3bf84e594f37d79055b7ca5fafe3464d  301949.pdf
f572194461b17477704a25f42e76b71a49ef9f50  301949.pdf
f584a791391fa8f44e09f3f5797b5014ce605595d55cd5f260655c475858d648  301949.pdf

Keywords:        Plasmodium vivax, intrasplenic infections, extracellular vesicles (EVs), CRISPR/Ca9, single-cell RNASeq (scRNASeq), spleen fibroblasts
Custom Metadata: no
Metadata Stream: yes
Tagged:          no
UserProperties:  no
Suspects:        no
Form:            none
JavaScript:      no
Pages:           14
Encrypted:       no
Page size:       595.389 x 841.663 pts (A4)
Page rot:        0
File size:       3772493 bytes
Optimized:       no
PDF version:     1.4


name                                 type              encoding         emb sub uni object ID
------------------------------------ ----------------- ---------------- --- --- --- ---------
BBDCGO+AdvTT2c8ce45a                 Type 1C           WinAnsi          yes yes no     550  0
BBDCGP+AdvTTc8b77491.I               Type 1C           WinAnsi          yes yes no     547  0
BBDCHA+AdvTT2c8ce45a+fb              Type 1C           Custom           yes yes yes    548  0
BBDDFL+AdvTT2c8ce45a+20              Type 1C           WinAnsi          yes yes no     549  0
BBDCED+AdvTT749c1f5a.I               Type 1C           WinAnsi          yes yes no     523  0
BBDCEE+AdvTTd3a5f740                 Type 1C           WinAnsi          yes yes no     524  0
BBDCEF+AdvTTd3a5f740+20              Type 1C           WinAnsi          yes yes no     525  0
BBDCEG+AdvPSA18C                     Type 1C           WinAnsi          yes yes no     526  0
BBDCFH+AdvTTd3a5f740+01              Type 1C           MacRoman         yes yes no     527  0
BBDCFI+AdvTT9b12cd41                 Type 1C           WinAnsi          yes yes no     528  0
BBDCFJ+AdvTT9b12cd41+01              Type 1C           MacRoman         yes yes no     529  0
BBDCFK+AdvPSA323                     Type 1C           WinAnsi          yes yes no     530  0
BBDCFL+AdvTT9b12cd41+20              Type 1C           WinAnsi          yes yes no     522  0
BBDCFM+AdvTTd168d80a.I               Type 1C           WinAnsi          yes yes no     539  0
BBDCFN+AdvTT9b12cd41+fb              Type 1C           Custom           yes yes yes    540  0
BBDDHL+AdvOT1ef757c0                 Type 1C           WinAnsi          yes yes no     293  0
BBDDHM+AdvOT7d6df7ab.I               Type 1C           WinAnsi          yes yes no     304  0
BBDDHN+AdvOT1ef757c0+fb              Type 1C           Custom           yes yes yes    305  0
BBDDIN+AdvOT1ef757c0+20              Type 1C           WinAnsi          yes yes no     311  0
BBDDIO+AdvTT58d178b9+03              Type 1C           Custom           yes yes yes    303  0
BBDDIP+AdvOT3f84ef53                 Type 1C           WinAnsi          yes yes no     298  0
BBDDKA+AdvOTd877c31c+21              Type 1C           WinAnsi          yes yes no     321  0
BBDDKB+AdvOTd877c31c                 Type 1C           WinAnsi          yes yes no     315  0
BBDDLC+AdvOT1ef757c0+22              Type 1C           Custom           yes yes no     318  0
BBDDMC+AdvTTd3a5f740+fb              Type 1C           Custom           yes yes yes    324  0
HelveticaNeueLTStd-Bd                Type 1C           WinAnsi          yes no  no     330  0
BBDNCH+AdvOT1ef757c0+01              Type 1C           MacRoman         yes yes no     332  0


Jhove (Rel. 1.28.0, 2023-05-18)
 Date: 2024-11-07 02:44:53 CET
 RepresentationInformation: 301949.pdf
  ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16)
  LastModified: 2024-11-06 12:41:01 CET
  Size: 3772493
  Format: PDF
  Version: 1.4
  Status: Well-Formed and valid
  SignatureMatches:
   PDF-hul
  MIMEtype: application/pdf
  PDFMetadata: 
   Objects: 641
   FreeObjects: 3
   IncrementalUpdates: 2
   DocumentCatalog: 
    PageLayout: SinglePage
    PageMode: UseOutlines
    Outlines: 
     Item: 
      Title: Plasmodium vivax spleen-dependent protein 1 and its role in extracellular vesicles-mediated intrasplenic infections
      Destination: bmark_-2122299776
      Children: 
       Item: 
        Title: Introduction
        Destination: s1
       Item: 
        Title: Material and methods
        Destination: s2
        Children: 
         Item: 
          Title: Human plasma samples
          Destination: s2_1
         Item: 
          Title: Plasmid constructs, parasite culture and transfection
