A take on complexity: bio-molecules and human metabolism interaction modelling for health and nutrition with machine learning

The advent of omic data production has opened many new perspectives in the quest for modelling complexity in biophysical systems. With the capability of characterizing a complex organism through the patterns of its molecular states, observed at different levels through various omics, a new paradigm of investigation is arising. In this thesis, we investigate the links between perturbations of the human organism, described as the ensemble of crosstalk of its molecular states, and health. Machine learning plays a key role within this picture, both in omic data analysis and model building. We propose and discuss different frameworks developed by the author using machine learning for data reduction, integration, projection on latent features, pattern analysis, classification and clustering of omic data, with a focus on 1H NMR metabolomic spectral data. The aim is to link different levels of omic observations of molecular states, from nanoscale to macroscale, to study perturbations such as diseases and diet interpreted as changes in molecular patterns. The first part of this work focuses on the fingerprinting of diseases, linking cellular and systemic metabolomics with genomic to asses and predict the downstream of perturbations all the way down to the enzymatic network. The second part is a set of frameworks and models, developed with 1H NMR metabolomic at its core, to study the exposure of the human organism to diet and food intake in its full complexity, from epidemiological data analysis to molecular characterization of food structure.

Development and optimization of graphic user interfaces (GUIs) for infrared spectrometers at the Telescopio Nazionale Galileo

This Phd thesis was entirely developed at the Telescopio Nazionale Galileo (TNG, Roque de los Muchachos, La Palma Canary Islands) with the aim of designing, developing and implementing a new Graphical User Interface (GUI) for the Near Infrared Camera Spectrometer (NICS) installed on the Nasmyth A of the telescope. The idea of a new GUI for NICS has risen for optimizing the astronomers work through a set of powerful tools not present in the existing GUI, such as the possibility to move automatically, an object on the slit or do a very preliminary images analysis and spectra extraction. The new GUI also provides a wide and versatile image display, an automatic procedure to find out the astronomical objects and a facility for the automatic image crosstalk correction. In order to test the overall correct functioning of the new GUI for NICS, and providing some information on the atmospheric extinction at the TNG site, two telluric standard stars have been spectroscopically observed within some engineering time, namely Hip031303 and Hip031567. The used NICS set-up is as follows: Large Field (0.25'' /pixel) mode, 0.5'' slit and spectral dispersion through the AMICI prism (R~100), and the higher resolution (R~1000) JH and HK grisms.

Bifidobacterium - Human Host Interaction: Role of Human Plasminogen

Bifidobacterium is an important genus of the human gastrointestinal microbiota, affecting several host physiological features. Despite the numerous Bifidobacterium related health-promoting activities, there is still a dearth of information about the molecular mechanisms at the basis of the interaction between this microorganism and the host. Bacterial surface associated proteins may play an important role in this interaction because of their ability to intervene with host molecules, as recently reported for the host protein plasminogen. Plasminogen is the zymogen of the trypsin-like serine protease plasmin, an enzyme with a broad substrate specificity. Aim of this thesis is to deepen the knowledge about the interaction between Bifidobacterium and the human plasminogen system and its role in the Bifidobacterium-host interaction process. As a bifidobacterial model, B. animalis subsp. lactis BI07 has been used because of its large usage in dairy and pharmaceutical preparations. We started from the molecular characterization of the interaction between plasminogen and one bifidobacterial plasminogen receptor, DnaK, a cell wall protein showing high affinity for plasminogen, and went on with the study of the impact of intestinal environmental factors, such as bile salts and inflammation, on the plasminogen-mediated Bifidobacterium-host interaction. According to our in vitro findings, by enhancing the activation of the bifidobacterial bound plasminogen to plasmin, the host inflammatory response results in the decrease of the bifidobacterial adhesion to the host enterocytes, favouring bacterial migration to the luminal compartment. Conversely, in the absence of inflammation, plasminogen acts as a molecular bridge between host enterocytes and bifidobacteria, enhancing Bifidobacterium adhesion. Furthermore, adaptation to physiological concentrations of bile salts enhances the capability of this microorganism to interact with the host plasminogen system. The host plasminogen system thus represents an important and flexible tool used by bifidobacteria in the cross-talk with the host.

