Oberste establishing enteroviruses in chronic diseases

569 views
497 views

Published on

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
569
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
1
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Oberste establishing enteroviruses in chronic diseases

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±SROPHUDVH FKDLQ UHDFWLRQ 5735
  2. 2. )RU WKH ODUJHVFDOH SURVSHFWLYH VWXGLHV WKDW DUH UHTXLUHG WR ILUPO HVWDEOLVK D FDXVDO UHODWLRQVKLS EHWZHHQ HQWHURYLUXV LQIHFWLRQ DQG GHYHORSPHQW RI SUH GLDEHWLF DXWRLPPXQLW RU SURJUHVVLRQ IURP DXWRLPPXQLW WR FOLQLFDO GLDEHWHV VHQVLWLYH 5735 PHWKRGV PXVW EH XVHG WR GHWHFW YLUXV SULRU WR WKH RQVHW RI GLD EHWLF VPSWRPV :H KDYH GHYHORSHG DQ 57VHPLQHVWHG 35 SURWRFRO WR GHWHFW HQWHURYLUXVHV LQ FOLQLFDO VSHFLPHQV 7KLV PHWKRG LV DSSUR[LPDWHO IROG PRUH VHQVLWLYH WKDQ FRQYHQWLRQDO VLQJOHDPSOLILFDWLRQ 35 )XUWKHU ZH KDYH GHYHORSHG PROHFXODU PHWKRGV WR UDSLGO DQG UHOLDEO LGHQWLI HQWHURYLUXV VHUR WSH ESDVVLQJ WKH FXPEHUVRPH DQG RIWHQ SUREOHPDWLF QHXWUDOL]DWLRQ WHVW 7KH PROHFXODU VHURWSLQJ DSSURDFK ZLOO EH YDOXDEOH LQ H[DPLQLQJ WKH UHODWLRQVKLSV EHWZHHQ SDUWLFXODU YLUXV VHURWSHV RU JHQRWSHV DQG VSHFLILF GLVHDVHV .(:256 HQWHURYLUXV WSH GLDEHWHV PHOOLWXV 5735 VHPLQHVWHG 35 PROHFXODU WSLQJ:KLOH KRVW JHQHWLF GHWHUPLQDQWV KDYH D PDMRU LQIOXHQFH RQ DQ LQGLYLGXDO¶V ULVN RIGHYHORSLQJ WSH GLDEHWHV PHOOLWXV 70
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
  4. 4. GLUHFW FWROWLFLQIHFWLRQ RI EHWD FHOOV UHVXOWLQJ LQ GHVWUXFWLRQ RI EHWD FHOOV DQG ORVV RI FDSDFLW WRVQWKHVL]H LQVXOLQ LL
  5. 5. D YLUXVLQGXFHG LPPXQH UHVSRQVH DJDLQVW LQIHFWHG EHWD FHOOVVXFK DV 7 FHOO±LQGXFHG NLOOLQJ RI YLUXVLQIHFWHG FHOOV LLL
  6. 6. QRQVSHFLILF ³LQQRFHQW $GGUHVV IRU FRUUHVSRQGHQFH 0 6WHYHQ 2EHUVWH HQWHUV IRU LVHDVH RQWURO DQG 3UHYHQWLRQ OLIWRQ 5RDG 1( 0DLOVWRS * $WODQWD *$ 9RLFH ID[ VREHUVWH#FGFJRY $QQ 1 $FDG 6FL ±
  7. 7. ‹ 1HZ RUN $FDGHP RI 6FLHQFHV GRL DQQDOV
  8. 8. $11$/6 1(: 25. $$(0 2) 6,(1(6EVWDQGHU´ NLOOLQJ RI EHWD FHOOV WKURXJK DFWLYDWLRQ RI QRQVSHFLILF LPPXQH PHGLDWRUVDQG LY
  9. 9. LQGXFWLRQ RI DQ DXWRLPPXQH UHVSRQVH WR LVOHW DQWLJHQV E FURVVUHDFWLYLWZLWK YLUDO DQWLJHQV PROHFXODU PLPLFU
  10. 10. RU GLVUXSWLRQ RU QRUPDO LPPXQH WROHUDQFHPHFKDQLVPV 6HYHUDO YLUXVHV KDYH EHHQ SURSRVHG DV LQIHFWLRXV WULJJHUV RI GLDEHWHV EXW WKHHQWHURYLUXVHV IDPLO 3LFRUQDYLULGDH JHQXV (QWHURYLUXV
