d37089eca22ab3938ba04dadac760c8c pmc_32971903.pdf 48f037b295bc86cdeb5de26531c1973221b27ac9 pmc_32971903.pdf 710e979cede42b8ef547ab638b428c23f573d7d00f15b800b6b2b458eb40272e pmc_32971903.pdf Title: An Overview of Alternative Splicing Defects Implicated in Myotonic Dystrophy Type I Subject: Myotonic dystrophy type I (DM1) is the most common form of adult muscular dystrophy, caused by expansion of a CTG triplet repeat in the 3' untranslated region (3'UTR) of the myotonic dystrophy protein kinase (DMPK) gene. The pathological CTG repeats result in protein trapping by expanded transcripts, a decreased DMPK translation and the disruption of the chromatin structure, affecting neighboring genes expression. The muscleblind-like (MBNL) and CUG-BP and ETR-3-like factors (CELF) are two families of tissue-specific regulators of developmentally programmed alternative splicing that act as antagonist regulators of several pre-mRNA targets, including troponin 2 (TNNT2), insulin receptor (INSR), chloride channel 1 (CLCN1) and MBNL2. Sequestration of MBNL proteins and up-regulation of CELF1 are key to DM1 pathology, inducing a spliceopathy that leads to a developmental remodelling of the transcriptome due to an adult-to-foetal splicing switch, which results in the loss of cell function and viability. Moreover, recent studies indicate that additional pathogenic mechanisms may also contribute to disease pathology, including a misregulation of cellular mRNA translation, localization and stability. This review focuses on the cause and effects of MBNL and CELF1 deregulation in DM1, describing the molecular mechanisms underlying alternative splicing misregulation for a deeper understanding of DM1 complexity. To contribute to this analysis, we have prepared a comprehensive list of transcript alterations involved in DM1 pathogenesis, as well as other deregulated mRNA processing pathways implications. Keywords: myotonic dystrophy; spliceopathy; DMPK; MBNL; CELF1 Author: Andrea López-Martínez, Patricia Soblechero-Martín, Laura de-la-Puente-Ovejero, Gisela Nogales-Gadea and Virginia Arechavala-Gomeza Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Tue Sep 22 12:58:33 2020 CEST ModDate: Tue Sep 22 12:58:33 2020 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 27 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1909407 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SPWOYS+URWPalladioL-Ital Type 1 Custom yes yes no 101 0 UUFRRF+URWPalladioL-Bold Type 1 Custom yes yes no 102 0 YWWVQQ+VnURWPalladioL-Bold Type 1 Custom yes yes no 103 0 FLMFRD+URWPalladioL-Roma Type 1 Custom yes yes no 104 0 AWHDWW+VnURWPalladioL Type 1 Custom yes yes no 105 0 SVVJCD+Rpxr Type 1 Builtin yes yes no 106 0 MHORSP+Pxsy Type 1 Builtin yes yes no 107 0 HIZBRM+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 112 0 KONDUX+EuphemiaUCAS-Bold Type 1C WinAnsi yes yes no 113 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 132 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 133 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 134 0 MFIGJL+Rpxb Type 1 Builtin yes yes no 208 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 213 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 214 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 215 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 216 0 Times New Roman TrueType WinAnsi no no no 217 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 317 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 318 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 319 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 320 0 Times New Roman TrueType WinAnsi no no no 321 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 369 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 370 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 371 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 372 0 Times New Roman TrueType WinAnsi no no no 373 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 425 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 426 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 427 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 428 0 Times New Roman TrueType WinAnsi no no no 429 0 QDCWHF+EURM10 Type 1 Builtin yes yes no 473 0 DVTEVH+URWPalladioL-BoldItal Type 1 Custom yes yes no 497 0 BGEWMG+Rpxbi Type 1 Builtin yes yes no 670 0 GBLQZB+Rpxi Type 1 Builtin yes yes no 799 0 VSHNAE+Rpcxr Type 1 Builtin yes yes no 935 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-22 02:42:40 CEST RepresentationInformation: pmc_32971903.