How to Predict Molecular Interactions between Species?

Organisms constantly interact with other species through physical contact which leads to chan-ges on the molecular level, for example the transcriptome. These changes can be monitored forall genes, with the help of high-throughput experiments such as RNA-seq or microarrays. Theadaptation of the gene expression to environmental changes within cells is mediated throughcomplex gene regulatory networks. Often, our knowledge of these networks is incomplete. Netw-ork inference predicts gene regulatory interactions based on transcriptome data. An emergingapplication of high-throughput transcriptome studies are dual transcriptomics experiments. Here,the transcriptome of two or more interacting species is measured simultaneously. Based ona dual RNA-seq data set of murine dendritic cells infected with the fungal pathogen Candidaalbicans, the software tool NetGenerator was applied to predict an inter-species gene regulatorynetwork. To promote further investigations of molecular inter-species interactions, we recentlydiscussed dual RNA-seq experiments for host-pathogen interactions and extended the appliedtool NetGenerator (Schulze et al., 2015). The updated version of NetGenerator makes use ofmeasurement variances in the algorithmic procedure and accepts gene expression time seriesdata with missing values. Additionally, we tested multiple modeling scenarios regarding the stimulifunctions of the gene regulatory network. Here, we summarize the work by Schulze et al. (2015)and put it into a broader context. We review various studies making use of the dual transcriptomicsapproach to investigate the molecular basis of interacting species. Besides the application tohost-pathogen interactions, dual transcriptomics data are also utilized to study mutualistic andcommensalistic interactions. Furthermore, we give a short introduction into additional approachesfor the prediction of gene regulatory networks and discuss their application to dual transcriptomicsdata. We conclude that the application of network inference on dual-transcriptomics data is apromising approach to predict molecular inter-species interactions

On Comments in Visual Languages

Visual languages based on node-link diagrams can be used to develop software and, like textual languages, offer the possibility to write explanatory comments. Which node a comment refers to is usually not made explicit, but is implicitly clear to readers through placement and content. While automatic layout algorithms can make working with diagrams more productive, they tend to destroy such implicit clues because they are not aware of them and thus do not preserve the relative placement of comments and the nodes they refer to. Implicit clues thus need to be inferred and made explicit to be taken into account by layout algorithms. This is what we call the comment attachment problem. In this paper, we improve upon a previous paper on the subject [9], introducing further heuristics that aim to describe relations between comments and nodes. Based on an analysis of comment placement in a set of example diagrams, we develop a general comment attachment framework and evaluate the quality of its inferred attachments

Automatic Layout and Label Management for UML Sequence Diagrams

Sequence diagrams belong to the most commonly used types of UML diagrams. There is research on desirable aesthetics, but to our knowledge no published layout algorithms, although several have been developed. This might be due to the rigid specifcation of sequence diagrams that seems to make laying them out quite easy. However, as we argue here, naive algorithms do not always produce desirable solutions. We present a layout algorithm that can compute the order of lifelines according to different optimization criteria. We also look at the problem of diagram size by introducing vertical compaction to sequence diagrams and by applying label management to compact them horizontally. We evaluate our methods with 50 real-world sequence diagrams

Drawing Layered Hypergraphs

Orthogonally drawn hypergraphs have important applications, e.g. in actor-oriented data flow diagrams for modeling complex software systems. Graph drawing algorithms based on the approach by Sugiyama et al. place nodes into consecutive layers and try to minimize the number of edge crossings by finding suitable orderings of the nodes in each layer. With orthogonal hyperedges, however, the exact number of crossings is not determined until the edges are actually routed in a later phase of the algorithm, which makes it hard to evaluate the quality of a given node ordering beforehand. In this report, we present and evaluate two crossing counting algorithms that predict the number of crossings between orthogonally routed hyperedges much more accurately than previous methods. We also describe methods for routing hyperedges that span multiple layers and for handling junction points