  11. 11. DUH WKH VXEMHFW RI WKH PRVWLQWHQVH VFUXWLQ DW SUHVHQW 1XPHURXV VWXGLHV KDYH SURYLGHG HYLGHQFH IRU DQDVVRFLDWLRQ EHWZHHQ HQWHURYLUXV LQIHFWLRQ DQG SUHGLDEHWLF DXWRLPPXQLW RU FOLQLFDOGLDEHWHV LDEHWHV LQFLGHQFH KDV EHHQ HSLGHPLRORJLFDOO OLQNHG WR WKH LQFLGHQFH RIHQWHURYLUDO PHQLQJLWLV RU HQWHURYLUXV RXWEUHDNV 6HURORJLF VWXGLHV KDYH VKRZQ WKDWWKHUH LV D FRUUHODWLRQ EHWZHHQ HQWHURYLUXV VHURSUHYDOHQFH LQ SDWLHQWV ZLWK SUHGLDEHWLFDXWRLPPXQLW RU GLDEHWHV FRPSDUHG WR XQDIIHFWHG FRQWURO LQGLYLGXDOV LUHFWHQWHURYLUXV GHWHFWLRQ LQ SDQFUHDV EORRG VHUXP RU VWRRO KDV VXJJHVWHG D WHPSRUDOFRUUHODWLRQ EHWZHHQ HQWHURYLUXV LQIHFWLRQ DQG RQVHW RI GLDEHWHV± (QWHURYLUXVHV DUH DPRQJ WKH PRVW FRPPRQ RI KXPDQ YLUXVHV LQIHFWLQJ DQHVWLPDWHG PLOOLRQ SHRSOH DQQXDOO LQ WKH 8QLWHG 6WDWHV DQG SRVVLEO D ELOOLRQ RUPRUH DQQXDOO ZRUOGZLGH 0RVW LQIHFWLRQV DUH LQDSSDUHQW EXW HQWHURYLUXVHVPD FDXVH D ZLGH VSHFWUXP RI DFXWH GLVHDVH LQFOXGLQJ PLOG XSSHU UHVSLUDWRU LOOQHVVFRPPRQ FROG
  12. 12. IHEULOH UDVK KDQGIRRWDQGPRXWK GLVHDVH DQG KHUSDQJLQD
  13. 13. DVHSWLFPHQLQJLWLV SOHXURGQLD HQFHSKDOLWLV DFXWH IODFFLG SDUDOVLV SDUDOWLF SROLRPHOLWLV
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± GDV 7KH LQWHVWLQDO PXFRVD RU XSSHU UHVSLUDWRU WUDFW LV WKH VLWH RISULPDU LQIHFWLRQ ZLWK VHFRQGDU VSUHDG WR WKH FHQWUDO QHUYRXV VVWHP DQG RWKHUWLVVXHV 9LUHPLD LV XVXDOO VKRUWOLYHG RIWHQ ZDQLQJ EHIRUH WKH RQVHW RI VPSWRPVH[FHSW LQ YHU RXQJ FKLOGUHQ 9LUXV LV H[FUHWHG LQ WKH VWRRO IRU XS WR ZHHNV DYHUDJH± ZHHNV
  15. 15. EXW PD[LPDO YLUXV VKHGGLQJ RFFXUV EHIRUH WKH RQVHW RI VPSWRPV 7KHPD[LPXP YLUXV WLWHU LQ VWRRO LV ∼ LQIHFWLRXV YLUXV SDUWLFOHV SHU JUDP 2I WKH UHFRJQL]HG HQWHURYLUXV VHURWSHV DUH NQRZQ WR LQIHFW KXPDQV ,QDGGLWLRQ WR WKH KXPDQ HQWHURYLUXVHV KXPDQ SDWKRJHQLF YLUXVHV DUH IRXQG LQ RWKHUSLFRUQDYLUXV JHQHUD 5KLQRYLUXV KXPDQ UKLQRYLUXVHV
  16. 16. +HSDWRYLUXV KXPDQ KHSDWLWLV$ YLUXV
  17. 17. 3DUHFKRYLUXV KXPDQ SDUHFKRYLUXVHV DQG IRUPHUO HFKRYLUXVHV DQG UHVSHFWLYHO
  18. 18. DQG .REXYLUXV DLFKLYLUXV DQ DJHQW RI JDVWURHQWHULWLV
  19. 19. 0RVW RI WKHKXPDQ HQWHURYLUXV VHURWSHV ZHUH GLVFRYHUHG DQG GHVFULEHG EHWZHHQ DQG DV D UHVXOW RI WKH DSSOLFDWLRQ RI FHOO FXOWXUH DQG VXFNOLQJ PRXVH LQRFXODWLRQ WR WKHLQYHVWLJDWLRQ RI FDVHV RI LQIDQWLOH SDUDOVLV SDUDOWLF SROLRPHOLWLV
  20. 20. DQG RWKHUFHQWUDO QHUYRXV VVWHP GLVHDVHV 7KH KXPDQ HQWHURYLUXVHV ZHUH RULJLQDOOFODVVLILHG RQ WKH EDVLV RI KXPDQ GLVHDVH SROLRYLUXVHV
  21. 21. UHSOLFDWLRQ DQG SDWKRJHQHVLVLQ QHZERUQ PLFH R[VDFNLH $ DQG % YLUXVHV
  22. 22. DQG JURZWK LQ FHOO FXOWXUH ZLWKRXWFDXVLQJ GLVHDVH LQ PLFH HFKRYLUXVHV
  23. 23. EXW WKH KDYH UHFHQWO EHHQ UHFODVVLILHGEDVHG ODUJHO RQ PROHFXODU SURSHUWLHV LQWR IRXU VSHFLHV $ WKURXJK 6HTXHQFHVLQ YDULRXV SRUWLRQV RI WKH HQWHURYLUXV FRGLQJ UHJLRQ FRUUHODWH ZLWK VSHFLHV EXW RQOFDSVLG VHTXHQFH FRUUHODWHV ZLWK VHURWSH
  24. 24. 2%(567( 3$//$16+ 02/(8/$5 (7(7,21 2) (17(529,586(6 7KH QHXWUDOL]DWLRQ WHVW ORQJ WKH ³JROG VWDQGDUG´ IRU HQWHURYLUXV WSLQJ LV JHQHUDOO UHOLDEOH EXW LW LV ODERULQWHQVLYH DQG WLPHFRQVXPLQJ DQG PD IDLO WR LGHQWLIDQ LVRODWH EHFDXVH RI DJJUHJDWLRQ RI YLUXV SDUWLFOHV RU DQWLJHQLF GULIW WKH ZLGHO XVHGVWDQGDUGL]HG WSLQJ DQWLVHUD ZHUH UDLVHG DJDLQVW SURWRWSH VWUDLQV WKDW ZHUH LVRODWHG WR HDUV DJR
  25. 25. $QWLVHUD WR DOO VHURWSHV DUH QRW JHQHUDOO DYDLODEOH DQG LVRODWHV WKDW DUH QRW RI D NQRZQ KXPDQ HQWHURYLUXV VHURWSH QHZ VHURWSHV RU VHURWSHVWKDW QRUPDOO LQIHFW DQLPDOV RWKHU WKDQ KXPDQV
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′QRQWUDQVODWHG UHJLRQ ),*
  27. 27. RIWHQ FRXSOHG WRSUREHKEULGL]DWLRQ DQG GHWHFWLRQ RI SURGXFW LQ D PLFURSODWH IRUPDW 6SHFLPHQV RIFKRLFH IRU WKH GLUHFW GHWHFWLRQ RI HQWHURYLUXVHV E 5735 DUH VWRRO RU UHFWDO VZDEVWRRO LV SUHIHUUHG EHFDXVH LW FRQWDLQV D ODUJHU DPRXQW RI IHFDO PDWHULDO DQG KHQFHYLUXV
  28. 28. RUR RU QDVRSKDUQJHDO VSHFLPHQV WKURDW VZDE QDVRSKDUQJHDO VZDE RUDVSLUDWH VDOLYD
  29. 29. FHUHEURVSLQDO IOXLG LI WKHUH LV FRQFRPLWDQW 16 GLVHDVH
  30. 30. IUHVKIUR]HQ RU IRUPDOLQIL[HG WLVVXH DQG VHUXPSODVPD 6HUXP DQG SODVPD DUH JHQHUDOO ),*85( 6FKHPDWLF UHSUHVHQWDWLRQ RI WKH HQWHURYLUXV JHQRPH LQGLFDWLQJ UHJLRQVWKDW KDYH EHHQ WDUJHWHG IRU GHYHORSPHQW RI 35 GLDJQRVWLFV 7KH JHQRPH LV D SRVLWLYHVWUDQGHG SRODGHQODWHG 51$ RI ∼ QXFOHRWLGHV ZLWK D YLUDO SURWHLQ %93J
  31. 31. FRYDOHQWO OLQNHG WR WKH ′HQG 7KH JHQRPH LV GLYLGHG LQWR ILYH IXQFWLRQDO UHJLRQV WKH ′QRQWUDQVODWHG UHJLRQ 175
  32. 32. FRQWURO RI YLUDO WUDQVODWLRQ LQLWLDWLRQ DQG LQLWLDWLRQ RI SRVLWLYHVWUDQG 51$ VQWKHVLV
  33. 33. 3 HQFRGHV WKH VWUXFWXUDO SURWHLQV WKDW FRPSULVH WKH YLUXV FDSVLG
  34. 34. 3 DQG 3 HQFRGH WKH QRQVWUXFWXUDO SURWHLQV LQYROYHG LQ 51$ UHSOLFDWLRQ SURWHROWLFSURFHVVLQJ RI SROSURWHLQ DQG KRVW FHOO VKXWGRZQ
  35. 35. DQG ′175 LQYROYHG LQ LQLWLDWLRQ RIQHJDWLYHVWUDQG 51$ VQWKHVLV
