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Disruption of vascular integrity by deficiency of PI3K class II αisoform in mice

Research Project

Project/Area Number 23659170
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionKanazawa University

Principal Investigator

TAKUWA Yoh  金沢大学, 医学系, 教授 (60171592)

Co-Investigator(Renkei-kenkyūsha) YOSHIOKA Kazuaki  金沢大学, 医学系, 助教 (80333368)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords分子病態学 / PI 3-キナーゼ / 小胞輸送 / 血管恒常性 / 血管障壁機能 / 血管透過性 / 動脈瘤 / アナフィラキシー / イノシトールリン脂質 / PI3キナーゼ / 血管障害 / イノシトールリン酸
Research Abstract

Class II α isoform of phosphatidylinositol 3-kinase (PI3K-C2α) plays the essential role for vesicular trafficking in vascular endothelial cells. In PI3K-C2α-deleted mice, vascular permeability increase after administration of edematogenic mediator was exaggerated compared with wild-type mice. PI3K-C2α-deleted mice also showed a higher frequency of the formation of dissecting aortic aneurysms. Thus, PI3K-C2α is crucial for maintaining vascular integrity through the distinct action from that of class I PI3K, and suggested to be a potential useful therapeutic target for vascular diseases.

Report

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

    (55 results)

All 2013 2012 2011 Other

All Journal Article (20 results) (of which Peer Reviewed: 19 results) Presentation (30 results) (of which Invited: 4 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Essential role of class II PI3K-C2α in sphingosine-1-phosphate receptor-1 mediated signaling and migration in endothelial cells2013

    • Author(s)
      Biswas K, Yoshioka K, Asanuma K, Okamoto Y, Takuwa N, Sasaki T, TakuwaY
    • Journal Title

      J. Biol. Chem

      Volume: 288 Issue: 4 Pages: 2325-2339

    • DOI

      10.1074/jbc.m112.409656

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sphingosine-1-phosphate as a mediator involved in development of fibrotic diseases2013

    • Author(s)
      Takuwa Y
    • Journal Title

      Biochim Biophys Acta

      Volume: 183 Issue: 1 Pages: 185-192

    • DOI

      10.1016/j.bbalip.2012.06.008

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphingosine-1-Phosphate Signaling and Cardiac Fibrosis.2013

    • Author(s)
      Takuwa N
    • Journal Title

      Inflammation and Regeneration

      Volume: 33 Pages: 96-108

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PI3キナーゼ・ファミリーの血管における生理機能:クラスIIα型PI3キナーゼC2αによる新たな血管恒常性維持機構2013

    • Author(s)
      吉岡 和晃
    • Journal Title

      血管

      Volume: 36 Pages: 1-9

    • NAID

      10031177130

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血管新生の基礎と臨床2013

    • Author(s)
      多久和 陽
    • Journal Title

      Bio Clinica

      Volume: 28 Pages: 16-17

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of endothelial class II PI3K-C2α in angiogenesis and vascular barrier function2012

    • Author(s)
      Yoshioka K, Yoshida K, Cui H, Wakayama T, Takuwa N, Okamoto Y, Du W, Qi X, Asanuma K, Sugihara K, Aki S, Miyazawa H, Biswas K, Nagakura C, Ueno M, Iseki S, Schwartz J.R, Okamoto H, Sasaki T, Matsui O, Asano M, Adams H.R, Takakura N, Takuwa Y
    • Journal Title

      Nature med

      Volume: 18(10) Pages: 1560-1569

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sphingosine-1-phosphate signaling in physiology and diseases2012

    • Author(s)
      Takuwa Y
    • Journal Title

      BioFactors

      Volume: 38 Issue: 5 Pages: 329-337

    • DOI

      10.1002/biof.1030

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Antagonism of sphingosine 1-phosphate receptor 2 causes a selective reduction of portal vein pressure in bile duct-ligated rats2012

    • Author(s)
      Kegeyama Y
    • Journal Title

      Hepatology

      Volume: 56 Issue: 4 Pages: 1427-1438

    • DOI

      10.1002/hep.25780

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of sphingosine kinase 1 prevents ceramide accumulation and ameliorates muscle insulin resistance in high fat-fed mice.2012

