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The role of empirical space-weather models (in a world of physics-based numerical simulations)
Advanced forecasting of space weather requires prediction of near-Earth solar-wind conditions on the basis of remote solar observations. This is typically achieved using numerical magnetohydrodynamic models initiated by photospheric magnetic field observations. The accuracy of such forecasts is being continually improved through better numerics, better determination of the boundary conditions and better representation of the underlying physical processes. Thus it is not unreasonable to conclude that simple, empirical solar-wind forecasts have been rendered obsolete. However, empirical models arguably have more to contribute now than ever before. In addition to providing quick, cheap, independent forecasts, simple empirical models aid in numerical model validation and verification, and add value to numerical model forecasts through parameterization, uncertainty estimation and âdownscalingâ of sub-grid processes
Can we find the genes involved in complex traits?
A report on the third Complex Trait Consortium meeting, Bar Harbor, USA, 6-9 July 2004
Comparative analysis of haplotype association mapping algorithms
BACKGROUND: Finding the genetic causes of quantitative traits is a complex and difficult task. Classical methods for mapping quantitative trail loci (QTL) in miceuse an F2 cross between two strains with substantially different phenotype and an interval mapping method to compute confidence intervals at each position in the genome. This process requires significant resources for breeding and genotyping, and the data generated are usually only applicable to one phenotype of interest. Recently, we reported the application of a haplotype association mapping method which utilizes dense genotyping data across a diverse panel of inbred mouse strains and a marker association algorithm that is independent of any specific phenotype. As the availability of genotyping data grows in size and density, analysis of these haplotype association mapping methods should be of increasing value to the statistical genetics community. RESULTS: We describe a detailed comparative analysis of variations on our marker association method. In particular, we describe the use of inferred haplotypes from adjacent SNPs, parametric and nonparametric statistics, and control of multiple testing error. These results show that nonparametric methods are slightly better in the test cases we study, although the choice of test statistic may often be dependent on the specific phenotype and haplotype structure being studied. The use of multi-SNP windows to infer local haplotype structure is critical to the use of a diverse panel of inbred strains for QTL mapping. Finally, because the marginal effect of any single gene in a complex disease is often relatively small, these methods require the use of sensitive methods for controlling family-wise error. We also report our initial application of this method to phenotypes cataloged in the Mouse Phenome Database. CONCLUSION: The use of inbred strains of mice for QTL mapping has many advantages over traditional methods. However, there are also limitations in comparison to the traditional linkage analysis from F2 and RI lines. Application of these methods requires careful consideration of algorithmic choices based on both theoretical and practical factors. Our findings suggest general guidelines, though a complete evaluation of these methods can only be performed as more genetic data in complex diseases becomes available
A structural rationale for N-methylbicuculline acting as a promiscuous competitive antagonist of inhibitory pentameric ligand gated ion channels
Spatio-Temporal Linear Stability Analysis of Stratified Planar Wakes: Velocity and Density Asymmetry Effects
This paper explores the hydrodynamic stability of bluff body wakes with non-uniform mean density, asymmetric mean density, and velocity profiles. This work is motivated by experiments [S. Tuttle et al., âLean blow off behavior of asymmetrically-fueled bluff body-stabilized flames,â Combust. Flame 160, 1677 (2013)], which investigated reacting wakes with equivalence ratio stratification and, hence, asymmetry in the base flow density profiles. They showed that highly stratified cases exhibited strong, narrowband oscillations, suggestive of global hydrodynamic instability. In this paper, we present a local hydrodynamic stability analysis for non-uniform density wakes that includes base flow asymmetry. The results show that increasing the degree of base density asymmetry generally has a destabilizing effect and that increasing base velocity asymmetry tends to be stabilizing. Furthermore, we show that increasing base density asymmetry slightly decreases the absolute frequency and that increasing the base velocity asymmetry slightly increases the absolute frequency. In addition, we show that increasing the degree of base density asymmetry distorts the most absolutely unstable hydrodynamic mode from its nominally sinuous structure. This distorted mode exhibits higher amplitude pressure and velocity oscillations near the interface with the smaller density jump than near the one with the bigger density jump. This would then be anticipated to lead to strongly non-symmetric amplitudes of flame flapping, with much stronger flame flapping on the side with lower density ratio. These predictions are shown to be consistent with experimental data. These comparisons support the analytical predictions that increased base density asymmetry are destabilizing and that hydrodynamic velocity fluctuation amplitudes should be greatest at the flame with the lowest density jump
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