Restoration of Full-Length SMN Promoted by Adenoviral Vectors Expressing RNA Antisense Oligonucleotides Embedded in U7 snRNAs

Background: Spinal Muscular Atrophy (SMA) is an autosomal recessive disease that leads to specific loss of motor neurons. It is caused by deletions or mutations of the survival of motor neuron 1 gene (SMN1). The remaining copy of the gene, SMN2, generates only low levels of the SMN protein due to a mutation in SMN2 exon 7 that leads to exon skipping. Methodology/Principal Findings: To correct SMN2 splicing, we use Adenovirus type 5–derived vectors to express SMN2antisense U7 snRNA oligonucleotides targeting the SMN intron 7/exon 8 junction. Infection of SMA type I–derived patient fibroblasts with these vectors resulted in increased levels of exon 7 inclusion, upregulating the expression of SMN to similar levels as in non–SMA control cells. Conclusions/Significance: These results show that Adenovirus type 5–derived vectors delivering U7 antisense oligonucleotides can efficiently restore full-length SMN protein and suggest that the viral vector-mediated oligonucleotide application may be a suitable therapeutic approach to counteract SMA

Fabrication and performance of selectively oxidized vertical-cavity lasers

Includes bibliographical references.We report the high yield fabrication and reproducible performance of selectively oxidized vertical-cavity surface emitting lasers. We show that linear oxidation rates of AlGaAs without an induction period allows reproducible fabrication of buried oxide current apertures within monolithic distributed Bragg reflectors. The oxide layers do not induce obvious crystalline defects, and continuous wave operation in excess of 650 h has been obtained. The high yield fabrication enables relatively high laser performance over a wide wavelength span. We observe submilliamp threshold currents over a wavelength range of up to 75 nm, and power conversion efficiencies at 1 mW output power of greater than 20% over a 50-nm wavelength range.The work at Sandia National Laboratories was supported in part by the United States DOE under contract No. DE-AC04-94AL85000

Upaya Hukum Dalam Menyelesaikan Perkara Pidana Dengan Negara Lain Menurut Undang-undang Nomor 1 Tahun 2006

Tujuan dilakukan penelitian ini adalah untuk mengetahui bagaimana upaya hukum yang dilakukan negara Republik Indonesia menyelesaikan tindak pidana dengan negara lain dan bagaimana syarat-syarat pemberian bantuan untuk menyelesaikan perkara pidana kepada negara lain. Ruang lingkup penulisan ini adalah pada disiplin ilmu hukum, maka penulisan ini merupakan bagian dari penulisan hukum kepustakaan yakni dengan cara meneliti bahan pustaka atau yang dinamakan penelitian hukum normatif dapat disimpulkan, bahwa: 1. Upaya hukum yang dilakukan untuk negara Republik Indonesia menyelesaikan perkara pidana dengan negara asing, yaitu dengan membuat kesepakatan dalam bentuk perjanjian bilateral maupun multilateral dengan negara asing dan berdasarkan prinsip timbal Balik melalui saluran diplomatik serta pembentukan peraturan Perundang-undangan nasional yang mengatur bantuan timbal Balik dalam masalah pidana. Adanya perjanjian Internasional yaitu dapat memberikan jaminan kepastian hukum yang melandasi hubungan kerjasama Internasional dalam penyelesaian perkara pidana. 2. Syarat-syarat pemberian bantuan untuk menyelesaikan perkara pidana kepada negara lain, yaitu: setiap negara asing dapat mengajukan permintaan Bantuan kepada Pemerintah Republik Indonesia. Negara asing dapat mengajukan permintaan Bantuan secara langsung atau dapat memilih melalui saluran diplomatik

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

Abstract Two new fates of imine intermediates formed on radical cyclizations of ene-sulfonamides have been identified, reduction and hydration/fragmentation. Tin hydride-mediated cyclizations of 2-halo-N-(3-methyl-N-sulfonylindole)anilines provide spiro[indoline-3,3'-indolones] or spiro-3,3'-biindolines (derived from imine reduction), depending on the indole C2 substituent. Cyclizations of 2-haloanilide derivatives of 3-carboxy-N-sulfonyl-2,3-dihydropyrroles also presumably form spiro-imines as primary products. However, the lactam carbonyl group facilitates the ring-opening of these cyclic imines by a new pathway of hydration and retroClaisen-type reaction, providing rearranged 2-(2'-formamidoethyl)oxindoles. 164

