0ccccbca4fec2f27cf61d0e4d174378a 270594.pdf 6a3a26e9998cf47832ca843ed98e827a0f13a088 270594.pdf 0f2563cd72563067576c9227133fe973d202f040f5d9b332c141e76188dfbbf9 270594.pdf Title: Novel Targeting of DNA Methyltransferase Activity Inhibits Ewing Sarcoma Cell Proliferation and Enhances Tumor Cell Sensitivity to DNA Damaging Drugs by Activating the DNA Damage Response Subject: DNA methylation is an important component of the epigenetic machinery that regulates the malignancy of Ewing sarcoma (EWS), the second most common primary bone tumor in children and adolescents. Keywords: ewing sarcoma, epigenetic therapies, DNA methylation, DNMT inhibitors, DNA damage, Drug synergism, doxorubicin, PARP inhibitors Author: Camilla Cristalli Creator: Arbortext Advanced Print Publisher 10.0.1306/W Unicode Producer: Acrobat Distiller 7.0 (Windows) CreationDate: Sun May 29 00:56:38 2022 CEST ModDate: Mon May 30 04:00:51 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 779.528 pts Page rot: 0 File size: 12600865 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FJAAOH+AdvOT34fe1490.B Type 1C WinAnsi yes yes no 580 0 FJAAOI+AdvOT01861455.I Type 1C WinAnsi yes yes no 581 0 FJAAOJ+AdvOT1deab444.I Type 1C WinAnsi yes yes no 582 0 FJAAPK+AdvPSA323 Type 1C WinAnsi yes yes no 583 0 FJAAPL+AdvOT6e5d2ec0 Type 1C WinAnsi yes yes no 584 0 FJAAPM+AdvOT6e5d2ec0+fb Type 1C Custom yes yes yes 590 0 FJAAPN+AdvOT3f84ef53 Type 1C WinAnsi yes yes no 591 0 FJABAO+AdvOT6601a1b9.BI Type 1C WinAnsi yes yes no 592 0 FJABGA+AdvOT7d6df7ab.I Type 1C WinAnsi yes yes no 341 0 FJABGB+AdvOTb65e897d.B Type 1C WinAnsi yes yes no 342 0 FJABHB+AdvOT94be8fa4.B Type 1C WinAnsi yes yes no 343 0 FJABEN+AdvOT1ef757c0 Type 1C WinAnsi yes yes no 345 0 FJABEO+AdvOT1ef757c0+fb Type 1C Custom yes yes yes 344 0 FJABFP+AdvOT1ef757c0+20 Type 1C Custom yes yes yes 338 0 FJAJCP+HelveticaNeueLTStd-Bd Type 1C WinAnsi yes yes no 357 0 FJAJHO+AdvOT6e5d2ec0+20 Type 1C WinAnsi yes yes no 369 0 FJANOD+AdvOTd877c31c+20 Type 1C Custom yes yes yes 374 0 FJBDPM+AdvOT1ef757c0+22 Type 1C Custom yes yes no 380 0 FJBDPN+AdvOT34fe1490.B+fb Type 1C Custom yes yes yes 376 0 FJBDPO+AdvOTd877c31c Type 1C WinAnsi yes yes no 375 0 FJBMHH+AdvTT58d178b9+03 Type 1C Custom yes yes yes 382 0 FJBMII+AdvOT1ef757c0+01 Type 1C MacRoman yes yes no 381 0 FJBMKI+AdvOTb65e897d.B+fb Type 1C Custom yes yes yes 384 0 FJBMKJ+AdvOTb65e897d.B+20 Type 1C WinAnsi yes yes no 383 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-03-08 02:42:41 CET RepresentationInformation: 270594.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-07 16:20:16 CET Size: 12600865 Format: PDF Version: 1.4 Status: Well-Formed, but not valid SignatureMatches: PDF-hul ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B10' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B11' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B12' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B14' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B15' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B17' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B14' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B18' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B19' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B21' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B22' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B23' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B24' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B25' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B26' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B27' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B29' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B30' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B31' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B30' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B32' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B33' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B34' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B37' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B38' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B35' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B37' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B39' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B40' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B41' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B42' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B43' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B44' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B45' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B46' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B47' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B12' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B13' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B21' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B48' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B49' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B39' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B50' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B34' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B51' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B53' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B54' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B52' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B55' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B56' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B34' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B57' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B51' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B53' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B36' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B37' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B58' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B59' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B60' cannot be found Offset: 12572187 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'B61' cannot be found Offset: 12572187 MIMEtype: application/pdf PDFMetadata: Objects: 659 FreeObjects: 1 IncrementalUpdates: 2 DocumentCatalog: PageLayout: SinglePage PageMode: UseOutlines Outlines: Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Children: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Children: Item: Title: The DNMT1 MC3343 Inhibitor Synergistically Increases the Cytotoxicity of Doxorubicin and PARPi in EWS Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: DNMTi MC3343 Treatment Results in Reduced Proliferation of EWS Cells and Induction of a Genotoxic Stress Response Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: The DNMT1 MC3343 Inhibitor Synergistically Increases the Cytotoxicity of Doxorubicin and PARPi in EWS Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Children: Item: Title: Chemicals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: DNMT Activity Assay in a Cell Context Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Cells Lines Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: Cell Treatments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: Flow Cytometry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: DNA Extraction and Methylation Profiling Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Item: Title: DNA Methylation Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: Immunofluorescence Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: Western Blotting Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Item: Title: Data Availability Statement Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Item: Title: Ethics Statement Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Item: Title: Author Contributions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b Item: Title: Funding Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b Item: Title: Acknowledgments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31 Item: Title: Supplementary Material Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@b7dd107 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@42eca56e Info: Title: Novel Targeting of DNA Methyltransferase Activity Inhibits Ewing Sarcoma Cell Proliferation and Enhances Tumor Cell