Inferring the Forces Controlling Metaphase Kinetochore Oscillations by Reverse Engineering System Dynamics
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Inferring the Forces Controlling Metaphase Kinetochore Oscillations by Reverse Engineering System Dynamics", "type"=>"journal", "authors"=>[{"first_name"=>"Jonathan W.", "last_name"=>"Armond", "scopus_author_id"=>"36463216100"}, {"first_name"=>"Edward F.", "last_name"=>"Harry", "scopus_author_id"=>"47461109500"}, {"first_name"=>"Andrew D.", "last_name"=>"McAinsh", "scopus_author_id"=>"6602476937"}, {"first_name"=>"Nigel J.", "last_name"=>"Burroughs", "scopus_author_id"=>"6603705509"}], "year"=>2015, "source"=>"PLoS Computational Biology", "identifiers"=>{"pmid"=>"26618929", "doi"=>"10.1371/journal.pcbi.1004607", "pui"=>"607184100", "issn"=>"15537358", "sgr"=>"84949214063", "scopus"=>"2-s2.0-84949214063"}, "id"=>"aec133c8-f900-3ed2-a541-dbe1998f63cb", "abstract"=>"Kinetochores are multi-protein complexes that mediate the physical coupling of sister chro- matids to spindle microtubule bundles (called kinetochore (K)-fibres) from respective poles. These kinetochore-attached K-fibres generate pushing and pulling forces, which combine with polar ejection forces (PEF) and elastic inter-sister chromatin to govern chromosome movements. Classic experiments in meiotic cells using calibrated micro-needles measured an approximate stall force for a chromosome, but methods that allow the systematic deter- mination of forces acting on a kinetochore in living cells are lacking. Here we report the development of mathematical models that can be fitted (reverse engineered) to high-resolu- tion kinetochore tracking data, thereby estimating the model parameters and allowing us to indirectly compute the (relative) force components (K-fibre, spring force and PEF) acting on individual sister kinetochores in vivo.We applied our methodology to thousands of human kinetochore pair trajectories and report distinct signatures in temporal force profiles during directional switches. We found the K-fibre force to be the dominant force throughout oscilla- tions, and the centromeric spring the smallest although it has the strongest directional switching signature. There is also structure throughout the metaphase plate, with a steeper PEF potential well towards the periphery and a concomitant reduction in plate thickness and oscillation amplitude. This data driven reverse engineering approach is sufficiently flexi- ble to allow fitting of more complex mechanistic models; mathematical models of kineto- chore dynamics can therefore be thoroughly tested on experimental data for the first time. Future work will now be able to map out how individual proteins contribute to kinetochore- based force generation and sensing.", "link"=>"http://www.mendeley.com/research/inferring-forces-controlling-metaphase-kinetochore-oscillations-reverse-engineering-system-dynamics", "reader_count"=>20, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>6, "Student > Master"=>2, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>6, "Student > Master"=>2, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Mathematics"=>1, "Agricultural and Biological Sciences"=>10, "Physics and Astronomy"=>1, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Mathematics"=>{"Mathematics"=>1}}, "reader_count_by_country"=>{"Japan"=>1, "United Kingdom"=>2}, "group_count"=>2}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84949214063"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84949214063?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84949214063&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84949214063&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84949214063", "dc:identifier"=>"SCOPUS_ID:84949214063", "eid"=>"2-s2.0-84949214063", "dc:title"=>"Inferring the Forces Controlling Metaphase Kinetochore Oscillations by Reverse Engineering System Dynamics", "dc:creator"=>"Armond J.", "prism:publicationName"=>"PLoS Computational Biology", "prism:issn"=>"1553734X", "prism:eIssn"=>"15537358", "prism:volume"=>"11", "prism:issueIdentifier"=>"11", "prism:pageRange"=>nil, "prism:coverDate"=>"2015-11-01", "prism:coverDisplayDate"=>"November 2015", "prism:doi"=>"10.1371/journal.pcbi.1004607", "citedby-count"=>"8", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of Warwick", "affiliation-city"=>"Coventry", "affiliation-country"=>"United Kingdom"}], "pubmed-id"=>"26618929", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e1004607", "source-id"=>"4000151810", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fploscompbiol%2Farticle%3Fid%3D10.1371%252Fjournal.pcbi.1004607", "share_count"=>1, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>1}

Counter

