Trap-integrated fluorescence detection with silicon photomultipliers for sympathetic laser cooling in a cryogenic Penning trap.

We present a fluorescence-detection system for laser-cooled 9Be+ ions based on silicon photomultipliers (SiPMs) operated at 4 K and integrated into our cryogenic 1.9 T multi-Penning-trap system. Our approach enables fluorescence detection in a hermetically sealed cryogenic Penning-trap chamber with limited optical access, where state-of-the-art detection using a telescope and photomultipliers at room temperature would be extremely difficult. We characterize the properties of the SiPM in a cryocooler at 4 K, where we measure a dark count rate below 1 s-1 and a detection efficiency of 2.5(3)%. We further discuss the design of our cryogenic fluorescence-detection trap and analyze the performance of our detection system by fluorescence spectroscopy of 9Be+ ion clouds during several runs of our sympathetic laser-cooling experiment.

BASE-STEP: A transportable antiproton reservoir for fundamental interaction studies.

Currently, the world's only source of low-energy antiprotons is the AD/ELENA facility located at CERN. To date, all precision measurements on single antiprotons have been conducted at this facility and provide stringent tests of fundamental interactions and their symmetries. However, magnetic field fluctuations from the facility operation limit the precision of upcoming measurements. To overcome this limitation, we have designed the transportable antiproton trap system BASE-STEP to relocate antiprotons to laboratories with a calm magnetic environment. We anticipate that the transportable antiproton trap will facilitate enhanced tests of charge, parity, and time-reversal invariance with antiprotons and provide new experimental possibilities of using transported antiprotons and other accelerator-produced exotic ions. We present here the technical design of the transportable trap system. This includes the transportable superconducting magnet, the cryogenic inlay consisting of the trap stack and detection systems, and the differential pumping section to suppress the residual gas flow into the cryogenic trap chamber.

Ultra-thin polymer foil cryogenic window for antiproton deceleration and storage.

We present the design and characterization of a cryogenic window based on an ultra-thin aluminized biaxially oriented polyethylene terephthalate foil at T < 10 K, which can withstand a pressure difference larger than 1 bar at a leak rate <1×10-9 mbar l/s. Its thickness of ∼1.7 µm makes it transparent to various types of particles over a broad energy range. To optimize the transfer of 100 keV antiprotons through the window, we tested the degrading properties of different aluminum coated polymer foils of thicknesses between 900 and 2160 nm, concluding that 1760 nm foil decelerates antiprotons to an average energy of 5 keV. We have also explicitly studied the permeation as a function of coating thickness and temperature and have performed extensive thermal and mechanical endurance and stress tests. Our final design integrated into the experiment has an effective open surface consisting of seven holes with a diameter of 1 mm and will transmit up to 2.5% of the injected 100 keV antiproton beam delivered by the Antiproton Decelerator and Extra Low ENergy Antiproton ring facility of CERN.

BASE-high-precision comparisons of the fundamental properties of protons and antiprotons.

Abstract: The BASE collaboration at the antiproton decelerator/ELENA facility of CERN compares the fundamental properties of protons and antiprotons with ultra-high precision. Using advanced Penning trap systems, we have measured the proton and antiproton magnetic moments with fractional uncertainties of 300 parts in a trillion (p.p.t.) and 1.5 parts in a billion (p.p.b.), respectively. The combined measurements improve the resolution of the previous best test in that sector by more than a factor of 3000. Very recently, we have compared the antiproton/proton charge-to-mass ratios with a fractional precision of 16 p.p.t., which improved the previous best measurement by a factor of 4.3. These results allowed us also to perform a differential matter/antimatter clock comparison test to limits better than 3%. Our measurements enable us to set limits on 22 coefficients of CPT- and Lorentz-violating standard model extensions (SME) and to search for potentially asymmetric interactions between antimatter and dark matter. In this article, we review some of the recent achievements and outline recent progress towards a planned improved measurement of the antiproton magnetic moment with an at least tenfold improved fractional accuracy.

A high-Q superconducting toroidal medium frequency detection system with a capacitively adjustable frequency range >180 kHz.

