10081 research outputs found
Sort by
Methods and tools for enabling industrial symbiosis networks in the context of industry 4.0
No full textOver the past few decades, industrial practices have faced two significant shifts driven by digitalisation and sustainability: the advent of Industry 4.0 (I4.0) and the growing awareness towards environmental issues. Within this evolving landscape, Industrial Symbiosis (IS) has emerged as a key paradigm within the Circular Economy (CE). The aim of this dissertation is to propose innovative methods, models, and tools aided at integrating I4.0 technologies and digital tools in designing and managing IS networks (ISNs), to enhance resource circularity and promote sustainable practices across industrial ecosystems. The achievement of this primary goal is driven not only by a direct interest of modern industrial companies, but also by leading government councils such as the European Commission. Initially, this dissertation systematically investigates I4.0 technologies currently used in ISNs and assesses their potential for wider integration. This includes an in-depth review of the literature as well as case studies from various industrial sectors. The dissertation focus then shifts to tools that support businesses in developing industrial synergies, particularly during the critical early stages of engagement and commitment, and the later stages of effective implementation. To ensure their practical applicability, these tools were validated in real-world industrial contexts, including the industrial area of Bergamo, Italy, and the Kwinana Industrial Area (KIA) in Perth, Australia, chosen as representative sites due to their attractiveness in terms of industrial development and IS initiatives. Finally, the dissertation proposes a digital tool to assist users and practitioners in interpreting the results of an optimisation model for ISNs, displaying useful statistics for the strategic planning of new potential synergies. The research topics explored yield theoretical, methodological, and practical contributions that assist real-world industrial companies in addressing emerging trends
Exploring the incentive mechanisms for carbon farming contracts
No full textThere has been a recent increase in interest in carbon farming surging from newer forms of incentives that are being made available to farmers for enrolling into such schemes. With increased attention to defining carbon farming as a new business model, our thesis aims to define an efficient incentive mechanism that can be central to carbon farming contracts which will be profitable to the farmers and at the same time meet the environmental objectives of the scheme. We investigated the global carbon farming cases using a systematic mapping of literature, which was followed by analyzing the incentive mechanisms through the lens of carbon farming contract design attributes and project performance indicators using expert interviews, multi-criteria decision-making analysis, and qualitative inquiry. Key findings reveal that experts prefer hybrid incentive schemes (action-oriented) funded partially by public funding upfront (for covering farmers’ transaction cost, rewarding the co-benefits, and reducing risk) and partially by private sources, preferably by supply chain-based incentives (i.e., premium price for products) for outcomes, or by private market-based sources, that can be measured through simple low-cost monitoring and certified by public standards. Training and advisory, cooperation, and liability mechanisms should be intrinsic to the contract design to ensure permanence, additionality, and no leakage by implementing the project. We name this incentive mechanism the ‘hybrid-blend’ model, which parallels the EU regulations on carbon farming and meets the needs of the stakeholders involved, including, policy experts, government agencies, intermediaries, researchers, and financers. This incentive mechanism can also be applied to the voluntary carbon markets, as it addresses financial barriers like high transaction costs, the cost of complex monitoring systems, price volatility, and farmers’ risk management. Our research can provide insightful solutions to refining carbon farming contract designs, paving the way for the effective integration of carbon farming with climate mitigation goals
Advanced methods for the quantitative assessment of the safety of decarbonization technologies
No full textClimate change necessitates urgent action to reduce greenhouse gas emissions, with blue hydrogen emerging as a pivotal solution in the global energy transition. By utilizing Carbon Capture and Storage (CCS) to prevent CO₂ emissions and liquid hydrogen (LH₂) systems for efficient storage and transport, blue hydrogen bridges the reliance on fossil fuels and the adoption of renewable energy. However, these technologies pose significant safety challenges, including CO₂ toxicity, material erosion, cold embrittlement, cold burns, reduced seawater pH, LH₂ flammability, explosiveness, and risks from extreme cold. Addressing these risks is essential for the secure deployment and public acceptance of blue hydrogen technologies. This PhD thesis aims to enhance the understanding of safety in blue hydrogen technologies, focusing on accident scenarios in CCS and LH₂ facilities. It evaluates safety challenges, investigates the potential and limitations of existing risk management approaches, and develops advanced methods for assessing safety, reliability, and resilience. Key contributions include assessing inherent safety within blue hydrogen value chains, establishing the state of the art in risk assessment for CCS value chains, analyzing high-pressure CO₂ release consequences, evaluating