1,721,075 research outputs found
Understanding the molecular mechanisms underpinning the biological activity of antibodies against the inhibitory CD32b receptor
No full textFc gamma receptor (FcγR) IIB (CD32b) is the only inhibitory FcγR in humans and regulates the action of Immunoreceptor Tyrosine-based Activation Motif (ITAM) containing receptors such as the B cell receptor and activatory FcR. The inhibitory actions of CD32b are detrimental in a cancer immunotherapy setting, yet have the potential to regulate aberrant immune responses in autoimmune conditions, making CD32b an attractive target for immunotherapy. A panel of human anti-human CD32b monoclonal antibodies (mAb) were recently developed, capable of blocking IgG immune complex binding to the receptor. Although predicted to bind within a similar region of the receptor, opposing biological responses were observed with these mAb, with some activating the receptor (agonists) and others blocking CD32b phosphorylation and consequent activation (antagonists). This project aimed to identify the molecular mechanisms that determined the agonist or antagonist activity of these anti-CD32b mAb. Microscopy studies revealed that agonist but not antagonist antibodies induced clustering of CD32b, which was necessary for CD32b activation. The ability of the anti-CD32b mAb to cluster CD32b was therefore thought to drive the opposing biological responses observed and was proposed to derive from the subtle differences in epitopes engaged by the agonist and antagonist mAb. The crystal structure of an antagonist complex was not available, therefore small angle X-ray scattering studies were conducted to explore the basis behind the opposing biological responses of the anti-CD32b mAb. In solution, both agonist and antagonist F(ab) were observed to adopt similar conformations. In contrast, when F(ab) were in complex with the extracellular domain of CD32b, antagonist F(ab) appeared to form more elongated complexes with CD32b, showing a greater radius of gyration (Rg) and maximal dimension (Dmax), compared to agonist F(ab):CD32b complexes. Current crystal structures of the agonist 6G08 F(ab):CD32b complex showed poor agreement to the solution data, therefore molecular dynamics simulations were used to determine atomic structures of agonist 6G08 and an antagonist F(ab), 6G11, that agreed with SAXS data for the proteins in solution. The simulations confirmed previous observations from SAXS studies, that these proteins adopted similar conformations in solution. These methods in VI addition to metadynamics were further applied to the crystal structure of the 6G08 F(ab):CD32b complex and a homology model of the antagonist 6G11 F(ab):CD32b complex. The structures identified from these simulations revealed a difference in binding orientation between the agonist and antagonist F(ab), with the 6G11 F(ab) binding in an orientation which resulted in a more linear complex with CD32b in comparison to the 6G08 F(ab). When predicting the interactions of an IgG anti-CD32b mAb at the cell surface, the difference in binding orientation between the 6G08 and 6G11 F(ab) were proposed to result in the CD32b receptors coming in to close proximity when bound to 6G08 IgG, whereas 6G11 IgG was predicted to hold the receptors further apart in the cell membrane. Taken together, a model for determining the biological activity of the anti-CD32b was generated. The model proposes that binding orientation of the F(ab) determines the ability of the anti-CD32b to cluster CD32b in the cell membrane, and that the lower affinity of agonist mAb facilitates clustering of CD32b. In contrast, the extended binding geometry and higher affinity of the antagonist F(ab) results in receptors being held apart in the membrane with less potential for clustering. Further studies will continue to test this model in order to design increasingly effective agonist or antagonist antibodies for the treatment of autoimmunity or cancer, respectively.<br/
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
The sixth sense : synaesthesia and British aestheticism, 1860-1900
No full text“The Sixth Sense: Synaesthesia and British Aestheticism 1860-1900” is an
interdisciplinary examination of the emergence of synaesthesia conceptually and
rhetorically within the ‘art for art’s sake’ movement in mid-to-late Victorian Britain.
Chapter One investigates Swinburne’s focal role as both theorist and literary spokesman
for the nascent British Aesthetic movement. I argue that Swinburne was the first to
practice what Pater meant by ‘aesthetic criticism’ and that synaesthesia played a decisive
role in ‘Aestheticising’ critical discourse.
Chapter Two examines Whistler’s varied motivations for using synaesthetic metaphor,
the way that synaesthesia informed his identity as an aesthete, and the way that critical
reactions to his work played a formative role in linking synaesthesia with Aestheticism in
the popular imagination of Victorian England.
Chapter Three explores Pater’s methods and style as an ‘aesthetic critic.’ Even more than
Swinburne, Pater blurred the distinction between criticism and creation. I use
‘synaesthesia’ to contextualise Pater’s theory of “Anders-streben” and to further
contribute to our understanding of his infamous musical paradigm as a linguistic ideal,
which governed his own approach to critical language.
Chapter Four considers Wilde’s decadent redevelopment of synaesthetic metaphor. I use
‘synaesthesia’ to locate Wilde’s style and theory of style within the context of decadence;
or, to put it another way, to locate decadence within the context of Wilde.
Each chapter examines the highly nuanced claim that art should exist for its own sake and
the ways in which artists in the mid-to-late Victorian period attempted to realise this
desire on theoretical and rhetorical levels
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
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