Design, implementation and evaluation of a virtual laboratory for Computer Engineering Education

Broad consensus has been reached within the Education and Cognitive Psychology research communities on the need to center the learning process on experimentation and concrete application of knowledge, rather than on a bare transfer of notions. Several advantages arise from this educational approach, ranging from the reinforce of students learning, to the increased opportunity for a student to gain greater insight into the studied topics, up to the possibility for learners to acquire practical skills and long-lasting proficiency. This is especially true in Engineering education, where integrating conceptual knowledge and practical skills assumes a strategic importance. In this scenario, learners are called to play a primary role. They are actively involved in the construction of their own knowledge, instead of passively receiving it. As a result, traditional, teacher-centered learning environments should be replaced by novel learner-centered solutions. Information and Communication Technologies enable the development of innovative solutions that provide suitable answers to the need for the availability of experimentation supports in educational context. Virtual Laboratories, Adaptive Web-Based Educational Systems and Computer-Supported Collaborative Learning environments can significantly foster different learner-centered instructional strategies, offering the opportunity to enhance personalization, individualization and cooperation. More specifically, they allow students to explore different kinds of materials, to access and compare several information sources, to face real or realistic problems and to work on authentic and multi-facet case studies. In addition, they encourage cooperation among peers and provide support through coached and scaffolded activities aimed at fostering reflection and meta-cognitive reasoning. This dissertation will guide readers within this research field, presenting both the theoretical and applicative results of a research aimed at designing an open, flexible, learner-centered virtual lab for supporting students in learning Information Security.

Smart tracking of composite parts: feasibility study and effect on mechanical behaviour

This research proposes a solution for integrating RFID - Radio Frequency Identification technology within a structure based on CFRPs - Carbon Fiber Reinforced Polymers. Therefore, the main objective is to use technology to monitor and track composite components during manufacturing and service life. The study can be divided into two macro-areas. The first portion of the research evaluates the impact of the composite materials used on transmitting the electromagnetic signal to and from the tag. RFID technology communicates through radio frequencies to to track and trace items associated with the tags. In the first instance, a feasibility study was carried out to assess using commercially available tags. Then, after evaluating different solutions, it was decided to incorporate the tags into coupons during production. The second portion of the research is focused on evaluating the impact on the composite material's resistance to tag embedding. It starts with designing tensile test specimens through the FEM model with different housing configurations. Subsequently, the best configuration was tested in the facilities of the In the Faculty of Aerospace Engineering at TU Delft, particularly in the Structure & Materials Laboratory, two tests were conducted: the first one based on ASTM D3039/D3039 - 14 - Standard Test Method for Tensile Properties of Polymer Matrix Composite Materials, the second one dividing the path to failure into failure intervals in a load-unload-reload. Both tests were accompanied by instruments such as DIC, AE, C-Scan and Optical Microscopes. The expected result of the inclusion of RFID tags in composite components is that it brings added value to the parts with which it is associated without affecting too much its mechanical properties. This comes first from the automatic identification of RFID during the production cycle and its useful life. As a result, improvements were made in the design of production facilities.

Design, expression, and characterization of FimH antigen as single recombinant protein or exposed on nanoparticles

Uropathogenic Escherichia coli (UPEC) accounts for approximately 85% of all urinary tract infections (UTIs), causing a global economic burden. E. coli is one of the pathogens mentioned in the ESKAPEE list drafted by OMS, meaning that the increasing antibiotic resistance acquired by UPEC is and will be a serious health problem in the future. Amongst the immunogenic antigens exposed on the surface of UPEC, FimH represent a potential target for vaccine development, since it is involved in the early stages of infection. As already demonstrated, immunizations with FimH elicit functional antibodies that prevent UPEC infections even though the number of doses required to elicit a strong immune response is not optimal. In this work, we aimed to stabilize FimH as a soluble recombinant antigen exploiting the donor strand complementation mechanism by generating different chimeric constructs constituted by FimH and FimG donor strand. To explore the potential of self-assembling nanoparticles to display FimH through genetic fusion, different constructs have been computationally designed and produced. In this work a structure-based design, using available crystal structures of FimH and three different NPs was performed to generate different constructs with optimized properties. Despite the different conditions tested, all the constructs designed (single antigen or chimeric NPs), resulted to be un-soluble proteins in E. coli. To overcome this issue a mammalian expression system has been tested. Soluble antigen expression was achieved for all constructs tested in the culture supernatants. Three novel chimeric NPs have been characterized by transmission electron microscopy (TEM) confirming the presence of correctly assembled NPs displaying UPEC antigen. In vivo study has shown a higher immunogenicity of the E. coli antigen when displayed on NPs surface compared to the single recombinant antigen. The antibodies elicited by chimeric NPs showed a higher functionality in the inhibition of bacterial adhesion.

