Spatial extension of stochastic Pi calculus

We introduce a spatial extension of stochastic pi-calculus that provides a formalism to model systems of discrete, connected locations. We define the extended stochastic semantics and also give deterministic semantics in terms of a system of ordinary differential equations. We describe two simple examples, one based on a standard epidemic model and one modelling resistance in plant tissues

Simulation of the cytoskeletal response of cells on grooved or patterned substrates.

We analyse the response of osteoblasts on grooved substrates via a model that accounts for the cooperative feedback between intracellular signalling, focal adhesion development and stress fibre contractility. The grooved substrate is modelled as a pattern of alternating strips on which the cell can adhere and strips on which adhesion is inhibited. The coupled modelling scheme is shown to capture some key experimental observations including (i) the observation that osteoblasts orient themselves randomly on substrates with groove pitches less than about 150 nm but they align themselves with the direction of the grooves on substrates with larger pitches and (ii) actin fibres bridge over the grooves on substrates with groove pitches less than about 150 nm but form a network of fibres aligned with the ridges, with nearly no fibres across the grooves, for substrates with groove pitches greater than about 300 nm. Using the model, we demonstrate that the degree of bridging of the stress fibres across the grooves, and consequently the cell orientation, is governed by the diffusion of signalling proteins activated at the focal adhesion sites on the ridges. For large groove pitches, the signalling proteins are dephosphorylated before they can reach the regions of the cell above the grooves and hence stress fibres cannot form in those parts of the cell. On the other hand, the stress fibre activation signal diffuses to a reasonably spatially homogeneous level on substrates with small groove pitches and hence stable stress fibres develop across the grooves in these cases. The model thus rationalizes the responsiveness of osteoblasts to the topography of substrates based on the complex feedback involving focal adhesion formation on the ridges, the triggering of signalling pathways by these adhesions and the activation of stress fibre networks by these signals.A.V. and V.S.D. acknowledge the Royal Society for supporting A.V. through a Newton International Fellowship.This is the accepted manuscript of a paper published in the Journal of the Royal Society Interface (Vigliotti A, McMeeking RM, Deshpande VS, J. R. Soc. Interface 2015, 12, 20141320, doi:10.1098/rsif.2014.1320). The final version is available at http://dx.doi.org/10.1098/rsif.2014.1320

Bayesian inference of the spatial distributions of material properties

The inverse problem of estimating the spatial distributions of elastic material properties from noisy strain measurements is ill-posed. However, it is still typically treated as an optimisation problem to maximise a likelihood function that measures the agreement between the measured and theoretically predicted strains. Here we propose an alternative approach employing Bayesian inference with Nested Sampling used to explore parameter space and compute Bayesian evidence. This approach not only aids in identifying the basis function set (referred to here as a model) that best describes the spatial material property distribution but also allows us to estimate the uncertainty in the predictions. Increasingly complex models with more parameters generate very high likelihood solutions and thus are favoured by a maximum likelihood approach. However, these models give poor predictions of the material property distributions with a large associated uncertainty as they overfit the noisy data. On the other hand, the Bayes’ factor peaks for a relatively simple model and indicates that this model is most appropriate even though its likelihood is comparatively low. Intriguingly, even for the appropriate model that has a unique maximum likelihood solution, the measurement noise is amplified to give large errors in the predictions of the maximum likelihood solution. By contrast, the mean of the posterior probability distribution reduces the effect of noise in the data and predicts the material properties with significantly higher fidelity. Simpler model selection criteria such as the Bayesian information criterion are shown to fail due to the non-Gaussian nature of the posterior distribution of the parameters. This makes accurate evaluation of the posterior distribution and the associated Bayesian evidence integral (by Nested Sampling or other means) imperative for this class of problems. The output of the Nested Sampling algorithm is also used to construct likelihood landscapes. These landscapes show the existence of multiple likelihood maxima when there is paucity of data and/or for overly complex models. They thus graphically illustrate the pitfalls in using optimisation methods to search for maximum likelihood solutions in such inverse problems.Royal Societ

The hidden world of artificial cavities in the northern Campania Plain: architectural variability and cataloging challenge

