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Photoredox Catalysis and Nucleophilic Organometallic Reagents – Application in Organic Synthesis
Get PDFThe main purpose of my PhD was the combination of the principles of transition metal catalysis with photoredox catalysis. We focused our attention on the development of novel dual catalytic protocols for the functionalization of carbonyl compounds through the generation of transient nucleophilic organometallic species. Specifically, we focused on the development of new methodologies combining photoredox catalysis with titanium and nickel in low oxidation state. Firstly, a Barbier-type allylation of aromatic and aliphatic aldehydes –catalytic in titanium– in the presence of a blue photon-absorbing dye was developed. Parallelly, we were pleased to observe that the developed methodology could also be extended to the propargylation of aldehydes under analogous conditions. After an extensive re–optimization of all the reaction parameters, we developed an enantioselective and diastereoselective pinacol coupling of aromatic aldehydes promoted by non-toxic, cheap and easy to synthetize titanium complexes. The key feature, that allows the complete (dia)stereocontrol played by titanium, is the employment of a red-absorbing organic dye. The tailored (photo)redox properties of the red-absorbing organic dye [nPr–DMQA+][BF4–] promote the selective reduction of Ti(IV) to Ti(III). Moreover, even if the major contribution in dual photoredox and nickel catalysis is devoted to the realization of cross-coupling-type reactions, we wanted to evaluate different possible scenarios. Our focus was on the possibility of exploiting intermediates arising from the oxidative addition of nickel complexes as transient nucleophilic species. The first topic considered regarded the possibility to perform allylation of aldehydes by dual photoredox and nickel catalysis. In the first instance, a non–stereocontrolled version of the reaction was presented. Finally, after a long series of drastic modification of the reaction conditions, a highly enantioselective variant of the protocol was also reported. All the reported methodologies are supported by careful photophysical analysis and, in some cases, computational modelling
Identification of a novel microRNA-dependent resistance mechanism to inhibition of the PI3K / AKT signaling pathway in prostate cancer
Get PDFBenché le alterazioni della via PI3K/AKT siano molto sudiate a causa del loro ruolo nella tumorigenesi, e rappresentino pertanto un importante bersaglio terapeutico, i risultati di numerosi studi clinici con inibitori di PI3K o AKT sono finora deludenti, in parte a causa dell’insorgenza di resistenza provocata dall'interruzione dei circuiti di feedback negativo.
In questo studio, abbiamo scoperto che l’inattivazione farmacologica di AKT in cellule di carcinoma prostatico PC3 porta alla down-regolazione di un microRNA con funzione di oncosoppressore, il miR-145-5p, e ad un drammatico aumento di espressione di uno dei suoi geni target, cioè N/KRas. E’ interessante sottolineare che questo microRNA è considerato un marker di progressione metastatica nel carcinoma prostatico, il cui livello di espressione aiuta a discriminare tra pazienti con iperplasia prostatica benigna e cancro alla prostata. Inoltre, la bassa espressione di miR-145 aumenta il rischio di progressione della malattia da localizzata a metastatica. La conferma che l’aumento di Ras, osservato sia in termini di mRNA che di proteina, è dipendente dalla caduta del miR-145-5p, è stata poi ottenuta tramite un modello di PC3 ingegnerizzate per ottenere il silenziamento inducibile del miR-145-5p. Tramite un array di fosfoproteine siamo poi stati in grado di verificare che l’aumento di Ras provoca la riattivazione della cascata di PI3K/AKT e di ERK. Dal punto di vista meccanicistico, quindi, lo studio ha portato all’identificazione di un nuovo meccanismo di resistenza adattativa, in cui l’inattivazione di AKT provoca una caduta del miR-145-5p che, a sua volta, aumenta l’espressione di Ras e riattiva il signaling di PI3K, rendendo inefficace il trattamento farmacologico. Questi risultati sono particolarmente rilevanti alla luce di recenti studi (NCT04493853; NCT03072238; NCT02525068) e di trial clinici in corso (NCT04737109; NCT03673787), basati sulla somministrazione combinata di inibitori della sintesi degli androgeni con gli inibitori di AKT capitasertib o ipatasertib.Although aberrantly active PI3K / AKT pathway is regarded as a main therapeutic target due to its role in tumorigenesis. It therefore not surprising that a number of inhibitory drugs have been trialled for both solid and hematological malignancies. however, the results of clinical studies with such PI3K or AKT inhibitors have been so far disappointing, also because of resistance caused by interruption of negative feedback circuits.
In this study, we found that pharmacological inactivation of AKT in PC3 prostate cancer cells leads to down-regulation of a tumor suppressor microRNA, miR-145-5p and to a dramatic increase in the expression of one of its target genes, namely N / KRas. Interestingly, levels of miR-145 help discriminate between benign prostatic hyperplasia and prostate cancer patients, while miR-145 loss increases risk for localized to metastatic disease progression. Low expression of miR-145 is part of a miRNA signature to predict poor survival of PC patients. Confirmation that the observed drop of miR-145-5p triggers an increase of Ras, detected both in terms of mRNA and protein, was obtained using PC3 cells engineered by us to transiently silence the 145-5p guide strand of miR-145 following exposure to doxycycline. Furthermore, through a phosphoprotein array we were then able to validate that such burst of Ras expression elicits reactivation of both the PI3K / AKT and ERK cascades. From a mechanistic point of view, therefore, this study led to the identification of a new adaptive resistance mechanism, in which the inactivation of AKT causes a down-regulation of miR-145-5p, which, in turn, increases Ras expression and reactivates PI3K signaling, lessening drug treatment efficacy. These results are particularly relevant in light of recently published (NCT04493853; NCT03072238; NCT02525068) as well as ongoing (NCT04737109; NCT03673787) clinical trials, based on the combination of androgen deprivation therapy with the AKT inhibitors capitasertib or ipatasertib
Predictive factors for pelvic pain during medical abortion: a prospective observational study
Get PDFINTRODUZIONE Pochi studi in Letteratura hanno indagato la correlazione tra la sintomatologia dolorosa associata all’interruzione farmacologica di gravidanza (IVG) e i livelli d’ansia pre-trattamento. L’obiettivo primario del nostro studio è stato di valutare la correlazione tra la sintomatologia dolorosa in corso di IVG farmacologica e i livelli d’ansia pre-trattamento. Inoltre, sono stati indagati i fattori predittivi di dolore e la correlazione con l’epoca gestazionale.
MATERIALI E METODI È stato condotto uno studio osservazionale, prospettico, multicentrico presso l’Unità Operativa di Ostetricia e Ginecologia dell’Azienda USL e presso l’Unità Operativa di Ginecologia dell’IRCCS Sant’Orsola Malpighi di Bologna. Sono state incluse le pazienti sottoposte a IVG farmacologica tra giugno 2021 e novembre 2021, che rispettassero i criteri di inclusione ed esclusione. Sono stati somministrati 5 questionari (GHQ-12, GAD-7, STAI-6, VAS) e raccolti i dati anamnestici ed ecografici. I potenziali fattori di rischio sono stati, quindi, selezionati per l’inclusione nell'analisi di regressione multivariata.
RISULTATI Delle 242 pazienti incluse, il 38,0% ha riferito una sintomatologia dolorosa severa (VAS >70). Dall’analisi di regressione multivariata, la dismenorrea intensa è risultata essere il fattore di rischio più forte per il dolore (OR = 6,30, IC 95% 2,66 – 14,91), seguita da alti livelli di ansia valutati mediante il punteggio del GHQ-12 > 9 (OR = 3,33, IC 95% 1,43 – 7,76). Al contrario, la nostra analisi ha confermato che un precedente parto vaginale rappresentava una caratteristica protettiva contro il dolore (OR 0,26, IC 95% 0,14 – 0,50).
