Air pollution and health: bridging the gap from sources to health outcomes: conference summary

Air Pollution and Health: Bridging the Gap from Sources to Health Outcomes, an international specialty conference sponsored by the American Association for Aerosol Research, was held to address key uncertainties in our understanding of adverse health effects related to air pollution and to integrate and disseminate results from recent scientific studies that cut across a range of air pollution-related disciplines. The Conference addressed the science of air pollution and health within a multipollutant framework (herein "multipollutant" refers to gases and particulate matter mass, components, and physical properties), focusing on five key science areas: sources, atmospheric sciences, exposure, dose, and health effects. Eight key policy-relevant science questions integrated across various parts of the five science areas and a ninth question regarding findings that provide policy-relevant insights served as the framework for the meeting. Results synthesized from this Conference provide new evidence, reaffirm past findings, and offer guidance for future research efforts that will continue to incrementally advance the science required for reducing uncertainties in linking sources, air pollutants, human exposure, and health effects. This paper summarizes the Conference findings organized around the science questions. A number of key points emerged from the Conference findings. First, there is a need for greater focus on multipollutant science and management approaches that include more direct studies of the mixture of pollutants from sources with an emphasis on health studies at ambient concentrations. Further, a number of research groups reaffirmed a need for better understanding of biological mechanisms and apparent associations of various health effects with components of particulate matter (PM), such as elemental carbon, certain organic species, ultrafine particles, and certain trace elements such as Ni, V, and Fe(II), as well as some gaseous pollutants. Although much debate continues in this area, generation of reactive oxygen species induced by these and other species present in air pollution and the resulting oxidative stress and inflammation were reiterated as key pathways leading to respiratory and cardiovascular outcomes. The Conference also underscored significant advances in understanding the susceptibility of populations, including the role of genetics and epigenetics and the influence of socioeconomic and other confounding factors and their synergistic interactions with air pollutants. Participants also pointed out that short-and long-term intervention episodes that reduce pollution from sources and improve air quality continue to indicate that when pollution decreases so do reported adverse health effects. In the limited number of cases where specific sources or PM2.5 species were included in investigations, specific species are often associated with the decrease in effects. Other recent advances for improved exposure estimates for epidemiological studies included using new technologies such as microsensors combined with cell phone and integrated into real-time communications, hybrid air quality modeling such as combined receptor-and emission-based models, and surface observations used with remote sensing such as satellite data.

An in-depth analysis of the HIV-1/AIDS dynamics by comprehensive mathematical modeling

This work presents major results from a novel dynamic model intended to deterministically represent the complex relation between HIV-1 and the human immune system. The novel structure of the model extends previous work by representing different host anatomic compartments under a more in-depth cellular and molecular immunological phenomenology. Recently identified mechanisms related to HIV-1 infection as well as other well known relevant mechanisms typically ignored in mathematical models of HIV-1 pathogenesis and immunology, such as cell-cell transmission, are also addressed. (C) 2011 Elsevier Ltd. All rights reserved.

Towards the construction of a validated numerical system to study the mesoscale dynamics of the North East Atlantic (2003-2006)

Máster en Oceanografía

Computational analyses on the structure-function relation in ion channels

Ion channels are protein molecules, embedded in the lipid bilayer of the cell membranes. They act as powerful sensing elements switching chemicalphysical stimuli into ion-fluxes. At a glance, ion channels are water-filled pores, which can open and close in response to different stimuli (gating), and one once open select the permeating ion species (selectivity). They play a crucial role in several physiological functions, like nerve transmission, muscular contraction, and secretion. Besides, ion channels can be used in technological applications for different purpose (sensing of organic molecules, DNA sequencing). As a result, there is remarkable interest in understanding the molecular determinants of the channel functioning. Nowadays, both the functional and the structural characteristics of ion channels can be experimentally solved. The purpose of this thesis was to investigate the structure-function relation in ion channels, by computational techniques. Most of the analyses focused on the mechanisms of ion conduction, and the numerical methodologies to compute the channel conductance. The standard techniques for atomistic simulation of complex molecular systems (Molecular Dynamics) cannot be routinely used to calculate ion fluxes in membrane channels, because of the high computational resources needed. The main step forward of the PhD research activity was the development of a computational algorithm for the calculation of ion fluxes in protein channels. The algorithm - based on the electrodiffusion theory - is computational inexpensive, and was used for an extensive analysis on the molecular determinants of the channel conductance. The first record of ion-fluxes through a single protein channel dates back to 1976, and since then measuring the single channel conductance has become a standard experimental procedure. Chapter 1 introduces ion channels, and the experimental techniques used to measure the channel currents. The abundance of functional data (channel currents) does not match with an equal abundance of structural data. The bacterial potassium channel KcsA was the first selective ion channels to be experimentally solved (1998), and after KcsA the structures of four different potassium channels were revealed. These experimental data inspired a new era in ion channel modeling. Once the atomic structures of channels are known, it is possible to define mathematical models based on physical descriptions of the molecular systems. These physically based models can provide an atomic description of ion channel functioning, and predict the effect of structural changes. Chapter 2 introduces the computation methods used throughout the thesis to model ion channels functioning at the atomic level. In Chapter 3 and Chapter 4 the ion conduction through potassium channels is analyzed, by an approach based on the Poisson-Nernst-Planck electrodiffusion theory. In the electrodiffusion theory ion conduction is modeled by the drift-diffusion equations, thus describing the ion distributions by continuum functions. The numerical solver of the Poisson- Nernst-Planck equations was tested in the KcsA potassium channel (Chapter 3), and then used to analyze how the atomic structure of the intracellular vestibule of potassium channels affects the conductance (Chapter 4). As a major result, a correlation between the channel conductance and the potassium concentration in the intracellular vestibule emerged. The atomic structure of the channel modulates the potassium concentration in the vestibule, thus its conductance. This mechanism explains the phenotype of the BK potassium channels, a sub-family of potassium channels with high single channel conductance. The functional role of the intracellular vestibule is also the subject of Chapter 5, where the affinity of the potassium channels hEag1 (involved in tumour-cell proliferation) and hErg (important in the cardiac cycle) for several pharmaceutical drugs was compared. Both experimental measurements and molecular modeling were used in order to identify differences in the blocking mechanism of the two channels, which could be exploited in the synthesis of selective blockers. The experimental data pointed out the different role of residue mutations in the blockage of hEag1 and hErg, and the molecular modeling provided a possible explanation based on different binding sites in the intracellular vestibule. Modeling ion channels at the molecular levels relates the functioning of a channel to its atomic structure (Chapters 3-5), and can also be useful to predict the structure of ion channels (Chapter 6-7). In Chapter 6 the structure of the KcsA potassium channel depleted from potassium ions is analyzed by molecular dynamics simulations. Recently, a surprisingly high osmotic permeability of the KcsA channel was experimentally measured. All the available crystallographic structure of KcsA refers to a channel occupied by potassium ions. To conduct water molecules potassium ions must be expelled from KcsA. The structure of the potassium-depleted KcsA channel and the mechanism of water permeation are still unknown, and have been investigated by numerical simulations. Molecular dynamics of KcsA identified a possible atomic structure of the potassium-depleted KcsA channel, and a mechanism for water permeation. The depletion from potassium ions is an extreme situation for potassium channels, unlikely in physiological conditions. However, the simulation of such an extreme condition could help to identify the structural conformations, so the functional states, accessible to potassium ion channels. The last chapter of the thesis deals with the atomic structure of the !- Hemolysin channel. !-Hemolysin is the major determinant of the Staphylococcus Aureus toxicity, and is also the prototype channel for a possible usage in technological applications. The atomic structure of !- Hemolysin was revealed by X-Ray crystallography, but several experimental evidences suggest the presence of an alternative atomic structure. This alternative structure was predicted, combining experimental measurements of single channel currents and numerical simulations. This thesis is organized in two parts, in the first part an overview on ion channels and on the numerical methods adopted throughout the thesis is provided, while the second part describes the research projects tackled in the course of the PhD programme. The aim of the research activity was to relate the functional characteristics of ion channels to their atomic structure. In presenting the different research projects, the role of numerical simulations to analyze the structure-function relation in ion channels is highlighted.

Multitemporal analysis of satellite imagery: implementation of a land evolution model in ALCS (ATSR LAND CLASSIFICATION SYSTEM)

In this report it was designed an innovative satellite-based monitoring approach applied on the Iraqi Marshlands to survey the extent and distribution of marshland re-flooding and assess the development of wetland vegetation cover. The study, conducted in collaboration with MEEO Srl , makes use of images collected from the sensor (A)ATSR onboard ESA ENVISAT Satellite to collect data at multi-temporal scales and an analysis was adopted to observe the evolution of marshland re-flooding. The methodology uses a multi-temporal pixel-based approach based on classification maps produced by the classification tool SOIL MAPPER ®. The catalogue of the classification maps is available as web service through the Service Support Environment Portal (SSE, supported by ESA). The inundation of the Iraqi marshlands, which has been continuous since April 2003, is characterized by a high degree of variability, ad-hoc interventions and uncertainty. Given the security constraints and vastness of the Iraqi marshlands, as well as cost-effectiveness considerations, satellite remote sensing was the only viable tool to observe the changes taking place on a continuous basis. The proposed system (ALCS – AATSR LAND CLASSIFICATION SYSTEM) avoids the direct use of the (A)ATSR images and foresees the application of LULCC evolution models directly to „stock‟ of classified maps. This approach is made possible by the availability of a 13 year classified image database, conceived and implemented in the CARD project (http://earth.esa.int/rtd/Projects/#CARD).The approach here presented evolves toward an innovative, efficient and fast method to exploit the potentiality of multi-temporal LULCC analysis of (A)ATSR images. The two main objectives of this work are both linked to a sort of assessment: the first is to assessing the ability of modeling with the web-application ALCS using image-based AATSR classified with SOIL MAPPER ® and the second is to evaluate the magnitude, the character and the extension of wetland rehabilitation.

Slope stability analysis by multi-temporal DEMs and 3D modelling: The 2002 and 2007 Stromboli landslide events

Natural hazard related to the volcanic activity represents a potential risk factor, particularly in the vicinity of human settlements. Besides to the risk related to the explosive and effusive activity, the instability of volcanic edifices may develop into large landslides often catastrophically destructive, as shown by the collapse of the northern flank of Mount St. Helens in 1980. A combined approach was applied to analyse slope failures that occurred at Stromboli volcano. SdF slope stability was evaluated by using high-resolution multi-temporal DTMMs and performing limit equilibrium stability analyses. High-resolution topographical data collected with remote sensing techniques and three-dimensional slope stability analysis play a key role in understanding instability mechanism and the related risks. Analyses carried out on the 2002–2003 and 2007 Stromboli eruptions, starting from high-resolution data acquired through airborne remote sensing surveys, permitted the estimation of the lava volumes emplaced on the SdF slope and contributed to the investigation of the link between magma emission and slope instabilities. Limit Equilibrium analyses were performed on the 2001 and 2007 3D models, in order to simulate the slope behavior before 2002-2003 landslide event and after the 2007 eruption. Stability analyses were conducted to understand the mechanisms that controlled the slope deformations which occurred shortly after the 2007 eruption onset, involving the upper part of slope. Limit equilibrium analyses applied to both cases yielded results which are congruent with observations and monitoring data. The results presented in this work undoubtedly indicate that hazard assessment for the island of Stromboli should take into account the fact that a new magma intrusion could lead to further destabilisation of the slope, which may be more significant than the one recently observed because it will affect an already disarranged deposit and fractured and loosened crater area. The two-pronged approach based on the analysis of 3D multi-temporal mapping datasets and on the application of LE methods contributed to better understanding volcano flank behaviour and to be prepared to undertake actions aimed at risk mitigation.

Entwicklung von computergestützten Hangstabilitätsmodellen zur Erstellung einer Gefahrenhinweiskarte für die Region Rheinhessen

Das Ziel der Arbeit war die Entwicklung computergestützter Methoden zur Erstellung einer Gefahrenhinweiskarte für die Region Rheinhessen, zur Minimierung der Hangrutschungsgefährdung. Dazu wurde mit Hilfe zweier statistischer Verfahren (Diskriminanzanalyse, Lo­gistische Regression) und einer Methode aus dem Bereich der Künstlichen Intelligenz (Fuzzy Logik) versucht, die potentielle Gefährdung auch solcher Hänge zu klassifizieren, die bis heute noch nicht durch Massenbewegungen aufgefallen sind. Da ingenieurgeologische und geotechnische Hanguntersuchungen aus Zeit und Kostengründen im regionalen Maßstab nicht möglich sind, wurde auf punktuell vorhandene Datenbestände zu einzelnen Rut­schungen des Winters 1981/82, die in einer Rutschungsdatenbank zu­sammengefaßt sind, zurückgegriffen, wobei die daraus gewonnenen Erkenntnisse über Prozeßmechanismen und auslösende Faktoren genutzt und in das jeweilige Modell integriert wurden. Flächenhafte Daten (Lithologie, Hangneigung, Landnutzung, etc.), die für die Berechnung der Hangstabilität notwendig sind, wurden durch Fernerkundungsmethoden, dem Digitalisieren von Karten und der Auswertung von Digitalen Geländemodellen (Reliefanalyse) gewonnen. Für eine weiterführende Untersuchung von einzelnen, als rutschgefährdet klassifi­zierten Bereichen der Gefahrenhinweiskarte, wurde am Beispiel eines Testgebietes, eine auf dem infinite-slope-stability Modell aufbauende Me­thode untersucht, die im Maßstabsbereich von Grundkarten (1:5000) auch geotechnische und hydrogeologische Parameter berücksichtigt und damit eine genauere, der jeweiligen klimatischen Situation angepaßte, Gefahrenabschätzung ermöglicht.

Models for the Study of Cortical Activity During Cognitive ans Motor Tasks

This thesis is mainly devoted to show how EEG data and related phenomena can be reproduced and analyzed using mathematical models of neural masses (NMM). The aim is to describe some of these phenomena, to show in which ways the design of the models architecture is influenced by such phenomena, point out the difficulties of tuning the dozens of parameters of the models in order to reproduce the activity recorded with EEG systems during different kinds of experiments, and suggest some strategies to cope with these problems. In particular the chapters are organized as follows: chapter I gives a brief overview of the aims and issues addressed in the thesis; in chapter II the main characteristics of the cortical column, of the EEG signal and of the neural mass models will be presented, in order to show the relationships that hold between these entities; chapter III describes a study in which a NMM from the literature has been used to assess brain connectivity changes in tetraplegic patients; in chapter IV a modified version of the NMM is presented, which has been developed to overcomes some of the previous version’s intrinsic limitations; chapter V describes a study in which the new NMM has been used to reproduce the electrical activity evoked in the cortex by the transcranial magnetic stimulation (TMS); chapter VI presents some preliminary results obtained in the simulation of the neural rhythms associated with memory recall; finally, some general conclusions are drawn in chapter VII.

Electromagnetic simulation and measurement of diffuse scattering from building walls

Il fenomeno dello scattering diffuso è stato oggetto di numerosi studi nell’arco degli ultimi anni, questo grazie alla sua rilevanza nell’ambito della propagazione elettromagnetica così come in molti altri campi di applicazione (remote sensing, ottica, fisica, etc.), ma la compresione completa di questo effetto è lungi dall’essere raggiunta. Infatti la complessità nello studio e nella caratterizzazione della diffusione deriva dalla miriade di casistiche ed effetti che si possono incontrare in un ambiente di propagazione reale, lasciando intuire la necessità di trattarne probabilisticamente il relativo contributo. Da qui nasce l’esigenza di avere applicazioni efficienti dal punto di vista ingegneristico che coniughino la definizione rigorosa del fenomeno e la conseguente semplificazione per fini pratici. In tale visione possiamo descrivere lo scattering diffuso come la sovrapposizione di tutti quegli effetti che si scostano dalle classiche leggi dell’ottica geometrica (riflessione, rifrazione e diffrazione) che generano contributi del campo anche in punti dello spazio e direzioni in cui teoricamente, per oggetti lisci ed omogenei, non dovrebbe esserci alcun apporto. Dunque l’effetto principale, nel caso di ambiente di propagazione reale, è la diversa distribuzione spaziale del campo rispetto al caso teorico di superficie liscia ed omogenea in congiunzione ad effetti di depolarizzazione e redistribuzione di energia nel bilancio di potenza. Perciò la complessità del fenomeno è evidente e l’obiettivo di tale elaborato è di proporre nuovi risultati che permettano di meglio descrivere lo scattering diffuso ed individuare altresì le tematiche sulle quali concentrare l’attenzione nei lavori futuri. In principio è stato quindi effettuato uno studio bibliografico così da identificare i modelli e le teorie esistenti individuando i punti sui quali riflettere maggiormente; nel contempo si sono analizzate le metodologie di caratterizzazione della permittività elettrica complessa dei materiali, questo per valutare la possibilità di ricavare i parametri da utilizzare nelle simulazioni utilizzando il medesimo setup di misura ideato per lo studio della diffusione. Successivamente si è realizzato un setup di simulazione grazie ad un software di calcolo elettromagnetico (basato sul metodo delle differenze finite nel dominio del tempo) grazie al quale è stato possibile analizzare la dispersione tridimensionale dovuta alle irregolarità del materiale. Infine è stata condotta una campagna di misure in camera anecoica con un banco sperimentale realizzato ad-hoc per effettuare una caratterizzazione del fenomeno di scattering in banda larga.

Generating vegetation-spectra as a basis for global monitoring of annual vegetation cycles using DOAS satellite observations

Vegetation-cycles are of general interest for many applications. Be it for harvest-predictions, global monitoring of climate-change or as input to atmospheric models.rnrnCommon Vegetation Indices use the fact that for vegetation the difference between Red and Near Infrared reflection is higher than in any other material on Earth’s surface. This gives a very high degree of confidence for vegetation-detection.rnrnThe spectrally resolving data from the GOME and SCIAMACHY satellite-instrumentsrnprovide the chance to analyse finer spectral features throughout the Red and Near Infrared spectrum using Differential Optical Absorption Spectroscopy (DOAS). Although originally developed to retrieve information on atmospheric trace gases, we use it to gain information on vegetation. Another advantage is that this method automatically corrects for changes in the atmosphere. This renders the vegetation-information easily comparable over long time-spans.rnThe first results using previously available reference spectra were encouraging, but also indicated substantial limitations of the available reflectance spectra of vegetation. This was the motivation to create new and more suitable vegetation reference spectra within this thesis.rnThe set of reference spectra obtained is unique in its extent and also with respect to its spectral resolution and the quality of the spectral calibration. For the first time, this allowed a comprehensive investigation of the high-frequency spectral structures of vegetation reflectance and of their dependence on the viewing geometry.rnrnThe results indicate that high-frequency reflectance from vegetation is very complex and highly variable. While this is an interesting finding in itself, it also complicates the application of the obtained reference spectra to the spectral analysis of satellite observations.rnrnThe new set of vegetation reference spectra created in this thesis opens new perspectives for research. Besides refined satellite analyses, these spectra might also be used for applications on other platforms such as aircraft. First promising studies have been presented in this thesis, but the full potential for the remote sensing of vegetation from satellite (or aircraft) could bernfurther exploited in future studies.

Spatio-temporal models of the functional architecture of the visual cortex

In this work I tried to explore many aspects of cognitive visual science, each one based on different academic fields, proposing mathematical models capable to reproduce both neuro-physiological and phenomenological results that were described in the recent literature. The structure of my thesis is mainly composed of three chapters, corresponding to the three main areas of research on which I focused my work. The results of each work put the basis for the following, and their ensemble form an homogeneous and large-scale survey on the spatio-temporal properties of the architecture of the visual cortex of mammals.

Aircraft-based in-situ aerosol mass spectrometry: Chemical characterization and source identification of submicron particulate matter in the free and upper troposphere and lower stratosphere

The composition of the atmosphere is frequently perturbed by the emission of gaseous and particulate matter from natural as well as anthropogenic sources. While the impact of trace gases on the radiative forcing of the climate is relatively well understood the role of aerosol is far more uncertain. Therefore, the study of the vertical distribution of particulate matter in the atmosphere and its chemical composition contribute valuable information to bridge this gap of knowledge. The chemical composition of aerosol reveals information on properties such as radiative behavior and hygroscopicity and therefore cloud condensation or ice nucleus potential. rnThis thesis focuses on aerosol pollution plumes observed in 2008 during the POLARCAT (Polar Study using Aircraft, Remote Sensing, Surface Measurements and Models, of Climate, Chemistry, Aerosols, and Transport) campaign over Greenland in June/July and CONCERT (Contrail and Cirrus Experiment) campaign over Central and Western Europe in October/November. Measurements were performed with an Aerodyne compact time-of-flight aerosol mass spectrometer (AMS) capable of online size-resolved chemical characterization of non-refractory submicron particles. In addition, the origins of pollution plumes were determined by means of modeling tools. The characterized pollution episodes originated from a large variety of sources and were encountered at distinct altitudes. They included pure natural emissions from two volcanic eruptions in 2008. By the time of detection over Western Europe between 10 and 12 km altitude the plume was about 3 months old and composed to 71 % of particulate sulfate and 21 % of carbonaceous compounds. Also, biomass burning (BB) plumes were observed over Greenland between 4 and 7 km altitude (free troposphere) originating from Canada and East Siberia. The long-range transport took roughly one and two weeks, respectively. The aerosol was composed of 78 % organic matter and 22 % particulate sulfate. Some Canadian and all Siberian BB plumes were mixed with anthropogenic emissions from fossil fuel combustion (FF) in North America and East Asia. It was found that the contribution of particulate sulfate increased with growing influences from anthropogenic activity and Asia reaching up to 37 % after more than two weeks of transport time. The most exclusively anthropogenic emission source probed in the upper troposphere was engine exhaust from commercial aircraft liners over Germany. However, in-situ characterization of this aerosol type during aircraft chasing was not possible. All long-range transport aerosol was found to have an O:C ratio close to or greater than 1 implying that low-volatility oxygenated organic aerosol was present in each case despite the variety of origins and the large range in age from 3 to 100 days. This leads to the conclusion that organic particulate matter reaches a final and uniform state of oxygenation after at least 3 days in the free troposphere. rnExcept for aircraft exhaust all emission sources mentioned above are surface-bound and thus rely on different types of vertical transport mechanisms, such as direct high altitude injection in the case of a volcanic eruption, or severe BB, or uplift by convection, to reach higher altitudes where particles can travel long distances before removal mainly caused by cloud scavenging. A lifetime for North American mixed BB and FF aerosol of 7 to 11 days was derived. This in consequence means that emission from surface point sources, e.g. volcanoes, or regions, e.g. East Asia, do not only have a relevant impact on the immediate surroundings but rather on a hemispheric scale including such climate sensitive zones as the tropopause or the Arctic.

Mathematical Optimization Applied to Thermal and Electrical Energy Systems

This Thesis aims at building and discussing mathematical models applications focused on Energy problems, both on the thermal and electrical side. The objective is to show how mathematical programming techniques developed within Operational Research can give useful answers in the Energy Sector, how they can provide tools to support decision making processes of Companies operating in the Energy production and distribution and how they can be successfully used to make simulations and sensitivity analyses to better understand the state of the art and convenience of a particular technology by comparing it with the available alternatives. The first part discusses the fundamental mathematical background followed by a comprehensive literature review about mathematical modelling in the Energy Sector. The second part presents mathematical models for the District Heating strategic network design and incremental network design. The objective is the selection of an optimal set of new users to be connected to an existing thermal network, maximizing revenues, minimizing infrastructure and operational costs and taking into account the main technical requirements of the real world application. Results on real and randomly generated benchmark networks are discussed with particular attention to instances characterized by big networks dimensions. The third part is devoted to the development of linear programming models for optimal battery operation in off-grid solar power schemes, with consideration of battery degradation. The key contribution of this work is the inclusion of battery degradation costs in the optimisation models. As available data on relating degradation costs to the nature of charge/discharge cycles are limited, we concentrate on investigating the sensitivity of operational patterns to the degradation cost structure. The objective is to investigate the combination of battery costs and performance at which such systems become economic. We also investigate how the system design should change when battery degradation is taken into account.

Closed-loop investigation of the dynamical properties of cardiomyocyte electrophysiology by means of Dynamic clamp and Mathematical modelling

The research field of my PhD concerns mathematical modeling and numerical simulation, applied to the cardiac electrophysiology analysis at a single cell level. This is possible thanks to the development of mathematical descriptions of single cellular components, ionic channels, pumps, exchangers and subcellular compartments. Due to the difficulties of vivo experiments on human cells, most of the measurements are acquired in vitro using animal models (e.g. guinea pig, dog, rabbit). Moreover, to study the cardiac action potential and all its features, it is necessary to acquire more specific knowledge about single ionic currents that contribute to the cardiac activity. Electrophysiological models of the heart have become very accurate in recent years giving rise to extremely complicated systems of differential equations. Although describing the behavior of cardiac cells quite well, the models are computationally demanding for numerical simulations and are very difficult to analyze from a mathematical (dynamical-systems) viewpoint. Simplified mathematical models that capture the underlying dynamics to a certain extent are therefore frequently used. The results presented in this thesis have confirmed that a close integration of computational modeling and experimental recordings in real myocytes, as performed by dynamic clamp, is a useful tool in enhancing our understanding of various components of normal cardiac electrophysiology, but also arrhythmogenic mechanisms in a pathological condition, especially when fully integrated with experimental data.

Analisi di morfologie carsiche o crio-carsiche in relazione alla mobilizzazione di fluidi nella regione di Arabia Terra, Marte.

This thesis tries to interpret the origin and evolution of karst-like forms present in Arabia Terra, a region of Mars that develops in the equatorial zone of the planet. The work has been carried out specifically in the craters Crommelin (4o 91’ N-10o 51’ E), 12000088 (3o 48’ N-1o 30’ E), NE 12000088 (4° 20’ N-2° 50’ E), C "2" (3° 54’ N-1° W), and in their surrounding areas. These craters contain layered deposits characterized by a high albedo and on which erosion is very pronounced. The area containing the craters is a plateau that has the same characteristics of albedo and texture. The preliminary morphological study has made use of instrumentation such as the Mars Reconnaissance Orbiter (MRO), in particular HiRISE images (High Resolution Imaging Science Experiment), CTX (Context Camera) and CRISM (Compact Reconnaissance Imaging Spectrometers for Mars). A regional geomorphological map has been drawn up containing the main morphotypes, and detailed geomorphological maps were prepared for different karst-like morphologies. The analysis of spectral data collected from CRISM instrumentation has allowed to identify the footprint of sulphate minerals in the external area. Data were collected for morphometric negative forms (karst-like) and positive forms (mud volcanoes, dikes and pingos). For the analysis of the relief forms DTMs (Digital Terrain Models) produced by the union of stereographic CTX couples or HiRISE were used. From the analysis of high-resolution images morphological footprints similar to periglacial environments have been identified, including the presence of patterned ground and polygonal cracks found all over the area of investigation, and relief structures similar to pingos present in the crater C "2". These observations allow us to imagine a geological past with a cold climate at the equator able to freeze the few fluids present in the Martian arid terrain. The development of karst-like landforms, on the other hand, can be attributed to a subsequent improval of the weather conditions that led to a normal climate regime for the equatorial areas, resulting in the degradation of the permafrost. The melt waters have thus allowed the partial dissolution of the sulphate layers. The karst-like forms look rather fresh suggesting them to be not that old.