4eaab3257dd0b379c926efd4026417c4 pmc_31998851.pdf f316c576bbc3dcd006d2f9ba9178463cb8bc15a6 pmc_31998851.pdf 2f1c1685a4c8ea8fafdfa4c607d91bed966ad805c84488def371723a06b608dd pmc_31998851.pdf Title: Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes Subject: JACC: Basic to Translational Science, 4 (2019) 831-840. doi:10.1016/j.jacbts.2019.07.010 Author: Oriol Iborra-Egea MSc Creator: Elsevier Producer: Acrobat Distiller 8.1.0 (Windows) CreationDate: Mon Nov 11 23:21:25 2019 CET ModDate: Mon Nov 11 23:22:06 2019 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 576 x 773.972 pts Page rot: 0 File size: 1191861 bytes Optimized: yes PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GELJKE+AdvPSSym Type 1C WinAnsi yes yes no 727 0 GELIGA+AdvOT5b669f61 Type 1C WinAnsi yes yes no 690 0 GELIGB+AdvOTa2a4c9ce Type 1C WinAnsi yes yes no 692 0 GELIGC+AdvOTa2a4c9ce+fb Type 1C Custom yes yes yes 697 0 GELIGD+AdvOTe81213fa Type 1C WinAnsi yes yes no 699 0 GELJGO+AdvOT2986fa51 Type 1C WinAnsi yes yes no 703 0 GELJHO+AdvOT2986fa51+20 Type 1C WinAnsi yes yes no 705 0 GELJHP+AdvOT8f503d4a Type 1C WinAnsi yes yes no 716 0 GELJIA+AdvP4C4E74 Type 1C Custom yes yes yes 707 0 GELJIB+AdvOTc3f2c111.B Type 1C WinAnsi yes yes no 709 0 GELJIC+AdvOTc3f2c111.B+fb Type 1C Custom yes yes yes 714 0 GELJID+AdvOT61751f86 Type 1C WinAnsi yes yes no 723 0 GELJME+AdvOT2986fa51+fb Type 1C Custom yes yes yes 390 0 GELJMF+AdvOT78d326c7 Type 1C WinAnsi yes yes no 398 0 GELJOF+AdvOTe81213fa+fb Type 1C Custom yes yes yes 396 0 GELJOG+AdvOTe81213fa+20 Type 1C WinAnsi yes yes no 407 0 GELJPH+AdvOT1a97e067.I Type 1C WinAnsi yes yes no 410 0 GELJPI+AdvOTd9ad3ae4.I Type 1C WinAnsi yes yes no 404 0 GELJPJ+AdvOT61751f86+20 Type 1C WinAnsi yes yes no 405 0 GELKCJ+AdvOTe60b6cd3.B Type 1C WinAnsi yes yes no 417 0 GELLAE+AdvP4C4E51 Type 1C WinAnsi yes yes no 424 0 GELLBF+AdvPS3F4C13 Type 1C WinAnsi yes yes no 427 0 GELLDF+AdvOTe60b6cd3.B+fb Type 1C Custom yes yes yes 433 0 GEMALF+AdvP4C4E59 Type 1C Custom yes yes no 454 0 GEMALG+AdvOTf2345705 Type 1C WinAnsi yes yes no 450 0 GEMALH+AdvOTf2345705+fb Type 1C Custom yes yes yes 455 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-08-10 12:12:31 CEST RepresentationInformation: pmc_31998851.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-03-16 03:54:39 CET Size: 1191861 Format: PDF Version: 1.7 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 'aff10' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib10' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib11' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib12' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib13' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib14' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib16' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'tbl1fnlowast' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib17' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib22' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib23' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib23' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib24' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib24' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib26' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib27' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib27' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'tbl3fnlowast' cannot be found Offset: 1163189 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bib28' cannot be found Offset: 1163189 MIMEtype: application/pdf Profile: Linearized PDF PDFMetadata: Objects: 779 FreeObjects: 1 IncrementalUpdates: 1 DocumentCatalog: PageLayout: SinglePage PageMode: UseOutlines Outlines: Item: Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Children: Item: Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Children: Item: Title: Machine learning in silico analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Children: Item: Title: Molecular characterization of HF and DM pathology and drug treatments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Compilation of transcriptomic data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Generation of mathematical models Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Therapeutic performance mapping system technology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Post-infarct heart failure in VIVO rat model Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Children: Item: Title: Induction of diabetes mellitus in Wistar rats Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: Induction of myocardial infarction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Experimental design and study protocol Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: Real time PCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: Data integration and statistical analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Children: Item: Title: Empagliflozin acts upon a specific HF-related pathological signature Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: ANN evaluates the relationships among protein sets inside the network, providing a predictive score Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: NHE1 is responsible for the cardiac effects of empagliflozin in HFrEF with or without DM Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Children: Item: Title: Direct empagliflozin-driven NHE1 blockade ameliorates cardiomyocyte cell death Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Children: Item: Title: Study limitations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b Item: Title: Acknowledgments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31 Info: Title: Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes Author: Oriol Iborra-Egea MSc Subject: JACC: Basic to Translational Science, 4 (2019) 831-840. doi:10.1016/j.jacbts.2019.07.010 Creator: Elsevier Producer: Acrobat Distiller 8.1.0 (Windows) CreationDate: Mon Nov 11 23:51:25 CET 2019 ModDate: Mon Nov 11 23:52:06 CET 2019 ID: 0xe9cd93a78a3d47667cdddb048e92d616, 0x0487e80ec49ed6439924c2efdc004a92 Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1046 ImageHeight: 912 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1595 ImageHeight: 1107 ColorSpace: black is zero BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1968 ImageHeight: 1143 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1968 ImageHeight: 1193 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Fonts: Type1: Font: BaseFont: GELJHO+AdvOT2986fa51+20 FontSubset: true FirstChar: 146 LastChar: 150 FontDescriptor: FontName: GELJHO+AdvOT2986fa51+20 Flags: Nonsymbolic FontBBox: -145, -114, 1270, 739 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GEMALG+AdvOTf2345705 FontSubset: true FirstChar: 44 LastChar: 122 FontDescriptor: FontName: GEMALG+AdvOTf2345705 Flags: Nonsymbolic FontBBox: -62, -239, 895, 979 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJIA+AdvP4C4E74 FontSubset: true FirstChar: 1 LastChar: 254 FontDescriptor: FontName: GELJIA+AdvP4C4E74 Flags: Symbolic FontBBox: -20, -958, 1114, 770 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GELJIB+AdvOTc3f2c111.B FontSubset: true FirstChar: 37 LastChar: 122 FontDescriptor: FontName: GELJIB+AdvOTc3f2c111.B Flags: Nonsymbolic FontBBox: -52, -250, 927, 1000 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJME+AdvOT2986fa51+fb