Using One-Dimensional Compaction for Smaller Graph Drawings

We review the technique of one-dimensional compaction and use it as part of two new methods tackling problems in the context of automatic diagram layout: First, a postprocessing of the layer-based layout algorithm, also known as Sugiyama layout, and second a placement algorithm for connected components with external extensions. We apply our methods to dataflow diagrams from practical applications and find that the first method significantly reduces the width of left-to-right drawn diagrams. The second method allows to properly arrange disconnected graphs that have hierarchycrossing edges. Keywords: one-dimensional compaction, diagram layout, layer-based layout, Sugiyama layout, disconnected graphs, dataflow diagram

Activated complement C3: A potentially novel predictor of progressive IgA nephropathy

Activated complement C3: A potentially novel predictor of progressive IgA nephropathy. In the search for a serologic marker of disease activity, we measured concentrations of activated C3 (actC3, that is, neoantigens developing after C3 activation on breakdown products), C4-C3 complexes and soluble C5b-9 (sC5b-9) in one or two plasma samples from adult patients with IgA nephropathy (IgAN, N = 50) or Henoch-Schönlein purpura (HSP, N = 4). As controls, 20 patients with non-immune renal disease, but comparable age, degree of proteinuria, renal dysfunction and prevalence of hypertension were studied. Compared to controls, actC3 levels were elevated in 30% of the patients with IgAN and one of the HSP patients. C4-C3 complexes were elevated in only 8% of the IgAN patients, and sC5b-9 levels were within the control range in all IgAN and HSP patients. In IgAN patients with elevated actC3 levels, proteinuria and hematuria were more pronounced than in those with normal levels. Elevated plasma concentrations of actC3 at the first presentation correlated with subsequent deterioration of renal function both in patients with initially normal and already impaired renal function (r = -0.56, N = 44, P = 0.003). The five IgAN patients with elevated actC3 on both occasions of obtaining plasma showed the most rapid loss of renal function. We conclude that mainly alternative pathway complement activation can be demonstrated in patients with IgAN and HSP. In IgAN patients the presence of complement activation is associated with more severe renal disease. Further studies are warranted to examine the clinical usefulness of actC3 as a predictor of the subsequent course of IgAN

a route towards defined surface functionalization

We investigate the surface-catalyzed dissociation of the archetypal molecular switch azobenzene on the Cu(111) surface. Based on X-ray photoelectron spectroscopy, normal incidence X-ray standing waves and density functional theory calculations a detailed picture of the coverage-induced formation of phenyl nitrene from azobenzene is presented. Furthermore, a comparison to the azobenzene/Ag(111) interface provides insight into the driving force behind the dissociation on Cu(111). The quantitative decay of azobenzene paves the way for the creation of a defect free, covalently bonded monolayer. Our work suggests a route of surface functionalization via suitable azobenzene derivatives and the on surface synthesis concept, allowing for the creation of complex immobilized molecular systems

Hyperons and massive neutron stars: the role of hyperon potentials

The constituents of cold dense matter are still far from being understood. However, neutron star observations such as the recently observed pulsar PSR J1614-2230 with a mass of 1.97+/-0.04 M_solar help to considerably constrain the hadronic equation of state (EoS). We systematically investigate the influence of the hyperon potentials on the stiffness of the EoS. We find that they have but little influence on the maximum mass compared to the inclusion of an additional vector meson mediating repulsive interaction amongst hyperons. The new mass limit can only be reached with this additional meson regardless of the hyperon potentials. Further, we investigate the impact of the nuclear compression modulus and the effective mass of the nucleon at saturation density on the high density regime of the EoS. We show that the maximum mass of purely nucleonic stars is very sensitive to the effective nucleon mass but only very little to the compression modulus.Comment: 24 pages, 8 figure

Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension

Pulmonary hypertension (PH) is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg) is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague–Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose). There were three experimental groups: sham-treated controls (control group, n = 11), MCT-induced PH (MCT group, n = 11) and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13). ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys) was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg) compared to the control group (41 ± 15 mmHg, p = 0.002) accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001). Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01). Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006) and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022). PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH