Emanuela Merelli

Pietro Liò, Emanuela Merelli, Nicola Paoletti

We introduce a model checking approach to diagnose the emerging of bone pathologies. The implementation of a new model of bone remodeling in PRISM has led to an interesting characterization of osteoporosis as a defective bone remodeling dynamics with respect to other bone pathologies. Our approach allows to derive three types of model checking-based diagnostic estimators. The first diagnostic measure focuses on the level of bone mineral density, which is currently used in medical practice. In addition, we have introduced a novel diagnostic estimator which uses the full patient clinical record, here simulated using the modeling framework. This estimator detects rapid (months) negative changes in bone mineral density. Independently of the actual bone mineral density, when the decrease occurs rapidly it is important to alarm the patient and monitor him/her more closely to detect insurgence of other bone co-morbidities. A third estimator takes into account the variance of the bone density, which could address the investigation of metabolic syndromes, diabetes and cancer. Our implementation could make use of different logical combinations of these statistical estimators and could incorporate other biomarkers for other systemic co-morbidities (for example diabetes and thalassemia). We are delighted to report that the combination of stochastic modeling with formal methods motivate new diagnostic framework for complex pathologies. In particular our approach takes into consideration important properties of biosystems such as multiscale and self-adaptiveness. The multi-diagnosis could be further expanded, inching towards the complexity of human diseases. Finally, we briefly introduce self-adaptiveness in formal methods which is a key property in the regulative mechanisms of biological systems and well known in other mathematical and engineering areas.

Pietro Liò, Emanuela Merelli, Nicola Paoletti

We investigate the use of hybrid techniques in complex processes of infectious diseases. Since predictive disease models in biomedicine require a multiscale approach for understanding the molecule-cell-tissue-organ-body interactions, heterogeneous methodologies are often employed for describing the different biological scales. Hybrid models provide effective means for complex disease modelling where the action and dosage of a drug or a therapy could be meaningfully investigated: the infection dynamics can be classically described in a continuous fashion, while the scheduling of multiple treatment discretely. We define an algebraic language for specifying general disease processes and multiple treatments, from which a semantics in terms of hybrid dynamical system can be derived. Then, the application of control-theoretic tools is proposed in order to compute the optimal scheduling of multiple therapies. The potentialities of our approach are shown in the case study of the SIR epidemic model and we discuss its applicability on osteomyelitis, a bacterial infection affecting the bone remodelling system in a specific and multiscale manner. We report that formal languages are helpful in giving a general homogeneous formulation for the different scales involved in a multiscale disease process; and that the combination of hybrid modelling and control theory provides solid grounds for computational medicine.

Marco Caputo, Michele Russo, Emanuela Merelli

This work seeks to tackle the inherent complexity of dataspaces by introducing a novel data structure that can represent datasets across multiple levels of abstraction, ranging from local to global. We propose the concept of a multilevel graph, which is equipped with two fundamental operations: contraction and expansion of its topology. This multilevel graph is specifically designed to fulfil the requirements for incremental abstraction and flexibility, as outlined in existing definitions of dataspaces. Furthermore, we provide a comprehensive suite of methods for manipulating this graph structure, establishing a robust framework for data analysis. While its effectiveness has been empirically validated for unstructured data, its application to structured data is also inherently viable. Preliminary results are presented through a real-world scenario based on a collection of dream reports.

Emanuela Merelli, Anita Wasilewska

It is a great pleasure to write this tribute in honor of Scott A. Smolka on his 65th birthday. We revisit Goldin, Smolka hypothesis that persistent Turing machine (PTM) can capture the intuitive notion of sequential interaction computation. We propose a topological setting to model the abstract concept of environment. We use it to define a notion of a topological Turing machine (TTM) as a universal model for interactive computation and possible model for concurrent computation.

Matteo Rucco, David M. S. Rodrigues, Emanuela Merelli et al.

This work introduces an integrative approach based on Q-analysis with machine learning. The new approach, called Neural Hypernetwork, has been applied to a case study of pulmonary embolism diagnosis. The objective of the application of neural hyper-network to pulmonary embolism (PE) is to improve diagnose for reducing the number of CT-angiography needed. Hypernetworks, based on topological simplicial complex, generalize the concept of two-relation to many-body relation. Furthermore, Hypernetworks provide a significant generalization of network theory, enabling the integration of relational structure, logic and analytic dynamics. Another important results is that Q-analysis stays close to the data, while other approaches manipulate data, projecting them into metric spaces or applying some filtering functions to highlight the intrinsic relations. A pulmonary embolism (PE) is a blockage of the main artery of the lung or one of its branches, frequently fatal. Our study uses data on 28 diagnostic features of 1,427 people considered to be at risk of PE. The resulting neural hypernetwork correctly recognized 94% of those developing a PE. This is better than previous results that have been obtained with other methods (statistical selection of features, partial least squares regression, topological data analysis in a metric space).

Emanuela Merelli, Nicola Paoletti, Luca Tesei

A hierarchical model for multi-level adaptive systems is built on two basic levels: a lower behavioural level B accounting for the actual behaviour of the system and an upper structural level S describing the adaptation dynamics of the system. The behavioural level is modelled as a state machine and the structural level as a higher-order system whose states have associated logical formulas (constraints) over observables of the behavioural level. S is used to capture the global and stable features of B, by a defining set of allowed behaviours. The adaptation semantics is such that the upper S level imposes constraints on the lower B level, which has to adapt whenever it no longer can satisfy them. In this context, we introduce weak and strong adaptabil- ity, i.e. the ability of a system to adapt for some evolution paths or for all possible evolutions, respectively. We provide a relational characterisation for these two notions and we show that adaptability checking, i.e. deciding if a system is weak or strong adaptable, can be reduced to a CTL model checking problem. We apply the model and the theoretical results to the case study of motion control of autonomous transport vehicles.

Emanuela Merelli, Nicola Paoletti, Luca Tesei

This work introduces a general multi-level model for self-adaptive systems. A self-adaptive system is seen as composed by two levels: the lower level describing the actual behaviour of the system and the upper level accounting for the dynamically changing environmental constraints on the system. In order to keep our description as general as possible, the lower level is modelled as a state machine and the upper level as a second-order state machine whose states have associated formulas over observable variables of the lower level. Thus, each state of the second-order machine identifies the set of lower-level states satisfying the constraints. Adaptation is triggered when a second-order transition is performed; this means that the current system no longer can satisfy the current high-level constraints and, thus, it has to adapt its behaviour by reaching a state that meets the new constraints. The semantics of the multi-level system is given by a flattened transition system that can be statically checked in order to prove the correctness of the adaptation model. To this aim we formalize two concepts of weak and strong adaptability providing both a relational and a logical characterization. We report that this work gives a formal computational characterization of multi-level self-adaptive systems, evidencing the important role that (theoretical) computer science could play in the emerging science of complex systems.