1,721,208 research outputs found
ON-LINE CHARACTERIZATION OF CHOLINESTERASE INHIBITORS BY IMMOBILIZED ENZYME REACTORS
No full textIn the search for new therapeutics for Alzheimer’s Disease (AD), the investigation of the mechanism of action of new cholinesterase inhibitors represents a key aspect for new lead selection and subsequent optimization and development. However, the in vitro characterization of drug candidates on isolated target enzymes often requires a long operating time and a large amount of disposable expensive material. The recent development and aplication of stable immobilized enzyme reactors (IMERs) can ameliorate these concerns, and such in-solution methods should be potentially utilized in automated procedures to obtain efficient and effective higher throughput screening. In this context, the focus of this work was the development and characterization of a new IMER containing immobilized human recombinant butyrylcholinesterase (BChE) for the on-line kinetic characterization of specific, pseudo-irreversible and brain-targeted BChE inhibitors as potential drug candidates for AD. The selected phenserine and cymserine analogues were synthesized, characterized by classical ex vivo binding assays [1], and assessed by BChE-IMER.
For a pseudo-irreversible inhibitor, the kinetics constants describe the mode and duration of enzyme inhibition that will, in turn, influence the duration of the inhibitors’s in vivo pharmacological actions. The kinetic constants were determined for selected phenserine and cymserine analogues using a purposely-designed on-line procedure. Specifically, agents were inserted on to the BChE-IMER that fed directly into a HPLC system connected to a UV-Vis detector, BChE-IMER activity was determined on the basis of the Ellman reaction [2]. The carbamoylation and decarbamoylation phases at different inhibitor concentrations were then monitored continuously over time. Results allowed elucidation of the inhibition duration, mode of action and structure-activity relationships of the inhibitors of interest, which were compared to available values deriving from classical assessment.
(1) N.H. Greig, T. Utsuki, D.K. Ingram, Y. Wang, G. Pepeu, C. Scali, Q.S. Yu, I. Mamczarz, H.W. Holloway, T. Giordano, D. Chen, K. Furukawa, K. Sambamurti, A. Brossi, D.K. Lahiri: Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent. Proc Natl Acad Sci USA 2005, 102: 17213-18.
(2) G.L. Ellman, K.D. Courtney, V. Jr. Andres, R.M. Featherstone. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961, 7: 88-95
3,6'-Dithiothalidomide treatment attenuates neuroinflammation, memory deficits and hippocampal neurogenesis in response to Aβ1-42 intracerebroventricular injection in mice
No full textsj-docx-1-cll-10.1177_09636897241237049 – Supplemental material for Pomalidomide Improves Motor Behavioral Deficits and Protects Cerebral Cortex and Striatum Against Neurodegeneration Through a Reduction of Oxidative/Nitrosative Damages and Neuroinflammation After Traumatic Brain Injury
No full textSupplemental material, sj-docx-1-cll-10.1177_09636897241237049 for Pomalidomide Improves Motor Behavioral Deficits and Protects Cerebral Cortex and Striatum Against Neurodegeneration Through a Reduction of Oxidative/Nitrosative Damages and Neuroinflammation After Traumatic Brain Injury by Ya-Ni Huang, Nigel H. Greig, Pen-Sen Huang, Yung-Hsiao Chiang, Alan Hoffer, Chih-Hao Yang, David Tweedie, Ying Chen, Ju-Chi Ou and Jia-Yi Wang in Cell Transplantation</p
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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