Search

Background: The pioneer transcription factor (TF) GATA4 (GATA Binding Protein 4) is expressed in multiple cardiovascular lineages and is essential for heart development. GATA4 lineage-specific occupancy in the developing heart underlies its lineage specific activities. Here, we characterized GATA4 chromatin occupancy in cardiomyocyte and endocardial lineages, dissected mechanisms that control lineage specific occupancy, and analyzed GATA4 regulation of endocardial gene expression. Methods: We mapped GATA4 chromatin occupancy in cardiomyocyte and endocardial cells of embryonic day 12.5 (E12.5) mouse heart using lineage specific, Cre-activated biotinylation of GATA4. Regulation of GATA4 pioneering activity was studied in cell lines stably overexpressing GATA4. GATA4 regulation of endocardial gene expression was analyzed using single cell RNA sequencing and luciferase reporter assays. Results: Cardiomyocyte-selective and endothelial-selective GATA4 occupied genomic regions had features of lineage specific enhancers. Footprints within cardiomyocyte- and endothelial-selective GATA4 regions were enriched for NKX2-5 (NK2 homeobox 5) and ETS1 (ETS Proto-Oncogene 1) motifs, respectively, and both of these TFs interacted with GATA4 in co-immunoprecipitation assays. In stable NIH3T3 cell lines expressing GATA4 with or without NKX2-5 or ETS1, the partner TFs re-directed GATA4 pioneer binding and augmented its ability to open previously inaccessible regions, with ETS1 displaying greater potency as a pioneer partner than NKX2-5. Single-cell RNA sequencing of embryonic hearts with endothelial cell–specific Gata4 inactivation identified Gata4 -regulated endocardial genes, which were adjacent to GATA4-bound, endothelial regions enriched for both GATA4 and ETS1 motifs. In reporter assays, GATA4 and ETS1 cooperatively stimulated endothelial cell enhancer activity. Conclusions: Lineage selective non-pioneer TFs NKX2-5 and ETS1 guide the activity of pioneer TF GATA4 to bind and open chromatin and create active enhancers and mechanistically link ETS1 interaction to GATA4 regulation of endocardial development.

Calcium handling capacity is a major gauge of cardiomyocyte maturity. Ryanodine receptor 2 (RYR2) is the predominant calcium channel that releases calcium from the sarcoplasmic reticulum/endoplasmic reticulum (SR/ER) to activate cardiomyocyte contraction. Although RYR2 was previously implied as a key regulator of cardiomyocyte maturation, the mechanisms remain unclear. The aim of this study is to solve this problem.We performed Cas9/AAV9-mediated somatic mutagenesis (CASAAV) to knockout RYR2 specifically in cardiomyocytes in mice. We conducted a genetic mosaic analysis to dissect the cell-autonomous function of RYR2 during cardiomyocyte maturation. We found that RYR2 depletion triggered ultrastructural and transcriptomic defects relevant to cardiomyocyte maturation. These phenotypes were associated with the drastic activation of ER stress pathways. The ER stress alleviator tauroursodeoxycholic acid (TUDCA) partially rescued the defects in RYR2-depleted cardiomyocytes. Overexpression of ATF4, a key ER stress transcription factor, recapitulated defects in RYR2-depleted cells. Integrative analysis of RNA-Seq and bioChIP-Seq data revealed that protein biosynthesis-related genes are the major direct downstream targets of ATF4.RYR2-regulated ER homeostasis is essential for cardiomyocyte maturation. Severe ER stress perturbs cardiomyocyte maturation primarily through ATF4 activation. The major downstream effector genes of ATF4 are related to protein biosynthesis.Dysfunctional calcium handling is a major factor contributing to cardiac pathogenesis, but the molecular mechanisms remain unclear. This study uncovered RYR2 as a new regulator of ER stress and cardiomyocyte maturation, providing significant insights to guide the development of therapeutic approaches to control cardiac pathogenesis. Because cardiomyocyte maturation is a major bottleneck in translational medicine using stem cell-derived cardiomyocytes, this study also pointed out RYR2 and ER homeostasis as potential targets to manipulate the maturity of stem cell-derived cardiomyocytes.

