University of Bologna

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    Design of integrated circuits for analog In-memory computing based on phase change memory

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    In the era of Artificial Intelligence (AI), numerous applications demand low-power computations involving large data volumes. Conventional digital computers face limitations due to the Von Neumann architecture, which necessitates continuous data transfers between memory and processing units. To overcome these constraints, novel computational approaches have been explored, including Analog In-Memory Computing (AIMC) based on resistive memory devices. AIMC has emerged as a promising non-Von Neumann solution for fast and energy-efficient Matrix-Vector Multiplication (MVM), a critical workload for deep learning inference. AIMC achieves substantial benefits in energy efficiency and speed by performing MVMs with O(1) time complexity. AIMC performs analog computations within resistive memory units by leveraging the physical properties of memory devices and exploiting Ohm’s and Kirchhoff’s laws. Phase-Change Memory (PCM) stands out for its ability to store multi-bit data long-term and its compatibility with CMOS fabrication processes. However, PCM devices face challenges such as non-linear I-V characteristics, random conductance drift, and variability in programmed cell states, which affect the accuracy of analog accelerators. This thesis explores these challenges and presents solutions for designing hardware accelerators using AIMC with PCM cells. Some hardware solutions are tailored to address PCM cell non-idealities but can be adapted for other AIMC systems. Results are supported by measurements from two prototype designs. The first prototype performs MAC operations with a computational architecture that includes reference cell conductance tracking (RCCT) to limit conductance drift effects on accuracy. The second prototype executes entire MVMs in one step, enhancing speed and power efficiency. Additionally, the thesis discusses a Bit Line Biasing circuit (BL-BC) designed to improve accuracy and energy efficiency, intended for a third prototype currently under fabrication. Finally, a programming procedure for PCM cells is presented to mitigate conductance drop and variability, involving current-induced heat-up to stabilize conductance, supported by experimental validation

    Between home and host: economic migrants’ perceptions of decent work

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    This dissertation investigates the Decent Work (DW) experiences of economic migrant workers in blue-collar roles, examining the challenges they face, how they interpret these challenges, and the resources that support their pursuit of a decent life and work. Framed by three interconnected studies, this research deepens our understanding of migrant workers’ experiences and contribute to the field of Work and Organizational Psychology. The first exploratory study examines the DW perceptions of migrant workers (N=137), addressing key dimensions such as Fundamental Principles and Values, and Health and Safety. Grounded in the Dual Frame of Reference theory and a Life-Course perspective, this study uses cluster analysis identifying disparities in work and life perceptions before and after migration and examines whether these differences shape migrants' perceptions of DW in the host country. The second study, grounded in Conservation of Resources theory, shifts focus to a specific organizational context by investigating the differential effects of DW on turnover intentions among migrant (N=144) and native (N=242) subgroups working in similar roles within the same company. Through a series of moderation analyses, this study highlights how migrant workers manage available resources (e.g., social connectedness) differently from their native coworkers, providing insight into the unique dynamics of resource gain and loss within the migrant workforce. The third study takes an in-depth qualitative, multi-actor approach, using interviews conducted with 31 respondents to understand how migrants and key host society actors perceive migrant working conditions in the Italian employment ecosystem. Drawing on Katz's conceptual framework of agency as resilience, reworking, and resistance, this study also examines migrants' agentic responses to precarious working conditions. Collectively, these studies offer a comprehensive view of the DW experiences of economic migrants, emphasizing the importance of tailored social support and intervention within the employment ecosystem to enhance well-being, integration, and retention among migrant workers

    Discovery, synthesis, and optimization of small molecules identified via multiple screening techniques for targeting cancer-related proteins

