445 research outputs found

    Modeling large scale species abundance with latent spatial processes

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    Modeling species abundance patterns using local environmental features is an important, current problem in ecology. The Cape Floristic Region (CFR) in South Africa is a global hot spot of diversity and endemism, and provides a rich class of species abundance data for such modeling. Here, we propose a multi-stage Bayesian hierarchical model for explaining species abundance over this region. Our model is specified at areal level, where the CFR is divided into roughly 37,00037{,}000 one minute grid cells; species abundance is observed at some locations within some cells. The abundance values are ordinally categorized. Environmental and soil-type factors, likely to influence the abundance pattern, are included in the model. We formulate the empirical abundance pattern as a degraded version of the potential pattern, with the degradation effect accomplished in two stages. First, we adjust for land use transformation and then we adjust for measurement error, hence misclassification error, to yield the observed abundance classifications. An important point in this analysis is that only 2828% of the grid cells have been sampled and that, for sampled grid cells, the number of sampled locations ranges from one to more than one hundred. Still, we are able to develop potential and transformed abundance surfaces over the entire region. In the hierarchical framework, categorical abundance classifications are induced by continuous latent surfaces. The degradation model above is built on the latent scale. On this scale, an areal level spatial regression model was used for modeling the dependence of species abundance on the environmental factors.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS335 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli

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    Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as “phenotypic noise.” In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for over 60% of all promoters in Escherichia coli. We find that essential genes and genes with a high degree of evolutionary conservation have promoters that confer low levels of noise. We also find that the level of noise cannot be attributed to the evolutionary time that different genes have spent in the genome of E. coli. In contrast to previous results in eukaryotes, we find no association between promoter-mediated noise and gene expression plasticity. These results are consistent with the hypothesis that, in bacteria, natural selection can act to reduce gene expression noise and that some of this noise is controlled through the sequence of the promoter region alon

    Echium oil is not protective against weight loss in head and neck cancer patients undergoing curative radio(chemo)therapy: a randomised-controlled trial

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    Background: Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. Methods: In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected. Results: Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs −5%) and n-6 GLA (42% vs −20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs −1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters. Conclusions: Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters. Trial registration: ClinicalTrials.gov Identifier NCT01596933

    Large Scale Association Analysis of Novel Genetic Loci for Coronary Artery Disease

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    Background-Combined analysis of 2 genome-wide association studies in cases enriched for family history recently identified 7 loci (on 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21, 10q11.21, and 15q22.33) that may affect risk of coronary artery disease (CAD). Apart from the 9p21 locus, the other loci await substantive replication. Furthermore, the effect of these loci on CAD risk in a broader range of individuals remains to be determined.Methods and Results-We undertook association analysis of single nucleotide polymorphisms at each locus with CAD risk in 11 550 cases and 11 205 controls from 9 European studies. The 9p21.3 locus showed unequivocal association (rs1333049, combined odds ratio [OR]=1.20, 95% CI [1.16 to 1.25], probability value=2.81x10(-21)). We also confirmed association signals at 1p13.3 (rs599839, OR=1.13 [1.08 to 1.19], P=1.44x10(-7)), 1q41 (rs3008621, OR=1.10 [1.04 to 1.17], P=1.02x10(-3)), and 10q11.21 (rs501120, OR=1.11 [1.05 to 1.18], P=4.34x10(-4)). The associations with 6q25.1 (rs6922269, P=0.020) and 2q36.3 (rs2943634, P=0.032) were borderline and not statistically significant after correction for multiple testing. The 15q22.33 locus did not replicate. The 10q11.21 locus showed a possible sex interaction (P = 0.015), with a significant effect in women (OR=1.29 [1.15 to 1.45], P=1.86x10(-5)) but not men (OR=1.03 [0.96 to 1.11], P=0.387). There were no other strong interactions of any of the loci with other traditional risk factors. The loci at 9p21, 1p13.3, 2q36.3, and 10q11.21 acted independently and cumulatively increased CAD risk by 15% (12% to 18%), per additional risk allele. ConclusionsThe findings provide strong evidence for association between at least 4 genetic loci and CAD risk. Cumulatively, these novel loci have a significant impact on risk of CAD at least in European populations. (Arterioscler Thromb Vasc Biol. 2009; 29: 774-780.

    Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment.

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    Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltrates yet have opposing prognoses. The microbiome has previously been associated with CRC and immune response in CRC but has largely been ignored in the CRC subtype discussion. We used CMS subtyping on surgical resections from patients and aimed to determine the contributions of the microbiome to the pleiotropic effects evident in immune-infiltrated subtypes. We integrated host gene-expression and meta-transcriptomic data to determine the link between immune characteristics and microbiome contributions in these subtypes and identified lipopolysaccharide (LPS) binding as a potential functional mechanism. We identified candidate bacteria with LPS properties that could affect immune response, and tested the effects of their LPS on cytokine production of peripheral blood mononuclear cells (PBMCs). We focused on Fusobacterium periodonticum and Bacteroides fragilis in CMS1, and Porphyromonas asaccharolytica in CMS4. Treatment of PBMCs with LPS isolated from these bacteria showed that F. periodonticum stimulates cytokine production in PBMCs while both B. fragilis and P. asaccharolytica had an inhibitory effect. Furthermore, LPS from the latter two species can inhibit the immunogenic properties of F. periodonticum LPS when co-incubated with PBMCs. We propose that different microbes in the CRC tumor microenvironment can alter the local immune activity, with important implications for prognosis and treatment response.fals

