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Numerical and physical modelling of axially loaded piles for offshore wind turbines
No full textThe scope of the thesis is to broaden the knowledge about axially loaded pipe piles, that can play as foundations for offshore wind turbines based on jacket structures. The goal of the work was pursued by interpreting experimental data on large-scale model piles and by developing numerical tools for the prediction of their monotonic response to tensile and compressive loads to failure. The availability of experimental results on large scale model piles produced in two different campaigns at Fraunhofer IWES (Hannover, Germany) represented the reference for the whole work. Data from CPTs, blow counts during installation and load-displacement curves allowed to develop considerations on the experimental results and comparison with empirical methods from literature, such as CPT-based methods and Load Transfer methods. The understanding of soil-structure interaction mechanisms has been involved in the study in order to better assess the mechanical response of the sand with the scope to help in developing predictive tools of the experiments. A lack of information on the response of Rohsand 3152 when in contact with steel was highlighted, so the necessity of better assessing its response was fulfilled with a comprehensive campaign of interface shear test. It was found how the response of the sand to ultimate conditions evolve with the roughness of the steel, which is a precious information to take account of when attempting the prediction of a pile capacity. Parallel to this topic, the work has developed a numerical modelling procedure that was validated on the available large-scale model piles at IWES. The modelling strategy is intended to build a FE model whose mechanical properties of the sand come from an interpretation of commonly available geotechnical tests. The results of the FE model were compared with other predictive tools currently used in the engineering practice
Assimilating artificial intelligence in organizations: a qualitative investigation of the adoption and implementation challenge
No full textArtificial Intelligence (AI) is predicted to contribute $15 trillion to the global economy by 2030, establishing it as a crucial General-Purpose Technology. However, the implementation of AI in businesses has not kept pace with the advancements in its research and the surrounding excitement. This has prompted the need for in-depth studies exploring the dynamics of its adoption and utilization by organizations. This dissertation contributes to the technology and innovation management literature with two main objectives: (1) identifying factors that influence organizations' decisions to adopt AI technologies and (2) examining how the technology implementation process is altered when organizations integrate AI. Initially, the research reviews existing models of technology adoption and implementation, pinpointing gaps in the current understanding of AI integration into business practices and advocating for new theoretical perspectives to comprehend its organizational impacts. Empirical investigation follows, based on primary data collected through exploratory interviews and multiple case studies, as detailed in Chapter 3. The findings, elaborated in Chapters 4 and 5, extend frameworks like Technology-Organization-Environment and Technology-Organization-People. The initial part of the research validates the importance of established factors such as relative advantage and management support, while also identifying unique AI-specific factors like the need for data infrastructure and technology understandability. The latter part of the dissertation delves into how AI implementation unfolds within companies. It reveals that the interplay between firms' implementation strategies, their relationship with AI vendors, and the gradual increase in AI awareness at various organizational levels significantly influences the implementation outcomes, moving beyond the simple dichotomy of success and failure. Overall, this work enhances our understanding of AI's role in organizational transformation and lays the groundwork for further academic and practical investigations
Anticancer drug-related cardiotoxicity from adjuvant goserelin and tamoxifen therapy
No full textThe ISACS cardiovascular toxicity is a pilot multicenter registry of breast cancer patients referred to hospitals for routine surveillance, suspected, or confirmed anticancer drug-related cardiotoxicity (ADRC). Patients may be enrolled retrospectively (1-year) and prospectively. The pilot phase focused on the available data on the combined Goserelin and Tamoxifen therapy for breast cancer and its impact on left ventricular (LV) disfunction at 1-year follow-up. Inverse probability of treatment weighting (IPTW) analysis of the ISACS registry assigning 70 patients to goserelin (3.6 mg subcutaneously once every 28-days), and tamoxifen (40 mg orally once daily) combined therapy. Controls consisted of 120 patients with no adjuvant combined goserelin and tamoxifen therapy. None of the patients developed distant metastasis. Primary tumor immunohistochemistry of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 was performed in all patients. Primary outcome measures were: low LV function in women as defined by an left ventricular ejection fraction (LVEF)<65% and subclinical LV dysfunction as defined by a 10-percentage point decrease of LVEF. In the overall population, combined