Positive selection on a bacterial oncoprotein associated with gastric cancer

<p>Background</p> <p><it>Helicobacter pylori </it>is a vertically inherited gut commensal that is carcinogenic if it possesses the <it>cag</it> pathogenicity island (<it>cag </it>PaI); infection with <it>H.pylori </it>is the major risk factor for gastric cancer, the second leading cause of death from cancer worldwide (WHO). The <it>cag </it>PaI locus encodes the <it>cagA </it>gene, whose protein product is injected into stomach epithelial cells via a Type IV secretion system, also encoded by the <it>cag </it>PaI. Once there, the cagA protein binds to various cellular proteins, resulting in dysregulation of cell division and carcinogenesis. For this reason, cagA may be described as an oncoprotein. A clear understanding of the mechanism of action of cagA and its benefit to the bacteria is lacking.</p> <p>Results</p> <p>Here, we reveal that the <it>cagA </it>gene displays strong signatures of positive selection in bacteria isolated from amerindian populations, using the Ka/Ks ratio. Weaker signatures are also detected in the gene from bacteria isolated from asian populations, using the Ka/Ks ratio and the more sensitive branches-sites model of the PAML package. When the <it>cagA </it>gene isolated from amerindian populations was examined in more detail it was found that the region under positive selection contains the EPIYA domains, which are known to modulate the carcinogenicity of the gene. This means that the carcinogenicity modulating region of the gene is undergoing adaptation. The results are discussed in relation to the high incidences of stomach cancer in some latin american and asian populations.</p> <p>Conclusion</p> <p>Positive selection on cagA indicates antagonistic coevolution between host and bacteria, which appears paradoxical given that cagA is detrimental to the human host upon which the bacteria depends. This suggests several non-exclusive possibilities; that gastric cancer has not been a major selective pressure on human populations, that cagA has an undetermined benefit to the human host, or that horizontal transmission of <it>H.pylori </it>between hosts has been more important in the evolution of <it>H.pylori </it>than previously recognized, reducing the selective pressure to lower the pathogenicity of the bacteria. The different patterns of adaptation of the gene in different human populations indicates that there are population specific differences in the human gut environment - due either to differences in host genetics or diet and other lifestyle features.</p

Computational Aeroelastic Analysis of the Ares Launch Vehicle During Ascent

This paper presents the static and dynamic computational aeroelastic (CAE) analyses of the Ares crew launch vehicle (CLV) during atmospheric ascent. The influence of launch vehicle flexibility on the static aerodynamic loading and integrated aerodynamic force and moment coefficients is discussed. The ultimate purpose of this analysis is to assess the aeroelastic stability of the launch vehicle along the ascent trajectory. A comparison of analysis results for several versions of the Ares CLV will be made. Flexible static and dynamic analyses based on rigid computational fluid dynamic (CFD) data are compared with a fully coupled aeroelastic time marching CFD analysis of the launch vehicle

On the Origin of Biomolecular Networks

Biomolecular networks have already found great utility in characterizing complex biological systems arising from pairwise interactions amongst biomolecules. Here, we explore the important and hitherto neglected role of information asymmetry in the genesis and evolution of such pairwise biomolecular interactions. Information asymmetry between sender and receiver genes is identified as a key feature distinguishing early biochemical reactions from abiotic chemistry, and a driver of network topology as biomolecular systems become more complex. In this context, we review how graph theoretical approaches can be applied not only for a better understanding of various proximate (mechanistic) relations, but also, ultimate (evolutionary) structures encoded in such networks from among all types of variations they induce. Among many possible variations, we emphasize particularly the essential role of gene duplication in terms of signaling game theory, whereby sender and receiver gene players accrue benefit from gene duplication, leading to a preferential attachment mode of network growth. The study of the resulting dynamics suggests many mathematical/computational problems, the majority of which are intractable yet yield to efficient approximation algorithms, when studied through an algebraic graph theoretic lens. We relegate for future work the role of other possible generalizations, additionally involving horizontal gene transfer, sexual recombination, endo-symbiosis, etc., which enrich the underlying graph theory even further

Active Flutter Suppression Controllers Derived from Linear and Nonlinear Aerodynamics: Application to a Transport Aircraft Model

Active flutter suppression has been demonstrated in simulation by many researchers, generally using methods based on linear aerodynamics and often with simplistic geometries. In this paper, active flutter suppression is demonstrated in a simulation using a Navier-Stokes aerodynamics code, FUN3D (Fully Unstructured Navier-Stokes Three-Dimensional), and a realistic transport aircraft configuration. This is accomplished using simple observer-feedback controllers derived from linear aeroelastic models, including reduced order models built via FUN3D data. The development of these reduced order models is described here. It is shown that controllers derived from reduced order models of the nonlinear aerodynamics outperform controllers based on linear aerodynamics

SmileFinder: A Resampling-Based Approach to Evaluate Signatures of Selection from Genome-Wide Sets of Matching Allele Frequency Data in Two or More Diploid Populations

Background: Adaptive alleles may rise in frequency as a consequence of positive selection, creating a pattern of decreased variation in the neighboring loci, known as a selective sweep. When the region containing this pattern is compared to another population with no history of selection, a rise in variance of allele frequencies between populations is observed. One challenge presented by large genome-wide datasets is the ability to differentiate between patterns that are remnants of natural selection from those expected to arise at random and/or as a consequence of selectively neutral demographic forces acting in the population. Findings: SmileFinder is a simple program that looks for diversity and divergence patterns consistent with selection sweeps by evaluating allele frequencies in windows, including neighboring loci from two or more populations of a diploid species against the genome-wide neutral expectation. The program calculates the mean of heterozygosity and FST in a set of sliding windows of incrementally increasing sizes, and then builds a resampled distribution (the baseline) of random multi-locus sets matched to the sizes of sliding windows, using an unrestricted sampling. Percentiles of the values in the sliding windows are derived from the superimposed resampled distribution. The resampling can easily be scaled from 1 K to 100 M; the higher the number, the more precise the percentiles ascribed to the extreme observed values. Conclusions: The output from SmileFinder can be used to plot percentile values to look for population diversity and divergence patterns that may suggest past actions of positive selection along chromosome maps, and to compare lists of suspected candidate genes under random gene sets to test for the overrepresentation of these patterns among gene categories. Both applications of the algorithm have already been used in published studies. Here we present a publicly available, open source program that will serve as a useful tool for preliminary scans of selection using worldwide databases of human genetic variation, as well as population datasets for many non-human species, from which such data is rapidly emerging with the advent of new genotyping and sequencing technologies

Sensitivity Analysis for Multidisciplinary Systems (SAMS)

This report describes the research conducted under an interagency collaboration agreement between the Aerospace Systems Directorate of the Air Force Research Laboratory (AFRL/RQ) and the Computational AeroSciences Branch of NASA Langley (NASA LaRC). Both organizations have a long-term goal of developing a modular computational system for coupling fluids and structures to enable both analysis and optimization of aerospace vehicles. Ultimately, the system should support multiple solvers within the fluid and structure domains to allow the best combination for the task at hand, as well as to allow for institutional preferences of specific software components. Towards this goal, the current research was focused on enhancing the existing modal aeroelastic analysis in the NASA FUN3D (Fully-UNstructured three-dimensional CFD (Computational Fluid Dynamics) code) software (Biedron et al. 2018), as well as developing new aeroelastic analysis and optimization capabilities based on a non-linear finite-element method. The methods and enhancements described in this document pertain to FUN3D Version 13.4

Weighing the Giants - I. Weak-lensing masses for 51 massive galaxy clusters: project overview, data analysis methods and cluster images

