A Semantic Framework Supporting Multilayer Networks Analysis for Rare Diseases

Understanding the role played by genetic variations in diseases, exploring genomic variants, and discovering disease-associated loci are among the most pressing challenges of genomic medicine. A huge and ever-increasing amount of information is available to researchers to address these challenges. Unfortunately, it is stored in fragmented ontologies and databases, which use heterogeneous formats and poorly integrated schemas. To overcome these limitations, the authors propose a linked data approach, based on the formalism of multilayer networks, able to integrate and harmonize biomedical information from multiple sources into a single dense network covering different aspects on Neuroendocrine Neoplasms (NENs). The proposed integration schema consists of three interconnected layers representing, respectively, information on the disease, on the affected genes, on the related biological processes and molecular functions. An easy-to-use client-server application was also developed to browse and search for information on the model supporting multilayer network analysis

A 2-D FEM thermal model to simulate water flow in a porous media: Campi Flegrei caldera case study

Abstract. Volcanic and geothermal aspects both exist in many geologically young areas. In these areas the heat transfer process is of fundamental importance, so that the thermal and fluid-dynamic processes characterizing a viscous fluid in a porous medium are very important to understand the complex dynamics of the these areas. The Campi Flegrei caldera, located west of the city of Naples, within the central-southern sector of the large graben of Campanian plain, is a region where both volcanic and geothermal phenomena are present. The upper part of the geothermal system can be considered roughly as a succession of volcanic porous material (tuff) saturated by a mixture formed mainly by water and carbon dioxide. We have implemented a finite elements approach in transient conditions to simulate water flow in a 2-D porous medium to model the changes of temperature in the geothermal system due to magmatic fluid inflow, accounting for a transient phase, not considered in the analytical solutions and fluid compressibility. The thermal model is described by means of conductive/convective equations, in which we propose a thermal source represented by a parabolic shape function to better simulate an increase of temperature in the central part (magma chamber) of a box, simulating the Campi Flegrei caldera and using more recent evaluations, from literature, for the medium's parameters (specific heat capacity, density, thermal conductivity, permeability). A best-fit velocity for the permeant is evaluated by comparing the simulated temperatures with those measured in wells drilled by Agip (Italian Oil Agency) in the 1980s in the framework of geothermal exploration. A few tens of days are enough to reach the thermal steady state, showing the quick response of the system to heat injection. The increase in the pressure due to the heat transport is then used to compute ground deformation, in particular the vertical displacements characteristics of the Campi Flegrei caldera behaviour. The vertical displacements range from 1 cm to 10 cm in accordance with the mini uplift, characterizing the recent behaviour of the caldera. The time needed to move fluid particles from the bottom to the upper layer (years) is compatible with the timing of the mini uplift

A Linked Data Application for Harmonizing Heterogeneous Biomedical Information

In the biomedical field, there is an ever-increasing number of large, fragmented, and isolated data sources stored in databases and ontologies that use heterogeneous formats and poorly integrated schemes. Researchers and healthcare professionals find it extremely difficult to master this huge amount of data and extract relevant information. In this work, we propose a linked data approach, based on multilayer networks and semantic Web standards, capable of integrating and harmonizing several biomedical datasets with different schemas and semi-structured data through a multi-model database providing polyglot persistence. The domain chosen concerns the analysis and aggregation of available data on neuroendocrine neoplasms (NENs), a relatively rare type of neoplasm. Integrated information includes twelve public datasets available in heterogeneous schemas and formats including RDF, CSV, TSV, SQL, OWL, and OBO. The proposed integrated model consists of six interconnected layers representing, respectively, information on the disease, the related phenotypic alterations, the affected genes, the related biological processes, molecular functions, the involved human tissues, and drugs and compounds that show documented interactions with them. The defined scheme extends an existing three-layer model covering a subset of the mentioned aspects. A client–server application was also developed to browse and search for information on the integrated model. The main challenges of this work concern the complexity of the biomedical domain, the syntactic and semantic heterogeneity of the datasets, and the organization of the integrated model. Unlike related works, multilayer networks have been adopted to organize the model in a manageable and stratified structure, without the need to change the original datasets but by transforming their data “on the fly” to respond to user requests

Hyperelliptic continued fractions and generalized jacobians: Minicourse given by Umberto Zannier

These are notes from the minicourse given by Umberto Zannier (Scuola Normale Superiore di Pisa). The notes were worked out by Laura Capuano, Peter Jossen,1 Christina Karolus, and Francesco Veneziano. Most of the material of these lectures, except for the numerical examples which were added by us, is already available in [45], The authors wish to thank Umberto Zannier for the lively discussions in Alpbach, and Olaf Merkert for providing computations of the examples 3.17, 3.28, 3.29, 3.33, and 3.25

