BACKGROUND: issues and limitations related to accessibility, understandability and ease of use of signalling pathway databases may hamper or divert research workflow, leading, in the worst case, to the generation of confusing reference frameworks and misinterpretation of experimental results. In an attempt to retrieve signalling pathway data related to a specific set of test genes, we queried and analysed the results from six of the major curated signalling pathway databases: Reactome, PathwayCommons, KEGG, InnateDB, PID, and Wikipathways. FINDINGS: although we expected differences - often a desirable feature for the integration of each individual query, we observed variations of exceptional magnitude, with disproportionate quality and quantity of the results. Some of the more remarkable differences can be explained by the diverse conceptual designs and purposes of the databases, the types of data stored and the structure of the query, as well as by missing or erroneous descriptions of the search procedure. To go beyond the mere enumeration of these problems, we identified a number of operational features, in particular inner and cross coherence, which, once quantified, offer objective criteria to choose the best source of information. CONCLUSIONS: in silico biology heavily relies on the information stored in databases. To ensure that computational biology mirrors biological reality and offers focused hypotheses to be experimentally validated, coherence of data codification is crucial and yet highly underestimated. We make practical recommendations for the end-user to cope with the current state of the databases as well as for the maintainers of those databases to contribute to the goal of the full enactment of the open data paradigm.

Genetic association studies of age-related, chronic human diseases often suffer from a lack of power to detect modest effects. Here we propose an alternative approach of including healthy centenarians as a more homogeneous and extreme control group. As a proof of principle we focused on type 2 diabetes (T2D) and assessed /genotypic associations of 31 SNPs associated with T2D, diabetes complications and metabolic diseases and SNPs of genes relevant for telomere stability and age-related diseases. We hypothesized that the frequencies of risk variants are inversely correlated with decreasing health and longevity. We performed association analyses comparing diabetic patients and non-diabetic controls followed by association analyses with extreme phenotypic groups (T2D patients with complications and centenarians). Results drew attention to rs7903146 (TCF7L2 gene) that showed a constant increase in the frequencies of risk genotype (TT) from centenarians to diabetic patients who developed macro-complications and the strongest genotypic association was detected when diabetic patients were compared to centenarians (p_value = 9.066*10(-)(7)). We conclude that robust and biologically relevant associations can be obtained when extreme phenotypes, even with a small sample size, are compared.

BACKGROUND: Type 2 diabetes mellitus (T2D) is a common age-related disease, and is a major health concern, particularly in developed countries where the population is aging, including Europe. The multi-scale immune system simulator for the onset of type 2 diabetes (MISSION-T2D) is a European Union-funded project that aims to develop and validate an integrated, multilevel, and patient-specific model, incorporating genetic, metabolic, and nutritional data for the simulation and prediction of metabolic and inflammatory processes in the onset and progression of T2D. The project will ultimately provide a tool for diagnosis and clinical decision making that can estimate the risk of developing T2D and predict its progression in response to possible therapies. Recent data showed that T2D and its complications, specifically in the heart, kidney, retina, and feet, should be considered a systemic disease that is sustained by a pervasive, metabolically-driven state of inflammation. Accordingly, there is an urgent need (1) to understand the complex mechanisms underpinning the onset of this disease, and (2) to identify early patient-specific diagnostic parameters and related inflammatory indicators. OBJECTIVE: We aim to accomplish this mission by setting up a multi-scale model to study the systemic interactions of the biological mechanisms involved in response to a variety of nutritional and metabolic stimuli and stressors. METHODS: Specifically, we will be studying the biological mechanisms of immunological/inflammatory processes, energy intake/expenditure ratio, and cell cycle rate. The overall architecture of the model will exploit an already established immune system simulator as well as several discrete and continuous mathematical methods for modeling of the processes critically involved in the onset and progression of T2D. We aim to validate the predictions of our models using actual biological and clinical data. RESULTS: This study was initiated in March 2013 and is expected to be completed by February 2016. CONCLUSIONS: MISSION-T2D aims to pave the way for translating validated multilevel immune-metabolic models into the clinical setting of T2D. This approach will eventually generate predictive biomarkers for this disease from the integration of clinical data with metabolic, nutritional, immune/inflammatory, genetic, and gut microbiota profiles. Eventually, it should prove possible to translate these into cost-effective and mobile-based diagnostic tools.

Tombe aristocratiche dall'acropoli di Monte Sannace. Indagini sulle strutture, sui contesti e sulle decorazioni dipinte

Non-linear stability of vertical throughflows in porous layers, uniformly heated and salted from below, is analyzed. The definitively boundedness of the solutions (existence of absorbing sets in the phase space) is proved. Conditions guaranteeing global non-linear asymptotic stability have been found. In closed form, the critical Rayleigh number has been found.