Sensitivity to DNA Damaging Drugs by Activating the DNA Damage Response Author: Camilla Cristalli Subject: DNA methylation is an important component of the epigenetic machinery that regulates the malignancy of Ewing sarcoma (EWS), the second most common primary bone tumor in children and adolescents. Keywords: ewing sarcoma, epigenetic therapies, DNA methylation, DNMT inhibitors, DNA damage, Drug synergism, doxorubicin, PARP inhibitors Creator: Arbortext Advanced Print Publisher 10.0.1306/W Unicode Producer: Acrobat Distiller 7.0 (Windows) CreationDate: Sun May 29 00:56:38 CEST 2022 ModDate: Mon May 30 04:00:51 CEST 2022 ID: 0x9c745c20d744817e0ed350ba0d976972, 0xcce4355ded65034f8d67735df81c753f Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1292 ImageHeight: 626 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 626 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 647 ImageHeight: 1249 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1291 ImageHeight: 626 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 647 ImageHeight: 1248 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1292 ImageHeight: 625 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1292 ImageHeight: 625 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1292 ImageHeight: 625 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1292 ImageHeight: 625 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1292 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 647 ImageHeight: 1248 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1292 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1292 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1291 ImageHeight: 625 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 2559 ImageHeight: 3161 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1219 ImageHeight: 643 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1219 ImageHeight: 643 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1219 ImageHeight: 643 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1219 ImageHeight: 643 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1219 ImageHeight: 643 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1219 ImageHeight: 643 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1219 ImageHeight: 643 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1219 ImageHeight: 643 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 2436 ImageHeight: 322 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/png ImageWidth: 3010 ImageHeight: 1761 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 3020 ImageHeight: 2403 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/png ImageWidth: 3005 ImageHeight: 3589 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Fonts: Type1: Font: BaseFont: FJBMKI+AdvOTb65e897d.B+fb FontSubset: true FirstChar: 1 LastChar: 1 FontDescriptor: FontName: FJBMKI+AdvOTb65e897d.B+fb Flags: Symbolic FontBBox: 0, -10, 843, 697 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: FJAAOH+AdvOT34fe1490.B FontSubset: true FirstChar: 35 LastChar: 124 FontDescriptor: FontName: FJAAOH+AdvOT34fe1490.B Flags: Nonsymbolic FontBBox: -52, -208, 937, 968 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJAAOI+AdvOT01861455.I FontSubset: true FirstChar: 42 LastChar: 241 FontDescriptor: FontName: FJAAOI+AdvOT01861455.I Flags: Nonsymbolic FontBBox: -125, -208, 1000, 937 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJAJCP+HelveticaNeueLTStd-Bd FontSubset: true FirstChar: 65 LastChar: 68 FontDescriptor: FontName: FJAJCP+HelveticaNeueLTStd-Bd Flags: Nonsymbolic, ForceBold FontBBox: -166, -218, 1078, 975 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJAAOJ+AdvOT1deab444.I FontSubset: true FirstChar: 37 LastChar: 243 FontDescriptor: FontName: FJAAOJ+AdvOT1deab444.I Flags: Nonsymbolic FontBBox: -135, -208, 968, 947 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJAAPK+AdvPSA323 FontSubset: true FirstChar: 180 LastChar: 184 FontDescriptor: FontName: FJAAPK+AdvPSA323 Flags: Nonsymbolic FontBBox: -156, -239, 1104, 770 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJAAPL+AdvOT6e5d2ec0 FontSubset: true FirstChar: 35 LastChar: 181 FontDescriptor: FontName: FJAAPL+AdvOT6e5d2ec0 Flags: Nonsymbolic FontBBox: -62, -208, 895, 958 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJAAPM+AdvOT6e5d2ec0+fb FontSubset: true FirstChar: 1 LastChar: 3 FontDescriptor: FontName: FJAAPM+AdvOT6e5d2ec0+fb Flags: Symbolic FontBBox: 0, 0, 500, 708 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: FJAAPN+AdvOT3f84ef53 FontSubset: true FirstChar: 103 LastChar: 109 FontDescriptor: FontName: FJAAPN+AdvOT3f84ef53 Flags: Nonsymbolic FontBBox: -177, -291, 1083, 1000 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJABAO+AdvOT6601a1b9.BI FontSubset: true FirstChar: 42 LastChar: 121 FontDescriptor: FontName: FJABAO+AdvOT6601a1b9.BI Flags: Nonsymbolic FontBBox: -125, -208, 1020, 968 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJAJHO+AdvOT6e5d2ec0+20 FontSubset: true FirstChar: 150 LastChar: 150 FontDescriptor: FontName: FJAJHO+AdvOT6e5d2ec0+20 Flags: Nonsymbolic FontBBox: -156, -145, 1041, 718 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJABFP+AdvOT1ef757c0+20 FontSubset: true FirstChar: 2 LastChar: 150 FontDescriptor: FontName: FJABFP+AdvOT1ef757c0+20 Flags: Symbolic FontBBox: -135, -187, 1010, 833 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: FJABGA+AdvOT7d6df7ab.I FontSubset: true FirstChar: 40 LastChar: 241 FontDescriptor: FontName: FJABGA+AdvOT7d6df7ab.I Flags: Nonsymbolic FontBBox: -135, -250, 1000, 854 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJABGB+AdvOTb65e897d.B FontSubset: true FirstChar: 44 LastChar: 121 FontDescriptor: FontName: FJABGB+AdvOTb65e897d.B Flags: Serif, Nonsymbolic FontBBox: -20, -250, 968, 854 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJANOD+AdvOTd877c31c+20 FontSubset: true FirstChar: 1 LastChar: 1 FontDescriptor: FontName: FJANOD+AdvOTd877c31c+20 Flags: Symbolic FontBBox: -177, -333, 2000, 1020 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: FJABHB+AdvOT94be8fa4.B FontSubset: true FirstChar: 109 LastChar: 109 FontDescriptor: FontName: FJABHB+AdvOT94be8fa4.B Flags: Nonsymbolic FontBBox: -197, -291, 1104, 1000 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJBDPO+AdvOTd877c31c FontSubset: true FirstChar: 174 LastChar: 174 FontDescriptor: FontName: FJBDPO+AdvOTd877c31c Flags: Nonsymbolic FontBBox: -62, -208, 927, 958 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJABEO+AdvOT1ef757c0+fb FontSubset: true FirstChar: 1 LastChar: 3 FontDescriptor: FontName: FJABEO+AdvOT1ef757c0+fb Flags: Symbolic FontBBox: 0, -10, 781, 708 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: FJBDPN+AdvOT34fe1490.B+fb FontSubset: true FirstChar: 1 LastChar: 3 FontDescriptor: FontName: FJBDPN+AdvOT34fe1490.B+fb Flags: Symbolic FontBBox: 0, 0, 552, 708 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: FJABEN+AdvOT1ef757c0 FontSubset: true FirstChar: 35 LastChar: 252 FontDescriptor: FontName: FJABEN+AdvOT1ef757c0 Flags: Serif, Nonsymbolic FontBBox: -20, -250, 947, 854 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: FJBDPM+AdvOT1ef757c0+22 FontSubset: true FirstChar: 21 LastChar: 21 FontDescriptor: FontName: FJBDPM+AdvOT1ef757c0+22 Flags: Nonsymbolic FontBBox: -135, -166, 697, 916 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true Font: BaseFont: FJBMII+AdvOT1ef757c0+01 FontSubset: true FirstChar: 245 LastChar: 245 FontDescriptor: FontName: FJBMII+AdvOT1ef757c0+01 Flags: Serif, Nonsymbolic FontBBox: -20, -250, 947, 854 FontFile3: true Encoding: MacRomanEncoding Font: BaseFont: FJBMHH+AdvTT58d178b9+03 FontSubset: true FirstChar: 0 LastChar: 0 FontDescriptor: FontName: FJBMHH+AdvTT58d178b9+03 Flags: Symbolic FontBBox: -645, -354, 916, 895 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: FJBMKJ+AdvOTb65e897d.B+20 FontSubset: true FirstChar: 146 LastChar: 146 FontDescriptor: FontName: FJBMKJ+AdvOTb65e897d.B+20 Flags: Nonsymbolic FontBBox: -125, -177, 1052, 822 FontFile3: true Encoding: WinAnsiEncoding XMP: Acrobat Distiller 7.0 (Windows) ewing sarcoma, epigenetic therapies, DNA methylation, DNMT inhibitors, DNA damage, Drug synergism, doxorubicin, PARP inhibitors 2022-05-30T10:00:51+08:00 2022-05-29T06:56:38+08:00 Arbortext Advanced Print Publisher 10.0.1306/W Unicode 