Revealing differences in gene network inference algorithms on the network level by ensemble methods

Motivation: The inference of regulatory networks from large-scale expression data holds great promise because of the potentially causal interpretation of these networks. However, due to the difficulty to establish reliable methods based on observational data there is so far only incomplete knowledge about possibilities and limitations of such inference methods in this context.

Results: In this article, we conduct a statistical analysis investigating differences and similarities of four network inference algorithms, ARACNE, CLR, MRNET and RN, with respect to local network-based measures. We employ ensemble methods allowing to assess the inferability down to the level of individual edges. Our analysis reveals the bias of these inference methods with respect to the inference of various network components and, hence, provides guidance in the interpretation of inferred regulatory networks from expression data. Further, as application we predict the total number of regulatory interactions in human B cells and hypothesize about the role of Myc and its targets regarding molecular information processing.

Spatial dynamics of the light emission from a microplasma array

The spatial dynamics of the optical emission from an array of 50x50 individual microplasma devices is reported. The array is operated in noble gas at atmospheric pressure with an ac voltage. The optical emission is analyzed with phase and space resolution. It has been found that the emission is not continuous over the entire ac period, it occurs only twice in each cycle. Each of the observed emission phases shows a self-pulsing of the discharge, with several bursts of emission of a fixed width and repetition rate. Cross-talk between the individual devices can be observed through spatially resolved measurements. (C) 2008 American Institute of Physics.

Received signal strength in large-scale wireless relay sensor network: a stochastic ray approach

The authors consider a point percolation lattice representation of a large-scale wireless relay sensor network (WRSN) deployed in a cluttered environment. Each relay sensor corresponds to a grid point in the random lattice and the signal sent by the source is modelled as an ensemble of photons that spread in the space, which may 'hit' other sensors and are 'scattered' around. At each hit, the relay node forwards the received signal to its nearest neighbour through direction-selective relaying. The authors first derive the distribution that a relay path reaches a prescribed location after undergoing certain number of hops. Subsequently, a closed-form expression of the average received signal strength (RSS) at the destination can be computed as the summation of all signal echoes' energy. Finally, the effect of the anomalous diffusion exponent ß on the mean RSS in a WRSN is studied, for which it is found that the RSS scaling exponent e is given by (3ß-1)/ß. The results would provide useful insight into the design and deployment of large-scale WRSNs in future. © 2011 The Institution of Engineering and Technology.

Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis

We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P <5 × 10(-8)), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r(2) > 0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r(2) > 0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.

Lead contamination and associated disease in captive and reintroduced red kites Milvus milvus in England

Since 1989, a red kite Milvus milvus reintroduction programme has been underway in the United Kingdom, with 4-6 week old nestlings brought into captivity and held for 6-8 weeks before reintroduction. As scavengers, red kites may consume unretrieved game, and ingest shot or lead (Pb) fragments in their prey's flesh. We evaluated exposure to Pb in captive and wild red kites by taking blood samples from 125 captive young red kites prior to release, through analysing 264 pellets (regurgitated by wild birds) collected from under a roost site, and analysing Pb concentrations in livers and/or bones of 87 red kites found dead between 1995 and 2003. Lead isotope analyses of livers were also conducted in an effort to identify Pb exposure routes. Forty-six (36.8%) kites sampled prior to release had elevated blood Pb concentrations (201-3340 microg l(-1)). The source of this Pb was probably small fragments of lead ammunition in the carcasses of birds or mammals either fed to the nestlings by their parents or, more likely, subsequently whilst in captivity. Once released, kites were also exposed to lead shot in their food, and a minimum of 1.5-2.3% of regurgitated pellets contained Pb gunshot. Seven of 44 red kites found dead or that were captured sick and died within a few days had elevated (>6 mg kg(-1) dry weight [d.w.]) liver Pb concentrations, and six of these (14%) had concentrations of >15 mg kg(-1) d.w., compatible with fatal Pb poisoning. Post-mortem analyses indicated that two of these birds had died of other causes (poisoning by rodenticide and a banned agricultural pesticide); the remaining four (9%) probably died of Pb poisoning. Bone samples from 86 red kites showed a skewed distribution of Pb concentration, and 18 samples (21%) had Pb concentrations >20 mg kg(-1) d.w., indicating elevated exposure to Pb at some stage in the birds' life. Lead isotopic signatures (Pb (208/206); Pb (206/207)) in liver samples of the majority of kites were compatible with those found in lead shot extracted from regurgitated pellets. Lead isotope ratios found in the livers of kites with very low Pb concentrations were distinct from UK petrol Pb isotopic signatures, indicating that birds were exposed to little residual petrol Pb. We conclude that the primary source of Pb to which red kites are exposed is lead ammunition (shotgun pellets or rifle bullets), or fragments thereof, in their food sources; in some cases exposure appears sufficient to be fatal. We make recommendations to reduce Pb poisoning in both captive and wild red kites and other scavenging species.

An in situ spatially resolved method to probe gas phase reactions through a fixed bed catalyst

A new method to spatially probe heterogeneous catalysed reactions within a packed bed of catalyst has been developed. The spatial resolution is achieved using a stationary perforated capillary coupled to a mass spectrometer while the catalyst bed is moved. The oxidation of CO promoted by H-2 over a Pd catalyst has been used to demonstrate the technique.

Arsenate causes differential acute toxicity to two P-deprived genotypes of rice seedlings (Oryza sativa L.)

Significant genotypic difference in response to arsenate toxicity in rice (Oryza sativa) was investigated in root elongation, arsenate uptake kinetics, physiological and biochemical response and arsenic (As) speciation. Uptake kinetics data showed that P-deprived genotype 94D-54 had a little higher As uptake than P-deprived 94D-64, but the difference was not large enough to cause acute toxicity in P-deprived 94D-54. There was no difference in tissue P concentrations between the two genotypes under P deficient conditions. In addition, arsenic speciation in plant tissues (using high performance liquid chromatography-inductively coupled plasma mass spectrometry) was not different between P pretreatments and between genotypes. P-deprived genotype 94D-54 suffered much higher stress induced by arsenate toxicity than P-deprived genotype 94D-64, in terms of lipid peroxidation, tissue H2O2 concentrations and exosmosis of K, P and As. However, P-deprived 94D-54 also had higher overproduction of enzymatic antioxidants (with higher GPX, SOD, CAT) and NPT (non-protein thiols) than P-deprived 94D-64. It appeared that, the higher sensitivity of P-deprived 94D-54 to arsenate toxicity might cause the overproduction of NPT, thus leading to the depletion of GSH and to the accumulation of H2O2. The differential sensitivity of the two genotypes has major implications for breeding rice for As affected paddy soil.

Exploring diversity through ethos in initial teacher education

This paper considers whether there is value in introducing student teachers to schools of different ethos as part of their initial teacher education. A 2-year study of undergraduate post-primary student teachers at a university college in Northern Ireland reveals that encounters with schools of different ethos can help student teachers to understand differences between schools and their visions of education, as well as correcting misunderstandings and challenging stereotypes. It is argued that as a result of experiencing diverse examples of ethos, student teachers may also be helped to understand the complexity of schools as organisations and to position themselves and their professional practice within wider debates about the aims of education and schools as communities of practice. © 2008 Elsevier Ltd. All rights reserved.

One-Electron Reduction of 2-Nitrotoluene, Nitrocyclopentane, and 1-Nitrobutane in Room Temperature Ionic Liquids: A Comparative Study of Butler–Volmer and Symmetric Marcus–Hush Theories Using Microdisk Electrodes

The voltammetry for the reduction of 2-nitrotoluene at a gold microdisk electrode is reported in two ionic liquids: trihexyltetradecylphosphonium tris(pentafluoroethyl)trifluorophosphate ([P-14,P-6,P-6,P-6][FAP]) and 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([Emim][NTf2]). The reduction of nitrocyclopentane (NCP) and 1-nitrobutane (BuN) was investigated using voltammetry at a gold microdisk electrode in the ionic liquid [P-14,P-6,P-6,P-6][FAP]. Simulated voltammograms, generated through the use of ButlerVolmer theory and symmetric MarcusHush theory, were compared to experimental data, with both theories parametrizing the data similarly well. An experimental value for the Marcusian parameter, 1 was also determined in all cases. For the reduction of 2-nitrotoluene, this was 0.5 +/- 0.1 eV in both solvents, while for NCP and BuN in [P-14,P-6,P-6,P-6][FAP], it was 2 +/- 0.1 and 5 +/- 0.1 eV, respectively. This is attributed to the localization of charge on the nitro group and the primary nitro alkyls increased interaction with the environment, resulting in a larger reorganization energy.

Rules and Stereoelectronic Guidelines for the Anionic Nucleophilic Displacement of Furanoside and Furanose O-sulfonates

Rules for predicting anionic S_N2 displacement viability in furanose and furanoside sulfonates are presented

Application of Asymmetric Marcus-Hush Theory to Voltammetry in Room-Temperature Ionic Liquids

Asymmetric MarcusHush (AMH) theory is applied for the first time in ionic solvents to model the voltammetric reduction of oxygen in 1-butyl-1-methylpyrrolidinium bis-(trifluoromethylsulfonyl)-imide and of 2-nitrotoluene (2-NT), nitrocyclopentane (NCP), and 1-nitro-butane (BuN) in trihexyltetradecylphosphonium tris(pentafluoroethyl)trifluorophosphate on a gold microdisc electrode. An asymmetry parameter, gamma, was estimated for all systems as -0.4 for the reduction of oxygen and -0.05, 0.25, and 0 +/- 0.05 for the reductions of 2-NT, NCP, and BuN, respectively, which suggests equal force constants of reactants and products in the case of 2-NT and BuN and unequal force constants for oxygen and NCP where the force constants of the oxidized species are greater than the reduced species in the case of oxygen and less than the reduced species in the case of NCP. Previously measured values for a, the Butler-Volmer transfer coefficient, reflect this in each case. Where appreciable asymmetry occurs, AMH theory was seen to parametrize the experimental data better than either Butler-Volmer or symmetric Marcus-Hush theory, allowing additionally the extraction of reorganization energy. This is the first study to provide key physical insights into electrochemical systems in room-temperature ionic liquids using AMH theory, allowing elucidation of the reorganization energies and the relative force constants of the reactants and products in each reaction.

Prevotella denticola Lipopolysaccharide from a Cystic Fibrosis Isolate Possesses a Unique Chemical Structure

We report the first complete structural characterization of the lipopolysaccharide (LPS) from a cystic fibrosis (CF) clinical isolate of Prevotella denticola (B003V1S1X). Chemical, spectroscopic, and spectrometric analyses revealed a unique rough-type LPS (LOS) structure. The structure has a highly negatively charged heptasaccharide core region containing hexoses, with the first two sugars, 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) and mannose, highly phosphorylated. Furthermore, the lipid A moiety has the typical structure for the genus Prevotella, and was also highly phosphorylated.