18 results on '"Daisuke WATANABE"'
Search Results
2. The influence of androgen deprivation therapy on hip geometric properties and bone mineral density in Japanese men with prostate cancer and its relationship with the visceral fat accumulation
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Kunihisa Miura, Akio Mizushima, Takahiro Kimura, Tadaaki Minowa, Daisuke Watanabe, and Akemi Yamashita
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Male ,musculoskeletal diseases ,medicine.medical_specialty ,030232 urology & nephrology ,030209 endocrinology & metabolism ,Intra-Abdominal Fat ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,Absorptiometry, Photon ,0302 clinical medicine ,Japan ,Bone Density ,Internal medicine ,medicine ,Humans ,Visceral fat ,Retrospective Studies ,Bone mineral ,business.industry ,Prostatic Neoplasms ,Section modulus ,Androgen Antagonists ,medicine.disease ,Endocrinology ,Androgens ,Osteoporosis ,Geriatrics and Gerontology ,business ,Visceral Obesity - Abstract
The influence of androgen deprivation therapy (ADT) for prostate cancer on the hip geometric properties evaluated by dual-energy X-ray absorptiometry (DXA) has not yet been demonstrated. This study aimed to investigate the changes in these properties after 1 year of ADT. A total of 65 Japanese men with prostate cancer who underwent ADT for the first time in our facility were included in the study. The hip geometric parameters and the bone mineral density (BMD) taken before and after 1 year of ADT were retrospectively examined. With ADT, we not only confirmed significant BMD annual changes in the lumbar spine, the femoral neck, and the total hip of -1.65%, -1.91%, and -2.20%, respectively, but we also confirmed significant annual changes in cross-sectional areas, cross-sectional moments of inertia, and section modulus in the narrow femoral neck of -2.55%, -3.50%, and -3.14%, respectively. The annual rate of decrease in the femoral neck BMD was significantly higher in patients with visceral fat obesity than in those without visceral obesity (-1.79% vs. -0.28%). One year of ADT for Japanese men with prostate cancer might decrease the strength of bending and the structural rigidity as well as BMD at the femoral neck.
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- 2020
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3. Application of fluoride volatility method to the spent fuel reprocessing
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Daisuke Watanabe, Tetsuo Fukasawa, Akira Sasahira, and Kuniyoshi Hoshino
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Nuclear and High Energy Physics ,Materials science ,Waste management ,010308 nuclear & particles physics ,0211 other engineering and technologies ,02 engineering and technology ,01 natural sciences ,Spent nuclear fuel ,Fluoride volatility ,Adsorption ,Nuclear Energy and Engineering ,0103 physical sciences ,Mixed oxide ,Light-water reactor ,021108 energy ,Solvent extraction ,MOX fuel - Abstract
An advanced reprocessing system has been developed to treat various SF (spent fuels): spent UO2 and MOX (mixed oxide) fuels from LWR (light water reactor) and MOX fuel from FR (fast reactor). The s...
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- 2019
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4. Loss of Rim15p in shochu yeast alters carbon utilization during barley shochu fermentation
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Dai Shintani, Satoshi Tashiro, Yasuhiro Kajiwara, Hideharu Takashita, Daisuke Watanabe, Akihiko Iwami, Yukiko Sugimoto, and Hiroshi Takagi
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0301 basic medicine ,Saccharomyces cerevisiae Proteins ,Genes, Fungal ,030106 microbiology ,Saccharomyces cerevisiae ,Ethanol fermentation ,Applied Microbiology and Biotechnology ,Biochemistry ,Analytical Chemistry ,Carbon utilization ,03 medical and health sciences ,chemistry.chemical_compound ,Glycerol ,Food science ,Sugar ,Molecular Biology ,biology ,Chemistry ,business.industry ,Organic Chemistry ,food and beverages ,Hordeum ,General Medicine ,biology.organism_classification ,Carbon ,Yeast ,030104 developmental biology ,Fermentation ,Brewing ,business ,Protein Kinases ,Biotechnology - Abstract
Rim15p of the yeast Saccharomyces cerevisiae is a Greatwall-family protein kinase that inhibits alcoholic fermentation during sake brewing. To elucidate the roles of Rim15p in barley shochu fermentation, RIM15 was deleted in shochu yeast. The disruptant did not improve ethanol yield, but altered sugar and glycerol contents in the mash, suggesting that Rim15p has a novel function in carbon utilization.
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- 2019
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5. Nitrous acid generation from radiolysis of nitric acid aqueous solution under gas flow condition
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Yoichi Wada, Masashi Itori, Tetsunari Ebina, Daisuke Watanabe, and Akira Sasahira
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inorganic chemicals ,Nuclear and High Energy Physics ,Nitrous acid ,Aqueous solution ,Volatilisation ,010304 chemical physics ,Chemistry ,organic chemicals ,Radiochemistry ,02 engineering and technology ,equipment and supplies ,021001 nanoscience & nanotechnology ,01 natural sciences ,chemistry.chemical_compound ,Nuclear Energy and Engineering ,Nitric acid ,0103 physical sciences ,Radiolysis ,bacteria ,Nitrogen oxide ,Irradiation ,0210 nano-technology ,Volatility (chemistry) ,Nuclear chemistry - Abstract
To understand the radiolysis of nitric acid in the volatility condition of nitrous acid, which commonly occurs in a spent fuel reprocessing plant, an irradiation experiment of nitric acid aqueous solution was carried out under a gas flow condition into a solution. In our experiment, the volatilized and dissolved nitrous acid amounts were measured separately. The G-value of nitrous acid generation, evaluated by the total generated nitrous acid amount and the absorbed dose, was consistently about 0.8 molecules/100 eV for 4 mol/L (M) of nitric acid concentration even if the ratio of volatilized nitrous acid to total nitrous acid varied over 50% and the dose rate was varied from 0.13 to 1.2 kGy/h. The dependence of the G-value on the nitric acid concentration was also unaffected by the volatilization of the nitrous acid and was almost equal to the reported values. The highest apparent equilibrium constant of nitrous acid volatilization in our experiment under 50 °C and 4 M of nitric acid concentration...
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- 2016
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6. GSK2656157, a PERK inhibitor, reduced LPS-induced IL-1β production through inhibiting Caspase 1 activation in macrophage-like J774.1 cells
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Naoki Koide, Takashi Yokochi, Takayuki Komatsu, Yoshikazu Naiki, Takashi Ando, Daisuke Watanabe, and Kazuko Takahashi
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Lipopolysaccharides ,0301 basic medicine ,Indoles ,Thapsigargin ,Lipopolysaccharide ,Interleukin-1beta ,Immunology ,Caspase 1 ,Priming (immunology) ,Toxicology ,Cell Line ,Proinflammatory cytokine ,Mice ,eIF-2 Kinase ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Immunology and Allergy ,Pharmacology ,Chemistry ,Adenine ,Macrophages ,Endoplasmic reticulum ,Inflammasome ,General Medicine ,Cell biology ,Enzyme Activation ,030104 developmental biology ,Biochemistry ,Unfolded protein response ,030215 immunology ,medicine.drug - Abstract
IL-1β is one of the inflammatory cytokines and is cleaved from pro-IL-1β proteolytically by activated Caspase 1. For the activation of Caspase 1, inflammasome was formed by two signals, what is called, priming and triggering signals. In this study, it was found that mouse macrophage J774.1 cells, when treated by single large amount of lipopolysaccharide (LPS), produced a significant amount of IL-1β. On the other hand, IL-1β production was not detected when treated by a single, small amount of LPS. Then, focusing on endoplasmic reticulum (ER) stress response among stress responses induced by a large amount of LPS, when GSK2656157, a PERK inhibitor, was used for inhibition of ER stress, GSK2656157 reduced IL-1β production dose-dependently. Next, when Thapsigargin, an ER stress reagent, was added with LPS, IL-1β production increased more than by LPS alone. Thus, these results suggested that ER stress was involved in LPS-induced IL-1β production. When the activation of Caspase 1 was examined by fluorescence activated cell sorter analysis, it was found that GSK2656157 inhibited LPS-induced Caspase 1 activation. Further, it was confirmed that GSK2656157 did not affect LPS-induced TNF-α production and activation of NF-κB and specifically inhibited the PERK/eIF-2α pathway. Therefore, it was found that GSK2656157 specifically inhibited ER stress induced by large amount of LPS and reduced LPS-induced IL-1β production through inhibition of Caspase 1 activation.
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- 2016
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7. Experimental study on elemental behaviors in fluorination of nuclear spent fuel with flame reactor
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Kuniyoshi Hoshino, Daisuke Watanabe, Yuko Kani, Akira Sasahira, and Fumio Kawamura
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Nuclear and High Energy Physics ,Nuclear fission product ,010405 organic chemistry ,Chemistry ,010401 analytical chemistry ,Inorganic chemistry ,Radiochemistry ,chemistry.chemical_element ,Partial pressure ,01 natural sciences ,Spent nuclear fuel ,0104 chemical sciences ,Rubidium ,chemistry.chemical_compound ,Nuclear Energy and Engineering ,Molybdenum ,Scientific method ,Light-water reactor ,Fluoride - Abstract
Our proposed spent nuclear fuel reprocessing technology named FLUOREX is a hybrid system based on reprocessing technologies of fluorination and solvent extraction for light water reactor fuel. In the current research, we experimentally clarified solid–gas transfer behaviours of the fluorides in the FLUOREX process and identified the volatile and non-volatile compounds in the fluorination. We carried out a fluorination experiment for simulated spent nuclear fuel and solid separation from the UF6 gas stream. The distribution ratios of fission product elements in the experimental apparatus were evaluated. Molybdenum, Te, Nb, and Ru were volatilized by fluorination and they accompanied the UF6 gas. However, 22.9% of the Ru and 3.4% of the Nb were retained as solids in the experimental apparatus, contrary to the fact that their partial pressures in the experiment were lower than their vapor pressures. Rubidium, Sr, Zr, Ce, and Nd were completely recovered as solid fluorides, and these results agreed with the p...
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- 2015
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8. Force estimation via physical properties of air cushion for the control of a human-cooperative robot: basic experiments
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Daisuke Watanabe, Hidetaka Nozawa, Suwoong Lee, and Kenji Inoue
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Engineering ,business.industry ,Constraint (computer-aided design) ,Mechanical engineering ,Pneumatic pressure ,Structural engineering ,Computer Science Applications ,law.invention ,Cylinder (engine) ,Human-Computer Interaction ,Piston ,Hardware and Architecture ,Control and Systems Engineering ,law ,Robot ,Air cushion ,business ,Nonlinear elasticity ,Software - Abstract
For the control of a human-cooperative robot (HCR) using a soft material, we aim to verify, in this study, the usefulness of force estimation via physical properties of an air cushion. First, the physical model of the air cushion was represented by an air cylinder with a piston, which is subject to constraint by nonlinear elasticity. Second, the elastic properties of the air cushion were examined under the assumption that it can be formulated by a function of pneumatic pressure. The force applied to the air cushion was next estimated on the basis of the physical model, and the HCR was successfully controlled according to the estimated force.
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- 2015
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9. Characteristic of Passenger's Route Selection and Generation of Public Transport Network
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Takahiro Majima, Mitujiro Katuhara, Daisuke Watanabe, and Keiki Takadama
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Transport engineering ,Engineering ,Service (systems architecture) ,business.industry ,ComputerApplications_MISCELLANEOUS ,Multi-agent system ,Range (aeronautics) ,Container (abstract data type) ,ComputerApplications_COMPUTERSINOTHERSYSTEMS ,Mass transportation ,Public transport network ,business ,Selection (genetic algorithm) - Abstract
Scheduled liner service is a proper system for mass transportation and it is employed by wide range of transportation modes, such as railway, airline, maritime container shipping and bus. To get mo...
