423 research outputs found

    VBLAST Detection Algorithms Utilizing Soft Symbol Estimate and Noncircular CAI

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    Load transient between conventional diesel operation and low-temperature combustion

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    The operation of diesel low-temperature combustion engines is currently limited to low-load and medium-load conditions. Mode transitions between diesel low-temperature combustion and conventional diesel operation and between conventional diesel operation and diesel low-temperature combustion are therefore necessary to meet typical legislated driving-cycle load requirements, e.g. those of the New European Driving Cycle. Owing to the markedly different response timescales of the engine’s turbocharger, exhaust gas recirculation and fuelling systems, these combustion mode transitions are typically characterised by increased pollutant emissions. In the present paper, the transition from conventional diesel operation to diesel low-temperature combustion in a decreasing-load transient is considered. The results of an experimental study on a 0.51 l single-cylinder high-speed diesel engine are reported in a series of steady-state ‘pseudo-transient’ operating conditions, each pseudo-transient test point being representative of an individual cycle condition from within a mode transition as predicted by the combination of real-world transient test data (for fuelling and load) and one-dimensional transient simulations (for intake manifold pressure and exhaust gas recirculation rate). These test conditions are then established on the engine using independently controllable exhaust gas recirculation and boost systems. The results show for the first time that the intermediate cycle conditions encountered during combustion mode change driven by the load transient pose a significant operating challenge, particularly with respect to control of carbon monoxide, total hydrocarbon and smoke emissions. A split-fuel-injection strategy is found to be effective in mitigating the negative effects of the mode change on smoke emissions without significantly increasing oxides of nitrogen or decreasing fuel economy; however, unburned hydrocarbon emissions are increased. Additional experimental testing was also conducted at selected intermediate cycles to understand the sensitivity of key fuel injection parameters with the split-injection strategy on engine performance and emissions

    Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

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    Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

    An unusual feruloyl esterase belonging to family VIII esterases and displaying a broad substrate range

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    A thermophilic compost metagenomic library constructed in Escherichia coli was functionally screenedfor novel esterases. Of the 110,592 fosmid clones screened, 25 clones demonstrated degradative activ-ity on glyceryl tributyrate (a hit rate of 1:4,423). Four clones displayed ferulic acid esterase activityand were sequenced using 454 Titanium sequencing technology. EstG34, a 410 amino acid protein, wasidentified as having high sequence identity with a number of bacterial -lactamases. EstG34 has theS-X-X-K motif which is conserved in class C -lactamases and family VIII carboxylesterases. Purifiedrecombinant EstG34 had a molecular mass of 42 kDa and displayed hydrolytic activity towards a vari-ety of p-nitrophenyl esters, hydroxycinnamic acid esters and -naphthol acetate. EstG34 represents thefirst family VIII carboxylesterase and -lactamase fold enzyme, able to hydrolyse ferulate and a numberof other hydroxycinnamic acid esters. In addition, EstG34 is the first reported FAE to not adopt the / hydrolase conformation. The sequence similarity and wide substrate utilization capability of this esterasecomplicates its placement within current classification systems, but also draws attention to the enzyme’spotential versatility.The National Research Foundation (NRF) and the Technology Innovation Agency (TIA), South Africa(Project number PB99/08).http://www.elsevier.com/locate/molcatb2016-08-31hb201

    Provider and female client economic costs of integrated sexual and reproductive health and HIV Services in Zimbabwe

