1,720,978 research outputs found
Supplementary_Data - The Binding of BF-227-Like Benzoxazoles to Human α-Synuclein and Amyloid β Peptide Fibrils
No full textSupplementary_Data for The Binding of BF-227-Like Benzoxazoles to Human α-Synuclein and Amyloid β Peptide Fibrils by Lee Josephson, Nancy Stratman, YuTing Liu, Fang Qian, Steven H. Liang, Neil Vasdev, and Shil Patel in Molecular Imaging</p
Synthesis and Preclinical Positron Emission Tomography Imaging of the p38 MAPK Inhibitor [<sup>11</sup>C]Talmapimod: Effects of Drug Efflux and Sex Differences
No full textStress-activated kinases are targets
of interest in neurodegenerative
disease due to their involvement in inflammatory signaling and synaptic
dysfunction. The p38α kinase has shown clinical and preclinical
promise as a druggable target in several neurodegenerative conditions.
We report the radiosynthesis and evaluation of the first positron
emission tomography (PET) radiotracer for imaging MAPK p38α/β
through radiolabeling of the inhibitor talmapimod (SCIO-469) with
carbon-11. [11C]Talmapimod was reliably synthesized by
carbon-11 methylation with non-decay corrected radiochemical yields
of 3.1 ± 0.7%, molar activities of 38.9 ± 13 GBq/μmol,
and >95% radiochemical purity (n = 20). Preclinical
PET imaging in rodents revealed a low baseline brain uptake and retention
with standardized uptake values (SUV) of ∼0.2 over 90 min;
however, pretreatment with the P-glycoprotein (P-gp) drug efflux transporter
inhibitor elacridar enabled [11C]talmapimod to pass the
blood–brain barrier (>1.0 SUV) with distinct sex differences
in washout kinetics. Blocking studies with a structurally dissimilar
p38α/β inhibitor, neflamapimod (VX-745), and displacement
imaging studies with talmapimod were attempted in elacridar-pretreated
rodents, but neither compound displaced radiotracer uptake in the
brain of either sex. Ex vivo radiometabolite analysis
revealed substantial differences in the composition of radioactive
species present in blood plasma but not in brain homogenates at 40
min post radiotracer injection. Digital autoradiography in fresh-frozen
rodent brain tissue confirmed that the radiotracer signal was largely
non-displaceable in vitro, where self-blocking and
blocking with neflamapimod marginally decreased the total signal by
12.9 ± 8.8% and 2.66 ± 2.1% in C57bl/6 healthy controls
and 29.3 ± 2.7% and 26.7 ± 12% in Tg2576 rodent brains,
respectively. An MDCK-MDR1 assay suggests that talmapimod is likely
to suffer from drug efflux in humans as well as rodents. Future efforts
should focus on radiolabeling p38 inhibitors from other structural
classes to avoid P-gp efflux and non-displaceable binding
Copper(I)-Mediated <sup>11</sup>C‑Carboxylation of (Hetero)arylstannanes
No full textA novel
copper-mediated carboxylation strategy of aryl- and heteroaryl-stannanes
is described. The method serves as a mild (i.e., 1 atm) carboxylation
method using stable carbon dioxide and is transferable as a radiosynthetic
approach for carbon-11-labeled aromatic and heteroaromatic carboxylic
acids using sub-stoichiometric quantities of [11C]CO2. The methodology was applied to the radiosynthesis of the
retinoid X receptor agonist, [11C]bexarotene, with a decay-corrected
radiochemical yield of 32 ± 5% and molar activity of 38 ±
23 GBq/μmol (n = 3)
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
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