272 research outputs found

    Unconditionally convergent time domain adaptive and time-frequency techniques for epicyclic gearbox vibration

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    Condition monitoring of epicyclic gearboxes through vibration signature analysis, with particular focus on time domain methods and the use of adaptive filtering techniques for the purpose of signal enhancement, is the central theme of this work. Time domain filtering methods for the purpose of removal of random noise components from periodic, but not necessarily stationary or cyclostationary, signals are developed. Damage identification is accomplished through vibration signature analysis by nonstationary timefrequency methods, belonging to Cohen’s general class of time-frequency distributions, strictly based in the time domain. Although a powerful and commonly used noise reduction technique, synchronous averaging requires alternate sensors in addition to the vibration pickup. For this reason the use of time domain techniques that employ only the vibration data is investigated. Adaptive filters may be used to remove random noise from the nonstationary signals considered. The well-known Least Mean Squares algorithm is employed in an adaptive line enhancer configuration. To counter the much discussed convergence difficulties that are often experienced when the least mean squares algorithm is applied, a new unconditionally convergent algorithm based on the spherical quadratic steepest descent method is presented. The spherical quadratic steepest descent method has been shown to be unconditionally convergent when applied to a quadratic objective function. Time-frequency methods are succinctly employed to analyse the vibration signals simultaneously in the time and frequency domains. Transients covering a wide frequency range are a clear and definite indication of impacting events as gear teeth mate, and observation of such events on a timefrequency distribution are used to indicate damage to the transmission. The pseudo Wigner-Ville distribution and the Spectrogram, both belonging to Cohen’s general class of time-frequency distributions are comparatively used to the end of damage identification. It is shown that an unconditionally convergent adaptive filtering technique used in conjunction with time-frequency methods can indicate a damaged condition in an epicyclic gearbox, where the non-adaptively filtered data did not present clear indications of damage.Dissertation (MEng (Mechanical Engineering))--University of Pretoria, 2007.Mechanical and Aeronautical EngineeringMEngMEngunrestricte

    Hypotheses for the Origin of the Hypanis Fan-Shaped Deposit at the Edge of the Chryse Escarpment, Mars: Is it a Delta?

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    We investigated the origin of the fan-shaped deposit at the end of Hypanis Valles that has previously been proposed as an ExoMars, Mars 2020, and human mission candidate landing site, and found evidence that the landform is an ancient delta. Previous work suggests that the deposit originated from a time of fluvial activity both distinct from and prior to catastrophic outflow, and crater counting placed the deposit’s age at  ≄ 3.6 Ga. We found over 30 thin sedimentary strata in the proposed delta wall, and from our slope analysis conclude that the fluvial sequence is consistent with a lowering/retreating shoreline. We measured nearly horizontal bedding dip angles ranging from 0° to 2° over long stretches of cliff and bench exposures seen in HiRISE images and HiRISE stereo DTMs. From THEMIS night IR images we determined that the fan-shaped deposit has a low thermal inertia (150-240 Jm-2 K-1 s-1/2) and the surrounding darker-toned units correspond to thermal inertia values as high as 270-390 Jm-2 K-1 s-1/2. We interpret these findings to indicate that the fan-shaped deposit consists mostly of silt-sized and possibly finer grains, and that the extremely low grade and large lateral extent of these beds implies that the depositional environment was calm and relatively long-lived. We interpret the geomorphology and composition as incompatible with an alluvial fan or mudflow hypothesis. From our stratigraphic mapping we interpret the order of events which shaped the region. After the Chryse impact, sediment filled the basin, a confined lake or sea formed allowing a large delta to be deposited near its shoreline, the water level receded to the north, darker sedimentary/volcanic units covered the region and capped the light-toned deposit as hydro-volcanic eruptions shaped the interior of Lederberg crater, freeze/thaw cycles and desiccation induced local fracturing, and finally wrinkle ridges associated with rounded cones warped the landscape following trends in degraded crater rims and existing tectonic features. The ancient deltaic deposit we observe today was largely untouched by subsequent catastrophic outflows, and its surface has been only moderately reshaped by over 3 billion years of aeolian erosion

