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Article ; Online: The jam session between muscle stem cells and the extracellular matrix in the tissue microenvironment.

Loreti, Mafalda / Sacco, Alessandra

NPJ Regenerative medicine

2022 Volume 7, Issue 1, Page(s) 16

Abstract: Skeletal muscle requires a highly orchestrated coordination between multiple cell types and their microenvironment to exert its function and to maintain its homeostasis and regenerative capacity. Over the past decades, significant advances, including ... ...

Abstract	Skeletal muscle requires a highly orchestrated coordination between multiple cell types and their microenvironment to exert its function and to maintain its homeostasis and regenerative capacity. Over the past decades, significant advances, including lineage tracing and single-cell RNA sequencing, have contributed to identifying multiple muscle resident cell populations participating in muscle maintenance and repair. Among these populations, muscle stem cells (MuSC), also known as satellite cells, in response to stress or injury, are able to proliferate, fuse, and form new myofibers to repair the damaged tissue. These cells reside adjacent to the myofiber and are surrounded by a specific and complex microenvironment, the stem cell niche. Major components of the niche are extracellular matrix (ECM) proteins, able to instruct MuSC behavior. However, during aging and muscle-associated diseases, muscle progressively loses its regenerative ability, in part due to a dysregulation of ECM components. This review provides an overview of the composition and importance of the MuSC microenvironment. We discuss relevant ECM proteins and how their mutations or dysregulation impact young and aged muscle tissue or contribute to diseases. Recent discoveries have improved our knowledge about the ECM composition of skeletal muscle, which has helped to mimic the architecture of the stem cell niche and improved the regenerative capacity of MuSC. Further understanding about extrinsic signals from the microenvironment controlling MuSC function and innovative technologies are still required to develop new therapies to improve muscle repair.
Language	English
Publishing date	2022-02-17
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2057-3995
ISSN (online)	2057-3995
DOI	10.1038/s41536-022-00204-z
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Book ; Online: A Logic for Monitoring Dynamic Networks of Spatially-distributed Cyber-Physical Systems

Nenzi, L. / Bartocci, E. / Bortolussi, L. / Loreti, M.

2021

Abstract: Cyber-Physical Systems (CPS) consist of inter-wined computational (cyber) and physical components interacting through sensors and/or actuators. Computational elements are networked at every scale and can communicate with each other and with humans. Nodes ...

Abstract	Cyber-Physical Systems (CPS) consist of inter-wined computational (cyber) and physical components interacting through sensors and/or actuators. Computational elements are networked at every scale and can communicate with each other and with humans. Nodes can join and leave the network at any time or they can move to different spatial locations. In this scenario, monitoring spatial and temporal properties plays a key role in the understanding of how complex behaviors can emerge from local and dynamic interactions. We revisit here the Spatio-Temporal Reach and Escape Logic (STREL), a logic-based formal language designed to express and monitor spatio-temporal requirements over the execution of mobile and spatially distributed CPS. STREL considers the physical space in which CPS entities (nodes of the graph) are arranged as a weighted graph representing their dynamic topological configuration. Both nodes and edges include attributes modeling physical and logical quantities that can evolve over time. STREL combines the Signal Temporal Logic with two spatial modalities reach and escape that operate over the weighted graph. From these basic operators, we can derive other important spatial modalities such as everywhere, somewhere and surround. We propose both qualitative and quantitative semantics based on constraint semiring algebraic structure. We provide an offline monitoring algorithm for STREL and we show the feasibility of our approach with the application to two case studies: monitoring spatio-temporal requirements over a simulated mobile ad-hoc sensor network and a simulated epidemic spreading model for COVID19. Comment: arXiv admin note: substantial text overlap with arXiv:1904.08847
Keywords	Computer Science - Logic in Computer Science
Subject code	005
Publishing date	2021-05-24
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: A Spatial Logic for Simplicial Models

Loreti, Michele / Quadrini, Michela

2021

Abstract: Collective Adaptive Systems often consist of many heterogeneous components typically organised in groups. These entities interact with each other by adapting their behaviour to pursue individual or collective goals. In these systems, the distribution of ... ...

Abstract	Collective Adaptive Systems often consist of many heterogeneous components typically organised in groups. These entities interact with each other by adapting their behaviour to pursue individual or collective goals. In these systems, the distribution of these entities determines a space that can be either physical or logical. The former is defined in terms of a physical relation among components. The latter depends on logical relations, such as being part of the same group. In this context, specification and verification of spatial properties play a fundamental role in supporting the design of systems and predicting their behaviour. For this reason, different tools and techniques have been proposed to specify and verify the properties of space, mainly described as graphs. Therefore, the approaches generally use model spatial relations to describe a form of proximity among pairs of entities. Unfortunately, these graph-based models do not permit considering relations among more than two entities that may arise when one is interested in describing aspects of space by involving interactions among groups of entities. In this work, we propose a spatial logic interpreted on simplicial complexes. These are topological objects, able to represent surfaces and volumes efficiently that generalise graphs with higher-order edges. We discuss how the satisfaction of logical formulas can be verified by a correct and complete model checking algorithm, which is linear to the dimension of the simplicial complex and logical formula. The expressiveness of the proposed logic is studied in terms of the spatial variants of classical bisimulation and branching bisimulation relations defined over simplicial complexes.
Keywords	Computer Science - Logic in Computer Science
Subject code	005
Publishing date	2021-05-18
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: RobTL

Castiglioni, Valentina / Loreti, Michele / Tini, Simone

A Temporal Logic for the Robustness of Cyber-Physical Systems

2022

Abstract: We propose the Robustness Temporal Logic (RobTL), a novel temporal logic for the specification and analysis of distances between the behaviours of Cyber-Physical Systems (CPSs) over a finite time horizon. Differently from classical temporal logic ... ...

