4327c7e9b5482a93bb2618939a2e44f1 pmc_35215499.pdf 821545654fe8f3ef6bd666e7fb60ded20d9d2405 pmc_35215499.pdf 911cbf778cb447ace5ead578e2f78da16b96f6ea9d0cbf6ae67127e6b99b9425 pmc_35215499.pdf Title: Lipid Metabolism and Epigenetics Crosstalk in Prostate Cancer Subject: Prostate cancer (PCa) is the most commonly diagnosed malignant neoplasm in men in the Western world. Localized low-risk PCa has an excellent prognosis thanks to effective local treatments; however, despite the incorporation of new therapeutic strategies, metastatic PCa remains incurable mainly due to disease heterogeneity and the development of resistance to therapy. The mechanisms underlying PCa progression and therapy resistance are multiple and include metabolic reprogramming, especially in relation to lipid metabolism, as well as epigenetic remodelling, both of which enable cancer cells to adapt to dynamic changes in the tumour. Interestingly, metabolism and epigenetics are interconnected. Metabolism can regulate epigenetics through the direct influence of metabolites on epigenetic processes, while epigenetics can control metabolism by directly or indirectly regulating the expression of metabolic genes. Moreover, epidemiological studies suggest an association between a high-fat diet, which can alter the availability of metabolites, and PCa progression. Here, we review the alterations of lipid metabolism and epigenetics in PCa, before focusing on the mechanisms that connect them. We also discuss the influence of diet in this scenario. This information may help to identify prognostic and predictive biomarkers as well as targetable vulnerabilities. Keywords: prostate cancer; lipid metabolism; epigenetics; diet; fatty acid; cholesterol; DNA methylation; histone modifications; predictive biomarkers; therapeutic vulnerabilities Author: Juan C. Pardo, Vicenç Ruiz de Porras, Joan Gil, Albert Font, Manel Puig-Domingo and Mireia Jordà Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Feb 18 06:55:33 2022 CET ModDate: Fri Feb 18 07:01:25 2022 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 29 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1418256 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BCDWAK+VnURWPalladioL Type 1 Custom yes yes no 10 0 HKKCDU+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 WOLOAL+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 RIVHWD+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 GYREAE+CMSY10 Type 1 Builtin yes yes no 28 0 WNWTFR+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 40 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 44 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 48 0 HGMNRX+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 60 0 GOCQIR+EURM10 Type 1 Builtin yes yes no 82 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 97 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 101 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 105 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 119 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 123 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 127 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-05-07 04:29:30 CEST RepresentationInformation: pmc_35215499.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2022-03-06 18:36:52 CET Size: 1418256 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 896 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Lipid Metabolism Alterations: A Hallmark of PCa Destination: section.2 Children: Item: Title: Alterations of FA Metabolism in PCa Destination: subsection.2.1 Children: Item: Title: De Novo FA Synthesis Destination: subsubsection.2.1.1 Item: Title: FA Uptake Destination: subsubsection.2.1.2 Item: Title: FA Oxidation (FAO) Destination: subsubsection.2.1.3 Item: Title: FA Storage and Release Destination: subsubsection.2.1.4 Item: Title: Alterations of Cholesterol Metabolism in PCa Destination: subsection.2.2 Item: Title: Alterations of Phospholipid Metabolism in PCa Destination: subsection.2.3 Item: Title: Targeting Metabolic Vulnerabilities in PCa Destination: subsection.2.4 Item: Title: The Epigenome of PCa Destination: section.3 Children: Item: Title: Alterations of DNA Methylation in PCa Destination: subsection.3.1 Item: Title: Alterations of Histone Modifications in PCa Destination: subsection.3.2 Item: Title: Influence of Diet on PCa, Lipid Metabolism and the Epigenome Destination: section.4 Item: Title: Interaction between Lipid Metabolism and Epigenetics in PCa Destination: section.5 Children: Item: Title: Impact of Lipid Metabolism on Epigenetics Destination: subsection.5.1 Children: Item: Title: FAs, Acetyl-CoA, and Histone Acetylation Destination: subsubsection.5.1.1 Item: Title: SCFAs, Non-Acetyl Acyl-CoAs, and Histone Acylation Destination: subsubsection.5.1.2 Item: Title: SCFAs and Histone Deacetylases Destination: subsubsection.5.1.3 Item: Title: FAs and Sirtuins Destination: subsubsection.5.1.4 Item: Title: Phospholipids, SAM, and Histone Methylation Destination: subsubsection.5.1.5 Item: Title: Nuclear Lipogenic Enzymes Destination: subsubsection.5.1.6 Item: Title: Impact of Epigenetics on Lipid Metabolism Destination: subsection.5.2 Item: Title: Concluding Remarks and Future Directions Destination: section.6 Item: Title: References Destination: section.6 Info: Title: Lipid Metabolism and Epigenetics Crosstalk in Prostate Cancer Author: Juan C. Pardo, Vicenç Ruiz de Porras, Joan Gil, Albert Font, Manel Puig-Domingo and Mireia Jordà Subject: Prostate cancer (PCa) is the most commonly diagnosed malignant neoplasm in men in the Western world. Localized low-risk PCa has an excellent prognosis thanks to effective local treatments; however, despite the incorporation of new therapeutic strategies, metastatic PCa remains incurable mainly due to disease heterogeneity and the development of resistance