0f458c655ee59ec6c2b943c56140ff1c  PlaPhy_a2023v191n3p1934iENG.pdf
e5d9a7367ad4680217db30582e7f61c5edc9d0b2  PlaPhy_a2023v191n3p1934iENG.pdf
8c34e7332485a24b65cc39eb8eb16f638eb902639b759f308eaf740bd8785eb3  PlaPhy_a2023v191n3p1934iENG.pdf

Title:          A mini-TGA protein modulates gene expression through heterogeneous association with transcription factors
Subject:        DOI: 10.1093/plphys/kiac579; Plant Physiology, 191, 3, 2022-12-15.; Abstract: TGA (TGACG-binding) transcription factors, which bind their target DNA through a conserved basic region leucine zipper (bZIP) domain, are vital regulators of gene expression in salicylic acid (SA)-mediated plant immunity. Here, we investigated the role of StTGA2.1, a potato (Solanum tuberosum) TGA lacking the full bZIP, which we named a mini-TGA. Such truncated proteins have been widely assigned as loss-of-function mutants. We, however, confirmed that StTGA2.1 overexpression compensates for SA-deficiency, indicating a distinct mechanism of action compared with model plant species. To understand the underlying mechanisms, we showed that StTGA2.1 can physically interact with StTGA2.2 and StTGA2.3, while its interaction with DNA was not detected. We investigated the changes in transcriptional regulation due to StTGA2.1 overexpression, identifying direct and indirect target genes. Using in planta transactivation assays, we confirmed that StTGA2.1 interacts with StTGA2.3 to activate StPRX07, a member of class III peroxidases (StPRX), which are known to play role in immune response. Finally, via structural modeling and molecular dynamics simulations, we hypothesized that the compact molecular architecture of StTGA2.1 distorts DNA conformation upon heterodimer binding to enable transcriptional activation. This study demonstrates how protein truncation can lead to distinct functions and that such events should be studied carefully in other protein families.
Keywords:       
Author:         Špela Tomaž
Creator:        Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64
Producer:       PDFlib+PDI 9.0.7p3 (C++/Win64); modified using iTextSharp 4.1.6 by 1T3XT
CreationDate:   Tue Mar 14 05:37:46 2023 CET
ModDate:        Fri May 26 14:08:07 2023 CEST
Tagged:         yes
UserProperties: no
Suspects:       no
Form:           AcroForm
JavaScript:     no
Pages:          19
Encrypted:      no
Page size:      595.276 x 782.362 pts
Page rot:       0
File size:      1409897 bytes
Optimized:      no
PDF version:    1.6


name                                 type              encoding         emb sub uni object ID
------------------------------------ ----------------- ---------------- --- --- --- ---------
XAAXOI+CronosPro-Italic              Type 1C           Custom           yes yes yes     48  0
LCSQKK+CronosPro-Bold                Type 1C           Custom           yes yes yes     49  0
OURIGI+CronosPro-Regular             Type 1C           Custom           yes yes yes     50  0
GEQBTM+CronosPro-SemiboldIt          Type 1C           Custom           yes yes yes     51  0
XXMSZP+CronosPro-Semibold            Type 1C           Custom           yes yes yes     52  0
RHQOOD+ArialMT                       TrueType          WinAnsi          yes yes no       1  0
UYHPZF+STIXGeneral-Regular           Type 1C           Custom           yes yes yes     47  0
HUKTBK+TimesNewRomanPS-ItalicMT      CID TrueType      Identity-H       yes yes yes     56  0
LHBJHW+TimesNewRomanPSMT             CID TrueType      Identity-H       yes yes yes     68  0
WFYEZB+STIXGeneral-Bold              Type 1C           Custom           yes yes yes     73  0
NTZVFN+TimesNewRomanPS-BoldMT        CID TrueType      Identity-H       yes yes yes    106  0


Jhove (Rel. 1.22.1, 2019-04-17)
 Date: 2023-05-27 02:35:16 CEST
 RepresentationInformation: PlaPhy_a2023v191n3p1934iENG.pdf
  ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17)
  LastModified: 2023-05-26 14:12:40 CEST
  Size: 1409897
  Format: PDF
  Version: 1.6
  Status: Well-Formed and valid
  SignatureMatches:
   PDF-hul
  MIMEtype: application/pdf
  Profile: Tagged PDF
  PDFMetadata: 
   Objects: 1902
   FreeObjects: 1
   IncrementalUpdates: 0
   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: A mini-TGA protein modulates gene expression through heterogeneous association with transcription factors
      Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71
      Children: 
       Item: 
        Title: Introduction
        Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2
       Item: 
        Title: Results
        Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9
        Children: 
         Item: 
          Title: Potato encodes clade II TGAs with truncated bZIP domain
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f
         Item: 
          Title: StTGA2.1 improves immune response in SA-deficient potato
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78
         Item: 
          Title: StTGA2.1 retains its dimerization ability and shows a distinct localization pattern
