be7932a547c07a73b6bb796683a8d625 pmc_34943238.pdf 090c2e3bc85ed3bdf1f56dfcf04492cbef61a0fc pmc_34943238.pdf 6d267d09baff2c95390b3b767b14f0917701bf5b2fa272b4db05e1a96ade6702 pmc_34943238.pdf Title: Genomic Analysis of 18th-Century Kazakh Individuals and Their Oral Microbiome Subject: The Asian Central Steppe, consisting of current-day Kazakhstan and Russia, has acted as a highway for major migrations throughout history. Therefore, describing the genetic composition of past populations in Central Asia holds value to understanding human mobility in this pivotal region. In this study, we analyse paleogenomic data generated from five humans from Kuygenzhar, Kazakhstan. These individuals date to the early to mid-18th century, shortly after the Kazakh Khanate was founded, a union of nomadic tribes of Mongol Golden Horde and Turkic origins. Genomic analysis identifies that these individuals are admixed with varying proportions of East Asian ancestry, indicating a recent admixture event from East Asia. The high amounts of DNA from the anaerobic Gram-negative bacteria Tannerella forsythia, a periodontal pathogen, recovered from their teeth suggest they may have suffered from periodontitis disease. Genomic analysis of this bacterium identified recently evolved virulence and glycosylation genes including the presence of antibiotic resistance genes predating the antibiotic era. This study provides an integrated analysis of individuals with a diet mostly based on meat (mainly horse and lamb), milk, and dairy products and their oral microbiome. Keywords: paleogenomics; ancient pathogens; Central Asian steppe; red complex; bacteria Author: Anna E. White, Toni de-Dios, Pablo Carrión, Gian Luca Bonora, Laia Llovera, Elisabetta Cilli, Esther Lizano, Maral K. Khabdulina, Daniyar T. Tleugabulov, Iñigo Olalde, Tomàs Marquès-Bonet, François Balloux, Davide Pettener, Lucy van Dorp, Donata Luiselli and Carles Lalueza-Fox Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Dec 15 12:19:52 2021 CET ModDate: Thu Dec 23 05:27:17 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3946905 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MJPLRG+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 KORLVE+VnURWPalladioL Type 1 Custom yes yes no 15 0 IHBZQZ+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 GRZJPL+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 ZJCOKS+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 GLCFZC+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 QUJCUM+CMSY10 Type 1 Builtin yes yes no 81 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 85 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-22 02:27:50 CET RepresentationInformation: pmc_34943238.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-01-10 07:59:32 CET Size: 3946905 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 516 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Ancient DNA Extraction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Processing of Sequencing Data and Mapping to the Human Genome Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Assessing the Authenticity of the Human Genomic Data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Assessing the Genetic Sex and Degree of Contamination Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Mitochondrial DNA and Y-Chromosome Haplogroup Determination Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Kinship Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Analysing Population Structure via Clustering Algorithms Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Ancestry Modelling Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Processing of Sequencing Data and Mapping of Ancient Microbes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Assessing the Authenticity of the Ancient Microbial DNA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Phylogenetic Analysis of T. forsythia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Phylogenetic Dataset Filtering Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Tip Calibrated Dating Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Phylogenetic Analysis of T. denticola and P. gingivalis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: T. forsythia Pan-Genome Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Children: Item: Title: Human DNA Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Children: Item: Title: Assessing aDNA Reliability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Uniparental Markers and Kinship Relationships Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Human Genetic Data Exploration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: f-Statistics Ancestry Modelling Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Microbiome Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Children: Item: Title: Red Complex Bacteria Detection and Authentication Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Tannerella Forsythia Phylogeny and Clade Dating Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Presence of Virulence or Lifestyle-Related Tannerella Genes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: T. denticola and P. gingivalis Trees Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: Patents Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Info: Title: Genomic Analysis of 18th-Century Kazakh Individuals and Their Oral Microbiome Author: Anna E. White, Toni de-Dios, Pablo Carrión, Gian Luca Bonora, Laia Llovera, Elisabetta Cilli, Esther Lizano, Maral K. Khabdulina, Daniyar T. Tleugabulov, Iñigo Olalde, Tomàs Marquès-Bonet, François Balloux, Davide Pettener, Lucy van Dorp, Donata Luiselli and Carles Lalueza-Fox Subject: The Asian Central Steppe, consisting of current-day Kazakhstan and Russia, has acted as a highway for major migrations throughout history. Therefore, describing the genetic composition of past populations in Central Asia holds value to understanding human mobility in this pivotal region. In this study, we analyse paleogenomic data generated from five humans from Kuygenzhar, Kazakhstan. These individuals date to the early to mid-18th century, shortly after the Kazakh Khanate was founded, a union of nomadic tribes of Mongol Golden Horde and Turkic origins. Genomic analysis identifies that these individuals are admixed with varying proportions of East Asian ancestry, indicating a recent admixture event from East Asia. The high amounts of DNA from the anaerobic Gram-negative bacteria Tannerella forsythia, a periodontal pathogen, recovered from their teeth suggest they may have suffered from periodontitis disease. Genomic analysis of this bacterium identified recently evolved virulence and glycosylation genes including the presence of antibiotic resistance genes predating the antibiotic era. This study provides an integrated analysis of individuals with a diet mostly based on meat (mainly horse and lamb), milk, and dairy products and their oral microbiome. Keywords: paleogenomics; ancient pathogens; Central Asian steppe; red complex; bacteria Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Dec 15 12:19:52 CET 2021 ModDate: Thu Dec 23 05:27:17 CET 2021 ID: 0x4603570bd54fb3383d841d4eaea5cf23, 0x4603570bd54fb3383d841d4eaea5cf23 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: QUJCUM+CMSY10 FontSubset: true FirstChar: 1 LastChar: 48 FontDescriptor: FontName: QUJCUM+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: IHBZQZ+URWPalladioL-Ital FontSubset: true FirstChar: 44 LastChar: 121 FontDescriptor: FontName: IHBZQZ+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: OVNEXW+EURM10 FontSubset: true FirstChar: 22 LastChar: 22 FontDescriptor: FontName: OVNEXW+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: GRZJPL+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 241 FontDescriptor: FontName: GRZJPL+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: MJPLRG+VnURWPalladioL-Bold FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: MJPLRG+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ZJCOKS+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: ZJCOKS+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: KORLVE+VnURWPalladioL FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: KORLVE+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 35, 759, 151, 795 Annotation: Subtype: Link Rect: 515, 759, 560, 795 Annotation: Subtype: Link Rect: 114, 663, 125, 675 Annotation: Subtype: Link Rect: 207, 663, 218, 675 Annotation: Subtype: Link Rect: 539, 663, 550, 675 Annotation: Subtype: Link Rect: 110, 649, 121, 663 Annotation: Subtype: Link Rect: 388, 636, 400, 650 Annotation: Subtype: Link Rect: 519, 636, 530, 650 Annotation: Subtype: Link Rect: 147, 358, 154, 367 Annotation: Subtype: Link Rect: 35, 346, 154, 355 Annotation: Subtype: Link Rect: 35, 334, 88, 343 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: 113, 17, 264, 28 Annotation: Subtype: Link Rect: 408, 17, 558, 28 Annotation: Subtype: Link Rect: 35, 446, 87, 465 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 539, 583, 546, 592 ActionDest: 147 Annotation: Subtype: Link Rect: 549, 583, 556, 592 ActionDest: 147 Annotation: Subtype: Link Rect: 472, 558, 479, 567 ActionDest: 147 Annotation: Subtype: Link Rect: 479, 558, 486, 567 ActionDest: 147 Annotation: Subtype: Link Rect: 489, 558, 496, 567 ActionDest: 147 Annotation: Subtype: Link Rect: 378, 533, 385, 542 ActionDest: 147 Annotation: Subtype: Link Rect: 480, 495, 487, 504 ActionDest: 147 Annotation: Subtype: Link Rect: 487, 495, 494, 504 ActionDest: 147 Annotation: Subtype: Link Rect: 497, 495, 509, 504 ActionDest: 147 Annotation: Subtype: Link Rect: 505, 432, 517, 441 ActionDest: 147 Annotation: Subtype: Link Rect: 368, 294, 380, 303 ActionDest: 147 Annotation: Subtype: Link Rect: 234, 219, 246, 228 ActionDest: 147 Annotation: Subtype: Link Rect: 247, 219, 259, 228 ActionDest: 147 Annotation: Subtype: Link Rect: 367, 181, 379, 190 ActionDest: 147 Annotation: Subtype: Link Rect: 379, 181, 391, 190 ActionDest: 147 Annotation: Subtype: Link Rect: 209, 169, 221, 178 ActionDest: 147 Annotation: Subtype: Link Rect: 222, 169, 234, 178 ActionDest: 147 Annotation: Subtype: Link Rect: 528, 169, 540, 178 ActionDest: 147 Annotation: Subtype: Link Rect: 543, 169, 555, 178 ActionDest: 150 Annotation: Subtype: Link Rect: 492, 93, 504, 102 ActionDest: 150 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 494, 656, 506, 665 ActionDest: 150 Annotation: Subtype: Link Rect: 336, 518, 348, 527 ActionDest: 150 Annotation: Subtype: Link Rect: 544, 429, 556, 438 ActionDest: 150 Annotation: Subtype: Link Rect: 402, 379, 414, 388 ActionDest: 150 Annotation: Subtype: Link Rect: 453, 354, 464, 363 ActionDest: 150 Annotation: Subtype: Link Rect: 474, 341, 486, 351 ActionDest: 150 Annotation: Subtype: Link Rect: 361, 329, 373, 338 ActionDest: 150 Annotation: Subtype: Link Rect: 314, 316, 326, 325 ActionDest: 150 Annotation: Subtype: Link Rect: 492, 316, 504, 325 ActionDest: 150 Annotation: Subtype: Link Rect: 483, 241, 495, 250 ActionDest: 150 Annotation: Subtype: Link Rect: 495, 241, 507, 250 ActionDest: 150 Annotation: Subtype: Link Rect: 418, 228, 430, 237 ActionDest: 150 Annotation: Subtype: Link Rect: 430, 228, 442, 237 ActionDest: 150 Annotation: Subtype: Link Rect: 448, 216, 460, 225 ActionDest: 150 Annotation: Subtype: Link Rect: 461, 216, 473, 225 ActionDest: 150 Annotation: Subtype: Link Rect: 344, 165, 356, 174 ActionDest: 150 Annotation: Subtype: Link Rect: 497, 153, 509, 162 ActionDest: 150 Annotation: Subtype: Link Rect: 198, 140, 210, 149 ActionDest: 150 Annotation: Subtype: Link Rect: 544, 102, 556, 111 ActionDest: 150 Annotation: Subtype: Link Rect: 400, 77, 412, 86 ActionDest: 150 Annotation: Subtype: Link Rect: 544, 77, 556, 86 ActionDest: 150 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 399, 732, 502, 744 Annotation: Subtype: Link Rect: 420, 672, 432, 681 ActionDest: 150 Annotation: Subtype: Link Rect: 176, 581, 356, 593 Annotation: Subtype: Link Rect: 485, 558, 497, 567 ActionDest: 150 Annotation: Subtype: Link Rect: 407, 483, 419, 492 ActionDest: 150 Annotation: Subtype: Link Rect: 419, 483, 431, 492 ActionDest: 150 Annotation: Subtype: Link Rect: 524, 458, 531, 467 ActionDest: 147 Annotation: Subtype: Link Rect: 531, 458, 543, 467 ActionDest: 150 Annotation: Subtype: Link Rect: 544, 458, 556, 467 ActionDest: 153 Annotation: Subtype: Link Rect: 324, 420, 336, 429 ActionDest: 153 Annotation: Subtype: Link Rect: 290, 383, 302, 392 ActionDest: 153 Annotation: Subtype: Link Rect: 319, 345, 331, 354 ActionDest: 153 Annotation: Subtype: Link Rect: 244, 294, 256, 304 ActionDest: 153 Annotation: Subtype: Link Rect: 239, 282, 251, 291 ActionDest: 153 Annotation: Subtype: Link Rect: 544, 282, 556, 291 ActionDest: 153 Annotation: Subtype: Link Rect: 311, 242, 560, 254 Annotation: Subtype: Link Rect: 166, 229, 517, 241 Annotation: Subtype: Link Rect: 272, 106, 279, 115 ActionDest: 147 Annotation: Subtype: Link Rect: 279, 106, 291, 115 ActionDest: 153 Annotation: Subtype: Link Rect: 261, 81, 268, 90 ActionDest: 147 Annotation: Subtype: Link Rect: 268, 81, 275, 90 ActionDest: 147 Annotation: Subtype: Link Rect: 275, 81, 286, 90 ActionDest: 147 Annotation: Subtype: Link Rect: 287, 81, 298, 90 ActionDest: 153 Annotation: Subtype: Link Rect: 301, 81, 312, 90 ActionDest: 153 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 209, 672, 221, 681 ActionDest: 153 Annotation: Subtype: Link Rect: 221, 672, 233, 681 ActionDest: 153 Annotation: Subtype: Link Rect: 251, 621, 263, 631 ActionDest: 147 Annotation: Subtype: Link Rect: 379, 571, 391, 580 ActionDest: 150 Annotation: Subtype: Link Rect: 300, 534, 312, 543 ActionDest: 153 Annotation: Subtype: Link Rect: 229, 521, 241, 530 ActionDest: 150 Annotation: Subtype: Link Rect: 493, 509, 505, 518 ActionDest: 150 Annotation: Subtype: Link Rect: 267, 496, 279, 505 ActionDest: 153 Annotation: Subtype: Link Rect: 283, 471, 295, 480 ActionDest: 153 Annotation: Subtype: Link Rect: 508, 358, 520, 367 ActionDest: 150 Annotation: Subtype: Link Rect: 521, 358, 533, 367 ActionDest: 150 Annotation: Subtype: Link Rect: 488, 332, 500, 342 ActionDest: 150 Annotation: Subtype: Link Rect: 454, 307, 466, 316 ActionDest: 153 Annotation: Subtype: Link Rect: 382, 131, 394, 140 ActionDest: 150 Annotation: Subtype: Link Rect: 439, 119, 451, 128 ActionDest: 153 Annotation: Subtype: Link Rect: 343, 78, 558, 90 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 268, 672, 280, 681 ActionDest: 153 Annotation: Subtype: Link Rect: 332, 672, 344, 681 ActionDest: 153 Annotation: Subtype: Link Rect: 259, 609, 271, 618 ActionDest: 153 Annotation: Subtype: Link Rect: 245, 596, 257, 605 ActionDest: 153 Annotation: Subtype: Link Rect: 477, 508, 489, 518 ActionDest: 153 Annotation: Subtype: Link Rect: 478, 496, 489, 505 ActionDest: 153 Annotation: Subtype: Link Rect: 222, 408, 234, 417 ActionDest: 153 Annotation: Subtype: Link Rect: 401, 244, 413, 253 ActionDest: 153 Annotation: Subtype: Link Rect: 343, 207, 355, 216 ActionDest: 153 Annotation: Subtype: Link Rect: 350, 144, 361, 153 ActionDest: 147 Annotation: Subtype: Link Rect: 362, 144, 374, 153 ActionDest: 153 Annotation: Subtype: Link Rect: 374, 144, 386, 153 ActionDest: 153 Annotation: Subtype: Link Rect: 378, 118, 390, 128 ActionDest: 153 Annotation: Subtype: Link Rect: 468, 106, 480, 115 ActionDest: 150 Annotation: Subtype: Link Rect: 304, 93, 316, 102 ActionDest: 153 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 277, 652, 284, 664 ActionDest: 98 Annotation: Subtype: Link Rect: 545, 315, 556, 324 ActionDest: 156 Annotation: Subtype: Link Rect: 455, 290, 467, 298 ActionDest: 156 Annotation: Subtype: Link Rect: 328, 239, 340, 248 ActionDest: 156 Annotation: Subtype: Link Rect: 347, 227, 359, 236 ActionDest: 156 Annotation: Subtype: Link Rect: 531, 189, 543, 198 ActionDest: 156 Annotation: Subtype: Link Rect: 544, 189, 556, 198 ActionDest: 156 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 426, 704, 433, 716 ActionDest: 101 Annotation: Subtype: Link Rect: 332, 144, 339, 156 ActionDest: 101 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 251, 697, 263, 706 ActionDest: 153 Annotation: Subtype: Link Rect: 191, 559, 198, 568 ActionDest: 147 Annotation: Subtype: Link Rect: 198, 559, 205, 568 ActionDest: 147 Annotation: Subtype: Link Rect: 206, 559, 218, 568 ActionDest: 147 Annotation: Subtype: Link Rect: 218, 559, 230, 568 ActionDest: 153 Annotation: Subtype: Link Rect: 233, 559, 245, 568 ActionDest: 153 Annotation: Subtype: Link Rect: 348, 496, 360, 505 ActionDest: 147 Annotation: Subtype: Link Rect: 366, 483, 373, 492 ActionDest: 147 Annotation: Subtype: Link Rect: 373, 483, 385, 492 ActionDest: 153 Annotation: Subtype: Link Rect: 351, 279, 358, 291 ActionDest: 107 Annotation: Subtype: Link Rect: 319, 229, 326, 241 ActionDest: 110 Annotation: Subtype: Link Rect: 498, 203, 505, 215 ActionDest: 116 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 214, 314, 221, 326 ActionDest: 107 Annotation: Subtype: Link Rect: 257, 314, 264, 326 ActionDest: 110 Annotation: Subtype: Link Rect: 270, 277, 277, 289 ActionDest: 110 Annotation: Subtype: Link Rect: 267, 164, 274, 176 ActionDest: 116 Annotation: Subtype: Link Rect: 502, 154, 514, 163 ActionDest: 147 Annotation: Subtype: Link Rect: 514, 154, 526, 163 ActionDest: 153 Annotation: Subtype: Link Rect: 366, 129, 378, 138 ActionDest: 156 Annotation: Subtype: Link Rect: 379, 129, 391, 138 ActionDest: 156 Annotation: Subtype: Link Rect: 235, 116, 247, 125 ActionDest: 147 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 553, 197, 560, 209 ActionDest: 123 Annotation: Subtype: Link Rect: 363, 149, 374, 159 ActionDest: 147 Page: Sequence: 12 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 492, 694, 499, 708 ActionDest: 129 Annotation: Subtype: Link Rect: 456, 669, 463, 681 ActionDest: 129 Annotation: Subtype: Link Rect: 467, 302, 479, 311 ActionDest: 153 Annotation: Subtype: Link Rect: 544, 251, 556, 261 ActionDest: 153 Annotation: Subtype: Link Rect: 265, 113, 277, 123 ActionDest: 156 Annotation: Subtype: Link Rect: 278, 113, 290, 123 ActionDest: 156 Annotation: Subtype: Link Rect: 502, 101, 514, 110 ActionDest: 156 Annotation: Subtype: Link Rect: 515, 101, 527, 110 ActionDest: 156 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 259, 722, 271, 731 ActionDest: 156 Annotation: Subtype: Link Rect: 447, 672, 459, 681 ActionDest: 147 Annotation: Subtype: Link Rect: 459, 672, 471, 681 ActionDest: 153 Annotation: Subtype: Link Rect: 289, 647, 301, 656 ActionDest: 147 Annotation: Subtype: Link Rect: 302, 647, 314, 656 ActionDest: 153 Annotation: Subtype: Link Rect: 343, 559, 355, 568 ActionDest: 153 Annotation: Subtype: Link Rect: 449, 408, 456, 417 ActionDest: 147 Annotation: Subtype: Link Rect: 456, 408, 463, 417 ActionDest: 147 Annotation: Subtype: Link Rect: 464, 408, 471, 417 ActionDest: 147 Annotation: Subtype: Link Rect: 419, 383, 431, 392 ActionDest: 147 Annotation: Subtype: Link Rect: 431, 383, 443, 392 ActionDest: 150 Annotation: Subtype: Link Rect: 444, 383, 456, 392 ActionDest: 153 Annotation: Subtype: Link Rect: 456, 383, 468, 392 ActionDest: 156 Annotation: Subtype: Link Rect: 258, 292, 265, 304 ActionDest: 110 Annotation: Subtype: Link Rect: 236, 232, 248, 241 ActionDest: 147 Annotation: Subtype: Link Rect: 286, 229, 293, 241 ActionDest: 101 Annotation: Subtype: Link Rect: 324, 194, 331, 203 ActionDest: 147 Annotation: Subtype: Link Rect: 331, 195, 343, 203 ActionDest: 147 Annotation: Subtype: Link Rect: 344, 194, 356, 203 ActionDest: 156 Annotation: Subtype: Link Rect: 446, 179, 453, 191 ActionDest: 101 Annotation: Subtype: Link Rect: 508, 142, 515, 154 ActionDest: 101 Annotation: Subtype: Link Rect: 353, 116, 359, 128 ActionDest: 101 Annotation: Subtype: Link Rect: 507, 81, 514, 90 ActionDest: 147 Annotation: Subtype: Link Rect: 514, 82, 526, 90 ActionDest: 147 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 220, 672, 232, 681 ActionDest: 156 Annotation: Subtype: Link Rect: 399, 659, 411, 669 ActionDest: 156 Annotation: Subtype: Link Rect: 345, 634, 356, 643 ActionDest: 147 Annotation: Subtype: Link Rect: 357, 634, 369, 643 ActionDest: 153 Annotation: Subtype: Link Rect: 302, 622, 314, 631 ActionDest: 156 Annotation: Subtype: Link Rect: 409, 584, 421, 593 ActionDest: 150 Annotation: Subtype: Link Rect: 421, 584, 433, 593 ActionDest: 153 Annotation: Subtype: Link Rect: 368, 572, 380, 581 ActionDest: 156 Annotation: Subtype: Link Rect: 233, 107, 245, 116 ActionDest: 147 Annotation: Subtype: Link Rect: 217, 82, 229, 91 ActionDest: 147 Annotation: Subtype: Link Rect: 531, 69, 543, 79 ActionDest: 156 Annotation: Subtype: Link