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    With the advent of genomic sequencing, our understanding of cancer has drastically improved, revealing unique molecular characteristics in each tumor that require tailored therapeutic approaches. Modern drug discovery methodologies such as Fragment-Based Drug Discovery (FBDD), DNA-Encoded Libraries (DEL), and virtual screening are revolutionizing precision oncology. This thesis first investigates Structure Activity Relationship (SAR) studies on compound 8, identified via 19F-NMR screening, which inhibits the RAD51-BRCA2 interaction—a key process in DNA repair—at micromolar potency. SAR analysis revealed that compound 8’s core structure is critical for activity, with derivatives showing significantly reduced potency. These findings provide a foundation for further optimization and structural analysis. The second part of this thesis explores work conducted during my research stay at Philochem AG on the application and development of DEL technology for diverse important oncology targets. Following Prof. Cavalli’s research focus, the RAD51-BRCA2 interaction was studied, yielding new binding hits and valuable insights into the rare application of DEL technology to DNA-binding proteins. DEL screenings also identified high-affinity, selective ligands for tumor-associated antigens, PSMA and CAIX, with compound 39 surpassing the gold standard acetazolamide in CAIX selectivity and biodistribution, and compound 59 outperforming the approved drug Pluvicto in PSMA selectivity. Additionally, a new ligand (compound 73) was validated for the immune target NKG2D, showing nanomolar binding affinity in vitro. To enhance DEL chemical diversity, this thesis also details work on optimizing DNA-compatible reactions, such as urea, thiourea, and sulfonamide formations, thereby expanding the chemical space accessible for ligand discovery. Finally, virtual screening was integrated with laboratory chemistry to discover novel TRAP1 inhibitors, a mitochondrial HSP90 chaperone linked to cancer metabolism. This effort led to the identification of a new class of allosteric inhibitors selective for TRAP1 over other HSP90 isoforms, currently undergoing biophysical and cellular evaluation

    How early life experiences shape the brain: behavioral and molecular insights

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    This thesis explores the profound effects of early life experiences on neurodevelopment, emphasizing the interaction between environmental factors and neuroplasticity. Early life adversity (ELA), including prenatal stress and inadequate maternal care, affects key stress-related neural circuits, particularly in the amygdala (AMY) and prefrontal cortex (PFC). These experiences can increase vulnerability to psychiatric disorders or promote resilience. Additionally, maternal factors, such as nutrition and substance use, significantly shape fetal brain development. The first aim was to investigate how early social environments influence emotional development and stress regulation, focusing on potential sex differences. Juvenile and adult Wistar rats were exposed to either early social isolation (ESI) from postnatal day (PND) 14-21 or communal nesting (CN), a supportive caregiving environment. Molecular assessments of glucocorticoid receptors (GR), cannabinoid receptor type-1 (CB1R), and fatty acid amide hydrolase (FAAH) in the PFC and AMY at PND 35 and PND 75 revealed significant behavioral, emotional, and molecular alterations. Results highlighted sexually dimorphic changes in CB1R expression and glucocorticoid levels, underscoring the importance of sex differences in neurodevelopmental outcomes. The second aim was to examine the effects of prenatal cannabinoid exposure (PCE) on offspring development. Using a novel vaping model to simulate cannabis inhalation, Long-Evans pregnant rats were exposed to THC (50 mg/mL) and CBD (5 mg/mL) from gestational day (GD) 5 to GD20. Behavioral and molecular analyses in offspring revealed significant disruptions in emotional and social behaviors, alongside alterations in AMY transcriptome and glucocorticoid signaling. These findings highlight the long-term impact of early life experiences on neurodevelopment, emphasizing the role of environmental and prenatal influences in shaping susceptibility to psychiatric disorders

    Calligraphy and performing arts in contemporary China: forty years of artistic expressions in performance, music and dance

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    This thesis explores the relationship between Chinese calligraphy and performance arts in contemporary China. It is divided into five chapters. The “Introduction” (Chapter 1) provides an overview of the research topic, objectives, methodology, and chapter structure. “Chinese Calligraphy and Performance Art – Exploring Ink Actions” (Chapter 2) examines the works of contemporary Chinese calligraphers and performers who use innovative approaches to combine calligraphy with performance art. This chapter discusses how body movements and calligraphic tools, such as ink, create dynamic works that explore the connection between gesture and writing. “Chinese Calligraphy and Music – Sounds of Ink” (Chapter 3) focuses on calligraphers who draw inspiration from music, creating performances that blend sound and visual elements into dynamic calligraphic-musical experiences. This chapter also examines musicians and composers whose works are inspired by calligraphy. “Chinese Calligraphy and Contemporary Dance – Arts in Movement” (Chapter 4) looks at dancers and companies who incorporate calligraphy into contemporary ballets, creating a dialogue between written art and physical movement. Finally, the “Conclusions” (Chapter 5) presents the findings of data analysis from the “WRITE Digital Archive,” a web-based semantic archive that collects and preserves the selected artworks. The analysis identifies trends and connections between calligraphy and the performing arts. This thesis demonstrates how calligraphy influences performance art, music, and dance, and how these art forms, in turn, enhance the expression of calligraphy, fostering a dynamic interaction between them