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    A retrospective facility-based costing study was undertaken to estimate the comparative cost per visit of five integrated sexual and reproductive health and HIV (human immuno-deficiency virus) services (provider perspective) within five clinic sites. These five clinics were part of four service delivery models: Non-governmental-organisation (NGO) directly managed model (Chitungwiza and New Africa House sites), NGO partner managed site (Mutare site), private-public-partnership (PPP) model (Chitungwiza Profam Clinic), and NGO directly managed outreach (operating from New Africa House site. In addition client cost exit interviews (client perspective) were conducted among 856 female clients exiting integrated services at three of the sites. Our costing approach involved first a facility bottom-up costing exercise (February to April 2015), conducted to quantify and value each resource input required to provide individual SRH and HIV services. Secondly overhead financial expenditures were allocated top-down from central office to sites and then respective integrated service based on pre-defined allocation factors derived from both the site facility observations and programme data for the prior 12 months. Costs were assessed in 2015 United States dollars (USD). Costs were assessed for HIV testing and counselling, screening and treatment of sexually transmitted infections, tuberculosis screening with smear microscopy, family planning, and cervical cancer screening and treatment employing visual inspection with acetic acid and cervicography and cryotherapy. Variability in costs per visit was evident across the models being highest for cervical cancer screening and cryotherapy (range: US6.98US6.98 - US49.66). HIV testing and counselling showed least variability (range; US10.96US10.96 - US16.28). In general the PPP model offered integrated services at the lowest unit costs whereas the partner managed site was highest. Significant client costs remain despite availability of integrated sexual and reproductive health and HIV services free of charge in our Zimbabwe study setting. Situating services closer to communities, incentives, transport reimbursements, reducing waiting times and co-location of sexual and reproductive health and HIV services may help minimise impact of client costs

    Laser produced electromagnetic pulses : Generation, detection and mitigation

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    This paper provides an up-to-date review of the problems related to the generation, detection and mitigation of strong electromagnetic pulses created in the interaction of high-power, high-energy laser pulses with different types of solid targets. It includes new experimental data obtained independently at several international laboratories. The mechanisms of electromagnetic field generation are analyzed and considered as a function of the intensity and the spectral range of emissions they produce. The major emphasis is put on the gHz frequency domain, which is the most damaging for electronics and may have important applications. The physics of electromagnetic emissions in other spectral domains, in particular THz and MHz, is also discussed. The theoretical models and numerical simulations are compared with the results of experimental measurements, with special attention to the methodology of measurements and complementary diagnostics. Understanding the underlying physical processes is the basis for developing techniques to mitigate the electromagnetic threat and to harness electromagnetic emissions, which may have promising applications

    The Emergence of Miller's Magic Number on a Sparse Distributed Memory

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    Human memory is limited in the number of items held in one's mind—a limit known as “Miller's magic number”. We study the emergence of such limits as a result of the statistics of large bitvectors used to represent items in memory, given two postulates: i) the Sparse Distributed Memory; and ii) chunking through averaging. Potential implications for theoretical neuroscience are discussed

    The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

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    This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

    In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington's disease subjects

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    Huntington's disease (HD) is a neurodegenerative disorder previously thought to be of primary neuronal origin, despite ubiquitous expression of mutant huntingtin (mHtt). We tested the hypothesis that mHtt expressed in astrocytes may contribute to the pathogenesis of HD. To better understand the contribution of astrocytes in HD in vivo, we developed a novel mouse model using lentiviral vectors that results in selective expression of mHtt into striatal astrocytes. Astrocytes expressing mHtt developed a progressive phenotype of reactive astrocytes that was characterized by a marked decreased expression of both glutamate transporters, GLAST and GLT-1, and of glutamate uptake. These effects were associated with neuronal dysfunction, as observed by a reduction in DARPP-32 and NR2B expression. Parallel studies in brain samples from HD subjects revealed early glial fibrillary acidic protein expression in striatal astrocytes from Grade 0 HD cases. Astrogliosis was associated with morphological changes that increased with severity of disease, from Grades 0 through 4 and was more prominent in the putamen. Combined immunofluorescence showed co-localization of mHtt in astrocytes in all striatal HD specimens, inclusive of Grade 0 HD. Consistent with the findings from experimental mice, there was a significant grade-dependent decrease in striatal GLT-1 expression from HD subjects. These findings suggest that the presence of mHtt in astrocytes alters glial glutamate transport capacity early in the disease process and may contribute to HD pathogenesis
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