Achieving ultra-low and -uniform residual magnetic fields in a very large magnetically shielded room for fundamental physics experiments.

High-precision searches for an electric dipole moment of the neutron (nEDM) require stable and uniform magnetic field environments. We present the recent achievements of degaussing and equilibrating the magnetically shielded room (MSR) for the n2EDM experiment at the Paul Scherrer Institute. We present the final degaussing configuration that will be used for n2EDM after numerous studies. The optimized procedure results in a residual magnetic field that has been reduced by a factor of two. The ultra-low field is achieved with the full magnetic-field-coil system, and a large vacuum vessel installed, both in the MSR. In the inner volume of ∼1.4m3, the field is now more uniform and below 300 pT. In addition, the procedure is faster and dissipates less heat into the magnetic environment, which in turn, reduces its thermal relaxation time from 12h down to 1.5h.

A large 'Active Magnetic Shield' for a high-precision experiment: nEDM collaboration.

We present a novel Active Magnetic Shield (AMS), designed and implemented for the n2EDM experiment at the Paul Scherrer Institute. The experiment will perform a high-sensitivity search for the electric dipole moment of the neutron. Magnetic-field stability and control is of key importance for n2EDM. A large, cubic, 5 m side length, magnetically shielded room (MSR) provides a passive, quasi-static shielding-factor of about 105 for its inner sensitive volume. The AMS consists of a system of eight complex, feedback-controlled compensation coils constructed on an irregular grid spanned on a volume of less than 1000 m3 around the MSR. The AMS is designed to provide a stable and uniform magnetic-field environment around the MSR, while being reasonably compact. The system can compensate static and variable magnetic fields up to ±50µT (homogeneous components) and ±5µT/m (first-order gradients), suppressing them to a few µT in the sub-Hertz frequency range. The presented design concept and implementation of the AMS fulfills the requirements of the n2EDM experiment and can be useful for other applications, where magnetically silent environments are important and spatial constraints inhibit simpler geometrical solutions.

The very large n2EDM magnetically shielded room with an exceptional performance for fundamental physics measurements.

We present the magnetically shielded room (MSR) for the n2EDM experiment at the Paul Scherrer Institute, which features an interior cubic volume with each side of length 2.92 m, thus providing an accessible space of 25 m3. The MSR has 87 openings of diameter up to 220 mm for operating the experimental apparatus inside and an intermediate space between the layers for housing sensitive signal processing electronics. The characterization measurements show a remanent magnetic field in the central 1 m3 below 100 pT and a field below 600 pT in the entire inner volume, up to 4 cm to the walls. The quasi-static shielding factor at 0.01 Hz measured with a sinusoidal 2 µT peak-to-peak signal is about 100 000 in all three spatial directions and increases rapidly with frequency to reach 108 above 1 Hz.

Ultracold neutron storage and transport at the PSI UCN source.

Efficient neutron transport is a key ingredient to the performance of ultracold neutron (UCN) sources, important to meeting the challenges placed by high precision fundamental physics experiments. At the Paul Scherrer Institute's UCN source we have been continuously improving our understanding of the UCN source parameters by performing a series of studies to characterize neutron production and moderation, and UCN production, extraction, and transport efficiency to the beamport. The present study on the absolute UCN transport efficiency completes our previous publications. We report on complementary measurements, namely one on the height-dependent UCN density and a second on the transmission of a calibrated quantity of UCN over a ∼ 16  m long UCN guide section connecting one beamport via the source storage vessel to another beamport. These allow us quantifying and optimizing the performance of the guide system based on extensive Monte Carlo simulations.

The design of the n2EDM experiment: nEDM Collaboration.

We present the design of a next-generation experiment, n2EDM, currently under construction at the ultracold neutron source at the Paul Scherrer Institute (PSI) with the aim of carrying out a high-precision search for an electric dipole moment of the neutron. The project builds on experience gained with the previous apparatus operated at PSI until 2017, and is expected to deliver an order of magnitude better sensitivity with provision for further substantial improvements. An overview is of the experimental method and setup is given, the sensitivity requirements for the apparatus are derived, and its technical design is described.

Data blinding for the nEDM experiment at PSI.

Psychological bias towards, or away from, prior measurements or theory predictions is an intrinsic threat to any data analysis. While various methods can be used to try to avoid such a bias, e.g. actively avoiding looking at the result, only data blinding is a traceable and trustworthy method that can circumvent the bias and convince a public audience that there is not even an accidental psychological bias. Data blinding is nowadays a standard practice in particle physics, but it is particularly difficult for experiments searching for the neutron electric dipole moment (nEDM), as several cross measurements, in particular of the magnetic field, create a self-consistent network into which it is hard to inject a false signal. We present an algorithm that modifies the data without influencing the experiment. Results of an automated analysis of the data are used to change the recorded spin state of a few neutrons within each measurement cycle. The flexible algorithm may be applied twice (or more) to the data, thus providing the option of sequentially applying various blinding offsets for separate analysis steps with independent teams. The subtle manner in which the data are modified allows one subsequently to adjust the algorithm and to produce a re-blinded data set without revealing the initial blinding offset. The method was designed for the 2015/2016 measurement campaign of the nEDM experiment at the Paul Scherrer Institute. However, it can be re-used with minor modification for the follow-up experiment n2EDM, and may be suitable for comparable projects elsewhere.

Mutation-Simulator: fine-grained simulation of random mutations in any genome.

SUMMARY: Mutation-Simulator allows the introduction of various types of sequence alterations in reference sequences, with reasonable compute-time even for large eukaryotic genomes. Its intuitive system for fine-grained control over mutation rates along the sequence enables the mimicking of natural mutation patterns. Using standard file formats for input and output data, it can easily be integrated into any development and benchmarking workflow for high-throughput sequencing applications. AVAILABILITY AND IMPLEMENTATION: Mutation-Simulator is written in Python 3 and the source code, documentation, help and use cases are available on the Github page at https://github.com/mkpython3/Mutation-Simulator. It is free for use under the GPL 3 license.

Crop wild relative populations of Beta vulgaris allow direct mapping of agronomically important genes.

Rapid identification of agronomically important genes is of pivotal interest for crop breeding. One source of such genes are crop wild relative (CWR) populations. Here we used a CWR population of <200 wild beets (B. vulgaris ssp. maritima), sampled in their natural habitat, to identify the sugar beet (Beta vulgaris ssp. vulgaris) resistance gene Rz2 with a modified version of mapping-by-sequencing (MBS). For that, we generated a draft genome sequence of the wild beet. Our results show the importance of preserving CWR in situ and demonstrate the great potential of CWR for rapid discovery of causal genes relevant for crop improvement. The candidate gene for Rz2 was identified by MBS and subsequently corroborated via RNA interference (RNAi). Rz2 encodes a CC-NB-LRR protein. Access to the DNA sequence of Rz2 opens the path to improvement of resistance towards rhizomania not only by marker-assisted breeding but also by genome editing.

Observation of Gravitationally Induced Vertical Striation of Polarized Ultracold Neutrons by Spin-Echo Spectroscopy.

We describe a spin-echo method for ultracold neutrons (UCNs) confined in a precession chamber and exposed to a |B0|=1 µT magnetic field. We have demonstrated that the analysis of UCN spin-echo resonance signals in combination with knowledge of the ambient magnetic field provides an excellent method by which to reconstruct the energy spectrum of a confined ensemble of neutrons. The method takes advantage of the relative dephasing of spins arising from a gravitationally induced striation of stored UCNs of different energies, and also permits an improved determination of the vertical magnetic-field gradient with an exceptional accuracy of 1.1 pT/cm. This novel combination of a well-known nuclear resonance method and gravitationally induced vertical striation is unique in the realm of nuclear and particle physics and should prove to be invaluable for the assessment of systematic effects in precision experiments such as searches for an electric dipole moment of the neutron or the measurement of the neutron lifetime.

Highly stable atomic vector magnetometer based on free spin precession.

We present a magnetometer based on optically pumped Cs atoms that measures the magnitude and direction of a 1 µT magnetic field. Multiple circularly polarized laser beams were used to probe the free spin precession of the Cs atoms. The design was optimized for long-time stability and achieves a scalar resolution better than 300 fT for integration times ranging from 80 ms to 1000 s. The best scalar resolution of less than 80 fT was reached with integration times of 1.6 to 6 s. We were able to measure the magnetic field direction with a resolution better than 10 µrad for integration times from 10 s up to 2000 s.

Duration discrimination and subjective duration for ramped and damped sounds.

The perception of stimuli with ramped envelopes (gradual attack and abrupt decay) and damped envelopes (abrupt attack and gradual decay) was studied in subjective and objective tasks. Magnitude estimation (ME) of perceived duration was measured for broadband noise, 1.0-kHz, and 8.0-kHz tones for durations between 10 and 200 ms. Damped sounds were judged to be shorter than ramped sounds. Matching experiments between sounds with ramped, damped, and rectangular envelopes also showed that damped sounds are perceived to be shorter than ramped sounds, and, additionally, the reason for the effect is a result of the damped sound being judged shorter than a rectangular-gated sound rather than the ramped sound being judged longer than a rectangular-gated sound. These matching studies also demonstrate that the size of the effect is larger for tones (factor of 2.0) than for broadband noise (factor of 1.5). There are two plausible explanations for the finding that damped sounds are judged to be shorter than ramped or rectangular-gated sounds: (1) the abrupt offset at a high level of the ramped sound (or a rectangular-gated sound) results in a persistence of perception (forward masking) that is considered in judgments of the subjective duration; and (2) listeners may ignore a portion of the decay of a damped sound because they consider it an "echo" [Stecker and Hafter, J. Acoust. Soc. Am. 107, 3358-3368 (2000)]. In another experiment, duration discrimination for broadband noise with ramped, damped, and rectangular envelopes was studied as a function of duration (10 to 100 ms) to determine if differences in perceived duration are associated with the size of measured Weber fractions. A forced-choice adaptive procedure was used. Duration discrimination was poorer for noise with ramped envelopes than for noise with damped or rectangular envelopes. This result is inconsistent with differences in perceived duration and no explanation was readily apparent.

Safety and clinical performance of acoustic reflex tests.

OBJECTIVE: Safety and effectiveness of acoustic reflex tests are important issues because these tests are widely applied to screen for retrocochlear pathology. Previous studies have reported moderately high sensitivity and specificity for detection of acoustic neuroma. However, there have been reports of possible iatrogenic hearing loss resulting from acoustic reflex threshold (ART) and decay (ARD) tests. This study assessed safety and clinical performance of ART tests for detection of acoustic neuroma. DESIGN: We report a case in which ARD testing resulted in a significant bilateral permanent threshold shift. This case was the impetus for us to investigate the clinical utility of ART and ARD tests. We analyzed sensitivity and specificity of ART, as well as asymmetry in pure-tone thresholds (PTT) for detection of acoustic neuroma in 56 tumor and 108 non-tumor ears. RESULTS AND CONCLUSIONS: Sensitivity and specificity were higher for PTT asymmetry than for ART. Ipsilateral ART at 1000 Hz had poor sensitivity and specificity for detection of acoustic neuroma, and involves some potential risk to residual hearing for presentation levels higher than 115 dB SPL. Approximately half of the acoustic neuroma group had ipsilateral ARTs that would require administration of ARD tests at levels exceeding 115 dB SPL. Therefore, we conclude that PTT asymmetry is a more effective test for detection of acoustic neuroma, and involves no risk to residual hearing. Future studies of contralateral reflex threshold and ARD in combination with PTT asymmetry are recommended.

Histamine alters cadherin-mediated sites of endothelial adhesion.

