Preequilibrium Asymmetries in the

The physical properties of neutrons emitted from neutron-induced fission are fundamental to our understanding of nuclear fission. However, while state-of-the-art fission models still incorporate isotropic fission neutron spectra, it is believed that the preequilibrium prefission component of these spectra is strongly anisotropic. The lack of experimental guidance on this feature has not motivated incorporation of anisotropic neutron spectra in fission models, though any significant anisotropy would impact descriptions of a fissioning system. In the present work, an excess of counts at high energies in the fission neutron spectrum of ^{239}Pu is clearly observed and identified as an excess of the preequilibrium prefission distribution above the postfission neutron spectrum. This excess is separated from the underlying postfission neutron spectrum, and its angular distribution is determined as a function in incident neutron energy and outgoing neutron detection angle. Comparison with neutron scattering models provides the first experimental evidence that the preequilibrium angular distribution is uncorrelated with the fission axis. The results presented here also impact the interpretation of several influential prompt fission neutron spectrum measurements.

Skeletal outcomes by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in adolescent girls with anorexia nervosa.

We conducted the first comparison of dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) outcomes in adolescent girls with anorexia nervosa. We observed deficits in bone density by both tools. pQCT assessments were associated with many of the same clinical parameters as have been previously established for DXA. INTRODUCTION: Adolescents with anorexia nervosa (AN) commonly exhibit bone loss, but effects on bone geometry are less clear. We compared measures obtained by DXA and pQCT in girls with AN. METHODS: Seventy females (age 15.5 ± 1.9 years ) with AN and 132 normal-weighted controls underwent tibial measures by pQCT including trabecular volumetric bone mineral density (vBMD) at the 3 % site, cortical vBMD and dimensions at the 38 % site, and muscle cross-sectional area (CSA) at the 66 % site. Participants with AN also underwent standard DXA measures. Independent t tests compared the pQCT results, while Pearson coefficient assessed correlations among DXA and pQCT measures. RESULTS: Trabecular vBMD Z-scores were lower in AN compared to controls (AN -0.31 ± 1.42 vs +0.11 ± 1.01, p = 0.01) and cortical vBMD Z-scores were higher (AN +0.18 ± 0.92 vs -0.50 ± 0.88, p < 0.001). Trabecular vBMD and cortical CSA Z-scores positively correlated with DXA BMD Z-scores (r range 0.57-0.82, p < 0.001). Markers of nutritional status positively correlated with Z-scores for trabecular vBMD, cortical CSA, section modulus, and muscle CSA (p < 0.04 for all). CONCLUSIONS: This study is the first to compare DXA and pQCT measurements in adolescent girls with AN. We observed deficits in BMD by both DXA and pQCT. pQCT assessments correlated well with DXA bone and body composition measures and were associated with many of the same clinical parameters and disease severity markers as have been previously established for DXA. The differences in cortical vBMD merit further study.

The Effect of Caffeine Ingestion during Evening Exercise on Subsequent Sleep Quality in Females.

In a randomised, double-blind, placebo-controlled crossover design, 10 females taking monophasic oral contraceptives completed 90 min intermittent treadmill-running 45 min after ingestion of 6 mg∙kg(-1) body mass anhydrous caffeine or artificial sweetener (placebo). Water (3 mL∙kg(-1)) was provided every 15 min during exercise. Venous blood samples were taken before, during and after exercise, as well as after sleep (~15 h post-ingestion), and levels of caffeine, paraxanthine, theobromine and theophylline were measured using high-performance liquid chromatography. Sleep quality was assessed using the Leeds Sleep Evaluation Questionnaire. Plasma caffeine concentration peaked 100 min after ingestion. Caffeine clearance was 0.95±0.14 mL·min(-1)·kg(-1) while the elimination half-life of caffeine was 17.63±8.06 h. Paraxanthine and theophylline levels were significantly elevated at 15 h with no significant change in theobromine. Sleep latency and subsequent quality of sleep was impaired following caffeine supplementation (P<0.05); there were no differences between trials for how participants were feeling upon awakening. This is the first controlled study to examine caffeine supplementation on sleep quality in female athletes taking a low-dose monophasic oral contraceptive steroid following an intermittent-exercise running protocol. The data shows that female athletes using monophasic oral contraceptive steroids will have impaired sleep quality following evening caffeine ingestion.

