Optic Disc Margin Anatomy in Patients with Glaucoma and Normal Controls with Spectral Domain Optical Coherence Tomography

Objective: To characterize optic nerve head (ONH) anatomy related to the clinical optic disc margin with spectral domain-optical coherence tomography (SD-OCT). Design: Cross-sectional study. Participants: Patients with open-angle glaucoma with focal, diffuse, and sclerotic optic disc damage, and age-matched normal controls. Methods: High-resolution radial SD-OCT B-scans centered on the ONH were analyzed at each clock hour. For each scan, the border tissue of Elschnig was classified for obliqueness (internally oblique, externally oblique, or nonoblique) and the presence of Bruch's membrane overhanging the border tissue. Optic disc stereophotographs were co-localized to SD-OCT data with customized software. The frequency with which the disc margin identified in stereophotographs coincided with (1) Bruch's membrane opening (BMO), defined as the innermost edge of Bruch's membrane; (2) Bruch's membrane/border tissue, defined as any aspect of either outside BMO or border tissue; or (3) border tissue, defined as any aspect of border tissue alone, in the B-scans was computed at each clock hour. Main Outcome Measures: The SD-OCT structures coinciding with the disc margin in stereophotographs. Results: There were 30 patients (10 with each type of disc damage) and 10 controls, with a median (range) age of 68.1 (42-86) years and 63.5 (42-77) years, respectively. Although 28 patients (93%) had 2 or more border tissue configurations, the most predominant one was internally oblique, primarily superiorly and nasally, frequently with Bruch's membrane overhang. Externally oblique border tissue was less frequent, observed mostly inferiorly and temporally. In controls, there was predominantly internally oblique configuration around the disc. Although the configurations were not statistically different between patients and controls, they were among the 3 glaucoma groups. At most locations, the SD-OCT structure most frequently identified as the disc margin was some aspect of Bruch's membrane and border tissue external to BMO. Bruch's membrane overhang was regionally present in the majority of patients with glaucoma and controls; however, in most cases it was not visible as the disc margin. Conclusions: The clinically perceived disc margin is most likely not the innermost edge of Bruch's membrane detected by SD-OCT. These findings have important implications for the automated detection of the disc margin and estimates of the neuroretinal rim. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:738-747 (C) 2012 by the American Academy of Ophthalmology.

Structure-function Relationships Using the Cirrus Spectral Domain Optical Coherence Tomograph and Standard Automated Perimetry

Purpose: To evaluate the relationship between glaucomatous structural damage assessed by the Cirrus Spectral Domain OCT (SDOCT) and functional loss as measured by standard automated perimetry (SAP). Methods: Four hundred twenty-two eyes (78 healthy, 210 suspects, 134 glaucomatous) of 250 patients were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study and from the African Descent and Glaucoma Evaluation Study. All eyes underwent testing with the Cirrus SDOCT and SAP within a 6-month period. The relationship between parapapillary retinal nerve fiber layer thickness (RNFL) sectors and corresponding topographic SAP locations was evaluated using locally weighted scatterplot smoothing and regression analysis. SAP sensitivity values were evaluated using both linear as well as logarithmic scales. We also tested the fit of a model (Hood) for structure-function relationship in glaucoma. Results: Structure was significantly related to function for all but the nasal thickness sector. The relationship was strongest for superotemporal RNFL thickness and inferonasal sensitivity (R(2) = 0.314, P < 0.001). The Hood model fitted the data relatively well with 88% of the eyes inside the 95% confidence interval predicted by the model. Conclusions: RNFL thinning measured by the Cirrus SDOCT was associated with correspondent visual field loss in glaucoma.

Comparison between frequency domain and time domain riser analysis

In the optimization or parametric analyses of risers, several configurations must be analyzed. It is laborious to perform time domain solutions for the dynamic analysis, since they are time-consuming tasks. So, frequency domain solutions appear to be a possible alternative, mainly in the early stages of a riser design. However, frequency domain analysis is linear and requires that nonlinear effects are treated. The aim of this paper is to present a possible way to treat some of these nonlinearities, using an iterative process together with an analytical correction, and compare the results of a frequency domain analysis with the those of a full nonlinear analysis. [DOI: 10.1115/1.4006149]

Meta-models, environment and layers: agent-oriented engineering of complex systems

