Development of musculoskeletal models for the design and the pre-clinical validation of hip resurfacing prosthesis

Background. The surgical treatment of dysfunctional hips is a severe condition for the patient and a costly therapy for the public health. Hip resurfacing techniques seem to hold the promise of various advantages over traditional THR, with particular attention to young and active patients. Although the lesson provided in the past by many branches of engineering is that success in designing competitive products can be achieved only by predicting the possible scenario of failure, to date the understanding of the implant quality is poorly pre-clinically addressed. Thus revision is the only delayed and reliable end point for assessment. The aim of the present work was to model the musculoskeletal system so as to develop a protocol for predicting failure of hip resurfacing prosthesis. Methods. Preliminary studies validated the technique for the generation of subject specific finite element (FE) models of long bones from Computed Thomography data. The proposed protocol consisted in the numerical analysis of the prosthesis biomechanics by deterministic and statistic studies so as to assess the risk of biomechanical failure on the different operative conditions the implant might face in a population of interest during various activities of daily living. Physiological conditions were defined including the variability of the anatomy, bone densitometry, surgery uncertainties and published boundary conditions at the hip. The protocol was tested by analysing a successful design on the market and a new prototype of a resurfacing prosthesis. Results. The intrinsic accuracy of models on bone stress predictions (RMSE < 10%) was aligned to the current state of the art in this field. The accuracy of prediction on the bone-prosthesis contact mechanics was also excellent (< 0.001 mm). The sensitivity of models prediction to uncertainties on modelling parameter was found below 8.4%. The analysis of the successful design resulted in a very good agreement with published retrospective studies. The geometry optimisation of the new prototype lead to a final design with a low risk of failure. The statistical analysis confirmed the minimal risk of the optimised design over the entire population of interest. The performances of the optimised design showed a significant improvement with respect to the first prototype (+35%). Limitations. On the authors opinion the major limitation of this study is on boundary conditions. The muscular forces and the hip joint reaction were derived from the few data available in the literature, which can be considered significant but hardly representative of the entire variability of boundary conditions the implant might face over the patients population. This moved the focus of the research on modelling the musculoskeletal system; the ongoing activity is to develop subject-specific musculoskeletal models of the lower limb from medical images. Conclusions. The developed protocol was able to accurately predict known clinical outcomes when applied to a well-established device and, to support the design optimisation phase providing important information on critical characteristics of the patients when applied to a new prosthesis. The presented approach does have a relevant generality that would allow the extension of the protocol to a large set of orthopaedic scenarios with minor changes. Hence, a failure mode analysis criterion can be considered a suitable tool in developing new orthopaedic devices.

Optical Design for Automatic Identification and Portable Systems

This thesis proposes design methods and test tools, for optical systems, which may be used in an industrial environment, where not only precision and reliability but also ease of use is important. The approach to the problem has been conceived to be as general as possible, although in the present work, the design of a portable device for automatic identification applications has been studied, because this doctorate has been funded by Datalogic Scanning Group s.r.l., a world-class producer of barcode readers. The main functional components of the complete device are: electro-optical imaging, illumination and pattern generator systems. For what concerns the electro-optical imaging system, a characterization tool and an analysis one has been developed to check if the desired performance of the system has been achieved. Moreover, two design tools for optimizing the imaging system have been implemented. The first optimizes just the core of the system, the optical part, improving its performance ignoring all other contributions and generating a good starting point for the optimization of the whole complex system. The second tool optimizes the system taking into account its behavior with a model as near as possible to reality including optics, electronics and detection. For what concerns the illumination and the pattern generator systems, two tools have been implemented. The first allows the design of free-form lenses described by an arbitrary analytical function exited by an incoherent source and is able to provide custom illumination conditions for all kind of applications. The second tool consists of a new method to design Diffractive Optical Elements excited by a coherent source for large pattern angles using the Iterative Fourier Transform Algorithm. Validation of the design tools has been obtained, whenever possible, comparing the performance of the designed systems with those of fabricated prototypes. In other cases simulations have been used.

