322,905 research outputs found
Geological map of the San Venanzo volcano (Central Italy): explanatory notes.
No full textThe volcanics of the San Venanzo area (Terni) were erupted from three local vents that built up small asymmetric pyroclastic structures associated with lava flows: San Venanzo-maar to the north; Pian di Celle tuff-ring, less than one kilometre south of San Venanzo; and Celli lapilli-cone, about 500 metres east of Pian di Celle. The volcanic morphologies, and the maar-diatreme crater structures in particular, are fairly well preserved. Explosive activity produced about 6X106 m3 of pyroclastic material, mostly lapilli-sized, whereas more than 1x106 m3 of lava was outpoured. The overall sequence shows that the initial crater-forming explosions were followed by strombolian activity. The San Venanzo eruptions caused progressive widening and deepening of the craters, which remained set in the sedimentary substratum. The initial products of San Venanzo volcano consist of breccias containing large accessory-blocks coming from the sedimentary substratum. Late products consist of mainly lapilli-sized juvenile deposits. Pyroclastic surge and minor pyroclastic flow are the main depositional mechanisms. The presence of nucleated, concentric-shelled glassy "lapilli" formed in subvolcanic conditions is typical and is associated with the mobilisation and eruption of diatremic breccia (tuffisite). The juvenile fraction of the pyroclastic rocks contains large amounts of calcite up to 50% in vol., whose composition and texture are suggestive of a magmatic origin. Numerous levels of fine-grained primary calcite, with volcanic-sedimentary structures, are considered as products of the fall of carbonatite ash
Tautomer Enumeration and Stability Prediction for Virtual Screening on Large Chemical Databases
No full textMultiscale modeling shows that dielectric differences make NaV channels faster than KV channels
No full textThe generation of action potentials in excitable cells requires different activation kinetics of voltage-gated Na (NaV) and K (KV) channels. NaV channels activate much faster and allow the initial Na+ influx that generates the depolarizing phase and propagates the signal. Recent experimental results suggest that the molecular basis for this kinetic difference is an amino acid side chain located in the gating pore of the voltage sensor domain, which is a highly conserved isoleucine in KV channels but an equally highly conserved threonine in NaV channels. Mutagenesis suggests that the hydrophobicity of this side chain in Shaker KV channels regulates the energetic barrier that gating charges cross as they move through the gating pore and control the rate of channel opening. We use a multiscale modeling approach to test this hypothesis. We use high-resolution molecular dynamics to study the effect of the mutation on polarization charge within the gating pore. We then incorporate these results in a lower-resolution model of voltage gating to predict the effect of the mutation on the movement of gating charges. The predictions of our hierarchical model are fully consistent with the tested hypothesis, thus suggesting that the faster activation kinetics of NaV channels comes from a stronger dielectric polarization by threonine (NaV channel) produced as the first gating charge enters the gating pore compared with isoleucine (KV channel)
Un caso di sospetta malformazione vertebrale complessa (CVM) in un vitello frisone di 6 mesi
No full textDiffusive author(s), cohesive author: Analysis of S/N (1994)
No full textThis study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Characterization of Primary Cultures of Normal and Neoplastic Canine Melanocytes
No full textAlthough numerous animal models, especially mouse models, have been established for the study of melanoma, they often fail to accurately describe the mechanisms of human disease because of their anatomic, physiological, and immune differences. The dog, as a spontaneous model of melanoma, is nowadays considered one of the most valid alternatives due to the heterogeneity of clinical presentations and of histological and genetic similarities of canine melanoma with the human counterpart. The aim of the study was to optimize a protocol for the isolation and cultivation of healthy and neoplastic canine melanocytes derived from the same animal and obtained from cutaneous and mucosal (oral) sites. We obtained five primary tumor cell cultures (from 2 cutaneous melanoma, 2 mucosal melanoma and 1 lymph node metastasis) and primary normal melanocyte cell cultures (from normal skin and mucosa) from the same dogs. Immunocytochemical characterization with Melan A, PNL2 and S100 antibodies confirmed the melanocytic origin of the cells. This work contributes to expanding the case record of studies on canine melanoma cell cultures as suitable model to study human and canine melanoma. To the authors’ knowledge, this is the first report of isolation of normal skin and mucosal canine melanocytes
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Design, synthesis, characterization, and biological activity of new derivatives of elagolix, a potent GnRH antagonist
No full textBackground: Elagolix, the first orally active gonadotropin-releasing hormone (GnRH or LHRH) antagonist, approved by FDA in 2018 for the treatment of endometriosis [1], is a uracil-based derivative having a stereocenter with the (R)-configuration and a second source of chirality, called atropisomerism. The methyl group at the 6-position of uracil and the fluorine at the ortho position of the 5-aryl group causes a slow rotation around the C-C bond between the two aromatic rings.
Previous studies on two analogues of elagolix [2] evidenced a stereo-preference for receptor interaction toward one of the isolated atropisomers and showed that the elimination of atropisomerism decreased the activity.
Aims: Since the increase in the steric hindrance or the modulation of electronic factors, which can affect the atropisomeric propensity, have not been evaluated yet, the aim of this project is the design, synthesis, characterization, and biological evaluation of new potential uracil-based GnRH antagonists to gain a deeper knowledge about the role of atropisomerism for this class of compounds.
Methods: This project exploits a multidisciplinary approach starting from the synthesis of elagolix, followed by the design (by the aid of molecular modelling techniques) and the synthesis of new derivatives as single thermally stable atropisomers. The compounds will be fully characterized by their physico-chemical properties (NMR, MS, XRD) and biological activity (in vitro binding to the pituitary and peripheral GnRH receptors) after the separation of the two isomers, achieved by traditional methods or by biotransformation.
Results: The synthesis of elagolix was accomplished implementing some modifications with respect to a literature procedure. The NMR and HPLC analyses performed on this molecule confirmed that, in solution, elagolix exists as an interchangeable mixture of atropisomers. The design, through molecular modelling techniques, and the synthesis of some new derivatives will be presented.
Conclusion: This project aims at disclosing new potential orally available GnRH antagonists. The synthesis, separation, characterization, and biological evaluation of the obtained mixtures of atropisomers will provide information to clarify the interaction mechanism of this class of analogues with their target.
References:
1. Lamb, Y. N. Elagolix: First Global Approval. Drugs 2018, 78 (14), 1501-1508.
2. Zhao, L.; Guo, Z. Q.; Chen, Y. S.; Hu, T.; Wu, D. P.; Zhu, Y. F.; Rowbottom, M.; Gross, T. D.; Tucci, F. C.; Struthers, R. S.; Xie, Q.; Chen, C. 5-Aryluracils as potent GnRH antagonists—Characterization of atropisomers. Bioorg. Med. Chem. Lett. 2008, 18 (11), 3344-3349
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