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We previously found that a single dose of B-type procyanidin mixture increase in skeletal muscle blood flow (BF). We compared BF changes following administration of (-)-epicatechin (EC, monomer) and the B-type procyanidins procyanidin B2 (B2, dimer), procyanidin C1 (C1, trimer), and cinnamtannin A2 (A2, tetramer). Each chemical was administered orally to rats, followed by BF measurement in cremaster arteriole for 60 min. About 10 and 100 µg/kg of B2 and C1 elicited BF increase, the effect was potent at 100 µg/kg. BF also increased significantly after administration of 10 µg/kg A2, but not with the administration at 100 µg/kg. EC yielded no BF changes. Co-treatment with the nonselective adrenaline blocker carvedilol attenuated the BF increase seen with 10 µg/kg A2 treatment. This outcome suggested the involvement of sympathetic nerve activation in the BF increase by this dose of A2. Co-treatment of 100 µg/kg A2 with the α2 blocker yohimbine exhibited an increase of BF significantly. The α2 adrenaline receptor in the vasomotor centre is an inhibitory receptor and it regulates hemodynamics. This result suggested that high doses of A2 did not alter BF because of activating the α2 adrenergic receptor. Phosphorylation of aortic endothelial nitric oxide synthase (eNOS) increased with 10 µg/kg A2 alone or co-treatment with 100 µg/kg A2 and yohimbine, but not with co-treatment of 10 µg/kg A2 and carvedilol or 100 µg/kg A2 alone. These results imply that A2 does not directly activate eNOS, but that shear stress from the increased BF might be associated with eNOS phosphorylation.

It is known that administering a gavage to rodents evokes a cardiac reflex, due to gastrointestinal stimulation. Consequently, it is difficult to evaluate changes in hemodynamics after a single oral dose of a pungent or astringent, which alters the circulation by increasing sympathetic activity. In the present study, we developed a method for administering a gavage without significantly affecting hemodynamics measurements. We marked a gastric tube at 10 cm from the tip, to mark the distance from the oral cavity to the stomach body of Wistar male rats. Rats were intubated under urethane anesthesia.After 10–15 min of stabilization, we measured the mean blood pressure (MBP), heart rate (HR), and blood flow (BF) in the cremaster arteriole under two different conditions; condition 1: a pointed gastric tube, room temperature distilled water, and injected at normal speed (approximately 3 ml/min); condition 2: a rounded gastric tube, 37°C distilled water, and injection at 1.0 ml/min. Under condition 1, we observed striking hemodynamic alterations, due to the somatic afferent reflex. In contrast, under condition 2, these hemodynamic changes were nearly eliminated. In addition, we could clearly detect hemodynamic changes in rats after a single gavage treatment of pungent (capsaicin) or astringent (cinnamtannin A2). We observed transient increases in the HR and MBP soon after treatment with capsaicin. Moreover, cremasteric BF was elevated with cinnamtannin A2. These results confirmed the utility of the gavage method developed in this study.

In this study, the effects of chitosan and surface-deacetylated chitin nanofibrils (SDACNFs) on hair growth were evaluated. In human follicle dermal papilla cells in vitro, chitosan and SDACNFs were shown to increase cell growth on day 3 after the initiation of treatment, together with an increase in the production of fibroblast growth factor-7 (FGF-7) by these cells on day 3. Furthermore, in an in vivo study in mice, chitosan and SDACNF application promoted hair growth. The number of anagen follicles significantly increased compared with that in the control group, whereas the number of telogen follicles significantly decreased in the chitosan and SDACNF groups. In the chitosan and SDACNFs groups, moreover, the expression levels of FGF-7 and Sonic hedgehog were significantly upregulated in hair follicles. Overall, our results demonstrated that chitosan and SDACNFs promoted hair growth and therefore may have applications as novel therapeutic agents for the treatment of hair loss in patients.

Acylated anthocyanins are more stable than monomeric anthocyanins, but little is known about their physiological effects. We evaluated the hemodynamic effects of single intragastric doses of purple carrot (Daucus carota L.) anthocyanin (PCA) and two monomeric anthocyanins, cyanidin 3-O-glycoside (C3G) and delphinidin 3-O-ruthenoside (D3R). PCA, C3G, or D3R was administered orally to rat and blood flow in the cremaster artery was measured for 60 min using a laser Doppler blood flow meter. After measurements, the aorta of the animal was removed and the extent of phosphorylation of aortic epithelial nitric oxide synthase (eNOS) and Akt were determined by western blotting. PCA (10 mg kg-1) or C3G (1 mg kg-1) significantly increased rat cremaster arteriole blood flow and phosphorylation of eNOS and Akt; D3G (1 mg kg-1) only slightly altered cremaster arteriole blood flow and did not affect the phosphorylation of eNOS and Akt in the aorta. These results suggest that hemodynamic alterations depend more on the chemical structure of anthocyanins, particularly the aglycon, than on the glycoside. In addition, increase of blood flow by a single oral dose of PCA was practically reduced with treatment of carvedilol (CR), a non-specific adrenaline blocker. Blood concentrations of cyanidin or its glycoside 15, 30, or 60 min after the administration of 10 mg kg-1 PCA were below the limit of detection. These hemodynamic changes may have been associated with an indirect adrenergic action induced following a single dose of PCA.

Two Y-shaped molecules combining two dissimilar (hydrophilic and hydrophobic) units with a reactive triethoxysilane moiety were synthesized by Michael addition reaction of (aminopropyl)triethoxysilane with 2-hydroxyethyl acrylate (HEA), followed by the addition of 2,2,2-trifluoroethyl acrylate (TFEA) or 1 H ,1 H ,5 H -octafluoropentyl acrylate (OFPA). Hydrolytic condensations of the Y-shaped triethoxysilane precursors proceeded as homogeneous systems in acetone in presence of the acidic catalyst to afford amphiphilic silsesquioxane nanoparticles (SQ-NPs) having hydroxyl and fluoroalkyl groups (HEA/TFEA-SQ and HEA/OFPA-SQ). Scanning force microscope (SFM), X-ray diffraction (XRD), and size-exclusion chromatography (SEC) measurements indicated the formation of nanoparticles (average particle diameter is about 2.0 nm) with reasonable molecular weights and low dispersities ( M n = 5100-5400, M w / M n = 1.22–1.36) without aggregation. Characteristic assembled structures and surface properties of the amphiphilic SQ-NPs in different solvents were also evaluated. Flexible self-standing films were obtained from the amphiphilic SQ-NPs without any additional compounds, which are due to intermolecular hydrogen bondings.

Currently, in Japan, women are required to participate and advance in the workplace because of the decline in the labor population. However, it is very difficult for them to do so because of the patriarchal system within Japanese history. In the 1990s, local governments began various projects to encourage women to participate in society. At the same time, local government administrations were introduced to project evaluation to boost the efficiency of their projects. However, project evaluation did not function well because project evaluation needs to be linked to outcomes of the program, and the outcome step was often performed independently. The purpose of this paper is to show how to perform project evaluation to promote women’s active participation in society in Japan. Using the Analytic Hierarchy Process, we show how to evaluate projects in a way that can connect to the outcomes of the program. This framework can also be used to calculate the degree of contribution of projects in the program from two perspectives. First, the decision makers in a local government evaluate the outcomes of the program and second, the people in charge of the projects that make up the program do the evaluation for their own projects. In this paper, we evaluated actual projects of a city in Japan and were able to show the direction they should take, such as reduction or expansion for each project in the next fiscal year, by using numerical values obtained in the process of calculation by this framework.

This study examines the change in the spatial patterns of demographic structure in central Tokyo since the period of the bubble economy in the late 1980s. To this end, we analyze grid square data suitable for time-series analysis between 1985 and 2005, using Geographic Information Systems (GIS). After selecting major indicators representing three dimensions of the social area analysis – family status, socio-economic status, and ethnic status – we map each indicator and make quantitative comparisons between zones of distance and direction from Tokyo’s city center. Focusing on the spatial pattern of population change in the 23 wards between 1985 and 2005, analysis reveals that central Tokyo experienced a population recovery from the latter half of the 1990s, having previously faced a continuing population decline until 1995. On the basis of this population change trend, we examine the spatial pattern of each indicator in the social atlas. Concerning age and household composition, their spatial distribution has gradually shifted from a zonal pattern to a sectoral one, due to the migration of younger nuclear families to the area surrounding the city center. The spatial distribution of socio-economic status, represented by the occupational structure, maintained a sectoral pattern characterized by the contrast between the eastern and western parts of Tokyo, although this distinction has blurred. In particular, the number of managers and officials in the 23 wards has decreased and its distribution shifted to a zonal pattern, indicating the polarization of white-collar workers. The distribution of foreigners shows a zonal pattern, in which the highest value appeared in the area surrounding the city center. However, spatial autocorrelation analysis of the distribution of four major nationalities reveals a clustered pattern, supporting the findings of previous studies in Western countries.

After the bubble economy collapsed at the beginning of the 1990s, the government’s deregulation policies accelerated urban development in the Tokyo Metropolitan Area. This resulted in increased trade in real estate and accelerated population growth in downtown Tokyo. However, that trend was not observed in all areas: instead, it exacerbated the spatial differentiation that was already apparent in the Tokyo Metropolitan Area. Hirayama (2005, 2006, 2011) found that government policy to promote housing supply and increase urban redevelopment split urban space into hot spots, with new investments, and redeveloped districts and cold spots, with stagnant and depopulated districts. However, the precise locations of such spots are not obvious, as those studies did not map them.This study identified and mapped hot and cold spots in Tokyo with the use of spatial analysis with GIS. To this end, we employed grid square population statistics for 1985, 1995, and 2005, which encompasses the entire period of the bubble economy and its aftermath. The analysis of hot spots using the Getis-Ord Gi* statistic was performed on data for population change in 23 wards of Tokyo in this period. Then, we explored the detailed composition of the population and the background of the changes in a consideration of the socio-economic shift of Tokyo during this period.The results of the analysis indicated that hot and cold spots coexisted in central Tokyo, and their spatial distribution changed drastically following the collapse of the bubble economy at the beginning of the 1990s. Between 1985 and 1995, populations show a concentric pattern of change: cold spots are observed in areas close to the city center and hot spots appear on the outskirts of the study area. This pattern is a result of population outflows due to soaring land prices during the period of the bubble economy.However, population changes between 1995 and 2005 indicated a different pattern and the resulting distribution of hot and cold spots was dispersed. Specifically, hot spots appeared in the south and east parts of central Tokyo, where highrise condominiums were being built on the sites of former factories or warehouses in the coastal areas of Tokyo Bay. In these districts, a marked increase of white-collar workers was observed, an indicator of gentrification. By contrast, cold spots are noted on the northern side of central Tokyo, where large public housing estates are located and their population has declined and aged. The contrast between the north and the south of Tokyo became obvious after the bubble economy collapsed.

Novel sulfur-containing silsesquioxane nanoparticles, (RS–SiO1.5)n, having uniform size distribution, good solubility, and relatively high refractive index were synthesized by hydrolytic condensation of a triethoxysilane precursor derived from glycidol, followed by the esterification with sulfur-containing acid chlorides. Esterification of the water-soluble silsesquioxane nanoparticles with 3-(methylthio)propionyl chloride afforded silsesquioxane hybrid with a high density of chemically bonded peripheral methyl thioether groups, which was characterized by 1H, 13C NMR, Fourier transform infrared spectroscopy, and thermogravimetric analysis measurements. The resulting product was soluble in various organic solvents, such as CHCl3, acetone, tetrahydrofuran, dimethyl formamide, and dimethyl sulfoxide. The size of the sulfur-containing nanoparticles evaluated by X-ray diffraction was 2.1 nm. Transmission electron microscopy, gel permeation chromatography, and dynamic light scattering measurements indicated the formation of the nanoparticles having relatively narrow size distribution with an average particle diameter of less than 3 nm without aggregation. The sulfur content of the methyl thioether-containing silsesquioxane hybrid analyzed by elemental analysis was 16.1 %, which led to relatively high refractive index (nD = 1.588) and high Abbe number (34.4). Two sulfur-containing silsesquioxane hybrids with peripheral thiophene and phenyl thioether moieties were also obtained by the same procedure, and resulting hybrids showed high refractive indices of 1.605 and 1.627, and Abbe numbers of 31.8 and 24.3, respectively.

Amphiphilic silsesquioxanes-based hybrids were synthesized by hydrolytic co-condensation of a hydroxyl-functionalized triethoxysilane precursor derived from 2-hydroxyethyl acrylate (HEA) and fluorinated triethoxysilane precursors derived from 1H,1H,5H-octafluoropentyl acrylate (OFPA) and 2,2,2-trifluoroethyl acrylate (TFEA). Hydrolytic co-condensations of two functionalized triethoxysilane precursors proceeded as homogeneous systems in N,N-dimethylformamide (DMF) to afford amphiphilic silsesquioxanes hybrids, which were soluble in a variety of solvents, depending on the composition. The structure of the constitutional unit of the hybrids was confirmed by the results of NMR and FT-IR measurements. Scanning force microscope (SFM) measurements indicated the formation of spherical hybrids having relatively narrow size distributions (average particle diameter < 3.0 nm) without aggregation. The sizes of the hybrids were also confirmed by X-ray diffraction (XRD). Flexible semitransparent films were obtained from the amphiphilic silsesquioxane hybrids prepared by hydrolytic co-condensations at suitable feed ratios. The organic-inorganic amphiphilites exhibited a high density of chemically bonded peripheral fluoroalkyl and hydroxyalkyl groups, in which various characteristic properties involving amphiphilicity, film-forming property, refractive index, responsive surface, nanometer size, and narrow size distribution can be manipulated by varying the composition in the feed.