Cardiac excitation-contraction coupling requires dyads, the nanoscopic microdomains formed adjacent to Z-lines by apposition of transverse tubules and junctional sarcoplasmic reticulum. Disruption of dyad architecture and function are common features of diseased cardiomyocytes. However, little is known about the mechanisms that modulate dyad organization during cardiac development, homeostasis, and disease. Here, we use proximity proteomics in intact, living hearts to identify proteins enriched near dyads. Among these proteins is CMYA5, an under-studied striated muscle protein that co-localizes with Z-lines, junctional sarcoplasmic reticulum proteins, and transverse tubules in mature cardiomyocytes. During cardiac development, CMYA5 positioning adjacent to Z-lines precedes junctional sarcoplasmic reticulum positioning or transverse tubule formation. CMYA5 ablation disrupts dyad architecture, dyad positioning at Z-lines, and junctional sarcoplasmic reticulum Ca2+ release, leading to cardiac dysfunction and inability to tolerate pressure overload. These data provide mechanistic insights into cardiomyopathy pathogenesis by demonstrating that CMYA5 anchors junctional sarcoplasmic reticulum to Z-lines, establishes dyad architecture, and regulates dyad Ca2+ release.

Recent breakthroughs in cryogenic silicon detector technology allow for the observation of single electron-hole pairs released via particle interactions within the target material. This implies sensitivity to energy depositions as low as the smallest band gap, which is $\sim1.2$ eV for silicon, and therefore sensitivity to eV/$c^2$-scale bosonic dark matter and to thermal dark matter at masses below 100 MeV/$c^2$. Various interaction channels that can probe the lowest currently accessible masses in direct searches are related to standard photoelectric absorption. In any of these respective dark matter signal models any uncertainty on the photoelectric absorption cross section is propagated into the resulting exclusion limit or into the significance of a potential observation. Using first-time precision measurements of the photoelectric absorption cross section in silicon recently performed at Stanford University, this article examines the importance having accurate knowledge of this parameter at low energies and cryogenic temperatures for these dark matter searches., 9 pages, 8 figures, suppl. material

With its first flight in 2018, Micro-X became the first program to fly Transition-Edge Sensors and their SQUID readouts in space. The science goal was a high-resolution, spatially resolved X-ray spectrum of the Cassiopeia A Supernova Remnant. While a rocket pointing error led to no time on target, the data was used to demonstrate the flight performance of the instrument. The detectors observed X-rays from the on-board calibration source, but a susceptibility to external magnetic fields limited their livetime. Accounting for this, no change was observed in detector response between ground operation and flight operation. This paper provides an overview of the first flight performance and focuses on the upgrades made in preparation for reflight. The largest changes have been upgrading the SQUIDs to mitigate magnetic susceptibility, synchronizing the clocks on the digital electronics to minimize beat frequencies, and replacing the mounts between the cryostat and the rocket skin to improve mechanical integrity. As the first flight performance was consistent with performance on the ground, reaching the instrument goals in the laboratory is considered a strong predictor of future flight performance.

The Micro-X sounding rocket is a NASA funded X-ray telescope payload that completed its first flight on July 22, 2018. This event marked the first operation of Transition Edge Sensors (TESs) and their SQUID-based multiplexing readout system in space. Unfortunately, due to an ACS pointing failure, the rocket was spinning during its five minute observation period and no scientific data was collected. However, data collected from the internal calibration source marked a partial success for the payload and offers a unique opportunity to study the response of TESs and SQUIDs in space. Of particular interest is the magnetic field response of the NIST MUX06a SQUID readout system to tumbling through Earth's magnetic field. We present a model to explain the baseline response of the SQUIDs, which lead to a subset of pixels failing to "lock" for the full observational period. Future flights of the Micro-X rocket will include the NIST MUX18b SQUID system with dramatically reduced magnetic susceptibility., Comment: 6 pages, 6 figures, LTD19 conference proceedings

