| Records |
Author  |
Sinisi, S.; Alimguzhin, V.; Mancini, T.; Tronci, E.; Leeners, B. |
| Title |
Complete populations of virtual patients for in silico clinical trials |
Type |
Journal Article |
| Year |
2021 |
Publication |
Bioinformatics |
Abbreviated Journal |
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Issue |
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Pages |
1-8 |
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| Abstract |
Model-based approaches to safety and efficacy assessment of pharmacological drugs, treatment strategies, or medical devices (In Silico Clinical Trial, ISCT) aim to decrease time and cost for the needed experimentations, reduce animal and human testing, and enable precision medicine. Unfortunately, in presence of non-identifiable models (e.g., reaction networks), parameter estimation is not enough to generate complete populations of Virtual Patient (VPs), i.e., populations guaranteed to show the entire spectrum of model behaviours (phenotypes), thus ensuring representativeness of the trial.We present methods and software based on global search driven by statistical model checking that, starting from a (non-identifiable) quantitative model of the human physiology (plus drugs PK/PD) and suitable biological and medical knowledge elicited from experts, compute a population of VPs whose behaviours are representative of the whole spectrum of phenotypes entailed by the model (completeness) and pairwise distinguishable according to user-provided criteria. This enables full granularity control on the size of the population to employ in an ISCT, guaranteeing representativeness while avoiding over-representation of behaviours.We proved the effectiveness of our algorithm on a non-identifiable ODE-based model of the female Hypothalamic-Pituitary-Gonadal axis, by generating a population of 4 830 264 VPs stratified into 7 levels (at different granularity of behaviours), and assessed its representativeness against 86 retrospective health records from Pfizer, Hannover Medical School and University Hospital of Lausanne. The datasets are respectively covered by our VPs within Average Normalised Mean Absolute Error of 15%, 20%, and 35% (90% of the latter dataset is covered within 20% error). |
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1367-4803 |
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MCLab @ davi @ ref10.1093/bioinformatics/btaa1026 |
Serial |
182 |
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| Author |
Sinisi, S.; Alimguzhin, V.; Mancini, T.; Tronci, E. |
| Title |
Reconciling interoperability with efficient Verification and Validation within open source simulation environments |
Type |
Journal Article |
| Year |
2021 |
Publication |
Simulation Modelling Practice and Theory |
Abbreviated Journal |
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Issue |
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Pages |
102277 |
| Keywords |
Simulation, Verification and Validation, Interoperability, FMI/FMU, Model Exchange, Cyber-Physical Systems |
| Abstract |
A Cyber-Physical System (CPS) comprises physical as well as software subsystems. Simulation-based approaches are typically used to support design and Verification and Validation (V&V) of CPSs in several domains such as: aerospace, defence, automotive, smart grid and healthcare. Accordingly, many simulation-based tools are available to support CPS design. This, on one side, enables designers to choose the toolchain that best suits their needs, on the other side poses huge interoperability challenges when one needs to simulate CPSs whose subsystems have been designed and modelled using different toolchains. To overcome such an interoperability problem, in 2010 the Functional Mock-up Interface (FMI) has been proposed as an open standard to support both Model Exchange (ME) and Co-Simulation (CS) of simulation models created with different toolchains. FMI has been adopted by several modelling and simulation environments. Models adhering to such a standard are called Functional Mock-up Units (FMUs). Indeed FMUs play an essential role in defining complex CPSs through, e.g., the System Structure and Parametrization (SSP) standard. Simulation-based V&V of CPSs typically requires exploring different simulation scenarios (i.e., exogenous input sequences to the CPS under design). Many such scenarios have a shared prefix. Accordingly, to avoid simulating many times such shared prefixes, the simulator state at the end of a shared prefix is saved and then restored and used as a start state for the simulation of the next scenario. In this context, an important FMI feature is the capability to save and restore the internal FMU state on demand. This is crucial to increase efficiency of simulation-based V&V. Unfortunately, the implementation of this feature is not mandatory and it is available only within some commercial software. As a result, the interoperability enabled by the FMI standard cannot be fully exploited for V&V when using open-source simulation environments. This motivates developing such a feature for open-source CPS simulation environments. Accordingly, in this paper, we focus on JModelica, an open-source modelling and simulation environment for CPSs based on an open standard modelling language, namely Modelica. We describe how we have endowed JModelica with our open-source implementation of the FMI 2.0 functions needed to save and restore internal states of FMUs for ME. Furthermore, we present experimental results evaluating, through 934 benchmark models, correctness and efficiency of our extended JModelica. Our experimental results show that simulation-based V&V is, on average, 22 times faster with our get/set functionality than without it. |
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1569-190x |
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MCLab @ davi @ Sinisi2021102277 |
Serial |
186 |
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| Author |
Pugliese, Rosario; Tronci, Enrico |
| Title |
Automatic Verification of a Hydroelectric Power Plant |
Type |
Conference Article |
| Year |
1996 |
Publication |
Third International Symposium of Formal Methods Europe (FME), Co-Sponsored by IFIP WG 14.3 |
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Pages |
425-444 |
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We analyze the specification of a hydroelectric power plant by ENEL (the Italian Electric Company). Our goal is to show that for the specification of the plant (its control system in particular) some given properties hold. We were provided with an informal specification of the plant. From such informal specification we wrote a formal specification using the CCS/Meije process algebra formalism. We defined properties using μ-calculus. Automatic verification was carried out using model checking. This was done by translating our process algebra definitions (the model) and μ-calculus formulas into BDDs. In this paper we present the informal specification of the plant, its formal specification, some of the properties we verified and experimental results. |
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Springer |
Place of Publication |
Oxford, UK |
Editor |
Gaudel, M.-C.; Woodcock, J. |
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Lecture Notes in Computer Science |
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| Series Volume |
