Programmable models of growth and mutation of cancer-cell populations

In this paper we propose a systematic approach to construct mathematical models describing populations of cancer-cells at different stages of disease development. The methodology we propose is based on stochastic Concurrent Constraint Programming, a flexible stochastic modelling language. The methodology is tested on (and partially motivated by) the study of prostate cancer. In particular, we prove how our method is suitable to systematically reconstruct different mathematical models of prostate cancer growth - together with interactions with different kinds of hormone therapy - at different levels of refinement.Comment: In Proceedings CompMod 2011, arXiv:1109.104

Mean-Field Limits Beyond Ordinary Differential Equations

16th International School on Formal Methods for the Design of Computer, Communication, and Software Systems, SFM 2016, Bertinoro, Italy, June 20-24, 2016, Advanced LecturesInternational audienceWe study the limiting behaviour of stochastic models of populations of interacting agents, as the number of agents goes to infinity. Classical mean-field results have established that this limiting behaviour is described by an ordinary differential equation (ODE) under two conditions: (1) that the dynamics is smooth; and (2) that the population is composed of a finite number of homogeneous sub-populations, each containing a large number of agents. This paper reviews recent work showing what happens if these conditions do not hold. In these cases, it is still possible to exhibit a limiting regime at the price of replacing the ODE by a more complex dynamical system. In the case of non-smooth or uncertain dynamics, the limiting regime is given by a differential inclusion. In the case of multiple population scales, the ODE is replaced by a stochastic hybrid automaton

Characterization methodology for re-using marble slurry in industrial applications

Nowadays calcium carbonate has a great importance in different industrial fields and currently there is the opportunity of appreciate the potential value of marble waste and convert it into marketable products. Marble slurry samples, collected from different dimension stone treatment plants in Orosei marble district (Sardinia - Italy), were chemically, physically, mineralogically, and morphologically analyzed and the obtained data were evaluated for compatibility with the marketable micronized CaCO3 specifications required by some industrial sectors, estimating the prospects of recovered CaCO3 utilization. Besides the economic benefits, transforming a waste into an important economic resource involves environmental advantages, due to reduced marble waste landfills, and sustainability promotion

Among once-daily regimens, single tablet regimens (STRs) are associated with better adherence

Previous published evidences showed that taking HAART once-daily (OD) is associated to better adherence when compared to BID or TID regimens. However, no further studies investigated whether, among OD regimens, adherence levels can be differently influenced. Aim of the study was to evaluate levels of self-reported adherence in HIV+ people according to type of HAART dosing (STR, OD with more than one pill or BID). To limit reporting biases, the study was performed in five different non-clinic settings covering North and Central Italy. A total of 230 patients on stable HAART were asked to complete a semi-structured, anonymous questionnaire reporting their attitude toward HAART, their adherence and the acceptability of their regimen. Self-perception of adherence was also investigated with a single item for comparison with real adherence behavior. Most of the subjects were males (66%) with a mean age of 46 years, with higher education level (72%) and a long history of HIV infection (mean 13.6 years). 17% of patients were on a first-line regimen. 21% reported to miss at least one dose during the past week (STR: 6%; OD >1 pill 23% and BID 21%; p<0.05). People taking STR and BID tend to report less discontinuations (all the drug of the day for at least 3 times in a month) compared to OD>1 pill (6 and 4% vs 11%). People taking therapies other than HAART reported similar adherence levels of people taking only HAART, even when stratified for dosing groups. Even people judging their adherence as ‘optimal’ or ‘very good’, 10 and 17% respectively, reported having missed a dose during the last week. At stepwise regression model, optimal adherence was correlated to being male (OR: 2.38; 95% CI: 1.19–4.74), younger (OR: 3.04; 95% CI: 1.01–9.13) and with a shorter HIV infection (OR: 3.58; 95% CI: 1.04–12.38). People taking simpler once-daily STR tend to report better adherence than people taking OD>1 pill or BID. Perception of optimal adherence is largely variable among HIV-infected people taking HAART, although only a minority of subjects showing less than perfect adherence do judge their behavior as ‘optimal’

Kinematic/Dynamic Characteristics for Visual and Kinesthetic Virtual Environments

Work was carried out on two topics of principal importance to current progress in virtual environment research at NASA Ames and elsewhere. The first topic was directed at maximizing the temporal dynamic response of visually presented Virtual Environments (VEs) through reorganization and optimization of system hardware and software. The final results of this portion of the work was a VE system in the Advanced Display and Spatial Perception Laboratory at NASA Ames capable of updating at 60 Hz (the maximum hardware refresh rate) with latencies approaching 30 msec. In the course of achieving this system performance, specialized hardware and software tools for measurement of VE latency and analytic models correlating update rate and latency for different system configurations were developed. The second area of activity was the preliminary development and analysis of a novel kinematic architecture for three Degree Of Freedom (DOF) haptic interfaces--devices that provide force feedback for manipulative interaction with virtual and remote environments. An invention disclosure was filed on this work and a patent application is being pursued by NASA Ames. Activities in these two areas are expanded upon below

Process algebra modelling styles for biomolecular processes

We investigate how biomolecular processes are modelled in process algebras, focussing on chemical reactions. We consider various modelling styles and how design decisions made in the definition of the process algebra have an impact on how a modelling style can be applied. Our goal is to highlight the often implicit choices that modellers make in choosing a formalism, and illustrate, through the use of examples, how this can affect expressability as well as the type and complexity of the analysis that can be performed

Probabilistic Model Checking for Continuous-Time Markov Chains via Sequential Bayesian Inference

Probabilistic model checking for systems with large or unbounded state space is a challenging computational problem in formal modelling and its applications. Numerical algorithms require an explicit representation of the state space, while statistical approaches require a large number of samples to estimate the desired properties with high confidence. Here, we show how model checking of time-bounded path properties can be recast exactly as a Bayesian inference problem. In this novel formulation the problem can be efficiently approximated using techniques from machine learning. Our approach is inspired by a recent result in statistical physics which derived closed form differential equations for the first-passage time distribution of stochastic processes. We show on a number of non-trivial case studies that our method achieves both high accuracy and significant computational gains compared to statistical model checking