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Search processes often involve multiple agents that collectively look for a randomly located target. While increasing the number of agents usually decreases the time at which the first agent finds the target, it also requires resources to create and sustain more agents. In this letter, we consider a collective search cost that not only accounts for the search time but also for the cost associated to the creation and the maintenance of an agent. We first present a general formalism for independent agents in terms of the survival probability of the target for a single-agent search s(t), where we allow agents to be introduced in the system one after the other. From this, we first derive analytically the optimal number of searchers to launch initially in the system. Then, we identify the optimal strategies for exponential and algebraic single-agent survival probabilities by pointing out the ideal times at which new searchers should be launched in the system. Our results show that all searchers should be launched simultaneously in the exponential case, while some should be launched at later times in the algebraic case. Finally, we compare these results with numerical simulations of a strongly interacting collective search, the true self-avoiding walk, and show how the optimal strategy differ from the non-interacting case.

We undertake a numerical study of the ordering kinetics in the two-dimensional (2d) active Ising model (AIM), a discrete flocking model with a non-conserved scalar order parameter. We find that for a quench into the liquid-gas coexistence region and in the ordered liquid region, the characteristic length scale of both the density and magnetization domains follows the Lifshitz-Cahn-Allen (LCA) growth law: R(t)∼t1/2, consistent with the growth law of passive systems with scalar order parameter and non-conserved dynamics. The system morphology is analyzed with the two-point correlation function and its Fourier transform, the structure factor, which conforms to the well-known Porod's law, a manifestation of the coarsening of compact domains with smooth boundaries. We also find the domain growth exponent unaffected by different noise strengths and self-propulsion velocities of the active particles. However, transverse diffusion is found to play the most significant role in the growth kinetics of the AIM. We extract the same growth exponent by solving the hydrodynamic equations of the AIM.

We numerically study a discretized Vicsek model (DVM) with particles orienting in q possible orientations in two dimensions. The study probes the significance of anisotropic orientation and microscopic interaction on the macroscopic behavior. The DVM is an off-lattice flocking model like the active clock model [ACM; EPL {\bf 138}, 41001 (2022)] but the dynamical rules of particle alignment and movement are inspired by the prototypical Vicsek model (VM). The DVM shows qualitatively similar properties as the ACM for intermediate noise strength where a transition from macrophase to microphase separation of the coexistence region is observed as q is increased. But for small q and noise strength, the liquid phase appearing in the ACM at low temperatures is replaced in the DVM by a configuration of multiple clusters with different polarization which does not exhibit any long-range order. We find that the dynamical rules have a profound influence on the overarching features of the flocking phase. We further identify the metastability of the ordered liquid phase subjected to a perturbation.

We numerically study a discretized Vicsek model (DVM) with particles orienting in q possible orientations in two dimensions. The study investigates the significance of anisotropic orientation and microscopic interaction on macroscopic behavior. The DVM is an off-lattice flocking model like the active clock model (ACM; Chatterjee et al 2022 Europhys. Lett.138 41001) but the dynamical rules of particle alignment and movement are inspired by the prototypical Vicsek model (VM). The DVM shows qualitatively similar properties as the ACM for intermediate noise strength where a transition from macrophase to microphase separation of the coexistence region is observed as q is increased. But for small q and noise strength, the liquid phase appearing in the ACM at low temperatures is replaced in the DVM by a configuration of multiple clusters with different polarizations, which does not exhibit any long-range order. We find that the dynamical rules have a profound influence on the overarching features of the flocking phase. We further identify the metastability of the ordered liquid phase subjected to a perturbation.

Many biological active agents respond to gradients of environmental cues by redirecting their motion. In addition to the well-studied prominent examples such as phototaxis and chemotaxis, there has been considerable recent interest in topotaxis, i.e., the ability to sense and follow topographic environmental cues. A trivial topotaxis is achievable through a spatial gradient of obstacle density, though over limited length scales. Here, we introduce a type of topotaxis based on sliding of particles along obstacles—as observed, e.g., in bacterial dynamics near surfaces. We numerically demonstrate how imposing a gradient in the angle of sliding along pillars breaks the spatial symmetry and biases the direction of motion, resulting in an efficient topotaxis in a uniform pillar park. By repeating blocks of pillars with a strong gradient of sliding angle, we propose an efficient method for guiding particles over arbitrary long distances. We provide an explanation for this spectacular phenomenon based on effective reflection at the borders of neighboring blocks. Our results are of technological and medical importance for design of efficient taxis devices for living agents.

