42 research outputs found

    The sketch map tool facilitates the assessment of OpenStreetMap data for participatory mapping

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    A worldwide increase in the number of people and areas affected by disasters has led to more and more approaches that focus on the integration of local knowledge into disaster risk reduction processes. The research at hand shows a method for formalizing this local knowledge via sketch maps in the context of flooding. The Sketch Map Tool enables not only the visualization of this local knowledge and analyses of OpenStreetMap data quality but also the communication of the results of these analyses in an understandable way. Since the tool will be open-source and several analyses are made automatically, the tool also offers a method for local governments in areas where historic data or financial means for flood mitigation are limited. Example analyses for two cities in Brazil show the functionalities of the tool and allow the evaluation of its applicability. Results depict that the fitness-for-purpose analysis of the OpenStreetMap data reveals promising results to identify whether the sketch map approach can be used in a certain area or if citizens might have problems with marking their flood experiences. In this way, an intrinsic quality analysis is incorporated into a participatory mapping approach. Additionally, different paper formats offered for printing enable not only individual mapping but also group mapping. Future work will focus on advancing the automation of all steps of the tool to allow members of local governments without specific technical knowledge to apply the Sketch Map Tool for their own study areas

    IL-17+ CD8+ T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis

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    IL-17-producing CD8+ (Tc17) cells are enriched in active lesions of patients with multiple sclerosis (MS), suggesting a role in the pathogenesis of autoimmunity. Here we show that amelioration of MS by dimethyl fumarate (DMF), a mechanistically elusive drug, associates with suppression of Tc17 cells. DMF treatment results in reduced frequency of Tc17, contrary to Th17 cells, and in a decreased ratio of the regulators RORC-to-TBX21, along with a shift towards cytotoxic T lymphocyte gene expression signature in CD8+ T cells from MS patients. Mechanistically, DMF potentiates the PI3K-AKT-FOXO1-T-BET pathway, thereby limiting IL-17 and RORÎłt expression as well as STAT5-signaling in a glutathione-dependent manner. This results in chromatin remodeling at the Il17 locus. Consequently, T-BET-deficiency in mice or inhibition of PI3K-AKT, STAT5 or reactive oxygen species prevents DMF-mediated Tc17 suppression. Overall, our data disclose a DMF-AKT-T-BET driven immune modulation and suggest putative therapy targets in MS and beyond

    Elective haemodialysis increases exhaled isoprene

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    Uraemic odour is a characteristic feature of patients with end-stage renal disease (ESRD). However, few investigations have been carried out into the composition of exhaled air in ESRD patients undergoing haemodialysis (HD). Increases of exhaled isoprene levels by a factor of up to 2.7 following HD have been reported. We attempted to confirm these findings in 50 patients undergoing HD using haemophan (n=23) or polysulphone (n=27) dialysis membranes. Parallel evaluation of ambient air, calorie intake, medication and haemodynamic variables was performed. Samples were analysed using proton transfer reaction-mass spectrometry (PTR-MS). Significant changes in breath isoprene concentration were observed when comparing patients before [39.14+/-14.96 parts per billion (ppbv)] and after (63.54+/-27.59 ppbv) dialysis (P <0.001). The quotient of values before and after dialysis was 1.84 (SD 1.41). No significant differences in isoprene kinetics were found between the use of haemophan and polysulphone membranes. No significant correlations were observed between isoprene quotients and variations in blood pressure during HD, calorie intake, ingestion of lipid-lowering drugs or serum lipid levels. Isoprene concentration was higher in the exhaled air of patients after HD as compared with values before HD. Large interindividual variability existed in isoprene kinetics. Oxidative stress appears to be an unlikely cause for this rise. An alternative hypothesis is an influence of respiratory variables on isoprene exhalation based upon Henry's law constant. We therefore propose to perform online monitoring of isoprene exhalation by PTR-MS during the HD session to investigate the possible influence of respiratory variable

