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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Development of methods for high-throughput viscoelastic analysis for suspension as well as adherent cells
No full textCell mechanical properties reveal substantial information on cell state and function. Utilizing mechanics as a label-free biomarker allows for investigation of fundamental cellular processes as well as biomedical applications, e.g., disease diagnosis. High-throughput methods for accessing the elastic properties of cells in suspension from hydrodynamic deformation in a microfluidic constriction are available with real-time analysis rates of up to 1000 cells per second. However, accessing elastic as well as viscous properties of cells and multicellular systems in suspension as well as adhered to surfaces at high throughput has not been possible so far. In this thesis, I approached this question and developed as well as applied microfluidic and holographic technologies to analyze the viscoelastic properties of single cells and multicellular aggregates, respectively.
First, I demonstrated that real-time deformability cytometry (RT-DC) can be applied in transfusion medicine, where the highest quality standards have to be maintained while blood product release is time-critical. We showed for platelet and red blood cell concentrates as well as for hematopoietic stem cells that their mechanical properties can be used for label-free quality assessment. The results have been published in Lab on a Chip (Aurich et al. 2020).
For RT-DC and many other methods based on hydrodynamic deformation, the constriction size has to be adapted to the objects of interest to allow for a shear-induced deformation. We introduced virtual fluidic channels, which are established by two co-flowing aqueous polymer solutions. Virtual fluidic channels can be precisely adjusted in their cross section, allowing for mechanical phenotyping of single cells as well as cell clusters or tissue spheroids in one microfluidic system. Importantly, measurements can also be performed in standard microfluidic geometries beyond soft lithography, e.g., in the cuvette of a flow cytometer. For cell spheroids as a model system for multicellular aggregates, we show a 10-fold lower Young's modulus of the tissue compared to single-cell mechanics, suggesting cell-cell and cell-matrix interactions being potential contributors to the mechanics of multicellular aggregates. Our work on virtual fluidic channels has been published in Nature Communications (Panhwar et al. 2020).
Within this thesis, I expanded the high-throughput elastic phenotyping performed by RT-DC towards viscoelastic cell properties by developing dynamic real-time deformability cytometry (dRT-DC). Dynamic tracking of cells while passing the microfluidic constriction allows to access steady-state (elasticity) and time-dependent (viscosity) material properties for a complete viscoelastic characterization of cells in suspension at high throughput. I introduced a shape mode decomposition based on a Fourier transformation, which allows to disentangle the superimposed stress responses to an extensional stress at the channel inlet and a constant shear stress in the channel. These hydrodynamic stress distributions are present in almost every microfluidic channel geometry. From the separated stress responses, viscoelastic material properties can be determined independent of cell shape.
We demonstrated experimentally the sensitivity of dRT-DC to cytoskeletal alterations and confirmed the validity of the method by reference measurements on calibrated hydrogel beads. In our work, we also presented a viscoelastic fingerprint of the major subpopulations of peripheral blood: erythrocytes, granulocytes, and peripheral blood mononuclear cells (PBMCs) (e.g., lymphocytes and monocytes), all characterized by the same method. The technique and the results have been published in Nature Communications (Fregin et al. 2019).
In cell mechanical methods based on hydrodynamic deformation, cell shape is usually monitored while a stress is applied. For extraction of material properties as well as for studying shape dynamics, it is essential to describe cell shape yielding highest strain differences for a given microfluidic system and experimental setting. Using dRT-DC, I compared nine different shape descriptors to analyze cell deformation in an extensional as well as shear flow. A relaxation time analysis was performed on different levels of data aggregation from single cells to an ensemble scale. I demonstrated that the steady-state deformation can be predicted from stress response curves without them reaching the steady-state. This is important for cell mechanical measurements in microfluidic systems as the characteristic times are unknown in general and as the channel length is fixed. In addition, by introducing a cut-off criterion for how much of the response trace needs to be captured within the channel, the analysis time per cell can be reduced while material properties can still be extracted. Performing simulations, I compared the accuracy of relaxation times extracted from ensemble and single-cell studies under experimental conditions. Introducing a scoring system to evaluate which combinations of shape descriptors and analysis strategies provide biggest effect size, we concluded that single-cell analyses in an extensional flow are most sensitive to cytoskeletal modifications independent of shape parametrization. The manuscript was submitted to the Biophysical Journal.
Finally, I translated the fast non-contact cell mechanical probing from suspension to adherent cells. No such technology has been available and with the majority of cells being adherent, a robust label-free method for mechanophenotyping at high-throughput is required. Within this thesis, I have introduced and realized a new concept: holographic vibration spectroscopy (HVS), where adherent cells are mechanically excited on a vibrating surface while their height oscillations are measured optically. Analysis is done in an interferometric heterodyne setup by using frequency multiplexing and time-averaged holography in off-axis configuration. Based on interference images captured by a high-speed complementary metal-oxide-semiconductor (CMOS) camera, I established a mathematical model to reconstruct the vibration amplitude of adherent cells as well as their retardation phase compared to the exciting vibration. From the amplitude and phase response, viscoelastic parameters can be derived, which have to be investigated in subsequent studies.
