176 research outputs found
Web-Based Tools for Polypharmacology Prediction
No full textDrug promiscuity or polypharmacology is the ability of small molecules to interact with multiple protein targets simultaneously. In drug discovery, understanding the polypharmacology of potential drug molecules is crucial to improve their efficacy and safety, and to discover the new therapeutic potentials of existing drugs. Over the past decade, several computational methods have been developed to study the polypharmacology of small molecules, many of which are available as Web services. In this chapter, we review some of these Web tools focusing on ligand based approaches. We highlight in particular our recently developed polypharmacology browser (PPB) and its application for finding the side targets of a new inhibitor of the TRPV6 calcium channel
An edition of Ottorino Respighi's Fantasia Slava, p. 50 with an analysis of his early style
No full textFantasia Slava, a 1903 work by Ottorino Respighi (1879-1936) for piano and orchestra, can be considered the embodiment of his early style. The characteristics of this style will be examined through brief analyses of four works written prior to Fantasia Slava: Violin Sonata in D Minor (1897), P. 15; Piano Sonata in F Minor, P. 16 (1897); Six Pieces for Violin and Piano, P. 31 (1901-2); and Piano Quintet in F Minor (1902). The characteristics developed over the course of these pieces directly affected the construction of Fantasia Slava and shows the young composer developing his compositional language. This document also includes an edition of Fantasia Slava for two pianos-one piano designated for the solo and another a piano reduction of the orchestral part. The sole publication of Fantasia Slava is the orchestral score from Ricordi, copyrighted in 1986. It is from this edition that the author has drawn his two-piano edition. The manuscript for Fantasia Slava, P. 50 was not available for review at the time of this document. Permission to utilize the first edition of the work in such a manner was graciously granted by Lucia Castellina, editor at Casa Ricordi, in a November 14, 2013, email to the author. The orchestral reduction is intended to reflect accurately the sonority and scope of the orchestra score, while remaining playable and true to the inherent properties of the modern piano. Critical notes following the edition reflect discrepancies between the orchestral score and the present edition. They also outline salient points regarding the edition's creation. (Published By University of Alabama Libraries
An edition of Ottorino Respighi's Fantasia Slava, p. 50 with an analysis of his early style
No full textElectronic Thesis or DissertationFantasia Slava, a 1903 work by Ottorino Respighi (1879-1936) for piano and orchestra, can be considered the embodiment of his early style. The characteristics of this style will be examined through brief analyses of four works written prior to Fantasia Slava: Violin Sonata in D Minor (1897), P. 15; Piano Sonata in F Minor, P. 16 (1897); Six Pieces for Violin and Piano, P. 31 (1901-2); and Piano Quintet in F Minor (1902). The characteristics developed over the course of these pieces directly affected the construction of Fantasia Slava and shows the young composer developing his compositional language. This document also includes an edition of Fantasia Slava for two pianos-one piano designated for the solo and another a piano reduction of the orchestral part. The sole publication of Fantasia Slava is the orchestral score from Ricordi, copyrighted in 1986. It is from this edition that the author has drawn his two-piano edition. The manuscript for Fantasia Slava, P. 50 was not available for review at the time of this document. Permission to utilize the first edition of the work in such a manner was graciously granted by Lucia Castellina, editor at Casa Ricordi, in a November 14, 2013, email to the author. The orchestral reduction is intended to reflect accurately the sonority and scope of the orchestra score, while remaining playable and true to the inherent properties of the modern piano. Critical notes following the edition reflect discrepancies between the orchestral score and the present edition. They also outline salient points regarding the edition's creation
In Silico Target Prediction for Small Molecules
No full textISSN:1940-6029ISSN:1064-3745ISSN:1940-602
Conceptual structure of SLAVA/FAME/RUHM in Russian, American and German consciousness
No full text© the author(s). This paper investigates similarities and differences in the conceptualization of the lexemes SLAVA, FAME, and RUHM by culture and by individual perceptions among speakers of Russian, American English, and German respectively. Methods consisted of a free association experiment and lexicographic and phraseological analysis using dictionaries and Internet sources. All three cultures characterized the terms both positively and negatively, however each culture's characterization was unique. Russian text sources align 'slava' with wealth, but also with rumor and gossip; American English sources characterize 'fame' as eternal, but also as something to be avoided, while German sources consider 'ruhm' as a good stimulus, but one which may also be accompanied by envy. The cognitive linguistics approach provides exploration of cognitive consciousness at a cultural level as well as in the core, revealing that despite differences across the speakers' cultures, the speakers themselves show more similarity in their perceptions of the corresponding concepts
Conceptual structure of SLAVA/FAME/RUHM in Russian, American and German consciousness
Get PDF© the author(s). This paper investigates similarities and differences in the conceptualization of the lexemes SLAVA, FAME, and RUHM by culture and by individual perceptions among speakers of Russian, American English, and German respectively. Methods consisted of a free association experiment and lexicographic and phraseological analysis using dictionaries and Internet sources. All three cultures characterized the terms both positively and negatively, however each culture's characterization was unique. Russian text sources align 'slava' with wealth, but also with rumor and gossip; American English sources characterize 'fame' as eternal, but also as something to be avoided, while German sources consider 'ruhm' as a good stimulus, but one which may also be accompanied by envy. The cognitive linguistics approach provides exploration of cognitive consciousness at a cultural level as well as in the core, revealing that despite differences across the speakers' cultures, the speakers themselves show more similarity in their perceptions of the corresponding concepts
