7f16a2402f14c33248ed078a906b0b82 269710.pdf de7b3b8c80f4b219c0b55b9973d497c5795a7b73 269710.pdf 129872c2e8e58a9a96839ac4055646278f3938ea0dfc5b32f765ee94b4120662 269710.pdf Title: Unraveling the Complexity of HDL Remodeling: On the Hunt to Restore HDL Quality Subject: Increasing evidence has cast doubt over the HDL-cholesterol hypothesis. The complexity of the HDL particle and its proven susceptibility to remodel has paved the way for intense molecular investigation. This state-of-the-art review discusses the molecular changes in HDL particles that help to explain the failure of large clinical trials intending to interfere with HDL metabolism, and details the chemical modifications and compositional changes in HDL-forming components, as well as miRNA cargo, that render HDL particles ineffective. Finally, the paper discusses the challenges that need to be overcome to shed a light of hope on HDL-targeted approaches. Keywords: HDL-cholesterol; HDL modifications; cardiovascular disease Author: Leonie Schoch, Lina Badimon and Gemma Vilahur Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jul 14 03:05:30 2021 CEST ModDate: Wed Jul 14 04:45:55 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2725489 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- NGLOQY+URWPalladioL-Ital Type 1 Custom yes yes no 10 0 XVQCAO+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 LAGLEO+URWPalladioL-Roma Type 1 Custom yes yes no 19 0 EBFBTV+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 27 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 49 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 53 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 57 0 UVLJSP+VnURWPalladioL Type 1 Custom yes yes no 84 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 95 0 UANSOM+URWPalladioL-BoldItal Type 1 Custom yes yes no 102 0 CKBPVA+EURM10 Type 1 Builtin yes yes no 125 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:15:00 CEST RepresentationInformation: 269710.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:04:43 CEST Size: 2725489 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 478 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: The HDL-C Hypothesis Revisited Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: HDL Particle Alterations: On the Lookout for What Makes HDL Particles Lose Their Protective Functions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: HDL Component Modifications Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Oxidation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Carbamylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Glycation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: HDL Component Replacements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: HDL miRNA Profile Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Genetic Alterations Affecting HDL Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Info: Title: Unraveling the Complexity of HDL Remodeling: On the Hunt to Restore HDL Quality Author: Leonie Schoch, Lina Badimon and Gemma Vilahur Subject: Increasing evidence has cast doubt over the HDL-cholesterol hypothesis. The complexity of the HDL particle and its proven susceptibility to remodel has paved the way for intense molecular investigation. This state-of-the-art review discusses the molecular changes in HDL particles that help to explain the failure of large clinical trials intending to interfere with HDL metabolism, and