Dynamic Influence Networks for Rule-based Models

We introduce the Dynamic Influence Network (DIN), a novel visual analytics technique for representing and analyzing rule-based models of protein-protein interaction networks. Rule-based modeling has proved instrumental in developing biological models that are concise, comprehensible, easily extensible, and that mitigate the combinatorial complexity of multi-state and multi-component biological molecules. Our technique visualizes the dynamics of these rules as they evolve over time. Using the data produced by KaSim, an open source stochastic simulator of rule-based models written in the Kappa language, DINs provide a node-link diagram that represents the influence that each rule has on the other rules. That is, rather than representing individual biological components or types, we instead represent the rules about them (as nodes) and the current influence of these rules (as links). Using our interactive DIN-Viz software tool, researchers are able to query this dynamic network to find meaningful patterns about biological processes, and to identify salient aspects of complex rule-based models. To evaluate the effectiveness of our approach, we investigate a simulation of a circadian clock model that illustrates the oscillatory behavior of the KaiC protein phosphorylation cycle.Comment: Accepted to TVCG, in pres

A Search for Dense Molecular Gas in High Redshift Infrared-Luminous Galaxies

We present a search for HCN emission from four high redshift far infrared (IR) luminous galaxies. Current data and models suggest that these high $z$ IR luminous galaxies represent a major starburst phase in the formation of spheroidal galaxies, although many of the sources also host luminous active galactic nuclei (AGN), such that a contribution to the dust heating by the AGN cannot be precluded. HCN emission is a star formation indicator, tracing dense molecular hydrogen gas within star-forming molecular clouds (n(H$_2$) $\sim 10^5$ cm$^{-3}$). HCN luminosity is linearly correlated with IR luminosity for low redshift galaxies, unlike CO emission which can also trace gas at much lower density. We report a marginal detection of HCN (1-0) emission from the $z=2.5832$ QSO J1409+5628, with a velocity integrated line luminosity of $L_{\rm HCN}'=6.7\pm2.2 \times10^{9}$ K km s$^{-1}$ pc$^2$, while we obtain 3$\sigma$ upper limits to the HCN luminosity of the $z=3.200$ QSO J0751+2716 of $L_{\rm HCN}'=1.0\times10^{9}$ K km s$^{-1}$ pc$^2$, $L_{\rm HCN}'=1.6\times10^{9}$ K km s$^{-1}$ pc$^2$ for the $z= 2.565$ starburst galaxy J1401+0252, and $L_{\rm HCN}'=1.0\times10^{10}$ K km s$^{-1}$ pc$^2$ for the $z = 6.42$ QSO J1148+5251. We compare the HCN data on these sources, plus three other high-$z$ IR luminous galaxies, to observations of lower redshift star-forming galaxies. The values of the HCN/far-IR luminosity ratios (or limits) for all the high $z$ sources are within the scatter of the relationship between HCN and far-IR emission for low $z$ star-forming galaxies (truncated).Comment: aastex format, 4 figures. to appear in the Astrophysical Journal; Revised lens magnification estimate for 1401+025

RuleVis: Constructing Patterns and Rules for Rule-Based Models

We introduce RuleVis, a web-based application for defining and editing "correct-by-construction" executable rules that model biochemical functionality, which can be used to simulate the behavior of protein-protein interaction networks and other complex systems. Rule-based models involve emergent effects based on the interactions between rules, which can vary considerably with regard to the scale of a model, requiring the user to inspect and edit individual rules. RuleVis bridges the graph rewriting and systems biology research communities by providing an external visual representation of salient patterns that experts can use to determine the appropriate level of detail for a particular modeling context. We describe the visualization and interaction features available in RuleVisand provide a detailed example demonstrating how RuleVis can be used to reason about intracellular interactions

Mitochondrial phylogenomics of the Bivalvia (Mollusca): searching for the origin and mitogenomic correlates of doubly uniparental inheritance of mtDNA

<p>Abstract</p> <p>Background</p> <p>Doubly uniparental inheritance (DUI) is an atypical system of animal mtDNA inheritance found only in some bivalves. Under DUI, maternally (F genome) and paternally (M genome) transmitted mtDNAs yield two distinct gender-associated mtDNA lineages. The oldest distinct M and F genomes are found in freshwater mussels (order Unionoida). Comparative analyses of unionoid mitochondrial genomes and a robust phylogenetic framework are necessary to elucidate the origin, function and molecular evolutionary consequences of DUI. Herein, F and M genomes from three unionoid species, <it>Venustaconcha ellipsiformis, Pyganodon grandis </it>and <it>Quadrula quadrula </it>have been sequenced. Comparative genomic analyses were carried out on these six genomes along with two F and one M unionoid genomes from GenBank (F and M genomes of <it>Inversidens japanensis </it>and F genome of <it>Lampsilis ornata</it>).</p> <p>Results</p> <p>Compared to their unionoid F counterparts, the M genomes contain some unique features including a novel localization of the <it>trnH </it>gene, an inversion of the <it>atp8-trnD </it>genes and a unique 3'coding extension of the cytochrome <it>c </it>oxidase subunit II gene. One or more of these unique M genome features could be causally associated with paternal transmission. Unionoid bivalves are characterized by extreme intraspecific sequence divergences between gender-associated mtDNAs with an average of 50% for <it>V. ellipsiformis</it>, 50% for <it>I. japanensis</it>, 51% for <it>P. grandis </it>and 52% for <it>Q. quadrula </it>(uncorrected amino acid p-distances). Phylogenetic analyses of 12 protein-coding genes from 29 bivalve and five outgroup mt genomes robustly indicate bivalve monophyly and the following branching order within the autolamellibranch bivalves: ((Pteriomorphia, Veneroida) Unionoida).</p> <p>Conclusion</p> <p>The basal nature of the Unionoida within the autolamellibranch bivalves and the previously hypothesized single origin of DUI suggest that (1) DUI arose in the ancestral autolamellibranch bivalve lineage and was subsequently lost in multiple descendant lineages and (2) the mitochondrial genome characteristics observed in unionoid bivalves could more closely resemble the DUI ancestral condition. Descriptions and comparisons presented in this paper are fundamental to a more complete understanding regarding the origins and consequences of DUI.</p

Radio continuum imaging of FIR luminous QSOs at z>6

We present sensitive imaging at 1.4 GHz of the two highest redshift far-infrared (FIR) luminous QSOs SDSS J114816.65+525150.2 (z=6.42) and SDSS J104845.05+463718.3 (z=6.2). Radio continuum emission is detected from J1148+5251 with S_{1.4} = 55 \pm 12 uJy, while J1048+4637 is marginally detected with S_{1.4} = 26 \pm 12 uJy. Comparison of the radio and FIR luminosities shows that both sources follow the radio-FIR correlation for star forming galaxies, with implied (massive) star formation rates \sim 10^3 M_sun year^{-1}, although we cannot rule-out as much as 50% of the FIR luminosity being powered by the AGN. Five bright (> 22 mJy) radio sources are detected within 8' of J1148+5251. This is a factor 30 more than expected for a random field. Two sources have SDSS redshifts, including a z = 1.633 radio loud quasar and a z = 0.05 radio galaxy. However, we do not find evidence for a galaxy cluster in the SDSS data, at least out to z = 0.2. Considering the faint SDSS magnitudes of the remaining radio sources, we conclude that the over-density of radio sources could either be a statistical fluke, or a very large scale structure (> 8 Mpc comoving) at z > 1. We also consider the possibility of gravitational lensing by the closest (in angle) bright galaxy in the SDSS data at z = 0.05, and conclude that the galaxy provides negligible magnification.Comment: aastex, 5 figures, 2 tables. to appear in the Astronomical Journa

A massive proto-cluster of galaxies at a redshift of z {\approx} 5.3

Massive clusters of galaxies have been found as early as 3.9 Billion years (z=1.62) after the Big Bang containing stars that formed at even earlier epochs. Cosmological simulations using the current cold dark matter paradigm predict these systems should descend from "proto-clusters" - early over-densities of massive galaxies that merge hierarchically to form a cluster. These proto-cluster regions themselves are built-up hierarchically and so are expected to contain extremely massive galaxies which can be observed as luminous quasars and starbursts. However, observational evidence for this scenario is sparse due to the fact that high-redshift proto-clusters are rare and difficult to observe. Here we report a proto-cluster region 1 billion years (z=5.3) after the Big Bang. This cluster of massive galaxies extends over >13 Mega-parsecs, contains a luminous quasar as well as a system rich in molecular gas. These massive galaxies place a lower limit of >4x10^11 solar masses of dark and luminous matter in this region consistent with that expected from cosmological simulations for the earliest galaxy clusters.Comment: Accepted to Nature, 16 Pages, 6 figure

Intraoperative ketorolac in high-risk breast cancer patients : A prospective, randomized, placebo-controlled clinical trial

Funding: This work is financed by grants received by PF, in the name of his institution: the Anticancer Fund (no grant number) (www.anticancerfund.org); the Belgian Society of Anaesthesia and Resuscitation (no grant number) (www.sarb.be); the Fondation Saint-Luc (no grant number) (www.uclouvain.be); the Commission du Patrimoine of the Université catholique de Louvain, St-Luc Hospital (exceptional grant, no number) (www.uclouvain.be). None of the funders had any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript except the scientific advise of GB, scientific director of the Anticancer Fund.Peer reviewedPublisher PD

Finite-Temperature Transport in Finite-Size Hubbard Rings in the Strong-Coupling Limit

We study the current, the curvature of levels, and the finite temperature charge stiffness, D(T,L), in the strongly correlated limit, U>>t, for Hubbard rings of L sites, with U the on-site Coulomb repulsion and t the hopping integral. Our study is done for finite-size systems and any band filling. Up to order t we derive our results following two independent approaches, namely, using the solution provided by the Bethe ansatz and the solution provided by an algebraic method, where the electronic operators are represented in a slave-fermion picture. We find that, in the U=\infty case, the finite-temperature charge stiffness is finite for electronic densities, n, smaller than one. These results are essencially those of spinless fermions in a lattice of size L, apart from small corrections coming from a statistical flux, due to the spin degrees of freedom. Up to order t, the Mott-Hubbard gap is \Delta_{MH}=U-4t, and we find that D(T) is finite for n<1, but is zero at half-filling. This result comes from the effective flux felt by the holon excitations, which, due to the presence of doubly occupied sites, is renormalized to \Phi^{eff}=\phi(N_h-N_d)/(N_d+N_h), and which is zero at half-filling, with N_d and N_h being the number of doubly occupied and empty lattice sites, respectively. Further, for half-filling, the current transported by any eigenstate of the system is zero and, therefore, D(T) is also zero.Comment: 15 pages and 6 figures; accepted for PR