to therapy. The mechanisms underlying PCa progression and therapy resistance are multiple and include metabolic reprogramming, especially in relation to lipid metabolism, as well as epigenetic remodelling, both of which enable cancer cells to adapt to dynamic changes in the tumour. Interestingly, metabolism and epigenetics are interconnected. Metabolism can regulate epigenetics through the direct influence of metabolites on epigenetic processes, while epigenetics can control metabolism by directly or indirectly regulating the expression of metabolic genes. Moreover, epidemiological studies suggest an association between a high-fat diet, which can alter the availability of metabolites, and PCa progression. Here, we review the alterations of lipid metabolism and epigenetics in PCa, before focusing on the mechanisms that connect them. We also discuss the influence of diet in this scenario. This information may help to identify prognostic and predictive biomarkers as well as targetable vulnerabilities. Keywords: prostate cancer; lipid metabolism; epigenetics; diet; fatty acid; cholesterol; DNA methylation; histone modifications; predictive biomarkers; therapeutic vulnerabilities Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Feb 18 06:55:33 CET 2022 ModDate: Fri Feb 18 07:01:25 CET 2022 ID: 0x85bd8e153cc989ab26df1c745d2ec85a, 0x85bd8e153cc989ab26df1c745d2ec85a Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: WNWTFR+VnURWPalladioL-Bold FontSubset: true FirstChar: 160 LastChar: 160 FontDescriptor: FontName: WNWTFR+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: GOCQIR+EURM10 FontSubset: true FirstChar: 11 LastChar: 13 FontDescriptor: FontName: GOCQIR+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: WOLOAL+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: WOLOAL+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: RIVHWD+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: RIVHWD+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: BCDWAK+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 243 FontDescriptor: FontName: BCDWAK+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: GYREAE+CMSY10 FontSubset: true FirstChar: 0 LastChar: 48 FontDescriptor: FontName: GYREAE+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: HKKCDU+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 231 FontDescriptor: FontName: HKKCDU+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 34, 347, 152, 356 Annotation: Subtype: Link Rect: 34, 337, 72, 344 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 756, 169, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 228, 679, 239, 693 Annotation: Subtype: Link Rect: 293, 679, 304, 693 Annotation: Subtype: Link Rect: 506, 173, 513, 182 ActionDest: 176 Annotation: Subtype: Link Rect: 276, 148, 283, 157 ActionDest: 176 Annotation: Subtype: Link Rect: 405, 73, 412, 82 ActionDest: 176 Annotation: Subtype: Link Rect: 116, 17, 250, 28 Annotation: Subtype: Link Rect: 404, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 420, 86, 439 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 449, 710, 456, 719 ActionDest: 176 Annotation: Subtype: Link Rect: 456, 710, 463, 719 ActionDest: 176 Annotation: Subtype: Link Rect: 436, 660, 443, 669 ActionDest: 176 Annotation: Subtype: Link Rect: 337, 597, 344, 606 ActionDest: 176 Annotation: Subtype: Link Rect: 344, 597, 351, 606 ActionDest: 176 Annotation: Subtype: Link Rect: 541, 572, 548, 581 ActionDest: 176 Annotation: Subtype: Link Rect: 549, 572, 556, 581 ActionDest: 176 Annotation: Subtype: Link Rect: 201, 535, 213, 544 ActionDest: 176 Annotation: Subtype: Link Rect: 216, 535, 227, 544 ActionDest: 176 Annotation: Subtype: Link Rect: 269, 509, 281, 519 ActionDest: 176 Annotation: Subtype: Link Rect: 284, 509, 296, 519 ActionDest: 179 Annotation: Subtype: Link Rect: 367, 510, 379, 519 ActionDest: 179 Annotation: Subtype: Link Rect: 379, 509, 391, 519 ActionDest: 179 Annotation: Subtype: Link Rect: 486, 509, 498, 519 ActionDest: 179 Annotation: Subtype: Link Rect: 237, 459, 249, 468 ActionDest: 179 Annotation: Subtype: Link Rect: 349, 334, 361, 343 ActionDest: 179 Annotation: Subtype: Link Rect: 361, 334, 373, 343 ActionDest: 179 Annotation: Subtype: Link Rect: 242, 309, 254, 318 ActionDest: 179 Annotation: Subtype: Link Rect: 472, 271, 484, 280 ActionDest: 179 Annotation: Subtype: Link Rect: 484, 271, 496, 280 ActionDest: 179 Annotation: Subtype: Link Rect: 445, 258, 457, 267 ActionDest: 179 Annotation: Subtype: Link Rect: 458, 259, 470, 267 ActionDest: 179 Annotation: Subtype: Link Rect: 544, 233, 556, 242 ActionDest: 179 Annotation: Subtype: Link Rect: 344, 183, 356, 192 ActionDest: 179 Annotation: Subtype: Link Rect: 443, 170, 455, 180 ActionDest: 179 Annotation: Subtype: Link Rect: 456, 170, 468, 180 ActionDest: 179 Annotation: Subtype: Link Rect: 356, 158, 368, 167 ActionDest: 179 Annotation: Subtype: Link Rect: 384, 108, 396, 117 ActionDest: 179 Annotation: Subtype: Link Rect: 396, 108, 408, 117 ActionDest: 179 Annotation: Subtype: Link Rect: 318, 70, 330, 79 ActionDest: 179 Annotation: Subtype: Link Rect: 330, 70, 342, 79 ActionDest: 179 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 215, 710, 227, 719 ActionDest: 179 Annotation: Subtype: Link Rect: 389, 497, 401, 506 ActionDest: 179 Annotation: Subtype: Link Rect: 251, 459, 263, 468 ActionDest: 179 Annotation: Subtype: Link Rect: 480, 446, 492, 455 ActionDest: 179 Annotation: Subtype: Link Rect: 340, 371, 352, 380 ActionDest: 183 Annotation: Subtype: Link Rect: 353, 371, 365, 380 ActionDest: 183 Annotation: Subtype: Link Rect: 332, 333, 344, 342 ActionDest: 183 Annotation: Subtype: Link Rect: 549, 306, 556, 318 ActionDest: 89 Annotation: Subtype: Link Rect: 226, 258, 238, 267 ActionDest: 183 Annotation: Subtype: Link Rect: 388, 233, 400, 242 ActionDest: 183 Annotation: Subtype: Link Rect: 447, 218, 454, 230 ActionDest: 89 Annotation: Subtype: Link Rect: 235, 170, 247, 179 ActionDest: 183 Annotation: Subtype: Link Rect: 247, 170, 259, 179 ActionDest: 183 Annotation: Subtype: Link Rect: 411, 158, 423, 167 ActionDest: 183 Annotation: Subtype: Link Rect: 423, 158, 435, 167 ActionDest: 183 Annotation: Subtype: Link Rect: 243, 130, 250, 142 ActionDest: 111 Annotation: Subtype: Link Rect: 257, 133, 269, 142 ActionDest: 183 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 544, 412, 556, 421 ActionDest: 183 Annotation: Subtype: Link Rect: 199, 397, 206, 409 ActionDest: 89 Annotation: Subtype: Link Rect: 450, 337, 462, 346 ActionDest: 183 Annotation: Subtype: Link Rect: 361, 196, 368, 208 ActionDest: 89 Annotation: Subtype: Link Rect: 509, 186, 521, 195 ActionDest: 183 Annotation: Subtype: Link Rect: 219, 148, 231, 158 ActionDest: 183 Page: Sequence: 5 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 362, 393, 374, 402 ActionDest: 183 Annotation: Subtype: Link Rect: 402, 368, 414, 377 ActionDest: 183 Annotation: Subtype: Link Rect: 349, 342, 361, 352 ActionDest: 183 Annotation: Subtype: Link Rect: 346, 315, 353, 327 ActionDest: 89 Annotation: Subtype: Link Rect: 310, 242, 322, 251 ActionDest: 183 Annotation: Subtype: Link Rect: 261, 91, 273, 100 ActionDest: 179 Annotation: Subtype: Link Rect: 274, 91, 286, 100 ActionDest: 183 Annotation: Subtype: Link Rect: 287, 66, 299, 75 ActionDest: 183 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 537, 683, 544, 695 ActionDest: 111 Annotation: Subtype: Link Rect: 544, 673, 556, 682 ActionDest: 179 Annotation: Subtype: Link Rect: 192, 622, 204, 631 ActionDest: 183 Annotation: Subtype: Link Rect: 543, 622, 555, 631 ActionDest: 183 Annotation: Subtype: Link Rect: 412, 610, 424, 619 ActionDest: 183 Annotation: Subtype: Link Rect: 290, 560, 302, 569 ActionDest: 183 Annotation: Subtype: Link Rect: 500, 547, 512, 556 ActionDest: 183 Annotation: Subtype: Link Rect: 218, 522, 230, 531 ActionDest: 183 Annotation: Subtype: Link Rect: 520, 471, 532, 481 ActionDest: 183 Annotation: Subtype: Link Rect: 327, 431, 334, 443 ActionDest: 111 Annotation: Subtype: Link Rect: 342, 434, 354, 443 ActionDest: 179 Annotation: Subtype: Link Rect: 325, 409, 337, 418 ActionDest: 183 Annotation: Subtype: Link Rect: 217, 384, 229, 393 ActionDest: 186 Annotation: Subtype: Link Rect: 229, 384, 241, 393 ActionDest: 186 Annotation: Subtype: Link Rect: 332, 384, 344, 393 ActionDest: 186 Annotation: Subtype: Link Rect: 472, 321, 484, 330 ActionDest: 186 Annotation: Subtype: Link Rect: 543, 308, 555, 317 ActionDest: 186 Annotation: Subtype: Link Rect: 408, 283, 420, 292 ActionDest: 186 Annotation: Subtype: Link Rect: 197, 258, 209, 267 ActionDest: 186 Annotation: Subtype: Link Rect: 524, 258, 536, 267 ActionDest: 186 Annotation: Subtype: Link Rect: 191, 221, 203, 229 ActionDest: 186 Annotation: Subtype: Link Rect: 455, 208, 467, 217 ActionDest: 186 Annotation: Subtype: Link Rect: 324, 183, 336, 192 ActionDest: 186 Annotation: Subtype: Link Rect: 200, 170, 212, 179 ActionDest: 186 Annotation: Subtype: Link Rect: 213, 170, 225, 179 ActionDest: 186 Annotation: Subtype: Link Rect: 267, 145, 279, 154 ActionDest: 186 Annotation: Subtype: Link Rect: 354, 120, 366, 129 ActionDest: 179 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 544, 710, 556, 719 ActionDest: 186 Annotation: Subtype: Link Rect: 544, 685, 556, 694 ActionDest: 186 Annotation: Subtype: Link Rect: 491, 620, 498, 632 ActionDest: 111 Annotation: Subtype: Link Rect: 428, 597, 440, 606 ActionDest: 186 Annotation: Subtype: Link Rect: 229, 585, 241, 594 ActionDest: 179 Annotation: Subtype: Link Rect: 407, 560, 419, 569 ActionDest: 186 Annotation: Subtype: Link Rect: 474, 484, 486, 493 ActionDest: 186 Annotation: Subtype: Link Rect: 409, 421, 421, 430 ActionDest: 186 Annotation: Subtype: Link Rect: 391, 384, 403, 393 ActionDest: 186 Annotation: Subtype: Link Rect: 379, 358, 391, 368 ActionDest: 186 Annotation: Subtype: Link Rect: 476, 346, 488, 355 ActionDest: 186 Annotation: Subtype: Link Rect: 222, 306, 229, 318 ActionDest: 111 Annotation: Subtype: Link Rect: 409, 283, 421, 292 ActionDest: 186 Annotation: Subtype: Link Rect: 354, 245, 366, 255 ActionDest: 186 Annotation: Subtype: Link Rect: 467, 233, 479, 242 ActionDest: 186 Annotation: Subtype: Link Rect: 480, 233, 492, 242 ActionDest: 186 Annotation: Subtype: Link Rect: 433, 208, 445, 217 ActionDest: 189 Annotation: Subtype: Link Rect: 301, 183, 313, 192 ActionDest: 189 Annotation: Subtype: Link Rect: 291, 158, 303, 167 ActionDest: 189 Annotation: Subtype: Link Rect: 296, 120, 308, 129 ActionDest: 189 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 269, 695, 281, 704 ActionDest: 189 Annotation: Subtype: Link Rect: 435, 657, 447, 666 ActionDest: 189 Annotation: Subtype: Link Rect: 437, 607, 449, 616 ActionDest: 189 Annotation: Subtype: Link Rect: 189, 594, 201, 603 ActionDest: 189 Annotation: Subtype: Link Rect: 415, 579, 422, 591 ActionDest: 111 Annotation: Subtype: Link Rect: 395, 506, 412, 516 ActionDest: 189 Annotation: Subtype: Link Rect: 455, 481, 472, 490 ActionDest: 189 Annotation: Subtype: Link Rect: 264, 444, 281, 453 ActionDest: 189 Annotation: Subtype: Link Rect: 292, 419, 309, 428 ActionDest: 189 Annotation: Subtype: Link Rect: 313, 393, 330, 403 ActionDest: 189 Annotation: Subtype: Link Rect: 312, 356, 324, 365 ActionDest: 189 Annotation: Subtype: Link Rect: 324, 356, 341, 365 ActionDest: 189 Annotation: Subtype: Link Rect: 226, 331, 243, 340 ActionDest: 189 Annotation: Subtype: Link Rect: 263, 280, 280, 290 ActionDest: 189 Annotation: Subtype: Link Rect: 525, 230, 541, 239 ActionDest: 189 Annotation: Subtype: Link Rect: 518, 217, 535, 227 ActionDest: 189 Annotation: Subtype: Link Rect: 180, 142, 192, 151 ActionDest: 179 Annotation: Subtype: Link Rect: 188, 104, 205, 114 ActionDest: 189 Annotation: Subtype: Link Rect: 320, 67, 337, 76 ActionDest: 