Abrupt change in radiation-width distribution for 147Sm neutron resonances.

We obtained the total radiation widths of s-wave resonances through an R-matrix analysis of (147)Sm(n,γ) cross sections. Distributions of these widths differ markedly for resonances below and above E(n)=300 eV, which is in stark contrast to long-established theory. We show that this change, as well as a similar change in the neutron-width distribution reported previously, is reflected in abrupt increases in both the average (147)Sm(n,γ) cross section and fluctuations about the average near 300 eV. Such effects could have important consequences for applications such as nuclear astrophysics and nuclear criticality safety.

New precision measurements of the 235U(n,γ) cross section.

The neutron capture cross section of (235)U was measured for the neutron incident energy region between 4 eV and 1 MeV at the DANCE facility at the Los Alamos Neutron Science Center with an unprecedented accuracy of 2-3% at 1 keV. The new methodology combined three independent measurements. In the main experiment, a thick actinide sample was used to determine neutron capture and neutron-induced fission rates simultaneously. In the second measurement, a fission tagging detector was used with a thin actinide sample and detailed characteristics of the prompt-fission gamma rays were obtained. In the third measurement, the neutron scattering background was characterized using a sample of (208)Pb. The relative capture cross section was obtained from the experiment with the thick (235)U sample using a ratio method after the subtraction of the fission and neutron scattering backgrounds. Our result indicates errors that are as large as 30% in the 0.5-2.5 keV region, in the current knowledge of neutron capture as embodied in major nuclear data evaluations. Future modifications of these databases using the improved precision data given herein will have significant impacts in neutronics calculations for a variety of nuclear technologies.

Tight control of exogenous SERCA expression is required to obtain acceleration of calcium transients with minimal cytotoxic effects in cardiac myocytes.

Collateral effects of exogenous sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) expression were characterized in neonatal rat and chicken embryo cardiac myocytes, and the conditions required to produce acceleration of Ca(2+) transients with minimal toxicity were established. Cultured myocytes were infected with adenovirus vector carrying the cDNA of wild-type SERCA1, an inactive SERCA1 mutant, or enhanced green fluorescence protein under control of the cytomegalovirus promoter. Controls were exposed to empty virus vector. Each group was tested with and without phenylephrine (PHE) treatment. Under conditions of limited calf-serum exposure, the infected rat myocytes manifested a more rapid increase in size, protein content, and rate of protein synthesis relative to noninfected controls. These changes were not accompanied by reversal to fetal transcriptional pattern (as observed in hypertrophy triggered by PHE) and may be attributable to facilitated exchange with serum factors. SERCA virus titers >5 to 6 plaque-forming units per cell produced overcrowding of ATPase molecules on intracellular membranes, followed by apoptotic death of a significant number of rat but not chicken myocytes. Enhanced green fluorescence protein virus and empty virus also produced cytotoxic effects but at higher titers than SERCA. Expression of exogenous SERCA and enhancement of Ca(2+) transient kinetics could be obtained with minimal cell damage in rat myocytes if the SERCA virus titer were maintained within 1 to 4 plaque-forming units per cell. Expression of endogenous SERCA was unchanged, but expression of exogenous SERCA was higher in myocytes rendered hypertrophic by treatment with PHE than in nontreated controls.

Characterization of new Punch mutations: identification of two additional mutant classes.

