L'epatite E nei suidi: epidemiologia, diagnosi e filogenesi

Hepatitis E is an infectious viral disease with clinical and morphological features of acute hepatitis. The aetiological agent is the Hepatitis E virus (HEV). The disease represents an important Public Health problem in developing countries where is frequently epidemic and primarily transmitted by fecal-oral route. In the last few years, a certain number of sporadic cases have been also described in industrialized countries, Italy included. A swine HEV was first identified in 1997 and is now considered an ubiquitous virus. Human and swine strains from the same geographical region have shown to have a high level of nucleotidic omology and in experimental infections, the possibility of interspecific transmission of swine strains to humans and of human strains to non-human primates has been demonstrated. Furthermore, some seroepidemiological studies have demonstrated that people working in contact with swine have a higher risk to get infected than normal blood donors. Recently, cases of HEV hepatitis have been directly associated to the ingestion of uncooked tissues from pigs, wild boar or deer and today the disease is considered an emerging zoonosis. The aims of this thesis were: evaluate HEV prevalence in Italian swine herds (both in fattening and in breeding animals); investigate the possibility of finding HEV in livers used for human consumption; investigate if there is any correlation between HEV infection and the presence of macroscopical lesions; investigate HEV prevalence in a demographic managed wild boar population; phylogenetically analyse viral strains identified. During an internship period at Veterinary Laboratories Agency (Weybridge, UK), furthermore, swine samples at different stages of production and slurry lagoons have been analysed. Six swine herds located in North Italy have been sampled at different stage of production. The overall prevalence resulted 42%, and both breeding and fattening animals were positive for HEV infection. A longitudinal study has been conducted in a herd across all stages of production until the slaughtering age. Livers have been collected from the animals at the abattoir and 11.8% of them were positive for HEV infection. No correlations have been identified between HEV infection and macroscopical lesions in pigs affected by different pathological conditions. Of 86 wild boars tested 22 (25%) were positive for HEV. Of the swine tested in UK 21,5 % and 2 of the 9 slurry lagoons (22,2%) were positive for HEV infection. All the strains identified belonged to genotype 3 and showed high percentages of nucleotidic identity with humans and swine strains identified in Europe. The high prevalence detected in these studies confirms the widespread diffusion of HEV in swine populations in Italy and in UK. Phylogenetical analysis of identified strains, similar to those identified in autochthonous human hepatitis E cases of the same geographical area, confirm the hypothesis that pigs can be a font of zoonotical infection. The finding that a fraction of the livers inserted in the food chain are positive for HEV infection it’s of some concern for Public Health. The finding of a high HEV prevalence in all examined farms, together with the observation that infection may be sub-clinical and affect animals at slaughtering age, raise concern because of the possible risk of transmission of HEV to humans by either direct contact with infected pigs, indirect contact with environment and working instruments contaminated with pig feces, or ingestion of contaminated undercooked meat.

Models and methods for power monolithic microwave integrated circuits

Computer aided design of Monolithic Microwave Integrated Circuits (MMICs) depends critically on active device models that are accurate, computationally efficient, and easily extracted from measurements or device simulators. Empirical models of active electron devices, which are based on actual device measurements, do not provide a detailed description of the electron device physics. However they are numerically efficient and quite accurate. These characteristics make them very suitable for MMIC design in the framework of commercially available CAD tools. In the empirical model formulation it is very important to separate linear memory effects (parasitic effects) from the nonlinear effects (intrinsic effects). Thus an empirical active device model is generally described by an extrinsic linear part which accounts for the parasitic passive structures connecting the nonlinear intrinsic electron device to the external world. An important task circuit designers deal with is evaluating the ultimate potential of a device for specific applications. In fact once the technology has been selected, the designer would choose the best device for the particular application and the best device for the different blocks composing the overall MMIC. Thus in order to accurately reproducing the behaviour of different-in-size devices, good scalability properties of the model are necessarily required. Another important aspect of empirical modelling of electron devices is the mathematical (or equivalent circuit) description of the nonlinearities inherently associated with the intrinsic device. Once the model has been defined, the proper measurements for the characterization of the device are performed in order to identify the model. Hence, the correct measurement of the device nonlinear characteristics (in the device characterization phase) and their reconstruction (in the identification or even simulation phase) are two of the more important aspects of empirical modelling. This thesis presents an original contribution to nonlinear electron device empirical modelling treating the issues of model scalability and reconstruction of the device nonlinear characteristics. The scalability of an empirical model strictly depends on the scalability of the linear extrinsic parasitic network, which should possibly maintain the link between technological process parameters and the corresponding device electrical response. Since lumped parasitic networks, together with simple linear scaling rules, cannot provide accurate scalable models, either complicate technology-dependent scaling rules or computationally inefficient distributed models are available in literature. This thesis shows how the above mentioned problems can be avoided through the use of commercially available electromagnetic (EM) simulators. They enable the actual device geometry and material stratification, as well as losses in the dielectrics and electrodes, to be taken into account for any given device structure and size, providing an accurate description of the parasitic effects which occur in the device passive structure. It is shown how the electron device behaviour can be described as an equivalent two-port intrinsic nonlinear block connected to a linear distributed four-port passive parasitic network, which is identified by means of the EM simulation of the device layout, allowing for better frequency extrapolation and scalability properties than conventional empirical models. Concerning the issue of the reconstruction of the nonlinear electron device characteristics, a data approximation algorithm has been developed for the exploitation in the framework of empirical table look-up nonlinear models. Such an approach is based on the strong analogy between timedomain signal reconstruction from a set of samples and the continuous approximation of device nonlinear characteristics on the basis of a finite grid of measurements. According to this criterion, nonlinear empirical device modelling can be carried out by using, in the sampled voltage domain, typical methods of the time-domain sampling theory.

