Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

The rapid atmospheric monitoring system of the Pierre Auger Observatory

The Pierre Auger Observatory is a facility built to detect air showers produced by cosmic rays above 10(17) eV. During clear nights with a low illuminated moon fraction, the UV fluorescence light produced by air showers is recorded by optical telescopes at the Observatory. To correct the observations for variations in atmospheric conditions, atmospheric monitoring is performed at regular intervals ranging from several minutes (for cloud identification) to several hours (for aerosol conditions) to several days (for vertical profiles of temperature, pressure, and humidity). In 2009, the monitoring program was upgraded to allow for additional targeted measurements of atmospheric conditions shortly after the detection of air showers of special interest, e. g., showers produced by very high-energy cosmic rays or showers with atypical longitudinal profiles. The former events are of particular importance for the determination of the energy scale of the Observatory, and the latter are characteristic of unusual air shower physics or exotic primary particle types. The purpose of targeted (or 'rapid') monitoring is to improve the resolution of the atmospheric measurements for such events. In this paper, we report on the implementation of the rapid monitoring program and its current status. The rapid monitoring data have been analyzed and applied to the reconstruction of air showers of high interest, and indicate that the air fluorescence measurements affected by clouds and aerosols are effectively corrected using measurements from the regular atmospheric monitoring program. We find that the rapid monitoring program has potential for supporting dedicated physics analyses beyond the standard event reconstruction

Techniques for measuring aerosol attenuation using the Central Laser Facility at the Pierre Auger Observatory

The Pierre Auger Observatory in Malargüe, Argentina, is designed to study the properties of ultra-high energy cosmic rays with energies above 10(18) eV. It is a hybrid facility that employs a Fluorescence Detector to perform nearly calorimetric measurements of Extensive Air Shower energies. To obtain reliable calorimetric information from the FD, the atmospheric conditions at the observatory need to be continuously monitored during data acquisition. In particular, light attenuation due to aerosols is an important atmospheric correction. The aerosol concentration is highly variable, so that the aerosol attenuation needs to be evaluated hourly. We use light from the Central Laser Facility, located near the center of the observatory site, having an optical signature comparable to that of the highest energy showers detected by the FD. This paper presents two procedures developed to retrieve the aerosol attenuation of fluorescence light from CLF laser shots. Cross checks between the two methods demonstrate that results from both analyses are compatible, and that the uncertainties are well understood. The measurements of the aerosol attenuation provided by the two procedures are currently used at the Pierre Auger Observatory to reconstruct air shower data

Ultrahigh energy neutrinos at the Pierre Auger observatory

The observation of ultrahigh energy neutrinos (UHEνs) has become a priority in experimental astroparticle physics. UHEνs can be detected with a variety of techniques. In particular, neutrinos can interact in the atmosphere (downward-going ν) or in the Earth crust (Earth-skimming ν), producing air showers that can be observed with arrays of detectors at the ground. With the surface detector array of the Pierre Auger Observatory we can detect these types of cascades. The distinguishing signature for neutrino events is the presence of very inclined showers produced close to the ground (i.e., after having traversed a large amount of atmosphere). In this work we review the procedure and criteria established to search for UHEνs in the data collected with the ground array of the Pierre Auger Observatory. This includes Earth-skimming as well as downward-going neutrinos. No neutrino candidates have been found, which allows us to place competitive limits to the diffuse flux of UHEνs in the EeV range and above.P. Abreu ... K. B. Barber ... J. A. Bellido ... R. W. Clay ... M. J. Cooper ... B. R. Dawson ... T. A. Harrison ... A. E. Herve ... V. C. Holmes ... J. Sorokin ... P. Wahrlich ... B. J. Whelan ... et al

Cu deficiency in multi stage co evaporated Cu In,Ga Se2 for solar cells applications Microstructure and Ga in depth alloying

The objective of this work is to study the influence of the maximum Cu content during the deposition of Cu In,Ga Se2 CIGSe by multi stage co evaporation on the phases present in the final film, the film structure and the electrical properties of resulting solar cell devices. The variation of the composition is controlled by the Cu content in stage 2 of the deposition process. The different phases are identified by Raman spectroscopy. The in depth Ga gradient distribution is investigated by in depth resolved Raman scattering and secondary neutral mass spectroscopy. The morphology of the devices is studied by scanning electron microscopy. Efficiencies of 9.2 are obtained for ordered vacancy compound based solar cells with a Cu In Ga 0.35, showing the system s flexibility. This work supports the current growth model a small amount of Cu excess during the absorber process is required to obtain a quality microstructure and high performances device

Raman scattering analysis of Cu poor Cu In,Ga Se2 cells fabricated on polyimide substrates Effect of Na content on microstructure and phase structure

This work reports the Raman scattering surface and in depth resolved analysis of Cu poor Cu In,Ga Se2 CIGS grown on polyimide substrates. In order to study the effect of Na on the formation and microstructure of the CIGS and the corresponding Cu poor ordered vacancy compound OVC phases, a NaF precursor layer with different thicknesses was deposited on the Mo coated substrates before growing of the samples. The Raman spectroscopy data are correlated with the analysis of the samples by Auger electron spectroscopy and scanning electron microscopy. These data corroborate the significant role of Na on the inhibition of Ga In interdiffusion and on the formation of the MoSe2 interfacial phase at the back region of the layers. Presence of Na also leads to an enhancement in the formation of the chalcopyrite CIGS phase and a decrease in the occurrence of the dominant OVC phase at the surface region. This study confirms the strong dependence of the microstructure and phase distribution in CIGS absorber layers on the Na available during their growt

Paraoxonase-1 status in patients with hereditary hemochromatosis.

Hereditary hemochromatosis (HH) is characterized by accumulation of iron, oxidative stress, inflammation, and fibrogenesis in liver tissue. In this setting, research on the protection afforded by intracellular antioxidants is of clinical relevance. Paraoxonase-1 (PON1) is an enzyme that degrades lipid peroxides. This study investigates the alterations in serum PON1 status, PON1 gene polymorphisms, and PON1 hepatic expression in patients with HH. We performed a case-control study in 77 patients with HH (80.5% men, 22-70 years of age) and 408 healthy individuals (43.1% men, 26-74 years of age). Serum PON1 activities against different substrates and PON1192 and PON155 polymorphisms were analyzed. PON1 protein expression was investigated in 20 liver biopsies. HH patients had significantly lower serum PON1 activity, which was inversely correlated with ferritin (marker of iron stores) and serum 8-isoprostane concentrations (index of oxidative stress). PON1 protein expression in liver tissue was higher in patients and showed stronger staining in hepatocytes surrounding the areas of inflammation. Our study provides preliminary evidence that PON1 may play a role in protecting against iron-induced oxidative stress in hereditary hemochromatosis