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-11-09 03:38:07 CET Size: 1909407 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮ㄮㄩ‾㸊⡜㌷㙜㌷㝜〰きべはぴはのどっぜ〴ぜ〰いべびぴひはばとべぜ〴ぜ〰ごべばづぜ〴ぜ〰ぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮ㄮ㈩‾㸊⡜㌷㙜㌷㝜〰ぁぬぴづひのちぴどぶづぜ〴ぜ〰こばぬどっどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Children: Item: Title: きべはぴはのどっぜ〴ぜ〰いべびぴひはばとべぜ〴ぜ〰ごべばづぜ〴ぜ〰ぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮ㄮ㈩‾㸊⡜㌷㙜㌷㝜〰ぁぬぴづひのちぴどぶづぜ〴ぜ〰こばぬどっどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: ぁぬぴづひのちぴどぶづぜ〴ぜ〰こばぬどっどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: きふびっぬづぢぬどのつ〭がどにづぜ〴ぜ〰ぜ〵ぜ〰きあぎがぜ〵ㅜ〰ぜ〴ぜ〰ぐひはぴづどのびぜ〴ぜ〰ちのつぜ〴ぜ〰きちのぴちどのどのでぜ〴ぜ〰きあぎが〯ぃぅがう〱ぜ〴ぜ〰ぅぱふどぬどぢひどふねぜ〴ぜ〰どのぜ〴ぜ〰いき〱ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰きあぎが〭いづばづのつづのぴぜ〴ぜ〰こばぬどっどのでぜ〴ぜ〰げづでふぬちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰きあぎがぜ〴ぜ〰ちのつぜ〴ぜ〰ぃぅがう〱ぜ〴ぜ〰ぉねばぬどっちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰いき〱ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: きあぎが〭いづばづのつづのぴぜ〴ぜ〰こばぬどっどのでぜ〴ぜ〰げづでふぬちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰きあぎがぜ〴ぜ〰ちのつぜ〴ぜ〰ぃぅがう〱ぜ〴ぜ〰ぉねばぬどっちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰いき〱ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: きあぎがぜ〴ぜ〰ちのつぜ〴ぜ〰ぃぅがう〱ぜ〴ぜ〰ぉねばぬどっちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰いき〱ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こばぬどっづはばちぴとべぜ〴ぜ〰いふづぜ〴ぜ〰ぴはぜ〴ぜ〰げぎぁぜ〴ぜ〰ごはへどっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰きどびひづでふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁぜ〴ぜ〰ぐひはっづびびどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸱ Children: Item: Title: きどびひづでふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁぜ〴ぜ〰ぐひはっづびびどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸱ Children: Item: Title: ごひちのびっひどばぴびぜ〴ぜ〰ぁぬぴづひづつぜ〴ぜ〰どのぜ〴ぜ〰いき〱ぜ〴ぜ〰あひちどのぜ〴ぜ〰ごどびびふづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸲ Item: Title: ごひちのびっひどばぴびぜ〴ぜ〰ぁぬぴづひづつぜ〴ぜ〰どのぜ〴ぜ〰いき〱ぜ〴ぜ〰こにづぬづぴちぬぜ〴ぜ〰きふびっぬづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸳ Item: Title: ごひちのびっひどばぴびぜ〴ぜ〰ぁぬぴづひづつぜ〴ぜ〰どのぜ〴ぜ〰いき〱ぜ〴ぜ〰ぃちひつどちっぜ〴ぜ〰きふびっぬづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰きどびひづでふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰こぴちぢどぬどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰きどびひづでふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁぜ〴ぜ〰ごひちのびぬちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: きどびひづでふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰こぴちぢどぬどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰きどびひづでふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁぜ〴ぜ〰ごひちのびぬちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: きどびひづでふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁぜ〴ぜ〰ごひちのびぬちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: SPWOYS+URWPalladioL-Ital FontSubset: true FirstChar: 44 LastChar: 122 FontDescriptor: FontName: SPWOYS+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: UUFRRF+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: UUFRRF+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: YWWVQQ+VnURWPalladioL-Bold FontSubset: true FirstChar: 189 LastChar: 226 FontDescriptor: FontName: YWWVQQ+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: VSHNAE+Rpcxr FontSubset: true FirstChar: 169 LastChar: 169 FontDescriptor: FontName: VSHNAE+Rpcxr Flags: Symbolic FontBBox: -212, -286, 1344, 973 FontFile: true Font: BaseFont: FLMFRD+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: FLMFRD+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: AWHDWW+VnURWPalladioL FontSubset: true FirstChar: 161 LastChar: 243 FontDescriptor: FontName: AWHDWW+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: SVVJCD+Rpxr FontSubset: true FirstChar: 11 LastChar: 61 FontDescriptor: FontName: SVVJCD+Rpxr Flags: Symbolic FontBBox: -40, -283, 904, 728 FontFile: true Font: BaseFont: MHORSP+Pxsy FontSubset: true FirstChar: 48 LastChar: 48 FontDescriptor: FontName: MHORSP+Pxsy Flags: Symbolic FontBBox: -21, -994, 1292, 912 FontFile: true Font: BaseFont: MFIGJL+Rpxb FontSubset: true FirstChar: 47 LastChar: 47 FontDescriptor: FontName: MFIGJL+Rpxb Flags: Symbolic FontBBox: -57, -266, 932, 729 FontFile: true Font: BaseFont: DVTEVH+URWPalladioL-BoldItal FontSubset: true FirstChar: 49 LastChar: 90 FontDescriptor: FontName: DVTEVH+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QDCWHF+EURM10 FontSubset: true FirstChar: 11 LastChar: 12 FontDescriptor: FontName: QDCWHF+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: BGEWMG+Rpxbi FontSubset: true FirstChar: 47 LastChar: 47 FontDescriptor: FontName: BGEWMG+Rpxbi Flags: Symbolic FontBBox: -130, -281, 1004, 729 FontFile: true Font: BaseFont: GBLQZB+Rpxi FontSubset: true FirstChar: 11 LastChar: 11 FontDescriptor: FontName: GBLQZB+Rpxi Flags: Symbolic FontBBox: -162, -280, 