13 research outputs found

    Tensile Properties and Microstructure of Inconel 718 Fabricated with Electron Beam Freeform Fabrication (EBF(sup 3))

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    Electron beam freeform fabrication (EBF3) direct metal deposition processing was used to fabricate two Inconel 718 single-bead-width wall builds and one multiple-bead-width block build. Specimens were machined to evaluate microstructure and room temperature tensile properties. The tensile strength and yield strength of the as-deposited material from the wall and block builds were greater than those for conventional Inconel 718 castings but were less than those for conventional cold-rolled sheet. Ductility levels for the EBF3 material were similar to those for conventionally-processed sheet and castings. An unexpected result was that the modulus of the EBF3-deposited Inconel 718 was significantly lower than that of the conventional material. This low modulus may be associated with a preferred crystallographic orientation resultant from the deposition and rapid solidification process. A heat treatment with a high solution treatment temperature resulted in a recrystallized microstructure and an increased modulus. However, the modulus was not increased to the level that is expected for Inconel 718

    Impact of Pulsed Electric Field Treatment on Barley Germination for Malting

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    The malting process takes one week to steep, germinate, and kiln barley to make malt. Making quality malt is critically important to achieve the desired attributes of the finished beer, and the process is time-intensive and costly. Malt quality is assessed by indicators including β-glucan quantity, α-amylase activity, Free Amino Nitrogen (FAN) content, and overall extract concentration in the finished malt. Here, we report Pulsed Electric Field (PEF) treatment of barley to accelerate malt production. A small-scale trial of 250 g to 1.00 kg barley, was evaluated for germination at two PEF treatment conditions, generically referred to as “low” and “high”, that resulted in increased barley rootlet length during germination of 1.3 mm longer than was observed for the control. Large-scale trials of 1.00 kg–3.00 kg barley, resulted in an increase in germination rate and a decrease of β-glucan concentration in the PEF treated barley. Micromalted barley using PEF parameters of 1.0 kV/cm and 15.0 kJ/kg displayed a reduction in β-glucan concentration by 38%, and increase in malt extract by 1.5%, FAN by 6.2%, and α-amylase by 8.4%, supporting the hypothesis that PEF treated barley generates more and better malt, leading to greater efficiency in the beer making process

    Host Gene Expression Profiling of Dengue Virus Infection in Cell Lines and Patients

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    Dengue is the most prevalent mosquito-born viral disease affecting humans, yet there is, at present, no drug treatment for the disease nor are there any validated host targets for therapeutic intervention. Using microarray technology to monitor the response of virtually every human gene, we aimed to identify the ways in which humans interact with dengue virus during infection in order to discover new therapeutic targets that could be exploited to control viral replication. From the activated genes, we identified three pathways common to in vitro and in vivo infection; the NF-κB initiated immune pathway, the type I interferon pathway, and the ubiquitin proteasome pathway. We next found that inhibiting the ubiquitin proteasome pathway, or activating the type I interferon pathway, resulted in significant inhibition of viral replication. However, inhibiting the NF-κB initiated immune pathway had no effect on viral replication. We suggest that drugs that target the ubiquitin proteasome pathway may prove effective at killing the dengue virus, and, if used therapeutically, improve clinical outcome in dengue disease

    Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

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    BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

    Genomic investigations of unexplained acute hepatitis in children

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    Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

    A genomics approach to understanding host response during dengue infection.

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    Dengue infection results in a wide clinical spectrum, ranging from asymptomatic, through fever (DF), to the life threatening complications haemorrhagic fever (DHF) and shock syndrome (DSS). Although we now understand that factors such as repeat infections and the type or magnitude of the host response are important in determining severity, the mechanisms of these actions remain largely unknown. Understanding this host-pathogen interaction may enable outcome prediction and new therapy options. Developments in biology now allow a 'systems approach' to be applied to this problem, utilizing whole genomes of both human and virus, in vitro and in vivo to enable a more complete picture of their interplay to be built up. We have developed a chip-based approach to viral sequencing, to increase efficiency and enable large numbers ofgenomes to be completed, together with a web-based interpretation tool. We have also applied human whole genome expression arrays (24000 genes) to characterize the types of host response made to infection and plan to investigate the role of host variation using human whole genome genetic association studies in the future. These technologies have identified novel host pathways involved in viral replication in vitro, and also host immune responses, such as the interferon signalling pathway, that are influenced by viral sequence. This data will be further refined through interlinking with similar data obtained from a large study of dengue patients, initiated in Singapore, that is able to look at the early host response to infection

    Redesigning photosynthesis to sustainably meet global food and bioenergy demand

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    The world’s crop productivity is stagnating whereas population growth, rising affluence, and mandates for biofuels put increasing demands on agriculture. Meanwhile, demand for increasing cropland competes with equally crucial global sustainability and environmental protection needs. Addressing this looming agricultural crisis will be one of our greatest scientific challenges in the coming decades, and success will require substantial improvements at many levels. We assert that increasing the efficiency and productivity of photosynthesis in crop plants will be essential if this grand challenge is to be met. Here, we explore an array of prospective redesigns of plant systems at various scales, all aimed at increasing crop yields through improved photosynthetic efficiency and performance. Prospects range from straightforward alterations, already supported by preliminary evidence of feasibility, to substantial redesigns that are currently only conceptual, but that may be enabled by new developments in synthetic biology. Although some proposed redesigns are certain to face obstacles that will require alternate routes, the efforts should lead to new discoveries and technical advances with important impacts on the global problem of crop productivity and bioenergy production.This article is published as Ort, Donald R., Sabeeha S. Merchant, Jean Alric, Alice Barkan, Robert E. Blankenship, Ralph Bock, Roberta Croce et al. "Redesigning photosynthesis to sustainably meet global food and bioenergy demand." Proceedings of the national academy of sciences 112, no. 28 (2015): 8529-8536. 10.1073/pnas.1424031112. Posted with permission.</p
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