          Destination: s2_2
         Item: 
          Title: Genomic integration and transcript detection
          Destination: s2_3
         Item: 
          Title: Western blotting
          Destination: s2_4
         Item: 
          Title: Immunogenicity prediction and peptide selection
          Destination: s2_5
         Item: 
          Title: Generation of polyclonal antibodies against PvSDP1 and antibody testing through ELISA
          Destination: s2_6
         Item: 
          Title: Indirect immunofluorescence assay
          Destination: s2_7
         Item: 
          Title: Extracellular vesicles isolation, bead based assay characterization & EVs pooling.
          Destination: s2_8
         Item: 
          Title: EVs isolation via direct immunoaffinity capture of CD71+
          Destination: s2_9
         Item: 
          Title: Human spleen fibroblast culture and stimulation with Evs
          Destination: s2_10
         Item: 
          Title: P. falciparum 3D7_PvSDP1 functional binding assay
          Destination: s2_11
         Item: 
          Title: Binding inhibition assay using anti-PvSDP1 antibody
          Destination: s2_12
         Item: 
          Title: Single-cell RNA
          Destination: s2_13
         Item: 
          Title: Single-cell RNA-Seq data processing
          Destination: s2_14
         Item: 
          Title: Identification of differentially expressed genes
          Destination: s2_15
         Item: 
          Title: Single-Cell RNAseq validation through RT and qPCR of EVs-Stimulated hSFs
          Destination: s2_16
       Item: 
        Title: Results
        Destination: s3
        Children: 
         Item: 
          Title: Generation of a transgenic P. falciparum clonal line expressing PvSDP1
          Destination: s3_1
         Item: 
          Title: Characterization of P. falciparum 3D7_PvSDP1
          Destination: s3_2
         Item: 
          Title: Immunofluorescence analysis reveals membrane localization of PvSDP1
          Destination: s3_3
         Item: 
          Title: PvSDP1 is expressed in the membrane of reticulocytes in natural infections
          Destination: s3_4
         Item: 
          Title: Cytoadherence of P. falciparum 3D7_PvSDP1 to human spleen fibroblasts
          Destination: s3_5
         Item: 
          Title: Immunocaptured EVs increase binding to hSFs
          Destination: s3_6
         Item: 
          Title: Anti-PvSDP1 polyclonal antibodies block binding of the transgenic P. falciparum 3D7_PvSDP1 line to hSF
          Destination: s3_7
         Item: 
          Title: Single-cell RNAseq showed increased adhesin expression in PvEVs-treated hSFs
          Destination: s3_8
       Item: 
        Title: Discussion
        Destination: s4
       Item: 
        Title: Data availability statement
        Destination: s5
       Item: 
        Title: Ethics statement
        Destination: s6
       Item: 
        Title: Author contributions
        Destination: s7
       Item: 
        Title: Funding
        Destination: bmark_1865464027
       Item: 
        Title: Acknowledgments
        Destination: bmark_-366698314
       Item: 
        Title: Conflict of interest
        Destination: bmark_1089982005
       Item: 
        Title: Publisher’s note
        Destination: bmark_-1256977648
       Item: 
        Title: Supplementary material
        Destination: bmark_632582120
       Item: 
        Title: References
        Destination: bmark_2090415954
   Info: 
    Keywords: Plasmodium vivax, intrasplenic infections, extracellular vesicles (EVs), CRISPR/Ca9, single-cell RNASeq (scRNASeq), spleen fibroblasts
   ID: 0x8cd9b5a4beabae5db6114c42123a5b61, 0x80c783d7dd0db7478ce6e792bd9fceca
   Filters: 
    FilterPipeline: FlateDecode
    FilterPipeline: DCTDecode
   Images: 
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 2919
      ImageHeight: 577
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 2339
      ImageHeight: 1204
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 1818
      ImageHeight: 1866
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1918
      ImageHeight: 1852
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1984
      ImageHeight: 2016
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 2020
      ImageHeight: 2267
      BitsPerSample: 8
      BitsPerSampleUnit: integer
   Fonts: 
    Type1: 
