Modulation of epidermial growth factor receptor signaling in colon adenocarcinoma

The use of agents targeting EGFR represents a new frontier in colon cancer therapy. Among these, monoclonal antibodies (mAbs) and EGFR tyrosine kinase inhibitors (TKIs) seemed to be the most promising. However they have demonstrated low utility in therapy, the former being effective at toxic doses, the latter resulting inefficient in colon cancer. This thesis work presents studies on a new EGFR inhibitor, FR18, a molecule containing the same naphtoquinone core as shikonin, an agent with great anti-tumor potential. In HT-29, a human colon carcinoma cell line, flow cytometry, immunoprecipitation, and Western blot analysis, confocal spectral microscopy have demonstrated that FR18 is active at concentrations as low as 10 nM, inhibits EGF binding to EGFR while leaving unperturbed the receptor kinase activity. At concentration ranging from 30 nM to 5 μM, it activates apoptosis. FR18 seems therefore to have possible therapeutic applications in colon cancer. In addition, surface plasmon resonance (SPR) investigation of the direct EGF/EGFR complex interaction using different experimental approaches is presented. A commercially available purified EGFR was immobilised by amine coupling chemistry on SPR sensor chip and its interaction to EGF resulted to have a KD = 368 ± 0.65 nM. SPR technology allows the study of biomolecular interactions in real-time and label-free with a high degree of sensitivity and specificity and thus represents an important tool for drug discovery studies. On the other hand EGF/EGFR complex interaction represents a challenging but important system that can lead to significant general knowledge about receptor-ligand interactions, and the design of new drugs intended to interfere with EGFR binding activity.

Second law analysis and simulation techniques for the energy optimization of buildings

The research activity described in this thesis is focused mainly on the study of finite-element techniques applied to thermo-fluid dynamic problems of plant components and on the study of dynamic simulation techniques applied to integrated building design in order to enhance the energy performance of the building. The first part of this doctorate thesis is a broad dissertation on second law analysis of thermodynamic processes with the purpose of including the issue of the energy efficiency of buildings within a wider cultural context which is usually not considered by professionals in the energy sector. In particular, the first chapter includes, a rigorous scheme for the deduction of the expressions for molar exergy and molar flow exergy of pure chemical fuels. The study shows that molar exergy and molar flow exergy coincide when the temperature and pressure of the fuel are equal to those of the environment in which the combustion reaction takes place. A simple method to determine the Gibbs free energy for non-standard values of the temperature and pressure of the environment is then clarified. For hydrogen, carbon dioxide, and several hydrocarbons, the dependence of the molar exergy on the temperature and relative humidity of the environment is reported, together with an evaluation of molar exergy and molar flow exergy when the temperature and pressure of the fuel are different from those of the environment. As an application of second law analysis, a comparison of the thermodynamic efficiency of a condensing boiler and of a heat pump is also reported. The second chapter presents a study of borehole heat exchangers, that is, a polyethylene piping network buried in the soil which allows a ground-coupled heat pump to exchange heat with the ground. After a brief overview of low-enthalpy geothermal plants, an apparatus designed and assembled by the author to carry out thermal response tests is presented. Data obtained by means of in situ thermal response tests are reported and evaluated by means of a finite-element simulation method, implemented through the software package COMSOL Multyphysics. The simulation method allows the determination of the precise value of the effective thermal properties of the ground and of the grout, which are essential for the design of borehole heat exchangers. In addition to the study of a single plant component, namely the borehole heat exchanger, in the third chapter is presented a thorough process for the plant design of a zero carbon building complex. The plant is composed of: 1) a ground-coupled heat pump system for space heating and cooling, with electricity supplied by photovoltaic solar collectors; 2) air dehumidifiers; 3) thermal solar collectors to match 70% of domestic hot water energy use, and a wood pellet boiler for the remaining domestic hot water energy use and for exceptional winter peaks. This chapter includes the design methodology adopted: 1) dynamic simulation of the building complex with the software package TRNSYS for evaluating the energy requirements of the building complex; 2) ground-coupled heat pumps modelled by means of TRNSYS; and 3) evaluation of the total length of the borehole heat exchanger by an iterative method developed by the author. An economic feasibility and an exergy analysis of the proposed plant, compared with two other plants, are reported. The exergy analysis was performed by considering the embodied energy of the components of each plant and the exergy loss during the functioning of the plants.