We describe a newly developed polytetrafluoroethylene/copper capacitor driven by a cryogenic piezoelectric slip-stick stage and demonstrate with the chosen layout cryogenic capacitance tuning of ≈60 pF at ≈10 pF background capacitance. Connected to a highly sensitive superconducting toroidal LC circuit, we demonstrate tuning of the resonant frequency between 345 and 685 kHz, at quality factors Q > 100 000. Connected to a cryogenic ultra low noise amplifier, a frequency tuning range between 520 and 710 kHz is reached, while quality factors Q > 86 000 are achieved. This new device can be used as a versatile image current detector in high-precision Penning-trap experiments or as an LC-circuit-based haloscope detector to search for the conversion of axion-like dark matter to radio-frequency photons. This new development increases the sensitive detection bandwidth of our axion haloscope by a factor of ≈1000.

A new benchmark of soft X-ray transition energies of Ne , CO 2 , and SF 6 : paving a pathway towards ppm accuracy.

Abstract: A key requirement for the correct interpretation of high-resolution X-ray spectra is that transition energies are known with high accuracy and precision. We investigate the K-shell features of Ne , CO 2 , and SF 6 gases, by measuring their photo ion-yield spectra at the BESSY II synchrotron facility simultaneously with the 1s-np fluorescence emission of He-like ions produced in the Polar-X EBIT. Accurate ab initio calculations of transitions in these ions provide the basis of the calibration. While the CO 2 result agrees well with previous measurements, the SF 6 spectrum appears shifted by ∼ 0.5 eV, about twice the uncertainty of the earlier results. Our result for Ne shows a large departure from earlier results, but may suffer from larger systematic effects than our other measurements. The molecular spectra agree well with our results of time-dependent density functional theory. We find that the statistical uncertainty allows calibrations in the desired range of 1-10 meV, however, systematic contributions still limit the uncertainty to ∼ 40-100 meV, mainly due to the temporal stability of the monochromator energy scale. Combining our absolute calibration technique with a relative energy calibration technique such as photoelectron energy spectroscopy will be necessary to realize its full potential of achieving uncertainties as low as 1-10 meV.

Effects of prescribed fire timing on grazing performance of yearling beef cattle, forage biomass accumulation, and plant community characteristics on native tallgrass prairie in the Kansas Flint Hills.

Recent research demonstrated that mid- or late-summer prescribed fires can be employed to manage sericea lespedeza (Lespedeza cuneata) infestations in the Kansas Flint Hills. The effects of prescribed fire applied during the growing season (i.e., August to October) on grazing performance of yearling cattle have not been evaluated. Native pastures (n = 18; 22 ± 4.0 ha) were grouped by watershed and assigned randomly to one of three prescribed-fire treatments: spring (7 April ± 2.1 d), summer (21 August ± 5.7 d), or autumn (2 October ± 9.9 d). Yearling beef cattle were grazed from May to August at a targeted stocking density of 280 kg live-weight/ha following prescribed-fire application. Forage biomass accumulations, soil cover, plant species composition, and root carbohydrate concentrations in four native plant species were evaluated. Total body weight (BW) gains and average daily gain were greater (P = 0.01) for cattle that grazed the spring and summer prescribed-fire treatments compared with those that grazed the autumn prescribed-fire treatment. As a result, final BW were greater (P = 0.04) in the spring and summer treatments than the autumn treatment. Conversely, forage biomass accumulations did not differ (P = 0.91) between fire regimes. Proportions of bare soil were greater (P < 0.01) in the spring treatment compared with the summer and autumn treatments, whereas proportions of litter on the soil surface were greater (P < 0.01) in summer- and autumn-burned pastures compared with spring-burned pastures. Total basal cover of graminoids and forbs did not differ (P ≤ 0.15) between prescribed fire treatments. Likewise, total basal cover of C3 or C4 perennial grasses did not differ (P ≥ 0.23) between prescribed-fire treatments. No treatment differences (P = 0.24) in root starch or root water-soluble carbohydrate concentrations in big bluestem (Andropogon gerardii), little bluestem (Schizachyrium scoparium), Indiangrass (Sorghastrum nutans), or purple prairieclover (Dalea purpurea) were detected. These data were interpreted to suggest that summer or autumn prescribed fire can be applied without reducing forage biomass accumulations, root carbohydrate concentrations in key native plant species, or considerably altering native plant populations compared with conventional spring-season prescribed fire; however, summer prescribed fire could be favored over spring or autumn prescribed fire both to maintain stocker cattle growth performance and to achieve control over sericea lespedeza.

An ultralow-noise superconducting radio-frequency ion trap for frequency metrology with highly charged ions.