In Campania (southern Italy), sinkholes phenomena induced by the widespread presence of anthropogenic cavities in the Neapolitan and Caserta provinces are frequent and well-known. Nevertheless in many urban centers of this area, cavities have been reported in specific geological investigations although their real extent is almost unknown. In these towns the underground mining activities were performed to extract volcanic tuffs for buildings. The urban development have sealed every signal of the presence of cavities, which thus represent a geological hazard and contribute to subsoil instability of many places. The need to carry out a survey of underground quarrings in urban centers has two reasons: a) The anthropic hypogea represent an absolute documentary value, still unduly neglected and little used for the purposes of a correct and sustainable management of the territory, natural resources and historical and artistic heritage. The enhancement and sustainable reuse of hypogea contributes to enhancing the cultural and tourist promotion of a territory. b) In a correct urban management, the knowledge of the city subsoil is a priority, as the presence of cavities may easily trigger the collapse of the shallow or deeper soils. The difficulty of drawing up a univocal cataloging system lies in the definition of database framework that includes all the possible architectural, geological and geotechnical elements of the cavities. In fact, the type of extraction is not the same throughout the territory even over short distances as it was strongly conditioned by the lithological characteristics of the volcanoclastic material in the subsoil, as well as by the purpose of extraction. The construction of a cavity system initially involved an excavation carried out as a “bottle” or a “bell” from the ground level up to the tuff unit, developing at depth according to its thickness. During excavation, access points were realized through the poorly lithified or loose deposits, with a square or pseudo-circular cross-section; sometimes they were supported by containment walls made of tuff bricks resting on the lower tuff bank. A single vertical excavation is sometimes added at certain distance, so as to determine in depth the coalescence of several chambers, also through the construction of narrow tunnels or wide passages, long connecting tunnels, multiple level chambers. Access shafts were often realized with a system of stairs with one or more ramps, with steps directly carved into the tuff. This contribution will show the main cavity typologies recognized across an area north of Naples, although the study is still far from exhaustive. Data were managed into a GIS environment such as to provide a first proposal of a geological underground database framework

The homeostatic ensemble for cells

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Free-energy-based framework for early forecasting of stem cell differentiation.

Commitment of stem cells to different lineages is inherently stochastic but regulated by a range of environmental bio/chemo/mechanical cues. Here, we develop an integrated stochastic modelling framework for predicting the differentiation of hMSCs in response to a range of environmental cues, including sizes of adhesive islands, stiffness of substrates and treatment with ROCK inhibitors in both growth and mixed media. The statistical framework analyses the fluctuations of cell morphologies over approximately a 24 h period after seeding the cells in the specific environment and uses the cytoskeletal free-energy distribution to forecast the lineage the hMSCs will commit to. The cytoskeletal free energy which succinctly parametrizes the biochemical state of the cell is shown to capture hMSC commitment over a range of environments while simple morphological factors such as cell shape, tractions on their own are unable to correlate with lineages hMSCs adopt

Assessing health professionals’ perception of health literacy in Rhode Island community health centers: a qualitative study

Background: Limited health literacy is linked with poor health behaviors, limited health care access, and poor health outcomes. Improving individual and population health outcomes requires understanding and addressing barriers to promoting health literacy. Methods: Using the socio-ecological model as a guiding framework, this qualitative study (Phase 1 of a larger ongoing project) explored the interpersonal and organizational levels that may impact the health literacy levels of patients seeking care at federally qualified community health centers (FQCHCs) in Rhode Island. Focus groups were conducted with FQCHC employees (n = 37) to explore their perceptions of the health literacy skills of their patients, health literacy barriers patients encounter, and possible strategies to increase health literacy. The focus groups were audio-recorded and transcribed, and transcripts were coded using a process of open, axial, and selective coding. Codes were grouped into categories, and the constant comparative approach was used to identify themes. Results: Eight unique themes centered on health literacy, sources of health information, organizational culture’s impact, challenges from limited health literacy, and suggestions to ameliorate the impact of limited health literacy. All focus group participants were versed in health literacy and viewed health literacy as impacting patients’ health status. Participants perceived that some patients at their FQCHC have limited health literacy. Participants spoke of themselves and of their FQCHC addressing health literacy through organizational- and provider-level strategies. They also identified additional strategies (e.g., training staff and providers on health literacy, providing patients with information that includes graphics) that could be adopted or expanded upon to address and promote health literacy. Conclusions: Study findings suggest that strategies may need to be implemented at the organizational-, provider-, and patient- level to advance health literacy. The intervention phase of this project will explore intervention strategies informed by study results, and could include offering health literacy training to providers and staff to increase their understanding of health literacy to include motivation to make and act on healthy decisions and strategies to address health literacy, including the use of visual aids

