328 research outputs found

    Surface cleaning technologies for the removal of crosslinked epoxide resin

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    This study provides details of the use of laser ablation and sodium hydride cleaning processes for the removal of crosslinked epoxide and other residues from resin transfer moulding (RTM) tool substrates, as used in the aerospace industry. The requirement for removal of such contamination is so that the mould can be re-used, following the subsequent application of an external release agent. These tools are, typically, fabricated from steel, nickel or CFRP composite materials; this paper focuses on the use of nickel substrates. The requirement to clean large surface areas quickly to satisfy commercial restraints, compromises the degree of absolute cleanliness that can be obtained. However, in applications where cleaning time is not a constraint, laser cleaning can be a very gentle and efficient process; typically Nd:YAG lasers find application in this area. In contrast, high power lasers are desirable for industrial scale applications where large areas need to be cleaned quickly. In this instance pulsed CO2 lasers can be used. The use of sodium hydride was also found to be highly successful in removing crosslinked organic contamination providing that suitable hard rinse and drying operations were also carried out

    A review and comparative study of release coatings for optimised abhesion in resin transfer moulding applications

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    In this study, a number of abhesion promoting coatings were considered in terms of their physicochemical and release properties. The techniques used to further this study include; FEGSEM, AFM, profilometry, AFM, XPS, AES, SSIMS, FTIR and contact angle analysis for coating physical and chemical characterisation along with PF-AFM and other adhesion and mechanical tests to determine surface release properties. These coatings were applied to metal substrates and were based upon silicone, fluoropolymer or metal-PTFE composite chemistry, all being potentially useful as release films for resin transfer moulding (RTM) applications. The semi-permanent Frekote B15/710 NC mould release coating system, which is based on PDMS, proved extremely effective in terms of release against a cured epoxide applied under pressure. Although fluoroalkylsilane coatings offer a number of technological advantages for release applications they generally produce very thin coatings which conform any existing surface topography and adhesion through mechanical interlocking occurs. The commercial PTFE-based coatings were found to provide poor release properties due to the presence of surface microcracks which allowed epoxide penetration when cured under elevated pressure and temperature. Electroless Ni/PTFE composite coatings comprise hard nickel-phosphorus matrix containing a very fine dispersion of PTFE particles. The matrix proved sufficiently robust for industrial applications and the low friction and surface energy provided by the embedded PTFE combined with macroscopic scale surface roughness provided efficient mould release

    Notes on the ecology of Ethiopian Bush-crow Zavattariornis stresemanni

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    We used the focal sampling method to conduct a behavioural study of the endemic Ethiopian Bush-crow Zavattariornis stresemanni in the Yabelo-Mega area of southern Ethiopia. We found that feeding rates were lower in areas with low sward height and low numbers of trees. This was particularly concerning given the degradation of natural habitat in this area

    3D Growth of Cancer Cells Elicits Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers

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    Tumor cells exhibit altered lipid metabolism compared with normal cells. Cell signaling kinases are important for regulating lipid synthesis and energy storage. How upstream kinases regulate lipid content, versus direct targeting of lipid-metabolizing enzymes, is currently unexplored. We evaluated intracellular lipid concentrations in prostate and breast tumor spheroids, treated with drugs directly inhibiting metabolic enzymes fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), diacylglyceride acyltransferase (DGAT), and pyruvate dehydrogenase kinase (PDHK), or cell signaling kinase enzymes PI3K, AKT, and mTOR with lipidomic analysis. We assessed whether baseline lipid profiles corresponded to inhibitors' effectiveness in modulating lipid profiles in three-dimensional (3D) growth and their relationship to therapeutic activity. Inhibitors against PI3K, AKT, and mTOR significantly inhibited MDA-MB-468 and PC3 cell growth in two-dimensional (2D) and 3D spheroid growth, while moderately altering lipid content. Conversely, metabolism inhibitors against FASN and DGAT altered lipid content most effectively, while only moderately inhibiting growth compared with kinase inhibitors. The FASN and ACC inhibitors' effectiveness in MDA-MB-468, versus PC3, suggested the former depended more on synthesis, whereas the latter may salvage lipids. Although baseline lipid profiles did not predict growth effects, lipid changes on therapy matched the growth effects of FASN and DGAT inhibitors. Several phospholipids, including phosphatidylcholine, were also upregulated following treatment, possibly via the Kennedy pathway. As this promotes tumor growth, combination studies should include drugs targeting it. Two-dimensional drug screening may miss important metabolism inhibitors or underestimate their potency. Clinical studies should consider serial measurements of tumor lipids to prove target modulation. Pretherapy tumor classification by de novo lipid synthesis versus uptake may help demonstrate efficacy

    Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress

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    A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment

    Belle II Technical Design Report

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    The Belle detector at the KEKB electron-positron collider has collected almost 1 billion Y(4S) events in its decade of operation. Super-KEKB, an upgrade of KEKB is under construction, to increase the luminosity by two orders of magnitude during a three-year shutdown, with an ultimate goal of 8E35 /cm^2 /s luminosity. To exploit the increased luminosity, an upgrade of the Belle detector has been proposed. A new international collaboration Belle-II, is being formed. The Technical Design Report presents physics motivation, basic methods of the accelerator upgrade, as well as key improvements of the detector.Comment: Edited by: Z. Dole\v{z}al and S. Un

