1,721,121 research outputs found
FAST vs IN-DEPTH CHARACTERIZATION OF NEW CHOLINESTERASES INHIBITORS BY IMMOBILIZED ENZYME REACTORS
No full textThe cholinergic enzymes acetyl- and butyrylcholinesterase (AChE and BuChE, respectively) represent well-known targets for Alzheimer’s Disease (AD) treatment. In particular, the role of AChE on amyloid misfolding and aggregation has been further investigated by transgenic mice overexpressing human acetylcholinesterase and the Swedish amyloid precursor protein mutation [1]. In the search for new cholinesterase inhibitors, high throughput screening techniques are required for hit identification in the early drug discovery process. In this context, immobilized enzyme reactors (IMERs) containing key target enzymes may fulfill pharma industry requirements. Fast and universal screening procedures for natural compounds or new synthetic products would reduce the number of false negative responses and allow a reliable selection of new potential hits. In this work, monolithic immobilized enzyme reactors (IMERs) containing covalently bound AChE or BuChE have been developed, characterized after insertion into HPLC systems, and applied to the screening of known and new inhibitors [2,3]. A specific chromogenic reagent was used to follow product formation and to determine both activity and inhibition. Since screening purpose might differ along drug discovery process and be either focused on fast data output (low information content per compound) or on a deeper investigation (high information content per compound), different operative procedures have been optimized to allow either (i) fast evaluation of different classes of new chemical entities or (ii) a better characterization of the selective active ones, i.e., mechamism of action of reversible and pseudo-irreversible inhibitors [3,4]. Besides, to reduce false negative results, particular attention has been devoted to non specific interaction managment. Even if each IMER has its own requirements for optimal performances, both AChE- and BuChE-IMER showed an increased data output, reliability and stability, which directly translate into cost reduction. Moreover, in
the optimized conditions, fast screening of compounds with different lipophilicity could be performed.
1] Hedberg MM, Svedberg MM, Mustafiz T, Yu W-F, Mousavi M, Guan Z-Z, Unger C, Nordberg A. Neuroscience, 2008, 152, 223-233
[2] Bartolini M, Cavrini V, Andrisano V. J. Chromatogr. A, 2005, 1065: 135-144
[3] Bartolini M, Greig NH, Yu QS., Andrisano V. J. Chromatogr. A, 2009, 1216: 2730-2738
[4] Bartolini M, Cavrini V, Andrisano V. J. Chromatogr. A. 2007, 1144: 102-11
analisi volumetricaper precipitazione, chelometria ed ossidoriduzione
No full textprincipi teorici, metodiche sperimentali ed applicazioni delle analisi volumetriche di precipitazione, chelometriche ed ossido-riduttiv
Il ‘paradigma di Achille’ e la bilancia d’oro di Zeus : a proposito dell’esistenza di un ordine nel mondo
No full text“Stereoselectivity at α-Adrenoreceptor Subtypes: Observations With the enantiomers of WB 4101 Separated Through Their Amides of N-Tosyl-(S)-Proline”.
No full text
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
Bio-guided fractionation of stem bark extracts from phyllanthus muellarianus: Identification of phytocomponents with anti-cholinesterase activity
Full text linkA combination of flash chromatography, solid phase extraction, high-performance liquid chromatography, and in vitro bioassays was used to isolate phytocomponents endowed with anticholinesterase activity in extract from Phyllanthus muellarianus. Phytocomponents responsible for the anti-cholinesterase activity of subfractions PMF1 and PMF4 were identified and re-assayed to confirm their activity. Magnoflorine was identified as an active phytocomponent from PMF1 while nitidine was isolated from PMF4. Magnoflorine was shown to be a selective inhibitor of human butyrylcholinesterase—hBChE (IC50 = 131 ± 9 μM and IC50 = 1120 ± 83 μM, for hBuChE and human acetylcholinesterase—hAChE, respectively), while nitidine showed comparable inhibitory potencies against both enzymes (IC50 = 6.68 ± 0.13 μM and IC50 = 5.31 ± 0.50 μM, for hBChE and hAChE, respectively). When compared with the commercial anti-Alzheimer drug galanthamine, nitidine was as potent as galanthamine against hAChE and one order of magnitude more potent against hBuChE. Furthermore, nitidine also showed significant, although weak, antiaggregating activity towards amyloid-β self-aggregation
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
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