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Physical Layer Identification and authentication of electronic devices
No full textIn this thesis, I have investigated the problem of identification and authentication of electronic devices through their physical layer intrinsic features or fingerprints. The concept is that small differences in the electronic components of electronic devices leave small but significant traces in the digital output generated by the electronic device. Then, an analysis of the digital output provides the capability to identify and/or authenticate an electronic device from its digital output with a degree of accuracy, which is based on various factors including environmental effects. This research area has become more prominent in recent times due to the increasing computing power available for signal processing and analysis, which allows a more efficient and accurate extraction of the fingerprints. Even if there is considerable research in this area, which has proven the concept both with theoretical analysis and experimental results, there are still many aspects to be investigated both for the different types of electronic devices and for the analysis of the digital output through signal processing and machine learning techniques. The PhD activities have investigated various novel aspects in comparison to the existing literature. This thesis describes most of the results and describes the novelty in comparison to previous research literature. Three specific use cases were considered: identification of wireless devices, microphones and magnetometers
Genomic molecular markers to monitor minimal residual disease with a non invasive liquid biopsy in breast cancer patients
No full textBackground
Circulating cell free DNA (cfDNA) is one of the most intriguing and developing topic in the field of precision and personalized medicine.
From 1977, when Leon and colleagues reported an increase in cfDNA in cancer patients, several studies have tried to explain and understand deeper how cfDNA is produced, lasts into the bloodstream, and what kind of information it contains and can be useful to detect and/or manage the disease.
Liquid biopsy has already been approved to determine those patients that will benefit from an epidermal growth factor receptor (EGFR)-targeted therapy in non-small cell lung cancer (NSCLC).
Nowadays, several studies on clinical applicability and clinical trials are on-going, in order to determine if information obtained from cfDNA can drive clinical decisions.
Homologous recombination (HR) is a high-fidelity DNA repair mechanism involved in double-strand DNA (dsDNA) break repair. Recent studies have highlighted a broader involvement of HR status in BRCA wild type breast cancers (BC), in particular in triple negative BC (TNBC).
Identification of mutations in the HR pathway can suggest the administration of a specific therapy, such as platinum agents or PARP inhibitors (PARPi).
Material & Methods
In this work we have collected fresh tissue and blood from 6 BC patients.
Plasma was separated with two consecutive centrifugations to completely remove cell and cellular debris.
We have extracted genomic DNA (gDNA) from fresh tissue and cfDNA from plasma using commercial kits.
We have analysed in parallel both DNAs with the Homologous Recombination Solution™ kit (Sophia™ Genetics) that allows the identification of mutations in exonic regions of 16 genes involved in HR.
Results
All samples passed target enrichment and sequencing quality controls (QC).
In 3 out of 6 patients no mutations were detected in both gDNA and cfDNA. Patients 1 and 6 had mutations in gDNA not detected in cfDNA. Patient 2 had 2 mutations in gDNA and only one of the two was detected in cfDNA.
Conclusions
This kit can be used to analyse cfDNA, as confirmed by QC reports.
Interestingly, the identification of the mutation in TP53 in patient 2’s cfDNA supports the possibility to detect mutations with this kit. The higher variant fraction (VF) in cfDNA compared to gDNA can sustain the possibility to have a broader detection of heterogeneity.
The non-recognition of mutations in cfDNA in patients carrying gDNA mutations can be ascribed to the reduced amount of cfDNA analysed and to the fact that tumoral DNA is only a fraction of the total cfDNA. Thus, the sample analysed can be unrepresentative of the circulating DNA pool.