    Cytokine and Protein Markers of Leprosy Reactions in Skin and Nerves: Baseline Results for the North Indian INFIR Cohort

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    Leprosy affects skin and peripheral nerves. Although we have effective antibiotics to treat the mycobacterial infection, a key part of the disease process is the accompanying inflammation. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called ‘reactions’. These reactions are associated with worsening of the nerve damage. We recruited a cohort of 303 newly diagnosed leprosy patients in North India with the aim of understanding and defining the pathological processes better. We took skin and nerve biopsies from patients and examined them to define which molecules and mediators of inflammation were present. We found high levels of the cytokines Tumour Necrosis Factor alpha, Transforming Growth Factor beta and inducible Nitric Oxide Synthase in biopsies from patients with reactions. We also found high levels of bacteria and inflammation in the nerves. These experiments tell us that we need to determine which other molecules are present and to explore ways of switching off the production of these pro-inflammatory molecules

    Involvement of Raft Aggregates Enriched in Fas/CD95 Death-Inducing Signaling Complex in the Antileukemic Action of Edelfosine in Jurkat Cells

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    BACKGROUND: Recent evidence suggests that co-clustering of Fas/CD95 death receptor and lipid rafts plays a major role in death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: By a combination of genetic, biochemical, and ultrastructural approaches, we provide here compelling evidence for the involvement of lipid raft aggregates containing recruited Fas/CD95 death receptor, Fas-associated death domain-containing protein (FADD), and procaspase-8 in the induction of apoptosis in human T-cell leukemia Jurkat cells by the antitumor drug edelfosine, the prototype compound of a promising family of synthetic antitumor lipids named as synthetic alkyl-lysophospholipid analogues. Co-immunoprecipitation assays revealed that edelfosine induced the generation of the so-called death-inducing signaling complex (DISC), made up of Fas/CD95, FADD, and procaspase-8, in lipid rafts. Electron microscopy analyses allowed to visualize the formation of raft clusters and their co-localization with DISC components Fas/CD95, FADD, and procaspase-8 following edelfosine treatment of Jurkat cells. Silencing of Fas/CD95 by RNA interference, transfection with a FADD dominant-negative mutant that blocks Fas/CD95 signaling, and specific inhibition of caspase-8 prevented the apoptotic response triggered by edelfosine, hence demonstrating the functional role of DISC in drug-induced apoptosis. By using radioactive labeled edelfosine and a fluorescent analogue, we found that edelfosine accumulated in lipid rafts, forming edelfosine-rich membrane raft clusters in Jurkat leukemic T-cells. Disruption of these membrane raft domains abrogated drug uptake and drug-induced DISC assembly and apoptosis. Thus, edelfosine uptake into lipid rafts was critical for the onset of both co-aggregation of DISC in membrane rafts and subsequent apoptotic cell death. CONCLUSIONS/SIGNIFICANCE: This work shows the involvement of DISC clusters in lipid raft aggregates as a supramolecular and physical entity responsible for the induction of apoptosis in leukemic cells by the antitumor drug edelfosine. Our data set a novel framework and paradigm in leukemia therapy, as well as in death receptor-mediated apoptosis

    Study protocol for the translating research in elder care (TREC): building context – an organizational monitoring program in long-term care project (project one)