2022-05-30T10:00:51+08:00 application/pdf Novel Targeting of DNA Methyltransferase Activity Inhibits Ewing Sarcoma Cell Proliferation and Enhances Tumor Cell Sensitivity to DNA Damaging Drugs by Activating the DNA Damage Response Camilla Cristalli Maria Cristina Manara Sergio Valente Evelin Pellegrini Alberto Bavelloni Alessandra De Feo William Blalock Elisabetta Di Bello David Piñeyro Angelika Merkel Manel Esteller Oscar M. Tirado Antonello Mai Katia Scotlandi DNA methylation is an important component of the epigenetic machinery that regulates the malignancy of Ewing sarcoma (EWS), the second most common primary bone tumor in children and adolescents. ewing sarcoma epigenetic therapies DNA methylation DNMT inhibitors DNA damage Drug synergism doxorubicin PARP inhibitors uuid:cac2c21b-4efd-4738-bfdb-3bfe41151aa0 uuid:503cd14e-a41a-4e81-a067-359b4d3a37a8 Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 175, 591, 410, 612 Annotation: Subtype: Link Rect: 175, 568, 512, 589 Annotation: Subtype: Link Rect: 175, 545, 547, 566 Annotation: Subtype: Link Rect: 175, 522, 521, 543 Annotation: Subtype: Link Rect: 175, 499, 529, 520 Annotation: Subtype: Link Rect: 175, 476, 453, 497 Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Annotation: Subtype: Link Rect: 87, 474, 158, 482 Annotation: Subtype: Link Rect: 98, 325, 158, 332 Annotation: Subtype: Link Rect: 98, 305, 158, 312 Annotation: Subtype: Link Rect: 58, 64, 158, 71 Annotation: Subtype: Link Rect: 475, 736, 549, 743 Annotation: Subtype: Link Rect: 477, 728, 549, 735 Annotation: Subtype: Link Rect: 450, 720, 549, 727 Annotation: Subtype: Link Rect: 45, 726, 236, 742 Annotation: Subtype: Link Rect: 521, 678, 549, 706 Page: Label: 2 Annotations: Annotation: Subtype: Link Rect: 185, 594, 189, 603 Destination: 229 Annotation: Subtype: Link Rect: 194, 594, 198, 603 Destination: 229 Annotation: Subtype: Link Rect: 167, 513, 171, 523 Destination: 229 Annotation: Subtype: Link Rect: 192, 502, 197, 511 Destination: 229 Annotation: Subtype: Link Rect: 202, 502, 207, 511 Destination: 229 Annotation: Subtype: Link Rect: 112, 490, 117, 500 Destination: 229 Annotation: Subtype: Link Rect: 238, 479, 242, 488 Destination: 229 Annotation: Subtype: Link Rect: 113, 444, 122, 454 Destination: null Annotation: Subtype: Link Rect: 126, 444, 135, 454 Destination: null Annotation: Subtype: Link Rect: 216, 410, 225, 419 Destination: null Annotation: Subtype: Link Rect: 229, 410, 238, 419 Destination: null Annotation: Subtype: Link Rect: 132, 352, 140, 362 Destination: null Annotation: Subtype: Link Rect: 145, 352, 154, 362 Destination: null Annotation: Subtype: Link Rect: 92, 341, 101, 350 Destination: null Annotation: Subtype: Link Rect: 105, 341, 114, 350 Destination: null Annotation: Subtype: Link Rect: 255, 341, 259, 350 Destination: 229 Annotation: Subtype: Link Rect: 263, 341, 272, 350 Destination: null Annotation: Subtype: Link Rect: 277, 341, 285, 350 Destination: null Annotation: Subtype: Link Rect: 179, 329, 188, 339 Destination: null Annotation: Subtype: Link Rect: 194, 329, 202, 339 Destination: null Annotation: Subtype: Link Rect: 48, 295, 57, 304 Destination: null Annotation: Subtype: Link Rect: 63, 295, 72, 304 Destination: null Annotation: Subtype: Link Rect: 205, 283, 214, 293 Destination: null Annotation: Subtype: Link Rect: 177, 272, 181, 281 Destination: 229 Annotation: Subtype: Link Rect: 188, 272, 196, 281 Destination: null Annotation: Subtype: Link Rect: 201, 272, 210, 281 Destination: null Annotation: Subtype: Link Rect: 213, 237, 221, 247 Destination: null Annotation: Subtype: Link Rect: 226, 237, 235, 247 Destination: null Annotation: Subtype: Link Rect: 108, 180, 117, 189 Destination: null Annotation: Subtype: Link Rect: 116, 157, 125, 166 Destination: null Annotation: Subtype: Link Rect: 132, 157, 140, 166 Destination: null Annotation: Subtype: Link Rect: 139, 111, 148, 120 Destination: null Annotation: Subtype: Link Rect: 153, 111, 161, 120 Destination: null Annotation: Subtype: Link Rect: 493, 696, 501, 706 Destination: null Annotation: Subtype: Link Rect: 405, 650, 414, 660 Destination: null Annotation: Subtype: Link Rect: 421, 650, 430, 660 Destination: null Annotation: Subtype: Link Rect: 418, 426, 446, 435 Destination: 1 Annotation: Subtype: Link Rect: 412, 403, 450, 412 Destination: 82 Annotation: Subtype: Link Rect: 502, 357, 544, 366 Destination: 82 Annotation: Subtype: Link Rect: 486, 265, 525, 274 Destination: 82 Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 3 Annotations: Annotation: Subtype: Link Rect: 251, 673, 260, 683 Destination: null Annotation: Subtype: Link Rect: 167, 567, 177, 577 Destination: null Annotation: Subtype: Link Rect: 182, 567, 191, 577 Destination: null Annotation: Subtype: Link Rect: 48, 498, 82, 508 Destination: 138 Annotation: Subtype: Link Rect: 105, 418, 115, 427 Destination: null Annotation: Subtype: Link Rect: 48, 360, 83, 370 Destination: 154 Annotation: Subtype: Link Rect: 104, 360, 208, 370 Destination: 218 Annotation: Subtype: Link Rect: 48, 303, 58, 312 Destination: null Annotation: Subtype: Link Rect: 67, 303, 123, 312 Destination: 177 Annotation: Subtype: Link Rect: 226, 188, 268, 197 Destination: 191 Annotation: Subtype: Link Rect: 115, 165, 155, 174 Destination: 191 Annotation: Subtype: Link Rect: 166, 107, 175, 117 Destination: null Annotation: Subtype: Link Rect: 377, 623, 386, 633 Destination: null Annotation: Subtype: Link Rect: 492, 612, 503, 621 Destination: null Annotation: Subtype: Link Rect: 511, 612, 521, 621 Destination: null Annotation: Subtype: Link Rect: 503, 589, 544, 598 Destination: 207 Annotation: Subtype: Link Rect: 309, 566, 348, 575 Destination: 207 Annotation: Subtype: Link Rect: 352, 543, 408, 552 Destination: 207 Annotation: Subtype: Link Rect: 309, 406, 319, 415 Destination: null Annotation: Subtype: Link Rect: 326, 406, 335, 415 Destination: null Annotation: Subtype: Link Rect: 462, 348, 466, 358 Destination: 229 Annotation: Subtype: Link Rect: 360, 314, 370, 323 Destination: null Annotation: Subtype: Link Rect: 374, 314, 383, 323 Destination: null Annotation: Subtype: Link Rect: 387, 314, 396, 323 Destination: null Annotation: Subtype: Link Rect: 534, 268, 544, 277 Destination: null Annotation: Subtype: Link Rect: 453, 199, 462, 208 Destination: null Annotation: Subtype: Link Rect: 493, 72, 502, 82 Destination: null Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 4 Annotations: Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 5 Annotations: Annotation: Subtype: Link Rect: 208, 213, 217, 223 Destination: null Annotation: Subtype: Link Rect: 222, 213, 231, 223 Destination: null Annotation: Subtype: Link Rect: 263, 179, 272, 188 Destination: null Annotation: Subtype: Link Rect: 118, 75, 127, 85 Destination: null Annotation: Subtype: Link Rect: 463, 248, 468, 257 Destination: 229 Annotation: Subtype: Link Rect: 460, 167, 469, 177 Destination: null Annotation: Subtype: Link Rect: 535, 156, 544, 165 Destination: null Annotation: Subtype: Link Rect: 453, 98, 462, 108 Destination: null Annotation: Subtype: Link Rect: 375, 64, 384, 73 Destination: null Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 6 Annotations: Annotation: Subtype: Link Rect: 175, 179, 184, 189 Destination: null Annotation: Subtype: Link Rect: 189, 179, 198, 189 Destination: null Annotation: Subtype: Link Rect: 494, 214, 504, 223 Destination: null Annotation: Subtype: Link Rect: 510, 214, 519, 223 Destination: null Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 7 Annotations: Annotation: Subtype: Link Rect: 134, 237, 144, 247 Destination: null Annotation: Subtype: Link Rect: 151, 237, 160, 247 Destination: null Annotation: Subtype: Link Rect: 244, 214, 253, 224 Destination: null Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 8 Annotations: Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 9 Annotations: Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 10 Annotations: Annotation: Subtype: Link Rect: 404, 673, 413, 683 Destination: null Annotation: Subtype: Link Rect: 523, 572, 549, 581 Annotation: Subtype: Link Rect: 306, 560, 514, 570 Annotation: Subtype: Link Rect: 306, 77, 549, 86 Annotation: Subtype: Link Rect: 306, 65, 408, 75 Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 11 Annotations: Annotation: Subtype: Link Rect: 263, 669, 289, 677 Annotation: Subtype: Link Rect: 58, 660, 