Il presente lavoro di tesi è strutturato in tre sezioni principali. La prima, che comprende i primi due capitoli, riguarda i riferimenti per la conoscenza: al fine di definire il contesto mondiale nel quale si inserisce la tesi, vengono analizzati i dati riguardanti i disastri naturali avvenuti e quelli relativi ai possibili scenari futuri anche in relazione ai cambiamenti climatici. La seconda parte, dedicata ad approfondimenti alle scale europea e italiana, effettua nei capitoli 3-4-5 una sorta di downscaling dei primi due: la medesima struttura di analisi viene riproposta, applicata e approfondita ad una scala spaziale di maggior dettaglio, prima quella europea e successivamente quella nazionale, focalizzando l’attenzione su un particolare tipo di disastro, vale a dire le alluvioni. La terza sezione concretizza il contributo metodologico del lavoro proponendo una nuova metodologia per l’elaborazione dei piani di protezione civile comunali o intercomunali, in particolare in riferimento agli scenari di rischio idraulico, e la sua diffusione con relativa verifica applicativa. / The present study is composed of three main sections. The first, covering the first two chapters, deals with references to knowledge: in order to define the worldwide scenario to which this study is referred, data on really occurred natural disaster and on possible future events are analyzed, considering also the probable influence of the on-going climate changes. The second part, chapters 3-4-5, is a sort of downscaling to the European and Italian territory of the first two chapters’ analysis. The same methodology is detailed and implemented for the analysis of a particular event’s type: flood risk (in Europe and Italy). Third section is about the methodological contribution of the study: a new approach to civil protection planning at local level is suggested, with a particular focus on flood risk scenarios. This new civil protection planning methodology has been applied to a real context and the relative case study is presented.

The thesis deals with systems for measuring the flow of milked milk. At the beginning of the work the history of cattle breeding in the Czech Republic is described as well as the process of milking, the issue and the principles of a flow measurement. The second part deals with certification from the association ICAR and with selected flowmeters, too. The main chapter includes the principles of selected flowmeters´ operation. The selected flowmeters of milked milk, which have been certified by ICAR, are described and compared here.

Lo studio effettuato pone le sue basi sulla ricerca di materiali stradali che combinino ad elevati standard prestazionali, la riduzione dell’impatto ambientale in fase realizzativa e manutentiva. In particolare il seguente lavoro si occupa dello studio di 7 leganti modificati con polimeri ed additivati con cere. I primi infatti conferiscono alla miscela maggiore elastoplasticità, incrementandone la durabilità e la resistenza a fatica. Nei secondi la presenza del materiale paraffinico contribuisce a ridurre la viscosità del bitume, consentendo un notevole abbassamento della temperatura di produzione e stesa della miscela. Numerosi studi hanno dimostrato che le caratteristiche meccaniche della pavimentazione sono fortemente influenzate dal grado di ossidazione delle componenti organiche del bitume, ovvero dal fenomeno dell’invecchiamento o aging. Pertanto allo studio reologico del bitume, si sono affiancate prove di simulazione dell’ invecchiamento nel breve e lungo termine. In fase di ricerca sperimentale si sono analizzati i leganti modificati ed additivati secondo la teoria della viscoelasticità, simulando le reali condizioni di carico ed invecchiamento alle quali il bitume è sottoposto. Tutte le prove di caratterizzazione reologica avanzata sono state effettuate mediante l’utilizzo del DSR (Dynamic Shear Rheometer - UNI EN 14770 ) in varie configurazioni di prova e l’invecchiamento a breve termine è stato simulato mediante RTFOT (Rolling thin film oven test -UNI EN 12607-1). Si è proposto inoltre una nuova procedura di aging invecchiando il bitume alla temperatura di Twork, ovvero a quel valore della temperatura tale per cui, in fase di messa in opera, si avrà una distribuzione molecolare omogenea del modificante all’interno del bitume. / The use of modified asphalt binders in hot-mix asphalt has steadily increased over the past several decades. Modified asphalt binders currently make up over 20% of paving grade asphalt laid in all over the world, and the percentage continues to grow. In these recent years, the Warm Mix Asphalt (WMA) are spreading widely in the new road constructions and pavement rehabilitations. The main intent of WMA is to produce mixtures with similar strength, durability, and performance characteristics as traditional hot mixes using substantially reduced production temperatures. The pavement technology combine the use of polymer with the warm additive, that it will be the main core of this research. However, selecting appropriate temperatures for handling these binders has been an issue with the use of wax – polymer modified asphalt binders. The traditional method of determining appropriate mixing and compaction temperatures for an asphalt binder is based on relatively simple viscosity measurements of the asphalt. However, this method often yields excessively high temperatures for many modified binders that have caused concerns with degradation of the binder’s properties and emission problems in laboratories during preparation of samples and during production and placement of asphalt mixtures in the field.

