516 research outputs found

    Correcting for sequence biases in present/absent calls

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    Correction of non-specific binding for both PM and MM probes using probe-sequence models can partially remove the probe-sequence bias in Affymetrix microarray experiments and result in better performance of the MAS 5.0 algorithm

    Estimation and correction of non-specific binding in a large-scale spike-in experiment

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    A combined statistical analysis using the MAS5 PM-MM, GC-NSB and PDNN methods to generate probeset values from microarray data results in an improved ability to detect differential expression and estimates of false discovery rates compared with the individual methods

    Precision Epoch of Reionization studies with next-generation CMB experiments

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    Future arcminute resolution polarization data from ground-based Cosmic Microwave Background (CMB) observations can be used to estimate the contribution to the temperature power spectrum from the primary anisotropies and to uncover the signature of reionization near ℓ=1500\ell=1500 in the small angular-scale temperature measurements. Our projections are based on combining expected small-scale E-mode polarization measurements from Advanced ACTPol in the range 300<ℓ<3000300<\ell<3000 with simulated temperature data from the full Planck mission in the low and intermediate ℓ\ell region, 2<ℓ<20002<\ell<2000. We show that the six basic cosmological parameters determined from this combination of data will predict the underlying primordial temperature spectrum at high multipoles to better than 1%1\% accuracy. Assuming an efficient cleaning from multi-frequency channels of most foregrounds in the temperature data, we investigate the sensitivity to the only residual secondary component, the kinematic Sunyaev-Zel'dovich (kSZ) term. The CMB polarization is used to break degeneracies between primordial and secondary terms present in temperature and, in effect, to remove from the temperature data all but the residual kSZ term. We estimate a 15σ15 \sigma detection of the diffuse homogeneous kSZ signal from expected AdvACT temperature data at ℓ>1500\ell>1500, leading to a measurement of the amplitude of matter density fluctuations, σ8\sigma_8, at 1%1\% precision. Alternatively, by exploring the reionization signal encoded in the patchy kSZ measurements, we bound the time and duration of the reionization with σ(zre)=1.1\sigma(z_{\rm re})=1.1 and σ(Δzre)=0.2\sigma(\Delta z_{\rm re})=0.2. We find that these constraints degrade rapidly with large beam sizes, which highlights the importance of arcminute-scale resolution for future CMB surveys.Comment: 10 pages, 10 figure

    A Dystrophin Exon-52 Deleted Miniature Pig Model of Duchenne Muscular Dystrophy and Evaluation of Exon Skipping

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    Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder caused by mutations in the DMD gene and the subsequent lack of dystrophin protein. Recently, phosphorodiamidate morpholino oligomer (PMO)-antisense oligonucleotides (ASOs) targeting exon 51 or 53 to reestablish the DMD reading frame have received regulatory approval as commercially available drugs. However, their applicability and efficacy remain limited to particular patients. Large animal models and exon skipping evaluation are essential to facilitate ASO development together with a deeper understanding of dystrophinopathies. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, we generated a Yucatan miniature pig model of DMD with an exon 52 deletion mutation equivalent to one of the most common mutations seen in patients. Exon 52-deleted mRNA expression and dystrophin deficiency were confirmed in the skeletal and cardiac muscles of DMD pigs. Accordingly, dystrophin-associated proteins failed to be recruited to the sarcolemma. The DMD pigs manifested early disease onset with severe bodywide skeletal muscle degeneration and with poor growth accompanied by a physical abnormality, but with no obvious cardiac phenotype. We also demonstrated that in primary DMD pig skeletal muscle cells, the genetically engineered exon-52 deleted pig DMD gene enables the evaluation of exon 51 or 53 skipping with PMO and its advanced technology, peptide-conjugated PMO. The results show that the DMD pigs developed here can be an appropriate large animal model for evaluating in vivo exon skipping efficacy

    Evolutionary conservation of regulated longevity assurance mechanisms

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    Short abstract: A multi-level cross-species comparative analysis of gene-expression changes accompanying increased longevity in mutant nematodes, fruit flies and mice with reduced insulin/IGF-1 signaling revealed candidate conserved mechanisms
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