1,720,961 research outputs found
Migration of Primary Human Lymphocytes in 3D matrices
Full text linkCytotoxic T cells protect us from viruses and tumors and move large distances within the body to find infected or transformed target cells. Their migration is an interplay of their intrinsic ability to migrate and to sense their environment and adapt to it. The composition of extracellular signals and physical contact to connective tissue fibers modulates the migration of T cells. To be able to analyze lymphocyte behavior in 3D I first developed new imaging methods in 3D environments for epifluorescence and Single Plane Illumination Microscopy (SPIM) using collagen as matrix. As a natural non-toxic substrate that is biologically active and can form sponge-like porous matrices that are homogenous and stable under physiological conditions collagen is a perfect starting point to remodel basic tissue architecture and determine basic migration parameters of lymphocytes. Using this collagen based system with a flattened matrix to avoid out of focus migration of cells (2D matrix) I could determine the basic migration parameters of primary human cytotoxic T lymphocytes (CTL) and natural killer cells (NK) in a 3D environment using epifluorescence microscopy. In 0.25 % collagen, representing normal tissue interstitial matrix, lymphocytes migrate in a random walk at average speeds ~ 5 μm min-1 (range ~ 0.6 - 18 μm min-1) and low average persistence. Bead stimulation of CTL that enriches effector and effector memory subtypes, increases average persistence while average velocity is nearly unchanged. By adding extracellular matrix (ECM) compounds the matrix can easily be modified and cell behavior can be modulated. E.g. fibronectin can modulate cell velocity and persistence while fragmented hyaluronic acid, mimicking inflammation or injury, can modulate persistence of CTL. Transferring the collagen system to selected plane illumination microscopy (SPIM) for long term imaging of large 3D volumes SPIM is highly advantageous as it reduces potential toxicity from illumination of the sample and is unraveled in acquisition speed. Additionally the high resolution and frame rate of SPIM systems allows imaging large volumes of containing hundreds of cells or large organoids / spheroids while at the same time catching subcellular dynamic structures like filopodia or actin waves. A system to analyze CTL biology in SPIM experiments was developed and established successfully. Having set up 3D imaging methods we aimed to elucidate the function of a protein central to CTL dynamics governed by actin polymerization: profilin. Many cytosolic proteins are involved in cytoskeletal remodeling yet not much is known about the dynamic control in human CTL. Profilin1 (PFN1) an actin binding protein that lies at the border of cytoskeletal dynamics and signaling pathways, was found, by our Chinese collaborators in Shanghai, to be downregulated in CTL from pancreatic cancer patients. Using overexpression systems of PFN1 (and mutations) with fluorescent fusion proteins and siRNA downregulation we could show that PFN1 is a negative regulator of CTL cytotoxicity and that interactions with phospholipids and regulatory proteins are important for proper regulation of migration. Interestingly actin polymerization rates appear almost unaffected by changes of the relative PFN1:G-actin concentration as is the case for overexpression of PFN1, the Y59A (abolished actin binding) mutant and CTL with siRNA downregulation of PFN1. Apart from this we could show that PFN1 in primary human CTL modulates the protrusion pattern during migration and the release of LGs at the IS via actin structure modulation at the IS. This shows that especially the interplay with phospholipid pathways is an important function for PFN1 apart from supplying actin monomers to polymerizing actin filaments. The results of the profilin study were published in 2017 (Schoppmeyer et al. 2017).Zytotoxische T Zellen beschützen uns vor Viren und Tumorzellen und müssen dafür große Distanzen im Körper und Gewebe zurücklegen um infizierte oder transformierte Zellen zu finden und eliminieren. T-Zell Migration ist ein Zusammenspiel von extrazellulären Signalen, physischem Kontakt zu Fasern der extrazellulären Matrix, zytoskeletaler Dynamik und dem intrazellulärer Signalwege. Um das Migrationsverhalten von Lymphozyten zu analysieren habe ich zuerst neue Imaging-Methoden entwickelt in 3D Umgebungen für die Epifluoreszenz- und Lichtblattmikroskopie (Selected Plane Illumination Mikroskopie oder SPIM) mit Kollagen als grundlegender Matrix. Diese Methoden werden in dieser Arbeit als 2D Matrix (Epifluoreszenz) und 3D SPIM (Lichtblattmikroskopie) benannt. Die natürliche und nicht toxische Kollagenmatrix ist biologisch aktiv und polymerisiert unter physiologischen Bedingungen zu schwamm-artigen, porösen, homogene und stabilen Matrizen. Dies macht Kollagen zu dem perfekten Startpunkt zur Remodellierung einer grundlegenden Gewebearchitektur und Bestimmung der Grundlegenden Migrationsparameter von Lymphozyten. Mit Hilfe des Kollagen basierten Systems und einer verflachten Matrix (10 - 15 μm) um eine „out of focus“ Migration der Zellen zu verhindern konnte ich Grundlegende Parameter von primären humanen Lymphozyten von gesunden Spendern mit Hilfe des 2D Matrixsystems bestimmen. Lymphozyten migrieren mit einer Zufallsbewegung mit einer Durchschnittsgeschwindigkeit von etwa 5 μm min-1 und niedriger Persistenz in 0.25 % Kollagen. Bead Stimulation von CTL, welche Effektor und Effektor-Gedächtniszellen in der Population anreichert, erhöht die durchschnittliche Persistenz der Population während die Durchschnittsgeschwindigkeit sich kaum verändert. Durch das Hinzufügen von Komponenten der Extrazellulären Matrix (Fibronektin und Hyaluronsäure) ist es relativ einfach möglich die Matrix und damit das Verhalten der darin migrierenden Zellen zu modulieren. Fibronektin z.B. beeinflusst sowohl die Durchschnittsgeschwindigkeit als auch die Persistenz während Hyaluronsäure nur die Persistenz beeinflusst. Zur Langzeitbeobachtung von Zellen unter physiologischen Bedingungen reicht das 2D Matrix System nicht aus auf Grund seiner Limitationen. Der Transfer des kollagen-basierten Systems zu SPIM erlaubt Langzeitaufnahmen von Zellpopulationen in 3D Volumen unter probenschonenden Bedingungen bei gleichzeitiger subzellulärer Auflösung. Das Aktin-Zytoskelett steht zentral zu dynamischen Prozessen in T Zellen und die Polymerisation von Aktinfilamenten ist die treibende Kraft für die Zellbewegung. Eine Vielzahl an Proteinen sind in der Remodellierun
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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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