  36. 36. $11$/6 1(: 25. $$(0 2) 6,(1(6RQO XVHIXO IRU 5735 LQ LQIDQWV EHFDXVH YLUHPLD PD VWLOO EH SUHVHQW DIWHU RQVHW RIVPSWRPV ,I YLUXV LV GHWHFWHG RQO LQ D QRQVWHULOH VLWH VXFK DV VWRRO RU QDVRSKDUQ[D ODUJH QXPEHU RI SDWLHQWV DUH QHHGHG WR HVWDEOLVK WKH DVVRFLDWLRQ EHWZHHQ LQIHFWLRQDQG GLVHDVH HVSLWH WKH DGYDQWDJHV RI HQWHURYLUXV GHWHFWLRQ E 5735 FKDOOHQJHV UHPDLQ,Q WKH FDVH RI FKURQLF GLVHDVHV WKH YLUXV PD DFW LQGLUHFWO HJ WKURXJK LPPXQHPHGLDWHG SDWKRORJ
  37. 37. 7KH YLUXV PD EH FOHDUHG ZHOO EHIRUH GLVHDVH RQVHW RU YLUXVPD EH SUHVHQW LQ WKH SDWLHQW EXW QRW LQ WKH GLVHDVHG WLVVXH (YHQ LQ DFXWH LOOQHVVHVWKH WLWHU LV UHODWLYHO ORZ LQ DOO VSHFLPHQV $V D UHVXOW D ³FRQYHQWLRQDO´ VLQJOHVWHS5735 DPSOLILFDWLRQ PD QRW EH VHQVLWLYH HQRXJK IRU GLUHFW GHWHFWLRQ IURP WKHRULJLQDO FOLQLFDO VSHFLPHQ HVLJQLQJ D SURVSHFWLYH VWXG DQG FROOHFWLQJ PXOWLSOHVSHFLPHQV DW PXOWLSOH WLPH SRLQWV WKURXJKRXW WKH GXUDWLRQ RI WKH VWXG PD RYHUFRPH VRPH RI WKHVH SUREOHPV KRZHYHU WKH RQO ZD WR VROYH WKH VHQVLWLYLWSUREOHP LV E LQFUHDVLQJ WKH VHQVLWLYLW RI WKH GHWHFWLRQ PHWKRG 7R DGGUHVV WKLVLVVXH ZH KDYH GHYHORSHG DQ HQWHURYLUXVVSHFLILF VHPLQHVWHG 5735 DVVD ′17557VQ35
  38. 38. WKDW WDUJHWV WKH FRQVHUYHG UHJLRQV RI WKH ′175 ),*
  39. 39. ),*85( VKRZV WKH VHQVLWLYLW RI RXU VWDQGDUG FRQYHQWLRQDO 5735 FRPSDUHG ZLWK WKDW RIWKH ′175 57VQ35 7HQIROG VHULDO GLOXWLRQV RI D YLUXV LVRODWH − WR −
  40. 40. ZHUHSUHSDUHG ZLWK XQLQIHFWHG FHOO H[WUDFW DV GLOXHQW 51$ ZDV H[WUDFWHG XVLQJ WKH4,$DPS YLUDO 51$ PLQLNLW 4LDJHQ ,QF 9DOHQFLD $
  41. 41. DQG UHYHUVHWUDQVFULEHGXVLQJ WKH DQWLVHQVH SULPHU 35 ZDV SHUIRUPHG XVLQJ D VLQJOH URXQG RI DPSOLILFDWLRQFRQYHQWLRQDO 35
  42. 42. RU WZR URXQGV RI DPSOLILFDWLRQ VHPLQHVWHG 35
  43. 43. 7KH VHFRQGURXQG RI WKH VHPLQHVWHG DPSOLILFDWLRQ XVHG WKH VDPH SULPHUV DV WKH FRQYHQWLRQDO ),*85( 6HQVLWLYLW RI SDQHQWHURYLUXV 5735 PHWKRGV 0 PROHFXODU ZHLJKWPDUNHU 9LUXV GLOXWLRQV DUH VKRZQ DW WKH WRS RI HDFK SDQHO $
  44. 44. 7LWUDWLRQ RI FRQYHQWLRQDO WZRSULPHU 5735 %
  45. 45. 7LWUDWLRQ RI 57VHPLQHVWHG WKUHHSULPHU
  46. 46. 35
  47. 47. 2%(567( 3$//$16+ 02/(8/$5 (7(7,21 2) (17(529,586(6 35 $PSOLILFDWLRQ SURGXFWV ZHUH YLVXDOL]HG E SRODFUODPLGH JHO HOHFWURSKRUHVLVDQG VWDLQLQJ ZLWK HWKLGLXP EURPLGH 7KH 57VQ35 PHWKRG ),* %
  48. 48. ZDV ∼IROG PRUH VHQVLWLYH WKDQ WKH FRQYHQWLRQDO 5735 ),* $
  49. 49. 7KH −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
  50. 50. XH WR WKH KLJK IUHTXHQF RIUHFRPELQDWLRQ DPRQJ SLFRUQDYLUXVHV±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
  51. 51. )RU ERWK WKH QXFOHRWLGH ),* $
