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Biomedical subjects

R C Simpson

Publications and source records attributed to R C Simpson.

At least 19 recordsLinked to original sources

The NavChair Assistive Wheelchair Navigation System.

The NavChair Assistive Wheelchair Navigation System [19] is being developed to reduce the cognitive and physical requirements of operating a power wheelchair for people with wide ranging impairments that limit their access to powered mobility. The NavChair is based on a commercial wheelchair system with the addition of a DOS-based computer system, ultrasonic sensors, and an interface module interposed between the joystick and power module of the wheelchair. The obstacle avoidance routines used by the NavChair in conjunction with the ultrasonic sensors are modifications of methods originally used in mobile robotics research. The NavChair currently employs three operating modes: general obstacle avoidance, door passage, and automatic wall following. Results from performance testing of these three operating modes demonstrate their functionality. In additional to advancing the technology of smart wheelchairs, the NavChair has application to the development and testing of "shared control" systems where a human and machine share control of a system and the machine can automatically adapt to human behaviors.

Algorithms↗

Automatic adaptation in the NavChair Assistive Wheelchair Navigation System.

The NavChair Assistive Wheelchair Navigation System [7] is an adaptive shared control system being developed to provide mobility to those individuals who would otherwise find it difficult or impossible to use a power wheelchair due to cognitive, perceptual, or motor impairments. The NavChair provides task-specific navigation assistance to the wheelchair operator in the form of several distinct operating modes, each of which distributes control differently between the wheelchair and the operator. This paper describes the NavChair's mechanism for automatically selecting the most appropriate operating mode based on a combination of the wheelchair's immediate situation and its global location. Results from two experimental evaluations of the adaptation method are presented.

Adult↗

Adaptive one-switch row-column scanning.

Row-column scanning is a very slow method of communication. Options for increasing text entry rate include 1) dynamically changing the configuration of the row-column matrix or 2) using rate-enhancement techniques like word prediction, but evidence suggests that increased cognitive load imposed by these methods on the user can result in little or no improvement in text generation rate. An alternative we are investigating is adapting a system's scan delay during run-time. Our goal is to allow a scanning system to adjust its parameters "on the fly" (as opposed to the current practice of setting parameters during clinical assessments). This paper describes the evolution of a one-switch row-column scanning system that adapts its scan rate based on measurements of user performance. Two experiments have been performed to explore the effects of automatically adapting scan delay on users' text entry rate. Our results indicate that automatic adaptation has the potential to enhance text-entry rate without increasing task complexity.

Adult↗

Determination of oxiracetam in human plasma by reversed-phase high-performance liquid chromatography with fluorimetric detection.

Reversed-phase HPLC methodology utilizing pre-column derivatization and post-column reaction fluorimetric detection has been developed and applied to the determination of oxiracetam in human plasma. The method involves preliminary isolation of oxiracetam and internal standard from plasma by solid-phase extraction prior to the formation of their n-propyl carbamate derivatives. The carbamate derivatives were subsequently isolated by solid-phase extraction and subjected to a gradient liquid chromatographic separation on an octadecylsilica column prior to on-line post-column alkaline hydrolysis to produce the corresponding primary amine, which was in turn derivatized with o-phthalaldehyde and 3-mercaptopropionic acid to yield a fluorescent isoindole. The isoindole was then quantified using a fluorescence detector. The method provided an on-column detection limit of 0.5 ng of oxiracetam and was sufficiently sensitive, accurate, and precise to support pre-clinical or clinical pharmacokinetic studies.

Chromatography, High Pressure Liquid↗

High-performance liquid chromatography-time-of-flight mass spectrometry and its application to peptide analyses.

High-performance liquid chromatography (HPLC) has been successfully interfaced on-line with liquid secondary-ion time-of-flight mass spectrometry, utilizing a continuous-flow interface. Time-of-flight mass spectrometry (TOF-MS) is a low-resolution, high-mass-range technique, compatible with extremely rapid data acquisition rates. Thus a TOF-MS system is extremely well suited for coupling with HPLC. This paper describes the interface used to couple the HPLC and TOF-MS as well as the basic operating principles of such a system. Using both standard and packed-capillary reversed-phase HPLC columns, the HPLC-TOF-MS system has been successfully used to separate and detect peptides, providing molecular weight information for the peptide analytes. Experimental data, including chromatograms (UV, reconstructed ion and selected ion) and mass spectra, are presented to demonstrate the ability of the HPLC-liquid secondary-ion TOF-MS system to resolve chromatographically analytes as well as to resolve mass spectrometrically analytes which are unresolved on the chromatographic column.

Chromatography, High Pressure Liquid↗

Adaptation of a thermospray liquid chromatography/mass spectrometry interface for use with alkaline anion exchange liquid chromatography of carbohydrates.

