A 2-4 keV multilayer mirrored channel for the NIF Dante system.

During inertial confinement fusion experiments at the National Ignition Facility (NIF), a capsule filled with deuterium and tritium (DT) gas, surrounded by a DT ice layer and a high-density carbon ablator, is driven to the temperature and densities required to initiate fusion. In the indirect method, 2 MJ of NIF laser light heats the inside of a gold hohlraum to a radiation temperature of 300 eV; thermal x rays from the hohlraum interior couple to the capsule and create a central hotspot at tens of millions degrees Kelvin and a density of 100-200 g/cm3. During the laser interaction with the gold wall, m-band x rays are produced at ∼2.5 keV; these can penetrate into the capsule and preheat the ablator and DT fuel. Preheat can impact instability growth rates in the ablation front and at the fuel-ablator interface. Monitoring the hohlraum x-ray spectrum throughout the implosion is, therefore, critical; for this purpose, a Multilayer Mirror (MLM) with flat response in the 2-4 keV range has been installed in the NIF 37° Dante calorimeter. Precision engineering and x-ray calibration of components mean the channel will report 2-4 keV spectral power with an uncertainty of ±8.7%.

Observation of high soft x-ray drive in large-scale hohlraums at the National Ignition Facility.

The first soft x-ray radiation flux measurements from hohlraums using both a 96 and a 192 beam configuration at the National Ignition Facility have shown high x-ray conversion efficiencies of ∼85%-90%. These experiments employed gold vacuum hohlraums, 6.4 mm long and 3.55 mm in diameter, heated with laser energies between 150-635 kJ. The hohlraums reached radiation temperatures of up to 340 eV. These hohlraums for the first time reached coronal plasma conditions sufficient for two-electron processes and coronal heat conduction to be important for determining the radiation drive.

Prediction of enthalpy and standard Gibbs energy of vaporization of haloaromatics from atomic properties.

Halogenated benzenes form a class of pollutants with a huge number of members - 1504 distinct benzene compounds, where one or more hydrogen atoms are replaced by halogens, may exist theoretically. This study presents a user friendly method for accurate prediction of vapor pressures and enthalpies of vaporization, at 298.15 K, of any mono or poly halobenzene compound. The derived equations for the prediction of those vaporization properties depend just on the number of each constituent halogen atom. This is a consequence of the absence of intramolecular interactions between the halogen atoms, revealed after examining vaporization results of ca. 40 halogenated benzenes. In order to rationalize the estimation equations, the contribution of the halogen atoms for the referred to above properties of vaporization was decomposed into two atomic properties - the volume and electron affinity. Extension of the applicability of the estimation method to substituted benzenes containing other substituent groups beyond halogen atoms as well as to some polycyclic aromatic species was tested with success.

Characterization of recombinant human cathepsin B expressed at high levels in baculovirus.

The lysosomal cysteine protease cathepsin B has been studied intensely for many years because of its unique characteristics and its potential involvement in disease states. A reproducible, high yield expression system for active recombinant protein is key to biochemical and biophysical studies as well as rational drug design. Although several microbial and mammalian expression systems for recombinant human cathepsin B have been described, these have been limited by low or variable yields. Further, in some of these systems hyper-glycosylation of the enzyme near the active site affects its activity. We describe a baculovirus expression system and purification scheme that solve all of these problems. Yields of active, protected enzyme were reproducibly in excess of 25 mg/L. Since this protein was not hyper-glycosylated, it had greater activity than cathepsin B produced in yeast systems as indicated by a threefold increase in Kcat. In addition, the biophysical properties of the baculovirus-expressed cathepsin B, as measured by dynamic light scattering, were more amenable to crystallographic study since the data indicated proteins of more uniform size. Therefore, this system for the production of recombinant human cathepsin B constitutes a major improvement in both quantity and quality over those previously reported. Further, we demonstrate that the manner of expression and purification of this enzyme has profound effects on its kinetic and physical parameters.

Anxiety, anxiolytics and brain stimulation reinforcement.

