1,723,394 research outputs found
Discovery of BGB-8035, a Highly Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase for B‑Cell Malignancies and Autoimmune Diseases
No full textBruton’s
tyrosine kinase (BTK) plays an essential role in
B-cell receptor (BCR)-mediated signaling as well as the downstream
signaling pathway for Fc receptors (FcRs). Targeting BTK for B-cell
malignancies by interfering with BCR signaling has been clinically
validated by some covalent inhibitors, but suboptimal kinase selectivity
may lead to some adverse effects, which also makes the clinical development
of autoimmune disease therapy more challenging. The structure–activity
relationship (SAR) starting from zanubrutinib (BGB-3111) leads to a series of highly selective BTK inhibitors,
in which BGB-8035 is located in the ATP
binding pocket and has similar hinge binding to ATP but exhibits high
selectivity over other kinases (EGFR, Tec, etc.). With an excellent
pharmacokinetic profile as well as demonstrated efficacy studies in
oncology and autoimmune disease models, BGB-8035 has been declared a preclinical candidate. However, BGB-8035 showed an inferior toxicity profile compared to
that of BGB-3111
Eléments orbitaux d'étoiles doubles: ADS 5447 et 8035
No full textNous présentons de nouveaux éléments orbitaux pour les étoiles doubles visuelles ADS 5447 et 8035. Ces éléments ont été obtenus en utilisant les dernières mesures que nous avons effectuées avec le tavelographe PISCO et le télescope Zeiss de 102 cm de Merate (Italie), et celles déjà disponibles dans la littérature
Eléments orbitaux d'étoiles doubles: ADS 5447 et ADS 8035
No full textNous présentons de nouveaux éléments orbitaux pour les étoiles doubles visuelles ADS 5447 et 8035. Ces éléments ont été obtenus en utilisant les dernières mesures que nous avons effectuées avec le tavelographe PISCO et le télescope Zeiss de 102 cm de Merate (Italie), et celles déjà disponibles dans la littérature
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
Discovery of BGB-8035, a Highly Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase for B‑Cell Malignancies and Autoimmune Diseases
No full textBruton’s
tyrosine kinase (BTK) plays an essential role in
B-cell receptor (BCR)-mediated signaling as well as the downstream
signaling pathway for Fc receptors (FcRs). Targeting BTK for B-cell
malignancies by interfering with BCR signaling has been clinically
validated by some covalent inhibitors, but suboptimal kinase selectivity
may lead to some adverse effects, which also makes the clinical development
of autoimmune disease therapy more challenging. The structure–activity
relationship (SAR) starting from zanubrutinib (BGB-3111) leads to a series of highly selective BTK inhibitors,
in which BGB-8035 is located in the ATP
binding pocket and has similar hinge binding to ATP but exhibits high
selectivity over other kinases (EGFR, Tec, etc.). With an excellent
pharmacokinetic profile as well as demonstrated efficacy studies in
oncology and autoimmune disease models, BGB-8035 has been declared a preclinical candidate. However, BGB-8035 showed an inferior toxicity profile compared to
that of BGB-3111
Discovery of BGB-8035, a Highly Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase for B‑Cell Malignancies and Autoimmune Diseases
No full textBruton’s
tyrosine kinase (BTK) plays an essential role in
B-cell receptor (BCR)-mediated signaling as well as the downstream
signaling pathway for Fc receptors (FcRs). Targeting BTK for B-cell
malignancies by interfering with BCR signaling has been clinically
validated by some covalent inhibitors, but suboptimal kinase selectivity
may lead to some adverse effects, which also makes the clinical development
of autoimmune disease therapy more challenging. The structure–activity
relationship (SAR) starting from zanubrutinib (BGB-3111) leads to a series of highly selective BTK inhibitors,
in which BGB-8035 is located in the ATP
binding pocket and has similar hinge binding to ATP but exhibits high
selectivity over other kinases (EGFR, Tec, etc.). With an excellent
pharmacokinetic profile as well as demonstrated efficacy studies in
oncology and autoimmune disease models, BGB-8035 has been declared a preclinical candidate. However, BGB-8035 showed an inferior toxicity profile compared to
that of BGB-3111
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
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