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Development of molecular mechanism and therapy of Diamond-Blackfan anemia

Research Project

Project/Area Number 23591554
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNippon Medical School

Principal Investigator

KOICHI Miyake  日本医科大学, 医学部, 准教授 (90267211)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsリボゾーム蛋白 / 貧血 / 先天異常 / 先天性貧血 / siRNA / Diamond-Blackfan anemia / 遺伝子治療
Research Abstract

Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia in which 25% of the patients have a mutation in the ribosomal protein S19 gene. Recently, it was reported that other ribosomal proteins (RPL5, RPL11, RPS24, RPS17) were also mutated in DBA patients. We constructed lentiviral vector expressing siRNA against RPL5, RPL11, RPS24, and RPS17 to analyze the molecular mechanism of DBA. We established cell line model of DBA after transduction with these lentiviral vector. To develop DBA model mouse, first, we generated KRAB (Kruppel-associated box) gene transgenic mouse. Using this mouse, we have a plan to make a tetracycline inducible DBA model mouse.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (52 results)

All 2014 2013 2012 2011

All Journal Article (25 results) (of which Peer Reviewed: 25 results) Presentation (23 results) Book (4 results)

  • [Journal Article] siRNA Knockdown of Tissue Inhibitor of Metalloproteinase-1 in Keloid Fibroblasts Leads to Degradation of Collagen Type I2014

    • Author(s)
      Aoki M, Miyake K, Ogawa R, Dohi T, Akaishi S, Hyakusoku H, Shimada T
    • Journal Title

      J Invest Dermatol

      Volume: 134 Pages: 818-826

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] miR-7a alleviates the maintenance of neuropathic pain through regulation of neuronal excitability2014

    • Author(s)
      Sakai A, Saitow F, Miyake N, Miyake K, Shimada T, Suzuki H
    • Journal Title

      Brain

      Volume: 136 Pages: 2738-2750

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutant Ataxin-3 with an Abnormally Expanded Polyglutamine Chain Disrupts Dendritic Development and Metabotropic Glutamate Receptor Signaling in Mouse Cerebellar Purkinje Cells2014

    • Author(s)
      Konno A, Shuvaev AN, Miyake N, Miyake K, Iizuka A, Matsuura S, Huda F, Nakamura K, Yanagi S, Shimada T, Hirai H
    • Journal Title

      Cerebellum

      Volume: 13 Pages: 29-41

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclical mechanical stretch enhances degranulation and IL-4 secretion in RBL-2H3 mast cells2014

    • Author(s)
      komiyama H, Miyake K, Asai K, Mizuno K, Shimada T
    • Journal Title

      Cell Biochemistry & Function

      Volume: 32 Pages: 70-76

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclical mechanical stretch enhances degranulation and IL-4 secretion in RBL-2H3 mast cells2014

    • Author(s)
      Komiyama H, Miyake K, Asai K, Mizuno K, Shimada T.
    • Journal Title

      Cell Biochem Funct.

      Volume: 32 Issue: 1 Pages: 70-76

    • DOI

      10.1002/cbf.2973

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutant ataxin-3 with an abnormally expanded polyglutamine chain disrupts dendritic development and metabotropic glutamate receptor signaling in mouse cerebellar purkinje cells2014

    • Author(s)
      Konno A, Shuvaev AN, Miyake N, Miyake K, Iizuka A, Matsuura S, Huda F, Nakamura K, Yanagi S, Shimada T, Hirai H.
    • Journal Title

      Cerebellum

      Volume: 13 Issue: 1 Pages: 29-41

    • DOI

      10.1007/s12311-013-0516-5

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] siRNA Knockdown of Tissue Inhibitor of Metalloproteinase-1 in Keloid Fibroblasts Leads to Degradation of Collagen Type I2014

    • Author(s)
      Aoki M, Miyake K, Ogawa R, Dohi T, Akaishi S, Hyakusoku H, Shimada T.
    • Journal Title

      J Invest Dermatol.

      Volume: 134 Issue: 3 Pages: 818-826

    • DOI

      10.1038/jid.2013.396

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct Comparison of Administration Routes for AAV8-mediated Ocular Gene Therapy2013

    • Author(s)
      Igarashi T, Miyake K, Asakawa N, Miyake N, Shimada T, Takahashi H.
    • Journal Title

      Curr Eye Res

      Volume: 38 Pages: 569-577

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Team-based Learning Using an Audience Response System : A Possible New Strategy for Interactive Medical Education2013

    • Author(s)
      Fujikura T, Takeshita T, Homma H, Adachi K, Miyake K, Kudo M, Takizawa T, Nagayama H, Hirakawa K
    • Journal Title

      J Nippon Med Sch

      Volume: 80 Pages: 63-69

    • NAID

      130004147207

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Direct comparison of administration routes for AAV8-mediated ocular gene therapy2013

    • Author(s)
      Igarashi T, Miyake K, Asakawa N, Miyake N, Shimada T, Takahashi H.
    • Journal Title

      Curr Eye Res.