Cold war whaling: Bellingshausen and the <i>Slava</i> flotilla
No full textABSTRACTOn 7 December 1945 a captured German whaling factory, Wikinger, was allocated to the Soviet Union under the terms of the Potsdam Agreement between that country, the United States and the United Kingdom. In the first section, this article presents the first detailed account of how Wikinger was seized by the Royal Navy and eventually transferred to Soviet ownership. The second section illustrates the hostile attitudes of western governments towards the Slava whaling flotilla during the cold war, and the degree to which their suspicions were focused on the work of scientists assigned to the flotilla. The next four sections trace the fluctuating perceptions and presentations, during the Tsarist and early Soviet periods, of the Imperial Russian Navy's Antarctic expedition of 1819–1821, the problems in respect of Antarctica which confronted Soviet diplomacy and propaganda in the 1940s, and the new story, about Russians having been the first people to discover Antarctica, which was developed in order to address them. It is then possible, in the seventh section, to explain the political utility of the Slava flotilla in the early 1950s. An eighth section sketches the divergent cultural fortunes of the Bellingshausen expedition and the Slava flotilla after the period under consideration.This article discusses the use of whaling and history in support of Soviet Antarctic policy between the end of World War 2 and the International Geophysical Year (IGY) of 1957–1958. But the Slava whaling flotilla did not just play a part in the historicisation of Soviet Antarctic policy. It was itself a historically constituted object, fraught with meanings on both sides of the cold war. For that reason the opportunity is taken to give a more detailed account of the flotilla's origins than has been available hitherto. The author notes that two contributors to this journal have preceded him in some of these matters (Armstrong 1950, 1971; Gan 2009). He ventures to suggest, however, that the connections between whaling, historiography and public information management in Soviet Antarctic policy have not been fully demonstrated before this.</jats:p
Identifizierung und Charakterisierung neuer tumorrelevanter Gene, die unter Kontrolle des Wnt/β-Catenin-Signalwegs stehen
No full textMittels DNA-Microarray-Analyse wurden die Expressionsmuster von C57MG-Wnt-1- und C57MG-pLNCx-Zellen verglichen. 140 differentiell exprimierte Gene wurden identifiziert. Neun Wnt-1-induzierte Gene wurden näher analysiert. Die Gene , und werden entgegengesetzt durch Wnt-1 und durch LiCl reguliert. Untersuchungen des -Promotors weisen auf die Repression von durch den Wnt-Signalweg hin. Das -Gen unterliegt einer Inhibition durch LiCl und Wnt-3a, während langfristige Wnt-1-Einwirkung zur Induktion des Gens in C57MG-Zellen führt, wie Expressions- und Promotoruntersuchungen ergaben. In den verwendeten Zellen kann seine Expression autokrin verstärken und kolokalisiert mit dem PML-Protein. In Brusttumoren der Maus lokalisiert das Protein in Bereichen mit TUNEL-positiven Zellen. NGAL, das menschliche Homolog von , wurde in Darmzelllinien, Tumor- und Normalgeweben untersucht. Die erhaltenen Daten deuten auf komplexe Regulationsmechanismen der Wnt-Zielgene hin.The expression patterns of C57MG-Wnt-1 und C57MG-pLNCx cells were compared by using the DNA microarray technique. 140 differentially expressed genes were identified. Nine Wnt-1 induced genes were further analysed. For , and an opposite regulation by Wnt-1 and by LiCl in the C57MG cells was detected. Studies with the promoter are indicative of the down regulation of the gene by an active Wnt pathway. The gene is subjected to a negative regulation by LiCl and Wnt-3a, whereas long-term activation of the Wnt pathway results in the induction of , as detected by expression and promoter analysis. In the used cells, enhances its own expression in an autokrine manner. The protein localizes together with PML and is detected in TUNEL-positive regions in mouse breast tumours. NGAL, the human homologue of , was analysed in colon cell lines, normal and tumour tissues. The obtained data suggest complex mechanisms of regulation of the Wnt target genes
Positional scanning synthesis of a Peptoid library yields new inducers of apoptosis that target Karyopherins and Tubulin
Get PDFWe describe the synthesis of a library of 11 638 N-alkylglycine peptoid trimers in a positional scanning format with adjustment of reaction conditions to account for different reactivities of the monomer building blocks. Evaluation of the library by high-content phenotypic screening for modulators of the cytoskeleton and mitosis resulted in the identification of two apoptosis-inducing peptoids, which, despite their structural similarity, target different proteins and cellular mechanisms. Whereas one peptoid binds to karyopherins, which mediate nuclear transport, the other N-alkylglycine trimer binds tubulin at the vinca alkaloid binding site.Fil: Vendrell Navarro, Gloria. Institut Max Planck Fur Molekulare Physiologie; Alemania. Consejo Superior de Investigaciones Cientificas; EspañaFil: Rúa, Federico. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bujons, Jordi. Consejo Superior de Investigaciones Cientificas; EspañaFil: Brockmeyer, Andreas. Institut Max Planck Fur Molekulare Physiologie; AlemaniaFil: Janning, Petra . Institut Max Planck Fur Molekulare Physiologie; AlemaniaFil: Ziegler, Slava. Institut Max Planck Fur Molekulare Physiologie; AlemaniaFil: Messeguer, Angel. Consejo Superior de Investigaciones Cientificas; EspañaFil: Waldmann, Herbert. Institut Max Planck Fur Molekulare Physiologie; Alemania. Technische Universitä t Dortmund; Alemani
- …