This is the first in a series of papers in which we measure accurate weak-lensing masses for 51 of the most X-ray luminous galaxy clusters known at redshifts 0.15<z<0.7, in order to calibrate X-ray and other mass proxies for cosmological cluster experiments. The primary aim is to improve the absolute mass calibration of cluster observables, currently the dominant systematic uncertainty for cluster count experiments. Key elements of this work are the rigorous quantification of systematic uncertainties, high-quality data reduction and photometric calibration, and the "blind" nature of the analysis to avoid confirmation bias. Our target clusters are drawn from RASS X-ray catalogs, and provide a versatile calibration sample for many aspects of cluster cosmology. We have acquired wide-field, high-quality imaging using the Subaru and CFHT telescopes for all 51 clusters, in at least three bands per cluster. For a subset of 27 clusters, we have data in at least five bands, allowing accurate photo-z estimates of lensed galaxies. In this paper, we describe the cluster sample and observations, and detail the processing of the SuprimeCam data to yield high-quality images suitable for robust weak-lensing shape measurements and precision photometry. For each cluster, we present wide-field color optical images and maps of the weak-lensing mass distribution, the optical light distribution, and the X-ray emission, providing insights into the large-scale structure in which the clusters are embedded. We measure the offsets between X-ray centroids and Brightest Cluster Galaxies in the clusters, finding these to be small in general, with a median of 20kpc. For offsets <100kpc, weak-lensing mass measurements centered on the BCGs agree well with values determined relative to the X-ray centroids; miscentering is therefore not a significant source of systematic uncertainty for our mass measurements. [abridged]Comment: 26 pages, 19 figures (Appendix C not included). Accepted after minor revisio

Taking into account sensory knowledge: the case of geo-techologies for children with visual impairments

This paper argues for designing geo-technologies supporting non-visual sensory knowledge. Sensory knowledge refers to the implicit and explicit knowledge guiding our uses of our senses to understand the world. To support our argument, we build on an 18 months field-study on geography classes for primary school children with visual impairments. Our findings show (1) a paradox in the use of non-visual sensory knowledge: described as fundamental to the geography curriculum, it is mostly kept out of school; (2) that accessible geo-technologies in the literature mainly focus on substituting vision with another modality, rather than enabling teachers to build on children's experiences; (3) the importance of the hearing sense in learning about space. We then introduce a probe, a wrist-worn device enabling children to record audio cues during field-trips. By giving importance to children's hearing skills, it modified existing practices and actors' opinions on non-visual sensory knowledge. We conclude by reflecting on design implications, and the role of technologies in valuing diverse ways of understanding the world

Lensing in the Blue II: Estimating the Sensitivity of Stratospheric Balloons to Weak Gravitational Lensing

The Superpressure Balloon-borne Imaging Telescope (SuperBIT) is a diffraction-limited, wide-field, 0.5 m, near-infrared to near-ultraviolet observatory designed to exploit the stratosphere's space-like conditions. SuperBIT's 2023 science flight will deliver deep, blue imaging of galaxy clusters for gravitational lensing analysis. In preparation, we have developed a weak lensing measurement pipeline with modern algorithms for PSF characterization, shape measurement, and shear calibration. We validate our pipeline and forecast SuperBIT survey properties with simulated galaxy cluster observations in SuperBIT's near-UV and blue bandpasses. We predict imaging depth, galaxy number (source) density, and redshift distribution for observations in SuperBIT's three bluest filters; the effect of lensing sample selections is also considered. We find that in three hours of on-sky integration, SuperBIT can attain a depth of b = 26 mag and a total source density exceeding 40 galaxies per square arcminute. Even with the application of lensing-analysis catalog selections, we find b-band source densities between 25 and 30 galaxies per square arcminute with a median redshift of z = 1.1. Our analysis confirms SuperBIT's capability for weak gravitational lensing measurements in the blue.Comment: Submitted to Astronomical Journa