3126cdbdab060c22b0df1180b1053ce8  324031.pdf
7074dbf1a10a7b3bb00847effe00d020bf2958a1  324031.pdf
95c86fcd7376268d3c1c9029296670f29b304ea52f65a4ade35dd81ae1690048  324031.pdf

Title:           Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes
Subject:         DOI: 10.1093/brain/awae205; Brain, 147, 9, 2024-06-28.; Abstract: In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution.To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired.We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes.Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary speciali
Keywords:        frontotemporal lobar degeneration; cryptic exon; human accelerated regions; TDP-43; tau; gene expression
Author:          Lorenzo Pasquini
Creator:         Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64
Producer:        PDFlib+PDI 9.0.7p3 (C++/Win64)
CreationDate:    Mon Sep  2 11:26:54 2024 CEST
ModDate:         Tue Sep  3 09:42:50 2024 CEST
Custom Metadata: yes
Metadata Stream: yes
Tagged:          yes
UserProperties:  no
Suspects:        no
Form:            AcroForm
JavaScript:      no
Pages:           16
Encrypted:       no
Page size:       612.283 x 790.866 pts
Page rot:        0
File size:       1522508 bytes
Optimized:       no
PDF version:     1.6


name                                 type              encoding         emb sub uni object ID
------------------------------------ ----------------- ---------------- --- --- --- ---------
QOLAAF+CaeciliaLTStd-Bold            Type 1C           Custom           yes yes yes   1493  0
RDUWRE+CaeciliaLTStd-BoldItalic      Type 1C           Custom           yes yes yes   1498  0
BYIQHG+CaeciliaLTStd-Roman           Type 1C           Custom           yes yes yes   1503  0
UZEBZO+CaeciliaLTStd-Heavy           Type 1C           Custom           yes yes yes     75  0
QCFNHG+CaeciliaLTStd-Italic          Type 1C           Custom           yes yes yes     80  0
NZVSYH+STIXGeneral-Regular           Type 1C           Custom           yes yes yes     85  0
Greek_Medium                         Type 1            Builtin          yes no  yes      7  0
YBNOAR+TimesNewRomanPS-ItalicMT      CID TrueType      Identity-H       yes yes yes    121  0
QJZMDP+TimesNewRomanPSMT             CID TrueType      Identity-H       yes yes yes     64  0


Jhove (Rel. 1.28.0, 2023-05-18)
 Date: 2026-01-14 04:22:37 CET
 RepresentationInformation: 324031.pdf
  ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16)
  LastModified: 2026-01-13 12:50:12 CET
  Size: 1522508
  Format: PDF
  Version: 1.6
  Status: Well-Formed and valid
  SignatureMatches:
   PDF-hul
  MIMEtype: application/pdf
  Profile: Tagged PDF
  PDFMetadata: 
   Objects: 1580
   FreeObjects: 4
   IncrementalUpdates: 4
   DocumentCatalog: 
    ViewerPreferences: 
     HideToolbar: false
     HideMenubar: false
     HideWindowUI: false
     FitWindow: false
     CenterWindow: false
     DisplayDocTitle: true
     NonFullScreenPageMode: UseNone
     Direction: L2R
     ViewArea: CropBox
     ViewClip: CropBox
     PrintArea: CropBox
     PageClip: CropBox
    PageLayout: OneColumn
    PageMode: UseOutlines
    Language: en
    Outlines: 
     Item: 
      Title: Frontotemporal lobar degeneration targetsbrain regions linked to expression of recentlyevolved genes
      Children: 
       Item: 
        Title: Introduction
        Destination: secawae205-s0
       Item: 
        Title: Materials and methods
        Destination: secawae205-s1
        Children: 
         Item: 
          Title: Participants
          Destination: secawae205-s1.1
         Item: 
          Title: Neuropathology
          Destination: secawae205-s1.2
         Item: 
          Title: Structural neuroimaging
          Destination: secawae205-s1.3
          Children: 
           Item: 
            Title: Acquisition and preprocessing
            Destination: secawae205-s1.3.1
           Item: 
            Title: W-score maps
            Destination: secawae205-s1.3.2
         Item: 
          Title: Gene expression
          Destination: secawae205-s1.4
          Children: 
           Item: 
            Title: Allen human brain atlas
            Destination: secawae205-s1.4.1
           Item: 
            Title: Human accelerated region genes
            Destination: secawae205-s1.4.2
           Item: 
            Title: Cryptic splicing genes
            Destination: secawae205-s1.4.3
           Item: 
            Title: Spatial correlation analyses
            Destination: secawae205-s1.4.4
           Item: 
            Title: Gene set enrichment analysis
            Destination: secawae205-s1.4.5
           Item: 
            Title: Graph network
            Destination: secawae205-s1.4.6
           Item: 
            Title: Gene length
            Destination: secawae205-s1.4.7
           Item: 
            Title: Disease epicentres
            Destination: secawae205-s1.4.8
       Item: 
        Title: Results
        Destination: secawae205-s2
        Children: 
         Item: 
          Title: FTLD subtypes target brain regions expressing shared and distinct genes
          Destination: secawae205-s2.1
         Item: 
          Title: Genes correlated with FTLD atrophy are enriched for HAR genes
          Destination: secawae205-s2.2
         Item: 
          Title: FTLD-TDP atrophy-correlated genes are linked to TDP-43 regulated genes
          Destination: secawae205-s2.3
         Item: 
          Title: HAR genes overlap with TDP-43 cryptic splicing genes
          Destination: secawae205-s2.4
         Item: 
