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Radio science experiments with the Hera mission
Get PDFThis thesis describes, designs, and develops the Hera Radio Science Experiment at the Didymos binary asteroid system. Hera represents the European Space Agency’s inaugural planetary defence space mission, and plays a pivotal role in the Asteroid Impact and Deflection Assessment international collaboration with the NASA DART mission that performed the first asteroid deflection experiment using the kinetic impactor technique. With the primary objective of conducting a detailed post-impact survey of the Didymos binary system following the DART impact on its small moon called Dimorphos, Hera aims to comprehensively assess and characterize the feasibility of the kinetic impactor technique in asteroid deflection while conducting in-depth investigation of the asteroid binary, including its physical and compositional properties as well as the effect of the impact on the surface and/or shape of Dimorphos. In this context, the Hera radio science experiment will allow to precisely estimate key physical parameters that are required to determine the momentum enhancement resulting from the DART impact, namely the mass, mass distribution, rotational states, relative orbits, and dynamics of the asteroids Didymos and Dimorphos. Through multi-arc covariance analysis the achievable accuracy for these parameters are
presented
How do macroeconomic conditions affect the party-policy relation? A study of pledge fulfilment in times of economic hardship
Get PDFThis project investigates how the economic performance of a country affects the policymaking process and the party-policy linkage. More specifically, this research focuses on periods of economic downturn and explores whether governing parties are able to prioritise the adoption of their policy preferences even in times of recession. Drawing on a literature that explores pledge fulfilment to determine the congruence between parties’ policy preferences and policies adopted, I investigate this topic using novel data on the realisation of electoral programs in Italy (1996-2018) and existing data on pledge fulfilment in seven democratic countries. By combining research on economic crisis with partisan and pledge studies, I argue that even though it is surely true that pledge fulfilment rates decrease during an economic downturn, partisan actors maintain a certain control over the policy implementation. Indeed, while a deterioration in the economic conditions of a country has a detrimental effect on public budgets, it might as well open up new opportunities and give parties new incentives, not least electoral ones, to carry out their policy proposals
Unveiling the dust-obscured activity of the universe through cosmic time: the view from the ALMA A3COSMOS survey
Get PDFThe derivation of statistical quantities, such as the LF and the SFRD, has allowed us to track how the overall galaxy population has undergone a transformation across cosmic time, both in demography and in typical luminosity. A significant fraction of the SFRD has come from dust-obscured sources. Thanks to the capability of ALMA to perform deep blind surveys in the mm/sub-mm it has been possible to study the evolution of dust obscured galaxies fainter than the sub-mm galaxies up to z~6, but these studies are limited by the small FOV of ALMA. To overcome this limitation, the A3COSMOS has been developed with the goal of collecting the ALMA archival images in the COSMOS field to perform statistical studies. In this Thesis, we present the method developed to homogenize the A3COSMOS collection of pointings, use them for statistical studies and for deriving evolutionary properties. Indeed, we were able to obtain the IR-LF of SF-galaxies from the A3COSMOS,, in a wide redshift range (0.5 2. To further investigate the properties of the A3COSMOS database, we derived the dust mass function and density up to z ∼ 6, finding a smooth decreasing trend in the dust mass density from z ∼ 1 to z ∼ 6. In future works, we plan to investigate more deeply the connection between galaxies and SMBHs evolution, by deriving the BHARD and by tracing its evolution over the redshift range covered by the A3COSMOS sample
Digital-based interventions for teams in the workplace
Get PDFThis research project investigated a digital workplace intervention based on team coaching and social network visualisation. The investigation was carried out through four studies. Study 1 was a systematic literature review with a realist synthesis approach about workplace digital interventions at multiple levels, highlighting the need for more research about group-level digital workplace interventions. Study 2 was a qualitative needs assessment exercise that verified the fit between the targeted organisations and the selected intervention. Following the tailored implementation of the intervention, Study 3 analysed recipients’ positive perceptions of intervention characteristics, with usability and integrity being appreciated the most, and acceptability being appreciated the least. While the intervention was considered usable and recipients felt valued during sessions, training did not fully meet their expectations. Also, recipients’ perceptions did not change from second to fourth session, suggesting they remained stably satisfied with the intervention over time. Finally, Study 4 tested two relevant Context-Mechanism-Outcome (CMO) configurations and suggested that teams implementing action plans developed during training might need less support from immediate managers to coordinate collective efforts and accomplish collective performance. Moreover, peer support towards training transfer was confirmed as a relevant contextual factor contributing to intervention effectiveness. Overall, this multifaceted and complex research project offers a nuanced examination of team-level digital interventions within the contemporary workplace, unveiling valuable insights and opportunities for further refinement and application
Gastrointestinal stromal tumors: Arbutus unedo L. as a source of novel chemotherapeutics & mechanisms behind metastasis
Get PDFGastrointestinal stromal tumors (GIST) are mesenchymal neoplasms frequently caused by a gain of function mutation in KIT or PDGFRα, two tyrosine kinase receptors (TKR). For this reason, they are successfully treated with imatinib, a tyrosine kinase inhibitor (TKI). However, the therapy is typically long-term ineffective due to imatinib resistance, which represents the main issue in the clinic of GISTs. Although numerous efforts have been made in the last two decades to develop novel therapies for imatinib-resistant GISTs, the approvals of multi-target TKIs have only improved the clinical outcomes modestly. Emblematic is the recent failure of ripretinib in the phase III INTRIGUE trial, decisively marking the end of the paradigm only based on the central role of KIT secondary mutations in imatinib resistance, and the consequent seeking of multi-target TKIs as the solution. Consistent with this clinical result, preclinical studies have revealed numerous mechanisms of resistance that are not targetable with multi-target TKIs, indicating that imatinib resistance is more multifaceted than initially hypothesized and explaining the modest efficacy of these latter. In this scenario, the absence of drugs capable of long-term counteracting the rise of imatinib-resistant subclones unavoidably leads to progressive disease and metastasis. In particular, the onset of metastases remarkably impacts the median overall survival and determines the most GIST-related deaths. Therefore, new therapy proposals are needed. Here, we present two project lines investigating novel strategies to counteract imatinib-resistant GISTs
Cardiac functional and structural abnormalities in a mouse model of CDKL5 deficiency disorder
Get PDFCDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a rare and severe neurodevelopmental disease that mostly affects girls who are heterozygous for mutations in the X-linked CDKL5 gene. The lack of CDKL5 protein expression or function leads to the appearance of numerous clinical features, including early-onset seizures, marked hypotonia, autistic features, and severe neurodevelopmental impairment. Mouse models of CDD, Cdkl5 KO mice, exhibit several behavioral phenotypes that mimic CDD features, such as impaired learning and memory, social interaction, and motor coordination. CDD symptomatology, along with the high CDKL5 expression levels in the brain, underscores the critical role that CDKL5 plays in proper brain development and function. Nevertheless, the improvement of the clinical overview of CDD in the past few years has defined a more detailed phenotypic spectrum; this includes very common alterations in peripheral organ
and tissue function, such as gastrointestinal problems, irregular breathing, hypotonia, and scoliosis, suggesting that CDKL5 deficiency compromises not only CNS function but also that of other organs/tissues. Here we report, for the first time, that a mouse model of CDD, the heterozygous Cdkl5 KO (Cdkl5 +/-) female mouse, exhibits cardiac functional and structural abnormalities. The mice also showed QTc prolongation and increased heart rate. These changes correlate with a marked decrease in parasympathetic activity to the heart and in the expression of the Scn5a and Hcn4 voltage-gated channels. Moreover, the Cdkl5 +/- heart shows typical signs of heart aging, including increased fibrosis, mitochondrial
dysfunctions, and increased ROS production. Overall, our study not only contributes to the understanding of the role of CDKL5 in heart structure/function but also documents a novel preclinical phenotype for future therapeutic investigation
Radiocarbon and stable isotopes in the shell organic matrix: a new approach for the use of mollusk shells in the study of human evolution
Get PDFMollusk shells are often found in archeological sites, given their great preservation potential and high value as a multipurpose resource. They are often the only available material to use for radiocarbon dating, due to a lack of well-preserved bones in many archeological sites, especially for the key period of the Middle to Upper Paleolithic transition. However, radiocarbon dating on mollusk shells is often regarded as less reliable compared to bones, wood, or charcoals due to the various factors influencing their radiocarbon content (e.g., Isotope fractionation, marine reservoir effect etc.). For the development of more accurate chronologies using shells, it is fundamental to continue improving the precision of the techniques applied, as has been done for other materials (wood and bones). Thus, improving the chemical pretreatment on mollusk shells might allow researchers to obtain more reliable radiocarbon determinations allowing for the construction of new radiocarbon chronologies in archeological sites where so far it has not been possible. Furthermore, mollusk shells can provide information on the climatic and environmental variables present during their growth. Using shells for paleoclimatic reconstruction adds more evidence helpful for the interpretation of scenarios of human migration, adaptation, and behavior. Standard methods for both radiocarbon and stable isotope studies use the carbonate fraction of the shell. However, being biogenic structures, mollusk shells also consist of a minor organic fraction. The shell organic matrix has an important role in the formation of the calcium carbonate structure and is still not fully understood. This thesis explores the potential of using the shell organic matrix for radiocarbon dating and paleoenvironmental studies. The results of the work performed for this thesis represent a starting point for future research to build on, and further develop the approach and methodology proposed here
Development and characterization of cutting-edge equipment for EMC measurements and advanced power line filter design
Get PDFThis Doctoral Thesis aims at studying, developing, and characterizing cutting edge equipment for EMC measurements and proposing innovative and advanced power line filter design techniques.
