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Abstract The specific activity of theβ β decay of³⁹39 Ar in atmospheric argon is measured using the DEAP-3600 detector. DEAP-3600, located 2 km underground at SNOLAB, uses a total of (3269 ± 24) kg of liquid argon distilled from the atmosphere to search for dark matter. This detector is well-suited to measure the decay of³⁹39 Ar owing to its very low background levels. This is achieved in two ways: it uses low background construction materials; and it uses pulse-shape discrimination to differentiate between nuclear recoils and electron recoils. With 167 live-days of data, the measured specific activity at the time of atmospheric extraction is (0.964 ± 0.001_(\\textrm{stat}{}{})stat ± 0.024_(\\textrm{sys}{}{})sys ) Bq/kg_(\\textrm{atmAr}{}{})atmAr , which is consistent with results from other experiments. A cross-check analysis using different event selection criteria and a different statistical method confirms the result.

The DEAP-3600 experiment is searching for WIMP dark matter with a 3.3 tonne single phase liquid argon (LAr) target, located 2.1 km underground at SNOLAB. The experimental signature of dark matter interactions is keV-scale \\(^40\\)Ar nuclear recoils (NR) producing 128 nm LAr scintillation photons observed by PMTs. The largest backgrounds in DEAP-3600 are electronic recoils (ER) induced by \\(\\) and \\(\\)-rays originating from internal and external radioactivity in the detector material. A background model of the ER interactions in DEAP-3600 was developed and is described in this work. The model is based on several components which are expected from radioisotopes in the LAr, from ex-situ material assay measurements, and from dedicated independent in-situ analyses. This prior information is used in a Bayesian fit of the ER components to a 247.2 d dataset to model the radioactivity in the surrounding detector materials. While excellent discrimination between ERs and NRs is reached with pulse shape discrimination, utilizing the large difference between fast and slow components of LAr scintillation light, detailed knowledge of the ER background and activity of detector components, sets valuable constraints on other key types of backgrounds in the detector: neutrons and alphas. In addition, the activity of \\(^42\\)Ar in LAr in DEAP-3600 is determined by measuring the daughter decay of \\(^42\\)K. This cosmogenically activated trace isotope is a relevant background at higher energies for other rare event searches using atmospheric argon e.g. DarkSide-20k, GERDA or LEGEND. The specific activity of \\(^42\\)Ar in the atmosphere is found to be \\(40.4 5.9\\) \\(\\)Bq/kg of argon.

DEAP-3600 is a single-phase liquid argon (LAr) direct-detection dark matter experiment, operating 2 km underground at SNOLAB (Sudbury, Canada). The detector consists of 3279 kg of LAr contained in a spherical acrylic vessel. This paper reports on the analysis of a 758 tonne day exposure taken over a period of 231 live-days during the first year of operation. No candidate signal events are observed in the WIMP-search region of interest, which results in the leading limit on the WIMP-nucleon spin-independent cross section on a LAr target of \\(3.910^-45\\) cm\\(^2\\) (\\(1.510^-44\\) cm\\(^2\\)) for a 100 GeV/c\\(^2\\) (1 TeV/c\\(^2\\)) WIMP mass at 90\\% C. L. In addition to a detailed background model, this analysis demonstrates the best pulse-shape discrimination in LAr at threshold, employs a Bayesian photoelectron-counting technique to improve the energy resolution and discrimination efficiency, and utilizes two position reconstruction algorithms based on PMT charge and photon arrival times.

This paper reports the first results of a direct dark matter search with the DEAP-3600 single-phase liquid argon (LAr) detector. The experiment was performed 2 km underground at SNOLAB (Sudbury, Canada) utilizing a large target mass, with the LAr target contained in a spherical acrylic vessel of 3600 kg capacity. The LAr is viewed by an array of PMTs, which would register scintillation light produced by rare nuclear recoil signals induced by dark matter particle scattering. An analysis of 4.44 live days (fiducial exposure of 9.87 tonne-days) of data taken with the nearly full detector during the initial filling phase demonstrates the detector performance and the best electronic recoil rejection using pulse-shape discrimination in argon, with leakage \\(<1.2 10^-7\\) (90% C.L.) between 16 and 33 keV\\(_ee\\). No candidate signal events are observed, which results in the leading limit on WIMP-nucleon spin-independent cross section on argon, \\(<1.2 10^-44\\) cm\\(^2\\) for a 100 GeV/c\\(^2\\) WIMP mass (90% C.L.).

The Dark matter Experiment using Argon Pulse-shape discrimination (DEAP) has been designed for a direct detection search for particle dark matter using a single-phase liquid argon target. The projected cross section sensitivity for DEAP-3600 to the spin-independent scattering of Weakly Interacting Massive Particles (WIMPs) on nucleons is \\(10^-46~cm^2\\) for a 100 GeV/\\(c^2\\) WIMP mass with a fiducial exposure of 3 tonne-years. This paper describes the physical properties and construction of the DEAP-3600 detector.

The catechol-O-methyl transferase ( COMT) 158Val/Met variant has been suggested to play a role in COMT function. Epigenetic regulation of COMT may further influence the prevalence of metabolic syndrome in these patient populations. This study examined the correlation between COMT promoter methylation and metabolic syndrome in schizophrenia patients receiving atypical antipsychotic (AAP) therapy. DNA was extracted from peripheral blood samples of schizophrenia subjects screened for metabolic syndrome. Pyrosequencing was used to analyze two methylation sites of the soluble COMT (COMT- s) promoter region. Associations between AAP use, lifestyle variables, metabolic syndrome and COMT genotype with peak methylation values were analyzed. Data are reported in 85 subjects. Methylation on CpG site 1 had a mean of 79.08% (±4.71) and it was 12.43% (±1.19) on site 2. COMT genotype proved to be an indicator of COMT methylation status on site 1 (F (2, 84) =5.78, P =0.0044) and site 2 (F (2, 84) ,=3.79, P =0.027). A significant negative correlation between physical activity and COMT promoter region methylation was found in Val/Val homozygous patients (site 1: P =0.013 and site 2: P =0.019). Those homozygous for Met/Met showed a positive correlation between promoter site methylation and physical activity (site 1: P =0.027, site 2: P =0.005), and between CpG site methylation and metabolic syndrome (site 1: P =0.002; site 2: P =0.001). The results of this study suggest that COMT promoter region methylation is largely influenced by COMT genotype and that physical activity plays a significant role in epigenetic modulation of COMT .

Understanding mechanisms controlling fluid injection-triggered seismicity is key in defining strategies to ameliorate it. Recent triggered events (e.g. Pohang, Mw 5.5) have exceeded predictions of average energy release by a factor of >1000x, necessitating robust methodologies to both define critical antecedent conditions and to thereby constrain anticipated event size. We define maximum event magnitudes resulting from triggering as a function of pre-existing critical stresses and fluid injection volume. Fluid injection experiments on prestressed laboratory faults confirm these estimates of triggered moment magnitudes for varied boundary conditions and injection rates. In addition, observed ratios of shear slip to dilation rates on individual faults signal triggering and may serve as a measurable proxy for impending rupture. This new framework provides a robust method of constraining maximum event size for preloaded faults and unifies prior laboratory and field observations that span sixteen decades in injection volume and four decades in length scale. Recently triggered seismic events such as the Pohang earthquake have exceeded predictions of average energy releases by a factor of 1000. A new framework is proposed to define maximum event magnitudes as a function of pre-existing critical stresses and fluid injection volume.

Bone structure is an integral determinant of bone strength. The availability of high resolution peripheral quantitative computed tomography (HR-pQCT) has made it possible to measure three-dimensional bone microarchitecture and volumetric bone mineral density in vivo, with accuracy previously unachievable and with relatively low-dose radiation. Recent studies using this novel imaging tool have increased our understanding of age-related changes and sex differences in bone microarchitecture, as well as the effect of different pharmacological therapies. One advantage of this novel tool is the use of finite element analysis modelling to non-invasively estimate bone strength and predict fractures using reconstructed three-dimensional images. In this paper, we describe the strengths and limitations of HR-pQCT and review the clinical studies using this tool.

SummaryDairy protein but not plant protein was associated with bone strength of the radius and tibia in older men. These results are consistent with previous results in women and support similar findings related to fracture outcomes. Bone strength differences were largely due to thickness and area of the bone cortex.IntroductionOur objective was to determine the association of protein intake by source (dairy, non-dairy animal, plant) with bone strength and bone microarchitecture among older men.MethodsWe used data from 1016 men (mean 84.3 years) who attended the Year 14 exam of the Osteoporotic Fractures in Men (MrOS) study, completed a food frequency questionnaire (500–5000 kcal/day), were not taking androgen or androgen agonists, and had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia. Protein was expressed as percentage of total energy intake (TEI); mean ± SD for TEI = 1548 ± 607 kcal/day and for total protein = 16.2 ± 2.9%TEI. We used linear regression with standardized HR-pQCT parameters as dependent variables and adjusted for age, limb length, center, education, race/ethnicity, marital status, smoking, alcohol intake, physical activity level, corticosteroids use, supplement use (calcium and vitamin D), and osteoporosis medications.ResultsHigher dairy protein intake was associated with higher estimated failure load at the distal radius and distal tibia [radius effect size = 0.17 (95% CI 0.07, 0.27), tibia effect size = 0.13 (95% CI 0.03, 0.23)], while higher non-dairy animal protein was associated with higher failure load at only the distal radius. Plant protein intake was not associated with failure load at any site.ConclusionThe association between protein intake and bone strength varied by source of protein. These results support a link between dairy protein intake and skeletal health, but an intervention study is needed to evaluate causality.

Glioblastoma is the most common and aggressive form of intrinsic brain tumor. Transforming growth factor (TGF)-β represents a central mediator of the malignant phenotype of these tumors by promoting invasiveness and angiogenesis, maintaining tumor cell stemness and inducing profound immunosuppression. Integrins, which are highly expressed in glioma cells, interact with the TGF-β pathway. Furthermore, a link has been described between activity of the transcription factor aryl hydrocarbon receptor (AhR) and TGF-β expression. Here we demonstrate that integrin inhibition, using αv, β3 or β5 neutralizing antibodies, RNA interference-mediated integrin gene silencing or pharmacological inhibition by the cyclic RGD peptide EMD 121974 (cilengitide) or the non-peptidic molecule GLPG0187, inhibits AhR activity. These effects are independent of cell detachment or cell density. While AhR mRNA expression was not affected by integrin inhibition, AhR total and nuclear protein levels were reduced, suggesting that integrin inhibition-mediated regulation of AhR may occur at a post-transcriptional level. AhR-null astrocytes, AhR-null hepatocytes or glioblastoma cells with a transiently silenced AhR gene showed reduced sensitivity to integrin inhibition-mediated alterations in TGF-β signaling, indicating that AhR mediates integrin control of the TGF-β pathway. Accordingly, there was a significant correlation of αv integrin levels with nuclear AhR and pSmad2 levels as determined by immunohistochemistry in human glioblastoma in vivo . In summary, this study identifies a signaling network comprising integrins, AhR and TGF-β and validates integrin inhibition as a promising strategy not only to inhibit angiogenesis, but also to block AhR- and TGF-β-controlled features of malignancy in human glioblastoma.