1,721,023 research outputs found
La religione come fenomeno : Ricerche e studi a partire da Michel Henry
No full textL’incontro tra fenomenologia e religione è da sempre oggetto di vivaci dibattiti. Non è possibile non notare come questo interesse per tematiche inerenti alla sfera del “religioso” attraversi il campo delle ricerche fenomenologiche fin dalla formazione dei primi circoli animati dagli allievi di Husserl.
Pensare, accostandole, fenomenologia e religione non significa però pretendere di subordinare uno dei due termini all’altro. Che cosa vuol dire allora trattare la religione come fenomeno? E che cosa è da intendere per fenomeno? La questione riguarda il “senso” dell’apparire e della connessione che, nel suo darsi, l’apparire offre al pensiero.
Gli studi raccolti in questo volume si confrontano con le sollecitazioni provenienti dalla filosofia di Michel Henry e dal suo progetto di revisione della fenomenologia che, nella sua radicalità, apre lo spazio per ripensare in modo nuovo il legame antico che, nel pensiero dell’origine, vede inestricabilmente intrecciarsi filosofia e religione
The Influence of Different Nitrogen Treatments on the Growth and Yield of Basil (Ocimum Basilicum L.)
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Comparative effects on blood pressure and regional haemodynamics of nicardipine and captopril
No full textBIOCHEMICAL AND STRUCTURAL CHARACTERIZATION OF HUMAN CARBONIC ANHYDRASES
No full textCarbonic anhydrases (CAs. EC 4.2.1.1) are ubiquitous metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and proton. In humans, 15 isozymes have been described with different subcellular localization. Indeed, CA I-III, VII, and XIII are cytosolic, CA IV, IX, XII and XIV are membrane-bound, CA VA and CA VB are mitochondrials, and CA VI is secreted. Human CA isozymes are extensively distributed in several tissues and organs where, as modulators of pH and ion transport, they take part in a variety of physiological and pathological processes. As a result, in the last years many of these enzymes have become important therapeutic targets for pharmaceutical research. However, given the high degree of sequence and structure similarity among the different isoforms, to date most of the CA-directed drugs developed lack of selectivity and consequently present many side-effects. X-Ray crystallography is one of the most useful instruments in the structure-based drug design of selective molecules able to interact with a target enzyme. Indeed, there are several examples in the literature where knowledge of the crystallographic structure of an enzyme allowed the design of molecules able to interact with specific residues, thus regulating enzyme biological activity. This is why in recent years there has been an extensive research effort focusing on the crystal structure resolution of all catalytically active alfa-CA isoforms, with the result that most of the human CA isoforms have been so far structurally characterized. As a part of a general research project based on the structure-based drug design of isoform-selective CA inhibitors (CAIs), my Ph.D thesis has been focused on the study of the biochemical and structural features of two cytosolic CA isoforms, namely hCA VII and hCA I, which among the 15 human isoforms have been poorly investigated. hCA VII was the sole cytosolic isozyme, that at the beginning of this Ph.D thesis was not yet structurally characterized. This enzyme, similarly to hCA II, is a very efficient catalyst for hydration of carbon dioxide, being 10-50 times more active compared to other two cytosolic isoforms, hCA I and hCA XIII. However, in contrast to hCA II which is widely spread in human tissues, CA VII has a more limited distribution, being localized mainly in some brain tissues of humans and rats, in stomach, duodenum, colon, liver and skeletal muscle of mice. In the first part of my Ph.D thesis a complete biochemical characterization of this enzyme was carried out. Interestingly, these studies highlighted the capability of two reactive cysteines to be S-glutathionylated during the purification procedures. Since S-glutathionylation was reported in vivo also for another cytosolic CA isozyme, namely CA III, and was associated to a protective response to oxidative stress, this phenomenon was investigated in details also for CA VII. Such studies showed that Cys183 and Cys217 were involved in adduct formation. These reactive cysteines were mutagenized and the corresponding double mutant (C183S/C217S) was expressed. The native enzyme, its double mutant and the S-glutathionylated adduct were fully characterized for their CO2 hydration, esterase and phosphatase activity. These kinetic studies indicated that the modification of Cys183 and/or Cys217 by glutathione does not have a relevant impact on the active site of the enzyme, causing rather small differences in its specific activity. Moreover, an important observation was that hCA VII was highly effective as esterase and phosphatase, compared to other cytosolic CA isoforms, such as CA I, II, III and XIII. These findings seem to indicate that the observed S-glutathionylation, if present in vivo, is not involved in the regulation of the enzyme catalytic activity but rather, as observed for hCA III, can help hCA VII to function as an oxygen radical scavenger to protect cells from oxidative damage. Further in vivo studies are currently underway to investigate this issue. The X-ray crystallographic structure of a hCA VII mutated form in complex with a classical sulfonamide inhibitor, namely acetazolamide, was also solved. A detailed comparison of the obtained structure with those already reported for other CA isozymes provided novel insights into the catalytic properties of this protein family and offered the basis for a mutagenesis approach aimed at determining the contribution of the active site single residues to the enzyme catalytic efficiency. Moreover, on the basis of the structural differences detected within the active site of the various CA isoforms, further prospects for the design of isozyme-specific CA inhibitors have been obtained. hCA I was one of the first members of the CA family to be identified. Even though the 3D structure of this enzyme was first characterized already in 1975, only few structural studies on complexes formed with different inhibitors have been reported so far. Since these studies are fundamental for the drug design of isoform-selective inhibitors, part of this thesis has been dedicated to the structural characterization of a complex that hCA I forms with topiramate (TPM), which is a molecule of pharmacological interest for the treatment of epilepsy. The analysis of the structure of the complex showed that, upon binding of the inhibitor, the active site of hCA I undergoes a profound reorganization, which has never been observed in any other CA/inhibitor complex and might therefore be useful in designing CA inhibitors. Moreover, the comparison with hCA II/TPM and hCA VA/TPM complex structures, previously investigated, showed that a different H-bond network together with the movement of active site residues to accommodate the inhibitor may account for the difference of inhibition constants of TPM towards different CA isozymes. These data may be helpful in the design of CAIs selective for various isozymes
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
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