1,721,067 research outputs found
Synthesis and activity studies of analogues of the rat selective toxicant norbormide
No full textNorbormide [5-(alpha-hydroxy-alpha-2-pyridylbenzyl)-7-(alpha-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB, 1), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. A series of NRB-related analogues were prepared to investigate the structural features responsible for, and the in vitro biological markers indicative of, in vivo lethality of the parent molecule in rats. Their synthesis and biological evaluation (vasoconstriction, vasodilation, mitochondrial dysfunction, cardiotoxicity and lethality) is described
Design and synthesis of prodrugs of the rat selective toxicant norbormide.
No full textNorbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, one major drawback of NRB as a viable rodenticide relates to an evolutionary aversion developed by the rat leading to sub-lethal dosing due to either its unpleasant 'taste' or rapid onset of effects. A series of NRB prodrugs were prepared in an effort to 'mask' this acute response. Their synthesis and biological evaluation (in vitro vasoconstrictory activity, in vitro hydrolytic and enzymatic stability and lethality/palatability in vivo) is described. Compound 19 displayed the most promising profile with respect to a delay in the onset of symptoms and was subsequently demonstrated to be significantly more palatable to rats
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
Equilibrated structures for the MD simulations
Full text linkSupporting data for Equilibrated structures for the MD simulations. For further detail see 000README.txt and par_all36_prot_lip.prm
For published article see, Bower, RL and Yule, L and Rees, TA and Deganutti, G and Hendrikse, ER and Harris, PWR and Kowalczyk, R and Ridgway, Z and Wong, AG and Swierkula, K and Raleigh, DP and Pioszak, AA and Brimble, MA and Reynolds, CA and Walker, CS and Hay, DL (2018) 'Molecular signature for receptor engagement in the metabolic peptide hormone amylin.' ACS Pharmacology & Translational Science. ISSN 2575-9108 https://pubs.acs.org/doi/10.1021/acsptsci.8b00002 and http://repository.essex.ac.uk/21918
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
Total Synthesis of Lasionectrin and Synthetic Studies Towards Pestaloxazine A
No full textThis thesis describes our efforts towards the synthesis of two natural products which exhibit promising biological activity and is therefore divided in two parts. Part one describes the first enantioselective synthesis and structural confirmation of naphthopyrone lasionectrin (13), which was extracted from the fungus Lasionectra sp. and exhibited antimalarial activity (IC50 = 11 μM). Lasionectrin (13) is a naphthalene derivative which contains a fused pyrone-tetrahydrofuran ring system. Several synthetic strategies were explored to prepare the carbon skeleton of lasionectrin (13). Our initial approach which hinged on formation of the fused bicycle in a single step using chiral hypervalent iodine was ultimately unsuccessful. Our revised synthetic route to lasionectrin (13) involved late-stage installation of the fused pyrone-tetrahydrofuran ring system via tandem dihydroxylation-tosylate displacement beginning from alkene 199, followed by a carboxylation-cyclisation sequence. Key alkene 199 was efficiently assembled with high stereoselectivity from aldehyde 129 and sulfone 119 using a Julia-Kocienski olefination. Part two details our synthetic efforts towards the synthesis of pestaloxazine A (208). Natural product 208 was extracted from a marine-derived fungus belonging to the Pestalotiopis genus, and exhibited antiviral activity against EV71 (IC50 = 16.1 μM). Pestaloxazine A (208) is a racemic alkaloid dimer which contains a unique spiro[1,2-oxazinane-diketopiperazine] moiety. We sought to access the 1,2-oxazinane ring system by the application of oxidative radical cyclisation conditions to a N-hydroxylamine precursor. Our initial synthetic strategy hinged on the preparation of the diketopiperazine ring system prior to installation of the 1,2-oxazine moiety, which was ultimately unsuccessful. Our revised approach involved Mitsunobu reaction of known alcohol 291 and hydroxamate 311 to give hydroxamic acid 309. However, attempts to effect 1,6-hydrogen abstraction with hydroxamic acid 309 to provide the 1,2-oxazine ring system were unsuccessful
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