CONCLUSIONI Nel nostro studio alti livelli d’ansia pre-trattamento e la dismenorrea sono associati ad intensa sintomatologia dolorosa, mentre il parto vaginale è risultato protettivo. L’IVG farmacologica è una metodica efficace e sicura, ma spesso associata a sintomatologia dolorosa. È quindi fondamentale delineare fattori di predittivi di dolore ed individuare le pazienti a maggior rischio a cui somministrare un’idonea terapia antalgica.INTRODUCTION Few studies in Literature have investigated the anamnestic and medical features that might be associated with increased pain levels during medical abortion. The primary aim of our study is to identify the anamnestic and clinical characteristics that may represent risk factors for intense pain levels, with particular focus on women’s pre-treatment psychological distress and anxiety levels. Moreover, we evaluate the correlation between pain and gestational age.
MATERIALS AND METHODS This prospective, observational, non-pharmacological, multicentric study was conducted at the Department of Obstetrics and Gynecology of Azienda USL of Bologna, and at the Department of Gynecology and Human Reproduction Physiopathology of IRCCS S. Orsola – Malpighi Hospital. We included all women who opted for medical treatment for abortion, between June 1st, 2021 and November 30th, 2021. In addition to anamnestic records and ultrasound data, women were asked to fill in the following questionnaires: GHQ-12, GAD-7, STAI-6, VAS. The potential risk factors were, therefore, selected for inclusion in the multivariate regression analysis.
RESULTS On 242 women enrolled, 38.0% experienced severe pain during medical abortion. A previous history of intense dysmenorrhea appeared the strongest risk factor for pain, when evaluating the size effect of each significant predictor (OR = 6.30, 95% CI 2.66 – 14.91), followed by a GHQ-12 score > 9 (OR = 3.33, 95% CI 1.43 – 7.76). On the contrary, our analysis confirmed that a previous vaginal delivery represented a protective feature against intense pain (OR 0.26, 95% CI 0.14 – 0.50).
CONCLUSIONS Our data clearly show that nulliparity, dysmenorrhea, and increased baseline anxiety levels significantly increase the likelihood of severe pain in women undergoing medical abortion. Medical abortion is a safe and effective procedure, but it is often associated with pain symptoms. The identification of women at risk for experiencing severe pain is crucial to improve women’s care
Uterine peristalsis in adenomyosis: a prospective study
Get PDFObiettivi dello studio: valutare con l’ecografia transvaginale la peristalsi uterina in fase periovulatoria in donne con adenomiosi isolata, confrontandola con un gruppo di controllo e, secondariamente, valutare il grado di accordo tra gli sperimentatori nella descrizione dei pattern di contrattilità.
Disegno dello studio: studio osservazione prospettico condotto presso il Policlinico S. Orsola- Malpighi di Bologna, Italia.
Materiali e Metodi: sono state reclutate pazienti afferenti al Centro per valutazione ambulatoriale, suddivise sulla base dei criteri di inclusione ed esclusione nei gruppi A (adenomiosi) e B (controlli) e sono state sottoposte da un unico ecografista esperto a ecografia transvaginale con registrazione di un video della durata di 180 secondi della scansione sagittale dell’utero. La registrazione è stata rivalutata off line da due sperimentatori esperti ecografisti, non a conoscenza della storia clinica delle pazienti e in cieco l’uno rispetto all’altro, che hanno descritto il pattern contrattile. È stata stimata una numerosità campionaria di 18 pazienti per gruppo per ottenere una differenza del 20% nell’obiettivo primario con una significatività del 5% (power 80%).
Risultati: di 51 pazienti reclutate nello studio, a seguito di drop out 36 sono state sottoposte alla videoregistrazione ecografica (18 per gruppo). Il pattern peristaltico nel gruppo A è risultato alterato in maniera statisticamente significativa rispetto al gruppo B con un p value= 0,02. Sono stati osservati un pattern retrogrado nel 27,8% vs 72,2%, anterogrado del 11,1% vs 16,7%, opposto 38,9% vs 5,6% e random nel 22,2% vs 5,6%, rispettivamente nel gruppo A e B. Il calcolo dell’accordo interosservatore ha portato a un κ value di 0,92.