We present a novel ultrastable superconducting radio-frequency (RF) ion trap realized as a combination of an RF cavity and a linear Paul trap. Its RF quadrupole mode at 34.52 MHz reaches a quality factor of Q ≈ 2.3 × 105 at a temperature of 4.1 K and is used to radially confine ions in an ultralow-noise pseudopotential. This concept is expected to strongly suppress motional heating rates and related frequency shifts that limit the ultimate accuracy achieved in advanced ion traps for frequency metrology. Running with its low-vibration cryogenic cooling system, electron-beam ion trap, and deceleration beamline supplying highly charged ions (HCIs), the superconducting trap offers ideal conditions for optical frequency metrology with ionic species. We report its proof-of-principle operation as a quadrupole-mass filter with HCIs and trapping of Doppler-cooled 9Be+ Coulomb crystals.

Coherent laser spectroscopy of highly charged ions using quantum logic.

Precision spectroscopy of atomic systems1 is an invaluable tool for the study of fundamental interactions and symmetries2. Recently, highly charged ions have been proposed to enable sensitive tests of physics beyond the standard model2-5 and the realization of high-accuracy atomic clocks3,5, owing to their high sensitivity to fundamental physics and insensitivity to external perturbations, which result from the high binding energies of their outer electrons. However, the implementation of these ideas has been hindered by the low spectroscopic accuracies (of the order of parts per million) achieved so far6-8. Here we cool trapped, highly charged argon ions to the lowest temperature reported so far, and study them using coherent laser spectroscopy, achieving an increase in precision of eight orders of magnitude. We use quantum logic spectroscopy9,10 to probe the forbidden optical transition in 40Ar13+ at a wavelength of 441 nanometres and measure its excited-state lifetime and g-factor. Our work unlocks the potential of highly charged ions as ubiquitous atomic systems for use in quantum information processing, as frequency standards and in highly sensitive tests of fundamental physics, such as searches for dark-matter candidates11 or violations of fundamental symmetries2.

High-Precision Determination of Oxygen K_{α} Transition Energy Excludes Incongruent Motion of Interstellar Oxygen.

We demonstrate a widely applicable technique to absolutely calibrate the energy scale of x-ray spectra with experimentally well-known and accurately calculable transitions of highly charged ions, allowing us to measure the K-shell Rydberg spectrum of molecular O_{2} with 8 meV uncertainty. We reveal a systematic ∼450 meV shift from previous literature values, and settle an extraordinary discrepancy between astrophysical and laboratory measurements of neutral atomic oxygen, the latter being calibrated against the aforementioned O_{2} literature values. Because of the widespread use of such, now deprecated, references, our method impacts on many branches of x-ray absorption spectroscopy. Moreover, it potentially reduces absolute uncertainties there to below the meV level.

A cryogenic radio-frequency ion trap for quantum logic spectroscopy of highly charged ions.

A cryogenic radio-frequency ion trap system designed for quantum logic spectroscopy of highly charged ions (HCI) is presented. It includes a segmented linear Paul trap, an in-vacuum imaging lens, and a helical resonator. We demonstrate ground state cooling of all three modes of motion of a single 9Be+ ion and determine their heating rates as well as excess axial micromotion. The trap shows one of the lowest levels of electric field noise published to date. We investigate the magnetic-field noise suppression in cryogenic shields made from segmented copper, the resulting magnetic field stability at the ion position and the resulting coherence time. Using this trap in conjunction with an electron beam ion trap and a deceleration beamline, we have been able to trap single highly charged Ar13+ (Ar XIV) ions concurrently with single Be+ ions, a key prerequisite for the first quantum logic spectroscopy of a HCI. This major stepping stone allows us to push highly-charged-ion spectroscopic precision from the gigahertz to the hertz level and below.

Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non-small-cell lung cancer: The global, multicenter EXPRESS study.

OBJECTIVES: Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC. MATERIALS AND METHODS: Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). RESULTS: Of 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPS ≥ 50%, 1232 (52%) had PD-L1 TPS ≥ 1%, and 1136 (48%) had PD-L1 TPS < 1%. The most common reason for not having PD-L1 data (n = 249) was insufficient tumor cells (<100) on the slide (n = 170 [6%]). Percentages of patients with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively, were 27% and 53%. CONCLUSIONS: This is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPS ≥ 50% and TPS ≥ 1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations.

Closed-cycle, low-vibration 4 K cryostat for ion traps and other applications.

