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Investigating the causes of late fruit drop in ‘Regina’ sweet cherry (Prunus avium)
The presented study aimed to correctly describe the (late) fruit drop pattern of sweet cherry cv. Regina grafted on ‘Gisela 5’ and investigate its internal causes.
In the first season, a method to describe the fruit drop pattern was defined and validated. The second season was devoted to a province-based screening of the phenomenon to identify potential influences of environmental, physiological and management factors. The multisite trial involved 6 commercial orchards located at different elevations, from 225 up to 1175m a.s.l. The third season was dedicated to find confirmation of the hypothesis formulated during the previous year. The multisite comparison was maintained but reduced to only two orchards to allow more frequent samplings.
It emerged that late fruit drop is a complex phenomenon showing variable intensity: the percentage of late fruit drop ranged from 7 to 76% of the fruitlets set, depending on the orchard and on the year considered. Two main waves of fruitlets drop have been observed: the first one was composed by unfertilized parthenocarpic fruitlets, probably caused by late or missing fertilization, that immediately after bloom already showed smaller diameters and symptoms of senescence; the second one (the focus of this study) was composed by fully developed fruits that at a certain point decreased their growth rate and got senescent. All the late dropped cherries showed an aborted embryo. This sudden change has been observed to be concomitant both with prolonged periods of low temperatures (or sudden severe decreases in the daily Growing Degree Hours accumulation) and with extraordinary high temperatures close to or above 30°C.
Other factors, such as the position of the limb within the canopy, its orientation (sunny vs. shady side) or nutrition played only a marginal role. Excessive vigor can increase late fruit drop intensity but is not its main cause
Essays in macroeconomics: insurance, market power, and inequality
This thesis investigates a broad range of topics related to insurance, market power, and inequality, both from an empirical and a theoretical perspective. In the first chapter, I exploit the significant heterogeneity of the shocks hitting Ethiopian households and their heterogeneous response, using relatively recent data (World Bank's LSMS-ISA for households and satellite data for weather shocks). On the one hand, households seem able to insure against most idiosyncratic and mild adverse weather shocks. On the other hand, vulnerability to stronger weather shocks (especially droughts) remains elevated. In the second chapter, starting from firms' individual data, aggregate trends about industry concentration and other proxies of competition are built. This chapter is part of a larger project conducted at the OECD in the Productivity Innovation and Entrepreneurship Division of the STI Directorate The project innovates on the existing literature in its measurement of concentration, aimed at reflecting markets more accurately. On average, aggregate concentration is found to be increasing. In the third chapter, which only lays out some preliminary steps of a more extensive inquiry, I model the heterogeneous effects of aggregate technological progress on individual economic agents and show how this can affect aggregate inequality and other aggregate indicators studied in the macroeconomics literature, such as the entrepreneurship rate and the overall firm distribution. It should be noted, however, that this note is a simple exposition of a possible modelling device rather than a full explanation of these phenomena
Analysis of efficacy and safety of CAR T-cell therapy in relapsed/refractory lymphomas: current indications and future perspectives
In the last few years, the introduction of chimeric antigen receptor (CAR) T-cell therapy into clinical practice has revolutionized the approach to patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), whose outcome used to be dismal with median overall survival (OS) of approximately 6 months with standard salvage therapy.
At our Institute, we started treating diffuse large B-cell lymphoma (DLBCL) patients with CAR T-cell products in August 2019 and they received either axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) as per regulatory indications. This research project presents the 2-year follow-up of the first 53 treated patients. Our first aim is to investigate the feasibility of this treatment strategy in a real-world setting, although the reimbursement criteria set by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) are very similar to the inclusion criteria of clinical trials and stricter than those established by the regulatory authorities of many foreign countries.
One month after infusion, the ORR was 66% with 19 patients already in CR (38%). Restaging at 3, 6 and 12 months post-infusion shows that early CRs tend to be maintained over time and, moreover, that a considerable number of PRs and a few SDs can improve into a CR. The safety data were consistent with what is reported in the literature; toxicity was generally manageable, largely due to the increasing expertise in handling the specific adverse events related to CAR T-cell therapy.
