Vorticity-Strain Rate Dynamics and the Smallest Scales of Turbulence.

Building upon the intrinsic properties of Navier-Stokes dynamics, namely the prevalence of intense vortical structures and the interrelationship between vorticity and strain rate, we propose a simple framework to quantify the extreme events and the smallest scales of turbulence. We demonstrate that our approach is in excellent agreement with the best available data from direct numerical simulations of isotropic turbulence, with Taylor-scale Reynolds numbers up to 1300. We additionally highlight a shortcoming of prevailing intermittency models due to their disconnection from the observed correlation between vorticity and strain. Our work accentuates the importance of this correlation as a crucial step in developing an accurate understanding of intermittency in turbulence.

Bio-hybrid micro-swimmers propelled by flagella isolated from C. reinhardtii.

Bio-hybrid micro-swimmers, composed of biological entities integrated with synthetic constructs, actively transport cargo by converting chemical energy into mechanical work. Here, using isolated and demembranated flagella from green algae Chlamydomonas reinhardtii (C. reinhardtii), we build efficient axonemally-driven micro-swimmers that consume ATP to propel micron-sized beads. Depending on the calcium concentration, we observed two main classes of motion: whereas beads move along curved trajectories at calcium concentrations below 0.03 mM, they are propelled along straight paths when the calcium concentration increases. In this regime, they reached velocities of approximately 20 µm s-1, comparable to human sperm velocity in vivo. We relate this transition to the properties of beating axonemes, in particular the reduced static curvature with increasing calcium concentration. Our designed system has potential applications in the fabrication of synthetic micro-swimmers, and in particular, bio-actuated medical micro-robots for targeted drug delivery.

Generation of intense dissipation in high Reynolds number turbulence.

Intense fluctuations of energy dissipation rate in turbulent flows result from the self-amplification of strain rate via a quadratic nonlinearity, with contributions from vorticity (via the vortex stretching mechanism) and pressure-Hessian-which are analysed here using direct numerical simulations of isotropic turbulence on up to [Formula: see text] grid points, and Taylor-scale Reynolds numbers in the range 140-1300. We extract the statistics involved in amplification of strain and condition them on the magnitude of strain. We find that strain is self-amplified by the quadratic nonlinearity, and depleted via vortex stretching, whereas pressure-Hessian acts to redistribute strain fluctuations towards the mean-field and hence depletes intense strain. Analysing the intense fluctuations of strain in terms of its eigenvalues reveals that the net amplification is solely produced by the third eigenvalue, resulting in strong compressive action. By contrast, the self-amplification acts to deplete the other two eigenvalues, whereas vortex stretching acts to amplify them, with both effects cancelling each other almost perfectly. The effect of the pressure-Hessian for each eigenvalue is qualitatively similar to that of vortex stretching, but significantly weaker in magnitude. Our results conform with the familiar notion that intense strain is organized in sheet-like structures, which are in the vicinity of, but never overlap with tube-like regions of intense vorticity due to fundamental differences in their amplifying mechanisms. This article is part of the theme issue 'Scaling the turbulence edifice (part 1)'.

Strain- or Stress-Sensing in Mechanochemical Patterning by the Phytohormone Auxin.

Both chemical and mechanical fields are known to play a major role in morphogenesis. In plants, the phytohormone auxin and its directional transport are essential for the formation of robust patterns of organs, such as flowers or leaves, known as phyllotactic patterns. The transport of auxin was recently shown to be affected by mechanical signals, and conversely, auxin accumulation in incipient organs affects the mechanical properties of the cells. The precise interaction between mechanical fields and auxin transport, however, is poorly understood. In particular, it is unknown whether transport is sensitive to the strain or to the stress exerted on a given cell. Here, we investigate the nature of this coupling with the help of theoretical models. Namely, we introduce the effects of either mechanical stress or mechanical strain in a model of auxin transport and compare the patterns predicted with available experimental results, in which the tissue is perturbed by ablations, chemical treatments, or genetic manipulations. We also study the robustness of the patterning mechanism to noise and investigate the effect of a shock that changes abruptly its parameters. Although the model predictions with the two different feedbacks are often indistinguishable, the strain feedback seems to better agree with some of the experiments. The computational modeling approach used here, which enables us to distinguish between several possible mechanical feedbacks, offers promising perspectives to elucidate the role of mechanics in tissue development, and may help providing insight into the underlying molecular mechanisms.