experimental data on LH₂ releases, assessing the performance of safety barriers in LH₂ bunkering systems, exploring Natech threats and human errors in CCS and LH₂ facilities, and developing resilience models in the event of escalation scenarios triggered by domino effects. The study identifies gaps in existing quantitative risk assessment models and demonstrates the benefits of integrating probabilistic approaches and innovative strategies. It also highlights the importance of resilience and human reliability for thorough safety evaluations. Practical methodologies were tested through real-world case studies, offering valuable insights into offshore CCS systems and LH₂ handling. The findings provide a robust framework for enhancing safety in blue hydrogen technologies and inform future research directions, paving the way for a sustainable and secure energy transition
Integrated stress response and lipid remodeling are adaptive mechanisms triggered by Complex I deficiency in cancer cells
No full textRespiratory Complex I (CI) is a pivotal enzyme for cellular bioenergetics and its functional alterations trigger metabolic and molecular adaptive responses that help cancer cells survive despite the energetic deficit. Since such mechanisms are far from being completely understood, we exploited multiple cancer cell lines of different tissue origins lacking CI, in which we knocked out the core subunit NDUFS3 (NDUFS3-/-), to elucidate their response to energetic stress. During glucose restriction, NDUFS3-/- cells showed significant mitochondrial membrane depolarization, that in turn triggered the activation of the mitochondrial protease OMA1 leading to the processing of its targets, including those responsible for network fragmentation. These mitochondrial alterations were accompanied by a consistent activation of Integrated Stress Response (ISR) as proved by the phosphorylation of eIF2α, the block of protein synthesis, the nuclear re-localization of ATF4 and the increased expression of CHOP. These results were also observed in vivo and upon pharmacological CI inhibition by using EVP 4593. This molecular mechanism is responsible for the survival of CI-defective cells, and it is directed by OMA1 and suppressed when the protease expression is prevented. We also found that glucose deprivation triggered the accumulation of lipid droplets in close proximity to deranged mitochondria in CI-defective cells both in vitro and in vivo, accompanied by a profound alteration of lipid content, in particular we found an increase in triacylglycerols and in cholesteryl esters amount. In this context lipid droplets could sequester misfolded proteins, excess lipids and prevent free calcium overload in the cytosol in order to alleviate endoplasmic reticulum stress. In conclusion, loss of CI and glucose restriction induce a striking mitochondrial distress with depolarization and network fragmentation and trigger OMA1-mediated ISR to overcome the stress status and survive
Genomic, transcriptomic and metabolomic analysis of trisomy 21
No full textDown syndrome (DS) is caused by three copies of chromosome 21 (Hsa21). The pathogenetic mechanism underlying cognitive delay in individuals with DS is unclear, and there is no therapeutic strategy to improve this condition. In this work, the genotype-phenotype correlation was investigated in trisomy (T21) at the genomic, transcriptomic, and metabolomic levels to expand knowledge about the molecular mechanisms underlying the pathogenesis of DS. Two different research strategies were followed to approach this complex purpose. The first research strategy was to start from the sequence of Hsa21. The highly restricted-DS critical region (HR-DSCR) is the “minimal” region always associated with a diagnosis of DS in partial T21 cases and likely associated with DS “core” features, particularly intellectual disability (ID). We re-confirmed the HR-DSCR genomic limits, and we characterized the locus through in-silico and in-vitro gene expression analyses. We developed a new T21 cell model having a deletion of the HR-DSCR to re-establish the normal copy number of this region and study the phenotypic changes that this deletion resulted in. The second research strategy was to start from the metabolism, searching for alterations that could cause ID in DS. We focused on one-carbon metabolism, dosing central metabolite levels in the plasma and urine samples of DS and control groups, finding some dysregulated metabolic intermediates. The expression of genes involved in the one-carbon pathway was studied in silico using our previously published blood transcriptome map (DS vs control) and in vitro on a broader number of samples. Several differential expressed genes and statistically significant correlations emerged, confirming the complexity and the dysregulation of this pathway. Moreover, the quality of microarray-derived expression data was improved.
These results could strengthen our clinical trial proposal that rebalancing the one-carbon pathway through administering a metabolic intermediate to children with DS could improve their cognitive status
Unveiling novel oncogenic roles of CoREST complexes in high-risk neuroblastoma
No full textCoREST complexes, composed of LSD1, HDAC1/2, and RCoR1/2/3, are pivotal in neurodevelopment and have long been recognized as transcriptional repressors across various cancers. However, distinct roles of the three RCoR factors remain underexplored. Here, we unveil non-canonical functions of RCoR2 in MYCN-amplified neuroblastoma (NB), underscoring its unique significance compared to its paralogues. This novel insight shifts the paradigm, highlighting RCoR2 as a key determinant of NB chromatin landscape.