    ERBB and steroid hormone pathways in cell proliferation and differentiation

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    ERBB receptors are central to the development and progression of various tumours, including breast cancer. This study explored the role of ERBB ligands and receptors in basal-like/triple-negative breast cancer (TNBC), which is characterized by high EGFR and low ERBB2/HER2 expression. Using a quasi-normal basal-like/TNBC model, we found that ERBB2 and ERBB3 protein levels increase under anchorage-independent conditions, and their activation by Neuregulin 1 (NRG1) promotes spheroidogenesis, an effect counteracted by ERBB2-neutralizing antibodies. Similar findings were observed in malignant basal-like/TNBC cells, suggesting an oncogenic role for ERBB2/ERBB3 and their potential as therapeutic targets. Additionally, we observed that Neuregulin 4 (NRG4) activation of ERBB4 enhances the efficacy of anti-ERBB2 agents. It is noteworthy, however, that Neuregulin/ERBB2 signalling also plays a pivotal role in heart development and health; therefore, suppressing this pathway with anti-ERBB2 therapies could induce cardiotoxicity. Steroid hormones show a crosstalk with ERBB signalling, but whether they restrain spheroidogenesis induced by Neuregulins in breast cancer cells or their potential interference with cardiac NRG1/ERBB2 pathway leads to cardiotoxicity, warrants further investigations. In this regard, we aimed to investigate the impact of glucocorticoids on cardiomyocyte proliferation and cardiac health during the postnatal period, since in this developmental stage their role remains less defined. We found that corticosterone, the primary rodent glucocorticoid, restricts neonatal murine cardiomyocyte proliferation, whereas cardiomyocyte-specific Glucocorticoid Receptor (GR) deletion enhances it. Notably, GR ablation also improved heart regeneration following cardiac injury in adult mice, an effect mirrored by GR antagonism. Unexpectedly, corticosterone promoted proliferation in GR-ablated cardiomyocytes, likely through Mineralocorticoid Receptor (MR) activation, with preliminary findings identifying MR target genes involved in this proliferative effect. These opposite actions of corticosterone, anti-proliferative via GR and proliferative via MR, were also observed in adult human myocardial tissue, further supporting the importance of GR-MR balance in cardiomyocyte proliferation and cardiac health

    The sharing of group strategic vision and the attribution of value to training. A case study at the Istituto Romagnolo per lo Studio dei Tumori Dino Amadori in Meldola (FC) within the framework of the integrated competence system

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    Questa ricerca si inserisce in un più ampio progetto di sviluppo organizzativo volto a migliorare i processi di selezione, formazione e sviluppo professionale del personale attraverso l’implementazione di un sistema innovativo: il Sistema Integrato delle Competenze (SIC). Il SIC comprende diversi strumenti interconnessi, tra cui la Mappa delle Competenze, i Profili di Competenza Atteso e Attuale, l’Autovalutazione e i Dossier Formativi Individuali e di Gruppo. Lo studio esplora come il SIC favorisca l’emersione e la condivisione di una vision strategica di crescita all’interno dei gruppi professionali, contribuendo a una maggiore attribuzione di valore alla formazione e a un incremento della consapevolezza delle competenze individuali e del proprio ruolo nel gruppo. Gli obiettivi della ricerca sono due: (1) comprendere come i professionisti percepiscono il valore della formazione; (2) identificare i fattori che influenzano le scelte formative individuali e collettive. L’obiettivo finale è fornire evidenze utili a supportare l’adozione del SIC nell’allineamento tra sviluppo personale e strategie organizzative. La ricerca si basa su uno studio di caso con intervento realizzato presso IRST, coinvolgendo tre Unità Operative pilota per un totale di 28 professionisti. La raccolta dati ha incluso interviste semi-strutturate ai Responsabili di Unità, osservazioni di incontri di negoziazione e interviste finali ai membri dei gruppi. Un approfondimento è stato condotto sul Gruppo di Patologia Toracica per valutare le modifiche nelle percezioni e nei bisogni formativi. I risultati indicano che i professionisti attribuiscono maggiore valore alla formazione quando questa è chiaramente collegata a una vision strategica condivisa. Il SIC ha favorito una maggiore consapevolezza delle competenze e un rafforzamento dell’allineamento tra i bisogni formativi individuali e gli obiettivi del gruppo. Sebbene i risultati suggeriscano un potenziale di applicabilità più ampio, ulteriori studi sono necessari per confermare l’impatto del SIC in contesti sanitari differenti.This research is part of a broader organizational development project aimed at improving personnel selection, training, and professional development through the implementation of an innovative system: the Integrated Competence System (SIC). The SIC includes several interconnected tools, such as the Competence Map, Expected and Current Competence Profiles, Self-Assessment, and Individual and Group Training Dossier. The study explores how the SIC facilitates the emergence and sharing of a strategic growth vision among professional groups, fostering a greater attribution of value to training and increasing awareness of individual competencies and roles within the group. The research objectives are twofold: (1) to understand how professionals perceive the value of training; (2) to identify the factors influencing individual and collective training choices. The ultimate goal is to provide evidence supporting the adoption of the SIC in aligning personal and organizational development strategies. The study is based on an intervention case study conducted at IRST, involving three pilot units with 28 professionals. Data collection included semi-structured interviews with unit managers, observations of negotiation meetings, and final interviews with team members. A deeper analysis was conducted on the Thoracic Oncology Group to assess changes in perceptions and training needs. Findings indicate that professionals assign greater value to training when it aligns with a shared strategic vision. The SIC has enhanced awareness of competencies and strengthened alignment between training needs and group objectives. While results suggest the SIC’s potential for broader applicability, further research is needed to confirm its impact across different healthcare settings