The analysis of a higher number of samples will give us a clearer idea of the applicability of this kit to monitor HR mutational status in cfDNA of BC patients, giving us statistical significance of detection
Proteomics and network analysis identify common and specific pathways of neurodegeneration
No full textNeurodegenerative disorders, such as Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are multi-factorial in nature, involving several genetic mutations (in coding or regulatory regions) and epigenetic and environmental factors. The main clinical manifestation (movement disorders, cognitive impairment and/or psychiatric disturbances) depends on the neuron population being primarily affected. Complex and multifactorial neurodegenerative diseases can be investigated using a holistic approach that can give a global view about the pathogenetic process and shed light on specific and generic pathways of neurodegeneration. Proteomics offers a global molecular snapshot of proteins and consequently of processes that may influence neuronal death. The proteome in fact provides a dynamic view of what is happening in the system under investigation, because the expression of proteins, their abundance, their localization in tissues or cells, the type and amount of their post-translational changes depend from the environment and from the cellular physiological state. Therefore, all the projects presented in this thesis, by combining bioinformatics tools with proteomics, aimed at highlighting biochemical processes shared by different neurodegenerative diseases and diseasespecific pathways, which may justify the degeneration of dopaminergic neurons in PD. Finally, a focus on the mitochondrial interactome and proteome intended to elucidate important specific steps of the degenerative process in PD
CDKL5 and neuronal morphological defects: novel perspectives of microtubule related drugs
No full textMutations in the CDKL5 gene have been found in individuals with a rare neurodevelopmental disorder. CDKL5 is a serine/threonine kinase whose functions are still not fully understood. An aberrant neuronal morphology linked to Cdkl5 has been observed both in Cdkl5--‐silenced primary neurons as well as in Cdkl5--‐null brains strongly suggesting that these defects may underlie the cognitive impairment characterizing both patients and mice devoid of the kinase. The molecular basis of these defects is still far from understood but altered cytoskeletal dynamics are likely to be involved. The identification of IQGAP1 as novel CDKL5 interactor may provide a key to understand such neuronal defects. IQGAP1 promotes microtubule dynamics through its association with Rac1 and CLIP--‐170, whose activity on MTs might play a significant role in the regulation of cytoskeletal dynamics in cycling cells and neurons. Considering how the loss of CDKL5 negatively impacts on cellular and neuronal morphology, we envisaged that this kinase could regulate cytoskeletal dynamics acting directly or indirectly on CLIP--‐170. Indeed, CLIP--‐170 is known to regulate several aspects of neuronal morphology such as axon outgrowth, dendritic arborization and growth cone organization. By bridging the actin cytoskeleton to MTs, CLIP--‐170 coordinates proper cytoskeletal dynamics.
In the current study, we analysed the role of CDKL5 in the regulation of CLIP--‐170 activity. Through a FRET analysis on COS7 cells we demonstrated that the loss of CDKL5 causes CLIP--‐170 to be mainly in its closed inactive conformation, thus reducing its interaction with MTs. Furthermore, using Cdkl5--‐ KO primary hippocampal neurons we demonstrated that the loss of CDKL5 is detrimental for the correct progression of several steps of neuronal maturation. Moreover, we demonstrated that such defects can be restored upon treatment with pregnenolone (a neurosteroid which stabilizes the extended conformation of CLIP--‐170, increasing its affinity for MTs and promoting their polymerization) and Pregnenolone--‐Methyl--‐Ether, a synthetic non--‐metabolizable P5 derivative. We speculate that the positive effects of the two compounds are likely to be due to an activation of CLIP--‐ 170 functionality and a concomitant increase in MT dynamics
Robust optimization in data envelopment analysis: extended theory and applications.
No full textPerformance evaluation of decision-making units (DMUs) via the data envelopment analysis (DEA) is confronted with multi-conflicting objectives, complex alternatives and significant uncertainties. Visualizing the risk of uncertainties in the data used in the evaluation process is crucial to understanding the need for cutting edge solution techniques to organizational decisions. A greater management concern is to have techniques and practical models that can evaluate their operations and make decisions that are not only optimal but also consistent with the changing environment. Motivated by the myriad need to mitigate the risk of uncertainties in performance evaluations, this thesis focuses on finding robust and flexible evaluation strategies to the ranking and classification of DMUs. It studies performance measurement with the DEA tool and addresses the uncertainties in data via the robust optimization technique.
The thesis develops new models in robust data envelopment analysis with applications to management science, which are pursued in four research thrust. In the first thrust, a robust counterpart optimization with nonnegative decision variables is proposed which is then used to formulate new budget of uncertainty-based robust DEA models. The proposed model is shown to save the computational cost for robust optimization solutions to operations research problems involving only positive decision variables. The second research thrust studies the duality relations of models within the worst-case and best-case approach in the input – output orientation framework. A key contribution is the design of a classification scheme that utilizes the conservativeness and the risk preference of the decision maker. In the third thrust, a new robust DEA model based on ellipsoidal uncertainty sets is proposed which is further extended to the additive model and compared with imprecise additive models. The final thrust study the modelling techniques including goal programming, robust optimization and data envelopment to a transportation problem where the concern is on the efficiency of the transport network, uncertainties in the demand and supply of goods and a compromising solution to multiple conflicting objectives of the decision maker.
