729 research outputs found

    Genomic evidence of pre-invasive clonal expansion, dispersal and progression in bronchial dysplasia

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    The term ‘field cancerization’ is used to describe an epithelial surface that has a propensity to develop cancerous lesions, and in the case of the aerodigestive tract this is often as a result of chronic exposure to carcinogens in cigarette smoke 1, 2. The clinical endpoint is the development of multiple tumours, either simultaneously or sequentially in the same epithelial surface. The mechanisms underlying this process remain unclear; one possible explanation is that the epithelium is colonized by a clonal population of cells that are at increased risk of progression to cancer. We now address this possibility in a short case series, using individual genomic events as molecular biomarkers of clonality. In squamous lung cancer the most common genomic aberration is 3q amplification. We use a digital PCR technique to assess the clonal relationships between multiple biopsies in a longitudinal bronchoscopic study, using amplicon boundaries as markers of clonality. We demonstrate that clonality can readily be defined by these analyses and confirm that field cancerization occurs at a pre-invasive stage and that pre-invasive lesions and subsequent cancers are clonally related. We show that while the amplicon boundaries can be shared between different biopsies, the degree of 3q amplification and the internal structure of the 3q amplicon varies from lesion to lesion. Finally, in this small cohort, the degree of 3q amplification corresponds to clinical progression. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

    The Effects of Air and Underwater Blast on Composite Sandwich Panels and Tubular Laminate Structures

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    The resistance of glass-fibre reinforced polymer (GFRP) sandwich panels and laminate tubes to blast in air and underwater environments has been studied. Procedures for monitoring the structural response of such materials during blast events have been devised. High-speed photography was employed during the air-blast loading of GFRP sandwich panels, in conjunction with digital image correlation (DIC), to monitor the deformation of these structures under shock loading. Failure mechanisms have been revealed by using DIC and confirmed in post-test sectioning. Strain gauges were used to monitor the structural response of similar sandwich materials and GFRP tubular laminates during underwater shocks. The effect of the backing medium (air or water) of the target facing the shock has been identified during these studies. Mechanisms of failure have been established such as core crushing, skin/core cracking, delamination and fibre breakage. Strain gauge data supported the mechanisms for such damage. These studies were part of a research programme sponsored by the Office of Naval Research (ONR) investigating blast loading of composite naval structures. The full-scale experimental results presented here will aid and assist in the development of analytical and computational models. Furthermore, it highlights the importance of support and boundary conditions with regards to blast resistant design

    BAC-HAPPY mapping (BAP mapping): a new and efficient protocol for physical mapping

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    Physical and linkage mapping underpin efforts to sequence and characterize the genomes of eukaryotic organisms by providing a skeleton framework for whole genome assembly. Hitherto, linkage and physical “contig” maps were generated independently prior to merging. Here, we develop a new and easy method, BAC HAPPY MAPPING (BAP mapping), that utilizes BAC library pools as a HAPPY mapping panel together with an Mbp-sized DNA panel to integrate the linkage and physical mapping efforts into one pipeline. Using Arabidopsis thaliana as an exemplar, a set of 40 Sequence Tagged Site (STS) markers spanning ~10% of chromosome 4 were simultaneously assembled onto a BAP map compiled using both a series of BAC pools each comprising 0.7x genome coverage and dilute (0.7x genome) samples of sheared genomic DNA. The resultant BAP map overcomes the need for polymorphic loci to separate genetic loci by recombination and allows physical mapping in segments of suppressed recombination that are difficult to analyze using traditional mapping techniques. Even virtual “BAC-HAPPY-mapping” to convert BAC landing data into BAC linkage contigs is possible.Giang T. H. Vu, Paul H. Dear, Peter D. S. Caligari and Mike J. Wilkinso

