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Sviluppo di dispositivi di presa basati su forze elettroadesive
In a context of technological innovation, the aim of this thesis is to develop a technology that has gained interest in both scientific and industrial realms. This technology serves as a viable alternative to outdated and energy-consuming industrial systems. Electro-adhesive devices (EADs) leverage electrostatic forces for grasping objects or adhering to surfaces. The advantage of employing electrostatics lies in its adaptability to various materials without compromising the structure or chemistry of the object or surface. These benefits have led the industry to explore this technology as a replacement for costly vacuum systems and suction cups currently used for handling most products. Furthermore, the broad applicability of this technology extends to extreme environments, such as space with ultra-high vacuum conditions. Unfortunately, research in this area has yet to yield practical results for industrially effective gripper prototyping. This is primarily due to the inherent complexity of electro-adhesive technology, which operates on basic capacitive principles that does not find satisfying physical descriptions. This thesis aims to address these challenges through a series of studies, starting with the manufacturing process and testing of an EAD that has become the standard in our laboratory. It then delves into material and electrode geometry studies to enhance system performance, ultimately presenting potential industrial applications of the technology. All the presented results are encouraging, as they have yielded shear force values three times higher than those previously reported in the literature. The various applications have demonstrated the significant effectiveness of EADs as brakes or, more broadly, in exerting shear forces. This opens up the possibility of utilizing cutting-edge technologies to push the boundaries of technology to the fullest.Questa tesi si pone in un contesto di innovazione tecnologica con l'obiettivo di sviluppare una tecnologia che abbia un marcato interesse sia nel mondo scientifico che in quello industriale. La tecnologia descritta, chiamata elettroadesione, è un’alternativa valida a sistemi industriali obsoleti che implicano un alto consumo di energia. Si chiamano dispositivi elettroadesivi (EADs) dei sistemi capacitivi che sfruttano forze elettrostatiche per afferrare oggetti o aderire a superfici, permettendo di agire su diversi tipi di materiale evitando di compromettere la struttura e la chimica dell'oggetto o della sua superficie. Questi dispositivi hanno conquistato sempre più interesse in ambito industriale come sostituti di costosi sistemi a vuoto per alimentare ventose, attualmente utilizzate nella manipolazione della maggior parte dei prodotti. Inoltre, l’applicabilità di questa tecnologia si estende anche ad ambienti estremi, come lo spazio in cui si opera in condizioni di vuoto spinto. Purtroppo, la ricerca in questo settore non ha ancora prodotto risultati rilevanti nella prototipazione efficace di gripper industriali. Ciò è principalmente dovuto alla complessità intrinseca della fisica alla base della tecnologia, che non trova descrizioni adeguate a rappresentare fedelmente le rilevazioni empiriche. Questa tesi mira ad affrontare queste problematiche attraverso una serie di studi, a partire dal processo di produzione e test di un EAD diventato lo standard nel nostro laboratorio. Successivamente, approfondisce gli studi sui materiali e sulla geometria degli elementi che compongono l’EAD, per migliorare le prestazioni del sistema, presentando infine possibili applicazioni industriali. Le varie applicazioni presentate hanno dimostrato l'efficacia significativa degli EAD come freni o, più in generale, nell'esercitare forze di taglio, presentando forze tre volte superiori ai valori di letteratura. Ciò apre la possibilità di spingere al massimo i confini della tecnologia con l’utilizzo di all'avanguardia
Molecular engineering of the m13 phage for targeted photodynamic cancer treatment
This thesis explores the advancement of cancer treatment through targeted photodynamic therapy (PDT) using bioengineered phages. It aims to harness the specificity of phages for targeting cancer-related receptors such as EGFR and HER2, which are pivotal in numerous malignancies and associated with poor outcomes. The study commenced with the M13EGFR phage, modified to target EGFR through pIII-displayed EGFR-binding peptides, demonstrating enhanced killing efficiency when conjugated with the Rose Bengal photosensitizer. This phase underscored phages' potential in targeted PDT. A breakthrough was achieved with the development of the M137D12 phage, engineered to display the 7D12 nanobody for precise EGFR targeting, marking a shift from peptide-based to nanobody-based targeting and yielding better specificity and therapeutic results. The translational potential was highlighted through in vitro and in vivo assays employing therapeutic lasers, showing effective, specific cancer cell killing through a necrotic mechanism. Additionally, the research delved into the interaction between the M13CC phage and colon cancer models, demonstrating its ability to penetrate and disrupt cancer spheroids only upon irradiation, indicating a significant advancement in targeting cells within challenging tumor microenvironments. In summary, the thesis provides a thorough examination of the phage platform's efficacy and versatility for targeted PDT. The promising outcomes, especially with the M137D12 phage, and initial findings on a HER2-targeting phage (M13HER2), forecast a promising future for phage-mediated, targeted anticancer strategies employing photosensitizers in PDT
Two stroke cycle, novel combustion concepts and electrification for a new generation of internal combustion engines
The pursuit of decarbonization and increased efficiency in internal combustion engines (ICE) is crucial for reducing pollution in the mobility sector. While electrification is a long-term goal, ICE still has a role to play if coupled with innovative technologies. This research project explores various solutions to enhance ICE efficiency and reduce emissions, including Low Temperature Combustion (LTC), Dual fuel combustion with diesel and natural gas, and hydrogen integration.
LTC methods like Dual fuel and Reactivity Controlled Compression Ignition (RCCI) show promise in lowering emissions such as NOx, soot, and CO2. Dual fuel Diesel-Natural Gas with hydrogen addition demonstrates improved efficiency, especially at low loads. RCCI Diesel-Gasoline engines offer increased Brake Thermal Efficiency (BTE) compared to standard diesel engines while reducing specific NOx emissions.
The study compares 2-Stroke and 4-Stroke engine layouts, optimizing scavenging systems for both aircraft and vehicle applications. CFD analysis enhances specific power output while addressing injection challenges to prevent exhaust short circuits. Additionally, piston bowl shape optimization in Diesel engines running on Dual fuel (Diesel-Biogas) aims to reduce NOx emissions and enhance thermal efficiency.
Unconventional 2-Stroke architectures, such as reverse loop scavenged with valves for high-performance cars, opposed piston engines for electricity generation, and small loop scavenged engines for scooters, are also explored. These innovations, alongside ultra-lean hydrogen combustion, offer diverse pathways toward achieving climate neutrality in the transport sector
Grant-free protocols for massive multiple access
In next generation Internet-of-Things, the overhead introduced by grant-based multiple access protocols may engulf the access network as a consequence of the proliferation of connected devices. Grant-free access protocols are therefore gaining an increasing interest to support massive multiple access. In addition to scalability requirements, new demands have emerged for massive multiple access, including latency and reliability. The challenges envisaged for future wireless communication networks, particularly in the context of massive access, include: i) a very large population size of low power devices transmitting short packets; ii) an ever-increasing scalability requirement; iii) a mild fixed maximum latency requirement; iv) a non-trivial requirement on reliability. To this aim, we suggest the joint utilization of grant-free access protocols, massive MIMO at the base station side, framed schemes to let the contention start and end within a frame, and succesive interference cancellation techniques at the base station side. In essence, this approach is encapsulated in the concept of coded random access with massive MIMO processing.
These schemes can be explored from various angles, spanning the protocol stack from the physical (PHY) to the medium access control (MAC) layer. In this thesis, we delve into both of these layers, examining topics ranging from symbol-level signal processing to succesive interference cancellation-based scheduling strategies. In parallel with proposing new schemes, our work includes a theoretical analysis aimed at providing valuable system design guidelines. As a main
theoretical outcome, we propose a novel joint PHY and MAC layer design based on density evolution on sparse graphs
Inside standard and hyperspectral low-dose CT variational imaging: parameter identification and material decomposition
The main contribution of this thesis is the proposal of novel strategies for the selection of parameters arising in variational models employed for the solution of inverse problems with data corrupted by Poisson noise. In light
of the importance of using a significantly small dose of X-rays in Computed Tomography (CT), and its need of using advanced techniques to reconstruct the objects due to the high level of noise in the data, we will focus on parameter
selection principles especially for low photon-counts, i.e. low dose Computed Tomography. For completeness, since such strategies can be adopted for various scenarios where the noise in the data typically follows a Poisson distribution, we will show their performance for other applications such as photography, astronomical and microscopy imaging.
More specifically, in the first part of the thesis we will focus on low dose CT data corrupted only by Poisson noise by extending automatic selection strategies designed for Gaussian noise and improving the few existing ones for Poisson. The new approaches will show to outperform the state-of-the-art competitors especially in the low-counting regime. Moreover, we will propose to extend the best performing strategy to the hard task of multi-parameter
selection showing promising results.
