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Advanced tokamak (AT) research in DIII-D seeks to provide a scientific basis for steady-state high performance operation in future devices. These regimes require high toroidal beta to maximize fusion output and high poloidal beta to maximize the self-driven bootstrap current. Achieving these conditions requires integrated, simultaneous control of the current and pressure profiles and active magnetohydrodynamic stability control. The building blocks for AT operation are in hand. Resistive wall mode stabilization by plasma rotation and active feedback with non-axisymmetric coils allows routine operation above the no-wall beta limit. Neoclassical tearing modes are stabilized by active feedback control of localized electron cyclotron current drive (ECCD). Plasma shaping and profile control provide further improvements. Under these conditions, bootstrap supplies most of the current. Steady-state operation requires replacing the remaining inductively driven current, mostly located near the half radius, with non-inductive external sources. In DIII-D this current is provided by ECCD, and nearly stationary AT discharges have been sustained with little remaining inductive current. Fast wave current drive is being developed to control the central magnetic shear. Density control, with divertor cryopumps, of AT discharges with ELMing H-mode edges facilitates high current drive efficiency at reactor relevant collisionalities. An advanced plasma control system allows integrated control of these elements. Close coupling between modelling and experiment is key to understanding the separate elements, their complex nonlinear interactions, and their integration into self-consistent high performance scenarios. This approach has resulted in fully non-inductively driven plasmas with ?N ? 3.5 and ?T ? 3.6% sustained for up to 1?s, which is approximately equal to one current relaxation time. Progress in this area, and its implications for next-step devices, will be illustrated by results of these and other recent experiment and simulation efforts.

Advanced Tokamak (AT) research in DIII-D [K. H. Burrell for the DIII-D Team, in Proceedings of the 19th Fusion Energy Conference, Lyon, France, 2002 (International Atomic Energy Agency, Vienna, 2002) published on CD-ROM] seeks to provide a scientific basis for steady-state high performance operation in future devices. These regimes require high toroidal beta to maximize fusion output and poloidal beta to maximize the self-driven bootstrap current. Achieving these conditions requires integrated, simultaneous control of the current and pressure profiles, and active magnetohydrodynamic stability control. The building blocks for AT operation are in hand. Resistive wall mode stabilization via plasma rotation and active feedback with nonaxisymmetric coils allows routine operation above the no-wall beta limit. Neoclassical tearing modes are stabilized by active feedback control of localized electron cyclotron current drive (ECCD). Plasma shaping and profile control provide further improvements. Under these condi...

High current, stable tokamak plasmas with edge safety factor below or around 2 are attractive for magnetic fusion due to favourable high fusion gain and higher confinement. But they have long been considered inaccessible in modern devices owing to the unforgiving MHD instabilities. Even in devices with a resistive wall, the onset of an n=1 resistive wall mode (RWM) leads to a disruptive limit at edge safety factor qedge=2 (for limiter plasmas) and q95 2 (diverted plasmas). Recently long leaps have been made by DIII-D and RFX-mod through active control of MHD stability by the application of three-dimensional magnetic field [1,2,3]. This paper describes how for the first time two very different tokamaks, a MA-class shaped device like DIII-D and a high aspect ratio circular experiment like RFX-mod (operated as a tokamak), have robustly overcome the edge safety factor = 2 limit by active control of plasma stability and demonstrated that operation below 2 is possible for hundreds of resistive wall times. In addition these experiments have revealed a new tool to control sawtooth frequency and amplitude, a result that has the potential of extending the tokamak operating space even further by avoiding the deleterious effects of long-period sawteeth. Comparison with theory and numerical modelling of stability and of the effect of externally applied 3D fields in low edge q plasmas is presented.

High current, stable tokamak plasmas with edge safety factor below or around 2 are attractive for magnetic fusion due to favourable high fusion gain and higher confinement. But they have long been considered inaccessible in modern devices owing to the unforgiving MHD instabilities. Even in tokamaks with a resistive wall, the onset of an n 1 resistive wall mode leads to a disruptive limit at edge safety factor q edge 2 (for limiter plasmas) and q 95 2 (diverted plasmas). This paper reports how for the first time two very different tokamaks, a large MA-class shaped device like DIII-D and a high aspect ratio circular experiment like RFX-mod, have robustly overcome the edge safety factor 2 limit by active control of plasma stability and demonstrate that operation below 2 is possible for hundreds of resistive wall times. In addition these experiments reveal a new tool to control sawtooth frequency and amplitude, a result that has the potential of extending the tokamak operating space even further by avoiding deleterious giant sawteeth. The application of 3D fields with a strong n 1 component that couples to the m 1 ;n 1 internal kink is found to significantly reduce the sawtooth amplitude and increase their frequency, demonstrating the benefits of this helical state. Experimental results have been compared with theory and numerical models. The experimental stability limit has been identified in DIII-D limiter plasmas as q edge 2 : 08 0 : 011 , slightly higher than the external kink mode limit q edge 2 : 0 predicted by ideal MHD analysis (DCON). In both devices the approach to the stability limit is characterized by the onset of an n 1 ;m 2 mode and growth rate of the order of wall , consistent with ideal MHD predictions. RFX-mod shows that at q edge + 2 : 0 the growth rate of the uncontrolled modes decreases as q edge is lowered towards 1.5, i.e., indicating stability improvement as q edge 1 : 5 is approached from above. This is consistent with external kink mode stability expected from ideal MHD theory at q edge + 2 : 0 : a peak in the external kink growth rate is expected near, but below q edge 2 : 0 , followed by a decrease in the growth rate. Sawtooth destabilization via applied magnetic perturbation is explained with the nonlinear MHD PIXIE3D code as a purely nonlinear effect, and not simply a modification of the p 1 ; 1 q kink linear stability.

The DIII-D divertor baffle system was designed to facilitate density control in long pulse H-mode discharges by removing a particle flux equal to the neutral beam fueling rate (∼20 Torrl/s) with a ∼1 mTorr neutral pressure under the baffle (p0). Initial measurements of the baffle pressure indicated that p0∼10 mTorr (without pumping or biasing), a value much in excess of that required for long pulse density control. Radial sweeps of the X-point position have been employed to determine the maximum p0, as well as to establish the dependence of this pressure on geometry. An estimate of the particle equilibration time for the baffle system has been made by studying the baffle pressure response to “giant” ELM effects. “Steady state” experiments in which the X-point position was fixed for ∼2.5 s have also been carried out and steady baffle pressures were observed. The scaling of baffle pressure with plasma parameters has been found to be similar under transient and “steady state” conditions. Detailed modeling of these experiments with the B2, DEGAS, and WDIFFUSE (wall model) codes has been performed.