T cells engineered with chimeric antigen receptors (CAR-T) have had breakthrough successes in cancer immunotherapy with FDA approvals. Still, the high cost of personalized CAR-T cell therapy hinders the accessibility from the public as a therapeutic option, and the lack of uniquely defined cancer-specific antigens brings the risk of life-threatening on-target, off-tumor toxicity. Changing the immune cell therapy platform to Natural Killer cells (NK cells) can be an option to develop allogenic off-the-shelf cell therapy. To reduce the on-target, off-tumor toxicity, developing an inhibitory CAR (iCAR) for cell therapy is necessary for precise logic computation and implementation of iCAR can broaden the spectrum of treatable cancers. This dissertation optimized the primary NK cell expansion platform with autologous PBMC and set robust virus transduction using pseudotyped retrovirus on the primary NK cells to use the NK cells as the cell therapy platform. I engineered iCAR candidates to suppress in response to a “safety antigen” on healthy cells, first in T cells and validated in NK cells, showing its efficacy against various versions of activating CAR (aCAR) drove killing of targets expressing activating antigen, while an inhibitory CAR (iCAR) suppressed cytotoxicity against targets expressing a safety antigen. Therapeutic immune cells equipped with the right pair of aCAR and iCAR platform will improve safety for currently validated cancer antigens and enable new therapies for previously unaddressed indications. / 2024-05-23T00:00:00Z

Enteropathogenic bacteria, such as Shigella and Salmonella, are associated with diarrheal diseases, which remain a significant cause of infant mortality worldwide. The secretion of protein effectors by the type III secretion apparatus (T3SA) is used by these pathogens to invade human cells and modulate host cell functions. First, we used RNA-Seq to analyze the differential transcriptome of Shigella flexneri when the T3SA is active or inactive. This allowed us to identify two uncharacterized genes that were temporarily named gem1 and gem3 and whose expression was regulated by MxiE and IpgC as other late substrates of the T3SA. Finally, we pursued the characterization of gem1 and gem3 at the protein level and renamed them icaT and icaR, respectively, when we found their protein products were secreted by the T3SA. Furthermore, we find homologs of icaT and icaR with a conserved MxiE box in several E. coli phylogroups. We also demonstrated that these homologous genes could be reactivated when both MxiE and IpgC were introduced in these strains. This discovery paved a new perspective on the evolution of pathogenesis into the E. coli lineage as both commensal and pathogenic strains harbored these genes. Treating infections caused by Enterobacteriaceae is becoming more challenging due to growing antibiotic resistance and no vaccines are widely available. Accordingly, the World Health Organization (WHO) recognized that we entered the "post-antibiotic era," where new antibiotics or antivirulence drugs are urgently needed, including for Shigella. The T3SA is an attractive target for antivirulence drugs, which may become alternative to classical antibiotics. Through screening 3,000 compounds, we found two novel inhibitors of the T3SA. Our data suggested that one of these candidate inhibitors, a dipyridyl-containing compound, reduces the virulence of Shigella at the transcriptional level. Indeed, the virulence inhibition occurs via the repression of the transcriptional activator VirB by the small chromosomal RNA RyhB, which is upregulated by this compound through an unknown mechanism involving the pyridyl groups. The repression of VirB induced by this molecule reduce the expression of several genes encoding parts of the T3SA. In comparison, the second compound is a quinone that seems to affect the assembly of the T3SA.