Can Hail and Rain Nucleate Cloud Droplets?

We present results from moist convection in a mixture of pressurized sulfur hexafluoride (liquid and vapor), and helium (gas) to model the wet and dry components of the Earth's atmosphere. To allow for homogeneous nucleation, we operate the experiment close to critical conditions. We report on the nucleation of microdroplets in the wake of large cold liquid drops falling through the supersaturated atmosphere and show that the homogeneous nucleation is caused by isobaric cooling of the saturated sulfur hexafluoride vapor. Our results carry over to atmospheric clouds: falling hail and cold rain drops may enhance the heterogeneous nucleation of microdroplets in their wake under supersaturated atmospheric conditions. We also observed that under appropriate circumstances settling microdroplets form a rather stable horizontal cloud layer, which separates regions of super- and subcritical saturation.

Variability and Order in Cytoskeletal Dynamics of Motile Amoeboid Cells.

The chemotactic motion of eukaryotic cells such as leukocytes or metastatic cancer cells relies on membrane protrusions driven by the polymerization and depolymerization of actin. Here we show that the response of the actin system to a receptor stimulus is subject to a threshold value that varies strongly from cell to cell. Above the threshold, we observe pronounced cell-to-cell variability in the response amplitude. The polymerization time, however, is almost constant over the entire range of response amplitudes, while the depolymerization time increases with increasing amplitude. We show that cell-to-cell variability in the response amplitude correlates with the amount of Arp2/3, a protein that enhances actin polymerization. A time-delayed feedback model for the cortical actin concentration is consistent with all our observations and confirms the role of Arp2/3 in the observed cell-to-cell variability. Taken together, our observations highlight robust regulation of the actin response that enables a reliable timing of cell movement.

Low-energy control of electrical turbulence in the heart.

Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult, because of the nonlinear interaction of excitation waves in a heterogeneous anatomical substrate. In the absence of a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation. Here we establish the relationship between the response of the tissue to an electric field and the spatial distribution of heterogeneities in the scale-free coronary vascular structure. We show that in response to a pulsed electric field, E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density ρ(E) and a characteristic time, τ, for tissue depolarization that obeys the power law τ ∝ E(α). These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. We show in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore, efficient termination of fibrillation. Using this control strategy, we demonstrate low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques.

Flight-crash events in turbulence.

The statistical properties of turbulence differ in an essential way from those of systems in or near thermal equilibrium because of the flux of energy between vastly different scales at which energy is supplied and at which it is dissipated. We elucidate this difference by studying experimentally and numerically the fluctuations of the energy of a small fluid particle moving in a turbulent fluid. We demonstrate how the fundamental property of detailed balance is broken, so that the probabilities of forward and backward transitions are not equal for turbulence. In physical terms, we found that in a large set of flow configurations, fluid elements decelerate faster than accelerate, a feature known all too well from driving in dense traffic. The statistical signature of rare "flight-crash" events, associated with fast particle deceleration, provides a way to quantify irreversibility in a turbulent flow. Namely, we find that the third moment of the power fluctuations along a trajectory, nondimensionalized by the energy flux, displays a remarkable power law as a function of the Reynolds number, both in two and in three spatial dimensions. This establishes a relation between the irreversibility of the system and the range of active scales. We speculate that the breakdown of the detailed balance characterized here is a general feature of other systems very far from equilibrium, displaying a wide range of spatial scales.

Single-Particle Motion and Vortex Stretching in Three-Dimensional Turbulent Flows.

Three-dimensional turbulent flows are characterized by a flux of energy from large to small scales, which breaks the time reversal symmetry. The motion of tracer particles, which tend to lose energy faster than they gain it, is also irreversible. Here, we connect the time irreversibility in the motion of single tracers with vortex stretching and thus with the generation of the smallest scales.

Noisy Oscillations in the Actin Cytoskeleton of Chemotactic Amoeba.

Biological systems with their complex biochemical networks are known to be intrinsically noisy. Here we investigate the dynamics of actin polymerization of amoeboid cells, which are close to the onset of oscillations. We show that the large phenotypic variability in the polymerization dynamics can be accurately captured by a generic nonlinear oscillator model in the presence of noise. We determine the relative role of the noise with a single dimensionless, experimentally accessible parameter, thus providing a quantitative description of the variability in a population of cells. Our approach, which rests on a generic description of a system close to a Hopf bifurcation and includes the effect of noise, can characterize the dynamics of a large class of noisy systems close to an oscillatory instability.

Time-reversal-symmetry breaking in turbulence.

In three-dimensional turbulent flows, the flux of energy from large to small scales breaks time symmetry. We show here that this irreversibility can be quantified by following the relative motion of several Lagrangian tracers. We find by analytical calculation, numerical analysis, and experimental observation that the existence of the energy flux implies that, at short times, two particles separate temporally slower forwards than backwards, and the difference between forward and backward dispersion grows as t^{3}. We also find the geometric deformation of material volumes, defined by four points spanning an initially regular tetrahedron, to show sensitivity to the time reversal with an effect growing linearly in t. We associate this with the structure of the strain rate in the flow.

Flagellum-driven cargoes: Influence of cargo size and the flagellum-cargo attachment geometry.

The beating of cilia and flagella, which relies on an efficient conversion of energy from ATP-hydrolysis into mechanical work, offers a promising way to propel synthetic cargoes. Recent experimental realizations of such micro-swimmers, in which micron-sized beads are propelled by isolated and demembranated flagella from the green algae Chlamydomonas reinhardtii (C. reinhardtii), revealed a variety of propulsion modes, depending in particular on the calcium concentration. Here, we investigate theoretically and numerically the propulsion of a bead as a function of the flagellar waveform and the attachment geometries between the bead and the flagellum. To this end, we take advantage of the low Reynolds number of the fluid flows generated by the micro-swimmer, which allows us to neglect fluid inertia. By describing the flagellar waveform as a superposition of a static component and a propagating wave, and using resistive-force theory, we show that the asymmetric sideways attachment of the flagellum to the bead makes a contribution to the rotational velocity of the micro-swimmer that is comparable to the contribution caused by the static component of the flagellar waveform. Remarkably, our analysis reveals the existence of a counter-intuitive propulsion regime in which an increase in the size of the cargo, and hence its drag, leads to an increase in some components of the velocity of the bead. Finally, we discuss the relevance of the uncovered mechanisms for the fabrication of synthetic, bio-actuated medical micro-robots for targeted drug delivery.

Multi-channel electrohysterography enabled uterine contraction characterization and its effect in delivery assessment.

Uterine contractions are routinely monitored by tocodynamometer (TOCO) at late stage of pregnancy to predict the onset of labor. However, TOCO reveals no information on the synchrony and coherence of contractions, which are important contributors to a successful delivery. The electrohysterography (EHG) is a recording of the electrical activities that trigger the local muscles to contract. The spatial-temporal information embedded in multiple channel EHG signals make them ideal for characterizing the synchrony and coherence of uterine contraction. To proceed, contractile time-windows are identified from TOCO signals and are then used to segment out the simultaneously recorded EHG signals of different channels. We construct sample entropy SamEn and Concordance Correlation based feature ψ from these EHG segments to quantify the synchrony and coherence of contraction. To test the effectiveness of the proposed method, 122 EHG recordings in the Icelandic EHG database were divided into two groups according to the time difference between the gestational ages at recording and at delivery (TTD). Both SamEn and ψ show clear difference in the two groups (p<10-5) even when measurements were made 120 h before delivery. Receiver operating characteristic curve analysis of these two features gave AUC values of 0.834 and 0.726 for discriminating imminent labor defined with TTD ≤ 24 h. The SamEn was significantly smaller in women (0.1433) of imminent labor group than in women (0.3774) of the pregnancy group. Using an optimal cutoff value of SamEn to identify imminent labor gives sensitivity, specificity, and accuracy as high as 0.909, 0.712 and 0.743, respectively. These results demonstrate superiority in comparing to the existing SOTA methods. This study is the first research work focusing on characterizing the synchrony property of contractions from the electrohysterography signals. Despite the very limited dataset used in the validation process, the promising results open a new direction to the use of electrohysterography in obstetrics.

