2,016 research outputs found

    Effects of fiber, matrix, and interphase on carbon fiber composite compression strength

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    The major goal of this project was to obtain basic information on compression failure properties of carbon fiber composites. To do this, we investigated fiber effects, matrix effects, and fiber/matrix interface effects. Using each of nine fiber types, we prepared embedded single-fiber specimens, single-ply specimens, and full laminates. From the single-fiber specimens, in addition to the standard fragmentation test analysis, we were able to use the low crack density data to provide information about the distribution of fiber flaws. The single-ply specimens provided evidence of a correlation between the size of kink band zones and the quality of the interface. Results of the laminate compression experiments mostly agreed with the results from single-ply experiments, although the ultimate compression strengths of laminates were higher. Generally, these experiments showed a strong effect of interfacial properties. Matrix effects were examined using laminates subjected to precracking under mixed-mode loading conditions. A large effect of precracking conditions on the mode 1 toughness of the laminates was found. In order to control the properties of the fiber/matrix interface, we prepared composites of carbon fiber and polycarbonate and subjected these to annealing. The changes in interfacial properties directly correlated with changes in compression strength

    Human involucrin promoter mediates repression-resistant and compartment-specific LEKTI expression

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    Gene-modified skin grafts, produced through gene transfer to human keratinocyte stem cells, offer the possibility of therapeutic benefit for inherited skin diseases. We have previously described efficient lentiviral vector–mediated gene transfer to keratinocyte stem cells and the generation of human skin grafts for the inherited skin disease, Netherton syndrome, which arises due to mutations in serine protease inhibitor Kazal-type 5 (SPINK5). Vectors incorporating an internal murine retroviral–derived promoter [spleen focus-forming virus (SFFV)] in combination with a codon-optimized SPINK5 transgene supported high levels of reconstitution and robust correction of skin architecture. Subsequent longer-term experiments have uncovered unanticipated silencing phenomena, with loss of SPINK5 gene expression over time. The inadvertent introduction of CpG sites during codon optimization appears to have rendered vectors susceptible to silencing due to methylation across the promoter–transgene boundary. Substitution of the methylation-susceptible SFFV promoter with a 572-bp minimal human involucrin promoter (INVOp), which encodes very few CpG sites, prevented repression of the SPINK5 transgene and resulted in durable and highly compartment-specific reconstitution of lympho-epithelial Kazal-type–related inhibitor (LEKTI) in human skin grafted onto immunodeficient mice.We conclude that skin grafts modified with lentiviral vectors encoding INVOp offer a suitable platform for therapeutic gene therapy in Netherton syndrome, and our experience highlights unanticipated effects of transgene codon optimization

    "It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

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    Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base

    Evolution of high pathogenicity of H5 avian influenza virus: haemagglutinin cleavage site selection of reverse-genetics mutants during passage in chickens

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    Low pathogenicity avian influenza viruses (LPAIVs) are generally asymptomatic in their natural avian hosts. LPAIVs can evolve into highly pathogenic forms, which can affect avian and human populations with devastating consequences. The switch to highly pathogenic avian influenza virus (HPAIV) from LPAIV precursors requires the acquisition of multiple basic amino acids in the haemagglutinin cleavage site (HACS) motif. Through reverse genetics of an H5N1 HPAIV, and experimental infection of chickens, we determined that viruses containing five or more basic amino acids in the HACS motif were preferentially selected over those with three to four basic amino acids, leading to rapid replacement with virus types containing extended HACS motifs. Conversely, viruses harbouring low pathogenicity motifs containing two basic amino acids did not readily evolve to extended forms, suggesting that a single insertion of a basic amino acid into the cleavage site motif of low-pathogenic viruses may lead to escalating selection for extended motifs. Our results may explain why mid-length forms are rarely detected in nature. The stability of the short motif suggests that pathogenicity switching may require specific conditions of intense selection pressure (such as with high host density) to boost selection of the initial mid-length HACS forms

    Investigating the Bivalve Tree of Life -- an exemplar-based approach combining molecular and novel morphological characters.