In vacuo cryogenic environments are ideal for applications requiring both low temperatures and extremely low particle densities. This enables reaching long storage and coherence times, for example, in ion traps, essential requirements for experiments with highly charged ions, quantum computation, and optical clocks. We have developed a novel cryostat continuously refrigerated with a pulse-tube cryocooler and providing the lowest vibration level reported for such a closed-cycle system with 1 W cooling power for a <5 K experiment. A decoupling system suppresses vibrations from the cryocooler by three orders of magnitude down to a level of 10 nm peak amplitudes in the horizontal plane. Heat loads of about 40 W (at 45 K) and 1 W (at 4 K) are transferred from an experimental chamber, mounted on an optical table, to the cryocooler through a vacuum-insulated massive 120 kg inertial copper pendulum. The 1.4 m long pendulum allows installation of the cryocooler in a separate, acoustically isolated machine room. At the experimental chamber, we measured the residual vibrations using an interferometric setup. The positioning of the 4 K elements is reproduced to better than a few micrometer after a full thermal cycle to room temperature. Extreme high vacuum on the 10-15 mbar level is achieved. In collaboration with the Max-Planck-Institut für Kernphysik, such a setup is now in operation at the Physikalisch-Technische Bundesanstalt for a next-generation optical clock experiment using highly charged ions.

Production of highly charged ions of rare species by laser-induced desorption inside an electron beam ion trap.

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 165Ho from samples of only 1012 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 163Ho for a high-precision measurement of the QEC-value of the electron capture in 163Ho 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.

The Heidelberg compact electron beam ion traps.

Electron beam ion traps (EBITs) are ideal tools for both production and study of highly charged ions (HCIs). In order to reduce their construction, maintenance, and operation costs, we have developed a novel, compact, room-temperature design, the Heidelberg Compact EBIT (HC-EBIT). Four already commissioned devices operate at the strongest fields (up to 0.86 T) reported for such EBITs using permanent magnets, run electron beam currents up to 80 mA, and energies up to 10 keV. They demonstrate HCI production, trapping, and extraction of pulsed Ar16+ bunches and continuous 100 pA ion beams of highly charged Xe up to charge state 29+, already with a 4 mA, 2 keV electron beam. Moreover, HC-EBITs offer large solid-angle ports and thus high photon count rates, e.g., in x-ray spectroscopy of dielectronic recombination in HCIs up to Fe24+, achieving an electron-energy resolving power of E/ΔE > 1500 at 5 keV. Besides traditional on-axis electron guns, we have also implemented a novel off-axis gun for laser, synchrotron, and free-electron laser applications, offering clear optical access along the trap axis. We report on its first operation at a synchrotron radiation facility demonstrating the resonant photoexcitation of highly charged oxygen.

Coulomb crystallization of highly charged ions.

Control over the motional degrees of freedom of atoms, ions, and molecules in a field-free environment enables unrivalled measurement accuracies but has yet to be applied to highly charged ions (HCIs), which are of particular interest to future atomic clock designs and searches for physics beyond the Standard Model. Here, we report on the Coulomb crystallization of HCIs (specifically (40)Ar(13+)) produced in an electron beam ion trap and retrapped in a cryogenic linear radiofrequency trap by means of sympathetic motional cooling through Coulomb interaction with a directly laser-cooled ensemble of Be(+) ions. We also demonstrate cooling of a single Ar(13+) ion by a single Be(+) ion-the prerequisite for quantum logic spectroscopy with a potential 10(-19) accuracy level. Achieving a seven-orders-of-magnitude decrease in HCI temperature starting at megakelvin down to the millikelvin range removes the major obstacle for HCI investigation with high-precision laser spectroscopy.

Targeted resequencing of candidate genes using selector probes.

Targeted genome enrichment is a powerful tool for making use of the massive throughput of novel DNA-sequencing instruments. We herein present a simple and scalable protocol for multiplex amplification of target regions based on the Selector technique. The updated version exhibits improved coverage and compatibility with next-generation-sequencing (NGS) library-construction procedures for shotgun sequencing with NGS platforms. To demonstrate the performance of the technique, all 501 exons from 28 genes frequently involved in cancer were enriched for and sequenced in specimens derived from cell lines and tumor biopsies. DNA from both fresh frozen and formalin-fixed paraffin-embedded biopsies were analyzed and 94% specificity and 98% coverage of the targeted region was achieved. Reproducibility between replicates was high (R(2) = 0, 98) and readily enabled detection of copy-number variations. The procedure can be carried out in <24 h and does not require any dedicated instrumentation.