Several numerical examples and real-world applications are made to explore and demonstrate the applicability of the developed models and their essence to management decisions. Applications such as the robust evaluation of banking efficiency in Europe and in particular Germany and Italy are made. Considering the proposed models and their applications, efficiency analysis explored in this research will correspond to the practical framework of industrial and organizational decision making and will further advance the course of robust management decisions
Improving ecosystem exposure assessment of organic chemicals: evaluating their mobility and bioavailability with novel chemical measurements and modelling approaches.
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Existence, non existence and uniqueness results for higher order elliptic systems
No full textIn this dissertation, we deal with Hamiltonian Lane-Emden type systems where in place of the Laplace operator we take into account the polyharmonic operator. Recallthatthepolyharmonicoperatordoesnotalwayssatisfyamaximumprinciple. Indeed, if we take Dirichlet boundary conditions, the maximum principle is known to hold only on a ball or small deformations of a ball, whereas it fails on ellipses with sufficiently big ratio of half axes. On the one hand, if the operators in the two equations have the same order, the problem is variational. In this case, we prove some existence and non-existence results under Dirichlet boundary conditions on a sufficiently smooth bounded domain. We also consider more general nonlinearities than power-like. The existence result is achieved by means of a Linking Theorem on suitable fractional Sobolev spaces. On the other hand, if the operators have different orders the problem turns out to be non-variational: here we prove some existence results on a ball by means of a different approach, precisely we exploit degree theory and a blow-up analysis, combined with a suitably adapted moving planes technique and Liouville-type theorems. Moreover, we prove uniqueness of solutions to equations and systems up to order eight on a ball endowed with Dirichlet boundary conditions. The proof extends the classical argument by Gidas-Ni-Nirenberg
Scienze Umane e Medical Humanities nella didattica medica. Il contributo della Storia della Medicina
No full textLe scienze storiche si aggiornano continuamente rivedendo a volte anche totalmente i propri cardini interpretativi su cui si posano le loro fondamenta; anche la Storia della Medicina ha decisamente cambiato la propria attività di ricerca nel corso degli anni. Nello studio che ho condotto ho potuto constatare come nell’arco di un secolo gli indirizzi di ricerca storico-medica si siano diversificati, come sia mutato il panorama dei protagonisti, come siano sorti nuovi interessi per la storia delle istituzioni sanitarie, per la storia delle malattie e delle singole discipline specialistiche. Alla ricerca di date significative di questo percorso, credo sia stata davvero importante, come vedremo, la nascita nel 1907 della Società Italiana di Storia delle Scienze Mediche e Naturali. Questa ricerca si è posta gli obiettivi di delineare come, nell’arco del secolo scorso, siano cambiate le identità di quanti affrontavano lo studio della Storia della Medicina, di stendere le biografie dei protagonisti della Storia della Medicina, di ricostruire un secolo di storiografia italiana tramite gli autori ed i trattati, i maestri e le legislazioni, di trattare della nascita e dello sviluppo delle Società e della stampa periodica in Italia inerente la Storia della Medicina, di analizzare le attualità e le problematiche della attività didattico-formativa, di indicare quali prospettive la Storia della Medicina, le Scienze Umane e le Medical Humanities possano avere oggi nella formazione del medico. Da alcuni anni si è aperta una discussione sull’ingresso delle Scienze Umane e delle Medical Humanities nei percorsi formativi delle professioni mediche, in particolare nei piani didattici delle Scuole di Medicina. Con l’avanzare della ricerca medico-scientifica, abbiamo assistito alla spersonalizzazione del rapporto medico-paziente. La necessità di affrontare e gestire questi cambiamenti porta senza dubbio al recupero delle origini umanistiche della medicina anche attraverso corsi nel piano didattico degli studenti dell’area sanitaria. Qui entrano in campo le Scienze Umane e le Medical Humanities su cui negli ultimi anni abbiamo avuto un aumento crescente di studi e pubblicazioni non solo in Italia, segno di un costante aumento di interesse da parte degli studiosi. Per il raggiungimento degli obiettivi sopra esposti mi sono indirizzata verso quanto è stato pubblicato dalla Società Italiana di Storia della Medicina (SISM) attraverso il suo periodico ed attraverso i cinquantuno Congressi Nazionali, ho consultato i maggiori trattati di Storia della Medicina editi dall’inizio del secolo scorso, i documenti emanati dal Regno d’Italia, dal Consiglio Superiore di Sanità, dal Ministero della Salute e da quello dell’Istruzione oltre gli articoli in riviste. Ho consultato le fonti conservate presso biblioteche universitarie e documenti di collezioni private. Per la ricerca ergobiografica mi sono avvalsa di testimonianze di coloro che hanno conosciuto personalmente alcuni dei personaggi oggetti del mio studio oltre che di ricerca archivistica.
I risultati del mio studio hanno sottolineato l’importanza della Storia della Medicina nella storiografia italiana del secolo scorso e nei piani didattici formativi del personale sanitario, in particolar modo per gli studenti di medicina. Inoltre la mia ricerca vuole essere un punto di partenza per analizzare e riflettere sull’attualità, le problematiche e le prospettive dell’insegnamento di Storia della Medicina, anche nelle più vaste denominazioni di Scienze Umane e di Medical humanities, alla luce di una ridefinizione dei Settori Scientifico Disciplinari (SSD)
Regulation mechanisms of human D-amino acid oxidase
No full textThe human peroxisomal FAD-dependent enzyme D-amino acid oxidase (hDAAO, EC 1.4.3.3) plays a key role in important physiological processes by catalyzing the stereospecific degradation of several D-amino acids (D-AAs). A number of studies demonstrated that a dysregulation in processes regulating D-AAs concentration is related to the mechanism(s) predisposing to several pathologies. The important role played by hDAAO in modulating D-AAs levels increased the interest for this flavoenzyme: while structural and biochemical properties have been extensively investigated, several aspects in the modulation of its functionality remain elusive. Furthermore, it has been recently suggested that DAAO could be mistargeted to the nucleus or secreted in the (mouse) intestinal lumen, where it could select the composition of gut microbiota by generating H2O2.
Here, some biochemical properties of the recombinant enzyme were investigated. Moreover, we focused on mistargeting of DAAO by studying a variant lacking the N-terminal signal peptide (thus shedding light on the mechanism of microbiota selection) and two variants at position 120 (a residue belonging to a putative nuclear translocation signal): the cellular targeting of the flavoenzyme seems a way to modulate hDAAO functionality. This modulation allows hDAAO to fulfil different physiological functions, such as the control of the level of D-Ser in the brain and of other D-AAs in different tissues or the selection of microbiota in the gut
Essays on multidimensional poverty measurement and the dependence among well-being dimensions
No full textEvaluating the welfare of nations is high on the research agenda of the economists, practitioners and policy-makers. The literature contributions of the last decades triggered a multivariate perception of the well-being, which is suggested to go beyond the GDP, and created a need for more complex approaches to evaluate the welfare as well as poverty. The first essay investigates the approaches to multivariate poverty measurement and focuses on the composite index approach and the steps involved in it. An important aspect of the multivariate perspective in well-being is the dependence among the underlying indicators. There is a growing evidence in the literature that well-being dimensions are interrelated. This dependence among attributes matters for multidimensional poverty measurement, since income is no longer the only indicator to be considered. However, the reviewed approaches to multivariate poverty measurement do not commonly capture this interdependence. The second essay suggests a copula function as a flexible tool to estimate the dependence among welfare variables. Moreover, it proposes to incorporate the evaluated dependence in the composite indicator. The trade-off among attributes, which is established via the weighting of dimensions, is identified as a possible channel to include the interdependence in the composite indicator. The third essay of this dissertation defines bivariate and multivariate copula-based measures of dependence and applies them using the recent data from the EU-SILC. The results suggest that key dimensions of well-being, i.e. income, education and health, are positively interdependent. In addition, the strength of pairwise and multivariate dependence reinforced in the post-crises period in some European countries. Finally, the last essay proposes a new class of the copula-based multidimensional poverty indices by innovating over the weighting approach. The weighting scheme proposed in this dissertation incorporates the estimated copula-based dependence and contains necessary normative controls to be chosen by the practitioner. The findings of the last essay suggest that the overall poverty is driven not only by the individual shortfalls, but also I by the degree of interdependence among well-being indicators. Considering the proposed copula-based weighting scheme and the proposal of the new class of copula-based poverty indices, this dissertation contributes to the multivariate poverty measurement by suggesting the channel to enclose the dependence structure in the composite indicators. The proposed copula-based methodology will advance the multidimensional poverty analysis and the poverty-reducing policy, which can be designed to address the problem of interdependence of individual achievements