10081 research outputs found
Sort by
EphB1 and Notch4: transmembrane receptors as novel pharmacological targets for glioblastoma and therapeutic angiogenesis
Get PDFThe Eph receptor family of tyrosine kinases and its ligands, ephrins, are membrane-anchored molecules that regulate cell-cell interactions. They are expressed in most cells and tissue types. Eph/ephrin signaling is involved in tumorigenesis, metastasis and angiogenesis. In glioblastoma EphB1 downregulation is correlated with aggressive cancer phenotypes, as this receptor may act as tumor suppressor. Starting from these evidences, we aimed at characterizing the role played by EphB1 receptor in glioblastoma by investigating its expression and modulation in U87 human glioblastoma cells.
The loss of EphB1 receptor expression and its subsequent reduced activity are relevant pro-tumoral events in glioblastoma cells. Consistently, treating U87 cells with the EphB1 receptor agonist or antagonist further reduces or increases cancer cell aggressiveness, respectively. Other different peptides, designed starting from the antagonist already available, affected U87 cell migration.
The Eph/ephrin signaling pathway is also involved in angiogenesis. Therapeutic angiogenesis is an attractive strategy for CAD and PAD patients. VEGF is the master regulator of vascular growth and it represents the major molecular target for therapeutic angiogenesis. Previous studies in the host group show that the induction of normal or aberrant angiogenesis by VEGF depends strictly on the amount secreted in the microenvironment around each producing cell, and not on the total dose delivered. Therefore, here I investigated the Notch4 signaling pathway as a target for therapeutic angiogenesis. We found that Notch4 inhibition: 1) did not impair normal angiogenesis by low and safe levels of VEGF; 2) did not impair the initial formation of vascular enlargements; and 3) normalized aberrant angiogenesis by high VEGF levels of expression by limiting the degree of initial vascular enlargement induced by VEGF
Green supercapacitive systems
Get PDFThis Ph.D. thesis addresses the challenging goal of integrating supercapacitive features in MFCs by sustainable materials and processes and valorizing wastes by their processing as key components of supercapacitors and MFCs. Three main research lines have been pursued: i) the development of green supercapacitors by exploiting natural polymers as binders and electrospun separators, ii) the improvement of the power output of MFCs by the external integration of commercial and green supercapacitors, and ii) the development of supercapacitive microbial fuel cells by the monolithic integration of supercapacitive features in MFCs. This Thesis is articulated in the following Sections. Chapter 1 introduce the energy-water nexus, highlights the role played by supercapacitors and MFCs in this context, and describes the main components, and processes in these devices
Intelligent Sensor Systems for Structural Health Monitoring Applications
Get PDFThe convergence between the recent developments in sensing technologies, data science, signal processing and advanced modelling has fostered a new paradigm to the Structural Health Monitoring (SHM) of engineered structures, which is the one based on intelligent sensors, i.e., embedded devices capable of stream processing data and/or performing structural inference in a self-contained and near-sensor manner.
To efficiently exploit these intelligent sensor units for full-scale structural assessment, a joint effort is required to deal with instrumental aspects related to signal acquisition, conditioning and digitalization, and those pertaining to data management, data analytics and information sharing.
In this framework, the main goal of this Thesis is to tackle the multi-faceted nature of the monitoring process, via a full-scale optimization of the hardware and software resources involved by the {SHM} system. The pursuit of this objective has required the investigation of both: i) transversal aspects common to multiple application domains at different abstraction levels (such as knowledge distillation, networking solutions, microsystem {HW} architectures), and ii) the specificities of the monitoring methodologies (vibrations, guided waves, acoustic emission monitoring). The key tools adopted in the proposed monitoring frameworks belong to the embedded signal processing field: namely, graph signal processing, compressed sensing, ARMA System Identification, digital data communication and TinyML
Complex systems simulations to develop agency and citizenship skills through science education
Get PDFIn the era of big data, the progressively more widespread use of computational and data-intensive approaches is leading to changes in the ways of doing science and conducting research. The new methodologies and techniques are routine for researchers and professionals who make everyday use of big data analytics or simulations tools but are mainly unknown to ordinary people. Nevertheless, the impact of computational and data-intensive approaches has gone far beyond the scientific community, reaching the entire society. Indeed, the applications of machine learning and big data analytics, as well as the results and methods of computational simulations have reached people’s life and behaviour and, even more importantly, are at the methodological core of studies on urgent issues like the climate change or the pandemic, on which policymakers and citizens have to make decisions. Hence, the educational community cannot ignore the ongoing transformation of all people’s lives, behaviors, and culture. Within the research field of education to data science and computation, this dissertation addresses the issue of introducing in teaching-learning activities one of the methods of the on-going data science revolution: the computational simulations. Addressing the conceptual, methodological, and epistemological novelty of these objects, we will show how they embed, in a very specific, disciplinary-grounded way, the paradigm shift and cultural revolution of the data science age. We do that using lenses that come from the science of complexity, with its key-ideas that, originated from the physical modelling, can be applied to the analysis of a range of different phenomena. In the dissertation, we will guide the readers to recognize how dealing with simulations not only requires technical competences of coding, but a change of mindset and ways to think about the problems and the scientific method to address them
Study of the effects of low dose cytokines on a murine preadipocyte line (3T3-L1) and human adipose stem cell (hASC)
Get PDFNella sindrome metabolica l’insulino-resistenza e l’obesità rappresentano i fattori chiave nello sviluppo di tale patologia, ma il principale player risulta un’infiammazione cronica di basso grado (Chronic Low Grade Inflammation) a carico del tessuto adiposo.
Lo scopo di questo progetto di ricerca è quindi stato quello di testare citochine a basso dosaggio come possibile trattamento dell’infiammazione cronica. Le citochine utilizzate (GUNA®-Interleukin 4 (IL-4), GUNA®-Interleukin 10 (IL-10), GUNA®-Melatonin, GUNA®-Melatonin+GUNA®-IL-4.) sono state fornite dall’azienda GUNA S.p.a.
Poiché l’infiammazione cronica a basso grado inizia in seguito ad un aumento eccessivo del tessuto adiposo, inizialmente si è valutato l’effetto su una linea di preadipociti murini (3T3-L1). Questa prima parte dello studio ha messo in evidenza come le citochine a basso dosaggio non modificano la vitalità cellulare, anche se agiscono sull’espressione e la localizzazione di vimentina e E-caderina. Inoltre IL-4 e IL-10 sembrano avere una parziale attività inibitoria, non significativa, sull’adipogenesi ad eccezione dell’espressione dell’adiponectina che appare significativamente aumentata. In ultimo i trattamenti con IL-4 e IL-10 hanno mostrato una diminuzione del contenuto di ROS e una ridotta attività antiinfiammatoria dovuta alla diminuzione di IL-6 secreto.
Un’altra popolazione cellulare principale nel tessuto adiposo è rappresentata dalle ASC (Adipose Stem Cell). Per tale motivo si è proseguito valutando l’effetto che le citochine low-dose su questo citotipo, evidenziando che il trattamento con le citochine non risulta essere tossico, anche se sembrerebbe rallentare la crescita cellulare, e determina un’inibizione del processo adipogenico. Inoltre il trattamento con IL-10 sembra stimolare le ASC a produrre fattori che inducono una maggiore vasculogenesi e le induce a produrre fattori chemiotattici che determinano una maggiore capacità di rigenerazione tissutale da parte di MSC da derma. Infine, il trattamento con IL-4 e IL-10 stimola probabilmente una minore produzione di citochine pro-infiammatorie che inducono in maniera significativa una minore mobilità di cellule MSC.Despite insulin-resistance and obesity represent the key factors in onset and progression of the metabolic syndrome, the main player of related disorders seems to be chronic low-grade inflammation of the adipose tissue. There is evidence that cytokines are relevant regulatory factors of metabolism, in physiological as well as pathological conditions. The aim of our research was to verify if low-dose cytokine administration (lower than fg) could be a possible treatment to counteract chronic inflammation. The tested cytokines, purchased by GUNA S.p.a., were IL-4, IL-10, Melatonin, and a combination of Melatonin and IL-4. Given that chronic low-grade inflammation depends on excessive adipose tissue growth, the effects of cytokines were evaluated on a murine preadipocyte line (3T3-L1). Low-dose cytokines did not modify cell viability, even if they affected the expression and localization of Vimentin and E-cadherin. Furthermore, IL-4 and IL-10 seemed to have a partial inhibitory effect on adipogenesis, although, surprisingly, Adiponectin appeared significantly increased. Furthermore, treatments with IL-4 and IL-10 induced a decrease in ROS content and displayed an anti-inflammatory activity, probably due to the decrease of IL-6 secretion. Adipose tissue, as demonstrated by recent studies, contains a population of stem cells, namely ASCs (Adipose Stem Cells), with a prominent role in homeostatic regulation of the tissue itself. For this reason, the effect of low-dose cytokines on this cytotype has been evaluated, highlighting that the treatment with cytokines was not toxic, even if it seemed to slow down the cell growth, by determining an inhibition of the adipogenic process. In addition, ASCs treated with IL-10 secreted factors able to induce vasculogenesis in Huvec and cell migration in human Mesenchymal Stem Cells. On the contrary, treatments with IL-4 and IL-10 led to a lowering of pro-inflammatory cytokine secretion and a consequent decrease in MSC migratory responses
The Allocation of Asylum Responsibilities in the EU: a Law & Economics Analysis
Get PDFThis dissertation focuses on how the design of the EU asylum allocation system, the system that allocates the EU’s asylum duties to its member states, relates to the development of asylum crises. The current EU asylum allocation system, the Dublin system, has in the literature frequently been blamed as an important factor that contributed to the events that occurred during the 2015/2016 EU Asylum Crisis. In the first part of this dissertation, I use a Law & Economics methodology based on rational choice theory to study how the Dublin system creates behavioural incentives for both asylum seekers and member states and how this relates to the events during the 2015/2016 EU Asylum Crisis. In the second part, I analyse how behavioural incentives for asylum seekers and member states would change if the EU would replace the Dublin system with a so-called (tradable) quota system. By comparing the outcomes of the first and the second part of the dissertation I make some normative recommendations on desirable features for an EU asylum allocation system that provides better incentives for asylum seekers and member states
Machine learning tools for protein annotation: the cases of transmembrane β-barrel and myristoylated proteins
Get PDFBiology is now a “Big Data Science” thanks to technological advancements allowing the characterization of the whole macromolecular content of a cell or a collection of cells. This opens interesting perspectives, but only a small portion of this data may be experimentally characterized. From this derives the demand of accurate and efficient computational tools for automatic annotation of biological molecules. This is even more true when dealing with membrane proteins, on which my research project is focused leading to the development of two machine learning-based methods: BetAware-Deep and SVMyr.
BetAware-Deep is a tool for the detection and topology prediction of transmembrane beta-barrel proteins found in Gram-negative bacteria. These proteins are involved in many biological processes and primary candidates as drug targets. BetAware-Deep exploits the combination of a deep learning framework (bidirectional long short-term memory) and a probabilistic graphical model (grammatical-restrained hidden conditional random field). Moreover, it introduced a modified formulation of the hydrophobic moment, designed to include the evolutionary information. BetAware-Deep outperformed all the available methods in topology prediction and reported high scores in the detection task.
Glycine myristoylation in Eukaryotes is the binding of a myristic acid on an N-terminal glycine. SVMyr is a fast method based on support vector machines designed to predict this modification in dataset of proteomic scale. It uses as input octapeptides and exploits computational scores derived from experimental examples and mean physicochemical features. SVMyr outperformed all the available methods for co-translational myristoylation prediction. In addition, it allows (as a unique feature) the prediction of post-translational myristoylation.
Both the tools here described are designed having in mind best practices for the development of machine learning-based tools outlined by the bioinformatics community. Moreover, they are made available via user-friendly web servers. All this make them valuable tools for filling the gap between sequential and annotated data
“Nanoglial interfaces: nanostructured materials, interfaces and devices to unveil the role of astrocytes in brain function and dysfunction”
Get PDFThe role of non-neuronal brain cells, called astrocytes, is emerging as crucial in brain function and dysfunction, encompassing the neurocentric concept that was envisioning glia as passive components. Ion and water channels and calcium signalling, expressed in functional micro and nano domains, underpin astrocytes’ homeostatic function, synaptic transmission, neurovascular coupling acting either locally and globally. In this respect, a major issue arises on the mechanism through which astrocytes can control processes across scales. Finally, astrocytes can sense and react to extracellular stimuli such as chemical, physical, mechanical, electrical, photonic ones at the nanoscale. Given their emerging importance and their sensing properties, my PhD research program had the general goal to validate nanomaterials, interfaces and devices approaches that were developed ad-hoc to study astrocytes. The results achieved are reported in the form of collection of papers. Specifically, we demonstrated that i) electrospun nanofibers made of polycaprolactone and polyaniline conductive composites can shape primary astrocytes’ morphology, without affecting their function ii) gold coated silicon nanowires devices enable extracellular recording of unprecedented slow wave in primary differentiated astrocytes iii) colloidal hydrotalcites films allow to get insight in cell volume regulation process in differentiated astrocytes and to describe novel cytoskeletal actin dynamics iv) gold nanoclusters represent nanoprobe to trigger astrocytes structure and function v) nanopillars of photoexcitable organic polymer are potential tool to achieve nanoscale photostimulation of astrocytes. The results were achieved by a multidisciplinary team working with national and international collaborators that are listed and acknowledged in the text.
Collectively, the results showed that astrocytes represent a novel opportunity and target for Nanoscience, and that Nanoglial interface might help to unveil clues on brain function or represent novel therapeutic approach to treat brain dysfunctions
The environmental DNA in the risk assessment and decision making processes for the invasive species management in agri-food sector, hydraulic security and biodiversity conservation
Get PDFThe use of environmental DNA (eDNA) analysis as a monitoring tool is becoming more and more widespread. The eDNA metabarcoding methods allow rapid community assessments of different target taxa.
This work is focused on the validation of the environmental DNA metabarcoding protocol for biodiversity assessment of freshwater habitats.
Scolo Dosolo was chosen as study area and three sampling points were defined for traditional and eDNA analyses. The gutter is a 205 m long anthropic canal located in Sala Bolognese (Bologna, Italy).
Fish community and freshwater invertebrate metazoans were the target groups for the analysis.
After a preliminary study in summer 2019, 2020 was devoted to the sampling campaign with winter (January), spring (May), summer (July) and autumn (October) surveys.
Alongside with the water samplings for the eDNA study, also traditional fish surveys using the electrofishing technique were performed to assess fish community composition; census on invertebrates was performed using an entomological net and a surber sampler.
After in silico analysis, the MiFish primer set amplifying a fragment of the 12s rRNA gene was selected for bony fishes. For invertebrates the FWHF2 + FWHR2N primer combination, that amplifies a region of the mitochondrial coi gene, was chosen.
Raw reads were analyzed through a bioinformatic pipeline based on OBITools metabarcoding programs package and QIIME2. The OBITools pipeline retrieved seven fish taxa and 54 invertebrate taxa belonging to six different phyla, while QIIME2 recovered eight fish taxa and 45 invertebrate taxa belonging to the same six phyla as the OBITools pipeline.
The metabarcoding results were then compared with the traditional surveys data and bibliographic records.
Overall, the validated protocol provides a reliable picture of the biodiversity of the study area and an efficient support to the traditional methods
Pausanias'Periegesis digital atlas: methodology, implementations and developements
Get PDFLa tesi consiste nella descrizione del complessivo background storico-letterario, archeologico e digitale necessario per la realizzazione di un Atlante digitale dell’antica Grecia antica sulla base della raccolta e analisi dei dati e delle informazioni contenute nella Periegesi di Pausania. Grazie all’impiego degli applicativi GIS, ed in particolare di ArcGIS online, è stato possibile creare un database georiferito contenente le informazioni e le descrizioni fornite dal testo; ogni identificazione di un sito storico è stata inoltre confrontata con lo stato attuale della ricerca archeologica, al fine di produrre uno strumento innovativo tanto per a ricerca storico-archeologica quanto per lo studio e la valutazione dell’opera di Pausania.
Nello specifico il lavoro consiste in primo esempio di atlante digitale interamente basato sull’interpretazione di un testo classico attraverso un processo di georeferenziazione dei suoi contenuti. Per ogni sito identificato è stata infatti specificato il relativo passo di Pausania, collegando direttamente Il dato archeologico con la fonte letteraria. Per la definizione di una tassonomia efficace per l’analisi dei contenuti dell’opera o, si è scelto di associare agli elementi descritti da Pausania sette livelli (layers) all’interno della mappa corrispondenti ad altrettante categorie generali (città, santuari extraurbani, monumenti, boschi sacri, località, corsi d’acqua, e monti). Per ciascun elemento sono state poi inserite ulteriori informazioni all’interno di una tabella descrittiva, quali: fonte, identificazione, età di appartenenza, e stato dell’identificazione.The thesis consists in the description of the historical, literary, archaeological and digital background nec-essary to the creation of a digital atlas of ancient Greece based on the collection and analysis of the data and informations provided by Pausanias’Periegesis. Through the GIS softwares, and in particular ArcGIS online, it was possible to create a georeferred database embedded with all the text’s data and descrip-tions; every single identification of a historical site was confronted with the current state of the archaeo-logical research, in order to create an innovative tool aimed to both the historical and archaeological re-search and to the study and analysis of Pausanias’ text.
More precisely, this work consisted in a first example of a digital atlas entirely based on the interpretation of a classical text through the georeferencing of its contents. Every location was associated to the relative description by Pausanias, by directly linking the archaeological informations and the literary source. In or-der to define an effective taxonomy for the analysis of the contents of the text, it was decided to associ-ate to each one of the elements described by Pausanias seven layers inside the map, each one describing general categories (towns, suburban sanctuaries, monuments, sacred groves, locations, hydrography and mountains). Every element was eventually embedded with data organized in a contents table, such as: source, identification, historical period and identification status