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- Pucci, M., et al.
(författare)
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Colorectal cancer-derived small extracellular vesicles induce TGF beta 1-mediated epithelial to mesenchymal transition of hepatocytes
- 2023
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Ingår i: Cancer Cell International. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Metastatic disease is the major cause of cancer-related deaths. Increasing evidence shows that primary tumor cells can promote metastasis by preparing the local microenvironment of distant organs, inducing the formation of the so-called "pre-metastatic niche". In recent years, several studies have highlighted that among the tumor-derived molecular components active in pre-metastatic niche formation, small extracellular vesicles (sEVs) play a crucial role. Regarding liver metastasis, the ability of tumor-derived sEVs to affect the activities of non-parenchymal cells such as Kupffer cells and hepatic stellate cells is well described, while the effects on hepatocytes, the most conspicuous and functionally relevant hepatic cellular component, remain unknown. Methods sEVs isolated from SW480 and SW620 CRC cells and from clinical samples of CRC patients and healthy subjects were used to treat human healthy hepatocytes (THLE-2 cells). RT-qPCR, Western blot and confocal microscopy were applied to investigate the effects of this treatment. Results Our study shows for the first time that TGF beta 1-carrying CRC_sEVs impair the morphological and functional properties of healthy human hepatocytes by triggering their TGF beta 1/SMAD-dependent EMT. These abilities of CRC_sEVs were further confirmed by evaluating the effects elicited on hepatocytes by sEVs isolated from plasma and biopsies from CRC patients. Conclusions Since it is known that EMT of hepatocytes leads to the formation of a fibrotic environment, a well-known driver of metastasis, these results suggest that CRC_sEV-educated hepatocytes could have an active and until now neglected role during liver metastasis formation.
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- Bucchiarone, A., et al.
(författare)
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Gamified and Self-Adaptive Applications for the Common Good : Research Challenges Ahead
- 2021
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Ingår i: Proceedings - 2021 International Symposium on Software Engineering for Adaptive and Self-Managing Systems, SEAMS 2021. - : Institute of Electrical and Electronics Engineers Inc.. - 9781665402897 ; , s. 149-155
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Konferensbidrag (refereegranskat)abstract
- Motivational digital systems offer capabilities to engage and motivate end-users to foster behavioral changes towards a common goal. In general these systems use gamification principles in non-games contexts. Over the years, gamification has gained consensus among researchers and practitioners as a tool to motivate people to perform activities with the ultimate goal of promoting behavioural change, or engaging the users to perform activities that can offer relevant benefits but which can be seen as unrewarding and even tedious. There exists a plethora of heterogeneous application scenarios towards reaching the common good that can benefit from gamification. However, an open problem is how to effectively combine multiple motivational campaigns to maximise the degree of participation without exposing the system to counterproductive behaviours. We conceive motivational digital systems as multi-agent systems: self-adaptation is a feature of the overall system, while individual agents may self-adapt in order to leverage other agents' resources, functionalities and capabilities to perform tasks more efficiently and effectively. Consequently, multiple campaigns can be run and adapted to reach common good. At the same time, agents are grouped into micro-communities in which agents contribute with their own social capital and leverage others' capabilities to balance their weaknesses. In this paper we propose our vision on how the principles at the base of the autonomous and multi-agent systems can be exploited to design multi-challenge motivational systems to engage smart communities towards common goals. We present an initial version of a general framework based on the MAPE-K loop and a set of research challenges that characterise our research roadmap for the implementation of our vision.
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- Bucchiarone, A., et al.
(författare)
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Run-time and Collective Adaptation of Gameful Systems
- 2020
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Ingår i: Proceedings - 2020 IEEE International Conference on Autonomic Computing and Self-Organizing Systems Companion, ACSOS-C 2020. - : Institute of Electrical and Electronics Engineers Inc.. - 9781728184142 ; , s. 145-146
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Konferensbidrag (refereegranskat)abstract
- The term gamification has been introduced in the early 2000s [13] and has as central idea the usage of game elements in non-entertainment application domains to foster motivation [8], [15], [6]. There is a considerable amount of literature concerning gamification concepts [5], [16], related taxonomies [18], [17], and literature reviews [10].