Conclusioni: l’adenomiosi isolata è associata a disperistalsi uterina, che concorrerebbe nello sviluppo dei sintomi tipici dell’adenomiosi. L’ecografia transvaginale rappresenta uno strumento accessibile e utile nella valutazione della contrattilità uterina in quanto il grado di accordo tra gli sperimentatori è ottimo.Objectives: To evaluate uterine peristalsis assessed by transvaginal ultrasound in periovulatory phase in women with adenomyosis compared with a control group and to assess the inter-observer agreement of transvaginal ultrasound in the evaluation of endometrial waves (EW) pattern.
Study design: Observational prospective study conducted in S. Orsola- Malpighi University Hospital, Bologna, Italy.
Materials and Methods: Patients referred to the Centre for an outpatient evaluation were enrolled and subsequently divided in 2 groups according to inclusion and exclusion criteria: patients in group A had a clinical and ultrasonographic diagnosis of adenomyosis, patients in group B had no pathological findings. Three-minute recording of transvaginal ultrasound scanning on sagittal uterine plane at periovulatory phase was performed by a single experienced sonographer gynecologist. Analysis of the EW patterns was performed offline by two different experienced sonographer gynecologists not aware of patients’ clinical history and blinded each other. A sample size of 18 patients per group was calculated to obtain a difference of 20% in the primary objective with a significance of 5% (power 80%).
Results: 51 women were enrolled into this study and 36 patients met the inclusion criteria, 18 per group. The EW pattern was significantly altered when comparing the women with adenomyosis and control (p value= 0,02). Retrograde contractions were observed in 27,8% vs 72,2%, anterograde contractions in 11,1% vs 16,7%, opposing in 38,9% vs 5,6%, random in 22,2% vs 5,6%, respectively, in adenomyosis group versus the control group. EW evaluation showed a perfect inter-observer agreement (κ value= 0,92).
Conclusions: Adenomyosis is associated with altered uterine contractility, which may aid in explaining the symptoms related with. Ultrasound imaging is an easy to access and useful method to evaluate uterine peristalsis, with a perfect inter-observer agreement
The Public space design at the time of the trust. Methods and projects in urban and peripheral contexts
Get PDFLo spazio pubblico urbano potrebbe essere visto come una scenografia mutevole in cui la società rappresenta sé stessa. Soprattutto nei centri storici della città, si perde l’identità di luoghi specifici, così come la coscienza dei cittadini, che porta ad un uso improprio dello spazio causato principalmente dall’assenza di una cultura architettonica. In questo senso, l’obiettivo finale dell’architettura è quello di essere educativa nello spiegare il motivo per cui è stata concepita.
La tesi di ricerca tenta di studiare la dimensione educativa e la forza che l’architettura ha nell’influenzare comportamenti spontanei e non spontanei. L’obiettivo è trovare metodi di progettazione e legali in grado di migliorare gli spazi pubblici in termini di qualità della vita dei suoi utenti. Il riconoscimento e la trasmissione dell’architettura, attraverso l’uso dell’architettura stessa, tenta di arginare un’assenza di cultura architettonica e un uso sempre più improprio dei suoi spazi. La domanda a cui, dunque, si tenta di rispondere è: Può la dimensione evocativa dell’architettura stimolare processi di rigenerazione urbana?