An important challenge in active matter lies in harnessing useful global work from entities that produce work locally, e.g., via self-propulsion. We investigate here the active matter version of a classical capillary rise effect, by considering a non-phase separated sediment of self-propelled Janus colloids in contact with a vertical wall. We provide experimental evidence of an unexpected and dynamic adsorption layer at the wall. Additionally, we develop a complementary numerical model that recapitulates the experimental observations. We show that an adhesive and aligning wall enhances the pre-existing polarity heterogeneity within the bulk, enabling polar active particles to climb up a wall against gravity, effectively powering a global flux. Such steady-state flux has no equivalent in a passive wetting layer.

Agents searching for a target can improve their efficiency by memorizing where they have already been searching or by cooperating with other searchers and using strategies that benefit from collective effects. This chapter reviews such concepts: non-Markovian and collective search strategies. We start with the first passage properties of continuous non-Markovian processes and then proceed to the discrete random walker with 1-step and n-step memory. Next we discuss the auto-chemotactic walker, a random walker that produces a diffusive chemotactic cue from which the walker tries to avoid. Then ensembles of agents searching for a single target are discussed, whence the search efficiency may comprise in addition to the first passage time also metabolic costs. We consider the first passage properties of ensembles of chemotactic random walkers and then the pursuit problem, in which searchers (or hunters / predators) see the mobile target over a certain distance. Evasion strategies of single or many targets are also elucidated. Finally we review collective foraging strategies comprising many searchers and many immobile targets. We finish with an outlook on future research directions comprising yet unexplored search strategies of immune cells and in swarm robotics.

The double-well Bose Hubbard model with nearest-neighbor and cavitymediated long-range interactions
(2023)

We consider a one-dimensional Bose-Hubbard model (BHM) with on-site double-well potentials and study the effect of nearest-neighbor repulsion and cavity-mediated long-range interactions by calculating the ground-state phase diagrams with quantum Monte-Carlo simulations. We show that when the intra-well repulsion is as strong as the on-site repulsion a dimerized Mott insulator phase appears at the tip of the dimerized Density Wave phase for a density of one particle per double well. Furthermore, we find a dimerized Haldane insulator phase in the double-well BHM with nearest-neighbor interaction, which is identical to a dimerized BHM with repulsive interactions up to the third neighbor.

We study interacting active Brownian particles (ABPs) with a space-dependent swim velocity via simulation and theory. We find that, although an equation of state exists, a mechanical equilibrium does not apply to ABPs in activity landscapes. The pressure difference originates in the flux of polar order and the gradient of swim velocity across the interface between regions of different activity. In contrast to motility-induced phase separation of ABPs with a homogeneous swim velocity, a critical point does not exist for an active-passive patch system, which continuously splits into a dense and a dilute phase with increasing activity. However, if the global density is so high that not all particles can be packed onto the inactive patch, then MIPS-like behavior is restored and the pressure is balanced again.

Recently it was predicted, on the basis of a lattice gas model, that scalar active matter in a gravitational field would rise against gravity up a confining wall or inside a thin capillary - in spite of repulsive particle-wall interactions [Phys. Rev. Lett. 124, 048001 (2020)]. In this paper we confirm this prediction with sedimenting active Brownian particles (ABPs) in a box and elucidate the mechanism leading to the formation of a meniscus rising above the bulk of the sedimentation region. The height of the meniscus increases with the activity of the system, algebraically with the Péclet number. The formation of the meniscus is determined by a stationary circular particle current, a vortex, centered at the base of the meniscus, whose size and strength increases with the ABP activity. The origin of these vortices can be traced back to the confinement of the ABPs in a box: already the stationary state of ideal (non-interacting) ABPs without gravitation displays circular currents that arrange in a highly symmetric way in the eight octants of the box. Gravitation distorts this vortex configuration downward, leaving two major vortices at the two side walls, with a strong downward flow along the walls. Repulsive interactions between the ABPs change this situation only as soon as motility induced phase separation (MIPS) sets in and forms a dense, sedimented liquid region at the bottom, which pushes the center of the vortex upwards towards the liquid-gas interface. Self-propelled particles therefore represent an impressive realization of scalar active matter that forms stationary particle currents being able to perform visible work against gravity or any other external field, which we predict to be observable experimentally in active colloids under gravitation.

