2D core ion temperature and impurity density measurements with Coherence Imaging Charge Exchange Recombination Spectroscopy (CICERS) at Wendelstein 7-X (invited).

Coherence Imaging Charge Exchange Recombination Spectroscopy (CICERS) is an imaging diagnostic installed in Wendelstein 7-X from which 2D maps of ion temperature (Ti) and impurity density (nZ) are obtained. The improved spatial resolution and coverage, as compared to standard Charge eXchange Recombination Spectroscopy (CXRS), with which these parameters can be assessed, come at the expense of spectral resolution, requiring the development of new strategies to isolate the active charge exchange contribution from passive and Bremsstrahlung radiation. In this work, a new approach based on the modeling of background radiation is presented and applied to the derivation of 2D Ti maps. These are compared to the Ti profiles derived from standard CXRS, which found excellent agreement up to the edge (ρ > 0.8). The CICERS view is implemented in the pyFIDAsim code, which is used to provide further insight into the spatial localization of the radiation as measured by the diagnostic. Moreover, an absolute intensity calibration is carried out, and, coupled with pyFIDAsim, the first 2D nC maps are obtained and validated against CXRS data.

Visible core spectroscopy at Wendelstein 7-X.

This paper presents an overview of recent hardware extensions and data analysis developments to the Wendelstein 7-X visible core spectroscopy systems. These include upgrades to prepare the in-vessel components for long-pulse operation, nine additional spectrometers, a new line of sight array for passive spectroscopy, and a coherence imaging charge exchange spectroscopy diagnostic. Progress in data analysis includes ion temperatures and densities from multiple impurity species, a statistical comparison with x-ray crystal spectrometer measurements, neutral density measurements from thermal passive Balmer-alpha emission, and a Bayesian analysis of active hydrogen emission, which is able to infer electron density and main ion temperature profiles.

Charge exchange recombination spectroscopy on the alkali beam of Wendelstein 7-X.

Measurements of ion temperature profiles are required to assess the energy and particle transport processes in the Wendelstein 7-X stellarator. This device is equipped with a diagnostic alkali beam, which can be utilized to determine local impurity temperatures and densities by Charge Exchange Recombination Spectroscopy (CXRS). It could provide such profiles in the edge plasma, where other diagnostics are less efficient. With this contribution, first results of CXRS measurements on the sodium beam from the scientific operation phase OP2.1 are presented. The spectroscopic system was in commissioning phase lacking some of the final optical components. Thus, the aim of the diagnostics during this campaign was to explore the measurement capabilities. Based on the processed spectra, the prospects of C5+ and C6+ ion temperature and concentration measurements are discussed. The results indicate that with the final optical setup under installation, the diagnostics could provide ion temperature profiles in the edge with 3 mm radial resolution and at least 1 s temporal resolution.

Impact of Magnetic Field Configuration on Heat Transport in Stellarators and Heliotrons.

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization.

Bayesian inference of spatially resolved Zeff profiles from line integrated bremsstrahlung spectra.

In nuclear fusion research, the effective ion charge Zeff, which characterizes the overall content of impurities, can be experimentally derived from the plasma electron-ion bremsstrahlung, given the electron density ne and temperature Te. At Wendelstein 7-X, a multichannel near-infrared spectrometer is installed to collect the plasma bremsstrahlung along 27 lines of sight covering more than half the plasma cross section, which provides information on Zeff over the entire plasma radius. To infer spatially resolved Zeff profiles, a Bayesian model is developed in the Minerva framework. Zeff, ne, and Te profiles are modeled as Gaussian processes, whose smoothness is determined by hyperparameters. These profiles are transformed to fields in Cartesian coordinates, given the poloidal magnetic flux surfaces calculated by the variational moments equilibrium code. Given all these physical quantities, the model predicts line-of-sight integrals of near-infrared bremsstrahlung spectra. The model includes the predictive (forward) models of the interferometer, Thomson scattering system, and visible and near-infrared spectrometers. Given the observations of all these diagnostics, the posterior probability distribution of Zeff profiles is calculated and shown as an inference solution. The smoothness (gradient) of the profiles is optimally chosen by Bayesian Occam's razor. Furthermore, wall reflections can significantly pollute the measurements of the plasma bremsstrahlung, which leads to over-estimation of Zeff values in the edge region. In the first results presented in this work, this problem does not appear, and the posterior samples of Zeff profiles are overall plausible and consistent with Zeff values inferred, given the data from the single-channel visible spectrometer.