Therapeutic advances in ADPKD: the future awaits

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder included in ciliopathies, representing the fourth cause of end stage renal disease (ESRD), with an estimated prevalence between 1:1000 and 1:2500. It is mainly caused by mutations in the PKD1 and PKD2 genes encoding for polycystin 1 (PC1) and polycystin 2 (PC2), which regulate differentiation, proliferation, survival, apoptosis, and autophagy. The advances in the knowledge of multiple molecular pathways involved in the pathophysiology of ADPKD led to the development of several treatments which are currently under investigation. Recently, the widespread approval of tolvaptan and, in Italy, of long-acting release octreotide (octreotide-LAR), represents but the beginning of the new therapeutic management of ADPKD patients. Encouraging results are expected from ongoing randomized controlled trials (RCTs), which are investigating not only drugs acting on the calcium/cyclic adenosin monoposphate (cAMP) pathway, the most studied target so far, but also molecules targeting specific pathophysiological pathways (e.g. epidermal growth factor (EGF) receptor, AMP-activated protein kinase (AMPK) and KEAP1-Nrf2) and sphingolipids. Moreover, studies on animal models and cultured cells have also provided further promising therapeutic strategies based on the role of intracellular calcium, cell cycle regulation, MAPK pathway, epigenetic DNA, interstitial inflammation, and cell therapy. Thus, in a near future, tailored therapy could be the key to changing the natural history of ADPKD thanks to the vigorous efforts that are being made to implement clinical and preclinical studies in this field. Our review aimed to summarize the spectrum of drugs that are available in the clinical practice and the most promising molecules undergoing clinical, animal, and cultured cell studies. Graphical abstract: [Figure not available: see fulltext.

A rock physics and seismic tomography study to characterize the structure of the Campi Flegrei caldera

The Campi Flegrei (CF) caldera experiences dramatic ground deformations unsurpassed anywhere in the world. The source responsible for this phenomenon is still debated. With the aim of exploring the structure of the caldera as well as the role of hydrothermal fluids on velocity changes, a multidisciplinary approach dealing with 3-D delay-time tomography and rock physics characterization has been followed. Selected seismic data were modeled by using a tomographic method based on an accurate finite-difference travel-time computation which simultaneously inverts P-wave and S-wave first-arrival times for both velocity model parameters and hypocenter locations. The retrieved P-wave and S-wave velocity images as well as the deduced Vp/Vs images were interpreted by using experimental measurements of rock physical properties on CF samples, to take into account steam/water phase transition mechanisms affecting P-wave and S-wave velocities. Also, modelling of petrophysical properties for site-relevant rocks constrains the role of overpressured fluids on velocity. A flat and low Vp/Vs anomaly lies at 4 km depth under the city of Pozzuoli. Earthquakes are located at the top of this anomaly. This anomaly implies the presence of fractured over-pressured gas-bearing formations and excludes the presence of melted rocks. At shallow depth, a high Vp/Vs anomaly located at 1 km suggests the presence of rocks containing fluids in the liquid phase. Finally, maps of the Vp*Vs product show a high Vp*Vs horse-shoe shaped anomaly located at 2 km depth. It is consistent with gravity data and well data and might constitute the on-land remainder of the caldera rim, detected below sea level by tomography using active source seismic data. For a more exhaustive description of the utilized methodologies, of synthetic tests for spatial resolution and uncertainty assessment and, the interpretation of results, the reader may refer to the paper Vanorio et al. (2005)

An Integrated Approach to Risk and Impacts of Geo-Resources Exploration and Exploitation

Geo-resources are widely exploited in our society, with huge benefits for both economy and communities. Nevertheless, with benefits come risks and impacts. Understanding how such risks and impacts are intrinsically borne in a given project is of critical importance for both industry and society. In particular, it is crucial to distinguish between the specific impacts related to exploiting a given energy resource and those shared with the exploitation of other energy resources. A variety of different approaches can be used to identify and assess such risks and impacts. In particular, Life Cycle Assessment (LCA) and risk assessments (RAs) are the most commonly adopted. Although both are widely used to support decision making in environmental management, they are rarely used in combination perhaps because they have been developed by largely different groups of specialists. By analyzing the structure and the ratio of the two tools, we have developed an approach for combining and harmonizing LCA and MRA; the resulting protocol envisages building MRA upon LCA both qualitatively and quantitatively. We demonstrate the approach in a case study using a virtual site (based on a real one) for geothermal energy production

Topography and structural heterogeneities in surface ground deformation: a simulation test for Somma-Vesuvius volcano

Abstract. We simulate the deformation of Somma-Vesuvius volcano due to some overpressure sources by means of a finite element 3D code. The main goal of these simulations is to investigate the influence of topography and structural heterogeneity on ground deformation. In our model the sources of deformation are embedded in an elastic linear isotropic medium and located at various depths. Geometry (shape and lateral extension) of the sources is mainly constrained by the results coming from recent seismic tomography studies. The structural heterogeneity has been modelled in terms of dynamic elastic parameters (Young's modulus) retrieved from previous seismic tomography and gravity studies. A high-resolution digital terrain model is used for the topography of the volcano subaerial edifice. Evidences from our results suggest that real topography and structural heterogeneities are key factors governing the ground deformation, which often turns being one of the most relevant problems in volcano monitoring. A large deviation from the axially symmetrical model of the displacement field is the main result of our modelling. Such an asymmetry is routinely unaccounted for when Mogi's simplistic modelling in a homogeneous medium with simplified topography is used. Our study clearly demonstrate that a better knowledge of deformation patterns can significantly help in the location of monitoring sensors as well as in the design of an efficient geodetic network