1,720,955 research outputs found
Intratumor Heterogeneity Drives the Evolution of Multiple Populations with Metastatic Initiating Capabilities in a Genetically Engineered Mouse Model of Triple Negative Breast Cancer
No full textPh.D.Heterogeneity within primary tumors allows cancer cells to acquire traits advantageous to their survival and growth, but a better understanding of how this heterogeneity influences metastasis is required. Using a genetically engineered mouse model (GEMM) of triple negative breast cancer (TNBC), we investigated the evolution of tumor heterogeneity during disease progression, and its contribution on metastasis. Here, we show that late malignant tumors (LM) have an enhanced ability to invade and form pulmonary metastases compared to early malignant (EM) tumors. To understand the changes taking place during progression to promote this enhanced metastatic capability, we employed bulk RNA-sequencing (RNA seq) and single cell RNA-sequencing (scRNA-seq). RNA-seq revealed that LM tumors are enriched in programs that contribute to invasion and metastasis such as epithelial-mesenchymal-transition (EMT), hypoxia, and ECM-receptor interactions. Even though the contribution of EMT on metastasis is unclear, the significant upregulation of EMT genes in LM tumors led us to assess experimental lung metastases for two canonical EMT markers, EpCAM and Vimentin. We found that lung metastases formed from LM tumors expressed varying levels of Vimentin, which did not always mirror the EMT phenotype of the primary tumor. scRNA-seq revealed the transcriptional heterogeneity that exists between and within LM and EM tumors, showing subpopulations with unique molecular signatures. During tumor progression, LM tumors experience a loss of mammary epithelial lineage as observed by the downregulation in luminal genes such as Krt8, Wfdc18, Ptn, Kit, Barx2, and Prom1. However, LM tumors did not exhibit a gain in basal features (Trp63, Col17a1, and Krt14). To better understand the contribution of tumor heterogeneity on metastasis, we identified three subpopulations that were unique to LM tumors including EpCAM low, EpCAM high Itga2 low, and EpCAM high Itga2 high tumor cells. While EpCAM low subpopulations exhibited an enhanced ability to invade in vitro, EpCAM high subpopulations displayed a greater ability to form lung metastases. Importantly, we found that multiple subpopulations are comprised of metastasis-initiating cells (MICs), and this metastatic capability was independent of their EMT status. Additionally, our findings suggest that mesenchymal-epithelial-transition (MET) is not required for tumor cells to survive and proliferate after the colonization of a secondary site. Collectively, our findings reveal the existence of MICs in multiple tumor subpopulations, and provides insight to the contribution of heterogeneity and EMT on metastasis
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
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
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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