A step forwards in immunomodulation and immunetolerance knowledge. HLA-G expression in co-cultures of peripheral blood mononuclear cells and stem cells after in vitro NGAL stimulation

NGAL (Neutrophil Gelatinase-associated Lipocalin ) is a protein of lipocalin superfamily. Recent literature focused on its biomarkers function in several pathological condition (acute and chronic kidney damage, autoimmune disease, malignancy). NGAL biological role is not well elucidated. Several are the demonstration of its bacteriostatic role. Recent papers have indeed highlight NGAL role in NFkB modulation. The aim of this study is to understand whether NGAL may exert a role in the activation (modulation) of T cell response through the regulation of HLA-G complex, a mediator of tolerance. From 8 healthy donors we obtained peripheral blood mononuclear cells (PBMCs) and we isolated by centrifugation on a Ficoll gradient. Cells were then treated with four concentrations of NGAL (40-320 ng/ml) with or without iron. We performed flow cytometry analysis and ELISA test. NGAL increased the HLA-G expression on CD4+ T cells, with an increasing corresponding to the dose. Iron effect is not of unique interpretation. NGAL adiction affects regulatory T cells increasing in vitro expansion of CD4+ CD25+ FoxP3+ cells. Neutralizing antibody against NGAL decreased HLA-G expression and reduced significantly CD4+ CD25+ FoxP3+ cells percentage. In conclusion, we provided in vitro evidence of NGAL involvement in cellular immunity. The potential role of NGAL as an immunomodulatory molecule has been evaluated: it has been shown that NGAL plays a pivotal role in the induction of immune tolerance up regulating HLA-G and T regulatory cells expression in healthy donors. As potential future scenario we highlight the in vivo role of NGAL in immunology and immunomodulation, and its possible relationship with immunosuppressive therapy efficacy, tolerance induction in transplant patients, and/or in other immunological disorders.

Methods for objective and interpretative evaluation of function and motor control: gait in perturbed condition and in the aquatic therapy

Gait analysis allows to characterize motor function, highlighting deviations from normal motor behavior related to an underlying pathology. The widespread use of wearable inertial sensors has opened the way to the evaluation of ecological gait, and a variety of methodological approaches and algorithms have been proposed for the characterization of gait from inertial measures (e.g. for temporal parameters, motor stability and variability, specific pathological alterations). However, no comparative analysis of their performance (i.e. accuracy, repeatability) was available yet, in particular, analysing how this performance is affected by extrinsic (i.e. sensor location, computational approach, analysed variable, testing environmental constraints) and intrinsic (i.e. functional alterations resulting from pathology) factors. The aim of the present project was to comparatively analyze the influence of intrinsic and extrinsic factors on the performance of the numerous algorithms proposed in the literature for the quantification of specific characteristics (i.e. timing, variability/stability) and alterations (i.e. freezing) of gait. Considering extrinsic factors, the influence of sensor location, analyzed variable, and computational approach on the performance of a selection of gait segmentation algorithms from a literature review was analysed in different environmental conditions (e.g. solid ground, sand, in water). Moreover, the influence of altered environmental conditions (i.e. in water) was analyzed as referred to the minimum number of stride necessary to obtain reliable estimates of gait variability and stability metrics, integrating what already available in the literature for over ground gait in healthy subjects. Considering intrinsic factors, the influence of specific pathological conditions (i.e. Parkinson’s Disease) was analyzed as affecting the performance of segmentation algorithms, with and without freezing. Finally, the analysis of the performance of algorithms for the detection of gait freezing showed how results depend on the domain of implementation and IMU position.

On the role of Computational Logic in Data Science: representing, learning, reasoning, and explaining knowledge

In this thesis we discuss in what ways computational logic (CL) and data science (DS) can jointly contribute to the management of knowledge within the scope of modern and future artificial intelligence (AI), and how technically-sound software technologies can be realised along the path. An agent-oriented mindset permeates the whole discussion, by stressing pivotal role of autonomous agents in exploiting both means to reach higher degrees of intelligence. Accordingly, the goals of this thesis are manifold. First, we elicit the analogies and differences among CL and DS, hence looking for possible synergies and complementarities along 4 major knowledge-related dimensions, namely representation, acquisition (a.k.a. learning), inference (a.k.a. reasoning), and explanation. In this regard, we propose a conceptual framework through which bridges these disciplines can be described and designed. We then survey the current state of the art of AI technologies, w.r.t. their capability to support bridging CL and DS in practice. After detecting lacks and opportunities, we propose the notion of logic ecosystem as the new conceptual, architectural, and technological solution supporting the incremental integration of symbolic and sub-symbolic AI. Finally, we discuss how our notion of logic ecosys- tem can be reified into actual software technology and extended towards many DS-related directions.

