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Supplementary Figures 1 - 8, Tables 1 - 3

Supplementary Methods

Estrogen receptor alpha (ERα) is a ligand-dependent master transcriptional regulator and key driver of breast cancer pathology. Small molecule hormones and competitive antagonists favor unique ERα conformational ensembles that elicit ligand-specific transcriptional programs in breast cancer and other hormone-responsive tissues. By affecting disparate ligand binding domain structural features, unconventional ligand scaffolds can redirect ERα genomic binding patterns to engage novel therapeutic transcriptional programs. To improve our understanding of these ERα structure-transcriptional relationships, we have developed a series of chemically unconventional antagonists based on the antiestrogens RAD1901 and lasofoxifene. High-resolution x-ray co-crystal structures show that these molecules affect both classical and unique structural motifs within the ERα ligand binding pocket. They show moderately reduced antagonistic potencies on ERα genomic activities but are effective anti-proliferative agents in luminal breast cancer cells. Interestingly, they show SERM-like ERα accumulation in breast cancer cells but lack uterotrophic activities in an endometrial cell line. RNA sequencing shows that the lead molecules mediate transcriptional pathways similar to fulvestrant and other SERDs in these cells. This advance shows that fulvestrant-like genomic activities can be achieved without affecting ERα accumulation in breast cancer cells.

Breast and prostate cancer are the leading cancer diagnoses for women and men, respectively, second only to cutaneous cancers. Breast and prostate cancer arise from aberrant estrogen/estrogen receptor (ER) and testosterone/androgen receptor signaling (AR), respectively. These sex hormone receptors are members of the steroid hormone receptor family, which also includes the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and progesterone receptor (PR). Although these receptors canonically function through homodimerization, recent evidence has suggested that receptor crosstalk can amplify or dampen the actions of heterologous receptors. However, these interactions have not been extensively studied in all possible combinations of steroid hormone receptor crosstalk. In this project, we hypothesize that heterodimerization may amplify or repress the transcriptional response(s) elicited by the various receptor complexes depending upon conditions such as concentration of ligands, type of ligand, physiological states, and the types/functions of promoter regions. To test this hypothesis, we investigated the significance of ligand-induced interactions between different homo- and heterodimer combinations of AR, ARV7, GR, MR, PR, and ERα in HEK293 cells using IncuCyte live-cell imaging and NanoBRET technology. Ultimately, the combination of transfection experiments, live-cell imaging, and NanoBRET assays provided insight into which combination of steroid receptors successfully interact to amplify (or dampen) the HaloTag expression, luminescence intensity at 450nM (i.e., NanoLuc expression), and NanoBRET ratio (i.e., acceptor emission luminescence at 610nM divided by donor emission luminescence at 450nM) in HEK293 cells. Our studies revealed that heterodimerization of ERα-PR, ERα-MR, AR-GR, AR-PR, ARV7-MR, ARV7-PR, and GR-MR produced significant ligand-induced changes in signaling intensity compared to no ligand conditions for each fusion protein construct. Additionally, to demonstrate the value of the NanoBRET method for modelling clinically relevant disease conditions, we assessed the physical interaction of ERα and PR in the context of the ERα Y537S mutation - a mutation associated with endocrine therapy resistance in breast cancer that results in a constitutively active ERα. The results showed that ERα-Y537S mutation increases ERα/PR physical interaction upon PR-B stimulation in a NanoBRET proximity-based assay. Future directions include testing these interactions in breast and prostate cancer cell lines and identifying the receptors’ localization within the cell, the results of which may be of clinical importance. Citation Format: Amira Ishag-Osman, David Hosfield, Rosemary Huggins, Geoffrey Greene. Evaluating nuclear receptor heterodimerization using live cell proximity assays: Implications for novel therapeutic approaches for hormone driven cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3439.

