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Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020–2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known:• Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum.• The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New:• Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied.• Routine and semi-professional sports activities seem safe environments to promote during this pandemic.

The COVID-19 pandemic is changing the world in unprecedented and unpredictable ways. Human mobility, being the greatest facilitator for the spread of the virus, is at the epicenter of this change. In order to study mobility under COVID-19, to evaluate the efficiency of mobility restriction policies, and to facilitate a better response to future crisis, we need to understand all possible mobility data sources at our disposal. Our work studies private mobility sources, gathered from mobile-phones and released by large technological companies. These data are of special interest because, unlike most public sources, it is focused on individuals rather than on transportation means. Furthermore, the sample of society they cover is large and representative. On the other hand, these data are not directly accessible for anonymity reasons. Thus, properly interpreting its patterns demands caution. Aware of that, we explore the behavior and inter-relations of private sources of mobility data in the context of Spain. This country represents a good experimental setting due to both its large and fast pandemic peak and its implementation of a sustained, generalized lockdown. Our work illustrates how a direct and naive comparison between sources can be misleading, as certain days (e.g., Sundays) exhibit a directly adverse behavior. After understanding their particularities, we find them to be partially correlated and, what is more important, complementary under a proper interpretation. Finally, we confirm that mobile-data can be used to evaluate the efficiency of implemented policies, detect changes in mobility trends, and provide insights into what new normality means in Spain. Part of this research has received funding from the European Union Horizon 2020 Programme under the SoBigData++ Project, grant agreement num. 871,042. Martí Català received funding from La Caixa Foundation (ID 100010434), under agreement LCF/PR/GN17/50300003; Martí Català received funding from Ministerio de Ciencia, Innovación y Universidades and FEDER, with the project PGC2018-095456-B-I00.E. A-L EAL thanks support from the Spanish Ministry of Science Innovation and Universities, (SAF2017-88019-C3-3R).

Rationale: Ca2+ alternans plays an essential role in cardiac alternans that can lead to ventricular fibrillation, but the mechanism underlying Ca2+ alternans remains undefined. Increasing evidence suggests that Ca2+ alternans results from alternations in the inactivation of cardiac RyR2 (ryanodine receptor 2). However, what inactivates RyR2 and how RyR2 inactivation leads to Ca2+ alternans are unknown. Objective: To determine the role of CaM (calmodulin) on Ca2+ alternans in intact working mouse hearts. Methods and results: We used an in vivo local gene delivery approach to alter CaM function by directly injecting adenoviruses expressing CaM-wild type, a loss-of-function CaM mutation, CaM (1-4), and a gain-of-function mutation, CaM-M37Q, into the anterior wall of the left ventricle of RyR2 wild type or mutant mouse hearts. We monitored Ca2+ transients in ventricular myocytes near the adenovirus-injection sites in Langendorff-perfused intact working hearts using confocal Ca2+ imaging. We found that CaM-wild type and CaM-M37Q promoted Ca2+ alternans and prolonged Ca2+ transient recovery in intact RyR2 wild type and mutant hearts, whereas CaM (1-4) exerted opposite effects. Altered CaM function also affected the recovery from inactivation of the L-type Ca2+ current but had no significant impact on sarcoplasmic reticulum Ca2+ content. Furthermore, we developed a novel numerical myocyte model of Ca2+ alternans that incorporates Ca2+-CaM-dependent regulation of RyR2 and the L-type Ca2+ channel. Remarkably, the new model recapitulates the impact on Ca2+ alternans of altered CaM and RyR2 functions under 9 different experimental conditions. Our simulations reveal that diastolic cytosolic Ca2+ elevation as a result of rapid pacing triggers Ca2+-CaM dependent inactivation of RyR2. The resultant RyR2 inactivation diminishes sarcoplasmic reticulum Ca2+ release, which, in turn, reduces diastolic cytosolic Ca2+, leading to alternations in diastolic cytosolic Ca2+, RyR2 inactivation, and sarcoplasmic reticulum Ca2+ release (ie, Ca2+ alternans). Conclusions: Our results demonstrate that inactivation of RyR2 by Ca2+-CaM is a major determinant of Ca2+ alternans, making Ca2+-CaM dependent regulation of RyR2 an important therapeutic target for cardiac alternans., This work was supported by research grants from the Heart and Stroke Foundation of Canada (G-19-0026444), the Heart and Stroke Foundation Chair in Cardiovascular Research (END611955), the Canadian Institutes of Health Research to S.R.W. Chen (PJT-155940), the Spanish Ministry of Science Innovation and Universities SAF2017-88019-C3-1R, 2R, and 3R (to L. Hove-Madsen, R. Benitez, and B. Echebarria), Marato-TV3 20152030 (to L. Hove-Madsen) and 20151110 (to B. Echebarria), and Generalitat de Catalunya SGR2017-1769 (to L. Hove-Madsen).