Rect: 544, 69, 556, 79 ActionDest: 156 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 544, 634, 556, 643 ActionDest: 153 Annotation: Subtype: Link Rect: 435, 572, 447, 581 ActionDest: 156 Annotation: Subtype: Link Rect: 544, 559, 556, 568 ActionDest: 156 Annotation: Subtype: Link Rect: 337, 496, 349, 505 ActionDest: 153 Annotation: Subtype: Link Rect: 264, 433, 276, 443 ActionDest: 156 Annotation: Subtype: Link Rect: 293, 371, 305, 380 ActionDest: 153 Annotation: Subtype: Link Rect: 419, 93, 560, 104 Annotation: Subtype: Link Rect: 166, 81, 271, 92 Page: Sequence: 17 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 473, 590, 510, 601 Annotation: Subtype: Link Rect: 419, 567, 456, 578 Annotation: Subtype: Link Rect: 459, 544, 496, 555 Annotation: Subtype: Link Rect: 503, 544, 539, 555 Annotation: Subtype: Link Rect: 493, 521, 530, 532 Annotation: Subtype: Link Rect: 210, 486, 248, 497 Annotation: Subtype: Link Rect: 254, 486, 290, 497 Annotation: Subtype: Link Rect: 136, 453, 173, 463 Annotation: Subtype: Link Rect: 179, 453, 216, 463 Annotation: Subtype: Link Rect: 168, 418, 205, 428 Annotation: Subtype: Link Rect: 59, 384, 97, 394 Annotation: Subtype: Link Rect: 436, 360, 473, 371 Annotation: Subtype: Link Rect: 501, 337, 538, 348 Annotation: Subtype: Link Rect: 282, 314, 320, 325 Annotation: Subtype: Link Rect: 167, 291, 204, 302 Annotation: Subtype: Link Rect: 419, 268, 457, 279 Annotation: Subtype: Link Rect: 59, 246, 97, 256 Annotation: Subtype: Link Rect: 520, 210, 557, 221 Annotation: Subtype: Link Rect: 59, 200, 95, 210 Annotation: Subtype: Link Rect: 132, 165, 169, 175 Annotation: Subtype: Link Rect: 59, 131, 97, 141 Annotation: Subtype: Link Rect: 103, 131, 139, 141 Annotation: Subtype: Link Rect: 95, 108, 133, 118 Annotation: Subtype: Link Rect: 139, 108, 175, 118 Annotation: Subtype: Link Rect: 86, 73, 124, 83 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 59, 722, 97, 732 Annotation: Subtype: Link Rect: 398, 698, 436, 709 Annotation: Subtype: Link Rect: 176, 676, 213, 686 Annotation: Subtype: Link Rect: 326, 640, 363, 651 Annotation: Subtype: Link Rect: 370, 640, 406, 651 Annotation: Subtype: Link Rect: 434, 617, 471, 628 Annotation: Subtype: Link Rect: 519, 606, 557, 617 Annotation: Subtype: Link Rect: 59, 595, 95, 605 Annotation: Subtype: Link Rect: 59, 572, 97, 582 Annotation: Subtype: Link Rect: 203, 560, 323, 571 Annotation: Subtype: Link Rect: 355, 537, 392, 548 Annotation: Subtype: Link Rect: 398, 537, 434, 548 Annotation: Subtype: Link Rect: 418, 514, 455, 525 Annotation: Subtype: Link Rect: 59, 492, 97, 502 Annotation: Subtype: Link Rect: 335, 468, 372, 479 Annotation: Subtype: Link Rect: 412, 445, 450, 456 Annotation: Subtype: Link Rect: 472, 433, 510, 444 Annotation: Subtype: Link Rect: 520, 410, 557, 421 Annotation: Subtype: Link Rect: 59, 400, 95, 410 Annotation: Subtype: Link Rect: 158, 365, 195, 375 Annotation: Subtype: Link Rect: 202, 365, 238, 375 Annotation: Subtype: Link Rect: 505, 341, 542, 352 Annotation: Subtype: Link Rect: 334, 318, 371, 329 Annotation: Subtype: Link Rect: 377, 318, 413, 329 Annotation: Subtype: Link Rect: 251, 295, 288, 306 Annotation: Subtype: Link Rect: 264, 272, 301, 283 Annotation: Subtype: Link Rect: 77, 250, 115, 260 Annotation: Subtype: Link Rect: 232, 215, 270, 226 Annotation: Subtype: Link Rect: 504, 192, 542, 203 Annotation: Subtype: Link Rect: 104, 169, 141, 180 Annotation: Subtype: Link Rect: 112, 146, 150, 157 Annotation: Subtype: Link Rect: 256, 134, 433, 145 Annotation: Subtype: Link Rect: 478, 123, 515, 134 Annotation: Subtype: Link Rect: 521, 123, 557, 134 Annotation: Subtype: Link Rect: 375, 100, 412, 111 Annotation: Subtype: Link Rect: 418, 100, 455, 111 Annotation: Subtype: Link Rect: 95, 66, 133, 76 Annotation: Subtype: Link Rect: 139, 66, 175, 76 Page: Sequence: 20 Annotations: Annotation: Subtype: Link Rect: 493, 721, 531, 732 Annotation: Subtype: Link Rect: 104, 699, 141, 709 Annotation: Subtype: Link Rect: 299, 675, 336, 686 Annotation: Subtype: Link Rect: 294, 652, 332, 663 Annotation: Subtype: Link Rect: 59, 630, 97, 640 Annotation: Subtype: Link Rect: 241, 606, 278, 617 Annotation: Subtype: Link Rect: 419, 594, 457, 605 Annotation: Subtype: Link Rect: 463, 594, 499, 605 Annotation: Subtype: Link Rect: 424, 571, 462, 582 Annotation: Subtype: Link Rect: 468, 571, 504, 582 Annotation: Subtype: Link Rect: 301, 548, 338, 559 Annotation: Subtype: Link Rect: 175, 515, 212, 525 Annotation: Subtype: Link Rect: 225, 480, 262, 490 Annotation: Subtype: Link Rect: 268, 480, 305, 490 Annotation: Subtype: Link Rect: 91, 457, 129, 467 Annotation: Subtype: Link Rect: 135, 457, 171, 467 Annotation: Subtype: Link Rect: 489, 445, 526, 456 Annotation: Subtype: Link Rect: 519, 422, 557, 433 Annotation: Subtype: Link Rect: 59, 411, 95, 421 Annotation: Subtype: Link Rect: 417, 387, 454, 398 Annotation: Subtype: Link Rect: 125, 364, 240, 375 Annotation: Subtype: Link Rect: 104, 342, 141, 352 Annotation: Subtype: Link Rect: 394, 319, 431, 329 Annotation: Subtype: Link Rect: 59, 296, 97, 306 Annotation: Subtype: Link Rect: 59, 273, 97, 283 Annotation: Subtype: Link Rect: 290, 249, 328, 260 Annotation: Subtype: Link Rect: 334, 249, 370, 260 Annotation: Subtype: Link Rect: 104, 227, 142, 237 Annotation: Subtype: Link Rect: 148, 227, 184, 237 Annotation: Subtype: Link Rect: 59, 204, 97, 214 Annotation: Subtype: Link Rect: 212, 181, 250, 191 Annotation: Subtype: Link Rect: 59, 146, 97, 157 Annotation: Subtype: Link Rect: 452, 123, 490, 134 Annotation: Subtype: Link Rect: 154, 89, 192, 99 Annotation: Subtype: Link Rect: 198, 89, 234, 99 Annotation: Subtype: Link Rect: 338, 65, 376, 76 Page: Sequence: 21 Annotations: Annotation: Subtype: Link Rect: 421, 721, 458, 732 Annotation: Subtype: Link Rect: 487, 686, 524, 697 Annotation: Subtype: Link Rect: 374, 653, 411, 663 Annotation: Subtype: Link Rect: 450, 629, 488, 640 Annotation: Subtype: Link Rect: 368, 606, 405, 617 Annotation: Subtype: Link Rect: 411, 606, 447, 617 Annotation: Subtype: Link Rect: 59, 584, 97, 594 Annotation: Subtype: Link Rect: 373, 560, 410, 571 Annotation: Subtype: Link Rect: 343, 525, 380, 536 Annotation: Subtype: Link Rect: 386, 525, 422, 536 Annotation: Subtype: Link Rect: 283, 502, 320, 513 Annotation: Subtype: Link Rect: 440, 479, 477, 490 Annotation: Subtype: Link Rect: 118, 446, 155, 456 Annotation: Subtype: Link Rect: 162, 446, 198, 456 Annotation: Subtype: Link Rect: 59, 411, 97, 421 Annotation: Subtype: Link Rect: 348, 387, 386, 398 Annotation: Subtype: Link Rect: 336, 365, 373, 375 Annotation: Subtype: Link Rect: 379, 365, 415, 375 Annotation: Subtype: Link Rect: 429, 330, 466, 341 Annotation: Subtype: Link Rect: 439, 307, 476, 318 Annotation: Subtype: Link Rect: 499, 295, 537, 306 Checksum: 64441153 Type: CRC32 Checksum: be7932a547c07a73b6bb796683a8d625 Type: MD5 Checksum: 090c2e3bc85ed3bdf1f56dfcf04492cbef61a0fc Type: SHA-1