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.

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.

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.

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.

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.

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.

Web apps for profile fitting and power balance analysis at Wendelstein 7-X.

Two novel web apps for W7-X are introduced: Profile Cooker and Power House. They are designed to streamline the workflow of profile fitting and power balance analysis while offering a graphical user interface that works in any common browser. This allows us to compile a comprehensive database of experimental power balance results. All fitting functions available in Profile Cooker are presented and compared on the basis of example profiles. The power balance equation assumed in Power House is established and its individual terms are discussed. The main focus of the power balance analysis is on the turbulent transport coefficients. A model for quick calculation of neutral beam power deposition based on experimental profiles is presented. Neoclassical root transition poses an issue for power balance analysis due to the uncertainty of the radial electric field. A global, neoclassical simulation with the code EUTERPE is performed for a set of experimental profiles to gain an understanding of the neoclassical root transition.

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.

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.

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.

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.

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.

Steroid 5alpha-reductase isozymes I and II in recurrent prostate cancer.

PURPOSE: Prostate cancer recurs during androgen deprivation therapy despite reduced circulating androgens. We showed that recurrent prostate cancer tissue has testosterone levels similar to androgen-stimulated benign prostate, whereas dihydrotestosterone levels were reduced 82% to 1.45 nmol/L, sufficient for androgen receptor activation. The altered testosterone/dihydrotestosterone ratio in recurrent prostate cancer suggests loss of 5alpha-reducing capability. The aim of this study was to characterize steroid 5alpha-reductase isozymes I (S5alphaRI) and II (S5alphaRII) in prostate tissues. EXPERIMENTAL DESIGN: A tissue microarray was constructed from 22 recurrent prostate cancer specimens and matched pairs of androgen-stimulated benign prostate and androgen-stimulated prostate cancer from 23 radical prostatectomy specimens. Immunoblots were constructed from eight recurrent prostate cancers, eight androgen-stimulated benign prostate, and eight androgen-stimulated prostate cancer specimens. Isozyme expression was examined in microarray sections and immunoblots using S5alphaRI and S5alphaRII polyclonal antibodies. Isozyme activities were measured in 12 recurrent prostate cancer, 12 androgen-stimulated benign prostate, and 12 androgen-stimulated prostate cancer specimens. RESULTS: Nuclear immunostaining exhibited higher S5alphaRI expression than S5alphaRII in recurrent prostate cancer, androgen-stimulated benign prostate, and androgen-stimulated prostate cancers (P < 0.0001); mean expression was 125, 150, and 115 for S5alphaRI versus 10, 29, and 37 for S5alphaRII, respectively. Cytoplasmic immunostaining was moderate and similar for both isozymes in the three tissue types (P > 0.05). Immunoblots confirmed immunohistochemistry; S5alphaRI was expressed in recurrent prostate cancer specimens and S5alphaRII was not detected. The activity of S5alphaRI (114.4 pmol/mg epithelial protein/minute) was 3.7-fold higher than S5alphaRII (30.7 pmol/mg epithelial protein/minute) in recurrent prostate cancer specimens. CONCLUSIONS: Expression levels and isozyme activity shifts from S5alphaRII toward S5alphaRI in recurrent prostate cancer. Dual inhibition of S5alphaRI and S5alphaRII should reduce dihydrotestosterone biosynthesis and may prevent or delay growth of recurrent prostate cancer.

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.

Protein kinase cepsilon has the potential to advance the recurrence of human prostate cancer.

Prostatic epithelial cells that are capable of surviving in the absence of androgenic steroids were found to express protein kinase Cepsilon (PKCepsilon), an oncogenic protein capable of promoting autocrine cell-signaling events. Gene transfer experiments demonstrated that PKCepsilon overexpression was sufficient to transform androgen-dependent LNCaP cells into an androgen-independent variant that rapidly initiated tumor growth in vivo in both intact and castrated male nude mice. This transformation was associated with an accelerated rate of androgen-independent LNCaP cell proliferation, resistance to apoptosis, hyperphosphorylation of the mitogen-activated protein kinase extracellular signal-regulated kinase and transcriptional repressor protein retinoblastoma, and increased expression of E2F-1 and other 5'-cap-dependent mRNAs, including the G(1) cyclins, c-myc, and caveolin-1. Coimmunoprecipitation experiments indicated that PKCepsilon was associated with members of the extracellular signal-regulated kinase signaling cascade and the scaffolding protein caveolin-1. Caveolin-1, produced by LNCaP cells overexpressing PKCepsilon, was released into the medium, possibly through a Golgi-independent route, and significant growth inhibition was observed when these cells were cultured in the presence of an anti-caveolin-1 antiserum. Finally, antisense experiments established that endogenous PKCepsilon plays an important role in regulating the growth and survival of androgen-independent prostate cancer cells. This study provides several independent lines of evidence supporting the hypothesis that PKCepsilon expression may be sufficient to maintain prostate cancer growth and survival after androgen ablation.

A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy.

The development and growth of prostate cancer depends on the androgen receptor and its high-affinity binding of dihydrotestosterone, which derives from testosterone. Most prostate tumors regress after therapy to prevent testosterone production by the testes, but the tumors eventually recur and cause death. A critical question is whether the androgen receptor mediates recurrent tumor growth after androgen deprivation therapy. Here we report that a majority of recurrent prostate cancers express high levels of the androgen receptor and two nuclear receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. Overexpression of these coactivators increases androgen receptor transactivation at physiological concentrations of adrenal androgen. Furthermore, we provide a molecular basis for this activation and suggest a general mechanism for recurrent prostate cancer growth.

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.

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.

Protein kinase Cepsilon interacts with Bax and promotes survival of human prostate cancer cells.

Prostatic glandular epithelial cells express protein kinase Cepsilon (PKCepsilon ), an oncoprotein that coordinately disrupts the reactivation of the tumor suppressor Rb, derepressess transcriptional elongation of the c-myc oncogene, and propagates survival signals in LNCaP cells. Since the activation of such a program may contribute to the progression of human prostate cancer, a proteomic analysis was performed to gain a more global perspective on the signaling network that PKCepsilon might be capable of engaging in prostate cancer cells. Using CWR22 xenografts, we identified at least 18 different structural, signaling, and stress-related proteins that associated with PKCepsilon, including an interaction with the proapoptotic protein Bax that was novel to recurrent CWR22 tumors. An investigation into the biological significance of the PKCepsilon association with Bax provided the first evidence of an inverse relationship between endogenous levels of PKCepsilon and susceptibility of prostate cancer cells to the apoptotic effects of phorbol esters. Western blot and antisense experiments demonstrated that CWR-R1 cells expressed moderate levels of PKCepsilon and relied on this protein to survive in the presence of phorbol esters, while the apoptosis normally induced by phorbol esters in PKCepsilon -deficient LNCaP cells was dependent on the presence of Bax. Forced expression of PKCepsilon in LNCaP cells was sufficient to confer a significant resistance to phorbol esters and this resistance was associated with an inhibition of phorbol ester-induced Bax conformational rearrangements that are important for Bax oligomerization, mitochondrial integration, and cytochrome c release. Considered in their entirety, our data suggest that an association of PKCepsilon with Bax may neutralize apoptotic signals propagated through a mitochondrial death-signaling pathway.