Cynomolgus monkeys [Macaca fascicularis (mf)] are widely used to determine pharmacokinetics and toxicological potential of many drug candidates as human models in the drug discovery and development. Cytochrome P450s (P450, CYP), one of the most important enzymes in drug metabolism, in monkey livers are generally similar to corresponding human P450s exhibiting high degrees of homologies in cDNAs and amino acid sequences. Species differences regarding important liver P450 3A and 2D function were examined between cynomolgus monkeys and humans using typical human P450 probe reactions using midazolam (a P450 3A marker), dextromethorphan and bufuralol (P450 2D markers). P450 3A-mediated midazolam 1'-hydroxylation activities in liver microsomes from individual monkey were highly correlated with midazolam 4'-hydroxylation activities but not correlated with dextromethorphan N-demethylation activities. Recombinant monkey CYP2D17 and CYP2D44 catalyzed dextromethorphan O- and N-demethylations as well as monkey mfCYP3A4 and mfCYP3A5 did. On the other hand, contributions of corresponding P450 2D6 and P450 3A4/5 to dextromethorphan N- and O-demethylations, in human liver microsomes were negligible under the present conditions. From these results, monkey P450 2D and 3A enzymes might have broader substrate specificity toward dextromethorphan oxidation than those in human livers. Special attention should be paid when enzymatic and pharmacokinetic data are extrapolated from monkeys to humans.

Drug metabolizing activities of cytochromes P450 (P450s, or CYPs) 3A4 and 3A5 in liver microsomes from the cynomolgus monkey [Macaca fascicularis (mf)] were investigated and compared with those of human P450 3A enzymes. Low activities for dealkylation of ethoxyresorufin and pentoxyresorufin were seen in recombinant monkey mfCYP3A4 and mfCYP3A5 and in recombinant human CYP3A4 and CYP3A5 expressed in bacterial membranes. Hydroxylation activities of mfCYP3A4 and mfCYP3A5 toward coumarin, paclitaxel, diclofenac, flurbiprofen, and S-mephenytoin were below detectable levels, as was also true for CYP3A4 and CYP3A5. Monkey mfCYP3A5 and mfCYP3A4 were highly active in bufuralol 1'-hydroxylation. mfCYP3A5 was efficient at dextromethorphan O-demethylation, although human CYP3A5 was unable to catalyze this reaction. Apparent bufuralol 1'-hydroxylation and dextromethorphan O-demethylation activities of monkey liver microsomes were higher than those of human liver microsomes, possibly because of contributions of mfCYP3A5 to these P450 2D-dependent drug oxidations. mfCYP3A5 and CYP3A5 catalyzed midazolam 1'-hydroxylation at a low substrate concentration more efficiently than the corresponding CYP3A4. mfCYP3A5 had higher testosterone 6beta-hydroxylase activity than mfCYP3A4, but the reverse relationship was observed in oxidation of nifedipine and hydroxylation of dexamethasone. These results demonstrate that monkey P450 3A enzymes have similar substrate selectivity to that of human P450 3A enzymes, but exhibit wider substrate selectivity toward P450 2D substrates.

A 59-year-old man was referred for evaluation of nephrotic syndrome. The patient was diagnosed to have rheumatoid arthritis and had been treated for 10 years. Renal biopsy showed mesangial proliferation with small nodular formations, which were determined as fibrillary deposits (average diameter: 20 nm) by electromicroscopy. Congo-red stain was negative. The laboratory findings revealed hypocomplementemia and lambda type of Bence-Jones protein in urine without other systemic diseases including multiple myeloma. Immunosuppressive therapy did not attenuate the nephrotic-range proteinuria. Such a case of fibrillary glomerulonephritis with hypocomplementemia is rare.(Internal Medicine 42: 719-722, 2003)

In this paper, a new adaptive equalizer that adjusts the nonlinear filter without training signals is proposed and its performance is evaluated. In the proposed equalizer, the nonlinear filter has constraints, while learning is carried out by means of the output energy minimization algorithm. Since the proposed equalizer has nonlinearity, it has a better bit error rate than the linear equalizer. Further, since no training signal is needed, it is to be expected that the transmission efficiency is superior to that in an equalizer with training signals. In order to evaluate the performance limitations of the proposed equalizer, an optimum equalizer with constrained filter input is derived. By means of simulations, a performance evaluation is carried out and the effectiveness of the proposed equalizer is demonstrated. Further, in order to improve the performance of the proposed equalizer for a linear communication channel, an intersymbol interference canceler and an algorithm for correcting the error are proposed and their effectiveness is demonstrated. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(3): 17–29, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10145

