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Econometric modelling for estimating direct flood damage to firms: a micro-scale approach using post-event records in Italy
No full textManaging flood risk is crucial for achieving global sustainability. Flood damage to firms' assets, in particular, imposes significant financial stress, necessitating efforts to minimize future consequences. However, current tools and knowledge for estimating flood damage to firms are inadequate, primarily due to a lack of high-quality damage data and the diversity of firm characteristics, complicating generalization. This study aims to improve understanding of micro-scale flood damage to firms in Italy through the analysis of empirical data, focusing specifically on direct damage. The dataset comprises 812 observed damage records collected after five flood events. Damage is categorized into building structure, stock, and equipment. The analysis reveals relationships between damage, economic sector, and water depth. Results indicate that damage increases at a rate less than proportional to the firm surface area and with water depth significantly explaining only stock damage. The quantification of damages across different sectors shows that healthcare facilities register the highest average damage to building structures, the commercial sector is most affected in terms of stock damage, and the manufacturing sector exhibits the greatest average damage to equipment. The derived damage model offers better predictive accuracy than foreign models in the Italian context. These findings aid in developing effective, tailored risk mitigation strategies and provide valuable insights for future research and policy aimed at reducing flood impacts on firms in Italy
DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF INDOLE-BASED COMPOUNDS AGAINST LEISHMANIASIS
No full textLeishmaniasis is a neglected tropical disease produced by Leishmania protozoan parasites, transmitted by the bite of infected female sandflies. The disease infects more than 12 million people worldwide and threatens additional hundreds of millions of people, primarily in the tropics and subtropics. Leishmaniasis manifests in a variety of clinical forms, ranging from self-healing cutaneous leishmaniasis to the fatal visceral form if untreated. Despite decades of use, current chemotherapy is limited to a few drugs such as pentavalent antimonials, amphotericin B, miltefosine, and paromomycin. However, these drugs typically have serious drawbacks such as relevant side effects, high costs, long treatment duration, and, most importantly, an increasing prevalence of drug-resistant strains. Thus, the search for new, effective, and safe therapeutic agents is an urgent need.
Among the many chemical scaffolds that have been screened for antiparasitic activity, indole derivatives are worth noting for their rich spectrum of biological activities and ability to bind to many biological targets. Over the last decade, several studies have reported the promising activity of indole-based molecules against different Leishmania species. Natural indole alkaloids, as well as synthetic derivatives such as bisindoles, indole-imidazoles, and others, have demonstrated potent antileishmanial effects both in vitro and in vivo. Therefore, the design and synthesis of new indole-derived compounds is a rational and attractive option in the search for new antileishmanial drugs.
In this context, the present thesis aims at identifying new antileishmanial compounds by designing, synthesising, and biologically investigating three groups of indole-based analogues: indole-imidazole hybrids, bisindoles, and indole isoindolinones.
Different indole-imidazoles have been synthesised following a previously reported procedure in the literature. However, this route presents limitations in the variability of imidazole substituents. In order to improve this limitation, two other synthetic routes were investigated. The first one, based on the Van Leusen reaction, resulted in a single analogue due to insurmountable limitations of the methodology. A new optimised procedure involving the alkylation of preformed imidazoles with 3-(2-iodoethyl)-1H-indole allowed the synthesis of new derivatives, increasing the covered chemical space.
Four different families of bisindoles have been synthesised to evaluate their biological activity against leishmaniasis. These families are: amines, amides, esters, and carboxylic acids. The introduction of glycosylated substituents has been performed in order to improve pharmacokinetics and activity.
The chemistry of indole-isoindolinone derivatives has been studied, allowing synthesising three different families of compounds: di-substituted, imines and di-substituted alkoxy derivatives.Leishmaniasis is a neglected tropical disease produced by Leishmania protozoan parasites, transmitted by the bite of infected female sandflies. The disease infects more than 12 million people worldwide and threatens additional hundreds of millions of people, primarily in the tropics and subtropics. Leishmaniasis manifests in a variety of clinical forms, ranging from self-healing cutaneous leishmaniasis to the fatal visceral form if untreated. Despite decades of use, current chemotherapy is limited to a few drugs such as pentavalent antimonials, amphotericin B, miltefosine, and paromomycin. However, these drugs typically have serious drawbacks such as relevant side effects, high costs, long treatment duration, and, most importantly, an increasing prevalence of drug-resistant strains. Thus, the search for new, effective, and safe therapeutic agents is an urgent need.
Among the many chemical scaffolds that have been screened for antiparasitic activity, indole derivatives are worth noting for their rich spectrum of biological activities and ability to bind to many biological targets. Over the last decade, several studies have reported the promising activity of indole-based molecules against different Leishmania species. Natural indole alkaloids, as well as synthetic derivatives such as bisindoles, indole-imidazoles, and others, have demonstrated potent antileishmanial effects both in vitro and in vivo. Therefore, the design and synthesis of new indole-derived compounds is a rational and attractive option in the search for new antileishmanial drugs.
In this context, the present thesis aims at identifying new antileishmanial compounds by designing, synthesising, and biologically investigating three groups of indole-based analogues: indole-imidazole hybrids, bisindoles, and indole isoindolinones.
Different indole-imidazoles have been synthesised following a previously reported procedure in the literature. However, this route presents limitations in the variability of imidazole substituents. In order to improve this limitation, two other synthetic routes were investigated. The first one, based on the Van Leusen reaction, resulted in a single analogue due to insurmountable limitations of the methodology. A new optimised procedure involving the alkylation of preformed imidazoles with 3-(2-iodoethyl)-1H-indole allowed the synthesis of new derivatives, increasing the covered chemical space.
Four different families of bisindoles have been synthesised to evaluate their biological activity against leishmaniasis. These families are: amines, amides, esters, and carboxylic acids. The introduction of glycosylated substituents has been performed in order to improve pharmacokinetics and activity.
The chemistry of indole-isoindolinone derivatives has been studied, allowing synthesising three different families of compounds: di-substituted, imines and di-substituted alkoxy derivatives
Michelangelo tra parola e immagine: un percorso negli autografi e negli studi di architettura
No full textIl contributo si concentra sul tema del rapporto tra parola e immagine all'interno del corpus autografo michelangiolesco, valutando le modalità di interrelazione tra componente testuale e iconografica a seconda della tipologia di scritto. Segue un'analisi specifica dei progetti e degli scritti di architettura redatti dall'artista durante la gestione dei cantieri di San Lorenzo a Firenze, nel periodo 1516-1534
EFFECT OF EXERCISE ON THE INSULIN/IGF-1 SYSTEM IN CANCER PATIENTS - IMPLICATIONS FOR CARDIOMETABOLIC HEALTH AND QUALITY OF LIFE IN BREAST CANCER SURVIVORS AND OLDER ADULTS
No full textBreast Cancer (BC) is the most common female cancer worldwide, and the growing number of adults aged ≥ 65 is expected to increase the population of elderly Breast Cancer Survivors (BCS). However, the effect of tailored aerobic exercise and Mediterranean diet (MD) on overall Quality of Life (QoL) considering fatigue, cardiometabolic health, glucose homeostasis, and the tumor growth regulation, remain unclear. Moreover, the role of reserve of oxygen uptake (V̇O2R) and fatigability as determinant of free-living energy expenditure in older adults is still unknown. Since cancer history is associated with higher fatigability and poor physical functioning, especially in older adults, this Thesis aimed to: (i) investigated the effect of a Lifestyle Intervention (LI), combining supervised aerobic exercise and MD guidance, on a) QoL including cancer-related fatigue (study 1); b) free-living glycemic profile (study 2); and c) Insulin-Like Growth Factor 1 (IGF-1) modulation (study 3) along with cardiometabolic health (e.g., maximum oxygen uptake [V̇O2max], % of fat mass, and caloric intake) in BCS within the MoviS clinical trial; and (ii) to examine V̇O2R and perceived fatigability as determinants of Activity Energy Expenditure (AEE) in older adults from the ENGAGE project (study 4). Four different studies were conducted: studies 1-3 recruited and randomized BCS into Control (GC) and Intervention (IG) groups, while study 4 followed a cross-sectional design. Study 1 showed that LI improved QoL and cardiometabolic health (e.g., physical functioning and V̇O2max) in the short-term. However, benefits returned to the baseline in the long-term, emphasize the need for follow-up education to sustain healthy habits. MD guidance was insufficient to achieve optimal adherence, and age and Tamoxifen influencing QoL changes. Study 2 suggested that the LI improved free-living glycemic control (e.g., insulin level) more in the IG than in the CG. CG showed a worsening trend in time spent above glucose range (> 180 mg/dl). These effects were related to food intake between active and non-active days. Study 3 showed the baseline IGF-1 role in assessing LI efficacy: V̇O2max improvements were associated with an increase in IGF-1 in participants with low baseline levels and with a decrease in those with high levels. Study 4 found V̇O2R significantly correlated with fatigability and AEE, and V̇O2R, age and % of fat mass were predictors of AEE. Four functional profiles were detected confirming that fatigability was significantly different for women compared to men. Although fatigability was not a predictor of AEE, it was significantly associated to V̇O2R. This Thesis showed the complex interplay between self-reported outcomes (e.g., QoL and fatigability) and physiological component (e.g., V̇O2max, and IGF-1) in two different cohorts. Integrating these measures is essential to understand QoL and cardiometabolic health in order to prevent BC incidence favoring healthy ageing.Breast Cancer (BC) is the most common female cancer worldwide, and the growing number of adults aged ≥ 65 is expected to increase the population of elderly Breast Cancer Survivors (BCS). However, the effect of tailored aerobic exercise and Mediterranean diet (MD) on overall Quality of Life (QoL) considering fatigue, cardiometabolic health, glucose homeostasis, and the tumor growth regulation, remain unclear. Moreover, the role of reserve of oxygen uptake (V̇O2R) and fatigability as determinant of free-living energy expenditure in older adults is still unknown. Since cancer history is associated with higher fatigability and poor physical functioning, especially in older adults, this Thesis aimed to: (i) investigated the effect of a Lifestyle Intervention (LI), combining supervised aerobic exercise and MD guidance, on a) QoL including cancer-related fatigue (study 1); b) free-living glycemic profile (study 2); and c) Insulin-Like Growth Factor 1 (IGF-1) modulation (study 3) along with cardiometabolic health (e.g., maximum oxygen uptake [V̇O2max], % of fat mass, and caloric intake) in BCS within the MoviS clinical trial; and (ii) to examine V̇O2R and perceived fatigability as determinants of Activity Energy Expenditure (AEE) in older adults from the ENGAGE project (study 4). Four different studies were conducted: studies 1-3 recruited and randomized BCS into Control (GC) and Intervention (IG) groups, while study 4 followed a cross-sectional design. Study 1 showed that LI improved QoL and cardiometabolic health (e.g., physical functioning and V̇O2max) in the short-term. However, benefits returned to the baseline in the long-term, emphasize the need for follow-up education to sustain healthy habits. MD guidance was insufficient to achieve optimal adherence, and age and Tamoxifen influencing QoL changes. Study 2 suggested that the LI improved free-living glycemic control (e.g., insulin level) more in the IG than in the CG. CG showed a worsening trend in time spent above glucose range (> 180 mg/dl). These effects were related to food intake between active and non-active days. Study 3 showed the baseline IGF-1 role in assessing LI efficacy: V̇O2max improvements were associated with an increase in IGF-1 in participants with low baseline levels and with a decrease in those with high levels. Study 4 found V̇O2R significantly correlated with fatigability and AEE, and V̇O2R, age and % of fat mass were predictors of AEE. Four functional profiles were detected confirming that fatigability was significantly different for women compared to men. Although fatigability was not a predictor of AEE, it was significantly associated to V̇O2R. This Thesis showed the complex interplay between self-reported outcomes (e.g., QoL and fatigability) and physiological component (e.g., V̇O2max, and IGF-1) in two different cohorts. Integrating these measures is essential to understand QoL and cardiometabolic health in order to prevent BC incidence favoring healthy ageing
Relational Information Towards a New Kind of Information in Quantum Mechanics
No full textThis paper argues that von Neumann entropy plays two conceptually distinct roles in quantum theory. When applied to global mixed states, it expresses the quantum analogue of the informational entropy. But when applied to reduced states of entangled systems, it measures objective physical correlations. We propose that this second usage realizes a new informational kind, which we call relational information. Unlike information in communication theory, it reflects structural interdependence between systems, not probability about a certain outcome. We further suggest that this informational kind has ontological significance: relational information is a physically instantiated feature of entangled systems, and not merely an agent-relative concept
Latest Developments in Direct and Non-Direct LC-MS Methods Based on Liquid Electron Ionization (LEI)
Full text linkMass spectrometry (MS) enables precise identification and quantification of molecules, particularly when combined with chromatography. The advent of atmospheric pressure ionization (API) techniques allowed the efficient coupling of liquid chromatography with MS (LC-MS), extending analyses to nonvolatile and thermolabile compounds. API techniques present limitations such as low informative capacity and reproducibility of mass spectra, increasing instrument complexity and costs. Other challenges include analyzing poorly polar molecules and matrix effects (ME), which negatively impact quantitative analyses, necessitating extensive sample purification or using expensive labeled standards. These limitations prompted the exploration of alternative solutions, leading to the development of the Liquid Electron Ionization (LEI) interface. The system has demonstrated excellent robustness and reproducibility. LEI has been employed to analyze various compounds, including pesticides, drugs of abuse, phenols, polycyclic aromatic hydrocarbons (PAHs), phthalates, and many others. Its versatility has been validated with single quadrupole, triple quadrupole, and QToF detectors, operating in electron ionization (EI) or chemical ionization (CI) modes
and with both reverse phase liquid chromatography (RPLC) and normal phase liquid chromatography (NPLC). LEI has also been successfully integrated with the Microfluidic Open Interface (MOI), Membrane Introduction Mass Spectrometry (MIMS), and Microfluidic Water-Assisted Trap Focusing (M-WATF), broadening its application scope and consistently demonstrating promising results in terms of sensitivity and identification power. The most recent advancement is the development of Extractive-Liquid Sampling Electron Ionization-Mass Spectrometry (E-LEI-MS), a surface sampling and real-time analysis technique based on the LEI concept. This review article offers a comprehensive and up-to-date picture of the potential of LEI