  52. 52. DQGDPLQR DFLG ),* %
  53. 53. SDLUZLVH LGHQWLW GLVWULEXWLRQV WKH VFRUHV IHOO LQWR IRXU FDWHJRULHV 7KH KLJKHVW VFRUHV QXFOHRWLGH LGHQWLW RI ≥ DPLQR DFLG LGHQWLW RI ≥
  54. 54. GHSLFW UHODWLRQVKLSV DPRQJ YLUXVHV RI WKH VDPH VHURWSH 1XFOHRWLGH LGHQWLW VFRUHVIRU SDLUZLVH FRPSDULVRQV ZLWKLQ D VSHFLHV UDQJHG IURP WR DQG GHILQHGD SHDN WKDW ZDV FOHDUO GHOLQHDWHG IURP WKH KRPRORJRXV SDLUV DQG IURP WKH SHDN RIVFRUHV FRPSDULQJ YLUXVHV RI GLIIHUHQW VSHFLHV ),* $
  55. 55. 6FRUHV DPRQJ YLUXVHV LQ+XPDQ (QWHURYLUXV $ +(9$
  56. 56. UDQJHG IURP WR ZKLOH WKRVH DPRQJ+(9 YLUXVHV UDQJHG IURP WR 9LUXVHV LQ +(9% DSSHDUHG WR EHVRPHZKDW PRUH KHWHURJHQHRXV ZLWK VFRUHV UDQJLQJ IURP WR 6FRUHV LQWKH KHWHURORJRXV FRPSDULVRQ SHDN UDQJHG IURP WR QXFOHRWLGH LGHQWLWDQG GHSLFW UHODWLRQVKLSV EHWZHHQ VHURWSHV RI GLIIHUHQW VSHFLHV 7KH ILQDO SHDNFRQWDLQLQJ WKH ORZHVW VFRUHV UHSUHVHQWHG FRPSDULVRQV RI YLUXVHV RI GLIIHUHQW JHQHUDZLWKLQ WKH IDPLO 3LFRUQDYLULGDH ,Q WKH DPLQR DFLG LGHQWLW GLVWULEXWLRQ ),* %
  57. 57. WKH KHWHURORJRXV VSHFLHV SHDN DSSHDUHG WR EH FRPSRVHG RI WZR RYHUODSSLQJ SHDNV7KH SHDN ZLWK KLJKHU VFRUHV UHSUHVHQWHG FRPSDULVRQV RI YLUXVHV IURP SKORJHQHWLFDOO UHODWHG VSHFLHV HJ +(9% DQG +(9
  58. 58. ZKHUHDV WKH SHDN ZLWK ORZHU VFRUHVUHSUHVHQWHG FRPSDULVRQV DPRQJ YLUXVHV RI PRUH GLVWDQWO UHODWHG VSHFLHV HJ+(9$ DQG +(9%
  59. 59. 3UDFWLFDO FULWHULD PXVW EH HVWDEOLVKHG EHIRUH PROHFXODU VHTXHQFH LQIRUPDWLRQ FDQEH DSSOLHG URXWLQHO WR SLFRUQDYLUXV LGHQWLILFDWLRQ $ SDUWLDO RU FRPSOHWH 93 QXFOHRWLGH VHTXHQFH LGHQWLW RI DW OHDVW PLQLPXP DPLQR DFLG VHTXHQFH LGHQWLW
  60. 60. EHWZHHQ D FOLQLFDO HQWHURYLUXV LVRODWH DQG VHURWSH SURWRWSH VWUDLQ PD EH XVHG WRHVWDEOLVK WKH VHURWSH RI WKH LVRODWH 7KHVH FULWHULD DOVR DSSHDU WR DSSO WRFRPSDULVRQV DPRQJ LVRODWHV RI IRRWDQGPRXWKGLVHDVH YLUXV IDPLO 3LFRUQDYLULGDHJHQXV $SKWKRYLUXV
  61. 61. EXW D VWXG GLUHFWO FRPSDUDEOH WR WKH HQWHURYLUXV VWXGLHV KDV
  62. 62. $11$/6 1(: 25. $$(0 2) 6,(1(6 ),*85( )UHTXHQF GLVWULEXWLRQ RI SDLUZLVH LGHQWLW VFRUHV IRU FRPSDULVRQ RI 93QXFOHRWLGH DQG GHGXFHG DPLQR DFLG VHTXHQFHV $
  63. 63. 1XFOHRWLGH VHTXHQFH GLVWULEXWLRQ %
  64. 64. $PLQRDFLG VHTXHQFH GLVWULEXWLRQ
  65. 65. ([DPSOH RI WKH DSSOLFDWLRQ RI SDUWLDO 93 VHTXHQFH FRPSDULVRQVWR WKH LGHQWLILFDWLRQ RI FOLQLFDO LVRODWHVQRW HW EHHQ SHUIRUPHG $ EHVWPDWFK QXFOHRWLGH VHTXHQFH LGHQWLW RI EHWZHHQ DQG RU D VHFRQGKLJKHVW VFRUH RI JUHDWHU WKDQ PD SURYLGH D WHQWDWLYH LGHQWLILFDWLRQ SHQGLQJ FRQILUPDWLRQ E RWKHU PHDQV VXFK DV QHXWUDOL]DWLRQ ZLWK PRQRVSHFLILF DQWLVHUD RU PRUH H[WHQVLYH VHTXHQFLQJ $ EHVWPDWFK QXFOHRWLGH VHTXHQFHLGHQWLW EHORZ OHVV WKDQ DPLQR DFLG VHTXHQFH LGHQWLW