Traditional software engineering approaches and metaphors fall short when applied to areas of growing relevance such as electronic commerce, enterprise resource planning, and mobile computing: such areas, in fact, generally call for open architectures that may evolve dynamically over time so as to accommodate new components and meet new requirements. This is probably one of the main reasons that the agent metaphor and the agent-oriented paradigm are gaining momentum in these areas. This thesis deals with the engineering of complex software systems in terms of the agent paradigm. This paradigm is based on the notions of agent and systems of interacting agents as fundamental abstractions for designing, developing and managing at runtime typically distributed software systems. However, today the engineer often works with technologies that do not support the abstractions used in the design of the systems. For this reason the research on methodologies becomes the basic point in the scientific activity. Currently most agent-oriented methodologies are supported by small teams of academic researchers, and as a result, most of them are in an early stage and still in the first context of mostly \academic" approaches for agent-oriented systems development. Moreover, such methodologies are not well documented and very often defined and presented only by focusing on specific aspects of the methodology. The role played by meta- models becomes fundamental for comparing and evaluating the methodologies. In fact a meta-model specifies the concepts, rules and relationships used to define methodologies. Although it is possible to describe a methodology without an explicit meta-model, formalising the underpinning ideas of the methodology in question is valuable when checking its consistency or planning extensions or modifications. A good meta-model must address all the different aspects of a methodology, i.e. the process to be followed, the work products to be generated and those responsible for making all this happen. In turn, specifying the work products that must be developed implies dening the basic modelling building blocks from which they are built. As a building block, the agent abstraction alone is not enough to fully model all the aspects related to multi-agent systems in a natural way. In particular, different perspectives exist on the role that environment plays within agent systems: however, it is clear at least that all non-agent elements of a multi-agent system are typically considered to be part of the multi-agent system environment. The key role of environment as a first-class abstraction in the engineering of multi-agent system is today generally acknowledged in the multi-agent system community, so environment should be explicitly accounted for in the engineering of multi-agent system, working as a new design dimension for agent-oriented methodologies. At least two main ingredients shape the environment: environment abstractions - entities of the environment encapsulating some functions -, and topology abstractions - entities of environment that represent the (either logical or physical) spatial structure. In addition, the engineering of non-trivial multi-agent systems requires principles and mechanisms for supporting the management of the system representation complexity. These principles lead to the adoption of a multi-layered description, which could be used by designers to provide different levels of abstraction over multi-agent systems. The research in these fields has lead to the formulation of a new version of the SODA methodology where environment abstractions and layering principles are exploited for en- gineering multi-agent systems.

Scienza, Tecnica, Politica: Il Problema del Metodo nel Pensiero di Jacopo Aconcio

The aim of this PhD thesis is to study accurately and in depth the figure and the literary production of the intellectual Jacopo Aconcio. This minor author of the 16th century has long been considered a sort of “enigmatic character”, a profile which results from the work of those who, for many centuries, have left his writing to its fate: a story of constant re-readings and equally incessant oversights. This is why it is necessary to re-read Aconcio’s production in its entirety and to devote to it a monographic study. Previous scholars’ interpretations will obviously be considered, but at the same time an effort will be made to go beyond them through the analysis of both published and manuscript sources, in the attempt to attain a deeper understanding of the figure of this man, who was a Christian, a military and hydraulic engineer and a political philosopher,. The title of the thesis was chosen to emphasise how, throughout the three years of the doctorate, my research concentrated in equal measure and with the same degree of importance on all the reflections and activities of Jacopo Aconcio. My object, in fact, was to establish how and to what extent the methodological thinking of the intellectual found application in, and at the same time guided, his theoretical and practical production. I did not mention in the title the author’s religious thinking, which has always been considered by everyone the most original and interesting element of his production, because religion, from the Reformation onwards, was primarily a political question and thus it was treated by almost all the authors involved in the Protestant movement - Aconcio in the first place. Even the remarks concerning the private, intimate sphere of faith have therefore been analysed in this light: only by acknowledging the centrality of the “problem of politics” in Aconcio’s theories, in fact, is it possible to interpret them correctly. This approach proves the truth of the theoretical premise to my research, that is to say the unity and orderliness of the author’s thought: in every field of knowledge, Aconcio applies the rules of the methodus resolutiva, as a means to achieve knowledge and elaborate models of pacific cohabitation in society. Aconcio’s continuous references to method can make his writing pedant and rather complex, but at the same time they allow for a consistent and valid analysis of different disciplines. I have not considered the fact that most of his reflections appear to our eyes as strongly conditioned by the time in which he lived as a limit. To see in him, as some have done, the forerunner of Descartes’ methodological discourse or, conversely, to judge his religious theories as not very modern, is to force the thought of an author who was first and foremost a Christian man of his own time. Aconcio repeats this himself several times in his writings: he wants to provide individuals with the necessary tools to reach a full-fledged scientific knowledge in the various fields, and also to enable them to seek truth incessantly in the religious domain, which is the duty of every human being. The will to find rules, instruments, effective solutions characterizes the whole of the author’s corpus: Aconcio feels he must look for truth in all the arts, aware as he is that anything can become science as long as it is analysed with method. Nevertheless, he remains a man of his own time, a Christian convinced of the existence of God, creator and governor of the world, to whom people must account for their own actions. To neglect this fact in order to construct a “character”, a generic forerunner, but not participant, of whatever philosophical current, is a dangerous and sidetracking operation. In this study, I have highlighted how Aconcio’s arguments only reveal their full meaning when read in the context in which they were born, without depriving them of their originality but also without charging them with meanings they do not possess. Through a historical-doctrinal approach, I have tried to analyse the complex web of theories and events which constitute the substratum of Aconcio’s reflection, in order to trace the correct relations between texts and contexts. The thesis is therefore organised in six chapters, dedicated respectively to Aconcio’s biography, to the methodological question, to the author’s engineering activity, to his historical knowledge and to his religious thinking, followed by a last section concerning his fortune throughout the centuries. The above-mentioned complexity is determined by the special historical moment in which the author lived. On the one hand, thanks to the new union between science and technique, the 16th century produces discoveries and inventions which make available a previously unthinkable number of notions and lead to a “revolution” in the way of studying and teaching the different subjects, which, by producing a new form of intellectual, involved in politics but also aware of scientific-technological issues, will contribute to the subsequent birth of modern science. On the other, the 16th century is ravaged by religious conflicts, which shatter the unity of the Christian world and generate theological-political disputes which will inform the history of European states for many decades. My aim is to show how Aconcio’s multifarious activity is the conscious fruit of this historical and religious situation, as well as the attempt of an answer to the request of a new kind of engagement on the intellectual’s behalf. Plunged in the discussions around methodus, employed in the most important European courts, involved in the abrupt acceleration of technical-scientific activities, and especially concerned by the radical religious reformation brought on by the Protestant movement, Jacopo Aconcio reflects this complex conjunction in his writings, without lacking in order and consistency, differently from what many scholars assume. The object of this work, therefore, is to highlight the unity of the author’s thought, in which science, technique, faith and politics are woven into a combination which, although it may appear illogical and confused, is actually tidy and methodical, and therefore in agreement with Aconcio’s own intentions and with the specific characters of European culture in the Renaissance. This theory is confirmed by the reading of the Ars muniendorum oppidorum, Aconcio’s only work which had been up till now unavailable. I am persuaded that only a methodical reading of Aconcio’s works, without forgetting nor glorifying any single one, respects the author’s will. From De methodo (1558) onwards, all his writings are summae, guides for the reader who wishes to approach the study of the various disciplines. Undoubtedly, Satan’s Stratagems (1565) is something more, not only because of its length, but because it deals with the author’s main interest: the celebration of doubt and debate as bases on which to build religious tolerance, which is the best method for pacific cohabitation in society. This, however, does not justify the total centrality which the Stratagems have enjoyed for centuries, at the expense of a proper understanding of the author’s will to offer examples of methodological rigour in all sciences. Maybe it is precisely because of the reforming power of Aconcio’s thought that, albeit often forgotten throughout the centuries, he has never ceased to reappear and continues to draw attention, both as a man and as an author. His ideas never stop stimulating the reader’s curiosity and this may ultimately be the best demonstration of their worth, independently from the historical moment in which they come back to the surface.

B-type cytochromes of the DOMON domain superfamily (Novel redox elements of plant plasma membrane)

The aim of the present study is understanding the properties of a new group of redox proteins having in common a DOMON-type domain with characteristics of cytochromes b. The superfamily of proteins containing a DOMON of this type includes a few protein families. With the aim of better characterizing this new protein family, the present work addresses both a CyDOM protein (a cytochrome b561) and a protein only comprised of DOMON(AIR12), both of plant origin. Apoplastic ascorbate can be regenerated from monodehydroascorbate by a trans-plasma membrane redox system which uses cytosolic ascorbate as a reductant and comprises a high potential cytochrome b. We identified the major plasma membrane (PM) ascorbate-reducible b-type cytochrome of bean (Phaseolus vulgaris) and soybean (Glycine max) hypocotyls as orthologs of Arabidopsis auxin-responsive gene air12. The protein, which is glycosylated and glycosylphosphatidylinositol-anchored to the external side of the PM in vivo, was expressed in Pichia pastoris in a recombinant form, lacking the glycosylphosphatidylinositol-modification signal, and purified from the culture medium. Recombinant AIR12 is a soluble protein predicted to fold into a β-sandwich domain and belonging to the DOMON superfamily. It is shown to be a b-type cytochrome with a symmetrical α-band at 561 nm, to be fully reduced by ascorbate and fully oxidized by monodehydroascorbate. Redox potentiometry suggests that AIR12 binds two high-potential hemes (Em,7 +135 and +236 mV). Phylogenetic analyses reveal that the auxin-responsive genes AIR12 constitute a new family of plasma membrane b-type cytochromes specific to flowering plants. Although AIR12 is one of the few redox proteins of the PM characterized to date, the role of AIR12 in trans-PM electron transfer would imply interaction with other partners which are still to be identified. Another part of the present project was aimed at understanding of a soybean protein comprised of a DOMON fused with a well-defined b561 cytochrome domain (CyDOM). Various bioinformatic approaches show this protein to be composed of an N-terminal DOMON followed by b561 domain. The latter contains five transmembrane helices featuring highly conserved histidines, which might bind haem groups. The CyDOM has been cloned and expressed in the yeast Pichia pastoris, and spectroscopic analyses have been accomplished on solubilized yeast membranes. CyDOM clearly reveal the properties of b-type cytochrome. The results highlight the fact that CyDOM is clearly able to lead an electron flux through the plasmamembrane. Voltage clamp experiments demonstrate that Xenopus laevis oocytes transformed with CyDOM of soybean exhibit negative electrical currents in presence of an external electron acceptor. Analogous investigations were carried out with SDR2, a CyDOM of Drosophila melanogaster which shows an electron transport capacity even higher than plant CyDOM. As quoted above, these data reinforce those obtained in plant CyDOM on the one hand, and on the other hand allow to attribute to SDR2-like proteins the properties assigned to CyDOM. Was expressed in Regenerated tobacco roots, transiently transformed with infected a with chimeral construct GFP: CyDOM (by A. rhizogenes infection) reveals a plasmamembrane localization of CyDOM both in epidermal cells of the elongation zone of roots and in root hairs. In conclusion. Although the data presented here await to be expanded and in part clarified, it is safe to say they open a new perspective about the role of this group of proteins. The biological relevance of the functional and physiological implications of DOMON redox domains seems noteworthy, and it can but increase with future advances in research. Beyond the very finding, however interesting in itself, of DOMON domains as extracellular cytochromes, the present study testifies to the fact that cytochrome proteins containing DOMON domains of the type of “CyDOM” can transfer electrons through membranes and may represent the most important redox component of the plasmamembrane as yet discovered.