FontSubset: true FirstChar: 1 LastChar: 3 FontDescriptor: FontName: GELJME+AdvOT2986fa51+fb Flags: Symbolic FontBBox: 19, 0, 916, 770 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GEMALF+AdvP4C4E59 FontSubset: true FirstChar: 1 LastChar: 1 FontDescriptor: FontName: GEMALF+AdvP4C4E59 Flags: Symbolic FontBBox: -31, -250, 1000, 750 FontFile3: true EncodingDictionary: Differences: true Font: BaseFont: GEMALH+AdvOTf2345705+fb FontSubset: true FirstChar: 1 LastChar: 1 FontDescriptor: FontName: GEMALH+AdvOTf2345705+fb Flags: Symbolic FontBBox: 9, 0, 906, 770 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GELJIC+AdvOTc3f2c111.B+fb FontSubset: true FirstChar: 1 LastChar: 3 FontDescriptor: FontName: GELJIC+AdvOTc3f2c111.B+fb Flags: Symbolic FontBBox: 19, 0, 937, 770 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GELJHP+AdvOT8f503d4a FontSubset: true FirstChar: 45 LastChar: 115 FontDescriptor: FontName: GELJHP+AdvOT8f503d4a Flags: Nonsymbolic FontBBox: -52, -197, 1093, 927 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJOF+AdvOTe81213fa+fb FontSubset: true FirstChar: 1 LastChar: 3 FontDescriptor: FontName: GELJOF+AdvOTe81213fa+fb Flags: Symbolic FontBBox: 19, 0, 947, 791 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GELJMF+AdvOT78d326c7 FontSubset: true FirstChar: 66 LastChar: 66 FontDescriptor: FontName: GELJMF+AdvOT78d326c7 Flags: Nonsymbolic FontBBox: -41, -260, 979, 833 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJID+AdvOT61751f86 FontSubset: true FirstChar: 40 LastChar: 121 FontDescriptor: FontName: GELJID+AdvOT61751f86 Flags: Nonsymbolic FontBBox: -10, -197, 916, 875 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJPI+AdvOTd9ad3ae4.I FontSubset: true FirstChar: 49 LastChar: 116 FontDescriptor: FontName: GELJPI+AdvOTd9ad3ae4.I Flags: Nonsymbolic FontBBox: -135, -239, 927, 979 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJPJ+AdvOT61751f86+20 FontSubset: true FirstChar: 150 LastChar: 150 FontDescriptor: FontName: GELJPJ+AdvOT61751f86+20 Flags: Nonsymbolic FontBBox: -187, -197, 1031, 812 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJKE+AdvPSSym FontSubset: true FirstChar: 170 LastChar: 170 FontDescriptor: FontName: GELJKE+AdvPSSym Flags: Nonsymbolic FontBBox: -177, -291, 1083, 1010 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJOG+AdvOTe81213fa+20 FontSubset: true FirstChar: 146 LastChar: 150 FontDescriptor: FontName: GELJOG+AdvOTe81213fa+20 Flags: Nonsymbolic FontBBox: -187, -125, 1250, 729 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJPH+AdvOT1a97e067.I FontSubset: true FirstChar: 51 LastChar: 116 FontDescriptor: FontName: GELJPH+AdvOT1a97e067.I Flags: Serif, Nonsymbolic FontBBox: -156, -239, 1062, 1010 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELKCJ+AdvOTe60b6cd3.B FontSubset: true FirstChar: 40 LastChar: 122 FontDescriptor: FontName: GELKCJ+AdvOTe60b6cd3.B Flags: Nonsymbolic FontBBox: -52, -250, 947, 1010 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELLAE+AdvP4C4E51 FontSubset: true FirstChar: 60 LastChar: 62 FontDescriptor: FontName: GELLAE+AdvP4C4E51 Flags: Nonsymbolic FontBBox: -31, -239, 1041, 750 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELLBF+AdvPS3F4C13 FontSubset: true FirstChar: 68 LastChar: 109 FontDescriptor: FontName: GELLBF+AdvPS3F4C13 Flags: Nonsymbolic FontBBox: 0, -291, 875, 697 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELLDF+AdvOTe60b6cd3.B+fb FontSubset: true FirstChar: 1 LastChar: 3 FontDescriptor: FontName: GELLDF+AdvOTe60b6cd3.B+fb Flags: Symbolic FontBBox: 19, 0, 947, 770 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GELIGA+AdvOT5b669f61 FontSubset: true FirstChar: 