Finally, in the last part of the thesis, we will introduce the problem of material decomposition for hyperspectral CT, which data encodes information of how different materials in the target attenuate X-rays in different ways according to the specific energy. We will conduct a preliminary comparative study to obtain accurate material decomposition starting from few noisy projection data
The RAS-Lung project: implementing blood and tissue genotyping in KRAS-Positive non-small cell lung cancer treatment
Background: The frontline management of non-oncogene addicted non-small cell lung cancer (NSCLC) involves immunotherapy (ICI) alone or combined with chemotherapy (CT-ICI). As therapeutic options expand, refining NSCLC genotyping gains paramount importance. The dynamic landscape of KRAS-positive NSCLC presents a spectrum of treatment options, including ICI, targeted therapy, and combination strategies currently under investigation.
Methods: The two-year RASLUNG project, featuring both retrospective and prospective cohorts, aimed to analyze the predictive and prognostic impact of KRAS mutations on tumor tissue and circulating DNA (ctDNA). Secondary objectives included assessing the roles of co-mutations and longitudinal changes in KRAS mutant copies concerning treatment response and survival outcomes. An external validation study confirmed the prognostic or predictive significance of co-mutations.
Results: In the prospective cohort (n=24), patients with liver metastases exhibited significantly elevated ctDNA levels(p=0.01), while those with >3 metastatic sites showed increased Allele Frequency (AF) (P=0.002). Median overall survival (OS) was 7.5 months, progression-free survival (PFS) was 4.0 months, and the objective response rate (ORR) was 33.3%. Higher AF correlated with an increased risk of death (HR 1.04, p = 0.03), though not progression. Notably, a reduction in plasma DNA levels was significantly associated with objective response(p=0.01). In the retrospective cohort, KRAS and STK11 mutations co-occurred in 14/21 patients (p=0.053). STK11 mutations were independently detrimental to OS (HR 1.97, p=0.025) after adjusting for various factors. KRAS tissue AF did not correlate with OS or PFS. Within the validation dataset, STK11 mutations were significantly associated with an increased risk of death in univariate (HR 2.01, p<0.001) and multivariate models (HR 1.66, p=0.001) after adjustments.
Conclusion: The RAS-Lung Project, employing innovative genotyping techniques, underscores the significance of comprehensive NSCLC genotyping. Tailored next-generation sequencing (NGS) and ctDNA monitoring may offer potential benefits in navigating the evolving landscape of KRAS-positive NSCLC treatment
Balancing sustainability and resilience in buildings: a resilience module for an existing sustainability rating system
The built environment is increasingly vulnerable to the frequent and severe hazards posed by climate change. Many existing buildings need to be more adequately equipped to withstand these threats, highlighting the need for adaptation strategies for new and existing building stock. Green building rating systems, developed and adopted since the 1990s, provide a framework for measuring sustainability; however, they largely lack the integration of resilience principles, indicating a critical gap in implementation. The primary objective of this PhD thesis is to develop a new Resilience Module, structured in a manner similar to existing building rating systems, and integrate it into the SBToolCZ framework, using this Czech national sustainability rating system as a case study. An extensive review of existing literature was conducted to identify recurring elements of sustainability and resilience in buildings. This informed the selection of relevant criteria and indicators for developing the Resilience Module. A weighting process was performed, with input from a panel of experts, to determine the significance of each criterion. The Resilience Module was tested as a standalone system on three building case studies located in the Czech Republic, assessing its effectiveness in measuring building resilience. Finally, the Resilience Module was integrated into the SBToolCZ rating system and tested in a building case study to compare the standard and integrated versions, demonstrating the feasibility and added value of the integration. The primary outcome of this research is a Resilience Module that can function independently as a tool for guiding designers toward more resilient projects while also being adaptable for incorporation into any green building rating system by integrating the criteria into existing categories. This work marks a significant advancement in incorporating resilience principles into building design, ensuring that both sustainability and resilience are considered, thereby enhancing the built environment's preparedness for future climate change-related hazards
Surveillance of antimicrobial resistance and healthcare-associated infections in veterinary teaching hospitals