    Compressive strength after blast of sandwich composite materials

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    Composite sandwich materials have yet to be widely adopted in the construction of naval vessels despite their excellent strength-to-weight ratio and low radar return. One barrier to their wider use is our limited understanding of their performance when subjected to air blast. This paper focuses on this problem and specifically the strength remaining after damage caused during an explosion. Carbon-fibre-reinforced polymer (CFRP) composite skins on a styrene–acrylonitrile (SAN) polymer closed-cell foam core are the primary composite system evaluated. Glass-fibre-reinforced polymer (GFRP) composite skins were also included for comparison in a comparable sandwich configuration. Full-scale blast experiments were conducted, where 1.6×1.3 m sized panels were subjected to blast of a Hopkinson–Cranz scaled distance of 3.02 m kg−1/3, 100 kg TNT equivalent at a stand-off distance of 14 m. This explosive blast represents a surface blast threat, where the shockwave propagates in air towards the naval vessel. Hopkinson was the first to investigate the characteristics of this explosive air-blast pulse (Hopkinson 1948 Proc. R. Soc. Lond. A 89, 411–413 (doi:10.1098/rspa.1914.0008)). Further analysis is provided on the performance of the CFRP sandwich panel relative to the GFRP sandwich panel when subjected to blast loading through use of high-speed speckle strain mapping. After the blast events, the residual compressive load-bearing capacity is investigated experimentally, using appropriate loading conditions that an in-service vessel may have to sustain. Residual strength testing is well established for post-impact ballistic assessment, but there has been less research performed on the residual strength of sandwich composites after blast

    A provisional database for the silicon content of foods in the United Kingdom

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    Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma&ndash;optical emission spectrometry following microwave-assisted digestion with nitric acid and H2O2. The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.<br /

    Considering the impact of situation-specific motivations and constraints in the design of naturally ventilated and hybrid buildings

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    A simple logical model of the interaction between a building and its occupants is presented based on the principle that if free to do so, people will adjust their posture, clothing or available building controls (windows, blinds, doors, fans, and thermostats) with the aim of achieving or restoring comfort and reducing discomfort. These adjustments are related to building design in two ways: first the freedom to adjust depends on the availability and ease-of-use of control options; second the use of controls affects building comfort and energy performance. Hence it is essential that these interactions are considered in the design process. The model captures occupant use of controls in response to thermal stimuli (too warm, too cold etc.) and non-thermal stimuli (e.g. desire for fresh air). The situation-specific motivations and constraints on control use are represented through trigger temperatures at which control actions occur, motivations are included as negative constraints and incorporated into a single constraint value describing the specifics of each situation. The values of constraints are quantified for a range of existing buildings in Europe and Pakistan. The integration of the model within a design flow is proposed and the impact of different levels of constraints demonstrated. It is proposed that to minimise energy use and maximise comfort in naturally ventilated and hybrid buildings the designer should take the following steps: 1. Provide unconstrained low energy adaptive control options where possible, 2. Avoid problems with indoor air quality which provide motivations for excessive ventilation rates, 3. Incorporate situation-specific adaptive behaviour of occupants in design simulations, 4. Analyse the robustness of designs against variations in patterns of use and climate, and 5. Incorporate appropriate comfort standards into the operational building controls (e.g. BEMS)

    Sandwich Panel Cores for Blast Applications: Materials and Graded Density

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    Sandwich composites are of interest in marine applications due to their high strength-to-weight ratio and tailorable mechanical properties, but their resistance to air blast loading is not well understood. Full-scale 100 kg TNT equivalent air blast testing at a 15 m stand-off distance was performed on glass-fibre reinforced polymer (GFRP) sandwich panels with polyvinyl chloride (PVC); polymethacrylimid (PMI); and styrene acrylonitrile (SAN) foam cores, all possessing the same thickness and density. Further testing was performed to assess the blast resistance of a sandwich panel containing a stepwise graded density SAN foam core, increasing in density away from the blast facing side. Finally a sandwich panel containing compliant polypropylene (PP) fibres within the GFRP front face-sheet, was subjected to blast loading with the intention of preventing front face-sheet cracking during blast. Measurements of the sandwich panel responses were made using high-speed digital image correlation (DIC), and post-blast damage was assessed by sectioning the sandwich panels and mapping the damage observed. It was concluded that all cores are effective in improving blast tolerance and that the SAN core was the most blast tolerant out of the three foam polymer types, with the DIC results showing a lower deflection measured during blast, and post-blast visual inspections showing less damage suffered. By grading the density of the core it was found that through thickness crack propagation was mitigated, as well as damage in the higher density foam layers, thus resulting in a smoother back face-sheet deflection profile. By incorporating compliant PP fibres into the front face-sheet, cracking was prevented in the GFRP, despite damage being present in the core and the interfaces between the core and face-sheets

    Comparative Genome Analysis Reveals Divergent Genome Size Evolution in a Carnivorous Plant Genus

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    The C-value paradox remains incompletely resolved after >40 yr and is exemplified by 2,350-fold variation in genome sizes of flowering plants. The carnivorous Lentibulariaceae genus , displaying a 25-fold range of genome sizes, is a promising subject to study mechanisms and consequences of evolutionary genome size variation. Applying genomic, phylogenetic, and cytogenetic approaches, we uncovered bidirectional genome size evolution within the genus . The Steyerm. genome (86 Mbp) has probably shrunk by retroelement silencing and deletion-biased double-strand break (DSB) repair, from an ancestral size of 400 to 800 Mbp to become one of the smallest among flowering plants. The Stapf genome has expanded by whole-genome duplication (WGD) and retrotransposition to 1550 Mbp. became allotetraploid after the split from the clade ∼29 Ma. A. St.-Hil. (179 Mbp), a close relative of , proved to be a recent (auto)tetraploid. Our analyses suggest a common ancestor of the genus a with an intermediate 1C value (400–800 Mbp) and subsequent rapid genome size evolution in opposite directions. Many abundant repeats of the larger genome are absent in the smaller, casting doubt on their functionality for the organism, while recurrent WGD seems to safeguard against the loss of essential elements in the face of genome shrinkage. We cannot identify any consistent differences in habitat or life strategy that correlate with genome size changes, raising the possibility that these changes may be selectively neutral

    A numerical method for predicting the deformation of crazed laminated windows under blast loading

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    The design of laminated glazing for blast resistance is significantly complicated by the post-crack behaviour of glass layers. In this research, a novel numerical method based on a semi-analytical energy model is proposed for the post-crack behaviour of crazed panes. To achieve this, the non-homogenous glass cracks patterns observed in literature experimental and analytical work was taken into consideration. It was assumed that, after the glass crazing, further deformations would occur in the cracked edge areas, whilst the central window surface would remain largely undeformed. Therefore, different internal work expressions were formulated for each zone and were then combined in the overall model. The resulting differential equation was then solved numerically. The results obtained were compared with data from four experimental full-scale blast tests for validation. Three of these blast tests (Tests 1–3) were presented previously (Hooper et al., 2012) on 1.5 × 1.2 m laminated glazing samples made up with two 3 mm glass layers and a central 1.52 mm PVB membrane, using a 15 and 30 kg charge masses (TNT equivalent) at 13–16 m stand-off. The fourth blast test (Test 4) was conducted on a larger 3.6 × 2.0 m pane of 13.52 mm thickness, using a 100 kg charge mass (TNT equivalent) at a 17 m stand-off. All blast tests employed the Digital Image Correlation (DIC) technique to obtain 3D out-of-plane deflections and strains.The proposed analytical method reproduced the experimental deflection profiles, with the best estimates obtained for the more severe loading cases. Reaction forces were also compared with experimental estimates. The predictive ability of the proposed method could permit more accurate designs to be produced rapidly, improving structures resistance to such loadings
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