TGF-ß signaling in gingival fibroblast-epithelial interaction.

The underlying mechanism and the therapeutic regimen for the transition of reversible gingivitis to irreversible periodontitis are unclear. Since transforming growth factor (TGF)-ß has been implicated in differentially regulated gene expression in gingival fibroblasts, we hypothesized that TGF-ß signaling is activated in periodontitis-affected gingiva, along with enhanced collagen degradation, that is reversed by TGF-ß inhibition. A novel three-dimensional (3D) gel-culture system consisting of primary human gingival fibroblasts (GF) and gingival epithelial (GE) cells in collagen gels was applied. GF populations from patients with severe periodontitis degraded collagen gels, which was reduced by TGF-ß-receptor kinase inhibition. Up-regulation of TGF-ß-responsive genes was evident in GF/GE co-cultures. Furthermore, the TGF-ß downstream transducer Smad3C was highly phosphorylated in periodontitis-affected gingiva and 3D cultures. These results imply that TGF-ß signaling is involved in fibroblast-epithelial cell interaction in periodontitis, and suggest that the 3D culture system is a useful in vitro model for therapeutic drug screening for periodontitis.

Complementary and alternative medicine in lung cancer patients: a neglected phenomenon?

Study on the use of complementary and alternative medicine (CAM) in lung cancer patients has been widely neglected. Therefore, we initiated a study on the use of CAM in lung cancer patients in addition to radiation treatment. Overall, 120 patients from 3 institutions were interviewed by a standardized questionnaire. Besides the tumor parameters and the use of CAM, the reason for the use, patient information of the medication, the information sources and the subjective condition of the patient. Altogether, 54% of the patients reported using CAM (66% of female patients, 52% of male patients). The most frequently used CAM measures were vitamin combinations (17%), mistletoe (15%), and selenium (12%). A total of 52% reported the wish to support the tumor treatment as a reason for using CAM and 27% had a 'better feeling' using CAM. 50% of CAM was bought by the patients themselves and 50% were prescribed by their family physicians. The use of CAM is frequent in lung cancer patients. Our results suggest that it is very important to obtain information on the CAM use of patients and, particularly in controlled clinical trials, to prospectively document it.

Cytokine profile in synovial fluid from patients with internal derangement of the temporomandibular joint: a preliminary study.

OBJECTIVES: Temporomandibular joint disorders (TMD) comprise a group of chronic painful conditions of mastication in the temporomandibular joint (TMJ). Although the association between TMD and internal derangement of the TMJ is well documented, the functional relevance is still unclear. Increased concentrations of inflammatory mediators have been identified in the synovial fluid of affected patients with TMD, suggesting an underlying degenerative or inflammatory process. The aim of this study was to generate a comprehensive cytokine expression profile in TMD. METHODS: 15 samples from patients with internal derangement of TMJ were analysed using a novel cytokine array that enables the analysis of 79 different cytokines simultaneously. RESULTS: Cytokine levels were correlated with the presence of joint effusion (JE) determined by MRI. In the majority of synovial fluid samples, angiogenin (Ang), fibroblast growth factor (FGF)-9, insulin-like growth factor-binding protein (IGFBP)-3, interleukin (IL)-1alpha, IL-1beta, IL-8, inducible protein (IP)-10, macrophage inflammatory protein (MIP)-1beta, osteoprotegerin (OPG), transforming growth factor (TGF)-beta2, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, tumour necrosis factor (TNF)-beta and vascular endothelial growth factor (VEGF) were detectable. Furthermore, the expression levels of Ang, brain-derived neurotrophic factor (BDNF), FGF-4, FGF-9, IGFBP-2, IL-8, MIP-1beta, OPG, pulmonary and activation-regulated protein (PARC), TGF-beta2, TIMP-2 and VEGF were significantly associated with the presence of JE; among these, nine cytokines (Ang, BDNF, FGF-4, FGF-9, IGFBP-2, MIP-1beta, PARC, TGF-beta2 and TIMP-2) were hitherto not described in TMD. CONCLUSIONS: This study confirmed previous reports of elevated cytokine levels in TMD. Additionally, we identified previously undescribed cytokines that were upregulated and correlated significantly with the presence of JE. We were able to identify novel cytokines that have hitherto not been described in TMD. Strategies targeting the identified cytokines may represent a novel therapy option in TMD.