A Light Calibration System for the ProtoDUNE-DP Detector

A LED-based fiber calibration system for the ProtoDUNE-Dual Phase (DP) photon detection system (PDS) has been designed and validated. ProtoDUNE-DP is a 6x6x6 m3 liquid argon time-projection-chamber currently being installed at the Neutrino Platform at CERN. The PDS is based on 36 8-inch photomultiplier tubes (PMTs) and will allow triggering on cosmic rays. The system serves as prototype for the PDS of the final DUNE DP far detector in which the PDS also has the function to allow the 3D event reconstruction on non-beam physics. For this purpose an equalized PMT response is desirable to allow using the same threshold definition for all PMT groups, simplifying the determination of the trigger efficiency. The light calibration system described in this paper is developed to provide this and to monitor the PMT performance in-situ.Comment: 15 pages, 5 figure

Lipid phenotype and heritage pattern in families with genetic hypercholesterolemia not related to LDLR, APOB, PCSK9, or APOE

Background: A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied. Objectives: We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH). Methods: The study included probands with a clinical diagnosis of FH and their families attending 2 lipid clinics in Spain. Inclusion criteria for probands were LDLc >95th percentile, triglycerides 90th percentile, >5 points in the Dutch Lipid Clinic Network criteria score, and absence of mutations in LDLR, APOB, PCSK9 or APOE. Eleven FH families with a LDLR mutation were also examined for comparison. Results: We analyzed 49 non-FH-GH probands and 277 first-and second-degree relatives. LDLc was >90th percentile in 37.8% of blood relatives, at concentrations similar to those of probands. LDLc had a normal distribution in non-FH-GH families, in contrast with a bimodal distribution in FH families. When a dominant model was tested, family-based association tests gave much lower heritability values for total cholesterol and LDLc in non-FH-GH (0.39 and 0.32, respectively) than in FH (0.78 and 0.61, respectively). Conclusions: Non-FH-GH families have a milder lipid phenotype than genetically defined FH. The heritage pattern of LDLc in non-FH-GH does not fit with a monogenic disorder. Our findings support the concept that most non-FH-GHs are polygenic hypercholesterolemias

CATÁLOGO DE LOS BRIÓFITOS DE LA PROVINCIA DE MURCIA (SURESTE DE ESPAÑA)

A check-list of the bryophytes of Murcia province is provided. Bryophyte diversity in Murcia consists of 200 taxa (74 genera) of mosses and 32 taxa (20 genera) of liverworts. Pseudocrossidium obtusulum is reported as new to the Iberian Peninsula. A total of 30 taxa are new record from Murcia: Acaulon casasianum, Astomum levieri, Bryoerythrophyllum recurvirostrum, Crossidium laevipilum, Entosthodon convexus, Grimmia dissimulata, Gymnostomum lanceolatum, Hedwigia ciliata, Orthotrichum affine, O. pumilum, O. scanicum, O. schimperi, O. striatum, O. tenellum, O. tortidontium, O. vittii, Philonotis fontana, Pleuridium acuminatum, Pohlia cruda, Pterygoneurum subsessile, Rhynchostegiella tenella, Schistidium crassipilum, Schistidium singarense, Syntrichia virescens, Tortula canescens, T. mucronifolia, Weissia brachycarpa, W. condensa var. armata, Athalamia hyalina, and Jungermannia atrovirens. Thirty eight taxa (33 mosses and 5 liverworts) are excluded from the checklist or represent doubtful reports for Murcia.Se realiza un catalogo de los briofitos de la provincia de Murcia. La diversidad briofitica de Murcia se estima en 200 taxones (74 generos) de musgos y 32 taxones de hepaticas (20 generos). Pseudocrossidium obtusulum se cita por primera vez en la Peninsula Iberica. Un total de 30 taxones son novedades para la provincia de Murcia: Acaulon casasianum, Astomum levieri, Bryoerythrophyllum recurvirostrum, Crossidium laevipilum, Entosthodon convexus, Grimmia dissimulata, Gymnostomum lanceolatum, Hedwigia ciliata, Orthotrichum affine, O. pumilum, O. scanicum, O. schimperi, O. striatum, O. tenellum, O. tortidontium, O. vittii, Philonotis fontana, Pleuridium acuminatum, Pohlia cruda, Pterygoneurum subsessile, Rhynchostegiella tenella, Schistidium crassipilum, Schistidium singarense, Syntrichia virescens, Tortula canescens, T. mucronifolia, Weissia brachycarpa, W. condensa var. armata, Athalamia hyalina y Jungermannia atrovirens. Treinta y ocho taxones (33 musgos y 5 hepaticas) se han excluido del catalogo de la provincia o se citan como dudosos