In summary, I introduced in my work two high-throughput methods for the viscoelastic characterization of suspended as well as adherent cells while highlighting applications in tissue mechanics and transfusion medicine that are relevant not only in basic but also in translational research.Die mechanischen Eigenschaften einer Zelle enthalten substantielle Informationen ihres Zustandes und ihrer Funktion. Die Nutzung zellmechanischer Eigenschaften als markierungsfreier Biomarker ermöglicht die Untersuchung grundlegender zellulärer Prozesse sowie den Einsatz in biomedizinische Anwendungen, z. B. zur Krankheitsdiagnose. Zur Messung elastischer Eigenschaften von Zellen in Suspension existieren bereits Hochdurchsatzmethoden mit Analyseraten von bis zu 1000 Zellen pro Sekunde in Echtzeit. Diese basieren auf hydrodynamischer Verformung der Zellen in mikrofluidischen Kanälen. Allerdings war es bisher nicht möglich, sowohl die elastischen als auch die viskosen Eigenschaften von Zellen und mehrzelligen Systemen in Suspension sowie an adhärenten Zellen mit hohem Durchsatz zu quantifizieren. In dieser Dissertation habe ich diese Fragestellung adressiert und mikrofluidische als auch holographische Techniken entwickelt und angewendet, um viskoelastische Eigenschaften von Einzelzellen bzw. mehrzelligen Aggregaten zu analysieren.
Zunächst habe ich gezeigt, dass die Verformbarkeitszytometrie in Echtzeit (real-time deformability cytometry, RT-DC) in der Transfusionsmedizin angewendet werden kann, wo höchste Qualitätsstandards eingehalten werden müssen, während die Freigabe der Blutprodukte zeitkritisch ist. Wir konnten für Thrombozyten- und Erythrozytenkonzentrate sowie für hämatopoetische Stammzellen zeigen, dass deren mechanische Eigenschaften zur markierungsfreien Qualitätsbewertung herangezogen werden können. Die Ergebnisse wurden im Journal Lab on a Chip veröffentlicht (Aurich et al. 2020).
Für RT-DC und viele andere Methoden, die auf hydrodynamischer Verformung basieren, muss die Kanalgröße an die der Objekte angepasst werden, um eine Verformung durch Scherkräfte zu ermöglichen. Wir haben das Konzept der virtuellen Fluidkanäle eingeführt, welche durch zwei wässrige Polymerlösungen gebildet werden, bei dem ein Strom den anderen einhüllt. Virtuelle Fluidkanäle können in ihrem Querschnitt präzise eingestellt werden und ermöglichen die mechanische Phänotypisierung von Einzelzellen sowie Zellverbänden oder Gewebe-Sphäroiden in einem mikrofluidischen System. Eine Stärke der Methode ist, dass Messungen auch in mikrofluidischen Standardgeometrien jenseits von abgegossenen Kanälen basierend auf Lithographie durchgeführt werden können, z. B. in der Küvette eines Durchflusszytometers. Für Zell-Sphäroide als ein Modellsystem für mehrzellige Aggregate messen wir ein 10-fach niedrigeres Elastizitätsmodul des Gewebes im Vergleich zur Einzelzellmechanik, was darauf hindeutet, dass Zell-Zell- und Zell-Matrix-Wechselwirkungen potenzielle Beiträge zur Mechanik mehrzelliger Aggregate leisten. Unsere Arbeit zu virtuellen Fluidkanälen wurde in Nature Communications veröffentlicht (Panhwar et al. 2020).
Im Rahmen dieser Arbeit entwickelte ich die dynamische Verformbarkeitszytometrie in Echtzeit (dynamic real-time deformability cytometry, dRT-DC), welche die elastische Phänotypisierung von RT-DC hin zur Hochdurchsatz-Messung viskoelastischer Zelleigenschaften erweitert. Die dynamische Verfolgung von Zellen beim Passieren der mikrofluidischen Kanäle ermöglicht sowohl die Quantifizierung stationärer (Elastizität) als auch zeitabhängiger (Viskosität) Materialeigenschaften für eine vollständige, viskoelastische Charakterisierung von Suspensionszellen bei hohem Durchsatz. Ich führte eine Zerlegung in Moden der geometrischen Form basierend auf einer Fourier-Transformation ein, welche es ermöglicht, die überlagerten Dehnungsantworten auf eine Streckspannung am Kanaleingang und den konstanten Scherstress innerhalb des Kanals zu unterscheiden. Beide hydrodynamischen Stressverteilungen sind in nahezu jeder mikrofluidischen Kanalgeometrie vorhanden. Aus den separierten Stressantworten können viskoelastische Materialeigenschaften unabhängig von der Zellform bestimmt werden.
In Experimenten haben wir die Sensitivität von dRT-DC hinsichtlich Veränderungen des Zytoskellets demonstriert und die extrahierten Materialeigenschaften durch Referenzmessungen an kalibrierten Hydrogelkugeln bestätigt. In unserer Arbeit präsentieren wir zudem die viskoelastischen Eigenschaften der wichtigsten Subpopulationen des peripheren Blutes: Erythrozyten, Granulozyten und mononukleäre Blutzellen (PBMCs) (z. B. Lymphozyten und Monozyten). Die viskoelastischen Eigenschaften aller Subpopulationen wurden mit derselben Methode charakterisiert und können wie ein mechanischer Fingerabdruck interpretiert werden. Die Methode sowie die Ergebnisse wurden im Journal Nature Communications veröffentlicht (Fregin et al. 2019).
Bei zellmechanischen Verfahren, die auf hydrodynamischer Verformung basieren, wird zumeist die Form bzw. Dehnung der Zelle beobachtet, während ein Stress aufgeprägt wird. Für die Ableitung von Materialeigenschaften sowie die Untersuchung der Dynamik der Verformung ist es wichtig, die Zellform mit höchster Sensitivität bezüglich Unterschiede in deren Dehnung unter gegebenen Randbedingungen, wie dem mikrofluidischen System und der experimentellen Umgebung, zu beschreiben. Unter Verwendung von dRT-DC habe ich neun verschiedene Formparameter verglichen, um die Zellverformung sowohl unter Streckspannung als auch unter Scherstress zu analysieren. Eine Relaxationszeitanalyse wurde auf verschiedenen Ebenen der Datenaggregation von Einzelzellen bis hin zum Ensemble durchgeführt. Ich habe gezeigt, dass die stationäre Verformung aus Stressantwortkurven vorhergesagt werden kann, ohne dass sie den stationären Zustand erreichen. Dies ist für zellmechanische Messungen in mikrofluidischen Systemen von Bedeutung, da die charakteristischen Zeiten im Allgemeinen unbekannt sind und die Kanallänge festgelegt ist. Darüber hinaus kann durch die Einführung eines Kriteriums, welches garantiert, dass ein Mindestmaß der Stressantwortkurve innerhalb des Kanals aufgenommen wird, die Analysezeit pro Zelle reduziert und dennoch Materialeigenschaften extrahiert werden. In Simulationen verglich ich die Genauigkeit der Relaxationszeiten, welche aus Ensemble- und Einzelzellstudien extrahiert wurden. Durch die Einführung eines Bewertungssystems, welches einschätzt, welche Kombination aus Formparametern und Analysestrategien die größte Effektstärke bereitstellt, kamen wir zu dem Schluss, dass Einzelzellanalysen unter Streckspannung unabhängig von der Parametrisierung der Form am empfindlichsten auf Änderungen des Zytoskeletts reagieren. Das Manuskript wurde beim Biophysical Journal eingereicht.
Schließlich übertrug ich die schnelle kontaktlose zellmechanische Charakterisierung von Suspensionszellen auf adhärente Zellen. Eine solche Messtechnik war bisher nicht verfügbar. Da die Mehrheit der Zellen adhärent ist, ist eine robuste, markierungsfreie Methode zur Mechanophänotypisierung mit hohem Durchsatz von hoher Bedeutung. Im Rahmen dieser Arbeit habe ich ein neues Konzept eingeführt und implementiert: die holographische Vibrationsspektroskopie (holographic vibration spectroscopy, HVS), bei welcher adhärente Zellen auf einer vibrierenden Oberfläche mechanisch angeregt werden, während deren Oszillationen optisch gemessen werden. Die Analyse erfolgt in einem interferometrischen, heterodynen Aufbau unter Verwendung von Frequenzmultiplexing und zeitgemittelter Holographie in Off-axis-Konfiguration. Basierend auf Interferenzbildern, die von einer Hochgeschwindigkeitskamera (CMOS) aufgenommen wurden, habe ich ein mathematisches Modell erstellt, um die Schwingungsamplitude adhärenter Zellen sowie deren Phasenverzögerung gegenüber der anregenden Schwingung zu rekonstruieren. Aus dem Amplituden- und Phasengang lassen sich viskoelastische Parameter ableiten, die in Folgestudien untersucht werden müssen.
Innerhalb meiner Doktorarbeit habe ich zwei Hochdurchsatzmethoden zur viskoelastischen Charakterisierung von Suspensionszellen sowie adhärenten Zellen eingeführt und zugleich Anwendungen in der Gewebemechanik und Transfusionsmedizin aufgezeigt, die nicht nur in der Grundlagenforschung, sondern auch in der translationalen Forschung relevant sind
Variations on the Author
Get PDF“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
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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