578 research outputs found

    Cerulean: A hybrid assembly using high throughput short and long reads

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    Genome assembly using high throughput data with short reads, arguably, remains an unresolvable task in repetitive genomes, since when the length of a repeat exceeds the read length, it becomes difficult to unambiguously connect the flanking regions. The emergence of third generation sequencing (Pacific Biosciences) with long reads enables the opportunity to resolve complicated repeats that could not be resolved by the short read data. However, these long reads have high error rate and it is an uphill task to assemble the genome without using additional high quality short reads. Recently, Koren et al. 2012 proposed an approach to use high quality short reads data to correct these long reads and, thus, make the assembly from long reads possible. However, due to the large size of both dataset (short and long reads), error-correction of these long reads requires excessively high computational resources, even on small bacterial genomes. In this work, instead of error correction of long reads, we first assemble the short reads and later map these long reads on the assembly graph to resolve repeats. Contribution: We present a hybrid assembly approach that is both computationally effective and produces high quality assemblies. Our algorithm first operates with a simplified version of the assembly graph consisting only of long contigs and gradually improves the assembly by adding smaller contigs in each iteration. In contrast to the state-of-the-art long reads error correction technique, which requires high computational resources and long running time on a supercomputer even for bacterial genome datasets, our software can produce comparable assembly using only a standard desktop in a short running time.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

    Creation and evaluation of full-text literature-derived, feature-weighted disease models of genetically determined developmental disorders

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    There are >2500 different genetically determined developmental disorders (DD), which, as a group, show very high levels of both locus and allelic heterogeneity. This has led to the wide-spread use of evidence-based filtering of genome-wide sequence data as a diagnostic tool in DD. Determining whether the association of a filtered variant at a specific locus is a plausible explanation of the phenotype in the proband is crucial and commonly requires extensive manual literature review by both clinical scientists and clinicians. Access to a database of weighted clinical features extracted from rigorously curated literature would increase the efficiency of this process and facilitate the development of robust phenotypic similarity metrics. However, given the large and rapidly increasing volume of published information, conventional biocuration approaches are becoming impractical. Here, we present a scalable, automated method for the extraction of categorical phenotypic descriptors from the full-text literature. Papers identified through literature review were downloaded and parsed using the Cadmus custom retrieval package. Human Phenotype Ontology terms were extracted using MetaMap, with 76–84% precision and 65–73% recall. Mean terms per paper increased from 9 in title + abstract, to 68 using full text. We demonstrate that these literature-derived disease models plausibly reflect true disease expressivity more accurately than widely used manually curated models, through comparison with prospectively gathered data from the Deciphering Developmental Disorders study. The area under the curve for receiver operating characteristic (ROC) curves increased by 5–10% through the use of literature-derived models. This work shows that scalable automated literature curation increases performance and adds weight to the need for this strategy to be integrated into informatic variant analysis pipelines. Database URL: https://doi.org/10.1093/database/baac03

    Association between dendritic lamellar bodies and complex spike synchrony in the olivocerebellar system

