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Essays in Behavioural and Experimental Economics: Emotions, uncertainty and cooperation
No full textIn the present doctoral thesis I apply the experimental method in the context of two lines of research in Economics, the former investigating the role of incidental emotions in decision making under risk, whereas the latter shedding light on the impact of communication on cooperation. The dissertation consists of three sections. In the first chapter I conduct a laboratory experiment in order to study the effect of incidental sadness and happiness on risky decision making. An emotion induction procedure is the treatment variable of a between-subjects design where two sessions aim at eliciting either sadness or happiness, respectively. Two further groups are characterized by neutral conditions and serve as baseline. After a manipulation check verifies the validity of the induction procedure, I use a multiple price list `a la Holt and Laury (2002) to elicit individual risk preferences in the context of a lottery-choice task. The analysis reveals that both sadness and happiness promote greater risk aversion with respect to neutral conditions, a result which might be moderated by the risk elicitation task. Therefore, as effective explanation I propose the theory of ego depletion, whereby regulating emotions so as to subsequently process information consumes a limited self-control resource, which is needed to take risks as well. The second chapter is a meta-analysis of experimental studies on the same topic, so as to explain traditional heterogeneity of outcomes in the field. After performing an advanced search in Google Scholar and filtering out studies that do not match a list of selection criteria, I include 16 studies from which 46 observations are drawn at the treatment level. At this point, I code a set of moderator variables representing experimental protocols and calculate Cohen (1988)’s d effect size as dependent variable of a weighted least squares (WLS) regression where larger studies are given more weight. Among the results, which are robust to different techniques for computing standard errors, I find that emotions induce higher risk aversion when a multiple price list `a la Holt and Laury (2002) is used in place of stated preferences methods, as well as in case the risk elicitation task is framed as an investment decision instead of an abstract choice. Given the variety of procedures employed in this type of experiments and in the absence of a tailor-made game to answer such research questions, I recommend faithful study replication as preferential path in order to investigate the influence of emotions on risky decision making and ensure comparability. The third chapter offers evidence on the impact of communication on the provision of public goods whose quality is uncertain. I run a laboratory experiment with two treatments, where the control variable is pre-play communication in the form of unrestricted text chat. A binary threshold public goods game with four-person groups and threshold of three is at the core of the design, the main novelty lying in the provision mechanism with ambiguity. Moreover, a private signal for the actual value of the public good is provided, before the contribution decision. In accordance with related literature, I find that communication significantly increases public good provision by reducing inefficiency that comes from wasteful undercontribution. Nevertheless, the players in the chat treatment seem to neglect the free-rider issue and often end up overcontributing, in contrast with previous scientific findings. After chat analysis, I propose the pursuit of symmetric payoffs within the group as original explanation of the massive overcontribution, in addition to group identity generated by the partner matching and the common fate hypothesis. Since the players prefer to minimize ambiguity than to maximize the group earnings, I finally speculate that under uncertainty satisficing is more salient than optimizing
Molecular and functional characterization of the human RNASET2 oncosuppressor gene.
No full textThe RNASET2 gene maps to human chromosome 6q27, a region that has been consistently found rearranged in many solid and hematological tumors. This gene encodes for the only human secreted acid ribonuclease of the T2 family.
Our research group’s studies have demonstrated a remarkable RNASET2-mediated tumor suppressive activity. Indeed, we recently reported that the oncosuppressive activity of RNASET2 in vivo involves the recruitment toward the tumor mass of cancer-suppressive innate immune cells belonging to the monocyte/macrophage lineage, particularly M1 macrophages, which are known to carry out a cancer antagonizing role.
Given these premises, the aim of my PhD thesis work was to further characterize this gene from a functional point of view.
Firstly, we analyzed the effect of RNASET2 protein in the recruitment and polarization pattern of macrophages in in vitro systems.
Furthermore, since all previous in vivo experiments were performed using nude mice, we started developing a syngeneic mouse model in order to study the role of this gene in an immunocompetent model.
Finally, we recently demonstrated that RNASET2 also behaves as a stress response gene and strongly affects the actin cytoskeleton. To shed more lights on its pleiotropic functions, we also started to investigate the role of this gene in the context of mammary tumorigenesis and morphogenesis
Integrating phenotypes and endotypes in chronic rhinosinusitis: a combined clinical and experimental approach.
No full textChronic rhinosinusitis (CRS) represents a hot and debated topic in rhinology because of its high prevalence, heterogeneity of clinical manifestations and unpredictability of disease course. The quite recent dichotomic classification of CRS with and without nasal polyps has proved to be too simplistic to fully explain CRS manifestations and the underlying pathogenetic mechanisms. Being either the same phenotype expression of substantially different pathogenic mechanisms or different phenotypes the expression of the same mechanism, a one-size-fit-all therapeutic approach turned out to be insufficient in a non-negligible proportion of patients.
Moreover, considering the attempt of giving a classification cut at a biomolecular level, a diagnostic and prognostic approach exclusively limited to subjective and objective clinical parameters is inevitably failing in many ways. However, to date no other more effective markers are available to monitor the trend of the disease.
The fact of dealing with an apparently very frequent pathology responsible for a strong discomfort on the QoL and a substantial economic impact requires a diagnostic and therapeutic appropriateness for an adequate allocation of resources within the standards of precision medicine. The development of systems for a uniform archiving and sharing of the experiences of each rhinological center would enhance the efforts of the scientific community in defining integrated and targeted care pathways.
The present thesis reports the results and the practical implications of three different experimental studies about the implementation of data storage and sharing systems, methods of analysis of therapeutic outcomes and inflammatory biomarkers in CRS
Preliminar evaluation of epigenetic modifications followingi vitro hydroquinone exposure in models of human acute promyelocytic leukemia cells (HL-60) and of human umbilical cord mesenchimal stem cell (hUCMSC)
No full textBenzene, a volatile aromatic hydrocarbon, is extensively used in industry even though it is recognized as a myelotoxin with leukemogenic activity, representing a significant occupational risk. Metabolism of benzene plays a fundamental role in its toxicity, and among the different metabolites, hydroquinone (HQ) is one of the most important, as it accumulates in the bone marrow where it can induce several genetic and epigenetic changes. Nevertheless, the actual mechanisms behind the carcinogenetic effects of benzene and HQ and the role of epigenetic alterations in the process of tumorigenesis are not fully clarified yet.
Aberrant patterns of DNA methylation, including loss of imprinting (LOI), gene-specific hyper- or hypomethylation and global hypo-methylation are all common in several tumor types, including AML, and are important for transcriptional repression or activation of cancer-associated genes. Most of the studies on the epigenetic effects of benzene conducted so far have been centered on DNA methylation (measured on repeated elements LINE-1 and Alu, used as a surrogate for the entire genome), whereas only very recently a few investigations have analyzed the effects of environmental chemicals on histone modifications.
Several studies have shown a strong correlation between DNA methylation and histone modifications, indicating a cross-talk between DNMTs and histone modifications. For example, trimethylation of H3K27 (H3K27me3) can be associated with increased DNA methylation while de novo methylation does not occur in regions where bi-or trimethylation of the histone 3 lysine 4 (H3K4me2 or H3K4me3) is observed. Conversely, the simultaneous presence of H3K27me3 and H3K4me3 is recognized as a bivalent mark; it was firstly described during development and it appears to play a role in poisoning non-active genes for aberrant transcription in cancer.
Most notably, epidemiological studies on healthy subjects have shown a difference in the pattern of methylation between subjects exposed to benzene (gasoline station attendants) compared to office workers, with a significant reduction in the methylation of LINE-1 and Alu. This profile of global hypomethylation following exposure to low doses of benzene appears to be qualitatively comparable to what observed in AML and other neoplasms.
Thus, in the present work we attempted to reproduce in vitro the conditions of chronic exposure to benzene found in the peripheral blood of subjects exposed. We started from “low” doses of hydroquinone in vitro (below 15 μM) and we proceeded by progressively lowering the concentration to explore the cellular response to different types of exposure and concentrations, to evaluate if HQ might be able to alter the epigenetic signature in two different biological systems, thereby describing a poorly explored
step in the mechanism of toxicity associated with benzene exposure.
We finally set up a chronic treatment 4 weeks-long with HQ 1 μM, corresponding to 110 ng/mL, a concentration within the amount of total HQ (between 20 and 120 ng/mL, corresponding to 2–16 ng/mL of free HQ) found in the blood of subjects exposed to airborne benzene ranging from 1 mg/m3 (around 0,3 ppm) to 80mg/m3 (around 25 ppm). This concentration was used on a stabilized cell line of human acute promyelocytic leukemia (hAPML), HL60, analyzed as a model of hematopoietic cells; exploring the epigenetic events occurring in chromatin, we found the instauration of the distinctive signature combining the repressive H3K27me3 and the activating H3K4me3, with the gradual increase in H3K4me3 levels, on LINE-1 promoter region. We observed the absence of statistically significant variations in DNA methylation and expression levels of LINE-1, despite a decrease in protein levels of UHRF1, DNA methyl-transferases and histone methyl-transferases.
Moving onto a model of normal stem cells, we had to further lower the concentration to avoid cytotoxicity. Thus, human umbilical cord mesenchymal stem cells (hUCMSC) were treated for 4 weeks with HQ 0,1 μM to verify if long-term exposure to low doses of HQ could be able to alter the epigenetic signature in staminal cells outside the hematopoietic compartment. Surprisingly, we found a progressive increase of H3K4me3 in our control cells, with the instauration of the bivalent mark at the third week; the fourth week was non-evaluable, since the cytotoxic effect was prevalent despite the reduced concentration. Most interestingly, at the third week we observed the peculiar inversion in the levels of H3K27me3 and H3K4me3 on LINE-1 promoter region, with higher H3K27me3 in HQ treated cells as compared to the control, and opposite to what observed in HL60. On the other hand, as for HL60 cells no statistically significant variations in DNA methylation was appreciable. These differences were seen not only on chromatin but also on the profile of mRNA expression: preliminary Principal Component Analysis showed a significant distance between controls in the three biological replicates under consideration.
In conclusion, in vitro treatment with low-dose HQ determined the instauration of a poisoned state of chromatin in LINE-1 sequences in both the models considered, suggesting that prolonged exposure could cause persistent epigenetic alterations
Analogue Hawking radiation in Bose-Einstein condensates
No full textThis Thesis develops in the field of analogue gravity, a branch of physics which relies on a specific correspondence that exists between fluid dynamics and curved spacetimes; thanks to that, effects which are hard to study in the gravitational context are investigated in the realm of hydrodynamics with the hope that the consequent results could be transferred back to the cosmological domain and give us better insights in the gravitational context. In this Thesis, I try to introduce the reader to the realm of analogue gravity and to the concepts of Bose-Einstein condensation, Hawking radiation and its analogue counterpart (Chapter 1 and 2); then in Chapter 3 and 4 I describe the details of our work. In the past years, we have developed two directions of research, both aimed at the characterization of the analogue Hawking radiation in Bose-Einstein condensates. One side of our work had the purpose of investigating the results obtained in recent experiments apt to the detection of the analogue Hawking radiation in a quantum gas. Our results are very important in the description of the phenomena and give insights on how to develop future experiments (Chapter 3). The other side of our work aimed at the characterization of this effect from a theoretical point of view by means of an innovative approach, which allows for a much deeper and more detailed description of the radiation and helps shine new light on this effect (Chapter 4). In Chapter 5 we briefly discuss the possible developments of our studying, highlighting the missing pieces of this field and suggesting possible ways to approach the existing problems
Integrated multidisciplinary approaches to investigate geochemical anomalies in waters.
No full textWater is a fundamental need for human and environmental benefits, and its inorganic quality is a mandatory standard. Potentially Toxic Elements (PTEs), due to their high toxicity need to be evaluated. Consequently, in case of possibly alarming concentration, the causes (natural or anthropogenic) need to be clarified, to evaluate possible remediation techniques.
Integrated multidisciplinary approaches are needed to clearly understand causes of anomalous PTEs concentrations in waters, coupling chemical, hydrogeological and statistical tools, especially in a dynamic comportment as water.
In this dissertation integrated approaches will be applied to understand sources of anomalous concentrations of PTEs in waters. Firstly, PTEs sources in an alpine catchment are evaluated through the application multivariate statistics and the analysis of water and sediment to evaluate the natural load of PTEs.
Also, hydrogeochemical anomalies caused by a seismic sequence in Central Italy are explained through the application of a temporal trend analysis of hydrogeochemical and seismic variables. In this way, a conceptual model of PTEs release after the shocks is proposed.
The collection of these case studies highlights the need of a complete, integrated, and multidisciplinary approach to deal with geochemical data. These approaches still require a good knowledge of lithology and a big data set of chemical variables, but could fit as a first step to create leaching and transport models
The prototype phase of the ENUBET positron tagger
No full textUnderstanding the interaction of neutrinos with the other particles of the Standard Model is a fundamental activity in particle physics.
The uncertainties on the initial neutrino flux limit the sensitivity on the neutrino cross section measurement in the GeV range to a precision of 10-20%.
The scientific goal of the ENUBET project is to improve this sensitivity up to 1% by developing an active decay tunnel, as opposed to traditional neutrino beams, which have a passive decay region.
By tagging the positrons emitted in the Ke3 decay (K+ -> π0 + e+ + νe) it is possible to infer the initial neutrino flux. If the tunnel is short enough (about 50 m) the Ke3 decay is the only source of neutrinos.
Shashlik calorimeters are suitable to instrument such a tunnel, because they are cost effective, have a good geometrical adaptability and their energy resolution can be tuned with the proper absorbing/scintillator tiles thickness and fiber frequency. To separate the positrons from the pion background these calorimeters are longitudinally segmented with a compact readout based on Silicon PhotoMultipliers embedded in the bulk of the calorimeter itself.
This thesis describes the prototyping activity of the ENUBET Collaboration for the positron tagger and the tests performed at the CERN PS-T9 beamline from July 2016 to October 2017. The details of each prototype design and the results in terms of linearity and energy resolution are presented
Evaluation of a new ultrasonic device for surgical dissection in lung lobectomy and lymphadenectomy for lung cancer
No full textObjective
To assess and compare surgical electric hook vs Harmonic ACE Plus® impact on short-term postoperative outcomes after video-assisted thoracoscopic (VATS) lung lobectomy and lymphadenectomy for non-small cell lung cancer (NSCLC).
Materials and methods
We prospectively collected data of 120 consecutive patients [60% male; median age: 71 (62-76 IQR:) years] undergoing lung lobectomy and lymphadenectomy by VATS for NSCLC in our Center from October 1st 2016 to July 31th 2019. Patients were divided in two groups based on the device used for tissue dissection: the electric hook (Group A) in 68 cases and the Harmonic ACE Plus® (Group B) in 52. Multivariable analysis by binary logistic regression was performed in order to test the energy device as possible risk factor for pleural effusion volume at 48 hours after surgery and for postoperative chest tube duration.
Results
No intraoperative complications due to energy device were recorded in both groups.
Chylothorax incidence was higher in Group A with no statistically significant difference between the two groups (3% vs 0%; p-value=0.50). Pleural effusion volume during the first 48 postoperative hours was significantly higher in Group B: 253 ml (IQR: 149-405) vs 408 (IQR: 294-508) ml (p-value<0.01). However, chest tube duration was similar in the two groups: 4 (IQR: 3-8) vs 5 (IQR: 4-8) days (p-value=0.39). At multivariable analysis energy device was not independently associated with pleural effusion volume at 48 hours after surgery and with postoperative chest tube duration.
Conclusions
Electric hook or Harmonic ACE Plus® use during VATS lobectomy for NSCLC is safe and leads to similar postoperative short-term outcomes
Diketopiperazines as scaffold for the synthesis of new compounds modulating protein-protein interactions and functions
No full textmissin
Characterization of new synthetic or natural compounds with broad spectrum or dual antiviral activity in HIV-1 treatment
No full textIn recent years many advances have been made in the fight against HIV-1 infection. However, the lack of a vaccine, together with the increasing resistance to the highly active anti-retroviral therapy (HAART), make HIV-1 infection still a serious global emergency. Development of inhibitors that operate by a novel mechanism of action could expand the options for clinicians to address these unmet medical needs for the HIV-1-infected patient population or could represent novel options for an effective prevention.
In this contest, one possibility is the development of single drug with multiple targets binding, such as the natural compound kuwanon-L. Derived from the computational identification of novel potential allosteric inhibitors of HIV integrase, in this thesis kuwanon-L has been further characterised in enzymatic assays to evaluate its activity in vitro. Moreover, kuwanon-L was tested in cellular-based assays to confirm its antiviral activity also on viral strains. Finally, its mechanism of action was further investigated through a time-of-addition (TOA) experiment and its innovative dual mode of action on both HIV integrase and reverse transcriptase was confirmed in enzymatic assays.
On the other hand, compounds with novel mechanisms of action and targeting very early steps of viral life cycle, as the novel series of rhodanine derivatives investigated in the second part of this work, may represent potent anti-HIV-1 agents suitable for prevention approaches. Their activity not only on HIV but also on other sexually transmitted infections such as HSV-1/2 viruses, and their favourable pharmacokinetic profile further emphasize their usage as topical microbicides in pre-exposure prophylaxis (PrEP) approaches