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- 2015
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10. Effects of a soybean nutrition bar on the postprandial blood glucose and lipid levels in patients with diabetes mellitus
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Koichiro Hamada, Daisuke Watanabe, Tsuneyuki Noda, Motonobu Sugimoto, Yoshihisa Urita, and Soh Iwashita
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Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,chemistry.chemical_compound ,Insulin resistance ,Japan ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Aged ,Dyslipidemias ,Aged, 80 and over ,Meal ,Cross-Over Studies ,Triglyceride ,business.industry ,Insulin ,Soy Foods ,Middle Aged ,medicine.disease ,Lipids ,Crossover study ,Glycemic index ,Postprandial ,Endocrinology ,Diabetes Mellitus, Type 2 ,chemistry ,Glycemic Index ,Hyperglycemia ,Female ,Insulin Resistance ,Snacks ,business ,Food Science - Abstract
We investigated the influence of a soybean nutrition bar made from whole soy powder on the blood glucose, insulin and lipid levels in comparison with a test cookie with the same amount of energy in patients with diabetes mellitus. In the cross-over designed study, meal tolerance tests using the soybean nutrition bar and test cookie were performed. Two kinds of test meals were used: Study 1 80 kcal, Study 2 592 kcal. The blood glucose response was significantly lower in the soybean nutrition bar trial than in the cookie trial (Studies 1 and 2, p < 0.001). The blood insulin response was also significantly lower in the soybean nutrition bar trial than in the cookie trial (Study 2, p < 0.001). The blood triglyceride and non-esterified fatty acid responses were not significantly different between the two trials, nor were the changes in breath H₂ enrichment (Study 2). The soybean nutrition bar did not induce postprandial hyperglycaemia in diabetic patients unlike the isoenergetic test cookies.
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- 2012
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11. Adsorption of Molybdenum Hexafluoride on Magnesium Difluoride for Uranium Purification in FLUOREX Reprocessing
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Daisuke Watanabe, Fumio Kawamura, Akira Sasahira, and Kuniyoshi Hoshino
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Nuclear and High Energy Physics ,Nuclear fission product ,Inorganic chemistry ,chemistry.chemical_element ,Uranium ,Spent nuclear fuel ,Nuclear reprocessing ,chemistry.chemical_compound ,Fluoride volatility ,Adsorption ,Nuclear Energy and Engineering ,chemistry ,Molybdenum hexafluoride ,Fluoride ,Nuclear chemistry - Abstract
The nuclear fuel reprocessing method FLUOREX is a hybrid system based on fluoride volatility and using solvent extraction. Spent nuclear fuel is fluorinated, and most of the uranium is recovered as UF6 gas. UF6 contains some volatile fission product (FP) fluorides, so we considered their elimination from UF6 by adsorbing them on fluoride adsorbents. We experimentally examined the adsorption of MoF6 on MgF2 adsorbent; MoF6 is present as a volatile FP fluoride in UF6 produced by the fluorination of spent nuclear fuel. The adsorption isotherm of MoF6 adsorption on MgF2 was obtained at MoF6 pressures from 10−4 to 50 kPa. The saturated adsorption amount was 1:3 ± 0:4 mg/m2 at MoF6 pressures from 10−4 to 1 kPa. At MoF6 pressure of about 10−3 kPa, the saturated adsorption amount had no dependence on adsorption temperatures from 398 to 463 K. We deduced that MoF6 was adsorbed as a monomolecule layer on the MgF2 surface at MoF6 pressures from 10−4 to 1 kPa, and the MoF6 partial pressure in UF6 could be decreased b...
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- 2011
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12. Antioxidative Effects of Cherry Leaves Extract on tert-Butyl Hydroperoxide-Mediated Cytotoxicity Through Regulation of Thioredoxin-2 Protein Expression Levels
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Yuji Goto, Noriyuki Uemura, Masanao Niwa, Kazuhiro Hara, Daisuke Watanabe, Takeshi Yanagishita, Nobuhiko Taguchi, Masaaki Sakura, Masashi Kato, and Machiko Iida
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Programmed cell death ,Cell Survival ,DNA damage ,Health, Toxicology and Mutagenesis ,p38 mitogen-activated protein kinases ,Biology ,Toxicology ,p38 Mitogen-Activated Protein Kinases ,Antioxidants ,Cell Line ,Mitochondrial Proteins ,chemistry.chemical_compound ,Thioredoxins ,tert-Butylhydroperoxide ,Humans ,chemistry.chemical_classification ,Reactive oxygen species ,Plant Extracts ,fungi ,Glutathione ,Oxidants ,metropolitan_transit.transit_stop ,Up-Regulation ,Enzyme Activation ,Plant Leaves ,Oxidative Stress ,chemistry ,Biochemistry ,tert-Butyl hydroperoxide ,Melanocytes ,Prunus ,metropolitan_transit ,Thioredoxin ,Reactive Oxygen Species ,Cherry tree ,DNA Damage ,Phytotherapy ,Signal Transduction - Abstract
Components of cherry trees have been used as traditional herbal remedies for various diseases. These components are known to possess antioxidative effects. However, the mechanisms underlying cherry tree component-mediated antioxidative effects remain largely unknown. This study focused on cherry leaves extract (CLE) and examined the mechanism underlying the effect of CLE on tert-butyl hydroperoxide (t-BOOH)-induced melanocytic cell death with DNA damage. Interestingly, CLE prevented t-BOOH-induced cell death with reduction in DNA damage, p38 kinase activation, and reactive oxygen species (ROS) production. CLE-mediated suppression of cell death with reduction of DNA damage, p38 kinase activity and ROS production was prevented by a thioredoxin (Trx) system inhibitor but not by a glutathione (GSH) system inhibitor. Finally, data showed that CLE prevented t-BOOH-induced reduction of Trx2 but not Trx1 and Trx reductases (TrxR1 and TrxR2) protein expression. Thus, our results suggest that CLE prevents t-BOOH-induced reduction in Trx2 expression, promotion of ROS production, activation of p38 kinase, and increase in DNA damage and that it protects against cell death.