Evaluation of Silver European EEL (anguilla anguilla) for the implementation of an Effective EEL Management plan in Mediterranean Coastal Lagoons

This thesis presents SEELF (Sustainable EEL fishery) Index, a methodology for evaluation of European eel (Anguilla anguilla) for the implementation of an effective Eel Management Plan, as defined by EU Regulation No.1100/2007. SEELF uses internal and external indices, age and blood parameters, and selects suitable specimen for restocking; it is also a reliable tool for eel stock management. In fact, SEELF Index, was developed in two versions: SEELF A, to be used in field operations (catch&release, eel status monitoring) and SEELF B to be used for quality control (food production) and research (eel status monitoring). Health status was evaluated also by biomarker analysis (ChE), and data were compared with age of eel. Age determination was performed with otolith reading and fish scale reading and a calibration between the two methods was possible. The study area was the Comacchio lagoon, a brackish coastal lagoon in Italy, well known as an example of suitable environment for eel fishery, where the capability to use the local natural resources has long been a key factor for a successful fishery management. Comacchio lagoon is proposed as an area where an effective EMP can be performed, in agreement with the main features (management of basins, reduction of mortality due to predators,etc.) highlighted for designation of European Restocking Area (ERA). The ERA is a new concept, proposed as a pillar of a new strategy on eel management and conservation. Furthermore, the features of ERAs can be useful in the framework of European Scale Eel Management Plan (ESEMP), proposed as a European scale implementation of EMP, providing a more effectiveness of conservation measures for eel management.

Fruit ripening/scald relationship in apple

The ripening stage of apple fruits at harvest is the main factor influencing fruit quality during the cold storage period that lasts several months and give rise to physiological disorders in fruits of susceptible cultivars. In particular, superficial scald is connected to α-farnesene oxidation, leading to fruit browning. Therefore, the assessment of the optimal ripening stage at harvest is considered to be crucial to control the overall quality, the length of storage life and the scald incidence. However, the maturity indexes traditionally used in the horticultural practice do not strictly correlate with fruit maturity, and do not account for the variability occurring in the field. Hence, the present work focused on the determination of apple fruit ripening with the use of an innovative, non-destructive device, the DA-meter. The study was conducted on ‘Granny Smith’ and ‘Pink Lady’ cultivars, which differ in scald susceptibility. Pre- and post- harvest ripening behavior of the fruits was studied, and the influence of ripening stage and treatments with 1-MCP were evaluated in relation to scald development and related metabolites. IAD was shown to be a reliable indicator of apple ripening, allowing cultivar-specific predictions of the optimal harvest time in different growing seasons. IAD may also be employed to segregate apple fruits in maturity classes, requiring different storage conditions to control flesh firmness reduction and scald incidence. Moreover, 1-MCP application is extremely effective in reducing superficial scald, and its effect is influenced by fruit ripening stage reached at harvest. However, the relation between ethylene and α-farnesene was not entirely elucidated. Thus, ethylene can be involved in other oxidative processes associated with scald besides α-farnesene regulation.

Innovative techniques for sport turf managing: Agronomic and phyisiological implications

The growing substrate of the putting greens is considered a key factor for a healthy turf ecosystem. Actually detailed study on the effects of growth promoting bacteria and biostimulants on a professional sport turf are very limited. This thesis aimed to study the effectiveness of different microorganisms and biostimulants in order to improve the knowledge relative to the relationship between the beneficial microflora and root apparatus of sport turfs. The research project was divided in three principal steps: Initially, commercial products based on biostimulants and microorganisms were tested on a Lolium perenne L. essence grown in a controlled-environment. The principal evaluations were the study of the habitus of plants, biomass production and length of leaves and roots. Were studied the capacity of colonization of microorganisms within root tissues and rhizosphere. In the second step were developed two different biostimulant solutions based on effective microorganisms, mycorrhizae and humic acids. This test was conducted both on an Agrostis stolonifera putting green (Modena Golf & Country Club) in a semi-field condition and within a growth chamber on a Lolium perenne L. essence. Fungicide and chemicals applications were suspended in order to assess the effectiveness of the inoculants for nutrition and control of pests. In the last step, different microorganism mixes and biostimulants were tested on an experimental putting green in the Turf Research Center (TRC) (Virginia Tech, United States) in a real managing situation. The effects of different treatments were studied maintaining all chemicals and mechanicals managements scheduled during a sport season. Both growth-chamber and field results confirmed the capacity of microorganisms based biostimulants to promote the physiologic conditions of the plants, improve the growth of the roots and enhance the aesthetic performance of the turf. Molecular analysis confirmed the capacity of microorganisms to colonize the root tissues.

Effective field theories and their phenomenological applications

Effective field theories (EFTs) are ubiquitous in theoretical physics and in particular in field theory descriptions of quantum systems probed at energies much lower than one or few characterizing scales. More recently, EFTs have gained a prominent role in the study of fundamental interactions and in particular in the parametriasation of new physics beyond the Standard Model, which would occur at scales Λ, much larger than the electroweak scale. In this thesis, EFTs are employed to study three different physics cases. First, we consider light-by-light scattering as a possible probe of new physics. At low energies it can be described by dimension-8 operators, leading to the well-known Euler-Heisenberg Lagrangian. We consider the explicit dependence of matching coefficients on type of particle running in the loop, confirming the sensitiveness to the spin, mass, and interactions of possibly new particles. Second, we consider EFTs to describe Dark Matter (DM) interactions with SM particles. We consider a phenomenologically motivated case, i.e., a new fermion state that couples to the Hypercharge through a form factor and has no interactions with photons and the Z boson. Results from direct, indirect and collider searches for DM are used to constrain the parameter space of the model. Third, we consider EFTs that describe axion-like particles (ALPs), whose phenomenology is inspired by the Peccei-Quinn solution to strong CP problem. ALPs generically couple to ordinary matter through dimension-5 operators. In our case study, we investigate the rather unique phenomenological implications of ALPs with enhanced couplings to the top quark.

The interplay of multiplicity and effective energy for (multi) strange hadron production in pp collisions at the LHC

The enhanced production of strange hadrons in heavy-ion collisions relative to that in minimum-bias pp collisions is historically considered one of the first signatures of the formation of a deconfined quark-gluon plasma. At the LHC, the ALICE experiment observed that the ratio of strange to non-strange hadron yields increases with the charged-particle multiplicity at midrapidity, starting from pp collisions and evolving smoothly across interaction systems and energies, ultimately reaching Pb-Pb collisions. The understanding of the origin of this effect in small systems remains an open question. This thesis presents a comprehensive study of the production of $K^{0}_{S}$, $\Lambda$ ($\bar{\Lambda}$) and $\Xi^{-}$ ($\bar{\Xi}^{+}$) strange hadrons in pp collisions at $\sqrt{s}$ = 13 TeV collected in LHC Run 2 with ALICE. A novel approach is exploited, introducing, for the first time, the concept of effective energy in the study of strangeness production in hadronic collisions at the LHC. In this work, the ALICE Zero Degree Calorimeters are used to measure the energy carried by forward emitted baryons in pp collisions, which reduces the effective energy available for particle production with respect to the nominal centre-of-mass energy. The results presented in this thesis provide new insights into the interplay, for strangeness production, between the initial stages of the collision and the produced final hadronic state. Finally, the first Run 3 results on the production of $\Omega^{\pm}$ ($\bar{\Omega}^{+}$) multi-strange baryons are presented, measured in pp collisions at $\sqrt{s}$ = 13.6 TeV and 900 GeV, the highest and lowest collision energies reached so far at the LHC. This thesis also presents the development and validation of the ALICE Time-Of-Flight (TOF) data quality monitoring system for LHC Run 3. This work was fundamental to assess the performance of the TOF detector during the commissioning phase, in the Long Shutdown 2, and during the data taking period.