SummaryWe have previously demonstrated that human peripheral blood low density mononuclear cells cultured in granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 develop into dendritic cells (DCs) that are extremely efficient in presenting soluble antigens to T ceils. To identify the mechanisms responsible for efficient antigen capture, we studied the endocytic capacity of DCs using fluorescein isothiocyanate--dextran, horseradish peroxidase, and lucifer yellow. We found that DCs use two distinct mechanisms for antigen capture. The first is a high level of fluid phase uptake via macropinocytosis. In contrast to what has been found with other cell types, macropinocytosis in DCs is constitutive and allows continuous internalization of large volumes of fluid. The second mechanism of capture is mediated via the mannose receptor (MR), which is expressed at high levels on DCs. At low ligand concentrations, the MR can deliver a large number of ligands to the cell in successive rounds. Thus, while macropinocytosis endows DCs with a high capacity, nonsaturable mechanism for capture of any soluble antigen, the MR gives an extra capacity for antigen capture with some degree of selectivity for non-self molecules. In addition to their high endocytic capacity, DCs from GM-CSF+ IL-4-dependent cultures are characterized by the presence of a large intracellular compartment that contains high levels of class II molecules, cathepsin D, and lysosomal-~issociated membrane protein-I, and is rapidly accessible to endocytic markers. We investigated whether the capacity of DCs to capture and process antigen could be modulated by exogenous stimuli. We found that DCs respond to tumor necrosis factor or, CD40 ligand, IL-1, and lipopolysaccharide with a coordinate series of changes that include downregulation of macropinocytosis and Fc receptors, disappearance of the class II compartment, and upregulation of adhesion and costimulatory molecules. These changes occur within 1-2 d and are irreversible, since neither pinocytosis nor the class II compartment are recovered when the maturation-inducing stimulus is removed. The specificity of the MR and the capacity to respond to inflammatory stimuli maximize the capacity of DCs to present infectious non-self antigens to T cells.
Flatband networks are characterized by the coexistence of dispersive and flatbands. Flatbands (FBs) are generated by compact localized eigenstates (CLSs) with local network symmetries, based on destructive interference. Correlated disorder and quasiperiodic potentials hybridize CLSs without additional renormalization, yet with surprising consequences: (i) states are expelled from the FB energy E_{FB}, (ii) the localization length of eigenstates vanishes as ξ∼1/ln(E-E_{FB}), (iii) the density of states diverges logarithmically (particle-hole symmetry) and algebraically (no particle-hole symmetry), and (iv) mobility edge curves show algebraic singularities at E_{FB}. Our analytical results are based on perturbative expansions of the CLSs and supported by numerical data in one and two lattice dimensions.
The equilibrium value of an observable defines a manifold in the phase space of an ergodic and equipartitioned many-body system. A typical trajectory pierces that manifold infinitely often as time goes to infinity. We use these piercings to measure both the relaxation time of the lowest frequency eigenmode of the Fermi-Pasta-Ulam chain (FPU), as well as the fluctuations of the subsequent dynamics in equilibrium. The dynamics in equilibrium is characterized by a power-law distribution of excursion times far off equilibrium, with diverging variance. Long excursions arise from sticky dynamics close to q-breathers localized in normal mode space. Measuring the exponent allows to predict the transition into nonergodic dynamics. We generalize our method to Klein-Gordon lattices (KG) where the sticky dynamics is due to discrete breathers localized in real space.Equipartition and thermalization have been central research topics in many-body interacting systems since the time of Maxwell, Boltzmann and Gibbs. The first computer experiment, aimed to observe equipartition starting from a microscopic reversible dynamical system, was carried out in the 1950s by Enrico Fermi, John Pasta, Stanislaw Ulam and Mary Tsingou [1]. Now famous as the Fermi-Pasta-Ulam (FPU) paradox (for reviews see [2][3][4][5]), this experiment failed to find equipartition but instead revealed intriguing nonlinear dynamics -including the celebrated FPU recurrences [1] -which has challenged and puzzled researchers for more than 60 years (for a recent survey of the state of the art, see [4]). In brief, attempts to understand the full dynamics, including the recurrences, led to the observation (and naming) of solitons [6,7] and important developments in Hamiltonian chaos [8]. It is now known that these unexpected recurrences are linked to the choice of initial conditions used by FPU, which are set close to exact coherent time-periodic (or even quasiperiodic) trajectories, e.g. q-breathers, which show exponential localization of energy in normal mode space [9,10]. Even if these trajectories have support of measure zero in the phase space, they might have a finite measure impact simply by being linearly stable [9]. Several other studies admit coherent time-periodic states localized in real space, which are known as discrete breathers or intrinsic localized modes [11] and exist e.g. in Klein-Gordon (KG) lattices [12]. These states can also be linearly stable and thus may have finite measure impact. Importantly, both discrete breathers and q-breathers have been experimentally observed in a large variety of physical settings [11,13]. Thus the central question becomes: How does the presence of such coherent states of measure zero affect the dynamical properties of a thermalized many-body system? How do they affect the possible transition from ergodic to a non-ergodic dynamics? Interestingly there are only a few recorded numerical attempts to address this complex issue [14][15][16][17][18][19][20][21]. In our view, this is the result of the lack of a clear strate...
The microcanonical Gross-Pitaevskii (also known as the semiclassical Bose-Hubbard) lattice model dynamics is characterized by a pair of energy and norm densities. The grand canonical Gibbs distribution fails to describe a part of the density space, due to the boundedness of its kinetic energy spectrum. We define Poincaré equilibrium manifolds and compute the statistics of microcanonical excursion times off them. The tails of the distribution functions quantify the proximity of the many-body dynamics to a weakly nonergodic phase, which occurs when the average excursion time is infinite. We find that a crossover to weakly nonergodic dynamics takes place inside the non-Gibbs phase, being unnoticed by the largest Lyapunov exponent. In the ergodic part of the non-Gibbs phase, the Gibbs distribution should be replaced by an unknown modified one. We relate our findings to the corresponding integrable limit, close to which the actions are interacting through a short range coupling network.
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