Linear Response and Fluctuation-Dissipation Relations for Brownian Motion under Resetting.

We consider fluctuation-dissipation relations (FDRs) for a Brownian motion under renewal resetting with arbitrary waiting time distribution between the resetting events. We show that if the distribution of waiting times of the resetting process possesses the second moment, the usual (generalized) FDR and the equivalent generalized Einstein's relation (GER) apply for the response function of the coordinate. If the second moment of waiting times diverges but the first one stays finite, the static susceptibility diverges, the usual FDR breaks down, but the GER still applies. In any of these situations, the fluctuation dissipation relations define the effective temperature of the system which is twice as high as the temperature of the medium in which the Brownian motion takes place.

Heterogeneous Nucleation in Finite-Size Adaptive Dynamical Networks.

Phase transitions in equilibrium and nonequilibrium systems play a major role in the natural sciences. In dynamical networks, phase transitions organize qualitative changes in the collective behavior of coupled dynamical units. Adaptive dynamical networks feature a connectivity structure that changes over time, coevolving with the nodes' dynamical state. In this Letter, we show the emergence of two distinct first-order nonequilibrium phase transitions in a finite-size adaptive network of heterogeneous phase oscillators. Depending on the nature of defects in the internal frequency distribution, we observe either an abrupt single-step transition to full synchronization or a more gradual multistep transition. This observation has a striking resemblance to heterogeneous nucleation. We develop a mean-field approach to study the interplay between adaptivity and nodal heterogeneity and describe the dynamics of multicluster states and their role in determining the character of the phase transition. Our work provides a theoretical framework for studying the interplay between adaptivity and nodal heterogeneity.

Synchronization transitions in Kuramoto networks with higher-mode interaction.

Synchronization is an omnipresent collective phenomenon in nature and technology, whose understanding is still elusive for real-world systems in particular. We study the synchronization transition in a phase oscillator system with two nonvanishing Fourier-modes in the interaction function, hence going beyond the Kuramoto paradigm. We show that the transition scenarios crucially depend on the interplay of the two coupling modes. We describe the multistability induced by the presence of a second coupling mode. By extending the collective coordinate approach, we describe the emergence of various states observed in the transition from incoherence to coherence. Remarkably, our analysis suggests that, in essence, the two-mode coupling gives rise to states characterized by two independent but interacting groups of oscillators. We believe that these findings will stimulate future research on dynamical systems, including complex interaction functions beyond the Kuramoto-type.

Towards the Use of Individual Fluorescent Nanoparticles as Ratiometric Sensors: Spectral Robustness of Ultrabright Nanoporous Silica Nanoparticles.

Here we address an important roadblock that prevents the use of bright fluorescent nanoparticles as individual ratiometric sensors: the possible variation of fluorescence spectra between individual nanoparticles. Ratiometric measurements using florescent dyes have shown their utility in measuring the spatial distribution of temperature, acidity, and concentration of various ions. However, the dyes have a serious limitation in their use as sensors; namely, their fluorescent spectra can change due to interactions with the surrounding dye. Encapsulation of the d, e in a porous material can solve this issue. Recently, we demonstrated the use of ultrabright nanoporous silica nanoparticles (UNSNP) to measure temperature and acidity. The particles have at least two kinds of encapsulated dyes. Ultrahigh brightness of the particles allows measuring of the signal of interest at the single particle level. However, it raises the problem of spectral variation between particles, which is impossible to control at the nanoscale. Here, we study spectral variations between the UNSNP which have two different encapsulated dyes: rhodamine R6G and RB. The dyes can be used to measure temperature. We synthesized these particles using three different ratios of the dyes. We measured the spectra of individual nanoparticles and compared them with simulations. We observed a rather small variation of fluorescence spectra between individual UNSNP, and the spectra were in very good agreement with the results of our simulations. Thus, one can conclude that individual UNSNP can be used as effective ratiometric sensors.

At Least 10-fold Higher Lubricity of Molecularly Thin D2O vs H2O Films at Single-Layer Graphene-Mica Interfaces.