The Punch locus of Drosophila melanogaster which encodes the pteridine biosynthetic enzyme, GTP cyclohydrolase, is genetically complex. Lethal alleles of the locus resolve into an array of interallelic complementation groups, and at least one class of mutations is developmentally specific, affecting GTP cyclohydrolase activity only in the heads of adults. All previously isolated Punch alleles were identified on the basis of a mutant eye color phenotype. By screening mutagenized chromosomes over Punch region deficiencies, we have now isolated new alleles on the basis of lethal and visible phenotypes. Most of these alleles fall into previously identified genetic classes, but two new classes of mutations were also found. One class contains two alleles that behave as dominant lethal mutations in some genetic backgrounds. The other class represents a second developmentally specific set of alleles that affect the function of the Punch locus only during embryogenesis.

A genetic analysis of the pteridine biosynthetic enzyme, guanosine triphosphate cyclohydrolase, in Drosophila melanogaster.

Strains with mutant eye color were surveyed for levels of GTP cyclohydrolase (GTP CH), the first enzyme acting in the biosynthesis of pteridines, the pigments causing red eye color in Drosophila. Six strains were found to have reduced GTP CH activity. In five of the six strains, the reduction of activity is apparent only in the adult head of homozygous mutants. We show that mutations in Punch (2-97, Pu) have severe effects on GTP CH activity. In most cases, the reduction of activity is apparent in all tissues and stages that express the enzyme. The activity of GTP CH is shown to be closely correlated with the number of Pu+ genes in the genome. One ethyl methanesulfonate (EMS)-induced Pu mutant has a GTP CH enzyme that is unstable when compared with the wild-type enzyme. Mutations in Pu fall into three general classes. The largest class has a recessive lethal and eye color phenotype, 50% or higher GTP CH activity in heterozygotes, and equivalent defects in all tissues. A second class is dominant in eye color phenotype and recessive lethal, with less than 50% GTP CH activity in heterozygotes. The third class is homozygous viable and has severe reduction of activity in the adult head, but no or less severe loss in other tissues.

Tissue-specific and complex complementation patterns in the Punch locus of Drosophila melanogaster.

Mutations in the Punch locus result in loss of GTP cyclohydrolase activity, but all mutations do not affect the enzyme in the same way. There are at least three classes of Punch mutations. One class results in a dominant eye color, recessive lethal phenotype. A second class of mutations also causes a recessive lethal phenotype, but heterozygous mutants have normal eye color. They show loss of GTP cyclohydrolase function in all tissues where activity can be measured. Alleles comprising a third class are recessive eye color mutations that are homozygous viable. Individuals with this third type of mutation show loss of enzyme activity in the eye, but show normal or near-normal activity elsewhere. In order to examine the organization and function of this locus further, we have performed interallelic complementation tests on 25 Punch mutations, monitoring viability and enzyme activity in prepupae and adults. Most allele combinations are lethal. Those that complement do so in ways that are tissue-or stage-specific and unpredictable. Tests of mutants with tissue-specific phenotypes and of individuals mutant for complementing Punch lethal alleles lead us to conclude that Punch is a complex locus, both with respect to its organization and to its products.

The catecholamines up (Catsup) protein of Drosophila melanogaster functions as a negative regulator of tyrosine hydroxylase activity.

We report the genetic, phenotypic, and biochemical analyses of Catecholamines up (Catsup), a gene that encodes a negative regulator of tyrosine hydroxylase (TH) activity. Mutations within this locus are semidominant lethals of variable penetrance that result in three broad, overlapping effective lethal phases (ELPs), indicating that the Catsup gene product is essential throughout development. Mutants from each ELP exhibit either cuticle defects or catecholamine-related abnormalities, such as melanotic salivary glands or pseudotumors. Additionally, Catsup mutants have significantly elevated TH activity that may arise from a post-translational modification of the enzyme. The hyperactivation of TH in Catsup mutants results in abnormally high levels of catecholamines, which can account for the lethality, visible phenotypes, and female sterility observed in these mutants. We propose that Catsup is a component of a novel system that downregulates TH activity, making Catsup the fourth locus found within the Dopa decarboxylase (Ddc) gene cluster that functions in catecholamine metabolism.

Measurement of Neutron Decay Parameters-The abBA Experiment.

