Role of organic acids and phytonutrients as natural alternatives to antibiotics in supporting intestinal functionality

The gastrointestinal tract (GIT) represents the major portion of the body that interfaces with the external environment, with the double function of food processing and line of defense of the body. Numerous components support and regulate the barrier function of the GIT, such as tight junctions (TJs), cytokines, commensal and pathogenic microorganisms, and other systems of the organism, as the endocannabinoid system (ECS). The ECS can control several gastrointestinal functions, as well as the regulation of intestinal inflammation. Failure of the intestinal barrier function triggers an increase of the concentration of pro-inflammatory cytokines and leads to a reduction in intestinal functionality. This thesis aimed to explore the potential of natural compounds as a new alternative approach to antibiotics not only as antimicrobial, but also supporting intestinal maturation and integrity, and as immune-boosting agents. Different experiments were performed to evaluate the potential of nature-identical compounds (NICs), organic acids (OAs), and essential oils (EOs) to support and fight various stressful stimuli. In vitro, a well characterized blend of NICs and OAs were able to improve TJs and transepithelial electrical resistance (TEER) in an intestinal cell line, exerting an anti-inflammatory potential. EOs enhanced TEER and TJs mRNA levels, with a reduction of paracellular permeability, showing antioxidant and antimicrobial properties. In vivo, thymol modulates the gene expression of ECS and gut chemosensing in the GIT of piglets, where the precise localization of the cannabinoid receptors was immunohistochemically confirmed, suggesting an anti-inflammatory potential. In conclusion, natural alternative molecules represent an effective alternative to support or replace the classical pharmacological prophylaxis. These alternative molecules act not only as antimicrobial agents, but also exerted a crucial role in supporting the intestinal barrier function, preventing oxidative stress, and reducing inflammation. Moreover, thymol seems able to modulate the ECS, representing a novel frontier to support animal health and productivity.

Reexamining the Role of Incarceration and Stigma in Criminal Law

One of the ways by which the legal system has responded to different sets of problems is the blurring of the traditional boundaries of criminal law, both procedural and substantive. This study aims to explore under what conditions does this trend lead to the improvement of society's welfare by focusing on two distinguishing sanctions in criminal law, incarceration and social stigma. In analyzing how incarceration affects the incentive to an individual to violate a legal standard, we considered the crucial role of the time constraint. This aspect has not been fully explored in the literature on law and economics, especially with respect to the analysis of the beneficiality of imposing either a fine or a prison term. We observed that that when individuals are heterogeneous with respect to wealth and wage income, and when the level of activity can be considered a normal good, only the middle wage and middle income groups can be adequately deterred by a fixed fines alone regime. The existing literature only considers the case of the very poor, deemed as judgment proof. However, since imprisonment is a socially costly way to deprive individuals of their time, other alternatives may be sought such as the imposition of discriminatory monetary fine, partial incapacitation and other alternative sanctions. According to traditional legal theory, the reason why criminal law is obeyed is not mainly due to the monetary sanctions but to the stigma arising from the community’s moral condemnation that accompanies conviction or merely suspicion. However, it is not sufficiently clear whether social stigma always accompanies a criminal conviction. We addressed this issue by identifying the circumstances wherein a criminal conviction carries an additional social stigma. Our results show that social stigma is seen to accompany a conviction under the following conditions: first, when the law coincides with the society's social norms; and second, when the prohibited act provides information on an unobservable attribute or trait of an individual -- crucial in establishing or maintaining social relationships beyond mere economic relationships. Thus, even if the social planner does not impose the social sanction directly, the impact of social stigma can still be influenced by the probability of conviction and the level of the monetary fine imposed as well as the varying degree of correlation between the legal standard violated and the social traits or attributes of the individual. In this respect, criminal law serves as an institution that facilitates cognitive efficiency in the process of imposing the social sanction to the extent that the rest of society is boundedly rational and use judgment heuristics. Paradoxically, using criminal law in order to invoke stigma for the violation of a legal standard may also serve to undermine its strength. To sum, the results of our analysis reveal that the scope of criminal law is narrow both for the purposes of deterrence and cognitive efficiency. While there are certain conditions where the enforcement of criminal law may lead to an increase in social welfare, particularly with respect to incarceration and stigma, we have also identified the channels through which they could affect behavior. Since such mechanisms can be replicated in less costly ways, society should first try or seek to employ these legal institutions before turning to criminal law as a last resort.

TCAD approaches to multidimensional simulation of advanced semiconductor devices

Technology scaling increasingly emphasizes complexity and non-ideality of the electrical behavior of semiconductor devices and boosts interest on alternatives to the conventional planar MOSFET architecture. TCAD simulation tools are fundamental to the analysis and development of new technology generations. However, the increasing device complexity is reflected in an augmented dimensionality of the problems to be solved. The trade-off between accuracy and computational cost of the simulation is especially influenced by domain discretization: mesh generation is therefore one of the most critical steps and automatic approaches are sought. Moreover, the problem size is further increased by process variations, calling for a statistical representation of the single device through an ensemble of microscopically different instances. The aim of this thesis is to present multi-disciplinary approaches to handle this increasing problem dimensionality in a numerical simulation perspective. The topic of mesh generation is tackled by presenting a new Wavelet-based Adaptive Method (WAM) for the automatic refinement of 2D and 3D domain discretizations. Multiresolution techniques and efficient signal processing algorithms are exploited to increase grid resolution in the domain regions where relevant physical phenomena take place. Moreover, the grid is dynamically adapted to follow solution changes produced by bias variations and quality criteria are imposed on the produced meshes. The further dimensionality increase due to variability in extremely scaled devices is considered with reference to two increasingly critical phenomena, namely line-edge roughness (LER) and random dopant fluctuations (RD). The impact of such phenomena on FinFET devices, which represent a promising alternative to planar CMOS technology, is estimated through 2D and 3D TCAD simulations and statistical tools, taking into account matching performance of single devices as well as basic circuit blocks such as SRAMs. Several process options are compared, including resist- and spacer-defined fin patterning as well as different doping profile definitions. Combining statistical simulations with experimental data, potentialities and shortcomings of the FinFET architecture are analyzed and useful design guidelines are provided, which boost feasibility of this technology for mainstream applications in sub-45 nm generation integrated circuits.

Dietary strategies to minimize the detrimental impact of weaning on gut morphology, physiology and microbiota of piglets

Weaning is a crucial period in the management of piglets. In modern piggeries economic interest make weaning age decrease more and more and the detrimental consequences of weaning have as much importance as earlier the weaning occurs. The risk of development of post-weaning diarrhea (PWD) in piglets is high and PWD is the cause of serious economic losses in pig herds. In the past the supplementation of the feed given after weaning with growth promoters antibiotics, in order to keep PWD under control, used to be a common practice, but their usage has been banned in EU since 2006. This measure led to the investigation of alternative suitable feed supplements that would be reasonably efficient in protecting and sustaining animal health and performance. Aim of this thesis was to evaluate the effect of some different alternatives to growth-promoters antibiotics on weaning piglets and to assess if some of them could be considered as valuables options to replace auxinic in animal feeding. The study is composed by four experimental trials. The first one aims to identify mechanisms involved in the auxinic effects of antibiotics in the diets; the following three evaluate the addition butyric acid, tryptophan, and nitrate as alternative to in-feed antimicrobials. Although some results are controversial, it appears from the data presented that the alternatives to in-feed antibiotics considered may exert positive effects on some zootechnical and health parameters on piglet in the post-weaning period. Anyway, the mechanism of action and the interaction with microbiota of such additives should be investigated inside out because many effects remains poorly understood.

