44,272 research outputs found
Silencing disease genes in the laboratory and the clinic
No full textSynthetic nucleic acids are commonly used laboratory tools for modulating gene expression and have the potential to be widely used in the clinic. Progress towards nucleic acid drugs, however, has been slow and many challenges remain to be overcome before their full impact on patient care can be understood. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the two most widely used strategies for silencing gene expression. We first describe these two approaches and contrast their relative strengths and weaknesses for laboratory applications. We then review the choices faced during development of clinical candidates and the current state of clinical trials. Attitudes towards clinical development of nucleic acid silencing strategies have repeatedly swung from optimism to depression during the past 20 years. Our goal is to provide the information needed to design robust studies with oligonucleotides, making use of the strengths of each oligonucleotide technology
Effect of chemical modifications on modulation of gene expression by duplex antigene RNAs that are complementary to non-coding transcripts at gene promoters
No full textAntigene RNAs (agRNAs) are small RNA duplexes that target non-coding transcripts rather than mRNA and specifically suppress or activate gene expression in a sequence-dependent manner. For many applications in vivo, it is likely that agRNAs will require chemical modification. We have synthesized agRNAs that contain different classes of chemical modification and have tested their ability to modulate expression of the human progesterone receptor gene. We find that both silencing and activating agRNAs can retain activity after modification. Both guide and passenger strands can be modified and functional agRNAs can contain 2?F-RNA, 2?OMe-RNA, and locked nucleic acid substitutions, or combinations of multiple modifications. The mechanism of agRNA activity appears to be maintained after chemical modification: both native and modified agRNAs modulate recruitment of RNA polymerase II, have the same effect on promoter-derived antisense transcripts, and must be double-stranded. These data demonstrate that agRNA activity is compatible with a wide range of chemical modifications and may facilitate in vivo applications. <br/
The dialogue between the author and the hero in the “Notes” of G. R. Derzhavin
No full textВ центре внимания автора статьи «Записки» Г. Р. Державина, представляющие по своей сути его автобиографию. Труд этот был создан на закате жизни, он включает все важнейшие события жизни Г. Р. Державина, поэта и государственного деятеля. Рассказ ведется от третьего лица, что придает особую атмосферу повествованию, выстраивается своеобразный диалог между автором и героем, все это и является предметом исследования автора статьи.The focus of the author of the article “Notes” G. R. Derzhavin, representing in essence his autobiography. This work was created at the end of his life; it includes all the most important events in the life of G. R. Derzhavin, poet and statesman. The story is told in a third person, which gives a special atmosphere to the story, a certain dialogue emerges between the author and the hero, all this is the subject of the author's research
Applying the heat to research techniques for species conservation
No full textThe definitive version may be found at www.wiley.comClive R. Mcmahon, Corey J. A. Bradshaw and Graeme C. Hay
Supplemental Material - A Joint Model for Disability, Self-Rated Health, and Mortality Among Medicare Beneficiaries—Differences by Chronic Disease and Race/Ethnicity
No full textSupplemental Material for A Joint Model for Disability, Self-Rated Health, and Mortality Among Medicare Beneficiaries—Differences by Chronic Disease and Race/Ethnicity by Ana R. Quiñones, Gail McAvay, Brent Vander Wyk, Ling Han, Corey Nagel, and Heather G. Allore in Journal of Aging and Health.</p
Gravastars in f(R, G) gravity
No full textThis paper is focused on the study of gravitational vacuum stars or, briefly, gravastars in f(R, G) gravity, where R and G stand for the Ricci scalar and Gauss–Bonnet invariant term, respectively. Due to the involvement of highly non-linear differential equations, solutions are found by using some appropriate numerical techniques. The main structure of gravastars has been discussed according to core, shell, and exterior regions for a well-known f(R, G) gravity cosmological model. Mass–radius evolution is described graphically for the considered gravastar, and it is shown that the mass is directly proportional to the radius.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Introduction: Starring the Author
No full textLiterary celebrity is by now a familiar feat of contemporary literary culture, but it continues to raise complex questions about the history and development of fame, the interplay between the cultural marketplace and the official culture of critics and the canon, and the relation between authorial agency and public appropriation. This introduction addresses these questions by approaching literary celebrity as a merging of two discursive constructions: the celebrity-function and the author-function. By combining insights from celebrity studies, literary history and cultural memory studies, the introduction conceptualizes literary celebrity as a discursive construction with several variables, such as the author’s self-presentation, the circulation of his public identity, changing opinions on literature and writership, and the public afterlife of the author’s image
Spherically symmetric solution of f(R,G) gravity at low energy
No full textThe weak-field and slow-motion limit of f(R,G) gravity is developed up to (v/c)(4) order in a spherically symmetric background. Considering the Taylor expansion of a general function f around vanishing values of R and G, we present general vacuum solutions up to (v/c)(4) order for the gravitational field generated by a ball-like source. The spatial behaviors at (v/c)(2) order are the same for f(R,G) gravity and f(R) gravity, and their corresponding real valued static behaviors are presented and compared with the one in general relativity. The static Yukawa-like behavior is proved to be compatible with the previous result of the most general fourth-order theory. At (v/c)(4) order, the static corrections to the Yukawa-like behavior for f(R,G) gravity, f(R) gravity, and the Starobinsky gravity are presented and compared with the one in general relativity.National Natural Science Foundation of China [11120101004, 11475006]SCI(E)[email protected]; [email protected]
Potential role for telavancin in bacteremic infections due to gram-positive pathogens: Focus on staphylococcus aureus
No full textStaphylococcus aureus bacteremia (SAB) is one of the most common serious bacterial infections and the most frequent invasive infection due to methicillin-resistant S. aureus (MRSA). Treatment is challenging, particularly for MRSA, because of limited treatment options. Telavancin is a bactericidal lipoglycopeptide antibiotic that is active against a range of clinically relevant gram-positive pathogens including MRSA. In experimental animal models of sepsis telavancin was shown to be more effective than vancomycin. In clinically evaluable patients enrolled in a pilot study of uncomplicated SAB, cure rates were 88% for telavancin and 89% for standard therapy. Among patients with infection due to only gram-positive pathogens enrolled in the 2 phase 3 studies of telavancin for treatment of hospital-acquired pneumonia, cure rates for those with bacteremic S. aureus pneumonia were 41% (9/22, telavancin) and 40% (10/25, vancomycin) with identical mortality rates. These data support further evaluation of telavancin in larger, prospective studies of SAB
Real Estate Development: An overview
No full textGreen Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Urban Development Managemen
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