44 LastChar: 114 FontDescriptor: FontName: GELIGA+AdvOT5b669f61 Flags: Nonsymbolic FontBBox: -41, -197, 1083, 927 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELIGB+AdvOTa2a4c9ce FontSubset: true FirstChar: 65 LastChar: 122 FontDescriptor: FontName: GELIGB+AdvOTa2a4c9ce Flags: Nonsymbolic FontBBox: -20, -197, 1072, 906 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELIGC+AdvOTa2a4c9ce+fb FontSubset: true FirstChar: 1 LastChar: 1 FontDescriptor: FontName: GELIGC+AdvOTa2a4c9ce+fb Flags: Symbolic FontBBox: 0, -197, 958, 791 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GELIGD+AdvOTe81213fa FontSubset: true FirstChar: 37 LastChar: 250 FontDescriptor: FontName: GELIGD+AdvOTe81213fa Flags: Serif, Nonsymbolic FontBBox: -31, -239, 989, 1010 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: GELJGO+AdvOT2986fa51 FontSubset: true FirstChar: 37 LastChar: 252 FontDescriptor: FontName: GELJGO+AdvOT2986fa51 Flags: Nonsymbolic FontBBox: -52, -239, 885, 979 FontFile3: true Encoding: WinAnsiEncoding XMP: application/pdf doi:10.1016/j.jacbts.2019.07.010 Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes Oriol Iborra-Egea MSc Evelyn Santiago-Vacas MD Salva R. Yurista MD Josep Lupón MD PhD Milton Packer MD Stephane Heymans MD Faiez Zannad MD Javed Butler MD Domingo Pascual-Figal MD Antonio Lax PhD Julio Núñez MD PhD Rudolf A. de Boer MD PhD Antoni Bayés-Genís MD PhD empagliflozin heart failure machine learning JACC: Basic to Translational Science, 4 (2019) 831-840. doi:10.1016/j.jacbts.2019.07.010 Elsevier journal JACC: Basic to Translational Science © 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. 2452-302X 4 7 November 2019 831-840 831 840 10.1016/j.jacbts.2019.07.010 https://doi.org/10.1016/j.jacbts.2019.07.010 2010-04-23 true 10.1016/j.jacbts.2019.07.010 elsevier.com sciencedirect.com VoR 6.5 10.1016/j.jacbts.2019.07.010 noindex 2010-04-23 true sciencedirect.com elsevier.com Elsevier 2019-11-12T03:51:25+05:30 2019-11-12T03:52:06+05:30 2019-11-12T03:52:06+05:30 True Acrobat Distiller 8.1.0 (Windows) uuid:e4cd646e-0557-47b6-9786-43028c5fee89 uuid:3396edf1-77fd-47b8-8c0a-3938a61df3fd http://creativecommons.org/licenses/by-nc-nd/4.0/ Pages: Page: Label: 831 Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 198, 512, 201, 519 Destination: 1 Annotation: Subtype: Link Rect: 203, 512, 206, 519 Destination: 1 Annotation: Subtype: Link Rect: 208, 512, 211, 519 Destination: 1 Annotation: Subtype: Link Rect: 316, 512, 319, 519 Destination: 1 Annotation: Subtype: Link Rect: 321, 512, 324, 519 Destination: 1 Annotation: Subtype: Link Rect: 326, 512, 329, 519 Destination: 1 Annotation: Subtype: Link Rect: 410, 512, 413, 519 Destination: 1 Annotation: Subtype: Link Rect: 502, 512, 505, 519 Destination: 1 Annotation: Subtype: Link Rect: 506, 512, 510, 519 Destination: 1 Annotation: Subtype: Link Rect: 512, 512, 514, 519 Destination: 1 Annotation: Subtype: Link Rect: 184, 500, 187, 508 Destination: 1 Annotation: Subtype: Link Rect: 280, 500, 283, 508 Destination: 1 Annotation: Subtype: Link Rect: 354, 500, 357, 508 Destination: 1 Annotation: Subtype: Link Rect: 426, 500, 429, 508 Destination: 1 Annotation: Subtype: Link Rect: 536, 500, 537, 508 Destination: 1 Annotation: Subtype: Link Rect: 180, 488, 182, 496 Destination: 1 Annotation: Subtype: Link Rect: 267, 488, 269, 496 Destination: null Annotation: Subtype: Link Rect: 377, 488, 380, 496 Destination: 1 Annotation: Subtype: Link Rect: 492, 488, 495, 496 Destination: 1 Annotation: Subtype: Link Rect: 497, 488, 500, 496 Destination: 1 Annotation: Subtype: Link Rect: 502, 488, 505, 496 Destination: 1 Annotation: Subtype: Link Rect: 409, 20, 537, 27 Annotation: Subtype: Link Rect: 513, 597, 537, 621 Annotation: Subtype: Link Rect: 202, 703, 364, 708 Page: Label: 832 Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 323, 545, 497, 552 Annotation: Subtype: Link Rect: 273, 477, 283, 485 Destination: 103 Annotation: Subtype: Link Rect: 236, 430, 246, 437 Destination: 103 Annotation: Subtype: Link Rect: 327, 489, 337, 497 Destination: 103 Annotation: Subtype: Link Rect: 443, 466, 461, 473 Destination: 103 Annotation: Subtype: Link Rect: 355, 382, 365, 389 Destination: 103 Annotation: Subtype: Link Rect: 445, 322, 498, 330 Annotation: Subtype: Link Rect: 192, 52, 260, 58 Page: Label: 833 Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 148, 320, 158, 328 Destination: 103 Annotation: Subtype: Link Rect: 126, 273, 137, 280 Destination: 103 Annotation: Subtype: Link Rect: 80, 202, 91, 210 Destination: 103 Annotation: Subtype: Link Rect: 172, 130, 205, 138 Destination: 16 Annotation: Subtype: Link Rect: 343, 79, 373, 87 Destination: 16 Annotation: Subtype: Link Rect: 65, 360, 127, 366 Page: Label: 834 Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 129, 611, 143, 618 Destination: null Annotation: Subtype: Link Rect: 204, 611, 216, 618 Destination: null Annotation: Subtype: Link Rect: 112, 551, 201, 558 Annotation: Subtype: Link Rect: 223, 503, 250, 511 Destination: 16 Annotation: Subtype: Link Rect: 295, 491, 307, 499 Destination: null Annotation: Subtype: Link Rect: 214, 120, 228, 128 Destination: null Annotation: Subtype: Link Rect: 199, 73, 229, 80 Destination: 16 Annotation: Subtype: Link Rect: 327, 646, 352, 654 Destination: null Annotation: Subtype: Link Rect: 330, 575, 361, 582 Destination: 16 Annotation: Subtype: Link Rect: 366, 575, 452, 582 Annotation: Subtype: Link Rect: 469, 539, 499, 547 Destination: 16 Annotation: Subtype: Link Rect: 517, 132, 531, 140 Destination: null Page: Label: 835 Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 157, 132, 241, 140 Annotation: Subtype: Link Rect: 262, 97, 349, 104 Annotation: Subtype: Link Rect: 529, 640, 531, 646 Destination: null Page: Label: 836 Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 159, 447, 186, 455 Destination: 47 Annotation: Subtype: Link Rect: 255, 375, 283, 383 Destination: 56 Annotation: Subtype: Link Rect: 444, 502, 475, 510 Destination: 70 Annotation: Subtype: Link Rect: 480, 502, 534, 510 Annotation: Subtype: Link Rect: 327, 490, 356, 498 Annotation: Subtype: Link Rect: 330, 466, 359, 474 Destination: 80 Annotation: Subtype: Link Rect: 379, 324, 410, 331 Destination: 70 Annotation: Subtype: Link Rect: 386, 61, 421, 68 Destination: 93 Page: Label: 837 Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 73, 218, 106, 226 Destination: 93 Annotation: Subtype: Link Rect: 166, 122, 197, 130 Destination: 70 Annotation: Subtype: Link Rect: 351, 254, 361, 262 Destination: 103 Annotation: Subtype: Link Rect: 260, 62, 284, 70 Destination: null Page: Label: 838 Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 179, 503, 193, 511 Destination: null Annotation: Subtype: Link Rect: 205, 407, 220, 415 Destination: null Annotation: Subtype: Link Rect: 133, 395, 147, 403 Destination: null Annotation: Subtype: Link Rect: 191, 49, 218, 56 Destination: null Annotation: Subtype: Link Rect: 259, 37, 274, 44 Destination: null Annotation: Subtype: Link Rect: 350, 634, 364, 642 Destination: null Annotation: Subtype: Link Rect: 435, 599, 449, 606 Destination: null Annotation: Subtype: Link Rect: 327, 503, 342, 511 Destination: null Annotation: Subtype: Link Rect: 213, 665, 216, 671 Destination: null Page: Label: 839 Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 143, 135, 158, 143 Destination: null Annotation: Subtype: Link Rect: 360, 37, 454, 45 Annotation: Subtype: Link Rect: 158, 319, 182, 326 Destination: 70 Page: Label: 840 Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 115, 477, 243, 483 Annotation: Subtype: Link Rect: 109, 468, 243, 474 Annotation: Subtype: Link Rect: 109, 459, 197, 465 Annotation: Subtype: Link Rect: 116, 447, 243, 453 Annotation: Subtype: Link Rect: 109, 438, 243, 444 Annotation: Subtype: Link Rect: 109, 429, 243, 435 Annotation: Subtype: Link Rect: 109, 420, 206, 426 Annotation: Subtype: Link Rect: 116, 408, 243, 414 Annotation: Subtype: Link Rect: 109, 399, 243, 405 Annotation: Subtype: Link Rect: 109, 390, 243, 396 Annotation: Subtype: Link Rect: 109, 381, 239, 387 Annotation: Subtype: Link Rect: 117, 369, 243, 374 Annotation: Subtype: Link Rect: 109, 360, 243, 366 Annotation: Subtype: Link Rect: 109, 351, 243, 357 Annotation: Subtype: Link Rect: 109, 342, 225, 348 Annotation: Subtype: Link Rect: 116, 329, 243, 335 Annotation: Subtype: Link Rect: 109, 320, 243, 326 Annotation: Subtype: Link Rect: 109, 311, 243, 317 Annotation: Subtype: Link Rect: 109, 302, 243, 308 Annotation: Subtype: Link Rect: 109, 293, 144, 299 Annotation: Subtype: Link Rect: 117, 281, 243, 287 Annotation: Subtype: Link Rect: 109, 272, 243, 278 Annotation: Subtype: Link Rect: 109, 263, 243, 269 Annotation: Subtype: Link Rect: 109, 254, 219, 260 Annotation: Subtype: Link Rect: 116, 242, 243, 248 Annotation: Subtype: Link Rect: 109, 233, 243, 239 Annotation: Subtype: Link Rect: 109, 224, 243, 230 Annotation: Subtype: Link Rect: 109, 215, 151, 221 Annotation: Subtype: Link Rect: 117, 203, 243, 208 Annotation: Subtype: Link Rect: 109, 194, 243, 200 Annotation: Subtype: Link Rect: 109, 185, 243, 191 Annotation: Subtype: Link Rect: 109, 176, 243, 182 Annotation: Subtype: Link Rect: 109, 167, 206, 173 Annotation: Subtype: Link Rect: 117, 154, 243, 160 Annotation: Subtype: Link Rect: 109, 145, 243, 151 Annotation: Subtype: Link Rect: 109, 136, 243, 142 Annotation: Subtype: Link Rect: 109, 127, 243, 133 Annotation: Subtype: Link Rect: 109, 118, 141, 124 Annotation: Subtype: Link Rect: 119, 106, 243, 112 Annotation: Subtype: Link Rect: 109, 97, 243, 103 Annotation: Subtype: Link Rect: 109, 88, 222, 94 Annotation: Subtype: Link Rect: 118, 76, 243, 82 Annotation: Subtype: Link Rect: 109, 67, 243, 73 Annotation: Subtype: Link Rect: 109, 58, 243, 64 Annotation: Subtype: Link Rect: 109, 49, 197, 55 Annotation: Subtype: Link Rect: 264, 477, 388, 483 Annotation: Subtype: Link Rect: 255, 468, 388, 474 Annotation: Subtype: Link Rect: 255, 459, 329, 465 Annotation: Subtype: Link Rect: 264, 447, 388, 453 Annotation: Subtype: Link Rect: 255, 438, 388, 444 Annotation: Subtype: Link Rect: 255, 429, 388, 435 Annotation: Subtype: Link Rect: 255, 420, 360, 426 Annotation: Subtype: Link Rect: 265, 407, 388, 413 Annotation: Subtype: Link Rect: 255, 398, 388, 404 Annotation: Subtype: Link Rect: 255, 389, 388, 395 Annotation: Subtype: Link Rect: 255, 380, 301, 386 Annotation: Subtype: Link Rect: 264, 367, 388, 373 Annotation: Subtype: Link Rect: 255, 358, 388, 364 Annotation: Subtype: Link Rect: 255, 349, 269, 355 Annotation: Subtype: Link Rect: 265, 337, 388, 343 Annotation: Subtype: Link Rect: 255, 328, 388, 334 Annotation: Subtype: Link Rect: 255, 319, 388, 325 Annotation: Subtype: Link Rect: 255, 310, 388, 316 Annotation: Subtype: Link Rect: 255, 301, 388, 307 Annotation: Subtype: Link Rect: 255, 292, 282, 298 Annotation: Subtype: Link Rect: 264, 279, 272, 285 Annotation: Subtype: Link Rect: 275, 279, 388, 285 Annotation: Subtype: Link Rect: 255, 270, 388, 276 Annotation: Subtype: Link Rect: 255, 261, 388, 267 Annotation: Subtype: Link Rect: 255, 252, 388, 258 