      Volume: 38 Issue: 5 Pages: 569-577

    • DOI

      10.3109/02713683.2013.779720

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of survivin in acute lung injury: Epithelial cells of mice and humans2013

    • Author(s)
      Terasaki Y, Terasaki M, Urushiyama H, Nagasaka S,Kungi S, et al.
    • Journal Title

      Lab Invest

      Volume: 93 Issue: 10 Pages: 1147

    • DOI

      10.1038/labinvest.2013.103

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-7a alleviates the maintenance of neuropathic pain through regulation of neuronal excitability2013

    • Author(s)
      Sakai A, Saitow F, Miyake N, Miyake K, Shimada T, Suzuki H.
    • Journal Title

      Brain

      Volume: 136 Issue: 9 Pages: 2738-2750

    • DOI

      10.1093/brain/awt191

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serotype-independent method of recombinant adeno-associated virus (AAV) vector production and purification2012

    • Author(s)
      Miyake K, Miyake N, Yamazaki Y, Shimada T, Hirai Y.
    • Journal Title

      J Nippon Med Sch

      Volume: 79 Pages: 394-402

    • NAID

      130004057397

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of gata4, mef2c, and tbx52012

    • Author(s)
      Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T, Umei T, Wada R, Katsumata Y, Kaneda R, Nakade K, Kurihara C, Obata Y, Miyake K, Fukuda K, Ieda M.
    • Journal Title

      Circ Res

      Volume: 111 Pages: 1147-1156

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful gene therapy in utero for lethal murine hypophosphatasia2012

    • Author(s)
      Sugano H, Matsumoto T, Miyake K, Watanabe A, Iijima O, Migita M, Narisawa S, Millán JL, Fukunaga Y, Shimada T.
    • Journal Title

      Hum Gene Ther

      Volume: 23 Pages: 399-406

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] AAV-8 vector expressing IL-24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice2012

    • Author(s)
      Tamai H, Miyake K, Yamaguchi H Takatori M, Dan K, Inokuchi K, Shimada T.
    • Journal Title

      Blood

      Volume: 119 Pages: 64-71

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serotype-independent Method of Recombinant Adeno-associated. Virus (AAV) Vector Production and Purification2012

    • Author(s)
      Miyake K, Miyake N, Yamazaki Y, Shimada T, Hirai Y
    • Journal Title

      J Nippon Med Sch

      Volume: 79 Pages: 394-402

    • NAID

      130004057397

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Induction of Cardiomyocyte-like Cells in Infarct Hearts by Gene Transfer of Gata4, Mef2c, and Tbx52012

    • Author(s)
      Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T, Umei T, Wada R, Katsumata Y, Kaneda R, Nakade K, Kurihara C, Obata Y, Miyake K, Fukuda K, Ieda M
    • Journal Title

      Circulation research

      Volume: 111 Issue: 9 Pages: 1147-56

    • DOI

      10.1161/circresaha.112.271148

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] AAV-8 vector expressing IL-24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice.2012

    • Author(s)
      Tamai, H.
    • Journal Title

      Blood

      Volume: 119 Issue: 1 Pages: 64-71

    • DOI

      10.1182/blood-2011-05-354050

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Resistance of MLL-AFF1-positive acute lymphoblastic leukemia to tumor necrosis factor-alpha is mediated by S100A6 up-regulation2011

    • Author(s)
      Tamai H, Miyake K, Yamaguchi H Takatori M, Dan K, Inokuchi K, Shimada T.
    • Journal Title

      Blood Cancer Journal

      Volume: 1

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia2011

    • Author(s)
      Wakita S, Yamaguchi H, Miyake K, Mitamura Y, Kosaka F, Dan K, Inokuchi K.
    • Journal Title

      Leukemia

      Volume: 25 Pages: 1423-32

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Parkin-mediated protection of dopaminergic neurons in a chronic MPTP-minipump mouse model of Parkinson disease2011

    • Author(s)
      Yasuda T, Hayakawa H, Nihira T, Ren YR, Nakata Y, Nagai M, Hattori N, Miyake K, Takada M, Shimada T, Mizuno Y, Mochizuki H.
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 70 Pages: 686-97

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activated K-Ras protein accelerates human MLL/AF4-induced leukemo-lymphomogenicity in a transgenic mouse model2011

    • Author(s)
      Tamai H, Miyake K, Takatori M, Miyake N Yamaguchi H, Dan K, Shimada T, Inokuchi K.
    • Journal Title

      Leukemia

      Volume: 25 Pages: 888-91

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Direct comparison of four adeno-associated virus serotypes in mediating the production of antiangiogenic proteins in mouse muscle2011

    • Author(s)
      Isotani M, Miyake K, Miyake N, Hirai Y, Shimada T.
    • Journal Title

      Cancer Invest

      Volume: 29(5) Pages: 353-359

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Direct Comparison of Four Adeno-Associated Virus Serotypes in Mediating the Production of Antiangiogenic Proteins in Mouse Muscle2011

    • Author(s)
      Mayu Isotani, Koichi Miyake, Noriko Miyake, Yukihiko Hirai, Takashi Shimada
    • Journal Title

      Cancer Investigation

      Volume: 29 Issue: 5 Pages: 353-359

    • DOI

      10.3109/07357907.2011.584585

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Successful Treatment of Adult MLD Model Mice By Intravenous Injection of Self-Complementary Type 9 AAV Vector Expressing ASA2014

    • Author(s)
      Miyake N, Miyake K, Yamamoto M and Shimada T.
    • Organizer
      17th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Washington DC
    • Related Report
      2013 Final Research Report
  • [Presentation] Minimally invasive gene therapy of MLD model mice by intrathecal and intravenous injection of AAV9 vector2014

    • Author(s)
      Miyake N, Miyake K, and Shimada T.
    • Organizer
      10th WORLDSymposium™
    • Place of Presentation
      San Diego,CA
    • Related Report
      2013 Final Research Report
  • [Presentation] Minimally invasive gene therapy of MLD model mice by intrathecal and intravenous injection of AAV9 vector2014

    • Author(s)
      Miyake N, Miyake K, Shimada T.
    • Organizer
      10th WORLDSymposium™ 2014
    • Place of Presentation
      San Diego, CA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Adeno−Associated Vector (Type 8)−Mediated Expression of siRNA Targeting Vascular Endothelial Growth Factor Efficiently Inhibits Neovascularization in a Murine Choroidal Neovascularization Model2013

    • Author(s)
      Igarashi T, Miyake K, Miyake N, Iijima O, Yaguchi C, Shimada T and Takahashi H.
    • Organizer
      16th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Salt Lake City, Utah
    • Related Report
      2013 Final Research Report
  • [Presentation] Long−Term Secretion of Arylsulfatase A without Antibody Formation after AAV Mediated Neonatal Gene Transfer into MLD Model Mice2013

    • Author(s)
      Miyake N, Miyake K, Yamamoto M and Shimada T.
    • Organizer
      16th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Salt Lake City, Utah
    • Related Report
      2013 Final Research Report
  • [Presentation] Adeno-Associated Vector (Type 8)-Mediated Expression of siRNA Targeting Vascular Endothelial Growth Factor Efficiently Inhibits Neovascularization in a Murine Choroidal Neovascularization Model2013

    • Author(s)
      Igarashi T, Miyake K, Miyake N, Iijima O, Yaguchi C, Shimada T, Takahashi H.
    • Organizer
      16th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Salt Lake City, Utah, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Long-Term Secretion of Arylsulfatase A without Antibody Formation after AAV Mediated Neonatal Gene Transfer into MLD Model Mice2013

    • Author(s)
      Miyake N, Miyake K, Yamamoto M, Shimada T.
    • Organizer
      16th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Salt Lake City, Utah, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Targeted Gene Transfer into the Ependymal Cells and Long-Term Enzyme Replacement in the CSF by Intraventricular Injection of AAV Vector Serotype 12013

    • Author(s)
      Yamazaki Y, Hironaka K, Hirai Y, Miyake K, Shimada T.
    • Organizer
      16th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Salt Lake City, Utah, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] siRNA Targeting Vascular Endothelial Growth Factor by adeno-associated vector (type 8) efficiently inhibits Neovascularization in a Murine Choroidal Neovascularization Model2013

    • Author(s)
      Igarashi T, Miyake N, Iijima O, Yaguchi C, Shimada T, Takahashi H, Miyake K.
    • Organizer
      The 19th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      Okayama,Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Tolerance induction to arylsulfatase A by AAV mediated neonatal gene transfer into MLD model mice2013

    • Author(s)
      Miyake N, Miyake K, Yamamoto M, Shimada T.
    • Organizer
      The 19th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      Okayama, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] AAV9 mediated gene therapy of MLD model mice2012

    • Author(s)
      Miyake N, Miyake K, Sakai A, Yamamoto M, Endo A, Suzuki H, and Shimada T.
    • Organizer
      20th Annual Meeting of the European Society of Gene & Cell Therapy
    • Place of Presentation
      Versailles, France
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Gene therapy of adult MLD model mice by intrathecal administration of type 9 AAV vector2012

    • Author(s)
      Miyake N, Miyake K, Sakai A, Yamamoto M, Endo A, Suzuki H, and Shimada T.
    • Organizer
      15th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Philadelphia, Pennsylvania
    • Related Report
      2013 Final Research Report
  • [Presentation] Gene therapy of adult MLD model mice by intrathecal administration of type 9 AAV vector2012

    • Author(s)
      Miyake N, Miyake K, Sakai A, Yamamoto M, Endo A, Suzuki H, Shimada T
    • Organizer
      15th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Philadelphia, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Successful gene therapy in utero for lethal murine hypophosphatasia2012

    • Author(s)
      Sugano H, Miyake K, Watanabe A, Iijima O, Narisawa S, Millán JL, Fukunaga Y, Shimada T
    • Organizer
      6th Alkaline Phosphatasie and Hypophosphatasia International Symposium
    • Place of Presentation
      Huningue, France
    • Related Report
      2012 Research-status Report
  • [Presentation] Ex vivo gene therapy of severe infantile hypophosphatasia model mice using lentiviral transduced bone marrow cells2012

    • Author(s)
      Iijima O, Sugano H, Watanabe A, Miyake K, Shimada T
    • Organizer
      6th Alkaline Phosphatasie and Hypophosphatasia International Symposium
    • Place of Presentation
      Huningue, France
    • Related Report
      2012 Research-status Report
  • [Presentation] Ex vivo gene therapy of severe infantile hypophosphatasia model mice using lentiviral transduced bone marrow cells2012

    • Author(s)
      Iijima O, Sugano H, Watanabe A, Miyake K, Shimada T
    • Organizer
      The 18th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      熊本
    • Related Report
      2012 Research-status Report
  • [Presentation] Successful treatment of adult MLD model mice by intrathecal administration of type 9 AAV vector2012

    • Author(s)
      Miyake N, Miyake K, Sakai A, Yamamoto M, Endo A, Suzuki H, Shimada T
    • Organizer
      The 18th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      熊本
    • Related Report
      2012 Research-status Report
  • [Presentation] DRG神経におけるmiR-7a過剰発現は神経障害性疼痛を特異的に抑制する2012

    • Author(s)
      坂井敦、齋藤文仁、三宅紀子、三宅弘一、島田隆、鈴木秀典
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] 骨髄細胞移植による低フォスファターゼ症のex vivo遺伝子治療2012

    • Author(s)
      飯島修、菅野華子、鹿子田千津、渡邉淳、三宅弘一、島田隆
    • Organizer
      第57回日本人類遺伝学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Gene therapy of adult MLD model mice by intrathecal administration of type 9 AAV vector2012

    • Author(s)
      Miyake N, Miyake K, Sakai A, Yamamoto M, Endo A, Suzuki H, Shimada T
    • Organizer
      第4回国際ライソゾーム病フォーラム・第17回日本ライソゾーム病研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Rescue of lethal hypophosphatasia mice by neonatal ex vivo gene therapy using lentivirally transduced bone marrow cells2012

    • Author(s)
      Iijima O, Miyake K, Sugano H, Tsutomu I, Chizu K, Watanabe A, Shimada T
    • Organizer
      54th American Society of Hematology Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Intrathecal Administration of Type 9 AAV Vector Expressing Arylsulfatase A Is Effective for Reduction of Sulfatide Storage but Not for Correction of Neurological Deficits in Adult Metachromatic Leukodystrophy Model Mice with Overt Neurological Symptoms2011

    • Author(s)
      Miyake N, Miyake K, Sakai A, Yamamoto M, Endo A, Suzuki H, and Shimada T.
    • Organizer
      14th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Seattle, WA
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of cell targeting strategy using HIV vector pseudtyped with HIV envelope2011

    • Author(s)
      Koichi Miyake, Takashi Shimada
    • Organizer
      The 17th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Book] Development of Muscle-Directed Systemic Cancer Gene Therapy. Novel Gene Therapy Approaches2013

    • Author(s)
      Miyake K, Shimada T
    • Publisher
      Edited by Ming Wei and David Good, Published by InTech
    • Related Report
      2013 Final Research Report
  • [Book] Novel Gene Therapy Approaches2013

    • Author(s)
      Miyake K, Shimada T
    • Total Pages
      450
    • Publisher
      InTech
    • Related Report
      2012 Research-status Report
  • [Book] Development and Application of HIV Vectors Pseudotyped with HIV Envelopes. Viral Gene Therapy2011

    • Author(s)
      Miyake K, Shimada T
    • Publisher
      Edited by Ke Xu, Published by InTech
    • Related Report
      2013 Final Research Report
  • [Book] Viral gene therapy2011

    • Author(s)
      Koichi Miyake, Takashi Shimada
    • Total Pages
      16
    • Publisher
      Intec
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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