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- 2011
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13. Effects of process time and thread on tensile shear strength of Al alloy lap joint produced by friction stir spot welding
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Daisuke Watanabe, Mitsuo Fujimoto, Natsumi Abe, S Sato Yutaka, and Hiroyuki Kokawa
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Materials science ,Mechanical Engineering ,Metallurgy ,Alloy ,Metals and Alloys ,chemistry.chemical_element ,Welding ,Thread (computing) ,engineering.material ,Microstructure ,Surfaces, Coatings and Films ,law.invention ,Lap joint ,chemistry ,Mechanics of Materials ,law ,Aluminium ,visual_art ,Aluminium alloy ,visual_art.visual_art_medium ,engineering ,Composite material ,Spot welding - Abstract
In automotive applications, friction stir spot welding (FSSW) has been practically used in the construction of aluminium car bodies. In this study, the weld strength and factors governing the weld strength in the friction stir spot welded aluminium alloy 6061-T6 were examined. The weld strength increased with the process time during FSSW up to 3 s, beyond which it decreased. The fracture path changed from the lapped interface into the shoulder edge as the process time increased, and the maximum strength was obtained at the process time when the transition of the fracture path occurred. The cross-sectional microstructure depended on the threads on the probe surface, i.e. the elliptical zone was formed in the stir zone by the threads, but an effect of the thread on the weld strength was hardly found. The present study suggests that the weld strength was strongly related to the size of the well-consolidated region, which was larger than the elliptical zone observed in the vicinity of the exit hole.
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- 2010
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14. Laser Ablation Properties of JT-60 Re-deposited Carbon Layers
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Takahiro SHIBAHARA, Youichi SAKAWA, Daisuke WATANABE, Kazuyoshi SUGIYAMA, and Tetsuo TANABE
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Nuclear and High Energy Physics ,Nuclear Energy and Engineering - Published
- 2006
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15. Adsorption, activity, and kinetics of acid phosphatase as influenced by selected oxides and clay minerals
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Tatsuya Onaga, Daisuke Watanabe, Haruo Shindo, Osamu Nakahara, Qiaoyun Huang, and Makiko Urakawa
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biology ,Immobilized enzyme ,Kinetics ,Inorganic chemistry ,Oxide ,Acid phosphatase ,Soil Science ,Plant Science ,chemistry.chemical_compound ,Adsorption ,Montmorillonite ,chemistry ,biology.protein ,Allophane ,Clay minerals - Abstract
Abstrac The effects of 3 oxides (Fe, Al, and Mn oxides) and 3 clay minerals (kaolin, montmorillonite, and allophane) on the adsorption and subsequent kinetic properties of acid phosphatase were compared. The amount of enzyme adsorbed by the oxides and clay minerals followed the order: montmorillonite ≫ kaolin > Mn oxide > Fe oxide > Al oxide ≫ allophane. The adsorption isotherms of the enzyme on the oxides and clay minerals, except for montmorillonite and allophane, fitted the Langmuir equation. The activity of the enzyme immobilized by the inorganic components studied was in the order of allophane > kaolin > Fe oxide > montmorillonite > Al oxide ≒ Mn oxide. Compared to the free enzyme, the V max, Km, and V max / K m values of the immobilized enzyme decreased, increased, and decreased, respectively. Among the oxides or clay minerals, the higher the ability of the inorganic components to adsorb the enzyme, the lower the value of the V max / K m ratio of the immobilized enzyme. These findings suggest that t...
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- 2002
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16. Numerical analysis of neck propagation in polymeric materials. Part 2 – Neck propagation behaviour of poly (butylene terephthalate) mouldings
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Chisato Nonomura, Daisuke Watanabe, Atsushi Yokoyama, Toshiro Yamada, Asami Nakai, Akio Tange, Katsuhisa Yamashita, and Katsuya Ito
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Work (thermodynamics) ,Materials science ,Polymers and Plastics ,General Chemical Engineering ,Numerical analysis ,Ultimate tensile strength ,Materials Chemistry ,Ceramics and Composites ,Strain rate ,Composite material ,Deformation (engineering) ,Finite element method ,Necking - Abstract
This paper examines the factors controlling the formation and propagation of a neck in poly (butylene terephthalate) (PBT) mouldings under tensile loading. Tensile tests were used to investigate the load–displacement and deformation behaviour of PBT and the accompanying changes in surface temperature. In parallel with this experimental study, a numerical model was developed for the deformation of PBT mouldings and neck formation under tensile loading analysed using finite element analysis (FEA). The calculated numerical results were compared with the experimental data. This work has shown that formation does not occur in PBT immediately after the yield point. Instead, plastic deformation first progresses homogeneously through the testpiece. Neck formation and propagation, accompanied by a rise in temperature, then follow. The load–displacement behaviour calculated using FEA could be approximated to the experimental data by adapting an elastic–plastic model at a stable temperature to the necking be...
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- 2001
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17. Laboratory Correlates of Chemoimmunotherapy with Low-Dose Recombinant Interleukin-2 and Mitomycin C in Patients with Advanced Carcinoma
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Nobuya Karimine, Shigeru Nanbara, Tsuyoshi Akiyoshi, Kiyoshi Takamuku, Hiroaki Ueo, Daisuke Watanabe, Tsukasa Asoh, Ryoji Abe, Shinya Arinaga, and Hiroshi Inoue
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Adult ,Cytotoxicity, Immunologic ,Male ,Cancer Research ,Mitomycin ,Lymphocyte ,Pharmacology ,Leukocyte Count ,Predictive Value of Tests ,Chemoimmunotherapy ,Neoplasms ,White blood cell ,Cell Adhesion ,medicine ,Humans ,Cytotoxic T cell ,Killer Cells, Lymphokine-Activated ,Aged ,Dose-Response Relationship, Drug ,business.industry ,Mitomycin C ,Cancer ,General Medicine ,Middle Aged ,Eosinophil ,medicine.disease ,Combined Modality Therapy ,Recombinant Proteins ,Killer Cells, Natural ,Regimen ,Phenotype ,medicine.anatomical_structure ,Oncology ,Immunology ,Leukocytes, Mononuclear ,Cytokines ,Interleukin-2 ,Female ,Immunotherapy ,business - Abstract
Based on our clinical findings that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells was remarkably augmented after mitomycin C (MMC) administration, we designed a treatment regimen that consisted of MMC 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 (IL-2) 700 U/m2, i.v. every 12 hr from day 4 through day 8. Of 29 patients with advanced carcinoma treated with this regimen, 10 had a partial response (PR) and 4 had a minor response. The correlation of hematological and immunological changes associated with this treatment with the antitumor response to this therapy was investigated. Pretreatment values of total white blood cell and lymphocyte counts, and the level of increase of eosinophil counts in responder patients who showed a PR, were significantly greater than those in nonresponder patients. However, there was no correlation between clinical response and cytotoxic activities of peripheral blood mononuclear (PBM) cells, including NK and LAK activity, and the ability to generate LAK cells after the treatment. The capacity of adherent cells in PBM to produce IL-1-beta was increased after the treatment in both responders and nonresponders, whereas IL-1-alpha production was not increased. In addition, a significant increase in the ability to produce TNF-alpha was observed only in responders, indicating the correlation of TNF-alpha production with clinical response to this therapy. Since these correlations had been reported in the previous studies using IL-2, the present results suggested that the therapeutic effectiveness of this therapy against advanced carcinoma, is due to IL-2 probably augmented by its combination with MMC. In addition, these parameters might be predictive of therapeutic efficacy of this treatment.
