1,721,009 research outputs found
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Rôle de la P-glycoprotéine, un transporteur ABC, sur la distribution cardiaque et tissulaire de la dompéridone et répercussions possibles sur l'intervalle QT
Full text linkThèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal
Études métaboliques des isoenzymes du cytochrome P450 exprimées dans les ventricules de cœurs humains
Full text linkLes isoenzymes du CYP450 sont grandement impliquées dans le métabolisme oxydatif des médicaments et des variations dans leur activité (interactions médicamenteuses, polymorphismes génétiques) peuvent occasionner des changements importants dans les concentrations plasmatiques et tissulaires des médicaments. Le foie régit de façon prédominante les concentrations plasmatiques des médicaments en raison d’une forte concentration des CYP450s dans cet organe. En moyenne, l’élimination d’un médicament par métabolisme représente environ 75% des mécanismes de clairance par rapport à 20% par voie rénale et 10% par la bile sous forme inchangée. Les CYP450s contribuent à environ 75% du métabolisme des médicaments. Il est ainsi logique de s’attarder au comportement et facteurs influençant l’expression et l’activité des CYP450s. L’abondance et la variété des CYP450s exprimés diffèrent entre le foie et les tissus extra-hépatiques. Le rôle de ces isoenzymes dans le devenir extra-hépatique des composés endogènes et exogènes demeure peu étudié malgré leur implication et association reconnue dans certains échecs thérapeutiques, interactions médicamenteuses ou toxicités tissulaires. Le ventricule de cœur humain exprime (ARNmessager) de façon variable certaines isoenzymes dont le CYP1A1, 2B6, 2C8, 2C9, 2D6, 2E1, 2J2, 3A5 et 4A11. La participation de ces isoenzymes exprimées dans la paroi ventriculaire cardiaque dans le métabolisme des médicaments reste à ce jour inconnue. Établir l’existence d’une participation active de certains CYP450s, étudier leur profil métabolique et leur contribution dans la clairance locale tout en déterminant les facteurs responsables de leur variabilité en terme d’activité et d’expression (ARNm) dans le tissu ventriculaire cardiaque humain représente l’objectif principal des travaux de recherche présentés dans cette thèse. Le premier volet fût le développement de cocktails médicamenteux afin d’optimiser la quantité de résultats à travers l’usage unique d’un tissu avec des substrats sélectifs jumelés à des méthodes analytiques ultra-sensibles et spécifiques (manuscrit 1). Parmi les 9 composés testés, les substrats ébastine et chlorzoxazone, substrats-cibles reconnus des isoenzymes CYP2J2 et CYP2E1 respectivement, ont démontré des activités menant à l’étude approfondie de leur profil métabolique généré par la fraction microsomale de ventricules de cœurs humains explantés (MCH). Ces travaux ont démontré une cinétique préférentielle et de très haute affinité par les MCH envers la voie d’hydroxylation de l’ébastine décrite par un modèle Michaelis-Menten. Jumelé à des essais d’inhibition, un lien fût établi, pour la toute première fois, entre l’hydroxylation de l’ébastine et l’isoenzyme CYP2J2 (manuscrit 2).
L’hydroxylation de l’ébastine par les MCH fût aussi reconnue comme étant hautement variable entre des individus adressés à une transplantation cardiaque présentant des cardiomyopathies potentiellement mortelles n’étant plus maîtrisées par les thérapies ou traitements standards. L’objectif de ce dernier volet était d’étudier des facteurs (extrinsèques et intrinsèques, dont le polymorphisme du CYP2J2*7) connus chez ces patients et leur implication dans la variabilité de l’expression du CYP2J2 (ARNm) et de son activité enzymatique, déduite par l’étude du comportement métabolique du marqueur ébastine suite à une analyse des paramètres de cinétique enzymatique (Km, Vmax, CLint). Il a été démontré que le sexe, le côté gauche du ventricule, la prise d’amiodarone et le diagnostic clinique d’ischémie sont associés à la variabilité d’expression (ARNm) et d’activité (Km, Vmax, CLint) du CYP2J2 et expliquent environ 20% de la variabilité observée entre les individus. Il s’agit des premiers travaux expliquant une portion de la variabilité associée à l’expression (ARNm) et l’activité du CYP2J2 dans le ventricule du cœur humain (manuscrit 3). Finalement, nos résultats suggèrent que la capacité métabolique du CYP2J2 au sein des MCH est réelle et importante et pourrait participer aux fluctuations locales des concentrations de médicaments. L’extrapolation des résultats obtenus in vitro à l’échelle in vivo (organe entier) a permis de mettre en perspective la contribution métabolique du CYP2J2 dans le contexte locale physiologique du tissu ventriculaire cardiaque étudié.