  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"140"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"88", "xml_views"=>"4", "html_views"=>"767"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"90"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"48"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"59"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"47"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"48"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"31"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"34"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"48"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"29"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"3", "html_views"=>"6"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"2", "html_views"=>"9"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"3"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"16"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"8"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"3", "html_views"=>"14"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"2", "year"=>"2020", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"19"}
  • {"month"=>"3", "year"=>"2020", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"22"}
  • {"month"=>"4", "year"=>"2020", "pdf_views"=>"32", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"5", "year"=>"2020", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"6", "year"=>"2020", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"7", "year"=>"2020", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"11"}
  • {"month"=>"8", "year"=>"2020", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"9", "year"=>"2020", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"10", "year"=>"2020", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"17"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2594004"], "description"=>"<p>(A) Model schematic showing the orientation of the two sisters and the respective forces (arrows). Sister kinetochores are connected by a linear spring (producing force <i>F</i><sub>spring</sub>, green) and are attached to a K-fibre in either a polymerising (<i>F</i><sub>+</sub>, blue) or depolymerising (<i>F</i><sub>−</sub>, red) state. The direction of polar ejection forces (PEF, <i>F</i><sub>PEF</sub>) is indicated by orange arrows. Sisters may be off-axis (twist angle <i>θ</i>); the spring force (and natural length) are then projected onto the metaphase plate normal. A directional switch is shown with the trailing sister (left) switching first (K-fibre catastrophe), followed by the originally leading sister (K-fibre rescue). See main text for details. (B) Simulated trajectory from model <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004607#pcbi.1004607.e020\" target=\"_blank\">Eq (5)</a> showing the (normal) distance from the metaphase plate of the two sisters. Parameters used were <i>p</i><sub><i>c</i></sub> = 0.94, <i>p</i><sub><i>ic</i></sub> = 0.61, <i>v</i><sub>+</sub> = 0.05 μm s<sup>−1</sup>, <i>v</i><sub>−</sub> = −0.03 μm s<sup>−1</sup>, <i>L</i> = 0.8 μm, <i>κ</i> = 0.05 s<sup>−1</sup>, <i>α</i> = 0.03 s<sup>−1</sup> and <i>τ</i> = 1000 s<sup>2</sup> μm<sup>−2</sup>, (Δ<i>t</i> = 2<i>s</i>). See <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004607#sec002\" target=\"_blank\">Methods</a> for parameter explanation. (C) Example sister pair trajectory, from kinetochore tracking of live-cell imaging data, showing the (normal) distance from the metaphase plate of the two sisters. (D) The hidden Markov chain transition network for K-fibres switching between polymerising (+) and depolymerising (–) states used in the MCMC algorithm model. <i>p</i><sub><i>c</i></sub>, <i>p</i><sub><i>ic</i></sub> are the probabilities of remaining coherent and incoherent, respectively, and <i>q</i><sub><i>c</i></sub> = 1−<i>p</i><sub><i>c</i></sub> and <i>q</i><sub><i>ic</i></sub> = 1−<i>p</i><sub><i>ic</i></sub>. (E) Time-lapse sequence of kinetochores. Kinetochores are marked by eGFP-CENP-A. Yellow bordered panel at right shows single kinetochore pair indicated by yellow box in first image.</p>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613934, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004607.g001", "stats"=>{"downloads"=>14, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Oscillating_stochastic_kinetochore_model_/1613934", "title"=>"Oscillating stochastic kinetochore model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-30 02:50:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2594005"], "description"=>"<p>Inferred posterior distributions and model parameters for the single trajectory shown in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004607#pcbi.1004607.g001\" target=\"_blank\">Fig 1C</a> for (A) the K-fibre (de)polymerisation velocities <i>v</i><sub>+</sub> (blue) and <i>v</i><sub>−</sub> (red); (B) spring constant <i>κ</i>; (C) anti-poleward force gradient <i>α</i>; (D) noise parameter <i>τ</i> = <i>s</i><sup>−2</sup>; (E) natural length <i>L</i>; (F) probabilities of not switching state per time-point when sisters are coherent (blue) and incoherent (red). The informed Gaussian prior for <i>L</i> determined through nocodazole treatment (see <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004607#pcbi.1004607.s002\" target=\"_blank\">S1 Fig</a>) is shown in red in (E). Posterior distributions consist of over 5,000 samples (see section 1.2 of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004607#pcbi.1004607.s001\" target=\"_blank\">S1 Text</a> for convergence protocols). (G) Trajectories for sisters of trajectory in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004607#pcbi.1004607.g001\" target=\"_blank\">Fig 1C</a> with switching points marked by dashed lines. (H) Probability of switching per frame shown for each sister. (I) Posterior probabilities of sister state over the course of the trajectory. Incoherent state –/– does not occur during this particular trajectory.</p>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613935, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004607.g002", "stats"=>{"downloads"=>5, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Posterior_distribution_from_a_trajectory_with_strong_oscillations_/1613935", "title"=>"Posterior distribution from a trajectory with strong oscillations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-30 02:50:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2594006"], "description"=>"<p>(A) Histogram of explained variance (EV) of each trajectory. (B) Explained variance of each trajectory arranged by cell. (C) Histogram of log Bayes factor of the kinetochore model <i>M</i><sub>coh</sub> against Brownian motion <i>M</i><sub>BM</sub> (log <i>B</i>[<i>M</i><sub>coh</sub>/<i>M</i><sub>BM</sub>]) of each trajectory. (D) log <i>B</i>[<i>M</i><sub>coh</sub>/<i>M</i><sub>BM</sub>] of each trajectory arranged by cell. (E) Histogram of directional correlation statistic <i>D</i><sub>Δ<i>t</i></sub> of each trajectory. (F) <i>D</i><sub>Δ<i>t</i></sub> of each trajectory arranged by cell. (G) log <i>B</i>[<i>M</i><sub>coh</sub>/<i>M</i><sub>BM</sub>] plotted against EV for each trajectory. Trajectories are coloured according to <i>D</i><sub>Δ<i>t</i></sub>; blue have significant directional correlations. (H) Mean trajectory positions within the metaphase plate viewed along the spindle axis (Y, Z) coloured by EV. All converged trajectories are shown in panels (A-G) (<i>n</i> = 1169); only those from grey area in (G) are shown in (H) (<i>n</i> = 843).</p>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613936, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004607.g003", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Determination_of_oscillatory_trajectories_using_three_quality_statistics_/1613936", "title"=>"Determination of oscillatory trajectories using three quality statistics.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-30 02:50:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2594008"], "description"=>"<p>Posterior means for (A) K-fibre (de)polymerisation velocities <i>v</i><sub>+</sub> (blue) and <i>v</i><sub>−</sub> (red); (B) spring constant <i>κ</i>; (C) anti-poleward force gradient <i>α</i>; (D) noise parameter <i>τ</i> = <i>s</i><sup>−2</sup>; (E) natural length <i>L</i> (blue); (F) the probabilities of not switching state per time-point when sisters are coherent (blue) and incoherent (red). The informed Gaussian prior on <i>L</i> is shown in red in (E). Dashed line and shaded areas in (A-F) indicate mean and ±s.d., respectively. (G-L) Trajectories binned by radial distance from the centre of metaphase plate (with approximately equal numbers per bin; alternating grey and white boxes) for parameters as in (A-F). Circles indicate mean of bin and lines show ±s.d.. All panels include all converged and filtered trajectories (<i>n</i> = 843).</p>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613938, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004607.g004", "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Population_parameter_analysis_/1613938", "title"=>"Population parameter analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-30 02:50:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2594009"], "description"=>"<p>(A) Schematic of the forces acting on kinetochore sisters. (B-E) Estimated decomposition of kinetochore velocity into its force components over time for the trajectory in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004607#pcbi.1004607.g001\" target=\"_blank\">Fig 1C</a>; (B, D) sister 1 and (C, E) sister 2. Polymerisation/depolymerisation force on kinetochores attributable to the K-fibre (blue/red, respectively); spring force (green); polar ejection forces (orange) and the total force (purple). Time-series overlaid with inferred end (black dashed) and start (green dashed) times of coherence periods (runs). Between end and start times K-fibres are incoherent (in this case +/+) Note that forces are positive in the anti-poleward direction.</p>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613939, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004607.g005", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Force_decomposition_profile_/1613939", "title"=>"Force decomposition profile.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-30 02:50:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2594011"], "description"=>"<p>(A) Example trajectory exhibiting lead initiated directional switching (LIDS; magenta dashed lines) and trail initiated directional switching (TIDS; black dashed lines). (B) Probability of the trailing vs. lead sister switching first (n = 2063 switch events). Dotted white line indicates the boundary where <i>p</i><sub>LIDS</sub> = <i>p</i><sub>TIDS</sub>.</p>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613941, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004607.g006", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lead_or_the_trailing_sister_can_initiate_directional_switching_/1613941", "title"=>"Lead or the trailing sister can initiate directional switching.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-30 02:50:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2594012"], "description"=>"<p>(A) Distributions of absolute forces (spring, PEF and K-fibre) averaged over trajectories (and sisters). (B) Mean force partition averaged over all time-points, time-points where the kinetochore is attached to a polymerising or depolymerising K-fibre. Absolute force values are averaged over respective sister and time-points across all trajectories (<i>n</i> = 843).</p>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613942, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004607.g007", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Average_force_decomposition_across_the_population_of_trajectories_/1613942", "title"=>"Average force decomposition across the population of trajectories.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-30 02:50:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2594014"], "description"=>"<p>Time-dependent estimation of (A) spring force and (B) PEF. Switch events from trajectories where the lead (LIDS, <i>n</i> = 1614; magenta) or trail (TIDS, <i>n</i> = 449; black) kinetochore switched first were aligned at their median switching time (the time origin is marked by vertical blue line). Solid lines indicate mean, dashed lines ±s.e.m.. Forces are given as velocities by rescaling by the viscosity coefficient. (C) Opposing force (spring + PEF) on lead sister during a LIDS (magenta) or TIDS (black) is plotted relative to the depolymerisation force <i>F</i><sub>−</sub>. Solid lines indicate mean, dashed lines 5% and 95% percentiles of the population. (D) Spring force heat map across switching events partitioned by difference between probability of LIDS (<i>p</i><sub>LIDS</sub>) or TIDS (<i>p</i><sub>TIDS</sub>). Events above zero on right <i>y</i>-axis are classified as LIDS; those below as TIDS.</p>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613944, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004607.g008", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Force_profiles_during_directional_switches_/1613944", "title"=>"Force profiles during directional switches.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-30 02:50:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2594015"], "description"=>"<p>(A) Average absolute PEF (on sister 1) binned by distance <i>r</i> from the centre of the metaphase plate (bins of approximately equal number; alternating grey and white boxes). (B) Average profile of the proportion of the opposing force (spring + PEF) to <i>F</i><sub>−</sub> on lead sister during a LIDS for trajectories with <i>r</i> ≥ 4 μm (cyan) and <i>r</i> ≤ 3 μm (blue). Switch events aligned as described under <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004607#pcbi.1004607.g008\" target=\"_blank\">Fig 8</a>. Solid and dashed lines indicate mean and ±s.e.m., respectively. (C-F) Trajectories binned by distance <i>r</i> as in (A) with bin mean of (C) alignment deviation; (D) oscillation amplitude; (E) metaphase plate thickness; (F) inter-sister distance shown. Lines in (D,F) indicate s.d., <i>n</i> = 843, see text for definitions.</p>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613945, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004607.g009", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PEF_variation_over_the_metaphase_plate_impacts_oscillation_amplitude_and_deviation_from_alignment_/1613945", "title"=>"PEF variation over the metaphase plate impacts oscillation amplitude and deviation from alignment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-30 02:50:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2594020", "https://ndownloader.figshare.com/files/2594021", "https://ndownloader.figshare.com/files/2594022", "https://ndownloader.figshare.com/files/2594023"], "description"=>"<div><p>Kinetochores are multi-protein complexes that mediate the physical coupling of sister chromatids to spindle microtubule bundles (called kinetochore (K)-fibres) from respective poles. These kinetochore-attached K-fibres generate pushing and pulling forces, which combine with polar ejection forces (PEF) and elastic inter-sister chromatin to govern chromosome movements. Classic experiments in meiotic cells using calibrated micro-needles measured an approximate stall force for a chromosome, but methods that allow the systematic determination of forces acting on a kinetochore in living cells are lacking. Here we report the development of mathematical models that can be fitted (reverse engineered) to high-resolution kinetochore tracking data, thereby estimating the model parameters and allowing us to indirectly compute the (relative) force components (K-fibre, spring force and PEF) acting on individual sister kinetochores in vivo. We applied our methodology to thousands of human kinetochore pair trajectories and report distinct signatures in temporal force profiles during directional switches. We found the K-fibre force to be the dominant force throughout oscillations, and the centromeric spring the smallest although it has the strongest directional switching signature. There is also structure throughout the metaphase plate, with a steeper PEF potential well towards the periphery and a concomitant reduction in plate thickness and oscillation amplitude. This data driven reverse engineering approach is sufficiently flexible to allow fitting of more complex mechanistic models; mathematical models of kinetochore dynamics can therefore be thoroughly tested on experimental data for the first time. Future work will now be able to map out how individual proteins contribute to kinetochore-based force generation and sensing.</p></div>", "links"=>[], "tags"=>["oscillation amplitude", "sister kinetochores", "ejection forces", "plate thickness", "Classic experiments", "force profiles", "meiotic cells", "force components", "spindle microtubule bundles", "model parameters", "sister chromatids", "chromosome movements", "pef", "Engineering System Dynamics Kinetochores", "kinetochore dynamics", "spring force", "future work", "engineering approach", "stall force", "centromeric spring", "metaphase plate", "kinetochore pair trajectories", "Forces Controlling Metaphase Kinetochore Oscillations"], "article_id"=>1613950, "categories"=>["Uncategorised"], "users"=>["Jonathan W. Armond", "Edward F. Harry", "Andrew D. McAinsh", "Nigel J. Burroughs"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1004607.s001", "https://dx.doi.org/10.1371/journal.pcbi.1004607.s002", "https://dx.doi.org/10.1371/journal.pcbi.1004607.s003", "https://dx.doi.org/10.1371/journal.pcbi.1004607.s004"], "stats"=>{"downloads"=>6, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inferring_the_Forces_Controlling_Metaphase_Kinetochore_Oscillations_by_Reverse_Engineering_System_Dynamics_/1613950", "title"=>"Inferring the Forces Controlling Metaphase Kinetochore Oscillations by Reverse Engineering System Dynamics", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-11-30 02:50:56"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"18", "full-text"=>"13", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"4", "full-text"=>"7", "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"=>"9", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"5", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"0", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"3", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"6", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"1", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"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"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"3", "full-text"=>"1", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"3", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"2", "full-text"=>"0", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
Loading … Spinner
There are currently no alerts