49112 research outputs found
Sort by
Relational Quantum Mechanics and (Soft) Perspectivism
No full textThis paper examines the role of perspectivism in Relational Quantum Mechanics,
situating it within the broader landscape of quantum interpretations and the scientific
realism debate. We argue that, while interpretations such as QBism embrace
strong forms of perspectivism, Relational Quantum Mechanics adopts a “soft” perspectivism,
limiting the observer’s role to selecting experimental contexts without
compromising its realist framework. We also explore the historical roots of Relational
Quantum Mechanics, showing that relational ideas in the works of Bohr and
other pioneers similarly avoided strong perspectivist commitments. By analyzing
both contemporary and historical perspectives, we argue that Relational Quantum
Mechanics offers a minimalist yet robust relational interpretation, distinct from
more subjectivist approache
Design of Experiments-Based Development of UHPLC Methods for Targeted Analysis of Phytoplankton Pigments and Phycocyanin in Aquatic Samples: Characterization for Chemotaxonomic and Remote Sensing Applications
No full textThe accurate quantification of phytoplankton pigments is critical for understanding aquatic ecosystem dynamics, supporting satellite algorithm validation, and advancing chemotaxonomic and biodiversity studies. This doctoral thesis shows the development, optimization, and validation of two independent Ultra-High Performance Liquid Chromatography (UHPLC) methods for pigment analysis in marine and inland water samples, both guided by a Design of Experiments (DoE) strategy. The first method addresses the need for a more efficient and environmentally sustainable analysis of phytoplankton pigment diversity. A novel ethanol-based UHPLC method using a core-shell C8 chromatographic column was developed to resolve 33 ecologically relevant pigments, including challenging pairs such as divinyl/monovinyl chlorophylls and xanthophyll isomers. The optimization, based on a central composite DoE design, enabled full resolution in under 26 minutes, reducing both toxic solvent use and analysis time. The method was validated on standards, algal cultures, and natural samples from the northwestern Adriatic Sea. The second UHPLC method targets the quantification of phycocyanin (C-PC), a key pigment in cyanobacteria, extracted from concentrated filter-based samples—commonly collected in satellite validation campaigns. A fullfactorial DoE was applied to compare extraction conditions, optimize chromatographic separation on a reversed-phase C5 chromatographic column using an acetonitrile gradient, and validate the method on natural samples and algal cultures for sensitivity, accuracy, and reproducibility. The result is a fast and robust UHPLC protocol suitable for routine monitoring of cyanobacterial blooms and satellite product validation. Together, these analytical advancements contribute to the development of more reliable tools for aquatic pigment quantification, offering critical support for satellite remote sensing calibration, phytoplankton functional type discrimination, and environmental monitoring programs.The accurate quantification of phytoplankton pigments is critical for understanding aquatic ecosystem dynamics, supporting satellite algorithm validation, and advancing chemotaxonomic and biodiversity studies. This doctoral thesis shows the development, optimization, and validation of two independent Ultra-High Performance Liquid Chromatography (UHPLC) methods for pigment analysis in marine and inland water samples, both guided by a Design of Experiments (DoE) strategy. The first method addresses the need for a more efficient and environmentally sustainable analysis of phytoplankton pigment diversity. A novel ethanol-based UHPLC method using a core-shell C8 chromatographic column was developed to resolve 33 ecologically relevant pigments, including challenging pairs such as divinyl/monovinyl chlorophylls and xanthophyll isomers. The optimization, based on a central composite DoE design, enabled full resolution in under 26 minutes, reducing both toxic solvent use and analysis time. The method was validated on standards, algal cultures, and natural samples from the northwestern Adriatic Sea. The second UHPLC method targets the quantification of phycocyanin (C-PC), a key pigment in cyanobacteria, extracted from concentrated filter-based samples—commonly collected in satellite validation campaigns. A fullfactorial DoE was applied to compare extraction conditions, optimize chromatographic separation on a reversed-phase C5 chromatographic column using an acetonitrile gradient, and validate the method on natural samples and algal cultures for sensitivity, accuracy, and reproducibility. The result is a fast and robust UHPLC protocol suitable for routine monitoring of cyanobacterial blooms and satellite product validation. Together, these analytical advancements contribute to the development of more reliable tools for aquatic pigment quantification, offering critical support for satellite remote sensing calibration, phytoplankton functional type discrimination, and environmental monitoring programs
Non-Targeted Analysis of Carbofuran and Related Compounds in Commercial Formulations and Animal Tissue
