S. Sinisi, V. Alimguzhin, T. Mancini, E. Tronci, F. Mari, and B. Leeners. "Optimal Personalised Treatment Computation through In Silico Clinical Trials on Patient Digital Twins." Fundamenta Informaticae 174 (2020): 283–310. IOS Press. ISSN: 1875-8681. DOI: 10.3233/FI-2020-1943.
Abstract: In Silico Clinical Trials (ISCT), i.e. clinical experimental campaigns carried out by means of computer simulations, hold the promise to decrease time and cost for the safety and efficacy assessment of pharmacological treatments, reduce the need for animal and human testing, and enable precision medicine. In this paper we present methods and an algorithm that, by means of extensive computer simulation-based experimental campaigns (ISCT) guided by intelligent search, optimise a pharmacological treatment for an individual patient (precision medicine ). We show the effectiveness of our approach on a case study involving a real pharmacological treatment, namely the downregulation phase of a complex clinical protocol for assisted reproduction in humans.
Keywords: Artificial Intelligence; Virtual Physiological Human; In Silico Clinical Trials; Simulation; Personalised Medicine; In Silico Treatment Optimisation
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Q. M. Chen, A. Finzi, T. Mancini, I. Melatti, and E. Tronci. "MILP, Pseudo-Boolean, and OMT Solvers for Optimal Fault-Tolerant Placements of Relay Nodes in Mission Critical Wireless Networks." Fundamenta Informaticae 174 (2020): 229–258. IOS Press. ISSN: 1875-8681. DOI: 10.3233/FI-2020-1941.
Abstract: In critical infrastructures like airports, much care has to be devoted in protecting radio communication networks from external electromagnetic interference. Protection of such mission-critical radio communication networks is usually tackled by exploiting radiogoniometers: at least three suitably deployed radiogoniometers, and a gateway gathering information from them, permit to monitor and localise sources of electromagnetic emissions that are not supposed to be present in the monitored area. Typically, radiogoniometers are connected to the gateway through relay nodes . As a result, some degree of fault-tolerance for the network of relay nodes is essential in order to offer a reliable monitoring. On the other hand, deployment of relay nodes is typically quite expensive. As a result, we have two conflicting requirements: minimise costs while guaranteeing a given fault-tolerance. In this paper, we address the problem of computing a deployment for relay nodes that minimises the overall cost while at the same time guaranteeing proper working of the network even when some of the relay nodes (up to a given maximum number) become faulty (fault-tolerance ). We show that, by means of a computation-intensive pre-processing on a HPC infrastructure, the above optimisation problem can be encoded as a 0/1 Linear Program, becoming suitable to be approached with standard Artificial Intelligence reasoners like MILP, PB-SAT, and SMT/OMT solvers. Our problem formulation enables us to present experimental results comparing the performance of these three solving technologies on a real case study of a relay node network deployment in areas of the Leonardo da Vinci Airport in Rome, Italy.
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S. Fischer, R. Ehrig, S. Schaefer, E. Tronci, T. Mancini, M. Egli, F. Ille, T. H. C. Krueger, B. Leeners, and S. Roeblitz. "Mathematical Modeling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation." Frontiers in Endocrinology 12 (2021): 117. ISSN: 1664-2392. DOI: 10.3389/fendo.2021.613048.
Abstract: New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts (“waves”) of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle.
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I. Melatti, F. Mari, T. Mancini, M. Prodanovic, and E. Tronci. "A Two-Layer Near-Optimal Strategy for Substation Constraint Management via Home Batteries." IEEE Transactions on Industrial Electronics (2021): 1. Notes: To appear. DOI: 10.1109/TIE.2021.3102431.
Abstract: Within electrical distribution networks, substation constraints management requires that aggregated power demand from residential users is kept within suitable bounds. Efficiency of substation constraints management can be measured as the reduction of constraints violations w.r.t. unmanaged demand. Home batteries hold the promise of enabling efficient and user-oblivious substation constraints management. Centralized control of home batteries would achieve optimal efficiency. However, it is hardly acceptable by users, since service providers (e.g., utilities or aggregators) would directly control batteries at user premises. Unfortunately, devising efficient hierarchical control strategies, thus overcoming the above problem, is far from easy. We present a novel two-layer control strategy for home batteries that avoids direct control of home devices by the service provider and at the same time yields near-optimal substation constraints management efficiency. Our simulation results on field data from 62 households in Denmark show that the substation constraints management efficiency achieved with our approach is at least 82% of the one obtained with a theoretical optimal centralized strategy.
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T. Mancini, I. Melatti, and E. Tronci. "Any-horizon uniform random sampling and enumeration of constrained scenarios for simulation-based formal verification." IEEE Transactions on Software Engineering (2021): 1. ISSN: 1939-3520. Notes: To appear. DOI: 10.1109/TSE.2021.3109842.
Abstract: Model-based approaches to the verification of non-terminating Cyber-Physical Systems (CPSs) usually rely on numerical simulation of the System Under Verification (SUV) model under input scenarios of possibly varying duration, chosen among those satisfying given constraints. Such constraints typically stem from requirements (or assumptions) on the SUV inputs and its operational environment as well as from the enforcement of additional conditions aiming at, e.g., prioritising the (often extremely long) verification activity, by, e.g., focusing on scenarios explicitly exercising selected requirements, or avoiding </i>vacuity</i> in their satisfaction. In this setting, the possibility to efficiently sample at random (with a known distribution, e.g., uniformly) within, or to efficiently enumerate (possibly in a uniformly random order) scenarios among those satisfying all the given constraints is a key enabler for the practical viability of the verification process, e.g., via simulation-based statistical model checking. Unfortunately, in case of non-trivial combinations of constraints, iterative approaches like Markovian random walks in the space of sequences of inputs in general fail in extracting scenarios according to a given distribution (e.g., uniformly), and can be very inefficient to produce at all scenarios that are both legal (with respect to SUV assumptions) and of interest (with respect to the additional constraints). For example, in our case studies, up to 91% of the scenarios generated using such iterative approaches would need to be neglected. In this article, we show how, given a set of constraints on the input scenarios succinctly defined by multiple finite memory monitors, a data structure (scenario generator) can be synthesised, from which any-horizon scenarios satisfying the input constraints can be efficiently extracted by (possibly uniform) random sampling or (randomised) enumeration. Our approach enables seamless support to virtually all simulation-based approaches to CPS verification, ranging from simple random testing to statistical model checking and formal (i.e., exhaustive) verification, when a suitable bound on the horizon or an iterative horizon enlargement strategy is defined, as in the spirit of bounded model checking.
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Vadim Alimguzhin, Federico Mari, Igor Melatti, Ivano Salvo, and Enrico Tronci. "On Model Based Synthesis of Embedded Control Software." In Proceedings of the 12th International Conference on Embedded Software, EMSOFT 2012, part of the Eighth Embedded Systems Week, ESWeek 2012, Tampere, Finland, October 7-12, 2012, edited by Ahmed Jerraya and Luca P. Carloni and Florence Maraninchi and John Regehr, 227–236. ACM, 2012. Notes: Techreport version can be found at arxiv.org. DOI: 10.1145/2380356.2380398.
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Vadim Alimguzhin, Federico Mari, Igor Melatti, Ivano Salvo, and Enrico Tronci. "Automatic Control Software Synthesis for Quantized Discrete Time Hybrid Systems." In Proceedings of the 51th IEEE Conference on Decision and Control, CDC 2012, December 10-13, 2012, Maui, HI, USA, 6120–6125. IEEE, 2012. Notes: Techreport version can be found at http://arxiv.org/abs/1207.4098. DOI: 10.1109/CDC.2012.6426260.
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Igor Melatti, Robert Palmer, Geoffrey Sawaya, Yu Yang, Robert Mike Kirby, and Ganesh Gopalakrishnan. "Parallel and Distributed Model Checking in Eddy." In Model Checking Software, 13th International SPIN Workshop, Vienna, Austria, March 30 – April 1, 2006, Proceedings, edited by A. Valmari, 108–125. Lecture Notes in Computer Science 3925. Springer - Verlag, 2006. ISSN: 0302-9743. DOI: 10.1007/11691617_7.
Abstract: Model checking of safety properties can be scaled up by pooling the CPU and memory resources of multiple computers. As compute clusters containing 100s of nodes, with each node realized using multi-core (e.g., 2) CPUs will be widespread, a model checker based on the parallel (shared memory) and distributed (message passing) paradigms will more efficiently use the hardware resources. Such a model checker can be designed by having each node employ two shared memory threads that run on the (typically) two CPUs of a node, with one thread responsible for state generation, and the other for efficient communication, including (i) performing overlapped asynchronous message passing, and (ii) aggregating the states to be sent into larger chunks in order to improve communication network utilization. We present the design details of such a novel model checking architecture called Eddy. We describe the design rationale, details of how the threads interact and yield control, exchange messages, as well as detect termination. We have realized an instance of this architecture for the Murphi modeling language. Called Eddy_Murphi, we report its performance over the number of nodes as well as communication parameters such as those controlling state aggregation. Nearly linear reduction of compute time with increasing number of nodes is observed. Our thread task partition is done in such a way that it is modular, easy to port across different modeling languages, and easy to tune across a variety of platforms.
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Federico Mari, Igor Melatti, Ivano Salvo, and Enrico Tronci. "Undecidability of Quantized State Feedback Control for Discrete Time Linear Hybrid Systems." In Theoretical Aspects of Computing – ICTAC 2012, edited by A. Roychoudhury and M. D'Souza, 243–258. Lecture Notes in Computer Science 7521. Springer Berlin Heidelberg, 2012. DOI: 10.1007/978-3-642-32943-2_19.
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Vadim Alimguzhin, Federico Mari, Igor Melatti, Ivano Salvo, and Enrico Tronci. "On-the-Fly Control Software Synthesis." In Proceedings of International SPIN Symposium on Model Checking of Software (SPIN 2013), 61–80. Lecture Notes in Computer Science 7976. Springer - Verlag, 2013. ISSN: 0302-9743. DOI: 10.1007/978-3-642-39176-7_5.
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