Archivio istituzionale della ricerca - Alma Mater Studiorum Università di Bologna
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Targeting α4β1 integrin: from cyclic to linear ligands, effects of chemical modifications
No full textThe immune system depends on integrins for adhesion and migration during leukocyte trafficking and for intracellular signalling. There is a causal relationship between dysregulation of integrin expression and the onset of pathological conditions, such as autoimmune diseases, inflammation, cancer, and infections. Therefore, integrins, such as α4β1, are considered important therapeutic targets. In this study, a series of novel compounds were synthesized and evaluated for affinity and potency towards α4β1, and selectivity towards α5β1, and αMβ2 integrins. Three compounds 3, 4, and 8 showed excellent binding affinities (Ki < 10 nM) for α4β1. In cell adhesion assays these three ligands behaved as antagonists of α4β1, as confirmed by integrin-mediated intracellular signalling with a functional selectivity over ERK1/2 signalling pathway. Notably, compound 4, a proline derivative, was an antagonist against α4β1 (IC50 15 ± 3 nM) and an agonist against αMβ2 integrin (EC50 23 ± 5 nM). Compound 2, a fluorinated β-lactam derivative, was a selective and potent agonist of α5β1 (EC50 45.98 ± 7.92 nM). Compound 5, although it seems to bind to a different site compared to LDV in α4β1 integrin, showed an agonist behaviour in cell adhesion mediated by α4β1 and α5β1 integrin (EC50 25 ± 3 and 4.8 ± 3.4 nM, respectively) and in activating α4β1 integrin-mediated ERK1/2 and Akt phosphorylation. Compound 8 was the most potent agonist of the series against αMβ2 (EC50 1.4 ± 0.2 nM). Overall, the present study provides new insights into the effects of new integrin ligands that could be considered as potential lead compounds for therapeutic applications in inflammatory diseases and cancer
A Novel 3D Printed Multi-Material Simulator for Endoscopic Stapes Surgery: The “3D Stapes Trainer”
Get PDFObjective To develop and preliminarily validate a 3D-printed, multi-material, patient-specific simulator of the external and middle ear affected by stapes fixation. The simulator was designed for training in endoscopic stapes surgery (SS), addressing the lack of reliable training platforms for this technically challenging procedure.Methods Imaging data from a CT scan of a patient were used to create a virtual 3D model of significant ear structures. The simulator consisted of a multi-use temporal bone holder and a single-use middle ear box, printed with material Jetting 3D printing technology. Eight participants to a university ear surgery course used the simulator to perform endoscopic stapes surgery. The surgical performance was evaluated using modified Objective Structured Assessment of Technical Skills (OSATS) scoring, and participant feedback was gathered through qualitative questionnaires.Results Seven of the eight participants successfully completed the simulated SS, with a mean surgical time of 24 min. OSATS scores showed acceptable performance, with 75% of participants achieving a score above 20. The tactile feedback, particularly for the stapes fixation, was well received, although the chorda tympani was deemed too fragile. The simulator was highly valued for visuomotor coordination development.Conclusions The 3D Stapes Trainer represents a promising platform for training in endoscopic SS. Despite its limitations, the model provided young surgeons with a valuable platform to gain confidence in the steps of endoscopic SS, offering a high-fidelity simulation that contributes to the development of the technical skills required in this demanding procedure.Level of Evidence N/
Acute limb ischemia after occluded femoro-popliteal stents: a comparative analysis between endovascular revascularization vs. open bypass (FOCUS Study)
No full textBackground: The aim of the study was to compare the early and medium-term outcomes of endovascular revascularization versus bypass for the treatment of occluded femoro-popliteal stents in patients with acute limb ischemia (ALI) (insights of the OUT-STEPP multicentric registry). Methods: Between January 2016 and December 2021, 317 patients in 14 centers underwent treatment for symptomatic femoro-popliteal In-Stent Occlusion (ISO). Sixty patients with ALI were included into the present study: 42 (70%) underwent endovascular revascularization (Group ENDO), and 18 (30%) underwent open bypass surgery (Group OPEN). Early (30 days) results were assessed and compared between the two groups. Estimated 5-year outcomes were evaluated and compared with the log-rank test. Results: At 30 days no differences were found in terms of Major Adverse Cardiovascular Events (MACEs), acute kidney injury, reintervention(s), major amputation, and all-cause mortality between the two groups. The need for blood transfusions was similar in both groups (Group OPEN 7, 38.9% vs. Group ENDO 13, 30.1%; P=0.14). The mean length of hospital stay was higher for patients in Group OPEN (11.3±6.5 vs. 4.4±1.9 days; P<0.001). The overall median duration of follow-up was 35 (IQR 13-55.75) months. At 5 years there were no differences between the two groups in terms of survival (69.8% Group OPEN vs. 64.6% Group ENDO; P=0.76, log-rank 0.09), overall patency (71.4% Group OPEN vs. 72.8% Group ENDO; P=0.56, log-rank 0.34), freedom from reintervention(s) (76% Group OPEN vs. 63.4% Group ENDO; P=0.32, log-rank 0.99), and amputation-free survival (88.1% Group OPEN vs. 83.4% Group ENDO; P=0.76, log-rank 0.09). Conclusions: Endovascular revascularization and bypass seem to provide effective flow restoration in patients with ALI due to femoro-popliteal ISO. Open surgery was associated with longer hospital stay. At 5 years, no significant differences were found between the two groups in terms of overall patency, need for reintervention(s), and amputation-free survival, even though further studies on a larger sample size and potentially prospective will be necessary to validate these preliminary findings