No full textRecently, some cases of intentional animal poisoning using Carbofuran (CF) occurred in the Czech Republic, although CF is no longer available in the EU market. The present study describes a novel non-targeted analysis (NTA) workflow developed to possibly characterize 13 CF formulations from various sources to be certainly identified in real samples. Furthermore, a detection and quantification method for CF was developed for analyzing three animal samples, obtained from dead animals. The analyses were con-ducted using the liquid electron ionization (LEI) interface coupled with a quadrupole time-of-flight (QTOF) mass spectrometer, allowing the simultaneous characterization of the formulation's volatile and low-volatile fractions. Almost all compounds detected in the different formulations were identified by comparing the experimental spectra with the NIST library at high probability values (95–99.38%). Determination of molecular ions, fol-lowed by MS/MS analysis, was performed to confirm compound identities at a high level of confidence. The quantification method for CF was successfully validated, showing neg-ligible matrix effects (107%). CF was detected in two out of the three real samples. Only 3-keto-carbofuran was detected in one of the real samples; without any other marker, it was not possible to identify the specific formulation used in the three poisoning cases
Educare al pensiero critico. Orientamenti curricolari per una scuola dello sviluppo umano
No full textThe study takes as its object of investigation the education of critical thinking, beginning with an analysis of certain features of twenty-first-century society and of the educational implications that may be derived from them.
The postmodern era is characterized by the paradigm of complexity (Morin, 2017). In this sense, contemporary society is composed of a plurality of interacting levels that structure a reality which cannot be interpreted through univocal or homogeneous readings, but rather requires a sophisticated plurality of interwoven perspectives. Critical thinking education, therefore, emerges as one of the key means of addressing an era such as the present—an era marked by profound social, ideological, and cultural fragmentation, and traversed by deep and ongoing transformations, from climate change to the digital revolution, which are reflected in significant anthropological changes.
It is argued that the contemporary condition calls for the valorization of the ideals invoked by the paradigm of human development in a democratic direction (Sen, 2001; Nussbaum, 2011), as principles that should inspire and guide educational and instructional processes. From a pedagogical standpoint, two dimensions emerge, which Bertin (1968/2021) already identified as constitutive of education—and of an education of reason—namely, the intellectual and the ethical-social. At their intersection lies the perspective of critical thinking as an essential educational need for citizens of the twenty-first century.
In this regard, the study reflects on the conditions of possibility for critical thinking education within the school context. To this end, a theoretical investigation was conducted into the nature of critical thinking, alongside an exploratory inquiry aimed at examining the opinions and practices of upper secondary school teachers concerning the education of this form of thinking.
In light of the findings, the study considers the opportunity to frame such education as a key curricular dimension, conceiving critical thinking as a transversal form of education to be implemented within the perspective of the integrated curriculum. In particular, it is argued that the development of critical thinking constitutes a process of deutero-learning and, as such, pertains to a curriculum of second-order logic. Consequently, it was deemed appropriate to formulate a curriculum hypothesis grounded in a model of curricular design based on principles of contextual and procedural structuring, which appears most suited to the logical typology of curriculum under consideration. Within this framework, a theoretical proposal of curricular orientations for critical thinking education in upper secondary school was elaborated. The proposed principles of contextual and procedural structuring were subsequently submitted for evaluation to an international panel of academic experts.The study takes as its object of investigation the education of critical thinking, beginning with an analysis of certain features of twenty-first-century society and of the educational implications that may be derived from them.
The postmodern era is characterized by the paradigm of complexity (Morin, 2017). In this sense, contemporary society is composed of a plurality of interacting levels that structure a reality which cannot be interpreted through univocal or homogeneous readings, but rather requires a sophisticated plurality of interwoven perspectives. Critical thinking education, therefore, emerges as one of the key means of addressing an era such as the present—an era marked by profound social, ideological, and cultural fragmentation, and traversed by deep and ongoing transformations, from climate change to the digital revolution, which are reflected in significant anthropological changes.