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- Bucchiarone, A., et al.
(författare)
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Towards a Framework to Assist Iterative and Adaptive Design in Gameful Systems
- 2021
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Ingår i: Proceedings - 2021 36th IEEE/ACM International Conference on Automated Software Engineering Workshops, ASEW 2021. - : Institute of Electrical and Electronics Engineers Inc.. - 9781665435833 ; , s. 78-84
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Konferensbidrag (refereegranskat)abstract
- Over the years, gamification gained consensus among researchers and practitioners as a tool to motivate people to perform activities deemed as tedious or unexciting. Hence, there exist many and heterogeneous application domains that may benefit from gamification. However, the domain expert and the designer are often separate individuals with dissimilar backgrounds, skills, and understanding. Thus, they need a shared language to communicate and to design a gamified system in line with its ultimate goal, the implementation of which can then be left to the developers. While several studies from the literature tackled the problem of formally defining a design language able to assist designers in the code production, they rarely foresee a framework capable to include all the involved stakeholders (e.g., domain experts). Moreover, it is essential to allow those stakeholders to monitor the gameplay at runtime and intervene when necessary, as the design process is intrinsically iterative. In this work, we present a design framework that models the whole life cycle of gamification solutions, from the design to the execution and monitoring of the system. Finally, we present a prototype of the framework implemented in the Education domain.
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- Nuno, E., et al.
(författare)
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Rendezvous of Nonholonomic Robots via Output-Feedback Control Under Time-Varying Delays
- 2022
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Ingår i: IEEE Transactions on Control Systems Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 1063-6536 .- 1558-0865. ; , s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- We address the problem of making nonholonomic vehicles, with second-order dynamics and interconnected over a bidirectional network, converge to a formation centered at a nonprespecified point on the plane with a nonprespecified common orientation. We assume that only the Cartesian position of the center of mass of each vehicle and its orientation are available for measurement, but not the velocities. In addition, we assume that the interconnections are affected by time-varying delays. Our control method consists in designing a set of second-order systems that are interconnected with the robots' dynamics through virtual springs and transmit their own coordinates to achieve consensus. This and the virtual elastic couplings with the vehicles make the latter achieve consensus too. To the best of our knowledge, output-feedback consensus control of underactuated nonholonomic vehicles has been little studied, all the less in the presence of delays.
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- Shen, Ruidan, et al.
(författare)
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Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
- 2022
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Ingår i: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 13:45, s. 13524-13540
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Tidskriftsartikel (refereegranskat)abstract
- Protein tyrosine phosphatases (PTPs) possess a conserved mobile catalytic loop, the WPD-loop, which brings an aspartic acid into the active site where it acts as an acid/base catalyst. Prior experimental and computational studies, focused on the human enzyme PTP1B and the PTP from Yersinia pestis, YopH, suggested that loop conformational dynamics are important in regulating both catalysis and evolvability. We have generated a chimeric protein in which the WPD-loop of YopH is transposed into PTP1B, and eight chimeras that systematically restored the loop sequence back to native PTP1B. Of these, four chimeras were soluble and were subjected to detailed biochemical and structural characterization, and a computational analysis of their WPD-loop dynamics. The chimeras maintain backbone structural integrity, with somewhat slower rates than either wild-type parent, and show differences in the pH dependency of catalysis, and changes in the effect of Mg2+. The chimeric proteins' WPD-loops differ significantly in their relative stability and rigidity. The time required for interconversion, coupled with electrostatic effects revealed by simulations, likely accounts for the activity differences between chimeras, and relative to the native enzymes. Our results further the understanding of connections between enzyme activity and the dynamics of catalytically important groups, particularly the effects of non-catalytic residues on key conformational equilibria.
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