    CIRCULAR COMPARISON OF CONVENTIONAL PRESSURE STANDARDS USING A TRANSPORTABLE OPTICAL REFRACTOMETER: PREPARATION AND TRANSPORTATION

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    Using a transportable Fabry-Pérot cavity refractometer, a circular comparison of existing primary standards at several national metrology institutes is currently underway. This paper provides information about the refractometer, the preparation for the comparison, and the transportation procedur

    Update of the Minimum Information About BIobank Data Sharing (MIABIS) Core Terminology to the 3<sup>rd</sup> Version

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    Introduction: The Minimum Information About BIobank Data Sharing (MIABIS) is a biobank-specific terminology enabling the sharing of biobank-related data for different purposes across a wide range of database implementations. After 4 years in use and with the first version of the individual-level MIABIS component Sample, Sample donor, and Event, it was necessary to revise the terminology, especially to include biobanks that work more in the data domain than with samples.Materials &amp; Methods: Nine use-cases representing different types of biobanks, studies, and networks participated in the development work. They represent types of data, specific sample types, or levels of organization that were not included earlier in MIABIS. To support our revision of the Biobank entity, we conducted a survey of European biobanks to chart the services they provide. An important stakeholder group for biobanks include researchers as the main users of biobanks. To be able to render MIABIS more researcher-friendly, we collected different sample/data requests to analyze the terminology adjustment needs in detail. During the update process, the Core terminology was iteratively reviewed by a large group of experts until a consensus was reached.Results: With this update, MIABIS was adjusted to encompass data-driven biobanks and to include data collections, while also describing the services and capabilities biobanks offer to their users, besides the retrospective samples. The terminology was also extended to accommodate sample and data collections of nonhuman origin. Additionally, a set of organizational attributes was compiled to describe networks.Discussion: The usability of MIABIS Core v3 was increased by extending it to cover more topics of the biobanking domain. Additionally, the focus was on a more general terminology and harmonization of attributes with the individual-level entities Sample, Sample donor, and Event to keep the overall terminology minimal. With this work, the internal semantics of the MIABIS terminology was improved

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Explaining species distribution patterns through hierarchical modeling

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    Understanding spatial patterns of species diversity and the distri- butions of individual species is a consuming problem in biogeography and con- servation. The Cape Floristic Region (CFR) of South Africa is a global hotspot of diversity and endemism, and the Protea Atlas Project, with some 60,000 site records across the region, provides an extraordinarily rich data set to analyze bio- diversity patterns. Analysis for the region is developed at the spatial scale of one minute grid-cells ( 37; 000 cells total for the region). We report on results for 40 species of a owering plant family Proteaceae (of about 330 in the CFR) for a de ned subregion. Using a Bayesian framework, we develop a two stage, spatially explicit, hierar- chical logistic regression. Stage one models the suitability or potential presence for each species at each cell, given species attributes along with grid cell (site-level) climate, precipitation, topography and geology data using species-level coe cients, and a spatial random e ect. The second level of the hierarchy models, for each species, observed presence=absence at a sampling site through a conditional speci- cation of the probability of presence at an arbitrary location in the grid cell given that the location is suitable. Because the atlas data are not evenly distributed across the landscape, grid cells contain variable numbers of sampling localities. Indeed, some grid cells are entirely unsampled; others have been transformed by human intervention (agriculture, urbanization) such that none of the species are there though some may have the potential to be present in the absence of distur- bance. Thus the modeling takes the sampling intensity at each site into account by assuming that the total number of times that a particular species was observed within a site follows a binomial distribution.In fact, a range of models can be examined incorporating di erent rst and second stage speci cations. This necessitates model comparison in a misaligned multilevel setting. All models are tted using MCMC methods. A best" model is selected. Parameter summaries o er considerable insight. In addition, results are mapped as the model-estimated potential presence for each species across the domain. This probability surface provides an alternative to customary empiri- cal \range of occupancy" displays. Summing yields the predicted species richness over the region. Summaries of the posterior for each environmental coe cient show which variables are most important in explaining species presence. Other biodi- versity measures emerge as model unknowns. A considerable range of inference is available. We illustrate with only a portion of the analyses we have conducted, noting that these initial results describe biogeographical patterns over the modeled region remarkably well

    Quantum-based realizations of the pascal: status and progress of the EMPIR-project: quantumpascal

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    The QuantumPascal (QP) project combines the capabilities of 12 European institutions to enable traceable pressure measurements utilizing quantum-based methods that evaluate the number density instead of force per area to target the wide pressure range between 1 Pa and 3 MPa. This article summarizes the goals and results since the project start in June 201
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