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    To re-evaluate the relationships of the major bivalve lineages, we amassed detailed morpho-anatomical, ultrastructural and molecular sequence data for a targeted selection of exemplar bivalves spanning the phylogenetic diversity of the class. We included molecular data for 103 bivalve species (up to five markers) and also analysed a subset of taxa with four additional nuclear protein-encoding genes. Novel as well as historically employed morphological characters were explored, and we systematically disassembled widely used descriptors such as gill and stomach ‘types’. Phylogenetic analyses, conducted using parsimony direct optimisation and probabilistic methods on static alignments (maximum likelihood and Bayesian inference) of the molecular data, both alone and in combination with morphological characters, offer a robust test of bivalve relationships. A calibrated phylogeny also provided insights into the tempo of bivalve evolution. Finally, an analysis of the informativeness of morphological characters showed that sperm ultrastructure characters are among the best morphological features to diagnose bivalve clades, followed by characters of the shell, including its microstructure. Our study found support for monophyly of most broadly recognised higher bivalve taxa, although support was not uniform for Protobranchia. However, monophyly of the bivalves with protobranchiate gills was the best-supported hypothesis with incremental morphological and/or molecular sequence data. Autobranchia, Pteriomorphia, Heteroconchia, Palaeoheterodonta, Archiheterodonta, Euheterodonta, Anomalodesmata and Imparidentia new clade ( = Euheterodonta excluding Anomalodesmata) were recovered across analyses, irrespective of data treatment or analytical framework. Another clade supported by our analyses but not formally recognised in the literature includes Palaeoheterodonta and Archiheterodonta, which emerged under multiple analytical conditions. The origin and diversification of each of these major clades is Cambrian or Ordovician, except for Archiheterodonta, which diverged from Palaeoheterodonta during the Cambrian, but diversified during the Mesozoic. Although the radiation of some lineages was shifted towards the Palaeozoic (Pteriomorphia, Anomalodesmata), or presented a gap between origin and diversification (Archiheterodonta, Unionida), Imparidentia showed steady diversification through the Palaeozoic and Mesozoic. Finally, a classification system with six major monophyletic lineages is proposed to comprise modern Bivalvia: Protobranchia, Pteriomorphia, Palaeoheterodonta, Archiheterodonta, Anomalodesmata and Imparidentia

    Effect of multi-planar CT image reformatting on surgeon diagnostic performance for localizing thoracolumbar disc extrusions in dogs

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    Accurate pre-operative localization and removal of disc material are important for minimizing morbidity in dogs with thoracolumbar disc extrusions. Computed tomography (CT) is an established technique for localizing disc extrusions in dogs, however the effect of multi-planar reformatting (MPR) on surgeon diagnostic performance has not been previously described. The purpose of this study was to test the effect of MPR CT on surgeon diagnostic accuracy, certainty and agreement for localizing thoracolumbar disc extrusions in dogs. Two veterinary surgeons and one veterinary neurologist who were unaware of surgical findings independently reviewed randomized sets of two-dimensional (2D) and MPR CT images from 111 dogs with confirmed thoracolumbar disc extrusions. For each set of images, readers recorded their localizations for extruded disc material and their diagnostic certainty. For MPR images, readers also recorded views they considered most helpful. Diagnostic accuracy estimates, mean diagnostic certainty scores and inter-observer agreement were compared using surgery as the gold standard. Frequencies were compared for MPR views rated most helpful. Diagnostic accuracy estimates were significantly greater for MPR vs. 2D CT images in one reader. Mean diagnostic certainty scores were significantly greater for MPR images in two readers. The change in agreement between 2D and MPR images differed from zero for all analyses (site, side, number affected) among all three readers. Multi-planar views rated most helpful with the highest frequency were oblique transverse and curved dorsal planar MPR views. Findings from this study indicate that multi-planar CT can improve surgeon diagnostic performance for localizing canine thoracolumbar disc extrusions
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