Search for Neutron-to-Hidden-Neutron Oscillations in an Ultracold Neutron Beam.

Models that postulate the existence of hidden sectors address contemporary questions, such as the source of baryogenesis and the nature of dark matter. Neutron-to-hidden-neutron oscillations are among the possible mixing processes and have been tested with ultracold neutron storage and passing-through-wall experiments to set constraints on the oscillation period τ_{nn^{'}}. These searches probe the oscillations as a function of the mass splitting due to the neutron-hidden-neutron energy degeneracy. In this work, we present a new limit derived from neutron disappearance in ultracold neutron beam experiments. The overall limit, given by τ_{nn^{'}}>1 s for |δm|∈[2,69] peV(95.45% C.L.), covers the yet unexplored intermediate mass-splitting range and contributes to the ongoing research on hidden sectors.

Final Results of GERDA on the Two-Neutrino Double-ß Decay Half-Life of

We present the measurement of the two-neutrino double-ß decay rate of ^{76}Ge performed with the GERDA Phase II experiment. With a subset of the entire GERDA exposure, 11.8 kg yr, the half-life of the process has been determined: T_{1/2}^{2ν}=(2.022±0.018_{stat}±0.038_{syst})×10^{21} yr. This is the most precise determination of the ^{76}Ge two-neutrino double-ß decay half-life and one of the most precise measurements of a double-ß decay process. The relevant nuclear matrix element can be extracted: M_{eff}^{2ν}=(0.101±0.001).

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.

Measurement of the Permanent Electric Dipole Moment of the Neutron.

We present the result of an experiment to measure the electric dipole moment (EDM) of the neutron at the Paul Scherrer Institute using Ramsey's method of separated oscillating magnetic fields with ultracold neutrons. Our measurement stands in the long history of EDM experiments probing physics violating time-reversal invariance. The salient features of this experiment were the use of a ^{199}Hg comagnetometer and an array of optically pumped cesium vapor magnetometers to cancel and correct for magnetic-field changes. The statistical analysis was performed on blinded datasets by two separate groups, while the estimation of systematic effects profited from an unprecedented knowledge of the magnetic field. The measured value of the neutron EDM is d_{n}=(0.0±1.1_{stat}±0.2_{sys})×10^{-26} e.cm.

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.

Search for tri-nucleon decays of 76Ge in GERDA.

We search for tri-nucleon decays of 76Ge in the dataset from the GERmanium Detector Array (GERDA) experiment. Decays that populate excited levels of the daughter nucleus above the threshold for particle emission lead to disintegration and are not considered. The ppp-, ppn-, and pnn-decays lead to 73Cu, 73Zn, and 73Ga nuclei, respectively. These nuclei are unstable and eventually proceed by the beta decay of 73Ga to 73Ge (stable). We search for the 73Ga decay exploiting the fact that it dominantly populates the 66.7 keV 73mGa state with half-life of 0.5 s. The nnn-decays of 76Ge that proceed via 73mGe are also included in our analysis. We find no signal candidate and place a limit on the sum of the decay widths of the inclusive tri-nucleon decays that corresponds to a lower lifetime limit of 1.2×1026 yr  (90% credible interval). This result improves previous limits for tri-nucleon decays by one to three orders of magnitude.

Liquid argon light collection and veto modeling in GERDA Phase II.

The ability to detect liquid argon scintillation light from within a densely packed high-purity germanium detector array allowed the Gerda experiment to reach an exceptionally low background rate in the search for neutrinoless double beta decay of 76 Ge. Proper modeling of the light propagation throughout the experimental setup, from any origin in the liquid argon volume to its eventual detection by the novel light read-out system, provides insight into the rejection capability and is a necessary ingredient to obtain robust background predictions. In this paper, we present a model of the Gerda liquid argon veto, as obtained by Monte Carlo simulations and constrained by calibration data, and highlight its application for background decomposition.

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.

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.

Cardiovascular and renal action of platelet-activating factor in anesthetized dogs.

Platelet-activating factor (PAF) has hypotensive effects similar to those of antihypertensive polar renomedullary lipid (APRL), a potent endogenous hypotensive lipid. In this study the cardiovascular and renal effects of PAF were characterized in anesthetized dogs. Intravenous infusion of PAF at 0.1 micrograms/kg/min for 1 hour caused marked reduction in arterial blood pressure and cardiac output and was accompanied by minimal changes in heart rate. Concomitantly, renal blood flow, glomerular filtration rate, urine flow, and fractional excretion of Na+ and K+ fell significantly. Plasma renin activity was greatly stimulated (11.9 +/- 1.66 vs 3.26 +/- 0.45 ng/angiotensin I/ml/hr for the placebo group). There were no significant alterations in any of these parameters following PAF at a lower dose (0.03 micrograms/kg/min for 1 hour). In a separate study, PAF at 0.1 micrograms/kg/min for 20 minutes produced a decrease in left ventricular myocardial contractile force, concomitant with bradycardia and hypotension, which indicated the presence of a negative inotropic activity. It is concluded that systemic administration of PAF has a deleterious effect on kidney function due to arterial hypotension and diminished cardiac output.

Atrial natriuretic factor-potentiating and antihypertensive activity of SCH 34826. An orally active neutral metalloendopeptidase inhibitor.

The effects of SCH 34826, an orally active neutral metalloendopeptidase inhibitor, on responses to atrial natriuretic factor-(103-125) or -(99-126) and on blood pressure were evaluated in rats. SCH 34826 (10, 30, and 90 mg/kg s.c. and 90 mg/kg p.o.) potentiated the antihypertensive action of atrial natriuretic factor (30 micrograms/kg i.v.) in conscious spontaneously hypertensive rats. SCH 34826 (90 mg/kg) also potentiated the diuretic and natriuretic responses to atrial natriuretic factor (30 micrograms/kg i.v.) as well as the plasma levels achieved after peptide injection. SCH 34826 significantly reduced blood pressure in the conscious deoxycorticosterone acetate-salt hypertensive rat, at doses of 90 mg/kg s.c. (-35 +/- 12 mm Hg), 10 mg/kg p.o. (-30 +/- 7 mm Hg), and 90 mg/kg p.o. (-45 +/- 6 mm Hg). SCH 34826 was devoid of acute antihypertensive activity in the spontaneously hypertensive rat but reduced blood pressure by day 3 of a 5-day treatment schedule. SCH 34826 (90 mg/kg s.c.) enhanced urine volume output in the deoxycorticosterone acetate-salt rat (2.78 +/- 0.6 vs. 1.27 +/- 0.3 ml/100 g/3 hr in vehicle-control rats, p less than 0.05). SCH 34826 (90 mg/kg s.c.) increased plasma levels of atrial natriuretic factor at 1 hour (753 +/- 89 vs. 451 +/- 79 pg/ml in vehicle-treated rats, p less than 0.05) but not 3 hours after dosing. The renal excretion of atrial natriuretic factor (3,092 +/- 1,089 vs. 21 +/- 6 pg/100 g/3 hr in vehicle-treated rats, p less than 0.05) and cyclic guanosine monophosphate (2,131 +/- 509 vs. 879 +/- 168 pg/100 g/3 hr in vehicle-treated rats, p less than 0.05) was markedly elevated by SCH 34826 in deoxycorticosterone acetate-salt rats. These studies suggest that neutral endopeptidase inhibition may represent a new approach to treatment of some forms of hypertension.

Antiulcer agents. 3. Structure-activity-toxicity relationships of substituted imidazo[1,2-a]pyridines and a related imidazo[1,2-a]pyrazine.

Investigation of the interrelationship between structure, antiulcer activity, and toxicology screening data derived from a series of compounds selected from structure-activity studies directed toward identifying a successor to 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1), has identified 3-(cyanomethyl)-2,7-dimethyl-8-(phenylmethoxy)imidazo[1,2 -a]pyridine (5), 3-amino-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine (6), and 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine (7). These analogues exhibit a combination of antisecretory and cytoprotective activity in animal models, while eliminating the adverse effects of the prototype 1. One of these, 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine, Sch 32651 (7), has a profile meeting all criteria.

Antiinflammatory activity of a series of substituted 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-diones.

A series of substituted analogues based on the novel 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-dione ring system have been synthesized and shown to exhibit antiinflammatory activity in the adjuvant-induced arthritis rat model (AAR). The activity exhibited by the pyrimidopurinediones in this model of chronic inflammation is comparable to that of their previously studied 2-oxo congeners, the 6-hydroxypyrimido[2,1-f]purine-2,4,8-(1H,3H,9H)-triones, the best of which show potency levels approximately equal to that of naproxen. On the basis of its potency in the AAR assay, 9-benzyl-2,3-dihydro-1,3-dimethyl-6-hydroxy-7-(3-methyl-2-butenyl) pyrimido-[2,1-f]purine-4,8(1H,9H)-dione was selected for further evaluation and found to exhibit cyclooxygenase inhibitory activity in the in vitro rat neutrophil model. With respect to side-effect liability, this prenylated derivative has been shown to be devoid of gastric ulcer inducing potential, as well as the ocular toxicity observed previously with the 2-oxo series.

Antiinflammatory activity of substituted 6-hydroxypyrimido[2,1-f]purine-2,4,8(1H,3H,9H)-triones. Atypical nonsteroidal antiinflammatory agents.

A novel class of antiinflammatory drugs, which are substituted derivatives of the fused tricyclic system 6-hydroxypyrimido[2,1-f]purine-2,4,8(1H,3H,9H)-trione, is described. Synthetic procedures and structure determination with the assistance of X-ray crystallography are discussed. Semiempirical molecular orbital calculations are used to investigate the relative stability of the possible isomers and tautomers of the title compounds. A biological profile of the class, and of several of the more potent analogues, in several antiinflammatory models, including the adjuvant-induced arthritis and the collagen II models, is defined. Several members of the class are shown to possess extremely low ulcerogenic effects in spite of exhibiting cyclooxygenase inhibition. A preliminary bioavailability study of two of the lead structures is presented. The compounds 6-72 appear to constitute a class of drugs that shows interesting potential antiarthritic activity and also exhibits an activity profile different from that of the standard classical NSAI drugs, as determined by a comparison of the profile of this class of drug with that of several standard agents. Certain findings from toxicological studies have precluded the further development of compounds within this group, although related structural types are being investigated.

