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Publisher Summary This chapter presents computation of viscous compressible flow using boundary-fitted coordinate systems and the application of this computational philosophy on a vector computer. Viscous-compressible aerodynamic simulation is the numerical solution of the compressible Navier-Stokes equations and associated boundary conditions. An algebraic approach to boundary-fitted coordinate systems is one where an explicit functional relation describes a mesh on which a solution is obtained. This approach has the advantage of rapid-precise mesh control. The basic mathematical structure of three algebraic mesh generation techniques is described. They are transfinite interpolation, the multi-surface method, and the two-boundary technique. The Navier-Stokes equations are transformed to a computational coordinate system where boundary-fitted coordinates can be applied. Large-scale computation implies that there is a large number of mesh points in the coordinate system. Now a transformation between the physical domain and the computational domain is a mathematical relationship mapping one domain into the other. Similarly the mesh in one domain is mapped into the mesh in the other domain. When the transformation maps boundaries in the physical domain into boundaries in the computational domain, the term “boundary-fitted coordinate system” is used to describe the transformation.

Plasma ketamine concentrations after diazepam and placebo pretreatment were examined in a double-blind, randomized, cross-over study. Eight healthy male subjects received either diazepam or a 0.9% NaCl placebo before ketamine and received the alternate combination 5 to 24 days later. Ten minutes before ketamine dosing, diazepam, 0.3 mg/kg, or placebo in equal volume was injected intravenously at a rate not exceeding 5 mg/min. Ketamine, 2.2 mg/kg iv, was injected over 1 min. For the clinically relevant period for anesthesia (1 to 30 min), diazepam-ketamine treatment resulted in higher plasma levels at most time points, but diazepam pretreatment did not alter plasma levels of metabolite KI and pseudometabolite KII nor the 24-hr urinary excretion of ketamine, KI, and KII. Ketamine kinetics followed a three-term exponential decline under both treatment conditions. After placebo-ketamine dosing, plasma t 1/2s were as follows: distribution (pi t 1/2) = 24.1 sec, redistribution (alpha t 1/2) = 4.68 min, and elimination (beta t 1/2) = 2.17 hr. After diazepam-ketamine dosing, t 1/2s were: pi t 1/2 = 25.0 sec, alpha t 1/2 6.37 min, and beta t 1/2 = 2.32 hr.

These experiments were performed in order to ascertain whether activation of coronary vascular adrenergic receptors could change the time course of the coronary vasodilatation accompanying increases in myocardial metabolic activity. The left common coronary arteries of dog hearts were perfused in situ with blood at constant flow. Coronary perfusion pressure and coronary sinus blood 02 content were continuously monitored. Norepinephrine was infused into the coronary artery at 0.5 to 5 microgram.min-1. and isoprenaline at 0.5 to 2 microgram.min-1. The amplitude of the vascular resistance change was less with norepinephrine than with isoprenaline infusion for a similar change in oxygen consumption. The time course of coronary vascular resistance, after correction for the effects of vascular transit, lagged significantly behind the time course of coronary sinus 02 content in the case of norepinephrine infusion. On the average, no lag was observed with isoprenaline infusion. It is concluded that stimulation of coronary vascular adrenergic receptors can alter the time course and the magnitude of the coronary vascular response to increases in myocardial metabolic activity resulting from myocardial beta-receptor stimulation.

Ion chromatography has been applied to the simultaneous, multi-component determination of biologically important anions. More than 20 different biologically important anions were separated on high performance ion-exchange columns and detected using chemically suppressed conductivity. Application of the technique to the separation of inositol mono-, bis-, and trisphosphates shows that these compounds can be separated from the other ions tested and can be detected at concentrations that may be found in vivo. For inositol monophosphate, the conductivity was proportional to the amount of compound from less than 20 pmol to more than 400 nmol. Although alternative methods are available for assaying each of these anions individually, the advantages of ion chromatography lie in the sensitivity of detection, the speed of separation, and the ability to simultaneously determine numerous ions. This method should be broadly applicable to studies of second messengers, measurements of reaction rates, and various metabolic studies.

SynopsisTardive dyskinesia is widely believed to be a state of relative hyperdopaminergic and hypocholinergic imbalance in the striatum of patients chronically treated with neuroleptics. However, not all patients with tardive dyskinesia respond to cholinergic drugs, which theoretically should restore the balance and improve the symptoms. We report a controlled, double-blind, crossover study of choline chloride in 11 patients with persistent tardive dyskinesia. Seven patients showed partial or minimal improvement, while two did not change and two deteriorated. The results are discussed in the light of other similar findings in the literature, and the implications for pharmacological subtypes of tardive dyskinesia using cholinergic probes are explored.

Under optimal conditions, CPV transcription in vitro was maintained for more than 24 hr, resulting in large quantities of full-size mRNAs. The mRNAs were resolved into nine discrete bands by agarose gel electrophoresis in the presence of 7 M urea. The genome dsRNA segments coding for each mRNA were identified by hybridizing the separated, 32P-labeled mRNA to a mixture of genome RNAs. Each of the genome segments appears to be transcribed at the same rate, producing equal quantities by weight but different molar amounts of the separated individual mRNA species. These results imply that each of the genome segments is transcribed repeatedly by an equal number of template-associated RNA polymerases at the same rate of chain elongation. The genome RNAs of CPV and reovirus, labeled at the 3′-termini with 32pCp by RNA ligase, were separated by agarose gel electrophoresis into the plus and minus strands. The RNA strands of plus polarity were found to migrate faster in the gel than those of minus polarity for all CPV dsRNA genome segments, whereas the opposite was seen for most of the reovirus genome segments. The basis of this separation is due to retention of secondary structure during the electrophoresis even in the presence of 7 M urea.

Problems that emerged during the development of the natural environment definitions for the design of the National Aerospace Plane (NASP) are discussed. The NASP program objectives are reviewed. It is found that some of the data needed to determine the environmental parameters for designing the aircraft are unavailable. It is suggested that this is due to a lack of technology for making the necessary measurements.

Activity of the acyl-CoA hydrolase in liver microsomes was found to be inhibited by 1-acyl- sn -glycerophospholipids in a concentration dependent manner ranging from 5–50 μM. Inhibition occurred at all acyl-CoA concentrations tested, although the inhibitory effect was higher with low concentrations of acyl-CoA. It is evident that in the cellular system where acyl-CoA is normally maintained at a low level, the inhibition of acyl-CoA hydrolysis by lysophospholipids would facilitate acyl-CoA transfer to the lyso-phospholipids. This phenomena may be important in regulating the metabolism of acyl-CoA and lyso-phosphoglycerides since an accumulation of either type of the compounds may cause potentially deleterious effects to the cell membrane functions.

A study was conducted to assess the feasibility of substituting diazepam for pentobarbital and phenobarbital in sedative-hypnotic tolerance testing and withdrawal of tolerant patients. Nineteen patients potentially dependent on sedative-hypnotics were tolerance tested with either diazepam or pentobarbital and, if tolerant, were withdrawn with diazepam or phenobarbital, respectively. Seventy-eight subjects previously described in the literature with drug dependencies similar to the diazepam and barbiturate groups provided a basis for comparing the diazepam group to untreated patients to determine whether diazepam was able to prevent abstinence symptoms. Withdrawal was successfully completed in all patients. The expected and observed incidence of seizures, delirium, and minor withdrawal for the barbiturate group and seizures and delirium for the diazepam group did not differ significantly, although a large type II error compromised these conclusions. A significant difference was seen between the observed and expected incidence of minor withdrawal symptoms in the diazepam-withdrawn patients.