Safe and Collaborative Navigation & Interaction With Mobile Manipulators in Domestic Appliance Test Labs

Safe collaboration between a robot and human operator forms a critical requirement for deploying a robotic system into a manufacturing and testing environment. In this dissertation, the safety requirement for is developed and implemented for the navigation system of the mobile manipulators. A methodology for human-robot co-existence through a 3d scene analysis is also investigated. The proposed approach exploits the advance in computing capability by relying on graphic processing units (GPU’s) for volumetric predictive human-robot contact checking. Apart from guaranteeing safety of operators, human-robot collaboration is also fundamental when cooperative activities are required, as in appliance test automation floor. To achieve this, a generalized hierarchical task controller scheme for collision avoidance is developed. This allows the robotic arm to safely approach and inspect the interior of the appliance without collision during the testing procedure. The unpredictable presence of the operators also forms dynamic obstacle that changes very fast, thereby requiring a quick reaction from the robot side. In this aspect, a GPU-accelarated distance field is computed to speed up reaction time to avoid collision between human operator and the robot. An automated appliance testing also involves robotized laundry loading and unloading during life cycle testing. This task involves Laundry detection, grasp pose estimation and manipulation in a container, inside the drum and during recovery grasping. A wrinkle and blob detection algorithms for grasp pose estimation are developed and grasp poses are calculated along the wrinkle and blobs to efficiently perform grasping task. By ranking the estimated laundry grasp poses according to a predefined cost function, the robotic arm attempt to grasp poses that are more comfortable from the robot kinematic side as well as collision free on the appliance side. This is achieved through appliance detection and full-model registration and collision free trajectory execution using online collision avoidance.

Untangle sustainable development goal 8 through data visualization and HCI methods

Following the approval of the 2030 Agenda for Sustainable Development in 2015, sustainability became a hotly debated topic. In order to build a better and more sustainable future by 2030, this agenda addressed several global issues, including inequality, climate change, peace, and justice, in the form of 17 Sustainable Development Goals (SDGs), that should be understood and pursued by nations, corporations, institutions, and individuals. In this thesis, we researched how to exploit and integrate Human-Computer Interaction (HCI) and Data Visualization to promote knowledge and awareness about SDG 8, which wants to encourage lasting, inclusive, and sustainable economic growth, full and productive employment, and decent work for all. In particular, we focused on three targets: green economy, sustainable tourism, employment, decent work for all, and social protection. The primary goal of this research is to determine whether HCI approaches may be used to create and validate interactive data visualization that can serve as helpful decision-making aids for specific groups and raise their knowledge of public-interest issues. To accomplish this goal, we analyzed four case studies. In the first two, we wanted to promote knowledge and awareness about green economy issues: we investigated the Human-Building Interaction inside a Smart Campus and the dematerialization process inside a University. In the third, we focused on smart tourism, investigating the relationship between locals and tourists to create meaningful connections and promote more sustainable tourism. In the fourth, we explored the industry context to highlight sustainability policies inside well-known companies. This research focuses on the hypothesis that interactive data visualization tools can make communities aware of sustainability aspects related to SDG8 and its targets. The research questions addressed are two: "how to promote awareness about SDG8 and its targets through interactive data visualizations?" and "to what extent are these interactive data visualizations effective?".

Specification, execution and verification of interaction protocols: an approach based on computational logic

Interaction protocols establish how different computational entities can interact with each other. The interaction can be finalized to the exchange of data, as in 'communication protocols', or can be oriented to achieve some result, as in 'application protocols'. Moreover, with the increasing complexity of modern distributed systems, protocols are used also to control such a complexity, and to ensure that the system as a whole evolves with certain features. However, the extensive use of protocols has raised some issues, from the language for specifying them to the several verification aspects. Computational Logic provides models, languages and tools that can be effectively adopted to address such issues: its declarative nature can be exploited for a protocol specification language, while its operational counterpart can be used to reason upon such specifications. In this thesis we propose a proof-theoretic framework, called SCIFF, together with its extensions. SCIFF is based on Abductive Logic Programming, and provides a formal specification language with a clear declarative semantics (based on abduction). The operational counterpart is given by a proof procedure, that allows to reason upon the specifications and to test the conformance of given interactions w.r.t. a defined protocol. Moreover, by suitably adapting the SCIFF Framework, we propose solutions for addressing (1) the protocol properties verification (g-SCIFF Framework), and (2) the a-priori conformance verification of peers w.r.t. the given protocol (AlLoWS Framework). We introduce also an agent based architecture, the SCIFF Agent Platform, where the same protocol specification can be used to program and to ease the implementation task of the interacting peers.