Micro-X is an X-ray sounding rocket payload that had its first flight on July 22, 2018. The goals of the first flight were to operate a transition edge sensor (TES) X-ray microcalorimeter array in space and take a high-resolution spectrum of the Cassiopeia A supernova remnant. The first flight was considered a partial success. The array and its time-division multiplexing readout system were successfully operated in space, but due to a failure in the attitude control system, no time on-target was acquired. A re-flight has been scheduled for summer 2022. Since the first flight, modifications have been made to the detector systems to improve noise and reduce the susceptibility to magnetic fields. The three-stage SQUID circuit, NIST MUX06a, has been replaced by a two-stage SQUID circuit, NIST MUX18b. The initial laboratory results for the new detector system will be presented in this paper., Comment: LTD proceedings, 6 pages, 3 figures, 1 table

The paucity of knowledge about cardiomyocyte maturation is a major bottleneck in cardiac regenerative medicine. In development, cardiomyocyte maturation is characterized by orchestrated structural, transcriptional, and functional specializations that occur mainly at the perinatal stage. Sarcomeres are the key cytoskeletal structures that regulate the ultrastructural maturation of other organelles, but whether sarcomeres modulate the signal transduction pathways that are essential for cardiomyocyte maturation remains unclear. To address this question, here we generated mice with cardiomyocyte-specific, mosaic, and hypomorphic mutations of α-actinin-2 (Actn2) to study the cell-autonomous roles of sarcomeres in postnatal cardiomyocyte maturation. Actn2 mutation resulted in defective structural maturation of transverse-tubules and mitochondria. In addition, Actn2 mutation triggered transcriptional dysregulation, including abnormal expression of key sarcomeric and mitochondrial genes, and profound impairment of the normal progression of maturational gene expression. Mechanistically, the transcriptional changes in Actn2 mutant cardiomyocytes strongly correlated with those in cardiomyocytes deleted of serum response factor (SRF), a critical transcription factor that regulates cardiomyocyte maturation. Actn2 mutation increased the monomeric form of cardiac α-actin, which interacted with the SRF cofactor MRTFA and perturbed its nuclear localization. Overexpression of a dominant-negative MRTFA mutant was sufficient to recapitulate the morphological and transcriptional defects in Actn2 and Srf mutant cardiomyocytes. Together, these data indicate that Actn2-based sarcomere organization regulates structural and transcriptional maturation of cardiomyocytes through MRTF-SRF signaling.

This article presents an analysis and the resulting limits on light dark matter inelastically scattering off of electrons, and on dark photon and axion-like particle absorption, using a second-generation SuperCDMS high-voltage eV-resolution detector. The 0.93 gram Si detector achieved a 3 eV phonon energy resolution; for a detector bias of 100 V, this corresponds to a charge resolution of 3% of a single electron-hole pair. The energy spectrum is reported from a blind analysis with 1.2 gram-days of exposure acquired in an above-ground laboratory. With charge carrier trapping and impact ionization effects incorporated into the dark matter signal models, the dark matter-electron cross section $\bar{\sigma}_{e}$ is constrained for dark matter masses from 0.5--$10^{4} $MeV$/c^{2}$; in the mass range from 1.2--50 eV$/c^{2}$ the dark photon kinetic mixing parameter $\varepsilon$ and the axioelectric coupling constant $g_{ae}$ are constrained. The minimum 90% confidence-level upper limits within the above mentioned mass ranges are $\bar{\sigma}_{e}\,=\,8.7\times10^{-34}$ cm$^{2}$, $\varepsilon\,=\,3.3\times10^{-14}$, and $g_{ae}\,=\,1.0\times10^{-9}$., Comment: 5 pages + title and references, 3 figures and 1 table