          Title: Expression of cryptic splicing and HAR genes varies across FTLD-TDP subtypes and patient epicentres
          Destination: secawae205-s2.5
       Item: 
        Title: Discussion
        Destination: secawae205-s3
       Item: 
        Title: Data availability
        Destination: secawae205-s4
       Item: 
        Title: Acknowledgements
        Destination: acknow
       Item: 
        Title: Funding
        Destination: secawae205-s5
       Item: 
        Title: Competing interests
        Destination: secawae205-s6
       Item: 
        Title: Supplementary material
        Destination: secawae205-s7
       Item: 
        Title: References
        Destination: reflist
   Info: 
    Title: Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes
    Author: Lorenzo Pasquini
    Subject: DOI: 10.1093/brain/awae205; Brain, 147, 9, 2024-06-28.; Abstract: In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution.To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired.We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes.Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary speciali
    Keywords: frontotemporal lobar degeneration; cryptic exon; human accelerated regions; TDP-43; tau; gene expression
    Creator: Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64
    Producer: PDFlib+PDI 9.0.7p3 (C++/Win64)
    CreationDate: Mon Sep 02 11:56:54 CEST 2024
    ModDate: Tue Sep 03 10:12:50 CEST 2024
   ID: 0x4d1430e880c24471e38c07a09afe7423, 0x2600ea0552cfd247bc609da2401420e0
   Filters: 
    FilterPipeline: FlateDecode
    FilterPipeline: DCTDecode
   Images: 
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 2236
      ImageHeight: 254
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1143
      ImageHeight: 1653
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1266
      ImageHeight: 1485
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 650
      ImageHeight: 1114
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 650
      ImageHeight: 486
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 650
      ImageHeight: 425
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 866
      ImageHeight: 704
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1085
      ImageHeight: 1626
      BitsPerSample: 8
      BitsPerSampleUnit: integer
   Fonts: 
    Type0: 
     Font: 
      BaseFont: QJZMDP+TimesNewRomanPSMT
      Encoding: Identity-H
      ToUnicode: true
     Font: 
      BaseFont: YBNOAR+TimesNewRomanPS-ItalicMT
      Encoding: Identity-H
      ToUnicode: true
    Type1: 
     Font: 
      BaseFont: QCFNHG+CaeciliaLTStd-Italic
      FontSubset: true
      FirstChar: 1
      LastChar: 62
      FontDescriptor: 
       FontName: QCFNHG+CaeciliaLTStd-Italic
       Flags: Nonsymbolic, Italic
       FontBBox: -166, -270, 1053, 915
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: QOLAAF+CaeciliaLTStd-Bold
      FontSubset: true
      FirstChar: 1
      LastChar: 69
      FontDescriptor: 
       FontName: QOLAAF+CaeciliaLTStd-Bold
       Flags: Nonsymbolic, ForceBold
       FontBBox: -166, -273, 1141, 938
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: NZVSYH+STIXGeneral-Regular
      FontSubset: true
      FirstChar: 1
      LastChar: 8
      FontDescriptor: 
       FontName: NZVSYH+STIXGeneral-Regular
       Flags: Nonsymbolic
       FontBBox: -995, -455, 2000, 1055
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: Greek_Medium
      FirstChar: 32
      LastChar: 207
      FontDescriptor: 
       FontName: Greek_Medium
       Flags: Symbolic
       FontBBox: -50, -180, 1000, 720
       FontFile: true
      ToUnicode: true
     Font: 
      BaseFont: RDUWRE+CaeciliaLTStd-BoldItalic
      FontSubset: true
      FirstChar: 1
      LastChar: 5
      FontDescriptor: 
       FontName: RDUWRE+CaeciliaLTStd-BoldItalic
       Flags: Nonsymbolic, Italic, ForceBold
       FontBBox: -169, -273, 1082, 932
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: UZEBZO+CaeciliaLTStd-Heavy
      FontSubset: true
      FirstChar: 1
      LastChar: 31
      FontDescriptor: 
       FontName: UZEBZO+CaeciliaLTStd-Heavy
       Flags: Nonsymbolic, ForceBold
       FontBBox: -170, -277, 1146, 970
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: BYIQHG+CaeciliaLTStd-Roman
      FontSubset: true
      FirstChar: 1
      LastChar: 94
      FontDescriptor: 
       FontName: BYIQHG+CaeciliaLTStd-Roman
       Flags: Nonsymbolic
       FontBBox: -167, -270, 1136, 926
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
    CIDFontType2: 
     Font: 
      BaseFont: QJZMDP+TimesNewRomanPSMT
      CIDSystemInfo: 
       Registry: Adobe
       Registry: Identity
       Supplement: 0
      FontDescriptor: 
       FontName: QJZMDP+TimesNewRomanPSMT
       Flags: Nonsymbolic
       FontBBox: -568, -307, 2046, 1040
       FontFile2: true
     Font: 
      BaseFont: YBNOAR+TimesNewRomanPS-ItalicMT
      CIDSystemInfo: 
       Registry: Adobe
       Registry: Identity
       Supplement: 0
      FontDescriptor: 
       FontName: YBNOAR+TimesNewRomanPS-ItalicMT
       Flags: Nonsymbolic, Italic
       FontBBox: -498, -307, 1333, 1023
       FontFile2: true
   XMP: <x:xmpmeta xmlns:x="adobe:ns:meta/" x:xmptk="Adobe XMP Core 5.6-c015 84.159810, 2016/09/10-02:41:30        ">
   <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about=""
            xmlns:xmpMM="http://ns.adobe.com/xap/1.0/mm/"
            xmlns:xmpRights="http://ns.adobe.com/xap/1.0/rights/"
            xmlns:pdf="http://ns.adobe.com/pdf/1.3/"
            xmlns:dc="http://purl.org/dc/elements/1.1/"
            xmlns:prism="http://prismstandard.org/namespaces/basic/2.0/"
