2,545 research outputs found
La metafisica della conoscenza in Sofia Vanni Rovighi e Francesca Rivetti Barbò
No full textNel saggio si evidenziano i punti di continuità prevalenti e le distinzioni nella tecnica e sensibilità espositiva, più che non nella reale sostanza di pensiero, di due tra le maggiori esponenti femminili della filosofia realista del secondo novecento Sofia Vanni Rovighi e Francesca Rivetti Barbò. Entrambe pongono l'accento, per un discorso filosofico alternativo ai paradigmi, prima idealistico e poi postmoderno, sul recupero della importanza metafisica del conoscere e della conseguente ontologia che parta dal " senso e linguaggio comune", entrambe di derivazione neoaristotelica, Entrambe le filosofe valorizzano la modernità con inaspettate aperture al neopositivismo logico e alla filosofia analitica. Il loro comune avversario è l'ontologismo ed il neoparmenidismo di Emanuele Severino. Ma questa polemica si svolge sottotraccia, all'interno di una piana e chiara esposizione della filosofia teoretica, rivolta immediatamente agli studenti e solo di riflesso agli studiosi e filosofi di professione
Reality and Transition: The "Spiritual" Space in Contemporary Italian Fiction
No full textDialogo con Francesca Matteoni, Giulio Mozzi, Paolo Pecere, Vanni Santoni e Alessandro Zaccuri, a cura di Alessandro Raveggi.A conversation with Francesca Matteoni, Giulio Mozzi, Paolo Pecere, Vanni Santoni, and Alessandro Zaccuri, curated by Alessandro Raveggi
A novel class of anti-tumoral compounds, pyrrolonaphtoxazepines (PNOXs), targets the p66Shc/STAT4 axis in CLL prymary cells and reduces tumor burden in Eμ-TCL1 mice
No full textChronic lymphocytic leukemia is an haematological malignancy characterized by the accumulation of CD5+CD19+ mature B cell clones in peripheral blood, spleen, lymph nodes and bone marrow (B-CLL). Leukemic cells accumulation is both dependent upon enhanced B cell receptor (BCR)-driven proliferation and defects in the apoptotic machinery. Additionally, alterations of surface chemokine receptors have been accounted for the enhanced accumulation and survival of CLL cells within the secondary lymphoid organs (SLOs). At present, treatment options for CLL patients include drugs targeting proteins participating in the BCR signaling pathway (i.e Ibrutinib, Idelalisib) and in the apoptotic process (i.e Venetoclax). However, relapsed or refractory CLL is still a clinical problem, and prolonged treatment with the above mentioned drugs leads to resistance occurrence as well as severe side effects, indicating that novel therapeutic options are needed.
The adaptor protein p66Shc is a negative regulator of BCR-signaling and a pro-apoptotic protein whose loss in CLL B cells accounts for the extended survival of tumoral cells and poor prognosis. p66Shc has been also shown to control B cells trafficking by altering CXCR4 function, CCR7 and S1PR1 expression. The pathogenetic role of p66Shc in CLL was recently confirmed in the Eμ-TCL1 mouse model of CLL. Eμ-TCL1 mice lacking the p66Shc gene (Eμ-TCL1p66Shc-/- mice), showed indeed a more severe disease characterized by earlier onset and higher nodal and extranodal accumulation of leukemic cells compared with the Eμ-TCL1 mice. Hence, identification of compounds that up-regulate p66Shc expression and function in malignant B cells are likely to target cell proliferation, migration and apoptosis and may represent an appealing therapeutic option for CLL.
In this study, we decided to investigate the molecular mechanism underlying the anti tumoral efficacy of a recently developed class of compounds, the pyrrolonaphthoxazepines (PNOXs), which have been demonstrated to be effective in vitro in several tumoral cells, including primary human CLL cells and to test, for the first time, these novel compounds in the murine model of human CLL, the Eμ-TCL1 mouse.
Our results show that PNOXs restore p66Shc expression and activate transcription factor STAT4 in primary human CLL cells without affecting normal B cells. Accordingly, our data show that the recovery of p66Shc expression in human CLL cells directly correlates with the apoptosis rate induced by PNOXs. In agreement with human CLL, we found that PNOXs efficiently upregulate p66Shc and promote apoptosis in murine CLL cells. Moreover, we demonstrated that PNOXs were able to activate pro-apoptotic activity of p66Shc through a JNK dependent phosphorylation of Ser36 residue on p66Shc, suggesting that the anti-tumor effect of PNOXs in human CLL cells relies at least in part on its ability to first promote p66Shc expression and subsequently to foster its apoptotic function. PNOXs treatment of Eμ-TCL1 mice resulted in a significantly longer overall survival and in the reduction in tumor burden in the spleen and in the peritoneum. The powerful antitumor effect of PNOXs in vivo correlates with upregulation of S1PR1 and in the mobilization of leukemic cells from the spleen into the blood. Interestingly, treatment with PNOXs compounds on Eμ-TCL1p66Shc-/- mice highlighted that only one compound, PNOX-3, exerts a p66Shc-independent pro-apoptotic activity towards circulating CLL cells, while absence of p66Shc impairs the ability of PNOXs to mobilize CLL cells from the spleen to peripheral blood. Since accumulation of leukemic cells within secondary lymphoid organs is responsible for the enhanced survival of leukemic cells and drug resistance, our data indicate that PNOXs may represent a novel effective treatment for CLL by favouring the mobilization of leukemic cells from the protective tumor microenvironment of the SLOs into the blood and by promoting apoptosis through the upregulation of p66Shc
High-throughput screening of β-secretase inhibitors by multiwell spectroscopic methods
No full text"The love that made hell, paradise." Ouida re-writing the Paolo and Francesca theme in Held in Bondage
No full textThe bestselling Victorian author Ouida reveals in her novels, and, in particular, Held in Bondage, an extraordinary knowledge od Dante, by using characters and themes from the Commedia. The Paolo and Francesca theme actually constitutes part of the plot of the novel and is to be found in many of her other works, short stories and non-fiction writing
HERStory Makers 2023: Francesca Fotheringham
No full textFrancesca Fotheringham is a postdoctoral research associate at the University of Edinburgh studying educational psychology with a focus on neurodiversity. She took part in HERStory Makers 2023.What is HERStory Makers?HERStory Makers is a social media competition for female-identifying early career researchers to share their research, their career journeys, and to inspire the next generation. Winners are selected by public vote. HERStory Makers is also part of EXPLORATHON, Scotland's contribution to European Researchers' Night.In 2022-23, EXPLORATHON Francescasupported by the Engineering & Physical Sciences Research Council [grant number EP/X020762/1].Author contributions to contentFrancesca conceived, planned, and recorded the video content. Kirsty Ross edited the video content to insert HERStory Maker credits, added subtitles, and reduce video length to below Twitter/X limit of 2 mins and 20 secs.</p
Enhancing Supply Chain Resilience: The Impact of 4.0 Technologies
No full textBackground: Every company has a supply chain (SC) and must deal with its uncertainty, which can provoke a bullwhip effect; resilience of SCs is a main characteristic to be achieved. However, studies on the creation of digital SCs adopting Industry 4.0 (I4.0) are very scarce and require more attention. Objectives: Industry 4.0 is very little studied in the field of resilience of SCs, despite the huge benefits it can provide. This study aims to evaluate I4.0 to improve both strategic and operational performance. Method: Initially, a deep literature has been carried out to find out the requirements to improve the resilience of a SC and how I4.0 can contribute. Then, a framework has been developed using Internet of Things (IoT), artificial intelligence (AI), augmented reality (AR) and virtual reality (VR). Results: The resilience of SC is a very new topic, and I4.0 can provide great benefits. The designed framework can improve resilience by integrating new technologies. Conclusion: Adopting I4.0 into the SC can be challenging, but it is mandatory to integrate it to keep competitiveness high and improve the resilience of the company. Internet of Things can collect data, analysed by AI and made available with AR and VR to operators. Contribution: This study helps in closing the gap between the need of resilience in SC and technological solutions based on I4.0. This improves warehousing, inventory management and demand forecasting with distribution communications and information technology
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