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Sovereign wealth funds and state immunity
No full textThe study sheds light on the application of the rule of state immunity to sovereign wealth funds (SWFs). SWFs are Janus-faced investment vehicles established by their parent states to invest public resources in financial markets, with the aim of increasing long-term returns and pursuing macroeconomic goals. The ultimate purpose of the study is to assess if the hybrid nature of SWFs results in changes to the rule of state immunity when applied to them, and whether a generally accepted standard in this regard can be deduced from state practice.
The research is conducted through a comparative analysis. It is based on the provisions of the UN Convention on Jurisdictional Immunities of States and Their Property (UNCSI), as well as on six domestic jurisdictions (US, UK, France, Germany, Italy and China) among those that have contributed most significantly to the international debate on state immunity and which host the largest amount of SWF investments
Preharvest factors affecting quality and antioxidant levels on Abate Fétel pears: study of superficial scald with a multivariate statistical approach and neural networks
No full textThere are only a few insights concerning the influence that agronomic and management variability may have on superficial scald (SS) in pears. Abate Fétel pears were picked during three seasons (2018, 2019 and 2020) from thirty commercial orchards in the Emilia Romagna region, Italy. Using a multivariate statistical approach, high heterogeneity between farms for SS development after cold storage with regular atmosphere was demonstrated. Indeed, some factors seem to affect SS in all growing seasons: high yields, soil texture, improper irrigation and Nitrogen management, use of plant growth regulators, late harvest, precipitations, Calcium and cow manure, presence of nets, orchard age, training system and rootstock. Afterwards, we explored the spatio/temporal variability of fruit attributes in two pear orchards. Environmental and physiological spatial variables were recorded by a portable RTK GPS. High spatial variability of the SS index was observed. Through a geostatistical approach, some characteristics, including soil electrical conductivity and fruit size, have been shown to be negatively correlated with SS. Moreover, regression tree analyses were applied suggesting the presence of threshold values of antioxidant capacity, total phenolic content, and acidity against SS. High pulp firmness and IAD values before storage, denoting a more immature fruit, appeared to be correlated with low SS. Finally, a convolution neural networks (CNN) was tested to detect SS and the starch pattern index (SPI) in pears for portable device applications. Preliminary statistics showed that the model for SS had low accuracy but good precision, and the CNN for SPI denoted good performances compared to the Ctifl and Laimburg scales. The major conclusion is that Abate Fétel pears can potentially be stored in different cold rooms, according to their origin and quality features, ensuring the best fruit quality for the final consumers. These results might lead to a substantial improvement in the Italian pear industry
Moving toward stock units identification based on spatial population structure of marine species in the Mediterranean Sea and adjacent waters through multidisciplinary and holistic approaches for the sustainability of fisheries resources
No full textInvestigating stock identity of marine species in a multidisciplinary holistic approach can reveal patterns of complex spatial population structure and signatures of potential local adaptation. The population structure of common sole (Solea solea) in the Mediterranean Sea was delineated using genomic and otolith data, including single nucleotide polymorphisms (SNPs) markers and otolith data. SNPs were correlated with environmental and spatial variables to evaluate the impact of these features on the actual genetic population structure. Integrated holistic approach was applied to combine the tracers with different spatio-temporal scales. SNPs data was also used to illustrate the population structure of European hake (Merluccius merluccius) within the Alboran Sea, extending into the neighboring Mediterranean Sea and Atlantic Ocean. The aim was to identify patterns of neutral and potential adaptive genetic variation by applying seascape genomic framework. Results from both genetic and otolith data suggested significant divergence among putative populations of common sole, confirming a clear separation between Western, Adriatic Sea and Eastern Mediterranean Sea. Evidence of fine-scale population structure in the Western Mediterranean Sea was observed at outlier loci level and in the Adriatic. Our study not only indicates that separation among Mediterranean sole population is led primarily by neutral processes, but it also suggests the presence of local adaptation influenced by environmental and spatial factors. The holistic approach by considering the spatio-temporal scales of variation confirmed that the same pattern of separation between these geographical sites is currently occurring and has occurred for many generations. Results showed the occurrence of population structure in Merluccius merluccius by detecting westward–eastward differentiation among populations and distinct subgroups at a fine geographical scale using outlier SNPs. These results enhance the knowledge of the population structure of commercially relevant species to support the application of spatial stock assessment models, including a redefinition of fishery management units
Association between pre-treatment indicators and compliance to neoadjuvant/perioperative chemotherapy in operable gastric cancer
No full textBackground and aims: perioperative treatment is currently the gold standard approach for locally advanced gastric cancer (GC). Unfortunately, the phenomenon of patients dropping out of treatment has been frequently observed. The primary aims of this study were to verify if routine blood parameters, the inflammatory response markers, sarcopenia, and the depletion of adipose tissues were associated with compliance with neoadjuvant/perioperative chemotherapy.
