The ability of antineutrophil cytoplasm autoantibodies (ANCA) from patients with systemic vasculitis to stimulate protein kinase C (PKC) and tyrosine kinases was examined in human neutrophils. Using the superoxide dismutase-inhibitable reduction of ferricytochrome C, the kinetics of ANCA-induced superoxide (O2-) production were characterized and subsequently manipulated by specific inhibitors of PKC and tyrosine kinases. With this approach, ANCA IgG, but not normal IgG or ANCA F(ab')2 fragments caused a time and dose dependent release of O2- from TNF-alpha primed neutrophils. The kinetics of ANCA-induced O2- production showed an initial 10-15 min lag phase compared to the N-formyl-L-methionyl-L-leucyl-L-phenylalanine response, suggesting differences in the signalling pathways recruited by these two stimuli. Inhibitor studies revealed that ANCA-activation involved members of both the Ca2+-dependent and -independent PKC isoforms and also tyrosine kinases. ANCA IgG resulted in the translocation of the betaII isoform of PKC at a time corresponding to the end of the lag phase of O2- production, suggesting that PKC activity may be instrumental in processes regulating the activity of the NADPH oxidase in response to ANCA. Tyrosine phosphorylation of numerous proteins also peaked 10-15 min after stimulation with ANCA but not normal IgG. These data suggest that PKC and tyrosine kinases regulate O2- production from neutrophils stimulated with autoantibodies from patients with systemic vasculitis.
A Lagrangian finite element algorithm is described for solving two-dimensional, timedependent free surface fluid flows such as those that occur in industrial printing processes. The algorithm is applied using a problem specific structured meshing strategy, implemented with periodic remeshing to control element distortion. The method is benchmarked on the problem of a stretching filament of viscous liquid, which clearly demonstrates the applicability of the approach to flows involving substantial free surface deformation. The model printing problem of the transfer of Newtonian liquid from an upturned trapezoidal trench (3-D cavity with a large transverse aspect ratio) to a horizontal substrate, which is pulled perpendicularly downwards from the cavity, is solved computationally using the Lagrangian scheme. The idealized 2-D liquid motion is tracked from start-up to the point where a thin sheet forms -connecting the liquid remaining in the cavity to a "sessile" drop on the moving substrate. The effect of varying substrate separation speed is briefly discussed and predictions are made for approximate drop volumes and "limiting" domain lengths.
Methods for assembling crossbars from nanowires (NWs) have been designed and implemented. Methods for controlling individual NWs within a crossbar have also been proposed, but implementation remains a challenge. A NW decoder is a device that controls many NWs with a much smaller number of lithographically produced mesoscale wires (MWs). Unlike traditional demultiplexers, all proposed NW decoders are assembled stochastically. In a randomized-contact decoder (RCD) [11], for example, field-effect transistors are randomly created at about half of the NW/MW junctions.In this paper, we tightly bound the number of MWs required to produce a correctly functioning RCD with high probability. We show that the number of MWs is logarithmic in the number of NWs, even when errors occur. We also analyze the overhead associated with controlling a stochastically assembled decoder. As we explain, lithographically-produced control circuitry must store information regarding which MWs control which NWs. This requires more area than the MWs themselves, but has received little attention elsewhere.
The performance of an anti-IgG/A/M and two anti-IgG alkaline phosphatase (AP) conjugates in a commercial antigen capture ELISA (ACE) were compared for their ability to detect antibodies to human platelet antigens (HPAs) contained in 11 sera. Three anti-HPA-1a and one anti-HPA-3a were not detected by the anti-IgG/A/M conjugate, but both anti-IgG conjugates detected all HPA antibodies as a consequence of increased sensitivity in detecting specific antibody binding. This increase varied from 10% to 500%, depending on the serum being tested. The increased sensitivity in some instances was also accompanied by an apparent increase in nonspecific binding, as measured by activity against irrelevant glycoproteins that should not have been recognized by the relevant HPA antibodies in the sera in question. Hence, anti-IgG conjugates would appear to be preferable for detecting platelet-reactive antibodies in many clinical situations; however, the choice of anti-IgG conjugate should be made judiciously (and appropriately validated), in order to avoid false positive results arising from increased nonspecific binding, which may otherwise be erroneously attributed to the presence of auto-antibodies in the serum under investigation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.