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee
         Item: 
          Title: Identification of potential StTGA2.1 targets with spatial transcriptomic profiling
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f
         Item: 
          Title: StTGA2.1 and StTGA2.3 activate the class III peroxidase StPRX07
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1
         Item: 
          Title: StTGA2.1 N terminus likely contributes to protein interactions and alters TGA binding to DNA
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d
       Item: 
        Title: Discussion
        Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89
       Item: 
        Title: Materials and methods
        Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9
        Children: 
         Item: 
          Title: In silico sequence and structural analysis
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e
         Item: 
          Title: MD simulations
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b
         Item: 
          Title: Plant material
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b
         Item: 
          Title: DNA constructs
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31
         Item: 
          Title: Transient expression assays
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@b7dd107
         Item: 
          Title: Confocal microscopy
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@42eca56e
         Item: 
          Title: Yeast two-hybrid assay
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@52f759d7
         Item: 
          Title: Coimmunoprecipitation assay
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7cbd213e
         Item: 
          Title: Generation of StTGA2.1 overexpression plants
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@192d3247
         Item: 
          Title: Virus inoculation and plant treatments
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3ecd23d9
         Item: 
          Title: Gene expression analysis with RT-qPCR
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@569cfc36
         Item: 
          Title: RNA sequencing analysis
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@43bd930a
         Item: 
          Title: Targeted genomic sequencing
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@33723e30
         Item: 
          Title: Transactivation assay
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@64f6106c
         Item: 
          Title: Protein production, purification, characterization, and antibody preparation
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@553a3d88
         Item: 
          Title: Surface plasmon resonance
          Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a30d1e6
       Item: 
        Title: Accession numbers
        Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5891e32e
       Item: 
        Title: Supplemental data
        Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@cb0ed20
       Item: 
        Title: Acknowledgments
        Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8e24743
       Item: 
        Title: Funding
        Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74a10858
       Item: 
        Title: References
        Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@23fe1d71
   Info: 
    Title: A mini-TGA protein modulates gene expression through heterogeneous association with transcription factors
    Author: Špela Tomaž
    Subject: DOI: 10.1093/plphys/kiac579; Plant Physiology, 191, 3, 2022-12-15.; Abstract: TGA (TGACG-binding) transcription factors, which bind their target DNA through a conserved basic region leucine zipper (bZIP) domain, are vital regulators of gene expression in salicylic acid (SA)-mediated plant immunity. Here, we investigated the role of StTGA2.1, a potato (Solanum tuberosum) TGA lacking the full bZIP, which we named a mini-TGA. Such truncated proteins have been widely assigned as loss-of-function mutants. We, however, confirmed that StTGA2.1 overexpression compensates for SA-deficiency, indicating a distinct mechanism of action compared with model plant species. To understand the underlying mechanisms, we showed that StTGA2.1 can physically interact with StTGA2.2 and StTGA2.3, while its interaction with DNA was not detected. We investigated the changes in transcriptional regulation due to StTGA2.1 overexpression, identifying direct and indirect target genes. Using in planta transactivation assays, we confirmed that StTGA2.1 interacts with StTGA2.3 to activate StPRX07, a member of class III peroxidases (StPRX), which are known to play role in immune response. Finally, via structural modeling and molecular dynamics simulations, we hypothesized that the compact molecular architecture of StTGA2.1 distorts DNA conformation upon heterodimer binding to enable transcriptional activation. This study demonstrates how protein truncation can lead to distinct functions and that such events should be studied carefully in other protein families.
    Keywords: 
    Creator: Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64
    Producer: PDFlib+PDI 9.0.7p3 (C++/Win64); modified using iTextSharp 4.1.6 by 1T3XT
    CreationDate: Tue Mar 14 06:07:46 CET 2023
    ModDate: Fri May 26 14:08:07 CEST 2023
   ID: 0x53ecd2001b48c11dac15dcf30d9985bc, 0xcdbce509d6e2e9ed5e327c32722e1214
   Filters: 
    FilterPipeline: FlateDecode
    FilterPipeline: DCTDecode
   Images: 
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1413
      ImageHeight: 180
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1266
      ImageHeight: 1383
      ColorSpace: RGB
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1266
      ImageHeight: 813
      ColorSpace: RGB
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1233
      ImageHeight: 1303
      ColorSpace: RGB
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1266
      ImageHeight: 909
      ColorSpace: RGB
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1266
      ImageHeight: 930
      ColorSpace: RGB
      BitsPerSample: 8
      BitsPerSampleUnit: integer
   Fonts: 
    Type0: 
     Font: 
      BaseFont: LHBJHW+TimesNewRomanPSMT
      Encoding: Identity-H
      ToUnicode: true
     Font: 
      BaseFont: HUKTBK+TimesNewRomanPS-ItalicMT
      Encoding: Identity-H
      ToUnicode: true
     Font: 
      BaseFont: NTZVFN+TimesNewRomanPS-BoldMT
      Encoding: Identity-H
      ToUnicode: true
    Type1: 
     Font: 
      BaseFont: XAAXOI+CronosPro-Italic
      FontSubset: true
      FirstChar: 1
      LastChar: 58
      FontDescriptor: 
       FontName: XAAXOI+CronosPro-Italic
       Flags: Nonsymbolic, Italic
       FontBBox: -191, -281, 1129, 880
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: LCSQKK+CronosPro-Bold
      FontSubset: true
      FirstChar: 1
      LastChar: 83
      FontDescriptor: 
       FontName: LCSQKK+CronosPro-Bold
       Flags: Nonsymbolic, ForceBold
       FontBBox: -187, -295, 1137, 885
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: OURIGI+CronosPro-Regular
      FontSubset: true
      FirstChar: 1
      LastChar: 100
      FontDescriptor: 
       FontName: OURIGI+CronosPro-Regular
       Flags: Nonsymbolic
       FontBBox: -179, -270, 1129, 886
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: GEQBTM+CronosPro-SemiboldIt
      FontSubset: true
      FirstChar: 1
      LastChar: 18
      FontDescriptor: 
       FontName: GEQBTM+CronosPro-SemiboldIt
       Flags: Nonsymbolic, Italic
       FontBBox: -190, -303, 1135, 884
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: XXMSZP+CronosPro-Semibold
      FontSubset: true
      FirstChar: 1
      LastChar: 75
      FontDescriptor: 
       FontName: XXMSZP+CronosPro-Semibold
       Flags: Nonsymbolic
       FontBBox: -185, -287, 1135, 885
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: WFYEZB+STIXGeneral-Bold
      FontSubset: true
      FirstChar: 1
      LastChar: 1
      FontDescriptor: 
       FontName: WFYEZB+STIXGeneral-Bold
       Flags: Nonsymbolic, ForceBold
       FontBBox: -1030, -455, 2000, 1055
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: UYHPZF+STIXGeneral-Regular
      FontSubset: true
      FirstChar: 1
      LastChar: 10
      FontDescriptor: 
       FontName: UYHPZF+STIXGeneral-Regular
       Flags: Nonsymbolic
       FontBBox: -995, -455, 2000, 1055
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
    TrueType: 
     Font: 
      BaseFont: RHQOOD+ArialMT
      FontSubset: true
      FirstChar: 32
      LastChar: 121
      FontDescriptor: 
       FontName: RHQOOD+ArialMT
       Flags: Nonsymbolic
       FontBBox: -664, -324, 2000, 1039
       FontFile2: true
      Encoding: WinAnsiEncoding
    CIDFontType2: 
     Font: 
      BaseFont: NTZVFN+TimesNewRomanPS-BoldMT
      CIDSystemInfo: 
       Registry: Adobe
       Registry: Identity
       Supplement: 0
      FontDescriptor: 
       FontName: NTZVFN+TimesNewRomanPS-BoldMT
       Flags: Nonsymbolic, ForceBold
       FontBBox: -558, -328, 2000, 1056
       FontFile2: true
     Font: 
      BaseFont: LHBJHW+TimesNewRomanPSMT
      CIDSystemInfo: 
       Registry: Adobe
       Registry: Identity
       Supplement: 0
      FontDescriptor: 
       FontName: LHBJHW+TimesNewRomanPSMT
       Flags: Nonsymbolic
       FontBBox: -568, -307, 2046, 1040
       FontFile2: true
     Font: 
      BaseFont: HUKTBK+TimesNewRomanPS-ItalicMT
      CIDSystemInfo: 
       Registry: Adobe
       Registry: Identity
       Supplement: 0
      FontDescriptor: 
       FontName: HUKTBK+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 5.4-c006 80.159825, 2016/09/16-03:31:08        ">
   <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:0256d765-fb7f-4ec9-b6af-65c6278e64da</xmpMM:InstanceID>
         <xmpMM:DocumentID>uuid:FA2C4CCB-02A9-FCB5-5575-F1EB25C8BFB9</xmpMM:DocumentID>
         <xmpRights:Marked>True</xmpRights:Marked>
         <pdf:Producer>PDFlib+PDI 9.0.7p3 (C++/Win64); modified using iTextSharp 4.1.6 by 1T3XT</pdf:Producer>
         <pdf:Keywords />
         <dc:format>application/pdf</dc:format>
         <dc:identifier>10.1093/plphys/kiac579</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">A mini-TGA protein modulates gene expression through heterogeneous association with transcription factors</rdf:li>
            </rdf:Alt>
         </dc:title>
         <dc:creator>
            <rdf:Seq>
               <rdf:li>Špela Tomaž</rdf:li>
               <rdf:li>Marko Petek</rdf:li>
               <rdf:li>Tjaša Lukan</rdf:li>
               <rdf:li>Karmen Pogačar</rdf:li>
               <rdf:li>Katja Stare</rdf:li>
               <rdf:li>Erica Teixeira Prates</rdf:li>
               <rdf:li>Daniel A. Jacobson</rdf:li>
               <rdf:li>Jan Zrimec</rdf:li>
               <rdf:li>Gregor Bajc</rdf:li>
               <rdf:li>Matej Butala</rdf:li>
               <rdf:li>Maruša Pompe Novak</rdf:li>
               <rdf:li>Quentin Dudley</rdf:li>
               <rdf:li>Nicola Patron</rdf:li>
               <rdf:li>Ajda Taler-Verčič</rdf:li>
               <rdf:li>Aleksandra Usenik</rdf:li>
               <rdf:li>Dušan Turk</rdf:li>
               <rdf:li>Salomé Prat</rdf:li>
               <rdf:li>Anna Coll</rdf:li>
               <rdf:li>Kristina Gruden</rdf:li>
            </rdf:Seq>
         </dc:creator>
         <dc:description>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">DOI: 10.1093/plphys/kiac579; Plant Physiology, 191, 3, 2022-12-15.; Abstract: TGA (TGACG-binding) transcription factors, which bind their target DNA through a conserved basic region leucine zipper (bZIP) domain, are vital regulators of gene expression in salicylic acid (SA)-mediated plant immunity. Here, we investigated the role of StTGA2.1, a potato (Solanum tuberosum) TGA lacking the full bZIP, which we named a mini-TGA. Such truncated proteins have been widely assigned as loss-of-function mutants. We, however, confirmed that StTGA2.1 overexpression compensates for SA-deficiency, indicating a distinct mechanism of action compared with model plant species. To understand the underlying mechanisms, we showed that StTGA2.1 can physically interact with StTGA2.2 and StTGA2.3, while its interaction with DNA was not detected. We investigated the changes in transcriptional regulation due to StTGA2.1 overexpression, identifying direct and indirect target genes. Using in planta transactivation assays, we confirmed that StTGA2.1 interacts with StTGA2.3 to activate StPRX07, a member of class III peroxidases (StPRX), which are known to play role in immune response. Finally, via structural modeling and molecular dynamics simulations, we hypothesized that the compact molecular architecture of StTGA2.1 distorts DNA conformation upon heterodimer binding to enable transcriptional activation. This study demonstrates how protein truncation can lead to distinct functions and that such events should be studied carefully in other protein families.</rdf:li>
            </rdf:Alt>
         </dc:description>
         <dc:rights>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">© The Author(s) 2022. Published by Oxford University Press on behalf of American Society of Plant Biologists.</rdf:li>
            </rdf:Alt>
         </dc:rights>
         <prism:aggregationType>Journal</prism:aggregationType>
         <prism:publicationName>Plant Physiology</prism:publicationName>
         <prism:copyright>© The Author(s) 2022. Published by Oxford University Press on behalf of American Society of Plant Biologists.</prism:copyright>
         <prism:issn>0032-0889</prism:issn>
         <prism:elssn>1532-2548</prism:elssn>
         <prism:volume>191</prism:volume>
         <prism:number>3</prism:number>
         <prism:issueName />
         <prism:startingPage>1934</prism:startingPage>
         <prism:endingPage>1952</prism:endingPage>
         <prism:doi>10.1093/plphys/kiac579</prism:doi>
         <prism:url>https://doi.org/10.1093/plphys/kiac579</prism:url>
         <xmp:CreateDate>2023-03-14T10:07:46+05:30</xmp:CreateDate>
         <xmp:ModifyDate>2023-05-26T12:08:07+00:00</xmp:ModifyDate>
         <xmp:CreatorTool>Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64</xmp:CreatorTool>
         <xmp:MetadataDate>2023-05-26T12:08:07+00:00</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: 104, 544, 114, 554
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 204, 544, 214, 554
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 287, 544, 297, 554
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 392, 544, 402, 554
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 471, 544, 481, 554
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 140, 530, 150, 540
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 257, 530, 267, 540
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 335, 530, 345, 540
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 417, 530, 427, 540
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 505, 530, 515, 540
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 149, 516, 159, 525
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 259, 516, 269, 525
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 351, 516, 361, 525
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 461, 516, 471, 525
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 132, 502, 142, 511
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 221, 502, 231, 511
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 502, 321, 511
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 390, 502, 400, 511
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 518, 502, 528, 511
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 142, 340, 208, 349
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 129, 285, 343, 294
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 396, 285, 451, 294
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 303, 42, 415, 48
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 45, 737, 180, 745
       Flags: Print
    Page: 
     Sequence: 2
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 186, 584, 287, 594
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 128, 523, 208, 534
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 152, 487, 195, 497
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 187, 427, 261, 437
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 211, 378, 291, 389
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 298, 378, 298, 389
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 48, 366, 143, 377
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 82, 330, 154, 340
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 159, 330, 225, 340
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 51, 305, 127, 316
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 185, 257, 261, 267
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 51, 221, 138, 231
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 241, 221, 293, 231
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 48, 209, 67, 219
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 76, 172, 187, 183
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 191, 172, 274, 183
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 73, 136, 116, 147
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 267, 112, 293, 122
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 48, 100, 92, 110
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 97, 100, 172, 110
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 183, 63, 256, 74
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 261, 63, 293, 74
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 48, 51, 93, 62
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 98, 51, 188, 62
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 314, 627, 389, 638
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 393, 627, 459, 638
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 355, 591, 432, 602
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 406, 579, 482, 590
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 474, 567, 529, 578
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 334, 471, 403, 482
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 505, 471, 556, 482
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 311, 459, 330, 470
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 482, 459, 550, 470
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 349, 447, 426, 458
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 343, 435, 424, 446
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 466, 423, 509, 434
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 314, 375, 420, 386
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 526, 99, 555, 110
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 311, 87, 357, 98
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 314, 51, 445, 62
       Flags: Print
    Page: 
     Sequence: 3
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 239, 651, 284, 662
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 39, 639, 58, 650
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 63, 639, 182, 650
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 75, 615, 116, 626
       Flags: Print
       Destination: 57
      Annotation: 
       Subtype: Link
       Rect: 42, 579, 105, 590
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 109, 579, 225, 590
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 188, 567, 225, 578
       Flags: Print
       Destination: 57
      Annotation: 
       Subtype: Link
       Rect: 182, 435, 278, 446
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 177, 357, 254, 368
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 259, 357, 284, 368
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 39, 345, 84, 356
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 135, 297, 239, 308
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 169, 249, 284, 260
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 39, 237, 45, 248
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 248, 213, 282, 224
       Flags: Print
       Destination: 61
      Annotation: 
       Subtype: Link
       Rect: 39, 201, 156, 212
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 63, 177, 138, 188
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 42, 63, 81, 74
       Flags: Print
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 105, 51, 145, 62
       Flags: Print
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 152, 51, 278, 62
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 437, 687, 547, 698
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 302, 675, 325, 686
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 305, 651, 410, 662
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 305, 543, 402, 554
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 305, 483, 346, 494
       Flags: Print
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 490, 459, 547, 470
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 302, 447, 347, 458
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 305, 423, 412, 434
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 378, 387, 417, 398
       Flags: Print
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 421, 387, 518, 398
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 416, 279, 524, 290
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 396, 255, 469, 266
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 432, 219, 541, 230
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 384, 183, 484, 194
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 490, 159, 547, 170
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 302, 147, 336, 158
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 435, 135, 528, 146
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 492, 99, 547, 110
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 302, 87, 321, 98
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 302, 51, 339, 62
       Flags: Print
       Destination: 70
    Page: 
     Sequence: 4
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 88, 101, 119, 112
       Flags: Print
       Destination: 70
      Annotation: 
       Subtype: Link
       Rect: 477, 113, 507, 123
       Flags: Print
       Destination: 70
      Annotation: 
       Subtype: Link
       Rect: 118, 181, 178, 190
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 51, 159, 146, 168
       Flags: Print
    Page: 
     Sequence: 5
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 42, 339, 74, 350
       Flags: Print
       Destination: 70
      Annotation: 
       Subtype: Link
       Rect: 80, 339, 176, 350
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 39, 303, 134, 314
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 42, 267, 186, 278
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 151, 231, 190, 242
       Flags: Print
       Destination: 76
      Annotation: 
       Subtype: Link
       Rect: 42, 171, 80, 182
       Flags: Print
       Destination: 76
      Annotation: 
       Subtype: Link
       Rect: 42, 111, 78, 122
       Flags: Print
       Destination: 76
      Annotation: 
       Subtype: Link
       Rect: 100, 99, 137, 110
       Flags: Print
       Destination: 76
      Annotation: 
       Subtype: Link
       Rect: 42, 63, 153, 74
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 350, 291, 451, 302
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 393, 231, 486, 242
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 426, 111, 475, 122
       Flags: Print
       Destination: 76
      Annotation: 
       Subtype: Link
       Rect: 490, 111, 547, 122
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 302, 99, 346, 110
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 446, 51, 485, 62
       Flags: Print
       Destination: 76
      Annotation: 
       Subtype: Link
       Rect: 490, 51, 547, 62
       Flags: Print
    Page: 
     Sequence: 6
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 48, 89, 91, 100
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 314, 51, 391, 62
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 503, 166, 556, 175
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 48, 155, 79, 164
       Flags: Print
    Page: 
     Sequence: 7
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 42, 231, 120, 242
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 126, 231, 226, 242
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 220, 183, 284, 194
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 39, 171, 44, 182
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 78, 99, 116, 110
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 121, 99, 222, 110
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 70, 63, 146, 74
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 305, 279, 391, 290
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 399, 279, 541, 290
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 390, 183, 429, 194
       Flags: Print
       Destination: 76
      Annotation: 
       Subtype: Link
       Rect: 500, 123, 545, 134
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 302, 111, 394, 122
       Flags: Print
    Page: 
     Sequence: 8
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 314, 202, 358, 212
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 314, 154, 390, 164
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 314, 82, 379, 92
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 384, 82, 503, 92
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 338, 70, 403, 80
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 189, 275, 277, 284
       Flags: Print
    Page: 
     Sequence: 9
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 247, 161, 284, 172
       Flags: Print
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 39, 149, 75, 160
       Flags: Print
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 81, 149, 180, 160
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 70, 125, 162, 136
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 286, 125, 286, 136
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 39, 113, 111, 124
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 208, 101, 279, 112
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 197, 65, 278, 76
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 329, 137, 404, 148
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 434, 113, 479, 124
       Flags: Print
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 490, 113, 547, 124
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 302, 101, 339, 112
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 424, 77, 498, 88
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 453, 53, 522, 64
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 527, 53, 547, 64
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 212, 201, 268, 210
       Flags: Print
       Destination: 111
    Page: 
     Sequence: 10
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 48, 711, 96, 722
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 51, 699, 152, 710
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 226, 699, 287, 710
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 120, 687, 198, 698
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 132, 651, 214, 662
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 160, 615, 190, 626
       Flags: Print
       Destination: 70
      Annotation: 
       Subtype: Link
       Rect: 195, 615, 293, 626
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 48, 603, 75, 614
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 240, 519, 292, 530
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 48, 507, 67, 518
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 72, 507, 164, 518
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 51, 339, 186, 350
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 254, 291, 292, 302
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 48, 279, 90, 290
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 94, 279, 168, 290
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 173, 279, 252, 290
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 51, 255, 134, 266
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 193, 219, 291, 230
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 297, 219, 297, 230
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 48, 207, 102, 218
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 108, 207, 173, 218
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 227, 183, 292, 194
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 48, 171, 98, 182
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 178, 159, 250, 170
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 220, 123, 291, 134
       Flags: Print
       Destination: 76
      Annotation: 
       Subtype: Link
       Rect: 48, 111, 148, 122
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 101, 87, 186, 98
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 149, 63, 214, 74
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 314, 711, 385, 722
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 314, 699, 403, 710
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 340, 639, 469, 650
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 314, 591, 382, 602
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 332, 555, 384, 566
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 389, 555, 472, 566
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 477, 555, 550, 566
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 488, 483, 519, 494
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 458, 243, 533, 254
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 377, 207, 489, 218
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 499, 183, 555, 194
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 171, 347, 182
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 431, 159, 517, 170
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 546, 147, 555, 158
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 311, 135, 392, 146
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 538, 135, 555, 146
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 311, 123, 358, 134
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 364, 123, 487, 134
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 462, 111, 555, 122
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 311, 99, 330, 110
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 405, 87, 489, 98
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 365, 63, 463, 74
       Flags: Print
       Destination: 109
    Page: 
     Sequence: 11
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 80, 699, 152, 710
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 123, 687, 187, 698
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 213, 675, 280, 686
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 42, 651, 140, 662
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 233, 627, 284, 638
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 39, 615, 96, 626
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 260, 603, 284, 614
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 39, 591, 82, 602
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 126, 579, 280, 590
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 42, 567, 136, 578
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 89, 543, 155, 554
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 144, 531, 270, 542
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 179, 507, 259, 518
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 42, 375, 136, 386
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 42, 207, 107, 218
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 115, 207, 183, 218
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 120, 183, 200, 194
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 176, 123, 280, 134
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 91, 111, 158, 122
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 91, 87, 154, 98
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 79, 75, 152, 86
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 42, 63, 128, 74
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 391, 687, 469, 698
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 305, 615, 383, 626
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 423, 615, 490, 626
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 447, 543, 516, 554
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 412, 435, 515, 446
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 342, 339, 433, 350
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 338, 183, 409, 194
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 509, 147, 547, 158
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 302, 135, 335, 146
       Flags: Print
       Destination: 80
      Annotation: 
       Subtype: Link
       Rect: 517, 111, 547, 122
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 302, 99, 442, 110
       Flags: Print
    Page: 
     Sequence: 12
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 205, 711, 287, 722
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 123, 423, 200, 434
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 119, 375, 191, 386
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 51, 327, 124, 338
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 97, 291, 179, 302
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 111, 279, 184, 290
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 259, 243, 293, 254
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 48, 231, 111, 242
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 381, 699, 469, 710
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 314, 639, 413, 650
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 314, 627, 419, 638
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 475, 543, 550, 554
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 356, 519, 437, 530
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 311, 483, 415, 494
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 314, 363, 383, 374
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 314, 183, 388, 194
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 478, 171, 552, 182
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 432, 111, 506, 122
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 413, 51, 453, 62
       Flags: Print
       Destination: 65
    Page: 
     Sequence: 13