     Font: 
      BaseFont: BBDDKA+AdvOTd877c31c+21
      FontSubset: true
      FirstChar: 153
      LastChar: 153
      FontDescriptor: 
       FontName: BBDDKA+AdvOTd877c31c+21
       Flags: Nonsymbolic
       FontBBox: -10, -250, 1145, 864
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDDMC+AdvTTd3a5f740+fb
      FontSubset: true
      FirstChar: 1
      LastChar: 3
      FontDescriptor: 
       FontName: BBDDMC+AdvTTd3a5f740+fb
       Flags: Symbolic
       FontBBox: 0, 0, 906, 708
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: BBDCFL+AdvTT9b12cd41+20
      FontSubset: true
      FirstChar: 146
      LastChar: 146
      FontDescriptor: 
       FontName: BBDCFL+AdvTT9b12cd41+20
       Flags: Nonsymbolic
       FontBBox: -114, -166, 1010, 864
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: HelveticaNeueLTStd-Bd
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: HelveticaNeueLTStd-Bd
       Flags: Nonsymbolic, ForceBold
       FontBBox: -166, -218, 1078, 975
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDCED+AdvTT749c1f5a.I
      FontSubset: true
      FirstChar: 46
      LastChar: 120
      FontDescriptor: 
       FontName: BBDCED+AdvTT749c1f5a.I
       Flags: Serif, Nonsymbolic
       FontBBox: -145, -208, 989, 885
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDCEE+AdvTTd3a5f740
      FontSubset: true
      FirstChar: 38
      LastChar: 224
      FontDescriptor: 
       FontName: BBDCEE+AdvTTd3a5f740
       Flags: Serif, Nonsymbolic
       FontBBox: -52, -208, 916, 885
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDNCH+AdvOT1ef757c0+01
      FontSubset: true
      FirstChar: 245
      LastChar: 245
      FontDescriptor: 
       FontName: BBDNCH+AdvOT1ef757c0+01
       Flags: Serif, Nonsymbolic
       FontBBox: -20, -250, 947, 854
       FontFile3: true
      Encoding: MacRomanEncoding
     Font: 
      BaseFont: BBDCEF+AdvTTd3a5f740+20
      FontSubset: true
      FirstChar: 134
      LastChar: 146
      FontDescriptor: 
       FontName: BBDCEF+AdvTTd3a5f740+20
       Flags: Nonsymbolic
       FontBBox: -114, -166, 1062, 864
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDCEG+AdvPSA18C
      FontSubset: true
      FirstChar: 180
      LastChar: 180
      FontDescriptor: 
       FontName: BBDCEG+AdvPSA18C
       Flags: Nonsymbolic
       FontBBox: -156, -208, 1125, 802
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDCFH+AdvTTd3a5f740+01
      FontSubset: true
      FirstChar: 245
      LastChar: 245
      FontDescriptor: 
       FontName: BBDCFH+AdvTTd3a5f740+01
       Flags: Nonsymbolic
       FontBBox: -52, -208, 947, 885
       FontFile3: true
      Encoding: MacRomanEncoding
     Font: 
      BaseFont: BBDCFI+AdvTT9b12cd41
      FontSubset: true
      FirstChar: 37
      LastChar: 224
      FontDescriptor: 
       FontName: BBDCFI+AdvTT9b12cd41
       Flags: Serif, Nonsymbolic
       FontBBox: -52, -208, 906, 875
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDCFJ+AdvTT9b12cd41+01
      FontSubset: true
      FirstChar: 245
      LastChar: 245
      FontDescriptor: 
       FontName: BBDCFJ+AdvTT9b12cd41+01
       Flags: Nonsymbolic
       FontBBox: -52, -208, 958, 875
       FontFile3: true
      Encoding: MacRomanEncoding
     Font: 
      BaseFont: BBDCFK+AdvPSA323
      FontSubset: true
      FirstChar: 180
      LastChar: 184
      FontDescriptor: 
       FontName: BBDCFK+AdvPSA323
       Flags: Nonsymbolic
       FontBBox: -156, -239, 1104, 770
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDCFM+AdvTTd168d80a.I
      FontSubset: true
      FirstChar: 45
      LastChar: 120
      FontDescriptor: 
       FontName: BBDCFM+AdvTTd168d80a.I
       Flags: Serif, Nonsymbolic
       FontBBox: -145, -208, 968, 875
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDCFN+AdvTT9b12cd41+fb
      FontSubset: true
      FirstChar: 1
      LastChar: 3
      FontDescriptor: 
       FontName: BBDCFN+AdvTT9b12cd41+fb
       Flags: Symbolic
       FontBBox: 0, 0, 854, 697
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: BBDCGP+AdvTTc8b77491.I
      FontSubset: true
      FirstChar: 80
      LastChar: 120
      FontDescriptor: 
       FontName: BBDCGP+AdvTTc8b77491.I
       Flags: Serif, Nonsymbolic
       FontBBox: -145, -208, 1020, 895
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDCHA+AdvTT2c8ce45a+fb
      FontSubset: true
      FirstChar: 1
