1731 research outputs found
Sort by
Non è la fine del mondo. Lalande, le comete e la comunicazione del rischio nel Settecento.
No full textNell'aprile del 1773, Parigi fu scossa dal timore che una cometa provocasse un disastroso cataclisma. All'origine del clamore, il "Mémoire sur les comètes" dell'astronomo Lalande (Bourg-en-Bresse 1732-Paris, 1807), che aveva sostenuto la non impossibilità fisica e matematica di uno scontro/incontro tra Terra e comete
La mente dei civili. Storia e storie da un manicomio di confine (Pergine Valsugana 1909-1924)
No full textLa tesi esamina tutte le cartelle cliniche prodotte tra il 1909 e il 1924, nel manicomio di Pergine Valsugana. Lo scopo dell'elaborato è l'analisi delle conseguenze psicofisiche lasciate dalla Grande Guerra sulla popolazione, sia civile che militare
Behaviour and modelling of the inelastic response of concrete and steel-concrete infrastructures subjected to low-cycle fatigue
Get PDFNowadays, infrastructures are of strategical importance for allowing communication between countries. Owing to its usefulness, the design and the maintenance of bridges, streets and tunnels, which represent the network, become a fundamental issue. In order to investigate the behaviour of infrastructures under different loads, such as gravity, seismic phenomena, thermal differences, and so on, appears essential a comprehensive experimental campaign on scaled and full-scale specimens. In particular, in order to guarantee the safety of citizens, the seismic response of infrastructures under an earthquake requires a careful evaluation of the level of damage of structural elements.
In this thesis, typical case studies are considered, such as a concrete tunnel lining and a composite steel-concrete bridge. In the first part of the thesis, a typical concrete tunnel lining is analysed. In order to investigate the inelastic behaviour of a concrete circular tunnel, several tests were performed. In greater detail, the best Fiber Bragg Grating (FBG) package configuration was obtained by means of monotonic and cyclic tests on substructures. Based on these results, the resulting suitable configuration in a full-scale tunnel test was used to measure deformations with high accuracy. Cyclic test on the full-scale tunnel provided data on the damage of reinforcing concrete and the developing of plastic hinges. With the aim of providing information on the structural safety of a tunnel after an earthquake, a damage index was calculated. In this respect, a nonlinear fiber F.E. model in the OpenSEES environmental was developed. This model calculated the stress in terms of bending moment in concrete sections with the use of experimental curvatures measured by FBGs system. Finally, the damage evolution in the concrete tunnel was reported and commented. In the second part of this thesis, a composite steel-concrete short-medium span bridge is treated. The innovation was the application of the PEER Performance-Based Earthquake Engineering (PBEE) to this type of bridge. Moreover, the use of the Hot-rolled (HRS) steel to manufacture I-girder beams has become an innovation in civil infrastructures in Europe, as much as the use of transversal concrete cross-beams (CCBs) to connect spans. With reference to the hazard selected, a suitable case study was chosen. With the aim of understanding the most critical and stressed parts of the case study, preliminary elastic shell and stick models were developed. After the identification of interesting parts, half-scale subassembly specimens were designed and built. Several quasi-static tests, both monotonic and cyclic, were carried out with the objective of exploring global and local mechanisms in the section owing to low-cycle fatigue phenomena. To detect damage in the connection detail, a refined F.E. model in ABAQUS was developed. Fragility curve parameters of the damage's interest quantities were obtained by fitting experimental and numerical data by means of the Maximum Likelihood Estimation method. The results and the numerical model could be ready for the application of the Performance-Based Earthquake Engineering tool, in which decision variables, such as repair costs, downtime, human life loss and lane closures, were taken into consideration in order to increase the confidence in the design for both engineer and owner's viewpoint
Novel multi-modal wideband vibrations MEMS energy harvesting concepts for self-powered Internet of Things (IoT) applications, with focus on converterâs size and power scalability
