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    Injection and combustion modelling in hydrogen internal combustion engines

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    This thesis focuses on the numerical analysis of the injection, mixing, and combustion in direct injection internal combustion engines fueled by hydrogen. Most likely, the current transition towards a sustainable mobility will be achieved only through a combination of different technologies. For specific applications, such as heavyduty road transport, hydrogen-powered internal combustion engines—particularly those based on direct injection — represent a competitive powertrain solution in terms of cost and reliability compared to more innovative alternatives like fuel cells. Although internal combustion engines have been in use for over a century, the unique chemical and physical properties of hydrogen necessitate a renewed analysis of the fundamental processes governing engine operation, such as injection, fuel-air mixing, and combustion. For this reason, the first step of this thesis is the characterization of the fluid dynamics of high-pressure hydrogen direct injection into the combustion chamber. The study analyzes the fluid-dynamic structures characterizing these flows, with particular attention to the numerical setup required to accurately resolve them. With respect to the state of art, the analysis focuses on the effect of the typical combustion chamber conditions on the jet phenomenology. More specifically, an analysis is proposed by varying the cylinder pressure over time to determine the possible presence of dynamic phenomena that could alter the flow configuration compared to what is observed under constant pressure ratios. As a second step, focus has been posed on the influence of the injector exit section geometry, to determine whether specific configurations are more suitable for use in internal combustion engines. Although the injector outlet sections are primarily circular or annular, new geometries (triangular, star-shaped, rectangular, and elliptical) have been studied to understand their effect on the mixing between the jet and the surrounding environment. While some of these geometric configurations have already been analyzed in the aerospace field, their applicability in the automotive sector has been tested in this thesis work. Significant differences have been observed in the shock and expansion system characterizing these flows, for which a detailed explanation has been provided. Subsequently, the analysis has been extended to the design space of key variables affecting the mixing process, such as the injection pressure, timing, and nozzle geometry. The goal has been to extend the engine operability under increasingly lean mixtures compared to the current state of the art. More specifically, focus has been placed on mixtures featured by an equivalence ratio of 0.25, which help to reduce wall heat losses while limiting nitrogen oxide emissions. It has been demonstrated that the mixture stratification under these conditions is the key to increasing the combustion process speed. In particular, multi-injection strategies have been tested, showing the potential to optimize the combustion speed and NOx emissions. Finally, in an effort to improve internal combustion engine modeling, a procedure has been developed to account for the effects of thermodiffusive instabilities in hydrogen flames within the framework of the G-equation combustion model. Preliminary results show the potential to effectively capture pressure trends with a single preliminary calibration process regarding the interaction between the flame front and the in-cylinder turbulence