CaTo determine the role of CaM (calmodulin) on CaWe used an in vivo local gene delivery approach to alter CaM function by directly injecting adenoviruses expressing CaM-wild type, a loss-of-function CaM mutation, CaM (1-4), and a gain-of-function mutation, CaM-M37Q, into the anterior wall of the left ventricle of RyR2 wild type or mutant mouse hearts. We monitored CaOur results demonstrate that inactivation of RyR2 by Ca

Ventricular contraction is roughly proportional to the amount of calcium released from the Sarcoplasmic Reticulum (SR) during systole. While it is rather straightforward to measure calcium levels and contractibility under different physiological conditions, the complexity of calcium handling during systole and diastole has made the prediction of its release at steady state impossible. Here we approach the problem analyzing the evolution of intracellular and extracellular calcium fluxes during a single beat which is away from homeostatic balance. Using an in-silico subcellular model of rabbit ventricular myocyte, we show that the high dimensional nonlinear problem of finding the steady state can be reduced to a two-variable general equilibrium condition where pre-systolic calcium level in the cytosol and in the SR must fulfill simultaneously two different equalities. This renders calcium homeostasis as a problem that can be studied in terms of its equilibrium structure, leading to precise predictions of steady state from single-beat measurements. We show how changes in ion channels modify the general equilibrium, as shocks would do in general equilibrium macroeconomic models. This allows us to predict when an enhanced entrance of calcium in the cell reduces its contractibility and explain why SERCA gene therapy, a change in calcium handling to treat heart failure, might fail to improve contraction even when it successfully increases SERCA expression., Author summary Cardiomyocytes, upon voltage excitation, release calcium, which leads to cell contraction. However, under some pathological conditions, calcium handling is impaired. Recently, SERCA gene therapy, whose aim is to improve Ca2+ sequestration by the Sarcoplasmic Reticulum (SR), has failed to improve the prognosis of patients with Heart Failure. This, together with recent counterintuitive results in calcium handling, has highlighted the need for a framework to understand calcium homeostasis across species and pathologies. We show here that the proper framework is a general equilibrium approach of two independent variables. The development of this framework allows us to find a possible mechanism for the failure of SERCA gene therapy even when it manages to increase Ca SERCA expression.

Atrial fibrillation (AF), a cardiac arrhythmia characterized by an abnormal heart rythm originated in the atria, is one of the most prevalent cardiac diseases. Although it may have diverse causes, genetic screening has shown that a percentage of pacients suffering of AF present a genetic variant related to disregulation of calcium-activated potassium (SK) channels. In this paper we review the main characteristics of these channels and use several mathematical models of human atrial cardiomyocytes to study their influence in the form of the atrial action potential. We show that an overexpression of SK channels results in decreased action potential duration and, under some circumstances, it may give rise to alternans, suggesting a pro-arrhythmic role of this current. This effect becomes more important at higher pacing rates. Nevertheless, we also find it to protect against spontaneous calcium release induced afterdepolarizations, acting in this case as an antiarrhythmic factor.

Among the different potassium channels present in cardiac myocytes, the small conductance Ca2+ activated potassium channels (SK channels) are particular because they are affected by changes in intracellular calcium. The functional role of these channels in cardiac electrophysiology is still under intense debate. While they do not seem to play an important role in healthy hearts – their associated current, IKCa, is smaller than other potassium currents -, there is increasing evidence that they may become relevant under pathological conditions. In fact, both pro- and anti-arrhythmic effects have been assigned to these channels, depending on the clinical situation. In this work, we have incorporated the current through SK channels, IKCa, into an electrophysiological ionic model of human atria myocyte. This allows us to evaluate changes in the action potential under different parameters affecting the kinetics of these channels. We observe a large dependence of the action potential duration with the conductance and gate dynamics of the channel. The dependence of SK channels with changes in intracellular calcium dynamics helps decreasing the proarrhythmic effect of spontaneous calcium release events

Neuronal networks can spontaneously exhibit periodic bursts of collective activity. High-resolution calcium imaging and computer modelling of in vitro cultures now reveal that this behaviour is a consequence of noise focusing—an implosive concentration of spontaneous activity due to the interplay between network topology and intrinsic neuronal dynamics.

In the heart, rapid pacing rates may induce alternations in the strength of cardiac contraction, termed pulsus alternans. Often, this is due to an instability in the dynamics of the intracellular calcium concentration, whose transients become larger and smaller at consecutive beats. This alternation has been linked experimentally and theoretically to two different mechanisms: an instability due to (1) a strong dependence of calcium release on sarcoplasmic reticulum (SR) load, together with a slow calcium reuptake into the SR or (2) to SR release refractoriness, due to a slow recovery of the ryanodine receptors (RyR2) from inactivation. The relationship between calcium alternans and refractoriness of the RyR2 has been more elusive than the corresponding SR Ca load mechanism. To study the former, we reduce a general calcium model, which mimics the deterministic evolution of a calcium release unit, to its most basic elements. We show that calcium alternans can be understood using a simple nonlinear equation for calcium concentration at the dyadic space, coupled to a relaxation equation for the number of recovered RyR2s. Depending on the number of RyR2s that are recovered at the beginning of a stimulation, the increase in calcium concentration may pass, or not, over an excitability threshold that limits the occurrence of a large calcium transient. When the recovery of the RyR2 is slow, this produces naturally a period doubling bifurcation, resulting in calcium alternans. We then study the effects of inactivation, calcium diffusion, and release conductance for the onset of alternans. We find that the development of alternans requires a well-defined value of diffusion while it is less sensitive to the values of inactivation or release conductance.

In vitro neuronal networks of dissociated hippocampal or cortical tissues are one of the most attractive model systems for the physics and neuroscience communities. Cultured neurons grow and mature, develop axons and dendrites, and quickly connect to their neighbors to establish a spontaneously active network within a week. The resulting neuronal network is characterized by a combination of excitatory and inhibitory neurons coupled through synaptic connections that interact in a highly nonlinear manner. The nonlinear behavior emerges from the dynamics of both the neurons' spiking activity and synaptic transmission, together with biological noise. These ingredients give rise to a rich repertoire of phenomena that are still poorly understood, including the emergence and maintenance of periodic spontaneous activity, avalanches, propagation of fronts and synchronization. In this work we present an overview on the rich activity of cultured neuronal networks, and detail the minimal theoretical considerations needed to describe experimental observations.

Conventional viscous fingering flow in radial Hele-Shaw cells employs a constant injection rate, resulting in the emergence of branched interfacial shapes. The search for mechanisms to prevent the development of these bifurcated morphologies is relevant to a number of areas in science and technology. A challenging problem is how best to choose the pumping rate in order to restrain the growth of interfacial amplitudes. We use an analytical variational scheme to look for the precise functional form of such an optimal flow rate.We find it increases linearly with time in a specific manner so that interface disturbances are minimized. Experiments and nonlinear numerical simulations support the effectiveness of this particularly simple, but nontrivial, pattern controlling process.

We have developed an automatic method for the analysis and identification of dynamical regimes in intracellular calcium patterns from confocal calcium images. The method allows the identification of different dynamical patterns such as spatially concordant and discordant alternans, irregular behavior or phase-locking regimes such as period doubling or halving. The method can be applied to the analysis of different cardiac pathologies related to anomalies at the cellular level such as ventricular reentrant arrhythmias.

We present a model for the actin contractile ring of adherent animal cells. The model suggests that the actin concentration within the ring and consequently the power that the ring exerts both increase during contraction. We demonstrate the crucial role of actin polymerization and depolymerization throughout cytokinesis, and the dominance of viscous dissipation in the dynamics. The physical origin of two phases in cytokinesis dynamics ("biphasic cytokinesis") follows from a limitation on the actin density. The model is consistent with a wide range of measurements of the midzone of dividing animal cells., Comment: PACS numbers: 87.16.Ka, 87.16.Ac http://www.ncbi.nlm.nih.gov/pubmed/16197254 http://www.weizmann.ac.il/complex/tlusty/papers/PhysRevLett2005.pdf

We study the evolution of a family of dumbbell-shaped liquid patches surrounded by air inside a rotating Hele-Shaw cell with lubrication methods and numerical simulations. Depending on initial conditions, the dumbbell either stretches to infinity, pinches off at the neck to form a droplet, or collects into a circular drop at the center of rotation. Whether or not pinch-off occurs results from a subtle interplay between centrifugal and capillary forces. In particular, rotation may delay or even prevent pinch-off from occurring owing to stretching and smoothing of the fluid neck. However, frequently rotation may have the opposite effect leading to pinch-off where the relaxation toward a circular drop would be observed in an ordinary Hele-Shaw cell.

Viscous fingering dynamics driven by centrifugal forcing is studied for arbitrary viscosity contrast. Theoretical methods, including exact solutions, and numerics based on a phase-field approach are used. Both confirm that pinch-off singularities in patterns originated from the centrifugally driven instability may occur spontaneously and be inherent to the two-dimensional Hele-Shaw dynamics. They are systematically more frequent for lower viscosity contrasts consistently with experimental evidence. The analytical insights provide an interpretation of this fact in terms of the asymptotic matching of the different regions of the fingering patterns. The phase-field numerical scheme is shown to be particularly adequate to elucidate the existence of finite-time singularities through the dependence of the singularity time on the interface thickness, in particular for varying viscosity contrast.

Cardiac mechanoelectric feedback can play an important role in different heart pathologies. In this paper, we show that mechanoelectric models which describe both the electric propagation and the mechanic contraction of cardiac tissue naturally lead to close systems of equations with global coupling among the variables. This point is exemplified using the Nash-Panfilov model, which reduces to a FitzHugh-Nagumo-type equation with global coupling in the linear elastic regime. We explain the appearance of self-oscillatory regimes in terms of the system nullclines and describe the different dynamical attractors. Finally, we study their basin of attraction in terms of the system size and the strength of the stretch-induced currents.

We develop a method to quantify the changes in heart rate dynamics during local myocardial ischemia induced by a percutaneous transluminal coronary angioplasty procedure (PTCA). The method introduces an index measuring the nonlinear content of the beat-to-beat (RR) time series by using nonlinear time series techniques such as surrogate data analysis and average mutual information. The index is applied to RR data from 67 subjects obtained before, during, and after the ischemic period and shows an increase in the nonlinearity of the cardiac control dynamics during ischemic and reperfusion stages. The nonlinear index is also used to characterize the effects of performing the coronary occlusion at different arteries and distances. We observe that the effect of ischemia becomes larger as the occlusion distance is reduced, and that most of the changes in the nonlinear content of the dynamics occur at long time scales typically related to sympathetic modulation of the cardiac rhythm (6-25 s).

