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Abstract The determination of the effective electron neutrino mass via kinematic analysis of beta and electron capture spectra is considered to be model-independent since it relies on energy and momentum conservation. At the same time the precise description of the expected spectrum goes beyond the simple phase space term. In particular for electron capture processes, many-body electron-electron interactions lead to additional structures besides the main resonances in calorimetrically measured spectra. A precise description of the $$^{163}$$ 163 Ho spectrum is fundamental for understanding the impact of low intensity structures at the endpoint region where a finite neutrino mass affects the shape most strongly. We present a low-background and high-energy resolution measurement of the $$^{163}$$ 163 Ho spectrum obtained in the framework of the ECHo experiment. We study the line shape of the main resonances and multiplets with intensities spanning three orders of magnitude. We discuss the need to introduce an asymmetric line shape contribution due to Auger–Meitner decay of states above the auto-ionisation threshold. With this we determine an enhancement of count rate at the endpoint region of about a factor of 2, which in turn leads to an equal reduction in the required exposure of the experiment to achieve a given sensitivity on the effective electron neutrino mass.

Familial hypercholesterolemia (FH) is one of the most common genetically inherited disorders in the world. Children with severe heterozygous FH (HeFH), i.e. untreated low-density lipoprotein cholesterol (LDL-C) levels above the 90th percentile for age and sex among FH mutation carriers, can have LDL-C levels that overlap levels of children with homozygous FH (HoFH), but treatment regimen and cardiovascular follow-up to prevent cardiovascular disease are less intensive in children with severe HeFH. In children with HoFH, subclinical atherosclerosis can already be present using computed tomography coronary angiography (CTCA). The question remains whether this is also the case in children with severe HeFH who have a high exposure to elevated LDL-C levels from birth onwards as well. We calculated the cumulative LDL-C exposure (CEtotal [mmol]) in four children with severe HeFH and performed computed tomography coronary angiography (CTCA). These children, aged 13, 14, 15 and 18 years, had CEtotal of 71.3, 97.8, 103.6 and 136.1 mmol, respectively. None of them showed abnormalities on cardiovascular imaging, despite high LDL-C exposure. The results of this study, do not give us an indication to recommend performing CTCA routinely in children with severe HeFH.

Therapeutic Area: ASCVD /CVD Risk Reduction Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels. Currently, few treatments effectively lower LDL-C levels in pediatric patients with HoFH. Here, we report the efficacy and safety of evinacumab, a monoclonal antibody inhibitor of angiopoietin-like 3, in pediatric patients with HoFH. Methods: This is a three-part, open-label study (NCT04233918); Part B results are reported here. Part B enrolled 14 patients with HoFH 5–11 years old with LDL-C >130 mg/dL on optimized lipid-lowering therapy, including apheresis and lomitapide. All patients received intravenous evinacumab 15 mg/kg every 4 weeks. Results: All 14 patients completed Part B. Evinacumab treatment reduced mean (standard deviation) LDL-C from 263.7 (91.0) mg/dL at baseline to 131.8 (109.8) mg/dL at Week 24, with a mean (standard error [SE]) percent reduction of −48.3% (10.4%). Mean (SE) reductions in apolipoprotein B (−41.3% [9.0%]), non-high-density lipoprotein cholesterol (−48.9% [9.8%]), and total cholesterol (−49.1% [8.1%]) were also observed. Furthermore, percent LDL-C reduction observed at Week 24 from baseline based on the baseline LDL-C values or the presence of lomitapide treatment are presented in a Table. Additionally, the percent change from baseline in Lp(a) at Week 24 according to baseline apheresis status (Yes vs No) was similar: −43.7% (1.6%) versus −32.7% (1.4%), respectively. Treatment-emergent adverse events (TEAEs) occurred in 10 (71.4%) patients; no deaths or treatment discontinuations due to TEAEs were reported. Conclusions: Evinacumab substantially reduced LDL-C levels and other key atherogenic lipid parameters in pediatric patients with HoFH additive to any pre-existing treatment (including apheresis and lomitapide). Evinacumab was generally well-tolerated.

