1,721,096 research outputs found
Tumors as Wounds that Never Heal:Signaling Modalities Governing Lung Epithelial Repair and Tumor Heterogeneity
No full text189 pg.The attrition of cells within organs necessitates replenishment from tissue resident progenitor populations. Study of the murine lung has suggested a number of niches present at different levels of the airways along the proximal-distal axis responsible for steady state epithelial turnover as well as response to catastrophic injury. Within the distal most bronchiole airspaces, injury resistant cells termed bronchioalveolar stem cells (BASCs) have been reported to reside at the bronchioalveolar duct junction (BADJ). Since the initial reporting of BASCs, controversy over their true nature has confounded progress towards useful application of insights from their biology towards new therapeutic modalities. We report that additional stratification of the Sca-1+, Pecam-, CD45- lung population with the surface marker CD24 yields to the identification of BASC cells in multiple cell populations. Among them, CD24high cells possess characteristics of stem/progenitor cells. Not only do these cells express molecular markers associated with embryonic pluripotency, but harbor self-renewal capacity and the potential to differentiate into multiple bronchial epithelium cell components when orthotopically transplanted in recipient mice. Transcriptional analysis of this cell population revealed activation of specific signaling pathways and the expression of distinct surface markers that unlike Sca-1 have human ortholog, thereby making them potentially useful in a clinical setting. We confirmed the serotonin receptor isoform 2B (HTR2B) was highly expressed and HTR2B axis components to be activated after naphthalene induced Clara cell ablation. Chemical inhibition of HTR2B manifests as a reduction in mitotic cells after injury and a deficit in re-epitheliazation. Furthermore, we observed that modulation of HTR2B impacts the commitment of cells towards different cell state. Activation of HTR2B results in increased number of cells locked in a mesenchymal cell state. Hence, HTR2B signaling is a novel component of the intricate signaling network regulating the homeostasis of bronchial epithelial progenitor of the distal airway. In principle, deregulation of HTR2B might be involved in the promotion of pathological conditions such as COPD, idiopathic fibrosis and NSCLC.Advisor(s): Sordella, Raffaella ; Lowe, Scott W. Committee Member(s): Van Aelst, Linda ; Seeliger, Markus ; Dannenberg, Andrew J.Stony Brook University Libraries. SBU Graduate School in Department of Genetics. Charles Taber (Dean of Graduate School)
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
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
Spatial, temporal and reversible regulation of endogenous gene in vivo using RNA interference
No full textRNA interference is a powerful tool for controlling gene expression in mammalian systems; as such, it has become an effective alternative to conventional knockout approaches. RNAi has proven to be an efficient method to inhibit tumor suppressor gene function and yield insight into the important players in cancer biology. Still, the promise of regulatable RNAi transgenic mice has yet to be realized because the reproducible generation of these animals remains a significant technical limitation. By combining optimized fluorescence-coupled mir30-based shRNA technology with high efficiency ES cell targeting, I have developed a flexible and scalable pipeline for the rapid and reliable production of doxycycline-regulated shRNA transgenic mice. These RNAi mice contain single copy DOX-regulatable shRNAs downstream of the endogenous Collagen Type 1 locus, allowing for spatial, temporal and reversible gene expression in mice. Using this platform, I generated novel DOX-regulated shRNA transgenic lines targeting the bioluminescence reporter Luciferase and endogenous tumor suppressor genes, including Trp53, INK4a and ARF, each showing strong doxycycline-dependent knockdown of its target protein, without disrupting processing of endogenous miRNAs. To study the role of these TSGs in the maintenance of KrasG12D driven lung adenocarcinomas, I crossed these to produce mice bearing an shRNA, CCSP-rtTA (clara cell specific promoter. reverse tet-transactivator), LSL-KrasG12D and LSL-Luciferase alleles. However, owing to the slow rate and high expense of producing quadruple transgenic mice, I later devised a strategy for"speedy" mouse model production. This approach entailed re-derivation of embryonic stem cells harboring the relevant alleles and subsequent generation of"mosaic" models produced by blastocyst injection. Using these RNAi mouse models, I show that INK4a/ARF or Trp53 downregulation by RNAi cooperates with KrasG12D to accelerate lung tumorigenesis and recapitulate the phenotypes of knockout models. Additionally, I investigate whether INK4a/ARF or Trp53 knockdown is required for tumor maintenance. Together, this work built a platform that greatly accelerates the rate at which one can study genetic interactions and tumor maintenance genes and also identify and validate new drug targets in vivo. This approach can be applied to build many other complex cancer models and thus may have significant implications for guiding future therapies.Advisor(s): Scott W. Lowe. Committee Member(s): Senthil K. Muthuswamy; Greg J. Hannon; Howard C. Crawford; Raffaella Sordella; Cijiang HeStony Brook University Libraries. SBU Graduate School in Department of Genetics. Lawrence Martin (Dean of Graduate School)
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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