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Measurement techniques for the characterization of radio frequency gallium nitride devices and power amplifiers
Get PDFThe rapid growth of mobile telecommunications has fueled the development of the fifth generation (5G) of standards, aiming to achieve high data rates and low latency. These capabilities make use of new regions of spectrum, wider bandwidths and spectrally efficient modulations. The deployment of 5G relies on the development of radio-frequency (RF) technology with increased performance. The broadband operation at high-power and high-frequency conditions is particularly challenging for power amplifiers (PA) in transmission stages, which seek to concurrently maximize linearity and energy efficiency.
The properties of Gallium Nitride (GaN) allow the realization of active devices with favorable characteristics in these applications. However, GaN high-electron mobility transistors (HEMTs) suffer from spurious effects such as trapping due to physical defects introduced during the HEMT growth process. Traps dynamically capture and release mobile charges depending on the applied voltages and temperature, negatively affecting the RF PA performance.
This work focuses on the development of novel measurement techniques and setups to investigate trapping behavior of GaN HEMTs and PAs. At low-frequency (LF), charge dynamics is analyzed using pulsed current transient characterizations, identifying relevant time constants in state-of-the-art GaN technologies for 5G. Instead, at high-frequency, tailored methods and setups are used in order to measure trapping effects during the operation of HEMTs and PAs in RF modulated conditions. These RF characterizations emulate application-like regimes, possibly involving the control of the device’s output load termination. Therefore, an innovative wideband active load pull (WALP) setup is developed, using the acquisition capabilities of standard vector-network-analyzers. Moreover, the implications of performing error-vector-magnitude characterizations under wideband load pull conditions are studied. Finally, an efficient implementation of a modified-Volterra model for RF PAs is presented, making use of a custom vector-fitting algorithm to simplify the nonlinear memory operators and enable their realization in simulation environments
Biological analysis of the in-vitro effects of homologous recombination inhibition and its use in cancer treatment through synthetic lethality
Get PDFSynthetic lethality represents an anticancer strategy that targets tumor specific gene defects. One of the most studied application is the use of PARP inhibitors (e.g. olaparib) in BRCA1/2-less cancer cells. In BRCA2-defective tumors, olaparib (OLA) inhibits DNA single-strand break repair, while BRCA2 mutations hamper homologous recombination (HR) repair. The simultaneous impairment of those pathways leads BRCA-less cells to death by synthetic lethality.
The projects described in this thesis were aimed at extending the use of OLA in cancer cells that do not carry a mutation in BRCA2 by combining this drug with compounds that could mimic a BRCA-less environment via HR inhibition.
We demonstrated the effectiveness of our “fully small-molecule induced synthetic lethality” by using two different approaches.
In the direct approach (Project A), we identified a series of neo-synthesized compounds (named RAD51-BRCA2 disruptors) that mimic BRCA2 mutations by disrupting the RAD51-BRCA2 interaction and thus the HR pathway. Compound ARN 24089 inhibited HR in human pancreatic adenocarcinoma cell line and triggered synthetic lethality by synergizing with OLA. Interestingly, the observed synthetic lethality was triggered by tackling two biochemically different mechanisms: enzyme inhibition (PARP) and protein-protein disruption (RAD51-BRCA2).
In the indirect approach (Project B), we inhibited HR by interfering with the cellular metabolism through inhibition of LDH activity. The obtained data suggest an LDH-mediated control on HR that can be exerted by regulating either the energy supply needed to this repair mechanism or the expression level of genes involved in DNA repair. LDH inhibition also succeeded in increasing the efficiency of OLA in BRCA-proficient cell lines. Although preliminary, these results highlight a complex relationship between metabolic reactions and the control of DNA integrity.