    DEVELOPMENT OF AN INTEGRATED SYSTEM BIOLOGY MODEL FOR PREDICTING MIXTURES OF CHEMICALS ACTING ON THE SAME PATHWAY

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    Exposure of the embryo to environmental chemicals (pesticides, air and water pollutants) can result in congenital malformations or developmental defects such as oro-facial cleftings. Unfortunately, the human embryo is not usually exposed to a single substance, but to many substances simultaneously. Despite the efforts in elucidating mechanism of action (MoA) of substances that perturb the normal embryonic development, only a small part of involved pathways have been understood to date (Giavini and Menegola, 2004). This is why, evaluating the toxicity of mixtures of multiple chemicals is one of the major objectives of today’s toxicology despite the effect of exposure to a mixture is still difficult to understand. To arrive in the future to the creation of a realistic overall picture of human exposure to mixtures, the development of integrated approaches between in vitro and in silico techniques and computational systems biology, able to predict the effects of mixtures starting from the concentrations of their individual components, will be essential. Recent studies suggest that the similarity of molecular initiating events (MIEs) is not an essential requirement to induce additive effects, because mixtures composed of chemicals with different MIE can exhibit mixture effects too, probably acting on the same biological pathway and contributing to the same adverse outcome (EFSA, 2013). This is in recognition of emerging evidence that biological effects can be similar, although the molecular details of toxicological mechanisms may profoundly differ in many respects (Kortenkamp, 2007). Considering the previously reported data, this could be the case of embryonic co-exposure to fluconazole (FLUCO) and ethanol (Eth). Both, in fact, lead to the same adverse outcome (AO), craniofacial malformations, both after in utero and in vitro exposure. The two molecules are able to induce cranio-facial defects (in embryos visible as cranio-facial abnormalities), probably acting on the same Adverse Outcome Pathway (AOP) altering, with different MIEs, the biological event cascade regulated by the morphogen retinoic acid (RA). The specific aim of this PhD project was to investigate this hypothesis through the development of an in silico model, useful to simulate and predict the effects on embryo development after co-exposure to substances with independent MoAs but acting on the same biological pathway and potentially contributing to the same adverse outcome (cranio-facial malformations). The in silico model was based on experimental data and validated by in vitro experiments. For this purpose, the project was divided into three parts. In the first part, we evaluated the effects of the molecules on post-implantation rat embryos cultures, using the in vitro technique WEC (Whole Embryo Culture). Embryos were cultured in presence of increasing concentration of RA (0.025-0.0375-0.05-0.125-0.25 μM), to increasing concentrations of Eth (17-42.5-85-127 mM), to increasing concentrations of FLUCO (62.5-125-250-500 μM). Specific and concentration related abnormalities at the level of the branchial arches (reductions or fusions) were observed after exposure to single Eth or FLUCO and were comparable to those elicited by RA. These results suggest a common AO for Eth, FLUCO and RA. Embryos were then co-exposed to binary mixtures of FLUCO and Eth. To better characterize the contribution of each component to the observed effects, the “fixed + moving” approach was applied: embryos were exposed to the no effect concentration (NOAEL) of one chemical (“fixed”) and increasing concentrations of the other chemical (“moving”). A significant enhancement of teratogenic effects was observed after co-exposure to FLUCO and Eth in comparison to the single exposure. The mixture between the two NOAELs was effective too, inducing almost 40% of branchial arch abnormalities. These data suggest the presence of a cumulative effect in mixture, probably due to the capability of both molecules to perturb RA endogenous concentrations in specific tissues (the precursors of cranio-facial skeletal tissues, originated in the embryonic hindbrain). This theory could be explained considering the ability of Eth to induce alcohol-dehydrogenases (including ADH7, the embryonic enzyme involved in RA synthesis) and the inhibitory effects of FLUCO on cytochromes p450 (including CYP26, involved in embryonic RA degradation). In the second part of the project, we evaluated these hypothetical mechanisms inducing the Eth-FLUCO mixture effects through the development of an in silico tool, able to simulate both the formation of the physiological RA gradient in the rat embryo hindbrain and its perturbation after exposure to FLUCO, Eth and to their binary mixtures. The obtained system biology model, developed using an integrated approach combining mathematical modelling, molecular docking and in vitro experiments, seems to be reasonably predictive for the mixture’s effects, confirming the accuracy of the hypothesized pathogenic pathway. Experimental data and model predictions, in fact, showed a promising agreement. The model, in spite of its limitations, could have many potential mechanistic or predictive applications for the study of risk assessment. However, since the model is based on experimental data obtained in mammals, the last part of the project was aimed to evaluate alternative animal models. In the third part of the project, the evaluation of the effects after co-exposure to FLUCO and Eth were performed using the ascidian Ciona intestinalis embryo model as a new alternative teratological screening test (AET, Ascidian Embryo Teratogenicity assay). An ascidian species was selected because Ascidiacea represent the sister group of Vertebrates. For this purpose, C. intestinalis embryos were exposed to Eth alone (1.7-8.5-17-42.5-85 mM) to FLUCO alone (7.8-15.75-31.5-250 μM), or co-exposed to binary mixtures of FLUCO and Eth until the larval stage, applying the fix + moving protocol. Specific and concentration related abnormalities at the level of the anterior structures were elicited by Eth or FLUCO, and were comparable to those described in literature after RA exposure. A significant enhancement of the general teratogenicity was observed after co-exposure to FLUCO and Eth in comparison to the single exposure, suggesting the presence of a mixture effect induced by FLUCO and Eth also in this model. These results, similar to those observed in the WEC model, encourage the use of AET as a complementary alternative method for embryotoxicity studies on mixtures. The possibility to translate data obtained in this model in our in silico model is still to evaluate. In conclusion, our data suggest that: 1. the integrated use of data from in vitro and in silico approaches used in this study support the hypothesis that embryonic exposure to FLUCO and Eth can lead to the same AO (craniofacial abnormalities) acting with different MIEs but both converging on the same AOP by altering the RA production (Eth) and the RA catabolism (FLUCO); 2. the hypothesis that substances with different MoAs but acting on the same pathway could produce an additive effect also at concentrations considered not effective is supported; 3. the obtained results highlight the potential additive effect that could occur after exposure to azoles and ethanol, suggesting a precautionary position in alcohol consumption during azoles exposure in pregnancy. The overall view of the obtained results support the need of a cumulative risk assessment not only for chemicals grouped on the base of similarities in chemical structure or derived from mechanistic considerations but also for chemicals differently acting on the same biological pathway

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    Mixture effect of two antifungal triazoles (triadimefon and cyproconazole) in rat and Amphibian embryos cultured in vitro

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    The present work aims to evaluate the teratogenic potential of two triazole-derived fungicides (triadimefon, FON, cyproconazole, CYPRO) alone, as well as their action in a mixed solution on Amphibian (Xenopus laevis) and rat embryos cultured in vitro. On the basis of the morphological and molecular interclasses similarities at the phylotypic stage, low vertebrate animal models have been proposed as alternative to mammals in assessing the developmental toxicity of xenobiotics. Triazole derivatives represent a large class of molecules with antifungal properties, used in agriculture and human-veterinary therapy. Experimental studies indicate all the tested triazoles as teratogenic in rodents, rabbits, amphibians and tunicates, and neurulation as the most sensitive period for inducing craniofacial defects thus affecting the organization of embryonic transient structures (branchial arches). Rat embryos were exposed during the whole culture period (from early neurulation till phylotypic stage) to 7.8–250Mof two agrochemical triazoles (FON and CYPRO) alone, or to their mixture (MIX1: FON 7.8M plus CYPRO 7.8M). At the end of the culture period embryos were morphologically examined and immunostained to evaluate neural crest cell migration. X. laevis embryos were exposed during early neurulation stages to FON and CYPRO alone (3.9-250M), to MIX1, and to MIX2 (FON 3.9M plus CYPRO 3.9M). At the end of the exposures, embryos were washed and allowed to reach the phylotypic stage or the larval stage 47 to evaluate neural crest cell migration and craniofacial morphology. The obtained results confirmFONand CYPRO as teratogenic and showed a clear mixture effect in both species. This suggests that the teratogenic mechanism is common for the two molecules and that it is able to act in different Vertebrate species, indicating X. laevis as an adequate alternative animal model for teratogenic screening of mixtures obtained from molecules of this chemical class
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