91, 667 Annotation: Subtype: Link Rect: 106, 612, 186, 620 Annotation: Subtype: Link Rect: 263, 565, 289, 572 Annotation: Subtype: Link Rect: 58, 555, 100, 563 Annotation: Subtype: Link Rect: 240, 536, 289, 544 Annotation: Subtype: Link Rect: 58, 527, 92, 534 Annotation: Subtype: Link Rect: 190, 498, 264, 506 Annotation: Subtype: Link Rect: 106, 460, 202, 468 Annotation: Subtype: Link Rect: 159, 432, 255, 439 Annotation: Subtype: Link Rect: 263, 413, 289, 420 Annotation: Subtype: Link Rect: 58, 403, 119, 411 Annotation: Subtype: Link Rect: 208, 375, 260, 382 Annotation: Subtype: Link Rect: 109, 356, 188, 363 Annotation: Subtype: Link Rect: 262, 327, 289, 335 Annotation: Subtype: Link Rect: 57, 318, 125, 325 Annotation: Subtype: Link Rect: 127, 280, 207, 287 Annotation: Subtype: Link Rect: 193, 242, 277, 249 Annotation: Subtype: Link Rect: 82, 204, 179, 211 Annotation: Subtype: Link Rect: 239, 175, 289, 183 Annotation: Subtype: Link Rect: 57, 166, 96, 173 Annotation: Subtype: Link Rect: 202, 128, 289, 135 Annotation: Subtype: Link Rect: 57, 118, 72, 126 Annotation: Subtype: Link Rect: 163, 80, 246, 88 Annotation: Subtype: Link Rect: 394, 678, 501, 686 Annotation: Subtype: Link Rect: 332, 640, 388, 648 Annotation: Subtype: Link Rect: 363, 612, 427, 619 Annotation: Subtype: Link Rect: 388, 574, 477, 581 Annotation: Subtype: Link Rect: 370, 536, 443, 543 Annotation: Subtype: Link Rect: 332, 488, 412, 496 Annotation: Subtype: Link Rect: 486, 460, 549, 467 Annotation: Subtype: Link Rect: 318, 450, 344, 458 Annotation: Subtype: Link Rect: 522, 431, 549, 439 Annotation: Subtype: Link Rect: 319, 422, 396, 429 Annotation: Subtype: Link Rect: 485, 403, 549, 410 Annotation: Subtype: Link Rect: 318, 393, 339, 401 Annotation: Subtype: Link Rect: 423, 355, 487, 363 Annotation: Subtype: Link Rect: 430, 327, 486, 334 Annotation: Subtype: Link Rect: 484, 298, 538, 306 Annotation: Subtype: Link Rect: 333, 270, 404, 277 Annotation: Subtype: Link Rect: 412, 241, 478, 249 Annotation: Subtype: Link Rect: 470, 222, 549, 230 Annotation: Subtype: Link Rect: 318, 213, 329, 220 Annotation: Subtype: Link Rect: 388, 194, 501, 201 Annotation: Subtype: Link Rect: 524, 165, 549, 173 Annotation: Subtype: Link Rect: 318, 156, 394, 163 Annotation: Subtype: Link Rect: 332, 118, 419, 125 Annotation: Subtype: Link Rect: 366, 80, 425, 87 Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Page: Label: 12 Annotations: Annotation: Subtype: Link Rect: 176, 691, 253, 698 Annotation: Subtype: Link Rect: 207, 662, 288, 670 Annotation: Subtype: Link Rect: 262, 643, 289, 651 Annotation: Subtype: Link Rect: 57, 634, 120, 641 Annotation: Subtype: Link Rect: 158, 605, 234, 613 Annotation: Subtype: Link Rect: 131, 577, 199, 584 Annotation: Subtype: Link Rect: 138, 529, 216, 537 Annotation: Subtype: Link Rect: 131, 501, 183, 508 Annotation: Subtype: Link Rect: 169, 472, 269, 480 Annotation: Subtype: Link Rect: 259, 453, 289, 461 Annotation: Subtype: Link Rect: 57, 444, 147, 451 Annotation: Subtype: Link Rect: 109, 415, 210, 423 Annotation: Subtype: Link Rect: 225, 396, 289, 404 Annotation: Subtype: Link Rect: 57, 387, 87, 394 Annotation: Subtype: Link Rect: 111, 349, 186, 356 Annotation: Subtype: Link Rect: 127, 320, 211, 328 Annotation: Subtype: Link Rect: 191, 292, 260, 299 Annotation: Subtype: Link Rect: 71, 254, 146, 261 Annotation: Subtype: Link Rect: 109, 225, 180, 233 Annotation: Subtype: Link Rect: 417, 691, 465, 698 Annotation: Subtype: Link Rect: 332, 653, 407, 660 Annotation: Subtype: Link Rect: 332, 615, 388, 622 Annotation: Subtype: Link Rect: 332, 577, 450, 584 Annotation: Subtype: Link Rect: 443, 539, 520, 546 Annotation: Subtype: Link Rect: 332, 501, 409, 508 Annotation: Subtype: Link Rect: 388, 463, 488, 470 Annotation: Subtype: Link Rect: 359, 425, 445, 432 Annotation: Subtype: Link Rect: 433, 263, 549, 271 Annotation: Subtype: Link Rect: 306, 254, 330, 261 Annotation: Subtype: Link Rect: 45, 29, 122, 36 Annotation: Subtype: Link Rect: 131, 29, 189, 36 Annotation: Subtype: Link Rect: 427, 29, 549, 36 Checksum: 599794de Type: CRC32 Checksum: 0ccccbca4fec2f27cf61d0e4d174378a Type: MD5 Checksum: 6a3a26e9998cf47832ca843ed98e827a0f13a088 Type: SHA-1