It is argued that the contemporary condition calls for the valorization of the ideals invoked by the paradigm of human development in a democratic direction (Sen, 2001; Nussbaum, 2011), as principles that should inspire and guide educational and instructional processes. From a pedagogical standpoint, two dimensions emerge, which Bertin (1968/2021) already identified as constitutive of education—and of an education of reason—namely, the intellectual and the ethical-social. At their intersection lies the perspective of critical thinking as an essential educational need for citizens of the twenty-first century.
In this regard, the study reflects on the conditions of possibility for critical thinking education within the school context. To this end, a theoretical investigation was conducted into the nature of critical thinking, alongside an exploratory inquiry aimed at examining the opinions and practices of upper secondary school teachers concerning the education of this form of thinking.
In light of the findings, the study considers the opportunity to frame such education as a key curricular dimension, conceiving critical thinking as a transversal form of education to be implemented within the perspective of the integrated curriculum. In particular, it is argued that the development of critical thinking constitutes a process of deutero-learning and, as such, pertains to a curriculum of second-order logic. Consequently, it was deemed appropriate to formulate a curriculum hypothesis grounded in a model of curricular design based on principles of contextual and procedural structuring, which appears most suited to the logical typology of curriculum under consideration. Within this framework, a theoretical proposal of curricular orientations for critical thinking education in upper secondary school was elaborated. The proposed principles of contextual and procedural structuring were subsequently submitted for evaluation to an international panel of academic experts
Introduzione alla nuova edizione di I. Mancini, Kant e la teologia
No full textLo scritto introduce la nuova edizione del volume di I. Mancini, Kant e la teologia (1975), tracciando un bilancio della interpretazione kantiana di Mancini successiva al libro e i motivi portanti e attuali di quest'ultimo
Rapid and high-throughput analysis of PAHs and pesticides adsorbed on microplastics using SPME-MS through a microfluidic open interface coupled to liquid electron ionization mass spectrometry
No full textMicroplastics (MPs) are pervasive contaminants in aquatic environments, capable of adsorbing and transporting hazardous chemicals such as polycyclic aromatic hydrocarbons (PAHs) and pesticides. Understanding these adsorption processes is crucial for evaluating their ecological and health risks. In this study, a green analytical approach with a high-throughput, solid-phase microextraction coupled with a microfluidic open interface and liquid electron ionization mass spectrometry (SPME-MOI-LEI-MS), was applied to investigate the kinetics and thermodynamics of PAHs and pesticides adsorption on low-density polyethylene (LDPE) and polypropylene (PP) microplastics. Method optimization and validation demonstrated intraday RSD values below 15% and limits of quantification below 10 μg/L. Results revealed that PAHs adsorb predominantly through non-polar interactions, with adsorption efficiency correlating with analyte hydrophobicity. For pesticides, adsorption patterns were more diverse, reflecting differences in molecular structure and physicochemical properties. Notably, chlorpyrifos
exhibited high affinity for LDPE (95% recovery), raising concern due to its toxicity. Competition experiments
further highlighted how strongly adsorbing molecules can inhibit the uptake of weaker ones as adsorption capacity
at the equilibrium of atrazine, metalaxyl, dichlorvos and alachlor increases in absence of chlorpyrifos
Unraveling G Protein-Coupled Receptor Allosteric Modulation through Computational Approaches
No full textThe development of new drugs is a multidisciplinary process that is time-consuming and expensive. Computer-Aided Drug Design (CADD) is essential for accelerating the drug discovery process. GPCRs represent a large and pharmacologically important family of proteins involved in essential cellular signaling pathways. As of mid-2025, approximately 36% of all FDA-approved drugs target GPCRs, 99% of which bind to the primary endogenous ligand site, known as the orthosteric site. However, the growing availability of experimental GPCR structures has revealed a rich diversity of allosteric binding sites—regions distinct from the orthosteric site that modulate receptor function in subtle and often highly selective ways. Allosteric modulation offers promising opportunities to enhance drug efficacy, selectivity, and chemical diversity; however, a systematic understanding of its mechanisms is still developing.