Until recently the use of synthetic peptides in protease research was rather limited; this was mainly due to the lack of suitable substrates and effective reaction principles (Pearse, 1972; Smith and van Frank, 1975; Lojda et al., 1979). However, especially during the last years substantial progress was achieved in this field; it is the aim of the present report to describe the most important advances in the use of synthetic peptide substrates.

This paper describes a low-resolution system for identifying variant hemoglobins with great sensitivity and specificity. After electrophoresis of the hemoglobin sample in a gel, fixation is used to entrap the hemoglobin. The gel is dried, incubated with a monoclonal antibody against the desired hemoglobin, then incubated with a second antibody against the first antibody which is conjugated with the enzyme beta-d-galactosidase. An enzyme overlay membrane containing a fluorogenic substrate is then placed on the gel surface, incubated, and removed, yielding an immunofluorescent print. The entire procedure takes only two hours, and by virtue of fluorescent detection gives sharper band resolution and greater sensitivity than conventional dye methods. The system clearly distinguishes SS sickle-cell hemoglobin from heterozygous and "S-like" hemoglobins. The technique therefore holds promise as a powerful probe for allelic variants.

Glycerol-3-phosphate dehydrogenase (EC 1.1.1.8) from rabbit skeletal muscle is inhibited by pyridoxal-5′-phosphate. The inhibition observed in steady-state kinetic studies is competitive with respect to dihydroxyacetone phosphate and uncompetitive with respect to NADH. Similar inhibition was found for a series of related compounds which in order of increasing effectiveness of inhibition were: 4-deoxypyridoxine

In the computation of flow fields about complex configurations, it is very difficult to construct body-fitted coordinate systems. An alternative approach is to use several grids at once, each of which is generated independently. This procedure is called the 'multiple grids' or 'zonal grids' approach and its applications are investigated in this study. The method follows the conservative approach and provides conservation of fluxes at grid interfaces. The Euler equations are solved numerically on such grids for various configurations. The numerical scheme used is the finite-volume technique with a three-stage Runge-Kutta time integration. The code is vectorized and programmed to run on the CDC VPS-32 computer. Some steady state solutions of the Euler equations are presented and discussed.

In an attempt to determine the role of serotoninergic mechanisms in the pathophysiology of tardive dyskinesia, the serotonin precursor 5-hydroxytryptophan (5HTP) with carbidopa, a peripheral decarboxylase inhibitor, were given in a double-blind crossover design to seven patients with longstanding tardive dyskinesia. In the five patients who completed the study, there was no change in dyskinetic movements. Most of the patients had worsening of psychotic symptoms with 5HTP. The data suggest that serotonin precursors have no therapeutic effects in tardive dyskinesia. The implications for the role of serotonin in the pathophysiology of tardive dyskinesia are discussed.

The use of synthetic peptides in biochemical and histochemical assays has considerably contributed to the progress in protease research and therefore to our knowledge about proteases in healthy and diseased cells and tissues (cf. Huseby and Smith, 1980, Gossrau, 1981; Lojda, 1981; Gossrau et al., this volume).

Ion chromatography is shown to be capable of simultaneous determination of biologically important anions. Application of this technique is illustrated for the separation and quantification of the major anions present in rat brain and liver tissues. Sugar phosphates and carboxylic acids are separated on high-performance anion-exchange columns and are detected using chemically suppressed conductivity. Detection limits range from 20 to 100 pmol for the anions tested, including inositol phosphates, lactate, pyruvate, glucuronic acid-1-phosphate, fructose-6-phosphate and glucose-6-phosphate. The coefficient of variation for the determination of most anions was in the range 5–10%. Many of these anions are either difficult to separate with other methods, or require expensive radiochemical techniques for detection. This method should be applicable to other biological studies, from the flow of carbons in photosynthesis to the study of synaptic transmission.