Background: Fiber intake has been shown to be higher in normal weight children compared to overweight and obese children. However, the effect of family-based interventions have been inconclusive. Objective: To determine if a family-based weight management intervention, which has been successful at lowering BMI Z-score, has an effect on energy adjusted dietary fiber intake and other markers of dietary quality. Methods: Sixty-six children ages 6-11 and their guardians participated in a 16 week nutrition and physical activity intervention. Guardians and children completed a food frequency questionnaire (FFQ) during the first and last sessions. The FFQ provided information about fiber, macronutrients and micronutrients. Results: Children increased fiber from 8.65±2.00g/1000kcal to 9.48±2.26g/1000kcal (p

The violation of baryon number, B , is an essential ingredient for the preferential creation of matter over antimatter needed to account for the observed baryon asymmetry in the Universe. However, such a process has yet to be experimentally observed. The HIBEAM/NNBAR program is a proposed two-stage experiment at the European Spallation Source to search for baryon number violation. The program will include high-sensitivity searches for processes that violate baryon number by one or two units: free neutron–antineutron oscillation ( n → n ̄ ) via mixing, neutron–antineutron oscillation via regeneration from a sterile neutron state ( n → [ n ′ , n ̄ ′ ] → n ̄ ), and neutron disappearance (n → n′); the effective Δ B = 0 process of neutron regeneration ( n → [ n ′ , n ̄ ′ ] → n ) is also possible. The program can be used to discover and characterize mixing in the neutron, antineutron and sterile neutron sectors. The experiment addresses topical open questions such as the origins of baryogenesis and the nature of dark matter, and is sensitive to scales of new physics substantially in excess of those available at colliders. A goal of the program is to open a discovery window to neutron conversion probabilities (sensitivities) by up to three orders of magnitude compared with previous searches. The opportunity to make such a leap in sensitivity tests should not be squandered. The experiment pulls together a diverse international team of physicists from the particle (collider and low energy) and nuclear physics communities, while also including specialists in neutronics and magnetics.

We show unequivocal evidence for formation of He_{2}^{*} excimers in liquid He II created by ionizing radiation produced through neutron capture. Laser beams induce fluorescence of the excimers. The fluorescence is recorded at a rate of 55.6 Hz by a camera. The location of the fluorescence is determined with an uncertainty of 5 μm. The technique provides an opportunity to record the flow of He_{2}^{*} excimers in a medium with very small viscosity and enables measurement of turbulence around macroscopic liter size objects or vortex matter in three dimensions.

The NPDGamma experiment measures the parity-violating asymmetry in $\gamma$-ray emission in the capture of polarized neutrons on liquid parahydrogen. The sensitivity to the asymmetry for each detector in the array is used as a parameter in the extraction of the physics asymmetry from the measured data. The detector array is approximately cylindrically symmetric around the target and a step-wise sinusoidal function has been used for the sensitivity in the previous iteration of the NPDGamma experiment, but deviations from cylindrical symmetry necessitate the use of a Monte Carlo model to determine corrections to the geometrical factors. For the calculations, source code modifications to MCNPX were done in order to calculate the sensitivity of each cesium iodide detector to the physics asymmetry. We describe the MCNPX model and results from calculations and how the results are validated through measurement of the parity violating asymmetry of $\gamma$-rays from neutron capture on chlorine., Comment: 10 pages, 10 figures

The Alpha-Gamma device at the National Institute of Standards and Technology (NIST) utilizes neutron capture on a totally absorbing 10B deposit to measure the absolute neutron flux of a monochromatic cold neutron beam. Gammas produced by the boron capture are counted using high purity germanium detectors, which are calibrated using a well-measured 239Pu alpha source and the alpha-to-gamma ratio from neutron capture on a thin 10B target. This device has been successfully operated and used to calibrate the neutron flux monitor for the BL2 neutron lifetime experiment at NIST. It is also being used for a measurement of the 6Li(n,t)4He cross section. We shall present its principle of operation along with the current and planned projects involving the Alpha-Gamma device, including the recalibration of the U.S. national neutron standard NBS-1 and (n,f) cross section measurements of 235U.

