We have been working on the development of a full Eulerian formulation method for solving fluid-structure interaction problems.The original method [1] has been extended for fluid-membrane interaction problems [2].This method is applied to the blood flows containing red blood cells and platelets.Then,it is further extended to multiscale thrombosis simulation,which couples Monte-Carlo simulations for the molecular scale protein-protein interactions with continuum scale simulations.These simulators are developed for the massively parallel computation.The results reveal that the flow fluctuation given by the presence of red blood cells plays an important role to make the platelets adhering on the vessel wall.

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SPH simulation is a meshless Lagrangian technique which is appealing as a possible alternative to Numeric techniques currently used to analyze complicated structures,fracture of materials and high deformation events.In the present study,the SPH algorithm has been developed to elasto-plastic analysis and fracture analysis in the field of solid dynamics.In this study data generation technique for large scale structures has been also developed.The accuracy of SPH method is important when the method is used for industrial design of structures.It is cleared that the accuracy of SPH method is basically 2nd order and the results have sufficient accuracy comparing with the results of standard FEM code(LS-dyna).SPH method is suite for computing fracture of solid materials because of the meshless algorithm and successfully applicable to crackpropagation problems of practical use.

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山形県，新潟県及び秋田県で発生した Karp 型感染によるつつが虫病患者由来 Orientia tsutsugamushi 遺伝子の亜型分類を行った．30 人の患者血液から抽出された DNA を試料とし，nested-PCR で得られた O. tsutsugamushi の 56-kDa タンパク遺伝子のダイレクトシークエンスを行い，その解析を行った．30 例を解析した結果 27 例と 3 例の 2 つのグループに分類された．データベース株と比較したところ 27 例のグループはJ P-1 型に分類されるyeo-joo 株と，3 例のグループは JP-2 型に分類される CMM1，KNP1 及び KNP2 株とシークエンスが一致した．また，分子系統樹においてもそれぞれがクラスターを形成し，27 例のグループは

- 型，3 例のグループは JP-2 型に分類されると判断された．わが国では，JP-2 型が主流と考えられてきたが，この地域では - 型が主流である可能性がある．今後，この株を分離し精査する必要がある．

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The tsunami caused by the great East Japan earthquake gave serious damage in the coastal areas of the Tohoku district.Numerical simulation is used for damage prediction as disaster measures to these tsunami hazards.Generally in the numerical simulation about the tsunami propagation to the coast from an open sea,shallow-water equations are used.This research focuses on viscous shallow-water equations and attempts to generate a computational method using finite element techniques based on the previous investigations of Kanayama and Ohtsuka(1978).First,the viscous shallow-water equation system is derived from the Navier-Stokes equations,based on the assumption of hydrostatic pressure in the direction of gravity.Next the numerical scheme is shown.Finally,tsunami simulation of Hakata bay is shown using the approach.

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In this research,an optimization methodology is proposed for the piezoelectric transducer layout and length of energy-recycling type semi-active vibration control system for a space structure.The design variables are set as the length of the piezoelectric actuator on each truss element.Physical properties of the actuator are formulated as the function of the design variables.The vibration analysis problem of the truss structure is formulated based on the transient response analysis using the modal method.The objective function is set as the integration of the square of all displacement over the whole analysis time domain.The sensitivity of the objective function is derived based on the adjoint variable method.Based on these formulations,an optimization algorithm is constructed using the method of moving asymptotes(MMA).Numerical examples are provided to illustrate the validity and utility of the proposed methodology.

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Close physical association of Ca_V1.1 L-type calcium channels (LTCCs) at the sarcolemmal junctional membrane (JM) with ryanodine receptors of the sarcoplasmic reticulum (SR) is crucial for excitation-contraction coupling (ECC) in skeletal muscle. However, molecular mechanism underlying the JM-targeting of LTCCs is unexplored. Junctophilins (JPs) are a molecule known to stabilize the JM complex by bridging the sarcolemma and SR membranes. Here we examined whether JPs contribute to the JM-targeting and proper function of LTCC. We first suppressed JPs by siRNA in cultured myotubes. Suppression of JPs disturbed the JM-targeting of LTCC and a robust calcium transient in response to electrical stimulation. Co-immunoprecipitation and GST pull down assays demonstrated that JPs physically interacted with 12 amino acid residues in proximal C-terminus of the Ca_V1.1. We prepared and transfected a