Interfacial water is a widespread lubricant down to the nanometer scale. We investigate the lubricities of molecularly thin H2O and D2O films confined between mica and graphene, via the relaxation of initially applied strain in graphene employing Raman spectroscopy. Surprisingly, the D2O films are at least 1 order of magnitude more lubricant than H2O films, despite the similar bulk viscosities of the two liquids. We propose a mechanism based on the known selective permeation of protons vs deuterons through graphene. Permeated protons and left behind hydroxides may form ion pairs clamping across the graphene sheet and thereby hindering the graphene from sliding on the water layer. This explains the lower lubricity but also the hindering diffusivity of the water layer, which yields a high effective viscosity in accordance with findings in dewetting experiments. Our work elucidates an unexpected effect and provides clues to the behavior of graphene on hydrous surfaces.

Finite-time recurrence analysis of chaotic trajectories in Hamiltonian systems.

In this work, we show that a finite-time recurrence analysis of different chaotic trajectories in two-dimensional non-linear Hamiltonian systems provides useful prior knowledge of their dynamical behavior. By defining an ensemble of initial conditions, evolving them until a given maximum iteration time, and computing the recurrence rate of each orbit, it is possible to find particular trajectories that widely differ from the average behavior. We show that orbits with high recurrence rates are the ones that experience stickiness, being dynamically trapped in specific regions of the phase space. We analyze three different non-linear maps and present our numerical observations considering particular features in each of them. We propose the described approach as a method to visually illustrate and characterize regions in phase space with distinct dynamical behaviors.

A comparison of methods to assess cell mechanical properties.

The mechanical properties of cells influence their cellular and subcellular functions, including cell adhesion, migration, polarization, and differentiation, as well as organelle organization and trafficking inside the cytoplasm. Yet reported values of cell stiffness and viscosity vary substantially, which suggests differences in how the results of different methods are obtained or analyzed by different groups. To address this issue and illustrate the complementarity of certain approaches, here we present, analyze, and critically compare measurements obtained by means of some of the most widely used methods for cell mechanics: atomic force microscopy, magnetic twisting cytometry, particle-tracking microrheology, parallel-plate rheometry, cell monolayer rheology, and optical stretching. These measurements highlight how elastic and viscous moduli of MCF-7 breast cancer cells can vary 1,000-fold and 100-fold, respectively. We discuss the sources of these variations, including the level of applied mechanical stress, the rate of deformation, the geometry of the probe, the location probed in the cell, and the extracellular microenvironment.

Convergence to a Gaussian by Narrowing of Central Peak in Brownian yet Non-Gaussian Diffusion in Disordered Environments.

In usual diffusion, the concentration profile, starting from an initial distribution showing sharp features, first gets smooth and then converges to a Gaussian. By considering several examples, we show that the art of convergence to a Gaussian in diffusion in disordered media with infinite contrast may be strikingly different: sharp features of initial distribution do not smooth out at long times. This peculiarity of the strong disorder may be of importance for diagnostics of disorder in complex, e.g., biological, systems.

Non-steady-state photo-EMF in ß-Ga2O3 crystals at λ = 457 nm.

The non-steady-state photoelectromotive force is excited in a monoclinic gallium oxide crystal at wavelength λ = 457 nm. The crystal grown in an oxygen atmosphere is insulating and highly transparent for a visible light, nevertheless, the formation of dynamic space-charge gratings and observation of the photo-EMF signal is achieved without application of any electric field to the sample. The dependencies of the signal amplitude on the frequency of phase modulation, light intensity, spatial frequency and light polarization are measured. The material demonstrates the anisotropy along the [100] and [010] directions, namely, there is a small difference in the transport parameters and a pronounced polarization dependence of the signal. The crystal's photoconductivity, responsivity and diffusion length of electrons are estimated for the chosen light wavelength and compared with the ones for other wide-bandgap crystals.

Modeling Echo Chambers and Polarization Dynamics in Social Networks.

Echo chambers and opinion polarization recently quantified in several sociopolitical contexts and across different social media raise concerns on their potential impact on the spread of misinformation and on the openness of debates. Despite increasing efforts, the dynamics leading to the emergence of these phenomena remain unclear. We propose a model that introduces the dynamics of radicalization as a reinforcing mechanism driving the evolution to extreme opinions from moderate initial conditions. Inspired by empirical findings on social interaction dynamics, we consider agents characterized by heterogeneous activities and homophily. We show that the transition between a global consensus and emerging radicalized states is mostly governed by social influence and by the controversialness of the topic discussed. Compared with empirical data of polarized debates on Twitter, the model qualitatively reproduces the observed relation between users' engagement and opinions, as well as opinion segregation in the interaction network. Our findings shed light on the mechanisms that may lie at the core of the emergence of echo chambers and polarization in social media.

Locally temperature - driven mathematical model of West Nile virus spread in Germany.

West Nile virus (WNV) is an arthropod-borne virus (arbovirus) transmitted by the bites of infected mosquitoes. WNV can also infect horses and humans, where it may cause serious illness and can be fatal. Birds are the natural reservoir, and humans, equines and probably other mammals are dead-end hosts. In 2018, WNV occurred for the first time in Germany, affecting birds and horses. Seroconversion of an exposed veterinarian has also been reported. It is therefore of importance to evaluate the circumstances, under which WNV may establish in Germany as a whole or in particular favourable regions. In our current work, we formulate a dynamic model to describe the spreading process of West Nile virus in the presence of migratory birds. To investigate the possible role of migratory birds in the dissemination of WNV in Germany, we include the recurring presence of migratory birds through a mechanistic ordinary differential equations (ODE) model system. We also perform a sensitivity analysis of the infection curves. Seasonal impacts are also taken into consideration. As result, we present an analytical expression for the basic reproduction number R0. We find that after introducing WNV into Germany, R0 will be above the critical value in many regions of the country. Furthermore, we observe that in the south of Germany, the disease reoccurs in the following season after the introduction. We include a potential distribution map associated with WNV cases in Germany to illustrate our findings in a spatial scale.

Quantum orbital-optimized unitary coupled cluster methods in the strongly correlated regime: Can quantum algorithms outperform their classical equivalents?

The Coupled Cluster (CC) method is used to compute the electronic correlation energy in atoms and molecules and often leads to highly accurate results. However, due to its single-reference nature, standard CC in its projected form fails to describe quantum states characterized by strong electronic correlations and multi-reference projective methods become necessary. On the other hand, quantum algorithms for the solution of many-electron problems have also emerged recently. The quantum unitary variant of CC (UCC) with singles and doubles (q-UCCSD) is a popular wavefunction Ansatz for the variational quantum eigensolver algorithm. The variational nature of this approach can lead to significant advantages compared to its classical equivalent in the projected form, in particular, for the description of strong electronic correlation. However, due to the large number of gate operations required in q-UCCSD, approximations need to be introduced in order to make this approach implementable in a state-of-the-art quantum computer. In this work, we evaluate several variants of the standard q-UCCSD Ansatz in which only a subset of excitations is included. In particular, we investigate the singlet and pair q-UCCD approaches combined with orbital optimization. We show that these approaches can capture the dissociation/distortion profiles of challenging systems, such as H4, H2O, and N2 molecules, as well as the one-dimensional periodic Fermi-Hubbard chain. These results promote the future use of q-UCC methods for the solution of challenging electronic structure problems in quantum chemistry.

Ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and topical applications.

Cellulose acetate (CA), viscose, or artificial silk are biocompatible human-benign derivatives of cellulose, one of the most abundant biopolymers on earth. While various optical materials have been developed from CA, optical CA nanomaterials are nonexistent. Here we report on the assembly of a new family of extremely bright fluorescent CA nanoparticles (CA-dots), which are fully suitable for in vivo imaging / targeting applications. CA-dots can encapsulate a variety of molecular fluorophores. Using various commercially available fluorophores, we demonstrate that the fluorescence of CA-dots can be tuned within the entire UV-VIS-NIR spectrum. We also demonstrate excellent specific targeting of tumors in vivo, when injected in blood in zebrafish (xenograft model of human cervical epithelial cancer), and unusually strong ex-vivo topical labeling of colon cancer in mice utilizing CA folate-functionalized nanoparticles.

Non-monotonous Wetting of Graphene-Mica and MoS2-Mica Interfaces with a Molecular Layer of Water.