This work is structured around three main chapters. The first part introduces an annotation scheme for GPCRs that structurally classifies binding sites based on receptor class, contacts with transmembrane helices, and topology relative to the membrane. Applied to 100 GPCR-ligand complexes, this framework identifies 24 distinct allosteric sites and evaluates site-detection algorithms (BioGPS, SiteMap, and FTMap), with BioGPS performing best. Property analysis shows that extrahelical allosteric pockets tend to be shallow and low in volume, and that their ligands are enriched in halogens, indicating a distinct chemical space. Combining receptor and ligand similarity enables effective prediction of ligandability, despite challenges posed by ligand-induced conformational changes at the binding sites.
In the second part, the Atlas algorithm, originally developed for globular proteins, was refined by integrating known extra-helical ligand fragments for GPCRs and recalibrating cavity contributions to account for shallow allosteric pockets at the protein-membrane interface. This optimized version successfully identified 96% of validated allosteric sites in GPCRs and was retrospectively validated through structure-activity relationship (SAR) analysis. Prospective validation included the synthesis and binding confirmation of hybrid probe ligands targeting hot spots in the complement C5a receptor (C5AR1) and the cannabinoid receptor 1 CNR1), highlighting Atlas’s utility in allosteric drug design without requiring prior knowledge.
The third and final study explores how allosteric modulators influence protein dynamics. A total of 45 μs of molecular dynamics simulations were analyzed across four Class A GPCRs C5AR1, P2YR1), CNR1/CNR2 to capture dynamic features of shallow extra-helical sites. Focusing on Allosteric Communication Networks (ACNs), the shortest paths were calculated between orthosteric site and G-protein interface. This analysis revealed communication patterns specific to conformational state and ligand. The ACN analysis guided a mutagenesis study on CNR2, which revealed the crucial role of this residue G2105.59 in the differential pharmacological profile of Ec21a in CNR1 versus CNR2.
This thesis demonstrates how the combination of GPCR crystallographic structures, computational methods, and experimental techniques can yield new insights into allosterism, enabling the rational design of novel allosteric ligands in the future.The development of new drugs is a multidisciplinary process that is time-consuming and expensive. Computer-Aided Drug Design (CADD) is essential for accelerating the drug discovery process. GPCRs represent a large and pharmacologically important family of proteins involved in essential cellular signaling pathways. As of mid-2025, approximately 36% of all FDA-approved drugs target GPCRs, 99% of which bind to the primary endogenous ligand site, known as the orthosteric site. However, the growing availability of experimental GPCR structures has revealed a rich diversity of allosteric binding sites—regions distinct from the orthosteric site that modulate receptor function in subtle and often highly selective ways. Allosteric modulation offers promising opportunities to enhance drug efficacy, selectivity, and chemical diversity; however, a systematic understanding of its mechanisms is still developing.
This work is structured around three main chapters. The first part introduces an annotation scheme for GPCRs that structurally classifies binding sites based on receptor class, contacts with transmembrane helices, and topology relative to the membrane. Applied to 100 GPCR-ligand complexes, this framework identifies 24 distinct allosteric sites and evaluates site-detection algorithms (BioGPS, SiteMap, and FTMap), with BioGPS performing best. Property analysis shows that extrahelical allosteric pockets tend to be shallow and low in volume, and that their ligands are enriched in halogens, indicating a distinct chemical space. Combining receptor and ligand similarity enables effective prediction of ligandability, despite challenges posed by ligand-induced conformational changes at the binding sites.
In the second part, the Atlas algorithm, originally developed for globular proteins, was refined by integrating known extra-helical ligand fragments for GPCRs and recalibrating cavity contributions to account for shallow allosteric pockets at the protein-membrane interface. This optimized version successfully identified 96% of validated allosteric sites in GPCRs and was retrospectively validated through structure-activity relationship (SAR) analysis. Prospective validation included the synthesis and binding confirmation of hybrid probe ligands targeting hot spots in the complement C5a receptor (C5AR1) and the cannabinoid receptor 1 CNR1), highlighting Atlas’s utility in allosteric drug design without requiring prior knowledge.
The third and final study explores how allosteric modulators influence protein dynamics. A total of 45 μs of molecular dynamics simulations were analyzed across four Class A GPCRs C5AR1, P2YR1), CNR1/CNR2 to capture dynamic features of shallow extra-helical sites. Focusing on Allosteric Communication Networks (ACNs), the shortest paths were calculated between orthosteric site and G-protein interface. This analysis revealed communication patterns specific to conformational state and ligand. The ACN analysis guided a mutagenesis study on CNR2, which revealed the crucial role of this residue G2105.59 in the differential pharmacological profile of Ec21a in CNR1 versus CNR2.
This thesis demonstrates how the combination of GPCR crystallographic structures, computational methods, and experimental techniques can yield new insights into allosterism, enabling the rational design of novel allosteric ligands in the future
La grafica povera nel contesto urbano: il caso di Venezia
No full textA fronte di numerosi studi sulla stampa povera e i materiali a stampa effimeri in relazione all’ambiente urbano in epoca rinascimentale e moderna, sembra oggi necessario attualizzare il tema prendendo in considerazione materiali grafici poveri che vengono esposti o che sono in circolazione nella città contemporanea.
La transizione digitale e la portabilità degli schermi, assieme alla diffusione di tecnologie a basso costo per office e home printing hanno rivoluzionato la comunicazione urbana allargando il pubblico di produttori e aumentando vorticosamente la circolazione dei materiali di comunicazione grafico-visivi.
Dopo aver tentato una definizione di grafica povera capace di articolare la relazione tra i concetti di materiale povero e segno povero, il testo procederà alla stesura di un possibile modello di descrizione e analisi della grafica povera che sia capace non solo di una descrizione stilistica, ma anche di dare conto di fattori contestuali e relazionali che caratterizzano gli artefatti grafico-visivi nelle loro diversa fasi di esistenza, dalla concezione alla produzione, dalla circolazione al consumo.
Come evidenziato in Ephemeral City: Cheap Print and Urban Culture in Renaissance Venice da Rosa Salzbert, Venezia, per le sue caratteristiche geografiche, sociali ed economiche ha rappresentato in epoca rinascimentale, un caso emblematico per lo studio non solo della stampa ufficiale, ma anche della stampa povera ed effimera. Ancora oggi, le peculiarità della città la rendono un luogo di osservazione privilegiato in cui è possibile osservare la compresenza di prodotti molteplici legati a una diversità di attori e pubblici, tempi e modi della comunicazione
SEYO 2024. Musica, relazioni e organizzazione in un’esperienza educativa intensiva
No full textIl report presenta i risultati di una ricerca qualitativa condotta sull’esperienza di SEYO 2024 (Sistema Europe Youth Orchestra), svoltasi tra Pesaro e Urbino nel luglio 2024 nell’ambito di Pesaro Capitale Italiana della Cultura, in collaborazione con l’associazione LiberaMusica. L’indagine analizza SEYO come dispositivo temporaneo ad alta intensità relazionale, educativa e organizzativa, capace di rendere visibili in forma concentrata dinamiche tipiche delle pratiche di educazione musicale collettiva orientate all’inclusione sociale. La ricerca si fonda su un corpus eterogeneo di materiali empirici – diari riflessivi, questionari, osservazioni etnografiche, focus group e conversazioni informali – che consentono di ricostruire l’esperienza da prospettive multiple, intrecciando vissuti individuali, pratiche collettive e condizioni materiali e organizzative. I risultati sono organizzati attorno a nove dimensioni analitiche che mettono in luce il carattere intensivo e immersivo del campus, il ruolo del corpo e della fatica, il lavoro organizzativo spesso invisibile, le relazioni educative, le tensioni legate a inclusione e gerarchie implicite, le dinamiche di socialità e intercultura e gli esiti in termini di apprendimento e motivazione. Il report propone infine una lettura complessiva dell’esperienza, evidenziandone il carattere strutturalmente ambivalente: SEYO emerge al tempo stesso come potente acceleratore di relazioni e apprendimenti e come contesto che rende visibili fragilità, limiti e asimmetrie, offrendo spunti di riflessione per il lavoro educativo e culturale orientato all’inclusione