180 research outputs found
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High integrity hardware-software codesign
Programmable logic devices (PLDs) are increasing in complexity and speed, and are being used as important components in safety-critical systems. Methods for developing high-integrity software for these systems are well-known, but this is not true for programmable logic. We propose a process for developing a system incorporating software and PLDs, suitable for safety critical systems of the highest levels of integrity. This process incorporates the use of Synchronous Receptive Process Theory as a semantic basis for specifying and proving properties of programs executing on PLDs, and extends the use of SPARK Ada from a programming language for safety-critical systems software to cover the interface between software and programmable logic. We have validated this approach through the specification and development of a substantial safety-critical system incorporating both software and programmable logic components, and the development of tools to support this work. This enables us to claim that the methods demonstrated are not only feasible but also scale up to realistic system sizes, allowing development of such safety-critical software-hardware systems to the levels required by current system safety standards
Dynamic feathering: minimising blending artefacts in view-dependent rendering
Conventional view-dependent texture mapping techniques produce composite images by blending subsets of input images, weighted according to their relative influence at the rendering viewpoint, over regions where the views overlap. Geometric or camera calibration errors often result in a los s of detail due to blurring or double exposure artefacts which tends to be exacerbated by the number of blending views considered. We propose a novel view-dependent rendering technique which optimises the blend region dynamically at rendering time, and reduces the adverse effects of camera calibration or geometric errors otherwise observed. The technique has been successfully integrated in a rendering pipeline which operates at interactive frame rates. Improvement over state-of-the-art view-dependent texture mapping techniques are illustrated on a synthetic scene as well as real imagery of a large scale outdoor scene where large camera calibration and geometric errors are present
Partially Randomized, Non-Blinded Trial of DNA and MVA Therapeutic Vaccines Based on Hepatitis B Virus Surface Protein for Chronic HBV Infection
BACKGROUND: Chronic HBV infects 350 million people causing cancer and liver failure. We aimed to assess the safety and efficacy of plasmid DNA (pSG2.HBs) vaccine, followed by recombinant modified vaccinia virus Ankara (MVA.HBs), encoding the surface antigen of HBV as therapy for chronic HBV. A secondary goal was to characterize the immune responses. METHODS: Firstly 32 HBV e antigen negative (eAg(-)) participants were randomly assigned to one of four groups: to receive vaccines alone, lamivudine (3TC) alone, both, or neither. Later 16 eAg(+) volunteers in two groups received either 3TC alone or both 3TC and vaccines. Finally, 12 eAg(-) and 12 eAg(+) subjects were enrolled into higher-dose treatment groups. Healthy but chronically HBV-infected males between the ages of 15-25 who lived in the western part of The Gambia were eligible. Participants in some groups received 1 mg or 2 mg of pSG2.HBs intramuscularly twice followed by 5×10(7) pfu or 1.5×10(8) pfu of MVA.HBs intradermally at 3-weekly intervals with or without concomitant 3TC for 11-14 weeks. Intradermal rabies vaccine was administered to a negative control group. Safety was assessed clinically and biochemically. The primary measure of efficacy was a quantitative PCR assay of plasma HBV. Immunity was assessed by IFN-γ ELISpot and intracellular cytokine staining. RESULTS: Mild local and systemic adverse events were observed following the vaccines. A small shiny scar was observed in some cases after MVA.HBs. There were no significant changes in AST or ALT. HBeAg was lost in one participant in the higher-dose group. As expected, the 3TC therapy reduced viraemia levels during therapy, but the prime-boost vaccine regimen did not reduce the viraemia. The immune responses were variable. The majority of IFN-γ was made by antigen non-specific CD16(+) cells (both CD3(+) and CD3(-)). CONCLUSIONS: The vaccines were well tolerated but did not control HBV infection. TRIAL REGISTRATION: ISRCTN ISRCTN67270384
CD4 intragenic SNPs associate with HIV-2 plasma viral load and CD4 count in a community-based study from Guinea-Bissau, West Africa.