    CD3-Positive B Cells: A Storage-Dependent Phenomenon

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    <div><p>The majority of clinical studies requires extensive management of human specimen including e.g. overnight shipping of blood samples in order to convey the samples in a central laboratory or to simultaneously analyze large numbers of patients. Storage of blood samples for periods of time before <i>in vitro</i>/<i>ex vivo</i> testing is known to influence the antigen expression on the surface of lymphocytes. In this context, the present results show for the first time that the T cell antigen CD3 can be substantially detected on the surface of human B cells after <i>ex vivo</i> storage and that the degree of this phenomenon critically depends on temperature and duration after blood withdrawal. The appearance of CD3 on the B cell surface seems to be a result of contact-dependent antigen exchange between T and B lymphocytes and is not attributed to endogenous production by B cells. Since cellular subsets are often classified by phenotypic analyses, our results indicate that <i>ex vivo</i> cellular classification in peripheral blood might result in misleading interpretations. Therefore, in order to obtain results reflecting the <i>in vivo</i> situation, it is suggested to minimize times of <i>ex vivo</i> blood storage after isolation of PBMC. Moreover, to enable reproducibility of results between different research groups and multicenter studies, we would emphasize the necessity to specify and standardize the storage conditions, which might be the basis of particular findings.</p></div

    Detection of the T cell antigens CD3 and CD4 on CD20<sup>+</sup> lymphocytes by flow cytometry.

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    <p>The appearance of both CD3 (A) and CD4 antigens (B) on the surface of CD20<sup>+</sup> lymphocytes is shown for one representative patient. Freshly isolated lymphocytes (left) were compared to lymphocytes analyzed after overnight (oN) storage of whole blood samples at 4°C (right). The statistically significant difference in the number of CD3-expressing CD20<sup>+</sup> (CD3<sup>low</sup>CD20<sup>+</sup>) lymphocytes between two independent groups of donors (fresh <i>versus</i> oN/4°C) was determined by the two-sided Mann-Whitney-U-Test. Outliers are depicted as circles.</p

    Numbers of CD3<sup>low</sup>CD20<sup>+</sup> B cells are time- and temperature-dependent.

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    <p>The increase in the number of CD3<sup>low</sup>CD20<sup>+</sup> B cells was time-dependent, but independent of storage conditions (4°C <i>versus</i> room temperature (RT) <i>versus</i> humidified atmosphere at 37°C, 5% CO<sub>2</sub>). CD3<sup>low</sup>CD20<sup>+</sup> B cells were detectable at earlier time points and more pronounced at 4°C storage compared to RT and 37°C incubation, respectively. Shown are the results of two independent experiments performed in the same patient.</p

    Flt3L, LIF, and IL‐10 combination promotes the selective in vitro development of ESAMlow^{low} cDC2B from murine bone marrow

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    The development of two conventional dendritic cells (DC) subsets (cDC1 and cDC2) and the plasmacytoid DC (pDC) in vivo and in cultures of bone marrow (BM) cells is mediated by the growth factor Flt3L. However, little is known about the factors that direct the development of the individual DC subsets. Here, we describe the selective in vitro generation of murine ESAMlow^{low} CD103−^{-} XCR1−^{-} CD172a+^{+} CD11b+^{+} cDC2 from BM by treatment with a combination of Flt3L, LIF, and IL‐10 (collectively named as FL10). FL10 promotes common dendritic cell progenitors (CDP) proliferation in the cultures, similar to Flt3L and CDP sorted and cultured in FL10 generate exclusively cDC2. These cDC2 express the transcription factors Irf4, Klf4, and Notch2, and their growth is reduced using BM from Irf4−/−^{-/-} mice, but the expression of Batf3 and Tcf4 is low. Functionally they respond to TLR3, TLR4, and TLR9 signals by upregulation of the surface maturation markers MHC II, CD80, CD86, and CD40, while they poorly secrete proinflammatory cytokines. Peptide presentation to TCR transgenic OT‐II cells induced proliferation and IFN‐γ production that was similar to GM‐CSF‐generated BM‐DC and higher than Flt3L‐generated DC. Together, our data support that FL10 culture of BM cells selectively promotes CDP‐derived ESAMlow^{low} cDC2 (cDC2B) development and survival in vitro
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