189 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 496, 723, 513, 732 ActionDest: 189 Annotation: Subtype: Link Rect: 513, 723, 530, 732 ActionDest: 189 Annotation: Subtype: Link Rect: 257, 673, 274, 682 ActionDest: 189 Annotation: Subtype: Link Rect: 274, 673, 291, 682 ActionDest: 189 Annotation: Subtype: Link Rect: 313, 648, 330, 657 ActionDest: 189 Annotation: Subtype: Link Rect: 331, 648, 348, 657 ActionDest: 189 Annotation: Subtype: Link Rect: 249, 620, 256, 632 ActionDest: 111 Annotation: Subtype: Link Rect: 305, 610, 322, 619 ActionDest: 189 Annotation: Subtype: Link Rect: 198, 597, 215, 606 ActionDest: 189 Annotation: Subtype: Link Rect: 303, 572, 320, 581 ActionDest: 189 Annotation: Subtype: Link Rect: 228, 547, 245, 556 ActionDest: 189 Annotation: Subtype: Link Rect: 535, 510, 552, 519 ActionDest: 189 Annotation: Subtype: Link Rect: 459, 356, 466, 368 ActionDest: 145 Annotation: Subtype: Link Rect: 467, 263, 479, 270 ActionDest: 192 Annotation: Subtype: Link Rect: 467, 242, 479, 249 ActionDest: 192 Annotation: Subtype: Link Rect: 467, 94, 479, 101 ActionDest: 192 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 467, 674, 479, 681 ActionDest: 192 Annotation: Subtype: Link Rect: 430, 363, 447, 372 ActionDest: 192 Annotation: Subtype: Link Rect: 227, 288, 244, 297 ActionDest: 192 Annotation: Subtype: Link Rect: 247, 287, 264, 297 ActionDest: 192 Annotation: Subtype: Link Rect: 512, 237, 524, 246 ActionDest: 179 Annotation: Subtype: Link Rect: 525, 237, 537, 246 ActionDest: 179 Annotation: Subtype: Link Rect: 440, 225, 457, 234 ActionDest: 192 Annotation: Subtype: Link Rect: 458, 225, 475, 234 ActionDest: 192 Annotation: Subtype: Link Rect: 334, 200, 351, 209 ActionDest: 192 Annotation: Subtype: Link Rect: 213, 137, 225, 146 ActionDest: 179 Annotation: Subtype: Link Rect: 239, 87, 251, 96 ActionDest: 179 Annotation: Subtype: Link Rect: 251, 87, 268, 96 ActionDest: 192 Annotation: Subtype: Link Rect: 284, 74, 296, 83 ActionDest: 179 Annotation: Subtype: Link Rect: 296, 74, 313, 83 ActionDest: 192 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 234, 723, 251, 732 ActionDest: 192 Annotation: Subtype: Link Rect: 251, 723, 268, 732 ActionDest: 192 Annotation: Subtype: Link Rect: 264, 660, 280, 669 ActionDest: 192 Annotation: Subtype: Link Rect: 281, 660, 298, 669 ActionDest: 192 Annotation: Subtype: Link Rect: 532, 610, 549, 619 ActionDest: 192 Annotation: Subtype: Link Rect: 402, 584, 414, 594 ActionDest: 179 Annotation: Subtype: Link Rect: 414, 585, 426, 594 ActionDest: 179 Annotation: Subtype: Link Rect: 323, 471, 340, 481 ActionDest: 192 Annotation: Subtype: Link Rect: 286, 446, 303, 455 ActionDest: 192 Annotation: Subtype: Link Rect: 303, 447, 320, 455 ActionDest: 192 Annotation: Subtype: Link Rect: 206, 434, 223, 443 ActionDest: 192 Annotation: Subtype: Link Rect: 251, 421, 268, 430 ActionDest: 192 Annotation: Subtype: Link Rect: 233, 358, 250, 368 ActionDest: 192 Annotation: Subtype: Link Rect: 251, 359, 267, 368 ActionDest: 192 Annotation: Subtype: Link Rect: 271, 359, 287, 368 ActionDest: 192 Annotation: Subtype: Link Rect: 346, 346, 363, 355 ActionDest: 195 Annotation: Subtype: Link Rect: 262, 321, 279, 330 ActionDest: 192 Annotation: Subtype: Link Rect: 455, 283, 472, 292 ActionDest: 192 Annotation: Subtype: Link Rect: 472, 283, 489, 292 ActionDest: 192 Annotation: Subtype: Link Rect: 492, 283, 509, 292 ActionDest: 192 Annotation: Subtype: Link Rect: 197, 233, 214, 242 ActionDest: 195 Annotation: Subtype: Link Rect: 214, 233, 231, 242 ActionDest: 195 Annotation: Subtype: Link Rect: 522, 233, 538, 242 ActionDest: 195 Annotation: Subtype: Link Rect: 539, 233, 556, 242 ActionDest: 195 Annotation: Subtype: Link Rect: 349, 170, 366, 179 ActionDest: 192 Annotation: Subtype: Link Rect: 518, 120, 535, 129 ActionDest: 195 Annotation: Subtype: Link Rect: 267, 95, 284, 104 ActionDest: 195 Annotation: Subtype: Link Rect: 287, 95, 304, 104 ActionDest: 195 Annotation: Subtype: Link Rect: 539, 95, 556, 104 ActionDest: 192 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 310, 660, 327, 669 ActionDest: 195 Annotation: Subtype: Link Rect: 313, 597, 330, 606 ActionDest: 192 Annotation: Subtype: Link Rect: 202, 471, 219, 481 ActionDest: 195 Annotation: Subtype: Link Rect: 197, 446, 214, 455 ActionDest: 195 Annotation: Subtype: Link Rect: 215, 446, 232, 455 ActionDest: 195 Annotation: Subtype: Link Rect: 233, 434, 250, 443 ActionDest: 195 Annotation: Subtype: Link Rect: 254, 371, 271, 380 ActionDest: 195 Annotation: Subtype: Link Rect: 271, 371, 288, 380 ActionDest: 195 Annotation: Subtype: Link Rect: 203, 346, 220, 355 ActionDest: 192 Annotation: Subtype: Link Rect: 220, 346, 237, 355 ActionDest: 192 Annotation: Subtype: Link Rect: 238, 346, 255, 355 ActionDest: 195 Annotation: Subtype: Link Rect: 518, 346, 535, 355 ActionDest: 195 Annotation: Subtype: Link Rect: 493, 333, 510, 342 ActionDest: 195 Annotation: Subtype: Link Rect: 188, 308, 205, 317 ActionDest: 195 Annotation: Subtype: Link Rect: 316, 296, 333, 305 ActionDest: 195 Annotation: Subtype: Link Rect: 484, 233, 501, 242 ActionDest: 195 Annotation: Subtype: Link Rect: 330, 208, 347, 217 ActionDest: 195 Annotation: Subtype: Link Rect: 340, 158, 357, 167 ActionDest: 192 Annotation: Subtype: Link Rect: 358, 158, 375, 167 ActionDest: 195 Annotation: Subtype: Link Rect: 300, 133, 317, 142 ActionDest: 192 Annotation: Subtype: Link Rect: 290, 70, 307, 79 ActionDest: 198 Annotation: Subtype: Link Rect: 310, 69, 327, 79 ActionDest: 198 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 327, 736, 344, 744 ActionDest: 198 Annotation: Subtype: Link Rect: 324, 723, 336, 732 ActionDest: 189 Annotation: Subtype: Link Rect: 247, 698, 264, 707 ActionDest: 189 Annotation: Subtype: Link Rect: 493, 673, 510, 682 ActionDest: 198 Annotation: Subtype: Link Rect: 267, 610, 284, 619 ActionDest: 198 Annotation: Subtype: Link Rect: 287, 610, 304, 619 ActionDest: 198 Annotation: Subtype: Link Rect: 277, 597, 294, 606 ActionDest: 198 Annotation: Subtype: Link Rect: 441, 585, 453, 594 ActionDest: 183 Annotation: Subtype: Link Rect: 454, 585, 470, 594 ActionDest: 198 Annotation: Subtype: Link Rect: 336, 509, 353, 519 ActionDest: 198 Annotation: Subtype: Link Rect: 495, 484, 507, 493 ActionDest: 186 Annotation: Subtype: Link Rect: 539, 459, 556, 468 ActionDest: 198 Annotation: Subtype: Link Rect: 510, 434, 522, 443 ActionDest: 183 Annotation: Subtype: Link Rect: 216, 396, 233, 406 ActionDest: 198 Annotation: Subtype: Link Rect: 203, 233, 220, 242 ActionDest: 198 Annotation: Subtype: Link Rect: 314, 183, 331, 192 ActionDest: 198 Annotation: Subtype: Link Rect: 334, 183, 351, 192 ActionDest: 198 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 219, 621, 236, 630 ActionDest: 198 Annotation: Subtype: Link Rect: 406, 533, 423, 542 ActionDest: 198 Annotation: Subtype: Link Rect: 189, 508, 206, 517 ActionDest: 195 Annotation: Subtype: Link Rect: 206, 508, 223, 517 ActionDest: 195 Annotation: Subtype: Link Rect: 313, 471, 330, 480 ActionDest: 198 Annotation: Subtype: Link Rect: 333, 471, 350, 480 ActionDest: 198 Annotation: Subtype: Link Rect: 312, 445, 329, 455 ActionDest: 198 Annotation: Subtype: Link Rect: 301, 408, 318, 417 ActionDest: 198 Annotation: Subtype: Link Rect: 291, 330, 298, 342 ActionDest: 111 Annotation: Subtype: Link Rect: 305, 332, 322, 342 ActionDest: 198 Annotation: Subtype: Link Rect: 523, 282, 540, 291 ActionDest: 198 Annotation: Subtype: Link Rect: 350, 204, 357, 216 ActionDest: 111 Annotation: Subtype: Link Rect: 234, 182, 246, 191 ActionDest: 186 Annotation: Subtype: Link Rect: 538, 157, 555, 166 ActionDest: 198 Annotation: Subtype: Link Rect: 378, 69, 395, 78 ActionDest: 198 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 189, 710, 206, 719 ActionDest: 198 Annotation: Subtype: Link Rect: 343, 610, 359, 619 ActionDest: 201 Annotation: Subtype: Link Rect: 216, 585, 232, 594 ActionDest: 198 Annotation: Subtype: Link Rect: 396, 547, 413, 556 ActionDest: 201 Annotation: Subtype: Link Rect: 196, 497, 213, 506 ActionDest: 198 Annotation: Subtype: Link Rect: 361, 472, 378, 481 ActionDest: 201 Annotation: Subtype: Link Rect: 401, 333, 418, 342 ActionDest: 201 Annotation: Subtype: Link Rect: 281, 296, 298, 305 ActionDest: 201 Annotation: Subtype: Link Rect: 197, 245, 214, 255 ActionDest: 201 Annotation: Subtype: Link Rect: 499, 220, 516, 229 ActionDest: 201 Annotation: Subtype: Link Rect: 345, 170, 362, 179 ActionDest: 201 Annotation: Subtype: Link Rect: 363, 170, 380, 179 ActionDest: 201 Annotation: Subtype: Link Rect: 519, 120, 536, 129 ActionDest: 201 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 396, 723, 413, 732 ActionDest: 201 Annotation: Subtype: Link Rect: 502, 672, 519, 681 ActionDest: 201 Annotation: Subtype: Link Rect: 326, 622, 343, 631 ActionDest: 201 Annotation: Subtype: Link Rect: 346, 622, 363, 631 ActionDest: 201 Annotation: Subtype: Link Rect: 433, 560, 450, 568 ActionDest: 201 Annotation: Subtype: Link Rect: 330, 459, 347, 468 ActionDest: 201 Annotation: Subtype: Link Rect: 350, 459, 367, 468 ActionDest: 201 Annotation: Subtype: Link Rect: 464, 396, 481, 405 ActionDest: 201 Annotation: Subtype: Link Rect: 481, 396, 498, 405 ActionDest: 201 Annotation: Subtype: Link Rect: 287, 358, 304, 367 ActionDest: 201 Annotation: Subtype: Link Rect: 200, 308, 217, 317 ActionDest: 201 Annotation: Subtype: Link Rect: 364, 283, 381, 292 ActionDest: 201 Annotation: Subtype: Link Rect: 382, 283, 399, 292 ActionDest: 201 Annotation: Subtype: Link Rect: 539, 270, 556, 279 ActionDest: 201 Annotation: Subtype: Link Rect: 297, 220, 314, 229 ActionDest: 201 Annotation: Subtype: Link Rect: 221, 182, 237, 192 ActionDest: 201 Annotation: Subtype: Link Rect: 413, 183, 430, 192 ActionDest: 204 Annotation: Subtype: Link Rect: 507, 145, 524, 154 ActionDest: 204 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 380, 735, 397, 744 ActionDest: 204 Annotation: Subtype: Link Rect: 539, 710, 556, 719 ActionDest: 204 Annotation: Subtype: Link Rect: 539, 698, 556, 707 ActionDest: 204 Annotation: Subtype: Link Rect: 517, 647, 534, 657 ActionDest: 204 Annotation: Subtype: Link Rect: 358, 497, 375, 506 ActionDest: 204 Annotation: Subtype: Link Rect: 195, 446, 212, 455 ActionDest: 204 Annotation: Subtype: Link Rect: 539, 384, 556, 393 ActionDest: 189 Annotation: Subtype: Link Rect: 190, 308, 207, 317 ActionDest: 204 Annotation: Subtype: Link Rect: 499, 192, 506, 204 ActionDest: 111 Annotation: Subtype: Link Rect: 480, 170, 497, 179 ActionDest: 204 Annotation: Subtype: Link Rect: 276, 132, 293, 141 ActionDest: 204 Annotation: Subtype: Link Rect: 518, 94, 535, 103 ActionDest: 204 Annotation: Subtype: Link Rect: 246, 69, 262, 78 ActionDest: 204 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 324, 698, 341, 707 ActionDest: 204 Annotation: Subtype: Link Rect: 539, 685, 556, 694 ActionDest: 204 Annotation: Subtype: Link Rect: 387, 622, 404, 631 ActionDest: 204 Annotation: Subtype: Link Rect: 476, 547, 493, 556 ActionDest: 204 Annotation: Subtype: Link Rect: 415, 522, 432, 531 ActionDest: 204 Annotation: Subtype: Link Rect: 363, 472, 380, 481 ActionDest: 204 Annotation: Subtype: Link Rect: 380, 472, 397, 481 ActionDest: 204 Annotation: Subtype: Link Rect: 310, 434, 327, 443 ActionDest: 204 Annotation: Subtype: Link Rect: 371, 397, 388, 406 ActionDest: 204 Annotation: Subtype: Link Rect: 368, 384, 385, 393 ActionDest: 204 Annotation: Subtype: Link Rect: 386, 384, 403, 393 ActionDest: 204 Annotation: Subtype: Link Rect: 378, 284, 395, 293 ActionDest: 204 Annotation: Subtype: Link Rect: 408, 221, 425, 230 ActionDest: 204 Annotation: Subtype: Link Rect: 347, 196, 364, 205 ActionDest: 204 Page: Sequence: 20 Annotations: Annotation: Subtype: Link Rect: 468, 376, 505, 387 Annotation: Subtype: Link