Resolving the bulk ion region of millimeter-wave collective Thomson scattering spectra at ASDEX Upgrade.

Collective Thomson scattering (CTS) measurements provide information about the composition and velocity distribution of confined ion populations in fusion plasmas. The bulk ion part of the CTS spectrum is dominated by scattering off fluctuations driven by the motion of thermalized ion populations. It thus contains information about the ion temperature, rotation velocity, and plasma composition. To resolve the bulk ion region and access this information, we installed a fast acquisition system capable of sampling rates up to 12.5 GS/s in the CTS system at ASDEX Upgrade. CTS spectra with frequency resolution in the range of 1 MHz are then obtained through direct digitization and Fourier analysis of the CTS signal. We here describe the design, calibration, and operation of the fast receiver system and give examples of measured bulk ion CTS spectra showing the effects of changing ion temperature, rotation velocity, and plasma composition.

Commissioning activities and first results from the collective Thomson scattering diagnostic on ASDEX Upgrade (invited).

The collective Thomson scattering (CTS) diagnostic installed on ASDEX Upgrade uses millimeter waves generated by the newly installed 1 MW dual frequency gyrotron as probing radiation at 105 GHz. It measures backscattered radiation with a heterodyne receiver having 50 channels (between 100 and 110 GHz) to resolve the one-dimensional velocity distribution of the confined fast ions. The steerable antennas will allow different scattering geometries to fully explore the anisotropic fast ion distributions at different spatial locations. This paper covers the capabilities and operational limits of the diagnostic. It then describes the commissioning activities carried out to date. These activities include gyrotron studies, transmission line alignment, and beam pattern measurements in the vacuum vessel. Overlap experiments in near perpendicular and near parallel have confirmed the successful alignment of the system. First results in near perpendicular of scattered spectra in a neutral beam injection (NBI) and ion cyclotron resonance heating (ICRH) plasma (minority hydrogen) on ASDEX Upgrade have shown evidence of ICRH heating phase of hydrogen.

Reaching high poloidal beta at Greenwald density with internal transport barrier close to full noninductive current drive.

In the ASDEX Upgrade tokamak, high poloidal beta up to beta(pol) = 3 at the Greenwald density with H-mode confinement has been reached. Because of the high beta, the plasma current is driven almost fully noninductively, consisting of 51% bootstrap and 43% neutral beam driven current. To reach these conditions the discharge is operated at low plasma current ( I(P) = 400 kA) and high neutral beam heating power ( P(NBI) = 10 MW). The discharge combines an edge (H mode) and internal transport barrier at high densities without confinement-limiting MHD activities. The extrapolation to higher plasma currents may offer a promising way for an advanced scenario based fusion reactor.

Experimental evidence for gradient length-driven electron transport in tokamaks.

Energy transport by the electrons in a tokamak is examined in steady-state and power modulation experiments using electron cyclotron heating. The results are consistent with the assumption that temperature profiles are limited by a critical gradient length, leading to "stiff" profiles. The modulation experiments show that the stiffness factor increases with temperature. They strongly suggest that turbulence driven by the electron temperature gradient may be a dominant mechanism of electron transport. Although possibly not universal, these results are valid under various plasma conditions.

Somatic symptoms of generalized anxiety disorder from the DSM-IV: associations with pathological worry and depression symptoms in a nonclinical sample.

The present study investigates specificity of the six somatic symptoms that are associated with generalized anxiety disorder (GAD), according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. A nonclinical sample of 183 students provided severity ratings for (a) restlessness, (b) easily fatigued, (c) difficulty concentrating, (d) irritability, (e) muscle tension, and (f) sleep disturbance. In addition, they responded to questionnaires assessing pathological worry and depression symptoms. Partial correlations and multiple regression analyses indicated that only muscle tension showed a unique relation to pathological worry. In contrast, difficulty concentrating was exclusively related to depression symptoms. Present findings corroborate psychophysiological findings that elevated muscle tension is a specific characteristic of pathological worriers. Moreover, they suggest that the problem of unclear boundaries between GAD and major depression may be reduced if future revisions of the somatic symptom list for GAD emphasize muscle tension while de-emphasizing difficulty concentrating.

Worry, problem elaboration and suppression of imagery: the role of concreteness.

Both lay concept and scientific theory claim that worry may be helpful for defining and analyzing problems. Recent studies, however, indicate that worrisome problem elaborations are less concrete than worry-free problem elaborations. This challenges the problem solving view of worry because abstract problem analyses are unlikely to lead to concrete problem solutions. Instead the findings support the avoidance theory of worry which claims that worry suppresses aversive imagery. Following research findings in the dual-coding framework [Paivio, A. (1971). Imagery and verbal processes. New York: Holt, Rhinehart and Winston; Paivio, A. (1986). Mental representations: a dual coding approach. New York: Oxford University Press.], the present article proposes that reduced concreteness may play a central role in the understanding of worry. First, reduced concreteness can explain how worry reduces imagery. Second, it offers an explanation why worrisome problem analyses are unlikely to arrive at solutions. Third, it provides a key for the understanding of worry maintenance.

Weekly assessment of worry: an adaptation of the Penn State Worry Questionnaire for monitoring changes during treatment.

Development and validation of the Penn State Worry Questionnaire. Behaviour Research and Therapy, 28, 487-495.] for weekly assessment of worry was evaluated in a brief treatment study. Cognitive restructuring techniques were taught to 28 nonclinical high-worriers, 14 of whom served as a control group in a lagged waiting-list design. Results showed that the Penn State Worry Questionnaire-Past Week (PSWQ-PW) was highly reliable and substantially valid in the assessment of both (a) weekly status of worry and (b) treatment-related changes in worry: average Cronbach's alpha was 0.91; average convergent correlation with a past-week adaptation of the Worry Domains Questionnaire [Tallis, F., Eysenck, M. W. and Mathews, A. (1992). A questionnaire for the measurement of nonpathological worry. Personality and Individual Differences, 13, 161-168.] was 0.63 and pre-post improvement on PSWQ-PW showed a 0.71 correlation with the Questionnaire of Changes in Experiencing and Behavior [Zielke, M. and Kopf-Mehnert, C. (1978). Veränderungsfragebogen des Erlebens und Verhaltens. Weinheim, Germany: Beltz Test Gesellschaft.]. It is concluded that the PSWQ-PW is a useful instrument for monitoring pathological worry in experimental and applied settings.

Developmental effects of trichloroacetonitrile administered in corn oil to pregnant Long-Evans rats.

Trichloroacetonitrile (TCAN) is a by-product of the chlorine disinfection of water containing natural organic material. When administered by gavage to pregnant Long-Evans rats in a medium-chain triglyceride vehicle, tricaprylin oil (Tricap), at a volume of 10 ml/kg, TCAN induced fetal cardiovascular anomalies at doses as low as 1 mg/kg/d (Smith et al., 1988). A slight but possibly biologically significant increase over the water control group in adverse pregnancy outcomes (resorptions, reduced fetal weight, and anomalies) was observed in the Tricap control group. This led us to reexamine the development effects of TCAN in a second vehicle, corn oil (CO). Five groups of approximately 20 pregnant female rats received TCAN in CO at 15, 35, 55, and 75 mg/kg/d, and in Tricap at 15 mg/kg/d (10 ml/kg dosing volume). Corn oil, Tricap, and water served as vehicle controls. Animals were treated by oral intubation on gestation d 6-18 (vaginal plug = d 0). Five out of 20 dams (75 mg/kg) died during treatment. Adjusted maternal weight gain was lower in females receiving 35 mg/kg TCAN or greater. The mean percent of nonlive implants per litter was elevated at 55 and 75 mg/kg TCAN (CO). The TCAN dose-response curve for fetal (but not maternal) effects was shifted to the right when CO was compared to Tricap. Fetal weight was reduced at 15 mg/kg TCAN (Tricap) and at > or = 55 mg/kg TCAN (CO). When TCAN was administered in CO, the mean frequency of soft-tissue malformations decreased with significantly fewer septal and great vessel cardiovascular defects observed. We hypothesize that the volatile haloacetonitrile, TCAN, may interact with the Tricap vehicle in such a way that effects on the developing cardiovascular system are potentiated. The lowest observed adverse effect level for TCAN (CO) was determined to be 35 kg/kg.

Activation of two mutant androgen receptors from human prostatic carcinoma by adrenal androgens and metabolic derivatives of testosterone.

The androgen receptor (AR) plays a central regulatory role in prostatic carcinoma and is a target of androgen ablation therapy. Recent detection of mutant receptors in tumor specimens suggest a contribution of AR alterations to progression towards androgen independence. In a specimen derived from metastatic prostate cancer we have reported a point mutation in the AR gene that leads to a single amino acid exchange in the ligand binding domain of the receptor. Another amino acid exchange resulting from a point mutation was also identified 15 amino acids away from our mutation. This mutation was detected in the AR gene isolated from an organ-confined prostatic tumor. Here we report the functional characterization of the two mutant receptors in the presence of adrenal androgens and testosterone metabolites. These studies were performed by cotransfecting androgen-responsive reporter genes and either the wild-type or mutant AR expression vectors into receptor negative DU-145 and CV-1 cells. The indicator genes used consisted of the promoter of the androgen-inducible prostate-specific antigen gene or the C' Delta9 enhancer fragment from the promoter of the mouse sex-limited protein driving the expression of the bacterial chloramphenicol acetyl transferase gene. Cotransfection-transactivation assays revealed that the adrenal androgen androstenedione and two products of testosterone metabolism, androsterone and androstandiol, induced reporter gene activity more efficiently in the presence of the mutant receptors than in the presence of the wild-type receptor. No difference between wild-type and mutant receptors was observed in the presence of the metabolite androstandione. The interaction of receptor-hormone complexes with target DNA was studied in vitro by electrophoretic mobility shift assays (EMSA). Dihydrotestosterone and the synthetic androgen mibolerone induced a faster migrating complex with all receptors, whereas the androgen metabolite androstandione induced this complex only with the two mutant receptors. Androsterone and androstandiol were inactive in the EMSA. These aberrant properties of the mutant receptors in the presence of adrenal androgens and products of androgen metabolism may be of importance in the course of the prostate cancer, especially during androgen ablation therapy.

