Mitsuru Akashi

Osaka University, Suika, Ōsaka, Japan

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Publications (588)2125.41 Total impact

  • Fumiaki Shima, Takami Akagi, Mitsuru Akashi
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    ABSTRACT: The new generation vaccines are safe but poorly immunogenic, and thus they require the use of adjuvants, and adjuvants which can control the balance and induction level of cellular and humoral immunities are urgently required for the treatment and/or protection of infectious diseases and cancers. Although, there have no adjuvants which can achieve these requirements. In this study, amphiphilic poly(γ-glutamic acid) (γ-PGA) with various kinds of hydrophobic amino acid ethyl esters (AAE), was synthesized (γ-PGA-AAE) and prepared antigen-encapsulated nanoparticles (NPs). γ-PGA-graft-Leu (γ-PGA-Leu, Leu; leucine ethyl ester), γ-PGA-graft-Phe (γ-PGA-Phe, Phe; phenylalanine ethyl ester), and γ-PGA-graft-Trp (γ-PGA-Trp, Trp; tryptophan ethyl ester) formed monodispersed NPs that encapsulated ovalbumin (OVA). The type and the induction level of the antigen-specific cellular and humoral immunities could be controlled by the kinds of hydrophobic segments and vaccine formulation (encapsulation or mixture). When OVA was encapsulated into NPs, the cellular immunity was dominantly induced, while humoral immunity was dominant when OVA was mixed with NPs. These results are a first report that demonstrated the balance and induction level of cellular and humoral immunities could be controlled by modifying compositions of NPs and vaccine formulation. Our results suggest that γ-PGA-AAE NPs can provide safe and efficient nanoparticle-based vaccine adjuvants, and provide guidelines in the rational design of amphiphilic polymers as vaccine adjuvants which can control the balance of immune responses.
    Bioconjugate Chemistry 04/2015; DOI:10.1021/acs.bioconjchem.5b00106 · 4.82 Impact Factor
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    ABSTRACT: Urethane-crosslinked β-cyclodextrin polymers are prepared by crosslinking heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) with various diisocyanate linkers, such as 4,4′-methylenebis(phenyl isocyanate) (MDI), 1,4-phenylene diisocyanate (PDI) and hexamethylene diisocyanate (HMDI), in DMF. Among these polymers, MDI- and PDI-crosslinked polymers have high adsorption capabilities toward polychlorobiphenyls (PCBs), such as tetra, penta and hexachlorobiphenyl, in isooctane. Toward hexachlorobiphenyl in insulating oil, the adsorption capability of the MDI-crosslinked polymer increases with the adsorption temperature. In addition, using acetone as a washing solvent gives the highest recovery percentage of the PCB from the PCB-adsorbed polymer.
    Polymer Journal 04/2015; DOI:10.1038/pj.2015.13 · 1.55 Impact Factor
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    ABSTRACT: The androgen testosterone is less expensive than bone morphogenetic proteins and has been shown to effectively repair bone fractures. However, testosterone is lipophilic and insoluble in water, making it difficult to load into hydrogels, which are common drug carriers. In this study, we prepared a novel oil gel composed of poly(L-lactide) and a poly(trimethylene carbonate) derivative and studied the release of testosterone from the gel. Dimethyl sulfoxide and dimethyl carbonate, which are organic solvents with relatively low toxicities, were used as dispersion media. The oil gel in dimethyl sulfoxide released testosterone faster than that in dimethyl carbonate. In addition, the dimethyl carbonate oil gel was vacuum-dried to reduce the gel porosity and thus slow testosterone release. Therefore, oil gel is a promising substrate for lipophilic drugs, including testosterone.
