150 research outputs found
Messenger RNA electroporation: an efficient tool in immunotherapy and stem cell research.
Over the last decades medicine has developed tremendously, but still many diseases are incurable. The last years, cellular (gene) therapy has become a hot topic in biomedical research for the potential treatment of cancer, AIDS and diseases involving cell loss or degeneration. Here, we will focus on two major areas within cellular therapy, cellular immunotherapy and stem cell therapy, that could benefit from the introduction of neo-expressed genes through mRNA electroporation for basic research as well as for clinical applications. For cellular immunotherapy, we will provide a state-of-the-art on loading antigen-presenting cells with antigens in the mRNA format for manipulation of T cell immunity. In the area of stem cell research, we will highlight current gene transfer methods into adult and embryonic stem cells and discuss the use of mRNA electroporation for controlling guided differentiation of stem cells into specialized cell lineages
The 0 and the pi phase Josephson coupling through an insulating barrier with magnetic impurities
We have studied temperature and field dependencies of the critical current
in the Nb-FeSi-Nb Josephson junction with tunneling
barrier formed by paramagnetic insulator. We demonstrate that in these
junctions the co-existence of both the 0 and the states within one tunnel
junction takes place which leads to the appearance of a sharp cusp in the
temperature dependence similar to the cusp found for the
transition in metallic junctions. This cusp is not related to the
temperature induced transition itself, but is caused by the different
temperature dependencies of the opposing 0 and supercurrents through the
barrier.Comment: Accepted in Physical Review
Observation and Assignment of Silent and Higher Order Vibrations in the Infrared Transmission of C60 Crystals
We report the measurement of infrared transmission of large C60 single
crystals. The spectra exhibit a very rich structure with over 180 vibrational
absorptions visible in the 100 - 4000 cm-1 range. Many silent modes are
observed to have become weakly IR-active. We also observe a large number of
higher order combination modes. The temperature (77K - 300K) and pressure (0 -
25KBar) dependencies of these modes were measured and are presented. Careful
analysis of the IR spectra in conjunction with Raman scattering data showing
second order modes and neutron scattering data, allow the selection of the 46
vibrational modes C60. We are able to fit *all* of the first and second order
data seen in the present IR spectra and the previously published Raman data
(~300 lines total), using these 46 modes and their group theory allowed second
order combinations.Comment: REVTEX v3.0 in LaTeX. 12 pages. 8 Figures by request. c60lon
Endothelial Microparticles (EMP) for the Assessment of Endothelial Function: An In Vitro and In Vivo Study on Possible Interference of Plasma Lipids
BACKGROUND: Circulating endothelial microparticles (EMP) reflect the condition of the endothelium and are of increasing interest in cardiovascular and inflammatory diseases. Recently, increased numbers of EMP following oral fat intake, possibly due to acute endothelial injury, have been reported. On the other hand, the direct interference of lipids with the detection of EMP has been suggested. This study aimed to investigate the effect of lipid-rich solutions, commonly administered in clinical practice, on the detection, both in vitro and in vivo, of EMP. METHODS: For the in vitro assessment, several lipid-rich solutions were added to whole blood of healthy subjects (nâ=â8) and patients with coronary heart disease (nâ=â5). EMP (CD31+/CD42b-) were detected in platelet poor plasma by flow cytometry. For the in vivo study, healthy volunteers were evaluated on 3 different study-days: baseline evaluation, following lipid infusion and after a NaCl infusion. EMP quantification, lipid measurements and peripheral arterial tonometry were performed on each day. RESULTS: Both in vitro addition and in vivo administration of lipids significantly decreased EMP (from 198.6 to 53.0 and from 272.6 to 90.6/”l PPP, respectively, pâ=â0.001 and pâ=â0.012). The EMP number correlated inversely with the concentration of triglycerides, both in vitro and in vivo (râ=â-0.707 and -0.589, p<0.001 and pâ=â0.021, respectively). The validity of EMP as a marker of endothelial function is supported by their inverse relationship with the reactive hyperemia index (râ=â-0.758, pâ=â0.011). This inverse relation was confounded by the intravenous administration of lipids. CONCLUSION: The confounding effect of high circulating levels of lipids, commonly found in patients that receive intravenous lipid-based solutions, should be taken into account when flow cytometry is used to quantify EMP
Structural and luminescence investigation on gadolinium gallium garnet nanocrystalline powders prepared by solution combustion synthesis
Nanocrystalline powders of undoped and lanthanide (Pr3+, Tm3+)- doped gadolinium gallium garnet, Gd3Ga5O12 (GGG), were prepared by propellant synthesis and studied by x-ray powder diffraction (XRD), electron diffraction (ED), high-resolution electron microscopy (HREM) and luminescence spectroscopy. The x-ray diffraction patterns of the GGG samples were analysed using the Rietveld method. The Rietveld refinement reveals the existence of two garnet-type phases: both are cubic (space group Ia d) with a slightly different lattice parameter and probably a slightly different composition. Electron diffraction and electron microscopy measurements confirm the x-ray diffraction results. EDX measurements for lanthanide-doped samples show that stable solid solutions with composition Gd(3-x)Ln(x)Ga(5)O(12), x approximate to 0.3 ( Ln = Pr; Tm) have been obtained. The luminescence properties of the Tm3+ -doped nanocrystalline GGG samples were measured and analysed
Poly(I:C) Enhances the Susceptibility of Leukemic Cells to NK Cell Cytotoxicity and Phagocytosis by DC
α Active specific immunotherapy aims at stimulating the host's immune system to recognize and eradicate malignant cells. The concomitant activation of dendritic cells (DC) and natural killer (NK) cells is an attractive modality for immune-based therapies. Inducing immunogenic cell death to facilitate tumor cell recognition and phagocytosis by neighbouring immune cells is of utmost importance for guiding the outcome of the immune response. We previously reported that acute myeloid leukemic (AML) cells in response to electroporation with the synthetic dsRNA analogue poly(I:C) exert improved immunogenicity, demonstrated by enhanced DC-activating and NK cell interferon-γ-inducing capacities. To further invigorate the potential of these immunogenic tumor cells, we explored their effect on the phagocytic and cytotoxic capacity of DC and NK cells, respectively. Using single-cell analysis, we assessed these functionalities in two- and three-party cocultures. Following poly(I:C) electroporation AML cells become highly susceptible to NK cell-mediated killing and phagocytosis by DC. Moreover, the enhanced killing and the improved uptake are strongly correlated. Interestingly, tumor cell killing, but not phagocytosis, is further enhanced in three-party cocultures provided that these tumor cells were upfront electroporated with poly(I:C). Altogether, poly(I:C)-electroporated AML cells potently activate DC and NK cell functions and stimulate NK-DC cross-talk in terms of tumor cell killing. These data strongly support the use of poly(I:C) as a cancer vaccine component, providing a way to overcome immune evasion by leukemic cells
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