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.

Accelerated ageing methodologies for the evaluation of particulate matter role in the corrosion of outdoor-exposed bronzes

Deterioration phenomena occurring on outdoor cultural heritage have been the subject of several studies, but relatively few works investigated the specific role of Particulate Matter (PM) in the corrosion of metals. This topic is really complex and, besides field exposures, accelerated ageing tests are also necessary to isolate and understand deterioration mechanisms due to PM. For this reason, the development of a methodology that allows to reproduce and analyze the effect of PM on alloys through accelerated ageing in climatic chamber has been started. On quaternary bronze specimens, single salts and a mix of them were deposited via two deposition methods: dry (directly depositing the salt on the surface) and wet (dropping a salt solution and drying it), simulating the initial chemical activation of the salts by RH% variations or by raindrops, respectively. Then, to better mimic the composition of real PM, a mixture containing a soluble salts, a mineral, a black carbon and an organic fraction was formulated and spread on the samples. The samples were placed in a climatic chamber and exposed to cyclic variations of T and RH for three weeks. The ageing cycles were set according to predictions on salt deliquescence/recrystallization through E-AIM model and to the evaluation of regional climatic data. The surface evolution was followed by SEM-EDX, Raman, AT-IR and UV-Vis Spectrophotometry. At the end of the test, mass losses were determined and corroded metals removed by pickling were analyzed by AAS. On the basis of the obtained results, the tested procedures seem to be promising in accelerating and mimicking realistic corrosion phenomena, as under the selected conditions, corrosion products typically found at different exposure time (from days to years) on outdoor bronzes were able to progressively form and evolve. Moreover, the two deposition modes simulating different condition of chemical activation of PM deposits allow to obtain complementary information.

Studio geomorfologico dell'area carsica attorno alla Grotta Palombara (Melilli, Siracusa)

The following thesis attempts to study and analyse the geomorphological evolution of a relatively small coastal area located to the North of Syracuse (Southeastern Sicily). The presently inactive Palombara Cave is located in this area. The 800 metres of passages in this cave show an evolution in some way linked to the local topographic and environmental changes. This portion of coastline was affected more or less constantly by the tectonic uplift during the Pleistocene, which simultaneously to the eustatic variations have played a key role in the genesis of the marine terraces and the cave. Starting from a DTM made from Lidar data, using a GIS procedure several marine terraces have been mapped. These informations combinated with a geomorphological study of the area, allowed to identify and recognise the different orders of the Middle Pleistocene terraced surfaces. Four orders of terraces between 180-75 m a.s.l have been observed, illustrated and described. Furthermore, two other supposed terrace edges located respectively at 60 and 35 m, which would indicate the presence of two more orders, have been recognised. All these marine terraces appear to have formed in the last million years. The morphological data of the Palombara cave, highlights a genesis related to the rising of CO2 rich waters coming from the depths through the fractures of the rock mass, that ranks it as a hypogenic cave. The development has been influenced by the changes in the water table, in turn determined by the fluctuations in the sea level. In fact, the cave shows a speleogenetic evolution characterised by phases of karstification in phreatic and epiphreatic environment and fossilization stages of the upper branches in vadose conditions. These observations indicate that the cave probably started forming around 600 Ky ago, contemporary to the start of volcanic processes in the area.