Sustainable inorganic Binders and Their Applications in Building Engineering: A Green Alternative to Ordinary Portland Cement

In the last decades, the building materials and construction industry has been contributing to a great extent to generate a high impact on our environment. As it has been considered one of the key areas in which to operate to significantly reduce our footprint on environment, there has been widespread belief that particular attention now has to be paid and specific measures have to be taken to limit the use of non-renewable resources.The aim of this thesis is therefore to study and evaluate sustainable alternatives to commonly used building materials, mainly based on ordinary Portland Cement, and find a supportable path to reduce CO2 emissions and promote the re-use of waste materials. More specifically, this research explores different solutions for replacing cementitious binders in distinct application fields, particularly where special and more restricting requirements are needed, such as restoration and conservation of architectural heritage. Emphasis was thus placed on aspects and implications more closely related to the concept of non-invasivity and environmental sustainability. A first part of the research was addressed to the study and development of sustainable inorganic matrices, based on lime putty, for the pre-impregnation and on-site binding of continuous carbon fiber fabrics for structural rehabilitation and heritage restoration. Moreover, with the aim to further limit the exploitation of non-renewable resources, the synthesis of chemically activated silico-aluminate materials, as metakaolin, ladle slag or fly ash, was thus successfully achieved. New sustainable binders were hence proposed as novel building materials, suitable to be used as primary component for construction and repair mortars, as bulk materials in high-temperature applications or as matrices for high-toughness fiber reinforced composites.

Emerging plant-based proteins: comparison from extraction to functional properties and food application

The increasing demand for alternatives to meat food products, which is linked to ethical and environmental reasons, highlights the necessity of using different protein sources. Plant proteins provide a valid option, thanks to the relative low costs, high availability and wide supply sources. The current process used to produce plant concentrates and isolates is the alkaline extraction followed by isoelectric precipitation. However, despite the high purity of the proteins, it presents some drawbacks. Innovative protein extraction processes are emerging, with the aim of reducing the environmental impact and the costs, as well as improving the functional properties. In this study, the traditional wet protein extraction and another simplified wet process were used to obtain protein-rich extracts out of different plants. The sources considered in the project were de-oiled sunflower and canola, chickpea, lentils, and the camelina meal, an emerging oleaginous seed interesting for its high content of omega 3. The extracts obtained from the two processes were then analysed for their capacities to hold water and fat, to form gel and a stable foam. Results highlighted strong differences concerning the protein content, yield and functionalities. The extracts obtained with the alkaline process confirmed the literature data about the four plant sources (sunflower, canola, chickpea and lentils) and allow to obtain a camelina concentrate with a protein content of 63 % and a protein recovery of 41 %. The second easiest process was not effective to obtain a protein enrichment in oleaginous sources, whereas an enrichment of 10 and 15 % was obtained in chickpea and lentils, respectively. The functional properties were also completely different: the easiest process produced protein ingredients completely water-soluble at pH 7, with a discrete foaming capacity compared to the extracts obtained with alkaline process. These characteristics could make these extracts suitable for the plant milk-analogue products.

The relation between geometry and matter in classical and quantum gravity and cosmology

The present thesis is divided into two main research areas: Classical Cosmology and (Loop) Quantum Gravity. The first part concerns cosmological models with one phantom and one scalar field, that provide the `super-accelerated' scenario not excluded by observations, thus exploring alternatives to the standard LambdaCDM scenario. The second part concerns the spinfoam approach to (Loop) Quantum Gravity, which is an attempt to provide a `sum-over-histories' formulation of gravitational quantum transition amplitudes. The research here presented focuses on the face amplitude of a generic spinfoam model for Quantum Gravity.

Diet Effects on Activation and Maturation of Feed Control over the Gastrointestinal Defence Barrier in Piglets

Weaning is an important and complex step involving many stresses that interfere deeply with feed intake, gastro-intestinal tract (GIT) development and adaptation to the weaning diet in young pigs. The health of the pig at weaning, its nutrition in the immediate post-weaning period, and the physical, microbiological and psychological environment are all factors that interact to determine food intake and subsequent growth. GIT disorders, infections and diarrhoea increase at the time of weaning, in fact pathogens such as enterotoxigenic Escherichia coli (ETEC) are major causes of mucosal damage in post-weaning disease contributing to diarrhoea in suckling and post-weaned pigs. The European ban in 2006 put on antibiotic growth promoters (AGP) has stimulated research on the mechanisms of GIT disorders and on nutritional approaches for preventing or reducing such disturbances avoiding AGPs. Concerning these aspects here are presented five studies based on the interplay among nutrition, genomic, immunity and physiology with the aim to clarify some of these problematic issues around weaning period in piglets. The first three evaluate the effects of diets threonine or tryptophan enriched on gut defence and health as possible alternatives to AGP in the gut. The fourth is focused on the possible immunological function related with the development of the stomach. The fifth is a pilot study on the gastric sensing and orexygenic signal given by fasting or re-feeding conditions. Although some results are controversial, it appears that both tryptophan and threonine supplementation in weaning diets have a preventive role in E.coli PWD and favorable effects in the gut especially in relation to ETEC susceptible genotype. While the stomach is believed as almost aseptic organ, it shows an immune activity related with the mucosal maturation. Moreover it shows an orexygenic role of both oxyntic mucosa and pyloric mucosa, and its possible relation with nutrient sensing stimuli.