goserelin and tamoxifen therapy did not affect the mean LV function compared with controls at 3, 6 and 12-month follow-up (65.7%±2.7% versus 65.3%±2.1%, P-value=0.27; 65.5%±2.9% versus 65.1%±2.5%, P-value=0.34; 65.0%±3.2% versus 64.6%±3.1%, P-value=0.29, respectively). The mean LVEF reduction in patients who did or did not receive combination therapy for 12 months was small and approximately similar (1.03%±2.5% versus 1.16%±2.9%, P-value=0.73). Using IPTW analyses, there was no significant associations between combined therapy and low LV function (risk ratio [RR]:1.75; 95%CI: 0.71–4.31) or subclinical LV dysfunction (RR:1.50; 95%CI: 0.35–6.53) compared with controls. One-year of endocrine therapy with goserelin and tamoxifen does not cause ADRC in patients with invasive breast cancer. Findings are independent of the severity of the disease. Results may not be definitive without replication in studies with larger sample size
Estimation of Jupiter's system ephemerides and dissipative parameters through radio tracking of deep space missions
No full textTidal dissipation is a key factor in creating mean motion resonance among satellites, particularly observed with Jupiter and its Galilean moons. This phenomenon is believed to drive the formation and potential dissolution of the Laplace Resonance, which has significant implications for the habitability of ocean worlds like Europa and Ganymede. The forthcoming JUICE and Europa Clipper missions will provide critical data by closely examining these moons, including more than 50 flybys of Europa and a prolonged orbit around Ganymede. These missions aim to gather precise measurements of the moons' gravity fields and orbits, enhancing our understanding of tidal dissipation within Jupiter. This dissipation is quantified through the imaginary part of the degree-2 Love numbers of the moons, which are complicated by the interconnectedness caused by the Laplace resonance. Additionally, the Io flybys by the Juno mission in December 2023 and February 2024, alongside historical data from the Galileo mission, will complement this dataset by providing insights into Io's role in the Jovian system's dynamics. Integrating this spacecraft data with over 120 years of ground-based astrometry will optimize the accuracy of dissipation parameter estimates in Jupiter, essential for understanding the long-term orbital dynamics of the Galilean moons, which may have characteristic frequencies spanning several decades
Pseudo-Anselme of Laon, Close in Apocalipsin. Critical edition and commentary
No full textLa tesi proposta offre l'edizione critica del commento all'Apocalisse attribuito ad Anselmo di Laon, ma con ogni probabilità pseudoepigrafo. Si tratta di un'esposizione trasmessa da otto testimoni in almeno due redazioni, una glossata e una in forma di testo continuo; per la prima di esse questa è l'editio princeps. Tale opera è nata nel contesto della scuola di Laon e rappresenta un punto di vista privilegiato per comprendere il cantiere di costruzione della Glossa ordinaria, il grande progetto culturale inaugurato da Anselmo di Laon all'inizio del XII secolo. Infatti, il testo documenta il nucleo originario della Glossa all'Apocalisse, prima della messa a punto della sua veste definitiva, avvenuta probabilmente a Parigi tra la fine del XII secolo e l'inizio del XIII, di cui l'esposizione pseudo-anselmiana rappresenta la fonte preponderante. Dell'opera sono descritte le vicende legate alla trasmissione manoscritta, l'edizione delle due redazioni e un ampio commento delle fonti, tra cui compaiono due esposizioni di poco anteriori ancora inedite. Un'introduzione colloca il commento nel contesto di produzione della Glossa ordinaria, di cui viene tracciato un profilo storiografico e un'analisi della sua genesi e dei temi portanti, ripercorrendone per punti lo stratificato percorso. L'ipotesi è verificata sull'Apocalisse.The proposed thesis offers a critical edition of the commentary on the Apocalypse attributed to Anselm of Laon, but most likely pseudoepigraphic. It presents an exposition transmitted by eight witnesses in at least two editions, one glossed and one in continuous text form; for the former, this is the editio princeps. This work originated in the context of the school of Laon and represents a privileged viewpoint for understanding the construction site of the Glossa ordinaria, the major cultural project inaugurated by Anselm of Laon at the beginning of the 12th century. In fact, the text documents the original nucleus of the Glossa on the Apocalypse, prior to the final development of its definitive form, which likely occurred in Paris between the end of the 12th century and the beginning of the 13th, of which the pseudo-Anselmian exposition represents the predominant source. The manuscript transmission events, the edition of the two editions, and a comprehensive commentary of the sources are described, including two previously unpublished expositions slightly earlier. An introduction situates the commentary in the context of the production of the Glossa ordinaria, providing a historiographical profile and an analysis of its genesis and main themes, tracing its layered trajectory point by point. The hypothesis is verified on the Apocalypse
Environmental pollutants and climate change in a One Health perspective