This document summarizes a three-year work, is strictly industry oriented and relies on EMC standards and regulations. It contains the main results, findings, and effort with the purpose of bringing innovative contributions at the scientific community.
Conducted emissions interferences are usually suppressed with power line filters. These filters are composed by common mode chokes, X capacitors and Y capacitors in order to mitigate both the differential mode and common mode noise, which compose the overall conducted emissions.
However, even at present days, available power line filter design techniques show several disadvantages. First of all, filters are designed to be implemented in ideal 50 Ω systems, condition which is far away from reality. Then, the attenuation introduced by the filter for common or differential mode noise is analyzed independently, without considering the possible mode conversion that can be produced by impedance mismatches, or asymmetries in either the power line filter itself or the equipment under test. Ultimately, the instrumentation used to perform conducted emissions measurement is, in most cases, not adequate. All these factors lead to an inaccurate design, contributing at increasing the size of the filter, making it more expensive and less performant than it should be
Study of the urinary biomarkers of synthetic cannabinoid receptor agonists (SCRAs) for the forensic unequivocal proof of consumption: medico-legal implications for drug abuse prevention
No full textIntroduction. Synthetic cannabinoid receptor agonists (SCRAs) represent the widest group of New Psychoactive Substances (NPS) and, around 2021-2022, new compounds emerged on the market. The aims of the present research were to identify suitable urinary markers of Cumyl-CB-MEGACLONE, Cumyl-NB-MEGACLONE, Cumyl-NB-MINACA, 5F-EDMB-PICA, EDMB-PINACA and ADB-HEXINACA, to present data on their prevalence and to adapt the methodology from the University of Freiburg to the University of Bologna.
Materials and methods. Human phase-I metabolites detected in 46 authentic urine samples were confirmed in vitro with pooled human liver microsomes (pHLM) assays, analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qToF-MS). Prevalence data were obtained from urines collected for abstinence control programs. The method to study SCRAs metabolism in use at the University of Freiburg was adapted to the local facilities, tested in vitro with 5F-EDMB-PICA and applied to the study of ADB-HEXINACA metabolism.
Results. Metabolites built by mono, di- and tri-hydroxylation were recommended as specific urinary biomarkers to monitor the consumption of SCRAs bearing a cumyl moiety. Monohydroxylated and defluorinated metabolites were suitable proof of 5F-EDMB-PICA consumption. Products of monohydroxylation and amide or ester hydrolysis, coupled to monohydroxylation or ketone formation, were recognized as specific markers for EDMB-PINACA and ADB-HEXINACA. The LC-qToF-MS method was successfully adapted to the University of Bologna, as tested with 5F-EDMB-PICA in vitro metabolites. Prevalence data showed that 5F-EDMB-PINACA and EDMB-PINACA were more prevalent than ADB-HEXINACA, but for a limited period.
Conclusion. Due to undetectability of parent compounds in urines and to shared metabolites among structurally related compounds, the identification of specific urinary biomarkers as unequivocal proofs of SCRAs consumption remains challenging for forensic laboratories. Urinary biomarkers are necessary to monitor SCRAs abuse and prevalence data could help in establishing tailored strategies to prevent their spreading, highlighting the role for legal medicine as a service to public health
EBV Type II latency relies on PARP1 activity and is essential for gastric epithelial cell transformation in EBV-associated Gastric Cancer (EBVaGC)
Get PDFEpstein-Barr virus (EBV) establishes a lifelong asymptomatic infection by replicating its chromatinized genome, called episome, together with the host genome. EBV exhibits different latency-associated transcriptional repertoires that mirror its three-dimensional structures of the genome. CTCF, Cohesin and PARP1 are involved in maintaining viral latency and establishing episome architecture. Epstein-Barr virus-associated gastric cancer (EBVaGC) represents almost 10% of all gastric cancers globally. EBVaGC exhibit an intermediate viral transcription profile known as "Latency II", expressing specific viral genes and non-coding RNAs. In this study, we investigated the impact of PARP1 inhibition on CTCF/Cohesin binding in Type II latency. We observed a destabilization of the binding of both factors, leading to a disrupted three-dimensional architecture of the episomes and consequently, an altered viral gene expression. Despite sharing the same CTCF binding profile, Type I, II, and III latencies display different 3D episomal structures that correlate with variations in viral gene expression. Additionally, our analysis of H3K27ac-enriched chromatin interactions revealed differences between Type II latency episomes and a link to cellular transformation through docking of the EBV episomes at specific sites of the Human genome, thus promoting oncogene expression. Overall, this work provides insights into the role of PARP1 in maintaining active latency and novel mechanisms of EBV-induced cellular transformation