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Biomedical subjects

J Dayan

Publications and source records attributed to J Dayan.

9 recordsLinked to original sources

Control of the cryosurgical process in nonideal materials.

A study of a controlled cryosurgical process is presented. This study is based on the energy equations describing the probe response and the phase change occurring in the medium. First-order nonlinear differential equations (state equations) are obtained by applying the integral-solution method. In order to obtain maximal cell destruction, it is desired to control a specific cooling rate at the solid-liquid interface. This cooling rate defines the desired trajectories of the state variables through the state equations. In order to satisfy the cooling rate condition on the freezing front, a closed-loop is designed to control the probe temperature program. A simple analysis of the system stability employed linearization at several points along the desired trajectories. Ranges of stability were obtained for a system containing a proportional-integral controller. It was demonstrated that these stability ranges depend mainly on the selected sampling time of the discrete control loop and that the phase-change process does not significantly affect the stability results. A complete study of the nonlinear equations was performed by a computer simulation program which enables the selection of the final values of the controller parameters, in order to minimize the error and to ensure stability. In addition, the simulation program gives information about the effects of the A/D and D/A converters accuracy on the performance of the control loop. An A/D converter accuracy of 12 bits was found necessary in order to reduce the oscillations in probe temperature to acceptable values. The simulation also yields a complete calculated temperature field in the tissue during the controlled process. From these simulated results it can be seen that oscillations of +/- 0.5 degrees C in the desired probe temperature do not significantly affect the desired cooling rate at the freezing front. An initial overshoot of 1.5 degrees C in the desired probe temperature was obtained both experimentally and theoretically from the simulation. When this initial overshoot occurs at the beginning of the freezing process, it causes an error in freezing front velocity and consequently in ice-front position. From the numerical simulation, it can be deduced that the cooling rate obtained at the front deviates from the desired value by approximately 1%. The probe-temperature error increases at two instants: a) during the super-cooling effect and the subsequent sudden crystallization, and b) when the probe temperature is below -80 degrees C and unstable boiling of the cooling medium causes oscillations.

Cryosurgery

Controlled freezing of nonideal solutions with application to cryosurgical processes.

Success of a cryosurgical procedure, i.e., maximal cell destruction, requires that the cooling rate be controlled during the freezing process. Standard cryosurgical devices are not usually designed to perform the required controlled process. In this study, a new cryosurgical device was developed which facilitates the achievement of a specified cooling rate during freezing by accurately controlling the probe temperature variation with time. The new device has been experimentally tested by applying it to an aqueous solution of mashed potatoes. The temperature field in the freezing medium, whose thermal properties are similar to those of biological tissue, was measured. The cryoprobe temperature was controlled according to a desired time varying profile which was assumed to maximize necrosis. The tracking accuracy and the stability of the closed loop control system were investigated. It was found that for most of the time the tracking accuracy was excellent and the error between the measured probe temperature and the desired set point is within +/- 0.4 degrees C. However, noticeable deviations from the set point occurred due to the supercooling phenomenon or due to the instability of the liquid nitrogen boiling regime in the cryoprobe. The experimental results were compared to those obtained by a finite elements program and very good agreement was obtained. The deviation between the two data sets seems to be mainly due to errors in positioning of the thermocouple junctions in the medium.

Analog-Digital Conversion

Gender differences in categorizing adolescents' weight status.

Categorization of normal or overweight status, using percent overweight and visual inspection, showed good agreement for 51 adolescent girls, but not 70 boys. Only 49% of boys with high relative weights were seen as overweight compared to 90% of girls.

Adolescent

Stereochemical studies of the pyruvate kinase reaction with (Z)- and (E)-phosphoenol-alpha-ketobutyrate.

(Z)-and (E)-phosphoenol-2-ketobutyrate were synthesized. [3-2H]-2-Ketobutyrates were formed from both isomers in the pyruvate kinase reaction in 2H2O and were converted to chiral propionates. Authentic (2S)-[2-2H]propionic acid was also prepared, and the optical rotatory dispersion curves of the propionates were compared. The rotation compared with standard propionate at 240 nm of sodium (2R)-[2-2H]propionate from the Z isomer was 47% (i.e., 53% was RS), and of (2S)-[2-2H]propionate from the E isomer was 29% (i.e., 71% was RS). Protonation at C-3 of the 2 si, 3 re face of the pseudosubstrates would have yielded (2R)- and (2S)-[2-2H]propionates from the Z and E analogues, respectively. An explanation offered for the nonstereoselective protonation that occurred is dissociation of the enol from the enzyme and subsequent random protonation in solution.

Animals

Yeast mutants deficient in heme biosynthesis and a heme mutant additionally blocked in cyclization of 2,3-oxidosqualene.

Mutants of Saccharomyces cerevisiae were isolated which were blocked in heme biosynthesis and required heme for growth on a nonfermentable carbon source. They were rho+, and grew fermentatively on ergosterol or cholesterol and Tween 80, as a source of oleic acid. Cells grown on ergosterol and Tween 80 lacked cytochromes and catalase which were restored by growth on heme. The mutants comprised five nonoverlapping complementation groups. Tetrad analysis showed that the pleiotropic properties of each of the mutants resulted from a single mutation in one of five unlinked loci (hem1 to hem5) affecting heme biosynthesis. Biochemical studies confirmed that each mutation resulted in loss of a single enzyme activity. hem1 mutants grew on delta-aminolevulinate and lacked delta-aminolevulinate synthase activity, hem2 mutants lacked delta-aminolevulinate dehydratase, and hem3 mutants uroporphyrin I synthase. Mutants in hem1, hem2, and hem3 had an additional requirement for methionine on synthetic medium supplemented with either heme or ergosterol and Tween 80, owing to a lack of sulfite reductase which contains siroheme, a modified uroporphyrin III. Since hem4 and hem5 mutants have sulfite reductase activity under all growth conditions, they are blocked after uroporphyrin III. Cell extracts of a hem4 mutant incubated with delta-aminolevulinate accumulated coproporphyrin III suggesting a block in coproporphyrinogenase, the enzyme which converts coproporphyrinogen III to protoporphyrinogen. Cells and extracts of a hem5 mutant accumulated protoporphyrin IX. Since it was the only mutant that grew on heme but not on protoporphyrin IX, a block in ferrochelatase was suggested for this strain. Mutant strains grown on heme had the sterol composition of wild type cells, whereas without heme only squalene, small amounts of lanosterol, and added sterol was observed. A heme product therefore participates in the transformation of lanosterol to ergosterol. A hem3 mutant was isolated which was also blocked between 2,3-oxidosqualene and lanosterol (erg12). When grown on lanosterol or ergosterol (with Tween 80) it accumulated a compound which was identified as 2,3-oxidosqualene by comparison with the synthetic compound in thin layer and gas-liquid chromatography, and by proton magnetic resonance and mass spectroscopy. Supplementation with heme did not remove the requirement for sterol, but it enabled the mutant to convert lanosterol to ergosterol.

5-Aminolevulinate Synthetase