Rect: 511, 376, 547, 387 Annotation: Subtype: Link Rect: 355, 365, 392, 376 Annotation: Subtype: Link Rect: 399, 365, 435, 376 Annotation: Subtype: Link Rect: 59, 343, 96, 353 Annotation: Subtype: Link Rect: 389, 307, 427, 318 Annotation: Subtype: Link Rect: 433, 307, 469, 318 Annotation: Subtype: Link Rect: 205, 274, 242, 284 Annotation: Subtype: Link Rect: 520, 261, 557, 272 Annotation: Subtype: Link Rect: 127, 239, 164, 249 Annotation: Subtype: Link Rect: 401, 227, 439, 238 Annotation: Subtype: Link Rect: 338, 192, 376, 203 Annotation: Subtype: Link Rect: 466, 169, 503, 180 Annotation: Subtype: Link Rect: 519, 146, 557, 157 Annotation: Subtype: Link Rect: 59, 136, 95, 146 Annotation: Subtype: Link Rect: 95, 101, 133, 111 Annotation: Subtype: Link Rect: 139, 101, 175, 111 Annotation: Subtype: Link Rect: 59, 67, 96, 77 Annotation: Subtype: Link Rect: 102, 67, 138, 77 Page: Sequence: 21 Annotations: Annotation: Subtype: Link Rect: 59, 711, 96, 721 Annotation: Subtype: Link Rect: 102, 711, 138, 721 Annotation: Subtype: Link Rect: 519, 687, 557, 698 Annotation: Subtype: Link Rect: 59, 676, 95, 687 Annotation: Subtype: Link Rect: 59, 642, 96, 652 Annotation: Subtype: Link Rect: 518, 618, 555, 629 Annotation: Subtype: Link Rect: 86, 584, 123, 594 Annotation: Subtype: Link Rect: 487, 560, 524, 571 Annotation: Subtype: Link Rect: 190, 538, 228, 548 Annotation: Subtype: Link Rect: 127, 515, 164, 525 Annotation: Subtype: Link Rect: 170, 515, 206, 525 Annotation: Subtype: Link Rect: 59, 492, 96, 502 Annotation: Subtype: Link Rect: 102, 492, 138, 502 Annotation: Subtype: Link Rect: 95, 458, 133, 468 Annotation: Subtype: Link Rect: 139, 458, 175, 468 Annotation: Subtype: Link Rect: 167, 435, 204, 445 Annotation: Subtype: Link Rect: 211, 435, 247, 445 Annotation: Subtype: Link Rect: 91, 412, 128, 422 Annotation: Subtype: Link Rect: 59, 389, 96, 399 Annotation: Subtype: Link Rect: 131, 366, 168, 376 Annotation: Subtype: Link Rect: 135, 343, 173, 353 Annotation: Subtype: Link Rect: 199, 319, 236, 330 Annotation: Subtype: Link Rect: 59, 285, 96, 295 Annotation: Subtype: Link Rect: 461, 261, 499, 272 Annotation: Subtype: Link Rect: 505, 261, 541, 272 Annotation: Subtype: Link Rect: 462, 238, 499, 249 Annotation: Subtype: Link Rect: 505, 238, 542, 249 Annotation: Subtype: Link Rect: 519, 215, 557, 226 Annotation: Subtype: Link Rect: 59, 205, 95, 215 Annotation: Subtype: Link Rect: 95, 182, 133, 192 Annotation: Subtype: Link Rect: 139, 182, 175, 192 Annotation: Subtype: Link Rect: 323, 158, 361, 169 Annotation: Subtype: Link Rect: 514, 146, 551, 157 Annotation: Subtype: Link Rect: 488, 135, 525, 146 Annotation: Subtype: Link Rect: 59, 113, 96, 123 Annotation: Subtype: Link Rect: 441, 89, 479, 100 Annotation: Subtype: Link Rect: 444, 77, 482, 88 Page: Sequence: 22 Annotations: Annotation: Subtype: Link Rect: 159, 722, 196, 733 Annotation: Subtype: Link Rect: 202, 722, 238, 733 Annotation: Subtype: Link Rect: 478, 710, 515, 721 Annotation: Subtype: Link Rect: 521, 710, 557, 721 Annotation: Subtype: Link Rect: 95, 688, 133, 698 Annotation: Subtype: Link Rect: 163, 665, 200, 675 Annotation: Subtype: Link Rect: 206, 665, 242, 675 Annotation: Subtype: Link Rect: 327, 642, 365, 652 Annotation: Subtype: Link Rect: 183, 607, 220, 617 Annotation: Subtype: Link Rect: 152, 573, 190, 583 Annotation: Subtype: Link Rect: 353, 549, 391, 560 Annotation: Subtype: Link Rect: 86, 515, 124, 525 Annotation: Subtype: Link Rect: 158, 491, 196, 502 Annotation: Subtype: Link Rect: 140, 458, 177, 468 Annotation: Subtype: Link Rect: 184, 458, 220, 468 Annotation: Subtype: Link Rect: 275, 434, 312, 445 Annotation: Subtype: Link Rect: 353, 411, 390, 422 Annotation: Subtype: Link Rect: 397, 411, 433, 422 Annotation: Subtype: Link Rect: 460, 388, 498, 399 Annotation: Subtype: Link Rect: 504, 388, 540, 399 Annotation: Subtype: Link Rect: 59, 354, 96, 364 Annotation: Subtype: Link Rect: 102, 354, 138, 364 Annotation: Subtype: Link Rect: 519, 342, 557, 353 Annotation: Subtype: Link Rect: 59, 331, 95, 341 Annotation: Subtype: Link Rect: 504, 319, 542, 330 Annotation: Subtype: Link Rect: 487, 296, 525, 307 Annotation: Subtype: Link Rect: 352, 261, 390, 272 Annotation: Subtype: Link Rect: 185, 228, 223, 238 Annotation: Subtype: Link Rect: 156, 193, 193, 203 Annotation: Subtype: Link Rect: 200, 193, 236, 203 Annotation: Subtype: Link Rect: 276, 158, 313, 169 Annotation: Subtype: Link Rect: 319, 158, 355, 169 Annotation: Subtype: Link Rect: 59, 136, 96, 146 Annotation: Subtype: Link Rect: 102, 136, 138, 146 Annotation: Subtype: Link Rect: 341, 100, 378, 111 Annotation: Subtype: Link Rect: 346, 77, 384, 88 Page: Sequence: 23 Annotations: Annotation: Subtype: Link Rect: 59, 711, 96, 721 Annotation: Subtype: Link Rect: 487, 687, 525, 698 Annotation: Subtype: Link Rect: 467, 664, 504, 675 Annotation: Subtype: Link Rect: 520, 641, 557, 652 Annotation: Subtype: Link Rect: 373, 618, 411, 629 Annotation: Subtype: Link Rect: 131, 596, 168, 606 Annotation: Subtype: Link Rect: 175, 596, 211, 606 Annotation: Subtype: Link Rect: 333, 572, 369, 583 Annotation: Subtype: Link Rect: 113, 550, 150, 560 Annotation: Subtype: Link Rect: 156, 550, 192, 560 Annotation: Subtype: Link Rect: 363, 526, 400, 537 Annotation: Subtype: Link Rect: 95, 504, 133, 514 Annotation: Subtype: Link Rect: 59, 469, 96, 479 Annotation: Subtype: Link Rect: 418, 445, 455, 456 Annotation: Subtype: Link Rect: 59, 412, 96, 422 Annotation: Subtype: Link Rect: 493, 388, 530, 399 Annotation: Subtype: Link Rect: 59, 366, 96, 376 Annotation: Subtype: Link Rect: 321, 343, 358, 353 Annotation: Subtype: Link Rect: 365, 343, 401, 353 Annotation: Subtype: Link Rect: 131, 308, 168, 318 Annotation: Subtype: Link Rect: 175, 308, 211, 318 Annotation: Subtype: Link Rect: 519, 284, 557, 295 Annotation: Subtype: Link Rect: 59, 274, 95, 284 Annotation: Subtype: Link Rect: 188, 238, 226, 249 Annotation: Subtype: Link Rect: 495, 227, 532, 238 Annotation: Subtype: Link Rect: 341, 204, 378, 215 Annotation: Subtype: Link Rect: 520, 192, 557, 203 Annotation: Subtype: Link Rect: 170, 170, 208, 180 Annotation: Subtype: Link Rect: 113, 136, 151, 146 Annotation: Subtype: Link Rect: 307, 112, 345, 123 Annotation: Subtype: Link Rect: 331, 89, 368, 100 Annotation: Subtype: Link Rect: 374, 89, 410, 100 Annotation: Subtype: Link Rect: 308, 66, 346, 77 Page: Sequence: 24 Annotations: Annotation: Subtype: Link Rect: 413, 722, 451, 733 Annotation: Subtype: Link Rect: 457, 722, 493, 733 Annotation: Subtype: Link Rect: 345, 687, 383, 698 Annotation: Subtype: Link Rect: 389, 687, 425, 698 Annotation: Subtype: Link Rect: 285, 664, 323, 675 Annotation: Subtype: Link Rect: 95, 630, 133, 640 Annotation: Subtype: Link Rect: 139, 630, 175, 640 Annotation: Subtype: Link Rect: 495, 618, 532, 629 Annotation: Subtype: Link Rect: 95, 596, 132, 606 Annotation: Subtype: Link Rect: 514, 583, 552, 594 Annotation: Subtype: Link Rect: 178, 549, 216, 560 Annotation: Subtype: Link Rect: 439, 537, 477, 548 Annotation: Subtype: Link Rect: 483, 537, 519, 548 Annotation: Subtype: Link Rect: 397, 514, 435, 525 Annotation: Subtype: Link Rect: 441, 514, 477, 525 Annotation: Subtype: Link Rect: 204, 480, 241, 491 Annotation: Subtype: Link Rect: 247, 480, 283, 491 Annotation: Subtype: Link Rect: 108, 446, 146, 456 Annotation: Subtype: Link Rect: 268, 412, 305, 422 Annotation: Subtype: Link Rect: 204, 389, 241, 399 Annotation: Subtype: Link Rect: 111, 354, 148, 364 Annotation: Subtype: Link Rect: 513, 342, 551, 353 Annotation: Subtype: Link Rect: 405, 307, 442, 318 Annotation: Subtype: Link Rect: 59, 285, 96, 295 Annotation: Subtype: Link Rect: 478, 273, 515, 284 Annotation: Subtype: Link Rect: 521, 273, 557, 284 Annotation: Subtype: Link Rect: 463, 238, 500, 249 Annotation: Subtype: Link Rect: 506, 238, 542, 249 Annotation: Subtype: Link Rect: 244, 216, 282, 226 Annotation: Subtype: Link Rect: 288, 216, 324, 226 Annotation: Subtype: Link Rect: 95, 193, 132, 203 Annotation: Subtype: Link Rect: 327, 158, 364, 169 Annotation: Subtype: Link Rect: 59, 124, 96, 134 Annotation: Subtype: Link Rect: 493, 100, 531, 111 Annotation: Subtype: Link Rect: 405, 77, 443, 88 Page: Sequence: 25 Annotations: Annotation: Subtype: Link Rect: 127, 711, 164, 721 Annotation: Subtype: Link Rect: 361, 688, 398, 698 Annotation: Subtype: Link Rect: 131, 653, 168, 664 Annotation: Subtype: Link Rect: 175, 653, 211, 664 Annotation: Subtype: Link Rect: 418, 619, 455, 629 Annotation: Subtype: Link Rect: 461, 619, 497, 629 Annotation: Subtype: Link Rect: 458, 606, 496, 617 Annotation: Subtype: Link Rect: 487, 595, 524, 606 Annotation: Subtype: Link Rect: 509, 583, 546, 594 Annotation: Subtype: Link Rect: 470, 572, 507, 583 Annotation: Subtype: Link Rect: 479, 560, 516, 571 Annotation: Subtype: Link Rect: 195, 538, 232, 548 Annotation: Subtype: Link Rect: 502, 514, 539, 525 Annotation: Subtype: Link Rect: 278, 491, 315, 502 Annotation: Subtype: Link Rect: 199, 468, 237, 479 Annotation: Subtype: Link Rect: 243, 468, 279, 479 Annotation: Subtype: Link Rect: 185, 446, 223, 456 Annotation: Subtype: Link Rect: 229, 446, 265, 456 Annotation: Subtype: Link Rect: 95, 412, 133, 422 Annotation: Subtype: Link Rect: 171, 377, 208, 387 Annotation: Subtype: Link Rect: 215, 377, 251, 387 Annotation: Subtype: Link Rect: 86, 343, 124, 353 Annotation: Subtype: Link Rect: 130, 343, 166, 353 Annotation: Subtype: Link Rect: 401, 330, 438, 341 Annotation: Subtype: Link Rect: 514, 319, 551, 330 Annotation: Subtype: Link Rect: 99, 297, 137, 307 Annotation: Subtype: Link Rect: 269, 274, 306, 284 Annotation: Subtype: Link Rect: 104, 239, 142, 249 Annotation: Subtype: Link Rect: 59, 205, 96, 215 Annotation: Subtype: Link Rect: 102, 205, 138, 215 Annotation: Subtype: Link Rect: 384, 181, 421, 192 Annotation: Subtype: Link Rect: 427, 181, 463, 192 Annotation: Subtype: Link Rect: 359, 158, 397, 169 Annotation: Subtype: Link Rect: 403, 158, 439, 169 Annotation: Subtype: Link Rect: 233, 135, 270, 146 Annotation: Subtype: Link Rect: 276, 135, 312, 146 Annotation: Subtype: Link Rect: 378, 112, 416, 123 Annotation: Subtype: Link Rect: 206, 66, 244, 77 Page: Sequence: 26 Annotations: Annotation: Subtype: Link Rect: 59, 711, 96, 721 Annotation: Subtype: Link Rect: 225, 676, 262, 687 Annotation: Subtype: Link Rect: 86, 642, 124, 652 Annotation: Subtype: Link Rect: 500, 618, 537, 629 Annotation: Subtype: Link Rect: 104, 596, 140, 606 Annotation: Subtype: Link Rect: 185, 561, 223, 571 Annotation: Subtype: Link Rect: 229, 561, 265, 571 Annotation: Subtype: Link Rect: 243, 538, 281, 548 Annotation: Subtype: Link Rect: 287, 538, 323, 548 Annotation: Subtype: Link Rect: 59, 504, 96, 514 Annotation: Subtype: Link Rect: 316, 468, 354, 479 Annotation: Subtype: Link Rect: 439, 457, 477, 468 Annotation: Subtype: Link Rect: 399, 411, 436, 422 Annotation: Subtype: Link Rect: 520, 386, 557, 400 Annotation: Subtype: Link Rect: 59, 353, 96, 363 Annotation: Subtype: Link Rect: 149, 319, 187, 329 Annotation: Subtype: Link Rect: 193, 319, 229, 329 Annotation: Subtype: Link Rect: 519, 295, 557, 306 Annotation: Subtype: Link Rect: 59, 284, 95, 294 Annotation: Subtype: Link Rect: 145, 260, 183, 271 Annotation: Subtype: Link Rect: 189, 260, 225, 271 Annotation: Subtype: Link Rect: 341, 226, 378, 237 Annotation: Subtype: Link Rect: 385, 226, 421, 237 Annotation: Subtype: Link Rect: 520, 203, 557, 214 Annotation: Subtype: Link Rect: 59, 192, 95, 202 Annotation: Subtype: Link Rect: 388, 180, 426, 191 Annotation: Subtype: Link Rect: 95, 146, 133, 156 Annotation: Subtype: Link Rect: 367, 122, 405, 133 Annotation: Subtype: Link Rect: 127, 88, 164, 99 Page: Sequence: 27 Annotations: Annotation: Subtype: Link Rect: 248, 711, 286, 721 Annotation: Subtype: Link Rect: 337, 687, 375, 698 Annotation: Subtype: Link Rect: 254, 