8,974 research outputs found

    Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus.

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    Usher 1 patients are born profoundly deaf and then develop retinal degeneration. Thus they are readily identified before the onset of retinal degeneration, making gene therapy a viable strategy to prevent their blindness. Here, we have investigated the use of adeno-associated viruses (AAVs) for the delivery of the Usher 1B gene, MYO7A, to retinal cells in cell culture and in Myo7a-null mice. MYO7A cDNA, under control of a smCBA promoter, was packaged in single AAV2 and AAV5 vectors and as two overlapping halves in dual AAV2 vectors. The 7.9-kb smCBA-MYO7A exceeds the capacity of an AAV vector; packaging of such oversized constructs into single AAV vectors may involve fragmentation of the gene. Nevertheless, the AAV2 and AAV5 single vector preparations successfully transduced photoreceptor and retinal pigment epithelium cells, resulting in functional, full-length MYO7A protein and correction of mutant phenotypes, suggesting successful homologous recombination of gene fragments. With discrete, conventional-sized dual AAV2 vectors, full-length MYO7A was detected, but the level of protein expression was variable, and only a minority of cells showed phenotype correction. Our results show that MYO7A therapy with AAV2 or AAV5 single vectors is efficacious; however, the dual AAV2 approach proved to be less effective

    Inoculation of peritoneal dialysate fluid into blood culture bottles improves culture rates

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    The aim of he study was to determine if direct inoculation of peritoneal fluid into Bactec blood culture bottles would improve the positive bacteriological yield compared with conventional techniques in continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis. All patients presenting with suspected peritonitis had peritoneal fluid injected directly into aerobic and anaerobic Bactec blood culture bottles as well as into sterile culture tubes. Thirty-seven paired samples were analyzed.The aim of he study was to determine if direct inoculation of peritoneal fluid into Bactec blood culture bottles would improve the positive bacteriological yield compared with conventional techniques in continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis. All patients presenting with suspected peritonitis had peritoneal fluid injected directly into aerobic and anaerobic Bactec blood culture bottles as well as into sterile culture tubes. Thirty-seven paired samples were analyzed

    MetaboLab - advanced NMR data processing and analysis for metabolomics

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    Background\ud Despite wide-spread use of Nuclear Magnetic Resonance (NMR) in metabolomics for the analysis of biological samples there is a lack of graphically driven, publicly available software to process large one and two-dimensional NMR data sets for statistical analysis.\ud \ud Results\ud Here we present MetaboLab, a MATLAB based software package that facilitates NMR data processing by providing automated algorithms for processing series of spectra in a reproducible fashion. A graphical user interface provides easy access to all steps of data processing via a script builder to generate MATLAB scripts, providing an option to alter code manually. The analysis of two-dimensional spectra (1H,13C-HSQC spectra) is facilitated by the use of a spectral library derived from publicly available databases which can be extended readily. The software allows to display specific metabolites in small regions of interest where signals can be picked. To facilitate the analysis of series of two-dimensional spectra, different spectra can be overlaid and assignments can be transferred between spectra. The software includes mechanisms to account for overlapping signals by highlighting neighboring and ambiguous assignments.\ud \ud Conclusions\ud The MetaboLab software is an integrated software package for NMR data processing and analysis, closely linked to the previously developed NMRLab software. It includes tools for batch processing and gives access to a wealth of algorithms available in the MATLAB framework. Algorithms within MetaboLab help to optimize the flow of metabolomics data preparation for statistical analysis. The combination of an intuitive graphical user interface along with advanced data processing algorithms facilitates the use of MetaboLab in a broader metabolomics context.\ud \u

    Ecological Aesthetics: new spaces, directions, and potentials

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    In this final section of the Handbook, we turn to ecological aesthetics in response to radical changes in both the nature of childhood and the nature of nature in the contemporary world. Artistic and aesthetic approaches have become increasingly relevant as children encounter a world typified by the acceleration of social, technological, and environmental change, and the mutually reinforcing conditions of planetary instability, inequality, and precarity. Anthropogenic climate change, the mass extinction of plant and animal life, and the chemical contamination of air, food, soil, and water resources are transforming not only what we might think of as “the environment”, but also the aesthetic qualities and environmental sensibilities that constitute the experience of being alive. For many scholars these changing conditions of Earthly life have taken on the name of ‘Anthropocene’, an epoch defined by the total imbrication of human life with more than human planetary systems and technologies. The authors in this section take up ecological aesthetics as a relational, experimental, and theoretically adventurous field which aims to grasp the experiential qualities of life under these changing conditions, and to imagine alternatives. With chapters focusing on the role of movement, nature-study, poetry, pattern, sense-awareness, and the creation of experimental works of art, this section highlights interdisciplinary research and pedagogy which attends to richly textured compositions of childhoodnature experience through a diverse range of material, social and conceptual practices. In drawing together a range of Indigenous, speculative, sensory, cultural, empirical, and artistic approaches, the range of chapters collected in this section attests to the diversity and emergent shaping of ecological aesthetics as a field that is still very much in the making

    A dusty pinwheel nebula around the massive star WR 104

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    Wolf-Rayet (WR) stars are luminous massive blue stars thought to be immediate precursors to the supernova terminating their brief lives. The existence of dust shells around such stars has been enigmatic since their discovery some 30 years ago; the intense radiation field from the star should be inimical to dust survival. Although dust-creation models, including those involving interacting stellar winds from a companion star, have been put forward, high-resolution observations are required to understand this phenomena. Here we present resolved images of the dust outflow around Wolf-Rayet WR 104, obtained with novel imaging techniques, revealing detail on scales corresponding to about 40 AU at the star. Our maps show that the dust forms a spatially confined stream following precisely a linear (or Archimedian) spiral trajectory. Images taken at two separate epochs show a clear rotation with a period of 220 +/- 30 days. Taken together, these findings prove that a binary star is responsible for the creation of the circumstellar dust, while the spiral plume makes WR 104 the prototype of a new class of circumstellar nebulae unique to interacting wind systems.Comment: 7 pages, 2 figures, Appearing in Nature (1999 April 08

    Pengujian Dan Analisis Performansi Model Turbin Angin Tipe Poros Silang Kapasitas Daya 10 W

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    ABSTRAK Pemanfaatan energi angin dengan menggunakan turbin angin terus meningkat sebagai alat konversi energi yang sudah dikenal sejak dahulu. Jenis turbin angin yang sudah lama dikenal yaitu turbin angin poros vertikal dan turbin angin poros horizontal. Turbin ini didesain untuk menyerap energi angin yang datang secara horizontal sedangkan dalam kenyataannya angin sering bergerak secara acak. Oleh karena itu dikembangkan jenis turbin baru yaitu turbin angin tipe poros silang. Turbin angin tipe poros silang ini didesain dapat menyerap energi angin yang datang secara acak. Model turbin angin tipe poros silang ini terdiri dari 5 buah sudu vertikal dan 6 buah sudu horizontal. Pengujian turbin angin meliputi pengukuran kecepatan angin, kecepatan putar poros, tegangan dan arus listrik. Uji kinerja dilakukan pada kecepatan angin yang konstan. Selama pengujian, sudut pitch sudu horizontal divariasikan dari 25° hingga 40° dengan kecepatan angin 4,1 m/s dan 5,2 m/s. Hasil penelitian menunjukan bahwa daya keluaran dan efisiensi turbin angin dipengaruhi oleh sudut pitch sudu horizontal, slip pada sistem transmisi dan beban material pada turbin angin. Kecepatan putar poros maksimum sebesar 178 rpm dihasilkan pada sudut pitch sudu horizontal 40° dengan kecepatan angin 5,2 m/s. Koefisien daya maksimum terbesar didapat sebesar 7,1% pada kecepatan angin 4,1 m/s dengan sudut pitch sudu horizontal 40° dan daya listrik maksimum keluaran dari generator sebesar 2,88 W pada sudut pitch 40° dengan kecepatan angin 5,2 m/s. Kata Kunci: Turbin angin tipe poros silang, Sudut pitch sudu horizontal, Koefisien daya

    Prevalence, Concordance, and Heritability of Vitreomacular Interface Abnormalities in a Twin Study

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    PURPOSE: The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the prevalence case wise concordance between monozygotic and dizygotic twin pairs, and heritability of common VMI abnormalities, including epiretinal membrane (ERM), posterior vitreous detachment (PVD), vitreomacular adhesion (VMA), vitreomacular traction (VMT), lamellar macular holes (LMHs), and full-thickness macular holes (FTMHs). METHODS: This is a single-center, cross-sectional classical twin study of 3406 TwinsUK participants over the age of 40 years who underwent spectral domain macular optical coherence tomography (SD-OCT) scans which were graded for signs of VMI abnormalities. Case wise concordance was calculated and the heritability of each VMI abnormality was estimated using OpenMx structural equation modeling. RESULTS: In this population (mean age = 62.0 years [SD = 10.4 years], range = 40–89 years) the overall prevalence of ERM was 15.6% (95% confidence interval [CI] = 14.4–16.9) and increased with age, posterior vitreous detachment affected 21.3% (20.0–22.7), and VMA was diagnosed in 11.8% (10.8–13.0). Monozygotic twins were more concordant for all traits than dizygotic twins, and age, spherical equivalent refraction (SER), and lens status-adjusted heritability was estimated at 38.9% (95% CI = 33.6–52.8) for ERM, 53.2% (95% CI = 41.8–63.2) for PVD, and 48.1% (95% CI = 33.6–58) for VMA. CONCLUSIONS: Common VMI abnormalities are heritable and therefore have an underlying genetic component. Given the sight-threatening potential of VMI abnormalities, further genetic studies, such as genomewide association studies, would be useful to identify genes and pathways implicated in their pathogenesis
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