1,720,986 research outputs found
Proceedings of the Workshop on Web 3.0: Merging Semantic Web and Social Web, Turin, Italy, June 29, 2009
No full textSynthesis and Antisense Properties of Fluoro Cyclohexenyl Nucleic Acid (F-CeNA), a Nuclease Stable Mimic of 2′-Fluoro RNA
No full textWe report the design and synthesis of 2′-fluoro
cyclohexenyl
nucleic acid (F-CeNA) pyrimidine phosphoramidites and the synthesis
and biophysical, structural, and biological evaluation of modified
oligonucleotides. The synthesis of the nucleoside phosphoramidites
was accomplished in multigram quantities starting from commercially
available methyl-d-mannose pyranoside. Installation of the
fluorine atom was accomplished using nonafluorobutanesulfonyl fluoride,
and the cyclohexenyl ring system was assembled by means of a palladium-catalyzed
Ferrier rearrangement. Installation of the nucleobase was carried
out under Mitsunobu conditions followed by standard protecting group
manipulations to provide the desired pyrimidine phosphoramidites.
Biophysical evaluation indicated that F-CeNA shows behavior similar
to that of a 2′-modified nucleotide, and duplexes with RNA
showed slightly lower duplex thermostability as compared to that of
the more rigid 3′-fluoro hexitol nucleic acid (FHNA). However,
F-CeNA modified oligonucleotides were significantly more stable against
digestion by snake venom phosphodiesterases (SVPD) as compared to
unmodified DNA, 2′-fluoro RNA (FRNA), 2′-methoxyethyl
RNA (MOE), and FHNA modified oligonucleotides. Examination of crystal
structures of a modified DNA heptamer duplex d(GCG)-T*-d(GCG):d(CGCACGC)
by X-ray crystallography indicated that the cyclohexenyl ring system
exhibits both the 3H2 and 2H3 conformations, similar to the C3′-endo/C2′-endo
conformation equilibrium seen in natural furanose nucleosides. In
the 2H3 conformation, the equatorial fluorine
engages in a relatively close contact with C8 (2.94 Å) of the
3′-adjacent dG nucleotide that may represent a pseudo hydrogen
bond. In contrast, the cyclohexenyl ring of F-CeNA was found to exist
exclusively in the 3H2 (C3′-endo like)
conformation in the crystal structure of the modified A-form DNA decamer
duplex [d(GCGTA)-T*-d(ACGC)]2. In an animal experiment,
a 16-mer F-CeNA gapmer ASO showed similar RNA affinity but significantly
improved activity compared to that of a sequence matched MOE ASO,
thus establishing F-CeNA as a useful modification for antisense applications
Synthesis and antisense properties of fluoro cyclohexenyl nucleic acid (F-CeNA), a nuclease stable mimic of 2'-fluoro RNA
No full textWe report the design and synthesis of 2'-fluoro cyclohexenyl nucleic acid (F-CeNA) pyrimidine phosphoramidites and the synthesis and biophysical, structural, and biological evaluation of modified oligonucleotides. The synthesis of the nucleoside phosphoramidites was accomplished in multigram quantities starting from commercially available methyl-d-mannose pyranoside. Installation of the fluorine atom was accomplished using nonafluorobutanesulfonyl fluoride, and the cyclohexenyl ring system was assembled by means of a palladium-catalyzed Ferrier rearrangement. Installation of the nucleobase was carried out under Mitsunobu conditions followed by standard protecting group manipulations to provide the desired pyrimidine phosphoramidites. Biophysical evaluation indicated that F-CeNA shows behavior similar to that of a 2'-modified nucleotide, and duplexes with RNA showed slightly lower duplex thermostability as compared to that of the more rigid 3'-fluoro hexitol nucleic acid (FHNA). However, F-CeNA modified oligonucleotides were significantly more stable against digestion by snake venom phosphodiesterases (SVPD) as compared to unmodified DNA, 2'-fluoro RNA (FRNA), 2'-methoxyethyl RNA (MOE), and FHNA modified oligonucleotides. Examination of crystal structures of a modified DNA heptamer duplex d(GCG)-T*-d(GCG):d(CGCACGC) by X-ray crystallography indicated that the cyclohexenyl ring system exhibits both the (3)H(2) and (2)H(3) conformations, similar to the C3'-endo/C2'-endo conformation equilibrium seen in natural furanose nucleosides. In the (2)H(3) conformation, the equatorial fluorine engages in a relatively close contact with C8 (2.94 Å) of the 3'-adjacent dG nucleotide that may represent a pseudo hydrogen bond. In contrast, the cyclohexenyl ring of F-CeNA was found to exist exclusively in the (3)H(2) (C3'-endo like) conformation in the crystal structure of the modified A-form DNA decamer duplex [d(GCGTA)-T*-d(ACGC)](2.) In an animal experiment, a 16-mer F-CeNA gapmer ASO showed similar RNA affinity but significantly improved activity compared to that of a sequence matched MOE ASO, thus establishing F-CeNA as a useful modification for antisense applications.sponsorship: NIGMS NIH HHS|R01 GM055237status: Publishe
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
A Multidimensional Semantic Framework for Adaptive Hypermedia Systems.
No full textThis paper introduces a multidimensional semantic framework for adaptive systems. Different planes allow us to represent ontologies of user, her actions, context, device, domain, while the intersection between planes allow us to represent the semantic rules for inferring new user features or adaptation strategies. The adoption of ontology-based framework aims at creating a server for user mod-eling and adaptation strateg
Introduzione all'Informatica (Quarta edizione)
No full textIl libro introduce i "non addetti ai lavori" al mondo dell'informatica e dei calcolatori, presentando in modo semplice ma rigoroso i concetti informatici fondamentali. Dopo una breve introduzione sulle caratteristiche funzionali della macchina hardware, la maggior parte del volume è dedicata al software, a partire dall'organizzazione dei diversi tipi di informazione, fino allo studio del software di base e del sistema operativo. L'ultima parte è dedicata all'analisi di varie classi di programmi applicativi, con particolare attenzione alle reti di calcolatori (internet e non solo) e alle funzionalità che queste forniscono. Scritto appositamente per i corsi universitari di informatica, il libro si presenta come un punto di riferimento irrinunciabile per gli studenti grazie ad una trattazione completa ed esauriente e al ricco apparato didattico
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
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