1,720,963 research outputs found
Der Transkritionsfaktor 'basic krueppel-like factor' fördert dieEntwicklung der B Zellen der Marginal-Zone in der Milz
No full textBasic Krüppel-like factor (BKLF) was identified as a proviral integration site in the A-MuLV induced pre-B cell line 18-81. Unlike other pre-B cell lines, 18-81 constitutively undergoes somatic hypermutation (SHM) and is capable of class switch recombination (CSR) upon stimulation. Both processes are mediated by the activation induced cytidine deaminase (AID), an enzyme which is highly expressed in this cell line. It has been proposed that BKLF might be involved in SHM and/or CSR by, for instance, modulating AID activity.
BKLF belongs to the SP/KLF superfamily of transcription factors. Its biological function is poorly understood. To study the role of BKLF in B cell development and function BKLF Tg mice were generated, were BKLF expression is driven by the CD19 promoter. Preliminary analysis showed that BKLF transgenic mice show 3-10 fold increase in the number of marginal zone (MZ) B cells. Also, upon stimulation with LPS and IL-4 in vitro lymph node B cells from BKLF Tg mice showed increased rates of CSR towards IgG1.
In this study using competitive bone marrow of foetal liver reconstitution experiments it was demonstrated that BKLF overexpression promotes MZ B cell development cell autonomously, and does not lead to defective production of follicular B cells. BKLF transgenic mice showed no difference in response to T cell-dependent and independent antigens after primary immunisation as compared to wt mice. IgM response to secondary immunisation with T cell dependent antigen was almost absent in BKLF transgenic mice, whereas secondary IgG1 response was of the same magnitude as in wt animals. BKLF overexpression did not induce SHM in resting B cells. The accumulation of MZ B cells in BKLF Tg mice was not due to alterations in the expression of adhesion molecules, migration, or BCR signalling. Injection of BKLF Tg mice with presenilin inhibitor demonstrated that BKLF overexpression is unable to protect MZ B cell compartment in the absence of Notch signalling. This experiment also demonstrated that in contrast to previous reports, Notch signalling is not only required for the development of MZ B cells, but also for their maintenance. Finally, BKLF overexpression could not substitute for the pro-survival activity of BAFF, but could restore MZ B cell development in the mouse model where BAFF ablation was combined with the overexpression of an anti-apoptotic protein bcl-2. Thus, BKLF might act downstream of BAFF receptor, most probably as one of NF-kappaB target genes.In der pre-B Zelllinie 18-81 liegt die provirale Integration im Lokus des ‘Basic Krüppel-like factors’ (BKLF), welcher zur Familie der SP/KLF-Transkriptionsfaktoren zählt. Im Gegensatz zu anderen pre-B Zelllininien hat 18-81 eine konstitutive Hypermutations-Aktivität (SHM) und kann angeregt werden einen Klassenwechsel der Immunglobuline (CSR) durchzuführen. Für beide Prozesse ist das Enzym 'Aktivierungs-induzierte Cytidin-Deaminase’ (AID) erforderlich, welches 18-81 exprimiert. Es wurde vorgeschlagen, dass BKLF in der Regulierung der SHM und/oder der CSR involviert ist, z.B. indem BKLF direkt oder indirekt die Aktivität der AID reguliert.
Da die biologische Funktion von BKLF während der B Zell Entwicklung und in reifen B Zellen wenig verstanden ist wurden transgene Mäuse erzeugt in denen BKLF mittels des CD19-Promoters in B Zellen über-exprimiert wird. Vorhergehende Untersuchungen zeigten, dass in diesen Tieren die Anzahl der B Zellen in der Marginal-Zone (MZ) der Milz 3-10 fach erhöht ist. Weiterhin zeigten Lymph-Knoten B Zellen der transgenen Tiere eine erhöhte Rate der CSR nach IgG1 wenn sie in vitro mit LPS und IL-4 stimuliert wurden.
Hier wurde untersucht ob naive B Zellen von CD19::BKLF transgenen Tieren eine erhöhte Frequenz von somatischen Hypermutationen aufweisen. Dies war nicht der Fall.
Nach der Immunisierung mit T Zell-abhängigen und -unabhängigen Antigenen konnte in CD19::BKLF transgene Tieren kein Unterschied zu nicht-transgenen Tieren in den Serum Antikörper-Titern festgestellt werden. Der Serum IgM-Titer in CD19::BKLF transgenen Tieren nach sekundärer Immunisierung mit einem T Zell-abhängigen Antigen war jedoch wesentlich geringer als in nicht-transgenen Tieren; dagegen waren die IgG1 Titer nach sekundärer Immunisierung vergleichbar hoch.
Die Akkumulierung von MZ B Zellen in CD19::BKLF transgenen Tieren konnte nicht auf Veränderungen in der Expression von Adhäsionsmolekülen, in der Migration oder in der B Zell Rezeptor Signalleitung zurückgeführt werden.
Schliesslich wurden kompetitive Chimären durch Rekonstitution mit fötalen Leberzellen aus Allotyp-markierten wildtyp und CD19::BKLF transgenen Embryonen erzeugt. In diesen Chimären führt die Über-expression von BKLF dazu, dass Zell-autonom die B Zell Reifung in das MZ B Zell-Kompartment gefördert wird, ohne das jedoch die Reifung der follikulären B Zellen beeinträchtigt wäre
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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