1,721,033 research outputs found

    Modulation of the Mitochondrial Cyclosporin A-Sensitive Permeability Transition Pore. II. The Minimal Requirements for Pore Induction Underscore a Key Role for Transmembrane Electrical Potential, Matrix pH and Matrix Ca2+

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    This paper reports an investigation on the minimal requirements for induction of the mitochondrial cyclosporin A-sensitive permeability transition pore (MTP). Energized rat liver mitochondria incubated in sucrose medium take up a Ca2+ pulse but do not show activation of the MTP upon addition of fully uncoupling concentrations of carbonyl cyanide-p-trifluoromethoxy-phenyl hydrazone (FCCP). Yet, addition of ruthenium red immediately prior to FCCP or inclusion of acetate or low concentrations of phosphate in the incubation medium restore the ability of FCCP to trigger MTP opening. Since ruthenium red, phosphate, or acetate do not induce the MTP per se, they must act upon some additional factor(s) that counteract the increase of pore "open" probability induced by membrane depolarization (Bernardi, P. (1992) J. Biol. Chem. 267, 8834-8839). We show that two key factors determining the overall probability of pore opening are matrix pH and matrix [Ca2+] when the membrane is depolarized. Indeed, in the absence of ruthenium red, phosphate, or acetate the addition of FCCP is followed by fast Ca2+ efflux on the uniporter mirrored by intense matrix acidification following compensatory H+ influx via FCCP. Ruthenium red prevents both Ca2+ efflux and matrix acidification, acetate mainly prevents matrix acidification, and phosphate both slows down Ca2+ efflux and prevents matrix acidification. Taken together, our data indicate that membrane depolarization is both necessary and sufficient to trigger MTP opening when matrix acidification and rapid Ca2+ efflux are prevented. Thus, the wide variety of MTP "inducing agents" may largely reflect the wide variety of the possible combinatorial effects on the minimal requirements for MTP operation

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    Plaque vulnerability and related coronary event prediction by intravascular ultrasound with virtual histology: "it's a long way to tipperary"?

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    Identification of so-called "vulnerable plaque" or "high-risk" plaques have spawned manifold attempts to develop diagnostic tools capable to afford this task. This task is particularly challenging but the reward is high: local intervention on identified "vulnerable plaque" could preclude plaque thrombosis and possibly prevent acute coronary syndromes. Various imaging techniques are currently under investigation by extensive clinical testing to identify which could become the most sensible and specific modality for vulnerable plaque detection. Noninvasive techniques are fascinating for their easily applicability to a broad population but nowadays are not sufficiently powered for this task. The emerging technologies with the greatest resolution are indeed catheter-based and many intravascular modalities have been developed for identification of "vulnerable plaque". Among these, IVUS-Virtual Histology (TM) (IVUS-VH) is the most promising technique in the field. IVUS-VH offers an in vivo opportunity to assess plaque morphology and histology. IVUS-VH uses underlying frequency information along with echoes intensity, while grey-scale IVUS data are obtained from echoes of different intensity or amplitude. The major advantage of IVUS-VH is that it is based on a device that is practical for use in the clinical setting and that it generates a real-time assessment of plaque morphology. Unfortunately, numerous challenging issues still need to be overcome until the numerous "vulnerable plaques" could be identified and successfully treated. Future efforts may identify plaques that are on a trajectory of evolution toward a vulnerable state, and help us target interventions to those plaques most likely to develop plaque disruption and related complications. (C) 2007 Wiley-Liss, Inc

    Physiological Effectors Modify Voltage Sensing by the Cyclosporin A-Sensitive Permeability Transition Pore of Mitochondria

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    This paper reports an investigation on the modulation of the mitochondrial permeability transition pore (MTP) by the membrane potential. Energized rat liver mitochondria loaded with a small Ca2+ pulse in sucrose medium supplemented with phosphate favor a high MTP "closed" probability because of the high membrane potential and therefore maintain a low permeability to sucrose. Upon depolarization by the addition of fully uncoupling concentrations of carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) mitochondria favor a high MTP "open" probability and rapidly undergo a process of osmotic swelling following sucrose diffusion toward the matrix. A titration with FCCP reveals that discrete subpopulations of mitochondria with different gating potentials for MTP opening may exist, since increasing concentrations of FCCP increase the fraction of mitochondria undergoing osmotic swelling. We show that physiological effectors (Ca2+, Mg2+, ADP, palmitate) modify pore opening in a mitochondrial population by shifting the fraction of mitochondria with a functionally open pore at any given membrane potential. Many inducers and inhibitors may therefore affect the pore directly through an effect on the MTP voltage sensing rather than indirectly through an effect on the membrane potential. Thus, many effectors may induce pore opening by shifting the MTP gating potential to higher levels, whereas many inhibitors may induce pore closure by shifting the MTP gating potential to lower levels

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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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