115号 pdf版
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1.2. Fig 1 Amyloid pathology in the brain of an Alzheimer s disease patient A Hippocampal section stained with FSB and DAPI which are markers for amyloid and nucleus respectively Senile plaques arrowhead and neurofibrillary tangles arrow are abundantly present B The same section immunostained with antibodies against Ap red and tau green indicating that senile plaques and neurofibrillary tangles are primarily composed of these amyloidogenic molecules Scale bar 100 um A and B 210000000000000000 HOU 80000 amyloid B peptide Ag 100000000 0000000000000000000000Fig 1
3. PETO SPECTOOOOOOOD 000000000000000000K0000000000 721 057221 o DOJM News No 115 2005
4. OOG 1111 OU 20 5 B 1 1 00 spatial resolution T 0 0 0 00 temporal resolution S N signal noise ratiog O
5. Summary Alzheimer s disease AD is a devastating disorder lead ing to progressive neuronal loss and cognitive deficits and is pathologically characterized by accumulation of brain amy loid including extracellular senile plaques and intracellular neurofibrillary tangles Since formation of amyloid lesions is known to precede clinical onset of the disease by 10 20 years detection of amyloid pathology in brains of living patients could permit prediction of disease onset at a preclinical stage Such a technology also facilitates assessment of emerging therapeutic approaches to AD that are capable of modifying pathological processes Small sized amyloid binding com pounds which have recently been exploited by several in dependent research groups are targeted at visualization of brain amyloid in human subjects by radiological imaging such as positron emission tomography We have also generated a fluorine containing amyloid ligand that is applicable to fluo rine magnetic resonanc
6. JIUIUIUIUIUUDUUUUUHIUUDDUUUUUHUDDUUWD 000000000AB0000000000000000000 61000000000000000
7. 000000200000000000000000000000 o DOJ News No 115 2005 00000000000000000000000 ABE UU 000000000000A80000000000000000 00000000000000000000 00000000
8. 5 APPUDU 102576 000000000 5 20 90 90 000000000000000000Fig 4CmM0000 160 310000000000000Brwker 0 940000000 MRI0000000000 MRIOG000000000000 MRI0000000000000000000 RFOOOOOOG 00000000000MRO000000000000000 000025cm 000000000000000000000 000000000000000 A0 um 0 4 0 2 FSBOOOOOOUOG0O00000000 MRID DU O 4F00000 30247 7 2 0000000000000000000000 T2000000 0000000001 FSB0000000000000 MRID 00000000000000000000000000000 00F 5B000000000 7200000000000000 00000000000000000001 2 5 FSBO O00 000000000000000000000 MROODOOOD 0000000000Fig 4c000000000FSBOOOO C00MO0T1000000000000000000 00 Fig 4H FSBOOO0 BB000000000000000000 Congo red 0000 000000000000000000 BSBU FSBOOODO 000000000000000000000T10000000 Fig 5 MRI detection of amyloid plaques in brains of living APP transgenic m
9. 00000000000000000000 100 0 F0000000000 00000 100 000000000000000000000 MIDD 83 O 11 BBBOOOOOOOODOOOOOODOT trans trans 1 fluoro 2 5 bis 3 hydroxycarbonyl 4 hydroxy styrylbenzene FSB 000000 Fig 2 FSBO BBB000000000000 0200000MFig 4A JBI0000000000000000 00 1959 111 1 1 11 02000000O0FSBOOOT Thioflavin TO0 0000000 000000000000000000000PEIODOOOOU MRI 000000000000000
10. LL ELE EE EE BL BL BE UE UO UI UL D 417 uggagggaggApenuuggaagagagggggggagumuu 00000 00000000000000000000000 Q 71072000000000000000000000000 ABp000000000000000000000000000 GABO000000000000000000000000000 putrescineg 00000000000000 000000000 OO0OOOODABOOOOOOOOOOD 00000000000000000 MROOODODOOOOOO PETO SPECTO00000000000000000000 uguuuuuuuuuuuuuuuuuuuuulluuulil
11. Labeling Kitt II D I U D U Fig 00000000000 alOOOOOOU000000000000000 Fluorescein Labeling Kit AN E H AN p0000000000000000 E E AUD ESFY Gi 40000000 OOOUOUOUOUOOUOUOUOUOUODOOUOUOOOU UUUUUUI 26 o DOJM News No 115 2005 O O L 01111 11111111101111 Fluo 4 AM 2900 Fluo 4 Em Fluo 4 AM special packaging Se Fluo 3 Em TT Fluo 4 Ex Fluo 3 Ex lt gt 00000000000 488nm0 0000000 Fluo 30 0 200 Fluorescence Intensity arb 1 C1 c o 0 Flwo300000000000000 CLSMOO00O0O000 500 M 450 500 550 600 650 Fluo 40 Fluo 300000 C 000000 A000000 ES Fig 1 Fluo 40 0 0 Fluo 300000000101010 9 00000000000000000000000000000 OD00000000000000000000000 Fluo 30 1 umol l Fluo 4 or Fluo 3 20 mmol l HEPES Table 00 0 0 1 mmol l CaCle pH 7 4 1 70 101077 000 SE 10101 ugggugguadugFuo4gggu n Fluo 300 20 S 4000 Fluo 4 Em Fig 2 z 3500 Fluo 3 Em Fluo 40 Ca QO 000 Fluo83QG 00000000 Fluo 3 Ka amp 3000 0 0 4 umol l Fluo 4 K 0 35 umol nn 000000 Fluo 3 aen 00000000000000000O000000000000 2 1500 000000000000000000000000000 5 1000 Fluo 4 AMQ
12. in vvo 00 FSBO00000000000000000000 59 00000000000000 JUIUIUIHIUIUDUDUDUHIUUUUDUODUHUIUUDDUUWD UI DI Hund FSB solution 100 ul 25 000 F308 BSB solution 100 ul 20 000 B525 0000000000000 00 14000000000000000000000 80 80 0 0 120 D 000000000 780040 100 200 0 0 220 0 100000 10 UUDUDDBDIuI BLDIEBEBEHBd Lud uut 4 JUIUUIUUUUUUUOL UU 0 2100 0000000 100000
