Parametric Sensitivity Analysis of the Most Recent Computational Models of Rabbit Cardiac Pacemaking

The cellular basis of cardiac pacemaking activity, and specifically the quantitative contributions of particular mechanisms, is still debated. Reliable computational models of sinoatrial nodal (SAN) cells may provide mechanistic insights, but competing models are built from different data sets and with different underlying assumptions. To understand quantitative differences between alternative models, we performed thorough parameter sensitivity analyses of the SAN models of Maltsev & Lakatta (2009) and Severi et al (2012). Model parameters were randomized to generate a population of cell models with different properties, simulations performed with each set of random parameters generated 14 quantitative outputs that characterized cellular activity, and regression methods were used to analyze the population behavior. Clear differences between the two models were observed at every step of the analysis. Specifically: (1) SR Ca2+ pump activity had a greater effect on SAN cell cycle length (CL) in the Maltsev model; (2) conversely, parameters describing the funny current (If) had a greater effect on CL in the Severi model; (3) changes in rapid delayed rectifier conductance (GKr) had opposite effects on action potential amplitude in the two models; (4) within the population, a greater percentage of model cells failed to exhibit action potentials in the Maltsev model (27%) compared with the Severi model (7%), implying greater robustness in the latter; (5) confirming this initial impression, bifurcation analyses indicated that smaller relative changes in GKr or Na+-K+ pump activity led to failed action potentials in the Maltsev model. Overall, the results suggest experimental tests that can distinguish between models and alternative hypotheses, and the analysis offers strategies for developing anti-arrhythmic pharmaceuticals by predicting their effect on the pacemaking activity.

Numerical and semi-analytical models of sliding masses: application to the 1783 Scilla tsunamigenic landslide

The Scilla rock avalanche occurred on 6 February 1783 along the coast of the Calabria region (southern Italy), close to the Messina Strait. It was triggered by a mainshock of the Terremoto delle Calabrie seismic sequence, and it induced a tsunami wave responsible for more than 1500 casualties along the neighboring Marina Grande beach. The main goal of this work is the application of semi-analtycal and numerical models to simulate this event. The first one is a MATLAB code expressly created for this work that solves the equations of motion for sliding particles on a two-dimensional surface through a fourth-order Runge-Kutta method. The second one is a code developed by the Tsunami Research Team of the Department of Physics and Astronomy (DIFA) of the Bologna University that describes a slide as a chain of blocks able to interact while sliding down over a slope and adopts a Lagrangian point of view. A wide description of landslide phenomena and in particular of landslides induced by earthquakes and with tsunamigenic potential is proposed in the first part of the work. Subsequently, the physical and mathematical background is presented; in particular, a detailed study on derivatives discratization is provided. Later on, a description of the dynamics of a point-mass sliding on a surface is proposed together with several applications of numerical and analytical models over ideal topographies. In the last part, the dynamics of points sliding on a surface and interacting with each other is proposed. Similarly, different application on an ideal topography are shown. Finally, the applications on the 1783 Scilla event are shown and discussed.

Action-based dynamical models of the Fornax dwarf spheroidal galaxy

Il lavoro presentato in questa Tesi si basa sul calcolo di modelli dinamici per Galassie Sferoidali Nane studiando il problema mediante l'utilizzo di funzioni di distribuzione. Si è trattato un tipo di funzioni di distribuzione, "Action-Based distribution functions", le quali sono funzioni delle sole variabili azione. Fornax è stata descritta con un'appropriata funzione di distribuzione e il problema della costruzione di modelli dinamici è stato affrontato assumendo sia un alone di materia oscura con distribuzione di densità costante nelle regioni interne sia un alone con cuspide. Per semplicità è stata assunta simmetria sferica e non è stato calcolato esplicitamente il potenziale gravitazionale della componente stellare (le stelle sono traccianti in un potenziale gravitazionale fissato). Tramite un diretto confronto con alcune osservabili, quali il profilo di densità stellare proiettata e il profilo di dispersione di velocità lungo la linea di vista, sono stati trovati alcuni modelli rappresentativi della dinamica di Fornax. Modelli calcolati tramite funzioni di distribuzione basati su azioni permettono di determinare in maniera autoconsistente profili di anisotropia. Tutti i modelli calcolati sono caratterizzati dal possedere un profilo di anisotropia con forte anisotropia tangenziale. Sono state poi comparate le stime di materia oscura di questi modelli con i più comuni e usati stimatori di massa in letteratura. E stato inoltre stimato il rapporto tra la massa totale del sistema (componente stellare e materia oscura) e la componente stellare di Fornax, entro 1600 pc ed entro i 3 kpc. Come esplorazione preliminare, in questo lavoro abbiamo anche presentato anche alcuni esempi di modelli sferici a due componenti in cui il campo gravitazionale è determinato dall'autogravità delle stelle e da un potenziale esterno che rappresenta l'alone di materia oscura.