The optical calcium frequency standards of PTB and NIST

We describe the current status of the Ca optical frequency standards with laser-cooled neutral atoms realized in two different laboratories for the purpose of developing a possible future optical atomic clock. Frequency measurements performed at the Physikalisch-Technische Bundesanstalt (PTB) and the National Institute of Standards and Technology (NIST) make the frequency of the clock transition of 40Ca one of the best known optical frequencies (relative uncertainty 1.2e-14) and the measurements of this frequency in both laboratories agree to well within their respective uncertainties. Prospects for improvement by orders of magnitude in the relative uncertainty of the standard look feasible.Comment: 13 pages, 11 figures, to appear in Comptes Rendus Physiqu

A clock network for geodesy and fundamental science

Leveraging the unrivaled performance of optical clocks in applications in fundamental physics beyond the standard model, in geo-sciences, and in astronomy requires comparing the frequency of distant optical clocks truthfully. Meeting this requirement, we report on the first comparison and agreement of fully independent optical clocks separated by 700 km being only limited by the uncertainties of the clocks themselves. This is achieved by a phase-coherent optical frequency transfer via a 1415 km long telecom fiber link that enables substantially better precision than classical means of frequency transfer. The fractional precision in comparing the optical clocks of three parts in $10^{17}$ was reached after only 1000 s averaging time, which is already 10 times better and more than four orders of magnitude faster than with any other existing frequency transfer method. The capability of performing high resolution international clock comparisons paves the way for a redefinition of the unit of time and an all-optical dissemination of the SI-second.Comment: 14 pages, 3 figures, 1 tabl

Low-dose metronomic chemotherapy as an efficient treatment option in metastatic breast cancer : results of an exploratory case–control study

PURPOSE There is growing interest in low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case–control analysis, we compared the efficacy of LDMC and conventional chemotherapy (CCT) in MBC. METHODS Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two controls who received CCT. Age, number of chemotherapy lines and metastatic sites as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate longer than 24 weeks (DCR). Secondary endpoints were progression-free survival (PFS), duration of response (DoR) and subgroup analyses using the matching criteria. RESULTS 40 cases and 80 controls entered the study. 30.0% patients with LDMC and 22.5% patients with CCT showed DCR (p = 0.380). The median PFS was 12.0 weeks in both groups (p = 0.218) and the median DoR was 31.0 vs. 20.5 weeks (p = 0.383), respectively. Among younger patients, DCR was 40.0% in LDMC vs. 25.0% in the CCT group (p = 0.249). DCR was achieved in 33.3% vs. 26.2% non-heavily pretreated patients (p = 0.568) and in 36.0% vs. 18.0% patients without multiple metastases (p = 0.096), respectively. In the HR-positive group, 30.0% LDMC vs. 28.3% CCT patients showed DCR (p = 1.000). Among triple-negative patients, DCR was achieved in 30.0% LDMC and 5.0% CCT patients (p = 0.095). CONCLUSIONS We demonstrated a similar efficacy of LDMC compared to CCT in the treatment of MBC. Thus, LDMC may be a valuable treatment option in selected MBC patients

Absolute Frequency Measurements of the Hg^+ and Ca Optical Clock Transitions with a Femtosecond Laser

The frequency comb created by a femtosecond mode-locked laser and a microstructured fiber is used to phase coherently measure the frequencies of both the Hg^+ and Ca optical standards with respect to the SI second as realized at NIST. We find the transition frequencies to be f_Hg=1 064 721 609 899 143(10) Hz and f_Ca=455 986 240 494 158(26) Hz, respectively. In addition to the unprecedented precision demonstrated here, this work is the precursor to all-optical atomic clocks based on the Hg^+ and Ca standards. Furthermore, when combined with previous measurements, we find no time variations of these atomic frequencies within the uncertainties of |(df_Ca/dt)/f_Ca| < 8 x 10^{-14} yr^{-1}, and |(df_Hg/dt)/f_Hg|< 30 x 10^{-14} yr^{-1}.Comment: 6 pages, including 4 figures. RevTex 4. Submitted to Phys. Rev. Let

Ultra-precise measurement of optical frequency ratios

We developed a novel technique for frequency measurement and synthesis, based on the operation of a femtosecond comb generator as transfer oscillator. The technique can be used to measure frequency ratios of any optical signals throughout the visible and near-infrared part of the spectrum. Relative uncertainties of $10^{-18}$ for averaging times of 100 s are possible. Using a Nd:YAG laser in combination with a nonlinear crystal we measured the frequency ratio of the second harmonic $\nu_{SH}$ at 532 nm to the fundamental $\nu_0$ at 1064 nm, $\nu_{SH}/\nu_0 = 2.000 000 000 000 000 001 \times (1 \pm 7 \times 10^{-19})$.Comment: 4 pages, 4 figure

Remote frequency measurement of the 1S0-3P1 transition in laser cooled Mg-24

We perform Ramsey-Bord\'e spectroscopy on laser-cooled magnesium atoms in free fall to measure the 1S0 \rightarrow 3P1 intercombination transition frequency. The measured value of 655 659 923 839 730 (48) Hz is consistent with our former atomic beam measurement (Friebe et al 2008 Phys. Rev. A 78 033830). We improve upon the fractional accuracy of the previous measurement by more than an order of magnitude to 7e-14. The magnesium frequency standard was referenced to a fountain clock of the Physikalisch-Technische Bundesanstalt (PTB) via a phase-stabilized telecom fiber link and its stability was characterized for interrogation times up to 8000 s. The high temperature of the atomic ensemble leads to a systematic shift due to the motion of atoms across the spectroscopy beams. In our regime, this leads to a counterintuitive reduction of residual Doppler shift with increasing resolution. Our theoretical model of the atom-light interaction is in agreement with the observed effect and allows us to quantify its contribution in the uncertainty budget.Comment: 16 pages, 8 figures. Accepted in New Journal of Physic

Roadmap towards the redefinition of the second

This paper outlines the roadmap towards the redefinition of the second, which was recently updated by the CCTF Task Force created by the CCTF in 2020. The main achievements of optical frequency standards (OFS) call for reflection on the redefinition of the second, but open new challenges related to the performance of the OFS, their contribution to time scales and UTC, the possibility of their comparison, and the knowledge of the Earth's gravitational potential to ensure a robust and accurate capacity to realize a new definition at the level of 10-18 uncertainty. The mandatory criteria to be achieved before redefinition have been defined and their current fulfilment level is estimated showing the fields that still needed improvement. The possibility to base the redefinition on a single or on a set of transitions has also been evaluated. The roadmap indicates the steps to be followed in the next years to be ready for a sound and successful redefinition

Phase- coherent comparison of two optical frequency standards over 146 km using a telecommunication fiber link

We have explored the performance of two "dark fibers" of a commercial telecommunication fiber link for a remote comparison of optical clocks. The two fibers, linking the Leibniz University of Hanover (LUH) with the Physi-kalisch-Technische Bundesanstalt (PTB) in Braunschweig, are connected in Hanover to form a total fiber length of 146 km. At PTB the performance of an optical frequency standard operating at 456 THz was imprinted to a cw trans-fer laser at 194 THz, and its frequency was transmitted over the fiber. In order to detect and compensate phase noise related to the optical fiber link we have built a low-noise optical fiber interferometer and investigated noise sources that affect the overall performance of the optical link. The frequency stability at the remote end has been measured using the clock laser of PTB's Yb+ frequency standard operating at 344 THz. We show that the frequency of a frequency-stabilized fiber laser can be transmitted over a total fiber length of 146 km with a relative frequency uncertainty below 1E-19, and short term frequency instability given by the fractional Allan deviation of sy(t)=3.3E-15/(t/s)

Genome-Wide Epistatic Interaction between DEF1B and APOL1 High-Risk Genotypes for Chronic Kidney Disease

CKD disproportionately affects Black and Hispanic/Latino individuals. APOL1 risk variants are common in individuals of recent African ancestry and explain some disparities. However, not all individuals with APOL1 high-risk genotypes develop CKD, suggesting gene-environment and gene-gene (epistatic) modifiers. Prior genetic studies studying single nucleotide polymorphism (SNP) interactions with APOL1 risk genotypes were limited by small sample sizes and did not identify genome-wide significant interactions. We conducted a genome-wide SNP-APOL1 interaction analysis using two large datasets with genetic and phenotypic data