74 research outputs found
On the algorithmic construction of classifying spaces and the isomorphism problem for biautomatic groups
We show that the isomorphism problem is solvable in the class of central
extensions of word-hyperbolic groups, and that the isomorphism problem for
biautomatic groups reduces to that for biautomatic groups with finite centre.
We describe an algorithm that, given an arbitrary finite presentation of an
automatic group , will construct explicit finite models for the skeleta
of and hence compute the integral homology and cohomology of
.Comment: 21 pages, 4 figure
OPENMENDEL: A Cooperative Programming Project for Statistical Genetics
Statistical methods for genomewide association studies (GWAS) continue to
improve. However, the increasing volume and variety of genetic and genomic data
make computational speed and ease of data manipulation mandatory in future
software. In our view, a collaborative effort of statistical geneticists is
required to develop open source software targeted to genetic epidemiology. Our
attempt to meet this need is called the OPENMENDELproject
(https://openmendel.github.io). It aims to (1) enable interactive and
reproducible analyses with informative intermediate results, (2) scale to big
data analytics, (3) embrace parallel and distributed computing, (4) adapt to
rapid hardware evolution, (5) allow cloud computing, (6) allow integration of
varied genetic data types, and (7) foster easy communication between
clinicians, geneticists, statisticians, and computer scientists. This article
reviews and makes recommendations to the genetic epidemiology community in the
context of the OPENMENDEL project.Comment: 16 pages, 2 figures, 2 table
A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses
<p>Abstract</p> <p>Background</p> <p>Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important.</p> <p>Results</p> <p>A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of <it>n </it>= 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (<it>MSTN</it>) [<it>P</it><sub>unadj. </sub>= 6.96 × 10<sup>-6</sup>]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (<it>P</it><sub>unadj. </sub>= 1.61 × 10<sup>-9</sup>; <it>P</it><sub>Bonf. </sub>= 6.58 × 10<sup>-5</sup>). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in <it>MSTN </it>associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the <it>MSTN </it>gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (<it>r</it><sup>2 </sup>= 0.86).</p> <p>Conclusions</p> <p>Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, <it>P </it>= 1.02 × 10<sup>-10</sup>; BIEC2-417495, <it>P</it><sub>unadj. </sub>= 1.61 × 10<sup>-9</sup>). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.</p
Assessment of HIF-1α expression and release following endothelial injury in-vitro and in-vivo
Background: Endothelial injury is an early and enduring feature of cardiovascular disease. Inflammation and hypoxia may be responsible for this, and are often associated with the up-regulation of several transcriptional factors that include Hypoxia Inducible Factor-1 (HIF-1). Although it has been reported that HIF-1α is detectable in plasma, it is known to be unstable. Our aim was to optimize an assay for HIF-1α to be applied to in vitro and in vivo applications, and to use this assay to assess the release kinetics of HIF-1 following endothelial injury.
Methods: An ELISA for the measurement of HIF in cell-culture medium and plasma was optimized, and the assay used to determine the best conditions for sample collection and storage. The results of the ELISA were validated using Western blotting and immunohistochemistry (IHC). In vitro, a standardized injury was produced in a monolayer of rat aortic endothelial cells (RAECs) and intracellular HIF-1α was measured at intervals over 24 hours. In vivo, a rat angioplasty model was used. The right carotid artery was injured using a 2F Fogarty balloon catheter. HIF-1α was measured in the plasma and in the arterial tissue (0, 1, 2, 3 and 5 days post injury).
Results: The HIF-1α ELISA had a limit of detection of 2.7 pg/ mL and was linear up to 1000 pg/ mL. Between and within-assay coefficient of variation values were less than 15%. HIF-1α was unstable in cell lysates and plasma, and it was necessary to add a protease inhibitor immediately after collection, and to store samples at -800C prior to analysis. The dynamics of HIF-1α release were different for the in vitro and in vivo models. In vitro, HIF-1α reached maximum concentrations approximately 2h post injury, whereas peak values in plasma and tissues occurred approximately 2 days post injury, in the balloon injury model.
Conclusion: HIF-1α can be measured in plasma, but this requires careful sample collection and storage. The carotid artery balloon injury model is associated with the transient release of HIF-1α into the circulation that probably reflects the hypoxia induced in the artery wall
Biodiversity of the Deep-Sea Continental Margin Bordering the Gulf of Maine (NW Atlantic): Relationships among Sub-Regions and to Shelf Systems
Background: In contrast to the well-studied continental shelf region of the Gulf of Maine, fundamental questions regarding
the diversity, distribution, and abundance of species living in deep-sea habitats along the adjacent continental margin
remain unanswered. Lack of such knowledge precludes a greater understanding of the Gulf of Maine ecosystem and limits
development of alternatives for conservation and management.
Methodology/Principal Findings: We use data from the published literature, unpublished studies, museum records and
online sources, to: (1) assess the current state of knowledge of species diversity in the deep-sea habitats adjacent to the Gulf
of Maine (39–43uN, 63–71uW, 150–3000 m depth); (2) compare patterns of taxonomic diversity and distribution of
megafaunal and macrofaunal species among six distinct sub-regions and to the continental shelf; and (3) estimate the
amount of unknown diversity in the region. Known diversity for the deep-sea region is 1,671 species; most are narrowly
distributed and known to occur within only one sub-region. The number of species varies by sub-region and is directly
related to sampling effort occurring within each. Fishes, corals, decapod crustaceans, molluscs, and echinoderms are
relatively well known, while most other taxonomic groups are poorly known. Taxonomic diversity decreases with increasing
distance from the continental shelf and with changes in benthic topography. Low similarity in faunal composition suggests
the deep-sea region harbours faunal communities distinct from those of the continental shelf. Non-parametric estimators of
species richness suggest a minimum of 50% of the deep-sea species inventory remains to be discovered.
