105 research outputs found
A Reference-Free Algorithm for Computational Normalization of Shotgun Sequencing Data
Deep shotgun sequencing and analysis of genomes, transcriptomes, amplified
single-cell genomes, and metagenomes has enabled investigation of a wide range
of organisms and ecosystems. However, sampling variation in short-read data
sets and high sequencing error rates of modern sequencers present many new
computational challenges in data interpretation. These challenges have led to
the development of new classes of mapping tools and {\em de novo} assemblers.
These algorithms are challenged by the continued improvement in sequencing
throughput. We here describe digital normalization, a single-pass computational
algorithm that systematizes coverage in shotgun sequencing data sets, thereby
decreasing sampling variation, discarding redundant data, and removing the
majority of errors. Digital normalization substantially reduces the size of
shotgun data sets and decreases the memory and time requirements for {\em de
novo} sequence assembly, all without significantly impacting content of the
generated contigs. We apply digital normalization to the assembly of microbial
genomic data, amplified single-cell genomic data, and transcriptomic data. Our
implementation is freely available for use and modification
Exploring the Roles of Spectral Detail and Intonation Contour in Speech Intelligibility:An fMRI Study
The melodic contour of speech forms an important perceptual aspect of tonal and nontonal languages and an important limiting factor on the intelligibility of speech heard through a cochlear implant. Previous work exploring the neural correlates of speech comprehension identified a left-dominant pathway in the temporal lobes supporting the extraction of an intelligible linguistic message, whereas the right anterior temporal lobe showed an overall preference for signals clearly conveying dynamic pitch information. The current study combined modulations of overall intelligibility (through vocoding and spectral inversion) with a manipulation of pitch contour (normal vs. falling) to investigate the processing of spoken sentences in functional MRI. Our overall findings replicate and extend those of Scott et al., whereas greater sentence intelligibility was predominately associated with increased activity in the left STS, the greatest response to normal sentence melody was found right superior temporal gyrus. These data suggest a spatial distinction between brain areas associated with intelligibility and those involved in the processing of dynamic pitch information in speech. By including a set of complexity-matched unintelligible conditions created by spectral inversion, this is additionally the first study reporting a fully factorial exploration of spectrotemporal complexity and spectral inversion as they relate to the neural processing of speech intelligibility. Perhaps surprisingly, there was no evidence for an interaction between the two factorsâwe discuss the implications for the processing of sound and speech in the dorsolateral temporal lobes
The relationship between adverse neighborhood socioeconomic context and HIV continuum of care outcomes in a diverse HIV clinic cohort in the Southern United States
Retention in care and viral suppression are critical to delaying HIV progression and reducing transmission. Neighborhood socioeconomic context (NSEC) may affect HIV care receipt. We therefore assessed NSEC's impact on retention and viral suppression in a diverse HIV clinical cohort. HIV-positive adults with â„1 visit at the Vanderbilt Comprehensive Care Clinic and 5-digit ZIP code tabulation area (ZCTA) information between 2008 and 2012 contributed. NSEC z-score indices used neighborhood-level socioeconomic indicators for poverty, education, labor-force participation, proportion of males, median age, and proportion of residents of black race by ZCTA. Retention was defined as â„2 HIV care visits per calendar year, >90 days apart. Viral suppression was defined as an HIV-1 RNA <200 copies/mL at last measurement per calendar year. Modified Poisson regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI). Among 2272 and 2541 adults included for retention and viral suppression analyses, respectively, median age and CD4 count at enrollment were approximately 38 (1st and 3rd quartile: 30, 44) years and 351 (176, 540) cells/ÎŒL, respectively, while 24% were female, and 39% were black. Across 243 ZCTAs, median NSEC z-score was 0.09 (-0.66, 0.48). Overall, 79% of person-time contributed was retained and 74% was virally suppressed. In adjusted models, NSEC was not associated with retention, though being in the 4th vs. 1st NSEC quartile was associated with lack of viral suppression (RRâ=â0.88; 95% CI: 0.80-0.97). Residing in the most adverse NSEC was associated with lack of viral suppression. Future studies are needed to confirm this finding
Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery
Inactivation of eukaryotic 2-Cys peroxiredoxins (Prxs) by hyperoxidation has been proposed to promote accumulation of hydrogen peroxide (H2O2) for redox-dependent signaling events. We examined the oxidation and oligomeric states of PrxI and -II in epithelial cells during mitogenic signaling and in response to fluxes of H2O2. During normal mitogenic signaling, hyperoxidation of PrxI and -II was not detected. In contrast, H2O2-dependent cell cycle arrest was correlated with hyperoxidation of PrxII, which resulted in quantitative recruitment of âŒ66- and âŒ140-kD PrxII complexes into large filamentous oligomers. Expression of cyclin D1 and cell proliferation did not resume until PrxII-SO2H was reduced and native PrxII complexes were regenerated. Ectopic expression of PrxI or -II increased Prx-SO2H levels in response to oxidant exposure and failed to protect cells from arrest. We propose a model in which Prxs function as peroxide dosimeters in subcellular processes that involve redox cycling, with hyperoxidation controlling structural transitions that alert cells of perturbations in peroxide homeostasis
The low-order wavefront sensor for the PICTURE-C mission
