1,720,984 research outputs found
The Tyrosine Kinases Inhibitors (TKI) Staurosporine/Midostaurin Act as Cation Channel Inhibitors with Antiproliferative Effects in DIPG36 and DIPG50 cells
No full textIon channels and transporters are up-regulated in 33% and down-regulated in 48% of cases in paediatric tumour brain. No data are available on ion channels in Diffuse Intrinsic Pontine Glioma (DIPG) which is a rare, paediatric high-grade glioma of pons. Tyrosine kinases have been proposed as molecular targets. Staurosporine (STS) is a multitarget TKI with ion channel modulatory actions. Investigations are carried out on DIPG patient-derived H3.1K27M (DIPG36) and H3.3K27M (DIPG50) cells using staurosporine (STS) and its structural analogue midostaurin (MIDO). We investigated their antiproliferative effects using crystal violet staining and the 96 multi-well CCK-8 assay. On DIPG36, staurosporine 2.14 μM reduced cell survival by -68.94±0.82% and -100±0.40% after 48h and 72h of incubation time, respectively, while midostaurin 2.14 μM was more potent reducing cell survival by -100±18% at all incubation time. On DIPG50 cells, staurosporine 2.14 μM reduced cell survivals by -47±15.14% after 48h and
-94±12.6% after 72h of incubation time, and midostaurin 2.14 μM reduced it by -63.85±14.56% after 48h and -97±12.9% after 72h of incubation time. These data were confirmed using clonogenic assay on DIPG36 cells, in which midostaurin 2.14 μM reduced the number of colonies from N=345 to N=0 after 72h of incubation
time. We failed to collect data on clonogenic assay on the DIPG50 cells because they were not adherent. On concentration-response relationship investigations, both staurosporine and midostaurin (0.1μM-100μM), reduced cell proliferation in the sub-micromolar concentrations. The IC50 of STS in 96-wells CCK-8 assay after 48h of incubation time were: 5x10-10 M in DIPG50 and 8.9x10-8 in DIPG36 cells. Midostaurin showed an IC50 of 10-7 M and 4.739x10-7M respectively, after 48h and 72h of incubation times. The KATP channel blocker repaglinide(0.1μM-200μM) reduced cell proliferation with an IC50 of 80x10-6M on DIPG36 and 20x10-4 M on DIPG50 cells, respectively, after 48h of incubation time. It also caused a partial reduction of the colonies formation while MIDO fully reduced it. Patch-clamp investigations of the whole-cell inward and outwardcation currents showed that, the currents of DIPG36 cells (N cells=20) were acutely inhibited by -74%±56(+20mV Vm), -50%±43 (+40mV Vm) and -46%±30 (+60mV Vm) by STS 2.14μM vs controls. The STSresponsive currents were fully inhibited by the not selective K+ ion channel blockers TEA-BaCl2 (5 mM) and
were sensitive to the KATP channel blocker glibenclamide (100 M). STS reduced the capsazepine-sensitive current recorded at +80mV Vm in the same cells. No data were collected with MIDO in this cell type because of seal instability. On DIPG50 cells (N cells=3), midostaurin 2.14 M at t=0 failed to inhibit the control
currents at negative potentials while after 20 min of incubation time reduced currents by -22% (-60mV Vm) and -28% (-80mV Vm) vs control. At positive potentials, at t=0, MIDO reduced the control currents by -64% (+60mV Vm) with an increasing inhibitory effect of -97% after 20 min (+60mV Vm). These findings suggest that the unselective TKI STS and MIDO showed antiproliferative effects in either DIPG36 and DIPG50 cells
and their action can be mediated by inhibition of cation channels
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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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