176 research outputs found

    A Robust Initialization Scheme for a Lateral Trajectory Optimization Problem with Time of Arrival Windows

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    We present a robust initialization scheme that estimates parameter values for the numerical solution of a two-point boundary value problem. The two-point boundary value problem formulation stems from the optimization of a cost functional subject to the dynamics of a simplified lateral aircraft model and other constraints. Leveraging regular perturbation methods, initial parameter estimates are analytically determined and used to initialize a gradient descent optimization routine which is shown to rapidly converge over a range of initial aircraft positions and heading angles. Additionally, the velocity of the aircraft is optimized to ensure the trajectory of the aircraft terminates within a desired region in both time and space

    Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load

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    Adaptation to mechanical load, leading to enhanced force and power output, is a characteristic feature of skeletal muscle. Formation of new myonuclei required for efficient muscle hypertrophy relies on prior activation and proliferation of muscle stem cells (MuSCs). However, the mechanisms controlling MuSC expansion under conditions of increased load are not fully understood. Here we demonstrate that interstitial mesenchymal progenitors respond to mechanical load and stimulate MuSC proliferation in a surgical mouse model of increased muscle load. Mechanistically, transcriptional activation of Yes-associated protein 1 (Yap1)/transcriptional coactivator with PDZ-binding motif (Taz) in mesenchymal progenitors results in local production of thrombospondin-1 (Thbs1), which, in turn, drives MuSC proliferation through CD47 signaling. Under homeostatic conditions, however, CD47 signaling is insufficient to promote MuSC proliferation and instead depends on prior downregulation of the Calcitonin receptor. Our results suggest that relayed signaling between mesenchymal progenitors and MuSCs through a Yap1/Taz-Thbs1-CD47 pathway is critical to establish the supply of MuSCs during muscle hypertrophy

    High Yield Production Process for Shigella Outer Membrane Particles

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    Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, outer membrane proteins, and soluble periplasmic components. These particles have been proposed for use as vaccines but the yield has been problematic. We developed a high yielding production process of genetically derived outer membrane particles from the human pathogen Shigella sonnei. Yields of approximately 100 milligrams of membrane-associated proteins per liter of fermentation were obtained from cultures of S. sonnei ΔtolR ΔgalU at optical densities of 30–45 in a 5 L fermenter. Proteomic analysis of the purified particles showed the preparation to primarily contain predicted outer membrane and periplasmic proteins. These were highly immunogenic in mice. The production of these outer membrane particles from high density cultivation of bacteria supports the feasibility of scaling up this approach as an affordable manufacturing process. Furthermore, we demonstrate the feasibility of using this process with other genetic manipulations e.g. abolition of O antigen synthesis and modification of the lipopolysaccharide structure in order to modify the immunogenicity or reactogenicity of the particles. This work provides the basis for a large scale manufacturing process of Generalized Modules of Membrane Antigens (GMMA) for production of vaccines from Gram-negative bacteria

    New CC0\pi\ GENIE Model Tune for MicroBooNE

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    A novel tune has been made for the MicroBooNE experiment. The fit uses 4 new parameters within the GENIE v3.0.6 Monte Carlo program. Charged current pionless data from the T2K experiment was used. New uncertainties were obtained. These results will be used in future MicroBooNE analyses.Comment: 24 pages, 14 figure

    Measurement of neutral current single π0\pi^0 production on argon with the MicroBooNE detector

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    We report the first measurement of π0\pi^0 production in neutral current (NC) interactions on argon with average neutrino energy of 1\lesssim1~GeV. We use data from the MicroBooNE detector's 85-tonne active volume liquid argon time projection chamber situated in Fermilab's Booster Neutrino Beam and exposed to 5.89×10205.89\times10^{20} protons on target for this measurement. Measurements of NC π0\pi^0 events are reported for two exclusive event topologies without charged pions. Those include a topology with two photons from the decay of the π0\pi^0 and one proton and a topology with two photons and zero protons. Flux-averaged cross-sections for each exclusive topology and for their semi-inclusive combination are extracted (efficiency-correcting for two-plus proton final states), and the results are compared to predictions from the \textsc{genie}, \textsc{neut}, and \textsc{NuWro} neutrino event generators. We measure cross sections of 1.243±0.1851.243\pm0.185 (syst) ±0.076\pm0.076 (stat), 0.444±0.098±0.0470.444\pm0.098\pm0.047, and 0.624±0.131±0.0750.624\pm0.131\pm0.075 [1038cm2/Ar][10^{-38}\textrm{cm}^2/\textrm{Ar}] for the semi-inclusive NCπ0\pi^0, exclusive NCπ0\pi^0+1p, and exclusive NCπ0\pi^0+0p processes, respectively.Comment: 16 pages, 14 figures, 2 table
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