The premise of this review is that neuronal substrates of anxiety are amenable to investigation using brain stimulation techniques. Anxiolytics such as meprobamate and the benzodiazepines may enhance intracranial self-stimulation (ICSS) behavior. Although demonstrated by numerous investigators, this effect shows considerable variability between and within laboratories. Some of this variability is explained by sedative/muscle relaxant effects, which are dissociable from drug-induced increases in ICSS and which may mask these increases. The anticonvulsant actions of anxiolytic drugs are unlikely to account for the increases in ICSS. Rather, anxiolytics appear to increase ICSS by attenuating concurrent aversive properties of stimulation. Consistent with this explanation, anxiolytic drugs attenuate escape from aversive dorsal tegmental stimulation. The neuronal substrates of this centrally mediated escape behavior differ from those mediating footshock-induced escape. Barbiturates also enhance ICSS, possibly due in part to an excitatory component that is not involved in benzodiazepine action. Inverse benzodiazepine agonists attenuate ICSS behavior in a manner that cannot be explained by nonspecific performance impairment. These substances, however, may not necessarily enhance stimulation-induced aversiveness. A strategy is proposed to integrate brain stimulation studies with molecular approaches to anxiety. Specifically, stimulation of sites associated with fear induction or fear reduction may selectively alter the release of endogeneous anxiogens or anxiolytic substances.

Discriminating between reward and performance: a critical review of intracranial self-stimulation methodology.

Despite numerous pharmacological investigations of intracranial self-stimulation (ICSS), the substrates of this behavior have yet to be completely understood. In view of the likelihood that inadequate methodology has hindered the quest for these substrates, the present review was undertaken. Criteria for ICSS methodology should include not only the ability to discriminate reward from gross performance deficit, but also adequate capacity (ability to generate experimental data at a reasonable rate). For numerous reasons, bar-pressing on a continuous reinforcement schedule fails the first criterion despite its ease and rapidity. The use of partial reinforcement schedules may alleviate some of these shortcomings. Analysis of drug-induced response decrement patterns can discriminate gross motoric incapacity from other variables, although the question of subtle response maintenance deficits remains to be answered. Measurements of response rates using alternative operants do not differentiate reward and performance adequately. More promising, "rate-free" measures using locomotion as an operant include the two-platform method of Valenstein and the "locus of rise" method. Comparison of drug effects on ICSS with those on alternate tasks are fraught with pitfalls including the problems of assuring equivalent rates and patterns of responding. The use of differential electrode placements is ideally suited for neurochemically well-characterized drugs, particularly if "double dissociations" can be established during studies of multiple placements. Presentation of different current intensities or frequencies permits the compilation of rate-intensity functions, and drug-induced shifts in these functions have considerable analytical power. Self-regulation of current intensity constitutes a powerful tool that has yet to realize its full potential in the pharmacological study of ICSS. Extensive studies involving self-regulation of stimulation duration ("shuttlebox" studies) suggest that this method may be highly versatile despite several practical difficulties. It is concluded that at least six of these methods appear to do a reasonable job of excluding gross performance deficit. However, the possible influences of other factors, such as subtle response maintenance deficit, incentive or arousal, remain to be resolved in view of the multifactorial nature of ICSS. Multiple tests for ICSS drug or lesion studies are advocated whenever feasible, as no single test appears capable of resolving all theoretical complexities.

Aromatic L-amino acid decarboxylase in rat corpus striatum: implications for action of L-dopa in parkinsonism.

We studied the distribution of aromatic L-amino acid decarboxylase (AAAD) activity in striatal compartments of rats. After near-total destruction of nigrostriatal dopaminergic neurons, 15 to 20% of the initial enzyme activity remained. Striatal enzyme activity remained unchanged after destruction of serotoninergic terminals by electrolytic raphe lesions. Combined raphe-nigrostriatal lesions or nigrostriatal lesions alone produced similar decreases in striatal decarboxylase. Intrastriatal injection of kainic acid (which selectively destroys striatal interneurons and efferent neurons and also induces marked glial proliferation) reduced activity by 20%. Only 7% of initial striatal activity (perhaps localized in capillaries) remained after combined nigrostriatal-kainic acid lesions. These findings indicate that after degeneration of dopaminergic terminals, striatal interneurons and efferent neurons, but not serotonergic terminals of glia, contain an important fraction of the residual AAAD. This compartment may be the site of enzymatic conversion of exogenous L-dopa to dopamine in the parkinsonian striatum.

Antinociceptive profile of sulfated CCK-8. Comparison with CCK-4, unsulfated CCK-8 and other neuropeptides.