We investigate the phase transitions of the q-state Brownian Potts model in two dimensions (2d) comprising Potts spins that diffuse like Brownian particles and interact ferromagnetically with other spins within a fixed distance. With extensive Monte Carlo simulations we find a continuous phase transition from a paramagnetic to a ferromagnetic phase even for q>4. This is in sharp contrast to the existence of a discontinuous phase transition in the equilibrium q-state Potts model in 2d with q>4. We present detailed numerical evidence for a continuous phase transition and argue that diffusion generated dynamical positional disorder suppresses phase coexistence leading to a continuous transition.

Many biological active agents respond to gradients of environmental cues by redirecting their motion. Besides the well-studied prominent examples such as photo- and chemotaxis, there has been considerable recent interest in topotaxis, i.e.\ the ability to sense and follow topographic environmental cues. We numerically investigate the topotaxis of active agents moving in regular arrays of circular pillars. While a trivial topotaxis is achievable through a spatial gradient of obstacle density, here we show that imposing a gradient in the characteristics of agent-obstacle interaction can lead to an effective topotaxis in an environment with a spatially uniform density of obstacles. As a proof of concept, we demonstrate how a gradient in the angle of sliding around pillars -- as e.g.\ observed in bacterial dynamics near surfaces -- breaks the spatial symmetry and biases the direction of motion. We provide an explanation for this phenomenon based on effective reflection at the imaginary interface between pillars with different sliding angles. Our results are of technological importance for design of efficient taxis devices.

Cytotoxic T lymphocytes (CTLs) are involved in development of diabetes. However, the impact of excessive glucose on CTL-mediated antigen-independent killing remains elusive. Here, we report that TNF-related apoptosis inducing ligand (TRAIL) is substantially up- regulated in CTLs in environments with high glucose (HG) both in vitro and in vivo. The PI3K- Akt-NFκB axis and non-mitochondrial reactive oxygen species are essential in HG-induced TRAIL upregulation in CTLs. TRAILhigh CTLs induce apoptosis of pancreatic beta cell line 1.4E7. Metformin and Vitamin D synergistically reduce HG-enhanced expression of TRAIL in CTLs and coherently protect 1.4E7 cells from TRAIL-mediated apoptosis. Notably, in patients with diabetes, correlation between Vitamin D concentrations in plasma and glucose levels is linked to HG-enhanced TRAIL expression on CTLs. Microarray data reveal that OXCT2, an important enzyme in ketone body catabolism, is a promising target in response to vitamin D. Our work not only reveals a novel mechanism of CTL involvement in progression of diabetes, but also establishes CTLs as a target for combined metformin and vitamin D therapy to protect pancreatic beta cells of diabetic patients.Competing Interest StatementThe authors have declared no competing interest.

Visualizing interactions between cells and the extracellular matrix (ECM) mesh is important to understand cell behavior and regulatory mechanisms by the extracellular environment. However, long term visualization of three-dimensional (3D) matrix structures remains challenging mainly due to photobleaching or blind spots perpendicular to the imaging plane. Here, we combine label-free light-sheet scattering microcopy (LSSM) and fluorescence microscopy to solve these problems. We verified that LSSM can reliably visualize structures of collagen matrices from different origin including bovine, human and rat tail. The quality and intensity of collagen structure images acquired by LSSM did not decline with time. LSSM offers abundant wavelength choice to visualize matrix structures, maximizing combination possibilities with fluorescently-labelled cells, allowing visualizing of long-term ECM-cell interactions in 3D. Interestingly, we observed ultrathin thread-like structures between cells and matrix using LSSM, which were not observed by normal fluorescence microscopy. Transient local alignment of matrix by cell-applied forces can be observed. In summary, LSSM provides a powerful and robust approach to investigate the complex interplay between cells and ECM.Competing Interest StatementThe authors have declared no competing interest.