Correction and verification of x-ray imaging crystal spectrometer analysis on Wendelstein 7-X through x-ray ray tracing.

X-ray ray tracing is used to develop ion-temperature corrections for the analysis of the X-ray Imaging Crystal Spectrometer (XICS) used at Wendelstein 7-X (W7-X) and perform verification on the analysis methods. The XICS is a powerful diagnostic able to measure ion-temperature, electron-temperature, plasma flow, and impurity charge state densities. While these systems are relatively simple in design, accurate characterization of the instrumental response and validation of analysis techniques are difficult to perform experimentally due to the requirement of extended x-ray sources. For this reason, a ray tracing model has been developed that allows characterization of the spectrometer and verification of the analysis methods while fully considering the real geometry of the XICS system and W7-X plasma. Through the use of ray tracing, several important corrections have been found that must be accounted for in order to accurately reconstruct the ion-temperature profiles. The sources of these corrections are described along with their effect on the analyzed profiles. The implemented corrections stem from three effects: (1) effect of sub-pixel intensity distribution during de-curving and spatial binning, (2) effect of sub-pixel intensity distribution during forward model evaluation and generation of residuals, and (3) effect of defocus and spherical aberrations on the instrumental response. Possible improvements to the forward model and analysis procedures are explored, along with a discussion of trade-offs in terms of computational complexity. Finally, the accuracy of the tomographic inversion technique in stellarator geometry is investigated, providing for the first time a verification exercise for inversion accuracy in stellarator geometry and a complete XICS analysis tool-chain.

Turbulence Mechanisms of Enhanced Performance Stellarator Plasmas.

We theoretically assess two mechanisms thought to be responsible for the enhanced performance observed in plasma discharges of the Wendelstein 7-X stellarator experiment fueled by pellet injection. The effects of the ambipolar radial electric field and the electron density peaking on the turbulent ion heat transport are separately evaluated using large-scale gyrokinetic simulations. The essential role of the stellarator magnetic geometry is demonstrated, by comparison with a tokamak.

Charge exchange recombination spectroscopy at Wendelstein 7-X.

The Charge Exchange Recombination Spectroscopy (CXRS) diagnostic has become a routine diagnostic on almost all major high temperature fusion experimental devices. For the optimized stellarator Wendelstein 7-X (W7-X), a highly flexible and extensive CXRS diagnostic has been built to provide high-resolution local measurements of several important plasma parameters using the recently commissioned neutral beam heating. This paper outlines the design specifics of the W7-X CXRS system and gives examples of the initial results obtained, including typical ion temperature profiles for several common heating scenarios, toroidal flow and radial electric field derived from velocity measurements, beam attenuation via beam emission spectra, and normalized impurity density profiles under some typical plasma conditions.

A divertor scraper observation system for the Wendelstein 7-X stellarator.

Two graphite divertor elements called scrapers have been installed on the Wendelstein 7-X stellarator in the throat of the magnetic island divertor. To diagnose one, we have designed, built, calibrated, and installed a new infrared/visible imaging endoscope system to enable detailed observations of the plasma interactions and heat loads at one of the scrapers and the nearby divertor surfaces. The new system uses a shuttered pinhole-protected pair of 90° off-axis 228 mm focal length aluminum parabolic mirrors, and two flat turning metal mirrors, to send light to a sapphire vacuum window 1.6 meters away, beyond which we have co-located telephoto lens-based infrared and visible cameras. The back-to-back off-axis parabolas serve to cancel out most aberrations, enabling the use of off-the-shelf commercial optics outside of the vessel. For the infrared, we use a 3-5 µm 1-megapixel FLIR SC8303HD camera and for the visible, a 5-megapixel CMOS PCO 5.5 edge camera. A short 1-m quartz pickoff fiber is used to send 200-1100 nm light to a compact spectrometer, also located in the same iron shield box as the cameras. The camera field of view covers the 700 mm length of the scraper, and includes locations monitored by thermocouples and Langmuir probes embedded in some of the scraper tiles. Predicted and actual optical test performances of the overall system are compared.

Overview of diagnostic performance and results for the first operation phase in Wendelstein 7-X (invited).

Wendelstein 7-X, a superconducting optimized stellarator built in Greifswald/Germany, started its first plasmas with the last closed flux surface (LCFS) defined by 5 uncooled graphite limiters in December 2015. At the end of the 10 weeks long experimental campaign (OP1.1) more than 20 independent diagnostic systems were in operation, allowing detailed studies of many interesting plasma phenomena. For example, fast neutral gas manometers supported by video cameras (including one fast-frame camera with frame rates of tens of kHz) as well as visible cameras with different interference filters, with field of views covering all ten half-modules of the stellarator, discovered a MARFE-like radiation zone on the inboard side of machine module 4. This structure is presumably triggered by an inadvertent plasma-wall interaction in module 4 resulting in a high impurity influx that terminates some discharges by radiation cooling. The main plasma parameters achieved in OP1.1 exceeded predicted values in discharges of a length reaching 6 s. Although OP1.1 is characterized by short pulses, many of the diagnostics are already designed for quasi-steady state operation of 30 min discharges heated at 10 MW of ECRH. An overview of diagnostic performance for OP1.1 is given, including some highlights from the physics campaigns.

Imaging motional Stark effect measurements at ASDEX Upgrade.

This paper presents an overview of results from the Imaging Motional Stark Effect (IMSE) diagnostic obtained during its first measurement campaign at ASDEX Upgrade since installation as a permanent diagnostic. A brief overview of the IMSE technique is given, followed by measurements of a standard H-mode discharge, which are compared to equilibrium reconstructions showing good agreement where expected. The development of special discharges for the calibration of pitch angle is reported and safety factor profile changes during sawteeth crashes are shown, which can be resolved to a few percent due to the high sensitivity at good time resolution of the new IMSE system.

The prototype imaging motional Stark effect diagnostic for ASDEX upgrade.

This paper presents the development and testing of the prototype Imaging Motional Stark-Effect (IMSE) diagnostic, designed for ASDEX upgrade. A detailed description of the core hardware, theory of operation, and application to complex MSE spectra are presented and analytical evaluation methods suitable for the required accuracy are developed. The diagnostic is tested with a MSE-like polarised spectrum to assess the accuracy of different modulation modes suggested in previous works. Each is found to have small systematic errors due to non-ideal effects of the components, which must be carefully examined. In particular, the effect of intrinsic contrast that results from imperfect parallelism of the birefringent plates is found to have a strong effect. Methods to mitigate and correct for this are discussed. With the necessary corrections and calibrations, the accuracy of polarisation orientation is shown to be within ±0.2°. The effect of finite ellipticity is examined and the possibility to measure this to an accuracy of ±2.0° is demonstrated. The system is shown to be insensitive to broadband polarised background light, temperature variations, and critically to variations in the details of the MSE spectrum.

Fringe jump analysis and implementation of polarimetry on the ASDEX Upgrade DCN interferometer.

The ASDEX Upgrade tokamak is equipped with a 5-channel DCN interferometer with a probing wavelength of 195 µm. Up to now, phase measurement and density calculation have been accomplished by hard-wired phase counting electronics. Meanwhile, a fast digitizer has been installed which acquires the raw signals. That way, the various causes of counting errors by integer multiples of 2π, so-called fringe jumps, can be analyzed, and phase reconstruction schemes based on digital signal processing can be developed. In addition, a prototype polarimeter setup has been installed on one channel and allows for measurement of the Faraday rotation experienced by the probing beam.

Mechanism of androgen receptor corepression by CKßBP2/CRIF1, a multifunctional transcription factor coregulator expressed in prostate cancer.

The transcription factor coregulator Casein kinase IIß-binding protein 2 or CR6-interacting factor 1 (CKßBP2/CRIF1) binds the androgen receptor (AR) in prostate cancer cells and in response to dihydrotestosterone localizes with AR on the prostate-specific antigen gene enhancer, but does not bind DNA suggesting CKßBP2/CRIF1 localization in chromatin is determined by AR. In this study we show also that CKßBP2/CRIF1 inhibits wild-type AR and AR N-terminal transcriptional activity, binds to the AR C-terminal region, inhibits interaction of the AR N- and C-terminal domains (N/C interaction) and competes with p160 coactivator binding to the AR C-terminal domain, suggesting CKßBP2/CRIF1 interferes with AR activation functions 1 and 2. CKßBP2/CRIF1 is expressed mainly in stromal cells of benign prostatic hyperplasia and in stroma and epithelium of prostate cancer. CKßBP2/CRIF1 protein is increased in epithelium of androgen-dependent prostate cancer compared to benign prostatic hyperplasia and decreased slightly in castration recurrent epithelium compared to androgen-dependent prostate cancer. The multifunctional CKßBP2/CRIF1 is a STAT3 interacting protein and reported to be a coactivator of STAT3. CKßBP2/CRIF1 is expressed with STAT3 in prostate cancer where STAT3 may help to offset the AR repressor effect of CKßBP2/CRIF1 and allow AR regulation of prostate cancer growth.

14-3-3{eta} Amplifies Androgen Receptor Actions in Prostate Cancer.

PURPOSE: Androgen receptor abundance and androgen receptor-regulated gene expression in castration-recurrent prostate cancer are indicative of androgen receptor activation in the absence of testicular androgen. Androgen receptor transactivation of target genes in castration-recurrent prostate cancer occurs in part through mitogen signaling that amplifies the actions of androgen receptor and its coregulators. Herein we report on the role of 14-3-3eta in androgen receptor action. Experimental Design and RESULTS: Androgen receptor and 14-3-3eta colocalized in COS cell nuclei with and without androgen, and 14-3-3eta promoted androgen receptor nuclear localization in the absence of androgen. 14-3-3eta interacted with androgen receptor in cell-free binding and coimmunoprecipitation assays. In the recurrent human prostate cancer cell line, CWR-R1, native endogenous androgen receptor transcriptional activation was stimulated by 14-3-3eta at low dihydrotestosterone concentrations and was increased by epidermal growth factor. Moreover, the dihydrotestosterone- and epidermal growth factor-dependent increase in androgen receptor transactivation was inhibited by a dominant negative 14-3-3eta. In the CWR22 prostate cancer xenograft model, 14-3-3eta expression was increased by androgen, suggesting a feed-forward mechanism that potentiates both 14-3-3eta and androgen receptor actions. 14-3-3eta mRNA and protein decreased following castration of tumor-bearing mice and increased in tumors of castrate mice after treatment with testosterone. CWR22 tumors that recurred 5 months after castration contained 14-3-3eta levels similar to the androgen-stimulated tumors removed before castration. In a human prostate tissue microarray of clinical specimens, 14-3-3eta localized with androgen receptor in nuclei, and the similar amounts expressed in castration-recurrent prostate cancer, androgen-stimulated prostate cancer, and benign prostatic hyperplasia were consistent with androgen receptor activation in recurrent prostate cancer. CONCLUSION: 14-3-3eta enhances androgen- and mitogen-induced androgen receptor transcriptional activity in castration-recurrent prostate cancer. (Clin Cancer Res 2009;15(24):7571-81).

Comparison of ACINUS, caspase-3, and TUNEL as apoptotic markers in determination of tumor growth rates of clinically localized prostate cancer using image analysis.

BACKGROUND: The balance between apoptotic and proliferative processes determines the enlargement of a tumor. Accurate measurement of apoptotic and proliferative rates from diagnostic prostate biopsies would allow calculation of tumor growth rates in a population-based prostate cancer (CaP) study. Automated image analysis may be used if proliferation and apoptotic biomarkers provide clearly resolved immunostained images. METHODS: Clinical CaP aggressiveness was assigned as low, intermediate or high using clinical criteria for 46 research subjects with newly diagnosed CaP. Diagnostic biopsy sections from the research subjects were dual-labeled for proliferation biomarker, Ki-67 and apoptotic biomarker, apoptotic chromatin condensation inducer in the nucleus (ACINUS). Apoptotic biomarkers, caspase-3 and terminal deoxyribonucleotidyltransferase mediated dUTP-biotin nick end labeling (TUNEL) were labeled separately. Images from immunostained sections were analyzed using automated image analysis and tumor growth rates computed. Association between clinical CaP aggressiveness and tumor growth rates was explored. RESULTS: Sixteen subjects had high, 17 had intermediate, and 13 had low clinical CaP aggressiveness. Positive immunostaining was localized to the nucleus for Ki-67, ACINUS, and TUNEL. A statistically significant linear trend across clinical CaP aggressiveness categories was found when tumor growth rates were calculated using ACINUS (P = 0.046). Logistic regression and ROC plots generated showed ACINUS (AUC = 0.677, P = 0.048) and caspase-3 (AUC = 0.694, P = 0.038) to be better predictors than TUNEL (AUC = 0.669, P = 0.110). CONCLUSIONS: ACINUS met the criteria for automated image analysis and for calculation of apoptotic rate. Tumor growth rates determined using automated image analysis should be evaluated for clinical prediction of CaP aggressiveness, treatment response, recurrence, and mortality.