NB cell growth and tumorigenesis critically depend on RCoR1 and 2, with the RCOR2 gene exhibiting high histone acetylation levels and selective increased expression in NB. Unlike the well- known repressive roles of RCoR1, RNA-seq and ATAC-seq analyses demonstrate RCoR2 as a positive regulator of gene expression and chromatin accessibility. RCoR2 predominantly occupies active promoters and regions of open chromatin marked by H3K27ac and Pol2, defining its distinct binding pattern compared to RCoR1, which primarily targets enhancers.
Surprisingly, CoREST complexes co-occupy chromatin with NB core regulatory transcription factors (CRTFs), which positively drive NB-specific signatures. In particular, RCoR2, and not RCoR1, physically interacts with CRTFs and regulates their expression, implicating it as a new component of the adrenergic NB core regulatory circuitry (CRC). Mechanistically, H3K27ac and H3K4me2 levels are not drastically altered upon RCoR2 reduction, suggesting RCoR2 is not the primary driver of CoREST complexes’ catalytic activity. Instead, ATAC-seq data support a role of RCoR2 in sustaining chromatin accessibility and HiChIP data indicate that RCoR2 mediates chromatin looping, facilitating enhancer-promoter interactions and maintaining 3D chromatin architecture to sustain oncogenic transcriptional programs.
Based on these findings, we propose a model whereby RCoR2 promotes gene expression mediating contacts between CRTF-bound enhancers and their associated TSSs. Consequently, RCoR2 emerges as a critical vulnerability in high-risk neuroblastoma and a promising target for cancer therapeutics
Delivery systems for ocular surface and cornea disease treatments
No full textThis work demonstrates how the potential for overcoming the limitations of conventional treatments for ocular surface and corneal diseases may be achieved through the advancement offered by biomedical nanotechnology with the drug delivery systems. The opening section of the thesis presents an analysis of an etiological strand relating to ocular disorders. This is followed by an examination of the methodologies of loading and controlled release of protein molecules, with a view to restoring the loss of tear film homeostasis that occurs during certain ocular diseases. Conventional drug/substance administration to the ocular surface involves repeated drops of active ingredients and frequent, non-resolving pharmacological treatments. The present study explores the potential of a device constituted by two copolymers, loaded with lysozyme and lactoferrin, two proteins present in the tears of healthy patients, as a delivery system in a conjunctival application. First, the copolymers were synthesised and characterised from a molecular, thermal, structural and mechanical point of view. The characterisation included an analysis of the molecular structure, thermal properties, physical state and mechanical properties. The surface wettability was also evaluated. Subsequently, predetermined quantities of the active substance were loaded by melt-mixing, and the release kinetics from the polymeric matrices were studied. The results demonstrated that these materials allowed us to obtain a delivery system suitable for conjunctival tissue applications. In vitro cytotoxicity assays showed that both biomaterials supported growth of for 24h. Release analysis showed a gradual release over time of model proteins which kept their structure intact during the analyses. These properties make these materials promising candidates for ocular delivery treatments, especially for eye diseases that need frequent targeted administrations
Impact of deep brain stimulation on sleep-wake cycle in parkinson's disease and correlations between subcortical local field potentials and electrophysiological activity: a longitudinal study
No full textBackground: sleep disturbances in Parkinson’s Disease (PD) worsen motor and non-motor symptoms, but the impact of Deep Brain Stimulation (DBS) on sleep-wake cycles and subcortical sleep-related neurophysiology remains insufficiently explored.
Objectives: we investigated DBS’s effects on sleep architecture, circadian rhythm, and subcortical electrophysiological control in PD, with a focus on potential neurophysiological mechanisms for sleep modulation.
Methods: in our longitudinal study, 38 PD patients (9 females) undergoing DBS implants were evaluated with a thorough clinical evaluation, a 7-days actigraphy and video-polysomnography (vPSG) pre- and 6 months post-surgery. Patients implanted with a sensing enabled device performed synchronized local field potentials (LFPs) recording with actigraphy and vPSG. Repeated measures and linear mixed-effects models were used for statistical evaluation.
Results: following DBS, excessive daytime sleepiness levels decreased, significant increase in slow wave sleep with reduction of REM sleep motor events were observed. Actigraphy revealed increased nocturnal sleep consolidation with reduction of napping, and no modification of sleep fragmentation or circadian rhythms. Chronic evaluation of LFPs showed moderate correlations with motor activity and distinguished between diurnal wake and nocturnal sleep. LFPs also showed distinct subcortical oscillatory patterns across sleep phases: delta and theta oscillations reliably marked NREM stages, while beta and gamma patterns better defined REM. Specific frequency patterns were also found during arousals and distinguished REM sleep with and without atonia from actual REM sleep behavior disorder episodes, going beyond the predominance of beta band.