details the chemical modifications and compositional changes in HDL-forming components, as well as miRNA cargo, that render HDL particles ineffective. Finally, the paper discusses the challenges that need to be overcome to shed a light of hope on HDL-targeted approaches. Keywords: HDL-cholesterol; HDL modifications; cardiovascular disease Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jul 14 03:05:30 CEST 2021 ModDate: Wed Jul 14 04:45:55 CEST 2021 ID: 0x1e26c96a6109d393362bb9acacb9077c, 0x1e26c96a6109d393362bb9acacb9077c Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: LAGLEO+URWPalladioL-Roma FontSubset: true FirstChar: 1 LastChar: 252 FontDescriptor: FontName: LAGLEO+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: UVLJSP+VnURWPalladioL FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: UVLJSP+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: UANSOM+URWPalladioL-BoldItal FontSubset: true FirstChar: 97 LastChar: 119 FontDescriptor: FontName: UANSOM+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: NGLOQY+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: NGLOQY+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CKBPVA+EURM10 FontSubset: true FirstChar: 11 LastChar: 11 FontDescriptor: FontName: CKBPVA+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: XVQCAO+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: XVQCAO+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: MPUDFL+PazoMath FontSubset: true FirstChar: 68 LastChar: 68 FontDescriptor: FontName: MPUDFL+PazoMath Flags: Symbolic FontBBox: -40, -283, 878, 946 FontFile: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 35, 759, 198, 795 Annotation: Subtype: Link Rect: 515, 759, 560, 795 Annotation: Subtype: Link Rect: 114, 660, 125, 673 Annotation: Subtype: Link Rect: 213, 660, 224, 673 Annotation: Subtype: Link Rect: 114, 358, 154, 367 Annotation: Subtype: Link Rect: 35, 346, 155, 355 Annotation: Subtype: Link Rect: 35, 162, 97, 184 Annotation: Subtype: Link Rect: 153, 89, 154, 98 Annotation: Subtype: Link Rect: 35, 77, 147, 86 Annotation: Subtype: Link Rect: 302, 372, 309, 381 ActionDest: 109 Annotation: Subtype: Link Rect: 312, 372, 319, 381 ActionDest: 109 Annotation: Subtype: Link Rect: 289, 359, 296, 368 ActionDest: 109 Annotation: Subtype: Link Rect: 269, 322, 276, 331 ActionDest: 109 Annotation: Subtype: Link Rect: 463, 284, 470, 293 ActionDest: 109 Annotation: Subtype: Link Rect: 473, 284, 480, 293 ActionDest: 109 Annotation: Subtype: Link Rect: 360, 259, 372, 268 ActionDest: 109 Annotation: Subtype: Link Rect: 375, 259, 387, 268 ActionDest: 109 Annotation: Subtype: Link Rect: 512, 259, 524, 268 ActionDest: 109 Annotation: Subtype: Link Rect: 525, 259, 537, 268 ActionDest: 109 Annotation: Subtype: Link Rect: 298, 246, 310, 255 ActionDest: 109 Annotation: Subtype: Link Rect: 532, 247, 544, 255 ActionDest: 109 Annotation: Subtype: Link Rect: 544, 247, 556, 255 ActionDest: 109 Annotation: Subtype: Link Rect: 299, 234, 311, 243 ActionDest: 109 Annotation: Subtype: Link Rect: 311, 234, 323, 243 ActionDest: 109 Annotation: Subtype: Link Rect: 413, 231, 420, 243 ActionDest: 66 Annotation: Subtype: Link Rect: 501, 234, 512, 243 ActionDest: 112 Annotation: Subtype: Link Rect: 494, 209, 506, 218 ActionDest: 112 Annotation: Subtype: Link Rect: 507, 209, 519, 218 ActionDest: 112 Annotation: Subtype: Link Rect: 183, 196, 195, 205 ActionDest: 112 Annotation: Subtype: Link Rect: 196, 196, 208, 205 ActionDest: 112 