Toward a perceptual theory of flow visualization.

Currently, most researchers in visualization pay very little attention to vision science. The exception is when the effective use of color is the subject. Little research in flow visualization includes a discussion of the related perceptual theory. Nor does it include an evaluation of effectiveness of the display techniques that are generated. This is so, despite Laidlaw's paper showing that such an evaluation is relatively straightforward. Of course, it's not always necessary to relate visualization research to perceptual theory. If the purpose of the research is to increase the efficiency of an algorithm, then the proper test is one of efficiency, not of perceptual validity. But when a new representation of data is the subject of research, addressing how perceptually effective it is - either by means of a straightforward empirical comparison with existing methods or analytically, relating the new mapping to perceptual theory - should be a matter of course. A strong interdisciplinary approach, including the disciplines of perception, design, and computer science will produce better science and better design in that empirically and theoretically validated visual display techniques will result.     

Molecular or pharmacologic perturbation of the link between glucose and lipid metabolism is without effect on glucose-stimulated insulin secretion. A re-evaluation of the long-chain acyl-CoA hypothesis

The mechanism by which glucose stimulates insulin secretion from the pancreatic islets of Langerhans is incompletely understood. It has been suggested that malonyl-CoA plays a regulatory role by inhibiting fatty acid oxidation and promoting accumulation of cytosolic long-chain acyl-CoA (LC-CoA). In the current study, we have re-evaluated this "long-chain acyl-CoA hypothesis" by using molecular and pharmacologic methods to perturb lipid metabolism in INS-1 insulinoma cells or rat islets during glucose stimulation. First, we constructed a recombinant adenovirus containing the cDNA encoding malonyl-CoA decarboxylase (AdCMV-MCD), an enzyme that decarboxylates malonyl-CoA to acetyl-CoA. INS-1 cells treated with AdCMV-MCD had dramatically lowered intracellular malonyl CoA levels compared with AdCMV-betaGal-treated cells at both 3 and 20 mM glucose. Further, at 20 mM glucose, AdCMV-MCD-treated cells were less effective at suppressing [1-14C]palmitate oxidation and incorporated 43% less labeled palmitate and 50% less labeled glucose into cellular lipids than either AdCMV-betaGAL-treated or untreated INS-1 cells. Despite the large metabolic changes caused by expression of MCD, insulin secretion in response to glucose was unaltered relative to controls. The alternative, pharmacologic approach for perturbing lipid metabolism was to use triacsin C to inhibit long-chain acyl-CoA synthetase. This agent caused potent attenuation of palmitate oxidation and glucose or palmitate incorporation into cellular lipids and also caused a 47% decrease in total LC-CoA. Despite this, the drug had no effect on glucose-stimulated insulin secretion in islets or INS-1 cells. We conclude that significant disruption of the link between glucose and lipid metabolism does not impair glucose-stimulated insulin secretion in pancreatic islets or INS-1 cells.     

Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography

BACKGROUND: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I] beta-CIT SPECT and platelet [3H]paroxetine binding. METHODS: Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-CIT and imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3" = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons. RESULTS: Results showed a statistically significant reduction in brainstem V3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I] beta-CIT binding (r = -0.14, p = .48). CONCLUSIONS: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.     

Estrogen-induced alteration of mu-opioid receptor immunoreactivity in the medial preoptic nucleus and medial amygdala

The mu-opioid receptor (mu-OR), like most G-protein-coupled receptors, is rapidly internalized after agonist binding. Although opioid peptides induce internalization in vivo, there are no studies that demonstrate mu-OR internalization in response to natural stimuli. In this study, we used laser-scanning microscopy to demonstrate that estrogen treatment induces the translocation of mu-OR immunoreactivity (mu-ORi) from the membrane to an internal location in steroid-sensitive cell groups of the limbic system and hypothalamus. Estrogen-induced internalization was prevented by the opioid antagonist naltrexone, suggesting that translocation was largely dependent on release of endogenous agonists. Estrogen treatment also altered the pattern of mu-ORi at the bright-field light microscopic level. In the absence of stimulation, the majority of immunoreactivity is diffuse, with few definable mu-OR+ cell bodies or processes. After stimulation, the density of distinct processes filled with mu-ORi was significantly increased. We interpreted the increase in the number of mu-OR+ processes as indicating increased levels of internalization. Using this increase in the density of mu-OR+ fibers, we showed that treatment of ovariectomized rats with estradiol benzoate induced a rapid and reversible increase in the number of fibers. Significant internalization was noted within 30 min and lasted for >24 hr after estrogen treatment in the medial preoptic nucleus, the principal part of the bed nucleus, and the posterodorsal medial amygdala. Naltrexone prevented the increase of mu-OR+ processes. These data imply that estrogen treatment stimulates the release of endogenous opioids that activate mu-OR in the limbic system and hypothalamus providing a "neurochemical signature" of steroid activation of these circuits.     