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 39, 687, 170, 698
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 198, 351, 279, 362
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 42, 99, 117, 110
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 42, 75, 143, 86
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 403, 711, 474, 722
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 305, 663, 404, 674
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 499, 597, 547, 608
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 302, 585, 321, 596
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 420, 585, 492, 596
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 438, 573, 514, 584
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 467, 459, 541, 470
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 444, 303, 543, 314
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 305, 291, 379, 302
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 377, 135, 444, 146
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 305, 75, 371, 86
       Flags: Print
       Destination: 111
    Page: 
     Sequence: 14
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 194, 699, 291, 710
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 185, 651, 251, 662
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 115, 627, 185, 638
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 181, 543, 257, 554
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 197, 483, 287, 494
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 255, 435, 293, 446
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 48, 423, 67, 434
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 167, 411, 235, 422
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 95, 387, 151, 398
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 136, 375, 208, 386
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 82, 363, 170, 374
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 130, 339, 202, 350
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 110, 255, 248, 266
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 188, 243, 289, 254
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 51, 183, 128, 194
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 51, 111, 166, 122
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 177, 111, 287, 122
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 462, 699, 533, 710
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 352, 663, 436, 674
       Flags: Print
       Destination: 113
      Annotation: 
       Subtype: Link
       Rect: 404, 639, 479, 650
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 314, 627, 347, 638
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 388, 615, 480, 626
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 343, 502, 417, 512
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 323, 466, 412, 476
       Flags: Print
       Destination: 111
      Annotation: 
       Subtype: Link
       Rect: 389, 303, 493, 314
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 466, 279, 521, 290
       Flags: Print
       Destination: 113
    Page: 
     Sequence: 15
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 255, 627, 284, 638
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 39, 615, 81, 626
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 82, 591, 157, 602
       Flags: Print
       Destination: 109
      Annotation: 
       Subtype: Link
       Rect: 133, 399, 231, 410
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 250, 339, 284, 350
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 39, 327, 86, 338
       Flags: Print
       Destination: 103
      Annotation: 
       Subtype: Link
       Rect: 311, 435, 414, 446
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 411, 411, 422
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 387, 420, 398
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 351, 417, 362
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 327, 413, 338
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 303, 416, 314
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 279, 413, 290
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 255, 415, 266
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 219, 413, 230
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 195, 418, 206
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 171, 410, 182
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 147, 409, 158
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 123, 413, 134
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 87, 411, 98
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 63, 408, 74
       Flags: Print
    Page: 
     Sequence: 16
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 57, 687, 156, 698
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 57, 663, 157, 674
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 57, 639, 167, 650
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 57, 603, 167, 614
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 57, 567, 183, 578
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 57, 531, 160, 542
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 57, 507, 164, 518
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 57, 483, 162, 494
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 57, 459, 163, 470
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 416, 687, 555, 698
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 311, 675, 385, 686
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 400, 482, 555, 491
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 319, 472, 370, 481
       Flags: Print
    Page: 
     Sequence: 17
    Page: 
     Sequence: 18
    Page: 
     Sequence: 19
  Checksum: 8bb97412
   Type: CRC32
  Checksum: 0f458c655ee59ec6c2b943c56140ff1c
   Type: MD5
  Checksum: e5d9a7367ad4680217db30582e7f61c5edc9d0b2
   Type: SHA-1