Our results confirms that CAR T-cell therapy is both safe and effective in a real-life setting and that it represents a crucial weapon in a subset of patients who were previously doomed to an inevitably severe prognosis
Porous margins: imaginaries on inner areas, migration, and inhabiting
Le aree interne, soggette ad un incessante processo di emigrazione fin dall'Unità d'Italia, rivestono oggigiorno un ruolo significativo nelle traiettorie della mobilità transnazionale e nell'accoglienza di migranti volontari e forzati. Nonostante il fenomeno sia strutturale, con ripercussioni talvolta positive sul welfare locale, non sono mai state avviate sinergie a livello nazionale tra l'ambito della riattivazione socio-territoriale e quello dell'accoglienza. Nelle narrazioni mediatiche e nell'immaginario collettivo, prevale un inquadramento emergenziale delle migraazioni ed uno statico dei contesti marginalizzati. Inserendosi in un ricco filone di studi sociologici che esplora la relazione tra mobilità umana ed aree in contrazione, la ricerca indaga i modi in cui la riattivazione socio-territoriale e la mobilità volontaria e forzata si relazionano, evidenziando le prospettive sull'abitare che ne emergono e concentrandosi sulle microstorie e sui posizionamenti multipli dei soggetti coinvolti. Vengono indagati diversi contesti con un focus sull'Appenino Meridionale, poco investigato nel dibattito accademico e pubblico nonostante sia significativamente interessato dai processi di contrazione ed accoglienza. I contesti individuati sono: i Comuni di Camini (Reggio Calabria), di Belmonte Calabro e di Amantea (Cosenza), di Entracque e di Chiusa di Pesio (Cuneo), di Biccari (Foggia), di San Severino Lucano e di Rotonda (Potenza). L'indagine ricorre a tecniche qualitative (interviste semi-strutturate, focus group, osservazioni partecipanti, mappatura, photovoice). Emerge che il mancato riconoscimento a livello nazionale della relazione tra i due ambiti faccia ricadere la responsabilità della sinergia sugli attori locali con esiti divergenti e ripercussioni sull'emplacement dei nuovi abitanti. Emerge inoltre come l'immaginario che permea l'abitare non sia definito dalla condizione di stanzialità ma dai processi di reciprocità e di appartenenza intesi come pratiche del fare insieme. Proponendo la cornice interpretativa della porosità, la ricerca mette in risalto le opportunità di dinamismo tra spazi e persone nelle aree interne, superando gli inquadramenti urbanocentrici che ne evidenziano invece le carenze.Inner areas, which have been subject to a never-ending process of emigration since the Italian Unification, nowadays hold a significant role in transnational mobility and reception of voluntary and forced migrants. Although a structural phenomenon, impacting sometimes positively on local welfare, there have never been synergies at the national level between socio-territorial reactivation and reception. Furthermore, an emergency framing of migration and a static framing of marginalized contexts prevail in media narratives and collective imagination. Within the context of a strand of sociological studies that has explored the relationship between human mobility and shrinking areas, this research investigates the ways in which socio-territorial reactivation and voluntary and forced mobility relate, highlighting the perspectives on dwelling that emerge and focusing on the micro-stories and multiple placements of those involved in the processes. Several contexts are investigated with a focus on the Southern Apennines, little investigated in academic and public debate despite the high incidence of both shrinking and reception processes. The identified contexts are: the municipalities of Camini, Belmonte Calabro and Amantea, Entracque and Chiusa di Pesio, Biccari, San Severino Lucano and Rotonda. The research makes use of multiple qualitative methods including semi-structured interviews, focus groups, participant observations, mapping and photovoice. It emerges that non-recognition at the national level of the relationship between the two spheres places the synergy responsibility on local actors resulting in divergent outcomes as well as impacts on the actual possibilities of emplacement for new inhabitants. It further emerges how the imaginary of dwelling in inner contexts is not defined by settledness but through processes of reciprocity and belonging understood as practices of making together. By proposing the interpretive framework of porosity to read territories at the margins, the research highlights opportunities for dynamism between spaces and people and overcomes urban-centric framings that instead highlight their deficiencies
An in vitro characterization of the bioenergetic effects of a phytosome-based Coenzyme Q10 formulation as a potential treatment for Troyer Syndrome
Coenzyme Q10 (CoQ10) plays a dual role in transferring electrons in the mitochondrial transport chain and acting as a membrane antioxidant. Due to its hydrophobic nature, several formulations have been developed to enhance its cellular uptake. We elucidated the bioenergetic and antioxidant effects of a CoQ10 phytosome formulation, UBIQSOME® (UBQ®) through two different studies. We investigated the potential benefits of UBQ® in I407 and H9c2 cells starting from the evaluation of cellular and mitochondrial content of CoQ10 and its redox state after UBQ® incubation. Oxygen consumption, ATP content, and mitochondrial potential were studied in UBQ® treated cells. The impact of UBQ® on oxidative stress, membrane lipid peroxidation, and ferroptosis was also investigated, highlighting the connection between CoQ10 concentration and its antioxidant efficacy. Furthermore, we explored the cellular mechanism regulating UBQ® internalization, revealing that the cell lines shared a common uptake mechanism, albeit with varying efficiency. In the second study, we demonstrated the crucial role of Spartin protein in nuclear-encoded mitochondrial proteins. Pathogenic Spartin variants are linked to Troyer syndrome, characterized by