Mathematical Modeling to Investigate Antiarrhythmic Drug Side Effects: Rate-Dependence Role in Ionic Currents and Action Potentials Shape in the O’Hara Model

Sudden cardiac death due to ventricular arrhythmia is one of the leading causes of mortality in the world. In the last decades, it has proven that anti-arrhythmic drugs, which prolong the refractory period by means of prolongation of the cardiac action potential duration (APD), play a good role in preventing of relevant human arrhythmias. However, it has long been observed that the “class III antiarrhythmic effect” diminish at faster heart rates and that this phenomenon represent a big weakness, since it is the precise situation when arrhythmias are most prone to occur. It is well known that mathematical modeling is a useful tool for investigating cardiac cell behavior. In the last 60 years, a multitude of cardiac models has been created; from the pioneering work of Hodgkin and Huxley (1952), who first described the ionic currents of the squid giant axon quantitatively, mathematical modeling has made great strides. The O’Hara model, that I employed in this research work, is one of the modern computational models of ventricular myocyte, a new generation began in 1991 with ventricular cell model by Noble et al. Successful of these models is that you can generate novel predictions, suggest experiments and provide a quantitative understanding of underlying mechanism. Obviously, the drawback is that they remain simple models, they don’t represent the real system. The overall goal of this research is to give an additional tool, through mathematical modeling, to understand the behavior of the main ionic currents involved during the action potential (AP), especially underlining the differences between slower and faster heart rates. In particular to evaluate the rate-dependence role on the action potential duration, to implement a new method for interpreting ionic currents behavior after a perturbation effect and to verify the validity of the work proposed by Antonio Zaza using an injected current as a perturbing effect.

Constraining mass and shape of galaxy clusters through large scale structures

The mass estimation of galaxy clusters is a crucial point for modern cosmology, and can be obtained by several different techniques. In this work we discuss a new method to measure the mass of galaxy clusters connecting the gravitational potential of the cluster with the kinematical properties of its surroundings. We explore the dynamics of the structures located in the region outside virialized cluster, We identify groups of galaxies, as sheets or filaments, in the cluster outer region, and model how the cluster gravitational potential perturbs the motion of these structures from the Hubble fow. This identification is done in the redshift space where we look for overdensities with a filamentary shape. Then we use a radial mean velocity profile that has been found as a quite universal trend in simulations, and we fit the radial infall velocity profile of the overdensities found. The method has been tested on several cluster-size haloes from cosmological N-body simulations giving results in very good agreement with the true values of virial masses of the haloes and orientation of the sheets. We then applied the method to the Coma cluster and even in this case we found a good correspondence with previous. It is possible to notice a mass discrepancy between sheets with different alignments respect to the center of the cluster. This difference can be used to reproduce the shape of the cluster, and to demonstrate that the spherical symmetry is not always a valid assumption. In fact, if the cluster is not spherical, sheets oriented along different axes should feel a slightly different gravitational potential, and so give different masses as result of the analysis described before. Even this estimation has been tested on cosmological simulations and then applied to Coma, showing the actual non-sphericity of this cluster.

Shape-based compliance control for snake robots

I serpenti robot sono una classe di meccanismi iper-ridondanti che appartiene alla robotica modulare. Grazie alla loro forma snella ed allungata e all'alto grado di ridondanza possono muoversi in ambienti complessi con elevata agilità. L'abilità di spostarsi, manipolare e adattarsi efficientemente ad una grande varietà di terreni li rende ideali per diverse applicazioni, come ad esempio attività di ricerca e soccorso, ispezione o ricognizione. I robot serpenti si muovono nello spazio modificando la propria forma, senza necessità di ulteriori dispositivi quali ruote od arti. Tali deformazioni, che consistono in movimenti ondulatori ciclici che generano uno spostamento dell'intero meccanismo, vengono definiti andature. La maggior parte di esse sono ispirate al mondo naturale, come lo strisciamento, il movimento laterale o il movimento a concertina, mentre altre sono create per applicazioni specifiche, come il rotolamento o l'arrampicamento. Un serpente robot con molti gradi di libertà deve essere capace di coordinare i propri giunti e reagire ad ostacoli in tempo reale per riuscire a muoversi efficacemente in ambienti complessi o non strutturati. Inoltre, aumentare la semplicità e ridurre il numero di controllori necessari alla locomozione alleggerise una struttura di controllo che potrebbe richiedere complessità per ulteriori attività specifiche. L'obiettivo di questa tesi è ottenere un comportamento autonomo cedevole che si adatti alla conformazione dell'ambiente in cui il robot si sta spostando, accrescendo le capacità di locomozione del serpente robot. Sfruttando la cedevolezza intrinseca del serpente robot utilizzato in questo lavoro, il SEA Snake, e utilizzando un controllo che combina cedevolezza attiva ad una struttura di coordinazione che ammette una decentralizzazione variabile del robot, si dimostra come tre andature possano essere modificate per ottenere una locomozione efficiente in ambienti complessi non noti a priori o non modellabili.

Pulse shape studies of neutral particles with a liquid scintillator

The hadrontherapy exploits beams of charged particles against deep cancers. These ions have a depth-dose profile in which there is a little release of energy at the beginning of their path, whereas there is a sharp maximum, the Bragg Peak, near its end path. However, if heavy ions are used, the fragmentation of the projectile can happen and the fragments can release some dose outside the treatment volume beyond the Bragg peak. The fragmentation process takes place also when the Galactic Cosmic Rays at high energy hit the spaceship during space missions. In both cases some neutrons can be produced and if they interact with the absorbing materials nuclei some secondary particles are generated which can release energy. For this reason, studies about the cross section measurements of the fragments generated during the collisions of heavy ions against the tissues nuclei are very important. In this context, the FragmentatiOn Of Target (FOOT) experiment was born, and aims at measuring the differential and double differential fragmentation cross sections for different kinetic energies relevant to hadrontherapy and space radioprotection with high accuracy. Since during fragmentation processes also neutrons are produced, tests of a neutron detection system are ongoing. In particular, recently a neutron detector made up of a liquid organic scintillator, BC-501A with neutrons/gammas discrimination capability was studied, and it represents the core of this thesis. More in details, an analysis of the data collected at the GSI laboratory, in Darmstadt, Germany, is effectuated which consists in discriminating neutral and charged particles and then to separate neutrons from gammas. From this analysis, a preliminary energy-differential reaction cross-section for the production of neutrons in the 16O + (C_2H_4)_(n) and 16O + C reactions was estimated.