We report the first observation of the parity-violating gamma-ray asymmetry A_{γ}^{np} in neutron-proton capture using polarized cold neutrons incident on a liquid parahydrogen target at the Spallation Neutron Source at Oak Ridge National Laboratory. A_{γ}^{np} isolates the ΔI=1, ^{3}S_{1}→^{3}P_{1} component of the weak nucleon-nucleon interaction, which is dominated by pion exchange and can be directly related to a single coupling constant in either the DDH meson exchange model or pionless effective field theory. We measured A_{γ}^{np}=[-3.0±1.4(stat)±0.2(syst)]×10^{-8}, which implies a DDH weak πNN coupling of h_{π}^{1}=[2.6±1.2(stat)±0.2(syst)]×10^{-7} and a pionless EFT constant of C^{^{3}S_{1}→^{3}P_{1}}/C_{0}=[-7.4±3.5(stat)±0.5(syst)]×10^{-11} MeV^{-1}. We describe the experiment, data analysis, systematic uncertainties, and implications of the result.

This paper summarizes the relevant theoretical developments, outlines some ideas to improve experimental searches for free neutron-antineutron oscillations, and suggests avenues for future improvement in the experimental sensitivity., Comment: Submitted to Physics Reports

© 2019 IOP Publishing Ltd and Sissa Medialab. A cryogenic apparatus is described that enables a new experiment, nEDM@SNS, with a major improvement in sensitivity compared to the existing limit in the search for a neutron Electric Dipole Moment (EDM). This apparatus uses superfluid 4He to produce a high density of Ultra-Cold Neutrons (UCN) which are contained in a suitably coated pair of measurement cells. The experiment, to be operated at the Spallation Neutron Source at Oak Ridge National Laboratory, uses polarized 3He from an Atomic Beam Source injected into the superfluid 4He and transported to the measurement cells where it serves as a co-magnetometer. The superfluid 4He is also used as an insulating medium allowing significantly higher electric fields, compared to previous experiments, to be maintained across the measurement cells. These features provide an ultimate statistical uncertainty for the EDM of 2-3× 10-28 e-cm, with anticipated systematic uncertainties below this level.

Accurately measuring the neutron beam polarization of a high flux, large area neutron beam is necessary for many neutron physics experiments. The Fundamental Neutron Physics Beamline (FnPB) at the Spallation Neutron Source (SNS) is a pulsed neutron beam that was polarized with a supermirror polarizer for the NPDGamma experiment. The polarized neutron beam had a flux of $\sim10^9$ neutrons per second per cm$^2$ and a cross sectional area of 10$\times$12~cm$^2$. The polarization of this neutron beam and the efficiency of a RF neutron spin rotator installed downstream on this beam were measured by neutron transmission through a polarized $^{3}$He neutron spin-filter. The pulsed nature of the SNS enabled us to employ an absolute measurement technique for both quantities which does not depend on accurate knowledge of the phase space of the neutron beam or the $^{3}$He polarization in the spin filter and is therefore of interest for any experiments on slow neutron beams from pulsed neutron sources which require knowledge of the absolute value of the neutron polarization. The polarization and spin-reversal efficiency measured in this work were done for the NPDGamma experiment, which measures the parity violating $\gamma$-ray angular distribution asymmetry with respect to the neutron spin direction in the capture of polarized neutrons on protons. The experimental technique, results, systematic effects, and applications to neutron capture targets are discussed., Comment: 13 pages, 14 figures, 2 tables

We describe the Fundamental Neutron Physics Beamline (FnPB) facility located at the Spallation Neutron Source at Oak Ridge National Laboratory. The FnPB was designed for the conduct of experiments that investigate scientific issues in nuclear physics, particle physics, astrophysics and cosmology using a pulsed slow neutron beam. We present a detailed description of the design philosophy, beamline components, and measured fluxes of the polychromatic and monochromatic beams.