Feasibility of constructing tissue microarrays from diagnostic prostate biopsies.

OBJECTIVES: The ability to construct prostate tissue microarrays (TMAs) using prostate needle biopsies could allow high throughput molecular profiling to search for prostate cancer prognostic biomarkers. MATERIALS AND METHODS: Diagnostic prostate biopsies from 13 patients (diagnosed 1996-2000) were obtained from the University of North Carolina (UNC) to construct one prostate TMA under uniform conditions. A second prostate TMA was attempted using diagnostic prostate biopsies from 45 patients (diagnosed 2004) obtained from the North Carolina-Louisiana Prostate Cancer Project (PCaP). RESULTS: Eleven men had sufficient prostate cancer in their diagnostic prostate biopsy blocks to construct a UNC TMA that yielded six-micron sections that provided an average of 76% of cores (maximum 99%) to a depth of 360 microm. Diagnostic prostate biopsy blocks from 35 PCaP research subjects were unsuitable for TMA construction as a result of no remaining prostate cancer in 4, insufficient prostate cancer in 9, and insufficient prostate tissue in 22. The PCaP TMA constructed from 10 men yielded an average of 37%, and a maximum of 45%, of cores when sectioned to a depth of 360 microm. CONCLUSIONS: TMAs may be constructed from diagnostic prostate biopsies obtained at an academic center under uniform conditions. However, excessive facing of blocks and the large number of re-cuts ordered by many community pathology laboratories deplete diagnostic prostate biopsy tissue. The experience of a population-based study of men with newly diagnosed prostate cancer in Louisiana and North Carolina suggests that TMAs may not be constructed using diagnostic prostate biopsies from men diagnosed with prostate cancer throughout the United States.

Progesterone for Premenstrual Syndrome.

BACKGROUND: Premenstrual Syndrome (PMS) is the term for severe symptoms experienced by about 5% of menstruating women up to two weeks before their menstrual periods, but not at other times. Treatment with progesterone may restore a deficiency, or balance the level of progesterone with other menstrual hormones. Progesterone therapy may reduce the effects of falling progesterone levels on the brain or on electrolytes in the blood. OBJECTIVES: The objectives were to determine if progesterone has been found to be an effective treatment for all or some premenstrual symptoms, and if adverse events associated with this treatment have been reported. SEARCH STRATEGY: We last searched the Cochrane Menstrual Disorders and Subfertility Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2005), MEDLINE (1966 to 2005) and EMBASE (1980 to 2005) in March 2005, and PsycINFO (1806 to 2006) in April 2006. We contacted pharmaceutical companies for information about unpublished trials. SELECTION CRITERIA: We included randomised double-blind, placebo-controlled trials of progesterone on women with PMS diagnosed by at least two prospective cycles, without current psychiatric disorder. DATA COLLECTION AND ANALYSIS: Two reviewers (BM and OF) extracted data independently, and decided on the trials to be included. OF wrote to the trial investigators to ask for missing data. MAIN RESULTS: We considered 17 studies. We included two trials totaling 280 participants aged from 18 to 45 years. Of these 115 yielded analysable results. Both studies measured outcomes using subjective scales of symptom severity but made calculations as if they were interval data. The two studies differed in design, participants, dose of progesterone, how and when the dose was administered and in outcome measures. It was impossible to combine data in a meta-analysis. Adverse events which may or may not have been the side effects of the treatment, were generally described as mild. Both trials intended to exclude women whose symptoms continued after their periods; unfortunately the larger multicentre study had some ineligible participants. Overall, participants benefited more from progesterone than placebo. This was statistically significant in per protocol analysis but not in the intention-to-treat analysis, except for the first cycle. The smaller, crossover study found no statistically significant difference between oral progesterone, vaginally absorbed progesterone and placebo. AUTHORS' CONCLUSIONS: We could not say that progesterone helped women with PMS, nor that it was ineffective. Neither trial distinguished a subgroup of women who benefited.