Two-Locus Likelihoods under Variable Population Size and Fine-Scale Recombination Rate Estimation

Two-locus sampling probabilities have played a central role in devising an efficient composite likelihood method for estimating fine-scale recombination rates. Due to mathematical and computational challenges, these sampling probabilities are typically computed under the unrealistic assumption of a constant population size, and simulation studies have shown that resulting recombination rate estimates can be severely biased in certain cases of historical population size changes. To alleviate this problem, we develop here new methods to compute the sampling probability for variable population size functions that are piecewise constant. Our main theoretical result, implemented in a new software package called LDpop, is a novel formula for the sampling probability that can be evaluated by numerically exponentiating a large but sparse matrix. This formula can handle moderate sample sizes ($n \leq 50$) and demographic size histories with a large number of epochs ($\mathcal{D} \geq 64$). In addition, LDpop implements an approximate formula for the sampling probability that is reasonably accurate and scales to hundreds in sample size ($n \geq 256$). Finally, LDpop includes an importance sampler for the posterior distribution of two-locus genealogies, based on a new result for the optimal proposal distribution in the variable-size setting. Using our methods, we study how a sharp population bottleneck followed by rapid growth affects the correlation between partially linked sites. Then, through an extensive simulation study, we show that accounting for population size changes under such a demographic model leads to substantial improvements in fine-scale recombination rate estimation. LDpop is freely available for download at https://github.com/popgenmethods/ldpopComment: 32 pages, 13 figure

Standardized Waterproof Testing of Plastic Based Material Flooring (PBM Flooring)

Tile Council of North America Product Performance Testing Laboratory, under the direction of Dr. John Sanders of the Bishop Materials Laboratory at Clemson University, evaluated the extent that water can leak through plastic based material (PBM)1 floor coverings advertised as 100% waterproof. To make this assessment, product literature was examined to determine which test methods were used to support the manufacturers’2 claims of products being waterproof. Neither test methods or data to justify a 100% waterproof claim were found, despite a thorough review of product literature.3 ASTM, ANSI, ISO, and CEN standards were examined for relevant test methods for waterproofness. Two methods were identified: (1) EN 13553, Resilient Floor Coverings - Polyvinyl Chloride Floor Coverings for Use in Special Wet Areas – Specification, is used to assess water penetration for plastic flooring materials, and (2) ASTM D4068, Standard Specification for Chlorinated Polyethylene Sheeting for Concealed Water-Containment Membrane, is used to assess waterproof membranes commonly used in wet area applications to protect the substrate. To be considered watertight, both methods specify that test specimens show no evidence of water leaking during testing. All the products tested for this report failed to meet the criteria outlined in EN 13553 and ASTM D4068. Testing results for each product are detailed in section 6.2 for EN 13553, and section 6.3 for ASTM D4068. When the results from EN 13553 are extrapolated to the area of an average bathroom (40 square feet)4, flow rates ranged from 12.1 L/hr. (3.2 Gal/hr.) to 187.0 L/hr. (49.4 Gal/hr.). As detailed in section 3, these volumes of water can do significant damage to a home. This report shows that the PBM products tested leak under the conditions of the test methods. Believing the products are waterproof as advertised could lead to an inappropriate flooring selection and may result in damage to the subfloor and surrounding areas. The results from this report suggest a dry use-only caution, or warning regarding lack of waterproofness, should be considered for products that perform similarly to those tested in this repor

Relativistic Meson Spectroscopy and In-Medium Effects

We extend our earlier model of $q\bar q$ mesons using relativistic quasipotential (QP) wave equations to include open-flavor states and running quark-gluon coupling effects. Global fits to meson spectra are achieved with rms deviations from experiment of 43-50 MeV. We examine in-medium effects through their influence on the confining interaction and predict the confining strength at which the masses of certain mesons fall below the threshold of their dominant decay channel.Comment: 12 Pages, 2 Postscript figures (appended at the end with instructions, available also from [email protected]

Three-Tone Coherent Microwave Electromechanical Measurement of a Superfluid Helmholtz Resonator

We demonstrate electromechanical coupling between a superfluid mechanical mode and a microwave mode formed by a patterned microfluidic chip and a 3D cavity. The electric field of the chip-cavity microwave resonator can be used to both drive and detect the motion of a pure superflow Helmholtz mode, which is dictated by geometric confinement. The coupling is characterized using a coherent measurement technique developed for measuring weak couplings deep in the sideband unresolved regime. The technique is based on two-probe optomechanically induced transparency/amplification using amplitude modulation. Instead of measuring two probe tones separately, they are interfered to retain only a signal coherent with the mechanical motion. With this method, we measure a vacuum electromechanical coupling strength of $g_0 = 2\pi \times 23.3$ $\mathrm{\mu}$Hz, three orders of magnitude larger than previous superfluid electromechanical experiments.Comment: 13 pages, 6 figures, submitted to Appl. Phys. Lett., out for peer review, revte

Revised Keys and Additions to the Australian Bryaceae (Bryopsida)

Revised keys to the Bryaceae flora of Australia and its offshore islands are presented, including new keys to genera and to species within each genus. Sixty named species and two undetermined taxa are included in the treatments. Leptostomopsis pulchra (Hook.) Ochyra & Bedn.-Ochyra is reported from near Melbourne, Victoria as a new genus and species to Australia. Notes on each species are included, and comparisons made with the closely similar Bryaceae of New Zealand

Expression profiling and QTL analysis: a powerful complementary strategy in drug abuse research

Alcoholism is a complex disease exhibiting a multifactorial mode of transmission. To simplify the genetic and phenotypic complexity of the alcoholic phenotype, alcohol-preferring (P) and -non-preferring (NP) rats were developed on the basis of alcohol preference and consumption as an animal model of alcoholism. Total gene expression analysis (TOGA) and quantitative trait loci (QTL) analysis were applied to selectively bred, inbred P and NP rats as complementary studies to identify genetic factors that contribute to alcohol preference and consumption. TOGA analysis was utilized to screen for differential expression in several brain regions involved in the mesocorticolimbic dopamine (DA) system. Genes exhibiting differences in expression were then screened for an association to the alcohol preference phenotype, the quantitative trait of a previously identified QTL. By evaluating differences in gene expression for linkage to a quantitative trait, this combined approach was implemented to identify alpha-synuclein, a candidate gene for alcohol preference

Ultradeep analysis of tumor heterogeneity in regions of somatic hypermutation

Abstract Tumor heterogeneity is of growing importance in the treatment of cancers. Mutational hot spots are prime locations for determining number and proportions of low variant allele frequency (VAF) tumor subclones by next generation sequencing. Low VAF detection is complicated by poor mapping efficiency in regions with high mutation density. Our Deep-Drilling with iterative Mapping (DDiMAP) method retains variant allele patterns to aid in single nucleotide variation detection and generation of additional reference alleles, with remapping increasing coverage of highly mutated regions to capture data critical to heterogeneity analysis and enhancing sensitivity. DDiMAP outputs variant patterns with frequencies, enabling rapid phylogenetic analysis of ongoing mutation

High-resolution ab initio three-dimensional X-ray diffraction microscopy

Coherent X-ray diffraction microscopy is a method of imaging non-periodic isolated objects at resolutions only limited, in principle, by the largest scattering angles recorded. We demonstrate X-ray diffraction imaging with high resolution in all three dimensions, as determined by a quantitative analysis of the reconstructed volume images. These images are retrieved from the 3D diffraction data using no a priori knowledge about the shape or composition of the object, which has never before been demonstrated on a non-periodic object. We also construct 2D images of thick objects with infinite depth of focus (without loss of transverse spatial resolution). These methods can be used to image biological and materials science samples at high resolution using X-ray undulator radiation, and establishes the techniques to be used in atomic-resolution ultrafast imaging at X-ray free-electron laser sources.Comment: 22 pages, 11 figures, submitte

From QTL to candidate gene: a genetic approach to alcoholism research

A major focus of research in alcohol-related disorders is to identify the genes and pathways that modulate alcohol-seeking behavior. In light of this, animal models have been established to study various aspects of alcohol dependence. The selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines were developed from Wistar rats to model high and low voluntary alcohol consumption, respectively. Using inbred P and NP strains, a strong QTL (LOD-9.2) for alcohol consumption was identified on rat chromosome 4. To search for candidate genes that underlie this chromosomal region, complementary molecular-based strategies were implemented to identify genetic targets that likely contribute to the linkage signal. In an attempt to validate these genetic targets, corroborative studies have been utilized including pharmacological studies, knock-out/transgenic models as well as human association studies. Thus far, three candidate genes, neuropeptide Y (Npy), alpha-synuclein (Snca), and corticotrophin-releasing factor receptor 2 (Crhr2), have been identified that may account for the linkage signal. With the recent advancements in bioinformatics and molecular biology, QTL analysis combined with molecular-based strategies provides a systematic approach to identify candidate genes that contribute to various aspects of addictive behavior

A Descriptive Profile of Physical Education Teachers and Related Program Characteristics in Alberta

A survey of teachers and principals in Alberta was conducted to gain a descriptive profile of who is leaching physical education (PE) and to assess the relationship between PE specialists and variables associated with program delivery. A probability-sampling procedure was used to obtain a representative sample of schools. In these schools nonprobability procedures were used to recruit teachers. A total of'480 teachers' and 162 principals' questionnaires were returned. Although 50% (n=236) of PE teachers in the sample were classified as PE specialists (i.e., had either a degree, major or minor, in PE or a closely related area), there was a significant gap in the number of PE classes being taught by division. Of the 1,219 PE classes surveyed in this study, PE specialists taught 49% and 55% of classes at the elementary levels (Divisions I & 11) compared with 91% of junior high (Division III) and 90% of secondary (Division TV) PE classes. Significant differences were found between PE specialists and non-PE specialists on a number of items including perceptions of preparedness, teaching enjoyment and competence to teach PE, the number of PE specialists across grade levels, and the percentage of time devoted to PE in the timetable. Implications with respect to implementing PE specialists across all grades and the need for future pedagogical research to investigate the effect of PE specialists are also discussed.Une enquête a été entreprise auprès d'enseignants et de directeurs d'école en Alberta dans le but d'établir un profil descriptif des enseignants d'éducation physique (EP) et d'évaluer le rapport entre les spécialistes en EP et les variables associées à l'exécution de programmes. On a eu recours aune méthode d'échantillonnage au hasard pour obtenir un échantillon représentatif des écoles. Par la suite, on y a employé des procédures non probabilistes pour recruter des enseignants. En tout, 642 questionnaires (480 provenant d'enseignants et 162 de directeurs) nous ont été renvoyés. Alors que 50% (n=236) des enseignants de EP de l'échantillon se classaient comme spécialistes en EP (c'est-à-dire qu'ils avaient soit un diplôme, une majeure ou une mineure en EP ou dans un domaine connexe), un écart notable existait dans le nombre de cours de EP enseignés par division. Des 1 219 cours de EP inclus dans l'enquête, à l'élémentaire, 49% (Division I) et 55% (Division II) d'entre eux étaient enseignés par des spécialistes en EP. Au secondaire premier cycle (Division III), 91% des cours étaient enseignés par des spécialistes en EP; au secondaire (Division IV), 90% des cours l'étaient. Des différences importantes distinguaient les spécialistes en EP des non spécialistes, y compris leurs perceptions quant à leur état de préparation, le plaisir qu'il retirait de l'enseignement de l'EP, leur compétence à le faire, le nombre de spécialistes en EP à tous les niveaux scolaires et le nombre d'heures consacrées aux cours de EP. Une discussion portant sur les implications de la mise en place de spécialistes en EP à tous les niveaux scolaires et sur la nécessité d'étudier l'effet qu'exercent ceux-ci, termine l'article