mutant lacking the C-terminal transmembrane domain (ΔTM) into cultured myotubes. ΔTM was not specifically clustered to JM but diffusely localized over the entire plasma membrane in the myotubes. Transient expression of ΔTM inhibited the JM-targeting of Ca_V1.1, indicating a dominant negative effect of the mutant. To examine the in vivo effect of , ΔTM was transduced in the flexor digitorum profundus (FDB) or tibialis anterior (TA) muscle of living mice by using an adeno-associated virus (AAV)-mediated gene delivery system. Ca²⁺ imaging assay in the FDB fibers showed that expression of ΔTM significant decreased the peak amplitude of calcium transients elicited by electrical stimulations. Significant change in SR Ca²⁺ content was not observed between control and ΔTM -expressed FDB fibers. Immunocytochemical analysis revealed that ΔTM was localized more strongly to the sarcolemmal than the T-tubule membrane. Interestingly, abundant Ca_V1.1 signals were observed in the sarcolemma of ΔTM -expressing fibers but not control fibers. The proximity ligation assay revealed that the physical coupling between LTCC and RyR in the FDB fibers was significantly decreased by ΔTM. Moreover, the specific force of the TA muscle was dramatically reduced compared to the control. From these results, we conclude that the physical interaction between JPs and the C-terminus of Ca_V1.1 is crucial for the excitation-contraction coupling of the skeletal muscle.

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All platinum group element (PGE) abundances of a standard rock - are determined by isotope dilution method (for Ru, Pd, Os, Ir and Pt) and external calibration method (only for Rh) using ICP-MS combined with a fire assay preconcentration technique. The errors range 13–25% (2σ; n = 5), which are comparable with those by the similar methods combined with chemical separation of PGE (Pearson and Woodland, 2000; Meisel et al., 2001). Large deviations between our data and preferable values proposed by the Geological Survey of Japan (GSJ) are observed for Os and Ir. The scattered Os data might be indicative of heterogeneity of Os in -. From various viewpoints, it seems likely that our Ir data are much more reliable than the preferable values proposed by GSJ.

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EBRANTIL^® Capsules are a drug product of urapidil, an alpha-1 adrenergic receptor antagonist, in the form of enteric/sustained-release granule filled capsules. This product can be administered as a solution prepared by the simple suspension method (SSM) to patients with gastrostomy through tubes; however, there is no information on the elution behavior of the drug administered by SSM.

In this study, one EBRANTIL^® Capsules 15 mg was put in 20 mL of purified water or Japanese Pharmacopoeia (

) st fluid for the dissolution test (pH 1.2) of 55 and 37℃. The test container was left for 10 minutes, then the content was suspended. The dissolution test was carried out in st fluid.

The elution of urapidil from EBRANTIL^® Capsules untreated by SSM was 30% or less in 60 minutes. Ninety percent or greater of urapidil eluted in 30 minutes treated with water of 55℃. The elution rate of urapidil treated with water of 37℃ was relatively slower than that; however, 60% or greater urapidil eluted in 60 minutes. The elution behavior of urapidil from the capsule treated with

st fluid was almost the same as that of the untreated EBRANTIL^® Capsules. These data suggest that the granules in the capsules were slightly dissolved in st fluid, but they dissolved immediately in water of 55 and 37℃.

In conclusion, EBRANTIL^® Capsules should not be administered by SSM to avoid lowering blood pressure when treating patients.

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Osmium and Reabundance and ¹⁸⁷Os/¹⁸⁸Os ratios of reference rocks, JB-1a, JA-2 and -, were determined through isotope dilution—negative thermal ionization mass spectrometry (ID-NTI-MS). Duplicate analyses of each sample show heterogeneous distribution of Re and Os in the reference rocks. The ranges of Re and Os concentrations are 150–200 and 9–12 ppt for JB-1a, 59–67 and 10–12 ppt for JA-2 and 28–32 and 2400–2700 ppt for -, respectively. Extremely high ¹⁸⁷Os/¹⁸⁸Os ratios of 0.20–0.28, much higher than that of the chondritic mantle (0.12–0.13), of JB-1a and JA-2 indicates involvement of components with highly radiogenic ¹⁸⁷Os/¹⁸⁸Os ratios such as the subducting slab-derived materials. The reference rocks -, Horoman peridotite, yields sub-chondritic Os isotopic composition of 0.12.