            xmlns:xmp="http://ns.adobe.com/xap/1.0/"
            xmlns:pdfx="http://ns.adobe.com/pdfx/1.3/"
            xmlns:pdfuaid="http://www.aiim.org/pdfua/ns/id/"
            xmlns:pdfaExtension="http://www.aiim.org/pdfa/ns/extension/"
            xmlns:pdfaSchema="http://www.aiim.org/pdfa/ns/schema#"
            xmlns:pdfaProperty="http://www.aiim.org/pdfa/ns/property#">
         <xmpMM:InstanceID>uuid:6c29bfcb-0493-4e6a-9b33-f0a80b486b62</xmpMM:InstanceID>
         <xmpMM:DocumentID>uuid:8B07BFF6-371A-7AEB-7302-BB58897D6129</xmpMM:DocumentID>
         <xmpRights:Marked>True</xmpRights:Marked>
         <pdf:Keywords>frontotemporal lobar degeneration; cryptic exon; human accelerated regions; TDP-43; tau; gene expression</pdf:Keywords>
         <pdf:Producer>PDFlib+PDI 9.0.7p3 (C++/Win64)</pdf:Producer>
         <dc:format>application/pdf</dc:format>
         <dc:identifier>10.1093/brain/awae205</dc:identifier>
         <dc:lang>en</dc:lang>
         <dc:publisher>
            <rdf:Bag>
               <rdf:li>Oxford University Press</rdf:li>
            </rdf:Bag>
         </dc:publisher>
         <dc:title>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes</rdf:li>
            </rdf:Alt>
         </dc:title>
         <dc:creator>
            <rdf:Seq>
               <rdf:li>Lorenzo Pasquini</rdf:li>
               <rdf:li>Felipe L. Pereira</rdf:li>
               <rdf:li>Sahba Seddighi</rdf:li>
               <rdf:li>Yi Zeng</rdf:li>
               <rdf:li>Yongbin Wei</rdf:li>
               <rdf:li>Ignacio Illán-Gala</rdf:li>
               <rdf:li>Sarat C. Vatsavayai</rdf:li>
               <rdf:li>Adit Friedberg</rdf:li>
               <rdf:li>Alex J. Lee</rdf:li>
               <rdf:li>Jesse A. Brown</rdf:li>
               <rdf:li>Salvatore Spina</rdf:li>
               <rdf:li>Lea T. Grinberg</rdf:li>
               <rdf:li>Daniel W. Sirkis</rdf:li>
               <rdf:li>Luke W. Bonham</rdf:li>
               <rdf:li>Jennifer S. Yokoyama</rdf:li>
               <rdf:li>Adam L. Boxer</rdf:li>
               <rdf:li>Joel H. Kramer</rdf:li>
               <rdf:li>Howard J. Rosen</rdf:li>
               <rdf:li>Jack Humphrey</rdf:li>
               <rdf:li>Aaron D. Gitler</rdf:li>
               <rdf:li>Bruce L. Miller</rdf:li>
               <rdf:li>Katherine S. Pollard</rdf:li>
               <rdf:li>Michael E. Ward</rdf:li>
               <rdf:li>William W. Seeley</rdf:li>
            </rdf:Seq>
         </dc:creator>
         <dc:description>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">DOI: 10.1093/brain/awae205; Brain, 147, 9, 2024-06-28.; Abstract: In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution.To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired.We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes.Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary speciali</rdf:li>
            </rdf:Alt>
         </dc:description>
         <dc:rights>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.</rdf:li>
            </rdf:Alt>
         </dc:rights>
         <dc:subject>
            <rdf:Bag>
               <rdf:li>frontotemporal lobar degeneration</rdf:li>
               <rdf:li>cryptic exon</rdf:li>
               <rdf:li>human accelerated regions</rdf:li>
               <rdf:li>TDP-43</rdf:li>
               <rdf:li>tau</rdf:li>
               <rdf:li>gene expression</rdf:li>
            </rdf:Bag>
         </dc:subject>
         <prism:aggregationType>Journal</prism:aggregationType>
         <prism:publicationName>Brain</prism:publicationName>
         <prism:copyright>© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.</prism:copyright>
         <prism:issn>0006-8950</prism:issn>
         <prism:elssn>1460-2156</prism:elssn>
         <prism:volume>147</prism:volume>
         <prism:number>9</prism:number>
         <prism:issueName/>
         <prism:startingPage>3032</prism:startingPage>
         <prism:endingPage>3047</prism:endingPage>
         <prism:doi>10.1093/brain/awae205</prism:doi>
         <prism:url>https://doi.org/10.1093/brain/awae205</prism:url>
         <xmp:CreateDate>2024-09-02T14:56:54+05:30</xmp:CreateDate>
         <xmp:ModifyDate>2024-09-03T13:12:50+05:30</xmp:ModifyDate>
         <xmp:CreatorTool>Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64</xmp:CreatorTool>
         <xmp:MetadataDate>2024-09-03T13:12:50+05:30</xmp:MetadataDate>
         <pdfx:EPSprocessor>PStill version 1.84.42</pdfx:EPSprocessor>
         <pdfuaid:part>1</pdfuaid:part>
         <pdfaExtension:schemas>
            <rdf:Bag>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:schema>PDF/UA Universal Accessibility Schema</pdfaSchema:schema>
                  <pdfaSchema:namespaceURI>http://www.aiim.org/pdfua/ns/id/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>pdfuaid</pdfaSchema:prefix>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:name>part</pdfaProperty:name>
                           <pdfaProperty:valueType>Integer</pdfaProperty:valueType>
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Indicates, which part of ISO 14289 standard is followed</pdfaProperty:description>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
            </rdf:Bag>
         </pdfaExtension:schemas>
      </rdf:Description>
   </rdf:RDF>
</x:xmpmeta>
   Pages: 
    Page: 
     Sequence: 1
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 153, 565, 159, 577
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 161, 565, 167, 577
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 268, 565, 273, 577
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 372, 565, 377, 577
