Background: Non-codingRNAs(ncRNAs)areemergingaskeyregulatorsofmanycellularprocessesinboth physiological and pathological states. Moreover, the constant discovery of new non-coding RNA species suggests that the study of their complex functions is still in its very early stages. This variegated class of RNA species encompasses the well-known microRNAs (miRNAs) and the most recently acknowledged long non-coding RNAs (lncRNAs). Interestingly, in the last couple of years, a few studies have shown that some lncRNAs can act as miRNA sponges, i.e. as competing endogenous RNAs (ceRNAs), able to reduce the amount of miRNAs available to target messenger RNAs (mRNAs). Results: WeproposeacomputationalapproachtoexploretheabilityoflncRNAstoactasceRNAsbyprotecting mRNAs from miRNA repression. A seed match analysis was performed to validate the underlying regression model. We built normal and cancer networks of miRNA-mediated sponge interactions (MMI-networks) using breast cancer expression data provided by The Cancer Genome Atlas. Conclusions: OurstudyhighlightsamarkedrewiringintheceRNAprogrambetweennormalandpathological breast tissue, documented by its "on/off" switch from normal to cancer, and vice-versa. This mutually exclusive activation confers an interesting character to ceRNAs as potential oncosuppressive, or oncogenic, protagonists in cancer. At the heart of this phenomenon is the lncRNA PVT1, as illustrated by both the width of its antagonist mRNAs in normal-MMI-network, and the relevance of the latter in breast cancer. Interestingly, PVT1 revealed a net binding preference towards the mir-200 family as the bone of contention with its rival mRNAs.

Duchenne muscular dystrophy (DMD) is a genetic disease that results in the death of affected boys by early adulthood. The genetic defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor effective treatment for DMD. During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has led to valuable but incomplete insights into the disease process. For example, immune cells are thought to be responsible for a significant portion of muscle cell death in the mdx mouse; however, the role and time course of the immune response in the dystrophic process have not been well described. In this paper we constructed a simple mathematical model to investigate the role of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular dystrophy. Our model suggests that the immune response contributes substantially to the muscle degeneration and regeneration processes. Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the mice, and the damaged fibers are never completely cleared. © 2014 Abdul Salam Jarrah et al.

It is coming nowadays more clear that in order to obtain a unified description of the different mechanisms governing the behavior and causality relations among the various parts of a living system, the development of comprehensive computational and mathematical models at different space and time scales is required. This is one of the most formidable challenges of modern biology characterized by the availability of huge amount of high throughput measurements. In this paper we draw attention to the importance of multiscale modeling in the framework of studies of biological systems in general and of the immune system in particular.

A Godunov scheme is derived for two-dimensional scalar conservation laws without or with source terms following ideas originally proposed by Boukadida and LeRoux [Math. Comput., 63 (1994), pp. 541-553] in the context of a staggered Lax-Friedrichs scheme. In both situations, the numerical fluxes are obtained at each interface of a uniform Cartesian computational grid just by means of the "external waves" involved in the entropy solution of the elementary two-dimensional (2D) Riemann problems; in particular, all the wave-interaction phenomena are overlooked. This restriction of the wave pattern suffices for deriving the exact numerical fluxes of the staggered Lax-Friedrichs scheme, but it furnishes only an approximation for the Godunov scheme: we show that under convenient assumptions, these flux functions are smooth and the resulting discretization process is stable under nearly optimal CFL restriction. A well-balanced extension is presented, relying on the Curl-free component of the Helmholtz decomposition of the source term. Several numerical tests against exact 2D solutions are performed for convex, nonconvex, and inhomogeneous equations and the time-evolution of the L1 truncation error is displayed.

When numerically simulating a kinetic model of an n+nn+ semiconductor device, obtaining a constant macroscopic current at steady state is still a challenging task. Part of the difficulty comes from the multiscale, discontinuous nature of both p|n junctions, which create spikes in the electric field and enclose a channel where corresponding depletion layers glue together. The kinetic formalism furnishes a model holding inside the whole domain, but at the price of strongly varying parameters. By concentrating both the electric acceleration and the linear collision terms at each interface of a Cartesian computational grid, we can treat them by means of a Godunov scheme involving two types of scattering matrices. Combining both these mechanisms into a global Smatrix can be achieved thanks to "Redheffer's star-product." Assuming that the resulting S-matrix is stochastic permits us to prove maximum principles under a mild CFL restriction. Numerical illustrations of collisional Landau damping and various n+nn+ devices are provided on coarse grids.