Particle control of both hydrogen and impurity atoms is important in obtaining reproducible discharges with a low fraction of radiated power in the DIII–D tokamak. The main DIII–D plasma facing components are graphite tiles (40% of the total area and covering regions exposed to the highest heat fluxes) and Inconel. Hydrogenic species desorbed from graphite during a tokamak discharge can be a major fueling source, especially in unconditioned graphite where these species can saturate the surface regions. In this case the recycling coefficient can exceed unity, leading to an uncontrolled density rise. In addition to removing volatile hydrocarbons and oxygen, DIII–D vessel conditioning efforts have been directed at the reduction of particle fueling from the graphite tiles. Conditioning techniques include: baking to ≤400 °C, low power pulsed discharge cleaning, and glow discharges in deuterium, helium, neon, or argon. Helium glow wall conditioning, is now routinely performed before every tokamak discharge. The...

A regime of very high confinement (VH mode) has recently been observed in DIII‐D with global energy confinement times up to a factor of 3.5 above the ITER89‐P L‐mode scaling [Nucl. Fusion 30, 1999 (1990)] and 1.5 to 2 times greater than the DIII‐D/JET edge‐localized‐mode‐free H‐mode scaling relation [Nucl. Fusion 31, 73 (1991)]. These discharges were obtained after boronization in DIII‐D and are characterized by low radiated power and Zeff, increasing confinement time during the VH phase of the discharge and low Ohmic target density. The low radiated power and Zeff are a consequence of the boronization. During the VH phase these discharges exhibit an inward shift in the region of highest electric field shear and a large calculated edge bootstrap current. The outer region (ρ≳0.85) is calculated to be in the second stable regime to ideal ballooning modes.

Small (o.d. = 1.8 mm, t = 0.37 mm) polystyrene shells filled with either pressurized argon gas or boron powder have been fired into DIII‐D plasmas for disruption mitigation experiments. The pellet shells were observed to burn up at ρ≈0.5, roughly consistent with ablation rate calculations. Pellet slowing from 350 m/s down to 100 m/s was observed, which is not well‐understood at present. Negligible plasma current contraction or MHD onset were seen as a result of the shell burn‐up in the plasma edge, consistent with calculations. The pellet payloads were observed to ionize rapidly in the pellet vicinity (

Glow discharge conditioning of tokamaks with graphite plasma‐facing surfaces has been used to reduce impurities and obtain density control of the plasma discharge. However, a major operational disadvantage of glow conditioning is the high pressure required to initiate the glow discharge, e.g., ≊70 mTorr for helium in DIII‐D, which requires isolating auxiliary components that can not tolerate the high pressure. An electron‐gun‐assisted glow discharge can lower breakdown pressure, possibly eliminating the necessity of isolating these auxiliary systems during glow discharge conditioning and allowing glow discharge operation at lower pressures. An electron‐assisted glow discharge experiment has been carried out in a small vacuum vessel to evaluate whether such a system can be employed in the DIII‐D tokamak. With an electron gun to produce an initial source of electrons, the pressure at which a helium glow discharge can be initiated has been decreased by two orders of magnitude. The glow was produced in a 0.40...

Advanced Tokamak research in DIII-D seeks to develop a scientific basis for steady-state high-performance tokamak operation. Fully noninductive (fNI≈ 100%) in-principle steady-state discharges have been maintained for several confinement times. These plasmas have weak negative central shear with qmin≈ 1.5-2, βN≈ 3.5, and large, well-aligned bootstrap current. The loop voltage is near zero across the entire profile. The remaining current is provided by neutral beam current drive (NBCD) and electron cyclotron current drive (ECCD). Similar plasmas are stationary with fNI≈ 90-95% and duration up to 2 s, limited only by hardware. In other experiments, βN≈ 4 is maintained for 2 s with internal transport barriers, exceeding previously achieved performance under similar conditions. This is allowed by broadened profiles and active magnetohydrodynamic instability control. Modifications now underway on DIII-D are expected to allow extension of these results to higher performance and longer duration. A new pumped divertor will allow density control in high triangularity double-null divertor configurations, facilitating access to similar in-principle steady-state regimes with βN> 4. Additional current drive capabilities, both off-axis ECCD and on-axis fast wave current drive (FWCD), will increase the magnitude, duration, and flexibility of externally driven current. © 2006 Elsevier B.V. All rights reserved.

Extensive studies to date of edge localized modes (ELMs) have sought their origin inside the separatrix, i.e., MHD instability from steep gradients in the plasma edge, and examined their consequences outside the separatrix, i.e., transport of heat and particles in the scrape-off-layer (SOL) and divertors. Recent measurement by a high-speed scrape-off-layer current (SOLC) diagnostic may indicate that the ELM trigger process lies, in part, in the SOL. Thermoelectrically driven SOLC precedes, or co-evolves with, other parameters of the ELM process, and thus can potentially play a causal role: error field generated by non-axisymmetric SOLC, flowing in the immediate vicinity (approximately 1 cm) of the plasma edge, may contribute toward destabilizing MHD modes. The SOLC, observed concurrently with MHD activity, including ELMs, has been reported elsewhere.

The frequency and amplitude of GnRH and LH pulses are variable and controlled by both external environmental and internal physiological factors. However, the specific neurochemical-neuroanatomical pathways that control the basal pulsatile and surge patterns, and mediate responses to environmental and physiological factors are poorly defined. The gamma-aminobutyric acid (GABA) secretory system is one of several that modulate GnRH and LH. GABA release in the preoptic area (POA) preceding the onset of oestrogen-induced LH surges changes in a pattern that is inverse to LH release. Application of GABA agonists or antagonists to either the POA or mediobasal hypothalamus disrupts LH secretion. Observations that application of GABA(B) agonists to either the POA or mediobasal hypothalamus rapidly reverses the negative feedback effect of oestrogen or testosterone on LH lead the authors to suggest that GABA(B) receptors have an important role in regulating LH secretion in sheep.

Impurity seeding in both the Joint European Torus (JET) and DIII-D tokamaks has produced L-mode discharges with confinement enhancements comparable to H-mode and a near doubling of the core ion temperature when compared,to similar unseeded discharges. Although Z(eff) increases with the neon injection, the total neutron rate is as high, or higher, than reference discharges and the calculated thermal neutron rate increases dramatically in both devices. Modelling with the gyrokinetic simulation code shows a reduction in low k turbulence growth rates with neon injection decreasing to less than the E x B shearing rate, consistent with stabilization of ion temperature gradient modes in both JET and DIII-D. Reductions in ion thermal diffusivity are also observed with impurity seeding. Neoclassical m/n = 3/2 tearing modes limit the duration of best performance in DIII-D with neon injection, while n = 1 and n = 2 magnetohydrodynamic modes limit the performance in JET.

