass production. I simultaneously contribute 2nd paper, “Development of 6DOF Magnetic Levitation Stage for Lithography Tool -Proof Of Concept (Second Report)-“ which is a sequel to this paper.

The present study introduces a novel method for the direct observation of histological paraffin sections by low vacuum scanning electron microscopy (LVSEM) with platinum blue (Pt-blue) treatment. Pt-blue was applied not only as a backscattered electron (BSE) signal enhancer but also as a histologically specific stain. In this method, paraffin sections of the rat tongue prepared for conventional light microscopy (LM) were stained on glass slides with a Pt-blue staining solution (pH 9) and observed in a LVSEM using BSE detector. Under LVSEM, overviews of whole sections as well as three-dimensional detailed observations of individual cells and tissues could be easily made at magnifications from x40 to x10,000. Each kind of cell and tissue observed in the section could be clearly distinguished due to the different yields of BSE signals, which depended on the surface structures and different affinities to Pt-blue. Thus, we roughly classified cellular and tissue components into three groups according to the staining intensity of Pt-blue observed by LM and LVSEM: 1) a strongly stained (deep blue by LM and brightest by LVSEM) group which included epithelial tissue, endothelium and mast cells; 2) a moderately stained (light blue and bright) group which included muscular tissue and nervous tissue; 3) an unstained or weakly stained (colorless and dark) group which included elastic fibers and collagen fibers. We expect that this method will prove useful for the three-dimensional direct observation of histological paraffin sections of various tissues by LVSEM with higher resolutions than LM.

Cytosolic zinc-binding protein, metallothionein (MT), is normally saturated with Zn. It is thought that Zn-saturated MT (Zn-MT) acts as a major intracellular Zn pool. Metal-response element-binding transcription factor-1 (MTF-1) plays an important role in Zn-mediated MT transcription. Here, we showed that degradation of Zn-MT activates MTF-1. We measured activated MTF-1 using an electrophoretic mobility shift assay. Interleukin-6 induced MT expression and increased MTF-1 activity. MTF-1 activation was not observed in MT-overexpressing cells. MT-dependent MTF-1 activation was observed only after treating MT-overexpressing cells with cycloheximide (CHX), a protein synthesis inhibitor. CHX-treatment increased the degradation/synthesis ratio of protein. An increase in the degradation/synthesis ratio for the MT protein is expected to increase the level of labile Zn and activate MTF-1. Recombinant MTF-1 was activated by H2O2 only in the presence of Zn-MT. Oxidative stress activated MTF-1 DNA-binding activity in primary cultured hepatocytes but not in MT-deficient hepatocytes. These findings suggest that degradation of Zn-MT activates MTF-1, and that MT plays an important role in zinc-mediated signal transduction.

We have constructed a new system of narrow gap infrared reflection absorption spectroscopy (NG-IRRAS) for solid–solution interface biomaterials. A sample solution is confined in a narrow space between the CaF2 prism and the substrate surface. The sample holder is specially designed to keep the narrow space constant during the measurement process. Absorption spectra of the solution phase immunoglobulin G (IgG) and the solid–solution interface IgG covalently bonded to the carboxyl-terminated self-assembled monolayer on the gold surface have been clearly observed with good reproducibility. Noticeable molecular conformation change induced by adsorption was not observed.

Variations in conjugated linoleic acid (CLA) concentrations in Holstein dairy cows milk, depending on feeding systems in different seasons was investigated. Milk samples were collected from Holstein dairy cows, which either grazed for whole days (WG), only daylight hours (TG), or were offered a total mixed ration (TMR) and experienced no grazing (NG), from April to December of 2005. In April, November and December, the cows in TG and WG treatments received grass silage and some concentrate, while from May to October, the cows grazed on temperate pasture. The cows in NG treatment received the TMR throughout the season. The major fatty acid obtained in the pastures was linolenic acid. There was no significant difference in the pasture's linolenic acid concentrations from May to September, but there was a significant decrease in October. However, the linolenic acid concentrations obtained in the pasture were always much higher than those obtained from the TMR. Linoleic acid was also the major fatty acid in the TMR, but these concentrations were higher in the TMR than in the pasture. There was no significant difference in milk cis9trans11CLA (c9t11CLA) concentrations between the three feeding systems while the cows were fed on conserved pasture in April, November and December. Although c9t11CLA concentrations were lower in the TMR, it was found that the cows which grazed in fresh pasture experienced significantly higher concentrations of c9t11CLA in their milk than those which received only TMR. It was also found that cows in the WG treatment experienced higher c9t11CLA concentrations than those in the TG treatment. In the WG and TG treatments, c9t11CLA concentrations were highest in June, after which, they gradually decreased (p 0.05) with season. Overall, trans11C18:1 and c9t11CLA were greatly influenced by season, with higher variation in the WG treatment than in the TG treatment and no variation in the NG treatment. (Key Words : Feeding System, Seasonal Change, Conjugated Linoleic Acid, Milk Fatty Acids Composition)