Profiling of cytokines, chemokines and growth factors in saliva and gingival crevicular fluid
(2021)

In saliva and gingival crevicular fluid (GCF) soluble factors such as cytokines, chemokines and growth factors have shown a great potential serving as biomarkers for early detection and/or diagnosis of oral and systemic diseases. However, GCF and saliva, which one is a better source is still under debate. This study aimed to gain an overview of cytokines, chemokines and growth factors in saliva and GCF to pave the way for selecting suitable oral fluids for oral and systemic diseases. Multiplex cytokine assay was conducted to determine concentrations of cytokines, chemokines and growth factors in saliva and GCF samples from healthy subjects. The protocol for sample collection was carefully optimized. Stabilization, repeatability, and donor variation of the profiles were analyzed. We found that for different donors, cytokine and chemokine profiles showed unique patterns in saliva but similar patterns in GCF. In terms of growth factors, the profiles were individualized in saliva and GCF. All profiles stayed stable for the same healthy individual. In saliva, profiles of cytokines, chemokines and growth factors are individualized for different donors. In GCF, profiles of cytokines and chemokines are similar. Other factors, such as growth factors and T helper-related cytokines, are highly variable in donors. Profiles of soluble factors are not correlated in saliva and GCF. The comprehensive cytokine profiles in saliva and GCF reported in this work would serve as a good base for choosing promising cytokines for developing biomarkers in oral fluids.Competing Interest StatementThe authors have declared no competing interest.

T cells are activated by cognate target cells via an intimate contact, termed immunological synapse (IS). Cellular mechanical properties, especially stiffness, are essential to regulate cell functions, T cell stiffness at a subcellular level at the IS still remains largely elusive. In this work, we established an atomic force microscopy (AFM)-based elasticity mapping method on whole T cells to obtain an overview of the stiffness with a resolution of ~ 60 nm. Using Jurkat T-cells and primary human CD4+ T cells, we show that in the T cells in contact with functionalized surfaces, the lamellipodia are stiffer than the cell body. Upon IS formation, T cell stiffness is substantially enhanced both at the lamellipodia and in cell body. Chelation of intracellular Ca2+ abolishes IS-induced stiffening at the lamellipodia but has no influence on cell body-stiffening, suggesting different regulatory mechanism of IS-induced stiffening between the lamellipodia and the cell body.Competing Interest StatementThe authors have declared no competing interest.

Adhesion between an elastic body and a smooth, rigid substrate can lead to large tensile stresses between them. However, most macroscopic objects are microscopically rough, which strongly suppresses adhesion. A fierce debate has unfolded recently as to whether local or global parameters determine the crossover between small and large adhesion. Here, we report simulations revealing that the dependence of the pull-off force Fn on the surface energy γ does not only have two regimes of high and low adhesion but up to four regimes. They are related to contacts, which at the moment of rupture consist of (i) the last individual Hertzian-shaped contact, in which is linear in γ, (ii) a last meso-scale, individual patches with super-linear scaling, (iii) many isolated contact patches with extremely strong scaling, and (iv) a dominating largest contact patch, for which the pull-off stress is no longer negligible compared to the maximum, microscopic pull-off stress. Regime (iii) can be seen as a transition domain. It is located near the point where the surface energy is half the elastic energy per unit area in conformal contact. A criterion for the transition between regimes (i) and (ii) appears difficult to grasp.

We study the effect of long-term habituation signatures of auditory selective attention reflected in the instantaneous phase information of the auditory event-related potentials (ERPs) at four distinct stimuli levels of 60, 70, 80, and 90 dB SPL. The analysis is based on the single-trial level. The effect of habituation can be observed in terms of the changes (jitter) in the instantaneous phase information of ERPs. In particular, the absence of habituation is correlated with a consistently high phase synchronization over ERP trials. We estimate the changes in phase concentration over trials using a Bayesian approach, in which the phase is modeled as being drawn from a von Mises distribution with a concentration parameter which varies smoothly over trials. The smoothness assumption reflects the fact that habituation is a gradual process. We differentiate between different stimuli based on the relative changes and absolute values of the estimated concentration parameter using the proposed Bayesian model.