Mutant androgen receptors in prostatic tumors distinguish between amino-acid-sequence requirements for transactivation and ligand binding.

Mutant androgen receptors are thought to contribute to hormone resistance in prostate carcinoma. The part they play in this process, however, is ill-defined. Here we report on transactivation by 2 mutant androgen receptors from prostatic tumors with single amino-acid exchanges in their hormone-binding domains. These exchanges enhance the transactivation property of the receptors, particularly to androsterone and androstanediol, 2 metabolized derivatives of testosterone present in the prostate. Additionally, they enhance the transactivation potential of the mutant receptors to hydroxyflutamide, an anti-androgen frequently used in hormone ablation therapy. The increased transactivation by the mutant receptors did not result from altered affinity of the receptors to the inducing ligands nor from measurable changes in conformation of the liganded receptors. Thus the single amino-acid exchanges identify differences in amino-acid-sequence requirements for transactivation and ligand binding in the hormone-binding domain of the androgen receptor. These results provide new insights into ligand-dependent transactivation, and form a framework for the search for effective antagonists to be used in prostate-cancer therapy.

Toxicity of 1,1,1-trichloro-2-propanone in Sprague-Dawley rats.

1,1,1-Trichloro-2-propanone (1,1,1-TCP) has been identified as a chlorination by-product in finished drinking water supplies. Since little was known of its oral toxicity, exposure studies were conducted with male and female Sprague-Dawley rats (10 males and 10 females/group) exposed by corn oil gavage at 0, 16, 48, 161, or 483 mg/kg for 10 d or 0, 30, 90, or 270 mg/kg for 90 d. Evaluations included mortality, clinical signs, body weight, food consumption, ophthalmology, hematology, clinical chemistry, urinalysis, organ weights, gross pathology, and histopathology. In the 10-d study, severe toxicity was observed at the highest dose level, since most treated animals (8/10 males and 7/10 females) died. Toxicity was also noted at 161 and 48 mg/kg. At 161 mg/kg, 2 males died and an increase in liver weights in both sexes was observed. Acanthosis and hyperkeratosis of the forestomach was present in males and females at 48 mg/kg and above. In the 90-d study, toxicity was significant at 270 mg/kg, with acanthosis and hyperkeratosis of the forestomach evident in most animals and ataxia in about one-half of them. Retinal degeneration, increased serum potassium, and increased blood urea nitrogen were present in females and increased blood calcium in males at that same dose level. Acanthosis and hyperkeratosis were observed in both sexes, and retinal degeneration was prominent in 2 females at 90 mg/kg. It was concluded that 16 mg/kg was the NOAEL (no observed adverse effect level) for the 10-d study while 30 mg/kg was the NOAEL for the 90-d exposure of Sprague-Dawley rats to 1,1,1,-trichloro-2-propanone.

Perinatal toxicity associated with nickel chloride exposure.

Several reports have suggested that soluble nickel salts may affect development. In this study female Long-Evans rats drank nickel chloride solutions (0, 10, 50, or 250 ppm Ni) for 11 weeks prior to mating and then during two successive gestation (G1, G2) and lactation (L1, L2) periods. Pups were observed until weaning; breeder males were unexposed. Dams drinking 250 ppm consumed less liquid and more food per kilogram body weight than did controls (liquid: prebreeding, G1, and G2; food: prebreeding, G2 and L2). Maternal weight gain was reduced during G1 in the high- and middle-dose groups; indices of reproductive performance were comparable across groups. Pup birth weight was unaltered by treatment and weight gain was reduced only in male pups exposed to 50 ppm Ni during L1. The frequency of perinatal death is the most significant toxicologic finding of the study. The proportion of dead pups per litter was significantly elevated at the high dose in L1 and at 10 and 250 ppm in L2 (50 ppm, P = 0.076), with a dose-related response in both experimental segments. The number of dead pups per litter was significantly increased at each dose in L2. Prolactin levels in pups were unchanged by treatment and were reduced in dams at the high dose. We conclude that 10 ppm Ni represents the lowest observed adverse effect level (LOAEL) in this study.

Subchronic toxicity study of 1,3-dichloropropanone in Sprague-Dawley rats.

1,3-Dichloropropanone (1,3-DCP) has been identified as a by-product of the chlorination of water and thus a potential contaminant in drinking water. Since little was known of its oral toxicity, subchronic exposure studies were conducted with male and female Sprague-Dawley rats exposed to 1,3-DCP in drinking water at 0, 5, 65, or 125 ppm for 90 days. Evaluations included mortality, clinical signs, body weight, food consumption, hematology, clinical chemistry, organ weights, gross pathology, and histopathology. No significant organ toxicity was detected although an aversion to drinking 1,3-DCP treated water was observed at 65 and 125 ppm. The only consistent change was a decrease in BUN at 125 ppm in both sexes. Based on a decrease in BUN levels and decreased water consumption, 5 ppm (0.5 mg/kg/day) was considered the NOAEL.