Innovation Diffusion and Biostimulant knowledge in Moroccan agriculture

Our study focused on Morocco investigating the dissemination of PBs amongst farmers belonging to the first pillar of the GMP, located in the Fès-Meknès region. As well as to assess how innovation adoption is influenced by the network of relationships that various farmers are involved in. We adopted an “ego network” approach to identify the primary stakeholders responsible for the diffusion of PBs. We collected data through “face-to-face” interviews with 80 farmers in April and May 2021. The data were processed with the aim of: 1) analysing the total number of main and specific topics discussed between egos and egos’ alters regarding the variation of some egos attributes; 2) analysing egos’ network characteristics using E-Net software, and 3) identifying the significant variables that influence farmers to access knowledge, use and reuse of PBs a Binary Logistic Regression (LR) was applied. The first result disclosed that the main PBs topics discussed were technical positioning, the need to use PBs, knowledge of PBs, and organic PBs. We noted that farmers have specific features: they have a high school diploma and a bachelor's degree; they are specialised in fruits and cereals farming, and they are managers and members of a professional organisation. The second result showed results of SNA: 1) PBs seem to become generally a common argument for farmers who have already exchanged fertiliser information with their alters; 2) we disclosed a moderate heterogeneity in the networks, farmers have access to information mainly from acquaintances and professionals, and 3) we revealed that networks have a relatively low density and alters are not tightly connected to each other. Farmers have a brokerage position in the networks controlling the flow of information about the PBs. LR revealed that both the farmers’ attributes and the networks’ characteristics influence growers to know, use and reuse PBs.

Knowledge Flows and Networks: the Interplay between Local and Global Linkages within Bangalore IT Cluster

This doctoral work gains deeper insight into the dynamics of knowledge flows within and across clusters, unfolding their features, directions and strategic implications. Alliances, networks and personnel mobility are acknowledged as the three main channels of inter-firm knowledge flows, thus offering three heterogeneous measures to analyze the phenomenon. The interplay between the three channels and the richness of available research methods, has allowed for the elaboration of three different papers and perspectives. The common empirical setting is the IT cluster in Bangalore, for its distinguished features as a high-tech cluster and for its steady yearly two-digit growth around the service-based business model. The first paper deploys both a firm-level and a tie-level analysis, exploring the cases of 4 domestic companies and of 2 MNCs active the cluster, according to a cluster-based perspective. The distinction between business-domain knowledge and technical knowledge emerges from the qualitative evidence, further confirmed by quantitative analyses at tie-level. At firm-level, the specialization degree seems to be influencing the kind of knowledge shared, while at tie-level both the frequency of interaction and the governance mode prove to determine differences in the distribution of knowledge flows. The second paper zooms out and considers the inter-firm networks; particularly focusing on the role of cluster boundary, internal and external networks are analyzed, in their size, long-term orientation and exploration degree. The research method is purely qualitative and allows for the observation of the evolving strategic role of internal network: from exploitation-based to exploration-based. Moreover, a causal pattern is emphasized, linking the evolution and features of the external network to the evolution and features of internal network. The final paper addresses the softer and more micro-level side of knowledge flows: personnel mobility. A social capital perspective is here developed, which considers both employees’ acquisition and employees’ loss as building inter-firm ties, thus enhancing company’s overall social capital. Negative binomial regression analyses at dyad-level test the significant impact of cluster affiliation (cluster firms vs non-cluster firms), industry affiliation (IT firms vs non-IT fims) and foreign affiliation (MNCs vs domestic firms) in shaping the uneven distribution of personnel mobility, and thus of knowledge flows, among companies.

Structure-Property Relationships and Charge Transport Modeling of Organic Molecular Materials

From the perspective of a new-generation opto-electronic technology based on organic semiconductors, a major objective is to achieve a deep and detailed knowledge of the structure-property relationships, in order to optimize the electronic, optical, and charge transport properties by tuning the chemical-physical characteristics of the compounds. The purpose of this dissertation is to contribute to such understanding, through suitable theoretical and computational studies. Precisely, the structural, electronic, optical, and charge transport characteristics of several promising organic materials recently synthesized are investigated by means of an integrated approach encompassing quantum-chemical calculations, molecular dynamics and kinetic Monte Carlo simulations. Particular care is addressed to the rationalization of optical and charge transport properties in terms of both intra- and intermolecular features. Moreover, a considerable part of this project involves the development of a home-made set of procedures and parts of software code required to assist the modeling of charge transport properties in the framework of the non-adiabatic hopping mechanism applied to organic crystalline materials. As a first part of my investigations, I mainly discuss the optical, electronic, and structural properties of several core-extended rylene derivatives, which can be regarded to as model compounds for graphene nanoribbons. Two families have been studied, consisting in bay-linked perylene bisimide oligomers and N-annulated rylenes. Beside rylene derivatives, my studies also concerned electronic and spectroscopic properties of tetracene diimides, quinoidal oligothiophenes, and oxygen doped picene. As an example of device application, I studied the structural characteristics governing the efficiency of resistive molecular memories based on a derivative of benzoquinone. Finally, as a second part of my investigations, I concentrate on the charge transport properties of perylene bisimides derivatives. Precisely, a comprehensive study of the structural and thermal effects on the charge transport of several core-twisted chlorinated and fluoro-alkylated perylene bisimide n-type semiconductors is presented.