The PICTURE-C mission will fly a 60 cm off-axis unobscured telescope and two high-contrast coronagraphs in successive high-altitude balloon flights with the goal of directly imaging and spectrally characterizing visible scattered light from exozodiacal dust in the interior 1-10 AU of nearby exoplanetary systems. The first flight in 2017 will use a 10[superscript -4] visible nulling coronagraph (previously flown on the PICTURE sounding rocket) and the second flight in 2019 will use a 10[superscript -7] vector vortex coronagraph. A low-order wavefront corrector (LOWC) will be used in both flights to remove time-varying aberrations from the coronagraph wavefront. The LOWC actuator is a 76-channel high-stroke deformable mirror packaged on top of a tip-tilt stage. This paper will detail the selection of a complementary high-speed, low-order wavefront sensor (LOWFS) for the mission. The relative performance and feasibility of several LOWFS designs will be compared including the Shack-Hartmann, Lyot LOWFS, and the curvature sensor. To test the different sensors, a model of the time-varying wavefront is constructed using measured pointing data and inertial dynamics models to simulate optical alignment perturbations and surface deformation in the balloon environment.United States. National Aeronautics and Space Administration (Grant NNX15AG23G S01
The low-order wavefront sensor for the PICTURE-C mission
The PICTURE-C mission will fly a 60 cm off-axis unobscured telescope and two high-contrast coronagraphs in successive high-altitude balloon flights with the goal of directly imaging and spectrally characterizing visible scattered light from exozodiacal dust in the interior 1-10 AU of nearby exoplanetary systems. The first flight in 2017 will use a 10^(-4) visible nulling coronagraph (previously flown on the PICTURE sounding rocket) and the second flight in 2019 will use a 10^(-7) vector vortex coronagraph. A low-order wavefront corrector (LOWC) will be used in both flights to remove time-varying aberrations from the coronagraph wavefront. The LOWC actuator is a 76-channel high-stroke deformable mirror packaged on top of a tip-tilt stage. This paper will detail the selection of a complementary high-speed, low-order wavefront sensor (LOWFS) for the mission. The relative performance and feasibility of several LOWFS designs will be compared including the Shack-Hartmann, Lyot LOWFS, and the curvature sensor. To test the different sensors, a model of the time-varying wavefront is constructed using measured pointing data and inertial dynamics models to simulate optical alignment perturbations and surface deformation in the balloon environment
Detectors for the James Webb Space Telescope Near-Infrared Spectrograph I: Readout Mode, Noise Model, and Calibration Considerations
We describe how the James Webb Space Telescope (JWST) Near-Infrared
Spectrograph's (NIRSpec's) detectors will be read out, and present a model of
how noise scales with the number of multiple non-destructive reads
sampling-up-the-ramp. We believe that this noise model, which is validated
using real and simulated test data, is applicable to most astronomical
near-infrared instruments. We describe some non-ideal behaviors that have been
observed in engineering grade NIRSpec detectors, and demonstrate that they are
unlikely to affect NIRSpec sensitivity, operations, or calibration. These
include a HAWAII-2RG reset anomaly and random telegraph noise (RTN). Using real
test data, we show that the reset anomaly is: (1) very nearly noiseless and (2)
can be easily calibrated out. Likewise, we show that large-amplitude RTN
affects only a small and fixed population of pixels. It can therefore be
tracked using standard pixel operability maps.Comment: 55 pages, 10 figure
Automated brain tumour detection and segmentation using superpixel-based extremely randomized trees in FLAIR MRI
PURPOSE: We propose a fully automated method for detection and segmentation of the abnormal tissue associated with brain tumour (tumour core and oedema) from Fluid- Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI). METHODS: The method is based on superpixel technique and classification of each superpixel. A number of novel image features including intensity-based, Gabor textons, fractal analysis and curvatures are calculated from each superpixel within the entire brain area in FLAIR MRI to ensure a robust classification. Extremely randomized trees (ERT) classifier is compared with support vector machine (SVM) to classify each superpixel into tumour and non-tumour. RESULTS: The proposed method is evaluated on two datasets: (1) Our own clinical dataset: 19 MRI FLAIR images of patients with gliomas of grade II to IV, and (2) BRATS 2012 dataset: 30 FLAIR images with 10 low-grade and 20 high-grade gliomas. The experimental results demonstrate the high detection and segmentation performance of the proposed method using ERT classifier. For our own cohort, the average detection sensitivity, balanced error rate and the Dice overlap measure for the segmented tumour against the ground truth are 89.48Â %, 6Â % and 0.91, respectively, while, for the BRATS dataset, the corresponding evaluation results are 88.09Â %, 6Â % and 0.88, respectively. CONCLUSIONS: This provides a close match to expert delineation across all grades of glioma, leading to a faster and more reproducible method of brain tumour detection and delineation to aid patient management
An improved pig reference genome sequence to enable pig genetics and genomics research.
BACKGROUND: The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model given its similarity in size, anatomy, physiology, metabolism, pathology, and pharmacology to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete, and unresolved redundancies, short-range order and orientation errors, and associated misassembled genes limited its utility. RESULTS: We present 2 annotated highly contiguous chromosome-level genome assemblies created with more recent long-read technologies and a whole-genome shotgun strategy, 1 for the same Duroc female (Sscrofa11.1) and 1 for an outbred, composite-breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. CONCLUSIONS: These highly contiguous assemblies plus annotation of a further 11 short-read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs
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