Search for a Neutron Dark Decay in

Neutron dark decays have been suggested as a solution to the discrepancy between bottle and beam experiments, providing a dark matter candidate that can be searched for in halo nuclei. The free neutron in the final state following the decay of ^{6}He into ^{4}He+n+χ provides an exceptionally clean detection signature when combined with a high efficiency neutron detector. Using a high-intensity ^{6}He^{+} beam at Grand Accélérateur National d'Ions Lourds, a search for a coincident neutron signal resulted in an upper limit on a dark decay branching ratio of Br_{χ}≤4.0×10^{-10} (95% C.L.). Using the dark neutron decay model proposed originally by Fornal and Grinstein, we translate this into an upper bound on a dark neutron branching ratio of O(10^{-5}), improving over global constraints by one to several orders of magnitude depending on m_{χ}.

High-Precision Spectroscopy of

The excited states of unstable ^{20}O were investigated via γ-ray spectroscopy following the ^{19}O(d,p)^{20}O reaction at 8 AMeV. By exploiting the Doppler shift attenuation method, the lifetimes of the 2_{2}^{+} and 3_{1}^{+} states were firmly established. From the γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2_{2}^{+} and 3_{1}^{+} states, the B(E2) and B(M1) were determined. Various chiral effective field theory Hamiltonians, describing the nuclear properties beyond ground states, along with a standard USDB interaction, were compared with the experimentally obtained data. Such a comparison for a large set of γ-ray transition probabilities with the valence space in medium similarity renormalization group ab initio calculations was performed for the first time in a nucleus far from stability. It was shown that the ab initio approaches using chiral effective field theory forces are challenged by detailed high-precision spectroscopic properties of nuclei. The reduced transition probabilities were found to be a very constraining test of the performance of the ab initio models.

Neuromodulation using ultra low frequency current waveform reversibly blocks axonal conduction and chronic pain.

Chronic pain remains a leading cause of disability worldwide, and there is still a clinical reliance on opioids despite the medical side effects associated with their use and societal impacts associated with their abuse. An alternative approach is the use of electrical neuromodulation to produce analgesia. Direct current can block action potential propagation but leads to tissue damage if maintained. We have developed a form of ultra low frequency (ULF) biphasic current and studied its effects. In anesthetized rats, this waveform produced a rapidly developing and completely reversible conduction block in >85% of spinal sensory nerve fibers excited by peripheral stimulation. Sustained ULF currents at lower amplitudes led to a slower onset but reversible conduction block. Similar changes were seen in an animal model of neuropathic pain, where ULF waveforms blocked sensory neuron ectopic activity, known to be an important driver of clinical neuropathic pain. Using a computational model, we showed that prolonged ULF currents could induce accumulation of extracellular potassium, accounting for the slowly developing block observed in rats. Last, we tested the analgesic effects of epidural ULF currents in 20 subjects with chronic leg and back pain. Pain ratings improved by 90% after 2 weeks. One week after explanting the electrodes, pain ratings reverted to 72% of pretreatment screening value. We conclude that epidural spinal ULF neuromodulation represents a promising therapy for treating chronic pain.

Counted cycles method to measure the block inception time of kiloHertz frequency mammalian motor nerve block.

BACKGROUND: Kilohertz frequency alternating currents (KHFAC) produce rapid nerve conduction block of mammalian peripheral nerves and have potential clinical applications in reducing nerve hyperactivity. However, there are no experimental measurements of the block inception time (BIT) for the complete block of mammalian motor axons, i.e. the time from the start of delivery of the KHFAC to the axons reaching a fully blocked state. NEW METHOD: A "counted cycles" method (CCM) was designed to exploit characteristics of the onset response, which is typical of KHFAC block, to measure the BIT with a millisecond time resolution. Randomized and repeated experiments were conducted in an in-vivo rodent model, using trains of KHFAC over a range of complete cycle counts at three frequencies (10, 20, and 40 kHz). RESULTS: Complete motor nerve conduction block was obtained in the rat sciatic nerve (N = 4) with an average BIT range of 5 ms-10 ms. The fastest BIT measured was 2.5 ms-5 ms. There was no statistical difference between the block inception times for the three frequencies tested. COMPARISON WITH EXISTING METHODS: There are no comparable methods to measure the KHFAC BIT. CONCLUSION: The KHFAC BIT is faster than previously estimated. KHFAC motor nerve block is established in milliseconds. These results may assist in the design of methods to eliminate the onset response produced by KHFAC nerve block.