No full textThis doctorate thesis is focused on the design, fabrication and characterization of Micro Electro Mechanical System (MEMS) Vibrational Energy Harvesters (VEHs). The targeted field of application of such devices is the emerging Internet of Things (IoT), in particular for Ultra Low Power (ULP) autonomous applications. In order to realize the ubiquitous paradigm remote and distributed nodes have to be small and in high number. The power requirement of such nodes is generally satisfied by means of batteries, which require periodic replacement and so are not desirable in an autonomous system. To overcome this limitation devices able to harvest energy from the surrounding environment have been investigated. Among the different sources of energy that could be harvested, the vibrational one results promising due to its high power density and its spreading in most environments of interest. The devices developed convert the vibrational energy scattered in the environment into electrical energy by means of a piezoelectric material. The thesis presents studies on both the mechanical and the electric design of a MEMS piezoelectric VEH, with particular attention on multi-modal design. The thesis presents a novel multi-modal device able to extract energy from multiple resonances in a wider bandwidth. Such a design presents two enabling features for IoT application, a wider working band and the compactness, making it more attractive with respect to cantilever like devices
On Individual Decision Making and Responsibility for Others
No full textIndividuals' concerns for others have been the focus of many experimental investigations since the first appearance of the dictator game, which pointed out that, when people have to allocate resources and determine their own and others' payoffs, they decide accordingly to some well-defined distributional preferences. These, depending on the decisional setting and on individuals, are able to generate discrepancies between decisions that only affect the decision maker and choices that have consequences on others' payoffs. Starting from these considerations, the three studies presented in this thesis have the aim to picture the state of the art in the literature related to decision making and responsibility for others. Specifically, Chapter 2 presents an overview of past contributions, providing an analysis of three different experimental literatures: dictator games, delegated decision making under risk, and leadership in cooperation; the last two are then experimentally investigated more in details in the following chapters. Specifically, Chapter 3 focuses on investment in risk protection when risk is borne either by the decision maker or by another individual. In addition to this, the analysis manipulates who is the subject providing the resources to buy risk protection. Laboratory observations are assessed against behavioral predictions obtained from a linear model for social preferences to test its predictive power in this domain. Chapter 4 drives the attention to the effect of leadership in a public good experiment. Leaders take part to a public good game, aware of the fact that every decision they make directly affects their followers, who can be either passive players or have the opportunity to send short messages to their leader. This experimental setting allows to observe how people decide for themselves and others when involved in strategic interaction
Fractional diffusion: biological models and nonlinear problems driven by the s-power of the Laplacian.
No full textIn the classical theory, the fractional diffusion is ruled by two different types of fractional Laplacians. Formerly known since 60s, the spectral fractional Laplacian had an important development in the recent mathematical study with the initial contributes of L. Caffarelli, L. Silvestre and X. Cabré, X.Tan. The integral version of the fractional Laplacian, recently discussed by M. Fukushima, Y. Oshima, M Takeda, and Song, Vondracek, is considered in a
semilinear elliptic problem in presence of a general logistic function and an indefinite weight.
In particular we look for a multiplicity result for the associated Dirichlet problem. In the second part, starting from the classical works of T.Hillen and G. Othmer and taking the Generalized velocity jump processes presented in a recent work of J.T.King, we obtain the fractional diffusion as limit of this last processes using the technique used in another recent work of Mellet, without the classical Hilbert or Cattaneo approximation's methods
Streamflow Generation in alpine Catchments: The role of hydrological and geochemical information
No full textHeadwaters in Alpine regions represent the large majority of streams in natural or nearly natural conditions, which provide essential ecosystem services. These catchments are particularly sensitive to temperature changes and may suer significant changes because of climate variations. Thus, identifying the main mechanisms controlling streamflow generation and understanding the nature and variability of streamflow in Alpine streams, represent a very important contribution towards a better understanding of these complex systems. Among the multiplicity of streamflow sources (e.g., rain, snow-melt, ice-melt and groundwater), in particular snow and ice-melt play a fundamental role on the hydrological cycle of Alpine catchments and strongly affect streamflow regime. Despite several research efforts over the past decades focused on understanding the complex dynamics of the hydrological processes that characterize these environments, there is still much to disclose. Hence, the interpretation of streamflow sources can become very difficult with water discharge as the sole observed variable. The previous calls for the use of alternative data sources and methods for data analysis and visualization.
This doctoral thesis aimed to contribute with new insights into the multifaceted aspects of streamflow generation in Alpine river catchments, exploring the different roles played by hydrological and geochemical information and the use of several techniques, such us tracer-based analysis, continuous wavelet transform, wavelet coherence, cross-correlation and Hovmöller diagrams; in order to investigate the mechanisms controlling streamflow generation on real case studies at different temporal scales. Hence, the present thesis is based on four main elements.
In the first part of this work we show how tracer data (i.e., electrical conductivity and stable isotopes of stream water) can be used to separate the contribution of pre-event and event waters applying a two-component mixing analysis on four single rainfall events identied in the Vermigliana catchment, North-Eastern Italian Alps. The separation of streamflow into two different components allowed us to improve the conceptual model of the catchment introducing constraints that are impossible to envision counting only on streamflow measurements. Moreover, we show that the relative contribution of event water with respect to pre-event water does not change only according to the magnitude of the precipitation event and on the variations in air temperature, but it also depends on the presence and thickness of the snowpack present during the event.
Second, we explored the correlation between stream water electrical conductivity (EC) and water discharge (Q) using continuous records collected during two melting periods of the Vermigliana catchment. The analysis of the hysteresis relating EC and Q at the annual scale evidenced the limitations of the use of EC measurements as a proxy of Q in these type of catchments. In addition, the combined analysis of the correlation between both signals using wavelet coherence and cross-correlation, evidenced the nature of their relationship (i.e., out of phase) and the existence of relatively constant time lag between both signals. Wavelet coherence proved to be likewise useful to identify specic periods of significant changes in the dynamics controlling streamflow generation. Furthermore, the analysis of EC and Q diurnal cycles allowed us to obtain new insights related to snow-dynamics and were also used to estimate the daily contribution to streamflow from snow-melting processes. The previous contributions may support future research on the different transfer functions that characterize water and solute transport in snow and ice-melting dominated catchments. Third, the need to understand how short and long-term climate variations may influence streamflow variability in Alpine environments lead us to the use of alternative techniques to analyse traditional long-term hydrological time series, i.e., precipitation (P), temperature (T) and streamflow (Q). We compared streamflow variability and explored the relationship between atmospheric forcing and streamflow of two case studies: Vermigliana and Sarca di Genova catchments, both located in the same region and presenting similar features, like the presence of glaciers in their upper part. Hovmöller diagrams and continuous wavelet transform were used to investigate daily and seasonal climate influences on streamflow variability, while wavelet coherence analysis was used to explore the periods on which two time series experienced oscillations at a similar frequency. Moreover, the use of these alternative techniques for data analysis and visualization, provided further insights into the hydrological response and sensitivity of the systems under study to climate changes, leading to the improvement of current conceptual models and allowing us to define a suitable framework for modelling applications, as foreseen within the following research element. The fourth element of this thesis, includes the application of an existing stochastic analytical modelling framework to the two case studies mentioned above, with the aim of characterizing and predicting streamflow distribution in these glacierized catchments. Results evidence that the size of glacier coverage on these type of catchments represents a very important feature of the system that needs to be taken account for, in fact, glaciers store a large amount of water as snow and ice, which can be rapidly released affecting signicantly the magnitude and distribution of streamflow.