Microwave spectrum of the GeCl radical in the ground vibronic state was observed for the 2 Π 1/2 as well as 2 Π 3/2 spin substate. The GeCl radical was generated in a free-space absorption cell by a dc discharge in GeCl 4 diluted with Ar. The observed spectra were subjected to a least-squares analysis to yield accurate molecular constants; those of the most abundant isotopomer 74 Ge 35 Cl are as follows; B 0 = 4535.91396(70) MHz, D 0 = 2.5413(13) kHz, A D 0 = 4.87595(37) MHz, ∣ p 0 ∣ = 17.87(31) MHz, ∣ q 0 ∣ = 4.06(18) MHz, and ∣ p 0 + 2 q 0 ∣ = 25.984(39) MHz, where uncertainties given in parentheses correspond to one standard deviation. The absolute signs of p 0 and q 0 are indeterminable, although they have the same sign. The equilibrium rotational constant B e and the vibration–rotation interaction constant α e were derived by analyzing the mass dependence of the B 0 constants for seven isotopomers. The equilibrium bond length was determined to be r e = 2.163739(23) A.

Essential metals (EMs) can affect the metabolism of nonessential metals. It has been suggested that Fe deficiency increases intestinal absorption of Cd via divalent metal transporter 1 (DMT1). To investigate whether EM nutritional status is a host risk factor for Cd accumulation, we studied the effect of nutritional status of Ca, Cu, Mg, Zn, and Fe that most often ingested by humans at levels below recommended dietary allowances on tissue accumulation of orally administered Cd. Mice were divided into groups and given different EM-deficient (EMDF) diets (CaDF, CuDF, MgDF, ZnDF, or FeDF) for 4 weeks. EMDF mice had significantly (p < 0.05) lower plasma or hepatic concentrations of the deficient EM than did mice receiving control diets. Hepatic Cd accumulation was significantly (p < 0.05) increased after oral Cd administration in all EMDF mice, but not in any EM-supplemented mice. Intestinal expression of mRNAs for the Fe-transporters DMT1 and ferroportin was increased in FeDF mice, but not in other EMDF mice, causing an increase in hepatic Fe concentration. Similarly, intestinal expression of mRNA for calcium transporter 1 was significantly increased in CaDF mice, but not in other EMDF mice. These results suggest that DMT1 is not the sole transporter of Cd, and that Cd is absorbed and accumulated through multiple pathways that maintain EM homeostasis in EMDF condition. Therefore, EM nutritional status is a risk factor for increasing hepatic accumulation of ingested Cd.

A prototype transition-edge sensor (TES) microcalorimeter is successfully integrated into a commercial field-emission scanning electron microscope (FE-SEM). The microcalorimeter is composed of a gold (Au) absorber, a Au/Ti bilayer thermometer and a thermal isolation structure with a SiNx membrane. Operating temperatures of 100–150 mK are obtained with a dilution refrigerator. The measured energy resolution was between 19–22 eV for Al Kα at an acceleration voltage of 5 keV. The newly developed system was applied to the analysis of nanosheets for the first time at a low acceleration voltage (≤ 5 kV). The energy dispersive spectrometer (EDS) spectra of Nb3O8 nanosheets of different thicknesses (less than 20 nm) were successfully detected. Moreover, Au particles on carbon nanotubes with a thickness less than 1 nm are detected clearly. With further improvement of both energy resolution and count rate, this system holds the promise for practical X-ray compositional characterization of nanomaterials with high image spatial resolution in the low-acceleration-voltage regime.

Abnormal iron (Fe) metabolism induces iron-deficiency anemia (FeDA) and also affects body cadmium (Cd) accumulation. However, whether hemolytic anemia also affects Cd metabolism is not known. We compared the intestinal absorption and tissue accumulation of Cd after oral administration of Cd to mice with hemolytic anemia induced by treatment with phenylhydrazine (PHA mice) to that in mice with FeDA. Although the hematocrit decreased significantly in mice with either type of anemia, the Fe concentration decreased in the livers and kidneys of FeDA mice, but increased in those of PHA mice. After an oral administration with various amounts of Cd, hepatic and renal Cd concentrations significantly increased in both FeDA and PHA mice. An intraduodenal injection of Fe raised the hepatic Fe content in FeDA mice to the control level and raised the hepatic Fe content in PHA mice to 2.4 times that in control mice. Intestinal divalent metal transporter 1 (DMT1) expression increased significantly in mice with both types of anemia. These data indicate that, despite the accumulation of hepatic Fe associated with PHA, PHA also significantly increases hepatic and renal Cd accumulation according to an stimulation of intestinal DMT1 expression, as occurs in FeDA mice. This suggests that anemia may be a risk factor for Cd accumulation.

A microcalorimeter with the superconducting transition edge sensor (TES) with a Au absorber of 5.0 μm thick was fabricated for the energy dispersive measurement of LX-ray photons emitted from transuranium elements. The TES microcalorimeter and a superconducting quantum interference device (SQUID) amplifier chips were cooled by operating a compact 3He-4He dilution refrigerator without consuming liquid helium by loading a Gifford-McMahon (GM) cooler. Since the cold stages of the GM cooler are tightly coupled to the heat exchangers of the dilution refrigerator, the TES and SQUID chips suffered from mechanical vibrations induced by a reciprocating motion of the displacer of the GM cooler. Detection signals of LX-ray photons emitted from an 241Am source were observed by operating the TES microcalorimeter in severe noise environment induced by mechanical vibrations.

Infrared spectrum of the cobalt carbonyl radical CoCO produced by the 193 nm excimer laser photolysis of cobalt tricarbonyl nitrosyl Co(CO) 3 NO was observed by time-resolved diode laser spectroscopy. More than 600 lines were identified as belonging to the ν 1 (C–O stretch) fundamental band, consisting of the Ω = 5 / 2 and 3/2 subbands, and the associated hot bands 1 1 2 , 1 0 1 2 1 1 , 1 0 1 3 1 1 , and 1 0 1 2 2 2 . The 2 Δ i electronic ground state of CoCO was experimentally confirmed. The ν 1 band origins are 1974.172582(93) cm −1 and 1973.53178(14) cm −1 for the Ω = 5 / 2 and 3/2 subbands, respectively. The rotational constant in the ground state was determined as B 0 = 4427.146 ( 50 ) MHz. The centrifugal distortion constant D 0 = 1.1243 ( 68 ) kHz was obtained for the Ω = 5 / 2 substate of the ground state. The equilibrium rotational constant B e = 4435.44 ( 14 ) MHz was derived, together with the vibration–rotation interaction constants.

Essential metals can affect the metabolism of nonessential metals. Calcium (Ca) is an essential mineral that is commonly lacking in the diet. When we fed 5-week-old male mice for 4 weeks on a purified diet containing 0.005% Ca (CaDF mice), the Ca concentration in the plasma, liver and kidneys did not decreased. Cd accumulation increased in the liver and kidneys of CaDF mice given 1 mg/kg Cd orally each day for 5 days, but not in those given intraperitoneal injections of Cd or Cd-metallothionein (Cd-MT). The zinc (Zn) concentration increased significantly in the intestinal cytosol and plasma during the time the mice were fed the low-Ca diet, and expression of both MT-1 and ZnT-1 sharply increased with a similar time course. Intestinal mRNA expression of CaT1, a Ca transporter, was more than 10 times higher in CaDF mice than in controls, although expression of other transporters, including DMT1, decreased in CaDF mice. These results suggest that CaT1 may stimulate the intestinal absorption of Cd and Zn, and some Cd may be distributed to the kidneys along with MT induced by Zn.

We have calculated the three-dimensional potential energy surfaces for the 1 2A′ and 1 2A″ states of BrCN+ at the MR-SDCI_DK+Q/[QZP-ANO-RCC (Br, C, N)] level of theory, where MR-SDCI_DK means ‘multi-reference single and double excitation configuration interaction calculation with Douglas–Kroll Hamiltonian.’ These ab initio potential energy surfaces have a common minimum (corresponding to the X ˜ 2 Π state) at a linear equilibrium structure with re(Br–C) = 1.735 A and re(C–N) = 1.199 A. Variational RENNER calculations yield a zero-point averaged structure (with the structural parameters calculated as expectation values over rovibrational wavefunctions) with 〈r(Br–C)〉0 = 1.739 A, 〈r(C–N)〉0 = 1.204 A, and 〈∠(Br–C–N)〉0 = 172(4)°. A severe Fermi resonance between 2ν2 and ν3 has been found theoretically for the 2A″ potential energy surface. Comparing the ab initio zero-point averaged structure with a recent, experimentally derived r0 structure, it is concluded that the effects of large-amplitude bending motion should be taken into account explicitly in the process of deriving the r0 structure from the experimental values of the rotational constants. The electronic structure of X ˜ 2 Π BrCN+ has also been discussed.