While intense reactor based sources of ultra-cold neutrons have been in operation for approximately three decades, it is only in the last few years that practical sources of UCN have been realized at spallation sources. Existing and proposed spallation based UCN sources employ two distinct strategies. In the first, the UCN converter (superfluid 4He, or solid D2) is placed in the immediate vicinity of the spallation target. In the second, a converter (usually superfluid He) is placed at the output end of a cold neutron guide fed by the spallation target cold source. Both of these approaches are considered in relation to the European Long Pulse Spallation Source.

The NPDGamma experiment measures the parity-violating (PV) gamma asymmetry from polarized cold neutrons captured on protons at the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory (ORNL). The (PV) neutron spin asymmetry A γ of photons from polarized cold neutron capture on protons is proportional to the ΔI=1 long range weak meson coupling $h_{\pi }^{1}$ between nucleons in the hadronic weak interaction (HWI). Liquid para-hydrogen production data taking concluded in April 2014 and once the background aluminum asymmetry measurements are complete, the PV asymmetry A γ can be extracted. Preliminary results of the analysis of A γ are presented.

Novel experimental techniques are required to make the next big leap in neutron electric dipole moment experimental sensitivity, both in terms of statistics and systematic error control. The nEDM experiment at the Spallation Neutron Source (nEDM@SNS) will implement the scheme of Golub & Lamoreaux [Phys. Rep., 237, 1 (1994)]. The unique properties of combining polarized ultracold neutrons, polarized $^3$He, and superfluid $^4$He will be exploited to provide a sensitivity to $\sim 10^{-28}\,e{\rm \,\cdot\, cm}$. Our cryogenic apparatus will deploy two small ($3\,{\rm L}$) measurement cells with a high density of ultracold neutrons produced and spin analyzed in situ. The electric field strength, precession time, magnetic shielding, and detected UCN number will all be enhanced compared to previous room temperature Ramsey measurements. Our $^3$He co-magnetometer offers unique control of systematic effects, in particular the Bloch-Siegert induced false EDM. Furthermore, there will be two distinct measurement modes: free precession and dressed spin. This will provide an important self-check of our results. Following five years of "critical component demonstration," our collaboration transitioned to a "large scale integration" phase in 2018. An overview of our measurement techniques, experimental design, and brief updates are described in these proceedings., Submitted to proceedings of PPNS 2018 - International Workshop on Particle physics at Neutron Sources (https://www.webofconferences.org/epj-web-of-conferences-forthcoming-conferences/1148-ppns-2018)

A precise value of the neutron lifetime is important in several areas of physics, including determinations of the quark-mixing matrix element |Vud|, related tests of the Standard Model, and predictions of light element abundances in Big Bang Nucleosynthesis models. We report the progress on a new measurement of the neutron lifetime utilizing the cold neutron beam technique. Several experimental improvements in both neutron and proton counting that have been developed over the last decade are presented. This new effort should yield a final uncertainty on the lifetime of 1 s with an improved understanding of the systematic effects.

Neutron beta decay is one of the most fundamental processes in nuclear physics and provides sensitive means to uncover the details of the weak interaction. Neutron beta decay can evaluate the ratio of axial-vector to vector coupling constants in the standard model, $\lambda = g_A / g_V$, through multiple decay correlations. The Nab experiment will carry out measurements of the electron-neutrino correlation parameter $a$ with a precision of $\delta a / a = 10^{-3}$ and the Fierz interference term $b$ to $\delta b = 3\times10^{-3}$ in unpolarized free neutron beta decay. These results, along with a more precise measurement of the neutron lifetime, aim to deliver an independent determination of the ratio $\lambda$ with a precision of $\delta \lambda / \lambda = 0.03\%$ that will allow an evaluation of $V_{ud}$ and sensitively test CKM unitarity, independent of nuclear models. Nab utilizes a novel, long asymmetric spectrometer that guides the decay electron and proton to two large area silicon detectors in order to precisely determine the electron energy and an estimation of the proton momentum from the proton time of flight. The Nab spectrometer is being commissioned at the Fundamental Neutron Physics Beamline at the Spallation Neutron Source at Oak Ridge National Lab. We present an overview of the Nab experiment and recent updates on the spectrometer, analysis, and systematic effects., Comment: Presented at PPNS2018