Overall, the results obtained during this thesis provide new insights into the multi-faceted aspects of streamflow generation in snow and glacier dominated catchments, where geochemical data as an addition to hydrological information on real case studies played an essential role. Likewise, the application of different techniques for data analysis and visualization considering a variability of temporal scales provided valuable information about the sensitivity of Alpine systems to climate changes, which may serve as a support for water resources management in these important environments. Moreover, testing the applicability of an stochastic analytical approach to this complex context allowed us to understand the influence of the presence and size of glaciers on streamflow variability. Thus, the outcomes of this study may contribute to the improvement and development of new modelling structures
The cellular and molecular basis of the Nef requirement for HIV-1 infectivity
Get PDFNef is an HIV -1 accessory protein with a fundamental role for virus replication in vivo and for the development of AIDS. Among its several activities, Nef is essential for full HIV-1 infectivity, a function highly prominent in lymphoid cells. So far, the mechanism by which Nef promotes HIV-1 infectivity has remained elusive. Over the course of 3 years, my PhD research activity has led to the identification of the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as potent inhibitors of HIV-1 infectivity counteracted by the viral protein Nef [Rosa et al., 2015]. SERINC5 is predominantly localized on the plasma membrane where it is efficiently incorporated into budding HIV-1 virions and impairs subsequent virion penetration of susceptible target cells. Nef relocalizes SERINC5 to an endosomal compartment preventing its incorporation into HIV-1 particles. The ability to counteract SERINC5 is conserved in Nef proteins encoded by different primate immunodeficiency viruses, as well as in the structurally unrelated glycosylated Gag from murine leukaemia virus (MLV). These examples of functional conservation and convergent evolution emphasize the fundamental importance of SERINC5 in the interaction of the host with retroviral pathogens. Remarkably, SERINC5 potently inhibits HIV-1 even in the presence of Nef in a dose-dependent manner, suggesting that this cellular factor might be exploited as an anti-HIV-1 therapeutic gene
Modulation of Murine Intestinal Gene Expression by Dietary Fat: Spatial Variation and Saturation Effect
Get PDFThesis summary:
Traditional approaches investigate the linear effect of high-fat over-consumption on transcriptomic data. However, many biological processes occur in a nonlinear fashion.
The objective of this PhD thesis is to study the response types of dietary fat mediated differentially expressed genes (i.e., linear response; nonlinear response: logarithmic, exponential, quadratic and cubic) along the longitudinal axis of the small intestine. The main goal is to assess the presence of: (1) gene-specific response type, which refers to genes that preserve the same response pattern in the whole small intestine; (2) section-specific response type, which explains how particular genes behave in different ways according to the intestinal section where they are expressed. This thesis presents two genome-wide transcriptome analyses that quantified the effects of two dietary lipid interventions in different sections of the small intestine of C57BL/6J mice.
The first study includes the analysis of transcriptomic data collected from three sections of the small intestine (i.e., proximal, middle and distal). Data were collected after four weeks of dietary intervention during which mice were fed with various levels of fat (i.e., fat providing 10%, 20%, 30% or 45% kcal out of the total energy intake). Different intestinal sections were expected to exhibit regionalized functionality and display unique digestive and absorptive capacity. The goal was investigating linear and nonlinear (i.e., logarithmic, exponential, quadratic or cubic) transcriptomic responses as a continuous function of dietary fat intake along the longitudinal axis of small intestine. Middle section was the most responsive to dietary fat, and the majority of the genes showed linear response to fat intake. The highest relative importance of logarithmic (saturated) and exponential (unsaturated) response was in the proximal and in the distal section, respectively. Such pattern is coherent with the progressive absorption that occurs along the longitudinal axis of small intestine, with the hypothesis that when the absorptive capacity of the intestinal epithelia is overloaded the remaining fat will overflow to more distal sections. Processes related to inflammation responded in a gene-specific, linear way in the whole small intestine (mostly with up-regulated genes). Cholesterol transport and efflux exhibited section-specific response (i.e., genes were down-regulated with linear and exponential response in the proximal and middle intestine, respectively).
The second analysis was performed on transcriptomic data collected from ten sections of the small intestine. The intervention lasted two weeks and mice were fed with three types of diets (i.e., high-fat, low-fat or chow). Three types of transcriptomic responses (i.e., linear, logarithmic or quadratic) to dietary fat were tested. Dietary fat triggered the over-expression of processes related to metabolism and transport of lipids while the processes related to carbohydrate metabolism were down-regulated. Transport and metabolic processes of lipids were significantly associated to logarithmic and linear response, respectively. Middle and distal sections were the most sensitive to fat whereas the proximal section was not responsive to diet (this is due to the prevalence of digestive functions in the proximal small intestine).
