JOKARUS - Design of a compact optical iodine frequency reference for a sounding rocket mission

We present the design of a compact absolute optical frequency reference for space applications based on hyperfine transitions in molecular iodine with a targeted fractional frequency instability of better than $3\cdot 10^{-14}$. It is based on a micro-integrated extended cavity diode laser with integrated optical amplifier, fiber pigtailed second harmonic generation wave-guide modules, and a quasi-monolithic spectroscopy setup with operating electronics. The instrument described here is scheduled for launch end of 2017 aboard the TEXUS 54 sounding rocket as an important qualification step towards space application of iodine frequency references and related technologies. The payload will operate autonomously and its optical frequency will be compared to an optical frequency comb during its space flight

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy

Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 ± 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) ≥40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% ± 9.3%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%–12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition

Interference in strong-field ionization of a two-centre atomic system

Strong-field photoionization of argon dimers by a few-cycle laser pulse is investigated using electron-ion coincidence momentum spectroscopy. The momentum distribution of the photoelectrons exhibits interference due to the emission from the two atomic argon centres, in analogy with a Young's doubleslit experiment. However, a simulation of the dimer photoelectron momentum spectrum based on the atomic spectrum supplemented with a theoretically derived interference term leads to distinct deviations from the experimental result. The deviations may have their origin in a complex electron dynamics during strong-field ionization of the Ar2 dimer. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft

Compact Low-Noise Photonic Microwave Generation From Commercial Low-Noise Lasers

We demonstrate how phase-locking a whispering gallery mode-stabilized semiconductor laser to a high-stability Erbium-based distributed feedback fiber laser makes an outstanding optical reference for photonic microwave generation using an optical frequency comb. Using only commercially available compact lasers, it allows generation of a 12 GHz microwave signal with absolute levels of phase noise below-47 dBc/Hz at 1 Hz and-170 dBc/Hz at 50 kHz from the carrier. Index Terms-Phase noise, microwave source, optical frequency comb, distributed feedback laser, whispering gallery mode resonator (WGMR)

COMPASSO - In-orbit Verification of Optical Key Technologies for Future GNSS - Mission Description

All GNSS programs (i.e. Galileo, GPS, BeiDou, GLONASS, etc.) undergo a permanent process of modernization and improvement of their ground and space segments. Driven by increasing user demands, all programs aim at pushing the boundary of today's position, navigation, and timing technologies to pave the way for more flexible, robust, and resilient GNSSs. A promising way to improve GNSS architectures is the use of optical technologies and more specifically: optical clocks and optical inter-satellite links (ISL). Optical clocks could back-up or replace the currently used microwave clocks, having the potential to improve GNSS position determination enabled by their lower frequency instabilities. In combination with optical inter-satellite links, optical clock technologies enable new GNSS architectures, e.g., by synchronization of distant optical frequency references within the satellite constellation using time and frequency transfer techniques. The aim of the COMPASSO mission - which is an ongoing project and has recently finalized the preliminary system design phase (Phase B) - is to demonstrate new optical technologies relating to satellite navigation. Within the mission, various optical technologies will be further developed and tested with regard to space suitability and operational conditions. This paper details the objectives, status, mission scenario, payload setup and the main optical technologies constituting COMPASSO: iodine frequency references, optical frequency comb, and laser terminal for communication and ranging

Ultra-low phase noise frequency-comb-based microwave generation and characterization

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JOKARUS—An optical absolute frequency reference on a sounding rocket based on molecular iodine

We present the JOKARUS payload, which was launched aboard the TEXUS 54 sounding rocket mission in May ’18. It demonstrated the first iodine-based optical frequency reference in space, using a frequency-doubled 1064 nm diode laser for Doppler-free saturated-absorption spectroscopy of the R56(32-0) transition in molecular iodine. In ground-based operation, this optical oscillator provides a fractional frequency stability of 4 ⋅ 10-13 at an integration time of 1 s. During the 15-minute flight, the laser frequency was measured by an optical frequency comb, confirming autonomous operation as an absolute frequency reference in spac

Ultra-low phase noise frequency-comb-based microwave generation and characterization

International audienc