A new bender supermirror polarizer is used to polarize the cold neutron beam at the Fundamental Neutron Physics Beamline at the Spallation Neutron Source. We present the design of a compensation magnet that was built around the polarizer to minimize the polarizer fringe fields that could compromise the magnetic field requirements of the NPDGamma experiment for the field uniformity in the spin rotator and the field direction in the liquid hydrogen target located downstream from the polarizer. The entire magnetic field environment of the experiment has been analyzed using a finite-element model. Measurements of the magnetic field gradients and field direction have been carried out and the results are less than the upper limits required in the experiment. According to the results the compensated fields meet the stringent magnetic field requirements of the experiment defined by the systematic errors that have to be well below the statistical uncertainty of 10 −8 in our main observable, the gamma asymmetry in neutron capture on hydrogen. We describe the design of the magnetic field, the construction of the compensation magnet, and we compare results of the field measurements with the results from the model.

Recent studies have identified somatic ESR1 mutations in patients with metastatic breast cancer (MBC) and found some of them to promote estrogen-independent activation of the receptor. The degree to which all recurrent mutants can drive estrogen-independent activities and reduced sensitivity to ER antagonists like fulvestrant is not established. In this report, we characterize the spectrum of ESR1 mutations from over 900 patients. ESR1 mutations were detected in 10%, with D538G being the most frequent (36%), followed by Y537S (14%). Several novel, activating mutations were also detected (e.g. L469V, V422del, Y537D). While many mutations lead to constitutive activity and reduced sensitivity to ER antagonists, only select mutants such as Y537S caused a magnitude of change associated with fulvestrant resistance in vivo. Correspondingly, tumors driven by Y537S, but not D5358G, E380Q or S463P were less effectively inhibited by fulvestrant than more potent and bioavailable antagonists including AZD9496. These data point to a need for antagonists with optimal pharmacokinetic properties to realize clinical efficacy against certain ESR1 mutants.

The decay of the free neutron into a proton, electron, and antineutrino is the prototype semileptonic weak decay and is the simplest example of nuclear beta decay. It played a key role in the early Universe as it determined the ratio of neutrons to protons during the era of primordial light element nucleosynthesis. Neutron decay is physically related to important processes in solar physics and neutrino detection. The mean neutron lifetime has been the subject of more than 20 major experiments done, using a variety of methods, between 1950 and the present. The most precise recent measurements have stated accuracies approaching 0.1%, but are not in good agreement as they differ by as much as $5\ensuremath{\sigma}$ using quoted uncertainties. The history of neutron lifetime measurements is reviewed and the different methods used are described, giving important examples of each. The discrepancies and some systematic issues in the experiments that may be responsible are discussed, and it is shown by means of global averages that the neutron lifetime is likely to lie in the range of 880--884 s. Plans and prospects for future experiments are considered that will address these systematic issues and improve our knowledge of the neutron lifetime.

Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases and is more prevalent among young women and African American women. SHC1 (Src Homology 2 Domain Containing Transforming Protein 1) is an adaptor protein that can transmit cell surface receptor signaling and activate the Ras-ERK pathway. SHC1 is found to be overexpressed in breast cancers and is important in the regulation of tumor progression and drug resistance in ER+ breast cancer. Elevated SHC1 correlates with poor prognosis in breast cancer patients. However, the biological significance of SHC1 in TNBC is not known. In this study, we performed siRNA-mediated knockdown to determine the importance of SHC1 in cell proliferation and drug response in TNBC. We found that although siSHC1 slightly inhibited the tumor growth of TNBC cells, siSHC1 + paclitaxel significantly decreased cell proliferation and increased caspase-3/7 activity in vitro. In invasion assays, siSHC1 significantly decreased the invasion of TNBC cells. To better understand the systemic regulation by SHC1, proteomic analysis was performed after siSHC1 or Scr transfection. Pathway analysis revealed the involvement of PI3K/AKT, FAK, and actin cytoskeleton pathways, by disruption of EGFR and integrin β1 signaling, in the control of TNBC progression and drug sensitivity. In tumor explant studies, siSHC1 significantly enhanced paclitaxel-induced tumor shrinkage and reduced lung metastasis. Our data suggest that SHC1 is a potential therapeutic target in TNBC. Citation Format: Ya-Fang Chang, Elizabeth Cordell, Yuhao Wang, Geoffrey Greene. Disruption of EGFR and integrin b1 signaling in triple-negative breast cancer through targeting SHC1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1900.