spasticity, weakness, short stature, cognitive impairment, and severe mitochondrial dysfunction. The identification of Spartin biallelic missense variants in a young patient with developmental delays and muscle weakness prompted further investigations. Patient-derived fibroblasts exhibited altered mitochondrial networks, decreased respiration, increased reactive oxygen species, and disrupted calcium dynamics compared to control cells. A mitochondrial protein import impairment was observed in fibroblasts and another cell model with a Spartin loss-of-function mutation, leading to a reduction in crucial CoQ10 synthesis enzymes and a drop in CoQ content. UBQ® supplementation and wild-type SPART re-expression equally restored ATP cell levels suggesting UBQ® treatment as a therapeutic approach for patients with Spartin mutations. This two different works highlight the intricate relationship between CoQ10 formulations, cellular bioenergetics, and the potential therapeutic impact in Troyer syndrome
Hardware-software co-design for large-scale structural health monitoring
Modern Structural Health Monitoring (SHM) systems currently utilize a combination of low-cost, low-energy sensors and processing units to monitor the conditions of target facilities. However, utilizing a dense deployment of sensors generates a significant volume of data that must be transmitted to the cloud, requiring high bandwidth and consuming substantial power, particularly when using wireless protocols. The current cloud-based solutions cannot scale if the raw data has to be collected from thousands of buildings. To optimize the energy budget and generated data of the monitoring system, it is crucial to reduce the size of the raw data near the sensors at the edge. However, existing compression techniques at the edge suffer from a trade-off between compression and accuracy and long latency, resulting in high energy consumption. This work presents a full-stack deployment of efficient and scalable data reduction and anomaly detection pipelines for SHM systems, which does not require transmitting raw data to the cloud but relies on edge computation. Three lightweight algorithmic approaches of anomaly detection are benchmarked, i.e., Principal Component Analysis (PCA), Fully-Connected AutoEncoder (FC-AE), and Convolutional AutoEncoder (C-AE) implemented on the SHM node. By doing so, network traffic decreases by ≈ 8 ・ 105×, from 780KB/hour to less than 10 Bytes/hour for a single node installation, and minimizes network and cloud resource utilization, enabling the scaling of the monitoring infrastructure. Finally, we propose our last SHM application to take a step forward in Traffic Load Estimation via the SHM system. This novel signal processing and classification pipeline is able to differentiate vehicles into three categories: light, i.e., less than 10 tons; heavy, i.e., between 10 and 30 tons; and super heavy, i.e., above 30 tons, using only features extracted from vibration data with an accuracy of 96%, utilizing the mean-shift, an unsupervised clustering model
Sustainable stnthesis and properties of CuS and application of its composites for degradation of organic compounds
Copper sulfide (CuS) is a p-type semiconductor, characteristic of high theoretical specific charge capacity, high concentration of charge carriers and excellent ability to absorb light. These properties lead to CuS application in the fields of photocatalysis, energy storage, or green hydrogen production. The ability of CuS to generate free charge carriers by absorbing the irradiation of visible light is harvested by applying CuS for the advanced oxidation process and the degradation of dyes or antibiotics. In particular, the presently mentioned organic molecules are widely known wastewater pollutants whose presence in the water cycle enhances the unexpected acceleration of antimicrobial resistance. However, a sustainable and cost-effective approach to synthesize copper sulfide is not fully developed. The formation of CuS in aqueous solution under hydrothermal conditions by using the waste of sulfuric acid production as secondary raw material of sulfur was investigated in this thesis. The morphology, thermal stability and photocatalytic properties of synthesized samples were also studied in this work. To apply synthesized material on a large scale for the degradation of organic pollutants, the bio composites from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and CuS were produced. The samples in porous and film structures were used to degrade tetracycline and methylene blue. The ability of composite to degrade organic molecules, be reused and degrade several organic molecules simultaneously was examined in this work
Integrated communication and learning towards autonomous mobile radio networks
The integration of distributed and ubiquitous intelligence has emerged over the last years as the mainspring of transformative advancements in mobile radio networks. As we approach the era of “mobile for intelligence”, next-generation wireless networks are poised to undergo significant and profound changes. Notably, the overarching challenge that lies ahead is the development and implementation of integrated communication and learning mechanisms that will enable the realization of autonomous mobile radio networks. The ultimate pursuit of eliminating human-in-the-loop constitutes an ambitious challenge, necessitating a meticulous delineation of the fundamental characteristics that artificial intelligence (AI) should possess to effectively achieve this objective. This challenge represents a paradigm shift in the design, deployment, and operation of wireless networks, where conventional, static configurations give way to dynamic, adaptive, and AI-native systems capable of self-optimization, self-sustainment, and learning. This thesis aims to provide a comprehensive exploration of the fundamental principles and practical approaches required to create autonomous mobile radio networks that seamlessly integrate communication and learning components.