Anion chromatography methods have been developed to determine the concentrations of inositol phosphates and other water-soluble metabolites in rat brain. The cerebral cortex, hippocampus, and striatum were analyzed by chemically suppressed conductivity detection. Animals were sacrificed by directed microwave irradiation for more accurate estimations of in vivo concentrations. The effects of different sample preparation methods are compared. Trichloroacetic acid, formic acid, and perchloric acid extraction result in lower recoveries of phosphocreatine and other anions than does homogenization with water followed by chloroform-methanol extraction. The effects of postdecapitative ischemia on metabolite concentrations are determined. These methods will be used to study the effects of pharmacological agents on inositol phosphates and should be broadly applicable to the analysis of a variety of biological systems.

The effect of steady state therapeutic theophylline serum levels on lithium clearance was investigated. A significant increase in lithium clearance occurred with the administration of theophylline. Despite considerable intersubject variability, a direct lithium clearance estimation method demonstrated a mean increase of 30% with the addition of theophylline. The concomitant use of lithium and theophylline potentially may alter lithium levels sufficiently to result in manic or depressive relapses in patients receiving lithium prophylactically.

Glycerol-3-phosphate dehydrogenase (sn-glycerol-3-phosphate:NAD+ 2-oxido-reductase, EC 1.1.1.8) has been shown to be sensitive to inhibition by iodoacetate. The reaction of the enzyme with iodoacetate, which appears to be a simple bimolecular process, is accompanied by a corresponding loss of enzyme activity. In addition to changes in activity, the alkylation reaction was monitored by the incorporation of radioactivity from iodo[2-14C]acetate, by changes in amino acid composition, and by changes in the content of free sulfhydryl groups. It is concluded that there are two cysteine residues in the native dimeric enzyme which are essential for enzymic activity. The rate of inactivation was relatively insensitive to the presence of various compounds with the exception of NADH which markedly inhibited the reaction. Kinetic and binding studies showed that the binding of NADH prevents alkylation and, conversely, alkylation prevents NADH binding. From the pH dependence of the alkylation reaction, the pKa of the essential sulfhydryl groups was calculated to be 8.5 and it is suggested that the binding of coenzyme is independent of the state of ionization of these groups.

Publisher Summary This chapter discusses the environmental control of manned space vehicles. Essential to the planning for man in space is the recognition that man is of terrestrial origin and that in the general ecology of man lie important sequelae of his earth-born extraction and gregarious habits. Thus, a man reflects in structure and behavior a basic relationship to the polarizing forces of gravity and the periodicities and intensities of sidereal, solar, and lunar events. A major aspect of man's leap into space may reduce to the problem of a design of his microcosm so as to include the simulation of sensory inputs essential to his physical orientation and retention of identification with his earthly self. Apart from energy balance, the prime factors for this may well be simply those of human companionship and, as a likely speculation, an imposed orientational vector simulating that of gravity. Besides atmosphere, food, and varying degrees of reduction and recycling of the products of metabolism, the space vehicle and its biological payload must achieve a balanced energy state compatible with life support with respect to heat storage and quantum exchange.

A double-blind repository emulsion study for mountain cedar pollinosis was accomplished during the pollen season of 1962–1963. The active emulsion contained 1000 protein nitrogen units of pollen extract. Thirty-four patients participated in the study, and only 6 had not received prior therapy. The group that received the active emulsion had a better mean score than the placebo group, but the difference was not statistically significant. The previous aqueous or emulsion therapy may have contributed to the apparent benefit from the placebo treatment.

The worldwide distribution of Air Force personnel, with exposure to various regional pollens, climatic conditions, and other stressful physical conditions, influences the course and pattern of allergic diseases. The detection of allergy at the recruiting level has caused the disqualification of applicants. Whereas in the past the primary symptom in recruits, as seen in 1944, was asthma, now the screening processes has helped to eliminate this. It is evident that the incidence of rhinitis and other upper respiratory tract diseases has increased. This group of diseases, rhinitis, and sinusitis need more observation and scrutiny. As a result of this study, it becomes obvious that there is a definite need for training more physicians in the field of allergy in the Air Force to solve these problems.