La tesi si sviluppa in tre parti: la prima presenta alcune riflessioni teoriche sulla progettazione dello spazio pubblico alle quali fanno riferimento altrettanti progetti portati avanti nei mesi di ricerca Dai workshops realizzati sono emerse diverse problematiche riguardo l’effettiva realizzazione di tali progetti evidenziando soprattutto una carenza di tipo normativo che fa “cadere” gli entusiasmi legati al completamento delle opere per la comunità e di conseguenza decade il valore teorico dei progetti. Per questo motivo, nella seconda parte, si tenta di approfondire il tema legislativo per trovare soluzioni alternative agli arresti burocratici che sovente disincentivano le azioni corali della cittadinanza. La terza parte si concentrerà su un progetto per un’area di Bologna da riqualificare, i Prati di Caprara, per i quali si sfrutteranno tutte le conoscenze teoriche precedentemente esposte.Urban public space could be seen as a changing setting in which society represents itself. Especially in the historical centers of the city, the identity of specific places is lost, as well as the awareness of citizens, which leads to an improper use of space caused mainly by the absence of an architectural culture. In this sense, the ultimate goal of architecture is to be educational in explaining why it was conceived.
The research thesis attempts to study the educational dimension and the strength that architecture has in influencing spontaneous and not spontaneous behaviors. The goal is to find design and legal methods that can improve public spaces in terms of quality of life of its users. The recognition and transmission of architecture, through the use of architecture itself, tries to stem an absence of architectural culture and an increasingly improper use of its spaces. The question that the research tries to answer is: Can the evocative dimension of architecture stimulate processes of urban regeneration?
The thesis is developed in three parts: the first presents some theoretical reflections on the design of public space to which refer as many projects carried out in recent months. From the workshops realized they have emerged various problematic with regard to the effective realization of such plans evidencing above all a deficiency of normative type. For this reason, in the second part, an attempt is made to deepen the legislative theme in order to find alternative solutions to the bureaucratic arrests that often discourage the collective actions of the citizens.
The third part will focus on a project for an area of Bologna to be redeveloped, the Prati di Caprara, for which will exploit all the theoretical knowledge previously exposed
The "anxious" enquiry. Representing, knowing, interpreting: poetics and auctorial postures (Zola, Capuana and Pardo Bazan)
Get PDFMa thèse interroge les formes, les modes et les enjeux liés à la notion d’« enquête » dans les discours et les poétiques d’Émile Zola, Luigi Capuana et Emilia Pardo Bazán. Il s'agit d’abord de prendre au sérieux l’ambition à l’« enquête totale » du roman naturaliste européen vers 1880, envisagée par le credo zolien du « tout dire », par l'idée de la forme « ancha, completa y perfecta » de Pardo Bazán et par l'éclectisme boulimique de Capuana. Corollairement, le lecteur de l’époque, demandeur de « récit », expérimente une pratique esthétique marquée par la porosité disciplinaire et la diversité de formats et de supports. Par l’épistémocritique, la sociocritique et la « sémiologie historicisée », il s’agit donc de questionner les relations entre scientifique et littéraire, fictionnel et factuel, vrai et faux, et leurs présupposés épistémologiques et idéologiques, qui sont définis et redéfinis par les trois auteurs à l’aune de leurs postures et de leurs stratégies d’affirmation spécifiques. En accord avec le « décloisonnement » disciplinaire à l’œuvre à l’époque, d’un point de vue de la réception ainsi que de la production, le corpus mobilisé rapproche des romans, des chroniques, des textes théoriques et critiques, mais aussi des textes « savants » produits ou consultés par les auteurs. À travers l’ensemble de ces perspectives, cette thèse tente d’éclairer, par une démarche comparée, la singularité historique d’une enquête « inquiète » dans le dernier tiers du XIXe siècle.My thesis investigates the forms, modes and issues associated with the notion of 'enquiry' in the discourses and poetics of Émile Zola, Luigi Capuana and Emilia Pardo Bazán. It will do so first by taking seriously the ambition for 'total enquiry' in the European naturalist novel around 1880, such as it is considered by Zola's credo of “tout dire”, by Pardo Bazán's idea of the “ancha, completa y perfecta” form and by Capuana's bulimic eclecticism. As a corollary, the reader of the time, in search of “narrative”, experiences an aesthetic practise marked by disciplinary porosity and the diversity of formats and media. Through epistemocriticism, sociocriticism and "historicised semiology", the aim is therefore to question the relationships between the scientific and the literary, the fictional and the factual, the true and the false, and their epistemological and ideological presuppositions, which the three authors define and redefine in the light of their postures and their specific strategies of affirmation. In line with the disciplinary “decompartmentalization” at work at the time, from the point of view of both reception and production, the assembled corpus brings together novels, chronicles, theoretical and critical texts, but also "scholarly" texts written or consulted by the authors. Through all of these perspectives, this thesis intends to shed light, through a comparative approach, on the historical singularity of an “anxious” enquiry in the last third of the 19th century
Embedded systems and advanced signal processing for Acousto- Ultrasonic Inspections
Get PDFNon Destructive Testing (NDT) and Structural Health Monitoring (SHM) are becoming essential in many application contexts, e.g. civil, industrial, aerospace etc., to reduce structures maintenance costs and improve safety. Conventional inspection methods typically exploit bulky and expensive instruments and rely on highly demanding signal processing techniques. The pressing need to overcome these limitations is the common thread that guided the work presented in this Thesis.
In the first part, a scalable, low-cost and multi-sensors smart sensor network is introduced. The capability of this technology to carry out accurate modal analysis on structures undergoing flexural vibrations has been validated by means of two experimental campaigns. Then, the suitability of low-cost piezoelectric disks in modal analysis has been demonstrated. To enable the use of this kind of sensing technology in such non conventional applications, ad hoc data merging algorithms have been developed.
In the second part, instead, imaging algorithms for Lamb waves inspection (namely DMAS and DS-DMAS) have been implemented and validated. Results show that DMAS outperforms the canonical Delay and Sum (DAS) approach in terms of image resolution and contrast. Similarly, DS-DMAS can achieve better results than both DMAS and DAS by suppressing artefacts and noise. To exploit the full potential of these procedures, accurate group velocity estimations are required. Thus, novel wavefield analysis tools that can address the estimation of the dispersion curves from SLDV acquisitions have been investigated. An image segmentation technique (called DRLSE) was exploited in the k-space to draw out the wavenumber profile. The DRLSE method was compared with compressive sensing methods to extract the group and phase velocity information. The validation, performed on three different carbon fibre plates, showed that the proposed solutions can accurately determine the wavenumber and velocities in polar coordinates at multiple excitation frequencies
Breaking the Doxa? Gender segregation in the labour market
Get PDFLa segregazione nel mercato del lavoro ha dimostrato di essere un fenomeno molto regolare. Osservando i principali indicatori sintetici, troveremo che circa la metà della forza lavoro femminile dovrebbe cambiare lavoro per potersi distribuire fra le professioni nello stesso modo degli uomini, un dato che negli ultimi decenni non sembra essere cambiato. La ricerca si è concentrata sulla socializzazione e come le strutture influenzano l'agency quando le persone pianificano le loro carriere. Tuttavia, riteniamo sia stato ignorato il ruolo della classe occupazionale d'impiego nel dare forma alla segregazione. Facendo riferimento a Bourdieu, la tesi svolge un'analisi empirica su cinque classi occupazionali: dirigenti, professioni intellettuali, tecnici, colletti blu, e professioni non qualificate e dei servizi, stimando modelli logit per calcolare le probabilità delle donne di accedere alle professioni male-dominated, dove gli uomini sono più dei due terzi della forza lavoro. Di particolare interesse è il ruolo della scelta di perseguire un'istruzione STEM e come il campo di studio moderi la relazione fra genere e probabilità di accedere ad una professione male-dominated. I risultati mostrano differenze rilevanti fra le classi occupazionali, e anche fra diversi tipi di campi di studio STEM, suggerendo che la segregazione sia un fenomeno a geometrie variabili che può essere "spezzata" più facilmente in alcune classi rispetto ad altre.Segregation in the labor market has proved to be a surprisingly regular phenomenon. When we look at the main synthetic measures of segregation, we will find that half of the female workforce should change jobs to be distributed among occupations the same way men do, which is the same evidence collected more than twenty-five years ago. Research has focused on socialization and how structures affect agency when people plan their careers. However, previous research on segregation has often neglected the occupational class of employment and its role in shaping segregation.
Using a "Bourdieusian" framework, this paper carries an empirical investigation on segregation in five occupational groups: managers, professionals, technicians, blue-collar workers, and elementary and service workers, computing a logit model for studying women's probabilities of access to male-dominated occupation, where men are more than two-thirds of the workforce. Of specific interest is choosing to pursue a STEM education and how this choice moderates the relation between gender and the probability of accessing a male-dominated occupation. Results show relevant differences in each class, and different STEM fields as well, suggesting that segregation may be “broken” more easily in certain occupational classes than in other ones
Aristotle’s modal syllogistic and first-order modal logic
Get PDFIn Prior Analytics 1.1–22, Aristotle develops his proof system of non-modal and modal propositions. This system is given in the language of propositions, and Aristotle is concerned with establishing some properties and relations that the expressions of this language enjoy. However, modern scholarship has found some
of his results inconsistent with positions defended elsewhere. The set of rules of inference of this system has also caused perplexity: there does not seem to be a single interpretation that validates all the rules which Aristotle is explicitly committed to using in his proofs. Some commentators have argued that these and other problems cannot be successfully addressed from the viewpoint of the traditional, ‘first-order’ interpretation of Aristotle’s syllogistic, whereby propositions are taken to involve quantification over individuals only. Accordingly, this interpretation not only is inadequate for formal analysis, but also stems from a misunderstanding of Aristotle’s ideas about quantification. On the contrary, in this study I purport to vindicate the adequacy and plausibility of the first-order interpretation. Together with some assumptions about the language of propositions and an appropriate regimentation, the first-order interpretation yields promising solutions to many of the problems raised by the modal syllogistic. Thus, I present a reconstruction of the language of propositions and a formal interpretation thereof which will prove respectful and responsive to most of the views endorsed by Aristotle in the ‘modal’ chapters of the Analytics
Interpretable Convolutional Neural Networks for Decoding and Analyzing Neural Time Series Data
Get PDFMachine learning is widely adopted to decode multi-variate neural time series, including electroencephalographic (EEG) and single-cell recordings. Recent solutions based on deep learning (DL) outperformed traditional decoders by automatically extracting relevant discriminative features from raw or minimally pre-processed signals.
Convolutional Neural Networks (CNNs) have been successfully applied to EEG and are the most common DL-based EEG decoders in the state-of-the-art (SOA). However, the current research is affected by some limitations. SOA CNNs for EEG decoding usually exploit deep and heavy structures with the risk of overfitting small datasets, and architectures are often defined empirically. Furthermore, CNNs are mainly validated by designing within-subject decoders. Crucially, the automatically learned features mainly remain unexplored; conversely, interpreting these features may be of great value to use decoders also as analysis tools, highlighting neural signatures underlying the different decoded brain or behavioral states in a data-driven way. Lastly, SOA DL-based algorithms used to decode single-cell recordings rely on more complex, slower to train and less interpretable networks than CNNs, and the use of CNNs with these signals has not been investigated.
This PhD research addresses the previous limitations, with reference to P300 and motor decoding from EEG, and motor decoding from single-neuron activity. CNNs were designed light, compact, and interpretable. Moreover, multiple training strategies were adopted, including transfer learning, which could reduce training times promoting the application of CNNs in practice. Furthermore, CNN-based EEG analyses were proposed to study neural features in the spatial, temporal and frequency domains, and proved to better highlight and enhance relevant neural features related to P300 and motor states than canonical EEG analyses. Remarkably, these analyses could be used, in perspective, to design novel EEG biomarkers for neurological or neurodevelopmental disorders. Lastly, CNNs were developed to decode single-neuron activity, providing a better compromise between performance and model complexity