13. 00000000000000000000ABOOODODODODU 0000000000000AB0000000000000040 000000 20000000000000000000000 0000000A48000000000000000000000 0000000A8000000000000000000000 2004 8 22 0000000000000 1 2 C Wolfson D B Wolfson M Asgharian C E Milan T Ostbye K Rockwood D B Hogan Clinical Progression of Dementia Study Group N Engl J Med 344 1111 2001 3 M Higuchi V M Y Lee J Q Trojanowski nternational Congress Series 1260 The Senescence Accelerated Mouse SAM An Ani mal Model of Senescence eds Nomura Y Takeda T Okuma Y Elsevier Amsterdam the Netherlands pp 69 2004 4 J L Price J C Morris Ann Neurol 45 358 1999 5 23 678 2004 6 W E Klunk M L Debnath J W Pettegrew Neurobiol Aging 15 691 1994 7 S D Styren R L Hamilton G C Styren W E Klunk WE J Histochem Cytochem 48 1223 2000 8 D M Skovronsky B Zhang M P Kung H F Kung J Q Trojanowski V M Y Lee Proc Natl Acad Sci USA 97 7609 2000 9 Z P Zhuang M P Kung C Hou C D M Skovro
14. 000000000 1 1 00000 Thioflavin TO0000000000000000 000005 0000000000000000000000 umuuHuuuuuuuuuutuddgadadulultlululul BF 168j Fig 30000000 0000000000000 PF0000000000000 APPOOOOOOOODOUODOUOOUOODOUODOUDUDODID ex vvo 00000000000000000 00000000 BF 168 5 2 21 2 4 dimethylaminophenyl 6 iodobenzothiazole TZDM 2 4 dimethylaminophenyl 6 iodobenzoxazole IBOX 0000 0000 Fig 300TZDMJ Thioflavin T000000000000 0000000000001BOX0000 1201 n 01111111 01 1 1 01111111111 203070000000 University of California Los Angeles 0 O 2 1 6 2 fluoroethyl methyl amino 2 naphthylethylidene malononitrile FDDNP 000000000000000000 000000
15. OO 15 20 1400 02140040 000000 mg 1 0 00000000000 90 0 4 00 20 0000000 00000000000000000000000000000 000bPD000000000000000000000000 0000000000000 5000000000000000 P7SSCD 0 0 20059
16. 0000000000000000000000000 PETO sPECT0000000000000000000000000 0000000000000000000007 10000000 0000000000000000000000 MCI nn 00000000 1000000000000000000000 0000000000000000000 490000000000 0000000000000 1000000000000000 00000000000 MR 00000000000000 000000000 PETO SPECTO 00000000 1 mmt 0000000000000000000000MRIODOOOD am UU 0000000000000000000000000 MRIO O o DOJ News No 115 2005 MRIOOODOOOOOO 0000 111 1 00000000007T2000000000000000000 000000 T2000000000 000000000000000000007200000000
17. 0 GNDDDDDDDDDDDDDDDDDI 201 S NII sN00000000000000000000000000 08 20 5 4 uuuuHuuuuuuuuuutlaudgdgdguuuuuulub o DOJM News No 115 2005 100000 212 0000000 RI0000000000000000000 00000000000000000 4000000000000 JUIUIUIHIUUDUUDUDUUIUUDUUUODUHUUUUUUDUD SND 00000000000000000000000000 0000009N000000000000000000000
18. JUIUIUIHIUUDIUUUDDUUUUUUUUDUUDUUDUDID 60000000000000000000000 000000 SB100000000000000000000000000 FBOOOOOOOOODOODOODU 000000000000 FSBOOOO 1 000000000000 000000
19. 9000 0000000000000 10 0000000000000 100000000000000000 9000000000 900511 474 LL EMCCDIOOOOOOIO 0 SNO0000000000000001000 200000 200000 1 GD ranee ll I I I Nr UI 9 2 00 image intensifier D D D B B B 887 1 70000000000000000000000000010 0 B 0 MCPg multi channel plate I I 0000000000 00 GaAsP0000000000 60000000 0MCPOOO 08600111 1 0 000 0 0 CCD ugadgaggagaugauggau SNOODOOOODOODOOD O00 CCDg Electron multiplying CCD EMGCDODDDI 7 0 EM gain EMGOO 0 ixong ANDOR IP 00 70000000 uuuuuuuuuuuutt Hu d d d CO
20. OMean Filter OOOO ROIDDDDDDDDDDDDDDDDDDDU Fast Fourier Transform FFT L UU 20 LEE EE EE EE EE B BEL EE BE 7E EE EE ET Median Filte 7 00000000000000000000 2 0000000 503 1 00000000 ONoneighbof 2000000000000000100000 OOO XYOOOOOOOOOOUO Multineighbof 200000000000000020000 XYDDUDUDLD 00000000000000000000 Constrained interactive 300 E point spread 0 function 5 1 1 IU LU DB B mIOBEBIUEULELgLLtlutut S N 1
21. 000 0Congo red0 I B B D H Chrysamine GJ Fig 20 l LiCongored 00000000000000 48000000 0000000000 000 Chrysamine Gr 00000000 0000000000000000 0000000000000 0200000000000000000 Chrysamine G 000 010000 4 Fig 20X340 0 0000 4000 Chrysamine GI D I UI D D uumuuHuuuuuuuuuuuuuuuuuuisluullil 0000000700000 X3400000000000000 uuuuHuHuguuuuuuuuuuuuiuuuuluuulll 00X3401000000000000000000000000 00000000 X340000000000000000000 o DOJM News No 115 2005 0000000090 trans trans 1 bromo 2 5 bis 3 hydroxycarbonyl 4 hydroxy styryloenzene 858 0000 00000000000000000000000Fig 20 BSB guggagggagagngggaagnggpnuguuugAPPnmng 0000000000000 50 0 0000001580 00 IMS Fig 200 0SPECTOOOOO 0000000 1590 03 0000000000000000000 70 C
22. JUIUIUIHUUDUUDUUUIUUDUDUODUHUUUUUUDUD 0000PETODOOOOSPECTOOODOOOOODOOODODO PBOOOAPP0000000000000000 000000 00000PETO0000000000000000000000 000000000000000000000000 0000000000PETOOOODOOOODOOOMCIDODD 1 2 000000000000000MRO0O00000000000 PETO SPECTOOODO 020000000000000000 MIO000000000000000 000000000000 PETO 0000000000000000000000000 sPECTO0000000000000000
23. OUUGLUU UUUUUUUUUUUUUUUUUUUUUUU Fig 2 Imaging oftetramethylrhodamine TMR molecules in different widths EE EE EE EL E EF FL EF E EET EE ETE EE EL EE EE EL EL LI of illumination field Horizontal bars indicate the position of uUgggggguauadaggguugddguggggdudguu illumination and the width is set approximately at 1 a amp c and 10 b amp d um Each bright spot in a amp b indicates a single molecule of TMR Horizontal dotted line in line profiles c d dark level of 0000000000 ddo camera 59 1 thin layered illum
24. UNADDUDUAUUUAUNA DUUUUDDUUDDUOD NA 00000000000000000000000000 00000000000000000000Fig 1M0000 b NADUDUDUD 0000000000000000000 UU NA000000000000000000000000 0000000000000000NA00000000001 C d 000000000000000000 00000000 2111 Fluorescence intensity au distance um
25. 0000000000000AB9000000000000 00000000000000MBOO0O000000000000 MB0000000 20000000000000000000 0000000 ABS0C00000000000000000 000 Co 5 Cl PADAPOO 000 00000000000000000000000000 1 200 Av Re gd e 7 R s 1 000 Absorbance 5 5 5 A O 5 o
26. Quantum Efficiency e e 200 300 400 500 600 700 800 900 1000 Wavelength nm Fig 4 Typical quantum efficiencies of back illuminated Bl front illuminated FI CCD camera and generation Ill Gen III image intensifier Courtecy from Andor technology signal intensity 442 000000 ccD0000000000000000000000000 0 guamtum efficiency QED 000000000000000 0100 0000000X00X0000000 00000000 10 0 1 01 iluminatedg 0 0 back illuminatedg 0000000 OOOOOFig 4M0000000000000000000 00 90 2 NN Ns Average S Noise Floor Nr and Nd Counts 00 0 10 20 30 40 50 60 70 80 90 100 Counts a u Temperature C Fig 5 Signal and noises of CCD camera a illustration of noise sources b properties of video signal S readout n
27. 25 Alkaline Phosphatase Labeling KN 25 Alkaline Phosphatase Labeling Kit SH 25 Biotin Labeling Kit NHe 25 Biotin Labeling Kit SH sesenta ibn gines 25 Fluorescein Labeling 2 25 a 11 0 5 9 26 Fluo 4 AM special packaging 26 o DOJM News No 115 2005 iuuuulullsiuuiuuuluuldiliiiilliliiiiulillil Potential Utility of Amyloid binding Compounds in Diagnosis and Treatment of Alzheimer s Disease uu O Makoto Higuchi 100000 10000000000000 0000000000000000 00000000600000000000000000000 2007000000000000000000 0000000000 0000000752000000000000000000000 00 000000000000000000000000000 20000 0000000000000306000000000
28. 00000000000000000000000000 SBT 000PD0000000 500000000000000000 000000000000SBTOOOOOOODOOOOOOOD 0000DPD00000000000000000000000 10000 00000000 0 2x 10 CFU mll JEE ISS SS mg l SBT DPD 000000000000000000000 000 100000 0000 0 00000000000 0000000 200007 0 0000000000000000000000000 0 DPD000000000000000 020000000000000 1mg1000000 SBTOO 10720 020 581 OO UU 000000000SBIODPDOOOOODODOOOODU 00000000 BI000000000000000000 1 4 o OOOO mg 0 6 000000 2 mg l HOCI O 0 4 lt 2 mg l NH CI DD 0 2 30000000 19 0 000000 200 400 600 800 Time sec lt SBT gt 0000 2 5 ml 3 0 0117 pH5 2 cont 0 25 CyDTA 30 ue lt 20 mmol l SBT 15 we 000000 675nm 500 0 4 000000000 25 mg 50 ul 000000675nm 150 00 lt DPD gt DPD 4 DPD Na5SO 25 mg 0 2mol 000000 pH6 5 cont 0 196 CyDTA 125 OO 2 375 11 10 510 nm 50 009 4 000000000
29. 000000000000FSBOOOMRODOOOOOOOOO 00000000000000000000000 Fig BC 19257600000000 09000000000000000 uguuuiuulliiiitiiliiiutiiliutllitiuttut UDD 00000000MROOOOOOOOODOODUFSBOOOOO 00000 120 25000 Tg2576000 7000000000 000000000 1710000 MRIODT20000 LD MRI000000000000000000000000000 000000000000000000000000000TI0 OOO MIO DUDU MRIOC0000000000000000 00000000000 20000 MRIOOO0 1 00000000000000000Fig 600000 MRI 00000 FSBO0000000000000FSBOOOOO 0100000 240000000000000000000000 000000000000 20mgkg000000000000 000000000000000000000010 80 mg kg 0 000000000000000000Fg 700000000 000 F B000000000000000000000000 o DOJM News No 115 2005 24 months Fig 6 Correlation between MR signal changes and brain amyloid levels A In vivo fluorine MRI performed for normal and APP transgenic mice at different ages intravenously injected with FSB Age dependent increase of amyloid plaques in transgenic mice illustrated by
30. tration Tube00000000000000000000 uuguuluuuuuuuuluuiuuiutliultlul tL Fluorescein Labeling Kit NH2 00000 Labeling Kit UU 1 000 Q6 A6 Q7 AT A8 Q9 A9 o DOJM News No 115 2005 NH Reactive Fluorescein O00 Filtration Tube
31. Fitration tube 00000 3 samples 21 000 LK13 HOOO3800000000000000010000000 50 Biotin Labeling Kit NH2 0 200110 0 UFiltration tube 3 samples 12 000 LK03 000000000000000000000000000000 Biotin Labeling Kit SH 3 samples 12 000 LK10 Fluorescein Labeling Kit NH 6 15 3 samples 21 000 LKO1 0000000000000000000 DPerozidasefAlkaline PhosphataseQ OU 09 lt 0000000 gt 00000000000000000000000000000 100000000000 Florescein0000000000 000000000000000000000000000 10 0000000000 0 000000000000000 Filtration Tube 0000000
32. S NDUUDULULUU 213 efficiencygo o 00000 00000000000000000 sNO000000000000000000000000000 JUIUIUIHIUIUDUUUDUUIUUDUDUODUHUUUUUUDUD 3100000 301 00000000 000000000000000000200000000100 00000000000 fontfocus 000000000000 0000000000000000000000000 0 back focal plane 00000000000000 3 2 1 0 1 2 3 um m NA 1 2 e NA 1 45 Fluorescence intensity a u 10 8 6 4 2 0 2 4 6 8 10 Focus shift um Fig 1 Changes in fluorescence intensity of fluorobead diameter 1 um with shift of focus Objective lenses 60x UPlanApo NA 1 2 WI and NA 1 45 oil Olympus o DOJM News No 115 2005 8 0901 region of interest ROII I II 0200000900 60
33. As500 60 000 Fluoresceinf 0 0 0 0 0 D 0 A280 A500x 0 22 of protein Asoo 500 nmp 000 2 0 280 nm 00 amp epnggumaseonmuinuuddunmnue 60 0000 500 nmt Flvorescein0000000000 00000 Fluorescein 10 B B 0 U D U Fluorescein 280 nm 500 nm 0 0 0 0 g 0 280 500 nm 1 0 0 0 22 00 280 nmp 00 8 B D 000000 Fluorescen 0 000000000000 500nm 00 000 2201 000000000000 1 Fluoresceing 00000 o DOJM News No 115 2005 i 000 110 000 MOLECULAR TECHNOLOGIES INC Dojindo Labeling Kits 000000 Filtration tube 0 0 0 Peroxidase Labeling Kit NH2 0000000000000000N 0000000000 3 samples 17 000 LK11 000000 GH 200000000000 0 NH 0 t Peroxidase Labeling Kit SH N hydroxy succinimide NHS D 0000000000 3 samples 17 000 LK09 0000000000 NH F200000000000000 SHO Alkaline Phosphatase Labeling Kit NH2 0 0 0 maleimide 000000000000000 sHt tt 3 samples 21 000 LK12 Alkaline Phosphatase Labeling Kit SH
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36. 5701001 OO FTCOR PEO000000000000000000 488 FITCO 530 nmp GO 000R PEQ 570 nm 020000000000000000O00FACSOOOOOOD JUIUIUIHIUUDUUDUDUUIUUDUDUOUHIUUUUUUDUD 0000000 50 0000 000000000000000000 1 UUDDUUUUUU Allophycocyanin Labeling Kit NH B Phycoerythrin Labeling Kit NH SH SH R Phycoerythrin Labeling Kit NH SH ul 200 ul 1000 000000000 10 j 0 5 ml 0000 0000000000 37C o DOJM News No 115 2005 000 DoyIiNDO MOLECULAR TECHNOLOGIES INC Allophycocyanin Labeling Kit NH2 B Phycoerythrin Labeling Kit NH2 R Phycoerythrin Labeling Kit NH O NH2 Reactive Phycobiliprotein WS Buffer Filtration Tube P
37. H 2 3 Diaminonaphthalene Fig 2 2 3 Diaminonaphthalene NO 000 Naphthalenetriazole 0000000 20000 Buffer Solution 10 2000 1 10 NaNO Standard Solution 10 1000 0 20 NaNO Standard Solution 10 1000 0 20 Nitrate Reductase 10 10000 21 Enzyme Cofactors 10 1000 D 2f Fluorescence Reagent DAN Solution 1g 200p 0 10 Stop Solution 10 20000 10 NO2 NO3 Assay Kit FX Fluorometric 2 3 Diaminonaphthalene Kit 200 1 25 000 NK08 NO2 NOs Assay Kit C ll Colorimetric Griess Reagent Kit GriessOOOOO0000000000 NOz000000 eulfanilamidet j NO 0 UNaphthylethylenediamine O0 000000000000 UU OHOOOOONOOO000000 2 5 1 46 000000 Gress 0920000000 NO20 NO IU Ll 10 100 umo 1 d a ard B B d d OO 00 0000 0 OO ann NO 2 NOs Assay Kit C II Colorimetric Griess Reagent Kit 1000 344 07991 24 800 NKO5 1 1 11
38. 010 amyloid precursor protein APP 1 1 7 2 APPO 2 OOO uumuuuuuuuuuuuuuuuubbiltilillitLL Li 00000000 0 o DOJM News No 115 2005 daf red HOOG A G COOH HOOC X34 V COOH HOOC 2 5 d COOH HOOC COOH OH COOH COCH i iu CH4CO M S B Fig 2 Congo red derivatives known as candidate tracers for brain amyloid Radiolabeling sites for PET and SPECT are indicated by asterisks uuuuHuuuuuuuuuuluuuddddultltlutlul 0 Congo red Fig 200 Thioflavin S Thioflavin T Fig 30 umuuuuuuuuuuuuuuuu
39. UUIUURNADU UDUDU 000 20059 129 20000 9 30 17 30 000000000000000 0000 FO 000 00 1 E mail komine dojindo co jp TEL 0120 489548 FAX 0120 021557 100 UU UU UU UU UU UU UU UU UU UU UU UU UU UUU U UE UOUE 00000000000000000 RNAUDUDUUD H sRNA07000000000000000000040 H Non coding RNA0000000000000 0000 RNAI D OD UD U D D RNAi LG D D UO U UU AOO OUUU 0 sSRNA000 hwvo000000000 0000000000000000 siRNAQOOOOO 51 D D D 18 NOU 70 20000 o DOJIM News No 115 2005 01 11 1 LL 000000 ABS
40. o DONT News No 115 2005 quud Heview seee 1 000000000000000 4 s 10 Topics on Chemistry 00000000 000000 000000 0000 UOUUUUU 16 Commercial UDDUDD HHH Dee 18 NOU DI D D B sess 21 RU UR DR E 11 RE d RR 26 m RE RE MERE 22 Q amp A Th 8 nf per 24 LL ET D D RR RR D ET RE E ERRORS 9 HERCHEN PET 00 OT eege eegene eege 17 EE EE EE EEE El Te DAN 17 HLH DIE DT UF PANAA 20 O ee AAA Y el I REF 21 SE 9 BSB 5011101 E 9 ABS amaan 18 KUNUIA ene Ln 19 0 01 DD DOOD SBTE EEN 20 0 01 000 SBTO 20 TIE EE 20 BOUR serre 20 NO2 NO3 Assay Kit FX Fluorometric 2 3 Diaminonaphthalene Kit 21 NO 2 NOs Assay Kit C II Colorimetric Griess Reagent ku 21 Peroxidase Labeling Kit NHe 25 Peroxidase Labeling Kit SH
41. Coates Proc SPIE 4626 502 2002 8 _ CG Coates DJ Denvir NG McHale KD Thornbury MA Hollywood J Biomed Opt 9 1244 2004 9 T Tanaami S Otsuki N Tomosada Y Kosugi M Shimizu H Ishida Appl Opt 41 4704 2002 gu Imc 0000 HPQ 0 100000 httpz www nikon instruments jp jon products list model1 aspx 0 20 000000 http www olympus co jp jp lisg bio micro 0 300000000 http www opto line co jp jp index htm 0400000000 http www japanlaser co jp 0 500000000 http www nichia co jp jp product led_top html 0 60 0 http www hpk co jp Jpn products SYS BioJ htm 0 0000000 http Wwww roper co jp Ue 1 nhtbp www andor tech com 0 92000000 http www yokogawa co jp SCANNER 0 100000000000000 http www solution systems com 11000000000000 htp www scbio co jp products guantumdot index html 16 Topics on Chemistry 0000000000000000000000000000 00000000000000000000000000000 00000000000000000000000000000 000000000000000000000000000000 0000000000000000000000000000 0000000000000000000000000000 00 000000000000000000000000000 00000000000000000000000000000 00000000000000000000000000000 000000000MO0O000000000000000000 000000000000000000000000000 0000000000000000000000000000 0000000000000000000 0000 700000 000000000000000000000000
42. II U NHz Reactive Fluorescein DMSO 01 521 0 NHe Reactive Fluorescein HOUOOUOUUOUDUUWUUUUUUUUUUUUUUUO 09 1000 IgG 10 00000 Fluoresceing 40 70 0000000 NH gt Reactive Fluorescein 0000000 tube000000000000000 Fluoresceing 0000000 000000000000 2000000000 10000000000000000 610 fo 22 n A10 Fluorescein D
