Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on horse chromosome 6

<p>Abstract</p> <p>Background</p> <p>Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain horse breed where it occurs at a high frequency among Silver colored horses. The Silver coat color is associated with mutations in <it>PMEL17 </it>that resides on ECA6q23. To map the <it>MCOA </it>locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the <it>MCOA </it>locus.</p> <p>Results</p> <p>We performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in <it>PMEL17</it>. Significant linkage was found between the <it>MCOA </it>locus and eight of the genetic markers, where marker <it>UPP5 </it>(Theta = 0, z = 12.3), <it>PMEL17ex11 </it>(Theta = 0, z = 19.0) and <it>UPP6 </it>(Theta = 0, z = 17.5) showed complete linkage with the <it>MCOA </it>locus. DNA sequencing of <it>PMEL17 </it>in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color.</p> <p>Conclusion</p> <p>The <it>MCOA </it>locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on <it>UPP5</it>, <it>PMEL17ex11 </it>and <it>UPP6 </it>strongly support the hypothesis that horses with the Cyst phenotype are heterozygous for the mutant allele and that horses with the MCOA phenotype are homozygous for the mutant allele.</p

Polynomial-time algorithm for simulation of weakly interacting quantum spin systems

We describe an algorithm that computes the ground state energy and correlation functions for 2-local Hamiltonians in which interactions between qubits are weak compared to single-qubit terms. The running time of the algorithm is polynomial in the number of qubits and the required precision. Specifically, we consider Hamiltonians of the form $H=H_0+\epsilon V$, where H_0 describes non-interacting qubits, V is a perturbation that involves arbitrary two-qubit interactions on a graph of bounded degree, and $\epsilon$ is a small parameter. The algorithm works if $|\epsilon|$ is below a certain threshold value that depends only upon the spectral gap of H_0, the maximal degree of the graph, and the maximal norm of the two-qubit interactions. The main technical ingredient of the algorithm is a generalized Kirkwood-Thomas ansatz for the ground state. The parameters of the ansatz are computed using perturbative expansions in powers of $\epsilon$. Our algorithm is closely related to the coupled cluster method used in quantum chemistry.Comment: 27 page

Point process models for spatio-temporal distance sampling data from a large-scale survey of blue whales

Distance sampling is a widely used method for estimating wildlife population abundance. The fact that conventional distance sampling methods are partly design-based constrains the spatial resolution at which animal density can be estimated using these methods. Estimates are usually obtained at survey stratum level. For an endangered species such as the blue whale, it is desirable to estimate density and abundance at a finer spatial scale than stratum. Temporal variation in the spatial structure is also important. We formulate the process generating distance sampling data as a thinned spatial point process and propose model-based inference using a spatial log-Gaussian Cox process. The method adopts a flexible stochastic partial differential equation (SPDE) approach to model spatial structure in density that is not accounted for by explanatory variables, and integrated nested Laplace approximation (INLA) for Bayesian inference. It allows simultaneous fitting of detection and density models and permits prediction of density at an arbitrarily fine scale. We estimate blue whale density in the Eastern Tropical Pacific Ocean from thirteen shipboard surveys conducted over 22 years. We find that higher blue whale density is associated with colder sea surface temperatures in space, and although there is some positive association between density and mean annual temperature, our estimates are consitent with no trend in density across years. Our analysis also indicates that there is substantial spatially structured variation in density that is not explained by available covariates.Comment: 33 pages 19 figure

A Bayesian General Linear Modeling Approach to Cortical Surface fMRI Data Analysis

