1731 research outputs found
Sort by
A Systems and Synthetic Biology Framework for Regulatory Systems
Full text linkBiological regulatory systems are complex due to their role in living organisms in modulating precise responses to changes in internal and external conditions. In this respect, mathematical models have become essential tools to address their complexity for a better understanding
of their mechanisms. The vision here, based on integrating experimental and theoretical techniques, provides a systematic means to quantitatively study the characteristics of the interactions that occur in living organisms. The outcome of such an endeavour should provide insights in terms of predictions and quantifications for further investigations in systems and synthetic biology.
In this thesis, we establish an integrated modelling framework that can ensure the interaction of experimental biology with the development of quantitative mathematical descriptions of biological systems. To this end, we develop a framework to simulate and analyse biological
regulatory systems by integrating different layers of regulatory information. The work herein presents a biological model development workflow in terms of a step by step approach, highlighting challenges and “real life” problems associated with each stage of model development.
In the first part, we have focused on applying systems and synthetic biology modelling tools to the phosphate system at the cellular and genetic levels in Escheria coli. Then, we have analysed the interaction mechanisms and the dynamic behaviour of the phosphate starvation response deactivation and evaluated the role of phosphatase activity. We have investigated how the properties of these signalling systems depend on the network structure. Moreover, we have constructed detailed transcriptional regulatory network models and models for promoter design. In the second part, we have designed a multi-level dynamical set up by providing
a novel closed loop whole body model of glucose homeostasis coupled with molecular signalling. We have then developed a system embracing the intracellular metabolic level, the
cellular level involving the dynamics of the cells, the organ level, and the processes within the whole body. The output of each model directly has been fed with the variables and the parameters of the next aggregated model. This allowed us to observe the metabolic changes that occur at all levels and monitor inter-level communications for Type 2 Diabetes disease
Identification of REST-Regulated Molecular Circuitries and Targets Exploitable for hGSCs-Targeted Therapies
Full text linkGlioblastoma (GBM) represents the most frequent and lethal cancer affecting the central nervous system for which no cure is currently available. The presence of Glioma Stem Cells (GSCs) has been proposed to be at the root of therapeutic failures due to their intrinsic abilities of escaping common treatments and relapsing the pathology. Thus, advances in therapeutic options may derive from the manipulation of mechanisms controlling the GSCs self-renewal, survival and functions. RE1-Silencing Transcription Factor (REST) is a master repressor of neuronal developmental programme in non-neuronal lineages, recently described as a main actor in the maintenance of the GSCs’ tumorigenic competence as its knockdown strongly impairs GSCs stemness both in vitro and in vivo. However, REST is critical for restraining neuronal cellular identity in various tissues, so that a targeted therapy to this transcriptional repressor is likely to present numerous side effects. Here, by taking advantage of a Tet-on system for the manipulation of REST expression in both human GSCs and Neural Stem Cell lines (hNSCs), we performed a transcriptomic profiling analysis in order to identify novel tumour-specific REST-regulated functions and molecular targets. Our analyses confirmed the previously reported roles of REST in neural tissues and enlightened novel REST functions in hGSCs, including the regulation of alternative hGSCs identity/state. Finally, analysis of hGSC-specific REST-regulated genes in GBM patients’ dataset revealed an inverse correlation with glioma aggressiveness, thus establishing a hGSC REST score that might provide a useful prognostic tool
Motion in China:Social Inclusion of Migrant Workers from Rural to Urban Areas
Full text linkThis study investigates what’s known as the world’s largest human migration from rural to urban areas. It examines both the destinations and the origins of the mobility trajectories of Chinese internal migrant workers which is somewhat neglected by current literature. Based on a multi-sited ethnography of the daily life of migrant workers in arrays of social setting (sheds in construction sites, urban villages, factories, restaurants) in their urban stay as well as the well-known left behind population in a rural village, the thesis explores the social and economic changes that this mass regional mobility brought to both rural and urban China. The implication of this work lies in a comprehensive and thorough examination on the regional rural-urban migration. It contributes to a dynamic assess, which deserves to study further, by providing an analysis on all the agents involved in the context of Chinese rural-urban migration: the left behind population in villages, the migrant workers and the urban citizens in cities
Cellulose-based BioNanoMaterials:Structure and Properties
Full text linkBiological materials such as wood show outstanding properties due to the self assembly of components from molecular to macroscopic size. An emerging nanotechnology-based strategy consists of the isolation of biological components with size in the range from nanometers to micrometers and of the design of human-driven assembly processes to obtain multifunctional materials.