The Cournot duopoly game modeled by Kopel, with adaptive expectations, is generalized by introducing the self-diffusion and cross-diffusion terms. General properties, such as boundedness and uniqueness, are obtained. Nonlinear stability results are reached by the analysis of the stability of a ODE system.

In this article a nonnegative blind source separation technique, known as nonnegative matrix factorization, is applied to microdiffraction data in order to extract characteristic patterns and to determine their spatial distribution in tissue typing problems occurring in bone-tissue engineering. In contrast to other blind source separation methods, nonnegative matrix factorization only requires nonnegative constraints on the extracted sources and corresponding weights, which makes it suitable for the analysis of data occurring in a variety of applications. In particular, here nonnegative matrix factorization is hierarchically applied to two-dimensional meshes of X-ray diffraction data measured in bone samples with implanted tissue. Such data are characterized by nonnegative profiles and their analysis provides significant information about the structure of possibly new deposited bone tissue. A simulation and real data studies show that the proposed method is able to retrieve the patterns of interest and to provide a reliable and accurate segmentation of the given X-ray diffraction data.

The aim of this work is to analyze the hydroacoustic behavior of a marine propeller through the acoustic analogy and to test the versatility and effectiveness of this approach in dealing with the many (and relatively unexplored) issues concerning the underwater noise and its numerical prediction. In particular, a propeller in a noncavitating open water condition is examined here by coupling a Reynolds averaged Navier-Stokes hydrodynamic solver to a hydroacoustic code implementing different resolution forms of the Ffowcs Williams-Hawkings (FWH) equation. The numerical results suggest that unlike the analogous aeronautical problem, where the role played by the nonlinear quadrupole sources is known to be relevant just at high transonic or supersonic regime, the pressure field underwater seems to be significantly affected by the flow nonlinearities, while the contribution from the linear terms (the thickness and loading noise components) is dominant only in a spatially very limited region. Then, contrary to popular belief and regardless of the low blade rotational speed, a reliable hydroacoustic analysis of a marine propeller cannot put aside the contribution of the nonlinear noise sources represented by the turbulence and vorticity three-dimensional fields and requires the computation of the FWH quadrupole source terms.

The MIPAS instrument on the ENVISAT satellite has provided vertical profiles of the atmospheric composition on a global scale for almost ten years. The MIPAS mission is divided in two phases, the full resolution phase, from 2002 to 2004, and the optimized resolution phase, from 2005 to 2012, which is characterized by a finer vertical and horizontal sampling attained through a reduction of the spectral resolution. While the description and characterization of the products of the ESA processor for the full resolution phase has been already described in previous papers, in this paper we focus on the performances of the latest version of the ESA processor, named ML2PP V6, which has been used for reprocessing the entire mission. The ESA processor had to perform the operational near real time analysis of the observations and its products needed to be available for data assimilation. Therefore, it has been designed for fast, continuous and automated analysis of observations made in quite different atmospheric conditions and for a minimum use of external constraints in order to avoid biases in the products. The dense vertical sampling of the measurements adopted in the second phase of the MIPAS mission resulted in sampling intervals finer than the instantaneous field of view of the instrument. Together with the choice of a retrieval grid aligned with the vertical sampling of the measurements, this made ill-conditioned the retrieval formalism of the MIPAS operational processor. This problem has been handled with minimal changes to the original retrieval approach but with significant improvements nonetheless. The Levenberg-Marquardt method, already present in the retrieval scheme for its capability to provide fast convergence for non-linear problems, is now also exploited for the reduction of the ill-conditioning of the inversion. An expression specifically designed for the regularizing Levenberg-Marquardt method has been implemented for the computation of the covariance matrices and averaging kernels of the retrieved products. The regularization of the Levenberg-Marquardt method is controlled by the convergence criteria and is deliberately kept weak. The resulting oscillations of the retrieved profile are a-posteriori damped by an innovative self-adapting Tikhonov regularization. The convergence criteria and the weakness of the self-adapting regularization ensure that minimum constraints are used and the best vertical resolution obtainable from the measurements is achieved in all atmospheric conditions. Random and systematic errors, as well as vertical and horizontal resolution are compared in the two phases of the mission for all products, namely: temperature, H2O, O3, HNO3, CH4, N2O, NO2, CFC-11, CFC-12, N2O5 and ClONO2. The use in the two phases of the mission of different optimized sets of spectral intervals ensures that, despite the different spectral resolutions, comparable performances are obtained in the whole MIPAS mission in terms of random and systematic errors, while the vertical resolution and the horizontal resolution are significantly better in the case of the optimized resolution measurements.

