24 research outputs found

    Mycophenolate mofetil decreases endothelial prostaglandin E-2 in response to allogeneic T cells or cytokines

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    Background. Prostaglandin E-2 (PGE(2)) is a powerful endogenous immune suppressant and interferes with various T-cell functions. However, it is not known in detail whether immunosuppressive drugs influence the PGE(2)-driven immune response in transplant patients. Therefore, we investigated the effect of several immunosuppressive compounds, in particular the novel drug mycophenolate mofetil (MMF), on endothelial PGE(2) release. Methods. Endothelial cells (HUVEC) were activated by either allogeneic CD4(+) or CD8(+) T cells, or by the cytokines interleukin-1 or gamma-interferon, Using an enzyme-linked immunosorbent assay, we analyzed PGE(2) release of the activated HUVEC in the presence of MMF, cyclosporine, or tacrolimus. As verapamil and mibefradil also possess immunosuppressive properties, they were included in the study as well. Results. Activation of HUVEC with interleukin-1 or T cells resulted in a drastic accumulation of PGE(2) in the supernatant. Cyclosporine or tacrolimus had no effect on PGE(2) release. However, Ca2+ channel blockers, when applied at higher dosages, caused a significant increase in PGE(2). Interestingly, MMF strongly diminished the PGE(2) level in the cell culture supernatant in a concentration-dependent manner. Conclusion. The results demonstrate an inhibitory effect of MMF on PGE(2) production, which may lower the benefits of the PGE(2)-triggered immune response after organ transplantation

    The immunosuppressive drug mycophenolate mofetil impairs the adhesion capacity of gastrointestinal tumour cells

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    Immunosuppression correlates with the development and recurrence of cancer. Mycophenolate mofetil (MMF) has been shown to reduce adhesion molecule expression and leucocyte recruitment into the donor organ. We have hypothesized that MMF might also prevent receptor-dependent tumour dissemination. Therefore, we have investigated the effects of MMF on tumour cell adhesion to human umbilical vein endothelial cells (HUVEC) and compared them with the effects on T cell-endothelial cell interactions. Influence of MMF on cellular adhesion to HUVEC was analysed using isolated CD4(+) and CD8(+) T cells, or WiDr colon adenocarcinoma cells as the model tumour. HUVEC receptors ICAM-1, VCAM-1, E-selectin and P-selectin were detected by flow cytometry, Western blot or Northern blot analysis. Binding activity of T cells or WiDr cells in the presence of MMF were measured using immobilized receptor globulin chimeras. MMF potently blocked both T cell and WiDr cell binding to endothelium by 80%. Surface expression of the endothelial cell receptors was reduced by MMF in a dose-dependent manner. E-selectin mRNA was concurrently reduced with a maximum effect at 1 mum. Interestingly, MMF acted differently on T cells and WiDr cells. Maximum efficacy of MMF was reached at 10 and 1 mum, respectively. Furthermore, MMF specifically suppressed T cell attachment to ICAM-1, VCAM-1 and P-selectin. In contrast, MMF prevented WiDr cell attachment to E-selectin. In conclusion, our data reveal distinct effects of MMF on both T cell adhesion and tumour cell adhesion to endothelial cells. This suggests that MMF not only interferes with the invasion of alloactivated T cells, but might also be of value in managing post-transplantation malignancy

    Interaction design for open innovation platforms: A social exchange perspective

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    We investigate the interaction design preferences of solution seekers and problem solvers on open innovation (crowdsourcing) platforms. Drawing on social exchange theory (SET), we hypothesize that seekers and solvers have different preferences for the configuration of four central interaction design features of a crowdsourcing platform: communication channels, collaboration options, selection of winning submissions, and feedback mechanisms. Based on a conjoint study with 842 respondents, we show conflicting preferences for the configuration of these features, but also find a surprisingly consistent “best” configuration that can balance the individual preferences of both seekers and solvers. In addition, we identify social trust, risk aversion, and the need for cognition as three personal characteristics of individuals in seeker organizations and solvers that influence their preferred configuration of platform design. Our findings help intermediaries operating a crowdsourcing platform to offer nuanced platform interactions that align how individuals in seeker organizations (e.g., project managers) and individual solvers create and capture value in crowdsourcing. Furthermore, we contribute to the micro-foundations of open innovation by proposing SET as a novel perspective to examine how the expectations and value drivers of all parties involved in a crowdsourcing project can be balanced

    Analysis of elemental concentrations of particle matter samples collected in a hyperarid environment in Namibia (Metadata RADIATE TA Proposal 23003138-ST)