    Polymer Journal 04/2015; DOI:10.1038/pj.2015.17 · 1.55 Impact Factor
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    ABSTRACT: We developed a human skin equivalent (HSE) containing blood and lymph-like capillary networks using a cell coating technique, which is a rapid fabrication technology of three-dimensional cellular constructs by cell surface coating using layer-by-layer assembled nanofilms of extracellular matrices. The thickness of dermis consisting of normal human dermal fibroblasts was easily controlled from approximately 5 to 100 µm by altering the seeded cell number. Keratinocytes as a major cell population showed homogeneous differentiation on the surface of the dermis by lifting to air-liquid interface. Histological analysis revealed four distinct layers such as basal layer, spinous layer, granular layer and cornified cell layer in the epidermis. Interestingly, the measurement of trans-epithelial electrical resistance (TEER) indicated prolongation of the attainment time for maximum value by increasing the number of the dermal fibroblasts, and the HSEs with six-layers of dermis revealed the longest period maintaining over 500 Ω·cm(2) of TEER. The co-sandwich culture of human umbilical vein endothelial cells and normal human dermal lymphatic microvascular endothelial cells within eight-layered dermis showed in vitro co-network formation of individual blood and lymph-like capillaries inside the dermis. This is the first report for homogeneous full-thickness HSEs with blood and lymph capillary networks, which will be useful for biomedical and pharmaceutical applications. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Journal of Biomedical Materials Research Part A 04/2015; DOI:10.1002/jbm.a.35473 · 2.83 Impact Factor
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    ABSTRACT: Development of effective and simple vaccine preparation is desired for prophylaxis and treatment of a variety of infectious diseases and cancers. We have created novel polyion complex (PIC) nanoparticle (NPs) composed of amphiphilic anionic biodegradable poly(γ-glutamic acid) (γ-PGA) and cationic polymers as a vaccine adjuvant. PIC NPs can be prepared by mixing γ-PGA-graft-l-phenylalanine ethylester (γ-PGA-Phe) polymer with cationic polymer in phosphate buffered saline. We examined the efficacy of PIC NPs for their antigen delivery and immunostimulatory activity in vitro and in vivo. PIC NPs enhanced the uptake of ovalbumin (OVA) by dendritic cells (DCs) and subsequently induced DC maturation. The immunization of mice with OVA-carrying PIC NPs could induce potent and antigen-specific cellular and humoral immunity. Since PIC NPs can be created with water-soluble anionic γ-PGA-Phe and a cationic polymer by simple mixing in the absence of any organic solvents, PIC NPs may have potential as a novel candidate for an effective antigen carrier and vaccine adjuvant. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Clinical and vaccine Immunology: CVI 03/2015; 22(5). DOI:10.1128/CVI.00080-15 · 2.37 Impact Factor
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    ABSTRACT: Cyclic l-lactic acid octamer (l-COLA-8) shows a unique complexing capability towards alkali and alkali earth metal cations in acetonitrile-d3/chloroform-d (9/1). The valence of the cation affects the stoichiometry of the complexes between l-COLA-8 and the cation; l-COLA-8 forms a 2:1 complex with alkali metal cations, but forms a 1:1 complex with alkali earth metal cations. Additionally, l-COLA-8 shows a binding selectivity for Rb+ and Ba2+, which have a diameter about 3 Å.
    Tetrahedron Letters 03/2015; 56(13). DOI:10.1016/j.tetlet.2015.02.037 · 2.39 Impact Factor
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    ABSTRACT: Front Cover: Heparin-based ECM nanofilms formed on living cells by layer-by-layer assembly induce cell-cell crosslinking through bio-molecular recognition between highly-sulfated polymers and membrane proteins. Cell aggregates display network structures of cells and the cell-cell crosslinking process leads to in vitro 3D-tissue construction with rich glycosaminoglycan. The cellular assembly technique presented by M. Akashi and co-workers on page 312 has potential for tissue engineering and intercellular signalling assay. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Macromolecular Bioscience 03/2015; 15(3):293. DOI:10.1002/mabi.201570009 · 3.65 Impact Factor
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    ABSTRACT: Surface polyion complex (sPIC) gels were prepared with a nonionic hydrogel interior core, composed of poly(N-vinylformamide and poly(N-vinylacetamide), and a chemically bounded polyion complex layer on the outer surface, composed of poly(vinylamine) and poly(acrylic acid). The gels were investigated as controlled drug release models based on electrostatic interactions depending on pH. Methylene blue and allura red were employed as cationic and anionic drug models, respectively, and resulted in the selective adsorption depending on pH conditions. Monovalent and multivalent anionic drug models, allura red and 1,3,6-naphthalenetrisulfonate were observed for their releasing behavior from the sPIC gel. The results indicated that the multivalent anionic drug effectively controlled release depending on pH conditions. We further investigated sPIC gels regarding their ability to control the release of ionic molecules as a function of pH-driven changes in electrostatic interactions. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42081.
