Caloric dose-responsive genes in blood cells differentiate the metabolic status of obese men.

We have investigated the postprandial transcriptional response of blood cells to increasing caloric doses of a meal challenge to test whether the dynamic response of the human organism to the ingestion of food is dependent on metabolic health. The randomized crossover study included seven normal weight and seven obese men consuming three doses (500/1000/1500 kcal) of a high-fat meal. The blood cell transcriptome was measured before and 2, 4, and 6 h after meal ingestion (168 samples). We applied univariate and multivariate statistics to investigate differentially expressed genes in both study groups. We identified 624 probe sets that were up- or down-regulated after the caloric challenge in a dose-dependent manner. These transcripts were most responsive to the 1500 kcal challenge in the obese group and were associated with postprandial insulin and oxidative phosphorylation. Furthermore, the data revealed a separation of the obese group into individuals whose response was close to the normal weight group and individuals with a transcriptional response indicative of a loss of metabolic flexibility. The molecular signature provided by the postprandial transcriptomic response of blood cells to increasing caloric doses of a high-fat meal challenge may represent a sensitive way to evaluate the qualitative impact of food on human health

Metabolic Footprinting of Fermented Milk Consumption in Serum of Healthy Men.

Fermentation is a widely used method of natural food preservation that has consequences on the nutritional value of the transformed food. Fermented dairy products are increasingly investigated in view of their ability to exert health benefits beyond their nutritional qualities. To explore the mechanisms underpinning the health benefits of fermented dairy intake, the present study followed the effects of milk fermentation, from changes in the product metabolome to consequences on the human serum metabolome after its ingestion. A randomized crossover study design was conducted in 14 healthy men [mean age: 24.6 y; mean body mass index (in kg/m2): 21.8]. At the beginning of each test phase, serum samples were taken 6 h postprandially after the ingestion of 800 g of a nonfermented milk or a probiotic yogurt. During the 2-wk test phases, subjects consumed 400 g of the assigned test product daily (200 g, 2 times/d). Serum samples were taken from fasting participants at the end of each test phase. The serum metabolome was assessed through the use of LC-MS-based untargeted metabolomics. Postprandial serum metabolomes after milk or yogurt intake could be differentiated [orthogonal projections to latent structures discriminant analysis (OPLS-DA) Q2 = 0.74]. Yogurt intake was characterized by higher concentrations of 7 free amino acids (including proline, P = 0.03), reduced concentrations of 5 bile acids (including glycocholic acid, P = 0.04), and modulation of 4 indole derivative compounds (including indole lactic acid, P = 0.01). Fasting serum samples after 2 wk of daily intake of milk or yogurt could also be differentiated based on their metabolic profiles (OPLS-DA Q2 = 0.56) and were discussed in light of the postprandial results. Metabolic pathways related to amino acids, indole derivatives, and bile acids were modulated in healthy men by the intake of yogurt. Further investigation to explore novel health effects of fermented dairy products is warranted.This trial was registered at clinicaltrials.gov as NCT02230345

Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal

Lowering the radioactivity of the photomultiplier tubes for the XENON1T dark matter experiment

The low-background, VUV-sensitive 3-inch diameter photomultiplier tube R11410 has been developed by Hamamatsu for dark matter direct detection experiments using liquid xenon as the target material. We present the results from the joint effort between the XENON collaboration and the Hamamatsu company to produce a highly radio-pure photosensor (version R11410-21) for the XENON1T dark matter experiment. After introducing the photosensor and its components, we show the methods and results of the radioactive contamination measurements of the individual materials employed in the photomultiplier production. We then discuss the adopted strategies to reduce the radioactivity of the various PMT versions. Finally, we detail the results from screening 216 tubes with ultra-low background germanium detectors, as well as their implications for the expected electronic and nuclear recoil background of the XENON1T experiment.Comment: 10 pages, 5 figure

Search for Event Rate Modulation in XENON100 Electronic Recoil Data

We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an un-binned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1 sigma for all periods suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8 sigma, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of WIMPs to electrons is excluded at 4.8 sigma.Comment: 6 pages, 4 figure

Search for Two-Neutrino Double Electron Capture of 124^{124}Xe with XENON100

Two-neutrino double electron capture is a rare nuclear decay where two electrons are simultaneously captured from the atomic shell. For $^{124}$Xe this process has not yet been observed and its detection would provide a new reference for nuclear matrix element calculations. We have conducted a search for two-neutrino double electron capture from the K-shell of $^{124}$Xe using 7636 kg$\cdot$d of data from the XENON100 dark matter detector. Using a Bayesian analysis we observed no significant excess above background, leading to a lower 90 % credibility limit on the half-life $T_{1/2}>6.5\times10^{20}$ yr. We also evaluated the sensitivity of the XENON1T experiment, which is currently being commissioned, and find a sensitivity of $T_{1/2}>6.1\times10^{22}$ yr after an exposure of 2 t$\cdot$yr.Comment: 6 pages, 4 figure