    New biological insights from genomics and metabolomics in a livestock species: fostering applications to improve the sustainability of pig production systems

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    Biomedical science is becoming a data-driven discipline, thanks to the advent of high-throughput -omic technologies. The different layers of biological complexity are being explored, from the genomic layer, closest to the genetic background, to the phenomic layer, i.e. the full set of phenotypes for an organism. The link between genotype and phenotype is hard to establish directly, due to the influence of the environment and the various -omic layers. Metabolomics can act as a good proxy for this link, by representing a set of intermediate phenotypes that are closely related to both genotype and phenotype. In this thesis, we explore how genomics and metabolomics can be applied in animal science, in particular in pigs. After providing a summary of the state of the art of the field, we present our work in pig genomics and metabolomics. First, we explored in-depth the ABO gene using to a large collection of public and in-house produced whole genome sequencing datasets. The same datasets, along with a set of assembled genomes, were then used for a comprehensive analysis of nuclear insertions of mitocondrial sequences in the pig genome, to elucidate the complex and reticulate evolutionary history of pigs. We then moved to metabolomics to explain the differences in genetic background between two Italian pig breeds, using a large dataset of untargeted metabolomics data. The same dataset was finally used to explore the metabolomic differences between castrated males and females in Italian Large White pigs. In conclusion, we were able to leverage the hundreds of genomic datasets available to obtain a large scale picture of the porcine genome and its evolutionary history; the results of the metabolomic analyses could pave the way for a more precise description of the relationship between the genetic background of pigs with phenotypes and production traits of interest

    MEMS technology and Lab-on-a-Chip devices: exploring innovation in gas analysis and microtechnologies for heterogeneous catalysis studies

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    Micro-Electro-Mechanical Systems (MEMS) have revolutionized several scientific and industrial fields due to their unique ability to integrate mechanical and electrical functions at the microscale. In particular, MEMS technology has emerged as a critical driver of innovation in both micro gas chromatography (μGC) and heterogeneous catalysis, two fields that demand high precision, efficiency, and adaptability. In gas chromatography, the ongoing trend toward faster, more portable, and more efficient devices has seen MEMS-based systems become an essential tool in chemical analysis. The miniaturization of core components has enabled the creation of high-performance μGC systems that deliver rapid and accurate analyses, while significantly reducing the energy and space required for operation. Concurrently, MEMS-based microreactors have opened new possibilities in studying catalytic processes. These reactors, with their precise control over reaction conditions, scalable design, and intrinsic safety, offer unprecedented opportunities for exploring catalytic reactions and optimizing catalytic efficiency. This thesis investigates the design, development, and application of MEMS-based devices in the fields of gas analysis and heterogeneous catalysis. It presents novel approaches to the fabrication and integration of microcolumns and microreactors, emphasizing enhanced microcolumn integration while maintaining chromatographic resolution and catalytic performance. The research explores the adaptation of traditional fused silica columns to MEMS-based silicon and silicon-glass capillary columns, presenting experimental results and performance characterization. Novel wafer-level techniques such as pre-bonding deactivation and connection-free stationary phase deposition are introduced, improving scalability and integration into the commercially available micro gas chromatograph “PicoGC” from Pollution S.r.l. Additionally, a MEMS-based microreactor system is developed for studies in heterogeneous catalysis, with a case study on Thermochemical Water Splitting using CeO₂ nanorods. The study highlights operational advantages, including precise temperature modulation, and proposes hardware improvements and future research directions