Do networks get emotional? The role of leaders’ emotions for (network) success
No full textEmotions are an important component of human life, influencing dyadic and organization-wide interactions. More specifically, leaders’ emotions affect positively and negatively not only their followers, but also organizational and group outcomes. Through a multiple case study of four collaborative governance networks, this paper explores whether and how leaders’ emotions influence network success. The results show that the emotional states that leaders bring into the network seem to influence its functioning: positive emotions seem to propel its activities and outcomes; negative emotions appear to curb them. Emotions seem also to interact with network identity and trust in affecting network success
Uncovering the protective role of lipid droplet accumulation against acid-induced oxidative stress and cell death in osteosarcoma
No full textExtracellular acidosis stemming from altered tumor metabolism promotes cancer progression by enabling tumor cell adaptation to the hostile microenvironment. In osteosarcoma, we have previously shown that acidosis increases tumor cell survival alongside substantial lipid droplet accumulation. In this study, we explored the role of lipid droplet formation in mitigating cellular stress induced by extracellular acidosis in osteosarcoma cells, thereby enhancing tumor survival during progression. Specifically, we examined how lipid droplets shield against reactive oxygen species induced by extracellular acidosis. We demonstrated that lipid droplet biogenesis is critical for acid-exposed tumor cell survival, as it starts shortly after acid exposure (24 h) and inversely correlates with ROS levels (DCFH-DA assay), lipid peroxidation (Bodipy assay), and the antioxidant response, as also revealed by NRF2 transcript. Additionally, extracellular metabolites, such as lactate, and interaction with mesenchymal stromal cells within the tumor microenvironment intensify lipid droplet build-up in osteosarcoma cells. Critically, upon targeting two key proteins implicated in LD formation - PLIN2 and DGAT1 - cell viability significantly declined while ROS production escalated. In summary, our findings underscore the vital reliance of acid-exposed tumor cells on lipid droplet formation to scavenge oxidative stress. We conclude that the rewiring of lipid metabolism driven by microenvironmental cues is of paramount importance for the survival of metabolically altered osteosarcoma cells in acidic condition. Overall, we suggest that targeting key members of lipid droplet biogenesis may eradicate more aggressive and resistant tumor cells, uncovering potential new treatment strategies for osteosarcoma
A geometry projection method for the topology optimization of additively manufactured variable-stiffness composite laminates
Get PDFContinuous fiber fused filament fabrication (CF4) is a layer-by-layer additive manufacturing technique that deposits continuous fiber fused filaments (CFFFs) with a significant in-plane variation of the fiber trajectory, thereby offering great flexibility in fabricating variable-stiffness composite laminates (VSCLs). We introduce a topology optimization method for the design of additively manufactured VSCLs made of overlapping, fiber-reinforced bars. The proposed method is based on geometry projection (GP) techniques, whereby the bars are represented by high-level geometric primitives. As in other GP techniques, this high-level parameterization is mapped onto a fixed structured finite element mesh for conducting analysis, as in density-based topology optimization techniques. However, unlike previous GP techniques that have demonstrated their applicability in designing structures as assemblies of individual fiber-reinforced components, this work focuses on the design of composite structures that adhere to CF4 manufacturing processes. Therefore, we first formulate a material interpolation scheme that better captures the stiffness at the composite’s joints obtained from bar overlaps as a stack. Second, the proposed material interpolation employs composite laminate theory to capture the in-plane and out-of-plane behavior of the structure. Third, to produce designs that conform to the CF4 process, we also proposed a novel length constraint formulation in the form of penalization on the projection scheme, which ensures a minimum length for all the bars. This minimum length limit does not require adding a constraint to the optimization problem. The efficacy and efficiency of the proposed method are demonstrated by a series of compliance minimization problems with in-plane and/or out-of-plane loading. The methodology is also applied to the design of a displacement inverter compliant mechanism
The ATLAS of Italian Digital Humanities: a dynamic knowledge graph of digital scholarly research on Italian Cultural Heritage
No full textThe goal of the ATLAS is to create a knowledge graph of the international scholarly research on Italian Cultural Heritage leveraged in a Web portal that fosters users’ interpretation and engagement. The Atlas aims to collect, enrich, and provide information extracted from online resources produced in the international academic context, such as digital textual corpora and editions (mostly based on the TEI/XML standard) as well as datasets following Linked Open Data principles and databases, but also ontologies and tools adopted in the community. The ATLAS leverages existing digital heritage resources to develop an innovative system wherein scholarly projects are reused in new non-native environments.
Digital Humanities (DH) is a research field focused on the realisation of Web-based projects wherein to collect authoritative data related to our heritage. However, research outputs are often not easy to discover, and risk obsolescence if not well documented and based on shared guidelines and standards. Moreover, projects are often self-referential, do not follow metadata standards and best practices, and users’ experience is limited in exploration, since interlinking and explanations - including contradictory statements or disagreement - are missing.
In this project we want to show the potential deriving from having shared protocols, good practices, guidelines and evaluation frameworks in the Humanities. In order to tackle these problems in real-world scenarios, a pool of selected sources will be harvested, mined, and reengineered with state-of-the-art Semantic Web technologies and Natural Language Processing methods to define guidelines for excellent projects and create a golden set of reference projects in the Digital Humanities. The aim is to collect sources that are published according to shareable criteria, that can be easily mined to extract research topics, inter and intra-textual relations between sources, as well as bibliographic, literary, and thematic data. Data extracted will be reconciled with international authority records (e.g. VIAF) and open data sources (e.g. Wikidata) to facilitate reuse and the development of mashup applications. Finally, enhanced data will be preserved and leveraged in a dedicated platform to support exploration and discovery of the landscape of DH projects, and will provide suggestions on tools and resources to scholars that are planning new projects. The semantics added to mined data will guarantee knowledge discovery and a correct reuse of resources in new projects.
The ATLAS Web platform will advance the state of the art of DH research by fostering FAIRness of humanities research data, increasing their findability, and reusability, while allowing scholars, teachers, and students to perform data-driven research on high-quality scholarly data. New digital resources will be admitted into the Atlas on the basis of a peer review process. Criteria will be formalised in guidelines, protocols, and tutorials
"Where are the LGBT victims of intimate partner violence? Agencies, operational practices, and interventions who support victims, prevent, and fight against the phenomenon".
No full textThe topic of the project is the intimate partner violence in LGBT relationships and it was chosen by the partners because it was considered that the epistemic notion of curiosity is a valuable tool for sociological interpretation (Bineth,2021) to increase, on the one hand, knowledge of the international literature on the subject, and, on the other hand, to analyze in particular the characteristics and dynamics of this violence, the type of responses by services and listen to the victims. The final aim is to share a compendium of guidelines with a summary of the available regulatory instruments, practices and interventions made by the services/associations involved in the research. This is because, among the LGBT community, the difficulties experienced when attempts are made to know more about the phenomenon, to acquire a greater awareness of the victimization, and to find assistance in case of violence, seem to be more important than in cases of male-to-female IPV (Intimate Partner Violence).Research activities will be based on qualitative analysis techniques (text analysis, semi-structured interviews, life history interviews, and focus groups)
“The marsh did not confine them but defined them”. An Ecocritical Analysis of Waterscapes in Contemporary Anglophone Environmental Narratives
No full textThe history of humankind is entrenched in a broad system of physical, intellectual, and affective interconnections that includes the other-than-human aquatic ecosystems. Both soothing and destructive, hospitable and dangerous, transparent and obscure, water reveals its poiesis in contemporary environmental narratives. While saltwater locations have received substantial attention in critical ocean studies, freshwater literary ecosystems are still significantly underexplored. This article seeks to broaden the scope of the Blue Humanities field and investigate the peculiar freshwater system of wetlands and marshes. By providing an ecocritical analysis of the novels The Hungry Tide (Ghosh, 2004) and Where the Crawdads Sing (Owens, 2018), the article will argue that wetlands and marshes serve metonymically as heterotopic spaces where inter- and intra-specific differences intersect and merge, and where both physical and symbolic boundaries are crossed. Wetlands and marshes foster collective identity, support unconventional gender identities, and serve as spaces for relational thinking, self-development, and resilience
From one crisis to another: the European central bank’s role from the great recession to the Ukraine war
Get PDFThe paper examines the changing role of the European Central Bank over the last
15 years and holds that the ECB has gone through a process of learning by doing,
relying on earlier crisis experiences in forming its response to successive crises.
This learning process has enabled it to sustain the euro countries against various
exogenous shocks both within the power of its mandate and beyond it, implementing
novel reforms. We argue, in fact, that crises stimulated institutional innovations such
as the introduction of Eurozone banking supervision and the European Banking
Union. The latter was a particularly ground-breaking idea, not contemplated by the
Treaties, and addressed to exceptional endogenous dynamics. During the last two
emergencies, triggered by the pandemic and the war, the ECB seems finally to have
learned how to manage crises via a synergic use of available tools