h-multigrid agglomeration based solution strategies for discontinuous Galerkin discretizations of incompressible flow problems

In this work we exploit agglomeration based $h$-multigrid preconditioners to speed-up the iterative solution of discontinuous Galerkin discretizations of the Stokes and Navier-Stokes equations. As a distinctive feature $h$-coarsened mesh sequences are generated by recursive agglomeration of a fine grid, admitting arbitrarily unstructured grids of complex domains, and agglomeration based discontinuous Galerkin discretizations are employed to deal with agglomerated elements of coarse levels. Both the expense of building coarse grid operators and the performance of the resulting multigrid iteration are investigated. For the sake of efficiency coarse grid operators are inherited through element-by-element $L^2$ projections, avoiding the cost of numerical integration over agglomerated elements. Specific care is devoted to the projection of viscous terms discretized by means of the BR2 dG method. We demonstrate that enforcing the correct amount of stabilization on coarse grids levels is mandatory for achieving uniform convergence with respect to the number of levels. The numerical solution of steady and unsteady, linear and non-linear problems is considered tackling challenging 2D test cases and 3D real life computations on parallel architectures. Significant execution time gains are documented.Comment: 78 pages, 7 figure

PVT1: a rising star among oncogenic long non-coding RNAs

It is becoming increasingly clear that short and long noncoding RNAs critically participate in the regulation of cell growth, differentiation, and (mis)function. However, while the functional characterization of short non-coding RNAs has been reaching maturity, there is still a paucity of well characterized long noncoding RNAs, even though large studies in recent years are rapidly increasing the number of annotated ones. The long noncoding RNA PVT1 is encoded by a gene that has been long known since it resides in the well-known cancer risk region 8q24. However, a couple of accidental concurrent conditions have slowed down the study of this gene, that is, a preconception on the primacy of the protein-coding over noncoding RNAs and the prevalent interest in its neighbor MYC oncogene. Recent studies have brought PVT1 under the spotlight suggesting interesting models of functioning, such as competing endogenous RNA activity and regulation of protein stability of important oncogenes, primarily of the MYC oncogene. Despite some advancements in modelling the PVT1 role in cancer, there are many questions that remain unanswered concerning the precise molecular mechanisms underlying its functioning

Uncertainty Quantification of geochemical and mechanical compaction in layered sedimentary basins

In this work we propose an Uncertainty Quantification methodology for sedimentary basins evolution under mechanical and geochemical compaction processes, which we model as a coupled, time-dependent, non-linear, monodimensional (depth-only) system of PDEs with uncertain parameters. While in previous works (Formaggia et al. 2013, Porta et al., 2014) we assumed a simplified depositional history with only one material, in this work we consider multi-layered basins, in which each layer is characterized by a different material, and hence by different properties. This setting requires several improvements with respect to our earlier works, both concerning the deterministic solver and the stochastic discretization. On the deterministic side, we replace the previous fixed-point iterative solver with a more efficient Newton solver at each step of the time-discretization. On the stochastic side, the multi-layered structure gives rise to discontinuities in the dependence of the state variables on the uncertain parameters, that need an appropriate treatment for surrogate modeling techniques, such as sparse grids, to be effective. We propose an innovative methodology to this end which relies on a change of coordinate system to align the discontinuities of the target function within the random parameter space. The reference coordinate system is built upon exploiting physical features of the problem at hand. We employ the locations of material interfaces, which display a smooth dependence on the random parameters and are therefore amenable to sparse grid polynomial approximations. We showcase the capabilities of our numerical methodologies through two synthetic test cases. In particular, we show that our methodology reproduces with high accuracy multi-modal probability density functions displayed by target state variables (e.g., porosity).Comment: 25 pages, 30 figure

SWIM: A computational tool to unveiling crucial nodes in complex biological networks

SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called "fight-club hubs", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called "switch genes", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance. Here, we applied SWIM to a large panel of cancer datasets from The Cancer Genome Atlas, in order to highlight switch genes that could be critically associated with the drastic changes in the physiological state of cells or tissues induced by the cancer development. We discovered that switch genes are found in all cancers we studied and they encompass protein coding genes and non-coding RNAs, recovering many known key cancer players but also many new potential biomarkers not yet characterized in cancer context. Furthermore, SWIM is amenable to detect switch genes in different organisms and cell conditions, with the potential to uncover important players in biologically relevant scenarios, including but not limited to human cancer

Computational analysis identifies a sponge interaction network between long non-coding RNAs and messenger RNAs in human breast cancer

Background: Non-coding RNAs (ncRNAs) are emerging as key regulators of many cellular processes in both 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: We propose a computational approach to explore the ability of lncRNAs to act as ceRNAs by protecting 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: Our study highlights a marked rewiring in the ceRNA program between normal and pathological 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. © 2014 Paci et al.; licensee BioMed Central Ltd

Il De modo audiendi confessiones di Heinrich Lur e la penitenza sacramentale nel basso medioevo

Since the central centuries of the Middle Ages the sacrament of penance became one of the central aspects of religious life and Christian practice. To help the clergy tasked with pastoral care in listening penitents’ confessions manuals were penned, which are to this day not much studied. The analysis of one of these texts, the De modo audiendi confessiones of Heinrich Lur, canon in the cathedral of Trento around the half of the fifteenth century, is the occasion to reflect on what in the late Middle Ages revolved around the administration of sacramental penance, in regards to theology and canon law as well as pastoral care