    • Author(s)
      Bruce CR, Risis S, Babb JR, Yang C, Kowalski GM, Selathurai A, Lee-Young RS, Weir JM, Yoshioka K, Takuwa Y, Meikle PJ, Pitson SM and Febbraio MA
    • Journal Title

      Diabetes

      Volume: 61 Issue: 12 Pages: 3148-3155

    • DOI

      10.2337/db12-0029

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of endothelial class II PI3K-C2αin angiogenesis and vascular barrier function2012

    • Author(s)
      Yoshioka K, Yoshida K, Cui H, Wakayama T, Takuwa N, Okamoto Y, Du W, Qi X, Asanuma K, Sugihara K, Aki S, Miyazawa H, Biswas K, Nagakura C, Ueno M, Iseki S, Schwartz JR, Okamoto H, Sasaki T,Matsui O, Asano M, Adams HR, Takakura N, Takuwa Y.
    • Journal Title

      Nature med

      Volume: 18 Issue: 10 Pages: 1560-1569

    • DOI

      10.1038/nm.2928

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] G Protein-coupledsphingosine-1-phosphate receptors: potential molecular targets for angiogenic and anti-angiogenic therapies2011

    • Author(s)
      Takuwa N, Okamoto Y, Yoshioka K, Takuwa Y
    • Journal Title

      Biomed Rev

      Volume: 22 Pages: 15-29

    • URL

      http://www.eurochicago.com/wp-content/uploads/2012/03/BMR-22-2011.pdf#page=22

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-suppressive Sphingosine-1-phosphate Receptor-2 Counteracting Tumor-promoting Sphingosine-1-phosphate Receptor-1 and Sphingosine Kinase 1-Jekyll Hidden behind Hyde2011

    • Author(s)
      Takuwa N, Du W, Kaneko E, Okamoto Y, Yoshioka K Takuwa Y
    • Journal Title

      Am J Cancer Res.

      Volume: 1(4) Pages: 460-481

    • URL

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186046/?tool=pubmed

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intraradial administration of fasudil inhibits augmented Rho kinase activity to effectively dilate spastic radial artery in coronary artery bypass grafting surgery2011

    • Author(s)
      Takagi T, Okamoto Y, Tomita S, Sato A, Yamaguchi S, Takuwa Y, Wa tanabe G
    • Journal Title

      J Thorac Cardiovasc Surg

      Volume: 142(2)

    • URL

      http://dx.doi.org/10.1016/j.jtcvs.2011.01.055

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of gomisin A on vascular contraction in rat aortic rings Naunyn-Schmiedeberg2011

    • Author(s)
      Seok YM, Choi YW, Kim GD, Kim HY, Takuwa Y, Kim IK.
    • Journal Title

      Archives of Pharmacology

      Volume: 383(1) Issue: 1 Pages: 45-56

    • DOI

      10.1007/s00210-010-0571-0

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of membrane type1-matrix metalloproteinase(MT1-MMP) in rage activation signalingpathways2011

    • Author(s)
      Kamioka M, Ishibashi T, Ohkawara H, Eguchi R, Sugimoto K, Uekita H, Matsui T, Yamagishi SI, Ando K, Sakamoto T, Sakamoto N, Takuwa Y, Wada I, Shiomi M, Maruyama Y, Takeishi Y.
    • Journal Title

      J Cell Physiol

      Volume: 226(6) Issue: 6 Pages: 1554-1563

    • DOI

      10.1002/jcp.22492

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intraradial administration of fasudil inhibits augmented Rho kinase activity to effectively dilate spastic radial artery in coronary artery bypass grafting surgery2011

    • Author(s)
      Takagi T
    • Journal Title

      J Thorac Cardiovasc Surg

      Volume: 142 Issue: 2 Pages: e59-e65

    • DOI

      10.1016/j.jtcvs.2011.01.055

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumor-suppressive Sphingosine-1-phosphate Receptor-2 Counteracting Tumor-promoting Sphingosine-1-phosphate Receptor-1 and Sphingosine Kinase 1-Jekyll Hidden behind Hyde2011

    • Author(s)
      Takuwa N
    • Journal Title

      Am J Cancer Res

      Volume: 1 Pages: 460-481

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Crucial role of membrane type 1 matrix metalloproteinase (MT1- MMP) in RhoA/Rac1-dependent signaling pathways in thrombin- stimulated endothelial cells.2011

    • Author(s)
      Ando K
    • Journal Title

      J Atheroscler Thromb.