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    Dendritic lamellar bodies have been reported to be associated with dendrodendritic gap junctions. In the present study we investigated this association at both the morphological and electrophysiological level in the olivocerebellar system. Because cerebellar GABAergic terminals are apposed to olivary dendrites coupled by gap junctions, and because lesions of cerebellar nuclei influence the coupling between neurons in the inferior olive, we postulated that if lamellar bodies and gap junctions are related, then the densities of both structures will change together when the cerebellar input is removed. Lesions of the cerebellar nuclei in rats and rabbits resulted in a reduction of the density of lamellar bodies, the number of lamellae per lamellar body, and the density of gap junctions in the inferior olive, whereas the number of olivary neurons was not significantly reduced. The association between lamellar bodies and electrotonic coupling was evaluated electrophysiologically in alert rabbits by comparing the occurrence of complex spike synchrony in different Purkinje cell zones of the flocculus that receive their climbing fibers from olivary subnuclei with different densities of lamellar bodies. The complex spike synchrony of Purkinje cell pairs, that receive their climbing fibers from an olivary subnucleus with a high density of lamellar bodies, was significantly higher than that of Purkinje cells, that receive their climbing fibers from a subnucleus with a low density of lamellar bodies. To investigate whether the complex spike synchrony is related to a possible synchrony between simple spikes, we recorded simultaneously the complex spike and simple spike responses of Purkinje cell pairs during natural visual stimulation. Synchronous simple spike responses did occur, and this synchrony tended to increase as the synchrony between the complex spikes increased. This relation raises the possibility that synchronously activated climbing fibers evoke their effects in part via the simple spike response of Purkinje cells. The present results indicate that dendritic lamellar bodies and dendrodendritic gap junctions can be downregulated concomitantly, and that the density of lamellar bodies in different olivary subdivisions is correlated with the degree of synchrony of their climbing fiber activity. Therefore these data support the hypothesis that dendritic lamellar bodies can be associated with dendrodendritic gap junctions. Considering that the density of dedritic lamellar bodies in the inferior olive is higher than in any other area of the brain, this conclusion implies that electrotonic coupling is important for the function of the olivocerebellar system

    Cultural intermediaries and the circuit of culture : the digital ambassadors project in Johannesburg, South Africa

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    Abstract: The question raised by Cheney and Christensen (2001) as to “what a non-Western, nonmanagerial and non-rationalist form of public relations will look like” (p.182), together with the call made by Gregory (2014) for public relations practitioners (PRPs) to be active social change agents, motivated this paper. The aim of this research is to follow a culture-centred approach and apply the circuit of culture (Curtin & Gaither, 2005) to investigate the meanings that young people (aged 18 to 34), as cultural intermediaries, ascribe to their participation in a digital empowerment project implemented by the City of Johannesburg, South Africa. This research forms part of a larger, ongoing multi-disciplinary research project..

    Representation of the Community Earth System Model (CESM1) CAM4-chem within the Chemistry-Climate Model Initiative (CCMI)

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    The Community Earth System Model (CESM1) CAM4-chem has been used to perform the Chemistry Climate Model Initiative (CCMI) reference and sensitivity simulations. In this model, the Community Atmospheric Model version 4 (CAM4) is fully coupled to tropospheric and stratospheric chemistry. Details and specifics of each configuration, including new developments and improvements are described. CESM1 CAM4-chem is a low-top model that reaches up to approximately 40km and uses a horizontal resolution of 1.9° latitude and 2.5° longitude. For the specified dynamics experiments, the model is nudged to Modern-Era Retrospective Analysis for Research and Applications (MERRA) reanalysis. We summarize the performance of the three reference simulations suggested by CCMI, with a focus on the last 15 years of the simulation when most observations are available. Comparisons with selected data sets are employed to demonstrate the general performance of the model. We highlight new data sets that are suited for multi-model evaluation studies. Most important improvements of the model are the treatment of stratospheric aerosols and the corresponding adjustments for radiation and optics, the updated chemistry scheme including improved polar chemistry and stratospheric dynamics and improved dry deposition rates. These updates lead to a very good representation of tropospheric ozone within 20% of values from available observations for most regions. In particular, the trend and magnitude of surface ozone is much improved compared to earlier versions of the model. Furthermore, stratospheric column ozone of the Southern Hemisphere in winter and spring is reasonably well represented. All experiments still underestimate CO most significantly in Northern Hemisphere spring and show a significant underestimation of hydrocarbons based on surface observations

    Three-dimensional digital reconstruction of human placental villus architecture in normal and complicated pregnancies.

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    Objective: This study aimed to examine the use of digital technology in the three-dimensional reconstruction of human placentas. Study design: Placentas obtained at term elective caesarean section were sampled, formalin-fixed and embedded in paraffin. Two hundred 5 mm consecutive sections were cut from each specimen and the resultant slides stained with haematoxylin and eosin. Slides were then scanned and the digitised images reconstructed using customised software. Results: Three-dimensional reconstructions were successfully achieved in placentas from normal pregnancies and those complicated by pre-eclampsia, growth restriction, and gestational diabetes. Marked morphological differences were readily identifiable, most clearly in the stem villus architecture. Conclusion: This method is an emerging research tool for examining placental histoarchitecture at high resolution and gaining clinically relevant insight into the placental pathology allied to pregnancy complications such as PET, IUGR and GD

    Linear Responses in Time-dependent Hartree-Fock-Bogoliubov Method with Gogny Interaction

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    A numerical method to integrate the time-dependent Hartree-Fock Bogoliubov (TDHFB) equations with Gogny interaction is proposed. The feasibility of the TDHFB code is illustrated by the conservation of the energy, particle numbers, and center-of-mass in the small amplitude vibrations of oxygen 20. The TDHFB code is applied to the isoscalar quadrupole and/or isovector dipole vibrations in the linear (small amplitude) region in oxygen isotopes (masses A = 18,20,22 and 24), titanium isotopes (A = 44,50,52 and 54), neon isotope (A = 26), and magnesium isotopes (A = 24 and 34). The isoscalar quadrupole and isovector dipole strength functions are calculated from the expectation values of the isoscalar quadrupole and isovector dipole moments.Comment: 10 pages, 13 figure

    Natural disturbances and the physiognomy of pine savannas : A phenomenological model

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    Abstract. Question: The decline of the Pinus palustris ecosystems has resulted from anthropogenic influences, such as conversion to pine plantation forestry, agriculture and land development, all of which are closely related to increases in human populations. Other effects, however, have arisen from alterations in disturbance regimes that maintain the structure and function of these ecosystems. How have alterations of the disturbance regime altered the physiognomy of ‘old-growth’ stands, and what are the implications for ecosystem conservation and restoration? Methods: In contrast to models that emphasize close interactions among the vertically complex strata, we develop a conceptual phenomenological model for the physiognomic structure of Pinus palustris stands. We relate two natural disturbances (tropical storms and fire) that affect different stages of the life cycle to different aspects of the physiognomic structure. We then compare overstorey stand structure and ground cover composition of two old-growth longleaf stands near the extremes of different composite disturbance regimes: the Wade Tract (frequent hurricanes and fire) and the Boyd Tract (infrequent hurricanes and long-term fire exclusion). Results: We predict that tropical storms and fires have different effects on stand physiognomy. Tropical storms are periodic, and sometimes intense, whereas fires are more frequent and less intense. Hurricanes directly influence the overstorey via wind-caused damage and mortality, and indirectly influence the herb layer by altering the spatial distribution of shading and litter accumulation. Fire exerts direct effects on juvenile stages and indirect effects on the herb layer via fine fuel consumption and selective mortality of potential competitors of P. palustris juveniles. These differences in effects of disturbances can result in widely different physiognomies for P. palustris stands. Finally, some global climate change scenarios have suggested that changes may occur in tropical storm and fire regimes, altering frequency and severity. Such changes may greatly affect pine stands, and ultimately entire pine savanna ecosystems. Conclusions: Our phenomenological model of disturbance regimes in Pinus palustris old-growth produces very different physiognomies for different disturbances regimes that reflect natural process and human management actions. This model can be used to derive restoration strategies for pine savannas that are linked to reinstitution of important ecological processes rather than specific physiognomic states

    Search for Global Dipole Enhancements in the HiRes-I Monocular Data above 10^{18.5} eV

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    Several proposed source models for Ultra-High Energy Cosmic Rays (UHECRs) consist of dipole distributions oriented towards major astrophysical landmarks such as the galactic center, M87, or Centaurus A. We use a comparison between real data and simulated data to show that the HiRes-I monocular data for energies above 10^{18.5} eV is, in fact, consistent with an isotropic source model. We then explore methods to quantify our sensitivity to dipole source models oriented towards the Galactic Center, M87, and Centaurus A.Comment: 17 pages, 31 figure
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