1051 |
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3-540-60973-3 |
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yes |
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Sapienza @ mari @ fme96 |
Serial |
53 |
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| Author |
Piperno, Adolfo; Tronci, Enrico |
| Title |
Regular Systems of Equations in λ-calculus |
Type |
Journal Article |
| Year |
1990 |
Publication |
Int. J. Found. Comput. Sci. |
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1 |
Issue |
3 |
Pages |
325-340 |
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Many problems arising in equational theories like Lambda-calculus and Combinatory Logic can be expressed by combinatory equations or systems of equations. However, the solvability problem for an arbitrarily given class of systems is in general undecidable. In this paper we shall focus our attention on a decidable class of systems, which will be called regular systems, and we shall analyse some classical problems and well-known properties of Lambda-calculus that can be described and solved by means of regular systems. The significance of such class will be emphasized showing that for slight extensions of it the solvability problem turns out to be undecidable. |
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yes |
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Sapienza @ mari @ ijfcs90 |
Serial |
60 |
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| Author |
Piperno, Adolfo; Tronci, Enrico |
| Title |
Regular Systems of Equations in λ-calculus |
Type |
Conference Article |
| Year |
1989 |
Publication |
Ictcs |
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Many problems arising in equational theories like Lambda-calculus and Combinatory Logic can be expressed by combinatory equations or systems of equations. However, the solvability problem for an arbitrarily given class of systems is in general undecidable. In this paper we shall focus our attention on a decidable class of systems, which will be called regular systems, and we shall analyse some classical problems and well-known properties of Lambda-calculus that can be described and solved by means of regular systems. The significance of such class will be emphasized showing that for slight extensions of it the solvability problem turns out to be undecidable. |
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Mantova - Italy |
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yes |
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Sapienza @ mari @ ictcs89 |
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61 |
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| Author |
Pappagallo, A.; Massini, A.; Tronci, E. |
| Title |
Monte Carlo Based Statistical Model Checking of Cyber-Physical Systems: A Review |
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Journal Article |
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2020 |
Publication |
Information |
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11 |
Issue |
558 |
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MCLab @ davi @ |
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181 |
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| Author |
Melatti, Igor; Palmer, Robert; Sawaya, Geoffrey; Yang, Yu; Kirby, Robert Mike; Gopalakrishnan, Ganesh |
| Title |
Parallel and distributed model checking in Eddy |
Type |
Journal Article |
| Year |
2009 |
Publication |
Int. J. Softw. Tools Technol. Transf. |
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11 |
Issue |
1 |
Pages |
13-25 |
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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 (1) performing overlapped asynchronous message passing, and (2) 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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Springer-Verlag |
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Berlin, Heidelberg |
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1433-2779 |
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yes |
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Sapienza @ mari @ Mpsykg09 |
Serial |
80 |
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| Author |
Melatti, Igor; Palmer, Robert; Sawaya, Geoffrey; Yang, Yu; Kirby, Robert Mike; Gopalakrishnan, Ganesh |
| Title |
Parallel and Distributed Model Checking in Eddy |
Type |
Conference Article |
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2006 |
Publication |
Model Checking Software, 13th International SPIN Workshop, Vienna, Austria, March 30 – April 1, 2006, Proceedings |
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Issue |
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Pages |
108-125 |
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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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Springer - Verlag |
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Editor |
Valmari, A. |
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Lecture Notes in Computer Science |
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3925 |
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0302-9743 |
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978-3-540-33102-5 |
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yes |
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Sapienza @ mari @ Mpsykg06 |
Serial |
81 |
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Melatti, I.; Mari, F.; Mancini, T.; Prodanovic, M.; Tronci, E. |
| Title |
A Two-Layer Near-Optimal Strategy for Substation Constraint Management via Home Batteries |
Type |
Journal Article |
| Year |
2021 |
Publication |
IEEE Transactions on Industrial Electronics |
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Issue |
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Pages |
1-1 |
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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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To appear |
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no |
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MCLab @ davi @ ref9513535 |
Serial |
190 |
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| Author |
Mazzini, Silvia; Puri, Stefano; Mari, Federico; Melatti, Igor; Tronci, Enrico |
| Title |
Formal Verification at System Level |
Type |
Conference Article |
| Year |
2009 |
Publication |
In: DAta Systems In Aerospace (DASIA), Org. EuroSpace, Canadian Space Agency, CNES, ESA, EUMETSAT. Instanbul, Turkey, EuroSpace |
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System Level Analysis calls for a language comprehensible to experts with different background and yet precise enough to support meaningful analyses. SysML is emerging as an effective balance between such conflicting goals. In this paper we outline some the results obtained as for SysML based system level functional formal verification by an ESA/ESTEC study, with a collaboration among INTECS and La Sapienza University of Roma. The study focuses on SysML based system level functional requirements techniques. |
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yes |
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Sapienza @ mari @ Dasia09 |
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20 |
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