Gender equality and human development in Macedonia during transition (1991-2006)

The present thesis treats the issue of gender equality in Macedonia during the period of transition from the socialist system to the one of parliamentary democracy. The main aim is to mainstream the gender perspective in the analysis of the transitional policies through the examination of the basic citizenship rights to which citizens are entitled and by the means of the evaluation of their capabilities to exercise these rights. Gender equality, as one of the main strongholds of the concept of human development is measured through the application of nine gender relevant capabilities in a Case study conducted within selected municipalities in the country. Through the analysis of the Macedonian constitutional and legal framework and the assessment of gender based inequalities, the research questions the need for the enactment of a process of engendering of citizenship, which would integrate gender based differences, contemplate the private sphere of citizens lives and pledge participation in the political life of the country. The thesis, finally, analyses the gender equality strategy of the Macedonian government with the purpose to evaluate whether it is context based, i.e. it tackles the main fields where inequalities emerge and in this context whether it envisages a process of engendering of citizenship.

Evaluation of glycoconjugate antigens as vaccine candidates against group A Streptococcus and human immunodeficiency virus infections

This PhD thesis discusses the rationale for design and use of synthetic oligosaccharides for the development of glycoconjugate vaccines and the role of physicochemical methods in the characterization of these vaccines. The study concerns two infectious diseases that represent a serious problem for the national healthcare programs: human immunodeficiency virus (HIV) and Group A Streptococcus (GAS) infections. Both pathogens possess distinctive carbohydrate structures that have been described as suitable targets for the vaccine design. The Group A Streptococcus cell membrane polysaccharide (GAS-PS) is an attractive vaccine antigen candidate based on its conserved, constant expression pattern and the ability to confer immunoprotection in a relevant mouse model. Analysis of the immunogenic response within at-risk populations suggests an inverse correlation between high anti-GAS-PS antibody titres and GAS infection cases. Recent studies show that a chemically synthesized core polysaccharide-based antigen may represent an antigenic structural determinant of the large polysaccharide. Based on GAS-PS structural analysis, the study evaluates the potential to exploit a synthetic design approach to GAS vaccine development and compares the efficiency of synthetic antigens with the long isolated GAS polysaccharide. Synthetic GAS-PS structural analogues were specifically designed and generated to explore the impact of antigen length and terminal residue composition. For the HIV-1 glycoantigens, the dense glycan shield on the surface of the envelope protein gp120 was chosen as a target. This shield masks conserved protein epitopes and facilitates virus spread via binding to glycan receptors on susceptible host cells. The broadly neutralizing monoclonal antibody 2G12 binds a cluster of high-mannose oligosaccharides on the gp120 subunit of HIV-1 Env protein. This oligomannose epitope has been a subject to the synthetic vaccine development. The cluster nature of the 2G12 epitope suggested that multivalent antigen presentation was important to develop a carbohydrate based vaccine candidate. I describe the development of neoglycoconjugates displaying clustered HIV-1 related oligomannose carbohydrates and their immunogenic properties.

Equine and human mutual welfare: a whole subject? Critical aspects and possible strategies in equine-assisted activities and therapies