We previously demonstrated that activation of sensory neurons increases endothelial prostaglandin I 2 (PGI 2 ) production by releasing calcitonin gene-related peptide (CGRP). Since PGI 2 reduces post-traumatic spinal cord injury (SCI) by inhibiting tumor necrosis factor (TNF) production, activation of sensory neurons in the spinal cord tissue may ameliorate spinal cord injury. This study examines these possibilities using rat models of compression trauma-induced SCI. Both SB366791, a specific vanilloid receptor antagonist, and CGRP (8-37), a CGRP receptor antagonist, significantly inhibited trauma-induced increases in spinal cord tissue 6-keto-PGF 1α levels. SB366791, CGRP (8-37) and indomethacin (IM) enhanced increases in spinal cord tissue TNF levels at 2 h after trauma and exacerbated motor disturbances. Administration of CGRP significantly reduced motor disturbances and inhibited increases in spinal cord tissue TNF levels through enhancement of increases in tissue levels of 6-keto-PGF 1α . These observations strongly suggest that activation of sensory neurons might ameliorate compression trauma-induced SCI, inhibiting TNF production through enhancement of endothelial PGI 2 production. Thus, although the spinal cord sensory neurons function as nociceptive neurons, they could also be critically involved in the cytoprotective system that attenuates SCI development and, thus, pharmacological stimulation of spinal cord sensory neurons might contribute to reduce spinal cord injury.

This paper introduces an aqueous solution of platinum blue (Pt-blue) as an alternative to uranyl acetate (UA) for staining in transmission electron microscopy (TEM). Pt-blue was prepared from a reaction of cis-dichlorodiamine-platinum (II) (cis-platin) with thymidine. When Pt-blue was dried on a microgrid and observed by TEM it showed a uniform appearance with tiny particles less than 1 nm in diameter. The effect of Pt-blue as an electron stain was then examined not only for positive staining of conventional ultrathin resin sections and counterstaining of post-embedding immuno-electron microscopy but also for negative staining. In ultrathin sections of the rat liver and renal glomerulus, Pt-blue provided good contrast images, especially in double staining combined with a lead stain (Pb). Almost all cell organelles were clearly observed with high contrast in these sections. Glycogen granules in the hepatic parenchymal cells were particularly electron dense in Pt-blue stained sections compared with those treated with UA. In longitudinal and transverse sections of budding influenza A viruses, a specific arrangement of rod-like structures, which correspond to the ribonucleoprotein complexes, was clearly shown in each virion stained with Pt-blue and Pb. When post-embedding immunoelectron microscopy was performed in ultrathin sections of HeLa cells embedded in Lowicryl K4M, the localization of Ki-67 protein was sufficiently detected even after Pt-blue and Pb staining. The present study also revealed that Pt-blue could be used for the negative staining of E. coli, allowing the visualization of a flagellum. These findings indicate that Pt-blue is a useful, safe, and easily obtainable electron stain that is an alternative to UA for TEM preparations.

Sadatomi and Kawahara invented a multi-fluids mixer which is categorized as a twin-fluid type but have a merit of water suction type. The mixer is usable to generate micro- bubbles, etc. besides mists, fine droplets. In the mists generation, pressurized air alone is supplied because water can be sucked automatically by a negative pressure arisen downstream from the orifice in the mixer. The objective of the present study is to compare the performance between the above twin-fluid type atomizer and a common single-fluid swirl type atomizer studied in the present experiments. The comparison results showed that the twin-fluid type was superior to the singe-swirl type in the performance of CO2 adsorption by the mists. The CO2 adsorption rate by the twin-fluid type was about twice. Such results on the experiments and the comparisons are described in this paper. Keywords—atomizer, twin- and single-fluid types, hydraulic performance, CO2 adsorption

Iguratimod (IGU), a small-molecule compound, was developed as a disease-modifying antirheumatic drug in Japan. The pharmacological studies showed that inhibition of the production of cytokines and immunoglobulins mainly contributes to its improvement effect on animal arthritis models. The first clinical study of IGU in Japanese patients with rheumatoid arthritis was started in 1992 and Phase III studies were started in 1998. From the results of Phase II studies, a dose-escalating regimen was recommended to relieve the side effects. In a double-blind study comparing the efficacy and safety of the drug with those of placebo and salazosulfapyridine, it was confirmed that IGU was superior to placebo and was not inferior to salazosulfapyridine. Furthermore, a double-blind controlled trial of IGU in combination with methotrexate revealed an efficacious and manageable safety profile. IGU would be widely used as a new option for rheumatoid arthritis treatment and combination drug with methotrexate.