Considering the complex physiology of small intestine and the influence of environmental effects such as diet and microbiota, nonlinear modelling of transcriptomic response to fat intake can provide a promising new avenue for research in molecular nutrition. The approach of studying nonlinear gene expression as a continuous function of fat intake allows the dynamic characterization of small intestine functioning. It can be used to illustrate the metabolic capacity of the small intestine or the presence of tipping points beyond which the relationship between fat intake and gene expression either weakens (logarithmic response) or strengthens (exponential response). Illustrating characteristic patterns of the gene- and section-specific response to dietary fat along the longitudinal axis of small intestine can contribute to better understand the relationships linking lipid intake to the development of obesity
Molecular Effects of the Nampt Inhibitor FK866 on Leukemia Cells
Get PDFAberrant activation of metabolic pathways has emerged as an hallmark of proliferating cancer cells and pharmaceutical approaches targeting cell metabolism hold great potential for cancer treatment. A critical factor in cellular
metabolism is nicotinamide adenine dinucleotide (NAD+) and cancer cells highly rely on it to face increased metabolic demands and proliferation rates. Intracellular NAD+ is a key metabolite involved in several cellular processes,
acting either as a coenzyme in redox reactions or as a substrate for NAD+-degrading enzymes such as poly (ADP-ribose) polymerases (PARPs), CD38, and sirtuins, regulating processes that undergo fundamental changes during
malignant transformation. Although NAD+ can be generated de novo from tryptophan precursor, the major route of biosynthesis is through a nicotinamidesalvage
process. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide in mammalian cells. A number of cancers
present an increased expression of NAMPT, and high NAMPT levels have been shown to be essential to support cancer cell growth, survival and EMT transition and to correlate with adverse prognosis. NAMPT is therefore a key factor regulating tumor cell metabolism and is thus considered a promising anti-cancer target. FK866 is a specific NAMPT inhibitor that lowers NAD+ concentration in cancer cells, reducing the activity of NAD+-dependent enzymes, impacting on ATP production and promoting cell death.
NAMPT inhibition was proven to be highly effective in both lymphoid and myeloid-derived hematological malignancies in preclinical studies without affecting healthy cells, such as hematopoietic stem cells. FK866 has completed
a phase I trial in oncology with advanced solid tumors. Thrombocytopenia was the dose-limiting toxicity, suggesting that this drug is a good candidate for clinical applications. We investigated the mechanism of action of FK866 in T-ALL derived cell lines as well as in primary leukemia cells. FK866-induced metabolic stress and
NAMPT ablation elicited a strong arrest of protein synthesis as early cell response. FK866 induced activation of the AMP-activated protein kinase (AMPK), which subsequently drove the inhibition of the mTOR/4EBP1 signaling cascade and of the major initiation factor EIF2A, impairing protein synthesis. Furthermore, FK866-induced stress reduced the levels of the anti-apoptotic protein MCL1 and impacted on the endoplasmic reticulum homeostasis. In addition, we established and characterized an FK866-resistant model derived from the T-ALL cell line Jurkat. Target-specific acquired resistance has been described after several therapies and can be modeled in vitro by growing cells
in presence of increasing concentrations of drug. In our resistant cells, FK866 treatment only partially impacted on NAD+ content, whereas ATP levels were recovered and protein translation resumed. Notably, during in vitro
acquisition of drug resistance, mutations in the NAMPT gene have not occurred. In the last years, many NAMPT inhibitors have been synthesized and characterized. The obtained results provide new insight into the role of the
NAMPT-mediated NAD+ salvage pathway in cancer cell metabolism and the molecular mechanisms of FK866, which will be useful to formulate specific and effective combinatorial drug therapies