15,138 research outputs found

    Message from the President (of BSU)

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    Last night as a couple of my friends scrambled to find a classroom to do work in, they came across a poster that has been plastered all around campus for weeks now. This poster, however, was different. This poster was vandalized. The face of this year’s 10th Annual Derrick K. Gondwe Memorial Lecture, Opal Tometi, had been ripped off and the word “Black” was crossed out and replaced with the word “All.” This changed the quote from “Black Lives Matter” to “All Lives Matter.” [excerpt

    Evaluation of phylogenetic reconstruction methods using bacterial whole genomes: a simulation based study

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    Background: Phylogenetic reconstruction is a necessary first step in many analyses which use whole genome sequence data from bacterial populations. There are many available methods to infer phylogenies, and these have various advantages and disadvantages, but few unbiased comparisons of the range of approaches have been made. Methods: We simulated data from a defined "true tree" using a realistic evolutionary model. We built phylogenies from this data using a range of methods, and compared reconstructed trees to the true tree using two measures, noting the computational time needed for different phylogenetic reconstructions. We also used real data from Streptococcus pneumoniae alignments to compare individual core gene trees to a core genome tree. Results: We found that, as expected, maximum likelihood trees from good quality alignments were the most accurate, but also the most computationally intensive. Using less accurate phylogenetic reconstruction methods, we were able to obtain results of comparable accuracy; we found that approximate results can rapidly be obtained using genetic distance based methods. In real data we found that highly conserved core genes, such as those involved in translation, gave an inaccurate tree topology, whereas genes involved in recombination events gave inaccurate branch lengths. We also show a tree-of-trees, relating the results of different phylogenetic reconstructions to each other. Conclusions: We recommend three approaches, depending on requirements for accuracy and computational time. Quicker approaches that do not perform full maximum likelihood optimisation may be useful for many analyses requiring a phylogeny, as generating a high quality input alignment is likely to be the major limiting factor of accurate tree topology. We have publicly released our simulated data and code to enable further comparisons

    The transient start-up response of a universal exhaust gas oxygen sensor to investigate the Nernst equation in platinum/zirconia cells

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    The universal exhaust gas oxygen sensor (UEGO) is a device used to infer the combustion air-to-fuel ratio of an internal combustion engine by sampling the exhaust gas. The sensor operates using a feedback system to maintain a specified internal condition, and measures the oxygen current required for this. While the steady state operation of the sensor is reasonably well-understood - dominated as it is by the diffusion of gas species - the factors influencing the transient response are not so clear. In this paper a numerical model of a sensor is compared to experimental data. By examining the effect of the inclusion of different aspects into the model, it becomes clear that it is necessary to account for the influence of gaseous species adsorping onto surfaces, as well as the more traditional approach based on oxygen partial pressure, to correctly capture the transient response of a sensor containing a Pt|YSZ|Pt cell.The work undertaken was funded by the Engineering and Physical Sciences Research Council.This is the final version. It was first published by Elsevier at http://www.sciencedirect.com/science/journal/aip/09254005

    Sidelining Bias: A Situationist Approach to Reduce the Consequences of Bias in Real-World Contexts

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    It has become common practice to conceptualize bias as an automatic response, cultivated through exposure to bias in society. From this perspective, combating bias requires reducing a proclivity for bias within individuals, as in many implicit-bias training efforts common in schools and corporations. We introduce an alternative approach that begins with the presumption that people are inherently complex, with multiple, often contradictory, selves and goals. When the person is conceptualized this way, it is possible to ask when biased selves are likely to emerge and whether this bias can be sidelined—that is, whether situations can be altered in potent ways that elevate alternative selves and goals that people will endorse and for which bias would be nonfunctional. Using both classic and contemporary examples, we show how sidelining bias has led to meaningful improvements in real-world outcomes, including higher academic achievement and reduced school suspensions, less recidivism to jail, and less stereotyping in mass advertisements

    On the emissions and transport of bromoform: Sensitivity to model resolution and emission location

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    Abstract. Bromoform (CHBr3) is a short-lived species with an important but poorly quantified ocean source. It can be transported to the Tropical Tropopause Layer (TTL), in part by rapid, deep convective lifting, from where it can influence the global stratospheric ozone budget. In a modelling study, we investigate the importance of the regional distribution of the emissions and of model resolution for the transport of bromoform to the TTL. We use two idealized CHBr3 emission fields (one coastal, one uniformly distributed across the oceans) implemented in high- and coarse-resolution (HR and CR) versions of the same global model and focus on February as the period of peak convection in the West Pacific. Using outgoing long-wave radiation and precipitation as metrics, the HR version of the model is found to represent convection better. In the more realistic HR model version, the coastal emission scenario leads to 15–20 % more CHBr3 in the global TTL, and up to three times more CHBr3 in the TTL over the Maritime Continent, than when uniform emissions of the same tropical magnitude are employed. Using the uniform emission scenario in both model versions, the distribution of CHBr3 at 15.7 km (approximately the level of zero net radiative heating) is qualitatively consistent with the differing geographic distributions of convection. However, averaged over the whole tropics, the amount of CHBr3 in the TTL in the two model versions is similar. Using the coastal scenario, in which emissions are particularly high in the Maritime Continent because of its long coastlines, the mixing ratio of CHBr3 in the TTL is enhanced over the Maritime Continent in both model versions. The enhancement is larger, and the peak in CHBr3 mixing ratio occurs at a higher altitude, in the HR model version. Our regional-scale results indicate that using aircraft measurements and coarse global models to infer CHBr3 emissions will be very difficult, particularly if (as is possible) emissions are distributed heterogeneously and in regions of strong convective activity. In contrast, the global-scale agreement between our CR and HR calculations suggests model resolution is less vital for studies focused on the transport of bromine into the global stratosphere. This work was supported through the ERC ACCI project (project no. 267760), and by NERC through grant nos. NE/J006246/1 and NE/F1016012/1. N. R. P. Harris was supported by a NERC Advanced Research Fellowship (NE/G014655/1).This is the final version of the article. It first appeared from Copernicus Publications via http://dx.doi.org/10.5194/acp-15-14031-201

    In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

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    BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB
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