Porous Polymeric Bioresorbable Scaffolds for Tissue Engineering

Tissue engineering is a discipline that aims at regenerating damaged biological tissues by using a cell-construct engineered in vitro made of cells grown into a porous 3D scaffold. The role of the scaffold is to guide cell growth and differentiation by acting as a bioresorbable temporary substrate that will be eventually replaced by new tissue produced by cells. As a matter or fact, the obtainment of a successful engineered tissue requires a multidisciplinary approach that must integrate the basic principles of biology, engineering and material science. The present Ph.D. thesis aimed at developing and characterizing innovative polymeric bioresorbable scaffolds made of hydrolysable polyesters. The potentialities of both commercial polyesters (i.e. poly-e-caprolactone, polylactide and some lactide copolymers) and of non-commercial polyesters (i.e. poly-w-pentadecalactone and some of its copolymers) were explored and discussed. Two techniques were employed to fabricate scaffolds: supercritical carbon dioxide (scCO2) foaming and electrospinning (ES). The former is a powerful technology that enables to produce 3D microporous foams by avoiding the use of solvents that can be toxic to mammalian cells. The scCO2 process, which is commonly applied to amorphous polymers, was successfully modified to foam a highly crystalline poly(w-pentadecalactone-co-e-caprolactone) copolymer and the effect of process parameters on scaffold morphology and thermo-mechanical properties was investigated. In the course of the present research activity, sub-micrometric fibrous non-woven meshes were produced using ES technology. Electrospun materials are considered highly promising scaffolds because they resemble the 3D organization of native extra cellular matrix. A careful control of process parameters allowed to fabricate defect-free fibres with diameters ranging from hundreds of nanometers to several microns, having either smooth or porous surface. Moreover, versatility of ES technology enabled to produce electrospun scaffolds from different polyesters as well as “composite” non-woven meshes by concomitantly electrospinning different fibres in terms of both fibre morphology and polymer material. The 3D-architecture of the electrospun scaffolds fabricated in this research was controlled in terms of mutual fibre orientation by properly modifying the instrumental apparatus. This aspect is particularly interesting since the micro/nano-architecture of the scaffold is known to affect cell behaviour. Since last generation scaffolds are expected to induce specific cell response, the present research activity also explored the possibility to produce electrospun scaffolds bioactive towards cells. Bio-functionalized substrates were obtained by loading polymer fibres with growth factors (i.e. biomolecules that elicit specific cell behaviour) and it was demonstrated that, despite the high voltages applied during electrospinning, the growth factor retains its biological activity once released from the fibres upon contact with cell culture medium. A second fuctionalization approach aiming, at a final stage, at controlling cell adhesion on electrospun scaffolds, consisted in covering fibre surface with highly hydrophilic polymer brushes of glycerol monomethacrylate synthesized by Atom Transfer Radical Polymerization. Future investigations are going to exploit the hydroxyl groups of the polymer brushes for functionalizing the fibre surface with desired biomolecules. Electrospun scaffolds were employed in cell culture experiments performed in collaboration with biochemical laboratories aimed at evaluating the biocompatibility of new electrospun polymers and at investigating the effect of fibre orientation on cell behaviour. Moreover, at a preliminary stage, electrospun scaffolds were also cultured with tumour mammalian cells for developing in vitro tumour models aimed at better understanding the role of natural ECM on tumour malignity in vivo.

Architectures and design patterns for functional design of logic control and diagnostics in industrial automation

Recently in most of the industrial automation process an ever increasing degree of automation has been observed. This increasing is motivated by the higher requirement of systems with great performance in terms of quality of products/services generated, productivity, efficiency and low costs in the design, realization and maintenance. This trend in the growth of complex automation systems is rapidly spreading over automated manufacturing systems (AMS), where the integration of the mechanical and electronic technology, typical of the Mechatronics, is merging with other technologies such as Informatics and the communication networks. An AMS is a very complex system that can be thought constituted by a set of flexible working stations, one or more transportation systems. To understand how this machine are important in our society let considerate that every day most of us use bottles of water or soda, buy product in box like food or cigarets and so on. Another important consideration from its complexity derive from the fact that the the consortium of machine producers has estimated around 350 types of manufacturing machine. A large number of manufacturing machine industry are presented in Italy and notably packaging machine industry,in particular a great concentration of this kind of industry is located in Bologna area; for this reason the Bologna area is called “packaging valley”. Usually, the various parts of the AMS interact among them in a concurrent and asynchronous way, and coordinate the parts of the machine to obtain a desiderated overall behaviour is an hard task. Often, this is the case in large scale systems, organized in a modular and distributed manner. Even if the success of a modern AMS from a functional and behavioural point of view is still to attribute to the design choices operated in the definition of the mechanical structure and electrical electronic architecture, the system that governs the control of the plant is becoming crucial, because of the large number of duties associated to it. Apart from the activity inherent to the automation of themachine cycles, the supervisory system is called to perform other main functions such as: emulating the behaviour of traditional mechanical members thus allowing a drastic constructive simplification of the machine and a crucial functional flexibility; dynamically adapting the control strategies according to the different productive needs and to the different operational scenarios; obtaining a high quality of the final product through the verification of the correctness of the processing; addressing the operator devoted to themachine to promptly and carefully take the actions devoted to establish or restore the optimal operating conditions; managing in real time information on diagnostics, as a support of the maintenance operations of the machine. The kind of facilities that designers can directly find on themarket, in terms of software component libraries provides in fact an adequate support as regard the implementation of either top-level or bottom-level functionalities, typically pertaining to the domains of user-friendly HMIs, closed-loop regulation and motion control, fieldbus-based interconnection of remote smart devices. What is still lacking is a reference framework comprising a comprehensive set of highly reusable logic control components that, focussing on the cross-cutting functionalities characterizing the automation domain, may help the designers in the process of modelling and structuring their applications according to the specific needs. Historically, the design and verification process for complex automated industrial systems is performed in empirical way, without a clear distinction between functional and technological-implementation concepts and without a systematic method to organically deal with the complete system. Traditionally, in the field of analog and digital control design and verification through formal and simulation tools have been adopted since a long time ago, at least for multivariable and/or nonlinear controllers for complex time-driven dynamics as in the fields of vehicles, aircrafts, robots, electric drives and complex power electronics equipments. Moving to the field of logic control, typical for industrial manufacturing automation, the design and verification process is approached in a completely different way, usually very “unstructured”. No clear distinction between functions and implementations, between functional architectures and technological architectures and platforms is considered. Probably this difference is due to the different “dynamical framework”of logic control with respect to analog/digital control. As a matter of facts, in logic control discrete-events dynamics replace time-driven dynamics; hence most of the formal and mathematical tools of analog/digital control cannot be directly migrated to logic control to enlighten the distinction between functions and implementations. In addition, in the common view of application technicians, logic control design is strictly connected to the adopted implementation technology (relays in the past, software nowadays), leading again to a deep confusion among functional view and technological view. In Industrial automation software engineering, concepts as modularity, encapsulation, composability and reusability are strongly emphasized and profitably realized in the so-calledobject-oriented methodologies. Industrial automation is receiving lately this approach, as testified by some IEC standards IEC 611313, IEC 61499 which have been considered in commercial products only recently. On the other hand, in the scientific and technical literature many contributions have been already proposed to establish a suitable modelling framework for industrial automation. During last years it was possible to note a considerable growth in the exploitation of innovative concepts and technologies from ICT world in industrial automation systems. For what concerns the logic control design, Model Based Design (MBD) is being imported in industrial automation from software engineering field. Another key-point in industrial automated systems is the growth of requirements in terms of availability, reliability and safety for technological systems. In other words, the control system should not only deal with the nominal behaviour, but should also deal with other important duties, such as diagnosis and faults isolations, recovery and safety management. Indeed, together with high performance, in complex systems fault occurrences increase. This is a consequence of the fact that, as it typically occurs in reliable mechatronic systems, in complex systems such as AMS, together with reliable mechanical elements, an increasing number of electronic devices are also present, that are more vulnerable by their own nature. The diagnosis problem and the faults isolation in a generic dynamical system consists in the design of an elaboration unit that, appropriately processing the inputs and outputs of the dynamical system, is also capable of detecting incipient faults on the plant devices, reconfiguring the control system so as to guarantee satisfactory performance. The designer should be able to formally verify the product, certifying that, in its final implementation, it will perform itsrequired function guarantying the desired level of reliability and safety; the next step is that of preventing faults and eventually reconfiguring the control system so that faults are tolerated. On this topic an important improvement to formal verification of logic control, fault diagnosis and fault tolerant control results derive from Discrete Event Systems theory. The aimof this work is to define a design pattern and a control architecture to help the designer of control logic in industrial automated systems. The work starts with a brief discussion on main characteristics and description of industrial automated systems on Chapter 1. In Chapter 2 a survey on the state of the software engineering paradigm applied to industrial automation is discussed. Chapter 3 presentes a architecture for industrial automated systems based on the new concept of Generalized Actuator showing its benefits, while in Chapter 4 this architecture is refined using a novel entity, the Generalized Device in order to have a better reusability and modularity of the control logic. In Chapter 5 a new approach will be present based on Discrete Event Systems for the problemof software formal verification and an active fault tolerant control architecture using online diagnostic. Finally conclusive remarks and some ideas on new directions to explore are given. In Appendix A are briefly reported some concepts and results about Discrete Event Systems which should help the reader in understanding some crucial points in chapter 5; while in Appendix B an overview on the experimental testbed of the Laboratory of Automation of University of Bologna, is reported to validated the approach presented in chapter 3, chapter 4 and chapter 5. In Appendix C some components model used in chapter 5 for formal verification are reported.