      Volume: 18 Pages: 762-773

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] G Protein-coupled sphingosine-1-phosphate receptors: potential molecular targets for angiogenic and anti-angiogenic therapies.2011

    • Author(s)
      Takuwa N
    • Journal Title

      Biomed Rev

      Volume: 22 Pages: 15-29

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] スフィンゴシン-1-リン酸と炎症2011

    • Author(s)
      多久和 陽
    • Journal Title

      感染・炎症・免疫

      Volume: 41 Pages: 14-25

    • Related Report
      2011 Research-status Report
  • [Presentation] クラスII型PI3キナーゼC2αはメンブレン・トラフィッキング調節を介する血管形成及び恒常性維持に必須である2013

    • Author(s)
      吉岡和晃、多久和典子、岡本安雄、多久和陽
    • Organizer
      第90回日本生理学会
    • Place of Presentation
      タワーホール船堀(東京都)(招待講演)
    • Related Report
      2012 Final Research Report
  • [Presentation] Endothelial PI3K-C2a2013

    • Author(s)
      Yoh Takuwa
    • Organizer
      a class II PI3K in angiogenesis and vascular barrier function Gordon Reseach Conference Vascular Cell Biology
    • Place of Presentation
      Four Points Sheraton / Holiday Inn Express Express Ventura, (U.S.A)
    • Related Report
      2012 Final Research Report
  • [Presentation] Endothelial PI3K-C2a2013

    • Author(s)
      Yoshioka K, Yoshida K, Biswas K, Takuwa Y, et al
    • Organizer
      a class II PI3K, has an essential role in angiogenesis and vascular barrier function. Gordon Reseach Conference Vascular Cell Biology
    • Place of Presentation
      Four Points Sheraton / Holiday Inn Express Express Ventura, (U.S.A)
    • Related Report
      2012 Final Research Report
  • [Presentation] ClassII PI3-kinase2013

    • Author(s)
      Kuntal Biswas, Kazuaki Yoshioka, Yasuo Okamoto, Noriko Takuwa and Yoh Takuwa
    • Organizer
      PI3K-C2alpha, mediates S1P-induced endothelial cell migration through endosomal Rac1 activation Gordon Reseach Conference Vascular Cell Biology
    • Place of Presentation
      Four Points Sheraton / Holiday Inn Express Express Ventura, (U.S.A)
    • Related Report
      2012 Final Research Report
  • [Presentation] ClassII PI3-kinase, PI3K-C2alpha, mediates S1P-induced endothelial cell migration through endosomal Rac1 activation2013

    • Author(s)
      Kuntal Biswas
    • Organizer
      Gordon Reseach Conference Vascular Cell Biology
    • Place of Presentation
      Four Points Sheraton / Holiday Inn Express(USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function.2013

    • Author(s)
      Yoshioka K
    • Organizer
      Gordon Reseach Conference Vascular Cell Biology
    • Place of Presentation
      our Points Sheraton / Holiday Inn Express(USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Endothelial PI3K-C2α, a class II PI3K in angiogenesis and vascular barrier function2013

    • Author(s)
      Yoh Takuwa
    • Organizer
      Gordon Reseach Conference Vascular Cell Biology
    • Place of Presentation
      Four Points Sheraton / Holiday Inn Express(USA)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] スフィンゴシン1-リン酸特異的2 型受容体は内皮型一酸化窒素合成酵素を抑制することによりアナフィラキシーショックに対して保護的に働く2013

    • Author(s)
      崔弘
    • Organizer
      第90回日本生理学会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Related Report
      2012 Annual Research Report
  • [Presentation] クラスII 型PI3 キナーゼC2α はエンドソーム上でのS1P によるRac1 活性化を制御して内皮細胞遊走を調節する2013

    • Author(s)
      Kuntal Biswas
    • Organizer
      第90回日本生理学会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Related Report
      2012 Annual Research Report
  • [Presentation] クラスII型PI3キナーゼC2αはメンブレン・トラフィッキング調節を介する血管形成及び恒常性維持に必須である2013

    • Author(s)
      吉岡和晃
    • Organizer
      第90回日本生理学会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ラスII 型PI3キナーゼC2αはエンドソーム上でのRac1活性化を制御してスフィンゴシン-1-リン酸(S1P)による血管内皮細胞遊走・管腔形成を調節する2012

    • Author(s)
      Kuntal Biswas, 吉岡 和晃, 岡本 安雄, 多久和 典子, 多久和 陽
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県)
    • Related Report
      2012 Final Research Report
  • [Presentation] クラスII型PI3キナーゼC2αは血管形成・血管恒常性維持に必須である2012

    • Author(s)
      吉岡 和晃, 多久和 典子, 岡本 安雄, 多久和 陽
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県)(招待講演)
    • Related Report
      2012 Final Research Report
  • [Presentation] クラスIIα型PI3キナーゼC2αは血管形成に必須である2012

    • Author(s)
      吉岡 和晃、岡本 安雄、多久和 典子、多久和 陽
    • Organizer
      第54回日本脂質生化学会
    • Place of Presentation
      九州大学医学部百年講堂(福岡県)
    • Related Report
      2012 Final Research Report
  • [Presentation] Role of sphingosine-1-phosphate in cardiac remodeling and protection2012

    • Author(s)
      Yoh Takuwa
    • Organizer
      The 1st International Symposium on Lipid Mediators
    • Place of Presentation
      九州大学医学部百年講堂(福岡県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] クラスIIα型PI3キナーゼC2αは血管形成に必須である2012

    • Author(s)
      吉岡 和晃
    • Organizer
      第54回 日本脂質生化学会
    • Place of Presentation
      九州大学医学部百年講堂(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Essential role of class IIα-isoform PI3 kinase (PI3K-C2α) in sphingosine-1-phosphate(S1P-induced endothelial cell migration2012

    • Author(s)
      多久和 陽
    • Organizer
      第7回 スフィンゴテラピィ研究会
    • Place of Presentation
      能登ロイヤルホテル(石川県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Class II PI3K-C2α is essential for vascular barrier integrity2012

    • Author(s)
      Kazuaki Yoshioka
    • Organizer
      International Endotoxin and Innate Immunity Society Meeting 2012
    • Place of Presentation
      学術総合センター(東京都)
    • Related Report
      2012 Annual Research Report
  • [Presentation] クラスII 型PI3 キナーゼC2αは血管新生・恒常性維持に必須である2012

    • Author(s)
      吉岡 和晃
    • Organizer
      第59回中部生理学会
    • Place of Presentation
      自然科学研究機構岡崎コンファレンスセンター(愛知県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Class II PI3 kinase C2α has a crucial role in vascular formation and barrier integrity2012

    • Author(s)
      Kazuaki Yoshioka
    • Organizer
      第20回日本血管生物医学会
    • Place of Presentation
      あわぎんホール(徳島県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] クラスII型PI3キナーゼC2αは血管形成・血管恒常性維持に必須である2012

    • Author(s)
      吉岡 和晃
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] クラスII型PI3キナーゼC2αはエンドソーム上でのRac1活性化を制御してスフィンゴシン-1-リン酸(S1P)による血管内皮細胞遊走・管腔形成を調節する2012

    • Author(s)
      Kuntal Biswas
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] クラスII型PI3キナーゼC2αノックアウトマウスにおける血管障壁機能の異常2012

    • Author(s)
      吉岡和晃
    • Organizer
      第89回日本生理学会大会(招待講演)
    • Place of Presentation
      長野県松本文化会館(長野県)
    • Related Report
      2011 Research-status Report
  • [Presentation] スフィンゴシン-1-リン酸による血管内皮細胞遊走におけるクラスII 型PI3 キナーゼC2α の役割2012