Comparison of affinity chromatography supports for separation of protein

Chromatography is the most widely used technique for high-resolution separation and analysis of proteins. This technique is very useful for the purification of delicate compounds, e.g. pharmaceuticals, because it is usually performed at milder conditions than separation processes typically used by chemical industry. This thesis focuses on affinity chromatography. Chromatographic processes are traditionally performed using columns packed with porous resin. However, these supports have several limitations, including the dependence on intra-particle diffusion, a slow mass transfer mechanism, for the transport of solute molecules to the binding sites within the pores and high pressure drop through the packed bed. These limitations can be overcome by using chromatographic supports like membranes or monoliths. Dye-ligands are considered important alternatives to natural ligands. Several reactive dyes, particularly Cibacron Blue F3GA, are used as affinity ligand for protein purification. Cibacron Blue F3GA is a triazine dye that interacts specifically and reversibly with albumin. The aim of this study is to prepare dye-affinity membranes and monoliths for efficient removal of albumin and to compare the three different affinity supports: membranes and monoliths and a commercial column HiTrapTM Blue HP, produced by GE Healthcare. A comparison among the three supports was performed in terms of binding capacity at saturation (DBC100%) and dynamic binding capacity at 10% breakthrough (DBC10%) using solutions of pure BSA. The results obtained show that the CB-RC membranes and CB-Epoxy monoliths can be compared to commercial support, column HiTrapTM Blue HP, for the separation of albumin. These results encourage a further characterization of the new supports examined.

A multiparental cross population for mapping QTL for relevant agronomic traits in durum wheat (Triticum durum Desf.)

Multiparental cross designs for mapping quantitative trait loci (QTL) in crops are efficient alternatives to conventional biparental experimental populations because they exploit a broader genetic basis and higher mapping resolution. We describe the development and deployment of a multiparental recombinant inbred line (RIL) population in durum wheat (Triticum durum Desf.) obtained by crossing four elite cultivars characterized by different traits of agronomic value. A linkage map spanning 2,663 cM and including 7,594 single nucleotide polymorphisms (SNPs) was produced by genotyping 338 RILs with a wheat-dedicated 90k SNP chip. A cluster file was developed for correct allele calling in the framework of the tetraploid durum wheat genome. Based on phenotypic data collected over four field experiments, a multi-trait quantitative trait loci (QTL) analysis was carried out for 18 traits of agronomic relevance (including yield, yield-components, morpho-physiological and seed quality traits). Across environments, a total of 63 QTL were identified and characterized in terms of the four founder haplotypes. We mapped two QTL for grain yield across environments and 23 QTL for grain yield components. A novel major QTL for number of grain per spikelet/ear was mapped on chr 2A and shown to control up to 39% of phenotypic variance in this cross. Functionally different QTL alleles, in terms of direction and size of genetic effect, were distributed among the four parents. Based on the occurrence of QTL-clusters, we characterized the breeding values (in terms of effects on yield) of most of QTL for heading and maturity as well as yield component and quality QTL. This multiparental RIL population provides the wheat community with a highly informative QTL mapping resource enabling the dissection of the genetic architecture of multiple agronomic relevant traits in durum wheat.