The aim of this thesis was to isolate cellulose nanocrystals, with dimensions of around 4-5 nm in width and some hundred nanometers in length, and investigate their assembly processes through weak interactions among them and with small molecules, like water or ions. Knowing their interaction properties and self-assembly is indeed fundamental in order to fully exploit the potential of nanocellulose in its recently emerging applications. In particular, I focused on cellulose nanocrystals supramolecular self-organization both in absence and presence of water, studying cellulose nanocrystals-based films and hydrogels.
In dry conditions, the self-assembly of cellulose nanocrystals on a polylactic support was demonstrated to form few micrometers thick films, characterized by a densely packed arrangement of the crystals leaving elongated cavities of about 0.31 nm cross section between them. These cavities provide the pathway for gaseous 2H2 diffusion. Conversely, these films are impermeable barriers for the transport of gaseous molecules such as O2 and CO2.
In aqueous solution, instead, cellulose nanocrystals undergo sonication- or cation-assisted entanglement, forming soft hydrogels. Na+, Ca2+ and Al3+ crosslink the nanocrystals and produce stable hydrogels with structurally ordered domains in which water is confined. Since the gelation process is diffusion controlled, small hydrogel objects with different size and shape have been designed by the coordination-driven assembly of supramolecular rod-like cellulose crystallites, using ionotropic gelation as a methodological approach and Ca2+ as a gelling agent.
In parallel to material characterization, particular attention was devoted to the possible exploitation of cellulose nanocrystals-based materials in the biomedical field. In this regard, toxicity studies were performed both on the individual nanocrystals and on the films and hydrogels resulting from their assembly. Moreover, a hybrid cellulose-nanocrystals/chitosan material was developed and characterized, which shows some potential to be used as therapeutic delivery system in the gastrointestinal tract. Indeed, though a mould assisted gelation process, composite hydrogels can be produced, which are degraded by human digestive enzymes and release a model protein according to a biphasic kinetic profile
Distributed Monitoring for User Localization and Profiling in Smart Environment
Full text linkThe study of the next-generation distributed systems for distributed monitoring and user localization in smart environment is treated in this thesis. In the last years, a growing amount of attention has been focused on the adoption of Wireless Sersor Networks (WSN) as a scalable and flexible backbone to implement innovative services in smart environments, like smart building and smart cities. In this framework, this thesis will describe heterogeneous solutions to improve the supervision, control, monitoring, and management of public and private spaces. All these systems exploit the wireless communication and sensing in combination with smart methodologies to provide advanced services to the end user in many application fields, from environmental monitoring to energy management in smart districts or private and public buildings, up to road security and indoor occupancy for management and security reason. The data acquired by the WSN technology are used as input of customized strategies and algorithms developed for the real-time processing, fast analysis and result visualization
Automatic Analysis of Agreement and Disagreement in the Political Domain
No full textIn this thesis we investigate the automatic analysis of agreement and disagreement in political documents. Our focus is on the comparison of statements about specific topics extracted from documents with no direct interaction (e.g. electoral speeches or political manifestos), in which politicians may express, sometime in an implicit way, their position. This is a challenging task, made difficult also due to the lack of annotated resources.
Our contribution can be divided into two main areas. The first one is the creation of manually and automatically annotated corpora for the task (pairs of statements annotated for agreement or disagreement from different sources). The second one is a Natural Language Processing (NLP) pipeline for the automatic (supervised) classification of agreement and disagreement. This pipeline involves a novel approach to extract well-defined and accurate topics based on key-concept clusters, and two classifiers to identify the pairs of statements in agreement and disagreement (or holding no relation) according to a wide set of features, such as sentiment, entailment, and semantic representation of the topics.
