PocketWATCH: design and operation of a multi-use test bed for water Cherenkov detector components in pure and gadolinium loaded water

The PocketWATCH facility is a unique multi-purpose test bed designed to replicate the conditions of large water Cherenkov detectors. Housed at the University of Sheffield, the facility consists of a light-tight 2000 L ultrapure water tank with purification and temperature control systems. Water temperature, resistivity, and UV attenuation in the tank are monitored and shown to be stable over time. The system is also shown to be compatible with a solution of 0.2% gadolinium sulfate, allowing further utility in testing equipment bound for the next generation neutrino and nucleon decay water Cherenkov particle detectors. The relevant water quality parameters are shown to be stable whilst running in Gd-mode, thereby providing a suitable test bed for hardware development in a realistic, ex situ environment

PocketWATCH: Design and operation of a multi-use test bed for water Cherenkov detector components in pure and gadolinium loaded water

The PocketWATCH facility is a unique multi-purpose test bed designed to replicate the conditions of large water Cherenkov detectors. Housed at the University of Sheffield, the facility consists of a light-tight 2000L ultrapure water tank with purification and temperature control systems. Water temperature, resistivity, and UV attenuation in the tank are monitored and shown to be stable over time. The system is also shown to be compatible with a solution of 0.2% gadolinium sulfate, allowing further utility in testing equipment bound for the next generation neutrino and nucleon decay water Cherenkov particle detectors. The relevant water quality parameters are shown to be stable whilst running in Gd-mode, thereby providing a suitable test bed for hardware development in a realistic, ex situ environment

Characterisation of the temperature-dependent dark rate of Hamamatsu R7081-100 10" photomultiplier tubes

Dark noise is a dominant background in photomultiplier tubes (PMTs), which are commonly used in liquid-filled particle detectors for single-photon detection to see the results of particle interactions. A major contribution to dark noise is thermionic emission from the photocathode. The dark noise of Hamamatsu R7081-100 PMTs is characterised in a temperature and purity controlled water tank, with the thermionic emission contribution isolated. The results suggest that the intrinsic dark rate of PMTs does not depend on the medium, but does follow Richardson's law of thermionic emission. There are external contributions to the overall observed PMT count rate identified, but the intrinsic PMT dark rate in water matches that measured in air

Structure of the shutdown state of myosin-2

Myosin-2 is essential for processes as diverse as cell division and muscle contraction. Dephosphorylation of its regulatory light chain promotes an inactive, ‘shutdown’ state with the filament-forming tail folded onto the two heads1, which prevents filament formation and inactivates the motors2. The mechanism by which this happens is unclear. Here we report a cryo-electron microscopy structure of shutdown smooth muscle myosin with a resolution of 6 Å in the head region. A pseudo-atomic model, obtained by flexible fitting of crystal structures into the density and molecular dynamics simulations, describes interaction interfaces at the atomic level. The N-terminal extension of one regulatory light chain interacts with the tail, and the other with the partner head, revealing how the regulatory light chains stabilize the shutdown state in different ways and how their phosphorylation would allow myosin activation. Additional interactions between the three segments of the coiled coil, the motor domains and the light chains stabilize the shutdown molecule. The structure of the lever in each head is competent to generate force upon activation. This shutdown structure is relevant to all isoforms of myosin-2 and provides a framework for understanding their disease-causing mutations

Lowering the energy threshold in COSINE-100 dark matter searches

COSINE-100 is a dark matter detection experiment that uses NaI(Tl) crystal detectors operating at the Yangyang underground laboratory in Korea since September 2016. Its main goal is to test the annual modulation observed by the DAMA/LIBRA experiment with the same target medium. Recently DAMA/LIBRA has released data with an energy threshold lowered to 1 keV, and the persistent annual modulation behavior is still observed at 9.5$\sigma$. By lowering the energy threshold for electron recoils to 1 keV, COSINE-100 annual modulation results can be compared to those of DAMA/LIBRA in a model-independent way. Additionally, the event selection methods provide an access to a few to sub-GeV dark matter particles using constant rate studies. In this article, we discuss the COSINE-100 event selection algorithm, its validation, and efficiencies near the threshold

Measurement of directional range components of nuclear recoil tracks in a fiducialised dark matter detector