The antinociceptive activity of sulfated cholecystokinin octapeptide (CCK-8-S) was characterized by comparison with two other endogenous forms, unsulfated CCK-8 (CCK-8-U) and the carboxyl tetrapeptide fragment (CCK-4) and two other peptides present in the gut and brain: bombesin and neurotensin. By the intracerebroventricular (i.c.v.) route, CCK-8-S was antinociceptive in the hot plate and phenylquinone-induced writhing assays, but CCK-8-U and CCK-4 were active only in the latter test. By systemic administration, CCK-8-S retained anti-writhing activity but CCK-8-U and CCK-4 did not. Therefore, CCK receptors in brain may be involved in the apparent antinociception produced by CCK-8-U and CCK-4. Bombesin produced potent antinociceptive activity, along with a distinct, head-scratching syndrome, in both the writhing and hot plate tests. Naloxone reversed bombesin-induced elevation of latencies of mouse jump but not the head-scratching syndrome, indicating that the analgesic effect in the hot plate test was independent of the scratching behaviour. Neurotensin, unlike CCK-8-S, elevated tail-flick latencies, and was more potent in the writhing than in the hot plate test. Several differences between CCK-8-S and opioid substances included the need for relatively large doses of naloxone to block the effects of CCK-8-S in the phenylquinone-induced writhing test and the lack of effect of CCK-8-S in the tail-flick test. Global sedation can account for some, but not all, of the effects of CCK-8-S.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal circulatory changes: an echocardiographic study.

Serial echocardiograms were performed in the first three days of life on 38 normal full-term infants. Right ventricular systolic time intervals were measured from the pulmonic valve echogram and left ventricular systolic time intervals were determined from the aortic valve echogram. The heart rate, left ventricular pre-ejection period (LPEP), left ventricular ejection time (LVET), and LPEP/LVET ratio showed insignificant variation with increasing postnatal age. The right ventricular pre-ejection period (RPEP) shortened, the right ventricular ejection time (RVET) lengthened, and the RPEP/RVET ratio decreased with increasing age. The findings suggested that alterations in the RPEP/RVET ratio reflected the decreasing pulmonary artery diastolic pressure and pulmonary vascular resistance of the early neonatal period and may be valuable in the noninvasive evaluation of the newborn's pulmonary vascular bed.

Echographic ventricular systolic time intervals in normal term and preterm neonates.

Right ventricular and left ventricular systolic time intervals (RVSTIs and LVSTIs) were measured in normal term and preterm infants from 1 hour to 90 days of life. LVSTIs in both term and preterm infants were similar in the first five days of life. The ratio of left pre-ejection period (LPEP) to left ventricular ejection time (LVET) was lower in preterm infants older than age 5 days. Estimated gestational age had no influence on LVSTI. The ratio of right pre-ejection period (RPEP) to right ventricular ejection time (RVET) was lower in preterm infants (0.32) than in term newborns (0.37). The preterm RPEP/RVET ratio decreased with age, but at a slower rate than in term babies. This was consistent with the lower pulmonary vascular resistance present in preterm infants.

Respiratory distress syndrome: echocardiographic assessment of cardiovascular function and pulmonary vascular resistance.

Echocardiograms were performed for 82 preterm infants comprising 22 normal infants, 29 with mild respiratory distress syndrome (RDS), and 31 with severe RDS. Left ventricular systolic time intervals were measured from aortic valve echograms and right ventricular systolic time intervals from pulmonic valve echograms. Left ventricular performance seemed to be altered early in postnatal adaptation of preterm infants, but played no demonstrable role in the outcome of RDS. The right ventricular preejection period/right ventricular ejection time (RPEP/RVET) ratio was prolonged in 17 out of 31 patients with severe RDS, consistent with increased pulmonary vascular resistance or right ventricular dysfunction. Prolonged RPEP/RVET identified a subgroup with increased mortality and morbidity.

Studies on cor pulmonale in cystic fibrosis: I. Effects of diuresis.

The effects of acute diuresis in patients with cor pulmonale secondary to cystic fibrosis were studied. Both hemodynamic parameters and arterial blood gas changes were investigated. The major effect noted was a significant reduction of systemic venous pressure. Pulmonary artery and pulmonary artery wedge pressure either remained constant or declined slightly. No consistent changes were noted in cardiac output or arterial blood gases. Acute diuresis of moderate degree appears to be a safe and effective manner in which to treat the systemic venous congestion of cor pulmonale in this situation.

