1,720,956 research outputs found
A palladium-catalyzed route to huperzine A and its analogs and their anticholinesterase activity
No full textHuperzine A is an alkaloid isolated from Huperzia serrata (Thunb.) Trev., a Chinese club moss the extracts of which have been used in Chinese folklore medicine to treat a variety of maladies including memory disorders. Recently, this molecule has attracted widespread attention because of its possible use in the treatment of Alzheimer's disease (AD). We describe herein a palladium-catalyzed bicycloannulation route to this molecule which makes huperzine A available in 40% overall yield. The application of this methodology to seven other huperzine A analogues together with their biological activity in the inhibition of rat cortex acetylcholinesterase (AChE) is detailed herein. None of these new compounds was more potent than the parent structure as AChE inhibitors
Identification of a More Potent Analogue of the Naturally Occurring Alkaloid Huperzine A. Predictive Molecular Modeling of Its Interaction with AChE
No full textHuperzine A (HA), a potent reversible inhibitor of acetylcholinesterase (AChE), is an important psychotherapeutic agent for improving cognitive function in Alzheimer's patients through the enhancement of central cholinergic tone. This molecule takes on added value in that it has recently been shown to exhibit neuroprotective properties (glutamate toxicity blocking activity) in vitro. Based upon our cumulative SAR information and to some extent the predicted binding site of HA within Torpedo AChE, we chose to investigate the synthesis and biology of certain C-10 substituted analogues. The important finding was made that introduction of an axial methyl group into the C-10 position of huperzine A increased the potency for AChE inhibition 8-fold; the corresponding equatorial isomer was about 1.5-fold less active than huperzine A. The introduction of substituents larger than methyl resulted in a drop in activity. For example, the ethyl analogue was found to be about 100-fold less active than huperzine A, indicating that while it is still capable of binding to Torpedo AChE, some steric interaction with the 'walls' of the active site gorge must result. Through the use of molecular modeling methods involving the docking of these analogues to the reported X-ray crystal structure of Torpedo AChE, it is clearly evident that the C-10 axial methyl group points into a hydrophobic region of the enzyme, while the equatorial methyl group is directed to a less favorable hydrophilic region. Substituents larger than methyl were found to result in a conformational energy penalty. The ready explanation of this structure-activity relationship data provides further evidence in support of our modeling studies aimed at establishing huperzine A's binding site in AChE. This knowledge should facilitate the identification of other structural analogues of huperzine A likely to exhibit an improved therapeutic profile
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
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