Metodi di ottimizzazione morfologica nel progetto preliminare di propulsori aeronautici avanzati

The aim of this Doctoral Thesis is to develop a genetic algorithm based optimization methods to find the best conceptual design architecture of an aero-piston-engine, for given design specifications. Nowadays, the conceptual design of turbine airplanes starts with the aircraft specifications, then the most suited turbofan or turbo propeller for the specific application is chosen. In the aeronautical piston engines field, which has been dormant for several decades, as interest shifted towards turboaircraft, new materials with increased performance and properties have opened new possibilities for development. Moreover, the engine’s modularity given by the cylinder unit, makes it possible to design a specific engine for a given application. In many real engineering problems the amount of design variables may be very high, characterized by several non-linearities needed to describe the behaviour of the phenomena. In this case the objective function has many local extremes, but the designer is usually interested in the global one. The stochastic and the evolutionary optimization techniques, such as the genetic algorithms method, may offer reliable solutions to the design problems, within acceptable computational time. The optimization algorithm developed here can be employed in the first phase of the preliminary project of an aeronautical piston engine design. It’s a mono-objective genetic algorithm, which, starting from the given design specifications, finds the engine propulsive system configuration which possesses minimum mass while satisfying the geometrical, structural and performance constraints. The algorithm reads the project specifications as input data, namely the maximum values of crankshaft and propeller shaft speed and the maximal pressure value in the combustion chamber. The design variables bounds, that describe the solution domain from the geometrical point of view, are introduced too. In the Matlab® Optimization environment the objective function to be minimized is defined as the sum of the masses of the engine propulsive components. Each individual that is generated by the genetic algorithm is the assembly of the flywheel, the vibration damper and so many pistons, connecting rods, cranks, as the number of the cylinders. The fitness is evaluated for each individual of the population, then the rules of the genetic operators are applied, such as reproduction, mutation, selection, crossover. In the reproduction step the elitist method is applied, in order to save the fittest individuals from a contingent mutation and recombination disruption, making it undamaged survive until the next generation. Finally, as the best individual is found, the optimal dimensions values of the components are saved to an Excel® file, in order to build a CAD-automatic-3D-model for each component of the propulsive system, having a direct pre-visualization of the final product, still in the engine’s preliminary project design phase. With the purpose of showing the performance of the algorithm and validating this optimization method, an actual engine is taken, as a case study: it’s the 1900 JTD Fiat Avio, 4 cylinders, 4T, Diesel. Many verifications are made on the mechanical components of the engine, in order to test their feasibility and to decide their survival through generations. A system of inequalities is used to describe the non-linear relations between the design variables, and is used for components checking for static and dynamic loads configurations. The design variables geometrical boundaries are taken from actual engines data and similar design cases. Among the many simulations run for algorithm testing, twelve of them have been chosen as representative of the distribution of the individuals. Then, as an example, for each simulation, the corresponding 3D models of the crankshaft and the connecting rod, have been automatically built. In spite of morphological differences among the component the mass is almost the same. The results show a significant mass reduction (almost 20% for the crankshaft) in comparison to the original configuration, and an acceptable robustness of the method have been shown. The algorithm here developed is shown to be a valid method for an aeronautical-piston-engine preliminary project design optimization. In particular the procedure is able to analyze quite a wide range of design solutions, rejecting the ones that cannot fulfill the feasibility design specifications. This optimization algorithm could increase the aeronautical-piston-engine development, speeding up the production rate and joining modern computation performances and technological awareness to the long lasting traditional design experiences.

Synthetical engineering of supramolecular properties of large polycyclic aromatic hydrocarbons

An important property for devices is the charge-carrier mobility values for discotic organic materials like hexa-peri-hexabenzocoronenes. A close relation exists between the degree of their columnar self-arrangement of the molecules and their mobilities. Within this first step an induction of a higher order via hydrogen-bonding was considered, which mainly pointed towards the improvement of the intracolumnar stacking of the materials. For the analytics a broad range of methods was used including differential scanning calorimetry (DSC), wide-angle X-ray diffractometry (WAXS), solid-state NMR spectroscopy and scanning tunneling microscopy (STM). Indeed, a specific influence of the hydrogen-bonds could be identified, although in several cases by the cost of a severe reduction of solubility and processability. This effect was dampened by the addition of a long alkyl chain next to the hydrogen-bond exerting functional group, which resulted in an improved columnar arrangement by retention of processability. In contrast to the before mentioned example of inducing a higher intracolumnar order by hydrogen-bonding, the focus was also be set upon larger aromatic systems. The charge-carrier mobility is also in close relation to the size of the aromatic core and larger π-areas are expected to lead to improved mobilities. For photovoltaic applications a high extinction coefficient over a broad range of the spectrum is favorable, which can also be achieved by enlarging the aromatic core component. In addition the stronger π-interactions between the aromatic core components should yield an improved columnar stability and order. However the strengthening of the π-interactions between the aromatic core components led to a reduction of the solubility and the processability due to the stronger aggregation of the molecules. This required the introduction of efficiently solubilizing features in terms of long alkyl chains in the corona of the aromatic entity, in combination of a distortion of the aromatic core moiety by bulky tert-butyl groups. By this approach not only the processing and cleaning of the materials with standard laboratory techniques became possible, but moreover the first structure-rich UV/vis and a resolved 1H-NMR spectra for an aromatic system two times larger than hexa-peri-hexabenzocoronene were recorded. The bulk properties in an extruded fiber as well as on the surface showed a columnar self-assembly including a phase in which a homeotropic alignment on a substrate was observed, which turns the material into an interesting candidate for future applications in electronic devices.

Sustainable inorganic Binders and Their Applications in Building Engineering: A Green Alternative to Ordinary Portland Cement

In the last decades, the building materials and construction industry has been contributing to a great extent to generate a high impact on our environment. As it has been considered one of the key areas in which to operate to significantly reduce our footprint on environment, there has been widespread belief that particular attention now has to be paid and specific measures have to be taken to limit the use of non-renewable resources.The aim of this thesis is therefore to study and evaluate sustainable alternatives to commonly used building materials, mainly based on ordinary Portland Cement, and find a supportable path to reduce CO2 emissions and promote the re-use of waste materials. More specifically, this research explores different solutions for replacing cementitious binders in distinct application fields, particularly where special and more restricting requirements are needed, such as restoration and conservation of architectural heritage. Emphasis was thus placed on aspects and implications more closely related to the concept of non-invasivity and environmental sustainability. A first part of the research was addressed to the study and development of sustainable inorganic matrices, based on lime putty, for the pre-impregnation and on-site binding of continuous carbon fiber fabrics for structural rehabilitation and heritage restoration. Moreover, with the aim to further limit the exploitation of non-renewable resources, the synthesis of chemically activated silico-aluminate materials, as metakaolin, ladle slag or fly ash, was thus successfully achieved. New sustainable binders were hence proposed as novel building materials, suitable to be used as primary component for construction and repair mortars, as bulk materials in high-temperature applications or as matrices for high-toughness fiber reinforced composites.

Engineering Concurrent and Event-driven Web Apps: An Agent-Oriented Approach based on the simpAL Language

Web is constantly evolving, thanks to the 2.0 transition, HTML5 new features and the coming of cloud-computing, the gap between Web and traditional desktop applications is tailing off. Web-apps are more and more widespread and bring several benefits compared to traditional ones. On the other hand reference technologies, JavaScript primarly, are not keeping pace, so a paradim shift is taking place in Web programming, and so many new languages and technologies are coming out. First objective of this thesis is to survey the reference and state-of-art technologies for client-side Web programming focusing in particular on what concerns concurrency and asynchronous programming. Taking into account the problems that affect existing technologies, we finally design simpAL-web, an innovative approach to tackle Web-apps development, based on the Agent-oriented programming abstraction and the simpAL language. == Versione in italiano: Il Web è in continua evoluzione, grazie alla transizione verso il 2.0, alle nuove funzionalità introdotte con HTML5 ed all’avvento del cloud-computing, il divario tra le applicazioni Web e quelle desktop tradizionali va assottigliandosi. Le Web-apps sono sempre più diffuse e presentano diversi vantaggi rispetto a quelle tradizionali. D’altra parte le tecnologie di riferimento, JavaScript in primis, non stanno tenendo il passo, motivo per cui la programmazione Web sta andando incontro ad un cambio di paradigma e nuovi linguaggi e tecnologie stanno spuntando sempre più numerosi. Primo obiettivo di questa tesi è di passare al vaglio le tecnologie di riferimento ed allo stato dell’arte per quel che riguarda la programmmazione Web client-side, porgendo particolare attenzione agli aspetti inerenti la concorrenza e la programmazione asincrona. Considerando i principali problemi di cui soffrono le attuali tecnologie passeremo infine alla progettazione di simpAL-web, un approccio innovativo con cui affrontare lo sviluppo di Web-apps basato sulla programmazione orientata agli Agenti e sul linguaggio simpAL.

Interpreting Judgements using Knowledge Representation Methods and Computational Models of Argument

The goal of the present research is to define a Semantic Web framework for precedent modelling, by using knowledge extracted from text, metadata, and rules, while maintaining a strong text-to-knowledge morphism between legal text and legal concepts, in order to fill the gap between legal document and its semantics. The framework is composed of four different models that make use of standard languages from the Semantic Web stack of technologies: a document metadata structure, modelling the main parts of a judgement, and creating a bridge between a text and its semantic annotations of legal concepts; a legal core ontology, modelling abstract legal concepts and institutions contained in a rule of law; a legal domain ontology, modelling the main legal concepts in a specific domain concerned by case-law; an argumentation system, modelling the structure of argumentation. The input to the framework includes metadata associated with judicial concepts, and an ontology library representing the structure of case-law. The research relies on the previous efforts of the community in the field of legal knowledge representation and rule interchange for applications in the legal domain, in order to apply the theory to a set of real legal documents, stressing the OWL axioms definitions as much as possible in order to enable them to provide a semantically powerful representation of the legal document and a solid ground for an argumentation system using a defeasible subset of predicate logics. It appears that some new features of OWL2 unlock useful reasoning features for legal knowledge, especially if combined with defeasible rules and argumentation schemes. The main task is thus to formalize legal concepts and argumentation patterns contained in a judgement, with the following requirement: to check, validate and reuse the discourse of a judge - and the argumentation he produces - as expressed by the judicial text.

Role of outgrowth endothelial cells for applications in tissue engineering

Co-culture systems, consisting of outgrowth endothelial cells (OEC) and primary osteoblasts (pOB), represent a prom¬ising instrument to mimick the natural conditions in bone repair processes and provide a new concept to develop constructs for bone replacement. Furthermore, co-culture of OEC and pOB could provide new insights into the molecular and cellular mechanisms that control essential processes during bone repair. The present study described several advantages of the co-culture of pOB and OEC for bone tissue engineering applications, including beneficial effects on the angiogenic activation of OEC, as well as on the assembly of basement membrane matrix molecules and factors involved in vessel maturation and stabilization. The ongoing angiogenic process in the co-culture system proceeded during the course of co-cultivation and correlated with the upregulation of essential angiogenic factors, such as VEGF, angiopoietins, basement membrane molecules and mural cell-specific markers. Furthermore the co-culture system appeared to maintain osteogenic differentiation capacity.rnrnAdditional treatment of co-cultures with growth factors or morphogens might accelerate and improve bone formation and furthermore could be useful for potential clinical applications. In this context, the present study highlights the central role of the morphogen, sonic hedgehog, which has been shown to affect angiogenic activation as well as osteogenic differentiation in the co-culture model of OEC and pOB. Treatment of co-cultures with sonic hedgehog resulted in an increased formation of microvessel-like structures as early as after 24 hours. This proangiogenic effect was induced by the upregulation of the proangiogenic factors, VEGF, angiopoietin1 and angiopoietin 2. In contrast to treatment with a commonly used proangiogenic agent, VEGF, Shh stimulation induced an increased expression of factors associated with vessel maturation and stabilization, mediated through the upregulation of growth factors that are strongly involved in pericyte differentiation and recruitment, including PDGF-BB and TGFbeta. In addition, Shh treatment of co-cultures also resulted in an upregulation of osteogenic differentiation markers like alkaline phosphatase, osteocalcin, osteonectin and osteopontin, as well as an increased matrix calcification. This was a result of upregulation of the osteogenic differentiation regulating factors, BMP2 and RUNX2 which could be assessed in response to Shh treatment. rn

Specific enzymatic cleavage and payload release from peptide-based hybrid nanocapsules

Within this thesis, new approaches for the concepts of peptide-polymer conjugates and peptide-based hybrid nanomaterials are investigated. In the first part, the synthesis of a triblock polymer-peptide-polymer is carried out following a typical peptide coupling reaction, both in solution and on solid-phase. The peptide sequence is chosen, so that it is cleaved by an enzyme preparation of trypsin. End-functionalized polystyrene is used as a model hydrophobic polymer and coupled to the peptide sequence. The results show successful coupling reactions in both methods, while the solid phase method produced a more defined product. Suspensions, consisting of peptide-polymer conjugates particles, are prepared in water by ultrasonication. In contact with the enzyme, the peptide constituting the conjugated particles is cleaved. This demonstrates the enzymatic cleavage in heterophase of enzymatic sequence bond to hydrophobic polymers, and is of great interest for the encapsulation and delivery of hydrophobic molecules.rnA second approach is the preparation of peptide-based hybrid nanocapsules. This is achieved by interfacial polyaddition in inverse miniemulsion with the peptide sequence functionalized with additional amino acids. A method suitable to the use of a peptide sequence for interfacial polyaddition was developed. It is shown that, the polarity of the dispersed phase influences the structures prepared, from particle-like to polymeric shell with a liquid core.rnThe peptide sequence is equipped with a FRET pair (more exactly, an internally-quenched fluorescent system) which allows the real-time monitoring of the enzymatic cleavage of the recognition site. This system shows the successful cleavage of the peptide-based nanocapsules when trypsin preparation is added to the suspensions. A water-soluble fluorescent polymer is efficiently entrapped and its possible use as marker for the capsules is highlighted. Furthermore, a small water-soluble fluorescent dye (SR-101) is successfully encapsulated and the encapsulation efficiency as a function of the functionality of the peptide and the amount of comonomer equivalent (toluene diisocyanate) is studied. The dye is encapsulated at such a high concentration, that self-quenching occurs. Thus, the release of the encapsulated dye triggered by the enzymatic cleavage of the peptide results in a fluorescence recovery of the dye. The fluorescence recovery of the FRET pair in the peptide and of the encapsulated dye correlate well.rnFinally, nanocapsules based on a hepsin-cleavable peptide sequence are prepared. Hepsin is an enzyme, which is highly upregulated in prostate cancer cells. The cleavage of the nanocapsules is investigated with healthy and “cancerous” (hepsin-expressing) cell cultures. The degradation, followed via fluorescence recovery of the FRET system, is faster for the suspensions introduced in the hepsin expressing cell cultures.rnIn summary, this work tackles the domain of responsive nanomaterials for drug delivery from a new perspective. It presents the adaptation of the miniemulsion process for hybrid peptide-based materials, and their successful use in preparing specific enzyme-responsive nanoparticles, with hydrophilic payload release properties.rn