Search

The transient start-up flow solution with slip is a useful tool to verify Computational Fluid Dynamics (CFD) simulations. However, a highly accurate, open-source black box solution does not seem to be available. Our method provides a fast, automated, and rigorously verified open-source implementation that can compute the hydrodynamic eigenmodes of a two-dimensional channel flow beyond the standard floating-point precision. This allows for a very accurate computation of the corresponding Fourier series solution. We prove that all roots are found in all special cases for the general flow problem with different slip lengths on the channel walls. The numerical results confirm analytically derived asymptotic power laws for the leading hydrodynamic eigenmode and the characteristic timescale in the limiting cases of small and large slip. The code repository including test cases is publicly available here https://git.rwth-aachen.de/fricke/start-up-flow, 29 pages, 10 figures, article manuscript

Monocytes are the third most frequent type of leukocytes in humans, linking innate and adaptive immunity and are critical drivers in many inflammatory diseases. Based on the differential expression of surface antigens, three monocytic subpopulations have been suggested in humans and two in rats with varying inflammatory and phenotype characteristics. Potential intervention strategies that aim to manipulate these cells require an in-depth understanding of monocyte behavior under different conditions. However, monocytes are highly sensitive to their specific activation state and expression of surface markers, which can change during cell isolation and purification. Thus, there is an urgent need for an unbiased functional analysis of activation in monocyte subtypes, which is not affected by the isolation procedure. Here, we present a flow cytometry-based protocol for evaluating subset-specific activation and cytokine expression of circulating blood monocytes both in humans and rats using small whole blood samples (50 - 100 μL). In contrast to previously described monocyte isolation and flow cytometry visualization methods, the presented approach virtually leaves monocyte subsets in a resting state or fixes them in their current state and allows for an unbiased functional endpoint analysis without prior cell isolation. This protocol is a comprehensive tool for studying differential monocyte regulation in the inflammatory and allogeneic immune response in vitro and vivo.

Four different numerical approaches are compared for the rise of liquid between two parallel plates. These are an Arbitrary Lagrangian-Eulerian method (OpenFOAM solver interTrackFoam), a geometric volume of fluid code (FS3D), an algebraic volume of fluid method (OpenFOAM solver interFoam), and a level set approach (BoSSS). The first three approaches discretize the bulk equation using a finite volume method while the last one employs an extended discontinuous Galerkin discretization. The results are compared to ODE models which are the classical rise model and an extended model that incorporates a Navier slip boundary condition on the capillary walls and levels at a corrected stationary rise height. All physical parameters are based on common requirements for the initial conditions, short simulation time, and a non-dimensional parameter study. The comparison shows excellent agreement between the different implementations with minor quantitative deviations for the adapted interFoam implementation. While the qualitative agreement between the full solutions of the continuum mechanical approach and the reference model is good, the quantitative comparison is only reasonable, especially for cases with increasing oscillations. Furthermore, reducing the slip length changes the solution qualitatively as oscillations are completely damped in contrast to the solution of the ODE models. To provide reference data for a full continuum simulation of the capillary rise problem, all results are made available online., 38 pages, 17 figures, benchmark data available online

Ras transmits manifold signals from the TCR at various crossroads in the life of a T cell. For example, selection programs in the thymus or the acquisition of a state of hypo-responsiveness known as anergy are just some of the T cell features known to be controlled by TCR-sparked signals that are intracellularly propagated by Ras. These findings raise the question of how Ras can transmit such a variety of signals leading to the shaping of equally many T cell traits. Because Ras proteins transit through endomembrane compartments on their way to the plasma membrane (PM), compartmentalized Ras activation at distinct subcellular sites represents a potential mechanism for signal diversification in TCR signaling. This hypothesis has been nurtured by studies in T cells engineered to overexpress Ras that reported distinct activation of Ras at the PM and Golgi. Contrary to this scenario, we report in this study that activation of endogenous Ras, imaged in live Jurkat T cells using novel affinity probes for Ras-GTP, proceeds only at the PM even upon enforced signal flux through the diacylglycerol/RasGRP1 pathway. Physiological engagement of the TCR at the immunological synapse in primary T cells caused focalized Ras-GTP accumulation also only at the PM. Analysis of palmitoylation-deficient Ras mutants, which are confined to endomembranes, confirmed that the TCR does not activate Ras in that compartment and revealed a critical function for palmitoylation in N-Ras/H-Ras activation. These findings identify the PM as the only site of TCR-driven Ras activation and document that endomembranes are not a signaling platform for Ras in T cells.