We think that our findings can effectively support political science researchers dealing with an increasing amount of digital data, providing insight into similarities and differences in ideologies
Study of the properties of cemented carbides from industrial production
Full text linkCemented carbides are composite materials formed by high amount of WC bonded by a soft phase, usually Co. They are used in many applications, such as drawing dies, cutting tools and hot rolls due to theirs remarkable properties of high hardness and wear resistance. Mechanical properties are strongly related to microstructure, namely the binder amount and the carbide grain size. Increasing the binder content and the carbide grain size, the hardness decreases ad the fracture toughness increases. In this PhD, the correlations between the mechanical properties of WC-Co and the microstructural characteristics, in parts taken from industrial production, were defined. After that, the influence of the residual microporosity on the mechanical properties was evaluated. Considering the production process, another important modification of the final microstructure of WC-Co occurs due to the liquid cobalt migration phenomenon. Based on this, also the liquid cobalt migration that occurs during sintering was investigated. At the end of the thesis, since a few data are available in literature, Thermal Fatigue and oxidation damage in WC-Co were studied. The main results of this PhD thesis show that the hardness and fracture toughness of WC-Co are defined by the mean binder free path and not by the contiguity since the high standard deviations, the microstructural fineness and also the high carbide grain size scatter. Differently, in case of mechanical strength, also the residual microporosity that depends on the dewaxing stage must be defined. Furthermore, the dewaxing stage acts on the liquid cobalt migration that affects the surface properties and also the final microstructure of the WC-Co part in industrial production. At the end, considering the damages that occur during high temperature applications, the TF and oxidation resistance of WC-Co results affected by the Co content: high cobalt content leads to a better condition of TF damage and s higher oxidation resistance
Uso del tempo e performance accademiche. Nuove tecniche e prospettive con l'utilizzo dei Big Data
Full text linkQuesta tesi di dottorato affronta e approfondisce tre temi diversi ma legati tra loro: le performance accademiche degli studenti nell'istruzione terziaria, l'uso del tempo e l'utilizzo dei Big Data nelle scienze sociali. Gli obiettivi che hanno fatto nascere questo lavoro, attraverso un approccio a tratti interdisciplinare, sono stati, in primo luogo, cercare di colmare empiricamente alcune lacune legate a interrogativi di ricerca rimasti parzialmente senza risposta in letteratura e, in secondo luogo, proporre soluzioni metodologiche connesse soprattutto alla raccolta dei dati e alla loro affidabilità nel rispondere a questi interrogativi in un modo quanto più possibile coerente con la realtà .
La tesi non ha una struttura monografica in quanto i quattro capitoli empirici hanno una struttura propria. Il primo capitolo empirico vuole essere un inquadramento generale dell'intera tesi che mira a indagare l'effetto del capitale culturale familiare sia sulle performance accademiche degli studenti, sia su alcuni aspetti legati alla gestione che essi fanno del proprio tempo che, tradizionalmente, sono associati a una buona riuscita accademica, ipotizzando che l'origine sociale non esaurisca il suo effetto nei livelli d'istruzione precedenti. I modelli di equazione strutturali, attraverso l'analisi multi-gruppo, hanno consentito di costruire l'analisi in un'ottica comparativa rispetto al settore disciplinare di appartenenza. Il secondo capitolo approfondisce la dimensione temporale, ovvero come gli studenti organizzano le attività durante le loro giornate, al fine di comprendere come essa possa influire sui risultati universitari. L'obiettivo principale è stato colmare alcune lacune empiriche presenti in letteratura che mostrano risultati contrastanti su questo tema, dettati soprattutto da problemi di raccolta dati, non sempre adatti a indagare l'uso che gli studenti fanno del proprio tempo. Anche questo capitolo propone uno sguardo comparativo, confrontando degli studenti del primo anno, cioè gli studenti più a rischio rispetto al gestire il proprio tempo in modo poco efficace, con gli studenti degli anni successivi. Il terzo capitolo descrive il progetto SmartUnitn, fulcro di questo lavoro di tesi al fine di evidenziare come l'utilizzo di ICTs è in questo caso gli smartphone nella fase di raccolta dati possa contribuire a migliorare la qualità del dato ottenuto andando a risolvere alcune questioni problematiche derivanti dagli strumenti tradizionali utilizzati dagli scienziati sociali. Il quarto e ultimo capitolo, propone un caso concreto di utilizzo dei dati ottenuti dall'esperimento SmartUnitn, proponendo un metodo che, grazie all'unione dei dati dei sensori e i dati delle risposte degli studenti, possa colmare alcune lacune presenti in letteratura sul tema dell'influenza dell'utilizzo dei social media sui risultati universitari