    Journal of Applied Polymer Science 03/2015; 132(24). DOI:10.1002/app.42081 · 1.64 Impact Factor
  • Chun-Yen Liu, Michiya Matsusaki, Mitsuru Akashi
    Polymer Journal 02/2015; 47(5). DOI:10.1038/pj.2015.2 · 1.55 Impact Factor
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    ABSTRACT: Hydroxyapatite agarose composite gel (HAp gel) is a radiolucent and absorbable bone–graft material that differs from hydroxyapatite ceramic; it is more rapidly absorbed and replaced by new bone than existing materials. This study examined the usefulness of HAp gel in the repair of alveolar bone defects due to cleft lip and palate.
    02/2015; DOI:10.1016/j.ajoms.2015.01.003
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    ABSTRACT: Functional 3D-engineered tissues are successfully harvested from a substrate using stimuli-responsive hydrogel films with dynamic nano-interface. The dynamic wettability control at the interfaces allows cellular detachment, leading to tissue harvesting without serious damage and remaining polymers. This method can be applied to various types of organs and used for tissue transplantation in regenerative medicine. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Advanced Healthcare Materials 02/2015; DOI:10.1002/adhm.201500065 · 4.88 Impact Factor
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    ABSTRACT: The aim of the present research was to study the thermal stability of ferulic acid after coupling onto chitosan, and the possibility of using ferulic acid-coupled chitosan (FA-CTS) as an antioxidant for biodegradable active packaging film. FA-CTS was incorporated into biodegradable film via a two-step process, i.e. compounding extrusion at temperatures up to 150°C followed by blown film extrusion at temperatures up to 175°C. Although incorporation of FA-CTS with a content of 0.02-0.16% (w/w) caused decreased water vapor barrier property and reduced extensibility, the biodegradable films possessed improved oxygen barrier property and antioxidant activity. Radical scavenging activity and reducing power of film containing FA-CTS were higher than those of film containing naked ferulic acid, by about 254% and 94%, respectively. Tensile strength and rigidity of the films were not significantly affected by the addition of FA-CTS with a content of 0.02-0.08% (w/w). The above results suggested that FA-CTS could potentially be used as an antioxidant for active packaging film. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Carbohydrate Polymers 01/2015; 115:744-51. DOI:10.1016/j.carbpol.2014.06.074 · 3.92 Impact Factor
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    ABSTRACT: Although many rhodamine based fluorescence sensors were reported to detect metal ions with high sensitivity and selectivity, there are very few reports available to study the mechanisms of detection and the interaction between probe and metal ions. This paper aims to detect ferric ions by novel fluorescence chemosensors and study the mechanisms in detail. A novel probe AD-MAH-RhB was designed and synthesized from rhodamine B (RhB), adamantyl (AD), ethylene diamine and maleic anhydride (MAH). AD-MAH-RhB could detect Fe(3+) in aqueous solutions. The mechanism was explored by the HSAB principle, FTIR and mass spectra. The results suggested that Fe(3+) bound with amine and oxygen atoms in AD-MAH-RhB to form a complex composed of a 2 : 1 stoichiometry of Fe(3+) and the probe. Moreover, computational simulations were employed to further investigate the detection mechanism. The calculated results showed that Fe(3+) could conjugate with AD-MAH-RhB probe to form a stable complex, which was induced by synergetic effects of the suitable space and distance of van der Waals forces. However, Hg(2+) was found to disturb this detection and form a complex with 1 : 2 stoichiometry of Hg(2+) and AD-MAH-RhB. Then, another probe, β-cyclodextrin modified polymaleic anhydride (PMAH-CD) including AD-MAH-RhB (PMAH-CD/AD-MAH-RhB) was fabricated by inclusion interaction between CD and AD. PMAH-CD@AD-MAH-RhB showed high selectivity and sensitivity to Fe(3+) in the aqueous solution by eliminating the interruption of Hg(2+) possibly due to the high hydrogen interaction among the probes to inhibit the stable form complex with Hg(2+).
    The Analyst 01/2015; DOI:10.1039/c4an01991a · 3.91 Impact Factor
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    ABSTRACT: When bio-molecular recognition between nanofilms and proteins occurs on cell surfaces, rapid cellular assembly takes place. Cells coated with layer-by-layer nanofilms composed of fibronectin and heparin form aggregates after centrifugation and nanofilms induce attractive forces between cells through bio-molecular recognition between membrane proteins and heparin. Cell aggregates display network structures of cells as seen in colloidal gels with high viscosity. Cell—cell crosslinking allows for the construction of 3D-tissues with rich glycosaminoglycan. This cell—cell crosslinking process that uses a layer-by-layer technique has enormous potential for in vitro tissue applications in regenerative medicine and cell signaling assays.
    Macromolecular Bioscience 01/2015; 15(3). DOI:10.1002/mabi.201400415 · 3.65 Impact Factor
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    ABSTRACT: Caco-2, human colon carcinoma cell line, has been widely used as a model system for intestinal epithelial permeability because Caco-2 cells express tight-junctions, microvilli, and a number of enzymes and transporters characteristic of enterocytes. However, the functional differentiation and polarization of Caco-2 cells to express sufficient tight-junctions (a barrier) usually takes over 21 days in culture. This may be due to the cell culture environment, for example inflammation induced by plastic petri dishes. Three-dimensional (3D) sufficient cell microenvironments similar to in vivo natural conditions (proteins and cells), will promote rapid differentiation and higher functional expression of tight junctions. Herein we report for the first time an enhancement in tight-junction formation by 3D-cultures of Caco-2 cells on monolayered (1L) and eight layered (8L) normal human dermal fibroblasts (NHDF). Trans epithelial electric resistance (TEER) of Caco-2 cells was enhanced in the 3D-cultures, especially 8L-NHDF tissues, depending on culture times and only 10 days was enough to reach the same TEER value of Caco-2 monolayers after a 21 day incubation. Relative mRNA expression of tight-junction proteins of Caco-2 cells on 3D-cultures showed higher values than those in monolayer structures. Transporter gene expression patterns of Caco-2 cells on 3D-constructs were almost the same as those of Caco-2 monolayers, suggesting that there was no effect of 3D-cultures on transporter protein expression. The expression correlation between carboxylesterase 1 and 2 in 3D-cultures represented similar trends with human small intestines. The results of this study clearly represent a valuable application of 3D-Caco-2 tissues for pharmaceutical applications. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 01/2015; 457(3). DOI:10.1016/j.bbrc.2014.12.118 · 2.28 Impact Factor
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    ABSTRACT: The porous isotactic (it-) poly(methyl methacrylate) (PMMA) thin film, which is prepared by layer-by-layer (LbL) assembly with it-PMMA and syndiotactic (st-) poly(methacrylic acid) (PMAA) on a substrate and the successive extraction of st-PMAA, was investigated on the aspect of the mechanism of stereoregular template polymerization, inspired by the idea “molecular technology”. The porous it-PMMA film was analyzed with XRD and FT-IR spectra, after the treatment with acetonitrile or a heating process, resulting in partially crystallized it-PMMA, which gave low efficiency of stereoregular template polymerization. The template polymerization under various conditions was also tested, using methacrylamide, methyl methacrylate, and acrylic acid as methacrylic acid derivatives. Furthermore, st-PMAAs with different syndiotacticity were employed to prepare the porous it-PMMA film after LbL film preparation, resulting in low yields and stereoregularity on template polymerization. The results imply that perfect polymer-polymer interaction is essential to achieve precise polymerization in stereoregular template polymerization.