We are developing an experiment to measure the correlations a, A, and B, and the Fierz interference term b in neutron decay, with a precision of approximately 10(-4). The experiment uses an electromagnetic spectrometer in combination with two large-area segmented silicon detectors to detect the proton and electron from the decay in coincidence, with 4π acceptance for both particles. For the neutron-polarization-dependent observables A and B, precision neutron polarimetry is achieved through the combination of a pulsed neutron beam, under construction at the SNS, and a polarized (3)He neutron polarizer. Measuring a and A in the same apparatus provides a redundant determination of λ = gA/gV . Uncertainty in λ dominates the uncertainty of CKM unitarity tests.

Inhibition of cyclic AMP phosphodiesterase (PDE4) reverses memory deficits associated with NMDA receptor antagonism.

Rolipram, a selective inhibitor of type 4 cyclic AMP phosphodiesterase (PDE4), completely reversed the amnesic effects of MK-801 on working and reference memory (F[4,64] = 11.10; p <.0001 and F[4,64] = 2.53; p <.05, respectively) at doses of 0.01-0.1 mg/kg in the radial-arm maze task. Similar antagonism by rolipram of the effects of MK-801 was observed on inhibitory avoidance behavior (F[3,35] = 190.8; p <.0001). In vitro evidence suggests that an increase in cAMP concentrations may mediate the observed behavioral effects of rolipram. In the absence of PDE4 inhibition, NMDA did not increase cAMP concentrations in primary cultures of rat cerebral cortical neurons. However, when PDE4 was inhibited with rolipram, NMDA markedly elevated cAMP. These observations suggest that PDE4 is an integral component of the NMDA receptor-mediated signal transduction pathway involved in memory processes. Inhibitors of PDE4 may act on this pathway to produce their effects on memory and may represent a new class of cognitive enhancers.

Secretion of growth hormone elicited by intravenous desipramine in the conscious, unrestrained rat.

1. Acute intravenous administration of either clonidine (Clon) (50 micrograms kg-1) or desipramine (DMI) (5 mg kg-1) elicited a pulse of growth hormone (GH) and corticosterone secretion in conscious, unrestrained rats. 2. The responses to DMI were similar to those with Clon, except that the GH pulse following DMI was delayed and was not dose-dependent. 3. The GH response to DMI was inhibited by prior administration of idazoxan (1 mg kg-1) or yohimbine (0.5 mg kg-1), but not by atropine (10 micrograms kg-1), sulpiride (5 mg kg-1) or prazosin (1 mg kg-1). 4. The corticosterone secretion following DMI was not altered by prior atropine, sulpiride or prazosin, but was augmented by idazoxan (1 mg kg-1). 5. GH secretion was not influenced by atropine, sulpiride, prazosin or idazoxan given alone. Idazoxan or yohimbine given alone elicited significant secretion of corticosterone. 6. It is concluded that i.v. DMI caused an activation through indirect mechanisms of alpha 2-adrenoceptors specifically involved in hypothalamic-pituitary regulation of GH release and also a distinct, independent and transient generalized activation of the pituitary-adrenal axis.

Neuroendocrine response to clonidine and 8-OH-DPAT in rats following chronic administration of desipramine or sertraline.

1. Rats were administered either desipramine (DMI) or sertraline daily at doses 7.5 mg kg-1 or 10 mg kg-1, i.p., respectively and the effects on the functional state of hypothalamic neuroendocrine control mechanisms assessed by measurements of plasma hormones following acute drug challenge. The effects of treatment on gross behaviour and brain adrenoceptor density were also determined. 2. Both DMI and sertraline caused significant reduction in activity measured as ambulation and rearing at 14 days of treatment. 3. All animals were chronically cannulated after 14 days of treatment and tested for neuroendocrine response to acute i.v. clonidine (50 micrograms kg-1) or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 250 micrograms kg-1) after 21 or more days of treatment. 4. Rats treated with DMI but not sertraline showed a virtually complete suppression of the growth hormone (GH) secretion elicited by clonidine in controls, while the secretion of corticosterone was augmented. 5. Treatment with DMI but not sertraline led to a significantly greater 8-OH-DPAT-induced secretion of prolactin than in the control rats, while the plasma concentrations of corticosterone following 8-OH-DPAT were not influenced by either DMI or sertraline treatment. 6. The density (but not the affinity) of cerebral cortical binding of [3H]-dihydroalprenolol was significantly reduced by DMI treatment. 7. These results show that DMI treatment blunted the sensitivity of post-synaptic alpha 2-adrenoceptors, accompanied by complex interactions manifested as increased responsiveness of alpha 1-adrenoceptors and 5-HT1A receptors. Sertraline had no significant neurendocrine effects at a dose which significantly reduced gross activity.

