879 research outputs found

    Bacterial-epithelial contact is a key determinant of host innate immune responses to enteropathogenic and enteroaggregative escherichia coli

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    Background: Enteropathogenic (EPEC) and Enteroaggregative (EAEC) E. coli have similar, but distinct clinical symptoms and modes of pathogenesis. Nevertheless when they infect the gastrointestinal tract, it is thought that their flagellin causes IL-8 release leading to neutrophil recruitment and gastroenteritis. However, this may not be the whole story as the effect of bacterial adherence to IEC innate response(s) remains unclear. Therefore, we have characterized which bacterial motifs contribute to the innate epithelial response to EPEC and EAEC, using a range of EPEC and EAEC isogenic mutant strains. Methodology: Caco-2 and HEp-2 cell lines were exposed to prototypical EPEC strain E2348/69 or EAEC strain O42, in addition to a range of isogenic mutant strains. E69 [LPS, non-motile, non-adherent, type three secretion system (TTSS) negative, signalling negative] or O42 [non-motile, non-adherent]. IL-8 and CCL20 protein secretion was measured. Bacterial surface structures were assessed by negative staining Transmission Electron Microscopy. The Fluorescent-actin staining test was carried out to determine bacterial adherence. Results: Previous studies have reported a balance between the host pro-inflammatory response and microbial suppression of this response. In our system an overall balance towards the host pro-inflammatory response is seen with the E69 WT and to a greater extent O42 WT, which is in fit with clinical symptoms. On removal of the external EPEC structures flagella, LPS, BFP, EspA and EspC; and EAEC flagella and AAF, the host inflammatory response is reduced. However, removal of E69 lymphostatin increases the host inflammatory response suggesting involvement in the bacterial mediated anti-inflammatory response. Conclusion: Epithelial responses were due to combinations of bacterial agonists, with host-bacterial contact a key determinant of these innate responses. Host epithelial recognition was offset by the microbe's ability to down-regulate the inflammatory response. Understanding the complexity of this host-microbial balance will contribute to improved vaccine design for infectious gastroenteritis

    Microbial imbalance in inflammatory bowel disease patients at different taxonomic levels

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    Background Inflammatory bowel disease (IBD), is a debilitating group of chronic diseases including Crohn’s Disease (CD) and ulcerative colitis (UC), which causes inflammation of the gut and affects millions of people worldwide. At different taxonomic levels, the structure of the gut microbiota is significantly altered in IBD patients compared to that of healthy individuals. However, it is unclear how these IBD-affected bacterial groups are related to other common bacteria in the gut, and how they are connected across different disease conditions at the global scale. Results In this study, using faecal samples from patients with IBD, we show through diversity analysis of the microbial community structure based on the 16S rRNA gene that the gut microbiome of IBD patients is less diverse compared to healthy individuals. Furthermore, we have identified which bacterial groups change in abundance in both CD and UC compared to healthy controls. A substantial imbalance was observed across four major bacterial phyla including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria, which together constitute >98% of the gut microbiota. Next, we reconstructed a bacterial family co-abundance network based on the correlation of abundance profiles obtained from the public gut microbiome data of >22000 samples of faecal and gut biopsies taken from both diseased and healthy individuals. The data was compiled using the EBI metagenomics database [1]. By mapping IBD-altered bacterial families to the network, we show that the bacterial families which exhibit an increased abundance in IBD conditions are not well connected to other groups, implying that these families generally do not coexist together with common gut organisms. Whereas, the bacterial families whose abundance is reduced or did not change in IBD conditions compared to healthy conditions are very well connected to other bacterial groups, suggesting they are highly important groups of bacteria in the gut that can coexist with other bacteria across a range of conditions. Conclusions IBD patients exhibited a less diverse gut microbiome compared to healthy individuals. Bacterial groups which changed in IBD patients were found to be groups which do not co-exist well with common commensal gut bacteria, whereas bacterial groups which did not change in patients with IBD were found to commonly co-exist with commensal gut microbiota. This gives a potential insight into the dynamics of the gut microbiota in patients with IBD

