The Super Cryogenic Dark Matter Search (SuperCDMS) and its predecessor CDMS have been at the forefront of the search for Weakly Interacting Massive dark matter Particles (WIMPs) for close to two ...decades. Significant improvements in detector technology have opened up the low-mass parameter space (≲ 10 GeV/c2) where the experiment broke new ground with the CDMS low ionization threshold experiment (CDMSlite). Building on this success, SuperCDMS is preparing for the next phase of the experiment to be located at SNOLAB near Sudbury, Ontario. The new experimental setup will provide space for up to ∼200 kg of target mass in a considerably lower background environment. The initial payload of about 30 kg will be a mix of germanium and silicon targets in the form of both background discriminating iZIP and low-threshold HV detectors, pushing the sensitivity towards WIMPs with even lower masses and improving the cross-section reach of SuperCDMS by more than an order of magnitude. The long-term goal is to reach the neutrino-floor below 10 GeV/c2. We present the status of and plans for SuperCDMS at SNOLAB.
Abstract Oxytocin has numerous prosocial and antipsychotic-like effects in animals. Prosocial effects of acute intranasal oxytocin administration have also been reported in human subjects. We ...conducted a randomized, placebo-controlled trial testing the effects of twice daily intranasal oxytocin treatment for 14 days on psychotic symptoms and social cognition in patients with schizophrenia. PANSS scores declined significantly and several social cognition measures improved significantly or nearly significantly in oxytocin (N = 11) but not placebo (N = 9) recipients. Our results suggest that, in addition to reducing classic psychotic symptoms, oxytocin may diminish certain social cognition deficits that are not improved by current antipsychotic medications.
Estradiol protects against brain injury, neurodegeneration, and cognitive decline. Our previous work demonstrates that physiological levels of estradiol protect against stroke injury and that this ...protection may be mediated through receptor-dependent alterations of gene expression. In this report, we tested the hypothesis that estrogen receptors play a pivotal role in mediating neuroprotective actions of estradiol and dissected the potential biological roles of each estrogen receptor (ER) subtype, ERα and ERβ, in the injured brain. To investigate and delineate these mechanisms, we used ERα-knockout (ERαKO) and ERβ-knockout (ERβKO) mice in an animal model of stroke. We performed our studies by using a controlled endocrine paradigm, because endogenous levels of estradiol differ dramatically among ERαKO, ERβKO, and wild-type mice. We ovariectomized ERαKO, ERβKO, and the respective wild-type mice and implanted them with capsules filled with oil (vehicle) or a dose of 17β-estradiol that produces physiological hormone levels in serum. One week later, mice underwent ischemia. Our results demonstrate that deletion of ERα completely abolishes the protective actions of estradiol in all regions of the brain; whereas the ability of estradiol to protect against brain injury is totally preserved in the absence of ERβ. Thus, our results clearly establish that the ERα subtype is a critical mechanistic link in mediating the protective effects of physiological levels of estradiol in brain injury. Our discovery that ERα mediates protection of the brain carries far-reaching implications for the selective targeting of ERs in the treatment and prevention of neural dysfunction associated with normal aging or brain injury.
The Super Cryogenic Dark Matter Search is one of the leading experiments in the direct search for weakly interacting massive particles in the mass range below 10 GeV/c
2
. Particles are detected in ...cryogenic semiconductor detectors; their energy deposition produces phonons and liberates charges which are measured in TES-based phonon sensors and charge-collecting electrodes. The next generation of the experiment will be deployed at SNOLAB and aims to further reduce the detection threshold to a few tens of eV by reducing the noise in the readout circuit and improving the design of the phonon sensors. Traditionally, radioactive sources are used to calibrate the energy scale and to monitor detector stability. However, in most cases, it takes a long time to accumulate enough events to identify peaks in the energy spectrum. Moreover, gammas of low energy as would be required to calibrate the bottom range of the detector’s energy range cannot penetrate the cryostat shielding. This study investigates the possibility of using pulsed infrared LEDs mounted inside the cryostat as alternative calibration source.
Estradiol is a known neurotrophic and neuroprotective factor. Our previous work demonstrated that replacement with physiological concentrations of estradiol protects the cortex against middle ...cerebral artery occlusion (MCAO)-induced cell death. The cerebral cortex exhibits caspase-dependent programmed cell death (PCD) in many models of focal cerebral ischemia. We hypothesized that estradiol attenuates PCD during stroke injury. The current study explored the temporospatial pattern of markers of PCD, their relationship to the evolution of injury, and their modulation by estradiol. Rats were ovariectomized and treated with either estradiol or vehicle. One week later, rats underwent MCAO, and brains were collected at 1, 4, 8, 16, and 24 hr. We assessed the temporospatial evolution of infarction volume, DNA fragmentation, and levels of spectrin cleavage products in ischemic cortex. Estradiol led to a delay and attenuation of injury-mediated DNA fragmentation as early as 8 hr after MCAO. Estradiol also dramatically reduced the level of the 120 kDa caspase-mediated spectrin breakdown product (SBDP120) at 4 hr but not at 8 or 16 hr. The SBDP150, produced by caspase and calpain, showed peak levels at 16 hr but was not altered by estradiol. These results strongly suggest that estradiol protects the ischemic cortex by attenuating PCD, thereby reducing caspase activity, DNA fragmentation, and subsequently, overall cell death. These studies deepen our understanding of the mechanisms underlying estrogen-mediated neuroprotection.
Estrogens are essential for normal reproductive function. In addition, they exert important, complex, and diverse nonreproductive actions on multiple tissues. Although accumulating evidence from ...basic science studies using animal models suggests that estradiol plays a critical neuroprotective role against multiple types of neurodegenerative diseases and injuries, recent clinical studies have reported either inconclusive or untoward effects of hormone therapy on the brain. We focus herein on the work that we have done during the past 6 yr that strongly suggests that low levels of estradiol therapy exert dramatic protective actions in the adult injured brain. Our results reveal that 17β-estradiol slows the progression of this injury and diminishes the extent of cell death by suppressing apoptotic cell death pathways and enhancing expression of genes that optimize cell survival. Furthermore, we have found that estrogen receptors play a pivotal functional role in neuroprotection. Together, these results carry broad implications for the selective targeting of estrogen receptors in the treatment of neurodegenerative conditions resulting from disease or injury, particularly for aging, postmenopausal women.
Estradiol protects against ischemic injury Dubal, D B; Kashon, M L; Pettigrew, L C ...
Journal of cerebral blood flow and metabolism,
11/1998, Volume:
18, Issue:
11
Journal Article
Peer reviewed
Open access
Clinical studies demonstrate that estrogen replacement therapy in postmenopausal women may enhance cognitive function and reduce neurodegeneration associated with Alzheimer's disease and stroke. This ...study assesses whether physiologic levels of estradiol prevent brain injury in an in vivo model of permanent focal ischemia. Sprague-Dawley rats were ovariectomized; they then were implanted, immediately or at the onset of ischemia, with capsules that produced physiologically low or physiologically high 17beta-estradiol levels in serum (10 or 60 pg/mL, respectively). One week after ovariectomy, ischemia was induced. Estradiol pretreatment significantly reduced overall infarct volume compared with oil-pretreated controls (mean+/-SD: oil = 241+/-88; low = 139+/-91; high = 132+/-88 mm3); this protective effect was regionally specific to the cortex, since no protection was observed in the striatum. Baseline and ischemic regional CBF did not differ between oil and estradiol pretreated rats, as measured by laser Doppler flowmetry. Acute estradiol treatment did not protect against ischemic injury. Our finding that estradiol pretreatment reduces injury demonstrates that physiologic levels of estradiol can protect against neurodegeneration.
The neutron flux induced by radioactivity at the Gran Sasso underground laboratory is revisited. We have performed calculations and Monte Carlo simulations; the results offer an independent check to ...the available experimental data reported by different authors, which vary rather widely. This study gives detailed information on the expected spectrum and on the variability of the neutron flux due to possible variations of the water content of the environment.
Searches for dark matter with cryogenic detectors are pushing to lower energy thresholds at each development stage. Consequently, new approaches for detector calibration at the proposed energy scales ...are necessary. In the case of SuperCDMS SNOLAB, energy thresholds in the range of a few eV are expected. In this paper, we are reporting R&D work for new ideas to calibrate cryogenic detectors in the eV range utilizing LEDs of various wavelengths operated at cryogenic temperatures.
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