Abstract	We propose the Robustness Temporal Logic (RobTL), a novel temporal logic for the specification and analysis of distances between the behaviours of Cyber-Physical Systems (CPSs) over a finite time horizon. Differently from classical temporal logic expressing properties on the behaviour of a system, we can use RobTL specifications to measure the differences in the behaviours of systems with respect to various objectives and temporal constraints, and to study how those differences evolve in time. Since the behaviour of CPSs is inevitably subject to uncertainties and approximations, we show how the unique features of RobTL allow us to specify property of robustness of systems against perturbations, i.e., their capability to function correctly even under the effect of perturbations. Given the probabilistic nature of CPSs, our model checking algorithm for RobTL specifications is based on statistical inference. As an example of an application of our framework, we consider a supervised, self-coordinating engine system that is subject to attacks aimed at inflicting overstress of equipment.
Keywords	Computer Science - Logic in Computer Science
Subject code	006
Publishing date	2022-12-21
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: REPTILE

Corradini, Flavio / Loreti, Miichele / Piangerelli, Marco / Rocchetti, Giacomo

A Proactive Real-Time Deep Reinforcement Learning Self-adaptive Framework

2022

Abstract: In this work a general framework is proposed to support the development of software systems that are able to adapt their behaviour according to the operating environment changes. The proposed approach, named REPTILE, works in a complete proactive manner ... ...

Abstract	In this work a general framework is proposed to support the development of software systems that are able to adapt their behaviour according to the operating environment changes. The proposed approach, named REPTILE, works in a complete proactive manner and relies on Deep Reinforcement Learning-based agents to react to events, referred as novelties, that can affect the expected behaviour of the system. In our framework, two types of novelties are taken into account: those related to the context/environment and those related to the physical architecture itself. The framework, predicting those novelties before their occurrence, extracts time-changing models of the environment and uses a suitable Markov Decision Process to deal with the real-time setting. Moreover, the architecture of our RL agent evolves based on the possible actions that can be taken.
Keywords	Computer Science - Software Engineering ; Computer Science - Artificial Intelligence
Subject code	006
Publishing date	2022-03-28
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: EvTL

Castiglioni, Valentina / Loreti, Michele / Tini, Simone

A Temporal Logic for the Transient Analysis of Cyber-Physical Systems

2022

Abstract: The behaviour of systems characterised by a closed interaction of software components with the environment is inevitably subject to perturbations and uncertainties. In this paper we propose a general framework for the specification and verification of ... ...

Abstract	The behaviour of systems characterised by a closed interaction of software components with the environment is inevitably subject to perturbations and uncertainties. In this paper we propose a general framework for the specification and verification of requirements on the behaviour of these systems. We introduce the Evolution Temporal Logic (EvTL), a stochastic extension of STL allowing us to specify properties of the probability distributions describing the transient behaviour of systems, and to include the presence of uncertainties in the specification. We equip EvTL with a robustness semantics and we prove it sound and complete with respect to the semantics induced by the evolution metric, i.e., a hemimetric expressing how well a system is fulfilling its tasks with respect to another one. Finally, we develop a statistical model checking algorithm for EvTL specifications. As an example of an application of our framework, we consider a three-tanks laboratory experiment. Comment: arXiv admin note: text overlap with arXiv:2111.15319
Keywords	Computer Science - Logic in Computer Science ; F.3.1
Subject code	004
Publishing date	2022-04-28
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The regulatory proteins DSCR6 and Ezh2 oppositely regulate Stat3 transcriptional activity in mesoderm patterning during

Loreti, Mafalda / Shi, De-Li / Carron, Clémence

The Journal of biological chemistry

2020 Volume 295, Issue 9, Page(s) 2724–2735

Abstract: Embryonic cell fate specification and axis patterning requires integration of several signaling pathways that orchestrate region-specific gene expression. The transcription factor signal transducer and activator of transcription 3 (Stat3) plays important ...