crews become more sophisticated. A marked increase in the recent volume of emergency calls is another issue of concern. Currently, private services for transportation of non-acute or minor injury/illness have been introduced in some areas, and dispatch protocols to triage 199 calls are in development., Emergency medical services are provided by the fire defense headquarter of the local government in Japan. We have a one-tiered EMS system. The ambulance is staffed by three crews trained in rescue, stabilization, transportation, and advanced care of traumatic and medical emergencies. There are three levels of care provided by ambulance personnel including a basic-level ambulance crew (First Aid Class one, FAC-1), a second level (Standard First Aid Class, SFAC), and the highest level (Emergency Life Saving Technician, ELST). ELSTs are trained in all aspects of BLS and part of ALS procedures relevant to prehospital emergency care. Further development of an effective medical control system is imperative as the activities of ambulance

The genomic DNA of crucian carp (Carassius cuvieri) metallothionein-II (ccMT-II), with its upstream region, was obtained. The sequence analysis of its upstream region revealed several putative cis-acting elements including seven metal regulatory elements (MREs), three activator protein 1 (AP1), two glucocorticoid response elements (GREs), etc. The seven MREs locate into two clusters, a distal cluster with four MREs within -800/-600bp from the translation start site and a proximal cluster with three MREs close to TATA box. In transient luciferase gene expression assays, both of the distal and proximal cluster MREs have significantly shown synergistic effects in the transcription of ccMT-II gene; the proximal cluster of MREs serves as the major elements in metal inducing activity; Zn(2+) and Cd(2+) served as much stronger inducers than Cu(2+) shown in ccMT-II expression. The two GRE homologous sequences in ccMT-II promoter showed not to be inductive in either HepG2 or HEK293.

The effectiveness of two inducible nitric oxide synthase (iNOS) inhibitors on allergic airway inflammation was investigated under different administration schedules. Rats sensitized to ovalbumin (OVA) were exposed to OVA for 3 consecutive days. Both iNOS inhibitors showed markedly different effects between two pretreatment schedules: pretreatment before each of three OVA exposures (S1) and before the third exposure alone (S2). S1 pretreatment resulted in higher pulmonary resistance than triple OVA alone. This potentiation was associated with increased eosinophil infiltration and malondialdehyde levels in the lungs, which were suppressed by superoxide dismutases (SODs) but not by methylprednisolone. However, the S2 administration of both iNOS inhibitors completely suppressed the airway response. Administration by schedule S1 completely suppressed plasma nitrite and nitrate levels, but that by S2 caused only a slight suppression. The triple OVA exposures resulted in the upregulation of iNOS in alveolar macrophages and arginase activity, Mn- and Cu/Zn-SOD expression, and nitrotyrosine and lipid peroxide deposition in the airway. However, inhibitors administered by schedule S1 suppressed this upregulation, but further potentiated nitrotyrosine, which in turn was inhibited by SOD. Although iNOS inhibitors may be beneficial for asthma, repeated administration may be detrimental because of extensive reduction of NO and downregulation of SOD.

The authors examined whether a serum pepsinogen test (SPT) based on the combination of the serum pepsinogen I level and pepsinogen I/II ratio is a good predictor of gastric cancer occurrence in a general Japanese population. A total of 2,446 subjects aged � 40 years were classified into negative, positive, and strong-positive SPT groups and were followed prospectively for 14 years (1988–2002). Compared with that for the negative SPT group (26 men, 10 women), gastric cancer incidence increased significantly for both men (n ¼ 17; age-adjusted hazard ratio ¼ 4.56, 95% confidence interval: 2.42, 8.60) and women (n ¼ 6; age-adjusted hazard ratio ¼ 5.84, 95% confidence interval: 2.00, 17.11) in the strong-positive SPT group. It was also significantly higher in the positive SPT group for men (n ¼ 23; age-adjusted hazard ratio ¼ 3.91, 95% confidence interval: 2.23, 6.86). These associations did not attenuate even after adjustment for other comprehensive risk factors. Stratified analysis revealed significant associations between the SPT and development of intestinal-type gastric cancer as well as of cancer in both Helicobacter pylori–negative and –positive subjects. These findings suggest that the SPT can serve as a predictor of intestinal-type gastric cancer, irrespective of H. pylori infection. cohort studies; gastritis, atrophic; Helicobacter pylori; pepsinogens; stomach neoplasms