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Development of JADE, a new software for the verification and validation of nuclear data libraries
Get PDFNuclear cross sections are the pillars onto which the transport simulation of particles and radiations is built on. Since the nuclear data libraries production chain is extremely complex and made of different steps, it is mandatory to foresee stringent verification and validation procedures to be applied to it. The work here presented has been focused on the development of a new python based software called JADE, whose objective is to give a significant help in increasing the level of automation and standardization of these procedures in order to reduce the time passing between new libraries releases and, at the same time, increasing their quality.
After an introduction to nuclear fusion (which is the field where the majority of the V\&V action was concentrated for the time being) and to the simulation of particles and radiations transport, the motivations leading to JADE development are discussed. Subsequently, the code general architecture and the implemented benchmarks (both experimental and computational) are described. After that, the results coming from the major application of JADE during the research years are presented. At last, after a final discussion on the objective reached by JADE, the possible brief, mid and long time developments for the project are discussed.Le sezioni d'urto nucleari sono alla base della simulazione del trasporto di particelle e radiazioni. Poichè la catena produzione di librerie di dati nucleari è estremamente complessa e si compone di diversi passaggi, è opportuno prevedere stringenti procedure di verifica e validazione. Il lavoro di tesi qui presentato si è concentrato sullo sviluppo in python di un nuovo software, JADE, il cui obbiettivo è quello di aiutare significativemente nella automatizzazione e standardizzazione di queste procedure in modo tale da diminuire il tempo necessario per il rilascio di nuove versioni di queste librerie e allo stesso tempo aumentarne la qualità.
Dopo un' introduzione alla fusione nucleare (ambito sul quale si è concentrata per il momento l'attività di V\&V) e alla simulazione del trasporto di particelle e radiazioni, vengono discusse le motivazioni che hanno portato allo sviluppo di JADE. Successivamente, sono descritti l'architettura generale del codice ed i benchmark, sia sperimentali che computazionali, che sono stati implementati. Inoltre, vengono riportati i risultati ottenuti dalle principali applicazioni di JADE effettuate durante gli anni di ricerca. Infine, dopo un ultima discussione conclusiva sugli obbiettivi raggiunti da JADE, vengono esaminati i possibili sviluppi a breve, medio e lungo periodo per il progetto
Pathophysiology of bile acid aspiration in lung transplant recipients
Get PDFDuodeno-gastroesophageal reflux aspiration is associated with chronic lung allograft dysfunction (CLAD) and aspiration of bile acids (BA), functional molecules in the gastro-intestinal tract with emulsifying properties. While links between reflux aspiration to lung disease have been identified, the relevance of bile acid as molecular ligands and outcome predictors is poorly defined. We sought to determine and quantify the various BA species in airways of the lung transplant recipients to better understand the various effects of aspirated BA that contribute to post-transplantation outcomes and to investigate their molecular effects on airway function and contractility
Architectures and circuits for ultra-low-power integrated wake-up radios
Get PDFA Wake-Up Radio (WuRX) is an enabling technology for the Internet-of-Things. It i is composed of two subsystems: the Analog Front-End (AFE) and the Baseband Logic (BBL). AFE task is to turn the input OOK-modulated signal into a stream of bits. WuRX AFEs can be classified in clocked or clockless. Clocked AFEs leverage the use of an always-on clock, which inevitably implies a dramatic increase in power consumption, while clocked AFEs do not. Therefore, this thesis focuses on ultra-low-power WuRXs featuring clockless AFEs. The Baseband Logic (BBL) compares the received bitstream with the address of the specific node and, if the two match, issues a Wake-Up interrupt. In particular, the packet containing the address of the node is called Wake-Up Packet (WUP). WuRX performances are conventionally evaluated on two metrics: Missed Detection Rate (MDR) and False Alarm Rate (FAR). The first quantifies its detection capability while the second the frequency of false wake-ups due to noise or interferers. While AFE can detect infinite bits, baseband logic architectures, due to the phase/frequency mismatch between received data and clock, can process WUPs of limited length (8 up to 63 bits). Such lengths turn out to be not acceptable in case the WuRX must tolerate very low FARs or receive more sophisticated and encrypted WUPs. In particular, the latter is a key feature to enhance the security of WSANs in private or sensitive data-processing applications. To overcome the issues related to the maximum WUP length, this thesis proposes a nanowatt Gated Oscillator Clock and Data Recovery (GO-CDR) circuit which enables the WuRX to receive hundreds of bits.
Another key-feature proposed in this thesis involves the generation of the threshold voltage for the continuous time comparator within the clockless AFE
Regulating FinTech: The perspectives of law, economics, and technology
Get PDFFinTech (financial technology, ‘‘FinTech’’) is a double-edged sword as it brings both benefits and risks. This study appraised FinTech’s technological nature that brings changes in complexity in modern financial markets to identify the information deficits and its undesirable outcomes. Besides, as FinTech is still developing, the information regarding, for instance, whether and how to apply regulation may be insufficient for both regulators and those regulated. More one-size-fits-all regulation might accordingly be adopted, thereby resulting in the adverse selection. Through the lens of both law and economics and law and technology, this study suggested AFR (adaptive financial regulation, ‘‘AFR’’) of FinTech to solve the underlying pacing issue. AFR is dynamic, enabling regulatory adjustments and learning. Exploring and collecting information through experiments and learning from experiments are the core of AFR. FinTech regulatory sandboxes epitomize AFR. This study chose Taiwan as a case study. This study found several barriers to adaptive and effective FinTech regulation. Unduly emphasizing consumer protection and the innovation entry criterion by improperly imposing limits on the entry into sandboxes, ignoring post-sandbox mechanisms, and relying on detailed, specific and prescriptive rules to formulate sandboxes are examples. To solve these barriers, this study proposed several solutions by looking into the experiences in other jurisdictions and analyzing. First, striking a balance between encouraging innovation and ensuring financial stability and consumer protection is indispensable. Second, entry to sandboxes should be facilitated by improving the selection criteria. Third, adhering to realizing regulatory adjustment and learning to adapt regulation to technology, this study argued that systematic post-sandbox mechanisms should be established. Fourth, this study recommended “more principles-based sandboxes”. Principles rather than rules should be the base on which sandboxes or FinTech regulation are established. Having principles could provide more flexibility, being easier to adjust and adapt, and better at avoiding
Understanding molecular mechanisms of resistance to immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC)
Get PDFImmune checkpoint inhibitors (ICI) that target PD-1/PD-L1 have recently emerged as an integral component of front-line treatment in metastatic NSCLC patients. The PD-1 inhibitor pembrolizumab is approved as monotherapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) of ≥1% and in combination with platinum doublet chemotherapy regardless of PD-L1 expression level. However, responses to either regimen occur in only a minority of cases, and PD-L1 TPS is limited as a biomarker in predicting whether a cancer will respond to PD-1 inhibition alone or would be more likely to benefit from PD-1 inhibition plus chemotherapy. Additional biomarkers of immunotherapy efficacy, such as tumor mutational burden (TMB), have not been incorporated into routine clinical practice for treatment selection. The identification of patients who have the greatest likelihood of responding to immunotherapies is critical for guiding treatment decisions. IN addition, early indicators of response could theoretically prevent patients from staying on an ineffective therapy where they might experience complications due to disease progression or develop toxicities from unnecessary exposure to an inactive agent. The aim of this research project is to investigate the clinicopathologic and molecular determinant of response/resistance to the currently available immune checkpoint inhibitors, in order to identify therapeutic vulnerabilities that can be exploited to improve the clinical outcomes of patients with advanced NSCLC
Enhancing predictive capability of models for solubility and permeability in polymers and composites
Get PDFThe interpretation of phase equilibrium and mass transport phenomena in gas/solvent - polymer system at molten or glassy state is relevant in many industrial applications. Among tools available for the prediction of thermodynamics properties in these systems, at molten/rubbery state, is the group contribution lattice-fluid equation of state (GCLF-EoS), developed by Lee and Danner and ultimately based on Panayiotou and Vera LF theory. On the other side, a thermodynamic approach namely non-equilibrium lattice-fluid (NELF) was proposed by Doghieri and Sarti to consistently extend the description of thermodynamic properties of solute polymer systems obtained through a suitable equilibrium model to the case of non-equilibrium conditions below the glass transition temperature. The first objective of this work is to investigate the phase behaviour in solvent/polymer at glassy state by using NELF model and to develop a predictive tool for gas or vapor solubility that could be applied in several different applications: membrane gas separation, barrier materials for food packaging, polymer-based gas sensors and drug delivery devices. Within the efforts to develop a predictive tool of this kind, a revision of the group contribution method developed by High and Danner for the application of LF model by Panayiotou and Vera is considered, with reference to possible alternatives for the mixing rule for characteristic interaction energy between segments. The work also devotes efforts to the analysis of gas permeability in polymer composite materials as formed by a polymer matrix in which domains are dispersed of a second phase and attention is focused on relation for deviation from Maxwell law as function of arrangement, shape of dispersed domains and loading
Evaluation of clinical implications correlate to genetic polymorphisms and pharmacokinetic of transdermal fentanyl
Get PDFABSTRACT
Background:Strong opioids are the treatment of choice for moderate to severe cancer-related pain. Fentanyl is a synthetic opioid with high affinity for the μ-opioid receptor and is 75–100 times more potent than morphine.