Removing krypton from xenon by cryogenic distillation to the ppq level

The XENON1T experiment aims for the direct detection of dark matter in a cryostat filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the $\beta$-emitter $^{85}$Kr which is an intrinsic contamination of the xenon. For the XENON1T experiment a concentration of natural krypton in xenon $\rm{^{nat}}$Kr/Xe < 200 ppq (parts per quadrillion, 1 ppq = 10$^{-15}$ mol/mol) is required. In this work, the design of a novel cryogenic distillation column using the common McCabe-Thiele approach is described. The system demonstrated a krypton reduction factor of 6.4$\cdot$10$^5$ with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of $\rm{^{nat}}$Kr/Xe < 26 ppq is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN

Search for Two-Neutrino Double Electron Capture of ¹²⁴Xe with XENON100

Two-neutrino double electron capture is a rare nuclear decay where two electrons are simultaneously captured from the atomic shell. For $^{124}$Xe this process has not yet been observed and its detection would provide a new reference for nuclear matrix element calculations. We have conducted a search for two-neutrino double electron capture from the K-shell of $^{124}$Xe using 7636 kg$\cdot$d of data from the XENON100 dark matter detector. Using a Bayesian analysis we observed no significant excess above background, leading to a lower 90 % credibility limit on the half-life $T_{1/2}>6.5\times10^{20}$ yr. We also evaluated the sensitivity of the XENON1T experiment, which is currently being commissioned, and find a sensitivity of $T_{1/2}>6.1\times10^{22}$ yr after an exposure of 2 t$\cdot$yr

Physics reach of the XENON1T dark matter experiment

The XENON1T experiment is currently in the commissioning phase at theLaboratori Nazionali del Gran Sasso, Italy. In this article we study theexperiment's expected sensitivity to the spin-independent WIMP-nucleoninteraction cross section, based on Monte Carlo predictions of the electronicand nuclear recoil backgrounds. The total electronic recoil background in $1$ tonne fiducial volume and ($1$,$12$) keV electronic recoil equivalent energy region, before applying anyselection to discriminate between electronic and nuclear recoils, is $(1.80 \pm0.15) \cdot 10^{-4}$ ($\rm{kg} \cdot day \cdot keV)^{-1}$, mainly due to thedecay of $^{222}\rm{Rn}$ daughters inside the xenon target. The nuclear recoilbackground in the corresponding nuclear recoil equivalent energy region ($4$,$50$) keV, is composed of $(0.6 \pm 0.1)$ ($\rm{t} \cdot y)^{-1}$ fromradiogenic neutrons, $(1.8 \pm 0.3) \cdot 10^{-2}$ ($\rm{t} \cdot y)^{-1}$ fromcoherent scattering of neutrinos, and less than $0.01$ ($\rm{t} \cdot y)^{-1}$from muon-induced neutrons. The sensitivity of XENON1T is calculated with the Profile Likelihood Ratiomethod, after converting the deposited energy of electronic and nuclear recoilsinto the scintillation and ionization signals seen in the detector. We takeinto account the systematic uncertainties on the photon and electron emissionmodel, and on the estimation of the backgrounds, treated as nuisanceparameters. The main contribution comes from the relative scintillationefficiency $\mathcal{L}_\mathrm{eff}$, which affects both the signal from WIMPsand the nuclear recoil backgrounds. After a $2$ y measurement in $1$ t fiducialvolume, the sensitivity reaches a minimum cross section of $1.6 \cdot 10^{-47}$cm$^2$ at m$_\chi$=$50$ GeV/$c^2$

Online 222^{222}Rn removal by cryogenic distillation in the XENON100 experiment

We describe the purification of xenon from traces of the radioactive noble gas radon using a cryogenic distillation column. The distillation column was integrated into the gas purification loop of the XENON100 detector for online radon removal. This enabled us to significantly reduce the constant ²²²Rn background originating from radon emanation. After inserting an auxiliary ²²²Rn emanation source in the gas loop, we determined a radon reduction factor of R>27 (95% C.L.) for the distillation column by monitoring the ²²²Rn activity concentration inside the XENON100 detector