      LastChar: 1
      FontDescriptor: 
       FontName: BBDCHA+AdvTT2c8ce45a+fb
       Flags: Symbolic
       FontBBox: 0, 0, 947, 708
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: BBDDFL+AdvTT2c8ce45a+20
      FontSubset: true
      FirstChar: 134
      LastChar: 134
      FontDescriptor: 
       FontName: BBDDFL+AdvTT2c8ce45a+20
       Flags: Nonsymbolic
       FontBBox: -125, -166, 1125, 864
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDDHL+AdvOT1ef757c0
      FontSubset: true
      FirstChar: 35
      LastChar: 248
      FontDescriptor: 
       FontName: BBDDHL+AdvOT1ef757c0
       Flags: Serif, Nonsymbolic
       FontBBox: -20, -250, 947, 854
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDCGO+AdvTT2c8ce45a
      FontSubset: true
      FirstChar: 40
      LastChar: 120
      FontDescriptor: 
       FontName: BBDCGO+AdvTT2c8ce45a
       Flags: Serif, Nonsymbolic
       FontBBox: -52, -208, 947, 895
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDDIP+AdvOT3f84ef53
      FontSubset: true
      FirstChar: 68
      LastChar: 109
      FontDescriptor: 
       FontName: BBDDIP+AdvOT3f84ef53
       Flags: Nonsymbolic
       FontBBox: -177, -291, 1083, 1000
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDDIO+AdvTT58d178b9+03
      FontSubset: true
      FirstChar: 0
      LastChar: 0
      FontDescriptor: 
       FontName: BBDDIO+AdvTT58d178b9+03
       Flags: Symbolic
       FontBBox: -645, -354, 916, 895
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: BBDDHM+AdvOT7d6df7ab.I
      FontSubset: true
      FirstChar: 40
      LastChar: 124
      FontDescriptor: 
       FontName: BBDDHM+AdvOT7d6df7ab.I
       Flags: Serif, Nonsymbolic
       FontBBox: -135, -250, 1000, 854
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDDHN+AdvOT1ef757c0+fb
      FontSubset: true
      FirstChar: 1
      LastChar: 3
      FontDescriptor: 
       FontName: BBDDHN+AdvOT1ef757c0+fb
       Flags: Symbolic
       FontBBox: 0, -10, 781, 708
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: BBDDIN+AdvOT1ef757c0+20
      FontSubset: true
      FirstChar: 146
      LastChar: 150
      FontDescriptor: 
       FontName: BBDDIN+AdvOT1ef757c0+20
       Flags: Nonsymbolic
       FontBBox: -135, -187, 1010, 833
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDDKB+AdvOTd877c31c
      FontSubset: true
      FirstChar: 174
      LastChar: 174
      FontDescriptor: 
       FontName: BBDDKB+AdvOTd877c31c
       Flags: Nonsymbolic
       FontBBox: -62, -208, 927, 958
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: BBDDLC+AdvOT1ef757c0+22
      FontSubset: true
      FirstChar: 21
      LastChar: 21
      FontDescriptor: 
       FontName: BBDDLC+AdvOT1ef757c0+22
       Flags: Nonsymbolic
       FontBBox: -135, -166, 697, 916
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
   XMP: <x:xmpmeta xmlns:x='adobe:ns:meta/' x:xmptk='Image::ExifTool 12.52'>
<rdf:RDF xmlns:rdf='http://www.w3.org/1999/02/22-rdf-syntax-ns#'>

 <rdf:Description rdf:about=''
  xmlns:dc='http://purl.org/dc/elements/1.1/'>
  <dc:creator>
   <rdf:Seq>
    <rdf:li>Alberto Ayllon-Hermida</rdf:li>
    <rdf:li>Marc Nicolau-Fernandez</rdf:li>
    <rdf:li>Ane M. Larrinaga</rdf:li>
    <rdf:li>Iris Aparici-Herraiz</rdf:li>
    <rdf:li>Elisabet Tintó-Font</rdf:li>
    <rdf:li>Oriol Llorà-Batlle</rdf:li>
    <rdf:li>Agnes Orban</rdf:li>
    <rdf:li>María Fernanda Yasnot</rdf:li>
    <rdf:li>Mariona Graupera</rdf:li>
    <rdf:li>Manel Esteller</rdf:li>
    <rdf:li>Jean Popovici</rdf:li>
    <rdf:li>Alfred Cortés</rdf:li>
    <rdf:li>Hernando A. del Portillo</rdf:li>
    <rdf:li>Carmen Fernandez-Becerra</rdf:li>
   </rdf:Seq>
  </dc:creator>
  <dc:description>
   <rdf:Alt>
    <rdf:li xml:lang='x-default'>Ayllon-Hermida A, Nicolau-Fernandez M, Larrinaga AM, Aparici-Herraiz I, Tintó-Font E, Llorà-Batlle O, Orban A, Yasnot MF, Graupera M, Esteller M, Popovici J, Cortés A, del Portillo HA and Fernandez-Becerra C (2024) Plasmodium vivax spleen-dependent protein 1 and its role in extracellular vesicles-mediated intrasplenic infections. Front. Cell. Infect. Microbiol. 14:1408451</rdf:li>
   </rdf:Alt>
  </dc:description>
  <dc:rights>
   <rdf:Alt>
    <rdf:li xml:lang='x-default'>Copyright © 2024 Ayllon-Hermida, Nicolau-Fernandez, Larrinaga, Aparici-Herraiz, Tintó-Font, Llorà-Batlle, Orban, Yasnot, Graupera, Esteller, Popovici, Cortés, del Portillo and Fernandez-Becerra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</rdf:li>