Advanced documentation methodologies combined with multi-analytical approach for the preservation and restoration of 18th century architectural decorative elements at Palazzo Nuzzi in Orte (Central Italy)

This contribution reports the documentation of the conservation status and the pictorial technique of a wall painting and a stucco arch at Palazzo Nuzzi in Orte, central Italy (Viterbo district), achieved using a wide combination of non-invasive and micro-invasive diagnostic techniques. Specifically, a photogrammetric approach has been used for 2D and 3D ultraviolet fluorescence (UVF) acquisitions. Moreover, the conservation status of the wall painting has been also investigated by a non-invasive active infrared thermograghy technique, i.e. Pulse Compression Thermography (PuCT), used here for the first time on a wall painting to map the surface and sub-surface cracks in the first layers. Pigments, grounds and organic binders were characterised by X-ray fluorescence spectroscopy, micro-stratigraphic analysis, Fourier transform infrared spectroscopy and gas chromatography coupled with mass spectrometry. The results of this unique combination of advanced tools corroborated the historical-artistic attribution to the school of the architect Andrea Pozzo

Crustal Contamination and Hybridization of an Embryonic Oceanic Crust during the Red Sea Rifting (Tihama Asir Igneous Complex, Saudi Arabia)

The Red Sea rift system represents a key case study of the transition from a continental to an oceanic rift. The Red Sea rifting initiated in Late Oligocene to Early Miocene (24-23 Ma) and was accompanied by extensive magmatism throughout the rifted basin, from Afar and Yemen to northern Egypt. Here, we present a petrological and geochemical study of two gabbro bodies and associated basalts from the Tihama Asir igneous complex, which formed at 24-20 Ma within the rifted Arabian-Nubian Shield (ANS). The Tihama Asir is therefore an ideal location to study the initial phase of syn-rift magmatism and its influence on the geodynamic evolution of the Red Sea rift system. The most primitive olivine gabbros present modal, bulk and mineral compositions consistent with formation from Mid-Ocean Ridge Basalt (MORB)-type parental melts, whereas the evolved olivine-free gabbros and oxide-bearing gabbros show saturation of phlogopite and a crystal line of descent diverging from fractional crystallization trends. In detail, whole-rock and mineral compositions in the most evolved lithologies show high Light over Middle Rare Earth Elements (LREE/MREE) ratios (La-N/Sm-N = 0.89-1.31) and selective enrichments in Sr, K and highly incompatible elements (Rb, Ba, U, Th). We relate these geochemical characteristics to a process of progressive assimilation of host continental crust during the emplacement of the gabbroic plutons. Interestingly, high LREE/MREE ratios (La-N/Sm-N = 1.45-4.58) and high Rb, Ba, Th and U contents also characterize the basaltic dike swarms associated to the gabbros. Incompatible trace element compositions of these basalts approach those of the melts that formed the most hybridized gabbros. Therefore, we propose that the dike swarms represent melts partially contaminated by assimilation of continental crust material, extracted from the underlying gabbroic crystal mush. Our results suggest that early syn-rift magmatism led to the partial replacement of the thinned continental crust by MORB-type gabbroic bodies, in turn suggesting that oceanic magmatism started prior to continental break-up. Extensive syn-rift magmatism is consistent with the interpretation of the southern Red Sea rift system as a volcanic rifted margin. One possible implication of this study is that extensive but diffuse syn-rift magmatism possibly hampered continental break-up, leading to a protracted rifting stage