Infusion of baclofen, a GABA(B) agonist, into the medial basal hypothalamus (MBH) of castrated rams rapidly increases LH pulse amplitude without altering pulse frequency. The objectives of this study were to determine whether baclofen infusion increased LH in testosterone (T)-treated and intact rams, the increased LH was due to increased GnRH release, and FSH secretion also was increased. In the first experiment we tested the main effects and interaction of baclofen and T on FSH and LH pulse patterns in castrated rams (n = 7). In the second experiment we determined whether baclofen affected GnRH and LH pulses in intact males. Microdialysis guide cannulae were implanted bilaterally into the MBH. After recovery of the animal from surgery, the MBH was perfused using concentric microdialysis probes (2-mm tip) with artificial cerebrospinal fluid (aCSF) for a 3-h control period followed by either aCSF or 1 mM baclofen for 4 h. Blood samples were taken at 10-min intervals. T suppressed mean LH concentrations (10.4 +/- 1.3 vs. 3.3 +/- 1.3 ng/ml) such that LH pulses were undetectable in some T-treated animals during the control period. The change (control period vs. drug infusion period) in mean LH was greater in response to baclofen than in response to aCSF and was not altered by T. The baclofen x T interaction was nonsignificant. Mean FSH was decreased by T, but was not altered by baclofen. In the second experiment hypophyseal portal blood was collected coincident with microdialysis. Infusion of baclofen into the MBH of intact males (n = 7) resulted within 1 h in the onset of frequent and robust GnRH pulses (0.10/h before baclofen vs. 1.57/h after baclofen) that were followed either immediately or gradually by coincident LH pulses. One interpretation is that baclofen acts downstream of the site of action of T. GABA(B) receptors may regulate pulse amplitude in both the presence and absence of T and regulate pulse frequency by modulating the inhibitory effect of T.

In males, including the ram, testosterone, acting via its primary metabolites oestradiol and dihydrotestosterone (DHT), suppresses circulating LH concentrations. This effect is due primarily, although not totally, to decreased frequency of gonadotrophin-releasing hormone (GnRH) pulses. The arcuate-ventromedial region (ARC-VMR) of the mediobasal hypothalamus and possibly the medial preoptic area (mPOA) are sites at which oestradiol acts to suppress GnRH, but the site of DHT action is not known. Given that native GnRH neurones appear to contain few or no oestrogen or androgen receptors, the effects of testosterone metabolites probably are exerted by modulating activity of inhibitory interneurone systems such as beta-endorphin, dopamine, and gamma-aminobutyric acid (GABA). Although beta-endorphin clearly inhibits GnRH secretion, the observation that testosterone treatment during a long-day photoperiod reduced proopiomelanocortin (POMC) mRNA in the arcuate nucleus while coincidentally suppressing GnRH release indicates that beta-endorphin does not mediate the inhibitory effect of testosterone on GnRH. Activation of GABAA receptors in either the mPOA or ARC-VMR suppressed LH, whereas activation of GABAB receptors in the ARC-VMR increased LH pulse amplitude. Therefore, it is suggested that GABA acts in both regions to regulate LH. Whereas testosterone affects GABA metabolism in the rat hypothalamus, its effect in the ram hypothalamus is yet to be determined. Testosterone treatment activated dopaminergic cells in the retrochiasmatic A15 area in the same animals in which it suppressed POMC mRNA in the arcuate nucleus. This dopaminergic system may partially mediate the negative feedback effect of testosterone in the ram analogous to its role in partially mediating the negative effect of oestrogen in the ewe. Future studies must concentrate on determining how these and other putative inhibitory neuronal systems interact and how they in turn are regulated by environmental factors such as photoperiod.

As a first step in determining possible influences of the newly discovered estrogen receptor (ER)-beta on reproduction, we have localized mRNA for ER-beta within the male sheep hypothalamus using in situ hybridization and a rat ER-beta cRNA probe. Highest amounts of hybridization signal were observed in the preoptic area (POA), bed nucleus of the stria terminalis, paraventricular nucleus, and supraoptic nucleus. Relatively moderate amounts of hybridization signal were observed in the retrochiasmatic area (RCH), anterior hypothalamic area, dorsomedial hypothalamus, and lateral hypothalamus. Only a low level of hybridization signal was observed in the ventromedial hypothalamus, suprachiasmatic nucleus, and arcuate nucleus. The presence of ER-beta mRNA in several areas of the male sheep hypothalamus suggests multiple functions for this receptor. The distribution of ER-beta in the ovine hypothalamus was similar to that described for the rat, suggesting a high degree of functional conservation across species. A role for ER-beta in influencing reproduction is suggested by its presence in the POA and RCH, regions of the hypothalamus that control reproduction.

This study tested the hypothesis that photoperiod affects the ability of testosterone to reduce proopiomelanocortin (POMC) mRNA levels in the arcuate nucleus and luteinizing hormone-releasing hormone (LHRH) mRNA levels in both the preoptic area (POA) or medial basal hypothalamus (MBH). Twenty castrated male sheep were assigned to one of four treatment groups (i): short days (SD; n=5) (ii), short days with testosterone (SD+T; n=5) (iii), long days (LD; n=5), or (iii) long days with testosterone (LD+T; n=5). Blood samples were collected twice weekly for the last 3 weeks of photoperiod treatment and assessed for LH to validate the response to photoperiod. After evaluating LH levels, one animal each from the LD+T and SD+T groups was excluded from the analyses. Mean concentrations of LH were lower (P0.01) in the LD+T group than in the other treatment groups, which did not differ (P0.10) from each other. Neither POA nor MBH LHRH mRNA levels were affected (P0.10) by treatment. Conversely, POMC mRNA levels were suppressed (P0.01) in the LD+T males compared with the other treatment groups which did not differ (P0.10) from each other. These observations suggest that photoperiod specific, testosterone-induced alterations in LHRH mRNA levels are not a mechanism whereby testosterone suppresses LHRH release, and that increased beta-endorphin synthesis and release do not mediate testosterone-induced seasonal suppression of LHRH release.

We investigated the effects of microdialyzing alpha-aminobutyric acid (GABA) receptor antagonists into either the medial preoptic area (mPOA) or the arcuate-ventromedial region (ARC-VMR) on LH secretion. Bicuculline methiodide (BMI, GABA(A) receptor antagonist), and either 2-hydroxysaclofen (SAC) or CGP 55845A (CGP, GABA(B) receptor antagonists) were used. In experiment 1, castrated rams received 4-h dialysis into either the mPOA (n = 5) or ARC-VMR (n = 4) of artificial cerebrospinal fluid (aCSF) followed by 4 h of either BMI (aCSF-BMI, 375 microM in mPOA, 1 mM in the ARC-VMR for 2-1/2 h), or aCSF-SAC (5 mM). In experiment 2, castrated rams received dialysis only in the ARC-VMR (n = 5) of aCSF-aCSF, aCSF-BMI (375 microM), or aCSF-CGP (50 microM). In experiment 3, untreated or testosterone (T)-treated castrated rams (n = 6/group) received dialysis only in the ARC-VMR of aCSF-aCSF, aCSF-BMI (375 microM), or aCSF-CGP (500 microM). Jugular blood was collected at 10-min intervals. In experiment 1, BMI suppressed mean plasma LH (p0.05) and increased interpulse interval (IPI, p0.05) at both sites. In experiment 2, BMI significantly reduced mean LH and increased IPI (p0.01). In experiment 3, BMI reduced mean LH in both the presence (p0.05) and absence of T (p0.01) and increased IPI (p0.01) in the absence of T. SAC, CGP, and aCSF did not affect LH in any experiment. These results show that dialysis of BMI, into either the mPOA or the ARC-VMR of either castrated or T-treated castrated rams decreased LH release, whereas dialysis of GABA(B) antagonists at these sites was without detectable effect.