Cardiomyocyte (CM) maturation is an essential step in heart development that prepares the organ for robust and sustainable contractions. However, very little is known about the contribution of CM maturation to cardiac pathogenesis, partly due to the paucity of basic knowledge about maturation. For example, although calcium plays well-established roles in cardiac stress responses, whether normal calcium oscillations are required for CM maturation has not been examined. To address this question, we created mice with mosaic inactivation of ryanodine receptor 2 (RYR2), the central channel that mediates calcium release from sarcoplasmic/endoplasmic reticulum (SR/ER), in CMs. RYR2 was depleted in a small fraction of neonatal CMs by adeno-associated virus (AAV)-mediated Cas9-based somatic mutagenesis (CASAAV). The majority of CMs intentionally retained RYR2 expression, which circumvented cardiac dysfunction and death that would result from widespread calcium transient ablation. In RYR2-depleted CMs, sarcomere expansion, transverse-tubule formation, mitochondrial metabolism and maturational hypertrophy were impaired. Strikingly, these maturation defects were associated with unfolded protein response, with the activation of three major ER stress effectors: spliced Xbp1 (XBP1s), ATF6 N-terminus (ATF6N), and ATF4. Tauroursodeoxycholic acid, an ER stress-relieving drug, partially rescued the maturation defects in RYR2-depleted CMs. Over expression (OE) of XBP1s, ATF6N or ATF4 each impaired CM maturation, with phenotypic severity ranked as ATF4>XBP1s>ATF6N. ATF4 OE in neonatal CMs triggered both ultrastructural and transcriptomic changes highly correlated with RYR2 depletion phenotypes. Interestingly, ATF4 OE altered distinct transcriptomic programs in neonatal vs. adult CMs and caused ultrastructural defects only at the neonatal stage. No terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was detected upon RYR2 depletion or ATF4 OE, excluding the contribution of apoptosis to maturation defects. Collectively, these data indicate that RYR2-mediated calcium handling prevents an adverse and stage-specific impact of ER stress on CM maturation, which lead to CM dysfunction.

We present an analysis of electron recoils in cryogenic germanium detectors operated during the SuperCDMS Soudan experiment. The data are used to set new constraints on the axioelectric coupling of axionlike particles and the kinetic mixing parameter of dark photons, assuming the respective species constitutes all of the galactic dark matter. This study covers the mass range from 40 eV/c2 to 500 keV/c2 for both candidates, excluding previously untested parameter space for masses below ∼1 keV/c2. For the kinetic mixing of dark photons, values below 10−15 are reached for particle masses around 100 eV/c2; for the axioelectric coupling of axionlike particles, values below 10−12 are reached for particles with masses in the range of a few-hundred eV/c2.

We present limits on spin-independent dark matter-nucleon interactions using a $10.6$ $\mathrm{g}$ Si athermal phonon detector with a baseline energy resolution of $\sigma_E=3.86 \pm 0.04$ $(\mathrm{stat.})^{+0.19}_{-0.00}$ $(\mathrm{syst.})$ $\mathrm{eV}$. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from $93$ to $140$ $\mathrm{MeV}/c^2$, with a raw exposure of $9.9$ $\mathrm{g}\cdot\mathrm{d}$ acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches., Comment: 7 pages, 4 figures, this version includes ancillary files from official data release

After birth, cardiomyocytes (CM) acquire numerous adaptations in order to efficiently pump blood throughout an animal’s lifespan. How this maturation process is regulated and coordinated is poorly understood. Here, we perform a CRISPR/Cas9 screen in mice and identify serum response factor (SRF) as a key regulator of CM maturation. Mosaic SRF depletion in neonatal CMs disrupts many aspects of their maturation, including sarcomere expansion, mitochondrial biogenesis, transverse-tubule formation, and cellular hypertrophy. Maintenance of maturity in adult CMs is less dependent on SRF. This stage-specific activity is associated with developmentally regulated SRF chromatin occupancy and transcriptional regulation. SRF directly activates genes that regulate sarcomere assembly and mitochondrial dynamics. Perturbation of sarcomere assembly but not mitochondrial dynamics recapitulates SRF knockout phenotypes. SRF overexpression also perturbs CM maturation. Together, these data indicate that carefully balanced SRF activity is essential to promote CM maturation through a hierarchy of cellular processes orchestrated by sarcomere assembly.

Rationale: Loss-of-function studies in cardiac myocytes (CMs) are currently limited by the need for appropriate conditional knockout alleles. The factors that regulate CM maturation are poorly understood. Previous studies on CM maturation have been confounded by heart dysfunction caused by whole organ gene inactivation. Objective: To develop a new technical platform to rapidly characterize cell-autonomous gene function in postnatal murine CMs and apply it to identify genes that regulate transverse tubules (T-tubules), a hallmark of mature CMs. Methods and Results: We developed CRISPR/Cas9/AAV9-based somatic mutagenesis, a platform in which AAV9 delivers tandem guide RNAs targeting a gene of interest and cardiac troponin-T promoter–driven Cre to Rosa Cas9GFP/Cas9GFP neonatal mice. When directed against junctophilin-2 ( Jph2 ), a gene previously implicated in T-tubule maturation, we achieved efficient, rapid, and CM-specific JPH2 depletion. High-dose AAV9 ablated JPH2 in 64% CMs and caused lethal heart failure, whereas low-dose AAV9 ablated JPH2 in 22% CMs and preserved normal heart function. In the context of preserved heart function, CMs lacking JPH2 developed T-tubules that were nearly morphologically normal, indicating that JPH2 does not have a major, cell-autonomous role in T-tubule maturation. However, in hearts with severe dysfunction, both adeno-associated virus–transduced and nontransduced CMs exhibited T-tubule disruption, which was more severe in the transduced subset. These data indicate that cardiac dysfunction disrupts T-tubule structure and that JPH2 protects T-tubules in this context. We then used CRISPR/Cas9/AAV9-based somatic mutagenesis to screen 8 additional genes for required, cell-autonomous roles in T-tubule formation. We identified RYR2 (Ryanodine Receptor-2) as a novel, cell-autonomously required T-tubule maturation factor. Conclusions: CRISPR/Cas9/AAV9-based somatic mutagenesis is a powerful tool to study cell-autonomous gene functions. Genetic mosaics are invaluable to accurately define cell-autonomous gene function. JPH2 has a minor role in normal T-tubule maturation but is required to stabilize T-tubules in the failing heart. RYR2 is a novel T-tubule maturation factor.

Cardiomyocyte maturation is essential for robust heart contraction throughout life. The signaling networks governing cardiomyocyte maturation remain poorly defined. Our prior studies established the transcription factor SRF as a key regulator of the assembly of sarcomeres, the contractile unit of cardiomyocytes. Whether sarcomeres regulate other aspects of maturation remains unclear. Here we generated mice with cardiomyocyte specific, mosaic mutation of α-actinin-2 (Actn2), a key organizer of sarcomeres, to study its cell-autonomous role in cardiomyocyte maturation. In addition to the expected structural defects,Actn2mutation triggered dramatic transcriptional dysregulation, which strongly correlated with transcriptional changes observed in SRF-depleted cardiomyocytes.Actn2mutation increased monomeric actin, which perturbed the nuclear localization of the SRF cofactor MRTFA. Overexpression of a dominant-negative MRTFA mutant was sufficient to recapitulate the transcriptional and morphological defects inActn2andSrfmutant cardiomyocytes. Together, we demonstrate that ACTN2-based sarcomere assembly and MRTF-SRF signaling establish a positive feedback loop that promotes cardiomyocyte maturation.

Cardiomyocyte (CM) maturation is characterized by transcriptional, morphological and functional specializations that are essential for robust and sustained CM contractions throughout lifetime. The signal networks that govern CM maturation remain poorly defined, which obscures the role of CM maturation in inherited cardiomyopathies and myocardial regeneration and impairs efforts to engineer mature cardiac tissues in vitro . Our prior studies established the transcription factor serum response factor (SRF) as a key regulator of CM maturation: SRF regulates major CM maturation events including myofibril expansion, mitochondria biogenesis, transverse-tubule formation, and cellular hypertrophy. Myofibrillar genes were identified as direct SRF downstream targets that are required for other aspects of CM maturation. To further understand the role of myofibrils in CM maturation, here we report the generation and investigation of a floxed allele of Actn2 in mice, which encodes a central component of sarcomere Z-lines. We applied to these mice a low dose of adeno-associated virus that expressed Cre recombinase specifically in neonatal CMs to generate hearts with mosaic Actn2 mutation. This approach circumvented the confounding secondary effects of cardiac dysfunction in Actn2 mutants and revealed cell-autonomous gene functions. Strikingly, Actn2 ablation triggered dramatic transcriptional dysregulation in addition to the expected myofibrillar disassembly phenotypes in CMs, which strongly correlated with observations in SRF-depleted CMs. Actn2 mutation increased the amount of monomeric actin in CMs, which perturbed the nuclear localization of SRF cofactors MRTF-A/-B. Overexpression of a dominant-negative MRTF-A isoform was sufficient to recapitulate the transcriptional and morphological defects in Actn2 or Srf mutant CMs. Together, these data demonstrate mutual potentiation between myofibril assembly and MRTF-A/B-SRF signaling in CM maturation. This positive feedback loop underlies a novel mechanism by which mechanical forces regulate CM maturation, disruption of which likely contributes to cardiomyopathies caused by sarcomere gene mutations.

This corrects the article DOI: 10.1103/PhysRevLett.121.051301.

The Cryogenic Dark Matter Search (CDMS II) experiment aims to detect dark matter particles that elastically scatter from nuclei in semiconductor detectors. The resulting nuclear-recoil energy depositions are detected by ionization and phonon sensors. Neutrons produce a similar spectrum of low-energy nuclear recoils in such detectors, while most other backgrounds produce electron recoils. The absolute energy scale for nuclear recoils is necessary to interpret results correctly. The energy scale can be determined in CDMS II silicon detectors using neutrons incident from a broad-spectrum $^{252}$Cf source, taking advantage of a prominent resonance in the neutron elastic scattering cross section of silicon at a recoil (neutron) energy near 20 (182) keV. Results indicate that the phonon collection efficiency for nuclear recoils is $4.8^{+0.7}_{-0.9}$% lower than for electron recoils of the same energy. Comparisons of the ionization signals for nuclear recoils to those measured previously by other groups at higher electric fields indicate that the ionization collection efficiency for CDMS II silicon detectors operated at $\sim$4 V/cm is consistent with 100% for nuclear recoils below 20 keV and gradually decreases for larger energies to $\sim$75% at 100 keV. The impact of these measurements on previously published CDMS II silicon results is small., Comment: 22 pages, 17 figures, 1 table, 1 appendix

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$\cdot$day) are 74$\pm$9 for $^3$H, 1.5$\pm$0.7 for $^{55}$Fe, 17$\pm$5 for $^{65}$Zn, and 30$\pm$18 for $^{68}$Ge., 14 pages, 10 figures, 5 tables. v5 contains the extended data release (and documentation) of the CDMSlite Run 2 data as ancillary files

Background The insulin/insulin‐like growth factor/relaxin family represents a group of structurally related but functionally diverse proteins. The family member relaxin‐2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of insulin‐like peptide 6 (INSL6), another member of this protein family, in murine heart failure models using genetic loss‐of‐function and protein delivery methods. Methods and Results Insl6‐deficient and wild‐type (C57 BL /6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively, for 2 weeks. In both models, Insl6‐knockout mice exhibited greater cardiac systolic dysfunction and left ventricular dilatation. Cardiac dysfunction in the Insl6‐knockout mice was associated with more extensive cardiac fibrosis and greater expression of fibrosis‐associated genes. The continuous infusion of chemically synthesized INSL 6 significantly attenuated left ventricular systolic dysfunction and cardiac fibrosis induced by isoproterenol infusion. Gene expression profiling suggests liver X receptor/retinoid X receptor signaling is activated in the isoproterenol‐challenged hearts treated with INSL 6 protein. Conclusions Endogenous Insl6 protein inhibits cardiac systolic dysfunction and cardiac fibrosis in angiotensin II – and isoproterenol‐induced cardiac stress models. The administration of recombinant INSL 6 protein could have utility for the treatment of heart failure and cardiac fibrosis.

We present the first limits on inelastic electron-scattering dark matter and dark photon absorption using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs (CDMS HVeV, a 0.93 gram CDMS HV device). These electron-recoil limits significantly improve experimental constraints on dark matter particles with masses as low as 1 MeV/$\mathrm{c^2}$. We demonstrate a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure (0.49 gram days). These results demonstrate the scientific potential of phonon-mediated semiconductor detectors that are sensitive to single electronic excitations., 6 pages + title and references, 6 figures, includes erratum submitted to PRL and data release

We report the result of a blinded search for weakly interacting massive particles (WIMPs) using the majority of the SuperCDMS Soudan data set. With an exposure of 1690 kg d, 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 1.4×10−44 (1.0×10−44) cm2 at 46 GeV/c2. These results set the strongest limits for WIMP–germanium-nucleus interactions for masses >12 GeV/c2.

SuperCDMS SNOLAB will be a next-generation experiment aimed at directly detecting low-mass (< 10 GeV/c$^2$) 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$^{-43}$ cm$^2$ for a dark matter particle mass of 1 GeV/c$^2$, 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 $^{3}$H and naturally occurring $^{32}$Si 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/c$^2$. The iZIP detectors are relatively insensitive to variations in detector response and backgrounds, and will provide better sensitivity for dark matter particle masses (> 5 GeV/c$^2$). 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., SuperCDMS SNOLAB Projected sensitivity reach

© 2016 American Physical Society. The CDMS low ionization threshold experiment (CDMSlite) uses cryogenic germanium detectors operated at a relatively high bias voltage to amplify the phonon signal in the search for weakly interacting massive particles (WIMPs). Results are presented from the second CDMSlite run with an exposure of 70 kg day, which reached an energy threshold for electron recoils as low as 56 eV. A fiducialization cut reduces backgrounds below those previously reported by CDMSlite. New parameter space for the WIMP-nucleon spin-independent cross section is excluded for WIMP masses between 1.6 and 5.5 GeV/c2.

Long-lived alpha and beta emitters in the $^{222}$Rn decay chain on (and near) detector surfaces may be the limiting background in many experiments attempting to detect dark matter or neutrinoless double-beta decay, and in screening detectors. In order to reduce backgrounds from radon-daughter plate-out onto the wires of the BetaCage during its assembly, an ultra-low-radon cleanroom is being commissioned at Syracuse University using a vacuum-swing-adsorption radon-mitigation system. The radon filter shows ~20$\times$ reduction at its output, from 7.47$\pm$0.56 to 0.37$\pm$0.12 Bq/m$^3$, and the cleanroom radon activity meets project requirements, with a lowest achieved value consistent with that of the filter, and levels consistently < 2 Bq/m$^3$., 5 pages, 3 figures, Proceedings of Low Radioactivity Techniques (LRT) 2013, Gran Sasso, Italy, April 10-12, 2013

We comment on some misleading and biased statements appearing in the manuscript arXiv:1209.0298 ("Thermal fluctuations of magnetic nanoparticles") about the use of the damped Landau-Lifshitz equation and the kinetic Langer theory for the calculation of the relaxation rate of magnetic nanoclusters. We reiterate simple scientific arguments, part of which is well known to the whole community, demonstrating that the authors' criticisms are unfounded and that they overstate the issue of damping in the Landau-Lifshitz equation with no unanimous experimental evidence., 3 pages