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 429, 565, 435, 577
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 438, 561, 448, 571
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 529, 565, 534, 577
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 47, 547, 57, 557
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 166, 551, 171, 563
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 174, 551, 179, 563
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 182, 551, 187, 563
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 309, 551, 315, 563
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 406, 551, 411, 563
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 414, 551, 419, 563
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 488, 551, 493, 563
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 138, 538, 144, 549
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 147, 533, 157, 543
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 253, 538, 259, 549
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 262, 533, 272, 543
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 367, 538, 372, 549
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 375, 538, 380, 549
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 483, 538, 488, 549
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 153, 524, 159, 535
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 161, 524, 167, 535
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 301, 524, 307, 535
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 309, 524, 315, 535
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 409, 524, 414, 535
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 507, 524, 512, 535
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 148, 510, 153, 521
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 252, 510, 262, 521
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 358, 510, 363, 521
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 455, 510, 460, 521
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 165, 496, 176, 507
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 178, 496, 189, 507
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 191, 496, 201, 507
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 204, 496, 214, 507
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 313, 496, 318, 507
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 454, 496, 459, 507
       Flags: Print
       Destination: 1460
      Annotation: 
       Subtype: Link
       Rect: 462, 496, 467, 507
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 116, 453, 287, 462
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 374, 40, 516, 46
       Flags: Print
    Page: 
     Sequence: 2
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 90, 547, 211, 556
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 90, 513, 178, 522
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 265, 390, 269, 398
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 270, 390, 273, 398
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 219, 368, 223, 376
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 224, 368, 227, 376
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 156, 346, 159, 354
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 165, 324, 168, 332
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 170, 324, 173, 332
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 226, 313, 230, 321
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 231, 313, 234, 321
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 180, 291, 183, 299
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 154, 269, 157, 277
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 252, 236, 256, 244
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 292, 104, 295, 111
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 297, 104, 300, 111
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 237, 71, 240, 78
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 435, 442, 438, 450
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 558, 442, 564, 450
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 550, 431, 556, 438
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 558, 431, 564, 438
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 452, 420, 455, 427
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 431, 353, 446, 360
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 391, 330, 406, 338
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 395, 285, 410, 292
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 482, 251, 496, 259
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 465, 228, 471, 236
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 472, 228, 479, 236
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 427, 183, 433, 191
       Flags: Print
       Destination: 58
    Page: 
     Sequence: 3
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 272, 585, 278, 593
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 228, 574, 234, 582
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 128, 563, 134, 571
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 251, 552, 257, 560
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 181, 442, 187, 450
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 229, 420, 235, 428
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 82, 395, 111, 402
       Flags: Print
       Destination: 13
      Annotation: 
       Subtype: Link
       Rect: 250, 326, 253, 333