Echocardiographic assessment of the adequacy of pulmonary arterial banding.

Thirty-one echocardiograms of 21 patients who had pumonary arterial banding were analyzed to assess the aequacy of surgery. In 5 patients the echocardiograms were obtained before and after banding and in 16 patients only after surgery. Right and left ventricular systolic time intervals were measured echographically. The ratios of the right ventricular preejection period to right ventricular ejection time (RPEP/RVET) were correlated with both diastolic (r = 0.94) and systolic (r = 0.86) pulmonary arterial pressures distal to the band. The analysis of right ventriclar systolic time intervals, especially the RPEP/RVET ratio, clearly differentiated patients with an adequate band (distal pulmonary arterial diastolic pressure less than 15 mm Hg) from patients with an inadequate band (distal pulmonary arterial diastolic pressure equal to or greater than 30 mm Hg). The results indicate that echocardiography is a useful noninvasive tool in evaluating the adequacy of the pulmonary arterial band and facilitates the follow-up of patients after banding.

Surgical therapy for congenital aortic valvular stenosis. A 23 year experience.

This is a review of 70 consecutive patients (2 to 20 years old) who underwent valvotomy for congenital aortic valvular stenosis from 1958 through 1980. A tricuspid valve was created in 36, a bicuspid valve in 33, and a valve prosthesis was inserted in one, with two operative deaths (2.8%). There were four late deaths, three due to noncardiac causes. Eleven patients required reoperation from 2 to 21 years (mean 11.3 years) after valvotomy, with two deaths. Seven patients underwent valve replacement. One patient died 9 years after a second valvotomy. The overall survival rate including reoperation was 92.6% for 10 years and 86% for 15 years. Of 53 surviving patients free of reoperation, 49 are in New York Heart Association Class I and four are in Class II. One of the patients in Class II is a candidate for reoperation. The other 52 patients are well. Twenty-three have normal stress tests, and only one of 24 studied has a pressure gradient greater than 50 mm Hg. We concluded from this experience that valvotomy effectively and safely relieves left ventricular outflow tract (LVOT) obstruction produced by congenital aortic valvular stenosis. It delays the time when a prosthetic device will be required to relieve LVOT obstruction.

Hemitruncal sling: a newly recognized anomaly and its surgical correction.

A new type of vascular ring formed by a hemitruncal pulmonary artery is described. Early reimplantation of the hemitruncal pulmonary artery resulted in resolution of the respiratory distress, protection of the pulmonary arterial bed from obstructive vascular disease, and preparation of the pulmonary artery for future surgical correction.

Echocardiographic abnormalities in patients with cystic fibrosis.

An echographic study was undertaken to evaluate left (LV) and right ventricular (RV) function in 30 patients with cystic fibrosis. Echographic recording of the pulmonary and aortic valve echogram permitted measurement of the phases of right and left ventricular systole. The ratio of the LV preejection period/LV ejection time (LPEP/LVET) and shortening of the LV internal dimension %SID was employed to reflect LV function, while RV preejection period/RV ejection time (RPEP/RVET) has excellent correlation with pulmonary artery diastolic pressure. RPEP/RVET and two other echographic measurements, right ventricular wall (RVW) and internal dimension (RVD) were compared with pulmonary function tests and clinical scores. RPEP/RVET correlated well with percent vital capacity(%VC), r = -0.73, percent residual volume (%RVol) r = +0.72, and clinical score, r = -0.77. Multilinear regression of RPEP/RVET, RVD, and RVW improved correlation for %VC (r = -0.80), %RVol, r = +0.82, and clinical score, r = -0.84. Patients in overt right heart failure exhibited elevated RPEP/RVET (mean = 0.48) when compared to patients not in right heart failure (mean = .33). Marked diminution of LV function was present in two patients. A variety of cardiovascular abnormalities were demonstrated echographically and were valuable in assessing the degree of cardiac involvement in patients with cystic fibrosis.

Ventricular interdependence in severe cystic fibrosis. A two-dimensional echocardiographic study.

A variety of mechanisms have been implicated in the development of left ventricular dysfunction in patients with chronic cor pulmonale. A two-dimensional echocardiographic study of cystic fibrosis (CF) patients with severe cor pulmonale was undertaken to evaluate the effects of long-term pulmonary abnormalities on right and left ventricular geometry. Ten patients with severe obstructive pulmonary disease secondary to CF underwent evaluation by a mechanical sector scanner from the long axis, short axis, and four chambered views. All patients manifested right heart failure. Eight had clinical scores less than 40 and died within six months of the initial examination. All patients were receiving diuretics, and six were taking digoxin at the time of the study. The most striking echographic feature was flattening or compression of the left ventricle along its minor dimension by a massively dilated right ventricle. Compression of the left ventricle and additional abnormalities of interventricular septal motion resulted in dyskinetic contraction and relaxation that could contribute to a diminished stroke volume. Massive right ventricular enlargement appears to be a major factor producing left ventricular dysfunction in chronic cor pulmonale.

Comparison of exercise and catheterization results following total surgical correction of tetralogy of Fallot.

Although surgery may correct the hemodynamic abnormalities of tetralogy of Fallot (TOF), the long-term effects on exercise tolerance are uncertain. Twenty-eight patients, aged 7 to 30 years, had cardiac catheterization and maximal graded exercise testing to evaluate the adequacy of the ehmodynamic repair and its relation to exercise performance. Patients were tested 2 to 9 years after operation, and 13 previously had had palliative shunt procedures. At catheterization, 23 of the 28 patients had good surgical results. Despite the satisfactory hemodynamics, maximal working capcity (MWC), maximum heart rate, and exercise blood pressure were diminished when compared to normal values. In 10 patients who had exercise studies at catheterization, right ventricular systolic pressure (RVSP) and residual gradients were magnified by exercise. Abnormalities were independent of age at time of correction, time elapsed since surgery, use of patch in the outflow tract, or any antecedent procedures.

Neuroleptic-induced acute dyskinesias in squirrel monkeys: correlation with propensity to cause extrapyramidal side effects.

In squirrel monkeys that had undergone repeated treatment with haloperidol at intervals of 7--14 days, subsequent acute administration of haloperidol induced dystonia and dyskinesias. This acute effect of haloperidol was dose-related and occurred at the same doses that impaired Sidman avoidance performance. Chlorpromazine, fluphenazine, metoclopramide, tetrabenazine, and Su-23397, all of which have been associated with extrapyramidal side effects, reliably elicited dyskinesias in these monkeys. Dyskinesias were less mared after thioridazine and absent after clozapine, corresponding to the reported lower incidence of extrapyramidal side effects in the clinic. The non-neuroleptics, baclofen, and diazepam, failed to elicit dyskinesias. In contrast to the dyskinetic syndrome, the incidence of catalepsy or tremor did not accurately predict propensity to elicit extrapyramidal symptomatology. The acute dyskinetic syndrome in squirrel monkeys may therefore serve as an animal model for predicting the ability of antipsychotics to cause extrapyramidal dysfunction, and may yield insight into the mechanisms of these drug-induced motor disorders.

Rotational behavior induced by 8-hydroxy-DPAT, a putative 5HT-1A agonist, in 6-hydroxydopamine-lesioned rats.

Rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the ascending nigro-striatal pathway have been shown to rotate in response to dopamine (DA) agonists that are not considered to have postsynaptic DA stimulant properties in intact animals, suggesting a relative loss of DA receptor selectivity in the denervated striatum. The present experiments assessed the possibility that this loss of selectivity may extend to serotonin (5HT) agonist drugs. The 5HT-1a agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), at doses of 0.3-3 mg/kg SC, induced robust contralateral rotational behavior (RB) in 6-OHDA-lesioned rats that had been preselected on the basis of high responsiveness to the atypical DA agonists 3-PPP and SKF 38393. Rats with unilateral dorsal raphe lesions induced by 5,7-dihydroxytryptamine (5,7-DHT) showed contralateral RB in response to similar doses of 8-OH-DPAT but with a different behavioral pattern. The putative 5HT-1b agonist RU 24969 produced contralateral RB in 5,7-DHT-lesioned rats while showing a much weaker effect in 6-OHDA-lesioned rats. Striatal DA levels were depleted by 99% in representative 6-OHDA-lesioned rats but striatal 5HT levels were unaffected. The effects of 8-OH-DPAT in 6-OHDA-lesioned rats were therefore not attributable to destruction of ascending 5HT-containing neurons. These effects may result from indirect actions, mediated by 5-HT neurons or neuronal receptors, that result from asymmetry of brain DA systems.(ABSTRACT TRUNCATED AT 250 WORDS)