Self-organized transition to coherent activity in disordered media.

Synchronized oscillations are of critical functional importance in many biological systems. We show that such oscillations can arise without centralized coordination in a disordered system of electrically coupled excitable and passive cells. Increasing the coupling strength results in waves that lead to coherent periodic activity, exhibiting cluster, local and global synchronization under different conditions. Our results may explain the self-organized transition in a pregnant uterus from transient, localized activity initially to system-wide coherent excitations just before delivery.

Epistasis in a model of molecular signal transduction.

Biological functions typically involve complex interacting molecular networks, with numerous feedback and regulation loops. How the properties of the system are affected when one, or several of its parts are modified is a question of fundamental interest, with numerous implications for the way we study and understand biological processes and treat diseases. This question can be rephrased in terms of relating genotypes to phenotypes: to what extent does the effect of a genetic variation at one locus depend on genetic variation at all other loci? Systematic quantitative measurements of epistasis--the deviation from additivity in the effect of alleles at different loci--on a given quantitative trait remain a major challenge. Here, we take a complementary approach of studying theoretically the effect of varying multiple parameters in a validated model of molecular signal transduction. To connect with the genotype/phenotype mapping we interpret parameters of the model as different loci with discrete choices of these parameters as alleles, which allows us to systematically examine the dependence of the signaling output--a quantitative trait--on the set of possible allelic combinations. We show quite generally that quantitative traits behave approximately additively (weak epistasis) when alleles correspond to small changes of parameters; epistasis appears as a result of large differences between alleles. When epistasis is relatively strong, it is concentrated in a sparse subset of loci and in low order (e.g. pair-wise) interactions. We find that focusing on interaction between loci that exhibit strong additive effects is an efficient way of identifying most of the epistasis. Our model study defines a theoretical framework for interpretation of experimental data and provides statistical predictions for the structure of genetic interaction expected for moderately complex biological circuits.

Rotational intermittency and turbulence induced lift experienced by large particles in a turbulent flow.

The motion of a large, neutrally buoyant, particle freely advected by a turbulent flow is determined experimentally. We demonstrate that both the translational and angular accelerations exhibit very wide probability distributions, a manifestation of intermittency. The orientation of the angular velocity with respect to the trajectory, as well as the translational acceleration conditioned on the spinning velocity, provides evidence of a lift force acting on the particle.

Systems analysis of the single photon response in invertebrate photoreceptors.

Photoreceptors of Drosophila compound eye employ a G protein-mediated signaling pathway that transduces single photons into transient electrical responses called "quantum bumps" (QB). Although most of the molecular components of this pathway are already known, the system-level understanding of the mechanism of QB generation has remained elusive. Here, we present a quantitative model explaining how QBs emerge from stochastic nonlinear dynamics of the signaling cascade. The model shows that the cascade acts as an "integrate and fire" device and explains how photoreceptors achieve reliable responses to light although keeping low background in the dark. The model predicts the nontrivial behavior of mutants that enhance or suppress signaling and explains the dependence on external calcium, which controls feedback regulation. The results provide insight into physiological questions such as single-photon response efficiency and the adaptation of response to high incident-light level. The system-level analysis enabled by modeling phototransduction provides a foundation for understanding G protein signaling pathways less amenable to quantitative approaches.

Realistic preterm prediction based on optimized synthetic sampling of EHG signal.

Preterm labor is the leading cause of neonatal morbidity and mortality in newborns and has attracted significant research attention from many scientific areas. The relationship between uterine contraction and the underlying electrical activities makes uterine electrohysterogram (EHG) a promising direction for detecting and predicting preterm births. However, due to the scarcity of EHG signals, especially those leading to preterm births, synthetic algorithms have been used to generate artificial samples of preterm birth type in order to eliminate bias in the prediction towards normal delivery, at the expense of reducing the feature effectiveness in automatic preterm detection based on machine learning. To address this problem, we quantify the effect of synthetic samples (balance coefficient) on the effectiveness of features and form a general performance metric by using several feature scores with relevant weights that describe their contributions to class segregation. In combination with the activation/inactivation functions that characterize the effect of the abundance of training samples on the accuracy of the prediction of preterm and normal birth delivery, we obtained an optimal sample balance coefficient that compromises the effect of synthetic samples in removing bias toward the majority group (i.e., normal delivery and the side effect of reducing the importance of features). A more realistic predictive accuracy was achieved through a series of numerical tests on the publicly available TPEHG database, therefore demonstrating the effectiveness of the proposed method.

Termination of atrial fibrillation using pulsed low-energy far-field stimulation.

BACKGROUND: Electrically based therapies for terminating atrial fibrillation (AF) currently fall into 2 categories: antitachycardia pacing and cardioversion. Antitachycardia pacing uses low-intensity pacing stimuli delivered via a single electrode and is effective for terminating slower tachycardias but is less effective for treating AF. In contrast, cardioversion uses a single high-voltage shock to terminate AF reliably, but the voltages required produce undesirable side effects, including tissue damage and pain. We propose a new method to terminate AF called far-field antifibrillation pacing, which delivers a short train of low-intensity electric pulses at the frequency of antitachycardia pacing but from field electrodes. Prior theoretical work has suggested that this approach can create a large number of activation sites ("virtual" electrodes) that emit propagating waves within the tissue without implanting physical electrodes and thereby may be more effective than point-source stimulation. METHODS AND RESULTS: Using optical mapping in isolated perfused canine atrial preparations, we show that a series of pulses at low field strength (0.9 to 1.4 V/cm) is sufficient to entrain and subsequently extinguish AF with a success rate of 93% (69 of 74 trials in 8 preparations). We further demonstrate that the mechanism behind far-field antifibrillation pacing success is the generation of wave emission sites within the tissue by the applied electric field, which entrains the tissue as the field is pulsed. CONCLUSIONS: AF in our model can be terminated by far-field antifibrillation pacing with only 13% of the energy required for cardioversion. Further studies are needed to determine whether this marked reduction in energy can increase the effectiveness and safety of terminating atrial tachyarrhythmias clinically.

Self-attenuation of extreme events in Navier-Stokes turbulence.

Turbulent fluid flows are ubiquitous in nature and technology, and are mathematically described by the incompressible Navier-Stokes equations. A hallmark of turbulence is spontaneous generation of intense whirls, resulting from amplification of the fluid rotation-rate (vorticity) by its deformation-rate (strain). This interaction, encoded in the non-linearity of Navier-Stokes equations, is non-local, i.e., depends on the entire state of the flow, constituting a serious hindrance in turbulence theory and even establishing regularity of the equations. Here, we unveil a novel aspect of this interaction, by separating strain into local and non-local contributions utilizing the Biot-Savart integral of vorticity in a sphere of radius R. Analyzing highly-resolved numerical turbulent solutions to Navier-Stokes equations, we find that when vorticity becomes very large, the local strain over small R surprisingly counteracts further amplification. This uncovered self-attenuation mechanism is further shown to be connected to local Beltramization of the flow, and could provide a direction in establishing the regularity of Navier-Stokes equations.