Annotation: Subtype: Link Rect: 549, 146, 556, 155 ActionDest: 109 Annotation: Subtype: Link Rect: 123, 17, 290, 28 Annotation: Subtype: Link Rect: 387, 17, 558, 28 Annotation: Subtype: Link Rect: 35, 423, 87, 442 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 323, 365, 335, 374 ActionDest: 112 Annotation: Subtype: Link Rect: 487, 353, 499, 362 ActionDest: 112 Annotation: Subtype: Link Rect: 502, 353, 514, 362 ActionDest: 112 Annotation: Subtype: Link Rect: 401, 277, 413, 287 ActionDest: 112 Annotation: Subtype: Link Rect: 233, 252, 245, 261 ActionDest: 112 Annotation: Subtype: Link Rect: 318, 240, 330, 249 ActionDest: 112 Annotation: Subtype: Link Rect: 266, 177, 278, 186 ActionDest: 112 Annotation: Subtype: Link Rect: 279, 177, 291, 186 ActionDest: 112 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 273, 333, 284, 342 ActionDest: 112 Annotation: Subtype: Link Rect: 288, 333, 300, 342 ActionDest: 112 Annotation: Subtype: Link Rect: 403, 280, 410, 292 ActionDest: 75 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 207, 332, 219, 341 ActionDest: 112 Annotation: Subtype: Link Rect: 545, 332, 556, 341 ActionDest: 112 Annotation: Subtype: Link Rect: 298, 294, 310, 303 ActionDest: 112 Annotation: Subtype: Link Rect: 313, 295, 325, 303 ActionDest: 112 Annotation: Subtype: Link Rect: 195, 232, 207, 241 ActionDest: 112 Annotation: Subtype: Link Rect: 210, 232, 222, 241 ActionDest: 112 Annotation: Subtype: Link Rect: 390, 219, 402, 228 ActionDest: 112 Annotation: Subtype: Link Rect: 335, 194, 347, 203 ActionDest: 116 Annotation: Subtype: Link Rect: 392, 106, 404, 115 ActionDest: 116 Annotation: Subtype: Link Rect: 544, 106, 556, 115 ActionDest: 116 Annotation: Subtype: Link Rect: 326, 93, 338, 102 ActionDest: 116 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 351, 682, 363, 691 ActionDest: 116 Annotation: Subtype: Link Rect: 266, 644, 278, 653 ActionDest: 109 Annotation: Subtype: Link Rect: 544, 606, 556, 615 ActionDest: 116 Annotation: Subtype: Link Rect: 264, 543, 276, 553 ActionDest: 116 Annotation: Subtype: Link Rect: 399, 518, 411, 527 ActionDest: 116 Annotation: Subtype: Link Rect: 326, 493, 338, 502 ActionDest: 116 Annotation: Subtype: Link Rect: 176, 443, 188, 452 ActionDest: 116 Annotation: Subtype: Link Rect: 319, 418, 331, 427 ActionDest: 116 Annotation: Subtype: Link Rect: 324, 380, 336, 389 ActionDest: 116 Annotation: Subtype: Link Rect: 339, 380, 351, 389 ActionDest: 116 Annotation: Subtype: Link Rect: 215, 368, 227, 377 ActionDest: 116 Annotation: Subtype: Link Rect: 388, 355, 400, 364 ActionDest: 116 Annotation: Subtype: Link Rect: 208, 330, 220, 339 ActionDest: 116 Annotation: Subtype: Link Rect: 486, 317, 498, 327 ActionDest: 116 Annotation: Subtype: Link Rect: 290, 242, 301, 251 ActionDest: 116 Annotation: Subtype: Link Rect: 222, 204, 234, 213 ActionDest: 116 Annotation: Subtype: Link Rect: 233, 179, 245, 188 ActionDest: 116 Annotation: Subtype: Link Rect: 246, 167, 258, 176 ActionDest: 116 Annotation: Subtype: Link Rect: 207, 154, 219, 163 ActionDest: 116 Annotation: Subtype: Link Rect: 436, 154, 448, 163 ActionDest: 116 Annotation: Subtype: Link Rect: 195, 78, 207, 87 ActionDest: 116 Annotation: Subtype: Link Rect: 208, 78, 220, 87 ActionDest: 116 Annotation: Subtype: Link Rect: 451, 78, 463, 87 ActionDest: 116 Annotation: Subtype: Link Rect: 477, 66, 489, 75 ActionDest: 116 Annotation: Subtype: Link Rect: 490, 66, 502, 75 ActionDest: 119 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 219, 735, 231, 744 ActionDest: 119 Annotation: Subtype: Link Rect: 526, 735, 538, 744 ActionDest: 119 Annotation: Subtype: Link Rect: 327, 710, 339, 719 ActionDest: 119 Annotation: Subtype: Link Rect: 339, 710, 351, 719 ActionDest: 119 Annotation: Subtype: Link Rect: 544, 710, 556, 719 ActionDest: 119 Annotation: Subtype: Link Rect: 183, 622, 195, 631 ActionDest: 119 Annotation: Subtype: Link Rect: 531, 546, 543, 556 ActionDest: 119 Annotation: Subtype: Link Rect: 544, 546, 556, 556 ActionDest: 119 Annotation: Subtype: Link Rect: 462, 408, 474, 417 ActionDest: 119 Annotation: Subtype: Link Rect: 544, 371, 556, 380 ActionDest: 119 Annotation: Subtype: Link Rect: 198, 308, 210, 317 ActionDest: 119 Annotation: Subtype: Link Rect: 411, 283, 423, 292 ActionDest: 119 Annotation: Subtype: Link Rect: 231, 257, 243, 267 ActionDest: 119 Annotation: Subtype: Link Rect: 467, 257, 479, 267 ActionDest: 119 Annotation: Subtype: Link Rect: 277, 170, 289, 179 ActionDest: 119 Annotation: Subtype: Link Rect: 289, 170, 301, 179 ActionDest: 119 Annotation: Subtype: Link Rect: 430, 170, 442, 179 ActionDest: 119 Annotation: Subtype: Link Rect: 318, 157, 330, 166 ActionDest: 119 Annotation: Subtype: Link Rect: 531, 144, 543, 154 ActionDest: 119 Annotation: Subtype: Link Rect: 544, 144, 556, 154 ActionDest: 119 Annotation: Subtype: Link Rect: 210, 69, 222, 78 ActionDest: 119 Annotation: Subtype: Link Rect: 223, 69, 235, 78 ActionDest: 119 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 375, 722, 387, 731 ActionDest: 119 Annotation: Subtype: Link Rect: 387, 722, 399, 731 ActionDest: 119 Annotation: Subtype: Link Rect: 466, 622, 478, 631 ActionDest: 122 Annotation: Subtype: Link Rect: 374, 559, 386, 568 ActionDest: 122 Annotation: Subtype: Link Rect: 530, 534, 542, 543 ActionDest: 122 Annotation: Subtype: Link Rect: 518, 496, 530, 505 ActionDest: 122 Annotation: Subtype: Link Rect: 435, 446, 447, 455 ActionDest: 122 Annotation: Subtype: Link Rect: 544, 421, 556, 430 ActionDest: 122 Annotation: Subtype: Link Rect: 501, 320, 513, 330 ActionDest: 122 Annotation: Subtype: Link Rect: 242, 270, 254, 279 ActionDest: 122 Annotation: Subtype: Link Rect: 383, 245, 400, 254 ActionDest: 122 Annotation: Subtype: Link Rect: 297, 220, 314, 229 ActionDest: 122 Annotation: Subtype: Link Rect: 375, 195, 392, 204 ActionDest: 122 Annotation: Subtype: Link Rect: 393, 195, 410, 204 ActionDest: 122 Annotation: Subtype: Link Rect: 481, 170, 498, 179 ActionDest: 122 Annotation: Subtype: Link Rect: 360, 132, 377, 141 ActionDest: 122 Annotation: Subtype: Link Rect: 230, 79, 237, 91 ActionDest: 99 Annotation: Subtype: Link Rect: 337, 67, 344, 79 ActionDest: 99 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 301, 622, 318, 631 ActionDest: 122 Annotation: Subtype: Link Rect: 522, 597, 538, 606 ActionDest: 122 Annotation: Subtype: Link Rect: 539, 597, 556, 606 ActionDest: 122 Annotation: Subtype: Link Rect: 343, 572, 360, 581 ActionDest: 122 Annotation: Subtype: Link Rect: 524, 424, 539, 432 ActionDest: 122 Annotation: Subtype: Link Rect: 524, 314, 539, 323 ActionDest: 122 Annotation: Subtype: Link Rect: 524, 243, 539, 252 ActionDest: 122 Annotation: Subtype: Link Rect: 524, 194, 539, 202 ActionDest: 122 Annotation: Subtype: Link Rect: 201, 100, 208, 112 ActionDest: 75 Annotation: Subtype: Link Rect: 226, 75, 233, 87 ActionDest: 106 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 508, 666, 523, 674 ActionDest: 122 Annotation: Subtype: Link Rect: 526, 666, 541, 674 ActionDest: 122 Annotation: Subtype: Link Rect: 508, 578, 523, 587 ActionDest: 122 Annotation: Subtype: Link Rect: 526, 579, 541, 587 ActionDest: 129 Annotation: Subtype: Link Rect: 508, 496, 523, 505 ActionDest: 129 Annotation: Subtype: Link Rect: 526, 496, 541, 505 ActionDest: 129 Annotation: Subtype: Link Rect: 502, 458, 513, 466 ActionDest: 112 Annotation: Subtype: Link Rect: 513, 458, 529, 466 ActionDest: 129 Annotation: Subtype: Link Rect: 531, 458, 547, 466 ActionDest: 129 Annotation: Subtype: Link Rect: 500, 414, 515, 422 ActionDest: 122 Annotation: Subtype: Link Rect: 516, 414, 531, 422 ActionDest: 129 Annotation: Subtype: Link Rect: 534, 414, 549, 422 ActionDest: 129 Annotation: Subtype: Link Rect: 508, 354, 523, 362 ActionDest: 129 Annotation: Subtype: Link Rect: 526, 354, 541, 362 ActionDest: 129 Annotation: Subtype: Link Rect: 508, 299, 523, 307 ActionDest: 129 Annotation: Subtype: Link Rect: 526, 299, 541, 307 ActionDest: 129 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 276, 478, 314, 489 Annotation: Subtype: Link Rect: 334, 455, 372, 466 Annotation: Subtype: Link Rect: 378, 455, 414, 466 Annotation: Subtype: Link Rect: 522, 443, 557, 454 Annotation: Subtype: Link Rect: 183, 409, 220, 419 Annotation: Subtype: Link Rect: 227, 409, 263, 419 Annotation: Subtype: Link Rect: 276, 386, 313, 396 Annotation: Subtype: Link Rect: 59, 352, 97, 362 Annotation: Subtype: Link Rect: 103, 352, 139, 362 Annotation: Subtype: Link Rect: 493, 339, 530, 350 Annotation: Subtype: Link Rect: 299, 316, 337, 327 Annotation: Subtype: Link Rect: 279, 271, 317, 281 Annotation: Subtype: Link Rect: 285, 247, 322, 258 Annotation: Subtype: Link Rect: 329, 247, 365, 258 Annotation: Subtype: Link Rect: 113, 225, 151, 235 Annotation: Subtype: Link Rect: 59, 179, 97, 189 Annotation: Subtype: Link Rect: 103, 179, 139, 189 Annotation: Subtype: Link Rect: 198, 156, 236, 166 Annotation: Subtype: Link Rect: 242, 156, 278, 166 Annotation: Subtype: Link Rect: 158, 122, 196, 132 Annotation: Subtype: Link Rect: 407, 98, 444, 109 Annotation: Subtype: Link Rect: 518, 86, 554, 97 Annotation: Subtype: Link Rect: 95, 64, 132, 74 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 292, 722, 329, 732 Annotation: Subtype: Link Rect: 275, 698, 312, 709 Annotation: Subtype: Link Rect: 365, 663, 403, 674 Annotation: Subtype: Link Rect: 175, 630, 212, 640 Annotation: Subtype: Link Rect: 211, 594, 248, 605 Annotation: Subtype: Link Rect: 113, 561, 151, 571 Annotation: Subtype: Link Rect: 59, 526, 97, 536 Annotation: Subtype: Link Rect: 103, 526, 139, 536 Annotation: Subtype: Link Rect: 504, 502, 539, 513 Annotation: Subtype: Link Rect: 104, 469, 141, 479 Annotation: Subtype: Link Rect: 522, 456, 557, 467 Annotation: Subtype: Link Rect: 146, 422, 184, 433 Annotation: Subtype: Link Rect: 190, 422, 226, 433 Annotation: Subtype: Link Rect: 487, 399, 524, 410 Annotation: Subtype: Link Rect: 519, 376, 557, 387 Annotation: Subtype: Link Rect: 82, 342, 119, 352 Annotation: Subtype: Link Rect: 486, 330, 524, 341 Annotation: Subtype: Link Rect: 59, 285, 97, 295 Annotation: Subtype: Link Rect: 103, 285, 139, 295 Annotation: Subtype: Link Rect: 229, 249, 266, 260 Annotation: Subtype: Link Rect: 272, 249, 308, 260 Annotation: Subtype: Link Rect: 513, 238, 551, 249 Annotation: Subtype: Link Rect: 516, 226, 552, 237 Annotation: Subtype: Link Rect: 59, 204, 97, 214 Annotation: Subtype: Link Rect: 103, 204, 139, 214 Annotation: Subtype: Link Rect: 349, 180, 387, 191 Annotation: Subtype: Link Rect: 261, 157, 299, 168 Annotation: Subtype: Link Rect: 95, 135, 132, 145 Annotation: Subtype: Link Rect: 163, 100, 201, 111 Annotation: Subtype: Link Rect: 77, 66, 115, 76 Annotation: Subtype: Link Rect: 121, 66, 157, 76 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 59, 722, 97, 732 Annotation: Subtype: Link Rect: 103, 722, 139, 732 Annotation: Subtype: Link Rect: 59, 699, 97, 709 Annotation: Subtype: Link Rect: 103, 699, 139, 709 Annotation: Subtype: Link Rect: 154, 676, 191, 686 Annotation: Subtype: Link Rect: 59, 653, 97, 663 Annotation: Subtype: Link Rect: 103, 653, 139, 663 Annotation: Subtype: Link Rect: 59, 618, 97, 628 Annotation: Subtype: Link Rect: 103, 618, 139, 628 Annotation: Subtype: Link Rect: 493, 594, 531, 605 Annotation: Subtype: Link Rect: 211, 572, 248, 582 Annotation: Subtype: Link Rect: 254, 572, 290, 582 Annotation: Subtype: Link Rect: 393, 537, 431, 548 Annotation: Subtype: Link Rect: 324, 514, 362, 525 Annotation: Subtype: Link Rect: 140, 480, 178, 490 Annotation: Subtype: Link Rect: 184, 480, 220, 490 Annotation: Subtype: Link Rect: 468, 456, 506, 467 Annotation: Subtype: Link Rect: 289, 422, 326, 433 Annotation: Subtype: Link Rect: 457, 387, 494, 398 Annotation: Subtype: Link Rect: 477, 364, 514, 375 Annotation: Subtype: Link Rect: 104, 331, 142, 341 Annotation: Subtype: Link Rect: 402, 295, 439, 306 Annotation: Subtype: Link Rect: 395, 272, 433, 283 Annotation: Subtype: Link Rect: 520, 249, 557, 260 Annotation: Subtype: Link Rect: 444, 215, 482, 226 Annotation: Subtype: Link Rect: 488, 215, 524, 226 Annotation: Subtype: Link Rect: 59, 181, 97, 191 Annotation: Subtype: Link Rect: 191, 146, 228, 157 Annotation: Subtype: Link Rect: 59, 123, 97, 134 Annotation: Subtype: Link Rect: 103, 123, 139, 134 Annotation: Subtype: Link Rect: 59, 89, 97, 99 Annotation: Subtype: Link Rect: 103, 89, 139, 99 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 207, 709, 245, 720 Annotation: Subtype: Link Rect: 332, 686, 370, 697 Annotation: Subtype: Link Rect: 376, 686, 412, 697 Annotation: Subtype: Link Rect: 59, 653, 97, 663 Annotation: Subtype: Link Rect: 103, 653, 139, 663 Annotation: Subtype: Link Rect: 515, 629, 553, 640 Annotation: Subtype: Link Rect: 417, 594, 455, 605 Annotation: Subtype: Link Rect: 136, 561, 173, 571 Annotation: Subtype: Link Rect: 179, 561, 216, 571 Annotation: Subtype: Link Rect: 173, 526, 210, 536 Annotation: Subtype: Link Rect: 522, 514, 557, 525 Annotation: Subtype: Link Rect: 427, 479, 465, 490 Annotation: Subtype: Link Rect: 113, 457, 151, 467 Annotation: Subtype: Link Rect: 504, 433, 541, 444 Annotation: Subtype: Link Rect: 148, 399, 186, 410 Annotation: Subtype: Link Rect: 473, 376, 510, 387 Annotation: Subtype: Link Rect: 444, 353, 481, 364 Annotation: Subtype: Link Rect: 389, 318, 426, 329 Annotation: Subtype: Link Rect: 434, 272, 472, 283 Annotation: Subtype: Link Rect: 492, 249, 529, 260 Annotation: Subtype: Link Rect: 104, 227, 141, 237 Annotation: Subtype: Link Rect: 104, 204, 142, 214 Annotation: Subtype: Link Rect: 520, 180, 557, 191 Annotation: Subtype: Link Rect: 59, 169, 95, 180 Annotation: Subtype: Link Rect: 59, 135, 97, 145 Annotation: Subtype: Link Rect: 103, 135, 139, 145 Annotation: Subtype: Link Rect: 206, 112, 243, 122 Annotation: Subtype: Link Rect: 441, 77, 479, 88 Annotation: Subtype: Link Rect: 485, 77, 521, 88 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 218, 710, 255, 