Testosterone (T) inhibits LH secretion partly by acting at unknown sites within the brain to inhibit GnRH secretion. We tested the hypothesis that the preoptic area (POA) and arcuate-ventromedial region (ARC/VMR), areas rich in androgen and estrogen (E) receptors, are neural sites at which T and the T metabolites, dihydrotestosterone (DHT) and estrogen (E), act to suppress LH secretion. Bilateral guide cannulae were surgically implanted into either the POA or ARC/VMR of castrated male sheep. Experiments were conducted under a long day photoperiod to maximize the inhibitory effect of the steroids. In Exp 1, all sheep (n = 6/site) sequentially received bilateral implants of cholesterol (CHOL), T, or E at each site. Jugular blood samples were taken at 10-min intervals for 4 h both immediately before implant insertion and 5 days later. In Exp 2, all sheep (n = 6/site) sequentially received bilateral implants of CHOL, DHT, or E at each site according to a latin square design. Blood samples were taken before and 7 days after implant insertion. In Exp 3, which followed the same design as Exp 2, implants of E, T, or DHT were placed only in the ARC/VMR. In the final experiment, the effects of T and CHOL implants in the ARC/VMR were compared. Neither T, DHT, nor CHOL implants at either site affected LH secretion. In contrast, E treatment in the ARC/VMR suppressed mean plasma LH levels (P0.01), primarily due to an increase in interpulse interval (P0.01). Estrogen implants in the POA caused a small, but nonsignificant (P0.05), decrease in mean LH levels in the first experiment and an increase in LH interpulse interval (P0.05) in the second experiment. These results suggest that the ARC/VMR and possibly the POA are sites at which E acts to reduce GnRH secretion in male sheep.

The final common pathway controlling reproductive function in vertebrates is the GnRH neuron and its projection to the median eminence (ME), site of peptide release into the pituitary portal system. GnRH neurons are widely distributed; therefore we sought to test the hypothesis that those projecting to the ME are located in specific regions. We used as a model the sheep, a species in which a great deal of information regarding the physiology of GnRH secretion is known. To identify cells projecting to the ME (i.e., neuroendocrine neurons), ewes (n = 10) received injections into the ME of neuronal tract-tracing compounds: cholera toxin-beta subunit (CT-beta) or one of two fluorescent compounds (rhodamine isothiocyanate or fluorescein-conjugated dextran). Forty-eight h later, animals were perfused intracranially and their brains were processed for immunocytochemical localization of GnRH and CT-beta using a dual-immunofluorescent procedure or by single-label immunofluorescent visualization of GnRH combined with direct visualization of fluorescent tracers. Small, well-circumscribed injections into the ME were made successfully in 6 of 10 animals, and these overlapped the location of GnRH terminals and fibers. Neuroendocrine GnRH neurons (those GnRH neurons containing retrogradely transported tracer) were identified throughout their previously reported range: within the diagonal band of the Broca/medial septal region, medial preoptic area (MPOA), anterior hypothalamic area, and medial basal hypothalamus. Although the absolute number of neuroendocrine GnRH neurons varied by region, the percentage of the total GnRH population within each of these areas that was retrogradely labeled did not differ (p0.05). Injections placed unilaterally within the ME labeled a similar proportion of GnRH cells both ipsilateral and contralateral to the injection site in all areas except the MPOA, where ipsilaterally labeled cells were approximately twice as numerous as those labeled contralaterally. Injections that missed the ME and were placed either into the third ventricle or into the arcuate nucleus labeled only 0.5% and 4-11% of GnRH neurons, respectively. These results do not support the hypothesis that in the ewe, GnRH neurons projecting to the ME are localized to specific regions. Thus, we postulate that GnRH release into the hypophyseal portal system reflects the output of GnRH neurons located in multiple areas.

The quality of medical care provided to patients with different types of health insurance coverage has only recently begun to be evaluated. Very few studies have compared the process or outcome of care for cancer. Breast cancer is a good disease to use in medical effectiveness studies because it is relatively easy to diagnose with available technology and is treated effectively if detected early. The primary objectives of this study were to compare type of treatment, stage at diagnosis, and survival for female breast cancer patients newly diagnosed through fee-for-service with third-party coverage or health maintenance organization plans offered by the same medical practice during the same time period. Using a historical cohort design, data from a tumor registry were used to compare type of treatment, stage at diagnosis, and survival for 425 patients diagnosed from 1984 through 1992; 53.6% were members of a health maintenance organization and 46.4% used a variety of fee-for-service plans. Overall, there was no difference between the two groups in type of treatment, stage at diagnosis, or survival. Using fee-for-service as the reference group, Cox regression analysis showed that the unadjusted mortality rate ratio for survival was 0.66 (95% confidence interval = 0.432-1.020), and the rate ratio adjusted for age, race, and stage was 0.80 (95% confidence interval = 0.505-1.257). It was concluded that, despite differences in the type of health insurance coverage, there do not appear to be systematic differences in medical outcomes for breast cancer among women who are treated by the same medical care provider. These findings are of interest in the context of the rapidly changing organization of medical care with its implications for clinical practice and for the quality of care offered to patients with different types of medical insurance coverage.

