RESUMEN

New compounds with promising antidiabetic activity were synthesized. For the first time, a portion of the glibenclamide molecule was bound to a part of the core structure of thiazolidinedione to evaluate insulin secretagogue activity. Following studies in our laboratory, 4-{2-[2-(3,4-dichlorophenyl)-4-oxo-1,3-thiazolidin-3-yl]ethyl}benzene-1-sulfonamide (DTEBS) was selected to evaluate glycemia using the glucose tolerance test and insulin secretagogue activity by E.L.I.S.A. The mechanism of action of this compound was studied by 45 Ca2+ influx and whole-cell patch-clamp in rat pancreatic isolated islets. Furthermore, AGE formation in vitro was investigated. We herein show that this novel hybrid compound (DTEBS) exhibits an insulinogenic index and a profile of serum insulin secretion able to maintain glucose homeostasis. Its mechanism of action is mediated by ATP-sensitive potassium channels (KATP) and L-type voltage-dependent calcium channels (VDCC) and by activating protein kinase C and A (PKC and PKA). In addition, the stimulatory action of the compound on calcium influx and insulin secretion indicates that the potentiation of voltage-sensitive K+ currents (Kv) is due to the repolarization phase of the action potential after secretagogue excitation-secretion in pancreatic islets. Furthermore, under these experimental conditions, the compound did not induce toxicity and the in vitro late response of the compound to protein glycation reinforces its use to prevent complications of diabetes. DTEBS exerts an insulin secretagogue effect by triggering KATP, VDCC, and Kv ionic currents, possibly via PKC and PKA pathway signal transduction, in beta-cells. Furthermore, DTEBS may hold potential for delaying the late complications of diabetes.

Asunto(s)

Hipoglucemiantes/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Compuestos de Sulfonilurea/farmacología , Animales , Calcio/metabolismo , Canales de Calcio Tipo L/genética , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Ensayo de Inmunoadsorción Enzimática , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Gliburida/química , Gliburida/farmacología , Humanos , Hipoglucemiantes/síntesis química , Insulina/biosíntesis , Secreción de Insulina/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Canales KATP/genética , Técnicas de Placa-Clamp , Proteína Quinasa C/genética , Ratas , Transducción de Señal/efectos de los fármacos , Compuestos de Sulfonilurea/síntesis química , Tiazolidinedionas/síntesis química , Tiazolidinedionas/farmacología

RESUMEN

The description of diffusion processes is possible in different frameworks such as random walks or Fokker-Planck or Langevin equations. Whereas for classical diffusion the equivalence of these methods is well established, in the case of anomalous diffusion it often remains an open problem. In this paper we aim to bring three approaches describing anomalous superdiffusive behavior to a common footing. While each method clearly has its advantages it is crucial to understand how those methods relate and complement each other. In particular, by using the method of subordination, we show how the Langevin equation can describe anomalous diffusion exhibited by Lévy-walk-type models and further show the equivalence of the random walk models and the generalized Kramers-Fokker-Planck equation. As a result a synergetic and complementary description of anomalous diffusion is obtained which provides a much more flexible tool for applications in real-world systems.

Asunto(s)

Biofisica/métodos , Algoritmos , Animales , Difusión , Células Epiteliales/metabolismo , Modelos Químicos , Modelos Estadísticos , Modelos Teóricos , Movimiento , Reproducibilidad de los Resultados

RESUMEN

We introduce a population model for species under cyclic competition. This model allows individuals to coexist and interact on single cells while migration takes place between adjacent cells. In contrast to the model introduced by Reichenbach, Mobilia, and Frey [Reichenbach, Mobilia, and Frey, Nature (London) 448, 1046 (2007)], we find that the emergence of spirals results in an ambiguous behavior regarding the stability of coexistence. The typical time until extinction exhibits, however, a qualitatively opposite dependence on the newly introduced nonunit carrying capacity in the spiraling and the nonspiraling regimes. This allows us to determine a critical mobility that marks the onset of this spiraling state sharply. In contrast, we demonstrate that the conventional finite size stability analysis with respect to spatial size is of limited use for identifying the onset of the spiraling regime.

Asunto(s)

Modelos Teóricos , Densidad de Población , Dinámica Poblacional

RESUMEN

In mesoscopic systems, conductance fluctuations are a sensitive probe of electron dynamics and chaotic phenomena. We show that the conductance of a purely classical chaotic system, with either fully chaotic or mixed phase space, generically exhibits fractal conductance fluctuations unrelated to quantum interference. This might explain the unexpected dependence of the fractal dimension of the conductance curves on the (quantum) phase breaking length observed in experiments on semiconductor quantum dots.

RESUMEN

The dynamic spatial redistribution of individuals is a key driving force of various spatiotemporal phenomena on geographical scales. It can synchronize populations of interacting species, stabilize them, and diversify gene pools. Human travel, for example, is responsible for the geographical spread of human infectious disease. In the light of increasing international trade, intensified human mobility and the imminent threat of an influenza A epidemic, the knowledge of dynamical and statistical properties of human travel is of fundamental importance. Despite its crucial role, a quantitative assessment of these properties on geographical scales remains elusive, and the assumption that humans disperse diffusively still prevails in models. Here we report on a solid and quantitative assessment of human travelling statistics by analysing the circulation of bank notes in the United States. Using a comprehensive data set of over a million individual displacements, we find that dispersal is anomalous in two ways. First, the distribution of travelling distances decays as a power law, indicating that trajectories of bank notes are reminiscent of scale-free random walks known as Lévy flights. Second, the probability of remaining in a small, spatially confined region for a time T is dominated by algebraically long tails that attenuate the superdiffusive spread. We show that human travelling behaviour can be described mathematically on many spatiotemporal scales by a two-parameter continuous-time random walk model to a surprising accuracy, and conclude that human travel on geographical scales is an ambivalent and effectively superdiffusive process.

Asunto(s)

Locomoción , Modelos Teóricos , Movimiento , Viaje , Difusión , Transmisión de Enfermedad Infecciosa , Economía , Humanos , Gripe Humana/epidemiología , Gripe Humana/transmisión , Estados Unidos

RESUMEN

The result of computational operations performed at the single cell level are coded into sequences of action potentials (APs). In the cerebral cortex, due to its columnar organization, large number of neurons are involved in any individual processing task. It is therefore important to understand how the properties of coding at the level of neuronal populations are determined by the dynamics of single neuron AP generation. Here, we analyze how the AP generating mechanism determines the speed with which an ensemble of neurons can represent transient stochastic input signals. We analyze a generalization of the theta-neuron, the normal form of the dynamics of Type-I excitable membranes. Using a novel sparse matrix representation of the Fokker-Planck equation, which describes the ensemble dynamics, we calculate the transmission functions for small modulations of the mean current and noise noise amplitude. In the high-frequency limit the transmission function decays as omega(-gamma), where gamma surprisingly depends on the phase theta(s) at which APs are emitted. If at theta(s) the dynamics is insensitive to external inputs, the transmission function decays as (i) omega(-3) for the case of a modulation of a white noise input and as (ii) omega(-2) for a modulation of the mean input current in the presence of a correlated and uncorrelated noise as well as (iii) in the case of a modulated amplitude of a correlated noise input. If the insensitivity condition is lifted, the transmission function always decays as omega(-1), as in conductance based neuron models. In a physiologically plausible regime up to 1 kHz the typical response speed is, however, independent of the high-frequency limit and is set by the rapidness of the AP onset, as revealed by the full transmission function. In this regime modulations of the noise amplitude can be transmitted faithfully up to much higher frequencies than modulations in the mean input current. We finally show that the linear response approach used is valid for a large regime of stimulus amplitudes.

Asunto(s)

Potenciales de Acción/fisiología , Corteza Cerebral/citología , Neuronas/fisiología , Dinámicas no Lineales , Animales , Modelos Neurológicos , Neuronas/clasificación , Procesos Estocásticos , Transmisión Sináptica/fisiología , Factores de Tiempo

RESUMEN

The rapid worldwide spread of severe acute respiratory syndrome demonstrated the potential threat an infectious disease poses in a closely interconnected and interdependent world. Here we introduce a probabilistic model that describes the worldwide spread of infectious diseases and demonstrate that a forecast of the geographical spread of epidemics is indeed possible. This model combines a stochastic local infection dynamics among individuals with stochastic transport in a worldwide network, taking into account national and international civil aviation traffic. Our simulations of the severe acute respiratory syndrome outbreak are in surprisingly good agreement with published case reports. We show that the high degree of predictability is caused by the strong heterogeneity of the network. Our model can be used to predict the worldwide spread of future infectious diseases and to identify endangered regions in advance. The performance of different control strategies is analyzed, and our simulations show that a quick and focused reaction is essential to inhibiting the global spread of epidemics.

Asunto(s)

Brotes de Enfermedades/prevención & control , Medicina Aeroespacial , Biometría , Control de Enfermedades Transmisibles , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/transmisión , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/prevención & control , Enfermedades Transmisibles Emergentes/transmisión , Brotes de Enfermedades/estadística & datos numéricos , Predicción , Humanos , Modelos Biológicos , Modelos Estadísticos , Síndrome Respiratorio Agudo Grave/epidemiología , Síndrome Respiratorio Agudo Grave/prevención & control , Síndrome Respiratorio Agudo Grave/transmisión , Procesos Estocásticos , Viaje

RESUMEN

We investigate the dynamics of a particle moving randomly along a disordered heteropolymer subjected to rapid conformational changes which induce superdiffusive motion in chemical coordinates. We study the antagonistic interplay between the enhanced diffusion and the quenched disorder. The dispersion speed exhibits universal behavior independent of the folding statistics. On the other hand it is strongly affected by the structure of the disordered potential. The results may serve as a reference point for a number of translocation phenomena observed in biological cells, such as protein dynamics on DNA strands.

Asunto(s)

Biopolímeros/química , Modelos Teóricos , ADN/metabolismo , Modelos Químicos , Conformación Molecular , Proteínas/metabolismo

RESUMEN

We investigate the impact of external periodic potentials on superdiffusive random walks known as Lévy flights and show that even strongly superdiffusive transport is substantially affected by the external field. Unlike ordinary random walks, Lévy flights are surprisingly sensitive to the shape of the potential while their asymptotic behavior ceases to depend on the Lévy index mu. Our analysis is based on a novel generalization of the Fokker-Planck equation suitable for systems in thermal equilibrium. Thus, the results presented are applicable to the large class of situations in which superdiffusion is caused by topological complexity, such as diffusion on folded polymers and scale-free networks.

RESUMEN

During ontogenetic development, the visual cortical circuitry is remodeled by activity-dependent mechanisms of synaptic plasticity. From a dynamical systems perspective this is a process of dynamic pattern formation. The emerging cortical network supports functional activity patterns that are used to guide the further improvement of the network's structure. In this picture, spontaneous symmetry breaking in the developmental dynamics of the cortical network underlies the emergence of cortical selectivities such as orientation preference. Here universal properties of this process depending only on basic biological symmetries of the cortical network are analyzed. In particular, we discuss the description of the development of orientation preference columns in terms of a dynamics of abstract order parameter fields, connect this description to the theory of Gaussian random fields, and show how the theory of Gaussian random fields can be used to obtain quantitative information on the generation and motion of pinwheels, in the two dimensional pattern of visual cortical orientation columns.

Asunto(s)

Reconocimiento Visual de Modelos/fisiología , Estimulación Luminosa/métodos , Corteza Visual/fisiología , Animales , Humanos

RESUMEN

We investigate the statistics of eigenfunction intensities P(/psi/(2)) in dynamical systems with classical chaotic diffusion. Our results contradict some recent theoretical considerations that challenge the applicability of field theoretical predictions, derived in a different framework for diffusive disordered samples. For two-dimensional systems, the tails of P(/psi/(2)) contradict the results of the optimal fluctuation method, but agree very well with the predictions of the nonlinear sigma model.

RESUMEN

We demonstrate for various systems that the variance of a wave packet M(t) proportional to t(nu), can show a superballistic increase with 2 < nu < or = 3, for parametrically large time intervals. A model is constructed that explains this phenomenon and its predictions are verified numerically for various disordered and quasiperiodic systems.

RESUMEN

The effect of impurities in a two-dimensional lattice of coupled nonlinear chaotic oscillators and their ability to control the dynamical behavior of the system are studied. We show that a single impurity can produce synchronized spatiotemporal patterns, even though all oscillators and the impurity are chaotic when uncoupled. When a small number of impurities is arranged in a way, that the lattice is divided into two disjoint parts, synchronization is enforced even for small coupling. The synchronization is not affected as the size of the lattice increases, although the impurity concentration tends to zero.

RESUMEN

The paradigm of stochastic resonance (SR)-the idea that signal detection and transmission may benefit from noise-has met with great interest in both physics and the neurosciences. We investigate here the consequences of reducing the dynamics of a periodically driven neuron to a renewal process (stimulation with reset or endogenous stimulation). This greatly simplifies the mathematical analysis, but we show that stochastic resonance as reported earlier occurs in this model only as a consequence of the reduced dynamics.

Asunto(s)

Potenciales de Acción/fisiología , Umbral Diferencial/fisiología , Potenciales de la Membrana/fisiología , Modelos Neurológicos , Modelos Estadísticos , Neuronas/fisiología , Procesos Estocásticos , Transmisión Sináptica/fisiología , Adaptación Fisiológica/fisiología , Simulación por Computador , Estimulación Eléctrica

RESUMEN

We study the distributions of the resonance widths P(gamma) and of delay times P(tau) in one-dimensional quasiperiodic tight-binding systems at critical conditions with one open channel. Both quantities are found to decay algebraically as gamma(-alpha) and tau(-gamma) on small and large scales, respectively. The exponents alpha and gamma are related to the fractal dimension D(E)(0) of the spectrum of the closed system as alpha = 1+D(E)(0) and gamma = 2-D(E)(0). Our results are verified for the Harper model at the metal-insulator transition and for Fibonacci lattices.

RESUMEN

We find that a 2D periodic potential, with different modulation amplitudes in the x and y directions, and a perpendicular magnetic field may lead to a transition to electron transport along the direction of stronger modulation and to localization in the direction of weaker modulation. In the experimentally accessible regime we relate this new quantum transport phenomenon to avoided band crossings due to classical chaos.

RESUMEN

The pattern of ocular dominance columns in primary visual cortex of mammals such as cats and macaque monkeys arises during development by the activity-dependent refinement of thalamocortical connections. Manipulating visual experience in kittens by the induction of squint leads to the emergence of ocular dominance columns with a larger size and larger column-to-column spacing than in normally raised animals. The mechanism underlying this phenomenon is presently unknown. Theory suggests that experience cannot influence the spacing of columns if the development proceeds through purely Hebbian mechanisms. Here we study a developmental model in which Hebbian mechanisms are complemented by activity-dependent regulation of the total strength of afferent synapses converging onto a cortical neurone. We show that this model implies an influence of visual experience on the spacing of ocular dominance columns and provides a conceptually simple explanation for the emergence of larger sized columns in squinting animals. Assuming that during development cortical neurones become active in local groups, which we call co-activated cortical domains (CCDs), ocular dominance segregation is controlled by the size of these groups: (1) Size and spacing of ocular dominance columns are proportional to the size sigma of CCDs. (2) There is a critical size sigma* of CCDs such that ocular dominance columns form if sigmasigma*. This critical size of CCDs is determined by the correlation functions of activity patterns in the two eyes and specifies the influence of experience on ocular dominance segregation. We show that sigma* is larger with squint than with normal visual experience. Since experimental evidence indicates that the size of CCDs decreases during development, ocular dominance columns are predicted to form earlier and with a larger spacing in squinters compared to normal animals.

Asunto(s)

Dominancia Cerebral/fisiología , Neuronas/fisiología , Estrabismo , Corteza Visual/fisiología , Animales , Gatos , Corteza Cerebral/fisiología , Convergencia Ocular , Lateralidad Funcional , Humanos , Mamíferos , Sinapsis/fisiología , Tálamo/fisiología

RESUMEN

We investigate a general and analytically tractable model for the activity-dependent formation of neuronal connectivity patterns. Previous models are contained as limiting cases. As an important example we analyze the formation of ocular dominance patterns in the visual cortex. A linear stability analysis reveals that the model undergoes a Turing-type instability as a function of interaction range and receptive field size. The phase transitions is of second order. After the linear instability the patterns may reorganize which we analyze in terms of a potential for the dynamics. Our analysis demonstrates that the experimentally observed dependency of ocular dominance patterns on interocular correlations of visual experience during development can emerge according to two generic scenarios: either the system is driven through the phase transition during development thereby selecting and stabilizing the first unstable mode or a primary pattern reorganizes towards larger wavelength according their lower energy. Experimentally observing the time course of ocular dominance pattern formation will decide which scenario is realized in the brain.

Asunto(s)

Dominancia Cerebral , Fenómenos Fisiológicos Oculares , Algoritmos , Animales , Encéfalo/fisiología , Gatos , Simulación por Computador , Modelos Estadísticos , Neuronas/fisiología , Factores de Tiempo , Corteza Visual/fisiología

RESUMEN

We model the dynamics of the leaky integrate-and-fire neuron under periodic stimulation as a Markov process with respect to the stimulus phase. This avoids the unrealistic assumption of a stimulus reset after each spike made in earlier papers and thus solves the long-standing reset problem. The neuron exhibits stochastic resonance, both with respect to input noise intensity and stimulus frequency. The latter resonance arises by matching the stimulus frequency to the refractory time of the neuron. The Markov approach can be generalized to other periodically driven stochastic processes containing a reset mechanism.

Asunto(s)

Biofisica , Cadenas de Markov , Neuronas/metabolismo , Neuronas/fisiología , Procesos Estocásticos , Animales , Fenómenos Biofísicos , Modelos Estadísticos , Distribución Normal

RESUMEN

Neurons in the visual cortex respond preferentially to edge-like stimuli of a particular orientation. It is a long-standing hypothesis that orientation selectivity arises during development through the activity-dependent refinement of cortical circuitry. Unambiguous evidence for such a process has, however, remained elusive. Here we argue that, if orientation preferences arise through activity-dependent refinement of initially unselective patterns of synaptic connections, this process should leave distinct signatures in the emerging spatial pattern of preferred orientations. Preferred orientations typically change smoothly and progressively across the cortex. This smooth progression is disrupted at the centres of so-called pinwheels, where neurons exhibiting the whole range of orientation preferences are located in close vicinity. Assuming that orientation selectivity develops through a set of rules that we do not specify, we demonstrate mathematically that the spatial density of pinwheels is rigidly constrained by basic symmetry principles. In particular, the spatial density of pinwheels, which emerge when orientation selectivity is first established, is larger than a model-independent minimal value. As a consequence, lower densities, if observed in adult animals, are predicted to develop through the motion and annihilation of pinwheel pairs.

Asunto(s)

Neuronas/fisiología , Visión Ocular/fisiología , Corteza Visual/anatomía & histología , Corteza Visual/embriología , Modelos Biológicos , Sinapsis