Effects of chronic administration of amitriptyline or mianserin on rat cardiac and central adrenoceptors.

Rats were administered either amitriptyline (20 mg kg-1, i.p.) or mianserin (10 mg kg-1, i.p.) for 21 consecutive days and the alpha- and beta-adrenoceptor characteristics of cardiac ventricles, cerebral cortex and hippocampus examined by ligand-binding procedure. Chronic administration of amitriptyline significantly reduced the maximum density of beta-receptors in the cerebral cortex without significantly altering cardiac alpha- or beta-receptors; mianserin treatment had no significant effect on any of the receptors studied.

Altered thermoregulatory responses to clonidine in streptozotocin-diabetic rats.

1. The effects of streptozotocin (STZ) treatment on alpha 2-adrenoceptor regulation of body temperature were studied by monitoring the response of colonic temperature to administration of clonidine. 2. A dose-dependent fall in colonic temperature occurred in control rats given clonidine challenge (0.05-2.0 mg kg-1, s.c.); this response was inhibited by prior administration of either yohimbine or idazoxan (2 mg kg-1, s.c.) but not by the peripherally-acting alpha 2-adrenoceptor antagonist L-659,066 (10 mg kg-1, s.c.). 3. In rats treated with STZ (65 mg kg-1, i.v.) administration of clonidine elicited a dose-independent hyperthermia (circa 1 degree C.); this effect was unaltered by prior administration of yohimbine or idazoxan. 4. Naloxone (5 mg kg-1, s.c.) elicited a small fall in temperature (< 1 degree C.) in both control and STZ-treated rats; naloxone pretreatment did not alter the temperature response to clonidine in either group. 5. Nicotinic acid (10 mg kg-1, s.c.) caused a similar small elevation in temperature in both groups. 6. Administration of replacement insulin to STZ-treated rats maintained weight gain and low blood glucose while the thermoregulatory response to clonidine slowly reverted to normal. 7. These results show that altered central temperature control is an element of the generalised abnormality of alpha 2-receptor function induced by STZ.

Phosphorus-31 nuclear magnetic resonance spectroscopy of the spinal cord in the pig, rat, and rabbit.

RATIONALE AND OBJECTIVES: To ensure that contamination-free phosphorus-31 nuclear magnetic resonance (31P-NMR) spectra of the spinal cord could be obtained, a porcine model was adopted that provided a large cord sample and a greater area free from adjacent muscle tissue. METHODS: Phosphorus-31 NMR spectra were acquired from the porcine spinal cord under in vivo conditions using a 4.7-T spectrometer. Spectra also were collected from perchloric acid and lipid extracts, and excised freeze trapped samples of the rat, rabbit, and pig spinal cord. RESULTS: The in vivo spectrum showed resonances corresponding to adenosine triphosphate, phosphocreatine, inorganic phosphate, phosphomonoesterase, and phosphodiesterase as confirmed by extracts. In addition, a broad resonance was observed that was assigned to myelin phospholipids. CONCLUSION: Phosphorus-31 NMR spectra of the spinal cord revealed resonances common to brain tissue. Importantly, the existence of a previously undetected resonance, which is likely to correspond to myelin phospholipids, also is reported. This resonance may prove important in future studies monitoring changes in myelin in response to trauma and ischemia.

