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At least 217 records · Page 12Linked to original sources

Progression rate of radiation damage to the mouse kidney: a quantitative analysis of experimental data using a simple mathematical model of the nephron.

Mouse kidneys were irradiated bilaterally with a range of single or fractionated X-ray doses. After an interval of 2 weeks or 26 weeks, the animals were reirradiated with a range of single X-ray doses. The rate of development of functional kidney damage was assessed repeatedly by the 51Cr-EDTA clearance assay. The rate at which the damage is expressed was found to depend on the primary dose, on the interval between primary treatment and retreatment, and on the retreatment dose. A subset of the data was analysed using a mathematical model of nephron function. In the model, the residual activity of 51Cr-EDTA depends on the glomerular filtration rate (GFR). The GFR is related to the cellularities of three target cell populations. The filtration capacity of the glomerulus is assumed to depend on the numbers of glomerular endothelial cells and mesangial cells. The reabsorption capacity of the tubule is related to the number of tubular epithelial cells. The impact of tubulo-glomerular feedback and the reserve capacity of the kidney on residual activity is considered. The target cell populations are assumed to be of a flexible type, i.e. to consist of cells which are all both functional and self-renewing. Free parameters of the model were optimized by minimizing the residual sum of squares. With the optimized parameter values, the measured and the model-predicted rates of progression of the functional damage correspond well for a wide range of irradiation schedules. The model analysis suggests a pronounced role of tubulo-glomerular feedback in the development of functional injury in the kidney. It is concluded that the model represents a good starting point for quantitative studies of the cellular basis of radiation nephropathy.

Animals↗

Optimisation of recording conditions for the electron paramagnetic resonance signal used in dental enamel dosimetry.

Optimisation of the parameters for recording the electron paramagnetic resonance (EPR) spectra of dental enamel for absorbed dose reconstruction was performed for an EMX (Bruker) spectrometer supplied with a high-sensitivity microwave cavity. Dose determination was performed using a previously developed automatic spectra processing procedure, which uses the non-linear fit of a model spectrum. The experimental error was estimated as the standard deviation of the results from the nominal doses for the set of spectra recorded for 10 samples prepared from teeth of different persons and irradiated in the dose range 0-500 mGy. The microwave power and magnetic field modulation amplitude corresponding to the minimum of dependencies of the error on these parameters were adopted as the optimal ones. For the sets of spectra recorded at optimal parameters for sample masses 100, 50 and 30 mg, the errors of dose determination were obtained as 18, 27 and 37 mGy respectively.

Adult↗

Effects of internal globus pallidus stimulation on motor cortex excitability.

BACKGROUND: Deep brain stimulation is a promising treatment for PD, but its physiologic effects and mechanisms of action remain poorly understood. Magnetic stimulation studies have revealed abnormalities in several different excitatory and inhibitory circuits in the motor cortex in PD. METHODS: The physiologic effects of internal globus pallidus (GPi) stimulation in seven patients with PD and seven age-matched healthy volunteers were studied. The stimulators were set at the optimal parameters (ON), at half the optimal amplitude (Half-Amp), or switched off (OFF) in random order. Patients were taking their usual medications. Magnetic stimulation was applied to the motor cortex, and motor evoked potentials (MEP) were recorded from the contralateral first dorsal interosseous muscle. Several excitatory and inhibitory pathways that have been found to be abnormal in PD were tested. RESULTS: The motor threshold (MT), MEP recruitment curve (stimulus intensities from 100 to 150% of MT), short and long interval intracortical inhibition, and intracortical facilitation were similar in the three stimulator conditions tested both at rest and during voluntary contraction. The silent period (SP) was longer in the OFF and Half-Amp conditions than in normal control subjects. In the stimulator ON condition, the SP was significantly reduced compared with the OFF condition and became similar to that in normal control subjects. CONCLUSIONS: GPi stimulation while on dopaminergic medications reduced the SP following magnetic stimulation but did not change corticospinal excitability or other measures of intracortical inhibition and facilitation. The reduction of SP may be related to the antidyskinetic and levodopa-blocking effects of ventral GPi stimulation.

Aged↗

Optimization of a polypyrrole glucose oxidase biosensor.

An amperometric glucose biosensor was fabricated by the electrochemical polymerization of pyrrole onto a platinum electrode in the presence of the enzyme glucose oxidase in a KCl solution at a potential of +0.65 V versus SCE. The enzyme was entrapped into the polypyrrole film during the electropolymerization process. Glucose responses were measured by potentiostating the enzyme electrode at a potential of +0.7 V versus SCE in order to oxidize the hydrogen generated by the oxidation of glucose by the enzyme in the presence of oxygen. Experiments were performed to determine the optimal conditions of the polypyrrole glucose oxidase film preparation (pyrrole and glucose oxidase concentrations in the plating solution) and the response to glucose from such electrodes was evaluated as a function of film thickness, pH and temperature. It was found that a concentration of 0.3 M pyrrole in the presence of 65 U/ml of glucose oxidase in 0.01 M KCl were the optimal parameters for the fabrication of the biosensor. The optimal response was obtained for a film thickness of 0.17 microns (75 mC/cm2) at pH 6 and at a temperature of 313 K. The temperature dependence of the amperometric response indicated an activation energy of 41 kJ/mole. The linearity of the enzyme electrode response ranged from 1.0 mM to 7.5 mM glucose and kinetic parameters determined for the optimized biosensors were 33.4 mM for the Km and 7.2 microA for the Imax. It was demonstrated that the internal diffusion of hydrogen peroxide through the polypyrrole layer to the platinum surface was the main limiting factor controlling the magnitude of the response of the biosensor to glucose. The response was directly related to the enzyme loading in the polypyrrole film. The shelf life and the operational stability of the optimized biosensor exceed 500 days and 175 assays, respectively. The substrate specificity of the entrapped glucose oxidase was not altered by the immobilization procedure.

Biosensing Techniques↗

Invited review: biophysical properties and clinical applications of magnetic resonance imaging contrast agents.

Contrast enhanced magnetic resonance imaging (MRI) is a very versatile and effective technique for detecting and characterizing lesions, for identifying a variety of patho-physiological abnormalities, and for providing perfusion and functional information. The application of contrast enhanced MRI to many clinical and research indications has emerged because of the rapid evolution in imaging techniques, improved methodology, and the development of efficient and specific contrast agents. Problems related to optimizing parameters and dosage have been due to complex interplay of relaxation times, biophysical mechanisms and acquisition parameters. A knowledge of basic biophysical aspects is therefore essential for a full understanding of the results obtained for different organs under different conditions, and for optimizing the image parameters and dosage of contrast agents. This article underlines the biophysical basis of the effects of contrast agents in MRI, identifies the problems involved in optimizing the parameters for maximum efficiency, and presents a general overview of the clinical studies and research applications in the central nervous system, perfusion abnormalities, hepatobiliary system, musculoskeletal system and the gastrointestinal tract. The section on perfusion studies includes a discussion of quantitative analysis and kinetic models describing the effects of contrast agents. Finally, a critical evaluation of the scope and limitations of contrast enhanced MRI is presented.

Biophysical Phenomena↗

Variable tip angle slab selection pulses for carotid and cerebral time-of-flight MR angiography. Theory and experimental analysis.

OBJECTIVE: To determine the optimal parameters of variable tip angle slab selection (tilted optimized nonsaturating excitation, TONE) pulses in time-of-flight MR angiography, in order to produce the best visualization of vessels distal to the entry partition. MATERIAL AND METHODS: The influences of the mean flip angle (MFA) and the profile tilt of the TONE pulse in three-dimensional (3D) time-of-flight MR angiography were evaluated with a mathematical modeling of the flow signal amplitude. We compared the calculated flow signals with the signals from flow-phantom models and with those from 6 normal volunteers. 3D gradient echo images (TR/TE 30/7) were acquired with a single variable of the MFA and the profile tilt. The flow velocity of the phantom was maintained at 15 cm/s. Regions of interest were measured on the source images. We also evaluated the visualization of the cerebral vessels on maximum intensity projection images obtained with and without TONE pulses in 5 other healthy volunteers. RESULTS: The changes of flow signals in the phantom and in the volunteers were in good accord with those of the signals mathematically predicted and plotted by a computer, as each parameter was varied. The peripheral saturation was weaker at smaller MFA than at larger MFA. A greater profile tilt produced a more pronounced TONE effect than a lower one. The visualization of the peripheral cerebral vessels was markedly improved by the addition of the TONE pulse. CONCLUSION: Computer simulation is useful for examining the optimal TONE parameters. The TONE pulse markedly improves the visualization of the distal branches of the cerebral vessels.

Adult↗

A dynamic material parameter estimation procedure for soft tissue using a poroelastic finite element model.