The extent to which inhibitory effects of testosterone (T) on LH secretion in the ram are mediated by its metabolite dihydrotestosterone (DHT) is unknown. Our objective was to determine the effect of inhibiting 5 alpha-reductase activity on pulsatile patterns of LH release in castrated, T-treated male sheep. Nine Dorset and six Hampshire castrated male sheep were allocated equally to one of three treatment groups: 1) infusion of T (768 micrograms/kg/day), 2) infusion of the reductase inhibitor (RI) L-651,723 (0.6 mg/kg/day), and 3) T+RI infusion. Treatments were continuously infused for 3 days. Blood samples were collected via an indwelling jugular catheter at 10-min intervals for 4 h immediately prior to (Day 0) and during the final 4 h of infusion (Day 3). Changes in mean LH, LH pulse amplitude, LH interpulse interval (IPI), T, 17 beta-estradiol (E), and DHT were derived for each animal by subtracting values for Day 0 from Day 3. Data were subjected to one-way analysis of variance. The increase in T and E after infusion of T was similar (p0.10) in T- and T+RI-treated males and greater (p0.01) than in RI-treated males. The increase of DHT was greater (p0.01) in T-treated than either T+RI- or RI-treated males whereas the change was similar (p0.10) for T+RI- and RI-treated males. T decreased mean LH more (p0.01) than RI. T+RI suppressed mean LH more (p0.01) than RI but not as much (p0.01) as T alone.(ABSTRACT TRUNCATED AT 250 WORDS)

The apparent earlier onset of seasonal breeding activity of adult male versus adult female sheep suggests that the neuroendocrine mechanisms that control onset of the breeding season may be sexually differentiated in this species. However, it is difficult to compare gradual onset of testicular growth to abrupt changes in ovarian activity. To determine the relative timing of seasonal transitions in neuroendocrine reproductive activity, we compared temporal changes of LH concentrations in adult, gonadectomized, estradiol (E)-treated (experiment 1), or testosterone (T)-treated (experiment 2) Suffolk male and female sheep held outdoors for 18 mo. In addition, we compared the rates at which E-treated males and females become photorefractory to a winter solstice hold (WSH) photoperiod. In all three experiments, blood samples were collected weekly. In addition, serial blood samples were collected every 12 min for 4 h at approximately 2-mo intervals for experiment 1 and at monthly intervals for experiment 2. Neither plasma E nor T concentrations differed (p0.05) between sexes. In E-treated animals, mean LH changed (p0.001) over time in both sexes, and there was a sex x time interaction (p0.001). LH pulse amplitude changed (p0.001) over time in both sexes, but there was no detectable (p0.05) sex x time interaction. LH pulse frequency varied significantly over time in E-treated females (p0.001) but not in males (p0.05). The amplitude of the annual oscillation of mean LH was greater (p0.01) in E-treated females than in males.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied chromosomal alterations in the peripheral blood lymphocytes of 10 individuals with colorectal polyps and 10 asymptomatic first-degree relatives of patients with colon cancer or colorectal polyps. The analysis was performed on T-lymphocytes using short term blood cultures and on B-lymphocytes by establishing lymphoblastoid cell lines by Epstein-Barr virus transformation. Chromosomal changes were not common in T- and B-lymphocytes. Chromosomes 1 and 5 were most frequently involved in numerical or structural changes in the patients with polyps as well as in the asymptomatic relatives. These alterations were observed in either the T-lymphocytes or the B-lymphocytes but rarely in both, thus accentuating the importance of studying both the cultures concurrently. Chromosome 5, which is known to play an important role in the development of adenomatous polyps, was found to be involved in 6 (60%) of 10 patients with polyps and 4 (40%) of 10 asymptomatic relatives. These findings show that lymphocytic chromosomal analysis can aid in identifying individuals who are genetically susceptible and are at a higher risk of developing colorectal cancer. Because lymphocytic chromosomal analysis is relatively simple and inexpensive, we expect that it will be very useful in screening asymptomatic individuals who are at a higher risk due to inherited or environmental factors.

Cytogenetic analysis of peripheral blood lymphocytes of 19 colorectal cancer patients was carried out in short term blood cultures (T-cells) as well as in Epstein-Barr virus transformed B-cell lymphoblastoid cell lines. One hundred Giemsa-banded metaphases from the T lymphocytes and 50 metaphases from the B lymphocytes of each patient were evaluated for cytogenetic abnormalities. Clonality was not observed in every paired sample. Structural and/or numerical aberrations were most frequent in chromosomes #1, #2, #5, #7, #9, #12, #14, #17, #18 and #21. Aberrations among these chromosomes could be observed individually in either of the cultures, which proves that the analysis of both cultures (T and B cells) is complementary to each other. In some cases involving multiple primary cancers it was interesting that the specific chromosomal change, crucial for a particular malignancy, was identified only in the lymphoblastoid cell line analysis. This supports the notion that B-cell analysis can serve as a useful adjunct to the study of short-term blood cultures and also poses a question as to whether the specific chromosomal changes observed in the analysis are confined to the B-cell lineage.

In this study we examined the relationship between GnRH, LH, and testosterone (T) in intact rams during the nonbreeding season, the breeding season, and the transition between breeding and nonbreeding season. Blood was collected from the hypophyseal portal and jugular veins at 10-min intervals for 12 h from 3 groups of rams in May, September, and March. Individual LH pulses in May and September occurred at relatively regular intervals whereas in March, groups of pulses were separated by relatively long intervals without pulses. No significant effect of season on GnRH pulse parameters was found, but there was a significant effect of season on LH (p0.04) and T (p0.001) pulse amplitude and on mean T concentrations (p0.001). LH pulse amplitude was highest in March, and T pulse amplitude was highest in September. Simple indices of pituitary and testicular responsiveness were obtained by calculating the ratios of LH to GnRH and T to LH. The ratio of LH to GnRH pulse amplitude was significantly higher in March than in September (p0.01) or May (p0.05). The ratio of T to LH pulse amplitude was highest (p0.01) in September. Release of LH in response to exogenous GnRH also varied significantly (p0.01) with month, being higher in March than in September (p0.01) or May (p0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

We previously demonstrated that protein kinase C (PKC) activators, i.e. L-alpha-1,2-dioctanoyl glycerol (C8) and phorbol 12-myristate 13-acetate (PMA), mimic the stimulatory effects of GnRH on both LH glycosylation and release. To further evaluate the roles of PKC, we determined: 1) the interaction between PKC activator and GnRH; and 2) the effects of depleting cellular PKC with a high dose of PMA on LH glycosylation vs. release. Anterior pituitaries excised from ovariectomized rats were enzymatically dispersed and cultured. In series 1 experiments, day 3 monolayer cells were incubated in the presence of radiolabeled precursors and GnRH (0, 1, or 100 nM), with or without C8 (200 microM). In series 2 experiments, day 2 cells were pretreated with either PMA (1 microM) or vehicle (0.08% dimethyl sulfoxide) for 24 h and then incubated with diluent, GnRH (1 nM), or PMA (20 nM), and radiolabeled precursors for 4 h. LH translation and glycosylation were monitored by measuring incorporation of [14C]alanine ([14C]A) and [3H]glucosamine ([3H]GA), respectively, into LH. Immunoreactive LH (IRLH) was measured by RIA. In series 1 experiments, C8 increased basal release of IRLH, potentiated IRLH release stimulated by 1 nM GnRH, but not by 100 nM GnRH. C8 elevated total [3H]GA-LH but had no additive effects with GnRH. In series 2 experiments, PMA pretreatment inhibited subsequent PMA-stimulated IRLH release. However, PMA pretreatment did not affect GnRH-induced IRLH release even though PMA pretreatment decreased cellular IRLH content. In comparison, PMA pretreatment reduced both GnRH- and PMA-stimulated total [3H]GA-LH. PMA pretreatment had no effects on total [14C]A-LH in the presence of GnRH or PMA, but reduced the basal level. In summary, PKC activators had no additive effects on either IRLH release or LH glycosylation stimulated by a maximal dose of GnRH. However, PMA pretreatment decreased GnRH-induced LH glycosylation without depressing LH release. These results suggest differential roles of PKC in the actions of GnRH on LH glycosylation vs. LH release.