Abstract	Embryonic cell fate specification and axis patterning requires integration of several signaling pathways that orchestrate region-specific gene expression. The transcription factor signal transducer and activator of transcription 3 (Stat3) plays important roles during early development, but it is unclear how Stat3 is activated. Here, using
MeSH term(s)	Animals ; Body Patterning ; Enhancer of Zeste Homolog 2 Protein/physiology ; Gene Expression Regulation, Developmental ; Mesoderm/cytology ; Protein Processing, Post-Translational ; Repressor Proteins/physiology ; STAT3 Transcription Factor/metabolism ; Transcription Factors ; Xenopus/growth & development ; Xenopus Proteins/metabolism ; Xenopus Proteins/physiology
Chemical Substances	RIPPLY3 protein, Xenopus ; Repressor Proteins ; STAT3 Transcription Factor ; Transcription Factors ; Xenopus Proteins ; EZH2 protein, Xenopus (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43)
Language	English
Publishing date	2020-01-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA119.010719
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Book ; Online: Online Monitoring of Spatio-Temporal Properties for Imprecise Signals

Visconti, Ennio / Bartocci, Ezio / Loreti, Michele / Nenzi, Laura

2021

Abstract: From biological systems to cyber-physical systems, monitoring the behavior of such dynamical systems often requires to reason about complex spatio-temporal properties of physical and/or computational entities that are dynamically interconnected and ... ...

Abstract	From biological systems to cyber-physical systems, monitoring the behavior of such dynamical systems often requires to reason about complex spatio-temporal properties of physical and/or computational entities that are dynamically interconnected and arranged in a particular spatial configuration. Spatio-Temporal Reach and Escape Logic (STREL) is a recent logic-based formal language designed to specify and to reason about spatio-temporal properties. STREL considers each system's entity as a node of a dynamic weighted graph representing their spatial arrangement. Each node generates a set of mixed-analog signals describing the evolution over time of computational and physical quantities characterising the node's behavior. While there are offline algorithms available for monitoring STREL specifications over logged simulation traces, here we investigate for the first time an online algorithm enabling the runtime verification during the system's execution or simulation. Our approach extends the original framework by considering imprecise signals and by enhancing the logics' semantics with the possibility to express partial guarantees about the conformance of the system's behavior with its specification. Finally, we demonstrate our approach in a real-world environmental monitoring case study.
Keywords	Computer Science - Logic in Computer Science
Subject code	004
Publishing date	2021-09-16
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: A framework to measure the robustness of programs in the unpredictable environment

Castiglioni, Valentina / Loreti, Michele / Tini, Simone

2021

Abstract: Due to the diffusion of IoT, modern software systems are often thought to control and coordinate smart devices in order to manage assets and resources, and to guarantee efficient behaviours. For this class of systems, which interact extensively with ... ...

Abstract	Due to the diffusion of IoT, modern software systems are often thought to control and coordinate smart devices in order to manage assets and resources, and to guarantee efficient behaviours. For this class of systems, which interact extensively with humans and with their environment, it is thus crucial to guarantee their correct behaviour in order to avoid unexpected and possibly dangerous situations. In this paper we will present a framework that allows us to measure the robustness of systems. This is the ability of a program to tolerate changes in the environmental conditions and preserving the original behaviour. In the proposed framework, the interaction of a program with its environment is represented as a sequence of random variables describing how both evolve in time. For this reason, the considered measures will be defined among probability distributions of observed data. The proposed framework will be then used to define the notions of adaptability and reliability. The former indicates the ability of a program to absorb perturbation on environmental conditions after a given amount of time. The latter expresses the ability of a program to maintain its intended behaviour (up-to some reasonable tolerance) despite the presence of perturbations in the environment. Moreover, an algorithm, based on statistical inference, is proposed to evaluate the proposed metric and the aforementioned properties. We use two case studies to the describe and evaluate the proposed approach.
Keywords	Computer Science - Logic in Computer Science
Subject code	006
Publishing date	2021-11-30
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Qualitative and Quantitative Monitoring of Spatio-Temporal Properties with SSTL

Nenzi, L. / Bortolussi, L. / Ciancia, V. / Loreti, M. / Massink, M.

2017

Abstract: In spatially located, large scale systems, time and space dynamics interact and drives the behaviour. Examples of such systems can be found in many smart city applications and Cyber-Physical Systems. In this paper we present the Signal Spatio-Temporal ... ...

Abstract	In spatially located, large scale systems, time and space dynamics interact and drives the behaviour. Examples of such systems can be found in many smart city applications and Cyber-Physical Systems. In this paper we present the Signal Spatio-Temporal Logic (SSTL), a modal logic that can be used to specify spatio-temporal properties of linear time and discrete space models. The logic is equipped with a Boolean and a quantitative semantics for which efficient monitoring algorithms have been developed. As such, it is suitable for real-time verification of both white box and black box complex systems. These algorithms can also be combined with stochastic model checking routines. SSTL combines the until temporal modality with two spatial modalities, one expressing that something is true somewhere nearby and the other capturing the notion of being surrounded by a region that satisfies a given spatio-temporal property. The monitoring algorithms are implemented in an open source Java tool. We illustrate the use of SSTL analysing the formation of patterns in a Turing Reaction-Diffusion system and spatio-temporal aspects of a large bike-sharing system. Comment: 36 pages with 13 figures
Keywords	Computer Science - Logic in Computer Science ; F.4.1
Subject code	005
Publishing date	2017-06-28
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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