   </rdf:Alt>
  </dc:rights>
  <dc:subject>
   <rdf:Bag>
    <rdf:li>Plasmodium vivax</rdf:li>
    <rdf:li>intrasplenic infections</rdf:li>
    <rdf:li>extracellular vesicles (EVs)</rdf:li>
    <rdf:li>CRISPR/Ca9</rdf:li>
    <rdf:li>single-cell RNASeq (scRNASeq)</rdf:li>
    <rdf:li>spleen fibroblasts</rdf:li>
   </rdf:Bag>
  </dc:subject>
  <dc:title>
   <rdf:Alt>
    <rdf:li xml:lang='x-default'>Plasmodium vivax spleen-dependent protein 1 and its role in extracellular vesicles-mediated intrasplenic infections</rdf:li>
   </rdf:Alt>
  </dc:title>
 </rdf:Description>

 <rdf:Description rdf:about=''
  xmlns:pdf='http://ns.adobe.com/pdf/1.3/'>
  <pdf:Keywords>Plasmodium vivax, intrasplenic infections, extracellular vesicles (EVs), CRISPR/Ca9, single-cell RNASeq (scRNASeq), spleen fibroblasts</pdf:Keywords>
 </rdf:Description>

 <rdf:Description rdf:about=''
  xmlns:xmpRights='http://ns.adobe.com/xap/1.0/rights/'>
  <xmpRights:Marked>True</xmpRights:Marked>
  <xmpRights:WebStatement>https://www.frontiersin.org/legal/copyright-statement</xmpRights:WebStatement>
 </rdf:Description>
</rdf:RDF>
</x:xmpmeta>
   Pages: 
    Page: 
     Label: 1
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 221, 685, 473, 706
      Annotation: 
       Subtype: Link
       Rect: 221, 660, 533, 681
      Annotation: 
       Subtype: Link
       Rect: 221, 635, 545, 656
      Annotation: 
       Subtype: Link
       Rect: 221, 610, 434, 631
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
      Annotation: 
       Subtype: Link
       Rect: 49, 690, 125, 705
      Annotation: 
       Subtype: Link
       Rect: 60, 537, 170, 544
      Annotation: 
       Subtype: Link
       Rect: 60, 517, 159, 524
      Annotation: 
       Subtype: Link
       Rect: 49, 317, 156, 324
      Annotation: 
       Subtype: Link
       Rect: 49, 240, 195, 247
      Annotation: 
       Subtype: Link
       Rect: 454, 802, 510, 809
      Annotation: 
       Subtype: Link
       Rect: 471, 793, 511, 800
      Annotation: 
       Subtype: Link
       Rect: 451, 783, 542, 790
      Annotation: 
       Subtype: Link
       Rect: 49, 789, 328, 806
    Page: 
     Label: 2
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 101, 681, 166, 690
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 151, 669, 285, 678
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 247, 631, 290, 640
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 49, 619, 66, 628
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 89, 606, 160, 615
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 236, 594, 290, 603
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 49, 581, 107, 590
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 155, 544, 228, 553
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 232, 544, 285, 553
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 52, 519, 97, 528
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 173, 506, 242, 515
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 90, 481, 154, 490
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 159, 481, 180, 490
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 253, 469, 290, 478
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 49, 456, 66, 465
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 52, 419, 165, 428
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 223, 344, 290, 353
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 49, 331, 68, 340
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 100, 306, 205, 315
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 195, 244, 270, 253
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 276, 244, 290, 253
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 49, 231, 124, 240
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 201, 156, 261, 165
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 239, 106, 290, 115
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 49, 94, 66, 103
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 70, 94, 151, 103
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 382, 731, 491, 740
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 442, 406, 480, 415
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 505, 269, 545, 278
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 304, 256, 342, 265