    • Author(s)
      Kuntal Biswas
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      野県松本文化会館(長野県)
    • Related Report
      2011 Research-status Report
  • [Presentation] 血管平滑筋収縮における新しいCa 2+ 標的-ミオシン軽鎖ホスファターゼ2011

    • Author(s)
      多久和 陽
    • Organizer
      第27回スパズム・シンポジウム
    • Place of Presentation
      国立京都国際会館(京都府)招待講演
    • Year and Date
      2011-07-30
    • Related Report
      2012 Final Research Report
  • [Presentation] Endothelial class II PI3K-Ca2a has an essential role for physiological and pathological angiogenesis2011

    • Author(s)
      Kazuaki Yoshioka, Kotaro Yoshida, Hong Cui, Xun Qi, Tomohiko Wakayama, Noriko Takuwa, Yasuo Okamoto, Kazushi Sugihara, Sho Aki, Kuntal Biswas, Masahide Asano, Yo h Takuwa
    • Organizer
      日本分子生物学会第11回春季シンポジウム ポスタ
    • Place of Presentation
      石川県立音楽堂(石川県)
    • Related Report
      2012 Final Research Report
  • [Presentation] Endothelial class II PI3K-Ca2a has an essential role for physiological and pathological angiogenesis.2011

    • Author(s)
      Kazuaki Yoshioka
    • Organizer
      日本分子生物学会第11回春季シンポジウム
    • Place of Presentation
      石川県立音楽堂(石川県)
    • Related Report
      2011 Research-status Report
  • [Presentation] ポリ乳酸―グリコール酸共重合体を基材としたスフィンゴシン-1-リン酸徐放微粒子製剤による持続性放出はマウス虚血肢においてAkt/ERK-eNOSを介して血管新生および血管成熟を促進し血流を回復させる2011

    • Author(s)
      戚 勛
    • Organizer
      日本分子生物学会第11回春季シンポジウム
    • Place of Presentation
      石川県立音楽堂(石川県)
    • Related Report
      2011 Research-status Report
  • [Presentation] Role of Lysophospholipid Mediator Sphingosine-1-phosphate in Cardiac Fibrosis2011

    • Author(s)
      Yoh Takuwa
    • Organizer
      1st Meeting of Asian-Pacific Federation of Inflammation and Regeneration and 第32回日本日本炎症・再生医学会 シンポジウム・招待講演(招待講演)
    • Place of Presentation
      国立京都国際会館(京都府)
    • Related Report
      2011 Research-status Report
  • [Presentation] 血管平滑筋収縮における新しいCa 2+ 標的―ミオシン軽鎖ホスファターゼ2011

    • Author(s)
      多久和 陽
    • Organizer
      第27回スパズム・シンポジウム(招待講演)
    • Place of Presentation
      国立京都国際会館(京都府)
    • Related Report
      2011 Research-status Report
  • [Presentation] Function role of sphingosine-1-phosphate signaling in angiogenesis.2011

    • Author(s)
      Yasuo Okamoto
    • Organizer
      The 1st Asia-Pacific Vascular Biology Meeting and 第19回日本血管生物医学会学術集会(招待講演)
    • Place of Presentation
      東京ステーションコンファレンス(東京都)
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://physiology1.w3.kanazawa-u.ac.jp/

    • Related Report
      2012 Final Research Report
  • [Remarks] 血管分子生理学教室(旧生理学第一講座)

    • URL

      http://physiology1.w3.kanazawa-u.ac.jp/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://physiology1.w3.kanazawa-u.ac.jp/

    • Related Report
      2011 Research-status Report
  • [Patent(Industrial Property Rights)] 血管内皮関門障害に関連した疾患又は症状を予防及び/又は治療するための候補物質のスクリーニング方法2013

    • Inventor(s)
      多久和 陽
    • Industrial Property Rights Holder
      多久和 陽
    • Industrial Property Number
      2013-033893
    • Filing Date
      2013-02-11
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 血管内皮関門障害に関連した疾患又は症状を予 防及び/又は治療するための候補物質のスクリー ニング方法2013

    • Inventor(s)
      多久和 陽
    • Industrial Property Rights Holder
      多久和 陽
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-033893
    • Filing Date
      2013-02-11
    • Related Report
      2012 Annual Research Report

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

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