This study examined the spatial patterns of the Tokyo metropolitan area in terms of the occupation structure and its transformation after the collapse of the bubble economy. To overcome technical problems of the previous studies on the urban spatial structure, we adopted grid square unit data and made analysis using spatial autocorrelation indices with geographic information systems. Spatial autocorrelation analysis of the spatial pattern of occupational structure in 2005 confirmed the findings obtained in previous studies. Hence, the basic spatial structure of social areas in the Tokyo metropolitan area has been maintained. However, the conventional finding, obtained from the analysis of administrative unit, that socioeconomic status shows a concentric pattern in the suburbs was not necessarily supported by the analysis of grid square units, which shows a radial pattern along the railroad lines. Particularly in the suburbs, the tendency of occupation groups to vary with the distance from the railroad has been strengthened. This suggests that not only “diversification” but also “polarization” of the suburbs has progressed.

Atrial fibrillation (AF) disrupts movement of the left atrium (LA) and worsens the vital prognosis by causing thromboembolism. Ultrasound Doppler measurement, phase-contrast magnetic resonance imaging (PC MRI), as well as computational fluid dynamics (CFD) have revealed hemodynamic changes in the LA due to AF, such as stagnation of blood flow in the left atrial appendage (LAA). However, quantitative evaluation of the hemodynamics during AF has not been conducted, and the effects of important AF characteristics, such as a lack of active contraction of the LA (atrial kick) in late diastole and the occurrence of high-frequency fibrillation (>400bpm) of the atrial wall, on blood flow field and concomitant hemodynamic stresses have not been completely understood. In this study, the effects of the above-mentioned two characteristic phenomena of AF on blood flow and hemodynamic parameters were quantitatively investigated. Based on MRI of a healthy volunteer heart, one healthy LA model and two AF models (one without atrial kick, and one without atrial kick and with high-frequency fibrillation) were constructed to perform hemodynamic analysis, and the computational results were compared. The results revealed that each characteristic phenomenon of AF influenced hemodynamics. Especially, atrial wall movement by high-frequency fibrillation had a large impact on the stagnation of blood flow. The relative residence time (RRT), which is an indicator of stagnation of blood flow, increased in the upper part of the LAA during AF. This result implies that there is a local thrombus-prone site in LAA when AF occurs.

This study investigated the prophylactic effects of orally administered surface-deacetylated chitin nanofibers (SDACNFs) and chitosan against 5-fluorouracil (5-FU)-induced intestinal mucositis, which is a common side effect of 5-FU chemotherapy. SDACNFs and chitosan abolished histological abnormalities associated with intestinal mucositis and suppressed hypoproliferation and apoptosis of intestinal crypt cells. These results indicate that SDACNF and chitosan are useful agents for preventing mucositis induced by anti-cancer drugs.

The left atrium (LA), which connects four pulmonary veins (PVs) to the left ventricle (LV), has a characteristic shape called the left atrial appendage (LAA) under the left PV. Atrial fibrillation (AF) is a heart disease, by which irregular electrical signals with high-frequency contraction (> 400 bpm) occur in the LA. Although AF itself is not fatal, it may cause thrombus formation, resulting to cerebral infarction. In this study, hemodynamics in the LA with/without AF was investigated by means of fluid-structure interaction simulation.Copyright © 2011 by ASME

To implement low-k1 lithography, it is most fundamental to reduce aberrations of projection lenses for the exposure tools, notonly in the optical design, but also in the manufacturing process. This paper will reveal a new lens manufacturing conceptutilizing Zernike circle polynomials to overcome such difficulties. Sets of Zernike coefficients are used to describe the surfaceaccuracy of each element or wavefront aberrations of assembled lens, and each coefficient itself becomes the target of elementpolishing or lens tuning. Adopting these targets is the most effective way to control actual optical performance and results in agreat improvement of the projection lenses. We present some topics of our new manufacturing process and the performanceprogress up to our latest KrF stepper, FPA-3000EX6.Keywords: optical lithography, projection lens, wavefront aberration, Zernike circle polynomials 1. INTRODUCTION The shrinkage of pattern size in semiconductor devices requires extremely high performance of the exposure tools in thelithography process. In particular, a variety of low-k1 lithography techniques such as oblique illumination or phase shift masksrequires very small aberrations of the projection lenses. Both optical design and the manufacturing process are important forthe improvement of projection lenses offered for current lithography. The technology of lens design has greatly improved