Annotation: Subtype: Link Rect: 255, 243, 388, 249 Annotation: Subtype: Link Rect: 255, 234, 358, 240 Annotation: Subtype: Link Rect: 265, 222, 388, 228 Annotation: Subtype: Link Rect: 255, 213, 300, 219 Annotation: Subtype: Link Rect: 304, 213, 311, 219 Annotation: Subtype: Link Rect: 315, 213, 388, 219 Annotation: Subtype: Link Rect: 255, 204, 388, 210 Annotation: Subtype: Link Rect: 255, 195, 388, 201 Annotation: Subtype: Link Rect: 255, 186, 310, 192 Annotation: Subtype: Link Rect: 265, 173, 388, 179 Annotation: Subtype: Link Rect: 255, 164, 388, 170 Annotation: Subtype: Link Rect: 255, 155, 289, 161 Annotation: Subtype: Link Rect: 294, 155, 300, 161 Annotation: Subtype: Link Rect: 305, 155, 388, 161 Annotation: Subtype: Link Rect: 255, 146, 300, 152 Annotation: Subtype: Link Rect: 305, 146, 388, 152 Annotation: Subtype: Link Rect: 255, 137, 388, 143 Annotation: Subtype: Link Rect: 255, 128, 388, 134 Annotation: Subtype: Link Rect: 255, 119, 301, 125 Annotation: Subtype: Link Rect: 265, 106, 388, 112 Annotation: Subtype: Link Rect: 255, 97, 330, 103 Annotation: Subtype: Link Rect: 335, 97, 341, 103 Annotation: Subtype: Link Rect: 346, 97, 388, 103 Annotation: Subtype: Link Rect: 255, 89, 388, 95 Annotation: Subtype: Link Rect: 255, 80, 388, 86 Annotation: Subtype: Link Rect: 255, 71, 308, 77 Annotation: Subtype: Link Rect: 264, 58, 373, 64 Annotation: Subtype: Link Rect: 377, 58, 384, 64 Annotation: Subtype: Link Rect: 255, 49, 388, 55 Annotation: Subtype: Link Rect: 400, 477, 534, 483 Annotation: Subtype: Link Rect: 400, 468, 534, 474 Annotation: Subtype: Link Rect: 400, 459, 424, 465 Annotation: Subtype: Link Rect: 410, 447, 534, 453 Annotation: Subtype: Link Rect: 400, 438, 534, 444 Annotation: Subtype: Link Rect: 400, 429, 534, 435 Annotation: Subtype: Link Rect: 400, 420, 417, 426 Annotation: Subtype: Link Rect: 422, 420, 429, 426 Annotation: Subtype: Link Rect: 433, 420, 534, 426 Annotation: Subtype: Link Rect: 400, 411, 408, 417 Annotation: Subtype: Link Rect: 412, 411, 534, 417 Annotation: Subtype: Link Rect: 400, 402, 417, 408 Annotation: Subtype: Link Rect: 410, 390, 534, 396 Annotation: Subtype: Link Rect: 400, 381, 534, 387 Annotation: Subtype: Link Rect: 400, 372, 407, 378 Annotation: Subtype: Link Rect: 412, 372, 518, 378 Annotation: Subtype: Link Rect: 523, 372, 529, 378 Annotation: Subtype: Link Rect: 400, 363, 534, 369 Annotation: Subtype: Link Rect: 400, 354, 429, 360 Annotation: Subtype: Link Rect: 411, 342, 534, 348 Annotation: Subtype: Link Rect: 400, 333, 534, 339 Annotation: Subtype: Link Rect: 400, 324, 534, 330 Annotation: Subtype: Link Rect: 400, 315, 534, 321 Annotation: Subtype: Link Rect: 400, 306, 473, 312 Annotation: Subtype: Link Rect: 410, 293, 534, 299 Annotation: Subtype: Link Rect: 400, 284, 534, 290 Annotation: Subtype: Link Rect: 400, 275, 534, 281 Annotation: Subtype: Link Rect: 400, 266, 534, 272 Annotation: Subtype: Link Rect: 400, 258, 420, 263 Annotation: Subtype: Link Rect: 411, 245, 534, 251 Annotation: Subtype: Link Rect: 400, 236, 534, 242 Annotation: Subtype: Link Rect: 400, 227, 534, 233 Annotation: Subtype: Link Rect: 400, 218, 534, 224 Annotation: Subtype: Link Rect: 400, 209, 456, 215 Annotation: Subtype: Link Rect: 410, 197, 534, 203 Annotation: Subtype: Link Rect: 400, 188, 534, 194 Annotation: Subtype: Link Rect: 400, 179, 534, 185 Annotation: Subtype: Link Rect: 400, 170, 449, 176 Annotation: Subtype: Link Rect: 411, 158, 534, 164 Annotation: Subtype: Link Rect: 400, 149, 534, 155 Annotation: Subtype: Link Rect: 400, 140, 465, 146 Checksum: 75025f80 Type: CRC32 Checksum: 4eaab3257dd0b379c926efd4026417c4 Type: MD5 Checksum: f316c576bbc3dcd006d2f9ba9178463cb8bc15a6 Type: SHA-1