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- 1994
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18. Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood–brain barrier primary triple coculture model
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Taro Takemura, Robert A. Yokel, Anliang Shao, Nobutaka Hanagata, Cuiping Zhang, Liming Xu, Masami Niwa, Daisuke Watanabe, Xiang Cheng, and Mo Dan
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Cell Membrane Permeability ,Metal Nanoparticles ,Pharmaceutical Science ,Silver nanoparticle ,International Journal of Nanomedicine ,Drug Discovery ,Cells, Cultured ,health care economics and organizations ,Original Research ,antioxidant defense ,Ag nanoparticles ,Tight junction ,Brain ,General Medicine ,medicine.anatomical_structure ,Blood-Brain Barrier ,Toxicity ,cardiovascular system ,Signal transduction ,Signal Transduction ,Astrocyte ,inorganic chemicals ,Silver ,global gene expression analysis ,Biophysics ,Bioengineering ,Nanotechnology ,Real-Time Polymerase Chain Reaction ,Blood–brain barrier ,Models, Biological ,Tight Junctions ,Biomaterials ,Microscopy, Electron, Transmission ,medicine ,Animals ,business.industry ,Gene Expression Profiling ,Organic Chemistry ,astrocytes ,technology, industry, and agriculture ,Neurotoxicity ,Biological Transport ,medicine.disease ,BBB model ,Rat blood ,Coculture Techniques ,Rats ,nervous system ,Endothelium, Vascular ,business - Abstract
Liming Xu,1,2,* Mo Dan,1,* Anliang Shao,1 Xiang Cheng,1,3 Cuiping Zhang,4 Robert A Yokel,5 Taro Takemura,6 Nobutaka Hanagata,6 Masami Niwa,7,8 Daisuke Watanabe7,81National Institutes for Food and Drug Control, No 2, Temple of Heaven, Beijing, 2School of Information and Engineering, Wenzhou Medical University, Wenzhou, 3School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 4Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China; 5College of Pharmacy, University of Kentucky, Lexington, KY, USA; 6Nanotechnology Innovation Station for Nanoscale Science and Technology, National Institute for Materials Science, Tsukuba, Ibaraki, 7Department of Pharmacology, Nagasaki University, 8BBB Laboratory, PharmaCo-Cell Company, Ltd., Nagasaki, Japan*These authors contributed equally to this workBackground: Silver nanoparticles (Ag-NPs) can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood–brain barrier (BBB) and the underlying mechanism(s) of action on the BBB and the brain are not well understood.Method: To investigate Ag-NP suspension (Ag-NPS)-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM). Global gene expression of astrocytes was measured using a DNA microarray.Results: A triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values >200Ω·cm2. After Ag-NPS exposure for 24hours, the BBB permeability was significantly increased and expression of the tight junction (TJ) protein ZO-1 was decreased. Discontinuous TJs were also observed between microvascular endothelial cells. After Ag-NPS exposure, severe mitochondrial shrinkage, vacuolations, endoplasmic reticulum expansion, and Ag-NPs were observed in astrocytes by TEM. Global gene expression analysis showed that three genes were upregulated and 20 genes were downregulated in astrocytes treated with Ag-NPS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the 23 genes were associated with metabolic processes, biosynthetic processes, response to stimuli, cell death, the MAPK pathway, and so on. No GO term and KEGG pathways were changed in the released-ion or polystyrene-NP groups. Ag-NPS inhibited the antioxidant defense of the astrocytes by increasing thioredoxin interacting protein, which inhibits the Trx system, and decreasing Nr4a1 and Dusp1. Meanwhile, Ag-NPS induced inflammation and apoptosis through modulation of the MAPK pathway or B-cell lymphoma-2 expression or mTOR activity in astrocytes.Conclusion: These results draw our attention to the importance of Ag-NP-induced toxicity on the neurovascular unit and provide a better understanding of its toxicological mechanisms on astrocytes.Keywords: Ag nanoparticles, astrocytes, BBB model, global gene expression analysis, antioxidant defense
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- 2015
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