First measurements of an imaging heavy ion beam probe at the ASDEX Upgrade tokamak.

The imaging heavy ion beam probe (i-HIBP) diagnostic has been successfully commissioned at ASDEX Upgrade. The i-HIBP injects a primary neutral beam into the plasma, where it is ionized, leading to a fan of secondary (charged) beams. These are deflected by the magnetic field of the tokamak and collected by a scintillator detector, generating a strike-line light pattern that encodes information on the density, electrostatic potential, and magnetic field of the plasma edge. The first measurements have been made, demonstrating the proof-of-principle of this diagnostic technique. A primary beam of 85/87Rb has been used with energies ranging between 60 and 72 keV and extracted currents up to 1.5 mA. The first signals have been obtained in experiments covering a wide range of parameter spaces, with plasma currents (Ip) between 0.2 and 0.8 MA and on-axis toroidal magnetic field (Bt) between 1.9 and 2.7 T. Low densities appear to be critical for the performance of the diagnostic, as signals are typically observed only when the line integrated density is below 2.0-3.0 × 1019 m-2 in the central interferometer chord, depending on the plasma shape. The strike line moves as expected when Ip is ramped, indicating that current measurements are possible. Additionally, clear dynamics in the intensity of the strike line are often observed, which might be linked to changes in the edge profile structure. However, the signal-to-background ratio of the signals is hampered by stray light, and the image guide degradation is due to neutron irradiation. Finally, simulations have been carried out to investigate the sensitivity of the expected signals to plasma density and temperature. The results are in qualitative agreement with the experimental observations, suggesting that the diagnostic is almost insensitive to fluctuations in the temperature profile, while the signal level is highly determined by the density profile due to the beam attenuation.

Insulin-degrading enzyme higher in subjects with metabolic syndrome.

Metabolic syndrome (MS) is comprised of a cluster of abnormalities in glucose, lipid, and vascular homeostasis, which is most commonly linked to abdominal obesity. MS heralds increased risk for development of diabetes and is linked to impairment in insulin signaling. Insulin-degrading enzyme (IDE) is one of the mechanisms through which insulin blood levels are maintained. It has been previously suggested that controlling IDE levels could provide yet another potential therapeutic approach in diabetes. Here we aim to investigate whether changes in serum IDE levels correlate with the severity of MS. Using a highly sensitive ELISA assay of active IDE in human serum, we found a strong correlation between circulating IDE levels and circulating levels of triglycerides, insulin, and c-peptide and an inverse correlation with HDL cholesterol (HDLc). Serum IDE levels were higher in MS subjects than in control subjects. Hence, circulating IDE may serve as a tool to identify subjects with abnormal insulin metabolism, possibly those with MS that are at risk to develop diabetes.

JET diagnostic enhancements testing and commissioning in preparation for DT scientific campaigns.

In order to optimize the scientific exploitation of JET (Joint European Torus) during the upcoming deuterium-tritium experiments, a set of diagnostic systems is being enhanced. These upgrades focus mainly on the experimental and operational conditions expected during tritium campaigns. It should be stressed that measurements relevant for burning plasmas are specifically targeted. Previously non-available capabilities, such as a current measurement system fully covering all poloidal field circuits, are described in detail. Instrument descriptions, performance prediction, testing, and initial commissioning results of these systems are presented.

Advanced neutral alkali beam diagnostics for applications in fusion research (invited).

Diagnosing the density profile at the edge of high temperature fusion plasmas by an accelerated lithium beam is a known technique since decades. By knowledge of the relevant atomic physics rate coefficients, the plasma electron density profile can be calculated from the relatively calibrated light profile along the beam. Several additional possibilities have already been demonstrated: Charge Exchange Resonance Spectroscopy (CXRS) for ion temperature/flow and Zeeman polarimetry for edge plasma current; therefore the Li-beam diagnostic offers a wealth of information at the plasma edge. The weaknesses of the method are the relatively faint light signal, background light, and technical difficulties of the beam injector which usually seriously limit the applicability. In this talk, we present systematic developments in alkali-beam diagnostics (Li, Na) for the injector and the observation system and detectors which resulted in strongly increased capabilities. Advanced systems have been built, and microsecond scale density profile, turbulence, and zonal flow measurement have been demonstrated. A novel edge current measurement technique has also been designed, and components have been tested with potential microsecond-scale time resolution. Additional possibilities of these advanced systems for spectral measurements (CXRS and various Zeeman schemes) are also discussed.