    Methodologies and rapid procedures for damage assessment of historical buildings: the case of the 2012 Emilia earthquake.

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    Questo dottorato industriale nasce dalla collaborazione tra la Regione Emilia-Romagna, il Ministero della Cultura e l’Università di Bologna. L’obiettivo principale è stato quello di creare e ottimizzare un nuovo strumento di rilevamento dei danni da sisma da adottare durante le fasi emergenziali sui palazzi storici in muratura. Il modello proposto dal MIC, la "Scheda Palazzi B-DP", è stato ritenuto troppo complesso dalla Protezione Civile, per le situazioni di emergenza ed è stato sostituito dalla scheda AeDES, che, tuttavia, risulta troppo generica e semplificata per gli edifici storici in muratura. L’obiettivo del progetto di ricerca è stato quindi sviluppare una schedatura alternativa, informatizzata, ottimizzata e facile da compilare anche in condizioni di scarsa sicurezza, corredata da uno strumento per stimare a livello preliminare i costi di riparazione dei danni. Il valore aggiunto dell’informatizzazione consiste nella possibilità di precompilare la scheda acquisendo dati da sistemi GIS esistenti e trasmetterli in tempo reale all’Unità di Crisi e Coordinamento Regionale. La metodologia di ricerca ha incluso una revisione critica degli strumenti di schedatura esistenti, la proposta di una nuova schedatura, la stima preliminare dei costi di riparazione dei danni, e l'integrazione di questi strumenti con tecnologie digitali. Il modello di valutazione dei costi si basa sulla suddivisione dei palazzi in tre classi dimensionali, con l’obiettivo di fornire una stima preliminare dei costi di riparazione. Un test pilota condotto su 30 edifici ha mostrato una discrepanza di circa il 20% rispetto ad una prima valutazione degli stanziamenti effettuata nel 2012, pertanto il modello proposto può fornire una stima preliminare e approssimata ma rapida e oggettiva che potrebbe essere utilizzata nella fase di pianificazione per lo stanziamento delle risorse per la ricostruzione. In futuro, il sistema potrebbe essere adattato in contesti territoriali diversi e ampliato anche ad edifici in pietra, aumentando la flessibilità dello strumento.This industrial PhD project is the result of a collaboration between the Emilia-Romagna Region, the Ministry of Culture, and the University of Bologna. The primary objective was to create and optimize a new seismic damage assessment tool to be used during emergency phases on historic masonry buildings. The model proposed by the Ministry of Culture, the "Scheda Palazzi B-DP," was considered too complex by Civil Protection for emergency situations and was replaced by the AeDES form, which, however, is too generic and simplified for historic masonry buildings. Therefore, the aim of the research project was to develop an alternative, computerized, optimized, and easy-to-fill-out form, even in conditions of low safety, accompanied by a tool for the preliminary estimation of repair costs. The added value of the digitization process lies in the ability to pre-fill the form by acquiring data from existing GIS systems and transmitting it in real-time to the Crisis and Regional Coordination Unit, with the aim of supporting the post-earthquake reconstruction planning phase. The research methodology included a critical review of existing assessment tools, the proposal of a new form, the preliminary estimation of repair costs, and the integration of these tools with digital technologies. The cost assessment model is based on the division of buildings into three size classes, with the aim of providing a preliminary estimate of repair costs. A pilot test conducted on 30 buildings showed a discrepancy of about 20% compared to a first assessment of the allocations carried out in 2012, therefore the proposed model can provide a preliminary and summary but rapid and objective estimate that could be used in an initial planning phase for the allocation of resources for reconstruction. In the future, the system could be adapted to different territorial contexts, increasing the flexibility of the tool

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