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Giuseppe Della Penna, Benedetto Intrigila, Enrico Tronci, and Marisa Venturini Zilli. "Synchronized Regular Expressions." Electr. Notes Theor. Comput. Sci. 62 (2002): 195–210. Notes: TOSCA 2001, Theory of Concurrency, Higher Order Languages and Types.
Abstract: Text manipulation is one of the most common tasks for everyone using a computer. The increasing number of textual information in electronic format that every computer user collects everyday stresses the need of more powerful tools to interact with texts. Indeed, much work has been done to provide nonprogramming tools that can be useful for the most common text manipulation issues. Regular Expressions (RE), introduced by Kleene, are well–known in the formal language theory. RE received several extensions, depending on the application of interest. In almost all the implementations of RE search algorithms (e.g. the egrep [A] UNIX command, or the Perl [17] language pattern matching constructs) we find backreferences (as defind in [1]), i.e. expressions that make reference to the string matched by a previous subexpression. Generally speaking, it seems that all the kinds of synchronizations between subexpressions in a RE can be very useful when interacting with texts. Therefore, we introduce the Synchronized Regular Expressions (SRE) as a derivation of the Regular Expressions. We use SRE to present a formal study of the already known backreferences extension, and of a new extension proposed by us, which we call the synchronized exponents. Moreover, since we are talking about formalisms that should have a practical utility and can be used in the real world, we have the problem of how to present SRE to the final users. Therefore, in this paper we also propose a user–friendly syntax for SRE to be used in implementations of SRE–powered search algorithms.
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T. Mancini, F. Mari, A. Massini, I. Melatti, and E. Tronci. "On Checking Equivalence of Simulation Scripts." Journal of Logical and Algebraic Methods in Programming (2021): 100640. ISSN: 2352-2208. DOI: 10.1016/j.jlamp.2021.100640.
Abstract: To support Model Based Design of Cyber-Physical Systems (CPSs) many simulation based approaches to System Level Formal Verification (SLFV) have been devised. Basically, these are Bounded Model Checking approaches (since simulation horizon is of course bounded) relying on simulators to compute the system dynamics and thereby verify the given system properties. The main obstacle to simulation based SLFV is the large number of simulation scenarios to be considered and thus the huge amount of simulation time needed to complete the verification task. To save on computation time, simulation based SLFV approaches exploit the capability of simulators to save and restore simulation states. Essentially, such a time saving is obtained by optimising the simulation script defining the simulation activity needed to carry out the verification task. Although such approaches aim to (bounded) formal verification, as a matter of fact, the proof of correctness of the methods to optimise simulation scripts basically relies on an intuitive semantics for simulation scripting languages. This hampers the possibility of formally showing that the optimisations introduced to speed up the simulation activity do not actually omit checking of relevant behaviours for the system under verification. The aim of this paper is to fill the above gap by presenting an operational semantics for simulation scripting languages and by proving soundness and completeness properties for it. This, in turn, enables formal proofs of equivalence between unoptimised and optimised simulation scripts.
Keywords: Formal verification, Simulation based formal verification, Formal Verification of cyber-physical systems, System-level formal verification
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Federico Mari, Igor Melatti, Ivano Salvo, and Enrico Tronci. "From Boolean Relations to Control Software." In Proceedings of ICSEA 2011, The Sixth International Conference on Software Engineering Advances, 528–533. ThinkMind, 2011. ISSN: 978-1-61208-165-6. Notes: Best Paper Award.
Abstract: Many software as well digital hardware automatic synthesis methods define the set of implementations meeting the given system specifications with a boolean relation K. In such a context a fundamental step in the software (hardware) synthesis process is finding effective solutions to the functional equation defined by K. This entails finding a (set of) boolean function(s) F (typically represented using OBDDs, Ordered Binary Decision Diagrams) such that: 1) for all x for which K is satisfiable, K(x, F(x)) = 1 holds; 2) the implementation of F is efficient with respect to given implementation parameters such as code size or execution time. While this problem has been widely studied in digital hardware synthesis, little has been done in a software synthesis context. Unfortunately the approaches developed for hardware synthesis cannot be directly used in a software context. This motivates investigation of effective methods to solve the above problem when F has to be implemented with software. In this paper we present an algorithm that, from an OBDD representation for K, generates a C code implementation for F that has the same size as the OBDD for F and a WCET (Worst Case Execution Time) linear in nr, being n = |x| the number of input arguments for functions in F and r the number of functions in F.
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Federico Mari, Igor Melatti, Ivano Salvo, and Enrico Tronci. "Synthesizing Control Software from Boolean Relations." International Journal on Advances in Software vol. 5, nr 3&4 (2012): 212–223. IARIA. ISSN: 1942-2628.
Abstract: Many software as well digital hardware automatic
synthesis methods define the set of
implementations meeting the given system
specifications with a boolean relation K. In
such a context a fundamental step in the software
(hardware) synthesis process is finding effective
solutions to the functional equation defined by
K. This entails finding a (set of) boolean
function(s) F (typically represented using
OBDDs, Ordered Binary Decision Diagrams)
such that: 1) for all x for which K is
satisfiable, K(x, F(x)) = 1 holds; 2) the
implementation of F is efficient with respect
to given implementation parameters such as code
size or execution time. While this problem has
been widely studied in digital hardware synthesis,
little has been done in a software synthesis
context. Unfortunately, the approaches developed
for hardware synthesis cannot be directly used in
a software context. This motivates investigation
of effective methods to solve the above problem
when F has to be implemented with software. In
this paper, we present an algorithm that, from an
OBDD representation for K, generates a C code
implementation for F that has the same size as
the OBDD for F and a worst case execution time
linear in nr, being n = |x| the number of
input arguments for functions in F and r the
number of functions in F. Moreover, a formal
proof of the proposed algorithm correctness is
also shown. Finally, we present experimental
results showing effectiveness of the proposed
algorithm.