    Open letter from UK based academic scientists to the secretaries of state for digital, culture, media and sport and for health and social care regarding the need for independent funding for the prevention and treatment of gambling harms

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    First paragraph: Dear secretaries of state, As leading academic scientists studying gambling behaviours and its harms, we are writing to express our concern about the continuing support shown for the voluntary system of funding treatment, prevention and research in Great Britain. We feel compelled to write to you following the Betting and Gaming Council’s (BGC) recent announcement (17 June 2020) that five of its operators will now allocate the long awaited increase in funding for prevention and treatment, first promised on 2 August 2019, to GambleAware rather than the charity Action Against Gambling Harms. Irrespective of which organisation funds are given to, the BGC’s announcement exemplifies the longstanding weakness of a funding system that allows the gambling industry to regulate the availability and distribution of vital funds to address gambling harms across our communities. As we outline below, the continuance of this arrangement produces several negative effects that undermine the collective effort to reduce harms from gambling. It is also our belief that funds for research into gambling harms and their reduction should primarily be distributed through recognised independent organisations, such as UK Research and Innovation. We hereby urge you, as the secretaries of state with responsibilities for addressing gambling harms, to implement a statutory levy to fund effective prevention and treatment of gambling harms that is free both from industry influence and the perception of industry influence...... [Read more in the article]Additional co-authors: Carolyn Downs, Simon Dymond, Emanuele Fino, Elizabeth Goyder, Cindy Gray, Mark Griffiths, Peter Grindrod, Lee Hogan, Alice Hoon, Richard James, Bev John, Jill Manthorpe, Jim McCambridge, David McDaid, Martin McKee, Sally McManus, Antony Moss, Caroline Norrie, David J Nutt, Jim Orford, Rob Pryce, Gerda Reith, Amanda Roberts, Emmett Roberts, Gareth Roderique-Davies, Jim Rogers, Robert D Rogers, Stephen Sharman, John Strang, Richard Tunney, John Turner, Robert West, David Zendl

    Adrenalectomy-Produced Facilitation of Pavlovian Conditioned Cardiodecelerations in Immobilized Rats

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    Previous evidence has suggested that both hormonal and behavioral aspects of adrenal stress activation may contribute to heart rate (HR) conditioning during physical/pharmacological immobilization. Accordingly, four studies were conducted to determine if bilateral adrenalectomy facilitates stimulus-control over Pavlovian conditioned cardiodecelerations in rats immobilized either through physical restraint or neuromuscular paralysis. Plasma corticosterone assays were used as an index of the effectiveness of adrenal removal. The results showed that adrenalectomy facilitated both simple and discriminated Pavlovian conditioned cardiodecelerations in rats paralyzed with d-tubocurarine chloride (dTC) without significantly altering the characteristics of EMG recovery from paralysis. Similarly, adrenalectomy facilitated simple Pavlovian HR conditioning in physically restrained rats. The results suggest that adrenal activation may disrupt the parasympathetically-mediated Pavlovian conditioned cardiodeceleration in the physically-and dTC-immobilized rat. However, the specific nature of neuroendocrine mechanisms underlying cardiovascular conditioning during immobilization remains problematical.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75069/1/j.1469-8986.1977.tb03371.x.pd

    A Novel Mechanism of Programmed Cell Death in Bacteria by Toxin–Antitoxin Systems Corrupts Peptidoglycan Synthesis

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    Most genomes of bacteria contain toxin–antitoxin (TA) systems. These gene systems encode a toxic protein and its cognate antitoxin. Upon antitoxin degradation, the toxin induces cell stasis or death. TA systems have been linked with numerous functions, including growth modulation, genome maintenance, and stress response. Members of the epsilon/zeta TA family are found throughout the genomes of pathogenic bacteria and were shown not only to stabilize resistance plasmids but also to promote virulence. The broad distribution of epsilon/zeta systems implies that zeta toxins utilize a ubiquitous bacteriotoxic mechanism. However, whereas all other TA families known to date poison macromolecules involved in translation or replication, the target of zeta toxins remained inscrutable. We used in vivo techniques such as microscropy and permeability assays to show that pneumococcal zeta toxin PezT impairs cell wall synthesis and triggers autolysis in Escherichia coli. Subsequently, we demonstrated in vitro that zeta toxins in general phosphorylate the ubiquitous peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG) and that this activity is counteracted by binding of antitoxin. After identification of the product we verified the kinase activity in vivo by analyzing metabolite extracts of cells poisoned by PezT using high pressure liquid chromatograpy (HPLC). We further show that phosphorylated UNAG inhibitis MurA, the enzyme catalyzing the initial step in bacterial peptidoglycan biosynthesis. Additionally, we provide what is to our knowledge the first crystal structure of a zeta toxin bound to its substrate. We show that zeta toxins are novel kinases that poison bacteria through global inhibition of peptidoglycan synthesis. This provides a fundamental understanding of how epsilon/zeta TA systems stabilize mobile genetic elements. Additionally, our results imply a mechanism that connects activity of zeta toxin PezT to virulence of pneumococcal infections. Finally, we discuss how phosphorylated UNAG likely poisons additional pathways of bacterial cell wall synthesis, making it an attractive lead compound for development of new antibiotics
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