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機器中性子放射化分析(INAA)により,地質調査所(GSJ)において作製されたたい積岩試料のJLk-1(湖底たい積物),JLs-1(石灰岩),JDo-1(ドロマイト)と火成岩試料の-(ダナイト)の4種類の標準岩石試料中の微量元素を多元素同時定量する方法を検討した.照射は通常のフィルターなし照射とカドミウムフィルター照射の2種類の方法で武蔵工大炉(MITRR)で行った.測定はGe検出器によるγ線スペクトロメトリーの外にGe検出器とNaI(Tl)検出器とを組み合わせた反同時測定によるγ線スペクトロメトリー及びGe検出器とエネルギー範囲を限定したNal(Tl)検出器との同時測定によるγ線スペクトロメトリーも用いた.52元素の定量を試みてJLk-1で44元素,JLs-1で32元素,JDo-1で35元素及び-で24元素が定量できた.

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  There are various opinions regarding the different functions of original and generic drugs. We used the paddle method to perform dissolution tests on pravastatin sodium tablets (10 mg) to investigate the causes for these differences. We used water and buffer solutions adjusted to pH 1.2 () and pH 6.8 (JP2), which are described in the Japanese Pharmacopoeia. The pravastatin concentration was measured by UV spectroscopy and HPLC. There were significant differences in the percentages dissolved of original and generic drugs after 5 and 10 min. On the other hand, the dissolution behaviors using water and JP2 measured by HPLC were similar to the results obtained by UV spectroscopy. However, the percentage dissolved of pravastatin using decreased with time because pravastatin degraded in . There were also significant differences in the pravastatin concentrations of the original and generic drugs at 5, 15, 30, and 45 min. Based on the above results, since the original drug has a slower dissolution rate than the generic drugs, it is necessary to be cautious about the degradation of pravastatin in the stomach and the bioavailability of pravastatin due to the different dissolution rates and the different residual amount of pravastatin in the stomach.

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A solution containing xanthan gum (XTG), a thickening polysaccharide, as a main ingredient is used in taking medicines to prevent aspiration in patients with difficulty swallowing. Recently, there have been reports of XTG thickening solution (XTG-SOL) causing delays in the disintegration and dissolution of uncoated tablets and hindering the medicinal effects. However, studies on film-coated tablets have not yet been conducted. Since the film coating of tablets prevents direct contact with the thickening solution, we investigated whether film coating reduces delays in disintegration and dissolution of tablets.

Tablets were first immersed in XTG-SOL for 1 minute and then subjected to disintegration and dissolution tests. Disintegration tests on water-soluble coated placebo tablets were conducted in the first Japanese Pharmacopoeia solution (

, pH 1.2), and the results were compared with those of uncoated tablets and orally disintegrating (OD) tablets. Likewise, commercially available OD tablets containing film-coated multi-particulates, uncoated tablets, and OD tablets were also subjected to identical tests in . For enteric-coated tablets, a disintegration test was conducted in and JP2 (pH 6.8).

Compared with the uncoated and OD placebo tablets, the film-coated tablets immersed in XTG-SOL showed the shortest delay in disintegration. Although a delay in the disintegration time was observed for the OD tablets containing film-coated multi-particulates, no delay in the dissolution rate or profile of the active ingredient was evident. XTG-SOL showed no effect on disintegration of the enteric-coated tablets, indicating no influence on the enteric property. These results demonstrate that film-coated tablets appear unaffected by immersion in XTG-SOL.

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Functional coupling between L-type calcium channels (LTCCs) of the sarcolemma and ryanodine receptors (RyR) of the sarcoplasmic reticulum (SR) at the junctional membrane (JM) is crucial for the excitation–contraction coupling (ECC) of striated muscles. Junctophilins (JPs) stabilize the JM by bridging the sarcolemmal and SR membranes. We recently reported that expression of

mutant lacking its C-terminal transmembrane domain in mouse skeletal muscles significantly reduced their contractile force without disrupting JM, revealing a novel role of to directly support the physical LTCC–RyR1 interaction. Thus, we next investigated by using an analogous JP2 mutant (JP2Δ427), a role of JP2 in cardiac myocytes where LTCCs regulate RyR2 not directly but indirectly through Ca²⁺-induced Ca²⁺ release (CICR). Nonetheless, JP2Δ427 also significantly reduced the peak twitch calcium transient of ventricular myocytes and the fractional shortening of the left ventricle from 43 to 31% without causing overt heart failure. Interestingly, it recruited LTCCs to the surface sarcolemma from T-tubules without disrupting T-tubules. Therefore, JP2 supports the cardiac ECC by aligning LTCC and RyR2 within an adequate distance for CICR. In this symposium, we will discuss how JPs regulates ECC of striated muscles.

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Aureobasidium pullulans is a yeast-like fungus commonly found in a variety of cosmopolitan environments such as plant leaf, soil, and damp indoor surface. In this investigation, Aureobasidium spp. were isolated from bathroom surfaces in several locations in Bangkok, Thailand and they were subsequently examined for antifungal agent production. Ten isolates obtained included KT1, BM1, PH1, TB1, , VM1, HKW1, HKW2, HKW3 and HKW4. All isolates were identified as A. pullulans based on morphological observations, physiological properties and exopolysaccharide characteristics (IR-spectra). The antifungal agents, extracted from their fungal cells, were tested for their antifungal activities against some Aspergillus spp. by using paper disc method. The extracts from A. pullulans KT1 and PH1 showed activities against A. fumigatus and A. flavus, respectively, while the extract from A. pullulans BM1 had activities against both A. fumigatus and A. flavus. For A. pullulans TB1, VM1 and , their extracts showed no inhibition activity against any of the Aspergilli tested. The extracts of A. pullulans isolates, containing antifungal activities, were further purified by using Thin Layer Chromatography (TLC) and High Performance Chromatography (HPLC) in comparison to the standard aureobasidin antibiotic.

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This article is a supplemental report for the determination of lead which has not yet be obtained for some of the standard rocks of GSJ in the earlier report.The sample was completely decomposed by gradual heating with HF, HNO₃ and HClO₄, and evaporated to dryness. In this report, the decomposing conditions for such special rocks as JF-1 and - were again examined. The decomposed sample was dissolved in 0.5 M HBr, spiked with ²¹²Pb and was passed through a column of Bio Rad AG1-X8 100200 mesh (4 mm i.d.×4cm h). Lead retained on the column was eluted with 6 M HCl after washing the column with 0.5 M HBr. The column yield of the purified lead solution was measured using ²¹²Pb activity and then subjected to the lead concentration measurement by GFAAS. The lead values obtained for JA-2, JA-3, JB-1a, JF-1, JG-1a, JG-2, JG-3, - of GSJ standard rocks were 19.8, 6.5, 7.5, 33.1, 47.5, 27.6, 33.2, 12.4 and 0.12 ppm, respectively. These values coincided very well with the reported values.

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The release properties of theophylline (TP) from three different types of tablets were investigated, one using a carboxyvinylpolymer (Carbopol^®: CP) as a matrix material and/or as a coating material. CP-matrix tablets were prepared from TP, lactose, and CP by the direct compression method. CP-coated tablets were prepared by spraying an aqueous solution or dispersion of CP onto core tablets containing TP. CP-coated matrix tablets (CM tablets) were prepared by spraying CP aqueous dispersion onto CP-matrix tablets. TP release profiles from each type of the tablet were studied by the JP 13 paddle method, using

st fluid (pH 1.2), purified water, and JP 2nd fluid (pH 6.8) as the dissolution media. The swelling behaviors of the tablets in each of the dissolution media were observed. When CP was used as a matrix material, TP release was retarded in the JP 2nd fluid. On the other hand, when CP was used as a coating material, the release was slowed in both st fluid and purified water. TP release from the CP-matrix tablet and CP-coated tablet varied depending on the addition amount and the grade of CP. When CP was used in the combination, TP release was retarded in all dissolution media. Furthermore the difference in TP release, depending on the dissolution medium, was decreased. These results suggest that it is feasible to control drug release in various pH environments by using CP as a matrix material, coating material, or both and by varying the addition amount and the grade of CP.

