e6174b4f0dcf492b0e1632cf1a487d61  pmc_31267011.pdf
d485d6faccbfd8b91202de90238b38065b7fba99  pmc_31267011.pdf
baadadea0e88c026911b08c0366eb3c49eeea5391f1b3827e714097636392d44  pmc_31267011.pdf

Title:          Compensated pathogenic variants in coagulation factors VIII and IX present complex mapping between molecular impact and hemophilia severity
Subject:        Scientific Reports, doi:10.1038/s41598-019-45916-3
Keywords:       
Author:         amp#x000D2;scar Maramp#x000ED;n
Creator:        Springer
Producer:       iText® 5.3.5 ©2000-2012 1T3XT BVBA (AGPL-version)
CreationDate:   Tue Jun 25 23:35:55 2019 CEST
ModDate:        Wed Jun 26 12:34:22 2019 CEST
Tagged:         no
UserProperties: no
Suspects:       no
Form:           AcroForm
JavaScript:     no
Pages:          11
Encrypted:      no
Page size:      595.276 x 782.362 pts
Page rot:       0
File size:      2137916 bytes
Optimized:      no
PDF version:    1.4

name                                 type              encoding         emb sub uni object ID
------------------------------------ ----------------- ---------------- --- --- --- ---------
PTUZWU+Corbel-Bold                   CID TrueType      Identity-H       yes yes yes    257  0
JWOHQG+TimesNewRomanPSMT             Type 1C           WinAnsi          yes yes yes    533  0
MinionPro-Regular                    Type 1C           Custom           yes no  yes     57  0
CLOWGN+Corbel-Bold2                  Type 1C           WinAnsi          yes yes yes     58  0
MinionPro-It                         Type 1C           Custom           yes no  yes     60  0
DRCNJU+Corbel2                       Type 1C           WinAnsi          yes yes yes     61  0
KTLAEE+Corbel                        CID TrueType      Identity-H       yes yes yes     62  0
MyriadPro-It                         Type 1C           WinAnsi          yes no  yes     63  0
DRCNJU+Corbel2                       Type 1C           WinAnsi          yes yes yes    448  0
EuclidSymbol                         Type 1C           Custom           yes no  yes     56  0
MinionPro-Bold                       Type 1C           WinAnsi          yes no  yes     59  0
YZOZSC+STIXGeneral-Regular           Type 1C           Custom           yes yes yes    111  0

Jhove (Rel. 1.22.1, 2019-04-17)
 Date: 2020-08-10 12:38:43 CEST
 RepresentationInformation: pmc_31267011.pdf
  ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17)
  LastModified: 2020-03-16 03:44:16 CET
  Size: 2137916
  Format: PDF
  Version: 1.4
  Status: Well-Formed, but not valid
  SignatureMatches:
   PDF-hul
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation shown in :30' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation shown in:33' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation shown i:62' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation shown :63' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation shown:64' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), relative solven:72' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:
Table 1. Summary of the results of the statistical tests corresponding to the comparisons shown in the different figures.:73' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:
Table 1. Summary of the results of the statistical tests corresponding to the comparisons shown in the different figures.:74' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), relative solve:75' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), relat:90' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation s:91' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation sho:77' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation sh:78' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), relative sol:80' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), relative so:81' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), relative :83' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), relative:84' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), relativ:85' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 3. The molecular impact of CPDs and clinical severity. For FVIII, we plotted the value distribution of three properties (BLOSUM62 matrix elements, Shannon entropy, and ∆∆G) for the severe (black) and mild (grey) subsets. For ∆∆G, the diff:87' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 3. The molecular impact of CPDs and clinical severity. For FVIII, we plotted the value distribution of three properties (BLOSUM62 matrix elements, Shannon entropy, and ∆∆G) for the severe (black) and mild (grey) subsets. For ∆∆G, the dif:88' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 3. The molecular impact of CPDs and clinical severity. For FVIII, we plotted the value distribution of three properties (BLOSUM62 matrix elements, Shannon entropy, and ∆∆G) for the severe (black) and mild (grey) subsets. For ∆∆G, the d:93' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:
Table 1. Summary of the results of the statistical tests corresponding to the comparisons shown in the different figures.:94' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 3. The molecular impact of CPDs and clinical severity. For FVIII, we plotted the value distribution of three properties (BLOSUM62 matrix elements, Shannon entropy, and ∆∆G) for the severe (black) and mild (grey) subsets. For ∆∆G, the :95' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 3. The molecular impact of CPDs and clinical severity. For FVIII, we plotted the value distribution of three properties (BLOSUM62 matrix elements, Shannon entropy, and ∆∆G) for the severe (black) and mild (grey) subsets. For ∆∆G, th:97' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:	9.	Barešić, A., Hopcroft, L. E. M., Rogers, H. H., Hurst, J. M. & Martin, A. C. R. Compensated Pathogenic Deviations: Analysis of Structural Effects. J. Mol. Biol. 396, 19–30 (2010).
:99' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:
Table 1. Summary of the results of the statistical tests corresponding to the comparisons shown in the different figures.:100' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 4. Variability in the genetic background of FVIII and FIX. This figure shows four concrete aspects of how the sequence variants from the 1000 Genomes project are distributed across hemostasis proteins (i.e. the genetic background of FVIII:106' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 4. Variability in the genetic background of FVIII and FIX. This figure shows four concrete aspects of how the sequence variants from the 1000 Genomes project are distributed across hemostasis proteins (i.e. the genetic background of FVII:107' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 4. Variability in the genetic background of FVIII and FIX. This figure shows four concrete aspects of how the sequence variants from the 1000 Genomes project are distributed across hemostasis proteins (i.e. the genetic background of FV:109' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 5. Pathogenic load of hemostasis proteins. (A) Distribution of the number of neutral (blue) and pathogenic (red) variants per individual in the 1000 Genomes population. (B) Scatterplot showing the different combinations of neutral and:113' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 5. Pathogenic load of hemostasis proteins. (A) Distribution of the number of neutral (blue) and pathogenic (red) variants per individual in the 1000 Genomes population. (B) Scatterplot showing the different combinations of neutral an:114' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:	11.	Ferrer-Costa, C., Orozco, M. & de la Cruz, X. Characterization of Compensated Mutations in Terms of Structural and Physico-Chemical Properties. J. Mol. Biol. 365, 249–256 (2007).
:118' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), rela:124' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:	3.	DePristo, M. A., Weinreich, D. M. & Hartl, D. L. Missense meanderings in sequence space: a biophysical view of protein evolution. Nat. Rev. Genet. 6, 678–687 (2005).
:129' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), rel:130' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 3. The molecular impact of CPDs and clinical severity. For FVIII, we plotted the value distribution of three properties (BLOSUM62 matrix elements, Shannon entropy, and ∆∆G) for the severe (black) and mild (grey) subsets. For ∆∆G, t:131' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 4. Variability in the genetic background of FVIII and FIX. This figure shows four concrete aspects of how the sequence variants from the 1000 Genomes project are distributed across hemostasis proteins (i.e. the genetic background of F:132' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 3. The molecular impact of CPDs and clinical severity. For FVIII, we plotted the value distribution of three properties (BLOSUM62 matrix elements, Shannon entropy, and ∆∆G) for the severe (black) and mild (grey) subsets. For ∆∆G, :134' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 5. Pathogenic load of hemostasis proteins. (A) Distribution of the number of neutral (blue) and pathogenic (red) variants per individual in the 1000 Genomes population. (B) Scatterplot showing the different combinations of neutral :151' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 4. Variability in the genetic background of FVIII and FIX. This figure shows four concrete aspects of how the sequence variants from the 1000 Genomes project are distributed across hemostasis proteins (i.e. the genetic background of:152' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 5. Pathogenic load of hemostasis proteins. (A) Distribution of the number of neutral (blue) and pathogenic (red) variants per individual in the 1000 Genomes population. (B) Scatterplot showing the different combinations of neutral:153' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 6. Differences in the background of specific variants between FVIII and FIX. The genetic background of a given variant can vary between individuals. Here, we focus on variants of FVIII and FIX and define background as the number of accomp:154' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation :167' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 2. Differences between CPDs and noCPDs. For mutations of the two coagulation factors in our dataset, FVIII (top) and FIX (bottom), we computed the values of four properties: ∆∆G (change in protein stability upon mutation), re:168' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation:174' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:Figure 1. Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutatio:176' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:	3.	DePristo, M. A., Weinreich, D. M. & Hartl, D. L. Missense meanderings in sequence space: a biophysical view of protein evolution. Nat. Rev. Genet. 6, 678–687 (2005).
:178' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:	8.	Xu, J. & Zhang, J. Why human disease-associated residues appear as the wild-type in other species: Genome-scale structural evidence for the compensation hypothesis. Mol. Biol. Evol. 31, 1787–1792 (2014).
:180' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:	11.	Ferrer-Costa, C., Orozco, M. & de la Cruz, X. Characterization of Compensated Mutations in Terms of Structural and Physico-Chemical Properties. J. Mol. Biol. 365, 249–256 (2007).
:187' cannot be found
   Offset: 1588040
  ID: PDF-HUL-122
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_45916.indd:	19.	Pavlova, A. & Oldenburg, J. Defining severity of hemophilia: More than factor levels. Semin. Thromb. Hemost. 39, 702–710 (2013).
:193' cannot be found
   Offset: 1588040
  MIMEtype: application/pdf
  PDFMetadata: 
   Objects: 615
   FreeObjects: 1
   IncrementalUpdates: 0
   DocumentCatalog: 
    ViewerPreferences: 
     HideToolbar: false
     HideMenubar: false
     HideWindowUI: false
     FitWindow: false
     CenterWindow: false
     DisplayDocTitle: false
     NonFullScreenPageMode: UseNone
     Direction: L2R
     ViewArea: CropBox
     ViewClip: CropBox
     PrintArea: CropBox
     PageClip: CropBox
    PageLayout: SinglePage
    PageMode: UseOutlines
    Language: EN
    Outlines: 
     Item: 
      Title: Compensated pathogenic variants in coagulation factors VIII and IX present complex mapping between molecular impact and hem ...
      Children: 
       Item: 
        Title: Results
        Children: 
         Item: 
          Title: CPDs in FVIII and FIX can be associated with either mild or severe forms of hemophilia. 
         Item: 
          Title: CPDs in FVIII and FIX tend to be mild at the molecular level. 
         Item: 
          Title: The molecular impact of CPDs in FVIII (and FIX) is not strongly related to disease severity. 
         Item: 
          Title: Genetic variability in hemostasis proteins. 
       Item: 
        Title: Discussion
       Item: 
        Title: Materials and Methods
        Children: 
         Item: 
          Title: CPD dataset. 
         Item: 
          Title: Characterization of mutations in terms of molecular properties. 
         Item: 
          Title: Multiple sequence alignments. 
         Item: 
          Title: Hemostasis proteins. 
         Item: 
          Title: Variants in the 1000 Genomes project. 
       Item: 
        Title: Acknowledgements
       Item: 
        Title: Figure 1 Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity.
       Item: 
        Title: Figure 2 Differences between CPDs and noCPDs.
       Item: 
        Title: Figure 3 The molecular impact of CPDs and clinical severity.
       Item: 
        Title: Figure 4 Variability in the genetic background of FVIII and FIX.
       Item: 
        Title: Figure 5 Pathogenic load of hemostasis proteins.
       Item: 
        Title: Figure 6 Differences in the background of specific variants between FVIII and FIX.
       Item: 
        Title: Table 1 Summary of the results of the statistical tests corresponding to the comparisons shown in the different figures.
   Info: 
    Title: Compensated pathogenic variants in coagulation factors VIII and IX present complex mapping between molecular impact and hemophilia severity
    Author: amp#x000D2;scar Maramp#x000ED;n
    Subject: Scientific Reports, doi:10.1038/s41598-019-45916-3
    Keywords: 
    Creator: Springer
    Producer: iText® 5.3.5 ©2000-2012 1T3XT BVBA (AGPL-version)
    CreationDate: Wed Jun 26 00:05:55 CEST 2019
    ModDate: Wed Jun 26 12:34:22 CEST 2019
   ID: 0x59a75a7edda3c607ea56fb2c47ab7b60, 0x0441b9e89f42ce8a841519888dac26e1
   Filters: 
    FilterPipeline: FlateDecode
    FilterPipeline: DCTDecode
   Images: 
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 1100
      ImageHeight: 90
      ColorSpace: black is zero
      BitsPerSample: 1
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1650
      ImageHeight: 1158
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 1650
      ImageHeight: 1413
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 1650
      ImageHeight: 846
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 850
      ImageHeight: 866
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Name: X
   Fonts: 
    Type0: 
     Font: 
      BaseFont: PTUZWU+Corbel-Bold
      Encoding: Identity-H
      ToUnicode: true
     Font: 
      BaseFont: KTLAEE+Corbel
      Encoding: Identity-H
      ToUnicode: true
    Type1: 
     Font: 
      BaseFont: JWOHQG+TimesNewRomanPSMT
      FontSubset: true
      FirstChar: 32
      LastChar: 120
      FontDescriptor: 
       FontName: JWOHQG+TimesNewRomanPSMT
       Flags: Serif, Nonsymbolic
       FontBBox: -568, -307, 2000, 1007
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: EuclidSymbol
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: EuclidSymbol
       Flags: Symbolic
       FontBBox: -166, -253, 1090, 950
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: MinionPro-Regular
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: MinionPro-Regular
       Flags: Serif, Nonsymbolic
       FontBBox: -290, -360, 1684, 989
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: CLOWGN+Corbel-Bold2
      FontSubset: true
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: CLOWGN+Corbel-Bold2
       Flags: Nonsymbolic
       FontBBox: -556, -239, 1155, 952
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: MinionPro-Bold
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: MinionPro-Bold
       Flags: Serif, Nonsymbolic
       FontBBox: -319, -360, 1684, 1024
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: MinionPro-It
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: MinionPro-It
       Flags: Serif, Nonsymbolic, Italic
       FontBBox: -201, -360, 1684, 1002
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: DRCNJU+Corbel2
      FontSubset: true
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: DRCNJU+Corbel2
       Flags: Nonsymbolic
       FontBBox: -553, -239, 1110, 952
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: MyriadPro-It
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: MyriadPro-It
       Flags: Nonsymbolic, Italic
       FontBBox: -185, -250, 1090, 953
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: YZOZSC+STIXGeneral-Regular
      FontSubset: true
      FirstChar: 31
      LastChar: 31
      FontDescriptor: 
       FontName: YZOZSC+STIXGeneral-Regular
       Flags: Serif, Symbolic
       FontBBox: -995, -455, 2000, 1055
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
    CIDFontType2: 
     Font: 
      BaseFont: KTLAEE+Corbel
      CIDSystemInfo: 
       Registry: Adobe
       Registry: Identity
       Supplement: 0
      FontDescriptor: 
       FontName: KTLAEE+Corbel
       Flags: Symbolic
       FontBBox: -553, -239, 1110, 952
       FontFile2: true
     Font: 
      BaseFont: PTUZWU+Corbel-Bold
      CIDSystemInfo: 
       Registry: Adobe
       Registry: Identity
       Supplement: 0
      FontDescriptor: 
       FontName: PTUZWU+Corbel-Bold
       Flags: Symbolic
       FontBBox: -556, -239, 1155, 952
       FontFile2: true
   XMP: <x:xmpmeta x:xmptk="Adobe XMP Core 5.2-c001 63.143651, 2012/04/05-09:01:49        " xmlns:x="adobe:ns:meta/">
   <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:format>application/pdf</dc:format>
         <dc:identifier>doi:10.1038/s41598-019-45916-3</dc:identifier>
         <dc:publisher>
            <rdf:Bag>
               <rdf:li>Springer US</rdf:li>
            </rdf:Bag>
         </dc:publisher>
         <dc:description>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">Scientific Reports, doi:10.1038/s41598-019-45916-3</rdf:li>
            </rdf:Alt>
         </dc:description>
         <dc:title>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">Compensated pathogenic variants in coagulation factors VIII and IX present complex mapping between molecular impact and hemophilia severity</rdf:li>
            </rdf:Alt>
         </dc:title>
         <dc:creator>
            <rdf:Seq>
               <rdf:li>amp#x000D2;scar Maramp#x000ED;n</rdf:li>
               <rdf:li>Josu Aguirre</rdf:li>
               <rdf:li>Xavier de la Cruz</rdf:li>
            </rdf:Seq>
         </dc:creator>
      </rdf:Description>
      <rdf:Description rdf:about="" xmlns:prism="http://prismstandard.org/namespaces/basic/2.0/">
         <prism:doi>10.1038/s41598-019-45916-3</prism:doi>
         <prism:url>http://dx.doi.org/10.1038/s41598-019-45916-3</prism:url>
         <prism:aggregationType>journal</prism:aggregationType>
         <prism:publicationName>Scientific Reports</prism:publicationName>
         <prism:copyright>© 2019, The Author(s)</prism:copyright>
         <prism:issn>2045-2322</prism:issn>
      </rdf:Description>
      <rdf:Description rdf:about="" xmlns:pdfx="http://ns.adobe.com/pdfx/1.3/">
         <pdfx:doi>10.1038/s41598-019-45916-3</pdfx:doi>
      </rdf:Description>
      <rdf:Description rdf:about="" xmlns:xmp="http://ns.adobe.com/xap/1.0/">
         <xmp:CreatorTool>Springer</xmp:CreatorTool>
         <xmp:ModifyDate>2019-06-26T12:34:22+02:00</xmp:ModifyDate>
         <xmp:CreateDate>2019-06-26T03:05:55+05:30</xmp:CreateDate>
         <xmp:MetadataDate>2019-06-26T12:34:22+02:00</xmp:MetadataDate>
      </rdf:Description>
      <rdf:Description rdf:about="" xmlns:xmpRights="http://ns.adobe.com/xap/1.0/rights/">
         <xmpRights:Marked>True</xmpRights:Marked>
      </rdf:Description>
      <rdf:Description rdf:about="" xmlns:pdf="http://ns.adobe.com/pdf/1.3/">
         <pdf:Keywords></pdf:Keywords>
      <pdf:Producer>iText® 5.3.5 ©2000-2012 1T3XT BVBA (AGPL-version)</pdf:Producer></rdf:Description>
      <rdf:Description rdf:about="" xmlns:jav="http://www.niso.org/schemas/jav/1.0/">
         <jav:journal_article_version>VoR</jav:journal_article_version>
      </rdf:Description>
      <rdf:Description rdf:about="" xmlns:stEvt="http://ns.adobe.com/xap/1.0/sType/ResourceEvent#" xmlns:xmpMM="http://ns.adobe.com/xap/1.0/mm/">
         <xmpMM:DocumentID>uuid:a19728ba-004c-413e-9b88-4b280441a0e6</xmpMM:DocumentID>
         <xmpMM:InstanceID>uuid:88011e50-d09f-442b-9f74-e09898748578</xmpMM:InstanceID>
         <xmpMM:RenditionClass>default</xmpMM:RenditionClass>
         <xmpMM:VersionID>1</xmpMM:VersionID>
         <xmpMM:History>
            <rdf:Seq>
               <rdf:li rdf:parseType="Resource">
                  <stEvt:action>converted</stEvt:action>
                  <stEvt:instanceID>uuid:174e0d77-be24-4f33-9eb8-efcfed46f772</stEvt:instanceID>
                  <stEvt:parameters>converted to PDF/A-2b</stEvt:parameters>
                  <stEvt:softwareAgent>pdfToolbox</stEvt:softwareAgent>
                  <stEvt:when>2019-06-26T03:06:41+05:30</stEvt:when>
               </rdf:li>
            </rdf:Seq>
         </xmpMM:History>
      </rdf:Description>
      <rdf:Description rdf:about="" xmlns:pdfaid="http://www.aiim.org/pdfa/ns/id/">
         <pdfaid:part>2</pdfaid:part>
         <pdfaid:conformance>B</pdfaid:conformance>
      </rdf:Description>
      <rdf:Description rdf:about="" xmlns:pdfaExtension="http://www.aiim.org/pdfa/ns/extension/" xmlns:pdfaProperty="http://www.aiim.org/pdfa/ns/property#" xmlns:pdfaSchema="http://www.aiim.org/pdfa/ns/schema#">
         <pdfaExtension:schemas>
            <rdf:Bag>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://ns.adobe.com/pdf/1.3/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>pdf</pdfaSchema:prefix>
                  <pdfaSchema:schema>Adobe PDF Schema</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>A name object indicating whether the document has been modified to include trapping information</pdfaProperty:description>
                           <pdfaProperty:name>Trapped</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://ns.adobe.com/xap/1.0/mm/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>xmpMM</pdfaSchema:prefix>
                  <pdfaSchema:schema>XMP Media Management Schema</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>UUID based identifier for specific incarnation of a document</pdfaProperty:description>
                           <pdfaProperty:name>InstanceID</pdfaProperty:name>
                           <pdfaProperty:valueType>URI</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>The common identifier for all versions and renditions of a document.</pdfaProperty:description>
                           <pdfaProperty:name>OriginalDocumentID</pdfaProperty:name>
                           <pdfaProperty:valueType>URI</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://ns.adobe.com/pdfx/1.3/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>pdfx</pdfaSchema:prefix>
                  <pdfaSchema:schema>pdfx</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>ID of PDF/X standard</pdfaProperty:description>
                           <pdfaProperty:name>GTS_PDFXVersion</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Conformance level of PDF/X standard</pdfaProperty:description>
                           <pdfaProperty:name>GTS_PDFXConformance</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Company creating the PDF</pdfaProperty:description>
                           <pdfaProperty:name>Company</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Date when document was last modified</pdfaProperty:description>
                           <pdfaProperty:name>SourceModified</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Mirrors crossmark:DOI</pdfaProperty:description>
                           <pdfaProperty:name>doi</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://www.aiim.org/pdfa/ns/id/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>pdfaid</pdfaSchema:prefix>
                  <pdfaSchema:schema>PDF/A ID Schema</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Part of PDF/A standard</pdfaProperty:description>
                           <pdfaProperty:name>part</pdfaProperty:name>
                           <pdfaProperty:valueType>Integer</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Amendment of PDF/A standard</pdfaProperty:description>
                           <pdfaProperty:name>amd</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Conformance level of PDF/A standard</pdfaProperty:description>
                           <pdfaProperty:name>conformance</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://prismstandard.org/namespaces/basic/2.0/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>prism</pdfaSchema:prefix>
                  <pdfaSchema:schema>Prism</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>The aggregation type specifies the unit of aggregation for a content collection. 
Comment 
PRISM recommends that the PRISM Aggregation Type Controlled Vocabulary be used to provide values for this element. 
Note: PRISM recommends against the use of the #other value currently allowed in this controlled vocabulary. In lieu of using #other please reach out to the PRISM group at info@prismstandard.org to request addition of your term to the Aggregation Type Controlled Vocabulary. 

</pdfaProperty:description>
                           <pdfaProperty:name>aggregationType</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>Copyright </pdfaProperty:description>
                           <pdfaProperty:name>copyright</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>The Digital Object Identifier for the article.
The DOI may also be used as the dc:identifier. If used as a dc:identifier, the URI form should be captured, and the bare identifier should also be captured using prism:doi. If an alternate unique identifier is used as the required dc:identifier, then the DOI should be specified as a bare identifier within prism:doi only. 
If the URL associated with a DOI is to be specified, then prism:url may be used in conjunction with prism:doi in order to provide the service endpoint (i.e. the URL). 
</pdfaProperty:description>
                           <pdfaProperty:name>doi</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>ISSN for an electronic version of the issue in which the resource occurs. 
Permits publishers to include a second ISSN, identifying an electronic version of the issue in which the resource occurs (therefore e(lectronic)Issn. If used, prism:eIssn MUST contain the ISSN of the electronic version. See prism:issn. 
</pdfaProperty:description>
                           <pdfaProperty:name>issn</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>Title of the magazine, or other publication, in which a resource was/will be published. 
Typically this will be used to provide the name of the magazine an article appeared in as metadata for the article, along with information such as the article title, the publisher, volume, number, and cover date. 

Note: Publication name can be used to differentiate between a print magazine and the online version if the names are different such as “magazine” and “magazine.com.” 
</pdfaProperty:description>
                           <pdfaProperty:name>publicationName</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>This element provides the url for an article or unit of content. 
The attribute platform is optionally allowed for situations in which multiple URLs must be specified. PRISM recommends that a subset of the PCV platform values, namely “mobile” and “web”, be used in conjunction with this element. 
NOTE: PRISM recommends against the use of the #other value allowed in the PRISM Platform controlled vocabulary. In lieu of using #other please reach out to the PRISM group at prism-wg@yahoogroups.com to request addition of your term to the Platform Controlled Vocabulary. 
</pdfaProperty:description>
                           <pdfaProperty:name>url</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://www.niso.org/schemas/jav/1.0/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>jav</pdfaSchema:prefix>
                  <pdfaSchema:schema>NISO</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>Values for Journal Article Version are one of the following:
AO = Author’s Original
SMUR = Submitted Manuscript Under Review
AM = Accepted Manuscript
P = Proof
VoR = Version of Record
CVoR = Corrected Version of Record
EVoR = Enhanced Version of Record</pdfaProperty:description>
                           <pdfaProperty:name>journal_article_version</pdfaProperty:name>
                           <pdfaProperty:valueType>Closed Choice of Text</pdfaProperty:valueType>
                        </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: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 352, 478, 361, 466
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 308, 273, 311, 261
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 313, 273, 315, 261
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 417, 273, 420, 261
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 423, 273, 426, 261
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 463, 263, 466, 251
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 367, 253, 378, 241
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 413, 223, 416, 211
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 420, 213, 423, 201
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 423, 203, 433, 191
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 425, 193, 428, 181
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 513, 193, 515, 181
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 220, 183, 226, 171
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 342, 173, 348, 161
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 200, 133, 203, 121
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 181, 53, 269, 43
       Flags: Print
       AppearanceDictionary: true
     Thumb: true
    Page: 
     Sequence: 2
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 273, 295, 276, 283
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 277, 295, 283, 283
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 465, 275, 471, 263
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 307, 245, 312, 233
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 270, 215, 275, 203
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 184, 205, 190, 193
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 319, 195, 322, 183
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 323, 195, 328, 183
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 514, 165, 516, 153
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 255, 145, 258, 133
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 259, 145, 265, 133
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 265, 135, 270, 123
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 456, 135, 462, 123
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 272, 115, 278, 103
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 281, 115, 287, 103
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 323, 75, 329, 63
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 193, 65, 199, 53
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 468, 428, 473, 416
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 336, 388, 339, 376
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
     Thumb: true
    Page: 
     Sequence: 3
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 242, 390, 248, 378
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 249, 390, 255, 378
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 258, 390, 264, 378
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 236, 380, 242, 368
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 388, 322, 398, 310
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 174, 252, 185, 240
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 433, 242, 444, 230
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 274, 212, 279, 200
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 170, 174, 173, 162
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 174, 174, 180, 162
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 343, 154, 349, 142
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 327, 134, 333, 122
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 259, 124, 265, 112
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 352, 114, 357, 102
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 406, 94, 411, 82
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 500, 84, 504, 72
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 331, 65, 335, 51
       Flags: Print
       AppearanceDictionary: true
       Destination: null
     Thumb: true
    Page: 
     Sequence: 4
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 392, 168, 396, 155
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 383, 116, 387, 104
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 211, 106, 221, 94
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 419, 56, 425, 44
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 170, 723, 178, 713
       Flags: Print
       AppearanceDictionary: true
       Destination: 3
      Annotation: 
       Subtype: Link
       Rect: 170, 711, 178, 702
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 170, 700, 179, 690
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 170, 688, 174, 678
       Flags: Print
       AppearanceDictionary: true
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 170, 676, 174, 667
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 170, 665, 174, 655
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 170, 653, 174, 644
       Flags: Print
       AppearanceDictionary: true
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 170, 642, 174, 631
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 170, 630, 174, 620
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 170, 618, 174, 609
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 170, 607, 174, 597
       Flags: Print
       AppearanceDictionary: true
       Destination: 65
      Annotation: 
       Subtype: Link
       Rect: 170, 595, 174, 585
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 170, 583, 174, 574
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 170, 572, 174, 562
       Flags: Print
       AppearanceDictionary: true
       Destination: 116
     Thumb: true
    Page: 
     Sequence: 5
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 407, 684, 411, 672
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 330, 675, 334, 661
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 489, 664, 493, 652
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 195, 594, 199, 582
       Flags: Print
       AppearanceDictionary: true
       Destination: 116
      Annotation: 
       Subtype: Link
       Rect: 171, 574, 175, 562
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 303, 574, 309, 562
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 428, 564, 431, 552
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 210, 524, 214, 512
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 455, 474, 461, 462
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 404, 454, 410, 442
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 549, 454, 554, 442
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 318, 424, 324, 412
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 327, 424, 332, 412
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 194, 414, 205, 402
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 217, 384, 227, 372
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 378, 364, 389, 352
       Flags: Print
       AppearanceDictionary: true
       Destination: 258
      Annotation: 
       Subtype: Link
       Rect: 270, 344, 281, 332
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 330, 334, 336, 322
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 491, 314, 494, 302
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 528, 284, 534, 272
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 380, 274, 390, 262
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 519, 264, 528, 252
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 264, 204, 266, 192
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 268, 204, 271, 192
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 272, 204, 278, 192
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 279, 204, 285, 192
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 286, 204, 292, 192
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 344, 194, 347, 182
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 348, 194, 354, 182
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 351, 184, 354, 172
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 355, 184, 361, 172
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 382, 184, 386, 172
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 167, 164, 170, 152
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 171, 164, 174, 152
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 175, 164, 181, 152
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 182, 164, 188, 152
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 299, 164, 301, 152
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 541, 94, 546, 82
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 550, 94, 554, 82
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 497, 84, 501, 72
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 505, 84, 510, 72
       Flags: Print
       AppearanceDictionary: true
       Destination: 294
      Annotation: 
       Subtype: Link
       Rect: 203, 64, 207, 52
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 398, 55, 400, 41
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 402, 55, 407, 41
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
     Thumb: true
    Page: 
     Sequence: 6
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 535, 273, 540, 261
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 405, 263, 411, 251
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 501, 243, 507, 231
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 450, 183, 456, 170
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 457, 183, 463, 170
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 430, 143, 433, 131
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 434, 143, 440, 131
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 443, 143, 448, 131
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 357, 133, 362, 121
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 380, 113, 386, 101
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 389, 113, 394, 101
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 509, 113, 514, 101
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 473, 73, 478, 61
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
     Thumb: true
    Page: 
     Sequence: 7
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 541, 400, 551, 388
       Flags: Print
       AppearanceDictionary: true
       Destination: 258
      Annotation: 
       Subtype: Link
       Rect: 389, 390, 393, 378
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 248, 380, 252, 368
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 256, 380, 260, 368
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 503, 360, 507, 348
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 250, 350, 255, 338
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 374, 350, 380, 338
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 190, 320, 194, 308
       Flags: Print
       AppearanceDictionary: true
       Destination: 294
      Annotation: 
       Subtype: Link
       Rect: 486, 320, 491, 308
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 551, 290, 554, 278
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 544, 270, 547, 258
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 549, 270, 554, 258
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 268, 260, 273, 248
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 167, 148, 363, 136
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 366, 148, 372, 136
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 426, 148, 554, 136
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 155, 138, 228, 126
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 232, 138, 237, 126
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 478, 138, 484, 126
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 505, 128, 510, 116
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 202, 68, 213, 56
       Flags: Print
       AppearanceDictionary: true
       Destination: null
     Thumb: true
    Page: 
     Sequence: 8
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 227, 398, 231, 386
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 224, 318, 230, 306
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 508, 288, 513, 276
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 199, 278, 205, 266
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 206, 278, 211, 266
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 299, 228, 304, 216
       Flags: Print
       AppearanceDictionary: true
       Destination: 116
      Annotation: 
       Subtype: Link
       Rect: 282, 208, 293, 196
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 516, 208, 522, 196
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 336, 148, 347, 136
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 275, 67, 277, 53
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 189, 57, 192, 43
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 193, 57, 199, 43
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 349, 57, 352, 43
       Flags: Print
       AppearanceDictionary: true
       Destination: null
     Thumb: true
    Page: 
     Sequence: 9
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 231, 734, 236, 722
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 338, 714, 344, 702
       Flags: Print
       AppearanceDictionary: true
       Destination: 382
      Annotation: 
       Subtype: Link
       Rect: 501, 714, 507, 702
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 343, 704, 349, 692
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 505, 694, 510, 682
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 179, 684, 185, 672
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 376, 664, 382, 652
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 248, 644, 253, 632
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 244, 594, 250, 582
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 202, 584, 207, 572
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 529, 564, 535, 551
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 292, 544, 298, 531
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 391, 544, 397, 531
       Flags: Print
       AppearanceDictionary: true
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 460, 544, 466, 531
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 349, 514, 355, 501
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
      Annotation: 
       Subtype: Link
       Rect: 361, 463, 367, 451
       Flags: Print
       AppearanceDictionary: true
       Destination: 421
     Thumb: true
    Page: 
     Sequence: 10
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 356, 71, 515, 59
       Flags: Print
       AppearanceDictionary: true
     Thumb: true
    Page: 
     Sequence: 11
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 222, 25, 369, 16
       Flags: Print
       AppearanceDictionary: true
      Annotation: 
       Subtype: Link
       Rect: 344, 640, 504, 628
       Flags: Print
       AppearanceDictionary: true
     Thumb: true
  Checksum: 2d51e80a
   Type: CRC32
  Checksum: e6174b4f0dcf492b0e1632cf1a487d61
   Type: MD5
  Checksum: d485d6faccbfd8b91202de90238b38065b7fba99
   Type: SHA-1