No full textL’obiettivo del primo studio è stato valutare gli effetti dell’esposizione materna a PFAS a catena corta (GenX e PFBA) sullo sviluppo neurologico nei ratti Sprague-Dawley. Attraverso un approccio sperimentale che includeva l’esposizione a diverse concentrazioni di contaminanti tramite la dieta, sono stati analizzati parametri comportamentali e molecolari per comprendere gli impatti a lungo termine su apprendimento e memoria. I risultati hanno mostrato un deterioramento delle capacità cognitive, associato a deficit nella neurogenesi e ad alterazioni del profilo tiroideo. Sono in corso ulteriori analisi per chiarire se tali effetti siano diretti o indiretti, mediante la valutazione dei residui di PFAS nei tessuti degli animali esposti. Il secondo studio ha avuto come scopo lo sviluppo e la validazione di un sistema in vitro basato su cellule staminali embrionali di ratto, per lo screening di tossicità su larga scala dei POPs. Utilizzando il disruptor endocrino TBBPA come composto modello, il sistema è stato in grado di riprodurre fasi critiche dello sviluppo embrionale, simulando il periodo pre- e post-impianto. I metodi hanno incluso la differenziazione neuroectodermica e l’analisi di meccanismi molecolari specifici, come l’interferenza con il segnale dell’ormone tiroideo. I risultati dimostrano la validità del modello come alternativa agli studi in vivo, fornendo un approccio innovativo per ridurre l’uso di animali negli studi di tossicità. Nel terzo studio, l’impatto delle ondate di calore è stato analizzato su Chamelea gallina, una specie di bivalve. Simulando condizioni di stress termico prolungato, sono stati misurati parametri fisiologici, biometrici e l’espressione della proteina HSP70 per valutare la risposta allo stress. I risultati indicano una resilienza significativa di questa specie, probabilmente legata all’adattamento al suo habitat mediterraneo. Tali evidenze suggeriscono che il settore della pesca di C. gallina potrebbe essere meno vulnerabile agli eventi di riscaldamento estremo previsti nel futuro.This dissertation, aligned with the PON program "Ph.D. programs on green themes", addresses the "Planet Health" perspective through three distinct investigations, exploring the environmental and health risks posed by persistent organic pollutants (POPs) and the effects of climate change on marine organisms. The first study evaluated the impact of maternal exposure to short-chain per- and polyfluoroalkyl substances (PFAS), specifically GenX and PFBA, on neurodevelopment in Sprague-Dawley rats. Employing an experimental approach involving dietary exposure to varying contaminant concentrations, behavioral and molecular parameters were analyzed to elucidate long-term effects on learning and memory. The findings revealed a discernible deterioration of cognitive abilities (learning and memory), associated with deficits in neurogenesis and alterations in the thyroid hormone profile. The second study focused on the development and validation of an in vitro system, based on rat embryonic stem cells, for high-throughput toxicity screening of POPs. The system successfully replicated critical stages of embryonic development, simulating both pre- and post-implantation periods, and was validated utilizing the endocrine-disrupting chemical tetrabromobisphenol A (TBBPA) as model compound. Methodologies included neuroectodermal differentiation and the analysis of specific molecular mechanisms, such as interference with hormone signaling. The results demonstrate the validity of this model as a promising alternative to in vivo studies, offering an innovative approach to reduce animal usage in toxicity assessments. The third investigation analyzed the impact of heatwave events on Chamelea gallina, a commercially important bivalve species. By simulating prolonged thermal stress conditions, physiological, biometric parameters, and the expression of the heat shock protein 70 (HSP70) were measured to evaluate the stress response. The findings indicate a significant resilience of this species, potentially linked to its adaptation to its Mediterranean habitat. These results suggest that the C. gallina fishing industry may exhibit less vulnerability to the extreme warming events projected for the future
Solving African mining industry puzzle through the lens of entrepreneurial harm
No full textThis research project sought to establish a comprehensive understanding of entrepreneurial harm through synthesising existing knowledge on it, theoretically evaluate the emergence of a violent form of harmful entrepreneurial behaviour and examine its interactions with emerging productive entrepreneurial behaviour in an industry. These objectives were achieved using an integrative literature review with data from thirty-three (33) years of published literature, a qualitative process study using press articles, interviews and industry data for 10 years and a fractional panel regression analysis, using over fifty-five thousand (55,000) mining license entries, satellite and press data as well as curated data on conflict events. The results offer profound contributions on the nature, evolution and results of entrepreneurial harm in a mining industry
Analytical evaluation of novel thermochemical-biological pathways for lignocellulose conversion into volatile fatty acids