Modeling systems and vis/NIR device to improve peach and nectarine pre and post-harvest fruit maturity management

During the last decade peach and nectarine fruit have lost considerable market share, due to increased consumer dissatisfaction with quality at retail markets. This is mainly due to harvesting of too immature fruit and high ripening heterogeneity. The main problem is that the traditional used maturity indexes are not able to objectively detect fruit maturity stage, neither the variability present in the field, leading to a difficult post-harvest management of the product and to high fruit losses. To assess more precisely the fruit ripening other techniques and devices can be used. Recently, a new non-destructive maturity index, based on the vis-NIR technology, the Index of Absorbance Difference (IAD), that correlates with fruit degreening and ethylene production, was introduced and the IAD was used to study peach and nectarine fruit ripening from the “field to the fork”. In order to choose the best techniques to improve fruit quality, a detailed description of the tree structure, of fruit distribution and ripening evolution on the tree was faced. More in details, an architectural model (PlantToon®) was used to design the tree structure and the IAD was applied to characterize the maturity stage of each fruit. Their combined use provided an objective and precise evaluation of the fruit ripening variability, related to different training systems, crop load, fruit exposure and internal temperature. Based on simple field assessment of fruit maturity (as IAD) and growth, a model for an early prediction of harvest date and yield, was developed and validated. The relationship between the non-destructive maturity IAD, and the fruit shelf-life, was also confirmed. Finally the obtained results were validated by consumer test: the fruit sorted in different maturity classes obtained a different consumer acceptance. The improved knowledge, leaded to an innovative management of peach and nectarine fruit, from “field to market”.

Experimental and Numerical Analysis of Gas Forced Convection through Microtubes and Micro Heat Exchangers

The last decade has witnessed very fast development in microfabrication technologies. The increasing industrial applications of microfluidic systems call for more intensive and systematic knowledge on this newly emerging field. Especially for gaseous flow and heat transfer at microscale, the applicability of conventional theories developed at macro scale is not yet completely validated; this is mainly due to scarce experimental data available in literature for gas flows. The objective of this thesis is to investigate these unclear elements by analyzing forced convection for gaseous flows through microtubes and micro heat exchangers. Experimental tests have been performed with microtubes having various inner diameters, namely 750 m, 510 m and 170 m, over a wide range of Reynolds number covering the laminar region, the transitional zone and also the onset region of the turbulent regime. The results show that conventional theory is able to predict the flow friction factor when flow compressibility does not appear and the effect of fluid temperature-dependent properties is insignificant. A double-layered microchannel heat exchanger has been designed in order to study experimentally the efficiency of a gas-to-gas micro heat exchanger. This microdevice contains 133 parallel microchannels machined into polished PEEK plates for both the hot side and the cold side. The microchannels are 200 µm high, 200 µm wide and 39.8 mm long. The design of the micro device has been made in order to be able to test different materials as partition foil with flexible thickness. Experimental tests have been carried out for five different partition foils, with various mass flow rates and flow configurations. The experimental results indicate that the thermal performance of the countercurrent and cross flow micro heat exchanger can be strongly influenced by axial conduction in the partition foil separating the hot gas flow and cold gas flow.

A spectroscopic and photometric study of stellar populations in a sample of clusters in the Magellanic Clouds

This Ph.D. Thesis has been carried out in the framework of a long-term and large project devoted to describe the main photometric, chemical, evolutionary and integrated properties of a representative sample of Large and Small Magellanic Cloud (LMC and SMC respectively) clusters. The globular clusters system of these two Irregular galaxies provides a rich resource for investigating stellar and chemical evolution and to obtain a detailed view of the star formation history and chemical enrichment of the Clouds. The results discussed here are based on the analysis of high-resolution photometric and spectroscopic datasets obtained by using the last generation of imagers and spectrographs. The principal aims of this project are summarized as follows: • The study of the AGB and RGB sequences in a sample of MC clusters, through the analysis of a wide near-infrared photometric database, including 33 Magellanic globulars obtained in three observing runs with the near-infrared camera SOFI@NTT (ESO, La Silla). • The study of the chemical properties of a sample of MCs clusters, by using optical and near-infrared high-resolution spectra. 3 observing runs have been secured to our group to observe 9 LMC clusters (with ages between 100 Myr and 13 Gyr) with the optical high-resolution spectrograph FLAMES@VLT (ESO, Paranal) and 4 very young (<30 Myr) clusters (3 in the LMC and 1 in the SMC) with the near-infrared high-resolution spectrograph CRIRES@VLT. • The study of the photometric properties of the main evolutive sequences in optical Color- Magnitude Diagrams (CMD) obtained by using HST archive data, with the final aim of dating several clusters via the comparison between the observed CMDs and theoretical isochrones. The determination of the age of a stellar population requires an accurate measure of the Main Sequence (MS) Turn-Off (TO) luminosity and the knowledge of the distance modulus, reddening and overall metallicity. For this purpose, we limited the study of the age just to the clusters already observed with high-resolution spectroscopy, in order to date only clusters with accurate estimates of the overall metallicity.