Interleukin-18

Interleukin-18 (IL-18), a recently described member of the IL-1 cytokine superfamily, is now recognized as an important regulator of innate and acquired immune responses. IL-18 is expressed at sites of chronic inflammation, in autoimmune diseases, in a variety of cancers, and in the context of numerous infectious diseases. This short review will describe the basic biology of IL-18 and thereafter address its potential effector and regulatory role in several human disease states including autoimmunity and infection. IL-18, previously known as interferon-gamma (IFN-gamma)-inducing factor, was identified as an endotoxin-induced serum factor that stimulated IFN-gamma production by murine splenocytes [<sup>1</sup> ]. IL-18 was cloned from a murine liver cell cDNA library generated from animals primed with heat-killed Propionibacterium acnes and subsequently challenged with lipopolysaccharide [<sup>2</sup> ]. Nucleotide sequencing of murine IL-18 predicted a precursor polypeptide of 192 amino acids lacking a conventional signal peptide and a mature protein of 157 amino acids. Subsequent cloning of human IL-18 cDNA revealed 65% homology with murine IL-18 [<sup>3</sup>] and showed that both contain an unusual leader sequence consisting of 35 amino acids at their N terminus

A Bayesian space-time model for discrete spread processes on a lattice

Funding for this work was provided by GEOIDE through the Government of Canada’s Networks for Centres of Excellence program.In this article we present a Bayesian Markov model for investigating environmental spread processes. We formulate a model where the spread of a disease over a heterogeneous landscape through time is represented as a probabilistic function of two processes: local diffusion and random-jump dispersal. This formulation represents two mechanisms of spread which result in highly peaked and long-tailed distributions of dispersal distances (i.e., local and long-distance spread), commonly observed in the spread of infectious diseases and biological invasions. We demonstrate the properties of this model using a simulation experiment and an empirical case study - the spread of mountain pine beetle in western Canada. Posterior predictive checking was used to validate the number of newly inhabited regions in each time period. The model performed well in the simulation study in which a goodness-of-fit statistic measuring the number of newly inhabited regions in each time interval fell within the 95% posterior predictive credible interval in over 97% of simulations. The case study of a mountain pine beetle infestation in western Canada (1999-2009) extended the base model in two ways. First, spatial covariates thought to impact the local diffusion parameters, elevation and forest cover, were included in the model. Second, a refined definition for translocation or jump-dispersal based on mountain pine beetle ecology was incorporated improving the fit of the model. Posterior predictive checks on the mountain pine beetle model found that the observed goodness-of-fit test statistic fell within the 95% posterior predictive credible interval for 8 out of 10. years. The simulation study and case study provide evidence that the model presented here is both robust and flexible; and is therefore appropriate for a wide range of spread processes in epidemiology and ecology.PostprintPeer reviewe

Automorphisms of subgraphs obtained by deleting a pendant vertex

AbstractA pendant vertex, x, of a finite graph, G, is ∗-fixed in case every automorphism of G − x fixes the unique vertex of G adjacent to x. It is proved that “almost all” finite graphs which have pendant vertices have ∗-fixed pendant vertices. In addition finite trees which have ∗-fixed pendant vertices are characterized

The use of implicit evidence for relevance feedback in web retrieval

In this paper we report on the application of two contrasting types of relevance feedback for web retrieval. We compare two systems; one using explicit relevance feedback (where searchers explicitly have to mark documents relevant) and one using implicit relevance feedback (where the system endeavours to estimate relevance by mining the searcher's interaction). The feedback is used to update the display according to the user's interaction. Our research focuses on the degree to which implicit evidence of document relevance can be substituted for explicit evidence. We examine the two variations in terms of both user opinion and search effectiveness

Distinguishing Patterns of Charge Order: Stripes or Checkerboards

In two dimensions, quenched disorder always rounds transitions involving the breaking of spatial symmetries so, in practice, it can often be difficult to infer what form the symmetry breaking would take in the 'ideal,' zero disorder limit. We discuss methods of data analysis which can be useful for making such inferences, and apply them to the problem of determining whether the preferred order in the cuprates is 'stripes' or 'checkerboards.' In many cases we show that the experiments clearly indicate stripe order, while in others (where the observed correlation length is short), the answer is presently uncertain

Structural investigation into the threading intercalation of a chiral dinuclear ruthenium(II) polypyridyl complex through a B-DNA oligonucleotide

Herein we report the separation of the three stereoisomers of the DNA light-switch compound [{Ru(bpy)2}2(tpphz)]4+ (tpphz = tetrapyrido[3,2-a:2',3'-c:3″,2″-h:2‴,3‴-j]phenazine) by column chromatography and the characterization of each stereoisomer by X-ray crystallography. The interaction of these compounds with a DNA octanucleotide d(GCATATCG).d(CGATATGC) has been studied using NMR techniques. Selective deuteration of the bipyridyl rings was needed to provide sufficient spectral resolution to characterize structures. NMR-derived structures for these complexes show a threading intercalation binding mode with slow and chirality-dependent rates. This represents the first solution structure of an intercalated bis-ruthenium ligand. Intriguingly, we find that the binding site selectivity is dependent on the nature of the stereoisomer employed, with Λ RuII centers showing a better intercalation fit

