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Reversion of anergy signatures in clonal CD21low B cells of mixed cryoglobulinemia patients after clearance of HCV viremia with direct-acting antivirals
Full text linkIntroduction
Type II Mixed cryoglobulinemia (MC) is an autoimmune and benign lymphoproliferative disorder caused by
Hepatitis C virus (HCV) and characterized by the expansion of monoclonal CD27+ IgM+ B cells producing a
rheumatoid factor often encoded by the VH1-69 and VK3-20 genes. These cells display peculiar phenotypic and
functional features: in particular, they commonly express low levels of CD21 (CD21low B cells), an array of
inhibitory and apoptosis-related genes and a distinctive pattern of homing receptors, fail to proliferate in
response to the stimulation of BCR or of TLR9 and, similarly to murine B cells made anergic by continual
antigenic stimulation, overexpress pERK and are prone to apoptosis.
Usually MC regresses after eradication of HCV with interferon (IFN), whose immunomodulatory activity might
contribute to this effect; the newly available direct-acting antivirals (DAAs) rapidly suppress HCV viremia in
HCV+MC patients and lack the immunomodulatory properties of IFN.
Aim
To investigate phenotypic and functional changes in clonal B cells of MC patients with sustained virologic
response to DAAs, untangling the effects of BCR disengagement in a human model of virus-driven anergy and
exhaustion.
Results
In patients treated with DAA, B cell phenotype, constitutive and BCR-induced ERK signaling, spontaneous
apoptosis and cell proliferation were analyzed before and after HCV eradication, using healthy donors as
control. Immunophenotyping studies were performed with combinations of fluorochrome-labeled monoclonal
antibodies, using the VH1-69-specific G6 mAb (which recognize an epitope of the VH1-69-encoded protein) to
identify VH1-69+ B cells; spontaneous apoptosis was assessed by staining cells with annexin V and 7-
aminoactinomycin D; the intracellular pERK content was measured by the BD PhosFlow system and
represented as pERK-specific Mean Fluorescence Intensity (MFI); finally, cell proliferation was evaluated at day
5 of in vitro culture by the carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay. All these
experiments have been done by flow cytometry. Phenotypic and functional analyses in untreated patients
were in agreement with previous data showing an anergic status and an exhausted behavior of VH1-69+ CD21low
B cells. After treatment with DAA, when all patients were negative for HCV RNA, it was observed a slow
reduction of VH1-69+ CD21low B cells in peripheral blood; moreover, these cells showed a significantly reduced
constitutive ERK phosphorylation and a significative decrease in spontaneous apoptosis after eradication of the
virus. To investigate whether reduced lifespan was related to ERK signaling, MC B cells were treated with the
MEK/ERK inhibitor U0126; no effect on spontaneous in vitro apoptosis was observed, suggesting that ERK
signaling is not directly involved in the pro-apoptotic pathway of these cells. Despite phenotypic changes,
clonal B cells failed to restore their capacity to proliferate in response to TLR9 stimulation.
Conclusions
Clonal B cells of HCV+MC display signatures of anergy induced by continual BCR occupancy and of exhaustion
driven by chronic viral infection. Anergy features (pERK overexpression and accelerated apoptosis) rapidly
revert after disengagement from HCV; phenotypic and functional features of exhaustion persist for several
months. The rapid clearance of HCV viremia with DAAs offers a unique model for untangling the interplay of
virus-driven anergy and exhaustion in human B cells
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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