The numerical approximation of one-dimensional relativistic Dirac wave equations is considered within the recent framework consisting in deriving local scattering matrices at each interface of the uniform Cartesian computational grid. For a Courant number equal to unity, it is rigorously shown that such a discretization preserves exactly the (Formula presented.) norm despite being explicit in time. This construction is well-suited for particles for which the reference velocity is of the order of (Formula presented.), the speed of light. Moreover, when (Formula presented.) diverges, that is to say, for slow particles (the characteristic scale of the motion is non-relativistic), Dirac equations are naturally written so as to let a "diffusive limit" emerge numerically, like for discrete 2-velocity kinetic models. It is shown that an asymptotic-preserving scheme can be deduced from the aforementioned well-balanced one, with the following properties: it yields unconditionally a classical Schrödinger equation for free particles, but it handles the more intricate case with an external potential only conditionally (the grid should be such that (Formula presented.)). Such a stringent restriction on the computational grid can be circumvented easily in order to derive a seemingly original Schrödinger scheme still containing tiny relativistic features. Numerical tests (on both linear and nonlinear equations) are displayed. © 2014 Springer Science+Business Media Dordrecht.

Nel febbraio del 2010 nei pressi dell'abitato di Maierato, in provincia di Vibo Valentia, si è verificata una frana profonda, evoluta in colata veloce, che ha determinato una condizione di grave emergenza. Le attività di studio e indagine condotte nell'ambito dell'Ordinanza della Presidenza del Consiglio dei Ministri n. 3862/2010 ed i successivi approfondimenti, hanno evidenziato la presenza di un'antica frana nella parte sud dell'abitato, in località Vonace. In particolare, lo studio geologico-strutturale e geomorfologico ha evidenziato che si tratta di un antico scorrimento in blocco, costituito da calcare evaporitico messiniano, con movimento lungo una superficie a basso angolo, localizzata all'interno delle sottostanti marne emipelagiche tortoniano-messiniane, prossima al contatto stratigrafico tra le due unità. L'antica scarpata di frana è attualmente modellata ed il blocco di calcare evaporitico traslato si trova nella parte bassa del versante. Su base geologico-geomorfologica non sussistono elementi riconducibili ad una riattivazione dello scorrimento in blocco e un'analoga indicazione si desume dall'analisi di sensitività delle condizioni di stabilità condotta con riferimento al modello geotecnico preliminare. I tempi e le risorse necessari per continuare gli approfondimenti di studio, e la presenza in località Vonace di elementi geologico-strutturali simili a quelli riscontrati nel versante coinvolto dalla frana del febbraio 2010, suggeriscono l'opportunità di utilizzare il monitoraggio per il controllo dell'area e per individuare variazioni significative di grandezze correlabili alle condizioni di instabilità. Nella nota è pertanto illustrata una sperimentazione che vede l'utilizzo di un monitoraggio che considera l'integrazione dei dati acquisiti da misure GPS, inclinometriche e da Ground-Based SAR (GBSAR). In particolare, l'analisi delle misure eseguite fornisce indicazioni circa lo stato di attività della frana antica considerata. Le indicazioni desunte dalla sperimentazione condotta forniscono gli elementi per precisare la strategia di monitoraggio integrato, con tecniche tradizionali e tecnologie innovative, finalizzata al controllo nel medio-lungo termine delle condizioni di movimento ed alla mitigazione del rischio da frana in località Vonace. I risultati ottenuti indirizzano, inoltre, la prosecuzione degli approfondimenti di studio in corso.

The paper deals with the numerical solution of a nonstandard Sturm-Liouville boundary value problem on the half line where the coefficients of the differential terms depend on the unknown function by means of a scalar integral operator. By using a finite difference discretization, a truncated quadrature rule and an iterative procedure, we construct a numerical method, whose convergence is proved. The order of convergence and the truncation at infinity are also discussed. Finally, some numerical tests are given to show the performance of the method. © 2013 Elsevier B.V. All rights reserved.

Tidal interactions have a significant influence on the late dynamics of compact binary systems, which constitute the prime targets of the upcoming network of gravitational-wave detectors. We refine the theoretical description of tidal interactions (hitherto known only to the second post-Newtonian level) by extending our recently developed analytic self-force formalism, for extreme-mass-ratio binary systems, to the computation of several tidal invariants. Specifically, we compute, to linear order in the mass ratio and to the 7.5th post-Newtonian order, the following tidal invariants: the square and the cube of the gravitoelectric quadrupolar tidal tensor, the square of the gravitomagnetic quadrupolar tidal tensor, and the square of the gravitoelectric octupolar tidal tensor. Our high-accuracy analytic results are compared to recent numerical self-force tidal data by Dolan et al. [arXiv:1406.4890 [Phys. Rev. D (to be published)]?], and, notably, provide an analytic understanding of the light ring asymptotic behavior found by them. We transcribe our kinematical tidal-invariant results in the more dynamically significant effective one-body description of the tidal interaction energy. By combining, in a synergetic manner, analytical and numerical results, we provide simple, accurate analytic representations of the global, strong-field behavior of the gravitoelectric quadrupolar tidal factor. A striking finding is that the linear-in-mass-ratio piece in the latter tidal factor changes sign in the strong-field domain, to become negative (while its previously known second post-Newtonian approximant was always positive). We, however, argue that this will be more than compensated by a probable fast growth, in the strong-field domain, of the nonlinear-in-mass-ratio contributions in the tidal factor.

The first part of this work reviews the algebraic matricial approach to transport data inversion. It works for the convection-diffusion transport equation used for periodic signals and provides a formally exact solution, as well as a quantitative assessment of error bars. The standard methods of reconstruction infer the diffusivity D and pinch V by matching experimental data against those simulated by transport codes. These methods do not warrant the validity of either the underlying models of transport, or of the reconstructed D(r) and V(r), even when the results look reasonable. However, the adoption of automated global search algorithms based upon genetic algorithms is bound to greatly increase the probability of finding optimal solutions.

The wind effect on river water quality was illustrated by means of thermohaline measurements carried out in the Tiber River in May 2012. The survey was carried out using a boat, in stations located in the two Tiber branches: Fiumara Grande and Traiano Canal. Thermohaline variables (salinity and temperature) were used to describe the water-type patterns and to define the salt-wedge position. Although the river flow rate was rather high, saltwater intrusion happened. Wind data suggested that the more probable cause of salt-wedge intrusion was the wind action. Especially wind speeds higher than 4 m/s are able to dominate the sea current at surface layers, determining an increase in the sea level. Therefore, westerly winds determined a seawater inflow in the river mouths.

Within the complex pathological picture associated to diabetes, high glucose (HG) has ". per se" effects on cells and tissues that involve epigenetic reprogramming of gene expression. In fetal tissues, epigenetic changes occur genome-wide and are believed to induce specific long term effects. Human umbilical vein endothelial cells (HUVEC) obtained at delivery from gestational diabetic women were used to study the transcriptomic effects of chronic hyperglycemia in fetal vascular cells using Affymetrix microarrays. In spite of the small number of samples analyzed (n=6), genes related to insulin sensing and extracellular matrix reorganization were found significantly affected by HG. Quantitative PCR analysis of gene promoters identified a significant differential DNA methylation in TGFB2. Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates recent evidences suggesting that epigenetic reprogramming of gene expression occurs with persistent HG and provides a background for future investigations addressing genomic consequences of chronic HG. © 2014 Elsevier Inc.

We develop a mathematical model for a three-phase free boundary problem in one dimension that involves interactions between gas, water and ice. The dynamics are driven by melting of the ice layer, while the pressurized gas also dissolves within the meltwater. The model incorporates the Stefan condition at the water-ice interface along with Henry's law for dissolution of gas at the gas-water interface. We employ a quasi-steady approximation for the phase temperatures and then derive a series solution for the interface positions. A non-standard feature of the model is an integral free boundary condition that arises from mass conservation owing to changes in gas density at the gas-water interface, which makes the problem non-self-adjoint. We derive a two-scale asymptotic series solution for the dissolved gas concentration, which because of the non-self-adjointness gives rise to a Fourier series expansion in eigenfunctions that do not satisfy the usual orthogonality conditions. Numerical simulations of the original governing equations are used to validate series approximations.