InAlGaP vertical cavity surface emitting lasers (VCSELs): Processing and performance

(Al{sub y}Ga{sub 1{minus}y}){sup 1{minus}x}In{sub x}P semiconductor alloys lattice-matched to GaAs are widely used in visible optoelectronic devices. One of the most recent developments in this area is the AlGaInP-based red vertical cavity surface emitting laser (VCSEL). These lasers, which employ AlGaInP active regions and AlGaAs distributed Bragg reflectors (DBRs), have demonstrated continuous-wave (CW) lasing over the 630--690 nm region of the spectrum. Applications for these lasers include plastic fiber data communications, laser printing and bar code scanning. In this paper, the authors present an overview of recent developments in the processing and performance of AlGaInP based VCSELs. This overview will include a review of the general heterostructure designs that have been employed, as well as the performance of lasers fabricated by both ion implantation and selective oxidation

Data-driven Identification of Parametric Governing Equations of Dynamical Systems Using the Signed Cumulative Distribution Transform

This paper presents a novel data-driven approach to identify partial differential equation (PDE) parameters of a dynamical system. Specifically, we adopt a mathematical "transport" model for the solution of the dynamical system at specific spatial locations that allows us to accurately estimate the model parameters, including those associated with structural damage. This is accomplished by means of a newly-developed mathematical transform, the signed cumulative distribution transform (SCDT), which is shown to convert the general nonlinear parameter estimation problem into a simple linear regression. This approach has the additional practical advantage of requiring no a priori knowledge of the source of the excitation (or, alternatively, the initial conditions). By using training data, we devise a coarse regression procedure to recover different PDE parameters from the PDE solution measured at a single location. Numerical experiments show that the proposed regression procedure is capable of detecting and estimating PDE parameters with superior accuracy compared to a number of recently developed machine learning methods. Furthermore, a damage identification experiment conducted on a publicly available dataset provides strong evidence of the proposed method's effectiveness in structural health monitoring (SHM) applications. The Python implementation of the proposed system identification technique is integrated as a part of the software package PyTransKit (https://github.com/rohdelab/PyTransKit)

Hippocampal Contributions to the Large-Scale Episodic Memory Network Predict Vivid Visual Memories

† The first two authors contributed equally to this work. Abstract A common approach in memory research is to isolate the function(s) of individual brain regions, such as the hippocampus, without addressing how those regions interact with the larger network. To investigate the properties of the hippocampus embedded within large-scale networks, we used functional magnetic resonance imaging and graph theory to characterize complex hippocampal interactions during the active retrieval of vivid versus dim visual memories. The study yielded 4 main findings. First, the right hippocampus displayed greater communication efficiency with the network (shorter path length) and became a more convergent structure for information integration (higher centrality measures) for vivid than dim memories. Second, vivid minus dim differences in our graph theory measures of interest were greater in magnitude for the right hippocampus than for any other region in the 90-region network. Moreover, the right hippocampus significantly reorganized its set of direct connections from dim to vivid memory retrieval. Finally, beyond the hippocampus, communication throughout the whole-brain network was more efficient (shorter global path length) for vivid than dim memories. In sum, our findings illustrate how multivariate network analyses can be used to investigate the roles of specific regions within the large-scale network, while also accounting for global network changes

Coupled resonator vertical-cavity laser diode

We report the operation of an electrically injected monolithic coupled resonator vertical cavity laser which consists of an active cavity containing In{sub x}Ga{sub 1{minus}x}As quantum wells optically coupled to a passive GaAs cavity. This device demonstrates novel modulation characteristics arising from dynamic changes in the coupling between the active and passive cavities. A composite mode theory is used to model the output modulation of the coupled resonator vertical cavity laser. It is shown that the laser intensity can be modulated by either forward or reverse biasing the passive cavity. Under forward biasing, the modulation is due to carrier induced changes in the refractive index, while for reverse bias operation the modulation is caused by field dependent cavity enhanced absorption

Oocyte expression with injection of purified T7 RNA polymerase.

International audienceThe Xenopus oocyte is a widely used system for protein expression. Investigators have had the choice between two different techniques: injection into the cytoplasm of in vitro transcribed complementary RNA (cRNA) or injection into the nucleus of complementary DNA (cDNA). We report on a third expression technique that is based on the combined injection of cDNA and purified T7 RNA polymerase directly into the cytoplasm of oocytes