Further studies on the influence of genotype and dietary protein on the performance of broilers

An experiment was conducted to quantify genetic differences in response to dietary protein level of male vs female broilers. Broilers (1 d old) from a "high-yield" strain cross (Ross x Ross 208) and a "fast-growing" strain cross (Peterson x Arbor Acres) were placed on fresh pine shavings in floor pens. From Day 0 to 18, all birds were fed a 23% CP starter diet. During Days 18 to 53 male birds were fed either a 16, 18, 20, 22, 24, or 26% CP diet (3,200 kcal ME/kg) and female birds were fed the 16, 20, or 24% CP diet. Significant differences (P < 0.05) were noted in the performance of the different strains. Ross x Ross 208 male birds had a higher body weight (3.37 vs 3.16 kg), higher feed intake (7.08 vs 6.78 kg), higher breast yield (31.76 vs 29.25%), higher carcass yield (73.90 vs 71.85%), and a lower adjusted feed conversion ratio (FCR; 2.10 vs 2.16 g:g) than Peterson x Arbor Acres males at 53 d of age. As compared to Peterson x Arbor Acres females, Ross x Ross 208 female broilers also had a higher body weight (2.68 vs 2.55 kg), higher breast meat yield (33.61 vs 30.80%), higher carcass yield (75.31 vs 73.91%), and lower adjusted FCR (1.97 vs 2.04 g:g). Qualitative differences in the response of these strains were confirmed and better qualitative data is presented that can be used to predict the important output parameters from the import inputs in broiler production.     

Healing of adult male survivors of childhood sexual abuse

1. Lamotrigine is a new antiepileptic drug, chemically unrelated to currently used antiepileptic medication. Its pharmacokinetics can be influenced by concomitant antiepileptic medication. 2. This study was performed to assess the pharmacokinetic profile of lamotrigine in three groups of children treated with different types of comedication: drugs known to induce, to inhibit or to have no clinically significant influence on drug metabolism, respectively. 3. Thirty-one children aged 6 months to 5 years were included and received a 2 mg kg-1 single oral dose. Lamotrigine plasma profiles were different between the three comedication groups. The half-lives (mean +/- s.d.) were: 7.7 +/- 1.8 h, 21.9 +/- 6.8 h, 44.7 +/- 10.2 h in the "inducer', "other' and "inhibitor' groups respectively. 4. Patients were then dosed to steady state, with the dosage adjusted on the basis of the single dose pharmacokinetics to achieve a minimum plasma concentration between 1.5 and 3 mg l-1. The mean minimum plasma concentration for the three groups was 2.54 +/- 1.28 mg l-1 at steady state. 5. Dosage of lamotrigine can be optimised with knowledge of the metabolic effects of antiepileptic comedication.     

Signal transduction in vertebrate growth cones navigating in vivo

Navigating growth cones need signal transduction machinery to amplify and transmit the effects of extracellular signals throughout the growth cone. In culture, many drugs that affect second messengers are known to modulate neurite extension (with different effects on different neurons), and gradients of calcium influx and cyclic nucleotide analogs can cause growth cones to turn. However, it is not clear which of these responses are physiologically relevant, as axons grow through much more complex environments in vivo. The "exposed brain" preparation in Xenopus embryos provides an experimentally tractable system in which it is possible to study growth, pathfinding, and target recognition of retinal growth cones in vivo, while pharmacologically manipulating their signal transduction systems. These growth cones can also be easily studied in explant culture. We describe preliminary results of parallel in vivo and in vitro experiments using an array of drugs that perturb transduction molecules. Surprisingly, calcium ionophores and cyclic nucleotide analogs have no significant effect on retinal axon growth or pathfinding. Several agents including herbimycin A, ML-7, mastoparan, and RHC80267 inhibit retinal axon growth, both in vivo and in vitro, suggesting that tyrosine kinases, myosin, heterotrimeric G-proteins, and diacylglycerol lipase are important for retinal growth cones navigating in the optic pathway.     

Spontaneous output of acetylcholine from rat diaphragm preparations declines after treatment with botulinum toxin

A gas chromatographic spectrometric assay was used to measure tissue and released acetylcholine and choline in diaphragm preparations of rats previously injected with botulinum toxin type A. Botulinum intoxication was found not to alter the acetylcholine content of rat diaphragms in vivo or in fully paralyzed muscles in vitro. This result provides direct support for the hypothesis that botulinum toxin blocks transmitter release without affecting acetylcholine synthesis. However, in diaphragm preparations in vitro, this toxin was found to inhibit not only the evoked release of acetylcholine but also the spontaneous "leakage" of acetylcholine that is measured at rest. Additional experiments were performed to characterize this action of the toxin. The magnitude of the decline in resting acetylcholine output appears to be too large to be accounted for solely by the known effect of botulinum toxin to reduce the frequency of miniature endplate potentials. The mechanism of this action of botulinum toxin remains an enigma.     

Conflict-preserving abstraction of discrete event systems using annotated automata

This paper proposes to enhance compositional verification of the nonblocking property of discrete event systems by introducing annotated automata. Annotations store nondeterministic branching information, which would otherwise be stored in extra states and transitions. This succinct representation makes it easier to simplify automata and enables new efficient means of abstraction, reducing the size of automata to be composed and thus the size of the synchronous product state space encountered in verification. The abstractions proposed are of polynomial complexity, and they have been successfully applied to model check the nonblocking property of the same set of large-scale industrial examples as used in related work.     

Dream patterns in Anglo and Chicano young adults

This study is the conclusion of an exploratory cross-cultural investigation of dream content and organization. Following our report in "Ego Modalities in the Manifest Dreams of Male and Female Chicanos," (Brenneis and Roll, 1975), this paper examines differences in the organization and content of dreams: (1) between Anglo men and women; (2) between Anglo and Chicano men and Anglo and Chicano women; and (3) between Anglos and Chicanos.