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Carbon - the first frontier of information processing.

Information is often encoded as an aperiodic chain of building blocks. Modern digital computers use bits as the building blocks, but in general the choice of building blocks depends on the nature of the information to be encoded. What are the optimal building blocks to encode structural information? This can be analysed by substituting the operations of addition and multiplication of conventional arithmetic with translation and rotation. It is argued that at the molecular level, the best component for encoding discretized structural information is carbon. Living organisms discovered this billions of years ago, and used carbon as the back-bone for constructing proteins that function according to their structure. Structural analysis of polypeptide chains shows that an efficient and versatile structural language of 20 building blocks is needed to implement all the tasks carried out by proteins. Properties of amino acids indicate that the present triplet genetic code was preceded by a more primitive one, coding for 10 amino acids using two nucleotide bases.

Amino Acid Sequence↗

Kinetics of sodium in rabbit arterial wall: inability of aldosterone to alter extra to intracellular distribution.

Transport rate constants (kij) describing the kinetics of Na exchanges in isolated rabbit aorta wall were determined by a previously established method involving the use of 22Na as a tracer and digital computer simulation without recourse to ancillary chemical measurements of extracellular space. A three compartment model consisting of (i) extracellular, (ii) intracellular and (iii) subcellular spaces (compartments) was found to describe adequately the kinetics of 22Na. Normative values for intercompartmental kij and extra to intracellular Na ratio were established. It appears that the Na extracellular space in rabbit arterial wall is larger than that in dog or rat arterial wall. Surprisingly, at variance with several tissues of different species (dog, rat, mouse and human tissues), aldosterone did not influence the extra to intracellular distribution of Na. The findings are interpreted in the light of results obtained previously by other workers using entirely unrelated methodologies and suggest that species difference is an important factor to consider when studying effects of aldosterone on tissue electrolyte distribution in the rabbit.

Aldosterone↗

Dynamic simulation of electromechanical systems: from Maxwell's theory to common-rail diesel injection.

This paper describes the state-of-the-art of dynamic simulation of electromechanical systems. Electromechanical systems can be split into electromagnetic and mechanical subsystems, which are described by Maxwell's equations and by Newton's law, respectively. Since such systems contain moving parts, the concepts of Lorentz and Galilean relativity are briefly addressed. The laws of physics are formulated in terms of (partial) differential equations. Numerical methods ultimately aim at linear systems of equations, which can be solved efficiently on digital computers. The various discretization methods for performing this task are discussed. Special emphasis is placed on domain decomposition as a framework for the coupling of different numerical methods such as the finite element method and the boundary element method. The paper concludes with descriptions of some applications of industrial relevance: a high performance injection valve and an electromechanical relay.

Journal Article↗

Influence of technetium-99m-hexamethylpropylene amine oxime injection time on single-photon emission tomography perfusion changes in epilepsy.

By digitally computing perfusion changes from ictal or postictal (peri-ictal) injections referenced to those acquired interictally, an enhanced method for localizing the epileptogenic area is reported. Computer-based image processing methods for quantifying regional percent change in the brain are applied to a group of 19 epilepsy patients after the injection of technetium-99m hexamethylpropylene amine oxime (HMPAO) and after acquiring single-photon emission tomography (SPET) data. Each patient's region of epileptogenesis was independently localized through pathology and/or successful surgery. The positive and negative quantitative perfusion changes were plotted as a function of the time of the 99mTc-HMPAO ictal injection. This time scale was normalized relative to the seizure duration and is referenced to the time of seizure termination. Eight patients, injected ictally, demonstrated perfusion increases of 25%-100% in the area of known epileptogenesis. Five patients, injected immediately after seizure cessation, demonstrated excessive perfusion decreases of 30%-92% associated with the region of seizure onset. Six patients, injected well after seizure termination, demonstrated hypoperfusion changes less than 30% at the epileptogenic area. Observations on perfusion changes calculated from 99mTc-HMPAO SPET scans, as a function of normalized time, support a progression from ictal hyper- to excessive hypo-, then finally to persistent interictal hypoperfusion. By applying this perfusion pattern model and by noting the time of injection for peri-ictal images, an improved method for localizing the epileptogenic area is demonstrated.

Adult↗

Use of the calibrated carotid pulse tracing for calculation of left ventricular pressure and wall stress throughout ejection.

Calibrated carotid pulse tracings have been found previously to provide accurate estimates of end-systolic pressure. This study extends this technique to the estimation of arterial pressure throughout ejection. In twenty patients without aortic stenosis (age range 8 to 67 years), simultaneous recordings were made of the pressure tracing in the ascending aorta, externally recorded carotid pulse tracing, phonocardiogram, left ventricular echocardiogram, and peripheral blood pressure. Data were computer digitized and plots of arterial pressure were derived from the aortic pressure tracing (PA) and from the carotid pulse tracing (Pc). Left ventricular (LV) wall stress was then calculated throughout ejection using PA or Pc. The noninvasive estimation of pressure was excellent, with a maximum difference of 3.4 mm Hg between population means. This occurred within the first third of ejection. The wall stress calculations were similar, with a maximum mean population error of 3.5 gm/cm2 at 20% of ejection. The peak wall stress values had a mean difference of 1.4 gm/cm2; mean wall stress over the LV ejection period was 0.5 gm/cm2 higher when calculated from Pc than from PA. Thus, the carotid pulse tracing provides an accurate reproduction of the morphology of the pressure tracing recorded from the ascending aorta, and when calibrated by peripheral blood pressure measurement, it can be used to calculate LV pressure throughout ejection. These pressure estimates can be used to calculate wall stress throughout ejection with a high degree of accuracy.

Adolescent↗

Quantitative radionuclide angiocardiography: detection and quantitation of left to right shunts.

In 105 patients defection and quantitation of left to right shunts was performed using quantitative radionuclide angiocardiography. The radionuclide angiocardiograms were acquired and analyzed by a gamma camera interfaced to a digital computer system. Pulmonary to systemic flow (Qp/As) ratios were calculated by analysis of pulmonary time-activity histograms using a gamma variate model. All patients were studied with cardiac catheterization, left ventricular angiocardiography and radionuclide angiocardiography. The radionuclide method allowed precise detection and quantitation of left to right shunts with a Qp/Qs ratio of 1.2 to 3.0. There was good agreement between the Ap/As ratio calculated by oximetry at cardiac catheterization and radionuclide angiocardiography (r = 0.94). The information gathered with this nontraumatic method appears sufficiently reliable to be used in the management of patients.

Adult↗

Cine magnetic resonance imaging and color Doppler flow mapping in infants and children with pulmonary artery bands.

Cine magnetic resonance imaging (MRI) and color Doppler flow mapping were performed in 12 infants and children (aged 3 to 35 months) after pulmonary artery banding to define the anatomy and physiology of the right ventricular outflow tract and evaluate the anatomy. MRI was performed using a 1.5 Tesla magnet in the sagittal, axial and oblique views with all patients studied in the 24 cm head coli following adequate sedation. High-resolution cine MRI was obtained in all patients and the narrowest flow diameter on cine MRI correlated well with the pressure gradient measured across the band in 11 patients at cardiac catheterization or surgery (r = -0.95). Signal loss was always seen distal to the band associated with turbulent flow as seen by color Doppler flow mapping. Signal loss in cine MRI was also seen proximal to the band. The length of this proximal signal void also correlated well with the pressure gradient measured across the band (r = 0.91) and was closely matched by the zone of proximal spatial acceleration defined by digital computer analysis of color Doppler flow map images (r = 0.89), which also demonstrated low grade variance associated with the laminar accelerating flow stream. The position of the band was accurately defined by cine MRI which identified inadequate pulmonary artery banding in 2 patients confirmed subsequently at cardiac catheterization and angiography. Cine MRI and color Doppler flow mapping when used together provide high-resolution detail about the right ventricular outflow tract and pulmonary artery band anatomy and function.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

Pharmacokinetics of intra-amniotically administered hyperosmolar urea in rhesus monkeys.

Three rhesus monkeys in midgestation were injected intra-amniotically with hyperosmolar 14C-urea (58 per cent weight/volume, 2.3 Gm. per kilogram, 25 muc) and the concentration of 14C-urea measured serially for 24 hours in amniotic fluid, maternal serum, and maternal urine. The volume of the amniotic space was measured by isotope dilution of 99mTc-albumin. The experimental values were fitted to a three-compartment mathematical model with the aid of a digital computer program for nonlinear data. The computer-derived concentration versus time curves were in close agreement with the measured values when the flux of urea was primarily from amniotic fluid to fetal water to maternal water with insignificant direct transport between the amniotic fluid and maternal serum. The half-times for distribution of urea into fetus and mother were approximately 30 minutes and 7 hours, respectively. Thus, although the uptake of urea by the fetus from surrounding amniotic fluid is rapid, the further movement of urea from fetus to mother is relatively slow.

Abortifacient Agents↗

An evaluation of soft-tissue changes resulting from Le Fort I maxillary surgery.

The soft-tissue profile response to maxillary surgery (impaction and advancement) at the Le Fort I level was evaluated. Data were derived from quality-controlled preoperative and postoperative cephalograms of nongrowing patients with their lips in repose. A standardized tracing technique was used, and this was followed by landmark identification and digitization. Computer measurement of the linear distance of each cephalometric point from horizontal and vertical reference lines was then obtained. Soft-tissue change to hard-tissue change ratios, as well as single and multiple regression equations, were calculated from a patient pool representing fourteen impactions and seven advancements. The results demonstrated many statistically significant correlations. The soft-tissue response to maxillary surgery appeared to be predictable, and the anticipated changes following both impaction and advancement surgical procedures were summarized. Prediction schemes for soft-tissue change evaluation were presented and tested, with a mean error value of approximately 22 percent. In addition, the results of this study led to the following abbreviated conclusions: For the impaction group, (1) the upper lip closely followed the movement of the maxillary central incisor in the horizontal plane, (2) the mandibular soft tissue followed the skeletal mandibular autorotation on an approximately 1:1 basis, (3) the lower border of the upper lip moved superiorly approximately 40 percent of the vertical maxillary change, and (4) there was a superior vertical change in all of the maxillary soft-tissue points. For the advancement group, (1) a progressive increase in the horizontal soft-tissue movement from the tip of the nose to the free end of the upper lip was observed and (2) vertical change in the soft-tissue and horizontal movement of the mandibular soft tissue was unpredictable.

Adolescent↗

The increase in vivo by electric currents of the 99mTc-methylene diphosphonate uptake and cyclic AMP content of the bone of the cat mandible.

Technetium-99-methylene diphosphonate (99mTc-MDP) bone images were obtained from live cats whose mandibles had been stimulated non-invasively and unilaterally with electric current (12 +/- 2 microA) for 1 week. The images were obtained using a gamma camera interfaced to a digital computer for quantitative comparison of the mandible. Radionuclide uptake by the stimulated sides increased by 59 +/- 26 per cent when compared with the contralateral control sites. Immunohistochemical staining of mandibular sections for adenosine 3',5'-monophosphate (cyclic AMP) showed that periosteal osteoblasts opposite the electrodes were intensely stained. Thus 99mTc-MDP scintigraphy is a sensitive non-invasive technique for determining in vivo enhanced bone remodelling activity. The immunohistochemistry indicates that the stimulation of bone cells was limited to surfaces adjacent to both cathode and anode.

Animals↗

The relation between tooth eruption and alveolar crest height in a human skeletal sample.

It is commonly assumed that alveolar crest height increases with continuing tooth eruption unless affected by marginal inflammation. To test this hypothesis, the relation between eruption and alveolar crest height was examined in skulls from a sample consisting of the remains of 244 individuals from the late medieval period. The mandibular first and second molars and second premolars were analysed. The age of the skulls was determined on the basis of dental development and molar attrition. Radiographs were taken and points representing the levels of the inferior dental canal (IDC), root apices (AP), alveolar crest (AC), cementum-enamel junction (CEJ) and occlusal surface were determined on the radiographs. The level of the IDC was used as a reference not changing with age. The distances between the points were measured with a help of a computer-digitizer system. Variable IDC-AP increased with age, indicating continuous eruption of the teeth. The distance between AC and CEJ also increased while the distance between IDC and AC remained constant, showing that the alveolar crest height did not increase accordingly. The lack of inflammatory changes on the alveolar bone surface suggests that occlusal attrition may be compensated for by continuous eruption without bone growth in the alveolar margin.