This study assessed the effectiveness of two types of health plans, offered by the same health care provider, in the diagnosis and treatment of colorectal cancer. Data on 330 cases diagnosed from 1984 through 1989 were abstracted from medical records. Of these, 205 (62%) used fee-for-service (FFS) and 125 (38%) used health maintenance organization (HMO) plans. Overall, there were no differences between FFS and HMO cases for duration of symptoms before diagnosis, training of physician who diagnosed the tumor, anatomic location of the tumor, type of primary treatment, Dukes' stage at final diagnosis, or survival. There were differences between the groups for age, presence of symptoms at diagnosis, time from detection to treatment, and method of detection. Cox regression analysis showed no difference in survival by type of health plan before or after adjusting for age and stage at diagnosis. The findings from this study are consistent with those from studies reporting little or no difference in the process or outcome of care for patients with different types of medical insurance coverage.

The objective of this study was to determine whether two photoperiod regimens that induce anestrus in the ewe-short-day photorefractoriness (SDPR) and long-day photosuppression (LDPS)--act by different neuronal mechanisms. In separate experiments, ovary-intact (INTACT), ovariectomized (OVX), and ovariectomized estradiol-treated (OVX + E) ewes were subjected to three different photoperiodic regimens that resulted in reproductive quiescence: (1) exposure to long days (16L:8D), which caused photosuppression (INTACT, n = 9; OVX, n = 6; OVX + E, n = 5; (2) prolonged exposure to short days (10L:14D)), which caused photorefractoriness (INTACT, n = 10; OVX, n = 6; OVX + E, n = 5); (3) exposure to natural photoperiod, which induced seasonal anestrus (INTACT, n = 11; OVX, n = 6; OVX + E, n = 5). Effect of photoregimen was monitored by measuring progesterone or LH. Drug challenges were made after two sequential estrous cycles were missed in INTACT ewes, after mean LH concentrations dropped below 1 ng/ml in OVX + E ewes, and after LH interpulse intervals increased in OVX ewes. Effects of drug on LH pulse pattern were determined by taking blood samples at 12-min intervals for 8 h after i.v. diluent injection; then for 8 h after i.v. injection of cyproheptadine, a serotonin antagonist (3 mg/kg); and again 7 days later after i.v. injection of diluent or pimozide, a dopamine antagonist (0.25 mg/kg). Cyproheptadine had little effect except to decrease (p = 0.05) mean LH in INTACT anestrous ewes and decrease (p less than 0.01) pulse amplitude in OVX + E SDPR ewes. Pimozide did not affect LH pulse frequency in LDPS ewes. However, pimozide increased LH pulse frequency (p less than 0.005) and mean concentrations (p less than 0.005) in SDPR OVX + E ewes, whereas it suppressed LH pulse frequency (p less than 0.05) and amplitude (p less than 0.03) in SDPR INTACT and SDPR OVX ewes. The results suggest that (1) the role of the dopaminergic system differs in SDPR and LDPS ewes, and that different neuronal systems may effect SDPR and LDPS, (2) the effect of pimozide in SDPR ewes is altered by ovarian steroids, and (3) the serotonergic system has relatively little role in regulating pulsatile LH secretion in any of the three different states of anestrus.

Data from a multiethnic sample of women participating in the American Cancer Society 1987 Texas Breast Screening Project was used to compare attitudes and behaviors related to breast cancer screening for whites, blacks, and Hispanics. In general, similar patterns of association were observed across racial/ethnic groups between a number of demographic and risk factors and prior mammography and recent clinical breast examination (CBE), although the magnitude of the associations varied somewhat across groups. Reasons for not having had prior mammography also were similar across groups, with lack of physician referral and cost cited as the two most important reasons. However, Hispanics were less likely than blacks or whites to report prior breast cancer screening, including mammography, CBE, and breast self-examination (BSE). This study demonstrated that women of different racial/ethnic backgrounds can be successfully recruited to participate in a patient-initiated, community-based program. However, this programmatic approach requires augmentation with other intervention strategies designed to reach low-income women because women with more years of education and higher family income were overrepresented in all three groups.

Fast wave current drive (FWCD) experiments at 60 MHz are being performed on the DIII‐D tokamak for the first time in high electron temperature, high β target plasmas. A four‐element phased‐array antenna is used to launch a directional wave spectrum with the peak n∥ value (≂7) optimized for strong single‐pass electron absorption due to electron Landau damping. For this experiment, high power FW injection (2 MW) must be accomplished without voltage breakdown in the transmission lines or antenna, and without significant impurity influx. In addition, there is the technological challenge of impedance matching a four‐element antenna while maintaining equal currents and the correct phasing (90°) in each of the straps for a directional spectrum. In this paper we describe the performance of the DIII‐D FWCD antenna during initial FW electron heating and current drive experiments in terms of these requirements.

The DNA content of 53 primary and locally metastatic pulmonary neuroendocrine carcinomas was retrospectively determined by flow cytometric analysis of nuclei released from paraffin-embedded tissues and compared with histologic subtypes and clinical survival. Forty-one percent (9 of 22) of tumors classified as well-differentiated neuroendocrine carcinoma (WDNC) were aneuploid. In contrast, 85% (17 of 20) of small cell neuroendocrine carcinoma (SCNC), and 73% (8 of 11) of intermediate cell neuroendocrine carcinoma (ICNC) were aneuploid. DNA content was not a significant independent predictor of patient survival within each histologic subtype (P greater than 0.05 for all subtypes). Yet, when all cases were examined as a single group, diploid cases showed better clinical survival than cases with DNA aneuploidy (P less than 0.02). However, the survival advantage for diploid DNA content did not quite achieve statistical significance when only cases of limited stage disease were analyzed (0.10 greater than P greater than 0.05). Histologic subtype was also a prognostic indicator, with WDNC cases showing a significantly longer survival than either SCNC (P less than 0.05) or ICNC (P less than 0.02), for those cases with limited-stage disease. These results indicate information on clinical staging and the histologic subtype are important parameters to compare with DNA content analysis in determining independent prognostic factors in neuroendocrine or small cell carcinoma of the lung.

The objective was to determine the effect of chronic testosterone (T) treatment on GnRH and LH secretion in wethers. Rams were either castrated only or castrated and immediately treated with Silastic implants containing T. Several weeks later, a device for collecting hypophyseal-portal blood was surgically implanted. Six to seven days later, blood samples were collected simultaneously and continuously from the portal vessels and jugular vein of pairs of conscious animals. Samples were divided at 10-min intervals for 6-12 h. One hour before the end of collection, all animals received i.v. injections of 250 ng of GnRH. In samples collected simultaneously from 6 pairs of animals, T reduced the frequency of both GnRH pulses (1.8 +/- 0.2 vs. 0.9 +/- 0.3/h, p less than 0.03) and LH pulses (1.6 +/- 0.1 vs. 0.8 +/- 0.3/h, p less than 0.03). T did not alter amplitude of either GnRH or LH pulses. Testosterone reduced mean GnRH (9.7 +/- 0.6 vs. 7.9 +/- 0.5 pg/ml, p less than 0.05), whereas mean LH was not significantly reduced (9.6 +/- 1.4 vs. 6.1 +/- 1.8 ng/ml, p = 0.16). These results support the hypothesis that T reduces GnRH pulse frequency.

Peripheral blood lymphocyte cultures from 23 individuals with polyps and 10 age-matched controls were cytogenetically studied. Of 23 individuals with polyps, 13 were males and 10 females. The age distribution of these patients was between 22 and 84 yr, with a medium age of 49.6 yr. Chromosome 5 was involved in structural rearrangements in 10 of the 18 patients with adenomatous polyps (55.5%). All those who showed involvement of chromosome 5 alterations had either adenomatous polyps or Gardner's syndrome, and two had colon adenocarcinoma. Of the remainder who did not show involvement of chromosome 5, eight had adenomatous polyps and five had hyerplastic polyps (non-neoplastic). Of the 10 control samples, only one showed alteration of chromosome 5. Of the 10 adenomatous polyp subjects that showed chromosome 5 defects, two had translocations of chromosome 5 and the short arm of 17. Chromosome 5 was broken 13 times (5 times in the q arm and 8 times in the p arm). Based on our present cytogenetic data, we tentatively conclude that lymphocyte metaphases may be used to identify colon cancer-predisposed individuals.

Constitutional chromosome abnormalities that may predispose a group of individuals to develop certain neoplasms have been reported for some human solid tumors. Deletions of 13q in retinoblastoma, 11p in Wilms' tumor, 1p in neuroblastoma, 3p in renal cell carcinoma, 5q in colorectal carcinoma and 22q in meningioma are examples of such anomalies. In breast carcinoma, a specific cytogenetic defect has not been conclusively identified. We have studied Phytohemagglutinin-stimulated lymphocytes of 76 breast cancer patients, 68 predisposed family members, 40 controls, and 30 additional controls with lung cancer to determine whether nonrandom chromosome defects are present. From each sample 100, G-or Q-banded metaphase spreads were studied for rearrangements. A marked clustering of alterations in the long arm of chromosome no. 1 (q11-22) was seen in breast cancer patients and in some predisposed family members. Alterations in 1q were present in 1% to 3% of metaphases, and included translocations to chromosomes 3, 6, 7, 9, 12, 15, 17, 18, 21 and the X; deletion of 1q, or pericentric inversion. Twelve out of 62 (19.3%) familial cases, 3 out of 14 (21.4%) sporadic cases, 9 out of 68 (13.2%) predisposed cases and 2 out of 40 (5%) control cases showed 1q alterations. None of the 30 lung cancer patients showed chromosome 1 anomaly in this region. This is consistent with the reports on primary breast tumor tissues, cell lines and pleural effusions where 1q defects have been reported. We conclude that chromosome 1q rearrangement might be one of the primary lesions specifically associated with the development of breast cancer.

Circulating concentrations of prolactin were monitored for 3 yr in intact ewes kept either outdoors or indoors in a fixed equatorial photoperiod (12L:12D) and restricted range of environmental temperatures. Prolactin data were analyzed by spectral analysis. In all ewes kept outdoors, concentrations of prolactin showed robust circannual rhythms with a single predominant period of 359 days. In ewes kept indoors, the range of significant periods varied from 35 to 532 days. Although all ewes kept indoors showed a significant rhythm with a period of 354 days, this clearly was not the predominant period in all. The amplitude of the rhythm in ewes kept indoors was significantly lower (p less than 0.01) than that of ewes kept outdoors. Although the annual rhythm of circulating prolactin typical of ewes kept outdoors was significantly compromised in animals kept under a constant 12L:12D photoperiod and restricted environmental temperature range, there was evidence of an endogenous circannual rhythm.

A family in which the proband (father) has multiple polyposis coli associated with Gardner's syndrome and his only son, also with multiple polyps, has been studied cytogenetically. The karyotypes of the proband and the son have shown deletion in the short arm of one chromosome 12 in a small percentage of cells. Normal cells and cells with a deletion of a 12p were noted, not only in the lymphocytes, but also in the skin fibroblast culture of the son. The karyotypes of the asymptomatic mother and their unaffected daughter were considered to be normal.

The objective was to determine if "clamping" ewes onto a 12L:12D photoperiod resulted in expression of circannual rhythms of reproductive activity. On 24 February, 1986, two groups of 6 yearling ewes each were placed in isolated adjacent photochambers under a 12L:12D photoperiod and controlled temperature. Six control ewes were kept outdoors. Blood samples taken thrice weekly were analyzed for progesterone. Data from Days 0-1056 are reported. The mean number of cycles by control and 12L:12D ewes did not differ (32.8 +/- 1.7 vs. 29.7 +/- 4.0). The ranges were 27-39 vs. 4-51, respectively. Ten 12L:12D ewes started cycling coincidentally or later than the controls, and then cycled either regularly or irregularly throughout the study. Two of the 12L:12D ewes cycled continuously. The mean number of cycles during the period 15 April-15 August (anestrus) in Years 1, 2, and 3 were 0.7, 0.7, 0.2 for controls versus 0.3, 5.1, and 4.5 for 12L:12D ewes. The mean number of cycles during the period 15 September-15 January (breeding season) in Years 1, 2, and 3 were 7.3, 7.7, and 7.3 for controls versus 2.8, 4.8, and 4.0 for 12L:12D ewes. All controls showed distinct, alternating annual periods of anestrus and ovarian cycles whereas only two 12L:12D ewes showed a similar pattern. Estrous cycles were distributed nonrandomly in all controls and in 2 ewes exposed to 12L:12D. In the 12L:12D ewes, melatonin concentrations rose immediately after the lights-off and fell immediately after on. Lengths of the luteal phases of the cycles did not differ between groups. In summary, estrous cycles of most ewes clamped on a 12L:12D photoperiod occurred throughout the year at variable intervals rather than in distinct breeding seasons.