In areas of difficult access, such as the arctic ones, the extraction of inter- est zones (e.g. glaciers) from satellite images may be a valuable way to study and monitor their status . This work faces in particular the prob- lem of detecting different zones of glaciers from SAR (Synthetic Aperture Radar) images. In the polar regions the use of the SAR system is funda- mental because it works independently of weather and daylight. Segmentation is a process that allows an image to be divided into disjoint zones in such a way that each extracted area contains homogeneous char- acteristics. The numerical approach, here applied to detect glacier zones, is based on moving boundary modelling and is described by the eikonal equation. The upwind finite difference approximation of the eikonal equa- tion is solved by a fast marching technique, that starts from seed points in the region of interest and generates a front which evolves until the bound- ary of the region is identified. Results from segmentation of glacier images in the Svalbard archipelago acquired by ERS2 SAR (Synthetic Aperture Radar) and Envisat (ESA Environmental Satellite) ASAR (Advanced Synthetic Aperture Radar) are presented and discussed.

The effect of the nitrification inhibitor 3,4-dimethylphyrazole phosphate (DMPP) on N-fertilized crop growth and soil N2O emissions were studied at two experimental sites in Southern Italy, characterised by a Mediterranean climate and different soil texture. The experiments were a randomized block design of two treatments: crop fertilized with NH4NO3 (considered the control treatment) or amended with DMPP plus NH4NO3 (considered the DMPP treatment). ANOVA was performed to assess differences between treatments and fertilization periods whereas simple and multiple linear regressions were performed in order to assess the effect of the soil-related in-dependent variables on soil gases emissions. Growth of potato plants fertilized with DMPP-added nitrogen was enhanced compared to control plants, whereas no benefit on maize plants grown during summer was observed. N2O emissions measured from soil to potato after the first fertilization with DMPP-added nitrogen was reduced during winter, but was higher than control after the second fertilizer application in spring, leading to comparable N2O emission factors (EF1) between treatments. In maize N2O emissions and EF1 were lower for DMPP compared to control treatment. The effectiveness of reduction in soil N2O emission was influenced by soil temperature and water-filled pore space (WFPS) in both experimental sites. However, the overall effect of WFPS was contrasting as N2O emissions were decreased in potato and enhanced in maize.

MIPAS measurements on ENVISAT represents a unique database for the study of atmospheric composition and of the time variation of atmospheric constituents and trends, in combination with other data. With the end of the ENVISAT mission, the importance of this decadal set of measurements justifies any efforts for their full exploitation. The maintenance and the upgrade of the ESA processor are made in the frame of the Quality Working Group, where a fruitful collaboration between L1, L2 and validation teams can be exploited. This collaboration is essential to pursue improvements in the accuracy of the products and their characterization. Recently a new version of the Level 2 processor (ML2PP V7) has been finalized, containing a new approach for handling continuum capable of making the retrieval more stable, a new selection of spectral intervals selected for the analysis of the full resolution measurements aimed to reduce the bias between full resolution and optimized resolution measurements, the regularization of the H2O profiles, the products of five new species (CFC-22, CFC-14, HCN, COF2, CCl4). The addition of these 5 species leads to 15 the number of species processed by the operational processor, but the list of retrieved species can be further enlarged. The latest improvements implemented in the ESA processor and the results of the feasibility studies for additional upgrades will be presented and discussed.

A new color quantization algorithm, CQ, is presented, which includes two phases. The first phase reduces the number of colors by reducing the spatial resolution of the input image. The second phase furthermore reduces the number of colors by performing color clustering guided by distance information. Then, color mapping completes the process. The algorithm has been tested on a large number of color images with different size and color distribution, and the performance has been compared to the performance of other algorithms in the literature.

We complete the analytical determination, at the 4th post-Newtonian approximation, of the main radial potential describing the gravitational interaction of two bodies within the effective one-body formalism. The (nonlogarithmic) coefficient a5(?) measuring this 4th post-Newtonian interaction potential is found to be linear in the symmetric mass ratio ?. Its ?-independent part a5(0) is obtained by an analytical gravitational self-force calculation that unambiguously resolves the formal infrared divergencies which currently impede its direct post-Newtonian calculation. Its ?-linear part a5(?)-a5(0) is deduced from recent results of Jaranowski and Schäfer, and is found to be significantly negative.