Lentiviral Gene Transfer of Rpe65 Rescues Survival and Function of Cones in a Mouse Model of Leber Congenital Amaurosis
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Lentiviral gene transfer of Rpe65 rescues survival and function of cones in a mouse model of leber congenital amaurosis", "type"=>"journal", "authors"=>[{"first_name"=>"Alexis Pierre", "last_name"=>"Bemelmans", "scopus_author_id"=>"6508250081"}, {"first_name"=>"Corinne", "last_name"=>"Kostic", "scopus_author_id"=>"7801364817"}, {"first_name"=>"Sylvain V.", "last_name"=>"Crippa", "scopus_author_id"=>"8626254500"}, {"first_name"=>"William W.", "last_name"=>"Hauswirth", "scopus_author_id"=>"7005825295"}, {"first_name"=>"Janis", "last_name"=>"Lem", "scopus_author_id"=>"6701618698"}, {"first_name"=>"Francis L.", "last_name"=>"Munier", "scopus_author_id"=>"7007024528"}, {"first_name"=>"Mathias W.", "last_name"=>"Seeliger", "scopus_author_id"=>"7004132922"}, {"first_name"=>"Andreas", "last_name"=>"Wenzel", "scopus_author_id"=>"7102489631"}, {"first_name"=>"Yvan", "last_name"=>"Arsenijevic", "scopus_author_id"=>"6701838564"}], "year"=>2006, "source"=>"PLoS Medicine", "identifiers"=>{"scopus"=>"2-s2.0-33750855742", "pmid"=>"17032058", "sgr"=>"33750855742", "doi"=>"10.1371/journal.pmed.0030347", "isbn"=>"1549-1676 (Electronic)\\r1549-1277 (Linking)", "issn"=>"15491277", "pui"=>"44721828"}, "id"=>"0037700d-a948-3de2-b983-5406158b5308", "abstract"=>"BACKGROUND RPE65 is specifically expressed in the retinal pigment epithelium and is essential for the recycling of 11-cis-retinal, the chromophore of rod and cone opsins. In humans, mutations in RPE65 lead to Leber congenital amaurosis or early-onset retinal dystrophy, a severe form of retinitis pigmentosa. The proof of feasibility of gene therapy for RPE65 deficiency has already been established in a dog model of Leber congenital amaurosis, but rescue of the cone function, although crucial for human high-acuity vision, has never been strictly proven. In Rpe65 knockout mice, photoreceptors show a drastically reduced light sensitivity and are subject to degeneration, the cone photoreceptors being lost at early stages of the disease. In the present study, we address the question of whether application of a lentiviral vector expressing the Rpe65 mouse cDNA prevents cone degeneration and restores cone function in Rpe65 knockout mice. METHODS AND FINDINGS Subretinal injection of the vector in Rpe65-deficient mice led to sustained expression of Rpe65 in the retinal pigment epithelium. Electroretinogram recordings showed that Rpe65 gene transfer restored retinal function to a near-normal pattern. We performed histological analyses using cone-specific markers and demonstrated that Rpe65 gene transfer completely prevented cone degeneration until at least four months, an age at which almost all cones have degenerated in the untreated Rpe65-deficient mouse. We established an algorithm that allows prediction of the cone-rescue area as a function of transgene expression, which should be a useful tool for future clinical trials. Finally, in mice deficient for both RPE65 and rod transducin, Rpe65 gene transfer restored cone function when applied at an early stage of the disease. CONCLUSIONS By demonstrating that lentivirus-mediated Rpe65 gene transfer protects and restores the function of cones in the Rpe65(-/-) mouse, this study reinforces the therapeutic value of gene therapy for RPE65 deficiencies, suggests a cone-preserving treatment for the retina, and evaluates a potentially effective viral vector for this purpose.", "link"=>"http://www.mendeley.com/research/lentiviral-gene-transfer-rpe65-rescues-survival-function-cones-mouse-model-leber-congenital-amaurosi", "reader_count"=>38, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>12, "Agricultural and Biological Sciences"=>15, "Neuroscience"=>3, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Neuroscience"=>{"Neuroscience"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>3}

CrossRef

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/33750855742"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/33750855742?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33750855742&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=33750855742&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/33750855742", "dc:identifier"=>"SCOPUS_ID:33750855742", "eid"=>"2-s2.0-33750855742", "dc:title"=>"Lentiviral gene transfer of Rpe65 rescues survival and function of cones in a mouse model of leber congenital amaurosis", "dc:creator"=>"Bemelmans A.", "prism:publicationName"=>"PLoS Medicine", "prism:issn"=>"15491277", "prism:eIssn"=>"15491676", "prism:volume"=>"3", "prism:issueIdentifier"=>"10", "prism:pageRange"=>"1892-1903", "prism:coverDate"=>"2006-10-01", "prism:coverDisplayDate"=>"October 2006", "prism:doi"=>"10.1371/journal.pmed.0030347", "citedby-count"=>"85", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Jules Gonin Eye Hospital", "affiliation-city"=>"Lausanne", "affiliation-country"=>"Switzerland"}], "pubmed-id"=>"17032058", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "source-id"=>"144840", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosmedicine%2Farticle%3Fid%3D10.1371%252Fjournal.pmed.0030347", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"10", "year"=>"2006", "pdf_views"=>"104", "xml_views"=>"1", "html_views"=>"273"}
  • {"month"=>"11", "year"=>"2006", "pdf_views"=>"93", "xml_views"=>"0", "html_views"=>"190"}
  • {"month"=>"12", "year"=>"2006", "pdf_views"=>"20", "xml_views"=>"2", "html_views"=>"54"}
  • {"month"=>"1", "year"=>"2007", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"2", "year"=>"2007", "pdf_views"=>"17", "xml_views"=>"3", "html_views"=>"36"}
  • {"month"=>"3", "year"=>"2007", "pdf_views"=>"26", "xml_views"=>"1", "html_views"=>"39"}
  • {"month"=>"4", "year"=>"2007", "pdf_views"=>"16", "xml_views"=>"4", "html_views"=>"29"}
  • {"month"=>"5", "year"=>"2007", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"6", "year"=>"2007", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"7", "year"=>"2007", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"45"}
  • {"month"=>"8", "year"=>"2007", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"9", "year"=>"2007", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"10", "year"=>"2007", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"24"}
  • {"month"=>"11", "year"=>"2007", "pdf_views"=>"20", "xml_views"=>"2", "html_views"=>"35"}
  • {"month"=>"12", "year"=>"2007", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"1", "year"=>"2008", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"35"}
  • {"month"=>"2", "year"=>"2008", "pdf_views"=>"6", "xml_views"=>"4", "html_views"=>"25"}
  • {"month"=>"3", "year"=>"2008", "pdf_views"=>"9", "xml_views"=>"7", "html_views"=>"31"}
  • {"month"=>"4", "year"=>"2008", "pdf_views"=>"18", "xml_views"=>"2", "html_views"=>"43"}
  • {"month"=>"5", "year"=>"2008", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"6", "year"=>"2008", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"7", "year"=>"2008", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"8", "year"=>"2008", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"9", "year"=>"2008", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"10", "year"=>"2008", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"11", "year"=>"2008", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"12", "year"=>"2008", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"1", "year"=>"2009", "pdf_views"=>"9", "xml_views"=>"2", "html_views"=>"31"}
  • {"month"=>"2", "year"=>"2009", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"3", "year"=>"2009", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"4", "year"=>"2009", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"5", "year"=>"2009", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"6", "year"=>"2009", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"7", "year"=>"2009", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"8", "year"=>"2009", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"9", "year"=>"2009", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"10", "year"=>"2009", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"11", "year"=>"2009", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"12", "year"=>"2009", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"1", "year"=>"2010", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"2", "year"=>"2010", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"3", "year"=>"2010", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"4", "year"=>"2010", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"33"}
  • {"month"=>"5", "year"=>"2010", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"6", "year"=>"2010", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"7", "year"=>"2010", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"8", "year"=>"2010", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"9", "year"=>"2010", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"23"}
  • {"month"=>"10", "year"=>"2010", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"22"}
  • {"month"=>"11", "year"=>"2010", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"12", "year"=>"2010", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"1", "year"=>"2011", "pdf_views"=>"7", "xml_views"=>"2", "html_views"=>"19"}
  • {"month"=>"2", "year"=>"2011", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"3", "year"=>"2011", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"4", "year"=>"2011", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"5", "year"=>"2011", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"6", "year"=>"2011", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"7", "year"=>"2011", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"8", "year"=>"2011", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"9", "year"=>"2011", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"10", "year"=>"2011", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"11", "year"=>"2011", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"12", "year"=>"2011", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"1", "year"=>"2012", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"2", "year"=>"2012", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"3", "year"=>"2012", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"4", "year"=>"2012", "pdf_views"=>"14", "xml_views"=>"2", "html_views"=>"46"}