Methods and study design: sarcopenia and adipose indices were calculated with a CT scan before starting chemotherapy and before surgery. Blood samples were considered before the first and second cycles of chemotherapy.
Results: A total of 84 patients with localized operable GC, were identified between September 2010 and January 2021. Forty-four patients (52.4%) did not complete the treatment according to the number of cycles planned/performed. Eight patients (9.5%) decided to suspend chemotherapy, seven patients (8.3%) discontinued because of clinical decision-making, 14 patients (16.7%) because of toxicity, and
15 patients (17.9%) for miscellaneous causes. Sarcopenia before starting chemotherapy was found to be present in 38 patients (50.7%) while it was in 47 patients (60%) at the CT scan before the gastrectomy. In multivariable analysis, both for changes tending to have a value of PLR at basal and in the second control a higher one than the cut-off (OR = 5.03, 95% CI: 1.34 - 18.89, p-value = 0.017), and for PLR which increased from a lower to a higher value in second control with respect to the cut off (OR = 4.64, 95% CI: 1.02 -21.02, p-value = 0.047) resulted associated with incomplete
compliance.
Conclusions: among the biological indicators, changes in the value of PLR with a tendency towards increasing compared to the cut-off appear to be an immediate indicator of incomplete compliance with neoadjuvant/perioperative treatment. More information is needed to reduce the causes of interruption
Cancers of unknown primary site (CUPs) as a model of metastatic process.
No full textCancers of unknown primary site (CUPs) are a rare group of metastatic tumours, with a frequency of 3-5%, with an overall survival of 6-10 month. The identification of tumour primary site is usually reached by a combination of diagnostic investigations and immunohistochemical testing of the tumour tissue. In CUP patients, these investigations are inconclusive.
Since international guidelines for treatment are based on primary site indication, CUP treatment requires a blind approach. As a consequence, CUPs are usually empiric treated with poorly effective.
In this study, we applied a set of microRNAs using EvaGreen-based Droplet Digital PCR in a retrospective and prospective collection of formalin-fixed paraffin-embedded tissue samples. We assessed miRNA expression of 155 samples including primary tumours (N=94), metastases of known origin (N=10) and metastases of unknown origin (N=50). Then, we applied the shrunken centroids predictive algorithm to obtain the CUP’s site(s)-of-origin. The molecular test was successfully applied to all CUP samples and provided a site-of-origin identification for all samples, potentially within a one-week time frame from sample inclusion.
In the second part of the study we derived two CUP cell lines, and corresponding patient-derived xenografts (PDXs). CUP cell lines and PDXs underwent histological, molecular, and genomic characterization confirming the features of the original tumour. Tissues-of-origin prediction was obtained from the tumour microRNA expression profile and confirmed by single cell RNA sequencing.
Genomic testing analysis identified FGFR2 amplification in both models. Drug-screening assays were performed to test the activity of FGFR2-targeting drug and the combination treatment with the MEK inhibitor trametinib, which proved to be synergic and exceptionally active, both in vitro and in vivo.
In conclusion, our study demonstrated that miRNA expression profiling could be employed as diagnostic test. Then we successfully derived two CUP models from patients, used for therapy tests, bringing personalized therapy closer to CUP patients
Exploring electric field applications in chemistry: a multiscale investigation
No full textElectric fields have gained a prominent role in modern chemistry. From the first spectroscopic investigations, through catalysis, to their role in solar cells, the application of electric fields at the interface with chemistry is the most diverse. The variety of applications of electric fields necessitates, when viewed from a theoretical standpoint, a set of methodologies for both modeling and simulation. This doctoral thesis reports three investigations exploring phenomena induced by electric fields, each one described with a distinct level of theory.
The thesis commences with the application of time-dependent perturbation theory to a transflection spectroscopy setup, a widely adopted approach for analyzing real samples, aiming to interpret the artifacts in the absorption spectra.
Subsequently, the thesis introduces a novel model for electrostatic catalysis. Electrostatic catalysis does not employ light, as traditional photocatalysis, but a static electric field. The model determines the amplitude and direction of the field for the optimal catalysis of a chemical reaction.
In its final investigation, the thesis employs a quantum model of the electric field to describe the formation of hybrid light-matter states and their catalytic effects on molecular isomerizations
Development of an in silico trial for the risk analysis of new hip replacement designs: predicting the risk of intraoperative fracture
No full textTotal Hip Arthroplasty is one of the most successful procedures, but, in the last years, the increase in the use of cementless stems has led to an increment of intraoperative femur fractures (3-5%), dependent on stem design. While numerous studies have investigated the mechanical behaviour of the femur during stem implantation through in vitro experiments, there is a notable lack of computational models specifically addressing IFF. This thesis aims to introduce a new approach for the numerical evaluation of IFF risk by using a simpler quasi-static and fully automated FE model capable of simulating crack propagation during stem insertion.
In the first part of the PhD project, eleven subject-specific FE models were built starting from CT data, and the implant pose and size of a non-commercial cementless stem were identified. A compressive load was applied along the stem axis to simulate the surgeon's hammering, while the femur was distally constrained. The element deactivation technique was used to simulate the crack propagation. Three additional damage quantification criteria were investigated to automatically establish when considered the femur fractured.
In the second part, the same workflow was repeated with a commercial stem design, but due to its geometry complexity, some modifications were introduced to the procedure. Additionally, a +/- one stem size uncertainty was introduced to investigate crack propagation under different canal-filling conditions.
In the last part, conducted at Zimmer Biomet, the work aimed to re-implement the developed algorithm in Abaqus. The crack propagation was modelled through a material properties degradation technique for assessing the risk of tibial bone fractures in two partial knee arthroplasty FE models. The crack path and final failure load obtained with FE analysis were compared with experimental results.
In conclusion, the project highlighted the algorithm's ability to simulate crack propagation with different implant designs
Evaluation of the prognostic role of inflammatory indices, tumor-infiltrating immune cells and molecular characteristics, in patients with localized soft tissue sarcoma.
No full textThis study aims to evaluate the ability of systemic and intratumoral immune status and some molecular features to predict a disease relapse inpatients affected by well and dedifferentiated liposarcoma (WDL, DDL), myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS).
Patients that received surgery and followed up at the IRST Istituto Romagnolo per lo Studio dei Tumori (Meldola, Italy) from 2010 to May 2020 were included. Information on blood counts were collected within a week before surgery. 71 FFPE samples were collected to perform an RNAsequencing, among these 47 samples were selected to perform a CIBERSORT analysis. A differential gene expression analysis was performed comparing G1 VS G2, G2 VS G3, G1 VS G3, Relapse VS No Relapse, Local relapse VS Distant metastasis, WDL VS DDL, MFS VS UPS.
Results 106 patients were included in this single-centre retrospective study.Patients had better RFS and OS when SSI < 991 ( P = 0,0001; P < 0,0001) NLR < 2,5 (P = 0,0006; P =0,0001), PLR < 190 (P = 0,0003; P < 0,0001), LMR ≥2,4 (P = 0,0067; P = 0,0011).According to the cluster analysis of intratumoral immune cells three major group are designed. The differential expression analysis has revealed five genes (SLC17A8, OR5M8, TIMM8BP2, SLC5A8, and HIST1H4K) that are overexpressed in patients with higher grading and disease recurrence.
ConclusionsThe findings of our study may define new biomarkers helpful in defining the risk class of STS patients if they’ll be validated in larger analysi
Circular and sustainable aquaculture: the use of next-generation protein sources in fish feed
No full textThe challenge of obtaining high-quality protein is increasing because of socio-economic factors and environmental concerns surrounding protein production, including greenhouse gas emissions and biodiversity loss. Consequently, there's a growing demand for sustainably produced proteins. Aquaculture plays a crucial role in meeting this demand, but it faces challenges related to the depletion of fish meal (FM) stocks, leading to sustainability and economic concerns.
During this doctoral research Hermetia illucens (HI) larvae meal and single-cell proteins (SCPs) from Torula yeast (TY) and Paecilomyces variotii (PV) were tested on gilthead sea bream. In the case of HI larvae meal, inclusion levels of up to 15% showed no negative effects on growth or feed efficiency. HI also positively impacted liver health and increased the abundance of beneficial gut microbiota. Additionally, it did not compromise the sensory, technological, or nutritional quality of sea bream fillets.
