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Development of a new classification depend on epigenetic information in pediatric acquired bone marrow failure syndrome

Research Project

Project/Area Number 22659193
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionNagoya University

Principal Investigator

KOJIMA Seiji  名古屋大学, 大学院・医学系研究科, 教授 (20313992)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Yoshiyuki  名古屋大学, 大学院・医学系研究科, 準教授 (40432273)
MURAMATSU Hideki  名古屋大学, 医学部附属病院, 助教 (00572570)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywords内科系臨床医学・小児科学 / 再生不良性貧血 / エピジェネティクス / 骨髄異形成症候群 / パイロシークエンス / エピジエネティクス / 骨髄異形性症候群 / パイロシークエンス法
Research Abstract

The differential diagnosis between aplastic anemia(AA) and hypoplastic myelodysplastic syndrome(MDS), especially, refractory cytopenia of childhood(RCC) is still difficult. Six of 9 RCC specimens showed the TP53 gene mutation in TP53 positive stained cells cut by lazer microdissection system, however, there is no TP53 mutation in AA specimens. Furthermore, 2 of 5 RCC specimens showed the highly methylated status in the promotor region of p16 gene, but not in AA specimens. Higher expression of Evi-1, GATA-2 and AML1/RUNX1 were found than those at AA/MDS phase. We also found AML1/RUNX1 and N-RAS mutations occurred in this process.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (62 results)

All 2012 2011 2010 Other

All Journal Article (34 results) (of which Peer Reviewed: 19 results) Presentation (21 results) Book (6 results) Remarks (1 results)

  • [Journal Article] Epstein-Barr virus(EBV)-associated T/NK lymphoproliferative diseases in non-immunocompromised hosts : prospective analysis of 108 cases2012

    • Author(s)
      Kimura H, Takahashi Y(13人中5番目), Kojima S(13人中6番目), et al
    • Journal Title

      Blood

      Volume: 119(3) Pages: 673-86

    • Related Report
      2011 Final Research Report
  • [Journal Article] Epstein-Barr virus (EBV)-associated T/NK lymphoproliferative diseases in non-immunocompromised hosts : prospective analysis of 108 cases2012

    • Author(s)
      Kimura H, et al
    • Journal Title

      Blood

      Volume: 119(3) Pages: 673-686

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acceptable HLA-mismatching in unrelated donor bone marrow transplantation for patients with acquired severe aplastic anemia2011

    • Author(s)
      Yagasaki H, Kojima S(11人中2番目), et al
    • Journal Title

      Blood

      Volume: 118(11) Pages: 3186-3190

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] The Third Consensus Conference on the treatment of aplastic anemia2011

    • Author(s)
      Kojima S(12人中1番目), et al.
    • Journal Title

      Int J Hematol

      Volume: 93(6) Pages: 832-7

    • NAID

      10029535850

    • Related Report
      2011 Final Research Report
  • [Journal Article] Aberrant phosphorylation of STAT5 by granulocyte-macrophage colony-stimulating factor in infant cytomegalovirus infection mimickingjuvenile myelomonocytic leukemia2011

    • Author(s)
      Nishio N, Takahashi Y(11人中2番目), Muramatsu H(11人中9番目), Kojima S(11人中11番目), et al.
    • Journal Title

      Leuk Res

      Volume: 35(9) Pages: 1261-4

    • Related Report
      2011 Final Research Report
  • [Journal Article] Relapse of aplastic anemia in childrenafter immunosuppressive the rapy : areport from the Japan Childhood Aplastic Anemia Study Group2011

    • Author(s)
      Kamio T, Muramatsu H(21人中11番目) Kojima S(21人中20番目), et al.
    • Journal Title

      Haematologica

      Volume: 96(6) Pages: 814-9

    • Related Report
      2011 Final Research Report
  • [Journal Article] Predicting response to immunosuppressive therapy in childhood aplastic anemia2011

    • Author(s)
      Yoshida N, Takahashi Y(12人中4番目), Kojima S(12人中12番目), et al.
    • Journal Title

      Haematologica

      Volume: 96(5) Pages: 771-4

    • Related Report
      2011 Final Research Report
  • [Journal Article] Reduced-intensity conditioning for alternative donor hematopoietic stem cell transplantation in patients with dyskeratosis congenita2011

    • Author(s)
      Nishio N, Takahashi Y(9人中2番目), Muramatsu H(9人中5番目), KojimaS(9人中9番目), et al.
    • Journal Title

      Pediatr Transplant

      Volume: 15(2) Pages: 161-6

    • Related Report
      2011 Final Research Report
  • [Journal Article] Autoimmune lymphoproliferativesyndrome-like disease with somaticKRAS mutation2011

    • Author(s)
      Takagi M, Muramatsu H(15人中7番目), Kojima S(15人中13番目), et al.
    • Journal Title

      Blood

      Volume: 117(10) Pages: 2887-90

    • Related Report
      2011 Final Research Report
  • [Journal Article] Optimization of Therapy for Severe Aplastic Anemia Based on Clinical, Biological and Treatment Response Parameters : Conclusions of an International Working Group on Severe Aplastic Anemia Convened by the Blood and Marrow Transplant Clinical Trials Network2011

    • Author(s)
      Pulsipher MA, Kojima S(17人中8番目), et al.
    • Journal Title

      Biol Blood Marrow Transplant

      Volume: 17(3) Pages: 291-9

    • Related Report
      2011 Final Research Report
  • [Journal Article] The Third Consensus Conference on the treatment of aplastic anemia2011

    • Author(s)
      Kojima S, et al
    • Journal Title

      Int J Hematol

      Volume: 93(6) Pages: 832-837

    • NAID

      10029535850

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant phosphorylation of STAT5 by granulocyte-macrophage colony-stimulating factor in infant cytomegalovir us infection mimicking juvenile myelomonocytic leukemia2011

    • Author(s)
      Nishio N, et al
    • Journal Title

      Leuk Res

      Volume: 35(9) Pages: 1261-1264

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predicting response to immunosuppressive therapy in childhood aplastic anemia2011

    • Author(s)
      Yoshida N, et al
    • Journal Title

      Haematologica

      Volume: 96(5) Pages: 771-774

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced-intensity conditioning for alternative donor hematopoietic stem cell transplantation in patients with dyskeratosis congenita2011

    • Author(s)
      Nishio N, et al
    • Journal Title

      Pediatr Transplant

      Volume: 15(2) Pages: 161-166

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation2011

    • Author(s)
      Takagi M, et al
    • Journal Title

      Blood

      Volume: 117(10) Pages: 2887-2890

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Optimization of Therapy for Severe Aplastic Anemia Based on Clinical, Biological and Treatment Response Parameters : Conclusions of an International Working Group on Severe Aplastic Anemia Convened by the Blood and Marrow Transplant Clinical Trials Network, March 20102011

    • Author(s)
      Pulsipher MA, et al
    • Journal Title

      Biol Blood Marrow Transplant

      Volume: 17(3) Pages: 291-299

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Optimization of Therapy for Severe Aplastic Anemia Based on Clinical, Biological and Treatment Response Parameters : Conclusions of an International Working Group on Severe Aplastic Anemia Convened by the Blood and Marrow Transplant Clinical Trials Network, March 2010.2011

    • Author(s)
      Pulsipher MA, et a1.
    • Journal Title

      Biol Blood Marrow Transplant.

      Volume: 17(3) Pages: 291-299

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced-intensity conditioning for alternative donor hematopoietic stemcell transplantation in patients with dyskeratosis congenita.2011

    • Author(s)
      Nishio N, et al.
    • Journal Title

      Pediatr Transplant.

      Volume: 15(2) Pages: 161-166

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Excellent outcomes of children with CML treated with imatinib mesylate compared to that in pre-imatinib era.2011

    • Author(s)
      Muramatsu H, et al.
    • Journal Title

      Int J Hematol.

      Volume: 93(2) Pages: 186-191

    • NAID

      10029533124

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predicting response to immunosuppressive therapy in childhood aplasticanemia.2011

    • Author(s)
      Yoshida N, et al.
    • Journal Title

      Haematologica.

      Volume: Epub ahead of print

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent progressin dyskeratosis congenita2010

    • Author(s)
      Nishio N, Kojima S.
    • Journal Title

      Int J Hematol

      Volume: 92(3) Pages: 419-24

    • Related Report
      2011 Final Research Report
  • [Journal Article] Down syndrome and GATA1 mutations in transient abnormal myeloproliferative disorder : mutation classes correlate with progression to myeloid leukemia.2010

    • Author(s)
      Kanezaki R, Kojima S(20人中18番目), et al.
    • Journal Title

      Blood

      Volume: 116(22) Pages: 4631-4638

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Journal Article] Comparison of matched-sibling donorBMT and unrelated donor BMT in children and adolescent with acquired severe aplastic anemia2010

    • Author(s)
      Yagasaki H, Takahashi Y(13人中2番目), Muramatsu H(13人中6番目), Kojima S(13人中13番目), et al.
    • Journal Title

      Bone Marrow Transplant

      Volume: 45(10) Pages: 1508-13

    • Related Report
      2011 Final Research Report
  • [Journal Article] Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia2010

    • Author(s)
      Konno Y, Kojima S(20人中10番目), et al.
    • Journal Title

      Haematologica

      Volume: 95(8) Pages: 1293-9

    • Related Report
      2011 Final Research Report
  • [Journal Article] Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stemcell transplantation2010

    • Author(s)
      Villalobos IB, Takahashi Y(11人中2番目), Muramatsu H(11人中4番目), Kojima S(11人中11番目), et al.
    • Journal Title

      Blood

      Volume: 115(15) Pages: 3158-61

    • Related Report
      2011 Final Research Report
  • [Journal Article] Mutations of E3 ubiquitin ligase Cbl family members but not TET2 mutations are pathogenic in juvenile myelomonocytic leukemia2010

    • Author(s)
      Muramatsu H(14人中1番目), Takahashi Y(14人中10番目), KojimaS(14人中13番目), et al.
    • Journal Title

      Blood

      Volume: 115(10) Pages: 1969-75

    • Related Report
      2011 Final Research Report
  • [Journal Article] Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation.2010

    • Author(s)
      Villalobos IB, et al.
    • Journal Title

      Blood

      Volume: 115(15) Pages: 3158-3161

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia.2010

    • Author(s)
      Konno Y, et al.
    • Journal Title

      Haematologica

      Volume: 95(8) Pages: 1293-1299

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spectrum of molecular defects in juvenile myelomonocytic leukaemia includes ASXL1 mutations.2010

    • Author(s)
      Sugimoto Y, et al.
    • Journal Title

      Br J Haematol.

      Volume: 150(1) Pages: 83-87

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic factors for outcomes of pediatric patients with refractory or relapsed acute leukemia undergoing allogeneic progenitor cell transplantation.2010

    • Author(s)
      Watanabe N, et al.
    • Journal Title

      Biol Blood Marrow Transplant.

      Volume: Epub ahead of print

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of matched-sibling donor BMT and unrelated donor BMT in children and adolescent with acquired severe aplastic anemia.2010

    • Author(s)
      Yagasaki H, et al.
    • Journal Title

      Bone Marrow Transplant.

      Volume: 45(10) Pages: 1508-1513

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent progress in dyskeratosis congenita.2010

    • Author(s)
      Nishio N, Kojima S.
    • Journal Title

      Int J Hematol.

      Volume: 92(3) Pages: 419-424

    • NAID

      10027673231

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation.2010

    • Author(s)
      Takagi M, et al.
    • Journal Title

      Blood

      Volume: Epub ahead of print

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Japan Childhood Aplastic Anemia Study Group. Relapse of aplastic anemia in children after immunosuppressive therapy : a report from the Japan Childhood Aplastic Anemia Study Group

    • Author(s)
      Kamio T, et al
    • Journal Title

      Haematologica

      Volume: 96(6) Pages: 814-819

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Unmanipulated haploidentical hematopoietic stem cell transplantation2012

    • Author(s)
      Kojima S
    • Organizer
      Haploidentical Transplantation-Asia Pacific Meeting Seminar 2010
    • Place of Presentation
      AsanMedical Center(Seoul, Korea)
    • Year and Date
      2012-09-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Allogeneic bone marrow transplantation from HLA mismatched family donors in children with aplastic anemia2011

    • Author(s)
      Muramatsu H.
    • Organizer
      The 53nd ASH Annual Meeting
    • Place of Presentation
      SanDiego, USA
    • Year and Date
      2011-12-12
    • Related Report
      2011 Final Research Report
  • [Presentation] Allogeneic bone marrow transplantation from HLA mismatched family donors in children with aplastic anemia2011

    • Author(s)
      Muramatsu H, et al
    • Organizer
      53th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      サンディエゴコンベンションセンター(San Diego, USA)
    • Year and Date
      2011-12-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] Outcomes in children with severe aplastic nemia receiving bone marrow transplntaion from an HLA-matched family donor or intensive immunosuppressive therapy as first-line treatment2011

    • Author(s)
      Yoshida N, et al
    • Organizer
      53th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      サンディエゴコンベンションセンター(San Diego, USA)
    • Year and Date
      2011-12-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] Comparison of clinical outcome between children with plastic anemia and refractorycytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine2011

    • Author(s)
      Hama A.
    • Organizer
      The 53nd ASH Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2011-12-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Comparison of clinical outcome between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine2011

    • Author(s)
      Hama A, et al
    • Organizer
      53th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      サンディエゴコンベンションセンター(San Diego, USA)
    • Year and Date
      2011-12-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Antithymocyte Globulin (ATG), Cyclosporine (CyA), and Danazol versus ATG and CyA as treatment for children with aplastic anemia : Result of matched-pair analysis2011

    • Author(s)
      Kudo K, et al
    • Organizer
      53th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      サンディエゴコンベンションセンター(San Diego, USA)
    • Year and Date
      2011-12-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Clinical characteristics and treatmento outcome of refractory cytopenia of childhppd (RCC) : A prospective registration through the Japanese Society of Pediatric Hematology2011

    • Author(s)
      Hasegawa D, et al
    • Organizer
      53th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      サンディエゴコンベンションセンター(San Diego, USA)
    • Year and Date
      2011-12-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 小児再生不良性貧血とRefractory cytopenia of childhoodの臨床像の比較:中央診断登録例78例の検討2010

    • Author(s)
      濱麻人, 他
    • Organizer
      第52回日本小児血液学会総会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2010-12-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] 本邦におけるCongenital dyserythropoietic anemia(CDA)の責任遺伝子の解析2010

    • Author(s)
      土居崎小夜子, 他
    • Organizer
      第52回日本小児血液学会総会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2010-12-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Advances in Pediatric Leukemia, Bone Marrow Failure and Hematopoietic Stem Cell Transplantation in Japan : Past, Present and Future2010

    • Author(s)
      Kojima S
    • Organizer
      Texas Children's Cancer Center weekly research seminar series
    • Place of Presentation
      Texas Children's Cancer Center(Houston, USA)
    • Year and Date
      2010-12-09
    • Related Report
      2011 Final Research Report
  • [Presentation] Advances in Pediatric Leukemia, Bone Marrow Failure and Hematopoietic Stem Cell Transplantation in Japan : Past, Present and Future.2010