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    <p>Proposal title "Analysis of elemental concentrations of particle matter samples collected in a hyperarid environment in Namibia". Measurements carried out at the external beam set-up for atmospheric aerosol analysis of the INFN LABEC accelerator laboratory), from 19 till 21 April 2023. Hands-off mode.</p>\n\n<p>A sampling campaign was carried out in April 2022 at the Gobabeb Namib Research Institute (GNRI; https://gobabeb.org/), in the Namib Desert of Namibia (-23.55 S, 15.03 E). Aerosol samples were collected for a three-week period on polytetrafluoroethylene filters (PTFE; Whatman; 47 mm in diameter, 2.0 μm pore size) both on the PM1 and PM10 fractions using homemade filter samplers from certified Leckel sampling heads (Sven Leckel, Germany).</p>\n\n<p><br>\nThe main objective is to measure the elemental composition of these samples by PIXE to evaluate for the first time (1) the source apportionment and relative contribution of the mineral dust and advected marine aerosols to the total aerosol mass; (2) the total<br>\nconcentrations of elements possibly soluble in water (sulfur, iron, phosphorous) forming clouds and/or contributing to ocean productivity. Complementary measurements with ion chromatography and ICP are performed at LISA.</p>\n\n<p>40 PM10 and 40 PM1 samples (including blanks) were analysed by PIXE, obtaining the concentrations of all elements with Z>10. In particular all main elements of interest (Na, Mg, Al, Si, P, S, Cl, K, Ca, Ti, V, Mn, Fe, Cu and Zn) were detected. A set of elemental standards were analyzed as well for quality assurance purposes and to check the accuracy of quantitative results.</p>\n\n<p><br>\nA 2.7 MeV proton beam was used. This energy was chosen to minimise the gamma ray emission from F in the collecting membranes, i.e. avoiding strong resonances in the 19F(p,p'γ)19F inelastic reactions (110 e 197 keV gamma-rays), that will increase the continuous background in the PIXE spectra in the energy region > 10 keV, increase pile-up and dead-time effects. This was particularly important for this experiment as the PTFE membranes used in this project are indeed quite thick. To identify the best working energy we<br>\nused literature data (Zamboni et al. NIM B 342, 2015, 266), and also measured Fluorine gamma-ray yield over a limited proton energy range of interest.<br>\n </p&gt

    The effect of metal type and loading on n-paraffin hydrocracking conversion and selectivity

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    Includes bibliographical references.With the continued decline in global oil reserves, there is a growing need to develop alternative sources of conventional fuels to complement the current dependence on crude oil feedstocks. Natural gas, coal and biomass have been identified for this purpose. The distinctive advantage of using natural (stranded) gas is that it is turned into a useful product, thereby increasing its value and reducing the environmental impact of simply flaring it. The value-added work up of natural gas is effected by Gas-to-Liquid conversion via the Fischer-Tropsch Synthesis. Long-chain hydrocarbon waxes are produced and these are subsequently hydrocracked into the required middle distillate fuels, preferably diesel, as diesel engines are more efficient than their petrol counterparts. Hydrocracking may be carried out using a bifunctional catalyst, consisting of metal and acid components. Industrially, hydrocracking is used to crack heavy crude oil fractions into the desired fuel range, however, the catalysts used are sulphided transition metals. These are less suitable for cracking Fischer-Tropsch waxes as they would introduce sulphur into a clean feedstock. Moreover, at reaction temperatures of around 250°C, transition metal sulphide catalysts display little activity. Thus, one may consider noble metals such as palladium or platinum, whilst shape selective zeolites may be used as the acid component

    Study of the uniformity of aerosol filters by scanning MA-XRF

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    Abstract: Energy-dispersive X-ray fluorescence (XRF) is an attractive analytical method to determine the level of air pollution by heavy metals. The concentration of the filter in ng/cm(2) is obtained by direct comparison of the net characteristic line intensity of an element with that of a thin film standard. As the sampled area on the filter and the area of the standard are larger than the area analysed by the instrument, the distribution of the elements on the surface of both samples and standards have to be sufficiently uniform. If this is not the case, biased concentration estimates are obtained. Two scanning macro-XRF setups with a beam diameter of similar to 0.5 mm were used to investigate the distribution of elements in (1) commercially available (Micromatter) standards, (2) in-house quartz filter standards obtained with an aerosol generator and (3) particulatematter (PM10) collected on quartz filters by a Leckel SEQ 47/50 sampler. The uniformity of the Micromatter standards was better than 2%. At least some in-house standards showed a concave distribution with less material at the edges. The maximum bias introduced by this is less than 5%. Because of the limited sensitivity of scanning XRF compared with conventional XRF, the distribution of only a few common elements like Ca and Fe could be determined reliably in aerosol filters. The distribution of some heavy elements could only be measured in filters sampled in polluted regions. In general, the loading of particulate matter over the filters was uniform. Copyright (C) 2017 John Wiley & Sons, Ltd
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