    Kōbunshi rombun shū 01/2015; DOI:10.1295/koron.2014-0090 · 0.22 Impact Factor
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    ABSTRACT: Monolayers of endothelial cells (1L-ECs) have been generally used as in vitro vascular wall models to study the vascular mechanisms and transport of substances. However, these two-dimensional (2D-) system cannot represent the properties of native vascular wall which has 3D-structure and composed of not only ECs, but also smooth muscle cells (SMCs) and other surround tissues. Here in, five-layered (5L) 3D-arterial wall models (5L-AWMs) composed of EC monolayer and 4-layered SMCs were constructed by hierarchical cell manipulation. We applied the 5L-AWMs to evaluate their barrier function and permeability to nano-materials in order to analyze drug, or drug nanocarrier permeability to the blood vessel in vitro. Barrier property of the 3D-AWMs was confirm by Zonula occludens (ZO-1) staining and their transendothelial electrical resistance (TEER), which was comparable to 1L-ECs, while the SMCs showed close to zero. The effect of substance size to permeability across the 5L-AWMs was clearly observed from dextrans with various molecular weights, which agreed well with phenomena of the in vivo blood vessels. Importantly, transport of nano-materials could be observed across the depth of 5L-AWMs, suggesting the advantage of 3D-AWMs over general 2D-systems. By using this system, we evaluate the transport of 35 nm phenylalanine-modified poly(γ-Glutamic Acid) nanoparticles (γ-PGA-Phe NPs) as a candidate of biodegradable drug carrier. Interestingly, despite of having comparable size to dextran-2000k (28 nm), the γ-PGA-Phe NPs distinctly showed approximately 20 times faster transport across the 5L-AWMs, suggesting the effect of substance intrinsic properties to the transport. This in vitro evaluation system using the 3D-AWMs is therefore useful for the design and development of nano-drug carriers for treatment of vascular diseases, such as atherosclerosis. Copyright © 2014. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 12/2014; 456(1). DOI:10.1016/j.bbrc.2014.11.094 · 2.28 Impact Factor
  • Hiroharu Ajiro, Kazuya Takemura, Mitsuru Akashi
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    ABSTRACT: The surface polyion complex gel (sPIC gel), which possesses chemically bonded nonionic gel moiety, was designed using N-vinylacetamide (NVA), N-vinylforamide (NVF), and vinyl phosphonic acid (VPA). Taking advantage of the property of NVF as vinylamine (VAm) precursor, the cationic moiety was introduced only onto the surface of poly(NVA-co-NVF), producing surface hydrolyzed poly(NVA-co-NVF-co-VAm), and the successive polymerization of VPA inside the gel successfully produced sPIC gel. The swelling ratio of the sPIC gel was investigated under various pH conditions, and compared with that of the fully polyion complex gel (PIC gel), using totally hydrolyzed poly(NVA-co-VAm). The swelling ratio of sPIC gel ranged between 14 and 25, while that of the PIC gel ranged between 2 and 5. The anionic compound, AR, showed a sustained release from sPIC gel at pH 2, due to the electrostatic interactions. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014
    Journal of Polymer Science Part A Polymer Chemistry 12/2014; 53(4). DOI:10.1002/pola.27476 · 3.54 Impact Factor
  • Hiroharu Ajiro, Tatsuaki Ueyama, Mitsuru Akashi