A three-dimensional finite element model for a poroelastic medium has been coupled with a least squares parameter estimation method for the purpose of assessing material properties based on intradiscal displacement and reactive forces. Parameter optimization may be based on either load or displacement control experiments. In this paper we present the basis of the finite element model and the parameter estimation process. The method is then applied to a test problem and the computational behavior is discussed. Sequential optimization on different parameter groups was found to have superior convergence properties. Some guidelines for choosing the starting parameter values for optimization were deduced by considering the form of the objective function. For load control experiments, in which displacement data is used for the optimization, the starting values for the elastic modulus should be lower in magnitude than an "anticipated" modulus. The permeability starting values should be higher than an anticipated permeability. For displacement control experiments, the reverse is true. The optimization scheme was also tested on data with random variations.

Anisotropy↗

Short-term control of cardiovascular function: estimation of control parameters in healthy humans.

In a previous study, we recorded short-term cardiovascular responses after a steep increase in arterial pressure in healthy humans [Am. J. Physiol. 266 (Heart Circ. Physiol. 35): H199-H211, 1994]. The aim of the present study was to develop a mathematical model of the baroreflex control of arterial pressure, to use this model with the previously recorded data to estimate unknown parameters in the reflex control loop, and then to analyze the overall open- and closed-loop performance of the system by model simulations with use of individual sets of optimal parameters. The mathematical model consists of a heart, a linear elastic arterial reservoir, and two parallel resistive vascular beds. The arterial baroreflex loop is modeled by two separate time domain processing objects, each with its own gain, time constant, and delay, to simulate the action of a sympathetic signal to the peripheral vascular bed and a parasympathetic signal to the heart. In repeated model simulations, the control parameters in the model were systematically adjusted by an automated algorithm that minimized the deviations between the time courses of the cardiovascular variables simulated by the model and the previously recorded responses in each individual. In all 10 subjects, the short-term cardiovascular responses were adequately simulated by using individual sets of parameters in the model. Open-loop transfer functions for arterial pressure control were obtained by using the individual sets of optimal model parameters in new simulation runs. Open-loop gain for arterial pressure control at nearly zero frequency (steady state) was between 0.9 and 4. Model simulations also indicated an underdampened response at 0.05-0.07 Hz in the closed-loop situation in four subjects, corresponding to peaks in the mean arterial pressor power spectra obtained from separate recordings of spontaneous variations in the resting situation.

Baroreflex↗

Optimization of process parameters for the continuous ethanol production by Kluyveromyces lactis immobilized cells in hydrogel copolymer carrier.

In the present study the optimized parameters for highest ethanol productivity by Kluyveromyces lactis immobilized cells bioreactor were obtained using the method of Lagrange multipliers. Immobilized growing yeast cells in PVA: HEMA (7%: 10%, w/w) hydrogel copolymer carrier produced by radiation polymerization were used in a packed-bed column reactor for the continuous production of ethanol from lactose at different levels of concentrations (50, 100 and 150) gL(-1). The results indicate that volumetric ethanol productivity is influenced by substrate concentration and dilution rate. The highest value 7.17 gL(-1) h(-1) is obtained at higher lactose concentration (150 gL(-1)) in feed medium and 0.3 h(-1) dilution rate. The same results have been obtained through the application of "LINGO" software for mathematical optimization.

Cells, Immobilized↗

Multiple peptide fraction collection by capillary electrophoresis with reinjection analysis.

This papers addresses many of the optimization parameters necessary to convert from high resolution capillary electrophoresis (CE) analytical separation parameters to automated, micropreparative multiple fraction collection using software-controlled, interrupted applied voltage. Optimization of two parameters are crucial: 1) preparative sample loading and 2) the determination of peak collection windows. Factors affecting sample loading volume are discussed, such as capillary inner diameters, sample temperatures and sample injection times. Peak collection windows have been determined experimentally and offer an advantage to windows calculated using a linear mobility relationship, especially for long run times, high current levels, and multiple voltage ramping required for multiple fraction collection. Reinjection analysis of both non-glycopeptides and glycopeptides are examined, and clearly indicate peak mobility can be employed for identifying the collected peptides. Difficulties associated with quantitation of the collected peaks by CE are described and appear to be predominantly associated with sample matrix effects.

Buffers↗

Evaluation of liquid handling conditions in microplates.