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 255, 326, 261, 333
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 262, 326, 268, 333
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 267, 315, 273, 322
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 274, 315, 280, 322
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 421, 720, 427, 727
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 367, 684, 551, 691
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 522, 569, 529, 576
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 530, 569, 536, 576
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 549, 525, 555, 532
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 506, 514, 513, 521
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 414, 499, 501, 507
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 370, 282, 555, 289
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 271, 452, 278
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 348, 188, 514, 196
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 411, 181, 417, 188
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 434, 126, 440, 133
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 345, 111, 481, 119
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 484, 115, 490, 122
       Flags: Print
       Destination: 62
    Page: 
     Sequence: 4
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 179, 414, 289, 421
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 294, 417, 300, 425
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 97, 359, 258, 366
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 83, 260, 174, 267
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 107, 219, 113, 227
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 59, 205, 296, 212
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 289, 137, 292, 144
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 141, 115, 144, 122
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 190, 71, 196, 78
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 204, 67, 300, 75
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 56, 56, 107, 64
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 404, 412, 419, 419
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 445, 390, 451, 397
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 462, 379, 468, 386
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 470, 379, 476, 386
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 374, 324, 381, 331
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 356, 269, 362, 276
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 455, 192, 461, 199
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 411, 112, 555, 119
       Flags: Print
    Page: 
     Sequence: 5
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 201, 469, 207, 477
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 209, 469, 215, 477
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 217, 469, 223, 477
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 183, 436, 189, 444
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 196, 433, 291, 441
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 47, 422, 193, 430
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 233, 403, 239, 411
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 50, 378, 126, 386
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 176, 356, 291, 364
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 47, 345, 143, 353
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 47, 268, 287, 276
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 366, 549, 372, 557
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 436, 505, 442, 513
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 415, 494, 422, 502
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 471, 335, 477, 342
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 419, 205, 555, 212
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 194, 384, 201
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 346, 183, 453, 190
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 335, 71, 350, 78
       Flags: Print
       Destination: 62
    Page: 
     Sequence: 6
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 236, 665, 242, 672
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 286, 390, 292, 397
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 294, 390, 300, 397
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 286, 368, 292, 375
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 294, 368, 300, 375
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 205, 210, 283, 218
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 75, 159, 81, 166
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 220, 100, 296, 108
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 533, 727, 560, 735
       Flags: Print
       Destination: 25
      Annotation: 
       Subtype: Link
       Rect: 437, 687, 443, 694
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 476, 651, 502, 658
       Flags: Print
       Destination: 25
      Annotation: 
       Subtype: Link
       Rect: 345, 607, 370, 614
       Flags: Print
       Destination: 25
      Annotation: 
       Subtype: Link
       Rect: 484, 563, 560, 570
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 558, 544, 564, 551
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 439, 533, 445, 540
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 398, 500, 404, 507
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 342, 452, 360, 460