Design, synthesis and biological evaluation of dual inhibitors of GSK-3B and Fyn kinases for the study of inflammatory pathways in neurodegenerative diseases

Neuroinflammation represents a key hallmark of neurodegenerative diseases and is the result of a complex network of signaling cascades within microglial cells. A positive feedback loop exists between inflammation, microglia activation and protein misfolding processes, that, together with oxidative stress and excitotoxicity, lead to neuronal degeneration. Therefore, targeting this vicious cycle can be beneficial for mitigating neurodegeneration and cognitive decline in central nervous system disorders. At molecular level, GSK-3B and Fyn kinases play a crucial role in microglia activation and their deregulation has been associated to many neurodegenerative diseases. Thus, we envisioned their combined targeting as an effective approach to disrupt this toxic loop. Specifically in this project, a hit compound, based on a 7-azaindole-3-aminothiazole structure, was first identified in a virtual screening campaign, and displayed a weak dual inhibitory activity on GSK-3B and Fyn, unbalanced towards the former. Then, in a commitment to uncover the structural features required for modulating the activity on the two targets, we systematically manipulated this compound by inserting various substitution patterns in different positions. The most potent compounds obtained were advanced to deeper investigations to test their ability of tackling the inflammatory burden also in cellular systems and to unveil their binding modes within the catalytic pocket. The new class of molecules synthesized emerged as a valuable tool to deepen our understanding of the complex network governing the inflammatory events in neurodegenerative disorders.

New Synthetic Polyamines as Multi-Target-Directed Ligands for the Treatment of Alzheimer's Disease and Cancer: Design, Synthesis and Biological Evaluation

Alzheimer's disease (AD) and cancer represent two of the main causes of death worldwide. They are complex multifactorial diseases and several biochemical targets have been recognized to play a fundamental role in their development. Basing on their complex nature, a promising therapeutical approach could be represented by the so-called "Multi-Target-Directed Ligand" approach. This new strategy is based on the assumption that a single molecule could hit several targets responsible for the onset and/or progression of the pathology. In particular in AD, most currently prescribed drugs aim to increase the level of acetylcholine in the brain by inhibiting the enzyme acetylcholinesterase (AChE). However, clinical experience shows that AChE inhibition is a palliative treatment, and the simple modulation of a single target does not address AD aetiology. Research into newer and more potent anti-AD agents is thus focused on compounds whose properties go beyond AChE inhibition (such as inhibition of the enzyme β-secretase and inhibition of the aggregation of beta-amyloid). Therefore, the MTDL strategy seems a more appropriate approach for addressing the complexity of AD and may provide new drugs for tackling its multifactorial nature. In this thesis, it is described the design of new MTDLs able to tackle the multifactorial nature of AD. Such new MTDLs designed are less flexible analogues of Caproctamine, one of the first MTDL owing biological properties useful for the AD treatment. These new compounds are able to inhibit the enzymes AChE, beta-secretase and to inhibit both AChE-induced and self-induced beta-amyloid aggregation. In particular, the most potent compound of the series is able to inhibit AChE in subnanomolar range, to inhibit β-secretase in micromolar concentration and to inhibit both AChE-induced and self-induced beta-amyloid aggregation in micromolar concentration. Cancer, as AD, is a very complex pathology and many different therapeutical approaches are currently use for the treatment of such pathology. However, due to its multifactorial nature the MTDL approach could be, in principle, apply also to this pathology. Aim of this thesis has been the development of new molecules owing different structural motifs able to simultaneously interact with some of the multitude of targets responsible for the pathology. The designed compounds displayed cytotoxic activity in different cancer cell lines. In particular, the most potent compounds of the series have been further evaluated and they were able to bind DNA resulting 100-fold more potent than the reference compound Mitonafide. Furthermore, these compounds were able to trigger apoptosis through caspases activation and to inhibit PIN1 (preliminary result). This last protein is a very promising target because it is overexpressed in many human cancers, it functions as critical catalyst for multiple oncogenic pathways and in several cancer cell lines depletion of PIN1 determines arrest of mitosis followed by apoptosis induction. In conclusion, this study may represent a promising starting pint for the development of new MTDLs hopefully useful for cancer and AD treatment.

Composite materials design, manufacture and evaluation

Fibre-Reinforced-Plastics are composite materials composed by thin fibres with high mechanical properties, made to work together with a cohesive plastic matrix. The huge advantages of fibre reinforced plastics over traditional materials are their high specific mechanical properties i.e. high stiffness and strength to weight ratios. This kind of composite materials is the most disruptive innovation in the structural materials field seen in recent years and the areas of potential application are still many. However, there are few aspects which limit their growth: on the one hand the information available about their properties and long term behaviour is still scarce, especially if compared with traditional materials for which there has been developed an extended database through years of use and research. On the other hand, the technologies of production are still not as developed as the ones available to form plastics, metals and other traditional materials. A third aspect is that the new properties presented by these materials e.g. their anisotropy, difficult the design of components. This thesis will provide several case-studies with advancements regarding the three limitations mentioned. In particular, the long term mechanical properties have been studied through an experimental analysis of the impact of seawater on GFRP. Regarding production methods, the pre-impregnated cured in autoclave process was considered: a rapid tooling method to produce moulds will be presented, and a study about the production of thick components. Also, two liquid composite moulding methods will be presented, with a case-study regarding a large component with sandwich structure that was produced with the Vacuum-Assisted-Resin-Infusion method, and a case-study regarding a thick con-rod beam that was produced with the Resin-Transfer-Moulding process. The final case-study will analyse the loads acting during the use of a particular sportive component, made with FRP layers and a sandwich structure, practical design rules will be provided.

Low Correlated Sequences & Architectures and Algorithms for Analog-to-Information Converters: Theory, Design, Implementation and Applications.

Most electronic systems can be described in a very simplified way as an assemblage of analog and digital components put all together in order to perform a certain function. Nowadays, there is an increasing tendency to reduce the analog components, and to replace them by operations performed in the digital domain. This tendency has led to the emergence of new electronic systems that are more flexible, cheaper and robust. However, no matter the amount of digital process implemented, there will be always an analog part to be sorted out and thus, the step of converting digital signals into analog signals and vice versa cannot be avoided. This conversion can be more or less complex depending on the characteristics of the signals. Thus, even if it is desirable to replace functions carried out by analog components by digital processes, it is equally important to do so in a way that simplifies the conversion from digital to analog signals and vice versa. In the present thesis, we have study strategies based on increasing the amount of processing in the digital domain in such a way that the implementation of analog hardware stages can be simplified. To this aim, we have proposed the use of very low quantized signals, i.e. 1-bit, for the acquisition and for the generation of particular classes of signals.

Design, synthesis and Chemical-physical characterization of photocatalytic inorganic nanocrystals for technological applications

This work was based on the synthesis and characterization of innovative crystals for biomedical and technological applications. Different types of syntheses were developed in order to obtain crystals with high photocatalytic properties. A hydrothermal synthesis was also processed to correlate the chemical-physical characteristics with synthesis parameters obtaining synthesis of nanoparticles of titanium dioxide with different morphology, size and crystalline phase depending on the variation of the synthesis parameters. Also a synthesis in water at 80 °C temperature and low pressure was developed from which anatase containing a small percentage of brookite nanoparticles were obtained, presenting a high photocatalytic activity. These particles have been used to obtain the microcrystals formed by an inorganic core of hydroxyapatite surface covered by TiO2 nanoparticles. Micrometer material with higher photocatalytic has been produced. The same nanoparticles have been functionalized with resorcinol oxidized in order to increase the photocatalytic efficiency. Photodegradation test results have confirmed this increase. Finally, synthetic nanoparticles with a waterless synthesis using formic acid and octanol, through esterification "in situ" were synthesized. Nanoparticles superficially covered by carboxylic residues able to bind a wide range of molecules to obtain further photocatalytic properties were obtained.

Design, production and testing of innovative key components of HEV/BEV powertrains

Through modelling activity, experimental campaigns, test bench and on-field validation, a complete powertrain for a BEV has been designed, assembled and used in a motorsport competition. The activity can be split in three main subjects, representing the three key components of an BEV vehicle. First of all a model of the entire powertrain has been developed in order to understand how the various design choices will influence the race lap-time. The data obtained was then used to design, build and test a first battery pack. After bench tests and track tests, it was understood that by using all the cell charac-teristics, without breaking the rules limitations, higher energy and power densities could have been achieved. An updated battery pack was then designed, produced and raced with at Motostudent 2018 re-sulting in a third place at debut. The second topic of this PhD was the design of novel inverter topologies. Three inverters have been de-signed, two of them using Gallium Nitride devices, a promising semiconductor technology that can achieve high switching speeds while maintaining low switching losses. High switching frequency is crucial to reduce the DC-Bus capacitor and then increase the power density of 3 phase inverters. The third in-verter uses classic Silicon devices but employs a ZVS (Zero Voltage Switching) topology. Despite the in-creased complexity of both the hardware and the control software, it can offer reduced switching losses by using conventional and established silicon mosfet technology. Finally, the mechanical parts of a three phase permanent magnet motor have been designed with the aim to employ it in UniBo Motorsport’s 2020 Formula Student car.

Design, development and characterization of DHA-based emulsion for Nutrilipidomics strategies

The industrial PhD project presented here is part of the R&D strategies of the Lipinutragen company. The innovation brought by the company concerns nutrilipidomics, i.e. the correlation between the lipid composition (in fatty acids) of the cell membrane and lipid-based nutraceuticals, especially starting from the well-known dependence of the lipid composition on the intake of essential fats, omega- 6 and omega-3 polyunsaturated fatty acids. Among the results obtained from the membrane lipidomic profiles, the case of autistic subjects is here highlighted, showing the significant deficiency of docosahexaenoic acid (DHA). The activity during the PhD was devoted to the nutrilipidomic approach. Part of the activities were devoted to scientific research in lipidomics: a) the study of lipidomic profiles in the frame of two collaboration projects: one with the group of Dr. I. Tueros at AZTI, Bilbao, regading obese population, and the other one regarding seed germination with the changes of the fatty acid profiles with the group of prof. A. Balestrazzi of the University of Parma; b) the liposome preparation for protection and lifetime prolongation of the peptide somatostatin, which was an important premise to the formulation of the DHA-containing microemulsion. The activities was also focused on the development of DHA-containing nutraceutical formulations in the form of emulsion, overcoming the difficulty of the capsule ingestion, to be administered orally. The work pointed to study the combination of active ingredients, based on the previous know-how regarding the bioavailability for the cell membrane incorporation. The ingredients of the formulation were studied and tested in vitro for the bioavailability of DHA to be incorporated in the cell membranes of different types of cultured cells. Part of this study is covered by non-disclosure agreement since it belongs to the know-how of Lipinutragen.

Design, synthesis and photovoltaic properties of some thiophene-based conjugated polymers for organic solar cells

The current issue of the resource of energy combined with the tendency to give a green footprint to our lifestyle have prompted the research to focus the attention on alternative sources with great strides in the optimization of polymeric photovoltaic devices. The research work described in this dissertation consists in the study of different semiconducting π-conjugated materials based on polythiophenes (Chapter I). In detail, the GRIM polymerization was deepened defining the synthetic conditions to obtain regioregular poly(3-alkylthiophene) (Chapter II). Since the use of symmetrical monomers functionalized with oxygen atom(s) allows to adopt easy synthesis leading to performing materials, disubstituted poly(3,4-dialkoxythiophene)s were successfully prepared, characterized and tested as photoactive materials in solar cells (Chapter III). A “green” resource of energy should be employed through sustainable devices and, for this purpose, the research work was continued on the synthesis of thiophene derivatives soluble in eco-friendly solvents. To make this possible, the photoactive layer was completely tailored starting from the electron-acceptor material. A fullerene derivative soluble in alcohols was successfully synthetized and adopted for the realization of the new devices (Chapter IV). New water/alcohol soluble electron-donor materials with different functional groups were prepared and their properties were compared (Chapter V). Once found the best ionic functional group, a new double-cable material was synthetized optimizing the surface area between the different materials (Chapter VI). Finally, other water/alcohol soluble materials were synthetized, characterized and used as cathode interlayers in eco-friendly devices (Chapter VII). In this work, all prepared materials were characterized by spectroscopy analyses, gel permeation chromatography and thermal analyses. Cyclic voltammetry, X-ray diffraction, atomic force microscopy and external quantum efficiency were used to investigate some peculiar aspects.