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 417, 219, 489, 228
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 3
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 86, 519, 174, 528
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 101, 494, 206, 503
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 330, 329, 424, 338
      Annotation: 
       Subtype: Link
       Rect: 348, 316, 463, 325
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 468, 316, 542, 325
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 307, 304, 366, 313
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 4
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 79, 694, 128, 703
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 52, 531, 98, 540
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 89, 456, 167, 465
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 52, 331, 128, 340
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 266, 319, 290, 328
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 49, 306, 89, 315
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 256, 219, 290, 228
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 49, 206, 90, 215
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 442, 631, 481, 640
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 307, 606, 370, 615
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 366, 331, 405, 340
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 396, 281, 497, 290
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 502, 119, 545, 128
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 304, 106, 322, 115
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 5
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 6
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 141, 706, 285, 715
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 307, 756, 414, 765
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 307, 719, 393, 728
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 308, 681, 382, 690
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 389, 681, 476, 690
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 488, 681, 545, 690
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 304, 669, 340, 678
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 505, 656, 540, 665
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 491, 606, 545, 615
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 304, 594, 341, 603
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 392, 481, 492, 490
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 486, 456, 545, 465
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 304, 444, 343, 453
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 471, 419, 507, 428
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 372, 394, 409, 403
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 365, 356, 402, 365
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 308, 219, 416, 228
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 307, 144, 343, 153
       Destination: 126
      Annotation: 
       Subtype: Link
       Rect: 488, 131, 545, 140
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 304, 119, 338, 128
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 359, 94, 394, 103
       Destination: 126
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 7
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 111, 388, 196, 397
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 132, 351, 162, 360
       Destination: 144
      Annotation: 
       Subtype: Link
       Rect: 182, 301, 266, 310
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 52, 226, 84, 235
       Destination: 144
      Annotation: 
       Subtype: Link
       Rect: 247, 126, 290, 135
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 49, 113, 66, 122
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 386, 378, 497, 387
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 491, 315, 545, 324
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 304, 303, 340, 312
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 325, 215, 361, 224
       Destination: 164
      Annotation: 
       Subtype: Link
       Rect: 339, 113, 440, 122
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 291, 517, 341, 524
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 8