For TY, inclusion levels of 5% and 7.5% resulted in optimal growth performance, improved blood enzyme function under challenging conditions, and promoted beneficial gut microbiota. Similarly, inclusion of SCPs from PV did not affect growth performance and improved gut microbiota diversity and metabolic activity. Both TY and PV SCPs showed potential as alternatives to fish meal, with PV SCPs also demonstrating probiotic qualities.
In conclusion, HI larvae meal can effectively replace up to 15% of fish meal without compromising growth or feed efficiency, while also providing gut health benefits. TY and PV SCPs show promise as sustainable protein sources, with TY particularly beneficial at a 7.5% inclusion level. These findings underscore the potential of alternative protein sources to address sustainability challenges in aquaculture and warrant further investigation in this field
Studies on mitochondrial activity and bioenergetics in mammalian spermatozoa
No full textIntact mitochondrial activity is essential for mammalian spermatozoa metabolism and fertility; several artificial reproductive techniques may impair sperm function affecting mitochondrial activity and integrity. Cryopreservation, one of the most widely used ART for sperm preservation in bull have deleterious effects on sperm quality, particularly on mitochondrial activity. The main aim of this doctoral thesis dissertation is to define the features of mitochondrial function in cryopreserved bull semen, evaluate and define the best parameters to study by flow cytometry and fluorescence microscopy to evaluate mitochondrial activity and check if the red LED light irradiation process would be capable of increasing frozen-thawed bull sperm fertility. Different studies were carried out on cryopreserved bull semen and the main results indicate: that JC1 probe is the best marker of mitochondrial membrane potential; that mitochondrial function in frozen thawed bull spermatozoa is impaired, even if not completely; that the balance between oxidative phosphorylation and glycolysis allows bull sperm cells to obtain energy both if the processes are coupled or uncoupled, thus making sperm motility not strictly dependent on oxidative phosphorylation; that red LED light photostimulation of thawed bull semen increases oxygen consumption but doesn’t significantly improve mitochondrial coupling; that Red LED light photostimulation during the thawing process improves “in vivo” fertility when compared samples subjected to a standard protocol, but is not impactant on “in vitro” measured parameters. In conclusion, bull sperm cryopreservation induces mitochondrial damage, nevertheless, the function and fertility are maintained thanks to energy obtainment by glycolysis Photostimulation with LED light is a promising technique for imporving bull thawed sperm fertility, even if some insights are needed to understand the physiological mechanisms.L'attività mitocondriale intatta è essenziale per il metabolismo e la fertilità degli spermatozoi dei mammiferi; diverse tecniche di riproduzione artificiale possono compromettere la loro funzione influenzando l'attività e l'integrità mitocondriale. La crioconservazione, una delle TRA più utilizzate per la conservazione dello sperma di toro, ha effetti deleteri sulla loro qualità, in particolare sull’attività mitocondriale. Lo scopo principale di questa tesi di dottorato è definire le caratteristiche della funzione mitocondriale nel seme di toro crioconservato; valutare e definire i migliori parametri per valutare l'attività mitocondriale mediante citometria a flusso e microscopia a fluorescenza; e verificare se la fotostimolazione con luce LED rossa riuscirebbe ad aumentare la fertilità dello sperma di toro congelato-scongelato. Sono stati condotti diversi studi sul seme di toro crioconservato e i risultati indicano: che la sonda JC1 è il miglior marcatore del potenziale della membrana mitocondriale; che la funzione mitocondriale negli spermatozoi di toro congelati e scongelati è compromessa, anche se non completamente; che l'equilibrio tra fosforilazione ossidativa e glicolisi consente agli spermatozoi di toro di ottenere energia independenemente dello stato di disaccoppiamento dei mitochondri, rendendo la motilità degli spermatozoi non strettamente dipendente dalla fosforilazione ossidativa; che la fotostimolazione con luce LED rossa dello sperma di toro scongelato aumenta il consumo di ossigeno ma non migliora significativamente l'accoppiamento mitocondriale; che la fotostimolazione con luce LED rossa durante il processo di scongelamento migliora la fertilità “in vivo” rispetto a campioni sottoposti a un protocollo standard, ma non ha alcun impatto sui parametri misurati “in vitro”. In conclusione, la crioconservazione dello sperma di toro induce danno mitocondriale, tuttavia la funzione e la fertilità vengono mantenute grazie all’ottenimento di energia tramite glicolisi. La fotostimolazione con luce LED è una tecnica promettente per migliorare la fertilità dello sperma di toro scongelato, anche se sono necessari alcuni approfondimenti per comprenderne i meccanismi fisiologici