856, 733 FontFile: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 75, 757, 176, 793 Annotation: Subtype: Link Rect: 474, 757, 519, 793 Annotation: Subtype: Link Rect: 190, 660, 201, 674 Annotation: Subtype: Link Rect: 471, 660, 482, 674 Annotation: Subtype: Link Rect: 183, 647, 194, 660 Annotation: Subtype: Link Rect: 367, 647, 378, 660 Annotation: Subtype: Link Rect: 466, 532, 518, 551 Annotation: Subtype: Link Rect: 403, 156, 410, 165 ActionDest: 731 Annotation: Subtype: Link Rect: 411, 156, 418, 165 ActionDest: 731 Annotation: Subtype: Link Rect: 216, 115, 223, 124 ActionDest: 731 Annotation: Subtype: Link Rect: 223, 115, 230, 124 ActionDest: 731 Annotation: Subtype: Link Rect: 215, 102, 222, 111 ActionDest: 731 Annotation: Subtype: Link Rect: 162, 38, 244, 50 Annotation: Subtype: Link Rect: 410, 38, 519, 50 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 191, 696, 198, 705 ActionDest: 731 Annotation: Subtype: Link Rect: 109, 669, 116, 678 ActionDest: 731 Annotation: Subtype: Link Rect: 116, 669, 123, 678 ActionDest: 731 Annotation: Subtype: Link Rect: 442, 669, 449, 678 ActionDest: 731 Annotation: Subtype: Link Rect: 166, 655, 178, 665 ActionDest: 731 Annotation: Subtype: Link Rect: 259, 601, 271, 611 ActionDest: 731 Annotation: Subtype: Link Rect: 271, 601, 283, 611 ActionDest: 761 Annotation: Subtype: Link Rect: 488, 574, 500, 584 ActionDest: 731 Annotation: Subtype: Link Rect: 503, 574, 515, 584 ActionDest: 761 Annotation: Subtype: Link Rect: 114, 534, 126, 543 ActionDest: 761 Annotation: Subtype: Link Rect: 126, 534, 138, 543 ActionDest: 761 Annotation: Subtype: Link Rect: 227, 507, 239, 516 ActionDest: 761 Annotation: Subtype: Link Rect: 239, 507, 251, 516 ActionDest: 761 Annotation: Subtype: Link Rect: 341, 412, 353, 421 ActionDest: 761 Annotation: Subtype: Link Rect: 344, 385, 356, 394 ActionDest: 761 Annotation: Subtype: Link Rect: 448, 315, 460, 325 ActionDest: 761 Annotation: Subtype: Link Rect: 491, 262, 503, 271 ActionDest: 761 Annotation: Subtype: Link Rect: 503, 262, 515, 271 ActionDest: 761 Annotation: Subtype: Link Rect: 363, 194, 375, 203 ActionDest: 761 Annotation: Subtype: Link Rect: 378, 194, 390, 203 ActionDest: 761 Annotation: Subtype: Link Rect: 155, 153, 167, 163 ActionDest: 761 Annotation: Subtype: Link Rect: 168, 153, 180, 163 ActionDest: 761 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 491, 729, 503, 738 ActionDest: 761 Annotation: Subtype: Link Rect: 503, 729, 515, 738 ActionDest: 761 Annotation: Subtype: Link Rect: 378, 688, 390, 698 ActionDest: 761 Annotation: Subtype: Link Rect: 391, 688, 403, 698 ActionDest: 761 Annotation: Subtype: Link Rect: 353, 661, 365, 671 ActionDest: 796 Annotation: Subtype: Link Rect: 366, 661, 378, 671 ActionDest: 796 Annotation: Subtype: Link Rect: 269, 514, 281, 524 ActionDest: 796 Annotation: Subtype: Link Rect: 282, 514, 294, 524 ActionDest: 796 Annotation: Subtype: Link Rect: 503, 501, 515, 510 ActionDest: 796 Annotation: Subtype: Link Rect: 416, 460, 428, 470 ActionDest: 796 Annotation: Subtype: Link Rect: 431, 460, 443, 470 ActionDest: 796 Annotation: Subtype: Link Rect: 378, 444, 385, 456 ActionDest: 205 Annotation: Subtype: Link Rect: 335, 379, 347, 388 ActionDest: 796 Annotation: Subtype: Link Rect: 347, 379, 359, 388 ActionDest: 796 Annotation: Subtype: Link Rect: 488, 352, 500, 361 ActionDest: 796 Annotation: Subtype: Link Rect: 503, 352, 515, 361 ActionDest: 796 Annotation: Subtype: Link Rect: 367, 95, 374, 107 ActionDest: 205 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 225, 702, 237, 711 ActionDest: 796 Annotation: Subtype: Link Rect: 237, 702, 249, 711 ActionDest: 796 Annotation: Subtype: Link Rect: 250, 702, 261, 711 ActionDest: 796 Annotation: Subtype: Link Rect: 136, 675, 148, 684 ActionDest: 796 Annotation: Subtype: Link Rect: 113, 661, 125, 671 ActionDest: 796 Annotation: Subtype: Link Rect: 126, 661, 138, 671 ActionDest: 796 Annotation: Subtype: Link Rect: 180, 621, 192, 630 ActionDest: 796 Annotation: Subtype: Link Rect: 491, 567, 503, 576 ActionDest: 796 Annotation: Subtype: Link Rect: 503, 567, 515, 576 ActionDest: 796 Annotation: Subtype: Link Rect: 412, 540, 424, 549 ActionDest: 796 Annotation: Subtype: Link Rect: 425, 540, 437, 549 ActionDest: 796 Annotation: Subtype: Link Rect: 437, 540, 449, 549 ActionDest: 832 Annotation: Subtype: Link Rect: 415, 432, 427, 441 ActionDest: 796 Annotation: Subtype: Link Rect: 428, 432, 440, 441 ActionDest: 832 Annotation: Subtype: Link Rect: 443, 432, 455, 441 ActionDest: 832 Annotation: Subtype: Link Rect: 192, 378, 204, 387 ActionDest: 832 Annotation: Subtype: Link Rect: 205, 378, 217, 387 ActionDest: 832 Annotation: Subtype: Link Rect: 318, 334, 325, 346 ActionDest: 311 Annotation: Subtype: Link Rect: 451, 310, 463, 319 ActionDest: 832 Annotation: Subtype: Link Rect: 478, 297, 490, 306 ActionDest: 832 Annotation: Subtype: Link Rect: 208, 280, 215, 292 ActionDest: 311 Annotation: Subtype: Link Rect: 174, 215, 186, 225 ActionDest: 832 Annotation: Subtype: Link Rect: 187, 215, 199, 225 ActionDest: 832 Annotation: Subtype: Link Rect: 199, 215, 211, 225 ActionDest: 832 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 163, 253, 175, 262 ActionDest: 832 Annotation: Subtype: Link Rect: 176, 253, 188, 262 ActionDest: 832 Annotation: Subtype: Link Rect: 428, 223, 435, 235 ActionDest: 362 Annotation: Subtype: Link Rect: 260, 212, 272, 222 ActionDest: 796 Annotation: Subtype: Link Rect: 272, 212, 284, 222 ActionDest: 832 Annotation: Subtype: Link Rect: 180, 185, 192, 195 ActionDest: 832 Annotation: Subtype: Link Rect: 193, 185, 205, 195 ActionDest: 832 Annotation: Subtype: Link Rect: 361, 131, 373, 141 ActionDest: 832 Annotation: Subtype: Link Rect: 228, 91, 240, 100 ActionDest: 832 Annotation: Subtype: Link Rect: 240, 91, 252, 100 ActionDest: 832 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 304, 742, 316, 752 ActionDest: 832 Annotation: Subtype: Link Rect: 316, 742, 328, 752 ActionDest: 832 Annotation: Subtype: Link Rect: 97, 675, 109, 684 ActionDest: 796 Annotation: Subtype: Link Rect: 109, 675, 121, 684 ActionDest: 832 Annotation: Subtype: Link Rect: 302, 648, 314, 657 ActionDest: 832 Annotation: Subtype: Link Rect: 305, 634, 317, 644 ActionDest: 796 Annotation: Subtype: Link Rect: 440, 621, 451, 630 ActionDest: 761 Annotation: Subtype: Link Rect: 452, 621, 464, 630 ActionDest: 832 Annotation: Subtype: Link Rect: 412, 176, 419, 188 ActionDest: 362 Annotation: Subtype: Link Rect: 425, 179, 437, 188 ActionDest: 832 Annotation: Subtype: Link Rect: 438, 179, 450, 188 ActionDest: 832 Annotation: Subtype: Link Rect: 212, 138, 224, 148 ActionDest: 832 Annotation: Subtype: Link Rect: 227, 138, 239, 148 ActionDest: 864 Annotation: Subtype: Link Rect: 456, 111, 467, 121 ActionDest: 832 Annotation: Subtype: Link Rect: 468, 111, 480, 121 ActionDest: 864 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 159, 742, 171, 752 ActionDest: 832 Annotation: Subtype: Link Rect: 172, 743, 184, 752 ActionDest: 864 Annotation: Subtype: Link Rect: 168, 713, 175, 725 ActionDest: 362 Annotation: Subtype: Link Rect: 261, 715, 273, 725 ActionDest: 832 Annotation: Subtype: Link Rect: 276, 715, 288, 725 ActionDest: 832 Annotation: Subtype: Link Rect: 362, 632, 374, 641 ActionDest: 832 Annotation: Subtype: Link Rect: 375, 632, 387, 641 ActionDest: 864 Annotation: Subtype: Link Rect: 511, 629, 518, 641 ActionDest: 416 Annotation: Subtype: Link Rect: 293, 605, 305, 614 ActionDest: 864 Annotation: Subtype: Link Rect: 278, 548, 285, 560 ActionDest: 416 Annotation: Subtype: Link Rect: 321, 548, 329, 560 ActionDest: 416 Annotation: Subtype: Link Rect: 336, 146, 348, 155 ActionDest: 864 Annotation: Subtype: Link Rect: 186, 105, 198, 114 ActionDest: 761 Annotation: Subtype: Link Rect: 198, 105, 210, 114 ActionDest: 864 Annotation: Subtype: Link Rect: 457, 78, 469, 87 ActionDest: 864 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 362, 729, 374, 738 ActionDest: 796 Annotation: Subtype: Link Rect: 374, 729, 386, 738 ActionDest: 864 Annotation: Subtype: Link Rect: 387, 729, 399, 738 ActionDest: 864 Annotation: Subtype: Link Rect: 395, 688, 407, 698 ActionDest: 864 Annotation: Subtype: Link Rect: 408, 688, 419, 698 ActionDest: 864 Annotation: Subtype: Link Rect: 145, 616, 152, 628 ActionDest: 416 Annotation: Subtype: Link Rect: 312, 619, 324, 628 ActionDest: 832 Annotation: Subtype: Link Rect: 324, 619, 336, 628 ActionDest: 864 Annotation: Subtype: Link Rect: 127, 565, 139, 574 ActionDest: 864 Annotation: Subtype: Link Rect: 149, 538, 161, 547 ActionDest: 832 Annotation: Subtype: Link Rect: 118, 454, 130, 464 ActionDest: 796 Annotation: Subtype: Link Rect: 149, 441, 156, 450 ActionDest: 494 Annotation: Subtype: Link Rect: 316, 414, 328, 423 ActionDest: 864 Annotation: Subtype: Link Rect: 332, 373, 344, 383 ActionDest: 864 Annotation: Subtype: Link Rect: 344, 373, 356, 383 ActionDest: 864 Annotation: Subtype: Link Rect: 332, 306, 344, 315 ActionDest: 864 Annotation: Subtype: Link Rect: 244, 252, 256, 261 ActionDest: 864 Annotation: Subtype: Link Rect: 257, 252, 269, 261 ActionDest: 864 Annotation: Subtype: Link Rect: 211, 198, 223, 207 ActionDest: 761 Annotation: Subtype: Link Rect: 223, 198, 235, 207 ActionDest: 864 Annotation: Subtype: Link Rect: 236, 198, 248, 207 ActionDest: 864 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 368, 406, 380, 414 ActionDest: 864 Annotation: Subtype: Link Rect: 377, 374, 388, 383 ActionDest: 864 Annotation: Subtype: Link Rect: 378, 335, 390, 343 ActionDest: 864 Annotation: Subtype: Link Rect: 378, 312, 390, 320 ActionDest: 761 Annotation: Subtype: Link Rect: 379, 296, 390, 305 ActionDest: 864 Annotation: Subtype: Link Rect: 368, 281, 380, 289 ActionDest: 864 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 220, 666, 227, 678 ActionDest: 629 Annotation: Subtype: Link Rect: 354, 655, 366, 665 ActionDest: 761 Annotation: Subtype: Link Rect: 366, 655, 378, 665 ActionDest: 832 Annotation: Subtype: Link Rect: 379, 655, 391, 665 ActionDest: 864 Annotation: Subtype: Link Rect: 147, 601, 159, 611 ActionDest: 864 Annotation: Subtype: Link Rect: 275, 601, 287, 611 ActionDest: 864 Annotation: Subtype: Link Rect: 474, 534, 486, 543 ActionDest: 864 Annotation: Subtype: Link Rect: 412, 507, 424, 516 ActionDest: 864 Annotation: Subtype: Link Rect: 324, 493, 336, 502 ActionDest: 890 Annotation: Subtype: Link Rect: 415, 466, 427, 475 ActionDest: 761 Annotation: Subtype: Link Rect: 422, 412, 434, 421 ActionDest: 864 Annotation: Subtype: Link Rect: 435, 412, 447, 421 ActionDest: 890 Annotation: Subtype: Link Rect: 204, 277, 216, 286 ActionDest: 864 Annotation: Subtype: Link Rect: 288, 142, 300, 151 ActionDest: 890 Annotation: Subtype: Link Rect: 303, 142, 315, 151 ActionDest: 890 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 149, 702, 161, 711 ActionDest: 761 Annotation: Subtype: Link Rect: 161, 702, 173, 711 ActionDest: 890 Annotation: Subtype: Link Rect: 374, 675, 386, 684 ActionDest: 890 Annotation: Subtype: Link Rect: 352, 621, 364, 630 ActionDest: 890 Annotation: Subtype: Link Rect: 299, 607, 311, 617 ActionDest: 761 Annotation: Subtype: Link Rect: 157, 580, 169, 590 ActionDest: 890 Annotation: Subtype: Link Rect: 150, 513, 162, 522 ActionDest: 761 Annotation: Subtype: Link Rect: 163, 513, 175, 522 ActionDest: 890 Annotation: Subtype: Link Rect: 114, 405, 126, 414 ActionDest: 761 Annotation: Subtype: Link Rect: 127, 405, 139, 414 ActionDest: 890 Annotation: Subtype: Link Rect: 387, 351, 399, 360 ActionDest: 832 Annotation: Subtype: Link Rect: 400, 351, 412, 360 ActionDest: 890 Annotation: Subtype: Link Rect: 218, 256, 230, 265 ActionDest: 864 Annotation: Subtype: Link Rect: 231, 256, 248, 265 ActionDest: 890 Annotation: Subtype: Link Rect: 153, 134, 165, 144 ActionDest: 832 Annotation: Subtype: Link Rect: 166, 134, 177, 144 ActionDest: 864 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 460, 729, 477, 738 ActionDest: 890 Annotation: Subtype: Link Rect: 251, 594, 263, 603 ActionDest: 864 Annotation: Subtype: Link Rect: 263, 594, 280, 603 ActionDest: 890 Annotation: Subtype: Link Rect: 366, 526, 378, 535 ActionDest: 832 Annotation: Subtype: Link Rect: 379, 526, 391, 535 ActionDest: 864 Annotation: Subtype: Link Rect: 407, 391, 419, 400 ActionDest: 761 Annotation: Subtype: Link Rect: 419, 391, 436, 400 ActionDest: 890 Annotation: Subtype: Link Rect: 433, 283, 445, 292 ActionDest: 864 Annotation: Subtype: Link Rect: 446, 283, 463, 292 ActionDest: 890 Annotation: Subtype: Link Rect: 264, 229, 276, 238 ActionDest: 796 Annotation: Subtype: Link Rect: 292, 175, 304, 184 ActionDest: 796 Annotation: Subtype: Link Rect: 442, 121, 454, 130 ActionDest: 761 Annotation: Subtype: Link Rect: 454, 121, 466, 130 ActionDest: 864 Annotation: Subtype: Link Rect: 467, 121, 484, 130 ActionDest: 890 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 228, 729, 240, 738 ActionDest: 864 Annotation: Subtype: Link Rect: 394, 675, 406, 684 ActionDest: 864 Annotation: Subtype: Link Rect: 268, 526, 280, 535 ActionDest: 761 Annotation: Subtype: Link Rect: 281, 526, 293, 535 ActionDest: 864 Annotation: Subtype: Link Rect: 210, 472, 222, 481 ActionDest: 864 Annotation: Subtype: Link Rect: 370, 391, 382, 400 ActionDest: 761 Annotation: Subtype: Link Rect: 323, 337, 335, 346 ActionDest: 761 Annotation: Subtype: Link Rect: 414, 297, 426, 306 ActionDest: 864 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 375, 417, 386, 425 ActionDest: 761 Annotation: Subtype: Link Rect: 371, 393, 382, 401 ActionDest: 890 Annotation: Subtype: Link Rect: 375, 369, 386, 377 ActionDest: 864 Annotation: Subtype: Link Rect: 369, 345, 379, 353 ActionDest: 890 Annotation: Subtype: Link Rect: 366, 321, 377, 329 ActionDest: 890 Annotation: Subtype: Link Rect: 375, 297, 386, 305 ActionDest: 864 Annotation: Subtype: Link Rect: 370, 278, 381, 286 ActionDest: 890 Annotation: Subtype: Link Rect: 373, 268, 384, 276 ActionDest: 890 Annotation: Subtype: Link Rect: 366, 254, 381, 262 ActionDest: 890 Annotation: Subtype: Link Rect: 375, 244, 386, 