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    <p>Abstract</p> <p>Background</p> <p>While there is a growing awareness of the importance of organizational context (or the work environment/setting) to successful knowledge translation, and successful knowledge translation to better patient, provider (staff), and system outcomes, little empirical evidence supports these assumptions. Further, little is known about the factors that enhance knowledge translation and better outcomes in residential long-term care facilities, where care has been shown to be suboptimal. The project described in this protocol is one of the two main projects of the larger five-year Translating Research in Elder Care (TREC) program.</p> <p>Aims</p> <p>The purpose of this project is to establish the magnitude of the effect of organizational context on knowledge translation, and subsequently on resident, staff (unregulated, regulated, and managerial) and system outcomes in long-term care facilities in the three Canadian Prairie Provinces (Alberta, Saskatchewan, Manitoba).</p> <p>Methods/Design</p> <p>This study protocol describes the details of a multi-level – including provinces, regions, facilities, units within facilities, and individuals who receive care (residents) or work (staff) in facilities – and longitudinal (five-year) research project. A stratified random sample of 36 residential long-term care facilities (30 urban and 6 rural) from the Canadian Prairie Provinces will comprise the sample. Caregivers and care managers within these facilities will be asked to complete the TREC survey – a suite of survey instruments designed to assess organizational context and related factors hypothesized to be important to successful knowledge translation and to achieving better resident, staff, and system outcomes. Facility and unit level data will be collected using standardized data collection forms, and resident outcomes using the Resident Assessment Instrument-Minimum Data Set version 2.0 instrument. A variety of analytic techniques will be employed including descriptive analyses, psychometric analyses, multi-level modeling, and mixed-method analyses.</p> <p>Discussion</p> <p>Three key challenging areas associated with conducting this project are discussed: sampling, participant recruitment, and sample retention; survey administration (with unregulated caregivers); and the provision of a stable set of study definitions to guide the project.</p

    Quintom Cosmology: Theoretical implications and observations

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    We review the paradigm of quintom cosmology. This scenario is motivated by the observational indications that the equation of state of dark energy across the cosmological constant boundary is mildly favored, although the data are still far from being conclusive. As a theoretical setup we introduce a no-go theorem existing in quintom cosmology, and based on it we discuss the conditions for the equation of state of dark energy realizing the quintom scenario. The simplest quintom model can be achieved by introducing two scalar fields with one being quintessence and the other phantom. Based on the double-field quintom model we perform a detailed analysis of dark energy perturbations and we discuss their effects on current observations. This type of scenarios usually suffer from a manifest problem due to the existence of a ghost degree of freedom, and thus we review various alternative realizations of the quintom paradigm. The developments in particle physics and string theory provide potential clues indicating that a quintom scenario may be obtained from scalar systems with higher derivative terms, as well as from non-scalar systems. Additionally, we construct a quintom realization in the framework of braneworld cosmology, where the cosmic acceleration and the phantom divide crossing result from the combined effects of the field evolution on the brane and the competition between four and five dimensional gravity. Finally, we study the outsets and fates of a universe in quintom cosmology. In a scenario with null energy condition violation one may obtain a bouncing solution at early times and therefore avoid the Big Bang singularity. Furthermore, if this occurs periodically, we obtain a realization of an oscillating universe. Lastly, we comment on several open issues in quintom cosmology and their connection to future investigations.Comment: 105 pages, 36 figures, version published at Physics Report

    A guide to writing systematic reviews of rare disease treatments to generate FAIR-compliant datasets: building a Treatabolome

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    Abstract: Background: Rare diseases are individually rare but globally affect around 6% of the population, and in over 70% of cases are genetically determined. Their rarity translates into a delayed diagnosis, with 25% of patients waiting 5 to 30 years for one. It is essential to raise awareness of patients and clinicians of existing gene and variant-specific therapeutics at the time of diagnosis to avoid that treatment delays add up to the diagnostic odyssey of rare diseases’ patients and their families. Aims: This paper aims to provide guidance and give detailed instructions on how to write homogeneous systematic reviews of rare diseases’ treatments in a manner that allows the capture of the results in a computer-accessible form. The published results need to comply with the FAIR guiding principles for scientific data management and stewardship to facilitate the extraction of datasets that are easily transposable into machine-actionable information. The ultimate purpose is the creation of a database of rare disease treatments (“Treatabolome”) at gene and variant levels as part of the H2020 research project Solve-RD. Results: Each systematic review follows a written protocol to address one or more rare diseases in which the authors are experts. The bibliographic search strategy requires detailed documentation to allow its replication. Data capture forms should be built to facilitate the filling of a data capture spreadsheet and to record the application of the inclusion and exclusion criteria to each search result. A PRISMA flowchart is required to provide an overview of the processes of search and selection of papers. A separate table condenses the data collected during the Systematic Review, appraised according to their level of evidence. Conclusions: This paper provides a template that includes the instructions for writing FAIR-compliant systematic reviews of rare diseases’ treatments that enables the assembly of a Treatabolome database that complement existing diagnostic and management support tools with treatment awareness data
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