Epigenetics modifications and Subclinical Atherosclerosis in Obstructive Sleep Apnea: The EPIOSA study.

Background Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular morbidity and mortality. Epidemiological and animal models studies generate hypotheses for innovative strategies in OSA management by interferig intermediates mechanisms associated with cardiovascular complications. We have thus initiated the Epigenetics modification in Obstructive Sleep Apnea (EPIOSA) study (ClinicalTrials.gov identifier: NCT02131610). Methods/design EPIOSA is a prospective cohort study aiming to recruit 350 participants of caucasian ethnicity and free of other chronic or inflammatory diseases: 300 patients with prevalent OSA and 50 non-OSA subjects. All of them will be follow-up for at least 5 years. Recruitment and study visits are performed in single University-based sleep clinic using standard operating procedures. At baseline and at each one year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized questionnaire and physical examination to determine incident comorbidities and health resources utilization, with a primary focus on cardiovascular events. Confirmatory outcomes information is requested from patient records and the regional Department of Health Services. Every year, OSA status will be assessed by full sleep study and blood samples will be obtained for immediate standard biochemistry, hematology, inflammatory cytokines and cytometry analysis. For biobanking, aliquots of serum, plasma, urine, mRNA and DNA are also obtained. Bilateral carotid echography will be performed to assess subclinical atherosclerosis and atherosclerosis progression. OSA patients are treated according with national guidelines. Discussion EPIOSA will enable the prospective evaluation of inflammatory and epigenetics mechanism involved in cardiovascular complication of treated and non-treated patients with OSA compared with non OSA subjects

A genetic variant in the LDLR promoter is responsible for part of the LDL-cholesterol variability in primary hypercholesterolemia

BACKGROUND: GWAS have consistently revealed that LDLR locus variability influences LDL-cholesterol in general population. Severe LDLR mutations are responsible for familial hypercholesterolemia (FH). However, most primary hypercholesterolemias are polygenic diseases. Although Cis-regulatory regions might be the cause of LDL-cholesterol variability; an extensive analysis of the LDLR distal promoter has not yet been performed. We hypothesized that genetic variants in this region are responsible for the LDLR association with LDL-cholesterol found in GWAS. METHODS: Four-hundred seventy-seven unrelated subjects with polygenic hypercholesterolemia (PH) and without causative FH-mutations and 525 normolipemic subjects were selected. A 3103 pb from LDLR (-625 to +2468) was sequenced in 125 subjects with PH. All subjects were genotyped for 4 SNPs (rs17242346, rs17242739, rs17248720 and rs17249120) predicted to be potentially involved in transcription regulation by in silico analysis. EMSA and luciferase assays were carried out for the rs17248720 variant. Multivariable linear regression analysis using LDL-cholesterol levels as the dependent variable were done in order to find out the variables that were independently associated with LDL-cholesterol. RESULTS: The sequencing of the 125 PH subjects did not show variants with minor allele frequency ≥ 10%. The T-allele from g.3131C > T (rs17248720) had frequencies of 9% (PH) and 16.4% (normolipemic), p < 0.00001. Studies of this variant with EMSA and luciferase assays showed a higher affinity for transcription factors and an increase of 2.5 times in LDLR transcriptional activity (T-allele vs C-allele). At multivariate analysis, this polymorphism with the lipoprotein(a) and age explained ≈ 10% of LDL-cholesterol variability. CONCLUSION: Our results suggest that the T-allele at the g.3131 T > C SNP is associated with LDL-cholesterol levels, and explains part of the LDL-cholesterol variability. As a plausible cause, the T-allele produces an increase in LDLR transcriptional activity and lower LDL-cholesterol levels

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal