Natural killer (NK) cells serve as one of the first lines of defense against viral infections and transformed cells. NK cell cytotoxicity is not dependent on antigen presentation by target cells, but is dependent on integration of activating and inhibitory signals triggered by receptor–ligand interactions formed at a tight intercellular contact between the NK and target cell, i.e., the immune synapse. We have studied the single-cell migration behavior and target-cell contact dynamics of resting and interleukin (IL)-2-activated human peripheral blood NK cells. Small populations of NK cells and target cells were confined in microwells and imaged by fluorescence microscopy for >8 h. Only the IL-2-activated population of NK cells showed efficient cytotoxicity against the human embryonic kidney 293T target cells. We found that although the average migration speeds were comparable, activated NK cells showed significantly more dynamic migration behavior, with more frequent transitions between periods of low and high motility. Resting NK cells formed fewer and weaker contacts with target cells, which manifested as shorter conjugation times and in many cases a complete lack of post-conjugation attachment to target cells. Activated NK cells were approximately twice as big as the resting cells, displayed a more migratory phenotype, and were more likely to employ “motile scanning” of the target-cell surface during conjugation. Taken together, our experiments quantify, at the single-cell level, how activation by IL-2 leads to altered NK cell cytotoxicity, migration behavior, and contact dynamics.
Recent experiments demonstrate the importance of substrate curvature for actively forced fluid dynamics. Yet, the covariant formulation and analysis of continuum models for nonequilibrium flows on curved surfaces still poses theoretical challenges. Here, we introduce and study a generalized covariant Navier-Stokes model for fluid flows driven by active stresses in nonplanar geometries. The analytical tractability of the theory is demonstrated through exact stationary solutions for the case of a spherical bubble geometry. Direct numerical simulations reveal a curvature-induced transition from a burst phase to an anomalous turbulent phase that differs distinctly from externally forced classical 2D Kolmogorov turbulence. This new type of active turbulence is characterized by the self-assembly of finite-size vortices into linked chains of antiferromagnetic order, which percolate through the entire fluid domain, forming an active dynamic network. The coherent motion of the vortex chain network provides an efficient mechanism for upward energy transfer from smaller to larger scales, presenting an alternative to the conventional energy cascade in classical 2D turbulence.
Mixed monotone systems form an important class of nonlinear systems that have recently received attention in the abstraction-based control design area. Slightly different definitions exist in the literature, and it remains a challenge to verify mixed monotonicity of a system in general. In this paper, we first clarify the relation between different existing definitions of mixed monotone systems, and then give two sufficient conditions for mixed monotone functions defined on Euclidean space. These sufficient conditions are more general than the ones from the existing control literature, and they suggest that mixed monotonicity is a very generic property. Some discussions are provided on the computational usefulness of the proposed sufficient conditions.
Abstract-This paper considers the problem of synthesizing output-feedback control laws for a class of discrete-time hybrid systems in order for the trajectories of the system to satisfy certain high-level specifications expressed in linear temporal logic. By leveraging ideas from robust interpretation of temporal logic formulas and bounded-error estimation, we identify a subclass of systems for which it is possible to reduce the problem to a state-feedback form. In particular, we use locally superstable hybrid observers to resolve the partial information at the continuous level. This allows us to use recent results in temporal logic planning to synthesize the desired controllers based on two-player perfect-information games. The overall control architecture consists of a hybrid observer, a highlevel switching protocol and a low-level continuous controller. We demonstrate the proposed framework in a case study on designing control protocols for an aircraft air management system.
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