We tested the hypothesis that histamine alters the focal apposition of endothelial cells by acting on sites of cadherin-mediated cell-cell adhesion. Focal apposition was measured as the impedance of a cell-covered electrode, which was partitioned into a cell-matrix resistance, a cell-cell resistance, and membrane capacitance. Histamine causes an immediate, short-lived decrease in the impedance of an electrode covered with human umbilical vein endothelial (HUVE) cells. ECV304 cells are a line of spontaneously transformed HUVE cells that do not express the endothelial cadherin, cadherin-5. Histamine increased ECV304 cell calcium to 600 nM. Histamine did not increase myosin light chain phosphorylation of control or transfected ECV304 cells. ECV304 cells transfected with either E-cadherin or cadherin-5 on a dexamethasone-responsive plasmid (pLKneo) increased their cell-cell resistance when stimulated with dexamethasone, whereas ECV304 cells transfected with pLKneo-lacZ did not. Histamine did not affect the impedance of ECV304 cells transfected with pLKneo-lacZ. In contrast, histamine decreased the cell-cell resistance of ECV304 cells transfected with either pLKneo-E-cadherin or pLKneo-cadherin-5. From these data, we conclude that histamine acts on sites of cadherin-mediated cell-cell apposition.

The peaked audiometric configuration in Meniere's disease: disease related?

A retrospective analysis of audiograms was completed for persons from 3 different patient groups. These 3 groups were (1) persons with unilateral Meniere's disease, (2) persons with unilateral acoustic tumor, and (3) persons from the general clinical population of an audiology clinic in a major medical center. As Paparella, McDermott, Luiz, and de Sousa (1982) also report, the most common audiometric configuration in the Meniere's disease group was peaked, a condition in which poorer hearing is reported in the low and high frequencies, and an island of better hearing sensitivity occurs at either 1.0 or 2.0 kHz. Some of the peaked audiograms from persons in our Meniere's disease group could be a result of a low-frequency hearing loss caused by Meniere's disease combined with a high-frequency hearing loss due to aging or other environmental factors. However, 27% (13/48) of the peaked audiograms in ears with Meniere's disease were found in persons with no hearing loss in the high frequencies of their nondiseased ear. Thus, the peaked audiometric configuration is associated with Meniere's disease, as suggested by research results from animals with experimentally induced endolymphatic hydrops. Peaked audiometric configurations were also observed in roughly 9% of the general clinical population and in 12.5% of ears of persons with acoustic tumors. A rule--based on the audiometric configurations that maximized identification of patients with Meniere's disease--using the general clinical population as a control did not fare as well when the tumor group was used as a control. This finding provides further evidence that peaked audiograms, although common to Meniere's disease, are not pathognomonic of this disease. Furthermore, these results indicate that the diagnosis of Meniere's disease from audiometric profiles is risky, at best.

Masker laterality and cueing in forward-masked intensity discrimination.

Forward-masked intensity discrimination was measured as a function of level in experiments designed to reveal insights into the mechanism(s) underlying the midlevel elevation of the Weber fraction. The standard and maskers were 1.0-kHz tones that were separated by 100 ms. Performance was measured for listeners with normal hearing using an adaptive procedure. In experiment 1, intensity discrimination was measured in the presence of an ipsilateral masker (80 dB SPL), a contralateral masker (93 dB SPL), and a binaural (dichotic) masker produced by combining the ipsilateral and contralateral maskers. Listeners perceived only the contralateral masker in the binaural-masker condition. The contralateral masker produced a small midlevel elevation of the Weber fraction. The ipsilateral masker and the binaural masker produced a large, midlevel elevation of the Weber fraction. Experiment 2 found that a two-tone masker resulted in a reduction (improvement) in the Weber fraction for some conditions, but the midlevel elevation remained for all subjects in this cue-tone condition. Experiment 3 demonstrated that cross talk could not account for all of the masking observed with contralateral maskers. Taken together, the results suggest that a single complex mechanism or multiple mechanisms may be responsible for the masking seen in these experiments. On the basis of the cueing results, it is concluded that a portion of the masking is due to cognitive factors; however, a sensory mechanism cannot be ruled out for the remaining portion, based on the results of these experiments. Finally, a small but significant amount of masking due to contralateral maskers places the mechanism for this outcome central to the cochlear nucleus.

Basilar membrane nonlinearity and loudness.

Loudness matching functions for tones for persons with one shifted-threshold ear (hearing loss and noise-shifted thresholds) and one ear within normal limits were used to derive the presumed basilar membrane (BM) input-output (I/O) function in a normal ear. The comparison was made by assuming that the BM I/O function for the ear with the cochlear threshold shift has a slope of one (a linearized cochlea). The function for the normal ear was derived from the loudness matching function based on this assumption. Comparisons were made for archival basilar membrane data [M. A. Ruggero, N. C. Rich, A. Recio, S. S. Narayan, and L. Robles, J. Acoust. Soc. Am. 101, 2151-2163 (1997)] for chinchilla and archival loudness matches for long-duration tones for persons with various degrees of cochlear hearing loss [F. Miskolczy-Fodor, J. Acoust Soc. Am. 32, 486-492 (1960)]. Comparisons were made also between BM I/O functions and ones derived from loudness matches for persons with unilateral hearing loss simulated by broadband noise. The results show a close resemblance between the basilar membrane I/O function and the function derived from loudness matches for long-duration tones, even though the comparison was between human and chinchilla data. As the degree of threshold shift increases from 40 to 80 dB, the derived BM I/O functions become shallower, with slopes for losses of 60 dB or more falling in the range of values reported for physiological data. Additional measures with short-duration tones in noise show that the slope of the loudness function and the slope of the derived basilar membrane I/O function are associated with the behavioral threshold for the tone. The results for long-duration tones suggest a correspondence between BM displacement and loudness perception in cases of recruitment, but the relation between the degree of loss and the amount of BM compression and the relation between signal duration and compression suggests that other factors, such as the neural population response, may play a role.

Thrombin inhibits myosin light chain dephosphorylation in endothelial cells.

Histamine and thrombin increase myosin light-chain kinase-mediated phosphorylation of myosin light chain (MLC) in human umbilical vein endothelial cells (HUVEC). The increase in MLC phosphorylation caused by thrombin persists longer (330 min) than the increase caused by histamine (<5 min), although both increase cell calcium similarly. We hypothesized that some of the longer duration of the increase in MLC phosphorylation caused by thrombin was because of inhibition of myosin dephosphorylation by thrombin. Calyculin A, an inhibitor of type 1 and 2A protein phosphatases, caused a time-dependent increase in MLC phosphorylation in unstimulated HUVEC. As thrombin-stimulated phosphorylation approached its peak at 15 min, calyculin A caused progressively less of an increase in MLC phosphorylation in thrombin-stimulated HUVEC, and no increase at the peak of thrombin stimulation. In HUVEC in which cell calcium was maintained at 600 nM, thrombin increased MLC phosphorylation above the level caused by increased calcium alone at a time coinciding with the peak of thrombin stimulation. However, when phosphatase activity was already inhibited with calyculin A, thrombin did not further increase MLC phosphorylation in cells in which calcium was maintained at 600 nM calcium. Thrombin increases MLC phosphorylation in HUVEC not only by increasing cell calcium but also by inhibiting calyculin A-sensitive dephosphorylation of MLC.

[External humeral fixation in war injuries].

Type III open fractures of the humerus caused by high energy missiles or shrapnel in 26 male soldiers were treated by external fixation. 12 suffered from associated injuries involving the head and chest, 12 had 14 nerve injuries, and 4 required simultaneous repair of the brachial artery. Results in 19 examined after an average of 6.5 years were excellent in 22%, good in 52%, fair in 16%, and poor in 10%. The aim of external fixation is functional limb salvage. We think high-energy gunshot fractures should be classified as III-d because of the severe damage to the soft tissue, which differs from that of low-velocity, gunshot fractures or farm injuries. We conclude that external fixation is the preferred form of primary stabilization of severe open fractures of the humerus. It has reduced the incidence of chronic infection and has improved the prognosis of vascular repairs. The treatment of the soft tissues, skin coverage, and ultimately reconstructive surgery are facilitated. Early limb function allows for a better final result. For delayed union and pin-tract infection a different definitive method, such as internal fixation or a plaster case, is required.