The goal of this paper is to describe the effects of simple electro-mechanical coupling in isotropic two-dimensional (2D) cardiac tissue. To this aim, we show that the Nash-Panfilov two variable model [PRL 95, 258104 (2005)] for electrical activation, which couples active stress directly to transmembrane potential, can be reduced in the linearly elastic regime to an excitatory system with global coupling. In the linear limit, numerical simulations of both models give the same dynamic evolution, including the appearance of an ectopic focus with origin at the center. Indeed, after an initial excitation, mechano-electrical coupling can generate sustained oscillations in the form of successive waves originated at the center. These oscillations have a large basin of attraction for different sample lengths and values of the stretching current, specially when the recovery time of the excitatory cells is short. We finally present and discuss the appearance of oscillatory waves whose origin is not the center of the 2D sample but a ring of tissue around it. These waves appear spontaneously under some conditions even when the first excitation is generated at the center.

The development of immiscible viscous fingering patterns in a rotating Hele-Shaw cell is investigated. We focus on understanding how the time evolution and the resulting morphologies are affected by the action of the Coriolis force. The problem is approached analytically and numerically by employing a vortex sheet formalism. The vortex sheet strength and a linear dispersion relation are derived analytically, revealing that the most relevant Coriolis force contribution comes from the normal component of the averaged interfacial velocity. It is shown that this normal velocity, uniquely due to the presence of the Coriolis force, is responsible for the complex-valued nature of the linear dispersion relation making the linear phases vary with time. Fully nonlinear stages are studied through intensive numerical simulations. A suggestive interplay between inertial and viscous effects is found, which modifies the dynamics, leading to different pattern-forming structures. The inertial Coriolis contribution plays a characteristic role: it generates a phase drift by deviating the fingers in the sense opposite to the actual rotation of the cell. However, the direction and intensity of finger bending is predominantly determined by viscous effects, being sensitive to changes in the magnitude and sign of the viscosity contrast. The finger competition behavior at advanced time stages is also discussed. © 2008 The American Physical Society.

Thoughts and ideas are multidimensional and often concurrent, yet they can be expressed surprisingly well sequentially by the translation into language. This reduction of dimensions occurs naturally but requires memory and necessitates the existence of correlations, e.g., in written text. However, correlations in word appearance decay quickly, while previous observations of long-range correlations using random walk approaches yield little insight on memory or on semantic context. Instead, we study combinations of words that a reader is exposed to within a “window of attention,” spanning about 100 words. We define a vector space of such word combinations by looking at words that co-occur within the window of attention, and analyze its structure. Singular value decomposition of the co-occurrence matrix identifies a basis whose vectors correspond to specific topics, or “concepts” that are relevant to the text. As the reader follows a text, the “vector of attention” traces out a trajectory of directions in this “concept space.” We find that memory of the direction is retained over long times, forming power-law correlations. The appearance of power laws hints at the existence of an underlying hierarchical network. Indeed, imposing a hierarchy similar to that defined by volumes, chapters, paragraphs, etc. succeeds in creating correlations in a surrogate random text that are identical to those of the original text. We conclude that hierarchical structures in text serve to create long-range correlations, and use the reader’s memory in reenacting some of the multidimensionality of the thoughts being expressed.

The different finger morphologies that arise at the interface separating two immiscible fluids in a rotating Hele-Shaw cell are studied numerically. The whole range of viscosity contrast is analyzed and a variety of fingering patterns systematically introduced, including the case in which the inner fluid is less viscous than the outer one. Our numerical results demonstrate that both the magnitude and the sign of the viscosity contrast strongly affect the shape of the emerging fingers, and also their length distribution. We have also found that the occurrence and location of pinch-off singularities are remarkably modified when the inner fluid is less viscous: instead of generating an isolated detaching drop, a full finger is disconnected from the interface. Finally, we have verified that the finger competition phenomena revealed by our simulations are correctly predicted by a weakly nonlinear analysis of the pattern development, showing that such important finger competition dynamics is already set at relatively early stages of interfacial evolution.

We study the fingering instability of a circular interface between two immiscible liquids in a radial Hele-Shaw cell. The cell rotates around its vertical symmetry axis, and the instability is driven by the density difference between the two fluids. This kind of driving allows studying the interfacial dynamics in the particularly interesting case of an interface separating two liquids of comparable viscosity. An accurate experimental study of the number of fingers emerging from the instability reveals a slight but systematic dependence of the linear dispersion relation on the gap spacing. We show that this result is related to a modification of the interface boundary condition which incorporates stresses originated from normal velocity gradients. The early nonlinear regime shows nearly no competition between the outgrowing fingers, characteristic of low viscosity contrast flows. We perform experiments in a wide range of experimental parameters, under conditions of mass conservation (no injection), and characterize the resulting patterns by data collapses of two characteristic lengths: the radius of gyration of the pattern and the interface stretching. Deep in the nonlinear regime, the fingers which grow radially outwards stretch and become gradually thinner, to a point that the fingers pinch and emit drops. We show that the amount of liquid emitted in the first generation of drops is a constant independent of the experimental parameters. Further on there is a sharp reduction of the amount of liquid centrifugated, punctuated by periods of no observable centrifugation.

We show, both theoretically and experimentally, that the interface between two viscous fluids in a Hele-Shaw cell can be nonlinearly unstable before the Saffman-Taylor linear instability point is reached. We identify the family of exact elastica solutions [Nye et al., Eur. J. Phys. 5, 73 (1984)]] as the unstable branch of the corresponding subcritical bifurcation which ends up at a topological singularity defined by interface pinchoff. We devise an experimental procedure to prepare arbitrary initial conditions in a Hele-Shaw cell. This is used to test the proposed bifurcation scenario and quantitatively asses its practical relevance.

We present a weakly nonlinear analysis of the interface dynamics in a radial Hele-Shaw cell driven by both injection and rotation. We extend the systematic expansion introduced in [E. Alvarez-Lacalle et al., Phys. Rev. E 64, 016302 (2001)] to the radial geometry, and compute explicitly the first nonlinear contributions. We also find the necessary and sufficient condition for the uniform convergence of the nonlinear expansion. Within this region of convergence, the analytical predictions at low orders are compared satisfactorily to exact solutions and numerical integration of the problem. This is particularly remarkable in configurations (with no counterpart in the channel geometry) for which the interplay between injection and rotation allows that condition to be satisfied at all times. In the case of the purely centrifugal forcing we demonstrate that nonlinear couplings make the interface more unstable for lower viscosity contrast between the fluids.

Calcium alternans is a pro-arrhytmic cardiac dysfunction related to beat-to-beat changes in the amplitude of intracellular calcium transient, that typically occurs at rapid pacing rates. Although oscillations in sarcoplasmic reticulum (SR) content have been related with calcium alternans, the experimental appearance of alternans without these oscillations suggests that another mechanism related with refractoriness of SR calcium release might be key, at least, under certain conditions. We investigate how RyR2 refractoriness modulates calcium handling on a beat-to-beat basis using a numerical rabbit cardiomyocyte model. We find that a slow recovery from inactivation of the RyR2 might be crucial. On one hand, a steep relation between sarcoplasmic reticulum (SR) load and calcium release makes regular calcium cycling unstable at high SR calcium load and/or fast pacing rates, in agreement with previous explanation when RyR2 inactivation is not important. On the other hand, we show that calcium release can also depend strongly on the number of RyR2 ready to open if an important number of RyR2s inactivate after the release. This gives rise to a steep nonlinear relation between the calcium release and the level of recovered RyR2, so that a small change in the later produces big changes in calcium release. A conclusion of this result is that RyR2 refractoriness can be the main nonlinearity behind alternans even when alternation in SR-Ca load is present.

In this paper we use a simplified model of cardiac excitation-contraction coupling to study the effect of tissue deformation on the dynamics of alternans, i.e., alternations in the duration of the cardiac action potential, that occur at fast pacing rates and are known to be proarrhythmic. We show that small stretch-activated currents can produce large effects and cause a transition from in-phase to off-phase alternations (i.e., from concordant to discordant alternans) and to conduction blocks. We demonstrate numerically and analytically that this effect is the result of a generic change in the slope of the conduction velocity restitution curve due to electromechanical coupling. Thus, excitation-contraction coupling can potentially play a relevant role in the transition to reentry and fibrillation.

We demonstrate that wetting effects at moving contact lines have a strong impact in viscous fingering patterns. Experiments in a rotating Hele-Shaw (HS) cell, dry or prewetted, show consistent morphological differences. When the wetting fluid invades a dry region, contact angle dynamics yield a kinetic contribution to the interface pressure drop that scales with capillary number as ${\mathrm{Ca}}^{2∕3}$ but is significantly larger than the Park-Homsy kinetic correction. Numerical results are in very good agreement with experiments and show that standard HS equations work best for prewetted cells.

Electromechanical alternans is a beat-to-beat alterna- tion in the strength of contraction of a cardiac cell which appears often due to an instability of calcium cycling. The global calcium signal in cardiomyocytes is the result of the combined effect of several thousand micron scale domains called Calcium Release Units (CaRU), coupled through diffusion, where the flow of calcium among different cell compartments is regulated by stochastic signaling involv- ing the ryanodine receptor (RyR). Recently, numerical sim- ulations have suggested that the transition from regular Ca cycling to alternans is an order-disorder phase transition consistent with the Ising universality class. Inside the cell, groups of CaRU form transient areas within the cell where alternans appear. However, global alternans appears only as a result of the synchronization of the oscillation phase among different subunits. We show here that this transi- tion is indeed robust and universal upon changes in the behavior of the RyR. Using three different set of parame- ters for the transition rates among open, closed and inacti- vated states in the RyR, we show that different RyR behav- ior leads to the same type of order-disorder transition.

We develop a systematic method to derive all orders of mode couplings in a weakly nonlinear approach to the dynamics of the interface between two immiscible viscous fluids in a Hele-Shaw cell. The method is completely general. It includes both the channel geometry driven by gravity and pressure, and the radial geometry with arbitrary injection and centrifugal driving. We find the finite radius of convergence of the mode-coupling expansion. In the channel geometry we carry out the calculation up to third-order couplings, which is necessary to account for the time-dependent Saffman-Taylor finger solution and the case of zero viscosity contrast. Both in the channel and the radial geometries, the explicit results provide relevant analytical information about the role that the viscosity contrast and the surface tension play in the dynamics. We finally check the quantitative validity of different orders of approximation against a physically relevant, exact time-dependent solution. The agreement between the low order approximations and the exact solution is excellent within the radius of convergence, and reasonably good even beyond that., 17 pages, 9 figures

Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switch-like properties which are critical to their biological function. In this study, we investigate how the properties of these signaling systems depend on the network architecture. Our main result is that these nonlinear networks exhibit bistability where the network activity can switch between states that correspond to a low and high activity level. We show that this bistable regime emerges at a critical coupling strength that is determined by the spectral structure of the network. In particular, the set of nodes that correspond to large components of the leading eigenvector of the adjacency matrix determines the onset of bistability. Above this transition, the eigenvectors of the adjacency matrix determine a hierarchy of clusters, defined by its spectral properties, which are activated sequentially with increasing network activity. We argue further that the onset of bistability occurs either continuously or discontinuously depending upon whether the leading eigenvector is localized or delocalized. Finally, we show that at low network coupling stochastic transitions to the active branch are also driven by the set of nodes that contribute more strongly to the leading eigenvector., 30 pages, 12 figures