189 research outputs found

    Lines Missing Every Random Point

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    We prove that there is, in every direction in Euclidean space, a line that misses every computably random point. We also prove that there exist, in every direction in Euclidean space, arbitrarily long line segments missing every double exponential time random point.Comment: Added a section: "Betting in Doubly Exponential Time.

    Cytotoxic Capacity of IL-15-Stimulated Cytokine-Induced Killer Cells Against Human Acute Myeloid Leukemia and Rhabdomyosarcoma in Humanized Preclinical Mouse Models

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    Allogeneic stem cell transplantation (allo-SCT) has become an important treatment modality for patients with high-risk acute myeloid leukemia (AML) and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD) status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions based on MRD status using IL-15-expanded cytokine-induced killer (CIK) cells may prevent relapse without causing graft-versus-host-disease (GvHD). To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL-2Rγc−, NSG) were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS) cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow followed by liver, lung, spleen, peripheral blood (PB), and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at equal amounts were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells 250 times more CIK than THP-1 cells were needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliable 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells have potent cytotoxic capacity against AML and RMS cells without causing GvHD

    The connection between computability of a nonlinear problem and its linearization: the Hartman-Grobman theorem revisited

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    As one of the seven open problems in the addendum to their 1989 book Computability in Analysis and Physics Pour-El and Richards (1989)[17], Pour-El and Richards asked, "What is the connection between the computability of the original nonlinear operator and the linear operator which results from it?" Yet at present, systematic studies of the issues raised by this question seem to be missing from the literature. In this paper, we study one problem in this direction: the Hartman-Grobman linearization theorem for ordinary differential equations (ODEs). We prove, roughly speaking, that near a hyperbolic equilibrium point x(0) of a nonlinear ODE (x) over dot = f(x), there is a computable homeomorphism H such that H circle phi = L circle H, where phi is the solution to the ODE and L is the solution to its linearization (x) over dot = Df (x(0)) x. (C) 2012 Elsevier B.V. All rights reserved.Fundacao para a Ciencia e a Tecnologia; EU FEDER POCTI/POCI via SQIG - Instituto de Telecomunicacoes through the FCT [PEst-OE/EEI/LA0008/2011

    Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

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    Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

    Multistation intercomparison of column-averaged methane from NDACC and TCCON: impact of dynamical variability

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    Dry-air column-averaged mole fractions of methane (XCH4) retrieved from ground-based solar Fourier transform infrared (FTIR) measurements provide valuable information for satellite validation, evaluation of chemical-transport models, and source-sink-inversions. In this context, Sussmann et al. (2013) have shown that midinfrared (MIR) soundings from the Network for the Detection of Atmospheric Composition Change (NDACC) can be combined with near-infrared (NIR) soundings from the Total Carbon Column Observing Network (TCCON) without the need to apply an overall intercalibration factor. However, in spite of efforts to reduce a priori impact, some residual seasonal biases were identified, and the reasons behind remained unclear. In extension to this previous work, which was based on multiannual quasi-coincident MIR and NIR measurements from the stations Garmisch (47.48° N, 11.06° E, 743 m a.s.l.) and Wollongong (34.41° S, 150.88° E, 30 m a.s.l.), we now investigate upgraded retrievals with longer temporal coverage and include three additional stations (Ny-Ålesund, 78.92° N, 11.93° E, 20 m a.s.l.; Karlsruhe, 49.08° N, 8.43° E, 110 m a.s.l.; Izaña, 28.31° N, 16.45° W, 2.370 m a.s.l.). Our intercomparison results (except for Ny-Ålesund) confirm that there is no overall bias between MIR and NIR XCH4 retrievals, and all MIR and NIR time series reveal a quasi-periodic seasonal bias for all stations, except for Izaña. We find that dynamical variability causes MIR–NIR differences of up to ~ 30 ppb (parts per billion) for Ny-Ålesund, ~ 20 ppb for Wollongong, ~ 18 ppb for Garmisch, and ~ 12 ppb for Karlsruhe. The mechanisms behind this variability are elaborated via two case studies, one dealing with stratospheric subsidence induced by the polar vortex at Ny-Ålesund and the other with a deep stratospheric intrusion event at Garmisch. Smoothing effects caused by the dynamical variability during these events are different for MIR and NIR retrievals depending on the altitude of the perturbation area. MIR retrievals appear to be more realistic in the case of stratospheric subsidence, while NIR retrievals are more accurate in the case of stratosphere–troposphere exchange (STE) in the upper troposphere/lower stratosphere (UTLS) region. About 35% of the FTIR measurement days at Garmisch are impacted by STE, and about 23% of the measurement days at Ny-Ålesund are influenced by polar vortex subsidence. The exclusion of data affected by these dynamical situations resulted in improved agreement of MIR and NIR seasonal cycles for Ny-Ålesund and Garmisch. We found that dynamical variability is a key factor in constraining the accuracy of MIR and NIR seasonal cycles. To mitigate this impact it is necessary to use more realistic a priori profiles that take these dynamical events into account (e.g., via improved models), and/or to improve the FTIR retrievals to achieve a more uniform sensitivity at all altitudes (possibly including profile retrievals for the TCCON data)
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