Keywords: Control Software Synthesis; Embedded Systems; Model Checking
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R. Ehrig, T. Dierkes, S. Schaefer, S. Roeblitz, E. Tronci, T. Mancini, I. Salvo, V. Alimguzhin, F. Mari, I. Melatti et al. "An integrative approach for model driven computation of treatments in reproductive medicine." In Proceedings of the 15th International Symposium on Mathematical and Computational Biology (BIOMAT 2015), Rorkee, India., 2015. DOI: 10.1142/9789813141919_0005.
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T. Mancini, F. Mari, I. Melatti, I. Salvo, and E. Tronci. "An Efficient Algorithm for Network Vulnerability Analysis Under Malicious Attacks." In Foundations of Intelligent Systems – 24th International Symposium, ISMIS 2018, Limassol, Cyprus, October 29-31, 2018, Proceedings, 302–312., 2018. Notes: Best Paper. DOI: 10.1007/978-3-030-01851-1_29.
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S. Sinisi, V. Alimguzhin, T. Mancini, E. Tronci, and B. Leeners. "Complete populations of virtual patients for in silico clinical trials." Bioinformatics (2021): 1–8. ISSN: 1367-4803. DOI: 10.1093/bioinformatics/btaa1026.
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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F. Maggioli, T. Mancini, and E. Tronci. "SBML2Modelica: Integrating biochemical models within open-standard simulation ecosystems." Bioinformatics 36, no. 7 (2019): 2165–2172. ISSN: 1367-4803. DOI: 10.1093/bioinformatics/btz860.
Abstract: SBML is the most widespread language for the definition of biochemical models. Although dozens of SBML simulators are available, there is a general lack of support to the integration of SBML models within open-standard general-purpose simulation ecosystems. This hinders co-simulation and integration of SBML models within larger model networks, in order to, e.g., enable in-silico clinical trials of drugs, pharmacological protocols, or engineering artefacts such as biomedical devices against Virtual Physiological Human models.Modelica is one of the most popular existing open-standard general-purpose simulation languages, supported by many simulators. Modelica models are especially suited for the definition of complex networks of heterogeneous models from virtually all application domains. Models written in Modelica (and in 100+ other languages) can be readily exported into black-box Functional Mock-Up Units (FMUs), and seamlessly co-simulated and integrated into larger model networks within open-standard language-independent simulation ecosystems.In order to enable SBML model integration within heterogeneous model networks, we present SBML2Modelica, a software system translating SBML models into well-structured, user-intelligible, easily modifiable Modelica models. SBML2Modelica is SBML Level 3 Version 2 -compliant and succeeds on 96.47% of the SBML Test Suite Core (with a few rare, intricate, and easily avoidable combinations of constructs unsupported and cleanly signalled to the user). Our experimental campaign on 613 models from the BioModels database (with up to 5438 variables) shows that the major open-source (general-purpose) Modelica and FMU simulators achieve performance comparable to state-of-the-art specialised SBML simulators.SBML2Modelica is written in Java and is freely available for non-commercial use at https://bitbucket.org/mclab/sbml2modelica
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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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B. Leeners, T. H. C. Krueger, K. Geraedts, E. Tronci, T. Mancini, M. Egli, S. Roeblitz, L. Saleh, K. Spanaus, C. Schippert et al. "Associations Between Natural Physiological and Supraphysiological Estradiol Levels and Stress Perception." Frontiers in Psychology 10 (2019): 1296. ISSN: 1664-1078. DOI: 10.3389/fpsyg.2019.01296.
Abstract: Stress is a risk factor for impaired general, mental and reproductive health. The role of physiological and supraphysiological estradiol concentrations in stress perception and stress processing is less well understood. We therefore, conducted a prospective observational study to investigate the association between estradiol, stress perception and stress-related cognitive performance within serial measurements either during the natural menstrual cycle or during fertility treatment, where estradiol levels are strongly above the physiological level of a natural cycle and consequently, represent a good model to study dose-dependent effects of estradiol. Data from 44 women receiving in vitro fertilization at the Department of Reproductive Endocrinology in Zurich, Switzerland was compared to data from 88 women with measurements during their natural menstrual cycle. The german version of the Perceived Stress Questionnaire (PSQ) and the Cognitive Bias Test (CBT), in which cognitive performance is tested under time stress were used to evaluate subjective and functional aspects of stress. Estradiol levels were investigated at four different time points during the menstrual cycle and at two different time points during a fertility treatment. Cycle phase were associated with PSQ worry and cognitive bias in normally cycling women, but different phases of fertility treatment were not associated with subjectively perceived stress and stress-related cognitive bias. PSQ lack of joy and PSQ demands related to CBT in women receiving fertility treatment but not in women with a normal menstrual cycle. Only strong changes of the estradiol level during fertility treatment were weakly associated with CBT, but not with subjectively experienced stress. Our research emphasises the multidimensional character of stress and the necessity to adjust stress research to the complex nature of stress perception and processing. Infertility is associated with an increased psychological burden in patients. However, not all phases of the process to overcome infertility do significantly increase patient stress levels. Also, research on the psychological burden of infertility should consider that stress may vary during the different phases of fertility treatment.
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