  • {"month"=>"5", "year"=>"2012", "pdf_views"=>"9", "xml_views"=>"2", "html_views"=>"30"}
  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"33"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"8", "xml_views"=>"6", "html_views"=>"55"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"16", "xml_views"=>"2", "html_views"=>"42"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"47"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"4", "html_views"=>"59"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"51"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"36"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"2", "html_views"=>"56"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"3", "html_views"=>"86"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"73"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"71"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"82"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"2", "xml_views"=>"3", "html_views"=>"73"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"95"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"116"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"124"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"1", "xml_views"=>"2", "html_views"=>"47"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"16"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"23"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"29"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"2", "html_views"=>"17"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"2", "html_views"=>"17"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"2", "html_views"=>"5"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"3", "html_views"=>"8"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"5", "html_views"=>"12"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"14"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"13"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"7"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/956308"], "description"=>"<div><p>(A and B) PNA linked to TRITC labels cone outer segments in red in a LV-RPE65-treated eye (A). (B) Merged picture representing RPE65 (green), PNA labelling (red), and cell nuclei (blue) in the same section used in (A).</p>\n <p>(C) PNA labelling was quantified by counting the number of PNA-positive outer segments in the sagittal section that bisected the optic nerve for each eye of LV-RPE65 (<i>n</i> = 9) or LV-GFP (<i>n</i> = 7) treated groups as well as of <i>Rpe65</i><sup>−/−</sup> (KO; <i>n</i> = 4) and wild-type control groups (<i>n</i> = 4). Values represent percentage of wild type (set to 100%). A significant increase of PNA labelling was seen for LV-RPE65 treated group compared to the LV-GFP (<i>n</i> = 7, <i>p</i> = 0.007) or untreated (<i>n</i> = 4, <i>p</i> = 0.018) groups (*<i>p</i> < 0.05). Data are presented as a mean percentage of the wild-type value ± SEM.</p>\n <p>(D) GNAT2 (revealed in green by a secondary antibody linked to FITC) in a wild-type retina.</p>\n <p>(E) The GNAT2 staining is extremely weak in <i>Rpe65</i><sup>−/−</sup> mice at age 4 mo. *Example of remaining outer segment staining counted in the <i>Rpe65</i><sup>−/−</sup> and LV-GFP treated groups.</p>\n <p>(F) Quantification of GNAT2 labelling was performed (as described for PNA labelling) and showed a significant increase of GNAT2 expression in the LV-RPE65 group (<i>n</i> = 6) compared to the LV-GFP (<i>n</i> = 8, <i>p</i> = 0.017) or untreated (<i>n</i> = 4, <i>p</i> = 0.03) groups (*<i>p</i> < 0.05). The discrepancy in cone loss between PNA and GNAT2 markers in <i>Rpe65</i><sup>−/−</sup> (compare control groups in C and F) is most probably due to the persistence of the cone interphotoreceptor matrix sheath, which can still be present after other cone markers have disappeared [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030347#pmed-0030347-b042\" target=\"_blank\">42</a>]. Data are presented as a mean percentage of the wild-type value ± SEM.</p>\n <p>(G and H) A GNAT2 pattern similar to that observed in wild-type mice is recovered after LV-RPE65 treatment in <i>Rpe65</i><sup>−/−</sup> mice (G). Double labelling shows GNAT2 stained in red, RPE65 in green (H). Example of outer segment positive for GNAT2 is pointed by an arrowhead.</p>\n <p>(I) LV-GFP treatment does not improve GNAT2 expression in <i>Rpe65</i><sup>−/−</sup>. Example of weak residual labelling for GNAT2 in a control eye treated with LV-GFP (arrow).</p>\n <p>(J) After LV-RPE65 treatment, a transitional area with spared GNAT2-positive cones but devoid of RPE65 expression was observed (dashed line).</p>\n <p>(K and L) In (K) the diagram depicts a transitional area in a ring (red) surrounding the transduced area (green). The radius of the transduced area is indicated by x; the width of the transitional area is indicated by y. The relation of x to y is graphed in (L); the radius of the transduced area is linearly correlated with the transitional area.</p>\n <p>Scale bar in (I): 50 μm in A, B, E, and G–I; 100 μm in D and J. KO, <i>Rpe65</i><sup>−/−</sup> mice; LV-GFP, LV-GFP-treated mice; LV-RPE65, LV-RPE65-treated mice; WT, <i>Rpe65</i><sup>+</sup><sup>/</sup><sup>+</sup> mice.</p></div>", "links"=>[], "tags"=>["gnat2", "labelling", "lv-rpe65", "p5"], "article_id"=>626578, "categories"=>["Neuroscience", "Genetics", "Medicine"], "users"=>["Alexis-Pierre Bemelmans", "Corinne Kostic", "Sylvain V Crippa", "William W Hauswirth", "Janis Lem", "Francis L Munier", "Mathias W Seeliger", "Andreas Wenzel", "Yvan Arsenijevic"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030347.g003", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PNA_and_GNAT2_Labelling_Increase_after_LV_RPE65_Treatment_at_P5_of_Rpe65_8722_8722_Mice_/626578", "title"=>"PNA and GNAT2 Labelling Increase after LV-RPE65 Treatment at P5 of <i>Rpe65</i><sup>−/−</sup> Mice", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:12:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/956548"], "description"=>"<p><i>Rpe65</i><sup>−/−</sup> mice were treated by subretinal injection at age 1 mo with 20 ng of lentiviral vector. Treatment at this age with the LV-RPE65 vector restored ERG response with a threshold response of 3 × 10<sup>−</sup><sup>2</sup> cd s/m<sup>2</sup> for the b-wave (A), whereas no improvement was observed in the LV-GFP treated group (unpublished data). (B) Counting of PNA-positive and GNAT2-positive cells revealed that <i>Rpe65</i> gene transfer performed at age 1 mo was unable to protect the cones from degeneration. Data are presented as mean ± SEM.</p>", "links"=>[], "tags"=>["performed", "mo", "fails", "cone", "photoreceptors"], "article_id"=>626819, "categories"=>["Neuroscience", "Genetics", "Medicine"], "users"=>["Alexis-Pierre Bemelmans", "Corinne Kostic", "Sylvain V Crippa", "William W Hauswirth", "Janis Lem", "Francis L Munier", "Mathias W Seeliger", "Andreas Wenzel", "Yvan Arsenijevic"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030347.g005", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rpe65_Gene_Transfer_Performed_at_1_mo_Fails_to_Protect_Cone_Photoreceptors_from_Degeneration_/626819", "title"=>"<i>Rpe65</i> Gene Transfer Performed at 1 mo Fails to Protect Cone Photoreceptors from Degeneration", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:14:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/956472"], "description"=>"<div><p>(A) Double immunostaining of wild-type retina with antibodies directed against S-opsin (red) and M/L-opsin (green) localized in the outer segment. Note that some cones express both opsins while others are mainly labelled for only one of these opsins.</p>\n <p>(B–D) LV-RPE65 treatment allows similar expression of both S- and M/L-opsin to the wild-type retina in the region expressing the <i>Rpe65</i> transgene. Arrows indicate double labelling of cone opsins; arrowheads indicate cone stained only for S-opsin.</p>\n <p>(E and F) LV-GFP treatment does not rescue S- or M/L-opsin expression and shows a pattern of staining similar to untreated <i>Rpe65</i><sup>−/−</sup> (unpublished data). *Mislocalized and reduced S- and M/L-opsin expression.</p>\n <p>(G) Quantification of the three eyes with the highest transgene expression for LV-RPE65 and LV-GFP groups shows a significant increase in both S- and M/L-opsin expression after LV-RPE65 treatment compared to the LV-GFP (<i>p</i> = 0.005 for M/L-opsin and <i>p</i> < 0.0001 for S-opsin) or untreated (<i>n</i> = 4, <i>p</i> = 0.024 for M/L-opsin and <i>p</i> < 0.0001 for S-opsin) groups (*<i>p</i> < 0.05). No statistical difference was noted between LV-GFP and untreated knockout animals.</p>\n <p>Data are presented as mean ± SEM. Scale bar in (F): 500 μm in A; 50 μm in B–F. KO, <i>Rpe65</i><sup>−/−</sup> mice; LV-GFP, LV-GFP-treated mice; LV-RPE65, LV-RPE65-treated mice; WT, <i>Rpe65</i><sup>+/+</sup> mice.</p></div>", "links"=>[], "tags"=>["opsin", "labelling", "lv-rpe65", "mice"], "article_id"=>626743, "categories"=>["Neuroscience", "Genetics", "Medicine"], "users"=>["Alexis-Pierre Bemelmans", "Corinne Kostic", "Sylvain V Crippa", "William W Hauswirth", "Janis Lem", "Francis L Munier", "Mathias W Seeliger", "Andreas Wenzel", "Yvan Arsenijevic"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030347.g004", "stats"=>{"downloads"=>1, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_S_and_M_L_Cone_Opsin_Labelling_Increased_after_LV_RPE65_Treatment_of_Rpe65_8722_8722_Mice_at_P5_/626743", "title"=>"S- and M/L-Cone Opsin Labelling Increased after LV-RPE65 Treatment of <i>Rpe65</i><sup>−/−</sup> Mice at P5", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:13:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/956133"], "description"=>"<div><p><i>Rpe65</i><sup>−/−</sup> mice were treated P5 by an intravitreal injection of 20 ng of lentiviral vector.</p>\n <p>(A) ERG response to single flashes was recorded in scotopic condition at 2 mo of age. After LV-GFP treatment, the mice showed a response typical for <i>Rpe65</i><sup>−/−</sup> mice, with the a-wave absent and the b-wave elicited only for the highest stimuli (i.e., 10 and 25 cd s/m<sup>2</sup>; left tracings). After LV-RPE65 treatment, a stimulus of 10<sup>−</sup><sup>2</sup> cd s/m<sup>2</sup> was sufficient to trigger the b-wave, and the a-wave appeared for a stimulus of 0.3 cd s/m<sup>2</sup> (right tracings). Vertical bars indicate occurrence of the stimuli; x-axis: 40 ms/div; y-axis: 100 μV/div.</p>\n <p>(B) Summary of the ERG recordings performed 2 mo after vector delivery at P5 in <i>Rpe65</i><sup>−/−</sup> mice. Amplitude of b-wave (expressed in μV) is represented for each stimulus intensity. In the LV-RPE65-treated group (squares), the b-wave rose with a stimulus as low as 10<sup>−</sup><sup>2</sup> cd s/m<sup>2</sup>, whereas in the LV-GFP-treated group (triangles) 3 cd s/m<sup>2</sup> were necessary to elicit the b-wave. ANOVA for repeated measures showed significant stimulus intensity effect (<i>p</i> < 0.0001), group effect (<i>p</i> = 0.023), and group versus stimulus intensity interaction (<i>p</i> = 0.002). Data are presented as mean ± standard error of the mean (SEM).</p>\n <p>(C) Improvement of the ERG response after LV-RPE65 treatment is correlated with the level of RPE65 expression. The area of the retina expressing GFP (triangles) or RPE65 (squares) was quantified for each eye at age 4 mo after gene transfer at P5, and plotted against the b-wave threshold (defined as the intensity of the lowest stimulus capable of eliciting the b-wave, expressed in log mcd s/m<sup>2</sup>).</p></div>", "links"=>[], "tags"=>["lv-rpe65", "vector", "restores", "erg"], "article_id"=>626409, "categories"=>["Neuroscience", "Genetics", "Medicine"], "users"=>["Alexis-Pierre Bemelmans", "Corinne Kostic", "Sylvain V Crippa", "William W Hauswirth", "Janis Lem", "Francis L Munier", "Mathias W Seeliger", "Andreas Wenzel", "Yvan Arsenijevic"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030347.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_LV_RPE65_Vector_Restores_the_ERG_Response_of_the_Rpe65_8722_8722_Mice_/626409", "title"=>"The LV-RPE65 Vector Restores the ERG Response of the <i>Rpe65</i><sup>−/−</sup> Mice", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:10:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/956007"], "description"=>"<p><i>Rpe65</i><sup>−/−</sup> mice received the LV-GFP vector (A–D) or the LV-RPE65 vector (F and G) as an intravitreal injection at P5 (A, D–G) or a subretinal injection at 1 mo of age (B and C). 1 wk later GFP expression in the RPE was detected spanning a large proportion of the retina (A and B). Although to a lesser extent, transduced cells were also evident in the photoreceptor layer after injection at P5 (D). GFP expression was detected in the ONL (arrowheads in D) as well as in the outer segments (arrows in D). (E) DAPI counterstaining of the sample in (D). GFP was also detected occasionally in Müller cells after injection in the subretinal space at the age of 1 mo (C). After injection of the LV-RPE65 vector, immunolabelling showed RPE65 expression in the RPE (F and G). (H and I) Control RPE65 immunolabelling on noninjected <i>Rpe65</i><sup>−/−</sup> retina (G) and wild-type retina (H). Scale bar in (I): 100 μm in A, B, and G–I; 25 μm in C–F.</p>", "links"=>[], "tags"=>["lentiviral", "backbone", "containing", "promoter", "efficiently", "expresses", "transgene"], "article_id"=>626268, "categories"=>["Neuroscience", "Genetics", "Medicine"], "users"=>["Alexis-Pierre Bemelmans", "Corinne Kostic", "Sylvain V Crippa", "William W Hauswirth", "Janis Lem", "Francis L Munier", "Mathias W Seeliger", "Andreas Wenzel", "Yvan Arsenijevic"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030347.g001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Lentiviral_Backbone_Containing_the_R0_8_Promoter_Fragment_Efficiently_Expresses_a_Transgene_in_the_Mouse_RPE_/626268", "title"=>"The Lentiviral Backbone Containing the R0.8 Promoter Fragment Efficiently Expresses a Transgene in the Mouse RPE", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:09:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/956602"], "description"=>"<div><p>(A) Scotopic ERG recorded at age 1 mo of a <i>Rpe65</i><sup>−/−</sup> mouse treated at P5 with 180 ng of LV-RPE65 (left tracings) and of a <i>Rpe65</i><sup>+/+</sup> untreated mouse (WT, right tracings). At this dose, LV-RPE65 treatment restored an ERG response similar to a wild-type response. For <i>Rpe65</i><sup>−/−</sup> eyes showing the best restoration (<i>n</i> = 3), thresholds of both the a-wave and the b-wave reached normal levels with, respectively, 10−<sup>1</sup> and 10−<sup>3</sup> cd s/m<sup>2</sup>.</p>\n <p>(B and C) At P5 <i>Rpe65</i><sup>−/−</sup>/<i>Gnat1a</i><sup>−/−</sup> mice received a bilateral intravitreal injection of the vector (LV-RPE65 or LV-GFP) at a dose of 180 ng of p24 capsid protein. 1 mo later, the ERG was recorded in scotopic (B) and in photopic conditions (C). Vertical bars indicate occurrence of the stimuli; x-axis: 40 ms/div; y-axis: 100 μV/div (left tracings), except right tracings in (A) (200 μV/div).</p></div>", "links"=>[], "tags"=>["lv-rpe65", "vector", "restores", "erg", "mice", "rescues", "cone", "photoreceptors"], "article_id"=>626873, "categories"=>["Neuroscience", "Genetics", "Medicine"], "users"=>["Alexis-Pierre Bemelmans", "Corinne Kostic", "Sylvain V Crippa", "William W Hauswirth", "Janis Lem", "Francis L Munier", "Mathias W Seeliger", "Andreas Wenzel", "Yvan Arsenijevic"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030347.g006", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_High_Dose_of_LV_RPE65_Vector_Restores_a_Near_Normal_ERG_Response_in_Rpe65_8722_8722_Mice_and_Rescues_the_Activity_of_Cone_Photoreceptors_in_Rpe65_8722_8722_Gnat1a_8722_8722_Mice_/626873", "title"=>"High Dose of LV-RPE65 Vector Restores a “Near Normal” ERG Response in <i>Rpe65</i><sup>−/−</sup> Mice and Rescues the Activity of Cone Photoreceptors in <i>Rpe65</i><sup>−/−</sup>/<i>Gnat1a</i><sup>−/−</sup> Mice", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:14:56"}

PMC Usage Stats | Further Information

  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"26", "unique-ip"=>"23", "pdf"=>"13", "year"=>"2010", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"18", "year"=>"2010", "pdf"=>"11", "unique-ip"=>"20", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"15", "unique-ip"=>"17", "pdf"=>"8", "year"=>"2010", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"13", "year"=>"2010", "pdf"=>"14", "unique-ip"=>"16", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"16", "unique-ip"=>"19", "pdf"=>"9", "year"=>"2010", "figure"=>"12", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"10", "year"=>"2010", "pdf"=>"5", "unique-ip"=>"9", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"7", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"15", "unique-ip"=>"17", "pdf"=>"9", "year"=>"2010", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"8", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"11", "year"=>"2010", "pdf"=>"3", "unique-ip"=>"12", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"11", "unique-ip"=>"18", "pdf"=>"7", "year"=>"2010", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"6", "full-text"=>"9", "year"=>"2010", "pdf"=>"2", "unique-ip"=>"17", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"16", "unique-ip"=>"15", "pdf"=>"10", "year"=>"2010", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"9", "year"=>"2010", "pdf"=>"1", "unique-ip"=>"9", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"13", "unique-ip"=>"13", "pdf"=>"7", "year"=>"2011", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"5", "year"=>"2011", "pdf"=>"1", "unique-ip"=>"8", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"11", "unique-ip"=>"15", "pdf"=>"4", "year"=>"2011", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"22", "year"=>"2011", "pdf"=>"9", "unique-ip"=>"18", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"7", "unique-ip"=>"12", "pdf"=>"3", "year"=>"2011", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"10", "year"=>"2011", "pdf"=>"7", "unique-ip"=>"14", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"7", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"11", "unique-ip"=>"9", "pdf"=>"4", "year"=>"2011", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"8", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"24", "year"=>"2011", "pdf"=>"0", "unique-ip"=>"24", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"14", "unique-ip"=>"12", "pdf"=>"4", "year"=>"2011", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"15", "year"=>"2011", "pdf"=>"3", "unique-ip"=>"15", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"10", "unique-ip"=>"12", "pdf"=>"7", "year"=>"2011", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"14", "year"=>"2011", "pdf"=>"5", "unique-ip"=>"8", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"1", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"27", "year"=>"2012", "pdf"=>"7", "unique-ip"=>"18", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"2", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"20", "unique-ip"=>"15", "pdf"=>"8", "year"=>"2012", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"3", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"12", "year"=>"2012", "pdf"=>"7", "unique-ip"=>"11", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"4", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"11", "unique-ip"=>"10", "pdf"=>"2", "year"=>"2012", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"7", "year"=>"2012", "pdf"=>"6", "unique-ip"=>"9", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"54", "month"=>"10", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"3", "unique-ip"=>"16", "pdf"=>"0", "year"=>"2006", "figure"=>"153", "scanned-summary"=>"80", "supp-data"=>"73"}
  • {"month"=>"11", "scanned-page-browse"=>"52", "cited-by"=>"1", "abstract"=>"0", "full-text"=>"3", "year"=>"2006", "pdf"=>"0", "unique-ip"=>"10", "figure"=>"145", "scanned-summary"=>"80", "supp-data"=>"71"}
  • {"scanned-page-browse"=>"23", "month"=>"12", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "unique-ip"=>"3", "pdf"=>"0", "year"=>"2006", "figure"=>"67", "scanned-summary"=>"41", "supp-data"=>"34"}
  • {"month"=>"1", "scanned-page-browse"=>"38", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"2", "year"=>"2007", "pdf"=>"0", "unique-ip"=>"23", "figure"=>"133", "scanned-summary"=>"70", "supp-data"=>"56"}
  • {"scanned-page-browse"=>"23", "month"=>"2", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"1", "unique-ip"=>"7", "pdf"=>"0", "year"=>"2007", "figure"=>"79", "scanned-summary"=>"48", "supp-data"=>"41"}
  • {"month"=>"3", "scanned-page-browse"=>"28", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "year"=>"2007", "pdf"=>"0", "unique-ip"=>"3", "figure"=>"82", "scanned-summary"=>"51", "supp-data"=>"46"}
  • {"scanned-page-browse"=>"21", "month"=>"4", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"2", "unique-ip"=>"17", "pdf"=>"0", "year"=>"2007", "figure"=>"88", "scanned-summary"=>"48", "supp-data"=>"56"}
  • {"month"=>"5", "scanned-page-browse"=>"18", "cited-by"=>"1", "abstract"=>"0", "full-text"=>"1", "year"=>"2007", "pdf"=>"0", "unique-ip"=>"10", "figure"=>"82", "scanned-summary"=>"53", "supp-data"=>"45"}
  • {"scanned-page-browse"=>"19", "month"=>"6", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"1", "unique-ip"=>"5", "pdf"=>"0", "year"=>"2007", "figure"=>"71", "scanned-summary"=>"46", "supp-data"=>"39"}
  • {"month"=>"7", "scanned-page-browse"=>"16", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "year"=>"2007", "pdf"=>"0", "unique-ip"=>"2", "figure"=>"67", "scanned-summary"=>"49", "supp-data"=>"41"}
  • {"scanned-page-browse"=>"11", "month"=>"8", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"1", "unique-ip"=>"0", "pdf"=>"0", "year"=>"2007", "figure"=>"36", "scanned-summary"=>"24", "supp-data"=>"26"}
  • {"month"=>"9", "scanned-page-browse"=>"14", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "year"=>"2007", "pdf"=>"0", "unique-ip"=>"7", "figure"=>"56", "scanned-summary"=>"35", "supp-data"=>"33"}
  • {"scanned-page-browse"=>"15", "month"=>"10", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "unique-ip"=>"6", "pdf"=>"0", "year"=>"2007", "figure"=>"65", "scanned-summary"=>"44", "supp-data"=>"33"}
  • {"month"=>"11", "scanned-page-browse"=>"25", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "year"=>"2007", "pdf"=>"0", "unique-ip"=>"8", "figure"=>"88", "scanned-summary"=>"55", "supp-data"=>"40"}
  • {"scanned-page-browse"=>"12", "month"=>"12", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "unique-ip"=>"8", "pdf"=>"0", "year"=>"2007", "figure"=>"50", "scanned-summary"=>"30", "supp-data"=>"27"}
  • {"month"=>"1", "scanned-page-browse"=>"8", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "year"=>"2008", "pdf"=>"0", "unique-ip"=>"2", "figure"=>"36", "scanned-summary"=>"26", "supp-data"=>"24"}
  • {"scanned-page-browse"=>"10", "month"=>"2", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "unique-ip"=>"1", "pdf"=>"0", "year"=>"2008", "figure"=>"45", "scanned-summary"=>"34", "supp-data"=>"33"}
  • {"month"=>"3", "scanned-page-browse"=>"17", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "year"=>"2008", "pdf"=>"0", "unique-ip"=>"2", "figure"=>"52", "scanned-summary"=>"33", "supp-data"=>"32"}
  • {"scanned-page-browse"=>"14", "month"=>"4", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"2", "unique-ip"=>"7", "pdf"=>"0", "year"=>"2008", "figure"=>"57", "scanned-summary"=>"32", "supp-data"=>"31"}
  • {"month"=>"5", "scanned-page-browse"=>"20", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "year"=>"2008", "pdf"=>"0", "unique-ip"=>"1", "figure"=>"66", "scanned-summary"=>"45", "supp-data"=>"32"}
  • {"scanned-page-browse"=>"8", "month"=>"6", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"0", "unique-ip"=>"0", "pdf"=>"0", "year"=>"2008", "figure"=>"17", "scanned-summary"=>"9", "supp-data"=>"10"}
  • {"month"=>"7", "scanned-page-browse"=>"14", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"5", "year"=>"2008", "pdf"=>"0", "unique-ip"=>"4", "figure"=>"45", "scanned-summary"=>"22", "supp-data"=>"17"}
  • {"scanned-page-browse"=>"8", "month"=>"8", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"1", "unique-ip"=>"2", "pdf"=>"0", "year"=>"2008", "figure"=>"27", "scanned-summary"=>"16", "supp-data"=>"16"}
  • {"month"=>"9", "scanned-page-browse"=>"6", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"2", "year"=>"2008", "pdf"=>"0", "unique-ip"=>"5", "figure"=>"34", "scanned-summary"=>"21", "supp-data"=>"21"}
  • {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"39", "unique-ip"=>"30", "pdf"=>"17", "year"=>"2008", "figure"=>"14", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"44", "year"=>"2008", "pdf"=>"17", "unique-ip"=>"38", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"22", "unique-ip"=>"21", "pdf"=>"9", "year"=>"2008", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"1", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"19", "year"=>"2009", "pdf"=>"13", "unique-ip"=>"23", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"2", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"21", "unique-ip"=>"22", "pdf"=>"13", "year"=>"2009", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"3", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"26", "year"=>"2009", "pdf"=>"12", "unique-ip"=>"27", "figure"=>"10", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"4", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"26", "unique-ip"=>"22", "pdf"=>"6", "year"=>"2009", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"36", "year"=>"2009", "pdf"=>"13", "unique-ip"=>"25", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"15", "unique-ip"=>"16", "pdf"=>"6", "year"=>"2009", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"7", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"6", "full-text"=>"18", "year"=>"2009", "pdf"=>"12", "unique-ip"=>"16", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"8", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"9", "unique-ip"=>"13", "pdf"=>"5", "year"=>"2009", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"9", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"9", "year"=>"2009", "pdf"=>"5", "unique-ip"=>"9", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"7", "unique-ip"=>"5", "pdf"=>"5", "year"=>"2009", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"19", "year"=>"2009", "pdf"=>"9", "unique-ip"=>"21", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"24", "unique-ip"=>"21", "pdf"=>"7", "year"=>"2009", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"11", "year"=>"2012", "pdf"=>"5", "unique-ip"=>"12", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"13", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"19", "full-text"=>"19", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"21", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"12", "full-text"=>"24", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"1", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"12", "full-text"=>"7", "pdf"=>"4", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"18", "full-text"=>"21", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"13", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"4", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"15", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"10", "full-text"=>"5", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"2", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

{"start_date"=>"2006-01-01T00:00:00Z", "end_date"=>"2006-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[297, 950, 1258, 1471, 1611, 1717, 1818, 1905, 1988, 2074, 2148, 2220, 2272, 2329, 2392, 2437, 2475, 2527, 2606, 2656, 2729, 2792, 2864, 2922, 2984, 3036, 3093, 3147, 3215, 3295, 3385, 3458, 3534, 3586, 3651, 3691, 3739, 3774, 3838, 3892, 3953, 4006, 4091, 4153, 4218, 4284, 4348, 4394, 4439, 4497, 4540, 4599, 4643, 4697, 4742, 4798, 4847, 4887, 4933, 4983, 5015, 5043, 5088, 5131, 5194, 5251, 5314, 5377, 5424, 5478, 5550, 5625, 5702, 5758, 5841, 5921, 6038, 6102, 6190, 6288, 6368, 6475, 6557, 6601, 6685, 6762, 6861, 6903, 7017, 7075, 7132, 7198, 7314, 7361, 7426, 7532, 7554]}, {"subject_area"=>"/Biology and life sciences/Anatomy and physiology", "average_usage"=>[299, 882, 1102, 1256, 1370, 1487, 1570, 1636, 1705, 1787, 1892, 1975, 2072, 2120, 2169, 2211, 2244, 2293, 2359, 2410, 2449, 2508, 2554, 2600, 2632, 2711, 2754, 2816, 2902, 3009, 3057, 3109, 3174, 3228, 3267, 3313, 3345, 3389, 3455, 3511, 3550, 3582, 3614, 3684, 3744, 3837, 3896, 3935, 3975, 4036, 4076, 4153, 4184, 4246, 4281, 4320, 4372, 4415, 4459, 4488, 4534, 4568, 4613, 4641, 4670, 4701, 4753, 4769, 4806, 4829, 4880, 4968, 5050, 5109, 5238, 5363, 5473, 5549, 5574, 5614, 5684, 5821, 5913, 5945]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[226, 741, 959, 1170, 1290, 1381, 1458, 1540, 1602, 1672, 1741, 1791, 1844, 1890, 1948, 2012, 2062, 2096, 2146, 2199, 2246, 2290, 2339, 2396, 2460, 2497, 2551, 2624, 2690, 2769, 2823, 2867, 2896, 2950, 3001, 3036, 3078, 3121, 3166, 3225, 3282, 3327, 3377, 3420, 3501, 3569, 3611, 3659, 3705, 3749, 3798, 3881, 3922, 3952, 4000, 4070, 4098, 4128, 4157, 4200, 4264, 4307, 4340, 4369, 4406, 4438, 4457, 4498, 4546, 4610, 4665, 4703, 4756, 4806, 4859, 4993, 5103, 5179, 5229, 5302, 5384, 5452, 5546, 5619, 5675, 5772, 5891, 6000, 6069, 6127, 6162, 6219, 6256, 6338, 6416, 6525, 6643]}]}
Loading … Spinner
There are currently no alerts