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Cancer is a complex disease and thus is complicated to model. However, simple models that describe the main processes involved in tumoral dynamics, e.g., competition and mutation, can give us clues about cancer behaviour, at least qualitatively, also allowing us to make predictions. Here we analyze a simplified quasispecies mathematical model given by differential equations describing the time behaviour of tumor cells populations with different levels of genomic instability. We find the equilibrium points, also characterizing their stability and bifurcations focusing on replication and mutation rates. We identify a transcritical bifurcation at increasing mutation rates of the tumor cells population. Such a bifurcation involves an scenario with dominance of healthy cells and impairment of tumor populations. Finally, we characterize the transient times for this scenario, showing that a slight increase beyond the critical mutation rate may be enough to have a fast response towards the desired state (i.e., low tumor populations) during directed mutagenic therapies.

Part I of this paper, namely Sreenath, Oh, Krishnaprasad, and Marsden [1987], hereafter denoted [I] studied the Hamiltonian structure and equilibria for interconnected planar rigid bodies, with the primary focus being on the case of three bodies coupled with hinge joints. The Hamiltonian structure was obtained by the reduction technique, starting with the canonical Hamiltonian structure in material representation and then quotienting by the group of Euclidean motions.

In this paper we study the breakdown of normal hyperbolicity and its consequences for reaction dynamics; in particular, the dividing surface, the flux through the dividing surface (DS), and the gap time distribution. Our approach is to study these questions using simple, two degree-of-freedom Hamiltonian models where calculations for the different geometrical and dynamical quantities can be carried out exactly. For our examples, we show that resonances within the normally hyperbolic invariant manifold may, or may not, lead to a `loss of normal hyperbolicity'. Moreover, we show that the onset of such resonances results in a change in topology of the dividing surface, but does not affect our ability to define a DS. The flux through the DS varies continuously with energy, even as the energy is varied in such a way that normal hyperbolicity is lost. For our examples the gap time distributions exhibit singularities at energies corresponding to the existence of homoclinic orbits in the DS, but these singularities are not associated with loss of normal hyperbolicity.

Search for possible relationships between phylogeny and ontogeny is one of the most important issues in the field of evolutionary developmental biology. By representing developmental dynamics of spatially located cells with gene expression dynamics with cell-to-cell interaction under external morphogen gradient, evolved are gene regulation networks under mutation and selection with the fitness to approach a prescribed spatial pattern of expressed genes. For most of thousands of numerical evolution experiments, evolution of pattern over generations and development of pattern by an evolved network exhibit remarkable congruence. Here, both the pattern dynamics consist of several epochs to form successive stripe formations between quasi-stationary regimes. In evolution, the regimes are generations needed to hit relevant mutations, while in development, they are due to the emergence of slowly varying expression that controls the pattern change. Successive pattern changes are thus generated, which are regulated by successive combinations of feedback or feedforward regulations under the upstream feedforward network that reads the morphogen gradient. By using a pattern generated by the upstream feedforward network as a boundary condition, downstream networks form later stripe patterns. These epochal changes in development and evolution are represented as same bifurcations in dynamical-systems theory, and this agreement of bifurcations lead to the evolution-development congruences. Violation of the evolution-development congruence, observed exceptionally, is shown to be originated in alteration of the boundary due to mutation at the upstream feedforward network. Our results provide a new look on developmental stages, punctuated equilibrium, developmental bottlenecks, and evolutionary acquisition of novelty in morphogenesis.

Search for possible relationships between phylogeny and ontogeny is one of the most important issues in the field of evolutionary developmental biology. By representing developmental dynamics of spatially located cells with gene expression dynamics with cell-to-cell interaction under external morphogen gradient, evolved are gene regulation networks under mutation and selection with the fitness to approach a prescribed spatial pattern of expressed genes. For most of thousands of numerical evolution experiments, evolution of pattern over generations and development of pattern by an evolved network exhibit remarkable congruence. Here, both the pattern dynamics consist of several epochs to form successive stripe formations between quasi-stationary regimes. In evolution, the regimes are generations needed to hit relevant mutations, while in development, they are due to the emergence of slowly varying expression that controls the pattern change. Successive pattern changes are thus generated, which are regulated by successive combinations of feedback or feedforward regulations under the upstream feedforward network that reads the morphogen gradient. By using a pattern generated by the upstream feedforward network as a boundary condition, downstream networks form later stripe patterns. These epochal changes in development and evolution are represented as same bifurcations in dynamical-systems theory, and this agreement of bifurcations lead to the evolution-development congruences. Violation of the evolution-development congruence, observed exceptionally, is shown to be originated in alteration of the boundary due to mutation at the upstream feedforward network. Our results provide a new look on developmental stages, punctuated equilibrium, developmental bottlenecks, and evolutionary acquisition of novelty in morphogenesis.

Search for possible relationships between phylogeny and ontogeny is one of the most important issues in the field of evolutionary developmental biology. By representing developmental dynamics of spatially located cells with gene expression dynamics with cell-to-cell interaction under external morphogen gradient, evolved are gene regulation networks under mutation and selection with the fitness to approach a prescribed spatial pattern of expressed genes. For most of thousands of numerical evolution experiments, evolution of pattern over generations and development of pattern by an evolved network exhibit remarkable congruence. Here, both the pattern dynamics consist of several epochs to form successive stripe formations between quasi-stationary regimes. In evolution, the regimes are generations needed to hit relevant mutations, while in development, they are due to the emergence of slowly varying expression that controls the pattern change. Successive pattern changes are thus generated, which are regulated by successive combinations of feedback or feedforward regulations under the upstream feedforward network that reads the morphogen gradient. By using a pattern generated by the upstream feedforward network as a boundary condition, downstream networks form later stripe patterns. These epochal changes in development and evolution are represented as same bifurcations in dynamical-systems theory, and this agreement of bifurcations lead to the evolution-development congruences. Violation of the evolution-development congruence, observed exceptionally, is shown to be originated in alteration of the boundary due to mutation at the upstream feedforward network. Our results provide a new look on developmental stages, punctuated equilibrium, developmental bottlenecks, and evolutionary acquisition of novelty in morphogenesis.

This article is focused on the study of a convection problem in a 2D set-up in the presence of the O(2) symmetry. In the fluid, viscosity depends on the temperature by changing its value abruptly in an interval around a temperature of transition. We explore the morphology of the plumes for several parameter settings in the viscosity law and perform bifurcation studies at several aspect ratios. We report that at a large aspect ratio and high Rayleigh numbers, travelling waves, heteroclinic connections and chaotic regimes are found, which are greatly influenced by the presence of the symmetry.

In this work we analyze PT-symmetric double-well potentials based on a two-mode picture. We reduce the problem into a PT-symmetric dimer and illustrate that the latter has effectively two fundamental bifurcations, a pitchfork (symmetry-breaking bifurcation) and a saddle-center one, which is the nonlinear analog of the PT-phase-transition. It is shown that the symmetry breaking leads to ghost states (amounting to growth or decay); although these states are not true solutions of the original continuum problem, the system's dynamics closely follows them, at least in its metastable evolution. Past the second bifurcation, there are no longer states of the original continuum system. Nevertheless, the solutions can be analytically continued to yield a new pair of branches, which is also identified and dynamically examined. Our explicit analytical results for the dimer are directly compared to the full continuum problem, yielding a good agreement.

We study fully three-dimensional droplets that slide down an incline by employing a thin-film equation that accounts for capillarity, wettability, and a lateral driving force in small-gradient (or long-wave) approximation. In particular, we focus on qualitative changes in the morphology and behavior of stationary sliding drops. We employ the inclination angle of the substrate as control parameter and use continuation techniques to analyze for several fixed droplet sizes the bifurcation diagram of stationary droplets, their linear stability, and relevant eigenmodes. The obtained predictions on existence ranges and instabilities are tested via direct numerical simulations that are also used to investigate a branch of time-periodic behavior (corresponding to repeated breakup-coalescence cycles, where the breakup is also denoted as pearling) which emerges at a global instability, the related hysteresis in behavior, and a period-doubling cascade. The nontrivial oscillatory behavior close to a Hopf bifurcation of drops with a finite-length tail is also studied. Finally, it is shown that the main features of the bifurcation diagram follow scaling laws over several decades of the droplet size.

We study fully three-dimensional droplets that slide down an incline by employing a thin-film equation that accounts for capillarity, wettability, and a lateral driving force in small-gradient (or long-wave) approximation. In particular, we focus on qualitative changes in the morphology and behavior of stationary sliding drops. We employ the inclination angle of the substrate as control parameter and use continuation techniques to analyze for several fixed droplet sizes the bifurcation diagram of stationary droplets, their linear stability, and relevant eigenmodes. The obtained predictions on existence ranges and instabilities are tested via direct numerical simulations that are also used to investigate a branch of time-periodic behavior (corresponding to repeated breakup-coalescence cycles, where the breakup is also denoted as pearling) which emerges at a global instability, the related hysteresis in behavior, and a period-doubling cascade. The nontrivial oscillatory behavior close to a Hopf bifurcation of drops with a finite-length tail is also studied. Finally, it is shown that the main features of the bifurcation diagram follow scaling laws over several decades of the droplet size.

It has been recently established that heterogeneous bootstrap percolation and related dynamic facilitation models exhibit a complex hierarchy of continuous and discontinuous transitions depending on lattice connectivity and kinetic constraints. Here the range of the previously observed phase diagram topologies and higher-order singularities is extended to disconnected glass-glass transitions and to cusp and swallowtail bifurcations (which can be generic and degenerate). The phase diagram and the order parameter for two different types of spin mixtures are analytically determined and an experimental realization of the new predictions emerging in our approach is suggested.

It has been recently established that heterogeneous bootstrap percolation and related dynamic facilitation models exhibit a complex hierarchy of continuous and discontinuous transitions depending on lattice connectivity and kinetic constraints. Here the range of the previously observed phase diagram topologies and higher-order singularities is extended to disconnected glass-glass transitions and to cusp and swallowtail bifurcations (which can be generic and degenerate). The phase diagram and the order parameter for two different types of spin mixtures are analytically determined and an experimental realization of the new predictions emerging in our approach is suggested.

This paper presents a mechanism for the coexistence of hyperbolic and non-hyperbolic dynamics arising in a neighbourhood of a conservative Bykov cycle where trajectories turn in opposite directions near the two saddle-foci. We show that {within the class of divergence-free vector fields that preserve the cycle,} tangencies of the invariant manifolds of two hyperbolic saddle-foci densely occur. The global dynamics is persistently dominated by heteroclinic tangencies and by the existence of infinitely many elliptic points coexisting with suspended hyperbolic horseshoes. A generalized version of the Cocoon bifurcations for conservative systems is obtained.

We study bifurcations of area-preserving maps, both orientable (symplectic) and non-orientable, with quadratic homoclinic tangencies. We consider one and two parameter general unfoldings and establish results related to the appearance of elliptic periodic orbits. In particular, we find conditions for such maps to have infinitely many generic (KAM-stable) elliptic periodic orbits of all successive periods starting at some number.

Bifurcations can cause dynamical systems with slowly varying parameters to transition to far-away attractors. The terms ``critical transition'' or ``tipping point'' have been used to describe this situation. Critical transitions have been observed in an astonishingly diverse set of applications from ecosystems and climate change to medicine and finance. The main goal of this paper is to give an overview which standard mathematical theories can be applied to critical transitions. We shall focus on early-warning signs that have been suggested to predict critical transitions and point out what mathematical theory can provide in this context. Starting from classical bifurcation theory and incorporating multiple time scale dynamics one can give a detailed analysis of local bifurcations that induce critical transitions. We suggest that the mathematical theory of fast-slow systems provides a natural definition of critical transitions. Since noise often plays a crucial role near critical transitions the next step is to consider stochastic fast-slow systems. The interplay between sample path techniques, partial differential equations and random dynamical systems is highlighted. Each viewpoint provides potential early-warning signs for critical transitions. Since increasing variance has been suggested as an early-warning sign we examine it in the context of normal forms analytically, numerically and geometrically; we also consider autocorrelation numerically. Hence we demonstrate the applicability of early-warning signs for generic models. We end with suggestions for future directions of the theory.

On infinitesimally short time interval various processes contributing to population change tend to operate independently so that we can simply add their contributions (Metz and Diekmann (1986)). This is one of the cornerstones for differential equations modeling in general. Complicated models for processes interacting in a complex manner may be built up, and not only in population dynamics. The principle holds as long as the various contributions are taken into account exactly. In this paper we discuss commonly used approximations that may lead to dependency terms affecting the long run qualitative behavior of the involved equations. We prove that these terms do not produce such effects in the simplest and most interesting biological case, but the general case is left open.

Talk by Dolores Bozovic, UCLA. Given to the Redwood Center for Theoretical Neuroscience at UC Berkeley. Abstract The inner ear constitutes a remarkable biological sensor that exhibits nanometer-scale sensitivity of mechanical detection. The first step in auditory processing is performed by hair cells, which convert movement into electrical signals via opening of mechanically gated ion channels. These cells are operant in a viscous medium, but can nevertheless sustain oscillations, amplify incoming signals, and even exhibit spontaneous motility, indicating the presence of an underlying active amplification system. Theoretical models have proposed that a hair cell constitutes a nonlinear system with an internal feedback mechanism that can drive it across a bifurcation and into an unstable regime. Our experiments explore the nonlinear response as well as feedback mechanisms that enable self-tuning already at the peripheral level, as measured in vitro on sensory tissue. A simple dynamic systems framework will be discussed, that captures the main features of the experimentally observed behavior in the form of an Arnold Tongue.

The singular bifurcations in a dispersive billiard are discussed in terms of symbolic dynamics and is compared to an example of a bifurcation tree in a smooth potential. Possible generalizations to other smooth potentials are discussed.

I present an organic description of the regimes of collisionless tidal streams and define the orderings between the physical quantities that shape their morphology. Three fundamental dichotomies are identified in the form of dimensionless inequalities. These govern i) the speed of the stream's growth, ii) its internal coherence, iii) its thickness or opening angles. The mechanisms that regulate such main properties are analysed. The slope of the host's density profile influences the speed of the stream's growth, in both length and width, as steeper profiles enhance differential streaming. Internal coherence is the requirement for the appearance of substructure in tidal debris, and I concentrate on the `feathering' typical of GC streams. Overdensities are associated with minima in the relative streaming velocity of the stream members. For streams with high circularity, these are caused by the epicyclic oscillations of stars; however, for highly non-circular progenitor's orbits, substructure is caused by the oscillating differences in energy and actions with which material is shed at different orbital phases of the progenitor. This modulation results in different streaming speeds: the streakline of material shed between two successive apocentric passages is folded along its length, pulled at its centre by the faster streaming of particles released near pericenter, which are therefore more widely scattered. When the stream is coherent enough, this mechanism is potentially capable of generating a bimodal profile in the density distributions of the longer wraps of more massive progenitors, which I dub `bifurcations'. The conditions for internal coherence are explored and I comment on the cases of Palomar 5, Willman 1, the Anticenter and Sagittarius' streams. Analytical methods are accompanied by numerical experiments, performed using a purposely built generative model, also presented here.