Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

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

Depth Of Maximum Of Air-shower Profiles At The Pierre Auger Observatory. I. Measurements At Energies Above 1017.8ev

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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

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

Ultrahigh energy neutrinos at the pierre auger observatory

The observation of ultrahigh energy neutrinos (UHEs) has become a priority in experimental astroparticle physics. UHEs can be detected with a variety of techniques. In particular, neutrinos can interact in the atmosphere (downward-going ) or in the Earth crust (Earth-skimming ), 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 UHEs 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 UHEs in the EeV range and above

Volume I. Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

Description of Atmospheric Conditions at the Pierre Auger Observatory using the Global Data Assimilation System (GDAS)

Atmospheric conditions at the site of a cosmic ray observatory must be known for reconstructing observed extensive air showers. The Global Data Assimilation System (GDAS) is a global atmospheric model predicated on meteorological measurements and numerical weather predictions. GDAS provides altitude-dependent profiles of the main state variables of the atmosphere like temperature, pressure, and humidity. The original data and their application to the air shower reconstruction of the Pierre Auger Observatory are described. By comparisons with radiosonde and weather station measurements obtained on-site in Malarg\"ue and averaged monthly models, the utility of the GDAS data is shown

Measurement of the longitudinal diffusion of ionization electrons in the MicroBooNE detector

Abstract: Accurate knowledge of electron transport properties is vital to understanding the information provided by liquid argon time projection chambers (LArTPCs). Ionization electron drift-lifetime, local electric field distortions caused by positive ion accumulation, and electron diffusion can all significantly impact the measured signal waveforms. This paper presents a measurement of the effective longitudinal electron diffusion coefficient, DL, in MicroBooNE at the nominal electric field strength of 273.9 V/cm. Historically, this measurement has been made in LArTPC prototype detectors. This represents the first measurement in a large-scale (85 tonne active volume) LArTPC operating in a neutrino beam. This is the largest dataset ever used for this measurement. Using a sample of ∼70,000 through-going cosmic ray muon tracks tagged with MicroBooNE's cosmic ray tagger system, we measure DL = 3.74+0.28 -0.29 cm2/s

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