Spectrum shaping and its application: spread-spectrum clock generator and circuits for ultra wide band

Electromagnetic spectrum can be identified as a resource for the designer, as well as for the manufacturer, from two complementary points of view: first, because it is a good in great demand by many different kind of applications; second, because despite its scarce availability, it may be advantageous to use more spectrum than necessary. This is the case of Spread-Spectrum Systems, those systems in which the transmitted signal is spread over a wide frequency band, much wider, in fact, than the minimum bandwidth required to transmit the information being sent. Part I of this dissertation deals with Spread-Spectrum Clock Generators (SSCG) aiming at reducing Electro Magnetic Interference (EMI) of clock signals in integrated circuits (IC) design. In particular, the modulation of the clock and the consequent spreading of its spectrum are obtained through a random modulating signal outputted by a chaotic map, i.e. a discrete-time dynamical system showing chaotic behavior. The advantages offered by this kind of modulation are highlighted. Three different prototypes of chaos-based SSCG are presented in all their aspects: design, simulation, and post-fabrication measurements. The third one, operating at a frequency equal to 3GHz, aims at being applied to Serial ATA, standard de facto for fast data transmission to and from Hard Disk Drives. The most extreme example of spread-spectrum signalling is the emerging ultra-wideband (UWB) technology, which proposes the use of large sections of the radio spectrum at low amplitudes to transmit high-bandwidth digital data. In part II of the dissertation, two UWB applications are presented, both dealing with the advantages as well as with the challenges of a wide-band system, namely: a chaos-based sequence generation method for reducing Multiple Access Interference (MAI) in Direct Sequence UWB Wireless-Sensor-Networks (WSNs), and design and simulations of a Low-Noise Amplifier (LNA) for impulse radio UWB. This latter topic was studied during a study-abroad period in collaboration with Delft University of Technology, Delft, Netherlands.

Design methodologies of microwawe integrated circuits for satellite telecommunications

The running innovation processes of the microwave transistor technologies, used in the implementation of microwave circuits, have to be supported by the study and development of proper design methodologies which, depending on the applications, will fully exploit the technology potentialities. After the choice of the technology to be used in the particular application, the circuit designer has few degrees of freedom when carrying out his design; in the most cases, due to the technological constrains, all the foundries develop and provide customized processes optimized for a specific performance such as power, low-noise, linearity, broadband etc. For these reasons circuit design is always a “compromise”, an investigation for the best solution to reach a trade off between the desired performances. This approach becomes crucial in the design of microwave systems to be used in satellite applications; the tight space constraints impose to reach the best performances under proper electrical and thermal de-rated conditions, respect to the maximum ratings provided by the used technology, in order to ensure adequate levels of reliability. In particular this work is about one of the most critical components in the front-end of a satellite antenna, the High Power Amplifier (HPA). The HPA is the main power dissipation source and so the element which mostly engrave on space, weight and cost of telecommunication apparatus; it is clear from the above reasons that design strategies addressing optimization of power density, efficiency and reliability are of major concern. Many transactions and publications demonstrate different methods for the design of power amplifiers, highlighting the availability to obtain very good levels of output power, efficiency and gain. Starting from existing knowledge, the target of the research activities summarized in this dissertation was to develop a design methodology capable optimize power amplifier performances complying all the constraints imposed by the space applications, tacking into account the thermal behaviour in the same manner of the power and the efficiency. After a reminder of the existing theories about the power amplifier design, in the first section of this work, the effectiveness of the methodology based on the accurate control of the dynamic Load Line and her shaping will be described, explaining all steps in the design of two different kinds of high power amplifiers. Considering the trade-off between the main performances and reliability issues as the target of the design activity, we will demonstrate that the expected results could be obtained working on the characteristics of the Load Line at the intrinsic terminals of the selected active device. The methodology proposed in this first part is based on the assumption that designer has the availability of an accurate electrical model of the device; the variety of publications about this argument demonstrates that it is so difficult to carry out a CAD model capable to taking into account all the non-ideal phenomena which occur when the amplifier operates at such high frequency and power levels. For that, especially for the emerging technology of Gallium Nitride (GaN), in the second section a new approach for power amplifier design will be described, basing on the experimental characterization of the intrinsic Load Line by means of a low frequency high power measurements bench. Thanks to the possibility to develop my Ph.D. in an academic spin-off, MEC – Microwave Electronics for Communications, the results of this activity has been applied to important research programs requested by space agencies, with the aim support the technological transfer from universities to industrial world and to promote a science-based entrepreneurship. For these reasons the proposed design methodology will be explained basing on many experimental results.

Sviluppo di algoritmi avanzati di analisi e diagnosi combustione in tempo reale per motori endotermici alternativi

Increasingly stringent exhaust emission limits and higher fuel economy are the main drivers of the engine development process. As a consequence, the complexity of the propulsion units and its subsystems increase, due to the extensive use of sensors and actuators needed to obtain a precise control over the combustion phase. Since engine calibration process consumes most of the development time, new tools and methodologies are needed to shorten the development time and increase the performance attainable. Real time combustion analysis, based on the in-cylinder pressure signal, can significantly improve the calibration of the engine control strategies and the development of new algorithms, giving instantaneous feedback on the engine behavior. A complete combustion analysis and diagnosis system has been developed, capable of evaluating the most important indicators about the combustion process, such as indicated mean effective pressure, heat release, mass fraction burned and knock indexes. Such a tool is built on top of a flexible, modular and affordable hardware platform, capable of satisfying the requirements needed for accuracy and precision, but also enabling the use directly on-board the vehicle, due to its small form factor.

Il cane come modello animale spontaneo di patologie neoplastiche dell'uomo: ene Ataxia-Telangiectasia Mutated (ATM) Nnella predisposizione al cancro ed importanza dei riarrangimanti genici dei geni Ig/TCR per la diagnosi e prognosi delle malattie linfoproliferative

“Naturally occurring cancers in pet dogs and humans share many features, including histological appearance, tumour genetics, molecular targets, biological behaviour and response to conventional therapies. Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone. The value of this opportunity has been increasingly recognized in the field of cancer research for the identification of cancer-associated genes, the study of environmental risk factors, understanding tumour biology and progression, and, perhaps most importantly, the evaluation and development of novel cancer therapeutics”.(Paoloni and Khanna, 2008) In last years, the author has investigated some molecular features of cancer in dogs. The Thesis is articulated in two main sections. In section 1, the preliminary results of a research project aimed at investigating the role of somatic mutations of Ataxia-Telangiectasia mutated (ATM) gene in predisposing to cancer in boxer dogs, are presented. The canine boxer breed may be considered an unique opportunity to disclose the role of ATM somatic mutation since boxer dogs are known to be dramatically susceptible to cancer and since they may be considered a closed gene pool. Furthermore, dogs share with human the some environment. Overall, the abovementioned features could be considered extremely useful for our purposes. In the section 2, the results of our studies aimed at setting up accurate and sensitive molecular assays for diagnosing and assessing minimal residual disease in lymphoproliferative disorders of dogs, are presented. The results of those molecular assay may be directly translated in the field of Veterinary practice as well as the may be used to improve our objective evaluation of new investigational drugs effectiveness in canine cancer trials.

Accuratezza nella diagnosi prenatale di malformazione fetale

OBJECTIVE: One major problem in counselling couples with a prenatal diagnosis of a correctable fetal anomaly is the ability to exclude associated malformations that may modify the prognosis. Our aim was to assess the precision of fetal sonography in identifying isolated malformations. METHODS: We retrospectively reviewed the prenatal and postnatal records of our center for cases with a prenatal diagnosis of an isolated fetal anomaly in the period 2002-2007. RESULTS: The antenatal diagnosis of an isolated malformation was made in 284 cases. In one of this cases the anomaly disappeared in utero. Of the remaining cases, the prenatal diagnosis was confirmed after birth in 251 (88.7%). In 8 fetuses (7 with a suspected coarctation of the aorta, 1 with ventricular septal defect) the prenatal diagnosis was not confirmed. In 24 fetuses (8.5%) additional malformations were detected at postnatal or post-mortem. In 16 of these cases the anomalies were mild or would not have changed the prognosis. In 8 cases (2.8%) severe anomalies were present (1 hypoplasia of the corpus callosum with ventriculomegaly, 1 tracheal agenesis, 3 cases with multiple anomalies, 1 Opitz Syndrome, 1 with CHARGE Syndrome, 1 COFS Syndrome). Two of these infants died. CONCLUSIONS: the prenatal diagnosis of an isolated fetal anomaly is highly reliable. However, the probability that additional malformations will go undetected albeit small remains tangible. In our experience, it was 2.8%.