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Electrophysiological correlates of multiple object processing
Several daily activities like walking in a crowded street depend on our ability to process multiple objects simultaneously. According to some theories this ability relies on at least two stages or mechanisms related respectively to visual attention and visual working memory (WM). The early stage of multiple object processing – individuation – is a function of attention that allows the visual system to represent multiple objects simultaneously by selecting a limited number of locations and binding them to basic visual features. A second later stage related to visual working memory encodes in greater detail the indexed objects leading to their full representation. In the present thesis I investigated the functioning of multiple object processing in a set of behavioral and electrophysiological studies focusing on the modulation of two component of the event-related potentials - N2pc and CDA – which have been associated respectively to individuation and visual working memory. In all the experiments of the present thesis I established that both N2pc and CDA were modulated by the number of relevant items during the execution of an enumeration task. I exploited this effect in each Chapter of the present thesis to investigate different aspects of multiple object processing.
In particular, in the first and second experiment (Chapter 2) I assessed the existence of a capacity limit in simultaneous processing as predicted by theories of individuation. In Chapter 3 I investigated the role of distracting information in simultaneous individuation. In Chapter 4 I focused on whether high-level features (such as semantic information) are incorporated in the representations produced at the stage of individuation. Finally in Chapter 5 I assessed the role of awareness in multiple object processing using a masking paradigm.
The results provided new information on the way early individuation and late WM stages interact for successful object perception, as well as on their functional dissociation during multiple object processing
Novel data-driven analysis methods for real-time fMRI and simultaneous EEG-fMRI neuroimaging
Real-time neuroscience can be described as the use of neuroimaging techniques to extract and evaluate brain activations during their ongoing development. The possibility to track these activations opens the doors to new research modalities as well as practical applications in both clinical and everyday life. Moreover, the combination of different neuroimaging techniques, i.e. multimodality, may reduce several limitations present in each single technique. Due to the intrinsic difficulties of real-time experiments, in order to fully exploit their potentialities, advanced signal processing algorithms are needed. In particular, since brain activations are free to evolve in
an unpredictable way, data-driven algorithms have the potentials of being more suitable than model-driven ones. In fact, for example, in neurofeedback experiments brain activation tends to change its properties due to training or task eects thus evidencing the need for adaptive algorithms.
Blind Source Separation (BSS) methods, and in particular Independent Component Analysis (ICA) algorithms, are naturally suitable to such kind of conditions. Nonetheless, their applicability in this framework needs further investigations.
The goals of the present thesis are: i) to develop a working real-time set up for performing experiments; ii) to investigate different state of the art ICA algorithms with the aim of identifying the most suitable (along with their optimal parameters), to be adopted in a real-time MRI environment; iii) to investigate novel ICA-based methods for performing real-time MRI neuroimaging; iv) to investigate novel methods to perform data fusion between EEG and fMRI data acquired simultaneously.
The core of this thesis is organized around four "experiments", each one addressing one of these specic aims. The main results can be summarized as follows.
Experiment 1: a data analysis software has been implemented along with the hardware acquisition set-up for performing real-time fMRI. The set-up has been developed with the aim of having a framework into which it would be possible to test and run the novel methods proposed to perform real-time
fMRI.
Experiment 2: to select the more suitable ICA algorithm to be implemented in the system, we investigated theoretically and compared empirically the performance of 14 different ICA algorithms systematically sampling different growing window lengths, model order as well as a priori conditions
(none, spatial or temporal). Performance is evaluated by computing the spatial and temporal correlation to a target component of brain activation as well as computation time. Four algorithms are identied as best performing without prior information (constrained ICA, fastICA, jade-opac
and evd), with their corresponding parameter choices. Both spatial and temporal priors are found to almost double the similarity to the target at not computation costs for the constrained ICA method.
Experiment 3: the results and the suggested parameters choices from experiment 2 were implemented to monitor ongoing activity in a sliding-window approach to investigate different ways in which ICA-derived a priori information could be used to monitor a target independent component: i)
back-projection of constant spatial information derived from a functional localizer, ii) dynamic use of temporal , iii) spatial, or both iv) spatial-temporal ICA constrained data. The methods were evaluated based on spatial and/or temporal correlation with the target IC component monitored, computation time and intrinsic stochastic variability of the algorithms. The results show that the back-projection method offers the highest performance both in terms of time course reconstruction and speed. This method is very fast and effective as far as the monitored IC has a strong and well defined behavior, since it relies on an accurate description of the spatial behavior.
