760 research outputs found

    Developing a closed-form cost expression for an (R,s,nQ) policy where the demand process is compound generalized Erlang.

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    We derive a closed-form cost expression for an (R,s,nQ) inventory control policy where all replenishment orders have a constant lead-time, unfilled demand is backlogged and inter-arrival times of order requests are generalized Erlang distributedInventory control; Compound renewal process; Generalized Erlang distribution;

    SImulator of GAlaxy Millimetre/submillimetre Emission (SIGAME): CO emission from massive z=2 main-sequence galaxies

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    We present SIGAME (SImulator of GAlaxy Millimetre/submillimetre Emission), a new numerical code designed to simulate the 12CO rotational line emission spectrum of galaxies. Using sub-grid physics recipes to post-process the outputs of smoothed particle hydrodynamics (SPH) simulations, a molecular gas phase is condensed out of the hot and partly ionized SPH gas. The gas is subjected to far-UV radiation fields and cosmic ray ionization rates which are set to scale with the local star formation rate volume density. Level populations and radiative transport of the CO lines are solved with the 3-D radiative transfer code LIME. We have applied SIGAME to cosmological SPH simulations of three disc galaxies at z=2 with stellar masses in the range ~(0.5-2)x10^11 Msun and star formation rates ~40-140 Msun/yr. Global CO luminosities and line ratios are in agreement with observations of disc galaxies at z~2 up to and including J=3-2 but falling short of the few existing J=5-4 observations. The central 5 kpc regions of our galaxies have CO 3-2/1-0 and 7-6/1-0 brightness temperature ratios of ~0.55-0.65 and ~0.02-0.08, respectively, while further out in the disc the ratios drop to more quiescent values of ~0.5 and <0.01. Global CO-to-H2 conversion (alpha_CO) factors are ~=1.5 Msun*pc^2/(K km s/1), i.e. ~2-3 times below typically adopted values for disc galaxies, and alpha_CO increases with radius, in agreement with observations of nearby galaxies. Adopting a top-heavy Giant Molecular Cloud (GMC) mass spectrum does not significantly change the results. Steepening the GMC density profile leads to higher global line ratios for J_up>=3 and CO-to-H2 conversion factors [~=3.6 Msun*pc^2/(K km/s)].Comment: 28 pages, 20 figures. Accepted for Publication in MNRAS. Substantial revisions from the previous version, including tests with model galaxies similar to the Milky Way. Improved figures and added table

    Migration and maturation of Langerhans cells in skin transplants and explants

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    Larsen, C.P., Steinman, R.M., Witmer-Pack, M.D., Hankins, D.F., Morris, P.J., and Austyn, J.M. Migration and maturation of Langerhans cells in skin transplants and explants. J. Exp. Med. 172: 1483-1493, 1990https://digitalcommons.rockefeller.edu/historical-scientific-reports/1030/thumbnail.jp

    Migration and maturation of langerhans cells in skin transplants and explants

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    The behavior of Langerhans cells (LC) has been examined after skin transplantation and in an organ culture system. Within 24 h (and even within 4 h of culture), LC in epidermal sheets from allografts, isografts, and explants dramatically increased in size and expression of major histocompatibility complex class II molecules, and their numbers were markedly decreased. Using a new procedure, dermal sheets were then examined. By 24 h, cells resembling LC were found close to the epidermal-dermal junction, and by 3 d, they formed cords in dermal lymphatics before leaving the skin. In organ culture, the cells continued to migrate spontaneously into the medium. These observations establish a direct route for migration of LC from the epidermis into the dermis and then out of the skin. These processes are apparently induced by a local inflammatory response, and are independent ofhost-derived mediators. The phenotype ofmigratory cells was then examined by two-color immunocytochemistry and FACS analysis. The majority of migratory leukocytes were Ia+ LC, the remainder comprised Thy-1+, CD3 +, CD4−, CD8− presumptive T cell receptor γ/δ+ dendritic epidermal cells, which clustered with the LC, and a small population of adherent Ia−, FcRII+, CD11a/18+ macrophages. In contrast to the cells remaining within the epidermis of grafted skin at 1 d, the migratory cells were heterogeneous in phenotype, particularly with respect to F4/80, FcRII, and interleukin 2 receptor ot expression, which are useful markers to follow phenotypic maturation of LC. Moreover, cells isolated from the epidermis of grafts at 1 d were more immunostimulatory in the allogeneic mixed leukocyte reaction and oxidative mitogenesis than LC isolated from normal skin, though less potent than spleen cells. The day 1 migratory cells were considerably more immunostimulatory than spleen cells, and day 3-5 migratory cells even more so, suggesting that functional maturation continues in culture. Thus, maturation ofLC commences in the epidermis and continues during migration, but the cells do not need to be fully mature in phenotype or function before they leave the skin. In vivo, the migration of epidermal LC via the dermis into lymphatics and then to the draining nodes, where they have been shown previously to home to T areas, would provide a powerful stimulus for graft rejection

    Simultaneous inhibition of B7 and LFA-1 signaling prevents rejection of discordant neural xenografts in mice lacking CD40L.

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    Transplantation of embryonic human neural tissue can restore dopamine neurotransmission and improve neurological function in patients with Parkinson's disease. Logistical and ethical factors limit the availability of human embryonic allogeneic tissue. Embryonic xenogeneic neural tissue from porcine donors is an alternative form of donor tissue, but effective immunomodulatory techniques are warranted for neural xenotransplantation to become clinically feasible. We transplanted embryonic porcine ventral mesencephalic tissue into the brains of adult untreated C57BL/6 mice, untreated CD40L-/-mice and CD40L-/-mice that received injections of anti-LFA-1, CTLA41g or both compounds. Double-treated CD40L-/-mice had large grafts with high numbers of dopaminergic neurons 4 wk after transplantation. The grafts were completely devoid of lymphocytes, macrophages and activated microglia. Untreated C57BL/6 mice had rejected their grafts. Untreated CD40L-/-mice and CD40L-/-mice treated with monotherapy of anti-LFA-1 or CTLA41g had smaller grafts and more microglial and lymphocytic infiltration than double-treated CD40L-/-mice. We conclude that immunomodulation with concomitant inhibition of LFA-1 and B7 signaling in the perioperative period in CD40L-/-mice prevented the rejection of discordant neural xenografts. The treatment most likely reduced antigen presenting capacity and interfered with the costimulatory signaling needed for T cell activation to occur

    Developments in algorithmic management from an IR-perspective : Denmark

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    The INCODING project studies dynamics in the (co)governance of Algorithmic Management and Artificial Intelligence-techniques from a Comparative Industrial Relations-perspective. By identifying the main challenges for workers and their representatives, it aims to explore how to contribute to Inclusive and Transparent Algorithmic Management. The present stock tacking reports provide an insight on the latest developments in this field in Denmar

    Antigen-specific precursor frequency impacts T cell proliferation, differentiation, and requirement for costimulation

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    After a brief period of antigenic stimulation, T cells become committed to a program of autonomous expansion and differentiation. We investigated the role of antigen-specific T cell precursor frequency as a possible cell-extrinsic factor impacting T cell programming in a model of allogeneic tissue transplantation. Using an adoptive transfer system to incrementally raise the precursor frequency of antigen-specific CD8+ T cells, we found that donor-reactive T cells primed at low frequency exhibited increased cellular division, decreased development of multifunctional effector activity, and an increased requirement for CD28- and CD154-mediated costimulation relative to those primed at high frequency. The results demonstrated that recipients with low CD4+ and CD8+ donor-reactive T cell frequencies exhibited long-term skin graft survival upon CD28/CD154 blockade, whereas simultaneously raising the frequency of CD4+ T cells to ∼0.5% and CD8+ T cells to ∼5% precipitated graft rejection despite CD28/CD154 blockade. Antigenic rechallenge of equal numbers of cells stimulated at high or low frequency revealed that cells retained an imprint of the frequency at which they were primed. These results demonstrate a critical role for initial precursor frequency in determining the CD8+ T cell requirement for CD28- and CD154-mediated costimulatory signals during graft rejection
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