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 165, 344, 260, 353
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 52, 282, 163, 291
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 53, 132, 92, 141
       Destination: 164
      Annotation: 
       Subtype: Link
       Rect: 52, 94, 91, 103
       Destination: 164
      Annotation: 
       Subtype: Link
       Rect: 506, 344, 543, 353
       Destination: 164
      Annotation: 
       Subtype: Link
       Rect: 308, 157, 406, 166
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 341, 94, 377, 103
       Destination: 164
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 9
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 147, 249, 184, 258
       Destination: 188
      Annotation: 
       Subtype: Link
       Rect: 52, 224, 87, 233
       Destination: 188
      Annotation: 
       Subtype: Link
       Rect: 231, 161, 270, 170
       Destination: 188
      Annotation: 
       Subtype: Link
       Rect: 237, 124, 290, 133
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 49, 111, 66, 120
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 101, 111, 171, 120
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 227, 111, 287, 120
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 334, 289, 370, 298
       Destination: 188
      Annotation: 
       Subtype: Link
       Rect: 516, 199, 545, 208
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 304, 186, 344, 195
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 448, 174, 513, 183
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 519, 174, 540, 183
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 427, 149, 540, 158
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 10
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 121, 267, 195, 276
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 200, 267, 285, 276
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 116, 229, 217, 238
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 201, 204, 285, 213
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 162, 179, 243, 188
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 224, 104, 288, 113
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 49, 92, 127, 101
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 432, 254, 465, 263
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 470, 254, 474, 263
       Destination: 126
      Annotation: 
       Subtype: Link
       Rect: 428, 217, 540, 226
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 419, 192, 486, 201
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 369, 154, 406, 163
       Destination: 164
      Annotation: 
       Subtype: Link
       Rect: 325, 92, 360, 101
       Destination: 164
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 11
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 123, 260, 223, 269
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 52, 185, 127, 194
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 161, 172, 275, 181
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 193, 160, 287, 169
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 52, 147, 116, 156
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 84, 85, 195, 94
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 435, 110, 487, 119
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 493, 110, 545, 119
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 304, 97, 322, 106
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 12
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 216, 719, 252, 728
       Destination: 188
      Annotation: 
       Subtype: Link
       Rect: 52, 706, 122, 715
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 126, 706, 195, 715
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 229, 706, 288, 715
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 49, 694, 104, 703
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 156, 694, 196, 703
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 236, 694, 290, 703
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 49, 681, 66, 690
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 143, 681, 233, 690
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 92, 656, 173, 665
       Destination: 227
      Annotation: 
       Subtype: Link
       Rect: 180, 656, 246, 665
       Destination: 275
      Annotation: 