OBJECTIVES: The human genetics of HIV-2 infection and disease progression is understudied. Therefore, we studied the effect of variation in 2 genes that encode products critical to HIV pathogenesis and disease progression: CD4 and CD209. DESIGN: This cross-sectional study consisted of 143 HIV-2, 30 HIV-1 + HIV-2 and 29 HIV-1-infected subjects and 194 uninfected controls recruited from rural Guinea-Bissau. METHODS: We genotyped 14 CD4 and 4 CD209 single nucleotide polymorphisms (SNPs) that were tested for association with HIV infection, HIV-2 plasma viral load (high vs. low), and CD4 T-cell count (high vs. low). RESULTS: The most significant association was between a CD4 haplotype rs11575097-rs10849523 and high viral load [odds ratio (OR): = 2.37, 95% confidence interval (CI): 1.35 to 4.19, P = 0.001, corrected for multiple testing], suggesting increased genetic susceptibility to HIV-2 disease progression for individuals carrying the high-risk haplotype. Significant associations were also observed at a CD4 SNP (rs2255301) with HIV-2 infection (OR: = 2.36, 95% CI: 1.19 to 4.65, P = 0.01) and any HIV infection (OR: = 2.50, 95% CI: 1.34 to 4.69, P = 0.004). CONCLUSIONS: Our results support a role of CD4 polymorphisms in HIV-2 infection, in agreement with recent data showing that CD4 gene variants increase risk to HIV-1 in Kenyan female sex workers. These findings indicate at least some commonality in HIV-1 and HIV-2 susceptibility
Instrumental performance and results from testing of the BLAST-TNG receiver, submillimeter optics, and MKID arrays
Polarized thermal emission from interstellar dust grains can be used to map
magnetic fields in star forming molecular clouds and the diffuse interstellar
medium (ISM). The Balloon-borne Large Aperture Submillimeter Telescope for
Polarimetry (BLASTPol) flew from Antarctica in 2010 and 2012 and produced
degree-scale polarization maps of several nearby molecular clouds with
arcminute resolution. The success of BLASTPol has motivated a next-generation
instrument, BLAST-TNG, which will use more than 3000 linear polarization
sensitive microwave kinetic inductance detectors (MKIDs) combined with a 2.5m
diameter carbon fiber primary mirror to make diffraction-limited observations
at 250, 350, and 500 m. With 16 times the mapping speed of BLASTPol,
sub-arcminute resolution, and a longer flight time, BLAST-TNG will be able to
examine nearby molecular clouds and the diffuse galactic dust polarization
spectrum in unprecedented detail. The 250 m detector array has been
integrated into the new cryogenic receiver, and is undergoing testing to
establish the optical and polarization characteristics of the instrument.
BLAST-TNG will demonstrate the effectiveness of kilo-pixel MKID arrays for
applications in submillimeter astronomy. BLAST-TNG is scheduled to fly from
Antarctica in December 2017 for 28 days and will be the first balloon-borne
telescope to offer a quarter of the flight for "shared risk" observing by the
community.Comment: Presented at SPIE Millimeter, Submillimeter, and Far-Infrared
Detectors and Instrumentation for Astronomy VIII, June 29th, 201
The First Hour of Extra-galactic Data of the Sloan Digital Sky Survey Spectroscopic Commissioning: The Coma Cluster
On 26 May 1999, one of the Sloan Digital Sky Survey (SDSS) fiber-fed
spectrographs saw astronomical first light. This was followed by the first
spectroscopic commissioning run during the dark period of June 1999. We present
here the first hour of extra-galactic spectroscopy taken during these early
commissioning stages: an observation of the Coma cluster of galaxies. Our data
samples the Southern part of this cluster, out to a radius of 1.5degrees and
thus fully covers the NGC 4839 group. We outline in this paper the main
characteristics of the SDSS spectroscopic systems and provide redshifts and
spectral classifications for 196 Coma galaxies, of which 45 redshifts are new.
For the 151 galaxies in common with the literature, we find excellent agreement
between our redshift determinations and the published values. As part of our
analysis, we have investigated four different spectral classification
algorithms: spectral line strengths, a principal component decomposition, a
wavelet analysis and the fitting of spectral synthesis models to the data. We
find that a significant fraction (25%) of our observed Coma galaxies show signs
of recent star-formation activity and that the velocity dispersion of these
active galaxies (emission-line and post-starburst galaxies) is 30% larger than
the absorption-line galaxies. We also find no active galaxies within the
central (projected) 200 h-1 Kpc of the cluster. The spatial distribution of our
Coma active galaxies is consistent with that found at higher redshift for the
CNOC1 cluster survey. Beyond the core region, the fraction of bright active
galaxies appears to rise slowly out to the virial radius and are randomly
distributed within the cluster with no apparent correlation with the potential
merger of the NGC 4839 group. [ABRIDGED]Comment: Accepted in AJ, 65 pages, 20 figures, 5 table
Quantitative association tests of immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa.
There is now considerable evidence that host genetic factors are important in determining the outcome of infection with Mycobacterium tuberculosis (MTB). The aim of this study was to assess the role of several candidate genes in the variation observed in the immune responses to MTB antigens. In-vitro assays of T-cell proliferation, an in-vivo intradermal delayed hypersensitivity response; cytokine and antibody secretions to several mycobacterial peptide antigens were assessed in healthy, but exposed, West African twins. Candidate gene polymorphisms were typed in the NRAMP1, Vitamin D receptor, IL10, IL4, IL4 receptor and CTLA-4 genes. Variants of the loci IL10 (-1082 G/A), CTLA-4 (49 A/G) and the IL4 receptor (128 A/G) showed significant associations with immune responses to several antigens. T-cell proliferative responses and antibody responses were reduced, TNF-alpha responses were increased for subjects with the CTLA-4 G allele. The T-cell proliferative responses of subjects with IL10 GA and GG genotypes differed significantly. IL4 receptor AG and GG genotypes also showed significant differences in their T-cell proliferative responses to MTB antigens. These results yield a greater understanding of the genetic mechanisms that underlie the immune responses in tuberculosis and have implications for the design of therapeutic interventions
Characterization, deployment, and in-flight performance of the BLAST-TNG cryogenic receiver
The Next Generation Balloon-borne Large Aperture Submillimeter Telescope
(BLAST-TNG) is a submillimeter polarimeter designed to map interstellar dust
and galactic foregrounds at 250, 350, and 500 microns during a 24-day Antarctic
flight. The BLAST-TNG detector arrays are comprised of 918, 469, and 272 MKID
pixels, respectively. The pixels are formed from two orthogonally oriented,
crossed, linear-polarization sensitive MKID antennae. The arrays are cooled to
sub 300mK temperatures and stabilized via a closed cycle He sorption fridge
in combination with a He vacuum pot. The detectors are read out through a
combination of the second-generation Reconfigurable Open Architecture Computing
Hardware (ROACH2) and custom RF electronics designed for BLAST-TNG. The
firmware and software designed to readout and characterize these detectors was
built from scratch by the BLAST team around these detectors, and has been
adapted for use by other MKID instruments such as TolTEC and OLIMPO. We present
an overview of these systems as well as in-depth methodology of the
ground-based characterization and the measured in-flight performance.Comment: Presented at SPIE Millimeter, Submillimeter, and Far-Infrared
Detectors and Instrumentation for Astronomy X, December 13-18, 202
Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
From Springer Nature via Jisc Publications RouterHistory: received 2020-09-28, accepted 2021-06-30, registration 2021-07-13, pub-electronic 2021-07-30, online 2021-07-30, collection 2021-12Publication status: PublishedFunder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/L002744/1, MR/T016809/1, MR/L002744/1, MR/L002744/1Funder: Diabetes UK; doi: http://dx.doi.org/10.13039/501100000361; Grant(s): 15/0005283, 15/0005283Abstract: Diabetes mellitus (DM) is the leading cause of chronic kidney disease and diabetic nephropathy is widely studied. In contrast, the pathobiology of diabetic urinary bladder disease is less understood despite dysfunctional voiding being common in DM. We hypothesised that diabetic cystopathy has a characteristic molecular signature. We therefore studied bladders of hyperglycaemic and polyuric rats with streptozotocin (STZ)-induced DM. Sixteen weeks after induction of DM, as assessed by RNA arrays, wide-ranging changes of gene expression occurred in DM bladders over and above those induced in bladders of non-hyperglycaemic rats with sucrose-induced polyuria. The altered transcripts included those coding for extracellular matrix regulators and neural molecules. Changes in key genes deregulated in DM rat bladders were also detected in db/db mouse bladders. In DM rat bladders there was reduced birefringent collagen between detrusor muscle bundles, and atomic force microscopy showed a significant reduction in tissue stiffness; neither change was found in bladders of sucrose-treated rats. Thus, altered extracellular matrix with reduced tissue rigidity may contribute to voiding dysfunction in people with long-term DM. These results serve as an informative stepping stone towards understanding the complex pathobiology of diabetic cystopathy
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