The dynamic methods oer comparable performances at cost of higher computational time. In particular the spatio-temporal method performs comparably in terms of computational time to back-projection, offering more variable performances in terms of reconstruction of spatial maps and time courses.
Experiment 4: finally, Higher Order Partial Least Square based method combined with ICA is proposed and investigated to integrate EEG-fMRI data acquired simultaneously. This method showed to be promising, although more experiments are needed
Design, Chemical Synthesis and Biological Evaluation of Potential New Antiviral Agents
Acquired Immunodeficiency Syndrome (AIDS) is a disease caused by the Human Immunodeficiency Virus (HIV). Since its discovery in 1981, more than 25 million people died due to this disease. To date, an effective HIV-1 vaccine usable in prophylaxis or in the therapy of humans has not yet been identified. The failures and limited success of HIV vaccines have reinforced the role of chemotherapy and therefore research on the development of effective drugs. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) were the early agents introduced in the therapy and currently they are the most used, based on their concurrent high activity against the virus and low toxicity against human cells. In addition, the rapid development of virus resistance against these types of drugs, needs to find new molecules able to overcome this drawback.
My thesis work started from the design of a small library of new molecules, with hybrid structures based on a template deriving from the natural product (+)-calanolide A and the synthetic molecule α-APA, both showing a potent and selective activity against reverse transcriptase. Docking calculation has allowed to select molecules having the best values of interaction energy with the viral enzyme. Chemical synthesis was carried out together with structural characterization by extensive spectroscopic analysis including NMR technique and mass spectrometry.
In particular, the synthesis of the amide group present in the structure of some amino-pyrone compounds using the standard method, resulted in the expected N-acylation, but with a C-acyl byproduct. This result has suggested to look further into the study of N,C-acylation selectivity for the ambidentate amino-pyrone moiety, whose reactivity is poorly known. Regioselectivity was investigated under different conditions (organic bases, solvent, acylating agent), also for an enamino-ester taken as a model compound. Experimental procedures were optimized in order to synthesize selectively pure N- and C-acylated compounds.
A preliminary enzymatic assay indicated a good activity in the early prepared compounds of the series, promising for the following in vitro tests on HIV infected cells of each molecule in the whole series. In addition, these compounds were tested against other common viruses for human infective pathologies. With the aim of identifying molecules with potential therapeutic applications, the antiviral activity must be related to cytostatic effect, in order to select the ones with a favored selectivity index. Unfortunately, the molecules showed paragonable values in antiviral and cytostatic effects, the latter one not easily predictable neither by the chemical structure, nor by a computational approach.
If the drug design by molecular docking has failed in selecting a new scaffold for NNRTIs, the study has driven the interest towards new potential antitumoral molecules showing activity at sub-micromolar concentration against leukemic cell lines.
Due to the structural similarity with recently studied antibacterial natural pyrones, the synthetic molecules showing the lowest values of cytotoxicity were investigated in the inhibition of bacterial strains. Some tested compounds have shown a good activity and selectivity against Gram(+) bacteria
Analysis and Characterization of Wireless Positioning Techniques in Indoor Environment
Indoor positioning, also referred to as indoor localization, shall be defined as the process of providing accurate people or objects coordinates inside a covered structure, such as an airport, an hospital,and any other building.
The applications and services which are enabled by indoor localization are various, and their number is constantly growing. Industrial monitoring and control, home automation and safety, security, logistics, information services, ubiquitous computing, health care, and ambient assisted living (AAL) are just a few of the domains that indoor positioning technology can benefit. A significant example is offered by local information pushing. In this case, a positioning system sends information to a user based on her/his location. For instance, a processing plant may push workflow information to employees regarding operating and safety procedures relevant to their locations in the plant. The positioning system tracks each employee, and has
knowledge of the floor plan of the facility as well as the procedures.
When an employee walks inside a defined perimeter of a particular area, such as packaging department, the positioning systems displays on the user’s personal device assistant (PDA) information regarding the work expected to be done in that area This significantly increases
efficiency and safety by ensuring that employees follow carefully designed guidelines. Location-enabled applications like this are becoming commonplace and will play important roles in our everyday life.