    • Author(s)
      Kojima S.
    • Organizer
      Texas Children's Cancer Center weekly research seminar series
    • Place of Presentation
      Texas Children's Cancer Center (Houston, USA)
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Gene Alterations In Acute Megakaryoblastic Leukemia (AMKL) : a Comparison of AMKL with and without Down Syndrome.2010

    • Author(s)
      Hama A, et al.
    • Organizer
      52nd ASH annual meeting
    • Place of Presentation
      Orange Country Convention Center (Orland, USA)
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] The telomere length in peripheral blood lymphocytes is a useful predictor of the response to immunosuppressive therapy in patients with acquired aplastic anemia.2010

    • Author(s)
      Takahashi Y, et al.
    • Organizer
      52nd ASH annual meeting
    • Place of Presentation
      Orange Country Convention Center (Orland, USA)
    • Year and Date
      2010-12-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] Increase in NK-cell lysis of leukemic blasts due to loss of mismatched HLA haplotype after haploidentical stem cell transplantation.2010

    • Author(s)
      Takahashi Y, et al.
    • Organizer
      52nd ASH annual meeting
    • Place of Presentation
      Orange Country Convention Center (Orland, USA)
    • Year and Date
      2010-12-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] Low-Dose Cytosine Arabinoside Therapy for Neonates with Down Syndrome (DS) and Transient Leukemia (TL).2010

    • Author(s)
      Muramatsu H, et al.
    • Organizer
      52nd ASH annual meeting
    • Place of Presentation
      Orange Country Convention Center (Orland, USA)
    • Year and Date
      2010-12-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Favorable outcome of children with Juvenile Myelomonocytic Leukemia (JMML) and RAS mutations.2010

    • Author(s)
      土居崎小夜子, 他
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2010-09-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Gene alterations of acute megakaryoblastic leukemia(AMKL) with and without Down syndrome.2010

    • Author(s)
      濱麻人, 他
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Recovery of dificient regulatory T cells after IST or SCT using ATG in children with aplastic anemia.2010

    • Author(s)
      高橋義行, 他
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Unmanipulated haploidentical hematopoietic stem cell transplantation.2010

    • Author(s)
      Kojima S.
    • Organizer
      Haploidentical Transplantation-Asia Pacific Meeting Seminar 2010
    • Place of Presentation
      Asan Medical Center (Seoul, Korea)
    • Year and Date
      2010-07-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Flow-FISH法によるリンパ球テロメア長測定は先天性角化不全症のscreeningに有用である2010

    • Author(s)
      西尾信博, 他
    • Organizer
      第113回日本小児科学会学術集会
    • Place of Presentation
      盛岡市民文化ホール(盛岡)
    • Year and Date
      2010-04-24
    • Related Report
      2010 Annual Research Report
  • [Book] 児特発性再生不良性貧血2011

    • Author(s)
      小島勢二, 他
    • Publisher
      南江堂
    • Related Report
      2011 Final Research Report
  • [Book] 先天性骨髄不全症候2011

    • Author(s)
      小島勢二, 他
    • Publisher
      南江堂
    • Related Report
      2011 Final Research Report
  • [Book] 血液8再生不良性貧血2011

    • Author(s)
      小澤敬也、小島勢二, 他
    • Total Pages
      28
    • Related Report
      2011 Final Research Report
  • [Book] 血液専門医テキスト:小児特発性再生不良性貧血2011

    • Author(s)
      小島勢二, 他
    • Publisher
      南江堂
    • Related Report
      2011 Annual Research Report
  • [Book] 難治性貧血の診療ガイド:先天性骨髄不全症候群2011

    • Author(s)
      小島勢二,他
    • Publisher
      南江堂
    • Related Report
      2011 Annual Research Report
  • [Book] 最新医学別冊新しい診断と治療のABC72血液8再生不良性貧血2011

    • Author(s)
      小澤敬也、小島勢二, 他
    • Total Pages
      228
    • Publisher
      最新医学
    • Related Report
      2011 Annual Research Report
  • [Remarks] 研究結果がまとまり次第掲載予定

    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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