Conclusions: these findings underscore foundational neurophysiological insights that may inform future adaptive DBS (aDBS) interventions for sleep-related PD symptoms, emphasizing the need solidify this knowledge to fully develop DBS’s therapeutic potential in sleep regulation
Optimization of the grinding process on permanent magnets of high-performance electric motors
No full textThis thesis investigates the grinding process of two key automotive components: electric motor rotors and transmission gears. With the transition to electric mobility, stricter specifications and higher performance demands are shaping manufacturing processes, particularly for electric motors. The grinding of rare-earth permanent magnets (PMs) remains an underexplored field of growing technological interest, while gear grinding is well-established in the literature. Despite their different nature, both components were studied under dry conditions to minimize environmental impact by eliminating coolant usage. However, dry grinding poses challenges such as excessive heat generation, which can lead to surface burns, softening in gears, and magnetic property degradation in PMs.
Extensive testing was conducted first on individual PMs and then on complete rotors to determine optimal finishing parameters. This research, funded by Ferrari S.p.A., supports the development of a fully electric vehicle equipped with a motor featuring a rotor with rare-earth PMs (Nd₂Fe₁₄B). These magnets, produced through sintering, exhibit high hardness and brittleness, requiring careful assessment of process parameters (cutting speed and feed rate) and working conditions (wet vs. dry). Three material removal strategies were examined for PMs: grinding (tangential and cylindrical), face milling, and contour milling. Due to severe tool wear, milling proved unfeasible, but laser-assisted contour milling yielded promising results.
For gear grinding, an experimental analysis assessed the impact of process parameters on fatigue performance under wet and dry conditions. These tests were conducted within the FATECO project, funded by the European Commission, aiming to enhance the fatigue resistance of automotive components through eco-friendly finishing techniques. The findings confirmed the feasibility of dry grinding for both PMs and gears, identifying an optimal process window. However, conventional milling of PMs was impractical, whereas laser-assisted milling demonstrated notable industrial potential
Discourse markers in Spanish as a second language in Italian speaking migrants. Dynamics of acquisition and social interaction.
No full textQuesto studio analizza l’acquisizione dei segnali discorsivi (SD) in spagnolo L2 da parte di migranti italofoni a Madrid, considerando l’influenza delle abitudini linguistiche quotidiane e della rete sociale. Sono stati esaminati 20 informanti con storie linguistiche e migratorie differenti, attraverso interviste semi-strutturate, un questionario socio-biografico e un Discourse Completion Task (DCT). L’analisi si è focalizzata su tre SD ricorrenti (o sea, bueno, pues), valutandone la frequenza d’uso, le funzioni e i fenomeni di tag-switching. I risultati indicano che i partecipanti con maggiore interazione in spagnolo tendono ad avvicinarsi ai parlanti nativi in termini di frequenza d’uso dei SD. Tuttavia, solo pues mostra una correlazione positiva con la frequenza, la diversità funzionale e l’uso della L2, mentre bueno non presenta alcuna correlazione e o sea una correlazione negativa. I risultati sono stati interpretati in funzione di questioni legate alla fluency, a strategie di evitamento e come esiti di transfer pragmatici, specialmente nei casi in cui non era disponibile un equivalente diretto nella L1. Fattori individuali e contestuali emergono come ulteriori variabili influenti. Nel complesso, l’equivalenza con le forme della L1 risulta il principale fattore nell’acquisizione dei SD in spagnolo L2, mentre l’interazione sociale gioca un ruolo positivo ma marginale.This study examines discourse markers (DMs) in Spanish as a second language (L2) within the interlanguage of Italian-speaking migrants in Madrid, focusing on how linguistic practices and social networks shape their acquisition. Data were collected from 20 participants through semi-structured interviews, a socio-biographical questionnaire, and a Discourse Completion Task (DCT). The analysis targeted three frequent DMs in oral production (o sea, bueno, pues), investigating their frequency, functions, and tag-switching. Findings reveal that participants with greater exposure to Spanish approximate native speakers in DM frequency. However, only pues correlates positively with frequency, functional diversity, and L2 use, while bueno shows no correlation, and o sea a negative one. Fluency issues and avoidance strategies seem to impact DM use, especially when no direct L1 equivalent exists. Pragmatic transfer emerges, as participants tend to overextend DM usage based on L1 patterns. Individual variation and contextual factors also play a crucial role. Overall, L1 equivalence appears to be the primary factor influencing DM acquisition, with social interaction contributing positively but secondarily