252 ActionDest: 761 Annotation: Subtype: Link Rect: 375, 230, 386, 238 ActionDest: 864 Annotation: Subtype: Link Rect: 362, 216, 377, 223 ActionDest: 890 Annotation: Subtype: Link Rect: 375, 189, 386, 196 ActionDest: 761 Annotation: Subtype: Link Rect: 375, 160, 386, 168 ActionDest: 864 Annotation: Subtype: Link Rect: 375, 136, 386, 144 ActionDest: 761 Annotation: Subtype: Link Rect: 368, 102, 383, 110 ActionDest: 890 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 376, 448, 387, 456 ActionDest: 832 Annotation: Subtype: Link Rect: 375, 434, 386, 441 ActionDest: 761 Annotation: Subtype: Link Rect: 375, 419, 386, 427 ActionDest: 864 Annotation: Subtype: Link Rect: 367, 400, 382, 408 ActionDest: 890 Annotation: Subtype: Link Rect: 371, 381, 386, 389 ActionDest: 890 Annotation: Subtype: Link Rect: 375, 366, 386, 374 ActionDest: 864 Annotation: Subtype: Link Rect: 371, 352, 386, 360 ActionDest: 890 Annotation: Subtype: Link Rect: 375, 333, 386, 341 ActionDest: 864 Annotation: Subtype: Link Rect: 375, 309, 386, 316 ActionDest: 864 Annotation: Subtype: Link Rect: 375, 285, 386, 292 ActionDest: 864 Annotation: Subtype: Link Rect: 375, 260, 386, 268 ActionDest: 864 Annotation: Subtype: Link Rect: 363, 236, 374, 244 ActionDest: 832 Annotation: Subtype: Link Rect: 364, 205, 375, 213 ActionDest: 864 Annotation: Subtype: Link Rect: 371, 176, 382, 184 ActionDest: 890 Annotation: Subtype: Link Rect: 362, 152, 373, 160 ActionDest: 796 Annotation: Subtype: Link Rect: 375, 128, 386, 136 ActionDest: 864 Annotation: Subtype: Link Rect: 375, 104, 386, 112 ActionDest: 864 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 389, 709, 406, 719 ActionDest: 920 Annotation: Subtype: Link Rect: 407, 709, 424, 719 ActionDest: 920 Annotation: Subtype: Link Rect: 214, 655, 231, 665 ActionDest: 920 Annotation: Subtype: Link Rect: 267, 642, 274, 651 ActionDest: 667 Annotation: Subtype: Link Rect: 411, 547, 428, 557 ActionDest: 920 Annotation: Subtype: Link Rect: 486, 453, 498, 462 ActionDest: 890 Annotation: Subtype: Link Rect: 498, 453, 515, 462 ActionDest: 920 Annotation: Subtype: Link Rect: 348, 331, 360, 340 ActionDest: 832 Annotation: Subtype: Link Rect: 360, 331, 377, 340 ActionDest: 920 Annotation: Subtype: Link Rect: 397, 250, 409, 259 ActionDest: 761 Annotation: Subtype: Link Rect: 410, 250, 427, 259 ActionDest: 920 Annotation: Subtype: Link Rect: 342, 155, 354, 165 ActionDest: 832 Annotation: Subtype: Link Rect: 355, 155, 367, 165 ActionDest: 864 Annotation: Subtype: Link Rect: 367, 155, 384, 165 ActionDest: 920 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 412, 414, 424, 422 ActionDest: 890 Annotation: Subtype: Link Rect: 407, 403, 423, 411 ActionDest: 920 Annotation: Subtype: Link Rect: 406, 377, 422, 385 ActionDest: 920 Annotation: Subtype: Link Rect: 381, 340, 397, 348 ActionDest: 920 Annotation: Subtype: Link Rect: 403, 303, 415, 311 ActionDest: 832 Annotation: Subtype: Link Rect: 407, 292, 423, 300 ActionDest: 920 Annotation: Subtype: Link Rect: 404, 255, 415, 263 ActionDest: 832 Annotation: Subtype: Link Rect: 396, 234, 408, 242 ActionDest: 864 Annotation: Subtype: Link Rect: 417, 200, 429, 208 ActionDest: 761 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 192, 648, 209, 657 ActionDest: 920 Annotation: Subtype: Link Rect: 319, 578, 331, 587 ActionDest: 796 Annotation: Subtype: Link Rect: 226, 483, 238, 493 ActionDest: 796 Annotation: Subtype: Link Rect: 404, 456, 416, 466 ActionDest: 796 Annotation: Subtype: Link Rect: 417, 457, 433, 466 ActionDest: 920 Annotation: Subtype: Link Rect: 441, 443, 458, 452 ActionDest: 920 Annotation: Subtype: Link Rect: 472, 416, 489, 425 ActionDest: 920 Annotation: Subtype: Link Rect: 402, 362, 419, 371 ActionDest: 920 Annotation: Subtype: Link Rect: 394, 281, 405, 290 ActionDest: 796 Annotation: Subtype: Link Rect: 406, 281, 423, 290 ActionDest: 920 Annotation: Subtype: Link Rect: 423, 281, 440, 290 ActionDest: 920 Annotation: Subtype: Link Rect: 393, 146, 410, 155 ActionDest: 920 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 423, 715, 435, 725 ActionDest: 832 Annotation: Subtype: Link Rect: 436, 715, 453, 725 ActionDest: 920 Annotation: Subtype: Link Rect: 490, 675, 502, 684 ActionDest: 832 Annotation: Subtype: Link Rect: 503, 675, 515, 684 ActionDest: 832 Annotation: Subtype: Link Rect: 113, 580, 130, 590 ActionDest: 920 Annotation: Subtype: Link Rect: 175, 540, 192, 549 ActionDest: 920 Annotation: Subtype: Link Rect: 192, 540, 209, 549 ActionDest: 920 Annotation: Subtype: Link Rect: 443, 513, 460, 522 ActionDest: 920 Annotation: Subtype: Link Rect: 158, 405, 175, 414 ActionDest: 920 Annotation: Subtype: Link Rect: 176, 405, 192, 414 ActionDest: 932 Page: Sequence: 20 Annotations: Annotation: Subtype: Link Rect: 118, 661, 135, 671 ActionDest: 932 Annotation: Subtype: Link Rect: 216, 401, 253, 412 Annotation: Subtype: Link Rect: 260, 401, 296, 412 Annotation: Subtype: Link Rect: 473, 375, 511, 386 Annotation: Subtype: Link Rect: 480, 363, 516, 374 Annotation: Subtype: Link Rect: 480, 350, 516, 361 Annotation: Subtype: Link Rect: 100, 338, 136, 348 Annotation: Subtype: Link Rect: 100, 299, 137, 309 Annotation: Subtype: Link Rect: 476, 233, 514, 245 Annotation: Subtype: Link Rect: 291, 195, 329, 206 Annotation: Subtype: Link Rect: 335, 195, 371, 206 Annotation: Subtype: Link Rect: 100, 157, 137, 167 Annotation: Subtype: Link Rect: 334, 79, 372, 89 Page: Sequence: 21 Annotations: Annotation: Subtype: Link Rect: 321, 714, 359, 725 Annotation: Subtype: Link Rect: 365, 714, 401, 725 Annotation: Subtype: Link Rect: 258, 663, 295, 673 Annotation: Subtype: Link Rect: 302, 663, 338, 673 Annotation: Subtype: Link Rect: 224, 624, 262, 635 Annotation: Subtype: Link Rect: 268, 624, 304, 635 Annotation: Subtype: Link Rect: 440, 585, 478, 596 Annotation: Subtype: Link Rect: 421, 533, 459, 544 Annotation: Subtype: Link Rect: 194, 496, 231, 506 Annotation: Subtype: Link Rect: 100, 457, 137, 467 Annotation: Subtype: Link Rect: 214, 430, 519, 441 Annotation: Subtype: Link Rect: 97, 417, 180, 428 Annotation: Subtype: Link Rect: 177, 392, 214, 402 Annotation: Subtype: Link Rect: 123, 341, 160, 351 Annotation: Subtype: Link Rect: 172, 315, 210, 325 Annotation: Subtype: Link Rect: 406, 288, 444, 299 Annotation: Subtype: Link Rect: 172, 263, 210, 273 Annotation: Subtype: Link Rect: 216, 263, 252, 273 Annotation: Subtype: Link Rect: 439, 236, 475, 247 Annotation: Subtype: Link Rect: 481, 236, 516, 247 Annotation: Subtype: Link Rect: 181, 199, 219, 209 Annotation: Subtype: Link Rect: 225, 199, 261, 209 Annotation: Subtype: Link Rect: 288, 172, 326, 183 Annotation: Subtype: Link Rect: 172, 134, 210, 144 Annotation: Subtype: Link Rect: 271, 94, 308, 105 Page: Sequence: 22 Annotations: Annotation: Subtype: Link Rect: 192, 715, 230, 725 Annotation: Subtype: Link Rect: 236, 715, 272, 725 Annotation: Subtype: Link Rect: 267, 675, 304, 686 Annotation: Subtype: Link Rect: 283, 638, 320, 648 Annotation: Subtype: Link Rect: 327, 638, 363, 648 Annotation: Subtype: Link Rect: 424, 611, 461, 622 Annotation: Subtype: Link Rect: 467, 611, 503, 622 Annotation: Subtype: Link Rect: 479, 585, 516, 596 Annotation: Subtype: Link Rect: 100, 573, 136, 583 Annotation: Subtype: Link Rect: 145, 534, 182, 544 Annotation: Subtype: Link Rect: 383, 508, 420, 519 Annotation: Subtype: Link Rect: 452, 482, 489, 493 Annotation: Subtype: Link Rect: 426, 456, 463, 467 Annotation: Subtype: Link Rect: 469, 456, 506, 467 Annotation: Subtype: Link Rect: 466, 430, 504, 441 Annotation: Subtype: Link Rect: 154, 379, 191, 389 Annotation: Subtype: Link Rect: 100, 341, 137, 351 Annotation: Subtype: Link Rect: 429, 314, 466, 325 Annotation: Subtype: Link Rect: 472, 314, 508, 325 Annotation: Subtype: Link Rect: 287, 275, 325, 286 Annotation: Subtype: Link Rect: 331, 275, 367, 286 Annotation: Subtype: Link Rect: 423, 249, 460, 260 Annotation: Subtype: Link Rect: 466, 249, 502, 260 Annotation: Subtype: Link Rect: 367, 224, 405, 234 Annotation: Subtype: Link Rect: 411, 224, 447, 234 Annotation: Subtype: Link Rect: 181, 186, 219, 196 Annotation: Subtype: Link Rect: 100, 147, 137, 157 Annotation: Subtype: Link Rect: 448, 120, 485, 131 Annotation: Subtype: Link Rect: 355, 82, 393, 92 Page: Sequence: 23 Annotations: Annotation: Subtype: Link Rect: 100, 715, 137, 725 Annotation: Subtype: Link Rect: 181, 676, 219, 686 Annotation: Subtype: Link Rect: 195, 638, 232, 648 Annotation: Subtype: Link Rect: 238, 638, 274, 648 Annotation: Subtype: Link Rect: 299, 611, 336, 622 Annotation: Subtype: Link Rect: 342, 611, 378, 622 Annotation: Subtype: Link Rect: 341, 585, 378, 596 Annotation: Subtype: Link Rect: 100, 547, 137, 557 Annotation: Subtype: Link Rect: 143, 547, 179, 557 Annotation: Subtype: Link Rect: 458, 521, 496, 531 Annotation: Subtype: Link Rect: 217, 482, 254, 493 Annotation: Subtype: Link Rect: 136, 457, 174, 467 Annotation: Subtype: Link Rect: 100, 418, 137, 428 Annotation: Subtype: Link Rect: 181, 379, 219, 389 Annotation: Subtype: Link Rect: 377, 353, 415, 364 Annotation: Subtype: Link Rect: 154, 315, 191, 325 Annotation: Subtype: Link Rect: 198, 315, 234, 325 Annotation: Subtype: Link Rect: 340, 288, 377, 299 Annotation: Subtype: Link Rect: 383, 288, 419, 299 Annotation: Subtype: Link Rect: 479, 262, 516, 273 Annotation: Subtype: Link Rect: 100, 250, 136, 260 Annotation: Subtype: Link Rect: 