Attentional Mechanisms in Natural Scenes
Full text linkThe visual analysis of the world around us is an incredibly complex neural process that allows humans to function appropriately within the environment. When one considers the intricacy of both the visual input and the (currently known) neural mechanisms necessary for its analysis, it is difficult not to remain enchanted by the fact that, even though the signal that hits the retina has a tremendous amount of simple visual features and that is ever changing, ambiguous and incomplete, we experience the world around us in a very easy, stable and straightforward manner. So much effort has been put into the study of vision, and despite the enormous scientific advances and important findings, many questions still need answers.
During my years spent as Ph.D. student, I investigated some questions related to top-down attentional mechanisms in real-world visual search. Specifically, Chapter 2 and 3 address the processing stage of preparation, by investigating the characteristics of attentional templates when preparing to search for objects in scenes; Chapter 4 addresses the stage of guidance and selection, by investigating the temporal course of spatial attention guidance; and finally, Chapter 5 addresses the identification phase, by investigating the temporal dynamics of size-constancy mechanisms in real-world scenes.
To anticipate some results, we proposed that attentional templates in real-world visual search tasks are based on category-diagnostic features and code the expected target size/distance. In the context of the attentional guidance and selection stage, we demonstrate that attention spatially focuses on targets around 240ms, following category-based attentional modulations appearing at 180ms after scene onset. Finally, we propose that size constancy mechanisms appear before 200ms post-scene. This is in line with the expectation that a coarse identification of an object, including its size, should be computed before spatially focusing attention onto the target. Together these studies improve our understanding of top-down attentional processes engaged in real-world visual search, and raise some questions which future research could address
Dynamic Adaptation of Service-Based Systems: a Design for Adaptation Framework
No full textA key challenge posed by the Next Generation Internet landscape, is that modern service-based systems need to cope with open and continuously evolving environments and to operate under dynamic circumstances. Dynamism is given by changes in the operational context, changes in the availability of resources and variations in their behavior, changes in users goals, etc. Indeed, dynamically discover, select and compose the appropriate services in open and expanding domains is a challenging task. Many approaches for self-adaptive systems have been proposed in the last decades. Unfortunately, although they support run-time adaptation, current approaches tend to foresee the system adaptation requirements and their related solutions at design-time. This makes them inadequate for the application
in open environments, where components constantly join/leave the system, since they require for continuous involvement of IT and domain experts for the systems re-configuration. We claim that a new way of approaching the adaptation of systems is needed. In this dissertation, we propose a novel design for adaptation framework for modeling and executing modern service-based systems. The idea of the approach consists in defining the complete life-cycle for the continuous development and deployment of service-based systems, by facilitating (i) the continuous integration of new services that can easily join the systems, and (ii) the systems operation under dynamic circumstances, to face the
openness and dynamicity of the environment.
Furthermore, Collective Adaptive Systems (CAS) are spreading in new emerging contexts, such as the shared economy trend. Modern systems are expected to handle a multitude of heterogeneous components that cooperate
to accomplish collective tasks. In these settings, an extension of our framework in the direction of CAS has also been defined. The core enablers of the proposed framework have been implemented and evaluated in real-world scenarios in the mobility domain. Promising evaluation results demonstrate their practical applicability