385 research outputs found
New insights into the genetic control of gene expression using a Bayesian multi-tissue approach.
The majority of expression quantitative trait locus (eQTL) studies have been carried out in single tissues or cell types, using methods that ignore information shared across tissues. Although global analysis of RNA expression in multiple tissues is now feasible, few integrated statistical frameworks for joint analysis of gene expression across tissues combined with simultaneous analysis of multiple genetic variants have been developed to date. Here, we propose Sparse Bayesian Regression models for mapping eQTLs within individual tissues and simultaneously across tissues. Testing these on a set of 2,000 genes in four tissues, we demonstrate that our methods are more powerful than traditional approaches in revealing the true complexity of the eQTL landscape at the systems-level. Highlighting the power of our method, we identified a two-eQTL model (cis/trans) for the Hopx gene that was experimentally validated and was not detected by conventional approaches. We showed common genetic regulation of gene expression across four tissues for ∼27% of transcripts, providing >5 fold increase in eQTLs detection when compared with single tissue analyses at 5% FDR level. These findings provide a new opportunity to uncover complex genetic regulatory mechanisms controlling global gene expression while the generality of our modelling approach makes it adaptable to other model systems and humans, with broad application to analysis of multiple intermediate and whole-body phenotypes
Comparison of Different Parallel Implementations of the 2+1-Dimensional KPZ Model and the 3-Dimensional KMC Model
We show that efficient simulations of the Kardar-Parisi-Zhang interface
growth in 2 + 1 dimensions and of the 3-dimensional Kinetic Monte Carlo of
thermally activated diffusion can be realized both on GPUs and modern CPUs. In
this article we present results of different implementations on GPUs using CUDA
and OpenCL and also on CPUs using OpenCL and MPI. We investigate the runtime
and scaling behavior on different architectures to find optimal solutions for
solving current simulation problems in the field of statistical physics and
materials science.Comment: 14 pages, 8 figures, to be published in a forthcoming EPJST special
issue on "Computer simulations on GPU
An MRI evaluation of grey matter damage in African Americans with MS
Objective: Multiple sclerosis (MS) is less prevalent in African Americans (AAs) than Caucasians (CAs) but in the former the disease course tends to be more severe. In order to clarify the MRI correlates of disease severity in AAs, we performed a multimodal brain MRI study to comprehensively assess the extent of grey matter (GM) damage and the degree of functional adaptation to structural damage in AAs with MS. Methods: In this cross-sectional study, we characterized GM damage in terms of focal lesions and volume loss and functional adaptation during the execution of a simple motor task on a sample of 20 AAs and 20 CAs with MS and 20 healthy controls (CTRLs). Results: In AAs, we observed a wider range of EDSS scores than CAs, with multisystem involvement being more likely in AAs (p < 0.01). While no significant differences were detected in lesion loads and global brain volumes, AAs showed regional atrophy in the posterior lobules of cerebellum, temporo-occipital and frontal regions in comparison with CAs (p < 0.01), with cerebellar atrophy being the best metric in differentiating AAs from CAs (p = 0.007, AUC = 0.96 and p = 0.005, AUC = 0.96, respectively for right and left cerebellar clusters). In AAs, the functional analysis of cortical activations showed an increase in task-related activation of areas involved in high level processing and a decreased activation in the medial prefrontal cortex compared to CAs. Interpretation: In our study, the direct comparison of AAs and CAs points to cerebellar atrophy as the main difference between subgroups
Translational regulation shapes the molecular landscape of complex disease phenotypes.
The extent of translational control of gene expression in mammalian tissues remains largely unknown. Here we perform genome-wide RNA sequencing and ribosome profiling in heart and liver tissues to investigate strain-specific translational regulation in the spontaneously hypertensive rat (SHR/Ola). For the most part, transcriptional variation is equally apparent at the translational level and there is limited evidence of translational buffering. Remarkably, we observe hundreds of strain-specific differences in translation, almost doubling the number of differentially expressed genes. The integration of genetic, transcriptional and translational data sets reveals distinct signatures in 3'UTR variation, RNA-binding protein motifs and miRNA expression associated with translational regulation of gene expression. We show that a large number of genes associated with heart and liver traits in human genome-wide association studies are primarily translationally regulated. Capturing interindividual differences in the translated genome will lead to new insights into the genes and regulatory pathways underlying disease phenotypes
Phrenologyand the Insanity Defence: Medical Jurisprudence in the McNaughtan Trial
This thesis argues that phrenology shaped the defence argument in the McNaughtan trial. The role of this now-discredited science exemplifies the negotiation of scientific, legal and lay knowledge in the early nineteenth century, at a time when science was challenging the primacy of lay understandings of insanity. Phrenological ideas allowed the defence to privilege medical opinion over lay opinion, and propose a model of the mind that could account for McNaughtan’s insanity. This was possible because the medical and professional communities accepted some elements of the science. They applied these principles when explaining and verifying insanity in a courtroom setting
Influence of vortex-vortex interaction on critical currents across low-angle grain boundaries in YBa2Cu3O7-delta thin films
Low-angle grain boundaries with misorientation angles theta < 5 degrees in
optimally doped thin films of YBCO are investigated by magnetooptical imaging.
By using a numerical inversion scheme of Biot-Savart's law the critical current
density across the grain boundary can be determined with a spatial resolution
of about 5 micrometers. Detailed investigation of the spatially resolved flux
density and current density data shows that the current density across the
boundary varies with varying local flux density. Combining the corresponding
flux and current pattern it is found that there exists a universal dependency
of the grain boundary current on the local flux density. A change in the local
flux density means a variation in the flux line-flux line distance. With this
knowledge a model is developped that explains the flux-current relation by
means of magnetic vortex-vortex interaction.Comment: 7 pages, 14 figure
A weakly stable algorithm for general Toeplitz systems
We show that a fast algorithm for the QR factorization of a Toeplitz or
Hankel matrix A is weakly stable in the sense that R^T.R is close to A^T.A.
Thus, when the algorithm is used to solve the semi-normal equations R^T.Rx =
A^Tb, we obtain a weakly stable method for the solution of a nonsingular
Toeplitz or Hankel linear system Ax = b. The algorithm also applies to the
solution of the full-rank Toeplitz or Hankel least squares problem.Comment: 17 pages. An old Technical Report with postscript added. For further
details, see http://wwwmaths.anu.edu.au/~brent/pub/pub143.htm
HIV-1 Drug Resistance Emergence among Breastfeeding Infants Born to HIV-Infected Mothers during a Single-Arm Trial of Triple-Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission: A Secondary Analysis
Analysis of a substudy of the Kisumu breastfeeding trial by Clement Zeh and colleagues reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs
Strongly linked current flow in polycrystalline forms of the new superconductor MgB2
The discovery of superconductivity at 39 K in MgB2[1] raises many issues. One
of the central questions is whether this new superconductor resembles a
high-temperature-cuprate superconductor or a low-temperature metallic
superconductor in terms of its current carrying characteristics in applied
magnetic fields. In spite of the very high transition temperatures of the
cuprate superconductors, their performance in magnetic fields has several
drawbacks[2]. Their large anisotropy restricts high bulk current densities to
much less than the full magnetic field-temperature (H-T) space over which
superconductivity is found. Further, weak coupling across grain boundaries
makes transport current densities in untextured polycrystalline forms low and
strongly magnetic field sensitive[3,4]. These studies of MgB2 address both
issues. In spite of the multi-phase, untextured, nano-scale sub-divided nature
of our samples, supercurrents flow throughout without the strong sensitivity to
weak magnetic fields characteristic of Josephson-coupled grains[3].
Magnetization measurements over nearly all of the superconducting H-T plane
show good temperature scaling of the flux pinning force, suggestive of a
current density determined by flux pinning. At least two length scales are
suggested by the magnetization and magneto optical (MO) analysis but the cause
of this seems to be phase inhomogeneity, porosity, and minority insulating
phase such as MgO rather than by weakly coupled grain boundaries. Our results
suggest that polycrystalline ceramics of this new class of superconductor will
not be compromised by the weak link problems of the high temperature
superconductors, a conclusion with enormous significance for applications if
higher temperature analogs of this compound can be discovered
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