Both the described projects proved that our “fully small-molecule-induced synthetic lethality” approach could be an innovative approach to unmet oncological needs
Design and synthesis of RAD51-BRCA2 disruptors that trigger synthetic lethality in pancreatic cancer in combination with Olaparib
Get PDFMy PhD research project has been finalized to the discovery of potential RAD51-BRCA2 protein-protein interaction (PPI) disruptors, able to trigger synthetic lethality (SL) in pancreatic cancer in combination with PARP inhibitor Olaparib. SL has been validated clinically, as anticancer therapeutic strategy, through the efficacy of Olaparib in BRCA2-defective cancers. In this context, we proposed to trigger a fully small-molecule-induced SL, combining RAD51-BRCA2 PPI disruptor with Olaparib to target pancreatic cancer. RAD51-BRCA2 PPI is essential in homologous recombination (HR) for DNA repair and it is mediated by two critical “hotspots” on RAD51 surface, Zone I and Zone II, suitable sites to design small molecule disruptors.
This thesis reports the application of two distinct hit identification strategies to identify potential RAD51-BRCA2 PPI disruptors.
In the first part of this project, an approach of structure-based design was applied, which exploited Virtual Screening (VS) campaign as hit identification strategy, followed by chemical modifications and SAR studies. Two VS, targeting separately Zone I and Zone II, led to the discovery of two classes of potential RAD51-BRCA2 PPI disruptors. In particular, VS targeting Zone II identified the dihydroquinolone pyrazoline 19 as hit compound. The optimization of a general synthetic strategy gave access to a series of analogs for SAR investigation, leading to compound 47 with the desired biological profile. Indeed, 47 inhibited RAD51-BRCA2 PPI, reduced cell HR and triggered cell death in combination with Olaparib in BxPC-3 cells, fully reproducing the paradigm of SL.
The second part of this thesis was devoted to a second hit identification strategy. During the six-month placement at HIPS in Prof. A. K. H. Hirsch’s group, I applied a technique of target directed dynamic combinatorial chemistry (tdDCC) on RAD51. This approach allowed the identification of N-acylhydrazone-based compounds, which proved to inhibit RAD51-BRCA2 PPI at micromolar range in the preliminary biochemical assay
Novel membranes for hemodialysis application
Get PDFThe present work is focused on the synthesis and characterization of novel materials for hemodialysis applications. Cellulose acetate was chosen as base polymer for the preparation of porous Mixed Matrix Membrane adsorbers (MMMAs) and for the synthesis of hybrid ultrafiltration membranes. Hemodialysis is a renal replacement therapy used to eliminate,the waste products and excess fluids accumulating in the blood of people affected by an end stage renal disease. The main environmental drawback associated to it is the large water consumption. The MMMAs were prepared with the porpoise of eliminating waste metabolites (uremic toxins) from the spent dialysate solution, with the prospective limiting the consumption of water related to the process. Batch tests of MMMAs showed that the removal of uric acid is almost complete while the one of urea and creatinine is limited to a 20/30 %. The thinking behind the concept of MMMAs was aimed to develop a small a lab scale chromatographic cartridge to continuously remove uremic toxins from an aqueous feed solution. The cartridge was packed with MMMAs and tested with a mixture of toxins. Experiments results shown a promising removal capability of the system even if the necessity of a higher surface area to achieve better efficiency is denoted.
The other important issue related to hemodialysis is the assessment of an overall mass transfer rates in hemodialyzers. The mass transfer correlations proposed in literature do not take into account the effect of permeation and are developed for turbulent flow regime. Therefore, hybrid cellulose acetate/Silica ultrafiltration membranes were prepared to characterize a surrogate system of an artificial kidney (AK) in terms of fluid mechanics and mass transfer. The effect of surface roughness and suction on the velocity profiles was determined and a new dimensionless mass transfer correlation accounting for permeation was developed
Scheduling of Resources in Renewable Energy Communities
Get PDFThis work presents a detailed study of the scheduling of power and energy resources in renewable energy communities (RECs). The study has been developed starting from the analysis of a single basic unit of the community, i.e., the prosumer and its microgrid, to the scheduling and expansion of the energy community concept with several prosumers through several scenarios.
The individual scheduling problem of the prosumer has been studied as a day-ahead deterministic problem and as a multistage stochastic problem to consider uncertainties associated with energy generation and energy consumption. Furthermore, an approach has been formulated to consider the integration of bidirectional charging services of electrical vehicles within a local energy system with the presence of renewable generation.
Moreover, this thesis focuses on the scenario in which direct energy transactions between prosumers located within a REC are allowed in addition to the energy transactions with the external energy provider. The day-ahead scheduling problem has been addressed by a centralized approach and by a distributed approach based on the alternating direction method of multipliers (ADMM). The developed approaches provide the scheduling of the available energy resources to limit the balancing action of the external grid and allocate the internal network losses to the corresponding energy transactions.
Finally, the thesis presents a coordinated day-ahead and intra-day approach to provide the optimal scheduling of the resources in a REC. In this case, the ADMM-based procedure, which is aimed at minimizing the total energy procurement costs, is adapted to cope with the impact of the fluctuation of both the local energy generation and demand during the day. To achieve this, a day-ahead multistage stochastic optimization approach is combined with an intra-day decision-making procedure, able to adjust the scheduling of the energy resources according to the current operational conditions
The Exploration of Chu Capitals
Get PDFSearching for capitals of the pre-Qin period has always been a primary goal of modern Chinese archaeology. As once the vassal state with the largest territory in the Zhou era, the Chu has constantly been the center of this topic. How did Chu capitals change during the more than eight hundred years from the state’s founding to its demise, has triggered various hypotheses and discussions among the scholars. Taking time as the central axis and being problem-oriented, this thesis explores the Chu capitals from a long-term perspective. The work mainly includes the textual research analysis of the capital’s geographic location, the study of the era and nature of the urban sites designated (or inferred) as the capital, and the detailed discussion of its spatial layout. Besides, this thesis reflected on the theoretical approaches that Chinese archaeologists used for reconstructing early dynastic history, and then proposed future improvements
Advanced Functional Organic-Inorganic Hybrid (Nano)Materials: from Theranostics to Organic Electronics and Additive Manufacturing
Get PDFThis work is going to show the activities performed in the frame of my PhD studies at the University of Bologna, under the supervision of Prof. Mauro Comes Franchini, at the Department of Industrial Chemistry “Toso Montanari”. The main topic of this dissertation will be the study of organic-inorganic hybrid nanostructures and materials for advanced applications in different fields of materials technology and development such as theranostics, organic electronics and additive manufacturing, also known as 3D printing.
This work is therefore divided into three chapters, that recall the fundamentals of each subject and to recap the state-of-the-art of scientific research around each topic. In each chapter, the published works and preliminary results obtained during my PhD career will be discussed in detail
Defective design in defective products legislation
Get PDFAunque ni la Directiva 85/374/CEE relativa a la aproximación de las disposiciones legales, reglamentarias y administrativas de los Estados Miembros en materia de responsabilidad por los daños causados por productos defectuosos, ni el Real Decreto Legislativo 1/2007, de 16 de noviembre, por el que se aprueba el texto refundido de la Ley General para la Defensa de los Consumidores y Usuarios y otras leyes complementarias, que recoge dicha directiva en la actualidad en el sistema español, ni el d.p.r. 24 maggio 1988, nº 224, posteriormente introducido en el d. lgs 6 settembre 2005, nº 206, que hace lo mismo en el sistema italiano, establecen diferencias entre los distintos tipos de defectos que convierten a un producto en «defectuoso», la doctrina ha seguido diferenciando entre defectos de fabricación, defectos de información y defectos de diseño. La presente tesis intenta comprobar si tal clasificación es meramente académica, o si por el contrario, el que el defecto sea de un tipo o sea de otro implicará alguna especialidad en su tratamiento jurídico, y ello lo hace centrándose en los defectos de diseño, que han dado lugar a unos importantes desarrollos en la jurisprudencia norteamericana, y que. parecen estar asociados a los llamados «riesgos de desarrollo». Para ello se analiza la más reciente jurisprudencia norteamericana, italiana y española.Although neither the Council directive 85/374/EEC related to the approximation of the legal, regulatory and administrative provisions of the Member States, regarding liability caused by defective products, nor the (Spanish) Royal Legislative Decree 1/2007, of November 16th, approving the consolidated draft/text of the General Law for the Defence of Consumers and Users, together with other complementary laws, which currently implements the directive mentioned before in the Spanish system, nor the presidential decree 24 may 1988, nº 224, hereinafter introduced in the legislative decree 6 september 2005, nº 206, which does the same in the Italian system, establish differences between the different kind of defects that make a product «defective», the doctrine has continued making difference between manufacturing defects, information defects and defects of design. This thesis tries to verify if that classification is merely academic, or if on the contrary, the fact that the defect is of one type or another will imply some speciality in its legal treatment, and this is made focusing in the defects of design, which have led to some important developments in North American jurisprudence, that seem to be associated with the so-called «development risks». With that purpose, the most recent North American, Italian and Spanish jurisprudence is analysed.Sebbene né la Direttiva 85/374/CEE, relativa al ravvicinamento delle disposizioni legislative, regolamentari e amministrative degli Stati membri in materia di responsabilità da prodotti difettosi, né il Regio Decreto Legislativo 1/2007, del 16 novembre, che approva il testo rivisto della Legge Generale per la Difesa dei Consumatori e degli Utenti e altre leggi complementari, che attualmente include detta direttiva nel sistema spagnolo tale direttiva nel sistema spagnolo, né il D.P.R. 24 maggio 1988, n. 224, successivamente abrogato e sostituito dal D.Lgs. 6 settembre 2005, n. 206, di attuazione della citata direttiva nel sistema italiano, stabiliscano differenze tra i diversi tipi di difetti che rendono un prodotto «difettoso», la dottrina ha continuato a distinguere tra difetto di fabbricazione, difetto di informazione e difetto di progettazione. La presente tesi tenta di verificare se tale classificazione sia meramente accademica o se, al contrario, che il difetto, di un tipo o altro, comporti una certa specialità nel suo trattamento giuridico, e lo fa concentrandosi sul difetto di progettazione, il quale ha dato origine ad alcuni importanti sviluppi all’interno della giurisprudenza nordamericana e che sembrano essere associati al cosiddetto «rischio da sviluppo». A tal fine, si analizza la più recente giurisprudenza nordamericana, italiana e spagnola
Innovative techniques for the hydraulic and hydrological variables assessment
Get PDFThis Thesis focues on two main research topics: (1) the use of innovative techniques for the evaluation of main hydraulic variables of natural rivers (e.g. river bathymetry, discharge, water level) and (2) the monitoring and hydrological modelling of Monate Lake (Varese, Italy)
Development and chemo-mechanical characterization of eco-compatible extenders containing REOB and recycled tyres’ rubber for the production of greener bituminous binders
Get PDFThe concepts of circular economy and sustainability are the basis of the present experimental research that seeks to reduce the environmental impact of traditional road construction materials. This study mainly focuses on the development and the chemo-mechanical characterization of bitumen extenders containing rubber (R) from end-of-life tyres (ELTs) and re-refined engine oil bottoms (REOBs) for the production of innovative and eco-friendly extended bitumens (i.e. bituminous binders containing 25%wt. of recycled products) and asphalt mixtures. In order to create more sustainable asphalt mixes, also recycled aggregates are used for partial replacement of virgin natural aggregates in the aggregate skeleton. The experimental program encompassed five successive steps: (i) the evaluation of physicochemical properties of R and REOB, (ii) the definition of the optimal extenders by the development of a new protocol and their characterizations, (iii) the realization and investigation of the chemo-rheological responses of the extended bitumens at different boundary conditions, (iv) the assessment of the effectiveness of analytical method to predict the rheological parameters of extended bitumens and, finally, (v) the analysis of the mechanical performances of the corresponding asphalt mixtures. A standard 50/70 penetration grade bitumen was chosen as a reference material and the main constituent of the innovative bituminous products. The results of this study underlined the importance of material characterization. The incorporation of R-REOB extenders strongly affects the chemo-rheological responses of the resulting extended bitumens and asphalt mixtures overall the boundary conditions. While the presence of R and the consequent formation of a polymer network improves the elasticity of the final products, especially at high test temperatures; the addition of REOB, softens the bituminous binders and asphalt mixes increasing their response at low test temperatures. Nonetheless, the use of recycled products increased the susceptibility of bituminous material under damaging conditions, which would need further investigations