Modeling hydrothermal system: deriving observables and hydrothermal instability in volcanic and non-volcanic setting

Hydrothermal fluids are a fundamental resource for understanding and monitoring volcanic and non-volcanic systems. This thesis is focused on the study of hydrothermal system through numerical modeling with the geothermal simulator TOUGH2. Several simulations are presented, and geophysical and geochemical observables, arising from fluids circulation, are analyzed in detail throughout the thesis. In a volcanic setting, fluids feeding fumaroles and hot spring may play a key role in the hazard evaluation. The evolution of the fluids circulation is caused by a strong interaction between magmatic and hydrothermal systems. A simultaneous analysis of different geophysical and geochemical observables is a sound approach for interpreting monitored data and to infer a consistent conceptual model. Analyzed observables are ground displacement, gravity changes, electrical conductivity, amount, composition and temperature of the emitted gases at surface, and extent of degassing area. Results highlight the different temporal response of the considered observables, as well as the different radial pattern of variation. However, magnitude, temporal response and radial pattern of these signals depend not only on the evolution of fluid circulation, but a main role is played by the considered rock properties. Numerical simulations highlight differences that arise from the assumption of different permeabilities, for both homogeneous and heterogeneous systems. Rock properties affect hydrothermal fluid circulation, controlling both the range of variation and the temporal evolution of the observable signals. Low temperature fumaroles and low discharge rate may be affected by atmospheric conditions. Detailed parametric simulations were performed, aimed to understand the effects of system properties, such as permeability and gas reservoir overpressure, on diffuse degassing when air temperature and barometric pressure changes are applied to the ground surface. Hydrothermal circulation, however, is not only a characteristic of volcanic system. Hot fluids may be involved in several mankind problems, such as studies on geothermal engineering, nuclear waste propagation in porous medium, and Geological Carbon Sequestration (GCS). The current concept for large-scale GCS is the direct injection of supercritical carbon dioxide into deep geological formations which typically contain brine. Upward displacement of such brine from deep reservoirs driven by pressure increases resulting from carbon dioxide injection may occur through abandoned wells, permeable faults or permeable channels. Brine intrusion into aquifers may degrade groundwater resources. Numerical results show that pressure rise drives dense water up to the conduits, and does not necessarily result in continuous flow. Rather, overpressure leads to new hydrostatic equilibrium if fluids are initially density stratified. If warm and salty fluid does not cool passing through the conduit, an oscillatory solution is then possible. Parameter studies delineate steady-state (static) and oscillatory solutions.

Quantifying and modeling ecosystem services provided by urban greening in cities of the Southern Alps, N Italy

Population growth in urban areas is a world-wide phenomenon. According to a recent United Nations report, over half of the world now lives in cities. Numerous health and environmental issues arise from this unprecedented urbanization. Recent studies have demonstrated the effectiveness of urban green spaces and the role they play in improving both the aesthetics and the quality of life of its residents. In particular, urban green spaces provide ecosystem services such as: urban air quality improvement by removing pollutants that can cause serious health problems, carbon storage, carbon sequestration and climate regulation through shading and evapotranspiration. Furthermore, epidemiological studies with controlled age, sex, marital and socio-economic status, have provided evidence of a positive relationship between green space and the life expectancy of senior citizens. However, there is little information on the role of public green spaces in mid-sized cities in northern Italy. To address this need, a study was conducted to assess the ecosystem services of urban green spaces in the city of Bolzano, South Tyrol, Italy. In particular, we quantified the cooling effect of urban trees and the hourly amount of pollution removed by the urban forest. The information was gathered using field data collected through local hourly air pollution readings, tree inventory and simulation models. During the study we quantified pollution removal for ozone, nitrogen dioxide, carbon monoxide and particulate matter (<10 microns). We estimated the above ground carbon stored and annually sequestered by the urban forest. Results have been compared to transportation CO2 emissions to determine the CO2 offset potential of urban streetscapes. Furthermore, we assessed commonly used methods for estimating carbon stored and sequestered by urban trees in the city of Bolzano. We also quantified ecosystem disservices such as hourly urban forest volatile organic compound emissions.

Motor control system in Parkinson’s disease: a modeling approach

Parkinson’s disease is a neurodegenerative disorder due to the death of the dopaminergic neurons of the substantia nigra of the basal ganglia. The process that leads to these neural alterations is still unknown. Parkinson’s disease affects most of all the motor sphere, with a wide array of impairment such as bradykinesia, akinesia, tremor, postural instability and singular phenomena such as freezing of gait. Moreover, in the last few years the fact that the degeneration in the basal ganglia circuitry induces not only motor but also cognitive alterations, not necessarily implicating dementia, and that dopamine loss induces also further implications due to dopamine-driven synaptic plasticity got more attention. At the present moment, no neuroprotective treatment is available, and even if dopamine-replacement therapies as well as electrical deep brain stimulation are able to improve the life conditions of the patients, they often present side effects on the long term, and cannot recover the neural loss, which instead continues to advance. In the present thesis both motor and cognitive aspects of Parkinson’s disease and basal ganglia circuitry were investigated, at first focusing on Parkinson’s disease sensory and balance issues by means of a new instrumented method based on inertial sensor to provide further information about postural control and postural strategies used to attain balance, then applying this newly developed approach to assess balance control in mild and severe patients, both ON and OFF levodopa replacement. Given the inability of levodopa to recover balance issues and the new physiological findings than underline the importance in Parkinson’s disease of non-dopaminergic neurotransmitters, it was therefore developed an original computational model focusing on acetylcholine, the most promising neurotransmitter according to physiology, and its role in synaptic plasticity. The rationale of this thesis is that a multidisciplinary approach could gain insight into Parkinson’s disease features still unresolved.

Modeling Alzheimer disease with iPSCs and mouse model for the identification of risk factors, new targets, and potential therapeutical strategies

Alzheimer's disease (AD) is the most common neurodegenerative disease in elderly. Donepezil is the first-line drug used for AD. In section one, the experimental activity was oriented to evaluate and characterize molecular and cellular mechanisms that contribute to neurodegeneration induced by the Aβ1-42 oligomers (Aβ1-42O) and potential neuroprotective effects of the hybrids feruloyl-donepezil compound called PQM130. The effects of PQM130 were compared to donepezil in a murine AD model, obtained by intracerebroventricular (i.c.v.) injection of Aβ1-42O. The intraperitoneal administration of PQM130 (0.5-1 mg/kg) after i.c.v. Aβ1-42O injection improved learning and memory, protecting mice against spatial cognition decline. Moreover, it reduced oxidative stress, neuroinflammation and neuronal apoptosis, induced cell survival and protein synthesis in mice hippocampus. PQM130 modulated different pathways than donepezil, and it is more effective in counteracting Aβ1-42O damage. The section two of the experimental activity was focused on studying a loss of function variants of ABCA7. GWA studies identified mutations in the ABCA7 gene as a risk factor for AD. The mechanism through which ABCA7 contributes to AD is not clear. ABCA7 regulates lipid metabolism and critically controls phagocytic function. To investigate ABCA7 functions, CRISPR/Cas9 technology was used to engineer human iPSCs and to carry the genetic variant Y622*, which results in a premature stop codon, causing ABCA7 loss-of-function. From iPSCs, astrocytes were generated. This study revealed the effects of ABCA7 loss in astrocytes. ABCA7 Y622* mutation induced dysfunctional endocytic trafficking, impairing Aβ clearance, lipid dysregulation and cell homeostasis disruption, alterations that could contribute to AD. Though further studies are needed to confirm the PQM130 neuroprotective role and ABCA7 function in AD, the provided results showed a better understanding of AD pathophysiology, a new therapeutic approach to treat AD, and illustrated an innovative methodology for studying the disease.

Physical modeling and numerical simulations of degradation mechanisms in devices and insulators for power applications

In this thesis, a TCAD approach for the investigation of charge transport in amorphous silicon dioxide is presented for the first time. The proposed approach is used to investigate high-voltage silicon oxide thick TEOS capacitors embedded in the back-end inter-level dielectric layers for galvanic insulation applications. In the first part of this thesis, a detailed review of the main physical and chemical properties of silicon dioxide and the main physical models for the description of charge transport in insulators are presented. In the second part, the characterization of high-voltage MIM structures at different high-field stress conditions up to the breakdown is presented. The main physical mechanisms responsible of the observed results are then discussed in details. The third part is dedicated to the implementation of a TCAD approach capable of describing charge transport in silicon dioxide layers in order to gain insight into the microscopic physical mechanisms responsible of the leakage current in MIM structures. In particular, I investigated and modeled the role of charge injection at contacts and charge build-up due to trapping and de-trapping mechanisms in the oxide layer to the purpose of understanding its behavior under DC and AC stress conditions. In addition, oxide breakdown due to impact-ionization of carriers has been taken into account in order to have a complete representation of the oxide behavior at very high fields. Numerical simulations have been compared against experiments to quantitatively validate the proposed approach. In the last part of the thesis, the proposed approach has been applied to simulate the breakdown in realistic structures under different stress conditions. The TCAD tool has been used to carry out a detailed analysis of the most relevant physical quantities, in order to gain a detailed understanding on the main mechanisms responsible for breakdown and guide design optimization.

Modeling of clear cell sarcoma of the kidney of the pediatric age

Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal tumor, characterized in 90% of cases by the presence of internal tandem duplications (ITDs) localized at the last exon of BCOR gene. BCOR protein constitute a core component of the non-canonical Polycomb Repressive Complex1 (PRC1.1), which performs a fundamental silencing activity. ITDs in the last BCOR exon at the level of PUFD domain have been identified in many tumor subtypes and could affect PCGF1 binding and the subsequent PRC1.1 activity, although the exact oncogenic mechanism of ITD remains poorly understood. This project has the objective of investigating the molecular mechanisms underlying the oncogenesis of CCSK, approaching the study with different methodologies. A first model in HEK-293 allowed to obtain important informations about BCOR functionality, suggesting that the presence of ITD generates an altered activity which is very different from a loss-of-function. It has also been observed that BCOR function within the PRC1.1 complex varies with different ITDs. Moreover, it allowed the identification of molecular signatures evoked by the presence of BCOR-ITD, including its role in extracellular matrix interactions and invasiveness promotion. The parallel analysis of WTS data from 8 CCSK cases permitted the identification of a peculiar signature for metastatic CCSKs, highlighting a 20-fold overexpression of FGF3. This factor promoted a significant increase in invasive ability in the cellular model. In order to study BCOR-ITD effects over cell stemness and differentiation, an inducible model is being obtained in H1 cells. This way, it will be possible to study the functionality of BCOR-ITD in a context more similar to the origin of CCSKs, evaluating both the specific interactome and phenotypic consequences caused by the mutation.