In this study we attempted to dissociate big LH (BLH) into low molecular weight forms by treatment with either ribonuclease or mercaptoethanol. We compared the molecular nature of BLH and native LH (NLH) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Also, we explored the relationship between BLH and NLH by both continuous and pulse-chase labeling techniques on the premise that BLH represents a precursor to NLH. During the pulse periods, [‘4C1-alanine-Iabeled BLH was detected in the tissue before [‘4C)-NLH, and then the amounts of both forms increased linearly with time. At all times, the percentage of total 114C) -LH as BLH remained very high. �3 HJ-Glucosamine-labeled BLH and NLH were detected coincidentally in the tissue, and then 1� H)-BLH increased at a constant rate, whereas 1� H]-NLH increased at an increasing rate with time. The percentage of total �3 HJ-LH as BLH declined with time. The magnitude of change of radiolabeled LH varied with conditions during the chase periods, but similar trends were observed in all experiments. During the chase, (� Cl -BLH decreased

The ability of 67Ga citrate and 99mTc pyrophosphate cardiac imaging to detect myocarditis was assessed in an experimental rabbit model. Twenty-three rabbits were imaged approximately 72 hours after infusion of i.v. norepinephrine. Diffuse cardiac uptake was found in 13 of 15 rabbits scanned with 67Ga. Tissue distribution studies documented significant myocardial uptake of 67Ga in those with positive scans. Precordial imaging and tissue distribution studies revealed no cardiac uptake in the eight rabbits scanned with 99mTc. Histologic examination of all 23 hearts revealed qualitatively similar, typical lesions of myocarditis. This study suggests that cardiac imaging with 67Ga may be useful in the detection of myocarditis.

We examined basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release and synthesis in response to drugs that raise intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. Anterior pituitaries from ovariectomized rats were incubated with or without drugs in the presence of GnRH and [3H]glucosamine. Neither 8-bromo-cAMP (8-Br-cAMP) (10 mM), cholera toxin (10 micrograms/ml), nor phosphodiesterase inhibitors [theophylline, 2 and 8 mM; 3-isobutyl-1-methylxanthine (MIX), 0.2 mM] had any detectable effect on release of immunoreactive LH (IR-LH) when used alone. However, 8-Br-cAMP and the inhibitors potentiated (P less than 0.01) GnRH-induced release of IR-LH. Total radiolabeled LH in the system was elevated (P less than 0.01) by either GnRH, 8-Br-cAMP for cholera toxin, but reduced (P less than 0.01) by 8 mM theophylline and unaffected by MIX or 2 mM theophylline. 8-Br-cAMP did not alter the effect of GnRH on radiolabeled LH in the total system, whereas MIX and 2 mM theophylline reduced (P less than 0.05) it. These results suggest that 1) cAMP does not effect LH release directly, but may interact with GnRH to potentiate it, 2) GnRH and cAMP have a similar mode of action on LH glycosylation, and 3) phosphodiesterase inhibitors have additional actions that interfere with LH glycosylation.

The DIII-D high and low beta stability results have established the basic feasibility of the divertor and H-mode configurations up to elongation 2.0 for next generation tokamaks. The 6.8% beta T achieved has already exceeded projected operating requirements of next generation devices. beta T > 6% has been sustained for 800 ms. Stability calculations and patterns of MHD mode behavior suggest a central expanding zone of ballooning instabilities leads ultimately to unstable m/n=2/1 modes which cause beta collapse or disruption. The pressure gradient at the plasma edge just reaches the first regime ballooning limit prior to ELMs. ECRH has proven effective for generating H-mode, sawtooth suppression, and ELM suppression.

The first year of operation of Doublet III, a large noncircular tokamak (R=1.43 m, a=0.45 m, BT ≤2.6 T), was highlighted by the achievement of a plasma current in excess of 2 MA. This is partially attributed to the low Zeff discharges made possible by wall conditioning using low temperature, low power discharge cleaning, accompanied by preconditioning of the wall and by baking. Approximately 500 h of hydrogen discharge cleaning and 25 h of oxygen discharge cleaning combined with tokamak plasma operations were required to obtain these low Zeff tokamak discharges. During the initial cleanup of the wall, copious quantities (>100 monolayers) of carbon were removed, ultimately with greatest efficiency by oxygen discharge cleaning. During the conditioning process, monitoring the impurity removal rate with the residual gas analyzer (RGA) provided the most understandable measure of the rate of the cleanup, while an in situ Auger analysis surface diagnostic supplied and operated by ORNL was most useful in identify...

Vacuum integrity of large fusion tokamaks has become increasingly important as the complexity and requirements for cleanliness have increased. Doublet III is a large noncircular tokamak (R = 1.43 m, V = 27 m3) designed for a base pressure of 2×10−8 T and a leak rate of 5×10−6 T⋅l/s. Initial leak testing of the vacuum chamber used conventional techniques. After final assembly, leak testing became more difficult as diagnostic systems, coil systems, and heating blankets enveloped the vacuum vessel. Methods were developed to locate and quantify vacuum leaks in this difficult environment. A residual gas analyzer was used for temporal response to gases flowed at various points outside the vessel. Leaks occurring in the primary vessel wall were measured by pumping on gas cooling channels adjacent to the primary vacuum wall. Air in these channels was also displaced by other gases at a constant rate to give location of leaks to within 50 cm. Vacuum leaks occurred during machine operations due to applied stresses, plasma‐material interactions, and diagnostic equipment failures. Machine vents to fix these leaks involve a significant loss of time, particularly in returning to clean wall conditions. Methods other than venting the vessel have been used, such as helium ’’patches,’’ if these leaks are sufficiently small.

We determined if luteinizing hormone (LH) synthesis is Ca2+ dependent and coupled to LH release. We monitored LH synthesis when LH release was stimulated either by specific [gonadotropin-releasing hormone (GnRH)] or nonspecific stimuli (50 mM K+ and 2 or 20 microM Ca2+ ionophore A23187) and inhibited by Ca2+-reduced medium. LH synthesis was estimated by measuring incorporation of [3H]glucosamine (glycosylation) and [14C]alanine (translation) into total (cell and medium) immunoprecipitable LH by cultured rat anterior pituitary cells. Both GnRH (1 nM) and 50 mM K+ significantly stimulated LH release and glycosylation, but had no effect on LH translation. A23187 also stimulated LH release, but significantly depressed glycosylation of LH and total protein and [14C]alanine uptake. Deletion of Ca2+ from the medium depressed both GnRH-induced LH release and glycosylation. Addition of 0.1 mM EGTA to Ca2+-free medium not only inhibited GnRH-induced release and glycosylation of LH but also uptake of precursors and glycosylation and translation of total protein. Thus glycosylation and release of LH are Ca2+ dependent. Whether parallel changes in LH release and glycosylation reflect a cause and effect relationship remains to be determined.