An interface is described that allows the direct coupling of high-performance alkaline anion exchange liquid chromatography with thermospray mass spectrometry. A membrane suppressor is used to remove nonvolatile alkaline salts from the mobile phase after the chromatographic process is completed and prior to introduction into the mass spectrometer. Examples are given of both isocratic and gradient separations of a three-component test mixture of N-acetylated mono- and disaccharides, followed by on-line mass spectral data acquisition. Sensitivity studies show minimum detection limits for the test compounds to be in the microgram range.

Carbohydrates↗

Fast, microbore, and fast microbore high-performance liquid chromatography of nucleic acid constituents.

Fast high-performance liquid chromatography (HPLC) (5-10 cm X 4.6 mm I.D. columns), microbore HPLC (25 cm X 2.1 mm and 1 mm I.D. columns), and fast microbore HPLC (5-10 cm X 2.1 mm and 1 mm I.D. columns) were successfully applied to the separation of nucleic acid constituents in standard mixtures and physiological fluids. Separations were obtained in isocratic and gradient elution modes. The separations obtained were compared with those achieved on a conventional 25 cm X 4.6 mm I.D. column. Factors evaluated included separation time, retention time reproducibility, peak height reproducibility, resolution, efficiency, sensitivity and linear response range. Practical factors, such as the amount of sample required and cost per analysis, were also examined.

Chromatography, High Pressure Liquid↗

Development of a microbore high-performance liquid chromatographic system for biological applications.

Simple and relatively inexpensive modifications are described for conversion of an existing high-performance liquid chromatographic system to a microbore system capable of isocratic or gradient elution. Use of micro guard columns was shown to be a practical method of protecting the microbore analytical columns when chromatographing samples of physiological origin. The microbore chromatograph was successfully integrated with an autoinjector to permit automation of the system. The modified microbore system was used successfully for the isocratic and gradient separations of standard solutions as well as physiological samples. Evaluation of the system performance was based upon comparisons of column efficiency, selectivity, resolution, and sensitivity.

Blood Chemical Analysis↗

High-performance liquid chromatographic profiling of nucleic acid components in physiological samples.

The papers reviewed represent recent progress in HPLC profiling of nucleic acid components in physiological samples. Each method was designed for a particular application and possesses certain inherent advantages and/or disadvantages. Many methods are simply modifications of previous procedures. Although some methodologies appear to be superior to others, there is no "best" method for universal usage. The analyst must use the procedure which is best suited for the particular application at hand. This review is meant to be a starting point for the chromatographer who is comparing and evaluating HPLC methods for a given application.

Animals↗

Evaluation of HPLC column performance for clinical studies.

Several C18 HPLC columns, varying in column length as well as packing material diameter, were used to separate mixtures of biochemical compounds in standards and in various physiological fluids. The column performances were compared both qualitatively and quantitatively. Factors investigated included efficiency, resolution, selectivity, column effect on peak height, temperature effects, cost per analysis, and analysis times. Column lifetime was also examined. The results were used to evaluate the suitability of the various columns for use in the chromatographic analysis of physiological samples.

Blood Chemical Analysis↗

Effects of dietary protein and fat sources on plasma cholesterol parameters, LCAT activity and amino acid levels and on tissue lipid content of growing pigs.

Young male pigs were used to examine effects of dietary protein and fat sources on plasma cholesterol parameters. Diets providing 16 and 42% of metabolizable energy from protein and fat, respectively, were fed for 12-14 weeks. Protein was derived either from plant sources (50% from soybean meal and 25% each from corn and wheat) or from animal sources (90% from casein and 10% from lactalbumin). The polyunsaturated to saturated fat ratio in the diets averaged 3.0 in the polyunsaturated fat diets and 0.3 in the saturated fat diets. Cholesterol content of the four experimental diets (plant protein-polyunsatured fat; plant protein-saturated fat; animal protein-polyunsaturated fat; and animal protein-saturated fat) was 0.6 mg/kcal. Consumption of diets containing plant protein rather than animal protein reduced total plasma cholesterol levels by 50 mg/dl; high density lipoprotein (HDL) cholesterol levels were also lowered in pigs fed plant protein. Similarly, plasma cholesterol levels were approximately 40 mg/dl lower in pigs fed the polyunsaturated fat diets than in pigs fed the saturated fat diets. HDL cholesterol levels, however, were unaffected by source of fat fed. These results show that the hypocholesterolemic action of the plant proteins was as great as the hypocholesterolemic action of polyunsaturated fat and that consumption of plant proteins rather than animal proteins resulted in lower plasma cholesterol levels regardless of whether polyunsaturated or saturated fats were fed.

Amino Acids↗

Purification of dihydropterin reductase using immobilized Cibacron Blue.

Chromatography on columns of immobilized Cibacron Blue (Blue Dextran--agarose) can be used as a major step in the purification of quinonoid dihydropterin reductase. The reductase has been isolated from fractions of beef kidney by selective binding to the immobilized Cibacron in the presence of tetrahydropterin. The binding of the reductase to Blue Dextran and its specific elution from columns of Blue Dextran--agarose indicate that the reductase possesses the dinucleotide (NAD+) binding domain. The results of kinetic experiments give validity to both our affinity chromatography of the reductase and to an ordered mechanism for the formation of tetrahydropterin. Chromatography on Blue Dextran--agarose has been used to show that folate or amethopterin can compete with Cibacron Blue for the dinucleotide domain of the reductase. The p-aminobenzoyl-glutamate moiety of the folates competes with Cibacron Blue for the NADH site of the reductase. A stable binary complex of dihydropterin reductase with NADH has been detected by gel electrophoresis.

Anthracenes↗

The isolation and identification of 2-methyl-2,4-thiazolidine dicarboxylate as a by-product in the conversion of cysteine to glucose in the perfused rat liver.

Cysteine is one of the more toxic amino acids, however the toxic agent associated with cysteine toxicity has not been identified. Recently it was shown that 2-methyl-2,4-thiazolidine dicarboxylate (MTD) was formed fromcy steine by rat liver and would be toxic to the rat. This suggested that MTD formed by the rat liver can be produced both enzymatically and by chemical interaction between cysteine and another compound, possibly pyruvate. When MTD (1 mmol/rat) was injected into 6 rats, two of them died. Only 70-80% of the MTD was excreted within 24 h, suggesting an accumulation of MTD. It is possible the MTD could accumulate in the tissues until it reached a toxic concentration. Whether this could account for the death associated with cysteine toxicity is unknown.

Animals↗

Fractors affecting the rate of gluconeogenesis from L-cysteine in the perfused rat liver.

It has been shown that the net rate of gluconeogenesis from cysteine was only 10% the rate observed from pyruvate. This suggested that the rate limiting step in gluconeogenesis from cysteine was between cysteine and pyruvate. Evidence is presented showing that the cysteine-sulfinate pathway does not play a regulating role in the conversion of cysteine to glucose. Thus, liver cysteine desulfhydrase (CDS) activity and hydrogen sulfide production were evaluated for their potential effects. Liver CDS activity was increased by a 3 day starvation, by feeding a 90% casein diet or a 4% cysteine + 86% casein diet. In all cases the activity of the enzyme was in excess of that required to account for the rate of conversion of cysteine to glucose observed, thus the potential activity of this enzyme was not a rate limiting factor. The possible effect of H2S, an end product of the CDS reaction, on gluconeogenesis from cysteine was evaluated. The addition of NaHS abolished the glucogenic response observed from cysteine, but had very little effect on glucoeogenesis from lactate, suggesting that accumulated H2S may inhibit CDS, marking CDS rate limiting in the conversion of cysteine to pyruvate.

Animals↗

Relative importance of the two major pathways for the conversion of cysteine to glucose in the perfused rat liver.

The effects of dietary treatments and substrate availability on the rate of gluconeogenesis from L-cysteine has been investigated in the perfused rat liver. At an optimal concentration (10 mM) of [U-14C]cysteine, after 40 minutes, 3.9% of the label appeared in glucose. This corresponded to 90% of the net glucose coming from cysteine. Cysteine was then shown to be converted to glucose at a physiological concentration of substrate (0.1 mM) as well as at the optimal concentration. After 40 minutes of perfusion with 0.1 mM [U-14C]cysteine as the substrate, livers of 72-hour starved rats incorporated 1.7% of the label into glucose, and livers of rats perfused without prior starvation incorporated 0.53% of the label into glucose. This suggested that cysteine was glucogenic at optimal and physiological concentrations of cysteine in both fed and starved rats. To determine which, if either, of the two suggested pathways for the conversion of cysteine to glucose was quantitatively more important, livers were perfused with [U-14C]cysteine alone or with [U-14C]cysteine plus cysteine sulfinic acid. The addition of cysteine sulfinate (10 mM) reduced the incorporation of 14C from cysteine into glucose from 3.9 to 2.7%. This suggested that one-third of the cysteine to glucose proceeded via the cysteine sulfinate-dependent pathway.

Animals↗

Gluconeogenesis from L-cysteine in the perfused rat liver.

The effects of dietary and hormonal treatments on the rate of gluconeogenesis from L-cysteine have been investigated in the perfused rat liver in situ. In order to demonstrate gluconeogenesis from L-cysteine, rats were fed either a 90% casein diet, or this diet with 2 or 4% cysteine, added in place of casein, and perfused in the fed state; or fed stock diet and starved 48 or 72 hours; or fasted and injected with cortisol. The net rate of gluconeogenesis (in mumoles/min/g liver) from cysteine in rats fed 4%cysteine was 0.24; in 48-hour starved rats it was 0.10; in 72-hour starved rats it was 0.16; and in the cortisol injected rats it was 0.23. When [U-14C]cysteine plus carrier cysteine (10 mM) was added as the substrate for gluconeogenesis in 72-hour starved rats; 3.9% of the label appeared in glucose. The above dietary and hormonal treatments stimulated gluconeogenesis from L-cysteine.

Animal Nutritional Physiological Phenomena↗