Fentanyl is metabolised rapidly, particularly in the liver and only 10% is excreted as intact substance.
The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way.
The influence of BMI and gender on fentanyl pharmacokinetics is questionable. Pharmacogenetic, may influence fentanyl pharmacokinetic and other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetic.
Method: This is a biological interventional prospective, single-center study in 49 patients with solid or haematological neoplasm treated with transdermal fentanyl undergoing 5-step pharmacokinetic and pharmacogenetic withdrawals from administration of the fentanyl patch.
Objective:to evaluate the pharmacokinetic and pharmacogenetic of transdermal fentanyl in relation to the patient's clinical response on pain
Results: Sex was the only parameter with evidence of different distribution between responders and non-responders , showing a major chance for male to be responders than females.
We found some correlation with pharmacokinetic parameters and sex, regarding adverse events and NRS correlation with BPI.
NAT2 and UGT2B7 polymorphisms are associated with AUC and Cmax kinetics parameters, NAT2 and CYP4F2 showed some evidence of association with the fentanyl dosage and CYP2B6 polymorphism seemed to be correlate with side effects.
Conclusion:
Small sample size of study population make difficult do find some significant correlation between pharmacogenetic, pharmacokinetic and clinical response.
Larger studies are needed to increase knowledge about response to opioid treatment in cancer patients to better individualized pain treatment.ABSTRACT
Background:Strong opioids are the treatment of choice for moderate to severe cancer-related pain. Fentanyl is a synthetic opioid with high affinity for the μ-opioid receptor and is 75–100 times more potent than morphine.
Fentanyl is metabolised rapidly, particularly in the liver and only 10% is excreted as intact substance.
The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way.
The influence of BMI and gender on fentanyl pharmacokinetics is questionable. Pharmacogenetic, may influence fentanyl pharmacokinetic and other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetic.
Method: This is a biological interventional prospective, single-center study in 49 patients with solid or haematological neoplasm treated with transdermal fentanyl undergoing 5-step pharmacokinetic and pharmacogenetic withdrawals from administration of the fentanyl patch.
Objective:to evaluate the pharmacokinetic and pharmacogenetic of transdermal fentanyl in relation to the patient's clinical response on pain
Results: Sex was the only parameter with evidence of different distribution between responders and non-responders , showing a major chance for male to be responders than females.
We found some correlation with pharmacokinetic parameters and sex, regarding adverse events and NRS correlation with BPI.
NAT2 and UGT2B7 polymorphisms are associated with AUC and Cmax kinetics parameters, NAT2 and CYP4F2 showed some evidence of association with the fentanyl dosage and CYP2B6 polymorphism seemed to be correlate with side effects.
Conclusion:
Small sample size of study population make difficult do find some significant correlation between pharmacogenetic, pharmacokinetic and clinical response.
Larger studies are needed to increase knowledge about response to opioid treatment in cancer patients to better individualized pain treatment
The Maastricht paradox. The different economic and political models for the inclusive future of the EU
Get PDFLa crisis existencial del proyecto de integración europea constituye el principal reto al que debe enfrentarse la Comunidad en su futuro más inmediato puesto que se alza como toda una amenaza para la continuidad del sistema establecido desde el Tratado fundacional de Roma (1957). Las tres crisis acontecidas durante los primeros años del siglo XXI, véase la gran crisis económica del año 2008, la pandemia global de la Covid-19 y la actual intervención de la Federación Rusa en Ucrania, están poniendo constantemente a prueba la firmeza de los cimientos y valores sobre los cuales se ha construido la Comunidad durante todos estos años.
Esta tesis doctoral pretende ser una contribución académica al debate abierto en las sociedades comunitarias acerca de por donde debe de transitar la evolución del proyecto de integración europea en los próximos años. Para conseguir alcanzar este objetivo, la investigación se retrotrae hasta los orígenes del proceso de integración y avanza en la línea temporal hasta nuestros días, analizando con ello las posibles causas que pudieran encontrarse detrás de la crisis existencial actual. A su vez, , la investigación estudia con detenimiento los múltiples efectos que está generando la problemática existencial en los Estados miembros en los últimos años, tales como el aumento del apoyo social a favor de actores considerados populistas o el fenómeno de la creciente desafección ciudadana.