We discuss the coherent nature of neutron interactions and properties of low-energy neutrons with the view of the possibility to search for “anomalous” forces with ranges from nuclear sizes up to the macroscopic scale.

The NPDGamma collaboration has recently completed the first phase of a measurement to determine the size of the weak nucleon–nucleon interaction from cold neutron capture on a liquid hydrogen target. In the framework of the nearly 30 year old DDH model [B. Desplanques, J.F. Donoghue, B.R. Holstein, Annals of Physics 124 (1980) 449], the measured process is explained in terms of the weak pion–nucleon coupling, while the framework of modern effective field theory parameterizes the measured process in terms of the S 1 3 - P 1 3 , long range transition (essentially the Danilov parameter ρ t ) [S.L. Zhu et al., Nuclear Physics A 748 (2005) 435; C.-P. Liu, Phys. Rev. C 75 (2007) 065501]. The couplings in terms of either model are directly proportional to the parity violating up-down asymmetry in the angular distribution of gamma rays with respect to the neutron spin direction in the reaction n ⇒ + p → d + γ . The asymmetry has a predicted size of 5 × 10 - 8 and the aim of the NPDGamma collaboration is to measure it to 20%. The first phase of the measurement was completed at the Los Alamos National Laboratory Neutron Science Center Spallation Source with a preliminary result of ( - 1.1 ± 2.1 stat . ± 0.2 sys . ) × 10 - 7 . Here, we report on the measurements and the results obtained so far. The experiment is currently being installed at the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory, for the remainder of its run time.

The optimization of the ballistic guide design for the SNS Fundamental Neutron Physics Beamline 8.9 A line is described. With a careful tuning of the shape of the curve for the tapered section and the width of the straight section, this optimization resulted in more than 75% increase in the neutron flux exiting the 33 m long guide over a straight m=3.5 guide with the same length., Comment: 21 pages, 13 figures; added a paragraph on existing ballistic guides to respond to referee comments; accepted for publication in Nuclear Inst. and Methods in Physics Research, A

Polarized neutrons provide a powerful tool for research at today's continuous neutron sources, permitting unique information to be obtained from neutron-scattering experiments and in the area of fundamental neutron physics. The information obtained is indispensable to important areas of current research such as magnetism, spin fluctuations in correlated-electron materials, nanoscience, astrophysics, and cosmology. Unfortunately, the polarized neutron capabilities that already exist at reactor neutron sources, mainly in Europe, cannot be transferred directly to pulsed spallation sources because many of the devices used at reactors to manipulate neutron spins operate only at a single neutron wavelength or with a neutron beam of limited divergence. Both of these restrictions must be overcome for devices to be useful at pulsed spallation sources. This report identifies the significant R&D efforts that will be required to achieve these goals. These efforts must be undertaken now, if they are to be useful early...

The Spallation Neutron Source (SNS), currently under construction at Oak Ridge National Laboratory with an anticipated start-up in early 2006, will provide the most intense pulsed beams of cold neutrons in the world. At a projected power of 1.4 MW, the time averaged fluxes and fluences of the SNS will approach those of high flux reactors. One of the flight paths on the cold, coupled moderator will be devoted to fundamental neutron physics. The fundamental neutron physics beamline is anticipated to include two beam-lines; a broad band cold beam, and a monochromatic beam of 0.89 nm neutrons for ultracold neutron (UCN) experiments. The fundamental neutron physics beamline will be operated as a user facility with experiment selection based on a peer reviewed proposal process. An initial program of five experiments in neutron decay, hadronic weak interaction and time reversal symmetry violation have been proposed.