720 Annotation: Subtype: Link Rect: 131, 676, 169, 686 Annotation: Subtype: Link Rect: 175, 676, 211, 686 Annotation: Subtype: Link Rect: 283, 652, 321, 663 Annotation: Subtype: Link Rect: 327, 652, 363, 663 Annotation: Subtype: Link Rect: 478, 629, 515, 640 Annotation: Subtype: Link Rect: 521, 629, 557, 640 Annotation: Subtype: Link Rect: 507, 571, 542, 582 Annotation: Subtype: Link Rect: 440, 537, 478, 548 Annotation: Subtype: Link Rect: 262, 503, 300, 513 Annotation: Subtype: Link Rect: 306, 503, 342, 513 Annotation: Subtype: Link Rect: 198, 468, 236, 479 Annotation: Subtype: Link Rect: 222, 445, 260, 456 Annotation: Subtype: Link Rect: 95, 423, 133, 433 Annotation: Subtype: Link Rect: 230, 388, 267, 398 Annotation: Subtype: Link Rect: 482, 364, 518, 375 Annotation: Subtype: Link Rect: 377, 330, 414, 341 Annotation: Subtype: Link Rect: 423, 307, 461, 318 Annotation: Subtype: Link Rect: 467, 307, 503, 318 Annotation: Subtype: Link Rect: 104, 273, 141, 283 Annotation: Subtype: Link Rect: 148, 273, 184, 283 Annotation: Subtype: Link Rect: 362, 238, 399, 249 Annotation: Subtype: Link Rect: 405, 238, 441, 249 Annotation: Subtype: Link Rect: 235, 203, 272, 214 Annotation: Subtype: Link Rect: 216, 192, 443, 204 Annotation: Subtype: Link Rect: 59, 169, 97, 180 Annotation: Subtype: Link Rect: 103, 169, 139, 180 Annotation: Subtype: Link Rect: 483, 146, 519, 157 Annotation: Subtype: Link Rect: 59, 123, 97, 134 Annotation: Subtype: Link Rect: 103, 123, 139, 134 Annotation: Subtype: Link Rect: 100, 89, 137, 99 Annotation: Subtype: Link Rect: 143, 89, 179, 99 Annotation: Subtype: Link Rect: 424, 77, 461, 88 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 216, 710, 253, 720 Annotation: Subtype: Link Rect: 131, 676, 169, 686 Annotation: Subtype: Link Rect: 394, 652, 431, 663 Annotation: Subtype: Link Rect: 460, 617, 497, 628 Annotation: Subtype: Link Rect: 523, 606, 557, 617 Annotation: Subtype: Link Rect: 292, 571, 329, 582 Annotation: Subtype: Link Rect: 336, 571, 372, 582 Annotation: Subtype: Link Rect: 118, 538, 155, 548 Annotation: Subtype: Link Rect: 297, 502, 334, 513 Annotation: Subtype: Link Rect: 341, 502, 377, 513 Annotation: Subtype: Link Rect: 136, 480, 173, 490 Annotation: Subtype: Link Rect: 179, 480, 216, 490 Annotation: Subtype: Link Rect: 100, 446, 137, 456 Annotation: Subtype: Link Rect: 234, 411, 271, 421 Annotation: Subtype: Link Rect: 278, 411, 314, 421 Annotation: Subtype: Link Rect: 313, 376, 351, 387 Annotation: Subtype: Link Rect: 357, 376, 393, 387 Annotation: Subtype: Link Rect: 389, 353, 427, 364 Annotation: Subtype: Link Rect: 433, 353, 469, 364 Annotation: Subtype: Link Rect: 360, 318, 397, 329 Annotation: Subtype: Link Rect: 403, 318, 439, 329 Annotation: Subtype: Link Rect: 519, 295, 555, 306 Annotation: Subtype: Link Rect: 393, 272, 431, 283 Annotation: Subtype: Link Rect: 284, 249, 321, 260 Annotation: Subtype: Link Rect: 327, 249, 363, 260 Annotation: Subtype: Link Rect: 259, 215, 296, 226 Annotation: Subtype: Link Rect: 314, 192, 352, 203 Annotation: Subtype: Link Rect: 298, 169, 336, 180 Annotation: Subtype: Link Rect: 342, 169, 378, 180 Annotation: Subtype: Link Rect: 478, 146, 515, 157 Annotation: Subtype: Link Rect: 521, 146, 557, 157 Annotation: Subtype: Link Rect: 95, 112, 133, 122 Annotation: Subtype: Link Rect: 139, 112, 175, 122 Checksum: aa935107 Type: CRC32 Checksum: 7f16a2402f14c33248ed078a906b0b82 Type: MD5 Checksum: de7b3b8c80f4b219c0b55b9973d497c5795a7b73 Type: SHA-1