Synthesis and pharmacological activity of angiotensin converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines.

The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.

Antiulcer agents. 4. Conformational considerations and the antiulcer activity of substituted imidazo[1,2-a]pyridines and related analogues.

Definition of the interrelationship between the conformational characteristics of a series of substituted imidazo[1,2-a]pyridines and their antiulcer activity was investigated by examining the conformational properties of 3-cyano-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine (1), using a variety of experimental and theoretical methods. The results of these studies was the identification of two distinctly different candidates, designated the "folded" and the "extended" conformation, respectively, to represent the two possible minimum-energy conformations of 1. In order to select the biologically relevant conformer, a group of 3-substituted 2-methylimidazo[1,2-a]pyridines, having either a cis or a trans 2-phenylethenyl substituent at the 8-position were designed as conceptually simple and synthetically accessible semirigid analogues of the respective candidate conformers. Gastric antisecretory activity was found to reside only in the trans isomers (compounds 11, 15, and 17), which mimic the "extended" conformation. This observation led to the construction of 8,9-dihydro-2-methyl-9-phenyl-7H-imidazo[1,2-a]pyrano[2,3-c]pyridi ne-3- acetonitrile (40), a rigid tricyclic analogue that is effectively locked in the "extended" conformation and that exhibited an antiulcer profile comparable to that of prototype 1. These results unequivocally demonstrate that, in accord with expectation for a drug operating at a specific receptor, the conformational characteristics of the molecule have a substantial effect in determining its antiulcer activity. More precisely, it has been demonstrated that it is the "extended" conformation of 1 that represents the "bioactive" form of the drug. These results constitute the basis for a molecular probe that should aid in the investigation of the as yet uncharacterized gastric proton pump enzyme (H+/K+-ATPase), by means of which 1 and its analogues presumably exert their pharmacologic actions.

Effects of SCH 32651 on resting and stimulated acid secretion in guinea-pig isolated fundic mucosa.

Effects of SCH 32651, a novel antisecretory and cytoprotective agent, on resting and stimulated acid secretion by the guinea-pig isolated fundic mucosa were studied. SCH 32651 inhibited resting acid secretion in proportion to concentrations in serosal solution (0.1-10 microM), the IC50 being 4.4 microM. Cimetidine and atropine at concentrations up to 100 microM were inactive. Serosal application of SCH 32651 inhibited acid secretory responses to histamine (10 microM), methacholine (1 microM) or dibutyryl cyclic AMP (0.5 mM) plus theophylline (1 mM) in a concentration-dependent manner. The IC50S against histamine, methacholine and db cyclic AMP plus theophylline were 4.2 microM, 0.71 microM and 2.9 microM, respectively. In contrast, atropine and cimetidine each at 100 microM, a concentration that entirely abolished responses to methacholine and histamine, respectively, did not affect acid responses to db cyclic AMP plus theophylline. The inhibitory effects of SCH 32651 on resting and histamine-stimulated acid secretion were readily reversible upon washing. SCH 32651 0.1 mM in the mucosal solution also greatly suppressed the resting and stimulated acid secretion. In the presence of histamine treatment, SCH 32651 concomitantly caused a marked rise in K+ entry into the mucosal solution in parallel to a decline in the appearance of H+ in the same solution. The various events demonstrated by SCH 32651 in the present study are shared by omeprazole, a potent antisecretory agent working through inhibition of gastric H+/K+-ATPase. We conclude that SCH 32651 as a potent antisecretory agent seems to act directly on the parietal cell, near or at the site of H+/K+-ATPase which is a final step in the acid secretory process triggered by various stimuli.

Augmentation of leukotriene C4 and D4 release due to severe stenosis in the canine coronary artery stimulated by the calcium ionophore A23187.

In dogs undergoing 24- or 72-hr severe narrowing of the left anterior descending coronary artery (LAD), the in vitro formation of immunoreactive leukotriene C4 (LTC4) by the stenosed LAD was greatly augmented by 1 microM A23187 in a 10-min incubation at 37 degrees. This stimulated LTC4 formation was abolished by 30 microM nordihydroguaiaretic acid (NDGA). The incubation products were identified by high performance liquid chromatography and radioimmunoassay to be largely composed of LTC4 and LTD4 in similar proportion. In contrast to the stenosed LAD, the non-stenotic left circumflex coronary artery, apex of the heart, and renal artery of the same experimental animals failed to respond to the calcium ionophore up to 10 microM. The vascular and cardiac tissues from sham-operated animals also remained quiescent in the presence of A23187. The normal coronary artery showed low levels of leukotriene formation and was resistant to the ionophore. It is proposed that a latent portion of leukotriene synthesis, which can be triggered by the calcium ionophore, may play a significant role in the pathogenesis of coronary artery spasm associated with acute myocardial infarction and angina pectoris in patients with obstructive coronary artery disease.