43. oe i iz 1 set 300 26 200 CODOLOOODIO 1 set 30000 25 600 ugagugugud Cr6 t 1 set 50 20 000 21 16 1 1 set 50000 10 000 HOUTH eoa 1set 50000 27 000 Cr0 1 1 1 set 50000 13 600 o a a RE EU 19561 50000 02000000 Cug 0090 17 800 1 set 50000 8 000 2000000 DO 1 set 30000 15 000 0000000 DODUDDOU ABC 1setjj30 10 800 0000000 DOOOOOODI 1 set 30000 9 600 EE o o ET ELE E lt 1set 30000 19 400 0000000 Foggd 1 set 30000 9 000 DO 0 El EI EI Fe 1 set 500 00 20 600 0000000 Fe UD 1 set 50000 0000000 Ni 1 set 50000 20 000 0000000 NIOOODO 6 000 1 set 50000 7 400 1000000 WH 1561 50000 9 200 01000000 1set 1000000 4 200 1 BI 1 set 100000 8 400 n000 0 H 344 03091 341 03501 343 03321 348 0351 1 345 03761 342 03771 341 03741 348 03751 347 03461 344 03471 340 02231 345 03043 342 03053 347 02241 343 03061 341 03481 348 03491 345 03521 342 03531 341 03121 348 03131 345 03141 0000000 PK04 PK04 50 PKO5 PK05 50 PKO7 PK07 50 PK09 PK09 50 PK10 PK10 50 PK11 PK11 50 PK11 60 PK12 PK12 50 PK13 PK13 50 PK14 PK14 50 PK15 PK15 50 PK15 60 ZU DUU UU UULDLLBLL o DOJM News No 115 2005
44. r AB immunostaining is well correlated with alteration of fluorine MR signals B Scatter plots of changes in fluorine MR open squares and T1 open circles and T2 weighted closed circles proton MR signals versus brain amyloid levels in the hippocampus and entorhinal cortex of APP transgenic mice 00000000 LDer 80mgkg010000000000 000000000MRO0000000000000000 000000000000000000000000000 020 mg kg0000000000000000000000000 JUIUIUIHIUIUDDUUUUUIUDDUUUUUHUUDUUUWD 0000000 1100 110001000000000000000 00000000000900000000000000000 0000024 00000000000000000000000 0000003 000 MRIOCODOODOODOODOUOOOODODU 00000000000000000000000000 MRID 000 lt D RAREO00000000000000000000 000000000000000000000000FSBO TI 0000MRO000000000000000000000040 00000 MRO0000000000000000000000 0000
45. 00 Fig 30 0 000000 PETOOOODOOOU 1 11111 00000 CTU PDDNPODDDODDDDDODDDDDDDDDDDDDUI 4 N methylamino 4 hydroxystilbene SB 19 0 0000000000000000 000000000 PBOOCODOOODODOUOUOOODOOOOOU 000000000000Fig 30 Cog SB 13000000 020000 PETOOOOOOOOOOODOOOOOOOOUDOU PBO000000000000000000000 PIBOO 00000000000000 C 000 AOI987000000000000000000Fig 30 AOI98700000000000000000000000000 0 HOUOOUOUOUOUUUUUUUUUUUUUUUUUUUUUO Du s1000000000000000000 PETO SPECTIDUUDDOD
46. 00000 00000000 1Cug Fg 1000000000000000 00000000000000000000000000000 00000000000000000000000000000 0000000000000Fig 20000000000000 O00000000AFMOCOOOOOOOOOOOOOOOOOO 00000000000000000000000000000 000000000000000000000000000Fig 3 00000000000000000 160 00000000000000000000000000000 000000000000000000000000Fig 400 0000000 thixotropy 0000000 00000000000000000000000000000 00000000000000000000000000000 00000000000000000000000000000 00000000000000000000000000000 0000000000000 00000000000000000000000000000 00000000000000000000000000000 00000000000000000000000000000 Dip Pen Nanolithography t 000000 0000000000000000000000000000 00000000000000000000000000000 0000000000000000000 uuu 1 00000 a P Terech R G Weiss Chem Rev 97 3133 1997 b D J Abdallah R G Weiss Adv Mater 12 1237 2000 c S Shinkai K Murata J Mater Chem 8 485 1998 2 M Shirakawa N Fujita S Shinkai J Am Chem Soc 127 4164 2005 o DOJM News No 115 2005 UU 0000000 UU UUUDUUUUUIUID UI d i 25281 N 6 0 70 7 AS 9 7 a O NH KESE Fig 1 Structure of 1Cu Fig 2 Schematic illustration of self assembly of 1Cu and the subsequent photopolymerization of the assembled 1Cu Fig 3 AFM image of the self assembled 1Cu after UV irradiation FLDS ZIL 1 ZU UB Fig 4 Photographs showi
47. 00000000 49 1 TEL 043 206 3249 FAX 043 253 0396 E mail mhiguchi Onirs go jp OU 100000000000000000000000000000 2 100000000000000000000000000 3 3000000000000000000000000000 K Sato M Higuchi N Iwata T C Saido K Sasamoto Eur J Med M Higuchi N Iwata Y Matsuba K Sato K Sasamoto T C Saido M L Schmidt T Schuck S Sheridan M P Kung H F Kung Z P Zhuang C Bergeron J S Lamarche D Skovronsky B Giasson K Ishikawa K Doh ura Y Kudo N Nishida Murakami Kubo Y T Saito N Iwata S Tsubuki Y Takaki J Takano S M Huang T o DOJM News No 115 2005 LU D 100000000000 10 FSB in DMSO FSB solution 1 Fluoro 2 5 bis 3 carboxy 4 hydroxystyryl benzene 1 DMSO solution E HOOC COOH C24H17FOs 420 39 01000 sDDOUUUUDUDUDUDDUUI 00000000000000000000 BSBH D 200 HOUUUUUOUUUUUUO F MRI0000000000 SB100000000000000000000000000 Congo red 000000000000 BSBOO 200000 000000000000BB00O0000000000000 5 Congo rear 59 D
48. 00000000000 SNOO unev mnmpggnggngugngugdgangaanagdnma 501 00000000000 000000000000000 5 000000000000000000000000Fig SU OO DU accumulation717100000000000000000 59 0 1001 0000000 O00000000 averaging000000000000000 o DOJ News No 115 2005 0 0000000000 0 20 00000000 52 2 9 000000000
49. 0000000000000000 00000000 0000000000000000000Fig 1000 10000 00000000000000000009N0000000 0000000000000000200000000mMO0O0O00 SNOOO 000000000000000000000000 JUIUIUIHIUUDUUUUUUIUDDUUUUUHUUDUUUWD 1 000000 000000 2003 Minsky M U S Patent No 3013467 1961 0000000000000 000 2003 0000000000000000000 0000000 49 000 2004 T Sakurai Y Wakazono Y S Yamamoto S Terakawa Proc SPIE 5322 108 2004 69 invvo 00000000 00000000000000 5 000 2005 7 DJ Denvir CG
