1,720,958 research outputs found

    Cells and force transduction

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    This thesis studies mechanism involved in propagating force generated at cadherin complexes. The first part of this thesis demonstrates that mechanotransduction at classical cadherin complexes is not only ligand-dependent but also dependent on the respective receptor tyrosine kinase (RTK) binding partner of cadherin. This involvement of RTKs at cadherin complexes is important in propagating force transduction globally, implying that force transduction at cadherin complexes is not restricted to cell-cell junctions but is also propagated globally via the mediation of its respective RTK binding partner. These results suggest that homophilic ligation in trans- and cadherin association with cognate receptor tyrosine kinase in cis comprises a combinatorial, mechano-chemical switch. That is, specific combinations of cadherin, ligand, and RTK is required for force-activated RTK-dependent signaling, activation of cell contractility, and cytoskeletal remodeling at perturbed cadherin adhesions. These findings confirm that cadherins form both homophilic and heterophilic bonds, but homophilic cadherin ligation selectively triggers cadherin-associated RTK signals that mechanically reinforce homophilic, but not heterophilic cadherin adhesions, thereby stabilizing homophilic adhesions and amplifying binding differences. This study demonstrates that this mechano-chemical switch is not governed by cadherin adhesion differences, but requires a specific combination of cadherin ligand in trans- and RTK expression in cis to actuate force transduction signaling on rigid surfaces to propagate force transduction at a global level. For the second part of this study used novel, force-limited nanoscale tension gauges to investigate how force and substrate stiffness guide cellular decision-making during initial cell attachment and spreading on deformable substrates. The well-established dependence of cell traction and spreading on substrate stiffness has been attributed to levels of force exerted on molecular components in focal contacts. The molecular tension gauges used in this study enabled direct estimates of the threshold, pico Newton forces that instructed decision-making at different stages of cell attachment, spreading, and adhesion maturation. These results further confirm that the force thresholds controlling adhesion and spreading transitions depend on substrate stiffness. Reported findings agree semi-quantitatively with a proposed model that attributes rigidity-dependent differences in cell spreading to stiffness-dependent rates of competing biochemical processesSubmission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-12-01The student, Zainab Rahil, accepted the attached license on 2018-11-08 at 12:34.The student, Zainab Rahil, submitted this Dissertation for approval on 2018-11-08 at 12:48.This Dissertation was approved for publication on 2018-11-13 at 10:27.DSpace SAF Submission Ingestion Package generated from Vireo submission #13072 on 2019-02-08 at 11:38:31Made available in DSpace on 2019-02-08T18:39:44Z (GMT). No. of bitstreams: 2 RAHIL-DISSERTATION-2018.pdf: 3234037 bytes, checksum: 9102145baa27ea66fe911b2de7d27c97 (MD5) LICENSE.txt: 4209 bytes, checksum: 622797e70f0705e54a9e1cb225ae76bf (MD5) Previous issue date: 2018-11-13Embargo set by: Seth Robbins for item 109931 Lift date: 2021-02-08T18:40:00Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 109931 Lift date: 2021-02-08T18:42:23Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 109931 Lift date: 2021-02-08T18:43:54Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 109931 Lift date: 2021-02-08T18:44:50Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 109931 on 2021-02-09T10:15:38Z

    Cellular decision making at the nanoscale

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    The well-established dependence of cell traction forces on the compliance of supporting matrices has been attributed to levels of force exerted on components in focal contacts. Here, use of novel, force-limited nanoscale tension gauges revealed that both force and substrate deformations govern cell decision-making during initial attachment to compliant substrates. We propose a mechanical model consistent with observed behavior. Upon formation of stable cell contacts, bond tension and tether rupture govern cell attachment, spreading, and focal adhesion maturation at force levels on individual receptors predicted by prior studies.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-08-01The student, Zainab Rahil, accepted the attached license on 2016-04-27 at 06:49.The student, Zainab Rahil, submitted this Thesis for approval on 2016-04-27 at 06:55.This Thesis was approved for publication on 2016-04-29 at 14:30.DSpace SAF Submission Ingestion Package generated from Vireo submission #9538 on 2017-09-29 at 11:12:58Made available in DSpace on 2017-09-29T17:52:42Z (GMT). No. of bitstreams: 2 RAHIL-THESIS-2017.pdf: 792019 bytes, checksum: 6dac7f28d4957688dc2e637aadd83256 (MD5) LICENSE.txt: 4209 bytes, checksum: e378cedef64d2bf28af2358536217c94 (MD5) Previous issue date: 2016-04-29Embargo set by: Colleen Fallaw for item 103531 Lift date: 2019-09-29T17:52:45Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 103531 on 2019-09-30T09:15:23Z

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Cells and force transduction

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    This thesis studies mechanism involved in propagating force generated at cadherin complexes. The first part of this thesis demonstrates that mechanotransduction at classical cadherin complexes is not only ligand-dependent but also dependent on the respective receptor tyrosine kinase (RTK) binding partner of cadherin. This involvement of RTKs at cadherin complexes is important in propagating force transduction globally, implying that force transduction at cadherin complexes is not restricted to cell-cell junctions but is also propagated globally via the mediation of its respective RTK binding partner. These results suggest that homophilic ligation in trans- and cadherin association with cognate receptor tyrosine kinase in cis comprises a combinatorial, mechano-chemical switch. That is, specific combinations of cadherin, ligand, and RTK is required for force-activated RTK-dependent signaling, activation of cell contractility, and cytoskeletal remodeling at perturbed cadherin adhesions. These findings confirm that cadherins form both homophilic and heterophilic bonds, but homophilic cadherin ligation selectively triggers cadherin-associated RTK signals that mechanically reinforce homophilic, but not heterophilic cadherin adhesions, thereby stabilizing homophilic adhesions and amplifying binding differences. This study demonstrates that this mechano-chemical switch is not governed by cadherin adhesion differences, but requires a specific combination of cadherin ligand in trans- and RTK expression in cis to actuate force transduction signaling on rigid surfaces to propagate force transduction at a global level. For the second part of this study used novel, force-limited nanoscale tension gauges to investigate how force and substrate stiffness guide cellular decision-making during initial cell attachment and spreading on deformable substrates. The well-established dependence of cell traction and spreading on substrate stiffness has been attributed to levels of force exerted on molecular components in focal contacts. The molecular tension gauges used in this study enabled direct estimates of the threshold, pico Newton forces that instructed decision-making at different stages of cell attachment, spreading, and adhesion maturation. These results further confirm that the force thresholds controlling adhesion and spreading transitions depend on substrate stiffness. Reported findings agree semi-quantitatively with a proposed model that attributes rigidity-dependent differences in cell spreading to stiffness-dependent rates of competing biochemical processesLimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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