664, 291, 675 Annotation: Subtype: Link Rect: 298, 664, 334, 675 Annotation: Subtype: Link Rect: 140, 642, 177, 652 Annotation: Subtype: Link Rect: 184, 642, 220, 652 Annotation: Subtype: Link Rect: 59, 619, 96, 629 Annotation: Subtype: Link Rect: 102, 619, 138, 629 Annotation: Subtype: Link Rect: 366, 596, 403, 606 Annotation: Subtype: Link Rect: 409, 596, 445, 606 Annotation: Subtype: Link Rect: 152, 573, 189, 583 Annotation: Subtype: Link Rect: 195, 573, 231, 583 Annotation: Subtype: Link Rect: 59, 550, 96, 560 Annotation: Subtype: Link Rect: 504, 537, 541, 548 Annotation: Subtype: Link Rect: 438, 514, 475, 525 Annotation: Subtype: Link Rect: 388, 491, 426, 502 Annotation: Subtype: Link Rect: 314, 468, 351, 479 Annotation: Subtype: Link Rect: 358, 468, 394, 479 Annotation: Subtype: Link Rect: 466, 445, 503, 456 Annotation: Subtype: Link Rect: 509, 445, 545, 456 Annotation: Subtype: Link Rect: 118, 412, 155, 422 Annotation: Subtype: Link Rect: 161, 412, 197, 422 Annotation: Subtype: Link Rect: 207, 388, 245, 399 Annotation: Subtype: Link Rect: 251, 388, 287, 399 Annotation: Subtype: Link Rect: 173, 366, 211, 376 Annotation: Subtype: Link Rect: 217, 366, 253, 376 Annotation: Subtype: Link Rect: 131, 343, 168, 353 Annotation: Subtype: Link Rect: 95, 320, 132, 330 Annotation: Subtype: Link Rect: 445, 307, 483, 318 Annotation: Subtype: Link Rect: 226, 284, 264, 295 Annotation: Subtype: Link Rect: 319, 261, 357, 272 Annotation: Subtype: Link Rect: 317, 238, 355, 249 Annotation: Subtype: Link Rect: 361, 238, 397, 249 Annotation: Subtype: Link Rect: 457, 215, 495, 226 Annotation: Subtype: Link Rect: 501, 215, 537, 226 Annotation: Subtype: Link Rect: 280, 192, 318, 203 Annotation: Subtype: Link Rect: 138, 170, 175, 180 Annotation: Subtype: Link Rect: 182, 170, 218, 180 Annotation: Subtype: Link Rect: 95, 136, 133, 146 Annotation: Subtype: Link Rect: 139, 136, 175, 146 Annotation: Subtype: Link Rect: 520, 112, 557, 123 Annotation: Subtype: Link Rect: 59, 101, 95, 111 Annotation: Subtype: Link Rect: 295, 77, 333, 88 Annotation: Subtype: Link Rect: 339, 77, 375, 88 Page: Sequence: 28 Annotations: Annotation: Subtype: Link Rect: 59, 722, 96, 733 Annotation: Subtype: Link Rect: 397, 699, 435, 710 Annotation: Subtype: Link Rect: 104, 665, 141, 675 Annotation: Subtype: Link Rect: 520, 641, 557, 652 Annotation: Subtype: Link Rect: 59, 630, 95, 640 Annotation: Subtype: Link Rect: 162, 607, 200, 617 Annotation: Subtype: Link Rect: 206, 607, 242, 617 Annotation: Subtype: Link Rect: 326, 583, 364, 594 Annotation: Subtype: Link Rect: 370, 583, 406, 594 Annotation: Subtype: Link Rect: 267, 560, 305, 571 Annotation: Subtype: Link Rect: 311, 560, 347, 571 Annotation: Subtype: Link Rect: 386, 537, 424, 548 Annotation: Subtype: Link Rect: 59, 504, 96, 514 Annotation: Subtype: Link Rect: 251, 481, 288, 491 Annotation: Subtype: Link Rect: 156, 446, 194, 456 Annotation: Subtype: Link Rect: 95, 389, 133, 399 Annotation: Subtype: Link Rect: 295, 365, 332, 376 Annotation: Subtype: Link Rect: 389, 353, 426, 364 Annotation: Subtype: Link Rect: 59, 308, 96, 318 Annotation: Subtype: Link Rect: 102, 308, 138, 318 Annotation: Subtype: Link Rect: 430, 284, 468, 295 Annotation: Subtype: Link Rect: 474, 284, 510, 295 Annotation: Subtype: Link Rect: 330, 261, 368, 272 Annotation: Subtype: Link Rect: 374, 261, 410, 272 Annotation: Subtype: Link Rect: 193, 228, 230, 238 Annotation: Subtype: Link Rect: 236, 228, 272, 238 Annotation: Subtype: Link Rect: 59, 205, 96, 215 Annotation: Subtype: Link Rect: 95, 182, 133, 192 Annotation: Subtype: Link Rect: 210, 147, 247, 157 Annotation: Subtype: Link Rect: 253, 147, 289, 157 Annotation: Subtype: Link Rect: 381, 123, 419, 134 Annotation: Subtype: Link Rect: 425, 123, 461, 134 Annotation: Subtype: Link Rect: 59, 90, 96, 100 Page: Sequence: 29 Annotations: Annotation: Subtype: Link Rect: 95, 711, 133, 721 Annotation: Subtype: Link Rect: 139, 711, 175, 721 Annotation: Subtype: Link Rect: 229, 688, 266, 698 Annotation: Subtype: Link Rect: 273, 688, 309, 698 Annotation: Subtype: Link Rect: 135, 665, 173, 675 Annotation: Subtype: Link Rect: 354, 641, 392, 652 Annotation: Subtype: Link Rect: 398, 641, 434, 652 Annotation: Subtype: Link Rect: 370, 618, 407, 629 Annotation: Subtype: Link Rect: 248, 595, 285, 606 Annotation: Subtype: Link Rect: 120, 561, 157, 571 Annotation: Subtype: Link Rect: 144, 527, 182, 537 Annotation: Subtype: Link Rect: 299, 503, 336, 514 Annotation: Subtype: Link Rect: 342, 503, 379, 514 Annotation: Subtype: Link Rect: 520, 480, 557, 491 Annotation: Subtype: Link Rect: 59, 469, 95, 479 Annotation: Subtype: Link Rect: 394, 445, 432, 456 Annotation: Subtype: Link Rect: 438, 445, 474, 456 Annotation: Subtype: Link Rect: 500, 422, 537, 433 Annotation: Subtype: Link Rect: 90, 400, 128, 410 Annotation: Subtype: Link Rect: 265, 376, 303, 387 Annotation: Subtype: Link Rect: 499, 353, 537, 364 Annotation: Subtype: Link Rect: 104, 320, 141, 330 Annotation: Subtype: Link Rect: 158, 285, 195, 295 Annotation: Subtype: Link Rect: 325, 261, 362, 272 Annotation: Subtype: Link Rect: 420, 238, 457, 249 Annotation: Subtype: Link Rect: 464, 238, 500, 249 Annotation: Subtype: Link Rect: 520, 215, 557, 226 Annotation: Subtype: Link Rect: 59, 205, 95, 215 Annotation: Subtype: Link Rect: 460, 181, 498, 192 Annotation: Subtype: Link Rect: 400, 158, 437, 169 Annotation: Subtype: Link Rect: 444, 158, 480, 169 Annotation: Subtype: Link Rect: 444, 135, 481, 146 Annotation: Subtype: Link Rect: 487, 135, 523, 146 Annotation: Subtype: Link Rect: 59, 101, 96, 111 Annotation: Subtype: Link Rect: 102, 101, 138, 111 Annotation: Subtype: Link Rect: 227, 77, 265, 88 Checksum: 4f5b9ed3 Type: CRC32 Checksum: 4327c7e9b5482a93bb2618939a2e44f1 Type: MD5 Checksum: 821545654fe8f3ef6bd666e7fb60ded20d9d2405 Type: SHA-1 Checksum: 911cbf778cb447ace5ead578e2f78da16b96f6ea9d0cbf6ae67127e6b99b9425 Type: SHA-256