103 research outputs found

    Three-dimensional Numerical Modeling and Computational Fluid Dynamics Simulations to Analyze and Improve Oxygen Availability in the AMC Bioartificial Liver

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    A numerical model to investigate fluid flow and oxygen (O(2)) transport and consumption in the AMC-Bioartificial Liver (AMC-BAL) was developed and applied to two representative micro models of the AMC-BAL with two different gas capillary patterns, each combined with two proposed hepatocyte distributions. Parameter studies were performed on each configuration to gain insight in fluid flow, shear stress distribution and oxygen availability in the AMC-BAL. We assessed the function of the internal oxygenator, the effect of changes in hepatocyte oxygen consumption parameters in time and the effect of the change from an experimental to a clinical setting. In addition, different methodologies were studied to improve cellular oxygen availability, i.e. external oxygenation of culture medium, culture medium flow rate, culture gas oxygen content (pO(2)) and the number of oxygenation capillaries. Standard operating conditions did not adequately provide all hepatocytes in the AMC-BAL with sufficient oxygen to maintain O(2) consumption at minimally 90% of maximal uptake rate. Cellular oxygen availability was optimized by increasing the number of gas capillaries and pO(2) of the oxygenation gas by a factor two. Pressure drop over the AMC-BAL and maximal shear stresses were low and not considered to be harmful. This information can be used to increase cellular efficiency and may ultimately lead to a more productive AMC-BAL

    IgE and IgG4 epitopes of the peanut allergens shift following oral immunotherapy

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    Background Oral immunotherapy (OIT) with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Aimmune Therapeutics) is an FDA-approved treatment to desensitize peanut allergic participants. Objective Here we assessed shifts in IgE and IgG4 binding to peanut allergens and their epitopes recognized by United States (US) peanut allergic participants (n = 20) enrolled in phase 3 PTAH OIT clinical trials. Methods Pre- and post- trial participant sera were collected approximately 12 months apart and tested for IgE binding to intact peanut proteins via ImmunoCAP ISAC immunoassays. IgE and IgG4 linear epitopes were identified based on binding to synthetic overlapping 15-mer linear peptides of 10 peanut allergens (Ara h 1-11) synthesized on microarray slides. Results Statistically significant decreases in IgE binding were identified for intact Ara h 2, 3, and 6, and known and newly identified IgE epitopes were shown to exhibit shifts towards IgG4 binding post-OIT, with most linear peptides having increased IgG4 binding after treatment with PTAH. While PTAH does not seem to alter the actual peptide binding patterns significantly after one year of treatment, the IgE and IgG4 binding ratios and intensity are altered. Conclusion At a population level, the linear IgE and IgG4 epitopes of 10 peanut allergens overlap and that increase in IgG4 with OIT results in displacement of IgE binding to both conformational and linear epitopes. Furthermore, it appears as though the increase in IgG4 is more important to achieve desensitization at the 12-month timepoint than the decrease in IgE. This type of knowledge can be useful in the identification of IgE and IgG4-binding allergen and peptide biomarkers that may indicate desensitization or sustained unresponsiveness of allergic individuals to peanut

    Effect of tube diameter and capillary number on platelet margination and near-wall dynamics

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    The effect of tube diameter DD and capillary number CaCa on platelet margination in blood flow at 37%\approx 37\% tube haematocrit is investigated. The system is modelled as three-dimensional suspension of deformable red blood cells and nearly rigid platelets using a combination of the lattice-Boltzmann, immersed boundary and finite element methods. Results show that margination is facilitated by a non-diffusive radial platelet transport. This effect is important near the edge of the cell-free layer, but it is only observed for Ca>0.2Ca > 0.2, when red blood cells are tank-treading rather than tumbling. It is also shown that platelet trapping in the cell-free layer is reversible for Ca0.2Ca \leq 0.2. Only for the smallest investigated tube (D=10μmD = 10 \mu\text{m}) margination is essentially independent of CaCa. Once platelets have reached the cell-free layer, they tend to slide rather than tumble. The tumbling rate is essentially independent of CaCa but increases with DD. Tumbling is suppressed by the strong confinement due to the relatively small cell-free layer thickness at 37%\approx 37\% tube haematocrit.Comment: 16 pages, 10 figure

    Hierarchy of Scales in Language Dynamics

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    Methods and insights from statistical physics are finding an increasing variety of applications where one seeks to understand the emergent properties of a complex interacting system. One such area concerns the dynamics of language at a variety of levels of description, from the behaviour of individual agents learning simple artificial languages from each other, up to changes in the structure of languages shared by large groups of speakers over historical timescales. In this Colloquium, we survey a hierarchy of scales at which language and linguistic behaviour can be described, along with the main progress in understanding that has been made at each of them − much of which has come from the statistical physics community. We argue that future developments may arise by linking the different levels of the hierarchy together in a more coherent fashion, in particular where this allows more effective use of rich empirical data sets

    The CLAS12 Spectrometer at Jefferson Laboratory

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    The CEBAF Large Acceptance Spectrometer for operation at 12 GeV beam energy (CLAS12) in Hall B at Jefferson Laboratory is used to study electro-induced nuclear and hadronic reactions. This spectrometer provides efficient detection of charged and neutral particles over a large fraction of the full solid angle. CLAS12 has been part of the energy-doubling project of Jefferson Lab's Continuous Electron Beam Accelerator Facility, funded by the United States Department of Energy. An international collaboration of 48 institutions contributed to the design and construction of detector hardware, developed the software packages for the simulation of complex event patterns, and commissioned the detector systems. CLAS12 is based on a dual-magnet system with a superconducting torus magnet that provides a largely azimuthal field distribution that covers the forward polar angle range up to 35∘, and a solenoid magnet and detector covering the polar angles from 35° to 125° with full azimuthal coverage. Trajectory reconstruction in the forward direction using drift chambers and in the central direction using a vertex tracker results in momentum resolutions of <1% and <3%, respectively. Cherenkov counters, time-of-flight scintillators, and electromagnetic calorimeters provide good particle identification. Fast triggering and high data-acquisition rates allow operation at a luminosity of 1035 cm−2s−1. These capabilities are being used in a broad program to study the structure and interactions of nucleons, nuclei, and mesons, using polarized and unpolarized electron beams and targets for beam energies up to 11 GeV. This paper gives a general description of the design, construction, and performance of CLAS12
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