We present results from the first measurement of axial range components of fiducialized neutron induced nuclear recoil tracks using the DRIFT directional dark matter detector. Nuclear recoil events are fiducialized in the DRIFT experiment using temporal charge carrier separations between different species of anions in 30:10:1 Torr of CS$_2$:CF$_4$:O$_2$ gas mixture. For this measurement, neutron-induced nuclear recoil tracks were generated by exposing the detector to $^{252}$Cf source from different directions. Using these events, the sensitivity of the detector to the expected axial directional signatures were investigated as the neutron source was moved from one detector axis to another. Results obtained from these measurements show clear sensitivity of the DRIFT detector to the axial directional signatures in this fiducialization gas mode

A cryo-EM grid preparation device for time-resolved structural studies

Structural biology generally provides static snapshots of protein conformations that can provide information on the functional mechanisms of biological systems. Time-resolved structural biology provides a means to visualize, at near-atomic resolution, the dynamic conformational changes that macromolecules undergo as they function. X-ray free-electron-laser technology has provided a powerful tool to study enzyme mechanisms at atomic resolution, typically in the femtosecond to picosecond timeframe. Complementary to this, recent advances in the resolution obtainable by electron microscopy and the broad range of samples that can be studied make it ideally suited to time-resolved approaches in the microsecond to millisecond timeframe to study large loop and domain motions in biomolecules. Here we describe a cryo-EM grid preparation device that permits rapid mixing, voltage-assisted spraying and vitrification of samples. It is shown that the device produces grids of sufficient ice quality to enable data collection from single grids that results in a sub-4 Å reconstruction. Rapid mixing can be achieved by blot-and-spray or mix-and-spray approaches with a delay of ∼10 ms, providing greater temporal resolution than previously reported mix-and-spray approaches

Large-scale computations on histology images reveal grade-differentiating parameters for breast cancer

BACKGROUND: Tumor classification is inexact and largely dependent on the qualitative pathological examination of the images of the tumor tissue slides. In this study, our aim was to develop an automated computational method to classify Hematoxylin and Eosin (H&E) stained tissue sections based on cancer tissue texture features. METHODS: Image processing of histology slide images was used to detect and identify adipose tissue, extracellular matrix, morphologically distinct cell nuclei types, and the tubular architecture. The texture parameters derived from image analysis were then applied to classify images in a supervised classification scheme using histologic grade of a testing set as guidance. RESULTS: The histologic grade assigned by pathologists to invasive breast carcinoma images strongly correlated with both the presence and extent of cell nuclei with dispersed chromatin and the architecture, specifically the extent of presence of tubular cross sections. The two parameters that differentiated tumor grade found in this study were (1) the number density of cell nuclei with dispersed chromatin and (2) the number density of tubular cross sections identified through image processing as white blobs that were surrounded by a continuous string of cell nuclei. Classification based on subdivisions of a whole slide image containing a high concentration of cancer cell nuclei consistently agreed with the grade classification of the entire slide. CONCLUSION: The automated image analysis and classification presented in this study demonstrate the feasibility of developing clinically relevant classification of histology images based on micro- texture. This method provides pathologists an invaluable quantitative tool for evaluation of the components of the Nottingham system for breast tumor grading and avoid intra-observer variability thus increasing the consistency of the decision-making process

Background Assay and Rejection in DRIFT

The DRIFT-IId dark matter detector is a m3-scale low-pressure TPC with directional sensitivity to WIMP-induced nuclear recoils. Its primary backgrounds were due to alpha decays from contamination on the central cathode. Efforts to reduce these backgrounds led to replacing the 20 μm wire central cathode with one constructed from 0.9 μm aluminized mylar, which is almost totally transparent to alpha particles. Detailed modeling of the nature and origin of the remaining backgrounds led to an in-situ, ppt-sensitive assay of alpha decay backgrounds from the central cathode. This led to further improvements in the thin-film cathode resulting in over 2 orders of magnitude reduction in backgrounds compared to the wire cathode. Finally, the addition of O2 to CS2 gas was found to produce multiple species of electronegative charge carriers, providing a method to determine the absolute position of nuclear recoils and reject all known remaining backgrounds while retaining a high efficiency for nuclear recoil detection