1,720,954 research outputs found
Functional characterisation of cancer-associated fibroblasts from nasopharyngeal carcinoma / Wong Wee Lin
Nasopharyngeal carcinoma (NPC) remains a major health issue in Southern China and
Southeast Asia where the disease is endemic. Whilst the cure rate for early stage NPC is
high, patients often present with late stage diseases and have a 5-year survival rate of less
than 50%. NPC patients often suffer from severe treatment side effects because of the
location of the tumours that is in proximity to various important organs in the head and
neck region. Therefore, alternative therapeutic approaches are needed to improve the
treatment outcomes and reduce patient morbidity. Targeted therapies are not in routine
use to treat NPC and therapeutic advances will require a more detailed understanding of
the molecular basis of the disease. The tumour microenvironment (TME), which consists
of various non-malignant cell types and extracellular matrix proteins, is known to support
tumour development and progression in a number of cancer types. Cancer-associated
fibroblasts (CAFs) are often the pre-eminent cell type within the TME of solid tumours
and a number of tumour promoting properties of CAFs have been described. The role of
CAFs in the pathogenesis of NPC, however, has received little attention. The present
study was designed to phenotypically characterise a panel of CAFs derived from NPC
tumours (NPC-CAFs) by examining their expression of CAF markers (α-SMA, PDPN,
FAPα, PDGFRα/β and CAV-1), degree of senescence as well as to investigate their
functional roles in NPC pathogenesis. The present study showed that the CAF strains
expressed heterogeneous levels of alpha-smooth muscle actin (α-SMA), and interestingly,
the CAF strains with high levels α-SMA also contained a high proportion of senescent
cells. Notably, NPC-CAFs exclusively expressed podoplanin (PDPN), as PDPN
expression was absent in normal fibroblasts. Next, the ability of the CAFs to promote
NPC cell proliferation and migration, and also inhibit EBV-specific CD8 T cell responses
iv
was investigated. MTT cell proliferation assays showed that conditioned media (CM)
from NPC-CAFs had no effect in NPC cell proliferation. However, in transwell migration
and T cell activation assays, CM from NPC-CAFs significantly enhanced the migration
of NPC cells and inhibited IFN-γ production from antigen-stimulated EBV-specific CD8
T cells. Significantly, NPC-CAFs also inhibited CD8 T cells through cell-cell contact and
this effect was likely to be PD-1/PD-L1 independent, as PD-L1 mRNA expression was
not consistently upregulated in these NPC-CAFs. To begin to investigate which secreted
proteins in the CM might be responsible for the effects on NPC cell migration and T cell
activity, cytokine arrays were used to compare the profiles of cytokines secreted by
normal fibroblasts and NPC-CAFs. The analyses revealed that NPC-CAFs had higher
secretion of RANTES, MCP-3 and VEGF A than NPC-CAFs normal fibroblasts.
Collectively, the present study showed that NPC-CAFs are phenotypically distinct from
normal fibroblasts and may contribute to NPC pathogenesis by promoting a more motile
and possibly metastatic phenotype in NPC cells, as well as by contributing to an
immunosuppressive microenvironment. Therefore, the development of strategies to target
CAFs could provide novel therapeutic opportunities for patients with NPC
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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