First Direct Measurement of Isotopic Fission-Fragment Yields of

A direct and complete measurement of isotopic fission-fragment yields of ^{239}U has been performed for the first time. The ^{239}U fissioning system was produced with an average excitation energy of 8.3 MeV in one-neutron transfer reactions between a ^{238}U beam and a ^{9}Be target at Coulomb barrier energies. The fission fragments were detected and isotopically identified using the VAMOS++ spectrometer at the GANIL facility. The measurement allows us to directly evaluate the fission models at excitation energies of fast neutrons, which are relevant for next-generation nuclear reactors. The present data, in agreement with model calculations, do not support the recently reported anomaly in the fission-fragment yields of ^{239}U, and they confirm the persistence of spherical shell effects in the Sn region at excitation energies exceeding the fission barrier by a few mega-electron volts.

Reduction of the onset response in kilohertz frequency alternating current nerve block with amplitude ramps from non-zero amplitudes.

BACKGROUND: Kilohertz frequency alternating current (KHFAC) waveforms reversibly block conduction in mammalian peripheral nerves. The initiation of the KHFAC produces nerve activation, called the onset response, before complete block occurs. An amplitude ramp, starting from zero amplitude, is ineffective in eliminating this onset activity. We postulated that initiating the ramp from a non-zero amplitude would produce a different effect on the onset. METHODS: Experiments were conducted in an in vivo rat model. KHFAC was applied at supra block threshold amplitudes and then reduced to a lower sub block amplitude (25, 50, 75 and 90% of the block threshold amplitude). The amplitude was then increased again to the original supra block threshold amplitude with an amplitude ramp. This ramp time was varied for each of the amplitude levels tested. RESULTS: The amplitude ramp was successful in eliminating a second onset. This was always possible for the ramps up from 75 and 90% block threshold amplitude, usually from 50% but never from 25% of the block threshold amplitude. CONCLUSIONS: This maneuver can potentially be used to initiate complete nerve block, transition to partial block and then resume complete block without producing further onset responses.

Precision Measurement of the First Ionization Potential of Nobelium.

One of the most important atomic properties governing an element's chemical behavior is the energy required to remove its least-bound electron, referred to as the first ionization potential. For the heaviest elements, this fundamental quantity is strongly influenced by relativistic effects which lead to unique chemical properties. Laser spectroscopy on an atom-at-a-time scale was developed and applied to probe the optical spectrum of neutral nobelium near the ionization threshold. The first ionization potential of nobelium is determined here with a very high precision from the convergence of measured Rydberg series to be 6.626 21±0.000 05 eV. This work provides a stringent benchmark for state-of-the-art many-body atomic modeling that considers relativistic and quantum electrodynamic effects and paves the way for high-precision measurements of atomic properties of elements only available from heavy-ion accelerator facilities.

Probing Sizes and Shapes of Nobelium Isotopes by Laser Spectroscopy.

Until recently, ground-state nuclear moments of the heaviest nuclei could only be inferred from nuclear spectroscopy, where model assumptions are required. Laser spectroscopy in combination with modern atomic structure calculations is now able to probe these moments directly, in a comprehensive and nuclear-model-independent way. Here we report on unique access to the differential mean-square charge radii of ^{252,253,254}No, and therefore to changes in nuclear size and shape. State-of-the-art nuclear density functional calculations describe well the changes in nuclear charge radii in the region of the heavy actinides, indicating an appreciable central depression in the deformed proton density distribution in ^{252,254}No isotopes. Finally, the hyperfine splitting of ^{253}No was evaluated, enabling a complementary measure of its (quadrupole) deformation, as well as an insight into the neutron single-particle wave function via the nuclear spin and magnetic moment.

Copeptin and insulin resistance: effect modification by age and 11 ß-HSD2 activity in a population-based study.

PURPOSE: Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycogenolysis, insulin and glucagon secretion, and pituitary ACTH release. Moreover, AVP stimulates the expression of 11ß-hydroxysteroid-dehydrogenase-type 2 (11ß-HSD2) in mineralocorticosteroid cells. We explored whether apparent 11ß-HSD2 activity, estimated using urinary cortisol-to-cortisone ratio, modulates the association between plasma copeptin, as AVP surrogate, and insulin resistance/MetS in the general adult population. METHODS: This was a multicentric, family-based, cross-sectional sample of 1089 subjects, aged 18-90 years, 47% men, 13.4% MetS, in Switzerland. Mixed multivariable linear and logistic regression models were built to investigate the association of insulin resistance (HOMA-IR)/fasting glucose and MetS/Type 2 Diabetes with copeptin, while considering potential confounders or effect modifiers into account. Stratified results by age and 11ß-HSD2 activity were presented as appropriate. RESULTS: Plasma copeptin was higher in men [median 5.2, IQR (3.7-7.8) pmol/L] than in women [median 3.0, IQR (2.2-4.3) pmol/L], P < 0.0001. HOMA-IR was positively associated with copeptin after full adjustment if 11ß-HSD2 activity was high [ß (95% CI) = 0.32 (0.17-0.46), P < 0.001] or if age was high [ß (95% CI) = 0.34 (0.20-0.48), P < 0.001], but not if either 11ß-HSD2 activity or age was low. There was a positive association of type 2 diabetes with copeptin [OR (95% CI) = 2.07 (1.10-3.89), P = 0.024), but not for MetS (OR (95% CI) = 1.12 (0.74-1.69), P = 0.605), after full adjustment. CONCLUSIONS: Our data suggest that age and apparent 11ß-HSD2 activity modulate the association of copeptin with insulin resistance at the population level but not MeTS or diabetes. Further research is needed to corroborate these results and to understand the mechanisms underlying these findings.

Seasonality of sodium and potassium consumption in Switzerland. Data from three cross-sectional, population-based studies.

BACKGROUND AND AIM: Blood pressure displays a seasonal pattern. Whether this pattern is related to high sodium and/or low potassium intakes has not been investigated. We assessed if sodium and potassium consumption present a seasonal pattern. We also simulated the impact of seasonality of sodium consumption on systolic blood pressure levels. METHODS AND RESULTS: Data from three Swiss population-based studies (n = 2845). Sodium and potassium consumption were assessed by urinary excretion using 24 h urine collection. Seasonality was assessed using the cosinor model and was adjusted for study, gender, age, body mass index, antihypertensive drug treatment, urinary creatinine and atmospheric relative humidity. The effect of sodium variation on blood pressure levels was estimated using data from a recent meta-analysis. Both sodium and potassium excretions showed a seasonal pattern. For sodium, the nadir occurred between August and October, and the peak between February and April, with a multivariate-adjusted seasonal variation (difference between peak and nadir) of 9.2 mmol. For potassium, the nadir occurred in October and the peak in April, with a multivariate-adjusted seasonal variation of 4.0 mmol. Excluding participants on antihypertensive drug treatment or stratifying the analysis by gender cancelled the seasonality of sodium consumption. The maximum impact of the seasonal variation in sodium consumption on systolic blood pressure ranged from 0.4 to 1.1 mm Hg, depending on the model considered. CONCLUSION: Sodium and potassium consumptions present specific seasonal variations. These variations do not explain the seasonal variations in blood pressure levels.

New Short-Lived Isotope

Two short-lived isotopes ^{221}U and ^{222}U were produced as evaporation residues in the fusion reaction ^{50}Ti+^{176}Yb at the gas-filled recoil separator TASCA. An α decay with an energy of E_{α}=9.31(5) MeV and half-life T_{1/2}=4.7(7) µs was attributed to ^{222}U. The new isotope ^{221}U was identified in α-decay chains starting with E_{α}=9.71(5) MeV and T_{1/2}=0.66(14) µs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.

Methylated derivatives of myricetin enhance life span in Caenorhabditis elegans dependent on the transcription factor DAF-16.

