1,721,057 research outputs found
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
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
Abstract 4057: Inhibition of polyploidy and senescence induces intrinsic apoptosis in double hit or double expresser DLBCL
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Introduction: Double Hit (DH) or Double Expresser (DE) DLBCL are aggressive Non-Hodgkin’s Lymphomas (NHLs) with translocation or over-expression of MYC and BCL-2 which are incurable with current therapies. MYC is a critical driver of oncogenic phenotypes and regulates expression of numerous genes including aurora kinases (AKs), which are validated drug targets. AKs are over-expressed in DLBCL and AK inhibition in two Phase-II trials of relapsed and refractory B/T-NHL resulted in 20%-30% overall response rate. Bruton’s tyrosine kinase (BTK) plays a central role in B-cell receptor (BCR) signaling and inhibitors of BTK have shown efficacy in B-NHL clinical trials. Targeting CD20 (rituximab) in DLBCL inhibits BCL-2 and induces apoptosis via caspase-3 activation. We hypothesized that DH/DE-DLBCL are amenable to a novel therapeutic strategy of AK, BTK and CD20 inhibition.
Methods: Four DH/DE DLBCL cell lines were evaluated for viability by MTS; polyploidy, senescence and apoptosis by flow cytometry; DNA damage by TUNEL assay. Phospho-BCL-2, -AK and -BTK analysis by western. Safety and efficacy of drug combinations in a mouse xenograft model. Analysis of patient samples and mouse tumors by IHC.
Results: DH/DE-DLBCL cell lines and patient samples displayed over-expression of MYC, BCL-2, BTK and AK-A proteins. Cell viability assays with alisertib alone showed ~30% cell death, while majority of remaining ~70% cells were polyploid and senescent at day-4 (a mechanism of treatment failure). These polyploid and senescent cells (PASC) showed increased levels of phospho-BTK indicating increased BCR signaling (a rationale for combination therapy). We show that alisertib + ibrutinib + rituximab significantly reduced PASCs leading to intrinsic cell death compared to single/double combinations. Dual inhibition of AK + BTK reduced phospho-ERK-1/2, -Bcl-6 and -MYC with increased DNA breaks indicated by up regulation of phospho-H2A-X, -Chk-2, and pro-apoptotic Noxa and Puma proteins. Triple therapy reduced Bcl-2, Bcl-xL and increased Noxa and Puma compromising the mitochondrial outer membrane potential, release of Cyt-C, activation of caspase-3 and induction apoptosis by PARP cleavage. A DLBCL SCID mouse xenograft model showed ibrutinib alone is inactive while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ~25%. TGI for ibrutinib + rituximab was ~50-60%. However, triple therapy showed a TGI of >90% and was well tolerated. Survival analysis: 67% of mice alive at day-89 with triple therapy versus 20% with ibrutinib + rituximab. Other treatments showed no survival past day-52.
Conclusions: A novel triple therapy consisting of alisertib + ibrutinib + rituximab inhibits PASCs induced by AK inhibition in DH/DE-DLBCL leading to a significant anti-proliferative signal and intrinsic apoptosis. Our work provides a rationale for exploring these combinations in the clinic.
Citation Format: Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine M. Spier, Daruka Mahadevan. Inhibition of polyploidy and senescence induces intrinsic apoptosis in double hit or double expresser DLBCL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4057. doi:10.1158/1538-7445.AM2017-4057</jats:p
Translational advances and novel therapies for pancreatic ductal adenocarcinoma: hope or hype?
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