Modelli e strumenti di supporto alla scelta informata del paziente: un argine alla medicina difensiva

L’aumento esponenziale del contenzioso medico-legale – originatosi negli USA negli anni Sessanta in proporzioni tali da far parlare di medical liability crisis, e sviluppatosi in Italia a partire dalla metà degli anni Ottanta – ha comportato e continua a comportare, unitamente ad altre conseguenze negative, il ricorso sempre più frequente dei sanitari alle pratiche di medicina difensiva, con elevatissimi costi a carico del Servizio Sanitario Nazionale dovuti alla sovrabbondanza di trattamenti e ricoveri inutili e di procedure diagnostiche invasive non necessarie, peraltro produttive di stress emotivo nei pazienti. La causa dell’aumento della litigiosità deve essere ricercata in buona parte nella relazione medico-paziente, in particolar modo con riferimento al momento informativo che precede l’acquisizione del consenso informato al trattamento clinico. In Italia, i limiti che per lo più caratterizzano gli studi riguardanti il consenso informato derivano principalmente dal fatto che essi tendono a focalizzarsi unicamente sulla componente scritta del medesimo. Il fulcro del consenso informato, invece, deve ritenersi rappresentato da una comunicazione tra sanitario e paziente relativa ad un trattamento proposto ed alle possibili alternative, alla non sottoposizione ad alcun trattamento e ai rischi e benefici di ciascuna di queste opzioni. In un tale contesto il tema della comunicazione tra il professionista e la persona assistita sta suscitando interesse poiché ci si aspetta che esso conduca a miglioramenti degli outcome dei pazienti e alla diminuzione delle denunce da parte di questi ultimi per casi di responsabilità sanitaria. La maggiore attenzione al rapporto medico - paziente ha fatto emergere il bisogno di migliorare e potenziare le abilità comunicative dei medici, in un’ottica in cui il momento comunicativo possa essere percepito dal professionista come fulcro del rapporto medico-paziente, nella prospettiva di una elaborazione di strategie di prevenzione e contrasto ai fenomeni di medicina difensiva.

Sviluppo di metodologie innovative di supporto decisionale alla progettazione basate su indicatori di prestazione

Il progetto di ricerca è finalizzato allo sviluppo di una metodologia innovativa di supporto decisionale nel processo di selezione tra alternative progettuali, basata su indicatori di prestazione. In particolare il lavoro si è focalizzato sulla definizione d’indicatori atti a supportare la decisione negli interventi di sbottigliamento di un impianto di processo. Sono stati sviluppati due indicatori, “bottleneck indicators”, che permettono di valutare la reale necessità dello sbottigliamento, individuando le cause che impediscono la produzione e lo sfruttamento delle apparecchiature. Questi sono stati validati attraverso l’applicazione all’analisi di un intervento su un impianto esistente e verificando che lo sfruttamento delle apparecchiature fosse correttamente individuato. Definita la necessità dell’intervento di sbottigliamento, è stato affrontato il problema della selezione tra alternative di processo possibili per realizzarlo. È stato applicato alla scelta un metodo basato su indicatori di sostenibilità che consente di confrontare le alternative considerando non solo il ritorno economico degli investimenti ma anche gli impatti su ambiente e sicurezza, e che è stato ulteriormente sviluppato in questa tesi. Sono stati definiti due indicatori, “area hazard indicators”, relativi alle emissioni fuggitive, per integrare questi aspetti nell’analisi della sostenibilità delle alternative. Per migliorare l’accuratezza nella quantificazione degli impatti è stato sviluppato un nuovo modello previsionale atto alla stima delle emissioni fuggitive di un impianto, basato unicamente sui dati disponibili in fase progettuale, che tiene conto delle tipologie di sorgenti emettitrici, dei loro meccanismi di perdita e della manutenzione. Validato mediante il confronto con dati sperimentali di un impianto produttivo, si è dimostrato che tale metodo è indispensabile per un corretto confronto delle alternative poiché i modelli esistenti sovrastimano eccessivamente le emissioni reali. Infine applicando gli indicatori ad un impianto esistente si è dimostrato che sono fondamentali per semplificare il processo decisionale, fornendo chiare e precise indicazioni impiegando un numero limitato di informazioni per ricavarle.

Feminist environmental humanities: intertwining theory and speculative fiction

This dissertation explores the entanglement between the visionary capacity of feminist theory to shape sustainable futures and the active contribution of feminist speculative fiction to the conceptual debate about the climate crisis. Over the last few years, increasing critical attention has been paid to ecofeminist perspectives on climate change, that see as a core cause of the climate crisis the patriarchal domination of nature, considered to go hand in hand with the oppression of women. What remains to be thoroughly scrutinised is the linkage between ecofeminist theories and other ethical stances capable of countering colonising epistemologies of mastery and dominion over nature. This dissertation intervenes in the debate about the master narrative of the Anthropocene, and about the one-dimensional perspective that often characterises its literary representations, from a feminist perspective that also aims at decolonising the imagination; it looks at literary texts that consider patriarchal domination of nature in its intersections with other injustices that play out within the Anthropocene, with a particular focus on race, colonialism, and capitalism. After an overview of the linkages between gender and climate change and between feminism and environmental humanities, it introduces the genre of climate fiction examining its main tropes. In an attempt to find alternatives to the mainstream narrative of the Anthropocene (namely to its gender-neutrality, colour-blindness, and anthropocentrism), it focuses on contemporary works of speculative fiction by four Anglophone women authors that particularly address the inequitable impacts of climate change experienced not only by women, but also by sexualised, racialised, and naturalised Others. These texts were chosen because of their specific engagement with the relationship between climate change, global capitalism, and a flat trust in techno-fixes on the one hand, and structural inequalities generated by patriarchy, racism, and intersecting systems of oppression on the other.

Role of bioactive compounds in the gastrointestinal host-pathogen interaction of poultry and swine

The better understanding of mechanisms at the basis of host-pathogen interaction can represent a valid tool to increase productivity and contain economic losses in animal production through the maintenance of intestinal homeostasis. With this project, three preliminary in vitro studies were conducted with the aim of investigating how bioactive compounds could influence mechanisms of host-pathogen interaction in poultry and swine. Different panels of nature identical compounds, medium chain fatty acids, and plant extracts were employed against strains of Salmonella Typhimurium, Brachyspira hyodysenteriae, and Salmonella Enteritidis, respectively. When bacterial field strains were tested, the comparison between natural compounds and antibiotics was examined, with the aim of evaluating the role of the substances in the antibiotic-resistance context. Results demonstrate that bioactive compounds have positive effects on the host, the pathogen, or both in different experimental conditions. Additionally, when compared to antibiotics, bioactive compounds have proven to be valid alternatives to address the phenomenon of antibiotic resistance.

Novel asymmetric geopolymer membranes for oil/water emulsions separation

In this study, it was investigated the possibility of using a geopolymeric membrane as an alternative to the expensive ceramic ones. The goal was to synthesise a low-cost membrane made entirely of geopolymer that can perform equally to commercial membranes. This study initially investigated the feasibility of preparing a microporous support suitable for microfiltration through casting and pressing techniques. Subsequently, a selective geopolymeric layer was developed and deposited on the support, with the capability to operate within the microfiltration range and to effectively separate oil from oil-water emulsions. In order to evaluate the performance, the properties of the geopolymeric supports obtained through pressing were carefully evaluated during the experimentation phase investigating the effect of varying parameters such as sodium silicate content, water content, and applied pressure. The results obtained from these evaluations showed that it is possible to produce supports with excellent porosity and highly controlled narrow pore size distributions. The most promising geopolymeric pressed support was then used for the deposition of a selective layer on its surface. Following physical characterization, it was confirmed that the resulting geopolymer membrane was suitable for use in the microfiltration range. Subsequently, the membrane was tested for its ability to separate oil from water using various emulsions prepared with different surfactants at different concentrations and pH. The results revealed that the fluxes were highly dependent on the electrostatic interaction between the membrane and the emulsion, with best results being obtained with emulsions prepared using anionic surfactants. The rejection rate of the membrane was also found to be extremely high, with values over 95%, comparable to a commercial ceramic membrane. This suggests that geopolymer membranes are suitable alternatives to ceramic membranes, offering the added benefits of lower cost and reduced environmental impact during production.