2,691 research outputs found

    Shape computations without compositions

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    Parametric CAD supports design explorations through generative methods which compose and transform geometric elements. This paper argues that elementary shape computations do not always correspond to valid compositional shape structures. In many design cases generative rules correspond to compositional structures, but for relatively simple shapes and rules it is not always possible to assign a corresponding compositional structure of parts which account for all operations of the computation. This problem is brought into strong relief when design processes generate multiple compositions according to purpose, such as product structure, assembly, manufacture, etc. Is it possible to specify shape computations which generate just these compositions of parts or are there additional emergent shapes and features? In parallel, combining two compositions would require the associated combined computations to yield a valid composition. Simple examples are presented which throw light on the issues in integrating different product descriptions (i.e. compositions) within parametric CAD

    The SOAR Gravitational Arc Survey - I: Survey overview and photometric catalogs

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    We present the first results of the SOAR (Southern Astrophysical Research) Gravitational Arc Survey (SOGRAS). The survey imaged 47 clusters in two redshift intervals centered at z=0.27z=0.27 and z=0.55z=0.55, targeting the richest clusters in each interval. Images were obtained in the g′g', r′r' and i′i' bands using the SOAR Optical Imager (SOI), with a median seeing of 0.83, 0.76 and 0.71 arcsec, respectively, in these filters. Most of the survey clusters are located within the Sloan Digital Sky Survey (SDSS) Stripe 82 region and all of them are in the SDSS footprint. Photometric calibration was therefore performed using SDSS stars located in our SOI fields. We reached for galaxies in all fields the detection limits of g∼23.5g \sim 23.5, r∼23r \sim 23 and i∼22.5i \sim 22.5 for a signal-to-noise ratio (S/N) = 3. As a by-product of the image processing, we generated a source catalogue with 19760 entries, the vast majority of which are galaxies, where we list their positions, magnitudes and shape parameters. We compared our galaxy shape measurements to those of local galaxies and concluded that they were not strongly affected by seeing. From the catalogue data, we are able to identify a red sequence of galaxies in most clusters in the lower zz range. We found 16 gravitational arc candidates around 8 clusters in our sample. They tend to be bluer than the central galaxies in the lensing cluster. A preliminary analysis indicates that ∼10\sim 10% of the clusters have arcs around them, with a possible indication of a larger efficiency associated to the high-zz systems when compared to the low-zz ones. Deeper follow-up images with Gemini strengthen the case for the strong lensing nature of the candidates found in this survey.Comment: 17 pages, 11 figures (most of them multi-panel) MNRAS (2013

    Seiberg duality, quiver gauge theories, and Ihara's zeta function

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    We study Ihara’s zeta function for graphs in the context of quivers arising from gauge theories, especially under Seiberg duality transformations. The distribution of poles is studied as we proceed along the duality tree, in light of the weak and strong graph versions of the Riemann Hypothesis. As a by-product, we find a refined version of Ihara’s zeta function to be the generating function for the generic superpotential of the gauge theory

    A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

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    © 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

    Functional limit theorems for random regular graphs

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    Consider d uniformly random permutation matrices on n labels. Consider the sum of these matrices along with their transposes. The total can be interpreted as the adjacency matrix of a random regular graph of degree 2d on n vertices. We consider limit theorems for various combinatorial and analytical properties of this graph (or the matrix) as n grows to infinity, either when d is kept fixed or grows slowly with n. In a suitable weak convergence framework, we prove that the (finite but growing in length) sequences of the number of short cycles and of cyclically non-backtracking walks converge to distributional limits. We estimate the total variation distance from the limit using Stein's method. As an application of these results we derive limits of linear functionals of the eigenvalues of the adjacency matrix. A key step in this latter derivation is an extension of the Kahn-Szemer\'edi argument for estimating the second largest eigenvalue for all values of d and n.Comment: Added Remark 27. 39 pages. To appear in Probability Theory and Related Field

    Orientation bias of optically selected galaxy clusters and its impact on stacked weak-lensing analyses

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    Weak-lensing measurements of the averaged shear profiles of galaxy clusters binned by some proxy for cluster mass are commonly converted to cluster mass estimates under the assumption that these cluster stacks have spherical symmetry. In this paper, we test whether this assumption holds for optically selected clusters binned by estimated optical richness. Using mock catalogues created from N-body simulations populated realistically with galaxies, we ran a suite of optical cluster finders and estimated their optical richness. We binned galaxy clusters by true cluster mass and estimated optical richness and measure the ellipticity of these stacks. We find that the processes of optical cluster selection and richness estimation are biased, leading to stacked structures that are elongated along the line of sight. We show that weak-lensing alone cannot measure the size of this orientation bias. Weak-lensing masses of stacked optically selected clusters are overestimated by up to 3–6 per cent when clusters can be uniquely associated with haloes. This effect is large enough to lead to significant biases in the cosmological parameters derived from large surveys like the Dark Energy Survey, if not calibrated via simulations or fitted simultaneously. This bias probably also contributes to the observed discrepancy between the observed and predicted Sunyaev–Zel’dovich signal of optically selected clusters

    Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

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    AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

    Exploiting inflammation for therapeutic gain in pancreatic cancer

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    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

    Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

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    Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)
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