  66. 66. PD LQGLFDWH WKDWWKH LVRODWH UHSUHVHQWV DQ XQNQRZQ VHURWSH 6HTXHQFLQJ RI WKH FRPSOHWH FDSVLGFRGLQJ UHJLRQ PD EH XVHIXO LQ FRQILUPLQJ WKLV UHVXOW EXW FRPSOHWH FDSVLG VHTXHQFHVDUH DYDLODEOH IRU OHVV WKDQ KDOI RI WKH NQRZQ HQWHURYLUXV VHURWSHV OLPLWLQJ WKH XWLOLWRI FRPSOHWH FDSVLG VHTXHQFH FRPSDULVRQV XQWLO PRUH VHTXHQFH EHFRPHV DYDLODEOH0RUH H[WHQVLYH FKDUDFWHUL]DWLRQ SRVVLEO LQFOXGLQJ FRPSOHWH JHQRPH VHTXHQFHV PDEH UHTXLUHG IRU YLUXVHV WKDW DSSHDU WR UHSUHVHQW SUHYLRXVO XQNQRZQ JHQHUD± 5HFRJQL]LQJ WKH WHFKQLFDO GLIILFXOWLHV DQG OLPLWDWLRQV LQKHUHQW LQ WKH FODVVLFDSSURDFK WR HQWHURYLUXV LGHQWLILFDWLRQ ZH GHYHORSHG 5735 DQG VHTXHQFLQJ SULPHUVWKDW WDUJHW WKH 93 FDSVLG JHQH DQG PD EH XVHG WR GHWHUPLQH HQWHURYLUXV VHURWSHE VHTXHQFLQJ RI WKH DPSOLFRQ DQG FRPSDULVRQ WR D GDWDEDVH RI WKH 93 VHTXHQFHVRI DOO HQWHURYLUXV VHURWSHV 2XU ILUVW VHW RI SULPHUV DPSOLILHG WKH SURWRWSHVWUDLQV RI RI WKH HQWHURYLUXV VHURWSHV DV ZHOO DV FOLQLFDO LVRODWHV RI VHYHUDODGGLWLRQDO VHURWSHV 7KHVH SULPHUV
  67. 67. DPSOLI D SURGXFW RI ∼ ESFRUUHVSRQGLQJ WR WKH ′KDOI RI 93 ),*
  68. 68. EXW WKH IDLOHG WR DPSOLI VRPH RI WKHSURWRWSH VWUDLQV SULPDULO EHFDXVH RI YDULDELOLW LQ WKH DQQHDOLQJ VLWH RI SULPHU LQ $ 7KH IDLOXUH RI SULPHUV WR DPSOLI DOO HQWHURYLUXV VHURWSHV
  69. 69. 2%(567( 3$//$16+ 02/(8/$5 (7(7,21 2) (17(529,586(6 OLPLWHG WKHLU XVHIXOQHVV LQ URXWLQH GLDJQRVWLF WHVWLQJ $QDOVLV RI WKH FRPSOHWH93 DPLQR DFLG VHTXHQFHV RI DOO HQWHURYLUXV VHURWSHV UHYHDOHG DPLQR DFLGPRWLIV WKDW ZHUH KLJKO FRQVHUYHG DPRQJ DOO VHURWSHV FRUUHVSRQGLQJ WR 93 DPLQRDFLGV 147
  70. 70. $$9
  71. 71. (7* DQG 0),
  72. 72. 933* UHVSHFWLYHO $ SULPHU VHW WDUJHWLQJ WKHVLWHV HQFRGLQJ WKHVH PRWLIV ZDV GHYHORSHG IRU LGHQWLILFDWLRQ RI LVRODWHV WKDW ZHUH QRWDPSOLILHG E 3ULPHUV DQG DQQHDO WR DQDORJRXV VLWHVHQFRGLQJ WKH 147
  73. 73. $$9
  74. 74. (7* PRWLI LQ YLUXVHV RI +(9% +(9 DQG DQG+(9$ UHVSHFWLYHO ),*
  75. 75. 3ULPHU UHSUHVHQWV D FRQVHQVXV RI DQG ),*
  76. 76. 3ULPHU DQQHDOV WR WKH VLWH HQFRGLQJ WKH 0),
  77. 77. 933* PRWLI 3ULPHUV DQG
  78. 78. DPSOLI DOO HQWHURYLUXV VHURWSHV SURGXFLQJ D 35SURGXFW RI DERXW QXFOHRWLGHV DQG DOORZLQJ WKH VLPSOH DQG UDSLG LGHQWLILFDWLRQ RIDQ HQWHURYLUXV LVRODWH 6RPH KXPDQ UKLQRYLUXVHV PD DOVR EH DPSOLILHG $Q H[DPSOHRI WKH DSSOLFDWLRQ RI WKLV VVWHP LV VKRZQ LQ ),*85( 7KH KLJKHVW VFRUHV IRU RIWKH LVRODWHV $5 $= 0 DQG $