    Practical Application of a Subscale Transport Aircraft for Flight Research in Control Upset and Failure Conditions

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    Over the past decade, the goal of reducing the fatal accident rate of large transport aircraft has resulted in research aimed at the problem of aircraft loss-of-control. Starting in 1999, the NASA Aviation Safety Program initiated research that included vehicle dynamics modeling, system health monitoring, and reconfigurable control systems focused on flight regimes beyond the normal flight envelope. In recent years, there has been an increased emphasis on adaptive control technologies for recovery from control upsets or failures including damage scenarios. As part of these efforts, NASA has developed the Airborne Subscale Transport Aircraft Research (AirSTAR) flight facility to allow flight research and validation, and system testing for flight regimes that are considered too risky for full-scale manned transport airplane testing. The AirSTAR facility utilizes dynamically-scaled vehicles that enable the application of subscale flight test results to full scale vehicles. This paper describes the modeling and simulation approach used for AirSTAR vehicles that supports the goals of efficient, low-cost and safe flight research in abnormal flight conditions. Modeling of aerodynamics, controls, and propulsion will be discussed as well as the application of simulation to flight control system development, test planning, risk mitigation, and flight research

    1864-10-25 A.F. Murch of Company E requests discharge due to wounds received at Gettysburg

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    https://digitalmaine.com/cw_me_3rd_regiment_corr/1577/thumbnail.jp

    Intensity-based image registration using multiple distributed agents

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    Image registration is the process of geometrically aligning images taken from different sensors, viewpoints or instances in time. It plays a key role in the detection of defects or anomalies for automated visual inspection. A multiagent distributed blackboard system has been developed for intensity-based image registration. The images are divided into segments and allocated to agents on separate processors, allowing parallel computation of a similarity metric that measures the degree of likeness between reference and sensed images after the application of a transform. The need for a dedicated control module is removed by coordination of agents via the blackboard. Tests show that additional agents increase speed, provided the communication capacity of the blackboard is not saturated. The success of the approach in achieving registration, despite significant misalignment of the original images, is demonstrated in the detection of manufacturing defects on screen-printed plastic bottles and printed circuit boards

    The Potential of TaqMan Array Cards for Detection of Multiple Biological Agents by Real-Time PCR

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    The TaqMan Array Card architecture, normally used for gene expression studies, was evaluated for its potential to detect multiple bacterial agents by real-time PCR. Ten PCR assays targeting five biological agents (Bacillus anthracis, Burkholderia mallei, Burkholderia pseudomallei, Francisella tularensis, and Yersinia pestis) were incorporated onto Array Cards. A comparison of PCR performance of each PCR in Array Card and singleplex format was conducted using DNA extracted from pure bacterial cultures. When 100 fg of agent DNA was added to Array Card channels the following levels of agent detection (where at least one agent PCR replicate returned a positive result) were observed: Y. pestis 100%, B. mallei & F. tularensis 93%; B. anthracis 71%; B. pseudomallei 43%. For B. mallei & pseudomallei detection the BPM2 PCR, which detects both species, outperformed PCR assays specific to each organism indicating identification of the respective species would not be reproducible at the 100 fg level. Near 100% levels of detection were observed when 100 fg of DNA was added to each PCR in singleplex format with singleplex PCRs also returning sporadic positives at the 10 fg per PCR level. Before evaluating the use of Array Cards for the testing of environmental and clinical sample types, with potential levels of background DNA and PCR inhibitors, users would therefore have to accept a 10-fold reduction in sensitivity of PCR assays on the Array Card format, in order to benefit for the capacity to test multiple samples for multiple agents. A two PCR per agent strategy would allow the testing of 7 samples for the presence of 11 biological agents or 3 samples for 23 biological agents per card (with negative control channels)
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