The first chapter of this thesis introduces the notion of Predictive Quality of Service (PQoS) and adaptive optimization and expands upon the challenge to achieve adaptable, reliable, and robust network performance in dynamic and ever-changing environments. The subsequent chapter delves into the revolutionary role of generative AI in shaping next-generation autonomous networks. This chapter emphasizes achieving trustworthy uncertainty-aware generation processes with the use of approximate Bayesian methods and aims to show how generative AI can improve generalization while reducing data communication costs. Finally, the thesis embarks on the topic of distributed learning over wireless networks. Distributed learning and its declinations, including multi-agent reinforcement learning systems and federated learning, have the potential to meet the scalability demands of modern data-driven applications, enabling efficient and collaborative model training across dynamic scenarios while ensuring data privacy and reducing communication overhead
Network analysis and machine learning assist drug repurposing and safety assessment in neurological diseases
In recent decades, two prominent trends have influenced the data modeling field, namely network analysis and machine learning. This thesis explores the practical applications of these techniques within the domain of drug research, unveiling their multifaceted potential for advancing our comprehension of complex biological systems.
The research undertaken during this PhD program is situated at the intersection of network theory, computational methods, and drug research.
Across six projects presented herein, there is a gradual increase in model complexity. These projects traverse a diverse range of topics, with a specific emphasis on drug
repurposing and safety in the context of neurological diseases.
The aim of these projects is to leverage existing biomedical knowledge to develop innovative approaches that bolster drug research. The investigations have produced practical solutions, not only providing insights into the intricacies of biological systems, but also allowing the creation of valuable tools for their analysis. In short, the achievements are:
• A novel computational algorithm to identify adverse events specific to fixed-dose drug combinations.
• A web application that tracks the clinical drug research response to SARS-CoV-2.
• A Python package for differential gene expression analysis and the identification of key regulatory "switch genes".
• The identification of pivotal events causing drug-induced impulse control disorders linked to specific medications.
• An automated pipeline for discovering potential drug repurposing opportunities.
• The creation of a comprehensive knowledge graph and development of a graph machine learning model for predictions.
Collectively, these projects illustrate diverse applications of data science and network-based methodologies, highlighting the profound impact they can have in supporting drug research activities
Epidemiological studies on toxoplasma gondii infection in a one health perspective
The objective of the present Ph.D. thesis was to investigate with a One Health approach the epidemiological patterns of T. gondii infection in Italy, to better understand the transmission dynamics of the parasite, following different research lines. The results of a retrospective analysis in animals and human showed the widespread distribution of T. gondii in the study area, with specific antibodies found in various animal species and human populations, indicating its constant presence across diverse environments. The environment plays a significant role in T. gondii's epidemiology. Migratory aquatic birds, rodents, wolves, and wild boars were investigated as sentinels of their spread, highlighting the potential transmission across geographic areas and infection risks for wildlife in natural settings. The study also provided insights into seroprevalence in wolves. Dogs, subjected to serological investigations exhibited risk factors for T. gondii infection, such as cohabitation with cats, coprophagy behaviours, and continuous outdoor. Correlation between serological evidence of exposure to T. gondii and pathological anxiety in large-size dogs was observed, and the consumption of raw meat was associated with a higher risk of infection in these animals. Results of the investigations conducted in this thesis, demonstrate the dynamic nature of T. gondii infection in cattle, characterized by new infections and declining antibody levels over the production cycle. The study also describes a co-infection between T. gondii and Sarcocystis hominis in bovine eosinophilic myositis. In the final part of the Thesis, a comprehensive genotyping of T. gondii in Italy reveals the predominance of Type II strains, particularly in cases of ovine abortion and fatal toxoplasmosis among captive Lemur catta. This approach enhances our understanding of the parasite's genetic diversity and transmission patterns, vital for effective management of its impact on human and animal health in Italy