Conclusions/Significance: The current state of knowledge of biodiversity in this deep-sea region is rudimentary. Our ability
to answer questions is hampered by a lack of sufficient data for many taxonomic groups, which is constrained by sampling
biases, life-history characteristics of target species, and the lack of trained taxonomists
Planck 2015 results. XIII. Cosmological parameters
We present results based on full-mission Planck observations of temperature and polarization anisotropies of the CMB. These data are consistent with the six-parameter inflationary LCDM cosmology. From the Planck temperature and lensing data, for this cosmology we find a Hubble constant, H0= (67.8 +/- 0.9) km/s/Mpc, a matter density parameter Omega_m = 0.308 +/- 0.012 and a scalar spectral index with n_s = 0.968 +/- 0.006. (We quote 68% errors on measured parameters and 95% limits on other parameters.) Combined with Planck temperature and lensing data, Planck LFI polarization measurements lead to a reionization optical depth of tau = 0.066 +/- 0.016. Combining Planck with other astrophysical data we find N_ eff = 3.15 +/- 0.23 for the effective number of relativistic degrees of freedom and the sum of neutrino masses is constrained to < 0.23 eV. Spatial curvature is found to be |Omega_K| < 0.005. For LCDM we find a limit on the tensor-to-scalar ratio of r <0.11 consistent with the B-mode constraints from an analysis of BICEP2, Keck Array, and Planck (BKP) data. Adding the BKP data leads to a tighter constraint of r < 0.09. We find no evidence for isocurvature perturbations or cosmic defects. The equation of state of dark energy is constrained to w = -1.006 +/- 0.045. Standard big bang nucleosynthesis predictions for the Planck LCDM cosmology are in excellent agreement with observations. We investigate annihilating dark matter and deviations from standard recombination, finding no evidence for new physics. The Planck results for base LCDM are in agreement with BAO data and with the JLA SNe sample. However the amplitude of the fluctuations is found to be higher than inferred from rich cluster counts and weak gravitational lensing. Apart from these tensions, the base LCDM cosmology provides an excellent description of the Planck CMB observations and many other astrophysical data sets
Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task
Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia
The Effectiveness of Incarceration-Based Drug Treatment on Criminal Behavior: A Systematic Review
Many, if not most, incarcerated offenders have substance abuse problems. Without effective treatment, these substance-abusing offenders are likely to persist in non-drug offending. The period of incarceration offers an opportunity to intervene in the cycle of drug abuse and crime. Although many types of incarceration-based drug treatment programs are available (e.g., therapeutic communities and group counseling), the effectiveness of these programs is unclear. The objective of this research synthesis is to systematically review quasi-experimental and experimental (RCT) evaluations of the effectiveness of incarceration-based drug treatment programs in reducing post-release recidivism and drug relapse. A secondary objective of this synthesis is to examine variation in effectiveness by programmatic, sample, and methodological features. In this update of the original 2006 review (see Mitchell, Wilson, and MacKenzie, 2006), studies made available since the original review were included in an effort to keep current with emerging research. This synthesis of evaluations of incarceration-based drug treatment programs found that such programs are modestly effective in reducing recidivism. These findings most strongly support the effectiveness of therapeutic communities, as these programs produced relatively consistent reductions in recidivism and drug use. Both counseling and incarceration-based narcotic maintenance programs had mixed effects. Counseling programs were associated with reductions in recidivism but not drug use; whereas, incarceration-based narcotic maintenance programs were associated with reductions in drug use but not recidivism. Note that our findings regarding the effectiveness of incarceration-based narcotic maintenance programs differ from a larger review of community-based narcotic maintenance programs (see Egli, Pina, Christensen, Aebi, and Killias, 2009). Finally, boot camp programs for drug offenders had negligible effects on both recidivism and drug use
Bivalve Characterization Using Synchrotron Micro X-Ray Fluorescence
Bivalves, oysters, mussels, and clams are important constituents of riverine and estuarine ecosystems. Their shells and soft tissues provide information on the environments in which they live. Since they are filter feeders, they also are factors in improving water quality through removal of particulate matter from the water column. Finally, they are a valuable food source that has substantial economic value. Hence, characterization of shells and soft tissues is useful for improved understanding of these factors. Here, we used X-ray microprobes and computed microtomography facilities at the Brookhaven National Synchrotron Light Source to investigate elemental distributions in bivalves taken from locations around New York, Washington, DC, and New Orleans, LA. The results form the initial basis for compilation of a database of relevant parameters that can serve for tracking environmental changes and for assessing toxicity of particular metals. The work was enabled by active collaboration with students from the several regions, community groups, and research scientists. The collaboration was facilitated through use of web conferencing between Brookhaven National Laboratory and the varied locations
Bivalve Characterization Using Synchrotron Micro X-Ray Fluorescence
Bivalves, oysters, mussels, and clams are important constituents of riverine and estuarine ecosystems. Their shells and soft tissues provide information on the environments in which they live. Since they are filter feeders, they also are factors in improving water quality through removal of particulate matter from the water column. Finally, they are a valuable food source that has substantial economic value. Hence, characterization of shells and soft tissues is useful for improved understanding of these factors. Here, we used X-ray microprobes and computed microtomography facilities at the Brookhaven National Synchrotron Light Source to investigate elemental distributions in bivalves taken from locations around New York, Washington, DC, and New Orleans, LA. The results form the initial basis for compilation of a database of relevant parameters that can serve for tracking environmental changes and for assessing toxicity of particular metals. The work was enabled by active collaboration with students from the several regions, community groups, and research scientists. The collaboration was facilitated through use of web conferencing between Brookhaven National Laboratory and the varied locations
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