The role of small animal veterinary hospitals in the onset and dissemination of antimicrobial-resistant organisms (AMROs) is an emerging research field, and the implementation of internal surveillance programs is a cost-effective tool to better understand their impact. The aim of this PhD project was to develop a surveillance program in the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Medical Sciences, University of Bologna, to obtain, analyze and compare data on AMROs and healthcare-associated infections (HAIs). The program was composed by passive surveillance, active surveillance on patients, active surveillance on the environment, outbreak surveillance and the communication system. Results from passive surveillance on 1342 clinical isolates highlighted a multi-drug resistance (MDR) percentage of 41.6%, with worrying non-susceptibility percentages detected for clindamycin (58.4%), amoxicillin-clavulanate (20.3%), piperacillin-tazobactam (15%) and enrofloxacin (45.8%). Whole genome sequencing on some selected MDR Enterobacterales isolates revealed the presence of multiple worrisome resistance genes, including the carbapenemase-encoding gene blaNDM-5. Considering only isolates from suspected HAIs (13.9% of the total), MDR percentage was considerably higher (71.7%). Active surveillance on patients showed a high in-hospital acquisition rate (25.6%) of commensal carbapenem-resistant gram-negative bacteria (CR-GNB) with multiple resistance genes, including blaNDM. Active surveillance on the environment detected high prevalence of methicillin- resistant Staphylococci (MRS, 19.5%). Active surveillance was also executed in a Spanish VTH, showing a lower AMROs frequency of detection at admission and in-hospital acquisition. Outbreak surveillance allowed to early detect and manage two outbreaks both caused by the Enterobacter cloacae complex. The communication system involved professionals from different fields and assisted the redaction of a new departmental biosecurity manual. Data collected from surveillance can serve as a basis to develop a tailored Infection Control Programs and underline the potential role of VTHs in the maintenance and dissemination of AMROs, including some considered highest priority for human medicine
Biofluid and neurophysiological biomarkers in amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis (ALS) is a fatal disease, characterized by the progressive degeneration of upper and lower motor neurons. There is an urgent need of biomarkers for a deeper understanding of the disease pathogenesis and for treatments discovery.
In this Ph.D. dissertation we aimed to explore the role of some biofluid biomarkers reflecting neurodegeneration, i.e. neurofilament light chain (NfL) and plasma p-tau phosphorylated at residue 181 (p-tau181), as well as others reflecting astrocitopathy (glial fibrillary acidic protein, GFAP).
We also investigated the prognostic role of conventional electromyography (EMG) in the bulbar region and the diagnostic value of a new method which estimates the number of motor units (MScanFit MUNE).
We confirmed that both cerebrospinal fluid (CSF) and plasma NfL showed a high accuracy in discriminating ALS patients from ALS mimics, and displayed an excellent prognostic value in detecting ALS patients with a faster disease progression and a shorter survival. Plasma p-tau181 values were found increased in ALS patients compared to controls, and resulted highly correlated with clinical and EMG lower motor neuron dysfunction. Furthermore, plasma GFAP increase in ALS was merely driven by amyloid-beta co-pathology and resulted well correlated with the cognitive profile of patients.
Exploring neurophysiological biomarkers, we demonstrated an excellent prognostic value of EMG genioglossus involvement, which resulted associated to a worse prognosis even in patients without clinical bulbar signs/symptoms.
A comparison between conventional quantitative EMG analysis and the novel MScanFit MUNE method did not reveal a better sensitivity of the second one in detecting abnormalities in the affected muscles. However, motor unit number estimation could be useful for monitoring ALS progression over time.
With these studies we produced several pieces of evidence which significantly contribute to this field of research in amyotrophic lateral sclerosis
Self-diagnostic and smart polymers based on fluorescent probes
This thesis explores luminescent molecules, including molecular rotors and aggregachromic dyes, integrated into polymer matrices to create self-diagnostic and smart polymers. Research spans mechanoluminochromism, temperature-dependent behavior, and sensitivity to free volume and chain mobility changes, providing insights into their dynamic interaction under diverse environmental conditions.
Using molecular rotors, the link between dye emission properties and matrix characteristics was deeply studied, challenging conventional assumptions. It is concluded that fluorescence lifetime is a more robust tool for discerning dye property changes than fluorescence intensity. An innovative approach measures chain mobility using a temperature-independent AIE probe, visualizing it with high resolution. Then, a phosphorescent probe explores free volume changes during stress-strain tests and aging, facilitating real-time monitoring.
Incorporating aggregachromic dyes aims to produce mechanoluminochromic materials sensitive to intermolecular distance and chromophore orientation changes. Bonding dyes to polymer chains versus blending is investigated.
Overall, this work provides insights into luminescent dye utilization within polymer matrices, offering versatility and sensitivity for applications like damage detection, load-bearing devices, and mechanochromic textiles, paving the way for future developments in polymer-based luminescent material