       Flags: Print
       Destination: 29
      Annotation: 
       Subtype: Link
       Rect: 377, 452, 452, 460
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 388, 430, 411, 438
       Flags: Print
       Destination: 29
      Annotation: 
       Subtype: Link
       Rect: 395, 423, 401, 430
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 381, 364, 433, 372
       Flags: Print
       Destination: 29
      Annotation: 
       Subtype: Link
       Rect: 374, 353, 397, 361
       Flags: Print
       Destination: 29
      Annotation: 
       Subtype: Link
       Rect: 540, 254, 564, 262
       Flags: Print
       Destination: 34
      Annotation: 
       Subtype: Link
       Rect: 337, 243, 426, 251
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 431, 247, 434, 254
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 442, 199, 466, 207
       Flags: Print
       Destination: 34
      Annotation: 
       Subtype: Link
       Rect: 357, 188, 379, 196
       Flags: Print
       Destination: 34
      Annotation: 
       Subtype: Link
       Rect: 434, 111, 514, 119
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 423, 56, 498, 64
       Flags: Print
    Page: 
     Sequence: 7
    Page: 
     Sequence: 8
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 385, 93, 392, 100
       Flags: Print
       Destination: 62
    Page: 
     Sequence: 9
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 112, 427, 190, 435
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 201, 368, 216, 375
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 222, 364, 247, 372
       Flags: Print
       Destination: 34
      Annotation: 
       Subtype: Link
       Rect: 240, 280, 246, 287
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 248, 280, 254, 287
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 131, 269, 137, 276
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 141, 265, 227, 273
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 159, 254, 249, 262
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 216, 210, 240, 218
       Flags: Print
       Destination: 34
      Annotation: 
       Subtype: Link
       Rect: 81, 122, 105, 130
       Flags: Print
       Destination: 34
      Annotation: 
       Subtype: Link
       Rect: 378, 78, 458, 86
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 273, 481, 276, 488
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 78, 472, 84, 479
       Flags: Print
       Destination: 62
    Page: 
     Sequence: 10
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 59, 694, 145, 702
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 88, 596, 114, 603
       Flags: Print
       Destination: 34
      Annotation: 
       Subtype: Link
       Rect: 119, 599, 125, 606
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 169, 518, 215, 526
       Flags: Print
       Destination: 34
      Annotation: 
       Subtype: Link
       Rect: 259, 463, 284, 471
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 56, 452, 148, 460
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 150, 423, 165, 430
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 285, 412, 300, 419
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 294, 368, 300, 375
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 207, 331, 296, 339
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 56, 309, 144, 317
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 215, 291, 221, 298
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 243, 287, 300, 295
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 56, 276, 85, 284
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 131, 243, 216, 251
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 139, 232, 223, 240
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 271, 155, 296, 163
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 115, 133, 140, 141
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 112, 122, 135, 130
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 200, 89, 296, 97
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 494, 424, 513, 431
       Flags: Print
       Destination: 45
      Annotation: 
       Subtype: Link
       Rect: 537, 247, 543, 254
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 338, 203, 345, 210
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 346, 203, 353, 210
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 403, 192, 406, 199
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 407, 192, 413, 199
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 415, 192, 421, 199
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 373, 159, 379, 166
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 380, 159, 387, 166
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 471, 133, 562, 141
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 518, 104, 525, 111
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 526, 104, 532, 111
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 534, 104, 540, 111
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 382, 67, 408, 75
       Flags: Print
       Destination: 50
    Page: 
     Sequence: 11
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 50, 331, 147, 339
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 181, 288, 206, 295
       Flags: Print
       Destination: 50
      Annotation: 
       Subtype: Link
       Rect: 50, 266, 75, 273
       Flags: Print
       Destination: 50
      Annotation: 
       Subtype: Link
       Rect: 110, 255, 134, 262
       Flags: Print
       Destination: 50