260, 224, 297, 234 Annotation: Subtype: Link Rect: 304, 224, 340, 234 Annotation: Subtype: Link Rect: 177, 186, 214, 196 Annotation: Subtype: Link Rect: 220, 186, 256, 196 Annotation: Subtype: Link Rect: 407, 159, 445, 170 Annotation: Subtype: Link Rect: 395, 133, 432, 144 Annotation: Subtype: Link Rect: 100, 82, 137, 92 Page: Sequence: 24 Annotations: Annotation: Subtype: Link Rect: 448, 727, 485, 738 Annotation: Subtype: Link Rect: 233, 702, 270, 712 Annotation: Subtype: Link Rect: 382, 663, 419, 673 Annotation: Subtype: Link Rect: 425, 663, 461, 673 Annotation: Subtype: Link Rect: 480, 637, 516, 648 Annotation: Subtype: Link Rect: 100, 625, 136, 635 Annotation: Subtype: Link Rect: 354, 585, 392, 596 Annotation: Subtype: Link Rect: 398, 585, 434, 596 Annotation: Subtype: Link Rect: 231, 559, 268, 570 Annotation: Subtype: Link Rect: 275, 559, 311, 570 Annotation: Subtype: Link Rect: 238, 521, 275, 531 Annotation: Subtype: Link Rect: 291, 495, 328, 506 Annotation: Subtype: Link Rect: 136, 444, 174, 454 Annotation: Subtype: Link Rect: 255, 417, 293, 428 Annotation: Subtype: Link Rect: 275, 391, 313, 402 Annotation: Subtype: Link Rect: 329, 366, 366, 376 Annotation: Subtype: Link Rect: 271, 327, 308, 338 Annotation: Subtype: Link Rect: 314, 327, 350, 338 Annotation: Subtype: Link Rect: 300, 250, 338, 260 Annotation: Subtype: Link Rect: 344, 250, 380, 260 Annotation: Subtype: Link Rect: 478, 211, 516, 222 Annotation: Subtype: Link Rect: 100, 199, 136, 209 Annotation: Subtype: Link Rect: 177, 147, 214, 157 Annotation: Subtype: Link Rect: 325, 120, 363, 131 Annotation: Subtype: Link Rect: 369, 120, 405, 131 Annotation: Subtype: Link Rect: 443, 94, 481, 105 Annotation: Subtype: Link Rect: 166, 69, 329, 80 Page: Sequence: 25 Annotations: Annotation: Subtype: Link Rect: 249, 715, 286, 725 Annotation: Subtype: Link Rect: 305, 676, 343, 686 Annotation: Subtype: Link Rect: 127, 638, 165, 648 Annotation: Subtype: Link Rect: 460, 598, 498, 609 Annotation: Subtype: Link Rect: 100, 560, 137, 570 Annotation: Subtype: Link Rect: 441, 521, 478, 531 Annotation: Subtype: Link Rect: 397, 482, 434, 493 Annotation: Subtype: Link Rect: 440, 482, 476, 493 Annotation: Subtype: Link Rect: 181, 431, 219, 441 Annotation: Subtype: Link Rect: 100, 392, 137, 402 Annotation: Subtype: Link Rect: 231, 353, 268, 364 Annotation: Subtype: Link Rect: 274, 353, 311, 364 Annotation: Subtype: Link Rect: 478, 327, 516, 338 Annotation: Subtype: Link Rect: 100, 315, 136, 325 Annotation: Subtype: Link Rect: 193, 276, 231, 286 Annotation: Subtype: Link Rect: 439, 249, 476, 260 Annotation: Subtype: Link Rect: 275, 224, 313, 234 Annotation: Subtype: Link Rect: 346, 185, 383, 196 Annotation: Subtype: Link Rect: 390, 185, 426, 196 Annotation: Subtype: Link Rect: 410, 159, 448, 170 Annotation: Subtype: Link Rect: 361, 120, 398, 131 Annotation: Subtype: Link Rect: 405, 120, 441, 131 Page: Sequence: 26 Annotations: Annotation: Subtype: Link Rect: 216, 714, 254, 725 Annotation: Subtype: Link Rect: 260, 714, 296, 725 Annotation: Subtype: Link Rect: 175, 676, 213, 686 Annotation: Subtype: Link Rect: 359, 637, 397, 648 Annotation: Subtype: Link Rect: 403, 637, 439, 648 Annotation: Subtype: Link Rect: 154, 599, 192, 609 Annotation: Subtype: Link Rect: 330, 559, 368, 570 Annotation: Subtype: Link Rect: 348, 521, 386, 531 Annotation: Subtype: Link Rect: 136, 483, 174, 493 Annotation: Subtype: Link Rect: 100, 444, 137, 454 Annotation: Subtype: Link Rect: 143, 444, 179, 454 Annotation: Subtype: Link Rect: 215, 418, 252, 428 Annotation: Subtype: Link Rect: 270, 378, 308, 389 Annotation: Subtype: Link Rect: 314, 378, 350, 389 Annotation: Subtype: Link Rect: 212, 340, 249, 351 Annotation: Subtype: Link Rect: 256, 340, 292, 351 Annotation: Subtype: Link Rect: 145, 302, 182, 312 Annotation: Subtype: Link Rect: 315, 275, 353, 286 Annotation: Subtype: Link Rect: 359, 275, 395, 286 Annotation: Subtype: Link Rect: 317, 250, 355, 260 Annotation: Subtype: Link Rect: 136, 212, 174, 222 Annotation: Subtype: Link Rect: 293, 185, 330, 196 Annotation: Subtype: Link Rect: 480, 159, 516, 170 Annotation: Subtype: Link Rect: 281, 121, 319, 131 Annotation: Subtype: Link Rect: 325, 121, 361, 131 Page: Sequence: 27 Annotations: Annotation: Subtype: Link Rect: 244, 728, 282, 738 Annotation: Subtype: Link Rect: 288, 728, 324, 738 Annotation: Subtype: Link Rect: 478, 701, 516, 712 Annotation: Subtype: Link Rect: 100, 689, 136, 699 Annotation: Subtype: Link Rect: 76, 647, 166, 678 Annotation: Subtype: Link Rect: 234, 642, 407, 652 Checksum: 478d9768 Type: CRC32 Checksum: d37089eca22ab3938ba04dadac760c8c Type: MD5 Checksum: 48f037b295bc86cdeb5de26531c1973221b27ac9 Type: SHA-1