1,730 research outputs found

    On the determination of functional requirements in a maintenance environment

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    Dissecting the genetic components of a quantitative trait locus for blood pressure and renal pathology on rat chromosome 3

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    Background: We have previously confirmed the importance of rat chromosome 3 (RNO3) genetic loci on blood pressure elevation, pulse pressure (PP) variability and renal pathology during salt challenge in the stroke-prone spontaneously hypertensive (SHRSP) rat. The aims of this study were to generate a panel of RNO3 congenic sub-strains to genetically dissect the implicated loci and identify positional candidate genes by microarray expression profiling and analysis of next-generation sequencing data. Method and results: A panel of congenic sub-strains were generated containing Wistar-Kyoto (WKY)-introgressed segments of varying size on the SHRSP genetic background, focused within the first 50 Mbp of RNO3. Haemodynamic profiling during salt challenge demonstrated significantly reduced systolic blood pressure, diastolic blood pressure and PP variability in SP.WKYGla3a, SP.WKYGla3c, SP.WKYGla3d and SP.WKYGla3e sub-strains. Only SBP and DBP were significantly reduced during salt challenge in SP.WKYGla3b and SP.WKYGla3f sub-strains, whereas SP.WKYGla3g rats did not differ in haemodynamic response to SHRSP. Those sub-strains demonstrating significantly reduced PP variability during salt challenge also demonstrated significantly reduced renal pathology and proteinuria. Microarray expression profiling prioritized two candidate genes for blood pressure regulation (Dnm1, Tor1b), localized within the common congenic interval shared by SP.WKYGla3d and SP.WKYGla3f strains, and one candidate gene for salt-induced PP variability and renal pathology (Rabgap1), located within the region unique to the SP.WKYGla3d strain. Comparison of next-generation sequencing data identified variants within additional positional genes that are likely to affect protein function. Conclusion: This study has identified distinct intervals on RNO3-containing genes that may be important for blood pressure regulation and renal pathology during salt challenge

    Thin static charged dust Majumdar-Papapetrou shells with high symmetry in D >= 4

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    We present a systematical study of static D >= 4 space-times of high symmetry with the matter source being a thin charged dust hypersurface shell. The shell manifold is assumed to have the following structure S_(beta) X R^(D-2-beta), beta (in the interval ) is dimension of a sphere S_(beta). In case of (beta) = 0, we assume that there are two parallel hyper-plane shells instead of only one. The space-time has Majumdar-Papapetrou form and it inherits the symmetries of the shell manifold - it is invariant under both rotations of the S_(beta) and translations along R^(D-2-beta). We find a general solution to the Einstein-Maxwell equations with a given shell. Then, we examine some flat interior solutions with special attention paid to D = 4. A connection to D = 4 non-relativistic theory is pointed out. We also comment on a straightforward generalisation to the case of Kastor-Traschen space-time, i.e. adding a non-negative cosmological constant to the charged dust matter source.Comment: Accepted in Int. J. Theor. Phy

    Een analyse van de toepassingsmogelijkheden van life cycle costing in een industriële omgeving

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    In dit artikel wordt een analyse gegeven van de toepassingsmogelijkheden van het Life Cycle Costing concept bij aanschaf-c.q. ontwerpbeslissingen van duurzame technische productiemiddelen in een industriele omgeving. Ten behoeve van deze analyse wordt het Life Cycle Costing concept vergeleken met de traditionele bedrijfseconomische beslissingscalculaties. Bovendien wordt middels gestructureerde interviews van bedrijfsfunctionarissen die (mede)verantwoordelijk zijn voor het aanschatheleid in hun ondememing een beeld gegeven van de praktische potenties van het concept. Uit de analyse en de interviews blijkt dat meer waarde gehecht moet worden aan het ontwikkelen van compensatiemogelijkheden, zoals modificatie en lease-constructies, bij eventuele onjuiste inschattingen. Verder onderzoek in deze is wenselijk

    Stated Preferences of Physicians and Chronic Pain Sufferers in the Use of Classic Strong Opioids

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    AbstractWe conducted a two-stage study in France, Germany, Italy, Spain, Sweden, and the United Kingdom of the stated preferences of chronic pain sufferers treated with classic strong opioids and of physicians treating such patients. The qualitative stage identified attributes perceived important through focus groups with 84 pain sufferers and semistructured interviews with 11 physicians. The quantitative stage included online, discrete choice experiments (DCEs) in which respondents chose between hypothetical profiles or an opt-out in 15 choice tasks. The profile descriptions were based on the attributes elicited in the qualitative stage. DCEs were conducted for pain sufferers (N = 242) and physicians (N = 270) who passed a rationality test. Main-effects models were estimated by hierarchical Bayesian regression. Sufferers ranked nausea, pain impact, energy, alertness, and constipation; physicians ranked pain response, central nervous system (CNS) effects, nausea, dose form, and constipation in descending order of importance. Sufferers were unwilling to incur severe side effects to decrease pain and chose the opt-out in approximately one half of the choice tasks, whereas physicians were willing to trade between profiles. The models predicted physicians' choices better than those of pain sufferers. No age, sex, or country effects were seen, but stronger preferences were found among physicians treating noncancer (n = 40) than cancer pain and among the 55% of sufferers who had never discontinued long-term pain medication use. Sufferers' mean pain scores on an 11-point Likert scale were 4.0, 5.7, and 8.6 on their best, average, and worst days, respectively

    Scheme and Scale Dependence of Charm Production in Neutrino Scattering

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    We discuss some theoretical uncertainties in the calculation of the cross section for charm production in charged current deep inelastic neutrino scattering related to ambiguities in the treatment of terms which are singular in the limit of a vanishing charm mass. In particular we compare the so-called variable flavour scheme where these terms are absorbed in the parton distribution functions containing the charm as an active flavour, with the so-called fixed flavour scheme with no charm mass subtraction where the charm appears only in the final state of fixed-order scattering matrix elements. Using available parametrizations of parton distribution functions we find that the two schemes lead to largely differing results for separate structure functions whereas the differences cancel to a large extent in the total cross section in that kinematical region which has been measured so far.Comment: 20pages, uuencoded postscript, figures include

    Photo--assisted current and shot noise in the fractional quantum Hall effect

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    The effect of an AC perturbation on the shot noise of a fractional quantum Hall fluid is studied both in the weak and the strong backscattering regimes. It is known that the zero-frequency current is linear in the bias voltage, while the noise derivative exhibits steps as a function of bias. In contrast, at Laughlin fractions, the backscattering current and the backscattering noise both exhibit evenly spaced singularities, which are reminiscent of the tunneling density of states singularities for quasiparticles. The spacing is determined by the quasiparticle charge νe\nu e and the ratio of the DC bias with respect to the drive frequency. Photo--assisted transport can thus be considered as a probe for effective charges at such filling factors, and could be used in the study of more complicated fractions of the Hall effect. A non-perturbative method for studying photo--assisted transport at ν=1/2\nu=1/2 is developed, using a refermionization procedure.Comment: 14 pages, 6 figure
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