Background: Adipose-derived Stem Cells (ASCs) present great potential for reconstructive procedures. Currently, isolation by enzyme digestion and culturing using xenogenic substances remain the gold standard, impairing clinical use. Methods: Abdominal lipo-aspirate and blood samples were obtained from healthy patients. A novel mechanical isolation method for ASCs was compared to (the standard) collagenase digestion. ASCs are examined by flowcytometry and multilineage differentiation assays. Cell cultures were performed without xenogenic or toxic substances, using autologous plasma extracted from peripheral blood. After eGFP-transfection, an in vivo differentiation assay was performed. Results: Mechanical isolation is more successful in isolating CD34+/CD31−/CD45−/CD13+/CD73+/CD146− ASCs from lipo-aspirate than isolation via collagenase digestion (p

The evolution of heathlands during the Holocene has been registered in various soil records. Paleoecological analyses of these records enable reconstruction of the changing economic and cultural management of heaths and the consequences for landscape and soils. Heaths are characteristic components of cultural landscape mosaics on sandy soils in the Netherlands. The natural habitat of heather species was moorland. At first, natural events like forest fires and storms caused small-scale forest degradation; in addition on that, the forest degradation accelerated due to cultural activities like forest grazing, wood cutting, and shifting cultivation. Heather plants invaded degraded forest soils, and heaths developed. People learned to use the heaths for economic and cultural purposes. The impact of the heath management on landscape and soils was registered in soil records of barrows, drift sand sequences, and plaggic Anthrosols. Based on pollen diagrams of such records we could reconstruct that heaths were developed and used for cattle grazing before the Bronze Age. During the late Neolithic, the Bronze Age, and Iron Age, people created the barrow landscape on the ancestral heaths. After the Iron Age, people probably continued with cattle grazing on the heaths and plaggic agriculture until the early Middle Ages. Severe forest degradation by the production of charcoal for melting iron during the Iron Age till the 6th–7th century and during the 11th–13th century for the trade of wood resulted in extensive sand drifting, a threat to the valuable heaths. The introduction of the deep, stable economy and heath sods digging in the course of the 18th century resulted in acceleration of the rise of plaggic horizons, severe heath degradation, and again extension of sand drifting. At the end of the 19th century heath lost its economic value due to the introduction of chemical fertilizers. The heaths were transformed into "new" arable fields and forests, and due to deep ploughing most soil archives were destroyed. Since AD 1980, the remaining relicts of the ancestral heaths are preserved and restored in the frame of the programs to improve the regional and national geo-biodiversity. Despite the realization of many heath restoration projects during the last decades, the area of the present heaths is just a fraction of the heath areal in AD 1900.

Signal-dependent RNA polymerase II (RNA Pol II) productive elongation is an integral component of gene transcription, including that of immediate early genes (IEGs) induced by neuronal activity. However, it remains unclear how productively elongating RNA Pol II overcomes nucleosomal barriers. Using RNAi, three degraders, and several small-molecule inhibitors, we show that the mammalian switch/sucrose non-fermentable (SWI/SNF) complex of neurons (neuronal BRG1/BRM-associated factor or nBAF) is required for activity-induced transcription of neuronal IEGs, including Arc. The nBAF complex facilitates promoter-proximal RNA Pol II pausing and signal-dependent RNA Pol II recruitment (loading) and, importantly, mediates productive elongation in the gene body via interaction with the elongation complex and elongation-competent RNA Pol II. Mechanistically, RNA Pol II elongation is mediated by activity-induced nBAF assembly (especially ARID1A recruitment) and its ATPase activity. Together, our data demonstrate that the nBAF complex regulates several aspects of RNA Pol II transcription and reveal mechanisms underlying activity-induced RNA Pol II elongation. These findings may offer insights into human maladies etiologically associated with mutational interdiction of BAF functions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

We present the measurements of individual bound electron g factors of ^{20}Ne^{9+} and ^{22}Ne^{9+} on the relative level of 0.1 parts per billion. The comparison with theory represents the most stringent test of bound-state QED in strong electric fields. A dedicated mass measurement results in m(^{20}Ne)=19.992 440 168 77(9)  u, which improves the current literature value by a factor of 18, disagrees by 4 standard deviations, and represents the most precisely measured mass value in atomic mass units. Together, these measurements yield an electron mass on the relative level of 0.1 ppb with m_{e}=5.485 799 090 99(59)×10^{-4}  u as well as a factor of seven improved m(^{22}Ne)=21.991 385 098 2(26)  u.