Cortical surface functional magnetic resonance imaging (cs-fMRI) has recently grown in popularity versus traditional volumetric fMRI. In addition to offering better whole-brain visualization, dimension reduction, removal of extraneous tissue types, and improved alignment of cortical areas across subjects, it is also more compatible with common assumptions of Bayesian spatial models. However, as no spatial Bayesian model has been proposed for cs-fMRI data, most analyses continue to employ the classical general linear model (GLM), a “massive univariate” approach. Here, we propose a spatial Bayesian GLM for cs-fMRI, which employs a class of sophisticated spatial processes to model latent activation fields. We make several advances compared with existing spatial Bayesian models for volumetric fMRI. First, we use integrated nested Laplacian approximations, a highly accurate and efficient Bayesian computation technique, rather than variational Bayes. To identify regions of activation, we utilize an excursions set method based on the joint posterior distribution of the latent fields, rather than the marginal distribution at each location. Finally, we propose the first multi-subject spatial Bayesian modeling approach, which addresses a major gap in the existing literature. The methods are very computationally advantageous and are validated through simulation studies and two task fMRI studies from the Human Connectome Project. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement

Search for Fractional Charges in Water

Results are presented from a search for fractional charges in water from a variety of natural sources. About 30 000 water drops have been measured, comprising 51 μg of water and dissolved materials. No evidence for fractional charge was seen

Structural Information in Two-Dimensional Patterns: Entropy Convergence and Excess Entropy

We develop information-theoretic measures of spatial structure and pattern in more than one dimension. As is well known, the entropy density of a two-dimensional configuration can be efficiently and accurately estimated via a converging sequence of conditional entropies. We show that the manner in which these conditional entropies converge to their asymptotic value serves as a measure of global correlation and structure for spatial systems in any dimension. We compare and contrast entropy-convergence with mutual-information and structure-factor techniques for quantifying and detecting spatial structure.Comment: 11 pages, 5 figures, http://www.santafe.edu/projects/CompMech/papers/2dnnn.htm

Magnetism and transport in transparent high-mobility BaSnO3 films doped with La, Pr, Nd, and Gd

We have explored the effect of magnetic rare-earth dopants substitutionally incorporated on the Ba sites of BaSnO3 in terms of electronic transport, magnetism, and optical properties. We show that for Ba0.92R0.08SnO3 thin films (where R=La,Pr,Nd,Gd), there is a linear increase of mobility with carrier concentration across all doping schemes. La-doped films have the highest mobilities, followed by Pr- and Nd-doped films. Gd-doped samples have the largest ionic size mismatch with the Ba site and correspondingly the lowest carrier concentrations and electron mobilities. However, crystallinity does not appear to be a strong predictor of transport phenomena; our results suggest that point defects more than grain boundaries are key ingredients in tuning the conduction of BaSnO3 films grown by pulsed laser deposition. Pronounced, nonhysteretic x-ray magnetic dichroism signals are observed for Pr-, Nd-, and Gd-doped samples, indicating paramagnetism. Finally, we probe the optical constants for each of the BaSnO3 doping schemes and note that there is little change in the transmittance across all samples. Together these results shed light on conduction mechanisms in BaSnO3 doped with rare-earth cations

Interparticle interactions:Energy potentials, energy transfer, and nanoscale mechanical motion in response to optical radiation

In the interactions between particles of material with slightly different electronic levels, unusually large shifts in the pair potential can result from photoexcitation, and on subsequent electronic excitation transfer. To elicit these phenomena, it is necessary to understand the fundamental differences between a variety of optical properties deriving from dispersion interactions, and processes such as resonance energy transfer that occur under laser irradiance. This helps dispel some confusion in the recent literature. By developing and interpreting the theory at a deeper level, one can anticipate that in suitable systems, light absorption and energy transfer will be accompanied by significant displacements in interparticle separation, leading to nanoscale mechanical motion

Search for Fractional Charges Produced in Heavy-Ion Collisions at 1.9 GeV/nucleon

An experiment was performed to capture fractionally charged particles produced in heavy-ion collisions and to concentrate them in samples suitable for analysis by various techniques. Two of the samples so produced have been searched, with use of an automated version of Millikan\u27s oil-drop apparatus. The beam was 56Fe at 1.9 GeV/nucleon, incident on a lead target. Less than one fractional charge per 1.0× 104 Fe-Pb collisions was found to be produced, and, with further assumptions, less than one per 2.0× 106 collisions

Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85610 x 10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84 x 10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at similar to 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults