Vesicle motion during sustained exocytosis in chromaffin cells

Chromaffin cells release catecholamines by exocytosis, a process that includes vesicle docking, priming and fusion. Although all these steps have been intensively studied, some aspects of their mechanisms, particularly those regarding vesicle transport to the active sites situated at the membrane, are still unclear. In this work, we show that it is possible to extract information on vesicle motion in Chromaffin cells from the combination of Langevin simulations and amperometric measurements. We developed a numerical model based on Langevin simulations of vesicle motion towards the cell membrane and on the statistical analysis of vesicle arrival times. We also performed amperometric experiments in bovine-adrenal Chromaffin cells under Ba2+ stimulation to capture neurotransmitter releases during sustained exocytosis. In the sustained phase, each amperometric peak can be related to a single release from a new vesicle arriving at the active site. The amperometric signal can then be mapped into a spike-series of release events. We normalized the spike-series resulting from the current peaks using a time-rescaling transformation, thus making signals coming from different cells comparable. We discuss why the obtained spike-series may contain information about the motion of all vesicles leading to release of catecholamines. We show that the release statistics in our experiments considerably deviate from Poisson processes. Moreover, the interspike-time probability is reasonably well described by two-parameter gamma distributions. In order to interpret this result we computed the vesicles’ arrival statistics from our Langevin simulations. As expected, assuming purely diffusive vesicle motion we obtain Poisson statistics. However, if we assume that all vesicles are guided toward the membrane by an attractive harmonic potential, simulations also lead to gamma distributions of the interspike-time probability, in remarkably good agreement with experiment. We also show that including the fusion-time statistics in our model does not produce any significant changes on the results. These findings indicate that the motion of the whole ensemble of vesicles towards the membrane is directed and reflected in the amperometric signals. Our results confirm the conclusions of previous imaging studies performed on single vesicles that vesicles’ motion underneath plasma membranes is not purely random, but biased towards the membrane.

An Immersed Interface Method for the Incompressible Navier-Stokes Equations in Irregular Domains

We present an immersed interface method for the incompressible Navier Stokes equations capable of handling rigid immersed boundaries. The immersed boundary is represented by a set of Lagrangian control points. In order to guarantee that the no-slip condition on the boundary is satisfied, singular forces are applied on the fluid at the immersed boundary. The forces are related to the jumps in pressure and the jumps in the derivatives of both pressure and velocity, and are interpolated using cubic splines. The strength of singular forces is determined by solving a small system of equations at each time step. The Navier-Stokes equations are discretized on a staggered Cartesian grid by a second order accurate projection method for pressure and velocity.

Temporary and Permanent Buyout Prices in Online Auctions

Increasingly used in online auctions, buyout prices allow bidders to instantly purchase the item listed. We distinguish two types: a temporary buyout option disappears if a bid above the reserve price is made; a permanent one remains throughout the auction or until it is exercised. In a model featuring time-sensitive bidders with uniform valuations and Poisson arrivals but endogenous bidding times, we focus on finding temporary and permanent buyout prices maximizing the seller's discounted revenue, and examine the relative benefit of using each type of option in various environments. We characterize equilibrium bidder strategies in both cases and then solve the problem of maximizing seller's utility by simulation. Our numerical experiments suggest that buyout options may significantly increase a seller’s revenue. Additionally, while a temporary buyout option promotes early bidding, a permanent option gives an incentive to the bidders to bid late, thus leading to concentrated bids near the end of the auction.

Discrete and continuous compositions

This paper examines a dataset which is modeled well by the Poisson-Log Normal process and by this process mixed with Log Normal data, which are both turned into compositions. This generates compositional data that has zeros without any need for conditional models or assuming that there is missing or censored data that needs adjustment. It also enables us to model dependence on covariates and within the composition

Uso de modelos econométricos en aseguramiento de portafolios

El aseguramiento de portafolio trae consigo unos costos de transacción asociados que son reconocidos por la teoría financiera pero que no han sido objeto de estudio de muchas aproximaciones empíricas. Mediante modelos econométricos de series de tiempo se puede pronosticar el número de rebalanceos necesarios para mantener un portafolio asegurado, así como el tiempo que debe transcurrir entre cada uno de estos. Para tal fin se usan modelos de Datos de Cuenta de Poisson Autorregresivos (ACP) modificados para captar las características de la serie y modelos de Duración Autorregresivos (ACD). Los modelos capturan la autocorrelación de las series y pronostican adecuadamente el costo de transacción asociado a los rebalanceos.

Modelo tridimensional del tendón del músculo supraespinoso

Introducción: Teniendo en cuenta el envejecimiento de la población y la alta prevalencia de las lesiones del manguito rotador no es de extrañar que esta patología se convierta en un problema de salud pública. Se sabe que el aumento en el tamaño de una lesión se asocia con la aparición de síntomas, pero no existen herramientas que permitan predecir la evolución del tamaño de una lesión. Con esto en mente se desarrollo una línea de investigación para estudiar el mecanismo de falla que inicia con la realización de un modelo tridimensional de un tendón del musculo supraespinoso sano. Materiales y métodos: Se caracterizo el tendón del músculo supraespinoso aplicando cargas uniaxiales a 7 complejos humero-tendón-escápula cadavéricos. Con los datos obtenidos se alimento un modelo tridimensional lineal isotrópico analizando la concentración de esfuerzos de von Misses Resultados: Del ensayo uniaxial se obtuvieron curvas esfuerzo-deformación homogéneas para el 20% de la deformación inicial, obteniendo un modulo de Young (14.4±2.3MPa) y un coeficiente de Poisson (0.14) con una concentración de esfuerzos de en la zona central de la cara articular del tendón, cercana a su inserción. Encontramos una disminución del 5% en los esfuerzos al retirar el acromion del modelo. Conclusiones: Se caracterizó de manera exitosa y se obtuvo un modelo tridimensional del tendón. La distribución de esfuerzos es compatible con la reportada en la literatura. El acromion no tiene mayor importancia en la magnitud de los esfuerzos en nuestro modelo. Este es el punto de partida para estudiar el mecanismo de falla.

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