General aim of the study is equine welfare, particularly concerning different husbandry methodic and inter-specific relational factors. Specific aim is the evaluation of possible mutual (to humans and to equines) benefits and the analysis of critical factors/strength points, of human-horse relationship within Therapeutic Riding context (TR). The peculiarities of human-horse relationship (compared to the bond with “Pet”) are analyzed, concerning their socio-anthropological, psychological, psycho-dynamic distinctive characteristics. 8 European representative therapeutic riding centers (TRC) were therefore selected (on the basis of their different animals’ husbandry criteria, and of the different rehabilitative methodologies adopted). TRC were investigated through 2 different questionnaires, specifically settled to access objective/subjective animal welfare parameters; the quality of human-horse relationship; technicians’ emotional experienced. 3 Centers were further selected, and behavioral (145 hours of behavioral recording) and physiological parameters (heart rate and heart rate variability) were evaluated, aimed to access equine welfare and horses’ adaptive responses/coping (towards general environment and towards TR job). Moreover a specific “handling-task” was ideated and experimented, aimed to measure the quality of TR technicians-horses relationship. We did therefore evaluate both the individual horses’ responses and the possible differences among Centers. Data collected highlight the lack of univocal standardized methodic, concerning the general animals’ management and the specific methodologies (aimed to improve animal welfare and to empower TR efficacy). Some positive and some critical aspects were detected concerning TR personnel-horse relationship. Another experimental approach did evaluate the efficacy (concerning the mutual benefits’ empowerment) of an “ethologically-fitted” TR intervention, aimed to educate children to and through the relationship with horses. Our data evidenced that the improvement of human horse relationship, through structured educational programs for TR personnel might have important consequences both to human and equine welfare.

Semantic Service Architectures for Smart Environments

Many industries and academic institutions share the vision that an appropriate use of information originated from the environment may add value to services in multiple domains and may help humans in dealing with the growing information overload which often seems to jeopardize our life. It is also clear that information sharing and mutual understanding between software agents may impact complex processes where many actors (humans and machines) are involved, leading to relevant socioeconomic benefits. Starting from these two input, architectural and technological solutions to enable “environment-related cooperative digital services” are here explored. The proposed analysis starts from the consideration that our environment is physical space and here diversity is a major value. On the other side diversity is detrimental to common technological solutions, and it is an obstacle to mutual understanding. An appropriate environment abstraction and a shared information model are needed to provide the required levels of interoperability in our heterogeneous habitat. This thesis reviews several approaches to support environment related applications and intends to demonstrate that smart-space-based, ontology-driven, information-sharing platforms may become a flexible and powerful solution to support interoperable services in virtually any domain and even in cross-domain scenarios. It also shows that semantic technologies can be fruitfully applied not only to represent application domain knowledge. For example semantic modeling of Human-Computer Interaction may support interaction interoperability and transformation of interaction primitives into actions, and the thesis shows how smart-space-based platforms driven by an interaction ontology may enable natural ad flexible ways of accessing resources and services, e.g, with gestures. An ontology for computational flow execution has also been built to represent abstract computation, with the goal of exploring new ways of scheduling computation flows with smart-space-based semantic platforms.

Effect of different management intensities on natural and human-induced carbon fluxes in a golf course in northern Italy

Turfgrasses are ubiquitous in urban landscape and their role on carbon (C) cycle is increasing important also due to the considerable footprint related to their management practices. It is crucial to understand the mechanisms driving the C assimilation potential of these terrestrial ecosystems Several approaches have been proposed to assess C dynamics: micro-meteorological methods, small-chamber enclosure system (SC), chrono-sequence approach and various models. Natural and human-induced variables influence turfgrasses C fluxes. Species composition, environmental conditions, site characteristics, former land use and agronomic management are the most important factors considered in literature driving C sequestration potential. At the same time different approaches seem to influence C budget estimates. In order to study the effect of different management intensities on turfgrass, we estimated net ecosystem exchange (NEE) through a SC approach in a hole of a golf course in the province of Verona (Italy) for one year. The SC approach presented several advantages but also limits related to the measurement frequency, timing and duration overtime, and to the methodological errors connected to the measuring system. Daily CO2 fluxes changed according to the intensity of maintenance, likely due to different inputs and disturbances affecting biogeochemical cycles, combined also to the different leaf area index (LAI). The annual cumulative NEE decreased with the increase of the intensity of management. NEE was related to the seasonality of turfgrass, following temperatures and physiological activity. Generally on the growing season CO2 fluxes towards atmosphere exceeded C sequestered. The cumulative NEE showed a system near to a steady state for C dynamics. In the final part greenhouse gases (GHGs) emissions due to fossil fuel consumption for turfgrass upkeep were estimated, pinpointing that turfgrass may result a considerable C source. The C potential of trees and shrubs needs to be considered to obtain a complete budget.