Liquid handling in higher density microplates (e.g., 1536-well microplates) for more efficient drug screening necessitates carefully selected and optimized parameters. The quality of a liquid handling procedure is dependent on the carryover rate of residual liquids during the pipetting process, the mixing behavior in the wells, foam and bubble formation, and evaporation. We compared and optimized these parameters in 96-, 384-, and 1536-well microplates, and herein we critically evaluate the performance of the CyBi-Well 96/384/1536 automated micropipetting device, which formed the basis of our evaluation studies.

Drug Contamination↗

Optimization of scanning parameters for CT colonography.

To determine the optimal collimation, pitch and reconstruction interval for CT colonography, 10 spherical polyps between 1 mm and 10 mm diameter and made of tissue equivalent material with a CT number of 40 Hounsfield units (HU) were placed in the colon of an anthropomorphic phantom. The phantom was scanned at slice thicknesses of 3 mm, 5 mm and 7 mm and pitches of 1.0, 1.3, 1.5, 1.7 and 2.0 on an IGE Hispeed advantage system. Images were reconstructed for each scanning parameter at the minimum intervals allowed along the z-axis. The optimum scanning protocol was assessed by measuring maximum contrast between the polyp and air, sensitivity for detection of each polyp along the z-axis, and relative radiation dose. In addition, images were reviewed separately by two radiologists who graded polyp conspicuity as: 0, not seen; 1, faintly seen; 2, well seen. It was found that varying the scanning parameters caused a marked alteration in the maximum contrast between each polyp and air. For example, for the 5 mm polyp, the range of contrasts from best to worst case was 910-490 HU. It was noted that with contrasts of less than 500 HU, polyps were only faintly seen. A slice thickness of 3 mm with a pitch of 2 offers optimal polyp conspicuity with a relatively low radiation dose, we conclude that scanning parameters can be optimized for threshold contrast, radiation dose and subjective conspicuity. We propose an optimal parameter of 3 mm slice thickness and pitch 2.

Anthropometry↗

Systematic optimization of expression and refolding of the Plasmodium falciparum cysteine protease falcipain-2.

The Plasmodium falciparum cysteine protease falcipain-2 is a potential new target for antimalarial chemotherapy. In order to obtain large quantities of active falcipain-2 for biochemical and structural analysis, a systematic assessment of optimal parameters for the expression and refolding of the protease was carried out. High-yield expression was achieved using M15(pREP4) Escherichia coli transformed with the pQE-30 plasmid containing a truncated profalcipain-2 construct. Recombinant falcipain-2 was expressed as inclusion bodies, solubilized, and purified by nickel affinity chromatography. A systematic approach was then used to optimize refolding parameters. This approach utilized 100-fold dilutions of reduced and denatured falcipain-2 into 203 different buffers in a microtiter plate format. Refolding efficiency varied markedly. Optimal refolding was obtained in an alkaline buffer containing glycerol or sucrose and equal concentrations of reduced and oxidized glutathione. After optimization of the expression and refolding protocols and additional purification with anion-exchange chromatography, 12 mg of falcipain-2 was obtained from 5 liters of E. coli, and crystals of the protease were grown. The systematic approach described here allowed the rapid evaluation of a large number of expression and refolding conditions and provided milligram quantities of recombinant falcipain-2.

Animals↗

Screening for 2-acetyl-1-pyrroline in the headspace of rice using SPME/GC-MS.

Solid phase microextraction (SPME) is used to collect and concentrate the compounds in the headspace of rice. This research describes optimization parameters of temperature, moisture, and sampling time. Optimization was based upon the recovered levels of 2-acetyl-1-pyrroline (2-AP), the popcorn aroma in aromatic rice. The method uses a sampling temperature of 80 degrees C and adds 100 microL of water to a 0.75 g sample of rice. The rice was preheated for 25 min, a carboxen/DVB/PDMS SPME fiber was exposed to the headspace for 15 min, and a subsequent GC-MS analysis took 35 min. Samples of rice can be analyzed as the flour, milled kernels, or brown rice. Twenty-one experimental rice varieties were analyzed by the SPME method and compared to a wet technique. Recoveries of several nanograms of 2-AP from 0.75 g samples of aromatic rice were observed, whereas only trace amounts of 2-AP were recovered from nonaromatic rice. Recovery from a single SPME headspace analysis is calculated to be 0.3% of the total 2-AP in the sample.

Gas Chromatography-Mass Spectrometry↗

Ab initio and molecular mechanics (MM3) calculations of protonated-neutral diamine hydrogen bonds.

