Measuring the α-particle charge radius with muonic helium-4 ions.

The energy levels of hydrogen-like atomic systems can be calculated with great precision. Starting from their quantum mechanical solution, they have been refined over the years to include the electron spin, the relativistic and quantum field effects, and tiny energy shifts related to the complex structure of the nucleus. These energy shifts caused by the nuclear structure are vastly magnified in hydrogen-like systems formed by a negative muon and a nucleus, so spectroscopy of these muonic ions can be used to investigate the nuclear structure with high precision. Here we present the measurement of two 2S-2P transitions in the muonic helium-4 ion that yields a precise determination of the root-mean-square charge radius of the α particle of 1.67824(83) femtometres. This determination from atomic spectroscopy is in excellent agreement with the value from electron scattering1, but a factor of 4.8 more precise, providing a benchmark for few-nucleon theories, lattice quantum chromodynamics and electron scattering. This agreement also constrains several beyond-standard-model theories proposed to explain the proton-radius puzzle2-5, in line with recent determinations of the proton charge radius6-9, and establishes spectroscopy of light muonic atoms and ions as a precise tool for studies of nuclear properties.

Multipass laser cavity for efficient transverse illumination of an elongated volume.

A multipass laser cavity is presented which can be used to illuminate an elongated volume from a transverse direction. The illuminated volume can also have a very large transverse cross section. Convenient access to the illuminated volume is granted. The multipass cavity is very robust against misalignment, and no active stabilization is needed. The scheme is suitable for example in beam experiments, where the beam path must not be blocked by a laser mirror, or if the illuminated volume must be very large. This cavity was used for the muonic-hydrogen experiment in which 6 µm laser light illuminated a volume of 7 × 25 × 176 mm3, using mirrors that are only 12 mm in height. We present our measurement of the intensity distribution inside the multipass cavity and show that this is in good agreement with our simulation.

Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease.

In neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and prion diseases, deposits of aggregated disease-specific proteins are found. Oligomeric aggregates are presumed to be the key neurotoxic agent. Here we describe the novel oligomer modulator anle138b [3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole], an aggregation inhibitor we developed based on a systematic high-throughput screening campaign combined with medicinal chemistry optimization. In vitro, anle138b blocked the formation of pathological aggregates of prion protein (PrP(Sc)) and of α-synuclein (α-syn), which is deposited in PD and other synucleinopathies such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Notably, anle138b strongly inhibited all prion strains tested including BSE-derived and human prions. Anle138b showed structure-dependent binding to pathological aggregates and strongly inhibited formation of pathological oligomers in vitro and in vivo both for prion protein and α-synuclein. Both in mouse models of prion disease and in three different PD mouse models, anle138b strongly inhibited oligomer accumulation, neuronal degeneration, and disease progression in vivo. Anle138b had no detectable toxicity at therapeutic doses and an excellent oral bioavailability and blood-brain-barrier penetration. Our findings indicate that oligomer modulators provide a new approach for disease-modifying therapy in these diseases, for which only symptomatic treatment is available so far. Moreover, our findings suggest that pathological oligomers in neurodegenerative diseases share structural features, although the main protein component is disease-specific, indicating that compounds such as anle138b that modulate oligomer formation by targeting structure-dependent epitopes can have a broad spectrum of activity in the treatment of different protein aggregation diseases.

Improved x-ray detection and particle identification with avalanche photodiodes.

Avalanche photodiodes are commonly used as detectors for low energy x-rays. In this work, we report on a fitting technique used to account for different detector responses resulting from photoabsorption in the various avalanche photodiode layers. The use of this technique results in an improvement of the energy resolution at 8.2 keV by up to a factor of 2 and corrects the timing information by up to 25 ns to account for space dependent electron drift time. In addition, this waveform analysis is used for particle identification, e.g., to distinguish between x-rays and MeV electrons in our experiment.