Hydration of interfaces with a layer of water is a ubiquitous phenomenon, which has important implications for numerous natural and technologically important processes. Nevertheless, at the nanoscale, the understanding of the wetting process is still limited, since it is experimentally difficult to follow. Here, graphene and monolayers of MoS2 deposited on dry mica are used to investigate wetting of the two-dimensional (2D) material-mica interfaces with a molecularly thin layer of water employing scanning force microscopy in different modes. Wetting occurs non-monotonously in time and space for both types of interfaces. It starts at relative humidities (RH) of 10-17% for graphenes and 8-9% for MoS2 and concludes with a homogeneous layer at 25-30 and 15-20%, respectively. Investigation of the process at the graphene-mica interface indicates that up to about 25% RH, initially a highly compliant and unstable layer of water spreads, which subsequently stabilizes by developing labyrinthine nanostructures. Moreover, these nanostructures exhibit distinct mechanical deformability and dissipation, which is ascribed to different densities of the confined water layer. The laterally structured morphology is explained by the interplay of counteracting long-range dipole-dipole repulsion and short-range line tension, with the latter causing at least in part by the mechanical deformation of the 2D material. The proposed origins of the interactions are common for thin layers of polar molecules at interfaces, implying that the lateral structuring of thin wetting layers at submonolayer concentrations may also be a quite general phenomenon.

Pericellular Brush and Mechanics of Guinea Pig Fibroblast Cells Studied with AFM.

The atomic force microscopy (AFM) indentation method combined with the brush model can be used to separate the mechanical response of the cell body from deformation of the pericellular layer surrounding biological cells. Although self-consistency of the brush model to derive the elastic modulus of the cell body has been demonstrated, the model ability to characterize the pericellular layer has not been explicitly verified. Here we demonstrate it by using enzymatic removal of hyaluronic content of the pericellular brush for guinea pig fibroblast cells. The effect of this removal is clearly seen in the AFM force-separation curves associated with the pericellular brush layer. We further extend the brush model for brushes larger than the height of the AFM probe, which seems to be the case for fibroblast cells. In addition, we demonstrate that an extension of the brush model (i.e., double-brush model) is capable of detecting the hierarchical structure of the pericellular brush, which, for example, may consist of the pericellular coat and the membrane corrugation (microridges and microvilli). It allows us to quantitatively segregate the large soft polysaccharide pericellular coat from a relatively rigid and dense membrane corrugation layer. This was verified by comparison of the parameters of the membrane corrugation layer derived from the force curves collected on untreated cells (when this corrugation membrane part is hidden inside the pericellular brush layer) and on treated cells after the enzymatic removal of the pericellular coat part (when the corrugations are exposed to the AFM probe). We conclude that the brush model is capable of not only measuring the mechanics of the cell body but also the parameters of the pericellular brush layer, including quantitative characterization of the pericellular layer structure.

Load Rate and Temperature Dependent Mechanical Properties of the Cortical Neuron and Its Pericellular Layer Measured by Atomic Force Microscopy.

When studying the mechanical properties of cells by an indentation technique, it is important to take into account the nontrivial pericellular interface (or pericellular "brush") which includes a pericellular coating and corrugation of the pericellular membrane (microvilli and microridges). Here we use atomic force microscopy (AFM) to study the mechanics of cortical neurons taking into account the presence of the above pericellular brush surrounding cell soma. We perform a systematic study of the mechanical properties of both the brush layer and the underlying neuron soma and demonstrate that the brush layer is likely responsible for the low elastic modulus (<1 kPa) typically reported for cortical neurons. When the contribution of the pericellular brush is excluded, the average elastic modulus of the cortical neuron soma is found to be 3-4 times larger than previously reported values measured under similar physiological conditions. We also demonstrate that the underlying soma behaves as a nonviscous elastic material over the indentation rates studied (1-10 µm/s). As a result, it seems that the brush layer is responsible for the previously reported viscoelastic response measured for the neuronal cell body as a whole, within these indentation rates. Due to of the similarities between the macroscopic brain mechanics and the effective modulus of the pericellular brush, we speculate that the pericellular brush layer might play an important role in defining the macroscopic mechanical properties of the brain.

AFM study shows prominent physical changes in elasticity and pericellular layer in human acute leukemic cells due to inadequate cell-cell communication.

Biomechanical properties of single cells in vitro or ex vivo and their pericellular interfaces have recently attracted a lot of attention as a potential biophysical (and possibly prognostic) marker of various diseases and cell abnormalities. At the same time, the influence of the cell environment on the biomechanical properties of cells is not well studied. Here we use atomic force microscopy to demonstrate that cell-cell communication can have a profound effect on both cell elasticity and its pericellular coat. A human pre-B p190BCR/ABL acute lymphoblastic leukemia cell line (ALL3) was used in this study. Assuming that cell-cell communication is inversely proportional to the distance between cells, we study ALL3 cells in vitro growing at different cell densities. ALL3 cells demonstrate a clear density dependent behavior. These cells grow very well if started at a relatively high cell density (HD, >2 × 105 cells ml-1) and are poised to grow at low cell density (LD, <1 × 104 cells ml-1). Here we observe ∼6× increase in the elastic (Young's) modulus of the cell body and ∼3.6× decrease in the pericellular brush length of LD cells compared to HD ALL3 cells. The difference observed in the elastic modulus is much larger than typically reported for pathologically transformed cells. Thus, cell-cell communication must be taken into account when studying biomechanics of cells, in particular, correlating cell phenotype and its biophysical properties.

Biophysical differences between chronic myelogenous leukemic quiescent and proliferating stem/progenitor cells.

The treatment of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder has improved recently, but most patients have not yet been cured. Some patients develop resistance to the available tyrosine kinase treatments. Persistence of residual quiescent CML stem cells (LSCs) that later resume proliferation is another common cause of recurrence or relapse of CML. Eradication of quiescent LSCs is a promising approach to prevent recurrence of CML. Here we report on new biophysical differences between quiescent and proliferating CD34+ LSCs, and speculate how this information could be of use to eradicate quiescent LSCs. Using AFM measurements on cells collected from four untreated CML patients, substantial differences are observed between quiescent and proliferating cells in the elastic modulus, pericellular brush length and its grafting density at the single cell level. The higher pericellular brush densities of quiescent LSCs are common for all samples. The significance of these observations is discussed.

Space-and-time current spectroscopy of a ß-Ga2O3 crystal.

We report the excitation of the non-steady-state photoelectro-motive force in a monoclinic gallium oxide crystal. The crystal grown in an oxygen atmosphere is insulating and highly transparent for a visible light, nevertheless, the formation of dynamic space-charge gratings and observation of the photo-EMF signal is achieved under the laser illumination with wavelength λ = 532 nm. The induced ac current is studied for the cases of zero and non-zero external electric fields, which imply the non-resonant and resonant mechanisms of space-charge recording. The dependencies of the signal amplitude versus the frequency of phase modulation, light intensity, spatial frequency, light polarization and value of the external dc electric field are measured. The material demonstrates the anisotropy along the [100] and [010] directions, namely, there is a weak difference of the transport parameters and a pronounced polarization dependence of the signal. The photoconductivity and diffusion length of electrons are estimated for the chosen light wavelength.

Taming Lévy flights in confined crowded geometries.

We study two-dimensional diffusive motion of a tracer particle in restricted, crowded anisotropic geometries. The underlying medium is formed from a monolayer of elongated molecules [Ciesla J. Chem. Phys. 140, 044706 (2014)] of known concentration. Within this mesh structure, a tracer molecule is allowed to perform a Cauchy random walk with uncorrelated steps. Our analysis shows that the presence of obstacles significantly influences the motion, which in an obstacle-free space would be of a superdiffusive type. At the same time, the selfdiffusive process reveals different anomalous properties, both at the level of a single trajectory realization and after the ensemble averaging. In particular, due to obstacles, the sample mean squared displacement asymptotically grows sublinearly in time, suggesting a non-Markov character of motion. Closer inspection of survival probabilities indicates, however, that the underlying diffusion is memoryless over long time scales despite a strong inhomogeneity of the motion induced by the orientational ordering.