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    ABSTRACT: The radical polymerization of methacrylic acid (MAA) at 0, 20, 40, and 70 °C was achieved in porous isotactic (it-) poly(methyl methacrylate) (PMMA) films on quartz crystal microbalance (QCM) substrates, which were prepared by layer-by-layer assembled stereocomplex films of it-PMMA and syndiotactic (st-) poly(methacrylic acid) (PMAA), followed by the subsequent extraction of st-PMAA. The MAA polymerization yields increased from 35 to 75%, as the polymerization temperature increased from 0 to 70 °C. Furthermore, infrared spectroscopy revealed that a higher polymerization temperature is necessary to form it-PMMA/st-PMAA stereocomplexes via stereoregular polymerization manner that resemble native it-PMMA/st-PMAA stereocomplexes. X-ray diffraction pattern of porous it-PMMA were also investigated for reaction fields. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014
    Journal of Polymer Science Part A Polymer Chemistry 11/2014; 52(21). DOI:10.1002/pola.27350 · 3.54 Impact Factor
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    ABSTRACT: We described an assembly technique and perfusion culture system for constructing artery tissue models. This technique differed from previous studies in that it does not require a solid biodegradable scaffold; therefore, using sheet-like tissues, this technique allowed the facile fabrication of tubular tissues can be used as model. The fabricated artery tissue models had a multilayer structure. The assembly technique and perfusion culture system were applicable to many different sizes of fabricated arteries. The shape of the fabricated artery tissue models was maintained by the perfusion culture system; furthermore, the system reproduced the in vivo environment and allowed mechanical stimulation of the arteries. The multilayer structure of the artery tissue model was observed using fluorescent dyes. The equivalent Young's modulus was measured by applying internal pressure to the multilayer tubular tissues. The aim of this study was to determine whether fabricated artery tissue models maintained their mechanical properties with developing. We demonstrated both the rapid fabrication of multilayer tubular tissues that can be used as model arteries and the measurement of their equivalent Young's modulus in a suitable perfusion culture environment.
    Biomicrofluidics 11/2014; 8(6):064113. DOI:10.1063/1.4903210 · 3.77 Impact Factor

Publication Stats

8k Citations
2,125.41 Total Impact Points


  • 2003–2015
    • Osaka University
      • • Division of Applied Chemistry
      • • Graduate School of Engineering
      Suika, Ōsaka, Japan
  • 2006–2013
    • Japan Science and Technology Agency (JST)
      Edo, Tōkyō, Japan
    • Nanjing University of Science and Technology
      Nan-ching, Jiangsu Sheng, China
  • 2012
    • RWTH Aachen University
      Aachen, North Rhine-Westphalia, Germany
  • 1984–2010
    • Kagoshima University
      • • Graduate School of Medical and Dental Sciences
      • • Center for Educational Research and Development
      • • Graduate School of Science and Engineering
      • • Faculty of Engineering
      • • Division of Human Retroviruses
      Kagoshima-shi, Kagoshima-ken, Japan
  • 2009
    • Jiangnan University
      • School of Chemical and Material Engineering
      Wuxi, Jiangsu Sheng, China
  • 2005–2007
    • Yangtze University
      • School of Chemical and Material Engineering
      Hu-pei-ts’un, Shanxi Sheng, China
    • Kyoto Institute of Technology
      Kioto, Kyōto, Japan
    • Osaka Institute of Technology
      • Department of Applied Chemistry
      Ōsaka, Ōsaka, Japan
  • 2004
    • Chulalongkorn University
      • Petroleum and Petrochemical College
      Krung Thep, Bangkok, Thailand
  • 1997
    • Slovak Academy of Sciences
      • Polymer Institute
      Presburg, Bratislavský, Slovakia
  • 1991
    • University of Tsukuba
      Tsukuba, Ibaraki, Japan