Ultrafast two-dimensional lithium beam emission spectroscopy diagnostic on the EAST tokamak.

A diagnostic instrument is described for the Experimental Advanced Superconducting Tokamak (EAST) for the measurement of the edge plasma electron density profile and plasma turbulence properties. An accelerated neutral lithium beam is injected into the tokamak and the Doppler shifted 670.8 nm light emission of the Li2p-2s transition is detected. A novel compact setup is used, where the beam injection and observation take place from the same equatorial diagnostic port and radial-poloidal resolution is achieved with microsecond time resolution. The observation direction is optimized in order to achieve a sufficient Doppler shift of the beam light to be able to separate from the strong edge lithium line emission on this lithium coated device. A 250 kHz beam chopping technique is also demonstrated for the removal of background light. First results show the capability of measuring turbulence and its poloidal flow velocity in the scrape-off layer and edge region and the resolution of details of transient phenomena like edge localized modes with few microsecond time resolution.

Sub-millisecond electron density profile measurement at the JET tokamak with the fast lithium beam emission spectroscopy system.

Diagnostic alkali atom (e.g., lithium) beams are routinely used to diagnose magnetically confined plasmas, namely, to measure the plasma electron density profile in the edge and the scrape off layer region. A light splitting optics system was installed into the observation system of the lithium beam emission spectroscopy diagnostic at the Joint European Torus (JET) tokamak, which allows simultaneous measurement of the beam light emission with a spectrometer and a fast avalanche photodiode (APD) camera. The spectrometer measurement allows density profile reconstruction with ∼10 ms time resolution, absolute position calculation from the Doppler shift, spectral background subtraction as well as relative intensity calibration of the channels for each discharge. The APD system is capable of measuring light intensities on the microsecond time scale. However ∼100 µs integration is needed to have an acceptable signal to noise ratio due to moderate light levels. Fast modulation of the beam up to 30 kHz is implemented which allows background subtraction on the 100 µs time scale. The measurement covers the 0.9 < ρpol < 1.1 range with 6-10 mm optical resolution at the measurement location which translates to 3-5 mm radial resolution at the midplane due to flux expansion. An automated routine has been developed which performs the background subtraction, the relative calibration, and the comprehensive error calculation, runs a Bayesian density reconstruction code, and loads results to the JET database. The paper demonstrates the capability of the APD system by analyzing fast phenomena like pellet injection and edge localized modes.

Plasma radiation dynamics with the upgraded Absolute Extreme Ultraviolet tomographical system in the Tokamak à Configuration Variable.

We introduce an upgraded version of a tomographical system which is built up from Absolute Extreme Ultraviolet-type (AXUV) detectors and has been installed on the Tokamak à Configuration Variable (TCV). The system is suitable for the investigation of fast radiative processes usually observed in magnetically confined high-temperature plasmas. The upgrade consists in the detector protection by movable shutters, some modifications to correct original design errors and the improvement in the data evaluation techniques. The short-term sensitivity degradation of the detectors, which is caused by the plasma radiation itself, has been monitored and found to be severe. The results provided by the system are consistent with the measurements obtained with the usual plasma radiation diagnostics installed on TCV. Additionally, the coupling between core plasma radiation and plasma-wall interaction is revealed. This was impossible with other available diagnostics on TCV.

Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor.

Nissen fundoplication and gastrointestinal-related complications: a guide for the primary care physician.

Gastroesophageal reflux disease is a common condition affecting many individuals in the Western world. Most patients are managed successfully with acid suppression, while others may require more invasive interventions. The majority of patients undergoing antireflux surgery will have favorable outcomes. A small percentage, however, will be considered surgical failures and will either present with new or recurrent symptoms, or develop postoperative complications. These include, but are not limited to, symptoms such as dysphagia, gas-bloat syndrome, and bowel dysfunctions that may significantly impair the patient's health and quality of life. As the number of antireflux procedures for this condition continue to increase, the number of complications is also likely to become more prevalent. The primary care physician will be challenged to recognize them and initiate appropriate management. In this review, we address the more common gastrointestinal complications of laparoscopic Nissen fundoplication and offer general guidelines in their diagnosis and management.

Obesity and complicated diverticular disease: is there an association?

OBJECTIVE: Obesity is becoming a growing health concern in the general population. Multiple studies have linked diverticular disease to obesity. Furthermore, recent research has shown fat to be a critical element in the regulation of immunity and the inflammatory response. In this study, we sought to determine if body mass index (BMI) is associated with a higher incidence of complicated diverticulitis. METHODS: A retrospective review of patients hospitalized with complicated diverticulitis between 1997 and 2006 was conducted. Medical, surgical and CT (Computed Tomography) guided interventions were evaluated in reference to age, gender, BMI and length of hospital stay (LOS). RESULTS: Charts of 104 controls and 614 patients hospitalized with complicated diverticulitis were reviewed based on specified inclusion and exclusion criteria. There was no significant difference between groups by either gender (P = 0.066) or BMI (P = 0.648). There was a significant difference in age and LOS between three of the analyzed groups. No correlation was noted between BMI and LOS in any of the groups. DISCUSSION: There has been increasing interest in obesity and its ramifications in all areas of medicine, including diverticular disease. Numerous studies have shown a strong correlation between acute diverticulitis and obesity, particularly in the young population. This study was undertaken to identify a possible link between complicated diverticulitis and obesity. Anecdotal reports and a few studies have found a parallel association. However, in this retrospective study, no correlation was found between BMI and the incidence of complicated diverticulitis.

Regulation of sterol biosynthesis in sunflower by 24(R,S),25-epiminolanosterol, a novel C-24 methyl transferase inhibitor.

Whereas sitosterol and 24(28)-methylene cycloartanol were competitive inhibitors (with Ki = 26 microM and 14 microM, respectively), 24(R,S)-25-epiminolanosterol was found to be a potent non-competitive inhibitor (Ki = 3.0 nM) of the S-adenosyl-L-methionine-C-24 methyl transferase from sunflower embryos. Because the ground state analog, 24(R,S)-oxidolanosterol, failed to inhibit the catalysis and 25-azalanosterol inhibited the catalysis with a Ki of 30 nM we conclude that the aziridine functions in a manner similar to the azasteriod (Rahier, A., et al., J. Biol. Chem. (1984) 259, 15215) as a transition state analog mimicking the carbonium intermediate found in the normal transmethylation reaction. Additionally, we observed that the aziridine inhibited cycloartenol metabolism (the preferred substrate for transmethylation) in cultured sunflower cells and cell growth.

The metabolism of sunflower phytoalexins ayapin and scopoletin: plant-fungus interactions.

The coumarin phytoalexins ayapin and scopoletin accumulate in longitudinal stem sections of sunflower (Helianthus annuus L., Compositae) following inoculation with fungi both pathogenic (Alternaria helianthi) and nonpathogenic (Helminthosporium carbonum) to this plant. Both compounds were induced more rapidly, and they attained higher levels in tissue inoculated with the heterologous pathogen H. carbonum as compared with the sunflower pathogen A. helianthi. Similarly, scopoletin and ayapin accumulated to comparatively low concentrations following inoculation with a second sunflower pathogen, Phoma macdonaldii. Scopoletin was biosynthesized de novo following inoculation, although levels of its glucoside scopolin exceeded those of the aglucone in both infected and control tissues. Both scopoletin and scopolin were routinely detected in trace amounts in uninoculated tissue. In contrast, ayapin was not detected as a component of uninfected plants. When [(14)C]scopoletin was supplied to induced sunflower stem sections about 36% of the recovered radioactivity was in the form of ayapin. In vitro studies demonstrated that A. helianthi possessed the ability to rapidly degrade both scopoletin and ayapin, whereas H. carbonum was much less efficient in these traits. The differential degradation of these compounds by phytopathogenic fungi which do not attack sunflower is also discussed.

Timing of Diosgenin Appearance in Suspension Cultures of Dioscorea deltoidea.

Cycloheximide and compactin were added to cell suspension cultures of DIOSCOREA DELTOIDEA. Cycloheximide inhibited growth and diosgenin biosynthesis completely at 40 mg/l when added during the growth phase. Compactin partially inhibited growth and diosgenin production at 100 microg/l when added during the growth phase. [1- (14)C]-Acetate incorporation into diosgenin was about 20-fold higher when added during the early stages of growth as compared to addition in the stationary phase. Incorporation of [1- (14)C]-acetate into diosgenin was inhibited by compactin only during the early stages of growth. These results indicate the formation of an accumulating intermediary metabolite during the early stages of growth which is transformed into diosgenin when D. DELTOIDEA cells are in the stationary phase.

Isolation and characterization of an intermediate steroid metabolite in diosgenin biosynthesis in suspension cultures of Dioscorea deltoidea cells.

The aglycon form of the steroidal sapogenin furost -5-ene-3 beta, 22,26-triol, 3 beta- chacotrioside 26 beta-D-glucopyranoside was isolated from cell suspension cultures of Dioscorea deltoidea and its molecular structure was determined by mass spectrometry and 1H and 13C n.m.r. spectroscopy. From kinetic studies and incorporation experiments with [1-14C]acetate it was concluded that the steroidal compound (in the glycoside form) is an intermediate in vivo in diosgenin biosynthesis. It accumulated in growing cells of D. deltoidea and was metabolized to diosgenin (in the glycoside form, i.e. dioscin ) in non-dividing cells.

Factors affecting growth and product formation in plant cells grown in continuous culture.

In the present work we examined the potential benefits of the continuous culture (chemostat) technique at improving biomass yields of Mentha and Dioscorea cells and product formation (diosgenin) by Dioscorea cells. In contrast to Mentha cells, Dioscorea cells were sensitive to mechanical agitation in the exponential growth phase and could only be grown in a bubble column type fermentor. Maximal biomass yield of 0.5 and 0.4 g cell dry weight g(-1)sucrose were obtained for Mentha and Dioscorea cells, respectively. When the phosphate concentration during the growth phase of Dioscorea was increased, a maximal concentration of 7.8% diosgenin (of dry weight) was obtained. Productivity of diosgenin was 12 mg 1(-1) day(-1) in a two-stage continuous process as compared to 7.3 mg 1(-1) day(-1) in a batch culture.

Growth and diosgenin production by Dioscorea deltoidea cells in batch and continuous cultures.

This paper reports the kinetics of growth and diosgenin production in batch cultures, and the application of the continuous culture (chemostat) technique to Dioscorea deltoidea cells. In batch cultures, biomass production was dependent on the concentration (up to 60 g/liter) of the carbon source (sucrose); the cellular yield value obtained was 0.4 g cell dry wt/g sucrose utilized. Diosgenin was synthesized only after growth had ceased; its synthesis proceeded for about 18 days and a concentration of 1.8% (of cell dry wt.) was obtained. D. deltoidea cells were grown at steady state conditions, at a constant growth rate in a chemostat. Only small amounts of diosgenin were produced by growing cells in the chemostat.

The effect of medium constituents on growth and diosgenin production by Dioscorea deltoidea cells grown in batch cultures.

The effect of nitrogen and carbon sources on growth and diosgenin production was studied with Dioscorea deltoidea cells which were grown under defined conditions in a chemostat, and transferred to batch cultures. Both ammonium and nitrate nitrogen were required for growth and steroid production; diosgenin production was maximal at higher amounts of nitrogen. The nature and concentration of the carbon source (sugar) had marked effects on diosgenin production. A maximal amount of diosgenin (3.8% of dry wt.) was produced on sucrose (15 g/liter) after 21 days of growth in a batch culture.