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Based on the moisture control system developed previously, we have already reported that the operational moisture content during aqueous polymeric coating by a type of fluidized bed should be controlled for a better coating efficiency.In this paper, effects of operational moisture content and agitator rotational speed on the properties of granules prepared by the aqueous polymeric coating were investigated experimentally, and optimization of this process was conducted. Core granules (mean diameter 600 μM) containing a model drug, pigment Blue No. 1, were coated with the aqueous dispersion of enteric polymer (Eudragit L30D) by the tumbling fluidized bed with controlling the operational moisture content. The coated granules were evaluated by dissolution tests in st (pH 1.2) and 2nd fluid (pH 6.8) and by agglomeration tendency. Film thickness and specific surface area of the granules were examined to discuss the film forming process. Based on the evaluation, effects of the operational variables on the drug release rate and agglomeration tendency were investigated. It was found that the drug release rate was suppressed with increase in moisture content at any rotational speed in the st and 2nd fluid, and the agglomeration tendency was prevented with increase in moisture content and agitator rotational speed. It was concluded from the results that the aqueous coating with the enteric polymer by the tumbling fluidized bed process should be carried out under a condition of moisture content between 12 and 14% with agitation below 5 rps.

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心筋や骨格筋には，細胞膜と筋小胞体が近接する結合膜構造が存在する．細胞膜上のL型カルシウムチャネル（LTCC）と筋小胞体膜上のリアノジン受容体は，この部位に集積し機能的複合体を形成している．これらのイオンチャネルの結合膜構造への集積は，正常な興奮収縮連関に必要不可欠であるが，その機構の詳細は不明である．結合膜構造を維持する分子として，ジャンクトフィリン（JP）が知られている．JPには4つのサブタイプが存在し，骨格筋には

とJP2が，心筋にはJP2が発現している．本研究ではLTCCの局在や機能におけるJPの役割について検討を行った．骨格筋芽細胞由来の筋管に，のC末端欠失変異体（ΔCT）を導入すると，LTCCの結合膜への集積が阻害された．また，免疫沈降法，プルダウンアッセイを行い，LTCCのポアを形成するCa_V1.1（別名：α_1S）サブユニットのC末端とJPが物理的に結合していることを明らかにした．さらにアデノ随伴ウイルスベクター（AAV）を用いてΔCTをマウス筋に発現させると，LTCCの細胞内局在の異常，細胞内Ca^2＋上昇の抑制，筋収縮力の低下が認められた．次に，類似の方法で心筋におけるJPの役割を検討した．JP2のC末端欠失変異体をマウス心筋に強制発現すると，心重量の増加，左室内径短縮率の有意な低下が認められた．単離心筋細胞を用いた検討では，細胞内Ca^2＋上昇の抑制が認められた．また，免疫細胞染色によりLTCCについて検討を行ったところ，コントロールと比較して表面細胞膜により多く局在していた．以上より，横紋筋においてJP変異体はドミナントネガティブ様の作用を示し，LTCCの正常な細胞内局在を阻害することで，Ca^2＋代謝や筋収縮力の低下を誘導することが示された．このことから，横紋筋におけるJPとLTCCの物理的な結合が，正常な筋収縮に重要な役割を果たしていることが示唆された．

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Jo-zai or tablet is a most popular form of pharmaceutical dosage in modern Japan. The term jo-zai first appears in the Japanese Navy Pharmacopoeia, First Edition (1872). Its Latin name was translated as torikisuki and was written in Japanese katakana characters. Jo-zai translated as trochischi can also be found in the Japanese Pharmacopoeia, First Edition () (1897)． Its Latin name and definition have changed several times : trochisichi ; pastilli, JP3 (1906) ; tablettae, JP5 (1932) ; tabellae : JP6 (1951), etc． The etymon of the word jo-zai is based on the English word, lozenge. Its square-shaped form is similar to old Japanese silver coins. During Japan's Edo era (1603-1868) and in ancient China, silver coins were called jo. Therefore the word lozenge was translated into Japanese as jo-zai，combining the character for coin with the one for drug, zai.

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  The dissolution profiles of paliperidone from INVEGA^® 3-mg tablets, osmotic-controlled release tablets, were evaluated by using the reciprocating cylinder method (RC method). We used 4 different compositions of the dissolution fluids, by considering the environment of the tablet in the gastrointestinal tract. After a lag time of 2 to 4 h, paliperidone was approximately dissolved to 24 h by zero-order release. The dissolution characteristics of paliperidone were not affected by the kind of the test medium, pH, and surfactant. In addition, the dissolution of the tablets was evaluated using the paddle method in distilled water, Japanese Pharmacopeia () st test fluid, and JP 2nd test fluid. The dissolution profiles of paliperidone obtained using the RC method and the paddle method were very similar. Further, the dispersion of the percentage of the dissolved paliperidone obtained using the RC method and the paddle method was small.

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