      Annotation: 
       Subtype: Link
       Rect: 129, 100, 180, 108
       Flags: Print
       Destination: 50
      Annotation: 
       Subtype: Link
       Rect: 117, 78, 141, 86
       Flags: Print
       Destination: 50
      Annotation: 
       Subtype: Link
       Rect: 340, 386, 365, 394
       Flags: Print
       Destination: 50
      Annotation: 
       Subtype: Link
       Rect: 460, 364, 484, 372
       Flags: Print
       Destination: 50
      Annotation: 
       Subtype: Link
       Rect: 398, 309, 444, 317
       Flags: Print
       Destination: 50
      Annotation: 
       Subtype: Link
       Rect: 378, 170, 381, 177
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 382, 115, 388, 122
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 481, 82, 487, 89
       Flags: Print
       Destination: 62
    Page: 
     Sequence: 12
    Page: 
     Sequence: 13
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 264, 731, 270, 738
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 285, 588, 291, 595
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 92, 555, 98, 562
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 114, 533, 120, 540
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 230, 434, 237, 441
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 238, 434, 244, 441
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 76, 423, 83, 430
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 201, 423, 207, 430
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 209, 423, 215, 430
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 285, 423, 291, 430
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 174, 390, 180, 397
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 182, 390, 188, 397
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 65, 302, 71, 309
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 264, 258, 267, 265
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 269, 258, 275, 265
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 277, 258, 283, 265
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 285, 258, 291, 265
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 170, 225, 176, 232
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 277, 203, 284, 210
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 252, 170, 259, 177
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 160, 137, 166, 144
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 549, 632, 555, 639
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 426, 599, 432, 606
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 333, 555, 339, 562
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 340, 555, 346, 562
       Flags: Print
       Destination: 62
      Annotation: 
       Subtype: Link
       Rect: 395, 511, 401, 518
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 402, 511, 408, 518
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 484, 467, 490, 474
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 387, 456, 393, 463
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 395, 456, 401, 463
       Flags: Print
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 331, 445, 338, 452
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 403, 361, 491, 368
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 530, 361, 555, 368
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 350, 379, 357
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 466, 350, 555, 357
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 339, 408, 346
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 365, 320, 371, 328
       Flags: Print
       Destination: 71
      Annotation: 
       Subtype: Link
       Rect: 376, 317, 551, 324
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 295, 399, 302
       Flags: Print
    Page: 
     Sequence: 14
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 56, 446, 146, 453
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 56, 391, 60, 399
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 360, 60, 367
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 328, 60, 336
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 297, 60, 305
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 266, 60, 273
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 244, 60, 252
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 213, 60, 220
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 181, 60, 189
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 150, 60, 158
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 129, 65, 136
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 56, 87, 65, 94
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 727, 329, 735
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 685, 329, 693
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 654, 329, 662
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 622, 329, 630
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 591, 329, 599
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 560, 329, 567
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 518, 329, 525
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 486, 329, 493
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 444, 329, 452
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 423, 329, 430
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 391, 329, 399
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 349, 329, 357
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 328, 329, 336
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 297, 329, 305
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 320, 266, 329, 273
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 370, 244, 520, 252
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 320, 234, 329, 241
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 320, 213, 329, 220
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 320, 171, 329, 178
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 320, 139, 329, 147
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 320, 108, 329, 115
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 320, 76, 329, 84
       Flags: Print
       Destination: 5
    Page: 
     Sequence: 15
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 47, 727, 56, 735
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 696, 56, 704
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 665, 56, 672
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 643, 56, 651
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 622, 56, 630
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 591, 56, 599
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 560, 56, 567
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 528, 56, 535
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 496, 56, 504
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 465, 56, 472
       Flags: Print
       Destination: 5
      Annotation: 
       Subtype: Link
       Rect: 47, 433, 56, 441
       Flags: Print
       Destination: 13
      Annotation: 
       Subtype: Link
       Rect: 47, 402, 56, 410
       Flags: Print
       Destination: 13
      Annotation: 
       Subtype: Link
       Rect: 47, 370, 56, 378
       Flags: Print
       Destination: 13
      Annotation: 
       Subtype: Link
       Rect: 47, 339, 56, 346
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 47, 308, 56, 315
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 47, 276, 56, 283
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 47, 244, 56, 252
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 47, 213, 56, 220
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 47, 171, 56, 178
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 47, 150, 56, 158
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 47, 129, 56, 136
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 47, 108, 56, 116
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 47, 78, 56, 85
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 311, 727, 320, 735
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 311, 696, 320, 704
       Flags: Print
       Destination: 17
      Annotation: 
       Subtype: Link
       Rect: 311, 665, 320, 672
       Flags: Print
       Destination: 21
      Annotation: 
       Subtype: Link
       Rect: 311, 633, 320, 640
       Flags: Print
       Destination: 21
      Annotation: 
       Subtype: Link
       Rect: 311, 601, 320, 609
       Flags: Print
       Destination: 21
      Annotation: 
       Subtype: Link
       Rect: 311, 570, 320, 577
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 538, 320, 546
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 496, 320, 504
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 465, 320, 472
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 423, 320, 430
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 391, 320, 399
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 349, 320, 357
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 318, 320, 325
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 286, 320, 294
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 255, 320, 262
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 223, 320, 231
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 192, 320, 200
       Flags: Print
       Destination: 40
      Annotation: 
       Subtype: Link
       Rect: 311, 161, 320, 168
       Flags: Print
       Destination: 45
      Annotation: 
       Subtype: Link
       Rect: 311, 119, 320, 126
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 311, 88, 320, 95
       Flags: Print
       Destination: 54
    Page: 
     Sequence: 16
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 56, 727, 65, 735
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 56, 696, 65, 704
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 56, 665, 65, 672
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 56, 643, 65, 651
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 56, 612, 65, 619
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 56, 580, 65, 588
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 56, 560, 65, 567
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 56, 528, 65, 535
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 320, 727, 329, 735
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 320, 696, 329, 704
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 320, 665, 329, 672
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 320, 633, 329, 640
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 320, 601, 329, 609
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 320, 549, 329, 557
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 320, 518, 329, 525
       Flags: Print
       Destination: 54
      Annotation: 
       Subtype: Link
       Rect: 498, 518, 555, 525
       Flags: Print
  Checksum: b883e4c8
   Type: CRC32
  Checksum: 3126cdbdab060c22b0df1180b1053ce8
   Type: MD5
  Checksum: 7074dbf1a10a7b3bb00847effe00d020bf2958a1
   Type: SHA-1
  Checksum: 95c86fcd7376268d3c1c9029296670f29b304ea52f65a4ade35dd81ae1690048
   Type: SHA-256