Ab initio calculations of cation-neutral diamine complexes have been carried out at the MP2/6-311+G** level. The geometry and energetics of the charge-reinforced hydrogen bond are analyzed with respect to the alkyl substitution of both the protonated and neutral nitrogen atoms, and these results have been used to improve the quality of the MM3(2000) force field. In addition, specialized hydrogen bond parameters optimized for MM3(2000) are presented. These parameters allow very accurate gas-phase modeling of the charge-neutral diamine environment. Molecular mechanics calculations can model effectively protonated amine-neutral amine hydrogen bonds in the gas phase and solution (continuum dielectric) through a combination of charge-dipole interactions and explicit hydrogen-bonding terms.

Diamines↗

Basis for optimization of in vitro exposure apparatus for health hazard evaluations of mobile communications.

The main objective of this paper is to carefully study the fields induced in flasks exposed to RF electromagnetic fields. The study focuses on the widely used 60 mm Petri dishes and rectangular T-75 flasks for the two following cases: 1) cells in homogeneous suspension and 2) cell monolayers. The dependence of the coupling and the homogeneity of the SAR distribution on frequency (0.7 GHz to 2.5 GHz), polarization (E, H and k polarizations) and the amount of medium (1.9 mm to 4.7 mm medium height) is studied. In addition, the effects of the environment, meniscus and field impedance as well as the distortion of the incident field are discussed. Based on these results, advantages and disadvantages of different fundamental designs of apparatus used in the past are compared. These are TEM cells, HF chambers, radial transmission lines (RTL), waveguides and wire patch cells. Furthermore, the major optimization parameters are identified for the development of highly optimized exposure systems, enabling the conduct of high quality experiments.

Biophysical Phenomena↗

Application of modified Rosenbrock's method for optimization of nutrient media used in microorganism culturing.

The Rosenbrock's procedure has been modified for optimization of nutrient medium composition and has been found to be less tedious than the Box-Wilson method, especially for larger numbers of optimized parameters. Its merits are particularly obvious with multiparameter optimization where the gradient method, so far the only one employed in microbiology from a variety of optimization methods (e.g., refs, 9 and 10), becomes impractical because of the excessive number of experiments required. The method suggested is also more stable during optimization than the gradient methods which are very sensitive to the selection of steps in the direction of the gradient and may thus easily shoot out of the optimized region. It is also anticipated that other direct search methods, particularly simplex design, may be easily adapted for optimization of medium composition. It is obvious that direct search methods may find an application in process improvement in antibiotic and related industries.

Culture Media↗

Optimization of the immobilization parameters and operational stability of immobilized hydantoinase and l-N-carbamoylase from Arthrobacter aurescens for the production of optically pure l-amino acids.

2The immobilization parameters were optimized for the hydantoinase and the L-N-carbamoylase from Arthrobacter aurescens DSM 3747 or 3745, respectively. To optimize activity yields and specific activities for the immobilization to Eupergit C, Eupergit C 250 L, and EAH-Sepharose wild-type, recombinant and genetically modified ('tagged') enzymes were investigated concerning the influence of the protein concentration, the kind of support and the immobilization method. For both enzymes, the use of the recombinant proteins resulted in enhanced specific activities especially when using a hydrophilic support for immobilization such as Sepharose. In the case of a genetically modified hydantoinase carrying a His(6)-tag, affinity coupling led to a loss of activity of higher than 80%. Both enzymes were significantly stabilized by immobilization: In packed bed reactors, Eupergit C 250 L (NH(2))-immobilized hydantoinase and EAH-Sepharose-immobilized L-N-carbamoylase showed half-life times of approx. 14000 and 900 hours, respectively. Together with specific activities of the immobilized enzymes of 2.5 U/g wet carrier (hydantoinase) and 10 U/g wet carrier (L-N-carbamoylase) the newly developed biocatalysts are sufficient to fulfill industrial requirements.In comparison to the free enzymes, temperature and pH-optima were increased by 10 degrees C and one pH unit, respectively, after immobilization. The pH and temperature optima of the hydantoinase (L-N-carbamoylase) were determined to be pH 8.5-10 (pH 9.5) and 45-60 degrees C (60 degrees C).In order to provide sufficient amounts of biocatalyst for the process development in mini plant scale, a 50 fold scale-up of the optimized immobilization procedure was carried out for both enzymes. Because of the overlapping optima, both immobilized enzymes can be operated together in one reactor.

Journal Article↗