1,721,062 research outputs found
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
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Identification and Characterization of Transcriptional Regulators as Therapeutic Vulnerabilities in Hematologic Malignancies
No full textTranscription regulation is orchestrated on a chromatin template via the complex interactions between cis-regulatory DNA elements, trans-acting co-regulators, and RNA polymerase (Pol) II. These factors combine to regulate cell-type specific gene expression programs that enable the derivation of diverse cell types from a static genome, or when dysregulated, cause and support oncogenesis. Here, I present a collaborative body of work aimed to identify and delineate the mechanistic role of transcriptional regulators as cancer- specific dependencies.
Our group previously reported dBET1, a proof-of-principle small molecule capable of directing BET family (BRD2, BRD3, and BRD4) proteins for proteasome-dependent degradation. BRD4, which utilizes a pair of tandem bromodomains to bind acetyl-lysine residues in active regions of chromatin, promotes pathogenic transcription in cancer. Using dBET1, our group previously reported BET degradation as having improved anti-cancer activity over BET bromodomain inhibition, but through unclear mechanisms. Here, we use a chemically-optimized degrader molecule to demonstrate that BET degradation results in global shutdown of transcription elongation. While BRD4 has previously been understood to recruit the master regulator of Pol II pause release, P-TEFb, we find persistence of P-TEFb on chromatin following BET degradation. Unexpectedly, recruitment of the transcription elongation factor, SPT5, is globally diminished, repositioning BRD4 as a master regulator of transcription elongation independent of P-TEFb recruitment.
While the function of BRD4 as a principal mediator of oncogenic transcription is well established, the YEATS domain, also an acyl-lysine reader, has remained unexplored in human malignancies. In a genome-scale CRISPR/Cas9 knockout screen of a human acute leukemia cell line, we identified ENL as particularly indispensable for proliferation, an observation extended to diverse acute leukemia cell lines and a xenotransplantation model of disseminated leukemia. Importantly, ENL-dependent leukemic growth was contingent upon an intact YEATS chromatin reader domain. To explain the mechanistic role for ENL in leukemia pathogenesis and dynamic transcription control, we pursued a chemical genetic strategy utilizing targeted protein degradation. Acute ENL loss suppresses transcription initiation and elongation genome- wide, with pronounced effects at genes featuring disproportionate ENL load. These findings reveal a novel dependency in acute leukemia and a first mechanistic rationale for disrupting the YEATS domain in disease.Medical SciencesMedical Science
High-throughput gene expression profiling of memory differentiation in primary human T cells
Full text linkBackground: The differentiation of naive T and B cells into memory lymphocytes is essential for immunity to pathogens. Therapeutic manipulation of this cellular differentiation program could improve vaccine efficacy and the in vitro expansion of memory cells. However, chemical screens to identify compounds that induce memory differentiation have been limited by 1) the lack of reporter-gene or functional assays that can distinguish naive and memory-phenotype T cells at high throughput and 2) a suitable cell-line representative of naive T cells. Results: Here, we describe a method for gene-expression based screening that allows primary naive and memory-phenotype lymphocytes to be discriminated based on complex genes signatures corresponding to these differentiation states. We used ligation-mediated amplification and a fluorescent, bead-based detection system to quantify simultaneously 55 transcripts representing naive and memory-phenotype signatures in purified populations of human T cells. The use of a multi-gene panel allowed better resolution than any constituent single gene. The method was precise, correlated well with Affymetrix microarray data, and could be easily scaled up for high-throughput. Conclusion: This method provides a generic solution for high-throughput differentiation screens in primary human T cells where no single-gene or functional assay is available. This screening platform will allow the identification of small molecules, genes or soluble factors that direct memory differentiation in naive human lymphocytes
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