50. 000000000000000000000 MIJI 000 MRO00000000000000000000000 00000000000000000 MRIO0000000000 00000000000000 MRO000000000000 3 040100000000000000000000000000 0000007000MROOOOODOODOOODOD 300 50 um 00000000000000MO000000000000 20 mg kg 40 mg kg 80 mg kg Liver Fig 7 Assessment of potential acute toxicity of FSB Wild type mice were intravenously injected with FSB at different doses and multiple organs were sampled 24 hours after the administration No prominent changes are found in any of the tissues from mice treated with 20 and 40 mg kg FSB while tubular necrosis is present in the kidney of mice administered with 80 mg kg FSB arrows Sections are stained with hematoxylin eosin heart liver and kidney and cresyl violet brain 4400000000000000 PEMSPECTOO00 MRI 000000000000000
51. 0000000000000000000000000 09011 engl SHOO 7 CWlase 000000000 TeM0o0000000000000000000000 000 000 0000000000000000000000000 coherence 00000000000000HIDOOOD 000 asana OUUU 00000000000000000HDO0000000000 LED ight emitting diode 0 000000000 000000 LED0000000000000000000000000000 Cool 000 000000000000000000000000 scope0 0 100000000000000 MC DOOOOOOO 4000000 441 CCDOOOOOOIO zz Uz UPHUOOUOUUOUUUUUUUUUUUUUUUUUUUUUO CCD charge coupled devicer ODO LSIOg HOO200000WMO0000000000000000CCD 1289 1 000000000000000 umuuuuuuuuuuuuuuuuiuuuuuluiuuulul 2 2
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53. 0000000F SBOO0OO0O00 Fig 4 Characterization of FSB as a tracer for brain amyloid A A and B Subadjacent sections of temporal cortex from an Alzheimer s disease patient stained with BSB A and FSB B Note that FSB yields a higher contrast of amyloid lesions than does BSB C Fluorescence photomicrogragh of Tg2576 mouse brain after intravenous injection of FSB Intense signals are obtained on amyloid plaques D Vertical bore 9 4 Tesla Bruker microMRI system E MicroMRI probe specifically designed for mouse head F Fluorine MR image of 1 FSB solution in a test tube G n vivo fluorine MR image of mouse brain after injection of 2 5 ul of 2 5 FSB into the bilateral basal ganglia H Corresponding T1 weighted proton MR image Scale bars 100 um A and B 100 um C and 2 mm F H IIS MRI B T2 yalo der HAR E TIWI s Li Ki y o DOJM News No 115 2005 000B5B0100000000000000000000000 00000B5B000000000
54. 00000F BO000000000000000 SHIL 00000480000000000000000000000 000Congored000000000000000000000 1 1 1 Avtio 0000000000000000000 000000 000000000B9 B000000000000000000 g 0000000000000000000000000000 0000000000APP00000000000000000
55. 1 1 1 1 8 1 00 UI HU TPWDWUIDDUOW NO2 NO3 Assay Kit F II Fluorometric 2 3 Diaminonaphthalene Kit 1000 347 07981 NK04 Diethyl ether AV POV 500 ml x 6 346 03931 AVO1 21 22 UL o DOJM News No 115 2005 DOUBLE Lm uguuuiuuuuuuuuuuuuuuull Allophycocyanin APC B Phycoerythrin B PE j 00 R Phycoerythrin R PE L 0 0 00 O Phycobiliproteing 14 2 1 20 1 72 000000000000000000 H000000000 uuuHuHuUHuuuuuiuullgdudddugadgauultlulutlul 000000000 59 S s0000000000000000000000000000 T 000000 100000 0APCO0000000 60 0B PE UR PED 300000000001000000000000 UU Fg 2 OOOOOOO0000 1111 UUIHIDIUUUUUUDUUIUDDUUUUUIUUDUUUUWU APC He Ne 0000 688 nmn Kkr0000000 0 647 nm j 00000 0660 nmm 000000000000 FITCO RPPEQOOO0GArOO00000000000 R PEU Art 0 000 498 nmp 0000000000000 OOU HUUGO OUG
56. 25 mg 50 yi 0 510 nm 150 0 09 000000000 SBT 1 set 100000 7 000 ZK01 50 00000000 sBrq 1000 0 1 300 ZK01 60 500 0 0 5 000 ZK01 60 Lu 100 ml 9 000 ZK01 70 00000 200ml 5 000 ZK01 80 O O L NO L1 D U L o DONT News No 115 2005 NO2 NO Assay Kit FX Fluorometric 2 3 Diaminonaphthalene Kit 10000 30 1 20 000 200000000000 200 NO2 NOs Assay Kit FX0 0 M NO2 NOs Assay Kit F Il 00 0 0 0 NO 0 DAN 2 3 Diaminonaphthalene 00000 000000 NO000000000000000000000 020000000000000 00 NO2 NOs Assay Kit Fll DI ugggmgaggugugaurm 200000000000 000000 NOO00000000000000000000 0200000000000000NOODOOOOOODOOOOU 000000NO00000000000000 NO NOs 0 00000N0 0000N0 0000000000000M ut NOs NO 00000000 NO NOs 10 104moll m 0000000000000000000 NOZNOs Assay Kit Cl 5000 NOz NOs Assay Kit Fl 0000000000000000 b 0000 0000 B NO2 m NO NO NO7 9 NOz NO7 0 5 10 15 NOz or NO NOs u mol l 0 5 10 15 NO2 or NO NOs u mol l Fig 1 NO2 NOs Assay Kit FX 0000000 0 NO g NOz NO3 9000 a Buffer Solution Du 0 0 DMEM O NH
57. 7100 4 D 500 00000000000000000000000000000 500 550 600 650 00000000000000000000000000000 Waen gt 00000000000 Fvo400000000 Ca 0000 00000000 Fig 2 Fluo 4000 Fluo 30 go 0 00 00 000000000000 1 umol i Fluo 4 or Fluo 3 20 mmol l HEPES 0 1 mmol l CaClz pH 7 4 Fluo 4 AMOCOCOOOOOOOOOOOD Table Fluo40 pp Fvo30000000000 Fluo 4 2 0 i 00000041 495nm 508nm A F F Je Fig 3000000000000 10pmol DHPG 2 UDDUDD 0 8 996 0 1 0 0 0 000 Gel 000 9000 fan H ai e EE tt 0000 Canon 60 Fig 3 a Cag 0 00 Fig 3 b Ca 0 0 0 0000000000000 B a y M 70 4 ODO000000000000TTX000000 NE Im JEL sg 0000Ca000000000 9060000 d O Fluo 4 AMD O O 0 Fluo 4 AM 5 umol 45 min Fig 4 a Cal 000 1 Fluo 4 AM 1 mg 39 000 F311 Fig Ab Fluo 4 AM 1 1 0 0 Fluo 4 AM special packaging UUUUDUUDUUUDUDUUUUUUDUDOUUUUUUDU UU 000 50 ug x 8 29 000 F312 0000000000 0120 021557 URL http www dojindo co jp E mail info dojindo co jp 0120 489548 00000000 No 115 1D 170 701000 00000 0000 00000 0000 00000 o 00000000000 DOJINDO LABORATORIES DOJIM News No 115 T
58. Kinzy R Kneuer U Neumann M Rudin M Staufenbiel M Stoeckli K H Wiederhold H U Gremlich Nat Biotechnol 23 577 2005 18 C R Jack Jr M Garwood T M Wengenack B Borowski G L Curran J Lin G Adriany O H J Gr hn R Grimm J F Poduslo Magn Reson Med 52 1263 2004 19 J F Poduslo T M Wengenack G L Curran T Wisniewski E M Sigurdsson S 1 Macura B J Borowski C R Jack CR Jr Neurobiol Dis 11 315 2002 20 Chem 39 573 2004 21 Nat Neurosci 8 527 2005 22 xo V M Y Lee J Q Trojanowski Am J Pathol 159 937 2001 23 H Toyama D Ye M Ichise J S Liow L Cai D Jacobowitz J L Musachio J Hong M Crescenzo D Tipre J Q Lu S Zoghbi D C Vines J Seidel K Katada M V Green V W Pike R M Cohen R B Innis Eur J Nucl Med Mol Imaging 32 593 2005 24 Ando T Sawada T Iwaki J Gen Virol 85 1785 2004 25 Suemoto M Higuchi T C Saido Nat Med 11 434 2005 UD 0000 UU O Makoto Higuchi UB mu 0 0 000 263 8555
59. LO CD CD OU 14 o DOJM News No 115 2005 a EMG x10 EMG x100 EMG x500 b orir gt We m d el EMG x500 1 VO jette nere temata EMG x100 o e amp a d colle eiu EMG x50 Lil b adl iil m uua LAM d d i om TI 1 Weird EMG x10 il Wi i si TW WA ajar id Llu al RT D I Lat yA Wr wg EN ema xs id A Lu A de Lab a MINAMI ema xi i A 8 I3 a 3 Pixels Fig 6 Effect of the electron multiplying gain EMG on S N ratio a frames of fluorobead showing images corresponding to variety of increasing EMG x1 x10 x100 x500 b intensity profiles through the bottom spot are shown for better visualization of S N ratio Courtecy from Andor technology Fig 7 Epi fluorescence images of a bovine endothelial cell labelled with Bodipy Raw image left and x1 000 EMG image right Courtecy from Andor technology E S o o 0 c kl Be 20 M m 55 45 1 1 J 0 20 40 60 80 100 Pixel a u Fig 8 Effect of the image processing on fluorescence images Top raw image middle averaged 10 frames bottom accumulated 10 frames 00000000000000Fig 6870 00000000 00 EM CCDOOOOODOODOO0ONipkow0 0000 OO 0000000 cCswLS 100000000000000000 10000000000 s1000000000 0400000000000000000000000 SND 00000000000000
60. OD LU 60 0000000000000 611 0 uma 000000000000 UU 100000 62 DODO temo DD quantum 00117 t 000000 FFT0000000000000000Z20000000000 00000
61. e imaging fluorine MRI Our method does not require radioactivity from the tracer and thus can circumvent costly production and complex safety control of radioactive materials The tracer for fluorine MRI not only has shown its utility in detection of amyloid plaques that form in brains of mice modeling AD but also offers a potentially prac tical system for pathological screening in living humans More over amyloid binding compounds provide a possibility of radi cal treatment for brain amyloidosis in AD because they could halt amyloid formation by interfering with self association of amyloidogenic molecules PUUIUUUUUDDDUUDU MRIO 000 00000000000000000000Fig 1 M00000 JUIUIUIHIUIUDUUUUUUIUDDUUUUUHUUDDUUWD 00000000000000000000000 00000 200000000000000000 100 000000000 0000000 000000000000000000000
62. hoton excita 0 00 1 22 1 20000000000 1 100000000000000000000000000 10000000000000000000 0MPEOOOIO O00000 total internal 610011 0000000000 o0000000000000000000000000000 0100000000000000Fig 3a40 0 00000000 12 d E 2 n Wavelength nm g S 7 n tf F a 400 ae 520 58D 640 700 Wavelength nm C 100 Exciter Emitter Dichroic Transmission 96 400 i 800 Wa
63. hycobiliprotein Allophycocyanin 0 0 B Phycoerythrin 000 R Phycoerythrin IgG EN 7 HeN 0000 IgG E OO 20000000000 NH2 Reactive Phycobiliprotein 000 IgG WS Butter 100000000000 00000000 gce0000 Reaction Buffer IgG Allophycocyanin Labeling Kit SH B Phycoerythrin Labeling Kit SH R Phycoerythrin Labeling Kit SH 1000 01 2 5111 e Filtration Tube Uit SEU HOCU e 50 200 ug SH Reactive Phycobiliprotein Reducing Agent RA Solution Reaction Buffer WS Buffer D Filtration Tube Phycobiliprotein Allophycocyanin 0 0 B Phycoerythrin R Phycoerythrin 000 C 00 0000 IgG A 200000000000 SH Reactive Phycobiliprotein IgG WS Butter 000000000000 5 OOODOODOOODOT eG 1909 23 24 Q amp A 0111 AAA Fluorescein Labeling Kit NH Q1 A1 Q2 A2 Q3 A3 Q4 A4 Q5 A5 9200000000000000000000000 000 50 0000 0 0 N 000000000000000
64. ice A In vivo fluorine MRI after intravenous injection of FSB 20 mg kg Intense signals are found in the cortex arrows and hippocampus arrowhead B T2 weighted proton MRI obtained after fluorine MR scans Low intensity spots are observed in the cortex arrows while no overt changes are found in the hippocampus C Fluorine MR image superimposed on the corresponding T2 weighted proton MR data D T1 weighted proton MRI performed after fluorine MR scans High intensity areas are found in the cortex arrows and hippocampus arrowhead E and F Ex vivo examination of brain section from the same mouse to detect FSB E and Ap F demonstrating that altered MR signals reflect presence of senile plaques Scale bar 2 mm A F APP transgenic mouse 15 months 20 months A Hormal mouse 20 months Anti AD iF RH MRI x7 Hippocampus ee Entorhinal cortex i E 15 aa E 15 S E E ERD o 2 io x E 3 IT E 5 E e E E 5 B E i an ef B es E oo lt lt D Mi 20 Plaque laad ent Plaque load area FSB 20 mo ko APPO00000000000000000000 MIO OO 00000000000000000000000000Fig sA0D000000000000000000 MRID T2000 00000000000000000 Fig 580000000 10 52 158 MRI 11