Only certain flavonoids have been shown to enhance life span. This was pointed out for e.g. myricetin in the nematode Caenorhabditis elegans. However, the structural requirements responsible for this effect are not known. We used methylated derivatives of myricetin (laricitrin, syringetin, myricetintrimethylether) to investigate if free OH moieties in the B-ring are necessary for the life span extending effect. In analogy to myricetin, all derivatives increased the life span, decreased oxidative stress (DCF) and decreased the accumulation of lipofuscin. In contrast to myricetin, the methylated compounds strongly enhanced the resistance against thermal stress. Furthermore, treatment with the derivatives induced a much stronger nuclear localization of the DAF-16 transcription factor (FoxO homologue). Additionally, no antioxidant effects and only minor effects on life span prolongation and stress resistance were detectable for the methylated compounds in a DAF-16 deficient nematode strain. Comparable to the dietary flavonoid myricetin, the methylated myricetin derivatives laricitrin, syringetin and myricetintrimethylether strongly enhance the life span of C. elegans. Therefore, OH groups of ring B are not necessary for this effect. Only the methylated compounds increase the stress resistance of the nematode which was dependent on DAF-16. These findings suggest that methylation of myricetin increases the biofunctionality.

48Ca+249Bk fusion reaction leading to element Z = 117: long-lived α-decaying 270Db and discovery of 266Lr.

The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-µs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."

Spectroscopy of element 115 decay chains.

A high-resolution α, x-ray, and γ-ray coincidence spectroscopy experiment was conducted at the GSI Helmholtzzentrum für Schwerionenforschung. Thirty correlated α-decay chains were detected following the fusion-evaporation reaction 48Ca + 243Am. The observations are consistent with previous assignments of similar decay chains to originate from element Z=115. For the first time, precise spectroscopy allows the derivation of excitation schemes of isotopes along the decay chains starting with elements Z>112. Comprehensive Monte Carlo simulations accompany the data analysis. Nuclear structure models provide a first level interpretation.

Signatures of the Z = 82 shell closure in α-decay process.

In recent experiments at the velocity filter Separator for Heavy Ion reaction Products (SHIP) (GSI, Darmstadt), an extended and improved set of α-decay data for more than 20 of the most neutron-deficient isotopes in the region from lead to thorium was obtained. The combined analysis of this newly available α-decay data, of which the (186)Po decay is reported here, allowed us for the first time to clearly show that crossing the Z = 82 shell to higher proton numbers strongly accelerates the α decay. From the experimental data, the α-particle formation probabilities are deduced following the Universal Decay Law approach. The formation probabilities are discussed in the framework of the pairing force acting among the protons and the neutrons forming the α particle. A striking resemblance between the phenomenological pairing gap deduced from experimental binding energies and the formation probabilities is noted. These findings support the conjecture that both the N = 126 and Z = 82 shell closures strongly influence the α-formation probability.

Energy efficient neural stimulation: coupling circuit design and membrane biophysics.

The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson's disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.

Direct mapping of nuclear shell effects in the heaviest elements.

Quantum-mechanical shell effects are expected to strongly enhance nuclear binding on an "island of stability" of superheavy elements. The predicted center at proton number Z = 114, 120, or 126 and neutron number N = 184 has been substantiated by the recent synthesis of new elements up to Z = 118. However, the location of the center and the extension of the island of stability remain vague. High-precision mass spectrometry allows the direct measurement of nuclear binding energies and thus the determination of the strength of shell effects. Here, we present such measurements for nobelium and lawrencium isotopes, which also pin down the deformed shell gap at N = 152.

Uninephrectomy reduces 11ß-hydroxysteroid dehydrogenase type 1 and type 2 concomitantly with an increase in blood pressure in rats.

Renal allograft donors are at risk of developing hypertension. Here, we hypothesized that this risk is at least in part explained by an enhanced intracellular availability of 11ß-hydroxyglucocorticoids due to an increased 11ß-hydroxysteroid dehydrogenase type 1 enzyme (11ß-HSD1), an intracellular prereceptor activator of biologically inactive 11-ketocorticosteroids in the liver, and/or a diminished 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), an inactivator of 11ß-hydroxyglucocorticoids in the kidney. To test this hypothesis, uninephrectomized (UNX) (n=9) and sham-operated (n=10) adult Sprague-Dawley rats were investigated. Mean arterial blood pressure and heart rate were measured continuously by telemetry for 6 days in week 5 after UNX. The mRNA of 11ß-Hsd1 and 11ß-Hsd2 in liver and kidney tissues were assessed by RT-PCR and the 11ß-HSD activities were directly quantified in their corresponding tissues by determining the ratios of (tetrahydrocorticosterone+5α-tetrahydrocorticosterone)/tetrahydrodehydrocorticosterone ((THB+5α-THB)/THA) and of corticosterone/dehydrocorticosterone (B/A) by gas chromatography-mass spectrometry. The apparent total body activities of 11ß-HSD1 and 11ß-HSD2 were estimated using the urinary and plasma ratios of (THB+5α-THB)/THA and B/A. Mean arterial blood pressure was increased after UNX when compared with sham operation. Hepatic mRNA content of 11ß-Hsd1 and hepatic, plasma, and urinary ratios of (THB+5α-THB)/THA were decreased after UNX, indicating diminished access of glucocorticoids to its receptors. In renal tissue, 11ß-Hsd2 mRNA was reduced and B/A ratios measured in kidney, plasma, and urine were increased, indicating reduced 11ß-HSD2 activity and enhanced access of glucocorticoids to mineralocorticoid receptors. Both 11ß-HSD1 and 11ß-HSD2 are downregulated after UNX in rats, a constellation considered to induce hypertension.

Dynamics and sensitivity analysis of high-frequency conduction block.

The local delivery of extracellular high-frequency stimulation (HFS) has been shown to be a fast acting and quickly reversible method of blocking neural conduction and is currently being pursued for several clinical indications. However, the mechanism for this type of nerve block remains unclear. In this study, we investigate two hypotheses: (1) depolarizing currents promote conduction block via inactivation of sodium channels and (2) the gating dynamics of the fast sodium channel are the primary determinate of minimal blocking frequency. Hypothesis 1 was investigated using a combined modeling and experimental study to investigate the effect of depolarizing and hyperpolarizing currents on high-frequency block. The results of the modeling study show that both depolarizing and hyperpolarizing currents play an important role in conduction block and that the conductance to each of three ionic currents increases relative to resting values during HFS. However, depolarizing currents were found to promote the blocking effect, and hyperpolarizing currents were found to diminish the blocking effect. Inward sodium currents were larger than the sum of the outward currents, resulting in a net depolarization of the nodal membrane. Our experimental results support these findings and closely match results from the equivalent modeling scenario: intra-peritoneal administration of the persistent sodium channel blocker ranolazine resulted in an increase in the amplitude of HFS required to produce conduction block in rats, confirming that depolarizing currents promote the conduction block phenomenon. Hypothesis 2 was investigated using a spectral analysis of the channel gating variables in a single-fiber axon model. The results of this study suggested a relationship between the dynamical properties of specific ion channel gating elements and the contributions of corresponding conductances to block onset. Specifically, we show that the dynamics of the fast sodium inactivation gate are too slow to track the high-frequency changes in membrane potential during HFS, and that the behavior of the fast sodium current was dominated by the low-frequency depolarization of the membrane. As a result, in the blocked state, only 5.4% of nodal sodium channels were found to be in the activatable state in the node closest to the blocking electrode, resulting in conduction block. Moreover, we find that the corner frequency for the persistent sodium channel activation gate corresponds to the frequency below which high-frequency stimuli of arbitrary amplitude are incapable of inducing conduction block.

Electrical conduction block in large nerves: high-frequency current delivery in the nonhuman primate.

Recent studies have made significant progress toward the clinical implementation of high-frequency conduction block (HFB) of peripheral nerves. However, these studies were performed in small nerves, and questions remain regarding the nature of HFB in large-diameter nerves. This study in nonhuman primates shows reliable conduction block in large-diameter nerves (up to 4.1 mm) with relatively low-threshold current amplitude and only moderate nerve discharge prior to the onset of block.