The design of a positioning system for indoor applications is to be regarded as a challenging task. In fact, the global positioning system (GPS) is a great solution for outdoor uses, but its applicability is strongly limited indoors because the signals coming from GPS satellites cannot penetrate the structure of most buildings. For this reason, considerable research interest for alternative non-satellite-based indoor positioning solutions has arisen in the last years.
Actually, the positioning problem is strictly related with the measurement of the distance between the object to be located and a number of landmarks with known coordinates. Then, the position of the target is commonly determined by means of appropriate statistical or geometrical algorithms.
Several approaches have been proposed, and various are the fundamental technologies that have been used so far. Today, distance measurement between two objects can be easily obtained by using laser-, optical- and ultrasounds-based devices. However, evident drawbacks of these systems are their sensitivity to line-of-sight (LOS) constraint,
and the strict object-to-object bearing requirement. The latter becomes an even worse downside when the topology of the system dynamically changes due to mobility of the target.
On the other hand, wireless-based ranging solutions are more insensitive to obstacles and non-alignment condition of devices. In addition, they may take advantage of existing radio modules and infrastructures used for communications. Accordingly, the ever grow-
ing popularity of mobile and portable embedded devices provided with wireless connectivity has encouraged the study and the development of radio-frequency (RF)-based positioning techniques. The core of such systems is the measurement of distance-related parameters of
the wireless signal.
The two most common approaches for wireless ranging are based on received-signal-strength (RSS) and message time-of-flight (ToF) measurements, respectively. In particular:
• the RSS-based method relies on the relationship between the measured received signal power and the transmitter-receiver distance, assuming that the signal propagation model and the transmitted power are known;
• the ToF-based technique leans on the measured signal propagation time and the light speed, owing to the fundamental law that relates distance to time.
The work presented in this dissertation is aimed at investigating and defining novel techniques for positioning in indoor environment based on wireless distance measurements.
In particular, this study is devoted to the analysis and in depth evaluation of the use of RSS and ToF measurements for different indoor positioning applications. State of the art techniques relying on RSS- and ToF-based ranging methods have already proven to be effective for the localization of objects inside buildings. Nevertheless, several limitations exist (e.g., on the accuracy of the ranging, its impact on
localization algorithms, etc.).
The work presented in this dissertation attempts to:
1. investigate the main sources of uncertainty affecting RSS- and ToF-based indoor distance measurement;
2. analyze the impact of ranging error on the accuracy of positioning;
3. propose, on the basis of the understanding gained from 1. and 2., novel and effective systems in order to overcome the above-mentioned limitations and improve localization performance.
The novel contributions of this thesis can be summarized as follows:
• In-depth analysis of both RSS- and ToF-based distance measurement techniques, in order to assess advantages and disadvantages of each of them.
• Guidelines for using different ranging methods in different conditions and applications.
• Implementation and field testing of a novel data fusion algorithm combining both RSS and ToF techniques to improve ranging accuracy.
• Theoretical and simulation-based analysis of chirp spread spectrum (CSS) signals for low-level timestamping.
• Experimental assessment of CSS-based timestamping as key enabler for high accuracy ToF-based ranging and time synchronization
Le misure di prevenzione del terrorismo e dei traffici criminosi internazionali
Obiettivo della presente ricerca è stata la ricognizione, la sistematizzazione e la critica delle misure di prevenzione negative praeter delictum del crimine globale previste dal diritto internazionale e sovranazionale. Si è cercato di adottare un metodo rispondente al carattere, appunto, globale della materia, nonché all’esigenza di offrirne una lettura sistematica universale. In questo senso, si è fatto largo uso della comparazione giuridica, al fine di individuare principi, categorie e prassi comuni, con cui interpretare anche il diritto internazionale e sovranazionale. Il lavoro si è strutturato in quattro parti. Nella prima si è introdotto il problema della possibile confusione fra pene e misure preventive predelittuali, che, applicate senza idonee garanzie di certezza legale, si prestano a fungere da pene del mero sospetto. Nella seconda parte si è affrontata l’evoluzione della prevenzione negli ordinamenti contemporanei, con particolare riferimento all’impiego di misure negative da parte del potere politico in tempi di emergenza. Nella terza parte sono state esaminate, in un quadro d’insieme, le esperienze e le categorie maturate da vari ordinamenti nazionali in materia di prevenzione. Nell’ultima parte si è cercato di interpretare alla luce di tali strumenti i modelli di prevenzione di diritto internazionale e sovranazionale. All’esito della nostra ricerca è emerso come il ricorso a misure di prevenzione negativa praeter delictum sia prerogativa comune ad ogni ordinamento giuridico, se non altro nei casi in cui vengano meno l’efficacia deterrente della pena e l’efficacia di interventi di prevenzione positiva. In certi paesi tali misure sono uno strumento ordinario di lotta alla criminalità pur sempre riconducibili ai principi garantistici del diritto penale, in altri contesti esse vengono usate quali misure eccezionali o di guerra, in una concezione utilitaristica che, in nome della ragione politica, tende a giustificare indiscriminati sacrifici delle libertà e dei diritti individuali, come la tortura e i “targeted killings”. Nonostante alcuni significativi interventi della Corte di Giustizia dell’Unione europea, la disciplina delle misure negative adottate dagli ordinamenti internazionali e sovranazionali risulta ancora troppo legata a logiche politiche e troppo svincolata da principi e garanzie in grado di tutelare, quanto meno, un nucleo inderogabile di diritti e libertà fondamentali
Porous calcium phosphate granules for biomedical applications
The repair or replacement of damaged or diseased hard tissue is a biomedical field that has been the subject of more and more interest in many areas of research and especially in the development of new biomaterials. The rise in the average age of the world population, increasing osteoporosis treatments and the spread of cancer and genetic bone diseases, has brought about the need to find solutions for patient care. To achieve this target/objective, biomaterials must simulate the body environment as much as possible and favour tissue repair by integrating them into the host site.
Calcium phosphates are used as medical implants because they have a chemical composition similar to the mineral of human bones, i.e. apatite. For this reason they are biocompatible and they can interact in a bioactive way with bone tissue.
In the present work a specific form of bone graft, in the form of calcium phosphate granules, has been developed by using the droplet extrusion technique. The granules were characterized chemically and physically, with specific attention to in vivo and in vitro analyses. The proposed method has allowed us to obtain spherical granules in very narrow micrometric size distribution (300-1200 μm) without the use of solvents or oils thus avoiding time consuming washing processes. Granules were produced with several controlled mineralogical compositions including: pure Hydroxyapatite (HA) and β-Tricalcium Phosphate (βTCP), mixtures of HA/βTCP and Hydroxyapatite/Tetracalcium phosphate (HA/TTCP), and compositions doped with zinc (for antibacterial purposes) and strontium (for anti-osteoporosis purposes). Of several interesting features, the produced granules show high interconnected microporosity (0.1-10 μm) and surface roughness, properties necessary for osteoconductivity.
The solubility behavior of granules was studied and demonstrated that the morphology and microporosity are more important in dissolution processes than chemical or mineralogical composition. Products were tested in simulated body fluid (SBF), and among the different compositions, HA/TTCP has been found to be bioactive during in vitro studies. In fact an intense precipitation of a carbonated layer of apatite was observed, associated with the high dissolution of a TTCP phase. All pure granules were demonstrated to not be cytotoxic. Bone implantations in different animal models (rabbits and primates) showed good performance of granules in the repairing of bone. The granules stimulated the bone growth without any inflammatory reactions. In particular, HA/TTCP granules exhibited excellent biomechanical properties by increasing the stability of neo-formed bone. These preliminary investigations were sufficient to show that the developed granules can be used for bone repair or replacement. However, more studies, especially for doped products, such as in vitro cells experiments, have to be performed to assure the biocompatibility and the effective stimulation of bone growth.
This work was performed in collaboration with Eurocoating S.p.A. (Trento, Italy), a company expert in biomedical coatings for prostheses and implants, and it is a part of “CaP project” co-sponsored by Provincia Autonoma di Trento (Italy)
Requirements-based Software System Adaptation
Nowadays, there are more and more software systems operating in highly open, dynamic and unpredictable environments. Moreover, as technology advances, requirements for these systems become ever more ambitious. We have reached a point where system complexity and environmental uncertainty are major challenges for the Information Technology industry. A solution proposed to deal with this challenge is to make systems (self-)adaptive, meaning they would evaluate their own behavior and performance, in order to re-plan and reconfigure their operations when needed.
In order to develop an adaptive system, one needs to account for some kind of feedback loop. A feedback loop constitutes an architectural prosthetic to a system proper, introducing monitoring and adaptation functionalities to the overall system. Even if implicit or hidden in the system's architecture, adaptive systems must have a feedback loop among their components in order to evaluate their behavior and act accordingly. In this thesis, we take a Requirements Engineering perspective to the design of adaptive software systems and, given that feedback loops constitute an (architectural) solution for adaptation, we ask the question: what is the requirements problem this solution is intended to solve?
To answer this question, we define two new classes of requirements: Awareness Requirements prescribe the indicators of requirements convergence that the system must strive to achieve, whereas Evolution Requirements represent adaptation strategies in terms of changes in the requirements models themselves. Moreover, we propose that System Identification be conducted to elicit parameters and analyze how changes in these parameters affect the monitored indicators, representing such effect using differential relations.
These new elements represent the requirements for adaptation, making feedback loops a first-class citizen in the requirements specification. Not only they assist requirements engineers in the task of elicitation and communication of adaptation requirements, but with the proper machine-readable representations, they can serve as input to a framework that implements the generic functionalities of a feedback loop, reasoning about requirements at runtime. We have developed one such framework, called Zansin, and validated our proposals through experiments based on a well-known case study adopted from the literature
Collective Memories in Wikipedia
Collective memories are precious resources for the society, because they contribute to strengthening the emotional bonding between community members, maintaining groups cohesion, and directing future behavior. Understanding the formation of the collective memories of emotional upheavals is important to a better comprehension of people's reactions and of the consequences on their psychological health. Previous studies investigated the effects of single traumatizing events, but few of them applied a quantitative approach to analyze the different psychological processes associated to the collective memories formation of upheavals on a large scale.
This thesis explores the opportunities of applying quantitative methods to the study of collective memories in a collaborative environment such as the English Wikipedia. First, the presence of commemoration processes in Wikipedia articles and talk pages about traumatic events will be investigated through the analysis of edit activity patterns. Second, natural language processing techniques will be applied to detect differences in the collective representations of traumatic and non traumatic events, in the temporal focus of old and recent traumatic events, and in the representations of natural and human-made disasters. Third, the temporal evolution of language related to emotional, cognitive and social processes will be analyzed in the talk pages of two different emotional upheavals, the 2005 London bombings and the 2011 Egyptian revolution. The results will confirm the interpretation of Wikipedia as a global memory place, and highlight specific psychological processes related to the formation of collective memories of different types of traumatic events, opening the way to the quantitative study of collective memory formation in digital collaborative environments
Existence, Uniqueness, Optimization and Stability for low Eigenvalues of some Nonlinear Operators
The thesis surveys some recent results obtained in the field of nonlinear partial differential equations and calculus of variations about eigenvalues of nonlinear operators
Legitimate and Contested: How States Respond to International Norms
States often invoke international norms to justify their foreign policy-making. In the last twenty years, a large body of literature has shown that norms matter in international politics since they provide frameworks for legitimate international action. Nevertheless, it is often overlooked that the absence of a centralized authority capable of enforcing and providing unambiguous interpretations of norms leaves states, particularly great powers, free to decide whether to recognize or reject the legitimacy of norms. In specific instances of foreign policy-making, states take actions that cohere with norms, while at other times they contest them. Operating in a decentralized system, international norms crucially depend on state support for their legitimacy, prominence, and effectiveness. Variations in the way states respond to norms call for an investigation into the domestic conditions that lead states to recognize or reject their legitimacy. These conditions will be investigated by comparing the attitudes of the United States and the United Kingdom towards the norms of humanitarian intervention and international criminal responsibility and by studying how these norms influence their policy-making. During the 1999 NATO intervention against the Federal Republic of Yugoslavia, both countries invoked the norm of humanitarian intervention. In contrast, during the 1998 Rome Conference for the adoption of the Statute of the International Criminal Court, their behavior diverged with the UK endorsing the Court and the US rejecting it. The analysis aims to discover the domestic actors that are responsible for how international norms are interpreted at the state level and the mechanisms and transmitters through which norms come to be viewed by states as legitimate or illegitimate frameworks of behavior