65. ination I i 000000000000000000 000000000 312 OOOOFig 2 10000000000 70 1 0 3i3 000000000000 000 OO 0 0 DU confocal microscope7 0 000 500 DO 0 5 D BD stray 90 111 1000000000000000000000 1 0 0 0000000000000000000mutti p
66. luuuuuuiuuulul 0000 PE SPECT 000 Congo red Thioflavin T 000000 uuuuuuuuuuuuuuuuuuuuuullululllilil uuuuuuuuuuuuuuuudgdgdgagauulsluuulil uuuuuuuuuuuusluududdadatulltlululul O Fig 20 30 0000000000000001 Congo red 0 0 0 Fig 2 2 Thioflavin T 0 00 0 0 Fig 3 3 10 1000000000000Fig 3B00 30000000 A B 2 LH 1152 KZ em Thioflavin T WA SOO 8 0 6 Me BTA1 TZDM PIB A IBOX wees b NH BF 168 H NC CH ch n VA Ch FDDNP SB 13 ib x e N o N ELLE AOI987 Fig 3 Non Congo red derivatives known as candidate tracers for brain amyloid A Thioflavin T derivatives B Other derivatives Radiolabeling sites for PET and SPECT are indicated by asterisks 20 10 Congo red I Congored I 000000000000000000008B uggudagagggagagagadggdugauu 7000000
67. ng the thixotropic behavior of the Decalin gel of 1Cu Shirakawa Michihiro 0000 0000 24 0 000 812 8581 0000000000 6 10 1 Tell 092 642 3590 Fax 092 642 3611 E mail 3000htcm mbox nc kyushu u ac jp LL EL BE BE BE 7E 7E UE CT LT 0000 000 Fujita Norifumi 00320 0 000 812 8581 000000000 6 10 1 Telg 092 642 3590 Fax 092 642 3611 E mail nfjtttcm mbox nc kyushu u ac jp 0090 Shinkai Seiji 0 0 607 0 000 812 8581 000000000 6 10 1 Telg 092 642 3585 Fax 092 632 4357 E mail seijitcm mbox nc kyushu u ac jp uuu uut 100000000000000000000000000 00 o DOJM News No 115 2005 JUUU DUUUDUUUUDUUUUUUDUL 0000000000000000000000000000 00000000000000000 00000000O000 00000000000000000000000000000 U B Topics on ChemistryQ 0000000000000 00000000000000000000000000000 0000000000000000000000000000 0
68. nsky T L Gur K Pl sl J Q Trojanowski V M Y Lee H F Kung J Med Chem 44 1905 2001 10 W E Klunk Y Wang G F Huang M L Debnath D P Holt C A Mathis Life Sci 69 1471 2001 11 C A Mathis B J Bacskai S T Kajdasz M E McLellan M P Frosch B T Hyman D P Holt Y Wang G F Huang M L Debnathd W E Klunk Bioorg Med Chem Lett 12 295 2002 12 W E Klunk H Engler A Nordberg Y Wang G Blomavist D P Holt M Bergstr Savitcheva G F Huang S Estrada B Ausen M L Debnath J Barletta J C Price J Sandell B J Lopresti A Wall P Koivisto G Antoni C A Mathis B Langstr Ann Neurol 55 306 2004 13 N Okamura T Suemoto H Shimadzu M Suzuki T Shiomitsu H Akatsu T Yamamoto M Staufenbiel K Yanai H Arai H Sasaki Y Kudo T Sawada J Neurosci 24 2535 2004 14 Z P Zhuang M P Kung C Hou K Pl ssl D Skovronsky T L Gur J Q Trojanowski V M Y Lee H F Kung Nuc Med Biol 28 887 2001 15 K Shoghi Jadid G W Small E D Agdeppa V Kepe L M Ercoli P Siddarth S Read N Satyamurthy A Petric S C Huang J R Barrio Am J Geriatr Psychiatry 10 24 2002 16 N P L G Verhoeff A A Wilson S Takeshita L Trop D Hussey K Singh H F Kung M P Kung S Houle Am J Geriatr Psychia try 12 584 2004 17 M Hintersteiner A Enz P Frey A L Jaton W
69. o o o o Wavelength 560 nm Cell 10 mm 0 200 0 000 0 00 0 10 0 20 0 30 SDS ppm 70 1 SDS T Sodium dodecyl sulfate D E E 507 000000 ml x 20 55 2 000 10 3 0000000 10 4 000 21 50000 10 6 10 7000 90 1 00000 0100000000 ml x 2 55 2 000 ABS I D D D 1000000 22M00000000000000000 2 0000001000000000000000000 33000000000000000000002MOM0000 301000000000 450100000000000000000000000000 010000 pepemi Lr Lt 1 1 50 ml 0000010 v Fig 2 850 1 00000000000000000000000000040 00000000000000 3ppm00000000000 2 000 PHO 30 90000000000 nunt 3 1000000000000000000000000000 000 4 1000000000000000000000000000 O nooo ooo 1000001 0000000 ABS 1set 50000 11 000 347 04181 01000000 ABSOOOO 19561 500 00 PKO1 6 200 344 04191 PK01 50 DUU o DOJM News No 115 2005 111 111 111111 D 01000 OOOOOOUOOOOUOOOUOUOUOOOOOU 00000 JIS000000000 00000000000 0
70. oise Nr and dark current Nd o DOJM News No 115 2005 00000000 SNOOOODOOODOOODOO OO000000 CCDOO 443 0000000 CCDOOOOOODOODOUODOOOOOOOODT reading noise NI 0 0 00 dark current 1 0 I I I UU shot noise N00000Fg 50700000 20000000 Nap 4 m 2 60 111111111111111 111111 0000000 dynamic range D rangel L1 DU 970 6 2 0 1 1 1 049705 10000000000 10000000000000000 0Obinning0 00000000000 XNOOOOOOODO CCDO
71. ongo red III Ii i i Uu DU DU iu Ii i uu Ii i rhioflavin T 0 2 20 Thioflavin T Thioflavin TOOOOOD40000000000000000 uuuuuuuuuuuuuuuuuuuuuulluluulllil uguuuuuuuuuuuuuuuuuuuuulluluull 6 methyl benzothiazole aniline 6 Me BTA G 00 0000 0000000000 Fig 3001 6 Me BTAYQ 00000000 0 000000000000000000BIA 10000000 APPOOOG uuuuuuuuuuuuuuuuuuuuddullullul e hydroxy BTA 10000000000000000000000 Co od dC Pittsburgh Compound B PIBO Fg 3371000000000000 2261
72. velength nm Fig 3 Spectra of fluorescence filters a exciters and emitters for FITC Blue red a hard coating HC and black a semi hard coating SC b dichroic beamsplitters for FITC Green HC Black SC c multiband filter sets for DAPI FITC and Texas Red Blue 3 band exciter Red 3 band emitter Green 3 band dichroic Courtecy from Semrock Fig so0 0000000000000000 DAPIU FITCO TexasRed 0000000000000000000O000 Fig 7 0 0 0 OO000000000000000 anti reflection ARDO D 210000m6M000000000000U00000000U0 hard coating HC 30 010000000000000000Fig 300000000 o DOJM News No 115 2005 911 0000000 314 sNO0
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