Rat Mesenchymal Stromal Cells Inhibit T Cell Proliferation but Not Cytokine Production Through Inducible Nitric Oxide Synthase

Mesenchymal stromal cells (MSC) have important immunomodulatory properties, they inhibit T lymphocyte allo-activation and have been used to treat graft-versus-host disease. How MSC exert their immunosuppressive functions is not completely understood but species specific mechanisms have been implicated. In this study we have investigated the mechanisms for rat MSC mediated inhibition of T lymphocyte proliferation and secretion of inflammatory cytokines in response to allogeneic and mitogenic stimuli in vitro. MSC inhibited the proliferation of T cells in allogeneic mixed lymphocyte reactions and in response to mitogen with similar efficacy. The anti-proliferative effect was mediated by the induced expression of nitric oxide (NO) synthase and production of NO by MSC. This pathway was required and sufficient to fully suppress lymphocyte proliferation and depended on proximity of MSC and target cells. Expression of inducible NO synthase by MSC was induced through synergistic stimulation with tumor necrosis factor α and interferon γ secreted by activated lymphocytes. Conversely, MSC had a pronounced inhibitory effect on the secretion of these cytokines by T cells which did not depend on NO synthase activity or cell contact, but was partially reversed by addition of the cyclooxygenase (COX) inhibitor indomethacin. In conclusion, rat MSC use different mechanisms to inhibit proliferative and inflammatory responses of activated T cells. While proliferation is suppressed by production of NO, cytokine secretion appears to be impaired at least in part by COX-dependent production of prostaglandin E2

On the Finite Dimensional Laws of Threshold GARCH Processes

In this chapter we establish bounds for the finite dimensional laws of a threshold GARCH process, X, with generating process Z. In this class of models the conditional standard deviation has different reactions according to the sign of past values of the process. So, we firstly find lower and upper bounds for the law of \left ({X}_{1}^{+},-{X}_{1}^{+},\ldots,{X}_{n}^{+},-{X}_{n}^{+}\right), in certain regions of R^{2n}, and use them to find bounds of the law of \left ({X}_{1},\ldots,{X}_{n}\right). Some of these bounds only depend on the parameters of the model and on the distribution function of the independent generating process, Z. An application of these bounds to control charts for time series is presented

Local formation of nitrogen-vacancy centers in diamond by swift heavy ions

We exposed nitrogen-implanted diamonds to beams of swift uranium and gold ions (~1 GeV) and find that these irradiations lead directly to the formation of nitrogen vacancy (NV) centers, without thermal annealing. We compare the photoluminescence intensities of swift heavy ion activated NV- centers to those formed by irradiation with low-energy electrons and by thermal annealing. NV- yields from irradiations with swift heavy ions are 0.1 of yields from low energy electrons and 0.02 of yields from thermal annealing. We discuss possible mechanisms of NV-center formation by swift heavy ions such as electronic excitations and thermal spikes. While forming NV centers with low efficiency, swift heavy ions enable the formation of three dimensional NV- assemblies over relatively large distances of tens of micrometers. Further, our results show that NV-center formation is a local probe of (partial) lattice damage relaxation induced by electronic excitations from swift heavy ions in diamond.Comment: to be published in Journal of Applied Physic