No full textHybrid thermochemical-biological (HTB) biorefineries were recently proposed as a novel system for the conversion of lignocellulosic biomass into valuable products. This approach aims to couple the ability of thermochemistry to fast depolymerise refractory biomass into smaller molecules (e.g., pyrolysis), and the ability of microorganisms (e.g., microbial mixed cultures, MMC) to transform a variety of chemicals into a few targets products. Despite attempts were made to provide an evaluation of pyrolysis-anaerobic digestion (Py-AD), difficulties were found. These studies highlighted the need to increase the share of easily biodegradable molecules provided by thermochemistry to microbes. In this work, novel HTB pathways were proposed and analytically evaluated. Process flows were deeply investigated through a novel array of analytical techniques, providing a new chemical picture of different process combinations. Specifically, hydrothermal carbonization-intermediate/fast pyrolysis (HTC-Int-Py-AD and HTC-Fast-Py-AD), and slow pyrolysis-gasification (Py-Gs-AD) were evaluated in order to increase the delivery and quality of substrate within the thermochemical step. Gas and liquid products obtained through the proposed paths were biologically upgraded to volatile fatty acids (VFA). Results revealed an improved conversion of biomass into biological products, especially for the Py-Gs-AD route. The combination of hydrothermal carbonization and intermediate pyrolysis provided liquids with an increased share of sugars which resulted in fermentable, however did not significantly increase the overall yield of products with respect to the direct Py-AD. Noticeably, HTC-Fast-Py-AD path was found to be not suitable for the unequivocal higher toxicity of fast pyrolysis products with or without hydrothermal carbonization. The best results achieved were 50% chemical energy of biomass (on a chemical oxygen demand basis) converted into products within Py-Gs-AD pathway, and 40% of the latter with HTC-Int-Py-AD
Bioinformatic analysis of transposable elements reactivation and Topoisomerase I poisoning-induced double strand breaks in human cancers
No full textGenomic instability results from disruptions in key cellular processes like DNA replication, repair, transcription, chromatin remodeling, and cell cycle progression, leading to mutations and chromosomal abnormalities that contribute to tumorigenesis. Understanding its causes and effects is crucial for advancing cancer therapies. Features of genomic instability, like micronuclei and retrotransposon reactivation, are being used to improve the tumor microenvironment and support cancer immunotherapies by triggering immune responses and increasing lymphocyte infiltration in tumors.
This PhD project investigates the mechanisms inducing genomic instability and how to harness it for cancer therapy. The first part examines how transposable elements (TEs) activate an innate immune response in small-cell lung cancer (SCLC). Transcriptomic data reveals that TEs are deregulated in SCLC, and that their expression is suppressed in these cancers due to epigenomic silencing. This repression likely prevents their immune-stimulatory effects, making TEs potential targets for immunotherapy.
The second part explores the molecular basis of genomic instability induced by Top1 poisons, which stabilize Top1 cleavage complexes (Top1ccs). In colorectal cancer, Top1 poison treatment induces double-strand breaks (DSBs), especially in early-replicating regions of highly transcribed genes, leading to micronuclei formation and transcription-replication conflicts. Mutational analysis of metastatic colorectal cancer samples suggests that Top1 poisons are more likely to cause insertions/deletions in tumors, although further research is needed to assess their role in generating structural variations.
In conclusion, my PhD project provides insights into cancer genome instability mechanisms, their implications for tumor progression, and how they can be exploited for cancer immunotherapy
Multifaceted applications of crown ethers exploiting nitroxide labelling- cation sensing, synthesis of paramagnetic rotaxanes and dissipative processes of radical molecular machines
No full textCrown ethers are one of the most studied class of macrocycles for host-guest interactions. They have been employed in a wide range of possible applications in the field of biochemistry as biomimetic models, ionophores, metal sensing and mechanically interlocked molecules (MIMs). In the field of cation sensing an alternative approach consists in introducing radical probes as an active moiety in the complexation of a crown ether structure. In these systems, EPR spectroscopy acquires a key role in the detection of binding events thanks to its high sensitivity to the chemical environment surrounding the paramagnetic units. To this aim nitroxides based on aza-crown ethers were prepared and employed as selective sensors for the detection of inorganic and organic cations by EPR analysis of the corresponding host-guest complexes, particularly with Alkali, Alkali-earth and di-benzyl ammonium cations. The possibility to extend spin probe methodology in stable nitroxide macrocycle involved in molecular machines, like rotaxanes, makes the radical behaving as a direct recognizing unit for a guest hosted inside containing more than one station. In the present investigation, a [2]rotaxane based on a synthetic radical aza-crown ether derivative was studied in an aerobic oxidation reaction of alcohol to aldehyde as a mechanically blocked catalyst. Lastly, it is discussed a novel methodology for the synthesis of a series of 24-crown-8 chiral derivatives containing ethers, alcohols and carboxylic groups as side chains. Furthermore, these macrocycles were tested as catalysts for the synthesis of MGI-1 type Rotaxanes using the Metal-free active template approach, and the parameters to induct a face-selectivity of the macrocycles were also investigated