Nos résultats appuient la proposition que la concentration libre plasmatique ne reflète pas nécessairement la concentration tissulaire efficace puisque des mécanismes locaux de métabolisme enzymatique (CYP2J2) peuvent grandement faire varier la concentration libre au site d’action intracellulaire. Les résultats obtenus répondent à un besoin en recherche de comprendre le comportement et l’ampleur de la participation de différentes isoenzymes du CYP450 connues s’exprimant dans le cœur humain envers le métabolisme de médicaments s’y distribuant et ultimement prédire leurs concentrations intracellulaires.CYP450 isoenzymes are greatly involved in oxidative drug metabolism and changes in their activity (drug interactions, genetic polymorphisms) can cause significant changes in plasma and tissue concentrations of the drugs. The liver predominantly governs plasma concentrations of drugs because of a high concentration of CYP450s. On average, the elimination of a drug through metabolism accounts for about 75% of clearance mechanisms compared to 20% via renal excretion and 10% via the bile excretion. The CYP450s contribute to about 75% of drug metabolism. It is thus logical to study factors influencing the expression and activity of CYP450s. Abundance and variety of expressed CYP450s differ between the liver and extrahepatic tissues. The role of these enzymes endogenous and drugs concentrations in the extrahepatic tissues is poorly studied despite their involvement and association recognized in some treatment failures, drug interactions or tissue toxicity. The ventricles of the human heart express (messenger RNA) variably some isoenzymes including CYP1A1, 2B6, 2C8, 2C9, 2D6, 2E1, 2J2, 3A5 and 4A11. The participation of these isoenzymes expressed in the cardiac ventricular wall in drug metabolism remains unknown to this day. Establishing the existence of an active participation of some CYP450s, their metabolic profile and contribution to the local clearance and determining factors responsible for variability in activity and expression (mRNA) in the cardiac ventricular tissue human is the main objective of the research presented in this thesis. The first module was the development of drug cocktails to maximize the amount of results through the use of low amount of heart tissue with selective substrates matched with highly sensitive and specific analytical methods (manuscript 1). Of the nine compounds tested 2 substrates, ebastine and chlorzoxazone, probe of CYP2E1 and CYP2J2 respectively, have demonstrated activities leading to a thorough study of their metabolic profile generated by the microsomal fraction of the ventricles of explanted human hearts (MCH). This work demonstrated preferential kinetics, described by a Michaelis-Menten model, and very high affinity towards the MCH hydroxylation pathway for ebastine. Combined with inhibition assays, a link was established, for the first time, between the hydroxylation of ebastine and the isoenzyme CYP2J2 (manuscript 2).
Hydroxylation of ebastine by MCH was also recognized as being highly variable between individuals that went through a heart transplant with life-threatening cardiomyopathies that are no longer controlled by standard therapies or treatments. The aim of this last part was to study factors (extrinsic and intrinsic, such as polymorphism of CYP2J2 * 7) known in these patients and their involvement in the variability of expression (mRNA) and enzymatic activity of CYP2J2 studied through the analysis of the enzyme kinetic profile of ebastine (Km, Vmax, CLint). It has been shown that gender, the left ventricle, use of amiodarone and clinical diagnosis of ischemia were associated with the variability of expression (mRNA) and activity (Km, Vmax, CLint) of CYP2J2 and those factors account for about 20% of the observed variability between individuals. This is the first work to explain a portion of the variability associated with the expression (mRNA) and activity of CYP2J2 in the ventricle of the human heart (manuscript 3). Overall, our results suggested that the metabolic capacity of CYP2J2 by MCH is real and important and could participate in local fluctuations of drug levels. The extrapolation of in vitro results to in vivo scale (whole body) helped to put into perspective the contribution of CYP2J2 in the local physiological context of the cardiac ventricular tissue studied.
Our results support the proposal that the free plasma concentration does not necessarily reflect the effective tissue concentration as local mechanisms, in this case enzymatic metabolism by CYP2J2, could greatly provoke variation in free intracellular concentration at the site of action. The results obtained meet a need in research to understand the behavior and extent of participation of various CYP450 isoenzymes known to be expressed in the human heart on the local metabolism of drugs that are distributed locally and ultimately developing tools to predict the intracellular drug concentrations in the physiological context
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