623 research outputs found

    Satire in the novels of Henry Fielding

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    Informed Consent for All! No Exceptions

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    A comparative analysis of parallel processing and super-individual methods for improving the computational performance of a large individual-based model

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    Individual-based modelling approaches are being used to simulate larger complex spatial systems in ecology and in other fields of research. Several novel model development issues now face researchers: in particular how to simulate large numbers of individuals with high levels of complexity, given finite computing resources. A case study of a spatially-explicit simulation of aphid population dynamics was used to assess two strategies for coping with a large number of individuals: the use of ‘super-individuals’ and parallel computing. Parallelisation of the model maintained the model structure and thus the simulation results were comparable to the original model. However, the super-individual implementation of the model caused significant changes to the model dynamics, both spatially and temporally. When super-individuals represented more than around 10 individuals it became evident that aggregate statistics generated from a super-individual model can hide more detailed deviations from an individual-level model. Improvements in memory use and model speed were perceived with both approaches. For the parallel approach, significant speed-up was only achieved when more than five processors were used and memory availability was only increased once five or more processors were used. The super-individual approach has potential to improve model speed and memory use dramatically, however this paper cautions the use of this approach for a density-dependent spatially-explicit model, unless individual variability is better taken into account

    Exploiting the neoantigen landscape for immunotherapy of pancreatic ductal adenocarcinoma

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    Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases. Our findings reveal that: (a) nearly all PDAC samples harbor potentially targetable neoantigens; (b) T cells are present but generally show a reduced activation signature; and (c) markers of efficient antigen presentation are associated with a reduced signature of markers characterizing cytotoxic T cells. These findings suggest that despite the presence of tumor specific neoepitopes, T cell activation is actively suppressed in PDAC. Further, we identify iNOS as a potential mediator of immune suppression that might be actionable using pharmacological avenues

    Using uncrewed aerial vehicles for identifying the extent of invasive phragmites australis in treatment areas enrolled in an adaptive management program

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    Higher spatial and temporal resolutions of remote sensing data are likely to be useful for ecological monitoring efforts. There are many different treatment approaches for the introduced European genotype of Phragmites australis, and adaptive management principles are being integrated in at least some long-term monitoring efforts. In this paper, we investigated how natural color and a smaller set of near-infrared (NIR) images collected with low-cost uncrewed aerial vehicles (UAVs) could help quantify the aboveground effects of management efforts at 20 sites enrolled in the Phragmites Adaptive Management Framework (PAMF) spanning the coastal Laurentian Great Lakes region. We used object-based image analysis and field ground truth data to classify the Phragmites and other cover types present at each of the sites and calculate the percent cover of Phragmites, including whether it was alive or dead, in the UAV images. The mean overall accuracy for our analysis with natural color data was 91.7% using four standardized classes (Live Phragmites, Dead Phragmites, Other Vegetation, Other Non-vegetation). The Live Phragmites class had a mean user’s accuracy of 90.3% and a mean producer’s accuracy of 90.1%, and the Dead Phragmites class had a mean user’s accuracy of 76.5% and a mean producer’s accuracy of 85.2% (not all classes existed at all sites). These results show that UAV-based imaging and object-based classification can be a useful tool to measure the extent of dead and live Phragmites at a series of sites undergoing management. Overall, these results indicate that UAV sensing appears to be a useful tool for identifying the extent of Phragmites at management sites

    Electrophysiological effects of 5-hydroxytryptamine on isolated human atrial myocytes, and the influence of chronic beta-adrenoceptor blockade

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    <b>1.</b> 5-Hydroxytryptamine (5-HT) has been postulated to play a proarrhythmic role in the human atria via stimulation of 5-HT<sub>4</sub> receptors. <b>2.</b> The aims of this study were to examine the effects of 5-HT on the L-type Ca<sup>2+</sup> current (<i>I</i><sub>CaL</sub>) action potential duration (APD), the effective refractory period (ERP) and arrhythmic activity in human atrial cells, and to assess the effects of prior treatment with β-adrenoceptor antagonists. <b>3.</b> Isolated myocytes, from the right atrial appendage of 27 consenting patients undergoing cardiac surgery who were in sinus rhythm, were studied using the whole-cell perforated patch-clamp technique at 37ºC. <b>4.</b> 5-HT (1 n-10 μM) caused a concentration-dependent increase in <i>I</i><sub>CaL</sub>, which was potentiated in cells from β-blocked (maximum response to 5-HT, E<sub>max</sub>=299±12% increase above control) compared to non-β-blocked patients (E<sub>max</sub>=220±6%, P<0.05), but with no change in either the potency (log EC<sub>50</sub>: -7.09±0.07 vs -7.26±0.06) or Hill coefficient (<i>n</i><sub>H</sub>: 1.5±0.6 vs 1.5±0.3) of the 5-HT concentration-response curve. <b>5.</b> 5-HT (10 μM) produced a greater increase in the APD at 50% repolarisation (APD50) in cells from β-blocked patients (of 37±10 ms, i.e. 589±197%) vs non-β-blocked patients (of 10±4 ms, i.e. 157±54%; P<0.05). Both the APD<sub>90</sub> and the ERP were unaffected by 5-HT. <b>6.</b> Arrhythmic activity was observed in response to 5-HT in five of 17 cells (29%) studied from β-blocked, compared to zero of 16 cells from the non-β-blocked patients (P<0.05). <b>7.</b> In summary, the 5-HT-induced increase in calcium current was associated with a prolonged early plateau phase of repolarisation, but not late repolarisation or refractoriness, and the enhancement of these effects by chronic β-adrenoceptor blockade was associated with arrhythmic potential
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