       Subtype: Link
       Rect: 208, 256, 290, 265
      Annotation: 
       Subtype: Link
       Rect: 49, 244, 95, 253
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 13
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 317, 640, 545, 649
      Annotation: 
       Subtype: Link
       Rect: 304, 628, 404, 637
      Annotation: 
       Subtype: Link
       Rect: 179, 545, 285, 552
      Annotation: 
       Subtype: Link
       Rect: 266, 526, 290, 533
      Annotation: 
       Subtype: Link
       Rect: 49, 518, 106, 525
      Annotation: 
       Subtype: Link
       Rect: 62, 483, 138, 490
      Annotation: 
       Subtype: Link
       Rect: 130, 448, 224, 455
      Annotation: 
       Subtype: Link
       Rect: 223, 429, 285, 436
      Annotation: 
       Subtype: Link
       Rect: 143, 402, 201, 409
      Annotation: 
       Subtype: Link
       Rect: 190, 375, 266, 382
      Annotation: 
       Subtype: Link
       Rect: 158, 348, 260, 355
      Annotation: 
       Subtype: Link
       Rect: 266, 321, 290, 328
      Annotation: 
       Subtype: Link
       Rect: 49, 313, 125, 320
      Annotation: 
       Subtype: Link
       Rect: 106, 294, 175, 301
      Annotation: 
       Subtype: Link
       Rect: 173, 267, 251, 274
      Annotation: 
       Subtype: Link
       Rect: 102, 232, 175, 239
      Annotation: 
       Subtype: Link
       Rect: 226, 205, 272, 212
      Annotation: 
       Subtype: Link
       Rect: 182, 178, 262, 185
      Annotation: 
       Subtype: Link
       Rect: 89, 151, 146, 158
      Annotation: 
       Subtype: Link
       Rect: 82, 124, 147, 131
      Annotation: 
       Subtype: Link
       Rect: 94, 97, 160, 104
      Annotation: 
       Subtype: Link
       Rect: 170, 70, 225, 77
      Annotation: 
       Subtype: Link
       Rect: 317, 521, 394, 528
      Annotation: 
       Subtype: Link
       Rect: 443, 486, 530, 493
      Annotation: 
       Subtype: Link
       Rect: 381, 459, 449, 466
      Annotation: 
       Subtype: Link
       Rect: 488, 432, 535, 439
      Annotation: 
       Subtype: Link
       Rect: 331, 405, 420, 412
      Annotation: 
       Subtype: Link
       Rect: 443, 386, 530, 393
      Annotation: 
       Subtype: Link
       Rect: 467, 359, 545, 366
      Annotation: 
       Subtype: Link
       Rect: 462, 332, 527, 339
      Annotation: 
       Subtype: Link
       Rect: 342, 297, 420, 304
      Annotation: 
       Subtype: Link
       Rect: 499, 270, 545, 277
      Annotation: 
       Subtype: Link
       Rect: 304, 262, 339, 269
      Annotation: 
       Subtype: Link
       Rect: 355, 226, 433, 233
      Annotation: 
       Subtype: Link
       Rect: 487, 190, 545, 197
      Annotation: 
       Subtype: Link
       Rect: 304, 182, 327, 189
      Annotation: 
       Subtype: Link
       Rect: 475, 154, 536, 161
      Annotation: 
       Subtype: Link
       Rect: 428, 126, 523, 133
      Annotation: 
       Subtype: Link
       Rect: 355, 98, 442, 105
      Annotation: 
       Subtype: Link
       Rect: 388, 70, 463, 77
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 14
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 149, 734, 215, 741
      Annotation: 
       Subtype: Link
       Rect: 212, 715, 276, 722
      Annotation: 
       Subtype: Link
       Rect: 62, 680, 145, 687
      Annotation: 
       Subtype: Link
       Rect: 266, 654, 290, 661
      Annotation: 
       Subtype: Link
       Rect: 49, 646, 108, 653
      Annotation: 
       Subtype: Link
       Rect: 83, 619, 166, 626
      Annotation: 
       Subtype: Link
       Rect: 344, 734, 425, 741
      Annotation: 
       Subtype: Link
       Rect: 389, 715, 455, 722
      Annotation: 
       Subtype: Link
       Rect: 394, 695, 501, 702
      Annotation: 
       Subtype: Link
       Rect: 442, 667, 518, 674
      Annotation: 
       Subtype: Link
       Rect: 304, 647, 419, 654
      Annotation: 
       Subtype: Link
       Rect: 426, 619, 484, 626
      Annotation: 
       Subtype: Link
       Rect: 451, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 202, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
  Checksum: 959647b0
   Type: CRC32
  Checksum: 3bf84e594f37d79055b7ca5fafe3464d
   Type: MD5
  Checksum: f572194461b17477704a25f42e76b71a49ef9f50
   Type: SHA-1
  Checksum: f584a791391fa8f44e09f3f5797b5014ce605595d55cd5f260655c475858d648
   Type: SHA-256