449 research outputs found

    Simple Viscous Flows: from Boundary Layers to the Renormalization Group

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    The seemingly simple problem of determining the drag on a body moving through a very viscous fluid has, for over 150 years, been a source of theoretical confusion, mathematical paradoxes, and experimental artifacts, primarily arising from the complex boundary layer structure of the flow near the body and at infinity. We review the extensive experimental and theoretical literature on this problem, with special emphasis on the logical relationship between different approaches. The survey begins with the developments of matched asymptotic expansions, and concludes with a discussion of perturbative renormalization group techniques, adapted from quantum field theory to differential equations. The renormalization group calculations lead to a new prediction for the drag coefficient, one which can both reproduce and surpass the results of matched asymptotics

    Virological failure after 1 year of first-line ART is not associated with HIV minority drug resistance in rural Cameroon

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    Objectives The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon. Methods In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls. Results At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm3 lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence. Conclusions Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy succes

    Monte-Carlo Simulations of Radiation-Induced Activation in a Fast-Neutron and Gamma- Based Cargo Inspection System

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    An air cargo inspection system combining two nuclear reaction based techniques, namely Fast-Neutron Resonance Radiography and Dual-Discrete-Energy Gamma Radiography is currently being developed. This system is expected to allow detection of standard and improvised explosives as well as special nuclear materials. An important aspect for the applicability of nuclear techniques in an airport inspection facility is the inventory and lifetimes of radioactive isotopes produced by the neutron and gamma radiation inside the cargo, as well as the dose delivered by these isotopes to people in contact with the cargo during and following the interrogation procedure. Using MCNPX and CINDER90 we have calculated the activation levels for several typical inspection scenarios. One example is the activation of various metal samples embedded in a cotton-filled container. To validate the simulation results, a benchmark experiment was performed, in which metal samples were activated by fast-neutrons in a water-filled glass jar. The induced activity was determined by analyzing the gamma spectra. Based on the calculated radioactive inventory in the container, the dose levels due to the induced gamma radiation were calculated at several distances from the container and in relevant time windows after the irradiation, in order to evaluate the radiation exposure of the cargo handling staff, air crew and passengers during flight. The possibility of remanent long-lived radioactive inventory after cargo is delivered to the client is also of concern and was evaluated.Comment: Proceedings of FNDA 201

    Topic Modeling as a Strategy of Inquiry in Organizational Research: A Tutorial With an Application Example on Organizational Culture

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    Research has emphasized the limitations of qualitative and quantitative approaches to studying organizational phenomena. For example, in-depth interviews are resource-intensive, while questionnaires with closed-ended questions can only measure predefined constructs. With the recent availability of large textual data sets and increased computational power, text mining has become an attractive method that has the potential to mitigate some of these limitations. Thus, we suggest applying topic modeling, a specific text mining technique, as a new and complementary strategy of inquiry to study organizational phenomena. In particular, we outline the potentials of structural topic modeling for organizational research and provide a step-by-step tutorial on how to apply it. Our application example builds on 428,492 reviews of Fortune 500 companies from the online platform Glassdoor on which employees can evaluate organizations. We demonstrate how structural topic models allow to inductively identify topics that matter to employees and to quantify their relationship with employees' perception of organizational culture. We discuss the advantages and limitations of topic modeling as a research method and outline how future research can apply the technique to study organizational phenomena

    Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

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    Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

    Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

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    Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies

    Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

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    9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe

    A Sucrose Solution Application to the Study of Model Biological Membranes

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    The small-angle X-ray and neutron scattering, time resolved X-ray small-angle and wide-angle diffraction coupled with differential scanning calorimetry have been applied to the investigation of unilamellar and multilamellar dimyristoylphosphatidylcholine (DMPC) vesicles in sucrose buffers with sucrose concentrations from 0 to 60%. Sucrose buffer decreased vesicle size and polydispersity and increased an X-ray contrast between phospholipid membrane and bulk solvent sufficiently. No influence of sucrose on the membrane thickness or mutual packing of hydrocarbon chains has been detected. The region of sucrose concentrations 30%-40% created the best experimental conditions for X-ray small-angle experiments with phospholipid vesicles.Comment: PDF: 10 pages, 6 figures. MS Word sours
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