Adolescent↗

The ATPase inhibitor protein in oxidative phosphorylation. The rate-limiting factor to phosphorylation in submitochondrial particles.

1. Purified luciferase and luciferin were used to study the time course of phosphorylation in submitochondrial particles. The light emitted was detected by a single-photon counter, using a multichannel analyser, and the results were analysed by an 'on-line' digital computer. 2. Using NADH as substrate, phosphorylation showed, in general, four phases. These were (i) a period of increasing rate ('lag'); (ii) a period of constant (positive) rate; (iii) a period of zero net rate (plateau), when the phosphorylation potential was maintained at its equilibrium value, and (iv) a period of negative rate (atp hydrolysis) after all the oxygen has been consumed. 3. The lag phase, several seconds in length, was a function of the inhibitor protein content of the particles. It was decreased in particles treated to remove the inhibitor protein, either by prior energisation of the particles with NADH, or by addition of aurovertin, which competes with the inhibitor protein for the ATPase. It was concluded that the ATPase inhibitor inhibits both ATP synthesis and hydrolysis by the ATPase. 4. The rate constant for the release of the inhibitor protein from the energised membrane was determined from the time course of ATP production during the lag phase. The activation energy of this process was measured from the temperature dependence of the lag, and was shown to be 13.3 kcal/mol, lower than the activation energy of ATP synthesis or NADH oxidation. 5. The rate constant for inhibitor release was dependent on 'energisation' of the membrane, being lower in the presence of uncouplers. However, it was possible to decrease the rate constant considerably with agents that collapsed the membrane potential without uncoupling the membrane. It was concluded that the inhibitor protein responded to the membrane potential component of the energisation. 6. A kinetic model for energy-dependent dissociation of the ATPase-inhibitor complex is proposed.

Adenosine Triphosphatases↗

The role of enzyme degradation in enzyme turnover during tissue differentiation.

1. The role of enzyme degradation in enzyme turnover during tissue differentiation has been investigated by the use of equations based on the model of Berlin and Schimke (Mol. Pharmacol. 1 (1965) 149-156). 2. A digital computer has been used to calculate the change in enzyme amounts which would result from different changes in the rates of synthesis and degradation of an enzyme during cell differentiation. The energetics of these alternative processes have been compared. 3. The results demonstrate that changes in the rates of synthesis and degradation of an enzyme after a differentiation stimulus enhance the flexibility and rapidity of changes in enzyme amount during enzyme accumulation. Decreases in the rate of degradation of an enzyme during enzyme accumulation lead to a considerable saving of energy. 4. Hypotheses are proposed to account for the different modes of turnover of protein subgroups during cytodifferentiation in terms of specific changes in the rates of synthesis and degradation of the subgroups.

Cell Differentiation↗

There is less thalamic degeneration in neonatal-lesioned than in adult-lesioned cats after cerebral hemispherectomy.

In order to study age-related processes of degeneration and recovery, the left hemitelencephalon was surgically removed in 5 adult cats and 5 neonatal kittens which were compared to 5 intact controls. After long survival, brains were sectioned in the coronal plane and thionine-stained. Drawings of gross and microscopic thalamic structures were made at 4 planes and computer-digitized to provide 7 measures: total thalamic area at planes A 7.5 and A 8.5; counts of neuroglia, small neurons (31-100 microns2) and large neurons (101-1000 microns2); area of neuroglia, small neurons and large neurons. All cellular measurements were in the ventrobasal complex at planes A 8.0 and A 10.0. Morphological changes were found bilaterally in all lesioned cats. Ipsilateral to the ablation in adult-lesioned cats, thalamic area, large neuron count and glia cells size were markedly and significantly decreased (P less than 0.01), while in neonatal-lesioned cats these changes were present but significantly reduced in magnitude compared to adult-lesioned animals. In addition, adult-lesioned cats showed a marked increase in glial cell numbers (P less than 0.01) and a decrease in small neuron size (P less than 0.01), while kitten-lesioned animals did not show changes in these measures. In the intact side of the brain, the thalamus of adult-lesioned cats was decreased in size (P less than 0.01), and glial cells were decreased in number and size (P less than 0.05), while in kitten-lesioned brains there were few changes. In both lesioned groups large neurons showed a significant increase in size (P less than 0.01). We conclude that neonatal hemispherectomy results in markedly less thalamic atrophy, retrograde neuronal degeneration and gliosis than the equivalent lesion in adults. The changes are discussed in the context of the increased neuroanatomical reorganization and functional recovery which were reported in neonatal- vs adult-lesioned animals.

Aging↗

Localization of binding sites for insulin-like growth factor-I (IGF-I) in the rat brain by quantitative autoradiography.

In vitro quantitative autoradiography was used to localize IGF-I binding sites in rat brain. Slide-mounted sections of frozen rat brain were incubated in 0.01 nM 125I[Thr59]IGF-I, alone or mixed with 10 nM unlabeled [Thr59]IGF-I or insulin, for 22 h at 4 degrees C and apposed to LKB Ultrofilm. Measurement of labeled [Thr59]IGF-I binding by computer digital image analysis of the autoradiographic images indicated that high affinity IGF-I binding sites are widely distributed at discrete anatomical regions of the brain microarchitecture. The highest concentration of specific binding sites was in the choroid plexus of the lateral and third ventricles. Unlabeled porcine insulin was less potent than unlabeled IGF-I in competing for binding sites on brain slices. Regions of the olfactory, visual, and auditory, as well as visceral and somatic sensory systems were labeled, in particular the glomerular layer of the olfactory bulb, the anterior olfactory nucleus, accessory olfactory bulb, primary olfactory cortex, lateral-dorsal geniculate, superior colliculus, medial geniculate, and the spinal trigeminal nucleus. High concentrations of IGF-I-specific binding sites were present throughout the thalamus and the hippocampus, (dentate gyrus, Ca1, Ca2, Ca3). The hypothalamus had moderate binding in the paraventricular, supraoptic, and suprachiasmatic nucleus. Highest binding in the hypothalamus was in the median eminence. The arcuate nucleus showed very low specific binding, approaching the levels found in optic chiasm and white matter regions. Layers II and VI of the cerebral cortex also had moderate IGF-I binding. The results suggest that the development and functions of brain sensory and neuroendocrine pathways may be regulated by IGF-I.

Animals↗

On the separation of semiperiodic superimposed point processes: application to electromyographic signals.

A method for the separation of semiperiodic (Gaussian probability distribution of intervals with moderate coefficient of variation) superimposed point processes, to be implemented on a digital computer is described. The efficiency of the filter used for the extraction of the underlying event sequences from the pooled array has been investigated by simulation. Approximately 80 percent of the events belonging to the underlying sequence to be extracted were recovered (with the addition of "impurity events"), still preserving the mean rate and coefficient of variation of the original indicidual sequence concerned. The program was used on an example of an actual electromyographic recording (comprised of a number of motor units discharging simultaneously), resolving the number of motor units involved, their mean rates, and the coefficient of variation of the individual action potential sequences.

Action Potentials↗

Digital simulation of the membrane voltages and currents in nerve and muscle fibers.

This paper describes digital computer simulations of the membrane voltages and currents in axons and muscle fibers. The simulations, which allow calculations ona nonuniform fiber, are based on the discrete Hodgkin-Huxley and Falk-Fatt equations. An efficient algorithm is used to solve the set of equations generated. Calculations are made of the voltage and current at the natural end of a muscle fiber and the results are compared with measurements by other investigators.

Axons↗

Detection of extracellular action potentials in noise for the control of microelectrode advancement.

A digital computer was programmed to detect impulses in the presence of noise, rather than identify or classify impulse activity from microelectrodes. The analog signal was abstracted into a sequential series of voltage time vectors that measured peak-to-peak activity. The amplitude and time difference between a peak-positive potential and the next peak-negative potential defined one vector. The amplitude and time difference between that negative peak and the next positive peak defined the next vector, and so on. An algorithm determined if each successive vector was part of a signal pattern by comparing the properties of the vector to those in a stored list. The algorithm was designed for future application with minimum computer systems and multiple-tip microelectrodes.

Action Potentials↗