IFN stimulated gene expression in the liver is a better predictor of treatment response in chronic hepatitis c than the IL28b (IFN lambda 3) genotype

Background: Therapy of chronic hepatitis C (CHC) with pegIFNa/ribavirin achieves sustained virologic response (SVR) in ~55%. Pre-activation of the endogenous interferon system in the liver is associated non-response (NR). Recently, genome-wide association studies described associations of allelic variants near the IL28B (IFNλ3) gene with treatment response and with spontaneous clearance of the virus. We investigated if the IL28B genotype determines the constitutive expression of IFN stimulated genes (ISGs) in the liver of patients with CHC. Methods: We genotyped 93 patients with CHC for 3 IL28B single nucleotide polymorphisms (SNPs, rs12979860, rs8099917, rs12980275), extracted RNA from their liver biopsies and quantified the expression of IL28B and of 8 previously identified classifier genes which discriminate between SVR and NR (IFI44L, RSAD2, ISG15, IFI22, LAMP3, OAS3, LGALS3BP and HTATIP2). Decision tree ensembles in the form of a random forest classifier were used to calculate the relative predictive power of these different variables in a multivariate analysis. Results: The minor IL28B allele (bad risk for treatment response) was significantly associated with increased expression of ISGs, and, unexpectedly, with decreased expression of IL28B. Stratification of the patients into SVR and NR revealed that ISG expression was conditionally independent from the IL28B genotype, i.e. there was an increased expression of ISGs in NR compared to SVR irrespective of the IL28B genotype. The random forest feature score (RFFS) identified IFI27 (RFFS = 2.93), RSAD2 (1.88) and HTATIP2 (1.50) expression and the HCV genotype (1.62) as the strongest predictors of treatment response. ROC curves of the IL28B SNPs showed an AUC of 0.66 with an error rate (ERR) of 0.38. A classifier with the 3 best classifying genes showed an excellent test performance with an AUC of 0.94 and ERR of 0.15. The addition of IL28B genotype information did not improve the predictive power of the 3-gene classifier. Conclusions: IL28B genotype and hepatic ISG expression are conditionally independent predictors of treatment response in CHC. There is no direct link between altered IFNλ3 expression and pre-activation of the endogenous system in the liver. Hepatic ISG expression is by far the better predictor for treatment response than IL28B genotype

Snappy App: a mobile continuous performance test with physical activity measurement for assessing Attention Deficit Hyperactivity Disorder

A Continuous Performance Test (CPT) was incorporated into a smartphone application (App) to measure three symptom domains associated with Attention Deficit Hyperactivity Disorder (ADHD); attention, impulsivity and hyperactivity. The App was pilot tested on 11 healthy adults over three test-ing sessions. No differences in performance were found between testing ses-sions suggesting good test consistency. A decrement in performance over time was only found for one measure of attention and on one testing session. The CPT showed some sensitivity to ADHD-related symptoms where self-reported impulsive behaviour was related to the CPT measures of impulsivity and activi-ty. User acceptability was good although some design improvements were sug-gested. Further pilot testing of the App in a clinical population is needed

Coherence Time Effects on J/psi Production and Suppression in Relativistic Heavy Ion Collisions

Using a coherence time extracted from high precision proton-nucleus Drell-Yan measurements and a nuclear absorption cross section extracted from pA charmonium production experiments, we study J/psi production and absorption in nucleus-nucleus collisions. We find that coherence time effects are large enough to affect the measured J/psi-to-Drell-Yan ratio. The S+U data at 200A GeV/c measured by NA38 are reproduced quantitatively without the introduction of any new parameters. However, when compared with recent NA50 measurements for Pb+Pb at 158A GeV/c, the data is not reproduced in trend or in magnitude.Comment: 8 pages, 2 figure

Thermal photons as a measure for the rapidity dependence of the temperature

The rapidity distribution of thermal photons produced in Pb+Pb collisions at CERN-SPS energies is calculated within scaling and three-fluid hydrodynamics. It is shown that these scenarios lead to very different rapidity spectra. A measurement of the rapidity dependence of photon radiation can give cleaner insight into the reaction dynamics than pion spectra, especially into the rapidity dependence of the temperature.Comment: 3 Figure

Resonances of low orders in the planetary system of HD37124

The full set of published radial velocity data (52 measurements from Keck + 58 ones from ELODIE + 17 ones from CORALIE) for the star HD37124 is analysed. Two families of dynamically stable high-eccentricity orbital solutions for the planetary system are found. In the first one, the outer planets c and d are trapped in the 2/1 mean-motion resonance. The second family of solutions corresponds to the 5/2 mean-motion resonance between these planets. In both families, the planets are locked in (or close to) an apsidal corotation resonance. In the case of the 2/1 MMR, it is an asymmetric apsidal corotation (with the difference between the longitudes of periastra $\Delta\omega\sim 60^\circ$), whereas in the case of the 5/2 MMR it is a symmetric antialigned one ($\Delta\omega = 180^\circ$). It remains also possible that the two outer planets are not trapped in an orbital resonance. Then their orbital eccentricities should be relatively small (less than, say, 0.15) and the ratio of their orbital periods is unlikely to exceed $2.3-2.5$.Comment: 28 pages, 10 figures, 3 tables; Accepted to Celestial Mechanics and Dynamical Astronom

Markovian MC simulation of QCD evolution at NLO level with minimum k_T

We present two Monte Carlo algorithms of the Markovian type which solve the modified QCD evolution equations at the NLO level. The modifications with respect to the standard DGLAP evolution concern the argument of the strong coupling constant alpha_S. We analyze the z - dependent argument and then the k_T - dependent one. The evolution time variable is identified with the rapidity. The two algorithms are tested to the 0.05% precision level. We find that the NLO corrections in the evolution of parton momentum distributions with k_T - dependent coupling constant are of the order of 10 to 20%, and in a small x region even up to 30%, with respect to the LO contributions.Comment: 32 pages, 9 pdf figure

Observing many body effects on lepton pair production from low mass enhancement and flow at RHIC and LHC energies

The $\rho$ spectral function at finite temperature calculated using the real-time formalism of thermal field theory is used to evaluate the low mass dilepton spectra. The analytic structure of the $\rho$ propagator is studied and contributions to the dilepton yield in the region below the bare $\rho$ peak from the different cuts in the spectral function are discussed. The space-time integrated yield shows significant enhancement in the region below the bare $\rho$ peak in the invariant mass spectra. It is argued that the variation of the inverse slope of the transverse mass ($M_T$) distribution can be used as an efficient tool to predict the presence of two different phases of the matter during the evolution of the system. Sensitivity of the effective temperature obtained from the slopes of the $M_T$ spectra to the medium effects are studied

Anaerobic Microbial Degradation of Hydrocarbons: From Enzymatic Reactions to the Environment

Hydrocarbons are abundant in anoxic environments and pose biochemical challenges to their anaerobic degradation by microorganisms. Within the framework of the Priority Program 1319, investigations funded by the Deutsche Forschungsgemeinschaft on the anaerobic microbial degradation of hydrocarbons ranged from isolation and enrichment of hitherto unknown hydrocarbon-degrading anaerobic microorganisms, discovery of novel reactions, detailed studies of enzyme mechanisms and structures to process-oriented in situ studies. Selected highlights from this program are collected in this synopsis, with more detailed information provided by theme-focused reviews of the special topic issue on 'Anaerobic biodegradation of hydrocarbons' [this issue, pp. 1-244]. The interdisciplinary character of the program, involving microbiologists, biochemists, organic chemists and environmental scientists, is best exemplified by the studies on alkyl-/arylalkylsuccinate synthases. Here, research topics ranged from in-depth mechanistic studies of archetypical toluene-activating benzylsuccinate synthase, substrate-specific phylogenetic clustering of alkyl-/arylalkylsuccinate synthases (toluene plus xylenes, p-cymene, p-cresol, 2-methylnaphthalene, n-alkanes), stereochemical and co-metabolic insights into n-alkane-activating (methylalkyl) succinate synthases to the discovery of bacterial groups previously unknown to possess alkyl-/arylalkylsuccinate synthases by means of functional gene markers and in situ field studies enabled by state-of-the-art stable isotope probing and fractionation approaches. Other topics are Mo-cofactor-dependent dehydrogenases performing O-2-independent hydroxylation of hydrocarbons and alkyl side chains (ethylbenzene, p-cymene, cholesterol, n-hexadecane), degradation of p-alkylated benzoates and toluenes, glycyl radical-bearing 4-hydroxyphenylacetate decarboxylase, novel types of carboxylation reactions (for acetophenone, acetone, and potentially also benzene and naphthalene), W-cofactor-containing enzymes for reductive dearomatization of benzoyl-CoA (class II benzoyl-CoA reductase) in obligate anaerobes and addition of water to acetylene, fermentative formation of cyclohexanecarboxylate from benzoate, and methanogenic degradation of hydrocarbons

Hadronic final states in deep-inelastic scattering with Sherpa

We extend the multi-purpose Monte-Carlo event generator Sherpa to include processes in deeply inelastic lepton-nucleon scattering. Hadronic final states in this kinematical setting are characterised by the presence of multiple kinematical scales, which were up to now accounted for only by specific resummations in individual kinematical regions. Using an extension of the recently introduced method for merging truncated parton showers with higher-order tree-level matrix elements, it is possible to obtain predictions which are reliable in all kinematical limits. Different hadronic final states, defined by jets or individual hadrons, in deep-inelastic scattering are analysed and the corresponding results are compared to HERA data. The various sources of theoretical uncertainties of the approach are discussed and quantified. The extension to deeply inelastic processes provides the opportunity to validate the merging of matrix elements and parton showers in multi-scale kinematics inaccessible in other collider environments. It also allows to use HERA data on hadronic final states in the tuning of hadronisation models.Comment: 32 pages, 22 figure