We have measured the brightness of the Flight Path 12 upstream/back-scattering partially coupled cold hydrogen moderator at LANSCE. This measurement was performed in the neutron energy range of 0.8–76.9 meV by using a time-of-flight technique in conjunction with a two-pinhole collimator system. Cold neutrons were observed with a redundant 6Li-loaded glass scintillation detector having an efficiency of close to unity. The detector viewed an area of 0.93 cm2 on the center of the 12×12 cm2 moderator surface. A maximum brightness of 1.25×108 neutrons s−1 sr−1 cm−2 meV−1 μA−1 was measured at 3.3-meV neutron energy. Statistical and systematic errors of the measurement are 3% and 7%, respectively. The measured brightness is compared to the result of a model calculation and there is a significant disagreement, by a factor of 1.5 at the peak. The performance of the m=3 supermirror neutron guide system on Flight Path 12 was also studied with the two pinhole-detector system.

We detail the design and operation of an electrical substitution radiometer, which measures the absolute fluence of thermal neutron beams based on neutron absorption in a 6Li-rich metallic alloy. We demonstrate that the device possesses a linear response to electrical power in the 50–500 nW range with better than 0.1% absolute accuracy and negligible zero offset. We show the response of the radiometer to a 3 meV neutron beam. We compare the noise of the radiometer to the noise observed upstream in a thin rate monitor and show that the radiometer noise is understood quantitatively. We establish that the radiometer measures neutron rates above 105 s−1 to an absolute accuracy of 0.1%.

The purpose of this focus group research was to identify themes related to fruit and vegetable consumption in older adults that could be used as the basis for instrument development. The Transtheoretical Model of Behavior Change (TTM) was used as a framework to guide this research. Adults over the age of 60 completed a food frequency screener, and were designated into “low” and “high” fruit and vegetable intake groups. Participants responded to some general as well as stage-specific questions, dependent upon group. Data were analyzed by two independent researchers, and level of agreement was consistently high. Data reduction was accomplished by identification of inductively derived themes. The derived themes made conceptual and operational sense, and were used as a basis for development of quantitative measures related to fruit and vegetable consumption of older adults. Instrument development represents an exciting application of focus group research that deserves increased attention.

The Nab experiment will measure the correlation a between the momenta of the beta particle and antineutrino in neutron decay as well as the Fierz term b which distorts the beta spectrum.

The achievable uncertainty in neutron lifetime measurements using the beam technique has been limited by the uncertainty in the determination of the neutron density in the decay volume. In the Sussex-ILL-NIST series of beam lifetime experiments, the density was determined with a neutron fluence mon itor that detected the charged particle products from neutron absorption in a thin layer of 6Li or lOB. In each of the experiments, the absolute detection efficiency of the neutron monitor was determined from the measured density of the neutron absorber, the thermal neutron cross section for the absorbing ma terial, and the solid angle of the charged particle detectors. The efficiency of the neutron monitor used in the most recent beam lifetime experiment has since been measured directly by operating it on a monochromatic neutron beam in which the total neutron rate is determined with a totally absorbing neutron detector. The absolute nature of this technique does not rely on any knowl edge of neutron absorption cross sections or a measurement of the density of the neutron absorbing deposit. This technique has been used to measure the neutron monitor efficiency to 0.06% uncertainty. VVe show that a new monitor and absolute neutron detector employingmore » the same technique would be capable of achieving determining neutron fluence to an uncertainty of 0.01%.« less

The results of experiments and calculations for a solid-deuterium UCN source are presented. It was experimentally shown that the UCN yield is increased by a factor 3 at the solidification of liquid deuterium and a factor 10 at a temperature 10 K, with respect to the liquid phase. The gain factor for UCN yield with respect to hydrogen gas or deuterium gas at room temperature is equal to 1230.

A 23-year-old man presented with fever, dyspnea, nonproductive cough, left eye redness, reduced vision, and bilateral ear pain and tenderness. The symptoms had begun two days earlier, eight days after he was discharged from the hospital with a presumptive diagnosis of Still's disease. He was first seen a month before the current admission for complaints of fever (as high as 39.4 degrees C), nonproductive cough, and asymmetric arthritis. The workup at that time included arthrocentesis of the right knee. Analysis of the joint fluid showed 7,500 white blood cells/mm3 and no crystals. A gram stain and culture of the fluid were negative. HIV and hepatitis tests, bone marrow biopsy and culture, transesophageal echocardiography, abdominal computed tomography, radionuclide bone scanning, and rheumatologic tests failed to identify the problem. The development of an evanescent macular pink rash on day 15 suggested the possibility of Still's disease. Treatment with prednisone (40 mg po qd) was initiated, and the patient was discharged on day 19.

The most precise determination of the neutron lifetime using the beam method was completed in 2005 and reported a result of $\tau_n = (886.3 \pm 1.2 [\textrm{stat}] \pm 3.2 [\textrm{syst}])$ s. The dominant uncertainties were attributed to the absolute determination of the fluence of the neutron beam (2.7 s). The fluence was measured with a neutron monitor that counted the neutron-induced charged particles from absorption in a thin, well-characterized 6Li deposit. The detection efficiency of the monitor was calculated from the areal density of the deposit, the detector solid angle, and the evaluated nuclear data file, ENDF/B-VI 6Li(n,t)4He thermal neutron cross section. In the current work, we have measured the detection efficiency of the same monitor used in the neutron lifetime measurement with a second, totally-absorbing neutron detector. This direct approach does not rely on the 6Li(n,t)4He cross section or any other nuclear data. The detection efficiency is consistent with the value used in 2005 but was measured with a precision of 0.057 %, which represents a five-fold improvement in the uncertainty. We have verified the temporal stability of the neutron monitor through ancillary measurements, allowing us to apply the measured neutron monitor efficiency to the lifetime result from the 2005 experiment. The updated lifetime is $\tau_n = (887.7 \pm 1.2 [\textrm{stat}] \pm 1.9 [\textrm{syst}])$ s., Comment: v2 - Updated article with revisions made during editorial process, journal citation and DOI added. v1 - Draft article as submitted to Phys. Rev. Lett. (plus a few changes from institution review)

Precision measurements in neutron beta decay serve to determine the coupling constants of beta decay and allow for several stringent tests of the standard model. This paper discusses the design and the expected performance of the Nab spectrometer., Submitted to Proceedings of the Conference CIPANP12, St.Petersburg, Florida, May 2012

The major goal of this project is to determine and compare the overall dynamic architectures of both ERs bound to different known DNA response elements (EREs). This study combines small-angle X-ray solution scattering (SAXS) data and computational modeling to address the multimeric assembly of ER DBD-hinge-LBD complexes. To date, we have successfully modeled ER CDE bound to its cognate DNA binding site and generated homogenous ER DBD-hinge-LDB protein samples (ER CDEF) needed for SAXS studies. We have also collected SAXS data on ER CDEF, but not ER CDE. We will continue to generate and compare the ER CDE and CDEF fragments for small angle x-ray scattering (SAXS) analyses of ER multidomain fragments EREs and various peptides to obtain solution structure information. Having worked out the conditions for the expression and purification of ER CDEF, we do not expect difficulties in the expression and purification of ER CDE domain. By integrating SAXS analyses and computational biology, we expect to better understand ER multi-domain assembly mechanisms. It is anticipated that this information will help explain how domain interfaces in ER/ERE complexes modulate ligand-dependent transcriptional activity in response to various SERMs, providing novel structural insights that will facilitate improved targeting of ER-positive breast cancers, especially those that are refractory to current adjuvant therapies.