Members of the EGF family of growth factors play critical roles during normal and neoplastic breast development. EGF family member HRGalpha is the only HRG1 isoform expressed in the mouse mammary ...gland and our previous experiments suggest that HRG1 has a unique role in mammary development. To determine the function of HRGalpha activity during mouse mammary gland development, we generated a HRGalpha-deficient mouse strain. Unlike mice with HRG1 or isoform specific HRGbeta gene deletions, HRGalpha-null mice survive to adulthood. HRGalpha-deficient mice display pronounced defects in mammary gland lobuloalveolar development at 17 days of pregnancy and 3 days post-partum. Terminal and lateral ductal alveoli were condensed and alveolar outgrowth during pregnancy was severely impaired. A dramatic reduction in beta-casein expression accompanied defective alveolar development in the HRGalpha-null mice, as determined by in situ hybridization and Northern blot analysis of HRGalpha-deficient mammary glands at 3 days post-partum. Expression of the milk-protein genes WAP and alpha-lactalbumin was not adversely affected. In situ incorporation of BrdU demonstrated that epithelial proliferation was significantly curtailed in mammary glands of HRGalpha-deficient mice at 17 days post-coitus and 3 days post-partum. These results demonstrate that HRGalpha is an important mammary gland mitogen regulating alveolar development and lactogenesis.
Members of the EGF family of growth factors play critical roles during normal and neoplastic breast development. EGF family member HRGalpha is the only HRG1 isoform expressed in the mouse mammary ...gland and our previous experiments suggest that HRG1 has a unique role in mammary development. To determine the function of HRGalpha activity during mouse mammary gland development, we generated a HRGalpha-deficient mouse strain. Unlike mice with HRG1 or isoform specific HRGbeta gene deletions, HRGalpha-null mice survive to adulthood. HRGalpha-deficient mice display pronounced defects in mammary gland lobuloalveolar development at 17 days of pregnancy and 3 days post-partum. Terminal and lateral ductal alveoli were condensed and alveolar outgrowth during pregnancy was severely impaired. A dramatic reduction in beta-casein expression accompanied defective alveolar development in the HRGalpha-null mice, as determined by in situ hybridization and Northern blot analysis of HRGalpha-deficient mammary glands at 3 days post-partum. Expression of the milk-protein genes WAP and alpha-lactalbumin was not adversely affected. In situ incorporation of BrdU demonstrated that epithelial proliferation was significantly curtailed in mammary glands of HRGalpha-deficient mice at 17 days post-coitus and 3 days post-partum. These results demonstrate that HRGalpha is an important mammary gland mitogen regulating alveolar development and lactogenesis.
The DarkSide-50 direct-detection dark matter experiment is a dual-phase argon time projection chamber operating at Laboratori Nazionali del Gran Sasso. This paper reports on the blind analysis of a ...(16,660+-270) kg d exposure using a target of low-radioactivity argon extracted from underground sources. We find no events in the dark matter selection box and set a 90% C.L. upper limit on the dark matter-nucleon spin-independent cross section of 1.14E-44 cm^2 (3.78E-44 cm^2, 3.43E-43 cm^2) for a WIMP mass of 100 GeV/c^2 (1 TeV/c^2, 10 TeV/c^2).
We present new constraints on sub-GeV dark matter particles scattering off electrons in argon based on an analysis of ionization signal data from the DarkSide-50 detector.
We present the results of a search for dark matter WIMPs in the mass range below 20 GeV/c^2 using a target of low-radioactivity argon. The data were obtained using the DarkSide-50 apparatus at ...Laboratori Nazionali del Gran Sasso (LNGS). The analysis is based on the ionization signal, for which the DarkSide-50 time projection chamber is fully efficient at 0.1 keVee. The observed rate in the detector at 0.5 keVee is about 1.5 events/keVee/kg/day and is almost entirely accounted for by known background sources. We obtain a 90% C.L. exclusion limit above 1.8 GeV/c^2 for the spin-independent cross section of dark matter WIMPs on nucleons, extending the exclusion region for dark matter below previous limits in the range 1.8-6 GeV/c^2.
We report the measurement of the longitudinal diffusion constant in liquid argon with the DarkSide-50 dual-phase time projection chamber. The measurement is performed at drift electric fields of 100 ...V/cm, 150 V/cm, and 200 V/cm using high statistics \(^{39}\)Ar decays from atmospheric argon. We derive an expression to describe the pulse shape of the electroluminescence signal (S2) in dual-phase TPCs. The derived S2 pulse shape is fit to events from the uppermost portion of the TPC in order to characterize the radial dependence of the signal. The results are provided as inputs to the measurement of the longitudinal diffusion constant DL, which we find to be (4.12 \(\pm\) 0.04) cm\(^2\)/s for a selection of 140keV electron recoil events in 200V/cm drift field and 2.8kV/cm extraction field. To study the systematics of our measurement we examine datasets of varying event energy, field strength, and detector volume yielding a weighted average value for the diffusion constant of (4.09 \(\pm\) 0.09) cm\(^2\) /s. The measured longitudinal diffusion constant is observed to have an energy dependence, and within the studied energy range the result is systematically lower than other results in the literature.
The DarkSide-50 experiment at the Laboratori Nazionali del Gran Sasso is a search for dark matter using a dual phase time projection chamber with 50 kg of low radioactivity argon as target. Light ...signals from interactions in the argon are detected by a system of 38 photo-multiplier tubes (PMTs), 19 above and 19 below the TPC volume inside the argon cryostat. We describe the electronics which processes the signals from the photo-multipliers, the trigger system which identifies events of interest, and the data-acquisition system which records the data for further analysis. The electronics include resistive voltage dividers on the PMTs, custom pre-amplifiers mounted directly on the PMT voltage dividers in the liquid argon, and custom amplifier/discriminators (at room temperature). After amplification, the PMT signals are digitized in CAEN waveform digitizers, and CAEN logic modules are used to construct the trigger, the data acquisition system for the TPC is based on the Fermilab "artdaq" software. The system has been in operation since early 2014.
This paper describes the design, fabrication, commissioning and use of a CALibration source Insertion System (CALIS) in the DarkSide-50 direct dark matter search experiment. CALIS deploys radioactive ...sources into the liquid scintillator veto to characterize the detector response and detection efficiency of the DarkSide-50 Liquid Argon Time Projection Chamber, and the surrounding 30 t organic liquid scintillator neutron veto. It was commissioned in September 2014 and has been used successfully in several gamma and neutron source campaigns since then. A description of the hardware and an excerpt of calibration analysis results are given below.
A Geant4-based Monte Carlo package named G4DS has been developed to simulate the response of DarkSide-50, an experiment operating since 2013 at LNGS, designed to detect WIMP interactions in liquid ...argon. In the process of WIMP searches, DarkSide-50 has achieved two fundamental milestones: the rejection of electron recoil background with a power of ~10^7, using the pulse shape discrimination technique, and the measurement of the residual 39Ar contamination in underground argon, ~3 orders of magnitude lower with respect to atmospheric argon. These results rely on the accurate simulation of the detector response to the liquid argon scintillation, its ionization, and electron-ion recombination processes. This work provides a complete overview of the DarkSide Monte Carlo and of its performance, with a particular focus on PARIS, the custom-made liquid argon response model.
We report on the cryogenic characterization of Red Green Blue - High Density (RGB-HD) SiPMs developed at Fondazione Bruno Kessler (FBK) as part of the DarkSide program of dark matter searches with ...liquid argon time projection chambers. A dedicated setup was used to measure the primary dark noise, the correlated noise, and the gain of the SiPMs at varying temperatures. A custom-made data acquisition system and analysis software were used to precisely characterize these parameters. We demonstrate that FBK RGB-HD SiPMs with low quenching resistance (RGB-HD-LR\(_q\)) can be operated from 40 K to 300 K with gains in the range \(10^5\) to \(10^6\) and noise rates on the order of a few Hz/mm\(^2\).
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