B. Leeners, T. Krueger, K. Geraedts, E. Tronci, T. Mancini, F. Ille, M. Egli, S. Roeblitz, D. Wunder, L. Saleh et al. "Cognitive function in association with high estradiol levels resulting from fertility treatment." Hormones and Behavior 130 (2021): 104951. ISSN: 0018-506x. DOI: 10.1016/j.yhbeh.2021.104951.
Abstract: The putative association between hormones and cognitive performance is controversial. While there is evidence that estradiol plays a neuroprotective role, hormone treatment has not been shown to improve cognitive performance. Current research is flawed by the evaluation of combined hormonal effects throughout the menstrual cycle or in the menopausal transition. The stimulation phase of a fertility treatment offers a unique model to study the effect of estradiol on cognitive function. This quasi-experimental observational study is based on data from 44 women receiving IVF in Zurich, Switzerland. We assessed visuospatial working memory, attention, cognitive bias, and hormone levels at the beginning and at the end of the stimulation phase of ovarian superstimulation as part of a fertility treatment. In addition to inter-individual differences, we examined intra-individual change over time (within-subject effects). The substantial increases in estradiol levels resulting from fertility treatment did not relate to any considerable change in cognitive functioning. As the tests applied represent a broad variety of cognitive functions on different levels of complexity and with various brain regions involved, we can conclude that estradiol does not show a significant short-term effect on cognitive function.
Keywords: Cognition, Estrogen, Estradiol, Fertility treatment, Attention, Cognitive bias
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S. Sinisi, V. Alimguzhin, T. Mancini, and E. Tronci. "Reconciling interoperability with efficient Verification and Validation within open source simulation environments." Simulation Modelling Practice and Theory (2021): 102277. ISSN: 1569-190x. DOI: 10.1016/j.simpat.2021.102277.
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.
Keywords: Simulation, Verification and Validation, Interoperability, FMI/FMU, Model Exchange, Cyber-Physical Systems
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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. A Map-Reduce Parallel Approach to Automatic Synthesis of Control Software. Vol. abs/1210.2276. CoRR, Technical Report, 2012.
Abstract: Many Control Systems are indeed Software Based Control Systems, i.e. control systems whose controller consists of control software running on a microcontroller device. This motivates investigation on Formal Model Based Design approaches for automatic synthesis of control software.
Available algorithms and tools (e.g., QKS) may require weeks or even months of computation to synthesize control software for large-size systems. This motivates search for parallel algorithms for control software synthesis.
In this paper, we present a map-reduce style parallel algorithm for control software synthesis when the controlled system (plant) is modeled as discrete time linear hybrid system. Furthermore we present an MPI-based implementation PQKS of our algorithm. To the best of our knowledge, this is the first parallel approach for control software synthesis.
We experimentally show effectiveness of PQKS on two classical control synthesis problems: the inverted pendulum and the multi-input buck DC/DC converter. Experiments show that PQKS efficiency is above 65%. As an example, PQKS requires about 16 hours to complete the synthesis of control software for the pendulum on a cluster with 60 processors, instead of the 25 days needed by the sequential algorithm in QKS.
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Vadim Alimguzhin, Federico Mari, Igor Melatti, Ivano Salvo, and Enrico Tronci. On Model Based Synthesis of Embedded Control Software. Vol. abs/1207.4474. CoRR, Technical Report, 2012.
Abstract: Many Embedded Systems are indeed Software Based Control Systems (SBCSs), that is control systems whose controller consists of control software running on a microcontroller device. This motivates investigation on Formal Model Based Design approaches for control software. Given the formal model of a plant as a Discrete Time Linear Hybrid System and the implementation specifications (that is, number of bits in the Analog-to-Digital (AD) conversion) correct-by-construction control software can be automatically generated from System Level Formal Specifications of the closed loop system (that is, safety and liveness requirements), by computing a suitable finite abstraction of the plant.
With respect to given implementation specifications, the automatically generated code implements a time optimal control strategy (in terms of set-up time), has a Worst Case Execution Time linear in the number of AD bits $b$, but unfortunately, its size grows exponentially with respect to $b$. In many embedded systems, there are severe restrictions on the computational resources (such as memory or computational power) available to microcontroller devices.
This paper addresses model based synthesis of control software by trading system level non-functional requirements (such us optimal set-up time, ripple) with software non-functional requirements (its footprint). Our experimental results show the effectiveness of our approach: for the inverted pendulum benchmark, by using a quantization schema with 12 bits, the size of the small controller is less than 6% of the size of the time optimal one.
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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. Vol. abs/1207.4098. CoRR, Technical Report, 2012.
Abstract: Many Embedded Systems are indeed Software Based Control Systems, that is control systems whose controller consists of control software running on a microcontroller device. This motivates investigation on Formal Model Based Design approaches for automatic synthesis of embedded systems control software. This paper addresses control software synthesis for discrete time nonlinear systems. We present a methodology to overapproximate the dynamics of a discrete time nonlinear hybrid system H by means of a discrete time linear hybrid system L(H), in such a way that controllers for L(H) are guaranteed to be controllers for H. We present experimental results on the inverted pendulum, a challenging and meaningful benchmark in nonlinear Hybrid Systems control.
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