361 research outputs found

    Epistemic dispositions. Reply to Turri and Bronner

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    We reply to recent papers by John Turri and Ben Bronner, who criticise the dispositionalised Nozickian tracking account we discuss in “Mad, Bad and Dangerous to Know.” We argue that the account we suggested can handle the problems raised by Turri and Bronner. In the course of responding to Turri and Bronner’s objections, we draw three general lessons for theories of epistemic dispositions: that epistemic dispositions are to some extent extrinsic, that epistemic dispositions can have manifestation conditions concerning circumstances where their bearers fail to exist, and that contrast is relevant to disposition attributions

    Trust and temporality in participatory research

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    This paper argues that trust cannot be taken for granted in long-term participatory research and promotes greater consideration to conceptualizing the trusting process as fluid and fragile. This awareness by researchers can reveal to them how the passing of time shapes and reshapes the nature of trusting relationships and their constant negotiation and re-negotiation. The paper draws together literature from different disciplines on the themes of trust, temporality and participatory research and outcomes from interviews and workshops undertaken for The Trust Map project to focus on two key moments that reveal the fragility of trust. These are the subtlety of disruption and trust on trial and trust at a distance. We discuss how trust was built over time through processes of interaction that were continually tested, incremental and participatory

    Bovine Gamma Delta T Cells Contribute to Exacerbated IL-17 Production in Response to Co-Infection with Bovine RSV and Mannheimia haemolytica

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    Citation: McGill, J. L., Rusk, R. A., Guerra-Maupome, M., Briggs, R. E., & Sacco, R. E. (2016). Bovine Gamma Delta T Cells Contribute to Exacerbated IL-17 Production in Response to Co-Infection with Bovine RSV and Mannheimia haemolytica. Plos One, 11(3), 20. doi:10.1371/journal.pone.0151083Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovine RSV (BRSV) is genetically closely related to HRSV and is a leading cause of severe respiratory infections in young cattle. While BRSV infection in the calf parallels many aspects of human infection with HRSV, IL-17 and Th17 responses have not been studied in the bovine. Here we demonstrate that calves infected with BRSV express significant levels of IL-17, IL-21 and IL-22; and both CD4 T cells and Upsilon delta T cells contribute to this response. In addition to causing significant morbidity from uncomplicated infections, BRSV infection also contributes to the development of bovine respiratory disease complex (BRDC), a leading cause of morbidity in both beef and dairy cattle. BRDC is caused by a primary viral infection, followed by secondary bacterial pneumonia by pathogens such as Mannheimia haemolytica. Here, we demonstrate that in vivo infection with M. haemolytica results in increased expression of IL-17, IL-21 and IL-22. We have also developed an in vitro model of BRDC and show that co-infection of PBMC with BRSV followed by M. haemolytica leads to significantly exacerbated IL-17 production, which is primarily mediated by IL-17-producing Upsilon delta T cells. Together, our results demonstrate that calves, like humans, mount a robust IL-17 response during RSV infection; and suggest a previously unrecognized role for IL-17 and Upsilon delta T cells in the pathogenesis of BRDC

    Detection of Crab Giant Pulses Using the Mileura Widefield Array Low Frequency Demonstrator Field Prototype System

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    We report on the detection of giant pulses from the Crab Nebula pulsar at a frequency of 200 MHz using the field deployment system designed for the Mileura Widefield Array's Low Frequency Demonstrator (MWA-LFD). Our observations are among the first high-quality detections at such low frequencies. The measured pulse shapes are deconvolved for interstellar pulse broadening, yielding a pulse-broadening time of 670±\pm100 ÎŒ\mus, and the implied strength of scattering (scattering measure) is the lowest that is estimated towards the Crab nebula from observations made so far. The sensitivity of the system is largely dictated by the sky background, and our simple equipment is capable of detecting pulses that are brighter than ∌\sim9 kJy in amplitude. The brightest giant pulse detected in our data has a peak amplitude of ∌\sim50 kJy, and the implied brightness temperature is 1031.610^{31.6} K. We discuss the giant pulse detection prospects with the full MWA-LFD system. With a sensitivity over two orders of magnitude larger than the prototype equipment, the full system will be capable of detecting such bright giant pulses out to a wide range of Galactic distances; from ∌\sim8 to ∌\sim30 kpc depending on the frequency. The MWA-LFD will thus be a highly promising instrument for the studies of giant pulses and other fast radio transients at low frequencies.Comment: 10 pages, 6 figures, Accepted for publication in the Astrophysical Journa

    Improved genome editing in human cell lines using the CRISPR method

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    The Cas9/CRISPR system has become a popular choice for genome editing. In this system, binding of a single guide (sg) RNA to a cognate genomic sequence enables the Cas9 nuclease to induce a double-strand break at that locus. This break is next repaired by an error-prone mechanism, leading to mutation and gene disruption. In this study we describe a range of refinements of the method, including stable cell lines expressing Cas9, and a PCR based protocol for the generation of the sgRNA. We also describe a simple methodology that allows both elimination of Cas9 from cells after gene disruption and re-introduction of the disrupted gene. This advance enables easy assessment of the off target effects associated with gene disruption, as well as phenotype-based structure-function analysis. In our study, we used the Fan1 DNA repair gene as control in these experiments. Cas9/CRISPR-mediated Fan1 disruption occurred at frequencies of around 29%, and resulted in the anticipated spectrum of genotoxin hypersensitivity, which was rescued by re-introduction of Fan1

    Image-based monitoring for early detection of fouling in crystallisation processes

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    Fouling or encrustation is a significant problem in continuous crystallisation processes where crystal deposits at surfaces impede heat transfer, increase flow resistance and reduce product quality. This paper proposes an automatic algorithm to detect early stages of fouling using images of vessel surfaces from commodity cameras. Statistical analysis of the pixel intensity variation offers the ability to distinguish appearance of crystals in the bulk solution and on the crystalliser walls. This information is used to develop a fouling metric indicator and determine separately induction times for appearance of first crystals at the surfaces and in the bulk. A method to detect process state changes using Bayesian online change point detection is also proposed, where the first change point is used to determine induction time either at the surface or in the bulk, based on real-time online measurements without using any predetermined threshold which usually varies between experiments and depends on data acquisition equipment. This approach can be used for in situ monitoring of early signs of encrustation to allow early warning for corrective actions to be taken when operating continuous crystallisation processes
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