Highly charged ions (HCIs) offer many opportunities for next-generation clock research due to the vast landscape of available electronic transitions in different charge states. The development of extreme ultraviolet frequency combs has enabled the search for clock transitions based on shorter wavelengths in HCIs. However, without initial knowledge of the energy of the clock states, these narrow transitions are difficult to be probed by lasers. In this Letter, we provide experimental observation and theoretical calculation of a long-lived electronic state in Nb-like Pb^{41+} that could be used as a clock state. With the mass spectrometer PENTATRAP, the excitation energy of this metastable state is directly determined as a mass difference at an energy of 31.2(8) eV, corresponding to one of the most precise relative mass determinations to date with a fractional uncertainty of 4×10^{-12}. This experimental result agrees within 1σ with two partially different ab initio multiconfiguration Dirac-Hartree-Fock calculations of 31.68(13) eV and 31.76(35) eV, respectively. With a calculated lifetime of 26.5(5.3) days, the transition from this metastable state to the ground state bears a quality factor of 1.1×10^{23} and allows for the construction of a HCI clock with a fractional frequency instability of <10^{-19}/sqrt[τ].

In this paper, we report on the development of a fast high-voltage switch, which is based on two enhancement mode N-channel silicon carbide metal-oxide-semiconductor field-effect transistors in push-pull configuration. The switch is capable of switching high voltages up to 600 V on capacitive loads with rise and fall times on the order of 10 ns and pulse widths ≥20 ns. Using this switch, it was demonstrated that, from the charge state distribution of bunches of highly charged ions ejected from an electron beam ion trap with a specific kinetic energy, single charge states can be separated by fast switching of the high voltage applied to a Bradbury-Nielsen Gate with a resolving power of about 100.

The absolute atomic mass of 208 Pb has been determined with a fractional uncertainty of 7 × 10 - 11 by measuring the cyclotron-frequency ratio R of 208 Pb 41 + to 132 Xe 26 + with the high-precision Penning-trap mass spectrometer Pentatrap and computing the binding energies E Pb and E Xe of the missing 41 and 26 atomic electrons, respectively, with the ab initio fully relativistic multi-configuration Dirac-Hartree-Fock (MCDHF) method. R has been measured with a relative precision of 9 × 10 - 12 . E Pb and E Xe have been computed with an uncertainty of 9.1 eV and 2.1 eV, respectively, yielding 207.976 650 571 ( 14 )  u ( u = 9.314 941 024 2 ( 28 ) × 10 8  eV/c 2 ) for the 208 Pb neutral atomic mass. This result agrees within 1.2 σ with that from the Atomic-Mass Evaluation (AME) 2020, while improving the precision by almost two orders of magnitude. The new mass value directly improves the mass precision of 14 nuclides in the region of Z = 81-84 and is the most precise mass value with A > 200 . Thus, the measurement establishes a new region of reference mass values which can be used e.g. for precision mass determination of transuranium nuclides, including the superheavies., (© The Author(s) 2022.)

The possibility of applying active feedback to a single ion in a Penning trap using a fully digital system is demonstrated. Previously realized feedback systems rely on analog circuits that are susceptible to environmental fluctuations and long term drifts, as well as being limited to the specific task they were designed for. The presented system is implemented using a field-programmable gate array (FPGA)-based platform (STEMlab), offering greater flexibility, higher temporal stability, and the possibility for highly dynamic variation of feedback parameters. The system's capabilities were demonstrated by applying feedback to the ion detection system primarily consisting of a resonant circuit. This allowed shifts in its resonance frequency of up to several kHz and free modification of its quality factor within two orders of magnitude, which reduces the temperature of a single ion by a factor of 6. Furthermore, a phase-sensitive detection technique for the axial ion oscillation was implemented, which reduces the current measurement time by two orders of magnitude, while simultaneously eliminating model-related systematic uncertainties. The use of FPGA technology allowed the implementation of a fully-featured data acquisition system, making it possible to realize feedback techniques that require constant monitoring of the ion signal. This was successfully used to implement a single-ion self-excited oscillator.

The cyclotron frequency ratio of ^{187}Os^{29+} to ^{187}Re^{29+} ions was measured with the Penning-trap mass spectrometer PENTATRAP. The achieved result of R=1.000 000 013 882(5) is to date the most precise such measurement performed on ions. Furthermore, the total binding-energy difference of the 29 missing electrons in Re and Os was calculated by relativistic multiconfiguration methods, yielding the value of ΔE=53.5(10)  eV. Finally, using the achieved results, the mass difference between neutral ^{187}Re and ^{187}Os, i.e., the Q value of the β^{-} decay of ^{187}Re, is determined to be 2470.9(13) eV.

State-of-the-art optical clocks 1 achieve precisions of 10 -18 or better using ensembles of atoms in optical lattices 2,3 or individual ions in radio-frequency traps 4,5 . Promising candidates for use in atomic clocks are highly charged ions 6 (HCIs) and nuclear transitions 7 , which are largely insensitive to external perturbations and reach wavelengths beyond the optical range 8 that are accessible to frequency combs 9 . However, insufficiently accurate atomic structure calculations hinder the identification of suitable transitions in HCIs. Here we report the observation of a long-lived metastable electronic state in an HCI by measuring the mass difference between the ground and excited states in rhenium, providing a non-destructive, direct determination of an electronic excitation energy. The result is in agreement with advanced calculations. We use the high-precision Penning trap mass spectrometer PENTATRAP to measure the cyclotron frequency ratio of the ground state to the metastable state of the ion with a precision of 10 -11 -an improvement by a factor of ten compared with previous measurements 10,11 . With a lifetime of about 130 days, the potential soft-X-ray frequency reference at 4.96 × 10 16 hertz (corresponding to a transition energy of 202 electronvolts) has a linewidth of only 5 × 10 -8 hertz and one of the highest electronic quality factors (10 24 ) measured experimentally so far. The low uncertainty of our method will enable searches for further soft-X-ray clock transitions 8,12 in HCIs, which are required for precision studies of fundamental physics 6 .

First ever measurements of the ratios of free cyclotron frequencies of heavy, highly charged ions with Z>50 with relative uncertainties close to 10^{-11} are presented. Such accurate measurements have become realistic due to the construction of the novel cryogenic multi-Penning-trap mass spectrometer PENTATRAP. Based on the measured frequency ratios, the mass differences of five pairs of stable xenon isotopes, ranging from ^{126}Xe to ^{134}Xe, have been determined. Moreover, the first direct measurement of an electron binding energy in a heavy highly charged ion, namely of the 37th atomic electron in xenon, with an uncertainty of a few eV is demonstrated. The obtained value agrees with the calculated one using two independent, different implementations of the multiconfiguration Dirac-Hartree-Fock method. PENTATRAP opens the door to future measurements of electron binding energies in highly charged heavy ions for more stringent tests of bound-state quantum electrodynamics in strong electromagnetic fields and for an investigation of the manifestation of light dark matter in isotopic chains of certain chemical elements.

This paper reports on the development and testing of a novel, highly efficient technique for the injection of very rare species into electron beam ion traps (EBITs) for the production of highly charged ions (HCI). It relies on in-trap laser-induced desorption of atoms from a sample brought very close to the electron beam resulting in a very high capture efficiency in the EBIT. We have demonstrated a steady production of HCI of the stable isotope 165 Ho from samples of only 10 12 atoms (∼300 pg) in charge states up to 45+. HCI of these species can be subsequently extracted for use in other experiments or stored in the trapping volume of the EBIT for spectroscopic measurements. The high efficiency of this technique extends the range of rare isotope HCIs available for high-precision atomic mass and spectroscopic measurements. A first application of this technique is the production of HCI of the synthetic radioisotope 163 Ho for a high-precision measurement of the Q EC -value of the electron capture in 163 Ho within the "Electron Capture in Holmium" experiment [L. Gastaldo et al., J. Low Temp. Phys. 176, 876-884 (2014); L. Gastaldo et al., Eur. Phys. J.: Spec. Top. 226, 1623-1694 (2017)] (ECHo collaboration) ultimately leading to a measurement of the electron neutrino mass with an uncertainty on the sub electronvolt level.