Male frequent attenders of general practice and their help seeking preferences

Background: Low rates of health service usage by men are commonly linked to masculine values and traditional male gender roles. However, not all men conform to these stereotypical notions of masculinity, with some men choosing to attend health services on a frequent basis, for a variety of different reasons. This study draws upon the accounts of male frequent attenders of the General Practitioner's (GP) surgery, examining their help-seeking preferences and their reasons for choosing services within general practice over other sources of support. Methods: The study extends thematic analysis of interview data from the Self Care in Primary Care study (SCinPC), a large scale multi-method evaluation study of a self care programme delivered to frequent attenders of general practice. Data were collected from 34 semi-structured interviews conducted with men prior to their exposure to the intervention. Results: The ages of interviewed men ranged from 16 to 72 years, and 91% of the sample (n= 31) stated that they had a current health condition. The thematic analysis exposed diverse perspectives within male help-seeking preferences and the decision-making behind men's choice of services. The study also draws attention to the large variation in men's knowledge of available health services, particularly alternatives to general practice. Furthermore, the data revealed some men's lack of confidence in existing alternatives to general practice. Conclusions: The study highlights the complex nature of male help-seeking preferences, and provides evidence that there should be no 'one size fits all' approach to male service provision. It also provides impetus for conducting further studies into this under researched area of interest. © 2011 WPMH GmbH

Kernel Bounds for Structural Parameterizations of Pathwidth

Assuming the AND-distillation conjecture, the Pathwidth problem of determining whether a given graph G has pathwidth at most k admits no polynomial kernelization with respect to k. The present work studies the existence of polynomial kernels for Pathwidth with respect to other, structural, parameters. Our main result is that, unless NP is in coNP/poly, Pathwidth admits no polynomial kernelization even when parameterized by the vertex deletion distance to a clique, by giving a cross-composition from Cutwidth. The cross-composition works also for Treewidth, improving over previous lower bounds by the present authors. For Pathwidth, our result rules out polynomial kernels with respect to the distance to various classes of polynomial-time solvable inputs, like interval or cluster graphs. This leads to the question whether there are nontrivial structural parameters for which Pathwidth does admit a polynomial kernelization. To answer this, we give a collection of graph reduction rules that are safe for Pathwidth. We analyze the success of these results and obtain polynomial kernelizations with respect to the following parameters: the size of a vertex cover of the graph, the vertex deletion distance to a graph where each connected component is a star, and the vertex deletion distance to a graph where each connected component has at most c vertices.Comment: This paper contains the proofs omitted from the extended abstract published in the proceedings of Algorithm Theory - SWAT 2012 - 13th Scandinavian Symposium and Workshops, Helsinki, Finland, July 4-6, 201

Dynamic Programming for Graphs on Surfaces

We provide a framework for the design and analysis of dynamic programming algorithms for surface-embedded graphs on n vertices and branchwidth at most k. Our technique applies to general families of problems where standard dynamic programming runs in 2^{O(k log k)} n steps. Our approach combines tools from topological graph theory and analytic combinatorics. In particular, we introduce a new type of branch decomposition called "surface cut decomposition", generalizing sphere cut decompositions of planar graphs introduced by Seymour and Thomas, which has nice combinatorial properties. Namely, the number of partial solutions that can be arranged on a surface cut decomposition can be upper-bounded by the number of non-crossing partitions on surfaces with boundary. It follows that partial solutions can be represented by a single-exponential (in the branchwidth k) number of configurations. This proves that, when applied on surface cut decompositions, dynamic programming runs in 2^{O(k)} n steps. That way, we considerably extend the class of problems that can be solved in running times with a single-exponential dependence on branchwidth and unify/improve most previous results in this direction.Comment: 28 pages, 3 figure

2,2′:4,4′′:4′,4′′′-Quaterpyridine: synthesis, crystal-structure description, and Hirshfeld surface analysis

The title compound, 2,2′:4,4′′:4′,4′′′-quaterpyridine (Qtpy), C20H14N4, crystallizes in the triclinic P\overline{1} space group and has half of the mol­ecule in the asymmetric unit, corresponding to 4,4′-bi­pyridine (4,4′-bpy) that serves as the building block for the mol­ecule. C4,4′-bpy—N—C4,4′-bpy and/or N—C4,4′-bpy—C4,4′-bpy bond-angle parameters show that the 4,4′-bpy ligands are highly rigid, displaying values lower than the linear bond angle of 180°. In the crystal, the 4,4′-bpy units are seen to be facing each other in relatively close proximity. The most important inter­actions on the Hirshfeld Surface of the compound are C—H...N/H...N—C inter­actions (constituting 10.6% and 7.6% of the total surface)