  79. 79. ZHUH JUHDWHUWKDQ UDQJLQJ IURP WR 7KHVH KLJK VFRUHV ZHUH FOHDUO UHVROYHGIURP WKH VHFRQGKLJKHVW VFRUHV ZKLFK ZHUH WR % FRQWUDVW WKH KLJKVFRUH IRU 7; ZDV RQO WR HFKRYLUXV
  80. 80. DQG WKH VHFRQGKLJKHVW VFRUHZDV WR HQWHURYLUXV
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± 6(( 0 -* 7,//(6 7KH SDWKRJHQHVLV RI YLUDOLQGXFHG GLDEHWHV OLQ LDJQ 9LURO ± /(,1,.., 3 9LUXVHV DQG WSH GLDEHWHV HOXVLYH SUREOHPV DQG HOXVLYH DQVZHUV OLQ LDJQ 9LURO ± +g7 + HW DO (QWHURYLUXV LQIHFWLRQV DQG LQVXOLQ GHSHQGHQW GLDEHWHV PHOOLWXV²HYLGHQFH IRU FDXVDOLW OLQ LDJQ 9LURO ± .$5921(1 0 HW DO $ UHYLHZ RI WKH UHFHQW HSLGHPLRORJLFDO GDWD RQ WKH ZRUOGZLGH LQFLGHQFH RI WSH LQVXOLQGHSHQGHQW
  82. 82. GLDEHWHV PHOOLWXV :RUOG +HDOWK 2UJDQLVDWLRQ ,$021 3URMHFW LDEHWRORJLD ± +,/781(1 0 HW DO ,VOHW FHOO DQWLERG VHURFRQYHUVLRQ LQ FKLOGUHQ LV WHPSRUDOO DVVRFLDWHG ZLWK HQWHURYLUXV LQIHFWLRQV - ,QIHFW LV ± +(/)$1 5) HW DO 6HURORJLF HYLGHQFH RI DQ DVVRFLDWLRQ EHWZHHQ HQWHURYLUXVHV DQG WKH RQVHW RI WSH GLDEHWHV PHOOLWXV 3LWWVEXUJK LDEHWHV 5HVHDUFK *URXS - ,QIHFW LV ± 221 -: HW DO ,VRODWLRQ RI D YLUXV IURP WKH SDQFUHDV RI D FKLOG ZLWK GLDEHWLF NHWRDFLGRVLV 1 (QJO - 0HG ±
  83. 83. $11$/6 1(: 25. $$(0 2) 6,(1(6 $15(2/(77, / HW DO HWHFWLRQ RI R[VDFNLH % YLUXV 51$ VHTXHQFHV LQ ZKROH EORRG VDPSOHV IURP DGXOW SDWLHQWV DW WKH RQVHW RI WSH , GLDEHWHV PHOOLWXV - 0HG 9LURO ± /(0(176 *% HW DO R[VDFNLH % YLUXV LQIHFWLRQ DQG RQVHW RI FKLOGKRRG GLDEHWHV /DQFHW ± 025(16 0 0$ 3$//$16+ (SLGHPLRORJ ,Q +XPDQ (QWHURYLUXV ,QIHFWLRQV SS ± $60 3UHVV :DVKLQJWRQ 3$//$16+ 0$ 53 5226 (QWHURYLUXVHV SROLRYLUXVHV FR[VDFNLHYLUXVHV HFKRYLUXVHV DQG QHZHU HQWHURYLUXVHV ,Q )LHOGV¶ 9LURORJ SS ± /LSSLQFRWW :LOOLDPV :LONLQV 3KLODGHOSKLD%DOWLPRUH 0$57,12 7$ HW DO (QWHURYLUDO PRFDUGLWLV DQG FDUGLRPRSDWK D UHYLHZ RI FOLQLFDO DQG H[SHULPHQWDO VWXGLHV ,Q +XPDQ (QWHURYLUXV ,QIHFWLRQV SS ± $60 3UHVV :DVKLQJWRQ .,0 .6 HW DO 7KH JURXS % FR[VDFNLHYLUXVHV DQG PRFDUGLWLV 5HY 0HG 9LURO ± 5(:(56 0 0 $7.,1621 7KH SRVVLEOH UROH RI HQWHURYLUXVHV LQ GLDEHWHV PHOOLWXV ,Q +XPDQ (QWHURYLUXV ,QIHFWLRQV SS ± $60 3UHVV :DVKLQJWRQ $/$.$6 0 (QWHURYLUXVHV DQG KXPDQ QHXURPXVFXODU GLVHDVHV ,Q +XPDQ (QWHURYLUXV ,QIHFWLRQV SS ± $60 3UHVV :DVKLQJWRQ 200,77(( 21 (17(529,586(6 ODVVLILFDWLRQ RI KXPDQ HQWHURYLUXVHV 9LURORJ ± 3$1(/ )25 3,251$9,586(6 3LFRUQDYLUXVHV FODVVLILFDWLRQ RI QLQH QHZ WSHV 6FLHQFH ± .,1* $04 HW DO 3LFRUQDYLULGDH ,Q 9LUXV 7D[RQRP 6HYHQWK 5HSRUW RI WKH ,QWHUQDWLRQDO RPPLWWHH RQ 7D[RQRP RI 9LUXVHV SS ± $FDGHPLF 3UHVV 6DQ LHJR /,0 .$ 0 %(1(6+0(/1,. 7SLQJ RI YLUXVHV E FRPELQDWLRQV RI DQWLVHUXP SRROV DSSOLFDWLRQ WR WSLQJ RI HQWHURYLUXVHV R[VDFNLH DQG (+2
