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Impact of leakage during HFC-125 production on the increase in HCFC-123 and HCFC-124 emissions
No full textIdentification of pyrazolo-piperidinone derivatives targeting YAP-TEAD interface 3 as anticancer agents through integrated virtual screening and mass spectrometry proteomics
No full textThe transcriptional activity of TEAD4 (transcriptional enhancer associated domain proteins), one of the final effectors of the Hippo pathway, can be dysregulated or mutated in cancer. Consequently, targeting the interaction between TEAD and its co-activator YAP (Yes Associated Protein) to disrupt the YAP:TEAD (Y:T) heterodimer has emerged as a promising anti-cancer strategy. Therefore, in this study, we aimed to identify novel scaffolds targeting the TEAD Interface 3 surface as effective anticancer agents against colorectal and ovarian cancer. Employing virtual screening, molecular dynamics, computational ADME-T prediction, and synthetic chemistry, we initially identified novel pyrazolo-piperidinone compounds exhibiting binding affinities (Kd) between 0.6 and 10 μM towards TEAD4 Interface 3 in a fluorescence anisotropy assay, with 6a as the initial lead for a library of 20 compounds. A few of them demonstrated effective and well-characterized cellular antiproliferative activity against HCT116 and A2780 cancer cells. They demonstrated efficacy against colorectal cancer cells resistant to the KRAS-dependent clinical candidate IAG933 and confirmed the ability to inhibit TEAD4 target genes expression. Mass spectrometry-based proteomics of HCT116 cells treated with verteporfin and 6a analogs revealed a proteome modulation consistent with an anti-TEAD mechanism of action, revealing the downregulation of CTGF and TGF-β1. Bioinformatic metabolic pathway analysis further differentiated the mechanism of action of the 6a analogs from verteporfin, a known indirect modulator of the Y:T complex. These findings establish the pyrazolo-piperidinone class as novel Y:T disruptors and provide insights into their metabolic impact on downstream effectors, offering a valuable framework for future hit-to-lead optimization and mechanism of action studies
Le corone dell’imperatore
No full textL'esame delle corone indossate da Adriano e note dai suoi ritratti ufficiali evidenzia l'uso mai attestato prima in contesto imperiale della corona di pino. Essa, insieme all'abbigliamento 'civile', deve essere interpretata non solo nell'ambito del philellenion promosso da Adriano, ma in quello specifico dei giochi che si svolgevano durante il festival, sì da suggerire il ruolo di agonoteta dell'imperatore
Brand hate and consumers’ responses: An analysis in the offline and online environment
No full textWithin the studies investigating the consumer-brand relationships, brand hate has been partially disregarded as a research topic. This paper aims to extend the analysis of the brand hate outcomes by considering both their offline and online nature (i.e., offline/online negative word-of-mouth (NWOM) and offline/online complaining) and by also testing the role of concern for others and venting negative feelings as possible mediators on the relationship between brand hate and both offline/online behavioural outcomes. To reach this objective, structural equation modelling has been employed on a sample of 493 consumers. Findings reveal that concern for others is mainly involved when consumers perform NWOM in the offline context among their friends/family, while venting negative feelings is the main motive in the online context and for complaining to the company. The paper provides managerial implications useful to manage the consumers’ offline/online behaviours in the brand hate context
Global Structure of Dependency and Socio-ecological Crisis: Intersecting Delinking and Degrowth for an Ecosocialist Transition
Get PDFNeoliberal globalization has led to a functional differentiation between an extractive periphery providing natural resources and a productive periphery
providing labor for capital accumulation in the center through unequal exchange. The global structure of dependency inherited from colonialism has not been substantially altered, thus challenging the development strategies of peripheral countries. The question of delinking from the global capitalist market for an autocentric economic model to escape dependency is back on the agenda. Democratic economic and ecological planning, combined with a paradigm shift from a quantitative conception of development to a
qualitative conception of well-being, are integral to this alternative strategy. In this framework, delinking of the global South and degrowth of the global North configure an eco-socialist transition out of the global socio-ecological
crisis
Transversal Skills and Professional Motivation in Qualifying Courses for Secondary School: An Exploratory Investigation.
No full textTeacher training represents a crucial challenge for the construction of equitable, inclusive and accessible school contexts. Training courses tend to focus on increasing knowledge instead of examining the factors that help people cope with uncertainty and stress. The paper intends to examine the profile of teachers participating in the qualifying courses for lower and upper secondary schools (30/36 and 60 credits), with particular attention to emotional and motivational aspects. The exploratory research, conducted through a qualitative-quantitative approach, highlights that students acknowledge the importance of transversal skills in professional action, feeling vulnerable to situations of anxiety, fear and shame. These results stress the importance of developing training courses that promote adequate reflection on all dimensions, including relational, cognitive and social aspects
Privacy-preserving LLM-based chatbots for hypertensive patient self-management
Get PDFMedical chatbots are becoming a basic component in telemedicine, propelled by advancements in Large Language Models (LLMs). However, LLMs’ integration into clinical settings comes with several issues, with privacy concerns being particularly significant. The paper proposes a tailored architectural solution and an information workflow that address privacy issues, while preserving the benefits of LLMs. We examine two solutions to prevent the disclosure of sensitive information: (i) a filtering mechanism that processes sensitive data locally but leverage a robust OpenAI’s online LLM for engaging with the user effectively, and (ii) a fully local deployment of open-source LLMs. The effectiveness of these solutions is assessed in the context of hypertension management across various tasks, ranging from intent recognition to reliable and emphatic conversation. Interestingly, while the first solution proved to be more robust in intent recognition, an evaluation by domain experts of the models’ responses, based on reliability and empathetic principles, revealed that two out of six open LLMs received the highest scores. The study underscores the viability of incorporating LLMs into medical chatbots. In particular, our findings suggest that open LLMs can offer a privacy-preserving, yet promising, alternative to external LLM services, ensuring safer and more reliable telemedicine practices. Future efforts will focus on fine-tuning local models to enhance their performance across all tasks
Filologia, storia, geografia. Questioni e prospettive. Urbino, 25-26 Ottobre 2023
No full textIl volume accoglie gli atti del convegno «Filologia, Storia e Geografia: questioni e prospettive» (25 e 26 ottobre 2023) tenutosi all’Università degli Studi di Urbino Carlo Bo e promosso dal Centro di Ricerca FilPol “Filologia, Politica, Storia, Società”, istituito dagli atenei di Catania, Cagliari, Torino, Urbino e diretto da Stefano Rapisarda. Alle comunicazioni di Giuseppina Brunetti, Filippo Costantini, Paolo Maninchedda, Giuseppe Noto e Stefano Rapisarda, si sono aggiunti i contributi di Alvise Andreose e Antonella Negri, di Antonella Emina e di Paolo Rondinelli, che con i precedenti saggi hanno in comune l’obiettivo di far interagire scienze filologiche e discipline collaterali dando vita ad un’idea di filologia che non si limita alla sua veste di Textkritik, ma che si pone come un dispositivo ermeneutico nel più vasto senso possibile. Nella volontà di percorrere nuove piste d’indagine facendo interagire filologia, dimensione storica, frontiere geografiche e contesti culturali differenti, questo volume dà forma e sostanza ad una riflessione sul ruolo della filologia romanza nella storia e nella cultura europee e globali, all’interno dell’odierna cornice socio-politica