Phosphorus-31 magnetic resonance spectroscopy studies of pig spinal cord injury. Myelin changes, intracellular pH, and bioenergetics.

RATIONALE AND OBJECTIVES: Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to monitor changes in phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi), intracellular pH (pHi), and free magnesium in the in vivo pig spinal cord after injury. METHODS: Phosphorus-31 NMR spectra were acquired from healthy (n = 4) and injured pig spinal cords (n = 8) under in vivo conditions using a 4.7-tesla spectrometer. Spinal cords were injured by dropping a 20-g weight from 20 cm onto the surgically exposed cord surface. RESULTS: In vivo spectra of injured cords revealed a reduction in ATP, PCr, pHi, and an increase in Pi. In addition, a broad resonance that is likely to arise from myelin phospholipids was reduced significantly after injury. CONCLUSIONS: Phosphorus-31 NMR can be used to follow in vivo changes in high energy phosphates after injury and may have the potential to follow changes in myelin structure. This technique may prove important in the study of myelin breakdown after secondary, nonreversible spinal cord injury. Changes in high energy phosphates and pHi did not seem to parallel these putative changes in myelin structure.

Differential sensitivity to the effects of albuterol on locomotor activity and operant behavior.

The purpose of the present study was to determine the effects of the beta-2 selective adrenergic agonist albuterol on three behaviors, locomotor activity, behavior maintained under a differential-reinforcement-of-low-rate (DRL) schedule, and behavior maintained under a multiple fixed-interval, fixed-ratio (FI-FR) schedule of reinforcement. Albuterol reduced response rate under the DRL schedule in a manner that resulted in an increase in reinforcement rate. Similarly, albuterol reduced response rate under both components of the multiple FI-FR schedule in a dose-dependent manner. The ED50 values for the effects of albuterol on these two operant behaviors were calculated to be approximately 1 mg/kg and the minimal effective doses were 0.3-1 mg/kg. In addition to affecting operant behavior, albuterol also reduced locomotor activity; the ED50 values and minimal effective doses were 0.05 and 0.03 mg/kg, respectively. The effects of albuterol on DRL behavior, FI-FR behavior and locomotor activity were antagonized by the beta adrenergic antagonist propranolol; this suggests that the behavioral effects of this agonist were mediated, at least in part, by beta adrenergic receptors. The differential sensitivity of locomotor activity and operant behavior to albuterol suggests that the actions of this drug on locomotor activity may be mediated predominantly by peripheral beta adrenergic receptors and that its effects on operant behavior may be mediated by beta adrenergic receptors in the central nervous system.

Effects of the beta-2 adrenergic agonist zinterol on DRL behavior and locomotor activity.

The purpose of the present study was to assess the behavioral effects of the beta adrenergic agonist zinterol and to determine whether its actions were mediated by beta adrenergic receptors. Zinterol reduced response rate and increased reinforcement rate of rats under a differential-reinforcement-of-low-rate schedule in a dose-dependent manner; significant decreases in response rate and increases in reinforcement rate were observed at doses of 0.1-1 mg/kg. The effect of 0.3 mg/kg zinterol on this behavior was blocked by pretreatment with the beta adrenergic antagonist propranolol. Zinterol also reduced locomotor activity in a dose-dependent manner; significant reductions were observed at doses of 0.3-10 mg/kg. Similarly, the effect of 1 mg/kg zinterol on locomotor activity was antagonized by propranolol. These effects of zinterol were similar to those of other beta adrenergic agonists as well as those of antidepressant drugs. Although the site of action (central versus peripheral) of zinterol was not determined in the present study, an experiment was carried out to determine if zinterol could act centrally after peripheral administration. The ability of repeated, systemic administration of zinterol to reduce the density of beta adrenergic receptors in cerebral cortex and cerebellum was determined. Repeated treatment with a high dose of zinterol (10 mg/kg, IP) reduced the density of beta adrenergic receptors in these brain regions, suggesting that, at least under certain conditions, systemically administered zinterol did have access to the central nervous system.