Design, development and first evaluation of a client/server system for managing and querying linguistic corpora

This thesis is concerned with the role played by software tools in the analysis and dissemination of linguistic corpora and their contribution to a more widespread adoption of corpora in different fields. Chapter 1 contains an overview of some of the most relevant corpus analysis tools available today, presenting their most interesting features and some of their drawbacks. Chapter 2 begins with an explanation of the reasons why none of the available tools appear to satisfy the requirements of the user community and then continues with technical overview of the current status of the new system developed as part of this work. This presentation is followed by highlights of features that make the system appealing to users and corpus builders (i.e. scholars willing to make their corpora available to the public). The chapter concludes with an indication of future directions for the projects and information on the current availability of the software. Chapter 3 describes the design of an experiment devised to evaluate the usability of the new system in comparison to another corpus tool. Usage of the tool was tested in the context of a documentation task performed on a real assignment during a translation class in a master's degree course. In chapter 4 the findings of the experiment are presented on two levels of analysis: firstly a discussion on how participants interacted with and evaluated the two corpus tools in terms of interface and interaction design, usability and perceived ease of use. Then an analysis follows of how users interacted with corpora to complete the task and what kind of queries they submitted. Finally, some general conclusions are drawn and areas for future work are outlined.

Discrete Event Systems based Design Patterns for Diagnosability Analysis of Automated Manufacturing Systems

The main goal of this thesis is to facilitate the process of industrial automated systems development applying formal methods to ensure the reliability of systems. A new formulation of distributed diagnosability problem in terms of Discrete Event Systems theory and automata framework is presented, which is then used to enforce the desired property of the system, rather then just verifying it. This approach tackles the state explosion problem with modeling patterns and new algorithms, aimed for verification of diagnosability property in the context of the distributed diagnosability problem. The concepts are validated with a newly developed software tool.

Design and experimental characterization of antennas and wireless systems for innovative wearable and implantable ultra low–power applications

The present PhD thesis exploits the design skills I have been improving since my master thesis’ research. A brief description of the chapters’ content follows. Chapter 1: the simulation of a complete front–end is a very complex problem and, in particular, is the basis upon which the prediction of the overall performance of the system is possible. By means of a commercial EM simulation tool and a rigorous nonlinear/EM circuit co–simulation based on the Reciprocity Theorem, the above–mentioned prediction can be achieved and exploited for wireless links characterization. This will represent the theoretical basics of the entire present thesis and will be supported by two RF applications. Chapter 2: an extensive dissertation about Magneto–Dielectric (MD) materials will be presented, together with their peculiar characteristics as substrates for antenna miniaturization purposes. A designed and tested device for RF on–body applications will be described in detail. Finally, future research will be discussed. Chapter 3: this chapter will deal with the issue regarding the exploitation of renewable energy sources for low–energy consumption devices. Hence the problem related to the so–called energy harvesting will be tackled and a first attempt to deploy THz solar energy in an innovative way will be presented and discussed. Future research will be proposed as well. Chapter 4: graphene is a very promising material for devices to be exploited in the RF and THz frequency range for a wide range of engineering applications, including those ones marked as the main research goal of the present thesis. This chapter will present the results obtained during my research period at the National Institute for Research and Development in Microtechnologies (IMT) in Bucharest, Romania. It will concern the design and manufacturing of antennas and diodes made in graphene–based technology for detection/rectification purposes.

Development of Core Design Methods and Tools for Gen-IV Heavy Liquid Metal Cooled Reactors

Heavy Liquid Metal Cooled Reactors are among the concepts, fostered by the GIF, as potentially able to comply with stringent safety, economical, sustainability, proliferation resistance and physical protection requirements. The increasing interest around these innovative systems has highlighted the lack of tools specifically dedicated to their core design stage. The present PhD thesis summarizes the three years effort of, partially, closing the mentioned gap, by rationally defining the role of codes in core design and by creating a development methodology for core design-oriented codes (DOCs) and its subsequent application to the most needed design areas. The covered fields are, in particular, the fuel assembly thermal-hydraulics and the fuel pin thermo-mechanics. Regarding the former, following the established methodology, the sub-channel code ANTEO+ has been conceived. Initially restricted to the forced convection regime and subsequently extended to the mixed one, ANTEO+, via a thorough validation campaign, has been demonstrated a reliable tool for design applications. Concerning the fuel pin thermo-mechanics, the will to include safety-related considerations at the outset of the pin dimensioning process, has given birth to the safety-informed DOC TEMIDE. The proposed DOC development methodology has also been applied to TEMIDE; given the complex interdependence patterns among the numerous phenomena involved in an irradiated fuel pin, to optimize the code final structure, a sensitivity analysis has been performed, in the anticipated application domain. The development methodology has also been tested in the verification and validation phases; the latter, due to the low availability of experiments truly representative of TEMIDE's application domain, has only been a preliminary attempt to test TEMIDE's capabilities in fulfilling the DOC requirements upon which it has been built. In general, the capability of the proposed development methodology for DOCs in delivering tools helping the core designer in preliminary setting the system configuration has been proven.

At the intersection of Behavioural Economics, Nudging and Regulation: Rethinking the process of nudge design for regulation

Alongside the developments in behavioural economics, the concept of nudge was introduced as an intervention able to guide individual behaviour towards better choices without using coercion or incentives. While behavioural teams were created inside governmental units and regulatory authorities, nudging emerged in regulatory discourse, being increasingly regarded as a regulatory instrument that could overcome the disadvantages of other tools. This thesis analyses the viability of incorporating nudges into regulation. In particular, it investigates the implications for regulators of bringing iterative experimental testing – a widespread nudge design methodology outside regulation – into their own design practices. Nudges outside regulation are routinely designed using experiments of all kinds. This thesis intends to answer whether design premises rooted in iterative experimentation are still valid in the regulatory space, an arena that nudging entered into and that is distinct from the one where it originally emerged. The design and provision of nudges using the premises of iterative experimental testing is possible, but at a cost and burden for regulatory nudge designers. Therefore, the thesis evaluates how this burden can be reduced, in particular how nudges can be feasibly designed and provided through regulation or, put differently, how to more efficiently design and provide nudging as a regulatory tool.

Design and synthesis of (pro)electrophilic compounds for investigating the multifactorial nature of neurodegenerative diseases: focus on inflammation-driven events

Neuroinflammation constitutes a major player in the etiopathology of neurodegenerative diseases (NDDs), by orchestrating several neurotoxic pathways which in concert lead to neurodegeneration. A positive feedback loop occurs between inflammation, microglia activation and misfolding processes that, alongside excitotoxicity and oxidative events, represent crucial features of this intricate scenario. The multi-layered nature of NDDs requires a deepen investigation on how these vicious cycles work. This could further help in the search for effective treatments. Electrophiles are critically involved in the modulation of a variety of neuroprotective responses. Thus, we envisioned their peculiar ability to switch on/off biological activities as a powerful tool for investigating the neurotoxic scenario driven by inflammation in NDDs. In particular, in this thesis project, we wanted to dissect at a molecular level the functional role of (pro)electrophilic moieties of previously synthesized thioesters of variously substituted trans-cinnamic acids, to identify crucial features which could interfere with amyloid aggregation as well as modulate Nrf2 and/or NF-κB activation. To this aim, we first synthesized new compounds to identify bioactive cores which could specifically modulate the intended target. Then, we systematically modified their structure to reach additional pathogenic pathways which could in tandem contribute to the inflammatory process. In particular, following the investigation of the mechanistic underpinnings involving the catechol feature in amyloid binding through the synthesis of new dihydroxyl derivatives, we incorporated the identified antiaggregating nucleus into constrained frames which could contrast neuroinflammation also through the modulation of CB2Rs. In parallel, Nrf2 and/or NF-κB antinflammatory structural requirements were combined with the neuroprotective cores of pioglitazone, an antidiabetic drug endowed with MAO-B inhibitory properties, and memantine, which notably contrasts excitotoxicity. By acting as Swiss army knives, the new set of molecules emerge as promising tools to deepen our insights into the complex scenario regulating NDDs.

Leonardo Ricci in the United States (1952-1972). A twenty-year American transfer as a turning experience in teaching and design.

The research solved the historiographic lacuna about Leonardo Ricci’s work in the United States focusing on the span 1952-1972 as a fundamental period for the architect's research, which moved from the project for the community space to macrostructures. The considered period is comprised between Ricci’s first travel to the United States and the date of his resignation from the University of Florida, one year before his resignation from the deanship of the faculty of architecture of Florence (1973). The research retraced philologically the stages of Ricci’s activity in the U.S.A. unveiling the premises and results of his American transfer, and to what extent it marked a turning period for his work as educator and designer and for the wider historiographic contest of the Sixties. The American transfer helped him grounding his belief in avoiding a priori morphological results in favor of what he called the “form-act” design method. Ricci’s research in the U.S.A. is described in his books Anonymous (XX century) and City of the Earth (unpublished). In them and in Ricci’s projects one common thread is traceable: the application of the “form-act” as the best tool to conceive urban design, a discipline established in the United States during Ricci’s first stay at M.I.T., in which he encountered the balance point between architecture and urban planning, between the architect’s sign and his being anonymous, between the collective and the individual dimension. With the notions of “anonymous architecture” and “form-act”, Urban Design and “open work” are the key words to understand Ricci’s work in the United States and in Italy. Urban design’s main goal to design the city as a collective work of art was the solution of that dychothomous research that enlivened Ricci’s work and one possible answer to that tension useful for him to seek the truth of architecture.

Optimizing AI at the Edge: from network topology design to MCU deployment

The first topic analyzed in the thesis will be Neural Architecture Search (NAS). I will focus on two different tools that I developed, one to optimize the architecture of Temporal Convolutional Networks (TCNs), a convolutional model for time-series processing that has recently emerged, and one to optimize the data precision of tensors inside CNNs. The first NAS proposed explicitly targets the optimization of the most peculiar architectural parameters of TCNs, namely dilation, receptive field, and the number of features in each layer. Note that this is the first NAS that explicitly targets these networks. The second NAS proposed instead focuses on finding the most efficient data format for a target CNN, with the granularity of the layer filter. Note that applying these two NASes in sequence allows an "application designer" to minimize the structure of the neural network employed, minimizing the number of operations or the memory usage of the network. After that, the second topic described is the optimization of neural network deployment on edge devices. Importantly, exploiting edge platforms' scarce resources is critical for NN efficient execution on MCUs. To do so, I will introduce DORY (Deployment Oriented to memoRY) -- an automatic tool to deploy CNNs on low-cost MCUs. DORY, in different steps, can manage different levels of memory inside the MCU automatically, offload the computation workload (i.e., the different layers of a neural network) to dedicated hardware accelerators, and automatically generates ANSI C code that orchestrates off- and on-chip transfers with the computation phases. On top of this, I will introduce two optimized computation libraries that DORY can exploit to deploy TCNs and Transformers on edge efficiently. I conclude the thesis with two different applications on bio-signal analysis, i.e., heart rate tracking and sEMG-based gesture recognition.

Design of mobility infrastructures to promote sustainability and accessibility of urban areas

This doctoral dissertation represents a cluster of research activities carried out at the DICAM Department of the University of Bologna during a three-year Ph.D. course. The goal of this research is to show how the development of an interconnected infrastructure network, aimed at promoting accessibility and sustainability of places, is fundamental in a framework of deep urban regeneration. Sustainable urban mobility plays an important role in improving the quality of life of citizens. From an environmental point of view, a sustainable mobility system means reducing fuel discharges and energy waste and, in general, aims to promote low carbon emissions. At the same time, a socially and economically sustainable mobility system should be accessible to everybody and create more job opportunities through better connectivity and mobility. Environmentally friendly means of transport such as non-motorized transport, electric vehicles, and hybrid vehicles play an important role in achieving sustainability but require a planned approach at the local policy level. The aim of this study is to demonstrate that, through a targeted reconnection of road and cycle-pedestrian routes, the quality of life of an urban area subject to degradation can be significantly improved just by increasing its accessibility and sustainability. Starting from a detailed study of the European policies and from the comparison with real similar cases, the case study of the Canal Port of Rimini (Italy) has been analysed within the European project FRAMESPORT. The analysis allowed the elaboration of a multicriterial methodology to get to the definition of a project proposal and of a priority scale of interventions. The applied methodology is a valuable tool that may be used in the future in similar urban contexts. Finally, the whole project was represented by using virtual reality to visually show the difference between the before and after the regeneration intervention.

Development of numerical tools for the simulation, design and optimization of a Helicon Plasma Thruster

This work thesis focuses on the Helicon Plasma Thruster (HPT) as a candidate for generating thrust for small satellites and CubeSats. Two main topics are addressed: the development of a Global Model (GM) and a 3D self-consistent numerical tool. The GM is suitable for preliminary analysis of HPTs with noble gases such as argon, neon, krypton, and xenon, and alternative propellants such as air and iodine. A lumping methodology is developed to reduce the computational cost when modelling the excited species in the plasma chemistry. A 3D self-consistent numerical tool is also developed that can treat discharges with a generic 3D geometry and model the actual plasma-antenna coupling. The tool consists of two main modules, an EM module and a FLUID module, which run iteratively until a steady state solution is converged. A third module is available for solving the plume with a simplified semi-analytical approach, a PIC code, or directly by integration of the fluid equations. Results obtained from both the numerical tools are benchmarked against experimental measures of HPTs or Helicon reactors, obtaining very good qualitative agreement with the experimental trend for what concerns the GM, and an excellent agreement of the physical trends predicted against the measured data for the 3D numerical strategy.

Computational tool for three-point hitch geometry optimization

The weight-transfer effect, consisting of the change in dynamic load distribution between the front and the rear tractor axles, is one of the most impairing phenomena for the performance, comfort, and safety of agricultural operations. Excessive weight transfer from the front to the rear tractor axle can occur during operation or maneuvering of implements connected to the tractor through the three-point hitch (TPH). In this respect, an optimal design of the TPH can ensure better dynamic load distribution and ultimately improve operational performance, comfort, and safety. In this study, a computational design tool (The Optimizer) for the determination of a TPH geometry that minimizes the weight-transfer effect is developed. The Optimizer is based on a constrained minimization algorithm. The objective function to be minimized is related to the tractor front-to-rear axle load transfer during a simulated reference maneuver performed with a reference implement on a reference soil. Simulations are based on a 3-degrees-of-freedom (DOF) dynamic model of the tractor-TPH-implement aggregate. The inertial, elastic, and viscous parameters of the dynamic model were successfully determined through a parameter identification algorithm. The geometry determined by the Optimizer complies with the ISO-730 Standard functional requirements and other design requirements. The interaction between the soil and the implement during the simulated reference maneuver was successfully validated against experimental data. Simulation results show that the adopted reference maneuver is effective in triggering the weight-transfer effect, with the front axle load exhibiting a peak-to-peak value of 27.1 kN during the maneuver. A benchmark test was conducted starting from four geometries of a commercially available TPH. As result, all the configurations were optimized by above 10%. The Optimizer, after 36 iterations, was able to find an optimized TPH geometry which allows to reduce the weight-transfer effect by 14.9%.

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.

Physical activity as a tool to improve the quality of life for individuals with hip or knee osteoarthritis

Total hip and knee replacements (THR/TKR) are considered the gold standard surgical treatments for end-stage osteoarthritis (OA), effectively alleviating pain, enhancing joint mobility and quality of life (QoL). Maintaining an active lifestyle and regular physical activity (PA) is crucial for these patients, as it can increase bone density and stability of joint prosthesis. This thesis aims to: (1) systematically review recommendations from healthcare professionals; (2) explore interventions promoting an active lifestyle post-THR and TKR; (3) investigate the primary causes of stiffness post-TKR; (4) design an exercise protocol to enhance QoL post-THR and TKR; (5) evaluate orthopedic surgeons' attitudes toward PA for patients post-THR/TKR; and (6) assess changes in QoL after a specifically designed PA intervention. The initial review revealed consensus on permissible sports activities post-surgery, but few studies addressed interventions targeting PA behaviors. Subsequently, findings highlighted key factors contributing to post-TKR stiffness, including mispositioned components, psychological distress, and obesity. Building on these insights, a PA intervention was implemented, followed by a survey investigating orthopedic surgeons' attitudes towards PA, which demonstrated a general positive attitude. Lastly, a pilot randomized controlled trial demonstrated significant enhancements in QoL, physical function, and clinical outcomes following a three-month adapted PA intervention. Future research should focus on raising awareness among individuals and healthcare professionals, fostering engagement in PA programs, and promoting active lifestyles. PA represents a valuable strategy for mitigating the burden of chronic diseases on society.