Measurement of the cosmogenic activation of germanium detectors in EDELWEISS-III

International audienceWe present a measurement of the cosmogenic activation in the germanium cryogenic detectors of the EDELWEISS III direct dark matter search experiment. The decay rates measured in detectors with different exposures to cosmic rays above ground are converted into production rates of different isotopes. The measured production rates in units of nuclei/kg/day are 82 $\pm$ 21 for $^3$H, 2.8 $\pm$ 0.6 for $^{49}$V, 4.6 $\pm$ 0.7 for $^{55}$Fe, and 106 $\pm$ 13 for $^{65}$Zn. These results are the most accurate for these isotopes. A lower limit on the production rate of $^{68}$Ge of 74 nuclei/kg/day is also presented. They are compared to model predictions present in literature and to estimates calculated with the ACTIVIA code

Signals induced by charge-trapping in EDELWEISS FID detectors: Analytical modeling and applications

The EDELWEISS-III direct dark matter search experiment uses cryogenic HP-Ge detectors Fully covered with Inter-Digitized electrodes (FID). They are operated at low fields (< 1 V/cm), and as a consequence charge-carrier trapping significantly affects both the ionization and heat energy measurements. This paper describes an analytical model of the signals induced by trapped charges in FID detectors based on the Shockley-Ramo theorem. It is used to demonstrate that veto electrodes, initially designed for the sole purpose of surface event rejection, can be used to provide a sensitivity to the depth of the energy deposits, characterize the trapping in the crystals, perform heat and ionization energy corrections and improve the ionization baseline resolutions. These procedures are applied successfully to actual data

Improved EDELWEISS-III sensitivity for low-mass WIMPs using a profile likelihood approach

We report on a dark matter search for a Weakly Interacting Massive Particle (WIMP) in the mass range mχ∈[4,30]GeV/c2 with the EDELWEISS-III experiment. A 2D profile likelihood analysis is performed on data from eight selected detectors with the lowest energy thresholds leading to a combined fiducial exposure of 496 kg-days. External backgrounds from γ- and β-radiation, recoils from 206Pb and neutrons as well as detector intrinsic backgrounds were modelled from data outside the region of interest and constrained in the analysis. The basic data selection and most of the background models are the same as those used in a previously published analysis based on boosted decision trees (BDT) [1]. For the likelihood approach applied in the analysis presented here, a larger signal efficiency and a subtraction of the expected background lead to a higher sensitivity, especially for the lowest WIMP masses probed. No statistically significant signal was found and upper limits on the spin-independent WIMP-nucleon scattering cross section can be set with a hypothesis test based on the profile likelihood test statistics. The 90 % C.L. exclusion limit set for WIMPs with mχ=4GeV/c2 is 1.6×10-39cm2, which is an improvement of a factor of seven with respect to the BDT-based analysis. For WIMP masses above 15GeV/c2 the exclusion limits found with both analyses are in good agreement

TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapy

Recent studies have suggested that activation of the EGFR pathway leads to malignant transformation only if the p53 protein is inactivated. Therefore, we evaluated the impact of TP53 mutations on cetuximab-based chemotherapy (CT) sensitivity in combination with KRAS mutations that have been associated with cetuximab resistance. KRAS and TP53 status were assessed in tumours from 64 metastatic colorectal cancer patients treated with cetuximab-based CT and correlated to clinical response using the Fisher's exact test. Times to progression (TTPs) according to gene status were calculated using the Kaplan–Meier method and compared with log-rank test. TP53 mutations were found in 41 patients and were significantly associated with controlled disease (CD), as defined as complete response, partial response or stable disease (P=0.037) and higher TTP (20 vs 12 weeks, P=0.004). Remarkably, in the subgroup of 46 patients without KRAS mutation, but not in patients with KRAS mutation, TP53 mutations were also associated with CD (P=0.008) and higher TTP (24 vs 12 weeks, P=0.0007). This study suggests that TP53 mutations are predictive of cetuximab sensitivity, particularly in patients without KRAS mutation, and that TP53 genotyping could have a clinical interest to select patients who should benefit from cetuximab-based CT

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Performance of the EDELWEISS-III experiment for direct dark matter searches

We present the results of measurements demonstrating the efficiency of the EDELWEISS-III array of cryogenic germanium detectors for direct dark matter searches. The experimental setup and the FID (Fully Inter-Digitized) detector array is described, as well as the efficiency of the double measurement of heat and ionization signals in background rejection. For the whole set of 24 FID detectors used for coincidence studies, the baseline resolutions for the fiducial ionization energy are mainly below 0.7 keV$_{ee}$ (FHWM) whereas the baseline resolutions for heat energies are mainly below 1.5 keV$_{ee}$ (FWHM). The response to nuclear recoils as well as the very good discrimination capability of the FID design has been measured with an AmBe source. The surface $\beta$- and $\alpha$-decay rejection power of $R_{\rm surf} < 4 \times 10^{-5}$ per $\alpha$ at 90% C.L. has been determined with a $^{210}$Pb source, the rejection of bulk $\gamma$-ray events has been demonstrated using $\gamma$-calibrations with $^{133}$Ba sources leading to a value of $R_{\gamma{\rm -mis-fid}} < 2.5 \times 10^{-6}$ at 90% C.L.. The current levels of natural radioactivity measured in the detector array are shown as the rate of single $\gamma$ background. The fiducial volume fraction of the FID detectors has been measured to a weighted average value of $(74.6 \pm 0.4)\%$ using the cosmogenic activation of the $^{65}$Zn and $^{68,71}$Ge isotopes. The stability and uniformity of the detector response is also discussed. The achieved resolutions, thresholds and background levels of the upgraded EDELWEISS-III detectors in their setup are thus well suited to the direct search of WIMP dark matter over a large mass range