Esta investigación analiza los distintos escenarios propuestos por la Comisión Europea en su Libro Blanco sobre el futuro de Europa para determinar cuál podría ser el mejor escenario que concordara con la nueva realidad económica y sociopolítica que actualmente impera en los Estados miembro. Lo que se persigue es formular una propuesta que pueda dar por terminada la crisis existencial de la Comunidad abriendo con ello una nueva etapa en la historia de la integración europea.The existential crisis of the European integration project constitutes the main challenge that the Community must face in its most immediate future, since it stands as a threat to the continuity of the system established since the founding Treaty of Rome (1957). The three crises that occurred during the first years of the 21st century, see the great economic crisis of 2008, the global pandemic of Covid-19 and the current intervention of the Russian Federation in Ukraine, are constantly testing the firmness of the foundations and values on which the Community has been built during all these years.
This doctoral thesis aims to be an academic contribution to the open debate in community societies about where the evolution of the European integration project should go in the coming years. In order to achieve this objective, the investigation goes back to the origins of the integration process and advances in the time line to the present day, thereby analyzing the possible causes that could be found behind the current existential crisis. In turn, later, the research carefully studies the multiple effects that existential problems are generating in the Member States in recent years, such as the increase in social support in favor of actors considered populists or the phenomenon of growing citizen disaffection. .
Finally, this research analyzes in detail the different scenarios proposed by the European Commission in its White Paper on the future of Europe to determine which could be the best scenario that would match the new economic and sociopolitical reality that currently prevails in the Member States. . With this, what is sought is to formulate a proposal that can end the existential crisis of the Community, thus opening a new stage in the history of European integration
Deploying and processing neural representations of signals
Get PDFNeural representations (NR) have emerged in the last few years as a powerful tool to represent signals from several domains, such as images, 3D shapes, or audio. Indeed, deep neural networks have been shown capable of approximating continuous functions that describe a given signal with theoretical infinite resolution. This finding allows obtaining representations whose memory footprint is fixed and decoupled from the resolution at which the underlying signal can be sampled, something that is not possible with traditional discrete representations, e.g., grids of pixels for images or voxels for 3D shapes. During the last two years, many techniques have been proposed to improve the capability of NR to approximate high-frequency details and to make the optimization procedures required to obtain NR less demanding both in terms of time and data requirements, motivating many researchers to deploy NR as the main form of data representation for complex pipelines. Following this line of research, we first show that NR can approximate precisely Unsigned Distance Functions, providing an effective way to represent garments that feature open 3D surfaces and unknown topology. Then, we present a pipeline to obtain in a few minutes a compact Neural Twin® for a given object, by exploiting the recent advances in modeling neural radiance fields. Furthermore, we move a step in the direction of adopting NR as a standalone representation, by considering the possibility of performing downstream tasks by processing directly the NR weights. We first show that deep neural networks can be compressed into compact latent codes. Then, we show how this technique can be exploited to perform deep learning on implicit neural representations (INR) of 3D shapes, by only looking at the weights of the networks
Sviluppo di nuovi cross-linker per la stabilizzazione del legame adesivo
Get PDFAims: This thesis aimed to investigate the influence of different collagen cross-linkers, as separate primers or contained within desensitizing agents, on the longevity of dental restorations and on the dentinal enzymatic activity immediately, or after aging in vitro. Methods: A series of studies was conducted using several different cross-linking molecules and several adhesive systems. Four studies investigated the longevity of the hybrid layer by means of microtensile bond strength test, and the enzymatic activity using gelatin and in situ zymography, immediately or after 1 year of aging in the artificial saliva. The first study tested samples bonded with or without a cross-linking agent, that were previously aged for 5 years. The degradation of the hybrid layer was observed using transmission electron microscopy, the enzymatic activity in the hybrid layer using in situ zymography. Raman spectroscopy was used to investigate whether the active substance was still within the hybrid layer after 5 years. Results: The results of the studies showed that collagen cross-linkers were efficient in preserving bond strength after aging in vitro when used as separate primers on demineralized or partially demineralized dentin. In the cases when the cross-linker was utilized on mineralized dentin, bond strength results were higher than in the control groups immediately and after aging, however, no difference in enzymatic activity was detected after aging. Conclusions: The tested cross-linker molecules used as separate primers in etch-and-rinse and self-etch adhesives seem to be clinically applicable, since the procedure is not overly time-consuming and seems to preserve the hybrid layer over time. As for the cross-linkers contained in the desensitizing agent, when utilized before the adhesive procedures, it has shown to increase the bond strength of self-etch adhesives, but further studies are needed to better understand its effect on the enzymatic activity and crosslinking effects on mineralized dentin