7,767 research outputs found

    Vapor condensation on a turbulent liquid interface

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    An experimental investigation which seeks the fundamental relationship between the interfacial condensation rate and the parameters which control it when the liquid side is turbulent is discussed. The scaling laws for free-surface condensation are discussed for this case. It is argued that the condensation of cryogenic liquids can, in principle, be simulated in experiments using steam and water. Data are presented for the condensation rate in terms of the dimensionless scaling parameters which involve the fluid properties and the liquid-side turbulence velocity and length scales

    Repair of Aberrant Splicing in Growth Hormone Receptor by Antisense Oligonucleotides Targeting the Splice Sites of a Pseudoexon

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    Context: The GH receptor (GHR) pseudoexon 6 Psi defect is a frequent cause of GH insensitivity (GHI) resulting from a non-functioning GH receptor (GHR). It results in a broad range of phenotypes and may also be present in patients diagnosed as idiopathic short stature.Objective: Our objective was to correct aberrant GHR splicing and inclusion of 6 Psi using exon-skipping antisense oligonucleotides (ASOs).Design and Setting: Three ASOs binding the 5' (ASO-5), 3' (ASO-3), and branch site (ASO-Br) of 6 Psi were tested in an in vitro splicing assay and a cell transfection system. The wild-type (wt) and mutant (mt) DNA minigenes (wt- and mtL1-GHR6 Psi-L2, respectively) were created by inserting the GHR 6 Psi in a well-characterized splice reporter (Adml-par). For the in vitro splicing assay, the wt- and mtL1-GHR6 Psi-L2 were transcribed into pre-mRNA in the presence of [alpha P-32]GTP and incubated with ASOs in HeLa nuclear extracts. For the cell transfection studies, wt-and mtL1-GHR6 Psi-L2 cloned into pcDNA 3.1 were transfected with ASOs into HEK293 cells. After 48 h, RNA was extracted and radiolabeled RT-PCR products quantified.Results: ASO-3 induced an almost complete pseudoexon skipping in vitro and in HEK293 cells. This effect was dose dependent and maximal at 125-250 nM. ASO-5 produced modest pseudoexon skipping, whereas ASO-Br had no effect. Targeting of two splice elements simultaneously was less effective than targeting one. ASO-Br was tested on the wtL1-GHR6 Psi-L2 and did not act as an enhancer of 6 Psi inclusion.Conclusions: The exon-skipping ASO approach was effective in correcting aberrant GHR splicing and may be a promising therapeutic tool. (J Clin Endocrinol Metab 95: 3542-3546, 2010

    Probing the gateway to superheavy nuclei in cranked relativistic Hartree-Bogoliubov theory

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    The cranked relativistic Hartree+Bogoliubov theory has been applied for a systematic study of the nuclei around 254No, the heaviest nuclei for which detailed spectroscopic data are available. The deformation, rotational response, pairing correlations, quasi-particle and other properties of these nuclei have been studied with different relativistic mean field (RMF) parametrizations. For the first time, the quasi-particle spectra of odd deformed nuclei have been calculated in a fully self-consistent way within the framework of the RMF theory. The energies of the spherical subshells, from which active deformed states of these nuclei emerge, are described with an accuracy better than 0.5 MeV for most of the subshells with the NL1 and NL3 parametrizations. However, for a few subshells the discrepancy reach 0.7-1.0 MeV. The implications of these results for the study of superheavy nuclei are discussed.Comment: 7 pages, 3 figures, Proceedings of the Conference on Frontiers of Nuclear Structure, Berkeley, California, July 29th - August 2nd, 2002, UC Berkeley, Clark Kerr Campus, in pres

    Opto-optical modulation in N-(p-methoxybenzylidene)-p-butylaniline

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    A method of opto-optical modulation in liquid crystals is reported. An Ar+-laser beam is employed to modulate a second He–Ne laser. The highest frequency achieved was 1.5 × 103 pulses per second with input modulating powers smaller than 10 mW. A homeotropic N-(p-methoxybenzylidene)-p-butylaniline liquid-crystal cell was employed as the nonlinear medium

    Quantum Walks on Trees with Disorder: Decay, Diffusion, and Localization

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    Quantum walks have been shown to have impressive transport properties compared to classical random walks. However, imperfections in the quantum walk algorithm can destroy any quantum mechanical speed-up due to Anderson localization. We numerically study the effect of static disorder on a quantum walk on the glued trees graph. For small disorder, we find that the dominant effect is a type of quantum decay, and not quantum localization. For intermediate disorder, there is a crossover to diffusive transport, while a localization transition is observed at large disorder, in agreement with Anderson localization on the Cayley tree.Comment: 12 pages, 13 figure

    Liquid crystal hyperbolic metamaterial for wide-angle negative-positive refraction and reflection

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    We show that nanosphere dispersed liquid crystal (NDLC) metamaterial can be characterized in near IR spectral region as an indefinite medium whose real parts of effective ordinary and extraordinary permittivities are opposite in signs. Based on this fact we design a novel electrooptic effect: external electric field driven switch between normal refraction, negative refraction and reflection of TM incident electromagnetic wave from the boundary vacuum/NDLC. A detailed analysis of its functionality is given based on effective medium theory combined with a study of negative refraction in anisotropic metamaterials, and Finite Elements simulations

    Ultrafast Optical Signal Processing with Bragg Structures

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    The phase, amplitude, speed, and polarization, in addition to many other properties of light, can be modulated by photonic Bragg structures. In conjunction with nonlinearity and quantum effects, a variety of ensuing micro- or nano-photonic applications can be realized. This paper reviews various optical phenomena in several exemplary 1D Bragg gratings. Important examples are resonantly absorbing photonic structures, chirped Bragg grating, and cholesteric liquid crystals; their unique operation capabilities and key issues are considered in detail. These Bragg structures are expected to be used in wide-spread applications involving light field modulations, especially in the rapidly advancing field of ultrafast optical signal processing.Comment: To be published in a special issue of journal Applied Sciences, on the topic of Guided-Wave Optic

    Splicing therapeutics in SMN2 and APOB

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    Splicing therapeutics are defined as the deliberate modification of RNA splicing to achieve therapeutic goals. Various techniques for splicing therapeutics have been described, and most of these involve the use of antisense oligonucleotide-based compounds that target key elements in the pre-mRNA to control splicing in the nucleus. In this review, recent developments in splicing therapeutics for the treatment of two specific diseases are described: correcting the alternative splicing of survival of motor neuron (SMN)2 pre-mRNA to compensate for the defective SMN1 gene in spinal muscular atrophy, and re-engineering the splicing of apolipoprotein B pre-mRNA to lower circulating cholesterol levels

    Minimum target prices for production of direct acting antivirals and associated diagnostics to combat Hepatitis C Virus

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    Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US122perpersonforsofosbuvir+daclatasvir;US122 per person for sofosbuvir+daclatasvir; US152 for sofosbuvir+ribavirin; US192forsofosbuvir+ledipasvir;andUS192 for sofosbuvir+ledipasvir; and US115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US90forgenotypingUS90 for genotyping US34 for two HCV antigen tests and US22fortwofullbloodcount/clinicalchemistrytests.Conclusions:MinimumcostsoftreatmentanddiagnosticstocurehepatitisCvirusinfectionwereestimatedatUS22 for two full blood count/clinical chemistry tests. Conclusions: Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. (Hepatology 2015;61:1174–1182
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