  84. 84. - ,PPXQRO ± 527%$57 +$ -5 520(52 /DERUDWRU GLDJQRVLV RI HQWHURYLUDO LQIHFWLRQV ,Q +XPDQ (QWHURYLUXV ,QIHFWLRQV SS ± $60 3UHVV :DVKLQJWRQ 527%$57 +$ HW DO LDJQRVLV RI HQWHURYLUXV LQIHFWLRQ E SROPHUDVH FKDLQ UHDFWLRQ RI PXOWLSOH VSHFLPHQ WSHV 3HG ,QIHFW LV - ± $1* ) HW DO *HQRWSHVSHFLILF LQ YLWUR DPSOLILFDWLRQ RI VHTXHQFHV RI WKH ZLOG WSH SROLRYLUXVHV IURP 0H[LFR DQG *XDWHPDOD 9LUXV 5HV ± 0,125 3 $QWLJHQLF VWUXFWXUH RI SLFRUQDYLUXVHV XUU 7RS 0LFURELRO ,PPXQRO ± 0$7(8 0* $QWLERG UHFRJQLWLRQ RI SLFRUQDYLUXVHV DQG HVFDSH IURP QHXWUDOL]DWLRQ 9LUXV 5HV ± 2%(567( 06 HW DO 0ROHFXODU HYROXWLRQ RI WKH KXPDQ HQWHURYLUXVHV FRUUHOD WLRQ RI VHURWSH ZLWK 93 VHTXHQFH DQG DSSOLFDWLRQ WR SLFRUQDYLUXV FODVVLILFDWLRQ - 9LURO ± .23(.$ + HW DO *HQRWSLF YDULDWLRQ LQ FR[VDFNLHYLUXV % LVRODWHV IURP WKUHH GLIIHUHQW RXWEUHDNV LQ WKH 8QLWHG 6WDWHV 9LUXV 5HV ± .,1* $04 *HQHWLF UHFRPELQDWLRQ LQ SRVLWLYH VWUDQG 51$ YLUXVHV ,Q 51$ *HQHWLFV SS ± 5 3UHVV %RFD 5DWRQ )/ 6$177, - HW DO (YLGHQFH RI UHFRPELQDWLRQ DPRQJ HQWHURYLUXVHV - 9LURO ± 2%(567( 06 HW DO 7SLQJ RI KXPDQ HQWHURYLUXVHV E SDUWLDO VHTXHQFLQJ RI 93 - OLQ 0LFURELRO ± 2%(567( 06 HW DO RPSDULVRQ RI FODVVLF DQG PROHFXODU DSSURDFKHV IRU WKH LGHQWLILFDWLRQ RI ³XQWSDEOH´ HQWHURYLUXVHV - OLQ 0LFURELRO ± 926/22 : HW DO *HQHWLF UHODWLRQVKLSV EHWZHHQ VRXWKHUQ $IULFDQ 6$7 LVRODWHV RI IRRWDQGPRXWKGLVHDVH YLUXV (SLGHPLRO ,QIHFW ± 2%(567( 06 HW DO 0ROHFXODU LGHQWLILFDWLRQ RI QHZ SLFRUQDYLUXVHV DQG FKDUDFWHUL]DWLRQ RI D SURSRVHG HQWHURYLUXV VHURWSH - *HQ 9LURO ± +3,b 7 HW DO $ GLVWLQFW SLFRUQDYLUXV JURXS LGHQWLILHG E VHTXHQFH DQDOVLV 3URF 1DWO $FDG 6FL 86$ ±
  85. 85. 2%(567( 3$//$16+ 02/(8/$5 (7(7,21 2) (17(529,586(6 0$59,/ 3 HW DO $YLDQ HQFHSKDORPHOLWLV YLUXV LV D SLFRUQDYLUXV DQG LV PRVW FORVHO UHODWHG WR KHSDWLWLV $ YLUXV - *HQ 9LURO ± 1,./$6621 % HW DO $ QHZ SLFRUQDYLUXV LVRODWHG IURP EDQN YROHV OHWKULRQRPV JODUHROXV
  86. 86. 9LURORJ ± $0$6+,7$ 7 HW DO RPSOHWH QXFOHRWLGH VHTXHQFH DQG JHQHWLF RUJDQL]DWLRQ RI $LFKL YLUXV D GLVWLQFW PHPEHU RI WKH 3LFRUQDYLULGDH DVVRFLDWHG ZLWK DFXWH JDVWUR HQWHULWLV LQ KXPDQV - 9LURO ±

×