1,721,027 research outputs found
Locked nucleic acids (LNA): versatile tools for designing oligonucleotide decoys with high stability and affinity
No full textDouble-stranded oligodeoxynucleotides (ODN) containing the consensus binding sequence of a transcription
factor are valuable tools for the manipulation of gene expression at the transcriptional level by means of the decoy
strategy. The approach involves flooding the cells with enough ODN decoy to compete for binding of the transcription
factor with its consensus sequence in target genes. The technique has been proven effective in vitro and in vivo,
suggesting its use in therapy. Therefore, great attention has been recently focused on chemical modifications enhancing
biostability of the oligonucleotides so as to improve their pharmacological properties. Unfortunately, benefits in terms of
nuclease resistance have been often negated by a decrease in the affinity and/or specificity of transcription factor binding.
To circumvent these problems, circular dumbbell and chimeric decoy oligonucleotides, the latter comprising a central
stretch of transcription factor recruiting deoxynucleotides flanked by modified nucleotides, have been introduced.
Nevertheless, these approaches have the limitation of leaving the ODNs still sensitive to endonuclease cleavage. To
address these concerns, we have recently investigated the use of a new class of nucleotide analogs termed locked nucleic
acids (LNA) in the designing of decoy molecules for the transcription factor kB (NF-kB). In this article, we review the
advantages of LNA in the design of ODN decoys pointing to the feasibility of introducing modifications in the
transcription factor binding sequence in order to obtain molecules with increased stability compared to end-capped ODNs,
while remaining efficiently recognized by NF-kB
Adaptive Nonlinear Regulation via Gaussian Processes
No full textThe paper deals with the problem of adaptive output regulation of nonlinear systems. Building on the design technique recently proposed in [1], we present a new approach where the regulator's internal model is adapted online via Gaussian Processes. Adaptation is performed by following an "event-triggered"logic and hybrid tools are used to analyse the resulting closed-loop system. Unlike the approach of [1], where the steady-state control policy is supposed to belong to a specific finite-dimensional model set, here we only require smoothness. The paper also presents numerical simulations showing how the proposed method outperforms previous approaches
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
The global cost of pelvic exenteration: in-hospital perioperative costs
No full textNo abstract availabl
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
Transcription factor decoys containing locked nucleic acids
No full textConvegno: Oligonucleotides & Peptides Technologie
Transgene-derived wild-type and mutant ubiquitin affects both proteolysis and transcription in HeLa cells.
No full textConvegno: SIB 2004, 49° Congresso Nazional
- …