Liver mitochondrial systems of varying heterogeneity with respect to microsomal-soluble components were isolated from thyroidectomized and normal rats given l-thyroxine at various dose levels (0, 3, 10, 30, 100, 500 and > 500 µg daily) for 14 days. Degree of homogeneity of fractions was checked by electron and light microscopy. Determinations were made as functions of fraction and thyroxine dose on respiration, phosphorylation, TPNH- and DPNH-cytochrome c reductase activities, DPN content and optical densities. With well washed, homogeneous mitochondrial preparations, stimulation of respiration was obtained without concurrent reduction in P/O ratios, whereas in the more heterogeneous fractions, the qO2OO2 was not elevated, and P/O ratios decreased with increasing dose levels. DPNH- and TPNH-cytochrome c reductase levels were respectively decreased and increased with increasing hormone dosages; the extent of mitochondrial swelling increased, and the DPN content of the mitochondria decreased with dose. The striking change effected by thyroxine on the cytochrome c reductases is at variance with current theory on the regulatory role assigned to the TPNH-DPNH shunt in this respect. Results indicate that thyroxine controls respiration in the mitochondrion directly but that this agent may exert its effects on the phosphorylating activities of the cell by action primarily at some extramitochondrial site.

Electron microscopic subcellular changes of acid hydrolases were studied in the human endometrium during the individual phases of the menstrual cycle. Acid phosphatase (Ac Pase) was identified at the electron microscopic level as the “marker enzyme” of acid hydrolase activity. The proliferative phase is characterized by development of the Golgi systems and lysosomes. The Golgi system becomes progressively more complex; it contains increasing amounts of Ac Pase reaction product, and with the release of more vesicles, the number of lysosomes continuously increases. After ovulation these changes become even more expressed, and during the mid secretory phase the Golgi complexes are developed to their greatest degree. The most dynamic enzymorphologic changes occur during the late secretory phase and early menstrual bleeding. They are characterized by increase of Ac Pase staining within the intercellular spaces of the stromal and epithelial layer; gradual penetration of Ac Pase into junctional complexes of the ...

It is shown that the equation of inert gas uptake by a distinct parallel tissue-blood arrangement coincides, under certain conditions, with two formulations which neglect the possible existence of a blood-tissue barrier. The first of these approximations is the classic von Schrotter equation in continuous form, whereas the second is the empirical one frequently used by contemporary authors. The condition for coincidence is that the product of permeability and blood-tissue exchange surface greatly exceed the rate of blood flow to the tissue. It is difficult to examine this condition at present because of a dearth of gas permeability measurement and because apparently there exist no measurements of surface and flow on the same tissue. A compilation is made of such values as are available, and it is found that on the assumption that gas permeabilities are of the order of 1×10−3 cm sec−1, the conditions for neglecting the blood-tissue barrier may be met in many cases and certainly not met in many others. It is concluded that under these circumstances the more exact equations, taking into account the barrier, should be employed, at least until precise independent measurements justifying the approximations become available.

Interactions between production wells through thick permafrost are considered in general terms. These interactions include thaw and freeze-back, subsidence and heave, and compressive and tensile forces caused by relative movement between soil and well casing. Magnitudes of these interactions are predicted for permafrost and well conditions found in the Prudhoe Bay oil field. There are various design possibilities. End_of_Article - Last_Page 2505

In young adult laboratory rats exposed to cold (6°C) the brown adipose tissue undergoes time-dependent increases in cellularity, vascular supply, and total mass. These changes are largely complete after 16 days in the cold and concurrent generally with the development of a thermoregulatory state not greatly dependent upon shivering. Histologically the brown fat changes from a tissue having both unilocular and multilocular fat cell types to one having almost exclusively the latter. During the first 6 to 12 hours in cold, the multilocular cells lose their lipid vacuoles and decrease in size, but these features are restored to normal by 24 hours. Cell proliferation, as estimated by the DNA synthetic index method (using tritiated thymidine autoradiography), appears in the reticuloendothelial cells of the brown fat at 1 day of cold exposure, becomes maximal at 4 days, and returns to the control level by 16 days. In animals injected with tritiated thymidine on the 3rd day of cold exposure and then maintained for 1 or more additional days in the cold, autoradiographs indicate that new brown fat (multilocular) cells arise by cytogenesis from reticuloendothelial progenitor cells and not by proliferation of existing brown fat cells. Throughout this and subsequent periods, cells of the epididymal white adipose tissue slowly decrease in size. Because a thermogenic role in cold acclimation has been established for the brown fat, the reported changes are regarded as adaptive responses to a cold environment.

Increasing interest in elucidating the role of the lysosome in intracellular metabolic economy has resulted in a deeper understanding of some inborn errors of metabolism, as well as a clea...

The effects of temperature in vitro upon metabolic rates of homogenates of brown fat and liver from control and cold-acclimated rats have been examined over the range 10–37 °C. At all temperatures, brown adipose tissue exhibits a higher rate of oxygen consumption [Formula: see text] than does liver, α-ketoglutarate being used as substrate. At 10 °C, brown adipose tissue retains a larger percentage (36–38%) of its 37 °C metabolic rate than does liver (22–24%).Q10 values and energies of activation (Ea) have been determined and compared with other data reported for these tissues. At 20 °C, breaks appear in the Arrhenius plots for liver from both control and cold-acclimated rats and also for brown fat from control rats, but not for the brown fat from cold-acclimated rats. Thus brown adipose tissue from cold-acclimated rats retains relatively higher levels of respiration at temperatures below the 20 °C breaking point than does brown fat from control rats.In view of previously reported cold-induced increases in mass, vascularity, and [Formula: see text] of brown fat, this decreased temperature sensitivity in the cold-acclimated rats appears wholly consonant with the adaptive behavior of brown fat in its role as a thermogenic effector.

The effect of bipedal stance on the breaking stress in compression of rat femora is investigated as a function of animal weight. It is shown that the breaking stress is a linear function of body weight, bone density and specific calcium content of the femur. In all cases investigated, bipedal femora are shown to have a higher breaking stress than controls. It is concluded that there is a continuous change in the quality as well as the quantity of bone in the rat femur with age and that the increased strength of bone material found in bipedal animals compared to controls as well as large animals as compared to small ones, cannot be explained on the basis of bone mineral content alone.

Multi-agent software systems can be modeled as complex, dynamic systems in which agent adaptation and interaction occur continuously and concurrently. A genetics inspired view has agent adaptation occurring via the exchange of encoded agent characteristics (genes). An economics inspired view has agent adaptation driven by changes in prices and supply and demand. Interactions of economics and genetics models have a long history in evolutionary computation. This paper describes new work towards a synergistic combination of these views, in agent-based settings. The paper includes a re-statement of Holland's (1992) basic theories in an agent-based context, a discussion of different self-organization principles taken from economics, presentation of results from two agent systems that synergize economics and genetics models, and a discussion of future directions.

One highly verbal S was interviewed via a standardized videotaped presentation of E followed later by a live E reading the same library of utterances from a script to S in a face-to-face encounter. The temporal data of the two interview techniques are quite similar.

FOB some time1,2 it has been realized that thyroid hormone raises metabolic rates, nincreases activity of the hexose monophosphate pathway, decreases apparent TPNH–DPN transhydrogenase activity and stimulates 5 α-steroid reductase activity. More recently thyroxin has been shown to increase by a factor of ten or twenty the activity of the intra-mitochondrial α-glycerophosphate dehydrogenase with no concurrent effect on the ‘soluble’ counterpart3,4.