Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology

Background Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. Methods We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions. Results Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles. SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders. Conclusion Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis. Keywords: Epigenetics; Whole genome array analysis; Balkan endemic nephropathy

A TEX 86 lake record suggests simultaneous shifts in temperature in Central Europe and Greenland during the last deglaciation

High-resolution quantitative temperature records from continents covering glacial to interglacial transitions are scarce but important for understanding the climate system. We present the first decadal resolution record of continental temperatures in Central Europe during the last deglaciation (similar to 14,60010,600cal. yrB.P.) based on the organic geochemical palaeothermometer TEX86. The TEX86-inferred temperature record from Lake Lucerne (Vierwaldstattersee, Switzerland) reveals typical oscillations during the Late Glacial Interstadial, followed by an abrupt cooling of 2 degrees C at the onset of Younger Dryas and a rapid warming of 4 degrees C at the onset of the Holocene, within less than 350years. The remarkable resemblance with the Greenland and regional stable oxygen isotope records suggests that temperature changes in continental Europe were dominated by large-scale reorganizations in the northern hemispheric climate system.

Estimating Annual CO2 Flux for Lutjewad Station Using Three Different Gap-Filling Techniques

Long-term measurements of CO2 flux can be obtained using the eddy covariance technique, but these datasets are affected by gaps which hinder the estimation of robust long-term means and annual ecosystem exchanges. We compare results obtained using three gap-fill techniques: multiple regression (MR), multiple imputation (MI), and artificial neural networks (ANNs), applied to a one-year dataset of hourly CO2 flux measurements collected in Lutjewad, over a flat agriculture area near the Wadden Sea dike in the north of the Netherlands. The dataset was separated in two subsets: a learning and a validation set. The performances of gap-filling techniques were analysed by calculating statistical criteria: coefficient of determination (R2), root mean square error (RMSE), mean absolute error (MAE), maximum absolute error (MaxAE), and mean square bias (MSB). The gap-fill accuracy is seasonally dependent, with better results in cold seasons. The highest accuracy is obtained using ANN technique which is also less sensitive to environmental/seasonal conditions. We argue that filling gaps directly on measured CO2 fluxes is more advantageous than the common method of filling gaps on calculated net ecosystem change, because ANN is an empirical method and smaller scatter is expected when gap filling is applied directly to measurements.

Measurement of the high-mass Drell–Yan differential cross-section in pp collisions at with the ATLAS detector

This Letter reports a measurement of the high-mass Drell-Yan differential cross-section in proton-proton collisions at a centre-of-mass energy of 7 TeV at the LHC. Based on an integrated luminosity of 4.9 fb^-^1, the differential cross-section in the Z/@c^@?->e^+e^- channel is measured with the ATLAS detector as a function of the invariant mass, m_e_e, in the range 11625 GeV and pseudorapidity |@h|<2.5. A comparison is made to various event generators and to the predictions of perturbative QCD calculations at next-to-next-to-leading order.

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H --> gamma-gamma, H --> ZZ* --> 4 leptons and H --> WW --> 2 leptons + 2 neutrinos. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of 7 TeV and 8 TeV, corresponding to an integrated luminosity of about 25/fb. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson.

Dynamics of isolated-photon plus jet production in pp collisions at with the ATLAS detector

The dynamics of isolated-photon plus jet production in pp collisions at a centre-of-mass energy of 7 TeV has been studied with the ATLAS detector at the LHC using an integrated luminosity of 37 pb^-^1. Measurements of isolated-photon plus jet bin-averaged cross sections are presented as functions of photon transverse energy, jet transverse momentum and jet rapidity. In addition, the bin-averaged cross sections as functions of the difference between the azimuthal angles of the photon and the jet, the photon-jet invariant mass and the scattering angle in the photon-jet centre-of-mass frame have been measured. Next-to-leading-order QCD calculations are compared to the measurements and provide a good description of the data, except for the case of the azimuthal opening angle.

Search for new phenomena in photon+jet events collected in proton–proton collisions at √s = 8 TeV with the ATLAS detector

This Letter describes a model-independent search for the production of new resonances in photon + jet events using 20 inverse fb of proton--proton LHC data recorded with the ATLAS detector at a centre-of-mass energy of s√ = 8 TeV. The photon + jet mass distribution is compared to a background model fit from data; no significant deviation from the background-only hypothesis is found. Limits are set at 95% credibility level on generic Gaussian-shaped signals and two benchmark phenomena beyond the Standard Model: non-thermal quantum black holes and excited quarks. Non-thermal quantum black holes are excluded below masses of 4.6 TeV and excited quarks are excluded below masses of 3.5 TeV.

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011.

Jet energy measurement with the ATLAS detector in proton-proton collisions at sqrt(s) = 7 TeV

The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of sqrt(s) = 7 TeV corresponding to an integrated luminosity of 38 inverse pb. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0.4 or R=0.6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pt > 20 GeV and pseudorapidities eta<4.5. The JES systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams. The JES uncertainty is less than 2.5% in the central calorimeter region (eta<0.8) for jets with 60 < pt < 800 GeV, and is maximally 14% for pt < 30 GeV in the most forward region 3.2 50 GeV after a dedicated correction for this effect. The JES is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pt, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pt jets recoiling against a high-pt jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, providing an improved jet energy resolution and a reduced flavour dependence of the jet response. The JES systematic uncertainty determined from a combination of in situ techniques are consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pt jets.