The present Ph.D. research has made important contributions towards the optimization of light packaging waste to energy alternative processes such as pyrolysis and gasification. Over more the development of an original integrated municipal solid waste scenario model that integrates the experimental results obtained in the thesis have a practical meaning suitable for large scale application. The experimental study of light packaging waste pyrolysis has brought some valuable information on: mass variation and balance (the results can be applied on a kinetic model development), activation energy, energy potential of solid and liquid by-products and chemical composition of solid and liquid pyrolysis products. The optimal temperature for light packaging waste pyrolysis (paper, cardboard and plastics) was established to be more than 500°C. The present Ph.D. research has made important contributions towards the optimization of light packaging waste to energy alternative processes such as pyrolysis and gasification. Over more the development of an original integrated municipal solid waste scenario model that integrates the experimental results obtained in the thesis have a practical meaning suitable for large scale application. The experimental study of light packaging waste pyrolysis has brought some valuable information on: mass variation and balance (the results can be applied on a kinetic model development), activation energy, energy potential of solid and liquid by-products and chemical composition of solid and liquid pyrolysis products. The optimal temperature for light packaging waste pyrolysis (paper, cardboard and plastics) was established to be more than 500°C. This experimental study leads to the optimisation of air gasification process parameters at industrial scale in a rotary reactor lab-pilot installation using light packaging waste mixtures. It was concluded that hhigher equivalent ration lowers the gas quality because of oxidization reactions at occurs at the being of the process. Without taking into account the CnHm hydrocarbons except CH4, in the present experiments the syngas low heating value will reach to its maximum at 5600 Nm3/kgpackaging waste at 900°C with an equivalent rate(ER) of 0.2. The solid residue is composed by char and ash and reaches to its maxim of 17 % from the initial feed input at 800°C and 0.2 ER. At 800 °C the gas flow rate and ER ranging between 0.2 -0.3 is 1.5-1.99 Nm3/kg . As it was expected, the gas yield increases with the increasing of temperature and gasifying agent. At 900 °C and 0.2-0.3 ER the gas flow rate registered varies between 1.58-2.1 Nm3/kg packaging waste. The novelty of the research in given by the development of a flexible and environmental friendly integrated municipal solid waste scenario model. The system model combines the selective collection rate, recycling processes, advanced mechanical sorting, solid recovered fuel production and proposes two waste to energy recovery facilities (combustion or gasification). The analyzed system complies with the EU principle of biodegradable materials minimization and is in agreement with the principle of adopting energy recovery after the implementation of material recycling options. In all cases studied, the analyzed integrated municipal solid waste system (IMSWS) minimizes the landfilling of materials and increases the energetic potential of the waste sent to energy recovery.

Dielectric elastomers (DEs) are an important class of materials, currently employed in the design and realization of electrically-driven, highly deformable actuators and devices, which find application in several fields of technology and engineering, including aerospace, biomedical and mechanical engineering. Subject to a voltage, a membrane of a soft dielectric elastomer coated by compliant electrodes reduces its thickness and expands its area, possibly deforming in-plane well beyond 100%: this principle is exploited to conceive transducers for a broad range of applications, including soft robots, adaptive optics, Braille displays and energy harvesters. Soft dielectrics undergo finite strains, and their modelling requires a formulation based on the Mechanics of Solids at large deformations. A major problem that limits the widespread diffusion of such devices in everyday technology is the high voltage required to activate large strains, because of the low dielectric permittivity of typical materials (acrylic elastomers or silicones), in the order of few unities, which governs the electromechanical coupling. Composite materials (reinforcing a soft matrix with stiff and high-permittivity particles) provide a way to overcome these limitations, as suggested by some experiments. In addition, composites can display failure modes and instabilities not displayed by homogeneous specimens that must be thoroughly investigated. Commonly, instability phenomena are seen as a serious drawback, that should be predicted and avoided. However, in some cases they can be used to activate snap-through actuation, as in the case of buckling-like or highly-deformable balloon-like actuators. Soft dielectric elastomers display electrostrictive properties (permittivity depending on the deformation) and we show how to take into account such a phenomenon within the theory of electroelasticity. Original results regard the investigation of diffuse modes (buckling like instabilities etc.), surface mode instabilities and localized modes. New (analytical) solutions for band-localization instability are provided and then it has been investigated how such instabilities are related to electrostriction. Regarding DE composites, the goal is to evaluate in detail the behaviour of two-phase rank-1 laminates in terms of different types of actuation, geometric and mechanical properties of phases, applied boundary conditions, and instabilities phenomena, in order to establish precise ranges in which the performance enhancement is effective with respect to the homogeneous counterpart.

Recent experimental results have suggested important direct implications of viscoelasticity of human cells and cell cytoskeleton dynamics on some relevant collective and at single-cell behaviors such as migration, adhesion, and morphogenesis. Other experimental studies have been performed on individual cancer and healthy cells of different types, demonstrating that the former were about 70% softer than the latter. In this thesis with the aim of characterizing — and gaining insights into — the frequency response of single-cell systems to mechanical stimuli (typically LITUS), a generalized viscoelastic paradigm which combines classical and spring-pot based (fractional derivative) models is presented. Than the modelling has been enriched considering the non-linear effect of the prestress, induced in protein filaments during cell adhesion and in the cell membrane (with a simple multiscale scheme that incorporates finite elasticity and a 3-D circus tent-like model), on the overall cell stiffness and finally determining its influence on the in-frequency response of the cell. The theoretical results have shown that the differences in stiffness — at least in principle — allow us to mechanically discriminate between tumor and normal cells: the critical frequencies associated with oscillation magnitude peaks (from tens to hundreds of kilohertz) could be helpfully utilized for targeting or ad hoc altering the functions of cancer cells. An experimental validation of the theoretical results is an ongoing work and the preparation of the experimental setup is also presented. In this thesis some first models have been presented to replicate in-vivo collective behavior of cells. Coherent angular rotation of epithelial cells has been reproduced by a cell-centered based mechanical model in which units are polarized, motile, and interact with the neighboring cells via harmonic forces. Starting from this model a continuum non-linear viscoelastic model incorporating the dynamics of liquid crystals has been studied and some preliminary numerical simulations have been performed.

Several aspects of fracture nucleation and growth in brittle porous ceramics and in thin films are investigated, through analytical, numerical modelling, and experimental validation. A mechanical experimental characterization has been developed for a porous ceramic, namely, a 3D apatite, characterised by an oriented porosity and used for biomedical applications. The ceramic is produced from wood, so that the resulting porosity evidences a multi-scale nature, a feature determining peculiar failure mechanisms and an unprecedented porosity/strength ratio. In particular, the material exhibits an exfoliation-type failure, resulting in a progressive loss in mechanical properties, occurring for compression tests parallel to the grains and for highly slender specimens. Similar cohesive-brittle behaviour is also found when the compression is applied in the direction orthogonal to the porous channels, regardless of the shape ratio of the specimen. An in-depth analysis of this response is performed by means of a phase-field model. After calibrating the model, stress-strain curves and fracturing patterns are accurately reproduced. Furthermore, the effects of multi-scale porosity on mechanical behaviour are determined. Various strategies available in the literature for evaluating the properties of porous materials are compared to the proposed phase-field approach. The results open new possibilities for the prediction and characterization of complex fracturing phenomena occurring in highly porous ceramics, so to facilitate medical applications as structural bone repair. An application of the peridynamic theory of continuum mechanics is developed to obtain a dimensional reduced formulation for the characterisation of through-thickness delamination of plates. The kinematic of the plate is carefully chosen to be composed of an absolutely continuous part and a zone where jumps in the displacements are allowed; in this way, the reduced form of the elastic bond-based peridynamic energy and the reduced Lagrangian are explicitly retrieved in a closed-form. The reduction generates a hierarchy of terms, characterizing the energy stored inside the plane element. A semi-analytical solution, obtained by means of a minimization procedure, is obtained for a test case and compared with finite element simulations. Despite the fact that the numerical model is fully three-dimensional (in other words, it is not reduced), this model leads to the same moment-curvature diagrams and nucleation/growth of the delamination surface found with the reduced formulation. Finally, the convergence of the proposed reduced model to local elastic theory at vanishing internal length is determined, so that a reduced-localized cohesive model for fracture is retrieved.

In western countries, we are now living in a period of economic prosperity. This has undermined in a certain way the “world’s balances” in terms of social, economic and well-being equilibrium. In particular, well-being grows in parallel with its side effects: it allows the population to grow, which generates a rise of the resources need, with related risk of pauperization of the planet. The two main aspects of the current world’s living system crisis are climate change and widespread poverty, even and mainly in terms of lack of housing. Until some years ago one was the cause of the other: the building sector is the most energy consumer and CO2 emitter. Anyway, thanks to the contemporary knowledge and technology, this trend is inverted: it is now quite simple, and in several countries compulsory, to realize NZEB or ZEB constructions. However, especially in growing countries, the building industry is yet too slow to meet the contemporary changes which are consistently faster and pressing. The main theme is now to explore the possibility of generating a new building system which can be fast in construction, adaptable to changes and completely fade away. It must respond either to growing needs or to change during the time. All focusing on very low energy consumption in use and to production/disposal phases.