Reversal of Fragile X Phenotypes by Manipulation of AβPP/Aβ Levels in Fmr1KO Mice

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading known genetic cause of autism. Fragile X mental retardation protein (FMRP), which is absent or expressed at substantially reduced levels in FXS, binds to and controls the postsynaptic translation of amyloid β-protein precursor (AβPP) mRNA. Cleavage of AβPP can produce β-amyloid (Aβ), a 39–43 amino acid peptide mis-expressed in Alzheimer's disease (AD) and Down syndrome (DS). Aβ is over-expressed in the brain of Fmr1KO mice, suggesting a pathogenic role in FXS. To determine if genetic reduction of AβPP/Aβ rescues characteristic FXS phenotypes, we assessed audiogenic seizures (AGS), anxiety, the ratio of mature versus immature dendritic spines and metabotropic glutamate receptor (mGluR)-mediated long-term depression (LTD) in Fmr1KO mice after removal of one App allele. All of these phenotypes were partially or completely reverted to normal. Plasma Aβ1–42 was significantly reduced in full-mutation FXS males compared to age-matched controls while cortical and hippocampal levels were somewhat increased, suggesting that Aβ is sequestered in the brain. Evolving therapies directed at reducing Aβ in AD may be applicable to FXS and Aβ may serve as a plasma-based biomarker to facilitate disease diagnosis or assess therapeutic efficacy

Results from the Super Cryogenic Dark Matter Search (SuperCDMS) experiment at Soudan

We report the result of a blinded search for Weakly Interacting Massive Particles (WIMPs) using the majority of the SuperCDMS Soudan dataset. With an exposure of 1690 kg days, a single candidate event is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP--nucleon cross section of $1.4 \times 10^{-44}$ ($1.0 \times 10^{-44}$) cm$^2$ at 46 GeV/$c^2$. These results set the strongest limits for WIMP--germanium-nucleus interactions for masses $>$12 GeV/$c^2$

Energy loss due to defect formation from \u3csup\u3e206\u3c/sup\u3ePb recoils in SuperCDMS germanium detectors

The Super Cryogenic Dark Matter Search experiment (SuperCDMS) at the Soudan Underground Laboratory studied energy loss associated with Frenkel defect formation in germanium crystals at mK temperatures using in situ 210Pb sources. We examine the spectrum of 206Pb nuclear recoils near its expected 103 keV endpoint energy and determine an energy loss of (6.08±0.18) %, which we attribute to defect formation. From this result and using TRIM simulations, we extract the first experimentally determined average displacement threshold energy of (19.7+0.6−0.5) eV for germanium. This has implications for the analysis thresholds of future germanium-based dark matter searches

Production Rate Measurement of Tritium and Other Cosmogenic Isotopes in Germanium with CDMSlite

Future direct searches for low-mass dark matter particles with germanium detectors, such as SuperCDMS SNOLAB, are expected to be limited by backgrounds from radioactive isotopes activated by cosmogenic radiation inside the germanium. There are limited experimental data available to constrain production rates and a large spread of theoretical predictions. We examine the calculation of expected production rates, and analyze data from the second run of the CDMS low ionization threshold experiment (CDMSlite) to estimate the rates for several isotopes. We model the measured CDMSlite spectrum and fit for contributions from tritium and other isotopes. Using the knowledge of the detector history, these results are converted to cosmogenic production rates at sea level. The production rates in atoms/(kg · day) are 74  ±  9 for 3H, 1.5  ±  0.7 for 55Fe, 17  ±  5 for 65Zn, and 30  ±  18 for 68Ge

Projected sensitivity of the SuperCDMS SNOLAB experiment

SuperCDMS SNOLAB will be a next-generation experiment aimed at directly detecting low-mass (\u3c 10 GeV/c2) particles that may constitute dark matter by using cryogenic detectors of two types (HV and iZIP) and two target materials (germanium and silicon). The experiment is being designed with an initial sensitivity to nuclear recoil cross sections ~ 1 x 10−43 cm2 for a dark matter particle mass of 1 GeV/c2, and with capacity to continue exploration to both smaller masses and better sensitivities. The phonon sensitivity of the HV detectors will be sufficient to detect nuclear recoils from sub-GeV dark matter. A detailed calibration of the detector response to low energy recoils will be needed to optimize running conditions of the HV detectors and to interpret their data for dark matter searches. Low-activity shielding, and the depth of SNOLAB, will reduce most backgrounds, but cosmogenically produced 3H and naturally occurring 32Si will be present in the detectors at some level. Even if these backgrounds are x10 higher than expected, the science reach of the HV detectors would be over three orders of magnitude beyond current results for a dark matter mass of 1 GeV/c2. The iZIP detectors are relatively insensitive to variations in detector response and backgrounds, and will provide better sensitivity for dark matter particle masses (\u3e 5 GeV/c2). The mix of detector types (HV and iZIP), and targets (germanium and silicon), planned for the experiment, as well as flexibility in how the detectors are operated, will allow us to maximize the low-mass reach, and understand the backgrounds that the experiment will encounter. Upgrades to the experiment, perhaps with a variety of ultra-low-background cryogenic detectors, will extend dark matter sensitivity down to the neutrino floor , where coherent scatters of solar neutrinos become a limiting background

Low-mass dark matter search with CDMSlite

The SuperCDMS experiment is designed to directly detect weakly interacting massive particles (WIMPs) that may constitute the dark matter in our Galaxy. During its operation at the Soudan Underground Laboratory, germanium detectors were run in the CDMSlite mode to gather data sets with sensitivity specifically for WIMPs with masses /c2. In this mode, a higher detector-bias voltage is applied to amplify the phonon signals produced by drifting charges. This paper presents studies of the experimental noise and its effect on the achievable energy threshold, which is demonstrated to be as low as 56 eVee (electron equivalent energy). The detector-biasing configuration is described in detail, with analysis corrections for voltage variations to the level of a few percent. Detailed studies of the electric-field geometry, and the resulting successful development of a fiducial parameter, eliminate poorly measured events, yielding an energy resolution ranging from ∼9 eVee at 0 keV to 101 eVee at ∼10 eVee. New results are derived for astrophysical uncertainties relevant to the WIMP-search limits, specifically examining how they are affected by variations in the most probable WIMP velocity and the Galactic escape velocity. These variations become more important for WIMP masses below 10 GeV/c2. Finally, new limits on spin-dependent low-mass WIMP-nucleon interactions are derived, with new parameter space excluded for WIMP masses ≲3 GeV/c