Experimental and theoretical investigation of a multi-mode cooling scheme using multiple EIT resonances

We introduce and demonstrate double-bright electromagnetically induced transparency (D-EIT) cooling as a novel approach to EIT cooling. By involving an additional ground state, two bright states can be shifted individually into resonance for cooling of motional modes of frequencies that may be separated by more than the width of a single EIT cooling resonance. This allows three-dimensional ground state cooling of a $^{40}$Ca$^+$ ion trapped in a linear Paul trap with a single cooling pulse. Measured cooling rates and steady-state mean motional quantum numbers for this D-EIT cooling are compared with those of standard EIT cooling as well as concatenated standard EIT cooling pulses for multi-mode cooling. Experimental results are compared to full density matrix calculations. We observe a failure of the theoretical description within the Lamb-Dicke regime that can be overcome by a time-dependent rate theory. Limitations of the different cooling techniques and possible extensions to multi-ion crystals are discussed.Comment: 18 pages, 13 figures. We have decided to merge the contents of our submission arXiv:1711.00738 with this paper into one comprehensive work. New titl

Precision spectroscopy by photon-recoil signal amplification

Precision spectroscopy of atomic and molecular ions offers a window to new physics, but is typically limited to species with a cycling transition for laser cooling and detection. Quantum logic spectroscopy has overcome this limitation for species with long-lived excited states. Here, we extend quantum logic spectroscopy to fast, dipole-allowed transitions and apply it to perform an absolute frequency measurement. We detect the absorption of photons by the spectroscopically investigated ion through the photon recoil imparted on a co-trapped ion of a different species, on which we can perform efficient quantum logic detection techniques. This amplifies the recoil signal from a few absorbed photons to thousands of fluorescence photons. We resolve the line center of a dipole-allowed transition in 40Ca+ to 1/300 of its observed linewidth, rendering this measurement one of the most accurate of a broad transition. The simplicity and versatility of this approach enables spectroscopy of many previously inaccessible species.Comment: 25 pages, 6 figures, 1 table, updated supplementary information, fixed typo

On-line estimation of local oscillator noise and optimisation of servo parameters in atomic clocks

For atomic frequency standards in which fluctuations of the local oscillator (LO) frequency are the dominant noise source, we examine the role of the the servo algorithm that predicts and corrects these frequency fluctuations. We derive the optimal linear prediction algorithm, showing how to measure the relevant spectral properties of the noise and optimise servo parameters while the standard is running, using only the atomic error signal. We find that, for realistic LO noise spectra, a conventional integrating servo with a properly chosen gain performs nearly as well as the optimal linear predictor. Using simple analytical models and numerical simulations, we establish optimum probe times as a function of clock atom number and of the dominant noise type in the local oscillator. We calculate the resulting LO-dependent scaling of achievable clock stability with atom number for product states as well as for maximally-correlated states.Alexander von Humboldt foundationEMPIREU/HORIZON 2020DFG/CRC/1128DFG/CRC/122

An Optical Atomic Clock Based on a Highly Charged Ion

Optical atomic clocks are the most accurate measurement devices ever constructed and have found many applications in fundamental science and technology. The use of highly charged ions (HCI) as a new class of references for highest accuracy clocks and precision tests of fundamental physics has long been motivated by their extreme atomic properties and reduced sensitivity to perturbations from external electric and magnetic fields compared to singly charged ions or neutral atoms. Here we present the first realisation of this new class of clocks, based on an optical magnetic-dipole transition in Ar$^{13+}$. Its comprehensively evaluated systematic frequency uncertainty of $2.2\times10^{-17}$ is comparable to that of many optical clocks in operation. From clock comparisons we improve by eight and nine orders of magnitude upon the uncertainties for the absolute transition frequency and isotope shift ($^{40}$Ar vs. $^{36}$Ar), respectively. These measurements allow us to probe the largely unexplored quantum electrodynamic nuclear recoil, presented as part of improved calculations of the isotope shift which reduce the uncertainty of previous theory by a factor of three. This work establishes forbidden optical transitions in HCI as references for cutting-edge optical clocks and future high-sensitivity searches for physics beyond the standard model.Comment: Main: 20 pages, 3 figures. Supplement: 19 pages, 2 figure

Guidelines for developing optical clocks with 10−1810^{-18} fractional frequency uncertainty

There has been tremendous progress in the performance of optical frequency standards since the first proposals to carry out precision spectroscopy on trapped, single ions in the 1970s. The estimated fractional frequency uncertainty of today's leading optical standards is currently in the $10^{-18}$ range, approximately two orders of magnitude better than that of the best caesium primary frequency standards. This exceptional accuracy and stability is resulting in a growing number of research groups developing optical clocks. While good review papers covering the topic already exist, more practical guidelines are needed as a complement. The purpose of this document is therefore to provide technical guidance for researchers starting in the field of optical clocks. The target audience includes national metrology institutes (NMIs) wanting to set up optical clocks (or subsystems thereof) and PhD students and postdocs entering the field. Another potential audience is academic groups with experience in atomic physics and atom or ion trapping, but with less experience of time and frequency metrology and optical clock requirements. These guidelines have arisen from the scope of the EMPIR project "Optical clocks with $1 imes 10^{-18}$ uncertainty" (OC18). Therefore, the examples are from European laboratories even though similar work is carried out all over the world. The goal of OC18 was to push the development of optical clocks by improving each of the necessary subsystems: ultrastable lasers, neutral-atom and single-ion traps, and interrogation techniques. This document shares the knowledge acquired by the OC18 project consortium and gives practical guidance on each of these aspects

Scaffold-Based (Matrigel™) 3D Culture Technique of Glioblastoma Recovers a Patient-like Immunosuppressive Phenotype

Conventional 2D cultures are commonly used in cancer research though they come with limitations such as the lack of microenvironment or reduced cell heterogeneity. In this study, we investigated in what respect a scaffold-based (Matrigel™) 3D culture technique can ameliorate the limitations of 2D cultures. NGS-based bulk and single-cell sequencing of matched pairs of 2D and 3D models showed an altered transcription of key immune regulatory genes in around 36% of 3D models, indicating the reoccurrence of an immune suppressive phenotype. Changes included the presentation of different HLA surface molecules as well as cellular stressors. We also investigated the 3D tumor organoids in a co-culture setting with tumor-infiltrating lymphocytes (TILs). Of note, lymphocyte-mediated cell killing appeared less effective in clearing 3D models than their 2D counterparts. IFN-γ release, as well as live cell staining and proliferation analysis, pointed toward an elevated resistance of 3D models. In conclusion, we found that the scaffold-based (Matrigel™) 3D culture technique affects the transcriptional profile in a subset of GBM models. Thus, these models allow for depicting clinically relevant aspects of tumor-immune interaction, with the potential to explore immunotherapeutic approaches in an easily accessible in vitro system

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts